PMID- 17841637 TI - DEMONSTRATIONS WITH THE MUSICAL ARC. PMID- 17841638 TI - THE "ROCK WALL" OF ROCKWALL, TEXAS. PMID- 17841639 TI - APOGAMY IN OEligNOTHERA. PMID- 17841641 TI - TIMBERLINES AS INDICATORS OF CLIMATIC TRENDS. PMID- 17841640 TI - MEMBRANE FORMATION AND PIGMENT MIGRATION IN SEA URCHIN EGGS AS BEARING ON THE PROBLEM OF ARTIFICIAL PARTHENOGENESIS. PMID- 17841642 TI - SURVIVAL OF MARMOTS AFTER NEPHRECTOMY AND ADRENALECTOMY. PMID- 17841644 TI - THE SIXTH EDITION OF THE BIOGRAPHICAL DIRECTORY OF AMERICAN MEN OF SCIENCE. PMID- 17841643 TI - THE BLACK WIDOW SPIDER IN VIRGINIA. PMID- 17841645 TI - THE ADSORPTION-ABSORPTION AND TRANSLOCATION OF DERRIS CONSTITUENTS IN BEAN PLANTS. PMID- 17841647 TI - RELATION OF CERTAIN VIRUSES TO THE ACTIVE AGENT OF THE ROUS CHICKEN SARCOMA. PMID- 17841646 TI - A RECENTLY ISOLATED STRAIN OF POLIOMYELITIC VIRUS. PMID- 17841648 TI - INFLUENCE OF DEUTERIUM OXIDE ON PHOTOCHEMICAL AND DARK REACTIONS OF PHOTOSYNTHESIS. PMID- 17841649 TI - A SIMPLE METHOD OF MEASURING ROTATIONAL SPEEDS. PMID- 17841651 TI - INAUGURAL ADDRESS OF PRESIDENT BUTLER, OF COLUMBIA UNIVERSITY. PMID- 17841650 TI - INSTRUMENT TENTS. PMID- 17841653 TI - SPRING MEETING OF THE COUNCIL OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17841652 TI - TYPES AND SYNONYMS. PMID- 17841654 TI - CENTRAL CONTROL OF THE EXPERIMENTAL STATIONS. PMID- 17841656 TI - SECTION D, MECHANICAL SCIENCE AND ENGINEERING OF THE AMERICAN ASSOCIATION. PMID- 17841655 TI - SECTION A, MATHEMATICS AND ASTRONOMY. PMID- 17841657 TI - THE SUBMARINE VALLEYS OF THE CALIFORNIA COAST. PMID- 17841659 TI - RECENT PROGRESS IN PETROLOGY. PMID- 17841658 TI - PRELIMINARY OBSERVATIONS ON A SUBDERMAL MITE OCCURRING AMONG THE BIRDS IN THE NEW YORK ZOOLOGICAL PARK. PMID- 17841660 TI - THE ALASKA FUEL SUPPLY. PMID- 17841662 TI - NSF Appointments. PMID- 17841661 TI - Extraterrestrial intelligence: a skeptical view of radio searches. PMID- 17841663 TI - Protectionism and the universities. PMID- 17841664 TI - Cosmic-ray record in solar system matter. AB - The energetic nuclei in cosmic rays interact with meteoroids, the moon, planets, and other solar system matter. The nuclides and heavy nuclei tracks produced by the cosmic-ray particles in these targets contain a wealth of information about the history of the objects and temporal and spatial variations in the particle fluxes. Most lunar samples and meny meteorites have complex histories of cosmicray exposure from erosion, gardening, fragmentation, orbital changes, and other processes. There appear to be variations in the past fluxes of solar particles, and possibly also galactic cosmic rays, on time scales of 10(4) to 10(7) years. PMID- 17841666 TI - Congress Ducks the MX. PMID- 17841665 TI - Ethiopia halts prehistory research. PMID- 17841667 TI - Princeton physicists meet tokamak deadline. PMID- 17841669 TI - Compact fusion: small is beautiful. PMID- 17841668 TI - A "euro-brookings" enters the lists. PMID- 17841670 TI - El chichon climate effect estimated. PMID- 17841671 TI - 1982 election results. PMID- 17841672 TI - SOHIO Grant Funds Major Science Education Initiative. PMID- 17841676 TI - AAAS--Newcomb Cleveland Prize Announced. PMID- 17841673 TI - Proposals and resolutions invited for 1983 council meeting. PMID- 17841677 TI - International committee plans future actions. PMID- 17841678 TI - R & d colloquium slated for march. PMID- 17841679 TI - A theory of economic change. PMID- 17841680 TI - A wartime effort. PMID- 17841681 TI - The storage battery. PMID- 17841682 TI - Botanical history. PMID- 17841683 TI - Evolution of an orogenic belt. PMID- 17841684 TI - Temperature and precipitation estimates through the last glacial cycle from clear lake, california, pollen data. AB - Modern pollen surface samples from six lake and marsh sites in the northern California Coast Ranges establish a linear relation between elevation and the oakl(oak + pine) pollen ratio. Modern temperature and precipitation lapse rates were used to convert variations in the pollen ratio into temperature and precipitation changes. Pollen data from two cores from Clear Lake, Lake County, California, spanning the past 40,000 and 130,000 years were used to estimate temperature and precipitation changes through the last full glacial cycle. The maximum glacial cooling is estimated to be 7 degrees to 8 degrees C; the last full interglacial period was about 1.5 degrees C warmer than the Holocene, and a mid-Holocene interval was warmer than the present. The estimated precipitation changes are probably less reliable than the estimated temperature changes. PMID- 17841685 TI - Neutron-induced fission of uranium: a dating method for lunar surface material. AB - Volcanic glasses collected on the rim of Shorty Crater in the Apollo 17 area were formed 3.63 x 10(9) years ago. The amounts of xenon-136 produced by neutron induced fission of uranium-235 indicate that the glasses resided on the lunar surface for about 38 million years before they were deeply buried. The glass spherules were reexcavated by the impact that formed Shorty Crater 17 million years ago, and remained undisturbed until they were collected. PMID- 17841686 TI - Crystalline todorokite associated with biogenic debris in manganese nodules. AB - Platy intergrowths of crystalline todorokite are associated with biogenic debris in the cores of manganese nodules from a site in the Pacific Ocean. Analyses by electron diffraction and transmission electron microscopy demonstrate that this material is composed of tunnels of chains of linked MnO(6) octahedra. The chemical composition, morphology, and stability of the todorokite differ from those of nickel-and copper-rich manganese oxides in nodules that have been identified as todorokite or buserite in earlier investigations. PMID- 17841687 TI - Spider web protection through visual advertisement: role of the stabilimentum. AB - The conspicuous white silken adornments known as stabilimenta, which are commonly found in the orb webs of some spiders, appear to be protective devices that warn birds of the presence of webs in their flight path. Webs endowed with artificial equivalents of stabilimenta tended to survive intact the early morning period when birds are on the wing; unmarked webs showed a high incidence of destruction. PMID- 17841688 TI - Adaptation of fruit morphology to dispersal agents in a neotropical forest. AB - Two-thirds of 258 fruit species from Peruvian tropical forest belong to one of two classes: large orange, yellow, brown, or green fruits with a husk; or small red, black, white, blue, purple, or mixed-color fruits without a husk. The characteristics of the two fruit classes match the size, visual ability, and jaw morphology of mammals and birds, respectively, and the animals also prefer to eat one class of fruits. Thus, most plants in this forest seem to be adapted to seed dispersal by either of two distinct broad arrays of animal taxa. PMID- 17841690 TI - PRODUCTS and MATERIALS. PMID- 17841689 TI - Synchronized moulting controlled by communication in group-living collembola. AB - Group-living Collembola of the genus Hypogastrura coordinate their moulting by communication. Animals of different ages and moulting rhythms synchronized the moulting rhythms when combined in a single culture. This synchronization is apparently not dependent on external stimuli but is coordinated by chemical communication among these insects. PMID- 17841691 TI - This week in science. PMID- 17841692 TI - ESA's Planetary Program. PMID- 17841693 TI - Fluorescent tagging. PMID- 17841694 TI - Women in science. PMID- 17841695 TI - Women in science. PMID- 17841696 TI - Women in science. PMID- 17841697 TI - Corrections and clarifications. AB - In the report "Homozygous human TAP peptide transporter mutation in HLA class I deficiency" by H. de la Salle et al. (8 July, p. 237), figure 2B (p. 239) was printed incorrectly. The correct figure appears below. PMID- 17841699 TI - Sciencescope. PMID- 17841698 TI - First up and out. PMID- 17841701 TI - Leo esaki: an outsider brings a culture change to tsukuba. PMID- 17841700 TI - Magnetic fusion tops limit at princeton. PMID- 17841702 TI - Coaxing light from single atoms. PMID- 17841704 TI - Productive work for tobacco. PMID- 17841703 TI - Element 110 is created, but who spotted it first? PMID- 17841705 TI - Less hot air from Indian rice. PMID- 17841707 TI - Sperm factories. PMID- 17841706 TI - African-american longevity. PMID- 17841709 TI - Madness and creativity revisited. PMID- 17841708 TI - Anatomy On-line. PMID- 17841710 TI - Superconductivity: a third route? PMID- 17841711 TI - Can a magnetic field induce absolute asymmetric synthesis? PMID- 17841712 TI - Signaling the arrest of pollen tube development in self-incompatible plants. AB - Self-incompatibility (SI), the cellular recognition system that limits inbreeding, has served as a paradigm for the study of cell-to-cell communication in plants since the phenomenon was first described by Darwin. Recent studies indicate that SI is achieved by diverse molecular mechanisms in different plant species. In the mustard family, the mechanism of SI shows parallels to the signaling systems found in animals that are mediated by cell-surface receptors with signal-transducing protein kinase activity. PMID- 17841713 TI - Atomic Control of the SrTiO3 Crystal Surface. AB - The atomically smooth SrTiO(3) (100) with steps one unit cell in height was obtained by treating the crystal surface with a pH-controlled NH(4)F-HF solution. The homoepitaxy of SrTiO(3) film on the crystal surface proceeds in a perfect layer-by-layer mode as verified by reflection high-energy electron diffraction and atomic force microscopy. Ion scattering spectroscopy revealed that the TiO(2) atomic plane terminated the as-treated clean surface and that the terminating atomic layer could be tuned to the SrO atomic plane by homooepitaxial growth. This technology provides a well-defined substrate surface for atomically regulated epitaxial growth of such perovskite oxide films as YBa(2)Cu(3)O(7 delta). PMID- 17841714 TI - Meltwater input to the southern ocean during the last glacial maximum. AB - Three records of oxygen isotopes in biogenic silica from deep-sea sediment cores from the Atlantic and Indian sectors of the Southern Ocean reveal the presence of isotopically depleted diatomaceous opal in sediment from the last glacial maximum. This depletion is attributed to the presence of lids of meltwater that mixed with surface water along certain trajectories in the Southern Ocean. An increase in the drainage from Antarctica or extensive northward transport of icebergs are among the main mechanisms that could have produced the increase in meltwater input to the glacial Southern Ocean. Similar isotopic trends were observed in older climatic cycles at the same cores. PMID- 17841715 TI - Exsolution in ferromagnesian olivine of the divnoe meteorite. AB - Ferromagnesian olivine, one of the most common minerals in the solar system, has been widely regarded as a continuous solid solution, although several thermodynamic analyses have suggested the possibility of a miscibility gap at low temperatures. Natural ferromagnesian olivine from the Divnoe meteorite contains compositionally different exsolution lamellae, providing direct evidence for the existence of a miscibility gap in iron-magnesium olivine solid solutions. PMID- 17841716 TI - Teleseismic search for slow precursors to large earthquakes. AB - Some large earthquakes display low-frequency seismic anomalies that are best explained by episodes of slow, smooth deformation immediately before their high frequency origin times. Analysis of the low-frequency spectra of 107 shallow focus earthquakes revealed 20 events that had slow precursors (95 percent confidence level); 19 were slow earthquakes associated with the ocean ridge transform system, and 1 was a slow earthquake on an intracontinental transform fault in the East African Rift system. These anomalous earthquakes appear to be compound events, each comprising one or more ordinary (fast) ruptures in the shallow seismogenic zone initiated by a precursory slow event in the adjacent or subjacent lithosphere. PMID- 17841717 TI - Nanoscale imaging of molecular adsorption. AB - In situ atomic force microscope observations were made of the adsorption of anions (1- or 2-) of the organic diacid 5-benzoyl-4-hydroxy-2 methoxybenzenesulfonic acid from aqueous solution onto the (0001) surface of hydrotalcite (HT), a layered clay. This adsorption process is believed to mimic the ion-exchange reactions that occur within the layers of HT and other layered clays. Atomic force microscope images of the (0001) surfaces of HT, acquired in aqueous solutions, reveal an ordered structure with respect to magnesium and aluminum atoms. In the presence of the anions, atomic force microscopy indicates pH-dependent adsorption onto the formally cationic HT surface. The anion coverage is governed by electroneutrality and steric interactions between the bulky anions within the adsorbed layer, whereas the orientation of the anions with respect to the HT surface is dictated by coulombic interactions and hydrogen bonding between the anion's sulfonate moiety and clay hydroxyl triads. These observations reveal that the reversible adsorption of molecular species can be examined directly by in situ atomic force microscopy, providing details of surface stoichiometry and adlayer symmetry on the local, molecular level. PMID- 17841718 TI - Wolves, moose, and tree rings on isle royale. AB - Investigation of tree growth in Isle Royale National Park in Michigan revealed the influence of herbivores and carnivores on plants in an intimately linked food chain. Plant growth rates were regulated by cycles in animal density and responded to annual changes in primary productivity only when released from herbivory by wolf predation. Isle Royale's dendrochronology complements a rich literature on food chain control in aquatic systems, which often supports a trophic cascade model. This study provides evidence of top-down control in a forested ecosystem. PMID- 17841719 TI - Strontium isotopes in mid-cretaceous seawater. PMID- 17841720 TI - Response. PMID- 17841722 TI - Vignettes: committee work. PMID- 17841721 TI - Evolutionist. PMID- 17841723 TI - The golden bough. PMID- 17841724 TI - Metal ions at work. PMID- 17841725 TI - Products & materials. PMID- 17841726 TI - THE PROBLEM OF DEVELOPMENT. PMID- 17841727 TI - THE AMERICAN PALEONTOLOGICAL SOCIETY. SECTION A--VERTEBRATA. PMID- 17841728 TI - THE ASSOCIATION OF AMERICAN GEOGRAPHERS. PMID- 17841730 TI - DOPPLER'S PRINCIPLE AND LIGHT-BEATS. PMID- 17841729 TI - CONSULTING EXPERTS IN LIBRARIES. PMID- 17841731 TI - THE STORAGE OF MICROSCOPIC SLIDES. PMID- 17841732 TI - RECENT ZOOPALEONTOLOGY. PMID- 17841733 TI - NOTE ON THE BROAD WHITE FISH. PMID- 17841734 TI - INAUGURAL ADDRESS. PMID- 17841736 TI - CONCERNING RECENT AURORAS, MAY 13 AND MAY 14, 1921. PMID- 17841735 TI - SCIENCE AND COMMUNITY TRUSTS. PMID- 17841737 TI - THE LANDSLIDE NEAR MONT BLANC. PMID- 17841738 TI - EXTRA-MUNDANE LIFE: A COMMENT. PMID- 17841739 TI - SOIL ACIDITY THE RESULTANT OF CHEMICAL PHENOMENA. PMID- 17841740 TI - THE AMERICAN MATHEMATICAL SOCIETY. PMID- 17841741 TI - COMMENT AND CRITICISM. PMID- 17841742 TI - ECONOMIC LAWS AND METHODS. PMID- 17841743 TI - CONVOCATION OF THE UNIVERSITY OF THE STATE OF NEW YORK. PMID- 17841744 TI - THE INDIAN SURVEY REPORT. PMID- 17841745 TI - LONDON LETTER. PMID- 17841746 TI - A SALT-MINE IN WESTERN NEW YORK. PMID- 17841747 TI - A most extraordinary structure. PMID- 17841748 TI - Bird-killing sparrows. PMID- 17841750 TI - A bright meteor. PMID- 17841749 TI - Inoculation for the prevention of yellew-fever. PMID- 17841751 TI - Barometer exposure. PMID- 17841753 TI - MODERN EXPLOSIVES AND FLUID FUELS. PMID- 17841752 TI - THE TIME-RELATIONS OF MENTAL PHENOMENA. PMID- 17841755 TI - HEALTH MATTERS. PMID- 17841754 TI - Decrease of Tuberculosis in England. PMID- 17841756 TI - LOW WATER IN BOILERS. PMID- 17841757 TI - The "Barking Sands" of the Hawaiian Islands. PMID- 17841758 TI - Dr. A. Graham Bell's Studies on the Deat. PMID- 17841759 TI - Fishery conservation. PMID- 17841761 TI - Letters to the editor. PMID- 17841760 TI - Fetal research. PMID- 17841763 TI - The problem of urban dogs. PMID- 17841762 TI - Optical brighteners and social responsibility. PMID- 17841764 TI - Chiropractic: Healing or Hokum? HEW Is Looking for Answers. PMID- 17841766 TI - Science and its critics: must rationality be rationed? PMID- 17841765 TI - Putting it together for science at the state department. PMID- 17841767 TI - Oceans bills on course. PMID- 17841768 TI - Cancer claim retracted. PMID- 17841769 TI - Cancer cure promised. PMID- 17841770 TI - Trident: Lawsuit Challenges the Navy's Billion-Dollar Baby. PMID- 17841771 TI - Nerve growth factor: regulatory role examined. PMID- 17841772 TI - !Kung hunter-gatherers: feminism, diet, and birth control. PMID- 17841773 TI - Salt fingers observed in the mediterranean outflow. AB - Salt fingers, convection cells which constitute a possible mixing mechanism of the ocean, have now been observed in the Mediterranean outflow. The fingers, 6 millimeters in diamneter and 24 centimeters long, were photographed below the salinity maximum of the outflow, in an interface 22 centimeters thick where temperature and salinity decreased O. 15 degrees C and 0.03 per mil, respectively. PMID- 17841774 TI - Attempt to date early South african hominids by using fission tracks in calcite. AB - Calcite crystals extracted from marrow cavities of bones found in hominid-bearing breccias from Makapansgat and Swartkrans were studied for fossil tracks. The absence of the expected numbers of tracks in these and in calcites from Beds I and II, Olduvai Gorge, combined with the results of laboratory heating experiments, indicates that track annealing has occurred at ambient temperatures and precludes the widespread use of calcite for fission track dating. PMID- 17841775 TI - Toxicity in sponges and holothurians: a geographic pattern. AB - Toxicity in sponges and holothurians is inversely related to latitude and may reach 100 percent for holothurians in high-diversity coral reefs. Evidence from approximately 700 experiments and from underwater observations suggests that predation by fish has resulted in natural selection for noxious and toxic chemical compounds in species within these taxa. PMID- 17841776 TI - Strategies for study of synaptic organization. PMID- 17841777 TI - Receint deaths. PMID- 17841778 TI - PRODUCTS and MATERIALS. PMID- 17841779 TI - Publications Received. PMID- 17841781 TI - Reporting Science. PMID- 17841780 TI - The Criticism of Scientific Books. PMID- 17841782 TI - The Impact of Science on Literature. PMID- 17841783 TI - A Blast for "Formicology". PMID- 17841784 TI - Circling Planets. PMID- 17841785 TI - "Official Views" from the GPO. PMID- 17841786 TI - National Conference of Science for Peace. PMID- 17841787 TI - PHYSICAL CHEMISTRY IN THE SERVICE OF PHYTOGEOGRAPHY. PMID- 17841788 TI - A REMARKABLE COINCIDENCE. PMID- 17841789 TI - REPORT OF DR. E. H. WILLIAMS ON THE FIRST PHASE OF PENNSYLVANIA GLACIATION. PMID- 17841790 TI - A RHYTHMICAL "HEAT PERIOD" IN THE GUINEA-PIG. PMID- 17841791 TI - THE IOWA ACADEMY OF SCIENCE. PMID- 17841793 TI - PRESIDENTIAL ADDRESS BEFORE THE SOCIETY FOR THE PROMOTION OF ENGINEERING EDUCATION.dagger. PMID- 17841792 TI - DANIEL G. BRINTON. PMID- 17841794 TI - WORK OF TIE U. S. GEOLOGICAL SURVEY. PMID- 17841795 TI - THE FOEHN WINDS OF SWITZERLAND. PMID- 17841796 TI - ASTIRONOMICAL NOTES. PMID- 17841797 TI - THE OPENING OF THE MOUTH AS EXPRESSION. PMID- 17841798 TI - NOTES ON PHYSICS. PMID- 17841799 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17841800 TI - Global cooling? AB - The world's inhabitants, including Scientists, live primarily in the Northern Hemisphere. It is quite natural to be concerned about events that occur close to home and neglect faraway events. Hence, it is not surprising that so little attention has been given to the Southern Hemisphere. Evidence for global cooling has been based, in large part, on a severe cooling trend at high northern latitudes. This article points out that the Northern Hemisphere cooling trend appears to be out of phase with a warming trend at high latitudes in the Southern Hemisphere. The data are scanty. We cannot be sure that these temperature fluctuations are be not the result of natural causes. How it seems most likely that human activity has already significantly perturbed the atmospheric weather system. The effect of particulate matter pollution should be most severe in the highly populated and industrialized Northern Hemisphere. Because of the rapid diffusion of CO(2) molecules within the atmosphere, both hemispheres will be subject to warming due to the atmospheric (greenhouse) effect as the CO(2) content of the atmosphere builds up from the combustion of fossil fuels. Because of the differential effects of the two major sources of atmospheric pollution, the CO(2) greenhouse effect warming trend should first become evident in the Southern Hemisphere. The socioeconomic and political consequences of climate change are profound. We need an early warning system such as would be provided by a more intensive international world weather watch, particularly at high northern and southern latitudes. PMID- 17841801 TI - Calibrating duckweeds: light, clocks, metabolism, flowering. AB - The roles of photoperiodism and related light-dependent and hormonal processes in plants are not well understood. Rapid growth, aquatic habit, and adaptability to axenic culture make the Lemnaceae, or duckweeds, excellent material for investigating these topics and others in which highly defined conditions or the presence of organic substances are crucial. As a major example among several that are described, recent work with one species suggests a relation between some features of carbon dioxide flux and the photoperiodic timing mechanism, thus providing a system in which the biochemical basis of the latter may be explored. PMID- 17841802 TI - Symbiosis between the Earth and humankind. PMID- 17841803 TI - Carter as scientist or engineer: what are his credentials? PMID- 17841804 TI - New CIA--Research, Anyone? PMID- 17841805 TI - If I were the science adviser: some luminaries have their say. PMID- 17841806 TI - Stever gets delayed nod. PMID- 17841807 TI - New data suggest decline in industry R & d. PMID- 17841808 TI - Confidentiality: court declares researcher can protect sources. PMID- 17841809 TI - Recombinant DNA at white house. PMID- 17841810 TI - Computational chemistry: getting more from a minicomputer. PMID- 17841811 TI - Chemists' first try at big science. PMID- 17841812 TI - Interciencia welcomed at d.C. Reception. PMID- 17841813 TI - Scientists and Lawyers Explore Weather Modification at AAAS-ABA Conference. PMID- 17841814 TI - Puerto ricans investigate underrepresentation in science professions. PMID- 17841815 TI - Habitat: a festive air, serious business. PMID- 17841816 TI - On ptolemy as the greatest astronomer of antiquity. PMID- 17841817 TI - Changes in biology. PMID- 17841818 TI - Perceptual development. PMID- 17841819 TI - Light scattering by irregular randomly oriented particles. AB - A method for calculating light scattering by irregular randomly oriented particles yields results that are in good agreement with experimental data. The method is based on the assumption that surface waves are present in scattering by spherical particles, but they are absent in scattering by irregular particles. PMID- 17841820 TI - Hooked trichomes: a physical plant barrier to a major agricultural pest. AB - Hooked epidermal appendages (trichomes) on leaves of field bean cultivars effectively capture nymph and adult leafhoppers. Frequency of capture and capture mortality are highly correlated with trichome density. Hooked trichomes inserted at angles less than 30 degrees are ineffective in capture. PMID- 17841821 TI - Fog catchment sand trenches constructed by tenebrionid beetles, lepidochora, from the namib desert. AB - Three species of coastal Namib Desert tenebrionid beetles (Lepidochora) build trenches on desert sand dunes. Trenches are constructed perpendicular to fog winds and concentrate moisture during fogs. The beetles return along the ridges of the trenches extracting water from them. The water content of a population of these beetles increased by 13.9 percent during one fog. PMID- 17841822 TI - Combustion metamorphism in southern california. AB - In several places in Southern California bituminous sediments of the Monterey Formation-siliceous shales, phosphatic rocks, dolomites, and arkoses-were affected during the Pleistocene and as late as the l9th century by spontaneous subsurface combustion of organic matter, during which temperatures up to 1600 degrees C were reached. This oxidative heating (combustion metamorphism) affected rock complexes over areas of tens of square kilometers that tend to occur in clusters. As a result of these processes, the rocks recrystallized and partially melted to form pseudomagmas which intruded the country rocks. The chemical compositions of these melts differ from those of igneous magmas. Acid and intermediate siliceous melts as well as phosphatic melts have formed. These two types are generally immiscible. The following high-temperature minerals were determined: alpha- and beta-cristobalite, quartz, calcic plagioclase, diopsidic pyroxene, wollastonite, cordierite, graphite, fluorapatite, and fluorite; at lower temperature pyrite, gypsum, aragonite, calcite, jarosite, and hexahydrite crystallized. PMID- 17841823 TI - Magnetic direction finding: evidence for its use in migratory indigo buntings. AB - The orientational capabilities of caged migratory indigo buntings were studied under differing magnetic field conditions. When tested in a situation allowing minimal exposure to visual cues but in the presence of the normal geomagnetic field, the birds demonstrated a significant orientation in the appropriate migratory direction (to the north). When the horizontal component of the magnetic field was deflected clockwise 120 degrees by activation of Helmholtz coils surrounding the cage, the orientation of the buntings shifted accordingly (clockwise to geographic east-southeast). These results suggest that indigo buntings are not only able to detect the geomagnetic field, but also can use this information in the finalization of their migratory direction. PMID- 17841824 TI - Biogeography of free-living soil nematodes from the perspective of plate tectonics. AB - In this first biogeographical synthesis based on the morphology and known distribution of a group of free-living soil nematodes, data indicate a pre Jurassic origin followed by West Gondwanaland radiation for some genera and Laurasian radiation for others. PMID- 17841825 TI - New publications. PMID- 17841826 TI - THE USE OF THE FRENCH ACADEMY. PMID- 17841827 TI - AMERICAN FLASH LANGUAGE AGAIN. PMID- 17841828 TI - Aquatic respiration of soft-shelled turtles. PMID- 17841829 TI - Lower Silurian fossils at Canaan, N.Y. PMID- 17841830 TI - Composite portraiture. PMID- 17841831 TI - The magnetic declination in 1728. PMID- 17841832 TI - Electric measuring apparatus. PMID- 17841833 TI - AN AVERAGE DAY IN CAMP AMONG THE SIOUX. PMID- 17841834 TI - THE CAROLINE ISLANDS. PMID- 17841835 TI - SCIENCE IN COMMON SCHOOLS. PMID- 17841837 TI - TOUGHENED GLASS. PMID- 17841836 TI - THE RESULTS OF THE KRAKATOA ERUPTION. PMID- 17841838 TI - PHOSPHORESCENCE OF MARINE ANIMALS. PMID- 17841839 TI - THE RELATIONSHIPS BETWEEN DINOSAURS AND BIRDS. PMID- 17841840 TI - THE LEAVES OF THE PITCHER-PLANT. PMID- 17841842 TI - SOME WORKS ON GEOLOGY AND GEOGRAPHY. PMID- 17841841 TI - INSULAR FLORAS. PMID- 17841843 TI - INFECTIOUS DISEASES. PMID- 17841844 TI - This week in science. PMID- 17841845 TI - Exploratory basic research. PMID- 17841846 TI - Transportation costs and the national debt. PMID- 17841848 TI - Recovering funds. PMID- 17841847 TI - Corrections and clarifications. AB - The Random Sample item, "Russians, U.S. differ on Arctic sub threat" (25 June, p. 1881) should have said that the Sellafield nuclear reprocessing plant has dumped 1 million curies of cesium-137 (not plutonium) into the North Sea. The plant has dumped more than 18,000 curies of plutonium. PMID- 17841849 TI - Megaproject support. PMID- 17841850 TI - Sciencescope. PMID- 17841851 TI - Weapons labs in a new world. PMID- 17841852 TI - Are two labs too many? PMID- 17841853 TI - Senate Vote Lifts Prospects for SSC. PMID- 17841854 TI - Reinventing the automobile--and government r&d. PMID- 17841855 TI - E-mail withdrawal prompts spasm. PMID- 17841856 TI - Congress Boosts NSF, NASA Budgets. PMID- 17841857 TI - Moving science from museum to school. PMID- 17841859 TI - Scanning probe microscopes look into new territories. PMID- 17841858 TI - A new form of strange matter and new hope for finding it. PMID- 17841860 TI - New look at neolithic sites reveals complex societies. PMID- 17841861 TI - NSF Joins the Crowd In New Program. PMID- 17841862 TI - Draper Prize to Father of FORTRAN. PMID- 17841863 TI - Pumping up science awareness in europe. PMID- 17841864 TI - Quantum constructions. PMID- 17841865 TI - Radio emission from the heliopause triggered by an interplanetary shock. AB - A strong heliospheric radio emission event has been detected by Voyagers 1 and 2 in the frequency range of 2 to 3 kilohertz. This event started in July 1992 and is believed to have been generated at or near the heliopause by an interplanetary shock that originated during a period of intense solar activity in late May and early June 1991. This shock produced large plasma disturbances and decreases in cosmic ray intensity at Earth, Pioneers 10 and 11, and Voyagers 1 and 2. The average propagation speed estimated from these effects is 600 to 800 kilometers per second. After correction for the expected decrease in the shock speed in the outer heliosphere, the distance to the heliopause is estimated to be between 116 and 177 astronomical units. PMID- 17841866 TI - A Spatially Resolved X-ray Image of a Star Like the Sun. AB - Observations made with the x-ray satellite ROSAT (Roentgen Satellite) have produced the first spatially resolved x-ray image of a corona around a star like our sun. The star is the secondary in the eclipsing binary system alpha Coronae Borealis (CrB), which consists of one star of spectral type A0V and one of type G5V. The x-ray light curve of alpha CrB shows a total x-ray eclipse during secondary optical minimum, with the G star behind the A star. The totality of the eclipse demonstrates that the A-type component in alpha CrB is x-ray dark and that the x-ray flux arises exclusively from the later-type companion. The x-ray eclipse ingress and egress are highly asymmetric compared with the optical eclipse, indicating a highly asymmetric x-ray intensity distribution on the surface of the G star. From a detailed modeling of the ingress and egress of the x-ray light curve, an eclipse map of the G star was constructed by a method based on an optimization by simulated annealing. PMID- 17841867 TI - Confinement of electrons to quantum corrals on a metal surface. AB - A method for confining electrons to artificial structures at the nanometer lengthscale is presented. Surface state electrons on a copper(111) surface were confined to closed structures (corrals) defined by barriers built from iron adatoms. The barriers were assembled by individually positioning iron adatoms with the tip of a 4-kelvin scanning tunneling microscope (STM). A circular corral of radius 71.3 A was constructed in this way out of 48 iron adatoms. Tunneling spectroscopy performed inside of the corral revealed a series of discrete resonances, providing evidence for size quantization. STM images show that the corral's interior local density of states is dominated by the eigenstate density expected for an electron trapped in a round two-dimensional box. PMID- 17841868 TI - Enhanced c2 yields from methane oxidative coupling by means of a separative chemical reactor. AB - Of the processes for converting natural gas into a more useful chemical feedstock, the oxidative coupling of methane to form ethane and ethylene (C(2)) has perhaps been the most intensively investigated in recent years, but it has proved extremely difficult to obtain C(2) yields in excess of 20 to 25%. Methane oxidative coupling was carried out in a separative chemical reactor that simulated a countercurrent chromatographic moving-bed. This reaction gives 65% methane conversion, 80% C(2) selectivity, and a C(2) yield slightly better than 50% with Sm(2)O(3) catalyst at approximately 1000 K. PMID- 17841869 TI - Dissipation of marine stratiform clouds and collapse of the marine boundary layer due to the depletion of cloud condensation nuclei by clouds. AB - When the production of cloud condensation nuclei in the stratocumulus-topped marine boundary layer is low enough, droplet collisions can reduce concentrations of cloud droplet numbers to extremely low values. At low droplet concentrations a cloud layer can become so optically thin that cloud-top radiative cooling cannot drive vertical mixing. Under these conditions, model simulations indicate that the stratocumulus-topped marine boundary layer collapses to a shallow fog layer. Through this mechanism, marine stratiform clouds may limit their own lifetimes. PMID- 17841870 TI - High-Temperature XAS Study of Fe2SiO4 Liquid: Reduced Coordination of Ferrous Iron. AB - X-ray absorption spectroscopy (XAS) of Fe(2+) in Fe(2)SiO(4) liquid at 1575 kelvin and 10(-4) gigapascal (1 bar) shows that the Fe(2+) -O bond length is 1.98 +/- 0.02 angstroms compared with approximately 2.22 angstroms in crystalline Fe(2)SiO(4) (fayalite) at the melting point (1478 kelvin), which indicates a decrease in average Fe(2+) coordination number from six in fayalite to four in the liquid. Anharmonicity in the liquid was accounted for using a data analysis procedure. This reduction in coordination number is similar to that observed on the melting of certain ionic salts. These results are used to develop a model of the medium-range structural environment of Fe(2+) in olivine-composition melts, which helps explain some of the properties of Fe(2)SiO(4) liquid, including density, viscosity, and the partitioning of iron and nickel between silicate melts and crystalline olivines. Some of the implications of this model for silicate melts in the Earth's crust and mantle are discussed. PMID- 17841872 TI - Ventures in patronage. PMID- 17841871 TI - Teosinte glume architecture 1: A Genetic Locus Controlling a Key Step in Maize Evolution. AB - Teosinte, the probable progenitor of maize, has kernels that are encased in hardened fruitcases, which interfere with the use of the kernels as food. Although the components of the fruitcase are present in maize, their development is disrupted so that the kernels are not encased as in teosinte but exposed on the ear. The change from encased to exposed kernels represents a key step in maize evolution. The locus that largely controls this morphological difference between maize and teosinte, teosinte glume architecture 1, is described and genetically mapped. PMID- 17841873 TI - Learning to speak. PMID- 17841874 TI - Planetary systems. PMID- 17841875 TI - California flora. PMID- 17841876 TI - Vignettes: blank verse. PMID- 17841878 TI - Products & materials. PMID- 17841877 TI - Gordon research conferences. PMID- 17841879 TI - INJURIES FROM CATHODE RAYS. PMID- 17841880 TI - CONCERNING COMETS. PMID- 17841881 TI - THE BEGINNING OF WINTER. PMID- 17841882 TI - CALCIUM AND ALUMINIUM COMPOUNDS FOR CHICKEN SARCOMA. PMID- 17841883 TI - THE BRAINS OF NIKOLAI LENIN AND ANATOLE FRANCE. PMID- 17841884 TI - EXPLORATIONS IN THE BAHAMAS. PMID- 17841885 TI - CHOLERA IN INDIA. PMID- 17841886 TI - SOME APPLICATIONS OF PHYSICAL CHEMISTRY TO MEDICINE. PMID- 17841887 TI - THE ABUSE OF WATER. PMID- 17841888 TI - FRANK W. VERY. PMID- 17841889 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17841890 TI - THE CONTROL OF DIABETES IN SIAM BY THE USE OF SOLANACEOUS PLANTS. PMID- 17841891 TI - E.M.F. INDUCED IN A STRAIGHT WIRE BY A CURRENT IN A PARALLEL STRAIGHT CONDUCTOR. PMID- 17841892 TI - SIR JAGADIS CHUNDER BOSE AND HIS LATEST BOOK. PMID- 17841894 TI - IONIZATION BY POSITIVE IONS. PMID- 17841893 TI - WHEN IS MID-WINTER? PMID- 17841895 TI - CORRELATION BETWEEN ELECTROMOTIVE SERIES AND OXIDATION POTENTIALS AND PLANT AND ANIMAL NUTRITION. PMID- 17841896 TI - INHIBITION OF ENZYMATIC ACTION AS A POSSIBLE FACTOR IN THE RESISTANCE OF PLANTS TO DISEASE. PMID- 17841897 TI - DOCTORATES CONFERRED BY AMERICAN UNIVERSITIES. PMID- 17841898 TI - INERTIA AND GRAVITATION. PMID- 17841899 TI - THE WORK OF THE SOCIETY FOR AGRICULTURAL EDUCATION. PMID- 17841900 TI - THE BRITISH ASSOCIATION. PMID- 17841901 TI - VARIATION AMONG HYDROMEDUSAe. PMID- 17841902 TI - LATERAL LINE ORGANS IN EUNICE AURICULATA n. sp. PMID- 17841903 TI - INTERNATIONAL COMMISSION ON ATOMIC WEIGHTS. PMID- 17841904 TI - EMINENT AMERICAN MEN OF SCIENCE. PMID- 17841905 TI - PLANT EMBRYO-SACS. PMID- 17841906 TI - THE BOYNTON BICYCLE RAILROAD. PMID- 17841907 TI - THE ROLE OF PTOMAINES IN INFECTIOUS DISEASES. PMID- 17841908 TI - RUSSIAN LITERATURE. PMID- 17841910 TI - LEAD-COVERED CABLES. PMID- 17841909 TI - LIGHTNING ON WAR-VESSELS. PMID- 17841911 TI - HEALTH MATTERS. PMID- 17841912 TI - ELECTRICAL NEWS. PMID- 17841913 TI - TOBACCO AND INSANITY. PMID- 17841914 TI - CHOLERA IN ASIATIC TURKEY. PMID- 17841915 TI - THE DREAD OF DEATH. PMID- 17841916 TI - THE FOODS OF DIFFERENT PEOPLES. PMID- 17841917 TI - THE SANDWICH ISLAND LEPER COLONY. PMID- 17841918 TI - TRANSPLANTING OF A CHICKEN'S CORNEA. PMID- 17841919 TI - MALARIAL FEVER IN EASTERN MASSACHUSETTS. PMID- 17841920 TI - PEA-SOUP AS A SUBSTITUTE FOR BEEF-TEA. PMID- 17841921 TI - THE ETIOLOGY OF GOITRE. PMID- 17841922 TI - REPORT OF THE COMMITTEE OF THE NEW YORK STATE MEDICAL SOCIETY ON THE CAUSES AND PREVENTION OF BLINDNESS. PMID- 17841923 TI - INDUSTRIAL NOTES. PMID- 17841924 TI - Map of Niagara Falls. PMID- 17841925 TI - The Telephone for the Prediction of Thunder-Storms. PMID- 17841926 TI - Research management and government accounting. PMID- 17841928 TI - State and local science policy. PMID- 17841927 TI - State and local science policy. PMID- 17841929 TI - Congressional fellowship stipend raised for 1978. PMID- 17841930 TI - Research opportunities in fossil fuels. PMID- 17841931 TI - New copyright law: effects on science, contributors, and users. PMID- 17841932 TI - Structure and properties of metallic glasses. AB - Recent experience has shown that certain metal alloys can be put into glass form by rapid melt-quenching or by various condensation processes. Models for the nature and structure of these glasses are surveyed and shown to be quite parallel to those already developed for the more common nonmetallic glasses. The rather unique magnetic, superconducting, and mechanical properties and the technical potential of metallic glasses are also discussed. PMID- 17841933 TI - Harvard gene splicer told to halt. PMID- 17841934 TI - Photocopying: new copyright law changes the ground rules. PMID- 17841935 TI - Peat for fuel: development pushed by big corporate farm in Carolina. PMID- 17841936 TI - Radicals and the universities: "critical mass" at u. Mass. PMID- 17841937 TI - New crop of astronauts. PMID- 17841938 TI - Kentucky unhappy with atom dump. PMID- 17841940 TI - Position-Sensitive Detectors: An "Electronic Film" for X-rays. PMID- 17841939 TI - Assertion of dolphin rights fails in court. PMID- 17841941 TI - Information theory: a surprising proof. PMID- 17841942 TI - AAAS Socio-Psychological Prize. PMID- 17841943 TI - AAAS Sections, Affiliates, Committees Plan Annual Meeting Events. PMID- 17841945 TI - Amendment to AAAS Constitution. PMID- 17841944 TI - Deans review short courses. PMID- 17841946 TI - I See What You're Saying .. PMID- 17841947 TI - SB&F Needs Reviewers. PMID- 17841948 TI - Meeting information. PMID- 17841950 TI - Science and technology: new tools, new dimensions. PMID- 17841949 TI - Science and technology: new tools, new dimensions. PMID- 17841951 TI - Paleontologists confronting macroevolution. PMID- 17841953 TI - Plate tectonics. PMID- 17841952 TI - Cancer research. PMID- 17841954 TI - Viking first encounter of phobos: preliminary results. AB - During the last 2 weeks of February 1977, an intensive scientific investigation of the martian satellite Phobos was conducted by the Viking Orbiter-1 (VO-1) spacecraft. More than 125 television pictures were obtained during this period and infrared observations were made. About 80 percent of the illuminated hemisphere was imaged at a resolution of about 30 meters. Higher resolution images of limited areas were also obtained. Flyby distances within 80 kilometers of the surface were achieved. An estimate of the mass of Phobos (GM) was obtained by observing the effect of Phobos's gravity on the orbit of VO-1 as sensed by Earth-based radiometric tracking. Preliminary results indicate a value of GM of 0.00066 +/- 0.00012 cubic kilometer per second squared (standard deviation of 3) and a mean density of about 1.9 +/- 0.6 gram per cubic centimeter (standard deviation of 3). This low density, together with the low albedo and the recently determined spectral reflectance, suggest that Phobos is compositionally similar to type I carbonaceous chondrites. Thus, either this object formed in the outer part of the asteroid belt or Lewis's theory that such material cannot condense at 1.5 astronomical units is incorrect. The data on Phobos obtained during this first encounter period are comparable in quantity to all of the data on Mars returned by Mariner flights 4, 6, and 7. PMID- 17841955 TI - The composition of phobos: evidence for carbonaceous chondrite surface from spectral analysis. AB - A reflectance spectrum of Phobos (from 200 to 1100 nanometers) has been compiled from the Mariner 9 ultraviolet spectrometer, Viking lander imaging, and ground based photometric data. The reflectance of the martian satellite is approximately constant at 5 percent from 1100 to 400 nanometers but drops sharply below 400 nanometers, reaching a value of 1 percent at 200 nanometers. The spectral albedo of Phobos bears a striking resemblance to that of asteroids (1) Ceres and (2) Pallas. Comparison of the reflectance spectra of asteroids with those of meteorites has shown that the spectral signature of Ceres is indicative of a carbonaceous chondritic composition. A physical explanation of how the compositional information is imposed on the reflectance spectrum is given. On the basis of a good match between the reflectance spectra of Phobos and Ceres and the extensive research that has been done to infer the composition of Ceres, it seems reasonable to believe that the surface composition of Phobos is similar to that of carbonaceous chondrites. This suggestion is consistent with the recently determined low density of Mars's inner satellite. Our result and recent Viking noble gas measurements suggest different modes of origin for Mars and Phobos. PMID- 17841956 TI - Multicolor observations of phobos with the viking lander cameras: evidence for a carbonaceous chondritic composition. AB - The reflectivity of Phobos has been determined in the spectral region from 0.4 to 1.1 micrometers from images taken with a Viking lander camera. The reflectivity curve is flat in this spectral interval and the geometric albedo equals 0.05 +/- 0.01. These results, together with Phobos's reflectivity spectrum in the ultraviolet, are compared with laboratory spectra of carbonaceous chondrites and basalts. The spectra of carbonaceous chondrites are consistent with the observations, whereas the basalt spectra are not. These findings raise the possibility that Phobos may be a captured object rather than a natural satellite of Mars. PMID- 17841957 TI - The Reuss Report. PMID- 17841958 TI - Colony of Hemophilic Dogs. PMID- 17841959 TI - Letters to the Editor. PMID- 17841960 TI - Letters to the Editor. PMID- 17841961 TI - Letters to the Editor. PMID- 17841962 TI - The Camelot Affair. PMID- 17841963 TI - Exclusive Rights. PMID- 17841964 TI - The Inner Calm. PMID- 17841965 TI - Ages of Experimental Animals. PMID- 17841966 TI - Monod and His Cello. PMID- 17841967 TI - Psychological Testing and the Invasion of Privacy. PMID- 17841968 TI - Antarctica--Continent of International Science. PMID- 17841969 TI - Fishing Treaties and Salmon of the North Pacific. PMID- 17841970 TI - Money for Science: Budget Faces Pressure from Vietnam Conflict. PMID- 17841971 TI - Education: New Commissioner Champions Change and Reform. PMID- 17841972 TI - Lead Isotopes and the Age of the Earth. AB - Calculations based on comparison of the isotopic composition of lead from iron meteorites with that of various modern terrestrial leads have placed the age of the earth at around 4550 million years. However, recent data from young volcanic rocks reveal that modern terrestrial lead can have a wide range in isotopic composition. The variations in its coinposition mean that one or more of the assumptions used in the age calculation have been violated. We modified the usual approach by comparing meteorite lead with lead from rocks 2700 million years old, from the Canadian Shield. Using this method and the same constants and assumptions utilized in the earlier calculations we calculated an age of 4750 +/- 50 million years for the earth. The earth may be approximately 200 million years older than previously thought; alternatively, primordial terrestrial lead may not have had the same isotopic composition as lead in iron meteorites does. PMID- 17841973 TI - Geology of the Central Portion of the Queen Maud Range, Transantarctic Mountains. AB - The geologic section consists of a folded and metamorphosed basement complex of geosynclinal and nearshore sediments and intrusives, a thick sequence of nearshore and terrestrial sediments of middle to late Paleozoic age, and thick diabase sheets and basalt flows of Jurassic age. Block faulting, probably through during the Miocene age, produced the which has been carved into its present from by glaciers. PMID- 17841974 TI - Migrant Sound Scatterers: Interaction with the Sea Floor. AB - Studies on the coast of Baja California show that oceanic zooplankters carried into shallow water provide abundant food for resident predators. The vertically migrating zooplankters apparently are vulnerable when they encounter the sea floor in shoal areas. This ecologically significant mechanism may be of importance to fisheries and military operations. PMID- 17841975 TI - Strontium-Rubidium Age of an Iron Meteorite. AB - The isotopic compositions and concentrations of rubidium and strontium were determined in silicate nodules contained in Weekeroo Station meteorite, a brecciated coarse octahedrite. The strontium had a Sr(87):Sr(86) range from 0.729 to 0.768, showing considerable enrichment in Sr(87) in coinparison with achondrites. Data for six samples of nodules lie on a straight line on the Sr-Rb evolution diagram, with an initial Sr(87):Sr(86) ratio of 0.696 to 0.702; the slope is 0.0674, corresponding to an age of 4.7 x 10(9) years for lambda = 1.39 x 10(-11) year(-1). These data agree with the previously assigned ages for the formation of stony meteorites and the earth; they support the conclusion that the major period of chemical and physical differentiation in the solar system occurred in a narrow interval at about this time. This result disagrees with the Ar(40)-K(40) ages of 5 to 13 x 10(9) years determined from other iron meteorites. A wide variety of isotopic-age investigations now seem experimentally feasible on iron meteorites that contain silicates. PMID- 17841976 TI - Germination of Lily Pollen: Respiration and Tube Growth. AB - Germinating pollen of Lilium longiflorum (cv. Ace) briefly exhibited a high rate of respiration before pollen tubes began to grow. A second period of high respiration occurred while tubes were growing. Between these periods respiration proceeded at a lower rate. Respiration was stimulated by 2,4-dinitrophenol to occur at approximately the same rate in all three periods. PMID- 17841977 TI - "Negative" Crystals in Ice: A Method for Growth. AB - Holes bounded by crystal-lographic faces, or "negative" crystals, may be made in ice by inserting a hypodermic needle and connecting it to a vacuum. The evaporation habit changes as a function of temperature and growth rate. This procedure is a simple way of producing mirror-smooth, uncontaminated, crystallographic surfaces in compounds which have high vapor pressure. PMID- 17841978 TI - Ice-Rafted Detritus as a Climatic Indicator in Antarctic Deep-Sea Cores. AB - Ice-rafted detritus is readily identified in sediment cores raised from the deep ocean floor around Antarctica. A few cores have reached a depth below which no ice-rafted material is found. This depth is interpreted as indicating the establishment of earliest Pleistocene glaciation in the Southern Hemisphere. It is just below a depth where there is a change in assemblages of Radiolaria which Hays associates with the Pliocene-Pleistocene boundary. The presence of ice rafted material throughout the upper zone in cores taken south of the Polar Front indicates continuity of glaciation in Antarctica. Further north, near 45 degrees S in the Argentine Basin, zonation of the ice-rafted detritus can be used to delineate glacial stages of the Pleistocene. PMID- 17841979 TI - Differential Enzymatic Activity in Ecological Races of Typha latifolia L. AB - Glycolic acid oxidase activity in chloroplast fragments from ecotypic populations of T. latifolia L. was much greater, particularly at lower temperatures, in populations adapted to a semimaritime climate than in populations adapted to a continental climate. PMID- 17841981 TI - Optical Activity in the Orgueil Meteorite. PMID- 17841980 TI - Flora and Fauna on Backs of Large Papuan Moss-Forest Weevils. AB - Large, living, flightless weevils feeding on leaves of woody plants high moss forest on various New Guinea mountain ranges have plant growth on their backs. Fungi and algae have been found on 11 species of Gymnopholus, lichens on six species, and liverworts on one species. In other genera of weevils, on the same mountains, there are additional specific associations with fungi, algae, lichens, and liverworts. The fungi and lichens, at least, are inhabited by oribatid mites of a new family, which may spread the plants from beetle to beetle. Also, nematodes, rotifers, psocids, and diatoms occur among the plants. Specialized scales or hairs, and a secretion, in depressions on the weevils' backs, appear to be associated with cpcouragement of the plant growth. Mutualistic symbiotic relationships seem to be clearly indicated. PMID- 17841982 TI - Genetic Control of Differentiation. PMID- 17841983 TI - Forthcoming Events. PMID- 17841984 TI - COMMENT AND CRITICISM. PMID- 17841986 TI - GEOGRAPHICAL NOTES. PMID- 17841985 TI - THE COAST SURVEY AND THE NAVY. PMID- 17841987 TI - COMPOSITE PORTRAITS OF AMERICAN INDIANS. PMID- 17841988 TI - PARIS LETTER. PMID- 17841989 TI - Science at Cornell. PMID- 17841990 TI - Phylloxera. PMID- 17841991 TI - Pompous prolixity of the French. PMID- 17841992 TI - A swindler abroad again. PMID- 17841993 TI - Poison rings. PMID- 17841994 TI - Topographical models or relief-maps. PMID- 17841995 TI - CONSERVATION AND SCIENTIFIC FORECAST. PMID- 17841997 TI - THE ENGINEERS COUNCIL FOR PROFESSIONAL DEVELOPMENT. PMID- 17841996 TI - TOWARDS A NEW BIOCHEMISTRY? PMID- 17841998 TI - FELLOWSHIPS OF THE LALOR FOUNDATION. PMID- 17841999 TI - HONORARY DEGREES CONFERRED BY YALE UNIVERSITY. PMID- 17842000 TI - HONORARY DEGREES CONFERRED BY PRINCETON UNIVERSITY. PMID- 17842001 TI - PROMOTIONS AND NEW APPOINTMENTS AT THE ROCKEFELLER INSTITUTE FOR MEDICAL RESEARCH. PMID- 17842002 TI - ELECTIONS TO FELLOWSHIP IN THE ROYAL SOCIETY, LONDON. PMID- 17842003 TI - A GROWTH-DEPRESSANT SUBSTANCE FROM YEAST. PMID- 17842004 TI - RATE OF SURFACE RETREAT OF SEA CLIFFS BASED ON DATED INSCRIPTIONS. PMID- 17842006 TI - FURTHER COMMENT ON PRESERVATION OF NATURAL AREAS. PMID- 17842005 TI - DIETARY REPAIR OF EXPERIMENTAL CARIES. PMID- 17842007 TI - MAN'S BIOLOGICAL DESTINY. PMID- 17842008 TI - THE ILLINOIS STATE ACADEMY OF SCIENCE. PMID- 17842009 TI - THE EFFECT OF 2, 3, 5, TRIIODOBENZOATE ON THE GROWTH OF TUBERCLE BACILLI. PMID- 17842010 TI - THE MINIMUM BASE VALUE OF HEAT PRODUCTION IN ANIMALS. PMID- 17842011 TI - ESTIMATION, ISOLATION AND IDENTIFICATION OF AUXINS IN PLANT MATERIAL. PMID- 17842012 TI - AN IMPROVED GAS BURNER FOR SMOKING KYMOGRAPH PAPER. PMID- 17842013 TI - OXIDATION PREVENTION. PMID- 17842015 TI - THE DUBLIN MEETING OF THE BRITISH ASSOCIATION, SEPTEMBER 2-9, 1908. PMID- 17842014 TI - THE GEOGRAPHICAL DISTRIBUTION OF THE STUDENT BODY AT A NUMBER OF UNIVERSITIES AND COLLEGES. PMID- 17842016 TI - SIXTEENTH INTERNATIONAL CONGRESS OF AMERICAINISTS. PMID- 17842017 TI - THE FOURTH INTERNATIONAL FISHERY CONGRESS. PMID- 17842018 TI - MEMORIAL EXERCISES IN HONOR OF WILLIAM F. VILAS. PMID- 17842019 TI - THE DARWIN ANNIVERSARY MEETING OF THE AMERICAN ASSOCIATION. PMID- 17842020 TI - THE TEACHING OF MATHEMATICS TO ENGINEERS. PMID- 17842021 TI - CONCERNING THE REAL UNICORN. PMID- 17842022 TI - NOTES ON ENTOMOLOGY. PMID- 17842023 TI - ON A COMMUNICATION BETWEEN THE AIR-BLADDER AND THE EAR IN CERTAIN SPINY-RAYED FISHES. PMID- 17842024 TI - A NEW SOIL SAMPLER. PMID- 17842025 TI - NOTE ON THE CRYSTAL FORM OF BENITOITE. PMID- 17842026 TI - DISCOVERY OF CRETACEOUS AND OLDER TERTIARY STRATA IN MONGOLIA. PMID- 17842027 TI - THE FEEDING POWER OF PLANTS. PMID- 17842029 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17842028 TI - THE TEACHING OF EVOLUTION. PMID- 17842030 TI - THE MEALY-BUG CALLED PSEUDOCOCCUS BROMELIAe, AND OTHER COCCIDS. PMID- 17842031 TI - THE ZODIACAL LIGHT. PMID- 17842032 TI - THE DETERMINATION OF FAT IN CREAM. PMID- 17842033 TI - DR. LIPMANN'S LABORATORY OF APPLIED PSYCHOLOGY. PMID- 17842035 TI - PHOTOPERIODISM OF WHEAT; A DETERMINING FACTOR IN ACCLIMATIZATION. PMID- 17842034 TI - SHIPMENT OF AMERICAN SCIENTIFIC LITERATURE TO RUSSIA. PMID- 17842036 TI - IMPROVED METHODS IN NEAR INFRA-RED ABSORPTION STUDY. PMID- 17842037 TI - Erratum. AB - In the article "Reexamination of acoustic evidence in the Kennedy assassination" by the Committee on Ballistic Acoustics, National Research Council (8 Oct., p. 127), the probability given on page 130, column 1, line 17, was incorrectly printed. It should have been "P = .044." PMID- 17842038 TI - Polish scientist not interned. PMID- 17842039 TI - Cryptography research and security. PMID- 17842040 TI - Saturn's Rings. PMID- 17842041 TI - Cancer and environment. PMID- 17842042 TI - Ocean research in hot water. PMID- 17842043 TI - Fast ion bombardment of ices and its astrophysical implications. AB - Ices such as water, carbon dioxide, and methane are now known to be pervasive constituents of the solar system and probably of the interstellar medium as well. Many of these ices and ice-covered surfaces are exposed to bombardment by the energetic ions of space. Laboratory experiments have been carried out to study the effects of such bombardment. Surprisingly efficient erosion of ice layers is associated with electronic excitation of the ices by the ions. These results are a challenge to an understanding of the physical processes involved and have implications for a number of astrophysical problems of current interest. PMID- 17842044 TI - Sharing credit for the nobel. PMID- 17842045 TI - NIOSH Backs Down on Portsmouth Study. PMID- 17842046 TI - IOM Votes Statement Against Nuclear War. PMID- 17842047 TI - The end of an accelerator named isabelle. PMID- 17842048 TI - Remembering the bomb, 40 years after. PMID- 17842049 TI - Physicists try to find order in chaos. PMID- 17842051 TI - Arctic division meeting. PMID- 17842050 TI - Two new routes to solar hydrogen. PMID- 17842052 TI - Capitol conference focuses on technologies for disabled people. PMID- 17842053 TI - Obituaries. PMID- 17842054 TI - Daedalus Discounted for AAAS Members. PMID- 17842055 TI - Recycled science. PMID- 17842056 TI - Carcinogens in the workplace. PMID- 17842057 TI - A barrier reef. PMID- 17842058 TI - Music and psychology. PMID- 17842059 TI - Metal-metal bonds. PMID- 17842060 TI - Termites: a potentially large source of atmospheric methane, carbon dioxide, and molecular hydrogen. AB - Termites may emit large quantities of methane, carbon dioxide, and molecular hydrogen into the atmosphere. Global annual emissions calculated from laboratory measurements could reach 1.5 x 10(14) grams of methane and 5 x 10(16) grams of carbon dioxide. As much as 2 x 10(14) grams of molecular hydrogen may also be produced. Field measurements of methane emissions from two termite nests in Guatemala corroborated the laboratory results. The largest emissions should occur in tropical areas disturbed by human activities. PMID- 17842061 TI - Tin and methyltin species in seawater: concentrations and fluxes. AB - The concentrations of tin and methyltin species in rivers, an estuary, and the surface and deep ocean generally are less than 50 picomoles of tin per liter. Estuarine profiles and river concentrations suggest that the dissolved riverine input of tin is only a minor source of this element to the oceans. Oceanic concentrations of inorganic tin decrease both with distance from land and with increasing depth from the surface, an indication of atmospheric transport to the surface ocean. Most of the contemporaneous eolian influx of tin to the oceans is anthropogenic. The vertical structure oftin concentrations in the northwestern Atlantic can be explained in terms of a model based on eolian input, advective processes, and removal of tin by particulate scavenging. PMID- 17842063 TI - Atmospheric trace gases: linear relation between concentration and time. PMID- 17842062 TI - Aggressive signal in "courtship" chirps of a gregarious cricket. AB - Unlike other known species of crickets, Amphiacusta maya in Central America mates in groups. Experimentally silenced males experience reduced mating success, not owing to decreased receptivity by females, but owing to increased time spent fighting with other males that persistently interrupt silent courtships. Thus, the data indicate that "courtship" chirping functions as a warning to other males, rather than as a signal to females. PMID- 17842064 TI - Naloxone and ischemic neurologic deficits in the gerbil: is there an effect? PMID- 17842066 TI - Publications Received. PMID- 17842065 TI - Chemical Corps Medical Laboratories. PMID- 17842067 TI - Meetings and Conferences. PMID- 17842068 TI - The Occurrence of Hydrocarbons in Recent Sediments from the Gulf of Mexico. PMID- 17842069 TI - Dangers Confronting American Science. PMID- 17842070 TI - Concerning the Ability of Homing Pigeons to Discriminate Patterns of Polarized Light. PMID- 17842072 TI - The Road to Survival. PMID- 17842071 TI - Psychological vs. Bacteriological Warfare. PMID- 17842073 TI - Fluorometric Determination of N1-Methylniacinamide. PMID- 17842075 TI - Letters to the editor. PMID- 17842074 TI - Letters to the editor. PMID- 17842076 TI - Letters to the editor. PMID- 17842077 TI - Preventing obsolescence. PMID- 17842078 TI - Letters to the editor. PMID- 17842079 TI - Letters to the editor. PMID- 17842080 TI - More on extrasensory induction of brain waves. PMID- 17842081 TI - Game theory. PMID- 17842082 TI - Letters to the editor. PMID- 17842084 TI - Priority. PMID- 17842083 TI - Parlor Game and Boop-Boop-a-Doop. PMID- 17842085 TI - Dynamics of interplanetary dust. PMID- 17842086 TI - Elementary science: a new scheme of instruction. PMID- 17842087 TI - Scientists and civil defense: dialogue at berkeley. PMID- 17842088 TI - Nuclear weapons: nonproliferation and test-ban talks to be resumed. PMID- 17842089 TI - Mobility of the hydrated electron. AB - The transient change in conductivity in diluted barium hydroxide solutions during and immediately after irradiation with single pulses of electrons from a 15 million-electron-volt linear accelerator was measured. Ionic mobility of the radiation-produced hydrated electrons was 1.84 x 10(-3)cm(-2) volt(-1) sec(-1) +/ 10 percent. This value corresponds to a diffusion constant of 4.75 x 10(-5) cm(2) sec(-1). PMID- 17842090 TI - A search for intergalactic hydrogen in the virgo cluster. AB - A fixed-horn antenna having a beam 10 degrees by 10 degrees , and a switched-load radiometer with traveling-wave-maser preamplifier were used to observe the 21-cm spectrum of the Virgo cluster of galaxies. An upper limit to the antenna temperature is 0.024 degrees K relative to regions outside the cluster with filters whose width is 2 Mc/sec. If the excitation temperature of the intergalactic hydrogen is enough greater than the background continuum radiation so that absorption can be ignored, and if the velocity spectrum is that defined by the galaxies, the density of optically thin neutral hydrogen in the cluster does not exceed that outside of the cluster by an amount that gives 5.6 x 10(12) solar masses in the cluster. PMID- 17842091 TI - Gravitational lens effect: an observational test. AB - The large proper motion of the nearby star 40 Eridani-A will pass a distant star in 1988. It should be possible to observe the gravitational lens effect of this eclipse by existing photoelectric methods. PMID- 17842092 TI - Wormlike fossil from the pennsylvanian of illinois. AB - Tullimonstrum gregarium was a common, possibly marine, invertebrate in certain shallow, offshore waters of northern Illinois during the Middle Pennsylvanian. It had a flexible proboscis armed with teeth; a mobile tail; and a curious transverse bar behind the head, bearing a pair of round, external organs. PMID- 17842094 TI - Chromosome Complement: A Fertile Hybrid between Equus priewalskii and Equus caballus. AB - At the Zoological Garden of Antwerp it has been proved that when Equus prjewalskii is crossed with E. caballus the offspring is fertile. As expected, its diploid chromosome number is 65. The morphological differences between the parental and the offspring karyotypes are not great; therefore, meiosis in the hybrid was successfully achieved. PMID- 17842093 TI - Tungsten diboride: preparation and structure. AB - A new tungsten boride has been prepared and has been assigned the formula WB(2). The assignment is based on comparison of the x-ray diffraction data of this boride with those of diborides of the AlB(2) type structure. Values of a(0) = 3.02 and c(0) = 3.05 were calculated for a hexagonal unit cell. PMID- 17842095 TI - Photoperiodic, induction of senescence in xanthium plants. AB - Xanthium plants placed under photoinductive conditions were accelerated in their senescence whether or not the plants had a capacity to produce flowers and fruits. Thus, the role of the mobilization influence of these organs on the senescence of certain monocarpic plants can be questioned. PMID- 17842096 TI - Myristicin in cigarette smoke. AB - The pharmacologically active aromatic ether, myristicin, was isolated from the smoke of commercial cigarettes. The compound was identified by spectrometry (infrared, ultraviolet, and mass) and gas chromatography. The amount of myristicin in smoke is relatively low, and its contribution, if any, to the physiological action of cigarette smoke is unknowvn. PMID- 17842097 TI - Gibberellin and growth in isolated wheat embryos. AB - Gibberellic acid promoted elongation growth in the coleoptiles and leaves of embryos from gamma-irradiated wheat grains whether the embryos were isolated or attached to the endosperm. Thus gibberellic acid affected this growth directly rather than indirectly through an effect upon endosperm. However, root growth was promoted by gibberellic acid only on embryos attached to endosperm, suggesting an indirect effect of gibberellic acid upon growth. PMID- 17842098 TI - Tobacco seedlings: damage by excessive nitrogen lessened by added phosphorus. AB - Concentrations of nitrogen (as ammonium nitrate) of 50 kilo-grams per hectare and greater are toxic to tobacco seedlings; symptoms are poor growth and white leaves. The leaves have markedly less chlorophylls (especially chlorophyll a) and more carotene and xanthophyll than seedlings grown in media low in nitrogen. These ill eflects are aggravated by short supply of phosphorus; they can be counteracted by more liberal supply of phosphorus. PMID- 17842099 TI - Abscisin II: Inhibitory Effect on Flower Induction in a Long-Day Plant. AB - The flowering response by plants of Lolium temulentum after exposure to 1 long day was significantly reduced by single applications of abscisin 11 to the leaves or near the shoot apex. The time course of this inhibitory effect suggests that abscisin 11 acts at the shoot apex when the floral stimulus arrives there. PMID- 17842100 TI - Quaternary stratigraphy. PMID- 17842101 TI - Ethological study of behavior. PMID- 17842102 TI - Thermal analysis. PMID- 17842103 TI - Forthcoming events. PMID- 17842104 TI - Ehrenwald is correct. PMID- 17842105 TI - Einstein on ESP. PMID- 17842106 TI - Cryptology and national security. PMID- 17842107 TI - Investigating paranormal claims. PMID- 17842108 TI - West german breeder cost. PMID- 17842109 TI - Mars and Earth: origin and abundance of volatiles. AB - Mars, like Earth, may have received its volatiles in the final stages of accretion, as a veneer of volatile-rich material similar to C3V carbonaceous chondrites. The high (40)Ar/(36)Ar ratio and low (36)Ar abundance on Mars, compared to data for other differentiated planets, suggest that Mars is depleted in volatiles relative to Earth-by a factor of 1.7 for K and 14 other moderately volatile elements and by a factor of 35 for (36)Ar and 15 other highly volatile elements. Using these two scaling factors, we have predicted martian abundances of 31 elements from terrestrial abundances. Comparison with the observed (36)Ar abundance suggests that outgassing on Mars has been about four times less complete than on Earth. Various predictions of the model can be checked against observation. The initial abundance of N, prior to escape, was about ten times the present value of 0.62 ppb, in good agreement with an independent estimate based on the observed enhancement in the martian (15)N/(14)N ratio (78,79). The initial water content corresponds to a 9-m layer, close to the value of >/=13 m inferred from the lack of an (18)O/(16)O fractionation (75). The predicted crustal Cl/S ratio of 0.23 agrees exactly with the value measured for martian dust (67); we estimate the thickness of this dust layer to be about 70 m. The predicted surface abundance of carbon, 290 g/cm(2), is 70 times greater than the atmospheric CO(2) value, but the CaCO(3) content inferred for martian dust (67) could account for at least one-quarter of the predicted value. The past atmospheric pressure, prior to formation of carbonates, could have been as high as 140 mbar, and possibly even 500 mbar. Finally, the predicted (129)Xe/(132)Xe ratio of 2.96 agrees fairly well with the observed value of 2.5(+2)(-1) (85). From the limited data available thus far, a curious dichotomy seems to be emerging among differentiated planets in the inner solar system. Two large planets (Earth and Venus) are fairly rich in volatiles, whereas three small planets (Mars, the moon, and the eucrite parent body-presumably the asteroid 4 Vesta) are poorer in volatiles by at least an order of magnitude. None of the obvious mechanisms seems capable of explaining this trend, and so we can only speculate that the same mechanism that stunted the growth of the smaller bodies prevented them from collecting their share of volatiles. But why then did the parent bodies of the chondrites and shergottites fare so much better? One of the driving forces behind the exploration of the solar system has always been the realization that these studies can provide essential clues to the intricate network of puzzles associated with the origin of life and its prevalence in the universe. In our own immediate neighborhood, Mars has always seemed to be the planet most likely to harbor extraterrestrial life, so the environment we have found in the vicinity of the two Viking landers is rather disappointing in this context. But the perspective we have gained through the present investigation suggests that this is not a necessary condition for planets at the distance of Mars from a solar-type central star. In other words, if it turns out that Mars is completely devoid of life, this does not mean that the zones around stars in which habitable planets can exist are much narrower than has been thought (114). Suppose Mars had been a larger planet-the size of Earth or Venus-and therefore had accumulated a thicker veneer and had also developed global tectonic activity on the scale exhibited by Earth. A much larger volatile reservoir would now be available, there would be repeated opportunities for tapping that reservoir, and the increased gravitational field would limit escape from the upper atmosphere. Such a planet could have produced and maintained a much thicker atmosphere, which should have permitted at least an intermittently clement climate to exist. How different would such a planet be from the present Mars? Could a stable, warm climate be maintained? It seems conceivable that an increase in the size of Mars might have compensated for its greater distance from the sun and that the life zone around our star would have been enlarged accordingly. PMID- 17842110 TI - Landsat, computers, and development projects. AB - Data provided by earth-orbiting satellites and analyzed through specific computer techniques are rapidly providing policy-makers around the world with new information on the location and extent of their countries' renewable and nonrenewable resources. Development projects utilizing remote sensing technology are being supported, for example, by the Inter-American Development Bank, the World Bank, and other international funding agencies. The Inter-American Development Bank is financing a natural resources inventory of five countries in Central America, and this will require the application of remote sensing in the analysis of 33 Landsat images covering the area. Although the Landsat program remains experimental in nature, studies pertaining to its follow-on aspects will ensure continuation of the program so that developed and developing countries will be able to maintain better control of the management of their natural resources. PMID- 17842112 TI - Academics urged to join sun day observance. PMID- 17842111 TI - Texas power companies converting from natural gas to coal, lignite. PMID- 17842113 TI - Senate Panel Wants OSTP to Take the Long View. PMID- 17842114 TI - CEQ Nominee Learns Judge Not, Lest Ye Be Judged. PMID- 17842115 TI - Alaska wilderness: congress debates resources "lock up". PMID- 17842116 TI - Cryptography meeting goes smoothly. PMID- 17842117 TI - High energy physics: a proliferation of quarks and lepton. PMID- 17842118 TI - New accelerators: cornell gets an electron storage ring. PMID- 17842119 TI - Neutron scattering: new look at biological molecules. PMID- 17842120 TI - AAAS Seminars Examine National Energy Plan, Indian Resources. PMID- 17842121 TI - AAAS People. PMID- 17842123 TI - CSFR to Hear Azbel. PMID- 17842122 TI - Annual meeting notes. PMID- 17842124 TI - NGO's Review Roles in 1979 U.N. Conference. PMID- 17842125 TI - Program in marine science for precollege handicapped. PMID- 17842126 TI - For the library. PMID- 17842127 TI - AAAS and AISLE to Aid Maryland Legislature. PMID- 17842128 TI - Science and technology: new tools, new dimensions. PMID- 17842129 TI - Meeting information. PMID- 17842130 TI - Science and technology: new tools, new dimensions. PMID- 17842131 TI - The eugenics movement. PMID- 17842133 TI - Vertebrate structures. PMID- 17842132 TI - Membrane biology. PMID- 17842134 TI - Developmental biology. PMID- 17842135 TI - Atomic Chlorine and the Chlorine Monoxide Radical in the Stratosphere: Three in situ Observations. AB - Three simultaneous observations of atomic chlorine (Cl) and the chlorine monoxide radical (ClO) are reported which encompass the altitude interval between 25 and 45 kilometers. Together, Cl and ClO form a gas-phase catalytic cycle potentially capable of depleting stratospheric ozone. Observed Cl and C1O densities, although variable, imply that chlorine compounds constitute an important part of the stratospheric ozone budget. The results are compared with recent models of stratospheric photochemistry which have been used as a basis for predicting ozone depletion resulting from fluorocarbon release. PMID- 17842136 TI - Uranus: the rings are black. AB - An upper limit of 0.05 is established for the geometric albedo of the newly discovered rings of Uranus. In view of this very low albedo, the particles of the rings cannot be ice-covered as are those of rings A and B of Saturn. PMID- 17842137 TI - Winter intrusions of the loop current. AB - Sea-surface temperature data obtained from satellite and subsurface temperature data obtained from ships are used to determine the intrusion of the The Loop Current extended considerably farther to the north during the last three winters than has been observed previously. PMID- 17842138 TI - Carbon-14: direct detection at natural concentrations. AB - The (14)C atoms naturally present in a piece of 19th-century wood have been detected directly by means of a tandem Van de Graaff accelerator used as a high energy mass spectrometer. The (14)C ions were easily resolved from interfering ions with the use of a DeltaE-E detector telescope (this telescope consists of a pair of detectors; one of them measures the specific ionization, DeltaE, and the sum of the signals from both detectors gives the total energy for each ion, ET). The technique offers a number of practical advantages. PMID- 17842139 TI - Radiocarbon dating using electrostatic accelerators: negative ions provide the key. AB - Mass spectrometric methods have long been suggested as ways of measuring (14)C/(12)C ratios for carbon dating. One problem has been to distinguish between (14)N and (14)C. With negative ions and a tandem electrostatic accelerator, the (14)N background is virtually absent and fewer than three (14)C atoms in 10(16) atoms of (12)C have been easily measured. PMID- 17842140 TI - Selective vocal learning in a sparrow. AB - Male swamp sparrows learn their songs; they fail to learn songs of the sympatric song sparrow. Syllables from tape recordings of both species of sparrow were spliced into an array of swamp sparrow-like and song sparrow-like temporal patterns. Swamp sparrows learned only those songs made of swamp sparrow syllables. They did so irrespective of whether the temporal pattern was swamp sparrow-like or song sparrow-like. Selectivity was retained by birds reared in total isolation from adult conspecific sounds. PMID- 17842141 TI - Retinoyl complexes in batten disease. PMID- 17842143 TI - Letter to the editor. PMID- 17842142 TI - Letter to the editor. PMID- 17842145 TI - Letter to the editor. PMID- 17842144 TI - Letter to the editor. PMID- 17842146 TI - Creationism and evolutionism. PMID- 17842148 TI - Letter to the editor. PMID- 17842147 TI - Letter to the editor. PMID- 17842149 TI - Letter to the editor. PMID- 17842150 TI - DDT in British Rain. PMID- 17842151 TI - Joint effort. PMID- 17842152 TI - Humane technology. PMID- 17842153 TI - Contacts with Earth Scientists in the People's Republic of China: Geological tasks are popular; collective participation and relevance to current problems are emphasized. PMID- 17842154 TI - Darwin and Evolutionary Psychology: Darwin initiated a radically new way of studying behavior. PMID- 17842155 TI - The Discovery of America: The first Americans may have swept the Western Hemisphere and decimated its fauna within 1000 years. AB - I propose a new scenario for the discovery of America. By analogy with other successful animal invasions, one may assume that the discovery of the New World triggered a human population explosion. The invading hunters attained their highest population density along a front that swept from Canada to the Gulf of Mexico in 350 years, and on to the tip of South America in roughly 1000 years. A sharp drop in human population soon followed as major prey animals declined to extinction. Possible values for the model include an average frontal depth of 160 kilometers, an average population density of 0.4 person per square kilometer on the front and of 0.04 person per square kilometer behind the front, and an average rate of frontal advance of 16 kilometers per year. For the first two centuries the maximum rate of growth may have equaled the historic maximum of 3.4 percent annually. During the episode of faunal extinctions, the population of North America need not have exceeded 600,000 people at any one time. The model generates a population sufficiently large to overkill a biomass of Pleistocene large animals averaging 9 metric tons per square kilometer (50 animal units per section) or 2.3 x 10(8) metric tons in the hemisphere. It requires that on the front one person in four destroy one animal unit (450 kilograms) per week, or 26 percent of the biomass of an average section in 1 year in any one region. Extinction would occur within a decade. There was insufficient time for the fauna to learn defensive behaviors, or for more than a few kill sites to be buried and preserved for the archeologist. Should the model survive future findings, it will mean that the extinction chronology of the Pleistocene megafauna can be used to map the spread of Homo sapiens throughout the New World. PMID- 17842156 TI - Request for Proposals and Universities: The issues surrounding contract solicitation are discussed and recommendations for improvement are made. PMID- 17842157 TI - Alaskan oil: court ruling revives Canada pipeline issue. PMID- 17842158 TI - SIPI Takes Over as Publisher of Environment Magazine. PMID- 17842159 TI - Altered States of consciousness: mind researchers meet to discuss exploration and mapping of "inner space". PMID- 17842160 TI - European Space Program: It's Half-Speed Ahead. PMID- 17842161 TI - NIH Advisors Advised Penury Is Nigh. PMID- 17842162 TI - U.S.-Chinese Science: Who's in Charge Here? PMID- 17842163 TI - X-ray Astronomy (II): A New Breed of Pulsars. PMID- 17842164 TI - Venus: new microwave measurements show no atmospheric water vapor. AB - Two sets of passive radio observations of Venus-measurements of the spectrum of the disk temperature near the 1-centimeter wavelength, and interferometric measurements of the planetary limb darkening at the 1.35-centimeter water vapor resonance-show no evidence of water vapor in the lower atmosphere of Venus. The upper limit of 2 x 10(-3) for the mixing ratio of water vapor is substantially less than the amounts derived from the Venera space probes (0.5 x 10(-2) to 2.5 x 10(-2)). This amount of water vapor cannot produce dense clouds, and it is doubtful that it may contribute significantly to a greenhouse effect. PMID- 17842165 TI - Polar wandering on Mars? AB - Polar wandering during the past 10(8) years may be recorded by unique quasi circular structures in the polar regions of Mars. Polar wandering on Mars is likely if deep convection is involved in the origin of the very large constructional volcanic features located near the equator. The magnitude of the nonhydrostatic low order components of the gravity field and their correlation with the equatorial volcanic features may be additional evidence of deep convection and associated polar wandering. PMID- 17842167 TI - Trilobite Eyes: Calcified Lenses in vivo. AB - The corneal lenses preserved in the eyes of some of the Paleozoic trilobites (Arthropoda) are constructed of calcite that is crystallographically oriented to behave like glass. The calcareous lenses are capable of forming inverted images over a large depth of field and must have been present in the living trilobites. PMID- 17842166 TI - Hormonal regulation of growth in unfertilized cotton ovules. AB - Exogenous plant growth regulators can substitute for pollination, fertilization, and subsequent embryo development in cotton. Isolated, unfertilized, immature ovules enlarge in the presence of kinetin, and both enlarge and produce fibers in the presence of indoleacetic acid or gibberellic acid or both. An extract of germinating cotton pollen qualitatively mimics the effect of exogenous hormones. PMID- 17842168 TI - The sea and its resources. PMID- 17842170 TI - Hurricanes. PMID- 17842169 TI - Environmental health in the americas. PMID- 17842171 TI - Gordon research conferences. PMID- 17842172 TI - MICROORGANISMS OF THE SOIL. PMID- 17842173 TI - PLANT FOOD IN RELATION TO SOIL FERTILITY. PMID- 17842174 TI - THE FIFTH INTERNATIONAL CONGRESS OF MATHEMATICIANS. PMID- 17842175 TI - THE NEW ENGLAND GEOLOGICAL EXCURSION. PMID- 17842176 TI - THE PAGEANT AT MOUNT HOLYOKE COLLEGE. PMID- 17842177 TI - THE FIRST USE OF TRINIDAD PITCH FOR ROAD MAKING. PMID- 17842179 TI - ANTAGONISTIC ACTION OF ELECTROLYTES AND PERMEABILITY OF THE CELL MEMBRANE. PMID- 17842178 TI - THE "WILLIAMS' PROCESS" OF PHOTOGRAPHY. PMID- 17842180 TI - VITAL STAINING OF CHROMOSOMES AND THE FUNCTION AND STRUCTURE OF THE NUCLEUS. PMID- 17842181 TI - EXPERIMENTS WITH DESICCATED THYROID, THYMUS AND SUPRARENALS. PMID- 17842182 TI - NOTICE OF NEWLY DISCOVERED EURYPTERIDS IN NEBRASKA. PMID- 17842183 TI - SOME NECESSARY CHANGES IN CEPHALOPOD NOMENCLATURE. PMID- 17842184 TI - The Transuranium Elements. PMID- 17842185 TI - Carl Louis August Schmidt 1885-1946. PMID- 17842186 TI - Unequal Distribution of Diffusible Nonelectrolytes Across a Membrane. PMID- 17842187 TI - The Use of Cytochrome C in Combating Tissue Anoxia. PMID- 17842188 TI - An Improved Helmet for Breathing Oxygen or Other Gases. PMID- 17842189 TI - Reciprocal Sensitivities of Staphylococcus aureus to Streptomycin, Streptothricin, and Penicillin. PMID- 17842190 TI - In Vitro Action of Monopyridine Iodine (I) p-Nitrobenzoate Against Ringworm Fungi. PMID- 17842191 TI - Effect of 2,4-Dichlorophenoxyacetic Acid on the Development of Anjou Pear Scald. PMID- 17842192 TI - On Eugen Fischer. PMID- 17842193 TI - Surface Measurements of Radioactive Phosphorus in Breast Tumors as a Possible Diagnostic Method. PMID- 17842195 TI - Comments on "A Relativistic Misconception". PMID- 17842194 TI - Comments on "A Relativistic Misconception". PMID- 17842196 TI - Correction on the Nomenclature of Human Plasmodium. AB - In the nomenclatorial and zoological confusion in the names for the human malaria parasites (Sabrosky and Usinger. Science, 1944, 100, 190-192; Beltran. Gaceta Med. Mexico, 1944, 74, 61-74), one further point has been discovered. It has usually been considered that there were only two different proposals involving malariae as a new specific name-Oscillaria malariae Laveran, 1881, and Haemamoeba malariae Feletti and Grassi, 1890. Actually it now appears that there were three! PMID- 17842197 TI - Use of Shorthand by Scientists. PMID- 17842198 TI - Comments on "A Relativistic Misconception". PMID- 17842199 TI - Radioactive Hydrocarbons. PMID- 17842200 TI - Technical Decisions in Technical Hands. PMID- 17842201 TI - Botanical Prospecting for Ore Deposits. PMID- 17842202 TI - The Academic Scientist, 1940-1960. PMID- 17842203 TI - Science and Politics: AMA Attacked for Use of Disputed Survey in "Medicare" Lobbying. PMID- 17842204 TI - The Rump Session: It Does What Is Absolutely Necessary, But Very Little More. PMID- 17842205 TI - Brode Resigns as State Department Science Adviser; Whitman Named Successor. PMID- 17842206 TI - Geneva Talks Adjourn. PMID- 17842207 TI - Washington University Group Analyzes Project Plowshare for St. Louis Citizens' Committee. PMID- 17842208 TI - New List of Paperbound Science Books Prepared by AAAS Library Program. PMID- 17842209 TI - Anaerobiosis in Marine Sandy Beaches. AB - Organisms living at depths greater than 5 to 10 cm in marine beaches composed of fine sand are completely anaerobic whenever their particular section of beach is covered by water. Anaerobic conditions are continuous if the slope of the beach is slight enough so that capillary forces keep the sand saturated with water even at low tide. PMID- 17842211 TI - Forthcoming Events. PMID- 17842210 TI - Dehydrogenase Activities in Dystrophic Mice. AB - The levels of activity of glucose-6-phosphate dehydrogenase, isocitric dehydrogenase, glutathione reductase, lactic dehydrogenase, and a glycerophosphate dehydrogenase have been studied in the gastrocnemius muscle of mice with "dystrophia muscularis." The activity of enzymes requiring triphosphopyridine nucleotide as a cofactor is increased relative to the control littermates, whereas the activity of those enzymes requiring diphosphopyridine nucleotide is decreased. PMID- 17842212 TI - Letters to the Editor. PMID- 17842213 TI - Letters to the Editor. PMID- 17842214 TI - Life of Scientific Publications. PMID- 17842215 TI - Sweating in Man. PMID- 17842216 TI - Stern's View of Lewis H. Morgan. PMID- 17842217 TI - SCIENCE NEWS. PMID- 17842218 TI - SCIENCE AND PROSPERITY. PMID- 17842219 TI - THE MOTION OF GLACIERS. PMID- 17842220 TI - GRANTS IN AID OF RESEARCH FOR 1935. PMID- 17842222 TI - ON THE GREAT ABUNDANCE OF THE BLACK WIDOW SPIDER. PMID- 17842221 TI - FRESHWATER MEDUSAE NEAR BUFFALO. PMID- 17842223 TI - ON THE CULTIVATION OF SEVEN SPECIES OF TRYPANOSOMES IN VITRO. PMID- 17842225 TI - PURE CULTURES OF PARAMECIUM. PMID- 17842224 TI - AN ARTIFICIAL SYMBIOSIS. PMID- 17842226 TI - DETAILED SURVEYS OF SUBMARINE CANYONS. PMID- 17842227 TI - ACCESSORY HEARTS IN THE OYSTER. PMID- 17842228 TI - IS THE COLOR OF THE NATURAL RUBY DUE TO IRON? PMID- 17842229 TI - THE MOLECULAR WEIGHT OF THYROGLOBULIN. PMID- 17842230 TI - Reserve Forces Act of 1955. PMID- 17842231 TI - Radioactive Fallout from Bomb Clouds. PMID- 17842232 TI - J. P. Marble, Research Geochemist. PMID- 17842234 TI - Tetrapod Limb. PMID- 17842233 TI - News of Science. PMID- 17842235 TI - Miscellaneous Publicatons. PMID- 17842237 TI - Scientific Meetings. PMID- 17842238 TI - Liberal arts colleges and science education. PMID- 17842240 TI - Sex and gender. PMID- 17842239 TI - Sex and gender. PMID- 17842241 TI - Universities defending themselves in Japan. PMID- 17842242 TI - Ethics of AIDS study. PMID- 17842243 TI - Thyroid protection. PMID- 17842244 TI - Meeting briefs: neuroscientists seek answers to brain function and disease. PMID- 17842245 TI - Response: mechanisms of punctuated evolution. PMID- 17842246 TI - Dating the cenancester of organisms. PMID- 17842247 TI - Dating the cenancester of organisms. PMID- 17842248 TI - Response: dating the cenancester of organisms. PMID- 17842249 TI - THE INFLUENCE OF THE MATERIAL OF WIND-INSTRUMENTS ON THE TONE QUALITY. PMID- 17842251 TI - THE SEVENTH INTERNATIONAL CONGRESS OF APPLIED CHEMISTRY. PMID- 17842250 TI - REPORT OF COMMITTEE ON STANDARDS OF AMERICAN UNIVERSITIES. PMID- 17842252 TI - DARWIN ANNIVERSARY COMMITTEE. PMID- 17842253 TI - THE COLUMBIA UNIVERSITY DARWIN LECTURES. PMID- 17842254 TI - GRAY'S NEW MANUAL OF BOTANY. PMID- 17842255 TI - CONVOCATION WEEK. PMID- 17842256 TI - DISTRIBUTION OF THE NOBEL PRIZE. PMID- 17842257 TI - BOTANICAL NOTES. PMID- 17842258 TI - ANTHROPOLOGY AT THE BRITISH ASSOCIATION. PMID- 17842259 TI - THE PRESENCE OF WATER VAPOR IN THE ATMOSPHERE OF MARS DEMONSTRATED BY QUANTITATIVE MEASUREMENTS. PMID- 17842260 TI - THE SELACHIANS ADMITTED AS A DISTINCT CLASS. PMID- 17842261 TI - SEVENTH ANNUAL MEETING OF THE AMERICAN SOCIETY OF VERTEBRATE PALEONTOLOGISTS. PMID- 17842262 TI - THE AMERICAN CHEMICAL SOCIETY NEW YORK SECTION. PMID- 17842263 TI - THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE. PMID- 17842265 TI - Meetings & Conferences. PMID- 17842264 TI - A Problem for Educators. PMID- 17842266 TI - Chicago Radiocarbon Dates V. PMID- 17842267 TI - Miscellaneous Publications. PMID- 17842268 TI - Highway travel subsidies. PMID- 17842269 TI - Letter to the editor. PMID- 17842270 TI - Letter to the editor. PMID- 17842271 TI - ORSA and the ABM. PMID- 17842272 TI - An "abundance of fish". PMID- 17842273 TI - Multinational journals. PMID- 17842274 TI - Collective bargaining on campus. PMID- 17842275 TI - Nimbus IV View of the Major Structural Features of Alaska. AB - Notwithstanding the relatively low degree of ground resolution, many of the major structural features of Alaska can be identified on the Nimbus IV IDCS image, exposed at an altitude of 600 nautical miles (1100 km). In addition, linears of regional extent that may be structurally controlled can be seen, many of which have not yet been recognized in surface mapping. The synoptic view provided by the image brings into focus an orthogonal set of fractures trending north northeast and east-south-east and not heretofore apparent in regional maps of Alaska. This orthogonal fracture set may reflect a conjugate set of fractures within the crust, which has exerted significant control over the geologic history of the state. Increased resolution in other images from space platforms, such as the resolution of 200 to 650 feet (60 to 200 m) planned for the satellite television cameras of the ERTS program (20), will permit the discernment of finer detail and a greater accuracy in identifying and locating geologic features. PMID- 17842277 TI - NSF Appointment: Science Elite, White House Reward Favorite Son. PMID- 17842276 TI - Measurement structures and psychological laws. AB - Empirical laws psychology may be based on physical measurements (for example, voltages, times), counting, ordering, or just classifying. It is a pointless, though widespread practice to use a physical measure or a count as a "definition" of a psychological variable; this practice obscures the fact that all one has done is measured a physical variable, or counted. What is important are the empirical laws that are established by use of such quantitative or qualitative observations. Some kinds of empirical relations and laws yield measurement structures, akin to the qualitative structures underlying fundamental measurement in physics. Measurement structures are empirical structures that can be described most simply by introduction of a new numerical function; such a function is a new measure, and is typically interpreted as measuring some particular psychological variable Measurement structures, formulated abstractly, sometimes provide valuable tools for formulating new empirical hypotheses to be tested; but in many instances, other kinds of theory may be more appropriate. The main focus of research ought always to be the discovery of simple laws; these may or may not lead to new measures. PMID- 17842278 TI - Briefing. PMID- 17842279 TI - Blood banking: tangled system resists swift change. PMID- 17842280 TI - French science policy: problems of "leveling off". PMID- 17842281 TI - Astronomy: TV Cameras Are Replacing Photographic Plates. PMID- 17842282 TI - New journals received. PMID- 17842283 TI - Red sea hot brine area: revisited. AB - A return expedition to the hot brine area of the Red Sea in 1971 found that the temperature of the brine had increased, indicating that the process that formed the underlying deposits rich in heavy metals is still occurring. About 0.346 cubic kilometers of water having a minimum temperature of 104 degrees C has been added over the last 52 months. Calculations suggest that this water may have come from a relatively shallow depth; this result coupled with the fact that fracture zones are found north and south of the brine area indicates a relatively local source for the brine, rather than the Strait of Bab el Mandeb, as previously suggested. PMID- 17842284 TI - Magnetic noise preceding the august 1971 summit eruption of kilauea volcano. AB - During the course of an electromagnetic survey about Kilauea Volcano in Hawaii, an unusual amount of low-frequency noise was observed at one recording location. Several weeks later an eruption occurred very close to this site. The high noise level appeared to be associated in some way with the impending eruption. PMID- 17842285 TI - Buried caldera of mauna kea volcano, hawaii. AB - An elliptical caldera (2.1 by 2.8 kilometers) at the summit of Mauna Kea volcano is inferred to lie buried beneath hawaiite lava flows and pyroclastic cones at an altitude of approximately 3850 meters. Stratigraphic relationships indicate that hawaiite eruptions began before a pre-Wisconsin period of ice-cap glaciation and that the crest of the mountain attained its present altitude and gross form during a glaciation of probable Early Wisconsin age. PMID- 17842286 TI - Amino Acid composition of planktonic foraminifera: a paleobiochemical approach to evolution. AB - A unique, species-specific amino acid composition is identified with each of 16 species of planktonic Foraminifera isolated from the tops of deep-sea sediment cores. This amino acid pattern appears to directly reflect the genotype. The total amino acid content ranges from 2.0 to 4.2 micromoles per gram of calcified tissue or 0.02 to 0.04 percent by weight. Analyses of two Early Miocene species indicate that characteristic compositional differences are sufficiently well preserved over geologic time to determine phylogenetic affinities among extinct species living at least 18 million years ago. PMID- 17842287 TI - High-temperature superconductors, the first ternary system. AB - A new system of high-temperature superconductors is reported. The compounds, Mo(6 - x)A(x)S(6) where A is Cu, Zn, Mg, Ag, Cd, Sn, or Pb, are rhombohedral with a approximately 6.5 angstroms and approximately 90 degrees . The transition temperatures range from approximately 2.5 degrees K for the Cd compound to approximately 13 degrees K for the Pb compound. PMID- 17842288 TI - Sex Pheromones of Summer Fruit Tortrix Moth Adoxophyes orana: Two Synergistic Isomers. AB - Both cis-9-and cis-11-tetradecenyl acetate were isolated from 2500 virgin females of the summer fruit tortrix moth Adoxophyes orana (F.v.R.) by gel permeation, column chromatography on silica gel, and gas chromatography. Their chemical, physical, and biological properties were identical to those of the synthetic compounds. In contrast to the single compounds, mixtures of these pheromones were highly active in laboratory and field tests. Catches, in traps, with the pheromone mixture were comparable to those obtained when live females were used as bait. This is the first example of a member of the lepidoptera in which the presence of two isomers is an absolute requirement for activity in laboratory and in field experiments. PMID- 17842290 TI - THE LIVING GLOBE. PMID- 17842289 TI - Silk moth eclosion: hormonal triggering of a centrally programmed pattern of behavior. AB - The emergence of the adult cecropia silk moth from the pupal skin involves a stereotyped series of abdominal movements-the pre-eclosion behavior. This behavior, triggered by a neurosecretory hormone, consists of three phases that are characterized by the relative frequency and pattern of movements. Electrical recordings from a nerve cord with severed peripheral nerves demonstrate that the pre-eclosion behavior is prepatterned in the abdominal ganglia. In response to the hormone, the entire 1.25-hour behavioral program can be activated and "read off" in the absence of sensory feedback. PMID- 17842291 TI - THE BORN THEORY OF THE ELECTRON. PMID- 17842293 TI - THE FIRST SCHOOL OF CHEMISTRY. PMID- 17842292 TI - THE QUESTION OF WILDLIFE DESTRUCTION BY THE AUTOMOBILE. PMID- 17842294 TI - IS A PACEMAKER INVOLVED IN SYNCHRONOUS FLASHING OF FIREFLIES? PMID- 17842295 TI - BACTERIAL CONTENT OF THE AIR AT HIGH ALTITUDES. PMID- 17842296 TI - ON THE NATURE OF FILTERABLE VIRUSES. PMID- 17842297 TI - A SIMPLE METHOD OF DETERMINING AREAS IN MICROPHOTOGRAPHS. PMID- 17842299 TI - SCIENCE NEWS. PMID- 17842298 TI - A METHOD OF PREPARING SKELETONS OF SMALL VERTEBRATES. PMID- 17842300 TI - HONOR SOCIETIES. PMID- 17842301 TI - THE ELECTRON AND RADIATION. PMID- 17842302 TI - ENVELOPING MEMBRANES OF ECHINODERM OVA. PMID- 17842303 TI - A FOSSIL MAMMAL WITH UNBORN TWINS. PMID- 17842305 TI - USEFUL GREAT TOES. PMID- 17842304 TI - NOTE ON HAEMOGLOBIN. PMID- 17842306 TI - BABYLONIAN MATHEMATICS. PMID- 17842308 TI - THE CAPNOMETER, AN INSTRUMENT FOR THE MEASUREMENT OF AIR POLLUTION. PMID- 17842307 TI - A SIMPLE SPOT-PLATE TEST FOR NITRATE NITROGEN IN SOIL AND OTHER EXTRACTS. PMID- 17842309 TI - A THEORY OF THE RING METHOD FOR THE DETERMINATION OF SURFACE TENSION. PMID- 17842310 TI - PROLONGED EFFECT ON DIGITALIS PURPUREA OF EXPOSURE UNDER ULTRAVIOLET-TRANSMITTING GLASS. PMID- 17842311 TI - ENGINEERING SCIENCE BEFORE, DURING AND AFTER THE WAR. II. PMID- 17842312 TI - PHYSIOLOGICAL ISOLATION BY LOW TEMPERATURE IN BRYOPHYLLUM AND OTHER PLANTS. PMID- 17842314 TI - THE BRITISH ASSOCIATION. PMID- 17842313 TI - SNOW-ROLLERS. PMID- 17842315 TI - A WALL-SIDE MIRAGE. PMID- 17842317 TI - NEW FRUIT FUNGI FOUND ON THE CHICAGO MARKET. PMID- 17842316 TI - THE TRANS-ATLANTIC FLIGHTS AND OCEAN WEATHER MAPS. PMID- 17842318 TI - Science and the Race Problem. PMID- 17842319 TI - Letters to the Editor. PMID- 17842320 TI - Letters to the Editor. PMID- 17842321 TI - Letters to the Editor. PMID- 17842322 TI - Letters to the Editor. PMID- 17842323 TI - Letters to the Editor. PMID- 17842324 TI - Letters to the Editor. PMID- 17842326 TI - Letters to the Editor. PMID- 17842325 TI - Distribution of Research Funds. PMID- 17842327 TI - Letters to the Editor. PMID- 17842328 TI - Virus and Pseudocowpox Disease and disease. PMID- 17842329 TI - The Noble Gases. PMID- 17842331 TI - By Scientists for Scientists. PMID- 17842330 TI - Statistics Section Again. PMID- 17842332 TI - Pressure and Electronic Structure. PMID- 17842333 TI - Elliott Committee: Basic Research Fares Well as House Group Hears 38 on Federal Support of Science. PMID- 17842334 TI - AIdous Huxley: The Late Author Felt Scientists Tend To Search for Truth, Ignore Consequences. PMID- 17842335 TI - Kennedy's Assassination: Study Organized by Social Scientists. PMID- 17842336 TI - Congress: Hearings on Science Advisory Staff Reveals Interest, but No Strong Inside Demand. PMID- 17842337 TI - Forms of Sounds as Shown on an Oscilloscope by Roulette Figures. AB - It has been found that with an oscilloscope driven through a simple network of two resistors and two capacitors it is possible to produce recognizable pictures from speech sounds. These pictures thus become a natural phonetic alphabet, with which both standard pronunciation and the nuances of dialect and accent can be represented. While a given speech sound has certain invariant characteristics, it has also an overlay of accent, which can be represented in the alphabetic character. It is suggested that the technique may be useful in teaching deaf children to speak. PMID- 17842338 TI - Carbonate Rocks: Cleaning with Suspensions of Hydrogen-Ion Exchange Resin. AB - The surface of carbonate rocks may be cleaned by etching or polishing or both, with hydrogen-ion exchange resin. This treatment reveals details in texture and fossil morphology so clearly that thin sections may be often dispensed with. Of four cleaning methods, (i) allowing resin to settle around the sample, (ii) stirring with a magnetic stirrer, (iii) agitating with an ultrasonic generator, and (iv) directing a jet stream at the sample, the first method was best for large specimens and the second method was best for well cuttings and chips. PMID- 17842339 TI - Fresh Water: Temperature of Maximum Density Calculated from Compressibility. AB - Measurement of sonic velocities in water provides an accurate method for determining the equation of state for water. A simple equation of state for fresh water yields the temperature of maximum density as a function of pressure. PMID- 17842341 TI - Juvenile Hormone Activity: Effects of Isoprenoid and Straight-Chain Alcohols on Insects. AB - A wide variety of alcohols, applied topically or injected into pupae of the yellow mealworm, Tenebrio niolitor L., exhibit juvenile hormone activity. Inclulded among these comipounds are saturated and unsaturated alcohols with 8 to 15 carbon atoms, in straight-or branched-chains. Ether derivatives of several of these alcohols fuirther enhance the activity. PMID- 17842340 TI - Milk Analysis of the Kangaroo Rat, Dipodomys merriami. AB - The milk of Dipodomys merriami has an average water content of 50.42 percent, which is low compared with milk from other mammals. The fat content is about 23.48 percent. The significance of these values is discussed in terms of the animal's water balance. PMID- 17842342 TI - A Remarkably Reduced Vascular Plant in the United States. AB - A clone-forming thallus lacking sex organs and propagating by gemmae occurs on rocks and tree trunks in the Appalachian region from Georgia to Virginia, Ohio, and Kentucky. Although bryophytic in appearance, the thallus is identified here for the first time as a greatly reduced variety of the vascular plant known as "shoestring fern," Vittaria lineata (L.) J. E. Smith, or a closely related species. The normally dominant sporophytic phase of the life cycle has been eliminated and the plant exists only as a vegetative prothallus. PMID- 17842343 TI - Natural Plant Growth Regulators. PMID- 17842344 TI - Forthcoming Events. PMID- 17842345 TI - This week in science. PMID- 17842346 TI - A Paine-ful Start. PMID- 17842347 TI - Soil erosion estimates and costs. PMID- 17842348 TI - Response. PMID- 17842350 TI - Sciencescope. PMID- 17842349 TI - Corrections and clarifications. AB - In the Research News article "Extreme ultraviolet satellites open new view of the sky" by Donald Goldsmith (14 Apr., p. 202), astronomer Stuart Bowyer was incorrectly identified as the director of the University of California, Berkeley's Center for Extreme Ultraviolet Astronomy. Bowyer was the founding director of the center and was succeeded by Roger Malina, who became acting director in 1994 and is now director. Malina is, with Bowyer, a principal investigator of the National Aeronautics and Space Administration's EUVE (Extreme Ultraviolet Explorer) mission. PMID- 17842351 TI - From Russia with love: u.s. Cloud data. PMID- 17842352 TI - Building a wall against toxic waste. PMID- 17842353 TI - Japan picks first centers of excellence. PMID- 17842354 TI - At quadrennial geophysics fest, Earth scientists think globally. PMID- 17842356 TI - Ocean crackup. PMID- 17842355 TI - Researchers build a secure plasma prison. PMID- 17842357 TI - Stop worrying and love the bomb. PMID- 17842358 TI - Blood woes in Canada. PMID- 17842359 TI - Deliberate Poisoning at NIH? PMID- 17842360 TI - Urban ozone control and atmospheric reactivity of organic gases. AB - Control strategies for urban ozone traditionally have been based on mass reductions in volatile organic compounds (VOCs). Studies show, however, that some organic gas species (such as alkanes and alcohols) form an order of magnitude less ozone than equal mass emissions of others (such as alkenes and aldehydes). Chemically detailed photochemical models are used to assess uncertainty and variability in reactivity quantification. VOC control strategies based on relative reactivity appear to be robust with respect to nationwide variations in environmental conditions and uncertainties in the atmospheric chemistry. Control of selective organic gas species on the basis of reactivity can offer cost savings over traditional strategies. PMID- 17842361 TI - Force fluctuations in bead packs. AB - Experimental observations and numerical simulations of the large force inhomogeneities present in stationary bead packs are presented. Forces much larger than the mean occurred but were exponentially rare. An exactly soluble model reproduced many aspects of the experiments and simulations. In this model, the fluctuations in the force distribution arise because of variations in the contact angles and the constraints imposed by the force balance on each bead in the pile. PMID- 17842362 TI - Total alignment of calcite at acidic polydiacetylene films: cooperativity at the organic-inorganic interface. AB - Biological matrices can direct the absolute alignment of inorganic crystals such as calcite. Cooperative effects at an organic-inorganic interface resulted in similar co-alignment of calcite at polymeric Langmuir-Schaefer films of 10,12 pentacosadiynoic acid (p-PDA). The films nucleated calcite at the (012) face, and the crystals were co-aligned with respect to the polymer's conjugated backbone. At the same time, the p-PDA alkyl side chains reorganized to optimize the stereochemical fit to the calcite structure, as visualized by changes in the optical spectrum of the polymer. These results indicate the kinds of interactions that may occur in biological systems where large arrays of crystals are co aligned. PMID- 17842363 TI - Direct Observation of Dislocation Core Structures in CdTe/GaAs(001). AB - A strategy is presented for determining sublattice polarity at defects in compound semiconductors. Core structures of 60-degree and Lomer dislocations in the CdTe/GaAs(001) system have been obtained by the application of maximum entropy analysis to Z-contrast images (Z is atomic number) obtained in a 300 kilovolt scanning transmission electron microscope. Sixty-degree dislocations were observed to be of the glide type, whereas in the case of Lomer dislocations, both a symmetric (Hornstra-like) core and an unexpected asymmetric structure made up of a fourfold ring were seen. PMID- 17842364 TI - Synthesis and application of modulated polymer gels. AB - A class of environmentally responsive materials based on the spatial modulation of the chemical nature of gels is proposed and demonstrated here. The modulation was achieved by limiting the interpenetration of part of one gel network with another gel network. The gels so produced have an internally heterogeneous or modulated structure. Three simple applications based on the modulated gels are described here: a bigel strip, a shape memory gel, and a gel "hand." The bigel strip bends almost to a circle in response to a temperature increase or an increase in solvent concentration. The shape memory gel changes its shape from a straight line to a pentagon to a quadrangle as the temperature increases. These transitions from one shape to another are reversible. The gel "hand" in water can grasp or release an object simply by an adjustment of the temperature. PMID- 17842366 TI - Vignettes: a feeling for reason. PMID- 17842365 TI - Rethinking objectives and telling the truth. PMID- 17842367 TI - Products & materials. PMID- 17842369 TI - Erratum. AB - Figure 1 in the report "Muscle fatigue and the role of transverse tubules" by C. P. Bianchi and S. Narayan (15 Jan., p. 296) was inadvertently transposed with figure 2 in the report "Sedimentation field flow fractionation of liposomes" by J. J. Kirkland et al. (p. 297). The figure legends are correct. PMID- 17842368 TI - Fixed amount awards. PMID- 17842370 TI - State involvement in science and technology. PMID- 17842371 TI - Positron tomography and nuclear magnetic resonance imaging. AB - Noninvasive imaging methods for medical diagnosis and biological investigations, have evolved from qualitative radiological techniques to quantitative methods of measuring biochemical and physiological processes in human body. In particular, new developments in emission tomography, nuclear magnetic resonance imaging, and in vivo spectroscopy offer new horizons for medical research and clinical activities. These methods and their potentials are reviewed and contrasted. PMID- 17842372 TI - Atlantic herring: stock discreteness and abundance. AB - The number of genetically distinct herring stocks is determined by the number of distinct, geographically stable larval retention areas. Spawning sites in these areas may be highly localized or dispersed. Absolute population size mostly depends on the retention area available to the density-dependent larval postlarval stage. Although the extreme seasonal range of spawning time shown by Atlantic herring is not fully accounted for by a new hypothesis, current theory is not supported by the hypothesis or by empirical data. The management implications are discussed. PMID- 17842374 TI - Technology transfer: new controls urged. PMID- 17842373 TI - Philip handler: his research. PMID- 17842375 TI - Classification standards tightened. PMID- 17842376 TI - New pressure on scientific exchanges. PMID- 17842377 TI - Stanford protests restrictions. PMID- 17842378 TI - Scientific collaboration in the middle East. PMID- 17842380 TI - Scientists start fund to fight antivivisectionists. PMID- 17842379 TI - Formaldehyde insulation ban overturned. PMID- 17842381 TI - A rescue mission for an agency in distress. PMID- 17842382 TI - Math meeting in poland questioned. PMID- 17842383 TI - Super phenix unscathed in rocket attack. PMID- 17842384 TI - Faculty v. OMB: One More Time. PMID- 17842386 TI - The hunter and the starcloud. PMID- 17842385 TI - The Dump That Wasn't There. PMID- 17842388 TI - 1981 AAAS Awards Presented in Washington. PMID- 17842387 TI - In the beginning. . PMID- 17842389 TI - 50-year members acknowledged. PMID- 17842391 TI - New publication. PMID- 17842390 TI - Pacific division plans june meeting. PMID- 17842393 TI - Puerto rican scientists and engineers form association. PMID- 17842392 TI - Reminder for section B. PMID- 17842394 TI - AAAS Socio-Psychological Prize. PMID- 17842395 TI - A somewhat forgotten physicist. PMID- 17842396 TI - Intelligence and some of its testers. PMID- 17842397 TI - The beetles. PMID- 17842398 TI - Insects and adaptations. PMID- 17842399 TI - Centennial contributions. PMID- 17842400 TI - Prescribed fire: effects on water quality and forest nutrient cycling. AB - Prescribed fire, a practice applied annually to about 10(6) hectares of forests in the southeastern United States, had limited effects on soils, nutrient cycling, and hydrologic systems of a coastal plain pine forest. Hydrologic fluxes of nitrogen, phosphorus, sulfur, and basic cations, from burned pine litter to ground and stream waters, are not likely to have appreciable impacts on water quality in the Atlantic and Gulf Coastal Plain. PMID- 17842401 TI - Salt diapirs bordering the continental margin of northern kenya and southern somalia. AB - The presence of newly discovered diapirs of presumed salt origin is documented for the continental margin of northeastern Kenya and southeastern Somalia. These structures are probably a manifestation of a significant thickness of Lower Jurassic evaporites deposited during the rift and early-drift stages of the separation of Madagascar from the African continent. PMID- 17842402 TI - Carbonyl sulfide and carbon disulfide from the eruptions of mount st. Helens. AB - Ash from the massive 18 May 1980 eruption of Mount St. Helens readily gave off large amounts of carbonyl sulfide and carbon disulfide gases at room temperature. These findings suggest that the sulfur that enhances the Junge sulfate layer in the stratosphere after volcanic eruptions could be carried directly to the upper atmosphere as carbonyl sulfide and carbon disulfide adsorbed on ash particles from major volcanic eruptions. PMID- 17842403 TI - Radiuin-226 and radon-222 in the coastal waters of west Florida: high concentrations and atmospheric degassing. AB - On the central portion of the west Florida continental shelf, radionuclide activities show unusually wide variations: radium-226 activities up to 350 disintegrations per minute per 100 liters, radon-222 activities up to 1300 disintegrations per minute per 100 liters, and deficiencies of radon-222 as low as -10 disintegrations per minute per 100 liters. Florida's phosphate-rich strata seerm to be the principal source of the radionuclides, with the transfer occurring directly from sediments or indirectly in streams, ground-water flow, and geothermal springs. Winter storm fronts may enhance radon degassing in the shelf waters. PMID- 17842404 TI - Thermal insulating capabilities of outdoor clothing materials. AB - A single heat transfer measurement technique was used to determine the thermal insulating capabilities of four materials used in outdoor clothing-goose down, wool, polyester, and polyolefin. It was found that all provide very similar degrees of insulation. PMID- 17842405 TI - Internal Hydrogen Bond Formation in a syn-Hydroxyepoxide. AB - The existence of an internal hydrogen bond in a compound representative of a syn diol epoxide (a possible intermediate in chemical carcinogenesis by certain polycyclic aromatic hydrocarbons) has been demonstrated by x-ray crystallographic and nuclear magnetic resonance studies. This internal hydrogen bond was found in 3,4-epoxy-2-methyl-1,2,3,4-tetrahydro-1-naphthol and was shown to persist in dioxane-water solutions containing up to 80 mole percent water. In this structure, the 1-hydroxy and 2-methyl groups are shown to occupy axial positions. In the anti diol epoxide, which has no internal hydrogen bond, analogous groups are equatorial. Crystals of the compound were unstable in the x-ray beam while the data were being collected (even at low temperatures), presumably as a result of decomposition. PMID- 17842406 TI - Fossil Genes: Scarce as Hen's Teeth? PMID- 17842407 TI - Fossil Genes: Scarce as Hen's Teeth? PMID- 17842408 TI - This week in science. PMID- 17842409 TI - World gas conference. PMID- 17842410 TI - Gaia modified. PMID- 17842411 TI - Translation of einstein papers. PMID- 17842412 TI - In reply: zombification. PMID- 17842414 TI - IOM Elects New Members. PMID- 17842413 TI - NIH to Review Disputed Data. PMID- 17842415 TI - Superfund program under fire. PMID- 17842416 TI - Mass retirement in the leadership of the soviet academy. PMID- 17842417 TI - Cosmos club drops ban on women. PMID- 17842418 TI - Einstein's Impossible Ring: Found. PMID- 17842419 TI - Relax, the sun is brightening again. PMID- 17842420 TI - A layer cake continent beneath the midwest. PMID- 17842421 TI - The Mantle's Structure--Having It Both Ways. PMID- 17842422 TI - How long does it take to build a mountain? PMID- 17842423 TI - The winner was .. PMID- 17842424 TI - The winter of '42. PMID- 17842425 TI - Softball science. PMID- 17842426 TI - Paleoceanography of coral reefs in the hawaiian-emperor chain. AB - The fossil record of shallow marine organisms in the Hawaiian Archipelago and Emperor seamount chain indicates that reef corals were absent during the first half of the Tertiary. Their appearance during the early Oligocene, 34 million years ago, is associated with several paleoceanographic events that appear to have combined to intensify gradually gyral surface currents in the north Pacific. This association suggests that corals were absent in the early Tertiary because of isolation of the Hawaiian Archipelago from the Indo-West Pacific (IWP), the center of reef coral abundance and diversity in the Pacific. Today, the number of species of reef corals in Hawaii is less than 10 percent of the number of species in the IWP. Since their initial colonization, reef corals have been present continuously in the Hawaiian Archipelago, although not without taxonomic change. Episodes of extinction and recolonization are the most likely cause of change in species composition. Recolonization from the IWP may also explain the low rate of endemism (about 20 percent) in the present-day coral fauna. PMID- 17842427 TI - Mixing in starts. AB - Analysis of the chemical and isotopic composition of stellar surfaces reveals the types of nuclear reactions that have occurred in the stellar interiors as well as the timing and depths from which material once deep in the star has reached the surface. Mass loss from the stellar surface and, in some cases, mass transfer from a companion enhance the opportunity to observe material that is the product of internal nuclear reactions. Detailed studies show substantial deficiencies in current models with the timing and depth of convective and other forms of mixing. PMID- 17842428 TI - Spectrum line intensity as a surrogate for solar irradiance variations. AB - Active Cavity Radiometer Irradiance Monitor (ACRIM) solar constant measurements from 1980 to 1986 are compared with ground-based, irradiance spectrophotometry of selected Fraunhofer lines. Both data sets were identically sampled and smoothed with an 85-day running mean, and the ACRIM total solar irradiance (S) values were corrected for sunspot blocking (S(c)). The strength of the mid-photospheric manganese 539.4-nanometer line tracks almost perfectly with ACRIM S(e), Other spectral features formed high in the photosphere and chromosphere also track well. These comparisons independently confirm the variability in the ACRIM S(e), signal, indicate that the source of irradiance is faculae, and indicate that ACRIM S(e), follows the 11-year activity cycle. PMID- 17842429 TI - Deuterium on Mars: The Abundance of HDO and the Value of D/H. AB - Deuterium on Mars has been detected by the resolution of several Doppler-shifted lines ofHDO near 3.7 micrometers in the planet's spectrum. The ratio of deuterium to hydrogen is (9 +/- 4) x 10(-4); the abundance of H(2)0 was derived from lines near 1.1 micrometers. This ratio is enriched on Mars over the teiluric value by a factor of6 +/- 3. The enrichment implies that hydrogen escaped more rapidly from Mars in the past than it does now, consistent with a dense and warm ancient atmosphere on the planet. PMID- 17842430 TI - Anomalous upstream retroflection in the agulhas current. AB - The Agulhas current, the major western boundary current of the Southern Hemisphere, plays a crucial role in the water mass balance ofthe world oceans by controlling the transfer of thernocline water from the Indian to the Atlantic ocean systems. The main mechanism for such transfer is through the shedding of large rings of warm water at the Agulhas retroflection south ofAfrica. On the basis ofsatellite imagery and drifter tracks, anomalous reversals ofthe current are observed to occur far upstream of its characteristic retroflection location. The observations agree with results of an inertial jet model ofthe current. These anomalous reversals probably cause abrupt and major changes in the fluxes south ofAfrica and thus in the rate of ring shedding. This unusual flow bimodality in a major component of the global ocean heat transport system could have important climatic implications. PMID- 17842431 TI - Coevolution of sender and receiver: effect on local mate preferecnce in cricket frogs. AB - Mate recognition in frogs requires congruence of call characters, such as dominant frequency, and properties ofthe auditory system, such as frequency sensitivity of inner ear organs. Two neighboring populations of cricket frogs (Acri crepitans) exhibit statistically significant differences in the dominant frequency of the advertisement call and the frequency to which the basilar papilla of the inner ear is most sensitive. Call frequency and frequency sensitivity are matched within but differ between populations. These characters usually are negatively correlated with body size, and thus their congruence and coevolution often is explained by pleiotropic effects of size. However, within this species call frequency and frequency sensitivity ofthe basilar papilla evolved independent of body size, yielding local mate preferences that could contribute to genetic differentiation among neighboring populations. PMID- 17842432 TI - A new speciment of archaeopteryx. AB - A new specimen of the primordial bird Archaeopteryx is reported from the Upper Jurassic Solnhofen Limestone of Bavaria. This "Solnhofen specimen" is the largest of now six skeletal specimens and shows dose similarities with the London specimen. It is therefore assigned to Archaeopteryx lithographica Meyer. Clear impressions of the feather shafts of the left wing are preserved. PMID- 17842433 TI - In Reply: Amplification c-erbB-2 and Aggressive Human Breast Tumors? PMID- 17842434 TI - Aaas annual meeting. PMID- 17842436 TI - Neural Darwinism. The Theory of Neuronal Group Selection. Gerald M. Edelman. Basic Books, New York, 1987. xxii, 371 pp., illus. $29.95. PMID- 17842438 TI - Products & materials. PMID- 17842439 TI - SCIENCE NEWS. PMID- 17842441 TI - ON THE LOCOMOTION OF SNAKES. PMID- 17842442 TI - OBITUARY. PMID- 17842440 TI - ON THE RELATIONS OF STELLAR ELECTRICITY AND MAGNETISM TO THE PHENOMENA OF THE SUN'S ATMOSPHERE. PMID- 17842444 TI - NUTRITIONAL REQUIREMENTS OF TROUT. PMID- 17842445 TI - PHOTOPERIODISM AND CHRYSANTHEMUM PRODUCTION. PMID- 17842443 TI - THE ANCESTRY OF ECHINI. PMID- 17842446 TI - PARTHENOCARPY AND SEEDLESSNESS IN VITIS VINIFERA. PMID- 17842447 TI - IMPROVEMENTS IN BIOLOGICAL LABORATORY APPARATUS. PMID- 17842448 TI - ON VOLUMETERS FOR SOLID BODIES. PMID- 17842449 TI - THE ATLANTIC CITY MEETING. PMID- 17842450 TI - AN IMPROVED METHOD FOR THE STUDY OF DIFFUSIBLE BACTERIAL PRODUCTS IN VIVO. PMID- 17842451 TI - THE PRESS SERVICE. PMID- 17842452 TI - THE SCIENCE EXHIBITION. PMID- 17842453 TI - CARBON DIOXIDE AS A FACTOR AFFECTING LAG IN BACTERIAL GROWTH. PMID- 17842454 TI - SOME SOCIAL AND ECONOMIC PARADOXES. PMID- 17842455 TI - SCHOOL OF MECHANIC ARTS AT THE ALABAMA POLYTECHNIC INSTITUTE. PMID- 17842456 TI - ELECTRICAL SCIENCE. PMID- 17842457 TI - MENTAL SCIENCE. PMID- 17842458 TI - HEALTH MATTERS. PMID- 17842459 TI - Volapuk : Is it Difficult? PMID- 17842461 TI - ABBOTT LAWRENCE ROTCH. PMID- 17842460 TI - UNIVERSITY CONTROL. PMID- 17842462 TI - THE TRANSCONTINENTAL EXCURSION OF THE AMERICAN GEOGRAPHICAL SOCIETY. PMID- 17842463 TI - A PROTEST AGAINST CHANGING THE INTERNATIONAL CODE OF ZOOLOGICAL NOMENCLATURE. PMID- 17842464 TI - CRYSTALLOGRAPHIC TABLES. PMID- 17842465 TI - "GENES" OR "GENS"? PMID- 17842466 TI - CHANGES OF BODILY FORM IN DESCENDANTS OF IMMIGRANTS. PMID- 17842467 TI - BOTANICAL NOTES. PMID- 17842468 TI - THE INEFFICIENCY OF WIRES AS A MEANS OF CURING DEFECTIVE ACOUSTICS OF AUDITORIUMS. PMID- 17842469 TI - COLOR VARIATIONS OF THE HOUSE MOUSE IN CALIFORNIA. PMID- 17842470 TI - CERTAIN ASPECTS OF THE CHEMISTRY OF INFECTIOUS DISEASES. PMID- 17842471 TI - THE IMPORTANCE OF MICROORGANISMS IN VITAMIN RESEARCH. PMID- 17842472 TI - HERBERT FREUNDLICH 1880-1941. PMID- 17842473 TI - THE ELLEN H. RICHARDS INSTITUTE. PMID- 17842475 TI - ARMY SERVICE OF MEDICAL STUDENTS AND INTERNS. PMID- 17842474 TI - THE INSTITUTE OF GEO-BIOLOGY IN PEKING. PMID- 17842476 TI - EXCHANGE OF ASTRONOMICAL PAPERS WITH FOREIGN COUNTRIES. PMID- 17842477 TI - THE AMERICAN PHILOSOPHICAL SOCIETY. PMID- 17842478 TI - THE RATE OF PERFORMANCE OF OSMOTIC WORK ON THE CHLORIDE ION DURING ACTIVE INTESTINAL ABSORPTION. PMID- 17842480 TI - RESEARCH IN TROPICAL AMERICA. PMID- 17842479 TI - THE MOUSE ANTIALOPECIA FACTOR. PMID- 17842481 TI - NEED FOR THE PRESERVATION OF NATURAL AREAS EXEMPLIFYING VEGETATION TYPES. PMID- 17842482 TI - ACETYL AND PHENYLUREIDO DERIVATIVES OF TOBACCO MOSAIC VIRUS. PMID- 17842483 TI - LEUCOCYTE LEVEL AND LONGEVITY IN RATS. PMID- 17842484 TI - ON THE SIZE OF THE LITTER AND THE GESTATION PERIOD OF PROCAVIA CAPENSIS. PMID- 17842485 TI - AN IMPROVED CELL FOR OPTICAL DIFFUSION MEASUREMENTS ON SOLUTIONS. PMID- 17842486 TI - A SIMPLE, THIN AQUARIUM. PMID- 17842487 TI - PROBLEMS AND POSSIBILITIES OF SYSTEMATIC BOTANY. PMID- 17842489 TI - SECTION C (CHEMISTRY) OF THE AMERICAN ASSOCIATION. PMID- 17842488 TI - THE CHANGE OF FRONT IN EDUCATION. PMID- 17842490 TI - MEMBERSHIP OF THE AMERICAN ASSOCIATION. PMID- 17842491 TI - WEATHER CONTROL. PMID- 17842492 TI - REVIEW OF TWO RECENT PAPERS ON BAHAMAN CORALS. PMID- 17842493 TI - RECENT ZOO-PALEONTOLOGY. PMID- 17842494 TI - TWO UNKNOWN WORKS OF RAFINESQUE. PMID- 17842495 TI - REPORTS OF FOREIGN MUSEUMS. PMID- 17842496 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17842498 TI - TIME-PERIODS OF THE MAYAS. PMID- 17842497 TI - THE BOTURINI-AUBIN-GOUPIL COLLECTION OF MEXICANA. PMID- 17842499 TI - NOTES ON THE FORMATION OF THE IRON ORES. PMID- 17842500 TI - THE PERMIAN IN PRINCE EDWARD ISLAND. PMID- 17842501 TI - AN OLD VOLCANIC ERUPTION IN IOWA. PMID- 17842502 TI - CURRENT NOTES ON ANTHROPOLOGY.-XXIV. PMID- 17842503 TI - NOTES ON THE WING-COLOR OF NORTH AMERICAN LOCUSTS BELONGING TO THE SUB-FAMILY CEDIPODINAe AND ITS SEEMING RELATION TO CLIMATIC CONDITIONS. PMID- 17842504 TI - A Reply to Professor Hathaway. PMID- 17842505 TI - A Question of Evidence. PMID- 17842506 TI - The Speech of Children. PMID- 17842507 TI - Hardy Towhee Buntings. PMID- 17842508 TI - Aerial Bubbles. PMID- 17842509 TI - The Neanderthal Skull. PMID- 17842510 TI - Solidungulate Pigs. PMID- 17842511 TI - THE LEWIS AND CLARK EXPEDITION. PMID- 17842512 TI - SPIRAL NEBULAE. PMID- 17842513 TI - MOUNTAIN CHAIN FORMATION. PMID- 17842514 TI - THE POLLUTION OF WELLS. PMID- 17842515 TI - OXYGEN AND THE GROWTH OF BACTERIA. PMID- 17842516 TI - PURE ALUMINUM. PMID- 17842517 TI - TROPICAL CLIMATES. PMID- 17842518 TI - THE BISON IN CANADA. PMID- 17842519 TI - ARTISTRY IN "ANNIE LAURIE" MEASURED BY SCIENCE. PMID- 17842520 TI - THE GROWING OPPORTUNITIES FOR MEDICAL RESEARCH. PMID- 17842521 TI - THE TREND OF THOUGHT IN PHYSICS. II. AB - In its fundamental aspects, practically the whole of modern physics is concerned with the discussion of the relations which exist between the motions of two sets of points in such a way as to establish a sort of one-one correspondence between the things which we do, and the behavior of one set of points on the one hand, and the things which we observe and the behavior of the other set of points on the other hand. We send a beam of electrons through an X-ray tube, and certain dark lines appear on photographic plates elsewhere, or electrons are emitted with certain velocities which we measure indirectly. As regards the electrons which are emitted into our apparatus, we can almost say that we observe them directly. As regards the blackening of the photographic plate, we are content if we can account for certain electronic emissions or motions to which we can attribute it. We do not, however, try to establish a direct relation between the original beam of electrons and the photographic plate or photoelectric cell, because we find that certain other apparatus was necessary for the experiment, a calcite grating and X-ray target, and so forth. These pieces of apparatus are replaced in the mind's eye by other sets of points grouped into atoms and molecules, in a manner characteristic of the substances in such a way that we may hope to be able to establish a relation between the first set of points, those in the target, those in the calcite and those in the final photographic plate or photoelectric cell. The whole problem is to discover how the points must be assigned and what function their mutual motions are of each other in order that the correlation may be satisfactorily made. PMID- 17842522 TI - THE WHITE INDIANS OF THE SAN BLAS AND DARIEN. PMID- 17842523 TI - THE JAMES SIMPSON-ROOSEVELT EXPEDITION OF THE FIELD MUSEUM OF NATURAL HISTORY. PMID- 17842524 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17842525 TI - THE UNDERTOW. PMID- 17842526 TI - SERIES IN THE ARC SPECTRUM OF NITROGEN. PMID- 17842527 TI - THE STEM OF MAGNOLIA AS A LABORATORY TYPE. PMID- 17842529 TI - THE NORWEGIAN IDENTITY BOOK. PMID- 17842528 TI - ORIGIN OF THE LOESS OF THE PALOUSE REGION, WASHINGTON. PMID- 17842530 TI - A HIGHLY SENSITIVE PHYSICAL METHOD FOR DETECTING PROTEINS IN A SOLUTION. PMID- 17842531 TI - GEOLOGIC ANTIQUITY OF MAN IN AMERICA. PMID- 17842532 TI - WILLIAM WEBBER FORD 1871-1941. PMID- 17842533 TI - SYMPOSIUM ON THE RESPIRATORY ENZYMES AND THE BIOLOGICAL ACTION OF THE VITAMINS. PMID- 17842534 TI - THE HARVARD FOREST. PMID- 17842535 TI - THE AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17842537 TI - SUMMER MEETINGS OF THE AMERICAN MATHEMATICAL SOCIETY. PMID- 17842536 TI - PRESENTATION OF THE WILLARD GIBBS MEDAL. PMID- 17842538 TI - HONORARY DEGREES TO BE CONFERRED AT THE FIFTIETH ANNIVERSARY OF THE UNIVERSITY OF CHICAGO. PMID- 17842540 TI - THE ACTIVE PRINCIPLE OF MARIHUANA. PMID- 17842539 TI - IS EVOLUTION INSCRUTABLE? PMID- 17842541 TI - KARL FRIEDRICH GAUSS AND HIS FAMILY RELATIVES. PMID- 17842543 TI - THE BIOTIN CONTENT OF TUMORS AND OTHER TISSUES. PMID- 17842542 TI - DESIGINATION OF LOCATIONS ON MAPS AND PHOTOGRAPHS. PMID- 17842544 TI - NORTH CAROLINA ACADEMY OF SCIENCE. PMID- 17842545 TI - THE PRESERVATION BY FREEZING AND DRYING IN VACUO OF THE MILK-INFLUENCE FOR THE DEVELOPMENT OF BREAST CANCER IN MICE. AB - The development of spontaneous breast cancer in mice following the feeding of lyophilized tissue prepared from breast tumors suggests that the active influence usually transferred in the milk by nursing may be a virus. PMID- 17842547 TI - REPORT ON THE NAVAL OBSERVATORY. PMID- 17842546 TI - A PROBABLE AGENT FOR THE TRANSMISSION OF FOWL PARALYSIS. PMID- 17842548 TI - REPORT OF THE BOARD OF VISITORS TO THE UNITED STATES NAVAL OBSERVATORY, OCTOBER 2, 1899. Washington, D. C., ctober 2, 1899. PMID- 17842549 TI - ADDRESS OF THE PRESIDENT OF THE GEOGRAPHICAL SECTION OF THE BRITISH ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. I. PMID- 17842550 TI - THE EARLY PRESIDENTS OF THE AMERICAN ASSOCIATION. IV. PMID- 17842551 TI - THE SENSE OF HEARING IN ANTS. PMID- 17842552 TI - ARE THE TREES ADVANCING OR RETREATING UPON THE NEBRASKA PLAINS? PMID- 17842553 TI - PRELIMINARY NOTE ON NEW METEORITES FROM ALLEGAN, MICHIGAN AND MART, TEXAS. PMID- 17842556 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17842555 TI - THE NEED FOR A CLASSIFICATION OF PREHISTORIC IMPLEMENTS. PMID- 17842554 TI - PERMANENT PREPARATIONS IN HERMETICALLY SEALED TUBES. PMID- 17842558 TI - REPORT OF THE PRESIDENT OF COLUMBIA UNIVERSITY. PMID- 17842557 TI - INTERNATIONAL METEOROLOGICAL COMMITTEE. PMID- 17842559 TI - PRESIDENT'S ADDRESS AT THE INTERNATIONAL MEDICAL CONGRESS. PMID- 17842561 TI - DOCTORATES CONFERRED BY AMERICAN UNIVERSITIES. PMID- 17842560 TI - CEREAL CROPPING: SANITATION, A NEW BASIS FOR CROP ROTATION, MANURING, TILLAGE AND SEED SELECTION. PMID- 17842562 TI - "CARBATES". PMID- 17842563 TI - A SECOND CAPTURE OF THE WHALE SHARK, RHINEODON TYPUS, IN FLORIDA WATERS. PMID- 17842564 TI - FROST IN CALIFORNIA. PMID- 17842565 TI - THE RUTHERFORD ATOM. PMID- 17842566 TI - NOTES ON ENTOMOLOGY. PMID- 17842567 TI - PRELIMINARY NOTE ON BIRDS AS CARRIERS OF THE CHESTNUT BLIGHT FUNGUS. PMID- 17842568 TI - THE RELATION BETWEEN ABNORMAL PERMEABILITY AND ABNORMAL DEVELOPMENT OF FUNDULUS EGGS. PMID- 17842570 TI - A PLEA FOR THE STUDY OF THE HISTORY OF MEDICINE AND NATURAL SCIENCES. PMID- 17842569 TI - SOME PHYSIOLOGICAL VARIATIONS OF PLANTS, AND THEIR GENERAL SIGNIFICANCE. PMID- 17842571 TI - A PROTEST ON BEHALF OF THE SYSTEMATIC ZOOLOGIST AND THE BIBLIOGRAPHER. PMID- 17842573 TI - UPLIFT INCREASES RAINFALL, DENUDATION DIMINISHES IT. PMID- 17842572 TI - SCIENCE AND POETRY--A PROTEST. PMID- 17842574 TI - CONCERNING LEFT-HANDED ABORIGINES. PMID- 17842575 TI - THE DEVELOPMENT OF UNFERTILIZED FROG EGGS INJECTED WITH BLOOD. PMID- 17842576 TI - TRANSMISSION INHERITANCE DISTINCT FROM EXPRESSION INHERITANCE. PMID- 17842577 TI - A NEW METHOD BY WHICH SPONGES MAY BE ARTIFICIALLY REARED. PMID- 17842578 TI - SCIENCE IN MUSIC. PMID- 17842579 TI - THE TASKS BEFORE US. PMID- 17842581 TI - THE INTER-AMERICAN TREATY ON NATURE PROTECTION. PMID- 17842580 TI - HERBERT FOX. PMID- 17842582 TI - THE WILLIAM LOWELL PUTNAM MATHEMATICAL COMPETITION. PMID- 17842584 TI - A CHINESE SCIENTIFIC SOCIETY ON WEST COAST. PMID- 17842583 TI - THE AMERICAN SOCIETY OF MAMMALOGISTS. PMID- 17842585 TI - GRANTS OF THE NUTRITION FOUNDATION. PMID- 17842586 TI - THE AMERICAN ASSOCIATION OF PATHOLOGISTS AND BACTERIOLOGISTS. PMID- 17842587 TI - THE SACRAL SPOT IN BENGAL. PMID- 17842589 TI - CREDIDMUS JOVEM REGNARE. PMID- 17842588 TI - CARBONATE-APATITE AND HYDROXYLAPATITE IN URINARY CALCULI. PMID- 17842590 TI - HUMBOLDT CURRENT IN 1941. PMID- 17842591 TI - A SIMPLE METHOD OF CONTROLLING TERMITES. PMID- 17842592 TI - SCIENCE AND WAR. PMID- 17842593 TI - FELLOWSHIPS IN SCIENCE AWARDED BY THE GUGGENHEIM FOUNDATION. PMID- 17842594 TI - A NEW PROCEDURE FOR STAINING VAGINAL SMEARS. PMID- 17842595 TI - FERRITIN AND APOFERRITIN. PMID- 17842596 TI - THE PRODUCTION OF ANTIBODIES IN VITRO. PMID- 17842597 TI - THE USE OF THE COMPLEMENT FIXATION TEST IN ROCKY MOUNTAIN SPOTTED FEVER. PMID- 17842598 TI - Science: the broader context. PMID- 17842599 TI - Science: the broader context. PMID- 17842601 TI - Science: the broader context. PMID- 17842600 TI - Science: the broader context. PMID- 17842602 TI - Response: CD2: An Exception to the Immunologlobulin Superfamily Concept? PMID- 17842603 TI - The Astronomical League A New Associated Society of the American Association for the Advancement of Science. PMID- 17842604 TI - Meetings & Conferences. PMID- 17842606 TI - Bienvenido Maria Gonzalez: 1893-1953. PMID- 17842605 TI - Scientists in Communist China. PMID- 17842608 TI - Nuclear Emulsions for Electron Microscopy. PMID- 17842607 TI - Scientists' Definition of Public Relations Not Scientific. PMID- 17842609 TI - The Fungistatic Action of Squalene on Certain Dermatophytes in Vitro. PMID- 17842611 TI - Miscellaneous Publications. PMID- 17842610 TI - Thermal Precipitation Analyzed. PMID- 17842612 TI - This week in science. PMID- 17842614 TI - Erratum. AB - In R. Jeffrey Smith's article "Beggs takes a leave of absence at NASA" (News and Comment, 20 Dec., p. 1363), NASA acting administrator William R. Graham was incorrectly identified as "Thomas Graham." PMID- 17842613 TI - Planet Earth. PMID- 17842615 TI - Gastronomic variety. PMID- 17842616 TI - SSC Design. PMID- 17842618 TI - The national science board. PMID- 17842617 TI - Genetic engineering. PMID- 17842619 TI - NASA and Military Press for a Spaceplane: The aerospace plane, a possible alternative to the shuttle, is to be designed with military goals in mind more than commercial travel. PMID- 17842620 TI - A Risk Reduction Center Gains U.S. Support: A series of shrewd maneuvers by two congressmen led to an agreement at the summit to start bilateral talks on risk reduction centers. PMID- 17842621 TI - Soviets Launch Computer Literacy Drive: High school students are now being taught the basics without machines; a serviceable domestic PC is yet to be produced. PMID- 17842623 TI - High selenium levels confirmed in six States. PMID- 17842622 TI - NRC Finds Crisis in Remote Sensing. PMID- 17842624 TI - When Stones Can Be Deceptive: A young archeologist has been making and using hundreds of stone tools in order to learn what our ancestors did with them; some unexpected results emerged. PMID- 17842625 TI - Dexterous early hominids. PMID- 17842626 TI - A search for another san andreas. PMID- 17842627 TI - Parkfield earthquake looks to be on schedule. PMID- 17842629 TI - Long Valley is Quiet but Still Bulging. PMID- 17842628 TI - How to stir up a deep-sea storm. PMID- 17842630 TI - Background and mass extinctions: the alternation of macroevolutionary regimes. AB - Comparison of evolutionary patterns among Late Cretaceous marine bivalves and gastropods during times of normal, background levels of extinction and during the end-Cretaceous mass extinction indicates that mass extinctions are neither an intensification of background patterns nor an entirely random culling of the biota. During background times, traits such as planktotrophic larval development, broad geographic range of constituent species, and high species richness enhanced survivorship of species and genera. In contrast, during the, end-Cretaceous and other mass extinctions these factors were ineffectual, but broad geographic deployment of an entire lineage, regardless of the ranges of its constituent species, enhanced survivorship. Large-scale evolutionary patterns are evidently shaped by the alternation of these two macroevolutionary regimes, with rare but important mass extinctions driving shifts in the composition of the biota that have little relation to success during the background regime. Lineages or adaptations can be lost during mass extinctions for reasons unrelated to their survival values for organisms or species during background times, and long-term success would require the chance occurrence within a single lineage of sets of traits conducive to survivorship under both regimes. PMID- 17842631 TI - Atmospheric deposition and canopy interactions of major ions in a forest. AB - Airborne particles and vapors contributed significantly to the nutrient requirements and the pollutant load of a mixed hardwood forest in the eastern United States. Dry deposition was an important mechanism of atmospheric input to the foliar canopy, occurring primarily by vapor uptake for sulfur, nitrogen, and free acidity and by particle deposition for calcium and potassium. The canopy retained 50 to 70 percent of the deposited free acidity and nitrogen, but released calcium and potassium. Atmospheric deposition supplied 40 and 100 percent of the nitrogen and sulfur requirements, respectively, for the annual woody increment. This contribution was underestimated significantly by standard bulk deposition collectors. PMID- 17842632 TI - Ethnological Displays: All the World's a Fair. PMID- 17842633 TI - The contours of a debate: the intelligence men. PMID- 17842634 TI - Chinese micropaleontology: marine micropaleontology of china and acta micropalaeontologica sinica. PMID- 17842635 TI - Glirology: Evolutionary Relationships among Rodents. PMID- 17842636 TI - The study of polymers: polymers. PMID- 17842638 TI - PROFESSOR THOMAS HARRISON MONTGOMERY, JR. PMID- 17842637 TI - Products & materials. PMID- 17842639 TI - FORECAST OF THE BIRMINGHAM MEETING OF THE BBITISH ASSOCIATION. PMID- 17842641 TI - THE FOURTH INTERNATIONAL CONGRESS OF SCHOOL HYGIENE. PMID- 17842640 TI - THE PRINCIPLE OF MENTAL TESTS. PMID- 17842642 TI - NOTE ON THE ORIENTATION OF BOMBILIUS TO LIGHT. PMID- 17842643 TI - THE NAME OF THE SHEEP MEASLE TAPEWORM. PMID- 17842644 TI - BOTANICAL NOTES. PMID- 17842645 TI - THE APPLICABILITY OF THE PHOTOCHEMICAL ENERGY-LAW TO LIGHT REACTIONS IN ANIMALS. PMID- 17842647 TI - MEDAL PRESENTATIONS: REMARKS BY THE PRESIDENT. PMID- 17842646 TI - THE IOWA ACADEMY OF SCIENCE. PMID- 17842648 TI - PRESENTATION OF THE AGASSIZ MEDAL FOR THE YEAR 1942, WITH ACCOMPANYING HONORARIUM OF $300, TO COLUMBUS O'DONNELL ISELIN II. PMID- 17842649 TI - PRESENTATION OF THE HENRY DRAPER MEDAL FOR 1942 TO IRA SPRAGUE BOWEN. PMID- 17842650 TI - PRESENTATION OF THE DANIEL GIRAUD ELLIOT MEDAL FOR 1935 WITH ACCOMPANYING HONORARIUM OF $200, TO EDWIN H. COLBERT. PMID- 17842651 TI - PRESENTATION OF THE JOHN J. CARTY MEDAL AND AWARD (MONETARY AWARD $4,000) TO EDWIN GRANT CONKLIN. PMID- 17842652 TI - PRESENTATION OF THE DANIEL GIRAUD ELLIOT MEDAL FOR 1936, WITH ACCOMPANYING HONORARIUM OF $200, TO ROBERT CUSHMAN MURPHY. PMID- 17842653 TI - MARY JANE RATHBUN. PMID- 17842654 TI - MUSEUM ATTENDANCE AND THE WAR. PMID- 17842656 TI - THE BROOKLYN BOTANIC GARDEN. PMID- 17842655 TI - THE RADCLIFFE CHAPTER OF THE SOCIETY OF THE SIGMA XI. PMID- 17842657 TI - THE AMERICAN COORDINATING COMMITTEE ON CORROSION. PMID- 17842658 TI - THE AMERICAN CHEMICAL SOCIETY AND THE KILGORE BILL. PMID- 17842659 TI - POSITIONS WITH THE NAVY. PMID- 17842660 TI - THE FORMATION OF MOSS PEAT BENEATH TRANSLUCENT PEBBLES IN SEMI-ARID REGIONS OF THE GREAT PLAINS. PMID- 17842661 TI - THE KILGORE SENATE BILL. PMID- 17842663 TI - SCIENCE AND THE CENSOR. PMID- 17842662 TI - BIOLOGICAL SPECIFICITY OF FOLIC ACID. PMID- 17842664 TI - WARTIME ACTIVITIES OF MELLON INSTITUTE, 1942-43. PMID- 17842665 TI - SYNTHETIC BIOTIN. PMID- 17842667 TI - NEW METHOD OF DETERMINATION OF THE CHOLINE-ESTERASE ACTIVITY. PMID- 17842666 TI - PERSISTENCE OF YELLOW FEVER VIRUS IN THE BRAINS OF MONKEYS IMMUNIZED BY CEREBRAL INOCULATION. PMID- 17842668 TI - CHEMICAL STUDIES ON CRYSTALLINE BARIUM ACID HEPARINATE. PMID- 17842669 TI - This week in science. PMID- 17842671 TI - Africanized honeybees. PMID- 17842670 TI - Computer science funding. PMID- 17842672 TI - Arms control and intricacy. PMID- 17842673 TI - Strained-layer epitaxy of germanium-silicon alloys. AB - Despite the dominant position of silicon in semiconductor electronics, its use is ultimately limited by its incompatibility with other semiconducting materials. Strained-layer epitaxy overcomes problems of crystallographic compatibility and produces high-quality heterostructures of germanium-silicon layers on silicon. This opens the door to a range of electronic and photonic devices that are based on bandstructure physics. PMID- 17842674 TI - Life at high temperatures. AB - Water environments with temperatures up to and above boiling are commonly found in association with geothermal activity. At temperatures above 60 degrees C, only bacteria are found. Bacteria with temperature optima over the range 65 degrees to 105 degrees C have been obtained in pure culture and are the object of many research projects. The upper temperature limit for life in liquid water has not yet been defined, but is likely to be somewhere between 110 degrees and 200 degrees C, since amino acids and nucleotides are destroyed at temperatures over 200 degrees C. Because bacteria capable of growth at high temperatures are found in many phylogenetic groups, it is likely that the ability to grow at high temperature had a polyphyletic origin. The macromolecules of these organisms are inherently more stable to heat than those of conventional organisms, but only small changes in sequence can lead to increases in thermostability. Because of their unique properties, thermophilic organisms and their enzymes have many potential biotechnological uses, and extensive research on industrial applications is under way. PMID- 17842675 TI - What makes a good computer device? AB - Numerous development projects aimed at replacing the silicon technology that dominates computer logic with a faster alternative have been conducted throughout the past 25 years. None has succeeded. The alternatives are usually based on a device that switches very rapidly, and they neglect many other requirements of computer logic. In this article the essential physical factors that account for the success of transistors in digital applications are identified, as are the factors that are absent in proposed alternative devices. PMID- 17842677 TI - DOE, States Reheat Nuclear Waste Debate: States fear the department is compromising the process for selecting a permanent disposal site by pushing to meet Congress's 1998 deadline. PMID- 17842676 TI - Production of 2-Keto-L-Gulonate, an Intermediate in L-Ascorbate Synthesis, by a Genetically Modified Erwinia herbicola. AB - A new metabolic pathway has been created in the microorganism Erwinia herbicola that gives it the ability to produce 2-keto-L-gulonic acid, an important intermediate in the synthesis of L-ascorbic acid. Initially, a Corynebacterium enzyme that could stereoselectively reduce 2,5-diketo-D-gluconic acid to 2-keto-L gulonic acid was identified and purified. DNA probes based on amino acid sequence information from 2,5-diketo-D-gluconic acid reductase were then used to isolate the gene for this enzyme from a Corynebacterium genomic library. The 2,5-diketo-D gluconic acid reductase coding region was fused to the Escherichia coli trp promoter and a synthetic ribosome binding site and was then introduced into E. herbicola on a multicopy plasmid. Erwinia herbicola naturally produces 2,5-diketo D-gluconic acid via glucose oxidation, and when recombinant cells expressing the plasmid-encoded reductase were grown in the presence of glucose, 2-keto-L-gulonic acid was made and released into the culture medium. The data demonstrate the feasibility of creating novel in vivo routes for the synthesis of important specialty chemicals by combining useful metabolic traits from diverse sources in a single organism. PMID- 17842678 TI - Star wars boycott gains strength. PMID- 17842679 TI - White house issues secrecy guideline. PMID- 17842680 TI - Comings and goings. PMID- 17842681 TI - China to permit inspection of some nuclear facilities. PMID- 17842682 TI - EPA moves tentatively on two air pollutants. PMID- 17842683 TI - Britain's Oil Bubble About to Deflate: The result will be less government revenue but greater funding for research and new technologies, and more jobs. PMID- 17842684 TI - How Rhizobia and Legumes Get It Together: Formation of nitrogen-fixing nodules on legume roots requires an intricate interplay between the plant and the nodulating rhizobial bacterium. PMID- 17842686 TI - 1986 AAAS ANNUAL MEETING Philadelphia, 25-30 May. PMID- 17842685 TI - The Core of the Milky Way: Our galaxy appears to be a miniature quasar; all the evidence now points to an enormous black hole at the center. PMID- 17842687 TI - Atmospheric Evolution: The Carbon Cycle and Atmospheric CO2. PMID- 17842688 TI - Cosmic distances: the cosmological distance ladder. PMID- 17842689 TI - The adoption of anesthesia: a calculus of suffering. PMID- 17842690 TI - Pierre duhem: uneasy genius. PMID- 17842691 TI - Primate evolution and human origins. PMID- 17842692 TI - Some other books of interest: possums and gliders. PMID- 17842693 TI - Cretaceous extinctions: evidence for wildfires and search for meteoritic material. AB - Clay samples from three Cretaceous-Tertiary boundary sites contain 0.36 to 0.58 percent graphitic carbon, mainly as fluffy aggregates of 0.1 to 0.5 micrometers apparently a worldwide layer of soot. It may have been produced by wildfires triggered by a giant meteorite. This carbon, corresponding to a global abundance of 0.021 +/- 0.006 gram per square centimeter, could have greatly enhanced the darkening and cooling of the earth by rock dust, which has been suggested as a cause of the extinctions. The surprisingly large amount of soot (10 percent of the present biomass of the earth) implies either that much of the earth's vegetation burned down or that substantial amounts of fossil fuels were ignited also. The particle-size distribution of the soot is similar to that assumed for the smoke cloud of "nuclear winter," but the global distribution is more uniform and the amounts are much greater, suggesting that soot production by large wildfires is about 10 times more efficient that has been assumed for a nuclear winter. Thus cooling would be more pervasive and lasting. No trace of meteoritic noble gases and no meteoritic spinel were found in these carbon fractions. Accordingly, limits can be set on the mass fraction of the meteorite that escaped degassing (30%) found in cherts from arid, alkaline environments may resurrect length-slow silica as an indicator of evaporitic regimes, and the absence of moganite in weathered and hydrothermally altered silica samples may be a useful measure of fluid-rock interaction. PMID- 17842896 TI - Shocked quartz at the triassic-jurassic boundary in Italy. AB - Quartz grains that appear to have been shock-metamorphosed occur within three closely spaced shale beds from the uppermost Triassic ("Rhaetian") Calcare a Rhaetavicula in the Northern Apennines of Italy. The upper shale coincides with the abrupt termination of the distinctive, uppermost Triassic Rhaetavicula fauna and is overlain by the Hettangian (Lower Jurassic) Calcare Massiccio; no extinctions appear to be associated with the two lower layers, which occur 1.2 and 2.4 meters below the boundary shale. Approximately 5 to 10% of the quartz grains within these layers exhibit one or more sets of planar deformational features whose orientations cluster around the rational crystallographic planes (basal, omega, and pi) most commonly observed in shocked quartz. Textural and stratigraphic observations support an interpretation of at least three closely spaced impacts at the end of the Triassic. PMID- 17842897 TI - Optically transparent, electrically conductive composite medium. AB - The development of an optically transparent yet electrically conductive material made with a composite structure having preferentially arranged conductive paths is described. The medium contains many vertically aligned but laterally isolated chains of ferromagnetic spheres dispersed in a sheet of transparent polymer. The sheet material transmits more than 90 percent of the incident light and is highly conductive only in the thickness direction. When suitably modified, the material exhibits on-off electrical switchability at a certain threshold pressure. These characteristics confer potential usefulness for visual communication devices such as write pads or touch-sensitive screens. PMID- 17842898 TI - To witness and heal: what science can do to respond to human rights abuse. PMID- 17842899 TI - AAAS Award Winners. PMID- 17842900 TI - 1992 AAAS Dues. PMID- 17842901 TI - AAAS Fellow Nominations. PMID- 17842902 TI - Congress boosts funding for science. PMID- 17842903 TI - The right to self-harm. PMID- 17842904 TI - Vignettes: Earth health. PMID- 17842905 TI - German imports. PMID- 17842907 TI - Products & materials. PMID- 17842906 TI - Some other books of interest. PMID- 17842908 TI - SCIENCE NEWS. PMID- 17842909 TI - OPERATIVE VERSUS ABSTRACT PHILOSOPHY IN PHYSICS. PMID- 17842910 TI - JULIUS ROBERT MAYER AND THE BLOOD'S CIRCULATION RATE. PMID- 17842911 TI - JOHN J. FLATHER. PMID- 17842912 TI - A PROGRAM FOR BIOLOGISTS. PMID- 17842913 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17842914 TI - THE DE REVOLUTIONIBUS ORBIUM COELESTIUM. PMID- 17842915 TI - MILLING AND BAKING QUALITIES OF OLD WHEAT. PMID- 17842916 TI - A PLANT NEW TO THE UNITED STATES. PMID- 17842917 TI - THE USE OF ARCS AND OTHER FLUCTUATING SOURCES IN PHOTO-ELECTRIC PHOTOMETRY. PMID- 17842918 TI - QUARTET AND DOUBLET TERMS IN THE COPPER SPECTRUM. PMID- 17842919 TI - BLOOD STUDIES IN GENERAL ANESTHESIA. PMID- 17842920 TI - Stochastic Models. PMID- 17842921 TI - The Term "Cosmoparticle". PMID- 17842922 TI - Color Phenomena. PMID- 17842924 TI - Detecting Antibodies to Penicillin. PMID- 17842923 TI - Letters to the Editor. PMID- 17842925 TI - Teaching "Science Learnings". PMID- 17842927 TI - Student Loyalty Oaths: Chances Nil for Outright Repeal; Compromise Possible. PMID- 17842926 TI - Government Organization of Science. PMID- 17842928 TI - Test Ban Research: Program Calls for More Than Double Planned Spending. PMID- 17842929 TI - Academy Radiation Committees Reassuring Reports. PMID- 17842930 TI - Civil Service Raises Pay for Scientists and Engineers. PMID- 17842931 TI - Form of the Pubic Bone in Neanderthal Man. AB - Shanidar I and III from Iraq have the same peculiar form of pubis as Tabun I from Palestine. These are the only such pubes known to exist. These facts suggest that Neanderthal man (Shanidar-Tabun) and an early variety of modern man (Skhul) coexisted during Mousterian times in this part of the world. PMID- 17842932 TI - Glacial Retreat in the North Bay Area, Ontario. AB - Geological and palynological studies in Ontario and Quebec, supported by radiocarbon dates, suggest that the opening of the North Bay outlet and the initiation of the Stanley-Chippewa stages in the Huron and Michigan basins took place 10,000 to 11,000 years ago. PMID- 17842933 TI - Science in Nigeria. PMID- 17842934 TI - Forthcoming Events. PMID- 17842935 TI - This Week in SCIENCE. PMID- 17842936 TI - Dendrimer research. PMID- 17842937 TI - Adjusting the 1990 census. PMID- 17842938 TI - Political savvy with connections. PMID- 17842939 TI - NRC Panel: Abolish Mandatory Retirement. PMID- 17842940 TI - Environmentalists: ban the (population) bomb. PMID- 17842942 TI - Jekyll and Hyde GAO? PMID- 17842941 TI - Britain picks wrong way to beat the Japanese. PMID- 17842943 TI - The graying of physics. PMID- 17842945 TI - Berg to Head NIH Genome Committee. PMID- 17842944 TI - Astro redux. PMID- 17842946 TI - The incredible shrinking tunneling microscope. PMID- 17842947 TI - The stately cycles of ancient climate. PMID- 17842948 TI - Rhino biology: keeping tabs on an endangered species: bursting bottlenecks. PMID- 17842949 TI - Rhino biology: keeping tabs on an endangered species: rhino rumbles. PMID- 17842950 TI - Rhino Biology: Keeping Tabs on an Endangered Species: Isotopic IDs for Rhino Horn. PMID- 17842951 TI - The potential for ozone depletion in the arctic polar stratosphere. AB - The nature of the Arctic polar stratosphere is observed to be similar in many respects to that of the Antarctic polar stratosphere, where an ozone hole has been identified. Most of the available chlorine (HCl and ClONO(2)) was converted by reactions on polar stratospheric clouds to reactive ClO and Cl(2)O(2) throughout the Arctic polar vortex before midwinter. Reactive nitrogen was converted to HNO(3), and some, with spatial inhomogeneity, fell out of the stratosphere. These chemical changes ensured characteristic ozone losses of 10 to 15% at altitudes inside the polar vortex where polar stratospheric clouds had occurred. These local losses can translate into 5 to 8% losses in the vertical column abundance of ozone. As the amount of stratospheric chlorine inevitably increases by 50% over the next two decades, ozone losses recognizable as an ozone hole may well appear. PMID- 17842952 TI - The response of electrons to structural changes. AB - The properties of a molecule are determined by the distribution of its electrons. This distribution can be described by the charge density, which is readily obtained from the wave functions derived by ab initio molecular orbital calculations. The charge density may be analyzed in a number of different fashions to give information about the effects of substituents, structural changes, and electronic excitation on the properties of molecules; one common procedure makes use of projection density or charge difference plots. Charge density also may be partitioned among atoms, and by numerical integration over appropriate volume elements one may obtain atomic charges, dipoles, kinetic energies, and other properties of the atoms in a molecule. Many chemical phenomena have been analyzed in terms of charge densities. PMID- 17842953 TI - Compressibility of solid c60. AB - Room-temperature powder x-ray diffraction profiles have been obtained at hydrostatic pressures P = 0 and 1.2 gigapascals on the solid phase of cubic C(60) ("fullerite"). Within experimental error, the linear compressibility d(ln a)/dP is the same as the interlayer compressibility d(ln c)/dP of hexagonal graphite, consistent with van der Waals intermolecular bonding. The volume compressibility d(ln V)/dP is 7.0 +/- 1 x 10(-12) square centimeter per dyne, 3 and 40 times the values for graphite and diamond, respectively. PMID- 17842954 TI - Spectroscopic observations of bright and dark emission features on the night side of venus. AB - Near-infrared spectra of a bright and a dark thermal emission feature on the night side of Venus have been obtained from 2.2 to 2.5 micrometers (microm) at a spectral resolution of 1200 to 1500. Both bright and dark features show numerous weak absorption bands produced by CO(2), CO, water vapor, and other gases. The bright feature (hot spot) emits more radiation than the dark feature (cold spot) throughout this spectral region, but the largest contrasts occur between 2.21 and 2.32 microm, where H(2)SO(4) clouds and a weak CO(2) band provide the only known sources of extinction. The contrast decreases by 55 to 65 percent at wavelengths longer than 2.34 microm, where CO, clouds, and water vapor also absorb and scatter upwelling radiation. This contrast reduction may provide direct spectroscopic evidence for horizontal variations in the water vapor concentrations in the Venus atmosphere at levels below the cloud tops. PMID- 17842955 TI - Proximate constraints on the evolution of egg size, number, and total clutch mass in lizards. AB - Proximate constraints on egg size, number, and total clutch mass in side-blotched lizards were examined by experimentally reducing average clutch size from 4.6 eggs to one, two, and three eggs. Eggs from experimentally altered clutches were larger than those from controls, reflecting the trade-off between egg size and number. Moreover, the increased frequency of females with oviducally bound eggs or eggs that burst at oviposition suggests that egg size in clutches with very few eggs are at a functional upper size limit. These proximate constraints may also limit evolution of egg size in another group of lizards (Anolis) that only produces one-egged clutches. PMID- 17842956 TI - A familiar mingling. PMID- 17842958 TI - Cryobiology. PMID- 17842957 TI - Nuclear reactions. PMID- 17842959 TI - Neutrons in a bottle. PMID- 17842960 TI - TRENDS IN ENGINEERING EDUCATION. PMID- 17842961 TI - JOHN ELIOT WOLFF. PMID- 17842962 TI - THE FISH AND WILDLIFE SERVICE. PMID- 17842963 TI - THE COLLEGE OF ENGINEERING OF CORNELL UNIVERSITY AND AMERICAN INDUSTRY. PMID- 17842964 TI - REPORT OF THE SUB-COMMITTEE OF THE AMERICAN INSTITUTE OF CHEMISTS ON LICENSING OF CHEMISTS IN NEW YORK STATE. PMID- 17842965 TI - THE PAN-AMERICAN CONGRESS OF OPHTHALMOLOGY AND OTOLARYNGOLOGY. PMID- 17842966 TI - A STANDARD EXPERIMENTAL VEGETATION TYPE. PMID- 17842967 TI - THE MUSEUM AS A POTENTIAL FORCE FOR SOCIAL ENLIGHTENMENT. PMID- 17842969 TI - COOPERATIVE INVESTIGATIONS OF THE RELATION BETWEEN MOSQUITO CONTROL AND WILDLIFE CONSERVATION. PMID- 17842968 TI - ELECTRODES SEALED IN GLASS TUBING. PMID- 17842970 TI - PANTOTHENIC ACID AND NUTRITIONAL ACHROMOTRICHIA IN RATS. PMID- 17842971 TI - CRYSTALLINE VITAMIN A PALMITATE AND VITAMIN A ALCOHOL. PMID- 17842972 TI - DUKE UNIVERSITY MEDICAL SCHOOL NORNICOTINE AS THE PREDOMINATING ALKALOID IN CERTAIN TOBACCOS. PMID- 17842973 TI - THE EFFECT OF SALICYLATE ON THE OXYGEN UPTAKE OF THE TUBERCLE BACILLUS. PMID- 17842974 TI - TATOO PUNCH FOR NUMBERING RATS. PMID- 17842975 TI - A TESTED METHOD OF GROWING STENTOR COERULEUS. PMID- 17842976 TI - Letter to the editor. PMID- 17842978 TI - The use of drugs. PMID- 17842977 TI - Letter to the editor. PMID- 17842979 TI - Technological advance. PMID- 17842981 TI - Increased pay, diminished stature. PMID- 17842980 TI - New maser at haystack. PMID- 17842982 TI - Isospin in Nuclei: Isospin has been reborn as an important and useful quantum number for all nuclei. AB - The major feature of isospin in nuclei that I have discussed here is its application to all nuclei. The rebirth of this quantum number in nuclear physics occurred in the early 1960's and was initiated almost entirely by the important work of Anderson et al. (4) and Fox et al. (5). There is still great interest in the use of isospin in its fullest sense as predicted by Wigner (3), and indeed isospin concepts have been largely responsible for demonstrating that nuclei in the doubly "magic number" region of (208)Pb are remarkably in agreement with shell model theory. The early experiments have also initiated a whole new set of more sophisticated experiments (some of which I have briefly alluded to above) which promise to keep many physicists busy for a long time to come. A particularly interesting series of experiments are those being performed (15) at Duke University with high-resolution proton beams. This work shows the highly detailed nature of analogue resonances, that is, as coherent superpositions of many complicated compound states yielding a beautifully modulated wave train, the modulation being observed only in conventional experiments with poor-resolution proton beams. Similarly, nuclear theorists have been led to vastly improve their interpretation of, and computational techniques for, both nuclear reactions and nuclear structure in order to meet the more stringent tests provided by such experiments. Perhaps a lesson can be learned from the historical development of the isospin concept. In the past the belief that T . T would not significantly commute with the dynamical Hamiltonian so that isospin would not be conserved sufficiently well enough certainly delayed the nuclear travels of isospin into the realm of heavy nuclei. Hopefully the same mistake will not occur in the future for other approximate symmetries of nature. PMID- 17842983 TI - Science Policy for the 1970's: Canada Debates the Options. PMID- 17842984 TI - Peer review system: how to hand out money fairly. PMID- 17842985 TI - David, PSAC Exit Predicted. PMID- 17842987 TI - Technological Initiatives: NBS Funds in Holding Pattern. PMID- 17842986 TI - AAAS Meeting: Policy Change on Activists Brings Police. PMID- 17842988 TI - Energy and the future: research priorities and national policy. PMID- 17842989 TI - Image of a sulfur atom. AB - Two-dimensional signal averaging has been applied to dark field electron micrographs of molecules of 2,3,4,5-tetraacetoxymercurithiophene. Only the mercury atom images are seen in single micrographs. However, in the composite image, resulting from photographic superposition of 64 individual images, the sulfur atom in the molecule is clearly revealed. PMID- 17842990 TI - Crystalline ordering in silica and germania glasses. AB - The diffraction patterns of both silica and germania glasses are consistent with a structure in which nearly all of the atoms belong to tridymite-like regions of up to about 20 angstroms or more that are bonded efficiently together in a manner analogous to that found in twinned crystals. PMID- 17842991 TI - High-Resolution Spectroscopy of the Earth's Free Oscillations, Knowing the Earthquake Source Mechanism. AB - A new method for identification of normal modes of oscillation of the earth yielded unambiguous determinations of many overtones never before identified. This method consists of the superposition of spectra observed at many stations over the earth, after a correction for the phase determined from the known earthquake source mechanism. PMID- 17842992 TI - Paleozoic seeds with embryos. AB - Seeds in a conifer cone from the Lower Permian of west Texas contain embryo tissue. These are the oldest plant embryos on record. Their development prior to seed dispersal shows that the sequence of embryo growth typical of most modern seed plants had evolved before the end of the Paleozoic Era. PMID- 17842993 TI - Prague international lead panel: effects of atmospheric lead on biological systems. PMID- 17842994 TI - Physical Thinking and Social Problems. PMID- 17842995 TI - An Intestinal Antiseptic: 2-Sulfanilamido-5-Carboxythiazole. PMID- 17842996 TI - Pectoral Girdles vs. Hyobranchia in the Snake Genera Liotyphlops and Anomalepis. PMID- 17842997 TI - Interrelations Between Choline, Betaine, and Methionine. PMID- 17842999 TI - Why H.R. 6448 Is the Better Bill. PMID- 17842998 TI - Why S. 1850 Is the Better Bill. PMID- 17843000 TI - Forum. PMID- 17843001 TI - Why I Am Biased in Favor of S. 1850. PMID- 17843002 TI - A United Front for S. 1850. PMID- 17843003 TI - Use of Wetting Agents in Histological Fixatives. PMID- 17843004 TI - A Modification of the Ergograph. PMID- 17843005 TI - The Metric System and the Historical Record. PMID- 17843006 TI - Relative to the B.S. Degree. PMID- 17843008 TI - A Dangerous Postwar Development in Science Teaching. PMID- 17843007 TI - Death-rate Study on a High Molecular Quaternary Ammonium Compound With Bacillus metiens. PMID- 17843009 TI - Aspergillus or What? PMID- 17843011 TI - U.s.-Chinese collaborations. PMID- 17843010 TI - Plagiarism in china. PMID- 17843012 TI - Paleoindians in the brazilian Amazon. PMID- 17843014 TI - Paleoindians in the brazilian Amazon. PMID- 17843013 TI - Paleoindians in the brazilian Amazon. PMID- 17843015 TI - Response: paleoindians in the brazilian Amazon. PMID- 17843016 TI - Response: DNA Looping and Lac Repressor--CAP Interaction. PMID- 17843017 TI - The loss of atmosphere from Mars. PMID- 17843018 TI - Response: the loss of atmosphere from Mars. PMID- 17843019 TI - Response: Alzheimer's Precursor Protein and the Use of Bathocuproine for Determining Reduction of Copper(II). PMID- 17843020 TI - ADDRESSES AT THE OPENING ASSEMBLY OF THE INTERNATIONAL UNION OF GEODESY AND GEOPHYSICS. PMID- 17843021 TI - OBITUARY. PMID- 17843022 TI - THE ORIGIN OF THE HUMAN RACES. PMID- 17843023 TI - THE FLOATING POPULATION OF THE AIR. PMID- 17843024 TI - THE RANGE OF HEARING OF CANARIES. PMID- 17843025 TI - A REQUEST TO MATHEMATICAL GENETICISTS. PMID- 17843026 TI - A POSSIBLE RELATION BETWEEN MANGANESE, SUNLIGHT AND WINTER HATCHABILITY OF HEN'S EGGS. PMID- 17843027 TI - THE SENSITIZING PROPERTIES OF THE NUCLEIC ACIDS AND THEIR DERIVATIVES. PMID- 17843028 TI - THE ELECTROPHORETIC ANALYSIS OF ANTIPNEUMOCOCCUS HORSE SERA. PMID- 17843029 TI - THE PHYSIOLOGICAL CHANGES PRODUCED IN YEAST BY ULTRA-VIOLET LIGHT AND BY HEAT. PMID- 17843030 TI - Nomenclature of Biological Devices. PMID- 17843031 TI - The Pharmacist and Poison Control. PMID- 17843032 TI - A Small Note of Cheer. PMID- 17843034 TI - U. S. Assistance to Latin America: Politics, Rather than Technology, Determines What Is Most Useful. PMID- 17843033 TI - Research on Handling Scientific Information. PMID- 17843035 TI - Four Major AAAS Awards Presented at Association's New York Meeting. PMID- 17843037 TI - Forthcoming Events. PMID- 17843038 TI - Bee language. PMID- 17843039 TI - Letters to the editor. PMID- 17843040 TI - Computers and human happiness. PMID- 17843041 TI - Sakharov on detente. PMID- 17843042 TI - Roszak and rationality. PMID- 17843043 TI - Letters to the editor. PMID- 17843044 TI - Declining years of hydrocarbon production. PMID- 17843045 TI - Residential patterns at monte alban, oaxaca, Mexico. AB - Monte Alban was founded in period I (about 500 B.C.) probably by households from previously existing villages in the Valley of Oaxaca. There is some evidence for status variation in period I households, but more information is needed to determine its role in the early development of the city. During the millennium or more of urban growth at Monte Alban a change occurred in the organization of household space from an open outward-directed focus to a closed inward-directed one. This was accompanied by a formalization of household and interhousehold space and by a standardization in household sizes and burial treatment reflecting emergence of a social class hierarchy. These changes indicate development from a flexible to a highly structured society, which may be a general trend in urbanization. PMID- 17843046 TI - Cliometrics: Book on Slavery Stirs up a Scholarly Storm. PMID- 17843047 TI - Son of deep throat foils physicists. PMID- 17843048 TI - Ford budget axe cuts research. PMID- 17843049 TI - Battelle memorial institute: another reading of the will. PMID- 17843050 TI - EPA Cites Errors in AEC's Reactor Risk Study. PMID- 17843051 TI - Exploring the Solar System (IV): What Future for Space Science? PMID- 17843052 TI - Fletcher Sees Major Thrust in Space Science in 1980's. PMID- 17843053 TI - Developmental neurobiology: specificity in the visual system. PMID- 17843054 TI - Science and the quality of our lives. PMID- 17843055 TI - Preconvention program. PMID- 17843056 TI - Tilt Precursors before Earthquakes on the San Andreas Fault, California. AB - An array of 14 biaxial shallow-borehole tiltmeters (at 1O(-7) radian sensitivity) has been installed along 85 kilometers of the San Andreas fault during the past year. Earthquake-related changes in tilt have been simultaneously observed on up to four independent instruments. At earthquake distances greater than 10 earthquake source dimensions, there are few clear indications of tilt change. For the four instruments with the longest records (> 10 months), 26 earthquakes have occurred since July 1973 with at least one instrument closer than 10 source dimensions and 8 earthquakes with more than one instrument within that distance. Precursors in tilt direction have been observed before more than 10 earthquakes or groups of earthquakes, and no similar effect has yet been seen without the occurrence of an earthquake. PMID- 17843057 TI - Aerosols in the atmosphere: calculation of the critical absorption/backscatter ratio. AB - The ratio of the absorption coefficient to the backscatter coefficient for which heating and cooling effects due to aerosols exactly balance at the earth's surface has been calculated with the use of a radiative-convective atmospheric model. The results are compared with those obtained from several simpler mean radiative-transfer models. PMID- 17843059 TI - PRODUCTS and MATERIALS. PMID- 17843058 TI - Sunday and workday variations in photochemical air pollutants in new jersey and new york. AB - Concentration distributions of air contaminants and meteorological variables in New Jersey and New York for workdays (Mondays through Fridays, omitting holidays) and Sundays are compared by means of quantile-quantile plots. The ozone distributions are slightly higher on Sundays, and the primary pollutant distributions are lower. These results raise serious questions about the validity of current concepts underlying ozone reduction in urban atmospheres. PMID- 17843060 TI - Erratum. AB - In the article "Panel says Depo-Provera not proved safe" (News and Comment, 23 Nov., p. 950), the dosages of Depo-Provera, a progestogen, and estrogens used in cancer therapy and as a contraceptive were incorrectly reported. In cancer therapy, the hormones are used in large doses. In contraceptives, the dosages are small. PMID- 17843061 TI - Chemical information online. PMID- 17843062 TI - Biological and chemical warfare. PMID- 17843063 TI - An Editor's Quest (I). PMID- 17843064 TI - Laser-induced fluorescence and bonding of metal dimers. AB - This article describes a technique for the spectroscopic of metal clusters and intermetallic compounds. First, metallic samples are vaporized by a pulsed YAG (yttrium-aluminum garnet) laser, and then the gaseous products are excited with a pulsed-dye laser until they fluoresce. A time-resolved, fluorescence spectrum is then measured by the product. The application of this technique to the study of metal dimers is reviewed, with emphasis on recent results from Be(2) and Cr(2). Studies of such species often yield insights into the chemistry of metals and metal-metal bonding. PMID- 17843065 TI - The 1984 nobel prize in physics. PMID- 17843066 TI - Restoration of the Humanities Urged: NEH chairman decries "garage sale" look of college curricula; says it's time to get back to the classics. PMID- 17843067 TI - New R&D Centers Will Test University Ties: Interdisciplinary research labs are campus fixtures, but industry, government involvement gives a new twist. PMID- 17843069 TI - Garrison compromise proposed. PMID- 17843068 TI - Industry-academia cooperation touted. PMID- 17843070 TI - A Rescue for Wisconsin's Synchrotron Source: Three years after its completion, Aladdin glows only feebly; to get more light out requires new NSF money and help from DOE accelerator experts. PMID- 17843071 TI - Microbiology: the microbe 1984. PMID- 17843072 TI - Planetary science: saturn. PMID- 17843073 TI - A naturalist of means: dear lord rothschild. PMID- 17843074 TI - Island biota: biogeography and ecoogy of the seychelles islands. PMID- 17843075 TI - The barbary macaque. PMID- 17843076 TI - Phytoplankton bloom produced by a receding ice edge in the ross sea: spatial coherence with the density field. AB - Measurements of chlorophyll, particulate carbon, and biogenic silica concentrations near a receding ice edge off the coast of Victoria Land, Antarctica, indicated the presence of a dense phytoplankton bloom. The bloom extended 250 kilometers from the ice edge and was restricted to waters where the melting of ice had resulted in reduced salinity. The region involved was one of enhanced vertical stability, which may have favored phytoplankton growth, accumulation, or both. Epontic algae released from melting ice may have served as an inoculum for the bloom. Ratios of organic carbon to chlorophyll and biogenic silica to carbon were unusually high, resulting in high biogenic silica concentrations despite only moderately high chlorophyll levels. PMID- 17843077 TI - Do frogs communicate with seismic signals? AB - Male white-lipped frogs exhibit conspicuous behavioral responses to calling conspecific males that are nearby but out of view. Since the calls often are accompanied by strong seismic signals (thumps), and since the male white-lipped frog exhibits the most acute sensitivity to seismic stimuli yet observed in any animal, these animals may use seismic signals as well as auditory signals for intraspecific communication. PMID- 17843078 TI - Dinoflagellate with blue-green chloroplasts derived from an endosymbiotic eukaryote. AB - The dinoflagellate, Amphidinium wigrense, contains triple membrane-bound bodies we have termed "blue-green chloroplasts." We believe these chloroplasts were derived from a cryptomonad endosymbiont similar to that present in another blue green dinoflagellate, Gymnodinium acidotum. These dinoflagellates provide evidence that a chloroplast has evolved from an endosymbiotic eukaryote. PMID- 17843079 TI - THE PUBLICATION OF SCIENTIFIC AND TECHNICAL MATERIAL BY THE UNITED STATES DEPARTMENT OF AGRICULTURE. PMID- 17843080 TI - DISCUSSION OF SOME ASPECTS IN THE PUBLICATION OF GOVERNMENT RESEARCH. PMID- 17843081 TI - ALBERT LLOYD BARROWS 1883-1942. PMID- 17843082 TI - TUFTS COLLEGE CHAPTER OF THE SOCIETY OF THE SIGMA XI. PMID- 17843084 TI - SUMMER SESSION IN APPLIED MATHEMATICS AT BROWN UNIVERSITY. PMID- 17843083 TI - THE COLUMBUS MEETING OF THE AMERICAN PHYSICAL SOCIETY. PMID- 17843085 TI - ELECTION OF FELLOWS OF THE ROYAL SOCIETY. PMID- 17843086 TI - FIRST CHARLES L. MAYER AWARD OF THE NATIONAL SCIENCE FUND. PMID- 17843087 TI - MEDAL DAY OF THE FRANKLIN INSTITUTE, PHILADELPHIA. PMID- 17843088 TI - THE COMPLEX VITAMIN B COMPLEX. PMID- 17843089 TI - THE WORK OF SOVIET BOTANISTS. PMID- 17843090 TI - EARLY AND LATE EASTER DATES. PMID- 17843091 TI - PHENOTHIAZINE FOR CATTLE LICE CONTROL. PMID- 17843092 TI - ENZYME SYSTEMS CONTAINING ACTIVE SULFHYDRYL GROUPS. THE ROLE OF GLUTATHIONE. PMID- 17843093 TI - AUXIN ACTION. PMID- 17843094 TI - A RAPID AND ACCURATE MICRO METHOD FOR THE ESTIMATION OF THE SULFONAMIDES. PMID- 17843095 TI - EUROE DURING AND AFTER THE ICE AGE. PMID- 17843096 TI - TREATMENT OF FUNGOUS DISEASES. PMID- 17843097 TI - SCHOOL OF APPLIED ETHICS, SUMMER SESSION. PMID- 17843098 TI - HEALTH MATTERS. PMID- 17843099 TI - The Horned Saurians of the Laramie Formation. PMID- 17843100 TI - Iroquoian Etymologies. PMID- 17843101 TI - The Shrike. PMID- 17843102 TI - A Double Motion of Clouds. PMID- 17843103 TI - THE SMITHSONIAN INSTITUTION AND THE NATIONAL MUSEUM. PMID- 17843104 TI - THE GEOLOGY OF GOVERNMENT EXPLORATIONS. PMID- 17843105 TI - PROFESSOR EUGEN BAUMANN. PMID- 17843106 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17843107 TI - ALFRED TRESCA. PMID- 17843108 TI - THE DAVY-FARADAY RESEARCH LABORATORY. PMID- 17843109 TI - THE MARINE BIOLOGY OF GREAT BRITAIN. PMID- 17843110 TI - CLOUDS OVER A FIRE. PMID- 17843111 TI - VOLCANIC DUST IN SOUTHWESTERN NEBRASKA AND IN SOUTH DAKOTA. PMID- 17843112 TI - COMPLIMENT OR PLAGIARISM? PMID- 17843113 TI - THE VARIATION OF TEMPERATURE UNDER CONDITIONS PRESUMABLY THE SAME. PMID- 17843114 TI - DISTRIBUTION OF PUBLIC DOCUMENTS. PMID- 17843115 TI - HISTORY OF THE APPLICATION OF THE ELECTRIC LIGHT TO LIGHTING THE COASTS OF FRANCE. PMID- 17843116 TI - INDIAN RELICS FROM NEW BRUNSWICK. PMID- 17843117 TI - GEOLOGICAL NOMENCLATURE AND COLORING. PMID- 17843118 TI - THE PROPERTIES OF CARDIAC MUSCLE, AND THE NATURE OF THE ACTION OF THE VAGUS NERVE UPON THE HEART. PMID- 17843119 TI - THERMOMETER EXPOSURE. PMID- 17843121 TI - Radiant heat, and the second law of thermodynamics. PMID- 17843120 TI - Keweenaw-point geology. PMID- 17843122 TI - Badly crystallized wrought iron. PMID- 17843123 TI - Caterpillars eaten by a kitten. PMID- 17843124 TI - Cracking in ice. PMID- 17843125 TI - Apparent attractions and repulsions of small floating bodies. PMID- 17843126 TI - Domestic ducks that fly abroad like pigeons. PMID- 17843127 TI - HOUGHTON FARM EXPERIMENTS. PMID- 17843128 TI - A new lecture experiment. PMID- 17843129 TI - FOSSIL ALGAE. PMID- 17843130 TI - BOLTON'S QUANTITATIVE ANALYSIS. PMID- 17843131 TI - INTELLIGENCE FROM AMERICAN SCIENTIFIC STATIONS. PMID- 17843132 TI - SCIENCE NEWS. PMID- 17843133 TI - SCIENCE AND SCIOSOPHY. PMID- 17843134 TI - MEDICAL EDUCATION AND CULTURE. PMID- 17843135 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17843136 TI - THE ENCYSTMENT OF VAMPYRELLA ELEGANS (H. AND L.). PMID- 17843137 TI - POISONING FROM CASTOR BEANS. PMID- 17843139 TI - UNIVERSITIES AND THE CIRCUS. PMID- 17843138 TI - WOMEN OFFICERS OF THE ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17843140 TI - AN INTERPRETATION OF ORTHOGENESIS. PMID- 17843141 TI - THE SURFACE EQUILIBRIUM OF COLLOIDAL SOLUTIONS AND THE DIMENSIONS OF SOME COLLOIDAL MOLECULES. PMID- 17843142 TI - DIVISION OF ORGANIC CHEMISTRY. PMID- 17843144 TI - THE MEETING IN GENERAL. PMID- 17843143 TI - SCIENCE NEWS. PMID- 17843145 TI - REGISTRATION. PMID- 17843147 TI - SOCIAL FUNCTIONS. PMID- 17843146 TI - MEETINGS OF THE COUNCIL. PMID- 17843148 TI - SECTION A (MATHEMATICS). PMID- 17843149 TI - SECTION B (PHYSICS). PMID- 17843150 TI - SECTION C (CHEMISTRY). PMID- 17843151 TI - SECTION D (ASTRONOMY). PMID- 17843152 TI - SECTION E (GEOLOGY AND GEOGRAPHY). PMID- 17843154 TI - SECTION F (ZOOLOGICAL SCIENCES). PMID- 17843153 TI - SECTION G (BOTANICAL SCIENCES). PMID- 17843155 TI - SECTION I (PSYCHOLOGY). PMID- 17843156 TI - SECTION H (ANTHROPOLOGY). PMID- 17843157 TI - SECTION K (SOCIAL AND ECONOMIC SCIENCES). PMID- 17843158 TI - SECTION L (HISTORICAL AND PHILOLOGICAL SCIENCES). PMID- 17843159 TI - SECTION N (MEDICAL SCIENCES). PMID- 17843161 TI - SECTION O (AGRICULTURE). PMID- 17843160 TI - SECTION Q (EDUCATION). PMID- 17843162 TI - THE BASIC MECHANISMS OF STATIC ELECTRIFICATION. PMID- 17843163 TI - THE BIOCHEMISTRY OF MUSCLE TRAINING. PMID- 17843164 TI - GEORGE DAVID BIRKHOFF. PMID- 17843165 TI - THE PROMOTION OF SCIENCE BY THE GOVERNMENT. PMID- 17843166 TI - ROYAL SOCIETY MEDALISTS. PMID- 17843167 TI - SCIENCE AWARDS OF THE GUGGENHEIM FOUNDATION. PMID- 17843168 TI - RECENT GIFTS TO THE ARNOLD ARBORETUM OF HARVARD UNIVERSITY. PMID- 17843169 TI - REPORT OF GENERAL ARNOLD ON THE NEED FOR MAINTAINING ADEQUATE AIR POWER. PMID- 17843170 TI - NEWS FROM ABROAD. PMID- 17843171 TI - THE AMERICAN ACADEMY OF TROPICAL MEDICINE. PMID- 17843172 TI - THE ROLE OF AMINO ACIDS AND AMIDES IN THE METABOLISM OF AMMONIUM ABSORBED BY ZEA MAYS L. AB - When corn seedlings, previously depleted in soluble nitrogen constituents, are forced to absorb large quantities of ammonium nitrogen, soluble compounds accumulate in the sap. Asparagine, glutamine, one or more amino acids and undetermined compounds are synthesized. Ammonia does not accumulate until these constituents have reached a relatively high level. PMID- 17843173 TI - THE EFFECT OF TRANSFUSIONS OF RED BLOOD CELLS ON THE HYPOXIA TOLERANCE OF NORMAL MEN. PMID- 17843174 TI - CYTOPLASMIC DISEASES AND CANCER. PMID- 17843175 TI - AN ANTIBIOTIC FROM A BEE PATHOGEN. PMID- 17843176 TI - THE CONTINUOUS CULTIVATION OF MICRO-ORGANISMS. PMID- 17843177 TI - THE AMERICAN PHILOSOPHICAL SOCIETY. PMID- 17843179 TI - AN APPEAL FOR AID TO THE PHILIPPINE BUREAU OF FISHERIES. PMID- 17843178 TI - THE SMALL MOUNDS OF THE GULF COASTAL PLAIN. PMID- 17843180 TI - AN UNUSUAL ACTION OF AMPHETAMINE. PMID- 17843182 TI - Viet Nam and the Professors. PMID- 17843181 TI - Letters to the Editor. PMID- 17843183 TI - Lullaby for Male Voices. PMID- 17843184 TI - Rank Discrimination. PMID- 17843185 TI - The Productive Lnvironment for Innovation. PMID- 17843186 TI - Strong Inference and Weak Interactions. PMID- 17843188 TI - Indirect Costs: House Legislation Embodies New Cost-Sharing Formula for Federal Research Grants. PMID- 17843187 TI - Stony Brook: Young and Ambitious New York Institution Is Beginning To Stir Notice in Academic World. PMID- 17843189 TI - Germanium and Silicon Disulfides: Structure and Synthesis. AB - Crystal structures of the tetragonal forms of germanium and silicon disulfide are similar and consist of (SiS(4))(4-) and (GeS(4))(4-) tetrahedra which share vertices to form three-dimensional networks. These tetragonal materials, synthesized at high pressure and temperature, are different from the previously known germanium and silicon disulfides. PMID- 17843190 TI - Desert Locusts: Sexual Maturation Delayed by Feeding on Senescent Vegetation. AB - A diet of senescent Brassica spp. delayed sexual maturation in the desert locust. The senescent leaves were shown to be short of gibberellins, and a dietary supplement of gibberellin A(3) (1 microgram per locust per day) restored the rate of maturation to that found in animals feeding on green leaves. An external application of eugenol had a similar effect. The sexual immaturity of desert locusts during the dry season may result from the senescent condition of their desert food plants. PMID- 17843191 TI - Roots as Organs of Assimilation of Sulfate. AB - Roots of the field pea (Pisum arvense L.) can reduce a small proportion of the sulfate that they absorb from the external medium. Some of this reduced sulphur is transported to the shoot as methionine and, to a lesser extent, as cysteine and glutathione. PMID- 17843192 TI - Sound Production by Cichlid Fishes. AB - Adults of three cichlid species, Hemichromis bimaculatus Gill, Cichlasoma nigrofasciatum (Gunther), and Pterophyllum sp., produce sounds of apparent biological significance. Both sexes of H. bimaculatus produce sounds, but whether both sexes in the other species produce sounds has not been established. The most intense tone frequencies in H. bimaculatus and C. nigrofasciatum lie generally between 300 and 500 cycles per second. The sound produced by Pterophyllum sp., however, has a broad maximum intensity around 3500 cycles per second and component frequencies over 10,000 cycles per second. Sound production appears to depend on the aggressiveness of the individual. PMID- 17843193 TI - Orientation of Ambystoma maculatum: Movements to and from Breeding Ponds. AB - Migrating Ambystoma maculatum tend to utilize the same track on entering and leaving breeding ponds. The movements are usually accom plished at night in rain, fog, or cloudy, weather when visible celestial cues may not be available. The sensory basis for the orienting ability is unknown. PMID- 17843194 TI - Changes in the Tail Feathers of the Adolescent Lyrebird. PMID- 17843195 TI - Forthcoming Events. PMID- 17843196 TI - Tsunami Runup: United States Japan Cooperative Science Program. PMID- 17843197 TI - American Institute of Human Paleontology. PMID- 17843198 TI - Meetings & Conferences. PMID- 17843199 TI - Chelating Agents and Plant Nutrition. PMID- 17843201 TI - Miscellaneous Publications. PMID- 17843200 TI - Analysis of Uranium in Sea Water. PMID- 17843202 TI - A Note on the Flagellation of Phytophthora infestans (Mont.) deBary. PMID- 17843203 TI - Carbon Dioxide Compensation Point in Photosynthesis. PMID- 17843204 TI - Simple Method of Measuring Opaque Objects. PMID- 17843205 TI - This Week in SCIENCE. PMID- 17843207 TI - Sciencescope. PMID- 17843206 TI - Response. PMID- 17843208 TI - The second detector: starting from scratch? PMID- 17843210 TI - SSC Savaged by Soundbites. PMID- 17843209 TI - Showdown at the waxahachie corral. PMID- 17843212 TI - IOM Elects New Members. PMID- 17843211 TI - Was underwater "shot" harmful to the whales? PMID- 17843213 TI - How about men only for Mars? PMID- 17843214 TI - Slugging It Out Over Left-handed Mortality. PMID- 17843215 TI - Digital harvest. PMID- 17843216 TI - GAO Questions Census Adjustment. PMID- 17843217 TI - Thier to head brandeis. PMID- 17843219 TI - The eating right pyramid. PMID- 17843218 TI - Crowded dial. PMID- 17843220 TI - Animal rights food groups. PMID- 17843221 TI - A "new look" for archeology. PMID- 17843222 TI - Remote Sensing in War's Aftermath. PMID- 17843223 TI - Making waves with interfering atoms. PMID- 17843224 TI - Shine on, holey silicon. PMID- 17843225 TI - Putting some spark in silicon. PMID- 17843226 TI - Core formation during early accretion of the Earth. AB - Recent studies are leading to a better understanding of the formation of the earth's metal core. This new information includes: better knowledge of the physics of metal segregation, improved geochemical data on the abundance of siderophile and chalcophile elements in the silicate part of the earth, and experimental data on the partitioning behavior of siderophile and chalcophile elements. Extensive melting of the earth as a result of giant impacts, accretion, or the presence of a dense blanketing atmosphere is thought to have led to the formation of the core. Collision between a planet-sized body and the earth may have also produced the moon. Near the end of accretion, core formation evidently ceased as upper mantle conditions became oxidizing. The accumulation of the oceans is a consequence of the change to oxidizing conditions. PMID- 17843227 TI - Epitaxial cuprate superconductor/ferroelectric heterostructures. AB - Thin-film heterostructures of Bi(4)Ti(3)O(12)Bi(2)Sr(2)CuO(6+x), have been grown on single crystals of SrTiO(3), LaAlO(3), and MgAl(2)O(4) by pulsed laser deposition. X-ray diffraction studies show the presence of c-axis orientation only; Rutherford backscattering experiments show the composition to be close to the nominal stoichiometry. The films are ferroelectric and exhibit a symmetric hysteresis loop. The remanent polarization was 1.0 microcoulomb per square centimeter, and the coercive field was 2.0 x 10(5) volts per centimeter. Similar results were obtained with YBa(2)Cu(3)O(7-x) and Bi(2)Sr(2)CaCu(2)O(8+x), and single-crystal Bi(2)Sr(2)CuO(6+x)as the bottom electrodes. These films look promising for use as novel, lattice-matched, epitaxial ferroelectric film/electrode heterostructures in nonvolatile memory applications. PMID- 17843228 TI - Calcic micas in the allende meteorite: evidence for hydration reactions in the early solar nebula. AB - Two calcic micas, clintonite and margarite, have been identified in alteration products in a calcium- and aluminum-rich inclusion (CAI) in the Allende meteorite. Clintonite replaces grossular in alteration veins, and margarite occurs as lamellae in anorthite. Their occurrence suggests that, in addition to undergoing high-temperature alteration by a volatile and iron-rich vapor that produced the grossular and anorthite, some CAIs underwent alteration at moderate temperatures (2.6 x 10(9) years) of these eclogites and their stratigraphic position on the geotherm, it is proposed that the inflected part of the geotherm represents the convective boundary layer beneath the conductive lid of the lithospheric plate. The gradient of 8 Celsius degrees per kilometer for the inflection is characteristic of a double thermal boundary layer and suggests layered convection rather than whole mantle convection for the earth. PMID- 17843358 TI - A methanotrophic marine molluscan (bivalvia, mytilidae) symbiosis: mussels fueled by gas. AB - An undescribed mussel (family Mytilidae), which lives in the vicinity of hydrocarbon seeps in the Gulf of Mexico, consumes methane (the principal component of natural gas) at a high rate. The methane consumption is limited to the gills of these animals and is apparently due to the abundant intracellular bacteria found there. This demonstrates a methane-based symbiosis between an animal and intracellular bacteria. Methane consumption is dependent on the availability of oxygen and is inhibited by acetylene. The consumption of methane by these mussels is associated with a dramatic increase in oxygen consumption and carbon dioxide production. As the methane consumption of the bivalve can exceed its carbon dioxide production, the symbiosis may be able to entirely satisfy its carbon needs from methane uptake. The very light (delta(13)C = -51 to -57 per mil) stable carbon isotope ratios found in this animal support methane (delta(13)C = -45 per mil at this site) as the primary carbon source for both the mussels and their symbionts. PMID- 17843359 TI - Bacterivory: a novel feeding mode for asteroid larvae. AB - Planktotrophic larvae that occur beneath the annual sea ice in the Antarctic assimilate organic solutes and preferentially ingest bacteria, whereas they actively exclude phytoplankton. In regions where phytoplankton biomass is temporally limited by light or nutrient concentrations, the growth and development of planktotrophic larvae may not be directly coupled to phytoplankton production. PMID- 17843361 TI - National forum for school science: forum '86: the science curriculum. PMID- 17843360 TI - Oceanic dimethylsulfide: production during zooplankton grazing on phytoplankton. AB - About half the biogenic sulfur flux to the earth's atmosphere each year arises from the oceans. Dimethylsulfide (DMS), which constitutes about 90% of this marine sulfur flux, is presumed to originate from the decomposition of dimethylsulfoniopropionate produced by marine organisms, particularly phytoplankton. The rate of DMS release by phytoplankton is greatly increased when the phytoplankton are subjected to grazing by zooplankton. DMS production associated with such grazing may be the major mechanism of DMS production in many marine settings. PMID- 17843362 TI - Lectins: microbial lectins and agglutinins. PMID- 17843363 TI - Demonstrating natural selection: natural selection in the wild. PMID- 17843364 TI - Riverine mammals: otters. PMID- 17843365 TI - Solar physics: progress in solar physics. PMID- 17843367 TI - SCIENCE NEWS. PMID- 17843366 TI - Products & materials. PMID- 17843368 TI - THE LAND UTILIZATION PROGRAM IN THE SOUTHERN GREAT PLAINS. PMID- 17843369 TI - ON THE CITATION OF AUTHORITIES FOR BOTANICAL NAMES. PMID- 17843370 TI - LIGHT EYES AND GLARE SENSITIVITY. PMID- 17843371 TI - BACTERIAL-PLANT GROUP OF DHAINCHA. PMID- 17843372 TI - SYMPOSIUM ON MENTAL HEALTH. PMID- 17843373 TI - RECOVERY OF EASTERN EQUINE ENCEPHALOMYELITIS VIRUS FROM BRAIN TISSUE OF HUMAN CASES OF ENCEPHALITIS IN MASSACHUSETTS. PMID- 17843374 TI - THE PRODUCTION OF A GONADOTROPHIC SUBSTANCE (PROLAN) BY PLACENTAL CELLS IN TISSUE CULTURE. PMID- 17843375 TI - THE COLD WATER LAYER OF THE SCOTIAN SHELF. PMID- 17843376 TI - Financing Cancer Research. PMID- 17843377 TI - Scientific Development of the Use of Human Resources: Progress in the Army Air Forces. PMID- 17843379 TI - The Polished Rocks of Cornudas Mountain, New Mexico. PMID- 17843378 TI - Vitamin C Content of Mexican Ornamental Plants. PMID- 17843380 TI - The Movement of Substances Through a Two-phased Solution System. AB - The tendencies for movement of either solvent or solute in solution through a two phased system are expressed in terms of specific (volumed) free energies. These are based on the concept of escaping tendency or free energy of a constituent component of a solution. This scheme is particularly useful to the biologist for evaluating the movement of water and solutes into cells or organs. PMID- 17843381 TI - Experimental Argyrosis: II. Treatment of Rats Receiving Silver With 2,3 Dimercaptopropanol (BAL). PMID- 17843382 TI - The Effect of Streptomycin on the Oxygen Uptake of Eberthella typhosa. PMID- 17843383 TI - Autolyzed Brain Tissue as a Means of Facilitating Transmission of Experimental Poliomyelitis. AB - Autolyzed brain tissue diluent shortens the incubation period and facilitates the transfer of poliomyelitis virus to CFW Swiss mice, hamsters, and rhesus monkeys. The Leon monkey-passage strain of poliomyelitis virus was successfully adapted to CFW Swiss mice by means of this technic. Since this manuscript was submitted we have isolated several strains of poliomyelitis virus from infected human feces and spinal cord in CFW Swiss mice by means of this technic. PMID- 17843384 TI - The Assay of New Rich Natural Sources of Ascorbic Acid. PMID- 17843385 TI - Semiquantitative Determination of Traces of Uranium: A Fluorophotometric Method for Field Use. PMID- 17843386 TI - A Simple Resistance Thermometer for Blood-Temperature Measurements. PMID- 17843387 TI - The Cultivation of Mammalian Liver Cells in Large Numbers. PMID- 17843388 TI - A Question about !Kung Ecology. PMID- 17843390 TI - Cancer congress boycott. PMID- 17843391 TI - Spark discharge: application multielement spectrochemical analysis. AB - Spark discharge is shown to be a cyclic process of energy dissipation, with one spark in a time-connected train influenced by its relation to predecessor sparks. Spectroscopic instruments having temporal, spatial, and spectral resolution indicate that the light emission is highly ordered with cylindrical symmetry about the current-conducting spark channel. The favored spatial coincidence is between the channel and the most highly ionized and most excited species sampled from the cathode, with less ionized and less excited species emitting farther outward. Light absorption occurs to such an extent that there are full line reversals in excited states of magnesium ions, distant from the channel. Schlieren data indicate a toroidal structure in the postdischarge environment. Charge transfer, Penning ionization, and sensitized fluorescence are thought to be the chemical mechanisms responsible for the spectroscopic topography. Experiments in spectrochemical analysis based on the topography and designed for increased sensitivity, reduced matrix effects, and simpler spectra are discussed. PMID- 17843392 TI - Interdisciplinary education: a continuing experiment. PMID- 17843393 TI - Minerals and mining: major review of federal policy is in prospect. PMID- 17843394 TI - NASA Study Was Bust, Not Boost, Says Proxmire. PMID- 17843395 TI - If You Can't Beat Them, Join Them. PMID- 17843396 TI - Georgia dam collapse renews concern for safety. PMID- 17843397 TI - Erratum. AB - Due to a last minute printer's error, the 18 November Table of Contents omitted mention of a Research News article on "The 1977 Nobel Prize in chemistry" by I. Procaccia and J. Ross. PMID- 17843398 TI - The 1977 nobel prize in economics. PMID- 17843399 TI - Prospectuses of neurobiology. PMID- 17843400 TI - Cognitive psychology. PMID- 17843401 TI - North american archeology. PMID- 17843402 TI - Biological gerontology. PMID- 17843403 TI - Ganglionic cells. PMID- 17843404 TI - Mercury dispersal from lode sources in the kuskokwim river drainage, alaska. AB - The Kuskokwim River is not industrially polluted, but it does have an anomalous mercury content due to cinnabar particles in bottom sediments near natural mineralized sources; the mercury content is rapidly diluted downstream by physical mixing with other sediments. Mercury anomalies extend the greatest distance downstream in the tributaries, the finest size fraction of bottom sediment, the river-bank deposits, the suspended sediment, and water; the last two of these categories contribute the bulk of the mercury to the marine environment. PMID- 17843405 TI - Anomalous solar rotation in the early 17th century. AB - The character of solar rotation has been examined for two periods in the early 17th century for which detailed sunspot drawings are available: A.D. 1625 through 1626 and 1642 through 1644. The first period occurred 20 years before the start of the Maunder sunspot minimum, 1645 through 1715; the second occurred just at its commencement. Solar rotation in the earlier period was much like that of today. In the later period, the equatorial velocity of the sun was faster by 3 to 5 percent and the differential rotation was enhanced by a factor of 3. The equatorial acceleration with declining solar activity is in the same sense as that found in recent Doppler data. It seems likely that the change in rotation of the solar surface between 1625 and 1645 was associated with the onset of the Maunder Minimum. PMID- 17843407 TI - Panhandling as an example of the sharing of resources. PMID- 17843406 TI - Sedimentary polycyclic aromatic hydrocarbons: the historical record. AB - Polycyclic aromatic hydrocarbons in three sections of a dated sediment core from Buzzards Bay, Massachusetts, have been analyzed by gas chromatographic spectrometry. This historical information suggests that sedimentary polycyclic aromatic hydrocarbons, at least at this location, result primarily from the anthropogenic combustion of fossil fuels. PMID- 17843408 TI - Panhandling as an example of the sharing of resources. PMID- 17843409 TI - Wiley Pure Food Laws--a 50th Anniversary. PMID- 17843410 TI - Molecular Organization of Genetic Material. PMID- 17843411 TI - Lamont Natural Radiocarbon Measurements III. PMID- 17843412 TI - Hans Geiger: Fiftieth Anniversary of the Publication of His Doctoral Thesis, 23 July 1906. PMID- 17843413 TI - News of Science. PMID- 17843414 TI - Genetic Effects of Atomic Radiation: Committee on Genetic Effects of Atomic Radiation. AB - In the report of the Committee on Genetic Effects of Atomic Radiation, which appeared in the 29 June issue, the number "200 million children" in line 18 of the third column on page 1163 is an error. The question should read: "What is the estimate of the total number of mutants which would be induced by this radiation dose and passed on to the next total generation of about 100 million children?" PMID- 17843415 TI - Enzymatic Oxidation of Glucose to Glucosone in a Red Alga. PMID- 17843416 TI - Hardness of Substances in the Ideal State. PMID- 17843417 TI - "Clock" Controlled Activity Rhythms in the Fruit Fly. PMID- 17843418 TI - Ratio of Ionium to Uranium in Coral Limestone. PMID- 17843419 TI - Rapid Ion-Exchange Method for Determining Total Fluoride in Impure KF {middle dot} HF. PMID- 17843420 TI - Multiple Glaciation since the Ice Age. PMID- 17843421 TI - Penetration of Slow Electrons through Spore Walls of Bacillus megaterium. PMID- 17843422 TI - Miscellaneous Publications. PMID- 17843425 TI - Equipment News. PMID- 17843424 TI - Meetings and Societies. PMID- 17843426 TI - SCIENCE NEWS. PMID- 17843427 TI - THE APPLICATION OF ENGINEERING TO THE AGRICULTURAL INDUSTRY. PMID- 17843428 TI - THE GOVERNMENT MAPPING PROGRAM IN A MAP-MINDED AGE. PMID- 17843429 TI - RENEWAL OF THE AMERICAN MUSEUM EXPLORATIONS IN THE GOBI DESERT. PMID- 17843430 TI - AUSTRALOPITHECUS NOT A CHIMPANZEE. PMID- 17843431 TI - THE NATIVITY OF THE PUMPKINS. PMID- 17843432 TI - STRIATED COBBLES FROM TEAY VALLEY, WEST VIRGINIA. PMID- 17843433 TI - STARLINGS IN OKLAHOMA. PMID- 17843434 TI - FRUIT AND VEGETABLE PIGMENTS AS INDICATORS. AB - (1) Solutions of many fruit pigments act as indicators. (2) These solutions are easily prepared and stable, and the pH range of their color changes is in most cases conveniently near the neutral point (3) As liquid indicators they can be used in titrating acids, but not bases (4)Their greatest usefulness depends upon the fact that very satisfactory test papers can be made with them in a simple and inexpensive way. PMID- 17843435 TI - THE SPOTTING METHOD OF WEED ERADICATION. PMID- 17843436 TI - CAPACITY OF CONDENSERS IN SERIES. PMID- 17843437 TI - FURTHER OBSERVATIONS ON ADRENALECTOMIZED CATS TREATED WITH AN AQUEOUS EXTRACT OF THE SUPRARENAL CORTEX. PMID- 17843438 TI - CERTAIN BIOLOGICAL EFFECTS OF HIGH FREQUENCY FIELDS. PMID- 17843439 TI - ON THE ALLEGED MONGOLIAN AFFINITIES OF THE AMERICAN RACE. PMID- 17843440 TI - ON THE CAUSES OF VARIATION IN ORGANIC FORMS. PMID- 17843441 TI - SCHOOL OF BIOLOGY, UNIVERSITY OF VIRGINIA. PMID- 17843443 TI - A MAGNETIC SURVEY OF JAPAN. PMID- 17843442 TI - THE ERUPTION OF BANTAISAN. PMID- 17843444 TI - THE ELECTRIC-LIGHT CONVENTION. PMID- 17843445 TI - SCIENTIFIC NEWS IN WASHINGTON. PMID- 17843446 TI - Disinfectants that neutralize Each Other. PMID- 17843447 TI - An International Marine Conference. PMID- 17843448 TI - EXPLORATION AND TRAVEL. PMID- 17843450 TI - The Limit of Drift. PMID- 17843449 TI - A Brilliant Meteor. PMID- 17843451 TI - Mississagua Etymology. PMID- 17843453 TI - THE SEMBLING OF A LARGE NATIVE MOTII, TELEA, POLYPHEMUS. PMID- 17843452 TI - THE IMPORTANCE OF STRUCTURAL DETAILS IN THE STUDY OF PLANTS. PMID- 17843454 TI - NATIONAL PARK PROTECTIION. PMID- 17843456 TI - SCIENTIFIC WASHINGTON. PMID- 17843455 TI - IS GRANITE EVER METAMORPHIC? PMID- 17843457 TI - THE EMPLOYMENT OF DISEASE-CAUSING MICROBES FOR THE DESTRUCTION OF FIELD MICE, MOLES AND SIMILAR, VERMIN. PMID- 17843458 TI - GOLDEN SANDS OF THE PACIFIC COAST. PMID- 17843459 TI - THE SELF-PURIFICATION OF RIVERS. PMID- 17843460 TI - Paleolithic Pottery. PMID- 17843461 TI - The Swastika Cross. PMID- 17843462 TI - A Miniature Water Lily. PMID- 17843463 TI - Mr. MacDougal and Poisoning from Cypripedium spectabile. PMID- 17843464 TI - The Durability of the Poisonous Property of Poison Ivy, Rhus Radicans L. (R. Toxicodendron L.). PMID- 17843465 TI - A Brilliant Aurora. PMID- 17843466 TI - Nature Study in the Schools. PMID- 17843467 TI - A New Dicotyline Mammal from the Kansas Pliocene. PMID- 17843468 TI - This week in science. PMID- 17843469 TI - Response. PMID- 17843470 TI - Aerosols and global warming. PMID- 17843471 TI - Response. PMID- 17843472 TI - Household Composition and Children's Income. PMID- 17843474 TI - Fusion reactor infusion at princeton. PMID- 17843473 TI - E-Mail Links Science's Young and Frustrated. PMID- 17843476 TI - Out of adversity, new clues to prairie diversity. PMID- 17843475 TI - Wanted: digital or analog. PMID- 17843477 TI - Long odds against landing a math job. PMID- 17843478 TI - Liquids do the quasicrystal twist. PMID- 17843479 TI - Researchers give fullerenes gas. PMID- 17843481 TI - Academy Weighs in on EOS Data System. PMID- 17843480 TI - New words from the wise. PMID- 17843482 TI - COBE Finds the Bumps in the Big Bang. PMID- 17843484 TI - Virtual acoustics puts sound in its place. PMID- 17843483 TI - A Dubious Battle to Save the Kemp's Ridley Sea Turtle. PMID- 17843485 TI - Raising water to new heights. PMID- 17843486 TI - Shaking Arabidopsis thaliana. PMID- 17843487 TI - Colloid formation during waste form reaction: implications for nuclear waste disposal. AB - Insoluble plutonium- and americium-bearing colloidal particles formed during simulated weathering of a high-level nuclear waste glass. Nearly 100 percent of the total plutonium and americium in test ground water was concentrated in these submicrometer particles. These results indicate that models of actinide mobility and repository integrity, which assume complete solubility of actinides in ground water, underestimate the potential for radionuclide release into the environment. A colloid-trapping mechanism may be necessary for a waste repository to meet long term performance specifications. PMID- 17843488 TI - A global traveling wave on venus. AB - The dominant large-scale pattern in the clouds of Venus has been described as a "gamma" or "Psi" and tentatively identified by earlier workers as a Kelvin wave. A detailed calculation of linear wave modes in the Venus atmosphere verifies this identification. Cloud feedback by infrared heating fluctuations is a plausible excitation mechanism. Modulation of the large-scale pattern by the wave is a possible explanation for the Y. Momentum transfer by the wave could contribute to sustaining the general circulation. PMID- 17843489 TI - Plant defenses. PMID- 17843490 TI - Marine subjects. PMID- 17843491 TI - Some other books of interest. PMID- 17843492 TI - Products & materials. PMID- 17843493 TI - Attacks on Muscle. PMID- 17843494 TI - The Cortical Correlate of Pattern Vision. PMID- 17843495 TI - The Mutagenic Mode of Action of Formalin. PMID- 17843496 TI - Inhibition of Phosphatases by Beryllium and Antagonism of the Inhibition by Manganese. PMID- 17843498 TI - The Action of Penicillin on Bacillus subtilis Growing in the Absence of Amino Acids. PMID- 17843497 TI - The Skin Temperature of an Extremity as a Measure of Its Blood Flow. PMID- 17843499 TI - Free Amino Acids and Peptides in Frog Embryos. PMID- 17843500 TI - A Source of Error in Tracer Experiments with P32. PMID- 17843501 TI - The Interaction of Antimalarials with Nucleic Acids. PMID- 17843502 TI - A Rationale for Plasma Therapy in Poliomyelitis. PMID- 17843503 TI - A Photoelectric Microdensitometer. PMID- 17843505 TI - Trace Minerals in Food Production and Health. PMID- 17843504 TI - Remote Pipetting Apparatus for Dispensing Solutions of Radioisotopes. PMID- 17843506 TI - Meetings & Conferences. PMID- 17843507 TI - History and Development of Chemical Periodicals in the Field of Organic Chemistry: 1877-1949. PMID- 17843508 TI - Fungicidal Properties of Antihistaminics. PMID- 17843509 TI - ASTIA and GSIS. PMID- 17843510 TI - The Occurrence of Branchiostoma (Amphioxus) in Mississippi and Louisiana. PMID- 17843511 TI - Letters to the editor. PMID- 17843512 TI - Letters to the editor. PMID- 17843514 TI - Letters to the editor. PMID- 17843513 TI - World modeling. PMID- 17843515 TI - Test bias. PMID- 17843517 TI - Research management. PMID- 17843516 TI - The college professor. PMID- 17843518 TI - Psychology and health care. PMID- 17843520 TI - Machine translation. PMID- 17843519 TI - Lunar basalts. PMID- 17843521 TI - Who should ultimately own the data? PMID- 17843522 TI - The human nature of human nature. PMID- 17843523 TI - Circumscribed halos. PMID- 17843524 TI - The significance of science. PMID- 17843525 TI - National environmental policy act: how well is it working? PMID- 17843526 TI - NBS Loses Branscomb to IBM. PMID- 17843527 TI - Harvard teaching assistants strike. PMID- 17843528 TI - Court Affirms AEC Authority. PMID- 17843529 TI - OECD: Report Sees Closer Links between Research, Social Objectives. PMID- 17843530 TI - Keeping an Eye on SESPA. PMID- 17843531 TI - Patents: to combine or not to combine. PMID- 17843532 TI - Multivariate analysis of an early hominid metacarpal from swartkrans. AB - Discriminant analysis permits hand bones of living primate genera to be represented as swarms of points in a multidimensional statistical framework within which intergroup relationships, and the affinities of fossil forms, can be examined. The metacarpal of Paranthropus from Swartkrans, South Africa, was so located with respect to groups of monkeys, apes, and modern man. The results suggest that the fossil metacarpal may be functionally similar to that of chimpanzees. PMID- 17843533 TI - Cloud seeding experiments: lack of bias in Florida series. AB - There has been concern about the possibility of selection bias in cloud seeding experiments. Covariates and experimental design have been used to obtain an estimate of this bias. The results indicate that there was no selection bias in the Caribbean and Florida series of cloud seeding experiments. PMID- 17843535 TI - Spacecraft propulsion: new methods. AB - Cosmic plasmas contain energy which may be tapped and used for spacecraft propulsion. The energy needed for launching a spacecraft could be supplied to it from the ground through a plasma channel in the atmosphere. PMID- 17843534 TI - Charge distribution in the light-atom mineral kernite. AB - A charge density analysis of accurate x-ray data for the mineral kernite Na(2)B(4)O(6)(OH)(2). 3H(2)O indicates that the sodium and boron atoms have partial positive charges of 0.4 to 0.5 unit and 0.4 to 0.7 unit, respectively, whereas the oxygen atoms have negative charges of about 0.4 to 0.5 unit. The best agreement with the intensities and with the experimental scale factor is obtained with contracted molecule-optimized atomic orbitals. Difference density maps based on high-order parameters show more density in B-O than in Na-O bonds, thus supporting the covalent nature of the bonds between boron and oxygen atoms. PMID- 17843536 TI - Polyamino acids: preparation from reported proportions of "prebiotic" and extraterrestrial amino acids. AB - Polyamino acids were thermally prepared from the proportions of amino acids identified (sometimes after hydrolysis) among the products of simulated prebiotic syntheses and (after hydrolysis) in lunar and meteoritic samples. Inferences are made concerning the composition of prebiotic protein and the possible extraterrestrial existence of protein-like polymers. PMID- 17843537 TI - Freezing resistance in polar fishes. AB - Arctic and antarctic fishes, living in contact with sea ice at -1.9 degrees C, have plasma equilibrium freezing points near -1.2 degrees C which are dependent on salt concentrations. These supercooled fishes have plasma protein concentrations much higher than other polar animals have, and the proteins impede ice propagation at temperatures down to -2 degrees C. Plasma protein concentration increases as environmental water temperature decreases. PMID- 17843538 TI - Forthcoming events. PMID- 17843539 TI - COMMENT AND CRITICISM. PMID- 17843540 TI - Trowbridge's Physics. PMID- 17843542 TI - The incandescent light on steamers. PMID- 17843541 TI - Rainfall and crops. PMID- 17843543 TI - The voice of serpents. PMID- 17843544 TI - Itinerant science-teachers. PMID- 17843545 TI - The earthquake of Jan. 2. PMID- 17843546 TI - THE DECADENCE OF SCIENCE ABOUT BOSTON. PMID- 17843547 TI - The use of slips in scientific correspondence. PMID- 17843548 TI - THE GEOLOGY OF THE SCOTTISH HIGHLANDS. PMID- 17843549 TI - THE BASIN OF THE CARIBBEAN. PMID- 17843550 TI - THE BALLOON IN METEOROLOGY. PMID- 17843551 TI - A GLANCE AT THE HISTORY OF OUR KNOWLEDGE OF FOSSIL PLANTS. PMID- 17843552 TI - THE KOWAK RIVER. PMID- 17843553 TI - PHYSICAL TRAINING AT AMHERST. PMID- 17843554 TI - SCIENCE AND SURGERY: A TRIUMPHANT RESULT OF EXPERIMENTAL RESEARCH. PMID- 17843555 TI - METEOROLOGICAL NOTES. PMID- 17843557 TI - THE CHEMISTRY AND PHYSICS OF THE SEA. PMID- 17843556 TI - DISCOVERY OF SILURIAN INSECTS. PMID- 17843558 TI - FORCHHEIMER'S TUNNEL-BUILDING IN ENGLAND. PMID- 17843559 TI - SCIENCE NEWS. PMID- 17843560 TI - SCIENCE AND THE SCIENTIFIC ATTITUDE. PMID- 17843561 TI - TECHNOLOGICAL TRENDS AND NATIONAL POLICY. PMID- 17843562 TI - AN OLD ANSWER TO A PRESENT-DAY PROBLEM. PMID- 17843563 TI - THE ANTISCORBUTIC PROPERTIES OF A SALT OF IRON AND ASCORBIC ACID. PMID- 17843564 TI - A COMPANION WORD FOR PLANKTON. PMID- 17843565 TI - THE MAYNARD PLUM--A CARRIER OF THE PEACH MOSAIC VIRUS. PMID- 17843566 TI - A CRYSTALLINE PROTEIN WITH HIGH LACTOGENIC ACTIVITY. PMID- 17843567 TI - THE PROTECTIVE ACTION OF CERTAIN PURINES AGAINST LIVER NECROSIS PRODUCED BY CARBON TETRACHLORIDE AND CHLOROFORM. PMID- 17843568 TI - CORTICO-ADRENAL AND NEURAL EFFECTS ON GONADOTROPIC ACTIVITY OF THE PITUITARY. PMID- 17843569 TI - GLYCYLGLYCINE AS A SEA WATER BUFFER. PMID- 17843570 TI - UNIVERSAL JOINTS FOR SKELETONS. PMID- 17843572 TI - Campus turmoil and problems. PMID- 17843571 TI - Letters to the editor1. PMID- 17843573 TI - Research without Boondoggles. PMID- 17843574 TI - Removing sulfur from coal. PMID- 17843575 TI - Letters to the editor3. PMID- 17843576 TI - Letters to the editor2. PMID- 17843578 TI - Letters to the editor4. PMID- 17843577 TI - Predicting ovulation--precisely. PMID- 17843579 TI - Reproduction in a finite world. PMID- 17843580 TI - The cambodian crisis: reason and emotion. PMID- 17843581 TI - Growth versus the Quality of Life. PMID- 17843582 TI - Batavia: accelerating people as well as particles. PMID- 17843585 TI - Cambodia speech sinks nomination. PMID- 17843584 TI - Campus politics: decentralization is pattern at berkeley, stanford. PMID- 17843586 TI - Domestic Communications Satellites: FCC Still Looking at the Options. PMID- 17843587 TI - Some NIH, NIMH Scientists Lobby To End the War. PMID- 17843588 TI - Tektite glass in apollo 12 sample. AB - The glassy portion of lunar sample 12013 from Apollo 12 is chemically more like some tektites from Java than like any terrestrial igneous rock. It satisfies all the chemical criteria for a tektite. Tektites are relatively recent and acid rocks, whereas the moon is chiefly ancient and basaltic; hence, tektites are probably ejected volcanically, rather than by impact, from the moon. PMID- 17843589 TI - Geological history of the Western north pacific. AB - A considerable portion of the abyssal floor of the western North Pacific was already receiving pelagic sediment in late Jurassic time. Carbonate sediments were later replaced by abyssal clays as the basin deepened and bottom waters became more aggressive. The resulting facies boundary, which can be recognized on seismic profiles, is broadly transgressive; it ranges in age from mid-Cretaceous in the western Pacific to Oligocene in the central Pacific. Cherts are encountered at and below the major facies boundary and appear to have been formed by postdepositional processes. PMID- 17843590 TI - Jupiter: his limb darkening and the magnitude of his internal energy source. AB - The most accurate infrared photometric observations (8 to 14 microns) to date of the average limb darkening of Jupiter have been combined with the most refined deduction of jovian model atmospheres in which flux constancy has been closely maintained in the upper regime of radiative equilibrium and a much more accurate approximation of the 10-and 16-micron vibration-rotation bands of ammonia has been incorporated. The theoretically predicted emergent specific intensity has been multiplied by the spectral response function and folded (mathematically convolved-intersmeared) with the spatial response function of the atmosphere telescope-photometer combination. The resulting comparison indicates that Jupiter is radiating from three to four times as much power as the planet is receiving from the sun. PMID- 17843591 TI - Subliming ice surfaces: freeze-etch electron microscopy. AB - Vacuum sublimation of oriented single crystals of ice at temperatures from -110 to -60 degrees Celsius was studied by electron microscopy with the freeze-etch technique. Sublimation etches the ice surface to produce pits and asperities and above -85 degrees Celsius causes extreme surface roughening. The etch pits are ascribed to surface dislocations, and the extreme roughening is ascribed to the departure from unity of the vaporization coefficient. The asperities could not be attributed to impurities; they may be related to the whiskers that others have observed at higher temperatures. PMID- 17843592 TI - Geochronology: recent development in the lutetium-176/hafnium-176 dating method. AB - The application of the lutetium-176/ hafnium-176 method to gram quantities of minerals containing rare earths is made possible by the development of analytical and isotope dilution techniques for microgram amounts of lutetium and hafnium. The geological redetermination of the half-life of lutetium-176 (3.3 +/- 0.5 x 10(10) years) is in agreement with recent physical measurements. PMID- 17843593 TI - Photochemical oxidants: effect on starch hydrolysis in leaves. AB - Starch-filled leaves of plants which have been subjected to low dosages of naturally occurring photochemical oxidants, ozone, or peroxyacetyl nitrate hydrolyze their starch more slowly when placed in the dark. Delayed hydrolysis occurs irrespective of whether the oxidants were applied during the light or dark period. Occasionally this effect is evident only in the intervenal areas. PMID- 17843594 TI - Antarctic pelecypod faunal peculiarities. PMID- 17843595 TI - Global tectonics. PMID- 17843596 TI - When should the gas guzzler go? PMID- 17843597 TI - Erratum. AB - The price of The Properties of Diamond, J. E. Field, Ed., Academic Press, reviewed by F. P. Bundy (29 Feb., p. 974), is $75. PMID- 17843598 TI - Brown's Administrative Philosophy. PMID- 17843599 TI - Diversion of funds from research. PMID- 17843601 TI - Materials science. PMID- 17843600 TI - Computer models of crystal growth. AB - Dynamic models of crystal surfaces have provided new insights into the crystal growth process. The effects of surface roughening, dislocations, and impurities have been assessed. Certain impurities have been found to cause a larger increase in the growth rate than screw dislocations. PMID- 17843602 TI - Comment on societal risk. AB - There is a need to measure societal risk more accurately; to examine and reevaluate our priorities in risk reduction; to determine the level of expenditure for risk reduction beyond which adverse economic and political effects may be overriding; and to develop a national approach to risk management. PMID- 17843603 TI - Discovery by decree. PMID- 17843604 TI - Rain forests vanishing. PMID- 17843605 TI - Insider's Account of Pollution in U.S.S.R. PMID- 17843606 TI - NSF Finds Slower Growth in Scientific Work Force. PMID- 17843607 TI - MX Missile: A Step Backward for Metric. PMID- 17843608 TI - Commissioner Gilinsky Challenges New NRC Plan. PMID- 17843609 TI - Voyager beguiled by jovian carrousel. PMID- 17843610 TI - The x-rays. PMID- 17843611 TI - Scientific investigation and progress. PMID- 17843613 TI - Plant motility. PMID- 17843612 TI - Conservation in the United States. PMID- 17843614 TI - The growth of fungal hyphae. PMID- 17843615 TI - Hormones in vitro. PMID- 17843616 TI - Basin analysis. PMID- 17843617 TI - Seasonal movements in a salt glacier in iran. AB - The philosophy of the storage of high-grade radioactive wastes in salt seems to be based on the assumption that the salt glaciers of Iran are no longer moving. Monitoring the movements of markers painted onto one of the salt glaciers suggests that the glacier deforms elastically as a result of temperature changes most of the time but flows plastically when it is sufficiently wet during each annual rainy season. PMID- 17843618 TI - Sounding the stratosphere and mesosphere by infrared limb scanning from space. AB - Inversion of the measurements obtained by the infrared limb scanner on the Nimbus 6 satellite has demonstrated that the stratospheric and mesospheric temperatures and ozone concentrations may be obtained remotely from space with accuracy and precision comparable to in situ methods. Such global data have many applications in middle atmospheric research and operational temperature sounding. PMID- 17843619 TI - Corrections in the pioneer venus sounder probe gas chromatographic analysis of the lower venus atmosphere. AB - Misidentification of two peaks from the Pioneer Venus sounder probe gas chromatograph (SPGC), also formerly known as the LGC, gave rise to quantitative errors in the abundances of oxygen, argon, and carbon monoxide. The argon abundance is estimated at 67 parts per million and that of carbon monoxide at 20 parts per million. At this time, no estimates for the oxygen abundance can be made. PMID- 17843620 TI - Enhancement of Superconductivity through Lattice Softening. AB - The superconducting transition temperature of an iridium-yttrium eutectic is enhanced extraordinarily through lattice softening. This is shown by a drastically reduced Debye temperature. PMID- 17843621 TI - Rebound insomnia. PMID- 17843623 TI - A NATIONAL POLICY FOR AGRICULTURAL RESEARCH. PMID- 17843622 TI - PRODUCTS and MATERIALS. PMID- 17843624 TI - THE 1921 EXPEDITION OF THE CALIFORNIA ACADEMY OF SCIENCES TO THE GULF OF CALIFORNIA. PMID- 17843625 TI - APPEAL OF THE AMERICAN CHEMICAL SOCIETY. PMID- 17843626 TI - THE VOTE ON THE EVOLUTION BILL IN THE KENTUCKY STATE LEGISLATURE. PMID- 17843628 TI - PROPOSED LEGISLATION AGAINST THE TEACHING OF EVOLUTION. PMID- 17843627 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17843629 TI - ACOUSTIC TOPOGRAPHY IN A ROOM. PMID- 17843630 TI - MEETINGS OF THE GENETICS SECTIONS. PMID- 17843631 TI - SCIENCE AND THE STATE OF MIND. PMID- 17843632 TI - AN OUTWORN NOMENCLATURAL PRACTICE. PMID- 17843633 TI - ESKIMO SEXUAL FUNCTIONS. PMID- 17843634 TI - SCIENCE IN THE OLD SOUTH. PMID- 17843635 TI - ERYTHROCYTES OF SLOTH. PMID- 17843636 TI - THE TENNESSEE ACADEMY OF SCIENCE. PMID- 17843637 TI - THE INDIANA ACADEMY OF SCIENCE. PMID- 17843638 TI - THE SHAPE OF THE CHICK EMBRYO GROWTH CURVE. PMID- 17843640 TI - NEW OBSERVATIONS ON THE EFFECTS OF CALCIUM DEPRIVATION. PMID- 17843639 TI - THE ROLE OF HEREDITY VERSUS ENVIRONMENT IN LIMB BUD TRANSPLANTS BETWEEN DIFFERENT BREEDS OF FOWL. PMID- 17843641 TI - This week in science. PMID- 17843642 TI - Performance of text retrieval systems. PMID- 17843643 TI - Oak Ridge's Strengths. PMID- 17843644 TI - Desert ants. PMID- 17843645 TI - Performance of text retrieval systems. PMID- 17843647 TI - Corrections and clarifications. AB - In Daniel E. Koshland Jr.'s editorial of 28 April, "Noitall seeks new horizons" (p. 479), it was incorrectly suggested that the world's human population is 4.2 billion. It currently exceeds 5.6 billion. PMID- 17843646 TI - Response. PMID- 17843648 TI - Sciencescope. PMID- 17843649 TI - President's Council Lambastes Ministry. PMID- 17843650 TI - EPA streamlines troubled national ecological survey. PMID- 17843651 TI - Gingrich urges panels to spare science. PMID- 17843652 TI - Leaders pledge more for shrinking pool. PMID- 17843653 TI - Faculty picks up the pieces of shattered research projects. PMID- 17843654 TI - Ocean anomaly triggers record fish kill. PMID- 17843656 TI - NASA Encourages Researchers To Map Search for Alien Earths. PMID- 17843655 TI - Helium-3 crystals captured on video. PMID- 17843658 TI - Chimney in the milky way. PMID- 17843657 TI - Listen Up! The World's Oceans May Be Starting to Warm. PMID- 17843659 TI - Lean and mean contract for argonne. PMID- 17843660 TI - Ecology blooms in santa barbara. PMID- 17843661 TI - Probing Nature's Hairy Secrets. PMID- 17843662 TI - Coupled quantum dots as artificial molecules. PMID- 17843663 TI - The photoreactivity of chlorine dioxide. AB - Determining the detailed photoreactivity of radicals that are of importance in atmospheric processes requires information from both laboratory and field measurements and theoretical calculations. Laboratory experiments and quantum calculations have been used to develop a comprehensive understanding of the photoreactivity of chlorine dioxide (OCIO). The photoreactivity is strongly dependent on the medium (gas phase, liquid solution, or cryogenic matrix). These data reveal details of the complex chemistry of OCIO. The potential role of this radical in stratospheric ozone depletion is discussed in accord with these laboratory measurements. PMID- 17843664 TI - Single molecule electron paramagnetic resonance spectroscopy: hyperfine splitting owing to a single nucleus. AB - Individual pentacene-d(14) molecules doped into a p-terphenyl-d(14) host crystal have been studied by optically detected electron paramagnetic resonance spectroscopy. The magnetic resonance transitions between the triplet sublevels of the pentacene molecule and the splitting of the resonance lines for a molecule that contains a carbon-13 nucleus have been observed in an external magnetic field. This splitting is caused by the hyperfine interaction of the triplet electron spin with the single carbon-13 nuclear spin. PMID- 17843665 TI - Monodisperse metal clusters 10 angstroms in diameter in a polymeric host: the "monomer as solvent' approach. AB - A general methodology is presented for the dispersion of an inorganic compound within an organic polymer host through the use of solubilizing and polymerizable ligands. The dispersion of metal cluster cations 10 angstroms in diameter within a polymer host is achieved by free-radical polymerization of the hexafunctional metal cluster [Mo(6)Cl(8)(NVI)(6)](triflate)(4) with bound polymerizable ligands in N-vinylimidazole (NVI) solutions. Copolymerization of the activated cluster bound ligands with the surrounding medium probably plays a key role in preventing aggregation and produces near monodisperse molecular clusters within the polymer matrix. PMID- 17843666 TI - Ordered metal nanohole arrays made by a two-step replication of honeycomb structures of anodic alumina. AB - A highly ordered metal nanohole array (platinum and gold) was fabricated by a two step replication of the honeycomb structure of anodic porous alumina. Preparation of the negative porous structure of porous alumina followed by the formation of the positive structure with metal resulted in a honeycomb metallic structure. The metal hole array of the film has a uniform, closely packed honeycomb structure approximately 70 nanometers in diameter and from 1 to 3 micrometers thick. Because of its textured surface, the metal hole array of gold showed a notable color change compared with bulk gold. PMID- 17843667 TI - Lehmann discontinuity as the base of an anisotropic layer beneath continents. AB - Long-period surface-wave (R(1), G(1)), body-wave (S, SS, SSS), and ScS reverberation data have been inverted to obtain anisotropic structures along seismic corridors that sample Australia and the western Pacific. These models support the proposal that the Lehmann discontinuity beneath stable continents represents a transition from an anisotropic lithosphere to a more isotropic material in the lower part of the continental tectosphere. PMID- 17843669 TI - Response. PMID- 17843668 TI - Growth of prochlorococcus, a photosynthetic prokaryote, in the equatorial pacific ocean. AB - The cell cycle of Prochlorococcus, a prokaryote that accounts for a sizable fraction of the photosynthetic biomass in the eastern equatorial Pacific, progressed in phase with the daily light cycle. DNA replication occurred in the afternoon and cell division occurred at night. Growth rates were maximal (about one doubling per day) at 30 meters and decreased toward the surface and the bottom of the ocean. Estimated Prochlorococcus production varied between 174 and 498 milligrams of carbon per square meter per day and accounted for 5 to 19 percent of total gross primary production at the equator. Because Prochlorococcus multiplies close to its maximum possible rate, it is probably not severely nutrient-limited in this region of the oceans. PMID- 17843670 TI - Broken bond-bending constraints and glass formation in the oxides. PMID- 17843672 TI - Vignettes: sea changes. PMID- 17843671 TI - Chemical paperwork. PMID- 17843673 TI - Products & materials. PMID- 17843674 TI - TYPES OF VALENCE. PMID- 17843675 TI - PROFESSOR H. BRUCHMANN. PMID- 17843676 TI - THE GEOGRAPHIC DISTRIBUTION OF HYBRIDS. PMID- 17843677 TI - BECHHOLD'S "CAPILLARY PHENOMENON" IN AGRICULTURE. PMID- 17843678 TI - ALBINISM IN THE BLACK BEAR. PMID- 17843680 TI - THE NORTH CAROLINA ACADEMY OF SCIENCE. PMID- 17843679 TI - AN EXPLANATION OF LIESEGANG'S RINGS. PMID- 17843681 TI - OBSERVATIONS OF THE LUNAR ECLIPSE IN CANADA. PMID- 17843682 TI - FLOOD HEALTH MEASURES. PMID- 17843683 TI - THE BACILLUS OF TRACHOMA. PMID- 17843684 TI - LEARNING BY ADULTS. PMID- 17843685 TI - PUBLIC HEALTH AND THE SURVIVAL OF THE FIT. PMID- 17843686 TI - GIPSY MOTH CONTROL. PMID- 17843687 TI - HIGHER ENDEAVOR IN SCIENCE. PMID- 17843688 TI - THE UNIVERSITY AND MEDICAL EDUCATION. PMID- 17843690 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17843689 TI - CARL H. EIGENMANN. PMID- 17843691 TI - THE ARCTIC FLYING OF CAPTAIN WILKINS AND LIEUTENANT EIELSON. PMID- 17843693 TI - EFFECT OF HIGH VOLTAGES ON TANTALUM ANODES. PMID- 17843692 TI - LOSSES IN SPECKLED TROUT FRY AFTER DISTRIBUTION. PMID- 17843694 TI - SURFACE TENSION METHODS. PMID- 17843695 TI - THE NEED FOR DEFINITELY INDICATING NEW SYNONYMY AND NEW COMBINATIONS IN TAXONOMY. PMID- 17843696 TI - THE DECOMPOSITION OF AMMONIA ON IRON CATALYSTS. PMID- 17843697 TI - A CRITICAL FACTOR IN THE EXISTENCE OF SOUTHWESTERN GAME BIRDS. PMID- 17843698 TI - THE WILDLIFE SOCIETY. PMID- 17843699 TI - VITAMINS IN EDIBLE SOYBEANS. PMID- 17843700 TI - HAMILTON PERKINS CADY 1874-1943. PMID- 17843702 TI - PENICILLIN. PMID- 17843701 TI - HAROLD NORRIS ETS. PMID- 17843703 TI - RARE CHEMICALS. PMID- 17843704 TI - THE BIRTH AND DEATH RATES IN GREAT BRITAIN. PMID- 17843705 TI - THE AMERICAN FOUNDATION FOR TROPICAL MEDICINE. PMID- 17843706 TI - A POST-GRADUATE COURSE IN INDUSTRIAL MEDICINE. PMID- 17843707 TI - AIRCRAFT ENGINEERING. PMID- 17843709 TI - GEOLOGY TEXTS FOR LATIN AMERICA. PMID- 17843708 TI - ARBITRARY EDITORIAL CHANGES IN SCIENTIFIC PAPERS. PMID- 17843710 TI - CROWN-GALL BACTERIA. PMID- 17843712 TI - ON THE TYPE OF CHOLINESTERASE PRESENT IN BRAIN TISSUE. PMID- 17843711 TI - COLORED TRANSPARENCIES OF TROPICAL PLANTS. PMID- 17843713 TI - ENTRANCE OF CHLORIDE WITH POTASSIUM INTO LIVE RAT MUSCLE FIBERS--CL-SPACE ERROR. PMID- 17843714 TI - PIGMENT PRODUCTION BY TUBERCLE BACILLUS IN THE PRESENCE OF P-AMINOBENZOIC ACID. PMID- 17843715 TI - GLYOXAL, A NON-IRRITATING ALDEHYDE SUGGESTED AS SUBSTITUTE FOR FORMALIN IN HISTOLOGICAL FIXATIONS. PMID- 17843716 TI - Morality play. PMID- 17843717 TI - Morality play. PMID- 17843718 TI - Morality play. PMID- 17843719 TI - Morality play. PMID- 17843720 TI - Response: morality play. PMID- 17843721 TI - MEETING BRIEFS: Hubble Spectrograph Takes a Hard Look in the Ultraviolet. PMID- 17843722 TI - Sm-Nd Isotopic Data and Earth's Evolution. PMID- 17843724 TI - PROPOSED RUSSIAN GEOLOGICAL SURVEY. PMID- 17843723 TI - Response: Sm-Nd Isotopic Data and Earth's Evolution. PMID- 17843725 TI - EARTHQUAKE WARNINGS. PMID- 17843726 TI - A NEW GERMICIDE. PMID- 17843727 TI - THE ORIGIN OF CLOTHES. PMID- 17843728 TI - SERUM TREATMENT FOR MUSHROOM POISONING. PMID- 17843729 TI - TULAREMIA. PMID- 17843730 TI - THE USES OF TAR AMONG INDIANS. PMID- 17843731 TI - OBJECTIVE AND HUMAN PHYSICS. PMID- 17843732 TI - LOUIS AGASSIZ FUERTES. PMID- 17843733 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17843734 TI - A COMMUNICATION ON THE MAGNETO-OPTICAL EFFECT AND A CORRECTION. PMID- 17843735 TI - THE EUROPEAN LARCH CANKER IN AMERICA. PMID- 17843736 TI - "WASHBOARD" OR "CORDUROY" EFFECT DUE TO THE TRAVEL OF AUTOMOBILES OVER DIRT ROADS. PMID- 17843738 TI - THE SEARCH FOR ELEMENTS ESSENTIAL IN ONLY SMALL AMOUNTS FOR PLANT GROWTH. PMID- 17843737 TI - THE DEFICIENCY OF ENGLISH UNITS OF MEASURE AND WEIGHT FOR SCIENTIFIC AND TECHNICAL USES. PMID- 17843739 TI - DECALCIFICATION OF BONE IN ACID FREE SOLUTIONS. PMID- 17843741 TI - E.M.F. INDUCED IN A STRAIGHT WIRE BY A CURRENT IN A PARALLEL STRAIGHT CONDUCTOR. PMID- 17843740 TI - A CONTAINER FOR FIELD COLLECTION OF MOSQUITO LARVAE. PMID- 17843742 TI - RATE OF VIRUS SPREAD IN TOMATO PLANTS. PMID- 17843744 TI - SOUTHWESTERN ARCHEOLOGICAL CONFERENCE. PMID- 17843743 TI - FEEDING PLANTS MANGANESE THROUGH THE STOMATA. PMID- 17843745 TI - FINANCIAL GRANTS TO ADVANCE RESEARCH. PMID- 17843746 TI - Growth Rate of Industrial Research. PMID- 17843747 TI - Lamont Natural Radiocarbon Measurements, I. PMID- 17843748 TI - Fissidens pauperculus Howe and Orthodontium gracile Bruch & Schimper: Mosses Associated with the Coast Redwood Forest. PMID- 17843749 TI - Statement on Peyote. PMID- 17843750 TI - The shipment of carcinogens. PMID- 17843751 TI - Letter to the editor. PMID- 17843752 TI - A private experiment. PMID- 17843753 TI - Responsibility. PMID- 17843754 TI - Letter to the editor. PMID- 17843755 TI - Politics and engineers. PMID- 17843756 TI - Technological initiatives and political realities. PMID- 17843757 TI - Upper Pleistocene Radiocarbon-Dated Artefacts from the Northern Yukon: Man was in Beringia 27,000 years ago. AB - The evidence presented here indicates that man lived in the eastern part of the Beringian refugium before the peak of the late Wisconsin glaciation (27). He had sharp, stone tools intended for working bone and means of breaking large mammoth bones. Probably he hunted mammoth and caribou, and prepared the skins of the caribou for use as clothing and perhaps shelter. It is possible that he migrated to southern North America, although evidence for the presence of man there prior to the peak of the Wisconsin glaciation is at present in dispute (28). We do not know whether his culture should be classified as Mousteroid or Aurignacoid in Muller-Beck's scheme (23), whose criteria are taken from stone implements of which we have none, although we infer their presence. Our data suggest that in Beringia, and therefore probably in Siberia and the Far East, the transition from Middle Paleolithic to Upper Paleolithic levels of technology occurred at a relatively early date. This raises the larger question: Did the transition from Middle to Upper Paleolithic occur simultaneously in many parts of the world, or did it begin in and spread from one area (23)? PMID- 17843758 TI - NIH Training Grants: Going, Going, Gone? PMID- 17843759 TI - Earl L. Butz, Counselor for Natural Resources: President's Choice a Surprise for Environmentalists. PMID- 17843760 TI - Nuclear Safety: AEC Report Makes the Best of It. PMID- 17843761 TI - Moss heads senate space panel. PMID- 17843762 TI - Alcoholism: On-the-Job Referrals Mean Early Detection, Treatment. PMID- 17843763 TI - Photorespiration: key to increasing plant productivity? PMID- 17843764 TI - Overbank Sedimentation in the Delaware River Valley during the Last 6000 Years. AB - A thick sequence of floodplain sediments has accumulated in the Delaware River Valley by the process of overbank deposition. Textures in the sediments indicate that the sequence contains no point-bar deposits and is unbroken by periods of erosion. Fourteen radiocarbon dates show that deposition began at least 6000 years ago and has continued to the present. Because the Delaware River shifts its position laterally at a very slow rate, overbank deposition becomes dominant in the construction of its floodplain. PMID- 17843765 TI - Magnetic transitions observed in sulfide minerals at elevated pressures and their geophysical significance. AB - The magnetic behavior of iron in chalcopyrite (CuFeS(2)) and pyrrhotite (Fe(7)S(8)) in the pressure range from 1 atmosphere to 20 kilobars has been studied by Mossbauer spectroscopy. Both chalcopyrite and pyrrhotite exhibit transitions from magnetically ordered to disordered states over the range from 5 to 16 kilobars. Both transitions, particularly the loss of ferrimagnetism in pyrrhotite, have geophysical consequences. PMID- 17843766 TI - Red sea drillings. AB - Recent drilling in the Red Sea has shown that much of the basin is underlain by evaporites of a similar age to that of evaporites found in the Mediterranean Sea. These evaporites and their structural positions indicate that other brine areas are present-and, indeed, several others have been discovered. PMID- 17843767 TI - Caste-specific compounds in male carpenter ants. AB - Three caste-specific substances new to arthropod glandular secretions occur in the mandibular glands of male ants of five species in the genus Camponotus. These volatile compounds, which are not found in alate females or workers, have been identified as methyl 6-methyl salicylate, 2,4-dimethyl-2-hexenoic acid, and methyl anthranilate. The free acid has not been described previously. PMID- 17843769 TI - This week in science. PMID- 17843768 TI - Isolation and structure determination of blepharismin, a conjugation initiating gamone in the ciliate blepharisma. AB - One of the gamones (gamone II) which are effective for the induction of conjugation in Blepharisma intermedium has been isolated in a crystalline form and designated as blepharismin. From the result of chemical and spectroscopic investigations, in which x-ray crystallographic analysis was used as a definitive tool, blepharismin has been found to have the structure of calcium 3-(2' formylamino-5'-hydroxybenzoyl)lactate. PMID- 17843770 TI - Support for materials science and engineering. PMID- 17843771 TI - Punitive damages and innovation. PMID- 17843772 TI - In reply: u.s. Oil and gas consumption: is another crisis ahead? PMID- 17843773 TI - U.s. Oil and gas consumption: is another crisis ahead? PMID- 17843774 TI - Erratum. AB - The first sentence of the caption for the figure on page 525 accompanying Marcia Barinaga's Research News artide "Neuroscience models the brain" (2 Feb., p. 524) should have read, "Computer simulation by Kenneth D. Miller models formation of ocular dominance columns." The photo credit fbr the figure should have been to Kenneth D. Miller. PMID- 17843776 TI - In reply: punitive damages and innovation. PMID- 17843775 TI - In reply: punitive damages and innovation. PMID- 17843778 TI - With a little help. . . PMID- 17843777 TI - In reply: punitive damages and innovation. PMID- 17843779 TI - SDI Heads for Fiscal Crash: While the number of tests is going up, the budget is going down, and the rationale is changing. PMID- 17843780 TI - Army, Air Force Eye SDI Spinoffs. PMID- 17843781 TI - The ups and downs of strategic defense weapons. PMID- 17843782 TI - In Peru, Even Potato Research Is High Risk: Dodging guerrilla attacks and inflation that runs at 2000% a year, researchers high in the Andes are improving the potato. PMID- 17843784 TI - Academy of engineering elects new members. PMID- 17843783 TI - Greenpeace and Science: Oil and Water?: Greenpeace U.K. has hired a director of science and begun an ambitious program of funding scientific research, raising questions about what role advocacy groups should play in science. PMID- 17843785 TI - Particle physicists look to the heavens. PMID- 17843786 TI - Tweaking molecules with laser light. PMID- 17843787 TI - Ozone destruction closer to home. PMID- 17843788 TI - Stanford patents pay. PMID- 17843789 TI - Technology unlocks "lost" writings. PMID- 17843790 TI - Transgenic carp: pond-ready? PMID- 17843791 TI - Prospectors Cash In on Geologist's Find. PMID- 17843792 TI - Deep magma body beneath the summit and rift zones of kilauea volcano, hawaii. AB - A magnitude 7.2 earthquake in 1975 caused the south flank of Kilauea Volcano, Hawaii, to move seaward in response to slippage along a deep fault. Since then, a large part of the volcano's edifice has been adjusting to this perturbation. The summit of Kilauea extended at a rate of 0.26 meter per year until 1983, the south flank uplifted more than 0.5 meter, and the axes of both the volcano's rift zones extended and subsided; the summit continues to subside. These ground-surface motions have been remarkably steady and much more widespread than those caused by either recurrent inflation and deflation of the summit magma chamber or the episodic propagation of dikes into the rift zones. Kilauea's magmatic system is, therefore, probably deeper and more extensive than previously thought; the summit and both rift zones may be underlain by a thick, near vertical dike-like magma system at a depth of 3 to 9 kilometers. PMID- 17843793 TI - Femtosecond pulse sequences used for optical manipulation of molecular motion. AB - Optical control over elementary molecular motion is enhanced with timed sequences of femtosecond (10(-15) second) pulses produced by pulse-shaping techniques. Appropriately timed pulse sequences are used to repetitively drive selected vibrations of a crystal lattice, in a manner analogous to repetitively pushing a child on a swing with appropriate timing to build up a large oscillation amplitude. This process corresponds to repetitively "pushing" molecules along selected paths in the lattice. Amplification of selected vibrational modes and discrimination against other modes are demonstrated. Prospects for more extensive manipulation of molecular and collective behavior and structure are clearly indicated. PMID- 17843794 TI - The Framework Topology of ZSM-18, a Novel Zeolite Containing Rings of Three (Si,Al)-O Species. AB - ZSM-18 is the first known aluminosilicate zeolite to contain rings of three (Si,Al)-O species (3-rings). Its framework topology has been determined by hypothetical model building, subsequent constrained distance and angle least squares refinements of atomic coordinates, and x-ray powder diffraction pattern simulations. Its channel structure is characterized by a linear unidimensional 12 ring channel, with an approximate pore opening of 7.0 angstroms. In addition, the channels are lined with pockets that are capped by 7-rings with dimensions of 2.8 angstroms by 3.5 angstroms. An intraframework packing model of the organic moiety used in the synthesis suggests that a strong templating effect may be responsible for the formation of this unusual zeolite structure. PMID- 17843795 TI - Amazon deforestation and climate change. AB - A coupled numerical model of the global atmosphere and biosphere has been used to assess the effects of Amazon deforestation on the regional and global climate. When the tropical forests in the model were replaced by degraded grass (pasture), there was a significant increase in surface temperature and a decrease in evapotranspiration and precipitation over Amazonia. In the simulation, the length of the dry season also increased; such an increase could make reestablishment of the tropical forests after massive deforestation particularly difficult. PMID- 17843796 TI - Fossil soils and grasses of a middle miocene East african grassland. AB - Fossil soils and grasses from the well-known Miocene mammal locality of Fort Ternan, southwestern Kenya, are evidence of a mosaic of grassy woodland and wooded grassland some 14 million years ago. This most ancient wooded grassland yet known on the African continent supported more abundant and diverse antelopes than known earlier in Africa. Ape fossils at Fort Ternan, including Kenyapithecus wickeri, were associated with woodland parts of the vegetation mosaic revealed by paleosols. Grassland habitats were available in East Africa long before the evolutionary divergence of apes and humans some 5 to 10 million years ago. PMID- 17843797 TI - Imaging and manipulating molecules on a zeolite surface with an atomic force microscope. AB - The adsorption of neutral molecules and ions on the surfaces of zeolites was observed in real time with an atomic force microscope (AFM). Direct imaging of the surface of the zeolite clinoptilolite was possible by using a diluted tert butyl ammonium chloride solution as a medium. Images of the crystal in different liquids revealed that molecules could be bound to the surface in different ways; neutral molecules of tert-butanol formed an ordered array, whereas tert-butyl ammonium ions formed clusters. These absorbed molecules were not rearranged by the AFM tip when used in an imaging mode. However, when a sufficiently large force was applied, the tip of the AFM could rearrange the tert-butyl ammonium ions on the zeolite surface. This demonstration of molecular manipulation suggests new applications, including biosensors and lithography. PMID- 17843799 TI - Complex Organismal Functions. Integration and Evolution in Vertebrates. D. B. Wake and G. Roth, Eds. Wiley-Interscience, New York, 1989. xiv, 451 pp., illus. $122. Life Sciences Research Reports, vol. 45. From a workshop, Berlin, F.R.G., Aug.-Sept. 1988. PMID- 17843800 TI - Prediction of Protein Structure and the Principles of Protein Conformation. Gerald D. Fasman, Ed. Plenum, New York, 1989. xiv, 798 pp., illus. $95. PMID- 17843801 TI - Large Deviations. Jean-Dominique Deuschel and Daniel W. Stroock. Academic Press, San Diego, CA, 1989. xiv, 307 pp. $34.95. Pure and Applied Mathematics, vol. 137. PMID- 17843802 TI - Products & materials. PMID- 17843803 TI - THE TOBACCO-PLANT. PMID- 17843804 TI - A STEEL PRESSURE-BLOWER. PMID- 17843805 TI - WHAT STANLEY HAS DONE FOR THE MAP OF AFRICA. PMID- 17843806 TI - USEFUL PLANTS IN GUATEMALA. PMID- 17843807 TI - PHTHISIS IN HIGH ALTITUDES. PMID- 17843808 TI - LEPROSY HERE AND ELSEWHERE. PMID- 17843809 TI - TOLERANCE OF OPERATIONS ON THE LIVER. PMID- 17843810 TI - THE "NORMAL" DIET. PMID- 17843811 TI - HEALTH MATTERS. PMID- 17843812 TI - THE FISKE RANGE-FINDER. PMID- 17843813 TI - Physical Fields. PMID- 17843814 TI - Musical Flames. PMID- 17843815 TI - Mocking-Birds' Phrases. PMID- 17843816 TI - The Orthography of "Alleghany". PMID- 17843817 TI - Erratum. AB - In the report "Monoclonal antibodies in the lymphatics: Selective delivery to lymph node metastases of a solid tumor" by J. N. Weinstein et al. (28 Oct., p. 423), figure 2 was printed incorrectly. In the bar graph on the left, the captions under N = 13 and N = 4 were interchanged. The correct figure is printed below. [see figure source pdf.]. PMID- 17843818 TI - Personal computing in education and research. PMID- 17843820 TI - Clinch River Dies: But the breeder R & D program lives on with $300 million to spend this year; the big question is who will pay to close Clinch River? PMID- 17843819 TI - A paleozoic pangaea. AB - Paleozoic paleogeographies should be consistent with all available, reliable data. However, comparison of three different Devonian paleogeographies that are based largely or wholly on the data of remanent magnetism show them to be inconsistent in many regards. When these three paleogeographies are provided with possible ocean surface current circulation patterns, and have added to them lithofacies and biogeographic data, they also are shown to be inconsistent with such data. A pangaeic reconstruction positioned in the Southern Hemisphere permits the lithofacies and biogeographical data to be reconciled in a plausible manner. PMID- 17843821 TI - Next on the firing line? PMID- 17843822 TI - Pork barrel funding deemed not kosher. PMID- 17843823 TI - World model for the joint chiefs. PMID- 17843824 TI - Apes and AIDS. PMID- 17843825 TI - Kroc foundation dissolved. PMID- 17843826 TI - NSF Maps Program in Science Education. PMID- 17843827 TI - Scientists endorse ban on antibiotics in feeds. PMID- 17843828 TI - Hospices compared with conventional care. PMID- 17843829 TI - Isotopes Add Support for Asteroid Impact: Osmium isotope analysis supports an asteroid impact 65 million years ago but cannot exclude a huge volcanic eruption. PMID- 17843830 TI - Number of Organic Superconductors Grows: New discoveries suggest that the superconductivity of certain organic salts is a general phenomena. PMID- 17843831 TI - Australian archeology: a prehistory of australia, new Guinea and sahul. PMID- 17843832 TI - Classic ore deposits: precambrian sulphide deposits. PMID- 17843833 TI - Lizards: lizard ecology. PMID- 17843835 TI - Ungulate behavior: gazelles and their relatives. PMID- 17843834 TI - Neuromuscular physiology: muscles and their neural control. PMID- 17843836 TI - Osmium-187/osmium-186 in manganese nodules and the cretaceous-tertiary boundary. AB - As a result of the radioactive decay of rhenium-187 (4.6 x 10(10) years) the osmium-187/osmium-186 ratio changes in planetary systems as a function of time and the rhenium-187/osmium-186 ratio. For a value of the rhenium-187/osmium-186 ratio of about 3.2, typical of meteorites and the earth's mantle, the present-day osmium-187/osmium-186 ratio is about 1. The earth's continental crust has an estimated rhenium-187/osmium-186 ratio of about 400, so that for a mean age of the continent of 2 x 10(9) years, a present-day osmium-187/osmium-186 ratio of about 10 is expected. Marine manganese nodules show values (6 to 8.4) compatible with this expectation if allowance for a 25 percent mantle osmium supply to the oceans is allowed. The Cretaceous-Tertiary boundary iridium-rich layer in the marine section at Stevns Klint, Denmark, yields an osmium-187/osmium-186 ratio of 1.65, and the one in a continental section in the Raton Basin, Colorado, is 1.29. The simplest explanation is that these represent osmium imprints of predominantly meteoritic origin. PMID- 17843837 TI - Computer simulations of the belousov-zhabotinsky reaction. AB - Morphological features of the two-dimensional Belousov-Zhabotinsky reaction were modeled with an algorithm involving only two simple parameters, one describing the productivity of the reaction on a local scale length and the other characterizing the delay or quiescent time after the localized reaction. Self organizing wavelike structures, including single-and multiarmed spirals, were most easily generated. PMID- 17843838 TI - Phaeodarian skeletons: their role in silica transport to the deep sea. AB - The skeletons of phaeodarian Radiolaria transport and redistribute silica to the tropical deep oceans by dissolving in the water column and on the sea floor. The skeletons are initially solid but within a few days to months become progressively more porous while settling through the water column. Phaeodarian Radiolaria are rarely preserved in the bottom sediments; in contrast, polycystine Radiolaria are the dominant Radiolaria preserved in the fossil record. This preservational difference may be due to differences in skeletal constituents. PMID- 17843839 TI - Seep oil and gas in gulf of Mexico slope sediment. AB - Concentrations in Gulf of Mexico slope sediment of material soluble in methanol and benzene as high as 4.5 percent are shown to be attributable to biodegraded petroleum. Associated carbonate deposits and organic sulfur are the products of the microbial oxidation of petroleum and sulfate reduction. The results of chemical and carbon isotope analyses indicate that high concentrations of hydrocarbon gases, from methane to pentane, are petroleum rather than microbiologically derived. These hydrocarbons, believed to have been produced thermally at depth, probably reached the surface through faults and fractures associated with salt diapirs. PMID- 17843840 TI - Nickel: an essential micronutrient for legumes and possibly all higher plants. AB - Soybean plants deprived of nickel accumulated toxic concentrations of urea (2.5 percent) in necrotic lesions on their leaflet tips. This occurred regardless of whether the plants were supplied with inorganic nitrogen or were dependent on nitrogen fixation. Nickel deprivation resulted in delayed nodulation and in a reduction of early growth. Addition of nickel (1 microgram per liter) to the nutrient media prevented urea accumulation, necrosis, and growth reductions. This evidence suggests that nickel is essential for soybeans and possibly for higher plants in general. PMID- 17843841 TI - A morphogenetically competent soybean suspension culture. AB - A morphogenetically competent suspension culture was derived from embryonic axes of Glycine max cv. Mitchell. The cultural history included visual selection for nonfriable, embryo-like structures, recurrent selection in a regime of 2,4 dichlorophenoxyacetic acid exposure and withdrawal, and the replacement of the nitrogen in a Murashige and Skoog salts-based medium with 20 millimolar ammonium citrate. The embryoids produced by this suspension are capable of completing plantlet development. The suspension can be maintained by serial subculture. PMID- 17843842 TI - Nocturnal aerial predation of fireflies by light-seeking fireflies. AB - Female Photuris fireflies guided by their prey's luminescence attack flying fireflies at night. They sometimes use this hunting tactic together with prey attraction by mating-signal mimicry. Such predation could have been a major factor in the evolution of signaling behavior of American fireflies. Nocturnal aerial predation by an insect and attack guidance on energy emitted by airborne prey have not previously been reported. PMID- 17843843 TI - SCIENCE NEWS. PMID- 17843844 TI - THE FAD AS A FACTOR IN BOTANICAL PUBLICATION. PMID- 17843845 TI - OBITUARY. PMID- 17843847 TI - READING KNOWLEDGE. PMID- 17843846 TI - MISNAMED CULTURES AND STUDIES OF THE TUBERCLE BACILLUS. PMID- 17843848 TI - A METHOD FOR THE DISARTICULATION OF SKULL BONES. PMID- 17843849 TI - RECENT FIND OF MAMMOTH REMAINS IN THE QUATERNARY OF FLORIDA, TOGETHER WITH ARROWHEAD. PMID- 17843850 TI - A NOTE ON THE DETERMINATION OF IRON IN BLOOD AND BIOLOGICAL FLUIDS. PMID- 17843851 TI - DISCARDED ROENTGEN RAY FILM FOR THE MOUNTING OF MUSEUM SPECIMENS. PMID- 17843852 TI - THE INACTIVATION OF MOSAIC DISEASE VIRUS BY PULVERIZING INFECTED TISSUE. PMID- 17843853 TI - STUDIES ON THE ETIOLOGY OF POLIOMYELITIS: ISOLATION AND CULTIVATION OF AN ORGANISM AND TRANSMISSION OF THE DISEASE IN MONKEYS. PMID- 17843854 TI - THE RELATIONSHIP BETWEEN THE WATER CONTENT AND OXYGEN CONSUMPTION OF THE ORGANISM. PMID- 17843855 TI - SCIENCE NEWS. PMID- 17843856 TI - AN ANTHROPOLOGIST LOOKS AT MEDICINE. PMID- 17843857 TI - BEHAVIOR OF THYROID FOLLICLES IN THE HARVEY-LOOMIS CENTRIFUGE MICROSCOPE. PMID- 17843858 TI - ORIGIN OF THE SOUTHERN APPALACHIAN GRASS BALDS. PMID- 17843859 TI - MIGRATION OF GRAY SQUIRRELS. PMID- 17843860 TI - EFFECTS OF ETHYLENE ON THE PLANT GROWTH HORMONE. PMID- 17843861 TI - DISPOSAL OF PAPERS. PMID- 17843862 TI - THE INVASION OF THE BODY BY ANIMAL POISONS. PMID- 17843863 TI - SEXUAL PHASES IN THE QUOHOG. PMID- 17843864 TI - MOUNTING MEDIUM FOR CLEARED SPECIMENS. PMID- 17843865 TI - GYROSCOPES AND TOPS WITH BALL BEARINGS. PMID- 17843866 TI - APPLICATION OF THE PRINCIPLE OF THE ROSIWAL PETROGRAPHIC ANALYSIS TO GEOGRAPHIC RECONNAISSANCE. PMID- 17843868 TI - Space Science: The future holds exciting possibilities for scientific research by man in space. PMID- 17843867 TI - Biologists' Choice. PMID- 17843869 TI - Defense Secretary McNamara Says Strength Now Gives U.S. Chance To Cut Arms Race Costs and Perils. PMID- 17843870 TI - Education: President's Program Provides More Room at Top. PMID- 17843871 TI - Postscript to Portland's Penguins. PMID- 17843872 TI - Population: National Academy Group Nearing Completion of Study. PMID- 17843873 TI - A Stonefly Aquatic in the Adult Stage. AB - An undescribed species of stonefly (Plecoptera) of the genus Capnia, taken in Lake Tahoe, California and Nevada, appears to pass its entire life history at depths of nearly 200 to at least 264 feet. PMID- 17843874 TI - Callosal Section: Its Effect on Performance of a Bimanual Skill. AB - Four out of five monkeys showed no lessening of the ability to perform a motor habit requiring concurrent movement of the two hands in opposite directions when the callosum was cut after training. However, in only one animal was there significant transfer, between the hands, of a shape-discrimination habit learned postoperatively. PMID- 17843875 TI - Thermal Properties of Meteoritic Iron from -150{degrees} to 300{degrees} Celsius. AB - Thermal diffusivity and specific heat have been measured by the flash method on a small specimen of meteoritic iron from the Canyon Diablo fall. Measurements have been made over the temperature range -150 degrees to 300 degrees C from which thermal conductivity values have been calculated. PMID- 17843876 TI - Polymer Structure: Cross-Linking of a Polybenzimidazole. AB - The torsional braid technique was used to monitor the changes in rigidity and damping characteristics of a polybenzimidazole as it changes from a thermoplastic polymer to a thermoset resin at about 450 degrees C. In an intermediate process the thermoplastic backbone of the polymer becomes flexible. PMID- 17843877 TI - Heritability of Variations in Oil Content of Individual Corn Kernels. AB - Nuclear magnetic resonance spectroscopy was used to determine oil content of individual corn kernels in order to evaluate this technique as an aid in the development of strains having greater oil content. This method is rapid and does not impair viability. Individual kernels from a selfed single-cross ear ranged from 2.7 to 5.4 percent oil and were significantly correlated (r = +0.75) with the oil content of their progeny ears. This indicates that the single-kernel differences in oil content were heritable, and this method may greatly increase selection efficiency in breeding for higher oil content in corn. PMID- 17843878 TI - Virus-Containing Leukocytes in Polioencephalitis. AB - Crystalline aggregates of strain MM virus occur in polymorphonuclear leukocytes in association with osmiophilic granular structures which are occasionally membrane-bound. This suggests either a phagocytosis and segregation of virus by leukocytes, analogous to the disposition of bacteria by leukocytes, or a utilization of the leukocyte by the virus as a host cell for virus replication. PMID- 17843879 TI - Predictors of Human Food Consumption. AB - Efficient psychological and nutritional measures by which food acceptance can be predicted were sought. Three-fourths of the variation in percentage of enlisted military personnel who take the foods at the serving table is predictable from knowledge of food preferences, the subjective satiety or "fillingness" of the food, and the amount of two major nutrients, fat and protein, the food contains. PMID- 17843880 TI - Xenon Hydroxide: An Experimental Hazard. PMID- 17843881 TI - SOME DEVELOPMENTS IN THE CHEMICAL INDUSTRIES AS A RESULT OF WAR CONDITIONS. PMID- 17843883 TI - SPECTROSCOPIC INVESTIGATION. PMID- 17843882 TI - THE NEW HOPKINS MARINE STATION OF STANFORD UNIVERSITY. PMID- 17843884 TI - AREAS OF AUDIBILITY. PMID- 17843885 TI - THE DESICCATION OF THE EARTH. PMID- 17843886 TI - PRIMITIVE KNOWLEDGE OF INOCULATION. PMID- 17843887 TI - THE ANNUAL MEETING OF THE NATIONAL ACADEMY OF SCIENCES. PMID- 17843888 TI - A SIMPLE METHOD OF MEASURING PHOTOSYNTHESIS. PMID- 17843889 TI - SOME NEW JERSEY ESKERS. PMID- 17843890 TI - COLORATION OF THE RUFFED GROUSE. PMID- 17843891 TI - VOLCANIC ROCKS IN THE KEEWATIN OF MINNESOTA. PMID- 17843893 TI - CURRENT NOTES ON ANTHROPOLOGY.--XXXVII. PMID- 17843892 TI - SECRET LANGUAGE OF CHILDREN. PMID- 17843894 TI - WERNER'S REAL CONTRIBUTION TO GEOLOGY. PMID- 17843895 TI - HABITS OF THE PURPLE FINCH--CORPODACUS PURPUREUS, GRAY. PMID- 17843896 TI - JEWS AND HITTITES. PMID- 17843897 TI - THE AGE OF THE IRON ORES OF EAST TEXAS. PMID- 17843898 TI - THE DEPARTMENTS OF GEOGRAPHY. PMID- 17843899 TI - SORGHUM SUGAR. PMID- 17843900 TI - THE CHEMIST IN THREE WARS. PMID- 17843902 TI - THE VAUGHAN RESEARCH AWARDS IN HORTICULTURE. PMID- 17843901 TI - MICROFILM RECORDS OF THE LINNEAN SOCIETY OF LONDON. PMID- 17843903 TI - POSTGRADUATE COURSE IN INDUSTRIAL MEDICINE AT THE LONG ISLAND COLLEGE OF MEDICINE. PMID- 17843904 TI - THE FIFTIETH ANNIVERSARY OF THE DEPARTMENT OF ZOOLOGY OF COLUMBIA UNIVERSITY. PMID- 17843905 TI - NEW EPIDEMIOLOGICAL ASPECT OF SPOTTED FEVER IN THE GULF COAST OF TEXAS. PMID- 17843906 TI - THE OCCURRENCE AND SIGNIFICANCE OF MARINE CELLULOSE-DESTROYING FUNGI. PMID- 17843908 TI - THE DIFFUSION OF SCIENCE. PMID- 17843907 TI - ADDITIONAL STEROIDS WITH LUTEOID ACTIVITY. PMID- 17843910 TI - THE FOOD-PRODUCING POWER OF GREAT BRITAIN. PMID- 17843909 TI - TOO HOT FOR THE DINOSAUR. PMID- 17843911 TI - THE ABSORPTION AND DISTRIBUTION OF INSULIN LABELLED WITH RADIOACTIVE IODINE. PMID- 17843912 TI - COLCHICINE INDUCED UNIVALENTS IN DIPLOID ANTIRRHINUM MAJUS L. PMID- 17843913 TI - CRYSTALLIZATION OF A PROTEIN FROM POLIOMYELITIS INFECTED MOUSE BRAIN. PMID- 17843914 TI - ON A NEW PROTEASE FROM PILEUS MEXICANUS. PMID- 17843915 TI - FUNGICIDAL VALUE OF THE SALICYLATES. PMID- 17843916 TI - SCIENCE NEWS. PMID- 17843917 TI - THE SCIENTIFIC BACKGROUND OF THE FOREST POLICY OF THE UNITED STATES. PMID- 17843918 TI - LUTHER EMMETT HOLT. PMID- 17843920 TI - THE CARDIO-INHIBITORY CENTER. PMID- 17843919 TI - THE SPRING MEETING OF THE EXECUTIVE COMMITTEE. PMID- 17843922 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17843921 TI - DALTON AS A NAME FOR THE UNIT OF ATOMIC WEIGHT. PMID- 17843923 TI - THE INFLUENCE ON FISHERIES OF THE WAR. PMID- 17843924 TI - SELF-FERTILIZATION IN NICOTIANA. PMID- 17843925 TI - THE ORIENTED WEDGE THEORY OF EMULSIONS AND THE INVERSION OF EMULSIONS. PMID- 17843926 TI - THE MICHIGAN ACADEMY OF SCIENCE, ARTS AND LETTERS. PMID- 17843927 TI - THE OHIO ACADEMY OF SCIENCE. PMID- 17843928 TI - THE UTAH ACADEMY OF SCIENCES. PMID- 17843929 TI - THE DESTRUCTION OF WILD ANIMALS. PMID- 17843930 TI - THE RESOURCES OF THE PACIFIC OCEAN. PMID- 17843931 TI - TREATMENT OF LUPUS. PMID- 17843933 TI - PLANETS IN JULY. PMID- 17843932 TI - THE ELECTRIC NEEDLE IN SURGERY. PMID- 17843934 TI - THE EARTHQUAKE OF JULY 7. PMID- 17843935 TI - PROPAGANDA BASED ON PSYCHOLOGY. PMID- 17843936 TI - THE FARADAY BENZENE CENTENARY. PMID- 17843938 TI - ASA GRAY. PMID- 17843937 TI - EVOLUTION AND EDUCATION IN THE TENNESSEE TRIAL. PMID- 17843939 TI - THE DEMONSTRATION OF NEPHROSTOMES IN THE EARTHWORM. PMID- 17843941 TI - PROFESSOR O. C. MARSH AND PITHECANTHROPUS. PMID- 17843940 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17843942 TI - FAUNA HAWAIIENSIS. PMID- 17843943 TI - COMPENSATING THE UNEMPLOYED EYE IN MONOCULAR INSTRUMENTS. PMID- 17843944 TI - DISEASES OF THE RUFFED GROUSE. PMID- 17843945 TI - A BACTERIOLOGICAL NOTE RELATIVE TO THE FRANKLIN ARCTIC RELIEF EXPEDITION OF 1848. PMID- 17843946 TI - THE MICHIGAN ACADEMY OF SCIENCE, ARTS AND LETTERS. PMID- 17843947 TI - THE OHIO ACADEMY OF SCIENCE. PMID- 17843949 TI - SCIENCE NEWS. PMID- 17843948 TI - THE INDIANA ACADEMY OF SCIENCES. PMID- 17843950 TI - ENTOMOLOGY. PMID- 17843951 TI - UNVERIFIED GEOGRAPHIC RANGES. PMID- 17843952 TI - PLINY EARLE GODDARD. PMID- 17843953 TI - AN X-RAY EXAMINATION OF THE ANHYDROUS Na2SO4-Al2(SO4)3 SYSTEM. PMID- 17843954 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17843955 TI - MAINTAINING THE STANDARD AND THE SCIENTIFIC USEFULNESS OF THE NATIONAL PARKS. PMID- 17843956 TI - ANTS AS PROSPECTORS. PMID- 17843957 TI - A SUBSTITUTE FOR "BELIEVE". PMID- 17843958 TI - DICTION IN SCIENTIFIC WRITINGS. PMID- 17843959 TI - ETHYLENE GLYCOL AS AN ATMOMETER REAGENT TO MEASURE THE EVAPORATING ENVIRONMENT AT TEMPERATURES BELOW FREEZING. PMID- 17843960 TI - THE CELL SAP OF VALONIA AND HALICYSTIS. AB - Comparison is made between the saps of Valonia ventricosa of Florida and the Bermuda Halicystis, formerly known as V. ventricosa. An even higher percentage of potassium is found in V. ventricosa than in V. macrophysa, while Halicystis has been shown to have very little. PMID- 17843962 TI - SCIENCE NEWS. PMID- 17843961 TI - THE PROBABLE AMOUNT OF ULTRA-VIO- LET RADIATION OBTAINED INDOORS THROUGH ULTRA VIOLET TRANSMITTING GLASS. PMID- 17843963 TI - SCIENTIFIC APPROACHES TO THE STUDY OF THE HUMAN MIND. PMID- 17843965 TI - FACETTED PEBBLES IN EASTERN VENEZUELA. PMID- 17843964 TI - THE AMERICAN MATHEMATICAL SOCIETY 1888-1938. PMID- 17843966 TI - ISOLATION OF URACIL FROM LIVER. PMID- 17843967 TI - AUTHORITY CITATIONS IN BIOLOGICAL NOMENCLATURE. PMID- 17843968 TI - ISOTOPES OF URANIUM AND LEAD. PMID- 17843969 TI - INDUCTION BY FAST NEUTRONS OF MUTATIONS IN ANTIRRHINUM AND MYOSOTIS. PMID- 17843970 TI - REVERSIBLE INACTIVATION OF PHOSPHATASE. PMID- 17843971 TI - CENTRIFUGING OF LIQUIDS. PMID- 17843972 TI - THE ISOLATION OF A CRYSTALLINE COMPOUND WITH VITAMIN K ACTIVITY. PMID- 17843974 TI - SCIENCE NEWS. PMID- 17843973 TI - THE VELOCITY OF SOUND. PMID- 17843975 TI - THE RECENT CHANGE OF ATTITUDE TOWARD THE LAW OF CAUSE AND EFFECT. PMID- 17843976 TI - PALEONTOLOGY VERSUS DEVRIESIANISM AND GENETICS IN THE FACTORS OF THE EVOLUTION PROBLEM. PMID- 17843977 TI - BIOLOGICAL ABSTRACTS. PMID- 17843978 TI - THE MECHANISM OF CROSSING-OVER. PMID- 17843979 TI - TWISTED TREES. PMID- 17843980 TI - LITERATURE RELATING TO COD LIVER OIL. PMID- 17843981 TI - ADVANCES IN THE BIOLOGICAL SCIENCES. PMID- 17843982 TI - INSCRIPTIONS FOR A SCIENTIFIC BUILDING. PMID- 17843983 TI - THE SHAPOMETER: A DEVICE FOR MEASURING THE SHAPES OF PEBBLES. PMID- 17843984 TI - GROWTH OF PLANTS UNDER CONTINUOUS LIGHT. PMID- 17843986 TI - A MAXIMUM POINT IN AN EFFECT OF PROLONGED X-RAY IRRADIATION UPON DROSOPHILA LARVAE. PMID- 17843985 TI - APPARATUS TO CIRCULATE LIQUID UNDER CONSTANT PRESSURE IN A CLOSED SYSTEM. PMID- 17843987 TI - THE ISOLATION OF NORMAL PROPYL GUAIACOL AS A DEGRADATION PRODUCT OF LIGNIN. PMID- 17843988 TI - THE EFFECT OF SUNLIGHT ON HUMAN BLOOD CELLS. PMID- 17843989 TI - THE HISTORY AND WORK OF THE ARMY MEDICAL LIBRARY. PMID- 17843990 TI - WAVES AND CORPUSCLES IN QUANTUM PHYSICS. PMID- 17843992 TI - THE HEN'S EGG NOT FERTILIZED IN THE OVARY. PMID- 17843991 TI - STRUCTURAL CONTROL OF THE FORM AND DISTRIBUTION OF SINK-HOLES. PMID- 17843993 TI - CONCERNING FOSSIL LEGUMES. PMID- 17843994 TI - A METHOD OF DISPERSAL OF THE BLACK WIDOW SPIDER. PMID- 17843995 TI - GEOLOGICAL SURVEY OF NEWFOUNDLAND REVIVED. PMID- 17843996 TI - THE NATIONAL ASSOCIATION OF SCIENCE WRITERS. PMID- 17843998 TI - LOCALIZED CORTICAL GROWTH AS THE IMMEDIATE CAUSE OF CELL DIVISION. PMID- 17843997 TI - THE THIRTY-THIRD MEETING OF THE ASSOCIATION OF AMERICAN GEOGRAPHERS. PMID- 17843999 TI - HOW CONSISTENT ARE AN INDIVIDUAL'S BRAIN POTENTIALS FROM DAY TO DAY? PMID- 17844000 TI - MICROSTRATIFICATION OF THE WATERS OF INLAND LAKES IN SUMMER. PMID- 17844001 TI - APPARATUS FOR PRODUCING CUMULATIVE AND ORDINARY TYPE KYMOGRAPH RECORDS SIMULTANEOUSLY. PMID- 17844002 TI - USE OF THE LANTERN FOR OBJECTIVE EXAMINATIONS. PMID- 17844005 TI - The Littlest Astronomer. PMID- 17844003 TI - ANOTHER CARBORUNDUM PENCIL. PMID- 17844004 TI - History of Carbon-14. PMID- 17844006 TI - Letters to the Editor. PMID- 17844007 TI - Three Princes of Serendip. PMID- 17844008 TI - Congressional Image of NIH. PMID- 17844010 TI - Chemical Kinetics in Shock Tubs. PMID- 17844009 TI - Congressional Frustration. PMID- 17844011 TI - Appalachians: How a Have-Not Region and People Got That Way Conditions Development Efforts. PMID- 17844012 TI - Sex Attractant of Cabbage Looper, Trichoplusia ni (Hubner). AB - When virgin male cabbage loopers were exposed to filter-paper strips containing an extract from female abdomens, they exhibited a response lasting from 2 to 5 minutes. Gases of a component (or components) of these extracts emanating from a chromatography column attracted the males and then evoked the same response. The attractant is fairly volatile and has relatively low molecular weight. PMID- 17844013 TI - Daily Rhythm of Luciferin Activity in Gonyaulax polyedra. AB - Extracts prepared from Gonyaulax cells harvested late in the 12-hour dark period of an artificial 24-hour day contain as much as four times more luciferin activity than similar extracts prepared during the light period. If cultures are not treated with heat or light to reduce the flashing associated with handling, the time of maximum activity is obscured. PMID- 17844014 TI - Metastable Rubidium Aluminum Silicate with a Hexagonal Sheet Structure. AB - A compound of composition RbAlSi(3)O(8), with a structure of double sheets of silica-alumina tetrahedra with common apices held together by rubidium ions in 12 fold coordination, may be crystallized from a melt by rapid cooling. The compound is an analog of the metastable forms of the calcium, barium, strontium, and lead feldspars. PMID- 17844015 TI - Varved Marine Sediments in a Stagnant Fjord. AB - Varved sediments, containing planktonic marine diatoms, occur in Saanich Inlet, British Columbia. An olive-gray lamina, rich in opal, apparently forms during the bloom of Skeletonema costatum in the spring or summer, after which an olive-black lamina is deposited. PMID- 17844017 TI - Macromolecules. PMID- 17844016 TI - Interpretation of the 3-to 4-Micron Infrared Spectrum of Mars. AB - Infrared reflection spectra have been recorded for a large number of inorganic and organic samples, including minerals and biological specimens, for the purpose of interpreting the 3-to 4-micro spectrum of Mars. A previous suggestion that the Martian bands indicated the presence of carbohydrates is shown not to be a required conclusion. However, no satisfactory explanation is advanced and the problem remains unresolved. PMID- 17844018 TI - Hurricanes and Tropical Meteorology. PMID- 17844020 TI - Recombinant DNA research. PMID- 17844019 TI - Advice on project seafarer. PMID- 17844021 TI - Recombinant DNA research. PMID- 17844023 TI - The paradox of hail suppression. PMID- 17844022 TI - Oil spills. PMID- 17844024 TI - Engineering and society programs in engineering education. PMID- 17844025 TI - Guillain-barre: rare disease paralyzes Swine flu campaign. PMID- 17844026 TI - Nuclear moratorium: study claims that effects would be modest, foresees low growth rate for total energy demand. PMID- 17844027 TI - Science advisory groups gearing up. PMID- 17844028 TI - Adverse drug reactions: monitoring needed of drugs on market. PMID- 17844029 TI - Tosteson new harvard dean: chicago bitter about his leaving. PMID- 17844030 TI - Breeder, arms sales are targets of new lobby group. PMID- 17844031 TI - Nuclear partners: adversity breeds trouble between dow and utility. PMID- 17844032 TI - Oceanography: geochemical tracers offer new insight. PMID- 17844033 TI - The aging heart: changes in function and response to drugs. PMID- 17844035 TI - Trends in pest control. PMID- 17844036 TI - Proteins and nucleotides. PMID- 17844034 TI - An inside view. PMID- 17844037 TI - Earthquake hazard in new England. AB - The earthquake return periods (the mean interoccurrence time) and the probability of earthquake occurrences for southern New England are calculated from the available seismic data for the period 1725 through 1974. For this region the occurrence of larger earthquakes varied with time and the seismic activity was higher in the period 1725 through 1824 than in the next 100 years (1825 through 1924). This variation introduces large uncertainties into calculations of the earthquake hazard. The estimated return period, based on data covering the time period 1725 through 1974, for earthquakes in the southern New England area of intensity VI or greater is 25 years and for intensity VIII or greater is 130 years. PMID- 17844038 TI - Interaction of beggiatoa and rice plant: detoxification of hydrogen sulfide in the rice rhizosphere. AB - Beggiatoa was obtained from six habitats, including four water-saturated soils from rice fields. The isolate of Beggiatoa from Bernard clay, when reinoculated into soil treatments from pure culture, significantly reduced hydrogen sulfide levels in soils and increased oxygen release from rice plants. Rice plants significantly increased Beggiatoa survival in flooded soils. Some hydrogen sulfide was necessary for survival of the Bernard clay isolate; high concentrations of hydrogen sulfide killed the Bernard clay isolate but were tolerated by a Crowley silt loam isolate from Eagle Lake, Texas. The results suggest that Beggiatoa may be an element of wetlands plant ecosystems. PMID- 17844039 TI - Experimental separation of sensory and motor functions in pea tendrils. AB - When illuminated pea tendrils from light-grown plants are rubbed on their abaxial side, they rapidly coil in a spiral fashion. If similar tendrils are held in the dark for 3 days and then rubbed, however, they will not coil until they are subsequently illuminated. They can remain uncoiled in the dark for as long as 2 hours after stimulation, and will still coil immediately when they are illuminated. Tendrils that are rubbed and held at 25 degrees C will coil, but those treated at 5 degrees or 10 degrees C will not. However, tendrils rubbed at 25 degrees C and kept from coiling for an hour at 5 degrees C, will immediately coil when restored to the higher temperature. These observations are interpreted to imply separation of sensory and motor functions. PMID- 17844040 TI - Ocean thermal gradients--a practical source of energy? PMID- 17844041 TI - Ocean thermal gradients--a practical source of energy? PMID- 17844042 TI - Ocean thermal gradients--a practical source of energy? PMID- 17844043 TI - Strange xenon, extinct superheavy elements, and the solar neutrino puzzle. PMID- 17844044 TI - PRODUCTS and MATERIALS. PMID- 17844045 TI - Applications Invited for AAAS Congressional Science Fellowships. PMID- 17844046 TI - ANTHROPOLOGY'S CONTRIBUTION TO INTERRACIAL UNDERSTANDING. PMID- 17844048 TI - THE U. S. NATIONAL MUSEUM. PMID- 17844047 TI - WILMON NEWELL, 1878-1943. PMID- 17844049 TI - THE ANNUAL SESSION OF THE AMERICAN MEDICAL ASSOCIATION. PMID- 17844050 TI - ACQUISITION OF A BIRD COLLECTION BY THE NEW YORK STATE MUSEUM. PMID- 17844051 TI - THE NEW ENGLAND ASSOCIATION OF CHEMISTRY TEACHERS. PMID- 17844053 TI - BASIC BIOLOGY AND GENERAL EDUCATION. PMID- 17844052 TI - IN HONOR OF ALEXANDER PETRUNKEVITCH. PMID- 17844054 TI - GREGOR MENDEL'S EXPERIMENT ON THE NATURE OF FERTILIZATION. PMID- 17844056 TI - STARRING SUBJECTS IN "AMERICAN MEN OF SCIENCE". PMID- 17844057 TI - WARTIME INVESTIGATIONS AT MELLON INSTITUTE. PMID- 17844055 TI - FACILITATE HUMAN ENDEAVOR THROUGH COLLEGE TRAINING IN SCIENTIFIC METHOD. PMID- 17844058 TI - THE RELATOINSHIP OF LYSOZYME TO AVIDIN. PMID- 17844059 TI - ON THE POSSIBLE IDENTITY OF "AVIDIN" AND EGGWHITE LYSOZYME. PMID- 17844060 TI - THE TOXICITY OF ORALLY ADMINISTERED TANNIC ACID. PMID- 17844061 TI - A METHOD FOR PREPARING PERMANENT SLIDES OF THE OVA OF PARASITIC WORMS. PMID- 17844062 TI - THE U. S. SIGNAL SERVICE. PMID- 17844063 TI - THE FRENCH ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17844064 TI - EVIDENCE FROM SOUTHERN NEW ENGLAND AGAINST THE ICEBERG THEORY OF THE DRIFT. PMID- 17844065 TI - THE MAGNETOPHONE. PMID- 17844066 TI - THE WEATHER IN JULY, 1883. PMID- 17844067 TI - THE EARTHQUAKE OF JULY 28, 1883, IN THE ISLAND OF ISCHIA. PMID- 17844068 TI - JULY REPORTS OF STATE WEATHER SERVICES. PMID- 17844069 TI - THE MEETING OF SWISS NATURALISTS. PMID- 17844070 TI - Geology of Philadelphia. PMID- 17844071 TI - SERGEANT FINLEY'S TORNADO STUDIES. PMID- 17844072 TI - The pre-Cambrian rocks of Wales. PMID- 17844073 TI - ZIEGLER'S PATHOLOGICAL ANATOMY. PMID- 17844075 TI - SHALL THEY SURVIVE? PMID- 17844074 TI - ECONOMIC ENTOMOLOGY IN ENGLAND. PMID- 17844077 TI - PLANS OF THE GENERAL ELECTRIC COMPANY FOR A NEW RESEARCH LABORATORY. PMID- 17844076 TI - RAINFALL PERIODICITY IN RELATION TO MALARIA AND AGRICULTURE IN THE NEAR EAST. PMID- 17844078 TI - MERTON B. WAITE. PMID- 17844079 TI - THE AMERICAN GEOPHYSICAL UNION. PMID- 17844080 TI - THE BIOMETRIC BULLETIN. PMID- 17844081 TI - HONORARY DEGREES CONFERRED BY COLUMBIA UNIVERSITY. PMID- 17844082 TI - THE AMERICAN ASTRONOMICAL SOCIETY. PMID- 17844083 TI - WORLD STANDARD AND UNIT FOR PENICILLIN. PMID- 17844084 TI - BOTANICAL WORK OF THE CINCHONA MISSIONS. PMID- 17844085 TI - AZIMUTHAL EQUIDISTANT MAP. PMID- 17844086 TI - EMPLOYMENT AFTER THE WAR. PMID- 17844087 TI - STARS IN AMERICAN MEN OF SCIENCE. PMID- 17844088 TI - PRODUCTION OF IMMUNITY TO DENGUE WITH VIRUS MODIFIED BY PROPAGATION IN MICE. AB - It has been demonstrated that dengue virus can be propagated by intracerebral inoculation in mice. Although initial adaptation to the mouse is a tedious and difficult process, 16 consecutive passages have been achieved already in one series and further passages are in progress. The virus propagated in mice produced dengue in human volunters, but was not pathogenic for cotton rats, hamsters, guinea pigs or rabbits. Although it was evident that even after 2 serial passages in mice the virus produced a modified type of disease in human beings, tests with the 7th, 9th and 10th passage material indicated that the modification had become so marked that it could be used as a vaccine for the production of immunity against dengue. PMID- 17844090 TI - THE PRODUCTION OF CARCINOMA AND SARCOMA IN TRANSPLANTED EMBRYONIC TISSUES. PMID- 17844089 TI - BACTERIOSTATIC AND BACTERICIDAL PROPERTIES OF 2,4-DICHLOROPHENOXYACETIC ACID. PMID- 17844091 TI - ACETYL CHOLINE AND THE ACTIVATION OF MARINE EGGS. PMID- 17844092 TI - THE OXYDASE REACTION IN CHICK EMBRYOS AND BROTH MEDIA CONTAINING NEISSERIA. PMID- 17844093 TI - A MICROBIOLOGICAL AND FLUOROMETRIC TEST FOR MINUTE AMOUNTS OF ALLOXAN. AB - A microbiological and fluorometric test for the determination of minute amounts of alloxan has been described. The test involves the conversion of the alloxan to riboflavin which is measured by microbiological or fluorometric techniques. PMID- 17844094 TI - A HANGING DROP METHOD FOR CONTINUOUS OBSERVATION OF THE ACTIVITY OF ORGANISMS IN CYANIDE. PMID- 17844096 TI - Color associations with the months. PMID- 17844097 TI - Meteoric activity, Aug. 10. PMID- 17844095 TI - COMMENT AND CRITICISM. PMID- 17844098 TI - The classification and paleontology of the U. S. tertiary deposits. PMID- 17844099 TI - A NEW ENDOWMENT FOR RESEARCH. PMID- 17844100 TI - THOMAS ALVA EDISON. PMID- 17844102 TI - A SCHOOL FOR ELECTRICAL ENGINEERING IN BOSTON. PMID- 17844101 TI - THE ELECTRIC RAILWAY IN NEW YORK. PMID- 17844104 TI - INCANDESCENT LAMPS ON RAILWAYS. PMID- 17844103 TI - ELECTRICAL MEASURING INSTRUMENTS. PMID- 17844105 TI - VAN ERMENGEM ON THE CHOLERA MICROBE. PMID- 17844106 TI - CHLOROFORM AS AN ANAESTHETIC. PMID- 17844107 TI - THE FIRST REPORT OF THE AMERICAN SOCIETY FOR PSYCHICAL RESEARCH. PMID- 17844108 TI - ATLAS OF PLANT-DISEASES. PMID- 17844109 TI - UNIVERSITY REGISTRATION STATISTICS. PMID- 17844110 TI - THE PHYSICAL LABORATORY OF THE NATIONAL ELECTRIC LAMP ASSOCIATION. PMID- 17844112 TI - THE INTERNATIONAL CONGRESS ON THE EDUCATION OF CHILDREN AT HOME. PMID- 17844111 TI - THE AMERICAN BREEDERS' ASSOCIATION. PMID- 17844113 TI - THE MINING EXPERIMENT STATION AT THE UNIVERSITY OF NORTH DAKOTA. PMID- 17844115 TI - THE ELIZABETH THOMPSON SCIENCE FUND. PMID- 17844114 TI - THE BOSTON MEETING OF THE AMERICAN ASSOCIATION. PMID- 17844116 TI - THE TEACHING OF ELEMENTARY DYNAMICS IN THE HIGH SCHOOL. PMID- 17844117 TI - INFLUENCE OF OXYGEN ON THE VALUE OF COAL. PMID- 17844118 TI - ALLIGATOR MISSISSIPPIENSIS IN OKLAHOMA. PMID- 17844119 TI - A SIMPLE CLOUD APPARATUS. PMID- 17844120 TI - SYSTEM OF BASKETRY TECHNIC. PMID- 17844121 TI - THE SEPARATED BLASTOMERES OF CENTRIFUGED EGGS OF ARBACIA. PMID- 17844123 TI - THE CONVOCATION WEEK MEETINGS OF SCIENTIFIC SOCIETIES. PMID- 17844122 TI - FUSARIUM WILT OF CABBAGE. PMID- 17844124 TI - THE ADVANCEMENT OF SCIENCE. PMID- 17844125 TI - GENERAL BUSINESS. PMID- 17844126 TI - ADDRESS OF PROFESSOR GEORGE F. BARKER, THE RETIRING PRESIDENT OF THE ASSOCIATION: Some Modern Aspects of Life Question. PMID- 17844127 TI - ON CURRENTS PRODUCED BY FRICTION BETWEEN CONDUCTING SUBSTANCES AND ON A NEW FORM OF TELEPHONE RECEIVER. PMID- 17844128 TI - THE REDUCTION OF CHLORIDE ORES. PMID- 17844129 TI - PHYSICAL NOTES. PMID- 17844130 TI - SECTION 1., ECONOMIC AND SOCIAL SCIENCE. II. PMID- 17844131 TI - THE UPPER TEMPERATURE LIMITS OF LIFE. PMID- 17844132 TI - THE PROPOSED BIOLOGICAL STATION AT THE TORTUGAS. PMID- 17844133 TI - THE ARC OF QUITO. PMID- 17844134 TI - PROGRESS OF THE CONCILIUM BIBLIOGRAPHICUM. PMID- 17844136 TI - THE DALTON CELEBRATIONS AT MANCHESTER. PMID- 17844135 TI - CENTENNIAL CELEBRATION OF THE BIRTHDAY OF JUSTUS VON LIEBIG. PMID- 17844137 TI - TRIGONOMETRIC SURVEY OF BRAZIL. PMID- 17844138 TI - WATER POWER DEVELOPMENT. PMID- 17844139 TI - METABOLISM OF CRYING BABIES. PMID- 17844140 TI - NEW LINES IN ECLIPSE SPECTRUM. PMID- 17844141 TI - DIPHTHERIA. PMID- 17844142 TI - COCAINE ADDICTS. PMID- 17844143 TI - THE PRESENT TENDENCIES AND METHODS OF PHYSIOLOGICAL TEACHING AND RESEARCH. PMID- 17844144 TI - ON THE CONTROL OF THE RAT POPULATION. PMID- 17844146 TI - BUSINESS METHODS. PMID- 17844145 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17844147 TI - SOME COLLOID PHENOMENA IN THE ROCKY MOUNTAINS. PMID- 17844148 TI - SHADOW BANDS. PMID- 17844149 TI - ATTENDANCE AT COUNCIL MEETINGS OF THE AMERICAN ASSOCIATION. PMID- 17844150 TI - GEOLOGICAL OBSERVATIONS ON THE ISLAND OF MAUI, HAWAII. PMID- 17844152 TI - MEDICAL SCIENCES AT THE WASHINGTON MEETING. PMID- 17844153 TI - TRENDS IN MODERN PHYSICS. PMID- 17844151 TI - UNICRYSTALLINE PALLADIUM WIRES. PMID- 17844155 TI - A DOZEN MATHEMATICAL ERRORS IN WEBSTER'S DICTIONARY. PMID- 17844156 TI - THE CHLORINE CONTENT OF THE LEDA CLAY. PMID- 17844154 TI - TEACHING CHEMISTRY FOR ITS CULTURAL AND TRAINING VALUES. PMID- 17844158 TI - THE McDONALD OBSERVATORY. PMID- 17844157 TI - SOME OBSERVATIONS ON SLUMPING AND GULLY FORMATION. PMID- 17844159 TI - SKUNK MORTALITY ON THE HIGHWAY. PMID- 17844161 TI - RAMAN SPECTRA OF AMINES AND METHYLATED AMMONIUM IONS. PMID- 17844160 TI - MATHEMATICAL EXPRESSION OF EQUILIBRIUM BETWEEN NITROGEN AND PHOSPHORIC ACID IN PLANTS. PMID- 17844162 TI - RECOVERY OF VIABLE ADRENAL CORTICAL TISSUE. PMID- 17844163 TI - How Big Is Too Big? PMID- 17844164 TI - Plant Communities: Recent research suggests that they form units in a vegetation continuum rather than discrete classes. PMID- 17844165 TI - Optical Tracking of Artificial Earth Satellites: The Moonwatch program and the precision photographic program supply much of the raw orbit data. PMID- 17844166 TI - News of Science: Rockefeller Panel Urges Education Changes. PMID- 17844167 TI - Ability of Bats to Discriminate Echoes from Louder Noise. PMID- 17844168 TI - Spray Mechanism of the Cockroach Diploptera punctata. PMID- 17844169 TI - "Paramecium Controversy". PMID- 17844170 TI - General Semantics. PMID- 17844171 TI - General Semantics. PMID- 17844172 TI - "Paramecium Controversy". PMID- 17844173 TI - Equipment. PMID- 17844174 TI - Women on college faculties. PMID- 17844175 TI - Grecian concept of entasis. PMID- 17844176 TI - Floating gobs of oil. PMID- 17844177 TI - Postscript. PMID- 17844178 TI - Southeast asian policy. PMID- 17844179 TI - Effect of the draft on graduate physics education. PMID- 17844180 TI - Mind assault. PMID- 17844181 TI - Physics in the twentieth century. PMID- 17844183 TI - VW Foundation: Money Giver on the European Scene. PMID- 17844185 TI - Pyrrhotites: Stoichiometric Compounds with Composition Fen--1Sn (nge8). AB - A new type of natural pyrrhotite, orthorhombic 11C type (a = 6.892, b = 11.952, c = 5.744 x 11 angstroms), and the hexagonal 6C type (a = 6.89, c = 5.76 x 6 angstroms) are described. Their compositions are Fe(10)S(11) and Fe(11)S(12), respectively. Pyrrhotites stable in nature have essentially stoichiometric composition, Fe(n)-(l)S(n) (n>/=8), with the structures of n/2C type for n even and of nC type for n odd. The solid solutions between Fe(11)S(12) and Fe(10)S(11), and between Fe(10)S(11) and Fe(9)S(10) are considered metastable in nature. PMID- 17844184 TI - After cambodia and Kent: academe enters congressional politics. PMID- 17844186 TI - Transcontinental Tidal Gravity Profile across the United States. AB - Data obtained from a transcontinental tidal gravity profile across the United States were analyzed. Results for the principal tidal constituents M(2) and O(1) have shed light on the long-standing problem of the indirect influence of ocean tides on the solid-earth tide. The profile consists of nine observational stations distributed almost evenly around latitudes 39 to 41 degrees north across the United States. The observed values of the gravimetric factor and the phase were found to depend on the tidal characteristics of the Atlantic and Pacific oceans. There is no observable correlation between tidal gravity parameters and the regional geology. When the influence of ocean tides is taken into account, it is possible for the first time to bring the gravimetric factors and phases for all the stations of a transcontinental network into a consistent system within the framework of the earth tidal theory. PMID- 17844187 TI - Mars: occurrence of liquid water. AB - In the absence of juvenile liquid water, condensation of water vapor to ice and subsequent melting of ice are the only means of producing liquid water on the martian surface. However, the evaporation rate is so high that the available heat sources cannot melt pure ice. Liquid water is therefore limited to concentrated solutions of strongly deliquescent salts. PMID- 17844188 TI - Metamorphic waters from the pacific tectonic belt of the west coast of the United States. AB - Waters unusually rich in ammonia, boron, carbon dioxide, hydrogen sulfide, and hydrocarbons are found in more than 100 localities along the Pacific coast of the United States. The waters are believed to be products of low-grade metamorphism of marine sediments. The marine sedimentary rocks would have to be tectonically emplaced below crystalline rocks in many places. Mercury ore deposits are probably also products of the low-grade metamorphism. PMID- 17844189 TI - Megafauna and man from ayacucho, highland peru. AB - Crude unifacial tools, choppers, and a burin have been uncovered in association with megafauna in a buried stratum that was radiocarbon dated at 12,200 B.C. in a cave in highland Peru. The tool types, megafauna, and date are significant with regard to the problem of the antiquity of man and his culture in the New World. PMID- 17844191 TI - Forthcoming events. PMID- 17844190 TI - One-way radar range to the moon. PMID- 17844192 TI - Agricultural aid to indochina. PMID- 17844193 TI - Letters to the editor. PMID- 17844194 TI - Energy production and climate. PMID- 17844195 TI - The big horn medicine wheel. PMID- 17844196 TI - Marine faunal areas. PMID- 17844197 TI - Letters to the editor. PMID- 17844198 TI - Delays in tapping energy sources. PMID- 17844199 TI - Reactions of organ crystals with gases. AB - Although reactions of molecular crystals are much more widespread than has been generally appreciated (53), the great sensitivity of their rates to seemingly trivial changes in molecular structure clearly provides a major stumbling block to the general utilization of such processes. A key to understanding the effects of structural changes has been provided by the demonstration of anisotropy of such reactions discussed in this article. It is recognized, however, that many factors in addition to those aspects of the crystal structure utilized in the discussion above may play a part in determining reactivity of crystalline solids with gases. The recent ready availability of crystal structure data for molecular crystals should lead to a more rapid development of the principles governing the packing of such crystals and their reactivity. The resulting control of such reactions should not only provide the means of causing them when they are desired, as, for example, for synthesis, but also the means of preventing them when they are to be avoided, as in the stabilization of pharmaceuticals. Finally, it appears that we have only just begun to exploit the potential reaction specificity and the exciting possibilities resulting from the unique symmetry properties of the crystalline state. PMID- 17844200 TI - Science advice in the white house? Continuation of a debate. AB - Thus, we are skeptical of the commonly stated arguments for re-creation of a science office at the White House, but are ultimately convinced that such an office is justified. A three-man CST is a reasonable proposal, although the detailed structure is less critical than the mandate given to the office, and the general understanding within government of its functions and limitations and of its relationship to the President. To give it permanence, the office should be grounded in a science policy management and oversight function that is critically needed today. That kind of strong office could lead a president to use it as his personal science advisory staff, but the decision must be made anew by each president. The President does have other ways of obtaining scientific advice, although the right kind of science office would be a preferable route in our view. The importance of such an office being able to present its analyses and recommendations in policy terms useful to other policy-makers cannot be overestimated. This has important implications for the kind of competence required to staff and work with such a council; it also requires recognition of the fact that policy-relevant studies and advice can never be value-free, even when carried out by scientists and engineers. And finally, such a council could bring intensive and continuous attention to the international dimension of U.S. science policy, which seems to us to be particularly neglected. It is not yet clear whether there will be any structural changes in the new Administration. But it is not too soon to be clearer about the essential factors that should underlie a sensible proposal for this or the next Administration. PMID- 17844202 TI - Rocky eyes science advice. PMID- 17844201 TI - In energy impasse, conservation keeps popping up. PMID- 17844203 TI - The environment, a "mature%" cause in need of a lift. PMID- 17844204 TI - FAS Attacks Politicization of NIH. PMID- 17844205 TI - Congress gets on with reform, seeks to reassert itself. PMID- 17844207 TI - Office of science and society programs. PMID- 17844206 TI - Sociobiology (I): models of social behavior. PMID- 17844208 TI - Soapstone artifacts: tracing prehistoric trade patterns in virgimna. AB - Rare earth element abundances in soapstone from quarries and artifacts in eastern Virginia were determined by instrumental neutron activation analysis. By comparing these abundances it was possible to trace artifactual material to the outcrops which served as the source of this material during the first millennium B.C. Certain known sociopolitical boundaries in prehistoric Virginia were inferred to be older than previously assumed. PMID- 17844209 TI - Atmospheric trace metals at remote northern and southern hemisphere sites: pollution or natural? AB - The chemical composition of atmospheric particles collected near sea level over the North Atlantic indicates that Al, Sc, Mn, Fe, Co, Cr, Na, Mg, Ca, K, and Sr are derived from either crustal weathering or the ocean. The elements V, Zn, Cu, Cd, Pb, Sb, and Se are present in concentrations higher than expected from these sources. Although the V is probably derived from pollution sources on the North American continent, a comparison of enrichment factors relative to average crustal material for the remainder of these elements over the North Atlantic with enrichment factors for similar samples collected at the geographic South Pole suggests that the anomalously high enrichment factors may be due to natural rather than anthropogenic sources. A vapor phase for these metals may be involved at their source. PMID- 17844210 TI - Petroleum pollutants in surface and groundwater as indicated by the carbon-14 activity of dissolved organic carbon. AB - The (14)C activity of dissolved organic carbon (DOC) can be used to distinguish between the fossil organic carbon due to petrochemical effluents and modern organic carbon due to domestic wastes and natural decaying organic matter. Rivers polluted by petrochemical effluents show varying amounts of depression of the DOC (14)C activity, reflecting concentrations of (14)C-deficient fossil carbon of as much as about 40 percent of the total DOC. PMID- 17844211 TI - Microwave emission spectrum of the moon: mean global heat flow and average depth of the regolith. AB - Earth-based observations of the lunar microwave brightness temperature spectrum at wavelengths between 5 and 500 centimeters, when reexamined in the light of physical property data derived from the Apollo program, tentatively support the high heat flows measured in situ and indicate that a regolith thickness between 10 and 30 meters may characterize a large portion of the lunar near side. PMID- 17844212 TI - The Postspinel Phases in the Mg2SiO4-Fe2SiO4 System. AB - Samples of olivine (Fo(0)Fa(100), Fo(60)Fa(40), Fo(80)Fa(20), and Fo(100)Fa(0)) and of spinel (Fo(50)Fa(50), Fo(2)Fa(100), where Fo is forsterite and Fa is fayalite) were subjected to pressures up to 250 kilobars in a diamond anvil press and were heated in situ up to ~ 1700 degrees C by an infrared beam from a continuous-wave YAG (yttrium-aluminum-garnet) laser. The brightness temperature was determined from the intensity of incandescence of the sample by means of an optical pyrometer. X-ray diffraction patterns of the samples, obtained after quenching and unloading, show conclusively that these compositions disproportionate to (Mg, Fe)O and SiO(s) (stishovite) under these conditions. PMID- 17844213 TI - Specific elicitors of plant phytoalexin production: detenninants of race specificity in pathogens? AB - Race 1 cultures of the phytopathogenic fungus Phytophthora megasperma var. sojae produced a specific elicitor of the soybean phytoalexin hydroxyphaseollin that resulted in higher production of the phytoalexin on disease-resistant Harosoy 63 soybeans than in the near-isogenic susceptible cultivar Harosoy. Race 3 of the fungus, which gives susceptible reactions on both soybean cultivars, did not produce the race I specific elicitor. PMID- 17844214 TI - Appraising proposed federal standards for water resources investment. PMID- 17844215 TI - PRODUCTS and MATERIALS. PMID- 17844216 TI - THE REPORT OF PRESIDENT TRUMAN ON THE ATOMIC BOMB. PMID- 17844217 TI - MICROSCOPIC AND CHEMICAL PROPERTIES OF PRECANCEROUS LESIONS. PMID- 17844218 TI - MAX BERGMANN 1886-1944. PMID- 17844220 TI - STUDY OF THE CAUSES AND TREATMENT OF CANCER. PMID- 17844219 TI - SCIENCE IN DENMARK AND NORWAY. PMID- 17844222 TI - THE INSTITUTE OF NUCLEAR STUDIES AND THE INSTITUTE OF METALS AT THE UNIVERSITY OF CHICAGO. PMID- 17844221 TI - THE OFFICE OF RESEARCH AND INVENTIONS OF THE NAVY DEPARTMENT. PMID- 17844223 TI - THE IN VITRO PROTECTION OF PENICILLIN FROM INACTIVATION BY PENICILLINASE. AB - (1) A combination of penicillin and immune plasma protein has been obtained which possesses bacteriostatic activity. (2) The presence of the penicillinase immune plasma protein in this mixture protects penicillin in vitro from destruction by penicillinase. PMID- 17844224 TI - THE EFFECT OF THIOURACIL ON THE RESPIRATION OF BONE MARROW AND LEUCOCYTES IN VITRO. PMID- 17844225 TI - ANTAGONISTIC ACTION OF A RED MOULD PIGMENT AGAINST BACTERIA OF THE TYPHOID PARATYPHOID-DYSENTERY GROUP. PMID- 17844226 TI - ACCUMULATION OF DDT IN THE BODY FAT AND ITS APPEARANCE IN THE MILK OF DOGS. PMID- 17844227 TI - THE Rh AND Hr FACTORS IN CHIMPANZEES. PMID- 17844228 TI - A NEW TEST FOR BLOOD ESTROGEN. PMID- 17844229 TI - NORELAC--A SUBSTITUTE FOR SHELLAC IN THE PRESERVATION OF SMOKED PAPER RECORDS. PMID- 17844230 TI - BREAD "ENRICHMENT". PMID- 17844232 TI - ONE-PARENT PROGENY OF TUBIFICID WORMS. PMID- 17844231 TI - BREAD "ENRICHMENT". PMID- 17844233 TI - Meetings & Conferences. PMID- 17844234 TI - Liquid Scintillation Counting of Tritium-labeled Water and Organic Compounds. PMID- 17844236 TI - The Forest Insect Problem. PMID- 17844235 TI - More on Editorial Prerogatives. PMID- 17844237 TI - Employment and Education Fair in Science. PMID- 17844238 TI - Science Teaching in the Secondary Schools. PMID- 17844239 TI - Science versus Administration in Certain U. S. Foreign Aid Efforts. PMID- 17844240 TI - THE FUNCTION OF THE STATE UNIVERSITY. PMID- 17844242 TI - THE MAKING OF LANTERN SLIDES. PMID- 17844241 TI - ORTHOGENETIC VARIATION. PMID- 17844243 TI - THE GEOGRAPHICAL DISTRIBUTION OF STUDENTS. PMID- 17844244 TI - THE OCCURRENCE OF ICHTHYOSAUR-LIKE REMAINS IN THE UPPER CRETACEOUS OF WYOMING. PMID- 17844245 TI - NOTE ON VECTOR SYMBOLS. PMID- 17844246 TI - THE RHODES SCHOLARSHIPS. PMID- 17844247 TI - THE RESEARCH LABORATORY OF PHYSICAL CHEMISTRY OF THE MASSACHUSETTS INSTITUTE OF TECHNOLOGY. PMID- 17844248 TI - THE NEW ORLEANS MEETING OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17844250 TI - THE BRITISH ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE THE ETHNOLOGICAL ANALYSIS OF CULTURE. PMID- 17844249 TI - THE AMERICAN SOCIETY OF NATURALISTS AND AFFILIATED SOCIETIES. PMID- 17844252 TI - APPROPRIATIONS MADE FOR SCIENTIFIC PURPOSES AT THE PORTSMOUTH MEETING OF THE BRITISH ASSOCIATION. PMID- 17844251 TI - THE NEW CHESTNUT BARK DISEASE. PMID- 17844253 TI - THE SCHOOL OF AMERICAN ARCHEOLOGY. PMID- 17844254 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17844255 TI - "WASHINGTON SCIENCE". PMID- 17844257 TI - HOUSE AIR. PMID- 17844256 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17844258 TI - "BIOLOGY". PMID- 17844259 TI - SCIENTIFIC JOURNALS AND ARTICLES. PMID- 17844260 TI - ON SOME CONDITIONS OF TISSUE GROWTH, ESPECIALLY IN CULTURE MEDIA. PMID- 17844261 TI - ON AN INTERPOLATION FORMULA USED IN CALCULATING TEMPERATURE COEFFICIENTS FOR VELOCITY OF VITAL ACTIVITIES, TOGETHER WITH A NOTE ON THE VELOCITY OF NERVE CONDUCTION IN MAN. PMID- 17844262 TI - THE YELLOWSTONE NATIONAL PARK. PMID- 17844263 TI - A NEW SCIENCE OF MIND. PMID- 17844265 TI - EXPLORATIONS IN GREENLAND. PMID- 17844264 TI - ABORIGINAL ARCHITECTURE IN THE SOUTH-WEST. PMID- 17844266 TI - A Proposed Steel 'Vacuum' Balloon. PMID- 17844268 TI - The Tape-Worm in Sheep. PMID- 17844267 TI - SCIENTIFIC NEWS IN WASHINGTON. PMID- 17844270 TI - ELECTRICAL SCIENCE. PMID- 17844269 TI - Death of Prof. E. B. Elliott. PMID- 17844271 TI - HEALTH MATTERS. PMID- 17844272 TI - An Unusual Auroral Bow. PMID- 17844273 TI - Fayette County Meteorite. PMID- 17844274 TI - Indirect aerosol forcing. PMID- 17844275 TI - ARCHAEOLOGY: Paintings in Italian Cave May Be Oldest Yet. AB - Stone slabs bearing images of an animal and a half-human, half-beast figure were uncovered during excavations by an Italian team at the Fumane Cave northwest of Verona. The images are believed to be at least as ancient as some found in the Grotte Chauvet in southern France--the current record holder at 32,000 years--and possibly even older. More important, cave art experts say, the new paintings bolster other evidence that humans engaged in sophisticated symbolic expression much earlier than once thought. PMID- 17844276 TI - EDUCATION: Gates Gives Cambridge a Rival to Rhodes. AB - Thanks to a new $210 million trust announced on 11 October by the Bill & Melinda Gates Foundation, Cambridge University is launching a new high-visibility scholars' program, which each year will fund at least 225 students from outside the United Kingdom. The university will select Gates Cambridge Scholars based on merit, not need, focusing on academic ability and leadership potential. PMID- 17844277 TI - ARCHAEOLOGY: Arizona to Take High Road to Preservation? AB - State transportation officials have agreed to weigh a proposal to set aside a scientifically valuable parcel of a federal highway project for future research rather than excavating it and selling it to the highest bidder. Should it proceed, Arizona could set a new standard of stewardship for government agencies that determine the fate of ancient relics. PMID- 17844278 TI - CHEMISTRY NOBEL: Getting a Charge Out of Plastics. AB - This year's Nobel Prize in chemistry was awarded to a trio of researchers--Alan Heeger of the University of California, Santa Barbara; Alan MacDiarmid of the University of Pennsylvania in Philadelphia; and Hideki Shirakawa of the University of Tsukuba in Japan--for discovering that plastics can be made electrically conductive. The discovery paved the way for revolutionary applications such as full-color displays for cellular phones and plastic electronics for computerized merchandise. PMID- 17844279 TI - ECONOMICS NOBEL: Dealing With Biases and Discrete Choices. AB - This year's Bank of Sweden Prize in Economic Sciences, given in honor of Alfred Nobel, goes to two researchers who gave the field of microeconomics--the study of individuals' economic behavior--new tools to help draw conclusions from imperfect data. James Heckman of the University of Chicago wins half of this year's prize for coming up with ways to deal with selection biases. Daniel McFadden of the University of California, Berkeley, tackled a different conundrum: how to quantify discrete choices rather than continuous ones. PMID- 17844280 TI - Soft money is hard to find. PMID- 17844281 TI - A benefit of being big. PMID- 17844282 TI - Consideration of copollutants. PMID- 17844283 TI - Space station research: details please. PMID- 17844284 TI - MAGNETISM: Magnets Fast and Small. AB - As magnetic devices become smaller and faster, it is becoming increasingly important to understand the dynamics of magnetic domains on small spatial and temporal scales. In their Perspective, Miltat and Thiaville highlight the report by Acremann et al., whose magnetooptical microscope combines state of the art space and time resolution, thus allowing the precessional motion of magnetic domains to be studied directly. The dynamics they observe are complex, indicating that in both the space and time domains, neither the magnetization nor the applied field should be viewed as uniform. PMID- 17844287 TI - Headquarters of the Sections of the AAAS and the Participating Societies. PMID- 17844286 TI - Registration. PMID- 17844288 TI - General Headquarters. PMID- 17844289 TI - Points of Special Interest--Tours, etc. PMID- 17844290 TI - AAAS Prize Awards. PMID- 17844292 TI - AAAS Business Sessions. PMID- 17844291 TI - Press Service of the Association. PMID- 17844293 TI - The Program. PMID- 17844294 TI - Local Committees. PMID- 17844295 TI - Annual Science Exposition. PMID- 17844296 TI - Association Finances. PMID- 17844297 TI - ORGANIZED KNOWLEDGE AND NATIONAL WELFARE. PMID- 17844298 TI - THE PROOF OF MICROBIAL AGENCY IN THE CHEMICAL TRANSFORMATIONS OF SOIL. PMID- 17844299 TI - THE FIRST PUEBLO RUIN IN COLORADO MENTIONED IN SPANISH DOCUMENTS. PMID- 17844300 TI - A NEW METEORITE. PMID- 17844301 TI - TESTS OF RADIATOR HUMIDIFIERS. PMID- 17844302 TI - FILING PAMPHLETS. PMID- 17844303 TI - THE VANISHING INDIAN. PMID- 17844304 TI - ON A SUDDEN OUTBREAK OF COTTON RUST IN TEXAS. PMID- 17844305 TI - THE EFFECTS OF ACIDS AND SALTS ON "BIO-COLLOIDS". PMID- 17844307 TI - Meetings & Conferences. PMID- 17844306 TI - Poliomyelitis Viruses in Tissue Culture. PMID- 17844308 TI - Science in Ireland. PMID- 17844309 TI - Androgenesis with Zygogenesis in Gynandromorphic Honeybees (Apis mellifera L.). PMID- 17844310 TI - Preprotection of Mice against X-Irradiation Mortality by Sodium Nitrite. PMID- 17844311 TI - A Simple Stage-mounted Micromanipulator. PMID- 17844312 TI - Comparative Histological Studies of Endocrine Glands of Yellow (A[unknown]a) and Non-agouti (aa) Mice in Relation to the Problem of Hereditary Obesity. PMID- 17844313 TI - Automatic Microtome. PMID- 17844314 TI - Histochemical Demonstration of 5-Nucleotidase Activity in Cell Nuclei. PMID- 17844315 TI - Areal Differentiation and the "Science" of Geography. PMID- 17844316 TI - Cloudiness in Relation to Choice of Astronomical Sites. PMID- 17844317 TI - The Aeropause. PMID- 17844318 TI - Lipochondria of Living Nerve Cells. PMID- 17844319 TI - COMMENT AND CRITICISM. PMID- 17844320 TI - The faults of south-western Virginia. PMID- 17844321 TI - Assumptions of museum-keepers. PMID- 17844322 TI - Experiments with reflections. PMID- 17844323 TI - Hibernating mammals. PMID- 17844324 TI - THE BIOLOGICAL INSTITUTE AT PHILADELPHIA. PMID- 17844326 TI - A MOUND OF THE KANAWHA VALLEY. PMID- 17844325 TI - THE ENEMIES AND PARASITES OF THE OYSTER, PAST AND PRESENT. PMID- 17844327 TI - THE ICHTHYOLOGICAL PECULIARITIES OF THE BASSALIAN FAUNA. PMID- 17844328 TI - SMITH SOUND, AND ITS EXPLORATION. PMID- 17844329 TI - THE DEEP-SEA FISHES COLLECTED BY THE TALISMAN. PMID- 17844331 TI - THE DEARBORN OBSERVATORY. PMID- 17844330 TI - JOURNEY OF LESSAR TO SERAKS. PMID- 17844332 TI - PALMS. PMID- 17844334 TI - DANIELL'S PRINCIPLES OF PHYSICS. PMID- 17844333 TI - A NEW MOTOR. PMID- 17844335 TI - PROPAGATION OF TUBERCULOSIS. PMID- 17844336 TI - INTELLIGENCE FROM AMERICAN SCIBNTIFIC STATIONS. PMID- 17844337 TI - PRINCIPLES OF CURRICULUM MAKING. PMID- 17844339 TI - THE NEW PERUVIAN EXPEDITION UNDER THE AUSPICES OF YALE UNIVERSITY AND THE NATIONAL GEOGRAPHIC SOCIETY. PMID- 17844338 TI - INDUSTRIAL FELLOWSHIPS OF THE MELLON INSTITUTE. PMID- 17844340 TI - THE COMMITTEE OF ONE HUNDRED ON SCIENTIFIC RESEARCH OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17844341 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17844342 TI - MULTIPLE FACTORS IN HEREDITY. PMID- 17844344 TI - JAVEL WATER--A SIMPLIFIED AND CORRECTED SPELLING. PMID- 17844343 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17844345 TI - ADAPTATION OF THE TAMARISK FOR DRY LANDS. PMID- 17844347 TI - DOCTORATES CONFERRED BY AMERICAN UNIVERSITIES FOR SCIENTIFIC RESEARCH. PMID- 17844346 TI - FINANCIAL STATEMENT OF THE PERMANENT SECRETARY OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17844348 TI - THE BEGINNINGS OF LABORATORY TEACHING IN AMERICA. PMID- 17844349 TI - HYDRAULIC ILLUSTRATION OF THE WHEATESTONE BRIDGE. PMID- 17844350 TI - THE ECHELON SPECTROSCOPE. PMID- 17844351 TI - THE RELATION OF SCIENCE EDUCATION IN THE SECONDARY SCHOOLS TO THAT IN THE COLLEGE AND THE UNIVERSITY. PMID- 17844352 TI - THE LACOE COLLECTION IN THE NATIONAL MUSEUM. PMID- 17844353 TI - A NEW NAME FOR THE GEORGIA OLD FIELD MOUSE. PMID- 17844354 TI - BOTANICAL NOTES. PMID- 17844355 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17844356 TI - SCIENTIFIC NOTES AND NEWS. PMID- 17844358 TI - UNIVERSITY AND EDUCATIONAL NEWS. PMID- 17844357 TI - DISCUSSION AND CORRESPONDENCE. PMID- 17844359 TI - SCIENTIFIC JOURNALS. PMID- 17844360 TI - SOCIETIES AND ACADEMIES. PMID- 17844361 TI - PRELIMINARY MEDICAL EDUCATION. PMID- 17844362 TI - SMELTER SMOKE. PMID- 17844363 TI - HEART ROT OF SASSAFRAS SASSAFRAS CAUSED BY FOMES RIBIS. PMID- 17844364 TI - AN ALLEGED DIPHTHERITIC ANTITOXIN. PMID- 17844365 TI - THE ARTIFICIAL PRODUCTION OF MUTANTS--A SUGGESTION. PMID- 17844366 TI - NOTE ON THE MOVEMENT OF MOISTURE IN SOILS. PMID- 17844367 TI - BOTANICAL NOTES. PMID- 17844368 TI - THE DENSITY OF THE ETHER. PMID- 17844369 TI - THE AMERICAN ELECTROCHEMICAL SOCIETY. PMID- 17844370 TI - PRESENT AND POST-WAR HEALTH PROBLEMS IN CONNECTION WITH PARASITIC DISEASES. PMID- 17844371 TI - EDWARD BENNETT MATHEWS. PMID- 17844372 TI - ADVANCED INSTRUCTION AND RESEARCH IN MECHANICS AT BROWN UNIVERSITY. PMID- 17844374 TI - SCIENTIFIC INSTRUMENTS NEEDED. PMID- 17844373 TI - CHINESE SCIENTIFIC SOCIETIES. PMID- 17844375 TI - NOMINATIONS FOR OFFICERS OF THE AMERICAN INSTITUTE OF ELECTRICAL ENGINEERS. PMID- 17844376 TI - A WESTINGHOUSE RESEARCH GRANT TO PURDUE UNIVERSITY. PMID- 17844377 TI - PURIFICATION AND ANTIBACTERIAL ACTIVITY OF FUMIGACIN AND CLAVACIN. PMID- 17844378 TI - A LAST WORD ON "STARRING". PMID- 17844379 TI - GUAYULE PLANTS WITH LOW CHROMOSOME NUMBERS. PMID- 17844380 TI - FATAL ENCEPHALITIS IN MAN DUE TO THE VENEZUELAN VIRUS OF EQUINE ENCEPHALOMYELITIS IN TRINIDAD. PMID- 17844382 TI - SCIENCE NEWS. PMID- 17844381 TI - MULTIPLE ELECTRODE HOLDER FOR THE HORSLEY-CLARKE INSTRUMENT. PMID- 17844383 TI - THE SOCIAL SCIENCES AND NATIONAL PLANNING. PMID- 17844384 TI - THE DUTCH ELM DISEASE, GRAPHIUM ULMI, IN CONNECTICUT. PMID- 17844385 TI - THE BELGIAN NATIONAL RESEARCH COUNCIL. PMID- 17844386 TI - THE BIOLOGY OF THE BLACK WIDOW SPIDER, LATRODECTUS MACTANS. PMID- 17844387 TI - OAK TREES AND THE WHITE GRUB MENACE. PMID- 17844389 TI - A NEW SOUTH DAKOTA METEORITE. PMID- 17844388 TI - GROUND WATER AND FOREST BELT. PMID- 17844390 TI - THE PRESERVATION OF CARTILAGE. PMID- 17844391 TI - INTRATRACHEAL INOCULATIONS IN THE RAT. PMID- 17844392 TI - THE SIMILARITY BETWEEN FASCIATIONS IN PLANTS AND TUMORS IN ANIMALS AND THEIR GENETIC BASIS. PMID- 17844393 TI - PERMANENT ACETO-CARMINE PREPARATIONS. PMID- 17844394 TI - THE DISINHIBITION OF EXPERIMENTAL EXTINCTION IN THE WHITE RAT. PMID- 17844395 TI - MOTTLED ENAMEL OF DECIDUOUS TEETH. PMID- 17844396 TI - The origins of the laser. PMID- 17844397 TI - Health and habit. PMID- 17844398 TI - Dickens on statistics. PMID- 17844399 TI - Policy for energy. PMID- 17844400 TI - Normal metallic point contacts. AB - The measured voltage derivative of the nonlinear resistance of tiny point contacts can be separated into a phonon-emission effect (alpha(2)F) and an analytic functional form (background effect). The alpha(2)F's show structure coincident with bulk phonon densities of states. Values of the integral of 2 alpha(2)F/omega are closely related to literature values. The background effect is related to the impurity concentration of the materials. PMID- 17844401 TI - Solar biomass energy: an overview of u.s. Potential. AB - The U.S. annual biomass production for food, lumber, paper, and fiber, if used exclusively for energy, would provide 25 percent of current energy requirements. The collection of unharvested wood residues and cull trees for direct use as fuel for small nearby space-heating applications-especially for peak winter conditions is an important near-term solar energy opportunity. Improved management of hundreds of millions of acres of productive forest land is an important opportunity for the long term. Harvest of cropland residues for energy values, new biomass production using intensive short-rotation silviculture, resubstitution of natural products for petroleum-based synthetics, and forest management for large-scale production of electricity and synthetic fuels are judged to be less appropriate directions for the U.S. energy system to take. PMID- 17844403 TI - Trouble even in new Mexico for nuclear waste disposal. PMID- 17844402 TI - The criminal insanity defense is placed on trial in new york. PMID- 17844404 TI - Like bank robbers, criminal polluters will be prosecuted. PMID- 17844405 TI - United States and bulgaria to cooperate in research. PMID- 17844406 TI - Fermilab director resigns: cites subminimal funding. PMID- 17844407 TI - Bird Lovers and Bureaucrats at Loggerheads over Peregrine Falcon. PMID- 17844409 TI - Liposomes: research applications grow. PMID- 17844408 TI - Old boy system produces geologic survey chief. PMID- 17844410 TI - Animal communication: a summing up. PMID- 17844411 TI - Changes in mortality. PMID- 17844412 TI - Redrecting cognitive science. PMID- 17844413 TI - Observational cosmology. PMID- 17844414 TI - The upper atmosphere. PMID- 17844415 TI - Hemoglobins and their disorders. PMID- 17844416 TI - Ocean eddies generated by seamounts in the north pacific. AB - Small-scale (diameters of about 37 kilometers) fluctuations in dynamic topography north of Hawaii along 158 degrees W are well correlated with upstream seamounts. The fluctuations are subsurface but are manifested as baroclinic eddies at the sea surface. These eddies are confirmed by direct observations and supported by theoretical considerations. The eddies cause small-scale variability in the currents and hydrographic structures in this area, and they should be considered in any sampling programs of the region. PMID- 17844417 TI - Mount agung eruption provides test of a global climatic perturbation. AB - The Mount Agung volcanic eruption in 1963 provides the best-documented global radiative perturbation to the earth's atmosphere currently available. Data on stratospheric aerosols produced by this eruption have been used as input to a model for the atmospheric thermal structure. The computed magnitude, sign, and phase lag of the temperature changes in both the stratosphere and the troposphere are in good agreement with observations, providing evidence that the climatic response to a global radiative perturbation is significant, as well as support for the use of theoretical models to predict climatic effects. PMID- 17844418 TI - Assembly of greek marble inscriptions by isotopic methods. AB - Classical Greek inscriptions cut in marble, whose association as original stelai by archeological methods was debatable, were selected for study. Using traditional geological techniques and determinations of the per mil increments in carbon-13 and oxygen-18, it was determined that fragments could be positively assigned to three stelai, but that fragments from three other stelai had been incorrectly associated. PMID- 17844420 TI - Gordon research conferences. PMID- 17844419 TI - Cell walls of crown-gall tumors and embryonic plant tissues lack agrobacterium adherence sites. AB - Crown-gall tumor initiation by Agrobacterium tumefaciens is inhibited by cell walls from normal dicotyledonous plants but not by cell walls from crown-gall tumors apparently because of bacterial adherence or nonadherence, respectively, to the different cell walls. Cell walls from normal and tumor tissues in culture also show this difference, indicating that the two types of tissue stably maintain this difference under these conditions. Habituated tissue cultures, which resemble crown-gall tumor cultures, however, form cell walls that are inhibitory like those of the normal cultures from which they are derived. Monocotyledonous plants do not act as hosts for Agrobacterium and bacteria specific inhibition is not shown by cell walls from several species of grass, a monocot family. Cell wallsfrom "embryonic" tissues (dicot seedlings less than 2 centimeters long), unlike those from older seedlings, are non-inhibitory. Crown gall tumors thus resemble embryonic tissues in this respect. PMID- 17844422 TI - PRODUCTS and MATERIALS. PMID- 17844421 TI - Program summary, gordon research conferences 1978 schedule--new hampshire and california. PMID- 17844423 TI - AMERICAN PUBLIC HEALTH ASSOCIATION. PMID- 17844424 TI - PHYSICAL TRAINING. PMID- 17844425 TI - THE ALASKAN SOCIETY OF SITKA. PMID- 17844426 TI - HEALTH MATTERS. PMID- 17844427 TI - 'Eskimo and the Indian.'. PMID- 17844428 TI - Rock Specimens from Cumberland Sound. Baffin Land. PMID- 17844429 TI - METEOR-FALL. PMID- 17844430 TI - WHO FIRST SAID IT? PMID- 17844431 TI - The Eskimo Tribes. PMID- 17844432 TI - SCIENCE NEWS. PMID- 17844433 TI - DIPOLE ATTRACTION AND HYDROGEN BOND FORMATION IN THEIR RELATION TO SOLUBILITY. PMID- 17844434 TI - WOMEN IN SCIENCE. PMID- 17844435 TI - SELENIUM IN NUTRITION. PMID- 17844436 TI - DEEP-FOCUS EARTHQUAKES AND ISOSTASY. PMID- 17844437 TI - TERMITES IN CENTRAL NEW YORK STATE. PMID- 17844439 TI - THE TENNESSEE ACADEMY OF SCIENCE. PMID- 17844438 TI - NORTH AMERICAN FISH-HOOKS. PMID- 17844440 TI - SPECTROSCOPIC SIMILARITY BETWEEN ERGOT (LYSERGIC ACID) AND THE YOHIMBINE ALKALOIDS. PMID- 17844441 TI - THE OKLAHOMA ACADEMY OF SCIENCE. PMID- 17844442 TI - THE ERGOT ALKALOIDS. THE STRUCTURE OF LYSERGIC ACID. PMID- 17844443 TI - CARDBOARD FOR ANATOMIC RECONSTRUCTION MODELS. PMID- 17844444 TI - THE CHROMOSOMES OF DROSOPHILA ANANASSAE. PMID- 17844445 TI - AN IMPROVED THERMOREGULATOR. PMID- 17844446 TI - Nuclear Magnetism in Relation to Problems of the Liquid and Solid States. PMID- 17844447 TI - Correction. AB - In describing the cover photo of the March 26 issue we neglected to state that the underwater photograph of the sea spider was taken from the Atlantis of the Woods Hole Oceanographic Institution. PMID- 17844448 TI - The Native Proteins as Polycondensations of Amino Acids. PMID- 17844449 TI - Taxonomic Characteristics for Amoebae. PMID- 17844450 TI - Ultraviolet Light-Absorption of Alkali-treated Solutions of Carbohydrates. PMID- 17844451 TI - Total White Cell Counts of Peripheral and Heart Blood of the Rat. PMID- 17844452 TI - Hemolysis of Human Red Cells by Saponin Following Viral Action. PMID- 17844453 TI - Apparatus for Partition Chromatography on Paper. PMID- 17844454 TI - Photograms of Small Bones and Skulls. PMID- 17844455 TI - A Turbidimeter for the Measurement of the Solubility of Slightly Soluble Liquids. PMID- 17844456 TI - SYSTEMATIC ZOOLOGY: ITS PROGRESS AND PURPOSE. PMID- 17844457 TI - A PLAN OF PUBLICATION FOR AGRICULTURAL EXPERIMENT STATION INVESTIGATIONS. PMID- 17844458 TI - THE SPARK CHRONOSCOPE. PMID- 17844460 TI - A VECTOR DIAGRAM. PMID- 17844459 TI - ON THE EFFECTS OF MAGNESIUM SULPHATE ON PLANTS. PMID- 17844461 TI - ABSTRACTS FOR EVOLUTIONISTS. PMID- 17844462 TI - CURRENT NOTES ON METEOROLOGY AND CLIMATOLOGY. PMID- 17844463 TI - THE DISTRIBUTION OF RADIUM IN THE ROCKS OF THE SIMPLON TUNNEL. PMID- 17844464 TI - THE ARC OF PERU. PMID- 17844465 TI - REPORT OF THE INTERNATIONAL COMMISSION ON ZOOLOGICAL NOMENCLATURE. PMID- 17844466 TI - WILBUR OLIN ATWATER. PMID- 17844467 TI - THE EARLY TERTIARY VOLCAINOES OF THE ABSAROKA RANGE. PMID- 17844468 TI - THE PHYSIOLOGICAL BASIS OF MENTAL LIFE. PMID- 17844469 TI - SOPHUS LIE. PMID- 17844470 TI - THE ORIGIN OF NIGHTMARE. PMID- 17844471 TI - ON THE MAKING OF SOLUTIONS. PMID- 17844472 TI - A NEW SATELLITE OF SATURN. PMID- 17844473 TI - NOTES ON INORGANIC CHEMISTRY. PMID- 17844474 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17844475 TI - CARBONIC ACID IN DEATH GULCH. PMID- 17844476 TI - ZOOLOGICAL NOTES. PMID- 17844477 TI - UNIVERSITY REGISTRATION STATISTICS. PMID- 17844478 TI - VARIATIONS INDUCED IN LARVAL, PUPAL AND IMAGINAL STAGES OF BOMBYX MORI BY CONTROLLED VARYING FOOD SUPPLY. PMID- 17844479 TI - THE CHEMISTRY OF SOILS AS RELATED TO CROP PRODUCTION. PMID- 17844480 TI - THE HEREDITY OF 'ANGORA' COAT IN MAMMALS. PMID- 17844481 TI - ABSORBED GASES AND VULCANISM. PMID- 17844483 TI - THE CONGRESS OF ARTS AND SCIENCE OF THE ST. LOUIS EXPOSITION. PMID- 17844482 TI - CONCERNING MOSQUITO MIGRATIONS. PMID- 17844484 TI - THE AMERICAN SOCIETY OF NATURALISTS. PMID- 17844485 TI - WORLD CULTURE 5000 YEARS AGO. PMID- 17844486 TI - SETTING A WATCH BY THE STARS. PMID- 17844488 TI - SUNLIGHT AND VITAMIN "D" IN EGGS. PMID- 17844487 TI - SMELTER ELIMINATION. PMID- 17844490 TI - INCREASE OF THE INDIAN POPULATION OF THE UNITED STATES. PMID- 17844489 TI - SHADOW BANDS. PMID- 17844491 TI - WHAT MAKES WATER FLOW UPHILL? PMID- 17844492 TI - MARINE BIOLOGICAL LABORATORY DEDICATION EXERCISES, JULY 3, 1925. PMID- 17844493 TI - UNIVERSITY AND EDUCATIONAL NOTES. PMID- 17844494 TI - WHEN DOES WINTER COME? PMID- 17844495 TI - HONEY BEES AND PERFORATED FLOWERS. PMID- 17844496 TI - A NOTE ON A ROT OF THE SMYRNA FIG IN CALIFORNIA. PMID- 17844497 TI - REACTION OF OPALINAS TO VARIOUS LABORATORY MEDIA. PMID- 17844498 TI - SURFACE TENSION DETERMINED BY THE RING METHOD. PMID- 17844499 TI - SEX DIFFERENCE, IN EMOTIONAL OUTLETS. PMID- 17844500 TI - A Federal Program in Applied Mathematics. PMID- 17844501 TI - Alfred North Whitehead, 1861-1947. PMID- 17844502 TI - A Synthesis of Coniferyl Alcohol. PMID- 17844503 TI - A Museum of the Social Sciences. PMID- 17844504 TI - Production of Mesons by the 184-Inch Berkeley Cyclotron. PMID- 17844505 TI - The Immediate Pressor Effect of Desoxycorticosterone Acetate. PMID- 17844507 TI - Sorption of Fumigant Vapors by Soil. PMID- 17844506 TI - The Nasal Cavity of the Rat in Pharmacological and Other Experimentation. PMID- 17844508 TI - Staining of the Stem Tissue of Plants by Triphenyltetrazolium Chloride. PMID- 17844509 TI - Susceptibility of DDT-resistant Houseflies to Other Insecticidal Sprays. PMID- 17844510 TI - Development of a Strain of Houseflies Resistant to DDT. PMID- 17844511 TI - A Simplified Diffusion-Dehydration Technique in the Microtomy of Tissues. PMID- 17844512 TI - Effect of Acetone and Alcohol Fixation and Paraffin Embedding on Activity of Acid and Alkaline Phosphatases in Rat Tissues. PMID- 17844513 TI - A Simple Stereoscope for Viewing Double-Lens Camera Stereographs Without Transposition. PMID- 17844514 TI - SECTION B. PHYSICS. PMID- 17844515 TI - SECTION C. CHEMISTRY. PMID- 17844516 TI - SECTION D. MECHANICAL SCIENCE AND ENGINEERING. PMID- 17844517 TI - DEVELOPMENT OF VEGETABLE PHYSIOLOGY. PMID- 17844518 TI - CURRENT NOTES ON PHYSIOGRAPHY (XVI.). PMID- 17844519 TI - PRELIMINARY NOTE ON A CONTAGIOUS INSECT DISEASE. PMID- 17844520 TI - ARE CONSEQUENCES EVER A TEST OF TRUTH? PMID- 17844521 TI - THE KATYDID'S ORCHESTRA. PMID- 17844522 TI - THE FIRST FORTY YEARS OF THE SOCIETY OF AMERICAN BACTERIOLOGISTS. PMID- 17844523 TI - A MODERN PIONEER. PMID- 17844525 TI - ALFRED GEORGE JACQUES. PMID- 17844524 TI - THE STORY OF SHORT WAVES. PMID- 17844526 TI - FREDERIC SCHILLER LEE. PMID- 17844527 TI - ANNUAL REPORT OF THE DIRECTOR OF THE NEW YORK BOTANICAL GARDEN. PMID- 17844528 TI - THE SUMMER MEETINGS OF BOTANISTS. PMID- 17844530 TI - ENLARGEMENT OF THE CHEMISTRY BUILDING OF THE UNIVERSITY OF CINCINNATI. PMID- 17844529 TI - OFFICERS OF THE WASHINGTON ACADEMY OF SCIENCES. PMID- 17844531 TI - THE AMERICAN CHEMICAL SOCIETY AND DR. SPRINGER. PMID- 17844533 TI - THE USEFULNESS OF BIOLOGICAL ABSTRACTS. PMID- 17844532 TI - AN ENDEMIC PALM ON COCOS ISLAND NEAR PANAMA MISTAKEN FOR THE COCONUT PALM. PMID- 17844534 TI - MOMENTUM AND ENERGY. PMID- 17844535 TI - THE TENNESSEE ACADEMY OF SCIENCE. PMID- 17844536 TI - RESONANCE AND THE CHEMISTRY OF HISTIDINE. PMID- 17844537 TI - FURTHER EVIDENCE OF SEX VARIATION IN THE UTILIZATION OF IRON BY ANEMIC RATS. PMID- 17844538 TI - ON THE ORIGIN OF UROGASTRONE. PMID- 17844539 TI - A ROLLER BOTTLE TISSUE CULTURE SYSTEM. PMID- 17844540 TI - THE USE OF A TRANSLONGITOME IN MAKING AND INTERPRETING ALTERNATE TRANSVERSE AND LONGITUDINAL SERIAL SECTIONS. PMID- 17844541 TI - THE PROMISE OF TECHNOLOGY. PMID- 17844543 TI - PRESIDENTIAL ADDRESS AT THE ANNUAL MEETING OF THE ROYAL SOCIETY. PMID- 17844542 TI - SCIENTIFIC RESEARCH AND THE WAR EFFORT OF U.S.S.R. PMID- 17844544 TI - THE SCIENTIFIC STUDY AND DEVELOPMENT OF PHYSICAL MEDICINE. PMID- 17844545 TI - REPORT OF THE INTERNATIONAL BOARD OF INQUIRY FOR THE GREAT LAKES FISHERIES. PMID- 17844546 TI - PROFESSOR FRANK R. LILLIE AND THE MARINE BIOLOGICAL LABORATORY. PMID- 17844547 TI - GRANTS OF THE COMMITTEE ON RESEARCH OF THE AMERICAN MEDICAL ASSOCIATION. PMID- 17844548 TI - LICENSING THE REPUBLICATION OF FOREIGN ORIGIN MATHEMATICAL TABLES. PMID- 17844549 TI - THE ORIGIN OF LANGUAGE. PMID- 17844550 TI - ACTION OF CLARASE UPON PENICILLIN. PMID- 17844551 TI - THE IDENTITY OF CLAVACIN WITH PATULIN. PMID- 17844552 TI - THE EFFECT OF pH ON THE AVAILABILITY OF p-AMINOBENZOIC ACID TO NEUROSPORA CRASSA. PMID- 17844553 TI - RAPID AND STERILIZING EFFECT OF PENICILLIN SODIUM IN EXPERIMENTAL RELAPSING FEVER INFECTIONS AND ITS INEFFECTIVENESS IN THE TREATMENT OF TRYPANOSOMIASIS (TRYPANOSOMA LEWISI) AND TOXOPLASMOSIS. PMID- 17844554 TI - HEPATIC DYSFUNCTION IN MALARIA. PMID- 17844555 TI - PENICILLIN ASSAY Outline of Four-Hour Turbidimetric Method. PMID- 17844556 TI - Chromatography: A Perspective. PMID- 17844557 TI - The Proteins of Mammalian Spermatozoa and Cellular Nuclei. PMID- 17844558 TI - A Possible Standard for Radioiodine. PMID- 17844559 TI - The Inhibition of the Cholinesterase Activity of Human Blood Plasma by Neutral Phosphate Esters. II: Studies with Hexa 1-C14-Ethyl Tetrapolyphosphate. PMID- 17844560 TI - Iron Metabolism. Heme Synthesis in Vitro by Immature Erythrocytes. PMID- 17844561 TI - Freezing of Whole Blood. PMID- 17844562 TI - A "Free Manometer" Method of Using the Standard Warburg Apparatus. PMID- 17844563 TI - A Method of Optically Recording Contractions and Electrocardiograms from Isolated Frog Hearts. PMID- 17844564 TI - Differentiation of Aragonite from Calcite by Differential Thermal Analysis. PMID- 17844565 TI - Hydrolysis of Adenosine Triphosphate by Trichloracetic Acid. PMID- 17844566 TI - Calibration of Warburg Manometers. PMID- 17844567 TI - Use of Omental Spread in Biological and Pathological Studies. PMID- 17844568 TI - The Preparation of Graphs for Publication. PMID- 17844569 TI - Oral Stress and Meaning in Printed Material. PMID- 17844571 TI - Publications Received. PMID- 17844570 TI - Correction. AB - Referring to my paper "Microcrystallographic Data on Sodium-d-Glutamate (Monosodium Glutamate)", Science, 1949, 110, 304, Dr. B. F. Buchanan, International Minerals & Chemical Corporation, Chicago, informs me that the monosodium glutamate upon which this study was made is the l-form and should be designated as sodium-l-glutamate, being the monohydrate with the following empirical formula: C(5)H(8)O(4)NNa . H(2)O. PMID- 17844572 TI - Meetings & Conferences. PMID- 17844574 TI - ON THE FORMATION OF LAKE BALLS. PMID- 17844573 TI - THE BODILY EXPRESSION OF HUMAN GROWTH AND WELFARE. PMID- 17844575 TI - THE SOLDADO ROCK SECTION. PMID- 17844576 TI - AN APPEAL TO SCIENTISTS OF THE USSR. PMID- 17844577 TI - UNISEXUAL LIMBER PINES. PMID- 17844578 TI - A PERSONAL REPORT ON THE NATIONAL FORESTS. PMID- 17844579 TI - FURTHER OBSERVATIONS ON THE POTENTIAL RHYTHMS OF THE CEREBRAL CORTEX DURING SLEEP. PMID- 17844580 TI - INTRANASAL OR GASTROINTESTINAL PORTAL OF ENTRY IN POLIOMYELITIS. PMID- 17844581 TI - A THYRATRON CONTROL FOR INCUBATORS AND WATER BATHS. PMID- 17844582 TI - HEMORRHAGIC NECROSIS AND REGRESSION SARCOMA 180. PMID- 17844583 TI - THE PREPARATION OF BIXIN. PMID- 17844584 TI - STEAM-JACKET EFFICIENCY. PMID- 17844585 TI - LOCUSTS IN ALGERIA. PMID- 17844586 TI - THE PREVAILING FEVERS OF CHINA. PMID- 17844588 TI - SCIENTIFIC EXPEDITION TO SOUTH MARYLAND. PMID- 17844587 TI - THE STRUCTURE AND PHYSICAL PROPERTIES OF SOILS. PMID- 17844590 TI - THE MARYLAND WEATHER SERVICE. PMID- 17844589 TI - COAL IN THE SHAN STATES. PMID- 17844591 TI - Eddies in the Atmosphere. PMID- 17844592 TI - Radiation-induced health effects. PMID- 17844594 TI - Unesco and nongovernmental organizations. PMID- 17844593 TI - Metabolic precursors of a known human carcinogen. PMID- 17844595 TI - Unesco and nongovernmental organizations. PMID- 17844596 TI - Radiation-induced health effects. PMID- 17844597 TI - Page charges: shifting the burden. PMID- 17844598 TI - Technology transfer. PMID- 17844599 TI - California current eddy formation: ship, air, and satellite results. AB - Until recently, quantitative measurements of the circulation of the California Current were limited to hydrographic determinations [See figure in the PDF file] of temperature and salinity. This information is now being augmented by satellite data. Clouds permitting, satellite scanner systems can locate major ocean frontal boundaries if they are associated with even quite weak horizontal sea-surface temperature gradients. The satellite data are most usefully interpreted in a region such as that encompassing the California Current, where the surface and main thermocline temperature distributions bear some relation to each other. In such a region, it is possible to make interpretations of circulation based on satellite-derived sea-surface temperature patterns. The correctness of these interpretations depends heavily on the availability of historical and present-day subsurface data, collected by conventional methods from ships and aircraft. Satellite infrared scanners, in addition to providing information on circulation with vastly increased spatial resolution, have the potential (with cooperative weather) for providing increased time resolution. These improvements in resolution have permitted us to see that much of the spatial variation in the California Current takes place along welldefined fronts and to observe the evolution of one particular meander. PMID- 17844600 TI - Form and origin of the parry arcs. PMID- 17844601 TI - Economic models in ecology. PMID- 17844602 TI - Ford's Farewell Budget: Science Fares Quite Well. PMID- 17844603 TI - NIH Budget on the Decline. PMID- 17844604 TI - Carter Says No to Cooper; Fredrickson's Future Unsure. PMID- 17844605 TI - Soviet Grain Harvests: CIA Study Pessimistic on Effects of Weather. PMID- 17844607 TI - Ian McHarg: Champion for Design with Nature. PMID- 17844606 TI - Dicing with nature: three narrow escapes. PMID- 17844608 TI - Academy Study Finds Low Energy Growth Won't Be Painful. PMID- 17844609 TI - Sexual dimorphism and mating systems: how did they evolve? PMID- 17844610 TI - X-ray Crystallography: 3-D Structures by Optical Computing. PMID- 17844612 TI - Meeting a pollution challenge. PMID- 17844611 TI - Science in the context of puritan society. PMID- 17844613 TI - Phagocytic cells. PMID- 17844615 TI - PRODUCTS and MATERIALS. PMID- 17844614 TI - Evolutionary phytochemistry. PMID- 17844616 TI - ALBERT BENJAMIN PRESCOTT. PMID- 17844617 TI - THE USE OF COPPER IN THE PURIFICATION OF WATER SUPPLIES. PMID- 17844618 TI - AN ALTERNATIVE INTERPRETATION OF THE ORIGIN OF GYNANDROMORPHOUS INSECTS. PMID- 17844619 TI - NATURAL MOUNDS. PMID- 17844620 TI - THE TOTAL SOLAR ECLIPSE OF AUGUST 29-30, 1905. PMID- 17844621 TI - THE USE OF ISOTOPES AS INDICATORS IN BIOLOGICAL RESEARCH. PMID- 17844622 TI - ETYMOLOGY AND PRONUNCIATION OF THE WORD "OESTRUS" AND ITS DERIVATIVES. PMID- 17844623 TI - CARBONATION VS. CARBONATIZATION. PMID- 17844624 TI - ABNORMAL FEVER CASES. PMID- 17844625 TI - A CASE OF INCORRECT IDENTIFICATION. PMID- 17844626 TI - SEEDLESSNESS IN TOMATOES. PMID- 17844627 TI - THE ISOLATION OF A HOMOGENEOUS HEAVY PROTEIN FROM VIRUS-INDUCED RABBIT PAPILLOMAS. PMID- 17844628 TI - ACETYLATION OF PARA-AMINOBENZENESULFONAMIDE IN THE ANIMAL ORGANISM. PMID- 17844629 TI - DIFFRACTION OF X-RAYS AT VERY SMALL ANGLES BY CELLULOSES AND RAYONS. PMID- 17844631 TI - POTENTIAL MEASUREMENTS IN OXIDO-REDUCTION MIXTURES. PMID- 17844630 TI - SECONDARY INCREASE OF LENGTH OF STRETCHED CHILLED RUBBER. PMID- 17844632 TI - THE FLAGELLA OF PERANEMA. PMID- 17844633 TI - MUSEUM LABELS. PMID- 17844634 TI - Cholesterol crystal embolization. PMID- 17844635 TI - Marburg haemorrhagic fever, Uganda--update. PMID- 17844636 TI - Performance of acute flaccid paralysis (AFP) surveillance and incidence of poliomyelitis, 2007 (data received in WHO headquarters as of 21 August 2007). PMID- 17844637 TI - [Lupus erythematosus. Acute afebrile diffuse outbreak]. PMID- 17844638 TI - Everything old is new again: the use of gender-based terrorism against women. PMID- 17844639 TI - [The natural sciences and the founding of the faculty of biotechnology]. PMID- 17844640 TI - Social rights and social security: the Swedish welfare state, 1900-2000. PMID- 17844641 TI - The Icelandic welfare state in the twentieth century. PMID- 17844642 TI - The Nordic welfare state in Finland. PMID- 17844643 TI - The Social Democrats and the Norwegian welfare state: some perspectives. PMID- 17844644 TI - Debriefing after a crisis. PMID- 17844647 TI - Food for thought ... on validation. PMID- 17844648 TI - Waging war on obesity. PMID- 17844649 TI - Rabies prevention a worldwide effort. PMID- 17844650 TI - Bibliography. Current world literature. Laryngology and bronchoesophagology. PMID- 17844652 TI - Bibliography. Current world literature. Paediatric urology. PMID- 17844651 TI - Bibliography. Current world literature. Prenatal diagnosis. PMID- 17844653 TI - New hope for addicts? An epilepsy drug may help alcoholics stop drinking. PMID- 17844656 TI - Metal complexes of thiazyl radicals. AB - A diverse variety of thiazyl radicals is known. Intense study of these heterocycles continues in the pursuit of molecule-based materials with novel, academically interesting, and technologically relevant properties. Coordination of these species to metal atoms and ions has focused primarily on the 1,2,3,5 dithiadiazolyl 2 and 1,3,2-dithiazolyl 6. The potential of these two heterocycles as ligand building-blocks has, by no means, been fully exploited. From the structural and electronic similarities between 2 and the verdazyl and nitronyl nitroxide radicals, it is apparent that similar radical ligand designs ought to be achievable. The sulfur atoms of 2 lend a unique feature to this radical that may yet be employed as a means of controlling intermolecular interactions or developing multi-metal species. The recent report of sulfur coordination to 6 demonstrates that there is yet more design flexibility available from this thiazyl as well. Coordination complexes of other radical thiazyls have begun appearing in the literature. This field is currently in its infancy and is starting to be recognized as an enormous source of untapped potential in the future development of molecule-based materials. PMID- 17844657 TI - Synthesis, structure and coordination of the ambiphilic ligand (2-picolyl)BCy2. AB - The new pyridine-borane compound (2-picolyl)BCy2, readily prepared from 2 picolyllithium and ClBCy2, adopts a head-to-tail dimeric structure in the solid state as indicated by X-ray diffraction analysis and according to NMR and DFT studies, the dimeric form equilibrates in solution with a strained monomeric structure; the ambiphilic behavior of the new compound is illustrated by its bridging coordination to the (p-cymene)RuCl2 unit. PMID- 17844658 TI - A CNT-like coordination tube with cyano-bridges. AB - Reaction of K2[Ru(bipy)(CN)4] with MnCl2 produces a novel bimetallic compound {Mn(H2O)2[Ru(bipy)(CN)4]} (bipy = 2,2'-bipydine), exhibiting a CNT-like structure bridged by cyanide groups and high thermal stability, which has been first observed in coordination polymers. PMID- 17844659 TI - Ferrocene-containing [2]- and [3]rotaxanes. Preparation via an end-capping cross metathesis reaction and electrochemical properties. AB - Cross-metathesis reactions of terminal olefins with acrylic esters catalyzed by a Ru-carbene complex ((H2IMes)(PCy3)Cl2Ru = CHPh, H2IMes = N,N-bis(mesityl)-4,5 dihydroimidazol-2-ylidene) were applied to the end-capping of [2]pseudorotaxanes composed of dibenzo[24]crown-8 (DB24C8) and ferrocenylmethylammonium derivatives as the macrocyclic and axle components. A [3]rotaxane consisting of two DB24C8s and an axle molecule having ferrocenyl groups at both ends was obtained from the cross-metathesis reaction of two [2]pseudorotaxanes with Fe(C5H4CH2OCOCH = CH2)2. Cyclic voltammograms of the ferrocene-containing rotaxanes show reversible redox reactions whose potentials vary depending on the presence or absence of cationic dialkylammonium groups in the vicinity of the ferrocene units. PMID- 17844660 TI - C-H and P-C(Ph) activation competitive processes caused by interaction with the solvate [cis-Pt(C6F5)2(thf)2]. AB - The study of the reaction between the ethylene [Pt(eta-H2C = CH2)(PPh3)2] or alkyne [Pt(eta2-HC [triple bond] CR)(PPh3)2] (R = SiMe3 1, Bu(t) 2) complexes with [cis-Pt(C6F5)2(thf)2] (thf = tetrahydrofuran) has enabled us to observe the existence of competitive processes between the activation of a P-C(Ph) bond on the PPh3 ligand, to give the binuclear derivative [cis-(C6F5)2Pt(mu-Ph)(mu PPh2)Pt(PPh3)] 3, and the activation of a C-H bond of the unsaturated group, to give the corresponding (mu-hydride)(mu-vinyl) [cis, cis-(PPh3)2Pt(mu-H)(mu 1kappaC(alpha):eta2-CH = CH2)Pt(C6F5)2] 4 or (mu-hydride)(mu-alkynyl) [cis,cis (PPh3)2Pt(mu-H)(mu-1kappaC(alpha):eta2-C [triple bond]CR)Pt(C6F5)2] (R = SiMe3 5, Bu(t) 6) compounds, respectively. The monitoring of these reactions by NMR spectroscopy has allowed us to detect several intermediates, and to propose a mechanism for the C-H bond activation. In addition, the structures of the (muo hydride)(mu-alkynyl) complex 5 and the unprecedented (mu-hydride)(mu-vinyl) derivative 4 have been obtained by X-ray crystallographic analyses. PMID- 17844661 TI - Layered microporous tin(IV) bisphosphonates. AB - This article reports the hydrothermal synthesis and characterization of two new series of porous tin(IV) phosphonophenoxyphenylphosphonates with controlled pore size distributions, using as precursor the 4-(4'-phosphonophenoxy)phenyl phosphonic acid, [H2O3P-C6H4]2-O. Supermicroporous solids (S(BET), 300-400 m2 g( 1)) were obtained employing n-alcohol (C1-C6)-water mixtures (solvents ratio 1 : 1), in the presence of hydrofluoric acid. X-Ray powder diffraction shows that these compounds are semi-crystalline and the local environments around the phosphorus and tin elements have been studied by 31P and 119Sn MAS-NMR spectroscopy, respectively. The microstructure (particle sizes and shapes) of these phosphonates has been analyzed by scanning and transmission electron microscopy. This study shows that the microstructures of single-ligand (for instance tin(IV) phenylphosphonate) and cross-linked tin(IV) bisphosphonates are different. Tin(IV) phenylphosphonate crystallizes as micron-sized spheres, theta approximately 1-2 microm, formed by the aggregation of nanospheres, whereas tin(IV) bisphosphonates crystallize as microparticles larger than 20 microm. The textural properties of these porous solids were characterized by N2 and CO2 sorption isotherms. The key result of this work is that maxima of pore size distributions smoothly shift from 12 to 16 angstroms upon increasing the chain length of the alcohol. The microporosity of tin(IV) bisphosphonates is compatible with a double role played by the phosphonate groups acting as a pillar between adjacent layers and as a component of the hybrid organic-inorganic layers. PMID- 17844662 TI - Synthesis, magnetic behaviour, and X-ray structures of dinuclear copper complexes with multiple bridges. Efficient and selective catalysts for polymerization of 2,6-dimethylphenol. AB - The use of a potentially tridentate mono-anionic bridging ligand, 1,3-bis(3,5 dimethylpyrazol-1-yl)-propan-2-ol (bdmpp-H), in assembling new dimeric copper complexes with interesting magnetic properties has been investigated. The reaction of copper hydroxide or copper acetate with phenyl phosphinic acid or diphenyl phosphinic acid in the presence of bdmpp-H produces the dinuclear complexes [Cu(bdmpp)(ppi)]2 (1) and [Cu(bdmpp)(dppi-H)]2(dppi)2 (2) (ppi-H = phenylphosphinic acid: dppi-H = diphenylphosphinic acid), respectively. The products have been characterized with the help of analytical, thermal, and spectroscopic (IR, UV-vis, and EPR) techniques. Single crystal X-ray diffraction studies of 1 and 2 reveal that the two bdmpp ligands hold together the dimeric copper unit in each complex through mu-O alkoxide and the pyrazolyl nitrogen ligating centers. Two phenyl phosphinate ligands additionally bridge the dicopper core in 1 to result in octahedral coordination geometry around each metal ion. The diphenyl phosphinic acid acts as a terminal ligand in 2, and thus completes a square pyramidal geometry around each copper ion. Both complexes show a very short Cu...Cu separation (3.001 and 3.065 angstroms for 1 and 2, respectively). The investigation of the magnetic properties reveals the efficiency of the double alkoxide bridge between the two paramagnetic copper ions to mediate strong antiferromagnetic interactions [J/k(B) = -620(5) K (-431(4) cm(-1)) and -685(5) K (-476(4) cm(-1)) for 1 and 2, respectively]. Compounds 1 and 2, along with a few other copper phosphate complexes, were tested as catalysts for the oxidative polymerization of 2,6-dimethylphenol; 1 and 2 were found to be efficient catalysts with an increased selectivity for the formation of the polyphenylene ether. However a related mononuclear octahedral copper complex [Cu(imz)4(dtbp)2] (dtbp-H = di-tert-butylphosphate) was found to be more efficient. PMID- 17844663 TI - Non-innocent behaviour of ancillary and bridging ligands in homovalent and mixed valent ruthenium complexes [A2Ru(mu-L)RuA2]n, A = 2,4-pentanedionato or 2 phenylazopyridine, L(2-) = 2,5-bis(2-oxidophenyl)pyrazine. AB - Structurally characterised 2,5-bis(2-hydroxyphenyl)pyrazine (H2L) can be partially or fully deprotonated to form the complexes [(acac)2Ru(mu-L)Ru(acac)2], [1], acac = acetylacetonato = 2,4-pentanedionato, [(pap)2Ru(mu L)Ru(pap)2](ClO4)2, [2](ClO4)2, pap = 2-phenylazopyridine, or [(pap)2Ru(HL)](ClO4), [3](ClO4). Several reversible oxidation and reduction processes were observed in each case and were analysed with respect to oxidation state alternatives through EPR and UV-VIS-NIR spectroelectrochemistry. In relation to previously reported compounds with 2,2'-bipyridine as ancillary ligands the complex redox system [1]n is distinguished by a preference for metal based electron transfer whereas the systems [2]n and [3]n favour an invariant Ru(II) state. Accordingly, the paramagnetic forms of [1]n, n = -, 0, +, exhibit metal-centred spin whereas the odd-electron intermediates [2]+, [2](3+) and [3] show radical-type EPR spectra. A comparison with analogous complexes involving the 3,6-bis(2-oxidophenyl)-1,2,4,5-tetrazine reveals the diminished pi acceptor capability of the pyrazine-containing bridge. PMID- 17844664 TI - Three-component coordination networks based on [Ru(phen)(CN)4(2-) anions, near infrared luminescent lanthanide(III) cations, and ancillary oligopyridine ligands: structures and photophysical properties. AB - A series of cyanide-bridged coordination networks has been prepared which contain [Ru(phen)(CN)4](2-) anions, Ln(III) cations, and additional oligopyridine ligands (1,10-phenanthroline, 2,2':6',2'''-terpyridine or 2,2'-bipyrimidine) which coordinate to the Ln(III) centres. Five structural types have been identified and examples of each type of structure are described: these are hexanuclear Ru4Ln2 clusters; two-dimensional Ru-Ln sheets with a honeycomb pattern of edge-linked Ru6Ln6 hexagons; one-dimensional chains consisting of two parallel cross-linked strands in a ladder-like arrangement; simple single-stranded chains of alternating Ru/Ln components; and a one-dimensional 'chain of squares' in which Ru2Ln2 squares are linked by bipyrimidine bridging ligands which connect to the Ln(III) corners of adjacent squares in the sequence. The 3MLCT luminescence characteristic of the [Ru(phen)(CN)4](2-) units is quenched in those networks containing Ln(III) which have low-lying near-infrared luminescent f-f states [Pr(III), Nd(III), Er(III), Yb(III)], with sensitised Ln(III)-based near-IR luminescence generated by d --> f energy-transfer. The rate of d --> f energy transfer, and hence the degree of quenching of the 3MLCT luminescence from the [Ru(phen)(CN)4](2-) units, depends on the availability of f-f levels of an appropriate energy on the Ln(III) centre, with Nd(III) (with a high density of low-lying f-f states) being the most effective energy-acceptor and Yb(III) (with a single low-lying f-f state) being the least effective. Rates of d --> f energy transfer to different Ln(III) centres could be determined from both the residual (partially quenched) lifetimes of the 3MLCT luminescence, and--in the case of the Yb(III) networks--by a rise-time for the sensitised near-IR luminescence. The presence of the 'blocking' polypyridyl ligands, which reduced the number of cyanide and water ligands that would otherwise coordinate to the Ln(III) centres, resulted in increases in the Ln(III)-based emission lifetimes compared to networks where these blocking ligands were not used. PMID- 17844665 TI - Dicopper(II) complexes of a new di-para-xylyldioxatetraazamacrocycle and cascade species with dicarboxylate anions: thermodynamics and structural properties. AB - The new dioxatetraazamacrocycle (L1) was synthesized by a 2 + 2 condensation and characterized. Stability constants of its copper(II) complexes were determined by spectrophotometry in DMSO at 298.2 K in 0.10 mol dm(-3) KClO4. Mainly dinuclear complexes are formed and the presence of mononuclear species is dependent on the counterion (Cl- or ClO4-). The association constants of the dinuclear copper(II) complexes with dicarboxylate anions [oxalate (oxa(2-)), malonate (mal(2-)), succinate (suc(2-)), and glutarate (glu(2-))] were also determined by spectrophotometry at 298.2 K in DMSO, and it was found that values decrease with an increase of the alkyl chain between the carboxylate groups. X-Band EPR spectra of the dicopper(II) complexes and of their cascade species in frozen DMSO exhibit dipole-dipole coupling, and their simulation, together with their UV-vis spectra, showed that the copper centres of the complexes in solution had square pyramidal geometries though with different distortions. From the experimental data, it was also possible to predict the Cu...Cu distances, the minimum being found at 6.4 angstroms for the Cu2L1Cl4 complex and then successively this distance slightly increases when the chloride anions are replaced by dicarboxylate anions, from 6.6 angstroms for oxa(2-) to 7.8 angstroms for glu(2-). The crystal structures of the dinuclear copper cascade species with oxa(-2) and suc(2-) were determined and showed one anion bridging both copper centres and Cu...Cu distances of 5.485(7) angstroms and 6.442(8) angstroms, respectively. PMID- 17844666 TI - Synthesis and structural studies of germyl and germyl/stannyl substituted tungstenocenes. AB - One-pot reactions of [WCp2(H)2] and [WCp2(H)(SnMe3)] with "BuLi followed by an equivalent of GeMe2Cl2 afford mono(germyl) substituted tungstenocenes [WCp2(H)(GeMe2Cl)] (1) and [WCp2(SnMe3)(GeMe2Cl)] (7). Reactions of the products with tin halides in the presence NEt3 afford the mixed complexes [WCp2(SnR2X)(GeMe2Y)] (X, Y = Cl, Br, R = Me, Et), which were further converted to moderately stable compounds [WCp2(SnR2H)(GeMe2H)] (R = Me (10), Et (11)). A number of asymmetric mono(halo)-substituted germyl/stannyl tungstenocenes [WCp2(SnMe2X)(GeMe2H)] (X = Cl (12), Br (13)) and [WCp2(SnEt2Y)(GeMe2H)] (Y = Br (14), I (15)) were prepared by selective halogenation of the Sn-H bond in 10 and 11. X-Ray studies of [WCp2(H)(GeMe2Cl)] (1), [WCp2(SnEt2Br)(GeMe2Cl)] (4), and [WCp2(SnEt2Br)(GeMe2H)] (14) established classical structures of these compounds. X-Ray study of complex [WCp2(SnMeCl)(GeMe2Cl)] (3) revealed the presence of interligand Ge-Cl...Sn-Cl interactions in a highly Ge/Sn disordered structure. Analyses of molecular parameters of 1, 4, and 14 suggest the presence of a negative hyperconjugation between metal lone pairs and the sigma*-orbital of the E-X bond, which is stronger in bromo substituted complexes in comparison with chloro substituted ones. PMID- 17844667 TI - New insights into the thermal stability of Mn12 clusters: the case of complex [Mn12O12(O2CC[triple bond]-CH)16(H2O)4] x 3H2O and its thermolysis derived [Mn3(O2CC[triple bond]CH)6(H2O)4] x 2H2O complex. AB - Two novel Mn12 derivatives [Mn12O12(O2CC[triple bond]CH)16(H2O)4] x 3H2O (1) and [Mn12(O2CC[triple bond]CC6H5)16(H2O)4] x 3H2O (2) have been prepared and characterized. Magnetic measurements confirm that both function as single molecule magnets (SMM), showing frequency-dependent out-of-phase AC susceptibility signals and magnetization hysteresis curves. Thermal stability studies of both complexes were first conducted in the solid state. While complex 1 undergoes a sudden exothermal decomposition at T(onset) = 118 degrees C, complex 2 exhibits a higher stability. Thermolysis reaction of 1 was hence assessed in solution to yield dark red crystals of a two-dimensional Mn(II)-based co-ordination polymer [Mn3(O2CC[triple bond]CH)6(H2O)4] x 2H2O (3), which corresponds to an extended sheet-like structure that crystallizes in the monoclinic space group P2(1)/n; a = 9.2800(2) angstroms, b = 9.4132(2) angstroms, c = 14.9675(3) angstroms, beta = 99.630(1) degrees, and Z = 2. Finally, the magnetic properties of complex 3 have been studied on an oriented single crystal over two different orientations of the reciprocal vector versus the external field. PMID- 17844668 TI - Ca(2+)/vacancies and O2-/F- ordering in new oxyfluoride pyrochlores Li(2x)Ca1.5-x square 0.5-xM2O6F (M = Nb,Ta) for 0 < or = x < or = 0.5. AB - New oxyfluorides Li(2x)Ca(1.5-x) square (0.5-x)M2O6F (M = Nb, Ta), belonging to the cubic pyrochlore structural type (Z = 8, a approximately 10.5 angstroms), were synthesized by solid state reaction for 0 < or = x < or = 0.5. XRD data allowed us to determine their structures from single crystals for the two alpha and beta-Ca(1.5) square (0.5)Nb2O6F forms and from powder samples for the others. This characterisation was completed by TEM and solid state 19F NMR experiments. For the Ca(1.5) square (0.5)M2O6F (x = 0) pyrochlore phases, the presence of a double ordering phenomenon is demonstrated, involving on one hand the Ca(2+) ions and the vacancies and on the other hand the oxide and the fluoride anions which are strictly located in the 8b sites of the Fd3m aristotype space group. The Ca(2+) ions/vacancies ordering leads to a reversible phase transition, a (P4(3)32) <--> beta (Fd3m). The 19F NMR study strongly suggests that, in the beta phases, the fluoride ions are only on average at the centre of the Ca3 square tetrahedron. It shows that slightly different Ca-F distances occuring in alpha Ca(1.5) square (0.5)Nb2O6F may be related to a more difficult thermal ionic and vacancies diffusion process than in the tantalate compound. This may explain the hysteresis phenomenon presented by the phase transition. A solid solution Li(2x)Ca(1.5-x) square (0.5-x) Ta2O6F (0 < or = x < or = 0.5) was prepared and the order-disorder phase transition observed for Ca(1.5) square (0.5)M2MO6F compounds disappears for all the other compositions where less or no more vacancies exist in the 16d sites. In the LiCaM2O6F compounds, the 19F NMR study allows us to determine the Ca(2+) and Li+ ions distributions around the fluoride ions and shows that the [FLi2Ca2] environment is clearly favoured. PMID- 17844669 TI - Clinic needs your help. PMID- 17844670 TI - Getting answers to our Blue Dental/DenteMax questions. PMID- 17844671 TI - HIPAA won't stop officials from obtaining patient records. PMID- 17844672 TI - Resistance to change is the main issue. PMID- 17844673 TI - Personal growth begins with a flush! PMID- 17844674 TI - Effective time management tips for the dental executive. PMID- 17844675 TI - Dental fraud in the 21st century. PMID- 17844676 TI - Women and heart disease: do you know the risks? PMID- 17844677 TI - Antimicrobial mouthrinses: literature review and clinical application. PMID- 17844678 TI - The MDA's new policy on non-accredited dental assistant training programs. PMID- 17844679 TI - [Missed chance for a basic reform of nursing insurance?]. PMID- 17844680 TI - [Practical dealing with colored light in neonatal intensive care]. PMID- 17844681 TI - [Rituals in pediatric nursing -- possibilities and limitations]. PMID- 17844682 TI - [Family-oriented care of children with lip-palate-jaw clefts]. PMID- 17844684 TI - [Tested UV-protective clothing for children. Thus the summer is fun!]. PMID- 17844683 TI - [Tick bites, Lyme disease and early summer meningoencephalitis. Current indications concerning infection risks, prevention and therapy]. PMID- 17844685 TI - [Hygienic requirements in the milk kitchen]. PMID- 17844686 TI - [Sex identity disorders in children and adolescents]. PMID- 17844687 TI - [Small bands of the tongue -- cut or not cut? Pathophysiological bases and recommendations]. PMID- 17844688 TI - [Abbott proposes in Europe and the U.S.A. the approval of Humira (adalimumab) for therapy of juvenile idiopathic arthritis. Pediatric clinical trial shows very promising results in juvenile rheumatoid arthritis]. PMID- 17844689 TI - [Sudden death in children (SIDS) -- ultrasound screening not to be advised!]. PMID- 17844690 TI - India--diabetes capital of the world: now heading towards hypertension. PMID- 17844691 TI - Prevalence, awareness and control of hypertension in Chennai--The Chennai Urban Rural Epidemiology Study (CURES-52). AB - OBJECTIVE: To study the prevalence, awareness and control of hypertension in Chennai representing Urban South India. METHODS: The Chennai Urban Rural Epidemiology Study (CURES) is one of the largest epidemiological studies on diabetes carried out in India, where 26,001 individuals aged > or = 20 years were screened using systematic random sampling method. Every tenth subject recruited in Phase 1 of CURES was requested to participate in Phase 3 of CURES and the response rate was 2,350/26,001 or 90.4%. An oral glucose tolerance test was performed in all individuals except self-reported diabetic subjects. Anthropometric measurements and lipid estimations were done in all subjects. Hypertension was diagnosed in all subjects who were on drug treatment for hypertension or if the blood pressure > or = 140/90 mmHg. RESULTS: Hypertension was present in 20% [men:23.2% vs. women:17.1%, p<0.001] of the study population. Isolated systolic hypertension (Systolic BP > or = 140 and Diastolic BP<90 mmHg) was present in 6.6% while isolated diastolic hypertension (DBP > or = 90 and SBP<140 mmHg) was present in 4.2% of the population. Among the elderly population (aged > or = 60 years), 25.2% had isolated systolic hypertension. Age, body mass index, smoking, serum cholesterol and triglycerides were found to be strongly associated with hypertension. Among the total hypertensive subjects, only 32.8% were aware of their blood pressure, of these, 70.8% were under treatment and 45.9% had their blood pressure under control. CONCLUSION: Hypertension was present in one-fifth of this urban south Indian population and isolated systolic hypertension was more common among elderly population. Majority of hypertensive subjects still remain undetected and the control of hypertension is also inadequate. This calls for urgent prevention and control measures for hypertension. PMID- 17844692 TI - Induction of long-term glycemic control in type 2 diabetic patients using pioglitazone and metformin combination. AB - AIMS AND OBJECTIVE: To study the effects of pioglitazone and metformin combination in type 2 diabetics in achieving long-term optimal glycemic control. METHODS AND MATERIALS: Patients whose duration of type 2 diabetes was less than 24 months were selected for the study. 373 such patients meeting the selection criteria were included in the study and were started on triple drug combination therapy. RESULTS: Three hundred seventy three (183 females and 190 males) patients were initiated on a triple drug combination of gliclazide 80 mg, tid, metformin 500 mg tid and pioglitazone 30 mg od. Once controlled, the doses of gliclazide were reduced if the blood glucose levels decreased. Those patients whose plasma glucose remained in the normal range for more than 6 months without the use of a sulphonylurea were considered to be in pharmacological remission. 48 patients were lost to follow up. At the beginning of the study the pre treatment biochemical parameters in these 325 diabetic patients at the time of enrolment were: average FBG of 209.44+/-73.82 mg/dl, PLBG 294.96+/-107.58 mg/dl, and HbA(1c) 11.21+/-3.85. The post treatment glycemic parameters were: FBG was 124.38+/-40.48 mg/dl (p < 0.0001), and PLBG 162.32+/-54.33 mg/dl (p < 0.001), average glycosylated hemoglobin was 6.45+/-2.17 (p < 0.001). After using the triple drug combination pharmacological remission was achieved in 36.3 percent i.e. 118 (60 males and 58 females) patients. The average time required for achieving remission was 4 (+/-3.3) months in males and 5 (+/-4.02) months in females. 118 patients were maintained remission after 2 years of follow up. The average duration of remission is 27 (+/-2.66) months. There was an average weight gain of 2.56 +/- 1.32 kg in both the groups of patients in remission and those who could not achieve remission. CONCLUSIONS: In this study we have found that we could achieve long term glycemic control 'pharmacological remission' in 118 of the 325 patients i.e.36% of type 2 diabetic patients. Insulin sensitizers like pioglitazone along with metformin may induce long-term glycemic control in type 2 diabetic patients. PMID- 17844693 TI - Trial of low molecular weight heparin in the treatment of viper bites. AB - AIM OF THE STUDY: To study the efficacy of low molecular weight heparin (LMWH) in the treatment of viper envenomation to combat the haematotoxicity and disseminated intravascular coagulation (DIC). METHODOLOGY: Eighty patients with viper bite and incoagulable blood were randomized into two groups of 40 each. One group (Test group) received LMWH, in addition to the antisnake venom (ASV) and other routine measures received by the other group (Control group). Efficacy was assessed by monitoring the bleeding time (BT), whole blood clotting time (CT), prothrombin time (PT), platelet count, fibrinogen, blood urea (BU), serum creatinine, development of complications and overall outcome. RESULTS: LMWH group showed favourable outcome in all the parameters except in the incidence of renal failure which was reversible in the majority of the cases. However the differences between the two groups were statistically not significant. CONCLUSION: LMW heparin seems to have a beneficial role in the treatment of viper bites, but this needs to be confirmed by a larger trial using a higher dose of heparin. PMID- 17844694 TI - Traditional journal club: a continuing problem. AB - OBJECTIVE: To evaluate the pattern, motivation and facilities for choosing journal club topics by residents in two medical institutions in India. METHOD: A self-appraisal questionnaire was used to compare motivation for choice of topics, availability of infrastructure, sites and type of articles accessed and formal training in computer based literature search in two medical institutions- a postgraduate institute (PGI) and medical college (MC) which provided mainly specialty and superspecialty training respectively. RESULTS: One hundred and fifty five out of two hundred and fifty five residents responded to the questionnaire. Super-specialty training was pursued by 58 and specialty training by 97 residents. The residents in PGI more frequently selected journal articles which they considered good and in MC, faculty guidance determined the choice of journal club topics. The super-specialty residents, however, more frequently selected patient management related topics compared to specialty residents. MEDLINE and MD Consult were more frequently accessed by PGI residents where infrastructure and training in literature search were superior to MC. CONCLUSION: In both the institutions surveyed, journal clubs were of traditional type. Better infrastructure and training at PGI were not reflected in quality of journal club. Successful journal club should focus on current, real patient's problem of most interest to the group. PMID- 17844695 TI - Quadricuspid aortic valve. PMID- 17844696 TI - Chronic gout and osteoarthritis. PMID- 17844697 TI - Management of early rheumatoid arthritis. AB - Rheumatoid arthritis is a treatable cause of disability. The benefits of disease modifying anti-rheumatic drug therapy (DMARD) have been established, and current best practice is to commence it as early as possible during the course of RA. Equally, important is to monitor treatment effects, and adjust therapy accordingly. Because remission, the current goal of management, is difficult to achieve with single DMARD therapy, there has been increased interest with early use of combination DMARD therapy as well as biological therapy. Most patients require symptom-relieving treatments as well but it is best to limit exposure to non-steroidal anti-inflammatory drugs and systemic corticosteroids to minimise cardiovascular risk. Patients also benefit from input of other members of the multidisciplinary team, and measures designed to improve cardiovascular health. Further studies would hopefully help to improve therapeutic strategies, and achieve remission and prevent disability. PMID- 17844698 TI - Idiopathic pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) is being more frequently diagnosed in India, due to its increased awareness, better availability of computed tomography (CT) and fiberoptic bronchoscopy. IPF has the histological appearance of usual interstitial pneumonia (UIP) on surgical lung biopsy. Recent research has given a new insight into the etiology of the disease. Clinical criteria have been specified for presumptive diagnosis of IPF and distinguishing IPF from other conditions. The conventional therapy has been steroids and immunosuppressive agents. But only a minority of patients respond to such a therapy. Immunomodulators (interferon Y1b), antioxidants (Acetyl cysteine) and antifibrotic agents (like pirfenidone) are being studied as novel therapies in this, otherwise, fatal condition. Lung transplantation is the only hope for those patients who show progressive deterioration on medical treatment. Living-donor lobar lung transplantation has been developed as a procedure for patients considered too ill to await cadaveric lung transplantation. PMID- 17844699 TI - Paget-Schroetter syndrome. AB - A case of primary upper-extremity deep vein thrombosis (UEDVT) or Paget Schroetter syndrome is reported. It is effort thrombosis usually affecting young healthy individuals and is a rare condition. Our patient was an elderly male with history of exertion using the left upper limb. He responded to limb elevation and anticoagulation. No other cause for thrombosis was found. PMID- 17844700 TI - Squamous cell carcinoma arising from primary retroperitoneal mature teratoma. AB - A 65 year old postmenopausal female presented with left sided abdominal pain. Sonogram revealed an intra-abdominal 7.4 x 5.7 cm heterogenous mass. On laparotomy, approximately 10 X 10 cm mesenteric mass was seen adherent to the descending colon. Multiple omental tumor deposits were also noted. Gross examination showed solid and cystic tumor with sebaceous material admixed with hair. Histopathology showed mature cystic teratoma with a spectrum of well to poorly differentiated squamous cell carcinoma with omental metastasis. PMID- 17844701 TI - Diabetic ketosis as a presenting feature of acromegaly. AB - Secondary diabetes mellitus is known to occur in acromegaly due to insulin resistance caused by growth hormone excess. However diabetes in acromegaly usually does not lead to ketosis. We describe here a case of acromegaly who presented in diabetes ketosis, which is unusual. PMID- 17844702 TI - Medical philately (medical theme on stamps). Telemedicine. PMID- 17844703 TI - A new strategy of drug treatment in NSAID--unresponsive ankylosing spondylitis. PMID- 17844704 TI - Incidence of renal artery stenosis in patients undergoing coronary angiography. PMID- 17844705 TI - Clinical use of evidence-based medicine: studies used to assess harm. AB - Studies of harm are often carried out in cohort or case-controlled studies. We reviewed a prospective cohort study by Halton et al that assessed increased cardiovascular events in women on a low carbohydrate diet. This study did not show an increase in cardiovascular events. However, the diet assessment was very subjective, and the control group was dissimilar. The fact that these women were not trying to lose weight may have also affected the results. The randomized controlled trial by Trudy et al compared weight loss in 4 different commercially available diets and revealed similar weight loss in all 4 groups. Cholesterol levels did not increase in the Atkins group and systolic blood pressure decreased, although not significantly. Our patient will likely lose weight if she is able to continue with any of these diets. Although the evidence evaluating increased cardiovascular events in patients on the Atkins diet is not strong, the available evidence does not show that the Atkins diet increases this risk. PMID- 17844706 TI - Residents are right, and I am confused: a short story. PMID- 17844707 TI - Endemic human mosquito-borne disease in Wisconsin residents, 2002-2006. AB - INTRODUCTION: West Nile virus (WNV) and La Crosse virus (LAC) are the primary mosquito-borne arboviruses associated with human disease in Wisconsin. We examined WNV and LAC human illness surveillance data collected during 2002 through 2006. METHODS: ELISA-based tests developed by the Centers for Disease Control and Prevention (CDC) were used to detect acute WNV and LAC infection in patient sera or cerebral spinal fluid. Public health personnel conducted patient follow-up using standard arbovirus reporting forms. CDC/Council of State and Territorial Epidemiologists definitions were used to determine cases. RESULTS: From 2002 through 2006, 114 confirmed human cases of WNV illness were reported in Wisconsin residents; 82% of illness onsets occurred during August or September. Median age of WNV case patients was 51 years, 49% reported neuroinvasive disease, 56% were hospitalized, and 7 cases were fatal. Confirmed LAC illnesses declined from a high of 27 cases during 2003 to a low of 3 cases during 2005 and 2006. Most LAC illnesses occurred in residents of Western Wisconsin; median age of LAC cases was 9 years. Mean annual incidences of reported confirmed WNV illnesses calculated for high, medium, and low population density groupings were very similar (range: 0.40-0.46 cases/100,000 population). CONCLUSIONS: Humans are at risk for mosquito-borne diseases in Wisconsin. Protection and prevention measures are important statewide, especially during July through September when the risk is greatest. PMID- 17844708 TI - Epidemiologic features of human babesiosis in Wisconsin, 1996-2005. AB - OBJECTIVE: To characterize epidemiologic, clinical, and laboratory features of babesiosis occurring in Wisconsin residents. DESIGN: Conduct a review of all cases of babesiosis reported to the Wisconsin Division of Public Health with onsets during 1996-2005. For case patients with onsets during 2004, pertinent medical records were reviewed and patient interviews were performed. INTERVENTIONS: Increase awareness of the occurrence and recent trends and facilitate prompt, appropriate diagnosis and treatment of babesiosis. Increase awareness among clinicians of the Infectious Diseases Society of America guidelines for the management of babesiosis, Lyme disease, and human granulocytic anaplasmosis. MAIN OUTCOME MEASURES: The study represents an analysis of data received through passive surveillance of a disease that is officially reportable to the Wisconsin Division of Public Health. Other than the description of the occurrence of babesiosis among Wisconsin residents, there were no planned outcome measures. RESULTS: Of the 32 cases of babesiosis reported to the DPH during the study interval, 23 (72%) occurred during 2004 and 2005. The majority of cases occurred in northwestern and west-central Wisconsin. At least 6 patients were co infected with other tick-borne pathogens. Anemia, thrombocytopenia, and elevation of liver transaminase levels were the most notable laboratory abnormalities among case patients. CONCLUSIONS: The apparent increased incidence in babesiosis among Wisconsin residents should impact clinicians' workups for acute febrile illness with known tick exposure, especially in northwest and west central Wisconsin. Babesiosis should now also be considered in patients diagnosed with Lyme disease who have marked constitutional symptoms, especially those with anemia or thrombocytopenia. PMID- 17844709 TI - Improving cancer incidence estimates for American Indians in Wisconsin. AB - OBJECTIVES: The purpose of this study was to improve the measurement of cancer incidence among American Indians in Wisconsin and compare incidence rates with state and national incidence rates. METHODS: The Wisconsin Cancer Reporting System (WCRS) entered into a data linkage project with CDC and the Indian Health Service (IHS) to improve classification of American Indian cancer cases in Wisconsin. WCRS data were linked to IHS patient registration files to identify American Indian cases that were misclassified as a non-Indian race for the years 1998-2002. American Indian age-adjusted rates and rate ratios for major cancer sites were compared before and after the linkage, and with statewide and national rates. RESULTS: The age-adjusted incidence rate for all cancer among American Indians increased from the pre-linkage rate of 386.3 per 100,000 to the post linkage rate of 471.7 per 100,000, a statistically significant increase. The post linkage rate was over twice the comparable Surveillance Epidemiology and End Results (SEER) national rate among American Indians at 233.6 per 100,000. Post linkage American Indian incidence rates for male colorectal and female lung cancers were higher than those for the state average. CONCLUSIONS: In contrast to earlier data, the linkage results show that American Indians had similar cancer incidence compared to the general population in Wisconsin, and over twice as high as national SEER American Indian rates. Post-linkage rates resulted in more accurate site-specific and geographically focused cancer incidence rates to help target the national and state priorities of addressing disparities among American Indians. PMID- 17844710 TI - Implementing CAP guidelines: impediments and opportunities. AB - CONTEXT: The implementation of guidelines for treatment of Community-Acquired Pneumonia (CAP) has been proposed as a quality improvement and cost-saving strategy, though the effectiveness of several recommendations has yet to be confirmed through clinical trials. We sought to analyze the development and implementation of guidelines at our hospital, and to identify particular successes and impediments. EVIDENCE ACQUISITION: Date sources included the Web sites of the Joint Commission on Accreditation of Healthcare Organizations, the Infectious Disease Society of America, and the American Thoracic Society. References from their guidelines were reviewed, and further citations were obtained using Ovid software to search for references within the last 15 years using "pneumonia guideline," "pneumococcal vaccination," and other relevant search terms. Our own hospital data was compiled, analyzed, and presented using Excel software. EVIDENCE SYNTHESIS: Significant improvement was seen during the 2 year study period when CAP guidelines were implemented at our hospital. However, we also identified several impediments, which will require further attention to achieve our quality improvement goals. CONCLUSIONS: Our implementation of CAP guidelines was challenging but overall instructive and contributory to patient care. We review further areas for improvement. PMID- 17844711 TI - Physician beliefs and practices regarding the use of hepatitis A vaccine. AB - BACKGROUND: In 1999, the Centers for Disease Control and Prevention recommended routine vaccination of children against hepatitis A in states, counties, and communities with rates twice the national average or greater. Milwaukee is such a community. OBJECTIVES: To assess physician knowledge, beliefs, and practices regarding hepatitis A disease and hepatitis A vaccine recommendations in Milwaukee. METHODS: A cross-sectional study of 291 Milwaukee pediatricians and family physicians using a self-administered questionnaire. RESULTS: The response rate was 46%. Of physicians responding, 88% were aware that hepatitis A vaccine was recommended for all children in Milwaukee >2 years of age; 61% believed hepatitis A was a significant health problem, with a significant difference between pediatricians and family physicians (74% versus 43%); and 65% stated they offered the vaccine "almost always" or "most of the time" to children between the ages of 2 and 19 years. CONCLUSIONS: More physician education is needed regarding the public health impact of hepatitis A and the value of the vaccine. PMID- 17844712 TI - Competency-based physician education, recertification, and licensure. AB - Discussions about competency-based education are occurring at all levels of medical education: medical school, residency, and continuing education. Competencies are also an important aspect of certification and are likely to be a part of physician licensure. The 6 General Competencies from the Accreditation Council for Graduate Medical Education (ACGME)--patient care, medical knowledge, practice-based learning and improvement, professionalism, interpersonal and communication skills, and systems-based practice-are firmly established in residency education and are rapidly infusing and changing both medical student and continuing medical education. As physicians must continuously learn and maintain certification throughout their careers, it is essential to understand what competency-based education is and its implications. This article provides an overview of the meaning, history, and evolution of competency-based education and emerging approaches to assessing competence across the continuum of physician education. The discussion asserts that a new view of education is required in which individual competence in key areas is synergistically taught, learned, and assessed. PMID- 17844714 TI - Primary mediastinal embryonal carcinoma masquerading as chronic pancreatitis. AB - Primary mediastinal embryonal cell carcinomas are aggressive tumors commonly presenting between the ages of 20-50 years with pulmonary symptoms (e.g., cough, chest pain, and hemoptysis), as well as extrapulmonary symptoms due to pressure on adjacent structures. Here we describe a 72-year-old man who remained undiagnosed for a prolonged period of time because of intractable epigastric pain. The patient was thought to have chronic pancreatitis for several months until a chest computed tomography scan demonstrated the mass. This case exemplifies that embryonal cell carcinoma may present in older age groups. It also illustrates the importance of including mediastinal tumors in the differential diagnosis of chronic epigastric pain and the need for further investigations to identify these tumors. PMID- 17844713 TI - Management strategies for ST-elevation myocardial infarction in the emergency department. AB - Review of existing evidence supports that percutaneous coronary intervention (PCI) is superior to thrombolytic therapy in patients with acute myocardial infarction. If, however, a dedicated intervention team is not available onsite, transfer to another facility should be considered if reperfusion could be achieved within 90 minutes. If that goal cannot be achieved within 120 minutes, thrombolytic therapy should be administered with a planned transfer to a facility with PCI capability. In patients with cardiogenic shock or recurrence of anginal chest pain, PCI should be immediately considered. The value of administering full or modified dose thrombolytic therapy and then transferring for immediate PCI has not been demonstrated yet. Development of dedicated protocols for management of ST-elevation myocardial infarction developed by a community-based emergency medical service, emergency department, and cardiovascular service is highly recommended. PMID- 17844715 TI - The DEA proposes schedule II substance rule. PMID- 17844716 TI - Academic campuses extend the school's reach to all corners of the state. PMID- 17844717 TI - Roth IRA opportunity expanded in 2010. PMID- 17844718 TI - Medicare physician quality reporting initiative. PMID- 17844719 TI - Balancing individual and communal needs: plague and public health in early modern Seville. AB - This article offers a reexamination of the impact of bubonic plague epidemics, using sixteenth-century Seville as a case study. It argues that municipal health officials did not simply shut down the city in times of plague, but successfully negotiated a balance between medical concerns and economic interests. While officials enacted a traditional regimen of public health measures, such as travel bans and quarantines, they also maintained open lines of communication with residents and continually allowed individual exemptions from plague restrictions. Such exemptions empowered residents, allowed trade to continue, and dissipated popular resistance. Redefining public health to more broadly include the overall well-being of the community, this article finds that Seville's health officials successfully maintained public health by balancing the needs of the individual and the community. PMID- 17844720 TI - Parsimony, power, and prescriptive legislation: the politics of pauper lunacy in Northamptonshire, 1845-1876. AB - The Northampton General Lunatic Asylum opened in 1836 and was funded through local subscriptions. Unlike many other subscription asylums, it did not become a county asylum after the 1845 Lunacy Acts, but was registered as a charitable hospital. This article explores the dynamics that resulted in the Northamptonshire authorities' successfully evading their responsibility to build a county asylum. The loopholes in the supposedly mandatory legislation are examined, with the implications this had for the relationship between the Commissioners in Lunacy and the NGLA governors, as well as the conflict between the local magistrates and the NGLA governors that eventually forced Northamptonshire to conform and build its own specific county asylum in 1876. PMID- 17844721 TI - Crafting medical history: revisiting the "definitive" account of Franklin D. Roosevelt's terminal illness. AB - While revisionist historians have challenged many standard interpretations of events in the presidency of Franklin D. Roosevelt, one account has remained virtually unscathed: an article about Roosevelt's terminal illness and death written by one of his physicians, Howard G. Bruenn. Yet this article, like all historical documents, was not "objective" but rather a reflection of social and political forces--both from the 1940s, when Roosevelt became ill, and from 1970, when Bruenn's piece was published. This essay argues that Bruenn, the Roosevelt family, and the historian James MacGregor Burns worked together to craft a document that told the story of Roosevelt's decline with a predictable trajectory. PMID- 17844722 TI - Vikings against tuberculosis: the International Tuberculosis Campaign in India, 1948-1951. AB - Between 1947 and 1951 the Scandinavian-led International Tuberculosis Campaign tested more than 37 million children and adolescents for tuberculosis, and vaccinated more than 16 million with BCG vaccine. The campaign was an early example of an international health program, and it was generally seen as the largest medical campaign to date. It was born, however, as a Danish effort to create goodwill in war-ravaged Europe, and was extended outside Europe only because UNICEF in 1948 unexpectedly donated US $2 million specifically for BCG vaccination in areas outside Europe. As the campaign transformed from postwar relief to an international health program it was forced to make adaptations to different demographic, social, and cultural contexts. This created a tension between a scientific ideal of uniformity, on the one hand, and pragmatic flexibility on the other. Looking at the campaign in India, which was the most important non-European country in the campaign, this article analyzes three issues in more detail: the development of a simplified vaccination technique; the employment of lay-vaccinators; and whether the campaign in India was conceived as a short-term demonstration or a more extensive mass-vaccination effort. PMID- 17844723 TI - The use of opioid analgesia in end-stage renal disease patients managed without dialysis: recommendations for practice. AB - The numbers of patients dying with end-stage renal disease (ESRD), particularly those managed conservatively (without dialysis) or withdrawing from dialysis is increasing rapidly in developed countries. There is growing awareness of the extensive symptom control needs of these patients. Pain is a common problem, and has been both under-recognized and under-treated. It is challenging to manage, largely because of the constraints very poor renal function places on use of medication. Although pharmacological reviews of opioid use in renal failure have been published, there is a need for clinical recommendations to aid palliative and renal specialists in providing effective pain control. This review describes the pharmacological evidence for and against the use of the different opioid medications, and translates this into clinical recommendations for ESRD patients managed conservatively, not for those on dialysis for whom there are different pharmacological considerations. Acetaminophen (paracetamol) is recommended at Step 1 of the World Health Organization ladder. Of the Step 2 analgesics, tramadol is the least problematic, although dose reduction and increased dosing interval are required, and caution should be exercised. Of the Step 3 analgesics, fentanyl, alfentanil and methadone are recommended. There is limited evidence for buprenorphine, although theoretical reasons why it may be a good choice for these patients. Hydromorphone and oxycodone cannot be recommended because of extremely limited evidence, although each is likely a better choice than morphine or diamorphine. Morphine and diamorphine themselves are not recommended because of known accumulation of potentially toxic metabolites. PMID- 17844724 TI - Evaluating hospice services for improvement: a manageable approach. AB - Over the past thirty years, hospice services across the United States have been established as a viable alternative for terminally ill patients. As expected, during this period of stabilization, hospice service leaders have invested the majority of their energy in securing funding, developing coalitions, and developing/implementing services. All of this work has occurred to support the primary aim of symptom control for patients through use of pharmacotherapy, as well as provision of ancillary services by interdisciplinary teams consisting of nurses, social workers, pastoral care staff, occupational therapists, and others. Little attention has been given to assessing the effectiveness of this range of services in a holistic way. This paper presents a model of evaluation that is both manageable to implement and suitable to the political environments where hospice providers reside. The article demonstrates an approach that is collaborative and directs the evaluative process towards the improvement of services. PMID- 17844725 TI - Novel opioid antagonists for opioid-induced bowel dysfunction and postoperative ileus. AB - Methylnaltrexone and alvimopan are two new and potentially useful agents in the management of opioid-induced bowel dysfunction and prevention of postoperative ileus. Both agents have promising prokinetic properties and appear to be capable of reversing the effects of opioids on delayed gastrointestinal transit. This article reviews currently available published literature to provide an overview of the clinical trials and to provide insight for the potential use of these agents for patients requiring opioid based analgesia. These compounds represent a new class of compounds that may impact the therapeutics for opioid induced bowel dysfunction as well as postoperative ileus. PMID- 17844726 TI - The "general recognition and acceptance" standard of objectivity for good faith in prescribing: legal and medical implications. AB - The United States Court of Appeals for the 4th Circuit has ruled that a jury considering charges of drug trafficking against a pain management physician should be instructed that the defendant's good faith is a defense to the charges. The court rejected a subjective standard of good faith, and instead ruled that the good faith of the defendant must be evaluated from an objective perspective. This objective standard requires that the jury determine whether the defendant was practicing in accordance with the standard generally recognized and accepted in the United States. General recognition and acceptance are determined on a case by-case basis, within the context of a defendant's practice. Simply because a physician's practice is out of the norm for many physicians does not mean it can't be generally recognized and accepted within the standard of medical practice. Expert witness testimony of pain management physicians will assist juries in the application of this standard for good faith in prescribing. PMID- 17844727 TI - Management strategies for neuropathic pain in different European countries. AB - Many healthcare professionals are aware of the management protocols for nociceptive pain. However, the diagnosis and management of neuropathic pain remains, for many. a confusing and uncertain topic. This paper looks at neuropathic pain management in two countries, Poland and the Republic of Ireland, and discusses the analgesic strategies for the management of this common type of pain. PMID- 17844728 TI - Prescribing policies of opioids for chronic pain. AB - The prescription of opioids often poses a difficult problem for the practitioner, particularly when they are confronted with institutionalised fears and restrictive regulations. This article compares prescribing policies for opioids in three European countries, Austria, Israel and Portugal. PMID- 17844729 TI - Carpal tunnel syndrome, diabetic neuropathy, fibromyalgia, glucosamine and chondroitin, hypnosis in pain management, marijuana for pain. AB - This feature presents information for patients in a question and answer format. It is written to simulate actual questions that many pain patients ask and to provide answers in a context and language that most pain patients will comprehend. Issues addressed in this issue are carpel tunnel syndrome, fibromyalgia, glucosamine and chondroitin, hypnosis, marijuana. PMID- 17844730 TI - Death, narcotic overdose, and serious cardiac arrhythmias: information for healthcare professionals on methadone. AB - In November, 2006, the United States Food and Drug Administration issued a Health Alert for health professionals on risks of death, cardiac arrhythmias, and narcotic overdose associated with methadone. That alert is reproduced below. PMID- 17844731 TI - Concomitant use of ibuprofen and aspirin. AB - Last September, the U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) published the following notice for consumers and healthcare professionals cautioning about the interference with the antiplatelet effects of low dose aspirin that can occur when aspirin is taken concomitantly with ibuprofen. PMID- 17844732 TI - Dispensing controlled substances for the treatment of pain issuance of multiple prescriptions for schedule II controlled substances. AB - On January 18, 2005, DEA published in the Federal Register a solicitation of comments on the subject of dispensing controlled substances for the treatment of pain. Many of the comments that DEA received asked the agency to elaborate on the legal requirements and agency policy relating to this subject. This document provides such information. PMID- 17844735 TI - Hydrogen-bonded donor--acceptor compounds for organic ferroelectric materials. AB - Organic ferroelectrics are multifunctional candidates for future organic electronic and optical devices. In spite of their potential, only a few organic compounds are known to exhibit a ferroelectric transition. The conventional approach to ferroelectrics, in general, relies on the use of asymmetric dipolar molecules and/or substituents. Recently, distinct design strategies have been developed using the molecular compounds of binary- or multi-components, combined with "non-covalent" forces: charge-transfer interactions and/or hydrogen bonding. This article focuses on the supramolecular systems of hydrogen-bonded acid and base molecules. Ferroelectricity and a significant dielectric response, as well as an antiferroelectric ordering induced by proton transfer, are demonstrated in the hydrogen-bonded chains composed of 2,5-dihydroxy-p-benzoquinone derivatives and nitrogen-containing aromatic bases. PMID- 17844736 TI - Synthesis and reactivity of [18F]-N-fluorobenzenesulfonimide. AB - A novel [18F]NF reagent and two novel radiochemical transformations have been developed: [18F]NFSi has been prepared from sodium dibenzenesulfonimide and reacted in the presence of silyl enol ethers and allylsilanes to deliver labelled fluorinated ketones and allylic fluorides respectively; the radiosynthesis of the fluorinated A ring of vitamin D3 has also been completed with success. PMID- 17844737 TI - Glycol-modified molybdate catalysts for efficient singlet oxygen generation from hydrogen peroxide. AB - Pretreatment of molybdate-exchanged layered double hydroxides in polyalcohols such as ethylene glycol affords heterogeneous catalysts showing largely improved oxidant efficiency compared to the unmodified materials. PMID- 17844738 TI - Efficient, one-pot syntheses of biologically active alpha-linked glycolipids. AB - Per-O-silylated galactosyl iodides undergo alpha-glycosidation with fully functionalized glycolipids producing biologically relevant conjugates. PMID- 17844739 TI - Mechanism of a self-templating synthesis of monodispersed hollow silica nanospheres with tunable size and shell thickness. AB - This study clarifies the mechanism of the hollow structure formation in the simple self-templating preparation of monodispersed hollow silica structures; the role of the polarity of washing solvent in creating the hollow structure is emphasized. PMID- 17844740 TI - Alkynylation of alpha-halocarbonyl compounds--a stille-type cross-coupling for the formation of C(sp)-C(sp3) bonds under neutral conditions. AB - A direct alkynylation of readily available alpha-halo esters and amides with high yields is described herein; a distinct switch from diyne formation to alkynylation products was attained under neutral conditions. PMID- 17844741 TI - Sensitive dopamine recognition by boronic acid functionalized multi-walled carbon nanotubes. AB - Boronic acid functionalized multi-walled carbon nanotubes (MWNTs) have been synthesized and used for sensitive dopamine (DA) detection using electrochemical methods in the presence of excess L-ascorbic acid (L-AA) via specific, reversible formation of a boronate ester between DA and the functionalized MWNTs. PMID- 17844742 TI - Fine-tuning of a ferrocene[porphyrin]ITO redox cascade for efficient sequential electron transfer commenced by an S2 photoexcited special-pair mimic. AB - A systematic series of ferrocene/porphyrin redox cascade architectures was assembled through a slipped-cofacial porphyrin dimer on ITO electrode in optimizing the anodic photocurrent generation to perform the highest quantum yield compared to reported values on ITO electrodes. PMID- 17844743 TI - Macromolecular helicity inversion of an optically active helical poly(phenylacetylene) by chemical modification of the side groups. AB - An optically active helical poly(phenylacetylene) was synthesized by the copolymerization of phenylacetylenes bearing optically active hydroxy or ester groups obtained by the kinetic resolution of a racemic phenylacetylene with lipase; the helix-sense was inverted from one helix to another by the further chemical modification of the hydroxy groups with achiral bulky isocyanates or an acid chloride. PMID- 17844744 TI - Copper-catalyzed oxidative desulfurization-oxygenation of thiocarbonyl compounds using molecular oxygen: an efficient method for the preparation of oxygen isotopically labeled carbonyl compounds. AB - A novel copper-catalyzed oxidative desulfurization reaction of thiocarbonyl compounds, using molecular oxygen as an oxidant and leading to formation of carbonyl compounds, has been developed, and the utility of the process is demonstrated by its application to the preparation of a carbonyl-18O labeled sialic acid derivative. PMID- 17844745 TI - Transmitting information along oligo-para-phenylenes: 1,12-stereochemical control in a terphenyl tetracarboxamide. AB - Amide-substituted terphenyls adopt a well-defined conformation that allows the transmission of stereochemical information from a controlling centre to a reaction site 11 bond lengths away, providing a model of how extended polymeric systems might be used to communicate binary information. PMID- 17844747 TI - A new zinc-zinc-bonded compound with a dianionic alpha-diimine ligand: synthesis and structure of [Na(THF)2]2 x [LZn-ZnL] (L = [(2,6-(i)Pr2C6H3)N(Me)C]2(2-)). AB - The synthesis and structure of a Zn-Zn-bonded compound supported by a doubly reduced alpha-diimine ligand, [Na(THF)2]2 x [LZn-ZnL] (L = [(2,6 (i)Pr2C6H3)N(Me)C]2(2-)) are reported, with a Zn-Zn bond length of 2.399(1) angstroms. PMID- 17844746 TI - Facile preparation of stabilized polymeric nanotubes using sacrificial yttrium hydroxide nanotubes as template and block copolymer micelles as precursor. AB - We report here facile preparation of stabilized polymeric nanotubes with a hair like shell using yttrium hydroxide nanotubes as the sacrificial template and block copolymer micelles as the precursor, and orientation of the polymeric nanotubes encapsulating magnetic particles under magnetic field. PMID- 17844749 TI - Physicochemical characterization of octakis(alkyloxy)-substituted Zn(II) phthalocyanines non-covalently incorporated into an organogel and their remarkable morphological effect on the nanoscale-fibers. AB - A series of octakis(alkyloxy)-substituted Zn(II)-phthalocyanines were efficiently incorporated into an organogel made of (1R,2R)-trans-1,2 bis(dodecanoylamino)cyclohexane by means of multiple cooperative non-covalent interactions, and SEM revealed the formation of unique brush-like nanostructures. PMID- 17844748 TI - Pattern-based sensing of nucleotides in aqueous solution with a multicomponent indicator displacement assay. AB - A multicomponent indicator displacement assay (MIDA) based on an organometallic receptor and three dyes can be used for the identification and quantification of nucleotides in aqueous solution at neutral pH. PMID- 17844750 TI - Carborane radical anions: spectroscopic and electronic properties of a carborane radical anion with a 2n + 3 skeletal electron count. AB - One-electron reduction of the well-known carborane 1,2-Ph2-1,2-C2B10H10 (1) gives rise to a stable carborane radical anion ([1]-) with a true 2n + 3 cluster electron count; the geometry of ([1]-) features an elongated C...C cage distance but no significant pi-bonding interactions between the cage and the phenyl substituents. PMID- 17844751 TI - Supramolecular synthon polymorphism in 2 : 1 co-crystal of 4-hydroxybenzoic acid and 2,3,5,6-tetramethylpyrazine. AB - Co-crystals of 4-hydroxybenzoic acid and 2,3,5,6-tetramethylpyrazine (2 : 1) exhibit the first supramolecular synthon polymorphism in a co-crystal; metastable anti-hierarchic polymorph I converts to stable hierarchic form II. PMID- 17844752 TI - Evaluation of planarity and aromaticity in sapphyrin and inverted sapphyrin using a bidirectional NICS (Nucleus-Independent Chemical Shift) scan method? AB - Using the bidirectional NICS scan method in conjunction with two-photon absorption (TPA) measurements, it has proved possible to determine the relationship between pi-conjugation and aromaticity in two structurally related expanded porphyrin systems, sapphyrin and inverted sapphyrin, and establish that differences in these defining factors depend on the presence or absence of a key sp3 hybrid molecular orbital within the macrocyclic periphery. PMID- 17844753 TI - New insights into the enantioselectivity in the hydrogenation of prochiral ketones. AB - The high enantioselectivity in the hydrogenation of acetophenone catalysed by trans-Ru(H)2(S,S-dpen)(S-xylbinap) is explained in terms of the existence of a stable intermediate formed when the reactant enters the catalyst pocket fixing the molecular orientation. PMID- 17844755 TI - A cyclodextrin-insulated anthracene rotaxane with enhanced fluorescence and photostability. AB - A beta-cyclodextrin anthracene rotaxane was synthesized and found to be significantly more resistant to fluorescence quenching and photobleaching than the uninsulated anthracene derivative. PMID- 17844754 TI - Self-assembly of amphiphilic imidazolium-based hexa-peri-hexabenzocoronenes into fibreous aggregates. AB - Imidazolium-based amphiphilic hexa-peri-hexabenzocoronenes were synthesized and shown to undergo ordered columnar self-assembly in solid-state as well as in solution to yield defined nanofibers upon solution drop casting onto solid substrate. PMID- 17844756 TI - Selective disaccharide binding by a macrotetracyclic receptor. AB - A new carbohydrate receptor possesses a C3-symmetric polar cavity capable of encapsulating disaccharides; binding to beta-maltosyl is preferred, complementing previous systems which have favoured "all-equatorial" substrates. PMID- 17844757 TI - Icosahedral galloxane clusters. AB - Hydrolysis of 'tris(aryl or alkyl)gallium(III)' species results in the formation of spheroidal dodecameric galloxane mixed oxide-hydroxide clusters, and shows that the gallium centres and associated residual alkyl/aryl groups are arranged at the polyhedral vertices of pseudo-icosahedra. PMID- 17844758 TI - Efficient proton conduction in dry nanofilms of amorphous aluminosilicate. AB - Amorphous aluminosilicate nanofilms as prepared by a sol-gel process and post annealing exhibit proton conduction at a wide temperature range in dry air with a lowest area specific resistance of 0.24 omega cm2 at 400 degrees C. PMID- 17844759 TI - Hydrogen-bond quenching of photodecarbonylation in the solid state and recovery of reactivity by co-crystallization. AB - Intermolecular H-bonding between C=O (ketone) and HO (4'-hydroxyphenyl) quenches photodecarbonylation of 2,2,4,4-tetramethyl-1,3-di(4'-hydroxyphenyl)acetone 1 in the crystalline solid state, its reactivity is recovered by co-crystallization with the small organic molecule 4,4'-bicyclohexanone. PMID- 17844760 TI - Lewis base stabilized lithium TMP-aluminates: an unexpected fragmentation and capture reaction involving cyclic ether 1,4-dioxane. AB - Three Lewis base variations of the synthetically useful aluminate [L x Li(TMP)((i)Bu)Al((i)Bu)2], where L is TMPH, Et3N or PhC(=O)N(i)Pr2, are reported, together with the reaction of the benzamide complex with 1,4-dioxane, which surprisingly leads to fragmentation of the cyclic ether and capture of its alkoxy vinyl ether residue within a novel dilithium dialuminium hexaalkyl aggregate. PMID- 17844761 TI - Insertion of arynes into carbon-halogen sigma-bonds: regioselective acylation of aromatic rings. AB - Arynes were found to insert into carbon-halogen sigma-bonds of various acid halides, enabling acyl and halogen moieties to be introduced simultaneously into adjacent positions of aromatic rings. PMID- 17844762 TI - Asymmetric aldol reactions under normal and inverse addition modes of the reagents. AB - Both syn- and anti-aldol products can be obtained from common reactants by simply changing their addition sequence. PMID- 17844763 TI - Short synthesis of the C16-C28 polyketide fragment of apoptolidin A aglycone. AB - Starting from (E,E)-1-[(1R)-(phenylethyl)oxy]-2-methylpenta-1,3-diene and triethylsilyl enol ether of butanone rapid access to Koert's advanced C10-C28 polyketide fragment of apoptolidin A is now possible. PMID- 17844764 TI - Starch-assisted synthesis of polypyrrole nanowires by a simple electrochemical approach. AB - Starch, one of the most commonly used polysaccharides, has been adopted for the first time as morphology-directing agent to the electrochemical synthesis of polypyrrole (PPy) nanowires on various electrodes. PMID- 17844765 TI - Amine-induced growth of an In2O3 shell on colloidal InP nanocrystals. AB - A simple and rapid method for the growth of an In2O3 shell on colloidal InP nanocrystals is described, increasing their fluorescence efficiency by one order of magnitude. PMID- 17844767 TI - Amido pincer complex of nickel-catalysed Kumada cross-coupling reactions. AB - Novel nickel complexes bearing P,N,P-, P,N,N- and N,N,N-amido pincer ligands exhibited highly catalytic activity in Kumada coupling reactions. PMID- 17844766 TI - A triazole-templated ring-closing metathesis for constructing novel fused and bridged triazoles. AB - The feasibility of trapping the vinyl copper intermediate generated in situ from azide-[3 + 2] cycloadditions and viability of employing these triazoles as unique templates for ring-closing metathesis are described here; this work effectively combines the two powerful reactions for the first time to construct various de novo fused and bridged triazoles that are otherwise not trivial to synthesize. PMID- 17844768 TI - Looming threats to the intimate bond in hospice care? Economic and organizational pressures in the case study of a hospice. AB - Hospice organizations are assailed by stiff competition, ever-rising costs, limited funding, and policy changes. Do such pressures stifle the high quality of care these organizations strive to provide? As a case-in-point, we draw from the mid-1990s accounts of caregivers at a nonprofit hospice in a Midwestern city in the United States. We maintain that economic pressures drive organizational restructuring, which then weakens working conditions and, thereby, weakens the staff-client relationship. We discuss effects upon worker behaviors, the worker client relationship, and client care. This ethnographic case study signals the need to closely examine the threats that current economic and organizational pressures in the United States may pose to the quality of hospice care. PMID- 17844769 TI - The distribution of mortality in the United States: the effects of income (inequality), social capital, and race. AB - This article examines how absolute and relative income levels, social capital, and racial/ethnic composition interact to explain variation in age-adjusted mortality rates across the 48 contiguous U.S. states. Our data showed that social capital had a powerful, negative effect on age-adjusted mortality rates--higher social capital states had lower age-adjusted mortality rates. After controlling for other variables, median income moderately related to mortality, but unexpectedly three measures of inequality did not. Finally, states' percent African American positively related to mortality, though indirectly and mediated entirely by social capital. In contrast, the strong negative effect of percent Hispanic/Latino on mortality was partially suppressed by its negative association with social capital. Our understanding of the substantial impact of social conditions on mortality can help inform public policies and actions that may foster healthier and longer lives. PMID- 17844770 TI - The role of psychotherapy and humor for death anxiety, death wishes, and aging. AB - This article is part of a series of humor on social attitudes (Richmen, 1977), humor by the elderly (Richman, 1989), assessment (Richman, 1996a), and psychotherapy (Richman, 1996b). The present study is based on the topics of humor related to death anxiety and wishes, and aging that emerged during psychotherapy with elderly patients. The healing qualities of laughter and humor have been observed since Biblical times to the present, however the applications of humor to professional psychotherapy is still in its infancy. The examples in this study spell out how humor in therapy can bring people together, and help them affirm life and laugh at anxiety, depression, and their problems in living. PMID- 17844771 TI - Preventing suicide by educating general practitioners. AB - An education program for GPs about treating patients with depressive disorders and panic disorders was implemented in one district in the year 1998. A neighboring district was used as a control. Although the educational program was followed by an increase in referrals for panic disorder in the target district, there was no impact on referrals for depressive disorders, the prescribing of antidepressants by the GPs, or the suicide rate. PMID- 17844772 TI - Heaping in anniversary reaction studies: a cautionary note. AB - Several studies have reported evidence that death is often associated with significant ceremonial events like holidays and birthdays, a phenomenon variously called the "anniversary reaction," "holiday effect," "birthday blues," etc. This article, using data from the social security death index (SSDI), shows how evidence for this phenomenon can arise from an artifact in death records called "death heaping" in which certain dates, usually the 1st or the 15th, are systematically entered for missing data. In this study, each calendar birthday for the year 2003 in the SSDI was paired with either the 14th or 15th calendar day of death. For each pairing, there were more deaths for the 15th than the 14th. A second analysis compared the correspondence between dying on the same day of the month as one's birthday for the first 28 days of the month. A significantly greater number of birth-death combinations occurred for the 1st and 15th day of the month. These results suggest that studies of "anniversary reactions" should conduct preliminary evaluations to consider the possibility that statistically significant relationships do not arise from "death heaping." PMID- 17844774 TI - Are we doing enough for neonatal pain management? PMID- 17844773 TI - Death preparation and anxiety: a survey in Hong Kong. AB - This study reports the results of a survey on death preparation, death-related beliefs, and death anxiety in a Hong Kong sample. Respondents (N = 285) recruited from the community were asked if they have prepared for themselves a life insurance, a will, and a resting place (e.g. burial site, columbarium, etc.). Questions about their death-related cultural beliefs and anxiety were also asked. Results indicated that respondents who have thought of preparing for their own deaths but not yet acted out (contemplators) held stronger traditional cultural beliefs about death than respondents who have either done the preparations (planners) or never thought of the idea (non-contemplators). Contemplators also reported higher death anxiety. Despite limitations of the study's design, the current results suggest the beliefs in cultural taboo may play a role in the preparation for one's death. PMID- 17844775 TI - Successful treatment of atrial flutter with amiodarone in a premature neonate. Case report and literature review. AB - This case report describes a 30-week gestation neonate who presented at birth with hydrops fetalis due to atrial flutter. Digoxin and electric cardioversion were unsuccessful in maintaining a stable sinus rhythm. The infant continued with intractable atrial flutter and severe hemodynamic deterioration until intravenous loading of amiodarone achieved conversion to stable sinus rhythm. Amiodarone was continued for 45 days; there was no recurrence of atrial flutter. Of note, the infant developed severe chronic lung disease after mechanical ventilation for 28 days. A lung biopsy ruled out amiodarone-induced pulmonary toxicity. A table is provided reviewing the different forms of neonatal supraventricular tachycardias. Apart from the successful management of the tachycardia, the role of amiodarone as an effective antiarrhythmic agent and its potential side effects, such as pulmonary toxicity and transient hypothyroidism, are discussed. PMID- 17844776 TI - Technological advances for PICC placement and management. AB - Placement of a peripherally inserted central catheter (PICC) is often complicated by the infant's small size and previous use of the peripheral veins, making the traditional means of insertion inadequate. New techniques and technologies, previously reserved for pediatric and adult patients, are now available for use in neonates and can enhance the practice of neonatal PICC teams. The modified Seldinger technique allows insertion of the PICC via smaller peripheral veins while decreasing venous trauma and enhancing the rate of successful placement. A second useful technique, the catheter exchange procedure, allows insertion of a new catheter within the same vein when complications such as occlusion, breakage, or inappropriate position occur and require removal of the currently dwelling PICC. Clinicians caring for neonates and infants must continually update their knowledge and skill by incorporating new techniques into their practice. PMID- 17844777 TI - Prune belly syndrome. A focused physical assessment. AB - Prune belly syndrome, a rare congenital anomaly, exists almost exclusively in males and consists of genital and urinary abnormalities with partial or complete absence of abdominal wall musculature. The syndrome, caused by urethral obstruction early in development, is the result of massive bladder distention and urinary ascites, leading to degeneration of the abdominal wall musculature and failure of testicular descent. The impaired elimination of urine from the bladder leads to oligohydramnios, pulmonary hypoplasia, and Potter's facies. The syndrome has a broad spectrum of affected anatomy with different levels of severity. The exact etiology of prune belly syndrome is unknown, although several embryologic theories attempt to explain the anomaly. With advances in prenatal screening techniques, the diagnosis and possible treatment of prune belly syndrome can occur before birth, although controversy exists on the proper management of prune belly syndrome. This article explores the theories behind the pathophysiology and embryology of prune belly syndrome and its multisystemic effects on the newborn infant. Specific attention is paid to presentation, clinical features, head-to toe physical assessment, family support, and nursing care of infants with prune belly syndrome. PMID- 17844778 TI - A TIME for nursing portfolios. A tool for career development. AB - Nursing portfolios are purposeful collections of a nurse's tangible and intangible skills, including critical thinking, communication, and clinical abilities. They can be used for any number of creative career and professional development paths. Nurses should select portfolio pieces representative of their personal philosophy of nursing and display the professional image they choose to create. Through self-reflection, neonatal nurses may showcase talents they feel make their practice distinctive. This article describes the purpose, importance, process, and uses of professional nursing portfolio development. Through the process of self-reflective practice and clinical experience, nurses are empowered to continue on the path of career development and professionalism. PMID- 17844779 TI - Prevention and management of pain in the neonate. An update. AB - The prevention of pain in neonates should be the goal of all caregivers, because repeated painful exposures have the potential for deleterious consequences. Neonates at greatest risk of neurodevelopmental impairment as a result of preterm birth (ie, the smallest and sickest) are also those most likely to be exposed to the greatest number of painful stimuli in the NICU. Although there are major gaps in our knowledge regarding the most effective way to prevent and relieve pain in neonates, proven and safe therapies are currently underused for routine minor yet painful procedures. Every health care facility caring for neonates should implement an effective pain-prevention program, which includes strategies for routinely assessing pain, minimizing the number of painful procedures performed, effectively using pharmacologic and nonpharmacologic therapies for the prevention of pain associated with routine minor procedures, and eliminating pain associated with surgery and other major procedures. PMID- 17844780 TI - Vaccine preventable diseases and vaccination coverage in Australia, 2003 to 2005. PMID- 17844781 TI - An analysis of smoking demographics in HMS DRAKE and an update on smoking cessation support. PMID- 17844782 TI - Vertebral wedge fracture after speedboat 'splash down'. AB - A case is presented of a soldier with wedge fracture of T12 sustained after an axial compression (+/- flexion) injury in a Rigid-Hull Inflatable Boat (RIB). Very powerful boats, such as RIBs, are used on a daily basis in the Royal Navy (RN). Despite this, fractures of the spine are unusual (1). This study explores the mechanism of injury and illustrates that a wedge fracture should be considered in anyone presenting with back pain after a 'splash down' injury. PMID- 17844783 TI - Out of Programme Experience Auckland 2005. PMID- 17844784 TI - A right to benefit from international research: a new approach to capacity building in less-developed countries. AB - This article proposes a means by which benefits provided in international research collaborations might be employed to strengthen health care, research, and other capacities in less-developed countries. The Declaration of Helsinki and CIOMS Guidelines define certain expectations of benefits, but these requirements are ambiguous, logistically problematic, and studies suggest they are inconsistently upheld. Drawing on the principle of respect for persons, a right to benefit from hosting externally-sponsored research is proposed. This right guarantees host communities benefits of a certain value, the nature and use of which is controlled by indigenous personnel. Suggestions are made as to how implementation of this right, using structured incentives, may systematically promote capacity building in host communities. PMID- 17844785 TI - The Research Environment Norm Inventory (RENI): a study of integrity in research administrative systems. AB - University research administrators have been generally ignored in basic studies of research integrity. Hensley noted that research administrators are "essential... to the achievement of the specific missions of postsecondary institutions... and to science and the academic infrastructure". The following study sought to extend the scope of research on research integrity to research administrative structures with a new instrument called the Research Environment Norm Inventory or RENI. University research administrators and their professional association were targeted for data collection. Evidence suggested that research administration in the United States supports integrity in the research environment through: (1) respect for community; (2) respect for institutional boundaries; (3) professionalism; (4) respect for authority structures; (5) sensitivity to system conflicts. The study suggested that integrity structures are dictated largely by the institutional settings and environments. PMID- 17844786 TI - The ethical issues in uranium mining research in the Navajo Nation. AB - We explore the experience of Navajo communities living under the shadow of nuclear age fallout who were subjects of five decades of research. In this historical analysis of public health (epidemiological) research conducted in the Navajo lands since the inception of uranium mining from the 1950s untill the end of the 20th century, we analyze the successes and failures in the research initiatives conducted on Navajo lands, the ethical breaches, and the harms and benefits that this research has brought about to the community. We discuss how scientific and moral uncertainty, lack of full stakeholder participation and community wide outreach and education can impact ethical decisions made in research. PMID- 17844787 TI - ASCs: we can't drive 65. Physicians group says CMS' new ASC compensation rate, two-thirds of what hospitals make, would be a 'death blow'. AB - Under the CMS' new payment system, ambulatory surgery centers will be reimbursed at only 65% of what hospitals receive for Medicare patients. While ASCs say this could cause them to turn away Medicare patients, Paul Briggs, left, of not-for profit Presbyterian Healthcare Services, Albuquerque, says the rule will level the playing field between hospitals and ASCs. PMID- 17844788 TI - A fiscal nor'easter? MedPAC index proposal could mean big losses for some hospitals, gains for others. PMID- 17844789 TI - Device deals dominate. DJO, Biomet buyouts gain steam as Abbott's fizzles. PMID- 17844790 TI - Kaiser probed again. More patient dumping alleged in Los Angeles area. PMID- 17844791 TI - Invasion of privacy? Some IT vendors' contracts ignore HIPAA rules: Tang. PMID- 17844792 TI - Carmona! Carmona! Carmona! After four silent years, it's too late for tough talk from the former surgeon general. PMID- 17844793 TI - One for all. My plan is the only true universal coverage initiative in this campaign. PMID- 17844795 TI - The top exchange rate. GHX dominates as multivendor purchasing portal. PMID- 17844794 TI - The patient's perspective. Hospitals must report patient-satisfaction data or face a financial hit; for many it's just business as usual, for others it poses some challenges. PMID- 17844797 TI - [Pancoast-Tobias syndrome]. PMID- 17844796 TI - [Parvovirus B19: importance of diathesis in the clinical expression of a common infection]. AB - Symptomatic manifestations of parvovirus B19 infection range from harmless conditions such as 5th disease of the child or arthropathy of the middle-aged woman to life threatening disease such as transient aplastic crisis during sickle cell disease, chronic anaemia in immunodeficiency states or hydrops foetalis during pregnancy. Increasing knowledge of parvovirus B19 has led to a better understanding about how a single and unvariant erythrovirus causes such a variety of diseases. The importance of age, hematopoietic and immune status has been raised and besides, effective diagnostic assays, treatments and possibly vaccine have been developed that can be rationally used at the light of this knowledge. PMID- 17844798 TI - [Childhood cancers]. PMID- 17844799 TI - [Epidemiology of childhood cancers]. AB - In industrial countries, 1 child out of 500 develops a cancer before the age of 15 years, and before the age of 6 years for almost half of them. In France, incidence rates were stable over the 15 last years with around 1500 cases each year. A very small fraction of cases is attributable to known risk factors, including heritable cancers or cancers in children with heritable predisposing diseases, cancers induced by high doses of ionizing radiation of medical or accidental origin, by chemotherapeutic or immunosuppressive drugs. Responsibility of Epstein Barr virus in a fraction of Hodgkin's and Burkitt's lymphomas is also established, even though little is still known on the cofactors involved in industrial countries. Other virus could cause leukaemia, as suggested by localized increases in incidence in various conditions of population mixing. Conversely, there is some evidence that early common infections could be protective toward leukaemia risk, probably through their contribution to the maturation of the immune system. Several agents are suspected to induce chemical cancers, particularly pesticides, which are consistently reported in childhood leukaemia and brain tumours. It is more and more likely that genetic factors may modulate risk induced of environmental factors. PMID- 17844800 TI - [Good prognosis childhood cancers]. AB - Wilms' tumours, neuroblastomas occurring in patients aged less than 1 year or localized neuroblastomas in older patients, malignant germ cells tumours, Hodgkin's disease, and malignant non Hodgkin lymphomas can be cured in more than 80% of the cases with treatment strategies adapted to risks factors in each tumour. The knowledge of low risk groups of patients allows the decrease of cumulative doses of alkylating agents and anthracyclines and limits the use of irradiation in order to reduce long term sequelae. PMID- 17844801 TI - [Malignant tumours of the locomotor apparatus in children: an "intermediate" prognosis]. AB - Malignant tumours of the locomotor apparatus in children mainly comprise bone tumours such as osteosarcoma or Ewing's sarcoma and soft tissue sarcomas such as rhabdomyosarcoma. The diagnosis must be considered in any case of progressively worsening limb pain at a fixed site, possibly associated with a soft tissue mass. Standard radiological examinations, Doppler ultrasound, then MRI confirm the diagnosis of a solid tumour, allow staging and may sometimes suggest the invasive nature of the tumour. The biopsy provides a precise histological diagnosis. A frozen section is usually necessary to confirm this diagnosis using the currently available genetic biology tools. Treatment must be adapted to the known prognostic factors, mainly tumour operability, initial size, histological type, response to neoadjuvant chemotherapy and initial staging. Treatment must comprise neoadjuvant chemotherapy followed by local treatment combining radical surgery with reconstruction if necessary and sometimes external beam radiotherapy. This treatment must be completed by postoperative adjuvant chemotherapy resulting in an average total duration of treatment between 6 and 12 months. Long-term follow up is designed to ensure absence of disease recurrence, attentive orthopaedic follow-up and absence of late sequelae related to anticancer therapy. PMID- 17844802 TI - [Poor prognosis childhood cancers]. AB - Poor prognosis childhood cancers are mainly metastatic diseases represented by stage IV neuroblastomas developed in children more than one year and metastatic Ewing tumours. These both diseases are chemosensitive but not curable with conventional chemotherapy. In these indications, high-dose chemotherapy with autologous peripheral blood stem cells transplantation is delivered in patients achieving a good partial remission with conventional treatment. The toxicity of these procedures is high but manageable; these approaches have improved the prognosis of these patients. PMID- 17844803 TI - [Specificities in the therapeutic management of children with cancer]. AB - Treatment and supportive care of children with cancer differ significantly from that of adult oncology with specificities of the initial diagnostic talk, of the therapeutic strategies at diagnosis, relapse or during palliative care, as well as the particularities of chemotherapy administration, surgical procedures and radiation therapy in paediatric oncology. PMID- 17844804 TI - [How to help the child and his/her family to go through the ordeal of cancer]. AB - Experiencing cancer is an ordeal for a child and his/her family, even if the majority of these children are cured. In order to alleviate destabilization or possible psychological sequels, the medical staff must be competent and also provide supportive care and information, so that mutual knowledge and confidence can be established. The child's and adolescent's specific landmarks must be protected (school, friends, play, fantasy, creativity, body image, sense of beauty and of identity, self confidence and trust in their parents, relation with their siblings, plans...). Parents also need assistance for possible practical, social, financial difficulties and, most of all, to maintain confidence in their parental competence. Siblings need help to understand the situation and to cope with it. Accompanying the child when the treatment is over will allow him/her to resume a normal life or to cope with possible sequels. If the child dies, accompanying the parents and the siblings through the grieving process is helpful. The psycholo-oncologist helps the child and his/her family to understand their emotions and their conscious and unconscious thoughts, and to live through this ordeal. PMID- 17844805 TI - [Impact of parent organisations in social aspects of cancer childhood care]. AB - Since 1980, childhood cancer parent organisations study children and familial needs in the cancer of children context and give responses for all members of these families. Today, implications of parent organisations are done professionally and are varied. In regards with two examples, one in French social domain nd another in European therapeutic field, European regulation on medicinal products for paediatric use, we want to demonstrate how high quality partnerships build good developments and take part in "the best cure" for these children. The parents and medical staff are thus relieved of stress and daily preoccupations. PMID- 17844806 TI - [Daily allocation of parental presence]. PMID- 17844807 TI - [From internet to national ranking exam]. PMID- 17844808 TI - [National ranking exam. N43. What could fall at the exam?]. PMID- 17844809 TI - [Cough in the child and the adult (with treatment)]. PMID- 17844810 TI - [Chronic diarrhoea]. PMID- 17844811 TI - [Allergies and hypersensibility in childhood and adult]. PMID- 17844812 TI - [Angina pectoris and myocardial infarction]. PMID- 17844813 TI - [Jean Bergonie, journalist]. PMID- 17844814 TI - Basic ultrasound beam formation and instrumentation. AB - This article is a brief review of ultrasound beam formation. Some detailed components of the ultrasound machine are discussed as a primer for the subsequent article on recent technological advances. The components of the ultrasound transducer responsible for broad bandwidth technology and electronic focusing are discussed in the context of optimizing resolution. Other aspects of ultrasound physics, including artifacts and interactions with matter, are not discussed. PMID- 17844815 TI - Recent advances in ultrasound technology. AB - Technical improvements have made profound changes in diagnostic ultrasound imaging. Some of these changes, such as encoded pulses and receive focusing, occur in the background and are essentially nonadjustable. Others, including harmonics and compounding, are real-time options and are adjustable by the imager. New technologies that offer great promise for improved characterization of lesions include contrast ultrasound and elastography. This article will attempt to update the small animal imager on the clinical applications of these newer technologies. PMID- 17844816 TI - The sonographic search for portosystemic shunts. AB - The diagnostic investigation of portosystemic shunts (PSS) has evolved over the last few decades, helping to understand and identify these vascular anomalies that affect many dogs and cats. Ultrasonography has become an important tool in small animals and high-resolution systems are now widely available. Several sonographic features are observed with the different types of congenital and acquired PSS. A systematic, stepwise approach is described to facilitate ultrasound diagnosis of PSS in small animals. PMID- 17844817 TI - Sonographic evaluation of the normal and abnormal pancreas. AB - Pancreatic disorders in dogs and cats are recognized with increasing frequency, and abdominal ultrasonography has assumed an important role in their diagnosis. The normal pancreas is a small, inconspicuous organ of comparable echogenicity to surrounding mesentery and may be difficult to identify. Therefore, knowledge of anatomic landmarks such as portal vein and contributing vessels, duodenum, and stomach is necessary to facilitate identification and examination. Pancreatic diseases and abnormalities frequently investigated by means of ultrasonography include pancreatitis, pseudocysts, abscesses, neoplastic lesions, and nodular hyperplasia. Disorders less commonly seen include exocrine pancreatic insufficiency, pancreatolithiasis, congenital anomalies, and pancreatic edema. Unfortunately, ultrasonographic findings in various pancreatic disorders overlap, and incidental findings or age-related changes may mimic pancreatic disease. On the other hand, pancreatic disorders may not cause changes in ultrasonographic appearance. Ultrasonographic findings, therefore, have to be judged in light of signalment, history, and laboratory data. Cytology or histopathology may be needed to establish a definite diagnosis. Despite these limitations, ultrasonography is useful in diagnosing pancreatic disease, guiding aspirates and biopsies, and monitoring response to treatment. PMID- 17844818 TI - Two-dimensional grayscale ultrasound and spectral Doppler waveform evaluation of dogs with chronic enteropathies. AB - Sonography is an important diagnostic tool to examine the gastrointestinal tract of dogs with chronic diarrhea. Two-dimensional grayscale ultrasound parameters to assess for various enteropathies primarily focus on wall thickness and layering. Mild, generalized thickening of the intestinal wall with maintenance of the wall layering is common in inflammatory bowel disease. Quantitative and semi quantitative spectral Doppler arterial waveform analysis can be utilized for various enteropathies, including inflammatory bowel disease and food allergies. Dogs with inflammatory bowel disease have inadequate hemodynamic responses during digestion of food. Dogs with food allergies have prolonged vasodilation and lower resistive and pulsatility indices after eating allergen-inducing foods. PMID- 17844819 TI - The sonographic evaluation of lymph nodes. AB - Ultrasound can be used to detect and evaluate both normal and abnormal lymph nodes, as well as aid in biopsy sampling procedures, an important part of staging procedures in cancer patients. Several parameters can be evaluated using ultrasound; lymph node size, margins, echogenicity, echopattern (echotexture), acoustic transmission, presence and distribution of vascular flow, and vascular flow indices. The most diagnostically helpful include the short/long axis ratio of the lymph node, the pattern of distribution of the blood vessels within the lymph node, and to some extent the resistive and pulsatility indices. This review discusses the use of ultrasound for detecting, evaluating, and sampling peripheral, abdominal and thoracic lymph nodes in small animals. PMID- 17844820 TI - Image dissemination and archiving. AB - Images generated as part of the sonographic examination are an integral part of the medical record and must be retained according to local regulations. The standard medical image format, known as DICOM (Digital Imaging and COmmunications in Medicine) makes it possible for images from many different imaging modalities, including ultrasound, to be distributed via a standard internet network to distant viewing workstations and a central archive in an almost seamless fashion. The DICOM standard is a truly universal standard for the dissemination of medical images. When purchasing an ultrasound unit, the consumer should research the unit's capacity to generate images in a DICOM format, especially if one wishes interconnectivity with viewing workstations and an image archive that stores other medical images. PACS, an acronym for Picture Archive and Communication System refers to the infrastructure that links modalities, workstations, the image archive, and the medical record information system into an integrated system, allowing for efficient electronic distribution and storage of medical images and access to medical record data. PMID- 17844821 TI - Pay review body's remit extended to cover plumbers and bricklayers. PMID- 17844822 TI - Spearheading improvement. AB - Service transformation is one of the aims of the NHS Institute. Innovation and knowledge development are firmly rooted in practice. PMID- 17844823 TI - Lifting the spirit. AB - As a nurse, Maitreyabandhu burned the candle at both ends, but was introduced to meditation through the London Buddhist Centre. Now he helps others to prevent relapse of depression. PMID- 17844824 TI - 'Welcome stranger'. PMID- 17844825 TI - Implementing a systematic response to medication errors. AB - Healthcare delivery is associated with various risks and it is unlikely that these can ever be completely eliminated. Medicine management is an area known to involve errors. This article describes how implementing a systematic response to medication errors enables health professionals to identify individual and organisational failures and reduce adverse patient outcomes. PMID- 17844826 TI - Fitting a contraceptive intrauterine device or system. AB - The intrauterine device or system is a safe and effective method of contraception. This article provides a practical, step-by-step guide on how to fit these devices and the advice that needs to be offered to women choosing this method. The information contained within the article should be used alongside formal training and supervision. PMID- 17844827 TI - Obstructive sleep apnoea syndrome: diagnosis and management. AB - Obstructive sleep apnoea syndrome (OSAS) is a common disorder that can negatively affect a person's health and quality of life. Once diagnosed, however, it can be treated successfully. This article provides an overview of the condition, focusing on the signs and symptoms, diagnosis and treatment options. PMID- 17844829 TI - Blowing the whistle. PMID- 17844828 TI - Insulin therapy. PMID- 17844830 TI - Battle stations. PMID- 17844831 TI - Learning to say no. PMID- 17844832 TI - Infections in hospitalized patients: what is happening and who can help? AB - The continuing emergence of multidrug-resistant bacteria calls for new approaches to the management and treatment of infections in hospitalized patients. Health care-associated infections cause substantial morbidity and mortality while driving up health care resource use and costs worldwide. The continued spread of antimicrobial resistance requires a multidisciplinary approach and closer collaboration among health care providers, especially hospitalists, pharmacists, infection control practitioners, and infectious disease specialists. Such collaboration can potentially reduce treatment failures and minimize the spread of multidrug-resistant organisms between health care settings and the community. PMID- 17844833 TI - Johnson and Darzi lead Brown's campaign to woo back voters. PMID- 17844834 TI - Cabinet reshuffle. Communication skills are key as Johnson takes over health. PMID- 17844835 TI - On lessons from Australia. PMID- 17844836 TI - Reform. Forging ahead with lessons from the future. PMID- 17844837 TI - Barometer. Acute trusts June 2007. PMID- 17844838 TI - Maternity care. Eyes on storks. AB - Critics of the DoH's new maternity policy document fear it will be as'pie in the sky' as its predecessor. Midwifery leaders say pay, frozen budgets and frozen posts have led to mass disillusion. One proposed solution for easing the pressure -maternity support workers--has raised safety fears. PMID- 17844839 TI - Social enterprise. Rich seam of ideas. PMID- 17844840 TI - Primary care. Taking care of number one. PMID- 17844841 TI - [Collaboration between the Regional Health and the Agenzia Regionale Prevenzione e Ambiente Lombardia]. PMID- 17844842 TI - [Case-control study on the long-term effects of urban-industrial pollution: the Ravenna experience]. PMID- 17844843 TI - [Evaluation of the health impact of a waste-to-energy incinerator]. PMID- 17844844 TI - [The Laboratorio di Educazione Ambientale and environmental prevention: an integrated management model. ARPA-Departments of Public Health in the Area Vasta Romagna, Emilia-Romagna region]. PMID- 17844845 TI - [Feasibility study of launching an epidemiologic survey of the resident population near the API refinery in Falconara Marittima]. PMID- 17844846 TI - [The asbestos crisis in an urban area: the Bari experience]. PMID- 17844847 TI - [From integration to communication: estimation of potential health benefits of atmospheric pollution reduction in the city of Trieste]. PMID- 17844848 TI - [Risk analysis]. PMID- 17844849 TI - [From risk communication to participant decisions]. PMID- 17844850 TI - [Environmental risk communication and civil rights]. PMID- 17844851 TI - Monitor to government: do not let foundation trusts slip. PMID- 17844852 TI - Reform strategy. Surgeon puts capital at cutting edge of policy. PMID- 17844853 TI - On engagement and alienation. PMID- 17844854 TI - Financial recovery. Moving down the line to financial stability. PMID- 17844855 TI - Data briefing. The new measure for productivity. PMID- 17844856 TI - Mental health. Sounding off. AB - The incidence of mental illness among deaf people is around 40 per cent. Only three NHS services currently provide inpatient and day hospital care for the deaf. Deaf service users are often prepared to travel for specialst care, and some even relocate. PMID- 17844857 TI - Primary care. Continuity drive. AB - Speed of access to primary care is important to patients with straightforward needs but for more serious problems trusted, relational continuity of care is more valued. GP practices need to prioritise relational continuity in providing care for patients, improving their teamwork and taking account of patient preferences. Managers must balance access targets with continuity. PMID- 17844858 TI - Continuity of care. Life support. AB - The advent of patient choice will provide a challenge to continutiy of care for patients. The impact on long-term conditions, where regular patient monitoring is essential, is particularly important. Better use of technology is part of the solution. PMID- 17844859 TI - Care closer to home. Moving care. AB - Shifting services from secondary to primary care and tackling referrals may increase the efficiency and effectiveness of outpatient services. Relocating specialists in primary care or developing joint working between primary and secondary clinicians is of more doubtful value. Investigation facilities should be community based. PMID- 17844860 TI - Care closer to home. Keeping it real. AB - Care closer to home is a core part of service reforms built around patient choice. More choice raises tough questions around sustainability of mass services. To make choices patients will need more access to data. PMID- 17844862 TI - Children's services. Child guidance. AB - Professionals working ith children are at a crossroads between home, school and health services. There is an emphasis on more preventative work. Silo working remains a significant problem in childrn's serivces. PMID- 17844861 TI - Children's services. Early learning. AB - Nurses, midwives and health visitors have a key role to play in the development and delivery of child services. The research project explored the actual and potential contribution of these professionals to child services. To deliver health gains, child services need to worrk within a social model of health sensitive to the context of children's and young people's lives. PMID- 17844863 TI - Private sector. Good neighbours. PMID- 17844864 TI - Mergers. Executive expectations. PMID- 17844865 TI - Contract dispute could drive wedg between GPs and PCTs. PMID- 17844866 TI - Dementia services begin long journey out of dark ages. PMID- 17844867 TI - On PFI passions running high. PMID- 17844868 TI - Money no excuse for hampering progress. Interview by Rebecca Allmark. PMID- 17844869 TI - Data briefing. Cash incentives improve coding. PMID- 17844870 TI - Patient safety. Safe crackers. Panel discussion. PMID- 17844872 TI - Protecting staff. Take action on stalking. PMID- 17844871 TI - Children. Activity project leaps obstacles. PMID- 17844873 TI - European position paper on rhinosinusitis and nasal polyps 2007. AB - Rhinosinusitis is a significant and increasing health problem which results in a large financial burden on society. This evidence based position paper describes what is known about rhinosinusitis and nasal polyps, offers evidence based recommendations on diagnosis and treatment, and considers how we can make progress with research in this area. Rhinitis and sinusitis usually coexist and are concurrent in most individuals; thus, the correct terminology is now rhinosinusitis. Rhinosinusitis (including nasal polyps) is defined as inflammation of the nose and the paranasal sinuses characterised by two or more symptoms, one of which should be either nasal blockage/obstruction/congestion or nasal discharge (anterior/posterior nasal drip), +/- facial pain/pressure, +/- reduction or loss of smell; and either endoscopic signs of polyps and/or mucopurulent discharge primarily from middle meatus and/or; oedema/mucosal obstruction primarily in middle meatus, and/or CT changes showing mucosal changes within the ostiomeatal complex and/or sinuses. The paper gives different definitions for epidemiology, first line and second line treatment and for research. Furthermore the paper describes the anatomy and (patho)physiology, epidemiology and predisposing factors, inflammatory mechanisms, evidence based diagnosis, medical and surgical treatment in acute and chronic rhinosinusitis and nasal polyposis in adults and children. Evidence based schemes for diagnosis and treatment are given for the first and second line clinicians. Moreover attention is given to complications and socio-economic cost of chronic rhinosinusitis and nasal polyps. Last but not least the relation to the lower airways is discussed. PMID- 17844875 TI - Euro35m ISTC deal scrapped. PMID- 17844874 TI - Nicholson: let local managers drive health service reforms. PMID- 17844876 TI - Shelved report exposes PFI management problems. PMID- 17844877 TI - Controversial and divisive: Whitehall's own Big Brother. PMID- 17844878 TI - On teaching hospitals. PMID- 17844879 TI - David vs the Goliaths of bossy government. Interview by Victoria Vaughan. PMID- 17844880 TI - Data briefing. A chorus of approvals. PMID- 17844881 TI - Turning curves. PMID- 17844882 TI - Health for all. What is Healthy Communities programme? PMID- 17844883 TI - Hughes for Utopia. Interview by Saba Salman. PMID- 17844884 TI - Born lucky? To improve public health, first you know your local priorities. PMID- 17844885 TI - Health promotion. Reflections on being well. PMID- 17844886 TI - Funding. Share & share alike. PMID- 17844887 TI - Climate change. NHS heeds the global warning. PMID- 17844888 TI - International development. Have skills, will travel. PMID- 17844889 TI - The myriad challenges of Informed consent. PMID- 17844890 TI - The oncology nurse's role in the informed consent process. AB - Cancer clinical trials are a necessary component of the effort to improve cancer prevention, diagnosis, and treatment. Essential to this process is the informed consent of the individuals who participate in these research studies. The purpose of this article is to describe patient, provider, and informed consent process issues with presentations of data reported in the current literature. The role of nursing in the facilitation of informed consent is discussed. PMID- 17844891 TI - Managing painful surface wounds. PMID- 17844892 TI - Ovarian cancer and lower limb lymphedema. PMID- 17844893 TI - Management of comorbid diabetes and cancer. AB - Diabetes mellitus is a frequent comorbidity of cancer patients. The growing epidemic of diabetes is anticipated to have tremendous impact on health care. Diabetes may negatively impact both cancer risk and outcomes of treatment. Oncology nurses are ideally positioned to identify patients at risk for complications that arise from cancer treatment in the setting of pre-existing diabetes. Additionally, oncology nurses may be the first to identify underlying hyperglycemia/hidden diabetes in a patient undergoing cancer treatment. Strategies for assessment and treatment will be discussed, along with specific strategies for managing hyperglycemia, potential renal toxicity, and peripheral neuropathy. Guidelines for aggressive treatment of hyperglycemia to minimize risks of complications will be reviewed. The role of interdisciplinary care, utilizing current evidence, is crucial to supporting patients and their families as they manage the challenges of facing two life-limiting diseases. Whole-person assessment and individualized treatment plans are key to maximizing quality of life for patients with cancer and diabetes. PMID- 17844894 TI - Nausea and vomiting. PMID- 17844896 TI - Implementing change: a view from the trenches. PMID- 17844895 TI - Radiation dermatitis. PMID- 17844897 TI - Antiemetic agents. PMID- 17844899 TI - What will nutrition summits serve up? PMID- 17844900 TI - Switching off the cult. AB - There are more than 500 cults in Britain but where are the services to support those who leave and go on to develop mental health problems? PMID- 17844901 TI - All day long. Interview by Carol Davis. AB - Hyperemess, severe and excessive vomiting during pregnancy, is a distressing condition that can require hospital treatment. One hospital has set up a dedicated, midwife-led day unit for these women. PMID- 17844902 TI - Strike a balance. PMID- 17844903 TI - Challenges of setting up a multi-centred research study. AB - Multi-centred research studies provide an evidence base to guide nursing practice. However, little has been written about the processes involved in setting up such projects. This article draws on literature to highlight the advantages and disadvantages of multi-centred research studies as well as identifying areas that require particular consideration during the planning stages. The authors reflect on their own experience of submitting a multi-centred research study for funding, outlining the problems encountered and key elements of successful collaboration. PMID- 17844904 TI - Patient preparation for safe removal of surgical drains. AB - Drains are a common feature of the post-operative management of surgical patients. While drains serve an important function they are also associated with complications such as haemorrhage, tissue inflammation, retrograde bacterial migration and drain entrapment. It is therefore essential that nurses are familiar with the monitoring and management of surgical drains, but also the process involved in their removal. PMID- 17844905 TI - Detecting changes in the respiratory status of ward patients. AB - This article outlines the principles of respiratory assessment. It is intended to be a learning tool for all nurses, however, it may have more relevance for nurses on general wards. Such nurses, unlike those who work in intensive care units and accident and emergency (A&E) departments, do not have the advantage of frequent presence of medical staff and may have to intervene promptly and autonomously in response to detected changes. PMID- 17844906 TI - Respiratory assessment in adults. AB - Respiratory disorders are among the most common reasons for admission to critical care units in the U.K. However, anecdotal evidence suggests that nursing assessment of patients' respiratory function is not performed well because it is not considered a priority and the implications of respiratory dysfunction are underestimated. It is essential that nurses are able to recognise and assess symptoms. of respiratory dysfunction to provide early, effective and appropriate interventions, thus improving patient outcomes. This article highlights the role of the nurse in respiratory assessment and discusses the implications of clinical findings. PMID- 17844907 TI - Person-centred care. PMID- 17844908 TI - Liberty and solidarity. PMID- 17844909 TI - Why should we care about social justice? PMID- 17844910 TI - Taking religion seriously. PMID- 17844911 TI - Overseeing quality improvement. PMID- 17844912 TI - Futility, in short. PMID- 17844913 TI - Saving Sylvia Cleary. PMID- 17844914 TI - The cash nexus. PMID- 17844915 TI - Case study. All for one, or one for all? PMID- 17844916 TI - A proposal for modernizing the regulation of human biotechnologies. PMID- 17844917 TI - Managing reproductive pluralism: the case for decentralized governance. PMID- 17844918 TI - Can we trust "democratic deliberation"? PMID- 17844919 TI - The virtues of muddling through. PMID- 17844920 TI - Tied up in nots over genetic parentage. PMID- 17844921 TI - The Hastings Center. Ethics and policy in medicine, medical science, and health care. PMID- 17844922 TI - Social justice and disadvantaged groups. AB - Because an influenza pandemic would create the most serious hardships for those who already face most serious hardships, countries should take special measures to mitigate the effect of a pandemic on existing social inequalities. Unfortunately, there is little evidence that anybody is thinking about that. PMID- 17844923 TI - The privacy rule that's not. AB - HIPAA is often described as a privacy rule. It is not. In fact, HIPAA is a disclosure regulation, and it has effectively dismantled the longstanding moral and legal tradition of patient confidentiality. By permitting broad and easy dissemination of patients' medical information, with no audit trails for most disclosures, it has undermined both medical ethics and the effectiveness of medical care. PMID- 17844924 TI - The ethics of swimming pools. PMID- 17844925 TI - Ten days in Texas. PMID- 17844926 TI - Are shorter work hours good for the environment? A comparison of U.S. and European energy consumption. AB - European employees work fewer hours per year, and use less energy per person, than their American counterparts. This article compares the European and U.S. models of labor productivity, supply, and energy consumption. It finds that if employees in the EU-15 worked as many hours as those in the United States, they would consume at least 15 percent more energy. This aspect of the debate over Europe's economic model reaches globally. Over the coming decades, developing countries will decide how to make use of their increasing productivity. If, by 2050, the world works as do Americans, total energy consumption could be 15 to 30 percent higher than it would be if following a more European model. Translated directly into higher carbon emissions, this could mean an additional 1 to 2 degrees Celsius in global warming. PMID- 17844927 TI - Pediatric CT research elevates public health concerns: low-dose radiation issues are highly politicized. AB - This article presents an analysis of issues related to low-dose radiation, with a focus on pediatric computed tomography (CT). It references several early studies that are seldom quoted in radiation research papers, then quantifies the excess lifetime fatal cancer yield attributable to an estimated 6.5 million pediatric abdominal CT scans. The authors highlight an important policy document issued jointly by the National Cancer Institute and the Society for Pediatric Radiology- specifically, its conclusion that a small dose from CT represents "a public health concern." Finally, the article identifies several contentious issues and proposes policy initiatives that, if implemented, could result in significant reductions of future radiogenic cancers and chronic injuries. The authors call for discussions between professional radiology societies and public interest health organizations, thereby involving all stakeholders. PMID- 17844928 TI - Health insurance eroding for working families: employer-provided coverage declines for fifth consecutive year. AB - In 2005, the percentage of Americans with employer-provided health insurance fell for the fifth year in a row. Workers and their families have been falling into the ranks of the uninsured at alarming rates. The downward trend in employer provided coverage for children also continued into 2005. In the previous four years, children were less likely to become uninsured as public sector health coverage expanded, but in 2005 the rate of uninsured children increased. While Medicaid and SCHIP still work for many, the government has not picked up coverage for everybody who lost insurance. The weakening of this system-notably for children-is particularly difficult for workers and their families in a time of stagnating incomes. Furthermore, these programs are not designed to prevent low income adults or middle- or high-income families from becoming uninsured. Government at the federal and state levels has responded to medical inflation with policy changes that reduce public insurance eligibility or with proposals to reduce government costs. Federal policy proposals to lessen the tax advantage of workplace insurance or to encourage a private purchase system could further destabilize the employer-provided system. Now is a critical time to consider health insurance reform. Several promising solutions could increase access to affordable health care. The key is to create large, varied, and stable risk pools. PMID- 17844929 TI - Limited state progress in regulating secondhand tobacco smoke. AB - From 1990 to 2005, U.S. state legislation on secondhand tobacco smoke significantly increased in eight put c areas: general public areas, government buildings, private workplaces, schools, child care facilities, health care facilities, restaurants, and bars. Despite the U.S. Surgeon General's proclaiming in 2006 that "rapid progress" is being made in state legislation on clean indoor air, vigorous state smoke-free secondhand tobacco smoke legislation in six public area categories was minimal, which has favored the policy agenda of the corporate tobacco lobby. Two exceptions include smoke-free legislation for child care facilities and schools. While public interest group health advocates have traditionally used insider lobbying of public officials in the "halls of power" to pass smoke-free legislation, this should be supplemented with astute outsider advocacy tactics such as public demonstrations or issue advertisements to increase the likelihood of passage of more state-level smoke-free legislation. PMID- 17844930 TI - Changes in Latin America: consequences for human development. AB - This article looks at Latin America's political shift over the last several years. The author argues that these changes have largely been misunderstood and underestimated in the United States for a number of reasons. First, Latin America's unprecedented growth failure over the past 25 years is a major cause of these political changes and has not been well-understood. Second, the collapse of the International Monetary Fund's influence in Latin America, and in middle income countries, is an epoch-making change. Third, the availability of alternative sources of finance, especially from the reserves of the Venezuelan government, has become very important. Finally, the increasing assertion of national control over natural resources is an important part of the new relationship between Latin America and the United States. For these and other reasons, the relationship between Latin America and the United States has undergone a fundamental and possibly irreversible change, and one that opens the way to new and mostly more successful economic policies. PMID- 17844931 TI - The effect of an international embargo on malnutrition and childhood mortality in rural Haiti. AB - The study objective was to determine the effect of an international embargo against Haiti, from October 1991 through October 1994, on early childhood protein energy malnutrition and all-cause mortality in a geographic area where humanitarian aid was continuously available to the children in the study. The authors used longitudinal anthropometric records on 1593 children, 24 months old or younger, living in the rural Grand Anse Department of Haiti from 1989 through 1996. Kaplan-Meier graphs for all-cause mortality accounting for malnutrition status and stratified by calendar period were applied to the database and assessed using logrank tests. Adjusted relative risks were assessed by Cox regression. The results show that despite the continuous availability of preventive services (1989-1996), higher all-cause mortality was more strongly associated with a calendar period coinciding with the international embargo than with periods before and after the embargo. The incidence of childhood mortality and of severe malnutrition were also higher during the period of the embargo than in the periods before and after the embargo. The findings suggest that future international sanctions, even those with humanitarian/medical exceptions, could result in substantial infant death. PMID- 17844932 TI - Health system reform in Mexico: a critical review. AB - Last year Lancet published a series of articles on Mexico's 2004 health system reform. This article reviews the reform and its presentation in the Lancet series. The author sees the 2004 reform as a continuation of those initiated in 1995 at the largest public social security institute and in 1996 at the Ministry of Health, following the same conceptual design: "managed competition". The cornerstone of the 2004 reform-the voluntary Popular Health Insurance (PHI)--will not resolve the problems of the public health care system. The author assesses the robustness and validity of the evidence on which the 2004 reform is based, noting some inconsistencies and methodological errors in the data analysis and in the construction of the "effective coverage" index. Finally, some predictions about the future of PHI are outlined, given its intrinsic weaknesses. The next two or three years are critical for the viability of PHI: both families and states will face increasing difficulties in paying the insurance premium; health infrastructure and staff are insufficient to guarantee the health package services; and the private service contracting will further strain state health ministries' ability to strengthen service supply. Moreover, redistribution of federal health expenditure favoring PHI at the cost of the Social Security Institute will further endanger public health care delivery. PMID- 17844933 TI - The dynamics of gender and class in access to health care: evidence from rural Karnataka, India. AB - In the early 1990s, India embarked upon a course of health sector reform, the impact of which on an already unequal society is now becoming more apparent. This study sought to deepen understanding of equity effects by exploring gender and class dynamics vis-a-vis basic access to health care for self-reported long-term ailments. The authors drew on the results of a cross-sectional household survey in a poor agrarian region of south India to test whether gender bias in treatment seeking is class-neutral and whether class bias is gender-neutral. They found evidence of "pure gender bias" in non-treatment operating against both non-poor and poor women, and evidence of "rationing bias" in discontinued treatment operating against poor women overall, but with some differences between the poor and poorest households. In poor households, men insulated themselves and passed the entire burden of rationing onto women; but among the poorest, men, like women, were forced to curtail treatment. There were economic class differences in continued, discontinued, and no treatment, but class was a gendered phenomenon operating through women, not men. PMID- 17844934 TI - Rural health care in Vietnam and China: conflict between market reforms and social need. AB - China and Vietnam have adopted market reforms in the health sector in the context of market economic reforms. Vietnam has developed a large private health sector, while in China commercialization has occurred mainly in the formal public sector, where user fees are now the main source of facility finance. As a result, the integrity of China's planned health service has been disrupted, especially in poor rural areas. In Vietnam the government has been an important financer of public health facilities and the pre-reform health service is largely intact, although user fees finance an increasing share of facility expenditure. Over servicing of patients to generate revenue occurs in both countries, but more seriously in China. In both countries government health expenditure has declined as a share of total health expenditure and total government expenditure, while out-of-pocket health spending has become the main form of health finance. This has particularly affected the rural poor, deterring them from accessing health care. Assistance for the poor to meet public-sector user fees is more beneficial and widespread in Vietnam than China. China is now criticizing the degree of commercialization of its health system and considers its health reforms "basically unsuccessful." Market reforms that stimulate growth in the economy are not appropriate to reform of social sectors such as health. PMID- 17844936 TI - The World Health Organization, the drugs company, and the $10,000 funding offer. AB - The World Health Organization faces allegations that it attempted to secure a $10,000 donation from a pharmaceutical company by asking a patients' group to act as a covert channel for the funds, an arrangement that would break the WHO's own rules on accepting money from the pharmaceutical industry. The WHO denies attempts to bend its donation rules. PMID- 17844935 TI - Vietnam during economic transition: a tracer study of health service access and affordability. AB - For many decades, Vietnam had a well-structured public health service with extensive population coverage, with free care at government health facilities until 1989. Since then the country has been going through economic transition, including major changes to the health system. These include the reduction of financial support to public facilities and the introduction of user charges. Concern has been growing about the effect of these changes on access and affordability of health care, particularly for poor families. Using data from the Vietnam National Health Survey conducted in 2001-2002, the authors conducted a tracer study of people with diarrheal illness to examine equity in access to and use of health care and the financial burdens placed on patients in seeking care. The study found that children, the elderly, and the poorly educated were more likely to suffer from diarrhea; poor people often did not seek any care regardless of severity of illness, largely because they could not afford it. The opportunity cost due to lost income was also much greater for poor families. Several new policies have been developed in Vietnam to improve access to basic health care for the poor. However, the effects of such policies require close monitoring and remain to be evaluated. PMID- 17844937 TI - Industry-funded breast cancer trials show more positive results. AB - New research on pharmaceutical-industry sponsorship of clinical research in breast cancer shows that treatment trials funded by the industry are more likely to show positive results than studies sponsored by other sources. There are also major differences in trial design when drug companies are the funders. PMID- 17844938 TI - Technetium-99m-HMPAO SPECT cerebral blood flow alterations and quantitative EEG sequelae of daily cannabis use. PMID- 17844939 TI - Recognizing a mother's voice in the persistent vegetative state. AB - We studied an 8-year-old boy after a near-drowning left him in a vegetative state (VS) for 4 years before the study. Findings fulfilled all clinical criteria for the diagnosis of VS. The purpose of this study was to investigate whether there was significant differential activation of the brain in response to hearing his mother's voice compared with the voices of unknown women. The data were assessed using quantitative electric tomography (QEEGt), a technique that combines anatomical information of the brain by MRI with EEG patterns to estimate the sources of the EEG within the brain. We found significant differences for EEG frequencies from 14-58 Hz, with a peak at 33.2 Hz (gamma band). The 3D reconstruction showed that these statistical differences were localized in the lateral and posterior regions of the left hemisphere. No significant differences were found between unknown women vs. basal conditions. These results demonstrate recognition of the mother's voice and indicate high-level residual linguistic processing in a patient meeting clinical criteria for VS. These findings launch new ethical and practical implications for the management of VS patients. PMID- 17844940 TI - Reduced axon number in juvenile myoclonic epilepsy demonstrated by motor unit number estimation analysis. AB - Some conventional and quantitative EMG studies have already demonstrated a subclinical lower motor neuron involvement in juvenile myoclonic epilepsy (JME). Our aim was to investigate this subclinical involvement by using motor unit number estimation (MUNE) analysis with modified McComas' technique. We enrolled 75 consecutive JME patients and 26 normal controls. All subjects underwent motor and sensory nerve conduction studies, concentric needle EMG and MUNE analysis of the M. abductor pollicis brevis (APB) and M. tibialis anterior (TA). The clinical and EEG findings were evaluated to correlate with MUNE values. MUNE values of the APB (54+/-25) and TA (35+/-17) muscles were significantly lower in the JME group (p<0.001) when compared to the normal controls (109+/-24 and 80+/-26 for APB and TA muscles, respectively). Our findings show that anterior hom cells were subclinically affected in some JME patients, suggesting a shared background for both JME phenotype and grey matter disorganization in spinal cord. PMID- 17844941 TI - Transforming electrocortical mapping data into standardized common space. AB - Subdural grid electrodes are implanted routinely for the pre-surgical work up of epilepsy. While different approaches are available, many centers, including ours, visualize electrode locations by co-registering pre-operative 3-D MR images with post-implantation 3-D CT images. This method allows the determination of the electrode positions in relation to the individual patient's anatomy, but does not easily allow comparison across patients. The goal of this study was to develop and validate a method for transforming electrode positions derived from 3-D CT images into standardized space. We analyzed data from twelve patients with subdurally implanted electrodes. Volumetric CT and MRI images were co-registered and then normalized into common stereotactic space. Electrode locations were verified statistically by comparing distances between the anterior commissure and a representative sampling of 8 electrode sites per patient. Results confirm the accuracy of our co-registration method for comparing electrode locations across patients. PMID- 17844942 TI - The prognostic significance of interictal epileptiform activity in postoperative EEGs of patients with mesial temporal lobe epilepsy. AB - It has not been established whether electroencephalography (EEG) is a contributing factor in predicting the outcome of surgery for epilepsy. We conducted a prospective study on 26 patients (M/F 14/12, age: 33 +/- 7.5 years, range 19-48) with mesial temporal lobe epilepsy (MTLE) who were followed for 2 years after surgery and who underwent routine EEG recordings 5.6 +/- 3 months (range 3-12) postoperatively. Interictal epileptiform activity (IEA) on the EEG was compared in 17 seizure-free patients to 9 patients with recurrent seizures. The two groups were similar in gender, age, febrile convulsions, trauma, family history, seizure frequency prior to surgery, epilepsy duration and number of antiepileptic drugs. Following surgery, 17 study patients (65%) became seizure free; 9 (35%) had seizure recurrence. Post-operative EEG recordings showed IEA in 8/26 study patients (31%), 3 of whom were from the seizure-free group (3/17, 18%); 5 had seizure recurrence (5/9, 56%) (p=0.078). IEAs in postoperative EEGs were less frequently demonstrated in patients who were seizure free, but the presence of postoperative IEAs does not preclude successful surgical outcome. PMID- 17844943 TI - Gender specific processing of eye contact within the human medial temporal lobe. AB - Eye contact is a powerful social stimulus for human and non-human primates. However, it is unclear whether brain mechanisms that interpret eye contact are sensitive to gender. Here we show that human brain responses to eye contact are indeed gender specific. Recording event-related potentials directly from the medial temporal lobes, we found that eye contact elicited specific responses in men only when they saw female faces. Conversely, women responded specifically to eye contact only when they saw pictures of men. Thus, the human medial temporal lobes subserve specifically the processing of eye contact with persons of the opposite gender. PMID- 17844944 TI - nCPAP treatment of obstructive sleep apnea increases slow wave sleep in prefrontal EEG. AB - According to standard sleep stage scoring, sleep EEG is studied from the central area of parietal lobes. However, slow wave sleep (SWS) has been found to be more powerful in frontal areas in healthy subjects. Obstructive sleep apnea syndrome (OSAS) patients often suffer from functional disturbances in prefrontal lobes. We studied the effects of nasal Continuous Positive Airway Pressure (nCPAP) treatment on sleep EEG, and especially on SWS, in left prefrontal and central locations in 12 mild to moderate OSAS patients. Sleep EEG was recorded by polysomnography before treatment and after a 3 month nCPAP treatment period. Recordings were classified into sleep stages. No difference was found in SWS by central sleep stage scoring after the nCPAP treatment period, but in the prefrontal lobe all night S3 sleep stage increased during treatment. Furthermore, prefrontal SWS increased in the second and decreased in the fourth NREM period. There was more SWS in prefrontal areas both before and after nCPAP treatment, and SWS increased significantly more in prefrontal than central areas during treatment. Regarding only central sleep stage scoring, nCPAP treatment did not increase SWS significantly. Frontopolar recording of sleep EEG is useful in addition to central recordings in order to better evaluate the results of nCPAP treatment. PMID- 17844945 TI - QEEG prognostic value in acute stroke. AB - The objective of our study is to determine the predictive value of QEEG in patients suffering from an acute ischemic cerebral stroke. Twenty-eight patients were studied within the first 72 hours of clinical evolution of middle cerebral artery territory ischemic stroke. Thirty-seven QEEG recordings were obtained: 13 in the first 24 hours after cerebral stroke onset, 9 between 24-48 hours and 15 between 48-72 hours. Absolute Energies (AE) were the QEEG selected variables for statistical analysis: first, AE Z values were calculated using the Cuban QEEG norms, then the maximum and minimum AE Z values were selected within each frequency band and total power. The medians of the five neighboring Z values were also chosen. Regression models were estimated using the RANKIN scores as dependent variables and the selected QEEG variables as independent, then outcome predictions at hospital discharge and 3 months later were calculated. Percentages of concordance and errors between the estimated and real outcome scores were obtained. Alpha and theta AE were the best predictor for short-term outcome and delta AE for long-term outcome. We conclude that QEEG performed within the first 72 hours of ischemic stroke might be a powerful tool predicting short- and long term outcome. PMID- 17844946 TI - Source localization of triphasic waves: implications for the pathophysiological mechanism. AB - To investigate the current source location from the electroencephalograms (EEGs) of 12 patients who showed typical triphasic waves attributable to various causes, using the combination of a dipole source model and a distributed source model. The triphasic waves were explained by a single main dipole in 10 of the 12 patients, and 2 patients had two dipoles responsible for the triphasic waves. All the main dipoles had a radial orientation with respect to the frontal pole. The current density of the triphasic waves was distributed mainly in the bilateral medial frontal regions along the cingulate cortices. These findings suggest that current sources located in the medial frontal area are crucial for generating triphasic waves. The source localization may be useful for elucidating the pathophysiologic mechanism of generalized non-epileptic EEG activities, such as triphasic waves. PMID- 17844947 TI - Scalp-recorded auditory P300 event-related potentials in new-onset untreated temporal lobe epilepsy. AB - We studied scalp-recorded auditory event-related potentials (ERPs) of 30 untreated patients with new-onset temporal lobe epilepsy and 30 age- and sex matched normal controls. This study was designed to eliminate the effects of intractability of seizures and chronic use of antiepileptic drugs on P300 auditory ERPs. There were no statistically significant differences in both latency and amplitude of P300 between the two groups. Similar methods were also used to analyze component latencies and amplitudes of ERPs of 9 patients who had hippocampal sclerosis with comparison to control subjects. There were no statistically significant differences between these two groups as well. Our study evidently does not support temporal lobe sources of P300 scalp-recorded auditory ERPs. We also conclude that the scalp-recorded auditory ERPs procedure is not a useful tool to evaluate temporal lobe epilepsy. PMID- 17844948 TI - Complex partial status epilepticus in paraneoplastic limbic encephalitis. AB - Paraneoplastic limbic encephalitis (PLE) results from tumor-related autoimmune mediated inflammation and degeneration of the mesial temporal structures. Cognitive and behavioral changes and seizures occur in PLE. Seizures are an uncommon presenting symptom of PLE occurring in 6 of 50 patients in one series. We present a report of complex partial status epilepticus (CPSE) as the presentation of PLE with anti-neuronal antibodies and improvement in mental status following treatment of seizures. PMID- 17844949 TI - Multimodality imaging in a depressed patient with violent behavior and temporal lobe seizures. AB - Patients suffering from epilepsy commonly experience behavioral symptoms. Behavioral manifestations are especially prevalent in patients with seizures originating in the limbic system. This case report illustrates how an objective, multimodality work-up can guide the clinician in the diagnosis and the treatment of a patient with a complex presentation. After the discontinuation of some medications, the patient underwent a multimodality work-up that consisted of MRI, SPECT, and conventional and quantitative EEG (LORETA). In this case, the functional imaging studies showed a convergence of findings across the three modalities: MRI, SPECT and qEEG. Because of these findings, we supported more aggressive treatment of the seizure disorder. Ultimately this treatment resulted in resolution of the aggression and the depression. In summary, when applied routinely, a comprehensive, systematic, diagnostic approach will minimize treatment false starts and failures, may reduce costs, and also, potentially decrease the severity and the duration of symptoms. PMID- 17844950 TI - [Etiopathogenia of the epistaxis admitted by emergencies service. Analysis and considerations in 250 consecutive patients]. AB - Epistaxis represent a relatively common symptom in the hospitalary Emergencies Services. In our casuistry of 250 consecutive patients assisted and admitted because of that cause in 2 different hospitals of the region between 1996 and 2005, we have noticed the presence of one or more base pathologies or risk factors in originate most of them which could the nose bleeding. These causes are analysed beside the location of the epistaxis and the different treatment options that were used until its resolution. PMID- 17844951 TI - [Maxillary sinus hypoplasia masquerading a chronic sinusitis]. AB - Maxillary sinus hypoplasia is a relatively uncommon clinical condition that may be misdiagnosed as chronic sinusitis or neoplasm by otolaryngologist. We report an unilateral clinical case of this entity confirmed by CT and a short literature review is performed at this respect. PMID- 17844953 TI - [Upper dyspnea in nursing baby. Diagnostic and clinic treatment]. AB - We detail here the clinical case of a 22 month old child who was referred to our department because of recurring episodes of upper dyspnea and barking cough since he was 3 months old. The Pediatric Department suspected laryngeal stenosis or laryngomalacia and asked for confirmation of this. The ENT examination including nasofibrolaryngoscopy was normal. A computerised axial tomography (CAT) was carried out, as well as a magnetic resonance of the neck, both eliminating possible pathologies. Having tried several treatments, we prescribed empirical treatment with proton pump inhibitors, and to our surprise the improvement was spectacular. We have carried out a review of literature about gastroesophageal reflux, its manifestations, diagnosis and treatment. PMID- 17844952 TI - [Nasal T lymphoma]. AB - Nasal T lymphoma constitute a type of lymphoproliferative very infrequent symdrome. One of the fondamental problems it presents to bring a high probability of survival obtain a precocious diagnose. It is due that it originates inespecific histologic lesions, and to its clinic. Only the close cooperation between the otorhinolaryngologist and the anatomopathologist can arrive to obtain a very speedy diagnose and in that way the possibility of a correct treatment, because newly treatments appear, to which this type of disease every day better respond. We present the cases of nasal T lymphomas diagnosticated in the ORL Service of the Toledo area during 15 years, their symptomotology, treatment, evolution and survival. Besides a up to date bibliographic revision on this controversial syndrome. PMID- 17844955 TI - [Frontoethmoidal mucocele. Diagnosis and treatment in 7 cases]. AB - Mucocele has its origin by blockage of the paranasal sinuses ostium with mucinous retention inside, sometimes purulent (mucopiocele), and progressive slimming with gradual destruction on the bone walls. We report an own review of 7 patients with diagnosis of frontoethmoidal mucocele, 4 men and 3 women, 50-years average. The oftalmologic clinical symptoms (diplopia, exoftalmos and the eyeball movement restrictiv) were the most frequentjointly to cefalea. The kind of surgery that we have performed, in 6 of 7 cases, was FES with marsupialization (4 times) and external ethmoidectomy (2). We have performes a literature review at this respect. PMID- 17844954 TI - [Sinonasal mucosal melanoma]. AB - Mucosal melanomas of the nasal cavity and paranasal sinuses are rare and agresive neoplasms and carries a bad prognosis. The diagnosis may require confirmatory immunohistochemical stains (S-100 protein, HMB-45, vimentin and cytokeratine). The clinical records of 6 patients with the diagnosis of sinonasal melanomas between 1991 and 2005 were retrospectively reviewed. The mean age was 70 years (range 51 to 83 years), there were 2 men and 4 women. Surgery was performed in four patients, adjuvant radiation therapy was used in one patient after local recurrence and chemotherapy in three patients. Three of four patients (75%) had a recurrence after previous treatment (surgery). The actuarial disease-free survival for this group of 6 is 33.3% (2 of 6). Mucosal melanoma of the head and neck remains a difficult disease to treat, with high locoregional recurrence rates and poor prognosis. PMID- 17844956 TI - [Frontal pyomucocele]. AB - Mucoceles are strictly defined as chronic, expanding, mucosa-lined lesions of the frontal sinus and containing insipissated secretion. We present a 48-years-old female who complains right periorbital and frontal swelling of approximately 1,5 years duration. Radiological and exploratory findings confirm the diagnosis of infected mucocele (pyomucocele). Under general anesthesia an endoscopic sinus surgery was performed. One year later, the patient is alive and well with no evidence of primary disease. PMID- 17844957 TI - [Papilar thyroid carcinoma. An unusual clinic]. AB - The Papillary carcinoma is the most frequent neoplasic tumour of the thyroid gland. It accounts for 70-75% of all malignant thyroid tumours. In 80-90% of cases it presents as a slow-growing single thyroid node. Nevertheless, in 10-26% of cases, the initial presentation is a lateral neck mass without palpable thyroid mass. We present the case of a 67 year- old patient who attended to the ENT out-patient clinic with a lateral neck mass which had been growing slowly over the course of number of years. PMID- 17844958 TI - [Cervical osteophytosis as cause of dysphagia. Forestier-Rotes Querol's disease]. AB - The so called Forestier-Rotes Querol's disease or diffuse idiopathic skeletal hyperostosis can affect the neck caused by osteophytos and ossification calcification of the vertebral ligaments. The location in that region can produce dysphagia or hoarseness, among other symptoms, so that the patient can assist or be sent to ENT valoration. We are reporting a case of this pathology which was diagnosed in our hospital. Finally a bibliographic review is performed. PMID- 17844959 TI - [Schwannomas of the lingual nerve]. AB - Schwanomas in extracranial head and neck region are an uncommon tumour, but when refered to its origin in the parasympathetic nerve fibers are extremely rare. We describe a case of schwanoma of the right submandibular gland originating from the parasympathetic branch of the lingual nerve, and we discuss about the clinical, diagnostic and therapeutic aspects of this rare tumour and a literature review of the recent cases. PMID- 17844960 TI - [Facial solitary infantile myofibromatosis]. AB - Infantile myofibromatosis is an infrequent and benign pathology. It can turn up as a single or multiple tumour. The prognosis depends on visceral involvement. The differential diagnosis includes some pathologies with similar clinical appearance but worse prognosis. We report a 6 months old boy that arrived to our office refering a short progress and fast growth facial mass. The diagnosis after hystologic study and immunohistochemistry was infantile myofibromatosis. After more than a year of monitoring he is actually disease free. PMID- 17844961 TI - Stereopsis and motion parallax. PMID- 17844962 TI - Cueing attention by relative motion in the periphery of the visual field. AB - Sudden changes of visual stimulation attract attention. The observer's body motion generates retinal-flow field patterns containing information about his/her own speed and trajectory and relative motion of other objects. We investigated the effectiveness of relative motion as an attentional cue and compared it with conventional cueing by appearance of a frame in the far periphery of the visual field. In a group of ten subjects, contrast thresholds for the perception of static Gabor grating orientation [four alternative non-forced-choice (4ANFC)] task were determined at 20 degrees, 30 degrees, 40 degrees, and 60 degrees eccentricity. Subsequently, near-threshold discrimination performance of Gabor pattern orientation without versus with a ring-shaped cue was measured at the same positions. The same Gabor patterns were then presented embedded in a random dot flow field, and uncued discrimination performance was compared with performance after presentation of a relative-motion cue (RMC), ie a small random dot field with motion in the opposite direction of the flow field. Both the conventional ring cue and the RMC induced significantly increased discrimination performance at all test locations. With the parameters chosen for this study, the RMC was slightly less effective than the conventional cue, but its effects were somewhat more pronounced in the far periphery of the visual field. Thus, relative motion is a powerful cue to attract attention to peripheral visual objects and improves performance as effectively as a conventional ring cue. The findings have practical relevance for everyday life, in particular for tasks like driving and navigation. PMID- 17844963 TI - Accuracy of head orientation perception in triadic situations: experiment in a virtual environment. AB - Research has revealed high accuracy in the perception of gaze in dyadic (sender- receiver) situations. Triadic situations differ from these in that an observer has to report where a sender is looking, not relative to himself. This is more difficult owing to the less favourable position of the observer. The effect of the position of the observer on the accuracy of the identification of the sender's looking direction is relatively unexplored. Here, we investigate this, focusing exclusively on head orientation. We used a virtual environment to ensure good stimulus control. We found a mean angular error close to 5 degrees. A higher observer viewpoint results in more accurate identification. Similarly, a viewpoint with a smaller angle to the sender's midsagittal plane leads to an improvement in identification performance. Also, we found an effect of underestimation of the error in horizontal direction, similar to findings for dyadic situations. PMID- 17844964 TI - The visual discrimination of bending. AB - The sensitivity of observers to nonrigid bending was evaluated in two experiments. In both experiments, observers were required to discriminate on any given trial which of two bending rods was more elastic. In experiment 1, both rods bent within the same oriented plane, and bent either in a frontoparallel plane or bent in depth. In experiment 2, the two rods within any given trial bent in different, randomly chosen orientations in depth. The results of both experiments revealed that human observers are sensitive to, and can reliably detect, relatively small differences in bending (the average Weber fraction across experiments 1 and 2 was 9.0%). The performance of the human observers was compared to that of models that based their elasticity judgments upon either static projected curvature or mean and maximal projected speed. Despite the fact that all of the observers reported compelling 3-D perceptions of bending in depth, their judgments were both qualitatively and quantitatively consistent with the performance of the models. This similarity suggests that relatively straightforward information about the elasticity of simple bending objects is available in projected retinal images. PMID- 17844965 TI - Perceived depth in the 'sieve effect' and exclusive binocular rivalry. AB - An impression of a surface seen through holes is created when one fuses dichoptic pairs of discs, with one member of each pair black and the other member white. This is referred to as the 'sieve effect'. The stimulus contains no positional disparities. Howard (1995, Perception 24 67-74) noted qualitatively that the sieve effect occurs when the rivalrous regions are within the range of sizes, contrasts, and relative sizes where exclusive rivalry occurs, rather than binocular lustre, stimulus combination, or dominant rivalry. This suggests that perceived depth in the sieve effect should be at a maximum when exclusive rivalry is most prominent. We used a disparity depth probe to measure the magnitude of perceived depth in the sieve effect as a function of the sizes, contrasts, and relative sizes of the rivalrous regions. We also measured the rate of exclusive rivalry of the same stimuli under the same conditions. Perceived depth and the rate of exclusive rivalry were affected in the same way by each of the three variables. Furthermore, perceived depth and the rate of exclusive rivalry were affected in the same way by changes in vergence angle, although the configuration of the stimulus surface was held constant. These findings confirm the hypothesis that the sieve effect is correlated with the incidence of exclusive rivalry. PMID- 17844966 TI - The modulation of haptic line bisection by a visual illusion and optokinetic stimulation. AB - Research has shown that a variety of different sensory manipulations, including visual illusions, transcutaneous nerve stimulation, vestibular caloric stimulation, optokinetic stimulation, and prism adaptation, can all influence people's performance on spatial tasks such as line bisection. It has been suggested that these manipulations may act upon the 'higher-order' levels of representation used to code spatial information. We investigated whether we could influence haptic line bisection in normal participants crossmodally by varying the visual background that participants viewed. In experiment 1, participants haptically bisected wooden rods while looking at a variant of the Oppel - Kundt visual illusion. Haptic-bisection judgments were influenced by the orientation of the visual illusion (in line with previous unimodal visual findings). In experiment 2, haptic-bisection judgments were also influenced by the presence of a leftward or rightward moving visual background. In experiments 3 and 4, the position of the to-be-bisected stimuli was varied with respect to the participant's body midline. The results confirmed an effect of optokinetic stimulation, but not of the Oppel -Kundt illusion, on participants' tactile bisection errors, suggesting that the two manipulations might differentially affect haptic processing. Taken together, these results suggest that the 'higher order' levels of spatial representation upon which perceptual judgments and/or motor responses are made may have multisensory or amodal characteristics. PMID- 17844967 TI - A variant of the anomalous motion illusion based upon contrast and visual latency. AB - We examined a variant of the anomalous motion illusion. In a series of experiments, we ascertained luminance contrast to be the critical factor. Low contrast random dots showed longer latency than high-contrast ones, irrespective of whether they were dark or light (experiments 1 -3). We conjecture that this illusion may share the same mechanism with the Hess effect, which is characterised by visual delay of a low-contrast, dark stimulus in a moving situation. Since the Hess effect is known as the monocular version of the Pulfrich effect, we examined whether illusory motion in depth could be observed if a high-contrast pattern was projected to one eye and the same pattern of low contrast was presented to the other eye, and they were binocularly fused and swayed horizontally. Observers then reported illusory motion in depth when the low-contrast pattern was dark, but they did not when it was bright (experiment 4). Possible explanations of this inconsistency are discussed. PMID- 17844968 TI - Grouping effects in flash-induced perceptual fading. AB - We show that the flash-induced fading effect can be influenced by grouping based on colour and shape similarity. In flash-induced fading, peripherally presented elements perceptually disappear after a flash has been presented around or next to the element(s) (Kanai and Kamitani, 2003 Journal of Cognitive Neuroscience 15 664-672). In the present study, two elements (which could either be similar or different in both colour and shape) were presented at an eccentricity of 2.6 degrees from a fixation cross. After 2 s, a short flash (40 ms) was presented around one of the elements. The two elements remained on the screen for 2.5 s after the flash. We found a higher percentage of mutual perceptual disappearance when the two elements were similar in colour or in shape. These results converge with other findings showing that perceptual fading phenomena are influenced by effects of perceptual grouping. This indicates that, besides low-level adaptation, more global processes play a part in perceptual fading as well and should thus be taken into account in giving a full explanation of perceptual fading in general. PMID- 17844969 TI - The flash-lag effect during illusory chopstick rotation. AB - In the 'flash-lag' effect, a static object that is briefly flashed next to a moving object appears to lag behind the moving object. A flash was put up next to an intersection that appeared to be moving clockwise along a circular path but was actually moving counterclockwise [the chopstick illusion; Anstis, 1990, in AI and the Eye Eds A Blake, T Troscianko (London: John Wiley) pp 105 117; 2003, in Levels of Perception Eds L Harris, M Jenkin (New York: Springer) pp 90 93]. As a result, the flash appeared displaced clockwise. This was appropriate to the physical, not the subjective, direction of rotation, and it suggests that the flash-lag illusion occurs early in the visual system, before motion signals are parsed into moving objects. PMID- 17844970 TI - Relationship between frames of reference and mirror-image reversals. AB - The mirror puzzle related to the perception of mirror images as left-right reversed can be more fully understood by considering an extended problem that includes also the perception of mirror images that are not left-right reversed. The purpose of the present study is to clarify the physical aspect of this extended problem logically and parsimoniously. Separate use of the intrinsic frame of reference that belongs to the object and one that belongs to its mirror image always leads to the perception of left-right reversal when the object has left-right asymmetry; on the other hand, the perception of left-right nonreversal is always due to the application of a common frame of reference to the object and its mirror image. PMID- 17844971 TI - Differences in attentional involvement underlying the perception of distinctive and typical faces. AB - Differences in human faces can be evaluated along a continuum that ranges from 'distinctive' to 'typical.' We examined processing differences between distinctive and typical faces by two attentional tasks that induce attentional blink (AB). Given that AB is believed to reflect temporal or capacity limits of attention, stimuli that survive AB are believed to be associated with greater processing efficiency. In a change-detection task, participants were required to detect changes in the two pairs of faces that were presented in rapid succession. Changes involving the distinctive face of a pair were more likely to be detected than those involving a typical face. In a face-identification task, distinctive faces embedded in a rapid serial visual presentation (RSVP) stream were identified with a greater accuracy than typical faces. Together, our results suggest that distinctive faces are associated with greater processing efficiency and may be explained in terms of perceptual salience, a stimulus dimension known to attract attention. PMID- 17844972 TI - Isovist analysis captures properties of space relevant for locomotion and experience. AB - In a series of exploratory experiments we investigated interrelations between structure and shape of architectural indoor spaces on the one hand, and affective experience and navigation behaviour on the other hand. For this, isovist-based descriptions of 16 virtual indoor scenes were correlated with behavioural data from the experimental tasks. For all tasks-two active navigation tasks and an introspective appraisal of experiential qualities--strong correlations between subjects' behaviour and a small set of quantitative measurands derived from the isovists were found. The outcomes suggest that isovist analysis captures behaviourally relevant properties of space and is therefore a promising general means for predicting central experiential qualities of architecture and navigation behaviour. PMID- 17844973 TI - Dyslexia: sensory deficits or inattention? AB - An important question in regard to dyslexia is whether or not this condition is the result of sensory deficits. A number of studies have indeed found sensory deficiencies in dyslexic readers. However, it has been proposed that these are due simply to inattention. If so, this would be expected to produce either (i) a general reduction or (ii) random reductions in performance. On the basis of published data, it seems that neither of these is in fact the case. Rather the data indicate reproducible non-random patterns of deficiencies with regard to stimulus conditions. The stimulus specificity of the deficits represents, therefore, an important issue which needs to be addressed by any attempt to account for the sensory deficiencies of dyslexic readers in terms of inattention. PMID- 17844974 TI - The effect of brief auditory stimuli on visual apparent motion. AB - When two discrete stimuli are presented in rapid succession, observers typically report a movement of the lead stimulus toward the lag stimulus. The object of this study was to investigate crossmodal effects of irrelevant sounds on this illusion of visual apparent motion. Observers were presented with two visual stimuli that were temporally separated by interstimulus onset intervals from 0 to 350 ms. After each trial, observers classified their impression of the stimuli using a categorisation system. The presentation of short sounds intervening between the visual stimuli facilitated the impression of apparent motion relative to baseline (visual stimuli without sounds), whereas sounds presented before the first and after the second visual stimulus as well as simultaneously presented sounds reduced the motion impression. The results demonstrate an effect of the temporal structure of irrelevant sounds on visual apparent motion that is discussed in light of a related multisensory phenomenon, 'temporal ventriloquism', on the assumption that sounds can attract lights in the temporal dimension. PMID- 17844975 TI - Last but not least. AB - A central tenet of Gestalt psychology is that the visual scene can be separated into figure and ground. The two illusions we present demonstrate that Gestalt processes can group spatial contrast information that cuts across the figure/ground separation. This finding suggests that visual processes that organise the visual scene do not necessarily require structural segmentation as their primary input. PMID- 17844976 TI - International Classification of Functioning, Disability and Health. PMID- 17844977 TI - A survey of occupational therapists in Canada about their knowledge and use of the ICF. AB - BACKGROUND: The current impact of the International Classification of Functioning, Disability and Health (ICF) on the field of occupational therapy within Canada is unknown. PURPOSE: To survey occupational therapists in Canada about their knowledge, use of and suggestions for education about the ICF. METHOD: Mixed methods design included (i) an online survey, with data analyzed using quantitative methods; and (ii) semi-structured interviews with a purposeful sample of 10 therapists, using content analysis. RESULTS: The online survey was completed by 587 occupational therapists (17.6% return). Four hundred and ten respondents (70.0%) indicated some ICF knowledge, and 121 of those individuals (29.5%) reported using it in practice. Interview participants suggested resources, perceived meaning and investment factors impact ICF knowledge. Suggested uses include frameworks and interprofessional collaboration, while ideas for education involve meaningful and accessible formats. PRACTICE IMPLICATIONS: The ICF may be useful to occupational therapists in different settings if it fulfills a meaningful purpose and fits with practice models. PMID- 17844978 TI - Comparing the Disability Creation Process and International Classification of Functioning, Disability and Health models. AB - BACKGROUND: The conceptualisation of participation is important for both clinicians and researchers. Purpose. Analyse and compare two conceptual models, the Disability Creation Process (DCP) and the International Classification of Functioning, Disability and Health (ICF), with particular emphasis on the participation component. METHOD: Conceptual comparative analysis of the DCP and ICF models focused on participation. RESULTS: We found more differences than similarities between the DCP and ICF models. Similarities concerned approaches, objectives, elements of the models' components, and, to some extent, the participation component itself Differences were mainly in the underlying models, conceptualisation of components including participation, and the measurement tools of participation. PRACTICE IMPLICATIONS: Based on the results of this conceptual comparison, occupational therapists working in clinical and research settings are encouraged to consider using the DCP, which is an excellent model to choose in regard to participation. Empirical studies are still needed to clarify the concept of participation. PMID- 17844979 TI - Environmental factors and their role in community integration after spinal cord injury. AB - BACKGROUND: The International Classification of Functioning, Disability and Health (ICF) model presents an opportunity to better understand previously neglected longterm social outcomes after traumatic spinal cord injury (SCI), especially the experience of participation. PURPOSE: The study explored the relationship between perceived environmental barriers and perceived community integration (a participation proxy) in a sample of adults with traumatic SCI. METHODS: The study interviewed African American and White women and men (n = 136) who had lived with SCI for an average of 11.5 years. RESULTS: Participants reported environmental barriers at twice the level indicated by previous studies; the natural environment and the policies of government were the most problematic. Levels of community integration were also high. Data suggest a significant relationship (p < .01) between perceived environmental barriers and community integration for adults with SCI, providing support for the ICF model. IMPLICATIONS: Improved measures and more sophisticated concepts and theories are needed to explicate the relationship between environmental factors and participation concepts in the ICE With respect to practice, occupational therapists need to be aware that removal of environmental barriers is only a first step in the more complex effort to facilitate optimal community integration after SCI. PMID- 17844980 TI - Validating the potential of the International Classification of Functioning, Disability and Health to identify barriers to and facilitators of consumer participation. AB - BACKGROUND: Occupational therapists need tools to identify barriers and facilitators to participation in societal roles. PURPOSE: The purpose of this study was to examine the potential of the International Classification of Functioning, Disability and Health (ICF) two-level classification for use in occupational therapy. METHODS: A secondary analysis of an existing dataset was conducted to identify participation barriers and facilitators that mapped to the ICF and those that did not. RESULTS: A broad range of factors was captured across the components of the ICF. Findings also revealed enabling and disabling factors that were not evident in the ICF. PRACTICE IMPLICATIONS: The ICF can support the identification of a broad range of external barriers and facilitators relevant to participation and of interest to occupational therapy. However, therapists must use other strategies to gain a comprehensive understanding of the nature, extent and consequences of barriers and facilitators that may exist in a given PMID- 17844981 TI - Does the Comprehensive ICF Core Set for rheumatoid arthritis capture occupational therapy practice? A content-validity study. AB - BACKGROUND: The ICF Core Sets for rheumatoid arthritis (RA) constitute an application of the International Classification of Functioning, Disability and Health (ICF). PURPOSE: To explore whether the ICF Core Sets for RA include the areas of functioning and environmental factors that are typically treated by occupational therapists in their clinical everyday practice with clients with RA. METHODS: In a three-round survey occupational therapists were asked about their intervention goals when treating clients with RA. The identified goals were grouped into goal classes that were then linked to the ICF. RESULTS: 41 occupational therapists in nine countries named 533 intervention goals that were grouped into 48 goal classes and then linked to ICF categories of all ICF components. The goal classes self-confidence, relaxation and psycho-social well being are not represented in the Comprehensive ICF Core Set for RA. CONCLUSION: The validity of the ICF Core Set for RA from the perspective of occupational therapists was largely confirmed. PMID- 17844982 TI - A comparison of the International Classification of Functioning, Disability, and Health to the disability tax credit. AB - BACKGROUND: The Disability Tax Credit (DTC) Certification is an assessment tool used to provide Canadians with disability tax relief The International Classification of Functioning, Disability and Health (ICF) provides a universal framework for defining disability. PURPOSE: The purpose of this study was to evaluate the DTC and familiarize occupational therapists with the process of mapping measures to the ICF classification system. METHOD: Concepts within the DTC were identified and mapped to appropriate ICF codes (Cieza et al., 2005). RESULTS: The DTC was linked to 45 unique ICF codes (16 Body Functions, 19 Activities and Participation, and 8 Environmental Factors). IMPLICATIONS: The DTC encompasses various domains of the ICF; however, there is no consideration of Personal Factors, Body Structures, and key aspects of Activities and Participation. Refining the DTC to address these aspects will provide an opportunity for fair and just determinations for those who experience disability. PMID- 17844983 TI - Shopping the pyramid. A guide to the government's latest nutrition advice. PMID- 17844984 TI - Who's the weaker sex? PMID- 17844985 TI - A fever's deadly path. The worst outbreak of Marburg fever isn't reined in yet. PMID- 17844986 TI - Rules to live (and die) by. PMID- 17844988 TI - The Pope and the surgeon. PMID- 17844987 TI - How we drive our jobs away. PMID- 17844989 TI - Reactivity of anthocyanins and pyranoanthocyanins. Studies on aromatic hydrogen deuterium exchange reactions in methanol. AB - Reactivity studies involving anthocyanin structures and their equilibrium forms will lead to better understanding of the properties of these antioxidants. Hydrogen-deuterium (H --> D) exchange reactions at various sites of the 3 glucosides of delphinidin (1), petunidin (2), malvidin (3), and the corresponding 3-glucosides of carboxypyranodelphinidin (4), carboxypyranopetunidin (5), carboxypyranomalvidin (6), and the flavonol quercetin 3-O-(6-alpha rhamnopyranosyl-beta-glucopyranoside)(7) have been examined at room temperature in pure CD 3OD and in CD 3OD acidified with CF 3CO 2D. The H --> D exchange rate constants of H-6 and H-8 of 2 determined from (1)H NMR integration data were found to be independent upon pigment concentration (up to 4 x 10 (-2) M) and trifluoroactic acid concentration (0-15%, v/v), respectively. This suggest that these reactions follow first-order kinetics and unexpectedly to be independent of the acid concentration. H-6 and H-8 of the flavylium cation A-rings of 1- 3, and in the corresponding hydrogens of the hemiketal forms, exchanged with half-lives of approximately 100 h ( 1) and approximately 50 h ( 2 and 3), respectively. The pyranoanthocyanins (4-6) experienced no H --> D exchange for the analogous hydrogens, but H --> D exchange of H-beta (H-4)(t 1/2 approximately 25 h) for these compounds was observed. Only H-8 underwent significant H --> D exchange in 7. It is concluded that a stabilization of the sigma-complexes, assumed to be the intermediates in the reactions, takes place for the common anthocyanins (1-3) contrary to the pyranoanthocyanins (4-6). PMID- 17844990 TI - Free galactose content in selected fresh fruits and vegetables and soy beverages. AB - The free galactose content was determined in three soy beverages, and 34 selected fruits and vegetables purchased at different times of the year and/or local markets in British Columbia, Canada. The objective of the work was to provide additional information on the free galactose content of foods to assist individuals with galactosemia in making dietary decisions. Free galactose contents in the selected plant materials ranged from 2.0 +/- 0.1 mg/100 g in red potato to 39.7 +/- 1.9 mg/100 g in red pepper. Different time of the season, variety, and storage of the product affected the free galactose contents in most of the plant materials measured in this study. Free galactose levels in kiwi, green seedless grapes, and bell peppers were found to be higher than previous reports, whereas the amount of free galactose in three varieties of tomatoes was significantly lower than previously reported. An evaluation of the change of galactose in Roma tomatoes during ripening showed that free galactose levels increased linearly over time, and storage at 4 degrees C significantly increased free galactose levels in tomatoes. Soy beverages made from soy protein isolate contained less free galactose (1.3 +/- 0.2 mg /100 g) compared to the samples made from whole soybeans (4.8 +/- 1.9 and 5.3 +/- 1.7 mg/ 100 g). This study provides additional information on the range of free galactose in fruits and vegetables which will allow individuals with galactosemia to make more informed dietary choices. PMID- 17844991 TI - Resveratrol inhibits the activity of equine neutrophil myeloperoxidase by a direct interaction with the enzyme. AB - Resveratrol is a polyphenolic antioxidant present in beverage and food known for its multiple protective effects. We report the inhibitory effects of resveratrol on equine myeloperoxidase (MPO), a hemic peroxidase present in the granules of the neutrophils involved in the inflammatory response. Resveratrol inhibited the production of reactive oxygen species (ROS) by stimulated equine neutrophils by acting as a direct scavenger of the ROS released by the cells but did not modify the degranulation of the stimulated neutrophils as the amounts of released MPO were unchanged. Resveratrol strongly inhibited the chlorination, oxidation, and nitration activities of MPO in a dose-dependent manner. By an original technique of specific immunological extraction followed by enzymatic detection (SIEFED), we demonstrated that resveratrol inhibited the peroxidasic activity of the MPO measured by a direct interaction such as the fixation of resveratrol on the enzyme. The observation of a decrease of the accumulation of compound II suggested that resveratrol acts as an electron donor for MPO reduction. PMID- 17844992 TI - Boldenone, boldione, and milk replacers in the diet of veal calves: the effects of phytosterol content on the urinary excretion of boldenone metabolites. AB - Twenty-six veal calves were split into two groups and fed two milk replacers with a different content of phytosterols for 26 days; then, 14 calves (7 animals from each diet) were kept as controls and 12 calves (6 per diet) received daily, per os, a combination of 17beta-boldenone (17beta-Bol) and androsta-1,4-dien-3,17 dione (ADD) for 38 days. The urinary elimination of 17 alpha-/17beta-boldenone conjugates (17 alpha/beta-Bol) and androsta-1,4-dien-3,17-dione (ADD) was followed by liquid chromatography-tandem mass spectrometry from all of the animals until slaughtering. In urine from treated animals, 17 alpha-Bol concentrations, despite a great variability, were greater than 17beta-Bol, both detected always as conjugates. At days 1, 2, and 3, the mean urine concentration of 17 alpha-Bol was higher than 12 ng/mL. A remarkable decrease was observed during the following days, but the 17 alpha-Bol concentration was still higher than the attention level of 2 ng/mL in 58% of the samples; the concentration of 17beta-Bol was around the action level of 1 ng/mL; two days after treatment withdrawal, no 17beta-Bol was detected in the urine. In urine from control animals, the 17 alpha-Bol concentration was strictly related to the phytosterol content of the diet, while, in urine from treated animals, the much higher 17 alpha-Bol levels were not modified by the production from diet precursors. The results confirmed that a 17 alpha-Bol level higher than 2 ng/mL should be considered as evidence of suspected illegal treatment and that the urinary excretion of 17beta-Bol is due to exogenous administration of 17beta-Bol. The discontinuous rate of elimination of both 17 alpha- and 17beta-Bol, despite the daily administration of 17beta-Bol plus ADD, indicates the necessity for further research to detect other urinary boldenone metabolites to strength surveillance strategy. PMID- 17844993 TI - Antimicrobial compounds from the Australian desert plant Eremophila neglecta. AB - A crude extract from the Australian desert plant Eremophila neglecta has recently been shown to possess antibacterial activity in a survey of candidate plants that may bear novel antimicrobial compounds. Bioassay-directed fractionation of the Et(2)O extract of E. neglecta using a broth microdilution assay led to the isolation of three new serrulatane-type diterpenoids, 2,19-diacetoxy-8 hydroxyserrulat-14-ene (2), 8,19-dihydroxyserrulat-14-ene (3), and 8 hydroxyserrulat-14-en-19-oic acid (4), and a known o-naphthoquinone commonly referred to as biflorin (5). The structures of 2-5 were determined using 1D and 2D NMR, FTIR, and high-resolution mass spectrometry. Compounds 3-5 showed antimicrobial activity against Gram-positive bacteria including Staphylococcus aureus, Streptococcus pyogenes, and S. pneumoniae. The minimum inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs) ranged from 6.5 to 101.6 microM and 12.7 to 202.9 microM, respectively. No activity was observed for these compounds against Gram-negative bacteria. PMID- 17844995 TI - Cardenolides from Saussurea stella with cytotoxicity toward cancer cells. AB - Three new cardenolides, 3-O-beta-D-fucopyranosylstrophanthidin (1), 3-O-beta-D quinovopyranosylperiplogenin (2), and 3-O-beta-D-glucopyranosyl-(1 --> 4)-alpha- l-rhamnopyranosylcannogenin (3), together with seven known cardenolides (4- 10), were isolated from a cytotoxic ethanol extract of the whole dried plants of Saussurea stella. The structures of these compounds were established by spectroscopic and chemical methods. When the cytotoxicity of compounds 2- 10 toward Bel-7402 human hepatoma cells and BGC-823 human gastric cancer cells was evaluated, all compounds showed IC 50 values of <1 microM for both cell lines. This is the first report of cardenolides occurring in a species of the family Asteraceae. PMID- 17844994 TI - Benzochromenones from the marine crinoid Comantheria rotula inhibit hypoxia inducible factor-1 (HIF-1) in cell-based reporter assays and differentially suppress the growth of certain tumor cell lines. AB - Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that promotes tumor cell adaptation and survival under hypoxic conditions. HIF-1 is currently recognized as an important molecular target for anticancer drug discovery. The National Cancer Institute open repository of marine invertebrates and algae lipid extracts was evaluated using a T47D breast tumor cell-based reporter assay for HIF-1 inhibitory activity. Bioassay-guided fractionation of an active extract from a crinoid Comantheria rotula yielded seven benzo[g]chromen-4-one and benzo[h]chromen-4-one pigments (1-7). The structures of the new benzo[g]chromenone dimer 9,9'-oxybis-neocomantherin (1) and another new natural pigment 5 were deduced from spectroscopic and spectrometric data. The crinoid pigments significantly inhibited both hypoxia-induced and iron chelator-induced HIF-1 luciferase reporter activity in breast and prostate tumor cells. However, inhibition of HIF-1 in the reporter assay did not translate into a significant decrease in the expression of the downstream HIF-1 target, secreted vascular endothelial growth factor (VEGF). Compound 1 was found to inhibit tumor cell growth in the NCI 60-cell line panel (GI(50) values of 1.6-18.2 microM), and compound 6 produced a unique pattern of tumor cell growth suppression. Five cell lines from different organs were hypersensitive to 6 (GI(50) values of 0.29-0.62 microM), and three others were moderately sensitive (GI(50) values of 2.2-5.1 microM), while the GI(50) values for most other cell lines ranged from 20 to 47 microM. Crinoid benzo[g]chromenones were also found to scavenge radicals in a modified DPPH assay. PMID- 17844996 TI - Antimalarial and antituberculous poly-O-acylated jatrophane diterpenoids from Pedilanthus tithymaloides. AB - Six new poly-O-acylated jatrophane diterpenes (1- 6) have been isolated along with five known compounds from the white latex of Pedilanthus tithymaloides. The structural identification was accomplished on the basis of 2D NMR and MS investigations. Some of these highly oxygenated jatrophane diterpenes possess a rare O-acetyl enol moiety. Compounds 1 and 3- 5 showed antiplasmodial activity with IC(50) values of 3.4-4.4 microg/mL and antimycobacterial activity against Mycobacterium tuberculosis with minimum inhibition concentration (MIC) values ranging from 12.5 to 100 microg/mL. PMID- 17844997 TI - Total synthesis of xanthohumol. AB - The total synthesis of xanthohumol (1) was accomplished in 10% overall yield from phloracetophenone after six steps. Insertion of a prenyl group onto the aryl ring was achieved by a para-Claisen rearrangement after using a Mitsunobu reaction to establish the key prenyl ether precursor. A Claisen-Schmidt condensation was deployed to construct the chalcone scaffold followed by removal of MOM protecting groups under acidic conditions that were optimized to prevent concomitant cyclization to the flavone. PMID- 17844998 TI - Marmycins A and B, cytotoxic pentacyclic C-glycosides from a marine sediment derived actinomycete related to the genus Streptomyces. AB - Two new cytotoxic quinones of the angucycline class, marmycins A and B ( 1, 2), were isolated from the culture broth of a marine sediment-derived actinomycete related to the genus Streptomyces. The gross structures and absolute configurations of both compounds were determined by spectroscopic and crystallographic methods. Marmycin A ( 1) displayed significant cytotoxicity against several cancer cell lines, some at nanomolar concentrations; while compound 2, a chloro analogue of 1, was less potent. For marmycin A ( 1), tumor cell cytotoxicity appeared to coincide with induction of modest apoptosis and arrest in the G1 phase of the cell cycle. PMID- 17844999 TI - Macrolactin is the polyketide biosynthesis product of the pks2 cluster of Bacillus amyloliquefaciens FZB42. AB - In the genome of Bacillus amyloliquefaciens FZB42, three operons pks1, pks2, and pks3 were identified which encode the biosynthesis of polyketides. pks1 and pks3 have been attributed to the production of bacillaene and difficidin/oxydifficidin, respectively, while the pks2 product remained hitherto unknown. Mass spectrometric analysis of the culture filtrates of the wild-type B. amyloliquefaciens FZB42 and mutants revealed pks2-specific metabolites. By combination of the mass spectrometric and UV/vis data with a database search, these compounds were attributed to four members of the macrolactin family, macrolactin A and D as well as 7-O-malonyl- and 7-O-succinyl-macrolactin. This conclusion was verified by the isolation and structure elucidation of macrolactin A using mass spectrometric and 2D-NMR studies. Macrolactin biosynthesis was investigated using feeding experiments with (13)C-acetate. (13)C-labelled macrolactin A revealed an alternating labelling of its carbon skeleton with (13)C, indicating that acetate/malonate was used as the sole precursor. The macrolactin structure is compatible with the domain organization of the pks2 operon. Similarly to pks1 and pks3, pks2 is a modular polyketide synthase system of type I which exhibits a trans-acyltransferase architecture using a discrete acyltransferase enzyme iteratively in the assembly of macrolactin. Finally, the potential for macrolactin production on a genetic and metabolic basis was found to be widely distributed among Bacillus amyloliquefaciens strains. PMID- 17845000 TI - Lipoxazolidinones A, B, and C: antibacterial 4-oxazolidinones from a marine actinomycete isolated from a Guam marine sediment. AB - Marine actinomycete strain NPS008920, a member of the new genus Marinispora, was isolated from a sediment sample collected in Cocos Lagoon, Guam. In natural sea water containing media, the strain produced a series of novel 2-alkylidene-5 alkyl-4-oxazolidinones, lipoxazolidinone A (1), B (2), and C (3). Compounds 1- 3 showed broad spectrum antimicrobial activity similar to that of the commercial antibiotic linezolid (Zyvox), a 2-oxazolidinone. Hydrolysis of the amide bond of the 4-oxazolidinone ring of 1 resulted in loss of antibacterial activity. The 2 alkylidene-4-oxazolidinone represents a new antibiotic pharmacophore and is unprecedented in nature. PMID- 17845001 TI - Bioactive constituents of the roots of Polyalthia cerasoides. AB - A new dimeric aporphine alkaloid, bidebiline E (1), and a new natural product, octadeca-9,11,13-triynoic acid (2), along with three known sesquiterpenes, alpha humulene (3), caryophyllene oxide (4), and (-)-alpha-cadinol (5), and four known isoquinoline alkaloids, laudanosine (6), codamine (7), laudanidine (8), and reticuline (9), were isolated from the roots of Polyalthia cerasoides. The structures of compounds 1 and 2 were established on the basis of their 1D and 2D NMR spectroscopic data. Among these isolates, 1, 2, 4, 7, and 8 exhibited antimalarial activity against Plasmodium falciparum, while 1- 3 showed antimycobacterial activity against Mycobacterium tuberculosis using in vitro assays. PMID- 17845002 TI - Sesquiterpenoids and artificial 19-oxygenated steroids from the formosan soft coral Nephthea erecta. AB - Chemical investigations on the acetone and MeOH solubles of the soft coral Nephthea erecta have afforded five new sesquiterpenoids (1-5), one known sesquiterpene, kelsoene (6), and two known 19-oxygenated steroids (10 and 11). In addition, three unexpected artificial 19-oxygenated steroids (7-9) were obtained by letting 10 and 11 stand in CDCl(3) for prolonged periods of time. The structures of 1-9 were elucidated by extensive spectroscopic analyses, and their cytotoxicity against selected cancer cells was measured in vitro. PMID- 17845004 TI - Label-free sensing of binding to microarrays using Brewster angle straddle interferometry. AB - We report an interferometric method to detect chemical binding at an interface. The interference layer consists of the thin native oxide on silicon, and we utilize nearly opposite phase shifts of light at the oxide/water and oxide/silicon interfaces to achieve near-complete destructive interference. We measure selective binding of thrombin in solution to DNA aptamers covalently bound to the oxide. The technique can be used to detect and quantify surface binding of less than 1 A of material, sensitivity similar to that of surface plasmon resonance imaging or arrayed imaging reflectometry. Results are in quantitative agreement with what is predicted theoretically. The method is very convenient to implement since it utilizes unmodified silicon wafers as substrates and is extremely insensitive to both probe light bandwidth and collimation. PMID- 17845005 TI - Fabrication of fritless chromatographic microchips packed with conventional reversed-phase silica particles. AB - This paper describes the development and study of a disposable and inexpensive microfluidic chip, fabricated from poly(dimethylsiloxane) (PDMS) incorporating conventional chromatographic reversed-phase silica particles (C18) without the use of frits, permanent physical barriers, tapers, or restrictors. The packing of C18 modified silica particles into the microfluidic channels is made possible by the hydrophobic nature and excellent elasticity of PDMS. Keystone-, clamping-, and anchor-effects provide the stability and the compactness of the packing and attenuated wall-effects were observed. PMID- 17845003 TI - Conjugated platinum(IV)-peptide complexes for targeting angiogenic tumor vasculature. AB - The integrins alpha vbeta3 and alpha vbeta5 and the membrane-spanning surface protein aminopeptidase N (APN) are highly expressed in tumor-induced angiogenesis, making them attractive targets for therapeutic intervention. Both integrins and APN recognize a broad range of peptides containing RGD (Arg-Gly Asp) and NGR (Asn-Gly-Arg) motifs, respectively. Here, we describe the design, synthesis, and characterization of a series of mono- and difunctionalized platinum(IV) complexes in which a conjugated peptide motif, containing RGD, (CRGDC)c, (RGDfK)c, or NGR, is appended as a "tumor-homing device" to target tumor endothelial cells selectively over healthy cells. Platinum(IV)-peptide complexes with nonspecific amino acids or peptide moieties were prepared as controls. Concentration-response curves of these compounds were evaluated against primary proliferating endothelial cells and tumor cell lines and compared to those of cisplatin, a well-described platinum-based chemotherapeutic agent. The Pt(IV)-RGD conjugates were highly and specifically cytotoxic to cell lines containing alpha vbeta3 and alpha vbeta5, approaching the activity of cisplatin. The Pt(IV)-NGR complexes were less active than Pt(IV)-RGD-containing compounds but more active than nonspecific Pt-peptide controls. Integrin alpha vbeta3 mediated, at least in part, the anti-proliferative effect of a Pt(IV)-RGD conjugate, as demonstrated by a decreased inhibitory response when endothelial cells were either (1) incubated with an excess of alpha vbeta3/alpha vbeta5 specific RGD pentapeptides or (2) transfected with RNAi for beta 3, but not beta 1, integrins. These results suggest a rational approach to improved chemotherapy with Pt(IV)-peptide conjugates by selective drug delivery to the tumor compartment. PMID- 17845006 TI - MS/MS simplification by 355 nm ultraviolet photodissociation of chromophore derivatized peptides in a quadrupole ion trap. AB - Ultraviolet photodissociation (UVPD) of chromophore-modified peptides enhances the capabilities for de novo sequencing in a quadrupole ion trap mass spectrometer. Attachment of UV chromophores allows efficient photoactivation of not only the precursor ions but also any fragments that retain the chromophore functionality. For doubly protonated peptides, UVPD leads to a vast reduction in MS/MS complexity. The array of b and y ions typically seen upon collisionally activated dissociation is reduced to a single series of either y or b ions by UVPD depending on the location of the chromophore (i.e., N- or C-terminus). The sulfonation reagent Alexa Fluor 350 (AF350) provided the best overall results for the singly and doubly charged peptides by UVPD. The nonsulfonated analogue of AF350, 7-amino-4-methylcoumarin-3-acetic acid, also led to simplified spectra for doubly charged, but not singly charged, peptides by UVPD. Dinitrophenyl-peptides also yielded simplified spectra by UVPD albeit with a small amount of internal fragments accompanying the series of diagnostic y ions. The success of this MS/MS simplification process stems from extensive secondary fragmentation of any chromophore-containing fragments upon exposure to subsequent laser pulses. Energy variable UVPD reveals that the abundances of non-chromophore-containing y fragment ions increase linearly with laser pulse energy, suggesting secondary dissociation of these species is insignificant. The abundances of chromophore containing a/b fragment ions follow a quadratic trend due to the extensive secondary fragmentation at higher laser energies or multiple pulses. PMID- 17845007 TI - Phage anti-immune complex assay: general strategy for noncompetitive immunodetection of small molecules. AB - Due to their size, small molecules cannot be simultaneously bound by two antibodies, precluding their detection by noncompetitive two-site immunoassays, which are superior to competitive ones in terms of sensitivity, kinetics, and working range. This has prompted the development of anti-immune complex antibodies, but these are difficult to produce, and often exhibit high cross reactivity with the unliganded primary antibody. This work demonstrates that anti immune complex antibodies can be substituted by phage particles isolated from phage display peptide libraries. Phages bearing specific small peptide loops allowed to focus the recognition to changes in the binding area of the immune complex. The concept was tested using environmental and drug analytes; with improved sensitivity and ready adaptation into on-site formats. Peptides specific for different immune complexes can be isolated from different peptide libraries in a simple and systematic fashion allowing the rapid development of noncompetitive assays for small molecules. PMID- 17845008 TI - Loop202-208 in avian sarcoma virus integrase mediates tetramer assembly and processing activity. AB - Integrase (IN) catalyzes insertion of the retroviral genome into the host via two sequential reactions. The processing activity cleaves the 3'-dinucleotides from the two ends of the viral DNA which are then inserted into the host DNA. Tetramers are required for the joining step. While dimers have been shown to catalyze processing, they do so inefficiently, and the oligomeric requirement for processing is unknown. We have replaced loop202-208 at the putative dimer-dimer interface of the avian sarcoma virus IN with its analogue, loop188-194, from human immunodeficiency virus IN. The mutation abolished disintegration activity and a 2 x 10(-2) s-1 fast phase during single-turnover processing. A 3 x 10(-4) s 1 slow processing phase was unaffected. Preincubation with a DNA substrate known to promote tetramerization increased products formed during the fast phase by 2.5 fold only for wild-type IN, correlating the fast and slow phases with processing by tetramers and dimers, respectively. We propose a novel tetramer model for coupling processing and integration based on efficient processing by the tetramer. We provide for the first time direct evidence of the functional relevance of a structural element, loop202-208, which appears to be required for mediating the interaction between dimer halves of the active tetramer. PMID- 17845010 TI - Low-light-induced formation of semicrystalline photosystem II arrays in higher plant chloroplasts. AB - Remodeling of photosynthetic machinery induced by growing spinach plants under low light intensities reveals an up-regulation of light-harvesting complexes and down-regulation of photosystem II and cytochrome b6f complexes in intact thylakoids and isolated grana membranes. The antenna size of PSII increased by 40 60% as estimated by fluorescence induction and LHCII/PSII stoichiometry. These low-light-induced changes in the protein composition were accompanied by the formation of ordered particle arrays in the exoplasmic fracture face in grana thylakoids detected by freeze-fracture electron microscopy. Most likely these highly ordered arrays consist of PSII complexes. A statistical analysis of the particles in these structures shows that the distance of neighboring complexes in the same row is 18.0 nm, the separation between two rows is 23.7 nm, and the angle between the particle axis and the row is 26 degrees . On the basis of structural information on the photosystem II supercomplex, a model on the supramolecular arrangement was generated predicting that two neighboring complexes share a trimeric light-harvesting complex. It was suggested that the supramolecular reorganization in ordered arrays in low-light grana thylakoids is a strategy to overcome potential diffusion problems in this crowded membrane. Furthermore, the occurrence of a hexagonal phase of the lipid monogalactosyldiacylglycerol in grana membranes of low-light-adapted plants could trigger the rearrangement by changing the lateral membrane pressure. PMID- 17845011 TI - Stability and dynamics of the porcine odorant-binding protein. AB - The denaturation process of porcine odorant-binding protein (pOBP) was studied by intrinsic fluorescence analysis and far- and near-UV circular dichroism measurements. Our results showed that a reversible one-step process described the denaturation by GdnHCl. The midpoint of the transition, that is, the point where the free energies of protein in the native and unfolded states are equal, corresponds to 2.3 M GdnHCl. The difference in free energy between native and unfolded states of pOBP is -5.95 kcal/mol in the absence of GdnHCl, indicating that the protein molecule is very stable to the denaturing action of GdnHCl. A 15% increase in fluorescence intensity accompanied by a 25% decrease of fluorescence decay lifetime recorded in the range of 0.0-1.4 M GdnHCl was explained by the destruction of the complex between Trp 16 and the positively charged atom NZ of Lys 120, localized over the center of the Trp 16 indole ring, with concurrent formation of complex between Trp 16 and bound water molecules also located in its close vicinity. PMID- 17845009 TI - Sequence-specific triple helix formation with genomic DNA. AB - We have previously demonstrated site-specific delivery of antiparallel phosphorothioate triplex forming oligonucleotide (TFO) specific to -165 to -141 promoter region of alpha1(I) collagen (abbreviated as APS165) to hepatic stellate cells (HSCs) of fibrotic rats after conjugation with mannose 6-phosphate-bovine serum albumin. However, we still need to determine whether there is correlation between transcription inhibition and triplex formation with genomic DNA. In this study, APS165 was modified with psoralen and the extent of triplex formation with alpha1(I) collagen DNA was determined in naked genomic DNA, isolated nuclei of HSC-T6 cells and whole cells by using a simple real-time PCR based method. In this method, a purification step was added to remove unbound APS165, which eliminated the possible artifacts during real-time PCR. Psoralen photoadduct formation was shown to be essential to retain triplex structure under denaturing conditions. On naked genomic DNA, 82.2% of DNA formed triplex and 36.7% of genomic DNA in isolated nuclei at 90 min contained triplex structure. As quantified by real-time PCR, 50% of genomic DNA in living cells at 12 h postincubation contained triplex structures. Furthermore, the triplex formation was dose-dependent with 26.5% and 50% of DNA having triplex structure at concentrations of 1 microM and 5 microM, respectively. Moreover, on a plasmid pCol-CAT220 containing rat alpha1(I) gene promoter (-225 to +113), 75.3% of triplex formation was observed, which was correlated with a 73.6% of transcription inhibition. These findings will further strengthen the therapeutic applications of APS165. PMID- 17845012 TI - Discovery of singlet diradicals: theoretical study on the cage species C14N12-H6 and its six derivatives. AB - In this work, the geometries, harmonic vibrational frequencies, and high-energy density material (HEDM) properties of a novel species and its six derivatives with the general formula C14N12-R6 (R = H, OH, F, CN, N3, NH2, and NO2) have been investigated at the restricted and unrestricted B3LYP/cc-pVDZ levels of theory. Natural bond orbital (NBO), natural orbital (NO), and atoms in molecules (AIM) analyses are applied to examine their electronic topologies. It is found that for the four species of R = H, CN, N3, and NO2, (1) there exist high LUMO occupation numbers, (2) there is considerable spin density congregated on the two central carbon atoms, (3) there exists through space interaction (or intramolecular interaction, which is one of the stabilizing factors of a diradicaloid) between the two central carbon atoms, (4) the distance (about 3 A) between the two central carbon atoms (as the apexes of two trigonal pyramids with their bases facing each other) is suitable and favorable for diradical formation. All the results support that these four species are diradicals or diradicaloids. Furthermore, the appreciable singlet-triplet energy gaps indicate that these four diradicals tend to have a singlet ground state. There is a moderate HOMO-LUMO gap (on the order of 1.5 to 2.1 eV) for these four species. These four singlet diradicals may be novel organic semiconductor materials or nonlinear optical materials. On the other hand, the remaining three species, with R = OH, F, and NH2, are not diradicaloids. PMID- 17845013 TI - Mixed-valence polyoxometalates: spin-coupling and electron distribution in the decawolframate anion reduced by two electrons. AB - The decawolframate anion reduced by two electrons, W10O326-, is diamagnetic, and its two "extra" electrons delocalize mainly among its eight equatorial wolfram sites. In this work, we combine a phenomenological Hamiltonian with first principles calculations to explain the origin of these properties. Through ab initio calculations and effective Hamiltonians on fragments, we determine the values of the magnetic exchange parameters, J, the transfer integrals, t, the Coulombic repulsions, V, and the orbital energies, epsilon. Then, by introducing these parameters in a model Hamiltonian simulating the whole molecule, one obtains that the singlet-triplet gap is 780 meV and that more than a 90% of the "extra" electron density resides on the eight equatorial wolfram ions. An analysis of the interplay between these parameters indicates that electron transfer processes play a dominant role while magnetic exchange has only a minor influence. PMID- 17845015 TI - Microcanonical transition state theory for activated gas-surface reaction dynamics: application to H2/CU(111) with rotation as a spectator. AB - A microcanonical unimolecular rate theory (MURT) model incorporating quantized surface vibrations and Rice-Ramsperger-Kassel-Marcus rate constants is applied to a benchmark system for gas-surface reaction dynamics, the activated dissociative chemisorption and associative desorption of hydrogen on Cu(111). Both molecular translation parallel to the surface and rotation are treated as spectator degrees of freedom. MURT analysis of diverse experiments indicates that one surface oscillator participates in the dissociative transition state and that the threshold energy for H2 dissociation on Cu(111) is E0 = 62 kJ/mol. The spectator approximation for rotation holds well at thermally accessible rotational energies (i.e., for Er less than approximately 40 kJ/mol). Over the temperature range from 300 to 1000 K, the calculated thermal dissociative sticking coefficient is ST = S0 exp(-Ea/kBT) where S0 = 1.57 and Ea = 62.9 kJ/mol. The sigmoid shape of rovibrational eigenstate-resolved dissociative sticking coefficients as a function of normal translational energy is shown to derive from an averaging of the microcanonical sticking coefficient, with threshold energy E0, over the thermal surface oscillator distribution of the gas-surface collision complexes. Given that H2/Cu(111) is one of the most dynamically biased of gas-surface reactive systems, the simple statistical MURT model simulates and broadly rationalizes the H2/Cu(111) reactive behavior with remarkable fidelity. PMID- 17845016 TI - How to model solvent effects on molecular properties using quantum chemistry? Insights from polarizable discrete or continuum solvation models. AB - We present a comparative study of solvent effects on the 15N NMR shielding constants and the lowest electronic excitation energy (n --> pi*) in the three diazines (pyrazine, pyrimidine, and pyridazine) in aqueous solution. This solvent is modeled using either a polarizable continuum model (PCM) or a discrete polarizable model (DPM). We analyze the results obtained with the two models in terms of differences/similarities in the reaction field produced at the solute. The PCM reaction field is found to be quite sensitive to the dimension of the cavity and so are the molecular properties. However, constructing the cavity so that the DPM and PCM reaction fields become similar in magnitude leads to quite similar results for the studied molecular properties modeling the solvent using either the PCM or the DPM. Compared to experimental data, the most accurate predicted results are obtained by describing the closest water molecules at the same level of sophistication as that of the solute, whereas the bulk solvent may be described using either PCM or MM. Finally, a comparison with geometry optimized clusters seems to show that it is important to check potential deficiencies in the force field in order for this to treat hydrogen bonding in a consistent manner. PMID- 17845014 TI - Rate constants of hydroperoxyl radical addition to cyclic nitrones: a DFT study. AB - Nitrones are potential synthetic antioxidants against the reduction of radical mediated oxidative damage in cells and as analytical reagents for the identification of HO2* and other such transient species. In this work, the PCM/B3LYP/6-31+G(d,p)//B3LYP/6-31G(d) and PCM/mPW1K/6-31+G(d,p) density functional theory (DFT) methods were employed to predict the reactivity of HO2* with various functionalized nitrones as spin traps. The calculated second-order rate constants and free energies of reaction at both levels of theory were in the range of 100-103 M-1 s-1 and 1 to -12 kcal mol-1, respectively, and the rate constants for some nitrones are on the same order of magnitude as those observed experimentally. The trend in HO2* reactivity to nitrones could not be explained solely on the basis of the relationship of the theoretical positive charge densities on the nitronyl-C, with their respective ionization potentials, electron affinities, rate constants, or free energies of reaction. However, various modes of intramolecular H-bonding interaction were observed at the transition state (TS) structures of HO2* addition to nitrones. The presence of intramolecular H-bonding interactions in the transition states were predicted and may play a significant role toward a facile addition of HO2* to nitrones. In general, HO2* addition to ethoxycarbonyl- and spirolactam-substituted nitrones, as well as those nitrones without electron-withdrawing substituents, such as 5,5 dimethyl-pyrroline N-oxide (DMPO) and 5-spirocyclopentyl-pyrroline N-oxide (CPPO), are most preferred compared to the methylcarbamoyl-substituted nitrones. This study suggests that the use of specific spin traps for efficient trapping of HO2* could pave the way toward improved radical detection and antioxidant protection. PMID- 17845017 TI - Polyfluorinated bis-styrylbenzene beta-amyloid plaque binding ligands. AB - beta-Amyloid (Abeta) binding affinities and specificities for six bis styrylbenzenes with multiple magnetically equivalent fluorine atoms in the form of a tetrafluorophenyl core or symmetrical trifluoromethyl and trifluoromethoxy groups were determined by means of fluorescence titrations with amyloid peptide Abeta1-40 and a novel in vitro fluorescence-based assay using APP/PS1 transgenic mouse brain sections. Bis-styrylbenzenes with a tetrafluorophenyl core had increased Abeta binding affinities compared to their monofluorophenyl or phenyl counterparts. Bis-styrylbenzenes with carboxylic acid functional groups had lower Abeta binding affinities than their neutral counterparts. Selected bis styrylbenzenes were demonstrated to have good blood-brain barrier penetration capabilities. These data extend the SAR of bis-styrylbenzene Abeta binding and provide direction for the development of a noninvasive probe for early detection of Alzheimer's disease using 19F MRI. PMID- 17845018 TI - Enzyme adaptation to inhibitor binding: a cryptic binding site in phenylethanolamine N-methyltransferase. AB - Shape complementarity is a fundamental principle of inhibitor design. Here we show that an enzyme for which the crystal structure has been determined (phenylethanolamine N-methyltransferase, PNMT) conceals a cryptic binding site. This site is revealed upon binding of inhibitors that are double the size of the physiological substrate. These large inhibitors are not predicted to bind in that they protrude through the accessible surface calculated from a PNMT/7 aminosulfonyl-1,2,3,4-tetrahydroisoquinoline (SK&F 29661) crystal structure, yet they are potent inhibitors of PNMT. We determined structures of the enzyme complexed with large inhibitors and found that the volume of the active site increases by 140 A3 upon binding. Changes in active site size and shape are brought about by unfavorable side chain conformations and rigid body helix motions. The energetic cost is modest, estimated at 2-3 kcal/mol from mutational analyses. Our findings further underline the importance of protein flexibility in structure-based inhibitor design studies. PMID- 17845019 TI - Pyrido[1,2-a]pyrimidin-4-one derivatives as a novel class of selective aldose reductase inhibitors exhibiting antioxidant activity. AB - 2-Phenyl-pyrido[1,2-a]pyrimidin-4-one derivatives bearing a phenol or a catechol moiety in position 2 were tested as aldose reductase (ALR2) inhibitors and exhibited activity levels in the micromolar/submicromolar range. Introduction of a hydroxy group in position 6 or 9 gave an enhancement of the inhibitory potency (compare 18, 19, 28, and 29 vs 13 and 14). Lengthening of the 2-side chain to benzyl determined a general reduction in activity. The lack or the methylation of the phenol or catechol hydroxyls gave inactive (10-12, 21, 22, 25-27) or scarcely active (15, 17, 20) compounds, thus demonstrating that the phenol or catechol hydroxyls are involved in the enzyme pharmacophoric recognition. Moreover, all the pyridopyrimidinones displayed significant antioxidant properties, with the best activity shown by the catechol derivatives. The theoretical binding mode of the most active compounds obtained by docking simulations into the ALR2 crystal structure was fully consistent with the structure-activity relationships in the pyrido[1,2-a]pyrimidin-4-one series. PMID- 17845020 TI - Nitric oxide donor beta2-agonists: furoxan derivatives containing the fenoterol moiety and related furazans. AB - The structure of fenoterol, a beta2-adrenoceptor agonist used in therapy, has been joined with furoxan NO-donor moieties to give new NO-donor beta2-agonists. The furazan analogues, devoid of the property to release NO, were also synthesized for comparison. All the compounds retained beta2-agonistic activity at micromolar or submicromolar concentration when tested on guinea pig tracheal rings precontracted with carbachol. Among the furoxan derivatives, the NO contribution to trachea relaxation was evident with product 15b at micromolar concentrations. All the new NO-donor hybrids were able to dilate rat aortic strips precontracted with phenylephrine. Both furoxan and furazan derivatives displayed antioxidant activity greater than that of fenoterol. PMID- 17845021 TI - Proteome of murine jejunal brush border membrane vesicles. AB - The first detailed description of the proteome of the mouse jejunal brush border membrane vesicle is presented here. This was obtained by a combination of purification via divalent (Mg2+) cation precipitation starting with isolated cells plus strong cation exchange chromatography LC-MS/MS. Five-hundred seventy proteins were identified including 45 transport proteins. Among the latter, 18 had either not been identified in the intestine in the past or there was a single unconfirmed report of their presence. Validation was accomplished by a combination of immunoblotting and immunofluorescence using mouse jejunum and previously described antibodies. The validated BB proteins were aquaporin 7, Glut 9b, Na+I- symporter (NIS), and non-gastric H+/K+-ATPase. This study helps to further define the brush border membrane vesicle, a preparation which has been widely used to identify transport function of the small intestine. PMID- 17845022 TI - Extra virgin olive oils increase hepatic fat accumulation and hepatic antioxidant protein levels in APOE-/- mice. AB - We assessed the effects of Picual and Arbequina olive oil, rich and poor in polyphenols, respectively, on plasma lipid and glucose metabolism, hepatic fat content, and the hepatic proteome in female Apoe-/- mice. Both olive oils increased hepatic fat content and adipophilin levels (p < 0.05), though Picual olive oil significantly decreased plasma triglycerides (p < 0.05). Proteomics identified a range of hepatic antioxidant enzymes that were differentially regulated by both olive oils as compared with palm oil. We found a clear association between olive oil consumption and differential regulation of adipophilin and betaine homocysteine methyl transferase as modulators of hepatic triglyceride metabolism. Therefore, our "systems biology" approach revealed hitherto unrecognized insights into the triglyceride-lowering and anti atherogenic mechanisms of extra virgin olive oils, wherein the up-regulation of a large array of anti-oxidant enzymes may offer sufficient protection against lesion development and diminish oxidative stress levels instigated by hepatic steatosis. PMID- 17845024 TI - Thermodynamic properties of methane hydrate in quartz powder. AB - Using the experimental method of precision adiabatic calorimetry, the thermodynamic (equilibrium) properties of methane hydrate in quartz sand with a grain size of 90-100 microm have been studied in the temperature range of 260-290 K and at pressures up to 10 MPa. The equilibrium curves for the water-methane hydrate-gas and ice-methane hydrate-gas transitions, hydration number, latent heat of hydrate decomposition along the equilibrium three-phase curves, and the specific heat capacity of the hydrate have been obtained. It has been experimentally shown that the equilibrium three-phase curves of the methane hydrate in porous media are shifted to the lower temperature and high pressure with respect to the equilibrium curves of the bulk hydrate. In these experiments, we have found that the specific heat capacity of the hydrate, within the accuracy of our measurements, coincides with the heat capacity of ice. The latent heat of the hydrate dissociation for the ice-hydrate-gas transition is equal to 143 +/- 10 J/g, whereas, for the transition from hydrate to water and gas, the latent heat is 415 +/- 15 J/g. The hydration number has been evaluated in the different hydrate conditions and has been found to be equal to n = 6.16 +/- 0.06. In addition, the influence of the water saturation of the porous media and its distribution over the porous space on the measured parameters has been experimentally studied. PMID- 17845023 TI - Daunomycin binding to detergent micelles: a model system for evaluating the hydrophobic contribution to drug-DNA interactions. AB - The interaction of daunomycin with sodium dodecyl sulfate and Triton X-100 micelles was investigated as a model for the hydrophobic contribution to the free energy of DNA intercalation reactions. Measurements of visible absorbance, fluorescence lifetime, steady-state fluorescence emission intensity, and fluorescence anisotropy indicate that the anthraquinone ring partitions into the hydrophobic micelle interior. Fluorescence quenching experiments using both steady-state and lifetime measurements demonstrate reduced accessibility of daunomycin in sodium dodecyl sulfate micelles to the anionic quencher iodide and to the neutral quencher acrylamide. Quenching of daunomycin fluorescence by iodide in Triton X-100 micelles was similar to that seen with free daunomycin. Studies of the energetics of the interaction of daunomycin with micelles by fluorescence and absorbance titration methods and by isothermal titration calorimetry in the presence of excess micelles revealed that association with sodium dodecyl sulfate and Triton X-100 micelles is driven by a large negative enthalpy. Association of the drug with both types of micelles also has a favorable entropic contribution, which is larger in magnitude for Triton X-100 micelles than for sodium dodecyl sulfate micelles. The thermodynamic profile for the interaction of daunomycin with both types of micelles is characteristic of the "nonclassical" hydrophobic effect. The enthalpy for the interaction of daunomycin with sodium dodecyl sulfate micelles increases nonlinearly with temperature, indicating a positive (and temperature dependent) heat capacity change. The binding isotherm for daunomycin association with sodium dodecyl sulfate micelles was cooperative, with a Hill coefficient of 1.6. The cooperative behavior and the positive heat capacity change suggest that the drug alters micelle size or imposes order on the hydrocarbon interior of the micelle. PMID- 17845026 TI - Chiral discrimination of a gemini-type surfactant with rigid spacer at the air water interface. AB - Spontaneous separation of chiral phases was observed in the monolayers of a racemate of gemini-type twin-tailed, twin-chiral amphiphiles, (2R,3R)-(+) bis(decyloxy)succinic acid and (2S,3S)-(-)-bis(decyloxy)succinic acid. The pressure-area isotherms of the interfacial monolayers formed at the liquid-air interface, and the 2D lattice structures studied through surface probe measurements revealed that the racemate exhibits a homochiral discrimination of the enantiomers in two dimensions. An enantiomeric excess (e,e) of 20% was sufficient to break the chiral symmetry at the air-water interface for a homochiral interaction. Langmuir monolayers on ZnCl2 and CaCl2 subphases manifested chiral discrimination with Zn2+ evidencing homochiral interaction with a chelate-type complex, whereas Ca2+ resulted in a heterochiral interaction forming an ionic-type complex. For the chiral asymmetric units, oblique and rectangular unit cells of the racemic monolayer had exclusive requirements of homo- and heterochiral recognitions for Zn2+ and Ca2+ ions, respectively. Monolayers transferred from the condensed phase at 25 mN/m onto hydrophilic Si(100) and quartz substrates revealed the formation of bilayers through transfer induced monolayer buckling. The emergence of homochiral discrimination was explained using the effective-pair-potential (EPP) approach. PMID- 17845025 TI - Relative ground and excited-state pKa values of phytochromobilin in the photoactivation of phytochrome: a computational study. AB - The conversion of the plant photoreceptor phytochrome from an inactive (Pr) to an active form (Pfr) is accomplished by a red-light induced Z --> E photoisomerization of its phytochromobilin chromophore. In recent years, the question whether the photoactivation involves a change in chromophore protonation state has been the subject of many experimental studies. Here, we have used quantum chemical methods to calculate relative ground and excited-state pKa values of the different pyrrole moieties of phytochromobilin in a protein-like environment. Assuming (based on experimental data) a Pr ZaZsZa chromophore and considering isomerizations at C15 and C5, it is found that moieties B and C are the strongest acids both in the ground state and in the bright first singlet excited state, which is rationalized in simple geometric and electronic terms. It is also shown that neither light absorption nor isomerization increases the acidity of phytochromobilin relative to the reference Pr state with all pyrrolenic nitrogens protonated. Hence, provided that the subset of chromophore geometries under investigation is biologically relevant, there appears to be no intrinsic driving force for a proton-transfer event. In a series of benchmark calculations, the performance of ab initio and time-dependent density functional theory methods for excited-state studies of phytochromobilin is evaluated in light of available experimental data. PMID- 17845027 TI - Preparation, photophysics, and electrochemistry of segmented comonomers consisting of thiophene and pyrimidine units: new monomers for hybrid copolymers. AB - An efficient coupling route to novel pi-conjugated comonomers consisting of pyrimidine, thiophene, and bithiophene units was developed. The novel pi-donor acceptor-donor and pi-donor-acceptor-acceptor-donor conjugated compounds were prepared by Suzuki heterocoupling and Ni(0)-mediated Ullman homocoupling reactions. Photophysical investigation of these alternating pi-donor and acceptor compounds indicated that the deactivation of their singlet excited state proceeds predominately by fluorescence and results in high fluorescence quantum yields. Intersystem crossing to the triplet state was also present in ca. 10%. Quantification of the triplet manifold by laser flash photolysis further revealed that bithiophene produced its triplet state in only 31%. Cyclic voltammetry studies showed that the comonomers undergo both oxidation and reduction leading to their radical cations and radical anions, respectively. The radical cations are highly reactive and undergo anodic polymerization resulting in mutual p- and n-type dopable polymers. The extended conjugation resulting from polymer formation was confirmed by both absorbance and fluorescence spectroscopy and by GPC. Ruthenium binding with the conjugated homocoupled ligand was also found resulting in a hybrid alternating copolymer with significantly different spectroscopic and electrochemical properties relative to its metal-free counterpart. PMID- 17845028 TI - Hydrogen bonding and multiphonon structure in copper pyrazine coordination polymers. AB - We report a systematic investigation of the temperature-dependent infrared vibrational spectra of a family of chemically related coordination polymer magnets based upon bridging bifluoride (HF(2)-) and terminal fluoride (F-) ligands in copper pyrazine complexes including Cu(HF(2))(pyz)(2)BF(4), Cu(HF(2))(pyz)(2)ClO(4), and CuF(2)(H(2)O)(2)(pyz). We compare our results with several one- and two-dimensional prototype materials including Cu(pyz)(NO(3))(2) and Cu(pyz)(2)(ClO(4))(2). Unusual low-temperature hydrogen bonding, local structural transitions associated with stronger low-temperature hydrogen bonding, and striking multiphonon effects that derive from coupling of an infrared-active fundamental with strong Raman-active modes of the pyrazine building-block molecule are observed. On the basis of the spectroscopic evidence, these interactions are ubiquitous to this family of coordination polymers and may work to stabilize long-range magnetic ordering at low temperature. Similar interactions are likely to be present in other molecule-based magnets. PMID- 17845029 TI - Sandwich compounds of cyanotrispyrazolylborates: complexation-induced ligand isomerization. AB - Reaction of the new cyanoscorpionate ligand, hydrotris(4-cyano-3 phenyl)pyrazolylborate (Tp(Ph),(4CN)) with Co(II), Mn(II), and Fe(II) unexpectedly results in the isolation only of crystals containing sandwich complexes in which the ligands have been isomerized to produce the heterocyanoscorpionate hydrobis(4-cyano-3-phenylpyrazolyl)(4-cyano-5 phenylpyrazolyl)borate (Tp(Ph),(4CN*)). The three complexes have been characterized crystallographically and are isostructural, with each ligand acting in a tridentate manner toward the metal. The isomerization of the ligand appears to be more facile than that of the analogous non-cyano ligand, Tp(Ph), with which crystals of the unisomerized sandwich compound have been isolated for Mn(II) and Fe(II). PMID- 17845030 TI - Tuning of magnetic properties of polynuclear lanthanide(III) octacyanotungstate(V) systems: determination of ligand-field parameters and exchange interaction. AB - The self-assembly reaction between trivalent lanthanide ions, 2,2':6',2' ' terpyridine (terpy) ligand, and octacyanotungstate(V) leads to the formation of two series of isomorphous cyano-bridged compounds: (i) one-dimensional (1-D) chains [Ln(terpy)(DMF)(4)][W(CN)(8)].6H(2)O.C(2)H(5)OH (Ln = Ce-Dy) and (ii) dinuclear molecules [Ln(terpy)(DMF)(2)(H(2)O)(2)][W(CN)(8)].3H(2)O (Ln = Ho, Er, Yb) and the ionic [Tm(III)(terpy)(DMF)(2)(H(2)O)(3)][WV(CN)(8)].4H(2)O.DMF (DMF = N,N-dimethylformamide) system. The crystal structures of 1-D chains consist of alternating {[W(CN)(8)]} and {[Ln(terpy)]} building blocks. The neighboring chains are weakly linked through the pi-pi stacking interactions of the aromatic rings, leading to two-dimensional supramolecular layers. The dinuclear species are weakly linked through the hydrogen bonds between H2O molecules and terminal cyano ligands resulting in a columnlike arrangement of dimers. Taking into account the ligand-field splitting and the exchange interaction, we have estimated the magnetic couplings between the Ln(III) and WV centers in a series of polycrystalline 1-D chains and in dimeric systems. The corresponding exchange constants have been shown to change the sign along the series of chains. The coupling is antiferromagnetic for 1 (J = -0.24 cm(-1)) and 2 (J = -0.07 cm(-1)), whereas 3 (J = +0.47 cm(-1)), 7 (J = +0.28 cm(-1)), and 8 (J = +0.23 cm(-1)) have ferromagnetic character. In the case of dimeric systems, the coupling constants seem to be independent of the lanthanide center. The splitting structures of the ground-state multiplets of the Ln(III) centers have been shown to explain the temperature dependences of the magnetic susceptibilities. PMID- 17845031 TI - Effect of strain in the proximal ligand on the binding of nitric oxide and carbon monoxide to chelated protoheme complexes. AB - The binding of NO and CO to chelated protoheme-l-histidine methyl ester (HM-H), protoheme-glycyl-l-histidine methyl ester (HM-GH), and free protoheme (HM) has been studied in methanol-DMSO solution. In all cases, the NO adducts are five coordinated, indicating that binding of NO occurs with displacement of the axial base, and confirms the strong negative trans effect exerted by NO in heme complexes, though it is found that the presence of strain in the iron-histidine bond of HM-H has a positive influence on NO binding, making it thermodynamically more favorable than for HM-GH. The equilibrium constants thus decrease in the series: HM > HM-H > HM-GH. In contrast to NO, CO has a positive trans effect, and therefore, an opposite trend is observed in the binding of this ligand to the heme complexes. PMID- 17845032 TI - A series of new copper iodobismuthates: structural relationships, optical band gaps affected by dimensionality, and distinct thermal stabilities. AB - Three new copper iodobismuthates, red tetranuclear [n Bu(4)N][Cu(2)(CH(3)CN)(2)Bi(2)I(10)] (1), dark-red infinite linear [Et(4)N](2n)[Cu(2)Bi(2)I(10)](n) (2), and black polymeric ladderlike [Cu(CH(3)CN)(4)](2n)[Cu(2)Bi(2)I(10)](n) (3), crystallize from solutions of BiI3 and CuI in the presence of different cations. A regular structural relationship from 0-D (1) to 1-D linear anion chains (2) to 1-D ladderlike anion chains (3) is observed. The self-assembly of the basic building unit Cu(2)Bi(2)I(10) as altered by different cations is proposed to be the driving force for their formation. The optical band gaps exhibit a structure-related decrease from 1 to 2/3, in agreement with their color changes and the density functional theory (DFT) calculation results. The electronic structures and the relationship with corresponding monobismuth analogues and the Ag-Bi isotypes are discussed on the basis of DFT calculations. In spite of their structural similarities, the compounds are distinctive thermally: 2 is stable to 230 degrees C, 1 undergoes a solvent loss at 85 degrees C to form a new phase that is thermally stable to 230 degrees C, and 3 releases a solvent molecule and decomposes at 80 degrees C into BiI(3) and CuI. The essential reasons for these differences are discussed. PMID- 17845033 TI - One-dimensional array of two- and three-center cation-cation bonds in the structure of Li4[(UO2)10O10(Mo2O8)]. AB - Dark-red crystals of the new compound Li(4)[(UO(2))(10)O10(Mo(2)O(8))] (1) have been obtained by high-temperature solid-state reactions. The structure of 1 (monoclinic, P2(1)/c, a = 7.9426(4) A, b = 19.9895(9) A, c = 10.0796(5) A, beta = 90.575(2) degrees, V = 1600.24(13) A(3), Z = 4) consists of a framework of U and Mo polyhedra with Li+ cations in the channels. The framework contains seven polyhedra-wide uranium oxide tapes interlinked by dimers of edge-sharing [4 + 1] distorted MoO(5) polyhedra. The U-O tapes are parallel to the a axis, and their planes are oriented parallel to (021) and (02) so that they are cross-linked within the framework. The core of the tapes consists of unprecedented one dimensional arrays of cation-cation-bonded uranyl ions. The arrays are constructed from eight-membered cycles with uranyl ions linked through two- and three-center cation-cation interactions. PMID- 17845034 TI - Spectroscopic and computational studies of a Ru(II) terpyridine complex: the importance of weak intermolecular forces to photophysical properties. AB - The complex [Ru(tpy)(CO)(2)TFA]+[PF(6)]- (where tpy = 2,2':6',2' '-terpyridine and TFA = CF(3)CO(2)-) (1) has been synthesized and fully characterized spectroscopically. The X-ray structure of the complex has been determined. The photopysical properties of the ruthenium complex and the free ligand tpy have been investigated at room temperature and at 77 K in acetonitrile solution and in the solid state. Their electronic spectra are highly influenced by intermolecular stacking interactions, both in solution and in the solid state. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations have been performed to characterize the electronic structure and the excited states of [Ru(tpy)(CO)(2)TFA]+[PF(6)]- and tpy. TDDFT calculations on three different conformations of free ligand have been performed as well. Absorption and emission spectra of tpy have been studied at different temperatures and concentrations in order to have a better understanding of this ruthenium derivative's properties. The absorption spectrum of 1 is characterized by metal-perturbed ligand-centered (LC) bands in the UV region. No metal-to-ligand charge transfer (MLCT) bands are observed in the visible for the complex. Only at high concentrations (10(-4) M) does a very weak band appear at 470 nm. At 77 K and low concentrations, solutions of 1 exhibit a major 3LC emission band centered at 468 nm (21.4 x 10(-3) cm(-1)). When the concentration of the complex is increased, an unstructured narrow emission at 603 nm (16.6 x 10(-3) cm(-1)), with a lifetime of 10 micros, dominates the emission spectrum in glassy acetonitrile. This emission originates from a pi-pi stacked dimeric (or oligomeric) species. TDDFT calculations performed on a tail-to-tail dimer structure, similar to that seen in the solid state, ascribe the transition to a triplet excited state, where intermolecular metal (d) --> ligand (pi*, polypyridine) charge transfer occurs. A good estimate of the transition energy is also obtained (623 nm, 1.94 eV). PMID- 17845035 TI - Novel bis(ethylenedithio)tetrathiafulvalene-based organic conductor with 1,1' ferrocenedisulfonate. AB - A new bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF)-based salt with a ferrocenyl moiety, alpha' ''-(BEDT-TTF)(4)(Fe(C(5)H(4)SO(3))(2)).6H(2)O, has been prepared. The ferrocenyl part of this salt is neutral and diamagnetic, but the magnetic susceptibility is well modeled by a Curie-Weiss law with C = 0.142 emu.K.mol(-1) (approximately 1/3 of s = 1/2 spin). The spin is likely to be localized on the donor layer because of its unique charge disproportionation. PMID- 17845036 TI - Facile one-step synthesis of highly ordered bimodal mesoporous phosphosilicate monoliths. PMID- 17845037 TI - The met axial ligand determines the redox potential in Cu(A) sites. PMID- 17845038 TI - Design of emission ratiometric metal-ion sensors with enhanced two-photon cross section and brightness. PMID- 17845039 TI - Catalytic "active-metal" template synthesis of [2]rotaxanes, [3]rotaxanes, and molecular shuttles, and some observations on the mechanism of the cu(i)-catalyzed azide-alkyne 1,3-cycloaddition. AB - A synthetic approach to rotaxane architectures is described in which metal atoms catalyze covalent bond formation while simultaneously acting as the template for the assembly of the mechanically interlocked structure. This "active-metal" template strategy is exemplified using the Huisgen-Meldal-Fokin Cu(I)-catalyzed 1,3-cycloaddition of azides with terminal alkynes (the CuAAC "click" reaction). Coordination of Cu(I) to an endotopic pyridine-containing macrocycle allows the alkyne and azide to bind to metal atoms in such a way that the metal-mediated bond-forming reaction takes place through the cavity of the macrocycle--or macrocycles--forming a rotaxane. A variety of mono- and bidentate macrocyclic ligands are demonstrated to form [2]rotaxanes in this way, and by adding pyridine, the metal can turn over during the reaction, giving a catalytic active metal template assembly process. Both the stoichiometric and catalytic versions of the reaction were also used to synthesize more complex two-station molecular shuttles. The dynamics of the translocation of the macrocycle by ligand exchange in these two-station shuttles could be controlled by coordination to different metal ions (rapid shuttling is observed with Cu(I), slow shuttling with Pd(II)). Under active-metal template reaction conditions that feature a high macrocycle:copper ratio, [3]rotaxanes (two macrocycles on a thread containing a single triazole ring) are also produced during the reaction. The latter observation shows that under these conditions the mechanism of the Cu(I) catalyzed terminal alkyne-azide cycloaddition involves a reactive intermediate that features at least two metal ions. PMID- 17845040 TI - Cobalt-catalyzed reductive coupling of activated alkenes with alkynes. AB - Cobalt complex/Zn systems effectively catalyze the reductive coupling of activated alkenes with alkynes in the presence of water to give substituted alkenes with very high regio- and stereoselectivity in excellent yields. While the intermolecular reaction of acrylates, acrylonitriles, and vinyl sulfones with alkynes takes place in the presence of CoI2(PPh3)2/Zn, the reaction of enones and enals with alkynes requires the use of the CoI2(dppe)/Zn/ZnI2 system. The intramolecular reductive coupling of activated alkenes (enones, enals, acrylates, and acrylonitriles) with alkynes also works efficiently. Further a variety of cyclic lactones and lactams were prepared using this methodology. Possible mechanistic pathways are proposed based on a deuterium-labeling experiment carried out in the presence of D2O. PMID- 17845041 TI - Insights in the organization of DNA-surfactant monolayers using cryo-electron tomography. PMID- 17845042 TI - Macrocyclic and helical oligoamides as a new class of G-quadruplex ligands. PMID- 17845043 TI - Ammonium boranes for the selective complexation of cyanide or fluoride ions in water. AB - With the recognition of aqueous fluoride and cyanide ions as an objective, we have investigated the anion binding properties of two isomeric ammonium boranes, namely [p-(Mes2B)C6H4(NMe3)]+ ([1]+) and [o-(Mes2B)C6H4(NMe3)]+ ([2]+). These cationic boranes, which could be obtained by reaction of the known 4- and 2 dimesitylboryl-N,N-dimethylaniline with MeOTf, have been investigated both experimentally and computationally. They both react with fluoride and cyanide ions in organic solvents to afford the corresponding fluoroborate/ or cyanoborate/ammonium zwitterions 1F, 1CN, 2F, and 2CN. In aqueous solution, however, these cationic boranes behave as remarkably selective receptors. Indeed, [1]+ only complexes cyanide ions while [2]+ only complexes fluoride ions. In H2O/DMSO 60:40 vol (HEPES 6 mM, pH 7), the cyanide binding constant of [1]+ and the fluoride binding constant of [2]+ are respectively equal to 3.9 (+/-0.1) x 108 and 910 (+/-50) M-1. Structural and computational studies indicate that both steric and electronic effects contribute to the unusual selectivity displayed by these cationic boranes. Owing to favorable Coulombic effects, the para-derivative [1]+ has a very high affinity for cyanide; yet these effects are not sufficiently intense to allow complexation of the more efficiently hydrated and less basic fluoride anion. In the case of the ortho-derivative [2]+, the proximity of the ammonium moiety leads to an increase in the Lewis acidity of the boron center thus making fluoride binding possible. However, steric effects prevent cyanide coordination to the boron center of [2]+. Finally, cation [1]+ and [2]+ bind their dedicated anions reversibly and show a negligible response in the presence of other common anions including Cl-, Br-, I-, NO3-, OAc-, H2PO4-, and HSO4-. PMID- 17845044 TI - Synthesis and structures of heteroleptic silylenes. AB - The reaction of benzamidinato silicon trichloride [{PhC(NR)2}SiCl3] [R = Bu(t) (1), SiMe3 (2)] with 2 equiv of potassium in THF afforded mononuclear chlorosilylene [{PhC(NBu(t))2}SiCl] (3) and [{PhC(NSiMe3)2}2SiCl2] (4), respectively. Compound 4 was formed by the disproportionation of unstable [{PhC(NSiMe3)2}SiCl]. The reaction of [{PhC(NBu(t))2}SiCl3] (1) with 1 equiv of LiR (R = NMe2, OBu(t), OPr(i), PPr(i)2) in THF yielded [{PhC(NBu(t))2}SiCl2R] [R = NMe2 (5), OBu(t) (6), OPr(i) (7), PPr(i)2 (8)]. Treatment of 5-8 with 2 equiv of potassium in THF resulted in the novel heteroleptic silylene [{PhC(NBu(t))2}SiR] [R = NMe2 (9), OBu(t) (10), OPr(i) (11), PPr(i)2 (12)]. Compounds 4, 9, and 12 have been analyzed by X-ray crystallography. PMID- 17845045 TI - Independent switching of cubic nonlinear optical properties in a ruthenium alkynyl cruciform complex by employing protic and electrochemical stimuli(1). PMID- 17845046 TI - Charge dependence of a nanoscale supercrystal phase in a supported lipid bilayer. PMID- 17845047 TI - Catalytic and highly regioselective cross-coupling of aromatic C-H substrates. PMID- 17845048 TI - Metal-semiconductor hybrid nanostructure Ag-Zn(0.9)Co(0.1)O: synthesis and room temperature ferromagnetism. PMID- 17845049 TI - Hosting fullerenes by dynamic bond formation with an iridium porphyrin cyclic dimer: a "chemical friction" for rotary guest motions. PMID- 17845050 TI - Chemoenzymatic synthesis of size-defined polysaccharides by sialyltransferase catalyzed block transfer of oligosaccharides. PMID- 17845051 TI - Hyperdimensional protein NMR spectroscopy in peptide-sequence space. PMID- 17845052 TI - Electronic effects in the pt-catalyzed cycloisomerization of propargylic esters: synthesis of 2,3-disubstituted indolizines as a mechanistic probe. AB - The initial 5-exo versus 6-endo cyclization of the acyl group onto the activated alkyne of propargylic esters has been found to be dependent on electronic effects of the acyl, alkyne, and propargylic carbon substituents. These electronic effects control the ratio of 2,3-disubstituted versus 1,3-disubstituted indolizine products formed when substrates bearing pyridines at the alkyne terminus are used. PMID- 17845053 TI - Electroactive oligoaniline-containing self-assembled monolayers for tissue engineering applications. AB - A novel electroactive silsesquioxane precursor, N-(4-aminophenyl)-N'-(4'-(3 triethoxysilyl-propyl-ureido) phenyl-1,4-quinonenediimine) (ATQD), was successfully synthesized from the emeraldine form of amino-capped aniline trimers via a one-step coupling reaction and subsequent purification by column chromatography. The physicochemical properties of ATQD were characterized using mass spectrometry as well as by nuclear magnetic resonance and UV-vis spectroscopy. Analysis by cyclic voltammetry confirmed that the intrinsic electroactivity of ATQD was maintained upon protonic acid doping, exhibiting two distinct reversible oxidative states, similar to polyaniline. The aromatic amine terminals of self-assembled monolayers (SAMs) of ATQD on glass substrates were covalently modified with an adhesive oligopeptide, cyclic Arg-Gly-Asp (RGD) (ATQD RGD). The mean height of the monolayer coating on the surfaces was approximately 3 nm, as measured by atomic force microscopy. The biocompatibility of the novel electroactive substrates was evaluated using PC12 pheochromocytoma cells, an established cell line of neural origin. The bioactive, derivatized electroactive scaffold material, ATQD-RGD, supported PC12 cell adhesion and proliferation, similar to control tissue-culture-treated polystyrene surfaces. Importantly, electroactive surfaces stimulated spontaneous neuritogenesis in PC12 cells, in the absence of neurotrophic growth factors, such as nerve growth factor (NGF). As expected, NGF significantly enhanced neurite extension on both control and electroactive surfaces. Taken together, our results suggest that the newly electroactive SAMs grafted with bioactive peptides, such as RGD, could be promising biomaterials for tissue engineering. PMID- 17845054 TI - Specific interaction between chitosan and matrix metalloprotease 2 decreases the invasive activity of human melanoma cells. AB - The crucial event in metastasis is tumor invasion which in the case of melanoma cells is dependent on matrix metalloprotease 2 (MMP2). Chitosan (MW ca. 5 x 10(5) g mol(-1), degree of acetylation ca. 30%) attenuated the invasive activity of melanoma cells in a cell-based invasion assay and reduced MMP2 activity in the supernatant of melanoma cells. While the expression level of MMP2 was not affected, the amount of MMP2 in the cell supernatant was reduced, indicating a posttranscriptional effect of chitosan on MMP2. Atomic force microscopy revealed a direct molecular interaction between MMP2 and chitosan forming a complex with a diameter of 349.0 +/- 69.06 nm and a height of 26.5 +/- 11.50 nm. Affinity chromatography revealed a high binding-specificity of MMP2 to chitosan, and a colorimetric MMP2 activity assay suggests a noncompetitive inhibition of MMP2 by chitosan. The possible use of chitosan as a new type of MMP2 inhibitor is discussed. PMID- 17845055 TI - Coactivator assembly at the promoter: efficient recruitment of SRC2 is coupled to cooperative DNA binding by the progesterone receptor. AB - A largely unsolved problem in eukaryotic gene regulation focuses on the mechanisms by which DNA-bound transcription factors recruit coactivators to a promoter. Recent work has suggested that promoter DNA acts as an allosteric ligand, serving not only to bind and localize transcription factors but also to trigger structural changes within the proteins in order to elicit coactivator recruitment. Unfortunately, a quantitative and molecular understanding of this phenomenon remains unclear. We have previously resolved the microstate interaction energetics of progesterone receptor A-isoform (PR-A) assembly at multiple promoters; here we extend this work to the role of PR-A in mediating promoter-dependent recruitment of the coactivator, SRC2. Quantitative footprinting and statistical thermodynamic modeling of PR-A:promoter interactions in the presence and absence of coactivator demonstrate that receptor binding to a single response element is maximally coupled to a 2-fold enhancement in SRC2 binding. By contrast, PR-A assembly at multiple response elements is linked to an additional 6- to 10-fold increase in SRC2 affinity. This effect arises due to a coupled reaction between SRC2 uptake and enhanced cooperative interactions between adjacently bound PR-A dimers. Put another way, increased coactivator levels stabilize a higher-order receptor-promoter complex. These results may thus not only offer a mechanism for explaining the weak transcriptional activity seen for promoters containing a single binding site and the synergistically strong activity seen for multisite promoters but also suggest that in vivo fluctuations of coactivator levels might serve as a physiological regulator of assembly for PR A (and for other nuclear receptors) at the promoter. PMID- 17845056 TI - Effect of pathogenic cysteine mutations on FGFR3 transmembrane domain dimerization in detergents and lipid bilayers. AB - Mutations in fibroblast growth factor receptors are known as the genetic basis of skeletal growth disorders. The mechanism of pathogenesis, as determined by mutation-induced changes in receptor structure, interactions, and function, is elusive. Here we study three pathogenic Cys mutations, associated with either thanatophoric dysplasia or achondroplasia, in the TM domain of fibroblast growth factor receptors 3 (FGFR3). We characterize the dimerization propensities of the mutant TM domains in detergents and in lipid bilayers, in the presence and absence of reducing agents, and compare them to previous measurements of wild type. We find that the Cys mutations increase the propensity for dimerization in detergent, with the Cys370 mutant exhibiting the highest propensity for disulfide bond formation, the Cys371 mutant having an intermediate propensity, and Cys375 the lowest. Thus, disulfide bonds readily form in detergents, with efficiency that correlates with the severity of the phenotype. In lipid bilayers, however, the Cys370 mutant, which dimerizes strongly in detergent, behaves as the wild type, suggesting that Cys370-mediated disulfide bonds do not form between the isolated TM domains in bilayers. Thus, the nature of the hydrophobic environment plays an important role in defining the structure and flexibility of transmembrane dimers. These results and previous findings from cellular studies lead us to propose a conformational flexibility mechanism of receptor stabilization as a basis for disregulated FGFR3 signaling in thanatophoric dysplasia and achondroplasia. PMID- 17845057 TI - Direct visualization of the EcoRII-DNA triple synaptic complex by atomic force microscopy. AB - Interactions between distantly separated DNA regions mediated by specialized proteins lead to the formation of synaptic protein-DNA complexes. This is a ubiquitous phenomenon which is critical in various genetic processes. Although such interactions typically occur between two sites, interactions among three specific DNA regions have been identified, and a corresponding model has been proposed. Atomic force microscopy was used to test this model for the EcoRII restriction enzyme and provide direct visualization and characterization of synaptic protein-DNA complexes involving three DNA binding sites. The complex appeared in the images as a two-loop structure, and the length measurements proved the site specificity of the protein in the complex. The protein volume measurements showed that an EcoRII dimer is the core of the three-site synaptosome. Other complexes were identified and analyzed. The protein volume data showed that the dimeric form of the protein is responsible for the formation of other types of synaptic complexes as well. The applications of these results to the mechanisms of the protein-DNA interactions are discussed. PMID- 17845059 TI - [NiFe] and [FeFe] hydrogenases studied by advanced magnetic resonance techniques. PMID- 17845058 TI - Structure of mini-B, a functional fragment of surfactant protein B, in detergent micelles. AB - Surfactant protein B (SP-B) is essential for normal lung surfactant function, which is in itself essential to life. However, the molecular basis for SP-B's activity is not understood and a high-resolution structure for SP-B has not been determined. Mini-B is a 34-residue peptide with internal disulfide linkages that is composed of the N- and C-terminal helical regions of SP-B. It has been shown to retain similar activity to full-length SP-B in certain in vitro and in vivo studies. We have used solution NMR to determine the structure of Mini-B in the presence of micelles composed of the anionic detergent sodium dodecyl sulfate (SDS). Under these conditions, Mini-B forms two alpha-helices connected by an unstructured loop. Mini-B possesses a strikingly amphipathic surface with a large positively charged patch on one face of the peptide and a large hydrophobic patch on the opposite face. A tryptophan side chain extends outward from the peptide in a position to interact with lipids at the polar/apolar interface. Interhelix interactions are stabilized by both disulfide bonds and by interleaving of hydrophobic side chains from the two helices. PMID- 17845060 TI - Investigating and exploiting the electrocatalytic properties of hydrogenases. PMID- 17845061 TI - Methanol steam reforming for hydrogen production. PMID- 17845062 TI - Targeted particulate adhesion to cellulose surfaces mediated by bifunctional fusion proteins. AB - The adhesion of particles to surfaces is an integral element in many commercial and biological applications. In this article, we report on the direct measurements of protein-mediated deposition and binding of particles to model cellulose surfaces. This system involves a family of heterobifunctional fusion proteins that bind specifically to both a red dye and cellulose. Amine-coated particles were labeled with a red dye, and a fusion protein was attached to these particles at various number densities. The strength of adhesion of a single particle to a cellulose fiber was measured using micropipette manipulation as a function of the specificity of the protein and its surface density and contact time. The frequency and force of adhesion were seen to increase with contact time in fiber experiments. The dynamics of adhesion of the functionalized particles to cellulose-coated glass slides under controlled hydrodynamic flow was explored using a flow chamber for two scenarios: detachment of bound particles and attachment of particles in suspension as a function of the shear rate and surface density of protein. Highly specific adhesion was observed. The critical shear rate for particle detachment was an increasing function of cellulose binding domain (CBD) density on particle surface. A rapid irreversible attachment of particles to cellulose was observed under flow. Using a family of proteins that were divalent for binding either the red dye or cellulose, we found that particle detachment occurred because of the failure of the cellulose-CBD bond. A comparison of fiber binding and particle detachment results suggests that forces of adhesion of particles to cellulose of up to 2 nN can be obtained with this molecular system through multiple interactions. This study, along with the adhesion simulations currently under development, forms the basis of particulate design for specific adhesion applications. PMID- 17845063 TI - Fabrication of nanoaggregates of a triple hydrophilic block copolymer by cetyltrimethylammonium chloride binding. AB - A triple hydrophilic block copolymer composed of poly(ethylene oxide), poly(sodium 2-acrylamido-2-methylpropanesulfonate), and poly(methacrylic acid) (PEO-PAMPS-PMAA) does not form a micelle by itself when it is dissolved in water. However, if the anionic PAMPS and/or PMAA blocks are electrically neutralized with a cationic surfactant, such as cetyltrimethylammonium chloride (CTAC), micelle-like nanoaggregates are obtained, where the core is formed by the insolubilized PAMPS and/or PMAA blocks. Formation of the nanoaggregates was confirmed by dynamic light scattering (DLS) measurements and scanning electron microscopy (SEM), while the binding of CTAC to PEO-PAMPS-PMAA was monitored by electrophoresis measurements. The aggregates were characterized by fluorescence spectroscopy as well as DLS and SEM. It was found that the nanoaggregates have a spherical structure, and the hydrodynamic diameter ranges from 125 to 193 nm depending on the concentrations of the PEO-PAMPS-PMAA and CTAC. The critical aggregate concentration is on the order of 10-4 g L-1 when the ionic blocks of PEO-PAMPS-PMAA are fully neutralized with CTAC. PMID- 17845064 TI - Local surface charges direct the deposition of carbon nanotubes and fullerenes into nanoscale patterns. AB - This article reports on the directed deposition of carbon nanotubes (CNTs) and fullerenes onto solid surfaces using local electrostatic fields. Arbitrary patterns of local surface charges are created by charge writing with an atomic force microscope. During the subsequent development of the sample in an aqueous suspension containing surfactant-stabilized CNTs or fullerenes, Coulomb attraction guides the positioning and alignment of these particles onto the charge patterns. The surface potential of the charge patterns provides a direct control over the particle attachment. CNTs and fullerenes precisely reproduce the charge patterns, yielding structures with a lateral resolution down to the particle diameter. PMID- 17845065 TI - Synthesis of carbon nanotubes by rolling up patterned graphene nanoribbons using selective atomic adsorption. AB - We demonstrate a new method (U.S. Patent Appl., serial no. 60/908039) for synthesizing carbon nanotubes (CNTs), using first-principles and classical molecular dynamics simulations. The single-walled nanotubes (SWNTs) are formed by folding graphene nanoribbons patterned on graphite films through adsorption of atoms of varying coverage, which introduces an external stress to drive the folding process. The diameter and chirality of SWNTs can be a priori controlled by patterning graphene nanoribbons with predefined width and direction so that the postsynthesis sorting process is eliminated. Our method allows potentially mass production of identical tubes and easy integration into device structures on a substrate. PMID- 17845066 TI - On the quenching of semiconductor quantum dot photoluminescence by proximal gold nanoparticles. AB - Luminescent quantum dots (QDs) were proven to be very effective fluorescence resonance energy transfer donors with an array of organic dye acceptors, and several fluorescence resonance energy transfer based biosensing assemblies utilizing QDs have been demonstrated in the past few years. Conversely, gold nanoparticles (Au-NPs) are known for their capacity to induce strong fluorescence quenching of conventional dye donors. Using a rigid variable-length polypeptide as a bifunctional biological linker, we monitor the photoluminescence quenching of CdSe-ZnS QDs by Au-NP acceptors arrayed around the QD surface, where the center-to-center separation distance was varied over a broad range of values (approximately 50-200 Angstrom). We measure the Au-NP-induced quenching rates for such QD conjugates using steady-state and time-resolved fluorescence measurements and examine the results within the context of theoretical treatments based on the Forster dipole-dipole resonance energy transfer, dipole-metal particle energy transfer, and nanosurface energy transfer. Our results indicate that nonradiative quenching of the QD emission by proximal Au-NPs is due to long-distance dipole metal interactions that extend significantly beyond the classical Forster range, in agreement with previous studies using organic dye-Au-NP donor-acceptor pairs. PMID- 17845067 TI - Synthesis and micrometer-scale assembly of colloidal CdSe/CdS nanorods prepared by a seeded growth approach. AB - Key limitations of the colloidal semiconductor nanorods that have been reported so far are a significant distribution of lengths and diameters as well as the presence of irregular shapes produced by the current synthetic routes and, finally, the poor ability to fabricate large areas of oriented nanorod arrays. Here, we report a seeded-growth approach to the synthesis of asymmetric core shell CdSe/CdS nanorods with regular shapes and narrow distributions of rod diameters and lengths, the latter being easily tunable up to 150 nm. These rods are highly fluorescent and show linearly polarized emission, whereby the emission energy depends mainly on the core diameter. We demonstrate their lateral alignment as well as their vertical self-alignment on substrates up to areas of several square micrometers. PMID- 17845068 TI - Seeded growth of highly luminescent CdSe/CdS nanoheterostructures with rod and tetrapod morphologies. AB - We have demonstrated that seeded growth of nanocrystals offers a convenient way to design nanoheterostructures with complex shapes and morphologies by changing the crystalline structure of the seed. By using CdSe nanocrystals with wurtzite and zinc blende structure as seeds for growth of CdS nanorods, we synthesized CdSe/CdS heterostructure nanorods and nanotetrapods, respectively. Both of these structures showed excellent luminescent properties, combining high photoluminescence efficiency (approximately 80 and approximately 50% for nanorods and nanotetrapods, correspondingly), giant extinction coefficients (approximately 2 x 10(7) and approximately 1.5 x 10(8) M(-1) cm(-1) at 350 nm for nanorods and nanotetrapods, correspondingly), and efficient energy transfer from the CdS arms into the emitting CdSe core. PMID- 17845069 TI - A molecular spectroscopic description of optical spectra of J-aggregated dyes on gold nanoparticles. AB - The extinction spectra of J-aggregated dyes on gold nanoparticles, which exhibit interferences between the plasmonic and dye resonances, are simulated by a quantum mechanical model that considers the dye transition to interact through transition-dipole coupling with a continuum of nanoparticle states. This alternative to the classical core-shell dielectric model provides the wavefunctions of the coupled molecule-nanoparticle system and qualitatively explains the enhancement of resonance Raman, fluorescence, and other light-driven processes of molecules adsorbed to nanoparticles. PMID- 17845070 TI - A balanced memory network. AB - A fundamental problem in neuroscience is understanding how working memory--the ability to store information at intermediate timescales, like tens of seconds--is implemented in realistic neuronal networks. The most likely candidate mechanism is the attractor network, and a great deal of effort has gone toward investigating it theoretically. Yet, despite almost a quarter century of intense work, attractor networks are not fully understood. In particular, there are still two unanswered questions. First, how is it that attractor networks exhibit irregular firing, as is observed experimentally during working memory tasks? And second, how many memories can be stored under biologically realistic conditions? Here we answer both questions by studying an attractor neural network in which inhibition and excitation balance each other. Using mean-field analysis, we derive a three-variable description of attractor networks. From this description it follows that irregular firing can exist only if the number of neurons involved in a memory is large. The same mean-field analysis also shows that the number of memories that can be stored in a network scales with the number of excitatory connections, a result that has been suggested for simple models but never shown for realistic ones. Both of these predictions are verified using simulations with large networks of spiking neurons. PMID- 17845071 TI - Orthologous transcription factors in bacteria have different functions and regulate different genes. AB - Transcription factors (TFs) form large paralogous gene families and have complex evolutionary histories. Here, we ask whether putative orthologs of TFs, from bidirectional best BLAST hits (BBHs), are evolutionary orthologs with conserved functions. We show that BBHs of TFs from distantly related bacteria are usually not evolutionary orthologs. Furthermore, the false orthologs usually respond to different signals and regulate distinct pathways, while the few BBHs that are evolutionary orthologs do have conserved functions. To test the conservation of regulatory interactions, we analyze expression patterns. We find that regulatory relationships between TFs and their regulated genes are usually not conserved for BBHs in Escherichia coli K12 and Bacillus subtilis. Even in the much more closely related bacteria Vibrio cholerae and Shewanella oneidensis MR-1, predicting regulation from E. coli BBHs has high error rates. Using gene-regulon correlations, we identify genes whose expression pattern differs between E. coli and S. oneidensis. Using literature searches and sequence analysis, we show that these changes in expression patterns reflect changes in gene regulation, even for evolutionary orthologs. We conclude that the evolution of bacterial regulation should be analyzed with phylogenetic trees, rather than BBHs, and that bacterial regulatory networks evolve more rapidly than previously thought. PMID- 17845072 TI - Serum amyloid P aids complement-mediated immunity to Streptococcus pneumoniae. AB - The physiological functions of the acute phase protein serum amyloid P (SAP) component are not well defined, although they are likely to be important, as no natural state of SAP deficiency has been reported. We have investigated the role of SAP for innate immunity to the important human pathogen Streptococcus pneumoniae. Using flow cytometry assays, we show that SAP binds to S. pneumoniae, increases classical pathway-dependent deposition of complement on the bacteria, and improves the efficiency of phagocytosis. As a consequence, in mouse models of infection, mice genetically engineered to be SAP-deficient had an impaired early inflammatory response to S. pneumoniae pneumonia and were unable to control bacterial replication, leading to the rapid development of fatal infection. Complement deposition, phagocytosis, and control of S. pneumoniae pneumonia were all improved by complementation with human SAP. These results demonstrate a novel and physiologically significant role for SAP for complement-mediated immunity against an important bacterial pathogen, and provide further evidence for the importance of the classical complement pathway for innate immunity. PMID- 17845073 TI - Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. AB - Siderophore biosynthesis by the highly lethal mould Aspergillus fumigatus is essential for virulence, but non-existent in humans, presenting a rare opportunity to strategize therapeutically against this pathogen. We have previously demonstrated that A. fumigatus excretes fusarinine C and triacetylfusarinine C to capture extracellular iron, and uses ferricrocin for hyphal iron storage. Here, we delineate pathways of intra- and extracellular siderophore biosynthesis and show that A. fumigatus synthesizes a developmentally regulated fourth siderophore, termed hydroxyferricrocin, employed for conidial iron storage. By inactivation of the nonribosomal peptide synthetase SidC, we demonstrate that the intracellular siderophores are required for germ tube formation, asexual sporulation, resistance to oxidative stress, catalase A activity, and virulence. Restoration of the conidial hydroxyferricrocin content partially rescues the virulence of the apathogenic siderophore null mutant Delta sidA, demonstrating an important role for the conidial siderophore during initiation of infection. Abrogation of extracellular siderophore biosynthesis following inactivation of the acyl transferase SidF or the nonribosomal peptide synthetase SidD leads to complete dependence upon reductive iron assimilation for growth under iron-limiting conditions, partial sensitivity to oxidative stress, and significantly reduced virulence, despite normal germ tube formation. Our findings reveal distinct cellular and disease-related roles for intra- and extracellular siderophores during mammalian Aspergillus infection. PMID- 17845074 TI - Hemoglobin is a co-factor of human trypanosome lytic factor. AB - Trypanosome lytic factor (TLF) is a high-density lipoprotein (HDL) subclass providing innate protection to humans against infection by the protozoan parasite Trypanosoma brucei brucei. Two primate-specific plasma proteins, haptoglobin related protein (Hpr) and apolipoprotein L-1 (ApoL-1), have been proposed to kill T. b. brucei both singularly or when co-assembled into the same HDL. To better understand the mechanism of T. b. brucei killing by TLF, the protein composition of TLF was investigated using a gentle immunoaffinity purification technique that avoids the loss of weakly associated proteins. HDL particles recovered by immunoaffinity absorption, with either anti-Hpr or anti-ApoL-1, were identical in protein composition and specific activity for T. b. brucei killing. Here, we show that TLF-bound Hpr strongly binds Hb and that addition of Hb stimulates TLF killing of T. b. brucei by increasing the affinity of TLF for its receptor, and by inducing Fenton chemistry within the trypanosome lysosome. These findings suggest that TLF in uninfected humans may be inactive against T. b. brucei prior to initiation of infection. We propose that infection of humans by T. b. brucei causes hemolysis that triggers the activation of TLF by the formation of Hpr-Hb complexes, leading to enhanced binding, trypanolytic activity, and clearance of parasites. PMID- 17845075 TI - Adaptive evolution of conserved noncoding elements in mammals. AB - Conserved noncoding elements (CNCs) are an abundant feature of vertebrate genomes. Some CNCs have been shown to act as cis-regulatory modules, but the function of most CNCs remains unclear. To study the evolution of CNCs, we have developed a statistical method called the "shared rates test" to identify CNCs that show significant variation in substitution rates across branches of a phylogenetic tree. We report an application of this method to alignments of 98,910 CNCs from the human, chimpanzee, dog, mouse, and rat genomes. We find that approximately 68% of CNCs evolve according to a null model where, for each CNC, a single parameter models the level of constraint acting throughout the phylogeny linking these five species. The remaining approximately 32% of CNCs show departures from the basic model including speed-ups and slow-downs on particular branches and occasionally multiple rate changes on different branches. We find that a subset of the significant CNCs have evolved significantly faster than the local neutral rate on a particular branch, providing strong evidence for adaptive evolution in these CNCs. The distribution of these signals on the phylogeny suggests that adaptive evolution of CNCs occurs in occasional short bursts of evolution. Our analyses suggest a large set of promising targets for future functional studies of adaptation. PMID- 17845076 TI - The inheritance of resistance alleles in multiple sclerosis. AB - Multiple sclerosis (MS) is a complex trait in which alleles at or near the class II loci HLA-DRB1 and HLA-DQB1 contribute significantly to genetic risk. HLA DRB1*15 and HLA-DRB1*17-bearing haplotypes and interactions at the HLA-DRB1 locus increase risk of MS but it has taken large samples to identify resistance HLA DRB1 alleles. In this investigation of 7,093 individuals from 1,432 MS families, we have assessed the validity, mode of inheritance, associated genotypes, and the interactions of HLA-DRB1 resistance alleles. HLA-DRB1*14-, HLA-DRB1*11-, HLA DRB1*01-, and HLA-DRB1*10-bearing haplotypes are protective overall but they appear to operate by different mechanisms. The first type of resistance allele is characterised by HLA-DRB1*14 and HLA-DRB1*11. Each shows a multiplicative mode of inheritance indicating a broadly acting suppression of risk, but a different degree of protection. In contrast, a second type is exemplified by HLA-DRB1*10 and HLA-DRB1*01. These alleles are significantly protective when they interact specifically in trans with HLA-DRB1*15-bearing haplotypes. HLA-DRB1*01 and HLA DRB1*10 do not interact with HLA-DRB1*17, implying that several mechanisms may be operative in major histocompatibility complex-associated MS susceptibility, perhaps analogous to the resistance alleles. There are major practical implications for risk and for the exploration of mechanisms in animal models. Restriction of antigen presentation by HLA-DRB1*15 seems an improbably simple mechanism of major histocompatibility complex-associated susceptibility. PMID- 17845077 TI - Evidence for transgenerational transmission of epigenetic tumor susceptibility in Drosophila. AB - Transgenerational epigenetic inheritance results from incomplete erasure of parental epigenetic marks during epigenetic reprogramming at fertilization. The significance of this phenomenon, and the mechanism by which it occurs, remains obscure. Here, we show that genetic mutations in Drosophila may cause epigenetic alterations that, when inherited, influence tumor susceptibility of the offspring. We found that many of the mutations that affected tumorigenesis induced by a hyperactive JAK kinase, Hop(Tum-l), also modified the tumor phenotype epigenetically, such that the modification persisted even in the offspring that did not inherit the modifier mutation. We analyzed mutations of the transcription repressor Kruppel (Kr), which is one of the hop(Tum-l) enhancers known to affect ftz transcription. We demonstrate that the Kr mutation causes increased DNA methylation in the ftz promoter region, and that the aberrant ftz transcription and promoter methylation are both transgenerationally heritable if Hop(Tum-l) is present in the oocyte. These results suggest that genetic mutations may alter epigenetic markings in the form of DNA methylation, which are normally erased early in the next generation, and that JAK overactivation disrupts epigenetic reprogramming and allows inheritance of epimutations that influence tumorigenesis in future generations. PMID- 17845079 TI - Bridging faultlines by valuing diversity: diversity beliefs, information elaboration, and performance in diverse work groups. AB - Although there are numerous potential benefits to diversity in work groups, converging dimensions of diversity often prevent groups from exploiting this potential. In a study of heterogeneous decision-making groups, the authors examined whether the disruptive effects of diversity faultlines can be overcome by convincing groups of the value of diversity. Groups were persuaded either of the value of diversity or the value of similarity for group performance, and they were provided with either homogeneous or heterogeneous information. As expected, informationally diverse groups performed better when they held pro-diversity rather than pro-similarity beliefs, whereas the performance of informationally homogeneous groups was unaffected by diversity beliefs. This effect was mediated by group-level information elaboration. Implications for diversity management in organizations are discussed. PMID- 17845078 TI - Irf3 polymorphism alters induction of interferon beta in response to Listeria monocytogenes infection. AB - Genetic makeup of the host plays a significant role in the course and outcome of infection. Inbred strains of mice display a wide range of sensitivities to Listeria monocytogenes infection and thus serve as a good model for analysis of the effect of genetic polymorphism. The outcome of L. monocytogenes infection in mice is influenced by the ability of this bacterium to induce expression of interferon beta mRNA, encoded in mouse by the Ifnb1 (interferon beta 1, fibroblast) gene. Mouse strains that lack components of the IFN beta signaling pathway are substantially more resistant to infection. We found that macrophages from the ByJ substrain of the common C57BL/6 inbred strain of mice are impaired in their ability to induce Ifnb1 expression in response to bacterial and viral infections. We mapped the locus that controls differential expression of Ifnb1 to a region on Chromosome 7 that includes interferon regulatory factor 3 (Irf3), which encodes a transcription factor responsible for early induction of Ifnb1 expression. In C57BL/6ByJ mice, Irf3 mRNA was inefficiently spliced, with a significant proportion of the transcripts retaining intron 5. Analysis of the Irf3 locus identified a single base-pair polymorphism and revealed that intron 5 of Irf3 is spliced by the atypical U12-type spliceosome. We found that the polymorphism disrupts a U12-type branchpoint and has a profound effect on the efficiency of splicing of Irf3. We demonstrate that a naturally occurring change in the splicing control element has a dramatic effect on the resistance to L. monocytogenes infection. Thus, the C57BL/6ByJ mouse strain serves as an example of how a mammalian host can counter bacterial virulence strategies by introducing subtle alteration of noncoding sequences. PMID- 17845080 TI - Disentangling role perceptions: how perceived role breadth, discretion, instrumentality, and efficacy relate to helping and taking charge. AB - The objective of this study was to empirically disentangle role perceptions related to organizational citizenship behavior (OCB) that have been confounded in past research, investigate their unique relationships with both an affiliative (helping) and a challenging (taking charge) form of OCB, and determine their relative importance in explaining these 2 forms of OCB. The authors also examined whether role discretion and role breadth independently moderate the procedural justice-to-OCB relationship. The authors surveyed 225 engineers in India and their direct supervisors. The results showed that 3 of the 4 facets of OCB role perception explain unique variance in either helping or taking charge, and that role breadth moderates the relationships between procedural justice and both helping and taking charge. The authors discuss implications of these findings for OCB theory and research, as well as for managerial practice. PMID- 17845081 TI - Capitalizing on one's advantages: role of core self-evaluations. AB - The authors examined (a) whether core self-evaluations in adolescence and young adulthood predict income at midlife and (b) whether people with positive core self-evaluations are more likely to capitalize on advantages resulting from family socioeconomic status and academic achievement, resulting in even higher levels of income at midcareer. The sample consisted of participants from the National Longitudinal Survey of Youth, a national probability sample that first surveyed participants in 1979. The authors found that core self-evaluations and family socioeconomic status and academic achievement predict income and that, furthermore, high core self-evaluations enhance the benefits derived from these factors. Overall, it appears that individuals with positive core self-evaluations are particularly adept at translating early advantages into later economic success. PMID- 17845082 TI - Consensus in work role requirements: the influence of discrete occupational context on role expectations. AB - Although role theory has long described how expectations shape role behavior, little empirical research has examined differences among work role requirements and how features of the discrete occupational context may influence the extent to which role expectations are shared among role holders. The authors examined consensus in work role requirements from a sample of over 20,000 incumbents across 98 occupations. They found that consensus systematically decreased as work role requirements ranged from molecular tasks to responsibilities to molar traits. In addition, they found that consensus in these work role requirements was significantly influenced by the amount of interdependence, autonomy, and routinization present in the surrounding task and social contexts. PMID- 17845083 TI - Stability and change in person-team and person-role fit over time: the effects of growth satisfaction, performance, and general self-efficacy. AB - Although considerable research has focused on various forms of person-environment fit, little research has examined how person-team and person-role fit operate over time in team contexts. To address this gap, the authors examined the dynamic nature of values-based person-team fit and person-role fit. They identified several factors that influence these fit perceptions over time. Individuals were composed into teams that worked intensively over an extended time period. Results suggest that person-team fit, when conceptualized as values congruence, is generally stable over time, but perceptions of person-role fit in teams are dynamic. Individuals' growth satisfaction and performance were positively related to increases in person-role fit over time. Furthermore, the effect of performance on person-role fit was moderated by individuals' general self-efficacy. Implications for managerial practice and future research are discussed. PMID- 17845084 TI - Beyond targets: consequences of vicarious exposure to misogyny at work. AB - The present study tested a model examining 2 indicators of a hostile interpersonal workplace climate for women-observed hostility (i.e., incivility and sexual harassment) toward women and perceived organizational unresponsiveness to sexual harassment--and how they relate to well-being and withdrawal for employees. Participants included 871 female and 831 male employees from a public university. According to structural equation analyses, observing hostility toward women and perceiving the organization as lax about harassment predict lower well being, which translates into higher organizational withdrawal for both female and male employees. Results hold even after controlling for personal mistreatment, negative affectivity, and observed hostility toward men. These findings suggest that working in a misogynistic environment can have negative effects for all employees. PMID- 17845085 TI - Personality measurement, faking, and employment selection. AB - Real job applicants completed a 5-factor model personality measure as part of the job application process. They were rejected; 6 months later they (n = 5,266) reapplied for the same job and completed the same personality measure. Results indicated that 5.2% or fewer improved their scores on any scale on the 2nd occasion; moreover, scale scores were as likely to change in the negative direction as the positive. Only 3 applicants changed scores on all 5 scales beyond a 95% confidence threshold. Construct validity of the personality scales remained intact across the 2 administrations, and the same structural model provided an acceptable fit to the scale score matrix on both occasions. For the small number of applicants whose scores changed beyond the standard error of measurement, the authors found the changes were systematic and predictable using measures of social skill, social desirability, and integrity. Results suggest that faking on personality measures is not a significant problem in real-world selection settings. PMID- 17845086 TI - The joint effects of personality and workplace social exchange relationships in predicting task performance and citizenship performance. AB - This field study examines the joint effects of social exchange relationships at work (leader-member exchange and team-member exchange) and employee personality (conscientiousness and agreeableness) in predicting task performance and citizenship performance. Consistent with trait activation theory, matched data on 230 employees, their coworkers, and their supervisors demonstrated interactions in which high quality social exchange relationships weakened the positive relationships between personality and performance. Results demonstrate the benefits of consonant predictions in which predictors and outcomes are matched on the basis of specific targets. We discuss theoretical and practical implications. PMID- 17845087 TI - Implicit and explicit personality: a test of a channeling hypothesis for aggressive behavior. AB - D. G. Winter, O. P. John, A. J. Stewart, E. C. Klohnen, and L. E. Duncan (1998) proposed that self-beliefs about personality influence the channels through which people express their implicit motives. On the basis of this hypothesis, the authors predicted that self-beliefs about aggressiveness would influence the channel(s) through which people express their aggressive motive and the justification mechanisms they use to defend expression of this motive. For example, the authors predicted that people who were implicitly prepared to rationalize a desire to harm others would engage in (a) overt aggression if they viewed themselves as aggressive or (b) passive aggression if they viewed themselves as nonaggressive. The implicit aspects of aggressiveness were measured via conditional reasoning (L. R. James et al., 2005). Results based on intramural basketball players supported the channeling hypothesis. PMID- 17845088 TI - The influence of degree of expertise and objective task complexity on perceived task complexity and performance. AB - Research on expertise has shown that nonexperts may sometimes outperform experts. Some researchers have suggested that superior performance by experts depends on the match between the experts' cognition and the demands of the task. The authors explored this issue using a quasi-experiment set in an organization. They examined how 3 sets of similar tasks that differ in their type of complexity can lead to differences in task perceptions and performance among experts, intermediates, and novices. The results suggest that experts and novices pay attention to different aspects of a task and that this affects both their perceptions of task complexity (i.e., task analyzability and variability) and their performance on the task. PMID- 17845089 TI - Integrating motivational, social, and contextual work design features: a meta analytic summary and theoretical extension of the work design literature. AB - The authors developed and meta-analytically examined hypotheses designed to test and extend work design theory by integrating motivational, social, and work context characteristics. Results from a summary of 259 studies and 219,625 participants showed that 14 work characteristics explained, on average, 43% of the variance in the 19 worker attitudes and behaviors examined. For example, motivational characteristics explained 25% of the variance in subjective performance, 2% in turnover perceptions, 34% in job satisfaction, 24% in organizational commitment, and 26% in role perception outcomes. Beyond motivational characteristics, social characteristics explained incremental variances of 9% of the variance in subjective performance, 24% in turnover intentions, 17% in job satisfaction, 40% in organizational commitment, and 18% in role perception outcomes. Finally, beyond both motivational and social characteristics, work context characteristics explained incremental variances of 4% in job satisfaction and 16% in stress. The results of this study suggest numerous opportunities for the continued development of work design theory and practice. PMID- 17845090 TI - Workplace emotions: the role of supervision and leadership. AB - In this experience sampling study, the authors examined the role of organizational leaders in employees' emotional experiences. Data were collected from health care workers 4 times a day for 2 weeks. Results indicate supervisors were associated with employee emotions in 3 ways: (a) Employees experienced fewer positive emotions when interacting with their supervisors as compared with interactions with coworkers and customers; (b) employees with supervisors high on transformational leadership experienced more positive emotions throughout the workday, including interactions with coworkers and customers; and (c) employees who regulated their emotions experienced decreased job satisfaction and increased stress, but those with supervisors high on transformational leadership were less likely to experience decreased job satisfaction. The results also suggest that the effects of emotional regulation on stress are long lasting (up to 2 hr) and not easily reduced by leadership behaviors. PMID- 17845092 TI - Combining predictors to achieve optimal trade-offs between selection quality and adverse impact. AB - The authors propose a procedure to determine (a) predictor composites that result in a Pareto-optimal trade-off between the often competing goals in personnel selection of quality and adverse impact and (b) the relative importance of the quality and impact objectives that correspond to each of these trade-offs. They also investigated whether the obtained Pareto-optimal composites continue to perform well under variability of the selection parameters that characterize the intended selection decision. The results of this investigation indicate that this is indeed the case. The authors suggest that the procedure be used as one of a number of potential strategies for addressing the quality-adverse impact problem in settings where estimates of the selection parameters (e.g., validity estimates, predictor intercorrelations, subgroup mean differences on the predictors and criteria) are available from either a local validation study or meta-analytic research. PMID- 17845091 TI - When can employees have a family life? The effects of daily workload and affect on work-family conflict and social behaviors at home. AB - This article presents a longitudinal examination of antecedents and outcomes of work-to-family conflict. A total of 106 employees participating in an experience sampling study were asked to respond to daily surveys both at work and at home, and their spouses were interviewed daily via telephone for a period of 2 weeks. Intraindividual analyses revealed that employees' perceptions of workload predicted work-to-family conflict over time, even when controlling for the number of hours spent at work. Workload also influenced affect at work, which in turn influenced affect at home. Finally, perhaps the most interesting finding in this study was that employees' behaviors in the family domain (reported by spouses) were predicted by the employees' perceptions of work-to-family conflict and their positive affect at home. PMID- 17845093 TI - Choosing the best method for local validity estimation: relative accuracy of meta analysis versus a local study versus Bayes-analysis. AB - This study assessed the relative accuracy of 3 techniques--local validity studies, meta-analysis, and Bayesian analysis--for estimating test validity, incremental validity, and adverse impact in the local selection context. Bayes analysis involves combining a local study with nonlocal (meta-analytic) validity data. Using tests of cognitive ability and personality (conscientiousness) as predictors, an empirically driven selection scenario illustrates conditions in which each of the 3 estimation techniques performs best. General recommendations are offered for how to estimate local parameters, based on true population variability and the number of studies in the meta-analytic prior. Benefits of empirical Bayesian analysis for personnel selection are demonstrated, and equations are derived to help guide the choice of a local validity technique (i.e., meta-analysis vs. local study vs. Bayes-analysis). PMID- 17845094 TI - Assessing dissimilarity relations under missing data conditions: evidence from computer simulations. AB - The extensive research examining relations between group member dissimilarity and outcome measures has yielded inconsistent results. In the present research, the authors used computer simulations to examine the impact that a methodological feature of such research, participant nonresponse, can have on dissimilarity outcome relations. Results suggest that using only survey responders to calculate dissimilarity typically results in underestimation of true dissimilarity effects and that these effects can occur even when response rates are high. PMID- 17845095 TI - Predicting the counterproductive employee in a child-to-adult prospective study. AB - The present research tested the relations between a battery of background factors and counterproductive work behaviors in a 23-year longitudinal study of young adults (N = 930). Background information, such as diagnosed adolescent conduct disorder, criminal conviction records, intelligence, and personality traits, was assessed before participants entered the labor force. These background factors were combined with work conditions at age 26 to predict counterproductive work behaviors at age 26. The results showed that people diagnosed with childhood conduct disorder were more prone to commit counterproductive work behaviors in young adulthood and that these associations were partially mediated by personality traits measured at age 18. Contrary to expectations, criminal convictions that occurred prior to entering the workforce were unrelated to counterproductive work behaviors. Job conditions and personality traits had independent effects on counterproductive work behaviors, above and beyond background factors. PMID- 17845096 TI - The role of goal orientation during expatriation: a cross-sectional and longitudinal investigation. AB - Using cross-sectional and longitudinal data from expatriates in China, the authors investigated the roles of general, work, and interaction adjustment, as well as work stress, as mediators between the antecedents (learning, proving, and avoiding goal orientations, and perceived organizational support) and expatriate outcome (job performance and premature return intention) relationships. Results indicated that goal orientations toward overseas assignments had differential relationships with expatriate job performance and premature return intention. In addition, it was found that these relationships were partially mediated by expatriate adjustment facets. Implications for expatriate adjustment research and practice are discussed. PMID- 17845097 TI - Person-organization fit and work-related attitudes and decisions: examining interactive effects with job fit and conscientiousness. AB - This study examined boundary conditions that surround the importance of perceived person-organization (P-O) fit for work-related attitudes and decisions. The authors hypothesized that P-O fit is more strongly related to satisfaction and job choice decisions when needs-supplies (N-S) job fit or demands-abilities (D-A) job fit is low, and that P-O fit is more strongly related to job choice decisions for highly conscientious individuals. Hypotheses were tested among 299 participants in a 12-week internship program. Results indicated that P-O fit was more strongly related to satisfaction when individuals experienced low N-S job fit. P-O fit was more strongly related to job choice intentions when individuals experienced low D-A job fit or were highly conscientious. Finally, P-O fit was related to job offer acceptance for highly conscientious individuals. PMID- 17845098 TI - Work characteristics, musculoskeletal disorders, and the mediating role of psychological strain: a study of call center employees. AB - The demands of the modern office are thought to contribute to the development of musculoskeletal disorders. For upper body and lower back disorders, these effects are hypothesized to be mediated by psychological strain. A study of 936 employees from 22 call centers supports this hypothesis. Using logistic regression and structural equation modeling, the authors found that the relationship of workload to upper body and lower back musculoskeletal disorders was largely accounted for by job-related strain. This mediating effect was less evident for arm disorders. Contrary to expectation, job autonomy had neither a direct nor a moderating effect on any musculoskeletal disorder. PMID- 17845099 TI - Health psychology and scientific consensus: the case of depression and cardiovascular disease. PMID- 17845101 TI - Clinician's comment on treatment of childhood overweight meta-analysis. AB - Given the prevalence and urgency of the childhood overweight problem, pediatric providers are searching for evidence-based management to translate into clinical practice, particularly in primary care. There are numerous challenges to translation and therefore to more widespread adoption of childhood overweight treatment recommendations. In this article, the authors try to bridge this gap between childhood overweight treatment research and clinical care by discussing the current evidence-based recommendations through a clinical case and by examining the challenges of translation. Looking at this issue through the lens of a clinician, the authors consider the broader social context within which childhood overweight exists, and highlight areas for further translational work. PMID- 17845100 TI - Lifestyle interventions in the treatment of childhood overweight: a meta-analytic review of randomized controlled trials. AB - CONTEXT: Evaluating the efficacy of pediatric weight loss treatments is critical. OBJECTIVE: This is the first meta-analysis of the efficacy of RCTs comparing pediatric lifestyle interventions to no-treatment or information/education-only controls. DATA SOURCES: Medline, PsycINFO, and Cochrane Controlled Trials Register. STUDY SELECTION: Fourteen RCTs targetting change in weight status were eligible, yielding 19 effect sizes. DATA EXTRACTION: Standardized coding was used to extract information on design, participant characteristics, interventions, and results. DATA SYNTHESIS: For trials with no-treatment controls, the mean effect size was 0.75 (k = 9, 95% confidence interval [CI] = 0.52-0.98) at end of treatment and 0.60 (k = 4, CI = 0.27-0.94) at follow-up. For trials with information/education-only controls, the mean ES was 0.48 (k = 4, CI = 0.13-0.82) at end of treatment and 0.91 (k = 2, CI = 0.32-1.50) at follow-up. No moderator effects were identified. CONCLUSIONS: Lifestyle interventions for pediatric overweight are efficacious in the short term with some evidence for extended persistence. Future research is required to identify moderators and mediators and to determine the optimal length and intensity of treatment required to produce enduring changes in weight status. PMID- 17845102 TI - Terminally ill patients and volunteer support: is it the right intervention? PMID- 17845104 TI - In response to Kalichman et al. (2006). Internet use and coping among those with HIV/AIDS in a mostly African American sample. PMID- 17845105 TI - Depression and distress predict time to cardiovascular disease in dementia caregivers. AB - OBJECTIVE: This study assessed the impact of depressive symptoms and distress from patient problem behaviors on time to developing a diagnosis of cardiovascular disease (CVD) in a sample of 643 dementia family caregivers. DESIGN: A longitudinal, prospective design was used. Over an 18-month period, caregivers free from a CVD diagnosis at baseline were assessed at 6, 12, and 18 month follow-ups for the onset of CVD. MAIN OUTCOME MEASURES: Days to the onset of CVD was the primary outcome. RESULTS: Over the length of the study, 32 participants (5%) reported a diagnosis of CVD. After adjusting for sociodemographic and health factors (e.g., high blood pressure, age, smoking history), greater depressive symptoms (p = .040) and distress from patient problem behaviors (p = .034) were significant predictors of time to CVD diagnosis. CONCLUSION: This study suggests that increased depressive symptoms and reaction to patient problem behaviors (i.e., distress) may increase caregivers' risk for experiencing negative health outcomes, specifically CVD. PMID- 17845106 TI - Why do people with an anxiety disorder utilize more nonmental health care than those without? AB - OBJECTIVE: It is unclear why nonmental healthcare utilization is greater among those with psychological problems. The authors examined healthcare utilization in HMO patients to determine whether greater utilization in anxiety disorder (AD) patients was explained by anxiety symptoms (increasing sensitivity to physical symptoms) or comorbid illness (causing greater need for services). DESIGN: Patients were randomly selected from the database of a multi-specialty practice and 1,041 completed a survey assessing psychological symptoms, health behaviors, and demographics. Anxiety symptoms were assessed by questionnaire and the presence of an AD was determined from the medical chart. Healthcare encounters and medication use were abstracted from medical charts and HMO claims data. MAIN OUTCOME MEASURES: Healthcare utilization. RESULTS: Both AD and anxiety symptoms predicted utilization, but symptoms were not associated with utilization in a model that also included AD. Comorbid illness was significantly associated with utilization independent of AD and somewhat reduced the strength of the AD utilization association. The results were replicated in comparison of those with any psychiatric disorder to those without. CONCLUSION: Among those with AD, greater utilization is not explained by anxiety symptoms but is partly explained by greater comorbid illness. Further study is needed to understand excess healthcare utilization among AD patients. PMID- 17845107 TI - Reduction in disability in a randomized controlled trial of telephone administered cognitive-behavioral therapy. AB - OBJECTIVE: The authors examined the efficacy of telephone-administered cognitive behavioral therapy (T-CBT) and telephone-administered supportive emotion-focused therapy (T-SEFT) in reducing disability among disabled patients with multiple sclerosis and depression. Telephone administration of therapy allowed care to be delivered to a more disabled population. This is a secondary analysis of a randomized controlled trial; the primary outcome results for depression are reported in D. C. Mohr, S. L. Hart, L. Julian, C. Catledge, L. Honos-Webb, L. Vella, et al. (2005). DESIGN: A randomized controlled trial, comparing 16 weeks of T-CBT with T-SEFT. MAIN OUTCOME MEASURES: Disability was measured using Guy's Neurological Disability Scale; fatigue was measured using the Fatigue Impact Scale; depression was measured using the Hamilton Depression Rating Scale and the Beck Depression Inventory-II. RESULTS: Patients in both treatments showed significant improvements in disability and fatigue. These improvements were related to reductions in depression. T-CBT produced significantly greater decreases in disability and fatigue, compared with T-SEFT, even after controlling for depression. The greater benefit of T-CBT on disability was mediated by physical fatigue. CONCLUSION: These findings support the hypothesis that significant reductions in disability can be achieved by reducing depression in patients with multiple sclerosis. There was also evidence that further reductions could be achieved through CBT-specific interventions that include a focus on symptoms such as fatigue management. PMID- 17845108 TI - The role of familism in stress and coping processes among African American and White dementia caregivers: effects on mental and physical health. AB - OBJECTIVE: To explore how familism, burden, and coping styles mediate the relationships between ethnicity and the mental and physical health of caregivers. DESIGN: A probability sample of 65 White and 95 African Americans respondents caring for an older family member with dementia was used to test hypotheses from a sociocultural stress and coping model using path analysis. MAIN OUTCOME MEASURES: Measures of caregivers' health included subjective health, self reported diseases, blood pressure, and heart rate. Mental health measures included self-reported depression and psychological symptoms. RESULTS: Contrary to the hypothesis, familism had an adverse effect on outcomes and was related to low education levels rather than to African American ethnicity. A buffering effect of active coping between being African American and diastolic blood pressure was found even after controlling for levels of education. CONCLUSIONS: Findings supported a core stress and coping model in which more behavior problems of care recipients were associated with poorer mental health of caregivers via greater burden and more use of avoidant coping. Results also demonstrate that this core model can be extended to physical health. PMID- 17845109 TI - Osteoporosis prevention among young women: psychosocial models of calcium consumption and weight-bearing exercise. AB - OBJECTIVE: To examine the putative determinants of two osteoporosis-preventive behaviors, calcium consumption and weight-bearing exercise, in 2 samples of young women (Sample 1, n = 202; Sample 2, n = 209). A common psychosocial model of both behaviors, comprising the health belief model and augmented with constructs drawn from social cognitive theory and the theory of planned behavior, was developed, tested, and replicated. DESIGN: A prospective 2-panel design was used. Baseline data were obtained in fall 1997 for Sample 1 and in spring 2002 for Sample 2. Behavioral follow-up data were obtained 6 months after initial data collection for both samples. MAIN OUTCOME MEASURES: Baseline measures of behavioral intentions served as proximal outcomes. Behavioral measures obtained 6 months later served as distal outcomes. RESULTS: Perceived barriers and self-efficacy directly predicted intentions to consume calcium and to exercise. Descriptive norms predicted intentions, in part indirectly through barriers and self efficacy. Constructs specific to osteoporosis (e.g., susceptibility, severity) did not contribute to prediction. With initial behavior controlled, intentions to consume calcium and to exercise predicted the corresponding behaviors measured 6 months later; intentions fully mediated the relationship of model constructs to behavior. CONCLUSION: Health beliefs associated with a negative health outcome, here osteoporosis, distal to young women's lives did not contribute to prediction. In contrast, constructs related to the current behaviors of calcium consumption and weight-bearing exercise (barriers, self-efficacy, norms) were highly predictive. Implications for behavioral interventions are discussed. PMID- 17845110 TI - Characteristics of Air Force personnel who choose pharmacological aids for smoking cessation following an involuntary tobacco ban and tobacco control program. AB - OBJECTIVE: The objective of this study was to compare characteristics of smokers who did and did not report use of cessation aids as part of a tobacco control program in a military setting (n = 8994). DESIGN: The study is a longitudinal epidemiological study where the relationship between smoking status at follow-up and use of pharmacologic aids to quit smoking were assessed. MAIN OUTCOME MEASURES: Smoking cessation, post baseline use of cessation aids to quit smoking. RESULTS AND CONCLUSIONS: Individuals remaining abstinent were 70% less likely to have used NRT/pharmacological aids compared to those that relapsed. NRT/pharmacological aid users were more likely to report plans to smoke after military training, to have friends who smoke, and to accept a cigarette from a friend. NRT/pharmacological aid users were more likely to believe that using NRT was safer than smoking and to have engaged in harm reduction strategies. Our findings suggest that selection bias related to such characteristics may explain some of the discrepancies between effect sizes reported in efficacy compared to effectiveness studies of NRT and smoking outcomes currently reported in the literature. PMID- 17845111 TI - Expectancy priming of smoking cessation messages enhances the placebo effect of tailored interventions. AB - OBJECTIVE: Previous research (Webb, Simmons, & Brandon, 2005) suggested that smokers' reactions to self-help materials were more positive if they believed that the materials had been personally tailored to their individual characteristics and if they held expectancies that tailored interventions are superior to standard, or generic, interventions. The authors' objective in the current study was to replicate and extend this research by testing the efficacy expectancy priming before intervention delivery. DESIGN: In a 2 x 2 factorial experiment, 210 smokers (M = 23 cigarettes/day) recruited from the community (62% female; 92% Caucasian; mean age = 49) were randomly assigned to 1 of 4 conditions: placebo-tailored intervention/no priming, placebo-tailored intervention/priming, standard intervention/no priming, or standard intervention/priming. The tailoring-related expectancies of participants' in the priming conditions were primed before they were presented with the respective intervention booklets. MAIN OUTCOME MEASURES: Content evaluations, readiness to quit smoking, cessation self-efficacy, smoking-related knowledge, and progress toward quitting (behavior changes). Assessments occurred by mail at baseline and at 1-month postintervention. RESULTS: Similar to the earlier study, the placebo tailored booklets produced superior evaluations and smoking-related cognitive and behavioral changes. Moreover, the pretreatment expectancy priming successfully altered participants' tailoring-related expectancies and also produced superior evaluations and outcomes. CONCLUSION: Findings support a causal role of tailoring related expectancies on the efficacy of tailored interventions and suggest that interventions can be enhanced via expectancy priming. PMID- 17845112 TI - Sexual behavior in young adulthood: a population-based twin study. AB - OBJECTIVE: With behavior genetic analyses of data from young adult twins, we evaluated theoretical perspectives that differentially emphasize biological dispositions, social/cultural factors, or universal pathways to explain individual differences in sexual behaviors. DESIGN: We fit biometric sex limitation models to three aspects of sexual behavior reported by 4,925 Finnish twins ages 23-27. MAIN OUTCOME MEASURE: From a postal questionnaire, we obtained self-report information on initiation/abstinence of sexual intercourse, onset age, and number of sexual partners. RESULTS: Genetic and non-shared environmental influences were significant for all three measures. There were trends for common environmental influences on initiation and, in females, age at first intercourse. Some differential effects in males and females were found. Results comparing onset age and number of partners among experienced twins from pairs concordant and discordant for initiation found genetic and environmental influences on initiation/abstinence overlapped those found for the other aspects of sexual behavior. CONCLUSIONS: These results document genetic variation in individual differences in sexual behavior of young adults. Incorporating genetic dispositions into integrated models of sexual behavior will facilitate more effective health promotion and risk taking intervention. PMID- 17845113 TI - The influence of state and trait affect on HIV risk behaviors: a daily diary study of MSM. AB - OBJECTIVE: To characterize the influence of state and trait affect on HIV risk behaviors. DESIGN: Men who have sex with men (N = 155) completed reports of trait affect and daily reports of affect and sexual behaviors each night for up to 30 days. MAIN OUTCOME MEASURES: Analyses focused on the role of state and trait positive activation (PA), negative activation (NA), anxious arousal (AA), and sexual activation (SA) on sexual risk taking, operationalized as having a sex partner, a partner-related risk composite, and an HIV risk behavior composite. RESULTS: State SA was positively associated with having a sex partner and HIV risk behaviors; trait SA was positively associated with partner-related risk. State AA was negatively associated with having a sex partner and positively associated with HIV risk behaviors. Trait AA had a negative association with partner-related risk and moderated the effects of state AA. State PA was negatively associated with HIV risk behaviors, and trait PA had a main effect on having a sex partner. NA had no significant trait or state effects. CONCLUSION: These data suggest a role for multiple affective states in sexual risk taking. Models of HIV risk-taking behaviors should be extended to include affective processes. PMID- 17845114 TI - Perceived antigay discrimination and physical health outcomes. AB - OBJECTIVE: Theories of minority stress posit that experiences of discrimination are stressful events with the potential to cause mental and physical illness. Although some empirical studies have demonstrated a positive linear association between perceived discrimination and a variety of health outcomes, 2 studies of African Americans have revealed that those of lower occupational status who report no discrimination have higher tonic blood pressure compared with those who report modest amounts of discrimination. The authors of the present study sought to determine if this provocative pattern of findings could be replicated using a different population and different health outcomes. DESIGN: Gay and bisexual men (n = 361) were recruited through outreach to venues and community events and through advertising in local publications. They responded to survey questions using a self-administered paper questionnaire, the Internet, or a telephone. MAIN OUTCOME MEASURES: Men self-reported their frequency of nonprescription medication use, number of physician visits, and number of sick days from work during the past year. RESULTS: Perceived discrimination interacted with participant education, yielding an association between discrimination and health outcomes that was curvilinear (U-shaped) among men with lower education and an association that was positive among men with relatively higher education. CONCLUSION: This unusual pattern of results in gay and bisexual men replicates the findings from previous research with African American men and suggests that failing to recognize or acknowledge discrimination can have negative health consequences for some individuals from marginalized groups. PMID- 17845115 TI - Protective buffering and emotional desynchrony among spousal caregivers of cancer patients. AB - OBJECTIVE: To examine protective buffering and emotional desynchrony among spousal caregivers of cancer survivors. DESIGN: Repeated measures; 42 caregivers engaged in 2 videotaped, oral emotional expression exercises: 1 in the presence of their patient and 1 in the absence of their patient. MAIN OUTCOME MEASURES: Felt emotion (self-report) and expressed emotion (lexical expression or words uttered and coder-derived facial expression). Other measures assessed mental and physical health, dyadic satisfaction, and dispositional emotional inhibition. RESULTS: Protective buffering differed by communicative channel (lexical vs. facial). Caregivers' facial expressions were more positive when the patient was present versus absent. In contrast, the valence of caregivers' words did not differ per patient presence. Facial protective buffering was unrelated to health and dyadic outcomes. Lexical protective buffering was inversely related to both caregiver and patient marital satisfaction. Dispositional emotional inhibition was inversely related to caregiver mental health and marital satisfaction. Desynchrony occurred when the patient was present but was counter to prediction; felt emotion was more positive than expressed emotion. CONCLUSION: Results provide behavioral evidence of facial protective buffering. To the extent that lexical buffering occurs, it poses a dyadic risk, and chronic inhibition poses both psychological and dyadic risks. Future research is needed to refine the operational definition of desynchrony and to examine the biopsychosocial sequelae of buffering. PMID- 17845116 TI - Relationship commitment and its implications for unprotected sex among impoverished women living in shelters and low-income housing in Los Angeles County. AB - OBJECTIVE: To examine how relationship commitment among impoverished women is associated with their frequency of unprotected sex. DESIGN: Cross-sectional analyses were conducted on survey data from a probability sample of 445 women initially sampled from shelters and low-income housing in Los Angeles County. MAIN OUTCOME MEASURE: Frequency of unprotected sex in a typical month was derived as the product of 2 items: how often the woman had sex with her partner in a typical month and how often a male condom was used. RESULTS: For both sheltered and housed women, relationship commitment predicted more frequent engagement in unprotected sex with their partner, even after controlling for the type of relationship (primary vs. casual). However, this association could not be accounted for by perceived partner monogamy, ability to refuse unwanted sex, perceived HIV susceptibility, and condom use self-efficacy. Among housed women only, never asking the partner to use a condom partially accounted for more frequent engagement in unprotected sex among women with stronger relationship commitment. CONCLUSION: Results emphasize the importance of relationship commitment issues in HIV prevention interventions with impoverished women, and the need for a better understanding of relationship commitment and its influence on condom use in this population. PMID- 17845117 TI - Changes in HIV treatment beliefs and sexual risk behaviors among gay and bisexual men, 1997-2005. AB - OBJECTIVE: Beliefs about HIV treatment effectiveness and the impact of HIV treatments on HIV transmission risks were initially related to sexual risk-taking in the late 1990s when multidrug HIV treatments first became available. This study examined changes in beliefs about the effects of HIV treatment for preventing HIV transmission and their association to sexual risk behaviors between the years 1997 and 2005. DESIGN: Anonymous surveys were administered to a convenience sample of gay and bisexual men attending a large community event in Atlanta, Georgia in 1997 (N = 498) and again at the same community event in 2005 (N = 448). Analyses were performed for men living with HIV/AIDS and for men who have not been diagnosed with HIV/AIDS. MAIN OUTCOME MEASURES: Rates of unprotected anal intercourse in the previous 3 months. RESULTS: There were significant increases in high-risk sexual practices that coincided with increased beliefs that HIV treatments can reduce the chance of transmitting HIV. However, optimistic beliefs about the health benefits of HIV treatments decreased over the 8 years and were not related to risk behaviors. CONCLUSIONS: Beliefs about how HIV treatments impact HIV infectiousness remain associated with HIV transmission risk behavior and interventions targeting at-risk as well as HIV-positive men who have sex with men must directly address these beliefs and perceptions. PMID- 17845118 TI - Development and validation of the Inventory of Depression and Anxiety Symptoms (IDAS). AB - The authors describe a new self-report instrument, the Inventory of Depression and Anxiety Symptoms (IDAS), which was designed to assess specific symptom dimensions of major depression and related anxiety disorders. They created the IDAS by conducting principal factor analyses in 3 large samples (college students, psychiatric patients, community adults); the authors also examined the robustness of its psychometric properties in 5 additional samples (high school students, college students, young adults, postpartum women, psychiatric patients) who were not involved in the scale development process. The IDAS contains 10 specific symptom scales: Suicidality, Lassitude, Insomnia, Appetite Loss, Appetite Gain, Ill Temper, Well-Being, Panic, Social Anxiety, and Traumatic Intrusions. It also includes 2 broader scales: General Depression (which contains items overlapping with several other IDAS scales) and Dysphoria (which does not). The scales (a) are internally consistent, (b) capture the target dimensions well, and (c) define a single underlying factor. They show strong short-term stability and display excellent convergent validity and good discriminant validity in relation to other self-report and interview-based measures of depression and anxiety. PMID- 17845119 TI - Retrospective ratings of ADHD symptoms made at young adulthood by clinic-referred boys with ADHD-related problems, their brothers without ADHD, and control participants. AB - Retrospective childhood attention-deficit/hyperactivity disorder (ADHD) symptoms are required to diagnosis adult ADHD, but the validity of self-rated symptoms across time is questionable. Here, boys with ADHD-related problems, their brothers without ADHD, and former schoolmates rated themselves during young adulthood for ages 9, 14, and 19. Brothers rated probands retrospectively at the same ages. The young adults referred as children for ADHD (a) acknowledged childhood symptoms; (b) described improvement over time; (c) did not differ from brothers or controls on most self-ratings of young adult symptoms; (d) rated themselves as more symptomatic at age 9, but less symptomatic at age 19, than their brothers rated them; and (e) agreed only to some degree with brothers' ratings of probands' aggression (median correlation = .22). Probands' ratings showed limited agreement with judges' symptom ratings (median correlation = .16) and young adult follow-up examiners' ratings (median correlation = .14). These findings are not accounted for solely by changes in informants, nor by the course of ADHD psychopathology. They suggest some stability but limited internal consistency and validity for retrospective ADHD ratings by probands and brothers. PMID- 17845120 TI - The Disgust Scale: item analysis, factor structure, and suggestions for refinement. AB - In the 4 studies presented (N = 1,939), a converging set of analyses was conducted to evaluate the item adequacy, factor structure, reliability, and validity of the Disgust Scale (DS; J. Haidt, C. McCauley, & P. Rozin, 1994). The results suggest that 7 items (i.e., Items 2, 7, 8, 21, 23, 24, and 25) should be considered for removal from the DS. Secondary to removing the items, exploratory and confirmatory factor analyses revealed that the DS taps 3 dimensions of disgust: Core Disgust, Animal Reminder Disgust, and Contamination-Based Disgust. Women scored higher than men on the 3 disgust dimensions. Structural modeling provided support for the specificity of the 3-factor model, as Core Disgust and Contamination-Based Disgust were significantly predictive of obsessive- compulsive disorder (OCD) concerns, whereas Animal Reminder Disgust was not. Results from a clinical sample indicated that patients with OCD washing concerns scored significantly higher than patients with OCD without washing concerns on both Core Disgust and Contamination-Based Disgust, but not on Animal Reminder Disgust. These findings are discussed in the context of the refinement of the DS to promote a more psychometrically sound assessment of disgust sensitivity. PMID- 17845121 TI - Longitudinal construct validity of Brief Symptom Inventory subscales in schizophrenia. AB - Longitudinal validity of Brief Symptom Inventory subscales was examined in a sample (N = 318) with schizophrenia-related illness measured at baseline and every 6 months for 3 years. Nonlinear factor analysis of items was used to test graded response models (GRMs) for subscales in isolation. The models varied in their within-time and between-times parameter constraints, with the homogeneous model being the least constrained, followed by the 2-parameter GRM and 1 parameter GRM. Results show that 4 subscales (Interpersonal Sensitivity, Hostility, Paranoid Ideation, Psychoticism) were consistent with the 1-parameter GRM, and 5 subscales (Somatization, Obsessive-Compulsive, Depression, Anxiety, Phobic Anxiety) were consistent with the 2-parameter GRM. There is evidence that the 9 subscales may be validly used to study change in single constructs over time. PMID- 17845122 TI - Self-Injurious Thoughts and Behaviors Interview: development, reliability, and validity in an adolescent sample. AB - The authors developed the Self-Injurious Thoughts and Behaviors Interview (SITBI) and evaluated its psychometric properties. The SITBI is a structured interview that assesses the presence, frequency, and characteristics of a wide range of self-injurious thoughts and behaviors, including suicidal ideation, suicide plans, suicide gestures, suicide attempts, and nonsuicidal self-injury (NSSI). This initial study, based on the administration of the SITBI to 94 adolescents and young adults, suggested that the SITBI has strong interrater reliability (average kappa = .99, r = 1.0) and test-retest reliability (average kappa = .70, intraclass correlation coefficient = .44) over a 6-month period. Moreover, concurrent validity was demonstrated via strong correspondence between the SITBI and other measures of suicidal ideation (average kappa = .54), suicide attempt (kappa = .65), and NSSI (average kappa = .87). The authors concluded that the SITBI uniformly and comprehensively assesses a wide range of self-injury-related constructs and provides a new instrument that can be administered with relative ease in both research and clinical settings. PMID- 17845123 TI - The validity and reliability of the Violence Risk Scale-Sexual Offender version: assessing sex offender risk and evaluating therapeutic change. AB - The Violence Risk Scale-Sexual Offender version (VRS-SO) is a rating scale designed to assess risk and predict sexual recidivism, to measure and link treatment changes to sexual recidivism, and to inform the delivery of sexual offender treatment. The VRS-SO comprises 7 static and 17 dynamic items empirically or conceptually linked to sexual recidivism. Dynamic items with higher ratings identify treatment targets linked to sexual offending. A modified stages of change model assesses the offender's treatment readiness and change. File-based VRS-SO ratings were completed on 321 sex offenders followed up an average of 10 years post-release. VRS-SO scores predicted sexual and nonsexual violent recidivism post-release and demonstrated acceptable interrater reliability and concurrent validity. A factor analysis of the dynamic items generated 3 factors labeled Sexual Deviance, Criminality, and Treatment Responsivity, all of which predicted sexual recidivism and were differentially associated with different sex offender types. The dynamic items together made incremental contributions to sexual recidivism prediction after static risk was controlled for. Positive changes in the dynamic items, measured at pre- and posttreatment, were significantly related to reductions in sexual recidivism after risk and follow-up time were controlled for, suggesting that dynamic items are indeed dynamic or changeable in nature. PMID- 17845124 TI - A taxometric analysis of the Psychopathy Checklist: Screening Version (PCL:SV): further evidence of dimensionality. AB - A taxometric analysis of the Psychopathy Checklist: Screening Version (PCL:SV; S. D. Hart, D. N. Cox, & R. D. Hare, 1995) was performed on a group of 2,250 male and female forensic/psychiatric patients and jail/prison inmates. The 4 PCL:SV facet scores (Interpersonal, Affective, Impulsive Lifestyle, Antisocial Behavior) served as indicators in this study, and the data were analyzed with 3 principal taxometric procedures--mean above minus below a cut, maximum eigenvalue, and latent mode factor analysis. The results show evidence of dimensional structure on the PCL:SV in the full sample as well as in all 8 subsamples (men, women, Whites, Blacks, hospital patients, jail/prison inmates, file review with an interview, file review without an interview). These findings corroborate recent taxometric research on the Psychopathy Checklist-Revised (R. D. Hare, 1991, 2003) in which results have been largely dimensional in nature. It is concluded that scores on the PCL:SV differ quantitatively as points on a dimension (high vs. low psychopathy) rather than partitioning into qualitatively distinct categories of behavior (psychopath vs. nonpsychopath). PMID- 17845125 TI - Virtual reality for the psychophysiological assessment of phobic fear: responses during virtual tunnel driving. AB - An overall assessment of phobic fear requires not only a verbal self-report of fear but also an assessment of behavioral and physiological responses. Virtual reality can be used to simulate realistic (phobic) situations and therefore should be useful for inducing emotions in a controlled, standardized way. Verbal and physiological fear reactions were examined in 15 highly tunnel-fearful and 15 matched control participants in 3 virtual driving scenarios: an open environment, a partially open tunnel (gallery), and a closed tunnel. Highly tunnel-fearful participants were characterized by elevated fear responses specifically during tunnel drives as reflected in verbal fear ratings, heart rate reactions, and startle responses. Heart rate and fear ratings differentiated highly tunnel fearful from control participants with an accuracy of 88% and 93%, respectively. Results indicate that virtual environments are valuable tools for the assessment of fear reactions and should be used in future experimental research. PMID- 17845126 TI - Development and validation of the Smoking Expectancy Scale for Adolescents. AB - This study assessed the factor structure, internal consistency, and concurrent validity of the Smoking Expectancies Scale for Adolescents (SESA) using 717 Australian adolescents (87% nonsmokers, 11% current smokers, and 2% ex-smokers). Exploratory factor analysis of SESA yielded 8 factors. Confirmatory factor analysis indicated that the 8-factor model, and also a 2nd-order cost-benefit model, fit the data significantly better than 4 alternatives. Validation analyses revealed the 8-factor model explained 26% to 32% of the variance in adolescent cigarette use, smoking intentions, smoking subjective norms, and peer smoking. The 2nd-order model explained 12% to 17% of the variance in these same variables. PMID- 17845127 TI - Psychometric properties of eating disorder instruments in Black and White young women: internal consistency, temporal stability, and validity. AB - Most of the major instruments in the eating disorder field have documented psychometric support only in predominantly White samples. The current study examined the internal consistency, temporal stability, and convergent and discriminant validity of a variety of eating disorder measures in Black (n = 97) and White (n = 179) female undergraduates. Internal consistency coefficients were good (>.76) for all measures for both groups. Temporal stability across 5 months was also adequate in both groups, but with evidence for dietary restraint and subjective binge eating being less stable in Black women (e.g., for the Restraint subscale of the Three-Factor Eating Questionnaire [TFEQ], r = .63 for Black women and r = .82 for White women). Scores on the bulimic symptoms and dietary restraint instruments converged and diverged in a theoretically consistent pattern. Findings suggest these eating disorder measures are reliable (internally consistent; temporally stable over 5 months) and that the bulimic symptom measures of the Bulimia Test-Revised, the Bulimia subscale of the Eating Disorder Inventory, and the dietary restraint measures from the Eating Disorder Examination-Questionnaire and TFEQ demonstrate convergent and discriminant validity in Black college women. PMID- 17845128 TI - The content validity of juvenile psychopathy: an empirical examination. AB - This study examined the content validity of a juvenile psychopathy measure, the Childhood Psychopathy Scale (CPS; D. R. Lynam, 1997), based on a downward translation of an adult instrument, the Hare Psychopathy Checklist-Revised (PCL R; R. D. Hare, 1991). The CPS was compared with two other indices of juvenile psychopathy: (a) an index derived from expert ratings and (b) an empirical index based on correlations with adult psychopathy. The 100 items of the Common Language Q-Sort (CLQ; A. Caspi et al., 1992) provided a common metric for the comparison. Psychopathy and personality were assessed at age 13 years with the mother-reported CPS and the CLQ. Psychopathy was assessed at age 24 years with the interviewer-rated Psychopathy Checklist: Screening Version (PCL:SV; S. D. Hart, D. N. Cox, & R. D. Hare, 1995). Data from over 250 participants of the middle sample of the Pittsburgh Youth Study were used to examine these relations. Item content analyses demonstrated considerable overlap among the three indices, indicating that the downward translation utilizes criteria similar to those of experts and the empirically-derived measure. In addition, these indices, even after removing overlapping items, demonstrated considerable convergence, also supporting the content validity of the downward translation. These results suggest that the downward translation method is adequate for understanding the juvenile psychopathy construct. PMID- 17845129 TI - Locally advanced breast carcinoma treated with neoadjuvant chemotherapy: are the changes in serum levels of YKL-40, MMP-2 and MMP-9 correlated with tumor response? AB - Serum levels of YKL-40, MMP-2 and MMP-9 in 27 patients with locally advanced breast carcinoma received neoadjuvant chemotherapy were measured. All patients underwent neoadjuvant chemotherapy named as FAC protocol (5-Fluorouracil, Doxorubicin and Cyclophosphamide) with 21 days interval. There was 26,7% decrease in mean serum YKL-40 levels (from 146,4 microg/ml to 107,3 microg/ml) in clinically responsive group. This level was almost unchanged in non-responsive group (P>0, 05). There was 42, 1% decrease in mean serum YKL-40 levels (from 173,1 microg/ml to 98, 8 microg/ml) in pathologically responsive group. This decrease was more dramatic in patients with complete pathological response (70, 2%). However, this level was slightly increased in non-responsive group. Changes in serum levels of MMP-2 and MMP-9 were not found to be associated with tumor response. Serum measurement of YKL-40 can be a helpful tool to predict pathological tumor response in breast cancer patients with neoadjuvant chemotherapy but not MMP-2 and MMP-9. PMID- 17845130 TI - Safety of arylsulfatase A overexpression for gene therapy of metachromatic leukodystrophy. AB - Successful gene therapy approaches for metachromatic leukodystrophy (MLD), based either on hematopoietic stem/progenitor cells (HSPCs) or direct central nervous system (CNS) gene transfer, highlighted a requirement for high levels of arylsulfatase A (ARSA) expression to achieve correction of disease manifestations in the mouse model. Full assessment of the safety of ARSA expression above physiological levels thus represents a prerequisite for clinical translation of these approaches. Here, using lentiviral vectors (LVs), we generated two relevant models for the stringent evaluation of the consequences of ARSA overexpression in transduced cells. We first demonstrated that ARSA overexpression in human HSPCs does not affect their clonogenic and multilineage differentiation capacities in clonogenic assays and in a neonatal hematochimeric mouse model. Further, we studied ARSA overexpression in all body tissues by generating transgenic mice overexpressing the ARSA enzyme by LV up to 15-fold above the normal range and carrying multiple copies of LV in their genome. Characterization of these mice demonstrated the safety of ARSA overexpression in two main gene therapy targets, HSPCs and neurons, with maintenance of the complex functions of the hematopoietic and nervous system in the presence of supraphysiological enzyme levels. The activity of other sulfatases dependent on the same common activator, sulfatase modifying factor-1 (SUMF1), was tested in ARSA-overexpressing HSPCs and in transgenic mice, excluding the occurrence of saturation phenomena. Overall, these data indicate that from the perspective of clinical translation, therapeutic levels of ARSA overexpression can be safely achieved. Further, they demonstrate an experimental platform for the preclinical assessment of the safety of new gene therapy approaches. PMID- 17845131 TI - What is the functional significance of the unique location of glutaredoxin 1 (GRx1) in the intermembrane space of mitochondria? AB - Glutaredoxins (GRx) catalyze reversible protein glutathionylation. They are implicated in sulfhydryl homeostasis and regulation of redox signal transduction, controlling various cellular processes like DNA synthesis, defense against oxidative stress, apoptosis signaling, and DNA-binding of transcription factors. Two isoforms of GRx are well characterized in mammals: GRx1, the "cytosolic" form, and GRx2, the "mitochondrial" form. Here we report documentation of GRx1 in mitochondria, localized exclusively in the intermembrane space and segregated from GRx2, localized exclusively in the mitochondrial matrix. We hypothesize that GRx1 and GRx2 in their unique locations regulate different functions of the mitochondria via reversible S-glutathionylation. PMID- 17845132 TI - Protective functions of heme oxygenase-1 and carbon monoxide in the respiratory system. AB - The respiratory system, including the lung and upper airways, succumbs to injury and disease through acute or chronic exposures to adverse environmental agents, in particular, those that promote increased oxidative or inflammatory processes. Cigarette smoke and other forms of particulate or gaseous air pollution, allergens, microorganisms infections, and changes in inspired oxygen may contribute to lung injury. Among the intrinsic defenses of the lung, the stress protein heme oxygenase-1 constitutes an inducible defense mechanism that can protect the lung and its constituent cells against such insults. Heme oxygenases degrade heme to biliverdin-IXalpha, carbon monoxide, and iron, each with candidate roles in cytoprotection. At low concentrations, carbon monoxide can confer similar cyto and tissue-protective effects as endogenous heme oxygenase-1 expression, involving antioxidative, antiinflammatory, antiproliferative, and antiapoptotic effects. Lung protection by heme oxygenase-1 or its enzymatic reaction products has been demonstrated in vitro and in vivo in a number of pulmonary disease models, including acute lung injury, cigarette smoke-induced lung injury/chronic obstructive pulmonary disease, interstitial lung diseases, ischemia/reperfusion injury, and asthma/airway inflammation. This review summarizes recent findings on the functions of heme oxygenase-1 in the respiratory system, with an emphasis on possible roles in disease progression and therapies. PMID- 17845133 TI - Changing faces of heme oxygenases. PMID- 17845134 TI - Asthma genetics: from linear to multifactorial approaches. AB - Asthma risk has a clear hereditary component but, unexpectedly, the majority of reported associations between genetic variants and asthma have not been consistently replicated across studies. Methodological flaws have been indicated as a possible explanation for these inconsistencies. However, an alternative explanation is that the effects of genetic variants depend on other factors whose frequency and distribution vary, both across individuals and across populations. Within this framework, we review recent advances in asthma genetics and conclude that a paradigm shift is needed, because a static model in which the DNA sequence is associated with disease risk in a linear fashion fails to consider the interdependence of the diverse components of asthma risk. We propose an integrated approach, linking sequence variation to specific phenotypic manifestations of the disease by taking into account concurrent influences from biological systems and environmental factors that interact within specific developmental windows of opportunity. PMID- 17845135 TI - Childhood obesity: adrift in the "limbic triangle". AB - The prevalence and severity of childhood obesity have increased steadily over the past three decades. The human species evolved to rigorously defend its lower limit for weight and adiposity but is tolerant of the upper limit, which, until recent times, was rarely approached. Neuroendocrine mechanisms within the limbic core of the brain prevent starvation (ventromedial hypothalamus), heighten reward (ventral tegmental area and nucleus accumbens), and attenuate stress (amygdala), in order to promote food-seeking and ingestive behavior and to conserve energy output. In a stressful modern environment with ready access to calorie-dense, highly palatable foods and limited venues for activity, normal, reflexive responsiveness to these three drives makes weight gain all but inevitable. The obesity that ensues often engenders insulin resistance, which undermines the ability of normal hunger and satiety signals to accurately modulate energy intake versus expenditure. Obesity interventions that rely on cognitive information alone cannot free children from this "limbic triangle." Integrated multidisciplinary family- and community-based education, effective stress reduction, and a societal commitment to alter the food and built environments are all necessary components to battle the global obesity epidemic. PMID- 17845136 TI - Tissue factor and factor VIIa as therapeutic targets in disorders of hemostasis. AB - For hemophilia patients with inhibitors against FVIII or FIX, the development of recombinant factor VIIa (rFVIIa) raises the possibility of a therapeutic alternative whose availability and convenience of treatment are comparable to those of FVIII or FIX. In support of this new concept for the treatment of bleeding episodes, pharmacological doses of FVIIa have been shown to induce hemostasis. Pharmacological doses of rFVIIa enhance thrombin generation on thrombin-activated platelets, thereby facilitating the formation of strong, well structured fibrin plugs resistant to premature proteolysis. Modified rFVIIa molecules with a stronger hemostatic potential have been produced. Inhibition of the FVII-TF-dependent pathway (TFPI and rFVIIai) has been tried in attempts to prevent thrombosis, with promising results in animal models so far not confirmed in clinical trials. PMID- 17845137 TI - Therapy of Marfan syndrome. AB - Marfan syndrome is a common inherited disorder of connective tissue caused by deficiency of the matrix protein fibrillin-1. Effective surgical therapy for the most life-threatening manifestation, aortic root aneurysm, has led to a nearly normal lifespan for affected individuals who are appropriately recognized and treated. Traditional medical therapies, such as beta-adrenergic receptor blockade, are used to slow pathologic aortic growth and decrease the risk of aortic dissection by decreasing hemodynamic stress. New insights regarding the pathogenesis of Marfan syndrome have developed from investigation of murine models of this disorder. Fibrillin-1 deficiency is associated with excess signaling by transforming growth factor beta (TGFbeta). TGFbeta antagonists have shown great success in improving or preventing several manifestations of Marfan syndrome in these mice, including aortic aneurysm. These results highlight the potential for development of targeted therapies based on discovery of disease genes and interrogation of pathogenesis in murine models. PMID- 17845138 TI - Hide-and-seek: the challenge of viral persistence in HIV-1 infection. AB - The success of highly active antiretroviral therapy (HAART) for HIV-1 infection has sparked interest in mechanisms by which the virus can persist despite effectively suppressive therapy. Latent HIV-1 reservoirs established early during infection not only prevent sterilizing immunity but also represent a major obstacle to virus eradication. When HIV-1 gains a foothold in the immunologic memory or in certain inaccessible compartments of the human body, it cannot be easily purged by HAART and is able to replenish systemic infection on treatment interruption. Because latently infected cells are indistinguishable from uninfected cells, deliberate activation of latent infection combined with intensified HAART seems to be the best strategy to combat latent infection. Initial hypothesis-driven clinical trials did not achieve their ultimate goal, although they provided valuable insight for the design of future eradication protocols. A more detailed understanding of the basic mechanisms underlying the establishment and long-term maintenance of HIV-1 reservoirs will be critical in developing new eradication approaches. PMID- 17845139 TI - The effect of toll-like receptors and toll-like receptor genetics in human disease. AB - Toll-like receptors (TLRs) enable innate immune recognition of endogenous and exogenous prototypic ligands. They also orchestrate innate and adaptive immune response to infection, inflammation, and tissue injury. Given their significance in the immune response, it is not surprising that genetic variations of TLRs can affect their function and by extension affect the response of the organism to environmental stimuli. The genetics of TLRs provides important insights in gene environment interactions in health and disease, and it may enable scientists to assess patients' susceptibility to diseases or predict their response to treatments. PMID- 17845140 TI - The continuing complexities of high-density lipoprotein metabolism in drug discovery and development. AB - The termination of the Phase III clinical trial of Pfizer's CETP inhibitor torcetrapib, Investigation of lipid level management to understand its impact in atherosclerotic events (ILLUMINATE), due to excess mortality in the treatment group raised many questions for those involved in the discovery and development of drugs targeting high-density lipoprotein and of atherosclerosis in general. Although the reasons for the failure of torcetrapib are still not known, some of the consequences for the wider field are already apparent. Several imaging studies with torcetrapib showed no change in the various measures of lesion size, which gave some confidence in the interpretation of such studies. Although the case for raising high-density lipoprotein is strong and widely accepted, there will be a much closer interrogation of drugs targeting new mechanisms that will result in longer development times. In the meantime, existing drugs which modify high-density lipoprotein are being revisited, particularly niacin. This editorial commentary briefly discusses these and related issues from the perspective of 6 months following the termination of ILLUMINATE. PMID- 17845141 TI - Trial design for cancer (cell)-specific anticancer therapies. AB - The last decade has brought a totally new class of systemic anticancer treatment options, the so-called cancer (cell)-specific (CCS) anticancer agents. Until recently, this treatment modality has been referred to as 'targeted therapy' but as all existing systemic anticancer therapies have a clearly defined target, this seems to be a misnomer. Despite impressive results of several CCS drugs, the present set up of drug development is ill suited for CCSs due to the nature of the majority of these compounds. The authors focus on specific aspects of how to design early clinical trials with this new class of anticancer agents with focus on pharmacodynamic behaviour in relation to response, optimal dose and treatment duration. PMID- 17845143 TI - Pharmacologic targets for atrial fibrillation. AB - Despite advances in treatment, atrial fibrillation (AF) remains the most common arrhythmia in humans. Antiarrhythmic drug therapy continues to be a cornerstone of AF treatment, even in light of emerging non-pharmacologic therapies. Conventional antiarrhythmic drugs target cardiac ion channels and are often associated with modest AF suppression and the risk of ventricular proarrhythmia. Ongoing drug development has focused on targeting atrial-specific ion channels as well as novel non-ionic targets. Targeting non-ionic mechanisms may also provide new drugs directed towards the underlying mechanisms responsible for AF and possibly greater antiarrhythmic potency. Agents that act against these new targets may offer improved safety and efficacy in AF treatment. PMID- 17845142 TI - Endothelial function, arterial stiffness and lipid lowering drugs. AB - The endothelium is a dynamic organ that plays a pivotal role in cardiovascular homeostasis. Alteration in endothelial function precedes the development of atherosclerosis and contributes to its initiation, perpetuation and clinical manifestations. It has been suggested that the assessment of endothelial function could represent a barometer of vascular health that could be used to gauge cardiovascular risk. This review summarises the various methods used to assess endothelium-dependent vasodilatation and their potential prognostic implications. In addition, the techniques used to evaluate arterial stiffness are discussed. The latter is to some extent controlled by the endothelium and has been the subject of considerable research in recent years. This paper also discusses the effects of lipid lowering treatment on both endothelial function and arterial stiffness. PMID- 17845144 TI - Novel migraine therapy with calcitonin gene-regulated peptide receptor antagonists. AB - Primary headaches, for example, migraine and cluster headaches represent the most prevalent neurological disorders, affecting up to 15-20% of the adult population. There is a clear association between head pain and the release of calcitonin gene related peptide (CGRP). In this review the role of CGRP in human cranial circulation is described and the role for specific CGRP antagonism elucidated. It is well known that triptans (5-HT(1B/1D) agonist) alleviate headache in part through normalisation of CGRP levels. The central role of CGRP in migraine pathophysiology has resulted in the development of small-molecule CGRP antagonists with no cardiovascular side effects. Such compounds have high selectivity for human CGRP receptors and are efficacious in the relief of acute migraine attacks. Research indicates that they effect the abluminal side of the blood-brain barrier and that they are not vasoconstrictive, providing a new dimension in therapy. PMID- 17845145 TI - Schizophrenia endophenotypes as treatment targets. AB - Schizophrenia is a complex disorder that encompasses several clinical symptom domains and functional impairments. Existing treatments are meager, effective only against positive symptoms without benefiting negative symptoms and functional impairments. The drug discovery process has focused mostly on targeting D2 dopamine receptors. This followed the serendipitous discovery of the antipsychotic effects of chlorpromazine in the 1950s and, more recently, clozapine. There is a need to identify novel mechanisms in order to discover novel drugs that are effective against each of the symptom clusters and functional impairments associated with the illness. Neurophysiological studies in schizophrenia over the past 3 decades have identified several brain deficits that are stable, using valid animal models that are related to the etiology of the disorder. Many of these deficits are distinct and heritable; these are called endophenotypes. Many have well-characterized neurobiology and may therefore provide molecular targets for drug development. In addition, these endophenotypes help reduce the heterogeneity by identifying homogeneous subgroups of patients with similar pathophysiology, symptoms and functional deficits. Clinical trials of drugs, whose development is based on an endophenotype, will have enhanced statistical power when the trial is carried out in an appropriate cohort of subjects using outcome measures related to the corresponding endophenotype. Furthermore, genes that are associated with these endophenotypes are beginning to be identified. These findings will identify novel molecular targets for drug development with treatment implications for clinical symptom complex and functional deficits marked by the endophenotype. As endophenotypes are present during childhood and adolescence, novel drugs that are developed on the basis of this subgroup could have implications for preventive strategies in schizophrenia. PMID- 17845146 TI - Regulation of angiogenesis and vascular permeability by Src family kinases: opportunities for therapeutic treatment of solid tumors. AB - Aberrant expression or activation of protein tyrosine kinases, including Src and related Src family kinases, is a common occurrence in many human cancers, resulting in deregulation of expression of numerous mediators of cellular functions, including pro-angiogenic molecules. In addition, Src activation regulates vascular permeability of endothelial cells. How these processes contribute to tumor progression and metastasis are the subjects of this review. As Src-selective inhibitors have entered clinical trials for a number of solid tumors, further understanding of the roles of Src kinases in mediating tumor angiogenesis as well as modulating tumor/microenvironment interactions will provide insights into the best use of these inhibitors in treating patients afflicted with tumors in which Src is activated. PMID- 17845147 TI - Targeting tumour-associated macrophages. AB - Clinical and experimental evidence have highlighted that a major leukocyte population present in tumours, the so-called tumour-associated macrophages (TAM), is the principal component of the leukocyte infiltrate supporting tumour growth. Over the years the mechanisms supporting the protumoural functions of TAM have become increasingly clear and in several experimental tumour models, the activation of an inflammatory response (most frequently mediated by macrophages) has been shown to play an essential role for full neoplastic transformation and progression. This evidence strongly supports the idea that TAM are central orchestrators of the inflammatory networks expressed in the tumour microenvironment, and suggest these cells as possible targets of anticancer therapies. PMID- 17845148 TI - Present and future therapeutic strategies in non-alcoholic fatty liver disease. AB - Non-alcoholic fatty liver disease (NAFLD) is found in individuals who do not drink or abuse alcohol and represents a significant health burden for the general community. NAFLD is often associated with one or more features of the metabolic syndrome and has potential for evolution towards non-alcoholic steatohepatitis (NASH), the necro-inflammatory form of liver steatosis. The most worrisome evolutive events in a subgroup of NASH patients include advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. Pathophysiology of NAFLD/NASH is complex, but studies point to a pre-eminent role of oxidative stress and lipid peroxidation in the liver, including early mitochondrial dysfunction. Changes follow an insulin resistance status with a background of a chronic pro inflammatory status due to an excess of visceral adiposity. Although no established therapy exists for NAFLD/NASH, potential therapeutic approaches are discussed in this review. PMID- 17845149 TI - British Pharmacology Society 2nd Focused meeting on Cell Signalling: GPCRs have sunny days in springtime Leicester. AB - The British Pharmacology Society recently held its 2nd Focused meeting on Cell Signalling in April 2007 at which a number of leading investigators from throughout the world presented findings that emphasized cellular and molecular aspects of G-protein-coupled receptor (GPCR) biology. Although the presentations highlighted both in vitro and in vivo studies, there was renewed and increased attention paid to systems with physiological (or near-physiological) levels of receptor expression. Mechanisms involved in regulating receptor expression, receptor recognition and activation by different classes of drugs, and in the interaction of G-protein-coupled receptor with other molecular entities, including heterotrimeric G proteins, were major themes of the presentations. Several speakers emphasized the challenges of drug discovery in relation to G protein-coupled receptor, as well as their continuing importance in pharmacology and therapeutics. PMID- 17845150 TI - Bronchiolitis obliterans: a rare chronic pulmonary complication associated with Stevens-Johnson syndrome. AB - Pulmonary manifestations are well recognized during the acute phase of Stevens Johnson syndrome but persistent pulmonary sequela is rarely reported. We report two boys with bronchiolitis obliterans following the acute phase of Stevens Johnson syndrome and discuss the clinical picture and treatment of persistent pulmonary complications with reference to earlier reports. PMID- 17845151 TI - Cranial fasciitis in an 8-year-old boy: clinical and histopathologic features. AB - Cranial fasciitis is an uncommon benign disorder characterized by a fibroblast like cell proliferation, observed almost exclusively in children. Clinically, it manifests as a rapidly growing, solitary nodule in the head or neck area. Underlying bone involvement (cranial cortical erosion) is frequently detected. Histopathologic analysis allows differentiation between cranial fasciitis and fibrohistiocytic or even sarcomatous lesions observed in children. Cranial fasciitis is considered to be a reactive, non-neoplastic disorder and is usually cured by a simple excision. An increased awareness of the clinical and histopathologic characteristics of this entity seems important to establish the diagnosis, to adopt an adequate, conservative treatment and to avoid unnecessarily aggressive procedures. PMID- 17845152 TI - Focal epithelial hyperplasia (Heck disease) in a black child. AB - We describe a 3-year-old African male child with focal epithelial hyperplasia (Heck disease). The clinical diagnosis was confirmed histologically and by the finding of human papillomavirus type 32. PMID- 17845153 TI - Hair coil strangulation--an uncommon cause of penile edema. AB - Penile strangulation by hair coil is an uncommon, under-recognized condition with a spectrum of potential complications including urethral transection and partial or complete penile amputation. Early recognition and treatment can greatly reduce the incidence of these devastating complications. We report a 5-year-old, circumcised boy with penile edema and erosions secondary to a hair wrapped around the coronal sulcus. Prompt diagnosis and removal of the hair led to rapid resolution without surgical repair. We also analyze the possible underlying causes which can lead to strangulation of the penis with a hair. PMID- 17845154 TI - Placental anomalies in children with infantile hemangioma. AB - Evaluation of the placenta provides some important insights into pathophysiologic changes that take place during the prenatal and intrapartum process. We investigated the pathogenic significance of placental features and their relationship to the development of infantile hemangioma in order to obtain a better understanding of its cause. Placental specimens were reviewed from 26 singleton pregnancies of women whose offspring weighed less than 1500 g. A group of 13 neonates who developed infantile hemangioma in the immediate neonate period were compared with 13 healthy preterm infants of comparable postconception age who had no infantile hemangioma. Pathologic placental changes were analyzed in both groups. Gross lesions with disturbance of the utero-placental circulation were found in all placentas from children who developed infantile hemangioma, including massive retroplacental hematoma in two infants, extensive ischemic infarction in seven, and large dilatated vascular communications, severe vasculitis, chorioamnionitis and funiculitis in four. Placental features included percentages greater than 25% of avascular villi, platelet and fibrin aggregates, and multifocal disease involving more than one histologic section. Examination of 13 placentas of low-birth-weight infants without infantile hemangioma only showed abnormal placentation in one and isolated villous dismaturity in two. The higher ratio of placental pathologic findings in patients with infantile hemangioma suggests that reduced placental oxygen diffusive conductance contributes to fetal hypoxic stress and that hypoxic/ischemic changes in the placenta could be related to infantile hemangioma development via vascular endothelial growth factor and placental growth factor expression, among others, within the villious vessels and throphoblasts. PMID- 17845155 TI - Reticular infantile hemangioma of the limb can be associated with ventral-caudal anomalies, refractory ulceration, and cardiac overload. AB - We describe six patients with an uncommon variant of infantile hemangioma that we have termed reticular, occurring in the extremity, which were associated with intractable ulceration, anogenito-urinary-sacral anomalies, and sometimes cardiac overload. The extreme end of the spectrum is exemplified by a male neonate who presented with a stained, enlarged, pulsatile lower extremity, and cardiac failure. He also had hepatic hemangiomas and ambiguous genitalia. Progressive soft tissue necrosis and bony destruction necessitated amputation. The histopathologic features differed from those of typical infantile hemangioma: infiltrative (not lobular) and involving fascia, muscle, and bone. The mid spectrum is illustrated by five females with reticular infantile hemangioma of the lower limb, buttock, and perineum. Four of these infants had a ventral-caudal anomaly, including omphalocele, recto-vaginal fistula, solitary/duplex kidney, imperforate anus, and tethered cord; one infant also had hepatic hemangiomas. Deep ulcerations healed following corticosteroid therapy; one patient required skin graft for closure of a thigh wound. The minor end of the spectrum is exemplified a patchy lesion in the distal limb. The reticular variant of infantile hemangioma can be confused with other vascular anomalies in the limb, such as capillary malformation, cutis marmorata telangiectasia congenita, diffuse arteriovenous malformation (Parkes Weber syndrome) and capillary-lymphatico venous malformation (Klippel-Trenaunay syndrome). The macular network-like appearance of the tumor and coexisting ventral-caudal structural anomalies is analogous to the association of posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities association in the craniofacial region. PMID- 17845156 TI - The influence of atopic status and potential risk factors for sensitization on histamine skin reactivity in unselected Belgian children. AB - The histamine skin response is widely used as a standardized positive control in the performance of skin prick testing. As a part of the Aalst Allergy Study, we investigated whether histamine skin reactivity, using histamine 10 mg/mL, was influenced by age, gender, ethnic origin, environmental exposure, specific sensitization patterns, or other factors. The parents of 2021 nonselected children aged 3.4-14.8 years completed a baseline questionnaire and gave written informed consent for skin prick testing with seven common aeroallergens on their child. Sensitized children had significantly larger histamine wheal sizes than nonsensitized children (mean 4.3 vs 4.0 mm, p < 0.05). A significant difference was found in histamine wheal size between nonsensitized versus multiply sensitized children (p < 0.001), but not between mono-sensitized versus multiply sensitized children (p = 0.105). The only other factors associated with significantly larger histamine wheal sizes were a history of eczema and a history suggestive for asthma on the Brief Pediatric Asthma Screen Plus. The histamine wheal was absent in 8.9% of children. In conclusion, sensitization and some other clinical indicators of atopy were associated with a larger histamine skin wheal. Other conditions including gender and environmental exposure did not have an influence on histamine skin reactivity, which strengthens the use of histamine as a reference in skin prick testing in this age group. PMID- 17845157 TI - Sporotrichosis in childhood: clinical and therapeutic experience in 25 patients. AB - Sporotrichosis in an uncommon mycoses in childhood and is generally associated with injuries received as a consequence of farm work. We undertook a retrospective study of sporotrichosis in children and adolescents seen over a 10 year period, focusing on their clinical, epidemiologic, and mycologic features as well as treatment. We included 25 children with a mean age of 9.3 years. Most of those affected were schoolchildren (84%) from rural areas. The main clinical variety of sporotrichosis seen was the lymphocutaneous form (64%), followed by the fixed cutaneous form (36%), and one instance of the disseminated cutaneous form. Most lesions were located on the upper limbs (40%) and the face (36%). Sporothrix schenckii was isolated in all patients and 24 of 25 had a positive sporotrichin skin test. Nineteen patients were treated and cured clinically and mycologically with potassium iodide, three were cured with itraconazole and one with heat therapy. PMID- 17845158 TI - Serum estradiol levels in infants with and without labial adhesions: the role of estrogen in the etiology and treatment. AB - No strong evidence has been found that estrogen levels in girls with labial adhesions are lower than in girls without. Therefore, this study was based on the determination of estradiol levels in girls with and without labial adhesions in order to show whether a considerable difference exists between these two groups. Serum estradiol levels were measured in 59 infants with labial adhesions and in 60 healthy infants. No significant age difference was seen between affected infants and controls, with a mean age of 12.7 and 12.4 months, respectively. Serum estradiol levels ranged from 6.5 to 14.3 pg/ml (10.27 +/- 1.897) in those with labial adhesions and from 6.4 to 15.1 pg/ml (10.47 +/- 2.006) in controls, a statistically insignificant difference (p = 0.5764). When taking into consideration the effect of estrogen on wound healing and the fact that the difference in estrogen levels between the infants with and without labial adhesion is not significant, it is concluded that hypoestrogenism does not take place in the development of labial adhesions, but that creams containing estrogen might have a beneficial effect on healing after mechanical separation of the adhesion by enhancing wound reepithelialization. PMID- 17845159 TI - Port-wine-stain-associated dermatitis: implications for cutaneous vascular laser therapy. AB - Port-wine stains are congenital vascular malformations affecting 0.3% to 0.5% of infants. Dermatitis occurring exclusively or most severely within port-wine stains has been described in the literature. Traditionally, topical corticosteroid therapy has been used for the treatment of dermatitis, while pulseddye laser treatment is considered a safe and effective means of lightening the appearance of congenital port-wine stains. To describe the development of port-wine stain-associated dermatitis as well as a rational treatment approach to these patients, we studied three children with facial, limb, or truncal port-wine stains who developed dermatitis within the congenital vascular malformation either prior to or during treatment with pulseddye laser. Laser therapy of dermatitis-affected areas was subsequently deferred pending resolution of the dermatitis with topical corticosteroid or topical calcineurin inhibitor treatment. While pulseddye laser therapy is an effective means of lightening port wine stains and achieving lasting resolution of any associated dermatitis, this therapy to dermatitis-affected areas should be postponed until the inflammation resolves to minimize the risk of laser-associated adverse effects. PMID- 17845160 TI - Congenital curved nail of the fourth toe--three different clinical presentations. AB - A congenital curved nail of the fourth toe (NIM 219070) is a rare nail deformity with no other associated abnormalities. Three patients with this congenital anomaly are reported here. Radiologic examination in all three revealed distal symphalangism of the fourth toes bilaterally. The clinical manifestations in these patients included white discoloration of the proximal nails and hyperkeratotic tylosis. PMID- 17845161 TI - Evaluation of a congenital erosive and vesicular dermatosis healing with reticulated supple scarring. AB - Congenital erosive and vesicular dermatosis healing with reticulated supple scarring is a rare disease first reported by Cohen et al in 1985. To date only 13 cases of this disease have been reported. This entity is characterized by the presence of erosions and vesicles at birth, usually affecting about 75% of the body which heals with reticulated scarring in weeks to months. We report a case of this disease related to a boy who was born with erosions affecting his head, trunk, and limbs. All lesions healed completely after 3 months with reticulated scarring without any clinical complications. PMID- 17845162 TI - Focal dermal hypoplasia with unusual cutaneous features. AB - Focal dermal hypoplasia (Goltz syndrome) is a rare genetic condition characterized by numerous malformations in different organ systems derived from the ectoderm and mesoderm. We present an infant with focal dermal hypoplasia who, besides having a constellation of anomalies commonly encountered in patients with this syndrome, manifested additional unusual features such as an early inflammatory vesicular stage and a cleft lip and palate. We emphasize that a prompt, well-orchestrated and effective multidisciplinary intervention can help improve the quality of life in patients afflicted with this condition. PMID- 17845163 TI - Persistent linear bands in infancy acquired after local pressure: a consequence of mast cell activation? AB - A 10-month-old girl with marked symptomatic dermographism presented with linear bands at the sock line noted to have developed following an episode of localized urticaria and angioedema at the sock line. We speculate that release of mast cell mediators associated with the dermographism may have triggered the development of the linear bands. PMID- 17845164 TI - Acrodermatitis enteropathica-like dermatosis associated with ornithine transcarbamylase deficiency. AB - The urea cycle is the major metabolic pathway for excretion of waste nitrogen. Ornithine transcarbamylase deficiency is the most frequent urea cycle disorder. It is a hereditary-X-linked disease with over 150 mutations described. Ornithine transcarbamylase deficiency causes vomiting, lethargy, hyperventilation, and even death, mainly in the neonatal period. Ammonia, an extremely toxic molecule for the organism, is generated during protein catabolism and is accumulated in patients with this deficiency. Part of the treatment consists of a low-protein diet, to avoid hyperammonemia episodes, which can even have a fatal outcome. Patients can become deficient in several amino acids, either through the low protein diet or directly through the primary enzyme deficiency; this in turn can cause an acrodermatitis enteropathica-like dermatosis. PMID- 17845165 TI - Angioblastoma showing aggravation after treatment with long-pulsed Nd:YAG laser (1064 nm). AB - Angioblastoma usually develops in infancy or early childhood on the neck or upper trunk. It is known to be slowly progressive and benign in nature, but treatment guidelines have not yet been established. Spontaneous regression has been occasionally documented, and treatment with pulsed dye laser, excision, high-dose steroids, and interferon alpha have been successful in individual patients. Our patient experienced partial response to interferon alpha injection, and for further treatment, long-pulsed Nd:YAG laser (1064 nm) treatment was performed. However, unexpectedly, the tumor was rapidly aggravated. We report this occurrence to increase awareness of trauma-induced aggravation phenomena in angioblastoma. PMID- 17845166 TI - Childhood pustular psoriasis associated with Panton-Valentine leukocidin producing Staphylococcus aureus. AB - We report the association of a generalized pustular psoriasis and infection by Staphylococcus aureus which produced Panton-Valentine leukocidin in a 5-year-old child. Another S. aureus strain with the same toxin gene content was also isolated among three family members presenting with cutaneous lesions. Although a methicillin-resistant staphylococcal strain has been reported in association with pustular psoriasis, this is the first report of a Panton-Valentine leukocidin strain associated with generalized pustular psoriasis. The causal relationship between S. aureus produced Panton-Valentine leukocidin and skin lesions is discussed. PMID- 17845167 TI - A randomized, investigator-blinded, time-ranging study of the comparative efficacy of 0.5% malathion gel versus Ovide Lotion (0.5% malathion) or Nix Creme Rinse (1% permethrin) used as labeled, for the treatment of head lice. AB - One hundred seventy-two subjects with head lice participated in a five-way, investigator-blinded, parallel-group, active-controlled study comparing 0.5% malathion gel (30, 60, and 90 minutes applications), Ovide Lotion (0.5% malathion), and Nix Creme Rinse (1% permethrin). All subjects were treated on day 1. Participants were reevaluated at day 8 +/- 1 and those with live lice were retreated with the same product, for the same duration as day 1. Cure, defined as the absence of live lice, was evaluated 14 +/- 2 days after the last treatment and 161 subjects completed the study according to the protocol. Compared to Nix, treatment success rates were statistically superior for all malathion gel and Ovide groups. Retreatment rate for Nix was 70%, which was statistically more than the malathion groups. The highest treatment success rates were observed for the 30-minute malathion gel (98% intent-to-treat and 100% per-protocol [PP]) and the 8 to 12 hour Ovide application (97% intent-to-treat and 100% PP). In conclusion, the 30-minute malathion gel, which contains the same ingredients and concentrations as Ovide, provides comparable efficacy, offers increased safety and is more cosmetically acceptable than Ovide. PMID- 17845168 TI - Follicular keratosis of the chin treated with 1.24R-dihydroxyvitamin D3 ointment. AB - In follicular keratosis of the chin, keratotic follicular papules occur on the chin and jaw due to localized prolonged pressure and friction on the naked skin. We present one patient with this disorder. The dermatoscopic examination revealed many well-demarcated yellow spindle bodies in the patchy lesion. Therapy with 1.24R-dihydroxyvitamin D3 ointment was effective during the treatment but had no residual positive effect. PMID- 17845169 TI - Treating pediculosis--those nit-picking details. PMID- 17845170 TI - Multiple keratotic papules and skeletal anomalies. PMID- 17845171 TI - Pustules on the nose of an 11-year-old girl. PMID- 17845173 TI - Distraction anesthesia for pediatric dermatology procedures. PMID- 17845172 TI - A child with multiple petechiae and eczematous plaques. PMID- 17845174 TI - What syndrome is this? Brachmann de Lange syndrome. PMID- 17845175 TI - Treatment of pseudoxanthoma elasticum with tocopherol acetate and ascorbic acid. AB - Pseudoxanthoma elasticum is an inherited systemic disorder of connective tissue characterized by fragmentation of elastic fibers and calcification in cutaneous, ocular, and cardiovascular systems. Mutation in the ATP-binding cassette subfamily C member 6 gene has recently been found in people with pseudoxanthoma elasticum. However, the precise mechanisms of elastic fiber fragmentation and calcification remain obscure. Recently, it has been reported that mild chronic oxidative stress affects pseudoxanthoma elasticum fibroblasts. This suggests that reactive oxygen scavengers might improve this disorder. PMID- 17845176 TI - Isotretinoin-induced agranulocytosis. AB - Isotretinoin is used to treat a spectrum of dermatologic conditions. The present article reports the case of a 15-year-old female patient who exhibited agranulocytosis after the initiation of isotretinoin administration. Agranulocytosis is a rare but life-threatening side effect of isotretinoin use, and clinicians must be aware of agranulocytosis. PMID- 17845177 TI - Dermatologic features in Pallister-Killian syndrome and their importance to the diagnosis. PMID- 17845178 TI - Nevus sebaceous syndrome with facial hemihypertrophy. AB - Nevus sebaceous syndrome is a member of the epidermal nevus syndromes group, and is characterized by extensive nevus sebaceous, seizures, and mental retardation. We present an affected 5-month-old boy who had facial hemi-hypertrophy and recurrent seizures. PMID- 17845179 TI - Chronic varicella-zoster skin infection complicating the congenital varicella syndrome. AB - Congenital varicella is a rare syndrome arising when a pregnant woman develops varicella before the 24th week of pregnancy. We report an occurrence of congenital varicella syndrome complicated by a chronic varicella zoster virus skin infection in an immunocompetent infant. The chronic verrucous skin infection is puzzling in our patient, as this disease is usually described in immunosuppressed patients. PMID- 17845180 TI - Stevens-Johnson syndrome associated with brucella infection. AB - Stevens-Johnson syndrome is a potentially fatal condition that manifests mainly on the skin and mucosal surfaces but also affects other vital organs. There are no report of Stevens-Johnson syndrome caused by brucella infection in the literature. In this article, a previously healthy boy, diagnosed as Stevens Johnson syndrome associated with brucella infection, is reported. PMID- 17845181 TI - ''Ectopic eyelashes'' (ectopic cilia) in a 2-year-old girl: brief report and discussion of possible embryologic origin. AB - Cilia, or eyelashes, are unique hair follicles normally found at the eyelid margin. The spectrum of cilial anomalies includes cilial row duplication, agenesis, and ectopic placement. Ectopic cilia are the most rare of cilial anomalies. We report a case of a 2-and-a-half-year-old girl with ectopic cilia of the anterior tarsal plate, an extremely rare, congenital anomaly that is most often not associated with other findings and likely results from an event during embryogenesis. PMID- 17845182 TI - Subcutaneous fat necrosis of the newborn and lactic acidosis. AB - Subcutaneous fat necrosis of the newborn (SFN) is an uncommon, self-limited condition of neonates and infants. However, hypercalcemia may be a potentially life-threatening complication of the otherwise self-healing process. Rare complications such as thrombocytopenia, hypertriglyceridemia, hypoglycemia, calcium deposits in the liver, inferior vena cava, atrial septum of the heart, and nephrocalcinosis have been reported. To our knowledge, this is the first description of a patient in whom lactic acidosis was encountered in an infant along with the other known complications of SFN. PMID- 17845183 TI - Uncombable hair syndrome. AB - A 4-year-old boy was noted to have unruly, spangled hair, which could not be combed flat. His mother reported that his hair had always had that texture and that it seemed to grow slowly. A hair pull test demonstrated that hairs could not be easily extracted, and light microscopic examination of the hair revealed pathognomonic characteristics of uncombable hair syndrome, including a triangular cross-sectional shape and canal-like longitudinal depressions. PMID- 17845184 TI - Giant flank hematoma in a neonate. PMID- 17845185 TI - Linear connective tissue nevus. AB - Multiple connective tissue nevi in linear arrangements, which was previously described as zosteriform connective tissue nevus, is a rare variant of connective tissue nevus. We herein report the case of an 8-year-old Japanese boy with this disease. He developed a small mass on the upper region of his right inner ankle at the age of one-half years. Then, other lesions had appeared on the inner side of his right lower leg, thigh, and groin within the next 2 years. Furthermore, multiple new lesions in linear arrangements had appeared on the right half of the abdomen and on the extensor side of the right forearm at the age of 8 years. A biopsy specimen revealed abnormalities in both the collagen bundles and the elastic fibers. Since the distribution was along Blaschko's lines, not dermatomes, we propose that the diagnosis "linear connective tissue nevus" is suitable for this clinical study. PMID- 17845186 TI - Fucosidosis: a therapeutic challenge. PMID- 17845187 TI - Premature sebaceous hyperplasia in a neonate. PMID- 17845188 TI - Facial eruption of viral warts in a child treated with 0.03% tacrolimus ointment for atopic dermatitis. PMID- 17845189 TI - Linear epidermolytic verrucous epidermal nevus of the male genitalia. PMID- 17845190 TI - Type 2 segmental trichoepitheliomatosis: a genetic concept that may explain congenital multiple trichoepitheliomas in the lines of Blaschko. PMID- 17845191 TI - Chemical burn: a risk with outdated povidone iodine. PMID- 17845192 TI - Atypical fibroxanthoma in a child without xeroderma pigmentosum. PMID- 17845193 TI - Mucoepidermoid carcinoma on the scalp of a child. PMID- 17845194 TI - Lichen planus appearing subsequent to generalized lichen nitidus in a child. PMID- 17845195 TI - Methylmalonic acidemia presenting with an ichthyosis vulgaris-like aspect. PMID- 17845196 TI - Epidermodysplasia verruciformis-like disorder in a teenager with HIV and HCV infections. PMID- 17845197 TI - Extensive sebaceous/epidermal nevus associated with cardiac arrhythmia. PMID- 17845198 TI - Kikuchi disease with transient eruption in a 7-year-old boy. PMID- 17845199 TI - Congenital mastocytosis associated with neurosensory deafness. PMID- 17845200 TI - CD57+ cells and recurrent spontaneous abortion. PMID- 17845202 TI - Elevated Th1/Th2 cell ratios in a pregnant woman with a history of RSA, secondary Sjogren's syndrome and rheumatoid arthritis complicated with one fetal demise of twin pregnancy. AB - PROBLEM: Elevated Th1/Th2 cytokine producing CD3(+)/CD4(+) cell ratios were reported in women with a history of recurrent spontaneous abortion (RSA) and multiple implantation failures. We report, significantly elevated Th1/Th2 cell ratios were noticed in a pregnant woman with twin pregnancies complicated with one fetal demise, who had a history of RSA, secondary Sjogren's syndrome (SS), and rheumatoid arthritis. METHOD OF STUDY: Case report. RESULTS: Peripheral blood Th1/Th2 cell ratios were significantly elevated 3 weeks prior to a fetal demise of twin pregnancies at 20 week gestation. Two weeks after fetal demise, the ratio of intracellular tumor necrosis factor-alpha/interleukin-10 producing CD3(+)/CD4(+) cells in peripheral blood was further increased to three times higher than prior ratio. Elevated Th1/Th2 ratio was down regulated after increasing dose of IVIg treatment. The patient gave birth to a male baby weighing 2650 g at 36 weeks gestation. No serious complications were found in the patient or the baby. CONCLUSION: Systemic inflammatory immune response pre-exists prior to a fetal demise and the degree of inflammatory immune response got worse with a presence of fetal demise in utero. We infer that the placenta is not an immunological barrier to maternal Th1/Th2 immune responses. PMID- 17845201 TI - Activation of T cells by cross-linking Qa-2, the ped gene product, requires Fyn. AB - PROBLEM: Qa-2, the product of the Ped (preimplantation development) gene, regulates the rate of cell division of preimplantation mouse embryos by an unknown mechanism. Due to the limited availability of preimplantation embryos, T cells were used as a model system to assess the possible roles of Fyn and Lck, and two downstream effectors, PI-3 kinase and Akt, in Qa-2 induced cell proliferation. METHOD OF STUDY: Resting T cells were stimulated to proliferate by treating with mouse anti-Qa-2 antibody, cross-linking with anti-mouse immunoglobulin, and adding PMA. The effects of kinase inhibitors on this proliferation were studied. Co-immunoprecipitates of T-cell lysates were analyzed for possible associations between Qa-2 and Fyn or Lck. Fyn knockout mice (Fyn-/-) were used to determine whether Fyn is required for T-cell activation induced by cross-linking Qa-2. RESULTS: An inhibitor of Src family kinases and inhibitors of PI-3 kinase and Akt suppressed proliferation of resting T cells induced by cross linking Qa-2. Fyn, but not Lck, co-immunoprecipitated with Qa-2. Fyn-/- T cells failed to proliferate in response to Qa-2 cross-linking. CONCLUSION: Fyn, PI-3 kinase, and Akt are required for the activation of T cells by cross-linking Qa-2. PMID- 17845203 TI - Gene expression profiling of the rat endometriosis model. AB - PROBLEM: To investigate the molecular mechanism of endometriosis, gene expression profiling was analyzed in a rat endometriosis model. METHOD OF STUDY: An endometriosis model was induced by uterine autotransplantation in the peritoneal cavity on a female-SD rat (8 weeks old). As control samples, the normal uterine tissues were used. The gene expression was compared between endometriotic lesions and normal uterine tissues by cDNA microarray analysis, quantitative real time RT PCR and immunohistochemistry. RESULTS: The expression of 71 genes was upregulated and that of 45 genes was downregulated in the endometriotic lesions compared to normal uterine tissues. The upregulated genes included genes encoding cytokines, chemokines, growth factors and cell adhesion molecules. The levels of transcripts of osteopontin, Lyn, Vav1, Runx1, and l-selectin in the endometriotic lesions were 130, 10, 10, 12 and 46-fold higher than the respective levels in the eutopic endometrial samples. CONCLUSION: The results suggest that osteopontin, Lyn, Vav1, Runx1, and l-selectin play important roles in the pathogenesis of endometriosis. PMID- 17845204 TI - Value of combined clinical information and thyroid peroxidase antibodies in pregnancy for the prediction of postpartum thyroid dysfunction. AB - PROBLEM: To investigate the utility of thyroid peroxidase antibodies (TPOAb) in early pregnancy combined with clinical information for prediction of postpartum thyroid dysfunction (PPTD) within 1 year postpartum. METHOD OF STUDY: We studied 98 pregnant women by determining their TPOAb levels in early pregnancy, as well as their serum thyrotropin and free thyroid (fT4) levels at 6 and 12 months postpartum. Furthermore, they answered a questionnaire and physical examination was performed by only one examiner. RESULTS: Of the 98 women, 10 were positive TPOAb in early pregnancy. The overall risk of PPTD within 1 year of follow-up was 10.2% (95% CI 4.1-16.3). Risk of PPTD was significantly higher among women with a family history of thyroid disease, TPOAb positive and presenting goiter in early pregnancy. The sensitivity, specificity and positive predictive value of TPOAb in PPTD prediction were 60.0%, 95.5% and 60%. Restricting screening to women with a family history of thyroid disease or presenting goiter increases the positive predictive value from 60% to 82.4%. CONCLUSION: Our results suggest that TPOAb could be used as a screening test for PPTD prediction at least among women who present a high risk of developing PPTD. PMID- 17845205 TI - Uterine cervical inflammatory cytokines, interleukin-6 and -8, as predictors of miscarriage in recurrent cases. AB - PROBLEM: Inflammatory changes frequently occur in cases of second trimester miscarriage or pre-term delivery, but little attention has been paid to this association with recurrent miscarriage. As interleukin-6 and interleukin-8 are inflammatory cytokines reported to be associated with bacterial vaginosis, intrauterine infections, and pre-term delivery, we here investigated whether they might have predictive value for spontaneous abortion in recurrent cases. METHOD OF STUDY: Cervical mucus and sera were collected at 4-5 weeks' gestation from a total of 59 patients with a history of two or more unexplained consecutive first trimester miscarriages, and examined by enzyme-linked immunosorbent assay. Patients then were followed up without medication and their pregnancy outcomes were compared with the test results. RESULTS: Of a total of 59 patients, 13 (22%) miscarried subsequently. Both IL-6 and IL-8 in cervical mucus were significantly higher in patients who miscarried subsequently than in those who had a live birth. In addition, there was no correlation between cervical mucus and serum concentrations of IL-6 and IL-8 take at the same time, and there was no relation with serum IL-6 and IL-8 levels between the two groups. CONCLUSION: Cervical IL-6 and IL-8 might have predictive value for cases of recurrent miscarriage. PMID- 17845206 TI - RCAS1 decidual immunoreactivity in severe pre-eclampsia: immune cell presence and activity. AB - PROBLEM: Pre-eclampsia seems to be related to the disturbance of immune tolerance regulation during pregnancy. Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) decidual level alterations were concomitant with changes in immune cell number and activity in decidua. As decidual immunomodulating activity participates in the development of immune tolerance during pregnancy, we aimed to evaluate the immunoreactivity level of decidual RCAS1 with respect to the presence and activity of immune cells. METHOD OF STUDY: RCAS1, CD3, CD56, CD69, and CD25 immunoreactivity was assessed by immunohistochemistry in 30 decidual samples derived from patients with severe pre-eclampsia (sPE) and from a healthy control group. RESULTS: RCAS1 immunoreactivity was statistically significantly higher in decidual tissue samples derived from patients with sPE tissue than in those derived from healthy patients in whom elective cesarean section at term was performed. A statistically significantly lower number of CD56(+) and CD3(+) cells and lower immunoreactivity level of CD69 were found in patients with sPE compared with those from the control group. CONCLUSION: The limited immune cells infiltration in decidua during sPE is associated with increase in RCAS1 decidual level. PMID- 17845207 TI - The presence of midkine and its possible implication in human ovarian follicles. AB - PROBLEM: Ovarian follicles undergo a dynamic change to provide a mature ovum, and the process involves angiogenesis, follicular cell proliferation and leukocyte recruitment. Midkine (MK) is a heparin-binding growth factor that has angiogenic, mitogenic, and chemotactic activities. In the present study, we investigated the presence of MK and its possible role in human ovarian follicles. METHOD OF STUDY: Follicular fluid (FF) and luteinized granulosa cells (LGC) were collected from women undergoing in vitro fertilization and embryo transfer. Expression of MK protein in FF was examined by Western blotting. Concentrations of MK, estradiol and oxygen in FF were measured. 5-bromo-2'-deoxyuridine (BrdU) incorporation assay was performed in LGC. Normal ovarian tissues were obtained surgically and used in in-situ hybridization of MK mRNA. RESULTS: The presence of MK protein was verified in FF. MK mRNA was expressed in both granulosa cells and theca cells of large follicles. There is a significant negative correlation between the concentrations of MK and oxygen in FF, and a significant positive correlation between the concentrations of MK and estradiol. MK promoted BrdU uptake in LGC. CONCLUSION: The present findings imply that hypoxic condition, a characteristic of growing follicles, associates with the production of MK. Given that MK is involved in granulosa cell proliferation and estradiol production in developing follicles, MK may play a role as a local regulator in the human ovary. PMID- 17845208 TI - Serum antiendometrial antibodies and diagnosis of endometriosis. AB - PROBLEM: The purpose of the present prospective multi-center study is to investigate the relationship between laparoscopic diagnosis of endometriosis and results of a serum antiendometrial antibody (AEA) assay. METHOD OF STUDY: Indirect immunofluorescence detection of AEA was performed on serum specimens from patients presenting with dysmenorrhea or chronic pelvic pain and infertility (n = 2609) utilizing frozen sections of endometrium acquired on cycle days 18-21 from normally cycling women without endometriosis. Diagnostic laparoscopy was performed within 1 year of AEA assay on 527 tested women. RESULTS: The relationship between the serum AEA and laparoscopic verification was characterized by a positive predictive value = 88%, negative predictive value = 86%, sensitivity = 87% and specificity = 87%. CONCLUSION: The AEA assay is a very good screening test for patients suspected of having endometriosis and should be utilized prior to laparoscopy in diagnostic categories of dysmenorrhea or chronic pelvic pain and infertility. PMID- 17845210 TI - Immunopathogenesis of psoriasis. AB - Psoriasis is a chronic skin disease that affects about 1.5% of the Caucasian population and is characterized by typical macroscopic and microscopic skin alterations. Psoriatic lesions are sharply demarcated, red and slightly raised lesions with silver-whitish scales. The microscopic alterations of psoriatic plaques include an infiltration of immune cells in the dermis and epidermis, a dilatation and an increase in the number of blood vessels in the upper dermis, and a massively thickened epidermis with atypical keratinocyte differentiation. It is considered a fact that the immune system plays an important role in the pathogenesis of psoriasis. Since the early 1990s, it has been assumed that T1 cells play the dominant role in the initiation and maintenance of psoriasis. However, the profound success of anti-tumor necrosis factor-alpha therapy, when compared with T-cell depletion therapies, should provoke us to critically re evaluate the current hypothesis for psoriasis pathogenesis. Recently made discoveries regarding other T-cell populations such as Th17 and regulatory T cells, dendritic cells, macrophages, the keratinocyte signal transduction and novel cytokines including interleukin (IL)-22, IL-23 and IL-20, let us postulate that the pathogenesis of psoriasis consists of distinct subsequent stages, in each of them different cell types playing a dominant role. Our model helps to explain the varied effectiveness of the currently tested immune modulating therapies and may enable the prediction of the success of future therapies. PMID- 17845209 TI - Human leukocyte antigen may predict outcome of primary recurrent spontaneous abortion treated with paternal lymphocyte alloimmunization therapy. AB - PROBLEM: Recurrent spontaneous abortion (RSA) is defined by at least three consecutive abortions in otherwise healthy couples. Paternal lymphocyte alloimmunization therapy (PLAT) is an effective therapy for RSA in some cases, but there are no predictive markers about the effectiveness of PLAT. METHOD OF STUDY: Forty-two consecutive cases with primary RSA treated by PLAT and 23 controls were the subjects. Polymorphisms of human leukocyte antigen (HLA)-E, HLA G, HLA-A, HLA-B, HLA-C and HLA-DRB1 were investigated by sequenced based typing. Promoter polymorphism and a 14 bp ins/del polymorphism in exon 8 were also investigated for HLA-G. RESULTS: Thirty-eight RSA wives became pregnant within 1 year after PLAT. Among them, 27 obtained babies (succeeded PLAT cases), while 11 again aborted with no detectable chromosomal abnormalities in the aborted fetuses (aborted PLAT cases). The frequencies of HLA-G*010401, A*2402, B*5201, and DRB1*1502 were significantly increased in the aborted cases than those in the succeeded cases or controls. Of note, HLA-G*010401 was found in all aborted cases whereas it was found in 51.9% of succeeded cases (odds ratio = 21.4, P = 0.006, P(c) = 0.03), and the presence of HLA-G*010401 could predict the abortion after PLAT with sensitivity and specificity of 100% and 48.1%, respectively. CONCLUSION: Human leukocyte antigen testing may be useful for predicting effectiveness of PLAT in RSA. PMID- 17845211 TI - Agonists of proteinase-activated receptor-2 affect transendothelial migration and apoptosis of human neutrophils. AB - Skin is the first barrier preventing microorganism invasion in host. Wounds destroy this defense barrier and, without an appropriate care, may lead to sepsis. Neutrophil activation and immigration plays an important role at the inflammatory stage of wound healing. Neutrophils are known to express proteinase activated receptors (PARs), which can be activated by serine proteases, also by enzymes involved in wound healing. We previously reported that PAR(2) agonists up regulate cell adhesion molecule expression and cytokine production by human neutrophils. Here, we demonstrate that PAR(2) agonists (serine proteases as well as synthetic peptides) reduce transendothelial migration of neutrophils and prolong their life in vitro. Synthetic PAR(2) agonist also enhanced protective interferon (IFN)gamma-induced FcgammaRI expression at neutrophil cell surface. Of note, IFNgamma is a cytokine, which was used in clinical trials to reactivate human neutrophil functions during sepsis. Moreover, we observed a significant increase of PAR(2) expression on cell surface of neutrophils from septic patients as compared with healthy volunteers. Together, our results indicate that PAR(2) may be involved in the pathophysiology of neutrophil-endothelial interactions during wound healing or later during sepsis in humans, potentially by affecting neutrophil apoptosis, transendothelial migration and Fcgamma receptor-mediated phagocytosis. PMID- 17845212 TI - Structural and functional alterations in the beta2-adrenoceptor are caused by a point mutation in patients with atopic eczema. AB - The density of beta2-adrenoceptors is significantly decreased in both keratinocytes and peripheral blood lymphocytes from patients with atopic eczema. Furthermore both cell types showed a sixfold increase in the K(D) for the specific binding of the non-specific antagonists (-)-[(3)H]CGP 12177 and [(125) I]CYP to keratinocytes and lymphocytes respectively compared with healthy controls. Based on these results polymorphism in the beta2-adrenoceptor gene was suspected. Consequently the entire intronless beta2-adrenoceptor gene was isolated from whole blood and by RT-PCR from keratinocyte extracts of nine patients with atopic eczema and four healthy controls. DNA sequence analysis of nine atopic eczema patients confirmed a substitution in codon (1618) GCC (Ala(119)) to GAC (Asp(119)). This point mutation is expressed on the third transmembrane helix only 13A away from the established agonist/antagonist binding site at Asp(113). Computer modelling of this third transmembrane helix revealed substantial structural changes in the mutant compared with the wild type. Epidermal keratinocytes were established from one patient with atopic eczema (homozygote), the mother (heterozygote) and one age-matched healthy control. Cells were grown in media containing different concentrations of l-phenylalanine and receptor densities were determined. The results showed that cells with atopic eczema showed an increased sensitivity to l-phenylalanine concentrations with a narrow homeostasis compared with healthy controls. The heterozygous mother was only 50% as sensitive as the child. In summary, the results indicate that atopic eczema is associated with a single point mutation in the beta2-adrenoceptor gene leading to an impaired adrenergic response in the epidermis of these patients. PMID- 17845213 TI - Generation of a prophylactic melanoma vaccine using whole recombinant yeast expressing MART-1. AB - Malignant melanoma is a potentially deadly form of skin cancer and people at high risk of developing melanoma will benefit from effective preventive intervention. Yeast can be used as an efficient vehicle of antigen loading and immunostimulation. Saccharomyces cerevisiae is not pathogenic to humans and can be easily engineered to express specific antigens. In this study, we have developed a melanoma vaccine using a yeast-based platform expressing a full length melanocyte/melanoma protein to investigate its utility as a prophylactic melanoma vaccine in a transplantable mouse melanoma model. Yeast was engineered and expanded in vitro without technical difficulties, administered easily with subcutaneous injection, and did not show adverse effects, indicating its practical applicability and favourable safety profile. Despite the lack of knowledge of dominant epitopes of the protein recognized by mouse MHC-class I, the vaccine protected mice from tumor development and induced efficient immune responses, suggesting that the precise knowledge of epitopic sequences and the matched HLA type is not required when delivering a full-length protein using the yeast platform. In addition, the vaccine stimulated both CD4(+) T cells and CD8(+) T cells simultaneously. This study provides a 'proof of principle' that recombinant yeast can be utilized as an effective prophylactic vaccine to target patients at high-risk for melanoma. PMID- 17845214 TI - A Polypodium leucotomos extract inhibits solar-simulated radiation-induced TNF alpha and iNOS expression, transcriptional activation and apoptosis. AB - In this report, we have examined the molecular basis of the photoprotective effect of a hydrophilic extract of the fern Polypodium leucotomos (PL) in vitro, using a solar simulator as the source of UV radiation (SSR). We found that pretreatment of human keratinocytes with PL inhibited SSR-mediated increase of tumor necrosis factor (TNF)-alpha and also abrogated nitric oxide (NO) production. Consistent with this, PL blocked the induction of inducible nitric oxide synthase (iNOS) elicited by SSR. In addition, PL inhibited the SSR-mediated transcriptional activation of NF-kappaB and AP1. Finally, we demonstrated that pretreatment with PL exerted a cytoprotective effect against SSR-induced damage, resulting in increased cell survival. Together, these data postulate a multifactor mechanism of protection not exclusively reliant on the antioxidant capability of PL, and strengthen the basic knowledge on the photoprotective effect of this botanical agent. PMID- 17845215 TI - Assessment of principal parabens used in cosmetics after their passage through human epidermis-dermis layers (ex-vivo study). AB - Concern is continuously raised about the safety of parabens which are present in most of the cosmetic preparations. In this investigation, methyl-, ethyl-, propyl and butyl paraben (MP, EP, PP, BP), in a commercial cosmetic lotion, were deposited on human skin fragments, collected after surgical operations. Permeated parabens were determined after their passage through human epidermis-dermis layers, fixed on Franz diffusion cells. Bovine serum albumin (3%) was employed as receptor fluid. Then, parabens were assessed by liquid chromatography. The objective of this research was to determine the permeation of these molecules through human epidermis-dermis layers, and their possible passage to body tissues and/or accumulation in skin layers. Two groups of experiments were performed. In the first experimental group (G1), unique doses of the cosmetic were deposited on skin fragments fixed on Franz cells (n = 6), at time 0 h, followed with different withdrawn times of the receptor fluid at 12, 24 and 36 h. G1 results demonstrated that parabens penetration was influenced by their lipophilicity: more lipophilic the parabens were (BP > PP > EP > MP), less they crossed the skin layers (BP < PP < EP < MP). The second experimental group (G2) was constituted of three equal deposits on each Franz cell (n = 6) at different hour times 0, 12 and 24 h followed with three withdrawn times of the receptor fluid at 12, 24 and 36 h. The G2 results indicated that investigated parabens had significant increasing permeations in skin layers. This situation provokes the accumulation of these molecules which were considered by some authors as the cause of skin toxicities and carcinogenicity. PMID- 17845216 TI - Increased cyclooxygenase expression and thymine dimer formation after repeated exposures of humans to low doses of solar simulated radiation. AB - The impact of repeated doses of solar simulated radiation (SSR) has not been evaluated, particularly to determine if photoadaptation and photoprotection develop over time. In this study, erythema, pigmentation, cyclooxygenase (COX)-1 and 2 expression and thymine dimer (dTT) formation were evaluated in the skin of irradiated subjects of phototype II or III. Groups of 7-10 volunteers were whole body irradiated with a low dose of SSR on each of 10 consecutive days followed by a single erythemal ultraviolet B (UVB) dose on a small body area, or irradiated only with the single erythemal UVB dose on a small body area, or irradiated with the low dose of SSR on each of 30 consecutive days, or were unirradiated. Erythema and pigmentation were measured 24 h after the final SSR or UVB, and skin biopsies collected for the assessment of COX(+) cells and dTT(+) nuclei. The repeated SSR exposures induced a small increase in pigmentation without erythema, and were slightly protective against the erythemal effects of the subsequent high UVB dose. The number of COX-1(+) and 2(+) cells increased as a result of 10-days SSR and rose still further after 30-days SSR, indicating that photoadaptation had not developed. The SSR exposures did not result in any protection against the further increase in COX-1 and 2 expression caused by the erythemal UVB dose. In contrast, for dTT formation, the repeated SSR exposures led to a limited degree of both photoadaptation and photoprotection. PMID- 17845217 TI - Characterization of liver X receptor expression and function in human skin and the pilosebaceous unit. AB - The nuclear receptors liver X receptor alpha (LXRalpha) and liver X-receptor beta (LXRbeta) have a well documented role in cholesterol homeostasis and lipid metabolism within tissues and cells including the liver, small intestine and macrophages. In keratinocytes, LXRs have been shown to up-regulate differentiation in vitro via increased transcription of proteins of the AP1 complex and to down-regulate proliferation in vivo. In this study, we provide a detailed description of the location and possible role of LXRs within human skin and its associated glands and appendages. Using RT-PCR, Western blotting and immunohistochemistry, we have demonstrated expression of LXRalpha and LXRbeta mRNA and proteins in whole human skin as well as within a range of primary and immortalized human cell lines derived from human skin, hair follicle and sebaceous glands. Furthermore, we have shown that synthetic LXR specific agonists GW683965 and TO901317 significantly inhibit cell proliferation in primary epidermal keratinocytes, immortalized N/TERT keratinocytes and the immortalized SZ95 sebocyte line, and significantly increase lipogenesis in SZ95 sebocytes. In addition, we showed that the synthetic agonist TO901317 significantly reduced hair growth, in vitro. PMID- 17845218 TI - Targeted ablation of Abcc1 or Abcc3 in Abcc6(-/-) mice does not modify the ectopic mineralization process. AB - Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by ectopic mineralization of connective tissues, with considerable intra- and interfamiliar phenotypic variability. PXE is caused by mutations in the ABCC6 gene, which encodes a transporter protein, MRP6, and targeted ablation of Abcc6 in mice recapitulates the manifestations of PXE. In this study, we examined the hypothesis that the expression of other members of the Abcc family may be altered in Abcc6 null mice, possibly explaining the phenotypic variability because of the functional overlap of these transporters. Analysis of the transcript levels of Abcc1-10 and 12 in the liver of Abcc6 (-/-) mice by quantitative RT-PCR indicated that the levels of other C family mRNAs were not significantly different from wild-type mice. Next, we developed Abcc6/1(-/-) and Abcc6/3(-/-) double null mice and examined them for tissue mineralization. Histopathologic examination, coupled with computerized morphometric analysis, and chemical assay of calcium x phosphate product in the muzzle skin of Abcc1(-/-) and Abcc3(-/-) mice did not reveal evidence of mineralization. Abcc6/1(-/-) and Abcc6/3(-/-) double knock-out mice exhibited connective tissue mineralization similar to that in Abcc6 (-/-) mice. These results emphasize the importance of the Abcc6 gene in the ectopic mineralization process and further suggest that other members of the Abcc family, particularly Abcc1 and Abcc3, do not modulate the effects of Abcc6 in this mouse model. PMID- 17845219 TI - The distribution of the coronary arteries in the Angora rabbit. AB - The aim of this study was to determine the origin, course, termination and anastomosing of the coronary arteries in Angora rabbits. Eight adult healthy male Angora rabbits were used. Coloured latex was injected into the ascending aorta. A. coronaria sinistra of the Angora rabbit had larger diameter than a. coronaria dextra. It was divided into r. proximalis atrii sinistri, r. interventricularis paraconalis and r. circumflexus sinister in six Angora rabbits as well as r. septi interventricularis in two. R. septi interventricularis that stem directly from a. coronaria sinistra in two animals and from r. interventricularis paraconalis in six was a principal vessel responsible for the septum interventriculare. R. marginis ventricularis sinistri originating from r. circumflexus sinister was the most prominent artery on the auricular surface of the heart. R. interventricularis subsinuosus was not detected in Angora rabbits examined. A. coronaria dextra, crossing the sulcus coronarius immediately after its origin, ran obliquely in direction of the sulcus interventricularis subsinuosus to supply the right portion of the heart. The ventricular and septal branches of a. coronaria sinistra and a. coronaria dextra ran subepicardially at the beginning then intramyocardially and mostly parallel to the muscle fibres as surrounded by a thin adipose tissue. Their atrial branches were seen continuously to run subepicardially. PMID- 17845220 TI - Computed tomography (CT) of the lungs of the dog using a helical CT scanner, intravenous iodine contrast medium and different CT windows. AB - The aim of this study was to determine the accuracy of helical computed tomography (CT) for visualizing pulmonary parenchyma and associated formations in normal dogs. CT scan was performed by using intravenous contrast medium and by applying different types of CT windows: soft tissue and lung windows, and high resolution computed tomography of the lung. This technique allowed, especially with lung window types, a good view of the parenchyma, bronchial tree, vascular structures and pleural cavity. The selected images, with high anatomical quality and tissue contrast, may be a reference for future clinical studies of this organ. Thus, helical CT is a promising non-invasive method of diagnosing a wide variety of pulmonary diseases in dogs. PMID- 17845221 TI - Ultrastructural characteristics of blood cells of juvenile loggerhead sea turtles (Caretta caretta). AB - Ultrastructural characteristics of erythrocytes, heterophils, eosinophils, lymphocytes, monocytes and thrombocytes of the loggerhead sea turtle (Caretta caretta) were evaluated, using blood samples from 15 healthy juvenile animals. Except for the eosinophils, the rest of the white blood cells from loggerhead turtles had similar ultrastructural characteristics compared with blood cells from other sea turtle species. Eosinophils from loggerhead turtles were homogeneous in size, and no crystalline structures were observed within the granules. This paper provides an ultrastructural characterization of blood cells of loggerhead sea turtles, as a reference for future haematological studies of this species. PMID- 17845222 TI - An immunohistochemical study of the distribution of intermediate filaments in the ovary of the emu (Dromaius novaehollandiae). AB - The immunohistochemical localization of the intermediate filaments desmin, vimentin and smooth muscle actin (SMA) in the ovary of the emu was described in the present study. The cortical region of the ovary contained developing and atretic primordial, pre-vitellogenic and vitellogenic follicles. Vimentin immunostaining was demonstrated in the granulosa cell layer of primordial, pre vitellogenic and vitellogenic developing and atretic follicles. An interesting finding of the present study was the localization of SMA in fibroblasts located in the theca externa of late vitellogenic follicles. The presence of SMA in these fibroblasts suggests that they possess characteristics of smooth muscle cells. PMID- 17845223 TI - A lectin histochemical study on the testis of the babirusa, Babyroussa babyrussa (Suidae). AB - The distribution of lectin bindings in the testis of babirusa, Babyrousa babyrussa (Suidae) was studied histochemically using 10 biotinylated lectins, Peanut agglutinin (PNA), Ricinus communis agglutinin (RCA I), Dolichos biflorus agglutinin (DBA), Vicia villosa agglutinin (VVA), Soybean agglutinin (SBA), Wheat germ agglutinin (WGA), Lens culinaris agglutinin (LCA), Pisum sativum agglutinin (PSA), Concanavalin A(Con A) and Ulex europaeus agglutinin (UEA I). Nine of 10 lectins showed a variety of staining patterns in the seminiferous epithelium and interstitial cells. The acrosome of Golgi-, cap- and acrosome-phase spermatids displayed various PNA, RCA I, VVA, SBA and WGA bindings, indicating the presence of glycoconjugates with D-galactose, N-acetyl-D-galactosamine and N-acetyl-D glucosamine sugar residues respectively. No affinity was detected in the acrosome of late spermatids. LCA, PSA and Con A which have affinity for D-mannose and D glucose sugar residues were positive in the cytoplasm of spermatids and spermatocytes. DBA was positive only in spermatogonia. In addition to DBA, positive binding in spermatogonia was found for VVA, WGA and Con A, suggesting the distribution of glycoconjugates with N-acetyl-D-galactosamine, N-acetyl-D glucosamine, D-mannose and D-glucose sugar residues. Sertoli cells were stained intensely with RCA I, WGA and Con A. In Leydig cells, RCA I and Con A were strongly positive, while WGA, LCA and PSA reactions were weak to moderate. The present findings showed that the distribution pattern of lectin binding in the testis of babirusa is somewhat different from that of pig or other mammals reported previously. PMID- 17845224 TI - Effect of preservation methods on the performance of bovine pericardium graft in a rat model. AB - This study investigates the effect of preservation methods on the performance of bovine parietal pericardium grafts in a rat model. Mid-ventral full thickness abdominal wall defects of 3 x 2.5 cm in size were created in 90 male Sprague Dawley rats (300-400 g), which were divided into three groups of 30 rats each. The abdominal defects of group one and two were repaired with lyophilized and glycerolized bovine pericardium grafts, while the defects of group three were repaired with expanded polytetrafluoroethylene (ePTFE) Mycro Mesh as a positive control. Another group of 30 rats underwent sham operation and was used for comparison as negative control. Each group of rats (n = 30) was divided into five subgroups (n = 6) and killed at 1, 3, 6, 9 and 18 weeks post-surgery for gross and morphological evaluations. The rats tolerated the surgical procedure well with a total mortality of 0.05%. No serious post-operative clinical complications or signs of rejection were encountered. Adhesions between the grafts and the underlying visceral organs observed in the study were mostly results of post surgical complications. Glycerol preservation delayed degradation and replacement of the grafts, whereas lyophilization caused early resorption and replacement of the grafts. The glycerolized grafts were replaced with thick dense fibrous tissue, and the lyophilized grafts were replaced with thin loose fibrous tissue. The healing characteristic of the bovine pericardium grafts was similar to those of the sham-operated group, and quite different from those of the ePTFE Mycro Mesh. The outcome of the present study confirmed the superiority of glycerolized bovine pericardium grafts over its lyophilized counter part. PMID- 17845225 TI - Gene expression of secretory carbonic anhydrase isozymes in striated ducts of canine salivary glands using laser microdissection system. AB - To clarify whether striated duct cells in canine salivary glands synthesize secretory carbonic anhydrase (CA-VI), as is the case with serous acinar cells, the present study utilized laser microdissection to harvest striated duct cells from canine parotid and submandibular glands, and total RNA extracted from these cells was then amplified by reverse transcription-polymerase chain reaction to assess CA-VI gene expression. The results confirmed the local expression of CA-VI mRNA in striated duct cells. This clarified that, in canine salivary glands, CA VI is synthesized in not only serous acinar cells, but also striated duct cells. PMID- 17845226 TI - Changing caveolin-1 and oxytocin receptor distribution in the ageing human prostate. AB - Several observations suggest that caveolin-1 has an important role in control of cell proliferation and cancerogenesis. For instance, oxytocin provokes a proliferative response in the prostate tissue when the oxytocin receptor is localized mainly in caveolin-1-enriched domains and an anti-proliferative effect when the same receptor is not localized in caveolae. Moreover, oxytocin concentrations are elevated in prostate tissue of patients with benign prostatic hyperplasia (BPH). In this study the expression pattern of the molecules caveolin 1, oxytocin receptor, androgen receptor and p21 (cell cycle arrest indicator) was investigated in the prostate tissue of BPH patients and of young controls. We found that both caveolin-1 and oxytocin receptor expression is drastically increased with age in both smooth muscle and epithelium of the prostate. We also found a significantly increased co-localization of the oxytocin receptor with caveolin-1 in both the muscle and the epithelium, especially in BPH patients. Androgen receptor and p21 staining was found throughout the prostate but did not change significantly with age or in BPH patients. We conclude that oxytocin may have a proliferative effect on the prostate tissue through the caveolae associated receptors and thus contribute to BPH. This process seems to be androgen receptor independent. PMID- 17845227 TI - Papillar morphology of the rumen of forest reindeer (Rangifer tarandus fennicus) and semidomesticated reindeer (R. t. tarandus). AB - The papillar morphology of the ventral and dorsal rumen of the wild forest reindeer (Rangifer tarandus fennicus Lonn.) and semidomesticated reindeer (R. t. tarandus L.) was studied in October and November 1996. The morphological measurements which were carried out were: the lengths of the papillae, the number of the papillae per square centimetre, the cross-sectional area and perimeter of sections cut from the middle of papillae. From these measurements mean papillar volume, areal papillar volume, mean papillar (epithelial) surface area, areal papillar surface and surface enlargement factor were calculated. No differences in these measurements between ventral and dorsal walls of the rumen were evident. The semidomesticated reindeer had longer papillar perimeters, larger mean and areal papillar surface areas, larger mean papillar volumes, and a larger surface enlargement factor in the ventral rumen than did forest reindeer. This may be a result of differences between feeding habits, the semidomesticated reindeer preferring a diet including more plants rich in carbohydrates e.g. lichens, which has resulted in a high production of volatile fatty acids and thus stimulation of papillar growth. PMID- 17845228 TI - Microscopic characterization of teeth of pacas bred in captivity (Agouti paca, Linnaeus, 1766). AB - The microscopic description of the teeth of pacas (Agouti paca) bred in captivity was developed for providing biological data on one of the largest American wild rodents, as not many references exist in the literature about this species. Two newborn males, two adult males (9 and 72 months old), one newborn female and two adult females (30 and 54 months old) were used after death due to fights, neonatal cannibalism or unknown causes. Animals were radiographed, and their teeth were extracted and put on an acrylic resin block, cut on a diamond-like disc microtome and diaphanized. It was noted that enamel surrounds the coronary dentine and projects to the root region, besides being present as internal laminae, arranged in a parallel way and in the vestibulolingual direction. The dentine is located between the enamel laminae and surrounds the pulp horns. The cementum is located internal to the enamel laminae. From scanning electronic microscopy, we find that the enamel is the outer element on the vestibular surface, and it is in direct contact with the dentine. On the lingual surface, the cementum and dentine are the outer elements. PMID- 17845229 TI - Expression of neuronal nitric oxide synthase in the pancreas of the sheep. AB - In numerous mammals, nitric oxide (NO) influences the activity of the exocrine and endocrine pancreas. In this study, immunocytochemistry was utilized to investigate the expression of neuronal nitric oxide synthase (nNOS) in the pancreas of sheep. In double immunocytochemical staining, the co-localization of nNOS with vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY) or substance P (SP) was studied. The presence of nNOS was confined to the intrapancreatic neurones (9.6 +/- 1.3%) as well as to nerve fibres of the endocrine pancreas and intrapancreatic ganglia. nNOS-immunoreactive (IR) neurones were round and oval in shape and predominantly (83.3 +/- 2.6%) belonged to the middle-size group (25-50 mum). Numerous, fine islets supplying nNOS-IR nerve terminals were devoid of VIP, SP or NPY. Moderately numerous, non-varicose nNOS IR nerve fibres of intrapancreatic ganglia frequently expressed VIP or NPY, but not SP; 2.2 +/- 0.6% of nNOS-IR intrapancreatic neurones displayed lack of VIP, whereas 7.5 +/- 0.8% were VIP-IR. All nNOS-IR neurones were devoid of SP. The frequencies of nNOS-IR/NPY-IR and nNOS-IR/NPY-negative intrapancreatic neurones were 2.2 +/- 0.4% and 6.1 +/- 1.1%, respectively. Comparison with other mammals indicated that nitrergic innervation of the ovine pancreas is species-determined and may be a reflection of the ruminants' digestion specificity. The possible origin of nNOS-IR nerve fibres and functional significance of NO in the pancreas of sheep were discussed. PMID- 17845234 TI - Abstracts of the 10th International Symposium and 12th Annual Meeting of the Society for the Study of Behavioural Phenotypes, Sacramento, California, USA, 11 13 October 2007. PMID- 17845230 TI - Optimized architecture for nutrition in the avascular retina of Megachiroptera. AB - Investigations were undertaken to evaluate the unique choroidal vascular system of the Megachiroptera (fruit bats) and its possible significance for retinal nutrition. Fluorescein angiography was performed and documented on Pteropus poliocephalus. Vascular casts were made of the eye of Pteropus scapulatus. Histologic evaluation was performed on P. scapulatus. Results confirmed that each papilla has a vascular core, and a unique vascular system emanating from the optic disc. The histological appearance of the choroid and retina of P. scapulatus confirmed a vascular core to the papillae with a thin, but definite Bruch's membrane. Megachiroptera have a unique vascular system to supply nutrition to the retina consisting of capillary loops within a dense, uniform mosaic of choroidal projections or papillae, which permit the diffusion of metabolites to the retina and a heretofore undescribed vascular tuft emanating from the optic disc. We suggest that this vascular system provides nutrition by diffusion to a thick avascular retina, without any shadowing by vessels, and allows for nocturnal visual acuity and light-gathering capabilities. PMID- 17845235 TI - Intellectual abilities in a large sample of children with Velo-Cardio-Facial Syndrome: an update. AB - BACKGROUND: Learning disabilities are one of the most consistently reported features in Velo-Cardio-Facial Syndrome (VCFS). Earlier reports on IQ in children with VCFS were, however, limited by small sample sizes and ascertainment biases. The aim of the present study was therefore to replicate these earlier findings and to investigate intellectual abilities in a large sample of children with VCFS. In addition, we aimed to identify factors that may contribute to within syndrome variability in cognitive performance, such as the mode of inheritance of the deletion, sex, the presence of a heart defect and psychiatric morbidity. METHOD: IQ data of 103 children with VCFS (56 males, 47 females) were collected. Psychiatric diagnosis was additionally recorded. RESULTS: Children with VCFS had a mean full-scale IQ (FSIQ) of 73.48 (range: 50-109). There were no effects of sex, presence of a heart defect and psychiatric condition on intellectual profile. Inheritance of the deletion affected cognitive performance in VCFS, with children with familial deletions having significant lower FSIQ than children with a de novo deletion. CONCLUSIONS: Learning disabilities are very common in children with VCFS, although marked within syndrome variability is noted. One factor contributing to this variability seems to be the mode of inheritance of the deletion. PMID- 17845236 TI - The behavioural phenotype of Cornelia de Lange Syndrome: a study of 56 individuals. AB - BACKGROUND: Few studies have investigated functional and behavioural variables of Cornelia de Lange Syndrome (CdLS) in a large sample of individuals. The aim of this study is to provide greater insight into the clinical, behavioural and cognitive characteristics that are associated with CdLS. METHODS: In total, 56 individuals with CdLS participated in the study. During hospitalization, their mothers received a number of questionnaires to complete. The behavioural phenotype was investigated using the following scales: Developmental Behaviour Scale Primary Carer Version; Autism Behaviour Checklist; Childhood Autism Rating Scale. RESULTS: Our participants demonstrated some behavioural characteristics that are frequently associated with CdLS (hyperactivity, attention disorder, anxiety, compulsive disorders, self-injurious behaviour and autistic-like features). Our findings demonstrate the variability of behavioural characteristics in CdLS in addition to highlighting the contribution of some variables to both the CdLS behavioural profile and the developmental trajectory of the behavioural pattern. CONCLUSIONS: The behavioural characteristics identified in our sample were correlated with some clinical and functional aspects (chronological age, cognitive level and clinical phenotype). The variability of the behavioural profile in CdLS reflected the wide variability in cognitive and adaptive functioning across individuals and led us to conclude that there may be multiple behavioural phenotypes associated with the syndrome. Further comparative studies between CdLS and individuals with intellectual disability or other genetic syndromes may help to provide further understanding of the behavioural phenotype of CdLS. PMID- 17845237 TI - Siblings of individuals with autism or Down syndrome: effects on adult lives. AB - BACKGROUND: In this study, we examine instrumental and affective involvement in the sibling relationship for adults who have a brother or sister with an autism spectrum disorder (ASD) or Down syndrome (DS). We ask three research questions: (1) How do adult siblings of individuals with ASD differ from siblings of individuals with DS in their assessment of the quality of the sibling relationship and their experience of growing up with a brother or sister with a disability? (2) Are there gender effects on the sibling relationship and sibling experience in these two groups? (3) Which factors are predictive of variation in the sibling relationship for siblings of adults with ASD or DS? METHODS: Data from 154 siblings who participated in two linked longitudinal studies were used. Seventy-seven siblings with a brother or sister with ASD were matched by age and gender to 77 siblings with a brother or sister with DS. The siblings in each group were between 21 and 56 years of age and over half were sisters. Siblings completed questionnaires on instrumental and affective involvement with their brother or sister with ASD or DS, the impact of growing up with a brother or sister with a disability on their lives, and their coping skills and feelings of pessimism. RESULTS: Compared with the siblings of adults with DS, siblings of adults with ASD had less contact with their brother or sister, reported lower levels of positive affect in the relationship, felt more pessimistic about their brother or sister's future, and were more likely to report that their relationships with their parents had been affected. For siblings of adults with ASD, a closer sibling relationship was observed when the sibling had lower educational levels, lived closer to the brother or sister with ASD, used more problem-focused coping strategies, and when his or her brother or sister with ASD had higher levels of functional independence. In contrast, for siblings of adults with DS, a closer sibling relationship was observed when the sibling did not have children, had lower levels of education, lived closer to the brother or sister with DS, when he or she used more problem-focused coping, was less pessimistic about the brother or sister's future, and when his or her life had been impacted to a greater extent by growing up with a brother or sister with DS. CONCLUSIONS: We discuss the implications of these findings for future caregiving roles for siblings. Siblings of individuals with ASD may face difficulty when their parents are no longer able to be the primary caregivers for their brother or sister with ASD, as they tend to have less emotional closeness and are more pessimistic about their brother or sister's future than siblings of individuals with DS. Moreover, in both groups, a closer sibling relationship was observed when the sibling used more problem-focused coping strategies, which may have implications for intervention. PMID- 17845238 TI - Infant attentional behaviours as prognostic indicators in Cornelia-de-Lange syndrome. AB - BACKGROUND: Cornelia-de-Lange syndrome is a rare congenital syndrome with poor social relatedness as one of several characteristics of its behavioural phenotype. METHODS: Video observations were collected from seven children in their first year of life and again with age 2-4 years. Data were analysed for distribution of object-related and social attention and for relationships between early and later observations. RESULTS: The findings suggest some inter-individual stability for social relatedness. CONCLUSIONS: Low frequency of eye-contact in early interaction may serve as a risk factor. Intensive early interaction is recommended in early stimulation programmes. PMID- 17845239 TI - Evidence of resilience in families of children with autism. AB - BACKGROUND: Family resilience is a growing field of inquiry, investigating factors that contribute to a family's becoming stronger in spite of dealing with adversity. Despite the growing interest in studying family resilience, the topic has not been explored in families with children who have disabilities. This report, a part of a larger study--using both quantitative and qualitative methodologies--is an examination of factors of family resilience in the families of children with autism. Evidence of family resilience such as family connectedness and closeness, positive meaning-making of the disability, and spiritual and personal growth were identified and examined in this part of the study. METHOD: The study uses a survey methodology, analysing responses to several rating scales and written responses to three open-ended questions. Survey respondents consisted of 175 parents and other primary caregivers of a child with autism--ages between 2 and 18 years. RESULTS: Results suggest identification of specific resilience processes, such as: making positive meaning of disability, mobilization of resources, and becoming united and closer as a family; finding greater appreciation of life in general, and other people in specific; and gaining spiritual strength. CONCLUSIONS: This study presents evidence that a considerable number of families of children with autism display factors of resilience--reporting having become stronger as a result of disability in the family. PMID- 17845240 TI - Prevalence of intellectual disability: a comprehensive study based on national registers. AB - BACKGROUND: Based on standard social benefit registers, the prevalence of intellectual disability (ID) in Finland is estimated to be 0.6%, while epidemiological surveys yield 1.1%. Combining several registers, our aim was to find a more reliable estimate of the prevalence of ID, especially among children and adolescents. This is important when special or inclusive general services are planned to meet the various needs of people with ID. METHOD: A survey based on eight national health and social benefit registers. RESULTS: Combining different registers yielded a mean ID prevalence of 0.70% (95% CI 0.69-0.70%), with marked differences according to sex and age group (range 0.38-0.96%). Capture-recapture analysis gave higher prevalence estimates (range 0.57-1.08%). CONCLUSIONS: When several health and social benefit registers are surveyed, the estimated prevalence of ID increases, approaching that obtained in epidemiological surveys. PMID- 17845241 TI - Symptoms of dementia among adults with Down's syndrome: a qualitative study. AB - BACKGROUND: Dementia is common among adults with Down's syndrome (DS); yet the diagnosis of dementia, particularly in its early stage, can be difficult in this population. One possible reason for this may be the different clinical manifestation of dementia among people with intellectual disabilities. AIMS: The aim of this study was to map out the carers' perspective of symptoms of dementia among adults with DS in order to inform the development of an informant-rated screening questionnaire. METHOD: Unconstrained information from carers of people with DS and dementia regarding the symptoms, particularly the early symptoms of dementia, was gathered using a qualitative methodology. Carers of 24 adults with DS and dementia were interviewed. The interviews were recorded and fully transcribed. The transcripts were then analysed using qualitative software. RESULTS: There appeared to be many similarities in the clinical presentation of dementia in adults with DS and the non-intellectually disabled general population. Like in the non-intellectually disabled general population, forgetfulness especially, impairment of recent memory combined with a relatively intact distant memory and confusion were common, and presented early in dementia among adults with DS. However, many 'frontal lobe'-related symptoms that are usually manifested later in the process of dementia among the general population were common at an early stage of dementia among adults with DS. A general slowness including slowness in activities and speech, other language problems, loss of interest in activities, social withdrawal, balance problems, sleep problems, loss of pre-existing skills along with the emergence of emotional and behaviour problems were common among adults with DS in our study. CONCLUSIONS: This study highlights the similarities in the clinical presentation of dementia among the general population and people with DS with a particular emphasis on the earlier appearance of symptoms associated with the frontal lobe dysfunction among adults with DS. PMID- 17845243 TI - Venice Arrhythmias 2007. Abstracts. PMID- 17845244 TI - Effects of a dietary application of a yeast cell wall extract on innate and acquired immunity, on oxidative status and growth performance in weanling piglets and on the ileal epithelium in fattened pigs. AB - Potential immunomodulatory effects of a cell wall extract from Saccharomyces cerevisiae (Y; Antaferm MG) were tested in pigs: in trial I, 0.03% Y and in trial II 0.3% Y was used. Based on earlier observations that Y may increase feed intake, two treatment groups, Y-a (fed ad libitum) and Y-r (fed restrictively) were studied in comparison with a control group (C) in both trials. Y-r received the amount of feed consumed by C. Immune status was surveyed by determining phagocytic activity and oxidative burst of neutrophils and blood concentrations of haptoglobin (Hp), and immunoglobulin (Ig) G and A. Oxidative stress was monitored by recording reactive oxygen metabolites (ROM) and total antioxidant capacity. In a third trial, fattened pigs were used for morphological and immunohistochemical studies (IgM and IgA as well as CD4(+) and CD8(+) T cells) in ileal epithelium. Pigs fed 0.03% Y for 2 weeks prior to slaughter were compared with the C group. Feed intake was identical in the Y-a and Y-b groups and data subsets were accordingly pooled. Treatment and time as well as treatment x time interactions were detectable for most of the parameters studied, but a distinct immunomodulatory effect of Y was not consistently identifiable and performance did not improve. In trial III, the intestinal parameters investigated were not different between Y and C. PMID- 17845245 TI - Yttrium oxide (Y2O3) as an inert marker in digestibility studies with dogs, blue foxes and mink fed diets containing different protein sources. AB - The study evaluated the use of yttrium oxide (Y(2)O(3)) as an inert marker in studies of apparent total tract digestibility in dogs, blue foxes and mink. Comparison was made with total faecal collection, and use of chromic oxide (Cr(2)O(3)) as marker respectively. Four experimental diets were added 0.1 g/kg yttrium oxide and 10 g/kg chromic oxide and fed to four animals of each species. Faecal recovery of yttrium oxide was 94.4% (SEM +/- 1.0), and of chromic oxide 105.8% (SEM +/- 1.5). The digestibilities of dry matter, crude protein, crude fat, starch and total carbohydrates obtained by total collection and yttrium oxide as marker showed close similarity, and in most cases not significant differences, independent of species and diets. In dogs, overall digestibilities of main nutrients with chromic oxide as marker were not significantly different from overall means obtained with yttrium oxide (p > 0.05). Overall digestibility of dry matter, crude protein and total carbohydrates in blue foxes and mink was significantly higher with chromic oxide than with yttrium oxide (p < 0.05). In dogs and blue foxes, digestibilities of individual amino acids determined by use of yttrium oxide were not different from values obtained using total collection of faeces, both within diets and for overall mean (p > 0.05). Overall amino acid digestibilities in dogs determined with chromic oxide as marker were similar to corresponding figures for yttrium oxide, whereas use of chromic oxide resulted in significantly higher digestibilites for a number of amino acids compared with yttrium oxide in foxes and mink (p < 0.05). The digestibilities of most main nutrients and amino acids revealed no interaction between diet and method (p > 0.05). The study showed that yttrium oxide can be used in low concentration in the feed, and allows high accuracy of analyses and thereby precise digestibility determination. It is concluded that yttrium oxide is an alternative inert marker to chromic oxide in the studied species. PMID- 17845246 TI - Insulin-like growth factor I in growing thoroughbreds. AB - The objective of this longitudinal study was to characterize growth and plasma insulin-like growth factor I (IGF-I) concentrations in pasture-raised thoroughbreds fed two sources of dietary energy. Mares and foals were randomly assigned to either a sugar and starch (SS) or fat and fibre (FF)-rich feed, and plasma IGF-I and growth were measured once a month from 1 to 16 months of age. These dependent variables were also compared with day length and ambient temperature. There was an association between plasma IGF-I concentration and average daily gain (ADG) (r = 0.32, p < 0.001). There were also clear seasonal patterns in both ADG and plasma IGF-I, with high values in June and May, and a low value in March. Plasma IGF-I and ADG were positively associated with day length and temperature. Plasma IGF-I was never higher (p > 0.10) in the FF group when compared with the SS group, and was higher in the SS group during a rapid growth phase in the spring of year 2 (p < 0.10). The results establish an association between ADG and IGF-I in the horse and indicate that environment and age may influence this relationship. In addition, plasma IGF-I is influenced by dietary energy source at particular times of year. This link has important implications in designing feeding management strategies that are aimed at addressing skeletal development. PMID- 17845247 TI - Oestradiol, but not genistein, inhibits the rise in food intake following gonadectomy in cats, but genistein is associated with an increase in lean body mass. AB - The prevalence of obesity in domestic cats is increasing worldwide, and is strongly associated with gonadectomy. We have previously demonstrated the effectiveness of oestradiol in reducing food intake in both male and female neutered cats. This experiment was designed to test the hypothesis that oestradiol or genistein would prevent the increase in food intake following gonadectomy of male and female cats, and would prevent an increase in body fat mass. Three groups of eight cats each were surgically neutered then treated daily with either 0.5 mug oestradiol subcutaneously, 100 mg/kg genistein orally, or vehicle only. Effect of treatment on food intake, vaginal cytology and body weight were recorded, and body composition was assayed using the D(2)O isotopic dilution method. Neutering was followed by an increase in food intake, bodyweight and body fat mass in the control group, which were almost completely prevented by treatment with oestradiol (p < 0.001). Treatment with genistein had no effect on food intake or bodyweight increase, but was associated with a significant increase in lean body mass (p = 0.018), and significantly less body fat accumulation than the control group (p = 0.01). There were no significant differences in responses to treatment between sexes. These findings demonstrate the importance of gonadal oestrogen for the control of food intake in male and female cats, and suggest the provision of an oestrogenic compound could help prevent obesity following neutering. In addition, the findings of this study are consistent with observations in rodents of the efficacy of genistein in inhibiting adipogenesis and promoting lean body tissue development. PMID- 17845248 TI - Growth and parameters of microflora in intestinal and faecal samples of piglets due to application of a phytogenic feed additive. AB - A commercial phytogenic feed additive (PFA), containing the fructopolysaccharide inulin, an essential oil mix (carvacrol, thymol), chestnut meal (tannins) and cellulose powder as carrier substance, was examined for effects on growth and faecal and intestinal microflora of piglets. Two experiments (35 days) were conducted, each with 40 male castrated weaned piglets. In experiment 1, graded levels of the PFA were supplied (A1: control; B1: 0.05% PFA; C1: 0.1% PFA; D1: 0.15% PFA) in diets based on wheat, barley, soybean meal and fish meal with lysine as the limiting amino acid. In experiment 2, a similar diet with 0.1% of the PFA (A2: control; B2: 0.1% PFA; C2: +0.35% lysine; D2: 0.1% PFA + 0.35% lysine) and lysine supplementation was utilized. During experiment 1, no significant effect of the PFA on growth, feed intake and feed conversion rate was observed (p > 0.05). Lysine supplementation in experiment 2 improved growth performance significantly, but no significant effect of the PFA was detected. Microbial counts in faeces (aerobes, Gram negatives, anaerobes and lactobacilli) during the first and fifth week did not indicate any significant PFA effect (p > 0.05). In addition, microflora in intestinal samples was not significantly modified by supplementing the PFA (p > 0.05). Lysine supplementation indicated lysine as limiting amino acid in the basal diet, but did not influence the microbial counts in faeces and small intestine respectively. PMID- 17845249 TI - In vitro fermentation of different starches by mixed micro-organisms from the sheep rumen. AB - Fermentation characteristics of wheat, rye, maize and triticale starches by mixed micro-organisms from the sheep rumen were determined in an in vitro experiment. Starch was incubated with ruminal fluid for 2, 4, 6, 8, 10 and 12 h and various fermentation variables were determined. The rates of fermentation of the starches were not different (p > 0.05) from each other except for 2 and 4 h of incubation. Likewise, net ammonia production, sugar utilization, microbial biomass and the efficiency of microbial protein synthesis did not differ between the starches (p > 0.05). The proportions of sugar utilized were similar between the starches and approximately 75% of the starches were fermented during the 12-h incubation. The 12-h net concentrations of individual and total volatile fatty acids (VFA) were affected (p < 0.05) by the type of starch. The concentrations of acetate, propionate and butyrate and that of total VFA from wheat, maize and triticale incubations were higher (p < 0.05) than those from rye incubation. The results suggest that the type of starch subject to investigation had no measurable effects on fermentation variables determined in this study except for individual and total VFA concentrations. PMID- 17845250 TI - No impact of a phytogenic feed additive on digestion and unspecific immune reaction in piglets. AB - Two 35 day experiments were conducted to examine the influence of a commercial phytogenic feed additive (PFA) on nutrient digestibility and unspecific immune reaction of piglets in the post-weaning period. The PFA composition was inulin, an essential oil mix (carvacrol and thymol), chestnut meal (tannins), and cellulose powder as carrier substance. In each experiment, immediately after weaning 40 male castrated piglets were divided into four experimental groups (n = 10). Diets were based on wheat, barley, soy bean meal and fishmeal using lysine as the first limiting amino acid. In experiment 1, graded levels of the PFA were supplied (A: control; B: 0.05% PFA; C: 0.1% PFA; D: 0.15% PFA). Experiment 2 utilized equal diets with 0.1% of the PFA, but different lysine supply (A: control; B: 0.1% PFA; C: +0.35% lysine; D: 0.1% PFA + 0.35% lysine). At the end of the experimental period, acute phase proteins (APPs) haptoglobin and C reactive protein were examined in individual blood plasma samples. Following each growth study, 16 animals (n = 4) were taken for sampling of ileal chyme and assessing of praecaecal digestibility of protein and amino acids. In addition, digesta samples of the duodenum and the total pancreatic tissue were utilized for determining the enzyme activity of alpha-amylase and trypsin. APP, praecaecal digestibility and enzyme activities did not significantly respond to the PFA supplementaion in diets. PMID- 17845251 TI - Effects of Fusarium toxins on growth, humoral immune response and internal organs in weaner pigs, and the efficacy of apple pomace as an antidote. AB - A feeding trial using 220 weaner pigs which comprised two experimental series was conducted to investigate the effects of diets contaminated with the Fusarium toxins deoxynivalenol (DON) and zearalenone (ZON) and to test the hypothesis that apple pomace acts as an antidote to these mycotoxins. Two diets without contaminated wheat, containing either no pomace or 8% pomace, and two diets with naturally contaminated wheat (3.2 mg DON and 0.06 mg ZON, and 2.1 mg DON and 0.25 mg ZON per kg diet in series 1 and 2 respectively), containing either no pomace or 8% pomace were fed ad libitum for 5 weeks. Mycotoxin exposure lowered feed intake (p < 0.01) and growth (p = 0.05), and tended to decrease the energy conversion ratio (p = 0.06). Although the intake of apple pomace did not increase feed intake, it increased the growth rate (p = 0.04), mainly by restoring growth in the presence of mycotoxins (p = 0.08 for the interaction mycotoxin x pomace). In the first experimental series, the animals were immunized with a parvovirus vaccine. The percentage of seroconverting animals did not differ between the treatments (p = 0.56), which indicates that DON did not affect the humoral immune response. In the second experimental series, female piglets fed the contaminated diets had heavier uteri than piglets fed the uncontaminated diets (p < 0.01), regardless of pomace supplementation. The results show that pomace may alleviate the negative effect of DON on growth but does not counteract the hormonal effects of ZON. PMID- 17845252 TI - Effects of steroidal implantation and ractopamine-HCl on nitrogen retention, blood metabolites and skeletal muscle gene expression in Holstein steers. AB - Six Holstein steers (231 +/- 17 kg) housed in metabolism crates were used in a randomized complete block design with three blocks of two steers based on previous serum insulin-like growth factor (IGF)-I concentrations. One of the two steers in each block was implanted with 120 mg trenbolone acetate and 24 mg oestradiol-17beta on day 0. None of the steers was fed ractopamine-HCl in the initial 28 days, and then all steers were fed 200 mg of ractopamine-HCl per steer daily from day 28 until the end of the trial. Steers were fed a corn-based diet (62% rolled corn, 20% expeller soya bean meal and 15% alfalfa hay) twice daily with an average dry matter intake of 4.8 kg/day. Blood and M. longissimus biopsy samples were collected prior to implantation and on days 14, 28, 42 and 56. There was an implant x ractopamine interaction for retained nitrogen (p < 0.05); ractopamine feeding led to only small improvements in nitrogen retention for implanted steers (45.9 g/day vs. 44.5 g/day), whereas ractopamine led to larger increases in nitrogen retention for non-implanted steers (39.0 g/day vs. 30.4 g/day). Implantation increased (p < 0.05) and ractopamine tended to decrease (p = 0.06) serum IGF-I concentrations. Implantation tended to increase (p = 0.16) and ractopamine decreased (p < 0.05) mRNA expression of IGF-I in the M. longissimus. Ractopamine decreased mRNA expression of beta(1)- and beta(2)-receptors in M. longissimus (p 0.05; and summary OR = 1.31, 95% CI 0.98-1.75, P > 0.05, respectively). In both analyses, the separate integration of four RCTs transfusing red blood cells (RBCs) or whole blood filtered after storage showed an association between non-WBC-reduced ABT and postoperative infection, whereas the separate integration of six (or nine) RCTs, reported through 2002 or 2005, and transfusing prestorage-filtered RBCs showed no association, whether intention to-treat or as-treated comparisons were used. Thus, the published meta-analyses have produced discordant results because they did (or did not) investigate medical sources of heterogeneity and did (or did not) include the most recent RCTs. Intention-to-treat and as-treated comparisons produced concordant results. PMID- 17845257 TI - Parvovirus B19 genotypes 1 and 2 detection with real-time polymerase chain reaction assays. AB - BACKGROUND AND OBJECTIVES: Parvovirus B19 (B19V) DNA screening has been introduced to comply with European regulations for certain plasma products. Current commercial and some in-house B19V DNA assays fail to detect or under quantify the recently identified genotypes 2 and 3. In this report, we describe 2 year experience with B19V DNA screening using the commercial assay from Roche (detecting only genotype 1) combined with an in-house assay (detecting genotypes 1, 2 and 3). This dual testing approach enables the identification of molecular variants of B19V. MATERIALS AND METHODS: Between 2005 and 2007, approximately 2.6 million plasma donations were screened for B19V DNA loads exceeding 10(6) IU/ml using the Roche and the in-house real-time polymerase chain reaction assay. RESULTS: A total of 232 plasma units were identified with B19V DNA loads above 10(6) IU/ml. Concordant results were observed for the majority of B19V positive samples; however, three of these showed discrepant results between the two assay systems. One was a B19V genotype 2 strain not detected by the Roche assay; another was a B19V genotype 1 strain with a mismatch in the 3'-end of the reverse primer and therefore under-quantified by the Roche assay; and the third one was also a B19V genotype 1 strain that gave an unusual amplification plot in the in house assay due to a mismatch in the probe-binding site. CONCLUSIONS: New, high viral load, B19V genotypes 2 and 3 infections are rare in blood donors tested by Sanquin. One case was found while testing 2.6 million donations. The prevalence of B19V genotype 1 variants not detected by commercial or in-house assays might be in the same range or even higher than the prevalence of B19V genotype 2 viruses, which remain undetected. PMID- 17845258 TI - Improved detection of acute parvovirus B19 infection by immunoglobulin M EIA in combination with a novel antigen EIA. AB - BACKGROUND AND OBJECTIVES: Although parvovirus B19 is a significant blood product contaminant, few methods other than polymerase chain reaction (PCR) have been developed to detect the presence of the virus. MATERIAL AND METHODS: A B19 antigen enzyme immunoassay (EIA) has been developed and the sensitivity of detection is ascertained using dilutions of the B19 capsid protein VP2 and 10 fold dilutions of B19 viraemic serum. Once the assay cut-off was established, a panel of viraemic donations (n = 70) was screened by the antigen EIA. The B19 immunoglobulin M (IgM) and IgG status of these specimens was also determined. During screening of blood donor units by quantitative PCR, 70 individuals were identified with levels of B19 DNA greater than 10(6) IU/ml at the time of blood donation. RESULTS: The sensitivity of the B19 antigen EIA was estimated to be equivalent to between 10(8) and 10(9) IU/ml B19 DNA or 1-10 pg/ml of recombinant capsid protein. B19 detection was significantly enhanced when viraemic specimens were pretreated with a low pH proprietary reagent. Unlike other virus-detection assays, detection of the B19 antigen was not affected by the presence of B19 IgM or IgG antibodies. In addition, the assay was capable of detecting all three genotypes of human erythrovirus. Combined specimen analysis by the B19 antigen assay and a B19 IgM assay facilitated the detection of 91% of acute B19 infections in the test population. CONCLUSION: In combination with B19 IgM detection, application of the B19 antigen EIA is a flexible and efficient method of detecting recent B19 infection and can be used as an alternative to PCR. PMID- 17845259 TI - Unexpected effects of donor gender on the storage of liquid plasma. AB - BACKGROUND: Swedish regulations in effect since 2006 allow the storage of plasma for transfusion up to 14 days at 2-6 degrees C and for 3 years at < or = -30 degrees C. In this study, the quality of currently used plasma components was investigated. MATERIALS AND METHODS: Plasma components, prepared from whole blood or by apheresis, either leucocyte depleted or not leucocyte depleted, were stored at 2-6 degrees C as liquid plasma or as thawed fresh-frozen plasma; 31% were from female donors. Concentration, function and activation markers of the plasma coagulation systems were investigated during storage for up to 42 days. RESULTS: Cold-induced contact activation was the dominant storage lesion, occurring earlier and at higher frequency in plasma from females. Increased kallikrein-like activity led to changes in activated partial thromboplastin time, prothrombin time, protein C and C1 inhibitor (C1INH). C1INH function dropped to 53% on Day 14 in cold-activated plasma components. CONCLUSION: Contact activation may be triggered before Day 14, especially in plasma from females, and may progress as a result of the consumption of C1INH. The data suggest that lack of cold-induced contact activation may be an important quality criterion. To achieve this, plasma from male donors could be selected for transfusion and the storage time limited to 7 days. PMID- 17845260 TI - Where and when is blood transfused? An observational study of the timing and location of red cell transfusions in the north of England. AB - BACKGROUND AND OBJECTIVES: This study was undertaken to provide denominator data relating to the timing and location of transfusion, to support interpretation of reports of incorrect blood component transfused (IBCT) events to the UK Serious Hazards of Transfusion (SHOT) scheme. MATERIALS AND METHODS: The study was carried out in 29 hospitals in northern England. Data on the timing, location and specialty responsible for transfusion were collected retrospectively (usually the following day) for all red cell units transfused over a 7-day period in September 2005. The timing and location of transfusion of these units was compared with those IBCT reports to SHOT between 1 January and 31 December 2005 in which there was an error in blood collection from the hospital storage site and/or administration to the patient. RESULTS: Data were received on 3123 red cell units, 3118 of which were analysable. Individual hospitals returned data on between 1 and 279 units. The data showed that 888 out of 3118 (28.5%) of units were transfused between 20:00 and 08:00 hours, while 63 out of 169 (37%) of IBCT reports to SHOT where there was an error in blood collection/administration were recorded as occurring during this time period. CONCLUSIONS: Comparison of our data with those from SHOT suggests that transfusions that are given outside core hours are more likely to be associated with clinical errors. PMID- 17845261 TI - Treatment of inherited protein C deficiency by replacement therapy with the French purified plasma-derived protein C concentrate (PROTEXEL). AB - BACKGROUND/OBJECTIVES: A multicentre retrospective study was performed to assess the efficacy/safety of a French purified plasma-derived protein C (PC) concentrate in inherited PC deficiency. MATERIALS AND METHODS: Nine patients were enrolled, five children aged < 5 weeks, among whom four with a severe deficiency were homozygous, and four patients < 37 years with PC levels ranging 14-25%, including one compound heterozygous. RESULTS: Thirty replacement therapy courses were recorded with mean PC dosages ranging between 24-90 IU/kg/day for prophylactic courses and 51-209 IU/kg/day for treatment courses. Recoveries varied between 0.8 and 1.12% IU/kg in preventive situations and between 1.09 and 1.91% IU/kg for treatment courses; 23 treatment courses were performed in patients aged 1 day to 18 years, 19 out of 23 treatments resulted in complete recovery with no sequelae. Treatment efficacy was difficult to assess in four out of 23 cases because the thrombotic event was not confirmed in one case and due to late treatment initiation in the three other cases. Seven prophylactic treatments were used either in association of vitamin K antagonists or to prevent thrombotic events due to vitamin K antagonist introduction or withdrawal. The safety assessed during 914 infusions was excellent. No abnormal bleeding was reported, including with high doses, during surgery, with heparin therapy. CONCLUSIONS: Replacement therapy with this French PC concentrate is safe and effective in patients with inherited PC deficiency. PMID- 17845262 TI - Incidence of transfusion-induced platelet-reactive antibodies evaluated by specific assays for the detection of human leucocyte antigen and human platelet antigen antibodies. AB - BACKGROUND AND OBJECTIVES: The aim of this work was to study the incidence of transfusion-induced platelet-reactive antibodies in a selective patient population and evaluate different methodologies for platelet antibody screening (PAS). MATERIALS AND METHODS: The patients were retrospectively selected and divided into three separate groups: haematological malignancies (Group 1: n = 33); cardiac and orthopaedic patients (Group 2: n = 31) and a control group (Group 3: n = 23) selected with the same diagnoses of Group 2. PRE- and POST transfusion samples were tested for PAS by the following tests: PIFT (platelet immunofluorescence test), MAIPA (monoclonal antibody immobilization of platelet antigen), Flow PRA(R) and LCT (lymphocytotoxicity test). RESULTS: There was not a 100% concordance among the methodologies used. PIFT, MAIPA and Flow PRA presented very similar results whereas that of LCT differed from the other methods. A high rate of positive results (32%) was found in the PRE samples followed by an increase of almost 50% after blood transfusion (POST samples: 42.5% of positivity), but there was a statistical difference (P < 0.05) between the PRE and POST transfusion sample only for the Flow PRA(R) technique tested on Group 2. Human leucocyte antigen (HLA) class I antibodies were present on 97.4% of POST positive samples, 5.4% presented anti-human platelet antigen (HPA)-1b antibodies and 8.1% presented a mix of pan-reactive antibodies against glycoprotein IIbIIIa, IaIIa and IbIX. CONCLUSIONS: Blood transfusion did not increase the rate of alloimmunization in our haematological patients (Group 1); however, the patients were already admitted with a high rate of alloimmunization (12%). Group 2 patients are being immunized and the impact of this procedure remains to be studied as these patients may eventually undergo further hospitalization and receive more blood transfusion. PMID- 17845263 TI - Donor recruitment research. PMID- 17845264 TI - Detection of bacterial contamination of platelet concentrates. PMID- 17845269 TI - Pharmacological interventions for acute bipolar mania: a systematic review of randomized placebo-controlled trials. AB - OBJECTIVES: We conducted a systematic review and meta-analysis of randomized, placebo-controlled trials in acute bipolar mania to summarize available data on drug treatment of mania. METHODS: We included trials of medications licensed in the USA or UK for the treatment of any phase of bipolar disorder. Outcomes investigated were changes in mania scores, attrition, extrapyramidal effects and weight change. Data were combined through meta-analyses. RESULTS: We included 13 studies (involving 3,089 subjects) and identified 2 studies for each of the following medications: carbamazepine, haloperidol, lithium, olanzapine, quetiapine, risperidone, valproate semisodium and aripiprazole. All drugs showed significant benefit compared with placebo for reduction in mania scores. Compared with placebo, for all antipsychotics pooled, response to treatment (> or =50% reduction in Young Mania Rating Scale scores) was increased more than 1.7 times [relative risk (RR) = 1.74, 95% confidence interval (CI) = 1.54, 1.96]; for all mood stabilizers pooled, response to treatment was doubled (RR 2.01, 95% CI = 1.66, 2.43). Overall withdrawals were 34% fewer (24-43%) with antipsychotics, and 26% fewer (10-39%) with mood stabilizers. However, for carbamazepine, aripiprazole and lithium an increase in risk of withdrawal could not be excluded. Small but significant increases in extrapyramidal side effects occurred with risperidone and aripiprazole. CONCLUSIONS: Antipsychotics and mood stabilizers are significantly more effective than placebo for the treatment of acute mania. Their effect sizes are similar. Small differences between effect sizes may be due to differences in the patients included in the studies or to chance. Carbamazepine and lithium may be more poorly tolerated, and antipsychotics cause more extrapyramidal side effects. PMID- 17845270 TI - Efficacy of a protein kinase C inhibitor (tamoxifen) in the treatment of acute mania: a pilot study. AB - OBJECTIVES: Considerable preclinical biochemical and behavioral data suggest that protein kinase C inhibition would bring about antimanic effects. Notably, the structurally highly dissimilar antimanic agents lithium and valproate, when administered in therapeutically relevant paradigms, attenuate protein kinase C [corrected] function. There is currently only one relatively selective protein kinase C inhibitor that crosses the blood-brain barrier available for human use- tamoxifen. Our group recently conducted a single-blind study with tamoxifen in acute mania and found that it significantly decreased manic symptoms within a short period of time (3-7 days). In this study, we investigated whether antimanic effects can be achieved with a protein kinase C inhibitor in subjects with mania. METHODS: In a double-blind, placebo-controlled study, 16 subjects with bipolar disorder, manic or mixed, with or without psychotic features, were randomly assigned to receive tamoxifen (20-140 mg/day; n = 8) or placebo (n = 8) for three weeks. Primary efficacy was assessed by the Young Mania Rating Scale. RESULTS: Subjects on tamoxifen showed significant improvement in mania compared to placebo as early as five days, an effect that remained significant throughout the three week trial. The effect size for the drug difference was very large (d = 1.08, 95% confidence interval 0.45-1.71) after three weeks (p = 0.001). At study endpoint, response rates were 63% for tamoxifen and 13% for placebo (p = 0.12). CONCLUSIONS: Antimanic effects resulted from a protein kinase C inhibitor; onset occurred within five days. Large, controlled studies with selective protein kinase C inhibitors in acute mania are warranted. PMID- 17845271 TI - The Bipolar Depression Rating Scale (BDRS): its development, validation and utility. AB - OBJECTIVES: Unipolar and bipolar depression differ neurobiologically and in clinical presentation. Existing depression rating instruments, used in bipolar depression, fail to capture the necessary phenomenological nuances, as they are based on and skewed towards the characteristics of unipolar depression. Both clinically and in research there is a growing need for a new observer-rated scale that is specifically designed to assess bipolar depression. METHODS: An instrument reflecting the characteristics of bipolar depression was drafted by the authors, and administered to 122 participants aged 18-65 (44 males and 78 females) with a diagnosis of DSM-IV bipolar disorder, who were currently experiencing symptoms of depression. The Bipolar Depression Rating Scale (BDRS) was administered together with the Hamilton Depression Rating Scale (HAM-D), Montgomery Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS). RESULTS: The BDRS has strong internal consistency (Cronbach's alpha = 0.917), and robust correlation coefficients with the MADRS (r = 0.906) and HAM-D (r = 0.744), and the mixed subscale correlated with the YMRS (r = 0.757). Exploratory factor analysis showed a three-factor solution gave the best account of the data. These factors corresponded to depression (somatic), depression (psychological) and mixed symptom clusters. CONCLUSIONS: This study provides evidence for the validity of the BDRS for the measurement of depression in bipolar disorder. These results suggest good internal validity, provisional evidence of inter-rater reliability and strong correlations with other depression rating scales. PMID- 17845272 TI - Genome-wide scan of bipolar II disorder. AB - OBJECTIVE: Bipolar disorder (BD) II is characterized by recurrent hypomanic and depressive episodes and has been somewhat of a controversial diagnosis since its description in the 1970s. Clinical opinions notwithstanding, the biological validity of BD II was supported in a genetic study of 58 multiplex bipolar families wherein the statistical evidence for linkage derived from BD II sibling pairs sharing marker alleles on chromosome 18q. The BD II phenotype alone has never been studied in a genome-wide scan analysis in the current or other bipolar family samples. We have performed genome-wide non-parametric analysis on 74 bipolar pedigrees using only the BD II phenotype as affection model. METHODS: This sample consists of the 65 pedigrees previously reported and 9 additional novel pedigrees that had BD II exclusively, as the affected phenotype. In the entire sample, there were 146 all possible relative-pairs. Analysis was performed using the non-parametric method in GENEHUNTER, with the 'ALL' option that computes linkage scores in all individuals in a pedigree simultaneously. RESULTS: The current analyses supported the previous finding on chromosome 18q21. In addition a peak with a non-parametric LOD (NPL) of 2.07 occurred between D9S915 and D9S2157, located on 9q34. Analysis of the nine BD II families alone identified peaks on 9p13 and 9q33, with NPL scores of 3.20 and 2.09, respectively. There was no evidence at 18q21 in these nine families. CONCLUSIONS: This suggests that there may be substantial differences in the etiology of BD in families that have BD II exclusively as the diagnosis. PMID- 17845273 TI - Coping styles in prodromes of bipolar mania. AB - OBJECTIVES: Psychological studies have identified that different coping strategies affect outcome in bipolar disorder (BD), with the possibility of preventing mania by effective coping with prodromes. This study seeks to examine coping mechanisms using a recently developed scale to clarify the relationship of coping styles to clinical and demographic characteristics, and to identify coping differences between bipolar I and II subjects. METHODS: The Coping Inventory for Prodromes of Mania (CIPM) was completed by 203 bipolar patients, along with other diagnostic and clinical measures. The CIPM is organized into four factors of coping including: stimulation reduction (SR), problem-oriented coping (PR), seeking professional help (SPH), denial and blame (DB). CIPM psychometric properties and its relationship to demographic and clinical factors, dysfunctional attitudes, and mood symptoms were examined. Coping profiles were generated by BD subtype (I versus II). RESULTS: The CIPM displayed psychometric properties consistent with the single previous study with this instrument. Neither demographic/clinical characteristics nor mood symptoms showed any particular relationship with the CIPM. Clear differences in coping also emerged between BD I and BD II subjects. BD I tended to use a wider range of coping strategies and scored highly on the SPH factor as compared to BD II subjects. BD II participants preferred to use DB and PR, but were less likely to use SPH and SR. CONCLUSIONS: The CIPM appears to be a valid measure of coping. Coping style preferences appear to differ according to bipolar subtype. PMID- 17845274 TI - Immune variations in bipolar disorder: phasic differences. AB - OBJECTIVES: To characterize the immunological variations of patients with a bipolar disorder (BD) diagnosis in manic (BDm) and depressive (BDd) phases, by the quantification of the serum levels of interleukin (IL)-1beta, -2, -4, -6 and tumor necrosis factor alpha (TNF-alpha). METHODS: Twenty physically healthy patients with a BD type I diagnosis and 33 matched controls were studied, after giving informed consent. The inclusion criteria included at least three weeks without any kind of psychopharmacological treatment, Young Mania Rating Scale score > or =20 for BDm (n = 10) and Hamilton Depression Rating Scale score > or =21 for BDd patients (n = 10). Exclusion criteria included any infectious diseases, allergies or any other kind of medical illness that required treatment with immunosuppressors, as well as any other diagnosis in Axis I. Physical and laboratory examinations were performed to rule out any clinical illness. Enzyme linked immunosorbent assay (ELISA) was used to analyze the serum cytokines concentration. RESULTS: BD patients, when compared to controls, showed significant differences (p < or = 0.05) in the serum levels of the measured cytokines. The sub-group of BDd patients showed an increase in IL-6 and TNF alpha, as well as a decrease in IL-2 concentration. The BDm sub-group, on the other hand, showed an increase in TNF-alpha and IL-4 values, with a low concentration of IL-1 and IL-2. The comparison between both sub-groups suggests that there is a distinctive cytokine pattern for the specific phases of the disorder: for mania, we found a high IL-4 and low IL-1beta and IL-6 concentration, while in the depressive phase, the inverse pattern was found. CONCLUSIONS: Our results show the existence of phasic differences in the serum levels of cytokines in BD. PMID- 17845275 TI - The impact of environmental temperature on lithium serum levels. AB - OBJECTIVES: Three studies have reported a seasonal variation in lithium serum levels, with higher levels during summer. Our objective was to investigate the impact of actual environmental temperature on lithium serum levels. METHODS: A retrospective study was conducted using available records of lithium serum levels for the period between January 1995 and July 2004, obtained from three large teaching hospitals in The Netherlands. Lithium serum levels were linked to season and average daily temperature data obtained from the Royal Netherlands Meteorological Institute. An analysis was performed on all lithium serum levels not accounting for the intra-individual dependency of lithium serum levels. The association between season, temperature and both absolute lithium serum level and the frequency of potentially toxic serum levels was investigated. A mixed model analysis, accounting for intra-individual dependency of lithium serum levels, was performed. RESULTS: A total of 41,102 lithium serum levels (3,054 patients) were included. A significant difference in mean lithium serum levels across seasons (p < 0.001) and temperature categories (p = 0.001) was found, peaking in summer [0.761 mmol/L, +/- standard error of the mean (SEM) 0.002] and at temperatures of 15-20 degrees C [0.762 mmol/L (+/- SEM 0.005)], and at a minimum in winter [0.748 mmol/L (+/- SEM 0.002)] and at <0 degrees C [0.741 mmol/L (+/- SEM 0.005)]. The relative frequency of potentially toxic serum levels significantly differed between seasons (p = 0.023, highest in winter), but not between temperature categories (p = 0.481). A significant positive association for intra-individual lithium serum level and season (p < 0.001) and temperature (p < 0.001) was established. CONCLUSIONS: Season and environmental temperature have a statistically significant but therapeutically irrelevant effect on lithium serum levels. PMID- 17845276 TI - A placebo-controlled, random-assignment, parallel-group pilot study of adjunctive topiramate for patients with schizoaffective disorder, bipolar type. AB - OBJECTIVES: This pilot study evaluated the efficacy and safety of adjunctive topiramate compared with placebo in the treatment of patients with a diagnosis of schizoaffective disorder, bipolar type (SAD-BT). METHODS: A sample of 48 adult patients with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) diagnosis of SAD-BT (supported by the Structured Clinical Interview for DSM-IV Axis I Disorder, Patient Edition) were randomly assigned in a 2:1 ratio (favoring topiramate) to 8 weeks of double-blind treatment with topiramate (100-400 mg/day) or placebo. Patients who had achieved a > or =20% decrease from baseline in their Positive and Negative Syndrome Scale (PANSS) total scores were given the opportunity to continue for an additional 8 weeks of double-blind treatment. The dosage of the study medicine was continued unchanged from the earlier 8-week study period. At the end of the study period, the study medicine was tapered and discontinued over a 2-week period. Primary efficacy was assessed at 8 weeks using the mean change between treatment groups of the PANSS total scores in the intent-to-treat population of randomized patients. Several secondary measures were also assessed. Safety analyses included monitoring of adverse events, vital signs, electrocardiogram (ECG) and laboratory values. RESULTS: Even though both treatments reduced scores on various psychopathology rating scales, adjunctive topiramate treatment (nearly 275 mg/day) did not show increased efficacy relative to placebo on the primary outcome measure (PANSS scale) or any of the secondary outcome measures. Topiramate-treated patients lost significantly more body weight than placebo treated patients, which led to a significant reduction in body mass index (BMI). Relative to adjunctive placebo, topiramate-treated patients experienced higher rates of paresthesia, sedation, word-finding difficulty, sleepiness, and forgetfulness, but these differences were not statistically significant. There were no clinically significant abnormalities in either the ECG or laboratory results. There were no serious adverse events in the study. Further, there was no worsening of the PANSS total scores (to > or =10% from baseline), and no significant differences between the treatments on worsening of total Montgomery Asberg Depression Rating Scale (MADRS) scores [1/13 (7.7%) for placebo; 1/25 (4.0%) for topiramate]. CONCLUSIONS: This pilot study did not support clinical efficacy for adjunctive topiramate treatment in patients with SAD-BT. There were no major safety or tolerability issues in this study. Confirming the results of other studies, topiramate-treated patients did experience greater body weight loss and reduction in BMI. PMID- 17845277 TI - Onset of antidepressant effect of olanzapine and olanzapine/fluoxetine combination in bipolar depression. AB - OBJECTIVES: The current analysis investigated the onset of antidepressant effect of olanzapine/fluoxetine combination. METHODS: Data for these post hoc analyses were obtained from a clinical trial comparing olanzapine, placebo, and olanzapine/fluoxetine combination in bipolar depression (BD). Subjects were 833 patients with a DSM-IV diagnosis of bipolar I disorder, depressed. The Montgomery Asberg Depression Rating Scale measured depressive symptoms. Multiple analytic methods were applied, including traditional (mean differences) analysis, pattern analysis, survival analysis of sustained response, mixed-effects regression, and area-under-the-curve analysis. RESULTS: Traditional analysis showed significantly greater improvement in depression scores at week 1 for olanzapine/fluoxetine combination versus placebo (-9.55 versus -5.08, p < 0.001) and for olanzapine versus placebo (-8.31 versus -5.08, p < 0.001). Pattern analysis revealed olanzapine/fluoxetine combination had a significantly greater percentage of early persistent responders than placebo or olanzapine (32.4% versus 12.7%, p < 0.001; and 18.3%, p < 0.05, respectively). Survival analysis showed a significantly shorter time to sustained response for the combination versus placebo (p < 0.001), for olanzapine versus placebo (p = 0.04), and for the combination versus olanzapine (p = 0.03). Mixed-effects regression analysis revealed a significant therapy-by-time interaction (p < 0.001). Early area-under-the-curve analysis revealed a significantly greater percentage of improvement for the combination versus placebo (26.7% versus 13.9%, p < 0.001) and for olanzapine versus placebo (22.0% versus 13.9%, p < 0.001). CONCLUSIONS: Based on consistent results from related methods of measuring onset, olanzapine/fluoxetine combination demonstrated rapid onset of antidepressant effect (within 7 days) compared to placebo that was sustained over 8 weeks of treatment in a sample of BD patients. Using multiple statistical techniques may help profile a drug's onset of effect. PMID- 17845278 TI - Agomelatine adjunctive therapy for acute bipolar depression: preliminary open data. AB - OBJECTIVES: Agomelatine has been shown to be safe and efficient in the treatment of major depressive disorder at 25 mg daily. The aim of this study was to gather preliminary data regarding the antidepressant efficacy of agomelatine in patients with bipolar I disorder experiencing a major depressive episode. METHODS: Bipolar I patients on lithium (n = 14) or valpromide (n = 7), with a Hamilton Rating Scale for Depression (HAM-D-17) total score > or = 18, were given adjunctive open label agomelatine at 25 mg/day for a minimum of 6 weeks followed by an optional extension of up to an additional 46 weeks. RESULTS: Using intent-to-treat data, 81% of patients met criteria for marked improvement (>50% improvement from baseline in HAM-D score) at study endpoint. Patients were severely depressed at study entry (HAM-D of 25.2) and 47.6% responded as early as at one week of treatment. Nineteen patients entered the optional extension period for a mean of 211 days (range 6-325 days). Eleven patients completed the one-year extension on agomelatine. There were no dropouts due to adverse events during the acute phase of treatment (6 weeks). Six patients experienced serious adverse events during the one-year period. Three lithium-treated patients experienced manic or hypomanic episodes during the optional extension period, one of which was treatment-related. CONCLUSIONS: These results indicate the effectiveness of agomelatine 25 mg in the treatment of depressed bipolar I patients co-medicated with lithium or valpromide. A randomized controlled trial is planned to confirm these results. PMID- 17845279 TI - Medication adherence skills training for middle-aged and elderly adults with bipolar disorder: development and pilot study. AB - OBJECTIVES: To present the rationale, development, and pilot study of a medication adherence skills training (MAST-BD) intervention for older adults with bipolar disorder (BPD). We developed a 12-week manualized group intervention that combined educational, motivational, medication management skills and symptom management training adapted for older adults. METHODS: Among 21 older outpatients with BPD (mean age = 60 years; SD = 6), the feasibility and acceptability of MAST BD were assessed in a quasi-experimental clinical trial. We also obtained preliminary effect sizes associated with pre-post change on measures of self reported adherence to psychiatric medications, performance-based medication management ability, attitudes toward medication, depressive and manic symptoms, and health-related quality of life. RESULTS: At baseline, 55% of participants reported recent non-adherence to psychiatric medications and were, on average, suffering from moderately severe depressive symptoms and minimal symptoms of mania. A total of 76% of participants completed the intervention, and 86% of sessions were attended by completers. Participants reported high levels of satisfaction with the intervention and manual. Pre-post improvement by small to medium effect sizes (Cohen's d = 0.30-0.57) was seen in medication adherence, medication management ability, depressive symptoms, and selected indices of health-related quality of life. CONCLUSIONS: Notwithstanding the limitations of this small preliminary study, the results are encouraging in that the MAST-BD intervention was feasible, acceptable to patients, and associated with improvement in key outcomes. Suggestions for further development of medication adherence interventions for this neglected group of patients are discussed. PMID- 17845280 TI - Is bipolar disorder overdiagnosed among patients with substance abuse? AB - BACKGROUND: Bipolar illness is frequently misdiagnosed. Several studies have focused on the underdiagnosis of this condition and the frequent long delay in its recognition. However, the illness is difficult to diagnose and many of its symptoms are shared by other conditions. In order to determine the accuracy of the diagnosis of bipolar illness among subjects with substance abuse, we carried out a study in patients with a previous diagnosis of bipolar disorder (BD) and known history of substance abuse or dependence, who were currently engaged in treatment for substance abuse. METHODS: Individuals participating in a community based substance treatment program and who had a previous diagnosis of BD were invited to undergo a structured clinical interview for diagnosis performed by a psychiatrist. In addition to the interview, previous hospital records were reviewed whenever possible. Diagnosis was made following strict DSM-IV criteria. RESULTS: Only 9 of 21 (42.9%) subjects met diagnostic criteria for BD. Seven were BD type II and two were BD I. CONCLUSIONS: Bipolar disorder is frequently misdiagnosed following strict DSM-IV criteria. Among subjects with substance abuse, it may be overdiagnosed by psychiatrists. PMID- 17845281 TI - Post-traumatic stress disorder among adolescents with bipolar disorder and its relationship to suicidality. AB - OBJECTIVES: The aims of this cross-sectional pilot study were to ascertain the rates of post-traumatic stress disorder (PTSD) among adolescents with bipolar disorder (BPD) and major depressive disorder (MDD) relative to a comparison group comprised of non-affectively ill patients, and to determine whether PTSD is related to suicidal ideation and attempts. The impetus for the study was born of clinical impressions derived in the course of routine clinical practice. METHODS: Patients were screened by a single interviewer for BPD, MDD and PTSD, panic disorder, obsessive-compulsive disorder (OCD) and social phobia using the apposite modules from the Structured Clinical Interview for DSM-IV (SCID) and histories of suicidal ideation and attempts. The data were subjected to analysis using a logistic regression model. RESULTS: The database included 34 patients with BPD, 79 with MDD and 26 with a non-affective disorder. The risk for PTSD for a patient with BPD significantly exceeded that for a patient with MDD [odds ratio (OR) = 4.9, 95% confidence interval (CI) = 1.9-12.2, p = 0.001]. Patients with PTSD had an insignificantly increased risk for suicidal ideation (OR = 2.8, 95% CI = 0.9-8.9, p = 0.069), and a 4.5-fold significantly increased risk of having had a suicide attempt (OR = 4.5, 95% CI = 1.7-11.7, p = 0.002). The relationship between PTSD and suicide attempts remained significant even after controlling for the confounding effects of concurrent panic disorder, OCD and social phobia (OR = 3.4, 95% CI = 1.1-10.0, p = 0.023). CONCLUSIONS: Patients with BPD have a greater risk for PTSD than those with MDD. Post-traumatic stress disorder is significantly related to history of suicide attempts. PMID- 17845282 TI - Adherence to medication in bipolar disorder: a qualitative study exploring the role of patients' beliefs about the condition and its treatment. AB - OBJECTIVES: Patients' perceptions of illness and treatment have been found to predict adherence to medication in many chronic conditions. This has not yet been fully explored in bipolar disorder (BD). The aim was to use a qualitative methodology to explore in depth the beliefs about BD and its treatment that are associated with adherence to medication prescribed for BD. METHODS: Sixteen adults prescribed prophylactic treatment for BD completed semi-structured interviews about their perceptions of BD and its treatment and their adherence to medication. Interviews were recorded and transcribed verbatim. Two researchers identified perceptions associated with non-adherence in the transcripts. RESULTS: Thirteen participants (81%) reported some degree of intentional or unintentional medication non-adherence. Intentional non-adherence was associated with patients' concerns about the prescribed medication, arising from the experience of side effects, but also from beliefs that regular use could lead to adverse effects in the future. Intentional non-adherence was also associated with doubts about the personal need for medication, which were related to perceptions of BD (e.g., not accepting diagnosis, believing the condition is not controllable, believing it is not a chronic condition). CONCLUSIONS: This study has identified some of the salient beliefs about BD and its treatment that should be elicited and addressed in interventions to facilitate adherence to medication. Further quantitative work is justified to explore the utility of this approach in the development of interventions. PMID- 17845283 TI - Cotard's syndrome in adolescents and young adults is associated with an increased risk of bipolar disorder. AB - OBJECTIVES: To assess the effect of age at onset on the phenomenology of Cotard's syndrome (CS) as a recent study reported a high rate of occurrence of bipolar disorder (BD) in adolescents and young adults with CS followed up for > or =2 years. METHODS: We reviewed all cases of CS reported since it was first described. A statistical analysis was carried out to determine the effect of age at onset on CS phenomenology. RESULTS: We found 138 cases including 21 cases aged 25 years or younger. In these younger CS patients, BD was more frequent, and the risk of associated BD was increased nine times (p < 0.0001). Within the BD sub group (n = 27), admixture analysis identified two sub-groups with mean ages at onset of 18.7 years [standard deviation (SD) = 3.2] and 50.5 years (SD = 11.7). CONCLUSIONS: Young people with CS should be monitored carefully for the onset of BD, and families should be educated about this risk. Treatment with mood stabilizers can be helpful for those who develop BD. Within BD associated with CS, early versus late onset should be distinguished. PMID- 17845284 TI - Chromosome 9 and the genetics of bipolar I disorder. PMID- 17845285 TI - Lifespan is unrelated to investment in reproduction in populations of mammals and birds in captivity. AB - We examined the relationship between number of offspring produced to a certain age and subsequent longevity in captive zoo populations of 18 species of mammal and 12 species of bird. The age cut-offs in each analysis were set to include 50%, 75% and 90% of the offspring produced in each of the population samples. Only one of 68 regressions was significant, and its slope was positive. In addition, we examined the relationship between age at first reproduction up to a certain age and longevity after that age, generally 5 years (3-8), among 17 species of mammal and 12 species of bird. Only one of these regressions had a significantly positive slope, indicating that early reproduction rarely reduces lifespan. Overall, we found no evidence that producing offspring in a zoo environment influences the age at death. Thus, although trade-offs might apply in natural populations under resource limitation, neither pregnancy, growth of the foetus and lactation in mammals, nor egg production in birds, reduces lifespan in the absence of such stress. If genetically based or other intrinsic antagonistic pleiotropy underlies the evolution of senescence, it was not evident in our analyses. PMID- 17845286 TI - Commentary on Ricklefs & Cadena (2007): Reproductive investment and lifespan. PMID- 17845288 TI - Applying population-genetic models in theoretical evolutionary epidemiology. AB - Much of the existing theory for the evolutionary biology of infectious diseases uses an invasion analysis approach. In this Ideas and Perspectives article, we suggest that techniques from theoretical population genetics can also be profitably used to study the evolutionary epidemiology of infectious diseases. We highlight four ways in which population-genetic models provide benefits beyond those provided by most invasion analyses: (i) they can make predictions about the rate of pathogen evolution; (ii) they explicitly draw out the mechanistic way in which the epidemiological dynamics feed into evolutionary change, and thereby provide new insights into pathogen evolution; (iii) they can make predictions about the evolutionary consequences of non-equilibrium epidemiological dynamics; (iv) they can readily incorporate the effects of multiple host dynamics, and thereby account for phenomena such as immunological history and/or host co evolution. PMID- 17845289 TI - Growth-size scaling relationships of woody plant species differ from predictions of the Metabolic Ecology Model. AB - The Metabolic Ecology Model predicts that tree diameter (D) growth (dD/dt) scales with D(1/3). Using data on diameter growth and height-diameter relationships for 56 and 40 woody species, respectively, from forests throughout New Zealand, we tested one prediction and two assumptions of this model: (i) the exponent of the growth-diameter scaling relationship equals 1/3 and is invariant among species and growth forms, (ii) small and large individuals are invariant in their exponents and (iii) tree height scales with D(2/3). We found virtually no support for any prediction or assumption: growth-diameter scaling exponents varied substantially among species and growth forms, correlated positively with species' maximum height, and shifted significantly with increasing individual size. Tree height did not scale invariantly with diameter. Based on a quantitative test, violation of these assumptions alone could not explain the model's poor fit to our data, possibly reflecting multiple, unsound assumptions, as well as unaccounted-for variation that should be incorporated. PMID- 17845290 TI - Ecosystem engineers activate mycorrhizal mutualism in salt marshes. AB - Theory predicts that ecosystem engineers should have their most dramatic effects when they enable species, through habitat amelioration, to live in zones where physical and biological conditions would otherwise suppress or limit them. Mutualisms between mycorrhizal fungi and plants are key determinants of productivity and biodiversity in most terrestrial systems, but are thought to be unimportant in wetlands because anoxic sediments exclude fungal symbionts. Our field surveys revealed arbuscular mycorrhizal associations on salt marsh plant roots, but only in the presence of crabs that oxygenate soils as a by-product of burrowing. Field experiments demonstrate that fungal colonization is dependent on crab burrowing and responsible for nearly 35% of plant growth. These results highlight ecosystem engineers as ecological linchpins that can activate and maintain key mutualisms between species. Our findings align salt marshes with other important biogenic habitats whose productivity is reliant on mutualisms between the primary foundation species and micro-organisms. PMID- 17845291 TI - Apparent climatically induced increase of tree mortality rates in a temperate forest. AB - We provide a first detailed analysis of long-term, annual-resolution demographic trends in a temperate forest. After tracking the fates of 21,338 trees in a network of old-growth forest plots in the Sierra Nevada of California, we found that mortality rate, but not the recruitment rate, increased significantly over the 22 years of measurement (1983-2004). Mortality rates increased in both of two dominant taxonomic groups (Abies and Pinus) and in different forest types (different elevational zones). The increase in overall mortality rate resulted from an increase in tree deaths attributed to stress and biotic causes, and coincided with a temperature-driven increase in an index of drought. Our findings suggest that these forests (and by implication, other water-limited forests) may be sensitive to temperature-driven drought stress, and may be poised for die-back if future climates continue to feature rising temperatures without compensating increases in precipitation. PMID- 17845292 TI - Separating the determinants of phylogenetic community structure. AB - The role of competition in forbidding similar species from co-occurring has long been debated. A difficulty in identifying this repulsion of similar species is that similar species share similar environmental requirements and hence show an attraction to communities where these requirements are met. To disentangle these opposing patterns, we use phylogenetic relatedness as an objective metric of species similarities. Studying 11 sunfishes (Centrarchidae) from 890 lakes, we first show no phylogenetic pattern in the raw community data. We then regressed sunfish presence/absence against seven environmental variables and show that lakes with similar water clarity and latitude likely contain closely related species. After statistically removing the environmental effects, phylogenetic repulsion was apparent, with closely related sunfishes less likely to co-occur. Thus, both phylogenetic attraction, driven by environmental filtering, and phylogenetic repulsion, possibly caused by competition, simultaneously occur and obscure one another in the overall phylogenetic structure of sunfish communities. PMID- 17845293 TI - Simultaneous feeding by aboveground and belowground herbivores attenuates plant mediated attraction of their respective natural enemies. AB - Herbivore-damaged plants emit volatile organic compounds that attract natural enemies of the herbivores. This form of indirect plant defence occurs aboveground as well as belowground, but it remains unclear how simultaneous feeding by different herbivores attacking leaves and roots may affect the production of the respective defence signals. We employed a setup that combines trapping of volatile organic signals and simultaneous measurements of the attractiveness of these signals to above and belowground natural enemies. Young maize plants were infested with either the foliar herbivore Spodoptera littoralis, the root herbivore Diabrotica virgifera virgifera, or with both these important pest insects. The parasitic wasp Cotesia marginiventris and the entomopathogenic nematode Heterorhabditis megidis were strongly attracted if their respective host was feeding on a plant, but this attraction was significantly reduced if both herbivores were on a plant. The emission of the principal root attractant was indeed reduced due to double infestation, but this was not evident for the leaf volatiles. The parasitoid showed an ability to learn the differences in odour emissions and increased its response to the odour of a doubly infested plant after experiencing this odour during an encounter with hosts. This first study to measure effects of belowground herbivory on aboveground tritrophic signalling and vice-versa reemphasizes the important role of plants in bridging interactions between spatially distinct components of the ecosystem. PMID- 17845294 TI - Niche width collapse in a resilient top predator following ecosystem fragmentation. AB - Much research has focused on identifying species that are susceptible to extinction following ecosystem fragmentation, yet even those species that persist in fragmented habitats may have fundamentally different ecological roles than conspecifics in unimpacted areas. Shifts in trophic role induced by fragmentation, especially of abundant top predators, could have transcendent impacts on food web architecture and stability, as well as ecosystem function. Here we use a novel measure of trophic niche width, based on stable isotope ratios, to assess effects of aquatic ecosystem fragmentation on trophic ecology of a resilient, dominant, top predator. We demonstrate collapse in trophic niche width of the predator in fragmented systems, a phenomenon related to significant reductions in diversity of potential prey taxa. Collapsed niche width reflects a homogenization of energy flow pathways to top predators, likely serving to destabilize remnant food webs and render apparently resilient top predators more susceptible to extinction through time. PMID- 17845295 TI - Mass regulation in response to predation risk can indicate population declines. AB - In theory, survival rates and consequent population status might be predictable from instantaneous behavioural measures of how animals prioritize foraging vs. avoiding predation. We show, for the 30 most common small bird species ringed in the UK, that one quarter respond to higher predation risk as if it is mass dependent and lose mass. Half respond to predation risk as if it only interrupts their foraging and gain mass thus avoiding consequent increased starvation risk from reduced foraging time. These mass responses to higher predation risk are correlated with population and conservation status both within and between species (and independently of foraging habitat, foraging guild, sociality index and size) over the last 30 years in Britain, with mass loss being associated with declining populations and mass gain with increasing populations. If individuals show an interrupted foraging response to higher predation risk, they are likely to be experiencing a high quality foraging environment that should lead to higher survival. Whereas individuals that show a mass-dependent foraging response are likely to be in lower quality foraging environments, leading to relatively lower survival. PMID- 17845296 TI - Long-term reproductive behaviour of woody plants across seven Bornean forest types in the Gunung Palung National Park (Indonesia): suprannual synchrony, temporal productivity and fruiting diversity. AB - For 68 months, we observed the reproductive behaviour of 7288 woody plants (172 figs, 1457 climbers and 5659 trees) spanning major soil and elevational gradients. Two 2-3 month community-wide supra-annual fruiting events were synchronized across five forest types, coinciding with ENSO events. At least 27 genera in 24 families restricted their reproduction to these events, which involved a substantial proportion of tree diversity (> 80% of phylogenetic diversity). During these events, mean reproductive levels (8.5%) represented an almost four-fold increase compared with other months. These patterns indicate a strong behavioural advantage to this unusual reproductive behaviour. Montane forest experienced a single, separate fruiting peak while the peat swamp forest did not participate. Excluding these events, no temporal reproductive pattern was detectable, at either the landscape or forest type. These phenological patterns have major implications for the conservation of frugivore communities, with montane and swamp forests acting as 'keystone' forests. PMID- 17845297 TI - On the stability of populations of mammals, birds, fish and insects. AB - A key concern for conservation biologists is whether populations of plants and animals are likely to fluctuate widely in number or remain relatively stable around some steady-state value. In our study of 634 populations of mammals, birds, fish and insects, we find that most can be expected to remain stable despite year to year fluctuations caused by environmental factors. Mean return rates were generally around one but were higher in insects (1.09 +/- 0.02 SE) and declined with body size in mammals. In general, this is good news for conservation, as stable populations are less likely to go extinct. However, the lower return rates of the large mammals may make them more vulnerable to extinction. Our estimates of return rates were generally well below the threshold for chaos, which makes it unlikely that chaotic dynamics occur in natural populations--one of ecology's key unanswered questions. PMID- 17845298 TI - Species abundance distributions: moving beyond single prediction theories to integration within an ecological framework. AB - Species abundance distributions (SADs) follow one of ecology's oldest and most universal laws--every community shows a hollow curve or hyperbolic shape on a histogram with many rare species and just a few common species. Here, we review theoretical, empirical and statistical developments in the study of SADs. Several key points emerge. (i) Literally dozens of models have been proposed to explain the hollow curve. Unfortunately, very few models are ever rejected, primarily because few theories make any predictions beyond the hollow-curve SAD itself. (ii) Interesting work has been performed both empirically and theoretically, which goes beyond the hollow-curve prediction to provide a rich variety of information about how SADs behave. These include the study of SADs along environmental gradients and theories that integrate SADs with other biodiversity patterns. Central to this body of work is an effort to move beyond treating the SAD in isolation and to integrate the SAD into its ecological context to enable making many predictions. (iii) Moving forward will entail understanding how sampling and scale affect SADs and developing statistical tools for describing and comparing SADs. We are optimistic that SADs can provide significant insights into basic and applied ecological science. PMID- 17845299 TI - HLA analysis of Sri Lankan Sinhalese predicts North Indian origin. AB - The origin of the Sinhalese population of Sri Lanka is debated. We subtyped HLA A*02 in 101 Sinhalese and observed a preponderance of the rare allele HLA-A*0211 which was similar to reported frequencies in northern India. Taken with low resolution typing for the remaining A, B, C, DR and DQ alleles, these data suggest a North Indian origin for the Sri Lankan Sinhalese. PMID- 17845300 TI - Promoter polymorphism of IL-18 gene in pulmonary tuberculosis in South Indian population. AB - Interleukin-18 (IL-18) plays a vital role in both innate and acquired immunity. We analysed polymorphisms at -607(C/A) and -137(G/A) in the promoter region of IL 18 gene by allele-specific polymerase chain reaction in normal healthy subjects (n = 173) and patients with pulmonary tuberculosis (n = 165). Allele, genotype and haplotype frequencies did not differ significantly between normal healthy subjects and patients. The results suggest that the IL-18 gene promoter polymorphisms are not associated with susceptibility or resistance to pulmonary tuberculosis in south Indian population of Dravidian descent. PMID- 17845301 TI - Extensive gene conversion between CCR2 and CCR5 in domestic cat (Felis catus). AB - Homogenization of the CC-motif chemokine receptors CCR2 and CCR5 of cat (Felis catus) is documented and shown to be the outcome of gene conversion within the feline lineage. All regions were concerned, except the three extracellular protein domains (N- and C-tails, and ECL2), suggesting that structural differentiation at these domains could be related to pathogen susceptibility. PMID- 17845302 TI - Polymorphisms in CCR5 chemokine receptor gene in Japan. AB - Mutations in the human CC chemokine receptor 5 (CCR5) gene may alter the expression or function of the protein product, thereby altering chemokine binding/signalling or human immunodeficiency virus type 1 (HIV-1) infection of the cells that normally express CCR5 protein. We performed a systematic survey of natural sequence variations in an 8.1-kb region of the entire CCR5 gene as well as CCR2V64I in 50 Japanese subjects and evaluated the effects of those variations on CCR5 promoter activity. We also analysed CCR5 promoters and CCR2V64I in 80 more Japanese and 186 Thais. There was no 32-bp deletion observed in Caucasians, but two types of non-synonymous substitutions were found in CCR5 genes of Japanese. Our results showed several novel characteristics of the CCR2-CCR5 haplotype structure that were not reported from studies on Caucasians and African Americans. Specifically, we were able to show that the G allele at position -2852 from the CCR5 open reading frame in Japanese and Thais is the representative of the CCR5 promoter haplotype that was reported to be associated with rapid progression to acquired immune deficiency syndrome (AIDS) in HIV-1-infected individuals. Furthermore, nearly all non-synonymous polymorphisms in Japanese CCR5 occurred in haplotypes with elevated promoter activity. We thus hypothesized that there was a certain selective pressure favouring low levels of CCR5 expression during human evolution. PMID- 17845303 TI - Application of the particle gel agglutination system as a new check gel assay for PCR products. AB - In this study, we describe a simple and rapid agglutination test for the detection of PCR products prior to the application of specific hybridization by sequence-specific oligonucleotide typing. This test is based on the particle gel agglutination immunoassay, incorporating biotinylated primers and streptavidin particles. Visually detectable agglutination was only observed in samples which contained the specific amplification products. The results obtained by the new test were in accordance with those obtained by standard gel electrophoresis in all cases that have been tested to date. PMID- 17845304 TI - Influences of MxA gene -88 G/T and IFN-gamma +874 A/T on the natural history of hepatitis B virus infection in an endemic area. AB - The influence of human genetics on the natural history of hepatitis B virus (HBV) infection may be diminished in endemic areas because infection at a young age predisposes to chronic HBV infection. The present study aimed to address this issue through the determination of the influences of single nucleotide polymorphisms (SNPs) of myxovirus resistence-1 (MxA) -88 G/T and interferon (IFN) gamma +874 A/T on the natural history of HBV infection in endemic regions. One hundred adult patients with self-limiting HBV infection (positive for both anti HBs and anti-HBc) and 340 adult patients with persistent HBV infection were recruited from southern China, an endemic area with an HBsAg carrier rate of 17.8%. SNPs of MxA -88 G/T and interferon (IFN)-gamma +874 A/T were typed using a protocol based on competitively differentiated polymerase chain reaction. A highly significant difference in the distribution of MxA -88 G/T was observed between those with persistent and self-limiting HBV infections. The latter displayed a lower frequency of the GG genotype (41.0% vs. 52.9%, P = 0.036) and a higher frequency of the TT genotype (16.0% vs. 2.4%, P = 0.000), compared to patients with persistent infection. These differences were not gender- or age specific. However, a significant distribution difference of IFN-gamma +874 A/T was not observed. Between two groups of patients, respectively, the distribution frequencies of the AA genotype (65.0% vs. 72.8%, P = 0.139) and the TT genotype (2.0% vs. 1.2%, P = 0.894) were found. These results suggest that MxA gene -88 G/T and IFN-gamma +874 A/T behave differently in endemic HBV infections. Further study is necessary to clarify the influences of human genetics on endemic HBV infections. PMID- 17845305 TI - Localization of Per a 3 allergen in the gut and faecal pellets of the American cockroach (Periplaneta americana). AB - Cockroach-derived materials are known to be a major source of potent aeroallergens, causing allergic respiratory diseases such as asthma and allergic rhinitis. The aim of this study was to determine the localization of the major allergen, Per a 3 (Cr-PI), within the American cockroach (Periplaneta americana), which might reveal the relative importance of excreted materials and nonexcreted cockroach components as allergen sources. American cockroaches (P. americana) and their faecal pellets were embedded in paraffin, and serial sections were cut and collected on glass slides. After being stained with mouse polyclonal antiserum against Per a 3, the sections were incubated sequentially with biotin-labelled sheep antimouse immunoglobulin G (IgG) and a preformed fluorescent isothiocyanate (FITC)-avidin complex. Finally, the sections were mounted and examined under a fluorescent microscope. Examination of Per a 3 immunoreactivity on the sections of the American cockroaches (P. americana) revealed that the midgut mucosa, gut contents and faecal pellets were all strongly labelled. Per a 3 immunoreactive products were not detected in any other internal organs of the American cockroaches. These results suggest that Per a 3 allergen might be synthesized in and secreted from the epithelia of the midgut mucosa and excreted from the body in the faecal pellets. PMID- 17845306 TI - Lack of association between three promoter polymorphisms of PTGDR gene and asthma in a Chinese Han population. AB - The PTGDR gene has been suggested to be an asthma susceptibility gene in previous genome-wide linkage studies as well as in functional studies in a mouse model of asthma. Recently, promoter polymorphisms of the PTGDR gene have been reported to be associated with asthma in American and European populations. In order to determine the association of PTGDR promoter polymorphisms and asthma susceptibility in a Chinese Han population, three promoter single nucleotide polymorphisms (SNP) -549T/C, -441C/T, and -197T/C were genotyped in 336 patients with asthma and 264 healthy controls. Asthma was diagnosed according to the American Thoracic Society (ATS) criteria. SNPs -549T/C and -441C/T were genotyped by Tetra-primer Amplification Refractory Mutation System PCR method and -197T/C by polymerase chain reaction-restriction fragment length polymorphism method. Unlike the results observed in American and European populations, none of the three SNPs nor any haplotypes in the PTGDR promoter region were found to be associated with asthma susceptibility in this Chinese Han population (all P-value > 0.05). The frequencies for both high-transcriptional-efficiency haplotype (CCC) and low-transcriptional-efficiency haplotype (TCT) were lower than 1% in patients and controls, significantly different from those observed in American and European populations. These results suggest that the three PTGDR gene promoter polymorphisms studied are not important risk factors for asthma susceptibility in the Chinese Han population. PMID- 17845307 TI - A putative gene located at the MHC class I region around the D6S105 marker contributes to the setting of CD8+ T-lymphocyte numbers in humans. AB - Significant associations between human leucocyte antigen (HLA)-A and -B alleles and CD8+ T-lymphocyte numbers have been reported in the literature in both healthy populations and in HFE-haemochromatosis patients. In order to address whether HLA alleles themselves or alleles at linked genes are responsible for these associations, several genetic markers at the MHC class I region were typed on a population of 147 apparently healthy unrelated subjects phenotypically characterized for their CD8+ and CD4+ T-lymphocyte numbers. By using a machine learning approach, a set of rules was generated that predict the number of CD8+ T lymphocyte numbers on the basis of the information of the D6S105 microsatellite alleles only. We demonstrate that the previously reported associations with HLA-A and -B alleles are due to the presence of common long (up to 4 megabases long) haplotypes that increased in frequency recently due to positive selection and that encompass a region where a putative gene contributing to the setting of CD8+ T lymphocytes is located, in the neighbourhood of microsatellite locus D6S105, in the 6p21.3 region. PMID- 17845308 TI - The FcgammaRIIa polymorphism influences production of interleukin-1 by mononuclear cells. AB - The functional bi-allelic polymorphism of immunoglobulin G (IgG) Fc receptor (FcgammaR) IIa influences the efficiency of human IgG2 binding. Our previous study showed that the high affinity FcgammaRIIa genotype (-H/H131) was associated with periodontitis risk. As interleukin-1 (IL-1) is one of the major causes of periodontal tissue destruction, it is hypothesized that the FcgammaRIIa H/H131cross-linking could induce an increased IL-1 release by mononuclear cells. In this study, we evaluated the intracellular expressions of IL-1beta in CD14 positive cells upon stimulation with human IgG2 by flow cytometry. FcgammaRIIa H/H131 subjects exhibited a higher percentage of IL-1beta-producing cells than FcgammaRIIa-R/H131 and -R/R131 subjects (P < 0.05). These results support the concept that FcgammaRIIa genotype may affect IL-1beta production, possibly leading to interindividual differences in periodontitis risk. PMID- 17845309 TI - Association of polymorphisms of human leucocyte antigen-DQA1 and DQB1 alleles with chronic hepatitis B virus infection, liver cirrhosis and hepatocellular carcinoma in Chinese. AB - To investigate whether human leucocyte antigen (HLA) class II DQA1 and DQB1 gene polymorphisms are associated with chronic hepatitis B virus (HBV) infection and development of HBV-related liver cirrhosis (LC) and hepatocellular carcinoma (HCC), we detected the DQA1 and DQB1 allele polymorphisms in 168 HBV carriers (including 48 chronic hepatitis B, 42 LC and 78 HCC patients) and 100 controls who had recovered from HBV infection by using polymerase chain reaction amplification with sequence-specific primers (PCR-SSP). Our data suggest that DQA1*0102 and DQA1*0104 were associated with protection from chronic HBV infection (P(c) = 0.003) and development of LC (P(c) = 0.001), respectively, whereas DQB1*0201 conferred susceptible effect on chronic HBV infection (P(c) = 0.008). We also found that DQA1*0601, DQB1*0601 and DQA1*0201 showed some susceptible effect on chronic HBV infection and LC, respectively, however, these associations were no longer significant after Bonferroni correction (P(c) = 0.390, P(c) = 0.475 and P(c) = 0.140, respectively). No significant association has been found between DQA1 and DQB1 alleles and development of HCC. These results indicate that different subtypes of HLA-DQA1 and DQB1 are associated with development of chronic HBV infection and LC, respectively, in Han Chinese population. PMID- 17845310 TI - Influence of HLA-DR2 on perforin-positive cells in pulmonary tuberculosis. AB - Perforin is one of the key effector molecules of cytotoxic T cells and natural killer cells. The influence of HLA-DRB1 alleles on peripheral blood perforin positive CD4, CD8, CD16 and CD 56 cells was studied by flow cytometry. HLA-DRB1 typing was done in normal healthy subjects (NHS: n = 156) and patients with pulmonary tuberculosis (PTB: n = 102) by polymerase chain reaction-based sequence specific oligonucleotide hybridization method. We observed a significantly decreased percentage of total perforin-positive cells (per(+)) (P = 0.0004); CD8(+)/Per(+) (P = 0.0005); CD16(+)/Per(+) (P = 0.05) and CD 56(+)/Per(+) cells (P = 0.001) in HLA-DR2-positive PTB patients compared to non-DR2 patients. Subtyping of HLA-DR2-positive subjects at the allelic level revealed that the percentage of CD8(+)/Per(+) cells did not differ among DRB1*1501 and DRB1*1502 patients while a trend towards a decreased percentage of CD16(+)/Per(+) and CD 56(+)/Per(+) cells was noticed in DRB1*1501 patients compared to DRB1*1502 patients. The present study suggests that HLA-DR2 may be associated with down regulation of perforin-positive cytotoxic lymphocytes and natural killer cells in pulmonary tuberculosis. PMID- 17845311 TI - Determination of HLA-A, -B and -DRB1 haplotypes based on allelic homozygosity data in selected bone marrow donors of the Taiwanese marrow donor registry. AB - From 120 unrelated Taiwanese marrow stem cell donors with allelic homozygosities at human leucocyte antigen (HLA)-A, -B and -DRB1 loci, we determined 85 distinguishable haplotypes. Using the predetermined haplotype data, we deduced 418 haplotypes from 1903 unrelated individual stem cell donors selected for HLA confirmatory test. Eighteen of the 20 (90%) most frequently observed haplotypes determined in Asian Americans using computer prediction were found in this study. In comparison with haplotypes determined by maximum likelihood algorithm in Korean population, 18 of the 29 (62.07%) Korean haplotypes with a frequency over 0.5% were also among the haplotypes determined in this investigation. Randomized family studies confirmed that over 50% of the haplotypes observed in the families were among the haplotypes deduced based on allelic homozygosity, suggesting that proportionally additional haplotypes can be determined as the number of donors being studied is increased. Haplotypes carrying low incidence allele characteristics of Taiwanese were also observed in this study. This established haplotype information will be beneficial for patients searching for stem cell donors in our registry domestically and internationally. PMID- 17845315 TI - Three-dimensional sonographic volume measurement of the fetal spleen. AB - AIM: The objective of this longitudinal study was to evaluate the growth of the fetal spleen in normal pregnancies, using three-dimensional ultrasound. METHODS: Three-dimensional sonographic examinations were performed on 14 appropriate-for gestational-age fetuses. Fetal splenic volume was measured every 2-3 weeks after 20 weeks of gestational age until delivery. RESULTS: Curvilinear relationships were found between the gestational age and splenic volume (R(2) = 80.2%, P < 0.0001), and normal ranges of splenic volume measurements for estimating the growth of the fetal spleen during normal pregnancy were generated. We found that the splenic volume calculation based on the equation for the volume of the ellipsoid by conventional two-dimensional ultrasound in previous investigations is about twice as large as that using three-dimensional ultrasound in our study, whereas the present data described in this study is quite comparable with previous data from an autopsy series. CONCLUSION: Our findings suggest that the standard curve for the fetal splenic volume using three-dimensional ultrasound provides a superior means for evaluating the normal splenic growth in the fetus and for identifying splenic abnormalities in utero. However, the data and its interpretation in our study should be taken with some degree of caution because of the small number of subjects studied. Further studies involving a larger sample size would be needed to confirm these findings. PMID- 17845316 TI - Placenta previa increta/percreta in Japan: a retrospective study of ultrasound findings, management and clinical course. AB - AIM: Placenta accreta is an abnormally firm attachment of placental villi to the uterine wall, which may cause postpartum hemorrhage resulting in maternal morbidity and mortality. The purpose of the present study was to clarify the incidence, clinical background and prognosis of placenta previa increta/percreta treated with different modalities in Japan. METHODS: Medical records of cases with placenta previa increta/percreta in eight tertiary centers between January 1994 and December 2004 were reviewed. Placenta accreta without actual invasion into the myometrium confirmed by pathology was not included in placenta increta/percreta. Details of obstetric history, maternal background, ultrasonographical findings, the course of delivery, subsequent complications and management were noted. RESULTS: Among the total of 59,008 deliveries, 45,261 were by the vaginal route (76.7%) and 13 747 by cesarean section (23.3%). In this study, 408 cases were diagnosed as placenta previa (0.69%), 18 of these being placenta increta and 5 placenta percreta. Only 1.1% of cases of placenta previa without prior cesarean section were increta/percreta, in contrast to 37% of placenta previa after prior cesarean sections. Mean intraoperation blood loss was 3630 +/- 2216 g (increta) and 12,140 +/- 8343 g (percreta). One patient with placenta previa percreta died of hemorrhage. Stepwise treatment (cesarean section without separation of the placenta, arterial embolization and hysterectomy) was applied for 4 cases, which had the least blood loss. CONCLUSIONS: Placenta previa increta/percreta is a life-threatening disease. Patients who undergo hysterectomy after uterine arterial embolization demonstrate reduced intraoperation blood loss, and this treatment should be incorporated to reduce maternal morbidity. PMID- 17845317 TI - Antepartum detection of cord presentation by transvaginal ultrasonography for term breech presentation: potential prediction and prevention of cord prolapse. AB - AIM: We evaluated the efficacy of antepartum screening for cord presentation by trans-vaginal ultrasonography (TVS) on predicting and preventing umbilical cord prolapse (UCP) in term breech delivery. METHODS: We investigated every woman with a breech-presenting fetus for cord presentation by weekly TVS after 36 weeks of gestation since 1995. If the cord was found in advance of fetal presenting parts, we recommended her to undergo elective cesarean section to avoid UCP. We studied the incidence of cord presentation by TVS and the clinical courses of the cases with it for 198 women who delivered breech after 36 weeks from 1995 to 2005 (group A). Further, the incidence of UCP was compared between group A and another 230 women who delivered breech at term from 1983 to 1994 (group B). RESULTS: Cord presentation was detected by TVS at least once in eight (4%) group A patients. Seven of them underwent elective cesarean section and, in six of these (86%), cord presentation was still found at the time of operation. The eighth patient became free of cord presentation at the later examinations and delivered vaginally without UCP. A hundred and twenty-one (61%) women in group A and 159 (69%) women in group B delivered vaginally. No UCP occurred in group A, while it occurred in 10 (4%) cases of group B (P < 0.01), and one baby died of it. CONCLUSIONS: Detection of cord presentation by TVS has a potential to predict and reduce UCP in breech delivery at term. PMID- 17845318 TI - Fetal manifestations and poor outcomes of congenital cytomegalovirus infections: possible candidates for intrauterine antiviral treatments. AB - AIM: This retrospective study was performed to reveal the natural history of cytomegalovirus (CMV) infected fetuses during the perinatal period and to find prenatal findings associated with poor outcomes. METHODS: 33 neonates with CMV infection, born after 30 weeks of gestation, were registered from a total of 12 414 infants between 1995 and 2003. Maternal and neonatal medical records were reviewed regarding fetal growth; abdominal signs including ascites and hepatosplenomegaly; cerebral signs including ventriculomegaly, microcephaly, and calcification; and fetal heart rate monitoring, for signs which may have been detected by the standard obstetric ultrasonography. Univariate and multivariate analyses were performed to test for any associations between these manifestations and poor outcomes such as death and neurological damages. RESULTS: Among the 33 infants, 6 died, 10 developed neurological damage including cerebral palsy (n = 8), epilepsy (n = 5), and hearing difficulties (n = 5), and the remaining 17 were normal. After adjusting for ganciclovir treatment and gender, death was 40-fold more likely associated with infants having abdominal signs (OR 40, 95%CI 4.6-930) than those without abdominal signs. Similarly, poor outcomes (death or neurological damage) were more likely associated with infants having either abdominal or cerebral signs (OR 39, 95%CI 3.8-1323). Fetal growth restriction and non-reassuring fetal heart rate patterns were not significantly associated with poor outcomes. CONCLUSION: The absence of abdominal signs guarantees the infant's survival. The presence of abdominal or cerebral signs is associated with poor outcomes, suggesting that these fetuses are possible candidates to receive in utero therapy of congenital CMV infection. PMID- 17845319 TI - Results of endovascular treatment in cases of abnormal placentation with post partum hemorrhage. AB - AIM: The purpose of this study was to evaluate the clinical success of selective arterial embolization in cases of post-partum hemorrhage due to abnormal placentation. METHODS: Six patients with persistent hemorrhage and abnormal placental implantation underwent uterine artery embolization over a period of three years. RESULTS: In four patients, the placenta was left in place after a gentle attempt at removal and post-partum hemorrhage was controlled during or shortly after the procedure. In all cases, embolization was possible even when there was previous arterial ligation (two cases). In one case, a hysterectomy was required at 21 d later due to uterus and bladder necrosis. Arterial embolization in cases of abnormal placental implantation remains an uncommon treatment and is less efficient in these cases than in normal placental implantation. CONCLUSION: Our results confirmed that even in cases of moderate bleeding, conservation treatment and embolization are possible, but that complications may be more common than in normal placentation. PMID- 17845320 TI - Celecoxib versus magnesium sulfate to arrest preterm labor: randomized trial. AB - AIM: The effectiveness of the management of preterm birth remains an important health care issue, especially when considering that more than two thirds of singleton neonatal death occurs in preterm labor. The purpose of this study was to compare oral celecoxib with intravenous magnesium sulfate as tocolytic. METHODS: This was a randomized study of patients who were between 24 and 34 weeks of gestation with preterm labor. One hundred and four pregnant women with preterm labor were randomly assigned to receive celecoxib 100 mg b.i.d. for 48 h or intravenous magnesium sulfate (MgSO4) for maximum of 48 h. Outcome variables included delay of delivery for 48 h and the incidence of side-effects. Data was analyzed using the Student t-test and the chi(2) test. RESULTS: There was no difference between the groups over the course of the study in demographic characteristics, cervical examination and amniotic fluid index. Labor was arrested for 48 h was in 42 (81%) and 45 (87%) of the patients in the celecoxib and magnesium sulfate groups, respectively (p-0.298). There were no severe maternal or neonatal complications in either group. CONCLUSION: Celecoxib is as effective as magnesium sulfate for primary tocolysis. PMID- 17845321 TI - Ultrasound-determined fetal subcutaneous tissue thickness for a birthweight prediction model. AB - AIM: The aim of this study was to explore a birthweight prediction model using ultrasound determined tissue thickness (SCTT) parameters. METHODS: We measured routine ultrasonographic biometric parameters and in addition, fetal SCTT in 201 healthy singleton pregnancies. Mid-arm fat and lean mass, mid-thigh fat and lean mass, subscapular fat mass and abdominal fat mass (AFM) were measured in order to calculate a birthweight prediction model. Ultrasound measurements were analyzed using an 'anovarepeated measures model'. The growth rate (beta-slope) of the selected parameters was computed and the correlation coefficient with the birthweight and the Kendall rank correlation tau, were calculated. RESULTS: From the ultrasound determined SCTT parameters, only abdominal circumference (AC), AFM, and MTLM showed a statistically significant trend. The beta-slope of mid thigh lean mass was excluded since it exhibited significant correlation with the beta-slope of AFM. The final regression model could be calculated as: birthweight (gr.) = intercept +alpha(1)(AFM beta-slope) + alpha(2)(AC beta-slope), where alpha(1), alpha(2) represent regression coefficients. CONCLUSIONS: We provide a graphical birthweight prediction model for clinical practice using conventional and specific ultrasound measurements of fetal subcutaneous tissue thickness. This model is based upon an overall analysis of the ultrasound estimated body components. PMID- 17845322 TI - Length of the third stage of labor at term pregnancies is shorter if placenta is located at fundus: prospective study. AB - AIM: To investigate how the location of the placenta at term pregnancies affects the duration of the third stage of labor and to discuss the possible mechanisms affecting the duration of the third stage. We believe that this is the first prospective study comparing the duration of the third stage of labor according to placental location. METHODS: The placental implantation was determined as anterior (n = 78), posterior (n = 59), or fundal (n = 64) by ultrasound, in 201 women with singleton pregnancies. After delivery of the newborn, oxytocin infusion was routinely given. Duration of the third stage of labor was compared by anova. P < 0.05 was determined as significant. RESULTS: The duration of the third stage of labor was 10.36 +/- 5.94 min, 10.44 +/- 5.35 min, and 8.12 +/- 4.25 min with placentas located anteriorly, posteriorly, and fundal, respectively. The length of the third stage was significantly shorter in the fundal placenta group. CONCLUSION: In this study, the length of the third stage of labor was approximately 2 min shorter with placentas located at the fundus compared to the other two groups. The mechanism responsible for shorter duration may be the bipolar separation of fundal placentas in contrast to usual unipolar down-up separation of anterior or posterior placentas. Another contributing factor may be the use of oxytocin infusion for the management of the third stage, however this should be investigated by further studies by using real time ultrasonography. PMID- 17845323 TI - Plasma levels of alpha-defensins 1-3 are an indicator of neutrophil activation in pregnant and post-partum women. AB - AIM: In severe preeclampsia and septic shock, excessively activated neutrophils are thought to injure tissue irreversibly. On the other hand, mild neutrophil activation is known to occur during normal pregnancy. The objective of this study was to determine whether elevated plasma levels of alpha-defensins 1-3 could be used as an indicator of neutrophil activation in pregnant and post-partum women. METHODS: Defensin concentrations in 21 non-pregnant women and men, 184 normal pregnant women, and 55 post-partum women were quantified using an enzyme-linked immunosorbent assay (ELISA). The expression of the surface markers, CD11b and Toll-like receptor-4 (TLR-4), on the neutrophils were analyzed by flow cytometry in a cohort of subjects different from that used for the analysis of alpha defensin levels. RESULTS: The concentrations of alpha-defensins were significantly higher in women that were in labor than in any of the other subjects. These levels diminished after delivery, but remained significantly elevated at one month post-partum. The expression of both CD11b and TLR-4 was significantly higher in women in labor compared to non-pregnant donors (controls). CD11b expression remained high on the third post-partum day, while TLR-4 expression fell to non-pregnant levels. CONCLUSION: Our results suggest that there is a positive association between defensin levels and neutrophil activation in pregnant and post-partum women. PMID- 17845324 TI - Evaluation of pregnant women with scarred uterus in a low resource setting. AB - AIM: Management of post cesarean pregnancy continues to be a dilemma. The present study was undertaken to evaluate the outcome of such pregnancies in a resource constrained setting so that an appropriate management protocol can be decided. METHODS: An observational study was conducted in the Department Of Obstetrics And Gynecology, King George's Medical University, Lucknow, India. The outcome of all of the women admitted with pregnancy with a previous cesarean section was noted. RESULTS: A total number of 447 women with a post cesarean pregnancy underwent delivery. These comprised 13.7% of total deliveries over the same period. 124 women (27.7%) had successful vaginal delivery while 323 (72.3%) had a repeat cesarean section. Maternal morbidity and perinatal mortality were both significantly higher in the vaginal delivery group (P = 0.00211 and P = 0.0426, respectively). CONCLUSIONS: Vaginal birth after cesarean (VBAC) is associated with higher maternal morbidity and perinatal mortality. Therefore the decision for VBAC must be taken only after proper consideration and counseling of the couple. PMID- 17845325 TI - Impact of maternal body mass index on obstetric outcome. AB - AIM: The purpose of the present study was to correlate effect of maternal body mass index (BMI) on obstetric outcome. The studies conducted so far are from Western developed countries and there is a paucity of data from developing countries. METHODS: A prospective evaluation was carried out of 380 women in one unit of a tertiary care teaching hospital in North India from May 2005 to June 2006 on the effect of maternal BMI on pregnancy outcome. BMI was calculated as weight (kg) divided by height (m(2)). BMI was used to characterize women as lean (BMI < 19.8 kg/m(2)), normal (BMI 19.9-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)) or obese (> or =30 kg/m(2)). RESULTS: Forty-six women (12.1%) out of 380 were underweight, 99 (26.1%) were overweight, 30 (7.9%) were obese and the remaining 205 (53.9%) had normal BMI. Anemia (P = 0.02) and low birthweight (P = 0.008) was significantly present among lean women. Obese women had a significant risk for gestational diabetes (P = 0.0004), pre-eclampsia (P = 0.004), cesarean delivery (P = 0.01) and macrosomia (P = 0.02). CONCLUSION: Both lean and obese women carry a risk for adverse pregnancy outcome, therefore pregnant women should maintain a normal BMI to achieve a healthy pregnancy outcome. PMID- 17845326 TI - Cervical intraepithelial neoplasia II-III with endocervical cone margin involvement after cervical loop conization: is there any predictor for residual disease? AB - AIM: To determine the clinicopathological predictors for residual disease in women who have had cervical intraepithelial neoplasia (CIN) II-III with endocervical cone margin involvement after loop electrosurgical excision procedure (LEEP). METHODS: All of the women who had CIN II-III on LEEP specimens with endocervical margin involvement, and underwent subsequent surgical treatment including repeat LEEP or hysterectomy at Chiang Mai University Hospital between May 2003 and June 2006 were reviewed. RESULTS: During the study period, 85 women who matched the study inclusion were identified. The mean age was 48.6 years. Fifty-two women (61.2%) were postmenopausal. The most common Pap smear before LEEP was high-grade squamous intraepithelial lesion (HSIL) (65.9%), followed by squamous cell carcinoma (21.2%). Twenty-five women (29.4%) had concurrent ectocervical and endocervical cone margin involvement. Residual disease was noted in 44 women (51.8%, 95%CI = 40.7-62.7) of whom six had unrecognized invasive squamous cell carcinoma, while the remaining 38 had CIN II-III. Only extensive endocervical cone margin involvement (3-4 quadrants) was noted as the significantly independent predictor for residual disease (aOR = 14.2, 95% CI = 3.6-55.8; P < 0.001). CONCLUSION: Extensive endocervical cone margin involvement after LEEP for CIN II-III is a strong predictor for residual disease. Therefore, the number of involved quadrants should be evaluated to plan further management. PMID- 17845327 TI - Laparoscopy should be strongly considered for women with unexplained infertility. AB - AIM: Women with unexplained infertility frequently become pregnant after diagnostic laparoscopy. In this study the effect of laparoscopic surgery on such women was evaluated by the pregnancy rate after laparoscopic surgery. METHODS: A total of 47 unexplained infertile women underwent laparoscopic evaluation during the period August 2002 to January 2005 in our center. The percentage of positive laparoscopic findings and the pregnancy rate after laparoscopy were calculated. The patients were divided into 5 subgroups according to maternal age, pregnancy rates were calculated for each group, and compared with the outcome of assisted reproductive technology (ART) treatment for the same age groups. RESULTS: In 87.2% of the women, laparoscopy revealed abnormal findings; endometriosis lesions, peritubal adhesions and tubal obstructions were found in 21, 17 and 3 cases, respectively. After laparoscopy 23 achieved pregnancy (pregnancy rate: 48.9%). The pregnancy rates of the groups at the age of 25 years old or less, 26 30, 31-35, 36-40 and over 41 years old were 100%, 75.0%, 45.5%, 27.2% and 0%, respectively. In the case of the 26-30 years old group, the pregnancy rate after laparoscopy was significantly higher than that in the ART treatment group (33.3%, P < 0.05). CONCLUSIONS: Laparoscopy should be strongly considered for examining women with unexplained infertility. PMID- 17845328 TI - Impact of laparoscopic cystectomy on fecundity of infertility patients with ovarian endometrioma. AB - AIM: To clarify the effect of laparoscopic cystectomy for ovarian endometrioma in infertility patients, the pregnancy outcome was evaluated. METHODS: This was a retrospective study. From August 2002 to February 2006, 33 infertility patients with ovarian endometrioma underwent laparoscopic cystectomy at our center. According to the laparoscopic findings 33 were divided into two groups; 10 were evaluated as the patients who need assisted reproductive technologies (ART) treatment (IVF subgroup) and 23 were evaluated as the patients who do not need ART treatment but conventional infertility treatment (non-IVF subgroup). During the same period, 70 patients who were age-matched and received ART treatment without laparoscopy were defined as control (control group). Following up to 12 months after laparoscopy, the cumulative pregnancy rate in the non-IVF subgroup was calculated. RESULTS: The patients age, duration of infertility and size of endometrioma were equal in the IVF and the non-IVF subgroups. The revised American Society of Reproductive Medicine (r-ASRM) score in the IVF subgroup was significantly higher than that in the non-IVF group (P < 0.05). The pregnancy rates after laparoscopic cystectomy in IVF and non-IVF subgroups were 50.0% and 60.9%, respectively. These rates in the IVF and the non-IVF groups were slightly higher than that in control group (41.4%), but these differences were not significant. The cumulative pregnancy rate in the non-IVF group reached 52.2%, 12 months after laparoscopic surgery. CONCLUSIONS: Laparoscopic surgery should be performed prior to ART treatment not only for making a decision about the treatment course but also for establishing a good pelvic condition to induce a pregnancy during ART treatment in infertility treatment with ovarian endometrioma. PMID- 17845329 TI - Clinical, endocrine and ultrasonographic features of polycystic ovary syndrome in Thai women. AB - AIM: To study the prevalence, reproductive hormone profiles and ovarian sonographic appearance of Thai women with polycystic ovary syndrome (PCOS). METHODS: One thousand and ninety-five women were screened for oligomenorrhea/amenorrhea, and the clinical symptoms of hyperandrogenism. Ovarian morphology and volume were assessed by ultrasonography in diagnosed cases. Blood was taken for the measurement of the follicle stimulating hormone, luteinizing hormone, prolactin, testosterone, androstenedione, dehydroepiandrosterone and 17 hydroxyprogesterone. RESULTS: The prevalence of PCOS was 5.7%. The mean age of women with PCOS was less than that of non-PCOS cases (27.4 +/- 6.5 and 31.1 +/- 6.4 years, respectively; P < 0.0001). Abnormal uterine bleeding and infertility were the leading presenting symptoms. The mean ovarian volume in women with PCO appearance was 9.22 +/- 4.36 mL compared to 6.53 +/- 3.31 mL in those without this appearance (P = 0.04). Hyperandrogenemia was confirmed in 23 of the 62 cases (37.1%). CONCLUSIONS: The prevalence and clinical presentations of Thai women with PCOS were similar to those in other reports. However, hirsutism, elevated testosterone level and acanthosis nigricans were uncommon in our population. Serum androstenedione was a more sensitive indicator of hyperandrogenemia than total testosterone. Further research is needed to clarify whether there is an ethnic difference in endocrine profiles and risks of metabolic syndrome. PMID- 17845330 TI - Morphometric study of GnRH analog/HMG/HCG effects on ultrastructure of human endometrial epithelium in early and mid-luteal phase. AB - AIM: The aim of the present study was to investigate the effects of long protocol ovulation induction on the ultrastructure of the human endometrial epithelium on days luteinizing hormone (LH) + 4 and LH+ 6 of the menstrual cycle. METHODS: Endometrial biopsies were obtained on days LH+ 4 (n = 9) and LH+ 6 (n = 10) from infertile women who were under standard long protocol with luteal phase supplementation with IM (intramuscular) progesterone, but where the embryo had not been formed or transferred, due to the male factor problem. Biopsies were also taken on days LH+ 4 (n = 5) and LH+ 6 (n = 5) from fertile women who had not received ovulation induction drugs as control groups. After preparation and taking light and electron micrographs from samples, qualitative and quantative evaluations (morphological and morphometric) were accomplished and the data was compared using the unpaired student t-test. RESULTS: Qualitative results showed the presence of the nuclear channel system, vacuoles of glycogen and giant mitochondria in all of the samples. Qualitative analysis showed that the volume fraction (Vv) of the euchromatin to the nucleus, the rough endoplasmic reticulum and the mitochondria to the cell, were not statistically different (P > 0.05) in samples taken on LH+ 4 in both control and test groups. The Vv of these features, however, to the cell in the test group was significantly (P < 0.05) higher than those in the control taken on LH+ 6. CONCLUSIONS: These results suggest that long protocol ovulation induction with luteal phase support with progesterone alter the normal development of the human endometrium in the mid luteal phase and could decrease the implantation success rate. PMID- 17845331 TI - Association of Chlamydia trachomatis serology with tubal infertility in Nigerian women. AB - AIM: To determine the association between tubal infertility and Chlamydia trachomatis in Nigerian women. METHODS: This case-control study is from the Departments of Obstetrics and Gynecology of two tertiary hospitals in Nigeria. One hundred and sixty-two infertile patients with tubal occlusion had 162 pregnant women matched for age as controls. Information on sociodemographic variables, sexual and reproductive risk factors, and history of previous pelvic infections were elicited using a study protocol. The prevalence of Chlamydia Trachomatis antibody was determined for cases and controls. RESULTS: The prevalence of serum Chlamydia antibody was significantly higher in cases (65.8%) compared with controls (17.3%; P < 001). The effects of Chlamydia antibodies on infertility were strengthened in the multivariate model controlling for Chlamydia antibodies and gynecologic symptoms, compared to the univariate model. However, the association was attenuated and non-significant when the effects of gynecologic symptoms, sociodemographic characteristics, contraceptive and sexual history were controlled in the conditional logistic regression model. The strongest independent predictors of infertility in the model were vaginal discharge, education less than tertiary and more than three lifetime sexual partners (proxies of sexually transmitted infections). CONCLUSIONS: There was no strong independent association between Chlamydia antibodies and the risk of being infertile in Nigerian women. By contrast, the proxies of sexually transmitted infections were significant predictors of infertility in the women. Efforts to address these factors, which are proxies of sexually transmissible infections, Chlamydia infection, and health-seeking behavior for these infections, will likely contribute to reducing the burden of infertility in Nigerian women. PMID- 17845332 TI - Aromatase inhibitor-induced bone mineral loss and its prevention by bisphosphonate administration in postmenopausal breast cancer patients. AB - AIM: To investigate aromatase inhibitor-induced bone mineral loss and its prevention by bisphosphonate administration in postmenopausal breast cancer patients. METHODS: Subjects were 17 postmenopausal breast cancer patients (mean age, 63.3 +/- 9.9 years) receiving non-steroidal aromatase inhibitor (AI; anastrozole, 1 mg daily) only and 10 such patients (mean age, 65.0 +/- 5.1 years) receiving AI + bisphosphonate (risedronate sodium, 2.5 mg daily) for 6 months. All of the subjects had undergone surgical resection and had positive estrogen receptor tumor status. Age, age at menopause, years since menopause, height, weight, and body mass index (Wt/Ht(2)) were recorded. Lumbar spine (L2-4) bone mineral density (BMD), T-, and Z-scores were assessed on dual-energy X-ray absorptiometry before and after therapy. RESULTS: In the AI-only group BMD, T-, and Z-scores significantly decreased from the baseline during the 6-month therapy period (P < 0.05). Mean decreases in L2-4 BMD and Z-score were 2.5% and 3.0%, respectively. In the AI + bisphosphonate group, however, BMD, T-, and Z-scores significantly increased from the baseline values (P < 0.01). Mean increases in L2 4 BMD and Z-score were 4.5% and 3.3%, respectively. CONCLUSION: AI carries a potential risk of bone mineral loss despite the short therapy duration. Bisphosphonate has a preventive effect on this loss. PMID- 17845333 TI - Efficacy and outcome of anterior vaginal wall repair using polypropylene mesh (Gynemesh). AB - AIM: The aim of the present study was to assess the safety and efficacy of anterior vaginal wall repair using polypropylene mesh for the correction of anterior vaginal wall prolapse. METHODS: From May 2001 to March 2005, 38 patients with cystoceles or uterine prolapse underwent transvaginal repair with implantation of polypropylene mesh. In all 38 patients anterior vaginal wall repair was done concurrently with other procedures: vaginal hysterectomy, n = 18 (47.4%) and tension-free vaginal tapes n = 22 (57.9%). RESULTS: Preoperatively 26 patients (68.4%) had stage III/IV prolapse on pelvic organ prolapse quantification examination. After mean follow up of 23.4 months, the objective cure rate at 12 and 18 months was 94.5% and 94.3%, respectively. As for complications associated with placement of the polypropylene mesh, no tissue erosion or infection was found. CONCLUSIONS: Transvaginal implantation of polypropylene mesh is an effective and safe technique for the correction of anterior vaginal wall prolapse. PMID- 17845334 TI - Major complications and outcome of diagnostic and operative transvaginal hydrolaparoscopy. AB - AIM: Transvaginal hydrolaparoscopy (THL) has recently been developed as a less invasive alternative to conventional laparoscopy. There are some reports that described the usefulness and prognostic value of diagnostic THL in infertile women. Moreover, operative THL such as ovarian drilling for unovulatory women with polycystic ovarian syndrome (PCOS) to induce ovulation has also been found to be as effective as that by conventional laparoscopy. The risk of bowel injury and sepsis by transvaginal access with culdoscopy was higher than that with laparoscopy in the previous reports. The purpose of the present study was to examine the risk of diagnostic and operative THL according to two case studies with a literature review. METHODS: The authors carried out diagnostic or operative THL in 177 infertile women, aged 22-43 years. Major complications during THL and a review of the literature were analyzed. RESULTS: Two cases of bowel injury were diagnosed during diagnostic THL. No complication occurred during operative THL. In total, the incidence of bowel injury was 1.1%. The injuries were diagnosed during THL and treated expectantly under strict conditions in both cases. Ten studies in the literature reported a total of 4232 procedures, including 26 bowel injuries (0.61%) and one perforation of a retroflexed uterus (0.02%). CONCLUSIONS: The usefulness of THL for diagnostic and operative purposes is in no doubt. However, informed consent should be obtained and vigilance before and during THL should be maintained, although it can be done on an outpatient clinic basis. PMID- 17845335 TI - Nitric oxide metabolite levels in preterm labor. AB - AIM: To investigate the role of nitric oxide metabolites as markers of infection in subjects with preterm labor or preterm premature rupture of membranes (PTPROM). PTPROM means that there was spontaneous rupture of fetal membrane before the onset of labor and gestational age was <37 weeks. This occurs because of imbalance between matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase. The cause of this imbalance that leads to degradation of collagen causing PTPROM is infection. The bactericidal, fungicidal, viricidal and tumoricidal activities of macrophages are determined in part by elaboration of nitric oxide, hence nitric oxide levels have been found to be increased in infections. METHODS: During an 18-month period 50 women with preterm labor or PTPROM and 50 controls were enrolled prospectively. Blood and urine samples were obtained for analysis of nitric oxide metabolites. Patients with known causes of preterm labor were excluded. RESULT: The nitric oxide metabolites, which included both nitrite levels and citrulline levels were significantly higher both in blood as well as urine in patients with preterm labor and PTPROM compared to controls. Serum nitrite levels in subjects with preterm labor were 376.5 +/- 345 nmol/L while in subjects with PTPROM they were 295.7 +/- 161.1 nmol/L and in controls the levels were 62.7 +/- 33.9 nmol/L. Serum citrulline levels in subjects with preterm labor were 5293.8 +/- 2916.7 nmol/L; in PTPROM they were 6536.6 +/- 609.91 nmol/L and in controls they were 949.8 +/- 67.1 nmol/L. On comparing patients with preterm labor, those in whom preterm labor could not be inhibited had statistically significant higher levels of nitrite in both serum and urine (482.9 +/- 387.7 nmol/L and 754.5 +/- 336.5 nmol/L, respectively) compared to patients in whom labor could be inhibited (172.2 +/- 61.9 nmol/L and 401.8 +/- 236.9 nmol/L, respectively). The citrulline levels were also higher among the group who delivered preterm for both serum and urine (5355.4 +/- 3229.7 nmol/L and 11 482.8 +/- 2541.4 nmol/L, respectively) compared to patients in whom labor could be inhibited (5260.2 +/- 2897.08 nmol/L and 10 651.4 +/- 1502.7 nmol/L, respectively) but this did not reach statistical significance. CONCLUSION: Higher nitric oxide metabolites in women with preterm labor are marker of subclinical infection. PMID- 17845336 TI - Intrauterine therapy with cytomegalovirus hyperimmunoglobulin for a fetus congenitally infected with cytomegalovirus. AB - Reported herein is a case of hydrops fetalis in which the cord blood expressed cytomegalovirus (CMV) antigen. Fetal ascites was removed from an infected fetus with hydrops in utero and 2.5 g CMV hyperimmunoglobulin was administered into the fetal abdominal cavity at 28 weeks gestation. After immunoglobulin administration, fetal ascites vanished, preload index of the inferior vena cava decreased and platelet count of the infant increased. However, despite intrauterine therapy and intensive neonatal care, the infant died soon after birth. The expression of CMV antigen in the nucleus of polymorphonuclear leukocytes in fetal cord blood indicated that the fetal hydrops was caused by CMV infection. When symptomatic CMV infection of a fetus is suspected from serological and ultrasound findings, further examinations should be performed for the diagnosis. Intrauterine immunoglobulin therapy could be one of the therapeutic options for the affected fetus. PMID- 17845337 TI - Prophylactic trans-uterine embolization to reduce intraoperative blood loss for placenta percreta invading the urinary bladder. AB - Reported herein is the case of a 35-year-old multipara woman diagnosed (on sonography) with total placenta previa that had ruptured through the myometrium of the uterus, invading the wall of the urinary bladder. In the 32nd week of gestation the patient underwent an emergency cesarean section due to profuse vaginal bleeding. Due to possible intraoperative massive bleeding during removal of the placenta it was decided to preserve the uterus and placenta temporarily. The patient underwent superselective trans-uterine embolization through the bilateral anterior branches of the hypogastric arteries, using gelfoam cubes and coils. Two days later cesarean hysterectomy was performed, and the placenta was successfully removed from the invaded urinary bladder. The whole procedure went smoothly and the estimated blood loss was only 1300 mL. PMID- 17845338 TI - Sudden fetal hemorrhage from umbilical cord ulcer associated with congenital intestinal atresia. AB - There have been several reports of umbilical cord ulcer (UCU) associated with congenital intestinal atresia, many cases of which have been reported with fetal or neonatal death. Herein is described the case of a fetus with jejunal atresia complicated by acute massive intrauterine hemorrhage due to the perforation of UCU resulting in an intact survival. Although the onset of critical condition in the present case was noted due to continuous fetal heart rate (FHR) monitoring, it is necessary to establish the management of congenital intestinal atresia to prevent this life-threatening fetal hemorrhage. PMID- 17845339 TI - Perforated colon volvulus coiling around the uterus in a pregnant woman with a history of severe constipation. AB - A case of intestinal volvulus in both the sigmoid colon and cecum in a pregnant woman suffering from severe constipation is reported herein. The fetus was dead and the mother developed acute shock. The twisted sigmoid colon coiled twice around the uterus and was perforated. The mother died 10 h after the onset of severe abdominal pain. Volvulus should be considered when examining severe abdominal pain in a pregnant woman with a history of severe constipation. Early suspicion together with prompt intervention will minimize maternal and fetal morbidity and mortality of this rare complication of pregnancy. PMID- 17845340 TI - Late onset of pulmonary embolism caused by lymphocyst following pelvic lymphadenectomy. AB - Herein is reported a case of late-onset pulmonary embolism following pelvic surgery, despite prophylactic measures in the perioperative period. Twenty-six days after hysterectomy and pelvic lymphadenectomy for endometrial carcinoma, an 83-year-old woman developed a pulmonary embolism. This was caused by pelvic lymphocyst, which, in turn, led to chronic compression of the right external iliac vein. This case strongly suggests that prolonged postoperative thromboembolic prophylaxis should be considered in elderly patients undergoing lymphocyst following pelvic surgery. PMID- 17845341 TI - Simple sling resection and a second, intermediate polypropylene mesh for treatment of vaginal tape protrusion concurrent with recurrent urinary stress incontinence after TVT procedure. AB - The tension-free vaginal tape (TVT) procedure is a simple, effective and minimally invasive method for the surgical treatment of urodynamic stress incontinence (USI). Yet, complications such as mesh protrusion and recurrent urinary leakages after TVT have been reported. A case of recurrent USI complicated with vaginal mesh protrusion following a TVT procedure was referred. Video-urodynamics and introital ultrasonography confirmed that the recurrence of USI was secondary to mal-position of the protruded TVT. A simple salvaging procedure was carried out. The mal-positioned distal protruded TVT was resected and a second intermediate piece of polypropylene (Prolene) mesh was replaced at mid-urethra. The operation time was short and blood loss was minimal. The patient was objectively continent at 6 months follow-up with no defect of healing. Considering the cost-effectiveness and invasiveness of the surgeries, the method of inserting an intermediate mesh is clinically useful. PMID- 17845342 TI - Re: reducing postpartum hemorrhage in Vietnam: assessing the effectiveness of active management of third-stage labor. PMID- 17845343 TI - Role of aromatase inhibitor in patients with poor response to clomiphene citrate needs further evaluation. PMID- 17845365 TI - Assisted reproductive technology in Israel. PMID- 17845366 TI - Isolation and identification of putative stem/progenitor cells from human cycling endometrium. PMID- 17845367 TI - Indigenous women's health: an Australasian perspective. PMID- 17845369 TI - New tides: updates in the management of preterm labor and delivery and pre eclampsia. PMID- 17845370 TI - New tide for women with polycystic ovary syndrome. PMID- 17845372 TI - Asia and Oceania Federation of Obstetrics and Gynaecology (AOFOG) 1957-2007. PMID- 17845373 TI - Coeliac disease and dietitians--are we getting it right? PMID- 17845374 TI - A survey of provision of dietetic services for coeliac disease in the UK. AB - BACKGROUND: Management guidelines for care of coeliac patients published by the British Society of Gastroenterology (BSG), 2002 recommend that patients should see a dietitian at diagnosis and at least at annual review. In the absence of information on dietetic provision in coeliac disease management in the UK and with surveys in other countries suggesting that patients with coeliac disease gain most information from coeliac support groups (Green et al., 2001), Coeliac UK set out to investigate dietetic services for coeliac patients in the UK. METHODS: Questionnaires were sent to dietetic departments in the UK via the Regional Managers Group of the British Dietetic Association (BDA) by email. The questionnaires were in two parts, the first was completed by the dietetic manager and the second by the dietitian with the main responsibility for the management of coeliac patients within the department. RESULTS: Over one-quarter of departments reported allocating a maximum of 1 h of dietitians' time per month per 100,000 population to seeing coeliac patients. More hours were allocated to coeliac patients in departments where dietitians had attended coeliac disease training, where dietitians were professional members of Coeliac UK or where coeliac patient care was undertaken by a multi-disciplinary team. CONCLUSION: There is wide variation in dietetic provision for diagnosed coeliac patients in the UK. The Coeliac UK survey suggests that the current level of dietetic provision is in the region of one-third of what is required according to the BSG management guidelines (British Society of Gastroenterology (BSG), 2002) to provide diagnosed coeliacs with only basic support and annual review. PMID- 17845375 TI - Sharing life with a gluten-intolerant person--the perspective of close relatives. AB - BACKGROUND: Several studies indicate the importance of social support in the case of chronic disease. AIM: The aim was to explore dilemmas experienced by close relatives living with a person suffering from coeliac disease, and to describe the strategies they used to deal with these dilemmas. METHODS: Twenty-three informants were interviewed. A systematic inductive qualitative method, the critical incident technique was used. RESULTS: Disease-related worries included having bad conscience about not being affected by the disease, experiencing anxiety and witnessing the vulnerability of the affected relative in social situations. Dilemmas related to manage daily life were connected with increased domestic work, restricted freedom of action and the diseased person's preferential right of interpretation of health risks associated with the coeliac disease and deviations from the diet restrictions. Dilemmas related to disturbances in social life, concerned lack of information, knowledge and understanding. Different strategies were described to manage daily life. CONCLUSIONS: Close relatives experienced a variety of dilemmas that affected the situation of the whole family. The role of relatives in handling the coeliac disease with the diseased person in the everyday life might be underestimated, and to provide relatives with better knowledge regarding the disease might improve the situation also for patients. PMID- 17845376 TI - Economic burden of a gluten-free diet. AB - BACKGROUND: Coeliac disease is a common, autoimmune disorder, for which the only treatment is lifelong adherence to a gluten-free diet. This study evaluates the economic burden of adhering to a gluten-free diet. METHODS: A market basket of products identified by name brand, weight or package size for both regular wheat based products and gluten-free counterparts was developed. The differences in price between purchase venues, both type of store (general grocery store, an upscale grocery store and a health food store and four internet-based grocery sites) and region was also analysed. RESULTS: Availability of gluten-free products varied between the different venues, regular grocery stores carried 36%, while upscale markets carried 41%, and health food stores 94%, compared with 100% availability on the internet. Overall, every gluten-free product was more expensive than their wheat-based counterpart (P 50%) and the ultrasonographic investigation of both kidneys was normal. She could be discharged after four and a half months hospitalization and lived well as an outpatient for a further two months. She died shortly after readmission from multiple organ failure without the relapse of TTP. The patient's clinical course would suggest that TTP post mini-alloPBSCT could be treated with PE in some cases, despite the development of dialysis-requiring severe ARF being a poor prognostic factor. PMID- 17845403 TI - Comment on "Midodrine hydrochloride and L-threo-3,4-dihydroxy-phenylserine preserve cerebral blood flow in hemodialysis patients with orthostatic hypotension" by Fujisaki et al. PMID- 17845404 TI - Under the spotlight: skin therapy for asthma. PMID- 17845405 TI - Asthma: advancing gene-environment studies. PMID- 17845406 TI - Suppression of the asthmatic phenotype by ultraviolet B-induced, antigen-specific regulatory cells. AB - BACKGROUND: Over recent decades, there has been a significant global increase in the prevalence of asthma, an inflammatory disease of the respiratory system. While ultraviolet radiation (UV) has been used successfully in the treatment of inflammatory conditions such as psoriasis, studies of UV-induced regulation of allergic respiratory responses have been rare, and have not analysed in vivo measurements of airway hyperresponsiveness (AHR) or the antigen specificity of the UV-induced effects. OBJECTIVE: To investigate the regulatory properties of erythemal ultraviolet B (UVB) irradiation of the skin and the induction of allergen-induced airway immunity in a murine asthma model, and to examine the mechanisms involved. METHODS: BALB/c mice were exposed to a single erythemal dose of UV 3 days before intraperitonial sensitization (day 0) and boost (day 14) with the antigen, ovalbumin (OVA). Airway-associated, asthma-like responses to aerosolized OVA at day 21 were analysed including (a) AHR measured in vivo, (b) OVA-specific proliferative responses and cytokine production by cells from the lung-draining lymph nodes (LDLN), and (c) inflammatory cells and cytokines in the bronchoalveolar lavage fluid. To determine UVB-induced mechanisms of regulation, LDLN cells from UVB irradiated, OVA-sensitized mice were adoptively transferred into naive BALB/c mice that were subsequently sensitized and challenged with OVA, or a non-specific antigen. RESULTS: UVB irradiation of skin significantly suppressed AHR to methacholine and OVA-specific responses in the LDLN and in the lung compartment. Reduced OVA-specific responses by LDLN cells from both UVB irradiated mice and mice that received 5 x 10(6) LDLN cells from UVB irradiated, but not from non-irradiated, OVA-sensitized mice suggested that UVB-induced regulatory cells are responsible for many of the asthma-reducing effects of dorsal UVB exposure. CONCLUSION: UVB irradiation of skin suppresses AHR and cellular responses of the airways to respiratory allergens. Further, this study implicates UVB or its downstream mediators as a potential approach to reducing the severity of asthma. PMID- 17845407 TI - Clinical improvement and immunological changes in atopic dermatitis patients undergoing subcutaneous immunotherapy with a house dust mite allergoid: a pilot study. AB - BACKGROUND: House dust mites (HDMs) represent significant indoor allergen sources for patients with atopic dermatitis (AD). Subcutaneous allergen-specific immunotherapy (SCIT) has been shown to be successful in patients with allergic rhinitis and mild asthma and might represent an attractive therapeutic option for the long-term treatment of HDM sensitizations in AD patients. However, only a few studies have been conducted on the effectiveness of HDM SCIT in AD, resulting in controversial clinical results. Data on immunological changes induced by SCIT in AD patients are rare. OBJECTIVES: We performed an open pilot study to assess clinical changes and objective laboratory parameters and evaluate the benefit of HDM SCIT in 25 AD patients with IgE-mediated sensitization against HDM. METHODS: The severity of AD was evaluated by the severity scoring of atopic dermatitis system (SCORAD). Specific IgE and IgG4 against HDM and serum levels of TARC/CCL17, MDC/CCL22, IL-16, IL-4, IFN-gamma, IL-10 and TGF-beta1 were measured during SCIT. RESULTS: Subjective and objective SCORAD improved significantly within only 4 weeks of treatment. The level of the tolerogenic cytokine IL-10 increased, whereas CCL17 and IL-16 decreased in the sera of the patients during SCIT. Allergen specific IgE decreased, while IgG4 increased during SCIT. CONCLUSION: In this open-label pilot study, SCIT with an HDM extract in patients with AD led to a significant improvement of AD mirrored by a reduction of SCORAD as well as serological and immunological changes, which might serve as valuable parameters to estimate the therapeutic effect of SCIT. PMID- 17845408 TI - In vivo and in vitro immunomodulation of Der p 1 allergen-specific response by Lactobacillus plantarum bacteria. AB - BACKGROUND: Lactic acid bacteria (LAB) were reported to reduce some allergic manifestations in mice and humans but their impact on the aeroallergen-dependent immune mechanisms is still debated. OBJECTIVE: The potential capacities of Lactobacillus plantarum NCIMB8826 to reduce the allergic response induced by Der p 1, the major house dust mite allergen of Dermatophagoides pteronyssinus, were evaluated in vivo and in vitro. Methods First, the effect of the intranasal co administration of LAB and purified Der p 1 allergen before a sensitization protocol was evaluated. The allergen-specific antibody and cellular responses as well as airway inflammation were measured. Second, the impact of LAB on the cytokine profile of spleens cells from Der p 1-sensitized mice was assessed. Third, upon stimulation with LAB, the levels of cytokine produced by dendritic cells derived from the bone marrow (BMDCs) of wild-type, Toll-like receptor 2 (TLR2)-, TLR4- and MyD88-KO mice were compared. Results The co-application of L. plantarum and Der p 1 induced a T-helper type 1 (Th1)-biased allergen-specific IgG response, the absence of specific IgE response and favoured the production of INF-gamma upon allergen re-stimulation. Moreover, the previous LAB administration reduced the development of bronchoalveolar lavage eosinophilia usually induced by aerosol exposure. Additionally, the studied LAB strain was shown to modify in vitro the cytokine level produced by Der p 1-sensitized spleen cells mainly towards a Th1 profile. Finally, L. plantarum stimulated high IL-12 and moderate IL-10 production in mouse BMDCs notably through the TLR2-, MyD88-dependent and TLR4-independent pathway. CONCLUSION: In vivo co-administration of probiotic LAB with Der p 1 might prevent the development of the mite allergic response. The probiotic L. plantarum was shown to display in vitro therapeutic potentials for the treatment of allergy and to trigger the immune system by a TLR2- and MyD88 dependent signalling pathway. PMID- 17845409 TI - Early predictors for developing allergic disease and asthma: examining separate steps in the 'allergic march'. AB - BACKGROUND: Sensitization and symptoms of allergic disease are strongly correlated, but little is known about the early clinical precursors of the development of allergen sensitization in childhood. The aim of this study was to identify these predictors, and to examine separately the effect of early sensitization on subsequent wheeze, asthma, rhinitis and eczema. METHODS: In the Childhood Asthma Prevention Study, children with a family history of asthma were assessed for allergen sensitization, total serum IgE, wheeze, asthma, eczema and rhinitis at ages 18 months and 5 years. To examine predictors, at 18 months, for subsequent sensitization, children who were non-sensitized at 18 months and had data on sensitization at 5 years were investigated, n=375. To examine the predictors, at age 18 months, of subsequent onset of symptoms, children who did not have wheeze, asthma, eczema or rhinitis at 18 months were followed-up at 5 years, n=177. RESULTS: Among children who were non-sensitized at age 18 months, the presence of eczema [adjusted relative risk (aRR), 1.67, 95% confidence interval (CI) 1.20-2.33], but not wheeze, asthma or rhinitis, was an independent predictor of the onset of sensitization by age 5 years. Among children who were asymptomatic at age 18 months, sensitization to any allergen at 18 months was an independent predictor for the presence of wheeze (aRR 2.41, 95% CI 1.28-4.55), asthma (aRR 4.66, 95% CI 1.88-11.54) and rhinitis (aRR 1.77, 95% CI 1.08-2.90), but not for the development of eczema (aRR 0.78, 95% CI 0.23-2.64) at 5 years. CONCLUSION: In non-sensitized children, eczema, but not wheeze, asthma or rhinitis is a predictor for subsequent development of sensitization. This suggests that early childhood eczema, rather than wheeze and rhinitis, may promote subsequent allergen sensitization and raises the possibility that early management of eczema may reduce the prevalence of sensitization in children. PMID- 17845410 TI - Exhaled nitric oxide and biomarkers in exhaled breath condensate indicate the presence, severity and control of childhood asthma. AB - BACKGROUND: Exhaled nitric oxide and inflammatory biomarkers in exhaled breath condensate may be useful to diagnose and monitor childhood asthma. Their ability to indicate an asthma diagnosis, and to assess asthma severity and control, is largely unknown. OBJECTIVE: To study (1) the ability of exhaled nitric oxide and inflammatory markers in exhaled breath condensate (nitrite, nitrate, hydrogen peroxide, 8-isoprostane, IFN-gamma, TNF-alpha, IL-2, -4, -5, -10 and acidity) to discriminate between childhood asthma and controls. (2) The ability of these biomarkers to indicate asthma severity and control. METHODS: One-hundred and fourteen children were included: 64 asthmatics (10.7+/-3.0 years, 67.2% atopic) and 50 controls (10.0+/-0.4 years). Condensate was collected using a glass condenser. RESULTS: Exhaled nitric oxide, IFN-gamma and IL-4 in exhaled breath condensate differed significantly between asthma and controls. Multivariate backward logistic regression models demonstrated that IL-4 (odds ratio 7.9, 95% confidence interval 1.2-51.0) was the only significant indicator of an asthma diagnosis. Asthma control was best assessed by exhaled nitric oxide, 8 isoprostane, IFN-gamma and IL-4 (sensitivity 82%, specificity 80%, P<0.05), whereas exhaled nitric oxide, 8-isoprostane, nitrate and nitrite in condensate were the best indicators of asthma severity (sensitivity 89%, specificity 72%, P<0.05). CONCLUSION: Different markers in condensate are of an additional value to exhaled nitric oxide, and are needed in non-invasive inflammometry. They could be useful to diagnose asthma and to indicate asthma control and severity in childhood. PMID- 17845411 TI - Effects of air pollution on asthma hospitalization rates in different age groups in Hong Kong. AB - AIMS: To assess the relationship between levels of ambient air pollutants and hospitalization rates for asthma in Hong Kong (HK). METHODS: This is a retrospective ecological study. Data of daily emergency hospital admissions to 15 major hospitals in HK for asthma and indices of air pollutants [sulphur dioxide (SO(2)), nitrogen dioxide (NO(2)), ozone (O(3)), particulates with an aerodynamic diameter of <10 microm particulate matter (PM(10)) and 2.5 microm (PM(2.5))] and meteorological variables from January 2000 to December 2005 were obtained from several government departments. Analysis was performed by the generalized additive models with Poisson distribution. The effects of time trend, season, other cyclical factors, temperature and humidity were adjusted. Autocorrelation and overdispersion were corrected. RESULTS: Altogether, 69 716 admissions were assessed. Significant associations were found between hospital admissions for asthma and levels of NO(2), O(3), PM(10) and PM(2.5). The relative risks (RR) for hospitalization for every 10 microg/m(3) increase in NO(2), O(3), PM(10) and PM(2.5) were 1.028, 1.034, 1.019 and 1.021, respectively, at a lag day that ranged from cumulative lag 0-4 to 0-5. In a multi-pollutant model, O(3) was significantly associated with increased admissions for asthma. The younger age group (0-14 years) tended to have a higher RR for each 10 microg/m(3) increase in pollutants than those aged 15-65 years. The elderly (aged >/=65 years) had a shorter 'best' lag time to develop asthma exacerbation following exposure to pollutants than those aged <65 years. CONCLUSION: Adverse effects of ambient concentrations of air pollutants on hospitalization rates for asthma are evident. Measures to improve air quality in HK are urgently needed. PMID- 17845412 TI - Familial risks for asthma among twins and other siblings based on hospitalizations in Sweden. AB - BACKGROUND: Asthma is a common disabling condition, with known environmental and familial risk factors and with their assumed interactions. We wanted to carry out a family study on asthma to address gene-environment interactions at a population level. METHODS: We conducted a nation-wide study on familial risks for asthma. An asthma database was constructed by linking the Multigeneration Register on 0-72 year-old subjects to the Hospital Discharge Register for diagnosed asthma cases in Sweden from years 1987 to 2004. Standardized incidence ratios (SIRs) were calculated for affected singleton siblings, twins and spouses by comparing with those whose siblings or spouses had no asthma. RESULTS: A total of 67 370 hospitalized cases and 5638 affected siblings were identified with a familial SIR of 3.70, which was independent of sex, diagnostic age and age differences between the siblings. The SIR for different-sex twins was 5.17 and for same-sex twins it was 13.38. There was a low correlation between spouses for asthma. CONCLUSIONS: Asthma shows a higher familial risk than many common diseases. The higher difference in familial excess risk between singleton siblings and different-sex twins provides strong genetic epidemiological evidence for gene-environment interactions in asthma. The concept of gene-environment interactions needs to be accommodated in future aetiological studies on asthma. Data on environmental factors and family history are important for clinical risk estimation. PMID- 17845413 TI - Prevalence and severity of asthma and allergies in schoolchildren in Lhasa, Tibet. AB - BACKGROUND: The International Study of Asthma and Allergies in Childhood (ISAAC) demonstrated that large variations existed in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis and eczema throughout the world and that environmental factors and lifestyle customs are major determinants of the prevalence and severity of these diseases. However, the relevant data about children living at high-altitude locations were considered to be underreported. OBJECTIVE: The ISAAC Phase III programme was carried out in Lhasa, the Tibetan Autonomous Region in China, at an elevation of 3658 m above sea level to examine the occurrence of asthma, allergic rhinoconjunctivitis and eczema in schoolchildren aged 13-14 years. METHODS: All 3196 schoolchildren in eight public junior high schools in urban Lhasa who were confirmed to be 13-14 years old were invited and participated in both written and video questionnaire investigations, among which 3190 pieces of data (49.8% of boys and 50.2% of girls) were validated and analysed. RESULTS: Among the overall observations, the prevalence of 'having ever experienced wheezing', 'current wheezing' and 'diagnosed to have asthma' was 1.4%, 0.8% and 1.1%, respectively. The prevalence of current exercise-induced asthma and current nocturnal cough was 7.1% and 4.6%, respectively. The current prevalence of allergic rhinoconjunctivitis and eczema was 5.2% and 0.4%, respectively. In addition, the prevalence of rhinoconjunctivitis symptoms during the past 12 months showed no discernable differences throughout the year. CONCLUSION: The prevalence of asthma, allergic rhinoconjunctivitis and eczema over the past 12 months was the lowest among the centres, that performed ISAAC worldwide. PMID- 17845414 TI - Mannose binding lectin gene polymorphisms and asthma. AB - BACKGROUND: Bronchial asthma is a chronic inflammatory disorder of the airways. Recently, it has been suggested that complement plays significant roles in asthma. Mannose-binding lectin (MBL) is one of the key molecules in complement activation pathways that are associated with several infectious and immune disorders. SUBJECTS AND METHOD: To investigate whether MBL plays roles in asthma, we analysed MBL2 polymorphisms (allele B, H/L and Y/X) and plasma MBL levels in a Japanese adult population including 232 healthy controls and 579 asthmatics. RESULTS: Although there was linkage disequilibrium among the three polymorphisms, each polymorphism significantly affects serum MBL levels independently. However, there were no significant differences between asthmatics and controls in MBL2 genotype distribution and in MBL concentrations [1.47+/-0.07(SE) mg/L for asthmatics and 1.66+/-0.14 mg/L for controls, P=0.2]. MBL levels and genotype have no significant relationship with serum IgE, pulmonary functions, and the severity of asthma. CONCLUSION: Although plasma MBL levels depend on the MBL2 polymorphisms, these polymorphisms and plasma MBL levels are not associated with the asthma phenotype. PMID- 17845415 TI - Kiwifruit allergy: actinidin is not a major allergen in the United Kingdom. AB - BACKGROUND: Actinidin has previously been reported as the major allergen in kiwifruit. Objectives To investigate the relevance of actinidin in a well characterized population of UK patients with kiwifruit allergy. METHODS: To identify the allergens in kiwifruit, using Western blots, we examined the IgE binding patterns of 76 patients with a history of kiwifruit allergy, 23 of who had had a positive double-blind, placebo-controlled food challenge. In addition, IgE binding to purified native actinidin was studied in 30 patients, and to acidic and basic isoforms of recombinant actinidin in five patients. Inhibition of IgE binding to kiwifruit protein extract by purified native actinidin was investigated by both inhibition immunoblots and inhibition ELISAs using pooled sera. RESULTS: Twelve protein bands in kiwifruit protein extract were bound by IgE. A protein band with a molecular weight of 38 kDa was the major allergen recognized by 59% of the population. IgE did not bind to actinidin in the kiwifruit protein extract, or to purified native or recombinant forms of actinidin during Western blotting. Pooled sera bound to kiwifruit protein extract but not purified actinidin on ELISA, and pre-incubating sera with actinidin did not inhibit IgE binding to kiwifruit protein extract on immunoblot or ELISA. CONCLUSION: A novel 38 kDa protein, not actinidin, is the major allergen in this large study population. Identification of major allergens in one patient group is therefore not necessarily reproducible in another; therefore, major allergens should not be defined until there is a sufficient body of data from diverse geographical and cultural populations. PMID- 17845416 TI - Percutaneous reactivity to natural rubber latex proteins persists in health-care workers following avoidance of natural rubber latex. AB - BACKGROUND: Long-term avoidance of natural rubber latex [Hevea brasiliensis (Hev b)] is currently recommended for health-care workers (HCWs) with established natural rubber latex (NRL) allergy. Percutaneous sensitivity to eight Hev b NRL allergens was evaluated in HCWs in 2000. To date, no studies have evaluated the longitudinal effects of NRL avoidance on percutaneous sensitivity to NRL allergens. OBJECTIVE: The aims of this study were to evaluate changes in percutaneous reactivity to non-ammoniated latex (NAL) and NRL allergens in HCWs 5 years after a recommendation to avoid NRL and to evaluate factors that predict the persistence of in vivo sensitivity to NAL and NRL allergens. METHODS: Skin prick testing was performed with NAL, seven NRL allergens (Hev b 1, 2, 3, 4, 6.01, 7.01, and 13), and recombinant Hev b 5 (rHev b 5) in 34 HCWs who were initially evaluated in 2000 for occupationally related NRL allergy. Serial 10 fold dilutions of NAL and NRL allergens were employed in skin testing. Sera from the HCWs were assayed for latex and enhanced latex (rHev b 5-enriched allergosorbent)-specific IgE antibodies using the ImmunoCAP assay. RESULTS: The prevalence of work-related symptoms significantly decreased between 2000 and 2005 with avoidance of NRL (P<0.05). A >/=100-fold reduction in percutaneous sensitivity to Hev b 2 and Hev b 7 was less likely in those with prior history of systemic reactions to NRL (P=0.0053), reported history of reaction to cross reactive foods (P=0.014), continued local reactions to NRL gloves (P<0.0001), or high NRL glove exposure since the initial study (P=0.0075). The diagnostic sensitivity and specificity of the latex-specific IgE serology was 54% and 87.5%, respectively, in comparison with NAL skin tests. The addition of rHev b 5 to the ImmunoCAP (enhanced latex) allergosorbent altered the diagnostic sensitivity and specificity of the ImmunoCAP to 77% and 75%, respectively. CONCLUSION: While symptoms may resolve quickly with NRL avoidance therapy, detectable IgE indicating continued sensitization remains beyond 5 years, and thus continued avoidance of NRL should be recommended. PMID- 17845418 TI - Regulation of German cockroach extract-induced IL-8 expression in human airway epithelial cells. AB - BACKGROUND: Cockroaches have been known as a cause of respiratory allergies such as asthma. IL-8 plays an integral role in the coordination and persistence of the inflammatory process in the chronic inflammation of the airways in asthma. OBJECTIVE: We investigated the mechanism by which German cockroach extract (GCE) triggers IL-8 release from human airway epithelial cells. METHODS: Chemical inhibitors were pretreated before addition of GCE for promoter activity and protein synthesis of IL-8. The Transcriptional activity of IL-8 promoter was analysed by mutational, deletional anaylsis and electrophoretic mobility shift assay (EMSA). RESULTS: Stimulation of H292 cells with GCE resulted in a time- and concentration-dependent induction of IL-8 transcription and protein synthesis. IL 8 promoter deletion analysis indicated that position -132 to +41 was essential for GCE-induced IL-8 transcription, and mutants with substitutions in activator protein (AP)-1, nuclear factor (NF)-IL6 and NF-kappaB-binding sites revealed a requirement for NF-kappaB and NF-IL6, but not AP-1, in GCE-induced activation of the IL-8 promoter. The DNA-binding activities of NF-kappaB and NF-IL6 were induced by GCE, as determined by EMSA. The chemical inhibition of extracellular signal-regulated kinase (ERK) attenuated GCE-induced transcriptional activity and protein synthesis. In addition, through aprotinin treatment and PAR2 small interfering RNA transfection, it was proven that protease of GCE is consistent with the regulation of GCE-induced IL-8. CONCLUSION: We conclude that GCE with protease activity-induced IL-8 expression is regulated by transcriptional activation of NF-kappaB and NF-IL6 coordinating with the ERK pathway in human airway epithelial cells. PMID- 17845417 TI - Distinctive immunoglobulin E anti-house dust allergen-binding specificities in a tropical Australian Aboriginal community. AB - BACKGROUND: There is evidence that the specificity of the IgE binding in allergy tests can vary for different populations. OBJECTIVE: We aimed to examine the allergenic specificity of IgE binding in sera from house dust mite (HDM)-atopic subjects in a tropical Australian Aboriginal community. METHODS: Sera shown to contain IgE antibodies to an HDM extract of Dermatophagoides pteronyssinus were examined for IgE binding to a panel of nine purified HDM allergens from this mite species by quantitative microtitre assays. IgG antibody binding (IgG1 and IgG4) was also measured. RESULTS: The IgE-binding activity in the sera from the Aboriginal community was not directed to the expected major groups 1 and 2 HDM allergens but instead to the group 4 amylase allergen. There was also little IgE binding to the potentially cross-reactive tropomyosin (Der p 10) or arginine kinase (Der p 20) allergens. The IgG4 antibody was rarely detected and limited to the Der p 4 allergen. IgG1 antibody binding was frequently measured to all the allergens regardless of an individual's atopic status, whereas in urban communities it is restricted to the major allergens and to atopic subjects. CONCLUSION: The high IgE anti-HDM response of Australian Aboriginals predominantly bound Der p 4 and not the Der p 1 and 2 allergens, showing a distinctive allergy that could affect the disease outcome and diagnosis. PMID- 17845419 TI - CD137 ligand prevents the development of T-helper type 2 cell-mediated allergic asthma by interferon-gamma-producing CD8+ T cells. AB - BACKGROUND: Allergic asthma is a T-helper type 2 (Th2) cell-mediated chronic disease that is characterized by airway hyperreactivity (AHR) and chronic eosinophilic airway inflammation. Several studies suggest co-stimulatory molecules like CD137 as potential targets for therapeutic interventions in allergic airway disease. Recently, we could show in a murine asthma model that administration of an agonistic antibody against the receptor of the co stimulatory molecule CD137 prevented and even reversed an already-established asthma phenotype. OBJECTIVE: The purpose of this study was to analyse the effect of stimulation of the CD137 ligand by a monoclonal antibody (CD137L mAb). METHODS: To induce an asthma-like phenotype, BALB/c mice were sensitized to ovalbumin (OVA), followed by an intrapulmonary allergen challenge. Anti-CD137L or control mAb were applied 1 day before OVA immunization or after the asthma phenotype was already established. RESULTS: Stimulation of the CD137L instead of the receptor by CD137L mAb prevents the development of an asthma-like phenotype but does not reverse established disease. While the receptor-mediated effect is partly mediated by anergy of CD4(+) T cells and partly by induction of IFN-gamma producing CD8(+) T cells, the effect of the CD137L mAb is completely dependent on IFN-gamma-producing CD8(+) T cells: blockade of IFN-gamma and depletion of CD8(+) T cells fully abrogated the observed protective effect. In vitro experiments showed that the anti-CD137L mAb ligates directly to CD8(+) T cells and induces the generation of IFN-gamma by this cell population. CONCLUSION: Our results demonstrate that anti-CD137L mAb prevents disease development via IFN-gamma producing CD8(+) T cells but is inferior to stimulation of the receptor that reverses established disease by a mechanism including CD4(+) T cell anergy. PMID- 17845420 TI - Cell type-specific regulation of brain-derived neurotrophic factor in states of allergic inflammation. AB - BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a molecule influencing neuronal proliferation and differentiation. In states of allergy, it may orchestrate inflammatory changes by linking the immune system with the nervous system. Because the precise regulation of gene transcription in mast cells MCs is not clear, the present studies assessed the gene regulation of BDNF in this inflammatory cell type. METHODS: Transcriptional expression of BDNF in human skin was studied in isolated cells using RT-PCR. In situ lesional MC BDNF protein expression was analysed by immunohistochemistry and related to the differential staining of MCs and functional effects of BDNF on HaCaT keratinocytes. RESULTS: BDNF mRNA expression was found in isolated human skin MCs, keratinocytes, and fibroblasts. Also, low levels were found in endothelial cells and melanocytes. BDNF protein expression was found in situ in lesional and non-lesional MCs. A significantly decreased expression of BDNF protein was found in atopic dermatitis lesional MCs when compared with control MC expression. Functional in vitro experiments demonstrated that a decrease in BDNF stimulation led to increased secretion rates for stem cell factor and IL-8 in HaCaT keratinocytes. CONCLUSION: The demonstration of a decreased level of BDNF gene transcription in lesional MCs points to a differential regulation of MC-released neutrotrophins in cutaneous allergic inflammation. Topically administered neurotrophin receptor-modulating compounds should be receptor target specific and not universally acting in diseases such as atopic dermatitis or allergic asthma. PMID- 17845422 TI - A protocol for generating high numbers of mature and functional human mast cells from peripheral blood. AB - BACKGROUND: Mast cells (MCs) are multi-functional effector cells with an essential role in innate immunity and host defence, and under several pathological conditions, such as allergy. Here, we aimed at defining the culture conditions that would allow efficient generation of mature and functional human MCs from their progenitor cells. METHODS: Human peripheral blood-derived CD34(+) progenitor cells were cultured in vitro under serum-free conditions with human stem cell factor for 9 weeks. Growth and differentiation of the cells into MCs were optimized by selected cytokines and a combination of hypoxic and normoxic conditions. MCs were phenotypically characterized by immunocytochemistry, their preformed mediators were quantified, and their functional ability to degranulate and release histamine was tested. RESULTS: On average, 20 x 10(6) mature MCs were generated from 0.5 x 10(6) progenitor cells during 9 weeks of culture, i.e. at least a 40-fold increase in cell number was achieved. The mature MCs had oval shaped non-lobular nuclei, contained histamine, heparin, tryptase, chymase, and cathepsin G in their secretory granules, and strongly expressed c-kit (CD117) and Fc epsilon receptor I on their surface. Histamine release from the cells could be brought about by IgE-anti-IgE cross-linkage, compound 48/80, substance P, and anaphylatoxin C3a. The MCs remained functional for several weeks after their maturation. CONCLUSION: This study describes an efficient protocol for generating mature MCs from human peripheral blood with a functional phenotype of connective tissue-type MCs. Use of these cultured human MCs will increase our knowledge and understanding about human MC development and biology in human disease. PMID- 17845421 TI - Effect of ageing on pulmonary inflammation, airway hyperresponsiveness and T and B cell responses in antigen-sensitized and -challenged mice. AB - BACKGROUND: The effect of ageing on several pathologic features of allergic asthma (pulmonary inflammation, eosinophilia, mucus hypersecretion), and their relationship with airway hyperresponsiveness (AHR) is not well characterized. OBJECTIVE: To evaluate lung inflammation, mucus metaplasia and AHR in relationship with age in murine models of allergic asthma comparing young and older mice. METHODS: Young (6 weeks) and older (6, 12, 18 months) BALB/c mice were sensitized and challenged with ovalbumin (OVA). AHR and bronchoalveolar fluid (BALF), total inflammatory cell count and differential were measured. To evaluate mucus metaplasia, quantitative PCR for the major airway mucin-associated gene, MUC-5AC, from lung tissue was measured, and lung tissue sections stained with periodic acid-Schiff (PAS) for goblet-cell enumeration. Lung tissue cytokine gene expression was determined by quantitative PCR, and systemic cytokine protein levels by ELISA from spleen-cell cultures. Antigen-specific serum IgE was determined by ELISA. RESULTS: AHR developed in both aged and young OVA sensitized/challenged mice (OVA mice), and was more significantly increased in young OVA mice than in aged OVA mice. However, BALF eosinophil numbers were significantly higher, and lung histology showed greater inflammation in aged OVA mice than in young OVA mice. MUC-5AC expression and numbers of PAS+ staining bronchial epithelial cells were significantly increased in the aged OVA mice. All aged OVA mice had increased IL-5 and IFN-gamma mRNA expression in the lung and IL 5 and IFN-gamma protein levels from spleen cell cultures compared with young OVA mice. OVA-IgE was elevated to a greater extent in aged OVA mice. CONCLUSIONS: Although pulmonary inflammation and mucus metaplasia after antigen sensitization/challenge occurred to a greater degree in older mice, the increase in AHR was significantly less compared with younger OVA mice. Antigen treatment produced a unique cytokine profile in older mice (elevated IFN-gamma and IL-5) compared with young mice (elevated IL-4 and IL-13). Thus, the airway response to inflammation is lessened in ageing animals, and may represent age-associated events leading to different phenotypes in response to antigen provocation. PMID- 17845423 TI - Hawksbill sea turtles: can phylogenetics inform harvesting? PMID- 17845426 TI - How King et al. (2006) define an 'evolutionary distinction' of a mouse subspecies: a response. PMID- 17845427 TI - Inferences on the population structure and colonization process of the invasive oriental fruit fly, Bactrocera dorsalis (Hendel). AB - The phytophagous insects of the Tephritidae family offer different case histories of successful invasions. An example is Bactrocera dorsalis sensu stricto, the oriental fruit fly which has been recognized as a key pest of Asia and the Pacific. It is known to have the potential to establish adventive populations in various tropical and subtropical areas. Despite the economic risk associated with a putative stable presence of this fly, the genetic aspects of its invasion process have remained relatively unexplored. Using microsatellite markers we have investigated the population structure and genetic variability in 14 geographical populations across the four areas of the actual species range: Far East Asia, South Asia, Southeast Asia and the Pacific Area. Results of clustering and admixture, associated with phylogenetic and migration analyses, were used to evaluate the changes in population genetic structure that this species underwent during its invasion process and establishment in the different areas. The colonization process of this fly is associated with a relatively stable population demographic structure, especially in an unfragmented habitat, rich in intensive cultivation such as in Southeast Asia. In this area, the results suggest a lively demographic history, characterized by evolutionary recent demographic expansions and no recent bottlenecks. Cases of genetic isolation attributable to geographical factors, fragmented habitats and/or fruit trade restrictions were observed in Bangladesh, Myanmar and Hawaii. Regarding the pattern of invasion, the overall genetic profile of the considered populations suggests a western orientated migration route from China to the West. PMID- 17845428 TI - Two alternate mechanisms contribute to the persistence of interdependent lineages in Pogonomyrmex harvester ants. AB - Some populations of Pogonomyrmex harvester ants comprise pairs of highly differentiated lineages with queens mating at random with several males of their own and of the alternate lineage. These queens produce two types of diploid offspring, those fertilized by males of the queens' lineage which develop into new queens and those fertilized by males of the other lineage which mostly develop into functionally sterile workers. This unusual mode of genetic caste determination has been found in 26 populations and a total of four lineage pairs (F(1)-F(2), G(1)-G(2), H(1)-H(2) and J(1)-J(2)) have been described in these populations. Despite the fact that a few interlineage queens are produced, previous studies revealed that there is a complete lack of genetic introgression between lineages. Here we quantify the proportion of interlineage queens produced in each of the four lineage pairs and determine the fate of these queens. In the F(1)-F(2), G(1)-G(2) and H(1)-H(2) lineage pairs, interlineage queens were produced by a minority of colonies. These colonies exclusively produced interlineage queens and workers, suggesting that interlineage eggs can develop into queens in these three pairs of lineages in the absence of competition with pure-lineage brood. An analysis of three key stages of the colony life cycle revealed that colonies headed by interlineage queens failed to grow sufficiently to produce reproductive individuals. In laboratory comparisons, interlineage queens produced fewer viable eggs, with the effect that they raised fewer workers and lost more weight per worker produced than pure-lineage queens. In the J(1) J(2) lineage pair, we did not find a single interlineage queen, raising the possibility that interlineage eggs have completely lost the ability to develop into queens in this lineage pair. Hence, two distinct mechanisms seem to account for the complete lack of between-lineage gene flow in the F(1)-F(2), G(1)-G(2), H(1)-H(2) and J(1)-J(2) lineage pairs. PMID- 17845429 TI - Genetic diversity in diploid vs. tetraploid Rorippa amphibia (Brassicaceae). AB - The frequency of polyploidy increases with latitude in the Northern Hemisphere, especially in deglaciated, recently colonized areas. The cause or causes of this pattern are largely unknown, but a greater genetic diversity of individual polyploid plants due to a doubled genome and/or a hybrid origin is seen as a likely factor underlying selective advantages related to life in extreme climates and/or colonization ability. A history of colonization in itself, as well as a recent origin, and possibly a limited number of polyploidization events would all predict less genetic diversity in polyploids than in diploids. The null hypothesis of higher gene diversity in polyploids has to date hardly been quantified and is here tested in self-incompatible Rorippa amphibia (Brassicaceae). The species occurs in diploid and tetraploid forms and displays clear geographical polyploidy in Europe. On the basis of eight microsatellite loci it can be concluded that the level of gene diversity is higher in tetraploids than in diploids, to an extent that is expected under neutral evolution when taking into account the larger effective population size in the doubled cytotype. There is thus no evidence for reduced genetic diversity in the tetraploids. The evidence presented here may mean that the tetraploids' origin is not recent, has not been affected by bottlenecks and/or that tetraploids were formed multiple times while an effect of introgression may also play a role. PMID- 17845430 TI - Genetic architecture in codling moth populations: comparison between microsatellite and insecticide resistance markers. AB - The codling moth, Cydia pomonella, is renowned for developing resistance to insecticides and causing significant economic damage to pome fruits worldwide. In spite of its economic importance, little is known about the patterns of movement of this pest and the effects of insecticide treatment on the population genetic structure. Here, we investigated the genetic structure of the pest in 27 orchards from France, Italy, Armenia and Chile at seven microsatellite loci and two resistance markers [biochemical activity of cytochrome P450 oxidases and proportion of knockdown resistance (kdr) alleles in the sodium channel gene]. According to the microsatellite loci, we detected isolation by distance at the supranational scale but found no evidence of geographical structure among the 24 French orchards, which were mainly structured by the intensity of the insecticide treatments. Similarly, the highest levels of metabolic resistance associated with activity of the cytochrome P450 oxidases were detected in the most treated orchards. The kdr alleles were observed in southern France and Armenia where the pyrethroid insecticides were or have been intensively sprayed. The intensity of the insecticide treatments marginally affected the allelic richness in each orchard, but not the level of inbreeding. These results suggest important and high-distance gene flow among the codling moth populations, which were mainly structured according to the history of insecticide applications. Differences in mutation-migration-drift equilibrium among treated and untreated orchards also suggest that insecticide applications are the main force regulating the local dynamics of codling moth populations. PMID- 17845431 TI - Patterns of genetic diversity in outcrossing and selfing populations of Arabidopsis lyrata. AB - Arabidopsis lyrata is normally considered an obligately outcrossing species with a strong self-incompatibility system, but a shift in mating system towards inbreeding has been found in some North American populations (subspecies A. lyrata ssp. lyrata). This study provides a survey of the Great Lakes region of Canada to determine the extent of this mating system variation and how outcrossing rates are related to current population density, geographical distribution, and genetic diversity. Based on variation at microsatellite markers (progeny arrays to estimate multilocus outcrossing rates and population samples to estimate diversity measures) and controlled greenhouse pollinations, populations can be divided into two groups: (i) group A, consisting of individuals capable of setting selfed seed (including autogamous fruit set in the absence of pollinators), showing depressed outcrossing rates (T(m) = 0.2-0.6), heterozygosity (H(O) = 0.02-0.06) and genetic diversity (H(E) = 0.08-0.10); and (ii) group B, consisting of individuals that are predominantly self-incompatible (T(m) > 0.8), require pollinators for seeds set, and showing higher levels of heterozygosity (H(O) = 0.13-0.31) and diversity (H(E) = 0.19-0.410). Current population density is not related to the shift in mating system but does vary with latitude. Restricted gene flow among populations was evident among all but two populations (F(ST) = 0.11-0.8). Group A populations were more differentiated from one another (F(ST) = 0.78) than they were from group B populations (F(ST) = 0.59), with 41% of the variation partitioned within populations, 47% between populations, and 12% between groups. No significant relationship was found between genetic and geographical distance. Results are discussed in the context of possible postglacial expansion scenarios in relation to loss of self incompatibility. PMID- 17845432 TI - Identifying the early genetic consequences of habitat degradation in a highly threatened tropical conifer, Araucaria nemorosa Laubenfels. AB - The early genetic effects of habitat degradation were investigated in the critically endangered conifer Araucaria nemorosa. This species occurs in New Caledonia, a global biodiversity hotspot where the world's greatest concentration of endemic conifer species coincides with an extremely high level of habitat destruction due to fire and mining. Using seven microsatellite loci, estimates were made of genetic marker variation, inbreeding coefficients and population differentiation of adult and seedling cohorts of A. nemorosa. These were contrasted with equivalent estimates, made over similar spatial scales and with the same marker loci, in the locally common and more widespread sister species Araucaria columnaris. There were no significant differences in population genetic parameters between adult populations of the two species, despite their different abundances. However, in A. nemorosa, the juvenile cohort showed a loss of rare alleles and elevated levels of inbreeding when compared to the adult cohort. These genetic differences between the cohorts were not observed in the locally common A. columnaris. This suggests that recent environmental degradation is influencing the genetic structure of A. nemorosa populations. Although this is not detectable among predisturbance adult populations, an early warning of these impacts is evident in more recently established seedling cohorts. The conservation implications of these results are discussed. PMID- 17845433 TI - Genetic divergence in the Atlantic-Mediterranean Montagu's blenny, Coryphoblennius galerita (Linnaeus 1758) revealed by molecular and morphological characters. AB - Coryphoblennius galerita is a small intertidal fish with a wide distribution and limited dispersal ability, occurring in the northeastern Atlantic and Mediterranean. In this study, we examined Atlantic and Mediterranean populations of C. galerita to assess levels of genetic divergence across populations and to elucidate historical and contemporary factors underlying the distribution of the genetic variability. We analyse three mitochondrial and one nuclear marker and 18 morphological measurements. The combined dataset clearly supports the existence of two groups of C. galerita: one in the Mediterranean and another in the northeastern Atlantic. The latter group is subdivided in two subgroups: Azores and the remaining northeastern Atlantic locations. Divergence between the Atlantic and the Mediterranean can be the result of historical isolation between the populations of the two basins during the Pleistocene glaciations. Present-day barriers such as the Gibraltar Strait or the 'Almeria-Oran jet' are also suggested as responsible for this isolation. Our results show no signs of local extinctions during the Pleistocene glaciations, namely at the Azores, and contrast with the biogeographical pattern that has been observed for Atlantic Mediterranean warm-water species, in which two groups of populations exist, one including the Mediterranean and the Atlantic coast of western Europe, and another encompassing the western tropical coast of Africa and the Atlantic islands of the Azores, Madeira and Canaries. Species like C. galerita that tolerate cooler waters, may have persisted during the Pleistocene glaciations in moderately affected locations, thus being able to accumulate genetic differences in the more isolated locations such as the Azores and the Mediterranean. This study is one of the first to combine morphological and molecular markers (mitochondrial and nuclear) with variable rates of molecular evolution to the study of the relationships of the Atlantic and Mediterranean populations of a cool-water species. PMID- 17845434 TI - Glacial refugia and recolonization pathways in the brown seaweed Fucus serratus. AB - The last glacial maximum (20,000-18,000 years ago) dramatically affected extant distributions of virtually all northern European biota. Locations of refugia and postglacial recolonization pathways were examined in Fucus serratus (Heterokontophyta; Fucaceae) using a highly variable intergenic spacer developed from the complete mitochondrial genome of Fucus vesiculosus. Over 1,500 samples from the entire range of F. serratus were analysed using fluorescent single strand conformation polymorphism. A total of 28 mtDNA haplotypes was identified and sequenced. Three refugia were recognized based on high haplotype diversities and the presence of endemic haplotypes: southwest Ireland, the northern Brittany Hurd Deep area of the English Channel, and the northwest Iberian Peninsula. The Irish refugium was the source for a recolonization sweep involving a single haplotype via northern Scotland and throughout Scandinavia, whereas recolonization from the Brittany-Hurd Deep refugium was more limited, probably because of unsuitable soft-bottom habitat in the Bay of Biscay and along the Belgian and Dutch coasts. The Iberian populations reflect a remnant refugium at the present-day southern boundary of the species range. A generalized skyline plot suggested exponential population expansion beginning in the mid-Pleistocene with maximal growth during the Eems interglacial 128,000-67,000 years ago, implying that the last glacial maximum mainly shaped population distributions rather than demography. PMID- 17845435 TI - Population structure and species boundary delimitation of cryptic Dioryctria moths: an integrative approach. AB - Accurate delimitation of species boundaries is especially important in cryptic taxa where one or more character sources are uninformative or are in conflict. Rather than relying on a single marker to delimit species, integrative taxonomy uses multiple lines of evidence such as molecular, morphological, behavioural and geographic characters to test species limits. We examine the effectiveness of this approach by testing the delimitation of two cryptic Nearctic species of Dioryctria (Lepidoptera: Pyralidae) using three independent molecular markers [cytochrome c oxidase I (COI), second internal transcribed spacer unit (ITS2), and elongation factor 1alpha (EF1alpha)], forewing variation and larval host plant association. Although mitochondrial DNA (mtDNA) haplotypes do not form reciprocally monophyletic clades, restricted gene flow between COI haplotype groups, and concordance with ITS2 genotypes, forewing variation and host plant associations support delimitation of two Nearctic species: eastern Dioryctria reniculelloides and western Dioryctria pseudotsugella. Conversely, EF1alpha genotype variation was incongruent with the two previous markers. A case of discordance between COI and ITS2 was detected, suggesting either introgression due to hybridization or retained ancestral polymorphism due to incomplete coalescence. This study is consistent with other similar literature where molecular loci in closely related species progress from shared to fixed haplotypes/alleles, and from polyphyletic to reciprocally monophyletic relationships, although loci may vary in these characteristics despite maintenance of genomic integrity between distinct species. In particular, mtDNA in other studies generally showed a lower rate of fixation of differences than did X-linked or autosomal loci, reinforcing the need to use an integrative approach for delimiting species. PMID- 17845437 TI - Cryptic differentiation in alpine-endemic, high-altitude butterflies reveals down slope glacial refugia. AB - The influence of cyclic climate fluctuations and their impact on high-altitude species is still insufficiently understood. We therefore analysed in this study the genetic structure of cold-adapted animals and their coherence with geographical distributions throughout the Late Quaternary. We analysed 588 individuals from 23 populations of the alpine-endemic lesser mountain ringlet, Erebia melampus, by allozyme electrophoresis to detect its intraspecific differentiation. As an outgroup, we added one population of Erebia sudetica inalpina from Grindelwald (Swiss Alps). Seventeen of 18 loci were polymorphic. The mean F(ST) over all samples was 37%. We detected strong differentiation into three lineages with the genetic distances between the two E. melampus groups being larger than between each of the two E. melampus groups and E. sudetica. The mean genetic distance among these three groups was 0.17. These results give evidence for the existence of a species complex within the E. melampus/sudetica group and indicate a discontinuous distribution within this group during at least the last ice age. One of them, E. sudetica inalpina, is found in the northern Alps and most probably had its Wurm glacial refugium north of the glaciated Alps. The western E. melampus group might have had a refugium at the southwestern Alps margin, the eastern group in the lower altitudes of the southeastern and/or eastern Alps. In the latter, a further subdivision within this relict area is possible. PMID- 17845436 TI - Ancient differentiation in the single-island avian radiation of endemic Hispaniolan chat-tanagers (Aves: Calyptophilus). AB - The simple geographic structure of island systems often makes them tractable for studies of the patterns and processes of biological diversification. The Calyptophilus chat-tanagers of Hispaniola are of general evolutionary interest because their multiple lineages might have arisen on a single island, of conservation concern because several isolated populations are nearly extinct, and taxonomically ambiguous because they have been variously lumped or split into one to four species. To explore the context of diversification of the seven extant Calyptophilus populations, we conducted a multilocus coalescent analysis based on sequences of mitochondrial ND2 and three nuclear intron loci. We then compared patterns of phylogeographic genetic variation with the morphological differences that distinguish these populations. Mitochondrial haplotypes formed two reciprocally monophyletic groups separated by a large magnitude of nucleotide divergence. Intron structure largely paralleled the geographic grouping pattern of the mitochondrial DNA (mtDNA), but these groups were only reciprocally monophyletic at one of the three introns. Also, the magnitude of between-group divergence was much lower in the introns than mtDNA genealogies. Multilocus coalescent analyses inferred a nonzero divergence time between these two major geographic groups, but suggested that they have experienced a low level of gene flow. All four markers showed substantial allele sharing within each of the two groups, demonstrating that many now separated montane populations do not have long histories of isolation. Considered in concert, our multilocus phylogeographic reconstructions support the recognition of two species within the Calyptophilus complex, and raise the possibility that these taxa differentiated prior to the fusion of the two palaeo-islands that form present-day Hispaniola. PMID- 17845438 TI - Kin structure provides no explanation for intruders in social aphids. AB - Nontraditional social organisms have received increasing attention in recent years, because they present opportunities to study the convergent properties of social evolution. Some aphid species are social, occurring in dense clones with specialized morphs that attack predators and parasites. Little is known about how social aphid colonies resolve conflicts of interest when clonal barriers break down. Pemphigus obesinymphae is a North American gall-forming social aphid that produces both nymphal defenders that protect natal clones, and specialized intruders that invade other nearby clones on their host plants. We tested the hypothesis that clones are arranged on their host plants in spatial clusters of related family groups, such that intruders would be biased towards movement within kin groups. Movement within and not between kin groups would then provide insight into the nature of conflict in this social aphid. We sampled eight sites in the eastern United States and in Arizona, and used eight microsatellite markers to estimate pairwise relatedness between spatial groups. We found little evidence of deviation from random distributions of genotypes on their host plants. Evidently, Pem. obesinymphae intruders typically exploit unrelated clones, and spatial orientation provides no solution to the problem of 'polyclonality' in this species. We discuss implications of this result for our understanding of cooperation and conflict in social aphids. PMID- 17845439 TI - Are clownfish groups composed of close relatives? An analysis of microsatellite DNA variation in Amphiprion percula. AB - A central question of evolutionary ecology is: why do animals live in groups? Answering this question requires that the costs and benefits of group living are measured from the perspective of each individual in the group. This, in turn, requires that the group's genetic structure is elucidated, because genetic relatedness can modulate the individuals' costs and benefits. The clown anemonefish, Amphiprion percula, lives in groups composed of a breeding pair and zero to four nonbreeders. Both breeders and nonbreeders stand to gain by associating with relatives: breeders might prefer to tolerate nonbreeders that are relatives because there is little chance that relatives will survive to breed elsewhere; nonbreeders might prefer to associate with breeders that are relatives because of the potential to accrue indirect genetic benefits by enhancing anemone and, consequently, breeder fitness. Given the potential benefits of associating with relatives, we use microsatellite loci to investigate whether or not individuals within groups of A. percula are related. We develop seven polymorphic microsatellite loci, with a number of alleles (range 2-24) and an observed level of heterozygosity (mean = 0.5936) sufficient to assess fine-scale genetic structure. The mean coefficient of relatedness among group members is 0.00 +/- 0.10 (n = 9 groups), and there are no surprising patterns in the distribution of pairwise relatedness. We conclude that A. percula live in groups of unrelated individuals. This study lays the foundation for further investigations of behavioural, population and community ecology of anemonefishes which are emerging as model systems for evolutionary ecology in the marine environment. PMID- 17845440 TI - Explicit experimental evidence for the effectiveness of proximity as mate guarding behaviour in reducing extra-pair fertilization in the Seychelles warbler. AB - Extra-pair copulations (EPCs; copulations outside the pair bond) are widespread in birds and may result in extra-pair fertilizations (EPFs). To increase reproductive success, males should not only seek to gain EPFs, but also prevent their own females from gaining EPFs. Although males could reduce the number of EPCs by their mates, this does not necessarily mean that they reduce the number of EPFs; indeed several studies have found no association between EPCs and EPFs. Male Seychelles warblers (Acrocephalus sechellensis) follow their partner closely during the period when the pair female is most receptive (fertile period). We show that males that guarded their mates more closely were less likely to have extra-pair young in their nest. This study on the Seychelles warbler is the first to provide explicit experimental evidence that mate guarding is effective in reducing EPFs. First, in territories where free-living males were induced to stop mate guarding during the pair female's fertile period, extra-pair parentage was higher than in the control group. Second, in the experimental group, the probability of having an extra-pair nestling in the nest was positively associated with the number of days during the fertile period for which mate guarding was artificially stopped. Thus, male mate guarding was effective in reducing the risk of cuckoldry. PMID- 17845441 TI - Genetic evidence supports song learning in the three-wattled bellbird Procnias tricarunculata (Cotingidae). AB - Vocal learning is thought to have evolved in three clades of birds (parrots, hummingbirds, and oscine passerines), and three clades of mammals (whales, bats, and primates). Behavioural data indicate that, unlike other suboscine passerines, the three-wattled bellbird Procnias tricarunculata (Cotingidae) is capable of vocal learning. Procnias tricarunculata shows conspicuous vocal ontogeny, striking geographical variation in song, and rapid temporal change in song within a population. Deprivation studies of vocal development in P. tricarunculata are impractical. Here, we report evidence from mitochondrial DNA sequences and nuclear microsatellite loci that genetic variation within and among the four allopatric breeding populations of P. tricarunculata is not congruent with variation in vocal behaviour. Sequences of the mitochondrial DNA control region document extensive haplotype sharing among localities and song types, and no phylogenetic resolution of geographical populations or behavioural groups. The vocally differentiated, allopatric breeding populations of P. tricarunculata are only weakly genetically differentiated populations, and are not distinct taxa. Mitochondrial DNA and microsatellite variation show small (2.9% and 13.5%, respectively) but significant correlation with geographical distance, but no significant residual variation by song type. Estimates of the strength of selection that would be needed to maintain the observed geographical pattern in vocal differentiation if songs were genetically based are unreasonably high, further discrediting the hypothesis of a genetic origin of vocal variation. These data support a fourth, phylogenetically independent origin of avian vocal learning in Procnias. Geographical variations in P. tricarunculata vocal behaviour are likely culturally evolved dialects. PMID- 17845442 TI - High frequency of multiple paternity in the largest rookery of Mediterranean loggerhead sea turtles. AB - Mating systems are a central component in the evolution of animal life histories and in conservation genetics. The patterns of male reproductive skew and of paternal shares in batches of offspring, for example, affect genetic effective population size. A prominent characteristic of mating systems of sea turtles seem to be a considerable intra- and interspecific variability in the degree of polyandry. Because of the difficulty of observing the mating behaviour of sea turtles directly in the open sea, genetic paternity analysis is particularly useful for gaining insights into this aspect of their reproductive behaviour. We investigated patterns of multiple paternity in clutches of loggerhead sea turtles in the largest Mediterranean rookery using four highly variable microsatellite loci. Furthermore, we tested for a relationship between the number of fathers detected in clutches and body size of females. More than one father was detected in the clutches of 14 out of 15 females, with two clutches revealing the contribution of at least five males. In more than half the cases, the contributions of different fathers to a clutch did not depart from equality. The number of detected fathers significantly increased with increasing female body size. This relationship indicates that males may prefer to mate with large, and therefore productive, females. Our results suggest that polyandry is likely to increase effective population size compared to a population in which females would mate with only one male; male reproductive contributions being equal. PMID- 17845443 TI - Risk of ectoparasitism and genetic diversity in a wild lesser kestrel population. AB - Parasites and infectious diseases are major determinants of population dynamics and adaptive processes, imposing fitness costs to their hosts and promoting genetic variation in natural populations. In the present study, we evaluate the role of individual genetic diversity on risk of parasitism by feather lice Degeeriella rufa in a wild lesser kestrel population (Falco naumanni). Genetic diversity at 11 microsatellite loci was associated with risk of parasitism by feather lice, with more heterozygous individuals being less likely to be parasitized, and this effect was statistically independent of other nongenetic parameters (colony size, sex, location, and year) which were also associated with lice prevalence. This relationship was nonlinear, with low and consistent prevalences among individuals showing high levels of genetic diversity that increased markedly at low levels of individual heterozygosity. This result appeared to reflect a genome-wide effect, with no single locus contributing disproportionably to the observed effect. Thus, overall genetic variation, rather than linkage of markers to genes experiencing single-locus heterosis, seems to be the underlying mechanism determining the association between risk of parasitism and individual genetic diversity in the study host-parasite system. However, feather lice burden was not affected by individual heterozygosity; what suggest that differences in susceptibility, rather than variation in defences once the parasite has been established, may shape the observed pattern. Overall, our results highlight the role of individual genetic diversity on risk of parasitism in wild populations, what has both important evolutionary implications and major consequences for conservation research on the light of emerging infectious diseases that may endanger genetically depauperated populations. PMID- 17845444 TI - Niche partitioning of closely related symbiotic dinoflagellates. AB - Reef-building corals are fundamental to the most diverse marine ecosystems, yet a detailed understanding of the processes involved in the establishment, persistence and ecology of the coral-dinoflagellate association remains largely unknown. This study explores symbiont diversity in relation to habitat by employing a broad-scale sampling regime using ITS2 and denaturing gradient gel electrophoresis. Samples from Pocillopora damicornis, Stylophora pistillata and Seriatopora hystrix all harboured host-specific clade C symbiont types at Heron Island (Great Barrier Reef, Australia). While Ser. hystrix associated with a single symbiont profile along its entire depth distribution, both P. damicornis and Sty. pistillata associated with multiple symbiont profiles that showed a strong zonation with depth. It is shown that, with an increased sampling effort, previously identified 'rare' symbiont types within this group of host species are in fact environmental specialists. A multivariate approach was used to expand on the common distinction of symbionts by a single genetic identity. It shows merit in its capacity not only to include all the variability present within the marker region but also to reliably represent ecological diversification of symbionts. Furthermore, the cohesive species concept is explored to explain how niche partitioning may drive diversification of closely related symbiont lineages. This study provides thus evidence that closely related symbionts are ecologically distinct and fulfil their own niche within the ecosystem provided by the host and external environment. PMID- 17845446 TI - Imagining a new world: using internationalism to overcome the 10/90 gap in bioethics. AB - The IAB Presidential Address was delivered by Alexander Capron to the internationally gathered audience at the Closing Ceremony of the 8th World Congress of Bioethics, Beijing on 9th August 2006. PMID- 17845447 TI - Playing God and the ethics of divine names: an Islamic paradigm for biomedical ethics. AB - The notion of 'playing God' frequently comes to fore in discussions of bioethics, especially in religious contexts. The phrase has always been analyzed and discussed from Christian and secular standpoints. Two interpretations exist in the literature. The first one takes 'God' seriously and playing 'playfully'. It argues that this concept does state a principle but invokes a perspective on the world. The second takes both terms playfully. In the Islamic Intellectual tradition, the Sufi concept of 'adopting divine character traits' provides a legitimate paradigm for 'playing God'. This paradigm is interesting because here we take both terms 'God' and 'playing' seriously. It is significant for the development of biomedical ethics in contemporary Islamic societies as it can open new vistas for viewing biotechnological developments. PMID- 17845449 TI - Threshold considerations in fair allocation of health resources: justice beyond scarcity. AB - Application of egalitarian and prioritarian accounts of health resource allocation in low-income countries have both been criticized for implying distribution outcomes that allow decreasing/undermining health gains and for tolerating unacceptable standards of health care and health status that result from such allocation schemes. Insufficient health care and severe deprivation of health resources are difficult to accept even when justified by aggregative efficiency or legitimized by fair deliberative process in pursuing equality and priority oriented outcomes. I affirm the sufficientarian argument that, given extreme scarcity of public health resources in low-income countries, neither health status equality between populations nor priority for the worse off is normatively adequate. Nevertheless, the threshold norm alone need not be the sole consideration when a country's total health budget is extremely scarce. Threshold considerations are necessary in developing a theory of fair distribution of health resources that is sensitive to the lexically prior norm of sufficiency. Based on the intuition that shares must not be taken away from those who barely achieve a minimal level of health, I argue that assessments based on standards of minimal physical/mental health must be developed to evaluate the sufficiency of the total resources of health systems in low-income countries prior to pursuing equality, priority, and efficiency based resource allocation. I also begin to examine how threshold sensitive health resource assessment could be used in the Philippines. PMID- 17845448 TI - Transhumanism and moral equality. AB - Conservative thinkers such as Francis Fukuyama have produced a battery of objections to the transhumanist project of fundamentally enhancing human capacities. This article examines one of these objections, namely that by allowing some to greatly extend their capacities, we will undermine the fundamental moral equality of human beings. I argue that this objection is groundless: once we understand the basis for human equality, it is clear that anyone who now has sufficient capacities to count as a person from the moral point of view will continue to count as one even if others are fundamentally enhanced; and it is mistaken to think that a creature which had even far greater capacities than an unenhanced human being should count as more than an equal from the moral point of view. PMID- 17845450 TI - Frozen embryos, genetic information and reproductive rights. AB - Recent ethical and legal challenges have arisen concerning the rights of individuals over their IVF embryos, leading to questions about how, when the wishes of parents regarding their embryos conflict, such situations ought to be resolved. A notion commonly invoked in relation to frozen embryo disputes is that of reproductive rights: a right to have (or not to have) children. This has sometimes been interpreted to mean a right to have, or not to have, one's own genetic children. But can such rights legitimately be asserted to give rise to claims over embryos? We examine the question of property in genetic material as applied to gametes and embryos, and whether rights over genetic information extend to grant control over IVF embryos. In particular we consider the purported right not to have one's own genetically related children from a property-based perspective. We argue that even if we concede that such (property) rights do exist, those rights become limited in scope and application upon engaging in reproduction. We want to show that once an IVF embryo is created for the purpose of reproduction, any right not to have genetically-related children that may be based in property rights over genetic information is ceded. There is thus no right to prevent one's IVF embryos from being brought to birth on the basis of a right to avoid having one's own genetic children. Although there may be reproductive rights over gametes and embryos, these are not grounded in genetic information. PMID- 17845451 TI - Moral status of embryonic stem cells: perspective of an African villager. AB - One of the most important as well as most awesome achievements of modern biotechnology is the possibility of cloning human embryonic stem cells, if not human beings themselves. The possible revolutionary role of such stem cells in curative, preventive and enhancement medicine has been voiced and chorused around the globe. However, the question of the moral status of embryonic stem cells has not been clearly and unequivocally answered. Taking inspiration from the African adage that 'the hand that reaches beneath the incubating hen is not guiltless', I attempt answering this question, from the background of traditional African moral sensibility and sensitivity. I reach the following conclusions. Stem cells in themselves do not have human status and therefore lack moral worth/value. Embryos do have human status and a morally significant line cannot be drawn between human embryos and other human beings. What is morally at stake in stem cell research is therefore the question of the source of derivation or generation of the cells, not of the cells as such. PMID- 17845452 TI - Postmenopausal motherhood: immoral, illegal? A case study. AB - The paper explores the ethics of post-menopausal motherhood by looking at the case of Adriana Iliescu, the oldest woman ever to have given birth (so far). To this end, I will approach the three most common objections brought against the mother and/or against the team of healthcare professionals who made it happen: the age of the mother, the fact that she is single, the appropriateness of her motivation and of that of the medical team. PMID- 17845454 TI - Is global ethics moral neo-colonialism? An investigation of the issue in the context of bioethics. AB - This paper considers the possibility and desirability of global ethics in light of the claim that 'global ethics' in any form is not global, but simply the imposition of one form of local ethics--Western ethics--and, as such, a form of moral neo-colonialism. The claim that any form of global ethics is moral neo colonialism is outlined using the work of a group of 'developing world bioethicists' who are sceptical of the possibility of global ethics. The work of virtue ethicists is then introduced and compared to the position of the developing world bioethicists in order to show that the divide between 'Western' and 'non-Western' ethics is exaggerated. The final section of the paper turns to the practical arena and considers the question of global ethics in light of practical issues in bioethics. The paper concludes that practical necessity is driving the creation of global ethics and thus the pertinent question is no longer 'Whether global ethics?', but 'Why global ethics?'. PMID- 17845455 TI - A critique of the innovation argument against a national health program. AB - President Bush and his Council of Economic Advisors have claimed that the US shouldn't adopt a national health program because doing so would slow innovation in health care. Some have attacked this argument by challenging its moral claim that innovativeness is a good ground for choosing between health care systems. This reply is misguided. If we want to refute the argument from innovation, we have to undercut the premise that seems least controversial--the premise that our current system produces more innovation than a national health program would. I argue that this premise is false. The argument requires clarifying the concept 'national health program' and examining various theories of human well-being. PMID- 17845456 TI - Boonin on the future-like-ours argument against abortion. AB - I argue that David Boonin has failed in his attempt to undermine Donald Marquis's future-like-ours argument against abortion. I show that the ethical principle advanced by Boonin in his critique to that argument is unable, contrary to what he claims, to account for the wrongness of infanticide. Then I argue that Boonin's critique misrepresents Marquis's argument. Although there is a way to restate his critique in order to avoid the misrepresentation, the success of such restatement is precluded by the wrongness of infanticide. PMID- 17845457 TI - The pro-life argument from substantial identity and the pro-choice argument from asymmetric value: a reply to Patrick Lee. AB - Lee claims that foetuses and adult humans are phases of the same identical substance, and thus have the same moral status because: first, foetuses and adults are the same physical organism, and second, the development from foetus to adult is quantitative and thus not a change of substance. Versus the first argument, I contend that the fact that foetuses and adults are the same physical organism implies only that they are the same thing but not the same substance, much as living adults and their corpses are the same thing (same body) but not the same substance. Against Lee's second argument, I contend that Lee confuses the nature of a process with the nature of its result. A process of quantitative change can produce a change in substance. Lee also fails to show that foetuses are rational and thus have all the essential properties of adults, as required for them to be the same substance. Against the pro-choice argument from asymmetric value (that only the fact that a human has become conscious of its life and begun to count on its continuing can explain human life's asymmetric moral value, i.e. that it is vastly worse to kill a human than not to produce one), Lee claims that foetus's lives are asymmetrically valuable to them before consciousness. This leads to counterintuitive outcomes, and it confuses the goodness of life (a symmetric value that cannot account for why it is worse to kill a human than not produce one) with asymmetric value. PMID- 17845458 TI - Solidarity and justice as guiding principles in genomic research. AB - In genomic research the ideal standard of free, informed, prior and explicit consent is sometimes difficult to apply. This has raised concern that important genomic research will be restricted. Different consent procedures have therefore been proposed. This paper explicitly examines the question how, in genomic research, the principles of solidarity and justice can be used to justify forms of diminished individual control over personal data and bio-samples. After a discussion of the notions of solidarity and justice and how they can be related to health care and genomic research, we examine how and in which situations these notions can form a strong moral basis for demanding certain financial sacrifices. Then we examine when these principles can justify consent procedures which diverge from the ideal standard. Because much genomic research is not expected to lead to immediate (clinical) benefits we also discuss the question of whether we can be obliged to make any sacrifices for future (not yet existing) patients. We conclude with the formulation of a number of conditions that have to be met before autonomy sacrifices can be reasonably demanded in genomic research. PMID- 17845461 TI - Survival lotteries reconsidered. AB - In 1975 John Harris envisaged a survival lottery to redistribute organs from one to a greater number in order to reduce number of deaths as a consequence of organ failure. In this paper I reach a conclusion about when running a survival lottery is permissible by looking at the reason prospective participants have for allowing the procedure from a contractual perspective. I identify three versions of the survival lottery. In a National Lottery, everyone within a jurisdiction is a candidate for being a donor for everyone else, disregarding all differences between individuals' eventual possibility of needing an organ. In a Group Specific Lottery, it is a question of running a lottery among members of a specific group who share the same probability of getting organ failure. In a Local Lottery one randomises among individuals who are already in need of a new organ but who happen to be compatible and in need of different organs. While the first is vulnerable to considerations of fairness, it is difficult to perceive a feasible way to implement the second option that does not come with a host of unwelcome consequences. I argue, however, that it is permissible to run Local Lotteries. PMID- 17845462 TI - Management of natural and bioterrorism induced pandemics. AB - A recent approach for bioterrorism risk management calls for stricter regulations over biotechnology as a way to control subversion of technology that may be used to create a man-made pandemic. This approach is largely unworkable given the increasing pervasiveness of molecular techniques and tools throughout society. Emerging technology has provided the tools to design much deadlier pathogens but concomitantly the ability to respond to emerging pandemics to reduce mortality has also improved significantly in recent decades. In its historical context determining just how 'risky' biological weapons is an important consideration for decision making and resource allocation. Management should attempt to increase capacity, share resources, provide accurate infectious disease reporting, deliver information transparency and improve communications to help mitigate the magnitude of future pandemics. PMID- 17845463 TI - Uses of respect and uses of the human embryo. AB - In most parts of the world, research on the human embryo is subject to tight controls. In the United Kingdom it is restricted by means of both a fourteen-day time limit and the permitted purposes of the research. One of the ways in which the argument for these restrictions has been put is in terms of respect. That is, the human embryo is said to be the kind of thing that is worthy of a measure of respect such that there are limits to what can be done to it. This paper considers some of the ways in which this principle of respect has been understood as well as some objections to the very idea that research resulting in the destruction of the human embryo can claim to show that embryo respect. It will be argued that an account of 'respectful destruction' can be articulated on the grounds of our shared finitude as human moral agents, and in particular on the grounds of our shared lack of certainty regarding the moral status of the embryo. PMID- 17845464 TI - Potentiality and human embryos. AB - Consideration of the potentiality of human embryos to develop characteristics of personhood, such as intellect and will, has figured prominently in arguments against abortion and the use of human embryos for research. In particular, such consideration was the basis for the call of the US President's Council on Bioethics for a moratorium on stem cell research on human embryos. In this paper, I critique the concept of potentiality invoked by the Council and offer an alternative account. In contrast to the Council's view that an embryo's potentiality is determined by definition and is not affected by external conditions that may prevent certain possibilities from ever being realized, I propose an empirically grounded account of potentiality that involves an assessment of the physical and decisional conditions that may restrict an embryo's possibilities. In my view, some human embryos lack the potentiality to become a person that other human embryos have. Assuming for the sake of argument that the potential to become a person gives a being special moral status, it follows that some human embryos lack this status. This argument is then used to support Gene Outka's suggestion that it is morally permissible to experiment on 'spare' frozen embryos that are destined to be destroyed. PMID- 17845465 TI - The development and nature of the ordinary/extraordinary means distinction in the Roman Catholic tradition. AB - In the Roman Catholic tradition the nature of the ordinary/extraordinary means distinction is best understood in light of its historical development. The moralist tradition that reared and nurtured this distinction implicitly developed a set of general criteria to distinguish the extraordinary from the ordinary. These criteria, conjoined with the context within which they were understood, can play an important role in refereeing the contemporary debate over the aggressiveness of medical treatment and the extent of one's moral obligation. PMID- 17845466 TI - Ethical aspects of limiting residents' work hours. AB - DEFINITION OF THE PROBLEM: The regulation of residents' work hours involves several ethical conflicts which need to be systematically analysed and evaluated. ARGUMENTS AND CONCLUSION: The most important ethical principle when regulating work hours is to avoid the harm resulting from the over-work of physicians and from an excessive division of labour. Additionally, other ethical principles have to be taken into account, in particular the principles of nonmaleficence and beneficence for future patients and for physicians. The article presents arguments for balancing the relevant ethical principles and analyses the structural difficulties that occur unavoidably in any regulation of the complex activities of physicians. PMID- 17845469 TI - Responsibility for control; ethics of patient preparation for self-management of chronic disease. AB - Patient self-management (SM) of chronic disease is an evolving movement, with some forms documented as yielding important outcomes. Potential benefits from proper preparation and maintenance of patient SM skills include quality care tailored to the patient's preferences and life goals, and increase in skills in problem solving, confidence and success, generalizable to other parts of the patient's life. Four central ethical issues can be identified. 1) insufficient patient/family access to preparation that will optimize their competence to SM without harm to themselves, 2) lack of acknowledgement that an ethos of patient empowerment can mask transfer of responsibility beyond patient/family competency to handle that responsibility, 3) prevailing assumptions that preparation for SM cannot result in harm and that its main purpose is to deliver physician instructions, and 4) lack of standards for patient selection, which has the potential to exclude individuals who could benefit from learning to SM. Technology assessment offers one framework through which to examine available data about efficacy of patient SM and to answer the central question of what conditions must be put in place to optimize the benefits of SM while assuring that potential harms are controlled. PMID- 17845470 TI - Acculturation and end-of-life decision making: comparison of Japanese and Japanese-American focus groups. AB - Variation in decision-making about end-of-life care among ethnic groups creates clinical conflicts. In order to understand changes in preferences for end-of-life care among Japanese who immigrate to the United States, we conducted 18 focus groups with 122 participants: 65 English-speaking Japanese Americans, 29 Japanese speaking Japanese Americans and 28 Japanese living in Japan. Negative feelings toward living in adverse health states and receiving life-sustaining treatment in such states permeated all three groups. Fear of being meiwaku, a physical, psychological or financial caregiving burden on loved ones, was a prominent concern. They preferred to die pokkuri (popping off) before they become end stage or physically frail. All groups preferred group-oriented decision-making with family. Although advance directives were generally accepted, Japanese participants saw written directives as intrusive whereas Japanese Americans viewed them mainly as tools to reduce conflict created by dying person's wishes and a family's kazoku no jo--responsibility to sustain the dying patient. These findings suggest that in the United States Japanese cultural values concerning end-of-life care and decision-making process are largely preserved. PMID- 17845471 TI - What motivates women to take part in clinical and basic science endometriosis research? AB - BACKGROUND: The objective of this study was to identify factors motivating women to take part in endometriosis research and to determine if these factors differ for women participating in clinical versus basic science studies. METHODS: A consecutive series of 24 women volunteering for participation in endometriosis related research were asked to indicate, in their own words, why they chose to volunteer. In addition, the women were asked to rate, on a scale of 0 to 10, sixteen potentially motivating factors. The information was gathered in the form of an anonymous self-administered questionnaire. RESULTS: Strong motivating factors (mean score > 8) included potential benefit to other women's health, improvement to one's own condition, and participation in scientific advancement. Weak motivating factors (mean score < 3) included financial compensation, making one's doctor happy, and use of 'natural' products. No difference was detected between clinical and basic science study participants. CONCLUSION: This study is the first study to specifically investigate the factors that motivate women to take part in endometriosis research. Understanding why women choose to take part in such research is important to the integrity of the informed consent process. The factors most strongly motivating women to participate in endometriosis research related to improving personal or public health; the weakest, to financial compensation and pleasing the doctor. PMID- 17845472 TI - Why Eberl is wrong. Reflections on the beginning of personhood. AB - In a paper published in Bioethics, Jason Eberl has argued that early embryos are not persons and should not be granted the status possessed by them. Eberl bases this position upon the following claims: (1) The early embryo has a passive potentiality for development into a person. (2) The early embryo has not established both 'unique genetic identity' and 'ongoing ontological identity', which are necessary conditions for ensoulment. (3) The early embryo has a low probability of developing into a more developed embryo. This paper examines these claims. I argue against (1) that a plausible view is that the early embryo has an active potentiality to grow into a more developed embryo. Against (2), I argue that neither 'unique genetic identity' nor 'ongoing ontological identity' are necessary conditions for ensoulment, and that 'ongoing ontological identity' is established between early embryos and more developed embryos. Against (3), I argue that the fact that the early embryo has a low probability of developing into a more developed embryo, if true, does not warrant the conclusion that the early embryo is not a person. If Eberl is right that the human soul is that which organises the activities of a human being and that ensouled humans are persons, embryos are persons from conception. PMID- 17845474 TI - Regulation of clinical research and bioethics in Portugal. AB - This article presents an overview of the Portuguese transposition of the European Directive on Good Clinical Practice (2001/20/E) concerning scientific and academic debates on bioethics and clinical investigation. Since the Directive was transposed into Portuguese law by its National Assembly, the bureaucracy of clinical trials has been ever more complex. Despite demands for swift application processes by the Pharmaceutical industry, supported by the European Parliament, the Directive's transcription to the national law has not always delivered the expected outcome. However, this has led to an increased number of applications for clinical trials in Portuguese hospitals. In this article I revise bioethical publications and decree-laws enabling an informed appraisal of the anxieties and prospects for the implementation of the clinical trials Directive in Portugal. This article also places the European Directive in the field of sociology of bioethics, arguing that Portuguese bioethical institutions differ from those of the US, and also from Northern European counterparts. The main divergence is that those people in Portugal who claim expertise in 'legal' bioethics do not dominate either the bureaucratic structure of research or ethics committees for health. Even experts in the applied ethics field now claim that 'professional bioethicists do not exist'. The recent creation of a national Ethics Committee for Clinical Investigation (CEIC) in line with the European Directive on Good Clinical Practice (GCP) will not change the present imbalance between different professional jurisdictions in the national bioethical debate in Portugal. PMID- 17845476 TI - Parental virtue: a new way of thinking about the morality of reproductive actions. AB - In this paper I explore the potential of virtue ethical ideas to generate a new way of thinking about the ethical questions surrounding the creation of children. Applying ideas from neo-Aristotelian virtue ethics to the parental sphere specifically, I develop a framework for the moral assessment of reproductive actions that centres on the concept of parental virtue. I suggest that the character traits of the good parent can be used as a basis for determining the moral permissibility of a particular reproductive action. I posit three parental virtues and argue that we can see the moral status of a reproductive action as determined by the relationship between such an action and (at least) these virtues. Using a case involving selection for deafness, I argue that thinking in terms of the question 'would a virtuous parent do this?' when morally assessing reproductive action is a viable and useful way of thinking about issues in reproductive ethics. PMID- 17845477 TI - The parental obligation to expand a child's range of open futures when making genetic trait selections for their child. AB - As parents become increasingly able to make genetic trait selections on behalf of their children, they will need ethical guidance in deciding what genetic traits to select. Dena Davis has argued that parents act unethically if they make selections that constrain their child's range of futures. But some selections may expand the child's range of futures. And other selections may shift the child's range of futures, without either constraining or expanding that range. I contend that not only would parents act unethically if they make selections that constrain the range of their child's futures, they would act unethically if they make selections that shift the range of their child's futures, because selections that shift the range of the child's futures would allow parents to over-determine their child's futures. Thus, I contend that parents would act ethically only if they make selections that expand their child's range of futures. PMID- 17845478 TI - Embryonic potential and stem cells. AB - This paper examines three arguments that use the concept of potential to identify embryos that are morally suitable for embryonic stem cell research (ESCR). According to the first argument, due to Ronald Green, the fact that they are scheduled for disposal makes embryos left over from IVF treatments morally appropriate for research. Paul McHugh argues that embryos created by somatic cell nuclear transfer differ from those that result directly from the meeting of sperm and egg in having potential especially conducive to the therapeutic use of their stem cells. I reject both of these arguments. According to the way of making distinctions in embryonic potential that I defend, it is the absence of a functional relationship with a womb that marks embryos morally suitable for ESCR. PMID- 17845479 TI - 'You don't make genetic test decisions from one day to the next'--using time to preserve moral space. AB - The part played by time in ethics is often taken for granted, yet time is essential to moral decision making. This paper looks at time in ethical decisions about having a genetic test. We use a patient-centred approach, combining empirical research methods with normative ethical analysis to investigate the patients' experience of time in (i) prenatal testing of a foetus for a genetic condition, (ii) predictive or diagnostic testing for breast and colon cancer, or (iii) testing for Huntington's disease (HD). We found that participants often manipulated their experience of time, either using a stepwise process of microdecisions to extend it or, under the time pressure of pregnancy, changing their temporal 'depth of field'. We discuss the implications of these strategies for normative concepts of moral agency, and for clinical ethics. PMID- 17845480 TI - Ethics and drug resistance. AB - This paper reviews the dynamics behind, and ethical issues associated with, the phenomenon of drug resistance. Drug resistance is an important ethical issue partly because of the severe consequences likely to result from the increase in drug resistant pathogens if more is not done to control them. Drug resistance is also an ethical issue because, rather than being a mere quirk of nature, the problem is largely a product of drug distribution. Drug resistance results from the over-consumption of antibiotics by the wealthy; and it, ironically, results from the under-consumption of antibiotics, usually by the poor or otherwise marginalized. In both kinds of cases the phenomenon of drug resistance illustrates why health (care)--at least in the context of infectious disease- should be treated as a (global) public good. The point is that drug resistance involves 'externalities' affecting third parties. When one patient develops a resistant strain of disease because of her over- or under-consumption of medication, this more dangerous malady poses increased risk to others. The propriety of free-market distribution of goods subject to externalities is famously dubious--given that the 'efficiency' rationale behind markets assumes an absence of externalities. Market failure in the context of drug resistance is partly revealed by the fact that no new classes of antibiotics have been developed since 1970. I conclude by arguing that the case of drug resistance reveals additional reasons--to those traditionally appealed to by bioethicists- for treating health care as something special when making policy decisions about its distribution. PMID- 17845481 TI - Health, justice, and the environment. AB - In this article, we argue that the scope of bioethical debate concerning justice in health should expand beyond the topic of access to health care and cover such issues as occupational hazards, safe housing, air pollution, water quality, food and drug safety, pest control, public health, childhood nutrition, disaster preparedness, literacy, and many other environmental factors that can cause differences in health. Since society does not have sufficient resources to address all of these environmental factors at one time, it is important to set priorities for bioethical theorizing and policy formation. Two considerations should be used to set these priorities: (1) the impact of the environmental factor on health inequality, and (2) the practicality of addressing the factor. PMID- 17845483 TI - 'Setting a principled boundary'? Euthanasia as a response to 'life fatigue'. AB - The Dutch case of Brongersma presents novel challenges to the definition and evaluation of voluntary euthanasia since it involved a doctor assisting the suicide of an individual who was (merely?) 'tired of life'. Legal officials had called on the courts to 'set a principled boundary', excluding such cases from the scope of permissible voluntary euthanasia, but they arguably failed. This failure is explicable, however, since the case seems justifiable by reference to the two major principles in favour of that practice, respect for autonomy and beneficence. Ultimately, it will be argued that those proponents of voluntary euthanasia who are wary of its use in such circumstances may need to draw upon 'practical' objections, in order to erect an otherwise arbitrary perimeter. Furthermore, it will be suggested that the issues raised by the case are not peculiarly Dutch in nature and that, therefore, there are lessons here for other jurisdictions too. PMID- 17845484 TI - Physician assisted suicide: a new look at the arguments. AB - In this paper, I examine the argumens agains physician assisted suicide (PAS). Many of these arguments are consequentialist. Consequentialist arguments rely on empirical claims about the future and thus their strength depends on how likely it is that the predictions will be realized. I discuss these predictions against the backdrop of Oregon's Death with Dignity Act and the practice of PAS in the Netherlands. I then turn to a specific consequentialist argument against PAS - Susan M. Wolfs feminist critique of the practice. Finally, I examine the two most prominent deontological arguments against PAS. Ultimately, I conclude that no anti-PAS argument has merit. Although I do not provide positive arguments for PAS, if none of the arguments against it are strong, we have no reason not to legalize it. PMID- 17845485 TI - Execution by lethal injection, euthanasia, organ-donation and the proper goals of medicine. AB - In a recent issue of this journal, David Silver and Gerald Dworkin discuss the physicians' role in execution by lethal injection. Dworkin concludes that discussion by stating that, at that point, he is unable to think of an acceptable set of moral principles to support the view that it is illegitimate for physicians to participate in execution by lethal injection that would not rule out certain other plausible moral judgements, namely that euthanasia is under certain conditions legitimate and that organ-donation surgery is sometimes permissible. This article draws attention to some problems in the views of Silver and Dworkin and suggests moral principles which support the three moral views just mentioned. PMID- 17845486 TI - Benefiting from past wrongdoing, human embryonic stem cell lines, and the fragility of the German legal position. AB - This paper examines the logic and morality of the German Stem Cell Act of 2002. After a brief description of the law's scope and intent, its ethical dimensions are analysed in terms of symbolic threats, indirect consequences, and the encouragement of immorality. The conclusions are twofold. For those who want to accept the law, the arguments for its rationality and morality can be sound. For others, the emphasis on the uniqueness of the German experience, the combination of absolute and qualified value judgments, and the lingering questions of indirect encouragement of immoral activities will probably be too much. PMID- 17845487 TI - John Harris' argument for a duty to research. AB - John Harris suggests that partcipation in or support research, particularly medical research, is a moral duty. One kind of defence of this position rests on an appeal to the past, and produces two arguments. The first of these arguments is that it is unfair to accept the benefits of research without contributing something back in the form of support for, or participation in, research. A second argument is that we have a social duty to maintain those practices and institutions that sustain us, such as those which contribute to medical knowledge. This argument is related to the first, but it does not rely so heavily on fairness. Another kind of defence of the duty to research rests on an appeal to the future benefits of research: research is an effective way to discharge a duty to rescue others from serious illness or death, therefore we have a duty to research. I suggest that all three of Harris' lines fail to provide a compelling duty to research and spell out why. Moreover, not only do the lines of argument fail in their own terms: in combination, they turn out to be antagonistic to the very position that Harris wants to defend. While it is not my intention here to deny that there might be a duty to research, I claim that Harris' argument for the existence of such a duty is not the best way to establish it. PMID- 17845488 TI - Islamic medical ethics: a primer. AB - Modern medical practice is becoming increasingly pluralistic and diverse. Hence, cultural competency and awareness are given more focus in physician training seminars and within medical school curricula. A renewed interest in describing the varied ethical constructs of specific populations has taken place within medical literature. This paper aims to provide an overview of Islamic Medical Ethics. Beginning with a definition of Islamic Medical Ethics, the reader will be introduced to the scope of Islamic Medical Ethics literature, from that aimed at developing moral character to writings grounded in Islamic law. In the latter form, there is an attempt to derive an Islamic perspective on bioethical issues such as abortion, gender relations within the patient-doctor relationship, end-of life care and euthanasia. It is hoped that the insights gained will aid both clinicians and ethicists to better understand the Islamic paradigm of medical ethics and thereby positively affect patient care. PMID- 17845490 TI - Racist organ donors and saving lives. AB - This paper considers what should be done about offers of organs for transplant that come with racist strings attached. Saving lives or improving their quality seem powerful reasons to accept the offer. Fairness, justice, and rejecting racism seem like powerful reasons against. This paper argues that conditional allocation should occur when it would provide access to organs for at least one person without costing others their access to organs. The bulk of the paper concentrates on defending this claim against these objections: (i) that the good that might come about through conditional allocation does so through wrongful complicity in the racist's wrongdoing; (ii) that conditional allocation symbolizes support for racism; and (iii) that conditional allocation is unjust or unfair and is, for that reason, impermissible. The final section, on conditional allocation as a policy, considers the speculative possibility that conditional allocation would reduce access to organs for some, but it argues that, even then, conditional allocation could be justified. PMID- 17845491 TI - Illness, suffering and voluntary euthanasia. AB - It is often accepted that we may legitimately speak about voluntary euthanasia only in cases of persons who are suffering because they are incurably injured or have an incurable disease. This article argues that when we consider the moral acceptability of voluntary euthanasia, we have no good reason to concentrate only on persons who are ill or injured and suffering. PMID- 17845492 TI - Pascal's Wager and the persistent vegetative state. AB - I've argued that a version of Pascal's Wager applies to PVS so forcefully that no one who declines continued life without considering it makes a reasoned and informed decision. Thomas Mappes objects that my argument is much more limited than I realize. Of special interest is his appeal to an emerging diagnostic category, the 'minimally conscious state; to argue that there is much to lose in gambling on life. I will defend the Wager. Along the way I maintain that the chance of recovery from long-term PVS is much better than represented (as is the prospect of regaining independence if one recovers consciousness), and that the 1994 Multi-Society Task Force definitions of 'permanent' PVS are confused in ways that make crafting advance directives dangerously difficult. Valid advance directives require informed consent, I argue; the Wager needs to be part of the process. A consequence of my argument is that withdrawing medically-delivered nutrition and hydration from PVS patients is much harder to justify. PMID- 17845493 TI - Substantial identity and the right to life: a rejoinder to Dean Stretton. AB - In this article, I reply to criticisms of Dean Stretton of the pro-life argument from substantial identity. When the criterion for the right to life proposed by most proponents of the pro-life position is rightly understood--being a person, a distinct substance of a rational nature--this position does not lead to the difficulties Stretton claims it does. PMID- 17845494 TI - An ironic reductio for a 'pro-life' argument: Hurlbut's proposal for stem cell research. AB - William Hurlbut, a Stanford University bioethicist and member of the President's Council on Bioethics, recently proposed a solution to the current impasse over human embryonic stem cell research in the United States. He suggested that researchers could use genetic engineering and somatic cell nuclear transfer (i.e. cloning) to develop human 'pseudo-embryos' that have no potential to develop fully into human persons. According to Hurlbut, even thinkers who typically ascribe high moral status to human embryos could approve of destroying these 'pseudo-embryos' for the sake of harvesting human embryonic stem cells. This essay argues, first, that an argument based on the 'paradox of the heap' (an argument that many 'pro-life' thinkers employ in order to defend the notion that human embryos have high moral value from the moment of conception) challenges the ethical legitimacy of Hurlbut's proposal. Second, the paper argues that this conflict may illustrate a reductio ad absurdum for this 'pro-life' argument itself rather than being a problem for Hurlbut's proposal. As a result, the paper challenges the 'pro-life'strategy of arguing that one should respond to uncertainty about the moral status of developing embryos by being morally 'cautious' and granting all human embryos full moral status from the moment of conception. It appears that one is faced with a complex series of choices (about where to draw the moral line between entities that are human persons and entities that are not), and a strict moral 'cautiousness' about this series of choices may ultimately lead to absurdity. PMID- 17845495 TI - Commentary: Science scandal or ethics scandal? Olivieri redux. AB - Dr. Nancy Olivieri has become an icon of research integrity for her insistence on publishing adverse data about a drug she was investigating. She has been celebrated world-wide as a hero of biomedical ethics for her bravery in disclosing potential dangers to research subjects, in the face of both drug company threats and coercive pressures from her hospital and university. Like so many other 'whistle-blowers' however, she now faces both personal vilification and disturbing accusations of scientific error. The case against Olivieri is assessed and found to be baseless. PMID- 17845497 TI - What is it to be a daughter? Identities under pressure in dementia care. AB - This article concentrates on the care for people who suffer from progressive dementia. Dementia has a great impact on a person's well-being as well as on his or her social environment. Dealing with dementia raises moral issues and challenges for participants, especially for family members. One of the moral issues in the care for people with dementia is centred on responsibilities; how do people conceive and determine their responsibilities towards one another? To investigate this issue we use the theoretical perspective of Margaret Walker. She states that ideas about identity play a crucial role in patterns of normative expectations with regard to the distribution of responsibilities in daily practices of care. The results of this study show how the identity of a family member is put under pressure and changes during her loved one's illness that leads to difficulties and misunderstandings concerning the issue of responsibility These results offer an insight into the complexities of actual practices of responsibility and highlight the importance for those caring for people with dementia of attending carefully to how they see themselves and how they see other people involved (Who am I? Who do I want to be for the other?). Answers to such questions show what people expect from themselves and from one another, and how they at any rate, are distributing responsibilities in a given situation. Professional caregivers should take into account that family members might have different ideas about who they are and consequently about what their responsibilities are. PMID- 17845498 TI - Nothing but the truth? On truth and deception in dementia care. AB - Lies and deception are often used in the care for demented elderly and often with the best intentions. However, there is a strong moral presumption against all forms of lying and deceiving. The goal of this article is to examine and evaluate concrete examples of deception and lies in dementia care, while addressing some fundamental issues in the process. It is argued that because dementia slowly diminishes the capacities one needs to distinguish between truths and falsehoods, the ability to be lied to also disappears. When the moral reasons to reject lying are explored, it becomes clear that most of them also hold where demented patients are concerned, though this also depends on the capacities of the patient. Lying, though prima facie wrong, can sometimes be justified with an appeal to well-being. The relationship between well-being and the truth is further explored. Two examples of deceiving demented patients for reasons of beneficence are discussed, from which it can be concluded that although in some cases beneficent lies or deception will not enhance patients' well-being, there are circumstances in which they do. In general, methods that enhance the well being of the patient without deception or lies should be favored above options that use deceit, and methods of getting the truth across without hurting the patient should be favored above blunt honesty Finally it is important to note that not only the patient but also the nursing and medical staff can be affected by the use of lies and deception. PMID- 17845499 TI - Legitimizing the shameful: end-of-life ethics and the political economy of death. AB - This paper explores one of the most politically sensitive and intellectually neglected issues in bioethics--the interface between the history of contemporary end-of-life ethics and the economics of life and death. It suggests that contrary to general belief, economic impulses have increasingly become part of the conditions in which contemporary end-of-life ethics continues to evolve. Although this conclusion does not refute the philosophical justifications provided by the ethics for itself, it may cast new light upon its social role. PMID- 17845500 TI - Death and transplantation: let's try to get things methodologically straight. PMID- 17845501 TI - Informed consent and the misattributed paternity problem in genetic counseling. AB - When misattributed paternity is discovered in the course of genetic testing, a genetic counselor is presented with a dilemma concerning whether to reveal this information to the clients. She is committed to treating the clients equally and enabling informed decision making, but disclosing the information may carry consequences for the woman that the counselor cannot judge in advance. A frequent suggestion aimed at avoiding this problem is to include the risk of discovering nonpaternity in the informed consent process for counseling. In this paper I argue that such a move does not resolve the problem, because the conflict hinges on the interpretation of equality on which the counselor operates. Given the principles of genetic counseling, neither construal of equality yields a satisfactory solution to the conflict. In fact, I conclude that including nonpaternity in informed consent is not endorsed by either view, and we are still left with the question of what to do should nonpaternity be discovered. I suggest a compromise position concerning disclosure, involving revealing relevant genetic information but withholding nonpaternity when possible. PMID- 17845502 TI - The other side of trust in health care: prescribing drugs with the potential for abuse. AB - Defining a nonpaternalistic yet achievable form of trust in medicine in an era of simultaneous patient empowerment and institutional control has been and remains an important task of bioethics. The 'crisis of trust' in medicine has been viewed mainly as the problem of getting patients to trust their health care providers, especially physicians. However, since paradigmatic cases of trust are mutual, bioethicists must pay more attention to physician trust in patients. A physician's view of the reasonableness of trust in a particular patient is affected not just by his or her relationship with that patient, but also by what is going on institutionally, professionally, legally and politically with regard to a given treatment or intervention. Since general moral principles are insufficient in determining the moral value and reasonableness of trust in particular instances, I discuss in detail the role of trust and distrust in the specific case of treating patients with medications implicated in drug abuse. I conclude that it is important to become aware, first, of the clinical significance of physician trust and distrust in patients, and second, of the many factors which inform both of these moral attitudes. These two claims together suggest that a central, but overlooked, virtue of medical practice is reflective, context-responsive trust in patients. PMID- 17845503 TI - Pharmacological modulation of gap junction function with the novel compound rotigaptide: a promising new principle for prevention of arrhythmias. AB - Existing anti-arrhythmic therapy is hampered by lack of efficacy and unacceptable side effects. Thus, ventricular tachycardia and fibrillation remains the strongest predictor of in-hospital mortality in patients with myocardial infarction. In atrial fibrillation, rhythm control with conventional ion channel blockers provide no therapeutic benefit relative to rate control. Several lines of research indicate that impaired gap junctional cell-to-cell coupling between neighbouring cardiomyocytes is critical for the development of cardiac re-entry arrhythmias. Rotigaptide is the first drug that has been developed to prevent arrhythmias by re-establishing gap junctional intercellular communication. During conditions with acute cardiac ischaemia, rotigaptide effectively prevents induction of both ventricular and atrial tachyarrhythmia. Moreover, rotigaptide effectively prevents ischaemia reperfusion arrhythmias. At the cellular level, rotigaptide inhibits ischaemia-induced dephosphorylation of Ser297 and Ser368, which is considered important for the gating of connexin43 gap junction channels. No drug-related toxicity has been demonstrated at plasma concentrations 77,000 times above therapeutic concentrations. In rats and dogs, rotigaptide reduces infarct size following myocardial infarction. A series of phase I trials has been completed in which rotigaptide has been administered intravenously to ~200 healthy persons. No drug-related side effects have been demonstrated in healthy human beings. Clinical safety, tolerability and efficacy in patients with heart disease are being evaluated in ongoing clinical trials. Rotigaptide represents a pioneering pharmacological principle with a highly favourable preclinical and clinical safety profile, which makes this molecule a promising drug candidate for the prevention of cardiac arrhythmias. PMID- 17845504 TI - Toxicity profile of lisdexamfetamine dimesylate in three independent rat toxicology studies. AB - Lisdexamfetamine dimesylate (LDX) is a d-amphetamine prodrug developed for the treatment of attention-deficit/hyperactivity disorder. The toxicity profile of orally administered LDX has been evaluated in rats. In an acute study, LDX doses of 60 mg/kg and higher caused increased motor activity. At 1000 mg/kg, one rat died and another was euthanized. In a 7-day repeat-dose study, all rats dosed with LDX (14 per dose group for each sex) showed increased activity; 10 male rats and 11 female rats at 300 mg/kg/day and 3 female rats at 100 mg/kg/day were euthanized because of self-mutilation and 1 male rat at 300 mg/kg/day was found dead. In a 28-day study, only rats at 80 mg/kg showed signs of self-mutilation and thin body condition. In both the 7- and 28-day studies, LDX caused significant changes in some blood chemistry parameters (e.g. blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase) and organ weights (e.g. particularly heart, liver, brain, and spleen). Overall, no apparent treatment related histopathologic changes were observed. Toxicokinetic assessments indicated that as the dose of LDX was increased, rats were exposed to increasing levels of LDX and d-amphetamine. The extent of exposure to LDX and d-amphetamine increased after repeated-dose in the 28-day study. The findings of the repeat dose studies indicate that the toxicity profile in rats administered LDX orally is comparable to that for d-amphetamine; however, the apparent lethal dose of LDX in rats is more than five times higher than the LD(50) of orally administered d amphetamine, supporting a putative protective effect of conjugating amphetamine with lysine. PMID- 17845505 TI - Influence of tetrahydrocurcumin on hepatic and renal functional markers and protein levels in experimental type 2 diabetic rats. AB - Curcumin is the most active component of turmeric. It is believed that curcumin is a potent antioxidant and anti-inflammatory agent. Tetrahydrocurcumin is one of the major metabolites of curcumin that exhibits many of the same physiologic and pharmacological activities as curcumin and in some systems may exert greater antioxidant activity than curcumin. Oral administration of tetrahydrocurcumin at 80 mg/kg body weight to diabetic rats for 45 days resulted in a significant reduction in blood glucose and significant increase in plasma insulin levels. In addition, the diabetic rats had decreased levels of plasma total protein, albumin, globulin and albumin/globulin ratio as compared to control rats. After treatment with tetrahydrocurcumin and curcumin total protein, albumin, globulin and albumin/globulin ratio were brought back to near normal. The activities of hepatic and renal markers were significantly elevated in diabetic rats as compared to control rats, and treatment with tetrahydrocurcumin and curcumin has reversed these parameters to near normal levels. In diabetic rats, the decreased levels of urea, uric acid and creatinine with increased levels of albumin and urine volume was observed, and treatment with tetrahydrocurcumin and curcumin reversed these parameters to near normal. Tetrahydrocurcumin appeared to have a better protective effect when compared to curcumin. PMID- 17845506 TI - Oral supplementation of Majun Baladar ameliorates antioxidant enzyme activities in cerebral ischaemic damage. AB - Majun Baladar (MB), a traditional herbal formulation of the Unani system of medicine, was studied for its efficacy against cerebral ischaemia-induced oxidative damage in hippocampus and associated neurobehavioural deficits. Adult male Wistar rats were divided into four groups. The first group was sham, the second group was ischaemic (MCAO: middle cerebral artery occluded) and the third group was a MB pre-treated ischaemic group (MCAO + MB). The fourth group was given MB (1.05 g/kg) orally for 15 days as a drug control. The middle cerebral artery was occluded for 2 hr and reperfused for 22 hr in the ischaemic as well as the drug pre-treated group. The activity of the various enzymatic antioxidants like glutathione peroxidase, glutathione reductase, glutathione S-transferase and non-enzymatic antioxidants, glutathione along with levels of lipid peroxidation were evaluated. Cerebral ischaemic rats showed elevated level of lipid peroxidation and decreased levels of various antioxidants significantly over sham values. As a result of MB pre-treatment, the level of lipid peroxidation was found to be significantly depleted as compared to the ischaemic group. Furthermore, depleted levels of glutathione and the activity of glutathione peroxidase, glutathione S-transferase and glutathione reductase were restored significantly in MB treated group. Majun Baladar exhibited a significant improvement in neurobehavioural activities in the drug pre-treated animals as compared to the ischaemic group as evidenced by the grip strength test, Rota-Rod and video path analysis. The results of the present study provide baseline information regarding the neuroprotective efficacy of MB and also open a window for a potent therapeutic use of this traditional herbal Unani medicine. PMID- 17845507 TI - Chalcone arrests cell cycle progression and induces apoptosis through induction of mitochondrial pathway and inhibition of nuclear factor kappa B signalling in human bladder cancer cells. AB - Chalcones (1,3-diphenyl-2-propenone) are cancer preventive food components found in a human diet rich in fruits and vegetables. In this study, we first report the chemopreventive effect of chalcone in two human bladder cancer cell lines: T24 and HT-1376. The results show that chalcone inhibits the proliferation of T24 and HT-1376 cells by inducing apoptosis and blocking cell cycle progression in the G2/M phase. Western blot assay showed that chalcone significantly increases the expression of p21 and p27 proteins, and decreases the levels of cyclin B1, cyclin A and Cdc2, thereby contributing to cell cycle arrest. In addition, chalcone increased the expression of Bax and Bak, but decreased the levels of Bcl-2 and Bcl-X(L) and subsequently triggered mitochondrial apoptotic pathway (release of cytochrome c and activation of caspase-9 and caspase-3). Our study suggests that the induction of mitochondrial pathway and inhibition of the nuclear factor kappa B survival system may play important roles in the antiproliferative activity of chalcone in T24 and HT-1376 cells. PMID- 17845508 TI - Silymarin prevents palmitate-induced lipotoxicity in HepG2 cells: involvement of maintenance of Akt kinase activation. AB - Whereas adipocytes have a unique capacity to store excess free fatty acids in the form of triglyceride in lipid droplets, non-adipose tissues, such as liver, have a limited capacity for storage of lipids. Saturated long-chain fatty acids, such as palmitate, are the major contributors to lipotoxicity. Silymarin is a mixture of flavonolignans, extracted from the milk thistle (Silibum marianum). Its hepatoprotective properties have been studied both in vitro and in vivo; however, its effect on palmitate-induced lipotoxicity has not been investigated. The objective of this study was to investigate (i) whether silymarin could protect HepG2 cells from palmitate-induced cell death in an in vitro model, and (ii) possible mechanisms involved in this hepatoprotective role of silymarin. HepG2 cells were treated with palmitate in the absence or presence of silymarin and supernatants or cell lysates were collected at varying time-points. Cell death was assayed by measuring DNA fragmentation, caspase-3 activity and lactate dehydrogenase release. Lipid peroxidation was assessed by measuring malondialdehyde and 4-hydroxyalkenals. Akt kinase activity was also measured. Incubation with palmitate caused significant death in HepG2 cells. Palmitate incubation did not cause significant changes in reactive oxygen species production or intracellular glutathione content, but markedly inhibited Akt kinase activity. Pre-treatment of HepG2 cells with silymarin prevented palmitate induced inhibition of Akt kinase activity and attenuated cell death. Our results suggest that silymarin may be an effective agent in protecting hepatocytes from saturated fatty acids-induced cell death. These data also provide a further rationale for exploration of the use of silymarin in the treatment of non alcoholic steatohepatitis. PMID- 17845509 TI - Bursts of potential elicited by d-amphetamine in central snail neuron: effect of sodium azide. AB - Effects of sodium azide (NaN(3)) on spontaneously generated action potential and bursts of potential elicited by d-amphetamine (d-amphetamine-elicited BoP) were studied on the right parietal 4 (RP4) neuron of the snail Achatina fulica Ferussac in vitro. Sodium azide altered the spontaneous action potential of RP4 neuron in a concentration-dependent manner. In lower concentrations, neither NaN(3) (30, 100, 300 microM; 1 and 3 mM) nor d-amphetamine (135 microM) affect the resting membrane potential, amplitude and frequency of RP4 neurons, while in the higher concentrations NaN(3) (30 mM) did abolish the spontaneous action potential on RP4 neurons and depolarized the RP4 neurons reversibly. At lower concentration, NaN(3) (30 microM) facilitated the d-amphetamine-elicited BoP. The BoP elicited by NaN(3) (30 microM) and d-amphetamine (135 microM) were decreased following treatment with KT5720 (protein kinase A inhibitor), or intracellular injection of EGTA [ethylene glycol-bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid]. However, the BoP was not affected by applying U73122 (1-[6-[((17beta)-3 methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione) or neomycin (phospholipase inhibitors). Voltage clamp studies revealed that NaN(3) (30 microM) did not alter the total fast inwards currents (70 msec.) and the steady state outwards currents (5 sec.). It appeared that the BoP elicited by NaN(3) (30 microM) and d-amphetamine (135 microM) was mainly due to protein kinase A-related messenger system and intracellular calcium. It is concluded that d-amphetamine elicited BoP was not mainly due to inhibition of the function of mitochondria in the neuron while the function of mitochondria did alter the BoP elicited by amphetamine. PMID- 17845510 TI - Effect of betulinic acid on anticancer drug-resistant colon cancer cells. AB - Primary or acquired resistance of tumours to established chemotherapeutic regimens is a major concern in oncology. Attempts to improve the survival of cancer patients largely depend on strategies to prevent tumour cell resistance. 5 Fluorouracil (5-FU)-based chemotherapy with a combination of other drugs such as irinotecan (IRT) and oxaliplatin (OXT) has been reported to be effective, even though an optimal regimen has yet to be defined due to the relatively high toxicity of the procedure. The aim of this study was to examine the effect of betulinic acid (BetA) as a chemosensitizer for anticancer drug treatment in chemoresistant colon cancer cell lines. A chemoresistant cell line to 5 fluorouracil (SNU-C5/5FU-R), irinotecan (SNU-C5/IRT-R) and oxaliplatin (SNU C5/OXT-R) treatment were derived from the wild-type colon adenocarcinoma cell line (SNU-C5/WT). The effect of BetA or a combination of anticancer drugs and BetA on the multidrug resistance-related genes, caspases, Bcl-2, Bad and cell death in the SNU-C5/WT and SNU-C5/R cell lines was analysed. BetA alone was an effective chemotherapeutic drug for the SNU-C5/WT, SNU-C5/5FU-R and SNU-C5/OXT-R cells. The combination of BetA with IRT or OXT was effective against SNU-C5/5FU-R cells, and the combination of BetA with 5-fluorouracil, IRT or OXT was effective against SNU-C5/OXT-R cells. BetA induced cancer cell death by apoptosis through the mitochondrial pathway. These findings indicate that the use of BetA as a chemosensitizer may be a new strategy to enhance the efficacy of chemotherapy. However, further studies will be needed for confirmation. PMID- 17845512 TI - Poriferan ANTP genes: primitively simple or secondarily reduced? PMID- 17845513 TI - Phylogenetic distribution of microRNAs supports the basal position of acoel flatworms and the polyphyly of Platyhelminthes. AB - Phylogenetic analyses based on gene sequences suggest that acoel flatworms are not members of the phylum Platyhelminthes, but instead are the most basal branch of triploblastic bilaterians. Nonetheless, this result has been called into question. An alternative test is to use qualitative molecular markers that should, in principle, exclude the possibility of convergent (homoplastic) evolution in unrelated groups. microRNAs (miRNAs), noncoding regulatory RNA molecules that are under intense stabilizing selection, are a newly discovered set of phylogenetic markers that can resolve such taxonomic disputes. The acoel Childia sp. has recently been shown to possess a subset of the conserved core of miRNAs found across deuterostomes and protostomes, whereas a polyclad flatworm-in addition to this core subset-possesses miRNAs restricted to just protostomes. Here, we examine another acoel, Symsagittifera roscoffensis, and three other platyhelminths. Our results show that the distribution of miRNAs in S. roscoffensis parallels that of Childia. In addition, two of 13 new miRNAs cloned from a triclad flatworm are also found in other lophotrochozoan protostomes, but not in ecdysozoans, deuterostomes, or in basal metazoans including acoels. The limited set of miRNAs found in acoels, intermediate between the even more reduced set in cnidarians and the larger and expanding set in the rest of bilaterians, is compelling evidence for the basal position of acoel flatworms and the polyphyly of Platyhelminthes. PMID- 17845514 TI - Brefeldin A and monensin inhibit the D quadrant organizer in the polychaete annelids Arctonoe vittata and Serpula columbiana. AB - The D quadrant organizer is a developmental signaling center that is localized to the vegetal D quadrant in different spiral-cleaving lophotrochozoan embryos and may be homologous to axial organizing regions in other metazoans. Patterning by this organizing center creates a secondary developmental axis and is required for the transition from spiral to bilateral cleavage and later establishment of the adult body plan. Organizer specification in equal-cleaving embryos is thought to involve inductive interactions between opposing animal and vegetal blastomeres. To date, experimental demonstration of this interaction has been limited to molluscs and nemerteans. Here, we examine three families of equal-cleaving polychaete annelids for evidence of animal-vegetal contact. We find that contact is present in the polynoid, Arctonoe vittata, but is absent in the serpulid, Serpula columbiana, and in the oweniid, Oweniia fusiformis. To interfere with cell signaling during the period predicted for organizer specification and patterning in A. vittata and S. columbiana, we use two general inhibitors of protein processing and secretion: Brefeldin A (BFA) and monensin. In A. vittata, we detail subsequent embryonic and larval adult development and show that treatment with either chemical results in radialization of the embryo and subsequent body plan. Radialized larvae differentiate many larval and adult structures despite the loss of bilateral symmetry but do so in either a radially symmetric or four-fold radially symmetric fashion. Our results suggest that the D quadrant organizer is functionally conserved in equal-cleaving polychaetes, but that details of its specification, induction, and patterning have diverged relative to other spiral-cleaving phyla. PMID- 17845515 TI - Apical organs in echinoderm larvae: insights into larval evolution in the Ambulacraria. AB - The anatomy and cellular organization of serotonergic neurons in the echinoderm apical organ exhibits class-specific features in dipleurula-type (auricularia, bipinnaria) and pluteus-type (ophiopluteus, echinopluteus) larvae. The apical organ forms in association with anterior ciliary structures. Apical organs in dipleurula-type larvae are more similar to each other than to those in either of the pluteus forms. In asteroid bipinnaria and holothuroid auricularia the apical organ spans ciliary band sectors that traverse the anterior-most end of the larvae. The asteroid apical organ also has prominent bilateral ganglia that connect with an apical network of neurites. The simple apical organ of the auricularia is similar to that in the hemichordate tornaria larva. Apical organs in pluteus forms differ markedly. The echinopluteus apical organ is a single structure on the oral hood between the larval arms comprised of two groups of cells joined by a commissure and its cell bodies do not reside in the ciliary band. Ophioplutei have a pair of lateral ganglia associated with the ciliary band of larval arms that may be the ophiuroid apical organ. Comparative anatomy of the serotonergic nervous systems in the dipleurula-type larvae of the Ambulacraria (Echinodermata+Hemichordata) suggests that the apical organ of this deuterostome clade originated as a simple bilaterally symmetric nerve plexus spanning ciliary band sectors at the anterior end of the larva. From this structure, the apical organ has been independently modified in association with the evolution of class specific larval forms. PMID- 17845516 TI - Characterization of the expression patterns of LEAFY/FLORICAULA and NEEDLY orthologs in female and male cones of the conifer genera Picea, Podocarpus, and Taxus: implications for current evo-devo hypotheses for gymnosperms. AB - The identity of genes causally implicated in the development and evolutionary origin of reproductive characters in gymnosperms is largely unknown. Working within the framework of plant evolutionary developmental biology, here we have cloned, sequenced, performed phylogenetic analyses upon and tested the expression patterns of LEAFY/FLORICAULA and NEEDLY orthologs in reproductive structures from selected species of the conifer genera Picea, Podocarpus, and Taxus. Contrary to expectations based on previous assessments, expression of LFY/FLO and NLY in cones of these taxa was found to occur simultaneously in a single reproductive axis, initially overlapping but later in mutually exclusive primordia and/or groups of developing cells in both female and male structures. These observations directly affect the status of the "mostly male theory" for the origin of the angiosperm flower. On the other hand, comparative spatiotemporal patterns of the expression of these genes suggest a complex genetic regulatory network of cone development, as well as a scheme of functional divergence for LFY/FLO with respect to NLY homologs in gymnosperms, both with clear heterochronic aspects. Results presented in this study contribute to the understanding of the molecular genetic basis of morphological evolution in conifer cones, and may aid in establishing a foundation for gymnosperm-specific, testable evo-devo hypotheses. PMID- 17845517 TI - Constraints and selection: insights from microsporogenesis in Asparagales. AB - Developmental constraints have been proposed to interfere with natural selection in limiting the available set of potential adaptations. Whereas this concept has long been debated on theoretical grounds, it has been investigated empirically only in a few studies. In this article, we evaluate the importance of developmental constraints during microsporogenesis (male meiosis in plants), with an emphasis on phylogenetic patterns in Asparagales. Different developmental constraints were tested by character reshuffling or by simulated distributions. Among the different characteristics of microsporogenesis, only cell wall formation appeared as constrained. We show that constraints may also result from biases in the correlated occurrence of developmental steps (e.g., lack of successive cytokinesis when wall formation is centripetal). We document such biases and their potential outcomes, notably the establishment of intermediate stages, which allow development to bypass such constraints. These insights are discussed with regard to potential selection on pollen morphology. PMID- 17845518 TI - Combining ontogenetic and evolutionary scales of morphological disparity: a study of early Jurassic ammonites. AB - Two major research themes in Evolutionary Developmental Biology and in Paleobiology, respectively, have each become central for the analysis and interpretation of morphological changes in evolution: the study of ontogeny/phylogeny connections, mainly within the widespread and controversial framework of heterochrony; and the study of morphological disparity, the morphological signal of biodiversity, describing secular changes in morphospace occupation during the history of any given clade. Although enriching in their respective fields, these two themes have remained rather isolated to date, despite the potential value of integrating them as some recent studies begin to suggest. Here, we explore the recent notion of developmental morphospace morphospace carrying ontogenetic information-as a potential tool for bridging the gap between disparity dynamics and developmental dynamics. We elaborate this approach with a case study of Early Jurassic ammonite family Hildoceratidae (Mollusca, Cephalopoda). Morphometric analyses of the shell shape of 20 species spanning the morphological spectrum of the family are used to quantify and contrast juvenile and adult disparity levels. Adult disparity is significantly greater than juvenile disparity at the family level; yet, some subclades also display different patterns. In addition, comparisons of ontogenetic trajectories underline the prevalence of heterochrony-based evolutionary modifications within subfamilies (via ontogenetic scaling); they also point to the probable existence of pervasive developmental constraints structuring inhomogeneous morphospace occupation. PMID- 17845519 TI - Evaluating paedomorphic heterochrony in trilobites: the case of the diminutive trilobite Flexicalymene retrorsa minuens from the Cincinnatian Series (Upper Ordovician), Cincinnati region. AB - Flexicalymene retrorsa minuens from the uppermost 3 m of the Waynesville Formation of the Cincinnatian Series (Upper Ordovician) of North America lived approximately 445 Ma and exhibited marked reduction in maximum size relative to its stratigraphically subjacent sister subspecies, Flexicalymene retrorsa retrorsa. Phylogenetic analysis is consistent with the notion that F. retrorsa retrorsa was the ancestor of F. retrorsa minuens. F. retrorsa minuens has been claimed to differ from F. retrorsa retrorsa"in size alone," and thus presents a plausible example of global paedomorphic evolution in trilobites. Despite strong similarity in the overall form of the two subspecies, F. retrorsa minuens is neither a dwarf nor a simple progenetic descendant of F. retrorsa retrorsa. More complex patterns of global heterochronic paedomorphosis, such as a neotonic decrease in the rate of progress along a common ontogenetic trajectory with respect to size, coupled with growth cessation at a small size, "sequential" progenesis, or non-uniform changes in the rate of progress along a shared ontogenetic trajectory with respect to size, can also be rejected. Rather, differences between these subspecies are more consistent with localized changes in rates of character development than with a global heterochronic modification of the ancestral ontogeny. The evolution of F. retrorsa minuens from F. retrorsa retrorsa was largely dominated by modifications of the development of characters already evident in the ancestral ontogeny, not by the origin of novel structures. Factors promoting size reduction in F. retrorsa minuens appear to have been specific to this subspecies, because other co-occurring taxa, including other trilobite species, do not show marked differences in mean size. PMID- 17845520 TI - Endocrine analysis in evolutionary-developmental studies of insect polymorphism: hormone manipulation versus direct measurement of hormonal regulators. AB - "Hormone manipulation" is being used increasingly in evo-devo studies as the sole or primary technique to investigate the regulation of insect polymorphism by hormones, most notably juvenile hormone (JH). This manuscript critically evaluates the limitations and strengths of this indirect method for inferring aspects of endocrine regulation, and conclusions derived from recent endocrine studies of evolution and development in which data have been obtained primarily or exclusively by this method. The main conclusions of this critique are as follows: first, when used alone, or as the primary empirical technique, hormone manipulation is a superficial method that is fraught with problems with respect to identifying a hormone that regulates developmental-morphological variation, let alone identifying its mode of action. Second, conclusions reported in studies using this technique as the exclusive, or nearly exclusive experimental approach, most notably recent studies of JH regulation of horn polymorphism in dung beetles, and some studies of wing polymorphism should be considered, at best, weakly supported until substantiated by well-validated, direct methods. Finally, there are many reliable and well-validated techniques that can be used to directly and accurately quantify JH levels, and activities of JH regulators, in many insects, even in small, nonmodel species. Some of the most important of these assays will be briefly described and their strengths and weaknesses will be discussed. PMID- 17845524 TI - What's love got to do with it? Sexual behaviors of opposite-sex couples through emerging adulthood. AB - CONTEXT: Sexual relationships in young adulthood may have important ramifications for individuals' physical and emotional well-being. Nonetheless, representative information about young adults' sexual activities in long-term relationships and the emotional context of such relationships is rare. METHODS: A subsample of 6,421 participants in Wave 3 of the National Longitudinal Study of Adolescent Health (18-26-year-olds) who were in a sexual relationship of at least three months' duration were selected for analysis. Multiple logistic regression models were used to explore the relationship between love and various sexual activities. RESULTS: Eighty percent of respondents had engaged in cunnilingus and fellatio as well as vaginal intercourse in their current relationship; this group included 22% who also had engaged in anal sex. Compared with their peers who reported that they and their partner did not love each other a lot, both males and females who reported mutually loving relationships had significantly higher odds of having given oral sex (odds ratios, 3.9 and 2.6, respectively) and having received oral sex (1.8 and 3.3); males in mutually loving relationships also had elevated odds of having had anal sex (3.1). CONCLUSIONS: Most young adult couples in long-term relationships engage in a variety of sexual practices with loving partners; the direction of causality in this association and its implications for relationship building require exploration. Furthermore, programs and interventions that address health and well-being during emerging adulthood should cover issues relevant to a broad range of sexual activities, including oral and anal sex. PMID- 17845525 TI - Using clinical classification trees to identify individuals at risk of STDs during pregnancy. AB - CONTEXT: Few studies have used classification tree analysis to produce empirically driven decision tools that identify subgroups of women at risk of STDs during pregnancy. Such tools can guide care, treatment and prevention efforts in clinical settings. METHODS: A sample of 647 women aged 14-25 attending two urban obstetrics and gynecology clinics in 2001-2004 were surveyed in their second and third trimesters. Baseline predictors at the individual, dyad, and family and community levels were used to develop a classification tree that differentiated subgroups of women by STD incidence at 35 weeks' gestation. Logistic regression analyses were conducted to assess whether the classification tree groups or commonly used risk factors better predicted STD incidence. RESULTS: Nineteen percent of women had an incident STD during pregnancy. Classification tree analysis identified three subgroups with a high STD incidence (33-61%), one with a moderate incidence (16%) and three with a low incidence (6 11%). Women in subgroups with high STD incidence included those not living with the partner with whom they conceived and those who had a moderate or a high level of depression, a history of STDs and a low level of social support. A logistic regression model using groups defined by the classification tree analysis had better predictive ability than one using common demographic and sexual risk predictors. CONCLUSION: This classification tree identified risk factors not captured by traditional risk screenings, and could be used to guide STD treatment, care and prevention within the prenatal care setting. PMID- 17845526 TI - Adolescents' discussions about contraception or STDs with partners before first sex. AB - CONTEXT: Limited research has examined the individual, family and relationship factors that determine whether teenagers discuss contraception or STDs with their sexual partners before having sex for the first time. METHODS: Logistic regression analyses of data from 1,426 teenagers who participated in Waves 1 (1995) and 2 (1996) of the National Longitudinal Study of Adolescent Health and who had first sex between waves examined factors influencing whether respondents discussed contraception or STDs with their partner before first sex, and whether these factors differ by gender. RESULTS: Fifty-three percent of females and 45% of males discussed contraception or STDs before having first sex. The greater respondents' perceived condom knowledge and the greater their communication with their parents about everyday life, the higher their odds of discussing contraception or STDs before first sex (odds ratio, 1.2 for each). Being black was positively associated with sexual communication before first sex (1.9); as the number of dating activities and score on a test of verbal ability increased, so did the odds of such communication (1.6 and 1.02, respectively). The predictors of discussions about contraception or STDs did not differ by gender. CONCLUSIONS: By increasing teenagers' knowledge about condoms and other methods of contraception, pregnancy and STD prevention programs can help to encourage communication among teenage partners before the initiation of sexual intercourse. Programs should also encourage conversations between parents and teenagers, even when not about sex. PMID- 17845527 TI - Characteristics associated with emergency contraception use by family planning patients: a prospective cohort study. AB - CONTEXT: Little is known about how written family planning clinic policy regarding emergency contraception, as well as personal characteristics, behaviors and attitudes, may influence a woman to use emergency contraception. METHODS: Between June 2001 and July 2002, women attending publicly funded family planning clinics in Pennsylvania were enrolled in an 18-month longitudinal study. Half attended clinics with a policy of offering emergency contraception in advance; the remainder had only emergent access to the drug. After providing baseline data, women completed monthly automated phone surveys about recent sexual activity, contraceptive use and attitudes toward pregnancy. Characteristics associated with recent use of emergency contraception were examined using multivariate logistic regression. RESULTS: Responses to 3,700 phone surveys from 729 women showed that 25% of those who attended clinics offering advance access used emergency contraception at least once during the study, compared with 8% who attended emergent access clinics. Women attending advance access clinics had significantly elevated odds of having used emergency contraception in the past month (odds ratio, 2.6). Other characteristics positively associated with the likelihood of recent emergency contraception use were familiarity with the drug, having a new sex partner and having unprotected sex at least once (2.0 each); negative feelings toward pregnancy (1.4); and using condoms as one's main contraceptive method (1.8). CONCLUSIONS: In addition to discussing and offering advance emergency contraception, providers should further explore specific behaviors and attitudes associated with emergency contraception use. PMID- 17845528 TI - California parents' preferences and beliefs regarding school-based sex education policy. AB - CONTEXT: Policy debates over the merits of abstinence-only versus comprehensive approaches to sex education are ongoing, despite well-documented public support for comprehensive sex education. Although parents are key stakeholders in the outcomes of these debates, their views have been less thoroughly considered. METHODS: A random digit dial survey of 1,284 California parents was conducted in 2006. Parents were asked about their sex education policy preferences, the importance of teaching selected topics at different grade levels and reasons for their preferences. Cross-tabulations and odds ratios were used to assess regional and other subgroup differences. RESULTS: Overall, 89% of parents reported a preference for comprehensive sex education, and 11% for abstinence-only education. Support for comprehensive sex education was high in all regions (87 93%) and across all subgroup characteristics: race or ethnicity (79-92%), age (86 94%), education (84-93%), household income (87-92%), religious affiliation (86 91%), religious service attendance (69-96%) and ideological leaning (71-96%). Four types of reasons for preferences emerged: those focused on the consequences of actions, on the importance of providing complete information, on the inevitability of adolescents' engaging in sex and on religious or purity-based morality concerns. While 64% of abstinence-only supporters cited the last type (absolutist reasons), 94% of comprehensive sex education supporters cited one of the first three (pragmatic reasons). CONCLUSIONS: The high levels of support for comprehensive sex education across California's diverse regions and demographic subgroups suggest that such support may be generalizable to communities and school districts both in California and around the country. Furthermore, ideological differences might be less important to the sex education debates than the distinction between pragmatic and absolutist perspectives. PMID- 17845529 TI - Developing Spanish-language family planning materials: lessons learned from extensive field tests. PMID- 17845530 TI - Oncoproteomics of hepatocellular carcinoma: from cancer markers' discovery to functional pathways. AB - Hepatocellular carcinoma (HCC) is a heterogeneous cancer with no promising treatment and remains one of the most prevailing and lethal malignancies in the world. Researchers in many biological areas now routinely identify and characterize protein markers by a mass spectrometry-based proteomic approach, a method that has been commonly used to discover diagnostic biomarkers for cancer detection. The proteomic research platforms span from the classical two dimensional polyacrylamide gel electrophoresis (2-DE) to the latest Protein Chip or array technology, which are often integrated with the MALDI (matrix-assisted laser-desorption ionization), SELDI (surface-enhanced laser desorption/ionization) or tandem mass spectrometry (MS/MS). New advances on quantitative proteomic analysis (e.g. SILAC, ICAT, and ITRAQ) and multidimensional protein identification technology (MudPIT) have greatly enhanced the capability of proteomic methods to study the expressions, modifications and functions of protein markers. The present article reviews the latest proteomic development and discovery of biomarkers in HCC that may provide insights into the underlying mechanisms of hepatocarcinogenesis and the readiness of biomarkers for clinical uses. PMID- 17845531 TI - Apoptosis in the liver: a matter of ion fluxes and oxidative stress: Third International Conference of the Collaborative Research Center 'Experimental Hepatology' (SFB-575), Dusseldorf, Germany, 13-14 October 2006. AB - The cell death of hepatocytes is a characteristic feature of liver damage triggered by viral infection, drug abuse, fat overload or autoimmunity. Apoptosis is currently the best-understood form of cell death; however, the precise mechanisms leading to apoptosis in liver disease are largely unknown. Several cellular processes including alterations in cell hydration and ion homeostasis, osmotic and oxidative stress, lysosomal permeabilization as well as alternate forms of cell death may contribute to liver damage. The intriguing complexity and relevance of these processes for liver failure were addressed at the Third International Conference of the Collaborative Research Center 'Experimental Hepatology' (SFB-575),which was held in Dusseldorf, Germany, in 13-14 October 2006. The aim of this symposium was to bring together leading researchers studying cell death pathways in the liver and other systems and to share ideas and recent research findings. This report covers some of the salient and stimulating contributions of the meeting and gives an updated survey of the advances in this burgeoning field of translational medicine. PMID- 17845532 TI - Role of Ca2+-dependent potassium channels in in vitro anandamide-mediated mesenteric vasorelaxation in rats with biliary cirrhosis. AB - BACKGROUND/AIM: Anandamide can activate potassium (K(+)) channels to induce an endothelium-dependent vasorelaxation in normal rat mesenteric arteries. Cannabinoids contribute partly to the splanchnic vasodilation in cirrhosis. This study investigated the roles of vascular K(+) channels in anandamide-induced mesenteric vasorelaxation in isolated rat cirrhotic vessels. METHODS: The effects of the pretreatment of AM251, a specific CB(1) receptor antagonist, were assessed on the vascular reactivity to phenylephrine (PE), potassium chloride (KCl), acetylcholine (ACh) and sodium nitroprusside (SNP). Additionally, cannabinoid (CB(1) and CB(2)) receptors' protein expression and the effects of different K(+) channel blockers on vascular reactivity to anandamide were also studied. RESULTS: Cirrhotic mesenteric arteries showed an overexpression of CB(1) receptor associated with hyporeactivity to PE and KCl, and hyper-response to ACh, SNP and anandamide. Pretreatment with AM251 significantly improved the hyporeactivity to KCl and ameliorated the hyper-response to ACh in cirrhotic vessels. Increased relaxation response to anandamide was suppressed by combinations of vascular Ca(2+)-dependent K(+) channel blockers (including apamin+charybdotoxin+iberiotoxin or apamin+TRAM-34+iberiotoxin) (TRAM-34, 1-[(2 chlorophenyl)diphenylmethyl]-1H-pyrazole). CONCLUSIONS: In cirrhotic mesenteric arteries, vascular CB(1) receptor and anandamide contribute to the in vitro hyporeactivity to KCl. In addition, hyper-response to ACh may probably act through the modulation of vascular Ca(2+)-dependent K(+) channels. PMID- 17845533 TI - Extrahepatic cholestasis downregulates Oatp1 by TNF-alpha signalling without affecting Oatp2 and Oatp4 expression and sodium-independent bile salt uptake in rat liver. AB - Hepatic uptake of bile salts is mediated by sodium-dependent and sodium independent transport systems. During extrahepatic cholestasis, both the function and the expression of the Na(+)/taurocholate cotransporting polypeptide (Ntcp) are downregulated. To test whether sodium-independent organic anion-transporting polypeptides are also affected by extrahepatic cholestasis, the function and expression of all three Oatps have been determined in common bile duct-ligated (CBDL) rats. Oatp1/Oatp1a1 protein mass remained unchanged after CBDL for 1 day, but then declined by 75+/-7% and 90+/-17%, respectively, after 3 and 7 days. In contrast, Oatp2/Oatp1a4 and Oatp4/Oatp1b2 protein expression was not affected by CBDL as compared with controls. After CBDL, Oatp1 mRNA was rapidly downregulated by 68+/-21% of untreated controls (P<0.05) within 24 h, and remained at similar levels at 3 and 7 days. Cytokine-inactivation studies with etanercept pretreatment demonstrated that TNF-alpha-dependent signals mediated the down regulation of this transporter gene at both protein and mRNA levels during obstructive cholestasis. Sodium-independent uptake of taurocholate and cholate into freshly isolated hepatocyte suspensions showed neither significant differences in K(m) nor V(max) values. These results indicate that sodium independent transport of bile salts may be mediated by Oatp2 and 4 during biliary obstruction, because its expression remains unaffected and may compensate for loss of Oatp1 expression and function in cholestatic hepatocytes. PMID- 17845534 TI - Effect of phorbol ester and platelet-derived growth factor on protein kinase C in rat hepatic stellate cells. AB - BACKGROUND/AIMS: Hepatic stellate cells (HSC) play a key role in hepatic fibrogenesis and thus, it is important to understand the intracellular signalling pathways that influence their behaviour. This study investigated the expression and regulation of protein kinase C (PKC) in HSC. RESULTS: Western blot analysis indicates that rat HSC express at least four PKC isoforms, PKC-alpha, PKC-delta, PKC-epsilon and PKC-zeta. PKC-alpha and PKC-zeta were located predominantly in the cytosol and were redistributed to the membrane by the PKC agonist, phorbol 12 myristate 13-acetate (PMA), while PKC-delta and PKC-epsilon were highly membrane bound and did not undergo translocation by PMA. PKC-alpha, PKC-delta and PKC-zeta were rapidly downregulated by PMA. However, PKC-epsilon was resistant to downregulation. We also examined phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS), a specific substrate of PKC, as another approach to assess activation of PKC. Platelet-derived growth factor (PDGF) and PMA increased the phosphorylation of MARCKS, suggesting that PDGF can induce PKC activation. PDGF-induced stimulation of extracellular signal-regulated kinase, phosphatidylinositol 3-kinase and p70-S6 kinase was not abrogated by downregulation of PKC-alpha, PKC-delta and PKC-zeta. Prolonged PKC inhibition did not inhibit the fibrogenic phenotype. CONCLUSION: Multiple PKC isoforms are expressed in rat HSC and are differentially regulated by PMA. PDGF activates certain mitogenic signalling pathways independent of PKC-alpha, PKC-delta and PKC zeta. Specific PKC isoforms may modulate different cell functions in HSC. PMID- 17845535 TI - Significance of morphological alteration by portal vein branch ligation in endotoxin-induced liver injury after partial hepatectomy. AB - BACKGROUND: Regenerating liver after partial hepatectomy (PH) is susceptible to endotoxin. This study was conducted to investigate how morphological alteration by preoperative portal vein branch ligation (PVL) affects endotoxin-induced liver injury after PH. METHODS: Male Sprague-Dawley rats were divided into a PVL group undergoing left PVL and into a non-PVL group receiving a sham operation. Seven days later, animals in both groups were subjected to PH (the left lateral, median and caudate lobes). Lipopolysaccharide (LPS) was intravenously administered to both groups 2 days after PH. RESULTS: A significant increase in hepatocyte and sinusoidal endothelial cell proliferation assessed by Ki-67 immunostaining reached a peak at day 2 and 3 after PVL, respectively, in accordance with the changes in plasma interleukin-6 concentrations after PVL. The proliferation response of these cells after PH was observed in both groups, showing a significantly weaker response in the PVL group. The sinusoidal width after PH was significantly reduced in the non-PVL group when compared with that in the PVL group. LPS administration induced a marked elevation of plasma tumour necrosis factor-alpha levels in the non-PVL group compared with the PVL group. PVL before PH significantly attenuated endotoxin-induced functional and structural liver damage with greater hepatic polymorphonuclear leucocyte infiltration and microcirculatory derangement, resulting in an improvement in the 7-day survival rate. CONCLUSIONS: Morphological alteration by PVL is of great advantage in preventing the development of endotoxin-induced liver injury in the regeneration process after PH. PMID- 17845536 TI - Development of autoimmune hepatitis in primary biliary cirrhosis. AB - AIM/BACKGROUND: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown aetiology. Up to 10% of patients with typical features of PBC will have additional features of autoimmune hepatitis (AIH). A subset, however, have no such features but go on to develop a 'sequential' AIH overlap syndrome. OBJECTIVES: Describe our experience with eight patients who developed AIH after the diagnosis of PBC was made. METHODS: We reviewed the charts of all PBC patients over a 9-year period (from 1996 to 2005). Only PBC patients with no features of AIH were included. RESULTS: There were 1476 patients with PBC. Of these, eight patients developed features of AIH overlap syndrome based on biochemical and histological parameters. Treatment included prednisone and azathioprine for 24 or more months. The majority of patients remained on ursodeoxycholic acid (UDCA) throughout treatment. Response to therapy was defined by improvement in enzymes, and was rapid for all patients. One patient was able to discontinue treatment with prednisone and azathioprine, while seven have continued on therapy to date. CONCLUSIONS: A 'sequential' overlap syndrome of AIH with PBC can occur. Treatment with prednisone and azathioprine may lead to a rapid improvement in aminotransferase levels. PMID- 17845537 TI - Serum C-reactive protein levels predict survival in hepatocellular carcinoma. AB - BACKGROUND/AIMS: C-reactive protein (CRP) was recently identified as a prognostic factor for patients with hepatocellular carcinoma (HCC) after surgical resection. We investigated the relationship between the serum levels of high sensitivity CRP (H-CRP) and the prognosis of HCC patients. METHOD: We conducted a cohort study of 90 HCC patients enrolled from 1997 to 1998. All patients were treated and followed for a mean period of 3.2 years. Clinical variables were compared between patients positive for H-CRP (serum H-CRP levels >/=3.0 mg/L, n=47) and those negative for H-CRP (serum H-CRP levels <3.0 mg/L, n=43). We also determined the relationship between serum H-CRP and prognosis in HCC patients. RESULTS: The survival rate of patients of the H-CRP-positive group was lower than that of H CRP-negative patients. Tumour stage (stages 3 or 4), total bilirubin >/=1.2 mg/dL, albumin (Alb) <3.5 g/dL, des-gamma-carboxy prothrombin >/=40 mAU/mL, positive H-CRP and initial treatment (transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy or best supportive care) were identified as significant poor prognostic factors by univariate analysis, while positive H CRP [hazard ratio (HR), 1.58; P=0.048], Alb<3.5 g/dL (HR, 2.10; P=0.004), tumour stage (stages 3 or 4; HR, 3.05; P=0.001) and initial treatment (HR, 1.88; P=0.029) were considered to be significant determinants of poor prognosis by multivariate Cox proportional hazards analysis. CONCLUSIONS: The prognosis of H CRP-positive patients was poorer compared with H-CRP-negative patients. This study confirmed that H-CRP, like CRP, is a marker of poor prognosis in HCC patients. PMID- 17845538 TI - Incidence of psychiatric side effects during pegylated interferon- alpha retreatment in nonresponder hepatitis C virus-infected patients. AB - OBJECTIVE: Evaluate the incidence of mental disorders using pegylated interferon plus ribavirin retreatment in nonresponder hepatitis C virus-infected patients. METHOD: The Mini-International Neuropsychiatric Interview (MINI) was used to evaluate 30 hepatitis C virus-infected interferon-nonresponder patients at baseline and following 4, 12 and 24 weeks of pegylated interferon retreatment. RESULTS: During the pegylated interferon/ribavirin retreatment, 5(16.6%) patients developed psychiatric side effects: 3(10%) were diagnosed with major depressive disorder, 1(3.3%) had a brief psychotic disorder and 1(3.3%) presented with panic attacks. CONCLUSION: This is the first prospective study evaluating the incidence of neuropsychiatric side effects during interferon retreatment of hepatitis C virus-infected patients, suggesting that the risk of acquiring serious psychiatric symptoms during retreatment with interferon-alpha (IFN-alpha) may not be higher than during the first antiviral therapy. This finding challenges the hypothesis that during a second treatment with IFN-alpha, patients with hepatitis C may be at greater risk for neuropsychiatric side effects than naive patients. PMID- 17845539 TI - Damping index of Doppler hepatic vein waveform to assess the severity of portal hypertension and response to propranolol in liver cirrhosis: a prospective nonrandomized study. AB - BACKGROUND AND AIMS: Alterations in the Doppler hepatic vein (HV) waveform are associated with cirrhosis and portal hypertension. We prospectively evaluated the correlation between the extent of abnormal Doppler HV waveforms expressed as damping index (DI) and the hepatic venous pressure gradient (HVPG) and response to propranolol in patients with cirrhosis. MATERIAL AND METHODS: In 76 patients with cirrhosis (69 men and seven women), both DI of Doppler HV waveform and HVPG were measured, and the relationship between them was analysed. DI was calculated by the minimum velocity/maximum velocity of the HV waveform. An HVPG>12 mmHg was defined as severe portal hypertension. In a subgroup of 19 patients receiving propranolol, changes in both DI and HVPG were evaluated after propranolol administration for 3 months. One author (S. K. B.) performed all DI of Doppler HV waveform studies. RESULTS: Abnormal HV waveforms were seen in 66 of 76 patients (86.8%). DI significantly correlated with the grade of HVPG, i.e. with higher HVPG increased DI was observed (P<0.01). By logistic regression analysis, DI>0.6 was significantly more likely to be severe portal hypertension (odds ratio: 14.19, 95% confidence interval: 4.07-49.55). Receiver-operating characteristic curve according to the value of 0.6 of DI showed a sensitivity of 75.9% and a specificity of 81.8% for the presence of severe portal hypertension. In 19 patients of the propranolol subgroup, change of DI following propranolol treatment also significantly correlated with that of HVPG (P<0.01). CONCLUSIONS: Damping index of the HV waveform by Doppler ultrasonography might be a non invasive supplementary tool in evaluating the severity of portal hypertension and in responding to propranolol in patients with liver cirrhosis. PMID- 17845540 TI - Efficacy of interferon alpha-2b induction therapy before retreatment for chronic hepatitis C. AB - BACKGROUND/AIMS: Chronic hepatitis C (HCV) patients who have failed previous treatment have low sustained viral response (SVR) rates with repeat treatment. We evaluated whether interferon (IFN) induction during retreatment improves response rates. METHODS: Two randomized, controlled trials were conducted in chronic HCV patients who failed IFN. In Study 1, patients received IFN 3 MU daily plus ribavirin (RBV) 1000 mg/day for 4 weeks, followed by IFN 3 MU TIW plus RBV 1000 mg/day for 44 weeks (induction; n=232), or IFN 3 MU TIW plus RBV 1000 mg/day for 48 weeks (non-induction; n=237). In Study 2, patients received IFN 5 MU B.I.D. plus RBV 1000-1200 mg/day for 2 weeks, followed by pegylated IFN (PEG-IFN) 75-150 mug weekly plus RBV 1000-1200 mg/day for 46 weeks (induction; n=201), or PEG-IFN 75-150 mug weekly plus RBV 1000-1200 mg/day for 48 weeks (non-induction; n=206). The primary end point for both trials was SVR. RESULTS: Induction did not increase SVR compared with non-induction, but did increase the on-treatment response among genotype non-1 patients in Study 2. By intention-to-treat (ITT) analysis, SVR in Study 1 was 13% for induction vs. 9% for non-induction (P=NS). In Study 2 (ITT), SVR was 20% for induction vs. 24% for non-induction (P=NS). However, by non-ITT analysis of Study 2, genotype non-1-previous non-responders showed significantly higher response rates with induction than non-induction. CONCLUSION: For chronic HCV patients who have failed IFN, induction with retreatment does not improve SVR, but may be beneficial for patients with genotype non-1 HCV. PMID- 17845541 TI - Health-related quality of life in patients with chronic hepatitis B. AB - Although chronic hepatitis C (CH-C) has consistently been shown to impair patients' health-related quality of life (HRQL), the impact of chronic hepatitis B (CH-B) on HRQL has not been fully explored. AIM: Compare HRQL between patients with CH-B, CH-C, primary biliary cirrhosis (PBC) and healthy controls. DESIGN: Three HRQL questionnaires [Chronic Liver Disease Questionnaire (CLDQ), Short Form 36 (SF-36) and the Health Utility Index (HUI Mark-2 and Mark-3)] were administered prospectively. Additional clinical and laboratory data and normative data for healthy individuals, were available. ANALYSIS: Scores were compared using analysis of variance and multiple regression. RESULTS: One hundred and forty-six patients with CH-B, CH-C and PBC were included [mean age 47.1 years (+/ 11.6), 41% female, 33% cirrhosis]. CH-C and PBC patients scored the lowest on all CLDQ, SF-36 and HUI domains compared with CH-B patients and healthy controls. CH B patients had scores similar to the healthy population, measured by most CLDQ and SF-36 scales. However, the HUI scores for CH-B patients showed more impairment than population norms. Having CH-B and not having cirrhosis were predictive of utility and HRQL scores in multivariate models. CONCLUSIONS: CH-B patients have better HRQL than CH-C, PBC and population norms. CH-B patients' overall utility scores are lower than population norms. PMID- 17845542 TI - Evolution of hepatitis C virus non-structural 5A gene in the progression of liver disease to hepatocellular carcinoma. AB - BACKGROUND: The interaction between the hepatitis C virus (HCV) non-structural 5A (NS5A) protein of HCV and the protein kinase R (PKR), which is an effector of the cellular antiviral response and has been defined as a tumour suppressor, may affect the control of protein synthesis and cell growth. AIM: We investigated the genetic evolution of the NS5A region in the NS5A PKR-binding domain (NS5A-PKRbd) of patients with HCV 1b-related cirrhosis who subsequently developed or not hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The quasispecies composition of NS5A-PKRbd was inferred by sequencing an average of 15 clones per sample in specimens obtained from 26 patients with cirrhosis who developed or not HCC during a follow-up of 5 years. RESULTS: At baseline, 13/17 patients with final HCC and six out of nine patients with cirrhosis who subsequently did not develop HCC harboured a wild-type (wt) strain master sequence. Over time, the prevalence of wt strain was higher in patients who developed HCC with respect to those who maintained the cirrhosis status (15/17 vs 4/9, respectively; P=0.0166). CONCLUSION: The maintenance of or evolution to the wt strain of the NS5A domain in cirrhotic patients with final HCC highlights the central role of NS5A protein in the viral life cycle and in the progression of liver disease. PMID- 17845543 TI - Influence of IL-10RA and IL-22 polymorphisms on outcome of hepatitis C virus infection. AB - BACKGROUND: Two receptor chains, IL-10RA and IL-10RB, are known to mediate the functions of interleukin-10 (IL-10), which has been shown to be involved in the progression of persistent hepatitis C virus (HCV) infection. Little information is available on the role of host genetic variation in IL-10 receptor genes and outcome of HCV infection. IL-22, an IL-10 homologue, shares the IL-10RB receptor chain with IL-10 and has antiviral properties. We investigated the possible role of polymorphisms in the IL-10RA and IL-22 genes in hepatitis C disease pathogenesis. METHODS: This study population consisted of 631 HCV patients, recruited from several hepatology clinics across Europe. We genotyped four single nucleotide polymorphisms (SNPs) in the IL-10RA and six SNPs in the IL-22 gene by ligation detection reaction or restriction fragment length polymorphism. Outcome of HCV infection was assessed according to viral clearance, treatment response, severity of fibrosis and overall inflammation. CONCLUSIONS: Variation in IL-10RA appeared to be correlated with response to treatment and inflammation. Two SNPs in IL-22 affected treatment response and viral clearance respectively. We furthermore report on allele and haplotype frequencies and linkage disequilibrium for IL-10RA and IL-22. Our results indicate that genetic variation in these genes may play a modulatory role in the outcome of hepatitis C infection. PMID- 17845544 TI - Suspected cross-hepatotoxicity of flutamide and cyproterone acetate. AB - Flutamide and cyproterone acetate (CPA) are both oral anti-androgens commonly used to treat advanced prostatic cancer. We report a case of drug-induced hepatotoxicity after consecutive treatment with flutamide and CPA. A 78-year-old male with advanced prostatic adenocarcinoma had been treated with flutamide 750 mg/day p.o. and leuproleride acetate 22.5 mg/3 months i.m. Three months later, the patient complained of choluria and jaundice. Laboratory examination revealed severe hepatocellular insufficiency. Flutamide-induced hepatotoxicity was suspected and therefore flutamide was withdrawn. His liver function abnormalities resolved after drug discontinuation. He was subsequently started on CPA 150 mg/day and again developed hepatotoxicity with severe hepatocellular impairment, which completely recovered after drug discontinuation. Other causes of acute liver failure were appropriately ruled out in both episodes and there was no evidence of active prostate cancer or liver metastases in both episodes. The occurrence of hepatotoxicity associated with flutamide and CPA on separated occasions suggests the possibility of a common mechanism of injury. It may become necessary to reassess the common practice of switching to another anti-androgen when hepatotoxicity appears. A closer monitoring of liver enzymes might be necessary in such cases, as an increased risk of a new severe hepatotoxicity event cannot be ruled out. PMID- 17845545 TI - Fulminant liver failure secondary to haemorrhagic dengue in an international traveller. AB - Dengue infections are caused by a single-stranded RNA virus, which has four serotypes (DEN 1-4); mosquitoes of the genus Aedes serve as vectors of transmission. Risk factors for dengue infection are related to both the host and virus. Age, gender, immune status, and genetic background of the host all contribute to the severity of dengue infection. Recently, international travel to endemic areas has also been identified as a major risk factor for both primary and secondary dengue infection. Dengue remains a diagnostic challenge, given its protean nature, ranging from mild febrile illness to profound shock. The most severe manifestation of dengue infection is dengue shock syndrome, which has an estimated mortality rate close to 50%. Dengue shock syndrome typically presents with increased anion gap metabolic acidosis, disseminated intravascular coagulation, severe hypotension, and jaundice. Liver involvement appears to occur more frequently when infections involve DEN-3 and DEN-4 serotypes. While hepatocellular damage has been reported previously in dengue infection, acute liver failure is an extremely rare occurrence in adults. We report a patient with dengue shock syndrome who presented with acute liver failure and hepatic encephalopathy after recent travel to an endemic area. PMID- 17845548 TI - Twice as much to be half as good: the undervaluing of mental health nursing leadership in academia. PMID- 17845546 TI - Rimonabant as a novel therapeutic option for nonalcoholic steatohepatitis. PMID- 17845549 TI - Rural men and mental health: their experiences and how they managed. AB - There is a growing awareness that a primary source of information about mental health lies with the consumers. This paper reports on a study that interviewed rural men with the aim of exploring their mental health experiences within a rural environment. The results of the interviews are a number of stories of resilience and survival that highlight not only the importance of exploring the individuals' perspective of their issues, but also of acknowledging and drawing on their inner strengths. Rural men face a number of challenges that not only increase the risk of mental illness but also decrease the likelihood of them seeking and/or finding professional support. These men's stories, while different from each other, have a common thread of coping. Despite some support from family and friends, participants also acknowledged that seeking out professional support could have made the recovery phase easier. Mental health nurses need to be aware, not only of the barrier to professional support but also of the significant resilience that individuals have and how it can be used. PMID- 17845550 TI - Next of kin's conceptions of the quality of care in the psychiatric setting: a phenomenographic study. AB - The next of kin play a decisive role in the care provided for patients. This and their unique experience of psychiatric care make it important to include them when defining quality of care. The aim of the present study was to describe how next of kin perceive the concept of quality of care in the case of psychiatric care. Twelve next of kin were included in a qualitative interview study and a phenomenographic approach was used for the analysis of the interviews. The next of kin described quality of care mainly from their own perspective but also to a large extent from the patient's perspective as well. Five descriptive categories resulted: dignity, security, participation, recovery, and health-promoting surroundings. Good relations and communication between staff, patients, and next of kin emerged as the central factors regarding the quality of psychiatric care. The next of kin asked for information about psychiatric illnesses and wanted to cooperate in the care. They avoid telling others about their family member's psychiatric illness because of a feeling of shame and guilt. Staff education regarding such feelings and stigmatization could be useful in furthering the understanding of the next of kin's distress and developing interventions to alleviate it. Clinical practice can be improved by guidelines and instruments developed on the basis of this study. PMID- 17845551 TI - Exploration of therapeutic interventions that accompany the administration of p.r.n. ('as required') psychotropic medication within acute mental health settings: a retrospective study. AB - Within acute mental health settings, pro re nata (p.r.n.) 'as required' medication is a widely used adjunct to regular treatment plans, and is administered at the discretion of a registered nurse. However, there is concern that some orders may benefit staff more than patients by providing a 'quick fix' to compensate for inadequate therapeutic programmes. Previous authors assert that p.r.n. medication administration should not be the first line of action, but should be used when other less invasive interventions such as de-escalation, talking, or separation from the group are unsuccessful. This project explored the occurrence of p.r.n. medication administration and the type of alternative therapeutic interventions that are documented as accompanying its administration. A retrospective 1-month chart audit was undertaken for a cohort of inpatients in a 20-bed mental health facility attached to a regional hospital in New South Wales, Australia. Forty-seven patients (73.4%) received p.r.n. medication at least once, with a total of 309 doses of p.r.n. medication administered during this time. There were wide variations in the documented rationales, and for nearly three-quarters (73%) of p.r.n. medication administrations, no other therapeutic intervention was documented as occurring prior to administration. PMID- 17845552 TI - Who cares for older people with mental illness? A survey of residential aged care facilities in the Australian Capital Territory: implications for mental health nursing. AB - Residential aged care facilities are increasingly becoming locations wherein the most frail and older people with mental illness live out the remainder of their lives, yet it has become apparent in recent years that these institutions are fraught with a variety of social and clinical problems. One issue of concern has been the exodus of registered nurses (both general and psychiatric), who have been increasingly replaced by carers with little or no expertise in psychiatric illness or disorders of cognitive decline. This 'de-professionalizing' of aged care has important implications for the well-being of clients, particularity those with complex mental health problems. In this survey we sought to discover demographic information concerning those who provide front-line care to this population of aged Australians, and we sought also to ascertain how much education in caring for residents who suffer specifically from neurodegenerative disorders (the dementias) and mental illness was provided by the facilities to those who care for such older people. The lack of training in the areas of mental health and cognitive impairment raises a variety of issues that mental health nurses need to address. These issues cover clinical, professional, and social justice dimensions. We believe that mental health nurses are strategically and professionally placed to take a leadership role in raising the profile of aged care in this country and they need to act proactively to secure the well-being of this particularly vulnerable client group. PMID- 17845553 TI - Ogres and Angels in the madhouse. Mental health nursing identities in film. AB - This project applied ethnographic content analysis to examine 19 American films made during the period 1942-2005. The purpose of this examination is to consider how the medium of American film portrays psychiatric mental health nursing and its world within the hospital. It critiques the way film frames mental health nursing and the profession's interactions with other disciplines, such as psychiatry, that might reveal a disposition that is peculiar to this group. It concludes that Hollywood film genre continues to perpetuate the notion that mental health nursing occupies an aberrant, secret, and dangerous world and that its role remains one of custodial companionship. If Chiari, Pinel, and Tuke, the founders of moral therapy during the Age of Reason observed these films, they could be forgiven if they wondered whether psychiatric mental nursing remained trapped in the Middle Ages While some of the films reviewed may be considered vacuous nonsense, its discourses reflect how society views people with serious mental illness and those who nurse them. This critique is a challenge for the profession to educate society regarding the profession's true work, reclaiming its commitment to affirming the dignity and human rights of those with mental illness by instigating political strategies that will destabilize the subversive and dividing practices that film merely manipulates. PMID- 17845555 TI - Consumer-clinician co-taught borderline personality disorder training: a pilot evaluation. AB - This paper describes a consumer-clinician co-taught borderline personality disorder training programme for clinicians, of whom the largest group were nurses, working in mental health and substance use fields. A pilot evaluation of 73 participants attending the training rated the training as superior to evaluations of an earlier clinician-only-taught training. This study of a novel co-taught training programme found that the consumer input added substantial value. Findings indicate that consumer input into education programmes can make a significant positive contribution to the delivery of mental health services training with likely impacts on mental health service delivery. The potential importance of the findings warrants a comprehensive multicentre study. Confirming the findings would have implications for future borderline personality disorder training programmes. PMID- 17845554 TI - Suicide risk and protective factors among youth experiencing school difficulties. AB - Youth who experience difficulty in school are at risk for suicide, yet there is little published information specific to risk and protective factors among this group. The purpose of this study was to conduct an in-depth examination of risk and protective factors associated with suicidal behaviour among youth who were experiencing problems in school and to compare these factors between suicide risk and non-suicide risk subgroups. Participants were 730 high school students in the Northwest and Southwest regions of the United States, aged 14-21 years. All participants were known to be experiencing difficulty with grades and/or attendance. Students completed a paper-and-pencil questionnaire and a one-on-one interview, which assessed suicidal behaviours as well as risk factors (e.g. drug involvement, emotional distress, stress), and protective factors (e.g. self esteem, coping, support). Analysis of covariance tests, controlling for age and sex, were conducted to examine differences between the suicide risk and non suicide risk groups on each risk and protective factor. The suicide risk subgroup reported higher levels of all risk factors, except alcohol and marijuana use, and lower levels of protective factors. While the groups did not differ on frequency of alcohol or marijuana use, they did differ on other illicit drug use and consequences of alcohol and other illicit drug use. Recommendations for nurses practising in school settings are discussed. PMID- 17845556 TI - Mental health nursing research: the contemporary context. AB - While the need to develop and conduct research has been prominent in mental health nursing for some time, the current funding climate in tertiary institutions has created even more pressure for research outputs. The Research Assessment Exercise is well ingrained in UK institutions, New Zealand is about to enter the second round of the Performance-based Research Funding model, and Australia is committed to a Research Quality Framework. There is much to learn from nursing departments in those countries that have already been part of the process. This paper will present a content analysis of what mental health nursing research is currently being published in nursing journals and discuss the implications of the research assessment exercises on its future. Those mental health nursing articles sampled in the study revealed a shift beginning towards more consumer-focused research was occurring but that there was a need for more research into the effectiveness of specific mental health nursing interventions. Most of the articles also reported on small-scale research. It concludes that research needs to be more clinically orientated and less profession-orientated. It also suggests a need to focus on larger-scale studies possibly situated within a collaborative research programme. These programmes need to be more collaborative both cross-institutional and cross-disciplinary. PMID- 17845557 TI - The islet transplant experiment: time for a reassessment. PMID- 17845558 TI - Variable evaluation and selection criteria for living kidney donors: have we gotten the message yet? PMID- 17845559 TI - Expression patterns of regulatory T-cell markers in accepted and rejected nonhuman primate kidney allografts. AB - The identification of FOXP3 expressing cells in recipients of an allograft, in particular inside the graft itself, may help to define criteria for immunosuppressive drug withdrawal. We therefore examined expression patterns of several regulatory T-cell (Treg) markers in kidney biopsies and kidney tissues taken at the time of graft rejection from monkeys treated with alpha CD40, alpha CD86, CsA, a combination of these or after drug withdrawal. In advanced stages of rejection, organized multifocal nodular infiltrates, with mature dendritic cells, T cells and B cells could be found. In contrast, interstitial infiltrates contain more macrophages, less T cells and few B cells. Cells expressing FOXP3, CD25 and CTLA-4 were mainly found in nodular infiltrates of rejected tissue samples. A significant correlation was found between the percentage FOXP3(+) cells and markers for rejection, i.e. creatinine levels and Banff interstitial and tubular infiltrate scores. The type of immunosuppression did not influence the percentage of cells expressing Treg markers. Three animals with prolonged drug-free survival showed low numbers of FOXP3(+) cells. We conclude that the presence of intragraft FOXP3(+) cells is not confined to tolerated grafts, but should be considered as part of the normal immune response during rejection. PMID- 17845560 TI - A synthetic mechano growth factor E Peptide enhances myogenic precursor cell transplantation success. AB - Myogenic precursor cell (MPC) transplantation is a good strategy to introduce dystrophin expression in muscles of Duchenne muscular dystrophy (DMD) patients. Insulin-like growth factor (IGF-1) promotes MPC activities, such as survival, proliferation, migration and differentiation, which could enhance the success of their transplantation. Alternative splicing of the IGF-1 mRNA produces different muscle isoforms. The mechano growth factor (MGF) is an isoform, especially expressed after a mechanical stress. A 24 amino acids peptide corresponding to the C-terminal part of the MGF E domain (MGF-Ct24E peptide) was synthesized. This peptide had been shown to enhance the proliferation and delay the terminal differentiation of C(2)C(12) myoblasts. The present study showed that the MGF Ct24E peptide improved human MPC transplantation by modulating their proliferation and differentiation. Indeed, intramuscular or systemic delivery of this synthetic peptide significantly promoted engraftment of human MPCs in mice. In vitro experiments demonstrated that the MGF-Ct24E peptide enhanced MPC proliferation by a different mechanism than the binding to the IGF-1 receptor. Moreover, MGF-Ct24E peptide delayed human MPC differentiation while having no outcome on survival. Those combined effects are probably responsible for the enhanced transplantation success. Thus, the MGF-Ct24E peptide is an interesting agent to increase MPC transplantation success in DMD patients. PMID- 17845561 TI - Engraftment of adult porcine islet xenografts in diabetic nonhuman primates through targeting of costimulation pathways. AB - Recent advances in human allogeneic islet transplantation have established beta cell replacement therapy as a potentially viable treatment option for individuals afflicted with Type 1 diabetes. Two recent successes, one involving neonatal porcine islet xenografts transplanted into diabetic rhesus macaques treated with a costimulation blockade-based regimen and the other involving diabetic cynomolgus monkeys transplanted with adult porcine islet xenografts treated with an alternative multidrug immunosuppressive regimen have demonstrated the feasibility of porcine islet xenotransplantation in nonhuman primate models. In the current study, we assessed whether transplantation of adult porcine islet xenografts into pancreatectomized macaques, under the cover of a costimulation blockade-based immunosuppressive regimen (CD28 and CD154 blockade), could correct hyperglycemia. Our findings suggest that the adult porcine islets transplanted into rhesus macaques receiving a costimulation blockade-based regimen are not uniformly subject to hyperacute rejection, can engraft (2/5 recipients), and have the potential to provide sustained normoglycemia. These results provide further evidence to suggest that porcine islet xenotransplantation may be an attainable strategy to alleviate the islet supply crisis that is one of the principal obstacles to large-scale application of islet replacement therapy in the treatment of Type 1 diabetes. PMID- 17845562 TI - Allopeptide-specific CD4(+) T cells facilitate the differentiation of directly alloreactive graft-infiltrating CD8(+) T Cells. AB - To investigate the mechanism of CD4(+) T-cell help during the activation and differentiation of directly alloreactive CD8(+) T cells, we examined the development of obliterative airways disease (OAD) following transplantation of airways into fully mismatched recipient mice deficient in CD4(+) T cells. BALB/c trachea allografts became fibrosed significantly less frequently in B6 CD4(-/-) recipients as compared to wildtype controls. Furthermore, class I-directed cytotoxicity failed to develop in the absence of CD4(+) T cells. The infiltration of graft tissue by primed L(d)-specific directly alloreactive 2C CD8(+) T cells was not found to depend on the presence of CD4(+) T cells. Nevertheless, graft infiltrating 2C CD8(+) T cells failed to express CD69 and granzyme B when CD4(+) T-cell help was unavailable. Importantly, reconstitution of B6 CD4(-/-) recipient mice with graft peptide-specific TCR-Tg CD4(+) T cells (OT-II or TEa) capable of recognizing antigen only on recipient APC allowed for full expression of CD69 and granzyme B by the directly alloreactive CD8(+) T cells and restored the capacity of recipients to reject their allografts. These results demonstrate that indirectly alloreactive CD4(+) T cells ensure the optimal activation and differentiation of graft-infiltrating directly alloreactive CD8(+) T cells independent of donor APC recognition. PMID- 17845563 TI - IFN-gamma prevents early perforin-granzyme-mediated destruction of kidney allografts by inducing donor class I products in the kidney. AB - Interferon-gamma (Ifng) protects organ allografts: mouse kidney allografts lacking Ifng receptors rapidly fail with massive ischemic necrosis around days 5 to 7, reflecting microcirculation failure. We hypothesized that Ifng protects the graft by preventing perforin-granzyme-mediated cytotoxic damage to the microcirculation by inducing class Ia and/or Ib products. We transplanted kidney allografts lacking Ifng receptors into various knockout hosts. The necrosis/congestion phenotype did not require host B cells or IL-4 and IL-13 receptors, but required the T-cell alloresponse: it did not occur if the hosts were syngeneic or T-cell deficient. However, host perforin-granzyme mechanisms were required: no necrosis developed if hosts lacked either perforin or granzymes A and B. The ability of Ifng to protect the allograft required donor class I products: allografts lacking class I products due to Tap1 or beta2 microglobulin deficiency developed a similar necrosis-congestion phenotype at day 7 despite Ifng receptors being present. Thus when host cytotoxic T cells infiltrate organ allografts, Ifng prevents their perforin-granzyme mechanism from compromising the microcirculation by a mechanism requiring donor class Ia or Ib products. We propose that donor class Ia or Ib products are needed to trigger inhibitory receptors on effector T cells. PMID- 17845564 TI - High risk of sensitization after failed islet transplantation. AB - Human Leukocyte Antigen (HLA) antibodies posttransplant have been associated with an increased risk of early graft failure in kidney transplants. Whether this also applies to islet transplantation is not clear. To achieve insulin independence after islet transplants multiple donor infusions may be required. Hence, islet transplant recipients are at risk of sensitization after transplantation. Islet transplant recipients were screened for HLA antibodies posttransplant by flow based methods. A total of 98 patients were studied. Twenty-nine patients (31%) developed de novo donor specific antibodies (DSA) posttransplant. Twenty-three patients developed DSA while on immunosuppression (IS). Among recipients who have discontinued IS, 10/14 (71%) are broadly sensitized with panel reactive antibody (PRA) >or=50%. The risk of becoming broadly sensitized after transplant was 11/69 (16%) if the recipient was unsensitized prior to transplant. The majority of these antibodies have persisted over time. Appearance of HLA antibodies posttransplant is concerning, and the incidence rises abruptly in subjects weaned completely from IS. This may negatively impact the ability of these individuals to undergo further islet, pancreas or kidney transplantation and should be discussed upfront during evaluation of candidates for islet transplantation. PMID- 17845565 TI - Human islets derived from donors after cardiac death are fully biofunctional. AB - Islets from brain-dead donors (BDDs) are being used in the treatment of Type 1 diabetes. However, both donor numbers and islet survival are limited. We explored the clinical potential for islets from non-heart-beating donors (NHBDs), who have lower circulating cytokines, by comparing islets from 10 NHBDs against 12 identically-isolated islets from BDDs over the same time period. The quantity and quality of islets from NHBDs was good. NHBD yielded approximately 12.6% more islets than those of BDDs (505,000 +/- 84,230 vs. 400,970 +/- 172,430 islet equivalent number [IEQ]/pancreas, p = 0.01) with comparable viability. ATP and GTP contents were lower (6.026 +/- 3.076 vs. 18.105 +/- 7.8 nM/mg protein, p = 0.01 and 1.52 +/- 0.87 vs. 3.378 +/- 0.83 nM/mg protein, p = 0.04) and correlated negatively to warm ischemia time (R(2)= 0.8022 and R(2)= 0.7996, respectively). Islets from NHBDs took longer to control hyperglycemia in diabetic mice, but were equally able to sustain euglycemia. With a warm ischemia time (WIT) of or=3 was 3.5%. Center living-donor volume (OR = 0.97, 95% CI = 0.95-0.99) and the ratio of living-donors to all donors (living and deceased) (OR = 0.94, 95% CI = 0.92-0.96) were associated with a lower risk of all complications. Donor age >50 years (OR = 4.25, 95% CI = 1.22-14.87) was associated with a higher risk of major complications. Living liver donation is currently performed with a low risk of major morbidity. Use of administrative data represents an important tool to facilitate a better understanding of donor risk factors. PMID- 17845569 TI - Renin angiotensin system blockade in kidney transplantation: a systematic review of the evidence. AB - ACE-inhibitors and angiotensin receptor blockers (ARB) slow the progression of renal disease in non-transplant patients. A systematic review of randomized trials (n = 21 trials with 1549 patients) was conducted to determine the effect of ACE-inhibitor or ARB use following kidney transplantation. With a median follow-up of 27 months, ACE-inhibitor or ARB use was associated with a significant decrease in glomerular filtration rate (-5.8 mL/min; 95% CI -10.6 to 0.99). ACE-inhibitor or ARB use resulted in a lower hematocrit (-3.5%; 95% CI 6.1 to -0.95), reduction in proteinuria (-0.47 gm/d; 95% CI -0.86 to -0.08) but no change in the serum potassium (0.18 mmol/L; 95% CI -0.03 to 0.40). ACE inhibitor or ARB use results in clinically important reductions in proteinuria, hematocrit and glomerular filtration rate in renal transplant recipients, but there are insufficient data to determine the effect on patient or graft survival. Randomized trials of sufficient power and duration that examine these hard outcomes should be conducted. Until such trials are completed, this study provides quantitative estimates of the risks and benefits of ACE-inhibitor or ARB use that can be used by clinicians considering prescribing these medications to kidney transplant recipients or to researchers designing future trials. PMID- 17845570 TI - Expanding kidney paired donation through participation by compatible pairs. AB - In kidney paired donation (KPD), incompatible pairs exchange kidneys so that each recipient receives a compatible organ. This modality is underutilized partly because of the difficulty of finding a suitable match among incompatible pairs. Alternatively, recipients with compatible donors might enter KPD arrangements in order to be matched with a donor predicted to give greater allograft durability or for other altruistic reasons. Using simulated donors and recipients, we investigated the impact of allowing recipients and their compatible donors to participate in KPD. For KPD programs of any size, the participation of compatible donor/recipient pairs nearly doubled the match rate for incompatible pairs (28.2% to 64.5% for single-center program, 37.4% to 75.4% for national program). Legal, logistical, and governmental controversies have hampered the expansion of KPD in the United States by delaying the creation of a national program. The inclusion of compatible pairs into small single-center pools could achieve match rates that would surpass that which could be realized by a national list made up of only incompatible pairs. This new paradigm of KPD can immediately be instituted at the single-center level, while the greatest gains will be achieved by incorporating compatible pairs into a national program. PMID- 17845571 TI - Renal transplantation in patients with pre-transplant donor-specific antibodies and negative flow cytometry crossmatches. AB - The clinical significance of pre-transplant donor-specific antibodies (DSA), despite negative cytotoxicity and flow cytometry crossmatches (FCXMs), is unknown. We performed a retrospective cohort study of 60 living donor renal transplant recipients, all with pre-transplant cytotoxicity and T-cell and B-cell FCXMs that were negative. Twenty recipients had pre-transplant DSA detected by enzyme-linked immunosorbent assays (ELISA) and/or microbead methods. Forty contemporaneous DSA-negative controls were selected. In the DSA-positive group, after a median follow-up of 8.2 months (25-75% range, 5.4-22.8 months), patient survival was 100% and allograft survival was 95.0%. Acute humoral rejection (AHR) developed in four patients (20.0%). Three of the AHR episodes occurred within the first month post-transplant. Median serum creatinine at last follow-up was 1.3 mg/dL (25-75% range, 1.0-1.6 mg/dL), versus 1.1 mg/dL (25-75% range, 0.9-1.4 mg/dL) in the DSA-negative controls (p = 0.29). Only one of the 40 controls developed AHR (2.5%). Pre-transplant DSA was associated with a significantly increased incidence of AHR (p = 0.02 by log-rank test). In conclusion, despite negative pre-transplant cytotoxicity and FCXMs, renal transplant recipients with pre-transplant DSA detected by solid-phase methods may have an increased incidence of AHR and require close monitoring post-transplant. PMID- 17845572 TI - Outcome in cardiac recipients of donor hearts with increased left ventricular wall thickness. AB - The ongoing shortage of donors for cardiac transplantation has led to a trend toward acceptance of donor hearts with some structural abnormalities including left ventricular hypertrophy. To evaluate the outcome in recipients of donor hearts with increased left ventricular wall thickness (LVWT), we retrospectively analyzed data for 157 cardiac donors and respective recipients from January 2001 to December 2004. There were 47 recipients of donor heart with increased LVWT >or=1.2 cm, which constituted the study group and 110 recipients of a donor heart with normal LVWT < 1.2 cm that formed the control group. At 3 +/- 1.5 years, recipient survival was lower (50% vs. 82%, p = 0.0053) and incidence of allograft vasculopathy was higher (50% vs. 22%, p = 0.05) in recipients of donor heart with LVWT > 1.4 cm as compared to LVWT 1.4 cm (p = 0.003), recipient preoperative ventricular assist device (VAD) support (p = 0.04) and bypass time > 150 min (p = 0.05) were predictors of reduced survival. Our results suggest careful consideration of donor hearts with echocardiographic evidence of increased LVWT in the absence of hypovolemia, because they may be associated with poorer outcomes; such hearts should potentially be reserved only for the most desperately ill recipients. PMID- 17845573 TI - Expression profiling of human donor lungs to understand primary graft dysfunction after lung transplantation. AB - Lung transplantation is the treatment of choice for end-stage pulmonary diseases. A limited donor supply has resulted in 4,000 patients on the waiting list. Currently, 10-20% of donor organs offered for transplantation are deemed suitable under the selection criteria, of which 15-25% fail due to primary graft dysfunction (PGD). This has spawned efforts to re-examine the current selection criteria as well as search for alternative donor lungs selection criteria. In this study, we attempt to further our understanding of PGD by observing the changes in gene expression across donor lungs that developed PGD versus those that did not. From our analysis, we have obtained differentially expressed transcripts that were involved in signaling, apoptosis and stress-activated pathways. Results also indicate that metallothionein 3 was over expressed in lungs that didn't develop PGD. This is the first such attempt to perform expression profiling of actual human lungs used for transplantation, for the identification of a molecular signature for PGD. PMID- 17845574 TI - Association between waiting times for kidney transplantation and rates of live donation. AB - A deceased donor (DD) allocation system incorporating net life survival benefit has been proposed. In this system, many kidneys will be shifted to younger recipients, thereby decreasing their waiting times. The goal of this study was to determine the potential effects of altering waiting times on the likelihood of live donor kidney transplantation (LDKT). We analyzed 93,727 waiting list candidates to determine the association of various patient factors with likelihood of LDKT. The proportion of patients receiving LDKT was compared by the median DD waiting time at that patient's transplant center for someone of that patient's age category and race. LDKT was consistently higher as waiting times became longer. After adjusting for all other factors associated with likelihood of LDKT, waiting time remained a significant, independent predictor. Patients with the longest DD waiting times had 2.3-fold higher odds of LDKT (95% CI 2.11 2.58, p < 0.001). In planning the new DD allocation policy, we must account for resulting alterations in LDKT. It is possible that shifting DD kidneys to younger recipients may decrease LDKT or shift it to older recipients, net effects not consistent with the goal of net life survival benefit. PMID- 17845575 TI - Sirolimus-associated infertility: case report and literature review of possible mechanisms. AB - The mammalian-target-of-rapamycin/mTOR-inhibitor sirolimus as a component of the immunosuppressive strategy after solid organ transplantation is effective at preventing allograft rejection. However, recent reports indicate that sirolimus is associated with altered sex hormone levels and impaired sperm quality parameters. Herein, we report on a case of sirolimus-associated infertility in a young male heart-lung transplant recipient and provide a detailed synopsis of potential mechanisms by which sirolimus may negatively influence spermatogenesis. Testicular immunohistochemistry, the course of sex hormone and sperm quality parameters of our patient support the hypothesis that mTOR might act as an important key regulator in the reproductive system. Fortunately, due to withdrawal of sirolimus as part of the maintenance, immunosuppression improved sperm quality and sex hormone parameters could be observed. Recently, these improvements even resulted in a spontaneous pregnancy of the patient's wife more than 1 year after the drug was withdrawn. In our view, oligospermia as a possible and at least partly reversible side-effect of mTOR inhibitors has to be taken into consideration, particularly, when administrated to young male patients. PMID- 17845576 TI - Pancreas graft salvage using pancreatico-duodenectomy with enteric drainage. AB - As demand for donor pancreases increases, attempts are being made to utilize even marginal grafts for transplantation. Injury during pancreas recovery can predispose to posttransplant complications and graft loss. Early recognition and correction can salvage these grafts. The authors report an instance of poor segmental perfusion of the pancreas graft that was salvaged by pancreas head resection and enteric drainage through a Roux-en-Y pancreatico-jejunostomy. PMID- 17845577 TI - Combined double lung-liver transplantation for cystic fibrosis without cardio pulmonary by-pass. AB - Sequential bilateral single lung-liver transplantation (SBSL-LTx) is a therapeutic option for patients with end stage lung and liver disease (ESLLD) due to cystic fibrosis (CF). A few cases have been reported, all of them were performed with the use of cardio-pulmonary by-pass (CPB). We performed SBSL-LTx in three young men affected by CF. All the recipients had respiratory failure and portal hypertension with hypersplenism. Along with lung transplants, two patients received a whole liver graft and one an extended right graft from an in situ split liver. During transplantation neither CPB nor veno-venous by-pass (VVB) were employed. Immunosuppression was based on basiliximab, tacrolimus, steroids and azathioprine. The three recipients are alive with a median follow-up of 670 days (range 244-1,533). Combined SBSL-LTx is a complex but effective procedure for the treatment of ESLLD due to CF, not necessarily requiring the use of CPB or VVB. PMID- 17845579 TI - The allergen bronchoprovocation model: an important tool for the investigation of new asthma anti-inflammatory therapies. AB - Allergen bronchoprovocation tests have been used for more than two decades in the investigation of respiratory allergic diseases such as asthma and rhinitis. These bronchial challenges are now well standardized and can offer key information on the therapeutic potential of new agents and on their anti-inflammatory effects on the airways. Both standard and low-dose allergen provocations are safe when performed by experienced investigators and do not lead to persistent worsening of asthma or change in airway function. The evaluation of new therapeutic agents by these methods can also provide important information on the mechanisms of development and persistence of airway diseases. PMID- 17845580 TI - The polymorphisms of Eotaxin 1 and CCR3 genes influence on serum IgE, Eotaxin levels and mild asthmatic children in Taiwan. AB - BACKGROUND: Asthma is a complex disorder, which is known to be affected by interactions between genetic and environmental factors. The human Eotaxin 1 and CCR3 attract eosinophils and Th2-lymphocytes to migrate to the inflammatory foci that could represent a key mechanism in allergy and asthma. OBJECTIVE: We hypothesized that Eotaxin1 gene Ala23Thr and A-384 G, and CCR3 gene T51C polymorphisms are associated with plasma Eotaxin levels and predispose individuals to asthma pathogenesis. METHODS: One hundred seventy-eight hospital based asthmatic children and 277 community-based controls aged from 5 to 12 years were recruited in southern Taiwan. Whole blood samples and questionnaires were collected. In this study, we addressed genetic effects of Eotaxin 1 and CCR3 genes on asthma, plasma IgE and Eotaxin 1 levels. RESULTS: In comparison with subjects with Ala23Ala genotype, Ala23Thr polymorphism of the Eotaxin 1 gene showed a significant protective effect on asthma (AOR = 0.58, 95% CI = 0.37 0.92). We demonstrated that the mean Eotaxin 1 concentration was significantly higher in subjects with Ala23Ala than in subjects with Thr23Thr (P = 0.005) or Ala23Thr (P = 0.07), which showed a gene-dose dependent relationship. But, we observed that the A-384G polymorphism of Eotaxin 1 gene and T51C polymorphism of CCR3 gene are not associated with asthma. CONCLUSION: This study finding provide a strong evidence that Eotaxin 1 Thr23Thr homozygote has a protective effect on asthma and significantly decreases plasma Eotaxin 1 concentrations in asthmatics in Taiwan. PMID- 17845581 TI - Eosinophilic inflammation: mechanisms regulating IL-5 transcription in human T lymphocytes. AB - BACKGROUND: Interleukin (IL)-5 is a key regulator of eosinophilia in allergic inflammation and parasite infections but the mechanisms regulating IL-5 expression in activated human T lymphocytes are poorly understood. From studies on mouse cells, the activation protein (AP)-1 and GATA-3 sites in the proximal promoter region appear to be important in IL-5 regulation but the significance of an adjacent Ets/nuclear factor of activated T cell (NFAT) site has been less clear. METHODS: Interleukin-5 transcriptional activity was measured by transfection of reporter genes into the human HSB-2 cells and normal T lymphocytes. Expression vectors encoding transcription factors were used for transactivation studies and IL-5 expression measured using reporter genes and mRNA levels. Transcription factor binding was shown with chromatin immunoprecipitation (ChIP). RESULTS: HSB-2 cells showed high inducible expression of IL-5 mRNA. Mutation of reporter gene plasmids showed the Ets/NFAT site was of equal importance to the AP-1 and GATA-3 sites in regulating IL-5 transcription. Transactivation by Ets1 increased luciferase expression 15-fold, in the absence of stimulation, and AP-1 (c-Fos/c-Jun) and GATA-3 gave transactivations of 85 fold, and 100-fold, respectively. Synergistic interactions were demonstrated between Ets1, GATA-3 and AP-1. Dominant-negative AP-1 inhibited IL-5 transcription. Transactivation by GATA-3 and synergy between GATA-3, Ets1 and AP 1 were verified measuring IL-5 mRNA levels. Chromatin immunoprecipitation showed increased binding of Ets1 and GATA-3 to the IL-5 promoter after stimulation. The importance of the Ets1 site and of synergistic interactions between the three transcription factors were verified with primary human T cells. CONCLUSION: Ets1, GATA-3 and AP-1 synergize to regulate IL-5 transcription in human T cells. PMID- 17845582 TI - Circulating myeloid and plasmacytoid dendritic cells after allergen inhalation in asthmatic subjects. AB - BACKGROUND: Dendritic cells are key contributors to initiation and maintenance of T-cell immunity to inhaled allergen. The purpose of this study was to enumerate the changes in peripheral blood myeloid (mDCs) and plasmacytoid dendritic cells (pDCs), the DCs expressing chemokine receptor 6 (CCR6) and chemokine receptor 7 (CCR7), following diluent and allergen inhalation in asthmatic subjects. METHODS: Peripheral blood was obtained from 16 allergic asthmatic subjects before and at 0.5, 1, 2, 3, 4, 6, 24, and 48 h after inhaled diluent and allergen challenges. Dendritic cells were enumerated using flow cytometry. RESULTS: Allergen inhalation significantly reduced mDCs at 6 h (21.3 +/- 2.0 vs 15.0 +/- 1.8/microl blood; P < 0.05) and 24 h (21.5 +/- 3.4 vs 16.4 +/- 2.4/microl blood; P < 0.05) after challenge. Circulating pDCs were significantly lower than baseline up to 24 h after both allergen and diluent challenges. There was a significant efflux of CCR6(+) mDCs from peripheral blood at 6 h and CCR6(+) pDCs at 4 h after allergen challenge, when compared with diluent. There was no difference in the number of circulating CCR7(+) mDCs or pDCs after diluent or allergen challenges. CONCLUSIONS: Peripheral blood mDCs and CCR6(+) mDCs, but not pDCs, are reduced up to 24 h after allergen inhalation. Thus, allergen inhalation causes trafficking of immature CCR6(+) DCs from blood into the airway, while that of the trafficking of the mature CCR7(+) DCs from the airways into the regional lymph nodes probably occurs through the lymphatic system. PMID- 17845583 TI - Asthma definitions, relative validity and impact on known risk factors in young Brazilians. AB - BACKGROUND: An asthma score was proposed in the European Community Respiratory Health Survey (ECRHS) framework, as dichotomous definitions could be less appropriate in the study of chronic diseases. The aims of this study were to assess the value of this asthma score in comparison with other definitions of asthma in another population setting, using as criteria bronchial hyperresponsiveness (BHR) to methacholine and diagnosed asthma, and the association of these definitions to known risk factors of asthma. METHODS: We used the ECRHS questionnaire on 2063 Brazilians, aged 23-25 years, and measured their BHR. We assessed the positive and negative likelihood ratios (PLR and NLR) of the asthma score (0-8), a three question score (ECRHS definition) and single asthma symptoms in relation to BHR and diagnosed asthma. RESULTS: The PLR were relatively low for all asthma definitions with odd ratios varying from 1.47 for asthma score to 5.50 for wheeze and waking with breathlessness without a cold. The NLR were near 1. The PLR were lower for assessments using the score than for dichotomous assessments or the ECRHS definition. The PLR increased with asthma scores, but the prevalence with higher scores was too low for useful analysis. The asthma score was slightly better for identifying associations from a set of known risk factors than the other two approaches. CONCLUSION: Our study provided little support for a greater validity of this asthma score over other asthma definitions, and only marginal advantage for identifying risk factors. PMID- 17845584 TI - Air pollution and seasonal asthma during the pollen season. A cohort study in Puertollano and Ciudad Real (Spain). AB - BACKGROUND: Many studies have demonstrated a positive association between air pollutants and emergency visits for asthma. However, few studies have included pollen when analysing this relationship in mild-moderate asthmatic patients. OBJECTIVE: To determine the importance of the pollutants such as ozone (O(3)), particles (PM(10)), nitrogen dioxide (NO(2)) and sulphur dioxide (SO(2)) in the clinical course of mild-moderate pollen-allergic asthmatic patients from two Spanish towns in La Mancha: Puertollano (high pollution levels) and Ciudad Real (low pollution levels). METHODS: We used a Poisson regression model to study a cohort of 137 patients from Puertollano and Ciudad Real during two pollen seasons (2000-2001) and analysed the relationship between air pollutant and pollen levels and daily symptoms, the medication used and peak-flow measurements. RESULTS: The number of asthma symptoms and the mean values of the PM(10), SO(2) and NO(2) levels were higher in Puertollano than in Ciudad Real. In Puertollano, the risk of asthma increased by 6% with a 3-day lag for PM(10), by 8% with a 3-day lag for O(3), by 4% with a 1-day lag for SO(2) and by 15% with a 3-day lag for O(3) when its values exceeded the health threshold (P < 0.05). CONCLUSIONS: The air pollution levels in Puertollano were associated with an increased risk of asthma symptoms in pollen-allergic asthmatic patients com pared with a similar group from Ciudad Real. PMID- 17845585 TI - Lifelong farm exposure may strongly reduce the risk of asthma in adults. AB - BACKGROUND: Farm exposures may protect against childhood asthma, hay fever and eczema. Whether farm exposures also confer protection in adult farmers remains unclear. Moreover, little is known about the role of timing of exposure. We assessed the effects of current and childhood farm exposures on asthma, hay fever and eczema in farmers and a rural nonfarming control population. METHODS: We conducted a cross-sectional questionnaire survey in 2509 farming families (response rate 78%) and 1001 nonfarming families (response rate 67%), which included 4288 farmers and 1328 nonfarmers. RESULTS: Farmers were less likely to have asthma symptoms, hay fever and eczema; no significant differences were observed among dairy, sheep and beef, and horticulture farmers. A combination of current and childhood exposure was more strongly associated with shortness of breath (OR 0.50, CL 0.39-0.66), wheeze (OR 0.60, CL 0.49-0.73), asthma medication (OR 0.48, CL 0.37-0.63); and asthma ever (OR 0.56, CL 0.46-0.68) than current exposure alone (OR 0.63, CL 0.47-0.84; OR 0.80, CL 0.65-0.99; OR 0.68, CL 0.51 0.9; OR 0.69, CL 0.56-0.85 respectively) or childhood exposure alone (OR 0.97, CL0.65-1.44; OR 1.01, CL 0.75-1.34; OR 0.78, CL 0.51-1.19; OR 0.87, CL 0.63-1.19 respectively). Moreover, the combined number of years of farm exposure in childhood and adulthood showed a dose-dependent inverse association with symptom prevalence. CONCLUSIONS: Although both current and childhood farm exposures may play a role in the observed low prevalence of asthma symptoms in adult farmers, continued long-term exposure may be required to maintain optimal protection. PMID- 17845586 TI - Predictive value of allergy and pulmonary function tests for the diagnosis of asthma in elite athletes. AB - BACKGROUND: Asthma is frequently found in athletes, often associated with rhinitis and allergy. AIM: To study the predictive value of allergy and pulmonary function tests for the diagnosis of asthma in athletes. SUBJECTS AND METHODS: Ninety-eight national preOlympic athletes underwent an accurate medical examination including a validated questionnaire for asthma and rhinitis, spirometric recordings and skin prick testing with a panel of the most frequent inhalant allergens. Bronchodilator and/or exercise challenge were also performed in asthmatic subjects. RESULTS: Clinical asthma was present in 20.4% of athletes, rhinitis in 35.3% (in 21.4% of cases alone and in 13.9% associated with asthma). Positive prick tests were recorded in 44.4% of athletes (in 60.5% of asthmatics, in 95.2% of rhinitics and in 21.0% of nonasthmatic - nonrhinitic subjects). Mean spirometric values and distribution of abnormal values were not different among asthmatics, rhinitics and nonasthmatics - nonrhinitic patients. Skin-tests positivity was not related to the abnormal spirometric data found in individual cases. Provocation tests with bronchodilators or exercise did not appear sensitive enough to diagnose mild forms of asthma in subjects with normal basal spirometric values. CONCLUSIONS: Allergy testing and spirometry should be performed routinely in athletes because of the high prevalence of allergy, rhinitis and asthma in this population. However, the predictive value of these tests and of the bronchial provocation tests performed in this study seems too low to document mild or subclinical asthma in athletes. PMID- 17845587 TI - Reliability of a new hand-held device for the measurement of exhaled nitric oxide. AB - BACKGROUND: Given the importance of airway inflammation in asthma, there has been an effort to incorporate inflammatory markers into its management. Measurement of fractional exhaled nitric oxide (FeNO) is a noninvasive marker of airway inflammation; however, the use of the available FeNO analyzer is limited by several factors including its cost and lack of transportability. The aim of this study was to compare the performance of a new hand-held FeNO measuring device (NIOX MINO) to the current clinical standard - the chemiluminescence FeNO analyzer (NIOX). METHODS: Subjects 6 years and older presenting to an allergy and asthma clinic underwent FeNO evaluation by NIOX and each of three NIOX MINOs. The mean of two acceptable measurements from the NIOX and the first approved measurement from each NIOX MINO were used for analysis. RESULTS: One hundred ten patients aged 6-86 years completed the study. Intrasubject FeNO levels obtained by each of the three NIOX MINOs revealed no significant difference between the measurements (P = 0.59). There was a very strong correlation between FeNO measurements by NIOX and by NIOX MINO (r = 0.98, P < 0.0001). The mean intrasubject FeNO difference between NIOX and NIOX MINO was -0.5 p.p.b. which was not statistically significantly different from zero (P = 0.21). CONCLUSIONS: Fractional exhaled nitric oxide measurements by the NIOX MINO showed a strong correlation and a high degree of agreement with the current standard stationary device. The NIOX MINO may be reliably used in clinical practice. PMID- 17845588 TI - CD-sens and clinical changes during withdrawal of Xolair after 6 years of treatment. AB - BACKGROUND: Many clinical trials with omalizumab, Xolair, have been reported but the treatment period has always been short, i.e. <12 months. After withdrawal, the clinical symptoms tend to return. A group of patients who stopped treatment after approx. 6 years allowed studies of the long-term effects of Xolair. METHODS: The patient's cat or mite allergen sensitivity was quantitated as basophil allergen threshold sensitivity, CD-sens, and immunoglobulin E (IgE) and IgE- and IgG4-antibodies were determined before start and during treatment withdrawal. Asthma severity was evaluated from forced expiratory volume (FEV), peak expiratory flow (PEF) and a questionnaire. RESULTS: At 6-14 months without Xolair 13 of the 18 cat and mite allergic asthmatics had either improved or remained the same as on treatment. Most of the patients were in a stable clinical condition reporting high quality of life, no increased nightly asthma attacks, no emergency visits as well as little or no increase in medication. The CD-sens to cat showed a peak 4 months after withdrawal but then decreased to levels below those of untreated patients with allergic asthma and at 12 months six of 14 had nonreactive basophils. Cat IgG4 antibody levels were higher than in cat allergics in general. CONCLUSION: Most of the patients 12-14 months had, after closing of 6 year Xolair treatment, a surprisingly mild asthma. Interestingly, and probably contributing to the clinical results, a downregulation of basophil, and presumably also mast cell, reactivity, was seen. PMID- 17845589 TI - Beclomethasone/formoterol vs fluticasone/salmeterol inhaled combination in moderate to severe asthma. AB - BACKGROUND: Recommended treatment for moderate to severe asthma is the combination of an inhaled corticosteroid and a long-acting beta(2)-agonist. The present study was designed to compare a new fixed combination of extrafine beclomethasone and formoterol, with the fixed combination fluticasone and salmeterol. METHODS: This was a phase III, multinational, multicentre, double blind, randomized, two-arm parallel groups, controlled study. After a 2-week run in period, 228 patients with moderate to severe asthma were randomized to a 12 week treatment with either beclomethasone 100 microg plus formoterol 6 microg or fluticasone 125 microg plus salmeterol 25 microg, both delivered two inhalations b.i.d. via a pressurized metered dose inhaler. RESULTS: The analysis of noninferiority on the primary outcome, morning peak expiratory flow in the last 2 weeks of treatment, showed no difference between groups (difference -3.32 l/min; 95% CI -17.92 to 11.28). A significant improvement from baseline in lung function, symptom score and rescue medication use was observed in both groups at all time points. Beclomethasone plus formoterol combination showed a significantly faster onset of bronchodilation when compared with fluticasone plus salmeterol with the difference maintained for up to 1 h postdosing. No differences were observed between treatments in the rate of asthma exacerbations, frequency of adverse events and overnight urinary cortisol/creatinine ratio. CONCLUSIONS: The new combination of extrafine beclomethasone plus formoterol is not inferior to the marketed combination of fluticasone and salmeterol in terms of efficacy and tolerability, with the advantage of a faster onset of bronchodilation. ( ClinicalTrials.gov number, NCT00394368). PMID- 17845590 TI - Cost-effectiveness of budesonide/formoterol for maintenance and reliever asthma therapy. AB - BACKGROUND: Budesonide/formoterol (Symbicort) Maintenance and Reliever Therapy (SMART) is an effective asthma-management approach that treats symptoms with rapid increases in budesonide/formoterol. The cost-effectiveness of SMART vs higher fixed-dose budesonide/formoterol or salmeterol/fluticasone is unknown. METHODS: This 6-month, double-blind study randomized patients with asthma uncontrolled by inhaled corticosteroids alone (n = 3335; age > or =12 years) to budesonide/formoterol 160/4.5 microg b.i.d. plus additional doses as needed (SMART), budesonide/formoterol 320/9 microg b.i.d. plus as-needed terbutaline, or salmeterol/fluticasone 50/250 microg b.i.d. plus as-needed terbutaline. Economic analysis, assuming health care and societal perspectives, applied 2004 UK and Australian unit costs to pooled resource-use data. The effectiveness variable was the rate of severe exacerbations/patient/6 months. RESULTS: Patients treated using the SMART approach experienced fewer severe exacerbations than fixed-dose budesonide/formoterol and salmeterol/fluticasone patients (0.12 vs 0.16 and 0.19 events/patient/6 months, respectively; P < or = 0.0048). Budesonide/formoterol (Symbicort) Maintenance and Reliever Therapy provided similar improvements in other markers of asthma control at a lower overall daily inhaled corticosteroid dose compared with fixed-dose treatment. Study drug costs accounted for a majority of both direct costs (DC; 78-87%) and total costs (TC; 50-63%) for all treatments, and were significantly lower in the SMART group compared with the fixed-dose groups (P < or = 0.0014). Direct and TC per patient/6 months were lower for SMART vs salmeterol/fluticasone (DC:-AUS$154, P < 0.0001; TC:-AUS$163, P = 0.0036;-87 pound sterling, P = 0.0026) and vs budesonide/formoterol using UK costs (DC:-73 pounds sterling, P < 0.0001; TC:- 91 pounds sterling, P = 0.0014). Costs tended to be lower for SMART vs budesonide/formoterol using Australian costs (DC:-AUS$35, P = 0.16; TC:-AUS$70, P = 0.20). Results were stable under sensitivity testing. Indirect resource use and cost were not significantly different between groups. CONCLUSION: Compared with higher fixed-dose budesonide/formoterol and salmeterol/fluticasone, SMART reduces the incidence of severe exacerbations at a lower or similar overall cost and can be considered a cost-effective treatment regimen. PMID- 17845591 TI - Association between obesity and asthma in a twin cohort. AB - BACKGROUND: Obesity is linked to asthma in a yet poorly understood manner. We examined the relationship between obesity and asthma in a population-based sample of twins. METHODS: From the cohorts born between 1953 and 1982, who were enrolled in The Danish Twin Registry, a total of 29 183 twin individuals participated in a nationwide questionnaire study, where data on height, weight and asthma were collected. Latent factor models of genetic and environmental effects were fitted using maximum likelihood methods. RESULTS: The age-adjusted risk of asthma was increased both in obese females, OR = 1.96 (1.45-2.64), P < or = 0.001 and in obese males, OR = 1.59 (1.08-2.33), P = 0.02. According to best-fitting models, the heritability for obesity was 81% in males and 92% in females, whereas the heritability for asthma was 78% and 68% in males and females respectively. The age-adjusted genetic liabilities to obesity and asthma were significantly correlated only in females, r = 0.28 (0.16-0.38). CONCLUSIONS: Obese subjects have an increased risk for asthma, which in females seems partly because of common genes. PMID- 17845592 TI - The link between the epidemics of obesity and allergic diseases: does obesity induce decreased immune tolerance? AB - There is increasing epidemiological evidence that obesity increases the risk of asthma, atopic, and autoimmune diseases. We hypothesize that the increase in these diseases is caused, at least in part, by decreased immunological tolerance as a consequence of immunological changes induced by adipokines (e.g. leptin and adiponectin) and cytokines [e.g. interleukin 6 (IL6) and tumor necrosis factor alpha (TNFalpha)] secreted by white adipose tissue. The increasing body weight increases the levels of circulating IL6, leptin, and TNFalpha. IL6 and leptin down-regulate the activity of regulatory T-lymphocytes (Tregs). Additionally, adiponectin, which decreases with increasing obesity, down-regulates the secretion of IL10 from macrophages and adipocytes. These changes in IL6, leptin, and IL10 decrease the regulatory effect of Tregs resulting in decreased immunological tolerance to antigens. In pregnant women, these obesity-induced immunological changes might be transmitted to the fetus by epigenetic inheritance thereby increasing the risk of atopic disease. We propose that obesity results in immunological changes resulting in decreased immunological tolerance to antigens and skewing of the immune system towards a Th2 cytokine profile increasing the risk of allergy and other immune-mediated diseases. Furthermore, this hypothesis offers a unifying explanation for the observation that older siblings appear to confer protection against atopic diseases, preeclampsia, and certain autoimmune diseases. More studies are definitely needed to explore further the immunological effects of obesity and its possible effects on allergic disease. PMID- 17845593 TI - When mild asthma requires extracorporeal membrane oxygenation in a young child. PMID- 17845594 TI - Allergy to Muscari comosum bulb. PMID- 17845595 TI - Autoimmune urticaria at 3 years of age diagnosed by puncture skin test using autologous serum. PMID- 17845596 TI - Salbutamol, terbutaline and pirbuterol allergy in an asthmatic patient. PMID- 17845597 TI - Anaphylaxis caused by allergen sublingual immunotherapy? PMID- 17845598 TI - Oestrus expression and ovarian function in repeat breeder cows, monitored by ultrasonography and progesterone assay. AB - Ovarian ultrasonography and plasma progesterone levels were monitored in 37 lactating Holstein cows with a history of repeat breeding; the data obtained were analysed in conjunction with clinical and behavioural signs, to identify the aetiology of the syndrome. Differences were detected between RBCs displaying apparently normal cycles and others with irregular cycles. There were also differences in heat expression; a large number of repeat breeder cows (RBCs, 50%) displayed delayed or silent oestrus. Ovarian disorders were common in RBCs, and included ovarian cysts, mistimed AI, subluteal progesterone levels, luteal dysfunction or ovulation defects. Both ultrasonography and plasma progesterone assays are useful tools for ascertaining the aetiology of the repeat breeder syndrome. PMID- 17845599 TI - Size distribution of dispersed luteal cells during oestrous cycle in Angora goats. AB - The present study examines the size distribution of the goat steroidogenic luteal cells throughout the oestrous cycle. Corpora lutea (CL) were collected after laparatomy on days 5, 10 and 16 of the oestrous cycle. Luteal cells were isolated from CL by collagenase digestion. Steriodogenic luteal cells were identified by staining of the cells for 3beta-hydroxysteroid dehydrogenase activity, a marker for steroidogenic cells. Luteal cells having steroidogenic capacity covered a wide spectrum of sizes, ranging from 5 to 37.5 microm in diameter. There was a significant increase in mean cell diameters (p < 0.01) as CL aged. The mean cell diameter on day 5 was 11.55 +/- 0.12 microm, which was significantly increased and reached up to 19.18 +/- 0.24 mum by day 16 of the oestrous cycle. The ratio of large to small luteal cells was 0.06:1.0 on day 5 of the oestrous cycle. This ratio increased to 0.78:1.0 by day 16 of the oestrous cycle. Luteal cell size on days 5, 10 and 16 of the oestrous cycle reached its maximum at 7.5, 10 and 35 microm in diameter, respectively. Development of CL is associated with an increase in luteal cell size in goats. It is likely that small luteal cells could develop into large luteal cells as CL becomes older during oestrous cycle in goats. PMID- 17845600 TI - Effects of body condition and protein supplementation on LH secretion and luteal function in sheep. AB - In ruminants, nutrition is one of the exogenous inputs affecting reproductive function at different levels of the hypothalamic-hypophyseal-gonadal axis. However, the exact mechanisms or even the identification of the signalling metabolic compounds by which nutrition affects reproductive function still need further clarification. The role of static body condition (BC) and its interaction with a short-term protein supplementation (PL), on secretion of metabolic hormones [growth hormone (GH), insulin and insulin-like growth factor-1 (IGF-1)], as well as on secretion of LH and progesterone (P4) was evaluated in sheep. Twenty-four Rambouillet ewes divided into two groups, with lower (LBC) and higher body condition (HBC), were randomly assigned within BC to one of two PL levels: low (LPL, 24% of crude protein; 14 g/animal/day), and high (HPL, 44% of crude protein; 30 g/animal/day). The secretion of GH, insulin, IGF-1 and LH was evaluated on day 10 of the oestrous cycle; appearance and timing of oestrous behaviour were previously detected using rams. Progesterone secretion was evaluated on day 13 of the same cycle. No differences were found (p > 0.05) between PL groups on serum GH concentrations during the sampling period (overall mean of 4.0 +/- 0.3 ng/ml), but a trend for lower values in HBC sheep was found (3.6 +/- 0.4 vs 4.4 +/- 0.4 ng/ml, p = 0.06). A BC effect was observed (p < 0.05) on serum IGF-1 level, with higher values in HBC sheep (p < 0.05). Neither BC nor PL affected (p > 0.05) secretion of LH and the number of corpora lutea, nor serum P4 and insulin concentrations. Results indicate a predominance of the static component of nutrition on sheep metabolic hormone responses, GH and IGF-1, with no effect of short-term PL on secretion of pituitary and ovarian hormones as well as luteal number and activity. PMID- 17845601 TI - Evaluation of the Karras spermdensimeter in relation to the Neubauer counting chamber for sperm concentration measurement in boar semen. AB - The correct measurement of spermatic concentration in boar semen is one of the basic tasks routinely performed at the Swine Artificial Insemination Center (CIAS). This article explains two experiments whose objectives were: Experiment 1: This trial had two objectives: (1) to evaluate the precision of the spermdensimeter (SPM) with relation to the Neubauer count chamber (CN) which is considered the standard technique in the field and (2) to correct the scale on the SPM table. Experiment 2: This trial also had two objectives: (1) to evaluate the time and repetitions required in the SPM and (2) to compare the SPM adjusted table produced in Expt 1 with the SPM standard table. The methods in Expt 1 were used to measure total spermatic concentration in 141 boar ejaculates. The average spermatic concentrations (10(6) spermatozoids/ml) and average dose number were 229.1 and 22.6 for CN, and 283.6 and 28.0 for SPM. These results indicate that the SPM has a tendency to overestimate spermatic concentration with relation to the CN. The SPM produced a smaller coefficient of variation and needed lesser examination time than the CN (p < 0.05). The SPM adjusted table created in Expt 1 produced similar results as the SPM and CN standard tables (2.96 billion live spermatozoids/dose vs 2.36 billion live spermatozoids/dose). Incorporation and evaluation of supplemental data from other CIAS regarding the use of the SPM adjusted table in the field entitled 'Adjusted Table for Karras Spermdensimeter LPS-FMVZ-USP' would be valuable to prove its efficiency. PMID- 17845602 TI - Infertility in a dog due to proximal cytoplasmic droplets in the ejaculate: investigation of the significance for sperm functionality in vitro. AB - A 4-year-old Basque Shepherd male dog was presented for breeding soundness evaluation after the dog failed to impregnate the three bitches he had mated. Clinical examination showed no anomaly of the reproductive system. Semen evaluation showed normal sperm count (640 x 10(6)), 80% had progressively motile spermatozoa, and 96% had morphologically abnormal sperm of which 84% had proximal cytoplasmic droplet and 12% had proximal droplet plus other anomaly. A zona pellucida-binding assay, using canine oocytes derived from frozen-thawed ovaries, was performed in order to investigate the zona-binding ability of dog spermatozoa with proximal cytoplasmic droplets. For the zona pellucida-binding assay, ovaries were thawed and minced in phosphate-buffered saline + 0.4% bovine serum albumin, the oocytes recovered were divided into two groups of 35-40 oocytes to be, respectively, used with the infertile dog and with a control fertile dog. Spermatozoa were capacitated in Canine Capacitating Medium (CCM) at 38.5 degrees C and 5% CO(2) in air for 2 h before oocyte insemination. Groups of five to six oocytes placed in 45 microl droplets of CCM were incubated for 1 h. Afterwards, 5 microl of CCM containing 25,000 spermatozoa were added to each droplet and co incubated for 2 h before fixation and evaluation of the complexes. After oocyte insemination, sperm motility and viability were evaluated: the sample from the infertile dog had 85% sperm motility with fast and linear progressive movement, and sperm viability of 92%. The sample from the control dog showed 40% sperm motility with fast and highly curvilinear and erratic movement, high degree of sperm agglutination and sperm viability of 32%. For the infertile dog the mean number of bound spermatozoa/oocyte was 0.33 whereas for the control dog it was 1.80. It was concluded that dog sperm with proximal cytoplasmic droplets seem to lack normal capacitating ability in vitro, and consequently, they may have reduced capacity to bind to the zona pellucida of canine oocytes. PMID- 17845603 TI - Practical techniques for bovine sperm simultaneous fluorimetric assessment of plasma, acrosomal and mitochondrial membranes. AB - This experiment was performed to develop and validate practical techniques for simultaneous evaluation of the integrity of plasma and acrosomal membranes, as well as mitochondrial function in bovine spermatozoa using associations of fluorescent probes. Four protocols of fluorescent probes association were defined: protocol 1: propidium iodide (PI), fluorescein isothiocyanate-conjugated Pisum sativum agglutinin (FITC-PSA) and rhodamine 123; protocol 2: PI, FITC-PSA and MitoTracker Green FM (MITO); protocol 3: PI, Hoechst 33342 (H342), FITC-PSA and CMXRos; and protocol 4: PI, H342, FITC-PSA and JC-1. Three ejaculates from each of the four bulls (n = 12) were utilized, showing sperm motility >/=80% and abnormal morphology /=35 mm pre-ovulatory follicle, with uterine oedema and a relaxed cervix. Ten mares were assigned to the two groups for 32 cycles in Bus1 and 52 cycles in Control, two mares received only Bus1 for three cycles, and one mare was assigned to Control for three cycles. Mares treated with buserelin received 6 ml of SUPREFACT s.c. (1.05 mg/ml buserelin acetate), and no treatment was given in Control. The ovulation rate between 24 and 48 h was higher (p < 0.0001) in Bus1 (31/35) than in Control (15/55). In Experiment 2, the condition of inducing ovulation with 6 ml SUPREFACT s.c. (Bus2) or 1500 ui human chorionic gonadotropin were identical to the first study. Forty-nine mares of ages 2-21 years, were used for 120 cycles, 56 cycles were assigned to Bus2, and 64 cycles were induced with 1500 IU human chorionic gonadotropin i.v. No significant difference was found in the ovulation rate on day 2 (38/56, 50/64), or in the fertility rate (19/48, 26/57). No negative effect of the treatment was observed with repeated buserelin administration in either study during the breeding season. We can conclude that a single administration of buserelin induces ovulation in the mare, under suitable conditions for veterinary practitioners. PMID- 17845613 TI - Ca2+ cascade and meiotic resumption of the caprine primary oocyte. AB - In this study, we investigated the fluctuations of concentration of intracytoplasmic free Ca(2+) during in vitro maturation of caprine primary oocytes and its role in meiotic resumption. Oocytes that were extracted from caprine ovaries were cultured and allowed to mature in vitro to determine their developmental stages including germinal vesicle (GV), germinal vesicle breakdown (GVBD), metaphase of the first meiotic division (MI) and metaphase of the second meiotic division (MII). Intracytoplasmic free Ca(2+) turnovers of caprine oocytes at these different developmental stages were measured using the calcium fluorescent probe Fura-2/AM (C(44)H(47)N(3)O(24)) to investigate the dynamics of cytosolic free Ca(2+) during in vitro maturation of oocytes and the role of Ca(2+) in inducing the initiation of meiotic resumption of oocytes. Moreover, the oocytes were cultured in Ca(2+) culture medium and Ca(2+)-free culture medium to examine the effect of extracellular Ca(2+) on the oocyte maturation. The results indicated that Ca(2+) concentrations at GV, GVBD, MI and MII stages were 78.06, 147.41, 126.97 and 97.73 nmol/l, respectively, and that 86.30% of oocytes remained at the GV stage and no oocyte developed to MII in Ca(2+)-free culture medium, and 1.1% of oocytes stayed at the GV stage and 83.5% of oocytes developed to MII in Ca(2+) culture medium. These results suggest that the occurrence of GVBD and cell cycle progression to MI and MII stages are closely related to Ca(2+), and that extracellular Ca(2+) performs a specific function for the initiation of meiotic resumption in caprine oocytes. PMID- 17845615 TI - In vivo long-term effects of retinoic acid exposure in utero on induced hyperplastic epidermal foci in murine skin. AB - Adult Naval Medical Research Institute (NMRI) mice, after prenatal exposure to retinoic acid (RA), were treated with a standard two-stage skin carcinogenesis regime to characterize hyperplastic epidermal foci that precede the appearance of cutaneous papillomas, and to investigate the in vivo long-term action of RA on adult mouse skin treated with DMBA (7,12 dimethyl benz[a]anthracene) and TPA (12 O-tetradecanoylphorbol 13-acetate). The results demonstrate that RA administered to pregnant mice had a long-term inhibitory action on the cell differentiation and development of hyperplastic lesions occurring prior to cancer on the adult skin of their offspring as well as a stimulatory effect on cell proliferation of these hyperplastic lesions. PMID- 17845616 TI - Repeatability and reproducibility of numerical rating scales and visual analogue scales for canine pruritus severity scoring. AB - Although they are used frequently in veterinary dermatology, the reliability of canine pruritus severity scales has not been reported. The objective of this study was to evaluate the reliability of pruritus severity numerical rating scales (NRS) and pruritus severity visual analogue scales (VAS). Videos of 16 dogs were evaluated for pruritus severity by 24 observers utilizing three NRS and three VAS. Intraobserver repeatability and interobserver reproducibility were evaluated with Cohen's kappa and Kendall's rank correlation statistics, respectively. The repeatability of pruritus severity NRS was fair, with mean Cohen's weighted kappa (kappa(w)) values ranging from 0.49 to 0.60. The mean Kendall's rank correlation coefficient (t) for the three VAS ranged from 0.62 to 0.73. The reproducibility of mid-range pruritus severity ranks was poor with both scale types. Scales describing overall pruritus severity were found to be reliable most consistently. Neither NRS nor VAS displayed the degree of reliability desired in a health measurement scale. Interpretation of research results evaluating canine pruritus severity with NRS and VAS scales should account for suboptimal reliability. PMID- 17845617 TI - Development of an owner-assessed scale to measure the severity of pruritus in dogs. AB - Assessment of pruritus is critical in dermatological history taking, both for initial diagnosis and for monitoring treatment. Various methods of assessing pruritus in the dog have been described but none have been validated. In this study, four different pruritus scales were initially assessed: a 0-5 numerical scale; a scale containing six categories of pruritic behaviours; a scale with six basic descriptors of severity; and a visual analogue scale with severity descriptions at either end. One hundred and sixteen owners were asked to grade their dog's pruritus with each of the four scales given to them in a randomized order, and asked which they thought was easiest to use, which was most accurate in assessing their dog's pruritus level, and which two scales they would combine to make a superior scale. Pruritus scores from different scales were highly correlated with each other, but scores were significantly higher with the severity and numerical scales compared to the behaviour scale. Based on the clients' responses, a new scale was developed that combined features of the behaviour and severity-based scales with the visual analogue scale. When tested on 166 different owners, 98% thought it was easy to use and accurate in assessing their dog's pruritus level. In 44 dogs, independent scores obtained by two owners were highly correlated (R = 0.8; P < 0.0001), confirming the scale's repeatability. The new scale proved to be an easy and repeatable method for owners to determine the severity of pruritus in their dog. PMID- 17845618 TI - A case-control study of risk factors for canine atopic dermatitis among boxer, bullterrier and West Highland white terrier dogs in Sweden. AB - Environmental and dietary risk factors for the development of canine atopic dermatitis (CAD) in the high-risk breeds of boxer, bullterrier and West Highland white terrier were assessed in a case-control study. A logistic regression model was developed to evaluate their relative importance in 58 cases from 12 practices in Sweden and 61 unaffected controls, matched to cases by breed and year of birth. The final model included a random error term for 'examining veterinarian', as dogs from the same practice were not considered independent. No effect of gender, season of birth, environment, vaccination or de-worming practices on the odds of developing CAD was detected. The main finding was that feeding a diet including noncommercial products to the bitch during lactation had a protective effect on the development of CAD in her offspring; the odds of developing CAD were twice as high among offspring from bitches that were not exposed to home made/noncommercial diets [95% confidence interval (CI) of the odds ratio: 1.2 3.8]. The population attributable fraction for not feeding home-made diets to the lactating bitch was estimated as 0.4 (95% CI: 0.04-0.63). Randomized controlled clinical trials are needed to further support the finding of a potential protective role of diet in CAD development. PMID- 17845619 TI - Malassezia spp. overgrowth in allergic cats. AB - A series of 18 allergic cats with multifocal Malassezia spp. overgrowth is reported: atopic dermatitis was diagnosed in 16, an adverse food reaction in another and one was euthanized 2 months after diagnosis of Malassezia overgrowth. All the cats were otherwise healthy and those tested (16 out of 18) for feline leukaemia or feline immunodeficiency virus infections were all negative. At dermatological examination, multifocal alopecia, erythema, crusting and greasy adherent brownish scales were variably distributed on all cats. Cytological examination revealed Malassezia spp. overgrowth with/without bacterial infection in facial skin (n = 11), ventral neck (n = 6), abdomen (n = 6), ear canal (n = 4), chin (n = 2), ear pinnae (n = 2), interdigital (n = 1) and claw folds skin (n = 1). Moreover, in two cats Malassezia pachydermatis was isolated in fungal cultures from lesional skin. Azoles therapy alone was prescribed in seven, azoles and antibacterial therapy in eight and azoles with both antibacterial and anti inflammatory therapy in three of the cats. After 3-4 weeks of treatment, substantial reduction of pruritus and skin lesions was observed in all 11 cats treated with a combined therapy and in five of seven treated solely with azoles. Malassezia spp. overgrowth may represent a secondary cutaneous problem in allergic cats particularly in those presented for dermatological examination displaying greasy adherent brownish scales. The favourable response to treatment with antifungal treatments alone suggests that, as in dogs, Malassezia spp. may be partly responsible for both pruritus and cutaneous lesions in allergic cats. PMID- 17845620 TI - Use of lime sulphur and itraconazole to treat shelter cats naturally infected with Microsporum canis in an annex facility: an open field trial. AB - Dermatophytosis is the most common contagious and infectious skin disease of cats. It is of particular importance in animal shelters because it is a known zoonosis, highly contagious, and easily transmitted. In this open clinical trial, 58 cats with confirmed Microsporum canis dermatophytosis and 32 uninfected bonded pairs or littermates were treated with a combination of 21 days of oral itraconazole (10 mg kg(-1)) and twice weekly lime sulphur rinses until cured. Cats were not clipped in this treatment programme. Fungal cultures were obtained once weekly on all cats, and cats were considered cured when they had two consecutive negative weekly fungal cultures. Cats were held in the facility and received continued topical treatment until the fungal cultures were finalized. None of the cats developed oral ulcerations as a result of grooming the lime sulphur rinses. Oral ulcerations only developed in cats with clinical signs associated with upper respiratory disease. None of the uninfected cats living in contact with infected cats became culture positive or developed skin lesions. When data were examined retrospectively and the number of days to finalize the cultures was subtracted (21 days) from the total number of days the cats were housed in the annex, the mean number of days of treatment required for cure was 18.4 +/- 9.5 SEM (range 10-49 days). Cats with more severe infections required longer therapy. In this shelter, the combination of oral itraconazole and topical lime sulphur rinses for the treatment of dermatophytosis was effective and safe. PMID- 17845621 TI - Cutaneous reactive histiocytosis in dogs: a retrospective evaluation of 32 cases. AB - Thirty-two cases of canine cutaneous histiocytosis were retrospectively evaluated. Median age at onset was 4 years. Lesions included nodules and plaques affecting the head/face, trunk and limbs, and erythema, swelling and depigmentation of the nasal planum/nares. Systemic involvement was not ruled out in all cases. All dogs had complete resolution of dermatological lesions after initial treatment (median 45 days). Initial treatment included prednisone +/- antibiotics (12 of 32 dogs), prednisone and tetracycline/niacinamide (four of 32), prednisone and azathioprine (three of 32), tetracycline/niacinamide +/- vitamin E/essential fatty acids (six of 32), antibiotics +/- antihistamines (three of 32), cyclosporine and ketoconazole (one of 32), topical therapy (two of 32), and no treatment (one of 32). Seventeen dogs received maintenance therapy which consisted of tetracycline/niacinamide +/- vitamin E/essential fatty acids (12 of 17), cyclosporine/ketoconazole (two to three times a week) (two of 17), azathioprine daily (one of 17), prednisone/azathioprine (two times a week) (one of 17), and prednisone daily (one of 17). Median follow up was 25 months. Nine dogs had a recurrence of cutaneous histiocytosis (median days to recurrence 130 days), with seven of nine having more than one recurrence. At study completion, six dogs were deceased (no lesions at the time of death) and 26 of 32 were alive with no lesions. Ten of 26 dogs were on maintenance treatment (eight tetracycline/niacinamide, one azathioprine, one vitamin E). Previous dermatological disease and season had no detectable influence on recurrence. Recurrence was significantly more likely in dogs with nasal planum/nares lesions than dogs without these lesions. Tetracycline/niacinamide was an effective treatment option for dogs in this study population. PMID- 17845622 TI - Aetiology of canine otitis externa: a retrospective study of 100 cases. AB - The objective of this retrospective study was to investigate in 100 dogs with otitis externa (OE) the possible associations between signalment, history, clinical and laboratory findings and the various primary, secondary and perpetuating causative factors of ear canal inflammation. The age of the dogs ranged from 3 months to 14 years (median: 4.75 years) and they included 45 males and 55 females. Cocker spaniels, Jura des Alpes and Brittany spaniels were significantly overrepresented among dogs with OE when compared to the hospital canine population. In the majority of the cases, OE was chronic-recurrent (63%) or bilateral (93%). Allergic dermatitis (43/100 dogs), grass awns (12/100) and otoacariasis (7/100) were the most common primary causative factors; no primary factor could be incriminated in 32 cases and more than one was found in three dogs. Malassezia spp. (66/100 dogs), cocci (38/100) and rods (22/100) were the secondary causative factors, while ear canal stenosis (38/100) and tympanic membrane perforation-otitis media (25/100) were the most important perpetuating factors. Atopic dermatitis and adverse food reactions-associated OE was more common in females and dogs with a history of pruritic skin disease, while grass awn-induced OE occurred in cocker spaniels and acute cases. Tympanic membrane perforation was less frequent in atopic dermatitis and adverse food reactions associated OE, but more common when otoscopic and ear canal cytological examination revealed the presence of grass awns and rods, respectively. Finally, cocci overgrowth was positively associated with ear canal stenosis. PMID- 17845623 TI - Malassezia slooffiae-associated dermatitis in a goat. AB - An adult male Pygmy goat with a history of losing hair and declining body condition was euthanized, and a complete diagnostic work-up was performed. The animal showed diffuse alopecia on the dorsal and lateral sides of thorax and abdomen, proximal legs, neck and face. Histology revealed diffuse orthokeratotic hyperkeratosis, epidermal hyperplasia and perivascular dermatitis. Broad-based budding yeasts and hyphae were visible in the keratin layer. Malassezia slooffiae was identified in the skin by polymerase chain reaction amplification of part of the large subunit rRNA gene using broad-range fungal primers and DNA sequencing. This is the first report of M. slooffiae-associated dermatitis in goats. PMID- 17845624 TI - Pemphigus foliaceus-like drug reaction in a 3-month-old crossbreed dog treated for juvenile cellulitis. AB - Two weeks after administration of routine vaccinations, a 3-month-old, male crossbreed dog developed cutaneous lesions that were clinically and histopathologically consistent with a diagnosis of juvenile cellulitis. The patient was treated with systemic antibacterial, antibacterial ophthalmic ointment and nonsteroidal anti-inflammatory drugs. Within 1 week, new skin lesions that were clinically, histopathologically and immunohistochemically consistent with pemphigus foliaceus developed. The latter completely resolved following drug withdrawal, suggesting a pemphigus foliaceus-like drug reaction. However, the initial lesions persisted and required glucocorticoid therapy to effect resolution. To the authors' knowledge, this is the first reported case of a puppy developing juvenile cellulitis followed by a pemphigus foliaceus-like reaction shortly thereafter, in response to drug therapy. PMID- 17845625 TI - Multiple cutaneous ganglioneuromas in a dog. AB - A 3-year-old male Labrador retriever dog was presented with multifocal small cutaneous nodules, distributed mainly over the thoracic wall, the flank and the scrotum. The dog was otherwise in good health and had no significant past medical history. Radio- and sonographic examination revealed no evidence of internal tumours, including endocrine tumours. Histological examination of two excised samples revealed round, non-ulcerated nodules in the superficial corium, characterized by two different neoplastic cell components and mild inflammation. The first tumour cell population showed histomorphological characteristics of mature ganglion cells; the second featured small, spindle-shaped tumour cells with scant cytoplasm. Both neoplastic cell components expressed vimentin, neurofilament protein, pan-neuronal neurofilament, amyloid-precursor protein and chromogranin A. In addition, the spindle-shaped tumour cells were positive for 2', 3'-cyclicnucleotide 3'-phosphodiesterase. The findings had many histological and immunohistochemical features in common with primary cutaneous ganglioneuromas in humans, enabling the canine tumours to be also classified as multiple cutaneous ganglioneuromas. PMID- 17845626 TI - Skin fragility syndrome in a cat with feline infectious peritonitis and hepatic lipidosis. AB - A 6-year-old spayed female domestic shorthair cat with a 3-week history of inappetence, weight loss, and hiding was examined. A palpable abdominal fluid wave, dehydration, and a small tear on the left flank were noted during initial examination. When the cat was gently restrained for blood sampling, the skin on the dorsal neck tore, leaving a 15 cm x 7 cm flap of skin. Clinicopathological abnormalities included nonregenerative anaemia, hypoalbuminaemia, increased globulin concentration, and mildly elevated aspartate aminotransferase and alkaline phosphatase activities. Abdominal fluid was viscous and had a total protein of 5.3 g dL(-1) with 316 cells microL(-1), consistent with a modified transudate. Cytology of the abdominal fluid revealed 86% nondegenerate neutrophils, 13% macrophages, and 1% small lymphocytes. Histopathological evaluation and indirect immunohistochemistry confirmed a diagnosis of feline infectious peritonitis, hepatic lipidosis and feline skin fragility syndrome. Feline skin fragility syndrome has not previously been reported in association with feline infectious peritonitis (FIP). Its inclusion as a clinical sign associated with FIP may facilitate a diagnosis. PMID- 17845627 TI - Proliferative and necrotizing otitis externa in four cats. AB - Proliferative and necrotizing feline otitis externa is a rare disorder of unknown aetiology. This condition was diagnosed by skin biopsy in three adult domestic shorthair cats (3-5 years old) and one kitten (6 months old). The affected cats had large tan to dark brown-black coalescing plaques covering the concave surface of the pinnae and external ear canals. Friable material from the plaques and a thick exudate occluded the ear canals. The cats had a secondary bacterial and/or yeast otitis. Prior to the histopathological diagnosis, all cats received numerous otic preparations as well as oral antibiotics and corticosteroids without resolution. Histologically, all cases had strikingly similar changes; acanthosis with pronounced hair follicle outer root sheath hyperplasia and neutrophilic luminal folliculitis, follicular keratosis and individually necrotic keratinocytes in the outer root sheath of hair follicles. One case was documented via skin biopsy to have persisted for 4 years. The adult cats were treated with topical 0.1% tacrolimus and all showed marked improvement although one cat was lost to follow up. The lesions completely resolved with topical tacrolimus alone in one cat and topical tacrolimus in addition to oral prednisolone in another cat. PMID- 17845628 TI - Drug-associated canine pemphigus vulgaris? Who knows! PMID- 17845631 TI - The long-term survival of simultaneous pancreas and kidney transplant with basiliximab induction therapy. AB - Interleukin-2 receptor (IL2R) antibody has emerged as an attractive induction therapy for organ transplant. However, the long-term outcome of basiliximab induction in simultaneous pancreas and kidney (SPK) transplant remains speculative. We retrospectively analyzed the long-term survivals of 91 consecutive SPK recipients with basiliximab as induction, combination of steroid, tacrolimus (TAC) and mycophenolate acid (MFA)--either mycophenolate mofetil (MMF) or sodium mycophenolate (myfortic) as maintenance. At one, three, five, and seven yr, the actual patient survival rate were 91.2%, 90.3%, 88.1%, and 88.2%, respectively; kidney graft survivals were 90.1%, 84.7%, 78.6%, and 70.6%, respectively; and pancreas graft survivals were 86.8%, 80.6%, 71.4%, and 58.8% respectively. There was a low incidence of rejection and CMV infection. Basiliximab induction with TAC, MFA, and steroid maintenance therapy can provide excellent long-term outcome for SPK recipients. PMID- 17845632 TI - Symptom experience after lung transplantation: impact on quality of life and adherence. AB - BACKGROUND: Patients' perceptions of immunosuppression- related symptom experience may impact on quality of life (QoL) and medication adherence. METHODS: A total of 308 lung transplant recipients were screened for study inclusion. Two hundred eighty-seven patients (response rate 93%) completed a 91-item questionnaire consisting of subscales focusing on symptom experiences (frequency and distress), and adherence. QoL was assessed by a 40-item standardized instrument. Impact of symptom experiences on QoL and adherence were assessed. Potential determinants of immunosuppression induced symptom experiences were evaluated. RESULTS: The most frequent reported symptoms were tremor (70%) and hirsutism (68.1%), whereas Cushingoid appearance (38.6%) and muscle weakness (31.9%) appeared to be the most distressing symptoms. Women (p < 0.001) and younger patients (<40 yr; p < 0.0001) reported a significantly higher level of symptom experience compared with their counterparts respectively. Symptom experiences negatively influenced QoL in all dimensions (p < 0.006). Those who described experiencing adverse effects reported significantly more "drug holidays" (p < or = 0.004) compared with those reporting minor frequent adverse effects. Patients' self-reported strategies to reduce adverse effects were to postpone medication intake (30%), to drop doses (8%), or to reduce doses (9%). CONCLUSIONS: This study establishes a relationship between patients' perceptions of immunosuppression-related symptom experiences and the impact on QoL and adherence. Immunosuppression is accompanied by significant adverse effects in both symptom frequency and distress. Most frequently experienced symptoms do not necessarily have the greatest impact on perceived distress, and vice versa. High levels of adverse effects tend to negatively influence patients' QoL and adherence. Future research is required to understand the relationship of these complex variables. PMID- 17845633 TI - Transplant reno-vascular stenoses associated with early erythropoietin use. AB - BACKGROUND AND OBJECTIVES: This report describes an unusual presentation of severe hypertension (HTN) in a subset of pediatric kidney recipients treated with a steroid avoidance pediatric renal transplantation protocol. The HTN was secondary to atypical, reno-vascular abnormalities (RVA) of the transplanted vasculature, temporally associated with erythropoietin (EPO) use. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: To investigate the clinical significance underlying this event, a retrospective clinical study of 100 pediatric renal transplants was undertaken (50 steroid-free and 50 matched steroid-based controls), with peripheral blood transcriptional analysis of four RVA patients and controls. RESULTS: Regardless of a higher observed incidence of anemia (p < 0.001) and greater overall EPO usage in the first post-transplant year in steroid free patients, the incidence of new-onset HTN at one yr was significantly less in the steroid-free cohort (p = 0.03). Nevertheless, early EPO (first week post transplant) was significantly associated with the combinatory findings of new onset HTN (p = 0.03) and RVA (p = 0.007). Molecular mechanisms of RVA injury were investigated further by peripheral blood cDNA microarray gene expression profiling. A panel of 42 transcripts differentiated patients with RVA and HTN from three sets of matched controls, with and without HTN and EPO use, with 100% concordance (p < 0.001). The biological processes governed by these significant genes suggest a role for EPO regulation of growth factor receptor ubiquitination as a putative mechanism for renal vascular injury. CONCLUSION: This study cautions against the use early post-transplant use of EPO in immunosuppression regimens with steroid minimization/avoidance, which may have an increased incidence of post-transplant anemia. PMID- 17845634 TI - Renal transplant outcome in high-cardiovascular risk recipients. AB - BACKGROUND: Cardiovascular (CV) disease is the foremost cause of mortality and an important cause of morbidity in renal transplant recipients. The disease burden is likely to increase as older patients are accepted for transplantation. The outcome of these high-CV risk patients after renal transplantation, especially with known pre-transplant coronary artery disease (CAD), has not been studied. Hence, we looked at the CV outcome in patients with known pre-transplant CAD. METHODS: All renal transplants performed between 1998 and 2002 at our center, followed up to 2005, were divided into high- and low-risk groups, based on the presence of one or more of the following: pre-transplant angina, myocardial infarction, and positive coronary angiogram. The two groups were compared for post-transplant cardiac events and patient and graft survival. The factors predictive of post-transplant cardiac events were also determined by Cox regression multivariate analysis. RESULTS: Forty-five patients (10.5%), out of 429, had post-transplant cardiac events; 31.3% in the high risk, and 6.5% in the low-risk group (p = 0.001). Five-yr patient survival was lower in the high-risk group (82.8% vs. 93.1%, p = 0.004), while five-yr overall graft survival and death censored graft survival were statistically not different (74.8% vs. 84.1%, p = 0.08 and 87.3% vs. 90%, p = 0.25). Forty-one percent of patients who were treated with angioplasty plus stenting or bypass graft prior to transplantation had post-transplant cardiac events, as compared with 28% of those without intervention in the high-risk group and 6.5% of patients in the low-risk group (p = 0.001). Age, pre-transplant cardiac disease, arrhythmias, and low-ejection fraction (< or = 40%) were significant independent predictors of post-transplant cardiac events. CONCLUSION: Post-transplant survival of high-CV risk patients (with known CAD) is lower than that of low-risk recipients but remains acceptable. Cardiac interventions may reduce perioperative risk but do not reduce the probability of post-transplant cardiac events to that of low-risk group. PMID- 17845635 TI - Influence of cytokine genes polymorphisms on long-term outcome in renal transplantation. AB - BACKGROUND: Recently, polymorphisms of cytokine genes have been associated with modified gene expression and increased cytokine production. We evaluated the influence of interleukin-10 (IL-10) gene G-1082A, tumour necrosis factor alpha (TNFalpha) gene G-308A and IL-6 gene G-174C polymorphisms on the rejection rate, renal function and long-term outcome in renal transplantation. PATIENTS AND METHODS: We studied n = 224 consecutive patients, who underwent renal transplantation at our centre from 1998 to 2001 (cadaveric: n = 175, living related: n = 49) followed up for 4.9 +/- 2.0 yr and n = 100 healthy volunteers. IL-10 gene G-1082A, TNFalpha gene G-308A and IL-6 gene G-174C polymorphisms were determined by polymerase chain reaction (PCR) amplification. RESULTS: The genotype distribution of the investigated polymorphisms was similar in patients and controls (ns). The age of donor and the recipient, the number of HLA mismatches and cold and warm ischemic time did not differ among patients with different genotypes (ns). No association between cytokine polymorphisms and the incidence of acute rejection episodes was detected (ns). The cytokine genotypes did not correlate with serum creatinine or creatinine clearance at any time during follow up (ns). Furthermore, there was no significant difference in the genotype frequencies among patients experiencing graft failure (ns). Patients with different cytokine gene polymorphisms showed similar outcomes in the Kaplan Meier analysis of graft survival (ns). Finally, cytokine polymorphisms had no influence on the acute rejection rate or graft outcome also in the subgroup of HLA-DR mismatched grafts (ns). CONCLUSION: Our results suggest that IL-10 gene G 1082A, TNFalpha gene G-308A and IL-6 gene G-174C polymorphisms are no major risk factors in renal transplantation. PMID- 17845636 TI - Quality of life and psychological well-being during and after left ventricular assist device support. AB - BACKGROUND: Left ventricular assist devices (LVAD) are increasingly being used to treat patients in end-stage heart failure to facilitate survival to cardiac transplant or as a bridge to myocardial recovery. The technical innovation of the LVAD has a significant benefit on the patients' physical functioning. However, within the United Kingdom, there has been no systematic evaluation of the psychological adjustment and quality of life (QoL) of patients currently living with an LVAD, or of the differences in QoL for patients who are either explanted or transplanted. AIM: To assess the differences in QoL and psychological adjustment for current LVAD patients, patients who have been transplanted from an LVAD and patients in whom the device has been explanted. METHODS: Twenty-two patients involved in an LVAD programme were recruited (18 men and four women; age range 18-60). Eight patients had an LVAD in situ, six patients had the LVAD explanted and eight had undergone transplantation. QoL and psychological functioning were assessed using previously validated measures. RESULTS: Although there were no significant differences between the three groups, there was a trend for the LVAD patients to have higher levels of anxiety and depression and a lower QoL compared with transplanted or explanted patients. CONCLUSIONS: For patients with an LVAD in situ, there was a trend for QoL and psychological functioning to be poorer than for transplanted and explanted patients. Larger studies will be needed to confirm these findings, but psychological assessment and interventions to reduce psychological morbidity and improve QoL will be important in these patients, particularly in view of the increasing numbers of LVADs being implanted and the possibility of their use for long-term "destination" therapy. PMID- 17845637 TI - Infectious complications associated with the use of rituximab for ABO incompatible and positive cross-match renal transplant recipients. AB - Immunosuppressive protocols for ABO-incompatible (ABOI) and positive cross-match (PCM) solid organ transplant (SOT) recipients have included the use of rituximab (RTX). Infectious complications (IC) have been reported after the use of RTX for other indications, but have not been well studied in the SOT population. We performed a retrospective review of IC occurring within six months of ABOI and PCM renal transplantation (RT) in recipients receiving RTX. Medical records were reviewed for bloodstream, lung, gastrointestinal tract, allograft, or soft tissue infection. Between July 2001 and December 2004, 34 ABOI or PCM RT were performed at University of Illinois at Chicago, 25 of which received RTX with plasmapheresis and antithymocyte globulin (ATG) (eight ABOI and 17 PCM). Among the RTX recipients, the rate of IC was 48% compared with 11% among historical controls who did not receive RTX (p = 0.107). There were 21 episodes of IC in 13 patients including skin and soft tissue infection (8), bloodstream infection (5), esophagitis (3), peritonitis (3), pneumonia (1), and colitis (1). There was no difference in the rate of rejection, graft survival or patient survival between the two groups. These data suggest that there is a trend toward an increased rate of IC with RTX therapy in ABOI and PCM RT recipients. PMID- 17845638 TI - Immunoassay determination of rapamycin: reliability of the method with respect to liquid chromatography mass spectrometric quantification. AB - Immunochemical assays represent a promising tool for quantification of immunosuppressants in organ transplanted patients, because they require small sample volumes and minimum sample pre-treatment; nevertheless considerations about method specificity, sensitivity and reproducibility cannot be overlooked. The present paper investigates the reliability of using the immunoparticle enzyme immunoassay (MEIA) for the quantification of blood rapamycin (RAPA) levels in therapeutic drug monitoring of renal transplanted patients with respect to a validated liquid chromatography tandem mass spectrometric (LC/ESI-MSMS) method, used as reference. Linearity of MEIA was tested over the range 0.0-30.0 ng/mL, with accuracy and precision within acceptable limits. Fifty-two blood samples were collected from 42 renal transplanted patients and analyzed simultaneously by both methods. The Pearson's regression analysis gave the following parameters: correlation equation [RAPA](MEIA) = 1.330 + 0.776 [RAPA](LC/ESI-MSMS), r = 0.8526, SD = 1.778, p < 0.0001. The obtained average rapamycin concentration was 8.8 +/- 3.4 ng/mL using MEIA and 9.6 +/- 3.7 ng/mL for LC/ESI-MSMS, with an overall underestimation of about 6% of the immunoenzymatic test. Accuracy of MEIA ranged from -33% to 36% with respect to the reference mass spectrometric method. Although immunoenzymatic test represents a fast and sufficiently accurate method for its use in clinical practice, specificity of the assay is still not sufficiently investigated and reference methods and/or Proficiency Testing Scheme should be used as external control. PMID- 17845639 TI - Long-term follow-up ABO-incompatible adult living donor liver transplantation in cirrhotic patients. AB - ABO-incompatible liver transplantation is usually contraindicated. The presence in the recipient of preformed anti-A/B antibodies located on endothelial cells raises the risk of antibody-mediated humoral rejection of the graft. We describe four successful cases of steroid withdrawal in adult patients who had living donor liver transplantation from ABO-incompatible donors. Antirejection therapy included multiple perioperative plasmapheresis, splenectomy, and a triple immunosuppressive regimen with tacrolimus, methylprednisolone (MPSL), and cyclophosphamide or mycophenolate mofetil (MMF). The maintenance dose of immunosuppression did not differ from that of ABO-identical cases. After transplantation, intrahepatic arterial infusion therapy with prostaglandin E1 (PG E1) was used. As a result, all four patients were able to achieve long-term graft survival without steroid use. They all have good liver function and are leading normal lifestyles. Our experience with these four patients suggests the feasibility of controlling humoral rejection and other complications in adult ABO incompatible living donor liver transplantations with intrahepatic arterial infusion of PGE1, splenectomy, and plasmapheresis with a regular base of immunosuppression protocol to prevent antibody-mediated humoral rejection. PMID- 17845640 TI - Methamphetamine use in deceased kidney donors impairs one-yr graft function. AB - BACKGROUND: Methamphetamine (MA) has cumulative deleterious effects on multiple organ systems. A history of MA exposure in kidney donors may affect adversely graft function in recipients. METHODS: Between September 2000 and March 2004, all deceased kidney donors were identified from the local registry (97 donors). Twenty donors (21%) with any MA exposure through history or toxicology were selected. Donors that did not fulfill UNOS standard criteria were excluded. Donor characteristics and subsequent recipient characteristics were retrospectively compared with a control group without MA exposure histories. The main outcome measure was mean serum creatinine at one-yr post-transplant (Cr365). Secondary outcome measures of delayed graft function and rejection episodes were reviewed. RESULTS: Baseline serum creatinine at seven d post-transplant were equivalent between groups (Cr7 = 2.5 +/- 2.0 vs. 2.8 +/- 3.4, p = 0.75). At one yr, Cr365 was significantly elevated in recipients of MA exposed kidneys compared with controls (1.9 +/- 1.0 vs. 1.4 +/- 0.4, p = 0.028). When adjusted for confounding variables, MA exposure lost its statistical significance (p = 0.07-0.09) as an independent predictor of increased Cr365. CONCLUSION: Donor MA exposure may be associated with increased Cr365 in recipients. Transplant centers can expect to encounter donors with MA use histories at rates higher that regional use rates. Larger studies may demonstrate MA exposure as an independent predictor of impaired graft function. PMID- 17845641 TI - Gallstone formation after pancreas and/or kidney transplantation: an analysis of risk factors. AB - Pancreas and kidney transplantation (SPK) is the treatment of choice for patients with type 1 diabetes mellitus and end-stage renal failure. Gallstones are common after SPK transplantation but little is known about the true incidence and etiology of gallstones in this group. We therefore evaluated the incidence of gallstones and the presence of transplant-related risk factors in patients after SPK and kidney transplantation alone (KTA). Data were evaluated of 56 consecutive patients who underwent SPK transplantation and compared the results with those of 91 consecutive nondiabetic patients who underwent KTA transplantation at the Leiden University Medical Center between 1987 and 1994. Of the 58 evaluable KTA patients, 20.7% developed gallstones during 7.7 yr of follow-up and in the SPK group 43.9% of the 41 evaluable patients developed gallstones during 7.1 yr of follow-up. Postoperative weight loss and cyclosporin A-related hepatotoxicity correlated with gallstone formation both in SPK and KTA patients. In addition, the duration of postoperative fasting and autonomic neuropathy correlated with gallstones in SPK patients. It is concluded that both in patients after SPK transplantation and in patients after KTA transplantation, the risk to develop gallstones is significantly increased. Physicians should be aware of the high incidence of gallstones in SPK recipients. PMID- 17845642 TI - Hemorrhagic cystitis: a retrospective single-center survey. AB - Severe hemorrhagic cystitis (HC) may be a life-threatening complication in allogeneic stem cell transplantation (SCT). In order to improve the strategies for prophylaxis and treatment, we retrospectively analyzed data on patients who underwent SCT at our center from 1990 through 2005. Patients with HC were identified through our database and their medical charts were reviewed. Grades 2 5 and 3-5 HC developed in 109/834 patients (13.1%) and 27/834 patients (3.2%), respectively. The frequency of HC decreased over the time from 18.0% in 1990-1992 to 9.5% in 2002-2005 (p = 0.005). HC started on a median of 35 (0-166) days post transplant and persisted for a median of 23 (2-270) days. Transplant-related mortality was 21% in patients without HC, 15% in those with HC of grade 2, 55% in those with grade 3, and 71% in patients with HC of grades 4-5 (p < 0.001). In multivariate analysis, the risk factors for HC were myeloablative conditioning, busulphan, cytomegalovirus infection, hematological malignancy, and acute graft versus-host disease (aGVHD). With four risk factors, the risk of HC development was 31%. Risk factors for severe HC of grades 3-5 were aGVHD and bacteremia. PMID- 17845643 TI - Revascularization of trachea in lung and tracheal transplantation. AB - Ischemia is the primary risk factor for airway complications in double lung transplantation using tracheal anastomosis and in tracheal transplantation. Many treatment options as to revascularization for the trachea were herein described and reviewed. They include direct revascularization (using a conduit such as artery or vein), revascularization with tissue wrapping (using omentum, muscle, internal thoracic artery pedicle, pleura, or pericardial fat pad), and with drug administration (using corticosteroid hormone, prostaglandin, or angiogenic factor). As there are few organized reports including new information on revascularization for the trachea these days, this review article would help thoracic surgeons who get engaged transplantation. PMID- 17845644 TI - The use of sirolimus in ganciclovir-resistant cytomegalovirus infections in renal transplant recipients. AB - BACKGROUND: The widespread use of prophylactic ganciclovir and anti lymphocyte/thymocyte therapies are associated with increased induction of ganciclovir-resistant cytomegalovirus (CMV) strains. The use of sirolimus has been associated with a lower incidence of CMV infection in transplant recipients. We questioned whether it could also be effective as a therapeutic treatment of resistant CMV infection. METHODS: Patients with ganciclovir-resistant CMV infections determined clinically and by DNA sequencing analysis were enrolled. Antigenaemia and DNA sequencing were used to diagnosis and follow the mutations. RESULTS: Nine transplant patients were given sirolimus plus mycophenolate mofetil (n = 4) or a calcineurin inhibitor (n = 5). Seven out of nine recipients were CMV IgG negative before transplantation. We observed a rapid decrease in antigenaemia levels, reaching zero in eight out of nine (88.9%) patients within a median of 20.3 +/- 10.1 d. Graft function remained stable and no patient presented acute rejection or recurrence of the CMV infection. CONCLUSIONS: This suggests that the use of sirolimus plus ganciclovir therapy could be useful in ganciclovir resistant CMV infections. PMID- 17845645 TI - It has always been fashionable to attack current medical practice. PMID- 17845646 TI - Intubation training in the real world: a defence of the Northwick Park drill. PMID- 17845647 TI - Continuous cardiac output measurement: arterial pressure analysis versus thermodilution technique during cardiac surgery with cardiopulmonary bypass. AB - This study compared cardiac output measured with an arterial pressure-based cardiac output measurement system and a thermodilution cardiac output measurement system. We studied 36 patients undergoing cardiac surgery with cardiopulmonary bypass. Simultaneous arterial pressure-based and thermodilution cardiac output measurements were compared before and after cardiopulmonary bypass, and after phenylephrine administration. Bland-Altman analysis showed good overall agreement between the two methods. Bias (limits of agreement) before and after cardiopulmonary bypass were - 0.21 (- 2.97-2.55) lxmin(-1) and 0.01 (- 3.79-3.81) lxmin(-1), respectively. Phenylephrine administration decreased thermodilution cardiac output by a mean (SD) of 11 (16)% and increased arterial pressure-based cardiac output by 55 (34)%. We conclude that arterial pressure-based cardiac output and thermodilution cardiac output measurement systems yield comparable results during cardiac surgery with cardiopulmonary bypass. However, after phenylephrine administration, the two measurement systems provided opposing results. PMID- 17845648 TI - Airway topicalisation in morbidly obese patients using atomised lidocaine: 2% compared with 4%. AB - We evaluated the technique of airway anaesthesia using atomised lidocaine for awake oral fibreoptic intubation in morbidly obese patients using two doses of local anaesthetic. Morbidly obese patients were allocated to receive either 2% or 4% lidocaine (40 ml) for oral airway anaesthesia using an atomiser with high oxygen flow. Patients were carefully sedated using midazolam and fentanyl. Outcomes included patient tolerance to airway manipulation, haemodynamic parameters, and serial plasma lidocaine concentrations. In all, 27 patients were enrolled in the study (2% cohort n = 14, 4% cohort n = 13). Patient characteristics and time for topicalisation and airway management were similar. Haemodynamic parameters did not change significantly. Tolerance to insertion of the Ovassapian airway, bronchoscopy, and tracheal tube positioning was excellent (12 vs 12 patients, 12 vs 12 patients, and 8 vs 12 patients had no response, respectively, 2% vs 4%). Differences did not reach statistical significance. Peak plasma lidocaine concentration was significantly lower in the 2% group (2.8 (0.8) microg.ml(-1) compared with 6.5 (1.0) microg.ml(-1), p < 0.05). Airway anaesthesia using atomised lidocaine for awake fibreoptic intubation in the morbidly obese is efficacious, rapid, and safe. Compared with 4% lidocaine, the 2% dose provides acceptable intubating conditions in most cases and produces lower plasma lidocaine levels. PMID- 17845649 TI - The assessment of postoperative pain by monitoring skin conductance: results of a prospective study. AB - The number of fluctuations of skin conductance per second correlates with postoperative pain. The aim of this prospective study was to test the cut-off value for the number of fluctuations of skin conductance per second obtained from a previous study. Seventy-five patients were asked to quantify their level of pain on a numeric rating scale (0-10) in the recovery room. The number of fluctuations of skin conductance per second was recorded simultaneously. The number of fluctuations of skin conductance per second was different between patients with no (0.07), mild (0.16), moderate (0.28) and severe pain (0.33); p < 0.001. The tested cut-off value for the number of fluctuations of skin conductance per second (0.1) distinguished a numeric rating scale 3 with 88.5% sensitivity and 67.7% specificity. The number of fluctuations of skin conductance per second may be a useful means of assessing postoperative pain. PMID- 17845650 TI - Epidural infusion of levobupivacaine and sufentanil following thoracotomy. AB - A prospective, randomised, double-blind study was conducted to compare the efficacy of two doses of levobupivacaine combined with sufentanil for continuous epidural infusion following thoractomy. A total of 72 patients undergoing lobectomy or pneumonectomy were enrolled. An epidural catheter was inserted between the levels of T4 and T6 before induction of anaesthesia and a loading dose of levobupivacaine and sufentanil was administered. At the end of surgery an epidural infusion was commenced at 5 mlxh(-1) and continued for 48 h. Patients were randomly allocated to receive either levobupivacaine 0.125% (group A) or 0.0625% (group B) and all patients also received sufentanil (1 microgxml(-1)). Visual analogue pain scores after coughing (VASi) were always higher in group B (p < 0.05); VAS pain scores at rest were higher for the first 4 h and at 16 and 28 h in group B (p < 0.05). Total morphine consumption and requests number was lower in group A (p < 0.05). Better pain relief was achieved using epidural 0.125% levobupivacaine. PMID- 17845651 TI - Effects of albumin 5% and artificial colloids on clot formation in small infants. AB - Albumin is often cited in textbooks as the gold standard for fluid replacement in paediatrics, but in practice artificial colloids are more frequently used. Although one concern with the use of artificial colloids is their intrinsic action on haemostasis, the available data in children are inconclusive for 6% hydroxyethyl starch 130/0.4 (HES) and no data exist for gelatine solution with respect to coagulation. A total of 42 children (3-15 kg) undergoing surgery and needing colloid replacement were randomly assigned to receive 15 mlxkg(-1) of either albumin 5%, 4% modified gelatine solution or 6% hydroxyethyl starch 130/0.4 solution. Standard coagulation tests and modified thrombelastography (ROTEM) were performed. After colloid administration, routine coagulation test results changed significantly and comparably in all groups, although activated partial thromboplastin time values increased more with gelatine and HES. Coagulation time was unchanged in the children who received albumin or gelatine but other activated modified thrombelastography values were significantly impaired in all groups. After gelatine and after albumin the median clot firmness decreased significantly but remained within the normal range. Following HES, coagulation time increased significantly, and clot formation time, alpha angle, clot firmness, and fibrinogen/fibrin polymerisation were significantly more impaired than for albumin or gelatine, reaching median values below the normal range. From a haemostatic point of view it might be preferable to use gelatine solution as an alternative to albumin; HES showed the greatest effects on the overall coagulation process. PMID- 17845652 TI - The pharmacokinetics of ropivacaine after four different techniques of brachial plexus blockade. AB - Arterial plasma concentrations of ropivacaine were measured after brachial plexus blockade using four different approaches: lateral interscalene (Winnie), posterior interscalene (Pippa), axillary and vertical infraclavicular. Four groups of 10 patients were given a single 3.75 mg.kg(-1) injection of ropivacaine 7.5 mgxml(-1). The pharmacokinetics of ropivacaine were evaluated for 1 h after local anaesthetic injection. The supraclavicular techniques (lateral and posterior) were associated with earlier and higher peak plasma concentrations of local anaesthetic than the infraclavicular techniques (axillary and vertical infraclavicular): mean (SD) values = 3.30 (0.65) microgxml(-1) vs 2.55 (0.62) microgxml(-1) (p = 0.001) in 13.4 (6.9) min vs 25.0 (10.8) min (p = 0.0002). More ropivacaine is taken up by the systemic circulation in the first hour after the supraclavicular approaches; the mean (SD) area under the concentration-time curve was larger: 2.63 (0.51) microgxml(-1).h vs 2.10 (0.49) microgxml(-1).h (p = 0.002). These results show that the technique used for brachial plexus blockade significantly influences the systemic uptake of ropivacaine. PMID- 17845653 TI - Statistics-based alarms from sequential physiological measurements. AB - We have developed an anaesthesia alarm system that responds in a more clinically appropriate manner than current threshold alarms. A decrease in systolic arterial pressure of 10 mmHg from a previous value of 70 mmHg has a greater clinical significance than a decrease of 10 mmHg from 150 mmHg. However, it has been difficult to envisage a simple algorithm for the detection of these contextually adverse changes in physiological variables. We have processed systolic arterial pressure data to create a mathematically straightforward statistical tool for sampling intervals up to 5 min. Both the blood pressure and the change in blood pressure over a known time interval are plotted on x and y axes with the units in standard deviations. Some 10 824 measurements were obtained at 10-s intervals in 17 patients. The mean (SD) systolic arterial pressure for all observations in our patients was 118 (17.0) mmHg. The mean (SD) change in systolic arterial pressure over 5 min was - 0.35 (15.2) mmHg. Combining the value for the standard deviation of systolic arterial pressure and the standard deviation of the change in systolic arterial pressure using Pythagoras's theorem creates a value in standard deviations for this particular state. Instead of alarms being set in mmHg, they would be set in standard deviations. This technique was developed further using Principal Component Analysis to isolate uncommon deviations from normal, clinically unimportant physiological variations. These clinically unimportant changes occur in a predictable fashion only if the sampling interval is 90 s or less. This new alarm system is asymmetric - a small decrease in systolic arterial pressure from 90 mmHg may, appropriately, set off an alarm but it would require a much larger increase in systolic arterial pressure to do so. PMID- 17845654 TI - Ultrasound-guided training in the performance of brachial plexus block by the posterior approach: an observational study. AB - The application of ultrasonography in guiding and controlling the path of the stimulating needle to the brachial plexus via the posterior approach (Pippa technique) was studied. In 21 ASA physical status 1 and 2 patients, scheduled for surgery of the shoulder or upper arm, needle insertion was monitored by ultrasonography and the interaction between needle, surrounding structures and brachial plexus was followed. During injection, the spread of local anaesthetic was visualised and a prediction of block success was made. One failure was predicted. Complete block was achieved in 20 (95%) patients. One potential complication, puncture of the carotid artery, was prevented using ultrasound. Ultrasound is a useful tool in the training and performance of a neurostimulation guided brachial plexus block by the posterior approach. Ultrasonographic guidance may prevent serious complications associated with this approach to the brachial plexus. PMID- 17845655 TI - Comparison of cricothyroidotomy on manikin vs. simulator: a randomised cross-over study. AB - We compared the time taken to perform cricothyroidotomy on a manikin to that on a medium fidelity simulator, to assess the effect of psychological stress and time pressure on performance. Seventy anaesthetists participated in this randomised cross-over study. Fifty-four (77%) anaesthetists took longer on the simulator, with the mean (SD) time taken to perform the procedure on the manikin and simulator 34 (18) and 48 (11) s, respectively (p < 0.001). Anaesthetists with more experience performed the procedure more quickly on both manikin and simulator. We conclude that psychological stress and time pressure in real-life scenarios can affect the performance of cricothyroidotomy. PMID- 17845656 TI - The representation of anaesthesia in children's literature. AB - Hospital admission for an operation can be a frightening and bewildering experience for a child. Effective communication is a prerequisite for all those who anaesthetise children, and good pre-operative preparation reduces anxiety and improves the child's ability to cope. Books are familiar to children and their use in providing information is an established practice in paediatric nursing. By searching web-based bookshops, we identified 19 books whose subject was admission to hospital for an operation. These books were analysed according to the accuracy of their description of the anaesthetic element of the surgical experience. Seven of these books can be recommended as useful descriptions of the key elements involved in general anaesthesia. These books provide a simple, effective and cheap resource to help children and their parents prepare for anaesthesia. They may also provide a useful tool for trainee anaesthetists by giving an insight into the child's level of understanding. PMID- 17845657 TI - Interpleural block - part 1. AB - Interpleural blockade is effective in treating unilateral surgical and nonsurgical pain from the chest and upper abdomen in both the acute and chronic settings. It has been shown to provide safe, high-quality analgesia after cholecystectomy, thoracotomy, renal and breast surgery, and for certain invasive radiological procedures of the renal and hepatobiliary systems. It has also been used successfully in the treatment of pain from multiple rib fractures, herpes zoster, complex regional pain syndromes, thoracic and abdominal cancer, and pancreatitis. The technique is simple to learn and has both few contra indications and a low incidence of complications. In the first of two reviews, the authors cover the history, taxonomy and anatomical considerations, the spread of local anaesthetic, and the mechanism of action, physiological, pharmacological and technical considerations in the performance of the block. PMID- 17845658 TI - Cervical spine movement during laryngoscopy using the Airway Scope compared with the Macintosh laryngoscope. AB - The Airway Scope is a new rigid laryngoscope. This intubation device provides a non-line-of sight view of the glottis. A non-line-of sight view is expected to cause less movement of the cervical spine during laryngeal visualisation. We compared the degree of cervical spine movement during laryngoscopy with the Airway Scope and conventional direct laryngoscope. Twenty patients requiring general anaesthesia and tracheal intubation were studied. Movements of the cervical spine were measured using radiography in the same patient during laryngoscopy with the Airway Scope and a Macintosh laryngoscope. Cervical spine movement during laryngoscopy with the Airway Scope was 37%, 37% and 68% less than that with the Macintosh laryngoscope at the C0/C1, C1/C2 and C3/C4 motion segments, respectively (p < 0.05). The movement of the atlanto-occipital distance using the Airway Scope was 42% less than that during laryngoscopy using the Macintosh laryngoscope (p < 0.05). Laryngoscopy using the Airway Scope involves less movement of the cervical spine compared to conventional laryngoscopy using the Macintosh laryngoscope. PMID- 17845659 TI - User satisfaction and forces generated during laryngoscopy using disposable Miller blades: a manikin study. AB - Increasing awareness of prion-related diseases has led to an increase in the number of disposable laryngoscope blades available. We compared 11 disposable and standard re-usable Miller size 1 blades. In this manikin-based study, we studied user satisfaction for field of view at laryngoscopy, build quality and users' willingness to use the blade in an emergency situation. These were found to be better with metal disposable blades (p or =80 cm in women and > or =90 cm in men. RESULTS: The proportion of subjects in each BMI group was 68.9%, 28.7% and 2.4% for BMI <25, 25-30 and >30, respectively. The prevalence of abdominal obesity was 24.2%. The prevalence of reflux symptoms was 8.2%. Neither BMI nor abdominal obesity was significantly associated with reflux symptoms after adjustment. The prevalence of erosive esophagitis was 6.6%. There was a clear dose-response relationship between prevalence of erosive esophagitis and BMI (5.6%, 8.1% and 15.5% for BMI <25, 25-30 and >30, respectively, P = 0.002). Abdominal obesity was also associated with erosive esophagitis (odds ratio, 2.3; 95% confidence interval, 1.6-3.1). However, only the association between abdominal obesity and erosive esophagitis remained strong after adjustments. CONCLUSIONS: Abdominal obesity rather than BMI is an independent risk factor for erosive esophagitis in the Korean population. PMID- 17845695 TI - Careful patient selection may improve response rates to infliximab in inflammatory bowel disease. AB - BACKGROUND AND AIM: The use of infliximab in the treatment of Crohn's disease (CD) is acceptable and appears to be effective in ulcerative colitis (UC). Careful patient selection, resulting in infliximab only for truly refractory inflammatory bowel disease (IBD), may improve its efficacy. The present study aimed to determine if careful patient selection improved infliximab efficacy in IBD. METHODS: CD or UC/IBD unclassified patients (Montreal classification) were considered for infliximab treatment only after failure of disease control with conventional therapies and confirmation of active disease. Patients with purely luminal IBD received a single infliximab dose. Patients with fistulizing disease (with or without luminal disease) received infliximab at 0, 2 and 6 weeks. Changes to Harvey Bradshaw (HBI) for inflammatory CD and Colitis Activity Index (CAI) for UC/IBDU were used to determine the response and remission rates. In fistulizing CD, a remission was sustained cessation of drainage and resolution of the fistula. Response was correlated to inflammatory marker levels. RESULTS: Seventy IBD patients were treated. In CD, 85.2% (46/54) had active luminal and 40.7% (22/54) had fistulizing disease. In luminal CD, at 8 weeks a single infliximab dose induced remission in 75% (24/32) of patients compared to 92.9% (13/14) after infliximab at 0, 2 and 6 weeks. Fistulizing disease responded in 77.2% (17/22) and remitted in 50% (11/22) of patients at 8 weeks. In UC/IBDU, 75% (12/16) responded and 43.8% (7/16) of patients were in remission at 8 weeks. CONCLUSION: Careful patient selection may improve infliximab's efficacy and clinical remission appears greater after induction with three infliximab doses in CD. Clinical efficacy is suggested for UC/IBDU. PMID- 17845696 TI - Education and imaging. Gastrointestinal: gastric Crohn's disease. PMID- 17845697 TI - Education and imaging. Hepatobiliary and pancreatic: hemosuccus pancreaticus complicating calcific chronic pancreatitis. PMID- 17845698 TI - Education and imaging. Gastrointestinal: infantile hypertrophic pyloric stenosis. PMID- 17845699 TI - Education and imaging. Hepatobiliary and pancreatic: multifocal nodular hepatic steatosis associated with the metabolic syndrome. PMID- 17845700 TI - Education and imaging. Gastrointestinal: obturator hernia. PMID- 17845701 TI - Hepatic infarction during pregnancy in catastrophic antiphospholipid syndrome. PMID- 17845703 TI - A novel approach to simulate segregation at the centreline of continuously cast steel using laser-scanning confocal microscopy. AB - A concentric solidification technique was employed to simulate the segregation of alloying elements that occur during solidification at the centreline of continuously cast steel. Microstructural development of low carbon steel upon solidification has been observed in situ in a laser-scanning confocal microscope. Sulphide precipitates that formed in the last remaining liquid were identified, and evidence is provided that segregation occurring at the centreline of steel slabs can reasonably be simulated by the use of the concentric solidification technique. PMID- 17845704 TI - TEM characterization of precipitates in the segregated regions of a low-carbon, low-manganese, titanium-added steel. AB - A concentric solidification technique has been employed to simulate sulphide precipitation at the centreline of a continuously cast low-carbon, low-manganese, titanium-added steel slab. Selected precipitates were identified using transmission electron microscopy following sample preparation by focused ion beam milling techniques. FeTiS(2) and hexagonal MnS containing iron atoms form in close proximity to each other in super-saturated areas of the concentrically solidified sample. The presence of FeTiS(2) precipitates in low-carbon steel has been verified for the first time, and the crystal structure determined by electron diffraction analysis as a trigonal CdI(2)-type with a P3 m1 space group and lattice parameters of a= 0.341 nm and c= 0.569 nm. PMID- 17845705 TI - Cryo-fluorescence microscopy facilitates correlations between light and cryo electron microscopy and reduces the rate of photobleaching. AB - Fluorescence light microscopy (LM) has many advantages for the study of cell organization. Specimen preparation is easy and relatively inexpensive, and the use of appropriate tags gives scientists the ability to visualize specific proteins of interest. LM is, however, limited in resolution, so when one is interested in ultrastructure, one must turn to electron microscopy (EM), even though this method presents problems of its own. The biggest difficulty with cellular EM is its limited utility in localizing macromolecules of interest while retaining good structural preservation. We have built a cryo-light microscope stage that allows us to generate LM images of vitreous samples prepared for cryo EM. Correlative LM and EM allows one to find areas of particular interest by using fluorescent proteins or vital dyes as markers within vitrified samples. Once located, the sample can be placed in the EM for further study at higher resolution. An additional benefit of the cryo-LM stage is that photobleaching is slower at cryogenic temperatures (-140 degrees C) than at room temperature. PMID- 17845706 TI - Surface structure of size exclusion chromatography stationary phase. AB - Chromatography is a widely used separation unit operation for separating nanomaterials such as proteins and enzymes, quantum dots and carbon nanotubes. An understanding of the chromatographic stationary phase on a nanoscale would be extremely helpful in improving the process and developing efficient and new materials. This study is an attempt to characterize the stationary phase in its swollen wet state using environmental scanning electron microscope (ESEM) and atomic force microscopy (AFM). Observation of the wet beads using ESEM is limited to a micron-range resolution. However, AFM can be used in wet mode to characterize the stationary phase in both wet and dry states with nanometric resolution. In the swollen state, microscale cracks were observed on the surface and this may explain the high mass transfer rate and lower back pressures of the stationary phase. The structures on the surface of the stationary phase depict that the micron-sized beads may be composed of nanometric beads. PMID- 17845707 TI - Quantitative analysis of surface micro-roughness alterations in human spermatozoa using atomic force microscopy. AB - A new male contraceptive given the name RISUG (an acronym for Reversible Inhibition of Sperm Under Guidance) has been developed by our research group. RISUG is a bioactive polymer and is injected into the lumen of the vas deferens using a no-scalpel approach. The polyelectrolytic nature of this contraceptive induces a surface charge imbalance on sperm membrane system leading to its destabilization. Complete disintegration of the plasma membrane with subsequent rupture and dispersion of the acrosomal contents is observed on RISUG treatment. In the present study, micro-structural properties of human spermatozoa exposed to RISUG in vitro have been quantitatively analysed using atomic force microscopy. The parameters used to quantify these morphological changes include amplitude (peak-valley height difference, arithmetic roughness, root mean square roughness) and spatial roughness. Factor loadings (Varimax rotation) have been used to determine the parameters displaying maximum variation. Further, sperm cells have been classified in various principal-component planes using principal-component analysis. The periodic structural features of the atomic force microscopy images have also been obtained using power spectral analysis. PMID- 17845708 TI - A handheld support system to facilitate stereological measurements and mapping of branching structures. AB - BranchSampler is a system for computer-assisted manual stereology written for handheld devices running Windows CE. The system has been designed specifically to streamline data collection and optimize sampling of tree-like branching structures, with particular aims of reducing user errors, saving time, and saving data in formats suited for further analysis in other software, for example, a spreadsheet. The system can be applied in a wide range of applications, from biomedical science to agriculture and horticulture. It can be applied for sampling nested generations of lung bronchioles and renal arterioles or for collection and optimizing sampling of crops for precision agriculture. Although the system has been designed specifically for sampling branching structures, it is sufficiently flexible to be used for other applications involving nested stereological designs. We describe the system specifications, software and Graphical User Interface development, functionality and application of the handheld system using four examples: (a) sampling monkey lung bronchioles for estimation of diameter and wall thickness (b) sampling rat kidney for estimating number of arteries and arterioles in a specific generation (c) mapping fruit (apple) tree yield in an orchard and (d) estimating the total leaf surface area of chrysanthemum plants in a greenhouse. PMID- 17845709 TI - Comparison of quantitative methods for cell-shape analysis. AB - Morphology is an important large-scale manifestation of the global organizational and physiological state of cells, and is commonly used as a qualitative or quantitative measure of the outcome of various assays. Here we evaluate several different basic representations of cell shape - binary masks, distance maps and polygonal outlines - and different subsequent encodings of those representations Fourier and Zernike decompositions, and the principal and independent components analyses - to determine which are best at capturing biologically important shape variation. We find that principal components analysis of two-dimensional shapes represented as outlines provide measures of morphology which are quantitative, biologically meaningful, human interpretable and work well across a range of cell types and parameter settings. PMID- 17845710 TI - Electron precession microdiffraction as a useful tool for the identification of the space group. AB - The possible space groups of a crystal can be identified from a few zone axis microdiffraction patterns provided the position (and not the intensity) of the reflections on the patterns is taken into account. The method is based on the observation of the shifts and the periodicity differences between the reflections located in the first-order Laue zone (FOLZ) with respect to the ones located in the zero-order Laue zone (ZOLZ). Electron precession microdiffraction patterns display more reflections in the ZOLZ and in the FOLZ than in the conventional microdiffraction patterns and this number increases with the precession angle. It is shown, from the TiAl example given in the present study, that this interesting feature brings a strong beneficial effect for the identification of the possible space groups since it becomes very easy to identify unambiguously the FOLZ/ZOLZ shifts and periodicity differences. In addition, the diffracted intensity on the precession patterns is the integrated intensity and this intensity can also be used to identify the Laue class. PMID- 17845711 TI - Topology of the mammalian cell via cryo-FIB etching. AB - Mapping of a mammalian cell down to a feature size of 20-30 nm in 3D is a goal that will answer many questions concerning the connectivity (topology) of a Eukaryotic cell's traffic routes. These routes are defined and separated from one another by the protein-impregnated lipid membrane barrier of the endoplasmic reticulum (ER). We trace the routes from outside a live flash frozen buccal epithelial cell via gold (Au) labelled pores in the plasma membrane to the ER below and then through the cell as isosurfaces in 3D maps. The outer tubular ER with three-way branching changes to a sheet-like ER nearer the nucleus, and the cytoplasmic space between the ER membranes continues as a volume into the nuclear interior via the nuclear pores. We find some evidence that the last layer of the cytoplasmic ER membrane, also termed the outer nuclear membrane, has discrete gaps, so the ER lumen in these areas is continuous with the nuclear luminal domain and further, the inner nuclear membrane has small protrusions into the nucleus. The routes were established in live, unstained, unfixed, cells etched with a pAmp current of a focused ion beam (cryo-FIB) dual beam electron microscope, at -150 degrees C, 1e-4Pa, and confirmed at 37 degrees C in lipid-dye stained cells. The cryo-FIB etch of a cuboid of 2D planes, and its reconstruction into many 3D maps, takes only hours, facilitating the execution of experiments with comparative conditions in a few days. PMID- 17845712 TI - Oblique incidence reflection imaging of live cells: improving contrast and image quality with an objective mask. AB - Dry 40x and 60x microscope objectives were fitted with opaque black masks in order to eliminate reflection and scattering of light off the objective front lens assembly during oblique incidence reflection (OIR) microscopy. The reflection and scattering are shown to induce background glare that leads to degradation in the quality of the OIR images. Mask prototypes were designed and machined to snap onto the spring-loaded retractable front lens assembly of each objective. OIR images of live cells and normalized intensity line profiles are used to demonstrate that, if these alterations to the housing of the objective are implemented, background glare is significantly reduced with the 60x objective, and virtually eliminated with the 40x objective. PMID- 17845713 TI - Association of the microsatellite in the 3' untranslated region of the CD154 gene with rheumatoid arthritis in females from a Spanish cohort: a case-control study. AB - CD40-CD154 interaction is an important mediator of inflammation and has been implicated in T helper type 1-mediated autoimmune diseases including rheumatoid arthritis (RA). Linkage studies have shown association of markers in the proximity of the CD154 gene. In the present work we investigated whether specific allele variants of the microsatellite in the 3' UTR of the CD154 gene might modulate the risk of RA. The study, in a case-control setting, included 189 patients and 150 healthy controls from the Canary Islands, Spain. The 24CAs allele was less represented in female patients than in controls (0.444 in controls versus 0.307 in patients, P = 0.006, odds ratio (OR) 0.556, 95% confidence interval (CI) 0.372 to 0.831) but not in males (0.414 versus 0.408), and only when homozygous (P = 0.012; OR 0.35, 95% CI 0.16 to 0.77). We also verified that CD154 association with RA was independent of human leukocyte antigen (HLA) phenotype. A further functional study showed that after stimulation anti-CD3, CD154 mRNA was more stable in CD4+ T lymphocytes from patients with RA bearing the 24CAs allele (mRNA half-life 208 minutes) than in patients without the 24CAs allele (109 minutes, P = 0.009). However, a lower percentage of CD154+CD4+ T lymphocytes was seen in freshly isolated peripheral blood mononuclear cells from patients carrying 24CAs alleles (mean 4.28 versus 8.12; P = 0.033), and also in CD4+ T lymphocytes stimulated with anti-CD3 (median 29.40 versus 47.60; P = 0.025). These results were concordant with the smaller amounts of CD154 mRNA isolated from stimulated T lymphocytes with 24CAs alleles. The CD154 microsatellite therefore seems to affect the expression of the gene in a complex manner that implies not only mRNA stability. These data suggest that the CD154 microsatellite contributes to the regulation of mRNA and protein expression, although further studies will be necessary to elucidate its role in disease predisposition. PMID- 17845714 TI - Dynamic expression of ancient and novel molluscan shell genes during ecological transitions. AB - BACKGROUND: The Mollusca constitute one of the most morphologically and ecologically diverse metazoan phyla, occupying a wide range of marine, terrestrial and freshwater habitats. The evolutionary success of the molluscs can in part be attributed to the evolvability of the external shell. Typically, the shell first forms during embryonic and larval development, changing dramatically in shape, colour and mineralogical composition as development and maturation proceeds. Major developmental transitions in shell morphology often correlate with ecological transitions (e.g. from a planktonic to benthic existence at metamorphosis). While the genes involved in molluscan biomineralisation are beginning to be identified, there is little understanding of how these are developmentally regulated, or if the same genes are operational at different stages of the mollusc's life. RESULTS: Here we relate the developmental expression of nine genes in the tissue responsible for shell production - the mantle - to ecological transitions that occur during the lifetime of the tropical abalone Haliotis asinina (Vetigastropoda). Four of these genes encode evolutionarily ancient proteins, while four others encode secreted proteins with little or no identity to known proteins. Another gene has been previously described from the mantle of another haliotid vetigastropod. All nine genes display dynamic spatial and temporal expression profiles within the larval shell field and juvenile mantle. CONCLUSION: These expression data reflect the regulatory complexity that underlies molluscan shell construction from larval stages to adulthood, and serves to highlight the different ecological demands placed on each stage. The use of both ancient and novel genes in all stages of shell construction also suggest that a core set of shell-making genes was provided by a shared metazoan ancestor, which has been elaborated upon to produce the range of molluscan shell types we see today. PMID- 17845715 TI - Coverage and error models of protein-protein interaction data by directed graph analysis. AB - Using a directed graph model for bait to prey systems and a multinomial error model, we assessed the error statistics in all published large-scale datasets for Saccharomyces cerevisiae and characterized them by three traits: the set of tested interactions, artifacts that lead to false-positive or false-negative observations, and estimates of the stochastic error rates that affect the data. These traits provide a prerequisite for the estimation of the protein interactome and its modules. PMID- 17845716 TI - How to evaluate the microcirculation: report of a round table conference. AB - INTRODUCTION: Microvascular alterations may play an important role in the development of organ failure in critically ill patients and especially in sepsis. Recent advances in technology have allowed visualization of the microcirculation, but several scoring systems have been used so it is sometimes difficult to compare studies. This paper reports the results of a round table conference that was organized in Amsterdam in November 2006 in order to achieve consensus on image acquisition and analysis. METHODS: The participants convened to discuss the various aspects of image acquisition and the different scores, and a consensus statement was drafted using the Delphi methodology. RESULTS: The participants identified the following five key points for optimal image acquisition: five sites per organ, avoidance of pressure artifacts, elimination of secretions, adequate focus and contrast adjustment, and recording quality. The scores that can be used to describe numerically the microcirculatory images consist of the following: a measure of vessel density (total and perfused vessel density; two indices of perfusion of the vessels (proportion of perfused vessels and microcirculatory flow index); and a heterogeneity index. In addition, this information should be provided for all vessels and for small vessels (mostly capillaries) identified as smaller than 20 microm. Venular perfusion should be reported as a quality control index, because venules should always be perfused in the absence of pressure artifact. It is anticipated that although this information is currently obtained manually, it is likely that image analysis software will ease analysis in the future. CONCLUSION: We proposed that scoring of the microcirculation should include an index of vascular density, assessment of capillary perfusion and a heterogeneity index. PMID- 17845717 TI - Comparison of Bayesian and frequentist approaches in modelling risk of preterm birth near the Sydney Tar Ponds, Nova Scotia, Canada. AB - BACKGROUND: This study compares the Bayesian and frequentist (non-Bayesian) approaches in the modelling of the association between the risk of preterm birth and maternal proximity to hazardous waste and pollution from the Sydney Tar Pond site in Nova Scotia, Canada. METHODS: The data includes 1604 observed cases of preterm birth out of a total population of 17559 at risk of preterm birth from 144 enumeration districts in the Cape Breton Regional Municipality. Other covariates include the distance from the Tar Pond; the rate of unemployment to population; the proportion of persons who are separated, divorced or widowed; the proportion of persons who have no high school diploma; the proportion of persons living alone; the proportion of single parent families and average income. Bayesian hierarchical Poisson regression, quasi-likelihood Poisson regression and weighted linear regression models were fitted to the data. RESULTS: The results of the analyses were compared together with their limitations. CONCLUSION: The results of the weighted linear regression and the quasi-likelihood Poisson regression agrees with the result from the Bayesian hierarchical modelling which incorporates the spatial effects. PMID- 17845718 TI - Detection of RNA structures in porcine EST data and related mammals. AB - BACKGROUND: Non-coding RNAs (ncRNAs) are involved in a wide spectrum of regulatory functions. Within recent years, there have been increasing reports of observed polyadenylated ncRNAs and mRNA like ncRNAs in eukaryotes. To investigate this further, we examined the large data set in the Sino-Danish PigEST resource http://pigest.ku.dk which also contains expression information distributed on 97 non-normalized cDNA libraries. RESULTS: We constructed a pipeline, EST2ncRNA, to search for known and novel ncRNAs. The pipeline utilises sequence similarity to ncRNA databases (blast), structure similarity to Rfam (RaveNnA) as well as multiple alignments to predict conserved novel putative RNA structures (RNAz). EST2ncRNA was fed with 48,000 contigs and 73,000 singletons available from the PigEST resource. Using the pipeline we identified known RNA structures in 137 contigs and single reads (conreads), and predicted high confidence RNA structures in non-protein coding regions of additional 1,262 conreads. Of these, structures in 270 conreads overlap with existing predictions in human. To sum up, the PigEST resource comprises trans-acting elements (ncRNAs) in 715 contigs and 340 singletons as well as cis-acting elements (inside UTRs) in 311 contigs and 51 singletons, of which 18 conreads contain both predictions of trans- and cis acting elements. The predicted RNAz candidates were compared with the PigEST expression information and we identify 114 contigs with an RNAz prediction and expression in at least ten of the non-normalised cDNA libraries. We conclude that the contigs with RNAz and known predictions are in general expressed at a much lower level than protein coding transcripts. In addition, we also observe that our ncRNA candidates constitute about one to two percent of the genes expressed in the cDNA libraries. Intriguingly, the cDNA libraries from developmental (brain) tissues contain the highest amount of ncRNA candidates, about two percent. These observations are related to existing knowledge and hypotheses about the role of ncRNAs in higher organisms. Furthermore, about 80% porcine coding transcripts (of 18,600 identified) as well as less than one-third ORF-free transcripts are conserved at least in the closely related bovine genome. Approximately one percent of the coding and 10% of the remaining matches are unique between the PigEST data and cow genome. Based on the pig-cow alignments, we searched for similarities to 16 other organisms by UCSC available alignments, which resulted in a 87% coverage by the human genome for instance. CONCLUSION: Besides recovering several of the already annotated functional RNA structures, we predicted a large number of high confidence conserved secondary structures in polyadenylated porcine transcripts. Our observations of relatively low expression levels of predicted ncRNA candidates together with the observations of higher relative amount in cDNA libraries from developmental stages are in agreement with the current paradigm of ncRNA roles in higher organisms and supports the idea of polyadenylated ncRNAs. PMID- 17845719 TI - A systematic comparison of software dedicated to meta-analysis of causal studies. AB - BACKGROUND: Our objective was to systematically assess the differences in features, results, and usability of currently available meta-analysis programs. METHODS: Systematic review of software. We did an extensive search on the internet (Google, Yahoo, Altavista, and MSN) for specialized meta-analysis software. We included six programs in our review: Comprehensive Meta-analysis (CMA), MetAnalysis, MetaWin, MIX, RevMan, and WEasyMA. Two investigators compared the features of the software and their results. Thirty independent researchers evaluated the programs on their usability while analyzing one data set. RESULTS: The programs differed substantially in features, ease-of-use, and price. Although most results from the programs were identical, we did find some minor numerical inconsistencies. CMA and MIX scored highest on usability and these programs also have the most complete set of analytical features. CONCLUSION: In consideration of differences in numerical results, we believe the user community would benefit from openly available and systematically updated information about the procedures and results of each program's validation. The most suitable program for a meta analysis will depend on the user's needs and preferences and this report provides an overview that should be helpful in making a substantiated choice. PMID- 17845720 TI - Effects of ambient air pollution on functional status in patients with chronic congestive heart failure: a repeated-measures study. AB - BACKGROUND: Studies using administrative data report a positive association between ambient air pollution and the risk of hospitalization for congestive heart failure (HF). Circulating levels of B-type natriuretic peptide (BNP) are directly associated with cardiac hemodynamics and symptom severity in patients with HF and, therefore, serves as a marker of functional status. We tested the hypothesis that BNP levels would be positively associated with short-term changes in ambient pollution levels among 28 patients with chronic stable HF and impaired systolic function. METHODS: BNP was measured in whole blood at 0, 6, and 12 weeks. We used linear mixed models to evaluate the association between fine particulate matter (PM2.5), carbon monoxide, sulfur dioxide, nitrogen dioxide, ozone, and black carbon and log(BNP). Lags of 0 to 3 days were considered in separate models. We calculated the intraclass correlation coefficient and within subject coefficient of variation as measures of reproducibility. RESULTS: We found no association between any pollutant and measures of BNP at any lag. For example, a 10 microg/m3 increase in PM2.5 was associated with a 0.8% (95% CI: 16.4, 21.5; p = 0.94) increase in BNP on the same day. The within-subject coefficient of variation was 45% on the natural scale and 9% on the log scale. CONCLUSION: These results suggest that serial BNP measurements are unlikely to be useful in a longitudinal study of air pollution-related acute health effects. The magnitude of expected ambient air pollution health effects appears small in relation to the considerable within-person variability in BNP levels in this population. PMID- 17845721 TI - Role of human HGFIN/nmb in breast cancer. AB - INTRODUCTION: HGFIN, previously identified as nmb, and its homolog osteoactivin are single transmembrane proteins that are expressed in differentiated immune cells. These proteins exhibit properties that could potentiate tumorigenesis or decrease invasiveness. These seemingly opposing roles of HGFIN suggest that this protein might be central to malignancies and might also behave as a tumor suppressor. Consistent with the reported roles for HGFIN is the fact that this gene is regulated by p53 through multiple binding sites in the 5' flanking region, and is expressed in osteoblasts. METHODS: This study used siRNA to knock out HGFIN in non-tumorigenic breast cells and ectopically expressed HGFIN in breast cancer cells. In addition, in situ hybridization studies analyzed primary breast tissues from archived breast surgeries. Reporter gene assays studied the untranslated exon 1 of HGFIN. RESULTS: HGFIN expression led to reduced cell growth of breast cancer cells and reduced migration. At the molecular level, reporter gene analyses determined the untranslated exon 1 to be a negative regulator of the upstream enhancing effect. Ectopic expression of wild-type p53 in breast cancer cells that expressed endogenous mutant p53 resulted in increased HGFIN reporter gene activities. CONCLUSION: As the majority of cancer cells have mutations in p53, further studies on the relationship between p53 and HGFIN expression, and its role in tumor genesis and bone invasion, might uncover novel therapy targets for breast and other cancers. The results show a central role for p53 in HGFIN expression, which appears to determine the behavior of the cancer cells. PMID- 17845722 TI - The LeFE algorithm: embracing the complexity of gene expression in the interpretation of microarray data. AB - Interpretation of microarray data remains a challenge, and most methods fail to consider the complex, nonlinear regulation of gene expression. To address that limitation, we introduce Learner of Functional Enrichment (LeFE), a statistical/machine learning algorithm based on Random Forest, and demonstrate it on several diverse datasets: smoker/never smoker, breast cancer classification, and cancer drug sensitivity. We also compare it with previously published algorithms, including Gene Set Enrichment Analysis. LeFE regularly identifies statistically significant functional themes consistent with known biology. PMID- 17845723 TI - Axon and dendrite geography predict the specificity of synaptic connections in a functioning spinal cord network. AB - BACKGROUND: How specific are the synaptic connections formed as neuronal networks develop and can simple rules account for the formation of functioning circuits? These questions are assessed in the spinal circuits controlling swimming in hatchling frog tadpoles. This is possible because detailed information is now available on the identity and synaptic connections of the main types of neuron. RESULTS: The probabilities of synapses between 7 types of identified spinal neuron were measured directly by making electrical recordings from 500 pairs of neurons. For the same neuron types, the dorso-ventral distributions of axons and dendrites were measured and then used to calculate the probabilities that axons would encounter particular dendrites and so potentially form synaptic connections. Surprisingly, synapses were found between all types of neuron but contact probabilities could be predicted simply by the anatomical overlap of their axons and dendrites. These results suggested that synapse formation may not require axons to recognise specific, correct dendrites. To test the plausibility of simpler hypotheses, we first made computational models that were able to generate longitudinal axon growth paths and reproduce the axon distribution patterns and synaptic contact probabilities found in the spinal cord. To test if probabilistic rules could produce functioning spinal networks, we then made realistic computational models of spinal cord neurons, giving them established cell-specific properties and connecting them into networks using the contact probabilities we had determined. A majority of these networks produced robust swimming activity. CONCLUSION: Simple factors such as morphogen gradients controlling dorso-ventral soma, dendrite and axon positions may sufficiently constrain the synaptic connections made between different types of neuron as the spinal cord first develops and allow functional networks to form. Our analysis implies that detailed cellular recognition between spinal neuron types may not be necessary for the reliable formation of functional networks to generate early behaviour like swimming. PMID- 17845724 TI - Comparative phylogenomic analyses of teleost fish Hox gene clusters: lessons from the cichlid fish Astatotilapia burtoni. AB - BACKGROUND: Teleost fish have seven paralogous clusters of Hox genes stemming from two complete genome duplications early in vertebrate evolution, and an additional genome duplication during the evolution of ray-finned fish, followed by the secondary loss of one cluster. Gene duplications on the one hand, and the evolution of regulatory sequences on the other, are thought to be among the most important mechanisms for the evolution of new gene functions. Cichlid fish, the largest family of vertebrates with about 2500 species, are famous examples of speciation and morphological diversity. Since this diversity could be based on regulatory changes, we chose to study the coding as well as putative regulatory regions of their Hox clusters within a comparative genomic framework. RESULTS: We sequenced and characterized all seven Hox clusters of Astatotilapia burtoni, a haplochromine cichlid fish. Comparative analyses with data from other teleost fish such as zebrafish, two species of pufferfish, stickleback and medaka were performed. We traced losses of genes and microRNAs of Hox clusters, the medaka lineage seems to have lost more microRNAs than the other fish lineages. We found that each teleost genome studied so far has a unique set of Hox genes. The hoxb7a gene was lost independently several times during teleost evolution, the most recent event being within the radiation of East African cichlid fish. The conserved non-coding sequences (CNS) encompass a surprisingly large part of the clusters, especially in the HoxAa, HoxCa, and HoxDa clusters. Across all clusters, we observe a trend towards an increased content of CNS towards the anterior end. CONCLUSION: The gene content of Hox clusters in teleost fishes is more variable than expected, with each species studied so far having a different set. Although the highest loss rate of Hox genes occurred immediately after whole genome duplications, our analyses showed that gene loss continued and is still ongoing in all teleost lineages. Along with the gene content, the CNS content also varies across clusters. The excess of CNS at the anterior end of clusters could imply a stronger conservation of anterior expression patters than those towards more posterior areas of the embryo. PMID- 17845725 TI - New active site oriented glyoxyl-agarose derivatives of Escherichia coli penicillin G acylase. AB - BACKGROUND: Immobilized Penicillin G Acylase (PGA) derivatives are biocatalysts that are industrially used for the hydrolysis of Penicillin G by fermentation and for the kinetically controlled synthesis of semi-synthetic beta-lactam antibiotics. One of the most used supports for immobilization is glyoxyl activated agarose, which binds the protein by reacting through its superficial Lys residues. Since in E. coli PGA Lys are also present near the active site, an immobilization that occurs through these residues may negatively affect the performance of the biocatalyst due to the difficult diffusion of the substrate into the active site. A preferential orientation of the enzyme with the active site far from the support surface would be desirable to avoid this problem. RESULTS: Here we report how it is possible to induce a preferential orientation of the protein during the binding process on aldehyde activated supports. A superficial region of PGA, which is located on the opposite side of the active site, is enriched in its Lys content. The binding of the enzyme onto the support is consequently forced through the Lys rich region, thus leaving the active site fully accessible to the substrate. Different mutants with an increasing number of Lys have been designed and, when active, immobilized onto glyoxyl agarose. The synthetic performances of these new catalysts were compared with those of the immobilized wild-type (wt) PGA. Our results show that, while the synthetic performance of the wt PGA sensitively decreases after immobilization, the Lys enriched mutants have similar performances to the free enzyme even after immobilization. We also report the observations made with other mutants which were unable to undergo a successful maturation process for the production of active enzymes or which resulted toxic for the host cell. CONCLUSION: The desired orientation of immobilized PGA with the active site freely accessible can be obtained by increasing the density of Lys residues on a predetermined region of the enzyme. The newly designed biocatalysts display improved synthetic performances and are able to maintain a similar activity to the free enzymes. Finally, we found that the activity of the immobilized enzyme proportionally improves with the number of introduced Lys. PMID- 17845726 TI - Ductal carcinoma in situ of the breast (DCIS) with heterogeneity of nuclear grade: prognostic effects of quantitative nuclear assessment. AB - BACKGROUND: Previously, 50% of patients with breast ductal carcinoma in situ (DCIS) had more than one nuclear grade, and neither worst nor predominant nuclear grade was significantly associated with development of invasive carcinoma. Here, we used image analysis in addition to histologic evaluation to determine if quantification of nuclear features could provide additional prognostic information and hence impact prognostic assessments. METHODS: Nuclear image features were extracted from about 200 nuclei of each of 80 patients with DCIS who underwent lumpectomy alone, and received no adjuvant systemic therapy. Nuclear images were obtained from 20 representative nuclei per duct, from each of a group of 5 ducts, in two separate fields, for 10 ducts. Reproducibility of image analysis features was determined, as was the ability of features to discriminate between nuclear grades. Patient information was available about clinical factors (age and method of DCIS detection), pathologic factors (DCIS size, nuclear grade, margin size, and amount of parenchymal involvement), and 39 image features (morphology, densitometry, and texture). The prognostic effects of these factors and features on the development of invasive breast cancer were examined with Cox step-wise multivariate regression. RESULTS: Duplicate measurements were similar for 89.7% to 97.4% of assessed image features. For the pooled assessment with approximately 200 nuclei per patient, a discriminant function with one densitometric and two texture features was significantly (p < 0.001) associated with nuclear grading, and provided 78.8% correct jackknifed classification of a patient's nuclear grade. In multivariate assessments, image analysis nuclear features had significant prognostic associations (p or=2-fold change, 11 of which had CpG island-associated promoters. Interestingly, 6 of these 11 were pro-apoptotic genes and decitabine resulted in a significant induction of cell death in U2OS cells in vitro (p < 0.05). The 6 pro-apoptotic genes (GADD45A, HSPA9B, PAWR, PDCD5, NFKBIA, and TNFAIP3) were also induced to >or=2-fold in vivo. Quantitative methylation pyrosequencing confirmed that the tested pro-apoptotic genes had CpG island DNA demethylationas a result of U2OS decitabine treatment both in vitro and in xenografts. CONCLUSION: These data provide new insights regarding the use of epigenetic modifiers in OS, and have important implications for therapeutic trials involving demethylation drugs. Collectively, these data have provided biological evidence that one mode of action of decitabine may be the induction of apoptosis utilizing promoter-CpG demethylation of specific effectors in cell death pathways in OS. PMID- 17845730 TI - An investigation of the effects of lipid-lowering medications: genome-wide linkage analysis of lipids in the HyperGEN study. AB - BACKGROUND: Use of anti-hyperlipidemic medications compromises genetic analysis because of altered lipid profiles. We propose an empirical method to adjust lipid levels for medication effects so that the adjusted lipid values substitute the unmedicated lipid values in the genetic analysis. RESULTS: Published clinical trials were reviewed for HMG-CoA reductase inhibitors and fibric acid derivatives as mono-drug therapy. HMG-CoA reductase inhibitors showed similar effects in African Americans (AA) and non-African Americans (non-AA) for lowering total cholesterol (TC, -50.7 mg/dl), LDL cholesterol (LDL-C, -48.1 mg/dl), and triglycerides (TG, -19.7 mg/dl). Their effect on increasing HDL cholesterol (HDL C) in AA (+0.4 mg/dl) was lower than in Non-AA (+2.3 mg/dl). The effects of fibric acid derivatives were estimated as -46.1 mg/dl for TC, -40.1 mg/dl for LDL C, and +5.9 mg/dl for HDL-C in non-AA. The corresponding effects in AA were less extreme (-20.1 mg/dl, -11.4 mg/dl, and +3.1 mg/dl). Similar effect for TG (59.0 mg/dl) was shown in AA and non-AA. The above estimated effects were applied to a multipoint variance components linkage analysis on the lipid levels in 2,403 Whites and 2,214 AA in the HyperGEN study. The familial effects did vary depending on whether the lipids were adjusted for medication use. For example, the heritabilities increased after medication adjustment for TC and LDL-C, but did not change significantly for HDL-C and TG. CONCLUSION: Ethnicity-specific medication adjustments using our empirical method can be employed in epidemiological and genetic analysis of lipids. PMID- 17845731 TI - Interrelated modulation of endothelial function in Behcet's disease by clinical activity and corticosteroid treatment. AB - Corticosteroids are commonly used in empirical treatment of Behcet's disease (BD), a systemic inflammatory condition associated with reversible endothelial dysfunction. In the present study we aimed to dissect the effects of clinical disease activity and chronic or short-term corticosteroid treatment on endothelial function in patients with BD. In a case-control, cross-sectional study, we assessed endothelial function by endothelium dependent flow mediated dilatation (FMD) at the brachial artery of 87 patients, who either were or were not receiving chronic corticosteroid treatment, and exhibiting variable clinical disease activity. Healthy individuals matched for age and sex served as controls. Endothelial function was also assessed in a prospective study of 11 patients before and after 7 days of treatment with prednisolone given at disease relapse (20 mg/day). In the cross-sectional component of the study, FMD was lower in patients than in control individuals (mean +/- standard error: 4.1 +/- 0.4% versus 5.7 +/- 0.2%, P = 0.003), whereas there was a significant interaction between the effects of corticosteroids and disease activity on endothelial function (P = 0.014, two-factor analysis of variance). Among patients with inactive BD, those who were not treated with corticosteroids (n = 33) had FMD comparable to that in healthy control individuals, whereas those treated with corticosteroids (n = 15) had impaired endothelial function (P = 0.023 versus the respective control subgroup). In contrast, among patients with active BD, those who were not treated with corticosteroids (n = 20) had lower FMD than control individuals (P = 0.007), but in those who were receiving corticosteroids (n = 19) the FMD values were comparable to those in control individuals. Moreover, FMD was significantly improved after 7 days of prednisolone administration (3.7 +/- 0.9% versus 7.6 +/- 1.4%, P = 0.027). Taken together, these results imply that although corticosteroid treatment may impair endothelial function per se during the remission phase of the inflammatory process, it restores endothelial dysfunction during active BD by counteracting the harmful effects of relapsing inflammation. PMID- 17845733 TI - Musical hallucinations induced by drugs. AB - Dipyridamole is an antiplatelet agent and a vasodilator which is increasingly being used for the secondary prevention of ischaemic stroke and transient ischemic attack, either alone or in combination with acetylsalicylic acid. We describe an 83-year-old woman who had developed musical hallucinations within days of initiating dipyridamole. Her psychiatric and neurological evaluation was otherwise unremarkable. After the discontinuation of dipyridamole the hallucinations ceased within a couple of days. To the best of our knowledge this is the first case of auditory hallucinations associated with dipyridamole reported in the literature. PMID- 17845732 TI - Alternative splicing of TGF-betas and their high-affinity receptors T beta RI, T beta RII and T beta RIII (betaglycan) reveal new variants in human prostatic cells. AB - BACKGROUND: The transforming growth factors (TGF)-beta, TGF-beta1, TGF-beta2 and TGF-beta 3, and their receptors [T beta RI, T beta RII, T beta R III (betaglycan)] elicit pleiotropic functions in the prostate. Although expression of the ligands and receptors have been investigated, the splice variants have never been analyzed. We therefore have analyzed all ligands, the receptors and the splice variants T beta RIB, T beta RIIB and TGF-beta 2B in human prostatic cells. RESULTS: Interestingly, a novel human receptor transcript T beta RIIC was identified, encoding additional 36 amino acids in the extracellular domain, that is expressed in the prostatic cancer cells PC-3, stromal hPCPs, and other human tissues. Furthermore, the receptor variant T beta RIB with four additional amino acids was identified also in human. Expression of the variant T beta RIIB was found in all prostate cell lines studied with a preferential localization in epithelial cells in some human prostatic glands. Similarly, we observed localization of T beta RIIC and TGF-beta 2B mainly in the epithelial cells with a preferential localization of TGF-beta 2B in the apical cell compartment. Whereas in the androgen-independent hPCPs and PC-3 cells all TGF-beta ligands and receptors are expressed, the androgen-dependent LNCaP cells failed to express all ligands. Additionally, stimulation of PC-3 cells with TGF-beta2 resulted in a significant and strong increase in secretion of plasminogen activator inhibitor-1 (PAI-1) with a major participation of T beta RII. CONCLUSION: In general, expression of the splice variants was more heterogeneous in contrast to the well known isoforms. The identification of the splice variants T beta RIB and the novel isoform T beta RIIC in man clearly contributes to the growing complexity of the TGF-beta family. PMID- 17845734 TI - Experimental infection and adaptation of Rodentolepis nana to the Mongolian jird Meriones unguiculatus. AB - A mouse-derived strain of Rodentolepis ( = Hymenolepis) nana was transferred to the Mongolian jird Meriones unguiculatus. It was found that M. unguiculatus has low susceptibility to R. nana mouse isolates. Likewise, adaptation of the parasite to jird hosts, in the absence of dexamethasone treatment, was not demonstrable, at least during ten-passage trials. Nevertheless, the parasite was able to establish, grow and develop to gravid adults in M. unguiculatus treated daily with dexamethasone. Prepatent periods in dexamethasone-treated jirds in ten passage series ranged from 10 to 17 days post-infection (DPI), the average being 12 days, and the patent periods lasted from 18 to 30 DPI, with an average of 25 days. The population pattern of faecal egg output in immunosuppressed jirds suggests that under a daily dexamethasone treatment protocol, the parasite is able to maintain egg production as long as treatment is sustained. PMID- 17845735 TI - Inhibition by soya isoflavones of human polymorphonuclear leukocyte function: possible relevance for the beneficial effects of soya intake. AB - Lower CVD incidence is reported in Asian populations consuming soya-containing food. As polymorphonuclear leukocytes (PMN) are involved in the risk of CVD, we investigated the modulatory effect of soya isoflavones on several PMN functions and their molecular mechanisms in vitro. PMN, isolated from blood from healthy subjects, were tested upon activation with 1 microm- n-formyl-methyl-leucyl phenylalanine (fMLP) for superoxide anion production (ferric cytochrome c reduction) and released elastase (chromogenic test). PMN homotypic aggregates stimulated by fMLP or P-selectin in dynamic conditions were detected by optical microscopy. PMN, mixed with thrombin-activated, washed platelets, formed cell aggregates, measured by flow cytometry. Phosphorylation of Pyk2, a focal adhesion kinase, was studied by immunoprecipitation and immunoblotting with specific antibodies. Genistein, daidzein and equol inhibited superoxide anion production (IC50 0.25 (sem 0.1), 21.0 (sem 4.2) and 13.0 (sem 2.8) microm, respectively); the release of elastase was prevented by genistein (IC50 63 (sem 17) microm). PMN homotypic aggregates, stimulated by fMLP, were significantly reduced (24 (sem 12) and 51 (sem 14) % of control) by 100 microm genistein and equol. P-selectin induced aggregates were reduced to 19 (sem 6), 44 (sem 10) and 28 (sem 9) % of control by 100 microm genistein, daidzein and equol, respectively. Genistein, daidzein and equol also significantly reduced mixed platelet-PMN aggregates (IC50 4.0 (sem 0.9), 57 (sem 6) and 66 (sem 23) microm, respectively). In PMN challenged by fMLP or P-selectin, activation of Pyk2 was prevented by isoflavones. The cardioprotective effect of soya-containing food might be linked to reduction of PMN activation and PMN-platelet interaction, novel targets for the biological effects of soya isoflavones. PMID- 17845736 TI - Precursors and mediators of intergroup reconciliation in Northern Ireland: a new model. AB - We examined social psychological factors contributing to the restoration of the intergroup relationship between Protestants and Catholics in Northern Ireland. A theoretical model of reconciliation orientation (ROM) was developed, with intergroup forgiveness and subjective evaluation of past violence as the main precursors of that orientation. Data from a Northern Irish sample (N=318) validated and extended the model. Forgiveness and evaluation of past violence were predicted by 'competitive victimhood' (a belief in having suffered more than the out-group), negatively and positively, respectively. These associations were fully accounted for by the strength of identification with the in-group and trust in the out-group. Empathy functioned mainly as a direct predictor of forgiveness. The theoretical and practical implications of these results are discussed. PMID- 17845737 TI - Expectancies, not aroma, explain impact of lavender aromatherapy on psychophysiological indices of relaxation in young healthy women. AB - OBJECTIVES: In aromatherapy, lavender aroma is reputed to assist with relaxation. However, while there is much anecdotal evidence to that effect, the empirical literature is very inconsistent. Failure to employ adequate placebos, proper blinding, objective measures, or screening of prior beliefs about aromatherapy means that many previous findings could have been influenced by expectancy biases. The present study sought to establish whether lavender aroma and/or expectancies affect post-stress relaxation. DESIGN: A double-blind, 3 (aroma) x 3 (instruction) x 10 (time in minutes) mixed-factorial placebo-controlled trial. METHOD: In a laboratory, 96 healthy undergraduate women were exposed to lavender, placebo, or no aroma during physiologically assessed relaxation after an arousing cognitive task. Where an aroma was presented, an instructional priming procedure was used to manipulate participants' expectancies about the aroma's likely impact on their ability to relax. RESULTS: Results showed no effect of aroma on galvanic skin response during relaxation. However, the nature of instructional prime was associated with relaxation patterns: when expecting the aroma to inhibit them, participants relaxed more; when expecting facilitation, participants relaxed less. The effect was not seen with regard to self-reported relaxation (as represented by changes in state anxiety) and was independent of ratings of attitudes towards aromatherapy. CONCLUSIONS: The findings imply that the previous associations of lavender aroma with assisted relaxation may have been influenced by expectancy biases, and that the relevant expectancies are easily manipulable. PMID- 17845738 TI - A randomized group intervention trial to enhance mood and self-efficacy in people with multiple sclerosis. AB - OBJECTIVES: To document mood, self-efficacy, and resiliency in people with multiple sclerosis (MS) following a brief group psychological intervention, and to examine whether benefits were greater than those derived from provision of education or group social interaction. DESIGN: A randomized controlled intervention trial assessing outcomes at five time points over a 1-year follow up. METHODS: Participants with MS were assigned to one of three groups: one receiving brief group psychological intervention (PG) comprising three 90 minute cognitive behavioural sessions supported by an Information Booklet dealing with mental and emotional issues relating to MS; a group provided only with educational material - the information booklet group (IBG); and a group who not only received the booklet but also participated in non-structured social discussion (SDG) sessions similar in length and number to PG participants. Outcomes were documented using questionnaires. RESULTS: Outcomes were assessed using area under the curve (AUC) analysis: a summary measure that considers individual changes serially over time to provide a more meaningful picture than the one based on single time points. Ninety participants were followed up over the 12-month post-intervention, and their data are included in the analysis. Analyses indicated benefits in all outcome dimensions for the psychotherapeutic (PG) and social discussion groups (SDG) relative to the IBG group, but no differences between PG and SDG. CONCLUSION: The study indicates benefits from psychosocial intervention compared with bibliotherapy, with some additional benefit from psychological intervention compared with a social discussion group. Results suggest that much of the benefit may derive from non-specific therapeutic components. Without psychosocial intervention, the psychological status of people with MS worsened over time. PMID- 17845739 TI - The roles of perceived task interdependence and group members' interdependence in the development of collective efficacy in university student group contexts. AB - BACKGROUND: Although the relationship between collective efficacy and group performance has been frequently investigated, a few studies have investigated the development of collective efficacy. AIM: This paper proposes some determinants of collective efficacy in small university groups. Group level hypotheses and research questions relating collective efficacy to collective cognition activities, task interdependence, self-efficacy for group work, and collective orientation were posited. SAMPLE: The sample comprised 145 university students in 40 work-groups. METHOD: A two-phase longitudinal design was employed in the context of university student groups. All groups were required to perform interdependent academic tasks. Aggregated variables were used after testing for within-group agreement. RESULTS: The results of multiple regression analysis provided some evidence that the more group members perceived themselves to be interdependent in the early stages of group work and assigned their tasks interdependently during group processes, the more likely they were to develop high collective efficacy in the final stages of group work. Collective efficacy was also related to the group average of self-efficacy for group work especially when task interdependence was perceived to be high. CONCLUSIONS: The results suggest that forming groups with capable university students in group work, strengthening university students' perceptions of themselves as interdependent in the early stages of academic group work and assigning interdependent group tasks during group work may contribute to the development of high collective efficacy. PMID- 17845740 TI - Organization of co-occurring Axis II features in borderline personality disorder. AB - OBJECTIVES: Considerable heterogeneity exists in the comorbid Axis II features that frequently accompany borderline personality disorder (BPD). These features have potential to be meaningfully organized, relate to specific BPD presentation, and have implications for treatment process and outcome. The present study explored patterns of Axis II comorbidity in order to identify subtypes of BPD. DESIGN: A well-defined sample of 90 patients diagnosed with BPD was recruited as part of an RCT study. Participants were administered the International Personality Disorder Examination (Loranger, 1999) to diagnose BPD and assess comorbid Axis II features. Other measures were also administered to assess aspects of current work and relationship functioning, symptomatology, and self concept. METHODS AND RESULTS: Q-factoring was used to develop subtypes based on commonly occurring Axis II profiles, identifying three: Cluster A (elevated paranoid and schizotypal features), Cluster B (elevated narcissistic and histrionic features), and Cluster C (elevated avoidant and obsessive-compulsive features). An additional factor analysis revealed two dimensions underlying the comorbid features identifiable as: extraversion versus introversion and antagonism versus constraint. Validity of these two maps of comorbidity was explored in terms of the BPD criteria themselves, as well as on work and relationship functioning, identity diffusion, views of self and others, positive and negative affect, behavioural dyscontrol, and symptomatic distress. CONCLUSIONS: Clinically meaningful subtypes can be identified for BPD based on co occurring Axis II features. Further research is needed to replicate and further establish base-rates of these subtypes as well as their differential implications for treatment. PMID- 17845741 TI - Compulsive hoarding: a qualitative investigation of partner and carer perspectives. AB - OBJECTIVE: This study explores the experiences of family members caring for a person who compulsively hoards. DESIGN: Ten participants, all 'key carers' for a hoarding family member, were interviewed using a semi-structured interview schedule designed for the purpose of the study. METHODS: Transcribed interviews were analysed using interpretive phenomenological analysis. RESULTS: Five superordinate, discrete but interconnecting themes were identified: 'loss of normal family life'; 'the need for understanding'; 'coping with the situation'; 'impact on relationships'; and 'marginalization'. Carers' accommodation of hoarding behaviours and role isolation were examined in drawing connections between themes. Outlying themes suggesting factors protective of relationships and facilitating coping were also identified. CONCLUSION: Carers struggled to cope with both the environmental and interpersonal impacts of the hoarding. Lacking both formal and informal networks of support, carers are in need of information and treatment options for themselves and their families. Possible avenues for future clinical and theoretical research are suggested. PMID- 17845742 TI - Preventing postoperative nausea and vomiting: post hoc analysis of pooled data from two randomized active-controlled trials of aprepitant. AB - OBJECTIVE: Compared with the 5HT(3) antagonist ondansetron, the NK(1) antagonist aprepitant has been shown in two double-blind trials to provide greater protection against postoperative vomiting and comparable or greater control of nausea. Post hoc analyses of pooled data from these trials were performed to more fully characterize the efficacy profile of aprepitant in terms of nausea and use of rescue therapy. RESEARCH DESIGN AND METHODS: Patients (n = 1599) scheduled for major surgery under general anesthesia (primarily gynecological surgery) were assigned to receive a preoperative dose of aprepitant 40 mg PO, 125 mg PO, or ondansetron 4 mg IV. in two randomized, double-blind, clinical trials. MAIN OUTCOME MEASURES: Post-surgery vomiting episodes, use of rescue therapy, and nausea severity (verbal rating scale). RESULTS: In the 24 hours after surgery, aprepitant 40 mg was more effective than ondansetron for all five endpoints evaluated: (1) no significant nausea (56.4% vs. 48.1%); (2) no nausea (39.6% vs. 33.1%); (3) no vomiting (86.7% vs. 72.4%); (4) no nausea and no vomiting (38.3% vs. 31.4%); and (5) no nausea, no vomiting, and no use of rescue (37.9% vs. 31.2%) (p < 0.035 for the odds ratio for each comparison). Numerically more patients receiving aprepitant 125 mg also achieved these endpoints compared with ondansetron. CONCLUSIONS: These post hoc analyses confirm the favorable efficacy profile of aprepitant for the prevention of post operative nausea and vomiting. PMID- 17845743 TI - Reviewing CATIE for clinicians: balancing benefit and risk using evidence-based medicine tools. AB - BACKGROUND: In order to learn from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study and apply its results to day-to-day clinical practice, it would be useful to quantify the benefits and risks of the studied antipsychotics. SCOPE: Reviewing the CATIE results from the perspective of evidence-based medicine metrics of attributable risk (AR), number needed to treat (NNT), number needed to harm (NNH), and likelihood of being helped or harmed (LHH) helps clinicians translate the CATIE findings for individualized treatment in clinical practice. FINDINGS: Use of these evidence based tools demonstrates that the NNT to avoid a psychiatric hospitalization due to the exacerbation of schizophrenia ranged from 3 to 7 in favor of olanzapine compared with the other antipsychotics. The NNH to produce one treatment-emergent adverse event of weight gain > 7% ranged from -5 to -8 (favoring comparators over olanzapine). Further, when assessing LHH - the likelihood of being helped (avoid a psychiatric hospital admission) compared to the likelihood of being harmed (experience weight gain > 7%) - treatment with olanzapine was consistently associated with greater expectation of benefit than harm (LHH > 1). CONCLUSION: The use of NNT, NNH, and LHH can be helpful in balancing risk versus benefit in selecting antipsychotic treatment. LIMITATIONS: NNT and NNH may vary with baseline risk, and cannot be calculated from continuous variables. LHH may be influenced by an individual's perception of the value of the outcomes compared. PMID- 17845751 TI - [Precise pathological and molecular diagnosis is the premise of relevant anti cancer targeted therapy]. PMID- 17845745 TI - Fetal health surveillance: antepartum and intrapartum consensus guideline. AB - OBJECTIVE: This guideline provides new recommendations pertaining to the application and documentation of fetal surveillance in the antepartum and intrapartum period that will decrease the incidence of birth asphyxia while maintaining the lowest possible rate of obstetrical intervention. Pregnancies with and without risk factors for adverse perinatal outcomes are considered. This guideline presents an alternative classification system for antenatal fetal non stress testing and intrapartum electronic fetal surveillance to what has been used previously. This guideline is intended for use by all health professionals who provide antepartum and intrapartum care in Canada. OPTIONS: Consideration has been given to all methods of fetal surveillance currently available in Canada. OUTCOMES: Short- and long-term outcomes that may indicate the presence of birth asphyxia were considered. The associated rates of operative and other labour interventions were also considered. EVIDENCE: A comprehensive review of randomized controlled trials published between January 1996 and March 2007 was undertaken, and MEDLINE and the Cochrane Database were used to search the literature for all new studies on fetal surveillance both antepartum and intrapartum. The level of evidence has been determined using the criteria and classifications of the Canadian Task Force on Preventive Health Care. SPONSOR: This consensus guideline was jointly developed by the Society of Obstetricians and Gynaecologists of Canada and the British Columbia Perinatal Health Program (formerly the British Columbia Reproductive Care Program or BCRCP) and was partly supported by an unrestricted educational grant from the British Columbia Perinatal Health Program. PMID- 17845752 TI - [The requirements to clinicopathology about targeted therapy for breast cancer]. PMID- 17845753 TI - [Chemotherapy and target-therapy of gastrointestinal tumors call for development of pathology]. PMID- 17845754 TI - [KIT mutation analysis in pathological diagnosis and target-therapy of gastrointestinal stromal tumors: an update]. PMID- 17845756 TI - [Protein overexpression and gene copy number of EGFR and HER2 in colorectal carcinoma]. AB - OBJECTIVE: To investigate the protein expression and gene copy number of EGFR and HER2, and the correlation between the two markers in colorectal carcinomas in Chinese. METHOD: Total 42 samples of paraffin-embedded colorectal carcinomas in tissue microarray format were studied by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for EGFR and HER2 protein expression and gene copy number status, respectively. RESULTS: Among 42 cases evaluated, EGFR scores were 0 in 18 cases, 1+ in 10 cases, 2+ in 5 cases and 3+ in 9 cases. HER2 expression was negative in 39 tumors, 1+ in 1 tumor, 2+ in 1 tumor and 3+ in 1 tumor. For FISH assessing EGFR, 18 (42.9%) cases showed no apparent copy number changes, including 14 (33.3%) cases of disomy and 4 (9.5%) cases of low trisomy, 24 (57.1%) cases showed increased gene copy numbers including high trisomy in 3/42 (7.1%), low polysomy in 9/42 (21.4%) and high polysomy in 12/42 (28.6%) cases. Gene amplification of EGFR is not detected. Four of 42 patients (9.5%) had increased HER2 gene copy number, including 3 patients with high polysomy and 1 patient with gene amplification. Significant association was not seen between EGFR protein expression and the gene copy number, nor between two markers and tumor differentiation. There was a highly significant concordance between the gene amplification and IHC 3+ for HER2 similar to that of breast cancer. CONCLUSIONS: Protein expression and/or increased gene copy number of EGFR is common in colorectal carcinomas but unrelated to pathological features in this cohort. HER2 protein overexpression and/or gene amplification are rare. PMID- 17845757 TI - [Status and clinicopathologic implication of epidermal growth factor receptor mutation in non-small cell carcinoma of lung]. AB - OBJECTIVE: To investigate mutations of epidermal growth factor receptor (EGFR) exon 19 and 21 in non-small cell lung carcinoma and to explore their clinicopathological correlations. METHOD: DNA was extracted from the excised tumor specimens of 66 non-small cell lung carcinoma patients by traditional phenol-chloroform and ethanol precipitation. Exons 19 and 21 were amplified by polymerase chain reaction (PCR), followed by direct sequencing in both sense and antisense directions. RESULTS: EGFR somatic mutations were present in 11 of 66 patients (16.7%), including 7 cases of in-frame deletion involving exon 19 and 4 cases of amino acid substitution involving exon 21. Mutations were more frequently observed in women (9/34, 26.5%) than in men (2/32, 6.3%), in adenocarcinomas (10/43, 23.3%) than squamous (0/13) and adenosquamous carcinomas (1/10). There was no difference in the mutation rates between smokers and non smokers. Those with adenocarcinoma with bronchiolo-alveolar carcinoma (BAC) components had higher frequency of EGFR mutation (6/11) than those without non BAC element (4/32, 12.5%). CONCLUSIONS: The mutations appear to occur in highly selected subgroups of lung cancer patients: adenocarcinomas with BAC components and patients of the female gender. The results may offer practical approach to the rapid identification of lung cancer patients who likely respond to EGFR inhibitor therapy. PMID- 17845758 TI - [Analysis of HER2 gene amplification and its protein expression in 165 cases of breast carcinoma: comparison of chromogenic in-situ hybridization and immunohistochemistry]. AB - OBJECTIVE: To evaluate the sensitivity and specificity of chromogenic in-situ hybridization (CISH) in detecting HER2 gene amplification in breast carcinomas. METHODS: HER2 oncogene amplification and its protein expression in 165 cases of breast carcinoma were investigated by immunohistochemistry (IHC) and CISH. RESULTS: (1) CISH did not detect HER2 gene amplification in 107 cases of IHC negative tumors and 24 cases of IHC 1+ tumors. (2) CISH identified high copy numbers of HER2 gene amplification in 21/22 (95.5%) cases with IHC 3+. (3) In 12 HIC 2+ cases, CISH identified 3 cases of high copy number amplification, 6 cases of low copy number amplification and 3 cases without amplification. CONCLUSIONS: HER2 gene amplification detection by CISH is highly sensitive and has a high concordance with IHC detection of the protein expression. It is concluded that CISH is a tool to evaluate HER2 gene status in breast cancer and can be an implement in conventional pathology laboratories. PMID- 17845759 TI - [Primary diffuse large B-cell lymphoma of testis: a clinicopathologic study of 14 cases]. AB - OBJECTIVE: To study the clinicopathologic features, immunohistochemical findings and prognosis of primary diffuse large B-cell lymphoma (DLBCL) of testis. METHODS: Fourteen cases of primary DLBCL of testis, diagnosed according to the 2001 World Health Organization staging standards for hematopoietic and lymphoid tumors, were retrospectively studied. Immunohistochemical study was performed and follow-up information analyzed. RESULTS: The median age of the patients was 62 years. There were 10 patients in stage I, 3 in stage II and 1 in stage IV. Follow up information was available in 11 patients (78.6%). Three of which were still alive and eight died (with duration of survival ranging from 5 to 19 months). The patients usually presented with unilateral painless enlargement of testis. Histologically, the lymphoma cells of all cases showed a centroblastic appearance. One case belonged to the germinal center B cell-like subtype on immunohistochemical study, while the remaining 13 cases were classified as non germinal center B cell-like subtype. Ten of the 14 cases (71.4%) showed overexpression of p53 protein. Most cases demonstrated high proliferation index. Six of the 14 cases (42.9%) were positive for bcl-2 protein. The overall 1-year, 2-year and 5-year survival rates were 45.5%, 17.0% and 17.0%, respectively. CONCLUSIONS: Most cases with primary DLBCL of testis were of peripheral activated B-cell origin. The prognosis is usually not favorable, with propensity of local relapse and systemic dissemination. Accurate pathologic diagnosis relies on detailed histologic examination and immunohistochemical study. PMID- 17845760 TI - [Expression of neutral endopeptidase and motility-related protein-1 in cutaneous malignant melanoma]. AB - OBJECTIVE: To study the expression of neutral endopeptidase (CD10) and motility related protein-1 (CD9) in malignant melanoma and their clinical significance. METHODS: Immunohistochemical study for CD10 and CD9 using Streptavidin-biotin complex technique was carried out in 48 cases of primary cutaneous malignant melanoma (CMM), 23 cases of metastatic melanoma and 23 cases of benign nevus. RESULTS: The positivity rate of CD10 was highest in metastatic melanoma and lowest in benign nevus (P < 0.01). In contrast, the positivity rate of CD9 in metastatic melanoma was lower than that in CMM (P < 0.05). The expression of CD9 was inversely correlated with that of CD10 in malignant melanoma (CMM: r = -0.40, P = 0.005; metastatic MM: r = -0.44, P = 0.034). The expression of CD10 and CD9 in CMM also correlated with tumor histology, Clark's level of invasion and presence of nodal metastasis. A similar relationship was also observed for CD10 and CD9 expression in stromal fibroblasts of CMM (r = -0.43, P = 0.007). CONCLUSIONS: CD10 and CD9 expression correlates with the invasiveness and metastatic potential of malignant melanoma; both factors may demonstrate a counteracting effect. These two markers have potential implications in prognostic assessment of CMM. Stromal fibroblasts may also play an important role in the progression of CMM. PMID- 17845761 TI - [Nodal versus extranodal diffuse large B-cell lymphoma: comparison of clinicopathologic features, immunophenotype and prognosis]. AB - OBJECTIVE: To study the clinicopathologic features and outcome of patients with diffuse large B-cell lymphoma (DLBCL), and to compare the differences between DLBCL of nodal and extranodal origins. METHODS: One hundred and forty-two cases of de novo DLBCL collected during a 10-year period were reviewed. The clinicopathologic features and follow-up (2 - 108 months) data were analyzed. Tissue microarray blocks were performed and immunohistochemical studies using antibodies against CD10, bcl-6 and MUM1 were carried out. The cases were then further categorized into germinal center B cell-like (GCB) and non-GCB subtypes. RESULTS: Primary gastrointestinal DLBCL often presented as early-stage disease (stage I or II) and was associated with low international prognostic index. They showed better prognosis than DLBCL of nodal and other extranodal origins. The positivity rates of CD10, bcl-6 and MUM1 were 19%, 51% and 58%, respectively. 36% of the cases belonged to GCB, while the remaining 64% were non-GCB. In general, DLBCL of extranodal origin showed more frequent bcl-6 expression than nodal DLBCL. As for extranodal DLBCL, GCB immunophenotype was often seen in thyroid and breast tumors, while testicular DLBCL usually carried a non-GCB immunophenotype. CONCLUSIONS: DLBCL of various origins show a diversified GCB and non-GCB differentiation. Nodal and extranodal DLBCL, as well as extranodal DLBCL from different primary sites, carry different biologic characteristics and prognostic implications. PMID- 17845762 TI - [Histologic classification and prognostic implication of pseudomyxoma peritonei]. AB - OBJECTIVE: To clarify the various diagnostic connotations of pseudomyxoma peritonei (PMP) and to study their prognostic implications. METHODS: Clinicopathologic features and follow-up data of 40 patients with PMP diagnosed in The General Hospital of PLA were retrospectively reviewed. The cases were histologically classified into 3 subcategories: disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and PMCA with intermediate or discordant features (PMCA-I/D). The survival rate was calculated using Kaplan-Meier method and the difference was statistically analyzed. RESULTS: Twelve of the 40 patients died on follow up. The duration of survival ranged from 2 to 348 months (medium = 37.5 months). In general, the 3-year, 5-year and 10 year survival rates were 79.0%, 69.4% and 53.0%, respectively. The mean age of the patients at the time of diagnosis was 50.3 years (age range = 22 to 76 years). The male-to-female ratio was 1:1. The age and sex of patients, frequency of operation and presence of ovarian involvement did not correlate with duration of survival. On the other hand, the presence of appendiceal tumor, parenchymal invasion of abdominal viscera, cellularity, architecture, nuclear atypia and mitotic activity of the peritoneal lesion significantly correlated with survival. There was also significant difference in survival between DPAM, PMCA-I/D and PMCA subcategories (P = 0.018). The difference in survival rate between PMCA-I/D and PMCA subgroups however was not statistically significant (P = 0.096). The outcome of DPAM was significantly better when compared with the combined group of PMCA I/D and PMCA (P = 0.006). CONCLUSIONS: In general, the 10-year survival rate of PMP was low, despite the relatively benign-looking or low-grade pathologic appearance. Peritoneal lesions with higher cellularity, conspicuous nuclear atypia and higher mitotic activity are associated with a lower survival rate. The prognosis was even worse in the presence of appendiceal carcinoma or parenchymal invasion of abdominal viscera. It is thus advisable to subclassify PMP into DPAM, PMCA and PMCA-I/D, due to the difference in prognostic implication. PMID- 17845763 TI - [Roles of immunohistochemistry and detection of SYT-SSX fusion gene in diagnosis of synovial sarcoma]. AB - OBJECTIVE: To assess the diagnostic values of immunohistochemistry and SYT-SSX fusion gene detection for synovial sarcoma. METHODS: Based on clinical features, histological and immunohistochemical profiles, 195 cases of tumors were divided into three diagnostic categories: definitive synovial sarcoma, probable synovial sarcoma and possible synovial sarcoma. RT-PCR Detection of the SYT-SSX fusion gene was performed using paraffin embedded tissue samples. Comparison between RT PCR and immunohistochemistry results was carried out and their diagnostic value was evaluated. RESULTS: There were 62 (31.8%) definite synovial sarcomas, 49 (25.1%) probable synovial sarcomas and 84 cases (43.1%) possible synovial sarcomas. SYT-SSX fusion gene was detected in 140 (78.2%) cases overall, including 94.7% (54/57) definite synovial sarcomas, 86.0% (37/43) probable synovial sarcomas and 62.0% (49/79) possible synovial sarcomas. In tumors in the certain and probable synovial sarcoma categories, the positive rates of epithelial membrane antigen (EMA) were significantly higher in the SYT-SSX positive cases than SYT-SSX-negative cases (P = 0.022, P = 0.010, respectively). EMA was positively correlated with the presence of SYT-SSX (r(s) = 0.431, P = 0.001, r(s) = 0.463, P = 0.002, respectively). However, such a correlation was not seen in cytokeratin (CK), vimentin or S-100 protein immunostains (P > 0.05). In tumors of possible synovial sarcoma category, there were no significant differences of CK, EMA, vimentin or S-100 protein between SYT-SSX-positive and SYT-SSX-negative tumors. CONCLUSIONS: SYT-SSX fusion gene detection is not needed when the conventional approaches are diagnostic. EMA positivity has a similar diagnostic value to that of SYT-SSX by RT-PCR for tumors in the probable synovial sarcoma category. However, detection of SYT-SSX is very important for diagnosis of the tumors in the category of possible synovial sarcoma. PMID- 17845764 TI - [Retrospective analysis of 15,393 cases of liquid-based cervical cytology, with histologic correlation]. AB - OBJECTIVE: To study the rate of concordance between positive cervical cytologic interpretation based on liquid-based preparations and subsequent histologic diagnosis. METHODS: Liquid-based cervical cytology (SurePath) was carried out in 15,393 patients. Cases with the cytologic diagnosis of epithelial cell abnormality were further investigated by human papillomavirus (HPV) DNA testing (Hybrid Capture II) for the high-risk HPV DNA, colposcopic examination and multiple cervical biopsies. The 2001 version of The Bethesda System for reporting gynecologic cytology was applied. Positive cytologic diagnosis included atypical squamous cells of undetermined significance (ASC-US) or above. Histologic correlation was available in some of the patients. The rate of concordance between positive cytologic interpretation and subsequent histologic diagnosis was calculated. RESULTS: Amongst the 15,393 liquid-based cytology cases studied, the cytologic diagnosis of 7 cases squamous cell carcinoma were all concordance with histologic diagnosis, while the rates for high-grade and low-grade squamous intraepithelial lesions were 93.6% (103/110) and 82.0% (443/540), respectively. A positive correlation was also demonstrated between detection of high-risk HPV DNA, positive cytologic interpretation and positive histologic diagnosis. CONCLUSION: Liquid-based cytologic preparation, when coupled with standardized reporting using the Bethesda System 2001, can achieve a high diagnostic accuracy of cervical epithelial abnormalities. PMID- 17845765 TI - [The roles of microRNAs in hematopoiesis and hematopoietic malignancies]. PMID- 17845766 TI - [Application of immunocytochemistry in exfoliative cytology samples]. PMID- 17845767 TI - [Detection of t (11; 18) and rearrangement of bcl-10 in paraffin-embedded samples using interphase fluorescence in-situ hybridization]. PMID- 17845769 TI - [Clear cell chondrosarcoma: report of a case]. PMID- 17845770 TI - [Intraspinal mature teratoma cervical spine: report of a case]. PMID- 17845771 TI - [Sclerosing mesenteritis: report of a case]. PMID- 17845772 TI - [Improvement of the treatment level of complex congenital heart diseases]. PMID- 17845773 TI - [Several aspects of the hybrid approaches to congenital heart diseases]. PMID- 17845774 TI - [Analysis surgical results of 113 patients with complete transposition of the great arteries]. AB - OBJECTIVE: To review and analysis the surgical results of 113 arteries Switch operations. METHODS: One hundred and thirteen patients had been repaired by arterial Switch operation from January 2001 to December 2005. There were 60 patients with transposition of the great arteries and intact ventricular septum (TGA/IVS), 53 patients with transposition of great arteries and ventricular septal defect (TGA/VSD). The lowest body weight was 2.3 kg, and the youngest operative age was 6 h. The arteries Switch operation was performed underwent deep hypothermic circulation arrest and low-flow perfusion. RESULTS: The total mortality was 9.7%. There were 5 deaths among TGA/IVS (8.3%), 6 deaths among TGA/VSD (11.3%). Following improvement of surgical technique, post-operative management and cardiopulmonary bypass, the operative mortality was decreased from 16.6% to 5.5%. CONCLUSIONS: The main reason for operative mortality was abnormal coronary arteries. The incidence of abnormal coronary arteries was high at TGA/VSD. The surgical results was not infected by the position of great arteries. The low cardiac output was appeared if the ratio of left ventricular pressure and right ventricular pressure less than 0.6. PMID- 17845775 TI - [Surgical treatment of complex congenital heart diseases with extracardiac conduit total cavopulmonary connection]. AB - OBJECTIVE: To report the experience of extracardiac conduit total cavopulmonary connection (ECTCPC) in surgical treatment of complex congenital heart diseases. METHODS: From 1998 to 2006, 68 patients underwent ECTCPC for complex congenital heart diseases. Among them, 45 had functional univentricle with transposition of the great artery (TGA) and pulmonary artery valve stenosis, 19 had tricuspid atresia with hypoplasia of right ventricle, 4 had Ebstein's anomaly with hypoplasia of right ventricle. Six had left superior vena cava, 18 had received Bidirectional Glenn operation; Fifty-seven cases were performed under cardiopulmonary bypass with general anesthesia and hypothermia, 11 cases were performed without cardiopulmonary bypass. RESULTS: There were two death, the mortality was 2.9%. All patients were followed up from 1 to 8 years with no clinical symptoms and have been doing well. The arterial oxygen saturation was 90% - 96%, the cardiac function were in NYHA class I - II. CONCLUSION: The extra cardiac conduit TCPC is a simple procedure and superior to other type of Fontan procedure in most patients. PMID- 17845776 TI - [Study of cardiopulmonary adaptation during exercise in patients after extracardiac conduit total cavopulmonary connection]. AB - OBJECTIVE: To study cardiopulmonary physiology during exercise in patients after extracardiac total cavopulmonary connection (ECTCPC). METHODS: Twenty-six patients were studied after ECTCPC by exercise testing with bicycle treadmill protocol. Heart rate (HR), blood pressure (BP), respiratory frequency (RF) and pulse oxygen saturation (SpO(2)) were measured continuously; twenty-six patients suffered from Fallot 4 underwent biventricular repair were also studied as control group. RESULTS: In ECTCPC group, HR, BP, SpO(2) and RF all increased with exercise below 3 grade; when exceed 4 grade, BP, SpO(2) decreased and RF kept increasing. Compared with control group, HR, RF were higher (t = 2.13, P < 0.05; t = 2.31, P < 0.05), SpO(2) was lower (t = 2.46, P < 0.05) under the quiescent condition; When exceed 3 grade, HR, BP, SpO(2) decreased more significantly, but RF increased continuously. In fenestration group after ECTCPC, HR reached the top at 5 grades, but in group without fenestration it reached the top at 3 grades; In the whole process of exercising, RF kept higher and SpO(2) kept lower in fenestration group. CONCLUSIONS: The ECTCPC patients showed obviously exercise limitation. Totally bypass of sinoatrial node in this operation may have some adverse effects on the integer regulation of HR. PMID- 17845777 TI - [The application of bidirectional Glenn procedure on 68 pediatric cases with functional univentricle heart]. AB - OBJECTIVE: To analyze 68 pediatric cases with functional univentricle heart who underwent bidirectional Glenn procedure during from April 1998 to December 2005. METHODS: There were 47 males and 21 females in this group, aged from 5 months to 14 years old and weighed from 6.7 to 30.0 kg. Among them, 39 cases were received bidirectional Glenn procedure on the right side, 13 cases on the left side and 16 cases on both sides. Three cases had the pulmonary artery banded; one case had the pulmonary artery ligated;one case had the original A-P shunt cut off; six cases had the PDA ligated; four cases had the MAPCAs cut off; one case had TAPVC corrected contemporarily; two cases of PAPVC were also corrected; four cases had the atrial-ventricular valve repaired. RESULTS: Three cases died. The mortality was 4.4%. The mean post-operative pressure of super vena cava was (15.9 +/- 2.4) mm Hg (1 mm Hg = 0.133 kPa), higher than the pre-operative one (8.3 +/- 1.8) mm Hg (P < 0.01). The mean post operative SpO(2) was (89.3 +/- 4.2)%, higher than the pre-operative one (78.4 +/- 6.0)% (P < 0.01). CONCLUSIONS: Bidirectional Glenn procedure is of satisfied effect on surgical treatment for functional univentricle heart. The persistent forward flow from pulmonary artery should be reserved in bidirectional Glenn procedure. PMID- 17845780 TI - [Immunosuppressive therapy after human lung transplantation]. AB - OBJECTIVE: To summarize the diagnosis and treatment of acute rejection after lung transplantation and to discuss optimized immunosuppressive therapy. METHODS: Between November 2002 and June 2006, 16 patients underwent operations on lung transplantation, 7 cases on single-lung transplantation and 9 cases on bilateral lung transplantation. Immunosuppressive therapy was new triple drug maintenance regimen including tacrolimus (Tac), mycophenolate mofetil (MMF) and steroids, and (or) daclizumab. RESULTS: Eight cases in new triple drug maintenance regimen with daclizumab. There is no acute rejection in 6 months. Except 2 of the 8 cases died of early post-lung transplantation sever pulmonary edema and dysfunction, 3 of the rest 6 cases underwent acute rejection incident about 21.4% (3/14). CONCLUSION: In this group the new triple drug maintenance regimen including tacrolimus (Tac), mycophenolate mofetil (MMF) and steroids, and (or) daclizumab acquired beneficial effect in preventing acute rejection after lung transplantation. PMID- 17845782 TI - [Clinical therapeutic effect of esophageal carcinoma with hand video assisted surgery]. AB - OBJECTIVE: To explore the clinical therapeutic effect of esophageal carcinoma with hand video assisted surgery. METHODS: Forty cases which C TNM stage was T3N1M0 received hand video assisted surgery (HVATS group), 40 cases received routine operation (control group). Recurrence survival analysis of each group was analyzed with SPSS10.0 software according to the date of the stage and survival rate. RESULTS: All group have satisfied surgical result. All patients have good quality of life. The 3 year survival rate was 52.7% in HVATS group and 51.3% in control group. The difference of survival rate was no significance. CONCLUSION: Hand video assisted surgery for esophageal carcinoma had same result as routine thoracic operation. Short operation time, less trauma and fast recovery are the advantages of hand video assisted surgery. PMID- 17845783 TI - [Analysis of complications of osteosarcoma around knee treated by resection and replacement of tumor-type prosthesis]. AB - OBJECTIVE: To summarize the effects and complications of osteosarcoma around knee treated by wide resection and replacement by the tumor-type prosthesis. METHODS: Between July 1997 and July 2004, 117 patients with osteosarcoma around the knee had been treated with wide resection and reconstruction with prosthesis. Alcohol devitalized tumor bone prosthetic composite were used for reconstruction in 13 patients, and allograft prosthetic composite (APC) were used in 25 patients. All patients accepted 2 cycles of chemotherapy before the surgery. RESULTS: The mean follow-up period was 3.5 years (1 - 8 years). Nine patients had failure of union at the graft-host junction. Fracture of the stem of the prosthesis occurred in 5 patients, late infection was found in 19 patients, and aseptic loosening occurred in 3 patients. Bone fracture occurred in 1 patient and prosthesis sinking occurred in 2 patients. CONCLUSIONS: The tumor-type prosthetic reconstruction offers the best knee function after resection of the tumor around the knee, and recurrence rate can be accepted. However, the tumor-type prosthesis needs further improvement because of the high complication rate. PMID- 17845784 TI - [Comparative study on precision of vertebral screw insertion for idiopathic thoracic scoliosis between by thoracoscopy and by mini anterior thoracotomy]. AB - OBJECTIVE: To compare the precision of the vertebral screw insertion in treating idiopathic thoracic scoliosis by thoracoscopy with that by mini anterior thoracotomy. METHODS: Ten patients with an average Cobb angle of 52.9 degrees were operated thoracoscopically (group A), and twenty-one patients with an average Cobb angle of 45.4 degrees were operated by mini anterior thoracotomy (group B). In order to determine the accuracy of screw placement, several parameters were measured postoperatively on each instrumented level of CT scan, including the entry point and entry direction of screw, the relationships between the screw tip and aorta as well as spinal canal. The safety of screw placement was determined at the position of screw to the vertebral canal and the aorta, and the results of CT analysis were designated as; D, the screw tip was distant from the aorta (> or = 1 mm); A, the screw tip was adjacent to the aorta (< 1 mm); C, the screw tip was felt to be against the aorta and creating contour deformity. The screw which had a bi-cortical purchase but was distant from the aorta and vertebral canal was defined as a satisfied screw. RESULTS: 73 screws were inserted into patients of Group A, and 162 into patients in Group B. Parameters measured on CT image and X-ray showed no difference between these two groups (P > 0.05). There is no difference (P > 0.05) between A and B group of percentages in D (89.0% vs. 80.2%), in bi-cortical purchase (89.0% vs. 87.0%), and in satisfaction of screw placement (74.0% vs. 66.0%). CONCLUSION: Thoracoscopic and mini-open thoracotomic anterior correction are safe and effective to correct idiopathic right thoracic scoliosis with satisfied correction. Vertebral screws placed by both techniques have the same satisfied accuracy, safety, bi-cortical purchase and the satisfaction rate either in total screws or in the corresponding area. PMID- 17845785 TI - [The use of balloon catheter in surgical treatment of renal neoplasm with inferior vena cava thrombus]. AB - OBJECTIVE: To improve the treatment of renal neoplasm with tumor thrombus in the inferior vena cava. METHODS: From May 2005 to May 2006, 9 cases of renal neoplasm with tumor thrombus were treated with balloon catheters to block inferior vena cava under the level of liver vena during the operations. Among the patients, 6 were male and 3 were female. The patients were from 20 to 76 years old (average 53). RESULTS: All cases were succeed by transabdominal incisions. The average length of tumor thrombus was 5.0 cm (3.0 - 6.7 cm). The blood pressure and heart rate were stable during operations. No intraoperative or postoperative complications occurred. The follow up ranged from 6 to 18 months. One patient died at 6 months after surgery. The others lived well. CONCLUSION: The use of balloon catheter during surgical treatment of renal neoplasm with inferior vena cava thrombus is suitable for type II and III tumor thrombus. PMID- 17845787 TI - [The use of balloon catheter in surgical treatment of renal angiomyolipoma with a caval thrombus: 1 case report and literature review]. AB - OBJECTIVE: To present one cases of the use of balloon catheter in surgical treatment of renal angiomyolipoma involving the renal vein and vena cava as a tumor thrombus and review literatures. METHODS: Abdominal ultrasound and CT and MRI demonstrated a large right renal mass with tumor thrombus in the inferior vena cava. Right nephrectomy and en-bloc removal of the intra caval tumor thrombus were performed. A balloon catheter was used to block vena cava under the level of liver vena during the operation. RESULTS: The pathological diagnosis was angiomyolipoma. The length of the tumor thrombus was 6.5 cm. The patient recovered well 1 year after surgery. CONCLUSION: Renal angiomyolipoma with a tumor thrombus should be paid more attention. PMID- 17845788 TI - [Effect of increased posterior tibial slope or partial posterior cruciate ligament release on knee kinematics of total knee arthroplasty]. AB - OBJECTIVE: To compare the effects of increased posterior tibial slope or partial posterior cruciate ligament (PCL) release on knee kinematics of total knee arthroplasty (TKA). METHODS: Anteroposterior laxity, rotational laxity, varus and valgus laxity and maximum flexion angle were evaluated in 6 normal cadaver knees and the knees after TKA at flexion 0 degrees , 30 degrees , 60 degrees , 90 degrees and 120 degrees . Then the femoral prosthesis was shifted 5 mm posteriorly to simulate the tightly implanted knee. The same tests were performed on the tightly implanted knees. After that, the posterior tibial slope was increased 4 degrees or the PCL was partially released, and the same tests were made as in the normal knees respectively. Statistical analysis of the results was made using student's t test. RESULTS: Anteroposterior laxity, rotational laxity and varus and valgus laxity of the tightly implanted knees at flexion 30 degrees , 60 degrees , 90 degrees and 120 degrees were significantly less than those of the normal TKA knees (P < 0.05). Compared with the tightly implanted knees, anteroposterior laxity, rotational laxity and varus and valgus laxity at flexion 30 degrees , 60 degrees , 90 degrees and 120 degrees significantly improved after increased 4 degrees posterior tibial slope (P < 0.05); in the partial PCL released group, anteroposterior laxity at flexion 30 degrees , 60 degrees , 90 degrees and 120 degrees was significantly improved (P < 0.05), varus and valgus laxity was significantly improved only at flexion 90 degrees (P < 0.05), and rotational laxity was significantly improved at flexion 30 degrees , 60 degrees and 90 degrees (P < 0.05). Compared with PCL released group, varus and valgus laxity at flexion 30 degrees , 60 degrees and 90 degrees and rotational laxity at flexion 0 degrees , 30 degrees , 60 degrees and 90 degrees were significantly improved in the group of increased 4 degrees posterior tibial slope (P < 0.05). Maximum flexion angle of the tightly implanted knee (120.4 degrees ) was less than that of the normal TKA knees (130.3 degrees , P < 0.05) and that of increased 4 degrees posterior tibial slope group (131.1 degrees , P < 0.05). There was no significant difference at the maximum flexion angle between the increased 4 degrees posterior tibial slope group and the PCL released group (131.1 degrees vs 124.0 degrees , P = 0.0816). CONCLUSIONS: Anteroposterior laxity, varus and valgus laxity, rotational laxity and maximum flexion angle of the tightly implanted knees are less than those of the normal TKA knees. After increased 4 degrees posterior tibial slope, these indexes are improved significantly. Partial PCL released can significantly improve the anteroposterior laxity and had less effect on the varus and valgus laxity, rotational laxity and maximum flexion angle. So, a knee that is tight in flexion can be more likely to be corrected by increasing posterior tibial slope than by partially releasing PCL. PMID- 17845789 TI - [Research about schwann cells and PLGA implanted to rat transected spinal cord]. AB - OBJECTIVE: To investigate the recovery of rat transected spinal cord injury after implantation of Schwann cells combined with poly (lactide-co-glycolide) (PLGA). METHODS: Schwann cells were expanded, co-cultured with PLGA for 9 days in vitro, and then analyzed with scanning electron microscope (SEM). Rat spinal cord at the level of T(9) was transected. Schwann cells labeled with BrdU and PLGA scaffold were implanted to injury site. After 1, 3, 6 months, BrdU/MBP immunohistochemistry double staining, semi-thin sections stained thionin and ultra-thin section were performed to investigate myelin renew. BBB open field locomotion, motor evoked potential (MEP), compound muscle action potential (CMAP) and somatosensory evoked potential (SEP) were recorded. RESULTS: Schwann cells grew well on PLGA under SEM. BrdU/MBP double positive cells would been seen, remyelination was thin and formed by Schwann cells at 6 months later under electron microscope (EM). BBB behavioral tests revealed no significant difference in recovery comparing with experiment group and control group. The results of MEP, CMAP and SEP showed no significant improvement in the conduction of spinal cord. CONCLUSIONS: There are the compatibility between Schwann cells and PLGA. Although remyelination was found in morphology, function conduction of spinal cord failed to be established. PMID- 17845799 TI - The KCNE1 beta-subunit exerts a transient effect on the KCNQ1 K+ channel. AB - The KCNE1 beta-subunit is a modulatory one-trans-membrane segment accessory protein that alters KCNQ1 K(+) channel current characteristics, though it is not required for channel expression. The KCNE1 and KCNQ1 interaction was investigated by looking for effects of expression time on channel currents in Xenopus laevis oocytes. We found that long-time expression of KCNQ1+KCNE1 (2-14 days) resulted in gradual changes in current characteristics resembling a disappearance of KCNE1 from the oocyte plasma membrane. Towards the end of the expression period the current of oocytes expressing KCNQ1+KCNE1 was indistinguishable from those expressing KCNQ1 alone. No time dependent effect was seen in oocytes expressing KCNQ1 alone or a concatamer of KCNQ1 and KCNE1. Brefeldin A was tested, showing that measured current was independent of exocytosis (decreased capacitance) thus eliminating a continuous displacement-explanation. Based on the functional data, we suggest that the interaction between KNCE1 and KCNQ1 may be reversible and transient in a "Kiss & Go" manner, supporting a physiological role for KCNE1 as a dynamic regulatory molecule. PMID- 17845800 TI - Sonic hedgehog expression during early tooth development in Suncus murinus. AB - Tooth development is a highly organized process characterized by reciprocal interactions between epithelium and mesenchyme. However, the expression patterns and functions of molecules involved in mouse tooth development are unclear from the viewpoint of explaining human dental malformations and anomalies. Here, we show the expression of sonic hedgehog (Shh), a potent initiator of morphogenesis, during the early stages of tooth development in Suncus murinus. Initially, symmetrical, elongated expression of suncus Shh (sShh) was observed in the thin layer of dental epithelial cells along the mesial-distal axis of both jaws. As the dental epithelium continued to develop, sShh was strictly restricted to the predicted leading parts of the growing, invaginating epithelium corresponding to tooth primordia and enamel knots. We propose that some aspects of Shh function in tooth development are widely conserved in mammalian phylogeny. PMID- 17845801 TI - Restoring E-cadherin-mediated cell-cell adhesion increases PTEN protein level and stability in human breast carcinoma cells. AB - The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a well characterized tumor suppressor that negatively regulates cell growth and survival. Despite the critical role of PTEN in cell signaling, the mechanisms of its regulation are still under investigation. We reported here that PTEN expression could be controlled by overexpression or knock-down of E-cadherin in several mammary carcinoma cell lines. Furthermore, we showed that the accumulation of PTEN protein in E-cadherin overexpressing cells was due to increased PTEN protein stability rather than the regulation of its transcription. The proteasome-dependent PTEN degradation pathway was impaired after restoring E cadherin expression. Moreover, maintenance of E-cadherin mediated cell-cell adhesion was necessary for its regulating PTEN. Altogether, our results suggested that E-cadherin mediated cell-cell adhesion was essential for preventing the proteasome degradation of PTEN, which might explain how breast carcinoma cells which lost cell-cell contact proliferate rapidly and are prone to metastasis. PMID- 17845802 TI - Co-localization and interaction of DPYSL3 and GAP43 in primary cortical neurons. AB - Dihydropyrimidinase-like 3 (DPYSL3) and GAP43 are both involved in neurite outgrowth, a crucial process for the differentiation of neurons. The present study shows for the first time that DPYSL3 co-localizes with GAP43 in primary cortical neurons. Further co-immunoprecipitation and overlay assay showed the ability of both recombinant and endogenous DPYSL3 to bind GAP43, indicating a specific interaction between DPYSL3 and GAP43 in primary cortical neurons. PMID- 17845803 TI - Expression patterns of calretinin, calbindin and parvalbumin and their colocalization in neurons during development of Macaca monkey retina. AB - The developmental expression of calbindin (CalB), calretinin (CaR) and parvalbumin (PV) was followed in Macaca monkey retina using single and double immunolabeling to identify which proteins provide distinctive labels for specific cell types and to clarify the role of these proteins during development. Ganglion cells (GC) expressed PV at fetal day (Fd)55 and CaR and CalB by Fd85. CaR was downregulated after birth. Separate subsets of amacrine (AM) cells expressed CaR and CalB at Fd65-70. After Fd115, many CaR+ AM coexpressed CalB. After Fd120 a few AM expressed PV and these added CaR and CalB after birth. A subset of horizontal cells (HZ) expressed CaR and CalB at Fd70. Slightly later all HZ express PV and CaR while the early subset is CalB+/PV+/CaR+. CaR downregulates in all HZ after birth. The DB3 cone bipolar cells (BP) under the HZ label for CalB by Fd90-110 while a probable OFF BP cell body just above the AM layer becomes CaR+ near birth with labeling increasing after birth. All cones outside of the fovea label for CalB by Fd125. Foveal cones, rods, most BP and Muller glia do not label for these proteins at any age. The complex patterns of up- and down regulation found in Macaca retina are similar to previous reports of expression in human retina, but in many instances are quite different than earlier reports of CaR, CalB and PV expression patterns in monkey central visual centers. This makes it highly likely that each protein plays a specific but undetermined role(s) in each visual center, and that its expression is controlled at a given stage of retinal development by multiple intrinsic and extrinsic factors. PMID- 17845804 TI - Molecular characterisation of a second structurally unusual AR-Smad without an MH1 domain and a Smad4 orthologue from Echinococcus multilocularis. AB - Members of the transforming growth factor-beta/bone morphogenetic protein (TGF beta/BMP) family of cytokines play crucial roles in animal development and are candidate molecules for host-parasite cross-communication in helminth diseases. TGF-beta/BMP-signalling involves binding of the cytokines to receptor kinases which subsequently activate intracellular transcription factors of the Smad family. We have previously characterized two members of the receptor-regulated Smad (R-Smad) family, EmSmadA and EmSmadB, from the human parasitic cestode Echinococcus multilocularis and now present evidence for two additional Smads that are expressed by the larval stages of the parasite. The full-length cDNAs coding for a third R-Smad, EmSmadC, and a common mediator Smad (Co-Smad), EmSmadD, were characterized. While EmSmadD displayed a typical Co-Smad structure, EmSmadC lacked the N-terminal MH1 domain which is typically found in Smads. In yeast two-hybrid analyses, EmSmadC and EmSmadD were capable of homo- and heterodimer formation with other Echinococcus Smads. Furthermore, EmSmadC displayed autonomous transcription activation activity and interacted with EmSkip, a member of the SNW/SKIP family of transcriptional regulators. In a heterologous expression system, EmSmadC was specifically phosphorylated by mammalian TGF-beta receptors, indicating that it is a member of the AR-Smad sub family. Finally, in activity assays, the parasite's Erk-like kinase EmMPK1 phosphorylated EmSmadD, indicating cross-regulation between mitogen-activated protein kinase cascade- and TGF-beta/BMP-signalling in Echinococcus. The data presented herein significantly broaden our knowledge of Smad-signalling factors in E. multilocularis and will facilitate studies on TGF-beta/BMP-regulated genes in the parasite as well as TGF-beta/BMP mediated host-parasite cross-interaction during alveolar echinococcosis. PMID- 17845805 TI - Increased P-glycoprotein expression and decreased phenobarbital distribution in the brain of pentylenetetrazole-kindled rats. AB - The purposes of this study were to investigate whether P-glycoprotein (P-GP) is overexpressed in the brain of pentylenetetrazole (PTZ)-kindled rats, and to investigate the effects of P-GP up-regulation on the distribution of phenobarbital (PB) in brain and its antiepileptic effects. Kindled rats were developed using a subconvulsive dose of PTZ (30 mg/kg, once every 2 days, i.p.) for 24 days. P-GP expression and function were measured by Western blot analysis and rhodamine 123 (Rho 123) distribution in brain. Kindled rats received 10 mg/kg of PB alone or co-administration of cyclosporine A (CsA, 5 mg/kg). At 60 min after administration of PB, concentrations of PB in brain and plasma were measured and the tissue-to-plasma concentration ratios of PB were calculated. Anticonvulsive effects of PB (13.2 mg/kg) alone or co-administration of CsA on the kindled rats were observed. The results showed that kindling resulted in 1.7 fold increase of P-GP level in brain, accompanied by significant decrease of tissue-to-plasma concentration ratios of Rho 123 and PB in hippocampus and cortex without affecting their concentrations in plasma. Co-administration of CsA reversed the decrease of PB concentration in brain without affecting PB level in plasma and significantly potentiated the anticonvulsive effects of PB. The present study demonstrated that chronic PTZ-kindling might increase P-GP expression and function in brain of rat, resulting in decrease of Rho 123 and PB levels in brain tissues. Co-administration of CsA increased PB levels in brain and enhanced anticonvulsive effects of PB by inhibiting P-GP function. PMID- 17845807 TI - A selective, non-peptide caspase-1 inhibitor, VRT-018858, markedly reduces brain damage induced by transient ischemia in the rat. AB - Numerous preclinical studies have reported neuroprotective effects of new agents in animal studies. None of these agents has yet translated into a successful clinical trial and therefore to a new therapy. There are many possible reasons for this failure, including poor design of clinical trials, mismatch between preclinical and clinical protocols, and insufficient preclinical data. The enzyme caspase-1 has been implicated in neuronal death. Deletion of the caspase-1 gene, or administration of partially selective inhibitors, reduces neuronal injury induced by cerebral ischemia in rodents. We report here, for the first time, that VRT-018858, the non-peptide, active metabolite of the selective caspase-1 inhibitor pro-drug, pralnacasan, markedly reduced ischemic injury in rats. VRT 018858 was neuroprotective when delivered at 1 and 3h (42% and 58% neuroprotection, respectively) but not 6h after injury, and protection was sustained 7 days after the induction of ischemia (66% neuroprotection). These data confirm caspase-1 as an important target for intervention in acute CNS injury, and propose a new class of caspase-1 inhibitors as highly effective neuroprotective agents. PMID- 17845806 TI - Comparing analgesia and mu-opioid receptor internalization produced by intrathecal enkephalin: requirement for peptidase inhibition. AB - Opioid receptors in the spinal cord produce strong analgesia, but the mechanisms controlling their activation by endogenous opioids remain unclear. We have previously shown in spinal cord slices that peptidases preclude mu-opioid receptor (MOR) internalization by opioids. Our present goals were to investigate whether enkephalin-induced analgesia is also precluded by peptidases, and whether it is mediated by MORs or delta-opioid receptors (DORs). Tail-flick analgesia and MOR internalization were measured in rats injected intrathecally with Leu enkephalin and peptidase inhibitors. Without peptidase inhibitors, Leu-enkephalin produced neither analgesia nor MOR internalization at doses up to 100 nmol, whereas with peptidase inhibitors it produced analgesia at 0.3 nmol and MOR internalization at 1 nmol. Leu-enkephalin was 10 times more potent to produce analgesia than to produce MOR internalization, suggesting that DORs were involved. Selective MOR or DOR antagonists completely blocked the analgesia elicited by 0.3 nmol Leu-enkephalin (a dose that produced little MOR internalization), indicating that it involved these two receptors, possibly by an additive or synergistic interaction. The selective MOR agonist endomorphin-2 produced analgesia even in the presence of a DOR antagonist, but at doses substantially higher than Leu-enkephalin. Unlike Leu-enkephalin, endomorphin-2 had the same potencies to induce analgesia and MOR internalization. We concluded that low doses of enkephalins produce analgesia by activating both MORs and DORs. Analgesia can also be produced exclusively by MORs at higher agonist doses. Since peptidases prevent the activation of spinal opioid receptors by enkephalins, the coincident release of opioids and endogenous peptidase inhibitors may be required for analgesia. PMID- 17845808 TI - Genetics and mathematics: evidence from Prader-Willi syndrome. AB - Mathematical abilities were tested in people with Prader-Willi syndrome (PWS), using a series of basic mathematical tasks for which normative data are available. The difference between the deletion and the disomy variants of this condition was explored. While a wide phenotypic variation was found, some basic findings emerge clearly. As expected from previous literature, deletion and disomy participants were found to differ in their degree of impairment, with disomy being overall the most spared condition. However, the tasks selectively spared in the disomy condition are not necessarily the easiest ones and those that discriminate less the PWS group from controls. It rather seems that disomy patients are spared, with respect to deletion, in tasks entailing transcoding and comparison of numbers in the Arabic code. Overall a particular difficulty was detected in reliably performing parity judgments. This task has been shown to be very frequently spared after a brain injury, even in severe aphasic conditions. The most interesting result is the sparing in analog number scale, whereby PWS seem, overall, to outperform controls. This finding may help in understanding previously reported, surprising results about cognitive skills in PWS. Elevated performances in PWS may result from life-long hyper-reliance on one visuo-spatial system in presence of underdevelopment of the other. PMID- 17845809 TI - Clinical relevance of pressure-dependent scattering at low acoustic pressures. AB - Recent optical and acoustical studies have shown a threshold behaviour in the response of phospholipid-coated contrast agents, for a certain range of sizes. Below the acoustic pressure threshold, the microbubbles' scattering efficacy is significantly reduced compared to that above the threshold. Here we investigate the clinical relevance of the observed threshold behaviour. A cardiac ultrasound scanner system was used to analyse the pressure-dependence of the scatter intensity. The scattering of a native suspension of a phospholipid-coated contrast agent was compared to that of a suspension in which microbubbles with a size larger than 3.0 microm in diameter were extracted. A power modulation scheme at the fundamental frequency was applied. After linearly scaling and subtracting the B-mode images recorded at 70 and 200 kPa, the contrast-to-tissue ratio (CTR) of the native suspension was 3.2dB, whereas the CTR of the filtered suspension was 20 dB. The 17 dB difference is attributed to the threshold behaviour. Well established ultrasound imaging techniques such as fundamental power modulation imaging could benefit from the pressure-dependent scattering properties of this type of contrast microbubbles. PMID- 17845811 TI - Ocular aberrations in barn owl eyes. AB - Optical quality in barn owl eyes is presented in terms of measuring the ocular wavefront aberrations with a standard Tscherning-type wavefront aberrometer under natural viewing conditions. While accommodative state was uncontrolled, all eyes were focused within 0.4D with respect to the plane of the aberrometer. Total RMS wavefront error was between 0.06 and 0.15 microm (mean: 0.10 microm, STD: 0.03 microm, defocus cancelled) for a 6 mm pupil. The results suggest that image quality in barn owl eyes is excellent. PMID- 17845810 TI - Developmental changes in the visual span for reading. AB - The visual span for reading refers to the range of letters, formatted as in text, that can be recognized reliably without moving the eyes. It is likely that the size of the visual span is determined primarily by characteristics of early visual processing. It has been hypothesized that the size of the visual span imposes a fundamental limit on reading speed [Legge, G. E., Mansfield, J. S., & Chung, S. T. L. (2001). Psychophysics of reading. XX. Linking letter recognition to reading speed in central and peripheral vision. Vision Research, 41, 725-734]. The goal of the present study was to investigate developmental changes in the size of the visual span in school-age children and the potential impact of these changes on children's reading speed. The study design included groups of 10 children in 3rd, 5th, and 7th grade, and 10 adults. Visual span profiles were measured by asking participants to recognize letters in trigrams (random strings of three letters) flashed for 100ms at varying letter positions left and right of the fixation point. Two print sizes (0.25 degrees and 1.0 degrees ) were used. Over a block of trials, a profile was built up showing letter recognition accuracy (% correct) versus letter position. The area under this profile was defined to be the size of the visual span. Reading speed was measured in two ways: with Rapid Serial Visual Presentation (RSVP) and with short blocks of text (termed Flashcard presentation). Consistent with our prediction, we found that the size of the visual span increased linearly with grade level and it was significantly correlated with reading speed for both presentation methods. Regression analysis using the size of the visual span as a predictor indicated that 34-52% of variability in reading speeds can be accounted for by the size of the visual span. These findings are consistent with a significant role of early visual processing in the development of reading skills. PMID- 17845812 TI - Genotoxic evaluation of two mercury compounds in the Drosophila wing spot test. AB - Few studies on the genotoxicity of mercury compounds have been carried out in Drosophila melanogaster, most of them focused in the effects on germinal cells, whereas studies in somatic cells are scarce. In the present study we have analyzed for the first time the genotoxic activity of mercury (II) chloride (MC) and methyl mercury (II) chloride (MMC) in the in vivo wing somatic mutation and recombination test in Drosophila, also known as the wing spot assay. This test is based on the principle that loss of heterozygosis and the corresponding expression of the suitable recessive markers, multiple wing hairs (mwh) and flare 3 (flr(3)), can lead to the formation of mutant clones in larval cells, which are then expressed as spots on the wings of adult flies. The mercury compounds were supplied to third instar larvae (72+/-2h old) at concentrations ranging from 1 to 50 microM for mercury chloride (MC) and from 0.5 to 5 microM for methyl mercury chloride (MMC). Both mercury compounds showed high toxicity; however, MMC was more toxic than MC. The results showed that none of the three categories of mutant spots recorded (small, large, and twin) increased significantly by the treatments, independently of the dose supplied, indicating that the mercury compounds tested exhibit a lack of genotoxic activity in the wing spot assay of D. melanogaster. These results contribute to increase the genotoxicity database on the in vivo evaluation of mercury compounds in Drosophila. PMID- 17845813 TI - Influence of a soil enzyme on iron-cyanide complex speciation and mineral adsorption. AB - Cyanide is commonly found as ferrocyanide [Fe(II)(CN)(6)](-4) and in the more mobile form, ferricyanide [Fe(III)(CN)(6)](-3) in contaminated soils and sediments. Although soil minerals may influence ferrocyanide speciation, and thus mobility, the possible influence of soil enzymes has not been examined. In a series of experiments conducted under a range of soil-like conditions, laccase, a phenoloxidase enzyme derived from the fungi Trametes versicolor, was found to exert a large influence on iron-cyanide speciation and mobility. In the presence of laccase, up to 93% of ferrocyanide (36-362ppm) was oxidized to ferricyanide within 4h. No significant effect of pH (3.6 and 6.2) or initial ferrocyanide concentration on the extent or rate of oxidation was found and ferrocyanide oxidation did not occur in the absence of laccase. Relative to iron-cyanide mineral systems without laccase, ferrocyanide adsorption to aluminum hydroxide and montmorillonite decreased in the presence of laccase and was similar to or somewhat greater than that of ferricyanide without laccase. Laccase-catalyzed conversion of ferrocyanide to ferricyanide was extensive though up to 33% of the enzyme was mineral-bound. These results demonstrate that soil enzymes can play a major role in ferrocyanide speciation and mobility. Biotic soil components must be considered as highly effective oxidation catalysts that may alter the mobility of metals and metal complexes in soil. Immobilized enzymes should also be considered for use in soil metal remediation efforts. PMID- 17845814 TI - Growth assays with mixed cultures of cyanobacteria and algae assessed by in vivo fluorescence: One step closer to real ecosystems? AB - A growth toxicity assay with mixed cultures of cyanobacteria and algae using in vivo fluorescence is presented. Test organisms (the green alga Pseudokirchneriella subcapitata and the cyanobacterium Aphanothece clathrata) growing alone and in a mixture were exposed to selected chemicals. P. subcapitata featured a higher sensitivity to toxicants in the presence of A. clathrata compared to the single species assay. On the other hand, growth of a cyanobacterium was not affected by the presence or absence of the green alga. The proposed method seems to be suitable for pre-screening studies of toxicants (algistatic agents, herbicides) applied into the aquatic environment and for the assessment of their impact on natural phytoplankton communities. PMID- 17845815 TI - Experimental and modeling study of the effect of CO and H2 on the urea DeNO(x) process in a 150kW laboratory reactor. AB - An experimental and modeling investigation has been performed to study the effect of process additives, H2 and CO on NO(x) removal from flue gases by a selective non-catalytic reduction process using urea as a reducing agent. Experiments were performed with a flow reactor in which flue gas was generated by the combustion of propane in air at 3% excess oxygen and the desired levels of initial NO(x) (500ppm) were achieved by doping the flame with ammonia. Experiments were performed throughout the temperature range of interest, i.e. from 850 to 1200 degrees C for investigation of the effects of the process additives on the performance of aqueous urea DeNO(x). Subsequently, computational kinetic modeling with SENKIN code was performed to analyze the performance of urea providing a direct comparison of modeling prediction with experimental measurements. With CO addition, a downwards shift of 215 degrees C in the peak reduction temperature from 1125 to 910 degrees C was observed during the experimentation while the kinetic modeling suggests it to be 150 degrees C, i.e. from 1020 to 870 degrees C. The addition of H2 impairs the peak NO(x) reduction but suggests a low temperature application of the process. A downward shift of 250 degrees C in the peak reduction temperature, from 1020 to 770 degrees C, was observed during kinetic modeling studies. The kinetic modeling shows a good qualitative agreement with the experimental observations and reveals additional information about the process. PMID- 17845816 TI - Rapid decline of persistent organochlorine pollutants in serum among young Swedish males. AB - To investigate a possible time trend in serum concentrations of persistent organochlorine pollutants (POPs), representative samples of the young (median age 18 years) Swedish male population were investigated in the years 2000 and 2004. Due to their low age, these men were assumed not to have reached steady state of body burdens of POPs, why their serum concentrations were considered to represent ongoing dietary exposure. Serum concentrations of 2,2',4,4',5,5' hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(4-chlorophenyl)-ethylene (p,p'-DDE), two biomarkers of exposure to POPs, were available for 274 and 223 men, respectively, in 2000 and for 200 men in 2004. The percentage of men with CB 153 or p,p'-DDE below the limit of detection (LOD) was significantly higher in 2004 than in 2000 (30% vs. none, p < 0.001 for CB-153 and 65% vs. 6%, p < 0.001 for p,p'-DDE). Moreover, the median serum concentration of CB-153 decreased from 66 ng g(-1) lipid to 19 ng g(-1), corresponding to a yearly decrease of about 26%. The analogous analysis was not done for p,p'-DDE since the median serum concentration in 2004 was below the LOD. PMID- 17845817 TI - Analysis of subcritical crack growth in dental ceramics using fracture mechanics and fractography. AB - OBJECTIVES: The aim of this study was to test the hypothesis that the flexural strengths and critical flaw sizes of dental ceramic specimens will be affected by the testing environment and stressing rate even though their fracture toughness values will remain the same. METHODS: Ceramic specimens were prepared from an aluminous porcelain (Vitadur Alpha; VITA Zahnfabrik, Bad Sackingen, Germany) and an alumina-zirconia-glass composite (In-Ceram Zirconia; VITA Zahnfabrik). Three hundred uniaxial flexure specimens (150 of each material) were fabricated to dimensions of 25 mmx4 mmx1.2 mm according to the ISO 6872 standard. Each group of 30 specimens was fractured in water using one of four different target stressing rates ranging on a logarithmic scale from 0.1 to 100 MPa/s for Vitadur Alpha and from 0.01 to 10 MPa/s for In-Ceram Zirconia. The fifth group was tested in inert environment (oil) with a target stressing rate of 100 MPa/s for Vitadur Alpha and 1000 MPa/s for In-Ceram Zirconia. The effects of stressing rate and environment on flexural strength, critical flaw size, and fracture toughness were analyzed statistically by Kruskal-Wallis one-way ANOVA on ranks followed by post hoc comparisons using Dunn's test (alpha=0.05). In addition, 20 Vitadur Alpha specimens were fabricated with controlled flaws to simplify fractography. Half of these specimens were fracture tested in water and half in oil at a target stressing rate of 100 MPa/s, and the results were compared using Mann-Whitney rank sum tests (alpha=0.05). A logarithmic regression model was used to determine the fatigue parameters for each material. RESULTS: For each ceramic composition, specimens tested in oil had significantly higher strength (P0.05). Specimens tested at faster stressing rates had significantly higher strength (P0.05). Regarding critical flaw size, stressing rate had a significant effect for In Ceram Zirconia specimens (P0.05). Fatigue parameters, n and lnB, were 38.4 and -12.7 for Vitadur Alpha and were 13.1 and 10.4 for In-Ceram Zirconia. SIGNIFICANCE: Moisture assisted subcritical crack growth had a more deleterious effect on In-Ceram Zirconia core ceramic than on Vitadur Alpha porcelain. Fracture surface analysis identified fracture surface features that can potentially mislead investigators into misidentifying the critical flaw. PMID- 17845818 TI - Conformations generated during turnover of the Azotobacter vinelandii nitrogenase MoFe protein and their relationship to physiological function. AB - Various S=3/2 EPR signals elicited from wild-type and variant Azotobacter vinelandii nitrogenase MoFe proteins appear to reflect different conformations assumed by the FeMo-cofactor with different protonation states. To determine whether these presumed changes in protonation and conformation reflect catalytic capacity, the responses (particularly to changes in electron flux) of the alphaH195Q, alphaH195N, and alphaQ191K variant MoFe proteins (where His at position 195 in the alpha subunit is replaced by Gln/Asn or Gln at position alpha 191 by Lys), which have strikingly different substrate-reduction properties, were studied by stopped-flow or rapid-freeze techniques. Rapid-freeze EPR at low electron flux (at 3-fold molar excess of wild-type Fe protein) elicited two transient FeMo-cofactor-based EPR signals within 1 s of initiating turnover under N(2) with the alphaH195Q and alphaH195N variants, but not with the alphaQ191K variant. No EPR signals attributable to P cluster oxidation were observed for any of the variants under these conditions. Furthermore, during turnover at low electron flux with the wild-type, alphaH195Q or alphaH195N MoFe protein, the longer-time 430-nm absorbance increase, which likely reflects P cluster oxidation, was also not observed (by stopped-flow spectrophotometry); it did, however, occur for all three MoFe proteins under higher electron flux. No 430-nm absorbance increase occurred with the alphaQ191K variant, not even at higher electron flux. This putative lack of involvement of the P cluster in electron transfer at low electron flux was confirmed by rapid-freeze (57)Fe Mossbauer spectroscopy, which clearly showed FeMo-factor reduction without P cluster oxidation. Because the wild-type, alphaH195Q and alphaH195N MoFe proteins can bind N(2), but alphaQ195K cannot, these results suggest that P cluster oxidation occurs only under high electron flux as required for N(2) reduction. PMID- 17845819 TI - Carnosine as molecular probe for sensitive detection of Cu(II) ions using localized 1H NMR spectroscopy. AB - Complex formation of carnosine (Csn) with Cu(II) is suspected to be of significant biochemical importance and can be detected by NMR via ion-induced paramagnetic relaxation of Csn signals. Here, we present quantification of the sensitivity achieved with localized (1)H NMR spectroscopy at physiological pH and high ligand-to-metal ratios. While characterizing the highly effective relaxation transfer onto a huge Csn pool due to fast ligand exchange, it is demonstrated that a metal-to-ligand ratio of approximately 100 ppm suffices to reduce Csn signals by approximately 50% in vitro, thus making the dipeptide a sensitive probe for such ions. Variation of the donor accessibility reveals that the paramagnetic effect is transferred onto a approximately 1370-fold donor abundance for a given ion concentration. A method is presented to characterize such effective ligand exchange relaxation transfer. These studies focus on the monomer formation since comparison with (1)H NMR data of human calf muscle demonstrates that the dimer complex is insignificant in vivo. Observed line broadening in living tissue yields an upper limit of ca. 195 ppm for the Csn-related copper concentration in human skeletal muscle. PMID- 17845820 TI - Effect of peripheral trifluoromethyl groups in artificial iron porphycene cofactor on ligand binding properties of myoglobin. AB - An iron porphycene, a structural isomer of iron porphyrin, with trifluoromethyl groups at the peripheral position of the framework was incorporated into sperm whale apomyoglobin. The prepared myoglobin shows the higher O(2) affinity than the native protein. However, the oxygen affinity of the reconstituted myoglobin is lower than that of the myoglobin having an iron porphycene without trifluoromethyl groups, which is mainly originated from the enhancement of the O(2) dissociation. The CO affinity of the myoglobin with the trifluoromethylated iron porphycene is similar to that observed for the reference protein having the iron porphycene without trifluoromethyl groups, although their C-O stretching frequencies are significantly different. The relationship between the electronic states of the porphycene ring and the ligand bindings is discussed. PMID- 17845822 TI - The category of 1:1 ratio caused by assimilation of two neighboring empty time intervals. AB - We investigated the perception of temporal patterns of two neighboring empty time intervals, t1 and t2, in this order. In a previous study, we reported that bilateral assimilation took place during t1 and t2, as well as unilateral assimilation. [Miyauchi, R. & Nakajima, Y. (2005). Bilateral assimilation of two neighboring empty time intervals. Music Perception, 22, 411-424]. The points of subjective equality (PSEs) of t1 and t2 approached each other. We speculated that these temporal patterns would yield nearly 1:1 ratios perceptually despite the change in the physical temporal ratio between t1 and t2. However, we were uncertain whether these temporal patterns were really perceived as having 1:1 ratios. In the present study, we conducted three experiments. In Experiment 1, we measured subjective similarities of two temporal patterns and analyzed the results by hierarchical cluster analysis and multidimensional scaling. The temporal patterns, where the physical ratio between t1 and t2 was varied systematically, were divided into three clusters, and one cluster consisted of the temporal patterns within a range of -80 ms 100 can be obtained. When SiO(2)/Al(2)O(3) or=11 points in the Yesavage's scale was used for defining depressive symptoms, and hypomagnesemia was defined by serum magnesium levels <0.74 mmol/L. Well-known causes for depression as well as diseases and drugs that may cause depressive symptoms or hypomagnesemia were exclusion criteria. RESULTS: Serum magnesium levels were significantly lower among depressive than control diabetic subjects (0.74 +/- 0.25 vs. 0.86 +/- 0.29 mmol/L, p = 0.02). Twenty four (43.6%) and 7 (12.7%) individuals in the case and control group exhibited low serum magnesium levels (p = 0.0006). The adjusted logistic regression analysis showed an independent association between hypomagnesemia and depressive symptoms (OR 1.79; CI(95%) 1.1-6.9, p = 0.03). CONCLUSIONS: Our results suggest that hypomagnesemia is independently associated with depressive symptoms in older people with diabetes. PMID- 17845895 TI - Plasma protein lipofuscin-like fluorophores in men with coronary artery disease treated with statins. AB - BACKGROUND: Lipid oxidation products react with protein to produce lipofuscin like fluorophores (P-LLF) and modified apolipoprotein B that is an important element of the atherogenic properties of oxidized low-density lipoprotein (oxLDL). The aim of this study was to compare plasma concentrations of P-LLF between men with coronary artery disease (CAD) treated with statin drugs and healthy controls and to identify determinants of P-LLF. METHODS: Plasma markers of protein modification including P-LLF and oxidized low-density lipoprotein-4E6 (oxLDL-4E6), low-density lipoprotein-conjugated dienes (LDL-CD), lipid peroxides, apolipoprotein B, and serum albumin were measured in 24 men with CAD who were receiving statin therapy and 20 healthy men in the same age range. RESULTS: Plasma P-LLF (+23%, p = 0.001) was significantly higher and plasma oxLDL-4E6 ( 33%, p <0.001) and apolipoprotein B (apoB) (-30%, p <0.001) concentrations were significantly lower in men with CAD compared with controls. Plasma P-LLF concentration was correlated significantly with plasma apoB (r = -0.596, p <0.001), serum albumin (r = 0.518, p <0.001), and age (r = 0.390, p = 0.009) and these variables were independent predictors of P-LLF in the study population. Plasma P-LLF was no longer significantly higher in men with CAD when plasma apoB concentration was taken into account. CONCLUSIONS: Plasma P-LLF concentration is abnormally high and appears to be closely associated with lower levels of apoB in men with CAD receiving statin therapy. ApoB may be a preferential target of reactive aldehydic lipid oxidation products and a decrease in apoB may increase the quantity of these products available for condensation with albumin. PMID- 17845896 TI - Vascular endothelial growth factor immunostaining correlates with postoperative relapse and survival in non-small cell lung cancer. AB - BACKGROUND: Angiogenesis is an early step in tumor progression, and vascular endothelial growth factor (VEGF) is an important angiogenic factor. In this study, we investigated the prognostic significance of VEGF immunostaining in tumor tissues of non-small cell lung cancer (NSCLC) patients during a 5-year follow-up period. METHODS: The study comprised 50 male patients diagnosed with NSCLC with a mean age of 57.26 +/- 8.64 years (range: 40-74 years). All patients had early stage NSCLC and none of the patients received chemo- or radiation therapy before surgery. VEGF immunostaining was performed in tumor tissues and immunoreactivity was graded as negative (0-10%), weak (10-50%), and strong (>50% tumors are stained). RESULTS: VEGF staining was weak in 20 (40%) specimens and strong in 13 (26%) specimens, whereas VEGF staining was negative in 17 (34%) specimens. Strong VEGF staining showed a significant correlation with both short time of relapse (p = 0.0001) and short survival (p = 0.0005). Multivariate analysis using Cox regression model was performed to determine the independent prognostic factors. Age (p = 0.029, OR: 1.05), tumor stage (p = 0.001, OR: 14.89), and VEGF staining (p = 0.006, OR: 4.65) were all found as independent prognostic factors in NSCLC. CONCLUSIONS: Strong VEGF immunostaining in tumor tissues was found to be an important prognostic factor for time to relapse and survival in patients with early stage disease. PMID- 17845897 TI - Clinical and molecular parameters for risk stratification in Mexican children with medulloblastoma. AB - BACKGROUND: Clinical, histological, and more recently, molecular factors have been described as important in survival of the patient with medulloblastoma. Best survival results include aggressive chemotherapeutic protocols. More exact risk analysis may differentiate patients who require aggressive treatments from those with low risk who may respond adequately to less aggressive protocols. METHODS: Twenty six patients were included over a 10-year period and were followed for at least 5 years. Personal variables were obtained from their clinical records. Immunochemistry studies were performed on their formalin-fixed paraffin-embedded tissues. Statistical analysis included chi(2) test, odds risk, linear regression models, and Kaplan-Meier survival analysis. RESULTS: Metastatic disease and chemotherapy with VP16-carboplatin reduce the patient's probability of survival, whereas anaplastic histology increases the probability of death. Global survival and disease-free survival were 66.6 and 45.02%, respectively. Only two patients overexpressed the ERBB2 protein, and no significant difference was found in survival in terms of ERBB2 overexpression. CONCLUSIONS: Risk stratification has become very important in medulloblastoma. We found an increased hazard of death when metastatic disease was present. Gene expression in Mexican children requires a larger sample in order to be analyzed. PMID- 17845898 TI - Herpes simplex virus type 2 among Mexican high school adolescents: prevalence and association with community characteristics. AB - BACKGROUND: We undertook this study to estimate the prevalence and correlates of herpes simplex virus type 2 (HSV-2) among Mexican adolescents in high school. METHODS: This was a cross-sectional analysis using data that had been collected to evaluate a school-based HIV prevention intervention. As part of the final round of evaluation, capillary blood samples were taken from volunteers to test for antibodies to HSV-2. The effect of each school's seroprevalence on the probability of an individual being seropositive was estimated, and the results were grouped by town to evaluate the association between characteristics of the locality and student HSV-2 seroprevalence. RESULTS: Dried blood spots were collected for 80% of the 1607 participants in the survey who reported that they were sexually active. Of these samples, 21% tested positive for HSV-2 antibodies, with no significant difference in prevalence between men and women. Seroprevalence among schools ranged from 0 to 57%. The number of sex workers registered in the locality was the most important covariate of seroprevalence, with each additional female sex worker (FSW) per 1000 women between 18 and 45 years of age in the town associated with an increase of 1% in the seroprevalence of HSV-2. CONCLUSIONS: Characteristics of adolescents' micro-environments that influence their pool of potential sexual partners and the likelihood that these partners are HSV-2 positive may be more important predictors of the risk of STI infection than self-reported condom use. PMID- 17845899 TI - Metabolic syndrome and C-reactive protein among cardiology patients. AB - BACKGROUND: Associations between inflammation, metabolic syndrome (MetS), and cardiovascular disease have been reported. Limited information, however, is available on the prevalence of MetS and its relation to inflammation among Georgian cardiology patients. We investigated MetS components (elevated blood pressure, abdominal obesity, elevated triglyceride concentrations, decreased HDL cholesterol concentrations, and elevated fasting glucose) and their relationships with C-reactive protein (CRP) concentrations in this population. METHODS: A total of 167 patients (mean age 53.1 years, 54% male) who attended an Emergency Cardiology Center in Tbilisi, Republic of Georgia were enrolled in this cross sectional study. In-person interviews and clinical exams, as well as laboratory studies, were conducted to characterize MetS (using the ATP III criteria) and cardiac conditions in the study population. CRP concentrations were determined using standardized immunoassays. RESULTS: Overall prevalence of MetS was 40.7%. Patients with coronary heart disease (CHD) had higher CRP concentrations compared with non-CHD patients. A linear relationship between increase in number of MetS components and CRP concentrations was observed among females (p value for linear trend <0.05), but not males. Further, among females, all components of MetS except HDL-C concentrations were correlated with CRP concentrations after adjustment for age and body mass index (all p values <0.05). However, among males, only abdominal obesity was significantly correlated with CRP. CONCLUSIONS: MetS is prevalent among Georgian cardiology patients. CRP concentrations are positively associated with MetS. Further prospective studies are required to determine whether combining MetS and CRP data may have utility in the assessment of risk for developing future cardiovascular events in both males and females. PMID- 17845900 TI - Inhibition of corneal neovascularization with a nutrient mixture containing lysine, proline, ascorbic acid, and green tea extract. AB - Corneal neovascularization is a significant, sight-threatening complication of many ocular surface disorders. Various growth factors and proteinases are involved in corneal neovascularization. The data supporting a causal role for vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are extensive. Inhibition of VEGF and MMPs is a main strategy for treating corneal neovascularization. Several findings have shown that corneal neovascularization can be reduced by using anti-VEGF and anti-MMPs agents. Efficacy of a nutrient mixture (NM) containing lysine, proline, ascorbic acid, and green tea extract has been demonstrated for reducing VEGF and MMPs secretion by various cells. Moreover, NM can inhibit endothelial cell migration and capillary tube formation. We herein note that topical application of NM is potentially useful for inhibiting corneal neovascularization and restoration of corneal clarity. Further investigations in animal models are needed to place NM alongside corneal neovascularization therapeutics. PMID- 17845901 TI - Alloimmune neonatal neutropenia due to anti-HNA-2a alloimmunization with severe and prolonged neutropenia but mild clinical course: two case reports. AB - Alloimmunization to granulocyte-specific antigens can occur during pregnancy. Maternal IgG can cross the placenta and result in neonatal neutropenia. The clinical course of alloimmune neonatal neutropenia is usually self-limiting with only mild infection. However, in severe cases complicated with bacterial sepsis it is a potentially life-threatening disorder. The effect of intravenous (IV) immunoglobulin, prophylactic antibiotic therapy, and recombinant human granulocyte-colony stimulating factor is variable and may prove useful in some cases. Two cases of alloimmune neonatal neutropenia due to anti HNA-2a alloimmunization in two siblings are reported. The first neonate was administered IV gammaglobulins to increase the blood neutrophil count, at a standard dosage (0.4 g/kg body weight) for 5 days without response. The second neonate did not receive specific therapy for blood neutrophil count increase. Neutropenia persisted for 2 and 6 months, respectively. The choice and efficacy of specific therapy for neutrophil count increase in the management of alloimmune neonatal neutropenia have not yet been fully defined and require additional evaluation in the majority of cases. PMID- 17845902 TI - Trisomy 21 as a sole acquired abnormality in an adult Omani patient with CD7- and CD9-positive acute myeloid leukemia. AB - We describe a case of acute myeloid leukemia (AML) in which trisomy 21 was the sole acquired cytogenetic abnormality. The immunophenotype showed positivity for CD7 and CD9 along with CD13, CD33, and CD34. The chromosomal analysis of bone marrow showed 47,XY +21 in all the metaphases analyzed. The constitutional karyotype was normal. The patient was an adult and did not have any features of Down's syndrome. The bone marrow morphology was AML-M2 as per the French-American British (FAB) criteria. A final diagnosis of CD7- and CD9-positive AML-M2 was established with trisomy 21 as a sole cytogenetic abnormality. The patient responded remarkably well to chemotherapy and achieved complete clinical remission. This is the first case of CD7- and CD9-positive AML with trisomy 21 as a sole abnormality. A putative role for the co-expression of abnormal lymphoid markers in achieving quick remission is discussed. PMID- 17845903 TI - Use of D11S2179 and D11S1343 as markers for prenatal diagnosis of ataxia telangiectasia in Iranian patients. AB - Ataxia telangiectasia (AT) is an autosomal recessive disorder with an estimated prevalence of 1/40,000 to 1/100,000 in reported populations. There is a 25% possibility for having an affected child when parents are carriers for the ATM gene mutation. There is no cure available for this disease and prenatal testing is strongly recommended for prevention of this disease. Although the preferred method is the direct mutation analysis of the ATM gene, the large size of the ATM gene with 63 exons and the large number of possible mutations in patients considerably limit efficiency of mutation analysis as a diagnostic choice. Indirect method is a better tool when parents are not carriers of founder mutation and pass different mutations to their children. Indirect molecular diagnosis using ATM-related molecular markers facilitates prenatal diagnosis of AT children. In this study, four molecular markers: D11S2179, D11S1787, D11S535, D11S1343 are genotyped in 19 unrelated families from different regions of Iran. Those markers are amplified using extracted sequence primers from the Gene Bank with their described PCR conditions. Amplified products were separated using denaturing PAGE gels, and data were analyzed to detect their pattern of inheritance in each family. In all families, segregation of alleles was according to Mendelian inheritance, and affected chromosomes were distinguishable from unaffected ones. All carriers and affected patients were diagnosed accurately. Thus, this method is effectively useful in prenatal diagnosis of AT. PMID- 17845904 TI - Reticulospinal neurons in anamniotic vertebrates: a celebration of Alberto Stefanelli's contributions to comparative neuroscience. AB - Over the past 76 years Alberto Stefanelli has successfully used a comparative approach to study the nervous system. His main research focus during that time has been on identifiable reticulospinal neurons including Muller and Mauthner neurons found in anamniotic vertebrates. Born in Venice, Italy in 1908, Professor Stefanelli pursued most of his academic career at the University of Rome, where he retired as Chair of Comparative Anatomy in 1978. His seminal work on the constancy in number and position of giant identifiable reticulospinal neurons in the brains of larval and adult lampreys, and his assertion that only a subset of these neurons were Muller cells, provided the framework in which subsequent authors have refined our understanding of the cellular anatomy, axonal projections, physiology, and function of Muller cells in the control of movement. Stefanelli has also provided the most comprehensive study to date of the Mauthner cell and its axon cap. His description of the differences in axon cap structure among many fishes and amphibians and his use of the "morpho-ecological" approach to determine Mauthner cell function has provided the basis for future studies on the neuronal basis of behavior and its evolution. As Professor Stefanelli approaches his 100th birthday, we celebrate his scientific contributions to comparative neuroscience with a biographical sketch of his life, an overview of his scientific accomplishments, and our view of how his comparative studies continue to contribute to our understanding of the nervous system. PMID- 17845905 TI - FTY720 sustains and restores neuronal function in the DA rat model of MOG-induced experimental autoimmune encephalomyelitis. AB - FTY720 (fingolimod) is an oral sphingosine 1-phosphate (S1P) receptor modulator under development for the treatment of multiple sclerosis (MS). To elucidate its effects in the central nervous system (CNS), we compared functional parameters of nerve conductance in the DA rat model of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) after preventive and therapeutic treatment. We demonstrate that prophylactic therapy protected against the emergence of EAE symptoms, neuropathology, and disturbances to visual and somatosensory evoked potentials (VEP, SEP). Moreover, therapeutic treatment from day 25 to 45 markedly reversed paralysis in established EAE and normalized the electrophysiological responses, correlating with decreased demyelination in the brain and spinal cord. The effectiveness of FTY720 in this model is likely due to several contributing factors. Evidence thus far supports its role in the reduction of inflammation and preservation of blood-brain-barrier integrity. FTY720 may also act via S1P receptors in glial cells to promote endogenous repair mechanisms that complement its immunomodulatory action. PMID- 17845906 TI - Potential of PSA-NCAM in neuron-glial plasticity in the adult hypothalamus: role of noradrenergic and GABAergic neurotransmitters. AB - The present study was designed to establish the dynamic regulation of polysialylated form of neural cell adhesion molecule (PSA-NCAM) expression by neurotransmitters controlling gonadotropin releasing hormone (GnRH) secretion. The expression of PSA-NCAM and glial fibrillary acidic protein (GFAP) on GnRH cell bodies and axon terminals in the medial preoptic area (mPOA) and median eminence-arcuate (ME-ARC) region of hypothalamus was studied in the proestrous phase of cycling rats treated with alpha-adrenergic receptor blocker phenoxybenzamine (PBZ) and gamma-aminobutyric acid (GABA) by using dual immunohistofluorescent staining and Western blot hybridization. To further elucidate whether activity mediated regulation of PSA-NCAM in GnRH neuron is via regulation of PSA biosynthesis by polysialytransferase (PST) enzyme, the expression of PST-1 enzyme was studied by using fluorescent in situ hybridization (FISH). Both GnRH and PSA-NCAM immunostaining was much higher in the mPOA and ME ARC region from proestrous phase rats, whereas, PBZ and GABA treatments significantly reduced their expression, GFAP-ir and its content were increased in the PBZ and GABA treated proestrous rats. Taken together, our observations add to the growing evidence that PSA-NCAM plays permissive role for neuronal-glial remodeling and further suggest a functional link between activity dependent structural remodeling in GnRH neurons. Further, enhanced mRNA expression of PST suggests that the biosynthesis of PSA on NCAM is regulated at the transcriptional level. PMID- 17845907 TI - Differential response of apoptosis-regulatory Bcl-2 and Bax proteins to an inflammatory challenge in the cerebral cortex and hippocampus of aging mice. AB - Apoptosis plays a key role in normal aging and neurodegeneration. It is now known that normal aging implies low-grade inflammation and increases susceptibility to neurodegenerative diseases, which, in turn, include a neuroinflammatory component. We here investigated, using mice of 2-3 months, 10-11 months, or 18-21 months of age, the expression of apoptosis-regulatory proteins in cortical brain regions in response to intracerebroventricular administration of pro-inflammatory cytokines. A mixture of interferon-gamma and tumor necrosis factor-alpha was injected, using vehicle (phosphate-buffered saline) as control. At 4 days, levels of the anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins in the cerebral cortex and hippocampus, examined with Western blotting, were markedly upregulated by cytokine exposure in mice of all age groups with respect to controls. Interestingly, cytokine-elicited Bcl-2 upregulation was aging-dependent, with significant enhancement paralleling the animals' age. Cytokine-elicited Bax expression did not exhibit instead significant aging-related variation. Using the same paradigm and 1 or 2 day survival, Bcl-2 immunoreactivity was observed mainly in neurons of cortex and hippocampus of both control and cytokine-treated mice of all age groups. Furthermore, immunohistochemistry confirmed the enhancement of cytokine-elicited Bcl-2 expression in the cerebral cortex and hippocampus of old mice, and showed that this finding was already evident in the second day after cytokine exposure. The data point out the novel finding that Bcl-2 and Bax expression in cortical brain regions is differentially regulated during senescence in response to an acute inflammatory challenge. Aging-related Bcl-2 increases in neurons after cytokine exposure could contribute to amplify neuroprotective mechanisms in the old brain. PMID- 17845908 TI - Primary rat monocytes migrate through a BCEC-monolayer and express microglia markers at the basolateral side. AB - Monocytes are pluripotent cells of the immune system, circulate in the blood and cross the blood-brain barrier continuously through life. The aim of this study was to explore if primary rat monocytes can adhere and transmigrate at a monolayer of brain capillary endothelial cells (BCEC) and if the monocytes undergo differentiation toward a microglial phenotype at the basolateral side. Monocytes and as a control primary microglia were immunohistochemically stained with markers for CD68 (clone ED-1), CD11b (clone OX-42) or CD11c (clone 8A2). The primary rat monocytes (100,000 cells added) adhered at the BCEC-monolayer (approx. 1200 cells/well) within 30 min and migrated to the basolateral side within 18 h (approx. 40,000 cells/well). The transmigrated monocytes partly differentiated and expressed microglia-markers at the basolateral side. Tumor necrosis factor-alpha as well as conditioned medium derived from BCEC stimulated the differentiation of monocytes in culture. In conclusion, monocytes adhere and migrate through a BCEC-monolayer and express microglia-markers at the basolateral side. PMID- 17845909 TI - Processing the socially relevant parts of faces. AB - Faces are processed by a distributed neural system in the visual as well as in the non-visual cortex [the "core" and the "extended" systems, J.V. Haxby, E.A. Hoffman, M.I. Gobbini, The distributed human neural system for face perception, Trends Cogn. Sci. 4 (2000) 223-233]. Yet, the functions of the different brain regions included in the face processing system are far from clear. On the basis of the case study of a patient unable to recognize fearful faces, Adolphs et al. [R. Adolphs, F. Gosselin, T.W. Buchanan, D. Tranel, P. Schyns, A.R. Damasio, A mechanism for impaired fear recognition after amygdala damage, Nature 433 (2005) 68-72] suggested that the amygdala might play a role in orienting attention towards the eyes, i.e. towards the region of face conveying most information about fear. In a functional magnetic resonance (fMRI) study comparing patterns of activation during observation of whole faces and parts of faces displaying neutral expressions, we evaluated the neural systems for face processing when only partial information is provided, as well as those involved in processing two socially relevant facial areas (the eyes and the mouth). Twenty-four subjects were asked to perform a gender decision task on pictures showing whole faces, upper faces (eyes and eyebrows), and lower faces (mouth). Our results showed that the amygdala was activated more in response to the whole faces than to parts of faces, indicating that the amygdala is involved in orienting attention toward eye and mouth. Processing of parts of faces in isolation was found to activate other regions within both the "core" and the "extended" systems, as well as structures outside this network, thus suggesting that these structures are involved in building up the representation of the whole face from its parts. PMID- 17845910 TI - The maintenance of individual differences in the sensitivity of acute and neuropathic pain behaviors to electroacupuncture in rats. AB - "Responder" Sprague-Dawley (SD) rats that were sensitive to electroacupuncture (EA) in an acute thermal pain test (i.e. tail flick latency [TFL] test) maintained sensitivity to EA in the warm allodynia test after peripheral nerve injury. Similarly, the "non-responder" SD rats that were insensitive to EA in the TFL test were also insensitive to EA in the allodynia test. The EA-induced analgesic effects in the TFL test were significantly higher in CCK-A receptor deficient, Otsuka Long-Evans Tokushima Fatty (OLETF) rats than in their littermates, Long-Evans Tokushima Otsuka (LETO) rats. Similarly, the anti allodynic effects of EA were significantly greater in OLETF rats than in LETO rats. These results suggest that the individual differences in the sensitivity of acute pain behavior to EA were maintained in neuropathic pain behavior following peripheral nerve injury, and that CCK-A receptor expression plays an important role in mediating this phenomenon. PMID- 17845911 TI - The peri-electrode space is a significant element of the electrode-brain interface in deep brain stimulation: a computational study. AB - Deep brain stimulation (DBS) is an increasingly used clinical treatment for various neurological disorders, particularly movement disorders such as Parkinson's disease. However, the mechanism by which these high frequency electrical pulses act on neuronal activity is unclear. Once the stimulating electrode is placed in situ, an electrode-brain interface (EBI) is created. To compensate for the lack of studies on the effects of this generic depth EBI on therapeutic DBS, we constructed a three-dimensional computational model of the EBI using the finite element method, in which the structural details and biophysical properties of the EBI are preserved. Our investigations focus on the peri-electrode space as a significant element of the EBI, and its physiological and pathological modulation, in particular by brain pulsation and giant cell formation. We also consider the difference between the current fields induced by different configurations of the quadripolar electrode contacts. These results quantitatively demonstrated that the peri-electrode space is a significant element of the EBI and its biophysical properties are modulated by brain pulsation and giant cell formation, as well as by the choice of electrode contact configuration. This study leads to a fuller understanding of the EBI and its effects on the crossing electric currents, and will ultimately lead to optimisation of the therapeutic effects of DBS. PMID- 17845912 TI - DAMGO and 6beta-glycine substituted 14-O-methyloxymorphone but not morphine show peripheral, preemptive antinociception after systemic administration in a mouse visceral pain model and high intrinsic efficacy in the isolated rat vas deferens. AB - Peripheral micro-opioid receptors (MOR) have emerged as important components of inhibitory nociceptive pathways. Here, the antinociceptive effects of MOR agonists, the 6beta-glycine derivative of 14-O-methyloxymorphone (HS-731), DAMGO and morphine were evaluated in a mouse model of visceral pain. The abdominal acetic acid-induced writhing test was used to examine the peripheral, preemptive antinociceptive opioid action on visceral nociception. HS-731 administered subcutaneously (s.c.) or intracerebroventricularly (i.c.v.) dose-dependently and completely inhibited writhing, being 24-598-fold more potent, depending on the administration route, than two selective MOR agonists, the enkephalin analogue [D Ala(2),N-Me-Phe(4),Gly-ol(5)]enkephalin (DAMGO) and morphine. A longer duration of action (2-3 h) was induced by HS-731 given before acetic acid, while shorter effect was produced by morphine (30-60 min) and DAMGO (30-45 min). The antinociceptive effects of systemic opioids were reversed by the s.c. opioid antagonist, naloxone. Blocking of central MOR by the selective MOR antagonist D Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP, i.c.v.) resulted in a significant reduction of antinociception of s.c. morphine, whereas it completely failed to antagonize the effects of systemic HS-731 or DAMGO. In in vitro studies, HS-731 and DAMGO, but not morphine showed high intrinsic efficacy, naltrexone-sensitive agonist effect at MOR of the rat vas deferens. These data demonstrate that selective activation of peripheral MOR by systemic s.c. HS-731 or DAMGO produces potent peripheral, preemptive visceral antinociception, while morphine's effects are mediated primarily through central mechanisms. Our findings support the role of peripheral MOR in the pathology of pain states involving sensitization of peripheral nociceptors. PMID- 17845913 TI - Immunolocalization of muscarinic receptor subtypes in the reticular thalamic nucleus of rats. AB - In this study, to identify the precise localization of the muscarinic receptor subtypes m2, m3 and m4 in the rostral part of the rat reticular thalamic nucleus (rRt), namely, the limbic sector, we used receptor-subtype-specific antibodies and characterized the immunolabeled structures by light, confocal laser scanning, and electron microscopies. The m2-immunolabeling was preferentially distributed in the distal dendrite region where cholinergic afferent fibers tend to terminate and in the peripheral region of somata, whereas the m3-immunolabeling was more preferentially distributed in a large part of somata and in proximal dendrite shafts than in the distal dendrite region. Dual-immunofluorescence experiments demonstrated that majority of rRt neurons with parvalbumin immunoreactivity contain both m2 and m3. Neither m2 nor m3 was detected in presynaptic terminals or axonal elements. No m4-immunolabeling was detected in the rostral part of the thalamus including rRt. These results show the different distributions of m2 and m3 in rRt neurons, and strongly suggest that m2 is more closely associated with cholinergic afferents than m3. PMID- 17845914 TI - Sex differences in stroke evaluations in the Ischemic Stroke Genetics Study. AB - BACKGROUND: Epidemiologic studies suggest sex differences in evaluation of patients presenting with ischemic stroke. Sex differences in stroke evaluation could lead to sex differences in the validity of diagnosing ischemic stroke subtypes. This study assessed sex differences in the Ischemic Stroke Genetics Study (ISGS). METHODS: The ISGS is a prospective case-control genetic association study of patients with first-ever ischemic stroke at 5 US tertiary stroke centers. The diagnostic tests performed as part of medical care were recorded for each enrolled patient. RESULTS: A total of 505 patients were enrolled; 45% (229 of 505) were women and 55% (276 of 505) were men. Mean age at time of stroke was greater for women (66.6 v 61.9 years; P = .001). Frequency of brain computed tomography was 92% (254 of 276) for men and 90% (206 of 229) for women (P = .42). Magnetic resonance imaging was completed in 84% (232 of 276) of men and 83% (191 of 229) of women (P = .91). Frequency of electrocardiography was 91% (252 of 276) for men and 90% (206 of 229) for women (P = .60). Echocardiography was done in 74% (203 of 276) of men and 79% (180 of 229) of women (P = .19). Cervical arterial imaging occurred in 91% (208 of 229) of women and 86% (237 of 276) of men (P = .09). Intracranial vascular imaging was performed in 75% (207 of 276) of men and 79% (181 of 229) of women (P = .28). CONCLUSIONS: Our findings suggest no significant sex differences in the extent to which major diagnostic tests were performed in patients in ISGS. Dedicated tertiary stroke centers may reduce the sex bias in stroke evaluation that has been identified by previous studies. PMID- 17845915 TI - Relationship between the occurrence of spontaneous intracerebral hemorrhage and holidays and traditionally unlucky days in Fukuyama City, Hiroshima Prefecture, Japan. AB - To investigate whether calendrical information influences the occurrence of spontaneous intracerebral hemorrhage, we statistically compared the incidence of intracerebral hemorrhage for inpatients at Teraoka Memorial Hospital (164 patients), against various calendrical factors such as the day of the week, national holidays, and RokuYo (a recurring six-day series of lucky and unlucky days in the Japanese traditional calendar) over the period from January 1, 2001 to December 31, 2003. On Japanese national holidays the relative risk of intracerebral hemorrhage is significantly higher than on other days, certainly due to much more alcohol consumption on holidays. During RokuYo, the relative risk of intracerebral hemorrhage is extremely low on the traditionally unlucky days of ButsuMetsu and TomoBiki, as many Japanese people restrain their activities on these days. Certain days of the year and certain times of the Japanese supplemental calendars correlate significantly with the incidence of intracerebral hemorrhage. PMID- 17845916 TI - Clopidogrel-induced platelet inhibition cannot be detected by the platelet function analyzer-100 system in stroke patients. AB - The administration of an adenosine diphosphate (ADP) receptor antagonist, such as clopidogrel, is recommended for recurrent stroke patients under aspirin treatment. However, up to 25% of vascular patients have an inadequate response to clopidogrel treatment, which could be associated with increased reinfarction rates. This study investigated whether the platelet function analyzer (PFA-100) system represents an appropriate tool for monitoring clopidogrel's antiplatelet effects in stroke patients. Sixteen stroke patients on clopidogrel therapy (75 mg/day) were included in a prospective analyst-blinded, cross-sectional study. Platelet function was assayed by collagen/epinephrine (CEPI)- and collagen/ADP (CADP)-induced closure times (CTs) using the PFA-100 system. von Willebrand factor antigen (vWF-Ag) levels were measured by enzyme immunoassay. CEPI-CT and CADP-CT values averaged 160 +/- 15 seconds and 102 +/- 10 seconds, respectively, and were in the normal range. vWF-Ag concentrations averaged 153 +/- 17% and correlated inversely with CTs (r = .71; P < .002 for CEPI-CT, r = .54; P < .04 for CADP-CT). Our data indicate that the current PFA-100 cartridges are not sufficiently sensitive to detect clopidogrel-induced platelet inhibition in stroke patients. PMID- 17845917 TI - Evidence of the peripheral inflammatory response in patients with transient ischemic attack. AB - The peripheral inflammatory response, as a proxy for the acute-phase response (a known mechanism for ischemic preconditioning), and non-damage-producing transient ischemia must exist together in humans if this candidate mechanism confers ischemic tolerance. The present study was aimed at determining whether the peripheral inflammatory response (ie, elevated white blood cell, neutrophil, and monocyte counts) exists in transient ischemic attack (TIA) and stroke patients at the time of emergency room admission. The null hypothesis was tested for the variables of the peripheral inflammatory response between the mean of the laboratory normal population versus stroke and TIA patients. A retrospective review of 1041 medical records yielded 12 first-time TIA patients and 34 first time stroke patients with no confounding evidence of other inflammatory processes. In both groups, neutrophil and monocyte percentages were significantly higher than the laboratory means (in TIA cases: neutrophils, 67.9% [12.67%], P = .001; monocytes, 8.2% [2.7%], P = .020; in stroke cases: neutrophils, 64.9% [9.1%], monocytes, 7.7% [1.6%]; both P < .001). Absolute neutrophil count was significantly higher than the laboratory mean for the stroke cases (5.13 [1.88] K/UL; P = .022). Lymphocyte percentages and absolute lymphocyte count in both groups were significantly and abnormally lower than the laboratory mean (in TIA cases, 21.7% [10.5%] and 1.4 [0.6] K/UL, respectively; in stroke cases, 24.7% [8.4%] and 1.9 [0.7] K/UL, respectively; all P 10%) pediatric patients to accept donors for these patients without a prospective crossmatch between 1995 and 2005. A retrospective review of survival, rejection and infection was performed, comparing the frequency of rejection and infection in our patients who were transplanted with a complement-dependent cytotoxic (CDC)-positive donor/recipient crossmatch to those patients transplanted with a negative crossmatch. RESULTS: Thirteen of 17 patients were found to have a CDC-positive crossmatch. Actuarial survival after transplantation was 85% at 1 year and 73% at 3 years. Twelve of 13 (92%) of these patients experienced rejection, and 5 of 13 (38%) had recurrent rejection, generally in the first 2 months after transplantation. Rejection was associated with hemodynamic compromise in 58% of first rejection episodes and 67% of episodes of recurrent rejection. The frequency of rejection in these patients was significantly greater than the frequency in patients with a negative crossmatch in the first 6 months after transplantation, but not afterward. The frequency of infection episodes was not significantly different between the groups. CONCLUSIONS: Heart transplantation in pre-sensitized pediatric recipients with a CDC-positive donor/recipient crossmatch may result in reasonable short term survival, but with a high frequency of early rejection, often with hemodynamic compromise. PMID- 17845926 TI - Treatment of adenovirus pneumonia with cidofovir in pediatric lung transplant recipients. AB - BACKGROUND: Adenovirus pneumonia results in significant morbidity and mortality in lung transplant recipients. Cidofovir allows for directed therapy but can result in nephrotoxicity. We report our experience with cidofovir for the treatment of adenovirus pneumonia in pediatric lung transplant recipients. METHODS: In a retrospective review, we identified four cases of culture-proven adenovirus pneumonia in children who underwent lung transplantation at Texas Children's Hospital (TCH). All patients received cidofovir 1 mg/kg every other day or three times a week for a total of 4 weeks. Probenecid and intravenous hydration were administered in conjunction with the cidofovir. Intravenous immunoglobulin (IVIg) was given as adjunctive therapy, and immunosuppression was not modified during the treatment course. RESULTS: The four cases of adenovirus pneumonia comprised 4 of the 54 (7%) lung transplantations performed at TCH from 2002 to 2006, and all were in children <3 years of age. All patients developed pneumonia within 2 months after transplantation. With cidofovir treatment, three of the four children survived. Among the survivors, two developed early bronchiolitis obliterans within 1 year after transplant, and one has continued to have good graft function at 2 years after transplant. All patients maintained normal renal function throughout the treatment course. CONCLUSIONS: Pediatric lung transplant recipients <3 years of age are at increased risk of adenovirus pneumonia early after transplantation. Cidofovir, when used in the modified dosing regimen and in combination with IVIg and renal protection measures, is a safe and potentially effective treatment option for adenovirus pneumonia in lung transplant recipients. PMID- 17845927 TI - Post-operative infections in cystic fibrosis and non-cystic fibrosis patients after lung transplantation. AB - BACKGROUND: Cystic fibrosis (CF) lung disease is the major cause of mortality in CF patients. Lung transplantation remains a valid therapeutic option. It is unknown whether CF patients receiving healthy lungs have an equal susceptibility to infections when compared with non-CF lung transplant patients. Herein we present the largest analyses to date of the post-operative infection profiles of 60 CF and 60 non-CF lung transplant patients. METHODS: Bilateral allogeneic lung transplantations and post-transplant management were performed according to standard clinical procedures. Post-operative infections were diagnosed by conventional methods based on clinical symptoms and laboratory cultures. RESULTS: Sixty CF lung-transplant patients developed 278 post-operative respiratory infections, from which 307 pathogens were isolated. Pseudomonas aeruginosa predominantly occupied 60.3%, followed by Mycobacteria spp (7.2%), Aspergillus spp (5.9%) and Staphylococcus spp (5.5%). However, 60 non-CF transplant patients had 154 respiratory infections with 165 pathogens isolated. Pseudomonas aeruginosa was noted in 38.2%, followed by Aspergillus spp (9.7%), Staphylococcus spp (9.7%) and Mycobacteria spp (9.1%). The CF group demonstrated a significantly higher frequency of Pseudomonas respiratory infections than the non-CF group. Interestingly, no significant differences were detected in any infections from other systems including blood, sinuses, skin, wounds, oral cavity, bowel, eyes, peritoneal cavity and urinary tract. Moreover, the CF lung transplant patients had significantly less time free from Pseudomonas infections. CONCLUSIONS: The normal lungs implanted into CF patients had significantly higher susceptibility to Pseudomonas infections than those into non-CF patients, suggesting that defective innate immunity outside the lungs contributes to CF lung pathogenesis. PMID- 17845928 TI - Survival of patients with idiopathic pulmonary arterial hypertension after listing for transplantation: impact of iloprost and bosentan treatment. AB - BACKGROUND: Survival after idiopathic pulmonary arterial hypertension (IPAH) diagnosis is often shorter than the waiting time for grafts. Iloprost and bosentan improve outcome in advanced IPAH (New York Heart Association Functional Class III), but there is controversy about the limits of their efficacy in end stage (Class IV) IPAH. METHODS: We investigated the impact of iloprost (prostacyclin analog) and bosentan (endothelin-receptor antagonist) therapy on the outcome of patients with IPAH after listing for transplantation (Tx) to answer the following questions: (1) How efficient is this treatment in reducing mortality on waiting lists? (2) Is Tx still most promising for survival once recurrent right heart failure emerges, or can this treatment improve survival to an extent that exceeds post-Tx survival? We assessed the outcome of our IPAH patients listed for Tx between September 1996 and September 2005 in relation to kind and duration of medical treatment. RESULTS: Among 59 listed patients, 24 (40.7%) died before Tx, after 2.9 months (median). With iloprost and/or bosentan treatment the mortality on Tx lists was 33.3%, whereas with calcium-channel blockers it reached 64.3% (p < 0.05). Patients with iloprost and/or bosentan therapy showed similar survival, regardless of whether they responded to vasodilator testing. Survival after listing was better for patients who were transplanted than for those who received iloprost and/or bosentan but not Tx (p = 0.017). Iloprost and bosentan treatment allowed the withdrawal of 3 patients from Tx lists. CONCLUSIONS: Iloprost and bosentan allowed the effective bridge-to transplant treatment in IPAH. However, with this treatment the mortality rate on Tx lists remained high and survival benefit was lower than from transplantation. PMID- 17845929 TI - Clostridium difficile-associated diarrhea in heart transplant recipients: is hypogammaglobulinemia the answer? AB - BACKGROUND: Information regarding Clostridium difficile-associated diarrhea (CDAD) after solid-organ transplantation (SOT) is scarce, particularly after heart transplantation (HT). Although host immune response to C. difficile plays a substantial role in the outcome of this infection, the responsibility of hypogammaglobulinemia (HGG) as a predisposing condition for CDAD has not been studied in SOT. We analyzed the incidence, clinical presentation, outcome and risk factors, including HGG, of CDAD after HT. METHODS: Two hundred thirty-five patients who underwent HT (1993 to 2005) were included. Transplantation procedure and immunosuppression were standard. From January 1999 HGG was systematically searched and corrected when IgG levels were <400 mg/dl or severe infection was present. Toxin-producing C. difficile was detected by means of cytotoxin assay and culture of stool samples. Patients with and without CDAD were compared for identification of risk factors. RESULTS: CDAD was detected in 35 patients (14.9%). Incidence decreased significantly since HGG was sought and treated: 29 (20.6%) in the first period, and 6 (6.4%) in the second (p = 0.003). CDAD appeared a mean of 32 days (range 5 to 3,300 days) after HT. No related death or episode of fulminant colitis was detected. At least one episode of recurrence was noted in 28.6% of patients. Severe HGG was found to be the only independent risk factor for CDAD after HT (RR 5.8; 95% CI: 1.05 to 32.1; p = 0.04). CONCLUSIONS: C. difficile is a significant cause of diarrhea in HT recipients and post transplant HGG is independently associated with an increased risk. The potential role of immunoglobulin administration in this population requires further study. PMID- 17845930 TI - Cardiac reserve in the transplanted heart: effect of a graft polymorphism in the beta1-adrenoceptor. AB - BACKGROUND: Polymorphism of the beta1-adrenoceptor (beta1-AR) affects outcome and beta-blocker efficacy in patients with heart failure. We studied the influence of the beta1-AR Ser49Gly polymorphism on cardiac reserve in transplanted hearts. METHODS: Beta1-AR polymorphism was determined by allelic discrimination analysis. Patients were divided into two groups: either homozygous for Ser49 (n = 15) or with Gly49 in one or both alleles (Gly49; n = 5). Patients underwent a maximal bicycle exercise test and echocardiographic evaluation at rest and during low dose dobutamine stress. RESULTS: Patients with Gly49 grafts had better physical endurance (144 +/- 26 vs 112 +/- 31 W, p = 0.03), a trend toward better chronotropic reserve (deltaHR 64 +/- 13 vs 47 +/- 16 bpm, p = 0.056) during exercise, and lower resting heart rate (82 +/- 7 vs 90 +/- 7 bpm, p = 0.04) than those homozygous for Ser49. There were no significant differences in left ventricular ejection fraction (LVEF), with the exception of a decrease in cardiac reserve in patients with the Gly49 variants at the lowest dose of dobutamine (deltaLVEF -4.4 +/- 1.5 vs 2.2 +/- 5.8%, p = 0.04). Doppler myocardial tissue velocities of early relaxation were increased in patients with the Gly49 variants compared with patients homozygous for Ser49, both at rest (14.5 +/- 3.2 vs 10.4 +/- 2.0 cm/s, p = 0.03) and during the lowest dose of dobutamine (15.0 +/- 3.7 vs 10.9 +/- 2.5 cm/s, p = 0.04). CONCLUSIONS: Heart transplant patients with the beta1-AR Gly49 variants had a lower heart rate, and better stress endurance and diastolic function compared with patients homozygous for Ser49. They also showed a trend toward better chronotropic reserve. These results provide a possible explanation for differences in cardiac reserve among patients with heart transplants. PMID- 17845931 TI - Response of the oxygen uptake efficiency slope to orthotopic heart transplantation: lack of correlation with changes in central hemodynamic parameters and resting lung function. AB - BACKGROUND: Recently, a new linear measure of ventilatory response to exercise, the oxygen uptake efficiency slope (OUES), was proposed in the evaluation of heart failure patients. No data are available on the response of the OUES after orthotopic heart transplantation (HTx). METHODS: Thirty patients who underwent HTx between 1999 and 2003 were included in the study. Data from maximal cardiopulmonary exercise test, resting pulmonary function and hemodynamic assessment were collected before the transplant at time of screening and 1 year after HTx. RESULTS: During the first year after HTx, OUES and normalized OUES for body weight (OUES/kg) increased significantly from 15.6 +/- 4.9 to 19.7 +/- 4.8 (p < 0.05). Changes in OUES/kg were significantly correlated with changes in peak VO2, VAT and peak VE, and inversely to changes in peak VD/VT, but not to changes in VE/VCO2 slope (all p < 0.05). Changes in OUES or OUES/kg did not correlate with any changes in measures of resting lung volumes or capacities and measures of central hemodynamic function after HTx. CONCLUSIONS: OUES improved significantly after HTx, but, similar to other exercise parameters, remained considerably impaired. The changes in OUES were highly correlated with the improvements in other exercise variables, but did not correlate with marked improvements in central hemodynamics or resting lung function. PMID- 17845932 TI - Assessment of pulmonary vascular resistance by Doppler echocardiography in patients with pulmonary arterial hypertension. AB - BACKGROUND: Assessment of pulmonary artery pressures, cardiac output (CO) and pulmonary vascular resistance (PVR) is crucial in the management of patients with pulmonary arterial hypertension (PAH). The aim of the present study was to investigate whether Doppler echocardiography can be used to determine PVR in patients with PAH. METHODS: Forty-two patients were included and Doppler echocardiography was performed simultaneously (n = 22) and non-simultaneously (n = 60) with right heart catheterization. The tricuspid regurgitation velocity was used to estimate pulmonary arterial peak systolic and diastolic (PADP) pressures (Bernoulli equation). At the time of pulmonary valve opening, right ventricular pressure equals PADP. The tricuspid regurgitation velocity at the time of pulmonary valve opening was measured by superimposing the time from the QRS to the onset of pulmonary flow on the tricuspid regurgitation velocity envelope. Pulmonary capillary wedge pressure, right atrial pressure and CO were assessed using standard Doppler echocardiography methods. Right heart catheterization was performed using Swan-Ganz catheters and thermodilution for CO determination. RESULTS: The differences (mean +/- SD) between catheter and simultaneous/non simultaneous Doppler echocardiography were 0.3 +/- 0.8 (p = 0.10)/-0.3 +/- 1.1 (p = 0.06) liter/min for CO, 2.9 +/- 5.1 (p = 0.02)/-1.2 +/- 7.4 (p = 0.2) mm Hg for the transpulmonary gradient (TPG) and 0.3 +/- 2.1 (p = 0.65)/0.8 +/- 2.4 (p = 0.02) Wood unit for PVR. The correlation coefficients between catheter and simultaneous/non-simultaneous Doppler echocardiography were 0.86/0.75 for CO, 0.92/0.90 for TPG and 0.93/0.92 for PVR. CONCLUSIONS: A comprehensive hemodynamic assessment that includes CO, TPG and PVR can be provided by Doppler echocardiography in patients with severe pulmonary hypertension. PMID- 17845933 TI - Hepatocyte growth factor prevents pulmonary ischemia-reperfusion injury in mice. AB - BACKGROUND: Ischemia-reperfusion (IR) injury after lung transplantation leads to significant morbidity and mortality in recipients, which remains the major obstacle in clinical lung transplantation. To reduce pulmonary graft dysfunction and improve prognosis after lung transplantation, prevention of IR-induced lung injury in the peri-operative period is required. In the present study, we investigated the effects of recombinant hepatocyte growth factor (HGF) on pulmonary IR injury using a murine model system. METHODS: To assess the protective effect of HGF against lung injury, mice with pulmonary IR were divided into two groups and injected with 500 microg/kg of human recombinant HGF or the same dose of saline alone as a control. RESULTS: After pulmonary IR injury, the lung injury score increased in a time-dependent manner up to 24 hours. A significant reduction of lung injury score was observed with the administration of exogenous HGF. Moreover, the ratio of apoptotic cells was significantly reduced in mice treated with HGF. Significantly increased expression of Bcl-xL was observed after IR in mice administered HGF as compared with saline-treated controls. In contrast, expression of Bax was reduced significantly in HGF-treated mice. Serum levels of endogenous murine HGF were increased significantly in HGF treated mice. CONCLUSIONS: Our findings indicate that administration of exogenous HGF ameliorates the pulmonary tissue injury induced by IR, which may provide an alternative for prevention of IR-induced lung injury in the peri-operative period in lung transplantation. PMID- 17845934 TI - Epstein-Barr virus-associated multifocal leiomyosarcomas arising in a cardiac transplant recipient: autopsy case report and review of the literature. AB - Epstein-Barr virus (EBV) associated smooth muscle tumors (SMTs) have been described in patients with acquired immune deficiency syndrome (AIDS) and, more recently, in association with immunosuppression after solid-organ transplantation. We present the autopsy findings of multiple leiomyosarcomas (LMSs) in a 24-year old man who died 18 months after undergoing orthotopic cardiac transplantation for idiopathic cardiomyopathy. The recognition of EBV driven LMS developing in cardiac transplant recipients in multiple unusual sites is crucial for the management of these patients and should include complete surgical removal anti-viral therapy and modulation of immunosuppression. PMID- 17845935 TI - Chylothoraces after lung transplantation for lymphangioleiomyomatosis: review of the literature and utilization of a pleurovenous shunt. AB - Chylous effusions are a well-described complication of lymphangioleiomyomatosis (LAM) in both pre- and post-transplant patients. Chylous effusions can cause significant morbidity among patients and most treatment modalities have limitations to complete success. We describe the use of a pleurovenous shunt to treat a refractory chylous effusion in a patient after lung transplant for LAM. After shunt placement, the patient had complete resolution of the chylous effusion and subsequent discharge home after a prolonged hospitalization. The use of a pleurovenous shunt for refractory chylous effusions is a viable option after conventional therapy fails. PMID- 17845936 TI - Drive-line exit-site infection in a patient with axial-flow pump support: successful management using vacuum-assisted therapy. AB - Infection remains one of the most common causes of mortality during left ventricular assist device (LVAD) support, and poses major challenges to surgeons implanting these devices. We describe the case of a patient supported with an axial-flow pump for dilative cardiomyopathy, who experienced drive-line exit-site infection and was treated with extensive surgical debridement and reconstruction by applying vacuum-assisted therapy. He remained infection-free after wound healing and, after 7 months of mechanical support, had native heart function recovery and underwent LVAD removal. PMID- 17845937 TI - Coronary plaque classification using intravascular ultrasound-radiofrequency analysis in a heart transplant patient with severe atherosclerosis. PMID- 17845938 TI - Patent foramen ovale management before and after heart transplantation: a simple algorithm. PMID- 17845939 TI - Anaphylaxis from aprotinin re-exposure during heart transplantation. PMID- 17845940 TI - Resolution of protein-losing enteropathy after successful heart transplantation in an adult patient with arrhythmogenic right ventricular cardiomyopathy (ARVC). PMID- 17845941 TI - The challenge of homograft tissue banks: the viability of cryopreserved valvular homografts. PMID- 17845942 TI - Nursing home safety matters, but it's not an easy matter. PMID- 17845943 TI - How should nursing homes use vaccine to prevent zoster? PMID- 17845944 TI - Intensive session: New approaches to medical issues in long-term care. AB - This article, based on a series of presentations at the American Medical Directors Association, briefly highlights new advances in medical areas of interest to long-term care physicians. The areas discussed are heart failure, vitamin D, falls, new treatments for diabetes mellitus, blood pressure measurement, anemia, clinical nutrition, pressure ulcers, Clostridium difficile, insomnia, and antipsychotic therapy. PMID- 17845945 TI - Update on osteoporosis management in long-term care: focus on bisphosphonates. AB - Osteoporotic fractures are potentially devastating and associated with high morbidity and substantial economic burden. Residents of long-term care facilities are at greater risk of osteoporosis and its related fractures than those living in the community, yet osteoporosis is underdiagnosed and undertreated in these settings. Bisphosphonates are approved by the Food and Drug Administration for the treatment and prevention of osteoporosis in postmenopausal women. As a class, bisphosphonates have been shown to increase bone mineral density, decrease the markers of bone resorption, and reduce the risk of osteoporotic fractures. The 3 approved bisphosphonates are alendronate, risedronate, and ibandronate. Alendronate and risedronate are dosed daily or weekly and ibandronate, the most recently approved bisphosphonate, has been approved for monthly oral dosing or as an intravenous formulation to be given intermittently (every 3 months). In addition, other products with different mechanisms of action are in the pharmaceutical pipeline and may offer additional management options. PMID- 17845946 TI - Nurses' and nursing assistants' recognition of depression in elderly who depend on long-term care. AB - INTRODUCTION AND METHOD: Recognition and treatment of depression is a quality indicator for nursing homes. Nurses and nursing assistants are in a particularly good position to recognize depression in long-term care. How well do nurses and nursing assistants recognize depression, compared with a DSM-IV diagnosis of depression? To answer this question a critical review of relevant literature in PubMed searches was performed. RESULTS: It was found that nurses and nursing assistants recognize true depression in about 55% (sensitivity 42% to 78%) and "over-recognized" depression in about 40% of nondepressed patients (specificity 56% to 67%). DISCUSSION: The prominent role of nurses and nursing assistants in daily mental health care is not reflected in the number of methodologically sound studies. Sensitivity of the Geriatric Depression Scale (GDS) is about 50% higher than nurses' recognition of depression. A specific recommendation for specially trained nursing assistants in depression management and standard use of screening scales in an update of the American Medical Directors Association's Clinical Practice Guideline on Depression might improve depression recognition, as well as nursing assistants' work satisfaction and staff turnover. CONCLUSION: Recognition of depression by nurses and nursing assistants is low. Standard use of a screening scale like the GDS would improve recognition of depression in the elderly. More research is needed aimed at how nursing assistants can empower their role as mental health care provider in long-term care. PMID- 17845947 TI - A comparison of two distribution methods on response rates to a patient safety questionnaire in nursing homes. AB - BACKGROUND: Survey research focusing on patient safety issues in the nursing home sector poses challenges owing to nursing staff turnover rates, and the adversarial and punitive nature of US nursing home regulation which may promote a negative culture of distrust. Using a patient safety questionnaire, we compared two methods of survey distribution on response rates, respondent sample characteristics, and resident safety ratings. We hypothesized that employees may provide overly positive perceptions when the surveys are distributed on-site as opposed to distribution to employees' homes, as has been reported by studies evaluating patient satisfaction in other settings. METHODS: In August 2003, 26 nursing homes indicated their distribution method preference (mail directly to staff members' homes vs. distributed at work) for a survey determining perceptions of resident safety. Facilities provided lists of currently employed nurses (n=721) and nursing assistants (n=1,233). The survey process included an initial mailing of the survey packet, a reminder postcard, a re-mail of the survey packet to non-respondents to the initial survey, and a final reminder postcard. Return envelopes were addressed to the research team. RESULTS: In nursing facilities where surveys were distributed at work, a greater proportion of respondents were identified as no longer currently employed. Response rates were similar regardless of distribution method, but with greater variability in the facility-specific response rate in surveys distributed at work. Regardless of staffing type, yield of the first mailing was lower and yield of the second mailing higher in homes with surveys distributed at work than those mailed directly to respondents' homes. While characteristics of nurses were similar regardless of wave, nursing assistant responders to second mailing were more likely to be black relative to responders to the first wave. CONCLUSION: Distributing surveys at the workplace may not result in a reduction of response rate, but may provide overly positive perceptions of patient safety issues. Mailing directly to homes may result in less facility-level variability in response rates. Multiple mailings may increase the diversity of the respondent pool. PMID- 17845949 TI - Association between inflammation-associated cytokines, serum albumins, and mortality in the elderly. AB - OBJECTIVE: To investigate the association between serum albumin, prealbumin, various serum inflammation associated-cytokines, and mortality in older geriatric recuperative care patients. DESIGN: A prospective cohort study. SETTING: A geriatric rehabilitation unit of a university-affiliated Department of Veterans Affairs hospital. PARTICIPANTS: Participants were 53 geriatric patients (mean age 78 +/- 7.3, 96% male) admitted to a Geriatric Evaluation and Management (GEM) unit. Patients with documented near-terminal medical disorder, overt infections, and any systemic or localized inflammatory disorders were excluded. MEASUREMENTS: Inflammation-associated cytokines (IL-8, IL-1beta, IL-6, IL-10, TNF-alpha), albumin, prealbumin, and C-reactive protein were measured at hospital discharge and each subject was then tracked for 1 year. MAIN RESULTS: By Cox Proportional Hazards Regression analysis, the strongest predictor of mortality within 6 months of study entry was the serum IL-6. For each log increase in IL-6, there was nearly a 9-fold greater 6-month mortality risk (RR 8.99, 95% CI 1.65 to 49.03). The association between albumin and mortality was no longer significant after controlling for IL-6. There was a strong inverse correlation between IL-6 and both albumin (R2 0.39, P < .001) and prealbumin (R2 0.41, P < .001). CONCLUSION: Subclinical inflammation appears to be an important factor contributing to low serum albumins in older recuperative care patients and may confound the association between albumin and mortality in this population. More in-depth studies of these associations are warranted. PMID- 17845948 TI - Use of osteoporosis medications in older nursing facility residents. AB - INTRODUCTION: Epidemiologic studies demonstrated that 70% to 85% of nursing home residents have osteoporosis. Few studies report comprehensive information about treatment of osteoporosis in nursing facilities. OBJECTIVE: To determine the prevalence of osteoporosis treatment and identify resident characteristics associated with the use of antiresorptive medications or supplements indicated to treat osteoporosis in nursing homes. METHODS: The study design was cross sectional. The Systematic Assessment of Geriatric Drug Use via Epidemiology database provided the data. From this database, 186,221 residents were identified as newly admitted to nursing facilities in Kansas, Maine, Missouri, Ohio, and South Dakota between 1998 and 2000. The outcome measure was the use of antiresorptive medications (alendronate, risedronate, calcitonin, estrogen, raloxifene) or supplements (calcium with vitamin D) indicated for treatment of osteoporosis. The independent variables included demographic, health status, and fracture risk factors. RESULTS: Of the overall sample, 9.1% received antiresorptive medications and/or supplements indicated for osteoporosis treatment. The most commonly used treatment was the combination of calcium and vitamin D (5.0%). Calcitonin (2.5%) use exceeded that of any other antiresorptive. Multivariable logistic regression analyses revealed that a diagnosis of osteoporosis and female gender were strongly associated with being more likely to receive an osteoporosis treatment (OR 6.34 with 95% CI 6.11-6.64 and OR 2.67 with 95% CI 2.53-2.83 respectively). The number of medications residents received was also strongly associated with receiving osteoporosis treatment. Being black and having 4 or more active diagnoses were strongly associated with lower odds of receiving treatment (OR 0.63 with 95% CI 0.57-0.68 and OR 0.71 with 95% CI 0.68-0.74 for 4 to 6 diagnoses). DISCUSSION: Newly admitted nursing facility residents infrequently received an indicated osteoporosis treatment, including calcium with vitamin D, despite the expected high prevalence of osteoporosis in this setting. Few demographic, health status, and fracture risk factors were strongly associated with receiving indicated treatment. PMID- 17845950 TI - Prediction of 6-month mortality in nursing home residents with advanced dementia: validity of a risk score. AB - OBJECTIVE: Prognostic information is important for guiding palliative care planning for patients with dementia. We aim to validate a risk score that uses Minimum Data Set (MDS) to estimate 6-month mortality for nursing home residents with advanced dementia. DESIGN: Two cohort studies. SETTING: Six nursing homes in The Netherlands, and 35 nursing homes in Missouri. PARTICIPANTS: Long-term stay residents with advanced dementia: 288 Dutch residents and 269 residents from Missouri who also had a lower respiratory tract infection (LRI). MEASUREMENTS: Patient risk factors and 6-month mortality. RESULTS: Six-month mortality rates were 24.3% for Dutch residents, and 36.8% for US residents. The risk score's AUROC was 0.65 (CI 0.58-0.72), and 0.64 (CI 0.58-0.71), respectively. For the large majority of residents, observed mortality in the 2 validation cohorts were comparable to the development cohort. Among the few residents identified as at very high risk according to the risk score, observed mortality was lower than expected. CONCLUSION: The original mortality risk score predicted 6-month mortality with reasonable accuracy in 2 validation cohorts of nursing home residents with advanced dementia. Thus, the performance of the risk score, at least over the range of low to moderate risk (up to around 40% risk of mortality), can be generalized to long-stay (versus recently admitted) residents with advanced dementia, and to those with LRI. PMID- 17845951 TI - Do objective measurements of physical function in ambulatory nursing home women improve assessment of functional status? AB - OBJECTIVE: To compare the functional status of ambulatory women in four academic nursing homes using standardized rating scales and physical performance measures used in community settings. DESIGN: Observational cohort. PARTICIPANTS: Women older than 65 years, ambulatory with or without an assistive device. INTERVENTIONS: Direct comparison of the Functional Independence Measure and the Performance Self Maintenance Score with objective measure of the Get-up-and-go test, a six minute walk, and a six meter walk. RESULTS: Two variables, the gait speed and creatinine clearance, correctly classified 80% of subjects with higher functional status defined by subjective rating scales. CONCLUSION: Although gait speed calculated by a six meter walk is easily performed and highly correlated with subjectively assessed functional status, the majority of these ambulatory women nursing home residents exceeded the population means for each of the performance-based physical function measures. PMID- 17845952 TI - Evidence-based clinical pathways to manage urinary tract infections in long-term care facilities: a qualitative case study describing administrator and nursing staff views. AB - OBJECTIVES: This article examines the views of nursing staff and administrators in long-term care facilities (LTCFs) regarding a clinical pathway for managing urinary tract infections (UTIs) in LTCF residents. DESIGN: A qualitative (case study) design was used. SETTING: Data were collected from 8 LTCFs in southern Ontario and 2 in Iowa enrolled in a larger randomized controlled trial of clinical pathway for managing UTIs in LTCF residents, conducted between September 2001 and March 2003. The clinical pathway, designed to more effectively identify, diagnose, and treat UTIs, and reduce inappropriate antibiotics use for asymptomatic UTIs, introduced 2 decision tools to determine when to order a urine culture and initiate antibiotic treatment for suspected UTIs. PARTICIPANTS: We conducted 19 individual interviews with administrators and 10 focus groups with 52 nurses. FINDINGS: Nurses generally thought that the pathways were well developed and easy to use, and administrators believed they were an important educational resource. Barriers to their use varied by group-initial lack of buy in from nurses (medical directors), additional work (directors of nursing), and the need to change the protocol to exclude certain residents based on prior health conditions and/or pressure from physicians or families (nurses). CONCLUSIONS: Both administrators and staff, once familiar with a new clinical protocol to improve UTI management in LTCFs, generally supported its use. PMID- 17845954 TI - Biostatistics note: Potential use of receiver operating characteristics curve in assessing accuracy of measuring urine thread protein. PMID- 17845955 TI - Re: To evacuate or not to evacuate: lessons learned from Louisiana nursing home administrators following Hurricanes Katrina and Rita. PMID- 17845957 TI - The difference is in the details. PMID- 17845958 TI - It's all over but the shouting. PMID- 17845959 TI - Diagnostic imaging centers for hospitals: a different business proposition for outpatient radiology. PMID- 17845960 TI - Teaching physician compliance. PMID- 17845961 TI - ACR Appropriateness Criteria on staging and follow-up of ovarian cancer. AB - Ovarian cancer is the most common cause of cancer death from gynecologic malignancy in women. The diagnosis and treatment of ovarian cancer are especially challenging because of the high prevalence of benign disease in the ovaries and the tendency for late presentation of ovarian cancer after it has spread. The role of diagnostic imaging is in lesion detection, lesion characterization, preoperative staging, and the prediction of disease resectability that may require chemotherapy and later debulking for improved survival. PMID- 17845962 TI - Should 12 months of training be required before diagnostic radiology residents take independent call? A survey of the Association of Program Directors in Radiology. AB - To assess program director's reactions to a Residency Review Committee rule change requiring diagnostic radiology residents to complete 12 months of training prior to taking independent call, 303 Association of Program Directors members were surveyed. A total of 147 members responded (48.5% response rate). Overall, 66.1% of respondents were opposed to the change, 21.1% were in favor of it, and 12.8% were neutral. Although this rule change has already been accepted by the residency review committee for implementation July 1, 2008, there has been much debate over this modification and the impact it will have on varying programs. PMID- 17845963 TI - Proposed ACGME change in length of radiology residency training before independent call: results of a survey of program directors and chief residents. AB - PURPOSE: To assess radiology residency program directors' and chief residents' views regarding the Radiology Residency Review Committee's proposed revision of program requirements which would delay independent call until a resident has had 12 months of radiology training. METHODS: A Web-based survey was distributed electronically to the program directors and chief residents of 188 radiology residency programs. Survey responses were collected for two weeks in November December 2006. RESULTS: The survey was completed by 91 Program Directors and 165 Chief Residents. There were no statistically significant differences between the two groups of respondents on any of the 9 questions pertaining to the proposed call requirement change. Approximately 70% of the program directors and 80% of the chief residents disagreed or disagreed strongly that they were in favor of the proposed ACGME change. Strong opposition to the change was independent of both program size and current compliance with the proposed change. Over 70% in both groups disagree or strongly disagree that the proposed change would positively affect residency training. CONCLUSIONS: The majority of survey respondents oppose changing the minimum required length of radiology residency training prior to residents' providing independent on-call radiology interpretations from 6 months to 12 months. PMID- 17845964 TI - Special section--First year residents taking call: changing radiology resident call. PMID- 17845965 TI - Total-body screening: preliminary results of a pilot randomized controlled trial. AB - PURPOSE: The authors performed a pilot randomized controlled trial of total-body screening to assess the feasibility of a full-scale study. MATERIALS AND METHODS: After informed consent, 50 asymptomatic people were randomized to either the intervention arm (total-body screening with multidetector computed tomography) or the control arm (no screening for 3 years). The study was approved by our institutional review board and was compliant with the Health Insurance Portability and Accountability Act. Images were interpreted independently by 6 radiologists from 2 institutions. Subjects in both study arms completed periodic health questionnaires and medical utilization forms over 2 years. Key outcome variables were the incidence of symptomatic disease, medical costs, and patient reported health. RESULTS: Sixteen screened subjects (64%) had abnormal findings on screening. A second interpretation of the images yielded a similar overall rate but with considerable variability at the subject level. No cancers were detected. Ninety percent of subjects were compliant at 2 years. Medical costs were twice as high for screened subjects, with considerable between-subject variability. Screened subjects reported fewer physical limitations than unscreened subjects. CONCLUSION: A full-scale randomized controlled trial of total-body screening will need to account for the large interreader variability in interpreting the images, the high rate of incidental findings, and the low prevalence of cancers. A full-scale study using mortality as the endpoint does not seem feasible at this time. PMID- 17845966 TI - The expert witness: understanding the rationale. AB - The origins of the use of expert witnesses to assist courts in helping understand the required conduct in determining the standard of care provides a basis for recognizing the consultant role sought in judicial proceedings. Both rules of evidence and court decisions have evolved in a manner that encourages the introduction of expert testimony while conditioning its use to avoid unfair bias. Trial court judges decide on permitting such testimony, while legal counsel is responsible for helping juries determine its importance and reliability. Certain types of restrictions and adverse consequences for misstatements exist but are subordinated to the trial process in most circumstances, a process that varies among different jurisdictions. PMID- 17845967 TI - Accuracy of information on imaging requisitions: does it matter? AB - Imaging requisitions are the major manner in which clinicians communicate to radiologists with regard to imaging studies they are requesting. Errors in the information provided on requisitions may have a deleterious effect on the quality of the imaging reports and services provided by radiologists. The author reviews all of the many problems and errors that can occur on imaging requisitions in addition to inadequate clinical histories. The author then discusses how to identify and resolve these errors. PMID- 17845968 TI - Turf wars in radiology: what must academic radiology do? AB - In a previous article in this series, the authors called on private practice radiology groups to better support radiology research financially but also pointed out that academic radiology must make some changes as well. In this article, the authors discuss those changes in detail. They include revising the structure of the radiology residency, changing the timing of the American Board of Radiology oral examinations, requiring that all residents receive research training, and emphasizing the value of clinical and translational research. The Society of Chairmen of Academic Radiology Departments needs to assume a leadership role in implementing these changes. PMID- 17845969 TI - The evolving role of radiologists within the health care system. AB - The traditional view of radiologists as physicians who add value to the health care system solely by generating and interpreting diagnostic images is outdated. Radiologists' roles have expanded to encompass economic gatekeeping, political advocacy, public health delivery, patient safety, quality-of-care improvement, and information technology. It is through these roles that radiologists will continue to find new ways to add value to the health care system. PMID- 17845970 TI - Musculoskeletal radiology curriculum for radiology residents. AB - This article outlines a curriculum for resident education in musculoskeletal radiology that addresses the current requirements for assessment of the general competencies as set forth by the Accreditation Council for Graduate Medical Education. PMID- 17845971 TI - Life's stages. PMID- 17845972 TI - Service delivery and service quality in radiology. PMID- 17845973 TI - DICOM and radiology: past, present, and future. PMID- 17845974 TI - Ben Felson. PMID- 17845975 TI - [Gemcitabine and pemetrexed update]. PMID- 17845976 TI - [Gemcitabine: from preclinic to clinic passing by pharmacokinetics]. AB - Gemcitabine or Gemzar forms part of the class of the anti-cancer drugs antimetabolites. Gemcitabine is a structural analogue of the deoxycytidine with 2 fluorine atoms. There is a strong analogy between gemcitabine and cytosine arabinoside (Aracytine or Depocyt), at the same time structural, mechanistic and metabolic. However, if the intracellular derivatives triphosphate of gemcitabine seem more stable than those of the cytarabine, the two molecules move away from share their therapeutic activity. Indeed, if the cytosine arabinoside finds its place in the treatment of hematologic diseases, myeloblastic or lymphoblastic acute leukaemia and in acute myeloid leukaemias and myelodysplasy, gemcitabine sees its indications in the treatment of solid tumours such as non small cell lung cancer, adenocarcinoma of the pancreas, cancer of the bladder and metastatic breast cancer. PMID- 17845977 TI - [Updates on gemcitabine on metastatic breast cancer]. AB - Gemcitabine is one of the key products actually used in metastatic breast cancer. Thanks to its favourable toxicity profile, gemcitabine can be used in combination with a number of drugs. Recently published and presented results from different trials may modify our perception and strategies regarding metastatic breast cancer. In this overview we will focus on the results of these trials and particularly those recent concerning the combination of gemcitabine with taxanes, vinorelbine, platinum salts and trastuzumab. PMID- 17845978 TI - [Gemcitabine and non small-cell lung cancer]. AB - Questions raised during gemcitabine development reflect non small-cell lung cancer (NSCLC) history during last 10 years. Third generation therapies (gemcitabine, vinorelbine and taxanes) combined with platinium compounds are now to be prescribed in almost all clinical situations, from surgically removed tumors to metastatic diseases. The 30% response rate usually reported in advanced disease (with a median survival of 10 months) has to be improved and a more global approach is nowadays mandatory, including targeted agents. This review sum up the clinical situations in which gemcitabine can be prescribed (advanced disease), or shall be prescribed (adjuvant setting, combination with anti angiogenic agent or EGFR inhibitors), and highlight opening questions. PMID- 17845979 TI - [Gemcitabine and digestive carcinomas]. AB - Gemcitabine is a well-tolerated anti-tumour drug with broad-spectrum activity. It is now recommended for treatment in an increasing number of tumours. Locally advanced or metastatic pancreatic cancer is the only digestive cancer for which it has yet been approved. Numerous phase III trials have addressed gemcitabine's dosage, infusion modalities, and its potential association with other anti-tumour drugs in pancreatic cancer. Standard recommended treatment for this disease in 2006 is gemcitabine monotherapy following Burris'protocol, that is 1000 mg per square meter in a 30 minute-infusion weekly for seven weeks, one week off and then weekly for three weeks, repeated every 4 weeks. Many phase I or II trials have been carried out in all other digestive cancers. They show gemcitabine's potential activity, especially in esophageal cancer, biliary tract adenocarcinoma and hepatocellular carcinoma. Nevertheless, larger studies are required to confirm this efficacy. The aim of this review is to describe the trials that have contributed to determine gemcitabine's infusion modalities in pancreatic cancer. We will then present the studies that have been carried out in other digestive cancers. PMID- 17845980 TI - [Gemcitabine and pemetrexed in genito-urinary tumors treatment]. AB - Among genito-urinary tumors, gemcitabine is indicated only for the treatment of locally advanced and metastatic urothelial cancer. The combination of gemcitabine and cisplatin is a new standard in this disease. Gemcitabine shows activity in refractory germ cell tumors. In salvage treatment its role is ongoing evaluation. The combination of gemcitabine and 5-fuoruracile has modest activity in renal cell carcinoma. Pemetrexed is not indicating in genitor-urinary tumors, further evaluation in urothelial cancer is warranted. PMID- 17845981 TI - [Docetaxel and gemcitabine combination in soft-tissue sarcomas treatment]. AB - Soft-tissue sarcomas (STS) are usually sensitive to doxorubicine and/or ifosfamide. When tumors become refractory to these two drugs, chemotherapeutic options are limited. All the drugs tested generally yield occasional or negligible response, with response rates lower than 20% and a poor duration of response. No second-line chemotherapy have been clearly adopted. In vitro synergistic cytotoxicity has been reported with gemcitabine and docetaxel combination. Promising anti-tumor activity has been described with gemcitabine alone, docetaxel alone or these two drugs in combination These treatments were generally well tolerated. The best response have been observed in leiomyosarcomas. According to these results, gemcitabine and docetaxel combination might be of interest in STS. However, a phase III study is required to better evaluate the real advantage of this treatment. PMID- 17845982 TI - [Gemcitabine and radiotherapy in non-small cell lung cancer: dolce vita at last!]. AB - A hallmark of locally advanced non-small cell lung cancer is its high local and systemic recurrence rates, ranging from 60% to 80%. Radiotherapy has shown its efficacy in controlling the tumor and in increasing overall survival, especially with combined sequential or concurrent chemotherapy to allow an anti-tumoral synergy. Gemcitabine, a new generation cytotoxic agent, is a potent radiosensitizer in vitro, and thus appears as a promising molecule in these multimodal therapeutic regimens. If the initial trial with gemcitabine and radiation produced unacceptable toxicities, lessons were learned from this study, and further phase I-II trials demonstrated that in a clinical trial setting, gemcitabine and radiation can be given safely, both in sequential and concurrent chemoradiation regimens, leading to high response rates and prolonged survival. Gemcitabine-radiation combination is currently integrated in phase III trials evaluating the optimal therapeutic sequence in locally advanced non-small cell lung cancer, and appears as one of the most promising therapeutic regimen in thoracic oncology. PMID- 17845983 TI - [Pemetrexed: from preclinic to clinic]. AB - The pemetrexed (Alimta) is a new generation antifolate prescribed in the treatment of mesothelioma in association with cisplatin and in the 2nd line treatment of locally advanced or metastatic non-small lung cancer. Pemetrexed is an original molecule, different from the other antifolates. On the opposite methotrexate, pemetrexed inhibits several enzymes involved in the synthesis of purines and pyrimidines, in particular thymidylate synthase, dihydrofolate reductase, glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4 carboxamide ribonucleotide formyltransferase. Pemetrexed is transported in cells by three receptors, which make easier its cellular penetration. On the other hand, the polyglutamation of the product by the folylpolyglutamate synthetase increases considerably its activity notably towards the thymidylate synthase. Finally, unlike methotrexate, pemetrexed presents an atypical effect on cellular synchronisation. The wide spectre of activity of pemetrexed confers it a therapeutic advantage with regard to the other antifolates specific of one or other one enzymes. The clinical results show an anti-tumoral activity against non small lung cancer and in mesothelioma and recently towards other solid tumours, in particular in head an neck, colon and mammary cancers. PMID- 17845984 TI - [Update of pemetrexed in thoracic oncology]. AB - Efficacy of pemetrexed has been demonstrated in malignant pleural mesothelioma. This is based on the result of a phase III trial comparing cisplatin and pemetrexed to cisplatin alone, with a significant improvement of median survival in the doublet arm (11.4 versus 8.8 months, p = 0.048). This combination represents a new standard of chemotherapy in this disease. In non small cell lung cancer, pemetrexed has been compared as second line chemotherapy to docetaxel : efficacy was comparable (median survival of 8.3 months with pemetrexed and 7.9 months with docetaxel) but significant less hematological toxicity was observed in the pemetrexed arm compared to the docetaxel arm, especially grade 3-4 neutropenia (respectively 5.3 and 40.2%) and febrile neutropenia (1.9 versus 12.7%). The place of pemetrexed in elderly patients is under evaluation. PMID- 17845985 TI - [Pemetrexed development in oncology]. AB - The pemetrexed disodium (Alimta), LY231514) is the first antifolate able to inhibit at the same time the synthesis of purins and pyrimidins. Many therapeutic tests were carried out in clinical situations where the methotrexate and the fluorouracil had been the proof of their effectiveness. It then showed an interesting activity in a great number of tumours but with very different profiles of tolerance according to the studies and pathologies. The explanation will come in 2001 by the description from the relation between the vitamin deficiencies among treated patients and occurred from toxicities. The two randomized studies carried out in the malignant pleural mesothelioma and the non small cell lung cancer made it possible to establish its utility and to record the pemetrexed in these clinical situations. Others axes of development remain possible, but the results are stanby or to confirm as in squamous-cell cancer in the head and neck and breast, digestive or urinary tracts cancer. In all the cases, the optimization of the pemetrexed in terms of amount/methods of administration and associations possible because of its profile of tolerance makes of it a molecule of chemotherapy with a future. PMID- 17845986 TI - [Gemcitabine and pemetrexed: novel associations and mechanisms of resistance]. AB - Gemcitabine and pemetrexed are two novel antimetabolites with broad spectrum of antitumor activity and a safe toxicity profile. In addition, recent advances in cellular and molecular biology led to a better understanding of their mechanisms of action and resistance. Based on these latter advantages, several studies have been conducted using pemetrexed or gemcitabine either alone or with novel targeted therapies. Taken together, these recent data should result in a better and more specific use of these two very promising drugs. PMID- 17845987 TI - [Cancer of the prostate: recent findings and the immediate future]. PMID- 17845988 TI - [T1-T2 prostate cancer: treatment by radiation therapy]. AB - Prostate cancers are a complex entity. Many factors must be taken in account in the therapeutic discussion. Identification of group of risk authorizes to better adapt the treatment. External radiation therapy is efficient and the analysis of the literature shows that this technique is effective. With new modalities, in particular with conformal irradiation, it is possible to optimize the dose and to limit the risk of complications. Brachytherapy is an other possibility with very good result for patients of the low risk group. But these two modalities were never directly compared. This opportunity should be discuss in the future. PMID- 17845989 TI - [Adjuvant medical treatment or radiotherapy following radical prostatectomy or curative radiotherapy]. AB - Treatment of prostate cancer with a high risk of recurrence following local treatment (surgery or radiotherapy) remains a controversial subject. Adjuvant treatment must be scheduled if there are factors for a poor prognosis from the anatomopathologic results of biopsies or the excised prostate. The aim of this treatment is to destroy any remaining tumour cells after curative treatment. In a review of the literature, one can note the various adjuvant treatments according to their indications. A benefit has been demonstrated for adjuvant radiotherapy following radical prostatectomy with capsular invasion or positive margins. This is of interest in terms of survival with biological recurrence. However, no study has demonstrated a benefit in terms of overall survival. Following curative radiotherapy, there is also a specific benefit of adjuvant hormonal therapy. This benefit consists of a significant improvement in survival without progression, specific survival and overall survival. All in all, it would appear that patients with a high risk of progression who were initially treated by radiotherapy or radical prostatectomy can benefit from the adjuvant therapeutic alternatives that have demonstrated their interest. The decision to perform adjuvant treatment following curative treatment should be discussed at weekly interdisciplinary meetings. PMID- 17845990 TI - [Prostate cancer and chemotherapy]. AB - Androgen deprivation in patients with metastatic prostate cancer produces palliation of symptoms, PSA decrease and tumoral regression in most patients. After a brief period of disease regression lasting 18 to 24 months nearly all pts will progress to androgen independence disease (HRPC) with progressive clinical deterioration and ultimately death. Chemotherapy with mitoxantrone has been shown to palliate symptoms but did not extend survival. Two large randomized trials showed a survival benefit for pts with HRPC treated with docetaxel with a reduction risk of death by 21-24%, and significant improvement in palliation of symptoms and quality of life. New agents targeting angiogenesis, apoptosis, signal transduction pathway, used alone or in combination with docetaxel currently are under trial in an attempt to provide much needed improvements in outcome. Questions remains in suspend when and who need to be treated, earlier, in high risk as in adjuvant setting? Current data have demonstrated that neoadjuvant or adjuvant chemotherapy is relatively safe and feasible. Further investigation through prospective randomize trials is critical to define the precise role of this modality in high risk populations. PMID- 17845992 TI - [Prognostic factors of localised, locally advanced or metastatic prostate cancer]. AB - In prostate cancer, whatever the stage of the disease, the selection of a treatment strategy is based on prognostic factors. Clinical stage, serum PSA concentration and Gleason score are among the most recognised factors. A combination of these three parameters leads to a score used to define prognostic groups that are routinely used in daily practice. More recently, predictive statistical models have been developed that were associated with nomograms. The objective of nomograms is, for a given patient, to calculate his probability to develop disease extension or relapse based on clinical, biological, histological and therapeutic (radiotherapy, hormonotherapy) data. Such nomograms are not all validated and their application in daily practice is more difficult than that of classical prognostic classifications. Nowadays, the progress and accessibility to novel technologies applied to biology will make possible in the near future the assessment of new prognostic profiles based on genetic and/or proteomic tumour characteristics. PMID- 17845991 TI - [Interleukin-6 implication in prostate cancer]. AB - Interleukin-6 (IL-6) is secreted in great quantity in prostatic tumoral glandular tissue with a significant higher rate in hormono-refractory phase. Importance of IL-6 dependent mechanism in prostate cancer progression is well argued. IL-6 seems to be implicated in androgen receptor activation in lack of steroid ligand, apoptosis decrease and increase of invasive capacity and angiogenesis via three major signaling pathways: MAPK, STAT3 and PI3K-Akt. As AR is a key factor of prostate cancer progression, IL-6 implication in this activation underlines IL-6 importance in prostate cancer. IL-6 also induces neuroendocrine differentiation. This phenomenon received a detailed attention because it would take part in pathogenicity and progression of prostate cancer. Although complementary studies seem necessary, taking into account its strong implication in prostate cancer progression, IL-6 seems to be a new potential therapeutic target of prostate cancer. PMID- 17845993 TI - [Rare malignant tumours of the prostate]. AB - Among the rare malignant tumours of the prostate it is advisable to differentiate epithelial tumours with histologic variants of adenocarcinomas and non glandular carcinomas and mesenchymal tumours which represent less than 1% of these malignant tumours. PMID- 17845994 TI - [Locally advanced prostate cancer: definition, prognosis and treatment]. AB - According to d'Amico's criteria, high-risk localized prostate cancer are defined either by an extracapsular extension (T3 or T4), either by a high Gleason score (> 7) or a PSA rate higher than 20 ng/ml. Pelvic lymph node involvement also corresponds to locally advanced prostate cancer. Statistical models called nomograms have been developed to predict the probability of prostate cancer recurrence and are also used to define locally advanced patients. Prostate MRI may help to detect an extracapsular extension or a seminal vesicles involvement but remains still discussed. A bone scan, an abdominal and pelvic CT scan have to be performed in order to detect metastases. A pelvic lymph node dissection is recommended in order to adapt the treatment of these patients. Standard treatment for high-risk localized prostate cancer without lymph node involvement is now well defined. The association of both local radiation and a long androgen deprivation (GnHR agonist) showed an overall survival benefit (more than 10%). The radiation dose of 74 Gy is recommended. Other questions are still debating : the optimal duration of the hormonotherapy , the use of the bicalutamide 150 mg instead of GnRH agonists, the optimal radiation dose. Radical prostatectomy is no more considered as a standard treatment for these patients. Since the use of chemotherapy for metastatic patients showed a benefit in overall survival, the place of chemotherapy as adjuvant or neo-adjuvant treatment is questionned in several randomized phase III studies. Sometimes high-risk disease is diagnosed after performance of a radical prostatectomy. A postoperative radiation may be performed in order to decrease clinical and biochemical progression. The use of bicalutamide 150 mg in this situation may have a positive impact too on progression free survival. In case of lymph node involvement, androgen deprivation is the standard treatment with an overall survival benefit. The place of local radiation therapy is still debating. PMID- 17845995 TI - [New targeted therapies in hormone-refractory prostate cancer]. AB - Although the number of men presenting with metastatic prostate cancer has decreased significantly over the last several years, the death rate for those men is essentially unchanged. Effective treatments have not existed for prostate cancer progressing after androgen deprivation therapy until recently. Docetaxel based chemotherapy has demonstrated to extend patient survival in two large randomized studies. These studies have provided the impetus to combine docetaxel with novel biologic drugs to further consolidate the gains in long-term outcome. With the arrival of new therapies such as epothilone analogues, small molecule receptor tyrosine kinase inhibitors, monoclonal antibodies, bone-targeted drugs, antisense oligonucleotides, antiangiogenics drugs and endothelin receptor antagonists, the future of prostate cancer therapy appears promising. PMID- 17845996 TI - [State of the art about new therapeutic vaccines in prostate cancer: dendritic cells, engineered tumor cells and recombinant virus]. AB - Therapeutic vaccines for prostate cancer were initially reported as limited with low immunological responses and uncertain clinical benefit. Recently, new methods become available, such preparations of well-characterized autologous dendritic cells, and use of gene therapy tools to increase whole-tumor cells or host tissue immunogenicity. These are able to enhance and diversify therapeutic options. Indeed, several vaccinal approaches are being investigated, including optimized mature dendritic cells, allogeneic genetically modified tumor cells, or viral vectors. Due to the description of immunological and clinical responses, large phase III randomized trials are now conducted. After summarizing the mechanistic basis for these approaches, this review describes the experience with the most recent and promising clinical studies and introduces short-term perspectives that could lead to improvement in healthcare offer for prostate cancer patients. PMID- 17845997 TI - [Molecular aspects of prostate cancer: recent data from the literature]. AB - A meta-analysis of recent data from the literature underscores the considerable body of present knowledge concerning prostate carcinogenesis, in part due to the numerous molecular biology tools now at our disposal. As concerns early events, much interest is being paid to modifications in the expression of GSTP1 and NKX3.1 occurring in totipotent stem cell populations. The discovery of fusion genes implicating TMPRSS2 and ERG (and, on rare occasions, other ETS family transcription factors) constitutes a major advance. Under physiological androgenic stimulation, the presence of these fusion genes leads to overexpression of genes involved in cell growth and differentiation. Concomitantly, alterations in numerous signalling pathways (growth factors, Wnt beta catenine, PI3K/Akt) are responsible for the onset of an aggressive tumor phenotype. Hormono-independence is currently explained by an amplification of, or mutations in, androgenic receptors. These are facilitated by genomic instabilities linked to alterations in proteins which regulate gene expression, such as EZH2, and by the influence of the tumor microenvironment. Disturbances in the interactions between tumor cells and the microenvironment contribute to local extension of the tumor. Changes in the expression of E-cadherin are responsible for modifications in cell adhesion to the extracellular matrix. The expression of metalloproteases and of angiogenic factors favors tumor dissemination. Finally, the bone tropism in prostate metastases is probably linked to osteomimetic properties of prostate tumor cells which are capable of expressing certain proteins involved in bone remodelling, such as Runx-2, BSP (bone sialoprotein) and BMP (bone morphogenetic protein). Numerous studies remain to be carried out in order to correlate the identified genetic profiles and molecular anomalies with tumor prognosis. Nevertheless, the possibility of decrypting these anomalies for use in therapeutic applications is encouraging. PMID- 17845998 TI - [Metastatic prostate cancer treatment in the elderly]. AB - Incidence and mortality of prostate cancer increase with age. This epidemiologic trend and disease's natural history, extending on 10 to 15 years, explain that a majority of patients are old (more than 70 years) to very old (more than 80 years) at the metastatic stage. Moreover, when a geriatric screening is done, oncogeriatric parameters are often disturbed, justifying both an oncologic and a geriatric approaches. But the strength of co-morbidities does not justify a systematic under-treatment, because a patient older than 70 years and suffering from prostate cancer on two will die from his cancer, often with a painful symptomatology. As for a younger patient, the disease is hormono-sensitive during 18 to 24 months, before it becomes androgeno-resistant. The treatment, simple castration, complete hormonal blocking or anti-androgens alone, was not evaluated specifically in the elderly. Clinical and biological response to hormonal manipulation is often short and this procedure should not delay chemotherapy, when patient's clinical status allows it, in order mainly to reduce clinical symptoms. Docetaxel showed, in TAX427 study, a better control of clinical symptoms than mitoxantrone and also an increase in patients'survival. In the subgroup of patients older than 70, hematologic toxicities are more frequent and justify a G-CSF prophylaxy, according to international recommendations; on the opposite, non-hematologic toxicities are as frequent as in the younger subgroup. When bone metastases are symtomatic, some treatments can associate or follow a chemotherapy: bisphosphonates, radiotherapy and metabolic radiotherapy. These treatments have specific toxicities and must be specifically supervised in the elderly (bisphosphonates can worsen a renal insufficiency and metabolic radiotherapy induces frequently a limitant hematotoxicity). Lastly, new molecules are currently under evaluation. Current or future studies, according to international recommendations, must include elderly patients and avoid restrictive exclusion criteria. PMID- 17845999 TI - [Angiogenesis]. PMID- 17846000 TI - [Hypoxia and angiogenesis]. AB - The presence of hypoxic regions within solid tumours is associated with a more malignant tumour phenotype and worse prognosis. To obtain a blood supply and protect against cellular damage and death, oxygen-deprived cells in tumours alter gene expression, resulting in resistance to therapy. Hypoxia is sensed at the cellular level, leading to the activation of molecular pathways to cope with this stress. The key mediator of hypoxia response is HIF1alpha, a member of the hypoxia-inducible factor (HIF) family of proteins. This protein is a transcription factor that stimulates the expression of a multitude of genes important for adaptation to hypoxia, including those encoding angiogenesis. Angiogenesis is stimulated by vascular endothelial growth factor (VEGF), a HIF target gene, to increase blood flow towards oxygen-deprived tissues. This regulation of angiogenesis by hypoxia and HIF is crucial during embryonic development, but also for recovery after ischemic injury. Angiogenesis is one of the physiological responses to hypoxia. Nevertheless, angiogenesis has also deleterious effects by favouring tumour growth. PMID- 17846001 TI - [Experimental approaches to study in vivo angiogenesis]. AB - Angiogenesis has become a major issue in oncology. Different in vivo angiogenesis assays have been developed in order to better understand fundamental aspects of vascular development or to investigate the effect of therapeutic molecules on blood vessel growth. In this article, we will briefly review the main in vivo angiogenesis assays relevant to oncology and discuss their advantages and disadvantages. PMID- 17846002 TI - [Genetics and angiogenesis: the example of von Hippel-Lindau disease]. AB - Von Hippel-Lindau (VHL) disease is the main cause of inherited kidney cancer and the model of tumoral angiogenesis. This rare syndrome is caused by germline mutations of the VHL tumor-suppressor gene that predispose to the development of a panel of highly vascularized tumors. Main manifestations include CNS and retinal haemangioblastomas, endolymphatic sac tumors, clear-cell renal cell carcinomas (RCC), phaeochromocytomas and pancreatic neuroendocrine tumors. The VHL gene plays a major role in regulation of the oxygen-sensing pathway by targeting the hypoxia-inducible factor HIF for degradation in proteasome. Somatic inactivation of the VHL gene occurs also in most sporadic RCC. Recent progress are pawing the way for the development of antiangiogenic targeted therapies that have already shown promising results in metastatic sporadic RCC. PMID- 17846003 TI - [Oral drugs inhibiting the VEGF pathway]. AB - Angiogenesis does not initiate malignancy but promotes tumor progression and metastasis. Inhibiting angiogenesis is now a validated strategy for treatment of cancer. In order to do it, different ways are under investigation from cellular therapy to oral agents. Nowadays targeting angiogenesis with small molecules mainly concern inhibition of the VEGF receptors tyrosine kinase activity. Five molecules are currently in phase III trials and two of them (sunitinib and sorafenib) have been approved by the FDA for the treatment of advanced renal cancer. Despite those encouraging results, numerous points remain unclear. The toxicity profile seems to be favourable but long term effects could be problematic. Indeed, clinical trials have pointed out the role of VEGF pathway in the maintenance of numerous physiological functions. Moreover, none of the agents are specifically anti-angiogenic and the respective parts of the "off target" effects are difficult to evaluate. Simple and reliable surrogate markers of toxicity and efficacy are still lacking. PMID- 17846004 TI - [Are antiangiogenic antibodies universal for solid tumor?]. AB - After over 30 years of theorizing, the use of angiogenesis inhibitors as anticancer therapy has finally moved from the realm of research to reality. Normal adult vasculature is generally quiescent in nature, with endothelial cells dividing approximately every 10 years. In contrast, the growth of tumours requires constant vascular growth and remodelling in order for solid tumours to grow beyond 1-2 mm3 in size. Vascular endothelial growth factor (VEGF) and its receptors are key regulators of the process of angiogenesis, which make them attractive therapeutic targets. A multitude of VEGF-targeted inhibitory agents are currently being investigated for the treatment of cancer. This review article focuses on recent developments in the use of angiogenesis inhibitors for the treatment of breast, lung, and colorectal cancers. PMID- 17846005 TI - [Angiogenesis and radiotherapy (vessels, anaemia, oxygen and radiosensitivity)]. AB - Oxygen plays a direct role in cell death after exposure to ionizing radiations and tumour hypoxia, favoured by anaemia, is a factor of poor treatment response. Tumour phenotype is directly influenced by tissue oxygenation, inducing tumour cells adaptation to the environment and potential resistance to treatment. The correction of tumour hypoxia can increase treatment response. It is however difficult to directly correlate pO2 and vascularisation. Vessels from angiogenesis get endothelial cells but have lost the functions of normal vessels (receptors, muscles...). The role of angiogenesis has been demonstrated on initial tumour growth and on metastatic potential and regulation. Many pre clinical studies have demonstrated the benefit of combining anti angiogenic compounds and cytotoxic agents (chemotherapy drugs and ionizing radiations). Clinical studies are on going and new evaluation models of treatment response will be necessary. PMID- 17846006 TI - [Angiogenesis and breast cancer]. AB - The growth of breast cancers, as is the case in other solid tumors, is dependent on the development of neo-vessels. This has been clearly demonstrated in preclinical models and clinical-biological studies. Yet, the biological mechanisms involved in angiogenesis are heterogeneous; pathways activated by vascular endothelial growth factor (VEGF) seem to play a prominent role in the early stages of the disease, whereas a number of other pathways are involved in the development of progressive and metastatic tumors. This might account for the disappointing results of phase III studies of bevacizumab in breast cancer as compared with results reported in renal or colon cancers. The use of new drugs targeting other angiogenic factors and a better selection of patients eligible for treatment might improve these results. This is a review of the major biological and clinical data available on the critical role of angiogenesis in breast cancer. We will also review the different clinical studies reported to date in this area. PMID- 17846007 TI - [Anti-angiogenic treatment and colorectal cancer]. AB - For many years, oncology research has focused on the study of therapeutic agents able to target a different cell than a cancer cell. Tumor angiogenesis mediated by the vascular endothelial growth factor (VEGF) was one of the pathways investigated. The treatment of metastastic colorectal cancer has dramatically evolved. Overall survival has significantly improved, owing to the use in standard daily practice of irinotecan and oxaliplatin, combined with 5 fluorouracil (5FU) and leucovorin. This review summarizes efficacy and safety data of two antiangiogenic agents, bevacizumab (a monoclonal antibody inhibiting VEGF) and vatalanib (a tyrosine kinase inhibitor of VEGF), assessed in phase III trials in metastastic colorectal cancer. The efficacy of bevacizumab combined with 5FU-leucovorin +/- irinotecan based on overall survival data which was demonstrated in the first-line treatment of metastastic colorectal cancer in studies conducted in the US, has recently been demonstrated in the same indication based on progression survival when combined to oxaliplatin and a fluoropyrimidine (capecitabine or 5FU-leucovorin). Bevacizumab combined to infusion chemotherapy with 5FU-leucovorin with or without irinotecan is indicated, in Europe, in the first-line treatment of metastastic colorectal cancer. While in the US, prescription options are wider in the first-line treatment, it is combined to chemotherapies with a fluoropyrimidine +/- irinotecan or oxaliplatin, and in second line as well with fluoropyrimidine and oxaliplatin. Several questions regarding the optimal use of bevacizumab still remain to be answered in the treatment of metastastic colorectal cancer. Vatalanib has not shown benefit in this pathology. PMID- 17846008 TI - [Angiogenesis and lung cancer]. AB - Inhibition of specific processes essential for tumour vascular development is actually one of the key strategies for treatment of lung cancer, for which angiogenesis is consistently predictive of a poor prognosis. The most promising agents target the vascular endothelial growth factor (VEGF) pathway, either by preventing VEGF-receptor binding as bevacizumab or inhibiting downstream receptor signaling in endothelial cells. Combination of bevacizumab with standard first line chemotherapy in non-small cell lung cancer demonstrates a significant survival advantage comparing to chemotherapy alone, which provides the "proof of concept" for inhibition of angiogenesis in lung cancer. Development of small molecules inhibiting tyrosine kinase activity of VEGF-receptors is ongoing; many of them showed a single-agent activity but their most likely use will be in combination with chemotherapy or biological agents. Toxicity issues are of concern with the occurrence of fatal pulmonary hemorrhage after cavitation and necrosis of primary tumour, which requires appropriate selection of patients before treatment. A better understanding of the complex process of angiogenesis and of surrogate markers of treatment effect will improve our ability to design more effective therapies. PMID- 17846010 TI - [Angiogenesis and hematologic malignancy]. AB - Angiogenesis plays an important role in the progression of tumors. This relationship has been described in several hematologic malignancies. Vascular endothelial growth factor and basic fibroblast growth factor are predictors of poor prognosis in leukemia and non Hodgkin's lymphoma. Bone marrow microvessels were found increased in multiple myeloma, but also in lymphoma and in acute lymphoblastic leukemia. Microvessel density is correlated with decreased survival in myeloma patients and relapse or resistance to chemotherapy in lymphoma. New drugs with antiangiogenic activity such as bevacizumab (binding and inactivation of VEGF) or VEGF-tyrosine kinase inhibitors have shown promising results in phase 1 trials. It will therefore be a future challenge to integrate anti-angiogenesis agents in currently existing treatment protocols to improve the outcome of therapy. PMID- 17846009 TI - [Angiogenesis and renal cell carcinoma]. AB - Developments in the knowledge of molecular biology of renal cell carcinoma (RCC) over the past 20 years have been identified. Angiogenesis is playing a key role in the physiopathology of RCC. Von Hippel-Lindau (VHL) alterations, HIFalpha accumulation and vascular endothelial growth factor (VEGF) overexpression are important mediators of this process. Several stategies have been developped to target angiogenesis for the treatment of metastatic RCC. These include inhibition of VEGF receptors (inhibition of the tyrosine kinase activity) or binding to the VEGF protein. Several additional kinases inhibitions including PDGF receptors are also targeted. Sunitinib (SU11248) is an orally biovailable small molecule that has demonstrated superiority over interferon-alpha for the treatment of metastatic RCC. In a recent randomized phase III study conducted in 750 patients, the response rate to sunitinib was 31% and to interferon 6%. The median of progression free survival (PFS) was 11 months for sunitinib and 5 months for interferon (p < 0.001). Sorafenib (BAY43-9006) was found to inhibit Raf1, but also VEGFR2 and 3, Flt3, PDGFR-a and b and c-kit, has been tested in a phase III study against placebo after one prior systemic therapy. The median of the time to progression (TTP) for sorafenib was 24 weeks versus 12 weeks for patients in the placebo arm (p = 0,01). Other molecules tested in metastatic RCC will be presented including axitinib, pazopanib and bevacizumab. PMID- 17846011 TI - [Imaging and angiogenesis: DCE-US (dynamic contrast enhanced-ultrasonography)]. AB - The early and functional evaluation of new treatments in oncology is a main goal. At present, technical advances in Doppler ultrasonography allow the detection of neovascularization for superficial and deep malignant tumours in order to evaluate the efficiency of new treatments such as antiangiogenic molecules. Contrast agents injection improves the efficiency of this technique and developments of perfusion softwares optimize this detection. Slow flows in tumour microvessels can be detected. Treatment response using DCE-US (dynamic contrast enhanced-ultrasonography) can be early predicted based on changes in the vascularization before volume modification calculating perfusion parameters maximal as peak intensity, time to peak intensity, area under the curve, slope coefficient of wash-in. PMID- 17846012 TI - [Circulating endothelial cells: biomarkers for monitoring activity of antiangiogenic therapy]. AB - Tumor vessel formation is largely dependent on the recruitment of endothelial cells. Rare in healthy individuals, circulating endothelial cells (CEC) are shed from vessel walls and enter the circulation reflecting endothelial damage or dysfunction. Increased numbers of CEC have been documented in different types of cancer. Recent studies have suggested the role for CEC in tumor angiogenesis, but whose presence could also reflect normal endothelium perturbation in cancer. Originating from the bone marrow rather than from vessel walls, endothelial progenitor cells (EPC) are mobilized following tissue ischemia and may be recruited to complement local angiogenesis supplied by existing endothelium. Recently, studies in mouse models suggest that the circulating fraction of endothelial progenitors (CEP) is involved in tumor angiogenesis but their contribution is less clear in humans. The detection of CEC and CEP is difficult and impeded by the rarity of these cells. They may have important clinical implication as novel biomarkers susceptible to predict more efficiently and rapidly the therapeutic response to anti-angiogenic treatments. However, a methodological consensus would be necessary in order to correctly evaluate the clinical interest of CEC and CEP in patients. PMID- 17846013 TI - [Cutaneous side effects of antiangiogenic agents]. AB - Antiangiogenic agents can be associated with cutaneous side effects with a new and original spectrum of skin symptoms. A correlation between the molecular targets and skin manifestations is proposed. Further prospective studies are necessary in order to evaluate the potential association between skin side effects and clinical response. Systematic report and characterization of side effects occurring with new targeted therapies is critical. It will help us understanding better skin pathophysiology, but, most of all, it will lead to more efficient symptomatic treatment for our patients. PMID- 17846014 TI - Mixed valence complexes involving MM quadruple bonds (M=Mo or W). AB - The MM quadruple bond of configuration MM sigma2pi4delta2 is redox active and in many ways ideally suited for studies of mixed valency when two or more such centres are linked by a bridging ligand. In this account, the mechanism of electronic coupling is examined for complexes of the type [L3M2bridgeM2L3]0/+ where L, a pivalate; bridge, a dicarboxylate or related ligand and M, Mo or W. The represented examples allow us to probe electronic factors close to the class II/III border and readily distinguish between electron and hole transfer in the superexchange mechanism. The potential for mixed valence organic radical anions mediated by the M2 centre is also raised and one specific example of class III behaviour is described. PMID- 17846015 TI - Mixed valency in organic charge transfer complexes. AB - Mixed-valence (partial charge transfer state) and segregated stacking are the key factors for constructing organic metals. Here, we discuss the ionicity phase diagrams for a variety of charge transfer systems to provide a strategy for the development of functional organic materials (Mott insulator, semiconductor, superconductor, metal, complex isomer, neutral-ionic system, etc.). PMID- 17846017 TI - Patterns of disease progression and outcomes in a randomized trial testing ABVD alone for patients with limited-stage Hodgkin lymphoma. AB - BACKGROUND: In the National Cancer Institute of Canada Clinical Trials Group/Eastern Cooperative Oncology Group HD.6 trial, progression-free survival was better in patients randomized to therapy that included radiation, compared to doxorubicin (Adriamycin), bleomycin, vinblastine and dacarbazine (ABVD) alone. We now evaluate patterns of progression and subsequent outcomes of patients with progression. PATIENTS AND METHODS: After a median of 4.2 years, 33 patients have progressed. Two radiation oncologists determined whether sites of progression were confined within radiation fields. Freedom from second progression (FF2P) and freedom from second progression or death (FF2P/D) were compared. RESULTS: Reviewers agreed for the extended (kappa = 0.87) and involved field (kappa = 1.0) analyses. Progression after ABVD alone was more frequently confined within both the extended (20/23 vs. 3/10; P = 0.002) and involved fields (16/23 vs. 2/10; P = 0.02). There was no difference in FF2P between groups [5-year estimate 99% (radiation) versus 96% (ABVD alone)] [hazard ratio (HR) = 3.14, 95% confidence interval (CI) 0.63-15.6; P = 0.14]; the 5-year estimates of FF2P/D were 94% in each group (HR = 1.04, 95% CI 0.41-2.63; P = 0.93). CONCLUSION: Treatment that includes radiation reduces the risk of progressive Hodgkin lymphoma in sites that receive this therapy, but we are unable to detect differences in FF2P or FF2P/D. PMID- 17846016 TI - Phonetic learning as a pathway to language: new data and native language magnet theory expanded (NLM-e). AB - Infants' speech perception skills show a dual change towards the end of the first year of life. Not only does non-native speech perception decline, as often shown, but native language speech perception skills show improvement, reflecting a facilitative effect of experience with native language. The mechanism underlying change at this point in development, and the relationship between the change in native and non-native speech perception, is of theoretical interest. As shown in new data presented here, at the cusp of this developmental change, infants' native and non-native phonetic perception skills predict later language ability, but in opposite directions. Better native language skill at 7.5 months of age predicts faster language advancement, whereas better non-native language skill predicts slower advancement. We suggest that native language phonetic performance is indicative of neural commitment to the native language, while non-native phonetic performance reveals uncommitted neural circuitry. This paper has three goals: (i) to review existing models of phonetic perception development, (ii) to present new event-related potential data showing that native and non-native phonetic perception at 7.5 months of age predicts language growth over the next 2 years, and (iii) to describe a revised version of our previous model, the native language magnet model, expanded (NLM-e). NLM-e incorporates five new principles. Specific testable predictions for future research programmes are described. PMID- 17846018 TI - A phase II trial of S-1 and cisplatin in patients with metastatic or relapsed biliary tract cancer. AB - BACKGROUND: Optimal chemotherapy for advanced biliary tract cancer (BTC) is yet to be defined. We carried out this study to evaluate the efficacy and toxicity of combination chemotherapy with S-1 and cisplatin in metastatic or relapsed BTC. PATIENTS AND METHODS: Patients with pathologically proven BTC were eligible. The chemotherapy regimen consisted of S-1 (40 mg/m(2) p.o. b.i.d. from D1-14) and cisplatin (60 mg/m(2) on D1), repeated every 3 weeks. RESULTS: Fifty-one BTC patients (metastatic:relapsed = 37:14, Gall-bladder:intrahepatic bile ducts:extrahepatic bile ducts = 16:25:10) were enrolled from January 2005 to December 2006. Median age was 57 years (range, 31-71) and most patients had a good performance status. The overall response rate was 30% [95% confidence interval (CI), 17.3-42.7] and complete response was observed in two patients (4%), partial response in 13 (26%), stable disease in 21 (42%), and progressive disease in 9 (18%). With a median follow-up of 12.4 months, the median time to progression was 4.8 months (95% CI, 3.3-6.3) and median overall survival was 8.7 months (95% CI, 6.0-11.4). Major toxic effects were grade 3/4 neutropenia (8.9% of all cycles) and febrile neutropenia was observed in six cycles (2.7% of all cycles). CONCLUSION: Combination chemotherapy with S-1 and cisplatin was a moderately effective outpatient-based regimen in BTC patients. Toxic effects were moderate but manageable. PMID- 17846019 TI - Pegfilgrastim +/- ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study. AB - BACKGROUND: TAC (docetaxel/doxorubicin/cyclophosphamide) is associated with high incidences of grade 4 neutropenia and febrile neutropenia (FN). This analysis compared the efficacies of four regimens for primary prophylaxis of FN and related toxic effects in breast cancer patients receiving neoadjuvant TAC. PATIENTS AND METHODS: Patients with stage T2-T4 primary breast cancer were scheduled to receive 6-8 cycles of TAC. Primary prophylaxis was: ciprofloxacin 500 mg orally twice daily on days 5-14 (n = 253 patients; 1478 cycles), daily granulocyte colony-stimulating factor (G-CSF) (filgrastim 5 microg/kg/day or lenograstim 150 microg/m(2)/day) on days 5-10 (n = 377; 2400 cycles), pegfilgrastim 6 mg on day 2 (n = 305; 1930 cycles), or pegfilgrastim plus ciprofloxacin (n = 321; 1890 cycles). RESULTS: Pegfilgrastim with/without ciprofloxacin was significantly more effective than daily G-CSF or ciprofloxacin in preventing FN (5% and 7% versus 18% and 22% of patients; all P < 0.001), grade 4 neutropenia, and leukopenia. Pegfilgrastim plus ciprofloxacin completely prevented first cycle FN (P < 0.01 versus pegfilgrastim alone) and fatal neutropenic events. CONCLUSION: Ciprofloxacin alone, or daily G-CSF from day 5-10 (as in common practice), provided suboptimal protection against FN and related toxic effects in patients receiving TAC. Pegfilgrastim was significantly more effective in this setting, especially if given with ciprofloxacin. PMID- 17846020 TI - Optimizing clinical care of patients with metastatic breast cancer: a new oral vinorelbine plus trastuzumab combination. AB - BACKGROUND: Trastuzumab (T) combined with i.v. vinorelbine (i.v.VNR) is an active regimen for patients with advanced breast cancer (ABC). In order to further improve quality of life of patients undergoing treatment for ABC, a new regimen using oral vinorelbine (oVNR) (d1 + d3) plus q3wks T was tested (ToVNR). PATIENTS AND METHODS: Thirty-nine patients with ABC, human epidermal growth factor receptor 2/neu 3+ or FISH positive received 288 treatment cycles with T 6 mg/kg (loading dose, 8 mg/kg) on d1 and oVNR 55 mg/m(2) on d1 + d3, q3wks until disease progression or unacceptable toxicity. RESULTS: Thirty-seven patients and 286 treatment cycles were evaluated (two patients were lost to follow-up). Treatment was very well tolerated. Two patients had complete response (CR), 14 partial response (PR), 17 stable disease (SD) and four disease progression (PD) (overall response rate: 43%). Clinical benefit rate (CR + PR + SD >24 months) was 73%. Median time to progression was 8.9 months (range 2-27) and median duration of response was 10.9 months (range 2-27). CONCLUSIONS: The ToVNR combination is active and very well tolerated. It favorably compares with the combination of T and weekly i.v. administered VNR, allowing a more convenient once every three weeks hospital admission and leaving patients and care providers free from the unpleasant effect of i.v.VNR. PMID- 17846021 TI - A phase I and pharmacokinetic study of lapatinib in combination with infusional 5 fluorouracil, leucovorin and irinotecan. AB - BACKGROUND: This study determined the optimally tolerated regimen (OTR) of oral lapatinib administered in combination with infusional 5-fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) and assessed the safety, tolerability and pharmacokinetics of the combination. PATIENTS AND METHODS: Twenty-five patients were enrolled; 12 patients were treated at three dose levels to determine OTR; then 13 patients were treated at OTR to evaluate the pharmacokinetics of the combination. RESULTS: The 2-weekly OTR comprised lapatinib 1250 mg/day with irinotecan 108 mg/m(2) (day 1) and leucovorin 200 mg/m(2), 5-FU bolus 240 mg/m(2) and 5-FU infusion 360 mg/m(2) (days 1 and 2); doses of 5-FU and irinotecan represent a 40% reduction in dose compared to conventional FOLFIRI. Dose-limiting toxicities were grade 3 diarrhoea and grade 4 neutropenia. Co-administration of lapatinib increased the area under the plasma concentration-time curve of SN-38, the active metabolite of irinotecan, by an average of 41%; no other pharmacokinetic interactions were observed. Of 19 patients evaluable for disease response assessment, four patients had partial response and nine patients had stable disease. CONCLUSION: The combination of lapatinib and FOLFIRI is safe and demonstrates clinical activity; the documented PK interaction can effectively be compensated by lowering the doses of 5-FU and irinotecan. This regime may be further tested in a phase II trial. PMID- 17846022 TI - HLA-G expression in human ovarian carcinoma counteracts NK cell function. AB - BACKGROUND: Human leukocyte antigen-G (HLA-G) is an important immunotolerant which could be a part of the strategies applied by malignant cells applied to avoid host immunosurveillance. Aberrant expression of HLA-G has been found in ovarian carcinoma. The aim of this study was to evaluate the HLA-G expression in ovarian cancer tissues and to explore its function in vitro. MATERIALS AND METHODS: HLA-G expression in 33 primary ovarian carcinoma tissues was analyzed using immunohistochemistry with the anti-HLA-G monoclonal antibody (mAb) 4H84. Furthermore, the function of HLA-G in NK cell cytotoxicity was determined in vitro by cloning and expression of HLA-G on the ovarian carcinoma cell OVCAR-3. RESULTS: HLA-G expression was detected in 22/33 (66.7%) primary tumor tissues, but was absent in normal ovarian tissues (P<0.01). Cytotoxicity studies showed that HLA-G expression dramatically inhibits cell lyses by NK-92 cells (P<0.01), which could be restored by the anti-HLA-G conformational mAb 87G (P<0.01). CONCLUSION: HLA-G was expressed in a significant number of primary ovarian carcinoma tissues, and HLA-G expression in OVCAR-3 could directly inhibit NK-92 cell lysis. Taken together, our results indicated that expression of HLA-G plays an important role in evasion of ovarian cancer cells from host immunosurveillance. PMID- 17846023 TI - Current role of allogeneic stem cell transplantation in breast cancer. PMID- 17846024 TI - Prostate-specific antigen doubling time before onset of chemotherapy as a predictor of survival for hormone-refractory prostate cancer patients. AB - BACKGROUND: We evaluated the possible use of prostate-specific antigen doubling time (PSA-DT) before chemotherapy initiation as a surrogate marker of survival in hormone-refractory prostate cancer (HRPC) patients. PATIENTS AND METHODS: Data from 250 consecutive metastatic HRPC patients treated with chemotherapy between February 2000 and November 2006 were retrospectively analysed. At least three PSA assays were required within 3 months before chemotherapy. PSA-DT was calculated as ln 2 divided by the slope of the log PSA line, and the difference between two log PSA levels was divided by the time interval. The primary endpoint was overall survival (OS). Survival rates according to PSA-DT were stratified on chemotherapy regimen. Multivariate Cox regression analysis was performed to isolate the impact of PSA-DT on OS, controlling for associate prognostic covariates. RESULTS: Patients received docetaxel- (82%) or mitoxantrone-based chemotherapy. The median PSA-DT was 45 days (range 4.7-1108 days). There were 174 deaths (70%). The median survival was 16.5 months (95% confidence interval [CI] = 12.5-20.5) and 26.4 months (95% CI = 20.3-32.4) for patients with a PSA-DT < 45 and > or =45 days, respectively. In the multivariate setting, the adjusted hazard ratio (HR) was 1.39 (95% CI = 1.03-1.89; P = 0.04), stratified by chemotherapy regimen. CONCLUSION: A short PSA-DT before onset of chemotherapy in HRPC patients was associated with an increased risk of death. This could be useful as a stratification parameter in trials with new drugs in a metastatic setting. PMID- 17846025 TI - Management of venous port systems in oncology: a review of current evidence. AB - BACKGROUND: Over the last decades, many changes have occurred in oncology with new chemotherapy combinations and more complex application schemes becoming available. Central venous catheters and implantable venous port systems have become widely used and have facilitated the problem of vascular access. However, important complications are associated with permanent central venous catheters. MATERIAL AND METHODS: This review summarizes evidence on venous port system use published in Medline up to February 2007. Moreover, recent guidelines for the prevention and management of catheter-related infections issued by the Infectious Diseases Society of America, the American College of Critical Care Medicine, the Society for Healthcare Epidemiology of America, the Center for Disease Control and Prevention, Atlanta, and the Infectious Diseases Working Party of the German Society of Hematology and Oncology are included. RESULTS: Sterile precautions are essential when implanting and accessing port systems. Infections must be treated with adequate antimicrobial therapy. Catheter-related thromboembolic complications were found at a rate of 12-64% in retrospective studies. Five current clinical trials investigated the effect of prophylactic anticoagulation with either low molecular weight heparin or warfarin in cancer patients with central venous devices. On the basis of these results, routine anticoagulation cannot be recommended. CONCLUSIONS: This article reviews the current literature on long-term complications of venous port systems, focusing on infection and thrombosis. In addition, it summarizes the evidence regarding routine maintenance of port systems in follow-up care. PMID- 17846026 TI - Comparing different error-conditions in film dosemeter evaluation. AB - In the evaluation of a film used as a personal dosemeter it may be necessary to mark the dosemeters when possible error-conditions are recognised, such as errors that have an influence on the ability to make a correct evaluation of the dose value. In this project a comparison has been carried out to examine how two individual monitoring services, IMS [National Institute of Radiation Hygiene, Denmark (NIRH) and National Research Centre for Environment and Health, Germany (GSF)], from two different EU countries mark their dosemeters. The IMS are different in size, type of customers and issuing period, but both use films as their primary dosemeters. The error-conditions examined are dosemeters exposed to moisture or light, contaminated dosemeters, films exposed outside the badge, missing filters in the badge, films inserted incorrectly in the badge and dosemeters not returned or returned too late to the IMS. The data are collected for the year 2003 where NIRH evaluated approximately 50,000 and GSF approximately 1.4 million film dosemeters. The percentage of film dosemeters is calculated for each error-condition as well as the distribution among eight different employee categories, i.e. medicine, nuclear medicine, nuclear industry, industry, radiography, laboratories, veterinary and others. It turned out, that incorrect insertion of the film in the badge was the most common error-condition observed at both IMS and that veterinarians, as the employee category, generally have the highest number of errors. NIRH has a significantly higher relative number of dosemeters in most error-conditions than GSF, which perhaps reflects that a comparison is difficult due to different systemic and methodical differences between the IMS and countries, e.g. regulations and monitoring programs etc. Also the non-existence of a common categorisation method for employee categories contributes to make a comparison like this difficult. PMID- 17846027 TI - Simulated and measured Hp(10) response of the personal dosemeter Seibersdorf. AB - The Hp(10) energy response of the personal dosemeter Seibersdorf and its two different filtered LiF:Mg,Ti (TLD-100) thermoluminescence (TL) detectors are investigated. A close-to-reality simulation model of the personal dosemeter badge including the wrapped detector card was implemented with the MCNP Monte Carlo N particle transport code. The comparison of measured and computationally calculated response using a semi-empirical TL efficiency function is carried out to provide information about the quality of the results of both methods, experiment and simulation. Similar to the experimental calibration conditions, the irradiation of dosemeters centred on the front surface of the International Organization for Standardization (ISO) water slab phantom is simulated using ISO 4037 reference photon radiation qualities with mean energies between 24 keV and 1.25 MeV and corresponding ISO conversion coefficients. The comparison of the simulated and measured relative Hp(10) energy responses resulted in good agreement within some percent except for the filtered TL element at lower photon energies. PMID- 17846028 TI - A new neutron monitor and extended conversion coefficients for HP(10). AB - A new personal dose equivalent monitor for neutrons, the 'HpSLAB', is introduced. The device consists of a 30x30x15 cm3 polymethyl-methacrylate slab hosting a superheated drop detector embedded at a depth of 10 mm. The personal dose equivalent monitor was characterised experimentally with fast neutron calibrations in the 0.144-14.8 MeV range and numerically with Monte Carlo simulations. In order to evaluate the performance of the device, its response was compared to the fluence-to-directional dose equivalent conversion coefficients, hp(10;alpha,E). Since published coefficients only cover neutron angles of incidence up to 75 degrees, a new extended set of coefficients was computed for angles of incidence up to 180 degrees. The method used in these calculations was the very same used in the generation of the dose equivalent coefficients recommended by International Commission on Radiological Protection publication 74. The response of the HpSLAB follows with good approximation the trend of the conversion coefficients for monoenergetic neutrons above approximately 0.5 MeV. The device was extensively tested in broad-spectrum workplace-fields encountered at nuclear installations and its response was on average within a factor 1.4 of the reference personal dose equivalent values, regardless of angle and energy distribution of the neutron fluence. PMID- 17846029 TI - Esorex 2005. AB - The European Study on Occupational Radiation Exposure called ESOREX was initiated by the European Commission in the 1997 year. The objectives of this European study are: (1) to provide the European Commission and the national competent radiation protection authorities with reliable information on how personal radiation monitoring, reporting and recording of dosimetric results is structured in European countries; (2) to collect reliable and directly comparable data on individual and collective radiation exposure in all occupational sectors where classified workers are employed. Therefore, it is important to receive information about the levels of individual personal radiation doses to workers in the different sectors and the trends and developments of these doses over a period of several years; (3) at present, all 25 European Union Member States, plus Bulgaria, Iceland, Norway, Romania and Switzerland, participate in the study; and (4) the study was executed under the leadership of German BfS in co operation with Czech SUJB. First results and analyses based on the data collected in the previous studies are presented in the paper 'Frasch, Petrova: Dose trends in occupational radiation exposure in Europe-Results from the ESOREX project'. As a result of a call for tender of the European Commission/DGTREN in the year 2003, the new ESOREX study called 'ESOREX2005' has been initiated. This study will end at the year 2007 and its main objectives are-to finalise the updating of the country-wise reports by describing the current situation in the field of occupational exposure control, evaluation and registration of personal doses of radiation workers and as a second part of the study, to collect dosimetric data for the period 2001-2005. PMID- 17846030 TI - Neutron area survey instrument measurements in the EVIDOS project. AB - Neutron survey instruments have been exposed at all the measurement locations used in the EVIDOS project. These results have an important impact in the interpretation of the results from the project, since operationally the survey instrument will be used for an initial assessment of and routine monitoring of the ambient dose equivalent dose rate. Additionally, since the response of these instruments is in some cases very well characterised, their systematic deviations from the reference quantities provide an important verification of the determination of those quantities. PMID- 17846031 TI - Exposure to galactic cosmic radiation and solar energetic particles. AB - Several investigations of the radiation field at aircraft altitudes have been undertaken during solar cycle 23 which occurred in the period 1993-2003. The radiation field is produced by the passage of galactic cosmic rays and their nuclear reaction products as well as solar energetic particles through the Earth's atmosphere. Galactic cosmic rays reach a maximum intensity when the sun is least active and are at minimum intensity during solar maximum period. During solar maximum an increased number of coronal mass ejections and solar flares produce high energy solar particles which can also penetrate down to aircraft altitudes. It is found that the very complicated field resulting from these processes varies with altitude, latitude and stage of solar cycle. By employing several active and passive detectors, the whole range of radiation types and energies were encompassed. In-flight data was obtained with the co-operation of many airlines and NASA. The EURADOS Aircraft Crew in-flight data base was used for comparison with the predictions of various computer codes. A brief outline of some recent studies of exposure to radiation in Earth orbit will conclude this contribution. PMID- 17846032 TI - Inter-rater agreement for a retrospective exposure assessment of asbestos, chromium, nickel and welding fumes in a study of lung cancer and ionizing radiation. AB - A retrospective exposure assessment of asbestos, welding fumes, chromium and nickel (in welding fumes) was conducted at the Portsmouth Naval Shipyard for a nested case-control study of lung cancer risk from external ionizing radiation. These four contaminants were included because of their potential to confound or modify the effect of a lung cancer-radiation relationship. The exposure assessment included three experienced industrial hygienists from the shipyard who independently assessed exposures for 3519 shop/job/time period combinations. A consensus process was used to resolve estimates with large differences. Final exposure estimates were linked to employment histories of the 4388 study subjects to calculate their cumulative exposures. Inter-rater agreement analyses were performed on the original estimates to better understand the estimation process. Although concordance was good to excellent (78-99%) for intensity estimates and excellent (96-99%) for frequency estimates, overall simple kappa statistics indicated only slight agreement beyond chance (kappa < 0.2). Unbalanced distributions of exposure estimates partly contributed to the weak observed overall inter-rater agreement. Pairwise weighted kappa statistics revealed better agreement between two of the three panelists (kappa = 0.19-0.65). The final consensus estimates were similar to the estimates made by these same two panelists. Overall welding fume exposures were fairly stable across time at the shipyard while asbestos exposures were higher in the early years and fell in the mid-1970s. Mean cumulative exposure for all study subjects was 520 fiber-days cc( 1) for asbestos and 1000 mg-days m(-3) for welding fumes. Mean exposure was much lower for nickel (140 microg-days m(-3)) and chromium (45 microg-days m(-3)). Asbestos and welding fume exposure estimates were positively associated with lung cancer in the nested case-control study. The radiation-lung cancer relationship was attenuated by the inclusion of these two confounders. This exposure assessment provided exposure estimates that aided in understanding of the lung cancer-radiation relationship at the shipyard. PMID- 17846033 TI - Bar workers' exposure to second-hand smoke: the effect of Scottish smoke-free legislation on occupational exposure. AB - OBJECTIVES: To examine changes in bar workers' exposure to second-hand smoke (SHS) over a 12-month period before and after the introduction of Scottish smoke free legislation on the 26 March 2006. METHODS: A total of 371 bar workers were recruited from 72 bars in three cities: Aberdeen, Glasgow, Edinburgh and small towns in two rural regions (Borders and Aberdeenshire). Prior to the introduction of the smoke-free legislation, we visited all participants in their place of work and collected saliva samples, for the measurement of cotinine, together with details on work patterns, self-reported exposure to SHS at work and non-work settings and smoking history. This was repeated 2 months post-legislation and again in the spring of 2007. In addition, we gathered full-shift personal exposure data from a small number of Aberdeen bar workers using a personal aerosol monitor for fine particulate matter (PM(2.5)) at the baseline and 2 months post-legislation visits. RESULTS: Data were available for 371 participants at baseline, 266 (72%) at 2 months post-legislation and 191 (51%) at the 1-year follow-up. The salivary cotinine level recorded in non-smokers fell from a geometric mean of 2.94 ng ml(-1) prior to introduction of the legislation to 0.41 ng ml(-1) at 1-year follow-up. Paired data showed a reduction in non-smokers' cotinine levels of 89% [95% confidence interval (CI) 85-92%]. For the whole cohort, the duration of workplace exposure to SHS within the last 7 days fell from 28.5 to 0.83 h, though some bar workers continued to report substantial SHS exposures at work despite the legislation. Smokers also demonstrated reductions in their salivary cotinine levels of 12% (95% CI 3-20%). This may reflect both the reduction in SHS exposure at work and falls in active cigarette smoking in this group. In a small sub-sample of bar workers, full-shift personal exposure to PM(2.5), a marker of SHS concentrations, showed average reductions of 86% between baseline and 2 months after implementation of the legislation. CONCLUSIONS: Most bar workers have experienced very large reductions in their workplace exposure to SHS as a result of smoke-free legislation in Scotland. These reductions have been sustained over a period of 1 year. PMID- 17846034 TI - Is the current threshold level for screening for congenital hypothyroidism too high? An audit of the clinical evaluation, confirmatory diagnostic tests and treatment of infants with increased blood spot thyroid-stimulating hormone concentrations identified on newborn blood spot screening in Wales. PMID- 17846035 TI - A genotype calling algorithm for the Illumina BeadArray platform. AB - MOTIVATION: Large-scale genotyping relies on the use of unsupervised automated calling algorithms to assign genotypes to hybridization data. A number of such calling algorithms have been recently established for the Affymetrix GeneChip genotyping technology. Here, we present a fast and accurate genotype calling algorithm for the Illumina BeadArray genotyping platforms. As the technology moves towards assaying millions of genetic polymorphisms simultaneously, there is a need for an integrated and easy-to-use software for calling genotypes. RESULTS: We have introduced a model-based genotype calling algorithm which does not rely on having prior training data or require computationally intensive procedures. The algorithm can assign genotypes to hybridization data from thousands of individuals simultaneously and pools information across multiple individuals to improve the calling. The method can accommodate variations in hybridization intensities which result in dramatic shifts of the position of the genotype clouds by identifying the optimal coordinates to initialize the algorithm. By incorporating the process of perturbation analysis, we can obtain a quality metric measuring the stability of the assigned genotype calls. We show that this quality metric can be used to identify SNPs with low call rates and accuracy. AVAILABILITY: The C++ executable for the algorithm described here is available by request from the authors. PMID- 17846036 TI - Clustal W and Clustal X version 2.0. AB - SUMMARY: The Clustal W and Clustal X multiple sequence alignment programs have been completely rewritten in C++. This will facilitate the further development of the alignment algorithms in the future and has allowed proper porting of the programs to the latest versions of Linux, Macintosh and Windows operating systems. AVAILABILITY: The programs can be run on-line from the EBI web server: http://www.ebi.ac.uk/tools/clustalw2. The source code and executables for Windows, Linux and Macintosh computers are available from the EBI ftp site ftp://ftp.ebi.ac.uk/pub/software/clustalw2/ PMID- 17846037 TI - Context-dependent clustering for dynamic cellular state modeling of microarray gene expression. AB - MOTIVATION: High-throughput expression profiling allows researchers to study gene activities globally. Genes with similar expression profiles are likely to encode proteins that may participate in a common structural complex, metabolic pathway or biological process. Many clustering, classification and dimension reduction approaches, powerful in elucidating the expression data, are based on this rationale. However, the converse of this common perception can be misleading. In fact, many biologically related genes turn out uncorrelated in expression. RESULTS: In this article, we present a novel method for investigating gene co expression patterns. We assume the correlation between functionally related genes can be strengthened or weakened according to changes in some relevant, yet unknown, cellular states. We develop a context-dependent clustering (CDC) method to model the cellular state variable. We apply it to the transcription regulatory study for Saccharomyces cerevisiae, using the Stanford cell-cycle gene expression data. We investigate the co-expression patterns between transcription factors (TFs) and their target genes (TGs) predicted by the genome-wide location analysis of Harbison et al. Since TF regulates the expression of its TGs, correlation between TFs and TGs expression profiles can be expected. But as many authors have observed, the expression of transcription factors do not correlate well with the expression of their target genes. Instead of attributing the main reason to the lack of correlation between the transcript abundance and TF activity, we search for cellular conditions that would facilitate the TF-TG correlation. The results for sulfur amino acid pathway regulation by MET4, respiratory genes regulation by HAP4, and mitotic cell cycle regulation by ACE2/SWI5 are discussed in detail. Our method suggests a new way to understand the complex biological system from microarray data. PMID- 17846038 TI - 2D NMR metabonomic analysis: a novel method for automated peak alignment. AB - MOTIVATION: Comparative metabolic profiling by nuclear magnetic resonance (NMR) is showing increasing promise for identifying inter-individual differences to drug response. Two dimensional (2D) (1)H (13)C NMR can reduce spectral overlap, a common problem of 1D (1)H NMR. However, the peak alignment tools for 1D NMR spectra are not well suited for 2D NMR. An automated and statistically robust method for aligning 2D NMR peaks is required to enable comparative metabonomic analysis using 2D NMR. RESULTS: A novel statistical method was developed to align NMR peaks that represent the same chemical groups across multiple 2D NMR spectra. The degree of local pattern match among peaks in different spectra is assessed using a similarity measure, and a heuristic algorithm maximizes the similarity measure for peaks across the whole spectrum. This peak alignment method was used to align peaks in 2D NMR spectra of endogenous metabolites in liver extracts obtained from four inbred mouse strains in the study of acetaminophen-induced liver toxicity. This automated alignment method was validated by manual examination of the top 50 peaks as ranked by signal intensity. Manual inspection of 1872 peaks in 39 different spectra demonstrated that the automated algorithm correctly aligned 1810 (96.7%) peaks. AVAILABILITY: Algorithm is available upon request. PMID- 17846039 TI - Construction of a reference gene association network from multiple profiling data: application to data analysis. AB - MOTIVATION: Gene expression profiling is an important tool for gaining insight into biology. Novel strategies are required to analyze the growing archives of microarray data and extract useful information from them. One area of interest is in the construction of gene association networks from collections of profiling data. Various approaches have been proposed to construct gene networks using profiling data, and these networks have been used in functional inference as well as in data visualization. Here, we investigated a non-parametric approach to translate profiling data into a gene network. We explored the characteristics and utility of the resulting network and investigated the use of network information in analysis of variance models and hypothesis testing. RESULTS: Our work is composed of two parts: gene network construction and partitioning and hypothesis testing using sub-networks as groups. In the first part, multiple independently collected microarray datasets from the Gene Expression Omnibus data repository were analyzed to identify probe pairs that are positively co-regulated across the samples. A co-expression network was constructed based on a reciprocal ranking criteria and a false discovery rate analysis. We named this network Reference Gene Association (RGA) network. Then, the network was partitioned into densely connected sub-networks of probes using a multilevel graph partitioning algorithm. In the second part, we proposed a new, MANOVA-based approach that can take individual probe expression values as input and perform hypothesis testing at the sub-network level. We applied this MANOVA methodology to two published studies and our analysis indicated that the methodology is both effective and sensitive for identifying transcriptional sub-networks or pathways that are perturbed across treatments. PMID- 17846040 TI - Correlations between cyclooxygenase-2 expression and angiogenic factors in primary tumors and liver metastases in colorectal cancer. AB - BACKGROUND: Angiogenesis is required for growth and metastasis of colorectal cancer (CRC), and several positive regulators of tumor angiogenesis have been identified. Cyclooxygenase-2 (COX-2), known to be elevated in several human cancers, regulates angiogenesis by inducing angiogenic factors. The aim of this study was to clarify the levels and evaluate the relationships of COX-2, vascular endothelial growth factor A and C, thymidine phosphorylase (TP) and microvascular density (MVD) in paired tissue specimens between primary CRC and corresponding metastatic liver cancer. METHODS: Tissue samples from pairs of primary tumors and corresponding metastatic liver tumors from 44 patients with CRC were immunohistochemically evaluated for COX-2, VEGF-A, VEGF-C, TP and MVD. RESULTS: The primary and corresponding metastatic liver tumors tended to show concordant immunoreactivity for COX-2 (P = 0.005, rs = 0.428), VEGF-A (P = 0.039, rs = 0.314), TP (P = 0.005, rs = 0.422) and MVD (P = 0.046, rs = 0.304) by Spearman rank test. The rate of COX-2 immunoreactivity was higher in liver metastases than in primary tumors (P = 0.002), while the rate of VEGF-A was higher in primary tumors than in liver metastases (P = 0.0004). The incidence of TP immunoreactivity and the level of MVD did not differ between primary and metastatic liver tumors (P = 0.247; P = 0.229). Significant correlations were found between COX-2 immunoreactivity and VEGF-A immunoreactivity in metastatic liver tumors (P = 0.033) as well as in primary tumors (P = 0.008). CONCLUSION: The positive correlations between COX-2, VEGF-A, TP and MVD in primary CRC and liver metastasis as demonstrated here will help to predict the angiogenic activity of liver metastasis by analyzing primary tumors, allowing for individualized cancer treatment options. PMID- 17846041 TI - Brief report: children's responses to trauma- and nontrauma-related hospital admission: a comparison study. AB - OBJECTIVE: This study aims to investigate and compare psychological responses in children and parents 1 month after trauma- and nontrauma-related hospital admission. METHODS: Two hundred and five children aged 7-16 years (and their parents) were assessed for posttraumatic stress disorder (PTSD), other psychopathology, and distress 1 month after trauma-related (Trauma Group; n = 101) and nontrauma-related hospital admission (Non-Trauma Group; n = 104). RESULTS: Clinically elevated PTSD symptom levels were more prevalent in children admitted for trauma-related (18%) than nontrauma-related reasons (4%). Parents also experienced posttraumatic distress, although rates of clinically elevated symptom levels did not differ between the Trauma (11%) and Non-Trauma (8%) groups. Other pathology and distress in children and parents were comparable across groups. CONCLUSIONS: Children experienced greater posttraumatic distress following trauma-related hospital admission, while parents' experience of their child's hospitalization is equally distressing regardless of the reason for admission. PMID- 17846043 TI - Hyperglycaemia and the outcome of stroke. PMID- 17846042 TI - Evidence-based assessment of adherence to medical treatments in pediatric psychology. AB - OBJECTIVES: Adherence to medical regimens for children and adolescents with chronic conditions is generally below 50% and is considered the single, greatest cause of treatment failure. As the prevalence of chronic illnesses in pediatric populations increases and awareness of the negative consequences of poor adherence become clearer, the need for reliable and valid measures of adherence has grown. METHODS: This review evaluated empirical evidence for 18 measures utilizing three assessment methods: (a) self-report or structured interviews, (b) daily diary methods, and (c) electronic monitors. RESULTS: Ten measures met the "well-established" evidence-based (EBA) criteria. CONCLUSIONS: Several recommendations for improving adherence assessment were made. In particular, consideration should be given to the use of innovative technologies that provide a window into the "real time" behaviors of patients and families. Providing written treatment plans, identifying barriers to good adherence, and examining racial and ethnic differences in attitudes, beliefs and behaviors affecting adherence were strongly recommended. PMID- 17846044 TI - Responsiveness of patient reported outcomes including fatigue, sleep quality, activity limitation, and quality of life following treatment with abatacept for rheumatoid arthritis. AB - OBJECTIVE: To evaluate the responsiveness of patient reported outcomes (PROs), including fatigue, sleep, activity limitation, and quality of life, in patients with rheumatoid arthritis (RA). METHODS: Data were considered from a randomised controlled trial comparing abatacept (n = 258) with placebo (n = 133) on a background of DMARD treatment in RA patients who were inadequate responders to anti-TNF therapy (ATTAIN study). PROs assessed included SF-36, activity limitation, fatigue, and sleep. For each outcome the treatment difference, relative per cent improvement, standardised response mean (SRM), and relative efficiency for assessing an outcome's ability to detect a treatment effect relative to tender joint count (TJC) were calculated. A relative efficiency >1 suggests a measure that is more efficient than TJC in detecting treatment effect. RESULTS: Moderate to large SRMs (>or=0.6) were observed for the PRO measures. In particular, SRMs (95% confidence interval) were: physician global, 0.72 (0.51 to 0.94); HAQ, 0.63 (0.42 to 0.85); SF-36 physical component score, 0.62 (0.40 to 0.83); SF-36 bodily pain, 0.68 (0.46 to 0.90); and fatigue, 0.59 (0.38 to 0.81). Relative efficiencies for physician global (1.6), SF-36 bodily pain domain (1.4), pain intensity (1.4), HAQ (1.2), SF-36 physical component score (1.2), fatigue (1.1), and patient global assessment (1.04) were all more responsive than TJC. The SF-36 mental component score (0.3), swollen joint count (0.6), activity limitation (0.8), sleep (0.7), and C reactive protein (0.9) were less responsive. CONCLUSIONS: Using PROs for evaluating treatments for RA can detect improvements and will identify changes that are important to patients. In general, physical assessments are more responsive to an effective treatment than mental assessments. PMID- 17846046 TI - Assessing the health of older adults with intellectual disabilities: a user-led approach. AB - Older adults with intellectual disability are at increased risk of a wide range of health problems. Hitherto, methods to assess these problems have been healthcare-professional-led and largely based on traditional medical models. Following a literature review and focus group work we produced a user-led health assessment that was feasible and acceptable. The assessment was administered to 57 adults with a wide range of intellectual disability aged 40 years and over, living in the community. The assessment took a median of 21 minutes to administer and covered user-led themes of participation/ability, nutrition and hygiene/self care. A principal component representing a user-led general health measure correlated positively with the number of health problems (rho = 0.54, p < 0.001) and the number of drugs (rho = 0.55, p < 0.001). Further studies using such user led assessments are needed to assess whether they can have a wider application. PMID- 17846047 TI - Assessing goal attainment for quality improvement. AB - Organizations that support persons with intellectual disabilities will likely experience increasing pressure to provide evidence of the benefits of services to participants in programs. In this article we propose a model for assessing goal attainment modified from scales used with other populations that both develops from the person-centered planning process and informs on program and organizational efficacy. Implications for assessing goal attainment and considerations for applying information to improve individual, program and organization quality are presented. PMID- 17846048 TI - Language, labels and diagnosis: an idiot's guide to learning disability. AB - The phrase 'learning disability' is just one in a long succession of descriptors applied to those people in our society who are categorized by a matrix of psycho medical assessments, marginalized by compromised intellectual function, characterized by increased health needs and excluded from the mainstream on the basis of reduced social opportunity. But what exactly is 'learning disability'? Is there an empirical basis to the label, or is it just another example of bureaucratic language objectifying individuals in a process of medicalization? Historical examples will be used to illustrate the origins of the taxonomy that has subsequently formed the basis of the labelling process. The more recent words of individuals labelled with learning disability too will be introduced to offer some grounding to the debate. Any apparent problem belongs to language more than science. Narrative approaches to understanding are suggested as a useful alternative to traditional scientific inquiry. PMID- 17846049 TI - Prevalence and influences on self-reported smoking among adolescents with mild learning disabilities, attention deficit hyperactivity disorder, and their typically developing peers. AB - Many adolescents take up the smoking habit despite its well-documented adverse health effects. This study explores the prevalence and influences on smoking among 89 adolescents with mild learning disabilities, 108 with attention deficit hyperactivity disorder (ADHD), and 124 typically developing peers aged 12-16 years. All the participants were attending mainstream secondary schools and they were asked to complete a self-report questionnaire on smoking. It was found that adolescents with ADHD smoked more than adolescents with mild learning disabilities, who in turned smoked more than adolescents not diagnosed with any disability. More adolescents with ADHD reported that the majority of their friends smoked and they were less well informed about the health effects of smoking. No differences were identified between the three groups in terms of the smoking behaviour of their parents and the perceived attitudes of their parents and friends towards smoking. Findings are discussed and suggestions are made for further research. PMID- 17846050 TI - An evaluation of positive behavioural support for people with very severe challenging behaviours in community-based settings. AB - This study employs a multiple baseline across individual design to describe positive behaviour support for five people in community settings. The individuals represent all people with intellectual disability residing in one county with long-standing challenging behaviour resulting in serious physical injury. Five types of outcome are presented: rates of behaviour, rates of medication, psychiatric symptomatology, quality of life and revenue costs. The systems of support required to maintain outcomes and develop real lifestyles include behaviour support planning, mental health review, on-call intensive support and emergency respite care. Behaviours reduced to near-zero levels following implementation of positive behaviour support and improvements were sustained over 24 months. The use of psychotropic medications reduced by 66 percent over the same period. Quality of Life Questionnaire scores improved significantly for three of the five participants. The results are discussed in the context of a framework for supporting people with severe challenging behaviours in the community. PMID- 17846051 TI - Cohort profile: the 1993 Pelotas (Brazil) birth cohort study. PMID- 17846052 TI - Response to commentary: maternal smoking during pregnancy hazard for what? PMID- 17846053 TI - Cohort profile: The Pacific Islands Families (PIF) Study. PMID- 17846054 TI - Is weak association between cigarette smoking and cardiovascular disease mortality observed in Japan explained by low total cholesterol? NIPPON DATA80. AB - BACKGROUND: An international comparison has indicated that the association between smoking and cardiovascular disease (CVD) differs according to total cholesterol (TC) levels. However, little has been published about the relationship between smoking and CVD mortality among populations with various cholesterol levels. METHODS: We calculated the adjusted relative hazard (RH) of smoking for CVD mortality among 8912 Japanese individuals without a history of stroke or heart disease, who were separated according to TC levels of >or=5.40, 4.81-5.39, 4.26-4.80 and <4.25 mmol/l into groups Q4, Q3, Q2 and Q1, respectively. The P-values for multiple interactions between TC and smoking status for CVD mortality were calculated using TC as a continuous variable, dichotomized smoking status (never vs current), and by including cross-product terms in the regression models. RESULTS: After 19 years of follow-up, 313 men and 291 women died of CVD. The RH of CVD mortality among men who currently smoked compared with those who never smoked was increased with higher TC (RH = 2.36 in Q4) and decreased in those with lower TC (RH = 0.85 in Q1) (interaction, P < 0.01). The profiles for coronary heart disease (CHD) mortality and ischaemic CVD (composite endpoint of CHD and ischaemic stroke) in men and for ischaemic CVD mortality in women were identical. The interaction might be explained by a biological mechanism and by frailty of those who have never smoked with lower TC. CONCLUSIONS: Counteractive measures should be implemented against smoking targeted towards Japanese with elevated TC levels. PMID- 17846055 TI - Cohort Profile: Caribbean, Central and South America Network for HIV research (CCASAnet) collaboration within the International Epidemiologic Databases to Evaluate AIDS (IeDEA) programme. PMID- 17846056 TI - Venous thromboembolism in association with features of the metabolic syndrome. AB - BACKGROUND: Central obesity, diabetes mellitus, dyslipidaemia and chronic hypertension--features of the metabolic syndrome--have been individually associated with venous thromboembolism (VTE). However, whether each of these factors additively increases the risk of VTE is uncertain. AIM: To determine whether features of the metabolic syndrome independently increase the risk of VTE. DESIGN: Prospective cohort study derived from the Heart Outcomes Prevention Evaluation 2 (HOPE-2) randomized clinical trial. SETTING: One hundred and forty five clinical centres in 13 countries. METHODS: We studied 5522 adults aged > or =55 years with cardiovascular disease or diabetes mellitus. At enrollment, 35% had 0-1 features of the metabolic syndrome, 30% had two, 24% had three and 11% had four. We defined symptomatic VTE as an objectively confirmed new episode of deep-vein thrombosis or pulmonary embolism. RESULTS: VTE occurred in 88 individuals during a median 5.0 years of follow-up. The incidence rate of VTE (per 100 person-years) was 0.30 with 0-1 features, 0.36 with two features, 0.38 with three features and 0.40 with four features of the metabolic syndrome (trend p = 0.43). Relative to the presence of 0-1 features of the metabolic syndrome, the adjusted hazard ratio (95%CI) for VTE was 1.22 (0.71-2.08) with two features, 1.25 (0.70-2.24) with three features, and 1.26 (0.59-2.69) with four features. DISCUSSION: The number of features of the metabolic syndrome present was not a clinically important risk factor for VTE in older adults with vascular arterial disease. PMID- 17846058 TI - Catheter-related sepsis in dialysis patients. PMID- 17846059 TI - Multiple myeloma: causes and consequences of delay in diagnosis. AB - BACKGROUND: Myeloma is a serious and usually fatal haematological malignancy with reported mortality of 10-20% within the first 2 months of presentation. Symptoms are non-specific, and patients thus present to a range of medical practitioners. AIM: To analyse the causes and consequences of a delay in diagnosis of myeloma. DESIGN: Retrospective case review. METHODS: The number and type of disease related complications present at diagnosis of 92 patients with myeloma were categorized according to the medical practitioner to whom the patient initially presented, the time before diagnosis and the status of the patient at study end in 2006. Overall and disease-free survival were analysed. RESULTS: Duration of symptoms >6 months prior to diagnosis was seen in 40% of the patients, of whom >50% had initially consulted a general practitioner. The most common presenting symptom (67%) was bone pain. The most common complications present at diagnosis were anaemia (54%), bone disease (45%) and renal failure (36%), with the highest frequency of complications in the group experiencing symptoms for >6 months. All patients in this group had two or more complications, while 40% in the group with symptoms for <3 months had no complications. A prolonged time to diagnosis had a significant effect on disease-free survival from both onset of first symptoms (p = 0.043) and from diagnosis (p = 0.003), but not on overall survival. DISCUSSION: A prolonged delay before diagnosis is associated with a significant impact on the clinical course of multiple myeloma. There is a need to raise awareness of the presentation of this condition, especially among general practitioners. PMID- 17846060 TI - Risk factors for anticoagulation-related bleeding complications in patients with atrial fibrillation: a systematic review. AB - Atrial fibrillation (AF) is associated with an increased stroke risk that may be reduced by therapeutic anticoagulation. However, anticoagulation is associated with an increased risk of bleeding that in some patients may outweigh the benefits in reducing the risk of stroke. We systematically reviewed the literature for risk factors of anticoagulation-related bleeding complications in patients with AF, as part of the formulation of recently published national guidelines for the management of AF. We identified nine studies that reported anticoagulation-related bleeding complications in AF patients. The following patient characteristics were identified as having supporting evidence for being risk factors for anticoagulation-related bleeding complications: advanced age, uncontrolled hypertension, history of myocardial infarction or ischaemic heart disease, cerebrovascular disease, anaemia or a history of bleeding, and the concomitant use of other drugs such as antiplatelet agents. The presence of diabetes mellitus, controlled hypertension and gender were not identified as significant risk factors. Some of the risk factors for anticoagulation-related bleeding are also indications for the use of anticoagulants in AF patients. There is a need for further research in this area to help physicians to balance the risks and benefits of anticoagulation in AF patients. PMID- 17846061 TI - Relative tachycardia in patients with sepsis: an independent risk factor for mortality. AB - BACKGROUND: Excess activation of the sympathetic nervous system may be a risk factor for mortality in patients with the systemic inflammatory response syndrome (SIRS) or sepsis. AIM: To examine whether excessive tachycardia, relative to the degree of fever is an independent risk factor for death in patients with SIRS. DESIGN: Prospective observational study. SETTING: Departments of medicine in three university hospitals in Israel, Germany and Italy. METHODS: We collected data for 3382 patients with SIRS, whether community- or hospital-acquired, 91% with sepsis, as part of an ongoing trial. RESULTS: Overall 30-day mortality was 12% (408/3382). The pulse/temperature ratio was significantly higher in patients who died than in survivors: mean +/- SD 2.55 +/- 0.57 vs. 2.40 +/- 0.48 bpm/ degrees C (p < 0.0001). Excessive tachycardia was significantly associated with a mortality in a logistic model accounting for other strong predictors of mortality (OR 1.54, 95%CI 1.10-2.17). Patients with septic shock were the only group for whom this association did not hold. DISCUSSION: Our data are compatible with the hypothesis that some patients with sepsis experience an excess activation of the sympathetic nervous system, leading to a fatal outcome. PMID- 17846062 TI - Sodium bicarbonate enhances membrane-bound and soluble human semicarbazide sensitive amine oxidase activity in vitro. AB - Semicarbazide-sensitive amine oxidase (SSAO) is a multifunctional enzyme with different biological roles that depend on the tissue where it is expressed. Because SSAO activity is altered in several pathological conditions, we were interested in studying the possible regulation of the human enzyme activity. It has been previously reported that SSAO activity is increased in the presence of Dulbecco's modified Eagle medium (DMEM) in vitro. The aim of the present work was to investigate the effects of the different constituents of DMEM on human SSAO activity. We found that sodium bicarbonate was the only component able to mimic the enhancement of both human aorta and plasma SSAO activity in vitro, suggesting a possible physiological role of bicarbonate as an intrinsic modulator of the human enzyme. Failure to take this activating effect into account could also result in inaccuracies in the reported tissue activities of this enzyme. PMID- 17846063 TI - CEL-I, an invertebrate N-acetylgalactosamine-specific C-type lectin, induces TNF alpha and G-CSF production by mouse macrophage cell line RAW264.7 cells. AB - Our previous studies demonstrated that CEL-I, an N-acetylgalactosamine (GalNAc) specific C-type lectin purified from the marine invertebrate Cucumaria echinata (Holothuroidea) showed potent cytotoxicity to several cell lines such as HeLa, MDCK and XC cells. In this study, we found that CEL-I induced increased secretion of tumour necrosis factor-alpha (TNF-alpha) and granulocyte colony stimulation factor (G-CSF) by mouse macrophage cell line RAW264.7 cells in a dose-dependent manner, whereas this cell line was highly resistant to CEL-I cytotoxicity. The cytokine-inducing activity of CEL-I was stronger than that of phytohaemagglutinin (PHA-L). A binding study using FITC-labelled CEL-I (F-CEL-I) indicated that the amount of bound F-CEL-I on RAW264.7 cells was greater than that of F-PHA-L, suggesting that the greater activity of CEL-I to induce cytokine secretion by RAW264.7 cells is partly due to the higher binding ability. Since the cell binding and cytokine-inducing activity of CEL-I were partly but significantly inhibited by the specific sugar (GalNAc), it is considered that the binding of CEL-I to cell-surface-specific saccharide moieties, which may be recognized by CEL-I with higher affinity than GalNAc, is essential for the induction of cytokine secretion. The secretion of TNF-alpha and G-CSF from CEL-I-treated RAW264.7 cells were almost completely prevented by brefeldin A (BFA), whereas increase in mRNA levels of these cytokines were not affected by BFA. Bio-Plex beads assay suggested that temporal increase in phosphorylation of extracellular regulated kinase (ERK), c-jun NH(2)-terminal kinase (JNK) and p38 MAP kinase occurred at relatively early time following CEL-I treatment. Furthermore, the secretion of TNF-alpha and G-CSF were inhibited by specific inhibitors for these MAP kinases. These results suggest that the intracellular signal transduction through the activation of MAP kinase system is involved in CEL-I-induced cytokine secretion. PMID- 17846064 TI - Characterization and crystallization of an IscU-type scaffold protein with bound [2Fe-2S] cluster from the hyperthermophile, aquifex aeolicus. AB - IscU plays a key role during iron-sulphur (Fe-S) cluster biosynthesis as a scaffold for the assembly of a nascent, highly labile Fe-S cluster. Here we report the characterization of an IscU-type protein (Aa IscU) from the hyperthermophilic bacterium Aquifex aeolicus. Unlike other known homologues of IscU, expression of Aa IscU in Escherichia coli has yielded an Fe-S cluster containing holo-protein. Biochemical and spectroscopic studies of the wild-type Aa IscU and its Asp38-to-Ala substituted (D38A) variant molecule indicate that the holo-protein forms a trimer containing substoichiometric [2Fe-2S] cluster with its stability substantially increased by a D38A substitution. The [2Fe-2S] cluster was oxygen-labile and upon loss of the cluster, the resultant apo-form dissociated into a smaller species, a mixture of monomer and dimer with the dimer form predominating. Reddish-brown crystals of holo-Aa IscU-D38A were obtained under anaerobic conditions, that gave diffractions beyond 2.0 A resolution with synchrotron radiation. The crystal belongs to the space group P2(1)2(1)2 with unit-cell parameters a = 72.6, b = 122.3, c = 62.4 A, where the asymmetric unit contains three molecules of Aa IscU. Successful crystallization of holo-Aa IscU D38A strongly suggests that the trimer association carrying substoichiometric [2Fe-2S] cluster represents a conformationally stable oligomeric state. PMID- 17846065 TI - The carboxyl-terminal region of the geranylgeranyl diphosphate synthase is indispensable for the stabilization of the region involved in substrate binding and catalysis. AB - Rat geranylgeranyl diphosphate synthase (GGPS) and its deletion mutants from the carboxyl terminus were analysed using Escherichia coli harbouring pACYC-crtIB, which contains crtI and crtB encoding the carotenoid biosynthetic enzymes. Mutants (delta-4, -8, -12 and -16) produced lycopene-derived red colour, but mutants (delta-17, -18, -19, -20, -23, -57 and -70) did not. The histidine-tagged mutants (delta-4, -8, -12 and -16) were overexpressed in E. coli BL21 (DE3) and purified in a stable form by nickel affinity chromatography except for one mutant (delta-16). The farnesyl-transferring activities of wild-type GGPS, delta-4, -8 and -12 mutants were relatively in a ratio of 1.0, 0.84, 0.26 and 0.0015. Each Km value of the four recombinants were estimated to be 0.71, 2.0 2.8 and 55 microM for farnesyl diphosphate and to be 2.9, 5.1, 56 and >100 microM for isopentenyl diphosphate, respectively. Allylic substrate specificities of these recombinants were estimated by quantitative analysis of the products, revealing that delta-8 and -12 mutants lack the ability to accept dimethylallyl and geranyl diphosphates compared to wild-type GGPS and delta-4 mutant. These results suggest that the KMFTEENE residing on the carboxyl-terminal sequence of GGPS stabilizes the active region involved in the substrate binding and catalysis. PMID- 17846066 TI - Characterization of native myosin VI isolated from sea urchin eggs. AB - Myosin VI is a molecular motor that is ubiquitously expressed among eukaryotic cells, and thought to be involved in membrane trafficking and anchoring the organelle to actin cytoskeleton. Studies on myosin VI have been carried out using recombinant proteins, but native myosin VI has not been purified yet. Here we purified native myosin VI from sea urchin eggs and characterized its properties. We found that the native myosin VI was a monomeric and non-processive motor protein, and also showed that it moved toward the pointed end of F-actin. Ca2+ stimulated actin-activated MgATPase activity of the native myosin VI, while it lowered its motility on F-actin. Immunofluorescence microscopy showed that the myosin VI was translocated from the inner cytoplasm to the cortex after fertilization. Myosin VI may be involved in endocytic activities in fertilized eggs. PMID- 17846067 TI - Constraint-induced movement therapy in the treatment of the upper limb in children with hemiplegic cerebral palsy: a Cochrane systematic review. AB - BACKGROUND: Constraint-induced movement therapy (CIMT) is emerging as a treatment approach for children with hemiplegic cerebral palsy. It aims to increase spontaneous use of the affected upper limb and limit the effects of learned non use. This review evaluates the effectiveness of CIMT, modified CIMT or Forced use in the treatment of children with hemiplegic cerebral palsy. DESIGN AND METHODS: Systematic Cochrane Review. The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 3), MEDLINE (1966 to August Week 4 2006), CINAHL (1982 to July Week 3 2006), EMBASE (1980 to August 2006), PsychInfo (1985 to August Week 4 2006) and reference lists of all relevant articles were searched. Relevant randomized and controlled clinical trials were systematically reviewed. RESULTS: Three studies met the inclusion criteria. One randomized controlled trial (RCT) showed a trend for positive treatment effect favouring CIMT using the Dissociated Movement subscale of the Quality of Upper Extremity Skills Test. A clinically controlled trial demonstrated a significant treatment effect favouring modified CIMT using the Assisting Hand Assessment at two and six months. Another inconsistently reported trial showed a significant treatment effect at six weeks on the self-care component of the WeeFIM using Forced use. REVIEWERS' CONCLUSIONS: Given the limited evidence, the use of CIMT, modified CIMT and Forced use should be considered experimental in children with hemiplegic cerebral palsy. Further research using adequately powered RCTs, rigorous methodology and valid, reliable outcome measures is essential to provide higher level support of the effectiveness of CIMT for children with hemiplegic cerebral palsy. PMID- 17846068 TI - Pilot study of a neurophysiological dysphagia therapy for neurological patients. AB - OBJECTIVE: To investigate the success of a neurophysiological dysphagia therapy in patients with neurological disorders. DESIGN: A pre- and post-intervention group study. SETTING: Acute rehabilitation unit. SUBJECTS: Ten patients (swallowing rate <1/5 minutes, Fruhreha-Barthel Index <-150, tracheostomy as a result of a swallowing disorder) with dysphagia as a result of a head injury or cerebral haemorrhage. INTERVENTIONS: Therapy was given based on facio-oral tract therapy for three weeks (15 sessions of 1 hour each). MEASURES: The general scales used were the Fruhreha-Barthel Index and Coma Remission Scale. Measures of swallowing rate, alertness and swallowing ability were undertaken before, during and after the treatment sessions and at intervals of 30 minutes for 2 hours after the treatment sessions. RESULTS: On the treatment days, the therapy did not lead to an increase in swallowing rate, but did lead to a significant increase in alertness. After completion of a single treatment session, there was a statistically significant decrease in alertness and swallowing rate for 90 minutes. An increase in alertness (Fruhreha-Barthel Index and Coma Remission Scale), swallowing ability (measured using an endoscopic examination) and protection of the respiratory tract was observed over the entire therapy period. CONCLUSION: Facio-oral tract therapy led to a statistically significant increase in alertness during the treatment session and, over the entire therapy period, to an increase in swallowing rate, alertness and swallowing ability. The decrease in alertness following therapy sessions must be taken into account in planning rehabilitative measures. Further studies on larger populations as well as studies currently in progress should further elucidate the strategies employed to rehabilitate dysphagic patients. PMID- 17846069 TI - The effects of incremental speed-dependent treadmill training on postural instability and fear of falling in Parkinson's disease. AB - OBJECTIVE: To detect the effectiveness of incremental speed-dependent treadmill training on postural instability, dynamic balance and fear of falling in patients with idiopathic Parkinson's disease. DESIGN: Randomized controlled trial. SETTING: Ankara Education and Research Hospital, 2nd PM&R Clinic, Cardiopulmonary Rehabilitation Unit. SUBJECTS: Fifty-four patients with idiopathic Parkinson's disease in stage 2 or 3 of the Hoehn Yahr staging entered, and 31 patients (21 training, 10 control) had outcome data. INTERVENTIONS: Postural instability of patients with Parkinson's disease was assessed using the motor component of the Unified Parkinson's Disease Rating Scale (UPDRS), Berg Balance Test, Dynamic Gait Index and Falls Efficacy Scale. Twenty-one patients with Parkinson's disease participated in an eight-week exercise programme using incremental speed dependent treadmill training. Before and after the training programme, balance, gait, fear of falling and walking distance and speed on treadmill were assessed in both Parkinson's disease groups. MAIN MEASURES: Walking distance and speed on treadmill, UPDRS, Berg Balance Test, Dynamic Gait Index and Falls Efficacy Scale. RESULTS: Initial total walking distance of the training group on treadmill was 266.45 +/- 82.14 m and this was progressively increased to 726.36 +/- 93.1 m after 16 training session (P < 0.001). Tolerated maximum speed of the training group on treadmill at baseline was 1.9 +/- 0.75 km/h and improved to 2.61 +/- 0.77 km/h (P < 0.001). Berg Balance Test, Dynamic Gait Index and Falls Efficacy Scale scores of the training group were improved significantly after the training programme (P < 0.01). There was no significant improvement in any of the outcome measurements in the control group (P > 0.05). CONCLUSIONS: Specific exercise programmes using incremental speed-dependent treadmill training may improve mobility, reduce postural instability and fear of falling in patients with Parkinson's disease. PMID- 17846070 TI - The effect of exercise on hip muscle strength, gait speed and cadence in patients with total hip arthroplasty: a randomized controlled study. AB - OBJECTIVE: To evaluate the effect of home versus in-hospital exercise (under supervision) programmes on hip strength, gait speed and cadence in patients with total hip arthroplasty at least one year after operation. SETTING: Physical therapy and rehabilitation department. SUBJECTS: Twenty-six patients who had had a total hip arthroplasty operation 12-24 months prior to the study were enrolled. INTERVENTIONS: The patients were randomized into three groups: group 1 patients were assigned a home exercise programme, group 2 patients exercised under physiotherapist supervision in hospital, and group 3 served as the control group, with no specific intervention. The study duration was six weeks. MAIN MEASURES: Maximum isometric abduction torque of operated hip muscle, gait speed and cadence were measured before and after the study. RESULTS: Maximum isometric abduction torques of the hip abductor muscles improved in groups 1 and 2, but not in group 3 (30 +/- 12 to 38 +/- 11 ft.lb in group 1, 18 +/- 10 to 30 +/- 9.8 ft.lb in group 2). Gait speed improved from 67.8 +/- 23 to 74.35 +/- 24 m/min in group 1, from 48.53 +/- 4 to 56.7 +/- 5 m/min in group 2 and from 58.01 +/- 12 to 59.8 +/- 14 m/min in group 3. Cadence also improved, from 97.7 +/- 18 to 111 +/- 17 steps/min in group 1, from 90.75 +/- 6 to 104.75 +/- 7 steps/min in group 2, and from 87 +/- 16 to 88.22 +/- 16 steps/min in group 3. When the three groups were compared, group 2 showed the best improvement (P = 0.006) only in maximum isometric abduction torque. CONCLUSION: Our findings suggest that both home and supervised exercise programmes are effective one year after total hip arthroplasty. Home exercise programmes with close follow-up could be recommended. PMID- 17846071 TI - Decrease of hypertonia after continuous passive motion treatment in individuals with spinal cord injury. AB - OBJECTIVE: To examine the effect of ankle continuous passive motion on the reflex excitability and overall hypertonia of calf muscles in individuals with chronic spinal cord injury and without physical disabilities. DESIGN: Two-way repeated measure experimental design. SETTING: Inpatient rehabilitation department in general hospital. SUBJECTS: The spinal cord injury group comprised eight individuals with chronic complete spinal cord injury and the control group comprised eight healthy people without physical disabilities. An additional eight healthy people were recruited as the sham group. INTERVENTIONS: Each subject received 60 min of continuous passive motion on the ankle joint. MAIN MEASURES: The H-reflex of the soleus muscle was elicited by tibia nerve stimulation just before, immediately after, and 10 min after continuous passive motion. The Modified Ashworth Scale (MAS) score at the ankle joint was recorded for the spinal cord injury group just before and 10 min after continuous passive motion therapy. RESULTS. After 60 min of continuous passive motion of the ankle joint, the H-reflex amplitude at the soleus muscle was depressed in individuals with and without spinal cord injury (77.46 +/- 32.64%, P = 0.047 and 51.76 +/- 26.74% of initial, P<0.0001, respectively). This depression persisted up to 10 min after continuous passive motion only in individuals without spinal cord injury. In individuals with spinal cord injury, the median of MAS scores decreased from 2 to 1.25 after continuous passive motion. CONCLUSION: Sixty minutes of continuous passive motion of the ankle joint decreased reflex excitability and overall hypertonia in people with or without spinal cord injury. The depression of overall hypertonia persisted longer than the reflex excitability in people with spinal cord injury. PMID- 17846072 TI - Effects of acupuncture and sham acupuncture in addition to physiotherapy in patients undergoing bilateral total knee arthroplasty--a randomized controlled trial. AB - OBJECTIVE: To compare the acute effects of acupuncture with sham acupuncture on knee pain, range of motion and ambulation in patients with knee osteoarthritis undergoing bilateral total knee arthroplasty, when added to a standard postoperative physiotherapy programme. DESIGN: Prospective patient- and assessor blinded randomized controlled trial. SETTING: Acute inpatient physiotherapy department. PATIENTS: Thirty patients (24 women and 6 men) undergoing bilateral total knee arthroplasty were included for final analysis in the study. INTERVENTIONS: Both groups received a standard postoperative physiotherapy programme. Each patient was also given either 10 sessions of acupuncture or sham acupuncture within two weeks. MAIN OUTCOME MEASURES: The primary outcome measures were the levels of pain at rest and at maximum after exercise measured by the numeric pain rating scale. Other outcome measures included active and passive ranges of knee motion measured by standard goniometer, and ambulation measured by the timed up-and-go test. RESULTS: Thirty-six patients were recruited at the start of the study with 18 patients allocated to the acupuncture group and another 18 patients to the sham acupuncture group. On postoperative day 15, there were 30 patients with complete data; three patients in each group dropped out from the study. The mean differences (95% confidence interval (CI)) in overall averages of postoperative mean pain levels were 0.4 (-0.6 to 1.3) and -0.8 (-2.0 to 0.4) at rest and at maximum respectively. There were no significant differences in the active and passive ranges of knee motion and the time for the timed up-and-go test between the two groups. CONCLUSION: There is no difference between the acute effects of acupuncture and sham acupuncture in addition to standard postoperative physiotherapy programme in patients with knee osteoarthritis undergoing bilateral total knee arthroplasty. PMID- 17846073 TI - The effect of voluntary trunk rotation and half-field eye-patching for patients with unilateral neglect in stroke: a randomized controlled trial. AB - OBJECTIVE: To investigate the effectiveness of voluntary trunk rotation and half field eye-patching to treat patients with unilateral neglect in stroke. DESIGN: Pre-post, day 60 follow-up, single-blinded randomized controlled trial. SETTING: Single-centre inpatient rehabilitation hospital. SUBJECTS: Sixty subacute patients with right hemisphere stroke having unilateral neglect within eight weeks post stroke consented to participate between November 2003 and July 2005. They were randomly assigned to three comparison groups. INTERVENTIONS: Nineteen patients received daily experimental training in voluntary trunk rotation (TR) for 1 hour five times a week for 30 days. Twenty patients received the same kind of treatment together with half-field eye-patching (TR + EP). Fifteen patients in the control group received conventional training with the same contact time. MAIN OUTCOME MEASURES: Patients were assessed on days 0, 30 and 60 using the Behavioural Inattention Test, the Clock Drawing Test, and the Functional Independence Measure. RESULTS: No significant differences between voluntary trunk rotation (TR), voluntary trunk rotation and half-field eye-patching (TR + EP) and controls were found in functional performance and neglect measures at day 30 (P = 0.042-0.994) and follow-up (P = 0.052-0.911) at P = 0.005 using Bonferroni correction. CONCLUSIONS: The results of this study do not support the use of voluntary trunk rotation alone or with half-field eye-patching to improve functional performance or reduce unilateral neglect in subacute patients with stroke. PMID- 17846074 TI - Additional exercise for older subacute hospital inpatients to prevent falls: benefits and barriers to implementation and evaluation. AB - OBJECTIVE: To evaluate the clinical effectiveness and implementation of a falls prevention exercise programme for preventing falls in the subacute hospital setting. DESIGN: Randomized controlled trial, subgroup analysis. PARTICIPANTS: Patients of a metropolitan subacute/aged rehabilitation hospital who were recommended for a falls prevention exercise programme when enrolled in a larger randomized controlled trial of a falls prevention programme. METHODS: Participants in both the control and intervention groups who were recommended for the exercise programme intervention were followed for the duration of their hospital stay to determine if falls occurred. Participants had their balance, strength and mobility assessed upon referral for the exercise programme and then again prior to discharge. Participation rates in the exercise programme were also recorded. RESULTS: Intervention group participants in this subgroup analysis had a significantly lower incidence of falls than their control group counterparts (control: 16.0 falls/1000 participant-days, intervention: 8.2 falls/1000 participant-days, log-rank test: P = 0.007). However few differences in secondary balance, strength and mobility outcomes were evident. CONCLUSION: This exercise programme provided in addition to usual care may assist in the prevention of falls in the subacute hospital setting. PMID- 17846075 TI - The rapid resolution of depression and anxiety symptoms after lower limb amputation. AB - OBJECTIVE: To ascertain the course of depressive and anxiety symptoms shortly after amputation and again after a period of inpatient rehabilitation. DESIGN AND SETTINGS: A cohort study in inpatients admitted to a rehabilitation ward after lower limb amputation. SUBJECTS: One hundred and five successive admissions over a one-year period. INTERVENTIONS: Nil. MAIN MEASURES: Hospital Anxiety and Depression Scale (HADS) on admission and discharge with correlation to demographic and patient features. RESULTS: At admission, 28 (26.7%) and 26 (24.8%) patients had symptoms of depression and anxiety respectively. This dropped to 4 (3.8%) and 5 (4.8%) by time of discharge, a mean of 54.3 days later. These reductions were statistically significant, as was the association between patients having symptoms of both depression and anxiety (P < 0.001). Patient stay was longer in those with symptoms (depression, P < 0.03; anxiety P < 0.001). There was no association with level of amputation, success of limb-fitting, age or gender. Depressive symptoms were associated with presence of other medical conditions (P < 0.01) and anxiety scores with living in isolation (P < 0.05). CONCLUSION: Depression and anxiety are commonly reported after lower limb amputation and previously thought to remain high for up to 10 years. We have found that levels of both depression and anxiety resolve rapidly. It is possible that a period of rehabilitation teaching new skills and improving patient independence and mobility may modify the previous bleak outlook of amputees. This positive finding may be useful in the rehabilitation of even the most distressed of amputees. PMID- 17846076 TI - Apraxia of speech: how reliable are speech and language therapists' diagnoses? AB - OBJECTIVE: To discover how reliably speech and language therapists could diagnose apraxia of speech using their clinical judgement, by measuring whether they were consistent (intra-rater reliability), and whether their diagnoses agreed (inter rater reliability). DESIGN: Video clips of people with communication difficulties following stroke were rated by four speech and language therapists who were given no definition of apraxia of speech, no training, and no opportunity for conferring. SETTINGS: Videos were made of people following stroke in their homes. Ratings of the videos were carried out in the university lab under controlled conditions. SUBJECTS: Forty-two people with communication difficulties such as aphasia, apraxia of speech and dysarthria took part, and four specialist speech and language therapists acted as raters. MAIN MEASURE: Speech and language therapists' ratings of the presence and severity of apraxia of speech using videos. RESULTS: Intra-rater reliability was high for diagnosing (1) the presence of apraxia of speech (Cohen's kappas ranging from 0.90 to 1.00; 0.93 overall), and (2) the severity of apraxia of speech (kappa 0.84 to 0.92; 0.90 overall). The inter-rater reliability was also high for both the presence of apraxia of speech (kappa 0.86) and severity of apraxia of speech (0.74). CONCLUSION: Despite controversy over its nature and existence, specialist speech and language therapists show high levels of agreement on the diagnosis of apraxia of speech using their clinical judgement. PMID- 17846077 TI - Mid-term results of peripheric cannulation after port-access surgery. AB - Several minimally invasive approaches, avoiding median sternotomy, have been described within the last few years for cardiac surgery. Femoral arterial and venous cannulation for extracorporeal perfusion are required for many of these operations. The aim of this report is to assess the long-term outcomes of femoral cannulations in patients who underwent minimally invasive procedures. One hundred and sixty patients underwent operations by the port-access method between January 2002 and October 2006. Cardiopulmonary bypass was established by femoral artery vein cannulation, and a transthoracic clamp was used for the aortic occlusion. One hundred and twenty-one patients were under follow-up in the outpatient clinic and 85 patients underwent Doppler ultrasonography (US) for femoral arterial and venous stenosis. The mean follow-up was 27.9 months (range 1-57 months). There were three hospital mortalities (1.86%), and five late mortalities in this series. The mean follow-up for the Doppler examination was 20.54 months (range 1 56 months). There were two seromas and three wound complications (2.48%), all of which healed after outpatient treatment. All of the flow patterns of the common femoral arteries (CFA) were triphasic except in three of the patients. Three patients (2.48%) were found to have arterial stenosis. One patient with intermittant claudication underwent percutaneous dilatation and stenting of the CFA. Doppler US detected luminal narrowing in two patients who had been having no symptoms, and they are being followed in the outpatient clinic without any complaints. We found a chronic recanalized thrombotic change in the common femoral vein (CFV) in one patient (0.63%). Our study demonstrates vessel patency and/or stenosis in patients without complaints. In conclusion, femoral artery and vein cannulation for port-access surgery with transthoracic clamping can be performed successfully with excellent results in the mid-term. PMID- 17846078 TI - Is thrombolysis or surgery the best option for acute prosthetic valve thrombosis? AB - A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether the optimal treatment strategy for acute prosthetic valve thrombosis (PVT) is surgical management or thrombolytic therapy. Using the reported search 96 papers were identified. Twelve papers represented the best evidence on the subject, and the author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study comments and weaknesses were tabulated for these. Recent AHA/ACC guidelines were also included, as were two large case series of surgical management for comparison. We conclude that the management of obstructive PVT remains widely debated due to a lack of randomised controlled trials. Surgery has been the traditional management of choice, but thrombolysis has recently been proposed as a first-line therapy. Both surgery and thrombolysis can be used with high rates of success and relatively low complication rates, though NYHA class at presentation has a significant bearing on surgical mortality and thrombus size affects complication rates with thrombolysis. Thrombolysis appears particularly favoured when the thrombus area as assessed by transoesophageal echocardiography is small (<0.8 cm(2)), as high success rates and low complication rates have been reported, and thrombolysis does not preclude the patient from proceeding to surgery if it fails. Presentation in a high NYHA class of heart failure or cardiogenic shock is the most difficult patient to decide between surgery and thrombolysis. Surgery for these patients may remain the mainstay of treatment unless the clot burden is particularly small or the patient's co-morbidities make surgery unacceptably high-risk. PMID- 17846079 TI - Unmasking different mechanical and energetic roles for the small heat shock proteins CryAB and HSPB2 using genetically modified mouse hearts. AB - CryAB and HSPB2 are small heat shock proteins constitutively expressed in the heart. CryAB protects cytoskeletal organization and intermediate filament assembly; the functions of HSPB2 are unknown. The promoters of CryAB and HSPB2 share regulatory elements, making identifying their separate functions difficult. Here, using a genetic approach, we report distinct roles for these sHSPs, with CryAB protecting mechanical properties and HSPB2 protecting energy reserve. Isolated hearts of wild type mice (WT), mice lacking both sHSPs (DKO), WT mice overexpressing mouse CryAB protein (mCryAB(Tg)), and mice with no HSPB2 made by crossing DKO with mCryAB(Tg) (DKO/mCryAB(Tg)) were stressed with either ischemia/reperfusion or inotropic stimulation. Contractile performance and energetics were measured using 31P NMR spectroscopy. Ischemia/reperfusion caused severe diastolic dysfunction in DKO hearts. Recovery of [ATP] and [PCr] during reperfusion was impaired only in DKO/mCryAB(Tg). During inotropic stimulation, DKO/mCryAB(Tg) showed blunted systolic and diastolic function and revealed massive energy wasting on acute stress: |deltaG(-ATP)| decreased in DKO by 6.4 +/ 0.7 and in DKO/mCryAB(Tg) by 5.5 +/- 0.8 kJ/mol compared with only approximately 3.3 kJ/mol in WT and mCryAB(Tg). Thus, CryAB and HSPB2 proteins play nonredundant roles in the heart, CryAB in structural remodeling and HSPB2 in maintaining energetic balance. PMID- 17846080 TI - Constitutive nuclear import of latent and activated STAT5a by its coiled coil domain. AB - Signal transducer and activator of transcription 5a (STAT5a) is a critical transcription factor for a number of physiological processes including hematopoiesis and mammary gland development. Cytokines such as growth hormone, prolactin, erythropoietin, and interleukin-2 stimulate the activation of STAT5a by tyrosine phosphorylation. Tyrosine phosphorylation confers a conformational change and the ability to bind specific target DNA. To execute its function as a signaling molecule and transcription factor, accurate cellular localization of STAT5a is essential. This study explores the nuclear trafficking of STAT5a both before phosphorylation and after tyrosine phosphorylation. With the use of live cell imaging we demonstrate the continuous shuttling of STAT5a in and out of the nucleus. Evaluation of a series of mutations and deletions identifies a region within the coiled coil domain of STAT5a that is critical for nuclear import of both unphosphorylated and tyrosine-phosphorylated forms. The mechanism that regulates transport of STAT5a through nuclear pore complexes into the nucleus is therefore independent of tyrosine phosphorylation. However, after tyrosine phosphorylation, STAT5a accumulates in the nucleus because of its retention by DNA binding. These findings should provide a foundation for further studies that involve targeting the activity of STAT5a. PMID- 17846082 TI - Estrogen and the inner ear: megalin knockout mice suffer progressive hearing loss. AB - Megalin, the largest member of the low-density lipoprotein receptor-related protein family, functions as an endocytic receptor for a variety of essential lipophilic metabolites, including the steroid hormone estrogen. In the cochlea, megalin is strongly expressed within the marginal cells of the stria vascularis, and previous studies demonstrated that beta-estrogen receptors are also expressed in megalin-expressing marginal cells. In the present study, we demonstrate that homozygous megalin mutant mice exhibit profound hearing loss at 3 months of age associated with features of presbycusis, enrichment of lipofuscin granules, and a reduced number of microvilli in marginal cells of the stria vascularis. FITC labeled beta-estrogen is taken up into the strial marginal cells; however, in megalin-deficient mice the uptake of FITC-labeled beta-estrogen is reduced. This highlights beta-estrogen as a possible carrier-bound candidate ligand for megalin and supports the concept that estrogen may function via megalin within the inner ear. A crucial role of megalin in hearing should be considered and the megalin/estrogen interaction needs to be discussed in the context of early presbycusis in estrogen-deficient humans and mice. PMID- 17846081 TI - The serotonin 5-HT2B receptor controls bone mass via osteoblast recruitment and proliferation. AB - The monoamine serotonin (5-HT), a well-known neurotransmitter, is also important in peripheral tissues. Several studies have suggested that 5-HT is involved in bone metabolism. Starting from our original observation of increased 5-HT(2B) receptor (5-HT(2B)R) expression during in vitro osteoblast differentiation, we investigated a putative bone phenotype in vivo in 5-HT(2B)R knockout mice. Of interest, 5-HT(2B)R mutant female mice displayed reduced bone density that was significant from age 4 months and had intensified by 12 and 18 months. This histomorphometrically confirmed osteopenia seems to be due to reduced bone formation because 1) the alkaline phosphatase-positive colony-forming unit capacity of bone marrow precursors was markedly reduced in the 5-HT(2B)R mutant mice from 4 to 12 months of age, 2) ex vivo primary osteoblasts from mutant mice exhibited reduced proliferation and delayed differentiation, and 3) calcium incorporation was markedly reduced in osteoblasts after 5-HT(2B)R depletion (produced genetically or by pharmacological inactivation). These findings support the hypothesis that the 5-HT(2B)R receptor facilitates osteoblast recruitment and proliferation and that its absence leads to osteopenia that worsens with age. We show here, for the first time, that the 5-HT(2B)R receptor is a physiological mediator of 5-HT in bone formation and, potentially, in the onset of osteoporosis in aging women. PMID- 17846083 TI - Calpain counteracts mechanosensitive apoptosis of vascular smooth muscle cells in vitro and in vivo. AB - Mechanical forces contribute to vascular remodeling processes. Elevated mechanical stress causes apoptosis of vascular smooth muscle cells (VSMCs) within the media. This study examined the role of the cystein protease calpain in force induced vascular cell apoptosis and its effect on injury-induced vascular remodeling processes. VSMCs were exposed to cyclic tensile force in vitro, which resulted in increased p53 protein expression and transcriptional activity as well as a significant increase of apoptotic VSMCs. Apoptosis was prevented by the p53 inhibitor pifithrin and by p53 antisense oligonucleotides, indicating dependency of force-induced apoptosis on p53. Simultaneously, calpain activity increased by mechanical stress. Prevention of calpain activation by calpeptin or antisense oligonucleotides augmented strain-induced p53 expression and transcriptional activity, resulting in a further increase of apoptotic rate. p53 protein was directly disintegrated by activated calpain. The in vivo relevance of the findings was tested: pharmacologic inhibition of initial calpain activation augmented early apoptosis of medial VSMCs 24 h after balloon injury in a p53 dependent manner but resulted in a marked increase in late neointima formation. We conclude that calpain counteracts mechanically induced excessive VSMC apoptosis through its p53-degrading properties, which identifies calpain as a key regulator of mechanosensitive remodeling processes of the vascular wall. PMID- 17846084 TI - Humpty-Dumpty Syndrome. PMID- 17846085 TI - Facts and indicators on palliative care development in 52 countries of the WHO European region: results of an EAPC Task Force. AB - The European Association for Palliative Care Task (EAPC) Force on the Development of Palliative Care in Europe was created in 2003 and the results of its work are now being reported in full, both here and in several other publications. The objective of the Task Force is to assess the degree of palliative care development in the European Region as defined by the World Health Organization (WHO). The Task Force is a collaboration between EAPC, the International Observatory on End of Life Care, Help the Hospices and the International Association for Hospice and Palliative Care. The University of Navarra have collaborated in the dissemination of results and is involved in further developments of this group. Four studies, each with different working methods, made up the study protocol: a literature review, a review of all the existing palliative care directories in Europe, a qualitative ;Eurobarometer' survey and a quantitative ;Facts Questionnaire' survey. The work of the Task Force covers the entire WHO European Region of 52 countries. In this article we present a comparative study on the development of palliative care in Europe, drawing on all four elements of the study. Different models of service delivery have been developed and implemented throughout the countries of Europe. For example, in addition to the UK, the countries of Germany, Austria, Poland and Italy have a well-developed and extensive network of hospices. The model for mobile teams or hospital support teams has been adopted in a number of countries, most notably in France. Day Centres are a development that is characteristic of the UK with hundreds of these services currently in operation. The number of beds per million inhabitants ranges between 45-75 beds in the most advanced European countries, to only a few beds in others. Estimates on the number of physicians working full time in palliative care are shown. The countries with the highest development of palliative care in their respective subregions as measured in terms of ratio of services per one million inhabitants are: Western Europe - UK (15); Central and Eastern Europe - Poland (9); Commonwealth of Independent States - Armenia (8). This paper also presents indicators on the development of palliative care based on the bibliometric analysis of scientific journals and on the vitality of the palliative care movement in each country. PMID- 17846086 TI - The use of long-term low-molecular weight heparin for the treatment of venous thromboembolism in palliative care patients with advanced cancer: a case series of sixty two patients. AB - The advantages of low-molecular weight heparin (LMWH) over warfarin, in the treatment of cancer associated venous thromboembolism (VTE) are well reported. However the studies supporting LMWH include few patients representative of the palliative care population. Although LMWH has advantages over warfarin it is still unclear, within the palliative care environment, how long anticoagulation should be continued, what dose of LMWH should be used and whether palliative care patients experience different complication rates such as bleeding, heparin induced thrombocytopenia and osteoporosis. We report a case series of 62 patients with advanced malignancy and VTE treated with long-term LMWH according to either the CLOT (full dose) or Montreal (reduced dose) regime. Seventy-four percent of patients self-administered LMWH, whereas 24% had it given by a carer and 2% by the district nurse. LMWH was given for median duration of 97 days; the most common reason for discontinuation of therapy being admission to die or commencement of the care pathway (n = 50, 81%). A further 11% (n = 7) stopped after 6 months of treatment. Of these 3 (43%) developed clinical symptomatic recurrence of VTE. The overall minor bleeding rate was 8.1% (95% confidence interval 3.5-17.5%), and this was not associated with NSAID or steroid use. No major bleeding events were observed. No patients developed evidence of heparin induced thrombocytopenia or osteoporosis.Long-term LMWH appears effective in treatment of VTE in the palliative care population with advanced cancer. A randomised control trial is required to identify the best dose required to ensure optimum efficacy and safety. PMID- 17846087 TI - How can occupational therapists measure outcomes in palliative care? AB - The objective of this paper is to identify an outcome measure for occupational therapy interventions with palliative clients, in particular Home Assessments. Several possibilities beyond traditional functional measures are considered, and the notion of quality of life (QoL) as a potential measure and routine part of assessment is discussed.A systematic literature search resulted in 45 QoL tools that might be suitable for palliative care. The validation or development papers for these tools were closely examined. Twenty-four instruments met the inclusion criteria for further consideration for use by occupational therapists. The research found that it may be feasible for occupational therapists to use a QoL tool as a routine part of assessing each palliative patient, with the objective of focusing interventions to priority areas identified by the patient. Further work in this area will identify a range of established and validated methods of assessing QoL, suitable for different stages within the palliative phase of illness for purposes including assessment, support and targeted interventions. PMID- 17846088 TI - What determines referral of UK patients with haematological malignancies to palliative care services? An exploratory study using hospital records. AB - We investigated the frequency and characteristics of patients with haematological malignancies (HMs) who were, or were not, referred for specialist palliative care (SPC). Data were abstracted from hospital records of 108 patients who died - 27 with leukaemia, 11 with myelodysplastic syndromes, 48 with lymphoma and 22 with myeloma. Ninety-three patients (86.1%) were >60 years of age at diagnosis, with 33 (30.6%) being >or=80 years and 31 (28.7%) having existing comorbidities. Thirty-three patients (30.6%) were referred to SPC services. There was little difference by age or HM diagnosis in referred patients. Seventeen of 67 patients (25.4%) dying on a hospital ward received SPC compared with 6/7 (85.7%) dying at home. Time between diagnosis and death influenced the referral - 24/52 patients (46.2%) dying >or=30 days after diagnosis received SPC compared with 8/42 (19.1%) dying within 30 days. In 14 patients, HM diagnosis was confirmed after death. Identification of these 14 patients is likely to be a unique feature of our study, as patients were selected from a regional, population-based register with centralized diagnostic services, enabling the identification of all patients with HM. The interface between curative and palliative treatment in HM is more complex than the National Institute for Clinical Excellence recommendations suggest. PMID- 17846089 TI - Palliative care provision for people with intellectual disabilities: interviews with specialist palliative care professionals in London. AB - Growing numbers of people with intellectual disabilities (ID) are in need of palliative care, but there is inequity of access to palliative care services for this group. This study investigates the issues and difficulties arising for palliative care staff in providing care for people with ID. Semi-structured interviews were conducted with 32 palliative care professionals in London. Factors affecting palliative care provision for people with ID included social issues (home situation and family issues), emotional and cognitive issues (fear, patient understanding, communication, cooperation and capacity to consent), problems with assessment, and the impact on staff and other patients. An underlying theme was the need to take more time and to build trust. Despite the challenges, many palliative care staff managed the care of people with ID well. The importance of collaboration with carers and ID services is highlighted. Further studies are needed to investigate how widespread the problems are. PMID- 17846090 TI - A randomized, controlled trial of physician postures when breaking bad news to cancer patients. AB - Medical training teaches physicians to sit when breaking bad news, though there have been no controlled studies to support this advice. We aimed to establish cancer patients' preference for physician posture when physicians break bad news using a randomized controlled crossover trial in a department of palliative care at a large US cancer center. Referred patients were blind to the hypothesis and watched video sequences of a sitting or standing physician breaking bad news to a cancer patient and 168 of 173 participants (88 female) completed the study. Sitting physicians were preferred and viewed as significantly more compassionate than standing physicians (P < 0.0001) but other physician attributes and behaviours were generally rated as of equal or more importance than posture. In summary, cancer patients, especially females, prefer physicians to sit when breaking bad news and rate physicians who adopt this posture as more compassionate. However, sitting posture alone is unlikely to compensate for poor communication skills and lack of other respectful gestures during a consultation. PMID- 17846091 TI - Truth-telling in discussing prognosis in advanced life-limiting illnesses: a systematic review. AB - Many health professionals (HPs) express discomfort at having to broach the topic of prognosis, including limited life expectancy, and may withhold information or not disclose prognosis. A systematic review was conducted of 46 studies relating to truth-telling in discussing prognosis with patients with progressive, advanced life-limiting illnesses and their caregivers. Relevant studies meeting the inclusion criteria were identified by searching computerized databases (MEDLINE, EMBASE, CINAHL, PsychINFO and Cochrane Register of Controlled Trials) up to November 2004, with handsearching of studies, as well as inclusion of studies satisfying selection criteria reported in 2005 by the authors. The reference lists of identified studies were hand-searched for further relevant studies. Inclusion criteria were studies of any design evaluating communication of prognostic information that included adult patients with an advanced, life limiting illness; their caregivers; and qualified HPs. Results showed that although the majority of HPs believed that patients and caregivers should be told the truth about the prognosis, in practice, many either avoid discussing the topic or withhold information. Reasons include perceived lack of training, stress, no time to attend to the patient's emotional needs, fear of a negative impact on the patient, uncertainty about prognostication, requests from family members to withhold information and a feeling of inadequacy or hopelessness regarding the unavailability of further curative treatment. Studies suggest that patients can discuss the topic without it having a negative impact on them. Differences and similarities in findings from different cultures are explored. PMID- 17846093 TI - Community palliative care development: evaluating the role and impact of a general practitioner with a special interest in palliative medicine. AB - In the context of an increased national policy focus on the development of palliative and end of life care services the post of a GP with a special interest in palliative medicine (GPSI) was introduced in one region of the UK to fortify its current palliative care provision. This paper presents findings from an evaluation of the first 2 years of the GPSI post. A mixed method evaluation design was adopted incorporating qualitative interviews, a satisfaction survey and an activity log. As a concept, the GPSI was welcomed as a suitable and imaginative way to provide much needed medical input. At baseline interviews stakeholders saw the role as an added resource both clinically and educationally, placing highest value on the clinical element of the role. There were concerns related to referral practices (referral was via a GP only) as well as the low profile of the new role. At the final stage of the evaluation, almost 2 years since the role began, stakeholders noted that the use of the GPSI for informal advice and support was highly valued, but also noted that more had been expected, particularly in relation to increased clinical input. The evaluation contained important lessons both for the continuation of this GPSI post and for other regions considering appointing a GPSI in this speciality. PMID- 17846092 TI - An evidence base for a palliative care chaplaincy service in Northern Ireland. AB - Palliative care encompasses spiritual as well as physical, social and psychological aspects. Spiritual care has been identified as a key concern of dying patients. During an audit of the Northern Ireland Hospice chaplaincy service against the national Standards for Hospice and Palliative Care Chaplaincy (2003), 62 patients' spiritual needs along with their interactions with the hospice chaplains were assessed by using a questionnaire survey and reviewing data recorded on their pastoral care notes. Findings suggest that the Standards were useful for assessing and addressing spiritual needs. Access to the chaplaincy service (Standard 1) was partially met and Standard 2's spiritual criteria were fully met. The participants, of whom 92% had a faith in God or a Higher Being, highlighted their top six spiritual needs as: to have the time to think; to have hope; to deal with unresolved issues; to prepare for death; to express true feelings without being judged; to speak of important relationships. The majority of the participants (82%) felt their spiritual needs had been addressed and viewed their interaction with the chaplaincy service positively. Recommendations were made relating to improve communication of chaplaincy services. PMID- 17846094 TI - Taking care of terminally-ill patients at home - the economic perspective revisited. AB - End-of-life care can be delivered in a variety of settings, whereby the majority of terminally-ill cancer patients prefer to die at home. The aim of our study is to evaluate health services utilisation during the last year of life, and to compare terminally ill patients who have received home-specialised palliative care services (HSPCS) with patients who died receiving home non-specialised palliative care services. The study included 120 and 515 patients, respectively, who died between 1999-2000. Age and gender distribution were similar in both groups. During the last year of life, mean health services cost per person among the HSPCS group was lower by more then 30% (P < 0.005). The median cost per patient was as low as one-fifth in the last month. Men and the older age group of 65 and above, cost significantly less compared with women and younger patients, respectively, regardless of provider setting. The main differences in health services utilisation were in hospitalisations and oncology treatments (P < 0.01 and P < 0.05, respectively). PMID- 17846095 TI - Cervical intrathecal analgesia for head and neck/upper limb cancer pain: six case reports. AB - We describe six cases of head and neck or upper limb cancer palliative care patients with refractory pain, treated with an intrathecal catheter placed at cervical or upper thoracic spinal levels with a non-implanted, externalized and tunnelled delivery system. In these cases, this system was safe and effective. PMID- 17846096 TI - The use of herbal and other dietary supplements and the potential for drug interactions in palliative care. PMID- 17846098 TI - Olfactory conditioning of positive performance in humans. AB - Olfactory conditioning effects have been widely demonstrated in the animal literature but more seldom in human populations and rarely of consciously controlled human behaviors. Building upon previous work on negative performance, we report the first experimental evidence that odors can be used effectively in a classical conditioning paradigm to positively influence human behavior. In the present study, underachieving schoolchildren experienced unexpected success at a paper-and-pencil task in the presence of an ambient odor. When they later experienced the same odor again, performance on other tasks was superior to that of relevant control groups. These data substantially extend previous results on human olfactory classical conditioning and show that odors potentially can be used to exert positive influences on human behavior. PMID- 17846099 TI - Riboflavin-binding protein is a novel bitter inhibitor. AB - Riboflavin-binding protein (RBP) from chicken egg, which was recently reported to be a selective sweet inhibitor for protein sweeteners, was also found to be a bitter inhibitor. RBP elicited broadly tuned inhibition of various bitter substances including quinine-HCl, naringin, theobromine, caffeine, glycyl-L phenylalanine (Gly-Phe), and denatonium benzoate, whereas several other proteins, such as ovalbumin (OVA) and beta-lactoglobulin, were ineffective in reducing bitterness of these same compounds. Both the bitter tastes of quinine and caffeine were reduced following an oral prerinse with RBP. It was found that RBP binds to quinine but not to caffeine, theobromine, naringin, and Gly-Phe. However, the binding of RBP to quinine was probably not responsible for the bitter inhibition because OVA bound to quinine as well as RBP. Based on these results, it is suggested that the bitter inhibitory effect of RBP is the consequence of its ability to interact with taste receptors rather than because it interacts with the bitter tastants themselves. RBP may have practical uses in reducing bitterness of foods and pharmaceuticals. It may also prove a useful tool in studies of mechanisms of bitter taste. PMID- 17846100 TI - Methyl salicylate, identified as primary odorant of a specific receptor neuron type, inhibits oviposition by the moth Mamestra brassicae L. (Lepidoptera, noctuidae). AB - The cabbage moth, Mamestra brassicae L. (Lepidoptera, Noctuidae), is a polyphagous species that is often choosing plants of Brassica as hosts for oviposition. In the search for biologically relevant odorants used by these moths, gas chromatography linked to electrophysiological recordings from single receptor neurons (RNs) has been employed, resulting in classification of distinct types of neurons. This study presents specific olfactory RNs responding to methyl salicylate (MeS) as primary odorant and showing a weak response to methyl benzoate, the 2 aromatic compounds occurring together in several plant species. In 2 cases, the neuron was colocated with another RN type responding to 6 green leaf volatiles: 1-hexanol, (3Z)-hexen-1-ol, (2E)-hexen-1-ol, (3Z)-hexenyl acetate, (2Z)-hexen-1-ol, and an unidentified compound. Whereas the specific RNs detected the minor amounts of MeS in some plants, the compound was not found by gas chromatography linked to mass spectrometry in intact plants, but it was found after herbivore attack. The behavioral effect of MeS was studied in outdoor test arenas with Brassica napus and artificial plants. These experiments indicated that mated M. brassicae females avoid plants with dispensers emitting MeS. As it is induced by caterpillar feeding, this compound may mediate a message to mated M. brassicae females that the plant is already occupied. PMID- 17846101 TI - Problem-solving therapy for late-life depression in home care: a randomized field trial. AB - OBJECTIVE: The authors present data from a pilot research program initiated to develop, refine, and test the outcomes of Brief Problem-Solving Therapy in Home Care (PST-HC) that targets the needs of older adults identified with severe depressive symptoms in an acute home care setting. METHODS: A pilot randomized clinical trial compared the impact of PST-HC to usual care (UC) in a sample of older medically ill home care patients identified with severe depressive symptoms. Forty patients were randomly assigned to either six weekly sessions of PST-HC in their home or standard home care services. Depression, quality of life, and problem-solving ability were measured at baseline, posttreatment, three-month follow-up, and six-month follow-up by blinded evaluators. RESULTS: All 40 patients provided follow-up data. No differences between the two groups were found on any demographic variables. Outcome data suggested significant improvements in depression scores over time after PST-HC, relative to UC. PST-HC patients reported higher quality of life and problem-solving ability scores relative to UC. CONCLUSION: Results suggest that PST-HC is well tolerated and holds promise for reducing persistent depressive symptoms. The authors discuss limitations in terms of the "real-world" applicability of this psychosocial treatment for late-life depression. PMID- 17846102 TI - A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia. AB - OBJECTIVE: To compare citalopram and risperidone for the treatment of psychotic symptoms and agitation associated with dementia, with a priori hypotheses that risperidone would be more efficacious for psychosis and citalopram for agitation. METHODS: A 12-week randomized, controlled trial in nondepressed patients with dementia hospitalized because of behavioral symptoms (N = 103) was conducted at the University of Pittsburgh Medical Center. Participants were consecutively recruited on an inpatient unit if they had at least one moderate to severe target symptom (aggression, agitation, hostility, suspiciousness, hallucinations, or delusions). Once they improved sufficiently, they were discharged to nursing homes, personal care homes, or residential homes for continued treatment. Planned pre-post and mixed model analyses of the main outcome measures of Neurobehavioral Rating Scale and Side Effect Rating Scale at baseline and at weekly/biweekly intervals were conducted. RESULTS: Completion rates did not differ for citalopram and risperidone (overall completion rate: 44%). Agitation symptoms (aggression, agitation, or hostility) and psychotic symptoms (suspiciousness, hallucinations, or delusions) decreased in both treatment groups but the improvement did not differ significantly between the two groups. There was a significant increase in side effect burden with risperidone but not with citalopram such that the two groups differed significantly. CONCLUSION: No statistical difference was found in the efficacy of citalopram and risperidone for the treatment of either agitation or psychotic symptoms in patients with dementia. These findings need to be replicated before citalopram or other serotonergic antidepressants can be recommended as alternatives to antipsychotics for the treatment of agitation or psychotic symptoms associated with dementia. PMID- 17846103 TI - The role of cis-regulatory motifs and genetical control of expression in the divergence of yeast duplicate genes. AB - Expression divergence of duplicate genes is widely believed to be important for their retention and evolution of new function, although the mechanism that determines their expression divergence remains unclear. We use a genetical genomics approach to explore divergence in genetical control of yeast duplicate genes created by a whole-genome duplication that occurred about 100 MYA and those with a younger duplication age. The analysis reveals that duplicate genes have a significantly higher probability of sharing common genetic control than pairs of singleton genes. The expression quantitative trait loci (eQTLs) have diverged completely for a high proportion of duplicate pairs, whereas a substantially larger proportion of duplicates share common regulatory motifs after 100 Myr of divergent evolution. The similarity in both genetical control and cis motif structure for a duplicate pair is a reflection of its evolutionary age. This study reveals that up to 20% of variation in expression between ancient duplicate gene pairs in the yeast genome can be explained by both cis motif divergence (approximately 8%) and by trans eQTL divergence (approximately 10%). Initially, divergence in all 3 aspects of cis motif structure, trans-genetical control, and expression evolves coordinately with the coding sequence divergence of both young and old duplicate pairs. These findings highlight the importance of divergence in both cis motif structure and trans-genetical control in the diverse set of mechanisms underlying the expression divergence of yeast duplicate genes. PMID- 17846104 TI - Patterns of Y-chromosome diversity intersect with the Trans-New Guinea hypothesis. AB - The island of New Guinea received part of the first human expansion out of Africa (>40,000 years ago), but its human genetic history remains poorly understood. In this study, we examined Y-chromosome diversity in 162 samples from the Bird's Head region of northwest New Guinea (NWNG) and compared the results with previously obtained data from other parts of the island. NWNG harbors a high level of cultural and linguistic diversity and is inhabited by non-Austronesian (i.e., Papuan)-speaking groups as well as harboring most of West New Guinea's (WNG) Austronesian-speaking groups. However, 97.5% of its Y-chromosomes belong to 5 haplogroups that originated in Melanesia; hence, the Y-chromosome diversity of NWNG (and, according to available data, of New Guinea as a whole) essentially reflects a local history. The remaining 2.5% belong to 2 haplogroups (O-M119 and O-M122) of East Asian origin, which were brought to New Guinea by Austronesian speaking migrants around 3,500 years ago. Thus, the Austronesian expansion had only a small impact on shaping Y-chromosome diversity in NWNG, although the linguistic impact of this expansion to this region was much higher. In contrast, the expansion of Trans-New Guinea (TNG) speakers (non-Austronesian) starting about 6,000-10,000 years ago from the central highlands of what is now Papua New Guinea, presumably in combination with the expansion of agriculture, played a more important role in determining the Y-chromosome diversity of New Guinea. In particular, we identified 2 haplogroups (M-P34 and K-M254) as suggestive markers for the TNG expansion, whereas 2 other haplogroups (C-M38 and K-M9) most likely reflect the earlier local Y-chromosome diversity. We propose that sex-biased differences in the social structure and cultural heritage of the people involved in the Austronesian and the TNG expansions played an important role (among other factors) in shaping the New Guinean Y-chromosome landscape. PMID- 17846105 TI - Human oocyte cryopreservation. AB - The clinical role of oocyte cryopreservation in assisted reproduction, as an adjunct to sperm and embryo cryopreservation, has been comparatively slow to evolve as a consequence of theoretical concerns related to efficacy and safety. Basic biological studies in the 1990's alleviated many of these concerns leading to more widespread adoption of the technology. While a number of babies were born from the approach validated in the 1990's, its perceived clinical inefficiency led to the search for improved methods. Introduction of elevated dehydrating sucrose concentrations during cryopreservation increased survival and fertilization rates, but there is no well-controlled evidence of improved clinical outcome. Similarly, the use of sodium-depleted cryopreservation media has not been demonstrated to increase clinical efficiency. More recently, and in the absence of basic biological studies addressing safety issues, the application of vitrification techniques to human oocytes has resulted in reports of a number of live births. The small number of babies born from clinical oocyte cryopreservation and the paucity of well-controlled studies currently preclude valid comparisons between approaches. Legal restrictions on the ability to select embryos from cryopreserved oocytes in Italy, where many of the available reports originate, also obscure attempts to assess oocyte cryopreservation objectively. PMID- 17846106 TI - Targeted drug delivery to enhance efficacy and shorten treatment duration in disseminated Mycobacterium avium infection in mice. AB - OBJECTIVES: Improvement of the efficacy of drug treatment in mycobacterial infection by the development and application of targeted drug delivery. METHODS: In disseminated Mycobacterium avium infection in mice, the relative efficacy of the antimycobacterial agents that are currently used in combination therapy was investigated. Next, the effect of the addition of targeted delivery of amikacin to the infected tissues in the initial phase of treatment was studied. Amikacin was chosen because of its unique rapid and high mycobacterial killing capacity. As drug delivery tool, long-circulating sterically stabilized liposomes were used. RESULTS: Treatment with clarithromycin alone daily (6 days a week) slowly killed most of the mycobacteria in the lung, liver, spleen, inguinal and mesenterial lymph nodes. However, after 24 weeks of treatment, persistence of substantial numbers of mycobacteria in the infected organs was observed. The addition of ethambutol to the clarithromycin regimen did not significantly enhance the efficacy of treatment, neither did rifampicin as a third agent. In contrast, the addition of liposomal amikacin in the initial phase of therapy resulted in rapid and complete elimination of the mycobacteria in all infected organs within 12 weeks of treatment without relapse of infection. As a result, total treatment duration could be significantly reduced to 12 weeks. CONCLUSIONS: In M. avium infection in mice, the approach of targeted drug delivery was successful. The rapid decrease in the mycobacterial load followed by complete killing, including the persistent mycobacteria considered responsible for relapse of infection, allows a significant reduction of the total treatment duration. PMID- 17846107 TI - Acute necrotizing encephalopathy: a relapsing case in a European adult. PMID- 17846108 TI - Coiling of basilar tip aneurysms: results in 154 consecutive patients with emphasis on recurrent haemorrhage and re-treatment during mid- and long-term follow-up. AB - PURPOSE: The purpose of this study is to report mid- and long-term clinical and angiographic results of coiling of basilar tip aneurysms. MATERIALS AND METHODS: Between January 1995 and August 2006, 154 basilar tip aneurysms were coiled. A total of 114 (74%) had ruptured and 40 (26%) were unruptured. There were 42 men and 112 women taking part in this study, with a mean age of 50.5 years (median, 50; range, 25-73 years). The mean aneurysm size was 11.1 mm (median, 10; range, 2 30 mm) and 71 (46%) were large or giant. Of 154 aneurysms, 40 (26%) were primarily coiled with a supporting device. RESULTS: Initial occlusion was (near) complete in 144 (94%) and incomplete in 10 (6%) aneurysms. The combined procedural mortality and morbidity was 3.8% (6 of 154, 95% CI 1.4-8.3%). The mean clinical follow-up of 144 surviving patients was 53 months (range, 3-144 months; 637 patient-years). The annual incidence rate for recurrent haemorrhage was 0.3% (2 in 637 patient years, 95% CI 0.04-1.1%). During angiographic follow-up of mean 34 months (range, 6-122 months) in 138 patients (96%), 27 basilar tip aneurysms (17.5%) re-opened over time and were additionally coiled. Of these, 11 repeatedly re-opened and were repeatedly coiled. An aneurysm size of median >10 mm was the only significant predictor for re-treatment at follow-up (OR 7.0, 95% CI 2.5 19.7). CONCLUSION: Coiling of basilar tip aneurysms is safe and effective in preventing recurrent haemorrhage. Follow-up angiography is mandatory to timely detection of re-opening, especially in large and giant aneurysms. PMID- 17846109 TI - Hippocampal activation in adults with mild cognitive impairment predicts subsequent cognitive decline. AB - OBJECTIVE: To use functional MRI (fMRI) to investigate whether hippocampal activation during a memory task can predict cognitive decline in individuals with mild cognitive impairment (MCI). METHODS: 25 older individuals with MCI performed a visual scene encoding task during fMRI scanning, and were followed clinically for at least 4 years after scanning. A hypothesis driven analysis of fMRI data was performed. First, fMRI data were analysed at the group level to identify the regions of the hippocampal formation that were engaged by this memory task. Parameter estimates of each subject's memory related hippocampal activation (% signal change) were extracted and were analysed with a linear regression model to determine whether hippocampal activation predicted the degree or rate of cognitive decline, as measured by change in Clinical Dementia Rating Sum-of-Boxes (CDR-SB). RESULTS: Over 5.9 (1.2) years of follow-up after scanning, subjects varied widely in degree and rate of cognitive decline (change in CDR-SB ranged from 0 to 6, and the rate ranged from 0 to 1 CDR-SB unit/year). Greater hippocampal activation predicted greater degree and rate of subsequent cognitive decline (p<0.05). This finding was present even after controlling for baseline degree of impairment (CDR-SB), age, education and hippocampal volume, as well as gender and apolipoprotein E status. In addition, an exploratory whole brain analysis produced convergent results, demonstrating that the hippocampal formation was the only brain region where activation predicted cognitive decline. CONCLUSIONS: In individuals with MCI, greater memory task related hippocampal activation is predictive of a greater degree and rate of cognitive decline subsequent to scanning. fMRI may provide a physiological imaging biomarker useful for identifying the subgroup of MCI individuals at highest risk of cognitive decline for potential inclusion in disease modifying clinical trials. PMID- 17846110 TI - Mitoxantrone as induction treatment in aggressive relapsing remitting multiple sclerosis: treatment response factors in a 5 year follow-up observational study of 100 consecutive patients. AB - BACKGROUND: Mitoxantrone was approved by the French health authority (AFSAPPS) in October 2003 to treat patients with aggressive multiple sclerosis (MS). OBJECTIVE: To report the long term effectiveness and safety of mitoxantrone as induction therapy in patients with aggressive relapsing-remitting MS, and to assess treatment response factors. MATERIAL AND METHODS: 100 consecutive patients with aggressive relapsing-remitting MS received mitoxantrone 20 mg monthly combined with methylprednisolone 1 g for 6 months. Relapses, Expanded Disability Status Scale (EDSS) and drug safety were assessed every 6 months for up to at least 5 years. Within 6 months after induction, 73 patients received maintenance therapy (mitoxantrone every 3 months (n = 21); interferon beta (n = 25); azathioprine (n = 15); methotrexate (n = 7); glatiramer acetate (n = 5)). RESULTS: During the 12 months following initiation of mitoxantrone, the annual relapse rate (ARR) was reduced by 91%, 78% of patients remained relapse free, MRI activity was reduced by 89%, the mean EDSS decreased by 1.2 points (p<10(-6)) and 64% of patients improved by 1 point or more on the EDSS. In the longer term, the ARR reduction was sustained (0.29-0.42 for up to 5 years), the median time to the first relapse was 2.8 years and disability remained improved after 5 years. Younger age and lower EDSS score at the start of mitoxantrone treatment were predictive of better treatment response. Three patients presented with an asymptomatic decrease in left ventricular ejection fraction to less than 50% (one reversible). One patient was diagnosed with acute myeloid leukaemia (remission 5 years after diagnosis). CONCLUSION: Mitoxantrone monthly for 6 months as induction therapy followed by maintenance treatment showed sustained clinical benefit for up to 5 years with an acceptable adverse events profile in patients with aggressive relapsing-remitting MS. PMID- 17846111 TI - Microembolic signals at 48 hours after stroke onset contribute to new ischaemia within a week. AB - BACKGROUND AND AIMS: We investigated whether new ischaemic lesions (NIL) on follow-up diffusion weighted magnetic resonance imaging (DWI) are associated with microembolic signals (MES) within 24 h or at 48 h after stroke onset. METHODS: Patients had acute ischaemic stroke and were studied within 24 h of onset. Transcranial Doppler ultrasonography (TCD) was prospectively examined twice, within 24 h and at 48 h after onset. DWI was conducted twice, on admission and on day 7. NIL were defined as the presence of hyperintense lesions undetected on initial DWI. RESULTS: 125 patients were consecutively enrolled from November 2004 to March 2006. TCD detected MES in 49% within 24 h and in 29% at 48 h after onset. In 27 patients with small vessel disease, MES were found in 8 (30%) patients within 24 h and in 5 (19%) patients at 48 h after stroke onset. In contrast, in 20 patients with large vessel disease, 11 (55%) patients within 24 h and 7 (35%) at 48 h had MES. Follow-up DWI detected NIL in 28 of 125 patients (22%) and NIL were significantly more frequent in MES positive patients (42%) than in MES negative patients at 48 h (15%; p = 0.002). MES at 48 h (OR 3.9; 95% CI 1.5 to 10; p = 0.005), atrial fibrillation (OR 3.6; 95% CI 1.3 to 11; p = 0.013) and arterial lesions (OR 4.3; 95% CI 1.5 to 12; p = 0.007) represented independent factors for NIL. CONCLUSION: The presence of MES at 48 h, atrial fibrillation and arterial lesions were associated with recurrence of cerebral ischaemia on DWI. PMID- 17846112 TI - Patients characteristics with cholinesterase inhibitor resistant hallucinations in dementia with Lewy bodies. PMID- 17846113 TI - Variability in language recovery after first-time stroke. AB - BACKGROUND: Predicting aphasia recovery after stroke has been difficult due to substantial variability in outcomes. Few studies have characterised the nature and extent of recovery, beginning with baselines at 24-72 hours after stroke onset. AIM: To characterise the course of language recovery after first-time stroke. METHODS: Using our Performance and Recovery in Stroke Study (PARIS) database, we evaluated consecutive first-time stroke patients with aphasia and diffusion-weighted-image-positive lesions on admission and at 90 days. RESULTS: Twenty-two of 91 patients had language disorders. Initial syndrome scores were positively correlated with 90-day scores (r = 0.60) and negatively correlated with the change in score from baseline to follow-up (r = -0.66). Neither lesion size, age nor education correlated with initial syndrome severity or with performance at 90 days. Level of education was not associated with degree of recovery. A multiple regression model that combined lesion size, age and initial syndrome was significant (p = 0.03) but only explained 29% of the variance. Patients with severe deficits at baseline in individual language domains could recover, improve to a less severe deficit or not improve at all. CONCLUSION: There was significant variability in language recovery after first-time stroke, even in more severe, initial syndromes. Traditional predictors of post-stroke language outcomes did not reliably predict function at 90 days. These data suggest that other factors that account for functional stroke recovery have not yet been identified. PMID- 17846114 TI - The utility of the Cambridge Behavioural Inventory in neurodegenerative disease. AB - We investigated the utility of the Cambridge Behavioural Inventory (CBI), a carer completed questionnaire, in a large cohort with Parkinson's disease (PD) (n = 215). In a sub-cohort of 112 patients with PD, the CBI was found to be a valid instrument compared with the Neuropsychiatric Inventory, PDQ-39 and UPDRS, with high internal consistency. Furthermore, in the whole cohort, the CBI was sensitive to changes in behaviour with disease progression. Comparison between CBI scores in PD and other neurodegenerative diseases, including Huntington's disease (HD) (n = 75), Alzheimer's disease (AD) (n = 96) and frontal variant frontotemporal dementia (fvFTD) (n = 64), revealed distinct profiles for each disease. Predominant deficits were "sleep"' and "self care" in PD; "memory" in HD and AD; and "motivation" and "stereotypic behaviours" in fvFTD. The CBI is a robust, easy-to-use and valid instrument, which has the capacity to discriminate between neurodegenerative diseases, and may be of value in monitoring therapeutic interventions. PMID- 17846115 TI - Deep brain stimulation in 18 patients with severe Gilles de la Tourette syndrome refractory to treatment: the surgery and stimulation. AB - BACKGROUND: There have been several reports of successful deep brain stimulation (DBS) for the treatment of severe Gilles de la Tourette syndrome (GTS). METHOD: 18 cases of GTS who were resistant to at least 6 months of standard and innovative treatments, as well as to psychobehavioural techniques, underwent DBS. DBS was placed bilaterally in the centromedian-parafascicular (CM-Pfc) and ventralis oralis complex of the thalamus. Patients were evaluated after surgery, with immediate and formal assessments at least every 3 months, including "on-off" and "sham off" in the first nine patients. RESULTS: All patients responded well to DBS, although to differing degrees. The duration of follow-up assessments ranged from 3 to 18 months. The comorbid symptoms of obsessive-compulsive behaviour, obsessive-compulsive disorder, self-injurious behaviours, anxiety and premonitory sensations decreased after treatment with DBS. There were no serious permanent adverse effects. CONCLUSIONS: DBS is a useful and safe treatment for severe GTS. The results of ours and previous DBS reports suggest that the CM-Pfc and ventralis oralis complex of the thalamus may be a good DBS target for GTS. PMID- 17846116 TI - Presentation of Toxoplasma gondii antigens via the endogenous major histocompatibility complex class I pathway in nonprofessional and professional antigen-presenting cells. AB - Challenge with the intracellular protozoan parasite Toxoplasma gondii induces a potent CD8+ T-cell response that is required for resistance to infection, but many questions remain about the factors that regulate the presentation of major histocompatibility complex class I (MHC-I)-restricted parasite antigens and about the role of professional and nonprofessional accessory cells. In order to address these issues, transgenic parasites expressing ovalbumin (OVA), reagents that track OVA/MHC-I presentation, and OVA-specific CD8+ T cells were exploited to compare the abilities of different infected cell types to stimulate CD8+ T cells and to define the factors that contribute to antigen processing. These studies reveal that a variety of infected cell types, including hematopoietic and nonhematopoietic cells, are capable of activating an OVA-specific CD8+ T-cell hybridoma, and that this phenomenon is dependent on the transporter associated with antigen processing and requires live T. gondii. Several experimental approaches indicate that T-cell activation is a consequence of direct presentation by infected host cells rather than cross-presentation. Surprisingly, nonprofessional antigen-presenting cells (APCs) were at least as efficient as dendritic cells at activating this MHC-I-restricted response. Studies to assess whether these cells are involved in initiation of the CD8+ T-cell response to T. gondii in vivo show that chimeric mice expressing MHC-I only in nonhematopoietic compartments are able to activate OVA-specific CD8+ T cells upon challenge. These findings associate nonprofessional APCs with the initial activation of CD8+ T cells during toxoplasmosis. PMID- 17846118 TI - Studies in target-based treatment. PMID- 17846117 TI - Delineation of species-specific binding properties of the CspZ protein (BBH06) of Lyme disease spirochetes: evidence for new contributions to the pathogenesis of Borrelia spp. AB - Borrelia burgdorferi CspZ (TIGR open reading frame designation, BBH06) is part of a functionally related group of proteins that bind one or more members of the factor H (FH) protein family. In this report we assess the conservation, distribution, properties, and ligand binding abilities of CspZ from the three main Borrelia species associated with Lyme disease infections in humans. CspZ (also referred to as BbCRASP-2 in the literature) was found to be highly conserved at the intraspecies level but divergent at the interspecies level. All CspZ orthologs that originated from B. burgdorferi isolates bound FH from a diverse group of mammals. In contrast, CspZ derived from B. garinii and B. afzelii did not. Regardless of the Borrelia species of origin, all CspZ proteins tested bound to unknown approximately 60-kDa serum proteins produced by different mammals. To further define the molecular basis for the differential binding of CspZ orthologs to host proteins, DNA sequence, truncation, and site-directed mutagenesis analyses were performed. DNA sequence analyses revealed that B. garinii and B. afzelii CspZ orthologs possess a 64-amino-acid N-terminal domain that is absent from B. burgdorferi CspZ. However, binding analyses of recombinant proteins revealed that this domain does not in and of itself influence ligand binding properties. Truncation and mutagenesis analyses further revealed that the key determinants required for ligand binding are discontinuous and that the presentation of the ligand binding pocket is dependent on alpha helices with high coiled-coil formation probability. The data presented here provide insight into the molecular basis of CspZ-ligand interactions and suggest that CspZ orthologs from diverse Borrelia species can contribute to the host-pathogen interaction through their interaction with serum proteins. PMID- 17846119 TI - USF1 recruits histone modification complexes and is critical for maintenance of a chromatin barrier. AB - The insulator element at the 5' end of the chicken beta-globin locus acts as a barrier, protecting transgenes against silencing effects of adjacent heterochromatin. We showed earlier that the transcription factor USF1 binds within the insulator and that this site is important for generating in adjacent nucleosomes histone modifications associated with active chromatin and, by inference, with barrier function. To understand the mechanism of USF1 action, we have characterized USF1-containing complexes. USF1 interacts directly with the histone H4R3-specific methyltransferase PRMT1. USF1, PRMT1, and the histone acetyltransferases (HATs) PCAF and SRC-1 form a complex with both H4R3 histone methyltransferase and HAT activities. Small interfering RNA downregulation of USF1 results in localized loss of H4R3 methylation, and other histone modifications associated with euchromatin, at the insulator. A dominant negative peptide that interferes with USF1 binding to DNA causes silencing of an insulated reporter construct, indicating abolition of barrier function. These results show that USF1 plays a direct role in maintaining the barrier, supporting a model in which the insulator works as a barrier by maintaining a local environment of active chromatin. PMID- 17846120 TI - SBP2 binding affinity is a major determinant in differential selenoprotein mRNA translation and sensitivity to nonsense-mediated decay. AB - Selenoprotein mRNAs are potential targets for degradation via nonsense-mediated decay due to the presence of in-frame UGA codons that can be decoded as either selenocysteine or termination codons. When UGA decoding is inefficient, as occurs when selenium is limiting, termination occurs at these positions. Based on the predicted exon-intron structure, 14 of the 25 human selenoprotein mRNAs are predicted to be sensitive to nonsense-mediated decay. Among these, sensitivity varies widely, resulting in a hierarchy of preservation or degradation of selenoprotein mRNAs and, thus, of selenoprotein synthesis. Potential factors in dictating the hierarchy of selenoprotein synthesis are the Sec insertion sequence RNA-binding proteins, SBP2 and nucleolin. To investigate the mechanistic basis for this hierarchy and the role of these two proteins, we carried out knockdowns of SBP2 expression and assessed the effects on selenoprotein mRNA levels. We also investigated in vivo binding of selenoprotein mRNAs by SBP2 and nucleolin via immunoprecipitation of the proteins and quantitation of bound mRNAs. We report that SBP2 exhibits strong preferential binding to some selenoprotein mRNAs over others, whereas nucleolin exhibits minimal differences in binding. Thus, SBP2 is a major determinant in dictating the hierarchy of selenoprotein synthesis via differential selenoprotein mRNA translation and sensitivity to nonsense-mediated decay. PMID- 17846121 TI - The Rap GTPase activator Drosophila PDZ-GEF regulates cell shape in epithelial migration and morphogenesis. AB - Epithelial morphogenesis is characterized by an exquisite control of cell shape and position. Progression through dorsal closure in Drosophila gastrulation depends on the ability of Rap1 GTPase to signal through the adherens junctional multidomain protein Canoe. Here, we provide genetic evidence that epithelial Rap activation and Canoe effector usage are conferred by the Drosophila PDZ-GEF (dPDZ GEF) exchange factor. We demonstrate that dPDZ-GEF/Rap/Canoe signaling modulates cell shape and apicolateral cell constriction in embryonic and wing disc epithelia. In dPDZ-GEF mutant embryos with strong dorsal closure defects, cells in the lateral ectoderm fail to properly elongate. Postembryonic dPDZ-GEF mutant cells generated in mosaic tissue display a striking extension of lateral cell perimeters in the proximity of junctional complexes, suggesting a loss of normal cell contractility. Furthermore, our data indicate that dPDZ-GEF signaling is linked to myosin II function. Both dPDZ-GEF and cno show strong genetic interactions with the myosin II-encoding gene, and myosin II distribution is severely perturbed in epithelia of both mutants. These findings provide the first insight into the molecular machinery targeted by Rap signaling to modulate epithelial plasticity. We propose that dPDZ-GEF-dependent signaling functions as a rheostat linking Rap activity to the regulation of cell shape in epithelial morphogenesis at different developmental stages. PMID- 17846122 TI - Unstable spinocerebellar ataxia type 10 (ATTCT*(AGAAT) repeats are associated with aberrant replication at the ATX10 locus and replication origin-dependent expansion at an ectopic site in human cells. AB - Spinocerebellar ataxia type 10 (SCA10) is associated with expansion of (ATTCT)n repeats (where n is the number of repeats) within the ataxin 10 (ATX10/E46L) gene. The demonstration that (ATTCT)n tracts can act as DNA unwinding elements (DUEs) in vitro has suggested that aberrant replication origin activity occurs at expanded (ATTCT)n tracts and may lead to their instability. Here, we confirm these predictions. The wild-type ATX10 locus displays inefficient origin activity, but origin activity is elevated at the expanded ATX10 loci in patient derived cells. To test whether (ATTCT)n tracts can potentiate origin activity, cell lines were constructed that contain ectopic copies of the c-myc replicator in which the essential DUE was replaced by ATX10 DUEs with (ATTCT)n. ATX10 DUEs containing (ATTCT)27 or (ATTCT)48, but not (ATTCT)8 or (ATTCT)13, could substitute functionally for the c-myc DUE, but (ATTCT)48 could not act as an autonomous replicator. Significantly, chimeric c-myc replicators containing ATX10 DUEs displayed length-dependent (ATTCT)n instability. By 250 population doublings, dramatic two- and fourfold length expansions were observed for (ATTCT)27 and (ATTCT)48 but not for (ATTCT)8 or (ATTCT)13. These results implicate replication origin activity as one molecular mechanism associated with the instability of (ATTCT)n tracts that are longer than normal length. PMID- 17846123 TI - Accurate homologous recombination is a prominent double-strand break repair pathway in mammalian chromosomes and is modulated by mismatch repair protein Msh2. AB - We designed DNA substrates to study intrachromosomal recombination in mammalian chromosomes. Each substrate contains a thymidine kinase (tk) gene fused to a neomycin resistance (neo) gene. The fusion gene is disrupted by an oligonucleotide containing the 18-bp recognition site for endonuclease I-SceI. Substrates also contain a "donor" tk sequence that displays 1% or 19% sequence divergence relative to the tk portion of the fusion gene. Each donor serves as a potential recombination partner for the fusion gene. After stably transfecting substrates into mammalian cell lines, we investigated spontaneous recombination and double-strand break (DSB)-induced recombination following I-SceI expression. No recombination events between sequences with 19% divergence were recovered. Strikingly, even though no selection for accurate repair was imposed, accurate conservative homologous recombination was the predominant DSB repair event recovered from rodent and human cell lines transfected with the substrate containing sequences displaying 1% divergence. Our work is the first unequivocal demonstration that homologous recombination can serve as a major DSB repair pathway in mammalian chromosomes. We also found that Msh2 can modulate homologous recombination in that Msh2 deficiency promoted discontinuity and increased length of gene conversion tracts and brought about a severalfold increase in the overall frequency of DSB-induced recombination. PMID- 17846124 TI - Identification of type 2 diabetes genes in Mexican Americans through genome-wide association studies. AB - OBJECTIVE: The objective of this study was to identify DNA polymorphisms associated with type 2 diabetes in a Mexican-American population. RESEARCH DESIGN AND METHODS: We genotyped 116,204 single nucleotide polymorphisms (SNPs) in 281 Mexican Americans with type 2 diabetes and 280 random Mexican Americans from Starr County, Texas, using the Affymetrix GeneChip Human Mapping 100K set. Allelic association exact tests were calculated. Our most significant SNPs were compared with results from other type 2 diabetes genome-wide association studies (GWASs). Proportions of African, European, and Asian ancestry were estimated from the HapMap samples using structure for each individual to rule out spurious association due to population substructure. RESULTS: We observed more significant allelic associations than expected genome wide, as empirically assessed by permutation (14 below a P of 1 x 10(-4) [8.7 expected]). No significant differences were observed between the proportion of ancestry estimates in the case and random control sets, suggesting that the association results were not likely confounded by substructure. A query of our top approximately 1% of SNPs (P < 0.01) revealed SNPs in or near four genes that showed evidence for association (P < 0.05) in multiple other GWAS interrogated: rs979752 and rs10500641 near UBQLNL and OR52H1 on chromosome 11, rs2773080 and rs3922812 in or near RALGPS2 on chromosome 1, and rs1509957 near EGR2 on chromosome 10. CONCLUSIONS: We identified several SNPs with suggestive evidence for replicated association with type 2 diabetes that merit further investigation. PMID- 17846125 TI - A search for variants associated with young-onset type 2 diabetes in American Indians in a 100K genotyping array. AB - OBJECTIVE: To identify genetic variants in linkage disequilibrium with those conferring diabetes susceptibility, a genome-wide association study for young onset diabetes was conducted in an American-Indian population. RESEARCH DESIGN AND METHODS: Data come from 300 case subjects with type 2 diabetes with age of onset <25 years and 334 nondiabetic control subjects aged >or=45 years. To provide for tests of within-family association, 121 nondiabetic siblings of case subjects were included along with 140 diabetic siblings of control subjects (172 sibships). Individuals were genotyped on the Affymetrix 100K array, resulting in 80,044 usable single nucleotide polymorphisms (SNPs). SNPs were analyzed for within-family association and for general association in case and control subjects, and these tests were combined by Fisher's method, with priority given to the within-family test. RESULTS: There were more SNPs with low P values than expected theoretically under the global null hypothesis of no association, and 128 SNPs had evidence for association at P < 0.001. The association of these SNPs with diabetes was further investigated in 1,207 diabetic and 1,627 nondiabetic individuals from the population study who were not included in the genome-wide study. SNPs from 10 genomic regions showed evidence for replication at P < 0.05. These included SNPs on chromosome 3 near ZNF659, chromosome 11 near FANCF, chromosome 11 near ZBTB15, and chromosome 12 near SENP1. CONCLUSIONS: These studies suggest several regions where marker alleles are potentially in linkage disequilibrium with variants that confer susceptibility to young-onset type 2 diabetes in American Indians. PMID- 17846126 TI - Identification of novel candidate genes for type 2 diabetes from a genome-wide association scan in the Old Order Amish: evidence for replication from diabetes related quantitative traits and from independent populations. AB - OBJECTIVE: We sought to identify type 2 diabetes susceptibility genes through a genome-wide association scan (GWAS) in the Amish. RESEARCH DESIGN AND METHODS: DNA from 124 type 2 diabetic case subjects and 295 control subjects with normal glucose tolerance were genotyped on the Affymetrix 100K single nucleotide polymorphism (SNP) array. A total of 82,485 SNPs were tested for association with type 2 diabetes. Type 2 diabetes-associated SNPs were further prioritized by the following: 1) associations with 5 oral glucose tolerance test (OGTT) traits in 427 nondiabetic Amish subjects, and 2) in silico replication from three independent 100L SNP GWASs (Framingham Heart Study Caucasians, Pima Indians, and Mexican Americans) and a 500K GWAS in Scandinavians. RESULTS: The strongest association (P = 1.07 x 10(-5)) was for rs2237457, which is located in growth factor receptor-bound protein 10 (Grb10), an adaptor protein that regulate insulin receptor signaling. rs2237457 was also strongly associated with OGTT glucose area under the curve in nondiabetic subjects (P = 0.001). Of the 1,093 SNPs associated with type 2 diabetes at P < 0.01, 67 SNPs demonstrated associations with at least one OGTT trait in nondiabetic individuals; 80 SNPs were nominally associated with type 2 diabetes in one of the three independent 100K GWASs, 3 SNPs (rs2540317 in MFSD9, rs10515353 on chromosome 5, and rs2242400 in BCAT1 were associated with type 2 diabetes in more than one population), and 11 SNPs were nominally associated with type 2 diabetes in Scandinavians. One type 2 diabetes-associated SNP (rs3845971, located in FHIT) showed replication with OGTT traits and also in another population. CONCLUSIONS: Our GWAS of type 2 diabetes identified several gene variants associated with type 2 diabetes, some of which are worthy of further study. PMID- 17846127 TI - Molecular epidemiology of clinical isolates of carbapenem-resistant Acinetobacter spp. from Chinese hospitals. AB - Carbapenem resistance in Acinetobacter spp. is an emerging problem in China. We investigated the molecular epidemiology and carbapenemase genes of 221 nonrepetitive imipenem-resistant clinical isolates of Acinetobacter spp. collected from 1999 to 2005 at 11 teaching hospitals in China. Genotyping by pulsed-field gel electrophoresis (PFGE) found 15 PFGE patterns. Of these, one (clone P) was identified at four hospitals in Beijing and another (clone A) at four geographically disparate cities. Most imipenem-resistant isolates exhibited high-level resistance to all beta-lactams and were only susceptible to colistin. bla(OXA-23)-like genes were found in 97.7% of isolates. Sequencing performed on 60 representative isolates confirmed the presence of the bla(OXA-23) carbapenemase gene. Analysis of the genetic context of bla(OXA-23) showed the presence of ISAba1 upstream of bla(OXA-23). All of the 187 A. baumannii isolates identified by amplified RNA gene restriction analysis carried a bla(OXA-51)-like oxacillinase gene, while this gene was absent from isolates of other species. Sequencing indicated the presence of bla(OXA-66) for 18 representative isolates. Seven isolates of one clone (clone T) carried the plasmid-mediated bla(OXA-58) carbapenemase gene, while one isolate of another clone (clone L) carried the bla(OXA-72) carbapenemase gene. Only 1 isolate of clone Q carried the bla(IMP-8) metallo-beta-lactamase gene, located in a class 1 integron. Of 221 isolates, 77.8% carried bla(PER-1)-like genes. Eleven different structures of class 1 integrons were detected, and most integrons carried genes mediating resistance to aminoglycosides, rifampin, and chloramphenicol. These findings indicated clonal spread of imipenem-resistant Acinetobacter spp. and wide dissemination of the OXA 23 carbapenemase in China. PMID- 17846128 TI - Lack of correlation between embB mutation and ethambutol MIC in Mycobacterium tuberculosis clinical isolates from China. AB - Seventy-four Mycobacterium tuberculosis clinical isolates from China were subjected to drug susceptibility testing using ethambutol, isoniazid, rifampin, and ofloxacin. The results revealed that the presence of embB mutations did not correlate with ethambutol resistance but was associated with multiple-drug resistance, especially resistance to both ethambutol and rifampin. PMID- 17846129 TI - Clinical and pharmacological determinants of the therapeutic response to dihydroartemisinin-piperaquine for drug-resistant malaria. AB - Dihydroartemisinin-piperaquine (DHP) is an important new treatment for drug resistant malaria, although pharmacokinetic studies on the combination are limited. In Papua, Indonesia, we assessed determinants of the therapeutic efficacy of DHP for uncomplicated malaria. Plasma piperaquine concentrations were measured on day 7 and day 28, and the cumulative risk of parasitological failure at day 42 was calculated using survival analysis. Of the 598 patients in the evaluable population 342 had infections with Plasmodium falciparum, 83 with Plasmodium vivax, and 173 with a mixture of both species. The unadjusted cumulative risks of recurrence were 7.0% (95% confidence interval [CI]: 4.6 to 9.4%) for P. falciparum and 8.9% (95% CI: 6.0 to 12%) for P. vivax. After correcting for reinfections the risk of recrudescence with P. falciparum was 1.1% (95% CI: 0.1 to 2.1%). The major determinant of parasitological failure was the plasma piperaquine concentration. A concentration below 30 ng/ml on day 7 was observed in 38% (21/56) of children less than 15 years old and 22% (31/140) of adults (P = 0.04), even though the overall dose (mg per kg of body weight) in children was 9% higher than that in adults (P < 0.001). Patients with piperaquine levels below 30 ng/ml were more likely to have a recurrence with P. falciparum (hazard ratio [HR] = 6.6 [95% CI: 1.9 to 23]; P = 0.003) or P. vivax (HR = 9.0 [95% CI: 2.3 to 35]; P = 0.001). The plasma concentration of piperaquine on day 7 was the major determinant of the therapeutic response to DHP. Lower plasma piperaquine concentrations and higher failure rates in children suggest that dose revision may be warranted in this age group. PMID- 17846130 TI - Antimicrobial effect of halocidin-derived peptide in a mouse model of Listeria infection. AB - Halocidin is an antimicrobial peptide found in the tunicate. A series of experiments were previously conducted in an attempt to develop a novel antibiotic derived from halocidin, as the peptide was determined to evidence profound antimicrobial activity against a variety of antibiotic-resistant microbes, with significantly less toxicity to human blood cells. In this study, we assessed the validity of one of the halocidin congeners, called Khal, as a new antibiotic for the treatment of systemic bacterial infections. Our in vitro antimicrobial tests showed that the MICs of Khal against several gram-positive bacteria were below 16 microg/ml in the presence of salt. We also determined that Khal retained sufficient target selectivity to discern microbial and human blood cells and was therefore capable of efficiently killing invading pathogens. Furthermore, Khal caused no aggregation problems upon incubation with human serum and also proved to be resistant to proteolysis by enzymes occurring in human serum. In the following experiments conducted with a mouse model of Listeria monocytogenes infection, we demonstrated that a single intravenous inoculation with Khal resulted in significant therapeutic effects on the survival of mice. In addition, our bacterial-enumeration analysis showed that after Listeria infection, livers and spleens from Khal-treated mice generated a great deal fewer recoverable CFU. Finally, the antibiotic effects of Khal were evaluated under confocal microscopy after we immunostained the liver sections with anti-Khal antibody. It was concluded that Khal bound specifically to the surfaces of bacteria colonized in the mouse liver and killed the bacteria rapidly. PMID- 17846131 TI - Small-molecule scaffolds for CYP51 inhibitors identified by high-throughput screening and defined by X-ray crystallography. AB - Sterol 14alpha-demethylase (CYP51), a major checkpoint in membrane sterol biosynthesis, is a key target for fungal antibiotic therapy. We sought small organic molecules for lead candidate CYP51 inhibitors. The changes in CYP51 spectral properties following ligand binding make CYP51 a convenient target for high-throughput screening technologies. These changes are characteristic of either substrate binding (type I) or inhibitor binding (type II) in the active site. We screened a library of 20,000 organic molecules against Mycobacterium tuberculosis CYP51 (CYP51(Mt)), examined the top type I and type II binding hits for their inhibitory effects on M. tuberculosis in broth culture, and analyzed them spectrally for their ability to discriminate between CYP51(Mt) and two reference M. tuberculosis CYP proteins, CYP130 and CYP125. We determined the binding mode for one of the top type II hits, alpha-ethyl-N-4-pyridinyl benzeneacetamide (EPBA), by solving the X-ray structure of the CYP51(Mt)-EPBA complex to a resolution of 1.53 A. EPBA binds coordinately to the heme iron in the CYP51(Mt) active site through a lone pair of nitrogen electrons and also through hydrogen bonds with residues H259 and Y76, which are invariable in the CYP51 family, and hydrophobic interactions in a phylum- and/or substrate-specific cavity of CYP51. We also identified a second compound with structural and binding properties similar to those of EPBA, 2-(benzo[d]-2,1,3-thiadiazole-4-sulfonyl)-2 amino-2-phenyl-N-(pyridinyl-4)-acetamide (BSPPA). The congruence between the geometries of EPBA and BSPPA and the CYP51 binding site singles out EPBA and BSPPA as lead candidate CYP51 inhibitors with optimization potential for efficient discrimination between host and pathogen enzymes. PMID- 17846132 TI - Pharmacokinetics of acyclovir after intravenous infusion of acyclovir and after oral administration of acyclovir and its prodrug valacyclovir in healthy adult horses. AB - The purpose of this study was twofold. The first aim was to evaluate the oral bioavailability and pharmacokinetics (PKs) of acyclovir in horses after intravenous (i.v.) administration and after oral administration of acyclovir and its prodrug, valacyclovir. Second, we aimed to combine these PK data with pharmacodynamic (PD) information, i.e., 50% effective concentrations (EC(50) values) from in vitro studies, to design an optimal dosage schedule. Three treatments were administered to healthy adult horses: 10 mg of acyclovir/kg of body weight delivered as an i.v. infusion over 1 h, 20 mg of acyclovir/kg administered as tablets by nasogastric intubation, and 20 mg of valacyclovir/kg administered as tablets by nasogastric intubation. Total plasma concentrations were measured by a high-performance liquid chromatography method combined with fluorescence detection, while unbound plasma concentrations were determined by liquid chromatography-tandem mass spectrometry. The peak concentration of i.v. acyclovir was approximately 10 mug/ml for both the total and the unbound plasma concentrations. The mean half-life of elimination was between 5.05 h (total concentration) and 11.9 h (unbound concentration). Oral administration of acyclovir resulted in low maximum concentration in plasma (C(max)) and poor bioavailability. A 10-times-higher C(max) and an 8-times-higher bioavailability were achieved with oral administration of valacyclovir. The i.v. administration of 10 mg/kg acyclovir and the oral administration of 20 mg/kg valacyclovir achieved concentrations within the sensitivity range of equine herpesvirus type 1 (EHV-1). The higher bioavailability of valacyclovir makes it an attractive candidate for the prophylactic and/or therapeutic treatment of horses infected with EHV-1. The results from the PK/PD modeling showed that a dosage of 40 mg/kg valacyclovir, administered three times daily, would be sufficient to reach plasma concentrations above the EC(50) values. PMID- 17846134 TI - Molecular and biochemical characterization of the chromosome-encoded class A beta lactamase BCL-1 from Bacillus clausii. AB - A chromosomal beta-lactamase gene from Bacillus clausii NR, which is used as a probiotic, was cloned and expressed in Escherichia coli. It encodes a clavulanic acid-susceptible Ambler class A beta-lactamase, BCL-1, with a pI of 5.5 and a molecular mass of ca. 32 kDa. It shares 91% and 62% amino acid identity with the chromosomally encoded PenP penicillinases from B. clausii KSM-K16 and Bacillus licheniformis, respectively. The hydrolytic profile of this beta-lactamase includes penicillins, narrow-spectrum cephalosporins, and cefpirome. This chromosome-encoded enzyme was inducible in B. clausii, and its gene is likely related to upstream-located regulatory genes that share significant identity with those reported to be upstream of the penicillinase gene of B. licheniformis. The bla(BCL-1) gene was located next to the known chromosomal aadD2 gene and the erm34 gene, which encode resistance to aminoglycosides and macrolides, respectively. Similar genes were found in a collection of B. clausii reference strains. PMID- 17846133 TI - Interpretation of antibiotic concentration ratios measured in epithelial lining fluid. PMID- 17846135 TI - Interaction study of the combined use of paroxetine and fosamprenavir-ritonavir in healthy subjects. AB - Human immunodeficiency virus-infected patients have an increased risk for depression. Despite the high potential for drug-drug interactions, limited data on the combined use of antidepressants and antiretrovirals are available. Theoretically, ritonavir-boosted protease inhibitors may inhibit CYP2D6-mediated metabolism of paroxetine. We wanted to determine the effect of fosamprenavir ritonavir on paroxetine pharmacokinetics and vice versa and to evaluate the safety of the combination. Group A started with 20 mg paroxetine every day for 10 days; after a wash-out period of 16 days, subjects received paroxetine (20 mg every day) plus fosamprenavir-ritonavir (700/100 mg twice a day) from days 28 to 37. Group B received the regimens in reverse order. On days 10 and 37, pharmacokinetic curves were recorded. Twenty-six healthy subjects (18 females, 8 males) were included. Median (range) age and weight were 44.4 (18.2 to 64.3) years and 68.8 (51.0 to 89.4) kg. Three subjects were excluded (two because of adverse events; one for nonadherence). Addition of fosamprenavir-ritonavir to paroxetine resulted in a significant decrease in paroxetine exposure: the geometric mean ratios (90% confidence intervals) of paroxetine plus fosamprenavir ritonavir to paroxetine alone were 0.45 (0.41 to 0.49) for the area under the concentration-time curve from 0 to 24 h (AUC(0-24)), 0.49 (0.45 to 0.53) for the maximum concentration of the drug in plasma (C(max)), and 0.75 (0.71 to 0.80) for the apparent elimination half-life (t(1/2)). The free fraction of paroxetine showed a median (interquartile range) increase of 30% (18 to 42%) after the addition of fosamprenavir-ritonavir. The AUC(0-12), C(max), C(min), and t(1/2) of amprenavir and ritonavir were similar to those of historical controls. No serious adverse events occurred. Fosamprenavir-ritonavir reduced total paroxetine exposure by 55%. This is partly explained by protein displacement of paroxetine. We think that this interaction is clinically relevant and that titration to a higher dose of paroxetine may be necessary to accomplish the needed antidepressant effect. PMID- 17846136 TI - Emergence of the quinolone resistance-mediating gene aac(6')-Ib-cr in extended spectrum-beta-lactamase-producing Klebsiella isolates collected in Slovenia between 2000 and 2005. AB - Seventy-four nonrepetitive uropathogenic fluoroquinolone-resistant or intermediate extended-spectrum-beta-lactamase-producing Klebsiella isolates from Slovenia were screened for the presence of plasmid-mediated quinolone resistance genes. None of the known qnr genes were detected. The aac(6')-Ib-cr allele was detected on plasmids from 25 transconjugants for which the ciprofloxacin MIC was higher than for the recipient Escherichia coli strain. PMID- 17846137 TI - Effect of oral treatment with hexadecyloxypropyl-[(S)-9-(3-hydroxy-2- phosphonylmethoxypropyl)adenine] [(S)-HPMPA] or octadecyloxyethyl-(S)-HPMPA on cowpox or vaccinia virus infections in mice. AB - We have previously reported that (S)-9-(3-hydroxy-2 phosphonylmethoxypropyl)adenine, or (S)-HPMPA, is active in vitro against cowpox virus (CV) and vaccinia virus (VV) but is not active orally in animals. However, the ether lipid esters of (S)-HPMPA, hexadecyloxypropyl-[(S)-HPMPA] [HDP-(S) HPMPA] and octadecyloxyethyl-[(S)-HPMPA] [ODE-(S)-HPMPA], had significantly enhanced activity in vitro and are orally bioavailable in mice. In the current study, HDP-(S)-HPMPA and ODE-(S)-HPMPA were prepared in water and administered once daily by oral gavage to mice at doses of 30, 10, and 3 mg/kg of body weight for 5 days beginning 24, 48, or 72 h after inoculation with CV or VV. Oral HDP (S)-HPMPA and ODE-(S)-HPMPA were both highly effective (P < 0.001) at preventing mortality due to CV at 30 mg/kg, even when treatments were delayed until up to 72 h postinfection. ODE-(S)-HPMPA or HDP-(S)-HPMPA were also highly effective (P < 0.001) at preventing mortality in mice infected with VV at 30 mg/kg when treatments were delayed until to 48 or 72 h postinfection, respectively. Protection against both viruses was associated with a significant reduction of virus replication in the liver, spleen, and kidney but not in the lung. These data indicate that HDP-(S)-HPMPA and ODE-(S)-HPMPA are active when given orally against lethal CV and VV infections in mice, and further evaluation is warranted to provide additional information on the potential of these orally active compounds for treatment of human orthopoxvirus infection. PMID- 17846139 TI - Evaluation of tigecycline penetration into colon wall tissue and epithelial lining fluid using a population pharmacokinetic model and Monte Carlo simulation. AB - The objective of these analyses was to assess the penetration of tigecycline into colon wall tissue and epithelial lining fluid (ELF). The analyses included data from subjects without infection (phase 1) and patients with intra-abdominal infections (phase 2/3). Steady-state serum samples were collected from all subjects/patients (n = 577), while colon wall specimens (n = 23) and ELF specimens (n = 30) were obtained from subjects without infection. Tissue and serum data were simultaneously comodeled by using the BigNPAG program, and a four compartment, open model with zero-order intravenous input and first-order elimination was employed. To examine the full range of tissue penetration and the associated probabilities of occurrence, a 9,999-subject Monte Carlo simulation was performed with two outputs, one for ELF penetration and one for colon wall tissue penetration. Data were well fit using models described above, with all r(2) values above 0.95. For subjects without infection, the median (5th and 95th percentiles) colon wall and ELF penetration ratios were 1.73 (0.160 and 199) and 1.15 (0.561 and 5.23), respectively. Simulation results predict that tissue penetration varies considerably and likely explain unexpected clinical outcomes for those patients infected with strains at margins of the MIC distribution. PMID- 17846138 TI - Design, synthesis, and evaluation of 10-N-substituted acridones as novel chemosensitizers in Plasmodium falciparum. AB - A series of novel 10-N-substituted acridones, bearing alkyl side chains with tertiary amine groups at the terminal position, were designed, synthesized, and evaluated for the ability to enhance the potency of quinoline drugs against multidrug-resistant (MDR) Plasmodium falciparum malaria parasites. A number of acridone derivatives, with side chains bridged three or more carbon atoms apart between the ring nitrogen and terminal nitrogen, demonstrated chloroquine (CQ) chemosensitizing activity against the MDR strain of P. falciparum (Dd2). Isobologram analysis revealed that selected candidates demonstrated significant synergy with CQ in the CQ-resistant (CQR) parasite Dd2 but only additive (or indifferent) interaction in the CQ-sensitive (CQS) D6. These acridone derivatives also enhanced the sensitivity of other quinoline antimalarials, such as desethylchloroquine (DCQ) and quinine (QN), in Dd2. The patterns of chemosensitizing effects of selected acridones on CQ and QN were similar to those of verapamil against various parasite lines with mutations encoding amino acid 76 of the P. falciparum CQ resistance transporter (PfCRT). Unlike other known chemosensitizers with recognized psychotropic effects (e.g., desipramine, imipramine, and chlorpheniramine), these novel acridone derivatives exhibited no demonstrable effect on the uptake or binding of important biogenic amine neurotransmitters. The combined results indicate that 10-N-substituted acridones present novel pharmacophores for the development of chemosensitizers against P. falciparum. PMID- 17846140 TI - Antibiotic resistance and single-nucleotide polymorphism cluster grouping type in a multinational sample of resistant Mycobacterium tuberculosis isolates. AB - A single-nucleotide polymorphism-based cluster grouping (SCG) classification system for Mycobacterium tuberculosis was used to examine antibiotic resistance type and resistance mutations in relationship to specific evolutionary lineages. Drug resistance and resistance mutations were seen across all SCGs. SCG-2 had higher proportions of katG codon 315 mutations and resistance to four drugs. PMID- 17846141 TI - Randomized, double-blind, placebo-controlled trial of cephalexin for treatment of uncomplicated skin abscesses in a population at risk for community-acquired methicillin-resistant Staphylococcus aureus infection. AB - Empirical use of beta-lactam antibiotics, the preferred agents for treating uncomplicated skin and soft tissue infections, may no longer be appropriate for these infections because of the increasing prevalence of community strains of methicillin-resistant Staphylococcus aureus (MRSA). Retrospective studies, however, suggest that outcomes are good even when beta-lactams are used. We conducted a randomized, double-blind trial of 166 outpatient subjects comparing placebo to cephalexin at 500 mg orally four times for 7 days after incision and drainage of skin and soft tissue abscesses. The primary outcome was clinical cure or failure 7 days after incision and drainage. S. aureus was isolated from 70.4% of abscess cultures. Of the isolates tested 87.8% were MRSA, 93% of which were positive for Panton-Valentine leucocidin genes. Clinical cure rates were 90.5% (95% confidence interval, 0.82 to 0.96) in the 84 placebo recipients and 84.1% (95% confidence interval, 0.74 to 0.91) in the 82 cephalexin recipients (difference in the two proportions, 0.0006; 95% confidence interval, -0.0461 to 0.0472; P = 0.25). The 90.5% cure rate observed in the placebo arm and 84.1% cure rate observed in the cephalexin arm provide strong evidence that antibiotics may be unnecessary after surgical drainage of uncomplicated skin and soft tissue abscesses caused by community strains of MRSA. PMID- 17846142 TI - Tn6001, a transposon-like element containing the blaVIM-3-harboring integron In450. AB - We describe the structure of a transposon-like element named Tn6001, which contains a bla(VIM-3)-harboring integron In450, which was derived from a multidrug-resistant Pseudomonas aeruginosa clinical isolate in Taiwan. The transposon backbone structure is most closely related to those of Tn1404* and Tn1403. Tn6001 was inserted into the chromosome of the clinical isolate. PMID- 17846143 TI - Global phenotype screening and transcript analysis outlines the inhibitory mode(s) of action of two amphibian-derived, alpha-helical, cationic peptides on Saccharomyces cerevisiae. AB - Dermaseptin S3(1-16) [DsS3(1-16)] and magainin 2 (Mag 2) are two unrelated, amphibian-derived cationic peptides that adopt an alpha-helical structure within microbial membranes and have been proposed to kill target organisms via membrane disruption. Using a combination of global deletion mutant library phenotypic screening, expression profiling, and physical techniques, we have carried out a comprehensive in vitro analysis of the inhibitory action of these two peptides on the model fungus Saccharomyces cerevisiae. Gene ontology profiling (of biological processes) was used to identify both common and unique effects of each peptide. Resistance to both peptides was conferred by genes involved in telomere maintenance, chromosome organization, and double-strand break repair, implicating a common inhibitory action of DNA damage. Crucially, each peptide also required unique genes for maintaining resistance; for example, DsS3(1-16) required genes involved in protein targeting to the vacuole, and Mag 2 required genes involved in DNA-dependent DNA replication and DNA repair. Thus, DsS3(1-16) and Mag 2 have both common and unique antifungal actions that are not simply due to membrane disruption. Physical techniques revealed that both peptides interacted with DNA in vitro but in subtly different ways, and this observation was supported by the functional genomics experiments that provided evidence that both peptides also interfered with DNA integrity differently in vivo. This implies that both peptides are able to pass through the cytoplasmic membrane of yeast cells and damage DNA, an inhibitory action that has not been previously attributed to either of these peptides. PMID- 17846144 TI - In vitro infection model characterizing the effect of efflux pump inhibition on prevention of resistance to levofloxacin and ciprofloxacin in Streptococcus pneumoniae. AB - The prevalence of fluoroquinolone-resistant Streptococcus pneumoniae is slowly rising as a consequence of the increased use of fluoroquinolone antibiotics to treat community-acquired pneumonia. We tested the hypothesis that increased efflux pump (EP) expression by S. pneumoniae may facilitate the emergence of fluoroquinolone resistance. By using an in vitro pharmacodynamic infection system, a wild-type S. pneumoniae strain (Spn-058) and an isogenic strain with EP overexpression (Spn-RC2) were treated for 10 days with ciprofloxacin or levofloxacin in the presence or absence of the EP inhibitor reserpine to evaluate the effect of EP inhibition on the emergence of resistance. Cultures of Spn-058 and Spn-RC2 were exposed to concentration-time profiles simulating those in humans treated with a regimen of ciprofloxacin at 750 mg orally once every 12 h and with regimens of levofloxacin at 500 and 750 mg orally once daily (QD; with or without continuous infusions of 20 microg of reserpine/ml). The MICs of ciprofloxacin and levofloxacin for Spn-058 were both 1 microg/ml when susceptibility testing was conducted with each antibiotic alone and with each antibiotic in the presence of reserpine. For Spn-RC2, the MIC of levofloxacin alone and with reserpine was also 1 mug/ml; the MICs of ciprofloxacin were 2 and 1 microg/ml, respectively, when determined with ciprofloxacin alone and in combination with reserpine. Reserpine, alone, had no effect on the growth of Spn 058 and Spn-RC2. For Spn-058, simulated regimens of ciprofloxacin at 750 mg every 12 h or levofloxacin at 500 mg QD were associated with the emergence of fluoroquinolone resistance. However, the use of ciprofloxacin at 750 mg every 12 h and levofloxacin at 500 mg QD in combination with reserpine rapidly killed Spn 058 and prevented the emergence of resistance. For Spn-RC2, levofloxacin at 500 mg QD was associated with the emergence of resistance, but again, the resistance was prevented when this levofloxacin regimen was combined with reserpine. Ciprofloxacin at 750 mg every 12 h also rapidly selected for ciprofloxacin resistant mutants of Spn-RC2. However, the addition of reserpine to ciprofloxacin therapy only delayed the emergence of resistance. Levofloxacin at 750 mg QD, with and without reserpine, effectively eradicated Spn-058 and Spn-RC2 without selecting for fluoroquinolone resistance. Ethidium bromide uptake and efflux studies demonstrated that, at the baseline, Spn-RC2 had greater EP expression than Spn-058. These studies also showed that ciprofloxacin was a better inducer of EP expression than levofloxacin in both Spn-058 and Spn-RC2. However, in these isolates, the increase in EP expression by short-term exposure to ciprofloxacin and levofloxacin was transient. Mutants of Spn-058 and Spn-RC2 that emerged under suboptimal antibiotic regimens had a stable increase in EP expression. Levofloxacin at 500 mg QD in combination with reserpine, an EP inhibitor, or at 750 mg QD alone killed wild-type S. pneumoniae and strains that overexpressed reserpine-inhibitable EPs and was highly effective in preventing the emergence of fluoroquinolone resistance in S. pneumoniae during therapy. Ciprofloxacin at 750 mg every 12 h, as monotherapy, was ineffective for the treatment of Spn-058 and Spn-RC2. Ciprofloxacin in combination with reserpine prevented the emergence of resistance in Spn-058 but not in Spn-RC2, the EP-overexpressing strain. PMID- 17846145 TI - Isn't it the right time to address the impact of pediatric cardiac intensive care units on medical education? PMID- 17846146 TI - School-based health centers: improving access and quality of care for low-income adolescents. AB - OBJECTIVES: We sought to compare visit rates, emergency care use, and markers of quality of care between adolescents who use school-based health centers and those who use other community centers within a safety-net health care system for low income and uninsured patients. PATIENTS AND METHODS: In this retrospective cohort study we used Denver Health electronic medical chart data, the Denver Health immunization registry, and Denver Public Schools enrollment data for the period from August 1, 2002, to July 31, 2003. The cohort included all 14- to 17-year-old Denver Public Schools high school enrollees who were active Denver Health patients and were either uninsured or insured by Medicaid or the State Children's Health Insurance Program. "School-based health center users" were those who had used a Denver Health school-based health center; "other users" were those who had used a Denver Health community clinic but not a school-based health center. Markers of quality included having a health maintenance visit and receipt of an influenza vaccine, tetanus booster, and hepatitis B vaccine if indicated. Multiple logistic regression analysis that controlled for gender, race/ethnicity, insurance status, chronic illness, and visit rate was used to compare school based health center users to other users. RESULTS: Although school-based health center users (n = 790) were less likely than other users (n = 925) to be insured (37% vs 73%), they were more likely to have made > or = 3 primary care visits (52% vs 34%), less likely to have used emergency care (17% vs 34%), and more likely to have received a health maintenance visit (47% vs 33%), an influenza vaccine (45% vs 18%), a tetanus booster (33% vs 21%), and a hepatitis B vaccine (46% vs 20%). CONCLUSIONS: These findings suggest that, within a safety-net system, school-based health centers augment access to care and quality of care for underserved adolescents compared with traditional outpatient care sites. PMID- 17846147 TI - Efficacy of highly active antiretroviral therapy in HIV-1 infected children in Kenya. AB - OBJECTIVE: Few studies have investigated the efficacy of antiretroviral therapy among HIV-infected children in resource-poor settings. This observational, retrospective analysis describes the clinical, immunologic, and virologic effects of highly active antiretroviral therapy in treatment-naive, HIV-infected children in Mombasa, Kenya. In keeping with a public health approach, all children were treated by using a simplified, nationally approved, triple-drug regimen. METHODS: Clinical data and stored plasma samples from 29 children who were followed prospectively between April 2003 and October 2004 were analyzed. All children received generic formulations of nevirapine, zidovudine, and lamivudine and were evaluated at baseline and at 3, 6, 9, 12, and 15 months. At each visit, weight and CD4 lymphocyte counts were measured and plasma samples were stored for analysis. HIV RNA load was determined retrospectively at baseline and 9 months after initiation of therapy. RESULTS: The mean age of the children was 8.5 years (range: 2-16 years). At baseline, the mean CD4 count (+/-SD) was 182.3 x 10(6) cells per microL (+/-145.6). On treatment, CD4 counts increased step-wise by a mean of 187 x 10(6) cells per microL at 3 months, 293 cells per microL at 6 months, 308 cells per microL at 9 months, 334 cells per microL at 12 months, and 363 cells per microL at 15 months. The mean plasma viral load decreased from a baseline level of 622,712 to 35,369 copies per mL, and at 9 months was undetectable in 55% of the patients. Mean z scores for weight for age increased from a baseline of -1.61 to -1.12 at 12 months into therapy. CONCLUSIONS: A public health approach using 1 treatment regimen in generic form showed excellent efficacy among treatment-naive, HIV-infected children in a resource-limited country. Clinical and immunologic improvement occurred in all patients, but 9 months after the start of therapy, only 55% of the children had an undetectable viral load. PMID- 17846148 TI - Functionally specialized junctions between endothelial cells of lymphatic vessels. AB - Recirculation of fluid and cells through lymphatic vessels plays a key role in normal tissue homeostasis, inflammatory diseases, and cancer. Despite recent advances in understanding lymphatic function (Alitalo, K., T. Tammela, and T.V. Petrova. 2005. Nature. 438:946-953), the cellular features responsible for entry of fluid and cells into lymphatics are incompletely understood. We report the presence of novel junctions between endothelial cells of initial lymphatics at likely sites of fluid entry. Overlapping flaps at borders of oak leaf-shaped endothelial cells of initial lymphatics lacked junctions at the tip but were anchored on the sides by discontinuous button-like junctions (buttons) that differed from conventional, continuous, zipper-like junctions (zippers) in collecting lymphatics and blood vessels. However, both buttons and zippers were composed of vascular endothelial cadherin (VE-cadherin) and tight junction associated proteins, including occludin, claudin-5, zonula occludens-1, junctional adhesion molecule-A, and endothelial cell-selective adhesion molecule. In C57BL/6 mice, VE-cadherin was required for maintenance of junctional integrity, but platelet/endothelial cell adhesion molecule-1 was not. Growing tips of lymphatic sprouts had zippers, not buttons, suggesting that buttons are specialized junctions rather than immature ones. Our findings suggest that fluid enters throughout initial lymphatics via openings between buttons, which open and close without disrupting junctional integrity, but most leukocytes enter the proximal half of initial lymphatics. PMID- 17846149 TI - High basal STAT4 balanced by STAT1 induction to control type 1 interferon effects in natural killer cells. AB - The best-characterized type 1 interferon (IFN) signaling pathway depends on signal transducer and activator of transcription 1 (STAT1) and STAT2. The cytokines can, however, conditionally activate all STATs. Regulation of their access to particular signaling pathways is poorly understood. STAT4 is important for IFN-gamma induction, and NK cells are major producers of this cytokine. We report that NK cells have high basal STAT4 levels and sensitivity to type 1 IFN mediated STAT4 activation for IFN-gamma production. Increases in STAT1, driven during viral infection by either type 1 IFN or IFN-gamma, are associated with decreased STAT4 access. Both STAT1 and STAT2 are important for antiviral defense, but STAT1 has a unique role in protecting against sustained NK cell IFN-gamma production and resulting disease. The regulation occurs with an NK cell type 1 IFN receptor switch from a STAT4 to a STAT1 association. Thus, a fundamental characteristic of NK cells is high STAT4 bound to the type 1 IFN receptor. The conditions of infection result in STAT1 induction with displacement of STAT4. These studies elucidate the critical role of STAT4 levels in predisposing selection of specific signaling pathways, define the biological importance of regulation within particular cell lineages, and provide mechanistic insights for how this is accomplished in vivo. PMID- 17846151 TI - The orbital prefrontal cortex and drug addiction in laboratory animals and humans. AB - In this chapter, we review evidence implicating the orbitofrontal cortex (OFC) in drug addiction. We show that the orbital cortex is involved in conditioned reinforcement and is thereby important for the acquisition of cocaine-seeking behavior studied in a way that provides an animal experimental homologue of orbital cortex activation and craving upon exposure of addicts to drug-associated stimuli. We discuss the evidence indicating orbital prefrontal cortex dysfunction in human drug addicts, reviewing both neuropsychological and neuroimaging studies. Finally, we consider animal experimental evidence suggesting that addictive drugs may cause orbital cortex dysfunction and thereby contribute to the transition to drug addiction. Reconciling the observations that even brief periods of drug exposure can lead to long-lasting functional and structural deficits associated with the OFC together with those suggesting interactions between a vulnerable phenotype and chronic drug-self-administration will be an important topic of future research. PMID- 17846152 TI - Role of orbitofrontal cortex connections in emotion. AB - The orbitofrontal cortex is extensively connected with diverse neural areas that underlie its participation in emotional function. It receives extensive sensory input and sends output to areas important for emotional processing and expression, including medial temporal cortical areas, hypothalamic and brain stem autonomic areas, and the amygdala. In the rat, the functional relationship between the orbitofrontal cortex and amygdala has been investigated in numerous recent studies. Clearer understanding of the complex connections between the rat orbitofrontal cortex and the amygdala is fundamental to elucidating the functional contributions of these pathways. Recent work shows that, as in the primate, the subdivisions of the rat orbitofrontal cortex issue different patterns of projections to the amygdala, with intriguing variations in the relative distribution of projections to the sensory-related basal areas compared with output areas, such as the central nucleus. Notably, as has been observed in the monkey, the rat orbitofrontal cortex targets the intercalated nuclei, which contain GABAergic interneurons and provide local inhibitory influences within the amygdala. The complex connections between the orbitofrontal cortex and the amygdala, as well as other areas involved in emotion, suggest important implications for the role of the orbitofrontal cortex in anxiety disorders, in which emotional expression is not appropriate to the situation. PMID- 17846150 TI - Neurofascin as a novel target for autoantibody-mediated axonal injury. AB - Axonal injury is considered the major cause of disability in patients with multiple sclerosis (MS), but the underlying effector mechanisms are poorly understood. Starting with a proteomics-based approach, we identified neurofascin specific autoantibodies in patients with MS. These autoantibodies recognize the native form of the extracellular domains of both neurofascin 186 (NF186), a neuronal protein concentrated in myelinated fibers at nodes of Ranvier, and NF155, the oligodendrocyte-specific isoform of neurofascin. Our in vitro studies with hippocampal slice cultures indicate that neurofascin antibodies inhibit axonal conduction in a complement-dependent manner. To evaluate whether circulating antineurofascin antibodies mediate a pathogenic effect in vivo, we cotransferred these antibodies with myelin oligodendrocyte glycoprotein-specific encephalitogenic T cells to mimic the inflammatory pathology of MS and breach the blood-brain barrier. In this animal model, antibodies to neurofascin selectively targeted nodes of Ranvier, resulting in deposition of complement, axonal injury, and disease exacerbation. Collectively, these results identify a novel mechanism of immune-mediated axonal injury that can contribute to axonal pathology in MS. PMID- 17846153 TI - Keynote address: revaluing the orbital prefrontal cortex. AB - The importance of orbitofrontal cortex (OFC) in human behavioral regulation is no longer a matter of dispute, though its precise role remains a matter of ongoing investigation. It is ironic that this revaluation of OFC required a major departure from a historical nadir, during which it was viewed as redundant or "silent cortex," a situation that prevailed even up to the latter half of the 20th century. The increasing wealth of data from diverse fields within neuroscience now provides an unambiguous testament to the importance of this cortical region in behavioral regulation and cognition in general. PMID- 17846154 TI - Orbitofrontal cortex and amygdala contributions to affect and action in primates. AB - The amygdala and orbitofrontal cortex (OFC) work together as part of the neural circuitry guiding goal-directed behavior. This chapter explores the way in which the amygdala and OFC contribute to emotion and reward processing in macaque monkeys, taking into account recent methodological and conceptual advances. Although direct functional interaction of the amygdala and OFC is necessary for some types of stimulus-reward associations, it is not necessary for others. Both regions contribute to the expression of defensive responses to a potential predator. Contrary to the prevailing view, the amygdala and OFC make distinct contributions to emotional responses and reward processing. PMID- 17846155 TI - The role of the human orbitofrontal cortex in taste and flavor processing. AB - The human orbitofrontal cortex (OFC) plays an important role in representing taste, flavor, and food reward. The primary role of the OFC in taste is thought to be the encoding of affective value and the computation of perceived pleasantness. The OFC also encodes retronasal olfaction and oral somatosensation. During eating, distinct sensory inputs fuse into a unitary flavor percept, and there is evidence that this percept is encoded in the orbital cortex. Studies examining the effect of internal state on neural representation of food and drink further suggest that processing in the OFC is critical for representing the reward value of foods. Thus, it is likely that, in addition to serving as higher order gustatory cortex, the OFC integrates multiple sensory inputs and computes reward value to guide feeding behavior. PMID- 17846157 TI - What can an orbitofrontal cortex-endowed animal do with smells? AB - It is widely presumed that odor quality is a direct outcome of odorant molecular structure, but increasing evidence suggests that learning, experience, and context play important roles in human olfactory perception. Such data suggest that a given set of olfactory receptors activated by an odorant does not map directly onto a given odor percept. Rather, odor perception may rely on more synthetic, or integrative, mechanisms subserved by higher-order brain regions. Results presented here explore the specific role of human orbitofrontal cortex (OFC) in the formation and modulation of odor quality coding. Combining olfactory psychophysical techniques and functional imaging approaches, we have found that sensory-specific information about an odorant is not static or fixed within human olfactory OFC, but is highly malleable and can be rapidly updated by perceptual experience. Critically, the magnitude of OFC activation predicts subsequent behavioral improvement in olfactory perception. Our findings highlight the pivotal role of OFC in linking olfactory sensation, perception, and experience. It is worth considering that many of the current proposed functions attributed to the (distinctively mammalian) OFC are an extension of mechanisms that originally evolved to mediate response flexibility between chemosensory signals and appropriate behavioral actions. PMID- 17846156 TI - Neural correlates of inflexible behavior in the orbitofrontal-amygdalar circuit after cocaine exposure. AB - Addiction is characterized by compulsive or inflexible behavior, observed both in the context of drug-seeking and in contexts unrelated to drugs. One possible contributor to these inflexible behaviors may be drug-induced dysfunction within circuits that support behavioral flexibility, including the basolateral amygdala (ABL) and the orbitofrontal cortex (OFC). Here we describe data demonstrating that chronic cocaine exposure causes long-lasting changes in encoding properties in the ABL and the OFC during learning and reversal in an odor-guided task. In particular, these data suggest that inflexible encoding in ABL neurons may be the proximal cause of cocaine-induced behavioral inflexibility, and that a loss of outcome-expectant encoding in OFC neurons could be a more distal contributor to this impairment. A similar mechanism of drug-induced orbitofrontal-amygdalar dysfunction may cause inflexible behavior when animals and addicts are exposed to drug-associated cues and contexts. PMID- 17846158 TI - Neuronal mechanisms in prefrontal cortex underlying adaptive choice behavior. AB - This chapter aims to address two questions relating to the role of the prefrontal cortex (PFC) in reward-guided choice behavior. First, do PFC neurons encode rewards per se, or are they encoding behavioral sequelae of reward? To address this, we recorded simultaneously from multiple PFC subregions, with the rationale that neuronal selectivity that directly encoded the reward outcome should occur before selectivity that reflected reward-related sequelae. Our results indicate that neurons in the orbitofrontal cortex (OFC) encode reward information before neurons in the dorsolateral PFC (DLPFC). Furthermore, whereas DLPFC neurons encoded both the upcoming response as well as the expected reward, OFC neurons encoded the reward alone. Our interpretation of these results is that the OFC encodes the reward and passes this information to the DLPFC, which uses it to determine the behavioral response. The second question is whether the encoding is specific to the reward outcome or reflective of a more abstract value signal that could facilitate decision making. We examined this by determining whether the PFC encodes other types of information relevant to decision making, such as probability of success and effort. We found that many PFC neurons encoded at least one of these variables, but neurons in the OFC and the medial PFC (MPFC) encoded combinations of the variables indicative of encoding an abstract value signal. This signal could provide decision making with flexibility and a capacity to deal with novelty, which are two of the hallmark features of prefrontal function. Future research will focus on delineating the differential contributions of the OFC and the MPFC to decision making. PMID- 17846159 TI - Vulnerability of the orbitofrontal cortex to age-associated structural and functional brain changes. AB - Cross-sectional and longitudinal findings from the Baltimore Longitudinal Study of Aging (BLSA) neuroimaging study indicate that the orbitofrontal cortex (OFC) is among those regions vulnerable to age-associated tissue loss in older adults without dementia. Neuropathologic and recent in vivo amyloid imaging studies indicate that the OFC is also among the earliest neocortical regions to show deposition of amyloid plaques in aging and Alzheimer's disease. We performed behavioral and imaging studies to investigate age effects on specific aspects of OFC function. We compared performance in young (age 20-40) and old (age 60 and older) adults on cognitive tasks selected for differential sensitivity to OFC versus dorsolateral prefrontal cortex (DLPFC). Overall, greater age differences were seen in the OFC tasks compared to DLPFC tasks, with Delayed Match and Non Match to Sample tasks showing the greatest effect size among OFC tasks and Self Ordered Pointing Task showing the greatest effect size among DLPFC tasks. A functional magnetic resonance imaging study was conducted in parallel to probe the neural underpinnings of age differences in OFC function using the Delayed Match and Non-Match to Sample paradigm. Young but not old adults showed the expected OFC activation. Older compared with young adults showed greater activation in association with successful performance for several posterior regions, perhaps indicating compensation in the face of OFC deficits. Together, these findings indicate a vulnerability of the OFC to age-related decline in brain structure and function. Future studies using new in vivo imaging probes will help determine whether neuropathologic changes underlie the structural and functional changes. PMID- 17846160 TI - Neuronal activity related to anticipated reward in frontal cortex: does it represent value or reflect motivation? AB - It is thought that neuronal activity in orbitofrontal cortex (OFC) represents the value of anticipated reward; however activity in many other brain areas also seems to reflect expected reward value. For example, we have shown that in monkeys performing a memory-guided saccade task for a reward of variable size, activity in numerous areas of frontal cortex is stronger when the monkey anticipates a larger reward. The activity of these neurons might be related to the value of the expected reward or to the degree of motivation induced by expectation of the reward. Anticipation of a more valued reward leads to stronger motivation, as evidenced by measures of arousal, attention, and intensity of motor output. On the assumption that motivated behavior depends on influences arising in the limbic system and acting on the motor system, we hypothesized that neuronal signals representing reward value are unique to OFC, whereas signals arising from other frontal areas, those more closely tied the motor system, reflect the degree of motivation. To test this hypothesis, we recorded from single neurons in OFC and premotor cortex while two monkeys performed a task in which we dissociated value from motivation. Neuronal activity in premotor cortex reflected the monkey's degree of motivation, presumably related to the monkey's level of motor readiness and movement preparation, whereas neuronal activity in OFC represented the value of expected reward. PMID- 17846161 TI - The role of orbitofrontal cortex in decision making: a component process account. AB - Clinical accounts of the effects of damage to orbitofrontal cortex (OFC) have provided important clues about the functions of this region in humans. Patients with OFC injury can demonstrate relatively isolated difficulties with decision making, and the development of laboratory tasks that captured these difficulties was an important advance. However, much of the work to date has been limited by the use of a single, complex decision-making task and by a narrow focus on risky decisions. A fuller understanding of the neural basis of decision making requires identification of the simpler components that underlie this complex behavior. Here, I review evidence that OFC lesions disrupt reversal learning in humans, as in animals, and show that this deficit in reversal learning is an important mechanism underlying the difficulties of such patients in the Iowa gambling task. Reversal learning, in turn, can be decomposed into simpler processes: a failure to rapidly learn from negative feedback may be the critical difficulty for OFC patients. OFC damage can also affect forms of decision making that do not require trial-by-trial learning. Preference judgment is a simple form of decision making that requires comparing the relative value of options. Humans with OFC lesions are more inconsistent in their choices, even in very simple preference judgment tasks. These results are broadly consistent with the view that OFC is critically involved in representing the relative value of stimuli, but also raise the possibility that this region plays distinct roles in reinforcement learning and value-based judgment. PMID- 17846162 TI - The orbitofrontal cortex, impulsivity, and addiction: probing orbitofrontal dysfunction at the neural, neurochemical, and molecular level. AB - The association between impulsivity and addiction is currently a topic of intense research interest. Investigations into the neurobiological basis of aspects of impulse control have revealed some striking parallels between the brain circuitry and neurochemical systems implicated in drug dependence and impulsive behavior. Both processes are heavily regulated by limbic corticostriatal circuits including the orbitofrontal cortex (OFC) and nucleus accumbens (NAC), and are modulated by dopamine (DA) and serotonin (5-HT). Hypoactivity within the OFC has been observed in recently abstinent cocaine users, and this is thought to contribute to the cognitive deficits associated with drug abuse, including impairments in impulse control. However, the neurobiological mechanisms underlying these functional and behavioral deficits are unclear. In parallel to observations made in the NAC, recent data indicate that chronic cocaine use also induces the transcription factor DeltaFosB in the OFC and that this plays a role in the cognitive sequelae of chronic cocaine administration. In particular, DeltaFosB appears to be involved in the development of tolerance to the disruptive effects of acute cocaine on impulsivity and motivation observed after repeated cocaine administration. Increased DeltaFosB also contributes to increased impulsivity during withdrawal from the drug. Both effects could be attributed to the up regulation of local inhibitory processes in the OFC after over-expression of DeltaFosB and chronic cocaine treatment. Through integrating what is known of the interaction between addictive drugs and impulsivity at the neural, neurochemical, and molecular level, novel insight may be obtained into the multi-faceted regulation of the addicted state. PMID- 17846163 TI - Symptoms of frontotemporal dementia provide insights into orbitofrontal cortex function and social behavior. AB - Recent investigations into the brain substrates of behavioral changes in frontotemporal dementia (FTD) demonstrate that the orbitofrontal cortex (OFC) plays a crucial role in normal social and emotional behavior. The initial symptoms of FTD reflect the early involvement of OFC as well as the disruption of an associated network involving the insula, striatum, and medial frontal lobes. As predicted by patients with other types of OFC lesions, FTD patients show impairments involving stimulus-reward reversal learning, response inhibition, and ability to judge the appropriateness of their behavior in the social context. While the natural reward system remains intact in these patients, that is, patients will seek out directly rewarding stimuli, such as food and sex, with progressive OFC dysfunction they lose the ability to process complex stimulus reward contingencies. These abnormalities are apparent in their social interactions, which break down early in the disease. Also, deficits in emotion recognition and empathy have been directly linked to OFC atrophy in these patients. In contrast, some patients with early FTD show intact cognitive skills, including memory and executive functioning. Here, we review the behavioral and neuropsychological changes that accompany OFC atrophy in FTD and argue that phylogenetically new neurons found in this region, called von Economo neurons, are selectively vulnerable in FTD. PMID- 17846164 TI - The mechanism of fast-gate opening in ClC-0. AB - ClC-0 is a chloride channel whose gating is sensitive to both voltage and chloride. Based on analysis of gating kinetics using single-channel recordings, a five-state model was proposed to describe the dependence of ClC-0 fast-gate opening on voltage and external chloride (Chen, T.-Y., and C. Miller. 1996. J. Gen. Physiol. 108:237-250). We aimed to use this five-state model as a starting point for understanding the structural changes that occur during gating. Using macroscopic patch recordings, we were able to reproduce the effects of voltage and chloride that were reported by Chen and Miller and to fit our opening rate constant data to the five-state model. Upon further analysis of both our data and those of Chen and Miller, we learned that in contrast to their conclusions, (a) the features in the data are not adequate to rule out a simpler four-state model, and (b) the chloride-binding step is voltage dependent. In order to be able to evaluate the effects of mutants on gating (described in the companion paper, see Engh et al. on p. 351 of this issue), we developed a method for determining the error on gating model parameters, and evaluated the sources of this error. To begin to mesh the kinetic model(s) with the known CLC structures, a model of ClC 0 was generated computationally based on the X-ray crystal structure of the prokaryotic homolog ClC-ec1. Analysis of pore electrostatics in this homology model suggests that at least two of the conclusions derived from the gating kinetics analysis are consistent with the known CLC structures: (1) chloride binding is necessary for channel opening, and (2) chloride binding to any of the three known chloride-binding sites must be voltage dependent. PMID- 17846165 TI - The role of a conserved lysine in chloride- and voltage-dependent ClC-0 fast gating. AB - ClC-0 is a chloride channel whose gating is sensitive to voltage, chloride, and pH. In a previous publication, we showed that the K149C mutation causes a +70-mV shift in the voltage dependence of ClC-0 fast gating. In this paper we analyze the effects of a series of mutations at K149 on the voltage and chloride dependence of gating. By fitting our data to the previously proposed four-state model for ClC-0 fast gating, we show which steps in fast-gate opening are likely to be affected by these mutations. Computational analysis of mutant ClC-0 homology models show electrostatic contributions to chloride binding that may partially account for the effects of K149 on gating. The analysis of gating kinetics in combination with the available structural information suggests some of the structural changes likely to underpin fast-gate opening. PMID- 17846167 TI - Jidong Liu: probing P-bodies for the secrets of silencing. Interview by Ruth Williams. AB - Jidong Liu tackles the many unanswered questions of RNAi. PMID- 17846166 TI - Triadin binding to the C-terminal luminal loop of the ryanodine receptor is important for skeletal muscle excitation contraction coupling. AB - Ca(2+) release from intracellular stores is controlled by complex interactions between multiple proteins. Triadin is a transmembrane glycoprotein of the junctional sarcoplasmic reticulum of striated muscle that interacts with both calsequestrin and the type 1 ryanodine receptor (RyR1) to communicate changes in luminal Ca(2+) to the release machinery. However, the potential impact of the triadin association with RyR1 in skeletal muscle excitation-contraction coupling remains elusive. Here we show that triadin binding to RyR1 is critically important for rapid Ca(2+) release during excitation-contraction coupling. To assess the functional impact of the triadin-RyR1 interaction, we expressed RyR1 mutants in which one or more of three negatively charged residues (D4878, D4907, and E4908) in the terminal RyR1 intraluminal loop were mutated to alanines in RyR1-null (dyspedic) myotubes. Coimmunoprecipitation revealed that triadin, but not junctin, binding to RyR1 was abolished in the triple (D4878A/D4907A/E4908A) mutant and one of the double (D4907A/E4908A) mutants, partially reduced in the D4878A/D4907A double mutant, but not affected by either individual (D4878A, D4907A, E4908A) mutations or the D4878A/E4908A double mutation. Functional studies revealed that the rate of voltage- and ligand-gated SR Ca(2+) release were reduced in proportion to the degree of interruption in triadin binding. Ryanodine binding, single channel recording, and calcium release experiments conducted on WT and triple mutant channels in the absence of triadin demonstrated that the luminal loop mutations do not directly alter RyR1 function. These findings demonstrate that junctin and triadin bind to different sites on RyR1 and that triadin plays an important role in ensuring rapid Ca(2+) release during excitation-contraction coupling in skeletal muscle. PMID- 17846168 TI - Suv4-20h deficiency results in telomere elongation and derepression of telomere recombination. AB - Mammalian telomeres have heterochromatic features, including trimethylated histone H3 at lysine 9 (H3K9me3) and trimethylated histone H4 at lysine 20 (H4K20me3). In addition, subtelomeric DNA is hypermethylated. The enzymatic activities responsible for these modifications at telomeres are beginning to be characterized. In particular, H4K20me3 at telomeres could be catalyzed by the novel Suv4-20h1 and Suv4-20h2 histone methyltransferases (HMTases). In this study, we demonstrate that the Suv4-20h enzymes are responsible for this histone modification at telomeres. Cells deficient for Suv4-20h2 or for both Suv4-20h1 and Suv4-20h2 show decreased levels of H4K20me3 at telomeres and subtelomeres in the absence of changes in H3K9me3. These epigenetic alterations are accompanied by telomere elongation, indicating a role for Suv4-20h HMTases in telomere length control. Finally, cells lacking either the Suv4-20h or Suv39h HMTases show increased frequencies of telomere recombination in the absence of changes in subtelomeric DNA methylation. These results demonstrate the importance of chromatin architecture in the maintenance of telomere length homeostasis and reveal a novel role for histone lysine methylation in controlling telomere recombination. PMID- 17846169 TI - Splicing-independent recruitment of spliceosomal small nuclear RNPs to nascent RNA polymerase II transcripts. AB - In amphibian oocytes, most lateral loops of the lampbrush chromosomes correspond to active transcriptional sites for RNA polymerase II. We show that newly assembled small nuclear ribonucleoprotein (RNP [snRNP]) particles, which are formed upon cytoplasmic injection of fluorescently labeled spliceosomal small nuclear RNAs (snRNAs), target the nascent transcripts of the chromosomal loops. With this new targeting assay, we demonstrate that nonfunctional forms of U1 and U2 snRNAs still associate with the active transcriptional units. In particular, we find that their association with nascent RNP fibrils is independent of their base pairing with pre-messenger RNAs. Additionally, stem loop I of the U1 snRNA is identified as a discrete domain that is both necessary and sufficient for association with nascent transcripts. Finally, in oocytes deficient in splicing, the recruitment of U1, U4, and U5 snRNPs to transcriptional units is not affected. Collectively, these data indicate that the recruitment of snRNPs to nascent transcripts and the assembly of the spliceosome are uncoupled events. PMID- 17846170 TI - Defining early steps in mRNA transport: mutant mRNA in myotonic dystrophy type I is blocked at entry into SC-35 domains. AB - In myotonic dystrophy type 1 (DM1), triplet repeat expansion in the 3' untranslated region of dystrophia myotonica protein kinase (DMPK) causes the nuclear retention of mutant messenger RNA (mRNA). Although the DMPK gene locus positions precisely at the outer edge of a factor-rich SC-35 domain, the normal mRNA consistently accumulates within the domain, and this RNA is depleted upon transcriptional inhibition. In DM1, mutant transcripts detach from the gene but accumulate in granules that abut but do not enter SC-35 domains, suggesting that RNA entry into the domain is blocked. Despite their exclusion from these compartments, mutant transcripts are spliced. MBNL1 (muscleblind-like protein 1) is an alternative splicing factor that becomes highly concentrated with mutant RNA foci. Small interfering RNA-mediated knockdown of MBNL1 promotes the accumulation or entry of newly synthesized mutant transcripts in the SC-35 domain. Collectively, these data suggest that an initial step in the intranuclear path of some mRNAs is passage from the gene into an SC-35 domain and implicate these structures in postsplicing steps before export. PMID- 17846171 TI - A novel role for IGF-1R in p53-mediated apoptosis through translational modulation of the p53-Mdm2 feedback loop. AB - Insulin-like growth factor 1 receptor (IGF-1R) is important in cancer cell growth and survival and has been implicated in cancer pathophysiology and treatment. Here we report a novel function for IGF-1R in p53-dependent apoptotic response. We show that inhibition or loss of IGF-1R activity reduces translational synthesis of p53 and Mdm2 protein. Notably, IGF-1R inhibition increases p53 protein stability by reducing p53 ubiquitination and maintains p53 at low levels by decreasing p53 synthesis, thus rendering p53 insensitive to stabilization after DNA damage. The accumulation and apoptosis of DNA-damage-induced p53 is therefore reduced in Igf-1r(-/-) mouse embryonic fibroblasts or tumor cells treated with the IGF-1R inhibitor. Furthermore, we find that inhibition of IGF-1R reduces p53 and Mdm2 translation through a gene-specific mechanism mediated by the respective 5' untranslated region of p53 and mdm2 messenger RNA. The eukaryotic translation initiation factor 4F complex is also involved in this translational inhibition. These results demonstrate an unexpected role for translational control by IGF-1R in p53-mediated apoptosis. PMID- 17846172 TI - SAG/ROC2 E3 ligase regulates skin carcinogenesis by stage-dependent targeting of c-Jun/AP1 and IkappaB-alpha/NF-kappaB. AB - Sensitive to apoptosis gene (SAG)/regulator of cullins-2-Skp1-cullin-F-box protein (SCF) E3 ubiquitin ligase regulates cellular functions through ubiquitination and degradation of protein substrates. We report that, when expressed in mouse epidermis driven by the K14 promoter, SAG inhibited TPA induced c-Jun levels and activator protein-1 (AP-1) activity in both in vitro primary culture, in vivo transgenic mice, and an AP-1- luciferase reporter mouse model. After AP-1 inactivation, epidermal proliferation induced by 7,12 dimethylbenz(a)-anthracene/12-O-tetradecanoylphorbol-13-acetate at the early stage of carcinogenesis was substantially inhibited. Later stage tumor formation was also substantially inhibited with prolonged latency and reduced frequency of tumor formation. Interestingly, SAG expression increased tumor size, not because of accelerated proliferation, but caused by reduced apoptosis resulting, at least in part, from nuclear factor kappaB (NF-kappaB) activation. Thus, SAG, in a manner depending on the availability of F-box proteins, demonstrated early-stage suppression of tumor formation by promoting c-Jun degradation, thereby inhibiting AP-1, and later-stage enhancement of tumor growth, by promoting inhibitor of kappaBalpha degradation to activate NF-kappaB and inhibit apoptosis. PMID- 17846173 TI - Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6. AB - Sequestration of misfolded proteins into pericentriolar inclusions called aggresomes is a means that cells use to minimize misfolded protein-induced cytotoxicity. However, the molecular mechanism by which misfolded proteins are recruited to aggresomes remains unclear. Mutations in the E3 ligase parkin cause autosomal recessive Parkinson's disease that is devoid of Lewy bodies, which are similar to aggresomes. Here, we report that parkin cooperates with heterodimeric E2 enzyme UbcH13/Uev1a to mediate K63-linked polyubiquitination of misfolded DJ 1. K63-linked polyubiquitination of misfolded DJ-1 serves as a signal for interaction with histone deacetylase 6, an adaptor protein that binds the dynein dynactin complex. Through this interaction, misfolded DJ-1 is linked to the dynein motor and transported to aggresomes. Furthermore, fibroblasts lacking parkin display deficits in targeting misfolded DJ-1 to aggresomes. Our findings reveal a signaling role for K63-linked polyubiquitination in dynein-mediated transport, identify parkin as a key regulator in the recruitment of misfolded DJ 1 to aggresomes, and have important implications regarding the biogenesis of Lewy bodies. PMID- 17846174 TI - Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2(-/-) mice. AB - The protein tyrosine kinase Pyk2 is highly expressed in osteoclasts, where it is primarily localized in podosomes. Deletion of Pyk2 in mice leads to mild osteopetrosis due to impairment in osteoclast function. Pyk2-null osteoclasts were unable to transform podosome clusters into a podosome belt at the cell periphery; instead of a sealing zone only small actin rings were formed, resulting in impaired bone resorption. Furthermore, in Pyk2-null osteoclasts, Rho activity was enhanced while microtubule acetylation and stability were significantly reduced. Rescue experiments by ectopic expression of wild-type or a variety of Pyk2 mutants in osteoclasts from Pyk2(-/-) mice have shown that the FAT domain of Pyk2 is essential for podosome belt and sealing zone formation as well as for bone resorption. These experiments underscore an important role of Pyk2 in microtubule-dependent podosome organization, bone resorption, and other osteoclast functions. PMID- 17846177 TI - Conflict on the courts: a review of sports-related violence literature. AB - Sports-related violence is a form of interpersonal violence. Violence that occurs in and around the sporting world can have potentially severe physical and psychological repercussions for those involved. Although scholars in a wide range of disciplines have addressed three of the subsets of sports-related violence, they have done so without regard to the interconnected nature of the subsets, choosing instead to look at hazing, brawling, and foul play as independent problems. By separating hazing, brawling, and foul play and failing to recognize that their connection to sport connects them, scholars fail to see how sports related violence is a broad example of interpersonal violence. This review describes some of the academic literature, primarily from the United States, and identifies similar themes and prevention suggestions that appear across disciplines. It also argues that the three subsets are an interconnected whole of sports-related violence that deserves more detailed study. PMID- 17846175 TI - Katanin regulates dynamics of microtubules and biogenesis of motile cilia. AB - The in vivo significance of microtubule severing and the mechanisms governing its spatial regulation are not well understood. In Tetrahymena, a cell type with elaborate microtubule arrays, we engineered null mutations in subunits of the microtubule-severing complex, katanin. We show that katanin activity is essential. The net effect of katanin on the polymer mass depends on the microtubule type and location. Although katanin reduces the polymer mass and destabilizes the internal network of microtubules, its activity increases the mass of ciliary microtubules. We also show that katanin reduces the levels of several types of post-translational modifications on tubulin of internal and cortical microtubules. Furthermore, katanin deficiencies phenocopy a mutation of beta-tubulin that prevents deposition of polymodifications (glutamylation and glycylation) on microtubules. We propose that katanin preferentially severs older, post-translationally modified segments of microtubules. PMID- 17846176 TI - Kinesin-5 regulates the growth of the axon by acting as a brake on its microtubule array. AB - Kinesin-5 is a homotetrameric motor protein that interacts with adjacent microtubules in the mitotic spindle. Kinesin-5 is also highly expressed in developing postmitotic neurons. Axons of cultured neurons experimentally depleted of kinesin-5 grow up to five times longer than controls and display more branches. The faster growth rates are accompanied by a doubling of the frequency of transport of short microtubules, suggesting a major role for kinesin-5 in the balance of motor-driven forces on the axonal microtubule array. Live-cell imaging reveals that the effects on axonal length of kinesin-5 depletion are caused partly by a lower propensity of the axon and newly forming branches to undergo bouts of retraction. Overexpression of wild-type kinesin-5, but not a rigor mutant of kinesin-5, has the inverse effect on axonal length. These results indicate that kinesin-5 imposes restrictions on the growth of the axon and does so at least in part by generating forces on the axonal microtubule array. PMID- 17846178 TI - Homicides and intimate partner violence: a literature review. AB - The purpose of this article is to examine the literature on intimate partner homicides (IPH). The review begins by describing the factors, magnitude, and consequences associated with IPH, focusing on studies from the United States. Second, the article discusses the public health implications of preventing IPH and the limitations associated with the IPH literature. Last, the article concludes with recommendations of IPH in terms of practice, policy, and research. PMID- 17846179 TI - Trauma among female veterans: a critical review. AB - This article reviews the literature documenting the nature and prevalence of traumatic experiences, trauma-related mental and physical health problems, and service use among female veterans. Existing research indicates that female veterans experience higher rates of trauma exposure in comparison to the general population. Emerging data also suggest that female veterans may be as likely to be exposed to combat as male veterans, although not as directly or as frequently. Female veterans also report high rates of posttraumatic stress disorder, which has been associated with poor psychiatric and physical functioning. Although sexual assault history has been related to increased medical service use, further research is needed to understand relationships between trauma history and patterns of medical and mental health service use. Researchers also are encouraged to employ standardized definitions of trauma and to investigate new areas, such as treatment outcomes and mediators of trauma and health. Policy and practice implications are discussed. PMID- 17846180 TI - Resistance, reluctance, and readiness in perpetrators of abuse against women and children. AB - Perpetrators of abuse and violence against women and children are often reluctant participants in intervention programs. They frequently fail to attend scheduled appointments, are sometimes openly hostile to intervention staff, and often judge program materials as irrelevant to their situation. Recognizing this problem, researchers and practitioners have begun to develop models and tools to more appropriately assess and intervene with reluctant clients. Unfortunately, the resulting proliferation and inconsistent application of terms and theories have led to considerable confusion in characterizing reluctant clients and have significantly hampered research on strategies that may be helpful to better meet the needs of this client group. The purpose of this review is to help standardize the definition and measurement of treatment reluctance as it applies to violence perpetration and to review evidence for the importance of these aspects of client reluctance to intervention. Recommendations for assessing reluctance in research and clinical practice are also provided. PMID- 17846183 TI - Metabolite findings in tumefactive demyelinating lesions utilizing short echo time proton magnetic resonance spectroscopy. PMID- 17846184 TI - The vascular plug: a new device for parent artery occlusion. PMID- 17846185 TI - Fate of submitted manuscripts rejected from the American Journal of Neuroradiology: outcomes and commentary. AB - BACKGROUND AND PURPOSE: The purpose of this study was to determine the publication fate of submissions previously rejected from the American Journal of Neuroradiology (AJNR) to provide guidance to authors who receive rejection notices. MATERIALS AND METHODS: A retrospective search by using MEDLINE of all submissions rejected from AJNR in 2004 was performed to identify subsequently published manuscripts. The fate of subsequently published manuscripts was analyzed as a function of submission type (major study, technical note, or case report), publication delay, publishing journal type (neuroradiology, general radiology, or clinical neuroscience journal), impact factor, publication volume, and circulation volume. RESULTS: Of the 554 rejected submissions to AJNR, 315 (56%) were subsequently published in 115 different journals, with the journal Neuroradiology publishing the greatest number of articles (37 [12%] of 315). The mean publication delay was 15.8 +/- 7.5 months. Major studies were more likely than case reports to be subsequently published (P = .034), but all 3 subtypes were published at rates greater than 50%. Radiologic journals collectively published approximately 60% of subsequent publications, whereas neurosurgery and neurology journals published 27% of rejected manuscripts. The mean impact factor of journals subsequently publishing rejected manuscripts was 1.8 +/- 1.3 (AJNR = 2.5), and 24 (7.5%) manuscripts were subsequently published in journals with higher impact factors than AJNR. CONCLUSIONS: These findings should give hope to authors receiving a rejection from AJNR, because greater than 50% of articles rejected from AJNR are subsequently published within 2-3 years, irrespective of publication type, into high-quality journals. PMID- 17846186 TI - Performance measures in neuroradiology. AB - Performance measurement has been added to the Medicare payment scheme as of July 2007. Two performance measures are applicable to neuroradiology, pertaining to brain and vascular imaging in stroke. These measures are early attempts to rigorously define the meaning of effective performance of neuroradiology. PMID- 17846187 TI - Position statement on percutaneous vertebral augmentation: a consensus statement developed by the American Society of Interventional and Therapeutic Neuroradiology, Society of Interventional Radiology, American Association of Neurological Surgeons/Congress of Neurological Surgeons, and American Society of Spine Radiology. PMID- 17846188 TI - Comparison of low-dose with standard-dose multidetector CT in cervical spine trauma. AB - BACKGROUND AND PURPOSE: The purpose of this work was to evaluate the possible use of low-dose multidetector CT (MDCT) in cervical clearance of patients with blunt trauma. MATERIALS AND METHODS: A total of 191 patients underwent cervical spine MDCT with 6- and 16-MDCT: standard-dose (n = 51) and low-dose MDCT with tube current modulation at high (n = 70) and low (n = 70) tube voltage (kilovolts). Effective dose, image noise, and subjective image quality were calculated in all of the patients. RESULTS: MDCT found 18 patients (9.4%) with a cervical spine fracture, 3 in the standard-dose and 15 in the low-dose group, 14 of them with unstable lesions. Tube current modulation reduced the dose by 50%-61% in all of the low-dose examinations. The mean effective dose was 3.75, 1.57, and 1.08 mSv, and mean image noise was 14.82, 17.46, and 19.72 Hounsfield units for standard dose and low dose with high and low kilovolt examinations, respectively. These differences in mean effective dose and image noise were significant between the 3 examination groups (Kruskal-Wallis test: P < .0001 and P = .0001). Evaluation of subjective image quality by 2 radiologists and 2 residents showed no significant difference in image quality score among the 3 examination groups (Kruskal-Wallis tests, P = .61, .32, .18, and .31). All of the reviewers correctly detected 18 fractures, except 1 resident, who missed 3 fractures. CONCLUSION: Low-dose cervical spine MDCT in patients with blunt trauma gives a substantial dose reduction of 61%-71%, compared with standard-dose MDCT, with a small increase in image noise and without difference in subjective image quality evaluation. PMID- 17846189 TI - CT fluoroscopically guided percutaneous placement of transiliosacral rod for sacral insufficiency fracture: case report and technique. AB - Treatment of sacral insufficiency fractures (SIFs) has traditionally been conservative, but several patients have been treated with percutaneous sacroplasty. Unfortunately, in the setting of severe, bilateral SIFs, cement may not withstand shear forces present at the lumbosacral junction, and surgical hardware may not provide adequate fixation in osteoporotic, cancellous bone of the sacrum, leading to eventual pseudarthrosis. Thus, we propose a novel technique in which guidance with CT fluoroscopy allows placement of a transiliosacral bar in conjunction with sacroplasty. PMID- 17846190 TI - Analysis of metabolic indices in regions of abnormal perfusion in patients with high-grade glioma. AB - BACKGROUND AND PURPOSE: MR spectroscopic imaging (MRSI) and dynamic susceptibility-contrast MR imaging (DSC-MR imaging) are functional in vivo techniques for assessing tumor metabolism and vasculature characteristics. Because tumor hypoxia is influenced by tortuous, degraded, swollen, and angiogenic tumor vasculature, regions of abnormal perfusion parameters should coexist with changes in lactate and creatine metabolite levels. MATERIALS AND METHODS: DSC-MR imaging and lactate-edited MRSI were performed on 38 treatment naive patients with high-grade gliomas (17 grade III, 21 grade IV) before surgical diagnosis. Regions of abnormal perfusion were determined from peak height and percent recovery maps for each voxel within the spectroscopic imaging volume. Choline, creatine, and lactate levels within voxels experiencing only abnormal peak height (aPH), only abnormal recovery (aRec), and both abnormal peak height and recovery (aPH+aRec) were determined and compared to the surrounding T2 hyperintensity (T2h) and normal-appearing white matter. RESULTS: There were decreasing trends in volume from aPH to aRec to aPH+aRec regions for both grade III and grade IV gliomas. Grade IV gliomas exhibited significantly elevated choline in all abnormal perfusion regions, with reduced creatine and increased lactate in the aRec region relative to the surrounding T2h. Grade III gliomas showed trends toward increased creatine within the aPH region and reduced levels within the aRec region. CONCLUSION: Depressed creatine and elevated lactate levels confirmed the lack of oxygenation within regions of compromised vascular integrity. Identification of regions with leaky or dense vasculature and metabolic markers of hypoxia and cellular proliferation could be useful in determining the more aggressive part of the tumor for targeting, monitoring, and assessing effects of treatment. PMID- 17846191 TI - Rhabdoid meningioma: clinical features and MR imaging findings in 15 patients. AB - BACKGROUND AND PURPOSE: Rhabdoid meningioma (RM) is a recently described variant of malignant meningioma, with radiologic features currently not well characterized in the medical literature. The purpose of this study was to describe and characterize clinical features and imaging findings associated with RM. MATERIALS AND METHODS: CT (n = 8) and MR (n = 15) images of 15 patients (4 men and 11 women; mean age, 52 years; range, 22-75 years) with 16 pathologically proved RMs along with associated clinical records were retrospectively reviewed. All of the patients underwent surgical resection and had additional radiation therapy except for 1 patient. After surgery, the patients had follow-up brain MR imaging to evaluate for tumor recurrence. RESULTS: Nine lesions (56%) were located in the cerebral convexity, and 4 lesions (25%) were located in the parasagittal areas. The tumors were isointense (n = 15) to gray matter on T1 weighted images, whereas they were hyperintense (n = 14) on T2-weighted images. On gadolinium-enhanced T1-weighted images, homogeneous enhancement was seen in 10 lesions, and heterogeneous enhancement was seen in 6 lesions that had cysts. Cystic components were noted in 6 lesions (38%). Severe peritumoral edema was seen in 12 lesions (75%). Nine lesions (56%) had hyperostosis, and 5 of them also had bone destruction. Among the 8 cases with initial CT scans, only 1 had amorphous calcifications (13%). There was only 1 recurrence of RM found during the follow-up period after surgical resection. CONCLUSION: RMs tend to have prominent peritumoral edema, cystic components, and bone involvement. PMID- 17846192 TI - Intracranial solitary fibrous tumors: imaging findings in 6 consecutive patients. AB - BACKGROUND AND PURPOSE: Intracranial solitary fibrous tumors (ISFTs) are rare mesenchymal neoplasms originating in the meninges. The aim of this study was to describe the CT, MR imaging, and angiographic features of the solitary fibrous tumor and to identify imaging characteristics. MATERIALS AND METHODS: We retrospectively reviewed CT, MR, and angiographic findings in 6 cases of ISFT. We evaluated the size, shape, and location of the tumor; the internal content and margin of the lesion; the pattern of enhancement; and the change of the adjacent structures. Density on noncontrast CT scans, signal intensity on MR images, and angiographic features were also documented. RESULTS: Each lesion appeared as a discrete extra-axial mass (size, 3-7 cm; mean, 5 cm). Five lesions were entirely solid, and 1 had peritumoral cyst. All 5 of the noncontrast CT scans showed hyperattenuated masses, and the tumors exhibited marked heterogeneous enhancement. No lesion contained calcification, and 2 cases showed bone invasions. On the MR images, 4 lesions showed mixed signal intensity on T2 weighted imaging. All of the lesions revealed marked heterogeneous enhancement. All of the tumors had thickening of the meninges adjacent to the tumor. Angiography showed delayed tumor blushing in all, and 3 of them had dysplastic dilation of the tumor vessels. CONCLUSION: Although there are no pathognomonic imaging findings, some imaging features, such as the "black-and-white mixed" pattern on T2-weighted images and marked heterogeneous enhancement, might be helpful in the diagnosis of intracranial solitary fibrous tumor. PMID- 17846193 TI - Regional cerebral blood flow using quantitative MR angiography. AB - BACKGROUND AND PURPOSE: We sought to derive regional cerebral blood flow using vessel flows from quantitative MR angiography (qMRA). MATERIALS AND METHODS: Flow rates in the 15 major cerebral arteries were measured on retrospectively gated fast 2D phase-contrast MR angiography obtained in 83 healthy adult volunteers (age range, 24-74 years; mean, 42 years). The arterial network of the brain was partitioned into 12 different regions, in which flows were calculated from the measured flows of the 15 cerebral arteries. RESULTS: The mean flows of the 15 arteries and the 12 regions were calculated. The mean total cranial flow and the mean total cerebral blood flow were 949 +/- 158 mL/min and 695 +/- 113 mL/min, respectively. The mean regional flows for the anterior and posterior circulation were 483 +/- 87 mL/min and 212 +/- 34 mL/min, respectively. The relative contributions of the flows in the 11 regions to their parent regions were obtained. The mean flows in the individual arteries and the regions with age were also calculated. The mean flows for the female group were significantly lower than those for the male group (P < .001) for the 2 common carotids and the cranial circulation and left/right extracranial circulation. However, the intracranial circulation was not different between sexes. CONCLUSIONS: The 12 regions in the cerebral circulation were identified and formed into a partition tree, and the mean regional flow for each region was determined using vessel flows from qMRA. PMID- 17846194 TI - A preliminary study revealing a new association in patients undergoing maintenance hemodialysis: manganism symptoms and T1 hyperintense changes in the basal ganglia. AB - BACKGROUND AND PURPOSE: Patients undergoing parenteral nutrition and those with portosystemic encephalopathy secondary to chronic liver disease and acquired and congenital portosystemic venous shunts frequently present manganese deposition in the basal ganglia, detected by MR imaging as hyperintense areas on T1-weighted sequences. We also observed similar abnormalities in the basal ganglia of patients with chronic renal failure undergoing maintenance hemodialysis. Our aim was to evaluate the pallidal signal intensity on T1-weighted images in a series of patients undergoing hemodialysis, with further evaluation of serum manganese levels and neurologic correlation, comparing them with patients with chronic renal failure without dialytic treatment. MATERIALS AND METHODS: We performed MR imaging examinations in 9 patients with chronic renal failure, 5 of whom were undergoing hemodialysis. An experienced neuroradiologist scrutinized the presence of symmetric hyperintensities in the basal ganglia on T1-weighted sequences. We also determined the serum manganese levels and performed the neurologic evaluations in all patients. RESULTS: All patients undergoing hemodialysis presented elevated serum manganese levels and symmetric hyperintensities within the globus pallidus. In this group, 4 patients presented with parkinsonian symptoms, myoclonus, and syndromes with vestibular and vestibular-auditory symptoms. The patients without dialytic treatment presented with neither bilaterally increased T1 MR imaging signal intensity within the globus pallidus nor symptoms of manganism. CONCLUSION: Our preliminary results demonstrated the occurrence of bilateral pallidal hyperintensity on T1-weighted images in all patients undergoing hemodialysis associated with high serum manganese levels, revealing a new association. PMID- 17846195 TI - New morphologic variants of the hand motor cortex as seen with MR imaging in a large study population. AB - BACKGROUND AND PURPOSE: The hand motor cortex (HMC) has been classically described as having an omega or epsilon shape in axial-plane images obtained with CT and MR imaging. The aim of this study was to use MR imaging and Talairach normalization in a large sample population that was homogeneous for age and handedness to evaluate in a sex model a new classification with 5 morphologic variants of the HMC in the axial plane (omega, medially asymmetric epsilon, epsilon, laterally asymmetric epsilon, and null). MATERIALS AND METHODS: Structural brain MR images were obtained from 257 right-handed healthy subjects (143 men and 114 women; mean age, 23.1 +/- 1.1 years) via a Talairach space transformed 3D magnetization-prepared rapid acquisition of gradient echo sequence. The frequencies of the different HMC variants were reported for hemisphere and sex. RESULTS: The new variants of the HMC (medially asymmetric epsilon, laterally asymmetric epsilon, and null) were observed in 2.9%, 7.0%, and 1.8% of the hemispheres, respectively. Statistically significant sex differences were observed: The epsilon variant was twice as frequent in men, and an interhemispheric concordance for morphologic variants was observed only for women. CONCLUSION: The large study population permitted the description of a new morphologic classification that included 3 new variants of the HMC. This new morphologic classification should facilitate the identification of the precentral gyrus in subsequent studies and in everyday practice. PMID- 17846196 TI - Magnetoencephalographic mapping of interictal spike propagation: a technical and clinical report. AB - Distinguishing propagated epileptic activity from primary epileptic foci is of critical importance in presurgical evaluation of patients with medically intractable focal epilepsy. We studied an 11-year-old patient with complex partial epilepsy by using simultaneous magnetoencephalography (MEG) and electroencephalography (EEG). In EEG, bilateral interictal discharges appeared synchronous, whereas MEG source analysis suggested propagation of spikes from the right to the left frontal lobe. PMID- 17846197 TI - The venous distension sign: a diagnostic sign of intracranial hypotension at MR imaging of the brain. AB - BACKGROUND AND PURPOSE: Patients with intracranial hypotension (IH) demonstrate intracranial venous enlargement with a characteristic change in contour of the transverse sinus seen on routine T1-weighted sagittal imaging. In IH, the inferior margin of the midportion of the dominant transverse sinus acquires a distended convex appearance; we have termed this the venous distension sign (VDS). This is distinct from the normal appearance of this segment, which usually has a slightly concave or straight lower margin. This sign is introduced, and its performance as a test for the presence of this disease is evaluated. MATERIALS AND METHODS: The transverse sinuses on T1-weighted sagittal imaging of 15 patients with IH and 15 control patients were independently assessed in a blinded fashion by 3 readers for the presence of a VDS. A present or absent VDS was determined for each patient by each reader, and a consensus result for each patient was determined by unanimity or majority rule. RESULTS: Using the VDS, the readers correctly identified 93% (14 of 15) of the IH patients and similarly 93% (14 of 15) of the control patients. There was a high rate of agreement among the readers for the interpretation of the VDS (multirater kappa = 0.82). The overall sensitivity of the VDS for the diagnosis of intracranial hypotension was 94%. Specificity was also 94%. CONCLUSION: The VDS appears to be an accurate test for the presence or absence of IH and may be helpful in the evaluation of these patients. PMID- 17846198 TI - Proton MR spectroscopy: higher right anterior cingulate N-acetylaspartate/choline ratio in Asperger syndrome compared with healthy controls. AB - BACKGROUND AND PURPOSE: One former study reported higher prefrontal N acetylaspartate (NAA) levels in patients with Asperger syndrome (AS). The objective of the current study was to test the hypothesis that patients with AS would have higher dorsolateral prefrontal and anterior cingulate cortex NAA/creatine (Cr) and that NAA/Cr would be correlated with symptom severity. MATERIALS AND METHODS: NAA/choline (Cho), NAA/Cr, and Cho/Cr values revealed by (1)H-MR spectroscopy in 14 right-handed male patients with AS (6 medicated with risperidone), 17-38 years of age, diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were compared with those of 21 right-handed male controls frequency-matched by age and intelligence quotient scores. RESULTS: Patients with AS had significantly higher anterior cingulate NAA/Cho levels (z = -2.18, P = .028); there was a statistical trend for higher anterior cingulate NAA/Cr (z = -1.81, P = .069) that was significant when only the unmedicated patients with AS were taken into account (z = -1.95, P = .050). There were no significant differences in dorsolateral prefrontal MR spectroscopy values. CONCLUSIONS: Our findings show that individuals with AS had higher NAA/Cho levels in the right anterior cingulate compared with healthy controls and that higher anterior cingulate NAA/Cho levels were correlated with higher Yale Brown Obsessive Compulsive Scale total scores. PMID- 17846199 TI - Decrease in the volume of white matter lesions with improvement of hepatic encephalopathy. AB - MR imaging has found abnormalities compatible with low-grade edema in the brain of patients with cirrhosis that have been related to hepatic encephalopathy. We present 3 patients with hepatic encephalopathy who exhibit supratentorial focal or diffuse white matter lesions compatible with small-vessel brain disease. The volume and number of white matter lesions reduced with the improvement of hepatic encephalopathy, suggesting the participation of the blood-brain barrier in the pathogenesis of brain edema in hepatic encephalopathy. PMID- 17846200 TI - The role of conventional MR imaging sequences in the evaluation of neurocysticercosis: impact on characterization of the scolex and lesion burden. AB - BACKGROUND AND PURPOSE: There are few studies comparing the capacity of lesion detection of conventional MR imaging in neurocysticercosis (NCC). This study was designed to clarify its role in the evaluation of this disease, focusing on the total number of lesions identified and the characterization of the scolex. MATERIALS AND METHODS: MR images from 115 patients were prospectively collected during a 3-year interval, including axial spin-echo (SE) T1-weighted; axial fast SE T2-weighted; axial fluid-attenuated inversion recovery (FLAIR); and gadolinium enhanced axial, coronal, and sagittal SE T1-weighted sequences. They were compared regarding the potential for detection of NCC lesions and specifically of the scolex. RESULTS: Comparing all sequences, we found that FLAIR images were more sensitive to the detection of the scolex (P < .003), whereas the last gadolinium-enhanced T1-weighted series (coronal or sagittal) identified the highest number of lesions (P < .001). CONCLUSION: When dealing with NCC, optimal MR imaging protocols should include FLAIR images to obtain maximal rates of scolex detection. Special attention should be paid to the last gadolinium enhanced sequence, which maximizes the quantification of lesion load. PMID- 17846201 TI - Cerebral cortical and white matter lesions in amyotrophic lateral sclerosis with dementia: correlation with MR and pathologic examinations. AB - BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis with dementia (ALSD) is a progressive neurodegenerative disorder, characterized clinically by motor neuron symptoms and dementia, and pathologically by degeneration of the motor neurons of the brain and spinal cord as well as atrophy of the frontal and/or temporal lobes. So far, there has been no study on the correlation of MR images with histologic findings in ALSD. We studied the correlation of antemortem and postmortem T2-weighted MR images with histologic findings in autopsy-proved cases of ALSD. MATERIALS AND METHODS: Antemortem and postmortem T2-weighted images were compared with histologic findings in 3 autopsy-proved cases of ALSD. RESULTS: Antemortem MR images showed atrophy of the frontal and temporal lobes, which were asymmetric in the medial-ventral part of the temporal lobe. Faint linear T2 hyperintensity was seen in the medial-ventral part of the temporal subcortical white matter in 1 case. Postmortem T2-weighted images showed linear subcortical hyperintensity in the ventral-medial temporal lobe in each case. Histologically, cortical atrophy on MR images showed spongiform change with neuronal loss and gliosis especially in the superficial layers and linear subcortical hyperintensity on T2-weighted images showed degeneration and gliosis in each case. These findings are characteristic histologic changes of ALSD. CONCLUSION: MR imaging of atrophy of the frontal and temporal lobes with linear subcortical hyperintensities in the anteromedial temporal lobe is useful for diagnosis of ALSD. PMID- 17846202 TI - Symmetric temporal abnormalities on MR imaging in amyotrophic lateral sclerosis with dementia. AB - BACKGROUND AND PURPOSE: Our aim was to clarify imaging findings of amyotrophic lateral sclerosis with dementia (ALSD). MATERIALS AND METHODS: T2-weighted MR images (T2WI) of 3 patients with ALSD (2 men, 1 woman; 58-71 years of age) and 21 patients with ALS without dementia (12 men, 9 women; 46-74 years of age) were examined for frontotemporal lobar atrophy and signal-intensity alterations in the white matter of the anterior temporal lobes, corticospinal tracts (CST), and precentral gyri and in precentral cortices. The brain of one of the patients with ALSD was examined at autopsy. RESULTS: All patients with ALSD showed bilateral frontotemporal atrophy mostly with temporal lobe dominance. In the ALSD group, T2WI demonstrated hyperintensity in the subcortical white matter on the medial side of the anterior temporal lobes, whereas in the group without dementia, none showed this imaging finding. MR images demonstrated no abnormal signal-intensity changes in CST in the internal capsule or the brain stem in the ALSD group. In the group without dementia, 6 patients (28.6%) showed this imaging finding. In neuropathologic examinations of the brain of 1 patient with ALSD, myelin-stained sections of the brain demonstrated loss of myelin in the subcortical white matter on the medial side of the anterior temporal white matter. CONCLUSIONS: A symmetric pattern of frontotemporal atrophy and anteromedial subcortical hyperintensities in the temporal lobes on T2WI could be characteristic of ALSD. PMID- 17846203 TI - Axonal damage but no increased glial cell activity in the normal-appearing white matter of patients with clinically isolated syndromes suggestive of multiple sclerosis using high-field magnetic resonance spectroscopy. AB - BACKGROUND AND PURPOSE: Proton MR spectroscopy ((1)H-MR spectroscopy) is a well established method for the in vivo investigation of the normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS). Metabolic changes in NAWM are of special interest in patients with clinically isolated syndromes (CIS) suggestive of MS regarding further prognostic classifications. The purpose of this study was to investigate metabolic alterations in NAWM in patients with CIS with use of high-field (1)H-MR spectroscopy and to compare the results to those in patients with an early course of MS. MATERIALS AND METHODS: With use of a 3T whole-body MR imaging system, single-voxel (1)H-MR spectroscopy (PRESS; TR: 2000 ms; TE: 38 ms and 140 ms) of the parietal NAWM was performed in 20 control subjects, 36 patients with CIS, and 12 patients with MS. Metabolite ratios and concentrations of N-acetylaspartate (tNAA), myo-inositol (mIns), choline, and total creatine (tCr) were determined. RESULTS: Compared with the control group, mean NAWM mIns concentrations were significantly elevated in the MS group (4.56 mmol/L versus 3.75 mmol/L, P = .02) but not in the CIS group (4.04 mmol/L, P = .44). The higher concentration of mIns in the MS group was also reflected in the increased Ins/tCr ratio (P = .02). The mean NAWM tNAA was significantly decreased in both patient groups compared with the control group (CIS, 13.42 mmol/L, P = .02; MS, 12.77 mmol/L versus 14.51 mmol/L, P = .008). CONCLUSIONS: A significant increase of the activity of the glial cells can only be observed in patients with an established diagnosis of MS but not in patients with CIS. Axonal damage occurs already during the first demyelinating episode in patients with CIS as well as in patients with definite MS. PMID- 17846204 TI - Giant cystic widening of Virchow-Robin spaces: an anatomofunctional study. AB - We describe 2 patients with unusual white matter cystic dilations, which could correspond to widening of the perivascular spaces. They underwent morphologic MR imaging with tractography, functional MR imaging (fMRI), and neuropsychological evaluation. fMRI examination showed no functional reorganization of cortical areas. Tractography showed an apparent decrease of white matter tract vectors into the regions of concern. Findings of the neuropsychological examination were normal. It seems that even an extensive cystic dilation of white matter does not deteriorate brain function. PMID- 17846205 TI - Human subinsular asymmetry studied by diffusion tensor imaging and fiber tracking. AB - BACKGROUND AND PURPOSE: Our aim was to improve our understanding of the subinsular white matter microstructural asymmetries in healthy right-handed subjects. Structural brain asymmetries could be related to functional asymmetries such as hemisphere language dominance or handedness. Besides the known gray matter asymmetries, white matter asymmetries could also play a key role in the understanding of hemispheric specialization, notably that of language. MATERIALS AND METHODS: White matter asymmetries were studied by diffusion tensor imaging at 1.5T (41 diffusion-gradient directions; b-value set to 700 s/mm(2); matrix, 128(2); in-plane resolution, 1.875 x 1.875 mm; section thickness, 2.0 mm) and fiber tracking (BrainVISA software). The main white matter bundles passing through the subinsular area were segmented, and fractional anisotropy (FA) was measured along each of the segmented bundles. RESULTS: In line with published results, we found an asymmetry of the arcuate fasciculus and the subinsular white matter, namely left-greater-than-right FA in right-handed controls. Furthermore, by segmenting major tracts coursing through this region, we showed that the subinsular portions of the uncinate fasciculus (UF) and the inferior occipitofrontal fasciculus (IOF) contribute to this FA asymmetry. Those tracts have been reported to be likely implicated in the language network. CONCLUSION: Because the left hemisphere hosts language functions in most right-handers, the significant leftward asymmetry observed within the arcuate fasciculus, the subinsular part of the UF and IOF may be related to the hemispheric specialization for language. PMID- 17846206 TI - Imaging characteristics of recurrent pleomorphic adenoma of the parotid gland. AB - BACKGROUND AND PURPOSE: Pleomorphic adenoma is the most common parotid neoplasm. It has a relatively high rate of recurrence after surgery. Imaging features of recurrent parotid pleomorphic adenoma have been infrequently reported in the radiology literature. In the present study, we reviewed our institutional experience with imaging of recurrent parotid pleomorphic adenomas. MATERIALS AND METHODS: Retrospective imaging and chart review of 24 patients (9 men, 15 women; age, 29-63 years) with recurrent pleomorphic adenoma of the parotid were performed. Images were reviewed as to the margins, site, multiplicity, signal intensity, and enhancement pattern of the recurrent lesions by 2 neuroradiologists. RESULTS: We found a high incidence of multiple lesions in the operative bed, most of which were extremely bright on T2-weighted images; some of the lesions demonstrated a cystic appearance with peripheral enhancement. We also noted tiny lesions in the subcutaneous fat and in regions distant from the immediate operative bed. CONCLUSION: Although recurrent disease is usually clinically apparent, sometimes prior surgical history is lacking or recurrence may be detected on routine surveillance imaging after initial surgery. The presence of solitary or multiple subcutaneous T2 hyperintense lesions in the operative bed, subcutaneous fat, and/or spaces adjacent to the parotid in patients with prior parotidectomy for pleomorphic adenoma is consistent with the diagnosis of neoplastic recurrence. The radiologist should maintain a high index of suspicion for recurrent pleomorphic adenoma with this characteristic imaging appearance. PMID- 17846207 TI - Pathologic changes of the lateral pterygoid muscle in patients with derangement of the temporomandibular joint disk: objective measures at MR imaging. AB - BACKGROUND AND PURPOSE: The superior head of the lateral pterygoid muscle (SHLP), which inserts on the anterior disk of the temporomandibular joint (TMJ), can spasm, contracting and exerting forward traction on the disk. This mechanism can lead to anterior displacement. In TMJ dysfunction, it is hypothesized that the SHLP will demonstrate morphologic changes with measurable changes in signal intensity related to atrophy or muscular edema, or both. The goal of this study was to evaluate the lateral pterygoid muscle (LPM) in patients with TMJ dysfunction. MATERIALS AND METHODS: Patients with displacement of the TMJ disk with and without reduction were identified through a review of radiology reports. Absolute measurements of thickness as well as region-of-interest measurements were placed over the 2 heads of the LPM bilaterally on sagittal T1- and T2 weighted images. Statistically significant differences between the superior and inferior heads of the LPM were calculated with use of a 1-tailed Student t test and were correlated with the degree of disk derangement. RESULTS: In patients with disk derangement, significantly increased region-of-interest values on T2- and T1-weighted images were demonstrated within the SHLP. No patients with anatomically normal disks demonstrated a statistically significant difference in region-of-interest values between the superior and inferior heads of the LPMs. CONCLUSION: Correlation between increased region-of-interest values and pathologic alteration of the relationship between the condylar head and disk was identified. In patients with displacement of the anterior disk with and without reduction, region-of-interest values were significantly increased, which indicates abnormal signal intensity involving the superior head of the LPM. PMID- 17846208 TI - Has the degree of contrast enhancement with MR imaging in laryngeal carcinoma added value to anatomic parameters regarding prediction of response to radiation therapy? AB - BACKGROUND AND PURPOSE: Our aim was to retrospectively investigate the prognostic significance of the degree of contrast enhancement in tumors and its additional value in previously considered MR imaging parameters with regard to local control of laryngeal cancer treated with radiation therapy (RT) alone. MATERIALS AND METHODS: Pretreatment MR images of 64 consecutive patients (54 men and 10 women, 43-80 years of age) with supraglottic and glottic cancer were retrospectively reviewed on clinical and previously considered MR imaging parameters such as tumor involvement of specific laryngeal anatomic subsites, including laryngeal cartilages, tumor volume, extralaryngeal tumor spread, and, in addition, the degree of contrast enhancement. Clinical and MR imaging parameters were associated with regard to local control at 2 years by using the Cox regression model. "Local control" was defined as absence of primary tumor recurrence. RESULTS: When using a threshold of the mean average contrast enhancement of 77%, the 2-year local control rate in the groups of patients with a degree of enhancement below and above this threshold was 57% and 70%, respectively (P=.3). Enhancement of tumor tissue in pre-epiglottic space (PES) was low, most probably due to its adipose tissue and poor vascular content, whereas tumor tissue involving paraglottic space (PGS) did enhance. Results of multivariate analysis indicated that the degree of contrast enhancement yielded the prognostic information (P=.07) with 2 independent prognostic factors: primary tumor volume (P=.007) and subglottic extension (P=.002) with regard to local control. Using these previously mentioned 3 MR imaging parameters as potential risk factors, we defined 4 categories, resulting in the following local control rates respectively: 90% for the group without risk factors, 73% for the group with 1, 60% for the group with 2, and finally 0% for the group with 3 risk factors, which was significantly lower than the rates in previous risk groups (P < .001). CONCLUSION: PES has a lower degree of contrast enhancement than the PGS and may correlate with the worse outcome. Including a low degree of contrast enhancement as a parameter to primary tumor volume and subglottic extension may increase the predictive value of MR imaging for local outcome and may be helpful to identify a subset of patients whose tumors all recurred locally within 2 years after primary RT. PMID- 17846209 TI - Monitoring of gustatory stimulation of salivary glands by diffusion-weighted MR imaging: comparison of 1.5T and 3T. AB - BACKGROUND AND PURPOSE: Our aim was to compare different field strengths monitoring physiologic changes due to oral stimulation of parotid glands by using diffusion-weighted (DW) echo-planar imaging (EPI). MATERIALS AND METHODS: Twenty seven healthy volunteers were examined with a DW-EPI sequence at 1.5T and 3T before and after oral stimulation with commercially available lemon juice. The b factors used were 0, 500, and 1000 s/mm(2). Apparent diffusion coefficient (ADC) maps were evaluated with a manually placed region of interest including the entire parotid gland. For comparison of results, a Student t test was used on the basis of the mean of the volunteer median values. To compare both field strengths, we calculated the Pearson correlation coefficient (r). RESULTS: DW-EPI MR imaging visualized the parotid glands of all volunteers. With 1.5T, the mean ADC before stimulation was 1.12 x 10(-3) mm(2)/s +/- 0.08 x 10(-3) mm(2)/s. After stimulation with lemon juice, the ADC increased to 1.18 x 10(-3) mm(2)/s +/- 0.09 x 10(-3) mm(2)/s. For 3T, the ADC before stimulation was 1.14 x 10(-3) mm(2)/s +/ 0.04 x 10(-3) mm(2)/s, with an increase to 1.17 x 10(-3) mm(2)/s +/- 0.05 x 10( 3) mm(2)/s after stimulation. For both field strengths, the increase in ADC after stimulation was significant (P < .001). High correlations between both field strengths were found pre- and poststimulation (r = 0.955, and 0.936, respectively). CONCLUSION: DW-EPI MR imaging allows monitoring of physiologic changes due to oral stimulation of parotid glands by using DW imaging with high correlation between 1.5T and 3T. PMID- 17846210 TI - MR imaging of labial glands. AB - BACKGROUND AND PURPOSE: The labial salivary gland is a site of occurrence of tumors and cysts, and it serves as the biopsy site for the diagnosis of Sjogren syndrome. However, its imaging features have not been well understood. Here we attempted to depict the labial gland by high-resolution MR imaging. MATERIALS AND METHODS: The labial glands from 89 patients without Sjogren syndrome, 14 patients with Sjogren syndrome, and 3 patients with tumor or cyst of the lips were imaged by using a 1.5T MR imager with a 47- or 110-mm surface coil. RESULTS: The upper and lower labial glands consisted of 1-3 layers of gland clusters, each of which had high signal intensity on T1-weighted and fat-suppressed T2-weighted images and was readily enhanced after gadolinium injection. The posterior parts of the glands were thicker than the anterior parts. The gland areas in the lower lips (186 +/- 64 mm(2) in women and 192 +/- 68 mm(2) in men) were greater than those in the upper lips (140 +/- 46 mm(2) in women and 162 +/- 66 mm(2) in men). We did not find any significant age-related changes or sex differences in the gland area. The labial gland areas were smaller in the patients with Sjogren syndrome than in patients without Sjogren syndrome, though the difference was significant only in the upper lips (104 +/- 53 mm(2)). CONCLUSION: This is the first report describing imaging features of the labial salivary glands. High-resolution MR imaging can readily delineate the labial glands. PMID- 17846211 TI - Severe diffuse systemic amyloidosis with involvement of the pharynx, larynx, and trachea: CT and MR findings. AB - Amyloidosis is a term applied to a diverse group of disorders that share the deposition of amyloid protein in various extracellular tissues. Systemic amyloidosis may involve almost any organ system in the body including regions in the head and neck; however, pharyngeal involvement is rare, with only 12 cases having been previously reported. Ten of these cases were localized disease, and only 2 cases were systemic amyloidosis. We present the case of a patient with severe diffuse systemic amyloidosis with extensive involvement of the pharynx, larynx, trachea, lungs, eyelids, and breasts. We also review the imaging characteristics and pertinent literature. PMID- 17846212 TI - Radiation dose of the lens in trans-sphenoidal pituitary surgery: pros and cons of a conventional setup using fluoroscopic guidance and CT-based neuronavigation. AB - BACKGROUND AND PURPOSE: We determined the radiation dose in patients' lenses during pituitary surgery with either conventional fluoroscopy or CT-guided neuronavigation. MATERIALS AND METHODS: Thermoluminescent dosimeters (TLD-100H) were attached to the lenses of an anthropomorphic Alderson-Rando head phantom. Simulation of the conventional setup of continuous fluoroscopy (61 kV peak, 2.01 mAs) with collimation and automatic exposure control was used with 1 TLD being removed every 5 seconds, followed by another experiment with 1 being removed every 30 seconds. For CT-guided neuronavigation, a spiral of 3-mm-thick sections without gap was performed (140 kV, 220 mA). Patients' charts (n = 87) were reviewed in terms of radiation exposure and perioperative complications. RESULTS: Radiation dose is distance-dependent (P < .002), with an exposure-time-dependent linear increase (R(2) = 99.27, P < .0001) close to the primary beam only. The radiation dose of the CT (mean, 39.39 mGy) was fivefold higher compared with the maximal time of 3 minutes (8 mGy) reached in our patients by using the conventional setup. CT offers more detailed 3D anatomy available at any time intraoperatively. Tolerance doses needed to develop cataracts were not reached, and perioperative complications occurred without significant differences (Mann Whitney U test, P = .39) using either method. Continuous use of fluoroscopy reached the mean value of CT after 14.33 minutes. CONCLUSION: Neuronavigation provides better anatomic information and avoids repetitive exposure and accumulation to the staff, with the disadvantage of an increased radiation exposure to the patient causing at least no acute harm. Long-term effects are hard to prove but cannot be neglected either. PMID- 17846213 TI - MR imaging features of giant reservoir formation in the orbit: an unusual complication of Ahmed glaucoma valve implantation. AB - We report the MR imaging findings of an unusually large fluid collection, so called giant reservoir, around an Ahmed glaucoma valve implant that caused progressive proptosis in a patient with posttraumatic glaucoma. Although other cystic lesions of the juxtalacrimal area of the orbit, such as dermoid cyst, can present similar imaging findings, the characteristic morphology and location should lead the radiologist to the correct nature of this cystic lesion. PMID- 17846214 TI - Endovascular treatment of middle cerebral artery aneurysms as first option: a single center experience of 92 aneurysms. AB - BACKGROUND AND PURPOSE: We conducted a retrospective evaluation of the results of endovascular treatment (EVT) of middle cerebral artery aneurysms (MCAAs) in a center where embolization is the first treatment option considered. MATERIALS AND METHODS: Ninety-two MCAAs were diagnosed in 87 patients between September 2001 and January 2006. The strategy of treatment (endovascular versus surgical), the clinical and angiographic results of embolization, and the ensuing complications are described. RESULTS: Initially, 59 aneurysms (64.1%) in 55 patients were embolized, 18 (19.6%) were clipped, and 15 (16.3%) were not treated. Four endovascular procedures failed (7.3%), and 55 aneurysms in 51 patients were finally treated by embolization. During the procedure, complications occurred in 13 patients (25.5%) comprising 3 ruptures and 10 thromboembolisms. In the follow up, 4 patients having a preoperative complication had a modified Rankin scale more than 2 (3 patients [5.9%]) or died (1 patient [2.0%]). Of the 55 embolized aneurysms, according to the Raymond scale, 23 (41.8%) were completely occluded, 24 (43.6%) retained a residual neck, and 8 (14.6%) were residual at the end of the first procedure. No bleeding was detected during the follow-up period in the embolized patients. CONCLUSION: EVT of MCAA is effective for preventing rebleeding episodes within the first year of treatment judging by historical controls. The real question is whether clipping or coiling of MCAAs is better in terms of reducing rebleeding rates and complications rates in the long term, and such a determination would require a far larger number of patients over a much longer observation period. PMID- 17846215 TI - Distal aneurysms of cerebellar arteries: incidence, clinical presentation, and outcome of endovascular parent vessel occlusion. AB - BACKGROUND AND PURPOSE: The aim of this retrospective study was to report the incidence, clinical presentation, and midterm clinical and imaging results of endovascular parent vessel occlusion of 11 patients with 13 distal cerebellar artery aneurysms. MATERIALS AND METHODS: Between January 1995 and December 2006, 2201 aneurysms were treated in our institution. Thirteen aneurysms in 11 patients were located on distal cerebellar arteries (incidence, 0.6%), 8 of them arising from vessels feeding small arteriovenous malformations. There were 6 men and 5 women, ranging from 44 to 70 years of age. One patient with a superior cerebellar artery aneurysm presented with isolated trochlear nerve palsy. Ten patients presented with subarachnoid and intraventricular hemorrhage, and most patients were in poor clinical condition on admission. Aneurysm location was the superior cerebellar artery in 3, the anterior inferior cerebellar artery in 5, and the posterior inferior cerebellar artery in 5. Two patients had 2 aneurysms each. RESULTS: Eleven aneurysms were treated by simultaneous coil occlusion of the aneurysm and parent artery or occlusion of the parent artery just proximal to the aneurysm. Clinical follow-up was at a mean of 16.5 months (range, 2-40 months). Infarction in the territory of the occluded vessel was apparent on follow-up imaging in 5 of 11 patients, all without functional impairment. CONCLUSION: Distal cerebellar artery aneurysms are rare. Most patients present with poor grade hemorrhage. Endovascular parent vessel occlusion is effective in excluding the aneurysm from the circulation. In most patients, adequate collateral circulation prevents infarction in the territory of the occluded vessel. In this series, when infarction did occur, the clinical consequences were limited. PMID- 17846216 TI - A new covered stent designed for intracranial vasculature: application in the management of pseudoaneurysms of the cranial internal carotid artery. AB - BACKGROUND AND PURPOSE: The management of intracranial pseudoaneurysms is controversial. The purpose of this study was to provide a preliminary evaluation of the clinical efficacy of a Willis covered stent specially designed for the intracranial vasculature in the management of a pseudoaneurysm of the cranial internal carotid artery (CICA). MATERIALS AND METHODS: Eight patients with pseudoaneurysms of the CICA were treated with use of the Willis covered stent. The flexibility of the entire stent system was gauged from the resistance met when reaching the target lesion and was categorized as no resistance, no apparent resistance, or resistance that could be overcome. The apposition of the Willis stent after deployment was scored as excellent with no endoleak, good with a small endoleak, or bad with an apparent endoleak. Follow-up angiography was performed 3 to 12 months after placement of the stent, and angiographic assessments were categorized as endoleak, stenosis of the covered segment of vessel, or occlusion of parent arteries. Follow-up clinical evaluations were also performed, and outcomes were graded as full recovery, improvement, unchanged, and aggravation. RESULTS: Endovascular treatment was technically successful in all aneurysms without procedural-related complications, and all of the stents were easily navigated to the targeted lesions in the CICA. Complete resolution of the pseudoaneurysm was observed in 6 patients immediately after the procedure, and a minimal endoleak into the aneurysm persisted in 2 patients. No morbidity or mortality and no technical adverse event occurred. A follow-up angiogram confirmed complete reconstruction of the internal carotid artery, with no recurrent aneurysmal filling and no occurrence of stenosis in the area of the stent. By the final follow-up visit, 4 patients had fully recovered, 3 had improved, and 1 patient's condition was unchanged. CONCLUSION: On the basis of our preliminary experience, the Willis covered stent specially designed for the intracranial vasculature can manage a CICA pseudoaneurysm safely and effectively, but longer follow-up and expanded clinical trials are needed. PMID- 17846217 TI - Efficient transmicrocatheter delivery of functional fibroblasts with a bioengineered collagen gel-platinum microcoil complex: toward the development of endovascular cell therapy for cerebral aneurysms. AB - BACKGROUND AND PURPOSE: Endoaneurysmal implantation of fibroblasts may promote healing of aneurysms and reduce recanalization after therapeutic embolization. The purpose of our study was to develop a device for delivery of fibroblasts with use of current microcoil technology. MATERIALS AND METHODS: Cell carrier devices and cell-free devices were fabricated by associating collagen gels (with or without fibroblasts) with platinum microcoils. During the propagation of control cell carrier devices for 1 week in culture, cell-mediated gel contraction (CMGC) occurred. Modified cell carrier devices created by glutaraldehyde cross-linking, ascorbate coculture, or extended CMGC were also characterized in vitro. Devices were deployed through microcatheters (533 microm lumen, 160 cm length). Gel retention, cell retention, cell death, and the ability to support local cell migration were analyzed in vitro. RESULTS: Cell viability was reduced by glutaraldehyde cross-linking but not by microcatheter transit. During microcatheter transit, cell carrier devices liberated minimal particulate matter and cellular DNA. Liberated particulate matter was reduced by glutaraldehyde cross-linking (P < .05) and extended CMGC (P < .04). Only cell carrier devices treated with glutaraldehyde cross-linking did not exhibit cell migration after microcatheter transit. Passage of cell-free devices through microcatheters sheared off most of their collagen gel. CONCLUSION: Collagen gel-platinum microcoil complexes can mediate efficient transmicrocatheter delivery of viable, migration-capable fibroblasts. CMGC is a necessary component of the process of gel stabilization that enables successful microcatheter transit. Although extended CMGC and glutaraldehyde cross-linking enhance gel stabilization, glutaraldehyde cross-linking decreases cell viability and migratory potential. PMID- 17846218 TI - Placement of covered stents for carotid blowout in patients with head and neck cancer: follow-up results after rescue treatments. AB - BACKGROUND AND PURPOSE: Placement of a covered stent to control carotid blowout (CB) in malignant tumors of the head and neck has been reported to be an effective treatment. However, it is not uncommon to encounter recurrent hemorrhage. The purpose of this study was to evaluate the follow-up results of patients treated with covered stents. MATERIALS AND METHODS: We retrospectively reviewed the results of 7 consecutive patients who underwent placement of a covered stent to control CB. Most of them had poor wound healing because of previous irradiation, surgery, or both. The initial procedures were successful in all patients. Their clinical course was reviewed for rebleeding, additional endovascular treatments in recurrent cases, and outcomes. RESULTS: Recurrence developed in 6 of 7 patients. The interval between the first procedure and the hemorrhagic event was from 3 to 44 days. In 6 patients who had a recurrent CB, 4 had rebleeding from the previous site of the stent, whereas 2 other patients experienced recurrent bleeding in a different area from the site of the stent. Additional endovascular treatments were carried out in all affected patients by another insertion of a covered stent (n = 3), coil embolization (n = 2), or insertion of a covered stent followed by permanent arterial occlusion (n = 1). CONCLUSION: Placement of a covered stent in patients with head and neck cancer who sustain CB showed frequent rebleeding despite favorable initial rescue results. Recurrent CB at the previous stent site developed frequently in patients with uncontrolled wound infection. Concomitant or short-interval arterial trapping should be considered selectively in those conditions. PMID- 17846219 TI - Dural arteriovenous fistula involving the posterior condylar canal. AB - Although dural arteriovenous fistulas (DAVFs) occur in any structure that is covered by the dura mater, DAVFs at the posterior condylar canal have not been reported. We present a DAVF that involves the posterior condylar canal and drains into the posterior condylar vein and the occipital sinus, which was treated by selective transvenous embolization. Knowledge of venous anatomy of the craniocervical junction and careful assessment of the location of the arteriovenous fistula can contribute to successful treatment. PMID- 17846220 TI - Myelination as assessed by conventional MR imaging is normal in young children with idiopathic developmental delay. AB - BACKGROUND AND PURPOSE: A common isolated reported finding in brain imaging studies on developmentally delayed children is delayed myelination. We hypothesized that brain MR imaging scans of these children would show delayed subcortical myelination of white matter with specific involvement of the subcortical U-fibers as these represent terminal zones of myelination and are the last areas to myelinate. MATERIALS AND METHODS: A total of 93 children (31 controls, 62 with idiopathic developmental delay [IDD]) aged 17 to 46 months were identified on the basis of having brain MR imaging for evaluation of IDD (cases) or for another condition (controls). Children with diseases that primarily affect white matter or overt intracranial lesions or malformations were excluded. IDD was defined as psychomotor retardation without a clear cause on the basis of history, physical, genetic, metabolic, and neuroimaging examinations. Developmental quotients (DQs) were calculated for all children with IDD on the basis of clinical history, examination, and psychometric testing. Three board certified pediatric neuroradiologists examined axial T2-weighted brain images and used a published scoring system to rate the extent of myelination in the frontal, temporal, parietal, and peritrigonal brain regions. In addition, subcortical U fibers in the frontal, temporal, and parietal lobes were scored separately. Data were analyzed at both the intraobserver and interobserver levels, and scores were compared between groups and tested for interactions with age and DQ. RESULTS: There were no differences in the timing or extent of myelination in the control and IDD groups at any age in any brain region. In the IDD group, there was no relationship between myelination scores and DQ or developmental domain. CONCLUSIONS: Our findings did not support the hypothesis that there is a correlation between IDD and the maturity of myelination, including the terminal zones, as seen on conventional brain MR imaging. Neuroimaging evaluation of maturity of subcortical myelination is not a marker of IDD in young children, and the isolated "finding" of delayed myelination should be interpreted with caution. PMID- 17846221 TI - Autosomal recessive spastic ataxia of Charlevoix-Saguenay: a report of MR imaging in 5 patients. AB - We present findings on MR imaging in 5 patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). In the literature, early atrophy of the superior vermis as well as progressive atrophy of the cerebellar hemispheres and cervical cord was described. We found linear hypointensity on T2 and T2 fluid attenuated inversion recovery-weighted images in the pons in all of our 5 patients. PMID- 17846222 TI - Facial hemangioma and hemispheric migration disorder: presentation of 5 patients. AB - BACKGROUND AND PURPOSE: The association of cortical organization disorders with facial hemangiomas or vascular malformations has been described in only a few reports. The purpose of this study was to show the close association of these cutaneous anomalies with cortical dysplasias and intracranial vascular abnormalities. MATERIALS AND METHODS: Five patients, all women, with cutaneous vascular abnormalities, 4 with hemangioma and 1 with vascular malformation, were studied with MR and MR angiography. RESULTS: All 5 of the patients showed cortical dysplasia. The cutaneous lesions involved the left frontal region, ipsilateral to the cerebral hemisphere with cortical dysplasia, in all of the patients. Four patients had seizures that responded well to antiepileptic drugs. Hemispheric hypoplasia was associated with the cortical dysplasia in all 5 of the patients. Arterial abnormalities were found in all of the patients, consisting of aplasia of the ipsilateral internal carotid artery in 2, persistence of the trigeminal artery in 2, persistence of both proatlantal arteries and double kinking in the internal carotid artery in 1, and origin of both anterior cerebral arteries from the same internal carotid in all 5 of the patients, 1 of whom also showed an intracavernous anterior cerebral artery origin of the same side of the hemispheric hypoplasia and polymicrogyria. Seizures and mild psychomotor delay could be caused by the cortical dysplasia and the hemispheric hypoplasia. CONCLUSIONS: The presence of many congenital vascular abnormalities in this series suggests that facial hemangioma and vascular malformations may be in close relationship with cortical and vascular abnormalities. The reason that the vascular and cortical abnormalities occurred in the left side in all 5 of the patients and the mechanism underlying the association of both malformations are unclear. A genetic origin is suggested. PMID- 17846223 TI - Angle-corrected imaging transcranial doppler sonography versus imaging and nonimaging transcranial doppler sonography in children with sickle cell disease. AB - BACKGROUND AND PURPOSE: Nonimaging transcranial Doppler sonography (TCD) and imaging TCD (TCDI) are used for determination of the risk of stroke in children with sickle cell disease (SCD). The purpose was to compare angle-corrected, uncorrected TCDI, and TCD blood flow velocities in children with SCD. MATERIALS AND METHODS: A total of 37 children (mean age, 7.8 +/- 3.0 years) without intracranial arterial narrowing determined with MR angiography, were studied with use of TCD and TCDI at the same session. Depth of insonation and TCDI mean velocities with and without correction for the angle of insonation in the terminal internal carotid artery (ICA) and middle (MCA), anterior (ACA), and posterior (PCA) cerebral arteries were compared with TCD velocities with use of a paired t test. RESULTS: Two arteries were not found on TCDI compared with 15 not found on TCD. Average angle of insonation in the MCA, ACA, ICA, and PCA was 31 degrees , 44 degrees , 25 degrees , and 29 degrees , respectively. TCDI and TCD mean depth of insonation for all arteries did not differ significantly; however, individual differences varied substantially. TCDI velocities were significantly lower than TCD velocities, respectively, for the right and left sides (mean +/- SD): MCA, 106 +/- 22 cm/s and 111 +/- 33 cm/s versus 130 +/- 19 cm/s and 134 +/- 26 cm/s; ICA, 90 +/- 14 cm/s and 98 +/- 27 cm/s versus 117 +/- 18 cm/s and 119 +/ 23 cm/s; ACA, 74 +/- 24 cm/s and 88 +/- 25 cm/s versus 105 +/- 23 cm/s and 105 +/- 31 cm/s; and PCA, 84 +/- 27 cm/s and 82 +/- 21 cm/s versus 95 +/- 23 cm/s and 94 +/- 20 cm/s. TCD and angle-corrected TCDI velocities were not statistically different except for higher angle-corrected TCDI values in the left ACA and right PCA. CONCLUSION: TCD velocities are significantly higher than TCDI velocities but are not different from the angle-corrected TCDI velocities. TCDI identifies the major intracranial arteries more effectively than TCD. PMID- 17846224 TI - Head trauma. PMID- 17846225 TI - Retraction. Dynamic upper airway soft-tissue and caliber changes in healthy subjects and snoring patients. PMID- 17846227 TI - CD74 induces TAp63 expression leading to B-cell survival. AB - Most mature follicular B cells circulate within the periphery in a quiescent state, without actively contributing to an acute immune response. Lasting B-cell persistence in the periphery is dependent on survival signals that are transduced by cell surface receptors. We recently demonstrated that cell surface CD74 controls mature B-cell survival. Stimulation of cell surface CD74 leads to NF kappaB activation, which enables entry of the stimulated B cells into the S phase, induction of DNA synthesis, and cell division, and augments the expression of survival genes. In the present study, we investigated CD74 target genes to determine the identities of the molecules whose expression is modulated by CD74, thereby regulating B-cell survival. We report that CD74 activates the p65 member of the NF-kappaB family, which in turn up-regulates the expression of p53-related TAp63 proteins. TAp63 then binds and transactivates the Bcl-2gene and induces the production of Bcl-2 protein, thereby providing the cells with increased survival capacity. Thus, the CD74/NF-kappaB/TAp63 axis defines a novel antiapoptotic pathway in mature B cells, resulting in the shaping of both the B-cell repertoire and the immune response. PMID- 17846228 TI - The TCL1 oncoprotein inhibits activation-induced cell death by impairing PKCtheta and ERK pathways. AB - The TCL1/MTCP1 oncogenes were identified on the basis of their involvement in T cell prolymphocytic leukemia (T-PLL). TCL1 and MTCP1 proteins directly interact with AKT and modulate the AKT signal-transduction pathway, but the relevance of this mechanism in leukemogenesis remains unclear. We investigate the biologic functions of TCL1 in the T-cell lineage using various cell lines, and primary malignant and normal lymphocytes. In the Jurkat cell line, expression of TCL1 had no effect in unstimulated cells, whereas it abrogated activation-induced cell death (AICD). These cellular effects were concomitant with a major inhibition by TCL1 of PKCtheta and ERK pathways. Secondly, the TCL1-driven T-cell leukemia cell line SUP-T11 was shown to have impaired PKCtheta and ERK phosphorylation upon stimulation, which were restored by TCL1 inhibition using RNA interference. Finally, defects in these pathways were also observed in primary malignant (T PLL) and transduced normal T lymphocytes expressing TCL1. Altogether, our data demonstrated that TCL1 inhibits AICD in T cells by blocking PKCtheta and ERK activation, upon cellular activation. PMID- 17846226 TI - Phase 2 study of pegylated liposomal doxorubicin in combination with interleukin 12 for AIDS-related Kaposi sarcoma. AB - Thirty-six patients with AIDS-associated Kaposi sarcoma (KS) requiring chemotherapy were treated for six 3-week cycles of pegylated liposomal doxorubicin (20 mg/m(2)) plus interleukin-12 (IL-12; 300 ng/kg subcutaneously twice weekly), followed by 500 ng/kg subcutaneous IL-12 twice weekly for up to 3 years. All received highly active antiretroviral therapy (HAART). Twenty-two had poor-prognosis KS (T(1)S(1)). Thirty patients had a major response, including 9 with complete response, yielding an 83.3% major response rate (95% confidence interval: 67.2%-93.6%). Median time to first response was 2 cycles. Median progression was not reached at median potential follow-up of 46.9 months. Of 27 patients with residual disease when starting maintenance IL-12, 15 had a new major response compared with this new baseline. The regimen was overall well tolerated; principal toxicities were neutropenia, anemia, transaminitis, and neuropsychiatric toxicity. Patients had increases in serum IL-12, interferon gamma, and inducible protein-10 (IP-10), and these remained increased at weeks 18 and 34. The regimen of IL-12 plus liposomal doxorubicin yielded rapid tumor responses and a high response rate in patients with AIDS-KS receiving HAART, and responses were sustained on IL-12 maintenance therapy. A randomized trial of IL 12 in this setting may be warranted. This study is registered at (http://www.clinicaltrials.gov) as no. NCT00020449. PMID- 17846229 TI - Pathology of mucopolysaccharidosis IIIA in Huntaway dogs. AB - Dogs with mucopolysaccharidosis (MPS) IIIA were bred within an experimental colony. As part of characterizing them as a model for testing therapeutic strategies for the analogous disease of children, a pathologic study was undertaken. By histology, there were variably stained storage cytosomes within neurons, including many that stained for gangliosides. On ultrastructure examination, these cytosomes contained either moderately dense granular material, tentatively interpreted as precipitated glycosaminoglycan; a variety of multilaminar bodies, interpreted as being associated with secondary accumulation of gangliosides; or a mixture of both types. In the liver, storage vesicles also contained excess glycogen as a secondary storage product. In various tissues, there were large foamy macrophages. In the brain, many of these were in juxtaposition with neurons, and, on ultrastructure examination, they contained storage cytosomes similar to those in neurons. However, the neuron in association with such a macrophage frequently showed little such material. PMID- 17846230 TI - Cutaneous neoplasms in pet rabbits: a retrospective study. AB - Over a 16-year period, 190 tumors and tumorlike lesions from 179 pet rabbits were submitted for histopathologic examination. A total of 23 different tumor types and 1 tumorlike lesion were diagnosed. The most common diagnoses were trichoblastoma, collagenous hamartoma, and Shope fibroma. Viral-induced tumors were Shope fibroma (19) and Shope papilloma (2). Common nonviral epithelial tumors included trichoblastoma (59), squamous cell carcinoma (5), squamous papilloma (4), trichoepithelioma (3), and apocrine carcinoma (3). Common mesenchymal tumors were lipoma (10), liposarcoma (3), myxosarcoma (9), malignant peripheral nerve sheath tumor (8), fibrosarcoma (7), and leiomyosarcoma (4). Malignant melanoma was diagnosed in 8 rabbits. Collagenous hamartomas were diagnosed in 26 rabbits. Mesenchymal proliferations occurred significantly more often in male rabbits than in females. Collagenous hamartomas and myxosarcomas occurred exclusively in male animals, and 3 rabbits had multiple collagenous hamartomas. Immunohistochemistry was applied in cases in which a definite diagnosis could not be reached on hematoxylin and eosin slides. Follow-up information was received in 19 cases. Carcinomas recurred (2 of 3) or metastasized (1 of 3), whereas sarcomas frequently recurred (7 of 12). One malignant melanoma (1 of 3) and one poorly differentiated round cell neoplasm recurred (1 of 1). This is the first comprehensive retrospective analysis on skin neoplasia in pet rabbits. PMID- 17846231 TI - Myocarditis associated with foot-and-mouth disease virus type O in lambs. AB - The present study describes the pathogenetic mechanisms of myocarditis in 9 lambs that died in a foot-and-mouth disease outbreak in Samsun, Turkey. In all the heart samples tested, ELISA and sequencing for phylogenetic analyses showed that the virus, namely O/TUR/Samsun/05, was associated with the PanAsia pandemic strain of foot-and-mouth disease virus (FMDV) type O. The lambs had myocardial lesions but no typical vesicular lesions. In situ reverse transcription showed that many cardiomyocytes and some interstitial cells were positive for FMDV type O. Inflammatory infiltration, hyaline degeneration, and necrosis of sheets of myocytes were observed. The cellular infiltrates were mononuclear cells, including many lymphocytes, macrophages, a few plasma cells, and neutrophils. Major histocompatibility complex Class II+ dendritic and mononuclear cells, gammadelta T cells, CD172A+ and CD14+ macrophages and monocytes, and IgM+ B cells were detected mainly in the infected hearts. Inducible nitric oxide synthetase (iNOS) was seen mostly in areas of inflammation infiltrated by large numbers of cells. Of the 2 alpha-subunits of integrin known to be used as receptors by FMDV in epithelial tissues, CD49e (integrin alpha5) was detected in the membranes of cardiac myocytes with intercalated discs, but CD51 (integrin alphaV) was not detected in cardiac myocytes from infected or normal lambs. Interstitial and inflammatory cells were positive for both integrin subunits. The terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL)-positive signal was detected in the nuclei of both cardiac myocytes and interstitial cells from infected lambs. These findings suggest that the iNOS expressed by inflammatory cells in lesions may have a deleterious effect on cardiac myocytes in these lesions. PMID- 17846232 TI - Cellular characterization of multidrug resistance P-glycoprotein, alpha fetoprotein, and neovascular endothelium-associated antigens in canine hepatocellular carcinoma and cirrhotic liver. AB - P-glycoprotein (P-gp), which is encoded by the multidrug resistance gene (MDR-1); alpha fetoprotein (AFP); and vascular endothelium-associated antigens are well known markers for human and canine hepatic diseases. We obtained liver tissues from 5 dogs with hepatocellular carcinoma (HCC) and 12 dogs with cirrhosis, and we performed histopathologic and immunohistochemical evaluations using anti-P-gp, anti-AFP, anti-CD31, and anti-CD34 antibodies. P-gp was expressed at higher levels in HCC than in cirrhotic livers ( P < .01), and was most commonly localized in biliary canaliculi and small ductuli. AFP was localized mainly in the cytoplasm in HCC ( P < .01) and in a few cases of cirrhosis. In both HCC and cirrhosis, the AFP-positive cells were morphologically similar to normal hepatocytes and showed an even cytoplasmic distribution of AFP. The endothelial markers CD31 and CD34 were used to investigate vascular distribution. CD31 was expressed strongly in the portal area and parenchyma in HCC, but it was rarely observed in the parenchyma in cirrhosis. CD34 expression could not be detected in both HCC and cirrhosis. This study constitutes the first comprehensive study of P gp, AFP, and endothelial markers in canine HCC and cirrhosis. The importance of these markers in HCC and cirrhosis in dogs was demonstrated and provides a more accurate basis for a definitive diagnosis of HCC and cirrhosis in dogs. PMID- 17846233 TI - The spectrum of canine cutaneous perivascular wall tumors: morphologic, phenotypic and clinical characterization. AB - Perivascular wall tumors (PWTs) are defined as neoplasms deriving from mural cells of blood vessels, excluding the endothelial lining. The spectrum of human cutaneous PWT includes glomus tumor, hemangiopericytoma (HEP), myopericytoma, angioleiomyoma/sarcoma, angiomyofibroblastoma, and angiofibroma. The purpose of this study was to revise clinical presentation, cytology, histopathology, and immunohistology of canine cutaneous PWT with cytology typical of canine HEP. Diagnosis was established on the basis of vascular growth patterns (staghorn, placentoid, perivascular whorling, bundles from media) and immunohistology, including 7 smooth muscle markers and the cell membrane ganglioside of unknown origin recognized by the antibody 3G5 (CMG-3G5). Twenty cases were included. Ages ranged from 6 to 13 years; 12 dogs were males and 8 were females, and there was a prevalence of crossbreeds. Tumors arose from a single site with preferential acral location (10/20). Cytology revealed moderate to high cellularity in all cases, cohesive groups of cells (19/20), capillaries (18/20), and bi- to multinucleated cells (18/20). Six myopericytomas, 5 angioleiomyomas, 2 angioleiomyosarcomas, 2 HEP, 1 angiofibroma, and 1 adventitial tumor were identified. A definitive diagnosis was not possible in 3 cases. Smoothelin, heavy caldesmon, desmin, myosin, calponin, and CMG-3G5 were the most valuable markers to differentially diagnose canine PWT. Similar to reports in humans, canine HEP embodied a spectrum of neoplastic entities arising from different vascular mural cells. Before canine PWTs are assimilated into one prognostic category, a consistent classification and characterization of their biology is necessary. As proposed in humans, HEP should also be considered a diagnosis of exclusion in dogs. PMID- 17846234 TI - Porcine circovirus type 2-associated cerebellar vasculitis in postweaning multisystemic wasting syndrome (PMWS)-affected pigs. AB - Porcine circovirus type 2 (PCV2) is associated with several syndromes in growing pigs, including postweaning multisystemic wasting syndrome and porcine dermatitis and nephropathy syndrome. In the present study, a previously undescribed neurovascular disorder associated with a PCV2 infection is described. Sixteen pigs showed clinical signs of wasting and neurologic deficits. Acute hemorrhages and edema of cerebellar meninges and parenchyma due to a necrotizing vasculitis resulted in degeneration and necrosis of the gray and white matter. Few to numerous PCV2 DNA and antigen-bearing endothelial cells were detected in affected areas of the brain using in situ hybridization and immunohistochemistry. Conventional histochemical stains, as well as the detection of caspase 3 activity and DNA strand breaks by the terminal transferase dUTP nick end labeling assay, showed numerous apoptotic endothelial cells in the vascular lesions observed. Sequencing of various brain-derived PCV2-specific amplicons revealed a strong identity between different isolates and an 89 to 100% identity to previous isolates. The phylogenetic tree showed that there was no clustering of isolates correlating to clinical signs or geographic distribution. This previously undescribed PCV2-associated neurologic disease has features of both postweaning multisystemic wasting syndrome and, to a lesser extent, porcine dermatitis and nephropathy syndrome. The available evidence suggests that direct virus-induced apoptosis of endothelial cells plays a role in the pathogenesis of this unusual PCV2-associated cerebellar vasculitis. PMID- 17846235 TI - Pathologic findings of highly pathogenic avian influenza virus A/Duck/Vietnam/12/05 (H5N1) in experimentally infected pekin ducks, based on immunohistochemistry and in situ hybridization. AB - The ongoing H5N1 Asian epidemic is currently affecting a number of avian species including ducks. These birds are an important part of the poultry industry in the affected countries, and it is likely that they are acting as a reservoir of infection. Ten Pekin ducks were challenged with 100 microl containing 10(7) 50% egg infective dose of the highly pathogenic avian influenza virus (HPAIV) A/Duck/Vietnam/12/05 (H5N1), administered by an intra-nasal and oral route. Clinical symptoms were recorded twice a day up to 14 days postinfection (dpi). Clinical signs were first noted at 2 dpi, with conjunctivitis and slight depression, and progressed over a period of 1-3 days to severe neurologic signs consisting of torticollis, incoordination, tremors, and seizures. Survival times varied from 3 to 7 dpi. On postmortem examination, hemorrhages were observed in the duodenum, ceca, proventriculus, ventriculus, trachea, pancreas, and brain. Histologic lesions, as well as immunohistochemistry positivity, were recorded in the pancreas and brain. In situ hybridization revealed viral antigen associated with acinar pancreatic cells, bronchial epithelial cells, and with cells of the central nervous system as well as neurons of the submucosal plexus of the duodenum. Our experimental findings agree with those previously observed in ducks naturally infected with HPAIV H5N1 viruses, confirming the acquired viral neurotropism and pancreatotropism, as previously noted in other avian species, as well as in humans. PMID- 17846236 TI - Distribution and cellular heterogeneity of bovine viral diarrhea viral antigen expression in the brain of persistently infected calves: a new perspective. AB - Persistent infection following in utero exposure to bovine viral diarrhea virus (BVDV) early in gestation is a serious cause of morbidity and mortality in cattle industries worldwide. The brain is a primary target of persistent infection. In the current study, the types of cells infected and topography of viral antigen expression were examined in brain sections from 9 BVDV persistently infected crossbred calves, all less than 1 year of age, by immunohistochemical staining using the 15C5 primary monoclonal antibody. BVDV antigen was detected in the brains of all persistently infected calves. A variety of cell types was infected, including neurons, astrocytes, oligodendroglia, blood vessel-associated cells (pericytes, perivascular macrophages, smooth muscle cells), and cells in the leptomeninges (blood vessel-associated cells). Conclusive demonstration of viral antigen in vascular endothelial cells was elusive. The intensity and distribution of viral antigen staining in neurons were highly variable. Viral antigen staining was most consistent and intense in thalamic nuclei, most notably in dorsal and medial nuclear groups, followed by the hippocampus, entorhinal cortex, basal nuclei, and piriform cortex. Staining in other brain areas was often less intense and inconsistent. The variability in the intensity and topography of viral antigen in the brain may explain the heterogeneity in the clinical manifestations of BVDV-induced disease. Additionally, infection of the brain in persistently infected calves may underlie or at least contribute to endocrine disturbances and immunologic deficits that are protean manifestations of BVDV-induced disease. PMID- 17846237 TI - Intra-nasal inoculation of American bison (Bison bison) with ovine herpesvirus-2 (OvHV-2) reliably reproduces malignant catarrhal fever. AB - Sheep-associated malignant catarrhal fever (MCF) due to infection with ovine herpesvirus 2 (OvHV-2) is common in commercial herds of American bison ( Bison bison). Inability to propagate OvHV-2 in vitro has been a constraint on experimental studies of the disease. We sought to establish whether nasal secretions from sheep that shed OvHV-2 might induce the disease in bison and to define a minimum challenge dose. Fourteen bison were nebulized with sheep nasal sections containing 10(3)-10(7) OvHV-2 deoxyribonucleic acid (DNA) copies. Most challenged bison (11/14, 78.6%) developed clinical signs at 29-52 days postnebulization (DPN). The mean incubation time was 42.18 (+/-7.33 SD) DPN. Using real-time polymerase chain reaction, we detected OvHV-2 DNA in peripheral blood leukocytes at 21-31 DPN. All bison that developed MCF had antibodies against the MCF group viruses. Gross and histologic lesions were typical of the acute disease. There was no morphologic evidence of a dose-related difference in the severity or distribution of lesions. This is the first successful reproduction of MCF in bison using a nasal route of exposure. Experimentally challenged bison are more susceptible to MCF, compared with experimentally challenged domestic cattle in a previous experiment. Bison are a pertinent ruminant species in which the pathogenesis of the disease can be investigated. PMID- 17846238 TI - Ultrastructural examination of the host cellular response in the gills of Atlantic salmon, Salmo salar, with amoebic gill disease. AB - Gills from Atlantic salmon with experimentally induced amoebic gill disease (Neoparamoeba spp.) were examined with transmission electron microscopy to assess pathology and host-cell responses. Amoebae were found either on the surface epithelium or with pseudopodia extending deeply into invaginations of epithelial cells. The amoebae had various densities along the plasma membrane and contained electron-dense deposits within their cytoplasm. Surface epithelial cells sloughed from the gills and had features consistent with apoptosis, including rounded shape, loss of surface microridges, and hypercondensation of nuclear chromatin. Affected areas of gills had fusion of secondary lamellae with interlamellar spaces occupied by mitotic epithelial cells and eosinophils. Eosinophils contained abundant fusiform-shaped granules that measured approximately 1 microm long and 360 nm wide. The granule consisted of an electron-dense matrix with a central inclusion that was less electron-dense, consisting of particulate and fibrillar material. In many instances, the central inclusion appeared empty and 90% of the eosinophils had morphology suggestive of piecemeal degranulation. Also observed within affected areas were a few neutrophils, mucous cells releasing mucus, and a small number of dendritic-like cells. PMID- 17846239 TI - Metastatic iridociliary adenocarcinoma in a labrador retriever. AB - An enucleated left eye from a 15-year-old female spayed Labrador Retriever was received by the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) for histopathologic evaluation. Routine histologic preparation included staining with hematoxylin and eosin, and with alcian blue periodic acid-Schiff (PAS). At necropsy 9 months later, all grossly abnormal tissues (ipsilateral orbit and lung) were submitted to the COPLOW for histopathologic evaluation. Histopathologic evaluation of the globe revealed extensive invasion of the uvea and sclera by a pleomorphic cell population that formed disorganized cords and exhibited PAS-positive basement membrane material. Necropsy revealed a morphologically similar tumor in the ipsilateral orbit and lung. On immunohistochemical examination, the intraocular tumor stained diffusely immunopositive for vimentin, S-100, and neuron-specific enolase and multifocally, sparsely immunopositive for cytokeratin AE1/AE3. The orbital and thoracic tumors stained positively for vimentin but negatively for cytokeratin AE1/AE3. There are few reports of canine metastatic iridociliary adenocarcinoma in the literature; this is the first with immunohistochemical analysis. PMID- 17846240 TI - Immunohistochemical characterization and evaluation of prognostic factors in canine oral melanomas with osteocartilaginous differentiation. AB - Melanomas are the most common malignant oral neoplasm in dogs. Osteocartilaginous differentiation in oral melanomas is a rare feature described both in veterinary and human medicine. Here, 10 cases of this type of neoplasm were used to study their immunohistochemical, biological, and clinical characteristics. Reactivity for S100 and melan A antigen was evaluated, and 4 prognosis factors (mitotic index, invasiveness of epithelium, nuclear atypia, and proliferation index) were analyzed and correlated with the clinical course of the neoplasms after diagnosis. Immunohistochemical analysis of the studied neoplasms, including the osteocartilaginous areas, showed positive immunoreaction for S100 and melan A, except in one dog, which was negative for melan A. Analysis of the results showed that oral melamonas with osteocartilaginous differentiation have a clinical course similar to that of other melanomas in the oral cavity. Analysis of the mitotic index and the expression of proliferation marker Ki-67 could be useful tools for predicting the biological behavior of these neoplasms. PMID- 17846241 TI - Cutaneous toxoplasmosis in a female Japanese cat. AB - A 16-year-old female Japanese cat was presented with a single mammary-gland nodule approximately 3 cm in diameter. Histologically, the nodule consisted of necrotizing granulomatous panniculitis, vasculitis, and mastitis, and contained free and clustered protozoal organisms. The organism was present in the cytoplasm of macrophages, fibroblasts, endothelial cells, and mammary-gland epithelia. The organism was positive for anti- Toxoplasma gondii and anti- Neospora caninum antibodies. Electron microscopy showed single and grouped tachyzoites, with morphologic features similar to those of T. gondii. Polymerase chain reaction and deoxyribonucleic acid sequence analysis was consistent with T. gondii infection. This is the first report of cutaneous toxoplasmosis in a Japanese cat. PMID- 17846242 TI - Aleutian disease in two domestic striped skunks (Mephitis mephitis). AB - This report describes the use of polymerase chain reaction and DNA in situ hybridization to diagnose Aleutian mink disease parvovirus DNA in various tissue specimens from 2 companion striped skunks. Clinical, laboratory, and microscopic findings also support a clinical diagnosis of Aleutian disease in these mink. PMID- 17846243 TI - Spontaneous osteosarcoma in a rabbit ( Oryctolagus cuniculus). AB - A 6-year-old male cross-breed rabbit ( Oryctolagus cuniculus) was presented with lameness and severe swelling from the right shoulder to brachium. On 16-detector helical computed tomography images of the amputated right forelimb after being fixed in formalin, evident proliferative and destructive lesions of bone were observed. On histologic examination, the tumor was composed of proliferating neoplastic cells that resembled histiocytes, with abundant osteoid production. A large number of multinucleated giant cells were found throughout. This case was diagnosed as osteosarcoma by clinical, radiographic, and histologic findings. This is a rare case report of osteosarcoma in a rabbit consistent with canine predilection sites. PMID- 17846244 TI - Chronic polymyositis associated with disseminated Sarcocystosis in a captive-born rhesus macaque. AB - A 2-year-old, captive-born, clinically healthy male, rhesus macaque, was euthanatized as part of an experimental study. At necropsy, diffuse pale streaking of the trunk, lumbar, and limb muscles were noted macroscopically. On histology, numerous elongated cysts that contained crescent-shaped basophilic spores were found in the fibers of skeletal muscles. Scattered affected myofibers were degenerate and accompanied by eosinophilic-to-granulomatous inflammation. Sarcocysts had prominent villus-like projections with the morphology of a type 11 sarcocyst wall similar to Sarcocystis neurona but possessing many more villus microtubules than is reported for S. neurona. In addition, bradyzoites were very long, up to approximately 12 microm in length. The protozoa were consistent with a Sarcocystis sp., based on histology and ultrastructure, however, a definitive identification of the species was not possible. Nonspecific immunohistochemical crossreaction with Sarcocystis cruzi antisera was observed. The 18S ribosomal deoxyribonucleic acid sequence showed 91% similarity to Sarcocystis hominis, 90% similarity to Sarcocystis buffalonis, and 89% similarity to Sarcocystis hirsuta. Interestingly, the ITS1 sequence showed very little homology to any sequence in GenBank, suggesting that this is possibly a unique Sarcocystis sp. Sarcocystosis is often considered an incidental finding, particularly in wild-caught animals, with little clinical significance. However, as demonstrated in this report and others, disseminated sarcocystosis can occur in captive-born rhesus macaques with or without clinical signs. In some cases interference with research results can occur; including death in fulminant cases. PMID- 17846245 TI - Histopathologic evidence of capecitabine corneal toxicity in dogs. AB - In an experimental model of transplant rejection, renal transplants were performed on 6 mixed-breed dogs. Capecitabine (CPC) was administered as an oral immunosuppressive agent. All recipients received systemic CPC, cyclosporine (CSA), prednisolone, and famotidine throughout the study. Two dogs developed superficial keratitis, which was characterized by multifocal geographic erosions, superficial corneal epithelial pigmentation, and corneal neovascularization. These clinical signs correlated with the dose of CPC given, whereas other drug doses remained unchanged. After euthanasia, routine histologic sections were stained with hematoxylin and eosin and with alcian blue periodic acid-Schiff for light microscopic evaluation. Ocular histopathologic abnormalities were limited to neovascularization and inflammatory infiltrate of the anterior corneal stroma and abnormal basal cell morphology, disorganization, thinning, and pigmentation of the corneal epithelium. The purpose of this communication is to describe the clinical and histopathologic evidence of CPC corneal toxicity in dogs. PMID- 17846246 TI - Spontaneously occurring alimentary osteofluorosis associated with proliferative gastroduodenopathy in rabbits. AB - Growing rabbits from two rabbitries, fed with commercial concentrates and hay, developed painful thickenings of the extremities. Four rabbits from each farm were clinically examined and necropsied. All animals showed multiple moderate to severe osseous proliferations of extremities and mandibles and a mild to severe proliferative gastroduodenopathy. Histologically, periosteal and endosteal hyperostosis and a mild to severe proliferation of the gastric and duodenal mucosa were noted. Bone analyses revealed 12,700 and 15,000 microg fluoride per gram of bone ash in affected rabbits, compared with 550 microg fluoride in a control animal. A highly elevated fluoride content was found in concentrates. Vitamin A levels were moderately increased only in one concentrate, and copper levels were normal. Results indicate that alimentary fluoride intoxication caused prominent bony proliferations in the examined rabbits. Whether the proliferative gastroduodenopathy is related to the elevated fluoride intake or represents an incidentally occurring secondary disease remains to be determined. PMID- 17846247 TI - Multiple hepatic peribiliary cysts in a young pig. AB - Histopathologic features of hepatic peribiliary cysts were described in a young slaughtered pig. The animal was an apparently healthy 6-month-old pig of mixed breed. Macroscopically, all lobes of the liver contained numerous cysts of varying size containing serous fluid in all lobes. Histopathologically, the cysts were located mainly around the large bile duct and in the connective tissue of the portal tracts. Within serial sections, these cysts were assumed to be solitary or multilocular, but they were separated from the bile duct. The cysts were lined by a single layer of columnar, cuboidal, and flattened epithelial cells. Occasionally, goblet cells were observed. The epithelial cells were stained with periodic acid-Schiff/alcian blue and high-iron diamine/alcian blue, indicating the presence of neutral mucin, sialomucin, and sulfomucin. Grimalius' method revealed the presence of endocrine cells in the lining epithelium. There was no bile pigment in the cysts by the Hall method. PMID- 17846248 TI - Bronchioloalveolar carcinoma not related to jaagsiekte sheep retrovirus in a goat. AB - A spontaneous lung tumor in a 5-year-old goat of the Murciano-Granadina breed is described in this paper. Clinical signs of cachexia and tachypnoea were evident, and a considerable amount of white mucous foamy fluid was discharged from the nostrils when the animal's head was lowered. A lung tumor with the characteristics of bronchioloalveolar carcinoma was detected during histopathologic examination. The tumor cells were positive for surfactant proteins C and B, confirming that alveolar type II cells were the origin of the neoplasia. Tumor samples were tested by polymerase chain reaction, immunoblotting, and immunohistochemistry for the presence of Jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV), another retrovirus very closely related to JSRV, but all tests were negative. Therefore, this is the first reported case of spontaneous bronchioloalveolar carcinoma not related to JSRV or ENTV infection in a goat. PMID- 17846249 TI - Internal hydrocephalus and associated periventricular encephalitis in a young fox. AB - Marked lateral ventricular enlargement associated with atrophic cerebral cortex and periventricular encephalitis is described in a 2-month-old fox affected by disorientation, generalized ataxia, difficulty in walking, circling, and blindness. Clinical conditions progressed to stupor and spontaneous death within a few days. At necropsy, severe inflammatory and necrotizing lesions were observed in periventricular sites associated with diverticula and cleft formation in perithalamic areas and rhinencephalic cortex. Immunolabeling for Toxoplasma gondii, Neospora caninum, Encephalitozoon cuniculi, canine distemper virus, and rabies virus was negative. Given the presence of periventricular and choroidal neutrophilic/mononuclear cell infiltration, it is thought that a bacterial infection may have been the cause of the inflammatory lesions, with internal hydrocephalus secondary to the severe periventricular lesions. A similar condition has been previously reported in the pathogenesis of spontaneously occurring acquired canine hydrocephalus, but no viral or bacterial causes have been investigated to date. PMID- 17846250 TI - Pathology of inhalational anthrax infection in the african green monkey. AB - There is a critical need for an alternative nonhuman primate model for inhalational anthrax infection because of the increasingly limited supply and cost of the current model. This report describes the pathology in 12 African green monkeys (AGMs) that succumbed to inhalational anthrax after exposure to a low dose (presented dose 200-2 x 10(4)colony-forming units [cfu]) or a high dose (presented dose 2 x 10(4)-1 x 10(7) cfu) of Bacillus anthracis (Ames strain) spores. Frequent gross lesions noted in the AGM were hemorrhage and edema in the lung, mediastinum, and mediastinal lymph nodes; pleural and pericardial effusions; meningitis; and gastrointestinal congestion and hemorrhage. Histopathologic findings included necrohemorrhagic lymphadenitis of mediastinal, axillary, inguinal, and mesenteric lymph nodes; mediastinal edema; necrotizing splenitis; meningitis; and congestion, hemorrhage, and edema of the lung, mesentery, mesenteric lymph nodes, gastrointestinal tract, and gonads. Pathologic changes in AGMs were remarkably similar to what has been reported in rhesus macaques and humans that succumbed to inhalational anthrax; thus, AGMs could serve as useful models for inhalation anthrax studies. PMID- 17846251 TI - Omental leiomyoma in a male adult horse. AB - A well-circumscribed mass 70 x 35 x 28 cm in size and 41 kg in weight was detected at necropsy in a male adult horse within the omentum major without any association to the gastrointestinal tract. The tumor consisted of multiple white to-yellow lobules and displayed a firm consistency. In addition, multiple cysts filled with blood-like fluid, and multifocal areas of necrosis were observed. Histologically, the mass consisted of slightly pleomorphic spindloid-shaped cells arranged in interlacing bundles containing elongated nuclei with blunt ends. The majority of tumor cells revealed a positive immunoreaction for alpha-smooth muscle actin, vimentin, and neuron-specific enolase and were negative for S-100, factor VIII-related antigen, and glial fibrillary acidic protein. Few tumor cells showed expression of desmin and c-kit. On the basis of macroscopy, histology, and immunohistochemistry, an omental leiomyoma was diagnosed. PMID- 17846254 TI - Doubts about quantal analysis. PMID- 17846256 TI - Anabolic androgenic steroids induce region- and subunit-specific rapid modulation of GABA A receptor-mediated currents in the rat forebrain. PMID- 17846257 TI - Association between mortality and cognitive change over 7 years in a large representative sample of UK residents. AB - OBJECTIVE: To examine the association between change in reaction time and cognitive performance over 7 years and the risk of death from all causes and some specific causes after controlling for known risk factors. METHODS: The sample comprised members of the Health and Lifestyle Survey (HALS) of community-dwelling adults in England, Scotland, and Wales. Baseline testing (HALS1), involving 9003 people, took place in 1985 and 1986. Sociodemographic, lifestyle, health, and physiological information was collected. Cognitive functioning was measured using tests of simple and choice reaction time, a short memory test, and a test of visual-spatial reasoning. Follow-up testing (HALS2) took place in 1991 and 1992, when 5352 members of the study were administered the same questionnaires, physiological examinations, and cognitive tests. The sample has been followed for mortality up to June 2005. RESULTS: After controlling for age, gender, and the relevant baseline cognitive test scores, greater declines between HALS1 and HALS2 on simple reaction time mean and variability, choice reaction time mean and variability, memory and visual-spatial reasoning were associated with significantly increased risks of death from all causes, all cardiovascular diseases (CVDs), coronary heart disease (CHD), stroke, and respiratory disease. These associations were only slightly attenuated after adjusting for occupational social class, educational, smoking, alcohol consumption, physical activity, body mass index, blood pressure, and lung function. CONCLUSIONS: Decline in performance of reaction times and simple cognitive tasks across a 7-year period was associated with an increased risk of death from all causes, all CVDs, CHD, stroke, and respiratory disease up to 13 years later, even after adjustment for known risk factors. PMID- 17846258 TI - Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine. AB - OBJECTIVE: To examine the antidepressant efficacy of a dual-acting antidepressant (mirtazapine) in patients with post-myocardial infarction (MI) depressive disorder. Antidepressants used in post MI trials with a randomized, double-blind, placebo-controlled design have been restricted to selective serotonin reuptake inhibitors (SSRIs). Antidepressant effects have been limited. METHODS: In a prospective multicenter study, 2177 patients with MI were evaluated for depressive disorder during the first year post MI. Ninety-one patients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for major or minor depressive disorder were randomized to a 24-week, double-blind, placebo-controlled trial. Antidepressant efficacy was tested using last-observation-carried-forward procedure and repeated measurements analysis using the SPPS mixed models approach, with as primary outcome reduction in depressive symptomatology on the 17-item Hamilton-Depression Rating Scale (Ham D), and secondary outcomes the Beck Depression Inventory (BDI) and depression subscale of the Symptom Check List 90 items (dSCL-90) as well as the Clinical Global Impression (CGI) scale. RESULTS: Using the "last observation carried forward" (LOCF) method, mirtazapine did not show to be superior to placebo on the Ham-D, but did on the BDI, dSCL-90, and CGI scale over the acute treatment phase of 8 weeks (n = 91). Using mixed models analysis over the entire 24 weeks of treatment (n = 40), we did find a significant difference favoring mirtazapine to placebo on the Ham-D, BDI, and CGI, but on the dSCL-90, this difference was not significant. CONCLUSIONS: This trial shows efficacy of mirtazapine on primary and secondary depression measures. Mirtazapine seems to be safe in the treatment of post-MI depression. PMID- 17846260 TI - Efficacy and safety of tadalafil in men with erectile dysfunction following spinal cord injury. AB - OBJECTIVE: To determine the efficacy and safety of tadalafil when taken on demand by men with erectile dysfunction (ED) secondary to traumatic spinal cord injury (SCI). DESIGN AND SETTING: Multicenter, randomized, double-blind, placebo controlled, flexible dose-titration, parallel-group study in clinical practices in Europe. Patients Enrolled patients had ED secondary to SCI (all spinal levels) and sustained 6 months or longer before visit 1. INTERVENTIONS: After a 4-week run-in period, patients were randomly assigned to tadalafil, 10 mg, (n = 142) or placebo (n = 44) for a 12-week, on-demand treatment period with assessments at 4 week intervals. The dose of tadalafil was maintained or titrated (10 or 20 mg) at 4 and 8 weeks. MAIN OUTCOME MEASURES: Efficacy was measured using the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and Global Assessment Question (GAQ). Treatment-emergent adverse events and vital signs were collected at each visit. RESULTS: Mean age was 38 years. Mean baseline IIEF erectile function domain score was 13.4, and following 12 weeks of treatment, 22.6 for tadalafil and 13.6 for placebo (P < .001). After treatment, the tadalafil group compared with the placebo group was significantly greater (P < .001) in mean per-patient percentage of successful penetration attempts (SEP question 2; 75.4% vs 41.1%) and intercourse attempts (SEP question 3; 47.6% vs 16.8%); percentage of improved erections (GAQ question 1; 84.6% vs 19.5%); and ejaculatory frequency (IIEF question 9; P = .03). The 2 most common treatment emergent adverse events in the tadalafil group compared with placebo were headache (8.5% vs 4.5%) and urinary tract infection (7.7% vs 6.8%). CONCLUSIONS: Tadalafil (10 mg and 20 mg) improved erectile function and was well tolerated by men with ED secondary to traumatic SCI. PMID- 17846261 TI - New techniques for imaging Human Immunodeficiency Virus associated cognitive impairment in the era of highly active antiretroviral therapy. PMID- 17846259 TI - Exercise and pharmacotherapy in the treatment of major depressive disorder. AB - OBJECTIVE: To assess whether patients receiving aerobic exercise training performed either at home or in a supervised group setting achieve reductions in depression comparable to standard antidepressant medication (sertraline) and greater reductions in depression compared to placebo controls. METHODS: Between October 2000 and November 2005, we performed a prospective, randomized controlled trial (SMILE study) with allocation concealment and blinded outcome assessment in a tertiary care teaching hospital. A total of 202 adults (153 women; 49 men) diagnosed with major depression were assigned randomly to one of four conditions: supervised exercise in a group setting; home-based exercise; antidepressant medication (sertraline, 50-200 mg daily); or placebo pill for 16 weeks. Patients underwent the structured clinical interview for depression and completed the Hamilton Depression Rating Scale (HAM-D). RESULTS: After 4 months of treatment, 41% of the participants achieved remission, defined as no longer meeting the criteria for major depressive disorder (MDD) and a HAM-D score of <8. Patients receiving active treatments tended to have higher remission rates than the placebo controls: supervised exercise = 45%; home-based exercise = 40%; medication = 47%; placebo = 31% (p = .057). All treatment groups had lower HAM-D scores after treatment; scores for the active treatment groups were not significantly different from the placebo group (p = .23). CONCLUSIONS: The efficacy of exercise in patients seems generally comparable with patients receiving antidepressant medication and both tend to be better than the placebo in patients with MDD. Placebo response rates were high, suggesting that a considerable portion of the therapeutic response is determined by patient expectations, ongoing symptom monitoring, attention, and other nonspecific factors. PMID- 17846262 TI - Gene therapy for duchenne muscular dystrophy: expectations and challenges. AB - Duchenne muscular dystrophy is a debilitating X-linked disease with limited treatment options. We examined the possibility of moving forward with gene therapy, an approach that demonstrates promise for treating Duchenne muscular dystrophy. Gene therapy is not limited to replacement of defective genes but also includes strategies using surrogate genes with alternative but effective means of improving cellular function or repairing gene mutations. The first viral-mediated gene transfer for any muscle disease was carried out at Columbus Children's Research Institute and Ohio State University for limb girdle muscular dystrophy type 2D, and the first viral-mediated trial of gene transfer for Duchenne muscular dystrophy is under way at the same institutions. These studies, consisting of intramuscular injection of virus into a single muscle, are limited in scope and represent phase 1 clinical trials with safety as the primary end point. These initial clinical studies lay the foundation for future studies, providing important information about dosing, immunogenicity, and viral serotype in humans. This article highlights the challenges and potential pitfalls as the field advances this treatment modality to clinical reality. PMID- 17846263 TI - The relationship of Parkinson disease with aging. AB - Twentieth-century hypotheses attributing a substantive role to aging in Parkinson disease (PD) pathogenesis have been countered by evidence from clinical, pathological, and biochemical investigations. However, age influences the clinical progression of PD. Several studies have demonstrated that advancing age is associated with a faster rate of motor progression, decreased levodopa responsiveness, more severe gait and postural impairment, and more severe cognitive impairment and the development of dementia in patients with PD. A model for the relationship between PD and aging is proposed that incorporates the following 3 elements: (1) There occurs a superposition of a topographic gradient of neuronal loss in brainstem and basal forebrain structures related to the disease process and an aging-related temporal gradient. (2) While PD is a chronic progressive disorder, the most important determinant of clinical progression is advancing age rather than disease duration. (3) The effects of the disease process and aging on nondopaminergic structures involve a biologic interaction. The model implies that understanding the degenerative process in nondopaminergic structures in PD as it relates to molecular mechanisms accompanying the aging of the nervous system may create opportunities for interventions affecting the clinical progression of the disease. PMID- 17846264 TI - Platelet decline: an avenue for investigation into the pathogenesis of human immunodeficiency virus -associated dementia. AB - BACKGROUND: The identification of biomarkers identifying onset of human immunodeficiency virus-associated dementia (HIV-D) is critical for diagnosis and the elucidation of pathophysiologic pathways. OBJECTIVE: To examine the association between platelet decline from baseline and HIV-D. DESIGN: Prospective cohort study within the North-East AIDS Dementia cohort. SETTING: Four participating referral centers in the United States. PARTICIPANTS: A total of 396 subjects with advanced human immunodeficiency virus (HIV) infection recruited between 1998 and 2003 and undergoing serial neurologic assessments. Eligibility criteria required CD4 cell counts less than 200/microL or less than 300/microL with evidence of cognitive impairment. A cohort subset without prevalent HIV-D at baseline and without incident HIV-D at the visit immediately after baseline was analyzed (n = 146). Main Outcome Measure Time to first diagnosis of HIV-D. RESULTS: After a median follow-up of 31.1 months, 40 subjects developed HIV-D. Platelet decline from baseline was associated with the development of HIV-D when examined as a time-dependent variable lagged by 6 to 12 months before outcome (multivariate hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.14-5.02; P = .02). This association was stronger during the first 2 years of follow-up (multivariate HR, 6.76; 95% CI, 2.36-19.41; P < .001) than during later years (multivariate HR, 0.94; 95% CI, 0.33-2.67; P = .90). CONCLUSIONS: These results suggest that individuals with declining platelet counts are at greater risk for HIV-D and that the dynamics of circulating platelets vary with respect to the temporal progression of HIV-D. This highlights an avenue to be explored in the understanding of HIV-D pathogenesis. PMID- 17846265 TI - Putamen hypertrophy in nondemented patients with human immunodeficiency virus infection and cognitive compromise. AB - BACKGROUND: Documented death and dysfunction of basal ganglia cells in patients seropositive for human immunodeficiency virus (HIV) suggest that the virus may cause structural compromise to these regions. OBJECTIVES: To examine subcortical volumes in nondemented patients seropositive for HIV (HIV+) by means of a novel automated neuroanatomic morphometric analysis tool, and to investigate relationships among cognitive function, immune health, and subcortical volumes. DESIGN AND SETTING: Cross-sectional study of subcortical morphometry and cognitive function conducted at the Boston University Center for Memory and Brain and the Massachusetts General Hospital Athinoula A. Martinos Center for Biomedical Imaging. PATIENTS: Twenty-two nondemented HIV+ patients and 22 age- and education-matched healthy control participants. MAIN OUTCOME MEASURES: Subcortical segmentation volumes, neuropsychological performance, and immunological variables. RESULTS: Nondemented HIV+ patients demonstrated relative and isolated putamen hypertrophy compared with control participants. Putamen volume enlargement in HIV+ patients was related to motor slowing and immune status, such that higher CD4 lymphocyte levels were associated with larger putamen volumes. There were no other subcortical volume differences between the groups. CONCLUSIONS: This study suggests that basal ganglia hypertrophy accompanies HIV-related mild cognitive compromise. These findings may represent a structural imaging parallel to functional imaging studies demonstrating basal ganglia hypermetabolism in HIV+ patients with mild cognitive compromise and early HIV-associated brain disease. PMID- 17846266 TI - Acute deep-brain stimulation of the internal and external globus pallidus in primary dystonia: functional mapping of the pallidum. AB - BACKGROUND: Dystonia is a syndrome characterized by prolonged muscle contractions that cause sustained twisting movements and abnormal posturing of body parts. Patients with the severe and generalized forms can benefit from bilateral high frequency pallidal stimulation. OBJECTIVE: To investigate the functional map of the globus pallidus (GP) in patients with primary generalized dystonia. DESIGN: Prospective multicenter, double-blind, video-controlled study in patients treated at a university hospital. SETTING: University secondary care centers. PATIENTS: Twenty-two patients with primary generalized dystonia. INTERVENTIONS: Acute internal and external pallidal deep-brain stimulation or pallidal deep-brain stimulation. MAIN OUTCOME MEASURES: The clinical effects of acute bilateral high frequency ventral vs acute dorsal pallidal stimulation were assessed with the Movement subscale of the Burke-Fahn-Marsden Dystonia Rating Scale. Intrapallidal localization of the contacts of the quadripolar electrodes was performed using a 3-dimensional atlas-magnetic resonance imaging coregistration method by investigators blinded to the clinical outcome. RESULTS: Bilateral acute ventral stimulation of the GP significantly improved the Burke-Fahn-Marsden Dystonia Rating Scale score by 42% and resulted in stimulation of contacts located in the internal GP or medullary lamina in 18 of 21 patients. Bilateral acute dorsal pallidal stimulation, primarily localized within the external GP, had variable effects across patients, with half demonstrating slight or no improvement or even aggravation of dystonia compared with baseline. CONCLUSIONS: Ventral pallidal stimulation, primarily of the internal GP or medullary lamina or both, is the optimal method for the treatment of dystonia. The varying effects across patients of bilateral acute dorsal pallidal stimulation, primarily of the external GP, suggest that unknown factors associated with dystonia could have a role in and contribute to the effects of the electrical stimulation. PMID- 17846267 TI - Association of higher serum calcium levels with smaller infarct volumes in acute ischemic stroke. AB - BACKGROUND: Elevated serum calcium levels at admission in patients with stroke have been associated with less severe clinical deficits and with better outcomes; however, the relationship between serum calcium levels and volumetric measurement of cerebral infarct size on neuroimaging has not been studied, to our knowledge. OBJECTIVE: To assess the relationship between serum calcium levels at admission and initial diffusion-weighted magnetic resonance imaging (DWI) infarct volumes among patients with acute ischemic stroke. DESIGN: Secondary analysis of prospectively collected hospital quality improvement data. SETTING: Tertiary university hospital. PATIENTS: One hundred seventy-three consecutive patients with acute ischemic stroke initially seen within 24 hours of the last known well time. MAIN OUTCOME MEASURES: Total serum calcium levels were measured on admission and were collapsed into quartiles. The DWI lesions were outlined using a semiautomated threshold technique. The relationship between serum calcium level quartiles and DWI infarct volumes was examined using multivariate quartile regression analysis. RESULTS: One hundred seventy-three patients (mean age, 70.3 years [age range, 24-100 years]; median National Institutes of Health Stroke Scale score, 4 [range, 0-38]) met the study criteria. The median DWI infarct volumes for the serum calcium level quartiles (lowest to highest quartile) were 9.42, 2.11, 1.03, and 3.68 mL. The median DWI infarct volume in the lowest serum calcium level quartile was larger than that in the other 3 quartiles (P < .005). After multivariate analysis, the median adjusted DWI infarct volumes for the serum calcium level quartiles (lowest to highest) were 8.9, 5.8, 4.5, and 3.8 mL. The median adjusted DWI infarct volume in the lowest serum calcium level quartile was statistically significantly larger than that in the other 3 quartiles (P < .05). CONCLUSIONS: Higher serum calcium levels at admission are associated with smaller cerebral infarct volumes among patients with acute ischemic stroke. These results suggest that serum calcium level may serve as a clinical prognosticator following stroke and may be a potential therapeutic target for improving stroke outcome. PMID- 17846269 TI - Associations between cervical cord gray matter damage and disability in patients with multiple sclerosis. AB - OBJECTIVES: To assess in vivo the volume and the magnetization transfer magnetic resonance imaging (MRI)-detectable damage of the cervical cord gray matter in patients with relapsing-remitting multiple sclerosis (RRMS) and to evaluate whether such damage correlates with disability. DESIGN: Cervical cord conventional and magnetization transfer MRI scans were acquired from 18 patients with RRMS (and no T2-visible cervical cord lesions) and 13 age- and sex-matched healthy controls. After ad hoc image postprocessing, characterized by high intraobserver reproducibility, the average magnetization transfer ratio and volume of the cervical cord gray matter from patients and controls were calculated and compared using a 2-tailed t test with Bonferroni correction. The correlation between MRI metrics and Expanded Disability Status Scale score was assessed using the Spearman rank correlation coefficient. RESULTS: Compared with healthy controls, patients with RRMS had a lower cervical cord gray matter average magnetization transfer ratio (P = .009). No cervical cord gray matter atrophy was detected. In patients with RRMS, the gray matter average magnetization transfer ratio was correlated with the degree of disability (r = 0.48, P = .048). CONCLUSIONS: Cervical cord gray matter is not spared by MS pathology, and such damage is an additional factor contributing to the disability of these patients. PMID- 17846268 TI - Magnetic resonance imaging effects of interferon beta-1b in the BENEFIT study: integrated 2-year results. AB - BACKGROUND: In the Betaseron/Betaferon in Newly Emerging Multiple Sclerosis for Initial Treatment (BENEFIT) study, interferon beta-1b delayed conversion to multiple sclerosis in patients with a first clinical event and at least 2 clinically silent brain magnetic resonance imaging (MRI) lesions. OBJECTIVE: To examine detailed MRI findings from the first 2 years of this trial. DESIGN: Double-blind, placebo-controlled, randomized, parallel-group, multicenter, phase 3 study. SETTING: Ninety-eight centers worldwide. PATIENTS: A total of 404 individuals with a first demyelinating event suggestive of multiple sclerosis. INTERVENTIONS: Patients were randomized to receive interferon beta-1b, 250 microg subcutaneously every other day, or placebo. After 24 months of treatment or on conversion to clinically definite multiple sclerosis, open-label interferon beta 1b treatment was offered. MAIN OUTCOME MEASURES: Reported MRI data from patients completing 2 years of follow-up. RESULTS: Data were analyzed from 248 patients taking interferon beta-1b and 156 taking placebo. Across 2 years the cumulative number of newly active lesions was lower in patients receiving interferon beta-1b vs placebo (median, 2.0 vs 5.0 [reduction of 60%]; P < .001). This corresponded to lower cumulative numbers of new T2 lesions (median, 1.0 vs 3.0 [reduction of 66%]; P < .001) and new gadolinium-enhancing lesions (median, 0.0 vs 1.0; P < .001) in patients receiving interferon beta-1b vs placebo. From screening to month 24, T2 lesion volume decreased and was more pronounced in patients receiving interferon beta-1b (P = .02). CONCLUSIONS: Interferon beta-1b treatment had a robust effect on MRI measures, supporting its value as an early intervention in this patient group. This effect was maintained despite including patients who switched from placebo to interferon beta-1b in the active treatment group. Trial Registration clinicaltrials.gov Identifier: NCT00185211. PMID- 17846270 TI - Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment. AB - BACKGROUND: Memory declines more rapidly with age in apolipoprotein E (APOE) epsilon4 carriers than in APOE epsilon4 noncarriers, and APOE epsilon4 homozygotes' cognitive performances correlate with stressors. These changes could represent presymptomatic disease in some, despite their youth. OBJECTIVE: To show that presymptomatic APOE epsilon4 homozygotes experience greater psychometric decline at a younger age than APOE epsilon4 heterozygotes and noncarriers before the diagnosis of mild cognitive impairment (MCI) and Alzheimer disease (AD). DESIGN: Prospective observational study SETTING: Academic medical center. PARTICIPANTS: A total of 43 APOE epsilon4 homozygotes, 59 APOE epsilon4 heterozygotes, and 112 APOE epsilon4 noncarriers aged 50 to 69 years were cognitively healthy and matched at entry according to age, educational level, and sex. INTERVENTION: Neuropsychological battery given every 2 years. MAIN OUTCOME MEASURES: Predefined test and cognitive domain decline criteria applied to consecutive epochs. RESULTS: Of 214 participants, 48 showed no decline on any test, 126 showed decline on only 1 test in 1 or more domains, and 40 showed decline on 2 or more tests in 1 or more domains. Cognitive domain decline occurred in 4 of 10 APOE epsilon4 homozygotes 60 years and older at entry (40.0%) compared with 5 of 66 APOE epsilon4 heterozygotes and noncarriers (7.6%) (P = .02) and was more predictive of subsequent decline than nondomain decline (17 of 24 [70.8%] vs 29 of 70 [41.4%]; P = .01). Decline on any memory test was predictive of further decline (P < .001), as was memory domain decline (P = .006) in all genetic subgroups. Seven participants developed MCI (in 6) or AD (in 1), of whom 5 were APOE epsilon4 homozygotes (P = .008). Retrospective comparison showed that those who experienced multidomain, memory, and language domain decline had lower spatial and memory scores at entry than those who experienced no decline. CONCLUSIONS: APOE epsilon4 homozygotes in their 60s have higher rates of cognitive domain decline than APOE epsilon4 heterozygotes or noncarriers before the diagnosis of MCI and AD, thus confirming and characterizing the existence of a pre-MCI state in this genetic subset. PMID- 17846271 TI - Superior frontal cortex cholinergic axon density in mild cognitive impairment and early Alzheimer disease. AB - BACKGROUND: Loss of cortical choline acetyltransferase (ChAT) activity contributes to end-stage Alzheimer disease (AD) dementia. In general, ChAT activity levels are stable in the neocortex in mild to moderate AD (mAD) and there is a selective up-regulation in the superior frontal cortex (SFC) in mild cognitive impairment (MCI), indicating a transient, region-specific cholinergic neuroplastic response. OBJECTIVE: To assess whether a proliferation of cholinergic axons underlies increased ChAT activity levels in the SFC in subjects with MCI. DESIGN: Stereologic principles were applied to assess the density of ChAT-immunoreactive fibers and axon varicosities in SFC tissue obtained postmortem from subjects with no cognitive impairment, MCI, and mAD. SUBJECTS: Thirty-six subjects enrolled in the Religious Orders Study, with records of annual clinical evaluation for frontal lobe specific and global cognitive functions. RESULTS: Compared with the group with no cognitive impairment, SFC ChAT-immunoreactive fiber and axon varicosity densities were not altered in the MCI group but were significantly reduced in the group with mAD and correlated with impaired frontal lobe and global cognitive function. CONCLUSIONS: The lack of an increase in cholinergic axonal innervation of the SFC in MCI suggests that structural reorganization of cholinergic profiles is not the mechanism underlying the transient cholinergic plasticity reported in this region. Furthermore, the stability of cholinergic enzyme activity in mAD is likely the result of a biochemical up-regulation of ChAT protein or enzyme activity levels in the SFC, compensating for decreased regional cholinergic fibers and axon varicosities. PMID- 17846272 TI - Whole-body tremulousness: isolated generalized polymyoclonus. AB - BACKGROUND: Acquired generalized repetitive myoclonus may be mistaken for tremor. Distinguishing myoclonus has etiologic and therapeutic implications. OBJECTIVE: To describe isolated generalized polymyoclonus and the outcomes of etiologic evaluations at the time of diagnosis. DESIGN: Computer search of the Mayo Movement Neurophysiology Laboratory database and medical records linkage system. SETTING: Department of Neurology, Mayo Clinic. PATIENTS: Nineteen adults with generalized repetitive myoclonus confirmed using surface electromyography (burst duration <50 milliseconds), and other neurologic features minimal or absent. INTERVENTIONS: Treatment of myoclonus and underlying causes. MAIN OUTCOME MEASURES: Clinical presentation and underlying etiologies. RESULTS: We identified 19 patients with isolated generalized polymyoclonus resembling whole-body tremor. Onset was most often subacute (12 patients), mean symptom duration was 1.8 years, and mean age at onset was 55 years. Referral diagnoses or patient complaints were tremor, tremulousness, or shaking in all but 5 patients. All the patients had repetitive myoclonus of all limbs, impairing gait in 14 patients. Surface electromyography confirmed nonperiodic muscle burst durations of less than 50 milliseconds, typical of myoclonus. Clinical and serologic screening for cancer and autoimmunity revealed metastatic breast cancer in 2 patients (1 positive for ganglionic acetylcholine receptor antibody) and antibody profiles implicating neurologic autoimmunity in 3 patients (CRMP-5 IgG or neuronal voltage-gated potassium channel antibodies). Medications known to occasionally trigger myoclonus (opioids, selective serotonin reuptake inhibitors, and a serotonin norepinephrine reuptake inhibitor) were being taken by 7 patients. Myoclonus resolved after discontinuation of selective serotonin reuptake inhibitor therapy in 1 patient; drug discontinuation was declined and follow-up was inadequate in the other 6. CONCLUSIONS: Isolated whole-body tremulousness should raise the suspicion of generalized polymyoclonus, confirmed using routine surface electromyography. Recognition is important because the differential diagnosis includes autoimmunity and drug-induced myoclonus. PMID- 17846273 TI - A neuropsychological test battery for use in Alzheimer disease clinical trials. AB - OBJECTIVE: To report the psychometric properties of an alternative instrument to the cognitive subscale of the Alzheimer's Disease Assessment Scale, a neuropsychological test battery (NTB) for measuring drug efficacy in Alzheimer disease clinical trials. DESIGN: The NTB was evaluated in a randomized, double blind, placebo-controlled trial of AN1792(QS-21) (synthetic beta-amyloid plus an adjuvant) (300 patients) and isotonic sodium chloride solution (72 patients). The test-retest reliability of the NTB was examined, and the NTB was correlated with other cognitive (cognitive subscale of the Alzheimer's Disease Assessment Scale and Mini-Mental State Examination) and functional (Disability Assessment Scale for Dementia and Clinical Dementia Rating Sum of Boxes) measures. In addition, a factor analysis was performed on NTB components. Finally, the sensitivity of the NTB to change was assessed as a function of Mini-Mental State Examination performance. RESULTS: The NTB had high test-retest reliability at 6 (Pearson product moment correlation [r] = 0.92) and 12 (r = 0.88) months. Internal consistency was high (Cronbach alpha = 0.84). The correlations between the NTB z score and scores on traditional measures of cognition and function were significantly different from 0 (P < .001). A factor analysis yielded "memory" and "executive function" factors. The NTB z score declined linearly over 1 year in patients receiving placebo and, in contrast to the Alzheimer's Disease Assessment Scale cognitive subscale, demonstrated similar declines in patients with high (21 26) and low (15-20) Mini-Mental State Examination scores at baseline. CONCLUSIONS: The NTB exhibits excellent psychometric properties and seems to be a reliable and sensitive measure of cognitive change in patients with mild to moderate Alzheimer disease. The psychometric properties of the NTB suggest that it may have particular utility in evaluating drug efficacy in clinical trials in which patients with mild Alzheimer disease are included. PMID- 17846274 TI - Delayed allergic reaction to natalizumab associated with early formation of neutralizing antibodies. AB - BACKGROUND: Natalizumab is a new therapeutic option for relapsing-remitting multiple sclerosis. As with other antibody therapies, hypersensitivity reactions have been observed. In the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) trial, infusion-related hypersensitivity reactions developed in 4% of patients, usually within 2 hours after starting the infusion. OBJECTIVE: To report a significant, delayed, serum sickness-like, type III systemic allergic reaction to natalizumab. DESIGN: Case report describing clinical follow-up and the serial measurement of antinatalizumab antibodies. PATIENT: A 23-year-old man with relapsing-remitting multiple sclerosis developed a fever, arthralgias, urticarial exanthema, and a swollen lower lip during several days after his second infusion of natalizumab. RESULTS: The patient developed a delayed, serum sickness-like, type III systemic allergic reaction to natalizumab. Five weeks after initiation of this therapy, he tested positive for antinatalizumab antibodies and exhibited persistent antibody titers 8 and 12 weeks later. His symptoms completely resolved with a short course of oral glucocorticosteroids. CONCLUSION: Clinicians and patients should be alert not only to immediate but also to significantly delayed substantial allergic reactions to natalizumab. PMID- 17846275 TI - Congenital myopathy with nemaline rods and cap structures caused by a mutation in the beta-tropomyosin gene (TPM2). AB - OBJECTIVE: To describe the clinical, morphologic, and genetic findings in a family in which one woman had nemaline myopathy, whereas her daughter showed features of cap disease. PATIENTS: A 66-year-old woman and her 35-year-old daughter had congenital, slowly progressive muscle weakness. They had weakness in both proximal and distal muscles and facial diplegia with bilateral ptosis, a long narrow face, a high arched palate, and micrognathia. RESULTS: Muscle biopsy specimens in the mother at age 57 years had shown nemaline myopathy, whereas a biopsy specimen at age 32 years had demonstrated no rods. Muscle biopsy specimens in the daughter at age 26 years had shown features of cap disease and no apparent nemaline rods. A missense mutation, Glu41Lys, in the beta-tropomyosin gene TPM2 was identified in both patients but was absent in their healthy relatives. CONCLUSIONS: The results indicate that mutations in TPM2 may cause nemaline myopathy as well as cap disease with a dominant mode of inheritance. These disorders may thus be phenotypic variants of the same genetic defect. PMID- 17846276 TI - Two novel mitochondrial DNA mutations in muscle tissue of a patient with limb girdle myopathy. AB - BACKGROUND: Defects in the oxidative phosphorylation system can cause a broad spectrum of clinical symptoms ranging from an isolated myopathy to a multisystemic disorder. OBJECTIVE: To study and identify the underlying molecular defect in a patient with limb-girdle myopathy. DESIGN: Biochemical, histochemical, and immunocytochemical analyses were performed in combination with polymerase chain reaction-single-strand conformation polymorphism and restriction fragment length polymorphism-polymerase chain reaction techniques. SETTING: University hospital. PATIENT: A 48-year-old woman with limb-girdle myopathy. MAIN OUTCOME MEASURES: The pathogenic characteristics of the identified nucleotide alterations were defined using single-muscle fiber analysis. RESULTS: A complex III deficiency was detected using blue native-polyacrylamide gel electrophoresis, while immunocytochemical results showed a mosaic staining pattern for complexes I and IV. After molecular analyses, 2 novel heteroplasmic mitochondrial DNA (mtDNA) nucleotide aberrations, m.5888insA and m.14639A>G, were identified in muscle tissue. Single-muscle fiber analyses demonstrated that cytochrome c oxidase deficient fibers, compared with cytochrome c oxidase-positive fibers, harbored statistically significantly higher levels of both mtDNA mutations (P < .001, t test). CONCLUSIONS: These results, together with previously defined canonical criteria determining the pathogenic characteristics of mtDNA mutations, suggest that both nucleotide changes are pathogenic mutations. To our knowledge, this is only the third report of the coexistence of 2 pathogenic mtDNA mutations present in different genes within individual skeletal muscle fibers of a patient. PMID- 17846277 TI - Lamotrigine intoxication provoking status epilepticus in an adult with localization-related epilepsy. AB - BACKGROUND: Various anticonvulsant medications have been associated with paradoxical aggravation of epileptic seizures in therapeutic doses and toxic concentrations. Lamotrigine has been reported to exacerbate seizures and myoclonic seizures in generalized epilepsy in a child with localization-related epilepsy. OBJECTIVE: To describe lamotrigine intoxication paradoxically producing status epilepticus in an adult with localization-related epilepsy. DESIGN: Observational case report. SETTING: Neurology service, inpatient hospitalization, and outpatient follow-up in a neurology clinic. PATIENT: A patient with known localization-related epilepsy who ingested an overdose of lamotrigine tablets in a suicide attempt. INTERVENTION: None. MAIN OUTCOME MEASURE: Observation of the course of the patient's reaction to lamotrigine intoxication, monitoring of lamotrigine levels, and monitoring of ictal and postictal status. RESULTS: The patient developed a prolonged convulsive status epilepticus, which was eventually controlled with benzodiazepines. The patient also developed transient obtundation and severe ataxia, all of which resolved completely within 96 hours. CONCLUSIONS: To our knowledge, in addition to being the first case report to describe convulsive status epilepticus after lamotrigine intoxication, this is the first report of the proconvulsant effect of lamotrigine in a case of localization related epilepsy in an adult. The effects of accidental or suicidal ingestion of lamotrigine tablets seem to be reversible. PMID- 17846278 TI - Value of perfusion computed tomography in stroke mimics. PMID- 17846279 TI - Meningococcal meningitis with brainstem infarction. PMID- 17846280 TI - Humoral immune responses after rabies infection. PMID- 17846281 TI - Biomarkers in dementia. PMID- 17846282 TI - Medication use as a confounding factor in the use of the cerebrospinal fluid tau/beta-amyloid42 ratio. PMID- 17846283 TI - Spinchter symptoms as predictors of long-term disability in multiple sclerosis. PMID- 17846284 TI - Quantitative assessment of the effect of angiotensinogen gene polymorphisms on the risk of coronary heart disease. AB - BACKGROUND: Angiotensinogen, a key protein in the renin-angiotensin system, plays an important role in cardiovascular hemostasis. Many studies have examined the association between polymorphisms in the angiotensinogen gene and risk of coronary heart disease (CHD), but the results have been inconsistent. METHODS AND RESULTS: We performed a meta-analysis of 43 associations studies on 2 angiotensinogen polymorphisms (M235T and T174M) and risk of CHD published before March 2007, including a total of 13,478 CHD cases and 17,024 controls. We also explored potential sources of heterogeneity. In a combined analysis, the summary per-allele odds ratio for CHD of the M235T polymorphism was 1.11 (95% confidence interval, 1.03 to 1.19). However, when the analyses were restricted to 4 larger studies (n >500 cases), the summary per-allele odds ratio was 0.99 (95% confidence interval, 0.94 to 1.04). Our analyses detected a possibility of publication bias with an overestimate of the true association by smaller studies. A meta-analysis of studies on the 174M variant showed no significant overall association with CHD, yielding a per-allele odds ratio of 1.07 (95% confidence interval, 0.93 to 1.22). CONCLUSIONS: This meta-analysis suggested an overall weak association between the M235T polymorphism and CHD risk. However, the association was not observed in several larger studies, suggesting a publication bias. Additional very large-scale studies are warranted to provide conclusive evidence on the effects of the angiotensinogen gene and other genes within the renin-angiotensin system on risk of CHD. PMID- 17846285 TI - Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study. AB - BACKGROUND: Supplementation with vitamin E may antagonize vitamin K in healthy adults, but it is unclear whether intake of vitamin E decreases the risk of venous thromboembolism (VTE). METHODS AND RESULTS: The Women's Health Study randomized 39,876 women > or = 45 years of age to receive 600 IU of natural source vitamin E or placebo on alternate days. Before randomization, 26,779 participants gave blood samples, which were used to determine factor V Leiden, G20210A prothrombin, and 677C>T MTHFR polymorphisms. Documented VTE (including deep vein thrombosis or pulmonary embolism) and unprovoked VTE (no recent surgery, trauma, or cancer diagnosis) were prospectively evaluated, secondary end points of the trial. During a median follow-up period of 10.2 years, VTE occurred in 482 women: 213 in the vitamin E group and 269 in the placebo group, a significant 21% hazard reduction (relative hazard, 0.79; 95% CI, 0.66 to 0.94; P=0.010). For unprovoked VTE, the hazard reduction was 27% (relative hazard, 0.73; 95% CI, 0.57 to 0.94; P=0.016). In subgroup analyses, the 3% of participants who reported VTE before randomization had a 44% hazard reduction (relative hazard, 0.56; 95% CI, 0.31 to 1.00; P=0.048), whereas women without prior VTE had an 18% hazard reduction (relative hazard 0.82; 95% CI, 0.68 to 0.99; P=0.040). Women with either factor V Leiden or the prothrombin mutation had a 49% hazard reduction associated with vitamin E treatment (relative hazard, 0.51; 95% CI, 0.30 to 0.87; P=0.014). CONCLUSIONS: These data suggest that supplementation with vitamin E may reduce the risk of VTE in women, and those with a prior history or genetic predisposition may particularly benefit. PMID- 17846286 TI - Patterns of weight change preceding hospitalization for heart failure. AB - BACKGROUND: Weight gain is used by disease-management programs as a marker of heart failure decompensation, but little information is available to quantify the relationship between weight change in patients with heart failure and the risk for imminent hospitalization. METHODS AND RESULTS: We conducted a nested case control study among patients with heart failure referred to a home monitoring system by managed care organizations. We matched 134 case patients with heart failure hospitalization to 134 control patients without heart failure hospitalization on the basis of age, sex, duration of home monitoring, heart failure severity, and baseline body weight. Compared with control patients, case patients experienced gradual weight gain beginning approximately 30 days before hospitalization; changes in daily weight between case and control patients were statistically significant (P<0.001). Within the week before hospitalization, when weight patterns in case and control patients began to diverge more substantially, mean increases of more than 2 and up to 5 pounds, more than 5 and up to 10 pounds, and more than 10 pounds (relative to time of enrollment in the monitoring system) were associated with matched adjusted odds ratios for heart failure hospitalization of 2.77 (95% confidence interval 1.13 to 6.80), 4.46 (95% confidence interval 1.45 to 13.75), and 7.65 (95% confidence interval 2.22 to 26.39), respectively, compared with mean increases of 2 pounds or less. CONCLUSIONS: Increases in body weight are associated with hospitalization for heart failure and begin at least 1 week before admission. Daily information about patients' body weight identifies a high-risk period during which interventions to avert decompensated heart failure that necessitates hospitalization may be beneficial. PMID- 17846287 TI - High blood pressure trends in children and adolescents in national surveys, 1963 to 2002. AB - BACKGROUND: Secular trend data on hypertension in children and adolescents are scarce and inconsistent. In the face of growing obesity, we sought to assess high blood pressure (HBP) secular trends in children and adolescents enrolled in national surveys and to determine whether the HBP trend reversed its course with the rise in obesity. METHODS AND RESULTS: National survey data obtained from multistage probability sampling of the US noninstitutionalized population from 1963 to 2002 were examined; 8- to 17-year-old non-Hispanic blacks and whites and Mexican Americans were included. HBP ascertainment was based on age-, gender-, and height percentile-specific systolic and diastolic BPs. Weighted analyses were performed to account for the complex design. The BP, pre-HBP, and HBP trends were downward from 1963 to 1988 and upward thereafter. Pre-HBP and HBP increased 2.3% (P=0.0003) and 1% (P=0.17), respectively, between 1988 and 1999. Obesity increase, more so abdominal than general obesity, partially explained the rise in HBP and pre-HBP from 1988 to 1999. BP and HBP reversed their downward trends 10 years after the increase in the prevalence of obesity. Additionally, an ethnic and gender gap appeared in 1988 for pre-HBP and in 1999 for HBP; non-Hispanic blacks and Mexican Americans had a greater prevalence of HBP and pre-HBP than non Hispanic whites, and males had a greater prevalence than females. CONCLUSIONS: HBP and pre-HBP in children and adolescents are on the rise. These new findings have implications for the cardiovascular disease public health burden, particularly the risk of a new cardiovascular disease transition. They reinforce the urgent call for early prevention of obesity and HBP and illustrate racial/ethnic disparities in this age group. PMID- 17846288 TI - Plasminogen activator inhibitor-1 as a predictor of postoperative atrial fibrillation after cardiopulmonary bypass. AB - BACKGROUND: Postoperative atrial fibrillation (AF), leading to significant morbidity and prolongation of hospital stay, complicates 20% to 40% of surgical procedures requiring cardiopulmonary bypass (CPB). This study tests the hypothesis that biomarkers predict the development of postoperative AF. METHODS AND RESULTS: We enrolled 253 adult patients undergoing elective cardiac surgery requiring CPB and who were in sinus rhythm at the time of surgery. Blood samples were obtained for measurement of 21 biomarkers immediately after separation from CPB and administration of protamine. Patients who developed postoperative AF (67 subjects, 26.5%) were significantly older (P<0.001), more likely to have a remote history of AF (P<0.001), and tended to be more likely to have had valve surgery (P=0.082). Plasminogen activator inhibitor-1 (P=0.014), interleukin (IL)-6 (P=0.019), and N-terminal prohormone brain natriuretic peptide (P=0.028) concentrations were significantly higher in the blood of patients who developed postoperative AF. Logistic regression identified age (P<0.001), remote history of AF (P=0.001), and postoperative PAI-1 (P=0.036) as independent predictors of postoperative AF. When preoperative PAI-1 antigen concentrations were included in the model age (P<0.001), remote history of AF (P<0.001) and preoperative PAI-1 (P=0.015) were identified as independent predictors of postoperative AF. The Chi squared Automatic Interaction Detection (CHAID) model indicated that age was the primary determinant for the development of postoperative AF (17% in age < or = 67.3 years versus 49% in age > 67.3 years). Within younger patients (age < or = 67.3 years) without remote history of AF, postoperative PAI-1 antigen concentration next determined risk of AF (13% if PAI-1 < or = 28.5 ng/mL versus 46% if PAI-1 > 28.5 ng/mL). CONCLUSION: An elevated preoperative or postoperative PAI-1 antigen concentration is an independent predictor for development of AF after CPB. Studies are needed to determine whether drugs that reduce PAI-1 concentrations can also reduce the risk of postoperative AF. PMID- 17846289 TI - The MBL2 'LYQA secretor' haplotype is an independent predictor of postoperative myocardial infarction in whites undergoing coronary artery bypass graft surgery. AB - BACKGROUND: Mannose-binding lectin (MBL) is an important component of innate immunity and activator of the lectin complement pathway. Within the MBL2 gene are seven 5' "secretor" haplotypes that code for altered serum MBL levels and complement activation. However, recent evidence suggests that 3' MBL2 haplotypes may also modify MBL function and circulating levels. Because MBL and the lectin complement pathway have been implicated in cardiovascular injury, we investigated whether MBL2 haplotypes are independently associated with an increased risk of postoperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft surgery. METHODS AND RESULTS: Genotyping of 18 polymorphic sites within the MBL2 gene was performed in a prospective, longitudinal multi institutional study of 978 patients undergoing primary coronary artery bypass graft-only surgery with cardiopulmonary bypass between August 2001 and May 2005. After adjustment for multiple comparisons by permutation testing, multivariate, stepwise logistic regression, including a score test, was performed controlling for patient demographics, preoperative risk factors, medications, and intraoperative variables to determine if MBL2 secretor haplotypes are independent predictors of PMI in whites undergoing primary coronary artery bypass graft surgery. Neither the 5' nor 3' MBL2 haplotypes alone were associated with an increased incidence of PMI. However, the incidence of PMI in whites (n=843) expressing the combined MBL2 5' LYQA secretor haplotype (CGTCGG) and 3' haplotype (CGGGT) was significantly higher than in whites not expressing the haplotype (38% versus 10%; P<0.007). Moreover, the combined MBL2 LYQA secretor haplotype was an independent predictor of PMI in whites after primary coronary artery bypass graft surgery after adjustment for other covariates (P<0.02; adjusted OR: 3.97; 95% CI: 1.30 to 12.07). The combined MBL2 LYQA secretor haplotype in whites was also an independent predictor of postoperative CKMB levels exceeding 60 ng/mL (P<0.02; adjusted OR: 4.48; 95% CI: 1.95 to 16.80). Inclusion of the combined MBL2 LYQA secretor haplotype improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.715 versus 0.705). CONCLUSIONS: The combined MBL2 LYQA secretor haplotype is a novel independent predictor of PMI and may aid in preoperative risk stratification of whites undergoing primary coronary artery bypass graft surgery. PMID- 17846290 TI - Transplantation of nanoparticle transfected skeletal myoblasts overexpressing vascular endothelial growth factor-165 for cardiac repair. AB - BACKGROUND: We investigated the feasibility and efficacy of polyethylenimine (PEI) based human vascular endothelial growth factor-165 (hVEGF165) gene transfer into human skeletal myoblasts (HSM) for cell based delivery to the infarcted myocardium. METHODS AND RESULTS: Based on optimized transfection procedure using enhanced green fluorescent protein (pEGFP), HSM were transfected with plasmid hVEGF165 (phVEGF165) carried by PEI (PEI-phVEGF165) nanoparticles. The transfected HSM were characterized for transfection and expression of hVEGF165 in vitro and transplanted into rat heart model of acute myocardial infarction (AMI): group-1=DMEM injection, group-2= HSM transplantation, group-3= PEI-phVEGF165 transfected HSM (PEI-phVEGF165 myoblast) transplantation. A total of 48 rats received cyclosporine injection from 3 days before and until 4 weeks after cell transplantation. Echocardiography was performed to assess the heart function. Animals were sacrificed for molecular and histological studies on the heart tissue at 4 weeks after treatment. Based on optimized transfection conditions, transfected HSM expressed hVEGF165 for 18 days with >90% cell viability in vitro. Apoptotic index was reduced in group-2 and group-3 as compared with group-1. Blood vessel density (x400) by immunostaining for PECAM-1 in group-3 was significantly higher (P=0.043 for both) as compared with group-1 and group-2 at 4 weeks. Regional blood flow (ml/min/g) in the left ventricular anterior wall was higher in group-3 (P=0.043 for both) as compared with group-1 and group-2. Improved ejection fraction was achieved in group-3 (58.44+/-4.92%) as compared with group-1 (P=0.004). CONCLUSION: PEI nanoparticle mediated hVEGF165 gene transfer into HSM is feasible and safe. It may serve as a novel and efficient alternative for angiomyogenesis in cardiac repair. PMID- 17846291 TI - Effects of aprotinin on gene expression and protein synthesis after ischemia and reperfusion in rats. AB - BACKGROUND: Reperfusion injury of ischemic myocardium has been attributed to neutrophil infiltration, inflammatory activation and cardiac necrosis/apoptosis. Serine protease inhibition with aprotinin is cardioprotective, but the mechanism is unknown. METHODS AND RESULTS: We studied aprotinin in a rat model of myocardial ischemia for 20 minutes and reperfusion for 20 minutes, 8 hours or 24 hours. Aprotinin (20,000 IU/kg) given 5 minutes before reperfusion significantly reduced leukocyte accumulation (P<0.01), myocardial injury (determined by CK depletion, P<0.01) and myocyte apoptosis (P<0.05) compared with vehicle treated rats. Differential gene expression analysis showed myocardial ischemia plus reperfusion increased expression of proinflammatory genes like P-selectin, E selectin, intercellular adhesion molecule, tumor necrosis factor-alpha, tumor necrosis factor-alpha receptor, interleukin-6, monocyte chemoattractant protein 1, p53, and Fas (CD59). Aprotinin before reperfusion suppressed expression of these inflammatory genes. Finally, differential protein expression analysis demonstrated increased intercellular adhesion molecule-1, tumor necrosis factor alpha, and p53 after myocardial ischemia plus reperfusion, and this effect was diminished by aprotinin. CONCLUSIONS: We demonstrated myocardial ischemia plus reperfusion induced leukocyte accumulation, inflammation, gene expression, protein expression and finally tissue injury and showed aprotinin limiting reperfusion injury through each of these stages, even after 24 hours of reperfusion. This effect seems partly attributable to suppression of proinflammatory genes and leukocyte accumulation. This work casts further light on the complex signaling of ischemia and reperfusion. PMID- 17846292 TI - Aprotinin does not increase the risk of renal failure in cardiac surgery patients. AB - BACKGROUND: Aprotinin is frequently used in high-risk cardiac surgery patients to decrease bleeding complications and transfusions of packed red blood cells (PRBC). Transfusions of PRBC are known to directly increase the risk of new onset postoperative renal failure (ARF) in cardiac surgery patients. A recent highly publicized report implicated aprotinin as an independent causal factor for postoperative renal failure, but ignored the potential confounding affect of numerical PRBC data on ARF. We sought to investigate that claim with an analysis that included all perioperative risk factors for renal failure, including PRBC transfusion data. METHODS AND RESULTS: Prospectively collected patient data from 12 centers contributing to the Merged Cardiac Registry, an international multicenter cardiac surgery database, operated on between January 2000 and February 2006 were retrospectively analyzed. A previously published risk model for ARF incorporating 12 variables was used to calculate a baseline ARF risk score for each patient in whom those variables were available (n=15,174). After adding transfused PRBC data 11,198 patients remained for risk-adjusted assessment of ARF in relation to aprotinin use. Risk-adjusted multivariable analyses were carried out with, and without, consideration of transfused PRBC. Aprotinin was used in 24.6% (2757/11,198). The overall incidence of ARF was 1.6% (180/11,198) and was higher in the aprotinin subset (2.6%, 72/2757 versus 1.3%, 108/8441; P<0.001). The incidence of ARF directly and significantly increased with increasing transfusions of PRBC (P<0.001). Risk-adjusted analysis without transfused PRBC in the model suggests that aprotinin significantly impacts ARF (P=0.008; OR=1.5). However, further risk adjustment with the addition of the highly significant transfused PRBC variable (P<0.0001; OR=1.23/transfused PRBC) to the model attenuates the purported independent affect of aprotinin (P=0.231) on ARF. CONCLUSIONS: The increase in renal failure seen in patients who were administered aprotinin was directly related to increased number of transfusions in that high-risk patient population. Aprotinin use does not independently increase the risk of renal failure in cardiac surgery patients. PMID- 17846293 TI - Low dose nesiritide and the preservation of renal function in patients with renal dysfunction undergoing cardiopulmonary-bypass surgery: a double-blind placebo controlled pilot study. AB - BACKGROUND: Renal insufficiency is associated with increased morbidity and mortality after cardiopulmonary bypass cardiac surgery. B-type natriuretic peptide is a cardiac hormone that enhances glomerular filtration rate and inhibits aldosterone. Cystatin has been shown to be a better endogenous marker of renal function than creatinine. METHODS AND RESULTS: We performed a double blinded placebo-controlled proof of concept pilot study in patients (n=40) with renal insufficiency preoperatively (defined as an estimated creatinine clearance of <60 mL/min determined by the Cockroft-Gault formula), undergoing cardiopulmonary bypass cardiac surgery. Patients were randomized to placebo (n=20) or i.v. low dose nesiritide (n=20; 0.005 microg/Kg/min) for 24 hours started after the induction of anesthesia and before cardiopulmonary bypass. Patients in the nesiritide group had an increase of plasma B-type natriuretic peptide and its second messenger cGMP with a decrease in plasma cystatin levels at the end of the 24-hour infusion. These changes were not observed in the placebo group. There was a significant activation of aldosterone in the placebo group at the end of the 24-hour infusion, but not in the nesiritide group. At 48 and 72 hours, there was a decrease in estimated creatinine clearance and an increase in plasma cystatin as compared with end of the 24-hour infusion in the placebo group. In contrast, renal function was preserved in the nesiritide group with no significant change in estimated creatinine clearance and a trend for plasma cystatin to increase as compared with end of the 24-hour infusion. CONCLUSION: This proof of concept pilot study supports the conclusion that perioperative administration of low dose nesiritide is biologically active and decreases plasma cystatin in patients with renal insufficiency undergoing cardiopulmonary bypass cardiac surgery. Further studies are warranted to determine whether these physiological observations can be translated into improved clinical outcomes. PMID- 17846294 TI - Multivariable prediction of renal insufficiency developing after cardiac surgery. AB - BACKGROUND: Renal insufficiency after coronary artery bypass graft (CABG) surgery is associated with increased short-term and long-term mortality. We hypothesized that preoperative patient characteristics could be used to predict the patient specific risk of developing postoperative renal insufficiency. METHODS AND RESULTS: Data were prospectively collected on 11,301 patients in northern New England who underwent isolated CABG surgery between 2001 and 2005. Based on National Kidney Foundation definitions, moderate renal insufficiency was defined as a GFR <60 mL/min/1.73 m2 and severe renal insufficiency as a GFR <30. Patients with at least moderate renal insufficiency at baseline were eliminated from the analysis, leaving 8363 patients who became our study cohort. A prediction model was developed to identify variables that best predicted the risk of developing severe renal insufficiency using multiple logistic regression, and the predictive ability of the model quantified using a bootstrap validated C-Index (Area Under ROC) and Hosmer-Lemeshow statistic. Three percent of the patients with normal renal function before CABG surgery developed severe renal insufficiency (229/8363). In a multivariable model the preoperative patient characteristics most strongly associated with postoperative severe renal insufficiency included: age, gender, white blood cell count >12,000, prior CABG, congestive heart failure, peripheral vascular disease, diabetes, hypertension, and preoperative intraaortic balloon pump. The predictive model was significant with chi2 150.8, probability value <0.0001. The model discriminated well, ROC 0.72 (95%CI: 0.68 to 0.75). The model was well calibrated according to the Hosmer-Lemeshow test. CONCLUSIONS: We developed a robust prediction rule to assist clinicians in identifying patients with normal, or near normal, preoperative renal function who are at high risk of developing severe renal insufficiency. Physicians may be able to take steps to limit this adverse outcome and its associated increase in morbidity and mortality. PMID- 17846295 TI - Differential protein kinase C isoform abundance in ascending aortic aneurysms from patients with bicuspid versus tricuspid aortic valves. AB - BACKGROUND: It is recognized that different events contribute to the initiation of ascending thoracic aortic aneurysms (ATAAs) in patients with bicuspid aortic valves (BAV) versus patients with tricuspid aortic valves (TAV), but the molecular signaling pathways driving aneurysm formation remain unclear. Protein kinase C (PKC) is a superfamily of kinases which differentially mediate signaling events that lead to altered gene expression and cellular function, and may regulate downstream mediators of vascular remodeling. The present study tested the hypothesis that ATAA development in patients with BAV versus TAV proceeds by independent signaling pathways involving differential PKC signaling. METHODS AND RESULTS: ATAA samples were collected from BAV (n=57) and TAV (n=55) patients and assessed for 10 different PKC isoforms by immunoblotting. Results were expressed as a percent change in abundance (mean+/-SEM) from a nonaneurysmal control group (100%, n=21). Correlation analysis was performed, and relationships between PKC and matrix metalloproteinase abundance were reported. In the BAV group, classic and novel PKC isoforms (PKC-alpha, betaI, gamma, epsilon, theta) were increased, whereas PKC-eta and atypical PKC-zeta were decreased. In the TAV group, classic and novel isoforms were decreased and atypical PKC-zeta was elevated. Positive correlations between PKC and matrix metalloproteinase abundance were identified. CONCLUSIONS: Differential PKC isoform abundance was observed in ATAA samples from patients with BAV versus TAV, suggesting independent molecular signaling pathways may be operative. Induction of independent transcriptional programs may result and may provide a mechanistic foundation for developing selective diagnostic/therapeutic strategies for patients with ATAAs secondary to BAV or TAV. PMID- 17846296 TI - Acute type B aortic dissection: does aortic arch involvement affect management and outcomes? Insights from the International Registry of Acute Aortic Dissection (IRAD). AB - BACKGROUND: Stanford Type B acute aortic dissection (TB-AAD) spares the ascending aorta and is optimally managed with medical therapy in the absence of complications. However, the treatment of TB-AAD with aortic arch involvement (AAI) remains an unresolved issue. METHODS AND RESULTS: We examined 498 patients with TB-AAD enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2003. Kaplan-Meier mortality curves were constructed and multivariate regression models were performed to identify independent predictors of AAI and to evaluate whether AAI was an independent predictor of follow-up mortality. We found that 371 (74.5%) patients with TB-AAD did not have AAI versus 127 (25.5%) with AAI. Independent predictors of AAI were a history of previous aortic surgery (OR 3.4; 95% CI, 1.6 to 7.6; P=0.002), absence of back pain (OR 1.6; 95% CI, 1.1 to 2.5; P=0.05), and any pulse deficit (1.9; 95% CI, 1.1 to 3.3, P=0.03). Mortality for patients without AAI was 9.4%+/-4.3% and 21.0%+/-6.9% at 1 and 3 years versus 9.2%+/-7.7% and 19.9%+/-11.1% with AAI, respectively (mean follow-up overall, 2.3 years, log rank P=0.82). AAI was not an independent predictor of long-term mortality. CONCLUSIONS: Patients with TB-AAD and aortic arch involvement do not differ with regards to mortality at 3 years. Whether or not AAI involvement impacts other measures of morbidity such as freedom from operation or endovascular intervention deserves further study. PMID- 17846297 TI - The Fontan procedure: contemporary techniques have improved long-term outcomes. AB - BACKGROUND: To determine whether patients undergoing the lateral tunnel and extracardiac conduit modifications of the Fontan procedure have better outcomes than patients undergoing a classical atriopulmonary connection. METHODS AND RESULTS: Between 1980 and 2000, 305 consecutive patients underwent a Fontan procedure at our institution. There were 10 hospital deaths (mortality: 3%) with no death after 1990. Independent risk factors for mortality were preoperative elevated pulmonary artery pressures (P=0.002) and common atrioventricular valve (P=0.04). Fontan was taken down during hospital stay in 7 patients. A mean of 12+/-6 years of follow-up was obtained in the 257 nonforeign Fontan survivors. Completeness of concurrent follow-up was 96%. Twenty-year survival was 84% (95% CI: 79 to 89%). Recent techniques improved late survival. The 15-year survival after atriopulmonary connection was 81% (95% CI: 73% to 87%) versus 94% (95% CI: 79% to 98%) for lateral tunnel (P=0.004). Nine pts required heart transplantation (8 atriopulmonary connection, 1 lateral tunnel). Undergoing a Fontan modification independently predicted decreased occurrence of arrhythmia, and 15-year freedom from SVT was 61% (95% CI: 51% to 70%) for atriopulmonary connection versus 87% (95% CI: 76% to 93%) for lateral tunnel (P=0.02). Freedom from Fontan failure (death, take-down, transplantation, or NYHA class III-IV) was 70% (95% CI: 58% to 79%) at 20 years. After extra-cardiac conduits, no death, SVT, or failure was observed. CONCLUSIONS: The Fontan procedure remains a palliation, but outcomes of patients have improved. Better patient selection minimizes hospital mortality. Patients with lateral tunnel and extracardiac conduit modifications experience less arrhythmia and are likely to have failure of their Fontan circulation postponed. PMID- 17846298 TI - Development of a biological ventricular assist device: preliminary data from a small animal model. AB - BACKGROUND: Engineered heart tissue (EHT) can be generated from cardiomyocytes and extracellular matrix proteins and used to repair local heart muscle defects in vivo. Here, we hypothesized that pouch-like heart muscle constructs can be generated by using a novel EHT-casting technology and applied as heart-embracing cardiac grafts in vivo. METHODS AND RESULTS: Pouch-like EHTs (inner/outer diameter: 10/12 mm) can be generated mainly from neonatal rat heart cells, collagen type I, and serum containing culture medium. They contain a dense network of connexin 43 interconnected cardiomyocytes and an endo-/epicardial surface lining composed of prolylhydroxylase positive cells. Pouch-like EHTs beat spontaneously and show contractile properties of native heart muscle including positive inotropic responses to calcium and isoprenaline. First implantation studies indicate that pouch-like EHTs can be slipped over uninjured adult rat hearts to completely cover the left and right ventricles. Fourteen days after implantation, EHT-grafts stably covered the epicardial surface of the respective hearts. Engrafted EHTs were composed of matrix and differentiated cardiac muscle as well as newly formed vessels which were partly donor-derived. CONCLUSIONS: Pouch-like EHTs can be generated with structural and functional properties of native myocardium. Implantation studies demonstrated their applicability as cardiac muscle grafts, setting the stage for an evaluation of EHT-pouches as biological ventricular assist devices in vivo. PMID- 17846299 TI - Nonlinear power loss during exercise in single-ventricle patients after the Fontan: insights from computational fluid dynamics. AB - BACKGROUND: We previously demonstrated that power loss (PL) through the total cavopulmonary connection (TCPC) in single-ventricle patients undergoing Fontan can be calculated by computational fluid dynamic analysis using 3-dimensional MRI anatomic reconstructions. PL through the TCPC may play a role in single-ventricle physiology and is a function of cardiac output. We hypothesized that PL through the TCPC increases significantly under exercise flow conditions. METHODS AND RESULTS: MRI data of 10 patients with a TCPC were analyzed to obtain 3 dimensional geometry and flow rates through the superior vena cava, inferior vena cava, left pulmonary artery, and right pulmonary artery. Steady computational fluid dynamic simulations were performed at baseline conditions using MRI-derived flows. Simulated exercise conditions of twice (2x) and three times (3x) baseline flow were performed by increasing inferior vena cava flow. PL, head loss, and effective resistance through the TCPC were calculated for each condition. Each condition was repeated at left pulmonary artery/right pulmonary artery ratios of 30/70 and 70/30 to determine the effects of pulmonary flow splits on exercise PL. For each patient, PL increases dramatically in a nonlinear fashion with increasing cardiac output, even when normalized to calculate head loss or resistance. Flow splits had a significant effect on PL at exercise, with most geometries favoring right pulmonary artery flow. CONCLUSIONS: The relationship between cardiac output and PL is nonlinear and highly dependent on TCPC geometry and pulmonary flow splits. This study demonstrates the importance of studying the TCPC under exercise conditions, because baseline conditions may not adequately characterize TCPC efficiency. PMID- 17846300 TI - Pediatric heart transplantation in human leukocyte antigen sensitized patients: evolving management and assessment of intermediate-term outcomes in a high-risk population. AB - BACKGROUND: There is an elevated risk for poor outcomes after heart transplant (HTx) in patients sensitized to human leukocyte antigens including graft dysfunction, acute cellular and antibody-mediated (AMR) rejection, and cardiac allograft vasculopathy. We report our experience with human leukocyte antigens sensitized pediatric HTx recipients. METHODS AND RESULTS: We identified pediatric HTx patients with elevated pre-HTx Panel Reactive Antibody (Class I/II; > 10%), or a positive T- or B-cell crossmatch. Thirteen patients met criteria (5 female, 39%). The median age at HTx was 7 months (3.5 months to 15.5 years). Nine were infants who had prior palliation for congenital heart disease. Four were older patients (median 7.3 years; 4.8 to 15.5 years): 2 had congenital heart disease (Fontan), 2 were re-HTx. B-cell therapies were used in all patients, guided by assessment of CD19+ and CD20+ cells. Immunosuppression included thymoglobulin induction, and tacrolimus, mycophenolate mofetil, and steroids. Daily plasmapheresis +/- intravenous immunoglobulin G was used if there was a positive crossmatch on day 1, with a gradual, biopsy-guided weaning schedule. Rituximab was used when AMR was detected on biopsy: more recently (n=3), used empirically perioperatively. AMR was confirmed in 9 patients within median 0.9 months post HTx. Seven had early acute cellular rejection (> or = ISHLT Grade 2 R) with no hemodynamic compromise or graft dysfunction. There were 4 deaths post-HTx (range, 11 days to 9 months). The median follow-up of 9 survivors was 1.7 years (0.3 to 3.7 years). Of 7 patients > 6 months post-HTx, no AMR or cardiac allograft vasculopathy was observed at a mean of 1.9+1.1 years post-HTx and no cardiac allograft vasculopathy. CONCLUSIONS: Despite aggressive management, acute cellular rejection and AMR occurred frequently early post-HTx. An algorithm of B cell-directed strategies can be effective in managing these patients with reasonable intermediate-term outcomes. PMID- 17846301 TI - Comparison of the profiles of postoperative systemic hemodynamics and oxygen transport in neonates after the hybrid or the Norwood procedure: a pilot study. AB - BACKGROUND: After the Norwood procedure, early postoperative neonatal physiology is characterized by hemodynamic instability and imbalance of oxygen transport that is commonly attributed to surgical myocardial injury and a systemic inflammatory response to cardiopulmonary bypass (CPB). Because the Hybrid procedure (arterial duct stenting and bilateral pulmonary artery banding) avoids CPB, cardioplegic arrest, and circulatory arrest, we hypothesized that the Hybrid procedure is associated with superior postoperative hemodynamics and oxygen transport. METHODS AND RESULTS: Oxygen consumption (VO2) was continuously measured using respiratory mass spectrometry for 72 hours after Hybrid (n=6) and Norwood (n=13) procedures. Arterial, superior vena cava, and pulmonary venous blood gases and pressures were measured at 2- to 4-hour intervals to calculate systemic and pulmonary blood flows (Qs, Qp), and systemic vascular resistance (SVR), total pulmonary vascular resistance including pulmonary arterial band or B T shunt (tPVR), cardiac output (CO), oxygen delivery (DO2), and oxygen extraction ratio (ERO2). Rate-pressure product was calculated as heart rate x systolic arterial pressure. When compared with the Norwood procedure, the early postoperative Hybrid patients had lower CO, higher SVR, and higher Qp:Qs ratios. In addition, the DO2 and VO2 were both lower in the Hybrids with higher ERO2 and lactate levels. This early postoperative pattern reversed after 48 hours. CONCLUSIONS: Although Hybrid procedure avoids CPB and cardioplegic arrest, the early hemodynamic profile is not superior to the Norwood in terms of cardiac output and control of pulmonary blood flow. These data strongly suggest that a "hands off" approach to postoperative care in Hybrid patients may not be appropriate in patients with preoperative diminished myocardial function; and in such patients a Norwood-derived management strategy (afterload reduction and inotropic support) should be considered. PMID- 17846302 TI - Twenty years experience with the gastroepiploic artery graft for CABG. AB - BACKGROUND: To improve the longterm outcome after CABG, several strategies have been used using arterial conduits. Our 20 years experience with the right gastroepiploic artery (GEA) graft was evaluated. METHODS AND RESULTS: In 1352 patients having CABG with the GEA graft, (1092 men, mean 63 years, 99% multivessel disease, and mean EF 0.51), internal thoracic artery, saphenous vein, and radial artery grafts were concomitantly used in 1312 (97%), 783 (58%), and 128 (8%) patients, respectively. The mean number of distal anastomoses was 3.1, and 2.4 coronary arteries were bypassed with arterial grafts. The sites for GEA grafting were 70 anterior descending, 268 circumflex, and 1089 right coronary arteries. The operative mortality was 1.26%. In 1118 follow-up patients (82.6%), 5, 10, and 15 years survival rates were 91.7%, 81.4%, and 71.3%, and the cardiac death-free survival rates were 95.8%, 91.7%, and 88.6%, respectively. The cumulative patency rate of the GEA graft was 97.1% at 1 month, 92.3% at 1 year, 85.5% at 5 years, and 66.5% at 10 years, respectively. In 172 skeletonized GEA grafts with 233 distal anastomoses, the patency rate at immediate, 1, and 4 years after surgery was 97.6%, 92.9%, and 86.4%, respectively. In 124 patients with late (5 to 17 years) restudy, patency rate was 96% (114/119) in the left internal thoracic artery, 87% (108/124) in GEA, and 68% (67/98) in saphenous vein grafts. New stenosis was uncommon in GEA. CONCLUSION: The GEA graft is a safe and effective arterial conduit for CABG. PMID- 17846303 TI - Off-pump techniques disproportionately benefit women and narrow the gender disparity in outcomes after coronary artery bypass surgery. AB - BACKGROUND: Women experience greater morbidity and mortality than men after conventional coronary artery bypass grafting (CABG) on cardiopulmonary bypass (CPB). The objective of this study was to determine whether off-pump CABG (OPCAB) alters this gender-based disparity. METHODS AND RESULTS: Retrospective review of risk factors and clinical outcomes for 11 413 consecutive patients having isolated CABG between January 1, 1997, and May 31, 2005, at a US academic center. Interventions were OPCAB or CABG/CPB, performed at the discretion of 14 faculty surgeons. Main outcome measures included in-hospital death, stroke, myocardial infarction or combined major adverse cardiac events (MACE = death or stroke or myocardial infarction). Odds ratios of adverse events, adjusted for 31 risk factors, were compared between women and men who had OPCAB versus CABG/CPB. Covariates included Propensity Score, Society of Thoracic Surgeons' Predicted Risk, surgeon and body habitus. Female patients (n=3248) and those treated with OPCAB (n=4492) were older, had more comorbidities and higher predicted risk than male patients (n=8165) and those treated with conventional CABG/CPB (n=6921), respectively. Women treated with CABG/CPB had a risk-adjusted odds ratio of 1.60 for death (P=0.01), 1.71 for stroke (P=0.007), 2.26 for myocardial infarction (P=0.008) and 1.71 for MACE (P<0.001) compared with men who had CABG/CPB. In contrast, women treated with OPCAB had outcomes statistically similar to men who had either OPCAB or CABG/CPB. Among women, OPCAB was associated with a significant reduction in death (OR 0.39, P=0.001), stroke (OR 0.43, P=0.002) and MACE (OR 0.43, P<0.001). CONCLUSIONS: OPCAB is associated with fewer major adverse cardiac events and benefits women disproportionately, thereby narrowing the gender disparity in clinical outcomes after CABG. PMID- 17846304 TI - Outcomes of coronary artery bypass grafting versus percutaneous coronary intervention with drug-eluting stents for patients with multivessel coronary artery disease. AB - BACKGROUND: Advances in coronary artery bypass grafting (CABG) surgery and percutaneous coronary intervention (PCI) with drug-eluting stents have dramatically improved results of these procedures. The optimal treatment for patients with multivessel coronary artery disease is uncertain given the lack of prospective, randomized data reflecting current practice. This study represents a "real-world" evaluation of current technology in the treatment of multivessel coronary artery disease. METHODS AND RESULTS: A total of 1680 patients undergoing revascularization for multivessel coronary artery disease were identified. Of these, 1080 patients were treated for 2-vessel disease (196 CABG and 884 PCI) and 600 for 3-vessel disease (505 CABG and 95 PCI). One-year mortality, cerebrovascular events, Q-wave myocardial infarction, target vessel failure, and composite major adverse cardiovascular and cerebrovascular events were compared between the CABG and PCI cohorts. Outcomes were adjusted for baseline covariates and reported as hazard ratios. The unadjusted major adverse cardiovascular and cerebrovascular event rate was reduced with CABG for patients with 2-vessel disease (9.7% CABG versus 21.2% PCI; P<0.001) and 3-vessel disease (10.8% CABG versus 28.4% PCI; P<0.001). Adjusted outcomes showed increased major adverse cardiovascular and cerebrovascular event with PCI for patients with 2-vessel (hazard ratio 2.29; 95% CI 1.39 to 3.76; P=0.01) and 3-vessel disease (hazard ratio 2.90; 95% CI 1.76 to 4.78; P<0.001). Adjusted outcomes for the nondiabetic subpopulation demonstrated equivalent major adverse cardiovascular and cerebrovascular event with PCI for 2-vessel (hazard ratio 1.77; 95% CI 0.96 to 3.25; P=0.07) and 3-vessel disease (hazard ratio 1.70; 95% CI 0.77 to 3.61; P=0.19). CONCLUSIONS: Compared with PCI with drug-eluting stents, CABG resulted in improved major adverse cardiovascular and cerebrovascular event in patients with 2- and 3-vessel coronary artery disease, primarily in those with underlying diabetes. Coronary artery bypass surgery may be the preferred revascularization strategy in diabetic patients with multivessel coronary artery disease. PMID- 17846305 TI - Atherosclerosis secondary prevention performance measures after coronary bypass graft surgery compared with percutaneous catheter intervention and nonintervention patients in the Get With the Guidelines database. AB - BACKGROUND: The American Heart Association Get With the Guidelines-Coronary Artery Disease program facilitates patient and physician compliance with proven atherosclerosis risk reduction strategies with collaborative learning sessions, teaching materials, predischarge online check lists, and web-based performance measure feedback for continuous quality improvement. Patients having coronary artery bypass graft surgery (CABG) may be subject to different care processes, nursing unit pathways, and personnel than patients having percutaneous catheter intervention or neither intervention, which may affect compliance. METHODS AND RESULTS: The Get With the Guidelines-Coronary Artery Disease database was queried to determine whether compliance with secondary prevention performance measures for CABG patients was different from that for nonsurgical patients. A total of 119,106 patients were treated with CABG (14,118), percutaneous catheter intervention (58,702), or neither intervention (46,286). Compliance with medication prescriptions, including aspirin, beta-blockers, angiotensin converting enzyme inhibitors, and lipid-lowering drugs, and smoking cessation counseling for eligible patients was analyzed. Medically appropriate exclusions and contraindications were included in the analysis. After adjusting for 14 clinical variables, CABG patients were less likely to receive most secondary prevention measures relative to percutaneous catheter intervention patients. In contrast, CABG patients were more likely to receive aspirin, beta-blocker, and smoking cessation counseling than neither intervention patients. Composite adherence and defect-free rates were highest for percutaneous catheter intervention patients and lowest for neither intervention patients after adjustment. CONCLUSIONS: There are significant differences in compliance at hospital discharge with secondary prevention performance measures for CABG patients compared with nonsurgical patients. Process of care differences may explain these differences and should be examined further because significant opportunities for improved compliance are evident. CABG patients in particular represent a group for whom secondary prevention has proven benefits, and they may benefit from future quality improvement interventions. PMID- 17846306 TI - Obesity and metabolic syndrome are independent risk factors for atrial fibrillation after coronary artery bypass graft surgery. AB - BACKGROUND: Postoperative atrial fibrillation (POAF) is a highly prevalent complication after cardiac surgery with substantial effects on outcomes. Previous studies have reported that obesity is a risk factor for POAF after cardiac surgery. However, it is unknown whether the metabolic syndrome (MS) also increases the risk of postoperative atrial fibrillation. METHODS AND RESULTS: We retrospectively analyzed the association between obesity and MS and the incidence of new-onset POAF in a total of 5085 patients who underwent isolated coronary artery bypass grafting surgery with no concomitant valvular surgery. Of these patients, 1468 (29%) were obese (body mass index > or = 30 kg/m2) and 2320 (46%) had a MS as defined by the NCEP-ATPIII. POAF occurred in 1374 (27%) of the patients. Obesity was associated (P<0.001) with increased incidence of POAF in the whole cohort as well as in patients > 50 years old but not in patients < or = 50 years old. In these patients, MS was the only metabolic factor to be significantly associated with higher incidence of POAF (12% versus 6%, P=0.01). In > 50-year-old patients, mild (30 < or = body mass index < 35 kg/m2) and moderate-severe (body mass index > or = 35 kg/m2) obesity were independently associated with a 1.4-fold (95% CI: 1.10 to 1.71; P=0.004) and 2.3-fold (95% CI: 1.71 to 3.13; P<0.0001) increase in the risk of POAF, respectively. In < or = 50 year-old patients, MS (relative risk [RR]: 2.36; 95% CI: 1.10 to 5.12; P=0.02) but not obesity was independently associated with POAF. CONCLUSIONS: This study demonstrates that obesity is a powerful risk factor for the occurrence of POAF after isolated coronary artery bypass grafting surgery in patients older than 50 years. However, in the younger population, this association is not observed and MS is the only metabolic risk factor to be independently associated with POAF. PMID- 17846307 TI - Long-term impact of diabetes and its comorbidities in patients undergoing isolated primary coronary artery bypass graft surgery. AB - BACKGROUND: The objective of this study was to identify the impact of diabetes and related comorbidities, namely chronic renal failure, peripheral vascular disease, and low ejection fraction (<35%), on long-term survival of patients undergoing coronary artery bypass graft surgery. METHODS AND RESULTS: A unicenter study was conducted on 9125 survivors of isolated coronary artery bypass graft surgery between 1992 and 2002. There were 6581 nondiabetic patients and 2544 diabetics, including 1809 patients with noninsulin-dependent diabetes mellitus and 735 patients with insulin-dependent diabetes mellitus. Cardiac-specific survival at 5 and 10 years was lower in insulin-dependent diabetes mellitus compared with both nondiabetic mellitus patients and patients with noninsulin dependent diabetes mellitus (P<0.0001). However, freedom from cardiac-related death was similar for patients with noninsulin-dependent diabetes mellitus and nondiabetes mellitus patients up to 6 years (P=0 0.08) after surgery and was significantly lower thereafter (P=0.004). Cardiac-specific survival after coronary artery bypass graft surgery in patients with one or more comorbidities was comparable (P=0.4) for both nondiabetes mellitus patients and patients with noninsulin-dependent diabetes mellitus, but was significantly lower for those requiring insulin therapy (P<0.0001). Noninsulin-dependent diabetes mellitus was not an independent predictor of long-term cardiac death (hazard ratio: 1.09, P=0.41); however, insulin-dependent diabetes mellitus, chronic renal failure, peripheral vascular disease, and low ejection fraction were all independent risk factors for late cardiac death (all P<0.0001). The impact of comorbidities on the long-term risk of cardiac death was similar for the 3 groups. CONCLUSIONS: Noninsulin-dependent diabetes is not an independent predictor of late cardiac death after coronary artery bypass graft surgery, because cardiac-related survival is similar to that of nondiabetic patients for 6 years after surgery. In diabetic and nondiabetic patients, cardiac survival is adversely affected by the need for insulin therapy and/or the presence and number of comorbidities such as chronic renal failure, peripheral vascular disease, and low ejection fraction. PMID- 17846308 TI - Surgical revascularization is associated with improved long-term outcomes compared with percutaneous stenting in most subgroups of patients with multivessel coronary artery disease: results from the Intermountain Heart Registry. AB - BACKGROUND: Coronary artery bypass surgery (CABG) and percutaneous coronary intervention with stenting (PCI-S) are both safe and effective approaches for revascularization in patients with multivessel coronary artery disease. However, conflicting information exists when comparing the efficacy of the two methods. In this study, we examined the outcomes of major adverse cardiovascular events and death for subgroups of typical "real-world" patients undergoing coronary revascularization in the modern era. METHODS AND RESULTS: Patients were included if they were revascularized by CABG or PCI-S, had > or = 5 years of follow-up, and had > or = 2-vessel disease. Patients were followed for an average of 7.0+/ 3.2 years for incidence of death and major adverse cardiovascular events (death, myocardial infarction, or repeat revascularization). Multivariate regression models were used to correct for standard cardiac risk factors including age, sex, hyperlipidemia, diabetes mellitus, family history of coronary artery disease, smoking, hypertension, heart failure, and renal failure. Subgroup analyses were also performed, stratified by age, sex, diabetes, ejection fraction, and history of PCI-S, CABG, or myocardial infarction. A total of 6369 patients (CABG 4581; PCI-S 1788) were included. Age averaged 66+/-10.9 years, 76% were male, and 26% were diabetic. Multivariate risk favored CABG over PCI-S for both death (hazard ratio 0.85; P=0.001) and major adverse cardiovascular events (hazard ratio 0.51; P<0.0001). A similar advantage with CABG was also found in most substrata, including diabetes. CONCLUSIONS: In this large observational study of patients undergoing revascularization for multivessel coronary artery disease, a long-term benefit was found, in relationship to both death and major adverse cardiovascular events, for CABG over PCI-S regardless of diabetic status or other stratifications. PMID- 17846309 TI - A benchmark for evaluating innovative treatment of left main coronary disease. AB - BACKGROUND: Left main trunk stenosis (> or = 50%) has traditionally been treated with coronary artery bypass grafting. Improvements in coronary stents have led some to advocate percutaneous coronary intervention. To provide a benchmark of outcomes against which percutaneous coronary intervention may be compared, we (1) assessed survival and freedom from coronary reintervention after coronary artery bypass grafting in these patients and (2) identified their risk factors. METHODS AND RESULTS: From 1971 to 1998, the first 1000 primary coronary artery bypass grafting patients (n=26,927) were followed every 5 years. Of these, 3803 had left main trunk stenosis > or = 50%. A multivariable, nonproportional hazards, time related analysis was performed to model survival and freedom from coronary reintervention (percutaneous coronary intervention or reoperation) and to identify their risk factors. Survival at 30 days, 1, 5, 10, 15, and 20 years was 97.6%, 93.6%, 83%, 64%, 44%, and 28%, respectively, and freedom from coronary reintervention was 99.7%, 98.9%, 96.6%, 89%, 76%, and 61%, respectively. Worse left ventricular function (P<0.0001), diabetes (P<0.0001), hypertension (P<0.001), peripheral arterial disease (P=0.0002), smoking (P<0.0001), and elevated triglycerides (P=0.01) decreased survival, and younger age (P<0.0001), elevated triglycerides (P=0.005), and incomplete revascularization (P=0.003) increased coronary reintervention. Internal thoracic artery grafting of the left anterior descending improved survival and decreased coronary reintervention. CONCLUSIONS: This study provides a 20-year outcome benchmark for surgical treatment of left main trunk disease. It indicates that simple comparisons of new treatments are inadequate without risk adjustment. Risk factor adjustment should be used when comparing coronary artery bypass grafting with current and future treatment innovations and when selecting the best treatment strategy for individual patients. PMID- 17846310 TI - Bone marrow derived mesenchymal cell mobilization by granulocyte-colony stimulating factor after acute myocardial infarction: results from the Stem Cells in Myocardial Infarction (STEMMI) trial. AB - BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) after myocardial infarction does not affect systolic function when compared with placebo. In contrast, intracoronary infusion of bone marrow cells appears to improve ejection fraction. We aimed to evaluate the G-CSF mobilization of subsets of stem cells. METHODS AND RESULTS: We included 78 patients (62 men; 56+/-8 years) with ST elevation myocardial infarction treated with primary percutaneous intervention <12 hours after symptom onset. Patients were randomized to double-blind G-CSF (10 microg/kg/d) or placebo. Over 7 days, the myocardium was exposed to 25x10(9) G CSF mobilized CD34+ cells, compared with 3x10(9) cells in placebo patients (P<0.001); and to 4.9x10(11) mesenchymal stem cells, compared with 2.0x10(11) in the placebo group (P<0.001). The fraction of CD34+ cells/leukocyte increased during G-CSF treatment (from 0.3+/-0.2 to 1.1+/-0.9 x10(-3), P<0.001 when compared with placebo), whereas the fraction of putative mesenchymal stem cells/leukocyte decreased (from 22+/-17 to 14+/-11 x10(-3), P=0.01 when compared with placebo). An inverse association between number of circulating mesenchymal stem cells and change in ejection fraction was found (regression coefficient 6.8, P=0.004), however none of the mesenchymal cell subtypes analyzed, were independent predictors of systolic recovery. CONCLUSIONS: The dissociated pattern for circulating CD34+ and mesenchymal stem cells could be attributable to reduced mesenchymal stem cell mobilization from the bone marrow by G-CSF, or increased homing of mesenchymal stem cells to the infarcted myocardium. The inverse association between circulating mesenchymal stem cells and systolic recovery may be of clinical importance and should be explored further. PMID- 17846311 TI - Transapical minimally invasive aortic valve implantation: multicenter experience. AB - BACKGROUND: To evaluate initial multicenter results with minimally invasive transapical aortic valve implantation (TAP-AVI) for high risk patients with aortic stenosis. METHODS AND RESULTS: TAP-AVI was performed via a small anterolateral minithoracotomy with or without femoro-femoral extracorporeal circulation (ECC) on the beating heart. A pericardial xenograft fixed within a stainless steel, balloon expandable stent (Edwards SAPIEN THV, Edwards Lifesciences) was used. Fifty-nine consecutive patients (81+/-6 years, 44 female) were operated on from 02/06 until 10/06 at 4 centers using fluoroscopic and echocardiographic visualization. Average EuroSCORE predicted risk for mortality was 27+/-14%. TAP valve positioning was performed successfully in 53 patients, 4 required early conversion to sternotomy. Implantation (23-mm valves in 19 and 26 mm valves in 40 patients) was performed on the beating heart during brief periods of rapid ventricular pacing. Thirty-one patients were operated on without cardiopulmonary bypass. Neither coronary artery obstruction nor migration of the prosthesis was observed, and all valves had good hemodynamic function. Echocardiography revealed minor paravalvular leakage in 26 patients (trace in 11, mild in 12, and severe in 3). Eight patients died in-hospital (13.6%) without any valve dysfunction. Actuarial survival was 75.7+/-5.9% at a follow-up interval of 110+/-77 days (range 1 to 255 days). CONCLUSIONS: TAP-AVI can be performed safely with good early results in high risk patients. Long-term valve performance as well as broader based applications of this promising approach will need to be studied. PMID- 17846312 TI - Percutaneous mitral valvuloplasty versus surgical treatment in mitral stenosis with severe tricuspid regurgitation. AB - BACKGROUND: The persistence of significant tricuspid regurgitation (TR) after percutaneous mitral valvuloplasty (PMV) is known to be an independent predictor of adverse outcome in mitral stenosis (MS). However, it remains unclear whether mitral valve (MV) surgery combined with surgical correction of TR is the better treatment option than PMV in patients with severe MS and severe functional TR. METHODS AND RESULTS: We included a total of 92 consecutive patients (18 men, age 49+/-13 years) with severe MS and severe functional TR, who were potential candidates for PMV from 1997 to 2005, and the exclusion criteria were defined as the presence of left atrial thrombi, mitral regurgitation > or = grade 3, echo score > 10, and left ventricular ejection fraction (EF) < 35%. PMV was performed on 48 patients (PMV group), and MV surgery combined with tricuspid valve (TV) repair was performed on 44 patients (TVP group). The clinical events were defined as death, repeat surgical or percutaneous intervention, and readmission because of heart failure. There were no significant differences between the 2 groups in terms of gender, baseline EF, and baseline severity of pulmonary hypertension, but patients in the TVP group were older and had a higher echo score and a higher incidence of atrial fibrillation than those in the PMV group. During follow-up of 57+/-35 months, 2 deaths occurred in the TVP group, and there were 2 deaths, 7 cases of heart failure requiring surgical intervention in the PMV group. The difference of event rates between the 2 groups showed borderline significance (P=0.05), but no difference in mortality was observed. The estimated actuarial 7 year event-free survival rate was 77+/-8% in the PMV group and 95+/-3% in the TVP group. Severe TR was improved to mild or absent TR in 43 (98%) patients in the TVP group, and this was significantly higher than in the PMV group (22/48, 46%; P<0.001). In the TVP group, the right ventricle (RV) size was significantly decreased in 18 (90%) patients among 20 patients with preoperative significant RV enlargement. On stepwise multivariate logistic regression analysis, TVP group and baseline sinus rhythm were independent predictors for improvement of TR (P<0.001). CONCLUSIONS: TV repair combined with MV surgery was related to better clinical outcomes than PMV alone, and we recommend that this surgical option should be considered preferentially in severe MS with severe functional TR, especially if atrial fibrillation or enlarged RV is associated. PMID- 17846313 TI - Autograft regurgitation and aortic root dimensions after the Ross procedure: the German Ross Registry experience. AB - BACKGROUND: Autograft regurgitation and root dilatation after the Ross procedure is of major concern. We reviewed data from the German Ross Registry to document the development of autograft regurgitation and root dilatation with time and also to compare 2 different techniques of autograft implantation. METHODS AND RESULTS: Between 1990 and 2006 1014 patients (786 men, 228 women; mean age 41.2+/-15.3 years) underwent the Ross procedure using 2 different implantation techniques (subcoronary, n=521; root replacement, n=493). Clinical and serial echocardiographic follow up was performed preoperatively and thereafter annually (mean follow up 4.41+/-3.11 years, median 3.93 years, range 0 to 16.04 years; 5012 patient-years). For statistical analysis of serial echocardiograms, a hierarchical multilevel modeling technique was applied. Eight early and 28 late deaths were observed. Pulmonary autograft reoperations were required in 35 patients. Initial autograft regurgitation grade was 0.49 (root replacement 0.73, subcoronary 0.38) with an annual increase of grade 0.034 (root replacement 0.0259, subcoronary 0.0231). Annulus and sinus dimensions did not exhibit an essential increase over time in both techniques, whereas sinotubular junction diameter increased essentially by 0.5 mm per year in patients with root replacement. Patients with the subcoronary implantation technique showed nearly unchanged dimensions. Bicuspid aortic valve morphology did not have any consistent impact on root dimensions with time irrespective of the performed surgical technique. CONCLUSIONS: The present Ross series from the German Ross Registry showed favorable clinical and hemodynamic results. Development of autograft regurgitation for both techniques was small and the annual progression thereof is currently not substantial. Use of the subcoronary technique and aortic root interventions with stabilizing measures in root replacement patients seem to prevent autograft regurgitation and dilatation of the aortic root within the timeframe studied. PMID- 17846314 TI - Persistent reduction of ischemic mitral regurgitation by papillary muscle repositioning: structural stabilization of the papillary muscle-ventricular wall complex. AB - BACKGROUND: Recurrent ischemic mitral regurgitation (IMR) is frequent despite initial reduction by annuloplasty because continued LV remodeling increases tethering to the infarcted papillary muscle (PM). We have previously shown that PM repositioning by an external patch device can acutely reduce IMR. In this study, we tested the hypothesis that IMR reduction persists despite possible continued LV remodeling. METHODS AND RESULTS: In 7 sheep, we used a chronic ischemic posterior infarct model that produces LV dilatation and MR over 10 weeks. An epicardial patch device was adjusted under echo guidance to reduce MR, with follow-up over a further 8 weeks and evaluation by 3D echo and sonomicrometry. In all 7 sheep, moderate IMR resolved with acute patch application and PM repositioning (6.5+/-1.8 mm to 0.6+/-1.3 mm proximal jet width, P<0.001) without decrease in LVEF (43+/-3% to 44+/-8%). Eight weeks after PM repositioning, MR was not significantly greater (0.6+/-1.3 mm versus 1.0+/-1.0 mm, P=NS) despite an increase in LV volumes in 3 animals (2 had increases of 50+/ 15%). On average, LV volumes did not change significantly (ESV: 46+/-8 mL versus 49+/-15 mL; P=NS and EDV: 85+/-16 mL versus 89+/-30 mL; P=NS). LVEF was unchanged from acute to chronic patch (44+/-8% versus 43+/-8%). Contractility as end systolic elastance did not decrease from the chronic MI to the acute and chronic patch stages, nor were there any significant changes in dP/dt, LV stiffness constant, or time constant of LV relaxation (Tau). CONCLUSION: PM repositioning is persistently effective in reducing moderate chronic IMR, even when LV volume increases. This may reflect structural stabilization by an external patch device of the papillary muscle-LV wall complex that controls mitral valve tethering. PMID- 17846315 TI - Functional anatomy of aortic regurgitation: accuracy, prediction of surgical repairability, and outcome implications of transesophageal echocardiography. AB - BACKGROUND: For patients with aortic regurgitation (AR), aortic valve sparing or repair surgery is an attractive alternative to valve replacement. In this setting, accurate preoperative delineation of aortic valve pathology and potential repairability is of paramount importance. The aim of the present study was to assess the diagnostic value of preoperative transesophageal echocardiography (TEE) in defining the mechanisms of AR, as identified by surgical inspection, and in predicting repairability, by using the final surgical approach as reference. METHODS AND RESULTS: One hundred and sixty-three consecutive patients (117 males, mean age: 58+/-14 years) undergoing AR surgery were included. Mechanisms of AR were categorized by TEE and surgical inspection as follows: type 1, aortic dilatation; type 2, cusp prolapse; and type 3, restrictive cusp motion or endocarditis. At surgery, mechanisms of AR were type 1 in 41 patients, type 2 in 62, and type 3 in 60. Agreement between TEE and surgical inspection was 93% (kappa=0.90). Valve sparing or repair was performed in 125 patients and valve replacement in 38 patients. TEE correctly predicted the final surgical approach in 108/125 (86%) patients undergoing repair and in 35/38 (93%) patients undergoing replacement. The gross anatomic classification of AR lesions by TEE was determinant of valve repairability and postoperative outcome (4-year freedom from > grade 2 AR, reoperation, or death, P=0.04). CONCLUSIONS: TEE provides a highly accurate anatomic assessment of all types of AR lesions. In addition, the functional anatomy of AR defined by TEE is strongly and independently predictive of valve repairability and postoperative outcome. PMID- 17846316 TI - Endoscopic mitral and tricuspid valve surgery after previous cardiac surgery. AB - BACKGROUND: The purpose of this study was to evaluate the feasibility and effectiveness of a right video-assisted approach for atrioventricular valve disease after previous cardiac surgery. METHODS AND RESULTS: Between December 1st 1997 and May 1st 2006, 80 adults (mean age 65+/-12 years; 56% female) underwent reoperative surgery using a video-assisted approach without rib spreading. Previous cardiac operations included mitral valve (39%), CABG (29%), congenital (10%), and other (23%). For 25% of patients, this was at least their third cardiac operation. Mean time to redo surgery was 15+/-12 years. Femoral vessel cannulation and endoaortic clamping were routinely used. Mean preoperative Euroscore was 9.0+/-2.7 (5 to 20) and predicted mortality was 16.0+/-14.2% (4 to 86). Median preoperative NYHA class was II and mean follow-up was 25+/-22 months. Lung adhesions necessitated sternotomy in 4 cases and cannulation problems in another patient. Total operative mortality was 3.8% (n=3), O/E for mortality being 0.24. Procedures were mitral valve repair (45%; n=36), replacement (50%; n=40) and tricuspid valve replacement (5%; n=4). Additional procedures were performed in 44% (n=35). Mean aortic crossclamp and procedure time were 92+/-37 and 267+/-64 minutes. Mean postoperative blood loss was 815+/-1083 mL. Postoperative morbidity included 2 strokes (2.5%). Mean hospital stay was 10.7+/ 6.7 days. Survival at 1 and 4 years was 93.6+/-2.8% and 85.6+/-6.4%. There was 1 late reoperation at 5 years. Median NYHA class at follow-up was II. When comparing, all but 1 patient (98.8%) preferred their minimally invasive approach when considering perioperative pain, postoperative rehabilitation, and final esthetic result. CONCLUSIONS: Video-assisted minimal access correction of atrioventricular valve disease after previous cardiac surgery is not only feasible but had lower than predicted mortality and strong patient satisfaction. It should therefore be used more frequently in today's practice. PMID- 17846317 TI - Effect of chronotropy and inotropy on stitch tension in the edge-to-edge mitral repair. AB - BACKGROUND: Our prior studies suggest that mitral annular septal-lateral (SL) diameter is the chief determinant of "Alfieri stitch" tension, but hemodynamic parameters may also play a role. We approximated the central edge of the mitral leaflets with a miniature force transducer to measure tension (T) at the leaflet approximation point during inotropic and chronotropic stimulation. METHODS AND RESULTS: Eight sheep were studied under open-chest conditions immediately after surgical placement of a miniature force transducer to approximate the leaflets and implantation of radiopaque markers on the LV and mitral annulus (MA). Chronotropic stimulation was induced with atrial pacing at 130 minutes(-1) (n=5) whereas inotropic state was increased with i.v. CaCl2 bolus (n=8). Hemodynamic data, stitch tension, and 3-D marker coordinates were obtained throughout the cardiac cycle before and during each intervention. Peak stitch tension (T(MAX)) under all conditions was observed in diastole and temporally correlated with peak annular SL (SL(MAX)) size. Atrial pacing did not change peak transducer tension or annular size. Calcium infusion also did not alter peak transducer tension (0.29+/-0.11 versus 0.32+/-0.10 N; P=NS) and only slightly reduced SL dimension (29.9+/-3.3 versus 29.3+/-3.5 mm; P<0.05). CONCLUSION: Isolated increase in heart rate or inotropic state did not alter peak stitch tension whereas enhanced contractile state decreased SL diameter minimally. These data, combined with those from our previous study, suggest that geometric (SL diameter) rather than hemodynamic parameters are the main determinants of "Alfieri stitch" tension. This implies that any interventional or surgical edge-to-edge repair performed without concomitant annular reduction to limit the SL dimension could expose the leaflet junction to forces which could limit repair durability. PMID- 17846318 TI - A novel role of the sympatho-adrenergic system in regulating valve calcification. AB - BACKGROUND: Aortic valve calcification is a progressive process resembling ossification. Recent evidence indicates that the sympathetic nervous system plays an important role in regulating bone deposition and resorption through the beta2 adrenergic receptors (beta2-ARs). The aim of this study is to determine the level and pattern of expression of beta2-ARs in human valve interstitial cells (ICs) and assess their influence on differentiation of the cells into an osteoblast like phenotype. METHODS AND RESULTS: Immunohistochemical analysis demonstrated a high expression of beta2-ARs, beta1-ARs, beta3-AR,s and receptor activator of nuclear factor-kappaB (RANK) in calcified aortic valves. The expression of beta2 ARs and beta1-ARs mRNA was assessed by real-time TaqMan PCR in cultures of human aortic valve ICs. Human valve ICs treated with the selective beta2-AR agonist, salmeterol, in the presence of osteogenic medium showed a significant 5-fold decrease in the alkaline phosphatase (ALP) activity in comparison to cells treated with osteogenic medium only (P<0.05). Immunocytochemical staining of the valve ICs showed a concomitant reduction in osteocalcin expression. In addition, other beta2-AR agonists caused a reduction in the protein expression of bone markers including ALP, Cbfa-1, and periostin. Human valve ICs treated with norepinephrine, in the presence of osteogenic medium, did not show a significant reduction in the ALP activity. CONCLUSIONS: These findings suggest an important role of the beta2-ARs in regulating valve calcification and may identify potential therapeutic targets. PMID- 17846319 TI - Early repair of moderate ischemic mitral regurgitation reverses left ventricular remodeling: a functional and molecular study. AB - BACKGROUND: Mitral regurgitation (MR) doubles postmyocardial infarction (MI) mortality. We have shown that moderate MR augments remodeling in an apical MI model (no intrinsic MR) with independent left ventricle-to-left atrial MR-type flow. We hypothesized that repairing moderate MR 1 month after MI reverses this remodeling. METHODS AND RESULTS: Anteroapical MIs were created in 18 sheep, and a left ventricle-to-left atrial shunt implanted in 12 (regurgitant fraction, 30%). Six sheep had the shunt closed at 1 month (repair group). Sheep were compared at baseline, and at 1 and 3 months. Sheep in the MI+MR (unrepaired) and repaired groups remodeled during the first month (120% increased left ventricular end systolic volume [ESV; P<0.01]), but shunt closure reversed remodeling at 3 months, with end-diastolic volume (EDV) and ESV 135% and 128% of baseline versus 220% and 280% without repair (P<0.001). At 3 months, dP/dt and preload recruitable stroke work were relatively maintained in the repaired and MI-only groups versus nearly 50% decreases without repair. Prohypertrophic gp130 and antiapoptotic pAkt increased followed by exhaustion below baseline without repair, but remained elevated at 3 months with repair or MI only. With repair, matrix metalloproteinase-2 decreased to < or = 50% that without repair in remote and border zones at 3 months, and the matrix metalloproteinase inhibitor TIMP-4 increased dramatically. CONCLUSIONS: Early repair of moderate MR in the setting of apical MI substantially reverses the otherwise progressive remodeling process, with reduced left ventricular volumes, relatively maintained contractility, persistently activated intracellular signals promoting hypertrophy and opposing apoptosis, and reduced matrix proteolytic activity. These findings are of interest for the current controversy regarding potential benefits of repair of MR after MI. PMID- 17846320 TI - Very long-term survival implications of heart valve replacement with tissue versus mechanical prostheses in adults <60 years of age. AB - BACKGROUND: Several centers favor replacing a diseased native heart valve with a tissue rather than a mechanical prosthesis, even in younger adult patients. However, long-term data supporting this approach are lacking. We examined the survival implications of selecting a tissue versus a mechanical prosthesis at initial left-heart valve replacement in a cohort of adults <60 years of age who were followed for over 20 years. METHODS AND RESULTS: Comorbid and procedural data were available from 6554 patients who underwent valve replacement at our institution over the last 35 years. Of these, 1512 patients contributed follow-up data beyond 20 years, of whom 567 were adults <60 years of age at first left heart valve operation (mean survivor follow-up, 24.0+/-3.1 years). Late outcomes were examined with Cox regression. Valve reoperation, often for prostheses that are no longer commercially available, occurred in 89% and 84% of patients by 20 years after tissue aortic and mitral valve replacement, respectively, and was associated with a mortality of 4.3%. There was no survival difference between patients implanted with a tissue versus a mechanical prosthesis at initial aortic valve replacement (hazard ratio 0.95; 95% CI: 0.7, 1.3; P=0.7). For mitral valve replacement patients, long-term survival was poorer than after aortic valve replacement (hazard ratio 1.4; 95% CI: 1.1, 1.8; P=0.003), but again no detrimental effect was associated with use of a tissue versus a mechanical prosthesis (hazard ratio 0.9; 95% CI 0.5, 1.4; P=0.5). CONCLUSIONS: In our experience, selecting a tissue prosthesis at initial operation in younger adults does not negatively impact survival into the third decade of follow-up, despite the risk of reoperation. PMID- 17846321 TI - Composite aortic valve graft replacement: mortality outcomes in a national registry. AB - BACKGROUND: Composite aortic valve and root replacement (CVG) is a complex surgical procedure, but excellent center-specific outcomes are reported. We sought to report outcomes in a national cohort. METHODS AND RESULTS: The United Kingdom Heart Valve Registry was interrogated for 1962 first-time CVG (and 37,102 aortic valve replacements [AVR] as a reference group) procedures from 1986 to 2004. We analyzed 30-day mortality, long-term survival (97.2% complete follow up), and examined available risk factors for mortality using univariate and multivariate logistic regression analysis and causes of death. CVG patients were younger, received larger valve sizes and were more likely to be emergent than AVR patients. Overall 30-day mortality was 10.7% (CVG) and 3.6% (AVR). For CVG, multivariate analysis identified advanced age (> 70 years), concomitant coronary artery surgery, impaired left ventricular function, urgent or emergency status, prosthetic valve size < or = 23 mm and hospital activity volume < or = 8 procedures per annum as significant factors for 30-day mortality. Kaplan-Meier, 1 year, 5-year, 10-year and 20-year survival were 85.2%, 77.1%, 70% and 59.3%, respectively. The conditional (post-30-day) survival was similar to the AVR cohort. CONCLUSIONS: These Registry data provide a unique national insight into CVG outcomes. After a higher initial mortality risk, CVG has equivalent conditional longer-term survival to AVR. PMID- 17846322 TI - Limited long-term durability of the Cryolife O'Brien stentless porcine xenograft valve. AB - BACKGROUND: Despite the fact that early and midterm hemodynamic and clinical results of the Cryolife O'Brien (CLOB) stentless valve have been reported to be favorable, the long-term durability and clinical results of this valve are largely unknown. Accordingly, we analyzed 10-year outcomes after aortic valve replacement with this valve. METHODS AND RESULTS: From January 1994 to September 2004, 185 patients (67, 73, and 75 years, 25th, 50th, and 75th quartiles, respectively; 38% older than 75 years; 56% females) underwent aortic valve replacement with the CLOB valve. Sixty-eight percent of patients were in NYHA class 3 to 4. Standard EuroSCORE was 7.1+/-2.7. Pure aortic stenosis accounted for 42% (n=79), and pure insufficiency for 12% of cases (n=22). Concomitant surgery: 28% coronary artery bypass (n=51), 11% mitral valve replacement/annuloplasty (n=21), and 2% ascending aorta replacement (n=3). Sixty one percent of patients received a 23-mm valve or smaller size. Follow-up was 100% completed, and cumulative follow-up was 65 months/patient. The 30-day mortality was 5.4% (none were valve related). Actuarial survival at 5 and 10 years were 68% and 40%, respectively. Actuarial freedom from structural valve deterioration was 91% at 5 years and dropped to 44% at 10 years. Actuarial freedom from reoperation was 94% at 5 years and declined to 57% at 10 years. CONCLUSIONS: In a population with a high prevalence of elderly females with small aortic root, the CLOB valve demonstrated satisfactory clinical results till 8 years. Afterward, a significant increase in hazard for structural valve deterioration and reoperation occurred in late follow-up. PMID- 17846323 TI - Functional, cellular, and molecular characterization of the angiogenic response to chronic myocardial ischemia in diabetes. AB - BACKGROUND: Ischemic heart disease is the most common cause of mortality in diabetic patients. Although therapeutic angiogenesis is an attractive option for these patients, they appear to have reduced collateral formation in response to myocardial ischemia. The aims of this study were to establish a large animal model of diabetes and chronic myocardial ischemia, evaluate the effects of diabetes on the angiogenic response, and elucidate the molecular pathways involved. METHODS AND RESULTS: Diabetes was induced in male Yucatan miniswine using a pancreatic beta-cell specific toxin, alloxan (150 mg/kg; n=8). Age matched swine served as controls (n=8). Eight weeks after induction, chronic ischemia was induced by ameroid constrictor placement around the circumflex coronary artery. Myocardial perfusion and function were assessed at 3 and 7 weeks after ameroid placement using isotope-labeled microspheres. Endothelial cell density and myocardial expression of angiogenic mediators was evaluated. Diabetic animals exhibited significant endothelial dysfunction. Collateral dependent perfusion and LV function were significantly impaired in diabetic animals. Diabetic animals also demonstrated reduced endothelial cell density (173+/-14 versus 234+/-23 cells/hpf, P=0.03). Expression of VEGF, Ang-1, and Tie-2 was reduced, whereas antiangiogenic proteins, angiostatin (4.4+/-0.9-fold increase, P<0.001), and endostatin (2.9+/-0.4-fold increase, P=0.03) were significantly elevated in the diabetic myocardium. CONCLUSIONS: Diabetes results in a profound impairment in the myocardial angiogenic response to chronic ischemia. Pro- and antiangiogenic mediators identified in this study offer novel targets for the modulation of the angiogenic response in diabetes. PMID- 17846324 TI - Iron-oxide labeling and outcome of transplanted mesenchymal stem cells in the infarcted myocardium. AB - BACKGROUND: Cell labeling with superparamagnetic iron oxide (SPIO) nanoparticles enables noninvasive MRI and tracking of transplanted stem cells. We sought to determine whether mesenchymal stem cell (MSC) outcome is affected by SPIO labeling in a rat model of myocardial infarction. METHODS AND RESULTS: Rat MSCs were labeled with SPIO (ferumoxides; Endorem; Guerbet, Villepinte, France). By trypan-blue exclusion assay, almost 100% of the cells remained viable after labeling. Seven days after MI, rats were randomized to injections of 2x10(6) SPIO labeled MSCs, 2x10(6) unlabeled MSCs, or saline. Labeled cells were visualized in the infarcted myocardium as large black spots by serial MRI studies throughout the 4-week follow-up. The presence of labeled cells was confirmed by iron staining and real-time polymerase chain reaction on postmortem specimens. At 4 weeks after transplantation, the site of cell injection was infiltrated by inflammatory cells. Costaining for iron and ED1 (resident macrophage marker) showed that the iron-positive cells were cardiac macrophages. By real-time polymerase chain reaction, the Y-chromosome-specific SRY DNA of MSCs from male donors was not detected in infarcted hearts of female recipients. Serial echocardiography studies at baseline and 4 weeks after cell transplantation showed that both unlabeled and labeled MSCs attenuated progressive left ventricular dilatation and dysfunction compared with controls. CONCLUSIONS: At 4 weeks after transplantation of SPIO-labeled MSCs, the transplanted cells are not present in the scar and the enhanced MRI signals arise from cardiac macrophages that engulfed the SPIO nanoparticles. However, both labeled and unlabeled cells attenuate left ventricular dilatation and dysfunction after myocardial infarction. PMID- 17846325 TI - Differentiation, survival, and function of embryonic stem cell derived endothelial cells for ischemic heart disease. AB - BACKGROUND: Embryonic stem (ES) cells are distinguished by their capacity for self-renewal and pluripotency. Here we characterize the differentiation of ES cell-derived endothelial cells (ESC-ECs), use molecular imaging techniques to examine their survival in vivo, and determine the therapeutic efficacy of ESC-ECs for restoration of cardiac function after ischemic injury. METHODS AND RESULTS: Murine ES cells were transfected with a construct composed of a vascular endothelial cadherin promoter driving enhanced green fluorescence protein (pVE cadherin-eGFP). Differentiation of ES cells to ECs was detected by FACS analysis using Flk-1 (early EC marker at day 4) and VE-cadherin (late EC marker at day 8). After isolation, these ESC-ECs express endothelial cell markers similar to adult mouse lung endothelial cells, form vascular-like channels, and incorporate DiI labeled acetylated low-density lipoprotein (DiI-Ac-LDL). For in vivo imaging, ES cells were transduced with an ubiquitin promoter driving firefly luciferase and monomeric red fluorescence protein (pUb-Fluc-mRFP). A robust correlation exists between Fluc signals and cell numbers by ex vivo imaging analysis (R2=0.98) and by in vitro enzyme assay (R2=0.94). Afterward, 5x10(5) ESC-ECs or PBS (as control) was injected into the hearts of mice undergoing LAD ligation (n=15 per group). Bioluminescence imaging showed longitudinal survival of transplanted ESC ECs for approximately 8 weeks. Echocardiogram demonstrated significant functional improvement in the ESC-EC group compared with control (P=0.04). Finally, postmortem analysis confirmed increased presence of small capillaries and venules in the infarcted zones by CD31 staining. CONCLUSIONS: This is the first study to track the fate and function of transplanted ESC-ECs in the heart. With further validation, these ESC-ECs could become a valuable source of cell therapy for induction of angiogenesis in the treatment of myocardial ischemia. PMID- 17846326 TI - Protein precoating of elastomeric tissue-engineering scaffolds increased cellularity, enhanced extracellular matrix protein production, and differentially regulated the phenotypes of circulating endothelial progenitor cells. AB - BACKGROUND: Optimal cell sources and scaffold-cell interactions remain unanswered questions for tissue engineering of heart valves. We assessed the effect of different protein precoatings on a single scaffold type (elastomeric poly (glycerol sebacate)) with a single cell source (endothelial progenitor cells). METHODS AND RESULTS: Elastomeric poly (glycerol sebacate) scaffolds were precoated with laminin, fibronectin, fibrin, collagen types I/III, or elastin. Characterized ovine peripheral blood endothelial progenitor cells were seeded onto scaffolds for 3 days followed by 14 days incubation. Endothelial progenitor cells were CD31+, vWF+, and alpha-SMA- before seeding confirmed by immunohistochemistry and immunoblotting. Both precoated and uncoated scaffolds demonstrated surface expression of CD31+ and vWF+, alpha-SMA+ cells and were found in the "interstitium" of the scaffold. Protein precoating of elastomeric poly (glycerol sebacate) scaffolds revealed significantly increased cellularity and altered the phenotypes of endothelial progenitor cells, which resulted in changes in cellular behavior and extracellular matrix production. Moreover, mechanical flexure testing demonstrated decreased effective stiffness of the seeded scaffolds compared with unseeded controls. CONCLUSIONS: Scaffold precoating with extracellular matrix proteins can allow more precise "engineering" of cellular behavior in the development of tissue engineering of heart valves constructs by altering extracellular matrix production and cell phenotype. PMID- 17846327 TI - Prenatally fabricated autologous human living heart valves based on amniotic fluid derived progenitor cells as single cell source. AB - BACKGROUND: A novel concept providing prenatally tissue engineered human autologous heart valves based on routinely obtained fetal amniotic fluid progenitors as single cell source is introduced. METHODS AND RESULTS: Fetal human amniotic progenitors were isolated from routinely sampled amniotic fluid and sorted using CD133 magnetic beads. After expansion and differentiation, cell phenotypes of CD133- and CD133+ cells were analyzed by immunohistochemistry and flowcytometry. After characterization, CD133- derived cells were seeded onto heart valve leaflet scaffolds (n=18) fabricated from rapidly biodegradable polymers, conditioned in a pulse duplicator system, and subsequently coated with CD133+ derived cells. After in vitro maturation, opening and closing behavior of leaflets was investigated. Neo-tissues were analyzed by histology, immunohistochemistry, and scanning electron microscopy (SEM). Extracellular matrix (ECM) elements and cell numbers were quantified biochemically. Mechanical properties were assessed by tensile testing. CD133- derived cells demonstrated characteristics of mesenchymal progenitors expressing CD44 and CD105. Differentiated CD133+ cells showed features of functional endothelial cells by eNOS and CD141 expression. Engineered heart valve leaflets demonstrated endothelialized tissue formation with production of ECM elements (GAG 80%, HYP 5%, cell number 100% of native values). SEM showed intact endothelial surfaces. Opening and closing behavior was sufficient under half of systemic conditions. CONCLUSIONS: The use of amniotic fluid as single cell source is a promising low risk approach enabling the prenatal fabrication of heart valves ready to use at birth. These living replacements with the potential of growth, remodeling, and regeneration may realize the early repair of congenital malformations. PMID- 17846328 TI - Intracoronary administration of AdvFGF-5 (fibroblast growth factor-5) ameliorates left ventricular dysfunction and prevents myocyte loss in swine with developing collaterals and ischemic cardiomyopathy. AB - BACKGROUND: Fibroblast growth factor (AdvFGF-5) improves regional function by stimulating myocyte hypertrophy without increasing myocardial perfusion in swine with hibernating myocardium. We performed the present study to determine whether AdvFGF-5 could prevent the progression of LV dysfunction in swine with ischemic cardiomyopathy. METHODS AND RESULTS: Swine were chronically instrumented with LAD and LCX stenoses to produce viable dysfunctional myocardium and studied 1 month after instrumentation in the closed-chest sedated state. Flow and regional function before and 30 days after intracoronary AdvFGF-5 (2x10(12) vp, n=9) were compared with animals receiving intracoronary AdvEGFP (2x10(12) vp, n=6). Histological analysis was performed to quantify myocyte size, myocyte nuclear density, apoptosis (TUNEL), and the frequency of myocytes in the proliferative phase of the cell cycle (Ki-67 staining). LAD wall-thickening (27+/-3 to 46+/-6%, P<0.05) and EF (39+/-4 to 56+/-3%, P<0.05) increased after AdvFGF-5. AdvFGF-5 increased maximal perfusion during adenosine vasodilation despite no differences in baseline flow or stenosis severity. After AdvFGF-5, TUNEL-positive myocytes decreased 6-fold and Ki-67 positive myocyte nuclei increased 2-fold. As a result, AdvFGF-5 produced a marked increase in myocyte nuclear density (957+/-54 to 1447+/-40 nuclei/mm2, P<0.05). CONCLUSION: These data indicate that AdvFGF-5 increases regional function and maximal perfusion distal to stenotic arteries when administered before the development of collaterals. This was associated with a reduction in myocyte apoptosis, an increase in Ki-67-positive myocytes, and an increase in myocyte number. Thus, AdvFGF-5 offers a potential therapeutic approach to prevent the progression of ischemic cardiomyopathy and heart failure. PMID- 17846329 TI - c-kit dysfunction impairs myocardial healing after infarction. AB - BACKGROUND: We hypothesized that c-kit receptor function in the bone marrow is important for facilitating healing, leading to efficient cardiac repair after myocardial infarction (MI). METHODS AND RESULTS: We used Kit(W)/Kit(W-v) c-kit mutant mice and their wild-type littermates to assess the importance of c-kit function in cardiac remodeling after coronary ligation. We found that mutant mice developed 1.6-fold greater ventricular dilation (P=0.008) attributable to a 1.3 fold greater infarct expansion by day 14 after MI (P=0.01). The number of proliferating smooth muscle alpha-actin expressing cells was 1.8-fold lower in mutant mice at day 3 (P<0.01), resulting in a 1.6 to 1.8-fold reduction in total regional nonvascular smooth muscle alpha-actin expressing cells by both microscopy and flow cytometry (P<0.001 for both). This decrease was accompanied by a 1.4-fold reduction in the number of CD31 expressing blood vessels (P<0.05). Prior transplantation of wild-type bone marrow cells into mutant mice rescued the efficient establishment of vessel-rich repair tissue by inducing a 1.5-fold increase in nonvascular smooth muscle alpha-actin expressing cells and CD31 expressing blood vessels (P<0.05 for both). The increased recruitment of cells into the infarct region in the chimeric mice was associated with reduced infarct expansion (P<0.03) compared to wild-type levels. CONCLUSIONS: Bone marrow c-kit function critically impacts the myofibroblast repair response in infarcted hearts. Interventions that increase the infiltration of c-kit+ cells to the infarcted heart may potentiate this endogenous repair response, prevent infarct expansion, and improve the recovery of cardiac function after MI. PMID- 17846330 TI - Hemodynamic and exercise performance with pulsatile and continuous-flow left ventricular assist devices. AB - BACKGROUND: Continuous-flow rotary pumps with axial design are increasingly used for left ventricular assist support. The efficacy of this design compared with pulsatile, volume displacement pumps, with respect to characteristics of left ventricular unloading, and exercise performance remains largely unstudied. METHODS AND RESULTS: Thirty-four patients undergoing implantation with a pulsatile, volume displacement pump operating in a full-to-empty cycle (HeartMate XVE; Thoratec Inc, Pleasanton, Calif; n=16) or continuous-flow rotary pump with an axial design operating at a fixed rotor speed (HeartMate II; Thoratec Inc; n=18) were evaluated with right heart catheterization and echocardiography preoperatively and at 3 months postoperatively and cardiopulmonary exercise testing 3 months postoperatively. Support with either the XVE or II resulted in significant (P<0.05) increases in cardiac output and reduction in mean pulmonary artery and pulmonary wedge pressures. Exercise capacity at 3 months was similar between groups (% predicted peak VO2-XVE: 46.8+/-10.2 versus II: 49.1+/-13.6). Echocardiography at 3 months demonstrated a significantly (P<0.05) greater reduction in left ventricular end-diastolic volume (-49+/-16% versus -35+/-20%), left ventricular end-systolic volume (-59+/-20 versus -37+/-21%), and percent mitral valve regurgitant volume (-99+/-2% versus -52+/-56%) for the XVE compared with II, respectively. CONCLUSIONS: The HeartMate XVE or II provided equivalent degrees of hemodynamic support and exercise capacity. The XVE was associated with greater left ventricular volume unloading. Characteristics of left ventricular pressure and volume unloading between these pump designs and mode of operation do not influence early exercise performance. PMID- 17846331 TI - Beneficial effects of complement inhibition with soluble complement receptor 1 (TP10) during cardiac surgery: is there a gender difference? AB - BACKGROUND: TP10, a potent inhibitor of complement activation during cardiopulmonary bypass (CPB) has been shown to significantly reduce the incidence of death and myocardial infarction (MI) in high-risk male patients undergoing cardiac surgery. However, the effect of TP10 in females was undefined because of the limited number of females studied. To examine the possibility of a gender effect, this phase 2 multi-center trial was undertaken to determine whether TP10 would also limit ischemic damage in a larger sample size of high-risk females undergoing cardiac surgery on cardiopulmonary bypass (CPB). METHODS AND RESULTS: This prospective, double-blind, placebo-controlled, multi-center trial involved 297 high-risk (urgent surgery, CABG + Valve, reoperations, ejection fraction <30%) female patients randomized to receive a 5 mg/kg dose of TP10 (n=150) or placebo (n=147) as a 30-minute intravenous infusion before surgery. The primary end point was the incidence of death or MI at 28 days after surgery. Complement activation was assessed by levels of CH50 and SC5b-9 during and after CPB. TP10 was well tolerated and there were no differences in the safety profiles of the 2 groups. Although TP10 effectively suppressed complement activation (at 2 hours after CPB CH50 (mean+SD % change from baseline) 50+/-17% placebo versus 4+/-14% TP10; P=0.0001; SC5b-9 (ng/mL) 917+/-1067 placebo versus 204+/-79 TP10; P=0.0001), there was no difference in the primary end point between the groups (17% placebo versus 21% TP10; P=0.2550). CONCLUSIONS: The benefits of TP10 appear to be gender-related. and mechanisms other than complement activation may be responsible for myocardial injury in high-risk female patients during cardiac surgery on CPB. PMID- 17846332 TI - The cardiotomy trial: a randomized, double-blind study to assess the effect of processing of shed blood during cardiopulmonary bypass on transfusion and neurocognitive function. AB - BACKGROUND: Reinfusion of unprocessed cardiotomy blood during cardiac surgery can introduce particulate material into the cardiopulmonary bypass circuit, which may contribute to postoperative cognitive dysfunction. On the other hand, processing of this blood by centrifugation and filtration removes coagulation factors and may potentially contribute to coagulopathy. We sought to evaluate the effects of cardiotomy blood processing on blood product use and neurocognitive functioning after cardiac surgery. METHODS AND RESULTS: Patients undergoing coronary and/or aortic valve surgery using cardiopulmonary bypass were randomized to receive unprocessed blood (control, n=134) or cardiotomy blood that had been processed by centrifugal washing and lipid filtration (treatment, n=132). Patients and treating physicians were blinded to treatment assignment. A strict transfusion protocol was followed. Blood transfusion data were analyzed using Poisson regression models. The treatment group received more intraoperative red blood cell transfusions (0.23+/-0.69 U versus 0.08+/-0.34 U, P=0.004). Both red blood cell and nonred blood cell blood product use was greater in the treatment group and postoperative bleeding was greater in the treatment group. Patients were monitored intraoperatively by transcranial Doppler and they underwent neuropsychometric testing before surgery and at 5 days and 3 months after surgery. There was no difference in the incidence of postoperative cognitive dysfunction in the 2 groups (relative risk: 1.16, 95% CI: 0.86 to 1.57 at 5 days postoperatively; relative risk: 1.05, 95% CI: 0.58 to 1.90 at 3 months). There was no difference in the quality of life nor was there a difference in the number of emboli detected in the 2 groups. CONCLUSIONS: Contrary to expectations, processing of cardiotomy blood before reinfusion results in greater blood product use with greater postoperative bleeding in patients undergoing cardiac surgery. There is no clinical evidence of any neurologic benefit with this approach in terms of postoperative cognitive function. PMID- 17846333 TI - Remote ischemic preconditioning reduces myocardial and renal injury after elective abdominal aortic aneurysm repair: a randomized controlled trial. AB - BACKGROUND: Myocardial and renal injury commonly contribute to perioperative morbidity and mortality after abdominal aortic aneurysm repair. Remote ischemic preconditioning (RIPC) is a phenomenon whereby brief periods of ischemia followed by reperfusion in one organ provide systemic protection from prolonged ischemia. To investigate whether remote preconditioning reduces the incidence of myocardial and renal injury in patients undergoing elective open abdominal aortic aneurysm repair, we performed a randomized trial. METHOD AND RESULTS; Eighty-two patients were randomized to abdominal aortic aneurysm repair with RIPC or conventional abdominal aortic aneurysm repair (control). Two cycles of intermittent crossclamping of the common iliac artery with 10 minutes ischemia followed by 10 minutes reperfusion served as the RIPC stimulus. Myocardial injury was assessed by cardiac troponin I (>0.40 ng/mL), myocardial infarction by the American College of Cardiology/American Heart Association definition and renal injury by serum creatinine (>177 micromol/L) according to American Heart Association guidelines for risk stratification in major vascular surgery. The groups were well matched for baseline characteristics. RIPC reduced the incidence of myocardial injury by 27% (39% versus 12% [95% CI: 8.8% to 45%]; P=0.005), myocardial infarction by 22% (27% versus 5% [95% CI: 7.3% to 38%]; P=0.006), and renal impairment by 23% (30% versus 7%; [95% CI: 6.4 to 39]; P=0.009). Multivariable analysis revealed the protective effect of RIPC on myocardial injury (OR: 0.22, 95% CI: 0.07 to 0.67; P=0.008), myocardial infarction (OR: 0.18, 95% CI: 0.04 to 0.75; P=0.006) and renal impairment were independent of other covariables. CONCLUSIONS: In patients undergoing elective open abdominal aortic aneurysm repair, RIPC reduces the incidence of postoperative myocardial injury, myocardial infarction, and renal impairment. PMID- 17846334 TI - Spotlight: Keith A. A. Fox, FRCP, FESC, FMedSci. Interview by Judy Ozkan. PMID- 17846335 TI - Cardiology patient page. Natural bypasses can save lives. PMID- 17846336 TI - Images in cardiovascular medicine. Cardiac tamponade with fibrin strands leading to the diagnosis of systemic lupus erythematosus. PMID- 17846337 TI - Images in cardiovascular medicine. Retroperitoneal hematoma after inferior vena cava filter insertion. PMID- 17846338 TI - Letter by Guarracino et al regarding article, "Direct myocardial effects of levosimendan in humans with left ventricular dysfunction: alteration of force frequency and relaxation-frequency relationships". PMID- 17846339 TI - Increased endoplasmic reticulum stress in atherosclerotic plaques associated with acute coronary syndrome: a balancing act between plaque stability and rupture. PMID- 17846340 TI - Significance of circulating troponins in heart failure: if these walls could talk. PMID- 17846341 TI - Endothelium-derived bone morphogenic protein antagonists may counteract the proatherogenic vascular effects of bone morphogenic protein 4. PMID- 17846342 TI - Coronary microvasculopathy after heart transplantation: a new marker to guide future trials? PMID- 17846343 TI - Radiation dose to patients from cardiac diagnostic imaging. PMID- 17846344 TI - To drink or not to drink? That is the question. AB - Numerous studies have used a J-shaped or U-shaped curve to describe the relationship between alcohol use and total mortality. The nadir of the curves based on recent meta-analysis suggested optimal benefit at approximately half a drink per day. Fewer than 4 drinks per day in men and fewer than 2 per day in women appeared to confer benefit. Reductions in cardiovascular death and nonfatal myocardial infarction were also associated with light to moderate alcohol intake. Although some studies suggested that wine had an advantage over other types of alcoholic beverages, other studies suggested that the type of drink was not important. Heavy drinking was associated with an increase in mortality, hypertension, alcoholic cardiomyopathy, cancer, and cerebrovascular events, including cerebrovascular hemorrhage. Paradoxically, light-to-moderate alcohol use actually reduced the development of heart failure and did not appear to exacerbate it in most patients who had underlying heart failure. Numerous mechanisms have been proposed to explain the benefit that light-to-moderate alcohol intake has on the heart, including an increase of high-density lipoprotein cholesterol, reduction in plasma viscosity and fibrinogen concentration, increase in fibrinolysis, decrease in platelet aggregation, improvement in endothelial function, reduction of inflammation, and promotion of antioxidant effects. Controversy exists on whether alcohol has a direct cardioprotective effect on ischemic myocardium. Studies from our laboratory do not support the concept that alcohol has a direct cardioprotective effect on ischemic/reperfused myocardium. Perhaps the time has come for a prospectively randomized trial to determine whether 1 drink per day (or perhaps 1 drink every other day) reduces mortality and major cardiovascular events. PMID- 17846345 TI - Unexpected therapeutic response to spironolactone: a prospective debate on aldosterone and potassium ion in hypertension. PMID- 17846346 TI - Association of increased plasma cardiotrophin-1 with inappropriate left ventricular mass in essential hypertension. AB - Inappropriate left ventricular mass is present when the value of left ventricular mass exceeds individual needs to compensate hemodynamic load imposed by increased blood pressure. The goal of this study was to investigate whether plasma concentration of cardiotrophin-1, a cytokine that induces exaggerated hypertrophy in cardiomyocytes with hypertensive phenotype, is related to inappropriate left ventricular mass in patients with essential hypertension. The study was performed in 118 patients with never-treated hypertension and without prevalent cardiac disease. The left ventricular mass prediction from stroke work (systolic blood pressurexDoppler stroke volume), sex, and height (in meters(2.7)) was derived. An observed left ventricular mass/predicted left ventricular mass value >128% defined inappropriate left ventricular mass. Plasma cardiotrophin-1 was measured by an enzyme-linked immunosorbent assay. The studies were repeated in a group of 45 patients after 1 year of antihypertensive treatment. At baseline 67 and 51 patients presented with appropriate and inappropriate left ventricular mass, respectively. Plasma cardiotrophin-1 was higher (P<0.001) in patients with inappropriate mass than in patients with appropriate mass and normotensive controls. A direct correlation was found between cardiotrophin-1 and observed left ventricular mass/predicted left ventricular mass ratio (r=0.330, P<0.001) in all hypertensive patients. After treatment, plasma cardiotrophin-1 decreased and increased in patients in which inappropriate left ventricular mass regressed and persisted, respectively, despite a similar reduction of blood pressure in the 2 subgroups of patients. Albeit descriptive in nature, these results suggest the hypothesis that an excess of cardiotrophin-1 may contribute to inappropriate left ventricular growth in hypertensive patients. PMID- 17846347 TI - Acarbose and postprandial hypotension. PMID- 17846348 TI - Renin enhancer is crucial for full response in Renin expression to an in vivo stimulus. AB - We showed recently that deletion of a strong enhancer located 2.7 kb upstream of the renin gene in mice produces a strain with mild hypotension and salt sensitivity. Here we set out to compare responses in renin expression in kidney and extrarenal tissues in these "REKO" mice. REKO and wild-type mice were placed on a low NaCl/enalapril regimen for 1 week, and then Ren-1(c) mRNA and renin enzyme activities were measured in tissues and plasma. In untreated REKO mice, renin and Ren-1(c) mRNA were reduced significantly in kidney, submandibular gland, adrenal, heart, and brain. In situ hybridization indicated a marked reduction in Ren-1(c) mRNA in juxtaglomerular cells and granular ducts of submandibular gland. After the chronic stimulus response in renal Ren-1(c) mRNA in REKO mice was blunted by 54% compared with wild-type mice, and was accompanied by almost complete exhaustion of renin stores. Response in plasma renin was blunted by 47%, this being mirrored in heart (54% decline), in which renin is derived mostly from the bloodstream. In adrenal a 55% reduction was seen. These data are consistent with inability of REKO mice to adequately replenish renal renin stores during chronic stimulation of renin secretion. In conclusion, the renin enhancer is critical for replenishment of renin stores and response in renin to a chronic in vivo stimulus. PMID- 17846349 TI - Chronic baroreceptor activation enhances survival in dogs with pacing-induced heart failure. AB - Much of the current pharmacological therapy for chronic heart failure targets neurohormonal activation. In spite of recent advances in drug therapy, the mortality rate for chronic heart failure remains high. Activation of the carotid baroreceptor (BR) reduces sympathetic outflow and augments vagal tone. We investigated the effect of chronic activation of the carotid BR on hemodynamic and neurohormonal parameters and on mortality in dogs with chronic heart failure. Fifteen dogs were instrumented to record hemodynamics. Electrodes were applied around the carotid sinuses to allow for activation of the BR. After 2 weeks of pacing (250 bpm), electrical carotid BR activation was initiated in 7 dogs and continued for the remainder of the study. The start of BR activation was used as a time reference point for the remaining 8 control dogs that did not receive BR activation. Survival was significantly greater for dogs undergoing carotid BR activation compared with control dogs (68.1+/-7.4 versus 37.3+/-3.2 days, respectively; P<0.01), although arterial pressure, resting heart rate, and left ventricular pressure were not different over time in BR-activated versus control dogs. Plasma norepinephrine was lower in dogs receiving BR activation therapy 31 days after the start of BR activation (401.9+/-151.5 versus 1121.9+/-389.1 pg/mL in dogs not receiving activation therapy; P<0.05). Plasma angiotensin II increased less in dogs receiving activation therapy (plasma angiotensin II increased by 157.4+/-58.6 pg/mL in control dogs versus 10.1+/-14.0 pg/mL in dogs receiving activation therapy; P<0.02). We conclude that chronic activation of the carotid BR improves survival and suppresses neurohormonal activation in chronic heart failure. PMID- 17846351 TI - Extracellular renal guanosine cyclic 3'5'-monophosphate modulates nitric oxide and pressure-induced natriuresis. AB - This study addresses the hypothesis that NO- and pressure-induced natriuresis are inhibited when guanosine cyclic 3',5'-monophosphate (cGMP) is prevented from being transported outside its renal synthesizing cells in vivo. Rats received a renal interstitial (RI) infusion of NO donor S-nitroso-N-acetylpenicillamine (SNAP) or SNAP+organic anion transporter inhibitor probenecid (PB) or SNAP+PB+cGMP. SNAP alone increased U(Na)V (P<0.05 at 1 hour and P<0.005 at 2 hours). In contrast, SNAP failed to increase U(Na)V when coinfused with PB, but cGMP coinfused with SNAP+probenecid restored the natriuretic response. SNAP alone increased RI cGMP (P<0.05) during the second experimental period. PB abolished the increase in RI cGMP in response to SNAP (P<0.01), but cGMP levels were restored by coinfusion with cGMP. PB also abolished SNAP-induced increases in fractional excretion of Na(+) (FE(Na)) and lithium (FE(Li)) (both P<0.01). PB also abolished the rise in RI cGMP and natriuresis induced by raising renal perfusion pressure (RPP) from 100 to 160 mm Hg in rats subjected to a standard pressure-natriuresis protocol and the natriuretic response was rescued by coinfusion with cGMP. RI administration of phosphodiesterase type V (PDE V) reduced both RIcGMP and U(Na)V in parallel (both P<0.01) without altering RIcAMP. The data demonstrate that export of cGMP from its renal synthesizing cells into the extracellular RI compartment is critical for the natriuretic action of NO donor SNAP or increased RPP and that RI cGMP controls basal Na(+) excretion. Extracellular cGMP modulates NO- and pressure-induced natriuresis. PMID- 17846350 TI - Mineralocorticoid receptor blockade improves vasomotor dysfunction and vascular oxidative stress early after myocardial infarction. AB - Mineralocorticoid receptor blockade improves mortality early after myocardial infarction (MI). This study investigated the vascular effects of mineralocorticoid receptor blockade in the early phase postinfarction in rats. Starting immediately after coronary ligation, male Wistar rats were treated with placebo or eplerenone (100 mg/kg/d). After 7 days, hemodynamic assessment was performed and endothelial function was determined. Maximum acetylcholine-induced relaxation was significantly attenuated in aortic rings from rats with heart failure after MI, and ameliorated by eplerenone treatment. Endothelium independent relaxation by DEA-NONOate was similar among the groups. Endothelial NO synthase phosphorylation was reduced in the aorta of MI rats and restored by eplerenone therapy. Angiotensin I-induced vasoconstriction as well as angiotensin converting enzyme protein levels were enhanced in aortas from MI placebo rats, and reduced by mineralocorticoid receptor inhibition. Aortic reactive oxygen species formation as well as the expression of the NAD(P)H oxidase subunit p22(phox) were increased after MI and normalized in eplerenone treated rats. In conclusion, mineralocorticoid receptor antagonism improved endothelial dysfunction in the early phase post-MI. Underlying mechanisms involve inhibition of vascular angiotensin-converting enzyme upregulation and improvement of endothelial NO synthase-derived NO bioavailability. PMID- 17846352 TI - Blood pressure control in Hispanics in the antihypertensive and lipid-lowering treatment to prevent heart attack trial. AB - Historically, blood pressure control in Hispanics has been considerably less than that of non-Hispanic whites and blacks. We compared determinants of blood pressure control among Hispanic white, Hispanic black, non-Hispanic white, and non-Hispanic black participants (N=32 642) during follow-up in a randomized, practice-based, active-controlled trial. Hispanic blacks and whites represented 3% and 16% of the cohort, respectively; 33% were non-Hispanic black and 48% were non-Hispanic white. Hispanics were less likely to be controlled (<140/90 mm Hg) at enrollment, but within 6 to 12 months of follow-up, Hispanics had a greater proportion <140/90 mm Hg compared with non-Hispanics. At 4 years of follow-up, blood pressure was controlled in 72% of Hispanic whites, 69% of Hispanic blacks, 67% of non-Hispanic whites, and 59% of non-Hispanic blacks. Compared with non Hispanic whites, Hispanic whites had a 20% greater odds of achieving BP control by 2 years of follow-up (odds ratio: 1.20; 95% CI: 1.10 to 1.31) after controlling for demographic variables and comorbidities, Hispanic blacks had a similar odds of achieving BP control (odds ratio: 1.04; 95% CI: 0.86 to 1.25), and non-Hispanic blacks had a 27% lower odds (odds ratio: 0.73; 95% CI: 0.69 to 0.78). We conclude that in all patients high levels of blood pressure control can be achieved with commonly available medications and that Hispanic ethnicity is not associated with inferior control in the setting of a clinical trial in which hypertensive patients had equal access to medical care, and medication was provided at no cost. PMID- 17846353 TI - Safety and efficacy assessment of chimeric ribozyme to proliferating cell nuclear antigen to prevent recurrence of proliferative vitreoretinopathy. AB - OBJECTIVE: To determine the safety and efficacy of VIT100 (Immusol, Inc, San Diego, California), a ribozyme to proliferating cell nuclear antigen, in preventing recurrent proliferative vitreoretinopathy (PVR) in patients with established PVR who undergo vitrectomy for retinal reattachment repair. METHODS: A multicenter, double-masked, placebo-controlled, randomized clinical trial. One hundred seventy-five eyes from 175 patients with grade C or worse PVR were randomly assigned to receive high-dose VIT100, low-dose VIT100, or placebo by intravitreal injection at the conclusion of retinal reattachment surgery. MAIN OUTCOME MEASURES: The primary efficacy end point was recurrent retinal detachment secondary to PVR. The secondary end point was recurrent retinal detachment due to any cause. RESULTS: One hundred fifty-four patients completed the study. Forty one patients (27%) developed recurrent retinal detachment due to PVR by 24 weeks, including 18 patients (33%) in the group receiving 0.75 mg, 13 patients (24%) in the group receiving 0.15 mg, and 10 patients (22%) in the placebo group. There was no statistically significant difference in patients reaching this end point by 24 weeks (P = .37). Ancillary statistical analyses are reported. CONCLUSIONS: VIT100 was not effective in preventing PVR recurrence in patients with established grade C or worse PVR. APPLICATION TO CLINICAL PRACTICE: To our knowledge, this is the most recent, meticulously designed clinical trial in PVR. PMID- 17846354 TI - In vivo laser confocal microscopic findings of corneal stromal dystrophies. AB - OBJECTIVE: To investigate in vivo laser confocal microscopic findings of genetically mapped corneal stromal dystrophies and their relationship to histopathologic findings. METHODS: Seven patients with Avellino corneal dystrophy, 2 patients with lattice corneal dystrophy, and 2 patients with macular corneal dystrophy were examined genetically and using slitlamp biomicroscopy and in vivo laser confocal microscopy. Corneal specimens obtained after surgery in selected patients were histopathologically studied. RESULTS: In Avellino corneal dystrophy (Arg124His mutation of human transforming growth factor beta-induced gene [TGFBI]), highly reflective granular materials with irregular edges were observed in the superficial stroma. In lattice corneal dystrophy (Arg124Cys and Leu527Arg mutations of TGFBI), highly reflective branching filaments of variable width were observed in the stroma. In macular corneal dystrophy (Ala217Thr mutation of the carbohydrate sulfotransferase gene [CHST6]), homogeneous reflective materials with dark striaelike images were observed throughout the stroma. All confocal findings correlated well with histopathologic findings. CONCLUSIONS: In vivo laser confocal microscopy is capable of high-resolution visualization of characteristic corneal microstructural changes related to 3 types of genetically mapped corneal stromal dystrophies. The use of laser confocal microscopy may be valuable in the differential diagnosis of corneal stromal dystrophies, especially when diagnosis is otherwise uncertain. PMID- 17846355 TI - Comparison of methods to predict visual field progression in glaucoma. AB - OBJECTIVE: To compare performance of pointwise linear regression, Glaucoma Change Probability Analysis (GCPA), and the Advanced Glaucoma Intervention Study (AGIS) method in predicting visual field progression in glaucoma. DESIGN: Longitudinal visual field data from AGIS. Proportion of progressing eyes and time to progression were the main outcome measures. One hundred fifty-six patients with 8 or more years of follow-up were included. Prediction of outcomes at 8 years was used to evaluate the performance of each method (pointwise linear regression, GCPA, and AGIS). RESULTS: Visual field progression at 8 years was detected in 35%, 31%, and 22% of patients by pointwise linear regression, GCPA, and the AGIS method, respectively. Baseline mean deviation was not different for nonprogressing vs progressing eyes for all methods (P > .05). Pointwise linear regression and GCPA had the highest pairwise concordance (kappa = 0.58 [SD, 0.07]). The false prediction rates at 4 and 8 years varied between 1% and 3%. Glaucoma Change Probability Analysis predicted final outcomes better than pointwise linear regression at 4 years (P = .001). CONCLUSIONS: All algorithms had low false prediction rates. Glaucoma Change Probability Analysis predicted outcomes better than pointwise linear regression early during follow-up. Algorithms did not perform differently as a function of baseline damage. Pointwise linear regression and GCPA did not agree well regarding spatial distribution of worsening test locations. PMID- 17846356 TI - Association between cultures of contact lens and corneal scraping in contact lens related microbial keratitis. AB - OBJECTIVE: To study the association between cultures of contact lens and corneal scraping in contact lens-related microbial keratitis. METHODS: A retrospective analysis of the culture results of corneal scrapings and contact lenses of patients with contact lens-related microbial keratitis who were initially seen at Royal Victorian Eye and Ear Hospital, Melbourne, Australia, between January 1, 2001, and December 31, 2004, was conducted. RESULTS: Fifty eye specimens of 49 patients were included in the study. Corneal scrapings and contact lenses were culture positive in 17 eyes (34%) and in 35 eyes (70%), respectively. In 13 eyes, corneal scrapings and contact lenses yielded identical organisms. Serratia marcescens was the most common organism isolated from the corneal scrapings and from the contact lenses. CONCLUSION: Contact lens culture may sometimes give a clue to the organism involved in cases of microbial keratitis in which the corneal scraping is culture negative and may help in choosing the appropriate antimicrobial therapy. PMID- 17846357 TI - Internal en bloc resection and genetic analysis of retinal capillary hemangioblastoma. AB - OBJECTIVE: To report the clinical outcomes and molecular genetics of nongermline retinal hemangioblastoma managed by surgical resection. METHODS: Retrospective case series of 3 patients aged 16 to 46 years treated at a tertiary care referral center (Casey Eye Institute, Portland, Oregon). Tumors 7 to 9 mm in diameter were removed from 3 consecutive eyes (in 3 patients) via internal en bloc surgical resection using a bimanual technique. Samples of DNA from 2 of 3 tumors were tested for von Hippel-Lindau gene (VHL) mutations as a clue to the molecular basis for spontaneously occurring hemangioblastoma. Main outcome measures were morbidity, visual acuity, resolution of macular exudates, and presence of VHL markers. RESULTS: Visual acuity improved or remained stable in all patients. All 3 developed cataracts, extracted in 2 instances. Histopathological findings were typical of retinal hemangioblastoma in all cases. The cells from one patient's DNA sample showed loss of heterozygosity for the VHL gene, while no genetic abnormalities were detected in the other patient's DNA sample. CONCLUSIONS: Our patients' favorable outcomes suggest that surgical resection is an option for patients with large retinal hemangioblastomas. In addition, ours may be the first report of retinal hemangioblastoma unassociated with a VHL mutation. PMID- 17846358 TI - Loss of photoreceptor outer segment in acute zonal occult outer retinopathy. AB - OBJECTIVE: To describe retinal changes in acute zonal occult outer retinopathy (AZOOR). METHODS: We investigated retinal function and morphologic changes in 5 patients (mean age, 33.6 years) with AZOOR and acute visual field loss in 1 or more zones using Stratus optical coherence tomography, multifocal electroretinograms, full-field electroretinograms, and Goldmann perimetry. RESULTS: Goldmann perimetry showed enlarged blind spots of Mariotte bilaterally in 2 patients and unilaterally in 3 patients. Another scotoma was seen in the nasal paracentral area, the inferior midperiphery, and centrally. No visible retinal lesions corresponded to these scotomas except for inferior midperipheral retinal pigment epithelium atrophy and peripapillary depigmented lesions. The multifocal electroretinograms showed a markedly decreased response from the blind spots and scotomas. Optical coherence tomography showed loss or irregularity of the inner segment-outer segment line in the areas of decreased response on multifocal electroretinography and those with visual field defects. The outer nuclear layer disappeared in 2 cases. Areas of visible retinal pigment epithelium atrophy showed an irregular retinal pigment epithelial reflex, increased choroidal reflectivity, and retinal attenuation. CONCLUSIONS: Photoreceptor outer segment dysfunction and/or degeneration seem to be the primary lesion in AZOOR. Optical coherence tomography is an important tool for detecting morphologic changes in this occult retinopathy. PMID- 17846359 TI - Plaque radiotherapy for choroidal melanoma encircling the optic disc (circumpapillary choroidal melanoma). AB - OBJECTIVE: To report results of plaque radiotherapy for choroidal melanoma that completely encircles the optic disc (circumpapillary melanoma). METHODS: Retrospective medical record review over a 31-year period of 37 consecutive patients. The main outcome measures were treatment complications, long-term visual acuity, enucleation, tumor recurrence, metastasis, and death. RESULTS: The median patient age at treatment was 69 years (range, 20-86 years). The presenting complaint was visual loss in 19 eyes (51%), photopsia in 5 (14%), and visual field loss in 3 (8%). All tumors touched and encircled the optic disc for 360 degrees . The quadrantic location of the main tumor epicenter was superior in 8 eyes (22%), nasal in 10 (27%), inferior in 9 (24%), and temporal in 10 (27%). The median tumor basal diameter was 11 mm (range, 4.8-20 mm) and median tumor thickness was 3.6 mm (range, 1.8-14.8 mm). The optic disc was obscured to some extent by overhanging tumor in 19 cases (52%). The most commonly used isotope for plaque radiotherapy was iodine 125 (n = 34 cases; 92%), and a notched plaque design was used in 34 cases (92%). Planned adjunctive treatment included transpupillary thermotherapy in 17 cases (49%) and argon laser photocoagulation in 6 of 35 cases (17%) with follow-up. Of the 28 eyes with more than 5 months' follow-up (mean, 52 months; median, 46 months; range, 5-234 months), treatment complications included nonproliferative and proliferative retinopathy in 11 (39%) and 7 eyes (25%); maculopathy in 7 (25%); papillopathy in 9 eyes (32%); neovascular glaucoma in 5 (18%); and vitreous hemorrhage in 13 (46%). Pars plana vitrectomy was required in only 2 of 13 eyes (15%) with persistent vitreous hemorrhage. Long-term visual acuity of 20/200 or worse was observed in 13 eyes (62%), and 12 eyes (57%) lost more than 5 Snellen visual acuity lines, excluding 7 cases (25%) in which enucleation was necessary. Recurrence was noted in 4 cases (14%), of which 3 were treated with enucleation and 1 with transpupillary thermotherapy. Systemic metastasis occurred in 1 patient (4%) and there were no melanoma-specific deaths during the study period. CONCLUSIONS: Custom-designed plaque radiotherapy is a potential treatment for selected patients with circumpapillary choroidal melanoma. We found satisfactory local tumor control, and globe retention was achieved in 75% of eyes with more than 5 months' follow up. PMID- 17846360 TI - Management of nonresolving consecutive exotropia following botulinum toxin treatment of childhood esotropia. AB - OBJECTIVE: To study motor and sensory results of surgery for exotropia following botulinum toxin A injection to correct childhood esotropia. METHODS: The medical records of 2445 patients treated with botulinum toxin bimedial injection were retrospectively reviewed to select patients operated on after 1 year of consecutive exotropia. We recorded age at onset of deviation, retinoscopic refractive error, visual acuity and age and dosage at the time of botulinum toxin injection. Retinoscopic refractive error, visual acuity, deviation angle, and stereoacuity before surgery for consecutive exotropia were also recorded. Families were contacted to obtain retinoscopic refraction, visual acuity, deviation angle, Bagolini test, vectography, and stereoacuity data 1 to 8 years after surgery. RESULTS: A total of 5 children with acquired esotropia and 2 with infantile esotropia were included. A high dose of the toxin per injection might increase the risk of consecutive esotropia. Preoperative mean exotropic deviation was 15.42 prism diopters (PD) (range, 10-25 PD), and stereoacuity was not measurable before surgery. Postoperative mean deviation was 6 PD (range, 4-8 PD), and mean stereoacuity was 447.14 arc seconds. In 2 patients, suppression of the nondominant eye was detected. Three children had poor stereoacuity. CONCLUSION: Surgery for exotropia following botulinum toxin injection in children is effective from a motor and sensory point of view. PMID- 17846361 TI - The resident surgeon phacoemulsification learning curve. AB - OBJECTIVES: To analyze outcomes of resident-performed phacoemulsifications and to assess the resident phacoemulsification learning curve. METHODS: Retrospective chart review of resident-performed phacoemulsification cases at the Atlanta Veterans Affairs Medical Center, Decatur, Georgia, from July 1, 1999, through June 30, 2002. Outcomes measured included postoperative uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), intraoperative complications, and adjusted phacoemulsification times (total phacoemulsification time multiplied by phacoemulsification power used). RESULTS: We analyzed 680 cases. Postoperative mean UCVA was 20/39, and mean BSCVA was 20/25 (> or = 20/20 in 44.0% of cases and > or = 20/40 in 97.8%). There were no differences in visual acuity outcomes over the course of residency training. Intraoperative complications occurred in 34 cases (5.0%), with a significant reduction in vitreous loss rates after the first 80 resident cases (5.1% vs 1.9%; P = .03). Mean adjusted phacoemulsification time was 0.68 minutes, with a significant reduction in adjusted phacoemulsification time after the first 80 cases (0.87 vs 0.52 minutes; P < .001). CONCLUSIONS: Quality visual outcomes after phacoemulsification can be attained throughout residency training; however, surgical competency, when measured by complication rates and phacoemulsification efficiency, continues to improve significantly with increasing surgical experience well beyond the first 80 resident phacoemulsification cases. PMID- 17846362 TI - Intravitreal infliximab and choroidal neovascularization in an animal model. AB - OBJECTIVE: To determine whether intravitreal infliximab can inhibit the growth of choroidal neovascularization (CNV) in an animal model of age-related macular degeneration. METHODS: Twenty-four brown Norway rats received 6 argon laser lesions of sufficient power to rupture the Bruch membrane in each eye. The right eye received a single intravitreal infliximab injection of 0.15 mg/mL, 1.5 mg/mL, or 15 mg/mL. The left eye received an injection of balanced saline solution. The animals were then euthanized at day 30, the eyes were enucleated, and the amount of CNV was quantified with digital analysis software. RESULTS: Intravitreal infliximab inhibited CNV growth in the rat laser-trauma model in a dose-response manner. In the 1.5-mg/mL group, there was an 11% reduction in CNV growth (P = .01). In the 15-mg/mL group, CNV growth was decreased by 68% (P < .001). CONCLUSIONS: Infliximab can inhibit CNV in a rat laser-trauma model, implicating its target cytokine tumor necrosis factor alpha in the angiogenic stimulus for CNV. Suppression of inflammatory cytokines may prove to be another therapeutic target in the treatment of exudative macular degeneration. Clinical Relevance This study demonstrates in a model of macular degeneration an antiangiogenic effect of intravitreal infliximab, which provides a rationale for future human studies. PMID- 17846363 TI - The relationship of dietary carotenoid and vitamin A, E, and C intake with age related macular degeneration in a case-control study: AREDS Report No. 22. AB - OBJECTIVE: To evaluate the relationship of dietary carotenoids, vitamin A, alpha tocopherol, and vitamin C with prevalent age-related macular degeneration (AMD) in the Age-Related Eye Disease Study (AREDS). METHODS: Demographic, lifestyle, and medical characteristics were ascertained on 4519 AREDS participants aged 60 to 80 years at enrollment. Stereoscopic color fundus photographs were used to categorize participants into 4 AMD severity groups and a control group (participants with < 15 small drusen). Nutrient intake was estimated from a self administered semiquantitative food frequency questionnaire at enrollment. Intake values were energy adjusted and classified by quintiles. The relationship between diet and AMD status was assessed using logistic regression analyses. RESULTS: Dietary lutein/zeaxanthin intake was inversely associated with neovascular AMD (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.45-0.93), geographic atrophy (OR, 0.45; 95% CI, 0.24-0.86), and large or extensive intermediate drusen (OR, 0.73; 95% CI, 0.56-0.96), comparing the highest vs lowest quintiles of intake, after adjustment for total energy intake and nonnutrient-based covariates. Other nutrients were not independently related to AMD. CONCLUSION: Higher dietary intake of lutein/zeaxanthin was independently associated with decreased likelihood of having neovascular AMD, geographic atrophy, and large or extensive intermediate drusen. PMID- 17846364 TI - Mitochondrial DNA haplogroups and age-related maculopathy. AB - OBJECTIVE: To investigate whether mitochondrial haplogroups are associated with age-related maculopathy (ARM). METHODS: We assessed the association between mitochondrial haplogroups and ARM in a population-based sample of 3509 persons aged 49 years or older residing west of Sydney. Retinal photographs of both eyes were taken (1999-2001) and subsequently graded for ARM following the Wisconsin grading system. Genetic analysis for mitochondrial DNA haplogroups was performed. Associations between these genetic markers and risk factors for ARM were assessed. RESULTS: After adjusting for age, sex, and smoking, haplogroup H was associated with a reduced prevalence of any (early and late) ARM (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.58-0.97), early ARM (OR, 0.75; 95% CI, 0.57-0.98), and large distinct and indistinct soft drusen (OR, 0.70; 95% CI, 0.56-0.89). Haplogroup J was associated with a higher prevalence of large, soft distinct drusen (OR, 1.80; 95% CI, 1.18-2.73). Haplogroup U was associated with an increased prevalence of retinal pigment abnormalities (OR, 1.45; 95% CI, 1.11 1.91). CONCLUSIONS: Our findings of associations between different haplogroup types and prevalent ARM or ARM lesions suggest that these haplogroups may be genetic markers indicative of an individual's susceptibility to ARM. PMID- 17846365 TI - Age-related macular degeneration and cancer mortality in the atherosclerosis risk in communities study. AB - OBJECTIVE: To examine the prospective association of early age-related macular degeneration (AMD) with cancer mortality. METHODS: A population-based cohort study of 10 029 persons aged 49 to 73 years free of cancer. The AMD signs were evaluated from retinal photographs taken in 1993 through 1995. Cancer mortality was determined from death records. RESULTS: There were 464 cases of early AMD. Over 10 years, there were 234 cancer deaths (71 lung cancer deaths). After controlling for age, sex, race, field center, education, smoking status, pack years of smoking, body mass index (calculated as weight in kilograms divided by height in meters squared), and diabetes mellitus, early AMD was associated with cancer mortality (rate ratio [RR], 1.68; 95% confidence interval [CI], 1.03 2.73). This association was overall stronger in African American individuals (RR, 3.93; 95% CI, 1.67-9.22) than white individuals (RR, 1.28; 95% CI, 0.71-2.32) and for lung cancer deaths (RR, 2.14; 95% CI, 0.97-4.72) than non-lung cancer deaths (RR, 1.50; 95% CI, 0.81-2.78). In African American individuals, early AMD was associated with a 5-fold higher risk of lung cancer deaths (RR, 5.28; 95% CI, 1.52-18.40). CONCLUSIONS: Middle-aged African American individuals with early AMD may be at increased risk of dying of cancer, particularly lung cancer. This association was not present in white individuals and needs confirmation in other studies. PMID- 17846366 TI - Burden and health care resource utilization in neovascular age-related macular degeneration: findings of a multicountry study. AB - OBJECTIVE: To describe the burden of bilateral neovascular age-related macular degeneration (NV-AMD) on patient-reported functioning and health resource utilization. METHODS: A cross-sectional study of 401 patients with bilateral NV AMD and 471 elderly control subjects without AMD was conducted in 5 countries. Subjects completed a telephone survey, including the National Eye Institute 25 Item Visual Function Questionnaire, the EuroQol instrument, the Hospital Anxiety and Depression Scale, and history of falls, fractures, and health care resource utilization. RESULTS: The mean age for patients with NV-AMD was 78.1 years, and 65% were women. The patients reported 45% worse vision-related functioning, 13% worse overall well-being, and 30% more anxiety and 42% more depression symptoms than controls after adjusting for covariates (all, P < .001). The effect of NV AMD was also observed as a doubled fall rate (16% vs 8% [P < .001]) and a quadrupled need for assistance with daily activities (29% vs 7% [P < .001]) in the patients compared with controls. CONCLUSIONS: The evidence of extensive decline in quality of life and increased need of daily living assistance for patients with NV-AMD compared with a control population substantiates the need for new treatments that prevent vision loss and progression to blindness. PMID- 17846367 TI - Allelic variation of the FRMD7 gene in congenital idiopathic nystagmus. AB - OBJECTIVES: To perform a genotype-phenotype correlation study in an X-linked congenital idiopathic nystagmus pedigree (pedigree 1) and to assess the allelic variance of the FRMD7 gene in congenital idiopathic nystagmus. METHODS: Subjects from pedigree 1 underwent detailed clinical examination including nystagmology. Screening of FRMD7 was undertaken in pedigree 1 and in 37 other congenital idiopathic nystagmus probands and controls. Direct sequencing confirmed sequence changes. X-inactivation studies were performed in pedigree 1. RESULTS: The nystagmus phenotype was extremely variable in pedigree 1. We identified 2 FRMD7 mutations. However, 80% of X-linked families and 96% of simplex cases showed no mutations. X-inactivation studies demonstrated no clear causal link between skewing and variable penetrance. CONCLUSIONS: We confirm profound phenotypic variation in X-linked congenital idiopathic nystagmus pedigrees. We demonstrate that other congenital nystagmus genes exist besides FRMD7. We show that the role of X inactivation in variable penetrance is unclear in congenital idiopathic nystagmus. Clinical Relevance We demonstrate that phenotypic variation of nystagmus occurs in families with FRMD7 mutations. While FRMD7 mutations may be found in some cases of X-linked congenital idiopathic nystagmus, the diagnostic yield is low. X-inactivation assays are unhelpful as a test for carrier status for this disease. PMID- 17846368 TI - Macular degeneration: risk factors for progression. PMID- 17846370 TI - Illusion of perception. PMID- 17846369 TI - Investigating the burden of wet macular degeneration. PMID- 17846371 TI - Predictive value of multiple genetic testing for age-related macular degeneration. PMID- 17846372 TI - Medical education 2007. PMID- 17846373 TI - Impact of the cryotherapy for retinopathy of prematurity randomized clinical trial. PMID- 17846374 TI - Evaluating the Cryotherapy for Retinopathy of Prematurity Study (CRYO-ROP). PMID- 17846375 TI - Viscocanalostomy for refractory glaucoma secondary to intravitreal triamcinolone acetonide injection. PMID- 17846376 TI - Endogenous Scedosporium apiospermum endophthalmitis. PMID- 17846377 TI - Primary orbital peripheral T-cell lymphoma: histologic, immunophenotypic, and genotypic features. PMID- 17846378 TI - Postoperative vancomycin-resistant Enterococcus faecium endophthalmitis. PMID- 17846379 TI - Improved binocularity after laser in situ keratomileusis. PMID- 17846380 TI - Metastatic cutaneous melanoma involving the retina and vitreous. PMID- 17846381 TI - Choroidal neovascularization from a presumed subretinal nematode. PMID- 17846382 TI - Glial cell proliferation under the internal limiting membrane in a patient with cellophane maculopathy. PMID- 17846383 TI - Hemorrhagic posterior vitreous detachment without intraretinal hemorrhage in a shaken infant. PMID- 17846384 TI - Hydroxychloroquine dosages should be calculated using lean body mass. PMID- 17846386 TI - Difficulties in mutation screening of the plasminogen (PLG) gene in patients with ligneous conjunctivitis and severe hypoplasminogenemia. PMID- 17846388 TI - Can vitamin D reduce total mortality? PMID- 17846389 TI - Medical decision making for patients without surrogates. AB - Patients who lose decision-making capacity and lack advance directives and next of kin present a quandary for physicians. Current mechanisms for making treatment decisions for these patients rely on decision makers, such as courts, public guardians, committees, and physicians, who typically do not have sufficient knowledge to predict the patients' preferences. Thus, these mechanisms likely yield decisions that are inconsistent with patients' treatment preferences in many cases. A population-based treatment indicator is a computer-based tool that predicts which treatment a given patient would prefer based on the treatment preferences of similar patients in similar situations. A recent analysis suggests that a population-based treatment indicator could predict patient preferences as accurately as patient-appointed surrogates and next of kin. This analysis suggests that a population-based treatment indicator may provide a mechanism to respect the treatment preferences of patients without surrogates and ensure that their treatment preferences are respected as much as the preferences of patients who have surrogates. Collection of data on patients' treatment preferences, especially those without surrogates, incorporation of these data into a treatment indicator, and exploration of ways to implement this approach for patients without surrogates are called for. PMID- 17846390 TI - Association of overweight with increased risk of coronary heart disease partly independent of blood pressure and cholesterol levels: a meta-analysis of 21 cohort studies including more than 300 000 persons. AB - BACKGROUND: The extent to which moderate overweight (body mass index [BMI], 25.0 29.9 [calculated as weight in kilograms divided by height in meters squared]) and obesity (BMI, >/= 30.0) are associated with increased risk of coronary heart disease (CHD) through adverse effects on blood pressure and cholesterol levels is unclear, as is the risk of CHD that remains after these mediating effects are considered. METHODS: Relative risks (RRs) of CHD associated with moderate overweight and obesity with and without adjustment for blood pressure and cholesterol concentrations were calculated by the members of a collaboration of prospective cohort studies of healthy, mainly white persons and pooled by means of random-effects models (RRs for categories of BMI in 14 cohorts and for continuous BMI in 21 cohorts; total N = 302 296). RESULTS: A total of 18 000 CHD events occurred during follow-up. The age-, sex-, physical activity-, and smoking adjusted RRs (95% confidence intervals) for moderate overweight and obesity compared with normal weight were 1.32 (1.24-1.40) and 1.81 (1.56-2.10), respectively. Additional adjustment for blood pressure and cholesterol levels reduced the RR to 1.17 (1.11-1.23) for moderate overweight and to 1.49 (1.32 1.67) for obesity. The RR associated with a 5-unit BMI increment was 1.29 (1.22 1.35) before and 1.16 (1.11-1.21) after adjustment for blood pressure and cholesterol levels. CONCLUSIONS: Adverse effects of overweight on blood pressure and cholesterol levels could account for about 45% of the increased risk of CHD. Even for moderate overweight, there is a significant increased risk of CHD independent of these traditional risk factors, although confounding (eg, by dietary factors) cannot be completely ruled out. PMID- 17846391 TI - Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. AB - BACKGROUND: Ecological and observational studies suggest that low vitamin D status could be associated with higher mortality from life-threatening conditions including cancer, cardiovascular disease, and diabetes mellitus that account for 60% to 70% of total mortality in high-income countries. We examined the risk of dying from any cause in subjects who participated in randomized trials testing the impact of vitamin D supplementation (ergocalciferol [vitamin D(2)] or cholecalciferol [vitamin D(3)]) on any health condition. METHODS: The literature up to November 2006 was searched without language restriction using the following databases: PubMed, ISI Web of Science (Science Citation Index Expanded), EMBASE, and the Cochrane Library. RESULTS: We identified 18 independent randomized controlled trials, including 57 311 participants. A total of 4777 deaths from any cause occurred during a trial size-adjusted mean of 5.7 years. Daily doses of vitamin D supplements varied from 300 to 2000 IU. The trial size-adjusted mean daily vitamin D dose was 528 IU. In 9 trials, there was a 1.4- to 5.2-fold difference in serum 25-hydroxyvitamin D between the intervention and control groups. The summary relative risk for mortality from any cause was 0.93 (95% confidence interval, 0.87-0.99). There was neither indication for heterogeneity nor indication for publication biases. The summary relative risk did not change according to the addition of calcium supplements in the intervention. CONCLUSIONS: Intake of ordinary doses of vitamin D supplements seems to be associated with decreases in total mortality rates. The relationship between baseline vitamin D status, dose of vitamin D supplements, and total mortality rates remains to be investigated. Population-based, placebo-controlled randomized trials with total mortality as the main end point should be organized for confirming these findings. PMID- 17846392 TI - Improving sleep hygiene of medical interns: can the sleep, alertness, and fatigue education in residency program help? AB - BACKGROUND: Because of concerns regarding sleep deprivation, the Accreditation Council for Graduate Medical Education limits duty hours and endorses education regarding sleep loss for residents. We assessed the effectiveness of a 60- to 90 minute lecture, the Sleep, Alertness, and Fatigue Education in Residency (SAFER) program, on sleep loss and recovery sleep in residents adhering to Accreditation Council for Graduate Medical Education duty hours. METHODS: From July 1, 2003, through June 24, 2005, interns from the inpatient medicine service at the University of Chicago were asked to wear wristwatch activity monitors. In March 2005, interns received the SAFER program intervention. We used fixed-effects linear regression to estimate within-subject mean sleep per call day (on-call, precall, postcall, and second-day postcall sleep). These estimates were compared with recommended minimum levels of preventive (7 hours of precall) and recovery (16 hours during the 2 days after call) sleep in healthy populations using 2 tailed t tests. These analyses were repeated to test the effect of the SAFER program. RESULTS: Fifty-eight of 81 interns (72%) participated for 147 intern months (63%). Interns on call slept an average of 2.84 hours (95% confidence interval, 2.75-2.93 hours). Interns obtained less than recommended amounts of recovery sleep (14.06 hours [95% confidence interval, 13.84-14.28 hours]; P < .001). Intern preventive sleep was also less than recommended (6.47 hours [95% confidence interval, 6.39-6.56 hours]; P < .001). Interns attempted to compensate for their acute sleep loss; for each hour of on-call sleep loss, they received 18 minutes (95% confidence interval, 7-30 minutes) more recovery sleep (P = .003). The SAFER program had no significant beneficial effect on intern sleep. CONCLUSIONS: Under the current duty-hour regulations of the Accreditation Council for Graduate Medical Education, residents continue to be sleep deprived. The SAFER program has no impact on resident precall or postcall sleep. PMID- 17846393 TI - White matter lesions and the risk of incident hip fracture in older persons: results from the progetto veneto anziani study. AB - BACKGROUND: White matter lesions (WMLs) are associated with hypertension, an increased risk of falling, and impaired physical and cognitive performance that may affect the mechanical effect of falls. METHODS: We hypothesized that WMLs are a risk factor for hip fracture (HF). We studied a sample of 820 community dwelling Italian persons 65 years and older from the cohort of the Progetto Veneto Anziani Study who underwent brain magnetic resonance imaging at baseline. Subjects were classified as having no lesions, focal lesions, or diffuse WMLs. RESULTS: Compared with those with no lesions, participants with diffuse WMLs were older, reported more falls, and had worse physical and cognitive performance, all factors implicated in the causal pathway to HF. During 9 years of follow-up, 51 HFs occurred. Hip fracture risk associated with diffuse WMLs markedly differed between participants younger than 80 years vs those 80 years and older. After adjustment among participants younger than 80 years, diffuse WMLs compared with no lesions were associated with a 2.7-fold (95% confidence interval, 1.1-7.1) increase in the risk of HF. Focal lesions were not statistically significantly associated with an increased risk of HF in the same age group (hazard ratio, 2.0; 95% confidence interval, 0.6-7.6). No associations between diffuse WMLs, focal lesions, and HF were evident among participants 80 years and older, possibly because of the limited sample size. CONCLUSIONS: White matter lesions represent an independent risk factor for HF in persons younger than 80 years. Older persons with diffuse WMLs should be considered candidates for multifactorial interventions aimed at reducing the risk of falling and fractures. PMID- 17846394 TI - Serious adverse drug events reported to the Food and Drug Administration, 1998 2005. AB - BACKGROUND: The US Food and Drug Administration has operated the Adverse Event Reporting System since 1998. It collects all voluntary reports of adverse drug events submitted directly to the agency or through drug manufacturers. METHODS: Using extracts published for research use, we analyzed all serious adverse drug events and medication errors in the United States reported to the Food and Drug Administration from 1998 through 2005. RESULTS: From 1998 through 2005, reported serious adverse drug events increased 2.6-fold from 34 966 to 89 842, and fatal adverse drug events increased 2.7-fold from 5519 to 15 107. Reported serious events increased 4 times faster than the total number of outpatient prescriptions during the period. In a subset of drugs with 500 or more cases reported in any year, drugs related to safety withdrawals accounted for 26% of reported events in that group in 1999, declining to less than 1% in 2005. For 13 new biotechnology products, reported serious events grew 15.8-fold, from 580 reported in 1998 to 9181 in 2005. The increase was influenced by relatively few drugs: 298 of the 1489 drugs identified (20%) accounted for 407 394 of the 467 809 events (87%). CONCLUSIONS: These data show a marked increase in reported deaths and serious injuries associated with drug therapy over the study period. The results highlight the importance of this public health problem and illustrate the need for improved systems to manage the risks of prescription drugs. PMID- 17846395 TI - The variability and quality of medication container labels. AB - BACKGROUND: Medication errors occur frequently, and poor medication labeling is cited as a potential cause. We assessed the format, content, and variability of prescription drug container labels dispensed in the community. METHODS: Identically written prescriptions for 4 commonly used medications (atorvastatin calcium [Lipitor], alendronate sodium [Fosamax], trimethoprim-sulfamethoxazole [Bactrim], and ibuprofen) were filled in 6 pharmacies (the 2 largest chains, 2 grocery stores, and 2 independent pharmacies) in 4 cities (Boston, Chicago, Los Angeles, and Austin [Texas]). Characteristics of the format and content of the main container label and auxiliary stickers were evaluated. Labels were coded independently by 2 abstractors, and differences were reconciled by consensus. RESULTS: We evaluated 85 labels after excluding 11 ibuprofen prescriptions that were filled with over-the-counter containers that lacked labels printed at the pharmacy. The pharmacy name or logo was the most prominent item on 71 (84%) of the labels, with a mean font size of 13.6 point. Font sizes were smaller for medication instructions (9.3 point), medication name (8.9 point), and warning and instruction stickers (6.5 point). Color, boldfacing, and highlighting were most often used to identify the pharmacy and items most useful to pharmacists. While the content of the main label was generally consistent, there was substantial variability in the content of instruction and warning stickers from different pharmacies, and independent pharmacies were less likely to use such stickers (P < .001). None of the ibuprofen containers were delivered with Food and Drug Administration-approved medication guides, as required by law. CONCLUSIONS: The format of most container labels emphasizes pharmacy characteristics and items frequently used by pharmacists rather than use instructions or medication warnings. The content of warning and instruction stickers is highly variable depending on the pharmacy selected. PMID- 17846396 TI - Increasing use of single and combination medical therapy in patients hospitalized for acute myocardial infarction in the 21st century: a multinational perspective. AB - BACKGROUND: Current practice guidelines recommend the routine use of several effective cardiac medications in hospital survivors of acute myocardial infarction (AMI). METHODS: We explored a recent 5-year (2000-2005) trend in hospital use of aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, lipid-lowering agents, and combinations thereof, in 26 413 adult men and women without contraindications to any of these therapies discharged after AMI from hospitals located in 14 countries that were included in the Global Registry of Acute Coronary Events. RESULTS: Relatively steady increases in the use of ACE inhibitors, beta-blockers, and statin therapy were observed over time, with particularly marked increases in the use of lipid-lowering therapy (from 45% in 2000 to 85% in 2005). Aspirin use remained high (by approximately 95% of patients after AMI) during all periods examined. The percentage of hospital survivors treated with all 4 cardiac medications increased from 23% in 2000 to 58% during 2005. Advancing age (>/= 65 years), female sex, medical history of heart failure or stroke, and development of atrial fibrillation during hospitalization were associated with underuse of combination medical therapy. Relatively similar factors were associated with the underuse of combination medical therapy in patients with ST-segment elevation AMI and non-ST-segment elevation AMI. CONCLUSIONS: Our results suggest encouraging increases over time in the use of combination medical therapy in patients hospitalized with AMI without contraindications to these medications. Educational efforts designed to increase the use of these therapies, as well as efforts to simplify medication regimens and enhance rates of adherence, remain warranted. PMID- 17846397 TI - Physical activity counseling and prescription among canadian primary care physicians. AB - BACKGROUND: Primary care physicians are ideally positioned to affect a large population at risk for epidemics of sedentary lifestyle; however, it is unclear what type of counseling they provide. METHODS: A questionnaire was used to obtain information on primary care physicians' behaviors with respect to counseling and prescribing physical activity, physician demographics, and practice characteristics. Registered primary care physicians in Canada were contacted in all 10 provinces and 2 territories. RESULTS: Of 27 980 primary care physicians, 14 319 returned usable questionnaires and 13 166 were eligible for study participation (response rate, 51.2%). Respondents were predominantly male (61.1%), practiced in private office/clinic settings (73.4%), and had graduated from medical school more than 22 years earlier. Eighty-five percent of respondents reported asking patients about their physical activity levels, whereas only 26.2% assessed patient fitness as part of a physical examination or through a fitness test and only 10.9% referred patients to others for fitness assessment or appraisal. Most physicians (69.8%) reported using verbal counseling to promote physical activity, whereas only 15.8% used written prescriptions for a physical activity promotion program. Male and female physicians responded differently. Men more frequently assessed fitness than did women, whereas women more frequently asked and provided verbal and written directions. CONCLUSIONS: This large sample of Canadian primary care physicians regularly asked patients about physical activity levels and advised them using verbal counseling. Few respondents provided written prescriptions, performed fitness assessments, or referred patients. These results suggest possible opportunities to improve physicians' counseling and prescription efforts. PMID- 17846398 TI - Emergence of HIV-1 drug resistance in previously untreated patients initiating combination antiretroviral treatment: a comparison of different regimen types. AB - BACKGROUND: Standard first-line combination antiretroviral treatment (cART) against human immunodeficiency virus 1 (HIV-1) contains either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r). Differences between these regimen types in the extent of the emergence of drug resistance on virological failure and the implications for further treatment options have rarely been assessed. METHODS: We investigated virological outcomes in patients from the Swiss HIV Cohort Study initiating cART between January 1, 1999, and December 31, 2005, with an unboosted PI, a PI/r, or an NNRTI and compared genotypic drug resistance patterns among these groups at treatment failure. RESULTS: A total of 489 patients started cART with a PI, 518 with a PI/r, and 805 with an NNRTI. A total of 177 virological failures were observed (108 [22%] PI failures, 24 [5%] PI/r failures, and 45 [6%] NNRTI failures). The failure rate was highest in the PI group (10.3 per 100 person-years; 95% confidence interval [CI], 8.5-12.4). No difference was seen between patients taking a PI/r (2.7; 95% CI, 1.8-4.0) and those taking an NNRTI (2.4; 95% CI, 1.8 3.3). Genotypic test results were available for 142 (80%) of the patients with a virological treatment failure. Resistance mutations were found in 84% (95% CI, 75%-92%) of patients taking a PI, 30% (95% CI, 12%-54%) of patients taking a PI/r, and 66% (95% CI, 49%-80%) of patients taking an NNRTI (P < .001). Multidrug resistance occurred almost exclusively as resistance against lamivudine emtricitabine and the group-specific third drug and was observed in 17% (95% CI, 9%-26%) of patients taking a PI, 10% (95% CI, 0.1%-32%) of patients taking a PI/r, and 50% (95% CI, 33%-67%) of patients taking an NNRTI (P < .001). CONCLUSIONS: Regimens that contained a PI/r or an NNRTI exhibited similar potency as first-line regimens. However, the use of a PI/r led to less resistance in case of virological failure, preserving more drug options for the future. PMID- 17846399 TI - A double-blind, placebo-controlled, randomized trial of bupropion for smoking cessation in primary care. AB - BACKGROUND: Studies undertaken in academic settings have shown that bupropion hydrochloride can double the odds of smoking cessation compared with placebo. To assess whether these results are applicable in primary care, we launched a double blind, placebo-controlled, randomized trial to be conducted by general practitioners. METHODS: We assigned 593 healthy smokers to receive bupropion hydrochloride, 150 mg twice a day, or placebo daily for 7 weeks (hereinafter, bupropion group [n = 400] and placebo group [n = 193], respectively). After the baseline visit, 4 clinical visits and 3 telephone calls were scheduled over the 1 year period. The primary end points were biochemically confirmed continuous abstinence at week 7 and at week 52. RESULTS: Seventy-one Italian general practitioners enrolled participants from April 2004 to May 2005. Of the bupropion group, 41.0% were continuously abstinent from week 4 to week 7 compared with 22.3% of the placebo group (multivariate odds ratio, 2.37; 95% confidence interval, 1.60-3.53). The continuous abstinence rates from week 4 to week 52 were 25% in the bupropion group and 14% in the placebo group (odds ratio, 2.11; 95% confidence interval, 1.32-3.39). The mean weight gain was similar in both groups and among long-term abstainers was 3 kg in women and 4 kg in men. More participants in the bupropion group experienced an adverse event than those in the placebo group, but the percentage who discontinued use of the study medication was similar. CONCLUSIONS: Bupropion more than doubled the odds of continuous abstinence from smoking. The adherence of general practitioners and participants to the protocol was excellent, making our findings robust and easy to generalize to the context of primary care. PMID- 17846400 TI - Self-reported medication adherence and cardiovascular events in patients with stable coronary heart disease: the heart and soul study. AB - BACKGROUND: Nonadherence to physician treatment recommendations is an increasingly recognized cause of adverse outcomes and increased health care costs, particularly among patients with cardiovascular disease. Whether patient self-report can provide an accurate assessment of medication adherence in outpatients with stable coronary heart disease is unknown. METHODS: We prospectively evaluated the risk of cardiovascular events associated with self reported medication nonadherence in 1015 outpatients with established coronary heart disease from the Heart and Soul Study. We asked participants a single question: "In the past month, how often did you take your medications as the doctor prescribed?" Nonadherence was defined as taking medications as prescribed 75% of the time or less. Cardiovascular events (coronary heart disease death, myocardial infarction, or stroke) were identified by review of medical records during 3.9 years of follow-up. We used Cox proportional hazards analysis to determine the risk of adverse cardiovascular events associated with self-reported medication nonadherence. RESULTS: Of the 1015 participants, 83 (8.2%) reported nonadherence to their medications, and 146 (14.4%) developed cardiovascular events. Nonadherent participants were more likely than adherent participants to develop cardiovascular events during 3.9 years of follow-up (22.9% vs 13.8%, P = .03). Self-reported nonadherence remained independently predictive of adverse cardiovascular events after adjusting for baseline cardiac disease severity, traditional risk factors, and depressive symptoms (hazards ratio, 2.3; 95% confidence interval, 1.3-4.3; P = .006). CONCLUSIONS: In outpatients with stable coronary heart disease, self-reported medication nonadherence is associated with a greater than 2-fold increased rate of subsequent cardiovascular events. A single question about medication adherence may be a simple and effective method to identify patients at higher risk for adverse cardiovascular events. PMID- 17846401 TI - Infliximab with low-dose methotrexate for prevention of postsurgical recurrence of ileocolonic Crohn disease. PMID- 17846402 TI - Prisoners (should) count. PMID- 17846403 TI - Chronic venous disease and injection drug use. PMID- 17846404 TI - Isolated CNS Whipple disease with a variant of oculofacial-skeletal myorhythmia (OFSM). PMID- 17846406 TI - Should surgical menopausal women be treated with estrogens to decrease the risk of dementia? PMID- 17846407 TI - Pass the grain; spare the brain. PMID- 17846408 TI - Mediterranean diet and Alzheimer disease mortality. AB - BACKGROUND: We previously reported that the Mediterranean diet (MeDi) is related to lower risk for Alzheimer disease (AD). Whether MeDi is associated with subsequent AD course and outcomes has not been investigated. OBJECTIVES: To examine the association between MeDi and mortality in patients with AD. METHODS: A total of 192 community-based individuals in New York who were diagnosed with AD were prospectively followed every 1.5 years. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of mortality in Cox models that were adjusted for period of recruitment, age, gender, ethnicity, education, APOE genotype, caloric intake, smoking, and body mass index. RESULTS: Eighty-five patients with AD (44%) died during the course of 4.4 (+/-3.6, 0.2 to 13.6) years of follow-up. In unadjusted models, higher adherence to MeDi was associated with lower mortality risk (for each additional MeDi point hazard ratio 0.79; 95% CI 0.69 to 0.91; p = 0.001). This result remained significant after controlling for all covariates (0.76; 0.65 to 0.89; p = 0.001). In adjusted models, as compared with AD patients at the lowest MeDi adherence tertile, those at the middle tertile had lower mortality risk (0.65; 0.38 to 1.09; 1.33 years' longer survival), whereas subjects at the highest tertile had an even lower risk (0.27; 0.10 to 0.69; 3.91 years' longer survival; p for trend = 0.003). CONCLUSION: Adherence to the Mediterranean diet (MeDi) may affect not only risk for Alzheimer disease (AD) but also subsequent disease course: Higher adherence to the MeDi is associated with lower mortality in AD. The gradual reduction in mortality risk for higher MeDi adherence tertiles suggests a possible dose-response effect. PMID- 17846409 TI - Peripheral insulin and brain structure in early Alzheimer disease. AB - OBJECTIVE: Accumulating evidence suggests insulin and insulin signaling may be involved in the pathophysiology of Alzheimer disease (AD). The relationship between insulin-mediated glucoregulation and brain structure has not been assessed in individuals with AD. METHODS: Nondemented (Clinical Dementia Rating [CDR] 0, n = 31) and early stage AD (CDR 0.5 and 1, n = 31) participants aged 65 years and older had brain MRI to determine whole brain and hippocampal volume and 3-hour IV glucose tolerance tests to determine glucose and insulin area under the curve (AUC). Linear regression models were used to assess the relationship of insulin and glucose with brain volume, cognition, and dementia severity. RESULTS: In early AD, insulin and glucose AUCs were related to whole brain (insulin beta = 0.66, p < 0.001; glucose beta = 0.45, p < 0.01) and hippocampal volume (insulin beta = 0.42, p < 0.05; glucose beta = 0.46, p < 0.05). These relationships were independent of age, sex, body mass index, body fat, cardiorespiratory fitness, physical activity, cholesterol, and triglycerides. Insulin AUC, but not glucose, was associated with cognitive performance in early AD (beta = 0.40, p = 0.04). Insulin AUC was associated with dementia severity (Pearson r = -0.40, p = 0.03). Glucose and insulin were not related to brain volume or cognitive performance in nondemented individuals. CONCLUSIONS: Increased peripheral insulin is associated with reduced Alzheimer disease (AD)-related brain atrophy, cognitive dysfunction, and dementia severity, suggesting that insulin signaling may play a role in the pathophysiology of AD. PMID- 17846410 TI - Attentional distractibility by optokinetic stimulation in Alzheimer disease. AB - OBJECTIVE: Unilateral temporoparietal injury may result in an attentional deficit for stimuli presented in contralesional space. Thus, bilateral temporoparietal degeneration associated with Alzheimer disease (AD) might result in a bilateral attentional disturbance. Tests for hemispatial neglect, however, primarily assess spatial attentional asymmetries, and a bilateral attentional disorder might not be detected with these tests. The goal of this study was to learn whether optokinetic stimulation (OKS) would perturb the balanced attentional deficits of AD patients and alter their spatial allocation of attention. METHODS: In Experiment I, 10 AD patients with bilateral temporoparietal glucose hypometabolism on PET and 10 controls bisected lines in two conditions: stationary solid lines superimposed on a moving background and "striped lines" where the whole line was stationary but the stripes within the line moved. The background OKS or the stripes within the line moved leftward or rightward or were stationary. In Experiment II, to investigate whether the influence of background movements would increase with AD severity, we conducted a similar experiment in 56 patients with various stages of AD. RESULTS: In Experiment I, the line bisection errors (LBEs) of AD subjects, but not of the controls, were markedly influenced by both background and within line stripe motions, deviations occurring in the same direction of movement. In Experiment II, LBEs also occurred in the same direction as background movement and increased with dementia severity. CONCLUSIONS: These results demonstrate that patients with Alzheimer disease are spatially distracted by moving stimuli. PMID- 17846411 TI - Dissociation of neglect subtypes with transcranial magnetic stimulation. AB - OBJECTIVE: To identify two forms of hemispatial neglect, attentional and intentional, in healthy volunteers using frontal and parietal repetitive transcranial magnetic stimulation (rTMS). METHODS: Ten healthy volunteers performed line bisection tasks while viewing stimuli on closed circuit TV. Direct view of the exploring hand and the target was precluded and the TV monitor guided performance. In the normal condition, the direction of hand movement on the table (workspace) was congruent with that on the monitor, and in the reversed condition, the lateral movement in the workspace occurred in the opposite direction on the monitor. The line bisections were performed in three conditions: without rTMS (control), with right frontal rTMS, and with right parietal rTMS. RESULTS: In the normal condition, both right frontal and right parietal rTMS caused a significant rightward deviation (left hemispatial neglect). In the reversed condition, right frontal rTMS continued to cause rightward deviation in the workspace corresponding to leftward bias on the monitor, whereas right parietal rTMS caused leftward deviation in the workspace, corresponding to rightward bias on the monitor. CONCLUSIONS: Right frontal repetitive transcranial magnetic stimulation causes motor-intentional neglect, whereas right parietal repetitive transcranial magnetic stimulation causes sensory-attentional neglect. Alternatively, these findings can also be explained based on a dichotomy related to an egocentric-oriented system. PMID- 17846412 TI - Structural and functional MRIs disclose cerebellar pathologies in idiopathic downbeat nystagmus. AB - BACKGROUND: Neurologic disorders in which the etiology and pathogenesis are not yet understood are termed idiopathic. Downbeat nystagmus (DBN) is a frequent eye movement disorder that clinically manifests with oscillopsia and postural instability. Forty percent of patients with DBN are classified as having idiopathic DBN, because no underlying pathology can be demonstrated by conventional MRI or laboratory tests. METHODS: We evaluated gray matter brain volumes of 11 patients with idiopathic DBN and compared them to those of healthy controls using voxel-based morphometry. In a second, functional MRI experiment, patients and controls performed downward smooth pursuit eye movements (DOWN), which were then compared with straight-ahead fixation of a stationary target (MID). RESULTS: Small areas of localized gray matter atrophy were detected in the lateral cerebellar hemispheres (lobule VI) and ocular motor vermis of patients with idiopathic DBN, but not in the flocculus and paraflocculus. The functional imaging data, however, revealed reduced activation in the parafloccular lobule and in the ponto-medullary brainstem of the patients when they performed smooth pursuit eye movements downwards. CONCLUSIONS: The applied specialized imaging and data analysis techniques disclosed pathologies in an idiopathic eye movement disorder. The focal atrophy found in the vermal and lateral cerebellar regions in downbeat nystagmus (DBN) may lead to deficits in smooth pursuit eye movement initiation, which in turn causes hypofunction of the parafloccular lobe, associated with DBN. Our data are in line with experiments in primates showing that ablation of the floccular and parafloccular lobes disrupts smooth pursuit and causes DBN. PMID- 17846413 TI - Primary systemic amyloidosis with ischemic stroke as a presenting complication. AB - BACKGROUND: Amyloidosis is an uncommon disorder that ultimately leads to fatal multiorgan failure. Ischemic strokes have been sporadically described but are not well characterized. The purpose of this study was to review the pathophysiologic relationship between primary systemic amyloidosis and ischemic stroke, and to determine how often stroke is the first defining manifestation. METHODS: Retrospective study of 49 patients with confirmed primary amyloidosis and ischemic stroke. All included patients had biopsy proven amyloidosis. RESULTS: Forty patients were included in the study. Ischemic strokes occurred in 13 patients (32.5%) as the initial presentation of amyloidosis. Patients with initial stroke presentation had the worst outcome, with average survival of 6.9 months after established diagnosis with amyloidosis; strokes developed 9.6 months before diagnosis with primary amyloidosis. Thirty-seven percent experienced recurrent ischemic stroke. The majority (70%) of patients had cardioembolic infarctions. CONCLUSIONS: Ischemic stroke is an underappreciated complication of primary amyloidosis. In the absence of obvious clinical and cardiogenic manifestations, primary amyloidosis should be considered when echocardiography demonstrates thickening of the valves, restrictive pattern, and increased echogenicity. Ischemic strokes as an initial presentation of primary amyloidosis carries a worse prognosis. PMID- 17846414 TI - Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease. AB - OBJECTIVE: Dysfunction of mitochondrial DNA polymerase gamma (POLG) has been recently recognized as an important cause of inherited neurodegenerative diseases. We have reported dominant and recessive inheritance of parkinsonism, mitochondrial myopathy, and premature amenorrhea in five ethnically distinct families with POLG1 mutations. This prompted us to carry out a detailed analysis of the coding region and intron-exon boundaries of POLG1 in Finnish patients with idiopathic sporadic Parkinson disease (PD) and in nonparkinsonian controls. METHODS: The coding region of POLG1 was analyzed in 140 Finnish patients with PD and their 127 spouses as age- and ethnically matched controls. Further, we analyzed the intragenic CAG-repeat region of POLG1 in 126 additional patients with nonparkinsonian neurologic disorders and in 516 Finnish population controls. RESULTS: We found clustering of rare variants of the POLG1 CAG-repeat, encoding a polyglutamine tract, in Finnish patients with idiopathic PD as compared to their spouses (p = 0.003; OR 3.01, 95% CI 1.35 to 6.71), population controls (p = 0.001; OR 2.45, 95% CI 1.45 to 4.14), and patients with nonparkinsonian neurologic disorders (p = 0.05, OR 1.98, 95% CI 0.97 to 4.05). We found several amino acid substitutions, none of them associating with PD. These included a previously parkinsonism-associated POLG variant Y831C, found in one patient with PD, but also in five controls, suggesting that it is a neutral amino acid polymorphism. CONCLUSIONS: Our results suggest that POLG polyglutamine tract variants should be considered as a predisposing genetic factor in idiopathic sporadic Parkinson disease. PMID- 17846415 TI - Eye movement abnormalities in spinocerebellar ataxia type 17 (SCA17). AB - BACKGROUND: Spinocerebellar ataxia type 17 (SCA17) is associated with an expansion of CAG/CAA trinucleotide repeats in the gene encoding the TATA-binding protein. In this quantitative characterization of eye movements in SCA17 mutation carriers, we investigated whether eye movement abnormalities originate from multiple lesion sites as suggested by their phenotypic heterogeneity. METHODS: Eye movements (saccades, smooth pursuit) of 15 SCA17 mutation carriers (mean age 36.9 years, range 20 to 54 years; mean disease duration 7.3 years, range 0 to 20 years; 2 clinically unaffected, 13 affected) were compared with 15 age-matched control subjects using the video-based two-dimensional EYELINK II system. RESULTS: Smooth pursuit initiation (step-ramp paradigm) and maintenance were strongly impaired, i.e., pursuit latency was increased and acceleration decreased, whereas latency and position error of the first catch-up saccade were normal. Visually guided saccades were hypometric but had normal velocities. Gaze evoked nystagmus was found in one-third of the mutation carriers, including downbeat and rebound nystagmus. There was a pathologic increase in error rates of antisaccades (52%) and memory-guided saccades (42%). Oculomotor disorders were not correlated with repeat length. Smooth pursuit impairment and saccadic disorders increased with disease duration. CONCLUSIONS: Several oculomotor deficits of spinocerebellar ataxia type 17 (SCA17) mutation carriers are compatible with cerebellar degeneration. This is consistent with histopathologic and imaging (morphometric) data. In contrast, increased error rates in antisaccades and memory-guided saccades point to a deficient frontal inhibition of reflexive movements, which is probably best explained by cortical dysfunction and may be related to other phenotypic SCA17 signs, e.g., dementia and parkinsonism. PMID- 17846416 TI - Head or neck injury increases the risk of chronic daily headache: a population based study. AB - OBJECTIVE: To evaluate the extent to which head and neck injury (HANI) contributes to chronic daily headache (CDH). BACKGROUND: In prospective studies, head injury is associated with headache (HA) that remains a problem at 12 to 24 months post-head injury in 20 to 30% of patients. Of these, up to 30 to 50% manifest CDH. The degree to which head injury contributes to CDH has not been evaluated in a non-clinical population. We evaluate the relationship between lifetime occurrence of HANI and CDH in a randomly chosen population sample. METHODS: Study participants are from the Frequent Headache Epidemiology Study. Cases with CDH (> or =180 HA/year) and a comparison group with episodic headache (EH, 2 to 102 HA/year) were identified from the general population. Subjects were asked about lifetime occurrence of HANI. HANI were further classified as potentially precipitating injuries (PPI) if they occurred within 2 years of CDH onset for cases or in an equivalent 2-year period for EH controls. RESULTS: Lifetime occurrence of HANI was more frequent in cases than controls for men (adjusted OR = 3.1 [1.3 to 7.2]), women (OR = 1.5 [0.97 to 2.3]), and overall (OR = 1.7 [1.1 to 2.4]). The attributable risk was 15% (36% men, 11% women). Results were similar for PPI. The odds of CDH increased with the number of lifetime HANI in all groups (p < 0.05 trend). CONCLUSIONS: Results suggest that head and neck injury (HANI) accounts for approximately 15% of chronic daily headache (CDH) cases in this non-clinical population. The relationship between HANI and CDH was not limited to injuries proximate to CDH onset. The lifetime risk of CDH increases with increasing number of HANI. PMID- 17846417 TI - Salvage whole brain radiotherapy for recurrent or refractory primary CNS lymphoma. AB - BACKGROUND: High-dose methotrexate (MTX) and whole brain radiation therapy (WBRT) prolong survival in primary CNS lymphoma (PCNSL) patients but have been associated with delayed neurotoxicity. Consequently, patients are often treated with chemotherapy alone, and WBRT is deferred until relapse. METHODS: We performed a retrospective study to evaluate the safety and efficacy of salvage WBRT. Radiographic response, survival, and late neurotoxicity were assessed as the main endpoints. RESULTS: Forty-eight patients received salvage WBRT for PCNSL progression or recurrence. After WBRT, 58% achieved a complete radiographic response, 21% achieved a partial response, 6% had stable disease, and 15% progressed. The median survival from initiation of WBRT was 16 months, and 54% were alive 1 year after WBRT. The median time to PCNSL progression was 10 months; 15 patients (31%) had no subsequent disease recurrence after WBRT. Age younger than 60 years and complete response to WBRT were associated with better outcome. Treatment-related neurotoxicity was observed in 22% of patients. Patients older than 60 years and those treated less than 6 months from MTX therapy were at increased risk for development of neurotoxicity. CONCLUSIONS: Salvage whole brain radiation therapy (WBRT) is effective for recurrent and refractory primary CNS lymphoma. Reserving WBRT until tumor recurrence is a reasonable strategy to minimize or delay the risk of treatment-related neurotoxicity. PMID- 17846418 TI - A 75-year-old man with cognitive impairment and gait changes. PMID- 17846419 TI - Assessment: use of epidural steroid injections to treat radicular lumbosacral pain: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. PMID- 17846420 TI - Assessment: use of epidural steroid injections to treat radicular lumbosacral pain: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. PMID- 17846421 TI - AAN Board of Directors recommends formation of a companion association to establish a political action committee. PMID- 17846422 TI - Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1. AB - The cornified layer is a compacted lattice of lipid-embedded corneocytes that provides an organism's barrier to the external environment. Cornification is the final differentiative step for epidermal keratinocytes and involves dramatic cell condensation before death. Using conditional gene deletion in mice, we identified the transcriptional repressor Blimp-1 (B lymphocyte-induced maturation protein-1) as an important regulator of keratinocyte transition from the granular to the cornified layer. More than 250 genes are misregulated in conditional knockout epidermis, including those encoding transcription factors, signal transduction components, proteinases, and enzymes involved in lipid metabolism. Steady-state mRNA and ChIP analyses of a subset of these genes provide evidence that nfat5, fos, prdm1, and dusp16 are novel direct targets of Blimp-1. Identifying nfat5 as a target of Blimp-1 repression indicates that cornification involves suppression of normal osmotic regulation in granular cells. Consistently, conditional knockout mice have delayed barrier formation as embryos, enlarged granular layer cells and corneocytes, and a morphologically abnormal cornified layer. These studies provide insight into cornification, identifying transcriptional regulatory circuitry and indicating the importance of blocking osmotic homeostasis. PMID- 17846423 TI - Effects of simian immunodeficiency virus on the circadian rhythms of body temperature and gross locomotor activity. AB - In monkeys infected with simian immunodeficiency virus (SIV), changes in body temperature and locomotor activity occur after the acute retroviral syndrome stage of the disease. However, alterations to the circadian rhythm of these factors in SIV-infected monkeys have not been reported. To determine whether the circadian rhythm of body temperature and locomotor activity are disrupted during SIV infection, we analyzed the temperature and activity patterns of SIV-infected monkeys through different stages of the disease, progressing to SIV encephalitis by using the cosinor model for circadian oscillation. We found that SIV infection resulted in significant impairments of the amplitude and mean of the circadian rhythm of body temperature and activity and in the acrophase of the circadian rhythm for temperature. These alterations were not related to changes observed in the acute febrile response induced after viral inoculation. In animals killed once marked circadian anomalies were evident, microglia infiltration and macrophage accumulation in the hypothalamus were observed. Together, these results clearly demonstrate that SIV infection compromises aspects of circadian regulation in monkeys, with important implications for physiological functions, including cognition, in HIV-infected individuals. PMID- 17846424 TI - Targeting the absence: homozygous DNA deletions as immutable signposts for cancer therapy. AB - Many cancers harbor homozygous DNA deletions (HDs). In contrast to other attributes of cancer cells, their HDs are immutable features that cannot change during tumor progression or therapy. I describe an approach, termed deletion specific targeting (DST), that employs HDs (not their effects on RNA/protein circuits, but deletions themselves) as the targets of cancer therapy. The DST strategy brings together both existing and new methodologies, including the ubiquitin fusion technique, the split-ubiquitin assay, zinc-finger DNA recognizing proteins and split restriction nucleases. The DST strategy also employs a feedback mechanism that receives input from a circuit operating as a Boolean OR gate and involves the activation of split nucleases, which destroy DST vector in normal (nontarget) cells. The logic of DST makes possible an incremental and essentially unlimited increase in the selectivity of therapy. If DST strategy can be implemented in a clinical setting, it may prove to be curative and substantially free of side effects. PMID- 17846425 TI - Envelope variation as a primary determinant of lentiviral vaccine efficacy. AB - Lentiviral envelope antigenic variation and associated immune evasion are believed to present major obstacles to effective vaccine development. Although this perception is widely assumed by the scientific community, there is, to date, no rigorous experimental data assessing the effect of increasing levels of lentiviral Env variation on vaccine efficacy. It is our working hypothesis that Env is, in fact, a primary determinant of vaccine effectiveness. We previously reported that a successful experimental attenuated equine infectious anemia virus vaccine, derived by mutation of the viral S2 accessory gene, provided 100% protection from disease after virulent virus challenge. Here, we sought to comprehensively test our hypothesis by challenging vaccinated animals with proviral strains of defined, increasing Env variation, using variant envelope SU genes that arose naturally during experimental infection of ponies with equine infectious anemia virus. The reference attenuated vaccine combined with these variant Env challenge strains facilitated evaluation of the protection conferred by ancestral immunogens, because the Env of the attenuated vaccine is a direct ancestor to the variant proviral strain Envs. The results demonstrated that ancestral Env proteins did not impart broad levels of protection against challenge. Furthermore, the results displayed a significant inverse linear correlation of Env divergence and protection from disease. This study demonstrates potential obstacles to the use of single isolate ancestral Env immunogens. Finally, these findings reveal that relatively minor Env variation can pose a substantial challenge to lentiviral vaccine immunity, even when attenuated vaccines are used that, to date, achieve the highest levels of vaccine protection. PMID- 17846427 TI - Energetics of water permeation through fullerene membrane. AB - Lipid bilayer membranes are important as fundamental structures in biology and possess characteristic water-permeability, stability, and mechanical properties. Water permeation through a lipid bilayer membrane occurs readily, and more readily at higher temperature, which is largely due to an enthalpy cost of the liquid-to-gas phase transition of water. A fullerene bilayer membrane formed by dissolution of a water-soluble fullerene, Ph(5)C(60)K, has now been shown to possess properties entirely different from those of the lipid membranes. The fullerene membrane is several orders of magnitude less permeable to water than a lipid membrane, and the permeability decreases at higher temperature. Water permeation is burdened by a very large entropy loss and may be favored slightly by an enthalpy gain, which is contrary to the energetics observed for the lipid membrane. We ascribe this energetics to favorable interactions of water molecules to the surface of the fullerene molecules as they pass through the clefts of the rigid fullerene bilayer. The findings provide possibilities of membrane design in science and technology. PMID- 17846426 TI - Tipin is required for stalled replication forks to resume DNA replication after removal of aphidicolin in Xenopus egg extracts. AB - Tipin and its interacting partner Tim1 (Timeless) form a complex at replication forks that plays an important role in the DNA damage checkpoint response. Here we identify Xenopus laevis Tipin as a substrate for cyclin E/cyclin-dependent kinases 2 that is phosphorylated in interphase and undergoes further phosphorylation upon entry into mitosis. During unperturbed DNA replication, the Tipin/Tim1 complex is bound to chromatin, and we were able to detect interactions between Tipin and the MCM helicase. Depletion of Tipin from Xenopus extracts did not significantly impair normal replication but substantially blocked the ability of stalled replication forks to recover after removal of a block imposed by aphidicolin. Tipin-depleted extracts also showed defects in the activation of Chk1 in response to aphidicolin, probably because of a failure to load the checkpoint mediator protein Claspin onto chromatin. PMID- 17846428 TI - High-density lipoprotein protects macrophages from oxidized low-density lipoprotein-induced apoptosis by promoting efflux of 7-ketocholesterol via ABCG1. AB - Oxidized sterols consumed in the diet or formed on low-density lipoprotein (LDL) are toxic to endothelial cells and macrophages and are thought to have a central role in promoting atherogenesis. The ATP-binding cassette transporter ABCG1 was recently shown to promote efflux of cholesterol from macrophages to high-denisty lipoprotein (HDL). We show that HDL protects macrophages from apoptosis induced by loading with free cholesterol or oxidized LDL. The protective effect of HDL was reduced in Abcg1(-/-) macrophages, especially after loading with oxidized LDL. Similarly, HDL exerted a protective effect against apoptosis induced by 7 ketocholesterol, the major oxysterol present in oxidized LDL and atherosclerotic lesions, in Abcg1(+/+), but not in Abcg1(-/-) macrophages. In transfected 293 cells, efflux of 7-ketocholesterol and related oxysterols was completely dependent on expression of ABCG1 and the presence of HDL in media. In contrast, ABCA1 and apoA-1 did not stimulate the efflux of 7-ketocholesterol into media. HDL stimulated the efflux of 7-ketocholesterol from Abcg1(+/+), but not from Abcg1(-/-) macrophages. In Abcg1(-/-) mice fed a high-cholesterol diet, plasma levels of 7-ketocholesterol were reduced, whereas their macrophages accumulated 7 ketocholesterol. These findings indicate a specific role for ABCG1 in promoting efflux of 7-ketocholesterol and related oxysterols from macrophages onto HDL and in protecting these cells from oxysterol-induced cytotoxicity. PMID- 17846429 TI - Interaction of signal-recognition particle 54 GTPase domain and signal recognition particle RNA in the free signal-recognition particle. AB - The signal-recognition particle (SRP) is a ubiquitous protein-RNA complex that targets proteins to cellular membranes for insertion or secretion. A key player in SRP-mediated protein targeting is the evolutionarily conserved core consisting of the SRP RNA and the multidomain protein SRP54. Communication between the SRP54 domains is critical for SRP function, where signal sequence binding at the M domain directs receptor binding at the GTPase domain (NG domain). These SRP activities are linked to domain rearrangements, for which the role of SRP RNA is not clear. In free SRP, a direct interaction of the GTPase domain with SRP RNA has been proposed but has never been structurally verified. In this study, we present the crystal structure at 2.5-A resolution of the SRP54-SRP19-SRP RNA complex of Methanococcus jannaschii SRP. The structure reveals an RNA-bound conformation of the SRP54 GTPase domain, in which the domain is spatially well separated from the signal peptide binding site. The association of both the N and G domains with SRP RNA in free SRP provides further structural evidence for the pivotal role of SRP RNA in the regulation of the SRP54 activity. PMID- 17846430 TI - On the trend, detrending, and variability of nonlinear and nonstationary time series. AB - Determining trend and implementing detrending operations are important steps in data analysis. Yet there is no precise definition of "trend" nor any logical algorithm for extracting it. As a result, various ad hoc extrinsic methods have been used to determine trend and to facilitate a detrending operation. In this article, a simple and logical definition of trend is given for any nonlinear and nonstationary time series as an intrinsically determined monotonic function within a certain temporal span (most often that of the data span), or a function in which there can be at most one extremum within that temporal span. Being intrinsic, the method to derive the trend has to be adaptive. This definition of trend also presumes the existence of a natural time scale. All these requirements suggest the Empirical Mode Decomposition (EMD) method as the logical choice of algorithm for extracting various trends from a data set. Once the trend is determined, the corresponding detrending operation can be implemented. With this definition of trend, the variability of the data on various time scales also can be derived naturally. Climate data are used to illustrate the determination of the intrinsic trend and natural variability. PMID- 17846431 TI - Absolute pitch: a special group of ears. PMID- 17846432 TI - Outliving colorectal cancer. PMID- 17846433 TI - Cross-Canada colorectal cancer screening programs remain elusive. PMID- 17846434 TI - New dosage limits for medical marijuana: but where's the science? PMID- 17846435 TI - Disease outbreaks in wake of Southeast Asia floods. PMID- 17846436 TI - A case of intermittent ataxia associated with migraine headaches. PMID- 17846437 TI - A case of valproate-induced hyperammonemic encephalopathy: look beyond the liver. PMID- 17846438 TI - Campylobacter and bacterial gastroenteritis. PMID- 17846439 TI - Low bone mineral density and fracture burden in postmenopausal women. AB - BACKGROUND: The study objectives were to determine fracture rates in relation to bone mineral density at various central skeletal sites, using the World Health Organization definition for osteoporosis (T-score -2.5 or less), and to contrast fracture patterns among women 50 to 64 years of age with those among women 65 years of age and older. METHODS: Historical cohort study with a mean observation period of 3.2 (standard deviation [SD] 1.5) years. The study group (16,505 women 50 years of age or older) was drawn from the Manitoba Bone Density Program database, which includes all bone mineral density results for Manitoba. Baseline density measurements for the lumbar spine and hip were performed with dual-energy x-ray absorptiometry. Outcomes included the percentage of osteoporotic fractures and the rates of fracture and excess fracture (per 1000 person-years) among postmenopausal women with osteopenia and osteoporosis relative to those with normal bone mineral density (according to the classification of the World Health Organization). RESULTS: The mean age was 65 (SD 9) years, and the mean T-scores for all sites fell within the osteopenic category. There were 765 incident fractures (fracture rate 14.5 [95% confidence interval, CI, 13.5-15.6 [per 1000 person-years). Fracture rates were significantly higher among women 65 years of age or older than among women 50-64 years of age (21.6 [95% CI 19.7-23.4] v. 8.6 [95% CI 7.5-9.7] per 1000 person-years, p < 0.001). Although fracture rates were significantly higher among women with osteoporotic T-scores, most fractures occurred in women with nonosteoporotic values (min-max: 59.7%-67.8%). INTERPRETATION: In this study, most of the postmenopausal women with osteoporotic fractures had nonosteoporotic bone mineral density values. This finding highlights the importance of considering key clinical risk factors that operate independently of bone mineral density (such as age) when assessing fracture risk. PMID- 17846440 TI - Socioeconomic status and perinatal outcomes in a setting with universal access to essential health care services. AB - BACKGROUND: The health care system in Canada provides essential health services to all women irrespective of socioeconomic status. Our objective was to determine whether perinatal and infant outcomes varied by family income and other socioeconomic factors in this setting. METHODS: We included all 92,914 women who delivered in Nova Scotia between 1988 and 1995 following a singleton pregnancy. Family income was obtained for 76,440 of these women through a confidential link to income tax records and was divided into 5 groups. Outcomes studied included pregnancy complications, preterm birth, small-for-gestational-age live birth, perinatal death, serious neonatal morbidity, postneonatal death and infant death. Logistic regression models were used to adjust for potential confounders. RESULTS: Compared with women in the highest family income group, those in the lowest income group had significantly higher rates of gestational diabetes (crude rate ratio [RR] 1.44, 95% confidence interval [CI] 1.21-1.73), preterm birth (crude RR 1.20, 95% CI 1.06-1.35), small-for-gestational-age live birth (crude RR 1.81, 95% CI 1.66-1.97) and postneonatal death (crude RR 5.54, 95% CI 2.21-13.9). The opposite was true for rates of perinatal death (crude RR 0.74, 95% CI 0.56 0.96), and there was no significant difference between the 2 groups in the composite of perinatal death or serious neonatal morbidity (crude RR 1.01, 95% CI 0.82-1.24). Adjustment for behavioural and lifestyle factors accentuated or attenuated socioeconomic differences. INTERPRETATION: Lower family income is associated with increased rates of gestational diabetes, small-for-gestational age live birth and postneonatal death despite health care services being widely available at no out-of-pocket expense. PMID- 17846441 TI - Frequency of colorectal cancer screening and the impact of family physicians on screening behaviour. AB - BACKGROUND: Mortality associated with colorectal cancer can be reduced by early detection. However, the participation of eligible people in colorectal cancer screening is thought to be inadequate. We examined the frequency of colorectal cancer screening in 4 Canadian provinces and the influence of patient contact with a family physician on the uptake of cancer screening. METHODS: We performed analyses using data from the 2003 Canadian Community Health Survey. The study population included 12,776 people at average risk for colon cancer living in British Columbia, Saskatchewan, Ontario, and Newfoundland and Labrador who were aged 50 years or older and who were eligible for colorectal cancer screening. We assessed the proportion of respondents who reported having previous colorectal cancer screening tests and the degree of contact with a family physician. RESULTS: The provincial response rates for the survey were 78.5%-87.0%. The proportion of respondents who reported any history of colorectal cancer screening was 23.5%. This value dropped to 17.6% when only up-to-date screening was considered (screening within the time frame recommended in guidelines). The proportion of people with up-to-date colorectal cancer screening varied significantly among provinces, but it was low in all provinces sampled. Contact with a family physician was associated with increased colorectal cancer screening. Compared with no physician contact, the odds of screening associated with 1-2 physician contacts in the 12 months before the survey was 1.97 (95% confidence interval [CI] 1.56-2.48], and the odds of screening associated with more than 4 contacts was 2.75 (95% CI 2.14-3.53). INTERPRETATION: Self-reported colorectal cancer screening falls well below acceptable levels. People with increased contact with a family physician are more likely than those without contact to report a history of up-to-date colorectal cancer screening. PMID- 17846442 TI - Sharing the responsibility for assessing the risk of the driver with dementia. PMID- 17846443 TI - Treating hypertriglyceridemia. PMID- 17846444 TI - Treating hypertriglyceridemia. PMID- 17846446 TI - Treating hypertriglyceridemia. PMID- 17846447 TI - Stepping down from CIHR. PMID- 17846448 TI - Open Medicine and open access. PMID- 17846449 TI - Reed Elsevier's arms business. PMID- 17846451 TI - When healers become killers: the doctor as terrorist. PMID- 17846452 TI - Screening for psychological distress in cancer patients: challenges and opportunities. PMID- 17846453 TI - Pooled results from 38 analyses of the accuracy of distress thermometer and other ultra-short methods of detecting cancer-related mood disorders. AB - Ultra-short screening tools involving fewer than five questions have been recommended as a simple method of detecting distress, anxiety, or depression in cancer settings. Such methods have practical appeal, but their diagnostic accuracy is unclear. A literature search limited to diagnostic validity studies of ultra-short screening in cancer settings identified 38 analyses, including 19 assessing the Distress Thermometer alone, involving a total of 6,414 unique patients. The pooled ability of ultra-short methods to detect depression was given by a sensitivity of 78.4%, a specificity of 66.8%, a positive predictive value (PPV) of 34.2%, and a negative predictive value (NPV) of 93.4%. Thus these tools were very good at excluding possible cases of depression but poor at confirming a suspected diagnosis. The pooled ability of ultra-short methods to detect anxiety was given by a sensitivity of 77.3% and a specificity of 56.6% (PPV, 55.2%; NPV, 80.25%) and for distress a sensitivity of 78.3% and a specificity of 66.5% (PPV, 59.7%; NPV, of 82.8%). Results using the Distress Thermometer alone were similar. Scores of integrated accuracy, using the Youden index and diagnostic odds ratio, suggested modest overall accuracy with least success in diagnosing anxiety disorders. Ultra-short methods were modestly effective in screening for mood disorders. Their rule-in ability was poorer than their rule-out ability. Ultra-short methods cannot be used alone to diagnose depression, anxiety, or distress in cancer patients but they may be considered as a first-stage screen to rule out cases of depression. PMID- 17846454 TI - The effects of signage and the physical environment on stair usage. AB - BACKGROUND: Physical activity (PA) is a health behavior that most Americans do not participate in at recommended levels. METHODS: We sought to increase PA by use of motivational signs in selected buildings. Because physical environments are known to influence PA, the relationship of building characteristics and stair usage was also assessed. One pre- and two post-intervention observations were conducted. RESULTS: The proportion of those using the stairs increased from baseline to the second data collection, (chi2 = 39.31, p < 0.01) and baseline to a final data collection (chi2 = 10.1, p < 0.01). Built environment factors, including steps to the next higher floor and the number of floors in the building were consistent predictors of stair use. With signs positioned, the visibility of the stairs while standing in front of elevators became a significant predictor of stair usage. CONCLUSIONS: Motivational signs and characteristics of built environments are associated with increased stair usage. PMID- 17846455 TI - Using the Internet to promote physical activity: a randomized trial of intervention delivery modes. AB - BACKGROUND: A growing number of the population are using the Internet for health information, such as physical activity (PA). The aim of this study was to examine the effectiveness of delivery modes for a behavior change program targeting PA. METHODS: A randomized trial was conducted with 192 subjects randomly allocated to either a face-to-face, Internet-mediated, or Internet-only arm of a 12-wk intervention. Subjects included inactive adults with Internet access. The primary outcome variable was self-reported PA, assessed at four time points. RESULTS: The results showed no group x time interaction for PA F(6, 567) = 1.64, p > 0.05, and no main effect for group F(2, 189) = 1.58, p > 0.05. However, a main effect for time F(3, 567) = 75.7, p < 0.01 was observed for each group. All groups were statistically equivalent immediately post-intervention (p < 0.05), but not at the follow-up time points (p > 0.05). The Internet-mediated and Internet-only groups showed similar increases in PA to the face-to-face group immediately post intervention. CONCLUSIONS: This study provides evidence in support of the Internet in the delivery of PA interventions and highlights avenues for future research. PMID- 17846456 TI - Associations between demographic, perceptual, and behavioral factors and support for policies encouraging active transport. AB - BACKGROUND: Policies that encourage physical activity are recommended to increase physical activity rates. Few studies have examined public support for such policies. The aim of this study was to assess support for policies that may increase active transport and correlates of this support. METHODS: A telephone survey was administered to 460 Oklahoma residents. RESULTS: Most respondents supported policies that may encourage walking and bicycling for transport. Most favored the improvement of public transportation over building new roads to address transportation concerns. In multivariate models, a positive attitude toward walking was the only variable significantly associated with support for most policy outcomes (p < 0.05). Participation in active commuting and a positive attitude toward bicycling were correlates of strong support for the creation of bike ways (p < 0.05). CONCLUSIONS: Experience with active commuting and positive attitudes toward walking and bicycling are associated with support for policies that may encourage walking and bicycling for transport. PMID- 17846457 TI - Perceived individual, social, and environmental factors for physical activity and walking. AB - BACKGROUND: Few studies have explored associations of individual, social, and environmental factors with physical activity and walking behavior. METHODS: A random-digit-dial questionnaire, which included selected individual, social, and environmental variables, was administered to 2025 adults, age 18 y and older, in two adjacent counties in a southeastern state. Logistic regressions were conducted adjusting for age, race, sex, education, and employment. RESULTS: In multivariate models, somewhat different variables were associated with physical activity versus regular walking. Self-efficacy (OR = 19.19), having an exercise partner (OR = 1.47), recreation facilities (OR = 1.54), and safety of trails from crime (OR = 0.72) were associated with physical activity level; while self efficacy (OR = 4.22), known walking routes (OR = 1.54), recreation facilities (OR = 1.57-1.59), and safety of trails from crime (OR = 0.69) were associated with regular walking behavior. CONCLUSIONS: Physical activity and walking behaviors were associated with similar variables in this study. PMID- 17846458 TI - Ambulatory activity and body mass index in white and non-white older adults. AB - BACKGROUND: The purpose of this study was to examine the extent to which physical activity (PA) is related to obesity in older adults when accounting for race/ethnicity. METHODS: Cross-sectional data were collected on 214 older adults (72.3 +/- 8.9 y; body mass index [BMI] 28.9 +/- 6.0; 151 females; 96 non-White). Measures of body height and mass were collected; BMI was calculated. PA was assessed via an electronic pedometer worn for seven consecutive days. RESULTS: "White" subjects accumulated 5036 +/- 286 steps/d. "Non-White" subjects accumulated significantly fewer steps/d (3671 +/- 253 steps/d; z = -3.45, P = 0.001). Race/ethnicity, income, age, gender, and steps/d accounted for 27.4% (P < 0.001) of the variance in BMI, with steps/d accounting for 21.2% (P < 0.001). The most influential factor in this model was PA level (beta = -0.510), followed by age (beta = -0.220), and finally gender being the least influential, but still a significant factor (beta = 0.168). CONCLUSION: Although race/ethnicity and income have been associated with obesity levels, this study shows that older adults who accumulate more ambulatory activity tend to have healthier levels of BMI irrespective of race/ethnicity or income. PMID- 17846459 TI - Should all steps count when using a pedometer as a measure of physical activity in older adults? AB - PURPOSE: The aim of this study was to determine if feedback on step counts from a pedometer encourages participants to increase walking. METHODS: Randomly recruited older adults (n = 105) were asked to wear a pedometer for 2 wk. Half the participants were asked to monitor and record daily step counts during week 1 (feedback), then seal the pedometer shut during week 2 (no feedback). Half completed the study in reverse order. Self-reported walking was assessed via telephone interviews. RESULTS: Significantly more steps were recorded per day (approximately 400 steps per day) when participants (n = 103, 63% women; mean BMI 25 +/- 4) monitored their daily step count [t(102) = -2.30, P = 0.02)] compared to the no feedback condition. There was no statistically significant difference in self-reported walking (P = 0.31) between feedback conditions. CONCLUSION: The difference in daily step counts observed between conditions, while statistically significant, may not be considered clinically significant. Further, the non significant difference in self-reported walking between conditions suggests that feedback on daily step counts from a pedometer does not encourage participants to increase their walking. PMID- 17846460 TI - Step-counter determined walking in youth in Colorado. AB - BACKGROUND: Results from a statewide telephone survey of walking showed that the average adult in Colorado takes 6804 steps/d, and that steps/d were negatively associated with body mass index. No similar data exist for children. METHODS: As part of the Colorado survey, demographic information was obtained from parents for 116 children. A subsample of 59 children and adolescents (age 10 to 17 y) agreed to wear a step counter for four consecutive days. RESULTS: The youth reported taking an average of 7902 steps/d. There was a trend for children's steps/d to be positively associated with parents' steps/d and negatively associated with TV watching. CONCLUSION: This sample of children is not large enough to be considered a representative sample of Colorado youth, but this cross sectional study provides some much needed information about steps/d in children and generates some interesting hypotheses about steps/d and other measures of health and overweight. PMID- 17846461 TI - Physical activity-related injury and body mass index among US high school students. AB - BACKGROUND: Few studies have focused on the relationship between physical activity-related (PA) injury and overweight among youth. METHODS: We analyzed data from the 2001 and 2003 Youth Risk Behavior Surveys (n = 28,815). Logistic regression was used to examine the independent effects of BMI and frequency of participation in vigorous activity, moderate activity, strengthening exercises, physical education (PE) classes, and team sports on the likelihood of PA injury. RESULTS: Approximately 14% of females and 19% of males reported seeing a doctor or nurse during the previous 30 d for an injury that happened while exercising or playing sports. PA injury was associated with participation in team sports, strengthening exercises, and (among females) vigorous physical activity. Controlling for type and frequency of physical activity, injury was not associated with being overweight (BMI >or= 95th percentile). CONCLUSIONS: Moderate physical activity and school PE classes may provide relatively low-risk alternatives for overweight youth who need to increase their physical activity. PMID- 17846463 TI - Inflammation and cardiopulmonary bypass. PMID- 17846462 TI - Validation of a historical physical activity questionnaire in middle-aged women. AB - BACKGROUND: Historical physical activity (PA) questionnaires assess relationships between past PA and chronic diseases. The 4-Corner's Historical Physical Activity Questionnaire (HPAQ) was validated in 78 middle-age women. METHODS: In 1996 and 1998, women kept PA records (PAR) for four consecutive days while wearing Caltrac accelerometers. In 2001, the same women recalled their past PA levels using the HPAQ. PA levels from the HPAQ were compared to PARs and the Caltrac. Race adjusted Spearman correlations determined validity. RESULTS: Low to modest correlations existed between PA (min/wk and MET-min/wk) from the HPAQ and PARs for moderate (r = 0.16 and 0.14, respectively), vigorous PA (r = 0.26 and 0.27, respectively; P < 0.05) and moderate-vigorous PA (r = 0.20 and 0.17, respectively). Moderate and moderate-vigorous, but not vigorous PA was positively related to energy expenditure expressed as kilocalories (r = 0.23, P < 0.05 and 0.22, -0.03, respectively) or PA volume (MET-min/wk) (r = 0.29, 0.29, P < 0.05 and 0.10, respectively). CONCLUSION: The HPAQ can produce valid estimates of women's past moderate and vigorous PA levels. PMID- 17846464 TI - Cardiovascular morbidity association with surgery: perspectives and new findings. PMID- 17846465 TI - Suppression of the inflammatory response to cardiopulmonary bypass. AB - The inflammatory response to major surgery, especially cardiac surgery using cardiopulmonary bypass (CPB) is now a well established entity. A whole body inflammatory response can lead to severe organ dysfunction, postoperative bleeding disorders, respiratory distress syndrome and sometimes death. There is, however, controversy over various methods and their efficacy towards suppression of this response. We studied forty consecutive patients undergoing coronary artery bypass grafting (CABG) using CPB. Ten patients in group A served as control while ten patients in group B received piroxicam, a non steroidal anti inflammatory drug (NSAID). Ten patients in group C received aprotinin, a kallikrein inhibitor and ten patients in group D underwent haemofiltration during CPB. Inflammatory response by way of increase in total white blood cell (WBC) count (p<0.007), decrease in lymphocyte count (p<0.005), increase in C-reactive protein (CRP, p <0.005) was observed in all four groups at 24 hour after CPB. A decrease in complement C3 and C4 (p<0.01) was observed in groups A and C at 24 hours after CPB. The response observed was not severe enough to cause any organ damage in any group. None of the methods studied could effectively suppress the inflammatory response to CPB but the response was altered in some way by each method. PMID- 17846466 TI - Emergency mitral valve replacement for traumatic mitral insufficiency following balloon mitral valvotomy: an early haemodynamic study. AB - Acute severe mitral insufficiency may occur during percutaneous transvenous balloon mitarl valvotomy. Urgent surgical intervention in the form of mitral valve repair or replacement may be necessary in these patients. The haemodynamic measurements at various stages in these patients were obtained and compared with those of patients undergoing elective mitral valve replacement for chronic mitral regurgitation. Between September 1995 and December 1947, urgent mitral valve replacement was performed in 14 patients out of a total of 1688 patients who underwent balloon mitral valvotomy. Haemodynamic measurements could be obtained in 7 of these patients and they constituted group I. Eight other patients undergoing elective mitral valve replacement during the same period for chronic mitral regurgitation constituted group II. Standard haemodynamic measurements were obtained at the following stages: (1) Baseline- 20-30 min after endotracheal intubation; (2) stage 1- 20-30 min after termination of the cardiopulmonary bypass: (3) stage 2- four hours after the patient was transferred to ICU and (4) stage 3-30 min after extubation. All the patients were suffering from severe pulmonary hypertension. However, the indices of pulmonary artery hypertension such as mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance as well as right ventricular systolic and end diastolic pressures did not decrease after surgery in group I. In contrast, in group II, there was significant decrease in mean pulmonary artery pressure (p<0.05), pulmonary capillary wedge pressure (p<0.05), right ventricular systolic (p<0.001) and end-diastolic pressures (p<0.05) at stage 1. These changes persisted throughout the study period. Pulmonary vascular resistance showed a decreasing trend, but attained statistical significance at stage 1 only. Two patients died; one of intractable cardiac failure and another from septicaemia and multiple organ failure in group I, but there were no deaths in group II. Reactive pulmonary hypertension secondary to acute mitral regurgitation may not recover immediately following mitral valve replacement and may be responsible for poor outcome in these patients. PMID- 17846467 TI - Oxygenation of crystalloid cardioplegia. AB - A simple economical apparatus for oxygenation of cold crystalloid cardioplegic solutions is presented. It is sterile, practically feasible for use in open heart surgery, provides a PO2 of 98.7 kPa and sustains it for a period of more than 20 minutes. PMID- 17846468 TI - Role of Preoperative Upper Gastrointestinal Endoscopy in Preventing postoperative Upper Gastrointestinal Bleed in Patients Undergoing CABG. AB - One hundred and three patients (Group A), mean age 55.81 +/- 8.54 years, 94 males and 9 females, scheduled for coronary artery bypass graft (CABG) surgery were subjected to preoperative upper gastro-intestinal (UGI) endoscopy. 51.5% of these were found to have significant mucosal lesions in the UGI tract. Twenty one (20.4%) had severe lesions which could have bled, warranting postponement of their surgery. All of these 21 were treated with Omeprezole 20 mg / day for a mean of 35.87 +/- 4.64 days and subjected to check endoscopy after the treatment. 16 of these 21 patients were taken up for CABG after the lesions had healed. Five deferred surgery. None of the 103 patients had a postoperative UGI bleed. A retrospective analysis of 1274 patients (group B) was carried out for number of patients (42) having postoperative UGI bleed. The results of group A and group B were then compared. Patients in group A had significant lower incidence of postoperative UGI bleed than those in group B. Postoperative hospital stay in patients of UGI bleed in group B was 24.71 +/- 20.88 (range 8 days - 129 days). In group A it was 14.34 +/- 12.44 days (range 7 days - 88 days). The difference is statistically highly significant. It appears that patients who have postoperative UGI bleed probably bleed from pre existing lesions. We conclude that preoperative UGI endoscopy is a valuable tool in preventing postoperative UGI bleed. PMID- 17846469 TI - The inflammatory response to extracorporeal circulation. PMID- 17846470 TI - Other uses of tube changer. AB - Traditionally major surgical procedures are contemplated in tracheobronchial pathology as the first line of management. Efficient and skillful use of airway equipment can help in the management and prevention of significant perioperative morbidity. Three cases of airway pathology (tracheal stenosis, bronchial stenosis and tracheal tumour) which were managed with the help of airway equipment such as fibreoptic bronchoscope, Cook's and Patil tube changers are presented. The techniques are simple and safe and may help the surgeons to 'buy' time to plan definitive treatment. PMID- 17846471 TI - An unusual case of steep rise of blood glucose during cardiopulmonary bypass. AB - Disturbances of blood glucose insulin relationships have been repeatedly observed during and after cardiac surgery. We report a case where a blood sugar level of 2000 mg/dl was encountered after commencement of cardiopulmonary bypass and discuss its management. PMID- 17846472 TI - Anaesthesiologist in the net. AB - The Internet is expanding very rapidly with more people joining hands and minds everyday. The encouraging news is that a lot of these people are medical professionals. This makes for a scientific community with better interaction and understanding of problems relating to health care. As anaesthesiologists, we are at an advantage that our discipline allows maximal interaction with related subjects like paediatrics, critical care, pulmonology, cardiology and emergency medicine. This article will deal with some interesting websites relating mainly to fields associated with cardiovascular anaesthesia. PMID- 17846473 TI - Dare we interfere with the haemostatic balance? PMID- 17846474 TI - Modified ultrafiltration following cardiopulmonary bypass in paediatric open heart surgery. PMID- 17846475 TI - Efficacy of minimal dose aprotinin in open heart procedures. AB - In a randomized double blind study, 30 patients posted for CABG surgery were assigned to 3 groups of 10 each. Group A received 140 mg (1,000,000 KIU) of aprotinin after induction of anaesthesia but before sternotomy, an equal amount in the pump prime and a maintenance dose of 70 mg/hr throughout cardiopulmonary bypass (standard dose). Group B received placebo after induction of anaesthesia, 70 mg (500,000 KIU) aprotinin in the pump prime with a placebo as a maintenance dose (minimal dose). Group C received a placebo after induction of anaesthesia, in the prime and as a maintenance dose (control group). The mean chest closure times were insignificantly lower in the aprotinin groups; 35.83 +/- 13.93 mins in group A and 37.5 +/- 10 mins in group B as against 57.25 +/- 26.54 mins in group C. Post-operative haemoglobin loss was significantly lower (P<0.01) in aprotinin groups, 5.42 +/- 1.6 gm in group A and 6.28 +/- 2.49 gms in group B, as against 39.77 +/- 27.51 gm in group C. Whole blood transfusion requirement was also significantly reduced from 4.12 +/- 1.79 units in the control group to 2.5 +/- 0.75 units in group A (p < 0.05) and 2 +/- 1.3 units (p<0.01) in group B. We conclude that a minimal dose of aprotinin 70 mg (500,000 KIU) is effective in reducing postoperative blood loss, blood transfusion requirement and is economical. PMID- 17846476 TI - Coronary Artery Bypass Grafting without Cardiopulmonary Bypass: Improvement in Cardiac Function Following Enflurane Anaesthesia during Coronary Occlusion. AB - Severe adverse effects, especially neurologic complications after cardiopulmonary bypass have lead to the development of techniques for performing coronary artery bypass graft surgery without cardiopulmonary bypass. Laboratory and clinical studies confirmed the positive role of enflurane anaesthesia in preventing myocardial dysfunction following an ischaemic interval. The aim of this study was to evaluate the haemodynamic response to enflurane anaesthesia during single graft coronary bypass surgery without cardiopulmonary bypass. Twenty one patients were divided randomly into two groups: control and enflurane groups. Haemodynamic parameters and those derived from a pulmonary artery catheter were recorded and analysed. In the enflurane group, the amount of fentanyl administered was considerably less than in the control group: 25.7 +/- 3.8 microg/kg vs 36.8 +/- 1.6; p=0.03. The mean arterial pressure during enflurane administration was lower than in control group, but the difference was not significant. Despite a dearease in left ventricular function during the performance of the anastomosis in the enflurane group, a significant recovery was noted after 20 minutes of reperfusion: cardiac index increased from 1.4 +/- 0.1 to 1.85 +/- 0.1 L/min/m2 and left ventricular stroke work index from 15.8 +/- 1.1 to 27.7 +/- 6.7 g.m.m2 . In the control group, the deterioration in cardiac function observed during the graft anastomosis did not recover till the end of the surgical procedure. We conclude that enflurane anaesthesia may be a positive addition to fentanyl-based anaesthesia by improving myocardial function following CABG without bypass surgery. PMID- 17846477 TI - Clinical efficacy of clonidine as an adjunct to anaesthesia for coronary artery bypass graft surgery. AB - Clonidine, a preferential alpha 2 adrenergic agonist has been reported to have perioperative effects including reduction of anaesthetic requirements, improving haemodynamic stability and providing analgesia, however its clinical usefulness in cardiac surgery is not widely studied. Thirty-four consecutive patients undergoing coronary artery bypass graft surgery (CABG) were preoperatively administered clonidine and studied for its possible desirable effects. Seventeen patients (Gr B) received 2 microg/kg clonidine orally the previous night and again one hour prior to surgery. Seventeen patients did not receive the drug and served as control (Gr A). Heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), requirement of isoflurane, requirement of nitroglycerin, sedation score, extubation score and urine output were studied throughout the perioperative period. HR was observed to be lower at all time points in the clonidine group though the difference between groups was not statistically significant (p > 0.1). MAP was higher at all time points and significantly so after intubaton in the control group (P < 0.01). Patients receiving clonidine required significantly less isoflurane and nitroglycerin (P < 0.05). sedation score was significantly higher in the clonidine group. Other aspects studied were comparable in both groups. At the doses described in this study, clonidine seems to be a safe useful adjunct to anaesthesia for CABG surgery. PMID- 17846478 TI - Comparative evaluation of cardiovascular effects of sevoflurane and isoflurane in patients with ischaemic heart disease undergoing non-cardiac surgery. AB - Twenty three adult patients with ischaemic heart disease undergoing elective non cardiac surgery were studied. Induction of anaesthesia was similar for each patient and included thiopentone (4-5 mg/kg), morphine (0.1 mg/kg) and vecuronium (0.1 mg/kg). Additional morphine and vecuronium were used when necessary. All these patients were maintained with either sevoflurane (n=11) or isoflurane (n=12). The inhaled anaesthetics were titrated to achieve adequate clinical 'depth of anaesthsia' and to maintain mean arterial pressure within 20% of the pre-induction values. Heart rate, blood pressure and rate-pressure product were recorded during the maintenance phase of anaesthsia. ST-T changes were also monitored during this period. There was a tendency for heart rates to be significantly higher shortly after skin incision till the end of procedure in the isoflurane group, while in the sevoflurane group heart rate remained stable during the surgical procedure. Both systolic and diastolic blood pressure remained similar in both groups. The rate pressure product was higher in the isoflurane group than in the sevoflurane group at 30 min Post-incision. The data suggests that sevoflurane is not associated with untoward cardiovascular changes in ischaemic heart disease patients undergoing non-cardiac surgery. PMID- 17846479 TI - Comparison of intubating conditions and haemodynamic effects of rocuronium with vecuronium in patients with poor left ventricular ejection fraction undergoing coronary artery bypass graft surgery. AB - To compare the haemodynamic effects and intubating conditions of rocuronium and vecuronium, 20 patients of either sex with poor left ventricular function (ejection fraction <35%) scheduled for coronary artery bypass surgery were randomly divided into two equal groups. All patients were premedicated with lorazepam and morphine and induced with morphine, midazolam, thiopentone and either vecuronium (0.1 mg/kg) or rocuronium (0.6 mg/kg) as muscle relaxant. All patients were intubated after 3 minutes in the vecuronium group and 90 seconds in the rocuronium group by the same anaesthesiologist. Monitoring in all cases included neuromuscular (train of four- TOF), systemic and pulmonary arterial pressures, cardiac output and calculated haemodynamic variables. Demographic (age, sex and mean ejection fraction) and haemodynamic variables were comparable in both the groups. A significant suppression of the TOF in the vecuronium group was observed despite better intubating conditions in the rocuronium group. The heart rate at 3 minutes and mean arterial pressure at 1 minute was higher in the vecuronium group as compared to the rocuronium group. There were no other significant haemodynamic differences in both the groups. We conclude that rocuronium does provide better intubating conditions at 90 seconds than vecuronium at 3 minutes with no significant differences in the haemodynamic parameters between the two; however, the train of four response does not correlate with intubating conditions. PMID- 17846480 TI - Current concepts in cardiopulmonary resuscitation. AB - For many people cardiac arrest is a natural ending of a long and productive life. A substantial number of humans, however, are struck by this event too early in life with tragic consequences including financial problems for both family and society. A recent review of in-hospital cardiac arrests found a wide variation in the reported survival to discharge ranging from 0% to 28.9% with a mean of 14%1. This is largely explained by underlying diseases. In out-of-hospital cardiac arrests the survival to discharge is similar2, 3. fewer than 3% of cardiac arrest victims leave the hospital alive and return to productive lives. The reasons for these depressing results are multifactorial including rapidity and sequence with which the resuscitation interventions are delivered. Bystander CPR is an important link in "the chain of survival" before more advanced interventions will be available at the scene. 4 CPR training programmes for lay people have been organised in many countries with millions of people trained in basic CPR. It is important to continue this education of lay people since at the moment early bystander CPR, besides defibrillation, is probably the single most important intervention. The concept of early activation of the emergency medical System, early basic life support (BLS), including precordial compression and artificial ventilation, early defibrillation, and early advanced cardiac life support (ACLS), could achieve 25-40% survival rates.3 These concepts for emergency cardiac care have been supported by the American Heart Association5 as well as the European Resuscitation Counil.6 Advanced cardiac life support protocols combine pharmacological and mechanical interventions to restore spontaneous circulation (ROSC) and is based on four components: early defibrillation, administration of drugs, ventilation (oxygenation), and circulatory support. PMID- 17846481 TI - Anaesthetic considerations in a patient with wolff-Parkinson-white syndrome. AB - Wolff-Parkinson-White syndrome is an important variant of pre-excitation syndromes caused by congenital atrioventricular accessory pathway. It can lead to various types of serious cardiac arrhythmias. We describe general anaesthesia management using fentanyl-vecuronium-halothane technique to achieve haemodynamic stability. PMID- 17846483 TI - Artificial blood substitutes. PMID- 17846482 TI - Transfemoral extraction of knotted pulmonary artery catheter in right atrium. AB - Knotting of a pulmonary artery catheter (PAC) is a rare complication which is usually seen to occur in the right ventricle. We describe knotting of a PAC in the right atrium and its extraction by non surgical means through the femoral route. PMID- 17846484 TI - Blood substitutes - the current state of the art. PMID- 17846485 TI - "Fast-tracking" in patients undergoing coronary artery surgery with severely impaired left ventricular function. AB - Cost containment and efficient resource utilization are motivating anaesthesiologists to early tracheal extubation of cardiac surgical patients. Fast track cardiac anaesthesia is both safe and cost-effective. We studied 45 patients with LVEF = 40% who underwent coronary revascularization and were put on the same fast track principle as those with normal ventricular function. Of these 31 patients (68.8%) had recent (<2 weeks) cardiac events requiring hospitalization. Acute myocardial infarction was documented in 8 patients (17.7%) and 23 (51.1%) had unstable angina. Congestive failure was present in 13 (28.9%) patients. Preoperative intravenous pharmacological support was needed in 17 (37.7%) patients, mechanical ventilation in 2 (4.5%) and IABP support in 1 (2.3%) patient. Anaesthetic management of these patients hinged on reduced usage of narcotics and muscle relaxants to facilitate early extubation. Operative strategy adopted was that of optimal revascularization. Beating heart surgery was adopted particularly in patients with low ejection fraction to avoid the attendant systemic and myocardial ill effects of cardiopulmonary bypass (CPB), especially in those who have had recent myocardial insults. Coronary surgery was performed on beating heart in 18 (40%) patients, while the other 27 (60%) patients were revascularised on CPB support. Of the 44 operative survivors, early extubation (<4 hours) was performed in 37 (84%) patients. Only 7 (16%) patients required ventilation for more than 24 hours. 3 out of these 7 patients were ventilated due to pulmonary reason and other 4 were ventilated since they were on IABP support. ICU stay was less than 24 hrs for 34/42 (80.9%) and hospital stay less than 6 days in 24/40 (60%). Fast tracking in cardiac surgery can be achieved with safety even in patients with impaired LV function. PMID- 17846486 TI - Halothane modifies oxygen free radical activity on the voltage-sensitive calcium channels in canine myocardial membranes. AB - BACKGROUND: The functional derangements in the myocyte cell membrane, the sarcolemma, during short myocardial ischaemia and reperfusion are attributed to excessive influx of Ca2+ ions via the voltage-sensitive calcium channels (VSCC) and to the free radical-related injury. However, it is unclear whether the primary changes in the VSCC should be attributed to the ischaemic effect or to free radical action on channel constituents. Under these circumstances of ischaemia and reperfusion, volatile anaesthetics have exhibited protective properties on the myocardium. The present study is aimed at characterizing the effect of artificially-generated oxygen free radicals on the VSCC in canine sarcolemma, independently of the effect of ischaemia, and the effect of halothane on the membranes during the surge of the free radicals. METHODS: Selective production of free radicals (O2-, CO2-) was made by gamma irradiation of isolated sarcolemma membranes with 137 Cesium (Cs), in the presence of 20 mM sodium formate. Control studies were performed without formate in the aqueous solution. In an additional group, liquid halothane (3 microl. 1.9 vol%) was added to the sarcolemma / formate preparation immediately prior to irradiation. The effects of free radicals on the VSCC was evaluated by redioligand binding studies of the calcium channel blocker [3H] isradipine to the sarcolemma. RESULTS: In six control studies, the rediolytic aqueous species produced by 137 Cs irradiation resulted in unchanged [3 H] isradipine binding. In the presence of formate [n=9], the free radicals have caused a 23% to 25% decrease, both, in density and dissociation constant (P=0.05) of [3 H]isradipine to the VSCC binding sites. When superoxide radicals were generated in the presence of 1.9% halothane and formate (n=6), a significant increase in maximal binding capacity (by 55% +/- 2; P<0.01) and in the dissociation constant (by 209% +/- 35, P<0.01) occurred. CONCLUSION: Oxidative free radicals which are generated by gamma irradiation exerted minimal changes on the normal function of the VSCC as reflected by the non-significant changes in [3 H] isradipine specific binding. Introduction of halothane into free radical generating system causes acute perturbations to the VSCC kinetics, and does not provide protection to the cardiac membranes. PMID- 17846487 TI - Haemostatic effects of crystalloid vs colloid prime in patients undergoing coronary artery bypass grafting. AB - The controversy surrounding the use of a colloid or a crystalloid prime in the cardiopulmonary circuit still continues and is a matter of conjecture and an unresolved issue. To evaluate the effect of 4% modified fluid gelatin on haemostasis by measurement of haemostatic variables after cardiopulmonary bypass surgery, we studied 40 patients. They were randomly assigned to 2 groups of ringer lactate and 4% modified fluid gelatin priming solution. The study conclusively proved that 4% modified fluid gelatin has no significant effect on haemostasis and could be recommended as a priming fluid in cardiopulmonary bypass circuit. PMID- 17846488 TI - Sevoflurane for induction and intubation in children undergoing congenital cardiac surgery. AB - The induction and intubation characteristics of sevoflurane were studied prospectively in 23 children, aged 3 months to 6 years (mean 24 +/- 20.25), undergoing repair of congenital cardiac defects. After premedication with syrup chloral hydrate (75mg/kg orally), anaesthesia was induced with 8% sevoflurane and 50% nitrous oxide in oxygen. Nasal endotracheal intubation was performed once the pupils were small and central, without the use of neuromuscular blocking agents or opioids. Characteristics of induction and intubating conditions were recorded. Induction time (from application of face mask to loss of eyelash reflex) was 43.7 +/- 4.57 secs (mean +/- SD). Mean intubation time was 149.1 +/- 15.6 secs. Intubating conditions were excellent in 21 patients (91.3%) and good in 2 patients (80.7%). Haemodynamic parameters (heart rate, rhythm, and systolic blood pressure) were recorded at loss of eyelash reflex, immediately before intubation and at 1, 3 and 5 min after intubation. All children remained haemodynamically stable throughout induction and there were no adverse airway events. PMID- 17846489 TI - Hyperalimentation in the critically ill cardiac surgical patient. PMID- 17846490 TI - Sevoflurane for trans-sternal thymectomy in myasthenia gravis. AB - Myasthenic gravis (MG) is an autoimmune disease associated with acetylcholine receptor deficiency. Patients with MG exhibit increased sensitivity to non depolarising muscle relaxants. In an attempt to avoid neuromuscular blockers, we used sevoflurane in two myasthenic patients undergoing trans-sternal thymectomy. Inhalation of 8% sevoflurane in oxygen using vital capacity technique produced rapid, pleasant and smooth induction and provided good tracheal intubating conditions. In both patients anaesthesia was maintained with 1.5-2% end-tidal concentration of sevoflurane and nitrous oxide in oxygen without adjunctive neuromuscular blocking agents. There were minimal changes in cardiovascular variables and recovery was faster. It is suggested that sevoflurane may be the main anaesthetic for both induction and maintenance in myasthenic patients undergoing trans-sternal thymectomy. PMID- 17846491 TI - Perforated peptic ulcer after cardiac surgery. AB - Although there are many causes of ulcer disease in postoperative period, hypoperfusion during cardiopulmonary bypass and advanced age are two key causes. We came across two cases of peptic ulcer perforation after coronary bypass graft surgery where these two common factors were absent. We have discussed various aetiolofical factors responsible for genesis of gastrointestinal ulcers in patients undergoing cardiac surgery using cardiopulmonary bypass. PMID- 17846492 TI - Anaesthesiologist in net. PMID- 17846493 TI - Development of natural killer cells from hematopoietic stem cells. AB - Natural killer (NK) cells play a crucial role in innate immune system and tumor surveillance. NK cells are derived from CD34+hematopoietic stem cells and undergo differentiation via precursor NK cells in bone marrow (BM) through sequential acquisition of functional surface receptors. During differentiation of NK cells, many factors are involved including cytokines, membrane factors and transcription factors as well as microenvironment of BM. NK cells express their own repertoire of receptors including activating and inhibitory receptors that bind to major histocompatibility complex (MHC) class I or class I-related molecules. The balance between activating and inhibitory receptors determines the function of NK cells to kill targets. Binding of NK cell inhibitory receptors to their MHC class I-ligand renders the target cells to be protected from NK cell-mediated cytotoxicity. Thus, NK cells are able to discriminate self from non-self through MHC class I-binding inhibitory receptor. Using intrinsic properties of NK cells, NK cells are emerging to apply as therapeutic agents against many types of cancers. Recently, NK cell alloactivity has also been exploited in killer cell immunoglobulin-like receptor mismatched haploidentical stem cell transplantation to reduce the rate of relapse and graft versus host disease. In this review, we discuss the basic mechanisms of NK cell differentiation, diversity of NK cell receptors, and clinical applications of NK cells for anti-cancer immunotherapy. PMID- 17846494 TI - Redifferentiation of dedifferentiated chondrocytes on chitosan membranes and involvement of PKCalpha and P38 MAP kinase. AB - To investigate the effects of chitosan on the redifferentiation of dedifferentiated chondrocytes, we used chondrocytes obtained from a micromass culture system. Micromass cultures of chick wing bud mesenchymal cells yielded differentiated chondrocytes, but these dedifferentiated during serial monolayer subculture. When the dedifferentiated chondrocytes were cultured on chitosan membranes they regained the phenotype of differentiated chondrocytes. Expression of protein kinase C (PKC) increased during chondrogenesis, decreased during dedifferentiation, and increased again during redifferentiation. Treatment of the cultures with phorbol 12-myristate 13-acetate (PMA) inhibited redifferentiation and down-regulated PKC. In addition, the expression of p38 mitogen-activated protein (MAP) kinase increased during redifferentiation, and its inhibition suppressed redifferentiation. These findings establish a culture system for producing chondrocytes, point to a new role of chitosan in the redifferentiation of dedifferentiated chondrocytes, and show that PKC and p38 MAP kinase activities are required for chondrocyte redifferentiation in this model system. PMID- 17846495 TI - Identification of QTLs for some agronomic traits in rice using an introgression line from Oryza minuta. AB - Wild progenitor species provide potential gene sources for complex traits such as yield and multiple resistances to biotic and abiotic stresses, and thus are expected to contribute to sustainable food supplies. An introgression line 'IR71033-121-15' was derived from a wild species Oryza minuta (2n = 48, BBCC, Acc No. 101141) at IRRI. Introgression analysis using 530 SSR and STS markers revealed that at least 14 chromosomal segments distributed over 12 chromosomes had been introgressed from O. minuta. An F2:3 population from the cross between IR71033 and Junambyeo (a Korean japonica cultivar) consisting of 146 lines was used for quantitative trait loci (QTL) analysis of 16 agronomic traits. A total of 36 single-locus QTLs (S-QTLs) and 45 digenic epistasis (E-QTLs) were identified. In spite of it's inferiority of O. minuta for most of the traits studied, its alleles contributed positively to 57% of the QTLs. The other QTLs originated from either parent, IR71033 or Junambyeo. QTLs for phenotypically correlated traits were mostly detected on introgressed segments. Fourteen QTLs corresponded to QTLs reported earlier, indicating that these QTLs are stable across genetic backgrounds. Twenty-two QTLs controlling yield and its components had not been detected in previous QTL studies. Of these, thirteen consisted of potentially novel alleles from O. minuta. QTLs from O. minuta introgression could be new sources of natural variation for the genetic improvement of rice. PMID- 17846496 TI - Crystal structure of TTC0263, a thermophilic TPR protein from Thermus thermophilus HB27. AB - The hypothetical protein TTC0263 of Thermus thermophilus HB27 is a thermophilic tetratricopeptide repeat (TPR)-containing protein. In the present study, the TPR region (residues 26-230) was resolved at 2.5 A with R-factors of R/Rfree = 23.6%/28.6%. TTC0263 consists of 11 helices that form five TPR units. Uniquely, it contains one atypical "extended" TPR (eTPR) unit. This comprises extended helical residues near the loop region of TTC0263, such that the helical length of eTPR is longer than that of the canonical TPR sequence. In addition, the hybrid TPR domain of TTC0263 possesses oligomer-forming characteristics. TPR domains are generally involved in forming multi-subunit complexes by interacting with each other or with other subunit proteins. The dynamic structure of TTC0263 described here goes some way to explaining how TPR domains mediate the formation of multi subunit complexes. PMID- 17846497 TI - Differential expression of three catalase genes in the small radish (Rhaphanus sativus L. var. sativus). AB - Three catalase cDNA clones were isolated from the small radish (Raphanus sativus L.). Their nucleotide and deduced amino acid sequences showed the greatest homology to those of Arabidopsis. Genomic Southern blot analysis, using RsCat1 cDNA as a probe, showed that catalases are encoded by small multigene family in the small radish. Nondenaturing polyacrylamide gels revealed the presence of several catalase isozymes, the levels of which varied among the organs examined. The isozyme activities were assigned the individual catalase genes by Northern analysis using total RNA from different organs. The three catalase genes were differentially expressed in response to treatments such as white light, xenobiotics, osmoticum, and UV. Their expression in seedlings was controlled by the circadian clock under a light/dark cycle and/or in constant light. Interestingly, RsCat1 transcripts peaked in the morning, while those of RsCat2 and RsCat3 peaked in the early evening. Our results suggest that the RsCat enzymes are involved in defense against the oxidative stress induced by environmental changes. PMID- 17846498 TI - Gene transcription in the leaves of rice undergoing salt-induced morphological changes (Oryza sativa L.). AB - We describe the gene expression profile of third leaves of rice (cv. Nipponbare) seedlings subjected to salt stress (130 mM NaCl). Transcripts of Mn-SOD, Cu/Zn SOD,cytosolic and stromal APX, GR and CatB were regulated, whereas expression of thylakoid-bound APX and CatA were down-regulated. The levels of the compatible solute proline and of transcripts of its biosynthetic gene, Delta1-pyrroline-5 carboxylate synthetase (P5CS), were strongly increased by salt stress. Interestingly, a potential compatible solute, gamma-aminobutyric acid (GABA), was also found to be strongly induced by salt stress along with marked up-regulation of transcripts of GABA-transaminase. A dye-swap rice DNA microarray analysis identified a large number of genes whose expression in third leaves was altered by salt stress. Among 149 genes whose expression was altered at all the times assayed (3, 4 and 6 days) during salt stress, there were 47 annotated novel genes and 76 unknown genes. These results provide new insight into the effect of salt stress on the expression of genes related to antioxidant enzymes, proline and GABA as well as of genes in several functional categories. PMID- 17846499 TI - Identification of new microsatellite markers in Panax ginseng. AB - Microsatellites, also called simple sequence repeats (SSR), are very useful molecular genetic markers commonly used in crop breeding, species identification and linkage analysis. In the present study, we constructed a microsatellite enriched genomic library of Panax ginseng, and identified 251 novel microsatellite sequences. Tri-nt repeat units were the most abundant (46.6%), followed by di-nt repeats (35.5%). The (AG)n motif was most common (23.1%), followed by the (AAC)n motif (22.3%). From the genotyping of 94 microsatellites using marker-specific primer sets, we identified 11 intraspecific polymorphic markers as well as 14 possible interspecific polymorphic markers differing between P. ginseng and P. quinquefolius. The exact allele structures of the polymorphic markers were determined and the alleles were named. This study represents the first report of the bulk isolation of microsatellites by screening a microsatellite-enriched genomic library in P. ginseng. The microsatellite markers could be useful for linkage analysis, genetic breeding and authentication of Panax species. PMID- 17846500 TI - Toxic levels of amyloid beta peptide do not induce VEGF synthesis. AB - Alzheimer's disease is a neurodegenerative disorder associated with progressive loss of cognitive function and memory. Amyloid beta peptide (Abeta) is the major component of senile plaques and is known to exert its cytotoxic effect mainly by producing H2O2. Vascular endothelial growth factor (VEGF) is elevated in the cerebrospinal fluid (CSF) and brain of AD patients, and H2O2 is one of the factors that induce VEGF. Therefore, we tested whether Abeta might be responsible for the increased VEGF synthesis. We found that Abeta induced the production of H2O2 in vitro. Comparison of the amount of H2O2 required to induce VEGF synthesis in HN33 cells and the amount of H2O2 produced by 10 muM Abeta1-42 in vitro suggested that a toxic concentration of Abeta might induce VEGF synthesis in these cells. However, toxic concentrations of Abeta failed to induce VEGF synthesis in several cell systems. They also had no effect on antioxidant enzymes such as glutathione peroxidase, catalase, and peroxiredoxin in HN33 cells. Cu2+, Zn2+ and Fe3+ are known to accumulate in the brains of AD patients and promote aggregation of Abeta, and Cu2+ by itself induces synthesis of VEGF. However, there was no synergistic effect between Cu2+ and Abeta1-42 in the induction of VEGF synthesis and Zn2+ and Fe3+ also had no effect on the synthesis of VEGF, alone or in combination with Abeta. PMID- 17846501 TI - A simple method for combined fluorescence in situ hybridization and immunocytochemistry. AB - By combining in situ hybridization (ISH) and immunocytochemistry (IC), microscopic topological localization of mRNAs and proteins can be determined. Although this technique can be applied to a variety of tissues, it is particularly important for use on neuronal cells which are morphologically complex and in which specific mRNAs and proteins are located in distinct subcellular domains such as dendrites and dendritic spines. One common technical problem for combined ISH and IC is that the signal for immunocytochemical localization of proteins often becomes much weaker after conducting ISH. In this manuscript, we report a simplified but robust protocol that allows immunocytochemical localization of proteins after ISH. In this protocol, we fix cultured cortical or hippocampal neurons with 4% paraformaldehyde (PFA), rinse briefly in PBS, and then further fix the cells with C methanol. Our method has several major advantages over previously described ones in that (1) it is simple, as it is just consecutive routine fixation procedures, (2) it does not require any special alteration to the fixation procedures such as changes in salt concentration, and (3) it can be used with antibodies that are compatible with either methanol (MeOH-) or PFA-fixed target proteins. To our best knowledge, we are the first to employ this fixation method for fluorescence ISH + IC. PMID- 17846502 TI - Quantitative trait loci associated with functional stay-green SNU-SG1 in rice. AB - During monocarpic senescence in higher plants, functional stay-green delays leaf yellowing, maintaining photosynthetic competence, whereas nonfunctional stay green retains leaf greenness without sustaining photosynthetic activity. Thus, functional stay-green is considered a beneficial trait that can increase grain yield in cereal crops. A stay-green japonica rice 'SNU-SG1' had a good seed setting rate and grain yield, indicating the presence of a functional stay-green genotype. SNU-SG1 was crossed with two regular cultivars to determine the inheritance mode and identify major QTLs conferring stay-green in SNU-SG1. For QTL analysis, linkage maps with 100 and 116 DNA marker loci were constructed using selective genotyping with F2 and RIL (recombinant inbred line) populations, respectively. Molecular marker-based QTL analyses with both populations revealed that the functional stay-green phenotype of SNU-SG1 is regulated by several major QTLs accounting for a large portion of the genetic variation. Three main-effect QTLs located on chromosomes 7 and 9 were detected in both populations and a number of epistatic-effect QTLs were also found. The amount of variation explained by several digenic interactions was larger than that explained by main effect QTLs. Two main-effect QTLs on chromosome 9 can be considered the target loci that most influence the functional stay-green in SNU-SG1. The functional stay-green QTLs may help develop low-input high-yielding rice cultivars by QTL marker-assisted breeding with SNU-SG1. PMID- 17846504 TI - Genome-wide examination of chromosomal aberrations in neuroblastoma SH-SY5Y cells by array-based comparative genomic hybridization. AB - Most neuroblastoma cells have chromosomal aberrations such as gains, losses, amplifications and deletions of DNA. Conventional approaches like fluorescence in situ hybridization (FISH) or metaphase comparative genomic hybridization (CGH) can detect chromosomal aberrations, but their resolution is low. In this study we used array-based comparative genomic hybridization to identify the chromosomal aberrations in human neuroblastoma SH-SY5Y cells. The DNA microarray consisting of 4000 bacterial artificial chromosome (BAC) clones was able to detect chromosomal regions with aberrations. The SH-SY5Y cells showed chromosomal gains in 1q12 approximately q44 (Chr1:142188905-246084832), 7 (over the whole chromosome), 2p25.3 approximately p16.3 (Chr2:18179-47899074), and 17q 21.32 approximately q25.3 (Chr17:42153031-78607159), while chromosomal losses detected were the distal deletion of 1p36.33 (Chr1:552910-563807), 14q21.1 approximately q21.3 (Chr14:37666271- 47282550), and 22q13.1 approximately q13.2 (Chr22:36885764 4190 7123). Except for the gain in 17q21 and the loss in 1p36, the other regions of gain or loss in SH-SY5Y cells were newly identified. PMID- 17846503 TI - Acacetin-induced apoptosis of human breast cancer MCF-7 cells involves caspase cascade, mitochondria-mediated death signaling and SAPK/JNK1/2-c-Jun activation. AB - The mechanism of acacetin-induced apoptosis of human breast cancer MCF-7 cells was investigated. Acacetin caused 50% growth inhibition (IC50) of MCF-7 cells at 26.4% 0.7% M over 24 h in the MTT assay. Apoptosis was characterized by DNA fragmentation and an increase of sub-G1 cells and involved activation of caspase 7 and PARP (poly-ADP-ribose polymerase). Maximum caspase 7 activity was observed with 100 microM acacetin for 24 h. Caspase 8 and 9 activation cascades mediated the activation of caspase 7. Acacetin caused a reduction of Bcl-2 expression leading to an increase of the Bax:Bcl-2 ratio. It also caused a loss of mitochondrial membrane potential that induced release of cytochrome c and apoptosis inducing factor (AIF) into the cytoplasm, enhancing ROS generation and subsequently resulting in apoptosis. Pretreatment of cells with N-acetylcysteine (NAC) reduced ROS generation and cell growth inhibition, and pretreatment with NAC or a caspase 8 inhibitor (Z-IETD-FMK) inhibited the acacetin-induced loss of mitochondrial membrane potential and release of cytochrome c and AIF. Stress activated protein kinase/c-Jun NH4-terminal kinase 1/2 (SAPK/ JNK1/2) and c-Jun were activated by acacetin but extracellular-regulated kinase 1/2 (Erk1/2) nor p38 mitogen-activated protein kinase (MAPK) were not. Our results show that acacetin-induced apoptosis of MCF-7 cells is mediated by caspase activation cascades, ROS generation, mitochondria-mediated cell death signaling and the SAPK/JNK1/2-c-Jun signaling pathway, activated by acacetin-induced ROS generation. PMID- 17846505 TI - Ameliorating effect of Gardenia jasminoides extract on amyloid beta peptide induced neuronal cell deficit. AB - The brains of Alzheimer's disease (AD) patients are characterized by large deposits of amyloid beta peptide (Abeta). Abeta is known to increase free radical production in nerve cells, leading to cell death that is characterized by lipid peroxidation, free radical formation, protein oxi-dation, and DNA/RNA oxidation. In this study, we selected an extract of Gardenia jasminoides by screening, and investigated its ameliorating effects on Abeta-induced oxidative stress using PC12 cells. The effects of the extract were evaluated using the 2,7 dichlorofluorescein diacetate (DCF-DA) assay and the 3-(4,5-dimethyl-thiazol-2 yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. To find the active component, the ethanol extract was partitioned with hexane, chloroform, and ethyl acetate, respectively, and the active component was purified by silica-gel column chromatography and HPLC. The results suggested that Gardenia jasminoides extract can reduce the cytotoxicity of Abeta in PC 12 cells, possibly by reducing oxidative stress. PMID- 17846506 TI - Kinetics of binding of LPS to recombinant CD14, TLR4, and MD-2 proteins. AB - TLR4 together with CD14 and MD-2 forms a pattern recognition receptor that plays an initiating role in the innate immune response to Gram-negative bacteria. Here, we employed the surface plasmon resonance technique to investigate the kinetics of binding of LPS to recombinant CD14, MD-2 and TLR4 proteins produced in insect cells. The dissociation constants (KD) of LPS for immobilized CD14 and MD-2 were 8.7 microM, and 2.3 microM, respectively. The association rate constant (Kon) of LPS for MD-2 was 5.61 x 10(3) M-1S-1, and the dissociation rate constant (Koff) was 1.28 10 2 S 1, revealing slow association and fast dissociation with an affinity constant KD of 2.33 x 10-6 M at 25 degreesC. These affinities are consistent with the current view that CD14 conveys LPS to the TLR4/MD-2 complex. PMID- 17846507 TI - Long-term expression of von Willebrand Factor by a VSV-G pseudotyped lentivirus enhances the functional activity of secreted B-Domain-deleted Coagulation Factor VIII. AB - von Willebrand factor (vWF) is a multimeric glycoprotein which functions within the coagulation system. It colocalizes with factor VIII (FVIII) by non-covalent interaction and alters its intracellular trafficking. vWF is also instrumental in maintaining the stability of secreted FVIII. The principal objective of this study was to generate a lentivirus-based vWF expression vector for gene therapy of hemophilia A. We inserted a vWF of 8.8 Kb into a lentiviral vector thereby producing VSV-G-pseudotyped vEx52. However, its titer was quite low, presumably because the length of vWF gene exceeds the size limit of the lentiviral vector. In order to overcome the low-titer, we concentrated the vEx52 and thus increased the efficiency of transduction approximately 6-fold with 1/100th of the volume. However, as concentration requires an additional laborious step, we attempted to enhance the transduction efficiency by deleting exons 24-46 and 29-46 in pRex52 to construct pRex23 and pRex28, and in pvEx52, yielding pvEx23 and pvEx28, respectively. The transfected pRex52 had a profound effect on the activity of secreted FVIII, and this activity declined as domains of vWF were deleted. However, when the domain-deleted vWF-lentiviruses were transduced into K562 cells, the vEx28 increased the activity of the secreted FVIII compared to what was observed with vEx52. This result is probably due to higher efficiencies of transduction and expression while retaining the essential domains required for proper interaction with FVIII. PMID- 17846508 TI - Marked expansion of CD11c+CD8+ T-cells in melanoma-bearing mice induced by anti-4 1BB monoclonal antibody. AB - 4-1BB (CD137), a member of the tumor necrosis factor receptor superfamily, is expressed on activated T-cells, and 4-1BB signaling due to interaction with 4-1BB ligand or ligation with anti-4-1BB monoclonal antibody (mAb) costimulates T cells. It has been shown that administration of anti-4-1BB mAb induces anti-tumor immunity in mice, but the nature of the cellular subsets responsible for this immunity is uncertain. In this study we found that anti-4-1BB mAb administration to B16F10 melanoma-bearing mice induced marked expansion of CD11c+CD8+ T-cells in parallel with suppression of pulmonary tumors. The mAb-treated mice produced higher levels of IFN- in their tumor tissues, spleen and lymph nodes than mice exposed to control antibody. When the CD11c+CD8+ T-cells were purified and re stimulated in vitro, they produced high levels of the Th1 cytokines, IFN- and IL 2, but low levels of the Th2 cytokines, IL-4 and IL-10. Furthermore, they expressed high levels of 4-1BB and CD107a, a marker of activated cytotoxic T lymphocytes. Our results suggest that CD11c+CD8+ T-cells play a role in the anti tumor immunity induced by anti-4-1BB mAb. PMID- 17846509 TI - Suppression of ADAM 10-induced Delta-1 shedding inhibits cell proliferation during the chondro-inhibitory action of TGF-beta3. AB - Although transforming growth factors (TGFs) are implicated in the process of endochondral ossification, which is initiated by the differentiation of mesenchymal cells into chondrocytes, it is not clear how TGF-beta 3 regulates the chondrogenic differentiation of limb bud mesenchymal cells. Here, differential display polymerase chain reaction (DD-PCR) screening and RT-PCR analysis revealed that transcripts of A Disintegrin And Metalloprotease 10 (ADAM 10) decreased during the chondro-inhibitory action of TGF-beta 3 on cultured chick leg bud mesenchymal cells. Electroporation of ADAM 10 morpholino antisense oligonucleotides inhibited the ectodomain shedding of delta-1, and cell proliferation and subsequent precartilage condensation, in a manner similar to that caused by TGF-beta3. The suppression of mesenchymal cell proliferation induced by TGF-beta 3 and ADAM 10 morpholino antisense oligonucleotides was reversed by activation of ADAM 10 with phorbol 12-myristate 13-acetate (PMA) or knockdown of Notch-1 with siRNA. Collectively, these data indicate that, in cultured chick leg bud mesenchyme cells, TGF-beta 3 downregulates ADAM 10 and inhibits cell proliferation and subsequent precartilage condensation by inhibiting the ectodomain shedding of delta-1, and that this results in the activation of Notch signaling. PMID- 17846510 TI - Promoter activity of the long terminal repeats of porcine endogenous retroviruses of the Korean domestic pig. AB - Porcine endogenous retroviruses (PERVs) in the pig genome represent a potential risk of infection in pig-to-human transplantation and are transmitted vertically. The solitary long terminal repeat (LTR) elements of the PERVs affect the replication properties of the individual viruses via their repeat sequences and by encoding a set of specific transcription factors. We examined the promoter activities of solitary LTR elements belonging to the PERV-A and -B families of the Korean domestic pig (KDP) using luciferase reporters. Three of the LTR structures (of PERV-A5-KDP, PERV-A7-KDP, PERV-A8-KDP) had different promoter activities in human HCT116 cells and monkey Cos7 cells, and potential negatively and positively acting regions affecting transcription were identified by deletion analysis. These data suggest that specific sequences in the U3 region of a given LTR element can affect the activities of promoter or enhancer elements in the PERV. PMID- 17846511 TI - Clinical functional magnetic resonance imaging. AB - OBJECTIVE: To describe a new series of evaluation/procedural codes that were approved by the American Medical Association (AMA) CPT Editorial Panel for use in billing for these procedures by physicians or licensed clinical psychologists. BACKGROUND: As of January of 2007, 3 distinct CPT codes for billing related to the functional magnetic resonance imaging (fMRI) procedure are available for use. DESIGN: Description of CPT codes. RESULTS: CPT code 70554: MRI, brain, fMRI; including test selection and administration of repetitive body part movement and/or visual stimulation, not requiring physician or psychologist administration. CPT code 70555: MRI, brain, fMRI; requiring physician or psychologist administration. This is to be always reported with CPT code 96020: neurofunctional testing selection and administration during noninvasive imaging functional brain mapping, with test administered entirely by a physician or psychologist, with review of test results and report. CONCLUSIONS: These CPT codes will allow for billing of both the neurofunctional and imaging components of fMRI. Functional brain mapping will now be available as an activation study to aid in localizing neurofunctional abilities. PMID- 17846512 TI - Phenylthiocarbamide (PTC) perception in Parkinson disease. AB - OBJECTIVE: To examine phenylthiocarbamide (PTC) sensitivity in Parkinson disease (PD) patients and healthy volunteers to determine whether taster status represented a simple vulnerability marker for PD. BACKGROUND: The inability to taste PTC has been associated with a number of medical illnesses not typically associated with taste impairment. Abnormalities in the function/expression of G protein-signaling pathways have been implicated in PTC perception and also in dopamine expression and regulation in PD. No study has yet probed whether PTC tasting is disrupted in PD. METHOD: PTC sensitivity was assessed in a small sample of 36 male PD patients and 20 healthy male comparison subjects using a standardized psychophysical method. RESULTS: A higher proportion of nontasters were found in patients relative to healthy comparison subjects. These differences were not explained by alterations in perception of basic taste intensity or age. Among patients, nontasters and tasters of PTC did not differ with regard to duration of illness, age of onset, severity of motor symptoms, or overall illness severity. CONCLUSIONS: These data suggest an increase in the frequency of PTC nontaster status in PD. As phenotypic variation in PTC sensitivity is genetic in origin, this may represent a surrogate risk factor for the development of PD. PMID- 17846513 TI - The genetics of very early onset Alzheimer disease. AB - OBJECTIVE: This study was undertaken to clarify the genetics of very early onset Alzheimer disease (VEOAD), defined as AD beginning before age 35. BACKGROUND: Early onset AD (EOAD) is defined by onset of symptoms before age 65, and affected individuals may harbor a mutation in presenilin 1 (PSEN1), presenilin 2 (PSEN2), or amyloid precursor protein. VEOAD is exceedingly rare, and PSEN1 mutations have been implicated. We encountered a man with phenotypic frontotemporal dementia beginning at age 32 and a strong family history of an autosomal dominant dementia who was found at autopsy to have AD. METHODS: Histologic and genetic analyses of the patient's brain were undertaken, and a review of all published VEOAD cases was performed. RESULTS: Histologic findings were diagnostic of advanced stage AD. Genetic evaluation of brain tissue identified an intronic PSEN1 polymorphism; no known pathogenic mutation was found. Literature review (1934 to 2007) disclosed 101 cases of VEOAD; the youngest age of dementia onset was 24 years. In all cases in which definitive genetic analysis was available, either a PSEN1 mutation or linkage to chromosome 14 was found. CONCLUSIONS: VEOAD can present with atypical clinical features, including findings suggestive of frontotemporal dementia. All reported cases of VEOAD with conclusive genetic analysis seem to be associated with PSEN1 mutations. Genetic testing in adults younger than 35 with dementia can identify the genetic defect and assist in diagnosis and family counseling. PMID- 17846514 TI - Multitasking disorder from right temporoparietal stroke. AB - Acute behavioral syndromes after right hemisphere stroke (eg, hemi-inattention) resolve in most patients by 6 months. Less is known about the nature of chronic disorders after these lesions when the initial deficits are no longer apparent. We report the case of a woman who suffered a cerebral infarct in the right temporoparietal region and who, after the resolution of neglect, demonstrated a significant disorder of multitasking in her everyday life. Neuropsychologic tests failed to reveal the extent of disruption in her daily functioning. A journal of daily activities elucidates the nature of her deficits and demonstrates, from the patient's perspective, the impact of the lesion on her ability to multitask. Our findings are consistent with the concept of a right frontoparietal attentional axis that governs the ability to hold several tasks in working memory at the same time. We conclude that right hemisphere lesions can disrupt the cognitive system of multitasking through disruption of the attentional matrix. PMID- 17846515 TI - Specular right-left disorientation, finger-agnosia, and asomatognosia in right hemisphere stroke. AB - OBJECTIVE: To search for specular disorders of body representations in right hemisphere stroke. BACKGROUND: Mirror self-misidentification, asomatognosia, and personal confabulation are similar to body illusions or changes in sensorial or sensorimotor perceptions generated by mirror in right brain damage patients with body image disorders. METHOD: Prospective study. Ten consecutive right-handed patients (1) performed body part naming and localization tasks and (2) were examined for asomatognosia at the acute phase of stroke, then at least 3 months after stroke, under 3 test conditions: without a mirror, with a conventional mirror, and with an inverted mirror. Video recordings of the tests were analyzed to assess performance. RESULTS: Analysis of variance of the data confirmed that the interaction of mirror's conditions (specifically without a mirror vs. an inverted mirror) with subtest type was significant. The errors are symmetrically distributed. Asomatognosia was "reactivated" in 10 patients who experienced asomatognosia during the acute phase. No particular pattern characterized the clinical manifestations of asomatognosia. CONCLUSIONS: A causal conflict of sensorial input is proposed. The specific symptoms observed would suggest the existence of an incomplete specular Gerstmann syndrome and/or Anton Babinski syndrome. These results emphasize the role of specular input in the generation of body representations and self-awareness. PMID- 17846516 TI - Oculomotor function in chronic traumatic brain injury. AB - OBJECTIVE: To characterize oculomotor function using visually guided saccade and antisaccade (AS) tasks in chronic traumatic brain injury (TBI) and assess the relationship to neuropsychologic testing. BACKGROUND: TBI causes dysfunction of prefrontal cortex, in part by disrupting cortical and subcortical pathways, resulting in specific cognitive impairments. Oculomotor function tests provide a method of assessing the integrity of these pathways. METHODS: Twenty mild TBI (MTBI), 17 moderate to severe TBI (M/STBI), and 19 healthy controls underwent oculomotor and neuropsychologic testing. RESULTS: On the visually guided saccade task, the M/STBI showed longer latencies and reduced accuracy. On the AS task, which is more dependent on prefrontal cortex function, both patient groups committed more prosaccade errors than controls. On neuropsychologic testing, only the M/STBI patients were significantly impaired. Correlations were found between AS and neuropsychologic performance. CONCLUSIONS: The M/STBI group was impaired on both oculomotor tasks and neuropsychologic testing, consistent with more global neuropathology. The MTBI group showed impaired performance primarily on the AS task, consistent with prefrontal system dysfunction. Hence, oculomotor testing is sensitive to the range of neuropathology in chronic TBI, and importantly, may be more sensitive to neuropathology in MTBI. PMID- 17846517 TI - Subclinical impairment of neuromuscular transmission in transient global amnesia. AB - OBJECTIVE: To investigate the neuromuscular transmission (NMT) of the patients with transient global amnesia (TGA) using single fiber electromyography (SFEMG). BACKGROUND: The pathophysiology of TGA remains unknown and several elements support the hypothesis of a shared background with migraine. Recent studies showed that some migraineurs have subclinical abnormalities of NMT by using SFEMG. We aimed to test the patients with TGA using SFEMG. METHODS: We investigated 6 patients diagnosed with TGA according to published criteria and 5 healthy volunteers with similar ages. SFEMG during voluntary contraction of the extensor digitorum communis muscle, nerve conduction studies and concentric needle electromyography were performed and 20 single fiber potential pairs were recorded from each subject and individual and mean jitter values were calculated. RESULTS: Three patients with TGA showed pronounced NMT failure by SFEMG, whereas none of the controls disclosed this abnormality. The mean jitter value of TGA patients (35+/-33) was greater than that of the control subjects (25+/-15) (P=0.006). Seventeen of the 120 individual jitter values of the TGA group and only 3 (from 3 different volunteers) of the 100 individual jitter values of the control group exceeded upper normal limit (P=0.004). CONCLUSIONS: These results suggest that TGA shares the same type of subclinical abnormality of NMT observed in migraine patients in recent studies. PMID- 17846519 TI - Neuropsychologic profile of a high-functioning family with a mitochondrial cytopathy. AB - OBJECTIVE: To examine the neuropsychologic profile of 3 family members diagnosed with the same mitochondrial cytopathy corresponding to a defect in the respiratory chain. BACKGROUND: The neuropsychologic functioning of patients with mitochondrial cytopathies has been largely unexamined in the literature. These mitochondrial defects often result in cell death and the failure of whole systems, including the brain. There are over 40 known types of mitochondrial cytopathies, which vary greatly in their genetic, clinical, and behavioral manifestations. METHOD: The following project describes the neuropsychologic profiles of a family (a mother and her 2 children) afflicted by the same mitochondrial cytopathy possibly associated with nucleotide 15,924. Standardized tests of premorbid intelligence estimation, attention, executive function, language, verbal and visual memory, visuospatial functioning, motor functioning, visual acuity, mood, and activities of daily living were administered. RESULTS: Participants' profiles were characterized by estimated intellectual ability in the average to superior range with marked variability on a number of assessments, making it difficult to identify a distinct pattern. General trends, however, were reflective of executive function impairment associated with dysfunction of frontal-subcortical systems. CONCLUSIONS: Mitochondrial disorders are extremely complicated and variable in their presentation. A multifactor approach should be adopted when examining neuropsychologic profiles. PMID- 17846518 TI - Relationship between self-reported apathy and executive dysfunction in nondemented patients with Parkinson disease. AB - OBJECTIVE: The prevalence of apathy was assessed across select cognitive and psychiatric variables in 32 nondemented patients with Parkinson disease (PD) and 29 demographically matched healthy control participants. BACKGROUND: Apathy is common in PD, although differentiating apathy from motor, cognitive, and/or other neuropsychiatric symptoms can be challenging. Previous studies have reported a positive relationship between apathy and cognitive impairment, particularly executive dysfunction. METHOD: Patients were categorized according to apathy symptom severity. Stringent criteria were used to exclude patients with dementia. RESULTS: Approximately 44% of patients endorsed significant levels of apathy. Those patients performed worse than patients with nonsignificant levels of apathy on select measures of verbal fluency and on a measure of verbal and nonverbal conceptualization. Further, they reported a greater number of symptoms related to depression and behavioral disturbance than did those patients with nonsignificant levels of apathy. Apathy was significantly related to self-report of depression and executive dysfunction. Performance on cognitive tasks assessing verbal fluency, working memory, and verbal abstraction and also on a self-report measure of executive dysfunction was shown to significantly predict increasing levels of apathy. CONCLUSIONS: Our findings suggest that apathy in nondemented patients with PD seems to be strongly associated with executive dysfunction. PMID- 17846520 TI - The role of stakeholders in radiation protection. PMID- 17846521 TI - The role played by stakeholders in the public debate that brought Italy out of the club of nuclear energy producers. AB - In 1964, Italy was the fourth largest world producer of electricity generated by nuclear reactors, second in Europe only to United Kingdom. In subsequent years, various controversial political events contributed towards drastically slowing down the development of the Italian national nuclear program. The 1986 Chernobyl Nuclear Power Plant accident, which caused a public outcry all over Europe, had particularly serious repercussions in Italy. In a controversial referendum, held in November 1987, Italian citizens voted to repeal three laws promoting the installation of nuclear power plants (NPP) on Italian soil and allowing the National Institute for Electrical Energy (ENEL) to participate in the construction of NPP's abroad. This work analyzes the reasons for that decision and the communication strategies of the stakeholders that took part in the public debate on nuclear energy during the weeks following the Chernobyl accident. Drawing from the methodologies used in media studies, a quantitative and qualitative analysis of two leading Italian newspapers was performed. The results reveal that a variety of stakeholders, upholding different values and interests, took part in the debate. There being no tradition of a public dialogue and participation in Italy, the debate was polarized to a "yes/no choice," which eventually caused Italy to abandon the production of nuclear power for civilian use. PMID- 17846522 TI - The calculation of dose enhancement close to platinum implants for skull radiography. AB - Materials with high atomic numbers experience the occurrence of the photoelectric effect when they are irradiated by low energy photons. A short range dose enhancement, due to the dominant photoelectric effect, close to platinum implants (Z = 78) in diagnostic radiography cannot be easily measured experimentally. The enhanced dose may increase the risk for adverse health effects from cancer or may damage vital brain structures close to the high atomic number implants. In the present work, Monte Carlo simulation using the LSCAT version of PRESTA EGS4 was employed to investigate the resulting dose enhancements. The results show that the highest estimated dose enhancement of 79% for brain tissues close to platinum implants was calculated for 65 kV x-ray energy and 180% for 120 kV x-ray energy. PMID- 17846523 TI - Effect of pigmentation density upon 2.0 microm laser irradiation thermal response. AB - Yucatan mini-pigs with predominantly dark skin have been used to determine skin safety standards for infrared (IR) wavelength irradiation due to its anatomical similarity to all human skin. It has generally been argued that water is the principle absorber in the IR-B band and melanin has relatively low absorbance. To accept dark pigmented damage thresholds for skin with various melanin densities, it is necessary to investigate the potential role of melanin in producing skin injury as characterized by an erythermal response. A Yucatan mini-pig covered with lightly pigmented pink and darkly pigmented brown skin was used in this study. The significance of skin pigmentation was investigated by comparing the transient thermal response, absorption coefficient, and the threshold damage of instant redness within 1 min and persistent redness at 48 h post exposure for dark and light skin areas at 2.0 microm wavelength. The density of melanin granules did not significantly alter the thermal and optical properties of in vivo skin exposed to 2.0 microm laser irradiation. For Gaussian shaped beam radiation at 1 s exposure duration and 4.83 mm 1/e spot diameter, the average radiant exposures at instant and persistent redness thresholds were 3.88 J cm and 5.08 J cm for dark skin, respectively, as well as 4.09 J cm and 4.09 J cm for light colored skin. Subjectively speaking, however, lightly pigmented mini-pig skin was more suitable for damage threshold estimation because of the increased contrast for visual determination of redness on light skin. PMID- 17846524 TI - Frequency spectra from current vs. magnetic flux density measurements for mobile phones and other electrical appliances. AB - The frequency spectra of electromagnetic fields have to be determined to evaluate human exposure in accordance to ICNIRP guidelines. In the literature, comparisons with magnetic field guidelines have been performed by using the frequency distribution of the current drawn from the battery. In the present study we compared the frequency spectrum in the range 217 Hz to 2.4 kHz of the magnetic flux density measured near the surface of a mobile phone with the frequency spectrum of the supply current. By using the multiple frequency rule, recommended in the ICNIRP guidelines, we estimated the magnetic field exposure in the two cases. Similar measurements and estimations were done for an electric drill, a hair dryer, and a fluorescent desk lamp. All the devices have a basic frequency of 50 Hz, and the frequency spectra were evaluated up to 550 Hz. We also mapped the magnetic field in 3D around three mobile phones. The frequency distributions obtained from the two measurement methods are not equal. The frequency content of the current leads to an overestimation of the magnetic field exposure by a factor up to 2.2 for the mobile phone. For the drill, the hair dryer, and the fluorescent lamp, the supply current signal underestimated the exposure by a factor up to 2.3. In conclusion, an accurate exposure evaluation requires the magnetic flux density spectrum of the device to be measured directly. There was no indication that the devices studied would exceed the reference levels at the working distances normally used. PMID- 17846525 TI - Variation in yearly residential radon concentrations in the upper midwest. AB - It is well known that inhalation of 222Rn and 222Rn decay products increases the risk of lung cancer. While the occurrences of high radon areas in the United States are generally known, studies examining the temporal yearly radon variation in homes across different regions are lacking. This information is essential to assess the ability of a year-long radon measurement to predict the future radon concentration in a home or reconstruct the retrospective residential radon concentration. The purpose of this study is to help fill this gap by examining the temporal variation of residential radon concentrations in homes over several years as well as to explore factors that affect the yearly temporal variability of residential radon concentrations. The coefficient of variation was used as a measure of relative variation between multiple measurements performed across homes over several years. Generalized linear model analyses were applied to investigate factors affecting the coefficient of variation. The median coefficient of variation between the first and second test period was 12%, while a median coefficient of variation of 19% was found between the first and third test period. Factors impacting the coefficients of variation were found to vary for different types of homes and by floors of a home. This study provides important insights into the uncertainty of residential radon gas concentrations that can be incorporated into the sensitivity analyses for the risk estimates of both the North American and global pooling of residential radon studies to improve risk estimates. PMID- 17846526 TI - Exposure assessment of aluminum arc welding radiation. AB - The purpose of this study is to evaluate the non-ionizing radiation (NIR) exposure, especially optical radiation levels, and potential health hazard from aluminum arc welding processes based on the American Conference of Governmental Industrial Hygienists (ACGIH) method. The irradiance from the optical radiation emissions can be calculated with various biological effective parameters [i.e., S(lambda), B(lambda), R(lambda)] for NIR hazard assessments. The aluminum arc welding processing scatters bright light with NIR emission including ultraviolet radiation (UVR), visible, and infrared spectra. The UVR effective irradiance (Eeff) has a mean value of 1,100 microW cm at 100 cm distance from the arc spot. The maximum allowance time (tmax) is 2.79 s according to the ACGIH guideline. Blue-light hazard effective irradiance (EBlue) has a mean value of 1840 microW cm (300-700 nm) at 100 cm with a tmax of 5.45 s exposure allowance. Retinal thermal hazard effective calculation shows mean values of 320 mW cm(-2) sr(-1) and 25.4 mW (cm-2) (380-875 nm) for LRetina (spectral radiance) and ERetina (spectral irradiance), respectively. From this study, the NIR measurement from welding optical radiation emissions has been established to evaluate separate types of hazards to the eye and skin simultaneously. The NIR exposure assessment can be applied to other optical emissions from industrial sources. The data from welding assessment strongly suggest employees involved in aluminum welding processing must be fitted with appropriate personal protection devices such as masks and gloves to prevent serious injuries of the skin and eyes upon intense optical exposure. PMID- 17846527 TI - Dust particle size effects on absorbed fraction values in the anterior nose. AB - The respiratory tract model introduced in Publication 66 of the International Commission on Radiological Protection (ICRP) includes consideration of extrathoracic airways, referred to as the ET region. This region comprises the anterior nose and the posterior nasal passages, larynx, pharynx, and the mouth. The deposition of inhaled particles in the airways depends on the thermal and aerodynamic properties of the particles and equations are presented to calculate the deposition efficiency in the various regions of the tract. In its dosimetric model the ICRP assumes that none of the energy emitted by the deposited source is lost in the particles itself (i.e., no self attenuation) and the deposition is assumed to be on the inner surface of the airway of the anterior nose. Therefore, the effects of various dust particle sizes on the energy deposition in the epithelium as characterized by the absorbed fraction in the anterior nose region were not addressed in ICRP 66. Since radioactive particulate matter is carried in air within dust particles, this subject should be addressed. In this paper the effects of dust particle sizes (various equivalent volume diameters) on the absorbed fraction to the anterior nose are studied using a truncated cone model for the anterior nose. The results indicate that attenuation in the dust particles has a significant effect on the electron absorbed fraction. This effect depends on the dust particle size and the energies of the electrons emitted by the radionuclides carried within dust particles. PMID- 17846528 TI - Follow up study of radiocesium contamination in a Greek forest ecosystem. AB - Radiocesiun distribution in the different parts of a Quercus conferta Kit ecosystem in Northern Greece was measured in 2005-2006, twenty years after the Chernobyl accident. The comparison between the results of this study and those previously measured (1993-1995) in the same ecosystem gives information about the long-term behavior of 137Cs in forest ecosystems. The major part of the 137Cs inventory is still in the upper layers of the soil. The radiocesium distribution in soil is fixed and has been in equilibrium at least since 1993, when the first measurements were performed. The major contamination mechanism of leaves and wood is root uptake. PMID- 17846529 TI - Fundamental uncertainties in lung counting. AB - The HML has investigated the effect the uncertainty introduced into an activity estimate from a lung count due to 1) replicate counts and 2) lung set variability. Replicate counts in the HML seem to only be affected by random statistics as the uncertainty can be predicted by Monte Carlo simulations. These findings from the lung set variability experiments suggest that a lung set has an unquantified uncertainty on its activity that adds a component to the uncertainty on the counting efficiency, and ultimately the activity estimate, as they can differ by as much as 30% at 17.5 keV or about 13% at 185.7 keV, when one is expecting only a 3% difference. PMID- 17846530 TI - Decay of environmental 137Cs. PMID- 17846531 TI - Hypothesis testing, statistical power, and confidence limits in the presence of epistemic uncertainty. PMID- 17846536 TI - Implants and the elderly. PMID- 17846537 TI - Patient financing and the implant practice. PMID- 17846538 TI - Piezoelectric distraction osteogenesis in the atrophic maxillary anterior area: a case report. AB - The reconstruction of a maxillary anterior dentoalveolar defect in patients with trauma has been a challenge for surgeons. Extensive loss of bone and teeth in the anterior maxilla presents a complex problem for reconstruction. This is owing to the difficulty in achieving complete closure using overlying soft tissue. Tension free sutures cannot be used after a large bone graft because the overlying soft tissue on severe bone defects of the anterior maxilla is often deficient and is attached to the underlying atrophic bone by scarring. Distraction osteogenesis provides a method to regain both hard tissue and soft tissue without any grafting. We describe a patient who had severe maxillary anterior bony defects that were restored by means of piezoelectric distraction osteogenesis, followed by dental implant placement. Clinical, radiological, and histological results showed that the reconstruction was successful. PMID- 17846539 TI - Immediate implant loading: current status from available literature. AB - The introduction of osseointegrated implants in dentistry represents a turning point in dental clinical practice. Thanks to their multiple therapeutic possibilities and the high predictability of success, implant therapy is now regarded as an extremely reliable approach to replace missing teeth. The concept of immediate implant loading has recently become popular due to less trauma, reduced overall treatment time, decreased patient's anxiety and discomfort, high patient acceptance and better function and esthetics. Nonetheless, research and understanding in this area are confuse and sometimes contradictory. Hence, it is the purpose of this review to provide rational for immediate implant loading, summarize current available literature, and analyze factors that influencing this newly introduced treatment method. Results from this review indicated that immediate implant loading achieved similar high success rate as that noted in the conventional approach (delayed protocols). However, a careful case selection, proper treatment plan, meticulous surgery and proper design of prosthesis are essential for optimal outcomes when this approach is adopted. PMID- 17846540 TI - Ridge expansion with acellular dermal matrix and deproteinized bovine bone: a case report. AB - Reduction of the original height and width of the alveolar bone of an edentulous site precludes optimal positioning of implant fixtures and may esthetically compromise the prosthesis. Ridge expansion at the time of extraction can prevent the need for ridge reduction and reduces the number of surgical interventions.A patient with a narrow ridge with buccal deformity was treated for the staged placement of an implant. The tooth was extracted. The socket was expanded with an osteotome and an acellular dermal matrix graft was applied as a barrier membrane. The underlying bone showed good healing with maturity and the acellular dermal matrix had the potential to increase the keratinized tissue in the extraction area. PMID- 17846541 TI - Human peri-implant bone response to turned and oxidized titanium implants inserted and retrieved after 2 months. AB - PURPOSE: The aim of this study was to evaluate the influence of oxidized surface on bone-to-implant contact percentage (BIC%) as well as the bone density within the threads area (BD%) in human bone after 2 months of unloaded healing. MATERIALS: Seven subjects (mean age 45.57 +/- 10.45 years) received 2 micro implants each during conventional implant surgery in the posterior maxilla. The implants that presented turned and oxidized surfaces served as control and test, respectively. After the healing period, the implants and the surrounding tissue were removed and prepared for ground sectioning and analysis. RESULTS: Two turned implants were found to be clinically unstable at the time of retrieval. Histometric evaluation showed that the mean of BIC% was 17.40 +/- 14.16% and 32.19 +/- 15.68% to turned and oxidized surfaces, respectively. The BD% was 22.13 +/- 19.06% for turned surface and 50.40 +/- 18.35% for oxidized surface. CONCLUSION: The histologic data from this preliminary study suggest that the oxidized micro-implants surface presented better mean values of BIC% and BD% than turned micro-implants after a short healing time. PMID- 17846542 TI - Grafting of tooth extraction socket with inorganic bovine bone or bioactive glass particles: comparative histometric study in rats. AB - PURPOSE: To compare histometrically, in rats, the bone healing after grafting the incisor extraction sockets with inorganic bovine bone or bioactive glass particles. MATERIAL: The volume fraction of grafted materials and alveolar healing components was estimated in histologic images at the end of the second and ninth weeks postoperatively by a differential point-counting method. RESULTS: Both materials were histologically observed partially filling the cervical alveolar third and, although evoking neither a foreign body reaction nor a persisting inflammatory response, delayed new bone formation in trial areas around their particles. By the second week, the delay in bone healing was more pronounced in the animals grafted with inorganic than in those grafted with bioactive glass, and an opposing result was observed during a 9-week period. CONCLUSION: Both inorganic bovine bone and bioactive glass particles grafted in the incisor extraction sockets of rats delayed new bone formation, and the degree of impairment resulted from a combination of factors such as type of material and phase of the reparation process. PMID- 17846543 TI - Influence of length and diameter of implants associated with distal extension removable partial dentures. AB - PURPOSE: The aim of this study was to evaluate the influence of the length and diameter of the implant incorporated under the saddle of a distal-extension removable partial denture, acting as support. MATERIALS AND METHODS: Six hemi mandibular models were made with the presence of left inferior cuspid and first bicuspid, with the following differences: model A, without removable partial denture; model B, removable partial denture only; model C, removable partial denture and implant of 3.75 x x mm; model D, removable partial denture and implant of 3.75 x x3 mm; model E, removable partial denture and implant of 5 x x mm; and model F, removable partial denture and implant of 5 x x3 mm. These models were designed with the aid of AutoCAD 2000 (Autodesk, Inc., San Rafael, CA) and processed for finite element analysis by ANSYS 5.4 (Swanson Analysis Systems, Houston, PA). The loads applied were 50 N vertical on each cuspid point. RESULTS: It was noted that the presence of the removable partial denture overloaded the supporting tooth and other structures. The introduction of the implant reduced tensions, mainly at the extremities of the edentulous edge. Both the length and diameter tended to reduce tensions as their dimensions increased. CONCLUSIONS: Increasing the length of the implant had a great influence on the decrease of displacement and von Mises tension values. Increasing the diameter of the implant had a great influence on the decrease of von Mises tension values, but did not influence the displacement values. According to the results of this study, it is a good choice to use the greater and larger implant possible in the association between implant and distal extension removable partial denture. PMID- 17846544 TI - Early tissue response to modified implant surfaces using back scattered imaging. AB - PURPOSE: It is now well known that implant surface properties affect osseointegration. Grit-blasting with abrasives and coating by plasma are methods to modify implant surfaces. This study aimed to compare the direction of new bone formation associated with three types of surfaces. MATERIALS AND METHODS: Titanium (Ti) alloy rods grit-blasted with alumina abrasive (Group 1, G1), with apatitic abrasive (Group 2, G2), and with apatitic abrasive and plasma-sprayed with hydroxyapatite (Group 3, G3) were implanted in surgically created defects in tibias of New Zealand white rabbits for 2 and 4 weeks. After sacrifice, the implants and surrounding bones were obtained and analyzed using back scattered imaging. RESULTS: Differences in patterns of bone formation among the groups were observed: originating from the cortical bone towards the implant surface (Type A), surrounding the implant (Type B) and originating from the medullary cavity (Type C). G1 and G3 showed Types A and B while G2 exhibited Types A, B and C. After 4 weeks, greater amount of new bone was observed in G2 group compared with those in G1 and G3 groups. CONCLUSIONS: This study demonstrated that patterns of bone formation are influenced by methods of surface modification. PMID- 17846545 TI - Histomorphometric analyses of bone interface with titanium-aluminum-vanadium and hydroxyapatite-coated implants by biomimetic process. AB - PURPOSE: The surface properties of dental implants have been considered directly related to the success of the osseointegrated interface. Hydroxyapatite (HA) coated implants promote a bioactive surface because they facilitate cellular migration and bone growth, resulting in a faster osseointegration. MATERIALS AND METHODS: This study analyzed and compared 2 different implant surfaces: a group composed of titanium implants and another group coated with HA. The HA coating was produced by the biomimetic process to reduce costs. RESULTS AND CONCLUSIONS: After histomorphometric analyses it was possible to demonstrate that there were no statistically significant differences between the groups. PMID- 17846546 TI - Hydroxyapatite-electroplated cp-titanium implant and its bone integration potentiality: an in vivo study. AB - PURPOSE: This study was designed to precipitate hydroxyapatite coating on the surface of commercially pure titanium (cpTi) implants using an electroplating technique. After characterization of the hydroxyapatite coating, the bone-implant interface and bone integration of both cpTi and hydroxyapatite-coated implants were assessed. MATERIALS: Twenty implants were divided equally into 2 main groups (n = 10). Ten cpTi implants were utilized as received, while the others were hydroxyapatite coated and then sterilized. The implants of both groups were inserted in the tibiae of New Zealand rabbits. The purity and crystallinity of the hydroxyapatite coat were characterized using x-ray diffraction. A scanning electron microscope examined the grain morphology. Profilometer evaluated the surface texture before and after sterilization. Histological examination using a scanning electron microscope was performed to qualify osseointegration of the regenerated bone and measure the gap distance at the bone-implant interface. RESULTS: Pure crystalline hydroxyapatite precipitate of thickness (range 69-78 microm) and rough surface (2.7 +/- 0.2 microm) compared to smooth cpTi (1.3 +/- 0.5 microm). The gamma-radiation sterilization resulted in finer grains and insignificant smoother surface. Histological examination of the cpTi implant exhibited less bone regeneration with few and less dense bone trabeculae, and gap distance was significantly high (1.29 +/- 0.51 microm). Meanwhile, the hydroxyapatite-coated implant showed a recognizable amount of bone regeneration with more and denser bone trabeculae, and gap distance ranged from 0 to 1.32 microm. CONCLUSIONS: The employed technique provided a thin and uniform pure crystalline hydroxyapatite coating. The characterization of the precipitated film is promising for clinically successful long-term bone fixation. PMID- 17846547 TI - Effect on the amount of bone-implant contact when splinting immediate-loaded dental implants. AB - PURPOSE: Much attention has been focused on the immediate or early loading of implants with or without splinting. The purpose of this study was to evaluate the contact rate between bones and implants, with or without splinting. MATERIALS AND METHODS: Under general anesthesia, an 8-mm-deep cavity for a dental implant was drilled in the mandibular ridge of dogs where teeth had been extracted 4 months earlier. Rough-surfaced, cylindrical screw implants (International Team for Implantology [ITI] monotype implants 4 mm diameter and 8 mm long, Straumann, Basel, Switzerland) were placed with splinting on the right side and without splinting on the left side using gold abutment. Resin plates for the maxilla were adjusted to attach to the gold abutment in each mandible. At 4, 8, or 12 weeks after the implantation, specimens were stained using toluidine blue and fuchsin. The sections were observed and morphometric analysis was performed to measure the rates of bone-implant contact and new bone-implant contact. RESULTS: The ratio of bone-implant contact on the lingual side was higher than on the buccal side in both the splinted and the unsplinted groups, and the rates in the splinted group were also higher than in the unsplinted group. The ratio of new bone-implant contact was not significantly different between the splinted and unsplinted groups, except for spongy bone at 4 weeks. CONCLUSION: Splinting of immediate loading dental implants can be adequate for osseointegration, particularly in spongy bone. PMID- 17846548 TI - Microvessel density in sinus augmentation procedures using anorganic bovine bone and autologous bone: 3 months results. AB - PURPOSE: This study was an immunohistochemical evaluation of microvessel density (MVD) in sinus augmentation procedures with autologous bone and anorganic bone (Bio-Oss). MATERIALS AND METHODS: Twenty-four patients (14 men and 10 women - mean age of 48 years with a range from 34 to 53 years) participated in this study. All the patients presented a maxillary partial unilateral edentulism involving the premolar/molar areas, with a residual alveolar ridge height of about 4 to 5 mm. Twelve patients received sinus augmentation procedures with 100% autologous bone; 100% Bio-Oss was used in the other 12 patients. Endosseous implants were inserted after a mean period of 3 months. As control, the portions of preexisting subantral bone were used. The mean value of the MVD in control bone was 23.4 +/- 1.3. The mean value of the MVD in the sinuses augmented with autologous bone was 29.0 +/- 2.4. The mean value of the MVD in the sinuses augmented with Bio-Oss was 23.8 +/- 2.2. RESULTS: The statistical analysis showed that the differences of the MVD between control bone and sinuses augmented with Bio-Oss were not statistically significant (P = 0.52), while the difference of the MVD between sinuses augmented with autologous bone and those augmented with Bio-Oss was statistically significant (P = 0.0008). CONCLUSIONS: Autologous bone may act not only as a passive filling material in bone defects but may also release osteogenic growth factors; and particles of autologous bone seem to contain vital osteoprogenitor cells. PMID- 17846550 TI - Gender and ethnic differences in cancer pain experience: a multiethnic survey in the United States. AB - BACKGROUND: Inconsistent findings on ethnic differences in cancer pain experience suggest the need for further studies on this topic for adequate cancer pain management. OBJECTIVES: To determine ethnic differences in cancer pain experience of four ethnic groups in the United States. METHODS: A feminist perspective was used as the theoretical basis. This was a survey of a multiethnic sample of 480 cancer patients asking questions on sociodemographic characteristics and health or illness status, 3 unidimensional cancer pain scales, 2 multidimensional cancer pain scales, the Memorial Symptom Assessment Scale, and the Functional Assessment of Cancer Therapy Scale. The data were analyzed using descriptive and inferential statistics including ANOVA and hierarchical multiple regression analyses. RESULTS: The results indicated certain ethnic differences in types of pain and symptoms that patients experienced. Also, the results demonstrated significant ethnic differences in cancer pain and functional status. DISCUSSION: The findings suggest further in-depth qualitative exploration on cultural values and beliefs related to cancer pain in each ethnic group and national studies with a larger number of ethnic minorities on this topic. PMID- 17846551 TI - Multiple factors related to bottle-feeding performance in preterm infants. AB - BACKGROUND: A great deal of attention has focused on understanding preterm infant feeding behaviors and on strategies to support the preterm infant during this period; however, comprehensive descriptions of the feeding behavior of preterm infants that incorporate an examination of multiple subsystem levels are lacking. OBJECTIVE: To examine various physical indicators related to preterm infants' bottle-feeding performance. METHODS: This was a retrospective, descriptive, exploratory study using a convenience sample. Medical records of 116 preterm infants were reviewed from the initiation of bottle-feeding until discharge from the neonatal intensive care unit. This study examined bottle-feeding performance (volume intake in milliliters per minute) as well as postmenstrual age, weight at each observed feed, oral motor skills, signs of distress, feeding techniques, feeding experience, gender, and Apgar scores at 5 minutes. Oral motor skills were measured by the Neonatal Oral Motor Assessment Scale. RESULTS: Linear mixed effects models were used to examine the relationship between bottle-feeding performance and the remaining variables. Postmenstrual age, weight at each observed feed, oral motor skills, feeding experience, and feeding techniques were found to be significant predictors of feeding performance at the .05 level. CONCLUSIONS: Multiple factors, both intrinsic and extrinsic, play a role in determining an infant's bottle-feeding performance. In addition to age and weight, the presently employed conventional criteria, oral motor skills, feeding practice, and feeding techniques also contribute to infants' feeding performance. Arbitrary age (34 weeks gestational age) and weight criteria (1,500 g) should not be the only indicators for oral feeding. PMID- 17846552 TI - Effects of nurse-managed telemonitoring on blood pressure at 12-month follow-up among urban African Americans. AB - BACKGROUND: Nearly one in three adults in the United States has hypertension. Hypertension is one of the largest risk factors for cardiovascular diseases, and it is growing in prevalence, especially among African Americans. OBJECTIVES: To test the hypothesis that individuals who participate in usual care (UC) plus blood pressure (BP) telemonitoring (TM) will have a greater reduction in BP from baseline to 12-month follow-up than would individuals who receive UC only. METHODS: A two-group, experimental, longitudinal design with block stratified randomization for antihypertensive medication use was used. African Americans with hypertension were recruited through free BP screenings offered in the community. Data were collected through a structured interview and brief physical exam. Cross tabs, repeated measures analysis of variance, and independent t tests were used to analyze the study's hypothesis. RESULTS: The TM intervention group had a greater reduction in systolic BP (13.0 mm Hg) than the enhanced UC group (7.5 mm Hg; t = -2.09, p = .04) from baseline to the 12-month follow-up. Although the TM intervention group had a greater reduction in diastolic BP (6.3 mm Hg) compared with the enhanced UC group (4.1 mm Hg), the differences were not statistically significant (t = -1.56, p = .12). DISCUSSION: : Telemonitoring of BP resulted in clinically and statistically significant reductions in systolic BP over a 12-month period; if maintained over a longer period of time, the reductions could improve care and outcomes significantly for African Americans with hypertension. PMID- 17846553 TI - Background noise: the experience of chemotherapy-induced peripheral neuropathy. AB - BACKGROUND: A substantial portion of the 1.3 million persons diagnosed annually with cancer receive neurotoxic chemotherapy that may produce distressful symptoms and changes in functional ability. However, little is known about the symptom experience and daily life effects of chemotherapy-induced peripheral neuropathy (CIPN). OBJECTIVE: To describe the CIPN symptom experience and the influence of symptoms on everyday life. METHODS: This was a qualitative, exploratory, interpretive, descriptive study with semistructured interviews. A purposive sample of 28 participants was recruited from a rural National Cancer Institute designated comprehensive cancer center. Interviews were audiotaped, transcribed verbatim, and imported into Atlas.ti software. Content analysis and constant comparative method were used to analyze the data. RESULTS: Participants represented diversity in age (46-81 years), cancer type, time since diagnosis (3 198 months), neuropathy severity, and neurotoxic chemotherapy agents received. Content analysis yielded a rich, thick description of CIPN symptoms and the influence of the symptoms on functional ability and everyday life. Further interpretive analysis provided a description of the symptom experience through an overarching metaphor, Background Noise, and four major themes: (a) Becoming Aware; (b) Learning New Lyrics; (c) Functional, Emotional, and Social Role Cacophony; and (d) Learning to Live With It. Participants described significant physical limitations, emotional distress, and social role impairments due to CIPN. CONCLUSIONS: Having CIPN results in diverse symptom patterns and degrees of physical symptom distress from mild to severe, emotional distress, alterations in functional ability, and social role impairment. Comprehensive clinical and research measures are needed to assess the full spectrum of CIPN effects on everyday life. PMID- 17846554 TI - A single-item approach to screening elders for oral health assessment. AB - BACKGROUND: Oral health contributes significantly to overall health. Finding a single item that can be used by primary care providers to screen elders who are in need of oral care is important. OBJECTIVES: The objective of this article was to evaluate usefulness of the item: "Do you have regular dental checkups?" as a means to decide whether an oral health assessment or further referral is indicated. Answering no is postulated as a positive predictor of poor oral health and need for care. METHODS: This study was a secondary analysis of a nutritional survey of 240 community-dwelling elders. Examiner-rated Kayser-Jones Brief Oral Health Status Examination; self-reported General Oral Health Assessment Index; number of remaining teeth; and pattern of checkups (regular vs. irregular) were evaluated by a trained gerontological nurse practitioner during an in-home assessment. RESULTS: A dental visit within the past year for any reason was reported by 132 subjects (55.0%), but only 81 (33.8%) reported some sort of regular dental checkups. For dentate elders (n = 147), an irregular checkup was associated with lower educational level, Protestant faith, and Black race. People with irregular checkups scored significantly lower on all three oral indices. The negative predictive values and likelihood ratio negative values ranged 98.7 100.0% and 0.00-0.98, respectively, indicating that this item of interest is valid for ruling-out dentate subjects with good oral health. For edentulous elders (n = 93), the item was less effective. DISCUSSION: A single item, "Do you have regular dental checkups?" can be used effectively to rule out dentate elders with good oral health and identify those who are in need of further oral health assessment or referrals. PMID- 17846555 TI - Factor structure of the geriatric care environment scale. AB - BACKGROUND: Older adults comprise approximately 60% of all adult, nonobstetric hospital admissions. Nurses Improving Care for Health System Elders (NICHE) is a national program aimed at system improvement to achieve patient-centered care for older adults. The NICHE hospitals use the Geriatric Institutional Assessment Profile (GIAP) to assess their institutional readiness to provide quality care to older adults and to document improvement in geriatric care delivery. OBJECTIVE: To explore the factorial structure of the 28-item Geriatric Care Environment Scale (GCES) of the GIAP, test its validity with a sample of staff registered nurses (RNs), and evaluate its invariance across 4 groups of RNs who worked at 4 different types of hospitals. METHODS: Staff RNs (N = 9,400) at 71 acute hospitals, who responded to the GIAP from 1999 to 2004, were split randomly into 2 groups for cross-validation. A 3-step data analysis was completed. The a priori factor structure was developed using exploratory factor analysis. The obtained factor model was validated, and its invariance by types of hospitals was examined by confirmatory factor analyses. RESULTS: The GCES is internally consistent (Cronbach's alpha = .93) and accounts for approximately 55% of the total variance. The 4 factors extracted from the exploratory factor analysis are Aging Sensitive Care Delivery, Resource Availability, Institutional Values Regarding Older Adults and Staff, and Capacity for Collaboration. The 4-factor structured model is validated in a half-randomly selected sample (normed fit index [NFI] = .931, nonnormed fit index [NNFI] = .933, comparative fit index [CFI] = .939, root mean-square error of approximation [RMSEA] = .058) and does not vary significantly across the 4 groups of RNs who worked at the 4 different types of hospitals (NFI = .969, NNFI = .975, CFI = .976, RMSEA = .027). CONCLUSIONS: The GCES is a reliable measure of RN perception of how care provided to older adults reflects age-sensitive principles and the organizational practice environment that supports or hinders care delivery. PMID- 17846556 TI - Translation and validation of a chinese version of the parenting sense of competence scale in chinese mothers. AB - BACKGROUND: Women's sense of competence and satisfaction in the maternal role are essential for positive parenting practices and child development. Measures of maternal role competence and satisfaction are limited in the Chinese population. OBJECTIVES: To translate the Parenting Sense of Competence Scale into Chinese (C PSOC) and to examine the psychometric properties of the C-PSOC. METHODS: A cross sectional survey was conducted using a convenience sample of 170 mothers recruited from a postnatal unit. Participants completed the C-PSOC, Rosenberg's Self-Esteem Scale, and the Edinburgh Postnatal Depression Scale. A randomly selected subsample of 57 mothers participated in the 4-week retest. RESULTS: The C-PSOC demonstrated good internal consistency (Cronbach's alpha = .85) and test retest reliability (intraclass correlation coefficient = .87). Factor analysis supported the two-factor structure reflecting the efficacy and satisfaction dimensions of the original instrument. The scale discriminated between primiparas and multiparas (t = 2.2, p < .05). Significant correlations with Rosenberg's Self Esteem Scale (r = .60, p < .01) and the Edinburgh Postnatal Depression Scale (r = -.48, p < .01) demonstrated good construct validity. CONCLUSION: The C-PSOC has satisfactory psychometric properties. It has the potential to be used as a clinical and research instrument for measuring maternal role competence and satisfaction in the Chinese population. PMID- 17846557 TI - Intraclass correlations among physiologic measures in children and adolescents. AB - BACKGROUND: Cluster designs have become increasingly popular in many research areas. Adopting these designs requires special considerations because individuals within the same cluster may be correlated. Therefore, appropriate sample size calculations in these settings require the incorporation of additional information regarding intraclass or intracluster correlations (ICCs), which measure the degree of similarity between individuals within the same cluster or class. OBJECTIVES: To discuss the importance of the ICC in cluster-designed studies and present ICC estimates for selected physiologic characteristics in children and adolescents. METHOD: The ICCs for body mass index (BMI), sum of skinfolds (SSF), blood pressure, glucose, insulin, and lipids were determined using baseline data from the Cardiovascular Health in Children and Youth Studies (CHIC II and III). The ICC estimates presented were obtained through the use of mixed models for the entire data set and separately by age groups, gender, and ethnicity. RESULTS: The estimated ICCs ranged from .0104 for BMI to .1657 for glucose. The differences in the estimated ICCs among the three age groups were most marked for blood pressure, SSF, and glucose and were small for aerobic power, insulin, and lipids. The greatest difference in ICC by gender was in BMI and SSF: The ICC for SSF in girls was 8.2 times larger than that for boys. Caucasians had higher ICC estimates for insulin than did African Americans and other ethnic groups. DISCUSSION: The magnitude of the ICC varied by the outcome of interest, and factors such as age, gender, and ethnicity also influenced the magnitude of the ICC. The presence of ICCs should be assumed when using cluster designs, and ICCs should be considered when conducting sample size calculations for such studies. PMID- 17846558 TI - Determining content validity of a self-report instrument for adolescents using a heterogeneous expert panel. AB - BACKGROUND: The use of experiential experts, especially children and adolescents, in content validity evaluations of new instruments has not been described well. OBJECTIVE: To describe the use of experiential experts in a content validity evaluation of a new instrument. METHODS: Experiential (adolescents and parents, n = 11) and professional (diabetes clinicians and researchers, n = 17) expert judges evaluated the content validity of a new instrument that measures self management of Type 1 diabetes in adolescents. The content validity index for each of 99 items (I-CVIs) for the total group of experts (n = 28; I-CVI-ALL) and for the experiential experts only (I-CVI-EXPERIENTIAL) were calculated, respectively, and both were used to inform decisions about whether to retain, eliminate, or revise each item. RESULTS: There were 20 items where the I-CVI-ALL was >/=.80 and the I-CVI-EXPERIENTIAL was <.80. Each of these 20 items was evaluated critically. Some were retained (n = 3), some were eliminated (n = 7), and some were revised as suggested by the experts (n = 10). DISCUSSION: Using experiential content validity experts (adolescents and parents) and critically evaluating their recommendations regarding items can result in further elimination and revision of items beyond what is suggested by content validity assessment done by professional experts. The result may be a more thorough content validity assessment of the instrument, leading to an instrument with greater relevance for the target population. PMID- 17846559 TI - Low sensitivity of total lymphocyte count as a surrogate marker to identify antepartum and postpartum Indian women who require antiretroviral therapy. AB - BACKGROUND: Some studies support the use of total lymphocyte count (TLC) as a surrogate marker for CD4 cell count to guide antiretroviral therapy (ART) initiation. However, most of these studies have focused on nonpregnant adults. In light of expanding ART access through prevention of mother-to-child transmission (PMTCT)-plus programs in resource-limited settings, we assessed the sensitivity, specificity, and positive predictive value (PPV) of TLC for predicting low CD4 counts in antepartum and postpartum women in Pune, India. METHODS: CD4, TLC, and hemoglobin were measured at third trimester, delivery, and 6, 9, and 12 months postpartum (PP) in a cohort of 779 HIV-infected women. Optimal TLC cutoff for predicting CD4 <200 cells/mm3 was determined via logistic regression where sensitivity, specificity, PPV, and an area under the receiver operating characteristic (ROC) curve were calculated. RESULTS: Among the 779 women enrolled, 16% had WHO clinical stage 2 or higher and 7.9% had CD4 <200 cells/mm3. Using 2689 TLC-CD4 pairs, the sensitivity, specificity, and PPV of TLC <1200 cells/mm3 for predicting CD4 <200 cells/mm3 was 59%, 94%, and 47%, respectively. The sensitivity of TLC <1200 cells/mm3 cutoff ranged between 57% and 62% for time points evaluated. Addition of hemoglobin <12 g/dL or <11 g/dL increased the sensitivity of TLC to 74% to 92% for predicting CD4 <200 cells/mm3 but decreased the specificity to 33% to 69% compared to TLC alone. A combination of TLC, hemoglobin, and WHO clinical staging had the highest sensitivity but lowest specificity compared to other possible combinations or use of TLC alone. The sensitivity and specificity of TLC <1200 cells/mm3 to predict a CD4 <350 cells/mm3 was 31% and 99%, respectively. CONCLUSIONS: Our data suggest that antepartum and PP women with TLC <1200 cells/mm3 are likely to have CD4 <200 cells/mm3. However, the sensitivity of this TLC cutoff was low. Between 45% and 64% of antepartum and PP women requiring initiation of ART may not be identified by using TLC alone as a surrogate marker for CD4 <200 cells/mm3. The WHO recommended TLC cutoff of <1200 cells/mm3 is not optimal for identifying antepartum and PP Indian women who require ART. PMID- 17846560 TI - HIV/AIDS-specific quality of life and adherence to antiretroviral therapy over time. AB - OBJECTIVE: To determine if HIV/AIDS-specific quality of life (QOL) predicts adherence to antiretroviral therapy (ART). METHODS: HIV-infected outpatients on efavirenz plus 2 or 3 nucleoside analogue reverse transcriptase inhibitors and with HIV viral loads <75 copies/mL were followed until the censoring event of detectable viremia or 1 year of follow-up. QOL was assessed at baseline with the HIV/AIDS-Targeted Quality of Life instrument (HAT-QoL), as were depression symptoms, stress levels, social support, and substance use. Follow-up high (> or =95%) versus low (<95%) adherence was measured for 90 days before the censoring event. RESULTS: Fifty-six (48%) of 116 recruited participants had low adherence. Baseline financial worries (from the HAT-QoL) were greater in those with low versus high adherence (P = 0.02). Those with low versus high adherence also were more likely to use alcohol (P = 0.01) and other drugs (P = 0.02) currently at baseline. Regression analysis led to a model that included only current alcohol use (odds ratio [OR] = 2.65, 95% confidence interval [CI]: 1.20 to 5.87)) and financial worries (OR = 1.16, 95% CI: 1.03 to 1.310, for each 10-unit rise). CONCLUSIONS: Baseline financial worries were associated with antiretroviral adherence later in time. Questions about paying bills and financial ability to care for oneself may be clinically useful in identifying patients who will have suboptimal adherence. PMID- 17846561 TI - Racial disparities in HIV incidence among young men who have sex with men: the Baltimore Young Men's Survey. AB - Recent reports have demonstrated racial disparities in the prevalence of HIV infection among men who have sex with men (MSM). The objectives of this study are to investigate whether racial disparities exist in HIV incidence among young MSM in Baltimore, MD and to examine potential explanations for differences. Data were collected by the Baltimore Young Men's Survey, a cross-sectional venue-based survey (1996 to 2000) enrolling MSM aged 15 to 29 years. HIV incidence was ascertained using the serologic testing algorithm for recent HIV seroconversion. HIV incidence was 4.2% per year (95% confidence interval [CI]: 1.2 to 10.5) among 843 participants. There were substantial racial differences in HIV incidence, ranging from 0 among Hispanics to 11.0% per year (95% CI: 5.5 to 19.7) among non Hispanic blacks. In multivariate analysis, among MSM at risk for HIV acquisition, race was not associated with unprotected anal intercourse. Independent risks included having more than 4 recent male sexual partners (adjusted odds ratio [AOR] = 1.6, 95% CI: 1.0 to 2.4) and being under the influence of drugs while having sex (AOR = 1.6, 95% CI: 1.1 to 2.3). Non-Hispanic blacks were no more likely than non-Hispanic whites to report these risk behaviors. Possible alternative explanations for the observed racial disparities in HIV incidence and implications for prevention are explored. PMID- 17846562 TI - Radical-scavenging activity of natural methoxyphenols vs. synthetic ones using the induction period method. AB - The radical-scavenging activities of the synthetic antioxidants 2-allyl-4-X phenol (X = NO2, Cl, Br, OCH3, COCH3, CH3, t-(CH3)3, C6H5) and 2,4 dimethoxyphenol, and the natural antioxidants eugenol and isoeugenol, were investigated using differential scanning calorimetry (DSC) by measuring their anti-1,1-diphenyl-2-picrylhydrazyl (DPPH) radical activity and the induction period for polymerization of methyl methacrylate (MMA) initiated by thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN) and benzoyl peroxide (BPO). 2 Allyl-4-methoxyphenol and 2,4-dimethoxy-phenol scavenged not only oxygen-centered radicals (PhCOO*) derived from BPO, but also carbon-centered radicals (R*) derived from the AIBN and DPPH radical much more efficiently, in comparison with eugenol and isoeugenol. 2-Allyl-4-methoxyphenol may be useful for its lower prooxidative activity. PMID- 17846563 TI - Antibacterial activity of long-chain fatty alcohols against Staphylococcus aureus. AB - The antibacterial activity against Staphylococcus aureus of long-chain fatty alcohols was investigated, with a focus on normal alcohols. The antibacterial activity varied with the length of the aliphatic carbon chain and not with the water/octanol partition coefficient. 1-Nonanol, 1-decanol and 1-undecanol had bactericidal activity and membrane-damaging activity. 1-Dodecanol and 1 tridecanol had the highest antibacterial activity among the long-chain fatty alcohols tested, but had no membrane-damaging activity. Consequently, it appears that not only the antibacterial activity but also the mode of action of long chain fatty alcohols might be determined by the length of the aliphatic carbon chain. PMID- 17846564 TI - Comparative chemical analysis of the essential oil constituents in the bark, heartwood and fruits of Cryptocarya massoy (Oken) Kosterm. (Lauraceae) from Papua New Guinea. AB - Exhaustive hydro-distillation of the bark, heartwood and fruits of Cryptocarya massoy (Lauraceae) afforded pale yellow-coloured oils in 0.7, 1.2 and 1.0 % yields, respectively. Detailed chemical evaluation of these distillates using GC/MS revealed the major components in the bark and the heartwood oils to be the C-10 (5,6-dihydro-6-pentyl-2H-pyran-2-one) and C-12 (5,6-dihydro-6-heptyl-2H pyran-2-one) massoia lactones, while the major fruit oil constituent was benzyl benzoate (68.3 %). The heartwood also contained trace amounts of the C-14 (5,6 dihydro-6-nonyl-2H-pyran-2-one) massoia lactone (1.4 %) and the saturated C-10 derivative delta-decalactone (2.5 %). PMID- 17846565 TI - Isatinones A and B, new antifungal oxindole alkaloids from Isatis costata. AB - Two new oxindole alkaloids isatinone A (1) and B (2) have been isolated from Isatis costata, along with the known trisindoline. Their structures have been assigned on the basis of spectroscopic techniques and chemical studies. Both new compounds showed significant antifungal activity. PMID- 17846566 TI - One pot synthesis of alpha-aminophosphonates containing bromo and 3,4,5 trimethoxybenzyl groups under solvent-free conditions. AB - New alpha-aminophosphonates were synthesized by the Kabachnik-Fields reaction of 3,4,5-trimethoxybenzaldehyde (TMB) with p- or m-bromoaniline and a dialkyl phosphite under solvent-free conditions. TMB was prepared from gallic acid via a four step synthetic sequence involving etherification, esterification, hydrazidation and potassium ferricyanide oxidation. The structures of all synthesized compounds were confirmed by elemental analysis, IR, 1H-, 13C- and 31P NMR spectral data. Compound 7g was also characterized by X-ray crystallography. A half-leaf method was used to determine the in vivo curative efficacy of the eight title products against tobacco mosaic virus (TMV). It was found that compounds 7g and 7h possess good in vivo curative effects against TMV. PMID- 17846567 TI - Synthesis, NMR and crystallographic studies of 2-substituted dihydroquinazolinones derived from (S)-phenylethylamine. AB - 2,3-Dihydro-3-[(S)-1-phenethyl]quinazolinone and some new 2-substituted derivatives bearing isopropyl, o-nitrophenyl and p-nitrophenyl groups were prepared in 40-90% yield by amidation of isatoic anhydride with (S) phenylethylamine, followed by condensation with triethyl orthoformate, isopropylaldehyde, o-nitro- and p-nitro-benzaldehyde, respectively. The two 2 subtituted dihydroquinazolinones obtained either by using isopropylaldehyde, o nitro- or p-nitrobenzaldehyde, were separated and purified before their NMR spectra in CDCl3 solutions were recorded. The detection of the low energy conformation of O=C-N-phenethyl segment in solution allowed the correlation of the NMR data with the configuration of newly stereogenic carbon C-2; thus, one diastereomer was labeled SS while the other was RS. Configurations determined by the NMR method were corroborated by X-ray diffraction analysis. X-ray structures of each diastereomeric series showed characteristic conformational types: a propeller-like for the SS and a hairpin for the RS series. Interatomic distances of the hairpin conformation suggest the existence of intramolecular face-to-face interactions between two aromatic rings. PMID- 17846568 TI - Synthesis of 3,4,7,8-tetrahydronaphthalene-1,5(2H,6H)-dione. AB - A short and high yielding route for the preparation of the title compound, starting from commercially available 1,5-dihydroxynaphthalene, is described. The key step in the sequence is the air oxidation of a bis(trimethylsilyloxy)diene precursor. PMID- 17846569 TI - Synthesis and photochemistry of 1-iodocyclohexene: influence of ultrasound on ionic vs. radical behaviour. AB - Simultaneous application of UV light and ultrasonic irradiation to a reaction mixture containing 1-iodocyclohexene is reported. The irradiation of 1 iodocyclohexene in methanol was carried out with or without addition of zinc. The effect of ultrasound or mechanical stirring on this solid-liquid system was also compared. The irradiation of 1-iodocyclohexene in methanol in the presence of zinc increases the yield of the nucleophilic trapping product, compared with the yield after irradiation in the absence of zinc. The photodegradation of 1 iodocyclohexene was slightly accelerated after addition of zinc. A rapid formation of radical product was accompanied by substantial decrease of 1 iodocyclohexene after application of ultrasound and irradiation without the zinc. The ultrasound significantly affects the photobehaviour of this reaction, predominantly its radical route. The joint application of ultrasound and zinc contributes positively to the production of radical and ionic products. The sonochemical stirring is more effective than mechanical stirring. PMID- 17846570 TI - Synthesis of 2,5-disubstituted octahydroquinolin-4-ones via anintramolecular hetero Diels-Alder reaction. AB - A route for the preparation of 2,5-disubstituted octahydroquinolin-4-ones, synthetic precursors of the decahydroquinoline-type toxins, is presented. The key steps are an asymmetric epoxidation and an intramolecular hetero Diels-Alder reaction between an activated diene and an imine. The presence of an allylic stereogenic center induces some selectivity and thus only two cycloadducts are obtained in 70:30 ratio and good yield. PMID- 17846571 TI - A novel antioxidant phenyl disaccharide from Populus tremula knotwood. AB - The complete characterization of two compounds obtained from the acetone extract of Populus tremula knotwood has been was achieved using LC-DAD-MS, MS/MS, IR and NMR. The new compounds were unequivocally identified as a mixture of the ester isomers of the (E) and (Z) p-coumarate of 1-O-rutinose. The isomers showed the capacity to inhibit lipid peroxidation induced by tert-butylhydroperoxide and to trap peroxyl radicals, as determined by a chemiluminescence method. These new phenyl disaccharides also showed a significant ORAC (oxygen radical absorbance capacity) value, i.e. 11.7 microM TE (Trolox Equivalents). PMID- 17846572 TI - Novel 2-chloro-8-arylthiomethyldipyridodiazepinone derivatives with activity against HIV-1 reverse transcriptase. AB - Based on the molecular modeling analysis against Y181C HIV-1 RT, dipyridodiazepinone derivatives containing an unsubstituted lactam nitrogen and 2 chloro-8-arylthiomethyl were synthesized via an efficient route. Some of them were evaluated for their antiviral activity against HIV-1 RT subtype E and were found to exhibit virustatic activity comparable to some clinically used therapeutic agents. PMID- 17846573 TI - Efficient preparation of aldoximes from arylaldehydes, ethylenediamine and Oxone in water. AB - The one-pot reaction of aromatic aldehydes, ethylenediamine and Oxone (2 KHSO5 x KHSO4 x K2SO4) in pure water was found to unexpectedly afford aldoximes in excellent yields. PMID- 17846574 TI - Asymmetric synthesis of the epimeric (3S)-3-((E)-hex-1-enyl)-2 methylcyclohexanones. AB - The asymmetric rhodium-catalysed 1,4-addition of alkenylzirconium reagents to 2 cyclohexenone can be useful in the synthesis of 3-alkenyl-2-methylcyclohexanones, provided that formaldehyde is used in trapping the intermediate zirconium enolates. In this manner a four-step sequence leading to the two epimeric 3 hexenyl-2-methylcyclohexanones in enantiomeric form was developed. PMID- 17846575 TI - Synthesis, characterization and antibacterial activity of azomethine derivatives derived from 2-formylphenoxyacetic acid. AB - A series of eight new azomethine derivatives were synthesized by reacting 2 formylphenoxyacetic acid with aromatic amines. The chemical structures of these compounds were confirmed by means of 1H-NMR, 13C-NMR, MS and elemental analysis. The compounds were assayed by the disc diffusion method for antibacterial against Staphylococcus aureus and Escherichia coli. Among the compounds tested, 2a, 2b, 2e, 2g and 2h exhibited good antibacterial activity, almost equal to that of Ciprofloxacin used as standard. PMID- 17846576 TI - Heteropolyacids as green and reusable catalysts for the synthesis of 3,1,5 benzoxadiazepines. AB - Synthesis of 3,1,5-benzoxadiazepines from the condensation of o-phenylenediamine (o-PDA) and acyl chlorides in the presence of a catalytic amount of various heteropolyacids (HPAs) is reported. PMID- 17846577 TI - Reactive oxygen species scavenging activity of flavone glycosides from Melilotus neapolitana. AB - One new and six known flavone glycosides were isolated from the MeOH extract of Melilotus neapolitana Ten. The new compound, identified as 7-O-beta-D glucopyranosyloxy-4',5-dihydroxy-3-[O-alpha-L-rhamnopyranosyl-(1-->6)-3-O-beta-D glucopyranosyloxy]flavone (1) by 1D and 2D NMR techniques and mass spectra, was isolated along with kaempferol-3-O-rutinoside (2), kaempferol-3-O-glucoside (3), rutin (4), quercetin-3-O-glucoside (5), isorhamnetin-3-O-rutinoside (6), and isorhamnetin-3-O-glucoside (7). The antioxidant and radical scavenging activities of these compounds and the whole crude methanol extract were evaluated. The organic extract can inhibit MDA marker's synthesis by 57%. All the metabolites displayed good reducing power, with the kaempferol (2,3) and isorhamnetin derivatives (6,7) being less active than the corresponding quercetin derivatives 4,5. PMID- 17846578 TI - Synthesis and biological evaluation of rigid polycyclic derivatives of the Diels Alder adduct tricyclo[6.2.1.02,7]undeca-4,9-dien-3,6-dione. AB - Part of our research program concentrates on the discovery of new bioactive compounds prepared either by total synthesis or molecular transformation of compounds with bioactivity profiles. In this work we have focused our interest on chemical transformations of the Diels-Alder adduct tricyclo[6.2.1.0(2,7)]undeca 4,9-dien-3,6-dione in order to obtain cage-like compounds and derivatives, followed by an evaluation of their biological activity. PMID- 17846579 TI - Alpine microorganisms: useful tools for low-temperature bioremediation. AB - Cold environments, including polar and alpine regions, are colonized by a wide diversity of microorganisms able to thrive at low temperatures. There is evidence of a wide range of metabolic activities in alpine cold ecosystems. Like polar microorganisms, alpine microorganisms play a key ecological role in their natural habitats for nutrient cycling, litter degradation, and many other processes. A number of studies have demonstrated the capacity of alpine microorganisms to degrade efficiently a wide range of hydrocarbons, including phenol, phenol related compounds and petroleum hydrocarbons, and the feasibility of low temperature bioremediation of European alpine soils by stimulating the degradation capacity of indigenous microorganisms has also been shown. PMID- 17846580 TI - Resistance to macrolide, lincosamide and streptogramin antibiotics in staphylococci isolated in Istanbul, Turkey. AB - The purpose of this study was to investigate the prevalence and genetic mechanisms of erythromycin resistance in staphylococci. A total of 102 erythromycin resistant non-duplicate clinical isolates of staphylococci [78 coagulase negative stapylococci (CNS), 24 Staphylococcus aureus] were collected between October 2003 and August 2004 in Istanbul Faculty of Medicine in Turkey. The majority of the isolates were from blood and urine specimens. Antimicrobial susceptibilities were determined by the agar dilution procedure and the resistance phenotypes by the double disk induction test. A multiplex PCR was performed, using primers specific for erm(A), erm(B), erm(C), and msrA genes. Among the 78 CNS isolates, 57.8% expressed the MLSB-constitutive, 20.6% the MLSB inducible, and 21.6% the MSB phenotypes. By PCR, 78.2% of these isolates harbored the erm(C) gene, 8.9% erm(A), 6.4% erm(B), and 11.5% msrA genes. In S. aureus, the constitutive MLSB (58.3%) was more common than the inducible phenotype (20.8%). erm(A) was detected in 50% and erm(C) in 62.5% of the isolates, while 37.5% contained both erm(A) and erm(C). erm(C)-associated macrolide resistance was the most prevalent in CNS, while erm(C) and erm(A, C) was the most prevalent in S. aureus. PMID- 17846581 TI - Effect of Leuconostoc spp. on the formation of Streptococcus mutans biofilm. AB - Insoluble glucans synthesized by Streptococcus mutans enhance the pathogenicity of oral biofilm by promoting the adherence and accumulation of cariogenic bacteria on the surface of the tooth. The objective of this study was to investigate the effect of Leuconostoc spp. on the in vitro formation of S. mutans biofilm. Three strains, Leuconostoc gelidum ATCC 49366, Leuconostoc mesenteroides ssp. cremoris ATCC 19254 and Leuconostoc mesenteroides ssp. mesenteroides ATCC 8293, were used in this study. They exhibited profound inhibitory effects on the formation of S. mutans biofilm and on the proliferation of S. mutans. The water soluble polymers produced from sucrose were most strongly produced by L. gelidum, followed by L. mesenteroides ssp. cremoris and L. mesenteroides ssp. mesenteroides. The mean wet weights of the artificial biofilm of S. mutans were also significantly reduced as a result of the addition of the water-soluble polymers obtained from Leuconostoc cultures. According to the results of thin layer chromatographic analysis, the hydrolysates of the water-soluble polymers produced by Leuconostoc were identical to those of dextran T-2000, forming predominately alpha-(1-6) glucose linkages. These results indicate that dextran producing Leuconostoc strains are able to inhibit the formation of S. mutans biofilm in vitro. PMID- 17846582 TI - Rapid detection of virulence factors of Aeromonas isolated from a trout farm by hexaplex-PCR. AB - The detection of virulence factors of Aeromonas is a key component in determining potential pathogenicity because these factors act multifunctionally and multifactorially. In this study water samples were collected from a trout farm on a seasonal basis, and diseased fish and Aeromonas species were isolated and identified. For rapid detection of six virulence factors of isolated Aeromonas, a hexaplex-polymerase chain reaction (hexaplex-PCR) assay was used. The detected virulence factors include aerolysin (aer), GCAT (gcat), serine protease (ser), nuclease (nuc) lipase (lip) and lateral flagella (laf). The dominant strain found in our isolates was Aeromonas sobria, and the dominant virulence factors were aer and nuc for all seasons. We confirmed that A. sobria and two of the virulence genes (aer and nuc) are related. We proposed a method by which one can identify the major strains of Aeromonas: A. hydrophila, A. sobria, A. caviae, and A. veronii, using hexaplex-PCR. PMID- 17846583 TI - Comparison of cytokine and nitric oxide induction in murine macrophages between whole cell and enzymatically digested Bifidobacterium sp. obtained from monogastric animals. AB - The principal objective of this study was to compare the effects of whole and hydrolyzed cells (bifidobacteria) treated with gastrointestinal digestive enzymes on the activation of cloned macrophages. Seven different strains of Bifidobacterium obtained from swine, chickens, and rats, were digested with pepsin followed by pancreatin and the precipitate (insoluble fraction) and supernatant (soluble fraction) obtained via centrifugation. The RAW 264.7 murine macrophages were incubated with either whole cells, the precipitate, or supernatant at various concentrations. Pronounced increases in the levels of nitric oxide (NO), interleukin (IL)-1beta, IL-6, IL-12, and tumor necrosis factor (TNF)-alpha were observed in the whole cells and precipitates, but these effects were less profound in the supernatants. The precipitates also evidenced a slight, but significant, inductive activity for NO and all tested cytokines, with the exception of TNF-alpha in the macrophage model as compared with the whole cells. By way of contrast, TNF-alpha production when cultured with whole cells (100 ng/ml) resulted in marked increases as compared with what was observed with the precipitates. The results of this study indicated, for the first time, that digested Bifidobacterium sp. can induce the production of NO and several cytokines in RAW 264.7 murine macrophage cells. In the current study, it was demonstrated that Bifidobacterium strains treated with digestive enzymes, as compared with whole cells, are capable of stimulating the induction of macrophage mediators, which reflects that they may be able to modulate the gastrointestinal immune functions of the host. PMID- 17846584 TI - Phosphate and carbon source regulation of alkaline phosphatase and phospholipase in Vibrio vulnificus. AB - In this study, the effects of phosphate concentration and carbon source on the patterns of alkaline phosphatase (APase) and phospholipase (PLase) expression in Vibrio vulnificus ATCC 29307 were assessed under various conditions. The activities of these enzymes were repressed by excess phosphate (4 mM) in the culture medium, but this repression was reversed upon the onset of phosphate starvation in low phosphate defined medium (LPDM) containing 0.2 mM of phosphate at approximately the end of the exponential growth phase. The expressions of the two enzymes were also influenced by different carbon sources, including glucose, fructose, maltose, glycerol, and sodium acetate at different levels. The APase activity was derepressed most profoundly in LPDM containing fructose as a sole carbon source. However, the repression/derepression of the enzyme by phosphate was not observed in media containing glycerol or sodium acetate. In LPDM-glycerol or sodium acetate, the growth rate was quite low. The highest levels of PLase activity were detected in LPDMsodium acetate, followed by LPDM-fructose. PLase was not fully repressed by high phosphate concentrations when sodium acetate was utilized as the sole carbon source. These results showed that multiple regulatory systems, including the phosphate regulon, may perform a function in the expression of both or either APase and PLC, in the broader context of the survival of V. vulnificus. PMID- 17846585 TI - Isoforms of glucose 6-phosphate dehydrogenase in Deinococcus radiophilus. AB - Glucose 6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49) in Deinococcus radiophilus, an extraordinarily UV-resistant bacterium, was investigated to gain insight into its resistance as it was shown to be involved in a scavenging system of superoxide (O2-1) and peroxide (O2-2) generated by UV and oxidative stresses. D. radiophilus possesses two G6PDH isoforms: G6PDH-1 and G6PDH-2, both showing dual coenzyme specificity for NAD and NADP. Both enzymes were detected throughout the growth phase; however, the substantial increase in G6PDH-1 observed at stationary phase or as the results of external oxidative stress indicates that this enzyme is inducible under stressful environmental conditions. The G6PDH-1 and G6PDH-2 were purified 122- and 44-fold (using NADP as cofactor), respectively. The purified G6PDH-1 and G6PDH-2 had the specific activity of 2,890 and 1,033 U/mg protein (using NADP as cofactor) and 3,078 and 1,076 U/mg protein (using NAD as cofactor), respectively. The isoforms also evidenced distinct structures; G6PDH-1 was a tetramer of 35 kDa subunits, whereas G6PDH-2 was a dimer of 60 kDa subunits. The pIs of G6PDH-1 and G6PDH-2 were 6.4 and 5.7, respectively. Both G6PDH-1 and G6PDH-2 were inhibited by both ATP and oleic acid, but G6PDH-1 was found to be more susceptible to oleic acid than G6PDH-2. The profound inhibition of both enzymes by beta-naphthoquinone-4-sulfonic acid suggests the involvement of lysine at their active sites. Cu2+ was a potent inhibitor to G6PDH-2, but a lesser degree to G6PDH-1. Both G6PDH-1 and G6PDH-2 showed an optimum activity at pH 8.0 and 30 degrees . PMID- 17846586 TI - The physiological role of CPR1 in Saccharomyces cerevisiae KNU5377 against menadione stress by proteomics. AB - In order to understand the functional role of CPR1 in Saccharomyces cerevisiae KNU5377 with regard to its multi-tolerance characteristics against high temperatures, inorganic acids, and oxidative stress conditions, whole cellular proteins were analyzed via liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). This procedure was followed by two-dimensional (2-D) gel electrophoresis. Under menadione stress conditions, the 23 upregulated proteins were clearly identified only in the wildtype strain of KNU5377. Among the proteins, Sod1p, Tsa1p, Ahp1, Cpr1p, Cpr3, Ssb2p, and Hsp12p were identified as components of antioxidant systems or protein-folding related systems. The CPR1 protein could not be completely detected in the cpr1Delta mutant of KNU5377 and the other upregulated proteins in the wild-type strain evidenced a clear correlation with the results of immunoblot analysis. Moreover, a reduction in growth patterns (about 50%) could be observed in the cpr1Delta mutant, as compared with that of the wild-type strain under mild MD stress conditions. These results indicate that the upregulation of CPR1 may contribute to tolerance against MD as an inducer of oxidative stress. PMID- 17846587 TI - Purification and characterization of an intracellular NADH: quinone reductase from Trametes versicolor. AB - Intracellular NADH:quinone reductase involved in degradation of aromatic compounds including lignin was purified and characterized from white rot fungus Trametes versicolor. The activity of quinone reductase was maximal after 3 days of incubation in fungal culture, and the enzyme was purified to homogeneity using ion-exchange, hydrophobic interaction, and gel filtration chromatographies. The purified enzyme has a molecular mass of 41 kDa as determined by SDS-PAGE, and exhibits a broad temperature optimum between 20-40 degrees C , with a pH optimum of 6.0. The enzyme preferred FAD as a cofactor and NADH rather than NADPH as an electron donor. Among quinone compounds tested as substrate, menadione showed the highest enzyme activity followed by 1,4-benzoquinone. The enzyme activity was inhibited by CuSO(4), HgCl(2), MgSO(4), MnSO(4), AgNO(3), dicumarol, KCN, NaN(3), and EDTA. Its Km and Vmax with NADH as an electron donor were 23 microM and 101 mM/mg per min, respectively, and showed a high substrate affinity. Purified quinone reductase could reduce 1,4-benzoquinone to hydroquinone, and induction of this enzyme was higher by 1,4-benzoquinone than those of other quinone compounds. PMID- 17846588 TI - Screening of genes related to methylglyoxal susceptibility. AB - Methylglyoxal (MG) is a reactive metabolite known to accumulate in certain physiological conditions. We attempted to isolate genes associated with this metabolite by genome-wide mutagenesis with TnphoA derivative. After screening on methylglyoxal-containing plate, we obtained insertions in three different genes, ydbD, yjjQ, and yqiI, which gave rise to reproducible MG-sensitive phenotypes in glyoxalase-deficient strain. In addition to its MG sensitivity, the insertion in yqiI exhibited an impaired motility resulting from a reduced flagellar expression. PMID- 17846589 TI - Schizosaccharomyces pombe nup97, which Genetically Interacts with mex67, is essential for growth and involved in mRNA export. AB - We have isolated previously three synthetic lethal mutants in Schizosaccharomyces pombe, which genetically interact with mex67, in order to identify the genes involved in mRNA export. A novel nup97 gene was isolated by complementation of the growth defect in one of the synthetic lethal mutants, SLMex3. The nup97 gene contains one intron and encodes an 851 amino-acid protein that is similar to nucleoporins, Npp106p in S. pombe and Nic96p in Saccharomyces cerevisiae. The nup97 gene is essential for vegetative growth, and nup97 null mutant harboring pREP41X-Nup97 showed poly(A)+ RNA export defect when expression of nup97 is repressed in the presence of thiamine. These results suggest that nup97 is involved in mRNA export from the nucleus to cytoplasm. PMID- 17846590 TI - Effect of Saliva miltiorrhiza bunge on antimicrobial activity and resistant gene regulation against methicillin-resistant Staphylococcus aureus (MRSA). AB - This study was conducted in an effort to evaluate the antimicrobial activity and antibiotic-resistant gene regulation from Saliva miltiorrhiza Bunge on methicillin-resistant Staphylococcus aureus (MRSA). A variety of solvent fractions and methanol extracts of S. miltiorrhiza Bunge were tested in order to determine its antimicrobial activities against S. aureus and MRSA. As a result, the hexane fraction of S. miltiorrhiza Bunge evidenced the highest levels of antimicrobial activity against S. aureus and MRSA. The MICs of the hexane fraction against various MRSA specimens were 64 or =2 x 10(6) CD34(+)/kg) and the median PBSC collection per procedure was 2.18 x 10(6)/kg (range 0.1-14.5). Only more lines of prior chemotherapy predicted failure to harvest in multivariate analysis (P=0.003). The PB CD34(+) cell count correlated significantly with harvest yield (r=0.8448, P<0.0001). A PB CD34(+) count > or =10/microl predicted a collection of > or =2 x 10(6)/kg (positive predictive value of 61%, negative-predictive-value 100%). Patients first attending day 9 required significantly fewer visits to achieve a successful harvest than those first attending days 6-8 without increasing the risk of failure. No significant difference in failure rates, number of days attending and total harvest yield was found between days 9 and 10 attendees. Collection from day 9 may however enable higher target yields to be achieved. PB CD34(+) count monitoring should commence and harvesting booked from day 9 to optimize both the harvest and the efficiency of the PBSC harvesting service. PMID- 17846600 TI - The influence of palifermin (Kepivance) on oral mucositis and acute graft versus host disease in patients with hematological diseases undergoing hematopoietic stem cell transplant. AB - In this multicenter study, we assessed the use of palifermin (recombinant human keratinocyte growth factor 1) in the prevention of oral mucositis (OM) and acute GvHD (aGvHD) induced by a hematopoietic stem cell transplant (HSCT). Fifty-three patients with hematological diseases received three doses of palifermin (60 mug/kg once daily i.v.) pre- and post-conditioning regimens (total six doses). A retrospective control group of 53 transplant patients received no palifermin. There was a significant reduction in the incidence of OM of WHO (World Health Organization) grades 1-4 (58 vs 94%, P<0.001), 3-4 (13 vs 43%, P<0.001) and the median duration of OM (4 vs 9 days, P<0.001) in the palifermin group compared to the control group. The incidence of analgesics (32 vs 75.5%, P<0.001), opioid analgesics (24 vs 64%, P<0.001) and total parenteral nutrition (11 vs 45%, P<0.001) was also significantly reduced. The analysis of distribution of affected organs revealed that aGvHD was less prevalent in the palifermin group (P=0.036). There was no significant difference in the onset of any OM after HSCT, time to engraftment and length of hospitalization between groups. The drug was generally well tolerated and safe. Our results suggest that the use of palifermin reduces OM and probably aGvHD after HSCT, but a randomized trial is needed. PMID- 17846601 TI - Granulocyte and erythropoietic stimulating proteins after high-dose chemotherapy for myeloma. AB - High-dose chemotherapy is an established treatment for patients with myeloma. In randomized trials it has been shown to prolong disease-free survival by around 1 year compared to patients receiving chemotherapy alone. Physically and psychologically high-dose therapy takes its toll on the patient who may be in hospital for around 3 weeks and take some weeks or months to convalesce after discharge. Granulocyte colony stimulating factors and erythropoietic stimulating agents will speed neutrophil and red cell recovery, respectively, when used at an appropriate time after the high-dose chemotherapy. The clinical value of these laboratory findings is uncertain and the role of these agents after high-dose chemotherapy remains a subject for debate. PMID- 17846602 TI - Multicenter study of intravenous busulfan, cyclophosphamide, and etoposide (i.v. Bu/Cy/E) as conditioning regimen for autologous stem cell transplantation in patients with non-Hodgkin's lymphoma. AB - The current study aimed to evaluate the efficacy and toxicity of a combination of intravenous busulfan, cyclophosphamide and etoposide (i.v. Bu/Cy/E) as a conditioning regimen prior to autologous hematopoietic stem cell transplantation in patients with non-Hodgkin's lymphoma (NHL). Sixty-four patients with relapsed/refractory (n=36) or high-risk (n=28) lymphoma were enrolled. The high dose chemotherapy consisted of i.v. Bu (0.8 mg kg(-1) i.v. q 6 h from day -7 to day -5), Cy (50 mg kg(-1) i.v. on day -3 and day -2) and E (400 mg m(-2) i.v. on day -5 and day -4). The median age was 43 (range 18-65) years, and 39 patients were male. Diffuse large B-cell lymphoma (40.6%) was the most common histological subtype. All evaluable patients achieved an engraftment of neutrophils (median, day 12) and platelets (median, day 13). Hepatic veno-occlusive disease was observed in four patients (three mild, one moderate grade), and two patients (3.1%) died from treatment-related complications. At a median follow-up of 16.4 months, 15 patients (23.4%) exhibited a relapse or progression, while 13 patients (20.3%) had died of disease. The estimated 3-year overall and progression-free survival for all patients was 72.1 and 70.1%, respectively. In conclusion, the conditioning regimen of i.v. Bu/Cy/E was well tolerated and seemed to be effective in patients with aggressive NHL. PMID- 17846603 TI - Results of donor lymphocyte infusions for relapsed myelodysplastic syndrome after hematopoietic cell transplantation. AB - Allogeneic hematopoietic cell transplantation (HCT) represents a potentially curative approach for patients with myelodysplastic syndromes (MDSs). While a large proportion of HCT recipients become long-term disease-free survivors, recurrence of MDS remains the leading cause of mortality after HCT. The role of donor lymphocyte infusion (DLI) in patients with relapsed MDS after HCT is unclear. We report results among 16 patients treated with DLI for relapsed MDS after HCT at a single institution between March 1993 and February 2004. The cohort contained 10 men and 6 women with a median age of 49 (range, 22-67) years. CR with resolution of cytopenias and prior disease markers occurred in 3 of 14 patients who could be evaluated. Two patients survived without MDS for 68 and 65 months after DLI, respectively, but died with pneumonia. Grades II-IV acute GVHD and chronic GVHD occurred after DLI in 6 (43%) and 5 (36%) patients, respectively. All three responders developed grades III-IV acute GVHD and extensive chronic GVHD after DLI. Our results confirm prior reports that DLI can result in CR in some patients with recurrent MDS after transplant, but long-term survival is infrequent. PMID- 17846604 TI - Allogeneic stem cell transplantation from matched related and unrelated donors in thalassemia major patients using a reduced toxicity fludarabine-based regimen. AB - The only radical cure for thalassemia major patients today is the replacement of the defective hematopoietic system by allogeneic stem cell transplantation (allo SCT). The major obstacles for the application of allo-SCT even from matched family members have been the transplant-related morbidity and mortality and graft failure that is usually associated with the recurrence of the thalassemia hematopoiesis. The outcome of allo-SCT from HLA-identical family donors is largely dependent on the age of the recipient as well as on pretransplant parameters reflecting the degree of organ damage from iron overload. In this study we report our experience of allo-SCT from matched related and unrelated donors, using a reduced toxicity conditioning consisting of fludarabine, busulfan or more recently busulfex and antithymocyte globulin, in a cohort of 20 patients with thalassemia major. The regimen-related toxicity was minimal, while the incidence of acute grade II-IV and chronic GVHD was 25 and 25%, respectively. With a median follow-up period of 39 months (range: 5-112 months) the overall survival was 100%, while thalassemia-free survival was 80%. Although the results of our study look promising, larger cohorts of patients and prospective clinical trials are required to confirm the benefits of our approach as a possible better alternative to the existing protocols. PMID- 17846605 TI - Six cases of permanent alopecia after various conditioning regimens commonly used in hematopoietic stem cell transplantation. AB - Alopecia, a side effect of chemotherapy, is usually temporary and reversible. Irreversible alopecia has been reported after high-dose chemotherapy (HDC) and hematopoietic stem cell transplantation (HSCT) especially related to BuCy containing conditioning regimens; however, the overall incidence is not known. We conducted a retrospective study to identify patients with chemotherapy-induced permanent alopecia after HSCT. We describe six such patients, two males and four females, among 760 patients transplanted between 1997 and 2004. Median age was 45 years (range, 37-65). There were three Caucasians and three African-Americans. Median follow-up was 30 months. Conditioning regimens included BuCy, Bu/Cy and etoposide (VP16) (one of these patients received second autograft after Cy and TBI) and CyVP16 and TBI. Our data show that permanent alopecia is a significant long-term side effect of HSCT and can be seen across the spectrum of diseases and transplant types and with non-busulfan containing regimens. We have observed that patients usually accept permanent alopecia as the price for the cure and therefore true incidence of permanent alopecia may be underestimated. Our findings may also have medico legal and psychosocial implications that need to be taken into consideration when consenting patients for HSCT. PMID- 17846606 TI - Retracing events. PMID- 17846607 TI - Access all areas. PMID- 17846608 TI - A tragic GM "outing". PMID- 17846609 TI - Funding crunch forces stem cell company to abandon therapies. PMID- 17846610 TI - Glycerin bioprocessing goes green. PMID- 17846611 TI - ZymoGenetics' moves recall young Genentech. PMID- 17846612 TI - BioPolis report paints fractured picture of EU biotech. PMID- 17846614 TI - Trends in biotech literature 2006. PMID- 17846615 TI - Blooming biotech. PMID- 17846616 TI - The other side of staying out of a BIND. PMID- 17846617 TI - The other side of staying out of a BIND. PMID- 17846618 TI - The Genasense 'learning curve'. PMID- 17846619 TI - Ethical framework for previously collected biobank samples. PMID- 17846621 TI - NIH forges R&D partnerships in developing countries. PMID- 17846622 TI - North-South partnerships--a study of Canadian firms. PMID- 17846625 TI - Gene patents and genetic testing in the United States. PMID- 17846624 TI - GM soybeans and health safety--a controversy reexamined. PMID- 17846626 TI - Recent patent applications in stem cell culture. PMID- 17846627 TI - ES cells for troubled hearts. PMID- 17846628 TI - On the iTRAQ of kinase inhibitors. PMID- 17846629 TI - Mustering the micromanagers. PMID- 17846631 TI - Ensemble modeling for analysis of cell signaling dynamics. AB - Systems biology iteratively combines experimentation with mathematical modeling. However, limited mechanistic knowledge, conflicting hypotheses and scarce experimental data severely hamper the development of predictive mechanistic models in many areas of biology. Even under such high uncertainty, we show here that ensemble modeling, when combined with targeted experimental analysis, can unravel key operating principles in complex cellular pathways. For proof of concept, we develop a library of mechanistically alternative dynamic models for the highly conserved target-of-rapamycin (TOR) pathway of Saccharomyces cerevisiae. In contrast to the prevailing view of a de novo assembly of type 2A phosphatases (PP2As), our integrated computational and experimental analysis proposes a specificity factor, based on Tap42p-Tip41p, for PP2As as the key signaling mechanism that is quantitatively consistent with all available experimental data. Beyond revising our picture of TOR signaling, we expect ensemble modeling to help elucidate other insufficiently characterized cellular circuits. PMID- 17846634 TI - Managing change in biotech: setbacks and failures. PMID- 17846636 TI - Gene conversion: mechanisms, evolution and human disease. AB - Gene conversion, one of the two mechanisms of homologous recombination, involves the unidirectional transfer of genetic material from a 'donor' sequence to a highly homologous 'acceptor'. Considerable progress has been made in understanding the molecular mechanisms that underlie gene conversion, its formative role in human genome evolution and its implications for human inherited disease. Here we assess current thinking about how gene conversion occurs, explore the key part it has played in fashioning extant human genes, and carry out a meta-analysis of gene-conversion events that are known to have caused human genetic disease. PMID- 17846638 TI - Acute flaccid paraplegia: a rare complication of meningococcal meningitis. AB - STUDY DESIGN: A case report of spinal cord dysfunction following meningococcal meningitis. OBJECTIVES: To describe a rare complication of meningococcal meningitis. SETTING: Spinal Unit, Armed Forces Institute of Rehabilitation Medicine, Rawalpindi, Pakistan. METHODS: A young healthy male developed meningococcal meningitis followed by acute onset low thoracic flaccid paraplegia with complete motor and sensory loss and sphincter disturbance. He responded well to antibiotics but was not investigated for causes of paraplegia. While at home in a rural area, he developed pressure ulcers, anemia and depression. Magnetic resonance imaging of the whole spine and computed tomography scan of the brain performed after 4 and 10 weeks were normal. RESULTS: The patient had a comprehensive rehabilitation at our institute. Recovery was complicated by ossification in the right thigh, which responded well to radiotherapy. At 1-year follow-up, the motor deficit and neurogenic bladder and bowel persisted and the patient remained wheelchair dependent for mobility. CONCLUSION: Several mechanisms have been proposed to explain spinal cord damage after meningitis. These include spinal cord infarction; autoimmune-mediated inflammatory myelopathy and direct infection of the cord. Most probable cause of spinal cord dysfunction in this case was thoracic myelopathy. PMID- 17846639 TI - Functional electrical stimulation after spinal cord injury: current use, therapeutic effects and future directions. AB - Repair of the injured spinal cord by regeneration therapy remains an elusive goal. In contrast, progress in medical care and rehabilitation has resulted in improved health and function of persons with spinal cord injury (SCI). In the absence of a cure, raising the level of achievable function in mobility and self care will first and foremost depend on creative use of the rapidly advancing technology that has been so widely applied in our society. Building on achievements in microelectronics, microprocessing and neuroscience, rehabilitation medicine scientists have succeeded in developing functional electrical stimulation (FES) systems that enable certain individuals with SCI to use their paralyzed hands, arms, trunk, legs and diaphragm for functional purposes and gain a degree of control over bladder and bowel evacuation. This review presents an overview of the progress made, describes the current challenges and suggests ways to improve further FES systems and make these more widely available. PMID- 17846640 TI - Quantitative and qualitative in vitro analysis of the stem cell potential of hematopoietic cells purified from murine skeletal muscle. AB - The murine skeletal muscle contains hematopoietic stem cells, but this potential has so far not been studied quantitatively or qualitatively in vitro. To quantify the hematopoietic stem cell potential, we have used highly purified SP/CD45(+) cells in long-term culture initiating cell (LTC-IC) assays. The SP/CD45(+) cell population purified from murine muscle was found to have significant stem cell activity with an LTC-IC frequency of 1/640. Single-cell-sorted SP/CD45(+) cells from muscle exhibited robust proliferative activity in vitro at day 16 (380-fold amplification), especially after culture with OP-9 layers that also support embryonic stem cells. Amplified cell populations originating from single cells exhibited multilineage differentiation ability with evidence of myeloid, lymphoid and NK cell markers. Thus, our results demonstrate that hematopoietic stem cells that can be quantified by LTC-IC assays exist in the murine skeletal muscle and show also for the first time, at the single-cell level, that these cells exhibit multilineage differentiation ability and major proliferative potential. PMID- 17846637 TI - Ribozymes, riboswitches and beyond: regulation of gene expression without proteins. AB - Although various functions of RNA are carried out in conjunction with proteins, some catalytic RNAs, or ribozymes, which contribute to a range of cellular processes, require little or no assistance from proteins. Furthermore, the discovery of metabolite-sensing riboswitches and other types of RNA sensors has revealed RNA-based mechanisms that cells use to regulate gene expression in response to internal and external changes. Structural studies have shown how these RNAs can carry out a range of functions. In addition, the contribution of ribozymes and riboswitches to gene expression is being revealed as far more widespread than was previously appreciated. These findings have implications for understanding how cellular functions might have evolved from RNA-based origins. PMID- 17846642 TI - A heuristic technique for CTIS image reconstruction. AB - An iterative method is presented for computed tomography imaging spectrometer (CTIS) image reconstruction in the presence of both photon noise in the image and postdetection Gaussian system noise. The new algorithm, which assumes the transfer matrix of the system has a particular structure, is evaluated experimentally with the result that it is significantly better, for larger problems, than both the multiplicative algebraic reconstruction technique (MART) and the mixed-expectation image-reconstruction technique (MERT) with respect to accuracy and computation time. PMID- 17846641 TI - Glut-4 is translocated to both caveolae and non-caveolar lipid rafts, but is partially internalized through caveolae in insulin-stimulated adipocytes. AB - Caveolae and non-caveolar lipid rafts are two types of membrane lipid microdomains that play important roles in insulin-stimulated glucose uptake in adipocytes. In order to ascertain their specific functions in this process, caveolae were ablated by caveolin-1 RNA interference. In Cav-1 RNAi adipocytes, neither insulin-stimulated glucose uptake nor Glut-4 (glucose transporter 4) translocation to membrane lipid microdomains was affected by the ablation of caveolae. With a modified sucrose density gradient, caveolae and non-caveolar lipid rafts could be separated. In the wild-type 3T3-L1 adipocytes, Glut-4 was found to be translocated into both caveolae and non-caveolar lipid rafts. However, in Cav-1 RNAi adipocytes, Glut-4 was localized predominantly in non caveolar lipid rafts. After the removal of insulin, caveolae-localized Glut-4 was internalized faster than non-caveolar lipid raft-associated Glut-4. The internalization of Glut-4 from plasma membrane was significantly decreased in Cav 1 RNAi adipocytes. These results suggest that insulin-stimulated Glut-4 translocation and glucose uptake are caveolae-independent events. Caveolae play a role in the internalization of Glut-4 from plasma membrane after the removal of insulin. PMID- 17846643 TI - Atmospheric correction for NO2 absorption in retrieving water-leaving reflectances from the SeaWiFS and MODIS measurements. AB - The absorption by atmospheric nitrogen dioxide (NO2) gas in the visible has been traditionally neglected in the retrieval of oceanic parameters from satellite measurements. Recent measurements of NO2 from spaceborne sensors show that over the Eastern United States the NO2 column amount often exceeds 1 Dobson Unit (approximately 2.69x10(16) molecules/cm2). Our radiative transfer sensitivity calculations show that under high NO2 conditions (approximately 1x10(16) molecules/cm2) the error in top-of-atmosphere (TOA) reflectance in the blue channels of the sea-viewing wide field-of-view sensor (SeaWiFS) and moderate resolution imaging spectroradiometer (MODIS) sensors is approximately 1%. This translates into approximately 10% error in water-leaving radiance for clear waters and to higher values (>20%) in the coastal areas. We have developed an atmospheric-correction algorithm that allows an accurate retrieval of normalized water-leaving radiances (nLws) in the presence of NO2 in the atmosphere. The application of the algorithm to 52 MODIS scenes over the Chesapeake Bay area show a decrease in the frequency of negative nLw estimates in the 412 nm band and an increase in the value of nLws in the same band. For the particular scene reported in this paper, the mean value of nLws in the 412 nm band increased by 17%, which is significant, because for the MODIS sensor the error in nLws attributable to the digitization error in the observed TOA reflectance over case 2 waters is approximately 2.5%. PMID- 17846644 TI - Maximizing the opening of eye diagrams for slow-light systems. AB - We present a data-fidelity metric for quantifying distortion in slow-light optical pulse delay devices. We demonstrate the utility of this metric by applying it to the performance optimization of gain-based slow-light delay systems for Gaussian and super-Gaussian pulses. Symmetric Lorentzian double-line and triple-line gain systems are optimized and achieve maximum delay of 1.5 and 1.7 times the single-line gain system delay, respectively. The resulting double line gain system design is qualitatively similar to the double-line gain system designed with a previous metric, but is tuned specifically to constrain data fidelity. PMID- 17846645 TI - Simple technique for the fabrication of a penta prism with high accuracy right angle deviation. AB - What we believe to be a new technique for the fabrication of a penta prism (PP) with high accuracy right angle deviation of the incident beam is presented. We derive simple formulas relating to the error in right angle deviation with the errors in 45 degrees (beta) and 90 degrees (delta) angles of a PP, and we determine error in right angle deviation from the angle ((error in right angle deviation)r) between the plane wavefronts reflected from the right angled surfaces (external Fresnel reflection on the entrance surface and internal Fresnel reflection on the exit surface) of a PP and the angular error (delta) between the same surfaces. The error in right angle deviation is determined from the measurement of (error in right angle deviation)r using an autocollimator and a Fizeau interferometer, and error in right angle deviation is corrected to a high order of accuracy during the final stage of polishing one of the slanted surfaces of the PP. A new technique to determine the magnitude and direction of the small values of (error in right angle deviation)r is proposed and verified. The result for a PP is presented. PMID- 17846646 TI - Effect of photochemistry on molecular detection by cavity ringdown spectroscopy: case study of an explosive-related compound. AB - Explosives and explosive-related compounds usually have dissociative excited electronic states. We consider the effect of excited-state dissociation upon an absorption event on the UV cavity ringdown spectroscopy (CRDS) detection of these molecules. A change in the photon decay lifetime with increasing laser energy is demonstrated with vapors of 2,6-dinitrotoluene in the open atmosphere. The magnitude of the effect is modeled with coupled equations describing the time dependent light intensity and molecular concentration within the cavity. The light intensities required within this model to explain the observed changes in the photon decay lifetimes are consistent with the light intensities expected within the cavity under our experimental conditions. It was also found that the slow diffusion of the molecules in static air can magnify the effect of photochemistry on UV CRDS trace detection of molecules with dissociative excited states. PMID- 17846647 TI - Design of optical path for wide-angle gradient-index antireflection coatings. AB - What we believe to be a new principle is introduced for the design and selection of gradient-index antireflection profiles that are effective over a wide range of incident angles as well as wavelengths at a given physical film thickness. It is shown that at oblique incidence the smoothness of the optical path of incident light inside a gradient-index film has a crucial effect on the overall reflection. Thus the smoothness of variations in refractive angle (rather than that of the index profile itself) needs to be maximized for wide-angle operation. As an example, the performance of Gaussian and Quintic profiles at large incident angles are considered in light of this point of view. PMID- 17846648 TI - Near-diffraction-limited green source by frequency doubling of a diode-stack pumped Q-switched Nd:YAG slab oscillator-amplifier system. AB - A near-diffraction-limited, stable, 18 mJ green source with a pulse width of 16.7 ns was generated at a 1 kHz repetition rate by frequency doubling of diode stacks end-pumped electro-optically Q-switched slab Nd:YAG oscillator-amplifier system. The pump to green optical conversion efficiency was 10.7%. At the output energy of 15 mJ at 532 nm, the M2 factors were 1.3 and 1.7 in the unstable and stable directions, respectively. The energy pulse stability was approximately 0.8%. PMID- 17846649 TI - Adaptive phase-input joint transform correlator. AB - An adaptive phase-input joint transform correlator for pattern recognition is presented. The input of the system is two phase-only images: input scene and reference. The reference image is generated with a new iterative algorithm using phase-only synthetic discriminant functions. The algorithm takes into account calibration lookup tables of all optoelectronics elements used in optodigital experiments. The designed adaptive phase-input joint transform correlator is able to reliably detect a target and its distorted versions embedded into a cluttered background. Computer simulations are provided and compared with those of various existing joint transform correlators in terms of discrimination capability, tolerance to input additive noise, and to small geometric image distortions. Experimental optodigital results are also provided and discussed. PMID- 17846650 TI - Angular distribution of diffuse reflectance in biological tissue. AB - We measured angular-resolved diffuse reflectance in tissue samples of different anisotropic characteristics. Experimental measurements were compared with theoretical results based on the diffusion approximation. The results indicated that the angular distribution in isotropic tissue was the same as in isotropic phantoms. Under normal incidence, the measured angular profiles of diffuse reflectance approached the Lambertian distribution when the evaluation location was far away from the incident point. The skewed angular profiles observed under oblique incidence could be explained using the diffuse model. The anisotropic tissue structures in muscle showed clear effects on the measurements especially at locations close to the light incidence. However, when measuring across the muscle fiber orientations, the results were in good agreement with those obtained in isotropic samples. PMID- 17846651 TI - Spatial correlation and irradiance statistics in a multiple-beam terrestrial free space optical communication link. AB - By means of numerical simulations we analyze the statistical properties of the power fluctuations induced by the incoherent superposition of multiple transmitted laser beams in a terrestrial free-space optical communication link. The measured signals arising from different transmitted optical beams are found to be statistically correlated. This channel correlation increases with receiver aperture and propagation distance. We find a simple scaling rule for the spatial correlation coefficient in terms of the propagation distance and we are able to predict the scintillation reduction in previously reported experiments with good accuracy. We propose an approximation to the probability density function of the received power of a spatially correlated multiple-beam system in terms of the parameters of the single-channel gamma-gamma function. A bit-error-rate evaluation is also presented to demonstrate the improvement of a multibeam system over its single-beam counterpart. PMID- 17846652 TI - Coupling of surface roughness to the performance of computer-generated holograms. AB - Computer-generated holograms (CGHs), such as those used in optical testing, are created by etching patterns into an optical substrate. Imperfections in the etching can cause small scale surface roughness that varies across the pattern. The variation in this roughness affects the phase and amplitude of the wavefronts in the various diffraction orders. A simplified model is developed and validated that treats the scattering loss from the roughness as an amplitude effect. We demonstrate the use of this model for engineering analysis and provide a graphical method for understanding the application. Furthermore, we investigate the magnitude of this effect for the application of optical testing and show that the effect on measurement accuracy is limited to 1 nm for typical CGHs. PMID- 17846653 TI - Role of minerogenic particles in light scattering in lakes and a river in central New York. AB - The role of minerogenic particles in light scattering in several lakes and a river (total of ten sites) in central New York, which represent a robust range of scattering conditions, was evaluated based on an individual particle analysis technique of scanning electron microscopy interfaced with automated x-ray microanalysis and image analysis (SAX), in situ bulk measurements of particle scattering and backscattering coefficients (bp and bbp), and laboratory analyses of common indicators of scattering. SAX provided characterizations of the elemental x-ray composition, number concentration, particle size distribution (PSD), shape, and projected area concentration of minerogenic particles (PAVm) of sizes>0.4 microm. Mie theory was applied to calculate the minerogenic components of bp (bm) and bbp (bb,m) with SAX data. Differences in PAVm, associated primarily with clay minerals and CaCO3, were responsible for most of the measured differences in both bp and bbp across the study sites. Contributions of the specified minerogenic particle classes to bm were found to correspond approximately to their contributions to PAVm. The estimates of bm represented substantial fractions of bp, whereas those of bb,m were the dominant component of bbp. The representativeness of the estimates of bm and bb,m was supported by their consistency with the bulk measurements. Greater uncertainty prevails for the bb,m estimates than those for bm, associated primarily with reported deviations in particle shapes from sphericity. The PSDs were well represented by the "B" component of the two-component model or a three parameter generalized gamma distribution [Deep-Sea Res. Part I 40, 1459 (1993)]. The widely applied Junge (hyperbolic) function performed poorly in representing the PSDs and the size dependency of light scattering in these systems, by overrepresenting the concentrations of submicrometer particles especially. Submicrometer particles were not important contributors to bm or bb,m. PMID- 17846654 TI - Model eyes for evaluation of intraocular lenses. AB - In accordance with the present international standard for intraocular lenses (IOLs), their imaging performance should be measured in a model eye having an aberration-free cornea. This was an acceptable setup when IOLs had all surfaces spherical and hence the measured result reflected the spherical aberration of the IOL. With newer IOLs designed to compensate for the spherical aberration of the cornea there is a need for a model eye with a physiological level of spherical aberration in the cornea. A literature review of recent studies indicated a fairly high amount of spherical aberration in human corneas. Two model eyes are proposed. One is a modification of the present ISO standard, replacing the current achromat doublet with an aspheric singlet cut in poly(methyl methacrylate) (PMMA). The other also has an aspheric singlet cut in PMMA, but the dimensions of it and the entire model eye are close to the physiological dimensions of the eye. They give equivalent results when the object is at infinity, but for finite object distances only the latter is correct. The two models are analyzed by calculation assuming IOLs with different degrees of asphericity to elucidate their sensitivity to variation and propose tolerances. Measured results in a variant of the modified ISO model eye are presented. PMID- 17846655 TI - Particle backscatter and extinction profiling with the spaceborne high-spectral resolution Doppler lidar ALADIN: methodology and simulations. AB - The European Space Agency will launch the Atmospheric Laser Doppler Instrument (ALADIN) for global wind profile observations in the near future. The potential of ALADIN to measure the optical properties of aerosol and cirrus, as well, is investigated based on simulations. A comprehensive data analysis scheme is developed that includes (a) the correction of Doppler-shifted particle backscatter interference in the molecular backscatter channels (cross-talk effect), (b) a procedure that allows us to check the quality of the cross-talk correction, and (c) the procedures for the independent retrieval of profiles of the volume extinction and backscatter coefficients of particles considering the height-dependent ALADIN signal resolution. The error analysis shows that the particle backscatter and extinction coefficients, and the corresponding extinction-to-backscatter ratio (lidar ratio), can be obtained with an overall (systematic+statistical) error of 10%-15%, 15%-30%, and 20%-35%, respectively, in tropospheric aerosol and dust layers with extinction values from 50 to 200 Mm( 1); 700-shot averaging (50 km horizontal resolution) is required. Vertical signal resolution is 500 m in the lower troposphere and 1000 m in the free troposphere. In cirrus characterized by extinction coefficients of 200 Mm(-1) and an optical depth of >0.2, backscatter coefficients, optical depth, and column lidar ratios can be obtained with 25%-35% relative uncertainty and a horizontal resolution of 10 km (140 shots). In the stratosphere, only the backscatter coefficient of aerosol layers and polar stratospheric clouds can be retrieved with an acceptable uncertainty of 15%-30%. Vertical resolution is 2000 m. PMID- 17846656 TI - Fast and robust three-dimensional best path phase unwrapping algorithm. AB - What we believe to be a novel three-dimensional (3D) phase unwrapping algorithm is proposed to unwrap 3D wrapped-phase volumes. It depends on a quality map to unwrap the most reliable voxels first and the least reliable voxels last. The technique follows a discrete unwrapping path to perform the unwrapping process. The performance of this technique was tested on both simulated and real wrapped phase maps. And it is found to be robust and fast compared with other 3D phase unwrapping algorithms. PMID- 17846657 TI - Responsivity optimization and stabilization in electro-optic field sensors. AB - Electro-optic (EO) modulation devices, which utilize an external electric field to modulate a beam of optical radiation, are strongly affected by parasitic effects, which change the polarization state of the optical beam. As a result, very small changes in the birefringence or optical path length within the EO material can result in very large fluctuations of the amplitude and phase of the optical modulation signal. A method of actively analyzing the modulated beam is described and demonstrated, which eliminates these fluctuations and keeps the modulation device stably operating at its peak responsivity. Applications to electric field detection and measurements are discussed. PMID- 17846658 TI - Key-space analysis of double random phase encryption technique. AB - We perform a numerical analysis on the double random phase encryption/decryption technique. The key-space of an encryption technique is the set of possible keys that can be used to encode data using that technique. In the case of a strong encryption scheme, many keys must be tried in any brute-force attack on that technique. Traditionally, designers of optical image encryption systems demonstrate only how a small number of arbitrary keys cannot decrypt a chosen encrypted image in their system. However, this type of demonstration does not discuss the properties of the key-space nor refute the feasibility of an efficient brute-force attack. To clarify these issues we present a key-space analysis of the technique. For a range of problem instances we plot the distribution of decryption errors in the key-space indicating the lack of feasibility of a simple brute-force attack. PMID- 17846659 TI - Generation of a flat-top laser beam for gravitational wave detectors by means of a nonspherical Fabry-Perot resonator. AB - We have tested a new kind of Fabry-Perot long-baseline optical resonator proposed to reduce the thermal noise sensitivity of gravitational wave interferometric detectors--the "mesa beam" cavity--whose flat top beam shape is achieved by means of an aspherical end mirror. We present the fundamental mode intensity pattern for this cavity and its distortion due to surface imperfections and tilt misalignments, and contrast the higher order mode patterns to the Gauss-Laguerre modes of a spherical mirror cavity. We discuss the effects of mirror tilts on cavity alignment and locking and present measurements of the mesa beam tilt sensitivity. PMID- 17846660 TI - Semianalytical thermal analysis of thermal focal length on Nd:YAG rods. AB - Based on the theory of semianalytical thermal analysis, the temperature field and thermal lens effects within a diode-end-pumped Nd:YAG rods were investigated. A general expression of the temperature field within Nd:YAG rods was obtained through the analysis of a diode-end-pumped Nd:YAG rod, using what we believe to be a new method to solve a heat conduction equation of isotropic material. Calculating the thermal focal length within the diode-end-pumped Nd:YAG rods was done by an analysis of the additional optical path differences caused by heat, which was in good agreement with experimental results. These results show that the maximum temperature on the pump face of Nd:YAG rods is 51.9 degrees C and the thermal focal length is 22.4 cm when the output power of the diode laser is 10 W. Under the same conditions, the experimental value of the thermal focal length is 21.0 cm. The difference between the theoretical analysis and the experimental result is only 6.7%. Results from this work can provide the theoretical basis for the optimized design of diode-end-pumped all-solid-state lasers. PMID- 17846661 TI - Protective effects of recombinant kunitz-domain 1 of human tissue factor pathway inhibitor-2 against 2-chloroethyl ethyl sulfide toxicity in vitro. AB - OBJECTIVE: Sulfur mustard is a well-known blistering chemical warfare agent that has been investigated for its toxicological mechanisms and an efficacious antidote. Since sulfur mustard injury involves dermal:epidermal separation, proteolytic enzymes were suspected to be involved for this separation and eventual blister development. Therefore, protease inhibitors could be of therapeutic utility against sulfur mustard injury. In this study, the effects of Kunitz-domain 1 of human tissue factor pathway inhibitor-2 were evaluated against the toxic effects of 2-chloroethyl ethyl sulfide, a surrogate agent of sulfur mustard. Tissue factor pathway inhibitor-2 is a 32-kDa serine protease inhibitor produced by a variety of cell types including human epidermal keratinocytes, fibroblasts, and endothelial cells. It consists of 3 Kunitz-domains and the first Kunitz-domain contains the putative P(1) residue (arginine at position 24) responsible for protease inhibitory activity. METHODS: Recombinant wild-type and R24Q mutant Kunitz-domain 1s were expressed in Escherichia coli and purified. The purified proteins were refolded, and their effects were tested in an in vitro human epidermal keratinocyte cell wounding assay. RESULTS: Wild-type but not R24Q Kunitz-domain 1 inhibited the amidolytic activity of trypsin and plasmin. Wild type Kunitz-domain1 was stable for 4 weeks at 42 degrees C and for more than 8 weeks at room temperature. Wild-type Kunitz-domain 1 significantly improved wound healing of unexposed and 2-chloroethyl ethyl sulfide-exposed cells without influencing cell proliferation. Although R24Q Kunitz-domain 1 lacked trypsin and plasmin inhibitory activity, it promoted wound closure of untreated and 2 chloroethyl ethyl sulfide-treated cells but to a much lesser degree. CONCLUSION: These data suggest that wild-type Kunitz-domain 1 of human tissue factor pathway inhibitor-2 can be developed as a medical countermeasure against sulfur mustard cutaneous injury. PMID- 17846662 TI - Analysis of gene coexpression by B-spline based CoD estimation. AB - The gene coexpression study has emerged as a novel holistic approach for microarray data analysis. Different indices have been used in exploring coexpression relationship, but each is associated with certain pitfalls. The Pearson's correlation coefficient, for example, is not capable of uncovering nonlinear pattern and directionality of coexpression. Mutual information can detect nonlinearity but fails to show directionality. The coefficient of determination (CoD) is unique in exploring different patterns of gene coexpression, but so far only applied to discrete data and the conversion of continuous microarray data to the discrete format could lead to information loss. Here, we proposed an effective algorithm, CoexPro, for gene coexpression analysis. The new algorithm is based on B-spline approximation of coexpression between a pair of genes, followed by CoD estimation. The algorithm was justified by simulation studies and by functional semantic similarity analysis. The proposed algorithm is capable of uncovering both linear and a specific class of nonlinear relationships from continuous microarray data. It can also provide suggestions for possible directionality of coexpression to the researchers. The new algorithm presents a novel model for gene coexpression and will be a valuable tool for a variety of gene expression and network studies. The application of the algorithm was demonstrated by an analysis on ligand-receptor coexpression in cancerous and noncancerous cells. The software implementing the algorithm is available upon request to the authors. PMID- 17846663 TI - Roles of retinoids and retinoic Acid receptors in the regulation of hematopoietic stem cell self-renewal and differentiation. AB - Multipotent hematopoietic stem cells (HSCs) sustain blood cell production throughout an individual's lifespan through complex processes ultimately leading to fates of self-renewal, differentiation or cell death decisions. A fine balance between these decisions in vivo allows for the size of the HSC pool to be maintained. While many key factors involved in regulating HSC/progenitor cell differentiation and cell death are known, the critical regulators of HSC self renewal are largely unknown. In recent years, however, a number of studies describing methods of increasing or decreasing the numbers of HSCs in a given population have emerged. Of major interest here are the emerging roles of retinoids in the regulation of HSCs. PMID- 17846665 TI - Effect of light curing modes and light curing time on the microhardness of a hybrid composite resin. AB - AIMS: The aim of this in vitro study was to evaluate the influence of light curing modes and curing time on the microhardness of a hybrid composite resin. METHODS AND MATERIALS: Forty-five Z250 composite resin specimens (3M-ESPE Dental Products, St. Paul, MN, USA) were randomly divided into nine groups (n=5): three polymerization modes (conventional-550 mW/cm2; light-emitting diodes (LED)-360 mW/cm2, and high intensity-1160 mW/cm2) and three light curing times (once, twice, and three times the manufacturer's recommendations). All samples were polymerized with the light tip 8 mm from the specimen. Knoop microhardness measurements were obtained on the top and bottom surfaces of the sample. RESULTS: Conventional and LED polymerization modes resulted in higher hardness means and were statistically different from the high intensity mode in almost all experimental conditions. Tripling manufacturers' recommended light curing times resulted in higher hardness means; this was statistically different from the other times for all polymerization modes in the bottom surface of specimens. This was also true of the top surface of specimens cured using the high intensity mode but not of conventional and LED modes using any of the chosen curing times. Top surfaces showed higher hardness than bottom surfaces. CONCLUSIONS: It is important to increase the light curing time and use appropriate light curing devices to polymerize resin composite in deep cavities to maximize the hardness of hybrid composite resins. PMID- 17846664 TI - Control of axonal growth and regeneration of sensory neurons by the p110delta PI 3-kinase. AB - The expression and function of the 8 distinct catalytic isoforms of PI 3-kinase (PI3K) in the nervous system are unknown. Whereas most PI3Ks have a broad tissue distribution, the tyrosine kinase-linked p110delta isoform has previously been shown to be enriched in leukocytes. Here we report that p110delta is also highly expressed in the nervous system. Inactivation of p110delta in mice did not affect gross neuronal development but led to an increased vulnerability of dorsal root ganglia neurons to exhibit growth cone collapse and decreases in axonal extension. Loss of p110delta activity also dampened axonal regeneration following peripheral nerve injury in adult mice and impaired functional recovery of locomotion. p110delta inactivation resulted in reduced neuronal signaling through the Akt protein kinase, and increased activity of the small GTPase RhoA. Pharmacological inhibition of ROCK, a downstream effector of RhoA, restored axonal extension defects in neurons with inactive p110delta, suggesting a key role of RhoA in p110delta signaling in neurons. Our data identify p110delta as an important signaling component for efficient axonal elongation in the developing and regenerating nervous system. PMID- 17846666 TI - The influence of temperature on the efficacy of polymerization of composite resin. AB - AIM: The purpose of this study was to investigate the effect of different temperatures on the efficacy of polymerization during the insertion of composite resin using different light curing units. METHODS AND MATERIALS: A total of 45 disc-shaped specimens were fabricated from Z250 composite resin (3M/ESPE, St. Paul, MN, USA) with 15 each prepared at three different temperatures (refrigerated to 5 masculineC, room temperature at 25 masculineC, and preheated to 37 masculineC). Each of these temperature-controlled specimen groups of 15 were then subdivided into three groups of five specimens, according to the type of curing light used to polymerize them. Curing lights included a conventional halogen light (QTH) in two modes (continuous and soft-start polymerization) and a light emitting diode (LED). The microhardness of the top and bottom surfaces of the specimens was determined using a Buehler Micromet II digital microhardness tester (Buehler, Dusseldorf, Germany). Data obtained was analyzed using two-way analysis of variance (ANOVA)/Post Hoc Tukey's test at a 0.05 significance level. RESULTS: As the temperature of composite resin increased, the top and bottom microhardness of the specimens also increased regardless of the type of polymerizing light used. The LED light produced a significantly better hardness on top and bottom surfaces of composite resin specimens polymerized at the three different temperatures. Effectiveness of cure at top and bottom surfaces of composite specimens was significantly reduced by using soft-start curing. CONCLUSION: The use of pre-warmed composite resins might help to improve polymerization of composite resin especially at the deeper areas of a restoration which could result in an increase in the expected life of a composite restoration. PMID- 17846667 TI - Bond strength of composite resin luting cements to fiber-reinforced composite root canal posts. AB - AIMS: The aim of this study was to compare the attachment of different composite resin luting cements to a fiber-reinforced composite (FRC) post with a semi interpenetrating polymer network polymer matrix. METHODS AND MATERIALS: Six different brands of composite resin luting cement stubs were applied on the surface of FRC post material and light-cured for 40 seconds. Shear bond strengths of luting cement stubs were measured using a universal testing machine. RESULTS: The differences in shear bond strengths between the cements were not statistically significant. CONCLUSION: All of the tested composite resin luting cements provided acceptable attachment to the tested FRC post. The tested FRC post material is suitable to use with different composite resin luting cements. PMID- 17846668 TI - A comparative evaluation of the effectiveness of an anorganic bone matrix/cell binding peptide with an open flap debridement in human infrabony defects: a clinical and radiographic study. AB - AIM: The development of biologic modalities designed to enhance bone regeneration and wound healing of specific periodontal sites continues to unfold. This is accomplished through the cell binding activity of Type-I collagen provided by a synthetic cell binding peptide (P-15) which is incorporated in a scaffold of anorganic bovine matrix (ABM). This combination is designed to facilitate the attachment, migration, and differentiation of cells. The objective of this study is to clinically and radiographically evaluate the effectiveness of the combination of ABM and P-15 (ABM/P-15) 'putty' during regenerative periodontal procedures. METHODS AND MATERIALS: A total of 20 interproximal intraosseous defects in 16 patients, (8 males, 8 females), age 22-48 years (mean 34.45) were recruited and divided equally into two experimental groups. Following open flap debridement (OFD), the defect sites in a test group were grafted with a bovine derived xenograft enriched with a cell binding peptide. The defect sites in a control group were treated with only OFD. Appropriate periodontal maintenance schedules were followed; at six months, clinical and radiographic assessments for soft tissue and hard tissue were performed for documentation and finalization of results. RESULTS: Statistical analysis using student paired 't' test analyses of the patient mean value from the 16 patients revealed the ABM/P-15 'putty' graft group demonstrated significantly better mean defect fill of 3.4 + 0.7 mm (70.5%) versus mean defect fill of 0.9 mm (17.33%) for defects treated with only OFD. Soft tissue findings showed significant differences among treatment with ABM/P-15 compared to OFD. CONCLUSIONS: These results indicate the use of P-15 synthetic cell binding peptide combined with ABM yields better clinical results in conjunction with OFD than with OFD alone. PMID- 17846669 TI - Risk factors for traumatic dental injuries in an adolescent male population in India. AB - AIM: The aim of this study was to determine the prevalence of traumatic injuries to the anterior teeth and evaluate the role of anatomic risk factors in the occurrence of such injuries in a group with an assumed behavior predisposing them to trauma. METHODS AND MATERIALS: The study population consisted of 370 male enrollees of the National Cadet Corps (NCC) in India. Risk factors such as the socioeconomic status (SES) of parents, lip coverage, incisor overjet, and the cause and nature of trauma to anterior teeth were recorded. The Chi-square test was used for testing the association between these factors. Increasing overjet was further analyzed using chi-square for linear trends. Variables found significant were subjected to logistic regression. RESULTS: A prevalence of 14.9% of traumatic injuries to anterior teeth was found in the study population with sports activities being the most common cause. Permanent maxillary central incisors were most commonly injured with injuries involving enamel and dentin being the most frequently observed. Increased overjet and inadequate lip coverage were significantly associated with the occurrence of trauma. With an odds ratio of 7.2 inadequate lip coverage was identified, using binary logistic regression, as the single most independent risk factor for the occurrence of traumatic injury to the maxillary anterior teeth. PMID- 17846670 TI - Idiopathic thrombocytopenic purpura presenting as post-extraction hemorrhage. AB - AIM: The aim of this article is to present a case of idiopathic thrombocytopenic purpura (ITP) in order to emphasize the importance of the clinical exam since the anamnesis leads to a diagnostic hypothesis of ITP. BACKGROUND: Acute ITP is considered an autoimmune disease characterized by the production of antibodies against platelets, antigens produced by a viral infection, or a platelet sparing drug combination. These antibodies adhere to platelets and are recognized and destroyed by the reticulo-endothelial system. Consequently, the platelet count gradually diminishes and is insufficient for the maintenance of primary hemostasis. REPORT: A 77-year-old woman presented with post-extraction intermittent bleeding. The physical examination revealed discoloration of the skin, multiple petechiae, hematomas, ecchymosis of the upper lip, bruises all over the body, gingiva that bled spontaneously, and a malformed blood clot at the extraction site of tooth #44. The hematological exams confirmed the hypothesis of ITP. The patient was immediately hospitalized in the Hematology Department of a local hospital and received platelet replacement, hydration, medication, and general care. After the spontaneous bleeding stopped, the malformed clot was removed using alveolar curettage along with a thorough cleaning of the extraction site with a 0.9% saline solution before suturing the wound and prescribing medication. After the sixth day of hospitalization, the patient presented with the following results: Hb: 12.3 mg/dL, Ht: 36.1%, and PC: 87,000 mm3. The patient was then discharged and was placed under outpatient follow-up care. SUMMARY: The importance of the clinical exam must be emphasized since the anamnesis leads to a diagnostic hypothesis of ITP and provides the dental surgeon with an opportunity to make important systemic alterations to improve the prognosis of a patient with ITP. PMID- 17846671 TI - Phenobarbital-induced gingival hyperplasia. AB - AIM: The aim of this article is to present a case of a phenobarbital-induced gingival hyperplasia (GH), discuss possible etiological mechanisms of drug induced GH, and to present a concise review of the literature. BACKGROUND: GH is a well-known complication associated with anticonvulsant phenytoin, antihypertensive calcium channel blockers, and immunosuppressant cyclosporine therapy. Sodium valproate and primidone has very rarely been found to cause GH. REPORT: An extremely rare case of phenobarbital-induced GH in a 28-year-old male patient who had received this drug for three years is presented. The histological examination of the lesion revealed a hyperplastic epithelium, epithelial acanthosis, and elongated rete ridges as well as obviously enhanced dense collagenous fibers and proliferation of fibroblasts. SUMMARY: Phenobarbital induced GH is a rare clinical entity which necessitates meticulous evaluation. However, it seems to show a benign behavior with reference to recurrence after surgical excision. PMID- 17846672 TI - Augmentation in two stages of atrophic alveolar bone prior to dental rehabilitation: a case report. AB - AIM: The aim of this report is to describe a significantly deficient case of alveolar bone that was managed by alveolar bone augmentation using a technique of distraction osteogensis and onlay bone grafting prior to dental implant placement. BACKGROUND: Injury to the teeth and alveolar ridge of the maxillary anterior region can cause a severe alveolar ridge deficiency resulting in ridge atrophy and maxillary retrognathism. The loss of these teeth and alveolar bone together with fibrotic scar formation can result in adverse changes of the interarch space, occlusal plane, arch relationship, and arch form which complicates rehabilitation and can compromise the esthetic outcome. While implant dentistry has become a new paradigm in oral reconstruction and replacement of missing teeth, ideal implant positioning can be compromised by inadequate alveolar bone in terms of bone height, width, and quality of the bone itself. Correction of osseous deficiencies with ridge augmentation allows ideal implant placement and creates a more natural soft tissue profile which influences crown anatomy and esthetics. REPORT: A 20-year-old female presented with a complaint of poor esthetics resulting from oral injuries incurred in a traffic accident six years previously. In addition to a mandibular parasymphyseal fracture, five maxillary anterior teeth and the most of the alveolar ridge were lost. Clinical examination revealed severe loss of bone in the maxillary anterior region, an absence of a labial sulcus, loss of upper lip support, and a slight over eruption of the mandibular anterior teeth. In preparation for dental implants a distraction osteogenesis surgical procedure was done to lengthen the height of the alveolar ridge. After a three-month healing period, the width of the residual ridge was found to be insufficient for implant placement. To correct this deficiency, a bone graft of a cortiocancellous block was harvested from the chin and fixed to the labial aspect of the ridge. To facilitate revascularization, small perforations were made in the cortical bone of the alveolar ridge at the recipient site before cancellous bone retrieved from the donor site was gently placed between the bone block and the ridge. The patient was then appropriately medicated and healing was uneventful. After three months, the width of the residual ridge was assessed to be adequate for endosseous implants. SUMMARY: The clinical result reported here has shown several procedures may be necessary for the rehabilitation of a trauma patient. Distraction osteogenesis per se may not always satisfactorily improve the anatomical alveolar anatomy but it has advantages over other methods of augmentation. It can improve the height and also expand the soft tissue for further bone grafting. Augmentation of the alveolar bone with an onlay bone graft often provides the desired gain of bone, allows for the ideal placement of dental implants, and improves any discrepancy between the upper and lower arches. PMID- 17846673 TI - Total impaction of deciduous maxillary molars: two case reports. AB - AIM: The purpose of this report is to present two cases of totally impacted maxillary deciduous molars, considered a rarity in dental practice. BACKGROUND: Primary tooth impaction is quite rare during the development of primary dentition. Various factors contribute to the impaction of a deciduous tooth, including anklyosis, congenitally missing permanent teeth, defects in the periodontal membrane, trauma, injury of the periodontal ligament, precocious eruption of the first permanent molar, defective eruptive force, or a combination of these factors. REPORTS: Case #1: An 18-year-old male presented with a complaint of spontaneous repetitious pain in the maxillary right premolar region. The maxillary right second premolar was clinically absent. Panoramic and periapical radiographs revealed an impacted second premolar close to the inferior wall of the maxillary sinus and an impacted deciduous molar deeply embedded in bone within the maxillary sinus. Case #2: A 14-year-old girl presented with a complaint of crowding of the maxillary teeth. The maxillary right second premolar and the maxillary permanent canines were clinically absent. A panoramic radiograph revealed an impacted maxillary right second premolar and an impacted deciduous molar embedded within bone close to the inferior wall of the maxillary sinus. SUMMARY: The total impactation of deciduous teeth is a rare condition, and few cases have been reported in the literature. The condition generally affects the mandibular second deciduous molar and the maxillary first deciduous least often. In this paper, two cases of totally impacted maxillary deciduous molars are reported. PMID- 17846674 TI - Maxillary canine impactions related to impacted central incisors: two case reports. AB - AIM: The purpose of this case report is to describe the combined surgical and orthodontic treatment of two cases with an impacted maxillary central incisor and canine in the same quadrant and to discuss the causal relationship between them. BACKGROUND: The most common causes of canine impactions are usually the result of one or more factors such as a long path of eruption, tooth size-arch length discrepancies, abnormal position of the tooth bud, prolonged retention or early loss of the deciduous canine, trauma, the presence of an alveolar cleft, ankylosis, cystic or neoplastic formation, dilaceration of the root, supernumerary teeth, and odontomas. Although impaction of the maxillary central incisor is almost as prevalent as impacted canines its etiology is different. The principal factors involved in causing the anomaly are supernumerary teeth, odontomas, and trauma. REPORTS: Case #1: A 10.5-year-old girl in the early mixed dentition stage presented with a chief complaint of the appearance of her anterior teeth. She had a Class I skeletal pattern and a history of trauma to the maxillary central incisors at age five with premature exfoliation. Radiographs revealed an impacted upper right central incisor in the region of the nasal floor, delayed eruption of the maxillary permanent central incisor, and the adjacent lateral incisor was inclined toward the edentulous space. Treatment was done in two stages consisting of surgical exposure and traction of the impacted central incisor and fixed orthodontic treatment. Case #2: An 11.5-year-old girl presented for orthodontic treatment with the chief complaint of an unerupted tooth and the appearance of her upper anterior teeth. She was in the late mixed dentition period with a Class III skeletal pattern along with an anterior cross bite with some maxillary transverse deficiency. The maxillary right canine and central incisor were absent, but the maxillary right deciduous canine was still present. Treatment included arch expansion followed by surgical exposure and traction of the impacted teeth and fixed orthodontic treatment. SUMMARY: This case report provides some evidence of a significant environmental influence of an impacted maxillary central incisor on the path of eruption of the ipsilateral maxillary canine. When an impacted maxillary central incisor exists, the maxillary lateral incisor's root might be positioned distally into the path of eruption of the maxillary canine preventing its normal eruption. Ongoing assessment and early intervention might help to prevent such adverse situations from occurring. PMID- 17846675 TI - A method of gauging dental radiographs during treatment planning for dental implants. AB - AIM: The goal of pre-surgical dental implant treatment planning is to position the optimum number and size of implant fixtures to achieve the best restorative results. The purpose of this article is to describe the use of radiographic imaging software to calibrate and measure anatomical landmarks to overcome inherent distortions associated with dental radiographs. The procedure along with its potential use as an adjunct to radiographic interpretation in routine clinical implant practice is presented. BACKGROUND: Diagnostic imaging is an essential component of implant treatment planning, and a variety of advanced imaging modalities have been recommended to assist the dentist in assessing potential sites for implants. Although technological advances have resulted in new imaging innovations for implant dentistry, dental radiography remains the most widely used tool for determining the quantity and quality of alveolar bone as it is a non-invasive procedure. However, the unreliable magnification factor associated with conventional radiographs remains a major problem when estimating the amount of bone available at the implant site. SUMMARY: This image measurement technique is capable of assessing the bone quantity by measuring the height and width of the alveolar crest for a specified region in a two dimensional plane in any direction related to the visible landmarks in the oral cavity. These measurements can be used by the clinician to select the type of implant and its position. Since there is no additional equipment or cost involved, the technique can be used as an important adjunct in implant practice. PMID- 17846676 TI - Dental trauma: restorative procedures using composite resin and mouthguards for prevention. AB - AIM: The aim of this article is to describe a step-by-step protocol for emergency care of a patient with a dentoalveolar injury in the anterior region of the mouth as well as the fabrication of a mouthguard to prevent future trauma. BACKGROUND: Dental trauma is one of the most serious oral health problems in active children and adolescents. Care of traumatized patients requires immediate initial emergency treatment followed by integrated procedures to restore damaged oral structures along with a subsequent trauma prevention strategy. Dentoalveolar injuries in the anterior region of the mouth are often characterized by tooth avulsion and coronal fracture. They are managed using procedures such as dental splinting, endodontic therapy with its unique characteristics, and restorative techniques to re-establish function and esthetics as well as protective mouthguards. REPORT: A 16-year-old male presented with avulsion of his maxillary central incisors as a result of a direct, unintentional impact with an opponent during a basketball game. The teeth had been stored in physiological serum immediately following the injury and the patient received immediate care. On clinical examination, the right central incisor was fractured at the incisal third of the crown but no bone fractures were found. The teeth were reimplanted and splinted. The fractured right central incisor was restored following endodontic treatment and a mouthguard was fabricated for the patient. SUMMARY: The dentist must be knowledgeable about the most efficient and suitable treatment for each traumatic scenario in order to provide appropriate care for dental injuries. Coordinated multi-disciplinary action is fundamental in the successful treatment of these injuries. The dental mouthguard is an effective device for protecting the teeth and supportive structures during physical activities and must be part of the protective equipment used by athletes. It is the responsibility of the dental professional to make parents, trainers, and athletic associations aware of the risks associated with physical activities without orofacial protection; this should encourage the proper use of all protective devices to prevent dentoalveolar injuries that compromise oral functions, esthetics, and increase the cost of healthcare. PMID- 17846678 TI - 'What is conservatism? Is it not adherence to the old and tried, against the new and untried?' Abraham Lincoln, 27 February, 1860. PMID- 17846677 TI - AAOMP case challenge: a pigmented lesion of the mandibular facial gingiva. AB - A 55-year-old white male was referred by his dermatologist for evaluation of an asymptomatic dark brown lesion on the mandibular facial attached gingiva. PMID- 17846680 TI - Evaluation of the triple tibial osteotomy. A new technique for the management of the canine cruciate-deficient stifle. AB - The triple tibial osteotomy (TTO) is a technique which combines the features of tibial tuberosity advancement and wedge osteotomy for the treatment of complete and partial cruciate ligament injuries in dogs. In this paper, the technique is described and the results of a prospective study of 64 consecutive cases are presented. TTO provided a satisfactory clinical outcome in a very high percentage of cases. The technique is relatively easy to learn and has a low post-operative complication rate. PMID- 17846679 TI - The role of bone morphogenetic proteins in articular cartilage development, homeostasis and repair. AB - Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily of secreted ligands. BMPs regulate a diverse range of developmental processes during embryogenesis and postnatal development, and control the differentiation of several musculoskeletal tissues including bone, cartilage, tendon and ligaments. The ability of BMPs to modulate the phenotype of cells in these tissue lineages suggests that these factors could be valuable for musculoskeletal tissue regeneration. In fact, BMPs-2 and -7 are already in clinical use for bone regeneration. This review addresses the signaling mechanisms by which BMPs regulate cellular processes, the role of BMPs in articular cartilage development and joint formation, and the data that supports the use of BMPs for in vitro phenotypic support of articular chondrocyte cultures, chondrogenic differentiation of mesenchymal stem cells (MSCs) and articular cartilage repair. Given the documented importance of BMP activity for normal joint formation, articular cartilage development and maintenance, the chondrogenic activity of BMPs when applied to MSC cultures and the encouraging outcomes of several in vivo cartilage repair studies, BMP therapies hold considerable promise for effective cartilage repair and/or regeneration. Future advances in the control of BMP elution from biocompatible matrices and prolonged, dose-controlled BMP expression by genetically engineered cells should substantially improve cartilage repair strategies using BMPs and similar chondro-protective proteins. PMID- 17846681 TI - Geometric implications of the tibial wedge osteotomy for the treatment of cranial cruciate ligament disease in dogs. AB - The tibial wedge osteotomy (TWO), a procedure that reduces the tibial plateau slope, has become an established surgical technique for the treatment of cranial cruciate ligament injuries in dogs, yet variation from the desired postoperative tibial plateau slope of 6 degrees has been noted. The objectives of this study were to investigate the geometric implications of this procedure and to identify factors that affect the postoperative angles. The records of 35 consecutive cases that had a TWO performed were reviewed and comparisons were made between the alignment of the cortices and level of the osteotomy using duplicated tracings of a preoperative radiograph. The existing method for calculating the size of wedge to be removed was found to result in a postoperative slope greater than the expected 6 degrees. Our results indicate that the desired postoperative angle is more likely to be achieved if the cranial cortices are aligned and the osteotomy is performed proximally. PMID- 17846682 TI - Evaluation of compression generated by self compressing Orthofix bone pins and lag screws in simulated lateral humeral condylar fractures. AB - A simulated lateral humeral condylar fracture was created in each of the 52 humeri collected from 26 dogs. One humerus from each pair was stabilized with a 2.0 mm cortical bone screw which was inserted in lag fashion. The other humerus from each pair was stabilized with a 2.2 mm threaded diameter Orthofix pin inserted across the condyle. Prior to each repair, an antirotational K-wire was placed and then the Pressurex Sensitive film was inserted in the osteotomy site in order to determine the compressive pressure (MPa), compressive force (KN), and area of compression (cm(2)) achieved during fixation. The maximum insertional torque achieved before stripping was measured for each implant. The mean compression generated by insertion of a 2.0 mm lag screw was 20.36 +/- 1.51 MPa compared to 18.88 +/- 1.76 MPa generated by a 2.2 mm Orthofix pin (p < 0.003). The mean area of compression generated by insertion of a 2.0 mm lag screw was 2.39 +/- 1.29 cm(2), compared to 1.16 +/- 0.84 cm(2) generated by insertion of a 2.2 mm Orthofix pin (p < 0.0001). The mean compressive force (compression x area compressed) generated by insertion of a 2.0 mm lag screw was 4.96 +/- 2.90 Kn, compared to 2.20 +/- 1.65 Kn generated by insertion of a 2.2 mm Orthofix pin (p < 0.0001). The mean insertion torque to failure for the lag screws was 0.49 +/- 0.07 NM, compared to 0.91 NM +/- 0.18 NM generated by the Orthofix pins (P < 0.0001). Both repair methods are likely to be acceptable for the repair of similar fractures in small breed dogs. PMID- 17846683 TI - Rotating dome trochleoplasty: an experimental technique for correction of patellar luxation using a feline model. AB - The purpose of this study was to compare a trochlear block recession to a rotating dome trochleoplasty, a novel technique for the correction of patellar luxation in small animals. Twenty-eight limbs were used from 14 feline cadavers. With the stifles in flexion and extension, computed tomography was utilized to compare width and depth of the trochlea, medial trochlear ridge height, trochlear articular surface area preserved, patellar contact articular surface area, patellar area covered by the trochlear ridges and patellar tilt angle. The results of this study demonstrated that a rotating dome trochleoplasty is superior to a trochlear block recession with regard to medial trochlear height, trochlear width, trochlear depth and trochlear surface area preservation. The results of this study support further biomechanical evaluation of this technique which eventually may lead to clinical trials. PMID- 17846684 TI - Phenotypic maintenance of articular chondrocytes in vitro requires BMP activity. AB - Articular chondrocytes are phenotypically unique cells that are responsible for the maintenance of articular cartilage. The articular chondrocytic phenotype is influenced by a range of soluble factors. In particular, members of the bone morphogenetic protein (BMP) family support the articular chondrocytic phenotype and stimulate synthesis of cartilaginous matrix. This study was carried out to determine the importance of BMPs in supporting the differentiated phenotype of articular chondrocytes in vitro. Exogenous BMP-2 supported expression of collagen type II and aggrecan in monolayer chondrocyte cultures, slowing the dedifferentiation process that occurs under these conditions. In contrast, BMP-2 had little effect on expression of these genes in three-dimensional aggregate cultures. Endogenous BMP-2 expression was lost in monolayer cultures, coincident with the down-regulation of collagen type II and aggrecan mRNAs, whereas BMP-2 mRNA levels were stable in aggregate cultures. Antagonism of endogenous BMP activity in aggregate cultures by Noggin or a soluble form of the BMP receptor resulted in reduced expression of collagen type II and aggrecan mRNAs, reduced collagen type II protein and sulfated glycosaminoglycan (GAG) deposition into the aggregate matrices and reduced secretion of GAGs into the culture media. These results indicate that endogenous BMPs are required for maintenance of the differentiated articular chondrocytic phenotype in vitro. These findings are of importance to cell-based strategies designed to repair articular cartilage. Articular chondrocytes require conditions that will support endogenous expression of BMPs to maintain the specialized phenotype of these cells. PMID- 17846685 TI - Temporomandibular joint ankylosis in cats and dogs. A report of 10 cases. AB - Temporomandibular joint (TMJ) ankylosis is characterized by difficulty or inability to open the mouth. The ankylosis may be articular ('true') or extra articular ('false'). Clinical signs, radiographic studies, treatment and follow up are presented in a retrospective study involving five cats and five dogs. The findings were compared with TMJ ankylosis in humans. CT imaging with three dimensional reconstruction proved to be of great value in determining the extent of the abnormalities and helped with preoperative planning. Articular TMJ ankylosis occurred in six animals and extra-articular TMJ ankylosis was found in the other four cases. In three cats and in three dogs, the TMJ ankylosis was trauma related; the remaining patients were diagnosed with a tumour. Resection of ankylosing tissue in false ankylosis or gap arthroplasty in true ankylosis was successful in all of the trauma induced cases. In the two cats, with tumour related ankylosis, the ankylosis was caused by an osteoma and resection had a good prognosis, whereas the two dogs had to be euthanatized. PMID- 17846686 TI - Stifle joint luxation in the dog and cat: the use of temporary intraoperative transarticular pinning to facilitate joint reconstruction. AB - Multiple ligament injuries of the canine and feline stifle joint which result in luxation are uncommon. Two cats and one dog, that had sustained such a joint injury were surgically treated. A rupture of the cranial and caudal cruciate ligaments, and at least one collateral ligament was observed in all of the three animals. Prosthetic reconstruction was used, as previously described, in combination with a novel technique of intraoperative placement of a temporary trans-articular pin (TTP) to maintain intra-operative anatomical reduction. TTP placement facilitated maintenance of joint alignment during surgical reconstruction and aided appropriate tensioning of the prosthetic sutures, preventing collapse of femorotibial joint compartments. The TTP was removed prior to closure of the joint allowing immediate post-operative joint mobilisation. Based on assessment by their owners, all the animals made a complete recovery. TTP was considered a relatively simple and effective adjunctive aid for surgical treatment of traumatic luxation of the stifle joint. PMID- 17846687 TI - Patellar luxation as a complication of surgical intervention for the management of cranial cruciate ligament rupture in dogs. A retrospective study of 32 cases. AB - This retrospective study identified 32 cases of patellar luxation which occurred as a complication of surgical intervention for cranial cruciate ligament rupture (CCLR). The complication was recorded mostly in larger (>/=20 kg) dogs with the Labrador Retriever being the most common breed. The complication followed extra capsular, intra-capsular and tibial plateau levelling surgery. The mean time from CCLR surgery to the diagnosis of patellar luxation was 14 weeks. The incidence of patellar luxation occurring as a complication of surgical intervention for CCLR was 0.18% of all CCLR corrective procedures. Corrective surgery for patellar luxation was successful in 79% of stifles. The patellar reluxation rate was significantly lower (p = 0.0007) when at least one corrective osteotomy (tibial tuberosity transposition, femoral trochlear sulcoplasty or tibial plateau levelling osteotomy with tibial axial re-alignment) was performed (35%), compared to when corrective osteotomy was not performed (100% patellar reluxation rate). When performing corrective surgery for patellar luxation following CCLR surgery, at least one corrective osteotomy should be performed in order to reduce the patellar reluxation rate. The correction of patellar luxation following surgery for CCLR is challenging and carries a significant rate of failure. PMID- 17846688 TI - Retrograde placement of a novel 3.5 mm titanium interlocking nail for supracondylar and diaphyseal femoral fractures in cats. AB - Twenty-four simple or comminuted supracondylar and diaphyseal femoral fractures in cats, which had been treated by retrograde insertion of a new 3.5 mm titanium interlocking nail (IN) from the intercondylar notch, were evaluated between June 2000 and October 2004 at the Ecole Nationale Veterinaire d'Alfort. Patient data (species, breed, weight, and age), fracture characteristics, details of the surgery, post-operative complications and radiographic follow-up were recorded. The mean body weight was 3.75 kg and the cats ranged in age between four and 66 months (mean 29 months). The IN had a diameter of 3.5 mm and a length of 100, 109 or 119 mm, and were all fixed in a static position (two screws in seven cats, three screws in 10 cats and four screws in seven cats). Cerclage wires were used in seven cats and an autogenous bone graft was used in two cats. Screw or nail breakage were not recorded. Nineteen fractures healed without any complications, three cats died during the post-operative period from unknown causes, and two cats showed delayed bone healing. Twenty cats were considered to have an excellent limb function at one month. One cat with a sciatic injury was non weight bearing for several months. Radiographic signs of degenerative joint disease of the stifle joint were not observed except in the cat with the sciatic nerve injury. The results of this study suggest that this new 3.5 mm titanium IN can be introduced from the intercondylar notch and be used in static fixation mode to stabilize supracondylar and diaphyseal femoral fractures in cats. PMID- 17846689 TI - Surgical treatment of simple syndactylism with secondary deep digital flexor tendon contracture in a Basset Hound. AB - A five-month-old, female Basset Hound was presented for lameness associated with a fused 3rd and 4th digital pad on the left hind limb (simple incomplete syndactyly), and secondary contracture of the deep digital flexure tendon of the 3rd and 4th digit. An onychectomy of the third phalanx of the third and fourth digits was performed. Following the operation, the dog gained good use of the affected limb for one month until intermittent non-weight bearing lameness developed. A second surgery was performed six months later, partially removing the second phalanx of digits three and four. Follow-up reports indicate that the dog is doing well and is without lameness. This is the first report of deep digital flexor tendon contracture and surgical treatment of this complication in canine simple syndactylism. PMID- 17846690 TI - Luxation of the long digital extensor tendon as a complication to Tibial Plateau Levelling Osteotomy. A presentation of four cases. AB - Cranial cruciate ligament disease in dogs is frequently treated with Tibial Plateau Levelling Osteotomy (TPLO). Herein we describe four cases of dogs presenting with sudden lameness in the operated leg one to 12 months post TPLO surgery. On examination, all of the dogs had a luxation of the long digital extensor tendon (LDE) resulting from the TPLO surgery. All of the dogs underwent revision surgeries. The LDE tendon was either secured in its normal position or transected, and a tenodesis was performed. The dogs recovered well after surgery and lameness was resolved in all four cases. PMID- 17846691 TI - Surgical treatment of a vertebral fracture associated with a haematogenous osteomyelitis in a dog. AB - A seven-month-old Rottweiler was referred for a diagnosed femoral neck fracture and a suspected vertebral fracture. The simplified neurological examination revealed an acute paraplegia. A discospondyilitis associated with a pathologic fracture of Th11 and a spinal compression, and a haematogenous epiphysitis of the femoral neck were diagnosed based on radiographic and computed tomographic examinations. The vertebral fracture was stabilised using screws and polymethylmetacrylate with gentamycin by a lateral intercostal approach. The dog was able to walk seven days later. A femoral head and neck ostectomy was performed two weeks later. Staphylococcus intermedius was isolated from both sites, which confirmed the diagnosis. The dog was treated with cephalexin (30 mg/kg/d) for six weeks. A telephone interview with owners indicated that no more clinical signs were present four months after the second surgery. Discospondylitis associated with haematogenous osteomyelitis has only been reported in two cases. Paraplegia is an unusual clinical presentation for discospondylitis. The lateral approach (which allowed a direct access to the infected site) and the technique (screws associated with antibiotic-impregnated cement) are unique for surgical treatment of discospondylitis. Although applying cement to an infected area may pose a risk, antibiotic-loaded cement is successfully used in the treatment of chronic osteomyelitis in humans. PMID- 17846692 TI - Ulnocarpal arthrodesis for the treatment of radial agenesis in a dog. AB - Forelimb deformity caused by radial agenesis was diagnosed in a one-year-old Shih Tzu dog. In contrast to most of the previously reported cases of radial agenesis, the humeroulnar joint was inherently stable. The deformity was treated by means of a one-stage ulnocarpal arthrodesis with the application of an eight hole dorsolateral arthrodesis bone plate and autogenous corticocancellous bone graft from the ilial wing. Radiographic evaluation at the eighth and sixteenth post operative week showed evidence of union of the arthrodesis. At sixteen weeks post operatively, the dog had much improved limb function. In humans afflicted with radial agenesis, ulnocarpal arthrodesis is used to restore forearm function by minimizing pain and decreasing the magnitude of angular deformity and instability at the level of the ulnocarpal joint. However, to our knowledge, this is the first report of treatment of radial agenesis in the dog by means of a one-stage, ulnocarpal arthrodesis. PMID- 17846693 TI - Limb alignment of pes valgus in a giant breed dog by plate-rod fixation. AB - A 2-year-old, female, neutered Newfoundland presented with pelvic limb lameness due to a distal tibial valgus deformity. A left distal fibula ostectomy and disto medial tibial cuneiform ostectomy were performed with reduction and stabilisation using plate-rod internal fixation. Following surgical correction of the deformity the dog regained good functional mobility of the limb. PMID- 17846694 TI - Bilateral pes valgus in an Anatolian Sheepdog. AB - A 15-month-old, male, Anatolian Sheepdog weighing 45 kg, was admitted with uneven stance in both hindlegs, a condition it had had since the age of six months. Radiographs of both hindlimbs revealed lateral deviation of 26 degrees in the distal metaphysis of the left tibia and 32 degrees in the distal metaphysis of the right tibia. Corrective osteotomy was used to treat the deformity. Both tibias were aligned with the closed wedge osteotomy and a suitably curved plate was placed on both bones. In the assessment prior to the removal of both plates, it was determined that a valgus deformation of 6 degrees was still present. However, this did not affect the gait, nor did it have an abnormal effect on the cosmetic appearance. It was concluded that if corrective osteotomy is performed before any degenerative changes have taken place, the outcome will be successful. PMID- 17846695 TI - Avulsion of the triceps tendon insertion in a cat. AB - Avulsion of the insertion of the triceps tendon, which had a pre-existing tendinopathy, is described in a cat. The tendon was re-attached to the olecranon and the repair was immobilised using a type la trans-articular external skeletal fixator. The treatment was successful, however, mild and intermittent lameness persisted. Although it is an uncommon condition in small animals, the diagnosis should be based on careful clinical and radiographic examination. PMID- 17846696 TI - Adult and peer involvement in help-seeking for depression in adolescent population: a two-year follow-up in Finland. AB - Help-seeking among adolescents and adults is often perceived as a process involving only the health care system and the individual suffering from psychiatric symptoms. The present study attempted to create a model of help seeking also including members of adolescents social networks. A prospective follow-up design included a school-based survey on all ninth grade students (mean age 15.5) during the academic year 2002-2003 in two Finnish towns (N = 3,278; response rate 94%); and a follow-up conducted two years later (N = 2,080; response rate 63%). The respondents were assessed for current depression and help seeking for depression and other mental health problems each time. In the follow up they were asked if they felt that they need help for depression and if their mother, father, sibling, peers, boy- or girl-friend or teacher had been worried about changes in their mood or behaviour. The associations of perceived need for help, help-seeking behaviour and concerns of different people, with depression at baseline were studied. Stepwise logistic regression models were computed to find the best predictors for help-seeking for depression. One third of the adolescents meeting R-BDI-13 criteria for depression at baseline still perceived a need for help for depression two years later but only a fifth of them had sought professional help. Depression at baseline was significantly associated with concerns about changes in mental health or behaviour among parents and significant others; and the concerns of mother, peers and teacher were among the best predictors of recent help-seeking for depression. To ensure adequate intervention for depressed adolescents without a social network capable of prompting referral, routine screening for depression should be applied in primary health care services and specialized services for adolescents. PMID- 17846697 TI - To what extent may the association between immigrant status and mental illness be explained by socioeconomic factors? AB - BACKGROUND: Immigrants in Sweden have a higher rate of mental illness than the native Swedes. This study investigated to what extent the association between immigrant status and mental illness can be explained by a different distribution of known risk factors for impaired mental health between groups of immigrants and persons born in Sweden. METHODS: The study is based on data from the Swedish PART study, designed to identify risk factors for, and social consequences of, mental illness. The study population consists of a random sample of 10,423 Swedish citizens, whereof 1,109 were immigrants. The data was collected in the year 2000. The immigrants were divided into three groups based on country of origin (Scandinavians born outside Sweden, Europeans born outside Scandinavia, non Europeans). The occurrence of mental illness among immigrants and native Swedes were compared not adjusting and adjusting for indicators of socioeconomic advantage/disadvantage (education, income, labour market position, etc). Mental illness was approximated with the WHO (ten) wellbeing index scale and depressive symptoms were measured with the major depression inventory scale (MDI). RESULTS: Immigrants' excess risk for low subjective wellbeing was completely accounted for by adjustment for known risk factors in all the immigrant groups. However, social economic disadvantages could not account for the non-European immigrants' higher prevalence of depression (MDI), although the increased relative risk found in univariate analyses was substantially reduced. CONCLUSIONS: The findings in this study suggest that the association between immigrant status and mental illness appears above all to be an effect of a higher prevalence of social and economic disadvantage. PMID- 17846698 TI - Visual impairment in persons with psychotic disorder. AB - BACKGROUND: Persons with psychotic disorder may have poorer visual acuity (VA). The aim of the study is to investigate in a general population the prevalence of impaired habitual VA and self-reported difficulties in vision among persons with different psychotic disorders. METHOD: A nationally representative sample of 6,663 persons aged 30 or older whose binocular VA for distance and for near vision was measured with current spectacles, if any. Diagnostic assessment of DSM IV psychotic disorders used both SCID interview and case note data. Life-time ever diagnoses of psychotic disorders were classified into schizophrenia, other non-affective psychotic disorders and affective psychoses. RESULTS: After adjusting for age and sex, schizophrenia was associated with significantly increased odds of having visual impairment for distance (OR 5.04, P < 0.0001) and for near vision (OR 6.22, P < 0.0001), while other psychotic disorders were not. Self-reported problems in VA were more common in persons with schizophrenia and other non-affective psychotic disorders than in the remaining study sample. Only 43.9% of persons with schizophrenia, compared with 69.7% in the total sample (chi(2) = 13.79, d.f. 1, P = 0.0002), had had their vision examined during the 5 years before the VA measurement. CONCLUSIONS: Because persons with schizophrenia attend vision examinations substantially less frequently than others, and their vision is notably weaker, regular ocular evaluations should be included in physical health monitoring in psychotic disorders. PMID- 17846699 TI - Self-esteem and violence: testing links between adolescent self-esteem and later hostility and violent behavior. AB - This study investigated the relationship between self-esteem in adolescence and later violent offending and hostility via self- and other-report, examining data from a birth cohort of over 1,000 New Zealand young adults studied to age 25. Lower levels of self-esteem at age 15 were related to greater risks of violent offending and higher levels of hostility at ages 18, 21, and 25. Adjustment for potentially confounding factors reduced the strength of the associations between self-esteem at age 15 and both self- and other-reported violent offending and other-reported hostility at ages 18, 21, and 25 to statistically non-significant levels. The association between self-esteem at age 15 and later self-reported hostility remained statistically significant, but was small in magnitude. A similar pattern of results were obtained using self-esteem at age 10 as the predictor variable in place of the age 15 measure. In addition, a persistent association was found between unstable high self-esteem and self-reported violent offending. The results suggest that self-esteem level plays a limited role in the understanding of violent behavior. PMID- 17846700 TI - Heavy metal accumulation in hot water tanks in a region experiencing coal waste pollution and comparison between regional water systems. AB - In 2000, a coal slurry impoundment failure in Martin County, Kentucky, caused concerns about contaminants entering municipal water supplies. Water samples taken from impacted and reference area hot water tanks often exceeded US EPA drinking water guidelines. Concentrations of As, Cd, Cr, Cu, Fe, Mn, and Pb had maxima of 119; 51.9; 154; 170,000; 976,000; 8,710; and 12,700 microg/L, respectively. Significantly different metal accumulation between counties indicated this procedure's utility for assessing long-term municipal water quality. Correlations between metal concentrations were strong and consistent for As, Ba, Cd, Cr, Co, and Fe indicating that some metals accumulate proportionally with others. PMID- 17846701 TI - Fucus spp. as a mercury contamination bioindicator in costal areas (Northwestern Portugal). AB - Mercury has been considered as one of the most important pollutants in coastal and estuarine areas. Efforts have been made to detect, as early as possible, the effects of this and other metals in several species. Macroalgae, particularly Fucus spp., have been widely used as biomonitors of metal pollution. In this study, three Fucus species (F. spiralis, F. vesiculosus and F. ceranoides) were collected from several sampling sites in Portugal. The concentrations of mercury were determined in three structural parts (holdfast, stipe and receptacles). Two different techniques were used to determine mercury concentrations. Almost all mercury concentrations (in sediments and in water) were below national and international standards. Mercury concentration in the specimens (0.012-0.061 microg g(-1) for receptacles, 0.028-0.221 microg g(-1) for stipe and 0.029-0.287 microg g(-1) for holdfast) was always higher that those obtained for the sediment (0.001-0.112 microg g(-1)). With few exceptions the contrary was found for receptacles. In general, a good agreement between concentrations of mercury in sediment and Fucus was found. The results indicate that Fucus accumulate mercury and may be a suitable species for use in risk assessment for coast and estuarine areas, by providing valuable information regarding the levels of mercury that will be available for the consumers of Fucus spp. PMID- 17846702 TI - Mechanical properties of polypropylene mesh used in pelvic floor repair. AB - The aim of this study was the comparison of the stiffness of different meshes under two types of mechanical tests. Five different mesh types were mechanically tested. The methods used consisted on uniaxial tension test (tensile stiffness) and tape ring tests, experimental continuous compression of the mesh loops (flexural stiffness). The most significant difference of tensile stiffness behaviour appears between Aris and TVTO. From the analysis of the experimental data, we divided the flexural stiffness, in two main groups. The first group includes Auto Suture and Aris meshes. The two meshes seem to have a similar flexural behaviour. The second group includes TVTO, Uretex and Avaulta. The difference between these two groups is clearly evident comparing TVTO and Aris. This study shows that there are significant differences on the mechanical properties between urogynecology meshes. PMID- 17846703 TI - Choice of mesh for laparoscopic ventral hernia repair. AB - BACKGROUND: Surgical treatment of ventral hernias has changed dramatically over the past decades by the introduction of laparoscopy and prosthetic biomaterials for reinforcement of the abdominal wall. There are many meshes available on the market for laparoscopic ventral hernia repair (LVHR), and new meshes are introduced regularly. Experimental and clinical documentation for safety and efficacy are, however, often not available for the clinician. The choice of mesh may therefore be difficult in clinical practice. We present a review of the current literature regarding safety measures such as adhesions, fistulas, and infections as well as the available data on pain, recurrence, mesh shrinkage, and seroma formation after LVHR. METHODS: The literature was searched systematically using PubMed/MEDLINE and EMBASE for controlled studies, prospective descriptive series and retrospective case series. RESULTS: The literature clearly points in the direction of very few mesh-related complications after LVHR. Experimental studies and theoretical considerations may argue for using a covered mesh, i.e., a composite mesh, or ePTFE for LVHR in humans, although it is important to stress that there are no human data at the moment to support this. Concerns about using pure polypropylene mesh in the intraperitoneal position may be re-evaluated with the experience of lightweight macropore meshes from open surgery in mind. There is a tendency towards greater shrinkage in ePTFE-based meshes but no differences seems to exist between different mesh materials in other relevant outcome parameters from clinical series. CONCLUSIONS: The literature cannot give general recommendations for choice of mesh based on randomized controlled trials. The final choice of mesh for LVHR will therefore typically be based on surgeons' preference and cost while we await further data from randomized controlled clinical trials. PMID- 17846705 TI - Induction of axenic culture of Arthrospira (Spirulina) platensis based on antibiotic sensitivity of contaminating bacteria. AB - Arthrospira platensis SAG 21.99 and the isolated bacteria (Halomonas spp., Staphylococcus sp., etc.) from the culture of A. platensis SAG 21.99 were treated with five antibiotics to determine the minimal lethal concentrations. The combination of a washing step and a consecutive treatment with antibiotics, imipenem (100 microg ml(-1)), neomycin (100 microg ml(-1)) and cycloheximide (20 microg ml(-1)), treatment step was highly effective in eliminating bacteria. An axenic culture of A. platensis SAG 21.99 could be induced within 3 days using this method. This technique is a simple and rapid method for obtaining axenic cultures of filamentous cyanobacteria. PMID- 17846704 TI - Weekly docetaxel, zoledronic acid and estramustine in hormone-refractory prostate cancer (HRPC). AB - Treatment options for patients with hormone refractory prostate cancer (HRPC) showed unsatisfactory outcomes. Docetaxel-based combinations could offer more promising and tolerated results. A phase II trial was conducted with the combination of zoledronic acid, docetaxel and estramustine. Eligibility consisted of metastatic prostate adenocarcinoma with objective progression or rising prostate specific antigen levels (PSA) despite androgen deprivation therapy. Zoledronic acid was given at a dose of 4 mg on day 1, docetaxel (25 mg/m2) on days 1, 8 and 15, and estramustine orally at 140 mg two times daily on days 1 to 21 of a 28-day cycle. Twenty-seven patients were enrolled between October 2002 and November 2004. Median age was 68 years (53-83 years). A total of 124 cycles were administered with a median of 4.6 cycles per patient (1-8 cycles). The major toxicities were grades 1 to 3 anemia (55%), fatigue (15%), alopecia (11%) and hypocalcemia (11%). Two patients presented with deep venous thrombosis and died from pulmonary embolism. Another third patient died from Stevens-Johnson syndrome and grade 4 hepatic toxicity. Out of the 25 patients assessed for efficacy, 13 (52%) had a biologic response (>50% PSA decline). Three (21%) patients among the 14 with measurable disease had objective response: 1 complete response (CR) and 2 partial responses (PR). Response duration was 2 months for PR and 4 months for CR. A total of 12 patients (48%) experienced clinical benefit with pain reduction. This combination seemed effective; however toxic deaths especially from venous thrombosis counterbalanced the advantage of this regimen. PMID- 17846706 TI - Kinetic and functional analysis of the heparin-binding domain of fibronectin. AB - We have previously shown that the heparin-binding domain of fibronectin (FN-HBD) enhances cell adhesion and proliferation of osteoblasts. Here we demonstrated that FN-HBD binds to heparin with a K(D) of 5 microM. Although, FN-HBD itself produces a modest effect on cell adhesion in the absence of central cell-binding domain (CCBD), FN-HBD significantly enhances cell adhesion and spreading activities by a cooperative mechanism of CCBD in MG63 cells (P < 0.05). PMID- 17846707 TI - Hematopoietic reconstitution of CD34+ cells grown in static and stirred culture systems in NOD/SCID mice. AB - The hematopoietic reconstitution of cord blood (CB) CD34(+)cells grown in static and stirred system was studied. Static cultures were better than stirred cultures for cell expansion. Engraftment of stirred-culture hematopoietic stem cells (HSCs) was higher than static-culture HSCs. Stirred-culture HSCs had better multilineage reconstitution ability and colony-forming ability than static culture HSCs. Static cultures thus favor the expansion of HSCs and stirred cultures are more effective in preserving functional HSCs. PMID- 17846708 TI - Dissecting cellular components of the secretory pathway in filamentous fungi: insights into their application for protein production. AB - Studies on protein production using filamentous fungi have mostly focused on improvement of the protein yields by genetic modifications such as overexpression. Recent genome sequencing in several filamentous fungal species now enables more systematic approaches based on reverse genetics and molecular biology of the secretion pathway. In this review, we summarize recent molecular based advances in our understanding of vesicular trafficking in filamentous fungi, and discuss insights into their high secretion ability and application for protein production. PMID- 17846709 TI - Triethylene tetramine, a novel ligand of G-quadruplex, induces senescence of MCF 7 cells. AB - Interference with telomerase and telomere maintenance is emerging as an attractive target for antitumor therapies. Ligands stabilizing G-quadruplexes have the potential to interfere with telomere replication by blocking the elongation of telomeres in tumors. Here, we report that long-term treatment with triethylene tetramine (TETA), at 50 or 100 microM, induced marked cellular senescence phenotypes accompanied by increased time of population doubling of MCF 7 cells. Cyclin-dependent kinase inhibitors, including p53 and p21, were also upregulated in TETA-treated MCF-7 cells. TETA is therefore as novel ligand of G quadruplex and can induce tumor senescence; it is a promising material for tumor treatment. PMID- 17846710 TI - Current issues regarding skin substitutes using living cells as industrial materials. AB - There have been many clinical cases of skin treatment using cultured epidermis, as established by H. Green in 1975. This procedure, famously, made it possible to make artificial skin using living cells. Permanent coverage for injury wounds was achieved with cultured epidermis made from autologous cells. Recently, many types of skin substitutes using living cells have been used clinically. The extent to which cellular skin substitute techniques established through basic research can be incorporated into general medical treatment is a controversial issue at present. Some techniques are at the commercializing stage as medical materials. Cultured epidermis, as described above, cultured dermis, and skin equivalent are already well established. In this article, we will describe the current issues regarding skin substitutes using living cells. PMID- 17846711 TI - Building artificial humans to understand humans. AB - If we could build an android as a very humanlike robot, how would we humans distinguish a real human from an android? The answer to this question is not so easy. In human-android interaction, we cannot see the internal mechanism of the android, and thus we may simply believe that it is a human. This means that a human can be defined from two perspectives: one by organic mechanism and the other by appearance. Further, the current rapid progress in artificial organs makes this distinction confusing. The approach discussed in this article is to create artificial humans with humanlike appearances. The developed artificial humans, an android and a geminoid, can be used to improve understanding of humans through psychological and cognitive tests conducted using the artificial humans. We call this new approach to understanding humans android science. PMID- 17846712 TI - Optimization and safety of the intra-aortic balloon pumping balloon catheter. AB - Tokai Medical Products developed an intra-aortic balloon pumping (IABP) balloon catheter with the following unique characteristics: the balloon can be applied to any patient irrespective of their physical size, and is therefore suitable for Japanese patients of small stature; a long soft tip is used, which is designed to avoid damage to blood vessels; the size of the catheter is reduced to 7 Fr, and the catheter can be used as a multifunctional balloon catheter, such as the Yoshioka type, that allows simultaneous percutaneous coronary intervention (PCI). The safety of this catheter has been proven in scientific studies. In this review, we report the development of our IABP balloon catheter and give an outline of its characteristics. PMID- 17846714 TI - Development of a miniature motor-driven pulsatile LVAD driven by a fuzzy controller. AB - We have been developing a small, lightweight motor-driven pulsatile left ventricular assist device (LVAD) with a ball screw. The motor-driven LVAD consists of a brushless DC motor and a ball screw. The attractive magnetic force between Nd-Fe-B magnets (with a diameter of 5 mm and a thickness of 1.5 mm) mounted in holes in a silicone rubber sheet (thickness 2 mm) and an iron plate adhered onto the a diaphragm of the blood pump can provide optimum active blood filling during the pump filling phase. The LVAD has a stroke volume of 55 ml and an overall volume of 285 ml; it weighs 360 g. The controller mainly consists of a fuzzy logic position and velocity controller to apply doctors' and engineers' knowledge to control the LVAD. Each unit of the controller consists of a functionally independent program module for easy improvement of the controller's performance. The LVAD was evaluated in in vitro experiments using a mock circulation. A maximum pump outflow of 5.1 l/min was obtained at a drive rate of 95 bpm against an afterload of 95 mmHg, and active filling using the attractive magnetic force provided a pump output of 3.6 l/min at a drive rate of 75 bpm under a preload of 0 mmHg. The operating efficiency of the LVAD was measured at between 8% and 10.5%. While the LVAD can provide adequate pump outflow for cardiac assistance, further upgrading of the software and improvement of the blood pump are required to improve pump performance and efficiency. PMID- 17846713 TI - Use of fluorescent quantum dot bioconjugates for cellular imaging of immune cells, cell organelle labeling, and nanomedicine: surface modification regulates biological function, including cytotoxicity. AB - With the development of nanotechnology, nanoscale products that are smaller than several hundred nanometers have been applied to all areas of science and technology. Nanoscale products, including carbon nanotubes, fullerene derivatives, and nanocrystal quantum dots (QDs), are wide spread as novel tools in various fields, not only in materials engineering, electronics, plastics, and the automobile and aerospace industries, but also in molecular biology and medicine. At present, QDs have been widely used in biological and medical studies because of their superior photoemission and photostability. Although the physical and chemical properties of QDs have been circumstantially investigated, little is known about any harmful effects of QDs on human health. Here we report on the toxicity and biological behavior of QDs in vitro and in vivo. The toxicity of the core constituent chemicals such as cadmium and selenium has been identified. Recently, the surface molecules surrounding QDs have been intensively investigated. Accumulating evidence that toxic surface-covering molecules showed their cytotoxicity and biomolecules conjugated with QDs maintained their biological effects indicates that at least the biological properties of QDs are attributable to the QD-capping material rather than to the core metalloid complex itself. PMID- 17846715 TI - Stent graft treatment for thoracic and thoracoabdominal aortic disease using a unibody Z-stent that adapts to flexure. AB - Positioning a stent graft (SG) that adapts to the anatomical shape of the aorta is important to prevent complications after SG procedures to treat aortic disease. The Gianturco Z-stent has several benefits, but its rigid structure prevents adaptation to flexure. We improved this stent and studied its ability to adapt in the clinical environment. We positioned SGs and inspected their adaptability to flexure in an aortic arch model. We examined several gap lengths and strut directions, and determined the distance generated between the stent and the aortic wall. We found that adaptation was quite satisfactory with a gap of more than 10 mm or when the struts faced the major flexure or the side of the model aorta. Based on these findings and to facilitate placement, we manufactured the unibody Z-stent with 10-mm gaps. The unibody Z-stent was applied to treat thoracic and thoracoabdominal aortic disease in seven patients. The SG was positioned from the femoral or iliac artery in five patients and from an anastomosed graft to the ascending aorta after median sternotomy and bypass of the arch branches in two patients. A minor endoleak developed in one patient. None of the other six patients developed complications or died during the procedure, although one patient died in the hospital due to cerebral infarction. The unibody Z-stent was applied as a SG that adapts to flexure of the aorta and was easy to apply. The frequency of complications was apparently decreased after clinical application of the unibody Z-stent in SG treatment for thoracic and thoracoabdominal aortic disease. PMID- 17846716 TI - Development of in vivo tissue-engineered autologous tissue-covered stents (biocovered stents). AB - Biocovered stents, which are stents covered with autologous membranous tissues, were developed by applying a novel concept based on in vivo tissue engineering. Balloon-expandable stents crimped on silicone rods as a mold (diameter: 2 mm) were embedded into dorsal subcutaneous pouches in rabbits. After 1 month, the struts of the stents were fully encapsulated with membranous connective tissues formed around the silicone rods. Upon removing the silicone rod, stents covered with tubular connective tissues, in which the struts were completely impregnated, were obtained as biocovered stents. These tissues were composed mainly of collagen and fibroblasts and had a thickness of less than approximately 200 microm with an excellent high burst strength of approximately 1000 mmHg. The luminal surface of the tissues was extremely flat and smooth. The stents could be mounted on balloon catheters with a hand crimping tool and could be expanded by inflation with little damage to the tissues. It is anticipated that these novel stents may greatly enhance early normal vascular reconstruction with high reliability, thereby reducing the rate of in-stent restenosis. PMID- 17846718 TI - Estimation of mechanical heart valve cavitation in a pneumatic ventricular assist device. AB - In this study, we investigated the possibility of estimating the mechanical heart valve (MHV) cavitation intensity using the slope of the driving pressure (DP) just before valve closure in a pneumatic ventricular assist device. We installed a 23-mm Medtronic Hall valve at the inlet of our pneumatic ventricular assist device (VAD). Tests were conducted under physiologic pressures at heart rates ranging from 60 to 90 beats/min and cardiac outputs ranging from 4.5 to 6.7 l/min. The valve-closing velocity was measured with a CCD laster displacement sensor, and the images of MHV cavitation were recorded using a high-speed video camera. The cavitation cycle time (equal to the observed duration of the cavitation bubbles) was used as the MHV cavitation intensity. The valve-closing velocity increased as the heart rate increased. Most of the cavitation bubbles were observed near the valve stop, and the cavitation intensity increased as the heart rate increased. The slope of the DP at 20 ms before valve closure was used as an index of the cavitation intensity. There were differences in the slope of the DP between low and high heart rates, but the slope of the DP had a tendency to linearly increase with increasing valve-closing velocity. PMID- 17846717 TI - Neuraminidase produces a decrease of adherence of slime-forming Staphylococcus aureus to gelatin-impregnated polyester fiber graft fabric: an experimental study. AB - Because slime-forming microorganisms are the major causative agents of graft infections, we aimed to investigate bacterial adherence in slime-forming and nonslime-forming Staphylococcus aureus and to determine the role of neuraminidase (NANase) on adherence to gelatin-impregnated polyester fiber graft fabric. An in vitro model was developed to quantitatively measure bacterial adherence to the surface of the graft. The grafts were divided into two groups - those colonized with slime-forming S. aureus and those colonized with nonslime-forming S. aureus. The grafts were put into sterile tubes and human plasma was instilled and incubated at 37 degrees C to perform fibrin deposition on the grafts. After 48 h of incubation, grafts were drained and inoculated with slime-forming or nonslime forming S. aureus in triptic soy broth in the presence or absence of NANase. Following 36 h of incubation at 36 degrees C, grafts were vortexed and cultured to perform a colony count. Bacterial counts were expressed as total colony forming units per square centimeter of graft. Slime-forming S. aureus had greater affinity with the graft compared with nonslime-forming S. aureus (P < 0.05). The adherence of slime-forming S. aureus was impaired by NANase treatment (P < 0.001) but NANase treatment of nonslime-forming S. aureus did not change the adherence to the graft (P > 0.05). These results show that slime plays an important role in the pathogenesis of vascular graft infection. Adherence of slime-forming S. aureus can be decreased by NANase treatment. This may have implications for the development of neuraminidase-embedded vascular grafts to diminish biomaterial related infections. PMID- 17846719 TI - Effect of loxapine on electrical brain activity, intracranial pressure, and middle cerebral artery flow velocity in traumatic brain-injured patients. AB - INTRODUCTION: Delirium is a frequent complication of traumatic brain injury, especially during the weaning period. Antipsychotic drugs are often used in this case. Loxapine is a tricyclic antipsychotic drug with sedating properties. The effects of intravenous loxapine on EEG as well as on systemic and cerebral hemodynamics after traumatic brain injury are unknown. METHODS: Seven sedated and mechanically ventilated traumatic brain injured patients were studied 11 +/- 5 days after trauma. They were on continuous perfusion of sufentanil and midazolam. Left and right spectral edge frequency (SEFl, SEFr) of continuous EEG recording, intracranial pressure (ICP), mean flow velocity of the middle cerebral artery (MFV(MCA)) and mean arterial pressure (MAP) were simultaneously recorded and digitalized before and after loxapine infusion (10 mg in 10 min of continuous infusion). RESULTS: Loxapine induced no significant change on MAP, MFV. On the contrary, it decreased ICP and both SEFl, SEFr. ETCO(2 )and the dose of vasopressors were not altered during the study period. CONCLUSION: 10 mg of loxapine administered intravenously over 10 min decreased brain electrical activity. There is a concomitant reduction in ICP without any significant change in cerebral blood flow velocity. The use of intravenous loxapine to control agitation is not accompanied by deleterious hemodynamic or systemic effects in ICU's traumatic brain injured patients. PMID- 17846720 TI - Utilization of recombinant activated factor VII for intracranial hematoma evacuation in coagulopathic nonhemophilic neurosurgical patients with normal international normalized ratios. AB - BACKGROUND: Recombinant activated Factor VII (rFVIIa) has recently gained popularity for rapid reversal of coagulopathy during operative neurosurgery. Patients undergoing chronic subdural hematoma (CSDH) or epidural hematoma (EDH) evacuation often have their coagulation status judged by preoperative international normalized ratio (INR). We present our experience in two patients with significant clinical coagulopathy who were successfully reversed with rFVIIa in the setting of normal INR. METHODS: Patient one was a 79-year-old man with history of prostate cancer and three previous operative left CSDH evacuations, each complicated by coagulopathic bleeding, who presented with new-onset left EDH. Patient two was a 27-year-old woman with relapsed acute myelogenous leukemia with bilateral CSDH and mass effect on MRI. Neither patient had hemophilia, and preoperative INR was 1.2 in each case. Both patients underwent evacuation in the operating room, preceded by rFVIIa administration. RESULTS: Patient one underwent removal of his previous craniotomy flap followed by EDH evacuation. In patient two, coagulopathic bleeding upon surgical approach necessitated an additional dose of rFVIIa. Burrhole evacuation was well-tolerated with visible brain re expansion following irrigation. Each case occurred with minimal blood loss and relatively easy hemostasis, with postoperative CT and clinical course revealing adequate evacuation. Neither patient experienced thromboembolic complications or required re-operation. CONCLUSION: These two patients are the first to be examined for the use of rFVIIa for reversal of clinical coagulopathy in the setting of normal INR. Our experience suggests that normal INR should not be a deterrent for patients to receive rFVIIa in the setting of strong neurosurgical suspicion for underlying clinical coagulopathy. PMID- 17846721 TI - Neurological complications with acute sphenoid sinusitis a surgical emergency? AB - BACKGROUND: Isolated acute sphenoid sinusitis is an uncommon sinus infection, frequently misdiagnosed and not usually considered in the differential diagnosis of acute severe headache, with the potential of serious neurologic complications. OBJECTIVES: To describe two patients with acute sphenoid sinusitis who presented with acute onset of severe headache and consider the role of surgical management. DESIGN: Case report. SETTING: Tertiary care hospital. RESULTS: Patient 1 developed right cavernous sinus thrombosis and permanent visual loss in one eye, requiring sphenoidotomy following failure of medical treatment. Patient 2 experienced failure of the medical treatment. However, sphenoidotomy abated all his symptoms without any neurologic sequelae. CONCLUSION: It is important to be aware of acute sphenoid sinusitis in the setting of new onset severe headache, when imaging studies are unrevealing for intracranial pathology. Considering the serious consequences of failed medical treatment vis-a-vis the safety and efficacy of sphenoidotomy we propose surgical intervention at the time of diagnosis. PMID- 17846722 TI - Pseudo-subarachnoid hemorrhage in cerebellar infarction. AB - INTRODUCTION: The computed tomography (CT) appearance of subarachnoid hemorrhage (SAH) without subarachnoid blood has been labeled "pseudo-subarachnoid hemorrhage" (pseudo-SAH) and has been reported with several diffuse intracerebral insults including intrathecal contrast agents, meningitis, generalized cerebral edema, anoxic encephalopathy, and intracranial hypotension. METHODS: Single case report. RESULTS: We present a 43-year-old female who presented with vertigo and severe headache. Initial CT brain suggested SAH with hydrocephalus. Subsequent cerebral angiography was negative. Cerebrospinal fluid from an external ventricular drain (EVD) was negative for blood, and MRI brain revealed an acute stroke in the posterior inferior cerebellar artery (PICA) territory. CONCLUSION: Our case suggests that PICA infarction can be associated with the CT finding of pseudo-SAH, thereby mimicking the clinical and radiographic presentation of SAH. PMID- 17846723 TI - Metabolic engineering for pentose utilization in Saccharomyces cerevisiae. AB - The introduction of pentose utilization pathways in baker's yeast Saccharomyces cerevisiae is summarized together with metabolic engineering strategies to improve ethanolic pentose fermentation. Bacterial and fungal xylose and arabinose pathways have been expressed in S. cerevisiae but do not generally convey significant ethanolic fermentation traits to this yeast. A large number of rational metabolic engineering strategies directed among others toward sugar transport, initial pentose conversion, the pentose phosphate pathway, and the cellular redox metabolism have been exploited. The directed metabolic engineering approach has often been combined with random approaches including adaptation, mutagenesis, and hybridization. The knowledge gained about pentose fermentation in S. cerevisiae is primarily limited to genetically and physiologically well characterized laboratory strains. The translation of this knowledge to strains performing in an industrial context is discussed. PMID- 17846724 TI - Development of efficient xylose fermentation in Saccharomyces cerevisiae: xylose isomerase as a key component. AB - Metabolic engineering of Saccharomyces cerevisiae for ethanol production from D xylose, an abundant sugar in plant biomass hydrolysates, has been pursued vigorously for the past 15 years. Whereas wild-type S. cerevisiae cannot ferment D-xylose, the keto-isomer D-xylulose can be metabolised slowly. Conversion of D xylose into D-xylulose is therefore crucial in metabolic engineering of xylose fermentation by S. cerevisiae. Expression of heterologous xylose reductase and xylitol dehydrogenase does enable D-xylose utilisation, but intrinsic redox constraints of this pathway result in undesirable byproduct formation in the absence of oxygen. In contrast, expression of xylose isomerase (XI, EC 5.3.1.5), which directly interconverts D-xylose and D-xylulose, does not have these constraints. However, several problems with the functional expression of various bacterial and Archaeal XI genes have precluded successful use of XI in yeast metabolic engineering. This changed with the discovery of a fungal XI gene in Piromyces sp. E2, expression of which led to high XI activities in S. cerevisiae. When combined with over-expression of the genes of the non-oxidative pentose phosphate pathway of S. cerevisiae, the resulting strain grew anaerobically on D xylose with a doubling time of ca. 8 h, with the same ethanol yield as on glucose. Additional evolutionary engineering was used to improve the fermentation kinetics of mixed-substrate utilisation, resulting in efficient D-xylose utilisation in synthetic media. Although industrial pilot experiments have already demonstrated high ethanol yields from the D-xylose present in plant biomass hydrolysates, strain robustness, especially with respect to tolerance to inhibitors present in hydrolysates, can still be further improved. PMID- 17846725 TI - Consolidated bioprocessing for bioethanol production using Saccharomyces cerevisiae. AB - Consolidated bioprocessing (CBP) of lignocellulose to bioethanol refers to the combining of the four biological events required for this conversion process (production of saccharolytic enzymes, hydrolysis of the polysaccharides present in pretreated biomass, fermentation of hexose sugars, and fermentation of pentose sugars) in one reactor. CBP is gaining increasing recognition as a potential breakthrough for low-cost biomass processing. Although no natural microorganism exhibits all the features desired for CBP, a number of microorganisms, both bacteria and fungi, possess some of the desirable properties. This review focuses on progress made toward the development of baker's yeast (Saccharomyces cerevisiae) for CBP. The current status of saccharolytic enzyme (cellulases and hemicellulases) expression in S. cerevisiae to complement its natural fermentative ability is highlighted. Attention is also devoted to the challenges ahead to integrate all required enzymatic activities in an industrial S. cerevisiae strain(s) and the need for molecular and selection strategies pursuant to developing a yeast capable of CBP. PMID- 17846726 TI - Policy options to support biofuel production. AB - Biofuels for use in the transportation sector have been produced on a significant scale since the 1970s, using a variety of technologies. The biofuels widely available today are predominantly sugar- and starch-based bioethanol, and oilseed and waste oil-based biodiesel, although new technologies under development may allow the use of lignocellulosic feedstocks. Measures to promote the use of biofuels include renewable fuel mandates, tax incentives, and direct funding for capital projects or fleet upgrades. This paper provides a review of the policies behind the successful establishment of the biofuel industry in countries around the world. The impact of direct funding programs and excise tax exemptions are examined using the United States as a case study. It is found that the success of five major bioethanol producing states (Illinois, Iowa, Nebraska, South Dakota, and Minnesota) is closely related to the presence of funding designed to support the industry in its start-up phase, while tax exemptions on bioethanol use do not influence the development of production capacity. The study concludes that successful policy interventions can take many forms, but that success is equally dependent upon external factors, which include biomass availability, an active industry, and competitive energy prices. PMID- 17846727 TI - [Accidental intoxication with unlabeled, generic transdermal fentanyl patches caused by insufficient instruction]. AB - A somnolent 78-year-old male patient was brought to our emergency room by an ambulance with the presumptive diagnosis of stroke. Cranial computed tomography provided no evidence. On the intensive care unit of the neurosurgical department the patient was completely undressed. Covered by a sock and underwear the ICU staff found five unlabeled, transparent patches. Under the presumptive diagnosis of an opioid intoxication by a transdermal therapeutic system naloxone was infused over 3 days. The patient reported after rapidly awaking that fentanyl patches had been prescribed by his family practitioner the day before. The patient recovered without any sequelae. PMID- 17846728 TI - [Public service strike. Effects on operating room management and training at a surgical university clinic]. AB - BACKGROUND: In 2006 the longest strike so far in the German health service occurred. Contrary to most hospitals in public authorities, the medical doctors of the University Hospital of Homburg/Saar did not participate in the strike, leading to pronounced tensions between patients, strikers and medical staff. MATERIAL AND METHODS: The effect of the strike on operating room (OR) management, medical personnel resource planning, and surgical training were compared with the remaining period of the year 2006. RESULTS: Elective surgical procedures were accomplished significantly more frequently by more qualified surgeons, leading to shorter OR time; surgical training was performed significantly less. The rate of emergency operations and the care of tumor patients increased significantly during the strike. CONCLUSION: Surgical training was neglected during the strike. Transferring non-job-related tasks to medical doctors and expanding their working time allowed optimal utilization of the limited resources. PMID- 17846729 TI - [Febrile ulceronecrotic Mucha-Habermann syndrome]. PMID- 17846730 TI - [Sucessful therapy of nodular amyloidosis with CO2 laser]. PMID- 17846731 TI - [The German Network for Systemic Scleroderma]. AB - Systemic scleroderma (SSc) is a rare, heterogenous, multisystem disease affecting different organ systems and therefore requires interdisciplinary management and patient care. The German Network for Systemic Scleroderma, funded by the country's Federal Ministry of Education and Research, was established 3 years ago and comprises dermatologists, rheumatologists, pulmonologists, and nephrologists from more than 40 medical centers. The registry contains data of more than 1800 patients. Analysis of the continually growing body of data will form the basis for the development of standardized recommendations for diagnosis and treatment of SSc. PMID- 17846732 TI - [Influence of diabetes incidence by ramipril and rosiglitazone: DREAM study (diabetes reduction assessment with ramipril and rosiglitazone medication)]. PMID- 17846733 TI - Connective tissue growth factor: a crucial cytokine-mediating cardiac fibrosis in ongoing enterovirus myocarditis. AB - Dilated cardiomyopathy (DCM) as a consequence of viral myocarditis is a worldwide cause of morbidity and death. The deposition of matrix proteins, such as collagen, in the course of ongoing viral myocarditis results in cardiac remodeling and finally in cardiac fibrosis, the hallmark of DCM. To identify mediators of virus-induced cardiac fibrosis, microarray analysis was conducted in a murine model of chronic coxsackievirus B3 (CVB3) myocarditis. By this attempt, we identified connective tissue growth factor (CTGF) as a novel factor highly expressed in infected hearts. Further investigations by quantitative reverse transcription polymerase chain reaction and Western blot analysis confirmed a strong induction of cardiac CTGF expression in the course of CVB3 myocarditis. By in situ hybridization and immunohistochemistry, basal CTGF messenger ribonucleic acid (mRNA) and protein expression were confined in noninfected control hearts mainly to endothelial cells, whereas in CVB3-infected hearts, also numerous fibroblasts were found to express CTGF. Regulation of CTGF is known to be basically mediated by transforming growth factor (TGF)-beta. In the course of CVB3 myocarditis, CTGF upregulation coincided with increased cardiac TGF-beta and procollagen type I mRNA expression, preceding the formation of fibrotic lesions. In in vitro experiments, we found that downregulation of CVB3 replication by means of small interfering RNAs (siRNAs) reverses the upregulation of CTGF mRNA expression. In contrast, downregulation of CTGF by siRNA molecules did not significantly reduce viral load, indicating that CTGF is not essential for CVB3 life cycle. The significantly enhanced transcript levels of TGF-beta, CTGF, and procollagen type I in cultivated CVB3-infected primary cardiac fibroblasts substantiate the role of fibroblasts as a relevant cell population in cardiac remodeling processes. We conclude that CTGF is a crucial molecule in the development of fibrosis in ongoing enteroviral myocarditis. Thus, downregulation of cardiac CTGF expression may open novel therapeutic approaches counteracting the development of cardiac fibrosis and subsequent heart muscle dysfunction. PMID- 17846734 TI - [Current aspects of secondary prevention of ischemic stroke]. AB - Secondary prevention including lifestyle modulation and medical interventions remain the basic principle in our therapeutic challenge to reduce the risk of recurrent subsequent ischemic stroke. The substantial number of randomized clinical trials published in the past 2 years was broadened our evidence-based therapeutic armament in the field of secondary prevention of ischemic stroke. An update of current knowledge in secondary stroke prevention is presented in this review on the basis of the 2007 revised guidelines of the German Neurological Society and the German Stroke Society. Special emphasis is given to medical and nonmedical modulation of cardiovascular risk factors (treatment of hypertension, hypercholesterolemia, and diabetes mellitus), prophylactic vitamin supplementation, and the use of platelet inhibitors and treatment of symptomatic intracranial stenosis. PMID- 17846735 TI - [Functional magnetic resonance imaging before motor cortex stimulation for phantom limb pain]. AB - This study deals with the diagnostic value of functional magnetic resonance imaging (fMRI) in a patient with phantom limb pain following traumatic amputation of the right arm. After failure with medication, resection of stump neurinoma, and spinal cord stimulation, fMRI with evidence of cortical reorganization was performed. Tactile stimulation of the perioral region and motor imagery with cranial, tactile stimulation of the stump led to a caudal shift in fMRI activity. Subsequent motor cortex stimulation brought relief from the pain. By detecting cortical reorganization, fMRI contributes to the indication for motor cortex stimulation for phantom pain and aids in electrode positioning. PMID- 17846736 TI - [Psychopathology and treatment of borderline personality disorder]. AB - Borderline personality disorder (BPD) is a severe psychiatric disorder accounting for about 30% of the total cost for psychiatric inpatient care in the Federal Republic of Germany. Suicidality, self-harm, and severe deterioration of self esteem lead to chronic suffering for patients and the social environment. With a prevalence rate of 1.5%, BPD is more frequent than schizophrenic disorders. Within the last years, empirically based knowledge concerning the psychopathology, etiopathogenesis, and treatment of BPD have significantly improved. Today most researchers postulate pervasive affective dysregulation at the core of borderline symptomatology and see it as the consequence of an interplay between genetic vulnerability, sociobiographic experience, and dysfunctional behavior. Disorder-specific psychotherapeutic treatments, especially dialectical behavior therapy, show significant improvements in both in and outpatient settings. Studies on psychopharmacological treatment with promising results have also recently been published. Sufficient outpatient treatment by trained psychotherapists is underdeveloped. Hence, specialized inpatient centers assume this task. PMID- 17846737 TI - [Privatization in psychiatry and psychotherapy - between shareholder value and health care governed by law]. PMID- 17846739 TI - [Neoadjuvant and adjuvant chemotherapy in patients with advanced penile cancer]. AB - With an incidence of 0.1-0.9/100,000 men per year penile cancer is a rare cancer of the urogenital tract in Western Europe. At the time of initial diagnosis up to 45% of the patients already demonstrate metastatic disease and need some type of systemic treatment. It is the aim of this paper to review the current concepts of adjuvant and neoadjuvant chemotherapy for locally advanced penile cancer. A curative effect of combined surgical and cytotoxic management can only be achieved in patients with locoregional spread to the lymph nodes, but not with systemic spread. Although there are prospective randomized trials available indicating the optimal cytotoxic regime, cisplatin-based protocols or combination therapies with bleomycin, vincristine, and methotrexate appear to be the most effective options. Finally, there are no data available with regard to the effect of adjuvant chemotherapy on progression-free survival. In patients with locoregional bulky disease or with fixed inguinal lymph nodes, neoadjuvant chemotherapy will result in a partial response in 20-60% of patients and enables complete resection of the mass. For the future, the use of taxane-based chemotherapy as described for squamous cell cancer of other origin might improve outcome. PMID- 17846740 TI - [DiaPat test for prostate cancer diagnosis]. PMID- 17846741 TI - Comparison of gene expression between upland and lowland rice cultivars under water stress using cDNA microarray. AB - To elucidate the differences in the regulation of water stress tolerance between two genotypes of rice, upland-rice (UR, resistant to water stress) and lowland rice (LR, susceptible to water stress), we constructed subtracted cDNA libraries from polyethyleneglycol (PEG)-treated and non-treated rice seedlings (IRAT109, an upland-rice variety) by suppression subtractive hybridization (SSH), from which about 2,000 recombinant colonies were picked and amplified. Then, a cDNA microarray containing these expressed sequence tags (ESTs) was used to analyze the gene expression profiles in UR and LR in response to PEG treatment. Microarray data revealed that the majority of genes expressed in UR and LR are almost identical and Student's t test showed that 13% of all the ESTs detected in leaves and 7% of that in roots expressed differentially in transcripts abundance between the two genotypes. After sequencing, it was found that 64 and 79 unique ESTs expressed at higher levels in UR and LR, respectively. Many of the ESTs that showed higher expression in UR upon PEG treatment represented genes for transcription factors, genes playing roles in detoxification or protection against oxidative stress, and genes that help in maintaining cell turgor. In contrast, some ESTs that showed higher expression in LR were genes functioning in the degradation of cellular components. Based on data from this study and previous reports, we suggest that overexpression of some genes that expressed at higher level in UR may improve water stress tolerance in LR and other plant species. PMID- 17846742 TI - Development of SRAP, SNP and multiplexed SCAR molecular markers for the major seed coat color gene in Brassica rapa L. AB - Seed coat color inheritance in B. rapa was studied in F(1), F(2), F(3), and BC(1) progenies from a cross of a Canadian brown-seeded variety 'SPAN' and a Bangladeshi yellow sarson variety 'BARI-6'. A pollen effect was found when the yellow sarson line was used as the maternal parent. Seed coat color segregated into brown, yellow-brown and bright yellow classes. Segregation was under digenic control where the brown or yellow-brown color was dominant over bright yellow seed coat color. A sequence related amplified polymorphism (SRAP) marker linked closely to a major seed coat color gene (Br1/br1) was developed. This dominant SRAP molecular marker was successfully converted into single nucleotide polymorphism (SNP) markers and sequence characterized amplification region (SCAR) markers after the extended flanking sequence of the SRAP was obtained with chromosome walking. In total, 24 SNPs were identified with more than 2-kb sequence. A 12-bp deletion allowed the development of a SCAR marker linked closely to the Br1 gene. Using the five-fluorescence dye set supplied by ABI, four labeled M13 primers were integrated with different SCAR primers to increase the throughput of SCAR marker detection. Using multiplexed SCAR markers targeting insertions and deletions in a genome shows great potential for marker assisted selection in plant breeding. PMID- 17846743 TI - Vibrotactile threshold measurement for detecting peripheral neuropathy: defining variability and a normal range for clinical and research use. AB - AIMS/HYPOTHESIS: We aimed to define normal ranges for vibration sense as measured by vibratory perception thresholds (VPTs) using biothesiometry. METHODS: We performed biothesiometry in a community-dwelling sample of 901 people aged 55 to 85 years who did not have diabetes. We quantitated the variation between repeat measures using analysis of variance and Bland-Altman plots. We also plotted the age- and sex-specific reference ranges. RESULTS: We found small but statistically significant differences between repeat measures using the ascending and descending method of limits. Statistically higher vibration thresholds were noted on the right arm and leg compared with the left. Significantly higher vibration thresholds were also seen in men vs women for both lower limbs. We also defined sex-specific reference intervals (normal ranges) for biothesiometry for older persons and quantitated the increase in vibration threshold with increasing age. CONCLUSIONS/INTERPRETATION: For reliability, it may be sufficient to obtain the average of two ascending measures separated by at least 1 min in just the right hand or right foot, since this is usually the one with the higher threshold. Although identical reference ranges can be used for men and women for the upper limb, there are significant differences in the lower limbs. The major determinant of VPT is age: we have established age-specific norms for VPT testing for adults between 55 and 85 years of age. PMID- 17846744 TI - HDL particles from type 1 diabetic patients are unable to reverse the inhibitory effect of oxidised LDL on endothelium-dependent vasorelaxation. AB - AIMS/HYPOTHESIS: In healthy individuals, HDL can counteract the inhibition of vasorelaxation induced by oxidised LDL. Several abnormalities such as increased size, glycation and decreased paraoxonase activity have been reported for HDL from type 1 diabetic patients. Thus, we hypothesised that the ability of HDL to protect vessels against impairments of vasorelaxation would be decreased in these patients. METHODS: We compared the ability of HDL from 18 type 1 diabetic patients and 12 control participants to counteract the inhibition of endothelium dependent relaxation induced by oxidised LDL on rabbit aorta rings. RESULTS: Serum triacylglycerol and total cholesterol, LDL- and HDL-cholesterol were similar in type 1 diabetic and control participants. Fasting glycaemia and the HDL-fructosamine level were higher in diabetic patients than in controls (9.06 +/ 3.55 vs 5.27 +/- 0.23 mmol/l, p < 0.005; and 10.2 +/- 3.2 vs 7.7 +/- 2.5 micromol/g protein, p < 0.05, respectively). HDL composition, size and paraoxonase activity were similar in both groups. HDL from controls reduced the inhibitory effect of oxidised LDL on maximal relaxation (E (max); 79.3 +/- 11.8 vs 66.4 +/- 11.7%, p < 0.05), whereas HDL from type 1 diabetic patients had no effect (E (max) = 70.6 +/- 17.4 vs 63.9 +/- 17.2%, NS). In type 1 diabetic patients, E (max) was not correlated with glycaemia or the HDL-fructosamine level. CONCLUSIONS/INTERPRETATION: HDL particles from type 1 diabetic patients do not protect against inhibition of endothelium-dependent vasorelaxation induced by oxidised LDL, in contrast to HDL particles from healthy individuals. This defect cannot be explained by abnormalities in HDL composition, size or paraoxonase activity, and may contribute to the early development of atherosclerotic lesions in type 1 diabetic patients. PMID- 17846745 TI - Association of fasting glucagon and proinsulin concentrations with insulin resistance. AB - AIMS/HYPOTHESIS: Hyperproinsulinaemia and relative hyperglucagonaemia are features of type 2 diabetes. We hypothesised that raised fasting glucagon and proinsulin concentrations may be associated with insulin resistance (IR) in non diabetic individuals. METHODS: We measured IR [by a euglycaemic-hyperinsulinaemic (240 pmol min(-1) m(-2)) clamp technique] in 1,296 non-diabetic (on a 75 g OGTT) individuals [716 women and 579 men, mean age 44 years, BMI 26 kg/m(2) (range 18 44 kg/m(2))] recruited at 19 centres in 14 European countries. IR was related to fasting proinsulin or pancreatic glucagon concentrations in univariate and multivariate analyses. Given its known relationship to IR, serum adiponectin was used as a positive control. RESULTS: In either sex, both glucagon and proinsulin were directly related to IR, while adiponectin was negatively associated with it (all p < 0.0001). In multivariate models, controlling for known determinants of insulin sensitivity (i.e. sex, age, BMI and glucose tolerance) as well as factors potentially affecting glucagon and proinsulin (i.e. fasting plasma glucose and C peptide concentrations), glucagon and proinsulin were still positively associated, and adiponectin was negatively associated, with IR. Finally, when these associations were tested as the probability that individuals in the top IR quartile would have hormone levels in the top quartile of their distribution independently of covariates, the odds ratio was approximately 2 for both glucagon (p = 0.05) and proinsulin (p = 0.02) and 0.36 for adiponectin (p < 0.0001). CONCLUSIONS/INTERPRETATION: Whole-body IR is independently associated with raised fasting plasma glucagon and proinsulin concentrations, possibly as a result of IR at the level of alpha cells and beta cells in pancreatic islets. PMID- 17846746 TI - Prediction of mortality rate in type 2 diabetes: estimated glomerular filtration rate underestimates the true rate. PMID- 17846747 TI - Automatic selection of breathing pattern using adaptive support ventilation. AB - OBJECTIVE: In a cohort of mechanically ventilated patients to compare the automatic tidal volume (VT)-respiratory rate (RR) combination generated by adaptive support ventilation (ASV) for various lung conditions. DESIGN AND SETTING: Prospective observational cohort study in the 11-bed medicosurgical ICU of a general hospital. PATIENTS: 243 patients receiving 1327 days of invasive ventilation on ASV. MEASUREMENTS: Daily collection of ventilator settings, breathing pattern, arterial blood gases, and underlying clinical respiratory conditions categorized as: normal lungs, ALI/ARDS, COPD, chest wall stiffness, or acute respiratory failure. RESULTS: Overall the respiratory mechanics differed significantly with the underlying conditions. In passive patients ASV delivered different VT-RR combinations based on the underlying condition, providing higher VT and lower RR in COPD than in ALI/ARDS: 9.3ml/kg (8.2-10.8) predicted body weight (PBW) and 13 breaths/min (11-16) vs. 7.6ml/kg (6.7-8.8) PBW and 18 breaths/min (16-22). In patients actively triggering the ventilator the VT-RR combinations did not differ between COPD, ALI/ARDS, and normal lungs. CONCLUSIONS: ASV selects different VT-RR combinations based on respiratory mechanics in passive, mechanically ventilated patients. PMID- 17846748 TI - Monitoring brain tissue oxygen tension in brain-injured patients reveals hypoxic episodes in normal-appearing and in peri-focal tissue. AB - OBJECTIVE: We compared brain tissue oxygen tension (PtiO2) measured in peri-focal and in normal-appearing brain parenchyma on computerized tomography (CT) in patients following traumatic brain injury (TBI). DESIGN: Prospective observational study. SETTING: Neurointensive care unit. PATIENTS AND PARTICIPANTS: Thirty-two consecutive TBI patients were subjected to PtiO2 monitoring. INTERVENTIONS: Peri-focal tissue was identified by the presence of a hypodense area of the contusion and/or within 1 cm from the core of the contusion. The position of the tip of the PtiO2 probe was assessed at follow-up CT scan. MEASUREMENTS AND RESULTS: Mean PtiO2 in the peri-contusional tissue was 19.7+/-2.1 mmHg and was lower than PtiO2 in normal-appearing tissue (25.5+/-1.5 mmHg, p < 0.05), despite a greater cerebral perfusion pressure (CPP) (73.7+/-2.3 mmHg vs. 67.4+/-1.4 mmHg, p < 0.05). We observed both in peri-focal tissue and in normal-appearing tissue episodes of brain hypoxia (PtiO2 < 20 mmHg for at least 10 min), whose median duration was longer in peri-focal tissue than in normal appearing tissue (51% vs. 34% of monitoring time, p < 0.01). In peri-focal tissue, we observed a progressive PtiO2 increase from pathologic to normal values (p < 0.01). CONCLUSIONS: Multiple episodes of brain hypoxia occurred over the first 5 days following severe TBI. PtiO2 was lower in peri-contusional tissue than in normal-appearing tissue. In peri-contusional tissue, a progressive increase of PtiO2 from pathologic to normal values was observed over time, suggestive of an improvement at microcirculatory level. PMID- 17846749 TI - High level of soluble expression in Escherichia coli and characterisation of the CyaA pore-forming fragment from a Bordetella pertussis Thai clinical isolate. AB - Bordetella pertussis adenylate cyclase toxin-haemolysin (CyaA) can permeabilise erythrocytes by forming lytic pores. Here, a gene segment encoding CyaA pore forming (CyaA-PF) domain cloned from genomic DNA of B. pertussis Thai isolate was over-expressed in Escherichia coli as a 126-kDa soluble protein which cross reacted with anti-RTX monoclonal antibody. By co-expressing with acyltransferase CyaC, the CyaA-PF protein was found palmitoylated at Lys(983). Unlike E. coli lysate with the non-acylated form, the lysate containing acylated CyaA-PF exhibited high haemolytic activity against sheep erythrocytes. This study presents that the recombinant CyaA-PF protein comprising pore-forming domain can be expressed separately as soluble native-folded precursor that conserves at least part of its functionality. PMID- 17846750 TI - Expression of putative virulence factors in the potato pathogen Clavibacter michiganensis subsp. sepedonicus during infection. AB - The Gram-positive bacterium Clavibacter michiganensis subsp. sepedonicus is the causal agent of bacterial wilt and ring rot of potato. So far, only two proteins have been shown to be essential for virulence, namely a plasmid-encoded cellulase CelA and a hypersensitive response-inducing protein. We have examined the relative expression of CelA and eight putative virulence factors during infection of potato and in liquid culture, using quantitative real-time PCR. The examined putative virulence genes were celB, a cellulase-encoding gene and genes encoding a pectate lyase, a xylanase and five homologues of the Clavibacter michiganensis subsp. michiganensis pathogenicity factor Pat-1 thought to encode a serine protease. Six of the nine assayed genes were up-regulated during infection of potato, including celA, celB, the xylanase gene, and two of the pat genes. The pectate lyase gene showed only slightly elevated expression, whereas three of the five examined pat genes were down-regulated during infection in potato. Interestingly, the two up-regulated pat genes showed a noticeable sequence difference compared to the three down-regulated pat genes. These results reveal several new proteins that are likely to be involved in Clavibacter michiganensis subsp. sepedonicus pathogenicity. PMID- 17846752 TI - Integrated sorption-energy-dispersive X-ray fluorescence detection for automatic determination of lead and cadmium in low-concentration solutions. AB - Sorbent material packed in a PTFE laboratory-made flow cell located in the specimen holder of an energy-dispersive X-ray fluorescence (EDXRF) detector has been used for in situ solid-phase extraction (SPE) preconcentration-detection of metals. The flow cell was connected to a single-channel flow-injection (FI) manifold (for full automation of the steps and proper development of the method) by two PTFE tubes of 0.5-mm inner diameter introduced into the spectrometer specimen holder by a small orifice without distortion or modification of the instrument. The optical window open in the PTFE flow cell was adjusted to the X ray irradiation zone of the spectrometer and fixed to it. The approach was tested by using both Pb and Cd aqueous solutions and a Dowex 50 cation-exchange resin as a sorbent, and flushing the sample through the flow cell for EDXRF measurements after removal of the sample matrix. The limits of detection and the limits of quantification (LOQs) thus obtained were 0.15 and 0.5 microg for Pb and 0.3 and 0.8 microg for Cd, respectively, values that allow the approach to be used for the analysis of drinking water by injecting a 100-mL sample into the FI manifold, taking into account the EC drinking water directives. The linear dynamic ranges are between the LOQ and 600 microg for both analytes. The method was validated by the standard addition method using tap-water samples. In addition, the integrated SPE-EDXRF approach enables the study of the variables influencing the sorption step-namely the effects of the volume of sample flushed through the column, concentrations of the analytes in the sample, breakthrough volume of the resin, elution profiles, sample pH and retention and elution flow rates-in an automatic, cheap, fast and precise way. PMID- 17846751 TI - In vitro translation with [34S]-labeled methionine, selenomethionine, and telluromethionine. AB - Heteroisotope and heteroatom tagging with [(34)S]-enriched methionine (Met), selenomethionine (SeMet), and telluromethionine (TeMet) was applied to in vitro translation. Green fluorescent protein (GFP) and JNK stimulatory phosphatase-1 (JSP-1) genes were translated with wheat germ extract (WGE) in the presence of Met derivatives. GFPs containing Met derivatives were subjected to HPLC coupled with treble detection, i.e., a photodiode array detector, a fluorescence detector, and an inductively coupled plasma mass spectrometer (ICP-MS). The activities of JSP-1-containing Met derivatives were also measured. GFP and JSP-1 containing [(34)S]-Met and SeMet showed comparable fluorescence intensities and enzyme activities to those containing naturally occurring Met. TeMet was unstable and decomposed in WGE, whereas SeMet was stable throughout the experimental period. Thus, although Te was the most sensitive to ICP-MS detection among S, Se, and Te, TeMet was less incorporated into the proteins than Met and SeMet. Finally, the potential of heteroisotope and heteroatom tagging of desired proteins in in vitro translation followed by ICP-MS detection was discussed. [figure: see text] TeMet was less incorporated into GFP than Met and SeMet due to its instability in WGE. PMID- 17846753 TI - Characterization of nanoindentation-induced residual stresses in human enamel by Raman microspectroscopy. AB - The objective of this research was to investigate nanoindentation-induced residual stresses in human enamel using Raman microspectroscopy and establish if this approach can be used as a stress meter. Healthy human premolars and sintered hydroxyapatite samples were embedded, cut, and the surfaces were polished finely with a 0.05 microm polishing paste before Berkovich and spherical indentations were made with a force of 100 mN. Spectra were collected using a Renishaw Raman InVia reflex microscope equipped with an air-cooled charge-coupled device (CCD) camera. Sample excitation was achieved using either an argon ion laser emitting at 514.5-nm or a NIR diode laser emitting at 830-nm. The residual micro stresses within and surrounding the indentation impressions were monitored by mapping the position of the nu(1)(PO(4)) band of (crystalline) hydroxyapatite. The Raman maps coincided well with the optical micrographs of the samples. Despite the presence of a fluorescence background from the organic component of human enamel, spectra collected using 514.5-nm excitation exhibited more significant shifts in the position of the nu(1)(PO(4)) band than spectra collected using 830-nm excitation. This implies that the former excitation may be a more appropriate excitation for stress detection. It was concluded that Raman microspectroscopy provides a novel high-resolution and non-destructive method for exploring the role of microstructure on the residual stress distribution within natural biocomposites. PMID- 17846754 TI - Properties of attentional selection during the preparation of sequential saccades. AB - We examined the allocation of attention during the preparation of sequences of saccades in a dual task paradigm. As a primary task, participants performed a sequence of two or three saccades to targets arranged on a circular array. The secondary task was a two-alternative discrimination in which a critical discrimination stimulus (digital "E" or "3") was presented among distractors either at one of the saccade goals or at any other position. The findings show that discrimination performance is enhanced at all the saccade target locations of the planned sequence, while it is close to chance level at the positions that are not relevant for the saccade sequence. An analysis of the discrimination performance at the intermediate locations indicates that saccade target selection involves spatially distinct, non-contiguous foci of attention. Further, our findings demonstrate that the movement-relevant locations are selected in parallel rather than serially in time. We conclude that during the preparation of a saccade sequence--well before the actual execution of the eye movement- attention is allocated in parallel to each of the individual movement targets. PMID- 17846755 TI - Age-dependent dynamic sonographic measurement of pediatric clubfoot. AB - BACKGROUND: US shows promise in evaluating clubfeet. In order to assess responses to therapy, the measurements of normal feet and clubfeet must be known. OBJECTIVE: To investigate the role of US measurement in quantitatively evaluating normal feet and clubfeet in children, and to assess changes in these feet with age. MATERIALS AND METHODS: Patients <1 year old with unilateral or bilateral clubfoot deformity underwent US examination of the foot with specific attention to the medial malleolar to navicular (MMN) distance. Measurements were made in neutral and full adduction positions, and in the abduction position simulating the Ponseti maneuver. Children undergoing US for other reasons had the same imaging performed and served as controls. RESULTS: A total of 127 feet in 66 children were evaluated (20 children had bilateral clubfeet, 25 had unilateral clubfoot, and 21 had normal feet). Clubfeet had significantly (P < 0.001) lower MMN measurements at all three positions than control feet. These distances increased with patient age for both normal feet and clubfeet, but the rate of increase was less for clubfeet. CONCLUSION: Normal feet and clubfeet exhibit marked differences in MMN distances, as well as differences in rate of change over time. By understanding the age-dependent variability of normal feet and clubfeet, dynamic sonography can help assess clubfoot anatomy and could help to assess the effect of treatment interventions. PMID- 17846756 TI - Focused dynamic sonographic examination of the congenital clubfoot. AB - BACKGROUND: US readily demonstrates cartilaginous structures, and static sonography has shown potential in evaluating clubfoot deformity. OBJECTIVE: To investigate the potential of dynamic sonography in the evaluation of the congenital clubfoot. MATERIALS AND METHODS: Sonography was used for static and dynamic stress evaluation of 13 clubfeet and 35 normal feet in 24 patients (ages 0-32 weeks). Dynamic foot sonography was performed using a single-operator bimanual scanning technique. The examination involved coronal oblique evaluation of the medial malleolar-navicular (MMN) distance and the calcaneocuboid relationship, sagittal evaluation of the talonavicular relationship, and transverse evaluation of navicular subluxation, rotation, and deformation. Dynamic abduction/adduction stress maneuvers were performed, measured by the MMN. RESULTS: The clubfoot "gristle" is a consistent, measurable soft-tissue landmark in clubfeet, connecting the medial malleolus to the medial navicular and talus. Mean MMN distances in clubfeet in the neutral position and abduction were significantly different from these distances in the normal paired foot (differences of 8.7 mm neutral position and 7.94 mm abduction), as compared to bilateral normal feet (differences of 0.98 mm neutral position and 1.43 mm abduction). Navicular subluxation showed good correlation between highly deformed and subluxated navicular bones and a tight medial clubfoot complex. CONCLUSIONS: Focused dynamic foot sonography is useful in providing a specific and detailed functional preoperative and/or postoperative assessment of the congenital clubfoot. PMID- 17846757 TI - A spectrum of neuroradiological findings in children with haemophagocytic lymphohistiocytosis. AB - BACKGROUND: Haemophagocytic lymphohistiocytosis (HLH) is a rare multisystem disorder. CNS involvement is a frequent and poor prognostic component. Better neuroradiological surveillance may be beneficial for patient management and outcome. OBJECTIVE: To describe various neuroradiological findings in nine patients with HLH with an emphasis on correlation with disease activity and treatment response. MATERIALS AND METHODS: Between 1996 and 2007, nine children with HLH with CNS involvement were identified in a single centre. Neuroradiological findings from CT, MRI, and proton MR spectroscopy, and the clinical records of the nine children were retrospectively reviewed. The frequency, distribution, characteristics of abnormal neuroradiological findings and changes during follow-up were correlated with clinical findings. RESULTS: Initial abnormal findings included multiple nodular or ring-enhancing parenchymal lesions, a laminated pattern of nodular parenchymal lesions on T2-weighted images, leptomeningeal enhancement, confluent parenchymal lesions, mild ventriculomegaly, and diffuse brain oedema. On follow-up imaging studies, haemorrhagic transformation and atrophy were seen where brain parenchymal lesions had been previously. These abnormal neuroradiological findings showed good correlation with clinical findings. Proton MR spectroscopy also demonstrated typical changes of metabolites during the course of the disease. CONCLUSION: A spectrum of neuroradiological findings in children with HLH is well matched with the clinical course of the disease and, therefore, a comprehensive analysis of the findings is useful to monitor disease activity and treatment responses. PMID- 17846760 TI - Biofilms of As(III)-oxidising bacteria: formation and activity studies for bioremediation process development. AB - The formation and activity of an As(III)-oxidising biofilm in a bioreactor, using pozzolana as bacterial growth support, was studied for the purpose of optimising fixed-bed bioreactors for bioremediation. After 60 days of continuous functioning with an As(III)-contaminated effluent, the active biofilm was found to be located mainly near the inflow rather than homogeneously distributed. Biofilm development by the CAsO1 bacterial consortium and by Thiomonas arsenivorans was then studied both on polystyrene microplates and on pozzolana. Extra-cellular polymeric substances (EPS) and yeast extract were found to enhance bacteria attachment, and yeast extract also appears to increase the kinetics of biofilm formation. Analysis of proteins, sugars, lipids and uronic acids indicate that sugars were the main EPS components. The specific As(III)-oxidase activity of T. arsenivorans was higher (by ninefold) for planktonic cells than for sessile ones and was induced by As(III). All the results suggest that the biofilm structure is a physical barrier decreasing As(III) access to sessile cells and thus to As(III) oxidase activity induction. The efficiency of fixed-bed reactors for the bioremediation of arsenic-contaminated waters can be thus optimised by controlling different factors such as temperature and EPS addition and/or synthesis to increase biofilm density and activity. PMID- 17846761 TI - Application of Plackett-Burman experimental design and Doehlert design to evaluate nutritional requirements for xylanase production by Alternaria mali ND 16. AB - The objective of this study was to use statistically based experimental designs for the optimization of xylanase production from Alternaria mali ND-16. Ten components in the medium were screened for nutritional requirements. Three nutritional components, including NH(4)Cl, urea, and MgSO(4), were identified to significantly affect the xylanase production by using the Plackett-Burman experimental design. These three major components were subsequently optimized using the Doehlert experimental design. By using response surface methodology and canonical analysis, the optimal concentrations for xylanase production were: NH(4)Cl 11.34 g L(-1), urea 1.26 g L(-1), and MgSO(4) 0.98 g L(-1). Under these optimal conditions, the xylanase activity from A. mali ND-16 reached 30.35 U mL( 1). Verification of the optimization showed that xylanase production of 31.26 U mL(-1) was achieved. PMID- 17846762 TI - Control of chemoselectivity of microbial reaction with resin adsorbent: enhancement of Baeyer-Villiger oxidation over reduction. AB - Amberlite XAD-7, a hydrophobic polymer, was used to change microbial reaction of ketones from reduction to Baeyer-Villiger (BV) oxidation. Thus, D. magnusii NBRC 4600 and G. reessii NBRC 1112 could catalyze the BV reaction of ketones in the presence of the polymer while reduction of the substrates proceeded, and BV oxidation was scarcely found in the absence of the polymer. PMID- 17846763 TI - Assimilable nitrogen utilisation and production of volatile and non-volatile compounds in chemically defined medium by Saccharomyces cerevisiae wine yeasts. AB - Surveys conducted worldwide have shown that a significant proportion of grape musts are suboptimal for yeast nutrients, especially assimilable nitrogen. Nitrogen deficiencies are linked to slow and stuck fermentations and sulphidic off-flavour formation. Nitrogen supplementation of grape musts has become common practice; however, almost no information is available on the effects of nitrogen supplementation on wine flavour. In this study, the effect of ammonium supplementation of a synthetic medium over a wide range of nitrogen values on the production of volatile and non-volatile compounds by two high-nitrogen-demand wine fermentation strains of Saccharomyces cerevisiae was determined. To facilitate this investigation, a simplified chemically defined medium that resembles the nutrient composition of grape juice was used. Analysis of variance revealed that ammonium supplementation had significant effects on the concentration of residual sugar, L-malic acid, acetic acid and glycerol but not the ethanol concentration. While choice of yeast strain significantly affected half of the aroma compounds measured, nitrogen concentrations affected 23 compounds, including medium-chain alcohols and fatty acids and their esters. Principal component analysis showed that branched-chain fatty acids and their esters were associated with low nitrogen concentrations, whereas medium-chain fatty esters and acetic acid were associated with high nitrogen concentrations. PMID- 17846764 TI - Azoreductase from Rhodobacter sphaeroides AS1.1737 is a flavodoxin that also functions as nitroreductase and flavin mononucleotide reductase. AB - Previously reported azoreductase (AZR) from Rhodobacter sphaeroides AS1.1737 was shown to be a flavodoxin possessing nitroreductase and flavin mononucleotide (FMN) reductase activities. The structure model of AZR constructed with SWISS MODEL displayed a flavodoxin-like fold with a three-layer alpha/beta/alpha structure. With nitrofurazone as substrate, the optimal pH value and temperature were 7.0 and 50 degrees C, respectively. AZR could reduce a number of nitroaromatic compounds including 2,4-dinitrotoluene, 2,6-dinitrotoluene, 3,5 dinitroaniline, and 2,4,6-trinitrotoluene (TNT). TNT resulted to be the most efficient nitro substrate and was reduced to hydroxylamino-dinitrotoluene. Both NADH and NADPH could serve as electron donors of AZR, where the latter was preferred. Externally added FMN was also reduced by AZR via ping-pong mechanism and was a competitive inhibitor of NADPH, methyl red, and nitrofurazone. AZR with broad substrate specificity is a member of a new nitro/FMN reductase family demonstrating potential application in bioremediation. PMID- 17846767 TI - Yttrium 90 Bremsstrahlung SPECT/CT scan demonstrating areas of tracer/tumour uptake. PMID- 17846766 TI - Peripheral metabolism of (R)-[11C]verapamil in epilepsy patients. AB - PURPOSE: (R)-[(11)C]verapamil is a new PET tracer for P-glycoprotein-mediated transport at the blood-brain barrier. For kinetic analysis of (R) [(11)C]verapamil PET data the measurement of a metabolite-corrected arterial input function is required. The aim of this study was to assess peripheral (R) [(11)C]verapamil metabolism in patients with temporal lobe epilepsy and compare these data with previously reported data from healthy volunteers. METHODS: Arterial blood samples were collected from eight patients undergoing (R) [(11)C]verapamil PET and selected samples were analysed for radiolabelled metabolites of (R)-[(11)C]verapamil by using an assay that measures polar N demethylation metabolites by solid-phase extraction and lipophilic N-dealkylation metabolites by HPLC. RESULTS: Peripheral metabolism of (R)-[(11)C]verapamil was significantly faster in patients compared to healthy volunteers (AUC of (R) [(11)C]verapamil fraction in plasma: 29.4 +/- 3.9 min for patients versus 40.8 +/ 5.0 min for healthy volunteers; p < 0.0005, Student's t-test), which resulted in lower (R)-[(11)C]verapamil plasma concentrations (AUC of (R)-[(11)C]verapamil concentration, normalised to injected dose per body weight: 25.5 +/- 2.1 min for patients and 30.5 +/- 5.9 min for healthy volunteers; p = 0.038). Faster metabolism appeared to be mainly due to increased N-demethylation as the polar [(11)C]metabolite fraction was up to two-fold greater in patients. CONCLUSIONS: Faster metabolism of (R)-[(11)C]verapamil in epilepsy patients may be caused by hepatic cytochrome P450 enzyme induction by antiepileptic drugs. Based on these data caution is warranted when using an averaged arterial input function derived from healthy volunteers for the analysis of patient data. Moreover, our data illustrate how antiepileptic drugs may decrease serum levels of concomitant medication, which may eventually lead to a loss of therapeutic efficacy. PMID- 17846770 TI - A case of ABL deletion in a patient with precursor B cell lymphoblastic leukemia. PMID- 17846769 TI - Intra-individual comparison of p-[123I]-iodo-L-phenylalanine and L-3-[123I]-iodo alpha-methyl-tyrosine for SPECT imaging of gliomas. AB - OBJECTIVES: Radioactive amino-acids accumulate in gliomas even with an intact blood-brain-barrier. L-3-[(123)I]-iodo-alpha-methyl-tyrosine (IMT) is well established for SPECT imaging of gliomas. Recently, we introduced p-[(123)I]-iodo L-phenylalanine (IPA) for the characterisation of brain lesions. This study compares both tracers in glioma patients. METHODS: Eleven patients with gliomas (1 WHO grade 1, 5 grade 2, 1 grade 3, 2 grade 4 gliomas, 1 unconfirmed upgrading and 1 post-therapeutic non-neoplastic lesion) underwent SPECT imaging with IPA (early and delayed acquisitions at 30 min and 3 h) and IMT (early only). Maximum tumour-to-brain ratios (TBR) were calculated using region-of-interest analysis to assess uptake of IMT and IPA. Imaging results were compared to histopathological findings. RESULTS: Early TBRs of IMT and IPA were strongly correlated (r = 0.828, p = 0.002). TBRs were higher for IMT than IPA (1.95+/-0.50 versus 1.79+/-0.42; p < 0.05), but independent from tumour cell density (p > 0.1). Visual interpretation by different observers was more concordant for IMT-SPECT than IPA SPECT (kappa 1.0 versus 0.774). No differences in early TBRs were observed between low-grade and high-grade gliomas for IMT (1.97+/-0.53 versus 2.21+/-0.44, p > 0.5) or IPA (1.70+/-0.23 versus 2.21+/-0.56, p = 0.167) with a trend to higher TBRs in low-grade tumours for IMT (p = 0.093). In contrast to the known wash-out of IMT, we observed persistent accumulation of IPA in gliomas. CONCLUSIONS: IPA shows lower TBRs than IMT, especially in low-grade tumours, so IMT should be preferred for the delineation of low-grade gliomas by SPECT imaging. Due to its prolonged retention, however, IPA remains promising for therapeutic use in gliomas after labelling with I-131. PMID- 17846768 TI - In vivo amyloid imaging with PET in frontotemporal dementia. AB - BACKGROUND: N-methyl[11C]2-(4'methylaminophenyl)-6-hydroxy-benzothiazole (PIB) is a positron emission tomography (PET) tracer with amyloid binding properties which allows in vivo measurement of cerebral amyloid load in Alzheimer's disease (AD). Frontotemporal dementia (FTD) is a syndrome that can be clinically difficult to distinguish from AD, but in FTD amyloid deposition is not a characteristic pathological finding. PURPOSE: The aim of this study is to investigate PIB retention in FTD. METHODS: Ten patients with the diagnosis of FTD participated. The diagnosis was based on clinical and neuropsychological examination, computed tomography or magnetic resonance imaging scan, and PET with 18 Fluoro-2-deoxy-d glucose (FDG). The PIB retention, measured in regions of interest, was normalised to a reference region (cerebellum). The results were compared with PIB retention data previously obtained from 17 AD patients with positive PIB retention and eight healthy controls (HC) with negative PIB retention. Statistical analysis was performed with a students t-test with significance level set to 0.00625 after Bonferroni correction. RESULTS: Eight FTD patients showed significantly lower PIB retention compared to AD in frontal (p < 0.0001), parietal (p < 0.0001), temporal (p = 0.0001), and occipital (p = 0.0003) cortices as well as in putamina (p < 0.0001). The PIB uptake in these FTD patients did not differ significantly from the HC in any region. However, two of the 10 FTD patients showed PIB retention similar to AD patients. CONCLUSION: The majority of FTD patients displayed no PIB retention. Thus, PIB could potentially aid in differentiating between FTD and AD. PMID- 17846765 TI - Multimodality imaging of the HER-kinase axis in cancer. AB - The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases controls critical pathways involved in epithelial cell differentiation, growth, division, and motility. Alterations and disruptions in the function of the HER-kinase axis can lead to malignancy. Many therapeutic agents targeting the HER-kinase axis are approved for clinical use or are in preclinical/clinical development. The ability to quantitatively image the HER-kinase axis in a noninvasive manner can aid in lesion detection, patient stratification, new drug development/validation, dose optimization, and treatment monitoring. This review summarizes the current status in multimodality imaging of the HER-kinase axis using PET, SPECT, optical, and MR imaging. The targeting ligands used include small-molecule tyrosine kinase inhibitors, peptides, proteins, antibodies, and engineered antibody fragments. EGFR and HER2 imaging have been well documented in the past, and imaging of HER3, HER4, HER heterodimers, and HER-kinase mutants deserves significant research effort in the future. Successful development of new HER-kinase-targeted imaging agents with optimal in vivo stability, targeting efficacy, and desirable pharmacokinetics for clinical translation will enable maximum benefit in cancer patient management. PMID- 17846771 TI - Long-term propylthiouracil use and acute myeloid leukemia: a case report and review of the literature. PMID- 17846772 TI - Rapid detection of BCR-ABL fusion genes using a novel combined LUX primer, in cell RT-PCR and flow cytometric method. AB - Currently, quantitative and semiquantitative assays for minimal residual disease detection include fluorescence in situ hybridisation, multiparameter flow cytometric immunophenotyping and real-time quantitative polymerase chain reaction (RQ-PCR). We have developed a new approach to detect hybrid breakpoint cluster region and Abelson proto-oncogene (BCR-ABL) transcripts inside suspension cells using in situ RT-PCR and light upon extension (LUX) primer, followed by rapid quantitative analysis with flow cytometry. After cellular permeabilization and fixation of single cell suspension, the neoplastic mRNA was reverse transcribed and amplified by PCR with LUX primer. The results demonstrated that a strong positive yellow-green signal was observed in 99-100% cells of K562 cell line, only the red nucleus was detected in NB4 cell line and normal controls. The technique has been utilised to study 12 patients with chronic myeloid leukemia, and the results were compared with those of BCR-ABL fusion mRNA by RT-PCR and BCR ABL fusion gene of the interphase cells by fluorescence in situ hybridization (FISH). In the five diagnosed patients, 90-98% cells were strongly positive. Four patients, including three patients treated with interferon-alpha and hydroxyurea and one patient treated with imatinib mesylate, had 26-82.5% positive cells. Three patients treated with imatinib mesylate were negative. The in situ RT-PCR results demonstrated complete concordance with the results of I-FISH and RT-PCR. A fluorescence signal was detectable at 1/10(4) cells and became negative below this threshold with flow cytometry. The results of the present study suggest that (1) LUX primers can be used to efficiently detect BCR-ABL fusion mRNA by in-cell RT-PCR; (2) the novel technique is a specific and sensitive way of detecting fusion gene with potential clinical usefulness. PMID- 17846773 TI - Rapid complete remission in multiple myeloma with bortezomib/thalidomide/dexamethasone combination therapy following development of tumor lysis syndrome. PMID- 17846775 TI - [Spitz nevus vs 'spitzoid' malignant melanoma. A diagnostic dilemma?]. AB - Data from the literature and histopathological findings in six personal cases are used to illustrate criteria that can be applied in differential diagnosis between a Spitz nevus and a spitzoid variant of malignant melanoma. The diagnostic term 'atypical Spitz tumor' is explained; it is used to describe a morphological "grey zone" in which it is not possible to differentiate with adequate certainty between a Spitz nevus and a spitzoid malignant melanoma. PMID- 17846776 TI - [Uncommon variants of malignant melanocytic neoplasms]. AB - Benign and malignant melanocytic neoplasms are relatively frequent and show a broad morphological heterogeneity. The spectrum of malignant melanomas comprises the four main types, superficial spreading malignant melanoma, nodular malignant melanoma, lentigo-maligna melanoma and acrolentiginous malignant melanoma. In addition the rare spitzoid malignant melanoma, desmoplastic malignant melanoma as well as some unusual variants of malignant melanoma can be distinguished. The latter include nevoid malignant melanoma, a form of malignant melanoma resembling benign melanocytic nevi, animal type malignant melanoma, an atypical melanocytic neoplasm with numerous melanophages and prominent melanosis resembling an atypical epithelioid blue naevus as well as regressive malignant melanoma, and representing a questionably distinct entity, balloon cell and signet-ring malignant melanomas, melanoma types with degenerative clear cell changes, as well as myxoid and osteogenic malignant melanomas that are characterized by unusual stromal changes. PMID- 17846774 TI - Infection and glomerulonephritis. AB - Glomerular injury, occurring either as primary glomerular disease or as part of a systemic disease process, is usually a result of immune-mediated mechanisms. The morphologic reaction pattern has a diverse spectrum of appearance, ranging from normal by light microscopy in minimal change disease to crescentic forms of glomerulonephritis, with conspicuous disruption of the normal glomerular morphology. The mechanisms of glomerular immune deposit formation include trapping of circulating antigen-antibody complexes and the in situ formation of immune complexes within the glomerulus. While the majority of postinfectious immune-complex-mediated glomerulonephritides are believed to result from the deposition of circulating antigen-antibody complexes, preformed outside of the kidney and secondarily deposited in the kidney, the notion of forming in situ antigen-antibody complexes to either planted antigens or to integral structural components of the glomerulus, through "cross-reacting" autoimmune reactions, is gaining popularity in a variety of forms of glomerulonephritides. Patients with HIV infection may develop a spectrum of renal pathology, the glomerular manifestations of which include both antigen-antibody complex and nonimmune complex-mediated pathogenetic mechanisms. Similarly, patients with Streptococcal infections, Hepatitis B virus, or Hepatitis C virus infection may develop a spectrum of glomerulonephritides, which are predominantly immune-complex mediated. Therapy for glomerular diseases due to HIV, hepatitis B, or C virus infections remains a challenge. PMID- 17846777 TI - Evaluation of the efficacy of therapeutic ultrasound on bone mineral density in postmenopausal period. AB - Therapeutic ultrasound is a frequently used modality in the practice of physical therapy. However, its effects on osteoporosis (OP) are not clear. We investigate the effect of therapeutic ultrasound on bone mineral density (BMD). We examined retrospectively 1,610 postmenopausal patients' data and we created two groups. The treatment group consisted of 36 patients who have been applied only the ultrasound treatment and the control group consisted of 38 patients who have never received any kind of physical treatment. Both of two groups have never received OP treatment. The mean values of BMD showed no significant difference between the treatment and control groups. Patients' BMD values, within the treatment group, were compared according to the treatment application region. There was no significant difference among groups. We determined that the ultrasound application has no effect on BMD. However, we consider that therapeutic ultrasound will help to decrease the skeletal system related complaints of the patients, improve their exercise capacity, and decrease the risk of osteoporosis. PMID- 17846778 TI - Etanercept and adalimumab treatment in patients with rheumatoid arthritis and spondyloarthropathies in clinical practice: adverse events and other reasons leading to discontinuation of the treatment. AB - In the present study, we determined from a single-center data the treatment continuation, discontinuation and reasons for discontinuation in the patients with active rheumatoid arthritis (RA) or spondyloarthropathies (SpA) who were treated with etanercept or adalimumab. All RA and SpA patients, who were treated with etanercept (n = 53) or adalimumab (n = 43) as their first biological treatment according to national guidelines in the Center for Rheumatic Diseases, Tampere University Hospital during the years 1999-2005, were analyzed at baseline and after 1-year treatment. The treatment was regarded ineffective if the clinical response was lower than ACR50 in RA or the reduction of BASDAI was lower than 50% or 2 cm in SpA. After 1 year, the continuation rate was 74% with etanercept and 60% with adalimumab. Mean prednisolone dose among continuers was diminished by 52% in etanercept-treated patients and by 44% in adalimumab-treated patients. During 1-year follow-up, 14 (26%) of the etanercept-treated patients and 17 (40%) of the adalimumab-treated patients discontinued the medication. Eleven patients were regarded as poor responders, seven in etanercept group and four in adalimumab group. Adverse events (mainly infections and injection reactions) caused six discontinuations in etanercept-treated group and 11 discontinuations in adalimumab-treated group. Etanercept was discontinued due to other adverse event in two patients: in one patient due to adenocarcinoma of ovary and in one patient due to drug-related leukopenia. One patient treated with adalimumab developed clinical and immunological features of systemic lupus erythematosus (SLE). In the present study, etanercept and adalimumab treatments were started in patients who had active RA or SpA despite ongoing treatment with combinations of traditional disease modifying antirheumatic drugs (DMARDs). Thirty-nine (74%) patients and twenty-six (60%) patients achieved at least 50% response when etanercept or adalimumab was added to their earlier DMARD treatment. Adverse events (mainly infections and injection reactions) were in line with previous reports. Three rare adverse events were reported: one patient with ovarial carcinoma, one with leukopenia and one with features of drug-induced SLE. PMID- 17846779 TI - [Botulinum toxin injection for production of ptosis]. AB - Selective muscles can be paralysed or weakened for a limited time period using botulinum toxin type A. The upper eyelid muscles can be a target, leading to a temporary protective ptosis. In this report we discuss indications for this application, describe how to perform the injection, and present results. The procedure is safe and effective. PMID- 17846780 TI - Further characterization of an aversive learning task in Drosophila melanogaster: intensity of the stimulus, relearning, and use of rutabaga mutants. AB - Various learning tasks have been described in Drosophila melanogaster, flies being either tested in groups or at the individual level. Le Bourg and Buecher (Anim Learn Behav 33:330-341, 2002) have designed a task at the individual level: photopositive flies crossing a T-maze learn to prefer the dark exit when the lighted one is associated with the presence of aversive stimuli (humidity and quinine). Previous studies have reported various results (e.g. no effect of age) and the present article further characterizes this task by studying the possible effects of: (1) the intensity of the stimuli (quantity of water or concentration of quinine), (2) various delays between two learning sessions on the learning score at the second session, (3) the rutabaga learning mutation on the learning score. More concentrated quinine solutions increased learning scores but the quantity of water had no effect. Learning scores at the second session were higher with shorter delays between the two learning sessions and retrograde amnesia could decrease this memory score. rutabaga mutants showed learning deficits as in experiments testing groups of flies. This learning task could particularly be used to verify whether learning mutants isolated after experiments testing flies in groups display similar deficits when tested at the individual level. PMID- 17846781 TI - The efficacy of diltiazem and glyceryltrinitrate for the medical management of chronic anal fissure: a meta-analysis. AB - OBJECTIVE: The objective of this review is to systematically analyze the prospective randomized controlled trials on the effectiveness of diltiazem (DTZ) and glyceryltrinitrate (GTN) for the pharmacological management of chronic anal fissure (CAF). MATERIALS AND METHODS: A systematic review of the literature was undertaken. Prospective randomized controlled trials on the effectiveness of DTZ for the management of CAF were selected according to specific criteria and analyzed to generate summative data. RESULTS: Five studies encompassing 263 patients with CAF were retrieved from the electronic databases. Only two randomized controlled trials on 103 patients qualified for the meta-analysis. There were 53 patients in the DTZ group and 50 patients in the GTN group. Both DTZ and GTN were equally effective for the treatment of CAF (random-effect model risk ratio [RR] 0.29 [90.06-1.33] 95% confidence interval [CI], z=0.62, p=0.536). However, there was significant heterogeneity between the trials. GTN was associated with higher side effects rate (fixed-effect model RR 0.45 [0.28-0.73] 95% CI, z= -3.22, p=0.001) and higher headache rate (fixed-effect model RR 0.33 [0.17-0.64] 95% CI, z= -3.27, p=0.001) as compared to DTZ. There was no statistically significant recurrence rate of CAF between two pharmacotherapies (fixed-effect model RR 0.66 [0.18-2.41] 95% CI, z= -0.62, p=0.535). CONCLUSION: Both DTZ and GTN are equally effective and can be used for the management of CAF. However, GTN is associated with a higher rate of side effects (headache/anal irritation), and it should be replaced by DTZ. The recurrence rate of CAF after the use of both pharmacotherapies is equal. PMID- 17846782 TI - Recurrent facial nerve paralysis: an unusual presentation of fibrous dysplasia of the temporal bone. AB - Facial nerve paralysis (FNP) is a rare occurrence in fibrous dysplasia (FD) of the temporal bone (FDTB). Eight such cases have been described in the literature. In none of these cases was the FNP the presenting symptom, and in all, a direct etiology for the paralysis was identified. We present the first case of recurrent, unilateral FNP as the sole otological manifestation of FDTB. We discuss possible etiological factors for the paralysis favoring a compressive, transient ischemia of the facial nerve. The authors suggest adding FDTB to the differential diagnosis of recurrent FNP. PMID- 17846783 TI - Influence of cadence, power output and hypoxia on the joint moment distribution during cycling. AB - The purpose of this study was to use a hypoxic stress as a mean to disrupt the normal coordinative pattern during cycling. Seven male cyclists pedalled at three cadence (60, 80, 100 rpm) and three power output (150, 250, 350 W) conditions in normoxia and hypoxia (15% O2). Simultaneous measurements of pedal force, joint kinematics, % oxyhaemoglobin saturation, and minute ventilation were made for each riding condition. A conventional inverse dynamics approach was used to compute the joint moments of force at the hip, knee, and ankle. The relative contribution of the joint moments of force with respect to the total moment was computed for each subject and trial condition. Overall, the ankle contributed on average 21%, the knee 29% and the hip 50% of the total moment. This was not affected by the relative inspired oxygen concentration. Results showed that the relative ankle moment of force remained at 21% regardless of manipulation. The relative hip moment was reduced on average by 4% with increased cadence and increased on average by 4% with increased power output whereas the knee moment responded in the opposite direction. These results suggest that the coordinative pattern in cycling is a dominant characteristic of cycling biomechanics and remains robust even in the face of arterial hypoxemia. PMID- 17846784 TI - The gene doublesex of Anastrepha fruit flies (Diptera, Tephritidae) and its evolution in insects. AB - The doublesex (dsx) gene of several Anastrepha species was isolated and characterised. Its molecular organisation was found to be the same in all the species examined. This gene is composed of four exons: Exons 1 and 2 are common to both sexes, exon 3 is female specific, and exon 4 is male specific. It codes for both the female DsxF and male DsxM proteins, corresponding to the sex specific splicing product of its primary transcript; male-specific splicing is the default mode. A comparison of the Dsx proteins of different Anastrepha species with those of other insects showed them to be very similar. Molecular evolutionary analysis (both at the nucleotide and amino acid levels) of dsx in different insects revealed a topology in good agreement with their owners' taxonomic relationships. The great majority of the nucleotide changes detected in the dsx gene of the analysed species were significantly synonymous, evidence that strong purifying selection has acted on dsx so that the functional structure of the Dsx proteins is preserved. However, the common region of DsxF and DsxM proteins appeared to be the main target for selection acting upon the long-term evolution of gene dsx. PMID- 17846785 TI - Altered expression of desmocollin 3, desmoglein 3, and beta-catenin in oral squamous cell carcinoma: correlation with lymph node metastasis and cell proliferation. AB - Desmocollin 3 (Dsc3) and desmoglein 3 (Dsg3) are both transmembrane glycoproteins that belong to the cadherin family of calcium-dependent cell adhesion molecules. beta-Catenin is a member of the cadherin-catenin complex that mediates homotypic cell-cell adhesion and is also an important molecule in the wnt signaling pathway. In this study, we examined the simultaneous expression level of Dsc3, Dsg3, and beta-catenin in oral squamous cell carcinomas (OSCCs) and normal oral epithelia using immunohistochemistry. There was a significant correlation (p < 0.05) among the following variables in OSCCs: reduced or loss of expression of Dsc3, Dsg3, and beta-catenin compared to normal oral epithelium, reduced or loss of expression of Dsc3 and histological grade (moderately or poorly differentiated), and reduced or loss of expression of beta-catenin and lymph node metastasis. Furthermore, a positive correlation was found between reduced or loss of beta-catenin staining and reduced or loss of Dsc3 staining in lymph node metastatic cancer tissue (r = 0.734, p < 0.05). These results suggest an abnormal expression of Dsc3, Dsg3, and beta-catenin induced in the progression of oral carcinomas and that the Dsc3 expression level might be related to the regulation of beta-catenin in lymph node metastasis and cell proliferation in OSCCs. PMID- 17846786 TI - Acute metabolic decompensation and sudden death in Barth syndrome: report of a family and a literature review. AB - Barth syndrome presents in infancy with hypotonia, dilated cardiomyopathy, and neutropenia. We report a patient whose family history included two males who had died suddenly at the age of 15 days and 2 years, respectively. The index case presented with acute metabolic decompensation at 13 days of age. Within 8 h of presenting with metabolic acidosis (pH 7.13), lactic acidemia (18.5 mmol/l), hyperammonemia (375 microg/dl), hypoglycemia (25 mg/dl), and coagulopathy, the patient developed respiratory failure and required intubation. The diagnosis was established by the presence of left ventricular noncompaction and molecular analysis (c.C153G or Y51X mutation of the TAZ gene). The gene product, taffazin, is a homologue of the glycerolipid transferases involved in the phospholipid metabolism as tetralinoleoyl-cardiolipin, a component of the mitochondrial inner membrane. In conclusion, mutations in taffazin impair mitochondrial respiratory chain complexes, which may results in the acute metabolic decompensation and sudden death; cardiac transplantation is the only possibility at the present time. PMID- 17846787 TI - SCC-112 gene is involved in tumor progression and promotes the cell proliferation in G2/M phase. AB - PURPOSE: SCC-112 is a novel cell cycle-related gene and differentially expressed in cancers. Suggesting the complex role of SCC-112 might be existent in cell proliferation and tumor development. The relative research on SCC-112 has been few so far. This study is attempted to explore the role of SCC-112 in tumorigenesis. EXPERIMENTAL DESIGN: RT-PCR and western blot were performed on seven tumor-normal paired tissues and nine cell lines. Immunohistochemistry was carried out for analyzing the expression of SCC-112 in nasopharyngeal tissues. 293T and three nasopharyngeal cell lines were transfected with expression vector (pCMV-SPORT6-SCC-112) or its siRNA. Cell proliferation was examined by MTT and clone formation experiments. Immunoprecipitation determined the interacted protein of SCC-112, and FACS detected cell cycle parameter on cells treated with synchronized reagent. RESULTS: SCC-112 ( approximately 150 kDa) is up-regulated in tumor tissue as compared to the corresponding normal tissue and was detected in the tested cell lines. Overexpression of SCC-112 ( approximately 150 kDa) in 293T and three nasopharyngeal cell lines promoted cell proliferation and clone formation while downregulation of SCC-112 ( approximately 150 kDa) in these cells resulted in the opposite. Moreover, SCC-112 was found to interact with p63 and overexpression of SCC-112 up-regulated p63 expression. SCC-112 expression level positively correlated with cells in G2/M phase. CONCLUSIONS: These findings suggest that SCC-112 improve cell proliferation and contributes to tumorigenesis by interacting with p63 and promoting cell cycling. SCC-112 might be an alternative target in tumor biomarking and mechanistic investigation. PMID- 17846788 TI - Multilocular cystic renal cell carcinoma: an experience of clinical management for 31 cases. AB - In order to increase our knowledge and understanding about multilocular cystic renal cell carcinoma (MCRCC), including diagnosis, surgical management, pathologic and prognostic characteristics, clinical data of patients who suffered with MCRCC were reviewed retrospectively. From 1998 to 2005, among 770 patients diagnosed with renal cell carcinoma (RCC) at our institute, 31 cases (4.0%) were identified as MCRCC. The average age of patients suffered with RCC and MCRCC was 58.1 +/- 3.6 and 45.9 +/- 2.7, respectively (P < 0.01), whereas the gender ratio of male to female in RCC and MCRCC is 2.12:1 and 2.88:1(P < 0.01). Surprisingly, 28 of those 31 renal masses (90.3%) were first discovered on the radiographic image, and the size of tumors in maximum diameter ranged from 1.7 to 11.0 cm (mean 4.1 +/- 2.2 cm). All those patients were treated with open nephrectomy, including 21 radical and 10 partial. The stages of tumor were classified as pT1N0M0, pT2N0M0, and pT3bN0M0 following the 1997 criteria of tumor-node metastasis (TNM) classification in the number of 27(87.1%), 3(9.7%) and 1(3.2%), respectively. By contrast, according to the tumor nuclear grading system, those tumors were classified as Grades 1 and 2 in 13 (42%) and 18 patients (58%), respectively. Only 29 cases from those patients have been followedup for a period of 9 to 81 months so far (mean 32.6 +/- 11), while no tumor recurrence occurred except for 1 case who died of causes other than MCRCC. In general, MCRCC is a frequent subtype of RCC in the clinic. A nephron-sparing procedure should be considered in the preoperative plan when a complex multicystic renal mass with enhanced density is observed. PMID- 17846789 TI - Determining the adaptation potential of entomopathogenic nematode multiplication of Heterorhabditis riobravus and Steinernema carpocapsae (Rhabditida: Heterorhabditidae, Steinernematidae) in larvae of Alphitobius diaperinus (Coleoptera: Tenebrionidae) and Galleria mellonella (Lepidoptera: Pyralidae). AB - Our objective was to determine the mean production of entomopathogenic nematodes (EPNs) infective juveniles (IJs) from Alphitobius diaperinus and Galleria mellonella larvae and the possible morphometric changes of emergent IJs. Heterorhabditis riobravus and Steinernema carpocapsae nematodes were placed on 20 larvae of each host individually located in Petri dishes, which were maintained in an environmental control chamber. After death, each larva was individually transferred to White traps where they remained for a maximum of 20 days in environmental control chambers. With IJ multiplication, the water from each trap was separately collected, emergent IJs were counted, and mean production was calculated for each host species. Relative populations of each nematode species emerging from each host were randomly selected and miscegenated. Then, 50 IJs from each host/species were randomly selected for morphometric studies. Significant difference was seen between the two EPN species for mean IJ production values from G. mellonella larvae (P = 0.0048) but not from A. diaperinus larvae (P = 0.8883). Significant differences were also seen in total body length and width between the emergent H. riobravus and S. carpocapsae IJs (P = 0.0002). PMID- 17846790 TI - Differences in protein profiles of the isolates of Entamoeba histolytica and E. dispar by surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS) ProteinChip assays. AB - Surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) ProteinChip assays with weak cationic exchange chips were used for protein profiling of different isolates of Entamoeba histolytica and E. dispar. When SELDI-TOF MS spectra of cell lysates from E. histolytica strain HM-1:IMSS were compared with those from four other laboratory strains (200:NIH, HK-9, DKB, and SAW755CR) grown under the same culture conditions, different peak patterns of SELDI-TOF MS were observed among these strains, independent of their zymodeme types. Similarly, five Japanese isolates of E. histolytica grown under the same culture conditions revealed different peak patterns among themselves. The SELDI TOF MS spectra of cell lysates from two isolates of E. dispar strain AS16IR and CYNO 09:TPC showed the presence of peaks specific for E. dispar isolates and the absence of peaks common to E. histolytica isolates. This is not only the first use of SELDI-TOF MS ProteinChip technology for protein profiling of different strains of Entamoeba but also the use for parasitic protozoa. The SELDI-TOF MS spectra show a realistic view of proteins with a biological status of E. histolytica and E. dispar isolates, contributing to show their phenotypic differences of proteins and provide a unique means of distinguishing them. PMID- 17846791 TI - A checklist of metazoan parasites of fish from Tres Palos Lagoon, Guerrero, Mexico. AB - An extensive survey of helminth parasites in fish species from Tres Palos Lagoon, in Guerrero, Mexico, resulted in identification of 39 metazoan parasite species (37 helminth and 2 crustaceans) in 13 fish species (n = 1,498). Specimen collection in this coastal lagoon was done between April 2000 and November 2003. Digenean species (18, 8 adult and 10 metacercariae) dominated the parasite fauna. The most widespread species of parasite were: Contracaecum sp. (Nematoda), Pseudoacanthostomum panamense, Austrodiplostomum compactum, Ascocotye (Phagicola) longa (Digenea), Neoechinorhynchus golvani (Acanthocephala), Ergasilus sp. (Copepoda), and Argulus sp. (Branchiura). Parasite fauna species composition exhibited a clear freshwater influence as 56.4% (22 of 39) of the identified species have a freshwater distribution in Mexico. For 32 of the parasite species, this report constitutes the first geographical host record for Tres Palos Lagoon, Guerrero, Mexico. PMID- 17846792 TI - Kudoa unicapsula n. sp. (Myxosporea: Kudoidae) a parasite of the Mediterranean mullets Liza ramada and L. aurata (Teleostei: Mugilidae). AB - A new multivalvulid myxozoan parasite, Kudoa unicapsula n. sp., is described from the intestinal mesentery, intestine and pyloric caeca of the thin-lipped grey mullet Liza ramada (Risso 1826) and the golden grey mullet L. aurata (Risso, 1810) from the Mediterranean coastal waters of Spain. It is characterized by the presence of elongated, rice corn-like white cysts of 0.47-0.56 x 0.18-0.38 mm, filled with tetracapsulate, slightly asymmetric spores, rectangular in apical view and tear-shaped in lateral view with four polar capsules of considerably different size and slightly unequal spore valves with rounded edges, overlapping each other on the apex of the spore. One large polar capsule includes a polar filament coiled in two to three turns, and the other three polar capsules, which are very small, posses only a rudimental filament. Both light and electron microscopy data showed that this species differs from all previously described Kudoa spp. with unequal polar capsules. The molecular analysis based on 18S and 28S ribosomal deoxyribonucleic acid DNA sequence data of K. unicapsula n. sp. indicates a close relationship and thus phylogenetic clustering together with K. trifolia, a myxozoan from the same host and the same geographical location. PMID- 17846793 TI - The timing of sulfadiazine therapy impacts the reactivation of latent Toxoplasma infection in IRF-8-/- mice. AB - The process of reactivation of latent infection with Toxoplasma gondii in immunosuppressed hosts is yet not fully understood. In the past, a number of murine models of reactivation in immunocompromised mice have been described using sulfadiazine to establish latent infection before withdrawal and subsequent reactivation. We studied the process of reactivation in brains of mice with a targeted mutation in the interferon-regulatory factor (IRF)-8 gene after withdrawal of sulfadiazine therapy. IRF-8(-/-) mice were orally infected with five cysts of the ME 49 strain of T. gondii. To allow establishment of latent infection with cyst formation, mice were treated with sulfadiazine starting either 3, 5, 6, or 7 days postinfection. Sulfadiazine was withdrawn after 14-21 days to allow reactivation. We observed that timing of sulfadiazine therapy had a marked impact on the course of infection and reactivation. Mice treated late after infection (days 5-7) showed increased mortality and decreased time to death compared to mice treated early after infection (group A). In the blood of mice with late (days 5-7) but not early (day 3) initiation of treatment, T. gondii specific deoxyribonucleic acid was detected by polymerase chain reaction. Using double staining with stage-specific antibodies, tachyzoites were detectable in brains of mice with late initiation of sulfadiazine treatment but rarely within cysts thus indicating continued invasion of parasites across the blood-brain barrier. Intracerebral cyst rupture or bradyzoite-tachyzoite conversion was not detectable in IRF-8(-/-) mice when sulfadiazine therapy was initiated late after infection. These results indicate that continued invasion of tachyzoites rather than reactivation of latent cerebral infection impacts the course of infection in this model of reactivated toxoplasmosis. In conclusion, the timing of sulfadiazine therapy is of utmost importance for the course of infection in immunocompromised mice. PMID- 17846795 TI - Immunogenicity of human embryonic stem cells. AB - Human embryonic stem cells (HESC) are pluripotent stem cells isolated from the inner cell mass of human blastocysts. With the first successful culturing of HESC, a new era of regenerative medicine was born. HESC can differentiate into almost any cell type and, in the future, might replace solid organ transplantation and even be used to treat progressive degenerative diseases such as Parkinson's disease. Although this sounds promising, certain obstacles remain with regard to their clinical use, such as culturing HESC under well-defined conditions without exposure to animal proteins, the risk of teratoma development and finally the avoidance of immune rejection. In this review, we discuss the immunological properties of HESC and various strategic solutions to circumvent immune rejection, such as stem cell banking, somatic cell nuclear transfer and the induction of tolerance by co-stimulation blockade and mixed chimerism. PMID- 17846794 TI - Molecular and phylogenetic analysis of MADS-box genes of MIKC type and chromosome location of SEP-like genes in wheat (Triticum aestivum L.). AB - Transcription factors encoded by MIKC-type MADS-box genes control many important functions in plants, including flower development and morphogenesis. The cloning and characterization of 45 MIKC-type MADS-box full-length cDNA sequences of common wheat is reported in the present paper. Wheat EST databases were searched by known sequences of MIKC-type genes and primers were designed for cDNA cloning by RT-PCR. Full-length cDNAs were obtained by 5' and 3' RACE extension. Southern analysis showed that three copies of the MIKC sequences, corresponding to the three homoeologous genes, were present. This genome organization was further confirmed by aneuploid analysis of six SEP-like genes, each showing three copies located in different homoeologous chromosomes. Phylogenetic analysis included the wheat MIKC cDNAs into 11 of the 13 MIKC subclasses identified in plants and corresponding to most genes controlling the floral homeotic functions. The expression patterns of the cDNAs corresponding to different homeotic classes was analysed in 18 wheat tissues and floral organs by RT-PCR, real time RT-PCR and northern hybridisation. Potential functions of the genes corresponding to the cloned wheat cDNAs were predicted on the basis of sequence homology and comparable expression pattern with functionally characterized MADS-box genes from Arabidopsis and monocot species. PMID- 17846796 TI - Radial glia and neural stem cells. AB - During the last decade, the role of radial glia has been radically revisited. Rather than being considered a mere structural component serving to guide newborn neurons towards their final destinations, radial glia is now known to be the main source of neurons in several regions of the central nervous system, notably in the cerebral cortex. Radial glial cells differentiate from neuroepithelial progenitors at the beginning of neurogenesis and share with their ancestors the bipolar shape and the expression of some molecular markers. Radial glia, however, can be distinguished from neuroepithelial progenitors by the expression of astroglial markers. Clonal analyses showed that radial glia is a heterogeneous population, comprising both pluripotent and different lineage-restricted neural progenitors. At late-embryonic and postnatal stages, radial glial cells give rise to the neural stem cells responsible for adult neurogenesis. Embryonic pluripotent radial glia and adult neural stem cells may be clonally linked, thus representing a lineage displaying stem cell features in both the developing and mature central nervous system. PMID- 17846797 TI - Possible involvement of SDF-1alpha/CXCR4-DPPIV axis in TGF-beta1-induced enhancement of migratory potential in human peritoneal mesothelial cells. AB - We have previously reported that human peritoneal mesothelial cells (HPMCs) express a large amount of dipeptidyl peptidase IV (DPPIV) and that its expression is regulated by a variety of bioactive substances in malignant ascites from ovarian cancer patients. The aim of this study has been to examine the expression and role of the SDF-1alpha/CXCR4-DPPIV axis in HPMCs. We have demonstrated that the expression levels of DPPIV and E-cadherin in HPMCs decrease, following TGF beta1-induced morphological change, in a time- and concentration-dependent manner. Additionally, we show that both SDF-1alpha (a chemokine and substrate for DPPIV) and its receptor, CXCR4, are expressed on HPMCs, and that their expression levels are upregulated by TGF-beta1 treatment, resulting in an increased migratory potential of HPMCs. Furthermore, the migratory potential of HPMCs is significantly enhanced in the presence of SDF-1alpha or DPPIV-specific inhibitor in the wound-healing assay. These results suggest that DPPIV and SDF-1alpha/CXCR4 play crucial roles in regulating the migratory potential of HPMCs, which may be involved in the re-epithelialization of denuded basement membrane at the site of peritoneal injury. PMID- 17846798 TI - Allometric relationships between seed mass and seedling characteristics reveal trade-offs for neotropical gap-dependent species. AB - A seed size-seed number trade-off exists because smaller seeds are produced in greater number but have a lower probability of establishment. This reduced establishment success of smaller-seeded species may be determined by biophysical constraints imposed by scaling rules. Root and shoot diameter, root growth extension rate (RGER) and shoot length at death for dark-grown seedlings are predicted to scale with the cube root of seed embryo and endosperm mass (m). We confirmed this expectation for ten neotropical gap-dependent tree species with an embryo and endosperm dry mass>1 mg. However, for nine smaller seeded species (m<1 mg) with photoblastic germination, root and shoot diameters were larger than expected, and consequently, RGER was slower than expected. The maximum shoot thrust of seedlings from seeds with masses>or=1 mg was comparable to the estimated force required to displace overlying litter, supporting the hypothesis that photoblastic behaviour only occurs in seeds with insufficient shoot thrust to displace overlying leaves. Using the model soil water, energy and transpiration to predict soil drying in small and large gaps, we showed that: (1) gaps that receive a significant amount of direct sunlight will dry more quickly than small gaps that do not, (2) compared to the wet-season, soil that is already dry at depth (i.e. the dry-season) will dry faster after rainfall (this drying would most likely kill seedlings from small seeds) and (3) even during the wet season, dry periods of a few days in large gaps can kill shallow-rooted seedlings. We conclude that the smaller the seed, the more vulnerable its seedling would be to both covering by litter and soil drying because it can only emerge from shallow depths and has a slow RGER. Consequently, we suggest that these allometrically related factors contribute to the reduced establishment success of smaller-seeded species that underpins the seed size-seed number trade off. PMID- 17846799 TI - Untangling the roles of fire, grazing and rainfall on small mammal communities in grassland ecosystems. AB - In grassland systems across the globe, ecologists have been attempting to understand the complex role of fire, grazing and rainfall in creating habitat heterogeneity and the consequences of anthropogenic control of these factors on ecosystem integrity and functioning. Using a South African grassland ecosystem as a model, we investigated the impact of fire and grazing pressure on small mammal communities during three differing periods of a rainfall cycle. Over 2 years, 15,203 trap nights revealed 1598 captures of 11 species (nine rodents, one macroscelid and one insectivore). Results highlighted the importance of the interplay between factors and showed that the role of fire, grazing and rainfall in determining small mammal abundance was species-dependant. While no two species were affected by the same environmental variables, grass cover or height was important to 56% of species. Considered independently, high rainfall had a positive influence on small mammal abundance and diversity, although the lag period in population response was species-specific. High grazing negatively affected overall abundance, but specifically in Mastomys coucha; fire alone had little immediate impact on small mammal diversity. Six months after the fire, vegetation cover had recovered to similar levels as unburned areas, although small mammal diversity and richness were higher in burned areas than unburned areas. Grazing levels influenced the rate of vegetation recovery. In conclusion, low-level grazing and burning can help to maintain small mammal biodiversity, if conducted under appropriate rainfall levels. A too high grazing pressure, combined with fire, and/or fire conducted under drought conditions can have a negative impact on small mammal biodiversity. To maintain small mammal diversity in grassland ecosystems, the combined effects of the previous year's rainfall and existing population level as well as the inhibition of vegetation recovery via grazing pressure need to be taken into consideration before fire management is applied. PMID- 17846800 TI - Geographic and seasonal patterns and limits on the adaptive response to temperature of European Mytilus spp. and Macoma balthica populations. AB - Seasonal variations in seawater temperature require extensive metabolic acclimatization in cold-blooded organisms inhabiting the coastal waters of Europe. Given the energetic costs of acclimatization, differences in adaptive capacity to climatic conditions are to be expected among distinct populations of species that are distributed over a wide geographic range. We studied seasonal variations in the metabolic adjustments of two very common bivalve taxa at European scale. To this end we sampled 16 populations of Mytilus spp. and 10 Macoma balthica populations distributed from 39 degrees to 69 degrees N. The results from this large-scale comprehensive comparison demonstrated seasonal cycles in metabolic rates which were maximized during winter and springtime, and often reduced in the summer and autumn. Studying the sensitivity of metabolic rates to thermal variations, we found that a broad range of Q (10) values occurred under relatively cold conditions. As habitat temperatures increased the range of Q (10) narrowed, reaching a bottleneck in southern marginal populations during summer. For Mytilus spp., genetic-group-specific clines and limits on Q (10) values were observed at temperatures corresponding to the maximum climatic conditions these geographic populations presently experience. Such specific limitations indicate differential thermal adaptation among these divergent groups. They may explain currently observed migrations in mussel distributions and invasions. Our results provide a practical framework for the thermal ecophysiology of bivalves, the assessment of environmental changes due to climate change and its impact on (and consequences for) aquaculture. PMID- 17846801 TI - High failure rate of the interspinous distraction device (X-Stop) for the treatment of lumbar spinal stenosis caused by degenerative spondylolisthesis. AB - The X-Stop interspinous distraction device has shown to be an attractive alternative to conventional surgical procedures in the treatment of symptomatic degenerative lumbar spinal stenosis. However, the effectiveness of the X-Stop in symptomatic degenerative lumbar spinal stenosis caused by degenerative spondylolisthesis is not known. A cohort of 12 consecutive patients with symptomatic lumbar spinal stenosis caused by degenerative spondylolisthesis were treated with the X-Stop interspinous distraction device. All patients had low back pain, neurogenic claudication and radiculopathy. Pre-operative radiographs revealed an average slip of 19.6%. MRI of the lumbosacral spine showed a severe stenosis. In ten patients, the X-Stop was placed at the L4-5 level, whereas two patients were treated at both, L3-4 and L4-5 level. The mean follow-up was 30.3 months. In eight patients a complete relief of symptoms was observed post operatively, whereas the remaining 4 patients experienced no relief of symptoms. Recurrence of pain, neurogenic claudication, and worsening of neurological symptoms was observed in three patients within 24 months. Post-operative radiographs and MRI did not show any changes in the percentage of slip or spinal dimensions. Finally, secondary surgical treatment by decompression with posterolateral fusion was performed in seven patients (58%) within 24 months. In conclusion, the X-Stop interspinous distraction device showed an extremely high failure rate, defined as surgical re-intervention, after short term follow-up in patients with spinal stenosis caused by degenerative spondylolisthesis. We do not recommend the X-Stop for the treatment of spinal stenosis complicating degenerative spondylolisthesis. PMID- 17846802 TI - Consequences of patient position in the radiographic measurement of artificial disc replacement angles. AB - Accurate clinical measurement of spinal range of motion (ROM) is essential in the evaluation of artificial disc performance. The effect of patient placement with respect to the X-ray beam source is yet to be reported and may be an influencing factor in radiographic artificial disc angle measurements. This study aims to evaluate how radiographic patient placement influences artificial disc angle measurements. An anatomically accurate synthetic L4-L5 motion segment was instrumented with an artificial disc and two pins. The instrumented motion segment was mounted onto a frame allowing for independent rotation and elevation while holding the artificial disc angle and anatomical position between L4 and L5 fixed. Analyses included descriptive statistics, evaluation of uncertainty, intra and inter-observer, and a 2-way analysis of variance (ANOVA). The mean angle measurement range at the various positions was 1.26 degrees for the pin, and 2.74 degrees for the artificial disc endplates. The centered patient position had the highest inter- and intra-observer reliability. ANOVA results showed elevation effects to be statistically significant (P = 0.021), and rotational effects to be extremely statistically significant (P < 0.0001) for the pin angles. In terms of the mean artificial disc angle, however, the ANOVA showed a highly statistically significant interaction term (P = 0.002). A significant difference was found in the angle measurements of a fixed artificial disc prosthesis based on a sample of patient radiographic placement positions. Since it is important to assess the success of an artificial disc replacement by evaluating the relatively small ROM present, it is crucial to aim at minimizing the error by placing the patient parallel to the plate with the beam centered not at the mid lumbar spine, but at the level of the arthroplasty, for both flexion and extension views. PMID- 17846803 TI - The use of physical biomodelling in complex spinal surgery. AB - Prior studies have suggested that biomodels enhance patient education, preoperative planning and intra-operative stereotaxy; however, the usefulness of biomodels compared to regular imaging modalities such as X-ray, CT and MR has not been quantified. Our objective was to quantify the surgeon's perceptions on the usefulness of biomodels compared to standard visualisation modalities for preoperative planning and intra-operative anatomical reference. Physical biomodels were manufactured for a series of 26 consecutive patients with complex spinal pathologies using a stereolithographic technique based on CT data. The biomodels were used preoperatively for surgical planning and customising implants, and intra-operatively for anatomical reference. Following surgery, a detailed biomodel utility survey was completed by the surgeons, and informal telephone interviews were conducted with patients. Using biomodels, 21 deformity and 5 tumour cases were performed. Surgeons stated that the anatomical details were better visible on the biomodel than on other imaging modalities in 65% of cases, and exclusively visible on the biomodel in 11% of cases. Preoperative use of the biomodel led to a different decision regarding the choice of osteosynthetic materials used in 52% of cases, and the implantation site of osteosynthetic material in 74% of cases. Surgeons reported that the use of biomodels reduced operating time by a mean of 8% in tumour patients and 22% in deformity procedures. This study supports biomodelling as a useful, and sometimes essential tool in the armamentarium of imaging techniques used for complex spinal surgery. PMID- 17846804 TI - Neurovascular risks of sacral screws with bicortical purchase: an anatomical study. AB - The aim of this cadaver study is to define the anatomic structures on anterior sacrum, which are under the risk of injury during bicortical screw application to the S1 and S2 pedicles. Thirty formaldehyde-preserved human male cadavers were studied. Posterior midline incision was performed, and soft tissues and muscles were dissected from the posterior part of the lumbosacral region. A 6 mm pedicle screw was inserted between the superior facet of S1 and the S1 foramen. The entry point of the S2 pedicle screw was located between S1 and S2 foramina. S1 and S2 screws were placed on both right and the left sides of all cadavers. Then, all cadavers were turned into supine position. All abdominal and pelvic organs were moved away and carefully observed for any injury. The tips of the sacral screws were marked and the relations with the anatomic structures were defined. The position of the sacral screws relative to the middle and lateral sacral arteries and veins, and the sacral sympathetic trunk were measured. There was no injury to the visceral organs. In four cases, S1 screw tip was in direct contact with middle sacral artery. In two cases, S1 screw tip was in direct contact with middle sacral vein. It was observed that the S1 screw tips were in close proximity to sacral sympathetic trunk on both right and the left sides. The tip of the S2 screw was in contact with middle sacral artery on the left side only in one case. It is found that the tip of the S2 screw was closely located with the middle sacral vein in two cases. The tip of the S2 pedicle screw was in contact with the sacral sympathetic trunk in eight cases on the right side and seven cases on the left side. Lateral sacral vein was also observed to be disturbed by the S1 and S2 screws. As a conclusion, anterior cortical penetration during sacral screw insertion carries a risk of neurovascular injury. The risk of sacral sympathetic trunk and minor vascular structures together with the major neurovascular structures and viscera should be kept in mind. PMID- 17846805 TI - [The state of the art in human dental stem cell research]. AB - This review article arranges the current results of stem cell biology for their use in dentistry. There are different types of stem cells, which are applicable for dental treatments. The use of embryonic stem cells, whose possibilities for breeding an artificial tooth were hardly evaluated, is however ethically precarious. On the other side the ethically harmless adult stem cells, which were isolated for example from bone marrow, were little examined for their capability of differentiation into dental tissues. Therefore their forthcoming use in dentistry is rather improbable. However, dental ectomesenchymal stem cells are more promising for dentistry in future. For example dental pulp stem cells (DPSCs) are capable to differentiate into dentin under in vitro conditions. Moreover it is possible to use periodontal ligament (PDL) stem cells and dental follicle precursors for periodontal tissue differentiations in vitro. Recently new populations of stem cells were isolated from the dental pulp and the PDL. These cells distinguish from the initially isolated DPSCs and PDL stem cells in growth and cell differentiation. Therefore stem cell markers are very important for the characterization of dental stem cells. A significant marker for dental stem cells is STRO-1, which is also a marker for bone marrow derived mesenchymal stem cells. Nonetheless dental stem cells are CD45 negative and they express rarely hematopoietic stem cell markers. These research results plead for the participation of dental stem cells in dental practice in future. PMID- 17846807 TI - Polyester non-woven fabric finger cover as a TRUCT Braille reading assistance tool for Braille learners. AB - Transparent resinous ultraviolet-curing type (TRUCT) Braille signs are becoming more and more popular in Japan, especially when they are printed together with visual characters. These signs are made by screen printing, a technique that can be applied to various base materials, such as paper, metal, and plastic. TRUCT Braille signs have begun to be used in public facilities, such as on tactile maps and on handrails. Naturally, it is expected that Braille beginners will utilize these signs. However, it has been pointed out that the friction between the forefinger and the base material may affect reading accuracy and speed. In this study, we developed a finger cover made of soft, thin polyester non-woven fabric to reduce friction during Braille reading. We also carried out a study to investigate the effect of its use. The subjects were 12 Braille learners with acquired visual impairment, who were asked to read randomly selected characters with and without the finger cover. The results showed that most participants could read TRUCT Braille significantly faster and more accurately with a finger cover than without it, regardless of the base material and dot height. This result suggests that wearing the finger cover enables Braille learners to read TRUCT Braille more efficiently. The finger cover can be used as a Braille reading assistance tool for Braille learners. An additional, health-related advantage of the finger cover is that the forefinger remains clean. We expect that the finger cover will be in practical use in Japan within 1 or 2 years. PMID- 17846806 TI - A mathematical tool to generate complex whole body motor tasks and test hypotheses on underlying motor planning. AB - In spite of the complexity of human motor behavior, difficulties in mathematical modeling have restricted to rather simple movements attempts to identify the motor planning criterion used by the central nervous system. This paper presents a novel-simulation technique able to predict the "desired trajectory" corresponding to a wide range of kinematic and kinetic optimality criteria for tasks involving many degrees of freedom and the coordination between goal achievement and balance maintenance. Employment of proper time discretization, inverse dynamic methods and constrained optimization technique are combined. The application of this simulator to a planar whole body pointing movement shows its effectiveness in managing system nonlinearities and instability as well as in ensuring the anatomo-physiological feasibility of predicted motor plans. In addition, the simulator's capability to simultaneously optimize competing movement aspects represents an interesting opportunity for the motor control community, in which the coexistence of several controlled variables has been hypothesized. PMID- 17846808 TI - Adaptive segmentation of cerebrovascular tree in time-of-flight magnetic resonance angiography. AB - Accurate segmentation of the human vasculature is an important prerequisite for a number of clinical procedures, such as diagnosis, image-guided neurosurgery and pre-surgical planning. In this paper, an improved statistical approach to extracting whole cerebrovascular tree in time-of-flight magnetic resonance angiography is proposed. Firstly, in order to get a more accurate segmentation result, a localized observation model is proposed instead of defining the observation model over the entire dataset. Secondly, for the binary segmentation, an improved Iterative Conditional Model (ICM) algorithm is presented to accelerate the segmentation process. The experimental results showed that the proposed algorithm can obtain more satisfactory segmentation results and save more processing time than conventional approaches, simultaneously. PMID- 17846809 TI - A new capnograph based on an electro acoustic sensor. AB - End tidal carbon dioxide measurements with an electro acoustic capnograph prototype have been demonstrated. The aim of this study was to verify that it is possible to obtain an adequate capnogram using the prototype and to investigate the influence of ambient temperature and humidity variations. By simultaneous measurements with a reference capnograph, on subjects performing exercise, hypo- and hyperventilation, P(ET)CO(2) readings from the reference were compared with the output signal from the prototype. The capnogram from the prototype correlated well with the reference in terms of breath time. The first parts of the expiration and inspiration phases were steeper for the reference than the prototype. The output signal from the prototype correlated well with the reference P(ET)CO(2) readings with a correlation coefficient of 0.93 at varied temperature and relative humidity. PMID- 17846813 TI - Applying EMDR on children with PTSD. AB - OBJECTIVE: To find out child-adjusted protocol for eye movement desensitization and reprocessing (EMDR). METHOD: Child-adjusted modification were made in the original adult-based protocol, and within-session measurements, when EMDR was used in a randomized controlled trial (RCT) on thirty-three 6-16-year-old children with post-traumatic stress disorder (PTSD). RESULTS: EMDR was applicable after certain modifications adjusted to the age and developmental level of the child. The average treatment effect size was largest on re-experiencing, and smallest on hyperarousal scale. The age of the child yielded no significant effects on the dependent variables in the study. CONCLUSIONS: A child-adjusted protocol for EMDR is suggested after being applied in a RCT for PTSD among traumatized and psychosocially exposed children. PMID- 17846812 TI - Switching from methylphenidate immediate release to MPH-SODAS in attention deficit/hyperactivity disorder. AB - OBJECTIVE: To assess ADHD symptoms after switching from Methylphenidate Immediate release (MPH-IR) to Methylphenidate Spheroidal Oral Drug Absorption System (MPH SODAS) in clinically stable patients with ADHD and to identify predictors of dissatisfaction with MPH-SODAS. METHODS: This is an 8-week open clinical trial. Patients were assigned to MPH-SODAS according to their pre-study dose of MPH-IR. Assessments at baseline were conducted using the Swanson, Nolan, and Pelham-IV Questionnaire (SNAP-IV), and the Barkley's Side Effect Rating Scale (SERS). Potentials predictors of treatment response were evaluated. RESULTS: From 62 patients, 47 completed the protocol. There was no significant change in the total score at the SNAP-IV (F (1,51.26) = 0.01; P = 0.91) and its subscales scores during the trial. Although no significant effect on the SERS total score (F (1,111.49) = 0.75; P = 0.39) was found, one adult patient with a previous cardiovascular condition presented a hemorrhagic cerebral vascular accident resulting in her obit. Overall, 46 (74.2%) patients reported to be satisfied. No factor assessed predicted dissatisfaction in univariated analyses. CONCLUSION: Results suggested that switching from MPH-IR to MPH-SODAS did not affect stabilization of ADHD symptoms in the majority of patients. MPH prescription in patients with previous cardiovascular conditions must be extremely careful. Further studies with long-acting MPH including larger samples and patients not responsive to MPH-IR are needed especially in countries outside the US. PMID- 17846814 TI - Selective mutism. A school-based cross-sectional study from Turkey. AB - OBJECTIVE: The aim of this study is to examine the prevalence of selective mutism (SM) in Kocaeli, Turkey. METHOD: Kindergarten, first, second and third grade students of all public/private schools within the city were included in the study. "SM screening forms" prepared on basis of DSM-IV were submitted to classroom teachers in all these schools asking whether they had any students meeting such symptoms. RESULTS: About 84.51% of the schools returned forms covering 64,103 children. Five hundred and twenty six of these children were thought to have symptoms of SM by their teachers. After their DSM-IV based clinical evaluation by a child and adolescent psychiatrist, only 21 children were diagnosed as SM. Among the SM group, three were in the kindergarten, 15 were in the first grade and three were in the second grade. Twelve of the children were male and nine were female (male: female ratio is 1.3:1). In this cross-sectional study, 0.83% of children were reported to have SM symptoms by their teachers. After the clinical evaluation of these children, the prevalence rate of SM was found to be 0.033%. PMID- 17846815 TI - Psychopathology in elite rhythmic gymnasts and anorexia nervosa patients. AB - This study investigates current psychopathology and psychological distress in elite rhythmic gymnasts. Due to a strong emphasis on leanness in aesthetic sports and the controversial findings in literature regarding the role of anorexia nervosa (AN) in such sports, we compared elite rhythmic gymnasts (n=51) to inpatients with AN (n=55) as a disease control group and to high school students (n=53) as a "normal" control group. We assessed psychopathology using the Symptom Checklist (SCL-90-R). Moreover, body height, weight, Body Mass Index (BMI) and the presence of amenorrhea were assessed. Regarding physical aspects, the rhythmic gymnasts showed an intermediate position between the two other groups. In terms of psychopathology, significant differences were found between the gymnasts and the AN patients, while no differences were detected between the gymnasts and the "normal" control group. Depression discriminated best between the three groups. Elite rhythmic gymnasts may show a lean, almost anorexic-like physique. Nevertheless, no psychological distress comparable to that of AN patients was found. Therefore, even though analogies to AN might seem obvious in elite rhythmic gymnasts, this study is putting emphasis on the importance of a careful consideration of psychological distress and psychopathology. PMID- 17846816 TI - The co-occurrence between internalizing and externalizing behaviors. A general population twin study. AB - Although Internalized and Externalized problem behaviors are described as separate phenomena at the psychometric and clinical levels, they frequently co occur. Only few studies, however, have investigated the causes of such covariation. In a sample of 398 twin pairs aged 8-17 drawn from the general population-based Italian Twin Registry, we applied bivariate genetic analyses to parent-rated CBCL/6-18 Internalization and Externalization scores. Covariation of Internalizing and Externalizing problem behaviors was best explained by genetic and common environmental factors, while the influence of unique environmental factors upon covariance appeared negligible. Odds ratio values showed that a borderline/clinical level of Externalization is a robust predictor of co-existing Internalizing problems in the same child, or within a sibship. Our findings help to approximate individual risks (e.g., in clinical practice, predicting the presence of Internalization in an externalizing child, and vice-versa), and to recognize that several shared environmental and genetic factors can simultaneously affect a child's proneness to suffer from both types of problem behaviors. PMID- 17846817 TI - Emotional and behavioural problems in migrant adolescents in Belgium. AB - Refugee and migrant adolescents may be at increased risk for the development of emotional and behavioural problems. Since studies on this topic are rather scarce and results inconsistent, this large-scale screening study aims at investigating the prevalence of emotional and behavioural problems in recently arrived migrant adolescents in Belgium, compared to Belgian peers. About 1,249 migrant adolescents and 602 Belgian adolescents filled in four self-report questionnaires on the prevalence of emotional and behavioural problems, traumatic experiences and symptoms of post-traumatic stress. Migrant adolescents experienced more traumatic events than their Belgian peers, and show higher levels of peer problems and avoidance symptoms. On the contrary, non-migrant adolescents reveal more symptoms of anxiety, externalizing problems and hyperactivity. Factors influencing the prevalence of emotional and behavioural problems are the number of traumatic events experienced, gender and the living situation. Although migrant and non-migrant adolescents don't differ much in the prevalence of emotional and behavioural symptoms, attention should be given to the screening and support of risk groups within the population of migrant adolescents, such as girls, those who experienced a lot of traumatic events and unaccompanied refugee children and adolescents. PMID- 17846818 TI - Differences between prepubertal- versus adolescent- onset bipolar disorder in a Spanish clinical sample. AB - OBJECTIVE: To examine patients attended and diagnosed with bipolar disorder (BD) at a child and adolescent psychiatry service; to record age of diagnosis and age of onset, and to study clinical differences between prepubertal and adolescent onset groups. METHODS: All patients currently attended for BD type I, type II or non specified BD were reviewed and divided into two age groups: prepubertal onset (beginning before age 13) and adolescent onset (beginning at or above age 13). RESULTS: The sample were 43 patients with BD. Fourteen (32.6%) with prepubertal onset and 29 (67.4%) with adolescent onset. Time between onset of symptoms and diagnosis was longer in the prepubertal onset group (1.2 years versus 0.8 years respectively, P = .05). Patients with prepubertal onset BD more frequently presented previous symptoms such as irritability and conduct problems and had a higher rate of comorbidity (more frequently attention-deficit/hyperactivity disorder-ADHD). The adolescent onset group more often presented psychotic symptoms. CONCLUSION: The clinical characteristics of patients with bipolar disorder differ according to whether onset is prepubertal or adolescent. PMID- 17846819 TI - Exploring variation in the d(N)/d(S) ratio among sites and lineages using mutational mappings: applications to the influenza virus. AB - We use a likelihood-based method for mapping mutations on a phylogeny in a way that allows for both site-specific and lineage-specific variation in selection intensity. The method accounts for many of the potential sources of bias encountered in mapping of mutations on trees while still being computationally efficient. We apply the method to a previously published influenza data set to investigate hypotheses about changes in selection intensity in influenza strains. Influenza virus is sometimes propagated in chicken cells for several generations before sequencing, a process that has been hypothesized to induce mutations adapting the virus to the lab medium. Our analysis suggests that there are approximately twice as many replacement substitutions in lineages propagated in chicken eggs as in lineages that are not. Previous studies have attempted to predict which viral strains future epidemics may arise from using inferences regarding positive selection. The assumption is that future epidemics are more likely to arise from the strains in which positive selection on the so-called "trunk lineages" of the evolutionary tree is most pervasive. However, we find no difference in the strength of selection in the trunk lineages versus other evolutionary lineages. Our results suggest that it may be more difficult to use inferences regarding the strength of selection on mutations to make predictions regarding viral epidemics than previously thought. PMID- 17846821 TI - Individual and mixture effects of selected pharmaceuticals and personal care products on the marine phytoplankton species Dunaliella tertiolecta. AB - Pharmaceuticals and personal care products (PPCPs) entering the environment may have detrimental effects on aquatic organisms. Simvastatin, clofibric acid, diclofenac, carbamazepine, fluoxetine, and triclosan represent some of the most commonly used and/or detected PPCPs in aquatic environments. This study analyzed the individual and mixture toxicity of these six PPCPs to the marine phytoplankton species Dunaliella tertiolecta using a standard 96-hour static algal bioassay protocol. All PPCPs tested had a significant effect on D. tertiolecta population cell density. However, of the six PPCPs tested, only triclosan yielded toxicity at typical environmental concentrations. The 96-hour EC(50) values for triclosan, fluoxetine, simvastatin, diclofenac, and clofibric acid were 3.55 microg/L, 169.81 microg/L, 22,800 microg/L, 185,690 microg/L, and 224,180 microg/L, respectively. An EC(50) value could not be determined for carbamazepine; however, the highest concentration tested (80,000 microg/L) reduced cell density by 42%. Both mixtures tested-simvastatin-clofibric acid and fluoxetine-triclosan-demonstrated additive toxicity. The presence of PPCP mixtures may decrease the toxicity threshold for phytoplankton populations. Detrimental effects on phytoplankton populations could ultimately impact nutrient cycling and food availability to higher trophic levels. The results of this study are a first step toward identifying the risk of PPCPs to estuarine organisms and may benefit environmental resource managers. PMID- 17846820 TI - Two paralogous genes encoding small subunits of ADP-glucose pyrophosphorylase in maize, Bt2 and L2, replace the single alternatively spliced gene found in other cereal species. AB - Two types of gene encoding small subunits (SSU) of ADP-glucose pyrophosphorylase, a starch-biosynthetic enzyme, have been found in cereals and other grasses. One of these genes encodes two SSU proteins. These are targeted to different subcellular compartments and expressed in different organs of the plant: the endosperm cytosol and the leaf plastids. The SSU gene encoding two proteins evolved from an ancestral gene encoding a single protein by the acquisition of an alternative first exon. Prior to the work reported here, this type of SSU gene had been found in all grasses examined except maize. In maize, two separate genes, Bt2 and L2, were known to have the same roles as the alternatively spliced gene found in other grasses. The evolutionary origin of these maize genes and their relationship to the SSU genes in other grasses were unclear. Here we show that Bt2 and L2 are paralogous genes that arose as a result of the tetraploidization of the maize genome. Both genes derive from an ancestral alternatively spliced SSU gene orthologous to that found in other grasses. Following duplication, the Bt2 and L2 genes diverged in function. Each took a different one of the two functions of the ancestral gene. Now Bt2 encodes the endosperm cytosolic SSU but does not contribute significantly to leaf AGPase activity. Similarly, L2 has lost the use of one of its two alternative first exons. It can no longer contribute to the endosperm cytosolic SSU but is probably responsible for the bulk of the leaf AGPase SSU. PMID- 17846822 TI - Percutaneous transluminal coronary angioplasty for coronary arterial stenosis in a 10-year-old boy with Kawasaki disease and a brief review. AB - A 10-year-old boy developed coronary artery stenosis 9 years after suffering Kawasaki disease with coronary artery aneurysms at the age of 7 months old. Percutaneous transluminal coronary angioplasty was performed successfully to dilate the coronary arteries in order to prevent obstruction of the coronary arteries. PMID- 17846823 TI - Neonatal right lung emphysema due to pulmonary artery sling. AB - Pulmonary artery sling is a rare variant of vascular ring where the left pulmonary artery arises from the right and loops behind the trachea or right bronchus causing airway compression. A 40-day-old infant had been mechanically ventilated since birth for severe hypercapnia and right lung emphysema. Left pulmonary artery reimplantation was successfully performed. PMID- 17846824 TI - Acute pancreatitis: value and impact of CT severity index. AB - Acute pancreatitis is a disease with a broad spectrum of findings that varies in severity from mild interstitial or edematous pancreas to severe forms with significant local and systemic complications that are associated with a substantial degree of morbidity and mortality. Several scoring systems are used to assess the severity and predict the outcome and prognosis of acute pancreatitis. These include the Ranson, Acute Physiology And Chronic Health Evaluation II (APACHE II) and Glasgow scales. The CT severity index (CTSI) derived by Balthazar et al. has become widely used for description of CT findings in acute pancreatitis. The purpose of this project was to examine the current best evidence about regarding the effect of using a CTSI on patient outcome and its value in comparison with other widely used scoring systems. PMID- 17846825 TI - Evidence-based practice in radiology: what color is your parachute? AB - Increasingly, constructive thought is being given to non-interpretive competencies in Radiology training and practice. Two of these are "Practice-Based Learning" and "Systems-Based Practice". These areas are evolving. It seems likely that, in some way, the paradigm of "Evidence-Based Practice" (EBP) derived from the McMaster/Centre for Evidence-Based Medicine (CEBM) methodology will form part of these new disciplines. This introductory article sets the scene for this Feature Section in Abdominal Imaging consisting entirely of short "Critically Appraised Topics" produced using EBP techniques. It is hoped that this will stimulate further discussion and consideration of the potential role of EBP in radiology education. PMID- 17846827 TI - Strategic environmental assessment of greenhouse gas mitigation options in the Canadian agricultural sector. AB - This article presents a methodological framework for strategic environmental assessment (SEA) application. The overall objective is to demonstrate SEA as a systematic and structured policy, plan, and program (PPP) decision support tool. In order to accomplish this objective, a stakeholder-based SEA application to greenhouse gas (GHG) mitigation policy options in Canadian agriculture is presented. Using a mail-out impact assessment exercise, agricultural producers and nonproducers from across the Canadian prairie region were asked to evaluate five competing GHG mitigation options against 13 valued environmental components (VECs). Data were analyzed using multi-criteria and exploratory analytical techniques. The results suggest considerable variation in perceived impacts and GHG mitigation policy preferences, suggesting that a blanket policy approach to GHG mitigation will create gainers and losers based on soil type and associate cropping and on-farm management practices. It is possible to identify a series of regional greenhouse gas mitigation programs that are robust, socially meaningful, and operationally relevant to both agricultural producers and policy decision makers. The assessment demonstrates the ability of SEA to address, in an operational sense, environmental problems that are characterized by conflicting interests and competing objectives and alternatives. A structured and systematic SEA methodology provides the necessary decision support framework for the consideration of impacts, and allows for PPPs to be assessed based on a much broader set of properties, objectives, criteria, and constraints whereas maintaining rigor and accountability in the assessment process. PMID- 17846828 TI - Simplification of pine forests due to utilization by Tibetan villages in southwest China. AB - In China, many rural communities depend upon forests to provide wood, fuel, fertilizer, animal bedding, and valuable non-timber forest products (NTFP). However, the degree to which forest resource extraction is compatible with new conservation aims is unclear because there is little information on the specific ecological effects of traditional forest collecting practices. Therefore, we compared the structure and floristics of Pinus densata forests exposed to three levels of resource extraction by Tibetan villages in northwest Yunnan: (1) a forest site protected from wood and timber removal, (2) moderately utilized forest sites exposed to traditional collecting practices, and (3) patches of highly utilized forest from which timber extraction is high in response to recent development pressures. The results show that understorey and cryptogamic species are reduced in all the utilized forest sites by comparison with the protected forest. However, the moderately utilized pine forests still provide good NTFP habitats by maintaining relatively high canopy covers, litter covers, and understorey structural complexity; this suggests that traditional forest resource use, while simplifying the forest, does not pose an increasing threat to pine forest integrity. By comparison, the highly utilized forests are transformed into open, herb-rich environments in which canopy covers and understorey complexity are depleted, and NTFP habitats are degraded. In the future it may be practical to enhance biodiversity by proscribing forest resource collection, but the immediate priority is to monitor the sustainability of forest utilization using indicators such as understorey development, litter cover, and cryptogamic richness. PMID- 17846829 TI - Using soil and water conservation contests for extension: experiences from the Bolivian mountain valleys. AB - Soil and water conservation (SWC) contests among farmer groups were organized in five rural villages in the Bolivian mountain valleys. The contests were aimed at quickly achieving widespread sustainable results. This article analyzes the effectiveness of these contests as an extension tool. Mixed results were obtained. In three villages, participation rates in the SWC activities introduced in the contests were still high even 2 years after project withdrawal. These were all villages where a solid foundation for sustainable development had been laid before the contests were held. Two years later, most families were still involved in maintenance of the SWC practices introduced in the contests, and many farmers had started to experiment with different soil management practices. However, replications of these SWC practices were not widespread, Conservation Leaders did not continue with their training activities, and the quality of maintenance of the practices was often not satisfactory. In order to become a more effective extension tool and achieve widespread impact, SWC contests must receive continued support by a catalyst agency. Moreover, other SWC contests should also be organized in which practices are not predefined. Given that SWC contests are a low-budget extension tool, local municipalities could become more actively involved. PMID- 17846830 TI - Forest value orientations in Australia: an application of computer content analysis. AB - This article explores the expression of three forest value orientations that emerged from an analysis of Australian news media discourse about the management of Australian native forests from August 1, 1997 through December 31, 2004. Computer-coded content analysis was used to measure and track the relative importance of commodity, ecological and moral/spiritual/aesthetic forest value orientations. The number of expressions of these forest value orientations followed major events in forest management and policy, with peaks corresponding to finalization of Regional Forest Agreements and conflicts over forest management. Over the time period analyzed, the relative share of commodity value orientation decreased and the shares of the ecological and moral/spiritual/aesthetic value orientations increased. The shifts in forest value orientations highlight the need for native forests to be managed for multiple values and the need for continued monitoring of forest values. PMID- 17846831 TI - Stakeholder perceptions of scientists: Lake Tahoe environmental policy from 1984 to 2001. AB - What factors explain stakeholders' perceptions of scientists in environmental politics? Questionnaire data are used to examine stakeholders' views of scientific experts in the context of Lake Tahoe environmental policy from 1984 to 2001. Stakeholders' perceptions of scientists have remained the same over time - despite a shift from adversarial to collaborative policymaking and after decades of mounting scientific evidence showing water quality declines. On average, stakeholders perceive scientists with limited influence on Lake Tahoe environmental policy and view them with mixed levels of skepticism. Stakeholders' evaluation of scientists is best explained by their beliefs about development versus the environment. Stakeholders in favor of more land development express distrust of scientists and negatively evaluate university researchers and consultants. Stakeholders in favor of environmental protection are more likely to trust scientists and positively evaluate university researchers and consultants. PMID- 17846832 TI - Alternative splicing in the dyslexia-associated gene KIAA0319. AB - The KIAA0319 gene in chromosome 6p22 has been strongly associated with developmental dyslexia. In this article we show a wide expression pattern of this gene in human adult brain by Northern blot analysis. We also performed RT-PCR analysis to detect alternative splicing variants in human brain. Most of the detected variants involve alternative splicing of the exons at the 5' and the 3' ends. Two main forms differing in the length of the 5' UTR are detected at approximately the same rate. Two variants (B and C) lacking exon 19, which encodes the transmembrane domain, are the main alternative forms detected among those predicted to encode protein. These two variants could be secreted and might be involved in signaling functions. A similar RT-PCR analysis performed in mouse and rat adult brains showed that only some of the alternative splicing variants are equivalent to those found in the human gene. PMID- 17846833 TI - An automatic correction method for the heel effect in digitized mammography images. AB - The most significant radiation field nonuniformity is the well-known Heel effect. This nonuniform beam effect has a negative influence on the results of computer aided diagnosis of mammograms, which is frequently used for early cancer detection. This paper presents a method to correct all pixels in the mammography image according to the excess or lack on radiation to which these have been submitted as a result of the this effect. The current simulation method calculates the intensities at all points of the image plane. In the simulated image, the percentage of radiation received by all the points takes the center of the field as reference. In the digitized mammography, the percentages of the optical density of all the pixels of the analyzed image are also calculated. The Heel effect causes a Gaussian distribution around the anode-cathode axis and a logarithmic distribution parallel to this axis. Those characteristic distributions are used to determine the center of the radiation field as well as the cathode-anode axis, allowing for the automatic determination of the correlation between these two sets of data. The measurements obtained with our proposed method differs on average by 2.49 mm in the direction perpendicular to the anode-cathode axis and 2.02 mm parallel to the anode-cathode axis of commercial equipment. The method eliminates around 94% of the Heel effect in the radiological image and the objects will reflect their x-ray absorption. To evaluate this method, experimental data was taken from known objects, but could also be done with clinical and digital images. PMID- 17846834 TI - Automatic multilevel medical image annotation and retrieval. AB - Image retrieval at the semantic level mostly depends on image annotation or image classification. Image annotation performance largely depends on three issues: (1) automatic image feature extraction; (2) a semantic image concept modeling; (3) algorithm for semantic image annotation. To address first issue, multilevel features are extracted to construct the feature vector, which represents the contents of the image. To address second issue, domain-dependent concept hierarchy is constructed for interpretation of image semantic concepts. To address third issue, automatic multilevel code generation is proposed for image classification and multilevel image annotation. We make use of the existing image annotation to address second and third issues. Our experiments on a specific domain of X-ray images have given encouraging results. PMID- 17846835 TI - Open source software projects of the caBIG In Vivo Imaging Workspace Software special interest group. AB - The Cancer Bioinformatics Grid (caBIG) program was created by the National Cancer Institute to facilitate sharing of IT infrastructure, data, and applications among the National Cancer Institute-sponsored cancer research centers. The program was launched in February 2004 and now links more than 50 cancer centers. In April 2005, the In Vivo Imaging Workspace was added to promote the use of imaging in cancer clinical trials. At the inaugural meeting, four special interest groups (SIGs) were established. The Software SIG was charged with identifying projects that focus on open-source software for image visualization and analysis. To date, two projects have been defined by the Software SIG. The eXtensible Imaging Platform project has produced a rapid application development environment that researchers may use to create targeted workflows customized for specific research projects. The Algorithm Validation Tools project will provide a set of tools and data structures that will be used to capture measurement information and associated needed to allow a gold standard to be defined for the given database against which change analysis algorithms can be tested. Through these and future efforts, the caBIG In Vivo Imaging Workspace Software SIG endeavors to advance imaging informatics and provide new open-source software tools to advance cancer research. PMID- 17846836 TI - Area extraction of the liver and hepatocellular carcinoma in CT scans. AB - In Korea, hepatocellular carcinoma is the third frequent cause of cancer death, occupying 17.2% among the whole deaths from cancer, and the rate of death from hepatocellular carcinoma comes to about 21 out of 100,000. This paper proposes an automatic method for the extraction of areas being suspicious as hepatocellular carcinoma from computed tomography (CT) scans and evaluates the availability as an auxiliary tool for the diagnosis of hepatocellular carcinoma. For detecting tumors in the internal of the liver from a CT scan, first, an area of the liver is extracted from about 45-50 CT slices obtained by scanning in 2.5-mm intervals starting from the lower part of the chest. In the extraction of an area of the liver, after the unconcerned areas outside of the bony thorax are removed, areas of the internal organs are segmented by using information on the intensity distribution of each organ, and an area of the liver is extracted among the segmented areas by using information on the position and morphology of the liver. Because hepatocellular carcinoma is a hypervascular tumor, the area corresponding to hepatocellular carcinoma appears more brightly than the surroundings in a CT scan, and also takes a spherical shape if the tumor shows expansile growth pattern. By using these features, areas being brighter than the surroundings and globe-shaped are segmented as candidate areas for hepatocellular carcinoma in the area of the liver, and then, areas appearing at the same position in successive CT slices among the candidates are discriminated as hepatocellular carcinoma. For the performance evaluation of the proposed method, experimental results obtained by applying the proposed method to CT scans were compared with the diagnoses by radiologists. The evaluation results showed that all areas of the liver and hypervascular tumors were extracted exactly and the proposed method has a high availability as an auxiliary diagnosis tool for the discrimination of liver tumors. PMID- 17846837 TI - Rectovaginal fistula in Crohn's disease. AB - PURPOSE: Crohn's disease is characterized by transmural bowel inflammation and a tendency to form fistulas with adjacent structures. Several different fistulas have been described: enterocutaneous, enteroenteric, enterovesical, enterovaginal, and perineal. Rectovaginal fistulas are difficult to treat despite multimodal therapy. This study was designed to review the current strategic options to best manage this condition. METHODS: We reviewed the English-language literature from 1966 to 2006, using PUBMED, targeting Crohn's disease involving vagina using key words "rectovaginal fistula and CD," "anovaginal fistula and CD," "anovaginal fistula," and "rectovaginal fistula." We excluded the involvement of the vagina from a pouch after a proctectomy. A total of 776 articles were found; 206 articles were identified and judged as being relevant on the basis of title-related articles and links were reviewed. Fifty-three articles were selected after reading the abstract or full manuscript. RESULTS: The management of rectovaginal fistula, representing 9 percent of all fistulas, remains a challenge in the setting of Crohn's disease. Medical treatments are not favorable with low rates of long-term symptomatic control and unacceptable high rates of recurrence. Several novel and new surgical techniques have been described, and rectal advancement flap, in selected patients, seems to have the most successful results. CONCLUSIONS: The management of rectovaginal fistula of Crohn's origin should involve both gastroenterologists and coloproctologists, with the best surgical results being achieved in patients receiving optimum medical therapy. More focused studies targeting these patients with the use of combined medical and surgical therapy are necessary. PMID- 17846838 TI - Death resulting from fournier gangrene secondary to thrombosis of very large hemorrhoids: report of a case. AB - A 53-year-old male was admitted with a two-day history of abdominal pain, anal bleeding, fever, diarrhea, vomiting, and mental confusion. A diagnosis of thrombosis of very large hemorrhoids (Grade 4) was made. On the day of admission, he underwent an exploring laparotomy followed by abdominoperineal resection. The peritoneal cavity was filled with pus and blood clots. Because rectal necrosis was involved, sigmoid colostomy was imperative. Twenty-eight hours after surgery, the patient demonstrated signs of soft-tissue perineal necrosis associated with progressive pain and fever. He developed a rapidly progressive gangrene of the lower limbs and scrotum followed by acute renal and respiratory failure, and he died of sepsis. At autopsy, the cadaver showed jaundice and a large gangrene of the perineum and lower limbs. The internal organs showed features secondary to sepsis complications. To the best of our knowledge, this is the first autopsy study of a patient who died because of complications of hemorrhoids. PMID- 17846839 TI - Clinical entity and treatment strategies for adult intussusceptions: 20 years' experience. AB - PURPOSE: Intestinal intussusception in adults is rare and the optimal management of this problem remains controversial. The purpose of this study was to determine the causes of intussusceptions in adults and to assess their treatment. METHODS: A retrospective review of patients older than aged 18 years who were diagnosed with intestinal intussusception at Tri-Service General Hospital between July 1984 and July 2004 was conducted. RESULTS: During the 20-year period, there were 292 patients with intussusception, 24 (8.2 percent) of which were adults. Abdominal pain was the most common presenting complaint (79.2 percent). The diagnosis of adult intussusception was made preoperatively in 18 cases (75 percent) and intraoperatively in 6 cases (25 percent). Of the 24 patients, 20 (83.3 percent) had a defined lesion; 11 (55 percent) lesions were benign and 9 (45 percent) were malignant. In eight patients (33.3 percent), the intussusception was reduced; perforation occurred in one patient (12.5 percent). Segmental resections were performed on 14 patients (58.3 percent), right hemicolectomies on 6 patients (25 percent), laparoscopic low anterior resection on 1 patient (4.2 percent), appendectomy on 1 patient (4.2 percent), and diverticulectomy on 1 patient (4.2 percent). Intraoperative colonoscopy was performed on three patients (12.5 percent) before reduction (lipomas were noted in 2 of the patients (66.7 percent) with limited resection of the ileum and preservation of the antireflux ileocecal valve. There was one perioperative mortality (4.2 percent) and seven postoperative morbidities (29.2 percent). CONCLUSIONS: Adult intussusception is an unusual and challenging condition and is a preoperative diagnostic problem. We discuss our 20 years of experience in treatment strategies for dealing with such unusual problems. PMID- 17846840 TI - Hereditary nonpolyposis colorectal cancer (Lynch Syndrome) in Argentina: report from a referral hospital register. AB - PURPOSE: The first Argentine experience with epidemiologic, molecular, and genetic counseling data is reported. METHODS: We analyzed 43 families fulfilling Amsterdam criteria identified from a prospective database with data from 779 relatives. RESULTS: Eleven families (25.6 percent) presented as Lynch I, 29 (67.4 percent) as Lynch II, and 3 (7 percent) as Muir-Torre syndrome. Among the 306 affected members, 197 cases of colorectal cancer were identified (mean age at diagnosis, 52.1 (range, 21-90) years). The most frequent extracolonic tumors were gastric adenocarcinoma in males and endometrium adenocarcinoma in females. A high incidence of breast cancer was observed (16 cases among 155 females, crude rate: 11,594.20/100,000). Twenty-seven patients (8.8 percent) developed more than one tumor. These patients were younger than those with only one tumor (45 vs. 51 years; P = 0.001). In 5 of 11 patients who underwent molecular sequencing, a pathologic mutation was found. A novel C deletion at 1910 nucleotide, codon 637, exon 12 of MSH2 gene was identified in a family with a strong aggregation of breast cancer with lack of MSH2 immunohistochemical staining. For 78.2 percent of counseled individuals, this session represented the first time they received information, and 73.9 percent stated that their physicians were unaware of their family background. CONCLUSIONS: Argentine families presented a high incidence of stomach cancer. The elevated incidence of breast cancer and its association with a novel hMSH2 mutation bring to consideration the inclusion of this malignancy as part of the syndrome. A lack of awareness by both physicians and persons at risk was observed. PMID- 17846841 TI - Mucinous rectal adenocarcinoma can be associated to tumor downstaging after preoperative chemoradiotherapy. AB - PURPOSE: The aim of this study was to evaluate downstaging as primary end point, and progression-free survival and overall survival as secondary end points, in rectal adenocarcinoma patients treated with preoperative chemoradiation. METHODS: One hundred and thirty-six extraperitoneal adenocarcinoma patients (33 low rectum T2, 74 T3, 29 T4 [without sacral invasion], 25 with mucinous subtype) were treated with posterior pelvis preoperative radiotherapy (5040 cGy total dose, 180 cGy/fr, 5 fr/w, 10-15 MV linac X-rays) and concomitant 5-fluorouracil-based chemotherapy. After 6 to 8 weeks patients underwent surgery and prechemoradiation clinical stage was compared with pathologic stage to evaluate downstaging in each patient. Seventy-four patients received adjuvant chemotherapy. Median follow-up was 39 months (4-84). RESULTS: Forty-four patients had macroscopic complete response, 52 patients had partial response, 37 patients showed no change and 3 patients had progression. At multivariate analysis only histotype showed correlation with downstaging (hazard ratio = 0.350 and 0.138 - 0.885 95 percent confidence interval) because of the evidence for poor downstaging in mucinous subtype. There were no significant differences in overall survival and progression-free survival between adenocarcinoma and mucinous subtype. CONCLUSIONS: The main finding is that mucinous histology is associated with poor downstaging after preoperative chemoradiation but this poor response was not associated with worse outcome in this small study. The good outcome for mucinous histology is at odds with other reports in the literature and requires further study. PMID- 17846842 TI - Laboratory bioassays of vegetable oils as kairomonal phagostimulants for grasshoppers (Orthoptera: Acrididae). AB - Vegetable oils have kairomonal attractant properties to grasshoppers primarily due to the presence of linoleic and linolenic fatty acids. These fatty acids are dietary essentials for grasshoppers and, once volatilized, can be detected by the insects' olfactory receptors. A laboratory bioassay method has been developed to identify vegetable oils that have fatty acid profiles similar to grasshoppers and that induce grasshopper attraction and feeding. Such oils could be useful kairomonal adjuvants and/or carriers for acridicide formulations. Three sets of laboratory bioassays demonstrated that the addition of a standard aliquot of different vegetable oils resulted in varying degrees of grasshopper feeding on otherwise neutral substrates. Addition of olive oil stimulated the greatest feeding in all three sets of assays, regardless of the age of the tested insects. Furthermore, addition of canola or flax oils markedly enhanced grasshopper feeding. These three oils--i.e., olive, canola, and flax oil--proved to be the best performing grasshopper stimulants. A second group of oils included rapeseed flax mix and rapeseed oils; however, their performance was not as consistent as oils in the first group--especially with regard to nymphal feeding. A third group of oils consisted of soybean, corn, peanut, and sunflower oil. Theoretical expectations regarding these oils varied wildly, suggesting that the results of a single bioassay should be cautiously interpreted as being negative. PMID- 17846843 TI - Hepatitis B virus infection predicts extrahepatic metastasis after hepatic resection in patients with large hepatocellular carcinoma. AB - BACKGROUND: Although extrahepatic metastasis occurs rarely after hepatic resection for hepatocellular carcinoma (HCC), the prognosis of these patients is extremely poor. Predictors of extrahepatic metastasis have not been fully investigated. METHODS: To identify predictors of extrahepatic metastasis after resection, we retrospectively investigated 77 patients with HCC tumors > 50 mm in diameter who underwent hepatic resection. We investigated correlations between postoperative extrahepatic metastasis and clinicopathologic factors as well as extrahepatic metastasis-free survival rate by log rank test and predictors of extrahepatic metastasis by univariate and multivariate logistic regression models. RESULTS: Hepatitis B surface antigen (HBs-Ag) was found in 25 (32.5%) of 77 patients, and extrahepatic metastasis occurred in 26 (33.8%). Patients with extrahepatic metastasis showed better liver function and a high occurrence of HBs Ag positivity than those without. The 5-year extrahepatic metastasis-free survival rate was worse in patients with HBs-Ag positivity, larger tumors (> or = 70 mm), higher alfa-fetoprotein level (> or = 300 ng/mL), and lower indocyanine green retention rate at 15 minutes (ICGR15) (< 15%) than in those without. By univariate logistic regression analysis, HBs-Ag positivity, larger HCC tumor (> or = 70 mm), lower ICGR15 (< 15%), and lower preoperative lymphocyte count (< 1000/mm3) were predictors of extrahepatic metastasis (P < .1). By multivariate analysis, HBs-Ag positivity was an independent predictor of postoperative extrahepatic metastasis (P = .04). CONCLUSIONS: In patients positive for HBs-Ag, radiologic examination of extrahepatic organs should be performed as a part of the postoperative surveillance. Hepatitis B virus infection may promote establishment of extrahepatic metastasis. PMID- 17846844 TI - The green flash. PMID- 17846845 TI - An uncommon cause of bilateral pulmonary nodules in a long-term smoker. AB - BACKGROUND: Dyspnea caused by pulmonary disease is a common symptom encountered by internists. The most likely diagnosis of pulmonary nodules in a long-term smoker is lung cancer. PATIENT/PARTICIPANT: We report a case of an elderly male with a 70-pack-year smoking history, presenting with exertional dyspnea for 6 months. INTERVENTIONS: Detailed review of history was negative. Examination was normal except for diminished breath sounds in all lung fields. Chest x-ray showed bilateral nodular opacities. Computed tomography of thorax revealed multiple bilateral lung masses. A whole-body positron emission tomography revealed enhancement only of the pulmonary masses. Bronchoalveolar lavage was negative for acid fast bacilli, nocardia, and fungi. MAIN RESULTS: Lung biopsy showed findings consistent with amyloidosis. Bone marrow biopsy done to investigate primary amyloidosis showed no clonal plasma cells or amyloid staining, thus suggesting a diagnosis of localized pulmonary amyloidosis. Patient is being managed conservatively with close follow-up for signs of progression. PMID- 17846846 TI - Understanding patient preference for integrative medical care: results from patient focus groups. AB - BACKGROUND: Integrative medicine (IM), a combination of conventional and complementary and alternative medicine (CAM), has become a popular source of medical care, yet little is known about its use. OBJECTIVE: To identify the motivations of people who choose IM for their primary care needs. DESIGN: Qualitative study from focus group data of regular users of IM. PARTICIPANTS: Six focus groups that include a total of 37 regular users of IM who consented to participate in a study of IM use. APPROACH: Focus group meetings were audiotaped and transcribed verbatim. Qualitative analysis using grounded theory was used to derive the motivations for use of IM. RESULTS: Participants beliefs include the following: the combination of CAM and conventional medicine is better than either alone; health is a combination of physical, emotional, and spiritual well being; nutrition and lifestyle play a role in wellness; and pharmaceuticals should be avoided except as a last resort. Participants suffer from health problems that are not well treated by conventional medicine. Participants want to discuss CAM with physicians and obtain guidance on its use. Participants want time with their providers, to feel listened to and to have the opportunity for shared decision making. CONCLUSION: Much of what patients are seeking in integrative medical care is likely universally shared: a strong therapeutic relationship with providers who listen and provide time and knowledgeable advice. Users believe a combined approach of CAM and conventional medicine is better than either alone and want to be able to discuss CAM use with their providers. PMID- 17846847 TI - Not your typical pneumonia: a case of exogenous lipoid pneumonia. AB - The constellation of chronic cough, dyspnea, and hemoptysis can include a broad range of differential diagnoses. Although uncommon, exogenous lipoid pneumonia (ELP) should be considered when patients present with this symptom complex. We report a case of a 72-year-old female who presented with hemoptysis, cough, and dyspnea. The admission computed tomography scan of the chest revealed progressive interstitial infiltrates. Bronchoscopy revealed diffuse erythema without bleeding. Culture and cytology of lavage fluid were negative. Open-lung biopsy revealed numerous lipid-laden macrophages and multinucleated foreign-body giant cells. On further questioning, the patient admitted to the daily use of mineral oil for constipation. The diagnosis of ELP was made. The literature review revealed that many cases typically present with chronic cough with or without dyspnea. Our case illustrates an unusual presenting symptom of hemoptysis and the need to identify patients who can be at risk of developing this rare condition. PMID- 17846848 TI - Incidence of finding residual disease for incidental gallbladder carcinoma: implications for re-resection. AB - Re-resection for gallbladder carcinoma incidentally discovered after cholecystectomy is routinely advocated. However, the incidence of finding additional disease at the time of re-resection remains poorly defined. Between 1984 and 2006, 115 patients underwent re-resection at six major hepatobiliary centers for gallbladder carcinoma incidentally discovered during cholecystectomy. Data on clinicopathologic factors, operative details, TNM tumor stage, and outcome were collected and analyzed. Data on the incidence and location of residual/additional carcinoma discovered at the time of re-resection were also recorded. On pathologic analysis, T stage was T1 7.8%, T2 67.0%, and T3 25.2%. The median time from cholecystectomy to re-resection was 52 days. At the time of re-resection, hepatic surgery most often consisted of formal segmentectomy (64.9%). Patients underwent lymphadenectomy (LND) (50.5%) or LND + common bile duct resection (43.3%). The median number of lymph nodes harvested was 3 and did not differ between LND alone (n = 3) vs LND + common duct resection (n = 3) (P = 0.35). Pathology from the re-resection specimen noted residual/additional disease in 46.4% of patients. Of those patients staged as T1, T2, or T3, 0, 10.4, and 36.4%, respectively, had residual disease within the liver (P = 0.01). T stage was also associated with the risk of metastasis to locoregional lymph nodes (lymph node metastasis: T1 12.5%; T2 31.3%, T3 45.5%; P = 0.04). Cystic duct margin status predicted residual disease in the common bile duct (negative cystic duct, 4.3% vs positive cystic duct, 42.1%) (P = 0.01). Aggressive re-resection for incidental gallbladder carcinoma is warranted as the majority of patients have residual disease. Although common duct resection does not yield a greater lymph node count, it should be performed at the time of re-resection for patients with positive cystic duct margins because over one-third will have residual disease in the common bile duct. PMID- 17846849 TI - Isolated periportal tuberculosis: characteristic findings of clinical imaging. AB - Isolated periportal tuberculous lymphadenopathy is a rare clinical entity. This report describes a 56-year-old woman with the disease, who showed characteristic findings on clinical imaging studies. Computed tomography showed a low-density mass with peripheral enhancement and calcification, adjacent to the pancreatic head and caudate lobe of the liver. 2-[Fluorine 18]fluoro-2-deoxy-D-glucose positron emission tomography imaging co-registered with computed tomography showed slightly increased uptake along the periphery of the lesion. The diagnosis was confirmed at laparotomy. The manifestation of the disease is nonspecific, and preoperative differential diagnosis from neoplastic disease is often difficult. Its clinical and radiological features are briefly reviewed. PMID- 17846851 TI - Early ERCP for gallstone pancreatitis: for whom and when? AB - The indications for early endoscopic retrograde cholangiopancreatography (ERCP) in gallstone pancreatitis are unclear, and the examination is often requested or performed without substantial supporting evidence. Several trials have been performed to determine the benefit of early ERCP in pancreatitis, yet the results of these studies are inconsistent. To more closely analyze these studies, we performed an evidence-based review of the outcomes of early ERCP in gallstone pancreatitis. To obtain the best available evidence, a PubMed search using the MeSH terms "gallstones" and "pancreatitis" was performed and further refined to identify appropriate studies. We included five randomized trials, a meta analysis, and a Cochrane Database Systematic Review in our detailed examination of the pertinent literature. Collectively, these studies suggest that early ERCP does not alter mortality in gallstone pancreatitis. In addition, few patients with mild pancreatitis benefit from the procedure, whereas some studies indicate that patients with severe pancreatitis or documented biliary obstruction may experience fewer complications if ERCP is performed. The data in the studies are confounding because of heterogeneity of the patient population and the inability to confirm gallstones in up to one third of patients. In conclusion, ERCP is not indicated for patients with mild pancreatitis. In select patients with severe disease or biliary obstruction, ERCP may be indicated. A multicenter trial designed to study the effect of early ERCP in severe pancreatitis only may provide additional useful information in patients with documented gallstones. PMID- 17846850 TI - Impact of changing epidemiology of gastroesophageal reflux disease on its diagnosis and treatment. AB - Gastroesophageal reflux disease (GERD) has emerged as one of the most common diseases in modern civilization. This article reviews selected changes in epidemiology of GERD during the past decade and provides information on treatment options with a focus on the impact of GERD and potential role of laparoscopic antireflux surgery in patients with diabetes mellitus, obesity, liver cirrhosis, at the extremes of life age and in immunocompromised individuals such as liver and lung transplant recipients. PMID- 17846852 TI - Laparoscopic vs open colectomy for colon cancer: results from a large nationwide population-based analysis. AB - PURPOSE: Laparoscopic colectomy has only recently become an accepted technique for the treatment of colon cancer. We sought to analyze factors that affect the type of resection performed and associated outcomes from a large nationwide database. METHODS: All admissions with a primary diagnosis of colon cancer undergoing elective resection were selected from the 2003 and 2004 Nationwide Inpatient Samples. Multiple linear and logistic regression analyses were used to compare outcome measures and identify independent predictors of a laparoscopic approach. RESULTS: We identified 98,923 admissions (mean age 69.2 years). They were predominately Caucasian (81%), had localized disease (63%), had private insurance (56%), and had surgery performed in urban hospitals (87%). Laparoscopic resection was performed in 3,296 cases (3.3%) and was associated with a lower complication rate (18% vs 22%), shorter length of stay (6 vs 7.6 days), decreased need for skilled aftercare (5% vs 11%), and lower mortality (0.6% vs 1.4%, all P<0.01). There was no significant difference in the total hospital charges between the groups ($34,685 vs $34,178, P=0.19). Independent predictors of undergoing laparoscopic resection were age<70 (odds ratio [OR]=1.2, P<0.01), national region (Midwest OR=1.9, West OR=2.0, P<0.01), and lower disease stage (OR=2.5, P<0.01). Ethnic category and insurance status showed no significant association with operative method (P>0.05). CONCLUSIONS: Laparoscopy for colon cancer is associated with improved outcomes in unadjusted analysis and similar charges compared to open resection. We found no influence of race or payer status on the utilization of a laparoscopic approach. PMID- 17846853 TI - A prospective, double-blind, multicenter, randomized trial comparing ertapenem 3 vs >or=5 days in community-acquired intraabdominal infection. AB - Severe secondary peritonitis is diagnosed in only 20-30% of all patients, but studies to date have persisted in using a standard fixed duration of antibiotic therapy. This prospective, double-blind, multicenter, randomized clinical study compared the clinical and bacteriological efficacy and tolerability of ertapenem (1 g/day) 3 days (group I) vs >or=5 days (group II) in 111 patients with localized peritonitis (appendicitis vs non-appendicitis) of mild to moderate severity, requiring surgical intervention. In evaluable patients, the clinical response as primary efficacy outcome were assessed at the test-of-cure 2 and 4 weeks after discontinuation of antibacterial therapy. Ninety patients were evaluable. In groups I and II, 92.9 and 89.6% of patients were cured, respectively; 95.3% in group I and 93.7% in group II showed eradication. These differences were not statistically significant. The most frequent bacteria recovered were Escherichia coli and Bacteroides fragilis. A wound infection developed in seven patients (7.7%) and an intraabdominal infection in one patient (1.1%). There was a low frequency of drug-related clinical or laboratory adverse effects in both groups. Our study demonstrated that, in patients with localized community-acquired intraabdominal infection, a 3-day course of ertapenem had the same clinical and bacteriological efficacy as a standard duration. PMID- 17846854 TI - Clinicopathologic features and treatment trends of pancreatic neuroendocrine tumors: analysis of 9,821 patients. AB - The natural history of pancreatic neuroendocrine tumors (PNET) remains poorly defined. Our objectives were to examine the clinicopathologic features of PNETs, to assess treatment trends over time, and to identify factors associated with undergoing resection. From the National Cancer Data Base (1985-2004), 9,821 patients were identified with PNETs. Clinicopathologic features and treatment trends were examined. Multivariable logistic regression was used to assess factors associated with undergoing resection. Of 9,821 patients with PNETs, 85% were nonfunctional, 7.1% were functional, and 7.9% were carcinoid tumors. Of the 3,851 (39.0%) patients who underwent pancreatectomy, 449 (11.7%) received adjuvant chemotherapy, and 254 (6.6%) received adjuvant radiation. From 1985 to 2004, utilization of pancreatectomy increased from 39.4 to 44.3% (P < 0.0001). Patients were less likely to undergo resection if they were > 55 years old, had tumors in the head of the pancreas, tumors > or = 4 cm, or had distant metastases (P < 0.0001). Patients treated at NCCN/NCI, academic, or high-volume hospitals were more likely to undergo resection. There are disparities in the utilization of pancreatectomy for PNETs. As PNETs have a better prognosis than adenocarcinoma, concerns regarding the morbidity and mortality of pancreatic surgery and neoplasms should not preclude resection. PMID- 17846856 TI - Salvage surgery after failed chemoradiation for anal canal cancer: should the paradigm be changed for high-risk tumors? AB - It is common belief that patients failing chemoradiation therapy (CRT) for squamous cell cancer of the anus (SCCA) can be salvaged with subsequent surgery. The aim of this study was to examine our experience with abdominoperineal resection (APR) in cases of persistent or recurrent SCCA with an emphasis on survival and morbidity. All patients between 1985 and 2001 undergoing salvage APR were reviewed. Details of CRT, surgery, tumor characteristics, postoperative complications, and survival were obtained from medical records. There were 22 patients (13 women, 9 men) with a mean age of 62 years (range=42-87). Initial tumors were AJCC stage 2 (16 cases), 3A (3 cases), and 4 (1 case). Mean radiation dose was 47.6 Gy (30-60) and most received concomitant 5-FU. In 20 patients, APR was felt to be "curative" but only 13 (65%) had negative margins on final pathology. Thirteen (59%) perineal wounds broke down with a median time to healing of 7 months. Tumor differentiation (p=0.02) and positive resection margins (p=0.004) were significantly associated with DFS (5-year DFS of 37%). Salvage APR in patients with poorly differentiated tumors or positive resection margins has a high morbidity and poor survival and may warrant a planned APR after CRT instead. PMID- 17846855 TI - Clarithromycin resistance, tumor necrosis factor alpha gene polymorphism and mucosal inflammation affect H. pylori eradication success. AB - Several bacterial and host-related factors concur in causing Helicobacter pylori eradication failure. We ascertained the role of bacterial virulence genes (cagA, vacA), clarithromycin resistance [Cla(R), 23S ribosomal RNA (rRNA) mutations], host polymorphism of CYP2C19 (polyphosphoinositide, PPI, metabolism) and of the cytokines IL-1B-31C>T, IL-1RN VNTR, IFN-gamma+874A>T, TNF-alpha-1031T>C, TNF alpha-857C>T, TNF-alpha-376G>A, TNF-alpha-308G>A, TNF-alpha-238G>A, IL-10 1082A>G, IL-10-819C>T, IL-10-592C>A, IL-12A+6686G>A, IL-12B+15485A>C. Two groups of H. pylori-infected and H. pylori-treated patients were retrospectively identified: 45 not eradicated and 57 eradicated. Treatment failure was significantly correlated with Cla(R) (all resistant strains in non-eradicated patients); with TNF-alpha-238, IL10-819, IL10-592, IL-12B+15485 single nucleotide polymorphism (SNP); with IL10 ATA/ATA haplotype; and with antral inflammatory grade. On considering Cla(S)-infected patients only, logistic regression analysis (eradication = dependent; TNF-alpha-238, IL12B + 15485 genotypes, IL10 ATA/ATA as present or absent, antral gastritis grade = covariates) confirmed as significantly correlated with eradication antral gastritis grade only (Exp(B) = 6.48; 95% CI, 1.2-35.01). In conclusion, the bacterial determinant causing triple therapy failure is clarithromycin resistant, being virulence genes not involved. The host related factors that favor eradication are those linked to inflammation: a higher inflammatory infiltrate in the mucosa, possibly favored by genotypes able to down regulate the anti-inflammatory cytokine response, enhance the chance of eradication success. PMID- 17846857 TI - Development and characterization of a continuous cell line, AFKM-On-H, from hemocytes of the European corn borer Ostrinia nubilalis (Hubner) (Lepidoptera, Pyralidae). AB - The corn borer, Ostrinia nubilalis, is a very important pest in different countries, and the in vitro system of the insect could be a useful tool for isolation and characterization of the pathogens and physiological responses of the insect. In this context, a cell line was derived from the hemocytes of the European corn borer and was named AFKM-On-H for, respectively, O. nubilalis, Armand Frappier, King Mongkut Institutes, and Hemocytes. This cell line was initiated and maintained in Ex-Cell 400 medium supplemented with 10% heat inactivated fetal bovine serum. The cells, mostly spherical in shape, not firmly attached to the plastic culture flasks, were passaged up to 200 times by repeated gentle pipetting of the cells. The doubling times at the 80th and 125th passages at 28 degrees C and at the 122th and 169th passages at 25 degrees C were 40, 29, 35, and 34 h, respectively. The AFKM-On-H cell line was further characterized by the morphology, karyotype, random amplified polymorphic DNA analysis, and isozyme profiles. Susceptibility of the cell line to cytoplasmic polyhedrosis viruses (CPV) Euxoa scandens (EsCPV), Dendrolimus punctatus (DpCPV), and Choristoneura fumiferana (CfCPV); nuclear polyhedrosis viruses [Autographa californica (AcMNPV) wild type and recombinant, Antherea yammamai (AnyaNPV)]; and Chilo iridescent virus was demonstrated. Relative sensitivities of the cell line to Bacillus thuringiensis and Metarhizium anisopliae toxins and effects of the molting hormone 20-hydroxyecdysone on this new hemocyte cell line were characterized. PMID- 17846858 TI - Immunohistochemical evidence that culture in the high aspect rotating vessel can up-regulate hormone expression in growth dedifferentiated PHHI-derived islet cells. AB - Islet cells derived from patients with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) have the ability to grow readily in simple culture media. However, as with primary islets and cell lines, they lose hormone expression upon growth. In this study, we have investigated the role of three-dimensional cell-to cell contact in the reinitiation of hormone expression in growth dedifferentiated PHHI-derived cells. Two main methods of cell aggregation were studied; the promotion of pseudoislets through petri dish culture and the creation of cell aggregates in the microgravity environment of the high aspect ratio vessel (HARV). Immunohistochemical analysis and ELISA assay showed that petri dish culture did not re-establish endocrine expression in any of the five cultures tested. However, through HARV technology, we have demonstrated that it is possible to reactivate insulin, glucagon, somatostatin, and GAD expression in PHHI-derived cells that had previously stopped expressing these markers. These results indicate that the unique environment of the HARV can be conducive to the upregulation of endocrine expression of islet-derived cells and optimization of culture conditions may prove useful in the sphere of beta cell proliferation. PMID- 17846859 TI - Bone turnover and bone collagen maturation in osteoporosis: effects of antiresorptive therapies. AB - Bone collagen maturation may be important for anti-fracture efficacy as the reduction in risk is only partly explained by a concomitant increase in BMD during anti-resorptive therapy. Different treatments caused diverse profiles in bone collagen degradation products, which may have implications for bone quality. INTRODUCTION: The aim of the present study was to evaluate the effect of different anti-resorptive treatments on bone collagen maturation measured as the ratio between the degradation products of newly synthesized and mature isomerized C-telopeptides of type I collagen. METHODS: Participants were from cohorts of healthy postmenopausal women participating in double blind, placebo-controlled 2 year studies of alendronate, ibandronate, intranasal hormone replacement therapy (HRT), oral HRT, transdermal HRT, or raloxifene (n = 427). The non-isomerized alphaalphaCTX and isomerized betabetaCTX were measured in urine samples obtained at baseline, and after 6, 12, and 24 months of therapy. RESULTS: Bone collagen maturation measured as the ratio between alphaalphaCTX and betabetaCTX showed that bisphosphonate treatment induced a collagen profile consistent with an older matrix with a 52% (alendronate) and 38% (ibandronate) reduction in the ratio between the two CTX isoforms vs. 3% and 15% with HRT or raloxifene, respectively. CONCLUSIONS: Anti-resorptive treatments had different effects on the endogenous profile of bone collagen maturation. Whether that effect on bone collagen has an impact on bone strength independent on the treatment-dependent effect on BMD should be investigated. PMID- 17846860 TI - Bone mineral density in post-menopausal female subjects is associated with serum antioxidant carotenoids. AB - High intake of fruit and vegetables may reduce the risk of osteoporosis. Carotenoids exist in abundance in these foods. This study showed the association of bone mineral density with serum carotenoids. The findings suggest that beta cryptoxanthin and beta-carotene might provide benefits to bone health in post menopausal female subjects. INTRODUCTION: Antioxidant carotenoids are abundant in fruit and vegetables. Recent epidemiological studies show that high intakes of fruit and vegetables may reduce the risk of osteoporosis, but little is known about the association of bone mineral density (BMD) with serum carotenoids. METHODS: A total of 699 subjects (222 males and 477 females) who had received health examinations in the town of Mikkabi, Shizuoka Prefecture, Japan, participated in the study. Radial BMD was measured using dual-energy X-ray absorptiometry (DXA). The associations of serum carotenoid concentrations with the radial BMD were evaluated cross-sectionally. RESULTS: In male and pre menopausal female subjects, the six serum carotenoids were not associated with the radial BMD. On the other hand, in post-menopausal female subjects, serum beta cryptoxanthin and beta-carotene were weakly but positively correlated with the radial BMD. After adjustment for confounders, the odds ratio (OR) for the lowest quartile of BMD in the high groups (Q2-Q4) of serum beta-cryptoxanthin against the lowest quartile (Q1) was 0.45 (95% confidence interval: 0.22-0.95) in post menopausal female subjects. However, this association was not significant after further adjusting for intakes of minerals and vitamins. CONCLUSIONS: Antioxidant carotenoids, especially beta-cryptoxanthin, significantly but partly associate with the radial BMD in post-menopausal female subjects. PMID- 17846861 TI - In vivo 3D reconstruction of human vertebrae with the three-dimensional X-ray absorptiometry (3D-XA) method. AB - We used a standard DXA device equipped with a C-arm to do in vivo reconstruction of human vertebrae from two orthogonal scans. This new technique, called 3D-XA (three-dimensional X-ray absorptiometry), allows the direct measurement of geometric parameters of the vertebrae with a good accuracy and precision. INTRODUCTION: Geometric parameters are predictors of bone strength. A technique called three-dimensional X-ray absorptiometry (3D-XA) allows 3D reconstruction of bones from DXA scans. We used the 3D-XA method to reconstruct human vertebrae and to evaluate the method's in vitro accuracy and in vivo precision. METHODS: A standard DXA device equipped with a C-arm was used. Calibration of its environment and identification of different anatomical landmarks of the vertebrae allows personalized 3D geometric reconstruction of vertebrae. Accuracy was calculated by reconstructing 16 dry human vertebrae by 3D-XA and CT scanner. In vivo inter-observer precision was calculated using 20 human spines. RESULTS: The mean difference between 3D reconstruction by CT and 3D-XA was -0.2 +/- 1.3 mm. The in vivo mean difference of the 3D-XA method between the two rheumatologists was -0.1 +/- 0.8 mm. For geometric parameters, mean difference ranged from 0.4 to 0.9 mm. For cross-sectional area and vertebral body volume, it was 2.9% and 3.2%, respectively. CONCLUSION: This study shows the good accuracy and precision of 3D XA using a standard DXA device. It yields complementary information on bone geometry. Further studies are needed to evaluate if, coupled with bone density, it improves vertebral fracture risk prediction. PMID- 17846862 TI - Siderotyping of fluorescent Pseudomonas: molecular mass determination by mass spectrometry as a powerful pyoverdine siderotyping method. AB - The numerous pyoverdines so far characterized as siderophores of fluorescent Pseudomonas could be usually differentiated one from each others by the two physico-chemical and physiological methods of siderotyping, i.e., siderophore isoelectrofocusing and siderophore-mediated iron uptake. As shown in the present paper, the structural diversity of the peptide chain characterizing these molecules results in a very large panel of molecular masses representing 64 different values ranging from 889 to 1,764 Da for the 68 compounds included in the study, with only a few structurally different compounds presenting an identical molecular mass. Thus, the molecular mass determination of pyoverdines through mass spectrometry could be used as a powerful siderotyping method. PMID- 17846863 TI - On the development of models in mice of advanced visceral metastatic disease for anti-cancer drug testing. AB - It is well known clinically that advanced, bulky visceral metastatic disease is generally much less responsive to most anti-cancer therapies, compared to microscopic metastatic disease. This problem is exacerbated when treating cancers that have been previously exposed to multiple lines of therapy, and which have acquired a 'refractory' phenotype. However, mimicking such clinical treatment situations in preclinical mouse models involving the testing of new or existing cancer therapies is extremely rare. Treatment of 'metastasis', in retrospect, usually involves minimal residual disease and therapy naive tumors. This could account in many instances for the failure to reproduce highly encouraging preclinical results in subsequent phase I or phase II clinical trials. To that end, we have embarked on an experimental program designed to develop models of advanced, visceral metastatic disease, in some cases involving tumors previously exposed to various therapies. The strategy first involves the orthotopic transplantation of a human cancer cell line, such as breast cancer cell line, into the mammary fat pads of immune deficient mice, followed by surgical resection of the resultant primary tumors that develops. Recovery of distant macroscopic metastases, usually in the lungs, is then undertaken, which can take up to 4 months to visibly form. Cell lines are established from such metastases and the process of orthotopic transplantation, surgical resection, and recovery of distant metastases is undertaken, at least one more time. Using such an approach highly metastatically aggressive variant sublines can be obtained, provided they are once again injected into an orthotopic site and the primary tumors removed by surgery. By waiting sufficient time after removal of the primary tumors, about only 1 month, mice with extensive metastatic disease in sites such as the lungs, liver, and lymph nodes can be obtained. An example of therapy being initiated in an advanced stage of such disease development is illustrated. Metastases that eventually stop responding to a particular therapy can be removed as a source of variant cell lines which have both 'refractory' and highly metastatic phenotypes. Such models may provide a more accurate picture of the potential responsiveness to an experimental therapy so that a high degree of responsiveness observed could be a factor in deciding whether to move a particular therapy forward into phase I/phase II clinical trial evaluation. An example of this is illustrated using doublet metronomic low-dose chemotherapy for the treatment of advanced metastatic breast cancer, using two conventional chemotherapy drugs, namely, cyclophosphamide and UFT, a 5-FU oral prodrug. PMID- 17846864 TI - Transformation products of extracellular NAD(+) in the rat liver: kinetics of formation and metabolic action. AB - The perfused rat liver responds in several ways to NAD(+) infusion (20-100 microM). Increases in portal perfusion pressure and glycogenolysis and transient inhibition of oxygen consumption and gluconeogenesis are some of the effects that were observed. Extracellular NAD(+) is also extensively transformed in the liver. The purpose of the present work was to determine the main products of extracellular NAD(+) transformation under various conditions and to investigate the possible contribution of these products for the metabolic effects of the parent compound. The experiments were done with the isolated perfused rat liver. The NAD(+) transformation was monitored by HPLC. Confirming previous findings, the single-pass transformation of 100 microM NAD(+) ranged between 75% at 1.5 min after starting infusion to 95% at 8 min. The most important products of single pass NAD(+) transformation appearing in the outflowing perfusate were nicotinamide, ADP-ribose, uric acid, and inosine. The relative proportions of these products presented some variations with the time after initiation of NAD(+) infusion and the perfusion conditions, but ADP-ribose was always more abundant than uric acid and inosine. Cyclic ADP-ribose (cADP-ribose) as well as adenosine were not detected in the outflowing perfusate. The metabolic effects of ADP ribose were essentially those already described for NAD(+). These effects were sensitive to suramin (P2(XY) purinergic receptor antagonist) and insensitive to 3,7-dimethyl-1-(2-propargyl)-xanthine (A2 purinergic receptor antagonist). Inosine, a known purinergic A3 agonist, was also active on metabolism, but uric acid and nicotinamide were inactive. It was concluded that the metabolic and hemodynamic effects of extracellular NAD(+) are caused mainly by interactions with purinergic receptors with a highly significant participation of its main transformation product ADP-ribose. PMID- 17846865 TI - Brain microvascular and intracranial artery resistance to atherosclerosis is associated with heme oxygenase and ferritin in Japanese quail. AB - Oxidative stress and increased oxidation of low-density lipoprotein (oxLDL) through free radical-mediated tissue injury may be important factors in the development of extracranial atherosclerotic lesions. However, the roles of oxidative stress and hypercholesterolemia in intracranial atherosclerosis is less established. The induction of heme oxygenase (HO) is a cellular response to oxidative stress, and inducible HO (HO-1) may protect against oxidized lipids such as those produced by oxidative stress. We investigated the effects of oxLDL on cell and tissue viability, HO-1 and ferritin expression in extracranial and intracranial endothelial cells, and the arteries of cholesterol-induced atherosclerosis (CIA) Japanese quail. We report that cultured microvascular endothelial cells from the brain (QBMEC) and carotid (QCEC) differ in their response to oxidative stress. The QCECs are less responsive than QBMECs to oxidative stress induced by oxLDL, as evident by lower expression of HO-1 mRNA, HO activity, and ferritin levels. Furthermore, the higher levels of catalytic iron, thiobarbituric acid reactive substances, and lactate dehydrogenase released in QCECs indicated that these cells are more susceptible to oxidative stress than QBMECs. We also investigated the relationship between extent of atherosclerotic plaque deposition and the extracranial and intracranial arterial expression of HO 1 in quail. The common carotid and vertebral (extracranial) arteries had higher tissue cholesterol levels (starting at 2 weeks of cholesterol-supplementation) and a greater atherosclerotic plaque score (starting at 4 weeks of cholesterol supplementation) compared with middle cerebral and basilar (intracranial) arteries, and this may be relevant to the effect of aging on the process of atherogenesis. The extracranial arteries also had early and greater levels of lipid peroxidation and catalytic iron coupled with lower expression of HO-1 protein, HO activity, and ferritin compared to the intracranial vessels. These observations suggest that the extracranial and intracranial arterial walls respond differently to oxidation of lipoproteins, and support the feasibility of increased HO-1 expression as a means of protection against oxidant injury. PMID- 17846866 TI - The N-terminal coiled-coil domain of the cytohesin/ARNO family of guanine nucleotide exchange factors interacts with Galphaq. AB - Cytohesins are guanine-nucleotide exchange factors (GEF) for the Arf family of GTPases. One member of the Arf family, ARF6, plays an active role in the intracellular trafficking of G protein-coupled receptors. We have previously reported that Galphaq signaling leads to the activation of ARF6, possibly through a direct interaction with cytohesin-2/ARNO. Here, we report that Galphaq can directly interact with cytohesin-1, another Arf-GEF of the ARNO/cytohesin family. Cytohesin-1 preferentially associated with a constitutively active mutant of Galphaq (Galphaq-Q209L) compared to wild-type Galphaq in HEK293 cells. Stimulation of TPbeta, a Galphaq-coupled receptor, to activate Galphaq resulted in the promotion of a protein complex between Galphaq and cytohesin-1. Confocal immunofluorescence microscopy revealed that wild-type Galphaq and cytohesin-1 co localized in intracellular compartments and at or near the plasma membrane. In contrast, expression of Galphaq-Q209L induced a drastic increase in the localization of cytohesin-1 at the plasma membrane. Expression of a dominant negative mutant of cytohesin-1 reduced by 40% the agonist-induced internalization of TPbeta, a process that we previously demonstrated to be dependent on Galphaq mediated signaling and Arf6 activation. Using deletion mutants, we show that cytohesin-1 interacts with Galphaq through its N-terminal coiled-coil domain. Cytohesin-1 and cytohesin-2/ARNO mutants lacking the coiled-coil domain were unable to relay Galphaq-mediated activation of Arf6. This is the first report of an interaction between the coiled-coil domain of the cytohesin/ARNO family of Arf GEFs and a member of the heterotrimeric G proteins. PMID- 17846867 TI - Mechanistic understanding of oral drug absorption enhancement of cromolyn sodium by an amino acid derivative. AB - PURPOSE: Examine the oral absorption enhancement mechanism of cromolyn sodium by sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) by evaluating the effect of SNAC on cromolyn sodium lipophilicity and changes in Caco-2 cell membrane fluidity. MATERIALS AND METHODS: Standard Shake-flask method was used to evaluate the effect of SNAC on the lipophilicity of cromolyn sodium. The measurements were carried out in three partitioning solvents with varying hydrogen-bonding properties. Steady state fluorescence emission anisotropy technique was used to evaluate the effect of SNAC with/without cromolyn sodium on Caco-2 cell membrane fluidity. RESULTS: The lipophilicity measurements showed that SNAC had no influence on the lipophilicity of cromolyn sodium in the three partitioning solvent systems. The findings of the steady-state fluorescence anisotropy showed that SNAC increases the membrane fluidity of the Caco-2 cells in a concentration dependent manner. The increase in fluidity with SNAC was seen in the presence and absence of cromolyn sodium and the presence of cromolyn sodium did not augment the effect of SNAC on membrane fluidity. CONCLUSIONS: The increase in membrane fluidity by SNAC plays a pivotal role in the permeation enhancement mechanism of cromolyn sodium. Therefore, the increase in permeation is a result of changing Caco-2 cell membrane fluidity resulting in change in membrane integrity and not due to an increase in the lipophilicity of cromolyn sodium through its interaction with SNAC. PMID- 17846868 TI - Membrane transporters in drug disposition. PMID- 17846870 TI - Recrystallization of nifedipine and felodipine from amorphous molecular level solid dispersions containing poly(vinylpyrrolidone) and sorbed water. AB - PURPOSE: To compare the physical stability of amorphous molecular level solid dispersions of nifedipine and felodipine, in the presence of poly(vinylpyrrolidone) (PVP) and small amounts of moisture. METHODS: Thin amorphous films of nifedipine and felodipine and amorphous molecular level solid dispersions with PVP were stored at various relative humidities (RH) and the nucleation rate was measured. The amount of water sorbed at each RH was measured using isothermal vapor sorption and glass transition temperatures (Tg) were determined using differential scanning calorimetry. The solubility of each compound in methyl pyrrolidone was measured as a function of water content. RESULTS: Nifedipine crystallizes more easily than felodipine at any given polymer concentration and in the presence of moisture. The glass transition temperatures of each compound, alone and in the presence of PVP, are statistically equivalent at any given water content. The nifedipine systems are significantly more hygroscopic than the corresponding felodipine systems. CONCLUSIONS: Variations in the physical stability of the two compounds could not be explained by differences in Tg. However, the relative physical stability is consistent with differences in the degree of supersaturation of each drug in the solid dispersion, treating the polymer and water as a co-solvent system for each drug compound. PMID- 17846871 TI - Exposure therapy for problem gambling via Videoconferencing: a case report. AB - This case report of a 31 year old woman who described her main problem as an uncontrollable urge to gamble on electronic gaming machines describes the application of exposure therapy (ET) by videoconferencing and the use of a clinical therapy assistant in the treatment of pathological gambling. The case study is used to demonstrate the effectiveness of this treatment with six sessions of therapy and 4 year follow up. The use of videoconferencing is discussed in relation to treatment effectiveness, ongoing follow up for the client and education and support for a community mental health nurse, therapy assistant, in a rural setting in South Australia. The implications of using this modality for the treatment of rural patients with problem gambling is discussed. PMID- 17846869 TI - Computational models to assign biopharmaceutics drug disposition classification from molecular structure. AB - PURPOSE: We applied in silico methods to automatically classify drugs according to the Biopharmaceutics Drug Disposition Classification System (BDDCS). MATERIALS AND METHODS: Models were developed using machine learning methods including recursive partitioning (RP), random forest (RF) and support vector machine (SVM) algorithms with ChemDraw, clogP, polar surface area, VolSurf and MolConnZ descriptors. The dataset consisted of 165 training and 56 test set molecules. RESULTS: RF model 3, RP model 1, and SVM model 1 can correctly predict 73.1, 63.6 and 78.6% test compounds in classes 1, 2 and 3, respectively. Both RP and SVM models can be used for class 4 prediction. The inclusion of consensus analysis resulted in improved test set predictions for class 2 and 4 drugs. CONCLUSIONS: The models can be used to predict BDDCS class for new compounds from molecular structure using readily available molecular descriptors and software, representing an area where in silico approaches could aid the pharmaceutical industry in speeding drugs to the patient and reducing costs. This could have significant applications in drug discovery to identify molecules that may have future developability issues. PMID- 17846872 TI - Pyrene-1-carboxylate in water and glycerol solutions: origin of the change of pK upon excitation. AB - Pyrene-1-carboxy acid has a pK of 4 in the ground state, and a pK of 8 in the excited state. Fluorescence spectra of the acid and base forms are presented as a function of solvent and temperature. Ab initio quantum calculations indicate that the bond between the ring system and the carboxyl group has aromatic character that becomes stronger upon excitation. This stabilization helps to account for the increase in pK upon excitation. PMID- 17846873 TI - Alteration of the expression of CD44 [corrected] isoforms in oral epithelia and saliva from patients with oral lichen planus. AB - Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that cell mediated immunological mechanisms are involved in pathogenesis. The objective of this study was to investigate the expression of CD44 isoforms including CD44s, CD44v5, and CD44v6 in biopsy specimens and saliva from OLP patients. Thirty-one OLP patients and 30 healthy subjects were enrolled in this study. Immunohistochemical methods were used to detect the expression of CD44 isoforms in oral epithelia, and enzyme-linked immunosorbent assay (ELISA) was performed to measure levels of salivary CD44 isoforms. Our results demonstrated that expression of CD44v6 in oral epithelia from OLP patients was significantly decreased in comparison to controls (p = 0.021). Levels of salivary CD44s and CD44v5 from OLP patients were significantly higher than those from controls (p = 0.007 and p = 0.002, respectively). In summary, our findings provided additional evidence that the pathological stress, such as chronic inflammation, altered the expression of CD44 isoforms in oral epithelia and saliva of OLP patients. PMID- 17846874 TI - Study of caprine beta-casein using reversed-phase high-performance liquid chromatography and mass spectroscopy: identification of a new genetic variant. AB - The genotypes and the main phosphorylation levels of beta-casein of goat milk were studied using RP-HPLC/ESI-MS. A new variant of caprine beta-casein named E has been characterized using RP-HPLC/ESI-MS, MALDI-MS and NanoESI MS/MS methods. Its sequence differed from that of variant A in the mono amino acid substitution D47 --> Y47, which resulted in a 48 Da experimental mass difference between them. The calculated molecular mass of the new variant E 6 P was estimated as 23,869 Da. Its phosphorylation pattern was similar to that of variant A, the most abundant types being those with 5 and 6 P in similar quantities. PMID- 17846875 TI - The treatment of hepatic encephalopathy. AB - Current recommendations for the treatment of hepatic encephalopathy are based, to a large extent, on open or uncontrolled trials, undertaken in very small numbers of patients. In consequence, there is ongoing discussion as to whether the classical approach to the treatment of this condition, which aims at reducing ammonia production and absorption using either non-absorbable disaccharides and/or antibiotics, should be revisited, modified or even abandoned. Pros and cons of present therapeutic strategies and possible future developments were discussed at the fourth International Hannover Conference on Hepatic Encephalopathy held in Dresden in June 2006. The content of this discussion is summarized. PMID- 17846876 TI - Myocardial stunning following defibrillation threshold testing. AB - Implantable cardioverter-defibrillators (ICDs) have a proven mortality benefit in appropriately selected people. Several retrospective studies, though, have postulated that appropriate ICD therapy may lead to fatal, pulseless electrical alternans (PEA). This case report describes an episode of transient PEA from myocardial stunning and standstill following defibrillation threshold testing. The risk of post-shock myocardial stunning and standstill should be kept in mind as a potential complication of testing. With rapid recognition and prompt intervention, this complication is potentially reversible. PMID- 17846877 TI - How older Vietnamese Australian women manage their medicines. AB - Safe use of medicines is relevant to all, but especially older people, primarily because they have ageing bodies that require more medicines and are therefore more likely to experience complications, including adverse drug interactions. Australia has a rapidly growing migrant older population composed of people with different beliefs about, and practices using, medicines. This paper presents qualitative findings from interviews and focus groups conducted with older Vietnamese-Australian women living in Sydney, Australia. The findings show how the women's health literacy influenced their medication use and explain the cultural reasons behind their decision to vary medicine use from that prescribed by their western trained doctors. Concern that health professionals do not favour combining western with traditional medicines led some participants to manage their medicines without advice from their doctor. The findings support recommendations to reduce the likelihood of adverse medication outcomes by increasing health professionals' cultural competence, encouraging patients to work with their doctor and report all medications taken, and increasing funding for research into the effects of combining western with traditional medicines. PMID- 17846878 TI - The influence of personality disorder indication, social support, and grief on alcohol and cocaine use among HIV-positive adults coping with AIDS-related bereavement. AB - Substance use is prevalent among HIV-positive adults and linked to a number of adverse health consequences; however little is known about risk and protective factors that influence substance use among HIV-positive adults coping with AIDS related bereavement. Using structural equation modeling (SEM), male gender, diagnostic indications of antisocial and borderline personality disorders (PD), and grief severity were tested as risk factors, and social support as a protective factor, for alcohol and cocaine use among a diverse sample of 268 HIV positive adults enrolled in an intervention for AIDS-related bereavement. Results indicated that the hypothesized model fit the study data. Male gender, PD indication, and social support had direct effects on substance use. PD had significant indirect effects on both alcohol and cocaine use, mediated by social support, but not by grief. Finally, both PD and social support had significant, but opposite, effects on grief. Implications for intervention and prevention efforts are discussed. PMID- 17846879 TI - Assessing stability between treatment planning documents in a system of care. AB - Two studies were performed to examine the presence and stability of specific recommendations for treatment practices in a system of care. Study 1 evaluated the reliability of an instrument designed to quantify specific elements of treatment planning documents. Study 2 used reliably coded data from Study 1 to assess stability of treatment practices and targets across the treatment planning process. This study indicated a generally low level of agreement of between documents, with many specific recommendations being dropped between stages of planning. The implications of these findings and the potential for future research are discussed. PMID- 17846880 TI - Inter-rater reliability of clinician-rated outcome measures in child and adolescent mental health services. AB - This study investigated the inter-rater reliability when 169 out of 171 clinicians working in 10 Norwegian child and adolescent mental health services rated 20 written vignettes using the following outcome measures: Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA), Children's Global Assessment Scale (CGAS) and Global Assessment of Psychosocial Disability (GAPD). Three clinicians rated both patients and vignettes. On vignettes the intraclass correlation coefficient (ICC) for the HoNOSCA total score was 0.81 (single scales 0.47-0.96), for the CGAS 0.61 and for the GAPD 0.60. The reliability was not lower on patients. The rater's profession, experience or clinic did not have effect on the scores. PMID- 17846881 TI - Reduction of connexin 43 in human cumulus cells yields good embryo competence during ICSI. AB - PURPOSE: The purpose of this study was to predict developmental competence of human oocytes during ICSI via analysis of connexin 43 (Cx43) in cumulus cells surrounding mature oocytes. MATERIALS AND METHODS: Human cumulus cells were manually separated from the oocyte-cumulus complex under a microscope. Cx43 mRNA was expressed by real-time quantitative polymerase chain reaction (RT-PCR) measurement in cumulus cells. RESULTS: There was no significant relationship between expression of Cx43 and fertilisation or cleavage rate. However, Cx43 expression was lower in the good morphology group (blastomeres>7 cells with fragmentation<10% on day 3) when compared to the other groups (p=0.035). CONCLUSIONS: These results suggest that full reduction of Cx43 expression on cumulus cells at the time of oocyte collection during ICSI is essential for developmental competence of human oocytes. PMID- 17846882 TI - Violent victimization in the community and children's subsequent peer rejection: the mediating role of emotion dysregulation. AB - This paper describes a short-term longitudinal study of the relation between violent victimization in the community and peer rejection among 199 children (mean age = 9.02 years) attending two urban Los Angeles area elementary schools. We used a multi-informant approach to assess victimization by community violence, peer group victimization, peer rejection, and impairments in emotion regulation. These data were collected annually for two consecutive school years. Violent victimization in the community predicted later peer rejection after accounting for the effects of initial levels of peer rejection. Analyses indicated that this relation was mediated by deficient emotion regulation skills. In addition, we found evidence that victimization by community violence and peer rejection are reciprocally related over time. The developmental implications of these findings are discussed. PMID- 17846883 TI - No association between the LRRK2 G2019S mutation and Alzheimer's disease in Italy. AB - AIMS: Investigation of the leucine-rich repeat kinase 2 (LRRK2) gene in late onset Alzheimer's disease (AD) patients to screen for the G2019S mutation, which is common in Parkinson's cases. METHODS: High-resolution melting analysis (HRMA) was used to screen a large sample of patients. The target sequence was amplified by standard PCR in the presence of an intercalating fluorescent dye. Heterozygotes were easily identified because the heteroduplexes produced changed the shape of the melting curve. RESULTS: In accordance to previous studies, we did not detect the G2019S mutation in any of the 769 Italian AD patients under study. CONCLUSIONS: HMRA allowed us to rapidly characterize a large number of samples for the LRRK2 G2019S mutation, which results as absent in a large AD data set. PMID- 17846884 TI - The effect of curcumin on ethanol induced changes in suprachiasmatic nucleus (SCN) and pineal. AB - (1) Circadian clocks have been localized to discrete sites within the nervous system of several organisms and in mammals to the suprachiasmatic nucleus (SCN) in the anterior hypothalamus. The SCN controls and regulates the production and discharge of melatonin (hormonal message of darkness) from the pineal gland via a multisynaptic efferent pathway. The nocturnal rise in melatonin production from serotonin results due to an increased activity of serotonin N-acetyl transferase (NAT). (2) The complex interaction between alcohol and biological clock need to be understood as alcoholism results in various clock linked neuronal disorders especially loss of memory and amnesia like state of consciousness, sleep disorders, insomnia, dementia etc. (3) Serotonin, 5-Hydroxy-tryptamine (5-HT) plays an important role in mediating alcohol's effects on the brain. Understanding the impact of alcohol consumption on circadian system is a pre requisite to help in treatment of alcohol induced neurological disorders. We, therefore, studied the effect of ethanol drinking and ethanol withdrawal on daily rhythms of serotonin and its metabolite, 5-hydroxy-indole acetic acid (5-HIAA) in SCN and Pineal of adult male Wistar rats maintained under light-dark (LD, 12:12) conditions. (4) Curcumin is well known for its protective properties such as antioxidant, anti-carcinogenic, anti-viral and anti-infectious etc. Hence, we studied the effect of curcumin on ethanol induced changes on 5-HT and 5-HIAA levels and rhythms in SCN and Pineal. (5) Ethanol withdrawal could not restore either rhythmicity or phases or levels of 5-HT and 5-HIAA. Curcumin administration resulted in partial restoration of daily 5-HT/5-HIAA ratio, with phase shifts in SCN and in Pineal. Understanding the impact of alcohol consumption on circadian system and the role of herbal medication on alcohol withdrawal will help in treatment of alcohol induced neurological disorders. PMID- 17846885 TI - In vitro effects of environmentally relevant polybrominated diphenyl ether (PBDE) congeners on calcium buffering mechanisms in rat brain. AB - Polybrominated diphenyl ethers (PBDEs) are widely used as additive flame retardants and have been detected in human blood, adipose tissue, and breast milk. Developmental and long-term exposures to these chemicals may pose a human health risk, especially to children. We have previously demonstrated that polychlorinated biphenyls (PCBs), which are structurally similar to PBDEs and cause neurotoxicity, perturb intracellular signaling events including calcium homeostasis and protein kinase C translocation, which are critical for neuronal function and development of the nervous system. The objective of the present study was to test whether environmentally relevant PBDE congeners 47 and 99 are also capable of disrupting Ca(2+) homeostasis. Calcium buffering was determined by measuring (45)Ca(2+)-uptake by microsomes and mitochondria, isolated from adult male rat brain (frontal cortex, cerebellum, hippocampus, and hypothalamus). Results show that PBDEs 47 and 99 inhibit both microsomal and mitochondrial (45)Ca(2+)-uptake in a concentration-dependent manner. The effect of these congeners on (45)Ca(2+)-uptake is similar in all four brain regions though the hypothalamus seems to be slightly more sensitive. Among the two preparations, the congeners inhibited (45)Ca(2+)-uptake in mitochondria to a greater extent than in microsomes. These results indicate that PBDE 47 and PBDE 99 congeners perturb calcium signaling in rat brain in a manner similar to PCB congeners, suggesting a common mode of action of these persistent organic pollutants. PMID- 17846886 TI - Subject-specific model estimation of cardiac output and blood volume during hemorrhage. AB - We have developed a novel method for estimating subject-specific hemodynamics during hemorrhage. First, a mathematical model representing a closed-loop circulation and baroreceptor feedback system was parameterized to match the baseline physiology of individual experimental subjects by fitting model results to 1 min of pre-injury data. This automated parameterization process matched pre injury measurements within 1.4 +/- 1.3% SD. Tuned parameters were then used in similar open-loop models to simulate dynamics post-injury. Cardiac output (CO) estimates were obtained continuously using post-injury measurements of arterial blood pressure (ABP) and heart rate (HR) as inputs to the first open-loop model. Secondarily, total blood volume (TBV) estimates were obtained by summing the blood volumes in all the circulatory segments of a second open-loop model that used measured CO as an additional input. We validated the estimation method by comparing model CO results to flowprobe measurements in 14 pigs. Overall, CO estimates had a Bland-Altman bias of -0.30 l/min with upper and lower limits of agreement 0.80 and -1.40 l/min. The negative bias is likely due to overestimation of the peripheral resistance response to hemorrhage. There was no reference measurement of TBV; however, the estimates appeared reasonable and clearly predicted survival versus death during the post-hemorrhage period. Both open-loop models ran in real time on a computer with a 2.4 GHz processor, and their clinical applicability in emergency care scenarios is discussed. PMID- 17846888 TI - Fibrogenesis in fatty liver associated with obesity and diabetes mellitus type 2. AB - Fatty liver in obese patients is emerging as one of the most common causes of chronic liver disease. Obese patients are at risk of developing type 2 diabetes mellitus (DM), and aggravating non-alcoholic fatty liver disease (NAFLD), developing into steatohepatitis (NASH) and hepatic fibrosis. Little is known of the possible impact on liver fibrogenesis of diabetes type 2 associated with obesity and NAFLD. Fifty-two morbidly obese patients were evaluated with complete clinical and laboratory medical assessment. Liver biopsy material was fixed in formalin, routinely processed to paraffin blocks, cut into 4-microm sections, stained with HE, PAS, Masson's trichrome and reticulin. Immunohistochemical stains included collagen IV, SMA and laminin. Within the initial group of 52, 25 patients had DM type 2, mean age 45.8 years. Patients with diabetes were older; had higher BMI, liver enzyme tests, glucose, cholesterol, and triglycerides; and lower albumin concentration. Livers of diabetics had significantly more severe steatosis and rich perisinusoidal collagen IV, laminin and SMA accumulation without histologically detectable NASH and irrespective of the degree of steatosis. Obese patients with type 2 DM and insulin resistance develop more severe NAFLD and early sinusoidal fibrosclerosis. PMID- 17846887 TI - Phlebotomy improves therapeutic response to interferon in patients with chronic hepatitis C: a meta-analysis of six prospective randomized controlled trials. AB - Prospective randomized controlled trials (RCTs) comparing phlebotomy and interferon (IFN) treatment to IFN alone in patients with chronic hepatitis C (CHC) have suggested a benefit for the phlebotomy group. However, statistical significance was achieved in only one of these trials. We performed a meta analysis of RCTs comparing phlebotomy and IFN to IFN alone for the treatment of CHC. The MEDLINE database and Cochrane registry of controlled trials were searched using the key words "phlebotomy" and "treatment of hepatitis C." Reference lists of review articles discussing the interaction between iron and CHC, and prospective RCTs comparing phlebotomy plus IFN therapy to IFN alone were searched to identify additional RCTs that compared phlebotomy plus IFN to IFN alone. Peto odds ratios with their 95% confidence intervals and Forrest plots were generated for each variable to assess the relationships among the studies that had provided that information. Statistical analysis was performed using Comprehensive META-Analysis version 2.0. Six prospective RCTs were identified: all used sustained viral response (SVR) as an endpoint. The three largest RCTs excluded patients with cirrhosis. Two RCTs specifically included only patients with either high ferritin or high hepatic iron content. IFN treatment regimes varied. Length of treatment varied between 6 and 12 months. The phlebotomy plus IFN group and the IFN group did not differ with respect to the percentage of patients with cirrhosis or genotype 1. SVR was attained in 50/182 (27%) patients in the phlebotomy plus IFN group, compared to 22/185 (12%) patients in the IFN group. Peto odds ratio for SVR in phlebotomy plus IFN group was 2.7; 95% CI 1.6 4.5, P < 0.0001. All five RCTs published in manuscript form showed a trend towards a benefit from the phlebotomy plus IFN in attaining SVR, and the results of the meta-analysis were not dependent on any single RCT, since excluding any single RCT did not change the results. Phlebotomy improves the SVR in response to IFN treatment in patients with CHC. Confirmation of this will require RCT with detailed pre-treatment iron studies and appropriately powered to demonstrate a statistically significant benefit. PMID- 17846889 TI - A polyp at the ureterosigmoidostomy orifice: a case report. PMID- 17846891 TI - Efficacy of a culturally adapted intervention for youth living with HIV in Uganda. AB - This study examined whether a culturally adapted version of a previously evaluated efficacious HIV prevention program reduced sexual risk behaviors of youth living with HIV (YLH) in Uganda. YLH, 14 to 21 years, were randomized to intervention (N = 50) or control (N = 50) conditions. Significantly more YLH in the intervention used condoms consistently and decreased their number of sexual partners in comparison to the control condition. Western interventions can be culturally adapted to retain efficacy in reducing the sexual risk behavior of YLH. PMID- 17846890 TI - Effects of friendship closeness in an adolescent group HIV prevention intervention. AB - Although many interventions for youth rely, explicitly or implicitly, on group effects, sparse theoretical or empirical attention has been paid to the rationale for choosing a small-group design. The present study assesses the role of friendship closeness among youth in prevention intervention groups in shaping their HIV risk-related attitudes, intentions, perceived self-efficacy and perceived norms. Data from an experimental test of a group HIV prevention intervention are used to assess the relationship of friendship on cognitive outcomes at posttest and 6-month follow-up, in a multilevel regression design. Friendship among group members was assessed at baseline and post-intervention, for youth in the experimental intervention and in a control, career exploration, condition. Level of friendship within the group was positively related to attendance and enjoyment of the intervention in the control group only. Most cognitive outcomes were unaffected by individual or group levels of friendship closeness, but those effects observed were opposite to those desired. Friendly groups were no more likely to converge in their cognitions over time than were less-friendly groups. The need for more research on the effects of friendship on intervention outcomes, and for multilevel analyses of group effects, are discussed. PMID- 17846892 TI - Non-uniform plasma leakage affects local hematocrit and blood flow: implications for inflammation and tumor perfusion. AB - Vessel leakiness is a hallmark of inflammation and cancer. In inflammation, plasma extravasation and leukocyte adhesion occur in a coordinated manner to enable the immune response, but also to maintain tissue perfusion. In tumors, similar mechanisms operate, but they are not well regulated. Therefore, blood perfusion in tumors is non-uniform, and delivery of blood-borne therapeutics is difficult. In order to analyze the interplay among plasma leakage, blood viscosity, and vessel geometry, we developed a mathematical model that explicitly includes blood cells, vessel branching, and focal leakage. The results show that local hemoconcentration due to plasma leakage can greatly increase the flow resistance in individual vascular segments, diverting flow to other regions. Similarly, leukocyte rolling can increase flow resistance by partially blocking flow. Vessel dilation can counter these effects, and likely occurs in inflammation to maintain blood flow. These results suggest that potential strategies for improving perfusion through tumor networks include (i) eliminating non-uniform plasma leakage, (ii) inhibiting leukocyte interactions, and (iii) preventing RBC aggregation in sluggish vessels. Normalization of tumor vessels by anti-angiogenic therapy may improve tumor perfusion via the first two mechanisms. PMID- 17846893 TI - A biodegradable slotted tube stent based on poly(L-lactide) and poly(4 hydroxybutyrate) for rapid balloon-expansion. AB - Safe vascular stent application requires rapid expansion of the stent to minimize the risk of procedural ischemia. While high expansion speeds can be achieved with metallic stents, they are not necessarily feasible with biodegradable polymeric stents due to the viscoelastic material behavior. This study reports on a novel biodegradable polymer blend material based on poly(L-lactide) (PLLA) and poly(4 hydroxybutyrate) (P4HB), and describes the mechanical properties and in vitro degradation behavior of a balloon-expandable slotted tube stent concept. The stent prototypes with nominal dimensions of 6.0 x 25 mm were manufactured by laser machining of solution cast PLLA/P4HB tubes (I.D. = 2.8 mm, d = 300 microm). The stents were expanded within 1 min by balloon inflation to 8 bar, after 5 min preconditioning in 37 degrees C water. Recoil and collapse pressure were 4.2% and 1.1 bar, respectively. During in vitro degradation collapse pressure initially increased to a maximum at 4 w and then decreased thereafter. After 48 w, molecular weight was decreased by 82%. In summary, the PLLA/P4HB slotted tube stents allowed for rapid balloon-expansion and exhibited adequate mechanical scaffolding properties suitable for a broad range of vascular and non-vascular applications. PMID- 17846894 TI - Biphasic finite element model of solute transport for direct infusion into nervous tissue. AB - Infusion-based techniques are promising drug delivery methods for treating diseases of the nervous system. Direct infusion into tissue parenchyma circumvents the blood-brain barrier, localizes delivery, and facilitates transport of macromolecular agents. Computational models that predict interstitial flow and solute transport may aid in protocol design and optimization. We have developed a biphasic finite element (FE) model that accounts for local, flow-induced tissue swelling around an infusion cavity. It solves for interstitial fluid flow, tissue deformation, and solute transport in surrounding isotropic gray matter. FE solutions for pressure-controlled infusion were validated by comparing with analytical solutions. The influence of deformation-dependent hydraulic permeability was considered. A transient, nonlinear relationship between infusion pressure and infusion rate was determined. The sensitivity of convection-dominated solute transport (i.e., albumin) over a range of nervous tissue properties was also simulated. Solute transport was found to be sensitive to pressure-induced swelling effects mainly in regions adjacent to the infusion cavity (r/a 0 T polymorphism and risk of prostate cancer: results from the CAPS study. AB - The methylenetetrahydrafolate reductase (MTHFR) enzyme may influence cancer development by affecting DNA methylation, synthesis and repair. The MTHFR 677C- >T single nucleotide polymorphism (SNP) has been associated with decreased enzyme activity and has therefore been implicated in cancer development. We analyzed the MTHFR 677C-->T SNP in 2,777 incident prostate cancer cases and 1,639 population controls from the CAncer Prostate in Sweden study (CAPS). No significant association was found overall between prostate cancer risk and the 677C-->T SNP (p = 0.27) with heterozygote (CT) and homozygote (TT) allele carriers showing ORs of 1.12 (95% CI: 0.98-1.27) and 1.02 (95% CI: 0.80-1.30), respectively. In the subgroup of low risk prostate cancer, heterozygote-but not homozygote-allele carriers displayed a slight over-risk with an OR of 1.21 (95% CI: 1.03-1.41). Among men under 65 years of age, the 677C-->T SNP was associated with prostate cancer risk (p = 0.007), with odds ratios of 1.33 (95% CI: 1.09-1.63) for heterozygote allele carriers and 0.86 (95% CI: 0.6-1.24) for homozygote allele carriers. However, this association was attributed to a shift in the genotype distribution in the young controls. In conclusion, our results do not provide strong support for the hypothesis that the MTHFR 677C-->T polymorphism is related to prostate cancer risk. PMID- 17846907 TI - Protein immunolocalization supports the presence of identical mechanisms of XY body formation in eutherians and marsupials. AB - The meiotic sex chromosomes of the American marsupials Monodelphis dimidiata and Didelphis albiventris were studied with electron microscopy (EM) and with immunofluorescence localization of meiotic proteins SYCP1 and SYCP3, and proteins essential for meiotic sex chromosome inactivation (MSCI), gamma-H2AX and BRCA1. The chromatin of the non-synaptic X and Y chromosomes contains gamma-H2AX, first as foci and then as homogeneous staining at late stages. The thick and split X and Y axes are labelled with BRCA1 except at one terminus. The bulgings of the axes contain SYCP1 as well as the inner side of the dense plate. The evenly spaced and highly packed chromatin fibres of the conjoined XY body in these species have the same behaviour and the same components (gamma-H2AX in the chromatin, BRCA1 in the axes) as in the XY body of eutherian species. These observations and recent data from the literature suggest that XY body formation is ancestral to the metatherian-eutherian divergence. PMID- 17846908 TI - Distribution of heavy metals in water, particulate matter and sediments of Gediz River (Eastern Aegean). AB - The present paper is the first document of heavy metal levels in surficial sediment, water and particulate matter of the Gediz River collected from five different sites in August, October 1998, February, June 1999. The present work attempts to establish the status of distribution and environmental implications of metals in the sediment, water and particulate matter and their possible sources of derivation. The concentrations of mercury ranged 0.037-0.81, 120-430; lead 0.59-1.5, 190-8,100; copper 0.24-1.6, 30-180; zinc 0.19-2.9, 10-80; manganese 30-170, 20-490; nickel 0.39-9.0, 100-510; iron 1.3-687, 100-6,200 microg/l in water and particulate matter, respectively. The maximum values in water were generally obtained in summer periods due to industrial and agricultural activities at Muradiye. The particulate metal concentrations also generally showed increased levels from the upper Gediz to the mouth of the river. Calculation of metal partition coefficients shows that the relative importance of the particulate and the water phases varies in response to water hydrochemistry and suspended solid content, but that most elements achieve a conditional equilibrium in the Gediz River. The metals ranged between Hg: 0.25-0.49, Cr: 59 814, Pb: 38-198, Cu: 15-148, Zn: 34-196, Mn: 235-1,371, Ni: 35-175, and Fe: 10,629-72,387 mg/kg in sediment. The significant increase of metals found in Muradiye suggested a pollution effect, related to anthropogenic wastes. Also, relatively high concentrations of Ni and Mn occurred in sampling site upstream, due to geochemical composition of the sediments. Maximum values of contamination factor for metals were noticed for sediment of Muradiye. The sampling stations have very high degree of contamination indicating serious anthropogenic pollution. PMID- 17846909 TI - Soil and vegetation carbon stocks in Brazilian Western Amazonia: relationships and ecological implications for natural landscapes. AB - The relationships between soils attributes, soil carbon stocks and vegetation carbon stocks are poorly know in Amazonia, even at regional scale. In this paper, we used the large and reliable soil database from Western Amazonia obtained from the RADAMBRASIL project and recent estimates of vegetation biomass to investigate some environmental relationships, quantifying C stocks of intact ecosystem in Western Amazonia. The results allowed separating the western Amazonia into 6 sectors, called pedo-zones: Roraima, Rio Negro Basin, Tertiary Plateaux of the Amazon, Javari-Jurua-Purus lowland, Acre Basin and Rondonia uplands. The highest C stock for the whole soil is observed in the Acre and in the Rio Negro sectors. In the former, this is due to the high nutrient status and high clay activity, whereas in the latter, it is attributed to a downward carbon movement attributed to widespread podzolization and arenization, forming spodic horizons. The youthful nature of shallow soils of the Javari-Jurua-Purus lowlands, associated with high Al, results in a high phytomass C/soil C ratio. A similar trend was observed for the shallow soils from the Roraima and Rondonia highlands. A consistent east-west decline in biomass carbon in the Rio Negro Basin sector is associated with increasing rainfall and higher sand amounts. It is related to lesser C protection and greater C loss of sandy soils, subjected to active chemical leaching and widespread podzolization. Also, these soils possess lower cation exchangeable capacity and lower water retention capacity. Zones where deeply weathered Latosols dominate have a overall pattern of high C sequestration, and greater than the shallower soils from the upper Amazon, west of Madeira and Negro rivers. This was attributed to deeper incorporation of carbon in these clayey and highly pedo-bioturbated soils. The results highlight the urgent need for refining soil data at an appropriate scale for C stocks calculations purposes in Amazonia. There is a risk of misinterpreting C stocks in Amazonia when such great pedological variability is not taken into account. PMID- 17846910 TI - Temporal-spatial epidemiology of foot-and-mouth disease outbreaks in Mongolia, 2000 - 2002. AB - Prior to 2000, foot-and-mouth disease (FMD) had not been observed in Mongolia since 1973; however, between April 2000 and July 2002, Mongolia reported 44 FMD outbreaks that affected cattle, sheep, goats, and camels. The objectives of this study were to describe the distributions of the 44 reported FMD outbreaks in Mongolia and to assess their spatial clustering and directions of movement. Official reports were collected to obtain the number and species of animals both affected and at risk, and the date and geographical coordinates of each outbreak. Significant global and local spatial clusters of reported FMD outbreaks were identified. Disease spread during the second epidemic moved 76 degrees northeast and the spread of the disease during the third epidemic moved 110 degrees northwest. FMD outbreaks were clustered intensely close to other FMD-positive counties. These findings can be used in the future to help plan prevention and control measures in high risk areas. PMID- 17846911 TI - Analytical performances of d-ROMs test and BAP test in canine plasma. Definition of the normal range in healthy Labrador dogs. AB - An high level of ROS (Reactive Oxygen Species), due to an increased production of oxidant species and/or a decreased efficacy of antioxidant system, can lead to oxidative stress, an emerging health risk factor involved in the aging and in many diseases, including inflammatory, infectious and degenerative disorders, either in humans or in animals. In the last years some assays panels have been developed to globally evaluate the oxidative balance by means of the concomitant assessment of ROS production and antioxidant system capability. In this report, the validation trials of d-ROMs (Reactive Oxygen Metabolites- derived compounds) and BAP (Biological Antioxidant Potential) tests in canine specie are described and also the specific referral ranges are calculated in a Labrador population. The results of linearity, precision and accuracy trials show that both tests exhibit good to excellent analytical performances. The possibility of measuring oxidative stress in vivo with simple, cheap and accurate tests, d-ROMs test and BAP test, provides for the veterinarians a very suitable tool to monitor oxidative stress and to correctly choice of eventual antioxidant supplementations in diseases proven related to oxidative stress in animals and particularly in dogs. Further studies will be useful to confirm this possibility. PMID- 17846912 TI - Serum and urine cystatin C levels in children with post-pyelonephritic renal scarring: a pilot study. AB - AIM: We aimed to investigate in children with a history of acute pyelonephritis the influence of unilateral post-pyelonephritic renal scarring detected by DMSA scan on serum (S(CysC)) and urine cystatin C (U(CysC)) as well as upon other traditional markers of renal damage. METHODS: Children with DMSA proven pyelonephritis (n = 28) were grouped as either scar [+] (n = 19, unilateral renal scarring) or scar [-] (no scarring, n = 9). The scar [+] group was further divided into scar-1 (differential DMSA uptake, Delta(DMSA) 10%, n = 11) subgroups. S(CysC), serum creatinine, urine NAG, microalbumin, protein, fractional sodium excretion (FE(Na)), tubular phosphate reabsorption (TPR), and U(CysC/Cr) were evaluated in all patients. RESULTS: Neither S(CysC) nor U(CysC) were affected by age, height, and weight. scar [+] versus scar [-] groups and scar-1 versus scar-2 subgroups were not different with regard to all studied parameters. S(CysC) did not increase in children with post-pyelonephritic unilateral renal scarring. However, 11 children with slightly increased (>0.95 mg/l) S(CysC) levels in scar [+] group tended to have higher Delta(DMSA), albeit not significantly. Furthermore, U(CysC/Cr) correlated well with urine microalbumin, NAG, and FE(Na) in all children and the scar [+] group (P < 0.05). CONCLUSION: S(CysC) and U(CysC) did not differ among pediatric patients with and without unilateral post-pyelonephritic renal scarring. However, Delta(DMSA) uptake between the two kidneys tended to be raised in children with S(CysC) levels higher than the reference ranges. Additionally, U(CysC/Cr) exhibits parallelism with tubular functions. PMID- 17846913 TI - Gender difference as regards myocardial protein oxidation in aged rats: male rats have increased oxidative protein damage. AB - OBJECTIVE: The reasons for the difference in life expectancy between males and females are still unknown. Previous studies have provided compelling evidence for the presence of oxidized proteins, and lipids in advanced human atherosclerotic lesions. The gender factor responsible for such protein oxidation is unknown and controversial. Our aim was to reveal the difference between myocardial protein and lipid oxidation parameters of male and female aged rats. METHODS: We investigated the relation between myocardial protein carbonyl (PCO) and other protein oxidation parameters such as advanced oxidation protein products (AOPP), nitrotyrosine (NT), protein hydroperoxide (P-OOH), and protein thiol (P-SH). Our study also covered other oxidative stress parameters, such as total thiol (T-SH), non-protein thiol (Np-SH), 4-hydroxyalkenal (4-HAE), malondialdehyde (MDA), reduced glutathione (GSH), and the glutathione disulfide (GSSG). RESULTS: Among the studied parameters, myocardial PCO, AOPP, NT, Np-SH, GSH, Fe(2+) levels and the redox index (RI) of male rats were significantly higher than in the female group. On the other hand, P-OOH, P-SH, T-SH, 4-HAE, and MDA levels were all found to be not different. CONCLUSIONS: These data support the hypothesis that elevated levels of PCO, AOPP, and NT contribute to the extent of protein, but not lipid, oxidation in aged male rats. We are of the conviction that the increased myocardial Np-SH, GSH and RI levels that we have determined in aged male rats may be a protective factor in propagation of protein oxidation. Our findings support our conviction that protein and lipid oxidation, in the myocardial tissue of aged rats, have a controlling role in differing regulating mechanisms through gender differences. PMID- 17846915 TI - Extraterrestrial flux of potentially prebiotic C, N, and P to the early Earth. AB - With growing evidence for a heavy bombardment period ending 4-3.8 billion years ago, meteorites and comets may have been an important source of prebiotic carbon, nitrogen, and phosphorus on the early Earth. Life may have originated shortly after the late-heavy bombardment, when concentrations of organic compounds and reactive phosphorus were enough to "kick life into gear". This work quantifies the sources of potentially prebiotic, extraterrestrial C, N, and P and correlates these fluxes with a comparison to total Ir fluxes, and estimates the effect of atmosphere on the survival of material. We find (1) that carbonaceous chondrites were not a good source of organic compounds, but interplanetary dust particles provided a constant, steady flux of organic compounds to the surface of the Earth, (2) extraterrestrial metallic material was much more abundant on the early Earth, and delivered reactive P in the form of phosphide minerals to the Earth's surface, and (3) large impacts provided substantial local enrichments of potentially prebiotic reagents. These results help elucidate the potential role of extraterrestrial matter in the origin of life. PMID- 17846914 TI - Selenite transiently represses transcription of photosynthesis-related genes in potato leaves. AB - A striking response of potato leaves to aspersion with selenite was observed at the transcriptional level by means of cDNA microarrays analysis. This response is characterized by a general transient repression of genes coding for components of photosynthetic systems and of other light-regulated genes. In particular, maximal repression was observed 8 h after selenite aspersion, while 24 h after the treatment a complete recovery of normal transcriptional levels was detected. Another general feature of the transcriptional response to selenite is represented by the transcriptional induction of genes related to amino acid metabolism, and to stress defense; interestingly, two genes coding for glutathione S-transferases were found early-induced upon selenite treatment. PMID- 17846916 TI - The response of patients with phenylketonuria and elevated serum phenylalanine to treatment with oral sapropterin dihydrochloride (6R-tetrahydrobiopterin): a phase II, multicentre, open-label, screening study. AB - This study aimed to evaluate the response to and safety of an 8-day course of sapropterin dihydrochloride (6R-tetrahydrobiopterin or 6R-BH4) 10 mg/kg per day in patients with phenylketonuria (PKU), who have elevated blood phenylalanine (Phe) levels, and to identify a suitable cohort of patients who would respond to sapropterin dihydrochloride treatment with a reduction in blood Phe level. Eligible patients were aged > or = 8 years, had blood Phe levels > or = 450 micromol/L and were not adhering to a Phe-restricted diet. Suitable patients were identified by a > or = 30% reduction in blood Phe level from baseline to day 8 following sapropterin dihydrochloride treatment. The proportion of patients who met these criteria was calculated for the overall population and by baseline Phe level (< 600, 600 to < 900, 900 to < 1200 and > or = 1200 micromol/L). In total, 485/490 patients completed the study and 20% (96/485) were identified as patients who would respond to sapropterin dihydrochloride. A reduction in Phe level was observed in all subgroups, although response was greater in patients with lower baseline Phe levels. Wide variability in response was seen across all baseline Phe subgroups. The majority of adverse events were mild and all resolved without complications. Sapropterin dihydrochloride was well tolerated and reduced blood Phe levels across all PKU phenotypes tested. Variability in reduction of Phe indicates that the response to sapropterin dihydrochloride cannot be predicted by baseline Phe level. PMID- 17846918 TI - Impaired right ventricular function in adenotonsillar hypertrophy. AB - OBJECTIVE: Adenotonsillar hypertrophy (ATH) causing upper airway obstruction and obstructive sleep apnea (OSA) syndrome and may lead to the pulmonary hypertension and cor pulmonale. This study was designed to determine the clinical value of right ventricular (RV) myocardial performance index (MPI) in ATH. The effects of adenotonsillectomy on MPI were also assessed. METHODS: Twenty-one children with grade 3 and grade 4 ATH and 21 age-and-sex matched healthy children were enrolled. MPI, defined as the sum of isovolumetric contraction and relaxation time divided by ejection time, was measured by using Doppler echocardiography preoperatively and postoperatively in all subjects. The quality of life in children was also assessed with obstructive sleep disorder questionnaire (OSA 18). RESULTS: The RV MPI in patients with ATH was significantly higher than the control group (0.41 +/- 0.06 vs. 0.29 +/- 0.07; P < .001). It showed a strong correlation with mean pulmonary artery pressure and OSA-18 survey score (r = 0.71; P < .005 and (r = 0.64; P < .01, respectively). The RV MPI and OSA-18 survey score decreased significantly after the relief of upper airway obstruction by adenotonsillectomy (from 0.41 +/- 0.06 to 0.31 +/- 0.03; P < .001 and from 83 +/- 27 to 36 +/- 12; P < .0001, respectively). The RV MPI in postoperative group was similar to control group. CONCLUSION: Our findings support that advanced stage of ATH is associated with impaired RV functions, which were recovered postoperatively. PMID- 17846917 TI - Neurodegeneration and chronic renal failure in methylmalonic aciduria--a pathophysiological approach. AB - In the last decades the survival of patients with methylmalonic aciduria has been improved. However, the overall outcome of affected patients remains disappointing. The disease course is often complicated by acute life-threatening metabolic crises, which can result in multiple organ failure or even death, resembling primary defects of mitochondrial energy metabolism. Biochemical abnormalities during metabolic derangement, such as metabolic acidosis, ketonaemia/ketonuria, lactic acidosis, hypoglycaemia and hyperammonaemia, suggest mitochondrial dysfunction. In addition, long-term complications such as chronic renal failure and neurological disease are frequently found. Neuropathophysiological studies have focused on various effects caused by accumulation of putatively toxic organic acids, the so-called 'toxic metabolite' hypothesis. In previous studies, methylmalonate (MMA) has been considered as the major neurotoxin in methylmalonic aciduria, whereas more recent studies have highlighted a synergistic inhibition of mitochondrial energy metabolism (pyruvate dehydrogenase complex, tricarboxylic acid cycle, respiratory chain, mitochondrial salvage pathway of deoxyribonucleoside triphosphate (dNTP)) induced by propionyl CoA, 2-methylcitrate and MMA as the key pathomechanism of inherited disorders of propionate metabolism. Intracerebral accumulation of toxic metabolites ('trapping' hypothesis') is considered a biochemical risk factor for neurodegeneration. Secondary effects of mitochondrial dysfunction, such as oxidative stress and impaired mtDNA homeostasis, contribute to pathogenesis of these disorders. The underlying pathomechanisms of chronic renal insufficiency in methylmalonic acidurias are not yet understood. We hypothesize that renal and cerebral pathomechanisms share some similarities, such as an involvement of dicarboxylic acid transport. This review aims to give a comprehensive overview on recent pathomechanistic concepts for methylmalonic acidurias. PMID- 17846919 TI - Identification, expression and tissue distribution of a renalase homologue from mouse. AB - FAD (flavin adenine dinucleotide)-dependent monoamine oxidases play very important roles in many biological processes. A novel monoamine oxidase, named renalase, has been identified in human kidney recently and is found to be markedly reduced in patients with end-stage renal disease (ESRD). Here, we reported the identification of a renalase homologue from mouse, termed mMAO-C (mouse monoamine oxidase-C) after the monoamine oxidase-A and -B (MAO-A and -B). This gene locates on the mouse chromosome 19C1 and its coding region spans 7 exons. The deuced amino acid sequences were predicted to contain a typical secretive signal peptide and a conserved amine oxidase domain. Phylogenetic analysis and multiple sequences alignment indicated that mMAO-C-like sequences exist in all examined species and share significant similarities. This gene has been submitted to the NCBI GenBank database (Accession number: DQ788834). With expression vectors generated from the cloned mMAO-C gene, exogenous protein was effectively expressed in both prokaryotic and eukaryotic cells. Recombinant mMAO C protein was secreted out of human cell lines, indicating the biological function of its signal peptide. Moreover, tissue expression pattern analysis revealed that mMAO-C gene is predominantly expressed in the mouse kidney and testicle, which implies that kidney and testicle are the main sources of renalase secretion. Shortly, this study provides an insight into understanding the physiological and biological functions of mMAO-C and its homologues in endocrine. PMID- 17846920 TI - Are heart valves from donors over 65 years of age morphologically suitable for transplantation? AB - Since there is no upper age limit for general organ donation, unlike heart valve donation, and since a quarter of all organ donors are 65 years and older, we examined whether the heart valves from these donors are suitable as allografts. In the period 1999-2004 the aortic valve and pulmonary valve of 100 organ donors above 65 years of age were examined to establish whether they would have been suitable as valve grafts. To compare the valve grafts above and below the age limit of 65 years, we used data on the aortic and pulmonary valves of 380 organ donors below the age limit in the same time period. Examination of the 200 heart valves showed that - just like valves from donors below the age limit - 100 of them would have met the medical quality standards for transplantation, which discriminate among optimal, suitable and unsuitable tissue morphology. The morphological suitability of the aortic valves decreases rapidly during the 4th decade of life and near to the age limit only 6% of them are accepted as grafts. The rate of potentially acceptable aortic valve grafts from organ donors aged over 65 years of 15% is also small. By contrast, the pulmonary valves are not affected by age-related tissue changes that might reduce their transplantability. The predominant majority (85%) of potential pulmonary valve grafts from organ donors over 65 years of age fulfilled the acceptance criteria, half of them (48%) even showing good tissue quality. In light of these results the age limit was raised to 70 years in 2005. PMID- 17846921 TI - Neuroprotection and free radical scavenging effects of Osmanthus fragrans. AB - The ethanol extract of dried flowers Osmanthus fragrans (OFE) was assessed for free radical scavenging effects measured by the bleaching of the 1,1-diphenyl-2 picryl-hydrazyl (DPPH) radical, scavenging of the hydroxyl anion, investigation of the ferric reducing/antioxidant power (FRAP) and lipid-peroxidation inhibition in rat tissues. OFE contained a high amount of total flavonoid and polyphenol. OFE presented the effects in the metal reducing power, FRAP assay with IC(50) values of 0.23 microg/ml, and 7.74 microg/ml, respectively. OFE presented similar activities toward the DPPH and hydroxyl anion scavenging ability with IC(50) values of 10 microg/ml. OFE with IC(50 )values between 46 and 97 microg/ml inhibited lipid peroxidation initiated by ferrous chloride in rat brain, liver, heart and kidney mitochodrias. Moreover, the neuroprotective activity of OFE was investigated under different insults (glutamate, arachidonic acid, and 6 hydroxydopamine) in Wistar rat primary cortical neurons. OFE with EC(50 )values between 66 and 165 microg/ml attenuated the neurotoxicity on MTT and LDH assays. In addition, the AKT protein expression of excitotoxicity and oxidative stress was displayed by western blotting analysis. OFE could up-regulate the glutamate and 6-OHDA decreased AKT expression. This is the first demonstration of the neuroprotective, free radical scavenging and anti-oxidative effects of O. fragrans. PMID- 17846922 TI - Amyloid peptides and proteins in review. AB - Amyloids are filamentous protein deposits ranging in size from nanometres to microns and composed of aggregated peptide beta-sheets formed from parallel or anti-parallel alignments of peptide beta-strands. Amyloid-forming proteins have attracted a great deal of recent attention because of their association with over 30 diseases, notably neurodegenerative conditions like Alzheimer's, Huntington's, Parkinson's, Creutzfeldt-Jacob and prion disorders, but also systemic diseases such as amyotrophic lateral sclerosis (Lou Gehrig's disease) and type II diabetes. These diseases are all thought to involve important conformational changes in proteins, sometimes termed misfolding, that usually produce beta-sheet structures with a strong tendency to aggregate into water-insoluble fibrous polymers. Reasons for such conformational changes in vivo are still unclear. Intermediate aggregated state(s), rather than precipitated insoluble polymeric aggregates, have recently been implicated in cellular toxicity and may be the source of aberrant pathology in amyloid diseases. Numerous in vitro studies of short and medium length peptides that form amyloids have provided some clues to amyloid formation, with an alpha-helix to beta-sheet folding transition sometimes implicated as an intermediary step leading to amyloid formation. More recently, quite a few non-pathological amyloidogenic proteins have also been identified and physiological properties have been ascribed, challenging previous implications that amyloids were always disease causing. This article summarises a great deal of current knowledge on the occurrence, structure, folding pathways, chemistry and biology associated with amyloidogenic peptides and proteins and highlights some key factors that have been found to influence amyloidogenesis. PMID- 17846923 TI - Assigning functions to genes--the main challenge of the post-genomics era. AB - Genome-sequencing projects yield enormous amounts of information that can lead to revolutions in our understanding of life and provide new platforms for the treatment of human diseases. However, DNA sequencing alone does not provide enough information to determine the molecular pathways of an organism in healthy and disease states. A huge number of gene products await functional characterization. Hence, there is a strong demand for technological solutions that help to assign the functions of proteins and genes. This review discusses high-throughput molecular biology methods, which promise to meet the challenges of the post-genomic era. PMID- 17846924 TI - New ESH/ESC guidelines signal progress in hypertension management. PMID- 17846925 TI - 2007 ESH-ESC Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). PMID- 17846926 TI - Survey assessment of worker dermal exposure and underlying behavioral determinants. AB - Within the workplace, there is less reliance on engineering controls for dermal exposure protection and more reliance on the worker's motivation and training in use of personal protective equipment. Behavior thus becomes a significant determinant of dermal exposure, and its assessment paramount in examining and understanding factors influencing exposure. The main objectives of this study were to: (i) assess worker knowledge, attitudes, and perceptions (KAP) of workplace dermal hazards using a self-complete questionnaire and to examine KAP associations with behavior and exposure; (ii) compare worker and manager scores to identify potential gaps in KAP between the two groups; (iii) utilize a semiquantitative observational DeRmal Exposure Assessment Methodology (DREAM) to evaluate worker dermal exposure; and (iv) identify potential behavioral factors underlying exposure using DREAM and KAP. Nineteen industries across the Baltimore, Md. and Lancaster, Pa., regions participated in the study including a total of 89 workers and 17 managers. The scales within the KAP questionnaire that served as the outcome measure included knowledge, training, behavior, behavior beliefs, information beliefs, self-efficacy, and overall beliefs. DREAM scores ranged from 0.15 to 545 with a median of 8 and a mean (SD) of 22 (62.5). Whereas worker self-efficacy with respect to PPE use, and the group "workers with 10-20 years of experience" were marginally positively associated with protective behavior (p < 0.08 and p < 0.06, respectively), a question related to barriers to PPE use was negatively associated with precautionary behavior (p < 0.01). Dermal exposure was positively associated with workers in the age group 40-49 years as compared with those less than 40 years of age (OR = 4.86, 95% CI = 0.93, 25.62). There were no statistically significant associations between KAP and DREAM. This is one of the first studies to begin to elucidate worker knowledge, attitudes, and perceptions that underlie behaviors that lead to occupational dermal exposures. Results of the KAP questionnaire can inform strategies to improve awareness and protective practices in the workplace through factors such as increased worker dermal hazard knowledge, well-informed company PPE selection and availability, and improved worker training. PMID- 17846927 TI - Nontuberculous mycobacteria in aerosol droplets and bulk water samples from therapy pools and hot tubs. AB - Hot tub exposure has been causally associated with a steroid-responsive, granulomatous lung disease featuring nontuberculous mycobacterial (NTM) growth in both clinical and environmental samples. Little is known regarding prevalence of and risk factors for NTM-contamination and associated illness in these settings. In this study, the frequency of NTM growth and aerosolization in 18 public hot tubs and warm water therapy pools and the factors associated with mycobacterial growth were analyzed. Each site was characterized by water chemistry analysis; a questionnaire on maintenance, disinfection, and water quality; and air and water sampling for quantitative NTM culture. NTM were detected in air or water from 13/18 (72%) sites; a strong correlation was found between the maximum air and water NTM concentrations (rho 0.49, p = 0.04). Use of halogen (chlorine or bromine) disinfection was associated with significantly lower air and water concentrations of NTM compared with disinfection using ultraviolet light and hydrogen peroxide (p = 0.01-0.04). Higher water turnover rates were also associated with lower air and water NTM concentrations (p = 0.02-0.03). These findings suggest that NTM are frequently detectable in the air and water of spas and therapy pools and that particular maintenance and disinfection approaches affect NTM bioaerosol concentrations in these settings. PMID- 17846928 TI - Must undergraduate medical education be hospital-based? PMID- 17846929 TI - Towards fragmentation of general practice and primary healthcare in Finland? PMID- 17846930 TI - The association between patient shortage and patient satisfaction with general practitioners. AB - OBJECTIVE: The aim of the study was to explore whether or not the influx of patients to a GP's practice is associated with satisfaction with the GP. DESIGN: Persons in the Norwegian Living Condition Survey answered a questionnaire on satisfaction with their GP. The data on satisfaction were merged with registered information on the GPs and the GPs' patient lists from the National Insurance Administration, with registered information on the sample's sociodemographic background, and on their resident municipality from Statistics Norway. SETTING: A representative sample of 2326 persons answered the questionnaire. This constituted persons in the survey who had visited their GP during the last six months. MAIN OUTCOME MEASURE: Satisfaction with the GP's interpersonal skills, the GP's medical skills, the GP's use of time, general accessibility to the GP, and the GP's role as a gatekeeper. RESULTS: Persons listed with a GP who experience patient shortage were less satisfied than others along four dimensions of satisfaction: the GP's interpersonal skills, the GP's medical skills, the GP's referral practices, and the consultation lengths the GP offered. The GP's age and gender, characteristics of the patient, and characteristics of the organization of primary care had minor influence. CONCLUSION: Whether or not a GP experiences patient shortage is associated with patient satisfaction. Whether or not the lower patient satisfaction is a result of patient shortage or vice versa is not known. PMID- 17846931 TI - Self-monitoring of blood glucose and glycaemic control in type 2 diabetes. AB - OBJECTIVE: Previous studies have shown inconsistent results with regard to whether or not self-monitoring of blood glucose (SMBG) is related to better glycaemic control in type 2 diabetes. The aim of this study was to explore the use of SMBG and its association with glycaemic control in patients with type 2 diabetes in primary care. DESIGN: A cross-sectional observational study was conducted in 2003 at 18 primary health care centres in Sweden, in which all known patients with diabetes were surveyed. The study included 6495 patients with type 2 diabetes. A sample of 896 patients was selected for further exploration of data from medical records. A telephone interview was performed with all patients in this group using SMBG (533 patients). RESULTS: There were no differences in HbA1c levels between users (6.9%) and non-users (6.8%) of SMBG in patients treated with insulin or in patients treated with oral agents (6.3% in both groups). In patients treated with diet only, users of SMBG had higher levels of HbA1c compared with non-users (5.5% vs. 5.4%, p =0.002). Comparing medical records between users and non-users of SMBG showed no differences in diabetes-related complications in any treatment category group. CONCLUSION: The use of SMBG was not associated with improved glycaemic control in any therapy category of patients with type 2 diabetes in primary care. The absence of difference in glycaemic control between users and non-users of SMBG could not be explained by differences in comorbidity between users and non-users of SMBG. PMID- 17846932 TI - Recognition of fasting or overall hyperglycaemia when starting insulin treatment in patients with type 2 diabetes in general practice. AB - OBJECTIVE: The efficacy of various regimens of initial insulin treatment in poorly controlled type 2 diabetes was compared with regard to diurnal glucose variation. DESIGN: Randomized controlled trial. Setting. Insulin therapy initiated on hospital wards, follow-up as outpatients for 12 months. SUBJECTS: Fifty-two type 2 diabetic patients (HbA1c >7.5%, mean 9.8%) on maximal oral therapy. Interventions. Insulin only (IO), bedtime insulin with sulphonylurea (glipizide) (IS), or bedtime insulin with metformin (IM). MAIN OUTCOME MEASURES: HbA1c and body weight. RESULTS: HbA1c decreased on average by 1.8, 1.0 and 1.5 percentage points in the IO, IS, and IM groups, respectively (p always <0.025). Body weight increased, most in the IO patients (+6.2 kg), least in the IM patients (+3.4 kg). Analysing all treatment groups combined, a similar HbA1c reduction was observed in patients with overall hyperglycaemia (low fasting plasma glucose/HbA1c ratio) and in patients with fasting hyperglycaemia (high fasting plasma glucose/HbA1c ratio). Within the overall hyperglycaemia group, the IS and IM patients had smaller decreases in HbA1c (-1.5 and -1.3 percentage points, respectively) than the IO patients (-2.7 percentage points). On the other hand, within the fasting hyperglycaemia group HbA1c reductions were -1.2, -0.8 and -1.5 percentage points, in the IO, IS, and IM groups, respectively. CONCLUSION: Not all poorly controlled type 2 diabetic patients should automatically be treated with an oral agent and bedtime insulin. Two daily insulin injections is a valid choice, particularly if the patient has overall hyperglycaemia. PMID- 17846934 TI - Perceived risk of osteoporosis: restricted physical activities? Qualitative interview study with women in their sixties. AB - OBJECTIVE: To explore elderly women's physical activity in relation to their perception of the risk of osteoporosis. DESIGN: Qualitative study using in-depth interviews. SETTING: Informants were purposely selected from a Danish population based, age-specific cohort study conducted in the county of Copenhagen with people born in 1936. SUBJECTS: Women in their sixties. RESULTS: Women who perceived a current risk of osteoporosis tended to reduce their physical activity in an attempt to reduce the risk of bone damage. This behaviour was related to the imagined fragility of the bones (the risk inside the body), and the actual situations (the risk outside the body), including places and activities. Knowledge of a reduced bone mass reinforced the women's uncertainty about what their bones could endure. Experiences managing physical activity without injury resulted in reinterpretations of their risk of bone fractures and increased physical activity. CONCLUSIONS: Perceived risk of osteoporosis may lead to decreased physical activity and hence actually increase the risk. When informing individuals about health risk people's images and imaginations of the actual risk have to be acknowledged. When a bone scan is being considered, explicit advice encouraging physical activity - especially the weight-bearing kind - should be stressed. PMID- 17846933 TI - Effects of treatment with a commercially available St John's Wort product (Movina) on cholesterol levels in patients with hypercholesterolemia treated with simvastatin. AB - OBJECTIVE: To assess the effect of treatment with a St John's Wort product (Movina) on cholesterol levels (total cholesterol, LDL-cholesterol, and HDL cholesterol) in patients with hypercholesterolemia on treatment with a stable dose of simvastatin. DESIGN: Controlled, randomized, open, crossover pharmacodynamic study. SETTING: Two primary healthcare centres. Intervention. Patients were treated with Movina one tablet (containing 300 mg of Hypericum perforatum) twice daily and control (a commercially available multivitamin tablet, Vitamineral). The trial started with a run-in period of 4 weeks. Then the treatment order between control and active treatment was decided (randomization using sealed envelopes). The duration of each treatment period was 4 weeks and simvastatin treatment was kept unchanged during the whole study period (12 weeks). SUBJECTS: Twenty-four patients with hypercholesterolemia treated with a stable dose of simvastatin (10-40 mg daily) for at least three months. MAIN OUTCOME MEASURES: Assessments of total cholesterol, HDL- cholesterol, LDL cholesterol, and triglycerides were performed in the morning with the patients in a fasting condition. RESULTS: All patients completed the study. LDL-cholesterol was significantly increased during active treatment compared with control. Thus, the mean LDL-cholesterol after 4 weeks' active treatment was 2.72 mmol/L compared with 2.30 mmol/L after treatment with control (p <0.0001). An increase in total cholesterol was also observed (5.08 mmol/L compared with 4.56 mmol/L, p <0.0001). CONCLUSION: Products containing St John's Wort should not be given to patients with hypercholesterolemia who are on treatment with simvastatin. PMID- 17846935 TI - Evaluation of phenoxymethylpenicillin treatment of acute otitis media in children aged 2-16. AB - OBJECTIVE: To study the clinical recovery from acute otitis media (AOM) in children, 2-16 years of age, managed with or without treatment with phenoxymethylpenicillin (PcV). DESIGN: An open, prospective randomized trial. Children aged between 2 and 16 years, presenting with one- or double-sided AOM (without perforation) with symptom duration of less than four days, were included. The children were randomized to PcV for five days or to no primary antibiotic treatment. A health score and compliance were registered on a daily basis for seven days. SETTING: A total of 32 health centres and 72 GPs in south east Sweden. Subjects. Children aged 2-16 presenting with earache. MAIN OUTCOME MEASURES: Recovery time, symptom duration, frequency of complications (up to three months) and consumption of healthcare services independent of treatment with or without antibiotics. RESULTS: A total of 179 patients carried out the trial; 92 were randomized to PcV, 87 to no primary antibiotic treatment. The median recovery time was four days in both groups. Patients who received PcV had less pain (p <0.001) and used fewer analgesics. There were no significant differences in the number of middle-ear effusions or perforations at the final control after three months. Children randomized to PcV treatment consulted less (p <0.001) during the first seven days. CONCLUSIONS: Our investigation supports that PcV treatment of AOM does not affect the recovery time or complication rates. PcV provided some symptomatic benefit in the treatment of AOM in otherwise healthy children, aged 2-16 years. PMID- 17846936 TI - New rules meet established sickness certification practice: a focus-group study on the introduction of functional assessments in Norwegian primary care. AB - OBJECTIVE: To explore how general practitioners view and handle new standards for functional assessments in sickness certification practice. DESIGN: Qualitative study using focus group interviews. Data were analysed according to Giorgi's phenomenological approach and supported by theories on knowledge. SETTING: General practitioners from three neighbouring counties in Norway. SUBJECTS: Four focus groups with a total of 23 participants were recruited through the Norwegian Medical Association and its Continuous Medical Education system. RESULTS: The participants reported difficulties and reluctance to act in accordance with new functional assessment demands on both a practical and a conceptual level. In established sickness certification practice functional assessment was described as an unspoken part of the medical examination. After the introduction of formal, written functional assessments they identified problems of terminology, communication, and trust. Strategies were developed to circumvent these problems. CONCLUSIONS: A gap was noticeable between the participants' established practice and the new standards' demand for a more theoretical and communicative functional assessment. The general lack of training, being confronted with new terminology, and increasingly high pressure to reduce sickness absences create an atmosphere of insecurity when assessing function. PMID- 17846937 TI - Frequency and nature of problems associated with sickness certification tasks: a cross-sectional questionnaire study of 5455 physicians. AB - OBJECTIVE: To study the frequency and nature of problems associated with physicians' sickness certification practices. DESIGN: Cross-sectional questionnaire study. SETTING: Stockholm and Ostergotland Counties in Sweden. SUBJECTS: Physicians aged < or = 64 years, n =7665, response rate 71% (n =5455). MAIN OUTCOME MEASURES: The frequency of consultations involving sickness certification, the frequency and nature of problems related to sickness certification. RESULTS: A total of 74% (n =4019) of the respondents had consultations including sickness certification at least a few times a year. About half of these physicians had sickness certification cases at least six times a week, and 1 out of 10 (9.4%) had this more than 20 times a week. The items that the highest percentage of physicians rated as very or fairly problematic included: handling conflicts with patients over certification, assessing work ability, estimating optimal length and degree of absence, and managing prolongation of sick leave initially certified by another physician. There were large differences in frequency and nature of problems between different types of clinics/practices. General practitioners had the highest frequency of problems concerning sickness certification while the lowest was found among specialists in internal medicine and surgery. CONCLUSION: Sickness certification should be recognized as an important task also for physicians other than general practitioners. The physicians experienced problems with numerous tasks related to sickness certification and these varied considerably between types of clinics. The high rate of problems experienced may have consequences for the physicians' work situation, for patients, and for society. PMID- 17846938 TI - Effect of an integrated primary care model on the management of middle-aged and old patients with obstructive lung diseases. AB - OBJECTIVE: To investigate the effect of a primary care model for COPD on process of care and patient outcome. DESIGN: Controlled study with delayed intervention in control group. SETTING: The GP delegates tasks to a COPD support service (CSS) and a practice nurse. The CSS offers logistic support to the practice through a patient register and recall system for annual history-taking and lung function measurement. It also forms the link with the chest physician for diagnostic and therapeutic advice. The practice nurse's most important tasks are education and counselling. SUBJECTS: A total of 44 practices (n =22 for intervention and n =22 for control group) and 260 of their patients > or = 40 years with obstructive lung diseases. RESULTS: Within the intervention group planned visits increased from 16% to 44% and from 19% to 25% in the control condition (difference between groups p =0.014). Annual lung function measurement rose from 17% to 67% in the intervention and from 11% to 18% in the control group (difference between groups p =0.001). Compared with control, more but not statistically significant smokers received periodic advice to quit smoking (p =0.16). At baseline 41% of the intervention group were using their inhalers correctly and this increased to 54% after two years; it decreased in the control group from 47 to 29% (difference between groups p =0.002). The percentage of patients without exacerbation did not change significantly compared with the control condition. The percentage of the intervention group not needing emergency medication rose from 79% to 84% but decreased in the controls from 81 to 76% (difference between groups p =0.08). CONCLUSION: Combining different disciplines in one model has a positive effect on compliance with recommendations for monitoring patients, and improves the care process and some patient outcomes. PMID- 17846939 TI - [Bevacizumab or ranibizumab, or the tale of Robin Hood and King Richard Lion Heart]. PMID- 17846940 TI - [Preservatives in ophthalmic formulations: an overview]. PMID- 17846941 TI - [Either we protocolize ourselves or they protocolize us: the judicialization of the ophthalmology]. PMID- 17846942 TI - [Multiple neoplasms in patients with uveal melanoma]. AB - PURPOSE: To study the prevalence of multiple neoplasms in patients affected by uveal melanoma in Spain and to relate these with survival. METHOD: We carried out a longitudinal prospective study of the prevalence of multiple neoplasms in patients diagnosed to have a uveal melanoma during the years 1984-2005. The data has been analysed for the following variables: age, sex, date of diagnosis, affected eye, origin and tumoral size, classification according to COMS (Collaborative Ocular Melanoma Study), time of follow-up, presence of other neoplasms, current clinical state, date and cause of death. RESULTS: Three hundred and five patients affected by uveal melanoma have been studied in the Ocular Oncology Unit of our institution; 24 patients (7.9%) had evidence in their medical reports of one or more additional neoplasms. Excluding cutaneous neoplasms originating in basal cells, this number reduced to 22 patients (7.2%). We did not find any statistically significant differences among the presentation age, sex or localization of the melanoma (ciliary body or choroid) and the presence or absence of a second neoplasm. When we analysed the proportion of patients with metastatic disease (both alive and dead) who presented with a second neoplasm (40.9%), we found a statistically significant relationship between these variables (Chi-square test, p=0.004). CONCLUSIONS: We have observed a percentage of second neoplasms similar to that described in other international studies. We did not find a larger proportion with a second neoplasm according to the sex, age, or tumoral localization, nor did we observe a higher frequency of any particular second neoplasm. We have defined a relationship between metastasic uveal melanoma, and the development of a second neoplasm, which clearly indicates a need for increased systemic follow-up in such patients. PMID- 17846943 TI - [An experimental model to measure real intraocular pressure (IOP) during LASIK]. AB - PURPOSE: To design a model to measure real IOP during lasik in pig eyes. METHODS: A reusable blood pressure transducer was used. Each eye was placed on a stand with sufficient support for the surgical procedure. The globes were inflated with 5% glucosated solution through the optic nerve to attain an IOP of 10-20 mmHg. A 27-gauge catheter was then inserted from the pars plana to the anterior chamber cavity. Real IOP was transmitted via the catheter liquid column to an external sensor. A suction ring was applied and a flap was created. During the procedure, IOP was registered with the ML110 Bridge Amplifier connected to a baro transducer. RESULTS: Values of real IOP were measured in freshly enucleated pig eyes during the lasik procedure. The model was able to instantaneously register the changes in IOP induced by the application of a suction ring and the creation of a flap in the pig eyes with good reproducibility. At the end of the procedure the IOP values remained stable. CONCLUSIONS: We have developed an experimental model to observe the course of suctioning and changes in IOP simultaneously. This model seems to be accurate in obtaining IOP values from the anterior chamber cavity during LASIK. PMID- 17846944 TI - [Persistent corneal defects treated with botulinum toxin-induced ptosis]. AB - OBJECTIVES: To evaluate the use of botulinum toxin (BTX) induced ptosis in the treatment of corneal pathology. METHODS: We employed two BTX injections into the superior lid of 10 eyes (9 patients). We evaluated the degree of ptosis, its duration and the effect on the corneal lesion. RESULTS: Complete ptosis resulted in seven eyes and the corneal pathology resolved in all of them. There were no relevant complications. CONCLUSIONS: BTX treatment is a simple and safe technique for treating refractory corneal pathology. It has significant advantages over surgical tarsorrhaphy and is especially useful where the pathology does not require surgery. PMID- 17846945 TI - [Limbal relaxing incisions and cataract surgery: our experience]. AB - PURPOSE: To evaluate the reduction of pre-existing corneal astigmatism at the time of cataract surgery with limbal relaxing incisions (LRIs). METHODS: A prospective study of two groups of patients (treatment and control) with pre existing astigmatism>or=1D was performed. The 30 patients in the control group had a temporal clear corneal phacoemulsification and the 32 patients of treatment group had combined temporal clear corneal phacoemulsification and LRIs. Holladay analysis was used to assess the efficacy of treatment. An astigmatism distribution and prevalence study in our population is also presented. RESULTS: Three months after surgery, the mean astigmatism change was -0.55D (-0.75 to 0.35) in the treatment group and 0.04D (-0.3 to 0.3) in the control group (p<.0001). CONCLUSIONS: LRI is a simple, safe and effective method not only for reducing pre-existing astigmatism during cataract surgery but in providing good unaided visual acuity. PMID- 17846946 TI - [Adult-onset of recurrent Coats disease]. AB - CASE REPORT: A male diagnosed with Coats disease at the age of 30 years, had a relapse of this condition 14 years later. His first symptom of blurred vision occurred in both episodes and similar findings of unilateral retinal exudation and lipid deposition at boundary were seen. Angiography showed the characteristic early hyperfluorescence of the telangiectasias and late leakage of dye. DISCUSSION: Coats disease is relatively uncommon and, as the degree of involvement varies from case to case, a randomized, prospective study of treatment would probably not be feasible. Despite the characteristic features of this disease, the differential diagnoses must be considered in both children and adults. PMID- 17846947 TI - [Diffuse large B cell lymphoma presenting with a bilateral serous macular detachment]. AB - CLINICAL CASE: A 42 year-old male was assessed for a subacute, bilateral and progressive visual loss. His medical history included chronic hepatitis C infection and Evans syndrome. On fundal examination, multiple areas of neurosensorial and retinal pigmented epithelium detachment were observed in the region of both macula. A few days later, his general health deteriorated and he was noted to have a high fever and adenopathy. Biopsy of an enlarged lateral cervical lymph node demonstrated the existence of a diffuse large B cell lymphoma. After several cycles of chemotherapy, he experienced a progressive and bilateral improvement of his vision, which was accompanied by a reattachment of the previously detached areas. DISCUSSION: A bilateral and serous macular detachment may be the initial manifestation of a diffuse large B cell lymphoma. The prognosis of these retinal lesions may be favourable if lymphoma remission is achieved. PMID- 17846948 TI - [Giant nodular posterior scleritis compatible with ocular sarcoidosis simulating choroidal melanoma]. AB - CASE REPORT: A 30-year-old man was referred to our ocular oncology service with a diagnosis of amelanotic choroidal melanoma of the left eye. The following tests were performed: ophthalmoscopy, fluorescein angiography, indocyanine green angiography, ultrasonography, magnetic resonance imaging and biopsy. DISCUSSION: The diagnosis of giant nodular posterior scleritis, as suggested by ultrasonography, was confirmed by biopsy. A comprehensive medical evaluation was performed, but no etiology was found. The histology revealed a granuloma compatible with ocular sarcoidosis. A rapid response was obtained by systemic steroid administration (1 mg/kg). Sarcoidosis continues to be a challenge in diagnosis. It is important to distinguish nodular posterior scleritis from choroidal melanoma. PMID- 17846949 TI - [Band atrophy of the optic disc secondary to ventricular subependymoma compression]. AB - CASE REPORT: A 42-year-old man was diagnosed with band or "bow tie" optic atrophy with a right homonymous hemianopia. Computerized tomography (CT) revealed a calcified lesion in the left hippocampus. Craniotomy and tumor resection were performed. The biopsy revealed a subependymoma of the temporal horn of the left ventricular system. DISCUSSION: Optic tract lesions are uncommon clinical entities, in which homonymous hemianopia and contralateral band optic atrophy are characteristic. Subependymomas are infrequent and benign tumors that are typically associated with the ventricular system. PMID- 17846950 TI - [Amniotic membrane transplantation with fibrin glue as treatment of refractory conjunctivochalasis]. AB - CASE REPORT: A 63-year-old man with bilateral conjunctivochalasis presented with tearing, irritation, foreign body sensation and a delayed fluorescein clearance test. After no symptomatic improvement with topical treatment, surgery was carried out, with amniotic membrane transplantation and fibrin sealant. DISCUSSION: Conjunctivochalasis is a frequent disorder that shares symptoms with dry eye syndrome. When there is no response to topical treatment, surgical treatment is needed. The surgical technique described by Tseng, and based on amniotic membrane transplantation without suture, resulted in a very useful response, due to less inflammation and a rapid resolution and improvement of symptoms. PMID- 17846951 TI - [Eclipse retinopathy: three case reports]. AB - CASE REPORT: We present the evolution of eclipse retinopathy in 3 patients who came to our hospital after the eclipse of October 2005 and had foveal lesions and visual field alterations. DISCUSSION: Eclipse retinopathy is a maculopathy that occurs after exposure to intense solar radiation, such as occurs during an eclipse, and is produced by a photochemical mechanism. Although the macular changes and symptoms are usually reversible, residual defects at the level of the EPR and scotoma in visual fields can occur. For these reasons the most appropriate treatment is prevention by means of public awareness campaigns. PMID- 17846952 TI - [Acute retinal necrosis syndrome following chickenpox]. AB - CASE REPORT: A 34-year-old male patient developed acute retinal necrosis in his left eye about three weeks after the onset of chickenpox. Systemic antiviral treatment with intravenous acyclovir (10 mg/kg/8 hours) and systemic corticosteroids (1 mg/kg/day) controlled the retinitis and the patient suffered no loss of visual acuity. DISCUSSION: Acute retinal necrosis is an unusual complication of chickenpox. A mild form of this entity has been described during the course of primary varicella-zoster infection. Adequate and early therapy during the acute phase of the disease with intravenous acyclovir and systemic corticosteroids is recommended to achieve a satisfactory visual acuity and prevent complications. PMID- 17846953 TI - [Simultaneous botulism in two brothers addicted to cocaine]. AB - INTRODUCTION: Botulism is currently an uncommon disease in which the botulinum toxin causes a progressive muscular paralysis that can lead to the death due to a failure of respiratory muscles. CLINICAL CASE: Two brothers, both addicted to cocaine, came to the casualty department because of a decrease of near visual acuity and bilateral mydriasis. Two days later, they developed eyelid ptosis, asymmetric dysfunction of the extraocular muscles and vomiting. DISCUSSION: The presence of a paralysis of accommodation, with bilateral mydriasis that reacts to pilocarpine, makes it necessary to consider botulism as a possible cause. PMID- 17846954 TI - [Possible recurrent multiple evanescent white dot syndrome and chroroidal neovascularization]. AB - CASE REPORT: We present an unusual case of recurrent and bilateral multiple evanescent white dot syndrome (MEWDS), who had three bilateral episodes in a period of nine years. Thirteen years after the first episode, she was diagnosed with subretinal neovascularization (SRNV) which showed a satisfactory response to photodynamic therapy, with a final visual acuity of 20/40. DISCUSSION: MEWDS is considered classically to be an inflammatory disease with a good visual prognosis. Although the development of SRNV is unusual, we recommend long term follow-up of these patients since the early diagnosis and treatment of SRNV are both relevant for the retention of visual acuity. PMID- 17846955 TI - [The 16th Assembly of the Spanish Society of Hispanic American Ophthalmology]. PMID- 17846956 TI - [Posters from the civil war]. PMID- 17846957 TI - [Central retinal vein occlusion]. PMID- 17846958 TI - [Cross linking]. PMID- 17846959 TI - [Therapeutic cross-linking of the cornea using riboflavin/UVA]. AB - BACKGROUND: The method of cross-linking of the cornea using riboflavin and ultraviolet light (UV) has recently entered the phase of clinical evaluation. The purpose of this paper is to review the current knowledge about corneal cross linking. METHODS: A literature research (medline) using the key words "cross linking" and "cornea" revealed 99 citations. Thirty-four of the 99 articles dealt with the topic and were used for this review. Some of our own as yet unpublished data were also included. RESULTS: In a first phase (until 2003) different methods of cross-linking were experimentally compared regarding efficacy and safety. As the most promising compromise the use of UVA (370 nm) and riboflavin as a photomediator was tested in pilot studies on human eyes with progressive keratoconus. In 2003, the first results of such pilot studies were published. Surprisingly, not only a halt in progression was found but in more than half of the eyes treated a regression towards a more regular cornea took place. So far, no complications have been reported. Keratocytes are killed up to 320 microns deep in the stroma and the endothelium appears unaffected. Nine cases of therapy refractory corneal melting were treated by means of UVA/riboflavin cross-linking and in 8 of the 9 cases the melting process was stopped. CONCLUSIONS: In the current situation, we can state only that UVA/riboflavin cross-linking of the keratoconus cornea leads in the majority of the cases to a halt of the progression and complications seem to be rare. There are not yet enough data available to establish a list of indications and contraindications. A potential clinical acceptance of the procedure requires the results of prospective controlled studies that are currently underway. PMID- 17846960 TI - [Scope and limititions of innovative vitrectomy systems]. AB - PURPOSE: The aim of the present article is to review the methodical and technological development of pars plana vitrectomy. Special attention is drawn to safety, efficiency and functionality of the innovative 25-gauge und 23-gauge vitrectomy systems which are compared to the standard 20-gauge vitrectomy system. This was done based on clinical studies and case reports. METHODS: A literature search was conducted in a cluster of different medical databases (XMedall; XPharmall). Focus of the research was the "development" and "status quo" of pars plana vitrectomy. In particular, clinical studies and case reports dealing with safety and efficiency of 20-, 23- and 25-gauge vitrectomy systems have been evaluated. Only peer-reviewed articles from 1966 until today were investigated. Finally, a descriptive analysis of the relevant studies was made. RESULTS: Both innovative vitrectomy systems are safe and effective and help to reduce operating time. There was no significant difference in postoperative complications following 25-gauge vitrectomy and 20-gauge vitrectomy. 25-gauge instruments, however, show a greater flexibility. For this reason a certain learning curve is required and the range of application is limited. Due to its greater stiffness and larger diameter, the 23-gauge system - while still allowing a transconjunctival access - may overcome the disadvantages of the 25-gauge system. However, the use of silicone oil may lead to leakage of the sclerotomies and thus necessitate additional suturing. CONCLUSION: The use of both innovative vitrectomy systems offers the advantage of a faster and less invasive surgical procedure. However, there are disadvantages which limit the indications for 25 gauge vitrectomy. The 23-gauge vitrectomy may overcome these disadvantages and - due to its wider range of application - may be used instead of conventional 20 gauge vitrectomy in most cases. It may therefore become the new standard for vitrectomy. PMID- 17846961 TI - [Intact accommodation in pseudophakic eyes]. AB - BACKGROUND: The purpose of the cataract surgery should be to guarantee the physiology of a young eye, especially with the ability to accommodate. This study focuses on accommodative changes in pseudophakic eyes. MATERIALS AND METHODS: Using the IOL Master (Carl Zeiss Jena), Scheimpflug camera EAS 1000 (Nidek) and Pupillograph (AMTech GmbH), detailed measurements of pseudophakic eyes for near and distance fixation were taken. The average age of all patients is 71 years. RESULTS: With regard to the pseudophakic pupil movement a statistically significant decrease of the pupil size, for the light-influenced, and for the light-constricted pupil in near fixation could be shown. Furthermore, a statistically significant decrease of the pupil-constricting amplitude and a decrease of the reaction time after a light impulse was shown. Central vertical and horizontal corneal radii show significant increases with accommodation, which results in a decrease of the central corneal curvature. While reducing the anterior chamber depth, the pseudophakic eyes show a statistically significant minimising of the superior anterior chamber angle. CONCLUSION: Pseudophakic accommodating eyes react similarly compared to the phakic accommodating eyes of young individuals. PMID- 17846962 TI - [Comparing applanation and impression tonometry in Central African Bantu people]. AB - BACKGROUND: Glaucoma is the main reason for irreversible blindness in the Central African population. Because of the high prevalence, the rapid progression and the limited possibilities of diagnosis and treatment in Africa, glaucoma leads more often to blindness, compared with other parts of the world. The irreversible character of the glaucoma makes it necessary to recognise this disease as soon as possible. Beside the appearance of the optic nerve and visual field defects, tonometry is considered as an essential part of the diagnosis of glaucoma. This study compares the Shiotz tonometer with applanation tonometry to find out whether the Shiotz tonometer presents similar results in the African population. STUDY DESIGN: In the time between October 2001 and July 2002 in the Democratic Republic of Congo 2020 eyes of 1027 persons were examined. Beside other ophthalmological examinations the intraocular pressure were taken by applanation (Perkins tonometer) and impression tonometry (Shiotz tonometer). RESULTS: A difference of more than 2 mmHg between the two methods was found in 26.5 % of the examined eyes. Among the first 1000 eyes this difference was found in 40 % of the eyes, while among the second part of the examined eyes only in 13.2 % did a difference appear. Both methods showed a good correlation with k = 0.96 (p < 0.01). For short- or long-sighted eyes, a difference between both methods was found more often than for normal eyes. Among the long-sighted eyes the impression tonometry found higher values for the intraocular pressure more often than among the short-sighted eyes. But altogether the applanation tonometry showed higher values more often for short- as well as for long-sighted eyes. There were no correlations between the age of the examined persons and the difference between the two methods. CONCLUSION: Altogether it can be said that for screening impression tonometry shows a satisfactory correlation with applanation tonometry in the hands of a well-trained ophthalmologist, who has done at least 1000 examinations. Differences between the two methods are mainly found for long- or short-sighted eyes. PMID- 17846963 TI - [Cost-utility analysis of ranibizumab (Lucentis) in neovascular macular degeneration]. AB - PURPOSE: Ranibizumab (Lucentis) stabilizes or improves visual acuity in a high percentage of patients with age-related macular degeneration (AMD). As this therapy is associated with significant costs, the aim of this study was to provide a cost-utility analysis, which considers both costs and utility of a therapy with ranibizumab in an economic model. METHODS: The incremental utility for the patient was modelled based on visual acuity data of the MARINA and ANCHOR study. The utility data used assume that the better seeing eye is affected. The study groups used for comparison consisted of patients who only received best supportive care, e. g., low-vision aids. The baseline scenario of the model assumes 6 treatments per year over a 2 year time period - based on the assessment of an expert panel. Treatment costs were based on German pharmacy prices and recommendations for reimbursement of the intravitreal injections. In a univariate sensitivity analysis all important parameters were varied to assess the stability of the results. RESULTS: The baseline scenario yields for predominantly classic lesions 16,882 euro/QALY (quality adjusted life year), for minimally classic CNV 24,766 euro/QALY and for occult CNV 26,170 euro/QALY. If a distribution of the CNV types with 18 - 25 - 57 % is assumed, the mean cost of therapy with ranibizumab amounts to 24,147 euro/QALY. Sensitivity analysis showed that all reasonable variations yielded results which are considered cost-effective ( 0.4) visual acuity, for a variation of costs per treatment of +/- 20 %, and a prolonged treatment duration of 3 years. CONCLUSIONS: In the investigated szenario a therapy of neovascular AMD with ranibizumab is cost-effective for all angiographic subtypes as well as in the sensitivity analysis. PMID- 17846965 TI - [Hematocornea]. PMID- 17846964 TI - [Recurrent corneal tumour in a child]. AB - We present the clinical and histopathological findings in the unusual case of a recurrent corneal tumour in a child. Light and ultrastructural observations as well as immunohistochemistry indicate a benign reactive process. However, the prognosis regarding visual function is poor due to the infiltrative nature of the lesion and its tendency to recur. A possible diagnosis of nodular fasciitis is discussed. PMID- 17846966 TI - [A case of protracted, bilateral angle closure glaukoma, masked by fentanyl]. PMID- 17846967 TI - The challenge of the Metabolic Syndrome. PMID- 17846968 TI - The future of metabolic syndrome and cardiovascular disease prevention: polyhype or polyhope? Tales from the polyera. AB - Recently society has been witnessing the rise of a new era in the prevention and treatment of the metabolic syndrome and cardiovascular disease: the Polyera. This new era started when a promising concept - the Polypill - was introduced by Wald et al. in 2003. The Polypill is a theoretical combination of six pharmacological compounds (a statin, three different antihypertensives, aspirin, and folic acid) that in combination could reduce cardiovascular disease by more than 80%. Although the Polypill could theoretically be a highly effective intervention, it is not yet available in the market and its effectiveness remains unproven. In the population at large, cheap prizes may come at prohibitive costs. With frail elderly and population prevalences of co-morbidity far higher than in drug trials, rare adverse effects may be frequent. In December 2004, a more natural, safer, and probably tastier alternative to the Polypill - the Polymeal - was introduced. Contrary to the Polypill, the Polymeal combined 6 different foods (fruits and vegetables, almonds, chocolate, wine, fish, and garlic) that taken together in a regular basis could cut cardiovascular disease risk by over 75%. Polyproducts from the polyera in true populations might hide unexpected polyinteractions. In the polyera, polytrials will need to establish benefits, harms, and costs. PMID- 17846969 TI - Comparison of the prevalence of the metabolic syndrome by WHO, AHA/NHLBI, and IDF definitions in a German population with type 2 diabetes: the Diabetes in Germany (DIG) Study. AB - This study investigated the prevalence of the metabolic syndrome (MetS) in a German population with type 2 diabetes (T2DM) using the three definitions for MetS according to WHO 1999, AHA/NHLBI 2005, and IDF 2005 criteria. Four-thousand and twenty participants as a cross section of daily practice of diabetes care in Germany (238 unselected sites) were included in the Diabetes in Germany (DIG) study. INCLUSION CRITERIA: T2DM and age between 35-80 years. EXCLUSION CRITERIA: major cardiovascular event < 3 months before entry, NYHA-IV, macroproteinuria, and cancer < 5 years before entry. The components of MetS were measured following a standard protocol for anthropometric and laboratory control. The average diabetes duration was 8.4 years and HbA (1C) 7.0%. The prevalence of MetS by WHO criteria was 26.1%, by AHA/NHLBI 79.3%, and by IDF 82.6%. The degree of agreement (kappa statistic) was kappa = 0.69 between AHA/NHLBI and IDF definitions, but only 0.12 for WHO VS. IDF, and 0.17 for WHO vs. AHA/NHLBI. The frequency of central obesity by WHO was 50.9%, by AHA/NHLBI 72.9%, and by IDF 92.0% and for hypertension 29.3%, 92.6%, and 92.6%, respectively. However, the frequencies of lipid components by the three definitions were in the same range (57.8%, 59.5%, 59.5%). In this representative German sample of patients with type 2 diabetes, the prevalence of MetS was very highly independent of using the IDF or AHA/NHLBI definition. Females were significantly more affected than males. The distinctly lower prevalence delineated from WHO criteria is due to low frequency of central obesity and hypertension as consequence of higher cutoff limits for these components used in the WHO definition. PMID- 17846970 TI - Prevention of type 2 diabetes--lessons we have learnt for implementation. AB - The challenge today is to implement successful diabetes prevention programs in general health care. Even if not all questions for the prevention of diabetes are answered, we have today overwhelming evidence that diabetes can be prevented or delayed in high risk population through lifestyle modification or pharmacological interventions. This information has to be translated now into well-defined strategies for screening and treating high risk population in daily practice. It is necessary then to develop and implement prevention programs into clinical practice considering scientific aspects and practical requirements during implementation. While translating the scientific evidence into population based intervention strategies more and more questions arise, mostly related to economic and structural requirements during implementation. At the end, giving the right answers to these questions will decide about the success of implemented prevention strategies. Here, we will try to answer some of the questions which arose during the implementation of a prevention management concept into clinical practice. We focus on the development of a structured prevention management program which will enable implementation of diabetes prevention into clinical practice. PMID- 17846971 TI - The metabolic syndrome and risk of cardiovascular disease and diabetes: experiences with the new diagnostic criteria from the International Diabetes Federation. AB - Since the publication of the International Diabetes Federation (IDF) consensus definition of the metabolic syndrome (MetS) in 2005, numerous studies have compared the new IDF MetS category with previous MetS definitions in its association with the prevalence of cardiovascular disease, and in its ability to predict vascular events and incident diabetes. The present review shows that the amount of cardiovascular risk conferred by the respective MetS definitions varies between populations; in most populations it is lower with the IDF MetS than with alternative MetS definitions. For incident diabetes, the number of existing studies appears too limited to draw definite conclusions. Like earlier definitions of the MetS, the IDF MetS is based on distinctive cutoff points for MetS stigmata, neglecting the fact that the risk factors are continuous and not categorical variables. PMID- 17846972 TI - Metabolic syndrome risk in black South African women compared to Caucasian women. AB - Rapid urbanisation has led African women to have an obesity prevalence double than that of Caucasian women, and this also holds true for the stroke prevalence in Africans. The study aimed to compare various metabolic syndrome (MS) criteria of the International Diabetes Federation (IDF) of body mass index and age-matched African (n=102) and Caucasian women (n=115). More Caucasian (30.4%) than African women (24.8%) had MS. Only 48% of African women had waist circumferences (WC) higher than the IDF cutoff, compared to 62.6% of Caucasians. Caucasian women were significantly taller and heavier and had higher triglycerides, plasminogen activator inhibitor-1 activity, and cortisol. African women had significantly higher blood pressure, leptin, fibrinogen and C-reactive protein, and higher odds ratios for having the MS for HDL-cholesterol, blood pressure, and fasting glucose than Caucasians. It is concluded that the IDF WC criterion needs a downward adjustment for African women due to a smaller body size. Lean African women seem to be at higher risk for MS than Caucasians. South Africa needs to stem the increasing rates of type 2 diabetes by decreasing obesity and by education (unschooled African women showed a 4.8 times higher likelihood of having MS than schooled women). PMID- 17846973 TI - Emerging role of SUMO in pancreatic beta-cells. AB - Post-translational attachment of small ubiquitin-like modifier (SUMO), defined as SUMOylation, can affect the localization, interactions, stability and/or activity of substrate proteins, and thus can participate in a large variety of cellular processes. Most SUMO substrates are involved in transcriptional regulation. Hence, SUMOylation can either activate or, more commonly, repress gene transcription. The modulation of gene expression by SUMO through diverse mechanisms and specifically the recent findings concerning SUMOylation in pancreatic beta-cells are reviewed. PMID- 17846974 TI - Improved vascular function upon pioglitazone treatment in type 2 diabetes is not associated with changes in mononuclear NF-kappaB binding activity. AB - Thiazolidinediones such as pioglitazone have been shown to exert anti inflammatory effects independent of their insulin sensitizing effects by reducing activation of the proinflammatory transcription factor NF-kappaB in animal models of experimental diabetes. Furthermore, short-term pioglitazone treatment ameliorates endothelial dysfunction in conduit arteries of patients with type 2 diabetes. Since inflammation is supposed to impair flow-mediated vasodilatation, we studied the effects of an 8-week pioglitazone intervention on endothelial function and mononuclear NF-kappaB activation in patients with type 2 diabetes. Twenty patients were included in a randomized, double-blind, placebo-controlled study receiving 30 mg pioglitazone or placebo, respectively. Flow-mediated endothelium dependent vasodilatation (FMD) of the brachial artery, NF-kappaB binding activity in peripheral blood mononuclear cells [pBMC, determined by electrophoretic mobility shift assay (EMSA)] and interleukin-6 (IL-6) transcription rates (determined by real-time PCR) were measured at study entry and after eight weeks of intervention. Pioglitazone treatment resulted in a significant improvement of FMD (4.3%+/-3.3; p=0.003), while no effect was seen under placebo medication (2.0%+/-2.7; p=0.71). The correction of FMD was neither paralleled by a pioglitazone-dependent reduction in mononuclear NF-kappaB binding activity (DeltaNF-kappaB activity: pioglitazone: 9.2%+/-6.7, p=0.24; placebo: 5.7%+/-19.6; p=0.82) nor in NF-kappaB dependent gene transcription as determined for IL-6 (DeltaIL-6 pioglitazone: +1.8%+/-12.0, p=0.93; placebo: -0.2%+/-9.7; p=0.92). These data demonstrate for the first time that pioglitazone treatment improves endothelial dysfunction in patients with type 2 diabetes without affecting NF-kappaB binding activity and NF-kappaB dependent proinflammatory gene expression in pBMC. PMID- 17846975 TI - Apoptosis in patients with dilated cardiomyopathy and diabetes: a feature of diabetic cardiomyopathy? AB - BACKGROUND: Dilated cardiomyopathy (DCM) has been suggested to be a consequence of a prior viral infection leading to a chronic inflammatory and immunological reaction that leads to a structural and functional deterioration of the heart. Nevertheless, the results of present studies are conflicting, regarding the natural course of heart diseases associated with detection of viral genome and inflammation. On the other hand, diabetes mellitus (DM) is the leading endocrine disorder worldwide and sufficient to induce a cardiomyopathy. It is not known whether DM contributes to the clinical picture of cardiomyopathy associated with the presence of viral genome or inflammatory cells in the myocardium. Therefore, the present study was undertaken to compare histological, immunohistochemical, biochemical, and functional data as well as the outcome of patients presenting with DCM and positive for DM with patients negative for DM to evaluate for a diabetic contribution in the course of the disease. METHODS: A total of 216 patients were biopsied between January 1998 and April 2003. From 197 patients diagnosed as having DCM, we were able to complete data set regarding the presence of DM in 108 patients, 20 patients with and 88 patients without DM. RESULTS: There was no significant difference regarding age, gender, body mass index, presence of viral genome and inflammatory cells in the myocardium, left ventricular function and diameter, and the degree of heart insufficiency. There was a significant difference of apoptotic cells in the myocardium of patients with DCM and DM compared to patients with DCM alone (1.7+/-1.9 vs. 0.2+/-0.4, p=0.028). During the follow-up of 16 months, left ventricular function improved in both groups significantly, but not between the groups. Death or transplantation-free survival was not significantly different. CONCLUSION: The different findings regarding the presence of apoptotic cells suggest a contribution of pathobiological pathways in the patients with DM to the underlying heart disease. PMID- 17846976 TI - A simplified Finnish diabetes risk score to predict type 2 diabetes risk and disease evolution in a German population. AB - AIMS: The FINDRISC questionnaire is a screening tool to estimate the risks for type 2 diabetes as well as asymptomatic type 2 diabetes. We aimed to evaluate its performance to predict diabetes in a German population and to compare its predictive and detective ability in the same population. METHODS: A total of 552 subjects with increased risk of type 2 diabetes were investigated. All individuals completed the FINDRISC questionnaires and underwent an oral glucose tolerance test (OGTT). All individuals were followed for 3 years and underwent an OGTT again. The performance of the opportunistic screening was assessed with the area under the receiver operating characteristics curve (AUC). An intervention program was carried out for all diabetic and IFG/IGT patients at baseline. RESULTS: For identification, the asymptomatic type 2 DM was named Condition 1; prediction of type 2 DM risk in the follow-up survey as Condition 2; and diabetes risk predicting in a hypothetical case of survey without intervention program as Condition 3. The ROC-AUC in the three condition were AUC (FINDRISC1)=0.745, AUC (FINDRISC2)=0.789, and AUC (FINDRISC3)=0.775, respectively. A significant association between FINDRISC and evolution of disease was found, but the variation of plasma glucose during the three years follow-up was not associated with FINDRISC. People in the intervention group with an improvement of glucose tolerance had a smaller FINDRISC score than persons with an unchanged or progressive condition of disease. CONCLUSION: FINDRISC was validated in our study as a simple tool with high performance to predict diabetes risk and less efficient to identify asymptomatic type 2 diabetes. People with lower FINDRISC score will benefit easier from preventive intervention. PMID- 17846977 TI - Acute glucose fluctuations and chronic sustained hyperglycemia as risk factors for cardiovascular diseases in patients with type 2 diabetes. AB - Chronic hyperglycemia, usually assessed from HbA1c determinations, results in excessive glycation and generation of oxidative stress. As a consequence, chronic hyperglycemia has been identified as a risk factor for diabetes complications leading to accelerated atherosclerosis. Both fasting and postprandial hyperglycemia contribute to this process. However the acute glucose fluctuations that occur in diabetes have been recently described as an additional factor that activates the oxidative stress. As a consequence, acute glucose swings, including upward (postprandial) and downward (interprandial) fluctuations can be considered as risk factors for cardiovascular events and should be included in the "dysglycemia" of diabetes in combination with fasting and postprandial hyperglycemia. As postprandial glucose is a contributor of both acute glucose fluctuations and chronic sustained hyperglycemia, it remains difficult to know whether these 2 mechanisms are equivalent or not equivalent risk factors for cardiovascular disease. PMID- 17846978 TI - The importance and effect of dietary fiber in diabetes prevention with particular consideration of whole grain products. AB - The state of prediabetes is characterized by an increase in insulin resistance and a decrease in pancreatic beta cell function. The prestage of type 2 diabetes mellitus can be identified by an impaired glucose tolerance and/or by an impaired fasting blood sugar. Apart from weight loss and increase in physical activity, the development of type 2 diabetes mellitus can also be prevented by dietary changes. A low-fat diet with a dietary fiber intake of more than 30g/d was shown to represent an effective preventive approach. A high-fiber diet has many positive effects on the physical health status. In addition to positive effects in the gastrointestinal tract it has an obvious potential to support weight reduction and to improve disturbances of carbohydrate and fat metabolism. At the present state of knowledge, insoluble dietary fibers as found in whole grain cereal products are considered to be especially effective in the prevention of type 2 diabetes mellitus. A high intake of fruits and vegetables as well as pulses also exerts health-promoting properties. A high-fiber diet also plays an important role in the prevention of obesity and coronary heart diseases. PMID- 17846979 TI - Moderate weight loss reduces renin and aldosterone but does not influence basal or stimulated pituitary-adrenal axis function. AB - Body fat mass and nutrition influence secretion of the adrenocortical hormones- aldosterone and cortisol--via several mechanisms. However, there are no data on adrenocortical function following widely prescribed mild diet-induced weight loss (10%) in obese subjects. In the present study, 25 healthy obese volunteers (BMI 32.9+/-4.3 kg/m (2)) followed a 30% calorie restricted diet over 12 weeks. Hypothalamic-pituitary-adrenal (HPA) axis function was assessed by 24-hour urine free cortisol/cortisone and a 1 mcg ACTH stimulation test with measurement of total and free cortisol and corticosteroid-binding globulin (CBG). The renin angiotensin-aldosterone system (RAAS) was assessed by measurement of plasma aldosterone and renin under salt depleted (30 mmol/d) and loading (250 mmol/d) conditions. Volunteers' weight fell by 8.5+/-0.8 kg (8.9+/-0.7%) and seated systolic blood pressure fell by 8.7+/-2.7 mmHg and diastolic blood pressure by 7.0+/-1.4 mmHg (p<0.01). Plasma aldosterone and renin levels fell significantly with weight loss (aldosterone: 853+/-156-635+/-73 pmol/l; renin: 35.4+/-7-24+/-3 mU/l, both p<0.05). The volunteers were relatively salt insensitive (mean arterial pressure change with salt intake: 4 mmHg) and this was not affected by weight loss. Moderate weight loss had no effect on 24-hour urine free cortisol/cortisone, or on basal, or ACTH-stimulated free and total cortisol, or CBG. Hence this conventional weight loss program reduces blood pressure and activity of the RAAS via an effect on renin release. Despite various described influences of fat mass and energy restriction on HPA axis function, there were no changes in basal and stimulated HPA axis function with moderate weight loss. There may be a threshold effect of weight loss/energy restriction required to alter HPA axis function, or moderate weight loss may lead to a counterbalanced effect of stimulatory and inhibitory influences on HPA axis function. PMID- 17846980 TI - High prevalence of dyslipidemia in the Dresden Jewish population. PMID- 17846981 TI - Increased prevalence of thyroid disease in emigrants of the former Soviet Union: is the hypothalamus-pituitary-adrenal (HPA) axis involved? PMID- 17846982 TI - Unregistered subtracted CT angiography for the visualization of intracranial arteries at or near the skull base: preliminary experience. AB - PURPOSE: Restrictions with computed tomography angiography (CTA) regarding the visualization of arteries near the skull base are well known. Today, the gold standard for overcoming this is the matched mask bone elimination method. Worldwide use of this method is limited since it requires advanced imaging physics and software. A more simple method was introduced recently that avoided motion artifacts significantly by restraining the patient's head with a vacuum type head holder. The purpose of this study was to investigate the feasibility of using unregistered subtracted CTA without such head-holding methods. MATERIALS AND METHODS: Of the 42 patients that underwent subtracted CTA, 39 were recruited for this study. Two patients were excluded due to agitation during examination and one due to artifacts of an embolized aneurysm. All the examinations were performed in an 8-channel multidetector CT suite. After performing a non-contrast low-dose CT examination, CTA was carried out using the same scan planes as on the scout images. Images were transferred to a workstation and subtraction was performed. Hard-copy images through identical locations were reviewed by 2 observers, a radiologist and a clinician (neurologist), and visualization of the internal carotid artery and posterior artery systems were scored. Data were analyzed using the Wilcoxon signed-rank test. RESULTS: Significant statistical differences, in favor of subtracted images, were noted in both observers' scores, both for the internal carotid artery and posterior system arteries. The differences in the clinician's scores were more prominent than that of radiologist's. CONCLUSION: These results are promising for the expanded use of the subtraction method, especially in radiology departments that lack the staff and equipment for registered methods. PMID- 17846983 TI - Neuro-otologic applications of MRI. AB - Magnetic resonance imaging (MRI) has increasingly new applications in neuro otology. The aim of this review was to summarize MRI applications in neuro- otology and make a correlation between neuro-otologic anatomy and MR images. Different MRI techniques have been described in the imaging of different neuro otologic structures. In particular, we discuss the effectiveness, indications, and techniques of MRI in the demonstration of neuro-otologic tracts and their related pathologies. MRI should be the first choice imaging modality for the evaluation of retrocochlear pathologies. PMID- 17846984 TI - Osmotic demyelination syndrome in a 40-day-old infant. AB - Osmotic demyelination syndrome refers to the myelin destruction of various brain structures that follows osmotic stress. It affects myelinated brain; therefore, it is very rare in babies and it has not been reported in patients younger than 10 months of age. Herein, we present a 40-day-old infant with osmotic demyelination syndrome, along with imaging findings. Her pontine and thalamic lesions regressed during the 10-day treatment course, whereas demyelinated areas in the lentiform nucleus persisted. Magnetic resonance spectroscopy of the latter revealed decreased levels of all major metabolites. Imaging findings remained unchanged after that phase. PMID- 17846985 TI - Differentiation of cytotoxic and vasogenic edema in a patient with reversible posterior leukoencephalopathy syndrome using diffusion-weighted MRI. AB - In recent years reversible posterior leukoencephalopathy syndrome (RPLS) has become increasingly recognized. It represents an uncommon entity related to multiple pathologies, the most common being hypertensive crisis. The underlying pathophysiological mechanism is proposed to be one of vasogenic edema, without infarction; however, differentiation from cytotoxic edema can be crucial for therapeutic and clinical outcome. Diffusion-weighted magnetic resonance imaging (DWI), including calculation of the apparent diffusion coefficient (ADC), may be helpful for differentiation. We present a case of a healthy young woman in the 40th week of gestation, with no prior complications, who suddenly developed RPLS with vasogenic edema, which was differentiated with DWI and quantification of ADC. Follow-up cranial MRI showed complete remission. Pre-eclampsia could not be proven according to pathognomonic laboratory findings. PMID- 17846986 TI - Mammography device use in Turkey, and quantity and quality analysis of mammography education. AB - PURPOSE: To evaluate in detail the ways and methods of mammography education, to survey currently used mammography devices, and to determine the quality of mammography examinations in Turkey in order to increase the quality of said examinations and to offer guidance to standardization studies in Turkey. MATERIALS AND METHODS: This study depended on the analysis of a questionnaire that was completed by volunteering medical centers. The questionnaire was mailed to all institutions in Turkey with a mammography device and which were registered with the Turkish Atomic Energy Commission and individual city health administration databases (n = 456). RESULTS: It was not possible to determine the exact number of mammography devices in Turkey. In all, 270 questionnaires were completed and returned from the registered centers. Among the mammography devices declared (n = 291), automatic exposure control (AEC), spot view, and magnification view were not used at 21%, 34%, and 43% of the centers, respectively. Preoperative wire localization was not practiced at 180 centers (62%) despite the ability to do so. At 16% of the centers, mammograms were not labeled and at 57% of the centers labeling was handwritten. At 23% of the centers only small cassettes were used, and at 58% the heat and at 94% the humidity of film storage areas were inappropriate or unknown. At 25% of the centers light and at 15% radiation exposure of the film was present. Mammography quality control tests were performed at 40%, and in 70% control records were not well kept. There were no thermometers in 49% of the centers, no phantom breast at 80%, no sensitometer at 93%, and no densitometer at 81%. At 50% of the centers, regular periodic maintenance was not performed. Second look was performed consistently at 12% of the centers and BI-RADS (Breast Imaging Reporting and Data System) categorization was used at 40%. CONCLUSION: The exact number of mammography devices is not officially known in Turkey, and it is apparent that registration of some devices was not made by the Turkish Atomic Energy Commission. Questionnaire responses about mammography education and procedures revealed that there was a serious lack of quality across regions. Education, accreditation, inspection, and sanctions are needed immediately to institute standardization and improve quality. This is a critical situation that should be addressed by the Turkish Society of Radiology. PMID- 17846987 TI - Clinical evaluation of breast dose and the factors affecting breast dose in screen-film mammography. AB - PURPOSE: To investigate the factors affecting the mammographic breast dose. MATERIALS AND METHODS: The assessment was done on 622 qualified mammograms obtained with use of "variable kV" technique, i. e., semiautomatic mode, in screen-film mammography. Actual breast doses were calculated and analyzed to determine the roles of two screens and three films, two anode/filter selections (Mo/Mo and Mo/ Rh), three imaging projections (craniocaudal, 45 degrees and 60 degrees mediolateral oblique [MLO]), breast thickness, and breast composition. RESULTS: Min R 2190 screen provided about half dose of Min R screen. All films used with the faster screen resulted in similar doses in < 50 mm thicknesses (mean, 0.9-1.1 mGy) (P > 0.05). The doses were significantly greater in thicker (> or =50 mm) breasts, in dense breasts, and in 45 degrees MLO view, compared to the < 50 mm breasts, fatty breasts and in 60 degrees view (P < 0.05). CONCLUSION: The affecting factors of dose are many, and their complex interrelations are difficult to control in clinical settings. Well tailoring of kVp/anode/filter combination, selection of faster screens and well matched films are mandatory, while 60 degrees instead of 45 degrees in oblique projection can help reducing the dose. However, tailoring of kVp/anode/filter, which should be based on both breast thickness and composition, is difficult to achieve accurately at all times. Therefore, automatic beam quality control should replace the semiautomatic mode in screen-film mammography practice in order to provide easier and more effective control on breast dose and image quality. PMID- 17846988 TI - Leiomyosarcoma of the inferior vena cava. AB - Primary vascular leiomyosarcoma is a rare tumor, which arises mainly from the inferior vena cava. Clinical signs are non-specific. Systemic metastasis occurs in the late stage. Imaging with color Doppler ultrasonography, contrast-enhanced computed tomography, or magnetic resonance imaging can significantly contribute to the diagnosis. We present a case of leiomyosarcoma of the inferior vena cava that extended into the right renal vein and the right iliac vein, as it is a rare case and emphasize the significance of the imaging methods in its diagnosis. PMID- 17846989 TI - CT measurement of trunk muscle areas in patients with chronic low back pain. AB - PURPOSE: The objective of this study was to determine the cross-sectional area changes of the paraspinal, isolated multifidus, quadratus lumborum, psoas, and the gluteus maximus muscles with CT in patients with chronic low back pain. MATERIALS AND METHODS: In this study, we evaluated 36 patients with chronic low back pain and 34 healthy volunteers. The mean age of the patients was 43.2 +/- 6.9 years (range, 30- 58 years) and the mean age of control group was 44.4 +/- 6.9 years (range, 31-61 years). We defined pain that lasts more then one year as chronic pain. Female patients were selected for standardization. All patients were housewives. None of the patients or controls engaged in physical activity other than routine housework. We used a visual analog scale and the Oswestry Pain Questionnaire for clinical evaluation. We made CT cross-sections of the paraspinal muscles at the upper and lower endplates of L4, and of the gluteus maximus at the head of the interfoveal level. RESULTS: In the patient group the multifidus, psoas, and quadratus lumborum cross-sectional areas were smaller than in the control group, and the P values were P = 0.002, P = 0.042, and P = 0.047, respectively, at the L4 endplate. At the L4 endplate level, cross-sectional areas of the multifidus and paravertebral muscles in the patient group were smaller than in the control group, and the difference was statistically significant (P = 0.001, P = 0.010, respectively). We did not find any significant difference between the patient and the control groups in gluteus maximus cross-sectional area. CONCLUSION: Chronic low back pain caused atrophy of the paraspinal, isolated multifidus, quadratus lumborum, psoas, and the gluteus maximus muscles to varying degrees, which was most prominent in the multifidus. Atrophy was noted in all of the studied muscles, except the gluteus maximus. The reliability of CT in measuring the cross-sectional areas of the back muscles was acceptable. PMID- 17846990 TI - Idiopathic bilateral acetabular labral ossification. AB - Acetabular labral ossification is an uncommon condition. We present a case of bilateral idiopathic acetabular labral ossification with no predisposing factor. The differential diagnosis of its plain radiographic appearance is discussed. PMID- 17846991 TI - Ultrasonographic diagnosis of iliac vein compression (May-Thurner) syndrome. AB - Iliac vein compression syndrome (IVCS), also known as May-Thurner syndrome, is the result of compression of the left common iliac vein between the right common iliac artery and overlying vertebrae. The most common clinical presentation is left lower extremity deep vein thrombosis. Rarely, a patient with IVCS can present with obstruction of venous outflow, without deep vein thrombosis. Iliac vein compression, with or without thrombosis, should be treated if symptomatic. We present a patient with IVCS that was initially diagnosed with transabdominal ultrasonography (US), and then confirmed with computed tomography and venography with pressure measurements. We believe this is the first report of an IVCS patient diagnosed with US. PMID- 17846992 TI - Endovenous laser ablation for saphenous vein insufficiency: immediate and short term results of our first 60 procedures. AB - PURPOSE: To present the immediate and short-term results of our first 60 endovenous laser (EVL) ablation procedures. MATERIALS AND METHODS: Between July 2005 and December 2006, 60 EVL ablations were performed in 36 symptomatic patients (26 females, 10 males; mean age +/- SD, 46 +/- 14 years). The incompetent veins included the great saphenous vein (GSV) (n = 52), small saphenous vein (n = 6), and major branches of the GSV (n = 2). In all cases incompetent veins were punctured under ultrasound (US) guidance and the laser fiber was placed into these veins through a vascular sheath or with the help of a catheter. After tumescent anesthesia was administered, the veins were ablated with laser by delivering 50-100 joules/cm energy to the vein wall. Following EVL ablations, 29 patients also underwent foam sclerotherapy to treat the remaining varicosities. After the EVL ablation +/- sclerotherapy, patients were followed- up with Doppler US at 1 week, and then 3, 6, and 12 months post procedure. RESULTS: In all patients EVL ablation was technically successful. Complications were minor and included transient visual disturbance due to foam sclerotherapy (n = 1), bruising/ ecchymoses (n = 24), postoperative pain (n = 16), and superficial thrombophlebitis (n = 6). All patients returned to normal activity within 2 days. During the 7 +/- 5 months (mean +/- SD) of follow-up, recurrent reflux was seen in only one patient, in both GSVs, which was successfully treated with foam sclerotherapy. CONCLUSION: EVL ablation is a safe and effective method for the management of saphenous vein insufficiency. PMID- 17846993 TI - Embolization of benign and malignant bone and soft tissue tumors of the extremities. AB - PURPOSE: To reveal the effectiveness and reliability of preoperative, curative, and palliative embolization of benign and malignant bone and soft tissue tumors of the extremities. MATERIALS AND METHODS: Diagnostic angiography was performed on 35 patients (14 females, 40%; 21 males, 60%) between 6 and 70 years of age (mean, 32 years) who were referred to our digital subtraction angiography (DSA) unit between March 2000 and March 2004, and had extremity bone or soft tissue tumors. Among 17 patients who were initially assessed to be appropriate for angiographic embolization, DSA-assisted intra-arterial embolization was performed on 11 pre-operatively, and 6 curatively or palliatively. Effectiveness of the procedure was evaluated using imaging modalities, including angiography, X-ray, computed tomography, and magnetic resonance imaging as well as with post operative findings. RESULTS: Among the 11 patients that underwent pre-operative embolization, 10 showed a significant reduction in intra-operative and early post operative bleeding. Additionally, manipulation and excision of the tumors during surgery were easier as a result. Partial or full remission occurred in 3 of 6 patients that underwent lesion embolization. Two other patients had surgical procedures after finding their lesions had increased in size. In one patient with stable lesion size, cranial metastasis was discovered later. CONCLUSION: Pre operative, palliative, and curative selective/superselective intra-arterial embolization is an effective and potentially developing method for benign and malignant, hypervascularized bone and soft tissue tumors of the extremities, when it is performed by an experienced team with proper embolizing agents. PMID- 17846994 TI - A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. AB - A single missense mutation was identified in a novel, highly conserved zinc finger gene, ZCD2, in three consanguineous families of Jordanian descent with Wolfram syndrome (WFS). It had been shown that these families did not have mutations in the WFS1 gene (WFS1) but were mapped to the WFS2 locus at 4q22-25. A G-->C transversion at nucleotide 109 predicts an amino acid change from glutamic acid to glutamine (E37Q). Although the amino acid is conserved and the mutation is nonsynonymous, the pathogenesis for the disorder is because the mutation also causes aberrant splicing. The mutation was found to disrupt messenger RNA splicing by eliminating exon 2, and it results in the introduction of a premature stop codon. Mutations in WFS1 have also been found to cause low-frequency nonsyndromic hearing loss, progressive hearing loss, and isolated optic atrophy associated with hearing loss. Screening of 377 probands with hearing loss did not identify mutations in the WFS2 gene. The WFS1-encoded protein, Wolframin, is known to localize to the endoplasmic reticulum and plays a role in calcium homeostasis. The ZCD2-encoded protein, ERIS (endoplasmic reticulum intermembrane small protein), is also shown to localize to the endoplasmic reticulum but does not interact directly with Wolframin. Lymphoblastoid cells from affected individuals show a significantly greater rise in intracellular calcium when stimulated with thapsigargin, compared with controls, although no difference was observed in resting concentrations of intracellular calcium. PMID- 17846995 TI - Simultaneous discovery and testing of deletions for disease association in SNP genotyping studies. AB - Copy-number variation (CNV), and deletions in particular, can play a crucial, causative role in rare disorders. The extent to which CNV contributes to common, complex disease etiology, however, is largely unknown. Current techniques to detect CNV are relatively expensive and time consuming, making it difficult to conduct the necessary large-scale genetic studies. SNP genotyping technologies, on the other hand, are relatively cheap, thereby facilitating large study designs. We have developed a computational tool capable of harnessing the information in SNP genotype data to detect deletions. Our approach not only detects deletions with high power but also returns accurate estimates of both the population frequency and the transmission frequency. This tool, therefore, lends itself to the discovery of deletions in large familial SNP genotype data sets and to simultaneous testing of the discovered deletion for association, with the use of both frequency-based and transmission/disequilibrium test-based designs. We demonstrate the effectiveness of our computer program (microdel), available for download at no cost, with both simulated and real data. Here, we report 693 deletions in the HapMap 16c collection, with each deletion assigned a population frequency. PMID- 17846996 TI - TBX22 missense mutations found in patients with X-linked cleft palate affect DNA binding, sumoylation, and transcriptional repression. AB - The T-box transcription factor TBX22 is essential for normal craniofacial development, as demonstrated by the finding of nonsense, frameshift, splice-site, or missense mutations in patients with X-linked cleft palate (CPX) and ankyloglossia. To better understand the function of TBX22, we studied 10 different naturally occurring missense mutations that are phenotypically equivalent to loss-of-function alleles. Since all missense mutations are located in the DNA-binding T-box domain, we first investigated the preferred recognition sequence for TBX22. Typical of T-box proteins, the resulting sequence is a palindrome based around near-perfect copies of AGGTGTGA. DNA-binding assays indicate that missense mutations at or near predicted contact points with the DNA backbone compromise stable DNA-protein interactions. We show that TBX22 functions as a transcriptional repressor and that TBX22 missense mutations result in impaired repression activity. No effect on nuclear localization of TBX22 was observed. We find that TBX22 is a target for the small ubiquitin-like modifier SUMO-1 and that this modification is required for TBX22 repressor activity. Although the site of SUMO attachment at the lysine at position 63 is upstream of the T-box domain, loss of SUMO-1 modification is consistently found in all pathogenic CPX missense mutations. This implies a general mechanism linking the loss of SUMO conjugation to the loss of TBX22 function. Orofacial clefts are well known for their complex etiology and variable penetrance, involving both genetic and environmental risk factors. The sumoylation process is also subject to and profoundly affected by similar environmental stresses. Thus, we suggest that SUMO modification may represent a common pathway that regulates normal craniofacial development and is involved in the pathogenesis of both Mendelian and idiopathic forms of orofacial clefting. PMID- 17846998 TI - Simultaneously correcting for population stratification and for genotyping error in case-control association studies. AB - In population-based case-control association studies, the regular chi (2) test is often used to investigate association between a candidate locus and disease. However, it is well known that this test may be biased in the presence of population stratification and/or genotyping error. Unlike some other biases, this bias will not go away with increasing sample size. On the contrary, the false positive rate will be much larger when the sample size is increased. The usual family-based designs are robust against population stratification, but they are sensitive to genotype error. In this article, we propose a novel method of simultaneously correcting for the bias arising from population stratification and/or for the genotyping error in case-control studies. The appropriate corrections depend on sample odds ratios of the standard 2x3 tables of genotype by case and control from null loci. Therefore, the test is simple to apply. The corrected test is robust against misspecification of the genetic model. If the null hypothesis of no association is rejected, the corrections can be further used to estimate the effect of the genetic factor. We considered a simulation study to investigate the performance of the new method, using parameter values similar to those found in real-data examples. The results show that the corrected test approximately maintains the expected type I error rate under various simulation conditions. It also improves the power of the association test in the presence of population stratification and/or genotyping error. The discrepancy in power between the tests with correction and those without correction tends to be more extreme as the magnitude of the bias becomes larger. Therefore, the bias correction method proposed in this article should be useful for the genetic analysis of complex traits. PMID- 17846997 TI - Clinical and molecular phenotype of Aicardi-Goutieres syndrome. AB - Aicardi-Goutieres syndrome (AGS) is a genetic encephalopathy whose clinical features mimic those of acquired in utero viral infection. AGS exhibits locus heterogeneity, with mutations identified in genes encoding the 3'-->5' exonuclease TREX1 and the three subunits of the RNASEH2 endonuclease complex. To define the molecular spectrum of AGS, we performed mutation screening in patients, from 127 pedigrees, with a clinical diagnosis of the disease. Biallelic mutations in TREX1, RNASEH2A, RNASEH2B, and RNASEH2C were observed in 31, 3, 47, and 18 families, respectively. In five families, we identified an RNASEH2A or RNASEH2B mutation on one allele only. In one child, the disease occurred because of a de novo heterozygous TREX1 mutation. In 22 families, no mutations were found. Null mutations were common in TREX1, although a specific missense mutation was observed frequently in patients from northern Europe. Almost all mutations in RNASEH2A, RNASEH2B, and RNASEH2C were missense. We identified an RNASEH2C founder mutation in 13 Pakistani families. We also collected clinical data from 123 mutation-positive patients. Two clinical presentations could be delineated: an early-onset neonatal form, highly reminiscent of congenital infection seen particularly with TREX1 mutations, and a later-onset presentation, sometimes occurring after several months of normal development and occasionally associated with remarkably preserved neurological function, most frequently due to RNASEH2B mutations. Mortality was correlated with genotype; 34.3% of patients with TREX1, RNASEH2A, and RNASEH2C mutations versus 8.0% RNASEH2B mutation-positive patients were known to have died (P=.001). Our analysis defines the phenotypic spectrum of AGS and suggests a coherent mutation-screening strategy in this heterogeneous disorder. Additionally, our data indicate that at least one further AGS-causing gene remains to be identified. PMID- 17846999 TI - A chromosome 11q quantitative-trait locus influences change of blood-pressure measurements over time in Mexican Americans of the San Antonio Family Heart Study. AB - Although previous genome scans have searched for quantitative-trait loci (QTLs) influencing variation in blood pressure (BP), few have investigated the rate of change in BP over time as a phenotype. Here, we compare results from genomewide scans to localize QTLs for systolic, diastolic, and mean arterial BPs (SBP, DBP, and MBP, respectively) and for rates of change in systolic, diastolic, and mean arterial BPs (rSBP, rDBP, and rMBP, respectively), with use of the longitudinal data collected about Mexican Americans of the San Antonio Family Heart Study (SAFHS). Significant evidence of linkage was found for rSBP (LOD 4.15) and for rMBP (LOD 3.94) near marker D11S4464 located on chromosome 11q24.1. This same chromosome 11q region also shows suggestive linkage to SBP (LOD 2.23) and MBP (LOD 2.37) measurements collected during the second clinic visit. Suggestive evidence of linkage to chromosome 5 was also found for rMBP, to chromosome 16 for rSBP, and to chromosomes 1, 5, 6, 7, and 21 for the single-time-point BP traits collected at the first two SAFHS clinic visits. We also present results from fine mapping the chromosome 11 QTL with use of SNP-association analysis within candidate genes identified from a bioinformatic search of the region and from whole-genome transcriptional expression data collected from 1,240 SAFHS participants. Our results show that the use of longitudinal BP data to calculate the rate of change in BP over time provides more information than do the single time measurements, since they reveal physiological trends in the subjects that a single-time measurement could never capture. Further investigation of this region is necessary for the identification of the genetic variation responsible for QTLs influencing the rate of change in BP. PMID- 17847000 TI - Cowden syndrome-affected patients with PTEN promoter mutations demonstrate abnormal protein translation. AB - Germline mutations of PTEN (phosphatase and tensin homolog deleted on chromosome 10) are associated with the multihamartomatous disorder Cowden syndrome (CS). Moreover, patients with CS with germline PTEN promoter mutations have aberrant PTEN protein expression and an increased frequency of breast cancer. Here, we examined the downstream effect of five PTEN promoter variants (-861G/T, -853C/G, 834C/T, -798G/C, and -764G/A) that are not within any known cis-acting regulatory elements. Clinically, all five of these patients have been given diagnoses of breast, thyroid, and/or endometrial cancer. We demonstrated that protein binding to the PTEN promoter (-893 to -755) was not altered in the five variants when compared with the wild-type (WT) promoter. However, reporter assays indicated that three of the variants (-861G/T, -853C/G, and -764G/A) demonstrated an ~50% decrease in luciferase activity compared with the WT construct. PTEN messenger RNA (mRNA) levels were not altered in these variants, whereas secondary structure predictions indicated that different PTEN 5' untranslated region transcript folding patterns exist in three variants, suggesting an inhibition of protein translation. This was confirmed by PTEN protein analysis. These data indicate that variants causing large mRNA secondary structure alterations result in an inhibition of protein translation and a decrease in PTEN protein expression. These data emphasize the importance of PTEN promoter nucleotide variations and their ability to lead to CS progression by a novel regulatory mechanism. Importantly, these patients have a high prevalence of breast, thyroid, and endometrial malignancies; thus, understanding of the mechanism of PTEN dysfunction in these patients will lead to more-sensitive molecular diagnostic and predictive testing and, ultimately, to rational targeted therapies to treat or prevent malignancy. PMID- 17847001 TI - Copy-number variations measured by single-nucleotide-polymorphism oligonucleotide arrays in patients with mental retardation. AB - Whole-genome analysis using high-density single-nucleotide-polymorphism oligonucleotide arrays allows identification of microdeletions, microduplications, and uniparental disomies. We studied 67 children with unexplained mental retardation with normal karyotypes, as assessed by G-banded chromosome analyses. Their DNAs were analyzed with Affymetrix 100K arrays. We detected 11 copy-number variations that most likely are causative of mental retardation, because they either arose de novo (9 cases) and/or overlapped with known microdeletions (2 cases). The eight deletions and three duplications varied in size from 200 kb to 7.5 Mb. Of the 11 copy-number variations, 5 were flanked by low-copy repeats. Two of those, on chromosomes 15q25.2 and Xp22.31, have not been described before and have a high probability of being causative of new deletion and duplication syndromes, respectively. In one patient, we found a deletion affecting only a single gene, MBD5, which codes for the methyl-CpG binding domain protein 5. In addition to the 67 children, we investigated 4 mentally retarded children with apparent balanced translocations and detected four deletions at breakpoint regions ranging in size from 1.1 to 14 Mb. PMID- 17847002 TI - An LRP8 variant is associated with familial and premature coronary artery disease and myocardial infarction. AB - Our previous genomewide linkage scan of 428 nuclear families (GeneQuest) identified a significant genetic susceptibility locus for premature myocardial infarction (MI) on chromosome 1p34-36. We analyzed candidate genes in the locus with a population-based association study involving probands with premature coronary artery disease (CAD) and/or MI from the GeneQuest families (381 cases) and 560 controls without stenosis detectable by coronary angiography. A nonconservative substitution, R952Q, in LRP8 was significantly associated with susceptibility to premature CAD and/or MI by use of both population-based and family-based designs. Three additional white populations were used for follow-up replication studies: another independent cohort of CAD- and/or MI-affected families (GeneQuest II: 441 individuals from 22 pedigrees), an Italian cohort with familial MI (248 cases) and 308 Italian controls, and a separate Cleveland GeneBank cohort with sporadic MI (1,231 cases) and 560 controls. The association was significantly replicated in two independent populations with a family history of CAD and/or MI, the GeneQuest II family-based replication cohort and the Italian cohort, but not in the population with sporadic disease. The R952Q variant of LRP8 increased activation of p38 mitogen-activated protein kinase by oxidized low-density lipoprotein. This extensive study, involving multiple independent populations, provides the first evidence that genetic variants in LRP8 may contribute to the development of premature and familial CAD and MI. PMID- 17847003 TI - A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation. AB - Nonsyndromic mental retardation is one of the most important unresolved problems in genetic health care. Autosomal forms are far more common than X-linked forms, but, in contrast to the latter, they are still largely unexplored. Here, we report a complex mutation in the ionotropic glutamate receptor 6 gene (GRIK2, also called "GLUR6") that cosegregates with moderate-to-severe nonsyndromic autosomal recessive mental retardation in a large, consanguineous Iranian family. The predicted gene product lacks the first ligand-binding domain, the adjacent transmembrane domain, and the putative pore loop, suggesting a complete loss of function of the GLU(K6) protein, which is supported by electrophysiological data. This finding provides the first proof that GLU(K6) is indispensable for higher brain functions in humans, and future studies of this and other ionotropic kainate receptors will shed more light on the pathophysiology of mental retardation. PMID- 17847004 TI - Common variants in the BMP2, BMP4, and HJV genes of the hepcidin regulation pathway modulate HFE hemochromatosis penetrance. AB - Most cases of genetic hemochromatosis (GH) are associated with the HFE C282Y/C282Y (p.Cys282Tyr/p.Cys282Tyr) genotype in white populations. The symptoms expressed by C282Y homozygotes are extremely variable. Only a few suffer from an overt disease. Several studies have suggested that, in addition to environmental factors, a genetic component could explain a substantial part of this phenotypic variation, although very few genetic factors have been identified so far. In the present study, we tested the association between common variants in candidate genes and hemochromatosis penetrance, in a large sample of C282Y homozygotes, using pretherapeutic serum ferritin level as marker of hemochromatosis penetrance. We focused on two biologically relevant gene categories: genes involved in non-HFE GH (TFR2, HAMP, and SLC40A1) and genes involved in the regulation of hepcidin expression, including genes from the bone morphogenetic protein (BMP) regulatory pathway (BMP2, BMP4, HJV, SMAD1, SMAD4, and SMAD5) and the IL6 gene from the inflammation-mediated regulation pathway. A significant association was detected between serum ferritin level and rs235756, a common single-nucleotide polymorphism (SNP) in the BMP2 genic region (P=4.42x10-5). Mean ferritin level, adjusted for age and sex, is 655 ng/ml among TT genotypes, 516 ng/ml in TC genotypes, and 349 ng/ml in CC genotypes. Our results further suggest an interactive effect on serum ferritin level of rs235756 in BMP2 and a SNP in HJV, with a small additive effect of a SNP in BMP4. This first reported association between common variants in the BMP pathway and iron burden suggests that full expression of HFE hemochromatosis is linked to abnormal liver expression of hepcidin, not only through impairment in the HFE function but also through functional modulation in the BMP pathway. Our results also highlight the BMP regulation pathway as a good candidate for identification of new modifier genes. PMID- 17847005 TI - A Bayesian approach to copy-number-polymorphism analysis in nuclear pedigrees. AB - Segmental copy-number polymorphisms (CNPs) represent a significant component of human genetic variation and are likely to contribute to disease susceptibility. These potentially multiallelic and highly polymorphic systems present new challenges to family-based genetic-analysis tools that commonly assume codominant markers and allow for no genotyping error. The copy-number quantitation (CNP phenotype) represents the total number of segmental copies present in an individual and provides a means to infer, rather than to observe, the underlying allele segregation. We present an integrated approach to meet these challenges, in the form of a graphical model in which we infer the underlying CNP phenotype from the (single or replicate) quantitative measure within the analysis while assuming an allele-based system segregating through the pedigree. This approach can be readily applied to the study of any form of genetic measure, and the construction permits extension to a wide variety of hypothesis tests. We have implemented the basic model for use with nuclear families, and we illustrate its application through an analysis of the CNP located in gene CCL3L1 in 201 families with asthma. PMID- 17847006 TI - Homozygous mutation in SPATA16 is associated with male infertility in human globozoospermia. AB - Globozoospermia is a rare (incidence <0.1% in male infertile patients) form of teratozoospermia, mainly characterized by round-headed spermatozoa that lack an acrosome. It originates from a disturbed spermiogenesis, which is expected to be induced by a genetic factor. Several family cases and recessive mouse models with the same phenotype support this expectation. In this study, we present a consanguineous family with three affected brothers, in whom we have identified a homozygous mutation in the spermatogenesis-specific gene SPATA16. This is the first example of a nonsyndromic male infertility condition in humans caused by an autosomal gene defect, and it could also mean that the identification of other partners like SPATA16 could elucidate acrosome formation. PMID- 17847007 TI - Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. AB - Odonto-onycho-dermal dysplasia is a rare autosomal recessive syndrome in which the presenting phenotype is dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of the skin. We studied three consanguineous Lebanese Muslim Shiite families that included six individuals affected with odonto-onycho-dermal dysplasia. Using a homozygosity mapping strategy, we assigned the disease locus to an ~9-cM region at chromosome 2q35-q36.2, located between markers rs16853834 and D2S353, with a maximum multipoint LOD score of 5.7. Screening of candidate genes in this region led us to identify the same c.697G-->T (p.Glu233X) homozygous nonsense mutation in exon 3 of the WNT10A gene in all patients. At the protein level, the mutation is predicted to result in a premature truncated protein of 232 aa instead of 417 aa. This is the first report to our knowledge of a human phenotype resulting from a mutation in WNT10A, and it is the first demonstration of an ectodermal dysplasia caused by an altered WNT signaling pathway, expanding the list of WNT-related diseases. PMID- 17847008 TI - Allele-specific targeting of microRNAs to HLA-G and risk of asthma. AB - HLA-G is a nonclassic, class I HLA molecule that has important immunomodulatory properties. Previously, we identified HLA-G as an asthma-susceptibility gene and discovered that the risk of asthma in a child was determined by both the child's HLA-G genotype and the mother's affection status. Here we report a SNP in the 3' untranslated region of HLA-G that influences the targeting of three microRNAs (miRNAs) to this gene, and we suggest that allele-specific targeting of these miRNAs accounts, at least in part, for our earlier observations on HLA-G and the risk of asthma. PMID- 17847009 TI - Mutations in CD96, a member of the immunoglobulin superfamily, cause a form of the C (Opitz trigonocephaly) syndrome. AB - The C syndrome is characterized by trigonocephaly and associated anomalies, such as unusual facies, psychomotor retardation, redundant skin, joint and limb abnormalities, and visceral anomalies. In an individual with the C syndrome who harbors a balanced chromosomal translocation, t(3;18)(q13.13;q12.1), we discovered that the TACTILE gene for CD96, a member of the immunoglobulin superfamily, was disrupted at the 3q13.3 breakpoint. In mutation analysis of nine karyotypically normal patients given diagnoses of the C or C-like syndrome, we identified a missense mutation (839C-->T, T280M) in exon 6 of the CD96 gene in one patient with the C-like syndrome. The missense mutation was not found among 420 unaffected Japanese individuals. Cells with mutated CD96 protein (T280M) lost adhesion and growth activities in vitro. These findings indicate that CD96 mutations may cause a form of the C syndrome by interfering with cell adhesion and growth. PMID- 17847010 TI - Geographically separate increases in the frequency of the derived ADH1B*47His allele in eastern and western Asia. AB - The ADH1B Arg47His polymorphism has been convincingly associated with alcoholism in numerous studies of several populations in Asia and Europe. In a review of literature from the past 30 years, we have identified studies that report allele frequencies of this polymorphism for 131 population samples from many different parts of the world. The derived ADH1B*47His allele reaches high frequencies only in western and eastern Asia. To pursue this pattern, we report here new frequency data for 37 populations. Most of our data are from South and Southeast Asia and confirm that there is a low frequency of this allele in the region between eastern and western Asia. The distribution suggests that the derived allele increased in frequency independently in western and eastern Asia after humans had spread across Eurasia. PMID- 17847011 TI - The variant inv(2)(p11.2q13) is a genuinely recurrent rearrangement but displays some breakpoint heterogeneity. AB - Human chromosome 2 contains large blocks of segmental duplications (SDs), both within and between proximal 2p and proximal 2q, and these may contribute to the frequency of the common variant inversion inv(2)(p11.2q13). Despite their being cytogenetically homogeneous, we have identified four different breakpoint combinations by fluorescence in situ hybridization mapping of 40 cases of inv(2)(p11.2q13) of European origin. For the vast majority of inversions (35/40), the breakpoints fell within the same spanning BACs, which hybridized to both 2p11.2 and 2q13 on the normal and inverted homologues. Sequence analysis revealed that these BACs contain a significant proportion of intrachromosomal SDs with sequence homology to the reciprocal breakpoint region. In contrast, BACs spanning the rare breakpoint combinations contain fewer SDs and with sequence homology only to the same chromosome arm. Using haplotype analysis, we identified a number of related family subgroups with identical or very closely related haplotypes. However, the majority of cases were not related, demonstrating for the first time that the inv(2)(p11.2q13) is a truly recurrent rearrangement. Therefore, there are three explanations to account for the frequent observation of the inv(2)(p11.2q13): the majority have arisen independently in different ancestors, while a minority either have been transmitted from a common founder or have different breakpoints at the molecular cytogenetic level. PMID- 17847012 TI - Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia. AB - Homozygosity mapping was performed in a consanguineous Sephardic Jewish family with three patients who presented with severe infantile encephalopathy associated with pontocerebellar hypoplasia and multiple mitochondrial respiratory-chain defects. This resulted in the identification of an intronic mutation in RARS2, the gene encoding mitochondrial arginine-transfer RNA (tRNA) synthetase. The mutation was associated with the production of an abnormally short RARS2 transcript and a marked reduction of the mitochondrial tRNA(Arg) transcript in the patients' fibroblasts. We speculate that missplicing mutations in mitochondrial aminoacyl-tRNA synthethase genes preferentially affect the brain because of a tissue-specific vulnerability of the splicing machinery. PMID- 17847013 TI - Re: the use of inferred haplotypes in downstream analysis. PMID- 17847015 TI - Impact of array comparative genomic hybridization-derived information on genetic counseling demonstrated by prenatal diagnosis of the TAR (thrombocytopenia-absent radius) syndrome-associated microdeletion 1q21.1. PMID- 17847017 TI - Psychiatric disorders in advanced cancer. AB - BACKGROUND: Emotional distress and psychiatric disorders are common among patients with advanced cancer. Oncologists play an important role in screening for these conditions, providing first-line treatment and referring patients for further evaluation and treatment when indicated. METHODS: The literature on psycho-oncology was reviewed, focusing on the epidemiology, assessment, and treatment of psychiatric disorders (adjustment disorders, major depression, anxiety and post-traumatic stress, personality disorders, substance abuse, and major mental disorders such as schizophrenia and bipolar disorder) in patients with advanced cancer. Communication skills and the role of the oncologist in dealing with end-of-life issues were also reviewed. Relevant data were summarized from the most recent systematic reviews, epidemiological studies, and intervention trials. Clinical recommendations are provided. RESULTS: About 50% of patients with advanced cancer meet criteria for a psychiatric disorder, the most common being adjustment disorders (11%-35%) and major depression (5%-26%). Both psychosocial and pharmacological treatments are effective for anxiety and depression, although existing studies have methodological limitations. Collaboration with mental health specialists is recommended for patients with personality disorders, major mental illness, and substance abuse problems. Effective communication involves active listening, exploring emotion and meaning, addressing prognosis, and discussing end-of-life issues when relevant. CONCLUSIONS: Treating psychiatric conditions improves quality of life in patients with advanced cancer. Oncologists play a key role in screening for psychiatric disorders, initiating first-line treatments for depression and anxiety, and communicating with patients and caregivers about prognosis and end-of-life issues. PMID- 17847016 TI - Fatigue after treatment for early stage breast cancer: a controlled comparison. AB - BACKGROUND: Evidence suggests that fatigue may be a greater problem for cancer survivors than people without cancer. The present study sought to determine whether fatigue was greater in women who had completed treatment for early-stage breast cancer relative to a demographically matched comparison group of women with no cancer history. METHODS: As part of a larger study, women with stage 0-II breast cancer were recruited before the start of chemotherapy and radiotherapy (n = 100) or radiotherapy only (n = 121). Fatigue was assessed at the end of treatment and 2, 4, and 6 months later. An age- and geographically matched sample of women with no history of cancer was recruited and assessed for comparison purposes. RESULTS: Relative to comparison subjects, breast cancer survivors reported more days of fatigue in the past week at all 4 study assessments (P < .05). These differences appeared to be clinically meaningful in that a greater percentage of patients than nonpatients earned scores in the abnormal range on this measure at each assessment (P < .05). Additional analyses indicated that differences in fatigue between patients and comparison subjects were attributable primarily to heightened fatigue in women who received both chemotherapy and radiotherapy. CONCLUSIONS: Findings suggest that fatigue is a greater problem for breast cancer survivors in the 6 months after completion of chemotherapy than for women with no cancer history. Future research should include longer-term follow up to determine the persistence of fatigue in this population of survivors. PMID- 17847018 TI - Structural analysis of substance P using molecular dynamics and NMR spectroscopy. AB - The present work is a combined structural study, using Nuclear Magnetic Resonance (NMR) and Molecular Dynamics(MD), of the amidated and the free acid forms of substance P in water and methanol. The results obtained using both approaches were compared in order to characterize the structural features of both peptides in solution. From the NMR experiments it was derived that the free acid form adopts an extended conformation at the N-terminus and a helical conformation at the C-terminal segment of the peptide in both water and methanol; these structural features are in qualitative agreement with the results of the MD simulations. No significant differences in behavior were observed between the amidated and the free acid forms of the peptide in the simulations and in the experiments carried out in water, suggesting that the different activities of these analogs are due to their different mode of interaction with the receptor rather than to their structural preferences. Finally, we propose that the structure of substance P can be partially inferred from its sequence due to the presence of a Pro-X-Pro motif on the N-terminus and a Gly-Leu sequence on the C terminus. PMID- 17847019 TI - QSAR modeling and computer-aided design of antimicrobial peptides. AB - The drastic increase in multi-drug-resistant bacteria has created an urgent need for new therapeutic interventions, including antimicrobial peptides, an interesting template for novel drug development. However, the process of optimizing peptide antimicrobial activity and specificity using large peptide libraries is both tedious and expensive. Here we confirm the use of a mathematical model for prediction, prior to synthesis, of peptide antibacterial activity toward the antibiotic resistant pathogen Pseudomonas aeruginosa. By the use of novel descriptors quantifying the contact energy between neighboring amino acids, as well as a set of inductive and conventional QSAR descriptors, we were able to model the antibacterial activity of peptides. Cross-correlation and optimization of the implemented descriptor values enabled us to build two models, using very limited sets of peptides, which were able to correctly predict the activity of 85 or 71% of the tested peptides, within a twofold deviation window of the corresponding previously assessed IC(50) values, measured earlier. Though these two models were significantly different in size, they demonstrated no significant difference in their predictive power, implying that it is possible to build powerful predictive models using even small sets of structurally different peptides, when using contact-energy descriptors and inductive and conventional QSAR descriptors in the model design. PMID- 17847020 TI - Oral contraceptive use, hormone replacement therapy, reproductive history and risk of colorectal cancer in women. AB - Evidence from epidemiologic studies suggests a possible role of exogenous and endogenous hormones in colorectal carcinogenesis in women. However, with respect to exogenous hormones, in contrast to hormone replacement therapy, few cohort studies have examined oral contraceptive use in relation to colorectal cancer risk. We used data from a large cohort study of Canadian women enrolled in a randomized controlled trial of breast cancer screening to assess the association of oral contraceptive use, hormone replacement therapy and reproductive factors with risk of colorectal cancer, overall and by subsite within the colorectum. Cancer incidence and mortality were ascertained by linkage to national databases. Among 89,835 women aged 40-59 at enrollment and followed for an average of 16.4 years, we identified 1,142 incident colorectal cancer cases. Proportional hazards models were used to estimate the associations between the exposures of interest and risk of colorectal cancer. Ever use of oral contraceptives at baseline was associated with a modest reduction in the risk of colorectal cancer (hazard ratio 0.83, 95% confidence interval 0.73-0.94), with similar effects for different subsites within the colorectum. No trend was seen in the hazard ratios with increasing duration of oral contraceptive use. No associations were seen with use of hormone replacement therapy (ever use or duration of use) or reproductive factors. Our results are suggestive of an inverse association between oral contraceptive use and colorectal carcinogenesis. However, given the lack of a dose-response relationship and the potential for confounding, studies with more complete assessment of exogenous hormone use throughout the life course are needed to clarify this association. PMID- 17847021 TI - Methylseleninic acid inhibits microvascular endothelial G1 cell cycle progression and decreases tumor microvessel density. AB - Our previous work has shown that the cancer chemopreventive effect of selenium may in part be mediated by its antiangiogenic activities and that methylseleninic acid (MSeA) can induce G1 arrest of human umbilical vein endothelial (macrovascular) cells. The objectives of the current study are to verify MSeA induced G1 arrest effect in microvascular endothelial cells and to elucidate the molecular mediators and targets involved. Flow cytometric analysis after MSeA exposure (2-10 microM) of telomerase-immortalized microvascular endothelial (TIME) cells for 24 hr showed aconcentration-dependent increase of G1-arrested cells. MSeA (3 microM) treatment delayed the mitogen-stimulated progression of TIME cells from G1 to S phase. These effects of MSeA were accompanied by an early transient (6 hr) upregulation of P21/CIP1 and P27/KIP1 and a delayed modest increase of P16/INK4a (12 hr). MSeA increased P27/KIP1 mRNA transcript level and slowed the turnover of P21/CIP1 protein. MSeA-treated cells contained elevated levels of bound P16/INK4a within the CDK4/6/cyclin D1 complexes as well as bound P21/CIP1 and P27/KIP1 within the CDK2/cyclin E complex and decreased their kinase activities. MSeA suppressed the mitogen/CDK-driven phosphorylative inactivation of retinoblastoma (Rb) protein, diminishing E2F1 release from Rb. In vivo, daily oral MSeA treatment of nude mice bearing subcutaneously inoculated human prostate cancer DU145 xenografts inhibited tumor growth in a dose-dependent manner. The microvessel density of the tumors in the high MSeA group was decreased by more than half from the control. An inhibition of mitogen-stimulated proliferation of endothelial cells by MSeA may therefore contribute to the inhibition of tumor angiogenesis. PMID- 17847022 TI - Organised mammography screening reduces breast cancer mortality: a cohort study from Finland. AB - We evaluated the effectiveness and the efficacy of population-based mammography programme in Finland, and explored associations between the screening performance and the screening efficacy. The main outcome, incidence-based mortality from breast cancer, was estimated by invitation, participation, age at death, and screening centres categorised by recall rates. The study was based on an individual followup of screening invitees and participants from 1992 to 2003. The coverage of screening invitations was 95% among 50-59 years old women, and 20-40% among women aged 60-69 years. We compared observed deaths from breast cancer to expected breast cancer deaths without screening in ages 50-69 at death. The observed deaths were obtained from a cohort of individual invitees (n = 361,848). The expected deaths were defined by modelling breast cancer mortality from 1974 to 1985 and 1992 to 2003 at population level. The population data were derived from the same municipalities (n = 260) that were incorporated into the cohort. The breast cancer mortality among the invited women was reduced by 22% (relative risk 0.78, 95% confidence interval 0.70-0.87). After adjusting for the self selection, the efficacy among the participants was 28% (0.72,0.56-0.88). No clear association between the recall rates and the screening efficacy was observed. The organised mammography screening in Finland is effective. The relationship between the estimates of process and outcome of mammography is not yet straightforward: effectiveness and efficacy remain the best estimates for evaluating the success of mammography screening. PMID- 17847023 TI - K-ras mutations and mucin profile in preneoplastic lesions and colon tumors induced in rats by 1,2-dimethylhydrazine. AB - K-ras and mucin profile variations, associated with intestinal carcinogenesis, were studied in the preneoplastic lesions, mucin-depleted foci (MDF) and aberrant crypt foci (ACF), and in colonic tumors induced in rats by 1,2-dimethylhydrazine (DMH). The frequency of lesions with K-ras mutations was 23% (3/13), 5.5% (1/18) and 100% (14/14) in MDF, tumors and ACF, respectively. Two of three MDF mutated in K-ras also carried a missense mutation in Apc. We also tested the expression of MUC2, a mucin abundantly expressed in normal colon and M1/MUCA5C, up-regulated in colon carcinogenesis, using immunohistochemistry. MDF and tumors showed a dramatic reduction in the expression of MUC2, whereas ACF showed only a slight reduction. The expression of M1/MUC5AC was almost absent in normal mucosa, but was increased in all the lesions (MDF, tumors and ACF). The expression of the intestinal trefoil factor (ITF), a marker of goblet cell lineage, was reduced in MDF and tumors compared to normal mucosa but not in ACF. In conclusion, although K-ras mutations are present in all ACF, they are less frequent in MDF and tumors; M1/MUC5AC is a marker associated with all preneoplastic events while the reduction of MUC2 and ITF expression is selectively associated with more advanced lesions such as MDF and tumors. PMID- 17847024 TI - Right coronary artery fistula-evaluation by multidector computed tomographic angiography. PMID- 17847025 TI - Giant unruptured sinus of valsalva aneurysm. PMID- 17847026 TI - Images in cardiology: right atrial diverticulum--a rare cause of atrial fibrillation. PMID- 17847027 TI - Subacute myocardial rupture evident on echocardiogram. PMID- 17847028 TI - Periaortic echolucency. PMID- 17847030 TI - Conditional approval: discussion points from the PSI conditional approval expert group. AB - The European Agency for the Evaluation of Medicinal Products has recently completed the consultation of a draft guidance on how to implement conditional approval. This route of application is available for orphan drugs, emergency situations and serious debilitating or life-threatening diseases. Although there has been limited experience in implementing conditional approval to date, PSI (Statisticians in the Pharmaceutical Industry) sponsored a meeting of pharmaceutical statisticians with an interest in the area to discuss potential issues. This article outlines the issues raised and resulting discussions, based on the group's interpretation of the legislation. Conditional approval seems to fit well with the accepted regulatory strategy in HIV. In oncology, conditional approval may be most likely when (a) compelling phase II data are available using accepted clinical outcomes (e.g. progression/recurrence-free survival or overall survival) and Phase III has been planned or started, or (b) when data are available using a surrogate endpoint for clinical outcome (e.g. response rate or biochemical measures) from a single-arm study in rare tumours with high response, compared with historical data. The use of interim analyses in Phase III for supporting conditional approval raises some challenging issues regarding dissemination of information, maintenance of blinding, potential introduction of bias, ethics, switching, etc. PMID- 17847031 TI - Tests for the homogeneity of two binomial proportions in extremely unbalanced 2 x 2 contingency tables. AB - Asymptotic tests such as the Pearson chi-square test are unreliable for testing the homogeneity of two binomial probabilities in extremely unbalanced cases. Two exact tests (conditional and unconditional) are available as alternatives and can be implemented easily in StatXact 6.0. In equal sample cases it is well known that the unconditional exact test is more powerful than the conditional exact test. However, in this paper, we show that the opposite result holds in extremely unbalanced cases. The reason is that the peaks of the type I error occur at the extremes of the nuisance parameter when the imbalance among the sample sizes becomes severe. After we show that the conditional exact test is more powerful than the unconditional exact test in extremely unbalanced cases whose sample ratio is greater than 20, we compare the conditional exact test with the Berger and Boos approach (J. Amer. Stat. Assoc. 1994; 89:1012-1016) in which the supremum is taken over a confidence interval for the nuisance parameter. The Berger and Boos approach turns out to be slightly more powerful than the conditional exact test in extremely unbalanced data. A real example is provided. PMID- 17847032 TI - Adenovirus-mediated expression of TIMP-1 and TIMP-2 in bone inhibits osteolytic degradation by human prostate cancer. AB - Matrix metalloproteinases (MMPs) are proteolytic enzymes that play critical roles in the pathogenesis of human cancers. Clinical trials using synthetic small molecule MMP inhibitors have been carried out but with little success. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors that block the extracellular matrix-degrading activity of MMPs. Here, we investigated the possibilities of genetically modifying human bones with TIMPs to create a high TIMP bone microenvironment, which is hostile to metastatic prostate cancer cells using adenovirus-mediated gene transfer technology and SCID-hu end-organ colonization mouse model. Two strategies were used to achieve bone-specific TIMP expression: (i) ex vivo bone adenoviral infection followed by in vivo bone implantation; and (ii) ex vivo BMS cell infection followed by injection into in vivo implanted human fetal bones. PC-3 prostate cancer cells were injected into human fetal bones 4 weeks after implantation in SCID mice. In vitro, adenovirus mediated expression of TIMP-1 or TIMP-2 in bone fragments inhibited MMP-2 activity, bone turnover and prostate cancer cell-induced proteolytic degradation as determined by gelatin zymography, calcium measurement and DQ protein quenched fluorescence assay, respectively. In vivo, immunohistochemistry confirmed TIMP-2 expression in AdTIMP-2-infected bone implants 4 weeks after implantation in SCID mice. Mice receiving AdTIMP-treated bone fragments showed significantly reduced PC-3-induced osteolysis, osteoclast recruitment and bone turnover in the implanted bones. We propose that adenoviral gene transfer of TIMP-1 and TIMP-2 can prevent the proteolytic activity of prostate cancer cells in bone and that enhancing anti-proteolytic defense mechanisms in target organs represents a promising form of prostate cancer gene therapy. PMID- 17847033 TI - Dulxanthone A induces cell cycle arrest and apoptosis via up-regulation of p53 through mitochondrial pathway in HepG2 cells. AB - Natural products derived from plants provide a rich source for development of new anticancer drugs. Dulxanthone A was found to be an active cytotoxic component in Garcinia cowa by bioactivity-directed isolation. Studies to elucidate the cytotoxic mechanisms of dulxanthone A showed that dulxanthone A consistently induced S phase arrest and apoptosis in the most sensitive cell line HepG2. Furthermore, p53 was dramatically up-regulated, leading to altered expression of downstream proteins upon dulxanthone A treatment. Cell cycle related proteins, such as cyclin A, cyclin B, cyclin E, cdc-2, p21 and p27 were down-regulated. Some apoptosis correlated proteins were also altered following the drug treatment. Bcl-2 family members PUMA was up-regulated while Bcl-2 and Bax were down-regulated. However, the expression ratio of Bax/Bcl-2 was increased. This resulted in the release of cytochrome C from the mitochondria to the cytosol. Concurrently, Apaf-1 was stimulated with p53 by dulxanthone A. In result, cytochrome C, Apaf-1 and procaspase-9 form an apoptosome, which in turn triggered the activation of caspase-9, caspase-3 and downstream caspase substrates. Lamin A/C and PARP were down-regulated or cleaved, respectively. Moreover, cell cycle arrest and apoptosis in HepG2 cells induced by dulxanthone A were markedly inhibited by siRNA knockdown of p53. In summary, dulxanthone A is an active cytotoxic component of G. cowa. It induces cell cycle arrest at lower concentrations and triggers apoptosis at higher concentrations via up-regulation of p53 through the intrinsic mitochondrial pathway in HepG2 cells. Dulxanthone A is therefore likely a promising preventive and/or therapeutic agent against Hepatoma. PMID- 17847034 TI - Systemic administration of a peptide that impairs the protein kinase (CK2) phosphorylation reduces solid tumor growth in mice. AB - The antitumor efficacy of the CK2 inhibitors so far described has not been extensively evaluated in cancer animal models. We have previously demonstrated that a proapoptotic cyclic peptide termed P15 delivered into the cells by the Tat Cell Penetrating Peptide was able to abrogate the CK2-mediated phosphorylation and induce tumor regression when injected directly into solid tumors in mice. Here we explored the antitumor effect by systemic administration of P15-Tat in a consecutive 5-day schedule through either intraperitoneal or intravenous route. Importantly, significant delay of tumor growth was observed at 2 mg/kg (p < 0.05), 10 mg/kg (p < 0.01) or 40 mg/kg (p < 0.001) after P15-Tat administration both in syngeneic murine tumors and human tumors xenografted in nude mice. In line with this, the systemic administration of P15-Tat induced apoptosis in the tumor as evidenced by in situ DNA fragmentation. Furthermore, we evidenced that 99mTc-labeled P15-Tat peptide was certainly accumulated on the tumors after administration by both routes. This report becomes the first describing the antitumor effect induced by systemic administration of a peptide that targets the acidic phosphorylation domain for CK2 substrates. Also, our data reinforces the perspectives of P15-Tat for the cancer targeted therapy. PMID- 17847035 TI - An unusual manifestation of Takotsubo cardiomyopathy. AB - Takotsubo cardiomyopathy typically presents with chest pain, ST changes, and transient left ventricular apical ballooning in the absence of epicardial coronary artery disease. This process is reversible and usually benign. An unusual manifestation is that of left ventricular outflow tract obstruction with systolic anterior motion of the mitral valve. Recognition of this finding is critical in patient management especially in the setting of cardiogenic shock, as inotropes are likely to aggravate and worsen the clinical condition. We provide a systematic review and an illustrative case and discuss treatment strategies. PMID- 17847036 TI - Brugada pattern unmasked by tricyclic antidepressant. PMID- 17847037 TI - Persistent left superior vena cava imaged by 64-detector computed tomography. PMID- 17847038 TI - The role of lipid-lowering therapy in preventing coronary heart disease in patients with type 2 diabetes. AB - Coronary heart disease is the most common cause of death among diabetic patients. The increased risk of coronary heart disease in type 2 diabetes is due, in part, to lipid abnormalities often present in the diabetic patient. Diabetic dyslipidemia is characterized by elevated triglycerides, low high-density lipoprotein cholesterol (HDL-C) and an increased preponderance of small, dense low-density lipoprotein cholesterol (LDL-C) particles. Current guidelines for the prevention of coronary heart disease in diabetic patients identify elevated LDL-C as the primary target of lipid-lowering therapy, and recommend statins as the first-line treatment for diabetic dyslipidemia. This review evaluates the large statin trials that have included diabetic patients, and discusses the role of combination therapy in managing dyslipidemia in diabetic patients. PMID- 17847039 TI - Amiodarone for atrial fibrillation following cardiac surgery: development of clinical practice guidelines at a university hospital. AB - Atrial fibrillation (AF) usually develops within the first 72 h following cardiac surgery, and is often self-limiting. Within 48 h of acute onset of symptoms, approximately 50% of patients spontaneously convert to normal sinus rhythm. Thus, the relative risks and benefits of therapy must be carefully considered. The etiology of AF following cardiac surgery is similar to that in non-surgical patients except that pericardial inflammation and increased adrenergic tone play an increasingly important role. Further, AF after surgery may be associated with transient risk factors that resolve as the patient moves out from surgery, and the condition is less likely to recur compared to AF arising in other circumstances. Immediate heart rate control is important in preventing ischemia, tachycardia-induced cardiomyopathy, and left ventricular dilatation. At our institution, amiodarone is frequently used as a first-line drug for treating AF after cardiac surgery. Inconsistent prescribing practices, variable dosage regimens, and a lack of consensus regarding the appropriate use of amiodarone prompted the need for developing practice guidelines. Multidisciplinary collaboration between the departments of cardiac surgery, pharmacy, and anesthesiology led to the development of a protocol for postoperative AF. We review the clinical evidence from published trials and discuss our guidelines, defining amiodarone use for AF in the cardiac surgery setting. PMID- 17847040 TI - Apical hypertrophic cardiomyopathy mimicking a septal infarct. PMID- 17847041 TI - Hyponatremia and vasopressin antagonism in congestive heart failure. AB - In a national heart failure registry, hyponatremia (serum sodium < 130 mEq/L) was initially reported in 5% of patients and considered a risk factor for increased morbidity and mortality. In a chronic heart failure study, serum sodium level on admission predicted an increased length of stay for cardiovascular causes and increased mortality within 60 days of discharge. Hyponatremia in patients with congestive heart failure (CHF) is associated with a higher mortality rate. Also, by monitoring and increasing serum sodium levels during hospitalization for CHF, patient outcomes may improve. This review describes the pathophysiology of hyponatremia in relation to CHF, including the mechanism of action of vasopressin receptors in the kidney, and assesses the preclinical and clinical trials of vasopressin receptor antagonists--agents recently developed to treat hyponatremia. In hospitalized patients with CHF, hyponatremia plays a major role in poor outcomes. Vasopressin receptor antagonists have been shown to be safe and effective in clinical trials in patients with hyponatremia. PMID- 17847042 TI - The late open infarct-related artery hypothesis: evidence-based medicine or not? AB - Randomized clinical trials have clearly shown that early reperfusion of coronary arteries is the established treatment of myocardial infarction preserving left ventricular function and reducing mortality. However, late patency of the infarct related artery is an independent predictor of survival leading to the late open artery hypothesis. This concept implies restoration of antegrade blood flow of the infarct-related artery in patients with myocardial infarction to improve survival by mechanisms less time-dependent or even time-independent. Possible explanations for this benefit include improved left ventricular function and electrical stability by perfusion of hibernating myocardium, accelerated infarct healing and limitation of ventricular remodeling. This review focuses on the evidence of late recanalization of occluded infarct-related arteries in patients with coronary artery disease. PMID- 17847043 TI - A rare cause of coronary spasm: epicardial infiltration of a B-cell lymphoma. PMID- 17847044 TI - Antiplatelet therapy in cerebrovascular disease: implications of Management of Artherothrombosis with Clopidogrel in High-risk Patients and the Clopidogrel for High Artherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance studies' results for cardiologists. AB - Cardiovascular disease is prevalent among patients with stroke; thus, cardiologists frequently treat patients at high risk for stroke. Results from recent clinical trials of antiplatelet medications, given alone or in combination, may be of special interest to cardiologists. The MATCH study demonstrated no significant difference between clopidogrel alone and clopidogrel plus aspirin in reducing risk of vascular events after stroke or transient ischemic attack. A 1.3% increased risk of major bleeding was associated with clopidogrel plus aspirin. In CHARISMA, clopidogrel plus aspirin did not reach statistical significance vs. placebo plus aspirin in reducing incidence of myocardial infarction (MI), stroke, or death from cardiovascular causes in patients with stable atherothrombotic disease; clopidogrel was associated with an increase in moderate bleeding. These results suggest that clopidogrel plus aspirin may be inappropriate as first-line therapy for secondary stroke prevention. In patients with established cardiovascular disease at risk for MI or other vascular events, physicians must weigh the benefits and risks before choosing this therapy. Selection of an antiplatelet agent must be based on patient history, including previous MI and stroke, susceptibility to bleeding, and other high-risk factors (e.g. advanced age and diabetes). Aspirin plus extended-release dipyridamole may be more effective than clopidogrel for preventing stroke in high-risk patients. This article strives to put MATCH and CHARISMA results into context by providing an overview of antiplatelet therapy, including relevant clinical trial results, a review of current practice guidelines, and a summary of an ongoing study that will improve clinical decision making. PMID- 17847045 TI - Dissection of left anterior descending artery following a motor vehicle accident. PMID- 17847046 TI - Coronary stent embolization into right common femoral artery - the role of computed tomography angiography. PMID- 17847047 TI - Fatal honeycomb mitral valve leaflet abscess. PMID- 17847048 TI - Complete lysis of left ventricular giant thrombus with anticoagulation therapy alone. PMID- 17847050 TI - Self-organization versus Watchmaker: ambiguity of molecular recognition and design charts of cellular circuitry. AB - A large body of experimental evidence indicates that the specific molecular interactions and/or chemical conversions depicted as links in the conventional diagrams of cellular signal transduction and metabolic pathways are inherently probabilistic, ambiguous and context-dependent. Being the inevitable consequence of the dynamic nature of protein structure in solution, the ambiguity of protein mediated interactions and conversions challenges the conceptual adequacy and practical usefulness of the mechanistic assumptions and inferences embodied in the design charts of cellular circuitry. It is argued that the reconceptualization of molecular recognition and cellular organization within the emerging interpretational framework of self-organization, which is expanded here to include such concepts as bounded stochasticity, evolutionary memory, and adaptive plasticity offers a significantly more adequate representation of experimental reality than conventional mechanistic conceptions do. Importantly, the expanded framework of self-organization appears to be universal and scale invariant, providing conceptual continuity across multiple scales of biological organization, from molecules to societies. This new conceptualization of biological phenomena suggests that such attributes of intelligence as adaptive plasticity, decision-making, and memory are enforced by evolution at different scales of biological organization and may represent inherent properties of living matter. PMID- 17847051 TI - The influence of rigid or flexible linkage between two ligands on the effective affinity and avidity for reversible interactions with bivalent receptors. AB - Bivalent or polyvalent cooperative binding between ligand and receptor is much tighter and more efficient than monovalent binding of the same counterparts. Because of this, many biological processes involve polyvalent binding for realization of regulatory mechanisms. For this reason it is necessary to develop a general formalism for prediction of the relationship between the binding affinities of each ligand subunits, the length of the flexible linker between them and avidity of the interaction. Here, we consider an approach that is based on the description of the state of equilibrium for the reaction of mono- and multivalent ligand-receptor binding of algebraic equation systems. This approach allows the evaluation of the avidity of bivalent binding and to determine the concentrations of ligand-receptor complexes, which will be obtained at the equilibrium state. The analysis presented here may be useful in analysing the binding behaviour of a bivalent receptor and a ligand consisting of two subunits covalently connected with a rigid or flexible linker. PMID- 17847052 TI - Use of instrumental variables in the analysis of generalized linear models in the presence of unmeasured confounding with applications to epidemiological research. AB - A major, often unstated, concern of researchers carrying out epidemiological studies of medical therapy is the potential impact on validity if estimates of treatment are biased due to unmeasured confounders. One technique for obtaining consistent estimates of treatment effects in the presence of unmeasured confounders is instrumental variables analysis (IVA). This technique has been well developed in the econometrics literature and is being increasingly used in epidemiological studies. However, the approach to IVA that is most commonly used in such studies is based on linear models, while many epidemiological applications make use of non-linear models, specifically generalized linear models (GLMs) such as logistic or Poisson regression. Here we present a simple method for applying IVA within the class of GLMs using the generalized method of moments approach. We explore some of the theoretical properties of the method and illustrate its use within both a simulation example and an epidemiological study where unmeasured confounding is suspected to be present. We estimate the effects of beta-blocker therapy on one-year all-cause mortality after an incident hospitalization for heart failure, in the absence of data describing disease severity, which is believed to be a confounder. PMID- 17847053 TI - Growing the mandible: role of the periosteum and its cells. AB - Mandibular periosteum moves in the direction of new apposition. This displacement, usually termed "migration," is thought to involve the fibrous layer of periosteum, with the deeper osteogenic layer remaining at its original location except for its blood vessels. To assess whether periosteal displacement includes cells as well as matrix and whether the osteogenic layer has a role, a longitudinal study was undertaken. Young pigs (n = 10) were injected with a replication marker and killed 3 hr, 2 weeks, or 4 weeks later. Sections of the mandibular ramus were scored for labeled cell density. Some sections were double labeled with lectin to identify blood vessels. Statistical differences were seen between but not within age groups. Three hours after labeling, the fibroblastic layer had sparse, evenly distributed replicating cells, whereas the osteogenic layer had numerous replicating cells, especially at the caudal border. At 2 and 4 weeks later, a decrease in labeled osteogenic layer cells was accompanied by an increase in labeled osteocytes. Zones of labeled osteocytes in these late sacrifice groups were used to approximate the position of the ramal borders at the time of injection. Beyond these zones, in active growing sites, labeled cells were found not only in the fibrous layer but also in the osteogenic layer and in bone. Therefore, periosteal displacement does involve cells and is not restricted to the fibrous layer. PMID- 17847054 TI - Cellular motors for molecular manufacturing. AB - Cells are composed of macromolecular structures of various sizes that act individually or collectively to maintain their viability and perform their function within the organism. This review focuses on one structure, the microtubule, and one of the motor proteins that move along it, conventional kinesin (kinesin 1). Recent work on the cellular functions of kinesins, such as the organization of microtubules during cellular division and the movement of the organelles and vesicles, offers insights into how biological motors might prove useful for organizing structures in engineered environments. PMID- 17847055 TI - Dynamics of the epithelium during canalization of the rat ventral prostate. AB - Outgrowth and branching of solid cords are the initial events in postnatal prostatic morphogenesis. These processes involve cell proliferation and their projection into the stroma and precede epithelial canalization. The purpose of the present study was to examine the dynamics of the prostate epithelium during canalization of the rat ventral prostate in the first week of postnatal development using histological, stereological, and ultrastructural analyses. The terminal deoxynucleotidyltransferase [TdT]-mediated deoxy-UTP nick end labeling assay was used to investigate the occurrence of DNA fragmentation. Our results demonstrate that canalization of the prostate epithelium starts as early as on day 1 (24 hr after birth) and progresses thereafter. By the end of the first week (day 6), luminal volume density reached approximately 3% (P < 0.05) of the organ. Canalization was the result of epithelial cell differentiation and apoptosis. The former involved organization of the epithelial cells into a single layer sitting on the basement membrane, polarization, enlargement of secretory organelles and accumulation of secretory vesicles, microvilli formation, and establishment of the adult pattern of cell junctions. The latter was observed to occur mostly to epithelial cells not in contact with the basement membrane. Structures of variable electron density were observed in the developing lumen. In conclusion, different phenomena seem to be involved in the canalization of the rat ventral prostate. However, it was evident from the present results that complex epithelial cell fate decisions take place during this process. PMID- 17847056 TI - High-resolution three-dimensional computer simulation of hominid cranial mechanics. AB - In vivo data demonstrates that strain is not distributed uniformly on the surface of the primate skull during feeding. However, in vivo studies are unable to identify or track changes in stress and strain throughout the whole structure. Finite element (FE) analysis, a powerful engineering tool long used to predict the performance of man-made devices, has the capacity to track stress/strain in three dimensions (3-D) and, despite the time-consuming nature of model generation, FE has become an increasingly popular analytical device among biomechanists. Here, we apply the finite element method using sophisticated computer models to examine whether 3-D stress and strain distributions are nonuniform throughout the primate skull, as has been strongly suggested by 2-D in vivo strain analyses. Our simulations document steep internal stress/strain gradients, using models comprising up to three million tetrahedral finite elements and 3-D reconstructions of jaw adducting musculature with both cranium and mandible in correct anatomical position. Results are in broad concurrence with the suggestion that few regions of the hominid cranium are clearly optimized for routine feeding and also show that external stress/strain does not necessarily reflect internal distributions. Findings further suggest that the complex heterogeneity of bone in the skull may act to dissipate stress, but that consequently higher strain must be offset by additional strain energy. We hypothesize that, despite energetic costs, this system may lend adaptive advantage through enhancing the organism's ability to modify its behavior before reaching catastrophic failure in bony or dental structures. PMID- 17847057 TI - Oligopotent mesenchymal stem cell-like clone becomes multinucleated following phorbol ester, TPA stimulation. AB - We established a mesenchymal stem cell clone, 5F9A, from rat bone marrow substrate adherent cells by repeated limiting dilutions. The cells have a fibroblastic shape and form intimate contacts with adjacent cells with interdigitations and junctions similar to adherence and tight junctions in a semi confluent culture. Analysis of the phenotypes of these cells by RT-PCR and FACS demonstrated that they resembled mesenchymal stem cells, and the cells could differentiate into adiopocytes and osteoblasts under appropriate conditions in vitro showing their oligopotency. Furthermore, the cells were induced to become multinuclear cells by TPA (12-o-tetradecanoylphorbol 13-acetate) stimulation. PMID- 17847058 TI - Age-specific prevalence and years of healthy life in a system with three health states. AB - Consider a 3-state system with one absorbing state, such as Healthy, Sick, and Dead. Over time, the prevalence of the Healthy state will approach an 'equilibrium' value that is independent of the initial conditions. We derived this equilibrium prevalence (Prev:Equil) as a function of the local transition probabilities. We then used Prev:Equil to estimate the expected number of years spent in the healthy state over time. This estimate is similar to the one calculated by multi-state life table methods, and has the advantage of having an associated standard error. In longitudinal data for older adults, the standard error was accurate when a valid survival table was known from other sources, or when the available data set was sufficient to estimate survival accurately. Performance was better with fewer waves of data. If validated in other situations, these estimates of prevalence and years of healthy life (YHL) and their standard errors may be useful when the goal is to compare YHL for different populations. PMID- 17847059 TI - ST elevation alternans in presence of profound myocardial ischemia and injury induced by cocaine toxicity. PMID- 17847060 TI - Apical aneurysm formation in hypertrophic cardiomyopathy with mid-ventricular obstruction. PMID- 17847061 TI - Encephalization, neuronal excess, and neuronal index in rodents. AB - Encephalization, or brain size larger than expected from body size, has long been considered to correlate with improved cognitive abilities across species and even intelligence. However, it is still unknown what characteristics of relatively large brains underlie their improved functions. Here, it is shown that more encephalized rodent species have the number of neurons expected for their brain size, but a larger number of neurons than expected for their body size. The number of neurons in excess relative to body size might be available for improved associative functions and, thus, be responsible for the cognitive advantage observed in more encephalized animals. It is further proposed that, if such neuronal excess does provide for improved cognitive abilities, then the total number of excess neurons in each species-here dubbed the neuronal index-should be a better indicator of cognitive abilities than the encephalization quotient (EQ). Because the neuronal index is a function of both the number of neurons expected from the size of the body and the absolute number of neurons in the brain, differences in this parameter across species that share similar EQs might explain why these often have different cognitive capabilities, particularly when comparing across mammalian orders. PMID- 17847062 TI - Predicted tracheobronchial and pulmonary deposition in a murine asthma model. AB - Particulate matter dosimetry provides the critical link between exposures and initial doses reaching various sites in the respiratory tract. To extrapolate findings from animal models to humans, quantitative respiratory-tract anatomical data dosimetry in these animal models is required. The goal of this study was to provide anatomical information for the tracheobronchial and pulmonary region so predictions of particle deposition could be performed for a widely used model of asthma; the sensitized Balb/c mouse. Tracheobronchial airway morphometry of sensitized male Balb/c mice was generated from three in situ prepared lung casts. Distribution of the number of generations to terminal bronchiole for each lung lobe was determined by assigning a unique binary number to each airway. This strategy enabled the median path length to terminal bronchiole to be determined. A total of 25 median length paths to terminal bronchiole were measured (airway length, diameter, and branch angle) in each lung cast. These 25 paths were proportionately distributed among the six lobes based upon the number of median length pathways in each cast. Airway length, diameter, and branch angle were measured for each airway in the 25 median length pathways. Measurements of airway length, diameter, and branch angle for each generation were averaged to create a typical path tracheobronchial anatomy model. A pulmonary airway model was also developed so that particle deposition predictions could be performed for particle diameters of 0.2-10 micrometers. Particle deposition efficiency predictions were consistent with in vivo measured deposition. PMID- 17847063 TI - Comparison of the pharmacokinetics of moxidectin and ivermectin after oral administration to beagle dogs. AB - This study compares plasma disposition kinetics of ivermectin and moxidectin after oral administration to beagle dogs experimentally infected with the filarial parasite, Brugia pahangi. Sixteen dogs were selected and randomly allocated into two groups of eight dogs each. Animals in each group received either ivermectin or moxidectin by oral route at a dose of 250 microg/kg. Blood samples were collected from 0.5 h up to 56 days post-treatment and the plasma was analysed by high performance liquid chromatography (HPLC). The obtained data were analysed by compartmental and non-compartmental pharmacokinetic techniques. Peak plasma concentrations (C(max)) of 234.0 +/- 64.3 ng/ml (mean +/- SD) were obtained for moxidectin and 132.6 +/- 43.0 ng/ml for ivermectin. The terminal elimination half-life was significantly (p<0.01) longer in the moxidectin treated group (621.3 +/- 149.3 h) than for ivermectin treated group (80.3 +/- 29.8 h). A significantly (p< 0.01) larger V(ss)/F was obtained for moxidectin (19.21 +/- 3.61 l/kg) compared with ivermectin (5.35 +/- 1.29 l/kg). The mean estimates of CL/F of moxidectin and ivermectin were 0.0220 +/- 0.00381 and 0.0498 +/- 0.0179 l/h/kg, respectively. The comparative plasma disposition kinetics of ivermectin and moxidectin in dogs is reported for the first time. PMID- 17847064 TI - Development and validation of a gas chromatography-mass spectrometry method for the determination of phenazopyridine in rat plasma: application to the pharmacokinetic study. AB - Phenazopyridine hydrochloride is a strong analgesic used in the treatment of urinary tract infections. The aim of the present study was to develop a procedure based on gas chromatography-mass spectrometry (GC-MS) for the analysis of phenazopyridine in rat plasma. The method was set up and adapted for the analysis of small biological samples taken from rats. Biological samples were extracted by liquid-liquid extraction. The extraction agent was ethyl acetate. The samples were separated by GC on a DB-5MS analytical column and determined by a quadrupole mass spectrometer detector operated under selected ion monitoring mode. Excellent linearity was found between 0.01 and 1.00 microg/ml (r = 0.9991, n = 9) for plasma samples. The limit of detection (LOD) was 0.3 ng/ml. Within-day and between-day precisions expressed as the relative standard deviation (RSD) for the method were 1.83-4.91% and 2.12-4.76%, respectively. The recoveries for all samples were >90%. The main pharmacokinetic parameters obtained were T(max) = (0.35+/-0.01) h, C(max) = (0.396+/-0.079) microg/ml, AUC = (0.373+/-0.065) h microg/ml and CL = (94.2+/-5.9) ml/g/h. The results presented here clearly indicate that this proposed method could be applicable to investigate the pharmacokinetic of phenazopyridine in rats after administration. (c) PMID- 17847065 TI - Unilateral focal polymicrogyria in a patient with classical Aarskog-Scott syndrome due to a novel missense mutation in an evolutionary conserved RhoGEF domain of the faciogenital dysplasia gene FGD1. AB - Faciogenital dysplasia or Aarskog-Scott syndrome (AAS) is an X-linked disorder characterized by craniofacial, skeletal, and urogenital malformations and short stature. Mutations in the only known causative gene FGD1 are found in about one fifth of the cases with the clinical diagnosis of AAS. FGD1 is a guanine nucleotide exchange factor (GEF) that specifically activates the Rho GTPase Cdc42 via its RhoGEF domain. The Cdc42 pathway is involved in skeletal formation and multiple aspects of neuronal development. We describe a boy with typical AAS and, in addition, unilateral focal polymicrogyria (PMG), a feature hitherto unreported in AAS. Sequencing of the FGD1 gene in the index case and his mother revealed the presence of a novel mutation (1396A>G; M466V), located in the evolutionary conserved alpha-helix 4 of the RhoGEF domain. M466V was not found in healthy family members, in >300 healthy controls and AAS patients, and has not been reported in the literature or mutation databases to date, indicating that this novel missense mutation causes AAS, and possibly PMG. Brain cortex malformations such as PMG could be initiated by mutations in the evolutionary conserved RhoGEF domain of FGD1, by perturbing the signaling via Rho GTPases such as Cdc42 known to cause brain malformation. PMID- 17847066 TI - Associated malformations in patients with oral clefts. PMID- 17847067 TI - Characterization of ternary solid dispersions of itraconazole, PEG 6000, and HPMC 2910 E5. AB - In order to reduce the crystallinity of PEG 6000, blends were prepared by spray drying and extrusion with the following polymers; PVP K25, PVPVA 64, and HPMC 2910 E5. The maximal reduction of crystallinity in PEG 6000 was obtained by co spray drying with HPMC 2910 E5. In the next step the model drug Itraconazole was added to the blend and the resulting ternary solid dispersions were characterized. The results of this study show that the addition of PEG 6000 to the Itraconazole/HPMC 2910 E5 system leads to phase separation that in most cases gives rise to recrystallization of either PEG 6000 or Itraconazole. For all ternary dispersions containing 20% of Itraconazole the drug was highly amorphous and the dissolution was improved compared to the binary 20/80 w/w Itraconazole/HPMC 2910 E5 solid dispersion. For all ternary dispersions containing 40% of Itraconazole, the drug was partially crystalline and the dissolution was lower than the dissolution of the binary 40/60 w/w Itraconazole/HPMC 2910 E5 dispersion. These results show that provided Itraconazole is highly amorphous the addition of PEG 6000 to HPMC 2910 E5 leads to an increase in drug release. PMID- 17847068 TI - Metabolic bioactivation and toxicity of ethyl 4-hydroxybenzoate in human SK-MEL 28 melanoma cells. AB - The metabolism and toxicity of ethyl 4-hydroxybenzoate (4-HEB) were investigated in vitro using tyrosinase enzyme, a melanoma molecular target, and CYP2E1 induced rat liver microsomes, and in human SK-MEL-28 melanoma cells. The results were compared to 4-hydroxyanisole (4-HA). At 90 min, 4-HEB was metabolized 48% by tyrosinase and 26% by liver microsomes while the extent of 4-HA metabolism was 196% and 88%, respectively. The IC50 (day 2) of 4-HEB and 4-HA towards SK-MEL-28 cells were 75 and 50 microM, respectively. Dicoumarol, a diaphorase inhibitor, and 1-bromoheptane, a GSH depleting agent, increased 4-HEB toxicity towards SK MEL-28 cells indicating o-quinone formation played an important role in 4-HEB induced cell toxicity. Addition of ascorbic acid and GSH to the media was effective in preventing 4-HEB cell toxicity. Cyclosporin A and trifluoperazine, inhibitors of permeability transition pore in mitochondria, were significantly potent in inhibiting 4-HEB cell toxicity. 4-HEB caused time-dependent decline in intracellular GSH concentration which preceded cell death. 4-HEB also led to reactive oxygen species (ROS) formation in melanoma cells which exacerbated by dicoumarol and 1-bromoheptane whereas cyclosporin A and trifluoperazine prevented it. Our findings suggest that the mechanisms of 4-HEB toxicity in SK-MEL-28 were o-quinone formation, intracellular GSH depletion, ROS formation and mitochondrial toxicity. PMID- 17847069 TI - Effect of anesthetic structure on inhalation anesthesia: implications for the mechanism. AB - Many previous attempts (e.g., the Meyer-Overton hypothesis) to provide a single set of physical or chemical characteristics that accurately predict anesthetic potency have failed. A finding of a general predictive correlation would support the notion of a unitary theory of narcosis. Using the Abraham solvation parameter model, the minimum alveolar concentration, MAC, of 148 varied anesthetic agents can be fitted to a linear equation in log (1/MAC) with R(2) = 0.985 and a standard deviation, SD = 0.192 log units. Division of the 148 compounds into a training set and a test set shows that log (1/MAC) values can be predicted with no bias and with SD = 0.20 log units. The two main factors that determine MAC values are compound size and compound hydrogen bond acidity, both of which increase anesthetic activity. Shape has little or no effect on anesthetic activity. Our observations support a unitary theory of narcosis by inhalation anesthetics. A two-stage mechanism for inhalation anesthesia accounts for the observed structural effects of anesthetics. In this mechanism, the first main step is transfer of the anesthetic to the site of action, and the second step is interaction of the anesthetic with a receptor(s). PMID- 17847070 TI - Quantification of normal range of inflammatory changes in morphologically normal pediatric muscle. AB - The aim of this study was to define normal ranges of histological features in pediatric muscle in comparison with muscle demonstrating inflammatory changes. Sixteen pediatric muscle biopsy samples, considered normal by standard histology, were analyzed for the presence of inflammatory cells, and the expression of neonatal myosin and major histocompatibility complex (MHC) Class 1. Normal findings were defined for each feature. These data will facilitate quantitative analysis of inflammatory changes in pediatric muscle biopsy. PMID- 17847071 TI - Systematic studies on the paracellular permeation of model permeants and oligonucleotides in the rat small intestine with chenodeoxycholate as enhancer. AB - The objective of this study was to mechanistically and quantitatively analyze chenodeoxycholate-enhanced paracellular transport of polar permeants and oligonucleotides in the rat jejunum and ileum. Micellar chenodeoxycholate solutions were used to perturbate the tight junctions. Supporting studies included assessment of the aqueous boundary layer (ABL) with ABL-controlled permeants, measurements of the permeability coefficients and fluxes of the bile acid in dilute and micellar concentrations, and determinations of pore sizes with paracellular probes (urea, mannitol, and raffinose). The paracellular permeability coefficients, P(para), of two model oligonucleotides (ON3 and ON6; 12- and 24-mers with 11 and 23 negative charges, respectively) were determined. The enhanced permeabilities paralleled the increased fluxes of micellar bile salt solutions into mesenteric blood and the opening of the tight junctions as compared to controls. As the pore radius increased from 0.7 nm to a maximum of 2.4 nm in the jejunum and ileum, the absorption of ON3 was enhanced up to sixfold in the jejunum and about 14-fold in the ileum with P(para) values between 0.5 x 10(-6) and 6 x 10(-6) cm/s, whereas ON6 was enhanced up to twofold in the jejunum and fivefold in the ileum with permeabilities between 0.3 x 10(-6) and 2 x 10(-6) cm/s. PMID- 17847072 TI - Endotoxin limits in formulations for preclinical research. AB - This brief commentary discusses a review of the current status on endotoxin limits, a critical parameter, for formulations to be administered to animals. The endotoxin units set by United States Pharmacopoeia (USP), and the techniques specified by USP for endotoxin testing are described. Endotoxin limits for preclinical research animal models were derived based on the threshold pyrogenic human dose of 5 E.U. per kg. The limits calculated would act as a guideline for endotoxin limits in preclinical species. A quick reference chart for endotoxin limits is included to provide a guideline for endotoxin limits for animal models used in preclinical research. Derivation of endotoxin limits from K/M for doses and animal models not included in the chart could be calculated as described. PMID- 17847073 TI - Solvent diversity in polymorph screening. AB - Selecting a diverse set of solvents to be included in polymorph screening assignments can be a challenging task. As an aid to decision making, a database of 218 organic solvents with 24 property descriptors was explored and visualized using multivariate tools. The descriptors included, among others, log P, vapor pressure, hydrogen bond formation capabilities, polarity, number of pi-bonds and descriptors derived from molecular interaction field calculations (e.g., size/shape parameters and hydrophilic/hydrophobic regions). The data matrix was initially analyzed using principal component analysis (PCA). Results from the PCA showed 57% cumulative variance being explained in the first two principal components (PCs), although relevant information was also found in the third, fourth and fifth component, revealing distinct clusters of solvents. Since five dimensions were not suitable for visual presentation, a nonlinear method, self organizing maps (SOMs), was applied to the dataset. The constructed SOM displayed features of clusters observed in the first three PCs, however in a more compelling way. Thus, the SOM was chosen as the visually most convenient way to display the diversity of the 218 solvents. In addition, it was demonstrated how safety aspects can be considered by labeling a large fraction of the solvents in the SOM with toxicological information. PMID- 17847074 TI - Association of human APOBEC3 cytidine deaminases with the generation of hepatitis virus B x antigen mutants and hepatocellular carcinoma. AB - Human APOBEC3 (apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3) cytidine deaminases have been shown to be potent inhibitors of diverse retroviruses including Vif-deficient human immunodeficiency virus 1 (HIV-1), hepatitis virus B (HBV), adeno-associated virus, and endogenous retroelements. Despite the fact that these enzymes are known to be potential DNA mutators and to target retroviral DNA for cytidine deamination, the pathological effects of their deregulated expression in human diseases are not yet clear. Mutants of the viral HBx protein have been implicated in the carcinogenesis of hepatocellular carcinoma (HCC); however, little is known about how or why such mutants are generated in the human liver. Here, we report that a number of APOBEC3 deaminases preferentially edit the HBx region of HBV DNA and generate C-terminally truncated HBx mutants. Our functional studies indicated that APOBEC3-mediated HBx mutants, especially the C-terminally truncated mutants, cause a gain of function that enhances the colony-forming ability and proliferative capacity of neoplastic cells. Furthermore, we detected G-to-A hypermutation-mediated HBx mutants in preneoplastic liver tissues of selected patients with active chronic HBV infections. We also observed that the APOBEC3B (A3B) cytidine deaminase was widely up-regulated in HCC tumor tissues; it also promoted the growth of neoplastic human HepG2 liver cells and up-regulated heat shock transcription factor1 (HSF1) expression. CONCLUSION: These findings suggest that some of the APOBEC3 deaminases play a role in the carcinogenesis of HCC through the generation of HBx mutants, providing preneoplastic and neoplastic hepatocytes with a selective clonal growth advantage. Deregulated expression of A3B in liver tissues may also have the potential to promote genetic instability and tumorigenesis. PMID- 17847075 TI - Oral and IV dosing: a method to determine the compartment of drug elimination for two-compartment models. AB - It has been shown previously that it is impossible to measure the volume of distribution at steady state conclusively for a multicompartment system from an iv bolus dose only. The problem lies in deciding from which compartment elimination of the drug occurs in the compartmental model. In this paper a new modelling strategy is examined whereby the compartment of elimination may be identified uniquely for the case of two-compartment models. The two models examined predict different profiles in the absorption phase of an oral profile. An in vivo data set is provided that favours a peripheral elimination explanation of its observed pharmacokinetics, based on the 'goodness of fit'. PMID- 17847076 TI - Raman spectroscopy of protein pharmaceuticals. AB - Recent advances in optical and spectroscopic technologies have enabled a plethora of Raman spectrometers that are suitable for studies of protein pharmaceuticals. Highly sensitive Raman spectrometers have overcome the handicap of the fundamentally weak Raman effect that hampered their applications to protein pharmaceuticals in the past. These Raman spectrometers can now routinely measure protein therapeutics at the low concentration of 1 mg/mL, which is on par with other spectroscopic methods such as CD, fluorescence and FTIR spectroscopies. In this article, various Raman techniques that can be used for protein pharmaceutical studies are reviewed. Novel Raman marker of proteins discovered from fundamental studies of protein complexes are examined along with established Raman spectra and structure correlations. Examples of Raman spectroscopic studies of protein pharmaceuticals are demonstrated. Future applications of Raman spectroscopy to protein pharmaceuticals are discussed. PMID- 17847077 TI - Polymer implants for intratumoral drug delivery and cancer therapy. AB - To address the need for minimally invasive treatment of unresectable tumors, intratumoral polymer implants have been developed to release a variety of chemotherapeutic agents for the locoregional therapy of cancer. These implants, also termed "polymer millirods," were designed to provide optimal drug release kinetics to improve drug delivery efficiency and antitumor efficacy when treating unresectable tumors. Modeling of drug transport properties in different tissue environments has provided theoretical insights on rational implant design, and several imaging techniques have been established to monitor the local drug concentrations surrounding these implants both ex vivo and in vivo. Preliminary antitumor efficacy and drug distribution studies in a rabbit liver tumor model have shown that these implants can restrict tumor growth in small animal tumors (diameter < 1 cm). In the future, new approaches, such as three-dimensional (3-D) drug distribution modeling and the use of multiple drug-releasing implants, will be used to extend the efficacy of these implants in treating larger tumors more similar to intractable human tumors. PMID- 17847078 TI - Presynaptic evidence for zinc release at the mossy fiber synapse of rat hippocampus. AB - Vesicular zinc (Zn(2+)) is found in a subset of glutamatergic nerve terminals throughout the mammalian forebrain and is colocalized with glutamate. Despite well-documented neuromodulatory roles, exocytosis of endogenous Zn(2+) from presynaptic terminals has never been directly demonstrated, because existing studies have measured elevated Zn(2+) concentrations by examining the perfusate. Thus, the specific origin of synaptic Zn(2+) remains a controversial subject. Here, we describe synaptic Zn(2+) trafficking between cellular compartments at hippocampal mossy fiber synapses by using the fluorescent indicator Zinpyr-1 to label the hippocampal mossy fiber boutons. We determined endogenous Zn(2+) exocytosis by direct observation of vesicular Zn(2+) as decreasing fluorescence intensity from presynaptic axonal boutons in the stratum lucidum of CA3 during neural activities induced by the stimulation of membrane depolarization. This presynaptic fluorescence gradually returned to a level near baseline after the withdrawal of moderate stimulation, indicating an endogenous mechanism to replenish vesicular Zn(2+). The exocytosis of the synaptic Zn(2+) was also dependent on extracellular Ca(2+) and was sensitive to Zn(2+)-specific chelators. Vesicular Zn(2+) loading was sensitive to the vacuolar-type H(+)-ATPase inhibitor concanamycin A, and our experiments indicated that blockade of vesicular reloading with concanamycin A led to a depletion of that synaptic Zn(2+). Furthermore, synaptic Zn(2+) translocated to the postsynaptic cell body upon release to produce increases in the concentration of weakly bound Zn(2+) within the postsynaptic cytosol, demonstrating a feature unique to ionic substances released during neurotransmission. Our data provide important evidence for Zn(2+) as a substance that undergoes release in a manner similar to common neurotransmitters. PMID- 17847079 TI - Chemokine receptors and neurotrophic factors: potential therapy against aids dementia? AB - Chemokine receptors, in particular, CXCR4 and CCR5, mediate human immunodeficiency virus type 1 (HIV-1) infection of immunocompetent cells and the apoptosis of these cells. However, the virus does not infect neurons. Yet through a variety of mechanisms, HIV promotes glial cell activation, synaptodendritic alterations, and neuronal loss that ultimately lead to motor and cognitive impairment. Chemokines and chemokine receptors are abundant in the adult central nervous system and play a role in neuronal apoptosis evoked by HIV proteins. Thus, reducing the availability of chemokine receptors may prevent the neuronal degeneration seen in HIV-positive patients. In this article, we present and discuss a recent experimental approach aimed at testing effective neuroprotective therapies against HIV-mediated neuronal degeneration. PMID- 17847080 TI - Relationship between ribosomal RNA gene transcription activity and motoneuron death: observations of avulsion and axotomy of the facial nerve in rats. AB - Motoneuron number and expression of cytoplasmic RNA and ribosomal RNA (rRNA) gene transcription activity in the facial nucleus were examined quantitatively and chronologically for up to 4 weeks in rats after facial nerve axotomy and avulsion in order to elucidate interrelationships in axonal changes. The right facial nerves of adult Fischer rats were avulsed at a portion of the outlet or axotomized at a portion of the foramen stylomastoideus. The number of large motoneurons in the facial nucleus was reduced by 40% 2 weeks after avulsion and by 70% 4 weeks after avulsion but displayed a 19% loss even 4 weeks after axotomy. The amount of cytoplasmic RNA decreased significantly and progressively from 1 day after avulsion. rRNA gene transcription activity in the large motoneurons of the facial nucleus decreased significantly beginning 30 min after both axotomy and avulsion, but the severity of the decrease was far more marked in the avulsion group, showing a 59% loss from the control value 4 weeks after avulsion. These findings indicate that rRNA gene transcription activity, expression of cytoplasmic RNA, and the number of motoneurons that survive are interrelated and that the decrease in rRNA gene transcription activity is a very early event in the phenomena observed in the axonal reactions of motoneurons. PMID- 17847082 TI - Mitochondrial transport proteins of the brain. AB - In this study, cellular distribution and activity of glutamate and gamma aminobutyric acid (GABA) transport as well as oxoglutarate transport across brain mitochondrial membranes were investigated. A goal was to establish cell-type specific expression of key transporters and enzymes involved in neurotransmitter metabolism in order to estimate neurotransmitter and metabolite traffic between neurons and astrocytes. Two methods were used to isolate brain mitochondria. One method excludes synaptosomes and the organelles may therefore be enriched in astrocytic mitochondria. The other method isolates mitochondria derived from all regions of the brain. Immunological and enzymatic methods were used to measure enzymes and carriers in the different preparations, in addition to studying transport kinetics. Immunohistochemistry was also employed using brain slices to confirm cell type specificity of enzymes and carriers. The data suggest that the aspartate/glutamate carriers (AGC) are expressed predominantly in neurons, not astrocytes, and that one of two glutamate/hydroxyl carriers is expressed predominantly in astrocytes. The GABA carrier and the oxoglutarate carrier appear to be equally distributed in astrocytes and neurons. As expected, pyruvate carboxylase and branched-chain aminotransferase were predominantly astrocytic. Insofar as the aspartate/glutamate exchange carriers are required for the malate/aspartate shuttle and for reoxidation of cytosolic NADH, the data suggest a compartmentation of glucose metabolism in which astrocytes catalyze glycolytic conversion of glucose to lactate, whereas neurons are capable of oxidizing both lactate and glucose to CO(2) + H(2)O. PMID- 17847083 TI - Expression of the scaffolding PDZ protein glutaminase-interacting protein in mammalian brain. AB - A human brain cDNA clone coding for a novel PDZ-domain protein of 124 amino acids was previously isolated in our laboratory. The protein was termed glutaminase interacting protein (GIP), because it interacts with the C-terminal region of the human L-type glutaminase (LGA). The pattern of expression and functions of GIP in brain are completely unknown, so its significance remains undefined. Here we describe the expression of GIP mRNA and protein in mammalian brain. Northern blot analysis revealed that GIP mRNA was ubiquitous in most regions of human brain but was particularly abundant in spinal cord. The presence of the protein in rat and monkey brain was studied at the regional, cellular, and subcellular level by immunocytochemistry. The protein was found to be present in both neurons and astrocytes, with a cytosolic and mitochondrial subcellular localization. Double immunofluorescence labeling with anti-GIP and anti-LGA antibodies using confocal microscopy revealed colocalization of both proteins in astrocyte cell processes and their perivascular end feet. Electron microscopy of rat brain neurons revealed GIP immunoreactivity concentrated also in the nuclear envelope and the plasma membrane. The multiple locations for GIP in mammalian brain are in agreement with known protein interaction partners reported for this PDZ protein. The findings presented here support a role of GIP as an important scaffold in both astrocytes and neurons and point toward astrocytic processes and perivascular end feet as plausible anatomical substrates for interaction with glutaminase. PMID- 17847081 TI - Mechanisms of impaired mitochondrial energy metabolism in acute and chronic neurodegenerative disorders. AB - Altered mitochondrial energy metabolism contributes to the pathophysiology of acute brain injury caused by ischemia, trauma, and neurotoxins and by chronic neurodegenerative disorders such as Parkinson's and Huntington's diseases. Although much evidence supports that the electron transport chain dysfunction in these metabolic abnormalities has both genetic and intracellular environmental causes, alternative mechanisms are being explored. These include direct, reversible inhibition of cytochrome oxidase by nitric oxide, release of mitochondrial cytochrome c, oxidative inhibition of mitochondrial matrix dehydrogenases and adenine nucleotide transport, the availability of NAD for dehydrogenase reactions, respiratory uncoupling by activities such as that of the permeability transition pore, and altered mitochondrial structure and intracellular trafficking. This review focuses on the catabolism of neuronal NAD and the release of neuronal mitochondrial NAD as important contributors to metabolic dysfunction. In addition, the relationship between apoptotic signaling cascades and disruption of mitochondrial energy metabolism is considered in light of the fine balance between apoptotic and necrotic neural cell death. PMID- 17847084 TI - Structure of aspartate racemase complexed with a dual substrate analogue, citric acid, and implications for the reaction mechanism. AB - Pyrococcus horikoshii OT3 aspartate racemase (PhAspR) catalyzes the interconversion between L- and D-aspartate. The X-ray structure of PhAspR revealed a pseudo mirror-symmetric distribution of the residues around its active site, which is very reasonable for its chiral substrates, L-aspartate and D aspartate. In this study, we have determined the crystal structure of an inactive mutant PhAspR complexed with a citric acid (Cit) at a resolution of 2.0 A. Cit contains the substrate analogue moieties of both L- and D-aspartate and exhibits a low competitive inhibition activity against PhAspR. In the structure, Cit binds to the catalytic site of PhAspR, which induced the conformational change to close the active site. The distance between the thiolates was estimated to be 7.4 A, representing a catalytic state and the substrate binding modes of PhAspR. Two conserved basic residues, Arg48 and Lys164, seem to be indispensable for PhAspR activity. Arg48 is thought to be responsible for recognizing carboxyl groups of the substrates L-/D-aspartates and stabilizing a reaction intermediate, and Lys164 is responsible for stabilizing a closed state structure. In this structure, the L-aspartate moiety of Cit is likely to take the substrate position of the PhAspR-substrate complex, which is very similar to that of Glutamate racemase. There is also another possibility that the two substrate analogue moieties of the bound Cit reflect the binding modes of both L- and D-aspartates. Based on the PhAspR-Cit complex structure, the reaction mechanism of aspartate racemase was elucidated. PMID- 17847085 TI - Epitope mapping and structural analysis of an anti-ErbB2 antibody A21: Molecular basis for tumor inhibitory mechanism. AB - Anti-ErbB2 antibodies targeting distinct epitopes can have different biological functions on cancer cells. A21 prepared by surface epitope masking (SEM) method is a tumor-inhibitory anti-ErbB2 monoclonal antibody. Previously we engineered a single chain chimeric antibody chA21 with potential for therapy of ErbB2 overexpressing tumors. Here, we mapped the A21 epitope on ErbB2 extracellular domain (ECD) by screening a combinatorial phage display peptide library, serial subdomain deletion, and mutagenesis scanning. X-ray crystal structure of the A21 scFv fragment at 2.1 A resolution was also determined. A molecular model of Ag-Ab complex was then constructed based on the crystal structures of the A21 scFv and ErbB2 ECD. Some of biological functions of the A21 mAb and its derivative antibodies including their tumor cell growth inhibition and effects on the expression, internalization, and phosphorylation of ErbB2 receptor were also investigated. The results showed that A21 recognized a conformational epitope comprising a large region mostly from ErbB2 extracellular subdomain I with several surface-exposed residues important for the binding affinity. These data provide unique functional properties of A21 that are quite different from two broadly used anti-ErbB2 mAbs, Herceptin and 2C4. It suggested that the A21 epitope may be another valuable target for designing new anti-ErbB2 therapeutics. PMID- 17847086 TI - Water penetration in the low and high pressure native states of ubiquitin. AB - Theoretical studies on the solvation of methane molecules in water have shown that the effect of increased pressure is to stabilize solvent separated contacts relative to direct contacts. This suggests that high pressure stabilizes waters that have penetrated into a protein's core, indicating a mechanism for the high pressure denaturation of proteins. We test this theory on a folded protein by studying the penetration of water into the native state of ubiquitin at low and high pressures, using molecular dynamics. An ensemble of conformations sampled in the folded state of ubiquitin has been determined by NMR at two pressures below the protein's denaturation pressure, 30 atm and 3000 atm. We find that 1-5 more waters penetrate the high pressure conformations than the low pressure conformations. Low volume configurations of the system are favored at high pressures, but different components of the system may experience increases or decreases in their specific volumes. We find that penetrating waters have a higher volume per water than bulk waters, but that the volume per protein residue may be lowered by solvation. Furthermore, we find that penetration of the protein by water at high pressures is driven by the difference in the pressure dependence of the probability of cavity opening in the protein and pressure dependence of the probability of cavity opening in the bulk solvent. The volume changes associated with cavity opening and closing indicate that each penetrating water reduces the volume of the system by about 12 mL/mol. The experimental volume change going from the low pressure to the high pressure native state of ubiquitin is 24 mL/mol. Our results indicate that this volume change can be explained by penetration of the protein by two water molecules. PMID- 17847087 TI - Conformational flexibility in mammalian 15S-lipoxygenase: Reinterpretation of the crystallographic data. AB - Lipoxygenases (LOXs) are a family of nonheme iron dioxygenases that catalyze the regioselective and stereospecific hydroperoxidation of polyunsaturated fatty acids, and are involved in a variety of inflammatory diseases and cancers. The crystal structure of rabbit 15S-LOX1 that was reported by Gillmor et al. in 1997 has played key roles for understanding the properties of mammalian LOXs. In this structure, three segments, including 12 residues in the superficial alpha2 helix, are absent and have usually been described as "disordered." By reinterpreting the original crystallographic data we were able to elucidate two different conformations of the molecule, both having well ordered alpha2 helices. Surprisingly, one molecule contained an inhibitor and the other did not, thereby adopting a closed and an open form, respectively. They differed in the conformation of the segments that were absent in the original structure, which is highlighted by a 12 A movement of alpha2. Consequently, they showed a difference in the size and shape of the substrate-binding cavity. The new model should provide new insight into the catalytic mechanism involving induced conformational change of the binding pocket. It may also be helpful for the structure-based design of LOX inhibitors. PMID- 17847088 TI - Distance dependent centroid to centroid force fields using high resolution decoys. AB - Simplified force fields play an important role in protein structure prediction and de novo protein design by requiring less computational effort than detailed atomistic potentials. A side chain centroid based, distance dependent pairwise interaction potential has been developed. A linear programming based formulation was used in which non-native "decoy" conformers are forced to take a higher energy compared with the corresponding native structure. This model was trained on an enhanced and diverse protein set. High quality decoy structures were generated for approximately 1400 nonhomologous proteins using torsion angle dynamics along with restricted variations of the hydrophobic cores of the native structure. The resulting decoy set was used to train the model yielding two different side chain centroid based force fields that differ in the way distance dependence has been used to calculate energy parameters. These force fields were tested on an independent set of 148 test proteins with 500 decoy structures for each protein. The side chain centroid force fields were successful in correctly identifying approximately 86% native structures. The Z-scores produced by the proposed centroid-centroid distance dependent force fields improved compared with other distance dependent C(alpha)-C(alpha) or side chain based force fields. PMID- 17847089 TI - Exploiting 3D structural templates for detection of metal-binding sites in protein structures. AB - High throughput structural genomics efforts have been making the structures of proteins available even before their function has been fully characterized. Therefore, methods that exploit the structural knowledge to provide evidence about the functions of proteins would be useful. Such methods would be needed to complement the sequence-based function annotation approaches. The current study describes generation of 3D-structural motifs for metal-binding sites from the known metalloproteins. It then scans all the available protein structures in the PDB database for putative metal-binding sites. Our analysis predicted more than 1000 novel metal-binding sites in proteins using three-residue templates, and more than 150 novel metal-binding sites using four-residue templates. Prediction of metal-binding site in a yeast protein YDR533c led to the hypothesis that it might function as metal-dependent amidopeptidase. The structural motifs identified by our method present novel metal-binding sites that reveal newer mechanisms for a few well-known proteins. PMID- 17847090 TI - Molecular docking study of the interactions between the thioesterase domain of human fatty acid synthase and its ligands. AB - Human fatty acid synthase (hFAS) thioesterase domain (TE) is an attractive drug target to treat obesity and cancer. On the basis of the recently published crystal structure of TE domain of hFAS, we performed molecular surface analysis and docking study to characterize the molecular interactions between the enzyme and its various ligands. Surface analysis identified the ligand-binding pocket of TE domain that encompasses the catalytic triad of Ser2308, His2481, Asp2338. Docking of palmitate, the main biological product of hFAS, into this pocket revealed the ligand-binding mode, in which the hydrophobic interactions are the dominant driving forces. The catalytic mechanism of TE domain can also be well explained based on the generated TE-palmitate complex structure. Moreover, the comparison of the binding modes of five fatty acids with chain lengths ranging from 12 to 20 carbons confirmed that the ligand binding pocket of TE domain is a decisive factor in chain length specificity. In addition, docking of two known TE inhibitors, c75 and orlistat revealed the pharmacophore of these hFAS TE inhibitors, which will prove useful in structure-based drug design against this important target. PMID- 17847091 TI - Native atomic burials, supplemented by physically motivated hydrogen bond constraints, contain sufficient information to determine the tertiary structure of small globular proteins. AB - We investigate the possibility that atomic burials, as measured by their distances from the structural geometrical center, contain sufficient information to determine the tertiary structure of globular proteins. We report Monte Carlo simulated annealing results of all-atom hard-sphere models in continuous space for four small proteins: the all-beta WW-domain 1E0L, the alpha/beta protein-G 1IGD, the all-alpha engrailed homeo-domain 1ENH, and the alpha + beta engineered monomeric form of the Cro protein 1ORC. We used as energy function the sum over all atoms, labeled by i, of |R(i) - R(i) (*)|, where R(i) is the atomic distance from the center of coordinates, or central distance, and R(i) (*) is the "ideal" central distance obtained from the native structure. Hydrogen bonds were taken into consideration by the assignment of two ideal distances for backbone atoms forming hydrogen bonds in the native structure depending on the formation of a geometrically defined bond, independently of bond partner. Lowest energy final conformations turned out to be very similar to the native structure for the four proteins under investigation and a strong correlation was observed between energy and distance root mean square deviation (DRMS) from the native in the case of all beta 1E0L and alpha/beta 1IGD. For all alpha 1ENH and alpha + beta 1ORC the overall correlation between energy and DRMS among final conformations was not as high because some trajectories resulted in high DRMS but low energy final conformations in which alpha-helices adopted a non-native mutual orientation. Comparison between central distances and actual accessible surface areas corroborated the implicit assumption of correlation between these two quantities. The Z-score obtained with this native-centric potential in the discrimination of native 1ORC from a set of random compact structures confirmed that it contains a much smaller amount of native information when compared to a traditional contact Go potential but indicated that simple sequence-dependent burial potentials still need some improvement in order to attain a similar discriminability. Taken together, our results suggest that central distances, in conjunction to physically motivated hydrogen bond constraints, contain sufficient information to determine the native conformation of these small proteins and that a solution to the folding problem for globular proteins could arise from sufficiently accurate burial predictions from sequence followed by minimization of a burial-dependent energy function. PMID- 17847092 TI - Kinetic analysis of molecular dynamics simulations reveals changes in the denatured state and switch of folding pathways upon single-point mutation of a beta-sheet miniprotein. AB - The effects of a single-point mutation on folding thermodynamics and kinetics are usually interpreted by focusing on the native structure and the transition state. Here, the entire conformational spaces of a 20-residue three-stranded antiparallel beta-sheet peptide (double hairpin) and of its single-point mutant W10V are sampled close to the melting temperature by equilibrium folding unfolding molecular dynamics simulations for a total of 40 micros. The folded state as well as the most populated free energy basins in the denatured state are isolated by grouping conformations according to fast relaxation at equilibrium. Such kinetic analysis provides more detailed and useful information than a simple projection of the free energy. The W10V mutant has the same native structure as the wild type peptide, and similar folding rate and stability. In the denatured state, the N-terminal hairpin is about 20% more structured in W10V than the wild type mainly because of van der Waals interactions. Notably, the W10V mutation influences also the van der Waals energy at the transition state ensemble causing a shift in the ratio of fluxes between two different transition state regions on parallel folding pathways corresponding to nucleation at either of the two beta hairpins. Previous experimental studies have focused on the effects of denaturant dependent or temperature-dependent changes in the structure of the denatured state. The atomistic simulations show that a single-point mutation in the central strand of a beta-sheet peptide results in remarkable changes in the topography of the denatured state ensemble. These changes modulate the relative accessibility of parallel folding pathways because of kinetic partitioning of the denatured state. Therefore, the observed dependence of the folding process on the starting ensemble raises questions on the biological significance of in vitro folding studies under strongly denaturing conditions. PMID- 17847093 TI - Proton pathways in a [NiFe]-hydrogenase: A theoretical study. AB - We present here a theoretical study to investigate possible proton pathways in the [NiFe]-hydrogenase from Desulfovibrio gigas. The approach used in this study consists of a combination of Poisson-Boltzmann and Monte Carlo simulations together with a distance-based network analysis to find possible groups involved in the proton transfer. Results obtained at different pH values show a reasonable number of proton active residues distributed by the protein interior and surface, with a concentration around the metal centres. The electrostatic interactions in this protein are strong, as shown by the unusual shape of the titration curves of several sites. Some residue pairs show strongly correlated protonations, indicating the sharing and probably exchange of a proton between them. The conjugation of the PB and MC simulations with the distance-based analysis allows a detailed characterization of the possible proton pathways. We discuss previous suggestions and propose a new complete pathway for the proton transfer between the active site and the surface. This pathway is mainly composed of histidines and glutamic acid residues. PMID- 17847094 TI - Dopamine transporter comparative molecular modeling and binding site prediction using the LeuT(Aa) leucine transporter as a template. AB - Pharmacological and behavioral studies indicate that binding of cocaine and the amphetamines by the dopamine transporter (DAT) protein is principally responsible for initiating the euphoria and addiction associated with these drugs. The lack of an X-ray crystal structure for the DAT or any other member of the neurotransmitter:sodium symporter (NSS) family has hindered understanding of psychostimulant recognition at the atomic level; structural information has been obtained largely from mutagenesis and biophysical studies. The recent publication of a crystal structure for the bacterial leucine transporter LeuT(Aa), a distantly related NSS family homolog, provides for the first time a template for three-dimensional comparative modeling of NSS proteins. A novel computational modeling approach using the capabilities of the Molecular Operating Environment program MOE 2005.06 in conjunction with other comparative modeling servers generated the LeuT(Aa)-directed DAT model. Probable dopamine and amphetamine binding sites were identified within the DAT model using multiple docking approaches. Binding sites for the substrate ligands (dopamine and amphetamine) overlapped substantially with the analogous region of the LeuT(Aa) crystal structure for the substrate leucine. The docking predictions implicated DAT side chains known to be critical for high affinity ligand binding and suggest novel mutagenesis targets in elucidating discrete substrate and inhibitor binding sites. The DAT model may guide DAT ligand QSAR studies, and rational design of novel DAT-binding therapeutics. PMID- 17847095 TI - Protonless 13C direct detection NMR: characterization of the 37 kDa trimeric protein CutA1. AB - The major limitation of nuclear magnetic resonance spectroscopy arises from the increase of nuclear transverse relaxation rates with increasing molecular mass. This causes reduction in spectral resolution and coherence transfer efficiency. The use of 2H-labeling to eliminate 1H-mediated relaxation pathways and the constructive use of cross correlation effects (TROSY, CRINEPT) alleviate the phenomenon. An alternative approach is to use direct detection of heteronuclei. Specifically designed 13C direct detection experiments can complement the set of 1H-based NMR experiments commonly used for structure determination providing an additional source of information less affected by the detrimental transverse relaxation effect. We applied this novel methodology to the study of the CutA1 protein (12.3 kDa) from E. coli that forms a homotrimer in solution with a total molecular mass of 37 kDa. In this work we demonstrate that the information available from 13C direct detection experiments makes it possible to completely assign the NMR resonances of the backbone of this 37 kDa trimeric protein without the need of deuteration. The structural and dynamical knowledge obtained for this system may contribute to understand its biological role. PMID- 17847096 TI - Predicting transmembrane helix pair configurations with knowledge-based distance dependent pair potentials. AB - As a first step toward a novel de novo structure prediction approach for alpha helical membrane proteins, we developed coarse-grained knowledge-based potentials to score the mutual configuration of transmembrane (TM) helices. Using a comprehensive database of 71 known membrane protein structures, pairwise potentials depending solely on amino acid types and distances between C(alpha) atoms were derived. To evaluate the potentials, they were used as an objective function for the rigid docking of 442 TM helix pairs. This is by far the largest test data set reported to date for that purpose. After clustering 500 docking runs for each pair and considering the largest cluster, we found solutions with a root mean squared (RMS) deviation <2 A for about 30% of all helix pairs. Encouragingly, if only clusters that contain at least 20% of all decoys are considered, a success rate >71% (with a RMS deviation <2 A) is obtained. The cluster size thus serves as a measure of significance to identify good docking solutions. In a leave-one-protein-family-out cross-validation study, more than 2/3 of the helix pairs were still predicted with an RMS deviation <2.5 A (if only clusters that contain at least 20% of all decoys are considered). This demonstrates the predictive power of the potentials in general, although it is advisable to further extend the knowledge base to derive more robust potentials in the future. When compared to the scoring function of Fleishman and Ben-Tal, a comparable performance is found by our cross-validated potentials. Finally, well predicted "anchor helix pairs" can be reliably identified for most of the proteins of the test data set. This is important for an extension of the approach towards TM helix bundles because these anchor pairs will act as "nucleation sites" to which more helices will be added subsequently, which alleviates the sampling problem. PMID- 17847097 TI - Structural and enzymatic characterization of DR1281: A calcineurin-like phosphoesterase from Deinococcus radiodurans. AB - We have determined the crystal structure of DR1281 from Deinococcus radiodurans. DR1281 is a protein of unknown function with over 170 homologs found in prokaryotes and eukaryotes. To elucidate the molecular function of DR1281, its crystal structure at 2.3 A resolution was determined and a series of biochemical screens for catalytic activity was performed. The crystal structure shows that DR1281 has two domains, a small alpha domain and a putative catalytic domain formed by a four-layered structure of two beta-sheets flanked by five alpha helices on both sides. The small alpha domain interacts with other molecules in the asymmetric unit and contributes to the formation of oligomers. The structural comparison of the putative catalytic domain with known structures suggested its biochemical function to be a phosphatase, phosphodiesterase, nuclease, or nucleotidase. Structural analyses with its homologues also indicated that there is a dinuclear center at the interface of two domains formed by Asp8, Glu37, Asn38, Asn65, His148, His173, and His175. An absolute requirement of metal ions for activity has been proved by enzymatic assay with various divalent metal ions. A panel of general enzymatic assays of DR1281 revealed metal-dependent catalytic activity toward model substrates for phosphatases (p-nitrophenyl phosphate) and phosphodiesterases (bis-p-nitrophenyl phosphate). Subsequent secondary enzymatic screens with natural substrates demonstrated significant phosphatase activity toward phosphoenolpyruvate and phosphodiesterase activity toward 2',3'-cAMP. Thus, our structural and enzymatic studies have identified the biochemical function of DR1281 as a novel phosphatase/phosphodiesterase and disclosed key conserved residues involved in metal binding and catalytic activity. PMID- 17847098 TI - Context shapes: Efficient complementary shape matching for protein-protein docking. AB - We describe an efficient method for partial complementary shape matching for use in rigid protein-protein docking. The local shape features of a protein are represented using boolean data structures called Context Shapes. The relative orientations of the receptor and ligand surfaces are searched using precalculated lookup tables. Energetic quantities are derived from shape complementarity and buried surface area computations, using efficient boolean operations. Preliminary results indicate that our context shapes approach outperforms state-of-the-art geometric shape-based rigid-docking algorithms. PMID- 17847099 TI - Denatured state is critical in determining the properties of model proteins designed on different folds. AB - The thermodynamics of proteins designed on three common folds (SH3, chymotrypsin inhibitor 2 [CI2], and protein G) is studied with a simplified C(alpha) model and compared with the thermodynamics of proteins designed on random-generated folds. The model allows to design sequences to fold within a dRMSD ranging from 1.2 to 4.2 A from the crystallographic native conformation and to study properties that are hard to be measured experimentally. It is found that the denatured state of all of them is not random but is, to different extents, partially structured. The degree of structure is more abundant for SH3 and protein G, giving rise to a weaker stability but a more efficient folding kinetics than CI2 and, even more, than the random-generated folds. Consequently, the features of the unfolded state seem to be as important in the determination of the thermodynamic properties of these proteins as the features of the native state. PMID- 17847101 TI - HingeProt: automated prediction of hinges in protein structures. AB - Proteins are highly flexible molecules. Prediction of molecular flexibility aids in the comprehension and prediction of protein function and in providing details of functional mechanisms. The ability to predict the locations, directions, and extent of molecular movements can assist in fitting atomic resolution structures to low-resolution EM density maps and in predicting the complex structures of interacting molecules (docking). There are several types of molecular movements. In this work, we focus on the prediction of hinge movements. Given a single protein structure, the method automatically divides it into the rigid parts and the hinge regions connecting them. The method employs the Elastic Network Model, which is very efficient and was validated against a large data set of proteins. The output can be used in applications such as flexible protein-protein and protein-ligand docking, flexible docking of protein structures into cryo-EM maps, and refinement of low-resolution EM structures. The web server of HingeProt provides convenient visualization of the results and is available with two mirror sites at http://www.prc.boun.edu.tr/appserv/prc/HingeProt3 and http://bioinfo3d.cs.tau.ac.il/HingeProt/. PMID- 17847102 TI - Rapid acid digestion and simple microplate method for milk iodine determination. AB - Iodine deficiency leads to deficiency of thyroid hormones, which causes mental retardation in infant. Laboratory confirmation is important in its diagnosis. The major problems associated with the existing methods for iodine determination in milk samples are: 1) nonsafe alkaline solution; 2) harsh thermal condition; and 3) extra time required to complete various steps. In this study, a simple and rapid colorimetric method was investigated, which used acid digestion in combination with a rapid microplate reading format method to determine the total iodine content in milk. Sample digestion was done on 50 microL milk in metavanadate/perchloric, at 230 degrees C for 10 min. After digestion, iodine determination was based on the Sandell-Kolthoff reaction. The reaction results were read in 96-well microplates by an enzyme-linked immunosorbent assay (ELISA) reader. The determination range of the assay was between 2 and 40 microg/dL. The within-run coefficient of variation percent in three levels (3, 12, and 36 microg/dL) ranged from 6.7 to 9.3 and between-run coefficients of variation ranged from 8.6 to 12.3%. The results obtained (n=70) by the optimized method have good correlation with the results of alkaline incineration as a reference method (n=70; r2=0.907; y=0.952x+1.77). Recovery tests for accuracy assessment in six levels from 6.2 to 34.2 microg/dL) were between 91.3 and 113%. This method has enabled us to achieve 0.12 microg/dL sensitivity. The results of this study show that a quick acid digestion combined with mild thermal and low sample volume with a quick reading of assay results were the main advantages of the acid digestion and microplate reading format. PMID- 17847103 TI - Influence of sample matrix and storage on BNP measurement on the Bayer Advia Centaur. AB - The assessment and management of congestive heart failure relies increasingly on the measurement of B-type natriuretic peptide (BNP). However, the effective contribution of this biochemical test in the clinical decision making is influenced by reliability of the measure, which also depends on several preanalytical issues. Since there is controversy on the influence of the matrix and the storage conditions on BNP measurement, we compared results of BNP in serum, K2 ethylene diamine tetra-acetic acid (EDTA) plasma and lithium heparin plasma fresh samples and in matching samples stored at -20 and -80 degrees C for 1 week. BNP measured on the Bayer Advia Centaur was systematically underestimated in heparin plasma (-47%) and serum (-62%) when compared to K2 EDTA plasma. According to the established 100 ng/L cutoff value, 25% and 37% of the fresh samples collected in heparin plasma or serum were misclassified from the reference K2 EDTA fresh specimen, respectively. When compared to the fresh specimens, the mean and interindividual bias observed for samples stored at either -20 degrees C or -80 degrees C was, overall, modest for K2 EDTA plasma ( 2%) and heparin plasma (+6% and -4%, respectively), though it appeared clinically meaningful in serum (+47% and +28%, respectively). Although we can not rule out that other BNP assays using different antibodies may be not affected from degradation during storage to the same extent, results of our investigation demonstrate that K2 EDTA plasma is the most suitable specimens for BNP testing on fresh and frozen samples stored at either -20 degrees C or -80 degrees C for up to 1 week. PMID- 17847104 TI - NA1/NA2 heterozygote of Fcgr3b is a risk factor for progression of IgA nephropathy in Chinese. AB - Several studies have identified FcgRIIIb (Fcgr3b) polymorphisms that determine susceptibility to autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. The objective of the study was to clarify whether Fcgr3b allele polymorphism influence susceptibility to immunoglobulin A nephropathy (IgAN), clinical features or severity in patients with IgAN. Deoxyribonucleic acid (DNA) fragments were amplified by polymerase chain reaction (PCR) using genomic DNA from 172 unrelated, healthy blood donors and 128 IgAN patients in our Kidney Disease Centre. The present findings showed that Fcgr3b genotype influenced the disease susceptibility and severity of IgAN, although Fcgr3b polymorphism did not affect the age of the disease onset. We found that the genotype frequency of Fcgr3b heterozygote NA1/NA2 in IgAN patients in Chinese significantly higher than that of healthy donors. Furthermore, higher genotype frequency of NA1/NA2 was found also in IgAN patients with glomerulosclerosis or crescent formation than those without it. NA1/NA2 heterozygote of Fcgr3b is a risk factor for progression of IgA nephropathy in Chinese. PMID- 17847105 TI - Development of an ELISA method for detecting immune complexes between tissue nonspecific alkaline phosphatase and immunoglobulin G. AB - A convenient method for measuring immune complexes between tissue-nonspecific alkaline phosphatase (TNSALP) and immunoglobulin G (IgG) (i.e., TNSALP-IgG) would be highly useful for routine analyses. Here, we identified a surface-active agent that would dissolve membrane but not dissociate TNSALP-IgG complexes. Next, we developed an enzyme-linked immunosorbent assay (ELISA) method for detecting TNSALP-IgG complexes with two monoclonal antibodies (MoAbs): 3-29-3R was coated on assay plates and captured TNSALP-IgG from a specimen; an horseradish peroxidase (HRP)-conjugated anti-human IgG1 then reacted with captured TNSALP-IgG to form an "immunocomplex sandwich." The immunocomplex was detected via the absorbance of an HRP substrate, resulting in a semiquantitative assay. The mean absorbance of 0.195 (n=5) measured in sera from healthy donors was designated as an arbitrary unit (AU/mL) of TNSALP-IgG concentration. The ELISA values of patient sera known to contain TNSALP-IgG complexes were greater than those of normal sera (normal, 1.86 plusmn; 0.61; patient, 9.30 plusmn; 5.44), and these data were confirmed by electrophoresis. Thus, the ELISA could detect TNSALP-IgG complexes. The intraassay coefficient of variation (CV) was within 7.4% and analytical recovery was excellent. There was no significant interference from hemolytic, lipemic, or icteric serum. In summary, an ELISA using 3-29-3R MoAb and HRP-conjugated anti-human IgG1 constitutes a reliable and convenient method for the semiquantitative detection of TNSALP-IgG complexes in human serum. PMID- 17847106 TI - Collection tubes with or without gel separator did not interfere with detection of rubella virus antibodies IgM and IgG. AB - Rubella infection is an exanthematic disease, with high prevalence in the adult population. The only modality of disease that causes serious consequences is congenital rubella syndrome (CRS), which happens when a pregnant woman seronegative to rubella virus acquires the infection during early pregnancy. Due to the lack of signals and characteristic symptoms of disease, diagnosis of rubella is based essentially on laboratory tests: antibodies detection and/or virus isolation. Results of serologic tests should always be interpreted with caution, because they can be affected by the quality of blood samples, processing and storage of sera, the equipment and reagents used to perform tests, and finally by the technical expertise and training of biologists. The collection tubes with gel seem to facilitate serum separation, but on the other hand gels can retain and consequently decrease antibody titers. Therefore, we decided to investigate whether the use of collection tubes containing gel separator might interfere with rubella virus antibody detection in blood samples from children. We did not observe statistically significant differences with respect to rubella virus antibody detection (immunoglobulin M [IgM] and immunoglobulin G [IgG]) for samples collected in tubes with or without gel separator, from the two evaluated manufacturers. PMID- 17847107 TI - Evaluation of a rapid and convenient method for determination of cytomegalovirus immunoglobulin M. AB - We evaluated a method for determination of human cytomegalovirus (hCMV) immunoglobulin M (IgM) by CLIA, and analyzed its clinical value in patients with infectious mononucleosis. Serum samples from 407 participants were measured on an automatic CLIA analyzer. At the same time the serum samples were measured by enzyme-linked immunosorbent assay (ELISA). An assessment of technological quality (methodology) in diagnostic tests demonstrated that the sensitivity of CLIA was 1.0 AU/mL and the functional sensitivity was <1.6 AU/mL. The within- and between assay imprecision values for different concentrations were all under 5%. Recoveries for both methods were 96-110%. The linear regression equation between expected values and measured values was y=0.644+0.986x, and correlation coefficient was 0.9991 (P<0.0001). The receiver operating characteristic (ROC) curve showed that both the sensitivity and specificity of CLIA surpassed 90%. The area under the curve (AUC) was 0.990, which was significantly higher than that of ELISA (P<0.05). The results indicate that CLIA is an excellent method for hCMV IgM measurement, and thus may be useful for clinical diagnoses. PMID- 17847108 TI - Comparison of ATP production in whole blood and lymphocyte proliferation in response to phytohemagglutinin. AB - Lymphocyte proliferation in response to mitogens, phytohemagglutinin (PHA), concanavalin A, pokeweed, and/or specific antigens has been the method of choice for in vitro diagnosis of cell-mediated immune dysfunction. Recently, an assay to measure intracellular adenosine triphosphate (ATP) production in response to PHA has been developed that requires a shorter, overnight incubation. We compared a standard 5- to 7-day lymphocyte mitogen stimulation assay utilizing tritiated thymidine (3H-thy) incorporation to one in which ATP production in response to PHA by CD4-positive cells is measured in a luminometer that requires only 18-24 hr. A total of 20 patient samples suspected of having decreased cell-mediated immunity submitted for mitogen induced lymphocyte proliferation and 21 normal controls were tested in both assays. A comparison of these two methods has demonstrated that the screening ATP assay has a sensitivity at 24 hr of 100% in detecting decreased PHA induced lymphocyte proliferation at 5 days and a specificity of 85% in the samples obtained from normal controls. The data indicate that the ATP assay may be a useful screening tool for more rapid detection of blood samples with decreased cell-mediated immune responses. However, a positive screen should always be confirmed by 3H-thy uptake using mitogens and recall antigens like candida and tetanus. PMID- 17847109 TI - Chagas' disease: IgG isotypes against cytoplasmic (CRA) and flagellar (FRA) recombinant repetitive antigens of Trypanosoma cruzi in chronic Chagasic patients. AB - The wide range of clinical Chagas' disease manifestations, of which heart involvement is the most significant, because of its characteristics, frequency and consequences, and lack of treatment and cure, justify research in this area. Specific immunoglobulin G (IgG) antibody subclasses have been associated with human Chagas' disease. Thus, in this study, the profile of IgG subclasses against cytoplasmic (CRA) and flagellar (FRA) recombinant repetitive T. cruzi-specific antigens was correlated with cardiac (CARD, n=33), cardiodigestive (CD, n=7), and indeterminate (IND, n=20) forms of Chagas' disease by indirect enzyme-linked immunosorbent assay (ELISA). IgG subclasses were detected in almost all Chagas patients studied. Nevertheless, only specific IgG2 isotype FRA was found with a significant statistical difference in CARD patients when compared to IND patients. This result suggests the potential use of this isotype for prognostic purposes, for monitoring the progression of chronic Chagas' disease, and for predicting the risk of CARD damage. This is important information, as it could help physicians to evaluate and manage the treatment of their patients. However, a follow-up study is necessary to confirm our result. PMID- 17847111 TI - Determination of leukocyte counts in cerebrospinal fluid with a disposable plastic hemocytometer. AB - Manual microscopic cell counting in a Fuchs-Rosenthal (FR) chamber has been the gold standard for quantification of leukocytes in cerebrospinal fluid (CSF). However, for accurate determination of the number and differentiation of cells by chamber counting, hemocytometers must be prepared carefully and kept clean. Improper fitting of the chamber and coverslip changes the volume of sample introduced into the chamber well. Moreover, because conventional hemocytometers are used repeatedly and are breakable, there is a risk of exposure to potentially infectious material. To address these issues, disposable plastic hemocytometers have been developed. However, the accuracy, precision, and clinical usefulness of disposable chambers for CSF cells counting have not been determined. In the present study, we evaluated use of a disposable plastic counting chamber (C-Chip DHC-F01) by comparing its performance with that of an FR chamber for counting of CSF specimens and cell suspensions. Within-run precision of C-Chip counting was comparable or superior to that of FR chamber counting, and excellent correlation between cell counts obtained with the C-Chip chamber and FR chamber was observed. However, C-Chip chambers that were kept at 4 degrees C yielded significantly low cell counts. The disposable hemocytometer will reduce the risk of exposure to potentially infectious material. However, use of C-Chip chambers should be avoided in cold environments. PMID- 17847110 TI - Caspase-cleaved cytokeratin 18 and 20 S proteasome in liver degeneration. AB - Apoptosis of epithelial hepatocytes plays a pivotal role in acute as well as in chronic liver diseases. The cleavage of cytokeratin-18 (CK-18) by caspases is an early event in the apoptotic process. We therefore sought to investigate serum levels of CK-18 and 20S proteasome in patients with liver cirrhosis, primary graft dysfunction (PDF), and acute liver failure (ALF), and in healthy volunteers. Enzyme-linked immunosorbent assay (ELISA) was utilized to measure the concentration of M30, a fragment of CK-18 cleaved at Asp396 (M30 neoantigen), and the concentration of 20S proteasome. Serum levels of the CK-18 neoepitope M30 were significantly increased in ALF, primary graft dysfunction, and liver cirrhosis vs. healthy controls (1,993.6+/-124.7 U/L, 2,238.1+/-235.9 U/L, and 673.6+/-86.5 U/L vs. 66.8+/-29.1 U/L, respectively, P<0.001). Similar results were detected with the evaluation of 20S proteasome (124,014.5+/-13,235.6 ng/mL, 76,993.2+/-15,720.1 ng/mL, and 2,395.9+/-1,098.2 ng/mL vs. 1,074.5+/-259.4 ng/mL, respectively; P<0.001). Detection of CK-18 neoepitope M30 and 20S proteasome may represent a novel marker of tracing apoptotic epithelium, respectively mirroring degenerative liver processes in affected patient population. PMID- 17847112 TI - Levels of serum sialic acid and thiobarbituric acid reactive substances in subjects with impaired glucose tolerance and type 2 diabetes mellitus. AB - Cardiovascular disease is a common cause of death for diabetic patients. High sialic acid levels (SA) and increased oxidative stress are important factors for cardiovascular diseases. We aimed to research whether SA and thiobarbituric acid reactive substances (TBARS) levels are associated with the degree of the diabetic regulation and investigate if SA and TBARS levels can be controlled with the regulation of the blood glucose levels. A total of 179 subjects were included in the study. Three groups, which were comprised of subjects with type 2 diabetes mellitus (DM) (DM group [DMG], n=149), impaired glucose tolerance (IGT) (IGT group [IGTG], n=15), and normal oral glucose tolerance (NGT) (NGTgroup [NGTG], n=15) were constituted. Glucose, cholesterol, high-density lipoprotein (HDL) and glycated hemoglobin (HbA1C), SA, and TBARS were measured in the sera of the patients. SA and TBARS levels were significantly increased in subjects with type 2 DM (P<0.001 for both). SA concentrations showed significant correlation with triglycerides (r=0.229; P<0.05), fasting glucose (r=0.508; P<0.01), 2-hr postprandial glucose (r=0.455; P<0.01), and HbA1C (r=0.467; P<0.01), and there was a positive correlation between TBARS and HbA1C (r=0.251; P<0.01). Diabetic patients were found to have higher risk for inflammation and oxidative stress. The regulation of blood glucose levels may contribute to the decline of both SA and TBARS levels. PMID- 17847113 TI - Effect of infliximab on the glycosylation of IgG of patients with rheumatoid arthritis. AB - In patients with rheumatoid arthritis (RA) a decrease in the terminal galactose content of N-linked glycans of the Fc region of agalactosyl immunoglobulin G (IgG) (G0) occurs. The aim of this study was to evaluate, for the first time, the effect of infliximab, a new monoclonal antibody for the treatment of RA, on this phenomenon. A total of 19 patients with active RA were treated with intravenous infliximab (3 mg/kg) in combination with methotrexate (MTX) (10-20 mg). IgG was purified from their serum by caprylic acid. Analysis of IgG glycosylation was performed by lectin blotting/immunoblotting and enzyme linked lectin assay (ELLA)/enzyme linked immunosorbent assay (ELISA) using the Griffonia (bandeiraea) simplicifolia lectin II and protein-A/alkaline phosphatase. The purity of IgG samples obtained was higher than 90%. The sensitivity of the lectin/immunoblotting method was of about 0.25 microg of IgG. The inter- and intraassay coefficients of variation (CV) were 1.3% and 9.0% for lectin blotting, and 4.6% and 8.3% for immunoblotting, respectively. The sensitivity of the ELLA/ELISA approach was 0.025 microg/microL and the inter- and intraassay CV were 6.2% and 7.7% for ELLA, and 5.1% and 14.1% for ELISA, respectively. A good linear correlation (r2=0.18, P<0.05) was obtained between the two different experimental approaches. A decrease of G0 was observed in patients who clinically improved (according to the American College of Rheumatology criteria) following the pharmacological treatment. Our data indicate that infliximab can reduce the concentration of G0 in patients with active RA. PMID- 17847114 TI - IgM, IgG, and IgA rheumatoid factors in pigeon hypersensitivity pneumonitis. AB - The association of rheumatoid factor (RF) and lung disease in several immunologically mediated conditions has suggested that it may be physiopathologically relevant. Since previous reports in hypersensitivity pneumonitis (HP) have dealt mainly with the immunoglobulin M (IgM) RF measurement, we studied such antibody activity in other immunoglobulins, to determine the IgG and IgA RF levels in pigeon-HP, and in asymptomatic breeders (AB) and rheumatoid arthritis (RA) as controls. RFs were measured in 35 HP patients, 41 AB, 31 RA controls, and 55 healthy donors by enzyme-linked immunosorbent assay (ELISA) using human or rabbit immunoglobulin G (IgG), anti IgM, F(ab')2 of IgG, and IgA F(ab')2 conjugates. An affinity chromatography, fragment crystallizable (Fc) preparations of IgG, pepsin digestion, and Western blots were used to confirm RF specificity. We also evaluated anti-avian antibodies (AA) and cross-reacting antibodies. The HP group revealed positive IgM (51.4%), IgG (31.4%), and immunoglobulin A (IgA) (34.2%) RF tests, and these antibody values exceeded the AB reference levels (P<0.02). HP and RA showed a similar frequency and distribution of RFs. Possible immunoassay interferences were excluded. As in other immunologically mediated diseases, IgG and IgA RFs may play a pathogenic role in HP, amplifying the inflammatory reaction, immune complex formation, and complement activation. IgM-RF producing cells that have been implicated in the presentation of self and foreign antigens, and T-cell activation might induce the isotype switching of RFs. PMID- 17847115 TI - Insulin-like growth factor I (IGF-I) as a sensitive biomarker of catabolism in patients with gastrointestinal diseases. AB - Gastrointestinal ailments evoke changes in the hypothalamic-pituitary-adrenal (HPA) axis and modulation of hepatic protein synthesis. We examined the catabolic effect of certain primary gastrointestinal diseases and surgery on the concentration of insulin-like growth factor I (IGF-I). Blood samples from patients with gastric cancer (GC), cholecystitis (CC), or inguinal hernia (IH) were taken before and after surgery. The concentrations of IGF-I, IGF binding protein-1 (IGFBP-1), insulin, cortisol, and glucose were determined. In GC patients the concentration of IGF-I was reduced and the concentrations of IGFBP-1 and cortisol were elevated preoperatively; after surgery, IGFBP-1 normalized. In CC patients the concentration of IGF-I was low and the concentration of IGFBP-1 was high before cholecystectomy; after surgery IGFBP-1 returned to normal and the concentration of cortisol increased. In IH patients the concentration of IGF-I was low and the concentrations of IGFBP-1 and cortisol were high before surgery; after laparotomy IGFBP-1 returned to normal. The metabolic changes were present in all analyzed patient groups, regardless of the severity of disease and nutrition. The concentration of IGF-I was reduced before surgery and remained reduced after, recommending IGF-I as a metabolic marker in both pre and postoperative examination of patients. PMID- 17847116 TI - Transcription-mediated amplification linked to line probe assay as a routine tool for HCV typing in clinical laboratories. AB - Typing of hepatitis C virus (HCV) isolates is currently a prerequisite for adequate tailoring of antiviral combination therapy. In many diagnostic laboratories, there seems to be a tendency toward convenient and time-saving procedures utilizing amplification products, which are already available from preceding qualitative or quantitative HCV ribonucleic acid (RNA) assays. In this context, we evaluated the performance characteristics of a combination of techniques, i.e., transcription-mediated amplification-line probe assay (TMA LiPA), which links highly sensitive TMA of HCV RNA to the VERSANT HCV Genotype Assay (version 1). A total of 100 clinical samples were genotyped by TMA-LiPA. The obtained results were compared to those recorded by the original, nested reverse transcription (RT)-polymerase chain reaction (PCR)-based VERSANT assay, the core-related GEN-ETI-K DEIA, and phylogenetic analyses of partial sequences from the HCV core and NS5B regions. TMA-LiPA assigned the correct genotype to all 100 HCV isolates. For subtyping of genotype 1 and 2 isolates, TMA-LiPA only showed discriminatory powers of 82% and 53%, respectively. Thus, TMA-LiPA in our hands turned out as a convenient and time-saving routine procedure for HCV typing which currently provides sufficient information for clinical purposes. Like all 5'untranslated region (UTR)-based assays, the technique is limited, however, in its potentials to resolve the complexity of existing HCV subtypes. PMID- 17847117 TI - Rapid activation of ERK by 6-hydroxydopamine promotes survival of dopaminergic cells. AB - Isoforms of the mitogen-activated protein kinase ERK have been implicated in both cell survival and cell death. In the present study we explored their role in cell viability in response to oxidative stress. Using the dopaminergic MN9D cell line, we determined that cell death occurred in a concentration-dependent manner after exposure to 6-hydroxydopamine (6-OHDA). The toxicity of 6-OHDA was mediated through generation of reactive oxygen species and was accompanied by a large increase in phosphorylated ERK1/2 but no significant increase in phosphorylated ERK5. 6-OHDA produced a distinct temporal pattern of ERK1/2 activation, with phosphorylated ERK1/2 peaks occurring after 10-15 min (25-fold increase) and 6-24 hr (13-fold increase). Inhibition of the early phosphorylated ERK1/2 peak with U0126 increased the generation of reactive oxygen species by 6-OHDA as well as 6 OHDA-induced toxicity, whereas inhibition of the late peak did not affect 6-OHDA induced cell death. The time course of phosphorylation of the prosurvival protein CREB mimicked the temporal profile of ERK1/2 activation after 6-OHDA, and blocking the early phospho-ERK1/2 peak also abolished CREB activation. In contrast, activation of caspase-3 by 6-OHDA was delayed, occurring after about 6 hr, and this activation was increased by inhibition of the first phosphorylated ERK1/2 peak. These results suggest that the rapid activation of ERK1/2 in dopaminergic cells by oxidative stress serves as a self-protective response, reducing the content of reactive oxygen species and caspase-3 activity and increasing downstream ERK1/2 substrates. PMID- 17847118 TI - The glutamate-glutamine cycle is not stoichiometric: fates of glutamate in brain. AB - Although glutamate is usually thought of as the major excitatory neurotransmitter in brain, it is important to note that glutamate has many other fates in brain, including oxidation for energy, incorporation into proteins, and formation of glutamine, gamma-aminobutyric acid (GABA), and glutathione. The compartmentation of glutamate in brain cells is complex and modulated by the presence and concentration of glutamate per se as well as by other metabolites. Both astrocytes and neurons distinguish between exogenous glutamate and glutamate formed endogenously from glutamine via glutaminase. There is evidence of multiple subcellular compartments of glutamate within both neurons and astrocytes, and the carbon skeleton of glutamate can be derived from other amino acids and many energy substrates including glucose, lactate, and 3-hydroxybutyrate. Both astrocytes and neurons utilize glutamate, albeit for cell-specific metabolic fates. Glutamate is readily formed in neurons from glutamine synthesized in astrocytes, released into the extracellular space, and taken up by neurons. However, the glutamate-glutamine cycle is not a stoichiometric cycle but rather an open pathway that interfaces with many other metabolic pathways to varying extents depending on cellular requirements and priorities. PMID- 17847119 TI - Pregnancy outcome of women exposed to azathioprine during pregnancy. AB - BACKGROUND: Azathioprine (AZP) interferes with nucleic acid synthesis and is teratogenic in animals. In view of the paucity of information on the use of AZP during pregnancy we investigated this subject in a prospective, controlled, multicenter study. Our objective was too determine whether exposure to AZP during pregnancy increases the risk for major malformations and to determine the effect on pregnancy outcome. METHODS: Pregnant women on AZP who contacted one of seven teratogen information services were compared to a cohort of pregnant women who contacted two of the seven teratogen information services and took nonteratogenic treatments during their pregnancy. RESULTS: Follow-up was completed on 189 women in the AZP group and compared to 230 women in the control group. The rate of major malformations did not differ between groups with six neonates in each; the AZP rate was 3.5% and the control group rate was 3.0% (p = .775; OR 1.17; CI: 0.37, 3.69). The mean birth weight and gestational age were lower in the AZP group (2,995 g vs. 3,252 g [p = .001, difference of mean: 257, 95% CI: 106.3, 408.1] and 37.8 weeks vs. 39.1 weeks [p = .001, difference of mean: 1.3, 95% CI: .5, 2.0], respectively). The AZP group had more cases of prematurity (21.4% vs. 5.2% [p < .001; OR 4.0; 95% CI: 2.0, 8.06]) and low birth weight (23% vs. 6.0% [p < .001; OR 3.81; 95% CI: 2.0, 7.2]). CONCLUSIONS: These results suggest that AZP (50-100 mg/day) does not triple the rate of birth defects; however, it is associated with lower birth weight, gestational age, and prematurity. Larger studies are needed to confirm these observations. PMID- 17847120 TI - Nutrient intakes in women and risks of anophthalmia and microphthalmia in their offspring. AB - BACKGROUND: There is a paucity of information about risk factors for the human eye anomalies anophthalmia and microphthalmia. In this population-based case control study we investigated whether periconceptional intakes of supplemental folic acid, dietary folate, vitamin A, and several other nutrients were associated with these eye defects. METHODS: This study included data on deliveries that had estimated due dates from 1997-2002 and were part of the National Birth Defects Prevention Study (the National Birth Defects Prevention Study is a population-based case-control study of a wide spectrum of birth defects, incorporating data from 10 birth defects surveillance systems in the United States [Arkansas, California, Georgia/Centers for Disease Control and Prevention, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas, and Utah]). Cases were those infants or fetuses born with either anophthalmia or microphthalmia. Liveborn infants without major malformations were eligible as controls. Maternal interviews were conducted, primarily by telephone, in English or Spanish. Participation in the interview was 71% among case mothers and 68% among control mothers. Interviews were completed with 89 case mothers and 4,143 control mothers. A shortened version of the food frequency questionnaire from the Nurse's Health Study was used to assess frequency of intake of 58 food items during the year before pregnancy. RESULTS: Our results did not indicate reduced risks for these eye malformations associated with maternal intake of vitamin supplements containing folic acid. The data did not show an association between malformation risk and higher or lower intakes of vitamin A. We also did not observe strong evidence that an abundance or a lack of dietary intake of any other nutrient was associated with increased risk of the studied eye malformations. CONCLUSIONS: Our observations contribute to a limited body of findings on these rare eye defects. PMID- 17847121 TI - Simultaneous versus sequential pharmacokinetic-pharmacodynamic population analysis using an iterative two-stage Bayesian technique. AB - A method for simultaneous pharmacokinetic-pharmacodynamic (PK-PD) population analysis using an Iterative Two-Stage Bayesian (ITSB) algorithm was developed. The method was evaluated using clinical data and Monte Carlo simulations. Data from a clinical study with rocuronium in nine anesthetized patients and data generated by Monte Carlo simulation using a similar study design were analysed by sequential PK-PD analysis, PD analysis with nonparametric PK data and simultaneous PK-PD analysis. Both PK and PD data sets were 'rich' with respect to the number of measurements per individual. The accuracy and precision of the estimated population parameters were evaluated by comparing their mean error (ME) and root mean squared error (RMSE), respectively. The influence of PD model misspecification on the results was also investigated. The simultaneous PK-PD analysis resulted in slightly more precise population parameter estimates than the sequential PK-PD analysis and the nonparametric PK method. In the presence of PD model misspecification, however, simultaneous analysis resulted in poor PK parameter estimates, while sequential PK-PD analysis performed well. In conclusion, ITSB is a valuable technique for PK-PD population analysis of rich data sets. The sequential PK-PD method is better suited for the analysis of rich data than the simultaneous analysis. PMID- 17847122 TI - A pilot study on disseminating physical activity promotion among cancer survivors: a brief report. AB - There is growing evidence that physical activity (PA) can improve quality of life (QOL) and reduce fatigue in cancer survivors. Research staff or healthcare providers have delivered PA interventions to cancer populations. As a first step to dissemination of a previously tested PA intervention, seven American Cancer Society Reach to Recovery volunteers (mean age = 57.4 years) were trained to deliver the telephone-based intervention to 25 breast cancer survivors (mean age = 52.9 years, 56% Stage 2 cancer, mean of 3.3 years since diagnosis). A single group design was used. The theory-based intervention consisted of 12 weekly calls to encourage participants to adopt moderate-intensity PA. Participants' PA, QOL, mood, and fatigue were assessed at baseline, 12, and 24 weeks. Data on intervention feasibility and preliminary effects were collected. The intervention was feasible (mean of 10.7 out of 12 calls were delivered) and acceptable to the volunteers. At 12 weeks, there were significant increases in participants' PA and improvements in fatigue, QOL, and vigor. Effects were maintained at 24 weeks. This pilot study demonstrated that it was feasible for trained volunteers to deliver a telephone-based PA intervention to breast cancer survivors, and there were positive effects on survivors' PA behavior and psychological outcomes. PMID- 17847123 TI - Posttraumatic stress disorder among parents of children on cancer treatment: a longitudinal study. AB - The main aim of this study was to investigate the occurrence of cancer-related posttraumatic stress disorder (PTSD) among parents of children on cancer treatment. A longitudinal design with assessments at one week (T1), two (T2), and four (T3) months after the child's diagnosis was used. Two hundred and fourteen parents (107 mothers, 107 fathers) participated at T1-T3. The PTSD Checklist Civilian (PCL-C), a self-report screening instrument for PTSD, was answered by parents over the telephone. According to the PCL-C symptom criteria method 33%, more mothers than fathers, score as potential cases of acute stress disorder (ASD) at T1, whereas 28% as potential cases of PTSD at T2 and 22% at T3. The levels of acute- and posttraumatic stress symptoms show a linear, descending pattern, and mothers report higher levels than fathers. Half of the parents who score as potential cases of ASD a week after the child's diagnosis score as potential cases of PTSD four months later. The findings illustrate that a group of parents of children with cancer experience serious psychological distress related to their child's disease. A traumatic stress perspective on childhood cancer should be applied to paediatric oncology care and appropriate psychosocial interventions should be offered to parents when needed. PMID- 17847124 TI - Choices in cancer treatment: a qualitative study of the older women's (>70 years) perspective. AB - PURPOSE: Primary endocrine therapy (PET) is the treatment of primary, operable breast cancer with drugs, such as tamoxifen, rather than surgery. It is in widespread use in the UK with 40% of women over 70 years old being treated in this way. PET is associated with inferior rates of local control compared with the standard surgical therapies, but there is no difference in overall survival. There has been no published research regarding the attitudes of older women concerning these two alternative approaches to treatment; what may influence their treatment choice or their experience of either treatment modality. This study aimed to address these questions. METHOD: In-depth qualitative interviews were undertaken to explore the views of a group of 21 purposively selected older women (>70 years old), who had been treated by PET or surgery for breast cancer. The interviews were transcribed verbatim and analysed using Framework Analysis. RESULTS: Both surgery and PET were well tolerated and had high satisfaction ratings from most women. This was the case even for those who had complications following surgery or needed a change of management in the PET group. Older women expressed no age-specific fears for operative procedures. The women were passive information seekers and relied heavily on 'expert' advice in making their treatment choices. Neither social support or age were factors in their decision making. Their main concern was to ensure that their quality of life and independence remained unaffected. CONCLUSION: Older women have no strong preference for either treatment option but are concerned that the treatment is effective and causes minimal disruption to their quality of life and independence. This study suggests that medical consultations may need to be adapted to reflect the passive acceptance of 'expert' advice in the majority of women in this age group. PMID- 17847125 TI - Case report: clozapine given in the context of chemotherapy for lung cancer. AB - BACKGROUND: Despite the frequent use of the antipsychotic medication, clozapine, in chronic treatments of psychiatric patients, there is limited clinical evidence available to guide clinicians in the problematic situation of a chemotherapy induced blood dyscrasia. OBJECTIVE: To perform a literature review and add a case report to the available clinical evidence. METHOD: We gathered evidence through literature searches on Medline and with the assistance of a medical information specialist from Novartis who searched their internal database. We also report the case of a patient maintained on clozapine treatment despite full-dose chemotherapy (cisplatin and etoposide) for an extensive lung cancer. RESULT: The searches returned seven clinically relevant references. These references do not establish a synergistic effect of clozapine and chemotherapy on blood counts. However, it has been shown that clozapine exposure activates common apoptotic pathways shared with anticancer drugs. CONCLUSION: Although the meagre clinical evidence precludes drawing any general conclusion as to the safety of maintaining clozapine administration during chemotherapy, it does not point to an obvious worsening of the haematological outcomes. PMID- 17847126 TI - The domain structure of the EORTC QLQ-STO22 supported by Japanese validation data. AB - This paper evaluates the scale structure of the EORTC QLQ-STO22 gastric cancer module using Japanese validation data. We additionally tested two single items regarding dumping syndrome. Of 246 patients who participated in phase II clinical trials of chemotherapy to treat advanced gastric cancer, we analyzed 206 who completed the pretreatment questionnaire. The factor analysis supported the scale structure hypothesized for the initial development phase conducted by the EORTC Quality of Life Group, not the alternations made in the final psychometric testing phase. The elicited scales exhibited high internal consistency and high clinical validity. Our data suggest that there is no need to examine the dumping syndrome items. This study revealed a slightly different scale structure of the QLQ-STO22 from that obtained in the European study. Extensive discussions with the EORTC Group are needed from both cross-cultural and clinical perspectives in order to establish a consensus on the various language versions of the QLQ-STO22. PMID- 17847127 TI - Effects of water deprivation on the pharmacokinetics of theophylline and one of its metabolites, 1,3-dimethyluric acid, after intravenous and oral administration of aminophylline to rats. AB - It has been reported that the expressions of hepatic microsomal cytochrome P450 (CYP) 1A1/2, 2B1/2 and 3A1/2 were not changed in rats with water deprivation for 72 h (rat model of dehydration) compared with the controls. It has been also reported that 1,3-dimethyluric acid (1,3-DMU) was formed from theophylline via CYP1A1/2 in rats. Hence, it could be expected that the formation of 1,3-DMU could be comparable between the two groups of rats. As expected, after both intravenous and oral administration of theophylline at a dose of 5 mg/kg to the rat model of dehydration, the AUC of 1,3-DMU was comparable to the controls. After both intravenous and oral administration of theophylline to the rat model of dehydration, the Cl(r) of both theophylline and 1,3-DMU was significantly slower than the controls. This could be due to significantly smaller urinary excretions of both theophylline and 1,3-DMU since the AUC of both theophylline and 1,3-DMU were comparable between the two groups of rats. The smaller urinary excretion of both theophylline and 1,3-DMU could be due to urine flow rate-dependent timed interval renal clearance of both theophylline and 1,3-DMU in rats. PMID- 17847128 TI - Sensitive fluorescence detection of polyphosphate in polyacrylamide gels using 4',6-diamidino-2-phenylindol. AB - PAGE is commonly used to identify and resolve inorganic polyphosphates (polyP). We now report highly sensitive and specific staining methods for polyP in polyacrylamide gels based on the fluorescent dye, 4',6-diamidino-2-phenylindol (DAPI). DAPI bound to polyP in gels fluoresced yellow while DAPI bound to nucleic acids or glycosaminoglycans fluoresced blue. Inclusion of EDTA prevented staining of glycosaminoglycans by DAPI. We also identified conditions under which DAPI that was bound to polyP (but not nucleic acids or other anionic polymers) rapidly photobleached. This allowed us to develop an even more sensitive and specific negative staining method that distinguishes polyP from nucleic acids and glycosaminoglycans. The lower LOD using DAPI negative staining was 4 pmol (0.3 ng) phosphate per band, compared to conventional toluidine blue staining with a lower LOD of 250 pmol per band. PMID- 17847129 TI - A fast CE method for the achiral separation of methadone and its major metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine and 2-ethyl-5 methyl-3,3-diphenyl-1-pyrroline. AB - The utilization of dynamic doubly coated capillaries for a fast separation of methadone and its two major metabolites, 2-ethylidene-1,5-dimethyl-3,3 diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP) was investigated. The coated capillaries were prepared using a polycation of poly(diallyldimethylammonium chloride) and a polyanion of dextran sulfate. A fast achiral separation was developed using the coated capillaries with a BGE of 100 mM phosphate buffer at pH 2.6. Complete achiral separation of methadone, EDDP and EMDP was achieved, with migration times of approximately 4 min. The method offers considerable advantages with respect to BGE simplicity and analysis time compared to previously published CE methods for methadone and its related analytes. PMID- 17847130 TI - CE methods applied to the analysis of micronutrients in foods. AB - This article reviews the applications of CE that are relevant to the analysis of small molecules in foods. CE has been applied to a wide range of important areas of food analysis and is rapidly being established as an alternative technique to chromatographic methods including HPLC and GC within analytical food and research laboratories. In recent years the analysis of food by CE has become more frequent and important and as such a variety of compounds have been separated and quantified. Although many other analytes have been detected by CE, this review will highlight areas relating primarily to the rather broad chemical classes of free amino acids, carbohydrates, organic acids, vitamins and a variety of antioxidants. In addition, information relating to the analyte, sample matrix, mode of CE employed, scope of the methodology and the detection and derivatization of the small molecules are considered and discussed. PMID- 17847131 TI - CZE for the speciation of arsenic in aqueous soil extracts. AB - We developed two separation methods using CZE with UV detection for the determination of the most common inorganic and methylated arsenic species and some phenylarsenic compounds. Based on the separation method for anions using hydrodynamic sample injection the detection limits were 0.52, 0.25, 0.27, 0.12, 0.37, 0.6, 0.6, 1.2 and 1.0 mg As/L for phenylarsine oxide (PAO), p aminophenylarsonic acid (p-APAA), o-aminophenylarsonic (o-APAA), phenylarsonic acid (PAA), 4-hydroxy-3-nitrobenzenearsonic acid (roxarsone), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), arsenite or arsenious acid (As(III)) and arsenate (As(V)), respectively. These detection limits were improved by large volume sample stacking with polarity switching to 32, 28, 14, 42, 22, 27, 26 and 27 microg As/L for p-APAA, o-APAA, PAA, roxarsone, MMA, DMA, As(III) and As(V), respectively. We have applied both methods to the analysis of the arsenic species distribution in aqueous soil extracts. The identification of the arsenic species was validated by means of both standard addition and comparison with standard UV spectra. The comparison of the arsenic species concentrations in the extracts determined by CZE with the total arsenic concentrations measured by inductively coupled plasma-atomic emission spectroscopy (ICP-AES) indicated that CZE is suited for the speciation of arsenic in environmental samples with a high arsenic content. The extraction yield of phenylarsenic compounds from soil was derived from the arsenic concentrations of the aqueous soil extracts and the total arsenic content of the soil determined by ICP-AES after microwave digestion. We found that 6-32% of the total amount of arsenic in the soil was extractable by a one-step extraction with water in dependence on the type of arsenic species. PMID- 17847132 TI - CE in anticancer metallodrug research--an update. AB - With the current demographic development and the knowledge that the probability to be diagnosed with cancer increases with age, the search for new treatment options in cancer chemotherapy is of utmost importance for the society. Capillary electrophoretic methods have been applied in the last few years for studying the properties of metal-based drugs and drug candidates. Especially, the elucidation of the mode of action of such compounds could contribute significantly to design new drugs for overcoming the threat of cancer. This review article highlights the developments in metallodrug research applying CE during the last 4 years and follows a review from 2003 (Hartinger, C. G., Timerbaev, A. R., Keppler, B. K., Electrophoresis 2003, 24, 2023-2037). Most importantly the broadening of application areas of CE must be noted: especially the binding studies of metal complexes toward proteins (including the determination of association and rate constants), following redox reactions of metal complexes and their influence on the reactivity toward biotargets, etc. are important development areas of the last few years. In parallel with these new applications goes the usage of new or modified separation methods including microemulsion EKC or ACE, or the advantageous use of equipping the CE system with mass spectrometric detectors such as inductively coupled plasma (ICP) or ESI mass spectrometers (MS) for determining the degree of metallation of a protein or characterizing the adducts. Finally, upcoming requirements for expanding the method's application area are discussed including studies on new targets in the cell, analyzing real-world samples, methodological development, and contributions to improve the design of new anticancer agents. PMID- 17847133 TI - Fluorinated ethylenepropylene copolymer as a potential capillary material in CE. AB - In this work, a new generation UV-transparent polymer, fluorinated ethylenepropylene copolymer (FEP) exhibiting a low degree of crystallinity, extruded in dimensions similar to the most commonly used CE capillaries of approximately 80 mum id and about 360 mum od was investigated for its use as a CE capillary. FEP is transparent down to the low-UV region, and as fluorinated polymers in general are good electrical insulators and exhibit reasonable heat conductivity, it has considerable potential as a material for electrodriven analysis in capillary or microchip formats. The FEP capillary has been characterised with regard to some important aspects for its use as a CE capillary, including its profile of EOF versus pH, as well as procedures for manipulating EOF by coating the inner capillary wall with various semipermanent and dynamic layers. The FEP capillaries were tested and compared with fused silica capillary for the separation of inorganic and small organic ions using conditions involving direct and indirect detection in the low-UV region. Finally, advantages of the use of the FEP capillary for simultaneous detection of a mixture containing nine inorganic cations and anions using indirect photometric detection with a movable light-emitting diode (LED) detector and a novel electrolyte are demonstrated. PMID- 17847134 TI - Analysis of inorganic and small organic ions by CE with amperometric detection. AB - Capillary electrophoresis has become a widely useful analytical technology. Amperometric detection is extensively employed in capillary electrophoresis for its many inherent virtues, such as rapid response, remarkable sensitivity, and low cost of both detectors and instrumentations. Analysis of inorganic and small organic ions by capillary electrophoresis is an important research field. This review focuses on the recent developments of capillary electrophoresis coupled with amperometric detection for analysis of inorganic and small organic ions. Advancements in electrophoresis separation modes, amperometric detection modes, working electrodes, and applications of inorganic ions, amino acids, phenols, and amines are discussed. PMID- 17847135 TI - Gold nanoparticles and gold(III) complexes as general and selective hydrosilylation catalysts. PMID- 17847136 TI - ESEEM spectroscopy reveals carbonate and an N-donor protein-ligand binding to Mn2+ in the photoassembly reaction of the Mn4Ca cluster in photosystem II. PMID- 17847137 TI - Distinguishing anhydrous and hydrous forms of an active pharmaceutical ingredient in a tablet formulation using solid-state NMR spectroscopy. PMID- 17847138 TI - Highly enantioselective synthesis of alpha-hydroxy phosphonic acid derivatives by Rh-catalyzed asymmetric hydrogenation with phosphine-phosphoramidite ligands. PMID- 17847139 TI - An iron catalyst for ketone hydrogenations under mild conditions. PMID- 17847140 TI - Interrogation of single synthetic polymer chains and polysaccharides by AFM-based force spectroscopy. AB - This contribution reviews selected mechanical experiments on individual flexible macromolecules using single-molecule force spectroscopy (SMFS) based on atomic force microscopy. Focus is placed on the analysis of elasticity and conformational changes in single polymer chains upon variation of the external environment, as well as on conformational changes induced by the mechanical stress applied to individual macromolecular chains. Various experimental strategies regarding single-molecule manipulation and SMFS testing are discussed, as is theoretical analysis through single-chain elasticity models derived from statistical mechanics. Moreover, a complete record, reported to date, of the parameters obtained when applying the models to fit experimental results on synthetic polymers and polysaccharides is presented. PMID- 17847141 TI - Two-photon microscopy and spectroscopy of lanthanide bioprobes. AB - The linear and non-linear photophysical properties of tris-dipicolinate europium and terbium complexes (absorption, emission, lifetime, luminescence induced by two-photon absorption) are studied in the crystalline state as well as in protein derivative crystals and compared to those in solution. Upon laser irradiation at 532 nm, luminescence of terbium is induced by a two-photon antenna effect, whereas luminescence of europium results from one-photon absorption in forbidden f-f transitions. Finally, linear and two-photon microscopy imaging experiments on biological and bio-inspired crystals are performed. These first proof-of-concept experiments open the way for the development of time-resolved non-linear microscopy that should combine the advantages of lanthanide luminescence (long lifetime, sharp emission bands, insensitivity to oxygen) with those of confocal biphotonic excitation (near-IR excitation, 3D resolution and reduced photodamage). PMID- 17847142 TI - Assembly of hexamolybdenum metallic clusters on silicon surfaces. PMID- 17847143 TI - Synthesis, DNA-binding, cleavage, and cytotoxic activity of new 1,7-dioxa-4,10 diazacyclododecane artificial receptors containing bisguanidinoethyl or diaminoethyl double side arms. AB - Novel 1,7-dioxa-4,10-diazacyclododecane artificial receptors with two pendant aminoethyl (3) or guanidinoethyl (4) side arms have been synthesized. Spectroscopy, including fluorescence and CD spectroscopy, of the interactions of 3, 4, and their copper(II) complexes with calf thymus DNA indicated that the DNA binding affinity of these compounds follows the order Cu(2+)-4>Cu(2+)-3>4>3, and the binding constants of Cu(2+)-3 are Cu(2+)-4 are 7.2x10(4) and 8.7x10(4) M(-1), respectively. Assessment by agarose gel electrophoresis of the plasmid pUC 19 DNA cleavage activity in the presence of the receptors showed that the complexes Cu(2+)-3 and Cu(2+)-4 exhibit powerful supercoiled DNA cleavage efficiency. Kinetic data of DNA cleavage promoted by Cu(2+)-3 and Cu(2+)-4 under physiological conditions fit to a saturation kinetic profile with kmax values of 0.865 and 0.596 h(-1), respectively, which give about 10(8)-fold rate acceleration over uncatalyzed supercoiled DNA. This acceleration is due to efficient cooperative catalysis of the copper(II) center and the functional (diamino or bisguanidinium) groups. In-vitro cytotoxic activities toward murine melanoma B16 cells and human leukemia HL-60 cells were also examined: Cu(2+)-4 shows the highest activity with IC(50) values of 1.62x10(-4) and 1.19x10(-5) M, respectively. PMID- 17847144 TI - Sodium chains as core nanowires for gelation of organic solvents from a functionalized nicotinic acid and its sodium salt. AB - A new metallo-organic gelator formed from an admixture of a substituted nicotinic acid and its sodium salt is described. The nicotinic acid is substituted in the 6 position by an acetal functionality. The crystal structure of the 1:1 mixture revealed that the sodium atoms are aligned in infinite chains with the two organic units hydrogen bonded together to create potentially trinucleating ligands that encase the metal core, which leads to tube-like structures. These one-dimensional crystals were found to spontaneously gelify dichloromethane and provide pyridine gels with high thermal resistance. Gel formation was investigated by several analytical techniques, which included differential scanning calorimetry, TEM, freeze fracture electron microscopy (FFEM), IR spectroscopy and X-ray diffraction, and was found to be induced by the swelling of the one-dimensional material. FFEM and powder X-ray diffraction have revealed that the sodium chains are associated in a highly compacted state into a layered structure inside the gel. Doping these robust gels with dyes by diffusion, such as xylene cyanol, methyl yellow and bromo thymol blue, is feasible without destruction of the gels. PMID- 17847145 TI - Bis[bis-(4-alkoxyphenyl)amino] derivatives of dithienylethene, bithiophene, dithienothiophene and dithienopyrrole: palladium-catalysed synthesis and highly delocalised radical cations. AB - Five diamines with thiophene-based bridges--(E)-1,2-bis{5-[bis(4 butoxyphenyl)amino]-2-thienyl}ethylene (1), 5,5'-bis[bis(4-methoxyphenyl)amino] 2,2'-bithiophene (2), 2,6-bis[bis(4-butoxyphenyl)amino]dithieno[3,2-b:2',3' d]thiophene (3), N-(4-tert-butylphenyl)-2,6-bis[bis(4 methoxyphenyl)amino]dithieno[3,2-b:2',3'-d]pyrrole (4 a) and N-tert-butyl-2,6 bis[bis(4-methoxyphenyl)amino]dithieno[3,2-b:2',3'-d]pyrrole (4 b)--have been synthesised. The syntheses make use of the palladium(0)-catalysed coupling of brominated thiophene species with diarylamines, in some cases accelerated by microwave irradiation. The molecules all undergo facile oxidation, 4 b being the most readily oxidised at about -0.4 V versus ferrocenium/ferrocene, and solutions of the corresponding radical cations were generated by addition of tris(4 bromophenyl)aminium hexachloroantimonate to the neutral species. The near-IR spectra of the radical cations show absorptions characteristic of symmetrical delocalised species (that is, class III mixed-valence species); analysis of these absorptions in the framework of Hush theory indicates strong coupling between the two amine redox centres, stronger than that observed in species with phenylene based bridging groups of comparable length. The strong coupling can be attributed to high-lying orbitals of the thiophene-based bridging units. ESR spectroscopy indicates that the coupling constant to the amino nitrogen atoms is somewhat reduced relative to that in a stilbene-bridged analogue. The neutral species and the corresponding radical cations have been studied with the aid of density functional theory and time-dependent density functional theory. The DFT calculated ESR parameters are in good agreement with experiment, while calculated spin densities suggest increased bridge character to the oxidation in these species relative to that in comparable species with phenylene-based bridges. PMID- 17847146 TI - A new generation of metal string complexes: structure, magnetism, spectroscopy, theoretical analysis, and single molecular conductance of an unusual mixed valence linear [Ni5]8+ complex. AB - Two new linear pentanickel complexes [Ni5(bna)4(Cl)2][PF6]2 (1) and [Ni5(bna)4(Cl)2][PF6]4 (2; bna=binaphthyridylamide), were synthesized and structurally characterized. A derivative of 1, [Ni5(bna)4(NCS)2][NCS]2 (3), was also isolated for the purpose of the conductance experiments carried out in comparison with [Ni5(tpda)4(NCS)2] (4; tpda=tripyridyldiamide). The metal framework of complex 2 is a standard [Ni5]10+ core, isoelectronic with that of [Ni5(tpda)4Cl2] (5). Also as in 5, complex 2 has an antiferromagnetic ground state (J=-15.86 cm(-1)) resulting from a coupling between the terminal nickel atoms, both in high-spin sate (S=1). Complex 1 displays the first characterized linear nickel framework in which the usual sequence of NiII atoms has been reduced by two electrons. Each dinickel unit attached to the naphthyridyl moieties is assumed to undergo a one-electron reduction, whereas the central nickel formally remains NiII. DFT calculations suggest that the metal framework of the mixed-valence complex 1 should be described as intermediate between a localized picture corresponding to NiII-NiI-NiII-NiI-NiII and a fully delocalized model represented as (Ni2)3+-NiII-(Ni2)3+. Assuming the latter model, the ground state of 1 results from an antiferromagnetic coupling (J=-34.03 cm(-1)) between the two (Ni2)3+ fragments, considered each as a single magnetic centre (S=3/2). An intervalence charge-transfer band is observed in the NIR spectrum of 1 at 1186 nm, suggesting, in accordance with DFT calculations, that 1 should be assigned to Robin-Day class II of mixed-valent complexes. Scanning tunnelling microscopy (STM) methodology was used to assess the conductance of single molecules of 3 and 4. Compound 3 was found approximately 40% more conductive than 4, a result that could be assigned to the electron mobility induced by mixed-valency in the naphthyridyl fragments. PMID- 17847147 TI - Vesicles of a new salt-free cat-anionic fluoro/hydrocarbon surfactant system. AB - Weakly basic tetradecyldimethylaminoxide (C14DMAO) molecules can be protonated to form a cationic surfactant, C14DMAOH+, by an acidic fluorocarbon surfactant, an 8 2-fluorotelomer unsaturated acid (C7F15CF==CHCOOH), to form a salt-free cationic and anionic (cat-anionic) fluoro/hydrocarbon surfactant system in aqueous solution. The high Krafft point of C7F15CF==CHCOOH was largely reduced as a result of being mixed with a C14DMAO micelle solution. A study of the phase behavior of the new salt-free cat-anionic fluoro/hydrocarbon surfactant system clearly indicates the existence of a birefringent Lalpha-phase region at (25.0+/ 0.1) degrees C. The birefringent Lalpha phase consists of vesicles, which include uni- and multilamellar vesicles with one to dozens of shells, and oligovesicular vesicles, as demonstrated by freeze-fracture and cryo-transmission electron microscopy (FF- and cryo-TEM) images. The size distribution and structural transitions in the salt-free cat-anionic fluoro/hydrocarbon surfactant system were studied by dynamic light scattering (DLS) and 1H and 19F NMR spectroscopy. The formation of a salt-free cat-anionic vesicle phase could be induced by the strong electrostatic interaction between the cationic hydrocarbon C14DMAOH+ and the anionic fluorocarbon C7F15CF==CHCOO-, which provided evidence that the electrostatic interaction between the cationic and anionic surfactants is larger than the nonsynergistic interaction between the stiff fluorocarbon and the soft hydrocarbon chains of the surfactants. PMID- 17847148 TI - A convergent Pd-catalyzed asymmetric allylic alkylation of dl- and meso divinylethylene carbonate: enantioselective synthesis of (+)-australine hydrochloride and formal synthesis of isoaltholactone. AB - The use of a mixture of dl- and meso-divinylethylene carbonate as an electrophile in palladium-catalyzed asymmetric allylic alkylation reactions is reported. From the diastereomeric mixture of meso and chiral racemic starting materials, a single product is obtained in high optical purity employing either oxygen or nitrogen nucleophiles. The resulting dienes have proven to be versatile synthetic intermediates as each carbon is functionalized for further transformation and differentiated by virtue of the reaction. A mechanism for this intriguing transformation is proposed and a concise enantioselective total synthesis of (+) australine hydrochloride is reported as well as a formal synthesis of isoaltholactone. PMID- 17847149 TI - Supramolecular circular helicates formed by destabilisation of supramolecular dimers. AB - The effect of changes in the angles at the connection points of linear/circular helicates is explored as a route to control the nuclearity and architecture of metallo-supramolecular arrays. This effect is probed by changing the geometry of the metal centre used to assemble bis-pyridylimine ligands that contain a 1,3 bis(aminomethyl) benzene spacer group. Tetrahedral metal ions favour linear dimers, whereas octahedral nickel(II) predominantly gives a triangular circular helicate. Five-coordinate copper(II) falls in the middle of these extremes and results in the formation of solvent-dependent mixtures of dimer and trimer. The trinuclear, triangular, circular helicate structures, which result from coordination to copper(II) and nickel(II), are structurally characterised by X ray crystallography and reveal that the units can aggregate into hexagonal arrays that contain anion-filled tube-like channels in the solid state. PMID- 17847150 TI - Chemistry of organometallic compounds on silicon: the first step in film growth. AB - The continuous decrease in size of electronic devices has reached a critical point at which the molecular-level understanding of chemical processes is imperative. Metal-containing films, an important part of every circuit, are currently deposited from a myriad of organometallic compounds, in order to control the first stages of film growth and ultimately produce an atomically defined interface. This article outlines recent molecular-level investigations on reactions of organometallic compounds with silicon surfaces. The role of surface structure and chemical state is placed in a framework of future challenges and opportunities for applications in electronics. PMID- 17847151 TI - Electronic structures of five-coordinate complexes of iron containing zero, one, or two pi-radical ligands: a broken-symmetry density functional theoretical study. AB - The electronic structures of a series of five-coordinate complexes of iron containing zero, one, or two bidentate, organic pi-radical ligands and a monodentate ligand (pyridine, iodide) have been studied by broken-symmetry (BS) density functional theoretical (DFT) methods. By analyzing the set of corresponding orbitals[5] (CO) a convenient division of the spin-up and spin-down orbitals into 1) essentially doubly-occupied molecular orbitals (MO), 2) exactly singly-occupied MOs, 3) spin-coupled pairs, and 4) virtual orbitals can be achieved and a clear picture of the spin coupling between the ligands (non innocence vs. innocence) and the central metal ion (dN configuration) can be generated. We have identified three classes of complexes which all contain a ferric ion (d5) with an intrinsic intermediate spin (SFe= 3/2) that yield 1) an St=3/2 ground spin state if the two bidentate ligands are closed-shell species (innocent ligands); 2) if one pi-radical ligand is present, an St=1 ground state is obtained through intramolecular antiferromagnetic coupling; 3) if two such radicals are present, an St=1/2 ground state is obtained. We show unambiguously for the first time that the pentane-2,4-dione-bis(S-alkylisothiosemicarbazonato) ligand can bind as pi-radical dianion (L.TSC)2- in [FeIII(L.TSC)I] (St=1) (6); the description as [Fe IV(L TSC(3-))I] is incorrect. Similarly, the diamagnetic monoanion in 14 must be described as [FeIII(CN)2(L.TSC)](-) (St=0) with a low spin ferric ion (d5, SFe=1/2) coupled antiferromagnetically to a pi-radical ligand; [FeII(CN)2(L TSC-]- is an incorrect description. PMID- 17847152 TI - Intermediates in the destruction of chlorinated C1 hydrocarbons on La-based materials: mechanistic implications. AB - Activity experiments using GC analysis of reactor effluent have been combined with in situ IR spectroscopy to elucidate the reaction steps in the destructive adsorption of CHCl3, CH2Cl2, and CH3Cl over LaOCl. The IR results show that during reaction, LaOCl is covered with carbonate, formate, and methoxy groups. The relative amount of each of these surface intermediates depends on the Cl/H ratio of the reactant. The decomposition of the surface species leads to formation of the reaction products, and is influenced by the temperature and the relative amount of Cl present on the surface. The GC results show that the activity for the destructive adsorption of H-containing chlorinated C1 compounds decreases with increasing hydrogen content of the reactant. The acquired insight into the mechanism of destructive adsorption is crucial to the design of new catalyst materials for the efficient conversion of chlorinated hydrocarbons into nonhazardous products or reusable chemicals. PMID- 17847153 TI - Contrasting pKa of protonated bis(3-aminopropyl)-terminated polyethylene glycol "Jeffamine" and the associated thermodynamic parameters in solution and covalently attached to graphite surfaces. AB - The pKa value of protonated Jeffamine (bis(3-aminopropyl) terminated polyethylene glycol) in solution and attached as a monolayer to graphite surfaces has been determined using potentiometric titration. The protonated Jeffamine was found to have a pKa value of 9.7 in solution at 25 degrees C, whereas this value decreases to 7.1 when it is attached to a graphite surface. Potentiometric titrations from 25 to 40 degrees C allowed us to determine the surface pKa of the protonated Jeffamine at each temperature studied and hence to determine the enthalpy, entropy and Gibbs energy changes associated with the deprotonation of the amino terminated surface bound Jeffamine groups. It was found that the enthalpic contribution is negligibly small and the evaluation of these thermodynamic parameters controlling the shift in surface pKa value indicates that this process is controlled by entropic contribution arising from the ordering/disordering of solvent molecules at the carbon-water interface. This suggests that the long chain Jeffamine molecules are oriented on the carbon surface rather than existing in the bulk solution. PMID- 17847154 TI - Controllable monodisperse multiple emulsions. PMID- 17847155 TI - Transformation of nitrile to cyanide and aldehyde using a cobalt(II) complex and dioxygen. PMID- 17847156 TI - Comments on 'trying to be precise about vagueness' by Stephen Senn, Statistics in Medicine 2007; 26:1417-1430. PMID- 17847157 TI - Comments on 'age-period-cohort models for the Lexis diagram' by Carstensen B. Statistics in Medicine 2007; 26:3018-3045. PMID- 17847159 TI - [Managing suspected research misconduct]. PMID- 17847158 TI - Increasing client compliance to benefit animals. PMID- 17847160 TI - Luminaries of modern neurology: Q&A with John Walton. Interview by Brenda Patoine. PMID- 17847161 TI - Statement on Mumps Vaccine. An Advisory Committee Statement (ACS). PMID- 17847162 TI - Earthquake highlights mental-health issues in Peru. PMID- 17847163 TI - Shortage of psychiatrists a problem in Pakistan. PMID- 17847164 TI - Hepatitis B vaccination of men who have sex with men attending an urban STD clinic: impact of an ongoing vaccination program, 1998-2003. AB - OBJECTIVE: To evaluate the impact of an ongoing hepatitis B vaccination service offered in an urban sexually transmitted disease (STD) clinic. STUDY DESIGN: During the period 1998-2003, hepatitis B vaccine acceptance, series completion, and vaccine coverage rates were evaluated among men who have sex with men (MSM) and other clients attending the main STD clinic in San Diego County, California. RESULTS: Among 21,631 STD clinic attendees, 81% were eligible to start and 69% accepted hepatitis B vaccination. Among a cohort of MSM starting vaccination in 1998, 76% and 55% received 2 doses and 3 doses, respectively, after 1 year follow up and coverage then increased 1-2 percentage points annually to a final 2-dose and 3-dose coverage of 80% and 62%, respectively. Vaccine coverage (>=1 prior vaccine dose) among STD clinic attendees in 2003 was 45% compared to only 11% in 1998, the first year of the program. CONCLUSIONS: Hepatitis B vaccination can be integrated into STD clinic services with reasonable levels of vaccine acceptance and series completion. The increase in vaccination coverage over time indicates that a sustained hepatitis B immunization program can achieve acceptable vaccine coverage in high-risk populations. PMID- 17847165 TI - Human papillomavirus seroprevalence among young male and female drug users. AB - OBJECTIVES: To determine seroprevalence and correlates of exposure to HPV 16, 18, and 53 among 15- to 30-year-old drug users in Baltimore, MD. STUDY DESIGN: Young, newly initiated injection and noninjection drug users underwent a behavioral risk assessment and HPV serology testing. Sex-specific analyses were performed comparing seropositive and seronegative participants using chi2, Mann-Whitney tests, and logistic regression. RESULTS: Participants (n = 553) were 43.0% female, 40.2% African American, and median age was 24 years. HPV seroprevalence among females and males, respectively, was: HPV-16, 38.2% and 7.0%; HPV-18, 42.4% and 7.3%; and HPV-53, 27.7% and 5.1%. Correlates of HPV seropositivity among females included being African American and anal sex, and among males, having had sex with another male. CONCLUSIONS: HPV seroprevalence was high among young drug users and significantly higher among females than males, supporting previous findings. Further research is required to fully understand HPV risk factors among men and the contribution of anal transmission in women. PMID- 17847166 TI - Community center of attention. IRS, Finance poised to pounce on tax-exempt status. PMID- 17847167 TI - House OKs HHS funding bill...but 276-140 vote not enough to override a veto. PMID- 17847168 TI - NQF OKs patient surveys. More accurate assessments should come, experts say. PMID- 17847169 TI - Investors for LTACs. Regulatory concerns could be causing C-suite shifts. PMID- 17847170 TI - Accused La. doctor finds support. Rally held for Pou, despite ongoing grand jury probe. PMID- 17847171 TI - Integrated's fate. Judge will break tie on board over refinancing plans. PMID- 17847172 TI - By the numbers. 20 largest health insurers, by revenue. Based on 2006 healthcare related revenue from health, life and health statutory filings. PMID- 17847173 TI - Impact of community-acquired methicillin-resistant Staphylococcus aureus in the hospital setting. AB - The epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) is undergoing a transformation as isolates of this historically health care associated pathogen are reported with increasing frequency in otherwise healthy community-dwelling individuals. This article provides a brief review of the differences between health care-associated and community-acquired MRSA and discusses the potential impact of the changing epidemiology of MRSA on the hospital setting. PMID- 17847174 TI - Emerging issues in the management of infections caused by multidrug-resistant gram-negative bacteria. AB - Accumulating evidence indicates that treating seriously ill infected patients with active antibiotics early in the course of infection is critical to improving outcomes. The most common reason for ineffective empiric therapy is resistance to the agents used. Gram-negative bacteria are becoming increasingly resistant to many commonly used antibiotics, and some cases require older, more toxic antibiotics for adequate microbial coverage. The diversity of resistance mechanisms that underly multidrug resistance makes developing effective new antimicrobial agents very difficult, especially against problematic species such as Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. This growing problem requires a multipronged strategy that includes adherence to infection control principles, parsimonious and rational use of current antimicrobial agents, and development of new agents active against multidrug resistant pathogens. PMID- 17847175 TI - Complicated skin and soft-tissue infections: diagnostic approach and empiric treatment options. AB - Skin and soft-tissue infections are common and generally are uncomplicated at the time of initial presentation. However, these infections can worsen quickly when there are delays in presentation and treatment. Upon encountering these infections, physicians must respond quickly with an appropriate therapeutic plan and be aware of trends in microbial resistance in order to optimize patient care. PMID- 17847176 TI - Empiric treatment options in the management of complicated intra-abdominal infections. AB - Complicated intra-abdominal infections remain a major challenge for surgeons and internists because of their association with high morbidity and mortality. For optimal outcome, these infections require a combination of appropriate and timely surgical source control and adjunctive broad-spectrum antimicrobial therapy. This review discusses criteria for choosing empiric antimicrobial therapy, outlines available treatment options, and highlights new antimicrobial therapies for these infections. PMID- 17847177 TI - Antibacterial treatment strategies in hospitalized patients: what role for pharmacoeconomics? AB - Antimicrobial agents continue to account for a significant portion of institutional pharmaceutical expenditures. Pharmacoeconomic analysis is a valuable tool in assessing antibacterial agents for their place in institutional formularies. This article reviews various types of pharmacoeconomic analyses, their respective limitations, and their roles in the antibacterial formulary decision-making process. We also discuss the current state of the antibacterial pharmacoeconomic literature, including the economic impact of antimicrobial resistance. PMID- 17847178 TI - [Porto novo 2: Considerations on the integration of the environment and health in Italy]. PMID- 17847179 TI - [The international and European obligation in matters of environment and health]. PMID- 17847180 TI - [Legislative and organizational obligations of the Ministry of the Environment on the subject of integration between environment and health]. PMID- 17847181 TI - Special interest GPs. Special branch. AB - Special interest GPs can cut down on hospital referrals but there is no evidence that their role reduces hospital outpatient waiting times. There is no evidence of different clinical outcomes between GPSI and hospital clinics. Patients place the quality of their consultation and the expertise of the doctor ahead of accessibility. PMID- 17847182 TI - Special interest GPs. A world away. AB - An ageing population and increased numbers of those with long-term conditions will require more community based services. Primary care is under pressure to delvier new services but there are concerns over quality, cost and demand PMID- 17847183 TI - Partners in prevention. PMID- 17847184 TI - Benchmarking. Feedback loop. PMID- 17847186 TI - Taking religion seriously. PMID- 17847187 TI - Overseeing quality improvement. PMID- 17847185 TI - Taking religion seriously. PMID- 17847188 TI - Biological effects of chemical agents. PMID- 17847189 TI - Narcotic antagonists. PMID- 17847190 TI - Vitanmin C. PMID- 17847191 TI - Letters to the editor. PMID- 17847192 TI - Virtuous noun verbed. PMID- 17847193 TI - Letter to the editor-2. PMID- 17847195 TI - Two cooks for the same kitchen? PMID- 17847194 TI - Letters to the editor-1. PMID- 17847196 TI - Recent solar research. PMID- 17847198 TI - Public interest science. PMID- 17847197 TI - Student evaluations of teachers. PMID- 17847199 TI - Academy food committees: new criticism of industry ties. PMID- 17847200 TI - Woods hole: winterizing the marine biological laboratory. PMID- 17847201 TI - World ethics body proposed. PMID- 17847202 TI - Hexachlorophene curbed. PMID- 17847203 TI - NIH: Protesters Try Going Through Channels. PMID- 17847204 TI - Review of cancer plan under way. PMID- 17847205 TI - Population committee launched. PMID- 17847206 TI - Laser fusion: a new approach to thermonuclear power. PMID- 17847208 TI - History, philosophy, and sociology of science. PMID- 17847207 TI - Desulfurization of coal. AB - Coal combustion is the largest single source of sulfur oxide pollution. Treatment of some major representative U.S. coals with aqueous ferric solution removes 40 to 75 percent of the sulfur content through near quantitative oxidation of the pyritic sulfur contained in the coal matrix. Elemental sulfur and iron sulfate are recovered as products of the reaction. Engineering assessment indicates that the system, when fully developed, offers high potential for the economic abatement of sulfur oxide pollution. PMID- 17847209 TI - THE ACHIEVEMENTS OF PHYSICAL CHEMISTRY. PMID- 17847211 TI - THE EMBLEMATIC USE OF THE TREE IN THE DAKOTAN GROUP. PMID- 17847210 TI - SECTION C.--CHEMISTRY. PMID- 17847212 TI - CURRENT NOTES ON METEOROLOGY. PMID- 17847213 TI - CURRENT NOTES ON ANTHROPOLOGY. PMID- 17847214 TI - INORGANIC CHEMISTRY. PMID- 17847215 TI - GEOLOGY IN THE COLLEGES AND UNIVERSITIES OF THE UNITED STATES. PMID- 17847217 TI - THE DEFINITION OF CIVIL ENGINEERING. PMID- 17847216 TI - ON A SUPPOSED IMMEDIATE EFFECT OF POLLEN. PMID- 17847219 TI - Evidence of single-file diffusion in zeolites. PMID- 17847220 TI - Where It's At. PMID- 17847218 TI - Sociobiology's Successes. PMID- 17847221 TI - Meetings & Conferences. PMID- 17847222 TI - The Principle of Nuclear Induction. PMID- 17847223 TI - Research in Nuclear Magnetism. PMID- 17847225 TI - ASPECTS OF EDUCATION. PMID- 17847224 TI - Dangers for Science? or, Snares for the Scientist? PMID- 17847226 TI - THE ELECTRICAL ENGINEERING DEPARTMENT OF CORNELL. PMID- 17847228 TI - BRITISH UNIVERSITIES AND THE TRAINING OF TEACHERS. PMID- 17847227 TI - THE STUDY OF MODERN EUROPEAN LITERATURE IN AMERICA. PMID- 17847230 TI - EXPLORATION AND TRAVEL. PMID- 17847229 TI - HEALTH MATTERS. PMID- 17847231 TI - MENTAL SCIENCE. PMID- 17847232 TI - IS THE TRUMPET-CREEPER POISONOUS? PMID- 17847233 TI - Romantic Love and Personal Beauty. PMID- 17847234 TI - M.I.T. Confrontation. PMID- 17847236 TI - Underemployment of scientists and engineers. PMID- 17847235 TI - Enlightened employment tactics. PMID- 17847237 TI - Science and society: some policy changes are needed. PMID- 17847238 TI - Research, teaching, and faculty fate. PMID- 17847239 TI - Hydrogen-bond stereochemistry and "anomalous water". PMID- 17847240 TI - National research council: and how it got that way. PMID- 17847242 TI - Handler Dissents on NSF Budget. PMID- 17847243 TI - Whole body response of the moon to electromagnetic induction by the solar wind. AB - A comparison has been made of the interplanetary magnetic field as measured both by Apollo 12 on the lunar surface and by Explorer 35 in orbit around the moon. Two examples are given, one of a step change in the field vector and another of a sinusoidally varying field. A large response measured on the surface is attributed to confinement of the induced field lines between the streaming solar plasma and the high-conductivity interior. A steep bulk electrical conductivity gradient in the lunar crust is implied, with a confining layer roughly 100 kilometers deep. PMID- 17847244 TI - Surface-related mercury in lunar samples. AB - Lunar samples contain mercury, which may be volatilized at lunar daytime temperatures. Such mercury may constitute part of the tenuous lunar atmosphere. If mercury can escape from the atmosphere by a nonthermal mechanism, an interior reservoir or exterior sources (such as meteorite infall or solar wind, or both) are required to replenish it. Core samples exhibit an increase in surface-related mercury with depth, which suggests that a cold trap exists below the surface. The orientation of rocks on the lunar surface may be inferred by differences in the amounts of surface-related mercury found on exterior and interior samples. PMID- 17847245 TI - Selenium and sulfur in a greenland ice sheet: relation to fossil fuel combustion. AB - In the combustion of fossil fuels, selenium is mobilized in the atmosphere to a much lesser extent than is sulfur. This difference is ascribed to the chemical behavior of their respective tetravalent oxides. The ratio of selenium to sulfur in glacial ice is characteristic of terrestrial matter, and these elements may find their way to ice sheets by the formation of volatile compounds in biochemical processes. PMID- 17847246 TI - Hydroxyl orientation in muscovite as indicated by electrostatic energy calculations. AB - The electrostatic energy of the 2M(1) muscovite structure, KAl(2)(Si(3)Al)- O(10)(OH)(2), has been calculated as a function of the orientation of the hydroxyl group (O-H distance = 0.97 angstrom). The minimum in the electrostatic energy occurs when the OH bond makes an angle of 18 degrees with the cleavage plane and an angle of 31 degrees with the b-axis (in the a-b plane), which is 2.5 degrees away from the orientation of the transition moment as determined from infrared measurements on single crystals. If the K+ ion is excluded from the calculation, the O-H bond makes an angle of 53 degrees with the cleavage plane. This indicates the strong influence that the interlayer cation exerts on the hydroxyl hydrogen in mica structures. PMID- 17847248 TI - Lunar "anorthosite"? PMID- 17847247 TI - Polywater or sodium acetate? AB - Measurements of the infrared spectrum of sodium acetate suggest that high concentrations of this impurity may account for the unique spectrum of anomalous water. PMID- 17847249 TI - This week in science. PMID- 17847250 TI - A new approach to faculty salaries. PMID- 17847251 TI - Spy Satellites: Entering a New Era: Intelligence agencies are launching a constellation of new reconnaissance satellites with broad military and arms control implications; but can the data be handled? PMID- 17847252 TI - Culliton named to new post. PMID- 17847254 TI - EPA's Plan for Cooling the Global Greenhouse: A new report lists a dozen plausible actions that, if begun in the 1990s, could reduce global warming 60% over the next century. PMID- 17847253 TI - DOD Lists Critical Technologies. PMID- 17847255 TI - Japan Lays Out Welcome Mat for U.S. Scientists: New programs seek to entice researchers to spend time in Japanese labs, but many fellowships go begging. PMID- 17847256 TI - Check on figerprint news. PMID- 17847257 TI - Treasuring the moon for 20 years. PMID- 17847258 TI - Probing the chemistry of the brain. PMID- 17847259 TI - The outlook for the equipment industry. PMID- 17847260 TI - Star formation in irregular galaxies. AB - Irregular galaxies can be viewed as laboratories for studying the processes of star formation. This class of galaxy, unlike the more familiar spiral galaxies, forms stars without spiral arms and does so from a chemically less-evolved interstellar medium. In this article the problems associated with star formation in irregular galaxies are outlined and their relevance to our understanding of star formaton as a general astrophysical process is discussed. PMID- 17847261 TI - Radar detection of phobos. AB - Radar echoes from the martian satellite Phobos provide information about that object's surface properties at scales near the 3.5-cm observing wavelength. Phobos appears less rough than the moon at centimeter-to-decimeter scales. The uppermost few decimeters of the satellite's regolith have a mean bulk density within 20% of 2.0 g cm(-3). The radar signature of Phobos (albedo, polarization ratio, and echo spectral shape) differs from signatures measured for small, Earth approaching objects, but resembles those of large (>/=100-km), C-class, mainbelt asteroids. PMID- 17847262 TI - Directed movement of latex particles in the gynoecia of three species of flowering plants. AB - The secretory matrix of the stylar-transmitting tract of angiosperms has been characterized as a nutrient medium for the growth of pollen tubes, acting to guide tubes to the ovules. When nonliving particles (latex beads) were artificially introduced onto the transmitting tracts of styles of Hemerocallis flava, Raphanus raphanistrum, and Vicia faba, they were translocated to the ovary at rates similar to those of pollen tubes. Direct observations were made on the movement of individual beads along the secretory epidermis in the style and ovary of Vicia faba. The transmitting tract may play an active role in extending tube tips to their destination in the ovary. PMID- 17847264 TI - Response: asymmetries of clade shape and the direction of evolutionary time. PMID- 17847263 TI - Asymmetries of clade shape and the direction of evolutionary time. PMID- 17847265 TI - Gordon research conferences. PMID- 17847267 TI - Water-formed structures: geomorphology and hydrology of karst terrains. PMID- 17847266 TI - Cortical consolidation: neurobiology of neocortex. PMID- 17847268 TI - The bee situation: africanized honey bees and bee mites. PMID- 17847269 TI - Geothermometry: thermal history of sedimentary basins. PMID- 17847270 TI - Products & materials. PMID- 17847271 TI - THE OBJECT OF ASTRONOMICAL AND MATHEMATICAL RESEARCH. PMID- 17847273 TI - MATHEMATICS, ASTRONOMY AND PHYSICS AT THE CALIFORNIA MEETING. PMID- 17847272 TI - THE PLACE OF FORESTRY AMONG NATURAL SCIENCES. PMID- 17847275 TI - THE JOURNAL "ISIS". PMID- 17847274 TI - OCCURRENCE OF SILVER SCURF OF POTATOES IN THE SALT LAKE VALLEY, UTAH. PMID- 17847276 TI - A SIMPLE DEVICE FOR COUNTING SEEDS. PMID- 17847278 TI - HOW CAN WE ADVANCE THE SCIENTIFIC CHARACTER OF THE WORK DONE IN THE AMERICAN AGRICULTURAL EXPERIMENT STATIONS? PMID- 17847277 TI - FRATERNITY GRADES AT PURDUE UNIVERSITY. PMID- 17847279 TI - A DEVICE FOR PROJECTING A SMALL SPOT OF LIGHT SUITABLE FOR EXPLORING PHOTOSENSITIVE AREAS. PMID- 17847281 TI - THE AMERICAN MATHEMATICAL SOCIETY. PMID- 17847280 TI - THE AMERICAN PHYSIOLOGICAL SOCIETY. PMID- 17847282 TI - JAMES DWIGHT DANA. PMID- 17847284 TI - HELMHOLTZ. PMID- 17847283 TI - PASTEUR. PMID- 17847285 TI - CURRENT NOTES ON PHYSIOGRAPHY. PMID- 17847287 TI - CHEMISTRY. PMID- 17847286 TI - ASTRONOMY. PMID- 17847289 TI - ETHNO-BOTANIC GARDENS. PMID- 17847288 TI - THE INVERTED IMAGE ON THE RETINA. PMID- 17847290 TI - MARSH GAS UNDER ICE. PMID- 17847292 TI - M. PASTEUR AND HYDROPHOBIA. PMID- 17847291 TI - TORNADO LOSSES AND INSURANCE. PMID- 17847293 TI - SCIENCE NEWS. PMID- 17847295 TI - OBITUARY. PMID- 17847294 TI - RESEARCH TREND OF MEDICAL BACTERIOLOGY. PMID- 17847296 TI - PRATT AND AIRY AND ISOSTASY. PMID- 17847297 TI - THE DELUSIVENESS OF FILTERING COMPOUND SOUNDS. PMID- 17847298 TI - AMERICAN LINGUISTICS. PMID- 17847299 TI - A SOURCE OF STUDY MATERIAL FOR THE COUNTRY MAMMALOGIST. PMID- 17847300 TI - IRON TOXICITY FROM LIMING. PMID- 17847301 TI - AN APPARATUS FOR COUNTING SAND GRAINS. PMID- 17847302 TI - A UNIT FOR KYMOGRAPH RECORDING. PMID- 17847303 TI - CORRELATION OF THE FISH LAKE VALLEY AND CEDAR MOUNTAIN BEDS IN THE ESMERALDA FORMATION OF NEVADA. PMID- 17847304 TI - SEED TRANSMISSION OF COTTON WILT. PMID- 17847305 TI - Human beta-Endorphin Available. PMID- 17847306 TI - Liposomes: clinical potential. PMID- 17847307 TI - Information dissemination: whatever happened to the weinberg report? PMID- 17847308 TI - Organization of the climate program. PMID- 17847309 TI - Carbon-14 time scale extended: comparison of chronologies. AB - Thermal diffusion isotopic enrichment of carbon-14 has extended the radiocarbon dating range to about 75,000 years ago. Twenty-eight samples obtained up to June 1976, mainly from northwest Europe, were dated. Consideration of the basic assumptions of carbon-14 dating and of the sources of contamination indicates that the ages are generally reliable. Together with the pollen analytic and stratigraphic the dates yield a more detailed radiocarbon time scale for climatic variations in northwest Europe, showing three early glacial interstades. The radiocarbon time scale agrees with the Camp Century chronology and with the thorium-230 ages of corals representing high sea level stands on New Guinea. Ther is a discrepancy between the radiocarbon time scale and the deep-sea chronology, which may be due to correlation errors. With a modified interpretation of the correlation, all four time scales agree within the estimated experimental uncertainties of the dating techniques used. PMID- 17847310 TI - North american glacial history extended to 75,000 years ago. AB - By concentrating carbon-14 through thermal diffusion, it is possible to extend the range of carbon-14 dating to 75,000 years ago. Samples with very low contamination levels have been encountered, and a reliable chronology appears possible. A Pacific Northwest climatic curve has been derived from palynological studies. The Pacific Northwest curve and the Great Lakes glacial history are age calibrated by radiocarbon dating. The climatic patterns in the Pacific Northwest and Northwest Europe are similar in the early part of the last glaciation, with interstades near 60,000, 65,000, and 70,000 years ago. An age of 74,700 years for the St. Pierre interstade indicates a possible correlation with the previous interglacial. PMID- 17847311 TI - The skylab is falling and sunspots are behind it all. PMID- 17847312 TI - Another ford energy study: a hard look at coal. PMID- 17847313 TI - Doctors' fees--free from the law of supply and demand. PMID- 17847314 TI - An alaska lands bill to please environmentalists. PMID- 17847315 TI - Government seeking ways to encourage aquaculture. PMID- 17847316 TI - Plate tectonics: what forces drive the plates? PMID- 17847317 TI - The media: the image of the scientist is bad. PMID- 17847318 TI - Moratorium on Nomination of AAAS Fellows. PMID- 17847319 TI - Annual meeting--a potpourri. PMID- 17847320 TI - For the library. PMID- 17847321 TI - AAAS Cross Country. PMID- 17847323 TI - Zea mays. PMID- 17847322 TI - Future directions report available. PMID- 17847324 TI - Calcium ion interactions. PMID- 17847325 TI - Pathways of lipid metabolism. PMID- 17847326 TI - Settlement anthropology. PMID- 17847327 TI - New low-dimensional molecular metals: single-crystal electrical conductivity of nickel phthalocyanine iodide. AB - Single crystals of NiPcI(1.0) (Pc = phthalocyanine), which are composed of one dimensional stacks of (NiPc)(+0.33) molecules and chains of I(3)(-) molecules, exhibit metallic electrical conductivity in the stacking direction. At room temperature the mean free path of the carrier is 3.3 to 8.2 angstroms. PMID- 17847328 TI - Periodicity and chaos in coupled nonlinear oscillators. AB - A system of coupled tunnel diode relaxation oscillators shows a variety of complex periodic states as the external voltage is varied. The existence of chaotic or nonperiodic states is more dependent on the nature of the coupling than on the number of degrees of freedom. A simple but accurate numerical model shows many of the phenomena observed experimentally. PMID- 17847329 TI - Separation of the sperm agglutinin and the acrosome reaction-inducing substance in egg jelly of starfish. AB - The egg jelly of the starfish Asterias amurensis was separated into the fractions J1, J2, and J3 on a Sephadex G-100 column. The Jl fraction induced the acrosome reaction and J2 induced sperm agglutination. Chemical analysis and chromatography revealed that sperm agglutinin is similar to asterosaponin A. PMID- 17847330 TI - Tunicate eggs utilize ammonium ions for flotation. AB - Unlike most solitary ascidians, Corella willmeriana retains its eggs and embryos well past hatching. The early stages float to the top of the enlarged atrium from which they cannot escape. Ammonium ions replace other more dense substances in the cell sap of the float cells surrounding the embryo. Energy derived from glycolysis but not mitochondrial processes supports this process. PMID- 17847331 TI - Morphogenetic Responses of Cultured Totipotent Cells of Carrot (Daucus carota var. carota) at Zero Gravity. AB - An experiment designed to test whether embryos capable of developing from isolated somatic carrot cells could do so under conditions of weightlessness in space was performed aboard the unmanned Soviet biosatellite Kosmos 782 under the auspices of the joint United States-Soviet Biological Satellite Mission. Space flight and weightlessness seem to have had no adverse effects on the induction of embryoids or on the development of their organs. A portion of the crop of carrot plantlets originated in space and grown to maturity were not morphologically different from controls. PMID- 17847332 TI - Orangutan death and scavenging by pigs. AB - Pongid remains are rarely recovered from tropical rain forests. Observations of a Bornean bearded pig (Sus barbatus) scavenging an orangutan (Pongo pygmaeus) carcass and the recovery of an orangutan skull fragment corroborates evidence from Africa and suggests that the scavenging of wild pigs may play an important role in the destruction of pongid remains. PMID- 17847333 TI - Behavior and the Crustacean Molt Cycle: Changes in Aggression of Homarus americanus. AB - The phase of the molt cycle affects dominance status and the performance of agonistic acts in individual juvenile lobsters (Homarus americanus). Lobsters in the midphase of proecdysis are more aggressive than those in intermolt; the latter are more aggressive than lobsters in early or late proecdysis and those in postecdysis. PMID- 17847335 TI - A FEW STATISTICS. PMID- 17847334 TI - Migration of plutonium in rock: incorrect dispersion formula. PMID- 17847336 TI - THE THIRD COLUMBUS MEETING OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE AND ASSOCIATED SOCIETIES. PMID- 17847337 TI - GENERAL SESSIONS. PMID- 17847338 TI - ALBERT FRANCIS BLAKESLEE, PRESIDENT-ELECT. PMID- 17847339 TI - SYMPOSIA AND JOINT SESSIONS. PMID- 17847340 TI - SECRETARIES' CONFERENCE. PMID- 17847341 TI - THE ASSOCIATION PRIZE AWARD. PMID- 17847343 TI - RESOLUTIONS. PMID- 17847342 TI - SECTION ON MATHEMATICS (A) AND AFFILIATED SOCIETIES. PMID- 17847344 TI - THE ACADEMY CONFERENCE. PMID- 17847346 TI - SECTION ON PHYSICS (B) AND AFFILIATED SOCIETIES. PMID- 17847345 TI - SECTION ON CHEMISTRY (C). PMID- 17847347 TI - SECTION ON ASTRONOMY (D) AND ASSOCIATED SOCIETIES. PMID- 17847348 TI - SECTION ON GEOLOGY AND GEOGRAPHY (E) AND ASSOCIATED SOCIETIES. PMID- 17847349 TI - SECTION ON ZOOLOGICAL SCIENCES (F) AND ASSOCIATED SOCIETIES. PMID- 17847351 TI - SOCIETIES RELATED TO THE SECTION ON ZOOLOGICAL SCIENCES (F) AND THE SECTION ON BOTANICAL SCIENCES (G). PMID- 17847350 TI - SECTION ON BOTANICAL SCIENCES (G) AND AFFILIATED SOCIETIES. PMID- 17847352 TI - SECTION ON PSYCHOLOGY (I). PMID- 17847353 TI - SECTION ON ANTHROPOLOGY (H). PMID- 17847354 TI - SECTION ON MEDICAL SCIENCES (N) AND SUBSECTIONS. PMID- 17847355 TI - SECTION ON ENGINEERING (M). PMID- 17847356 TI - SECTION ON HISTORICAL AND PHILOLOGICAL SCIENCES (L) AND THE HISTORY OF SCIENCE SOCIETY. PMID- 17847357 TI - SECTION ON SOCIAL AND ECONOMIC SCIENCES (K) AND ASSOCIATED SOCIETIES. PMID- 17847358 TI - SECTION ON AGRICULTURE (O) AND ASSOCIATED SOCIETIES. PMID- 17847359 TI - VARIOUS SCIENTIFIC ORGANIZATIONS. PMID- 17847360 TI - SECTION ON EDUCATION (Q) AND AMERICAN FEDERATION OF TEACHERS. PMID- 17847361 TI - REPORT OF THE COMMITTEE ON GRANTS. PMID- 17847362 TI - THE ANNUAL SCIENCE EXHIBITION. PMID- 17847363 TI - This Week in SCIENCE. PMID- 17847364 TI - Polymers. PMID- 17847365 TI - Sciencescope. PMID- 17847366 TI - The geopolitics of nuclear waste. PMID- 17847367 TI - Bumpy road to a climate treaty. PMID- 17847369 TI - Lederman and his critics. PMID- 17847368 TI - U.s. Bites greenhouse bullet and gags. PMID- 17847370 TI - AAAS Meeting Opens With Views From the Top: Science and Real Politik. PMID- 17847371 TI - Looking for planets. PMID- 17847372 TI - Proving Einstein Right (or Wrong). PMID- 17847374 TI - World bank environment fund. PMID- 17847373 TI - Cruising the digital highway. PMID- 17847376 TI - Physicists hurting. PMID- 17847375 TI - How to win a westinghouse. PMID- 17847377 TI - Public attitudes toward gene splicing. PMID- 17847378 TI - PMA launches ad campaign. PMID- 17847379 TI - Campus drinking. PMID- 17847380 TI - Plastics Get Oriented--and Get New Properties. PMID- 17847381 TI - Transgenic crops get a test in the wild. PMID- 17847382 TI - Living polymerization methods. AB - Living polymerization techniques can be used to achieve a high degree of control over polymer chain architecture. Examples of the type of polymers that can be synthesized include block copolymers, comb-shaped polymers, multiarmed polymers, ladder polymers, and cyclic polymers. This control of structure, in turn, results in polymers with widely diverse physical properties, even though they are made from readily available low-cost monomers. PMID- 17847383 TI - Polymer-polymer phase behavior. AB - Different polymers can be combined into a single material in many ways, which can lead to a wide range of phase behaviors that directly influence the associated physical properties and ultimate applications. Four factors control polymer polymer phase behavior: choice of monomers, molecular architecture, composition, and molecular size. Current theories and experiments that deal with the equilibrium thermodynamics and non-equilibrium dynamics of polymer mixtures are described in terms of these experimentally accessible parameters. Two representative molecular architectures, binary linear homopolymer mixtures and diblock copolymers, exhibiting macrophase separation and microphase segregation, respectively, are examined in some detail. Although these model systems are fairly well understood, a myriad of mixing scenarios, with both existing and unrealized materials applications, remain unexplored at a fundamental level. PMID- 17847384 TI - Polymer brushes. AB - Polymers attached by one end to an interface at relatively high coverage stretch away from the interface to avoid overlapping, forming a polymer "brush." This simple picture may serve as the basis for models in diverse interfacial systems in polymer science, such as polymeric surfactants, stabilized suspensions of colloidal particles, and structures formed by block copolymers. The structure and dynamics of polymer brushes have been the subject of considerable theoretical and experimental activity in recent years. An account is given of recent advances in theoretical understanding of stretched polymers at interfaces, and the diverse experimental probes of systems modeled by brushes are briefly reviewed. PMID- 17847385 TI - Free energy and temperature dependence of electron transfer at the metal electrolyte interface. AB - The rate constant of the electron-transfer reaction between a gold electrode and an electroactive ferrocene group has been measured at a structurally well-defined metal-electrolyte interface at temperatures from 1 degrees to 47 degrees C and reaction free energies from -1.0 to +0.8 electron volts (eV). The ferrocene group was positioned a fixed distance from the gold surface by the self-assembly of a mixed thiol monolayer of (eta(5)C(5)H(5))Fe(eta(5)C(5)H(4))CO(2)(CH(2))(16)SH and CH(3)(CH(2))(15)SH. Rate constants from 1 per second (s(-1)) to 2 x 10(4) s(-1) in 1 molar HClO(4) are reasonably fit with a reorganization energy of 0.85 eV and a prefactor for electron tunneling of 7 x 10(4) s(-1) eV(-1). Such self-assembled monolayers can be used to systematically probe the dependence of electron transfer rates on distance, medium, and spacer structure, and to provide an empirical basis for the construction of interfacial devices such as sensors and transducers that utilize macroscopically directional electron-transfer reactions. PMID- 17847386 TI - High winds of neptune: a possible mechanism. AB - Neptune receives only 1/900th of the earth's solar energy, but has wind speeds of nearly 600 meters per second. How the near-supersonic winds can be maintained has been a puzzle. A plausible mechanism, based on principles of angular momentum and energy conservation in conjunction with deep convection, leads to a regime of uniform angular momentum at low latitudes. In this model, the rapid retrograde winds observed are a manifestation of deep convection, and the high efficiency of the planet's heat engine is intrinsic from the room allowed at low latitudes for reversible processes, the high temperatures at which heat is added to the atmosphere, and the low temperatures at which heat is extracted. PMID- 17847388 TI - AAAS Writes for Life. PMID- 17847387 TI - Nylon production: an unknown source of atmospheric nitrous oxide. AB - Nitrous oxide in the earth's atmosphere contributes to catalytic stratospheric ozone destruction and is also a greenhouse gas component. A precise budgetary accounting of N(2)O sources has remained elusive, and there is an apparent lack of source identification. One source of N(2)O is as a by-product in the manufacture of nylon, specifically in the preparation of adipic acid. Characterization of the reaction N(2)O stoichiometry and its isotopic composition with a simulated industrial adipic acid synthesis indicates that because of high rates of global adipic acid production, this N(2)O may account for approximately 10 percent of the increase observed for atmospheric N(2)O. PMID- 17847389 TI - Art that computes. PMID- 17847390 TI - Interview with fang lizhi: china, science, and human rights. PMID- 17847391 TI - Science & technology in a time of national challenge. PMID- 17847392 TI - Institutional arrangements. PMID- 17847394 TI - Products & materials. PMID- 17847393 TI - The boosting of planets. PMID- 17847396 TI - THE ROYAL SOCIETY OF CANADA. PMID- 17847395 TI - THE CALIFORNIA EARTHQUAKE. PMID- 17847397 TI - THE INTERNATIONAL METEOROLOGICAL CONFERENCE AT INNSBRUCK. PMID- 17847398 TI - Resultats du voyage du S. Y. 'Belgica' en 1897-1898-1899, sous the commandement de A. DE GERLACHE DE GOMERY; Botanique: Les Phanerogames des Terres Magellaniques; Travaux hydrographiques et instructions nautiques. PMID- 17847400 TI - THE FUTURE OF THE CRAYFISH INDUSTRY. PMID- 17847399 TI - COLLEGE ENTRANCE EXAMITNATIONS. PMID- 17847402 TI - THE SEVENTH INTERNATIONAL ZOOLOGICAL CONGRESS. PMID- 17847401 TI - TWO LETTERS OF DR. DARWIN: THE EARLY DATE OF HIS EVOLUTIONAL WRITINGS. PMID- 17847403 TI - STATISTICS OF MORTALITY. PMID- 17847405 TI - THE GENERIC CONCEPT IN THE CLASSIFICATION OF THE FLOWERING PLANTS. PMID- 17847404 TI - MINUTE OF THE FACULTY OF MEDICINE OF HARVARD UNIVERSITY ON THE RETIREMENT OF PROFESSOR BOWDITCH. PMID- 17847406 TI - INVESTIGATIONS AND COMMERCIAL TESTS IN CONNECTION WITH THE WORK OF AN ENGINEERING COLLEGE. PMID- 17847407 TI - ADDRESS BEFORE THE CENTRAL BOTANISTS. PMID- 17847408 TI - THE AMERICAN MATHEMATICAL SOCIETY. PMID- 17847409 TI - MENDELIAN INHERITANCE AND THE PURITY OF THE GAMETES. PMID- 17847410 TI - THE LOGICAL BASIS OF THE SANITARY POLICY OF MOSQUITO REDUCTION. PMID- 17847411 TI - REPORT OF THE TENTH GEOLOGICAL EXPEDITION OF HON. CHARLES H. MORRILL, SEASON OF 1905. PMID- 17847412 TI - YELLOW FEVER AND THE PANAMA CANAL. PMID- 17847414 TI - THE CONGRESS OF THE UNITED STATES. PMID- 17847413 TI - REPORT TO THE TRUSTEES OF THE ELIZABETH THOMPSON SCIENCE FUND OF PROFESSOR BOVERI'S RESEARCHES. PMID- 17847415 TI - SELECTION AND TRAINING OF STUDENTS FOR INDUSTRIAL RESEARCH. AB - To summarize, I have tried to suggest that knowledge, valuable as it is, is not considered the most important qualification for industrial research. Character, aptitude and attitudes are more important. Should they not be rated so in the college educational program? Aptitude, though it can not be trained, can and should be screened by the college more than is done to-day, to avoid the lifelong disappointments of misplacement. Character and attitudes actually are molded by college influences, for better or worse, and therefore are products of college life and are the responsibilities of the college, just as much as scholarship. The fact that the molding influence is the student body, more than the faculty, makes the problem different from that of scholarship, and a different method must be found for dealing with it. Could a method be found if sought with sufficient effort? Today we give it low priority, devoting only a small fraction of college effort to it. Why? PMID- 17847416 TI - A STIMULUS-EXPECTANCY NEED-CATHEXIS PSYCHOLOGY. PMID- 17847417 TI - DEATHS OF RUSSIAN BOTANISTS. PMID- 17847418 TI - THE WATSON SCIENTIFIC COMPUTING LABORATORY AT COLUMBIA UNIVERSITY. PMID- 17847419 TI - THE AMERICAN MUSEUM OF NATURAL HISTORY. PMID- 17847420 TI - REORGANIZATION OF THE SHEFFIELD SCIENTIFIC SCHOOL OF YALE UNIVERSITY. PMID- 17847421 TI - STAFFING SCIENCE DEPARTMENTS AFTER THE WAR. PMID- 17847422 TI - "PSYCHOLOGICAL DIFFERENCES AS AMONG RACES"? PMID- 17847423 TI - ORTHOGRAPHY OF SCIENTIFIC NAMES. PMID- 17847424 TI - REGENERATION OF ADULT MAMMALIAN SKELETAL MUSCLE IN VITRO. PMID- 17847425 TI - TRANSLITERATION OF RUSSIAN WORDS. PMID- 17847426 TI - THE BOTANICAL WORK OF THE CINCHONA MISSIONS IN SOUTH AMERICA. PMID- 17847427 TI - ORAL ADMINISTRATION OF PENICILLIN IN OIL. PMID- 17847428 TI - RIBOFLAVIN PRODUCTION BY CANDIDA SPECIES. PMID- 17847429 TI - FACTORS CONTROLLING BACTERIAL DISSOCIATION. PMID- 17847430 TI - A NEW REAGENT FOR VITAMIN A. PMID- 17847431 TI - A MODIFIED PETRI DISH FOR CONTINUOUS TEMPERATURE OBSERVATION. PMID- 17847432 TI - SOME POSSIBLE MODIFICATIONS IN THE METHODS OF PROTECTING BUILDINGS FROM LIGHTNING. PMID- 17847433 TI - THE MERCURIAL PRESSURE-GAUGE ON THE EIFFEL TOWER. PMID- 17847434 TI - SORGHUM AND SUGAR BEETS IN KANSAS. PMID- 17847435 TI - PRECIOUS AND ORNAMENTAL STONES AND DIAMOND CUTTING. PMID- 17847437 TI - THE MEAN COAST-DISTANCES OF CONTINENTS. PMID- 17847436 TI - THE PENINSULA OF KAMTCHATKA. PMID- 17847438 TI - CONSIDERATIONS CONCERNING THE FUNDAMENTS OF THEORETICAL PHYSICS. PMID- 17847439 TI - A COMPLEX VACCINE EFFECTIVE AGAINST DIFFERENT STRAINS OF INFLUENZA VIRUS. PMID- 17847440 TI - MAYNARD MAYO METCALF. PMID- 17847441 TI - THE ANNUAL REPORT OF THE FIELD MUSEUM OF NATURAL HISTORY. PMID- 17847442 TI - THE STRUCTURAL STEEL WELDING RESEARCH COMMITTEE OF THE ENGINEERING FOUNDATION. PMID- 17847443 TI - EXHIBITION OF THE WORKS OF LEONARDO DA VINCI. PMID- 17847444 TI - THE CHICAGO MEETING OF THE INSTITUTE OF FOOD TECHNOLOGISTS. PMID- 17847445 TI - RELEASE OF ACETYLCHOLINE BY SYMPATHETIC GANGLIA AND SYNAPTIC TRANSMISSION. PMID- 17847446 TI - POSTSCRIPT TO "ROGER BACON WAS MISTAKEN". PMID- 17847447 TI - A COUNTER-STATEMENT. PMID- 17847448 TI - ALCOHOL TASTE THRESHOLDS AND CONCENTRATIONS OF SOLUTION PREFERRED BY RATS. PMID- 17847449 TI - THE SYNTHESIS OF NICOTINIC ACID IN THE BODY OF SHEEP. PMID- 17847450 TI - A SPEEDIER AND LESS COSTLY METHOD OF CONCENTRATION IN NITRO-CELLULOSE IMBEDDING. PMID- 17847451 TI - BREAKDOWN OF SULFANILAMIDE MOLECULE BY ULTRA-VIOLET IRRADIATION OR CHEMICAL OXIDATION. PMID- 17847452 TI - AN INEXPENSIVE MICROPHOTOGRAPHIC CAMERA. PMID- 17847453 TI - Erratum. AB - In the Research News item on evoked potentials entitled "Testing babies for neurological problems" (17 July, p. 322), the affiliation of Ivan Bodis-Wollner was incorrectly given as Albert Einstein College of Medicine. It should have been Mount Sinai School of Medicine. PMID- 17847454 TI - Komanoff's Projections. PMID- 17847455 TI - Radiation dosimetry. PMID- 17847456 TI - Energy and chemicals from biomass. PMID- 17847457 TI - Chemical signatures for superheavy elementary particles. AB - Models of unified fundamental interactions suggest the existence of many particles in the mass range 10 x 10(9) to 100 x 10(12) electron volts. Among these may be charged particles, X(+/-), that are stable or nearly so. The X(+,)s would form superheavy hydrogen, while the X(-,)s would bind to nuclei. Chemical isolation of naturally occurring technetium, promethium, actinium, protactinium, neptunium, or americium would indicate the presence of superheavy particles in the forms RuX(-), SmX(-), (232)ThX(-), (235,236,238)UX(-), (244)PuX(-), or (247)CmX(-). Other substances worth searching for include superheavy elements with the chemical properties of boron, fluorine, manganese, beryllium, scandium, vanadium, lithium, neon, and thallium. PMID- 17847458 TI - National strategic petroleum reserve. AB - The Strategic Petroleum Reserve is intended to reduce the vulnerability of the United States to interruptions in the oil supply from foreign sources. Storage for 248 million barrels of crude oil in salt caverns and mines, with equipment for pumping and distribution, was constructed and operationally tested in a 4 year period. Its present inventory is the largest known crude oil reserve in the world. Facilities for expanding the reserve's capacity by another 290 million barrels are being developed by solution-mining in salt domes. PMID- 17847459 TI - Triage applied to british universities. PMID- 17847460 TI - AID Science Funds Emerge in New Guise. PMID- 17847461 TI - Innovation act after the fall. PMID- 17847463 TI - Small eddies proliferating in the atlantic. PMID- 17847462 TI - Louisiana puts god into biology lessons. PMID- 17847464 TI - The russians are coming? PMID- 17847465 TI - Media fellows at work reporting science. PMID- 17847466 TI - Science in its second century. PMID- 17847468 TI - Eugene, Oregon, hosts annual pacific division meeting. PMID- 17847467 TI - Fall energy seminars planned. PMID- 17847469 TI - Annual meeting washington. PMID- 17847470 TI - The endosymbiont hypothesis. PMID- 17847471 TI - A colony in greenland. PMID- 17847472 TI - Polar cap aeronomy. PMID- 17847473 TI - Primate socioecology. PMID- 17847474 TI - Organically bound metals in a solvent-refined coal: metallograms for a wyoming subbituminous coal. AB - Fractions of a solvent-refined coal that contain organically bound species of magnesium, calcium, titanium, iron, copper, or zinc have been isolated. The fractions represent a wide range of chemical types and molecular size. Their isolation is a step toward speciation. PMID- 17847475 TI - Polycrystalline echinoderm calcite and its fracture mechanics. AB - Polycrystalline calcite was revealed by scanning electron microscopy of fractured skeletal ossicles of the sea star Echinaster spinulosus (Echinodermata, Asteroidea). Whisker-like calcite crystals were observed in specimens that were loaded in stress relaxation before being fractured; rapidly broken surfaces were smooth and glassy. The crystallites were 1300 angstroms wide and at least 3600 angstroms long and were packed together in lamellae. The lamellae were wound into spirals that formed the trabecular bars. All the crystallites in an ossicle appear to be aligned in the same direction. Geometric considerations indicate that the requirement for packing the crystallites smoothly may explain the high magnesium ion concentration of echinoderm calcite. PMID- 17847476 TI - Quiet Zone Within a Seismic Gap near Western Nicaragua: Possible Location of a Future Large Earthquake. AB - A 5700-square-kilometer quiet zone occurs in the midst of the locations of more than 4000 earthquakes off the Pacific coast of Nicaragua. The region is indicated by the seismic gap technique to be a likely location for an earthquake of magnitude larger than 7. The quiet zone has existed since at least 1950; the last large earthquake originating from this area occurred in 1898 and was of magnitude 7.5. A rough estimate indicates that the magnitude of an earthquake rupturing the entire quiet zone could be as large as that of the 1898 event. It is not yet possible to forecast a time frame for the occurrence of such an earthquake in the quiet zone. PMID- 17847477 TI - Spectral analysis of tropospheric aerosol measurements obtained with a new fast response sensor. AB - A new fast response sensor was used in aircraft studies of fluctuations in the size distributions of tropospheric aerosol and their relation to fluctuations of trace gas concentrations and light scattering coefficients. Spectral analysis of data upwind of Buffalo, New York, and Houston, Texas, suggests important roles for atmospheric turbulence and chemical reaction in aerosol fluctuations. PMID- 17847479 TI - Soil-water equilibria for nonionic organic compounds. PMID- 17847478 TI - Sensitive and rapid diagnosis of potato spindle tuber viroid disease by nucleic Acid hybridization. AB - A sensitive and reliable new method for the detection of potato spindle tuber viroid in potato tubers has been developed. The method is based on hybridization of highly radioactive recombinant DNA to viroid RNA that has been attached to a solid support. The method can be automated and permits the rapid testing of large numbers of tubers. PMID- 17847480 TI - An Upper Bound to the Lightning Flash Rate in Jupiter's Atmosphere. PMID- 17847481 TI - Soil-water equilibria for nonionic organic compounds. PMID- 17847483 TI - News from interciencia. PMID- 17847482 TI - Reduced chautauqua program for 1981-82. PMID- 17847484 TI - SCIENTIFIC PERSONNEL WORK IN THE ARMY. PMID- 17847486 TI - PROFESSOR WILLIAMS AT YALE. PMID- 17847485 TI - PUMPELLY'S REMINISCENCES. PMID- 17847487 TI - ROOT PRESSURE AND ROOT EXUDATION. PMID- 17847489 TI - GENERIC LIMITATIONS. PMID- 17847488 TI - THE LILLE SOCIETY OF SCIENCES. PMID- 17847490 TI - SPECTRUM PHENOMENA DUE TO MOVING MOTES. PMID- 17847491 TI - NEGATIVE RESULTS FROM ATTEMPTED QUEEN BEE MATING IN A DOUBLE TENT INCLOSURE. PMID- 17847492 TI - FIREFLIES FLASHING IN UNISON. PMID- 17847494 TI - THE AMERICAN ANTHROPOLOGICAL ASSOCIATION. PMID- 17847493 TI - AMERICAN SOCIETY OF NAUTURALISTS. PMID- 17847495 TI - THE AMERICAN FOLK-LORE SOCIETY. PMID- 17847496 TI - SECTION-K PHYSIOLOGY AND EXPERIMENTAL MEDICINE. PMID- 17847497 TI - THE EXPERIMENTAL METHOD IN SANITARY SCIENCE AND SANITARY ADMINISTRATION. PMID- 17847498 TI - SYMPOSIUM ON YELLOW FEVER AND OTHER INSECT-BORNE DISEASES. PMID- 17847499 TI - Filariasis and Trypanosome Diseases. PMID- 17847500 TI - The Practical Results of Reed's Findings on Yellow Fever Transmission. PMID- 17847501 TI - Difficulties of Recognition and Prevention of Yellow Fever. PMID- 17847502 TI - The Practical Side of Mosquito Extermination. PMID- 17847503 TI - EYE ANOMALIES. PMID- 17847504 TI - A NEW METEORITE FROM SCOTT COUNTY, KANSAS. PMID- 17847505 TI - PRESERVING SPIDERS' WEBS. PMID- 17847506 TI - THE WALTER REED MEMORIAL FUND. PMID- 17847507 TI - RESULTS OF A REPLANTATION OF THE THIGH. PMID- 17847508 TI - SUCCESSFUL TRANSPLANTATION OF BOTH KIDNEYS FROM A DOG INTO A BITCH WITH REMOVAL OF BOTH NORMAL KIDNEYS FROM THE LATTER. PMID- 17847509 TI - NOTES ON ENTOMOLOGY. PMID- 17847510 TI - JAPANESE METEOROLOGICAL SERVICE IN KOREA AND CHINA. PMID- 17847511 TI - Population Problems and the American Eugenics Society. PMID- 17847512 TI - Meetings & Conferences. PMID- 17847513 TI - Wendell Clark Bennett: 1905-1953. PMID- 17847514 TI - Farmdale Drift. PMID- 17847515 TI - Lysenkoism in Athens. PMID- 17847516 TI - Streamflow and Flood-Frequency Studies. PMID- 17847517 TI - Bedrock Geology of the Montpelier Quadrangle, Vermont. PMID- 17847518 TI - Fabric Studies of Gravelly Sediments: An Introduction to a New Sampling Procedure. PMID- 17847519 TI - Helicopter Support for the Geologist. PMID- 17847520 TI - International Statement on I nformation Exchange Groups. PMID- 17847521 TI - Letter to the editor. PMID- 17847522 TI - Chemical and biological warfare: is propriety the issue? PMID- 17847523 TI - Letter to the editor. PMID- 17847524 TI - Chemical and biological warfare: is propriety the issue? PMID- 17847525 TI - Technological innovation. PMID- 17847526 TI - The historical roots of our ecologic crisis. PMID- 17847527 TI - One hundred periodic comets. PMID- 17847528 TI - Report from california: the governor and the university. PMID- 17847529 TI - Funnies on capitol hill. PMID- 17847530 TI - Huntsville: alabama cotton town takes off into the space age. PMID- 17847531 TI - Technological innovation: panel stresses role of small firms. PMID- 17847533 TI - Chemical and biological warfare (I): the research program. AB - The first of two articles on chemical and biological warfare (Chemical and Biological Warfare (I): The Research Program, Science, 13 January 1967) incorrectly stated that the Illinois Insti tute of Technology is among institu tions conducting research on CBW. IIT is conducting no work on CBW and does not engage in classified research. The work in question is being per formed at the Illinois Institute of Tech nology Research Institute, a separate organization affiliated administratively with IIT. PMID- 17847535 TI - Dating and authenticating works of art by measurement of natural alpha emitters. AB - A method for distinguishing between modern and old samples of lead has been used to analyze certain works of art. The basis of the method is the detection of radioactive lead-210, which decays with a 22-year half-life when it is unsupported by its long-lived precursor, radium-226. The latter is separated chemically from lead when lead and lead products are prepared from the ore. PMID- 17847536 TI - Natural displacement of pollution from the great lakes. AB - A simplified mathematical model of a lake system indicates that, if the pollution of the Great Lakes were discontinued, the natural flow through the lower Great Lakes would be sufficient to remove about 90 per cent of the waste in about 20 years. On the other hand, hundreds of years would be required to displace the pol lution from Lake Michigan and Lake Superior. PMID- 17847537 TI - Opal phytoliths in a north atlantic dust fall. AB - Minute bodies (less than 80 microns) of isotropic silica, originally precipitated by terrestrial plants, are found together with freshwater diatoms in falls of dust over the ocean. Eolian transport from Africa can explain the occurrence of similar plant remains in deep-sea sediments of the equatorial Atlantic as far west as the Mid-Atlantic Ridge. PMID- 17847538 TI - Anodic oxidation and molecular structure: influence on performance of normal saturated hydrocarbons in fuel cells. AB - Variation in the rate of anodic oxidation of normal saturated hydro carbons (at current densities of half the maximum value or higher) with the carbon number parallels the variation in the rate of diffusion (in electrochemical equivalents) of the hydrocarbon through the electrolyte. This parallelism, not previously recognized, is consistent with the concept of diffusion-influenced anode eactions. The conditions under which this behavior is expected are presented. PMID- 17847539 TI - Fossilization of an ancient (devonian) soft-bodied worm. AB - A shell-boring polychaete worm was found replaced by the min eral limonite goethite; this fossil is probably a limonite-goethite pseudo morph after pyrite, suggesting that the soft-bodied worm was originally re placed by pyrite. External structures such as a prostomium, anterior tentacle like palps, peristomial cirri, parapodia, setae bundles of the parapodia, and dorsal cirri of the parapodia are pre served. This worm resembles living members of the family Spionidae in form and habit. This discovery extends the known range of this family (Cre taceous?, Miocene to Recent) back about 365 million years to the Devo nian period. PMID- 17847541 TI - Gametophytes of four tropical fern genera reproducing independently of their sporophytes in the southern appalachians. AB - Vegetative reproduction and dispersal by way of gemmae are known to occur in four types of fern gametophytes. Although they belong to basically tropical rain forest genera, all four types have now been discovered growing natu rally in the vicinity of Highlands, North Carolina, as clones on shady, damp rocks. Their sporophytes were rare or absent. The gametophytes are now identified as Grammitis nimbata (Jenm.) Proctor, Grammitidaceae; Hymenophyllum tunbridg ense (L.) J.Sm., Hymenophyllaceae; Vittaria lineata (L.) J.Sm., Vittariaceae; and Trichomanes, probably representing several species, Hynmenophyllaceae. Identifi cation of the Grammitis was facilitated by the presence of some juvenile or dwarfed sporophytes; this constitutes the first report of this species, genus, and family for temperate North America. Growth and spread of fern gametophytes independently of, and distant from, the corresponding sporophytes is a novel phenomenon which should be investigated in other parts of the world. PMID- 17847540 TI - Plant moisture stress: evaluation by pressure bomb. AB - The recently developed technique for determining the water stress of a plant by measuring the pressure necessary to force water back to the cut surface of a severed twig is adaptable to both field and laboratory experiments. We have designed and operated an efficient portable system weighing less than 18 kilograms. Sampling variation within and among Douglas fir trees varies from less than +/- I atmosphere under low stress conditions to +/- 10 atmospheres under high stress conditions. In the measurement of plants of comparable height and similar exposure, the variation is reduced to a minimum. Values in internal water stress of Douglas fir vary from 3 to more than 40 atmospheres. Both duration and magnitude of stress are important ecologically. Pressure-bomb measurements are used to demonstrate a relation between plant distribution and internal water stress. PMID- 17847542 TI - Gordon research conferences: program for 1967. PMID- 17847543 TI - Editing a scientific encyclopedia. PMID- 17847544 TI - M. I. T.' s march 4: scientists discuss renouncing military research. PMID- 17847545 TI - Brandywine basin: defeat of an almost perfect plan. PMID- 17847547 TI - Triterpene alcohol isolation from oil shale. AB - Isoarborinol, an intact pentacyclic unsaturated alcohol, was isolated from the Messel oil shale (about 50 x 106 years old). Complex organic substances, even those very sensitive to oxidation, reduction, or acidic conditions, can thus survive without alteration for long periods. PMID- 17847546 TI - Venus clouds: test for hydrocarbons. AB - Infrared reflection spectra of hydrocarbon clouds and frosts now give a critical test of Velikovsky's prediction that Venus is surrounded by a dense envelope of hydrocarbon clouds and dusts. Venus does not exhibit an absorption feature near 2.4 microns, although such a feature is prominent in every hydrocarbon spectrum observed. PMID- 17847548 TI - Free-energy transfer in plants. AB - Free-energy transfer was used to study water transport through the soil-plant system. Resistances to free-energy transfer are proportional to resistances to water transfer. Under certain conditions, the proportionality factor is 1. For a sunflower plant in moist soil, plant resistance to free-energy transfer was 30 times the soil resistance, and root-stem-leaf resistances were in a ratio of about 2 : 1 : 1, respectively. However, root and sidered for a unit pathlength. PMID- 17847549 TI - Tidal friction and time. PMID- 17847551 TI - COMMENT AND CRITICISM. PMID- 17847550 TI - Hierarchical structures. PMID- 17847552 TI - THE AGASSIZ MUSEUM AT CAMBRIDGE. PMID- 17847553 TI - ANSWERS TO CHARGES AFFECTING THE GEOLOGICAL SURVEY. PMID- 17847554 TI - CRUISE OF THE CORWIN. PMID- 17847556 TI - ASTRONOMICAL NOTES. PMID- 17847555 TI - GEOGRAPHICAL NOTES. PMID- 17847558 TI - ST. PETERSBURG LETTER. PMID- 17847557 TI - LONDON LETTER. PMID- 17847559 TI - LETTERS TO THE EDITOR. PMID- 17847561 TI - The care of pamphlets. PMID- 17847560 TI - Flood Rock explosion. PMID- 17847562 TI - The arms of the octopus, or devil fish. PMID- 17847564 TI - THE PROBLEM OF THE INTRODUCTORY COURSE IN BOTANY. PMID- 17847563 TI - MEDICAL ZOOLOGY IN EUROPE. PMID- 17847565 TI - PRESENT STATUS OF THE AFFAIRS OF THE AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE. PMID- 17847566 TI - THE YALE FOREST SCHOOL. PMID- 17847567 TI - A QUESTION OF BIBLIOGRAPHY. PMID- 17847569 TI - WRATTEN FILTERS. PMID- 17847568 TI - THE COST OF GERMAN PUBLICATIONS. PMID- 17847570 TI - JONATHAN EDWARDS AS A FREUDIAN. PMID- 17847571 TI - LONG-TIME TEMPERATURE PREDICTION. PMID- 17847572 TI - THE AMERICAN CHEMICAL SOCIETY. PMID- 17847573 TI - Social sharing of bereavement experience by Chinese bereaved persons in Hong Kong. AB - Contrary to the belief that the Chinese do not share emotionally intense experiences, findings from a cross-sectional study of 292 respondents who lost either a spouse or a parent in the previous 2 years in Hong Kong indicated that only 10% did not share their bereavement experiences with another person. The physical health and emotional state of non-sharers was found to be no different to those who shared. In addition, the Chinese are believed to limit their social sharing of personal experiences to family members only. In our study, we found that for those who shared, the persons they shared most with were their best friends, siblings, and professionals. Non-family members are clearly eligible "sharees" for Chinese people. Differences in the reactions of sharees in good and bad sharing experiences were identified. Based on these findings, implications for bereavement care for Chinese are delineated. PMID- 17847574 TI - Imagining the alternatives to life prolonging treatments: elders' beliefs about the dying experience. AB - Deciding for or against a life-prolonging treatment represents a choice between prolonged life and death. When the death alternative is not described, individuals must supply their own assumptions. How do people imagine the experience of dying? We asked 40 elderly people open-ended questions about dying without 4 common life-prolonging treatments, eliciting beliefs about pain, length of time, loneliness, and palliative care. Beliefs were diverse, loneliness was commonly assumed, and palliation was rarely mentioned spontaneously. Results underscore needs for improved understanding of the dying process and palliative care and for fuller communication between patients and healthcare providers. PMID- 17847575 TI - Bibliography. Current world literature. Endoscopy. PMID- 17847576 TI - TRICARE; outpatient hospital prospective payment system (OPPS). Interim final rule. AB - This interim final rule implements a prospective payment system for hospital outpatient services similar to that furnished to Medicare beneficiaries, as set forth in section 1833(t) of the Social Security Act. The rule also recognizes applicable statutory requirements and changes arising from Medicare's continuing experience with this system including certain related provisions of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003. The Department is publishing this rule as an interim final rule to implement existing statutory requirements for adoption of Medicare payment methods for institutional care. Interim final rule publication will ensure the expeditious implementation of a proven hospital OPPS, providing incentives for hospitals to furnish outpatient services in an efficient and effective manner. However, public comments are invited and will be considered for possible revisions to the final rule. PMID- 17847577 TI - Revisions to the requirements applicable to blood, blood components and source plasma. Direct final rule. AB - The Food and Drug Administration (FDA) is amending the biologics regulations by removing, revising, or updating specific regulations applicable to blood, blood components and Source Plasma to be more consistent with current practices in the blood industry and to remove unnecessary or outdated requirements. We are taking this action as part of our continuing effort to reduce the burden of unnecessary regulations on industry and to revise outdated regulations without diminishing public health protection. Elsewhere in this issue of the Federal Register, we are publishing a companion proposed rule under our usual procedures for notice and comment in the event that we receive any significant adverse comments on the direct final rule. If we receive any significant adverse comments that warrant terminating the direct final rule, we will consider such comments on the proposed rule in developing the final rule. PMID- 17847578 TI - Medicare program; changes to the hospital inpatient prospective payment systems and fiscal year 2008 rates. AB - We are revising the Medicare hospital inpatient prospective payment systems (IPPS) for operating and capital-related costs to implement changes arising from our continuing experience with these systems, and to implement certain provisions made by the Deficit Reduction Act of 2005 (Pub. L. 109-171), the Medicare Improvements and Extension Act under Division B, Title I of the Tax Relief and Health Care Act of 2006 (Pub. L. 109-432), and the Pandemic and All Hazards Preparedness Act (Pub. L. 109-417). In addition, in the Addendum to this final rule with comment period, we describe the changes to the amounts and factors used to determine the rates for Medicare hospital inpatient services for operating costs and capital-related costs. We also are setting forth the rate of increase limits for certain hospitals and hospital units excluded from the IPPS that are paid on a reasonable cost basis subject to these limits, or that have a portion of a prospective payment system payment based on reasonable cost principles. These changes are applicable to discharges occurring on or after October 1, 2007. In this final rule with comment period, as part of our efforts to further refine the diagnosis related group (DRG) system under the IPPS to better recognize severity of illness among patients, for FY 2008, we are adopting a Medicare Severity DRG (MS DRG) classification system for the IPPS. We are also adopting the structure of the MS-DRG system for the LTCH prospective payment system (referred to as MS-LTC-DRGs) for FY 2008. Among the other policy decisions and changes that we are making, we are making changes related to: limited revisions of the reclassification of cases to MS-DRGs, the relative weights for the MS-LTC DRGs; applications for new technologies and medical services add-on payments; the wage data, including the occupational mix data, used to compute the FY 2008 wage indices; payments to hospitals for the indirect costs of graduate medical education; submission of hospital quality data; provisions governing the application of sanctions relating to the Emergency Medical Treatment and Labor Act of 1986 (EMTALA); provisions governing the disclosure of physician ownership in hospitals and patient safety measures; and provisions relating to services furnished to beneficiaries in custody of penal authorities. PMID- 17847580 TI - Chagas disease: moving towards global elimination. PMID- 17847579 TI - Food labeling: safe handling statements: labeling of shell eggs. Final rule. AB - The Food and Drug Administration (FDA) is amending its food labeling regulations to permit the egg industry to place the safe handling statement for shell eggs on the inside lid of egg cartons if the statement "Keep Refrigerated" appears on the principal display panel (PDP) or information panel. This final rule will provide the industry greater flexibility in the placement of safe handling instructions on egg cartons, while continuing to provide consumers with this important information. This action is in response to numerous requests from the egg industry. PMID- 17847581 TI - [Chemotherapy in lung cancer]. PMID- 17847582 TI - [Recent topics in surgical treatment of lung cancer]. PMID- 17847583 TI - [Radiation treatment of lung cancer]. PMID- 17847584 TI - [Secondary glaucoma associated with bilateral Aspergillus niger endophthalmitis in an HIV-positive patient: case report]. PMID- 17847585 TI - Endocrinology, diabetes, and metabolism. PMID- 17847586 TI - Nurse practitioners in the emergency department. PMID- 17847587 TI - Podiatric medicine and surgery. PMID- 17847588 TI - Pediatric critical care medicine. PMID- 17847589 TI - Abstracts of the Annual Meetings of the Canadian Society of Colon and Rectal Surgeons, the Canadian Association of General Surgeons, and the Canadian Association of Thoracic Surgeons. Canadian Surgery Forum, Toronto, Canada, September 6-9, 2007. PMID- 17847590 TI - [Abstracts of the XXVIII National Congress of the Spanish Society of Nuclear Medicine, Leon, Spain, 13-15 June 2007]. PMID- 17847591 TI - Bibliography. Current world literature. Reproductive endocrinology. PMID- 17847592 TI - Treating HIV-infected infants early prolongs life. PMID- 17847593 TI - [Percutaneous closure of an atrial septal defect]. PMID- 17847594 TI - [Patient education in self management of his treatment]. PMID- 17847595 TI - [Management of pain after a coronary angiography]. PMID- 17847596 TI - [Evaluation of a patient education program for coronary insufficiency]. PMID- 17847597 TI - [Reflections on professional practice in the domain of patient education]. PMID- 17847598 TI - [Ethics, cardiovascular risk factors and prevention]. PMID- 17847599 TI - Emergency contraception for women who have been raped: must catholics test for ovulation, or is testing for pregnancy morally sufficient? AB - On the grounds that tape is an act of violence, not a natural act of intercourse, Roman Catholic teaching traditionally has permitted women who have been raped to take steps to prevent pregnancy, while consistently prohibiting abortion even in the case of rape. Recent scientific evidence that emergency contraception (EC) works primarily by preventing ovulation, not by preventing implantation or by aborting implanted embryos, has led Church authorities to permit the use of EC drugs in the setting of rape. Doubts about whether an abortifacient effect of EC drugs has been completely disproven have led to controversy within the Church about whether it is sufficient to determine that a woman is not pregnant before using EC drugs or whether one must establish that she has not recently ovulated. This article presents clinical, epidemiological, and ethical arguments why testing for pregnancy should be morally sufficient for a faith community that is strongly opposed to abortion. PMID- 17847600 TI - The activities of UNESCO in the area of ethics. AB - The member states of the United Nations Educational, Scientific and Cultural Organization (UNESCO) decided in 2002 that ethics is one of the five priority areas of the organization. This article describes three categories of past and current activities in the ethics of science and technology, in particular bioethics. The first category is the global standard setting with the Universal Declaration on Bioethics and Human Rights as the most recently adopted normative instrument. The second category focuses on capacity building in order to enable member states to apply the provisions of the declarations, through, for example, the establishment of national bioethics committees, the introduction of ethics teaching programs, and drafting of legislation and guidelines. The final category of activities is awareness raising through publications, events, and conferences. The challenges and difficulties UNESCO may face in its various activities are highlighted. PMID- 17847601 TI - Evaluating the therapeutic misconception. AB - The "therapeutic misconception", described by Paul Appelbaum and colleagues more than 20 years ago, refers to the tendency of participants in clinical trials to confuse the design and conduct of research with personalized medical care. Although the "therapeutic misconception" has become a term of art in research ethics, little systematic attention has been devoted to the ethical significance of this phenomenon. This article examines critically the way in which Appelbaum and colleagues formulate what is at stake in the therapeutic misconception, paying particular attention to assumptions and implications that clinical trial participation disadvantages research participants as compared with receiving standard medical care. After clarifying the ethical significance of the therapeutic misconception with respect to the decision making of patients, we offer policy recommendations for obtaining informed consent to participation in clinical trials. PMID- 17847602 TI - Re-evaluating the therapeutic misconception: response to Miller and Joffe. AB - Responding to the paper by Miller and Joffe, we review the development of the concept of therapeutic misconception (TM). Our concerns about TM's impact on informed consent do not derive from the belief that research subjects have poorer outcomes than persons receiving ordinary clinical care. Rather, we believe that subjects with TM cannot give an adequate informed consent to research participation, which harms their dignitary interests and their abilities to make meaningful decisions. Ironically, Miller and Joffe's approach ends up largely embracing the very position that they inaccurately attribute to us: the belief that, with some exceptions, it is only the prospect of poorer outcomes that should motivate efforts to dispel TM. In the absence of empirical studies on the steps required to dispel TM and the impact of such procedures on subject recruitment, it is premature to surrender to the belief that TM must be widely tolerated in clinical research. PMID- 17847603 TI - Pharmacists and conscientious objection. PMID- 17847604 TI - Real-time updates of meta-analyses of HIV treatments supported by a biomedical ontology. AB - Meta-analyses involve a systematic statistical explanation of available evidence and are a commonly used systematic reviewing strategy for addressing health related scientific research. Publication biases often delay reporting of meta analyses and subsequent policy making. Ontologies have the capacity to provide real time meta-analyses that can reduce publication delay. The purpose of this study was to describe the meta-analytic process of a recently revised ontology. Three recently published meta-analyses were replicated using an ontology that extracts appropriate statistical "tags" from the originally reviewed published manuscripts. The ontology was able to closely represent the findings of the original meta-analysis including funnel, forest, and summary statistics. The use of an ontology could improve the speed in which meta-analytic publications occur as well as potentially standardizing the required elements within a randomized controlled trial. The findings in this study demonstrate similar ontological output as used in the Trial Bank Project with decreased time requirements of the manuscript author and the software programmers. The use of an ontology may improve the reporting of meta-analysis and, when combined with an open access website, should assist in timely policy-making decisions by healthcare providers. PMID- 17847605 TI - Pediatric research posing a minor increase over minimal risk and no prospect of direct benefit: challenging 45 CFR 46.406. AB - Subpart D of the Common Rule establishes 4 categories of research that may be conducted on children. One category, 45 CFR 46.406, permits research posing a minor increase over minimal risk and no prospect of direct benefit but expected to yield vital knowledge about the subjects' disorder or condition. To include other children in research posing a minor increase over minimal risk and no prospect of direct benefit requires federal review and approval of the Secretary of Health and Human Services under 45 CFR 46.407. It is widely held that children generally should not be exposed to more than minimal risk in research without the prospect of direct benefit. To justify deviating from this norm, as 406 allows, two claims must be true: (1) When there is vital knowledge to be gained from studying children, it is permissible to expose some children to a minor increase over minimal risk with no prospect of direct benefit; (2) It is permissible for locally reviewed and approved research to expose only children with the disorder or condition under investigation to greater risk with no prospect of direct benefit. The justification for (1) appears to be grounded in the magnitude of benefit to society combined with the need to study children. This article demonstrates that, even if the necessity and magnitude of benefit to society justify exposing children to increased risk, the decision to categorically restrict participation in such research to children with the disorder or condition under investigation (unless the study is federally reviewed and approved) is not justified. Subpart D should be revised. PMID- 17847606 TI - Intentional exposure studies of environmental agents on human subjects: assessing benefits and risks. AB - In this article, I assess the benefits and risks of studies that intentionally expose research subjects to environmental agents. I describe these types of studies, identify their benefits and risks, compare them to other research methods that can be used to investigate the relationship between environmental exposures and disease, and discuss some issues related to research design and risk minimization. I argue that the benefits of intentional environmental exposure studies outweigh the risks when 1) the knowledge gained is likely to improve our understanding of the relationship between environmental exposure and disease, 2) this knowledge cannot be obtained by other methods, 3) the experiments are well designed, 4) the subjects will receive some benefits, such as medical evaluations, 5) risks are minimized, and 6) the risks to human subjects are less than those encountered in a typical Phase I drug study. Only in rare circumstances (i.e., when an intentional environmental exposure study is needed to implement an important environmental or public health intervention or regulation) may such studies expose research subjects to risks as high as those encountered in a typical Phase I drug trail. PMID- 17847607 TI - Research records and the resolution of misconduct allegations at research universities. AB - Accurate record keeping is an important part of the responsible conduct of research. However, there is very little empirical research on scientific record keeping. No one knows the incidence of serious problems with research records, the types of problems that occur, nor their consequences. In this study, we examined the role of research records in the resolution of misconduct allegations as a useful barometer for the incidence and types of problems that occur with records. We interviewed Research Integrity Officers (RIOs) at 90 major research universities and conducted focus groups with active research faculty. RIOs reported problems with research records in 38% of the 553 investigations they conducted. Severe problems with research records often prevented completion of investigations while problems that are more typical lengthened them by 2 to 3 weeks. Five types of poor record keeping practices accounted for 75 % of the problems with incomplete/inadequate records being the most common (30%). The focus groups concurred with the findings from the interviews with RIOs, stressed the importance of the research group leader in setting and maintaining record practices, and offered additional insights. While university officials and faculty members have suspected for many years that there are serious problems with research record keeping, our study provides empirical evidence for this belief. By documenting some of the problems with record keeping in university based research, the results of our study provide information that will be useful for policy development at academic institutions. PMID- 17847608 TI - Ethical issues in cancer chemoprevention trials: considerations for IRBs and investigators. PMID- 17847609 TI - Determining the costs of Institutional Review Boards. PMID- 17847610 TI - Deception in the single-blind run-in phase of clinical trials. PMID- 17847611 TI - Sir Ara sets out london vision for cradle-to-grave healthcare. PMID- 17847612 TI - HSE clears infection death managers. PMID- 17847613 TI - Hewitt should not be a patsy for the health service's mistakes. PMID- 17847614 TI - On the power of targets. PMID- 17847615 TI - Demand management. Is this really the end of under-capacity? PMID- 17847616 TI - Barometer. Mental health June 2007. PMID- 17847617 TI - Local accountability. Panel discussion. PMID- 17847618 TI - Older people. A milestone in self-management. PMID- 17847619 TI - Staff engagement. Mind over matter. PMID- 17847621 TI - Informed consent for dementia research: the study enrollment encounter. PMID- 17847620 TI - Who should go first in trials with scarce agents? The views of potential participants. PMID- 17847623 TI - Creating new career opportunities in occupational health nursing. Interview by Eileen Lukes. PMID- 17847622 TI - Does size matter? Salience of follow-up payments in drug abuse research. PMID- 17847624 TI - Registered nurses' self-nurturance and life and career satisfaction. AB - Knowledge of factors that help nurses thrive, including satisfaction with life and self-nurturance, can be used to enhance retention of a healthy work force. This study determined whether nurses are happy or satisfied with their lives; how self-nurturing or "good to self" they are; and whether a relationship exists among self-nurturance, life satisfaction, and career satisfaction. A descriptive, correlational study of 136 registered nurses involving measures of self nurturance and life and career satisfaction was conducted. Mean scores for life satisfaction and self-nurturance were consistent with those from studies of well adults. Self-nurturance, life satisfaction, and career satisfaction were positively correlated with each other; thus, improving one is expected to improve the others. Knowledge of the significant positive correlation among life satisfaction, self-nurturance, and career satisfaction may prove useful in improving the mental health and safety of nurses. Strategies consistent with Magnet hospital characteristics are suggested for the occupational health nurse. PMID- 17847625 TI - Hazardous decibels: hearing health of firefighters. AB - Noise-induced hearing loss ranks among the most significant occupational health problems. In the United States, more than 1 million firefighters are at risk for noise-induced hearing loss due to exposure to hazardous levels of intermittent noise from sirens, air horns, and engines of emergency vehicles and fire trucks. Although irreversible, noise-induced hearing loss is entirely preventable through both engineering controls and personal protective equipment. This article describes occupational noise exposure, hearing loss, and strategies to prevent noise-induced hearing loss among firefighters. PMID- 17847626 TI - Identifying health and safety risks for childcare workers. AB - Childcare workers are exposed to several health and safety risks in their work environment, the most common being infectious diseases, musculoskeletal injuries, accidents, and occupational stress. Pregnant childcare workers have an additional risk of potential harm to the fetus. Occupational health nurses can work collaboratively with childcare workers to reduce these risks and provide workplace health promotion programs. This article explores the occupational health and safety issues for childcare workers and suggests health promotion strategies that could be implemented by occupational health nurses working in this arena. PMID- 17847627 TI - Providing leadership in a culturally diverse workplace. AB - Cultural diversity is an increasingly important characteristic of the work force. Occupational health nurses with sensitivity to the influence of culture on behavior and knowledge of strategies to deliver culturally competent services can lead to and/or help develop a culturally sensitive health care environment and influence corporate culture and policies. PMID- 17847628 TI - Ears and air travel. AB - Frequent flyer business travelers experience recurrent ear problems. Common causes and prevention are discussed. PMID- 17847629 TI - The autonomy axiom and the cloning of humans. PMID- 17847630 TI - The morning-after pill. PMID- 17847631 TI - Genetic medicine: Polish deontological guidelines and the ethical practice of research studies with children. AB - The purpose of the article is: (1) to describe deontological guidelines which regulate medical research involving human subjects in Poland, and (2) to clarify the understanding of the fundamental ethical concepts presented in these documents. To do this, two main documents are analysed: (1) the Polish Medical Ethics Code, which was approved by the 7th Extraordinary National Doctors' Convention in September 2003 after a long and difficult process of revision, and (2) the Good Practice in Science, a set of rules concerning scientists, approved by the Committee of Ethics of the Polish Academy of Science in 2001. The pluralism of contemporary ethics and of medical ethics in particular, results in various interpretations of the understanding of the crucial terms used in the deontological statements of these codes. The paper suggests that clarity in the understanding of the terms may be achieved by exploring the 'intellectual' context in which the analysed documents have been appearing and in which they are presently functioning. In order to examine such a context, the following aspects are taken into account: (1) the development of bioethics as a discipline in Poland, (2) international deontological documents which are universally accepted and are in use in Poland, (3) legal regulations regarding medical research involving persons which are currently in force in Poland, and (4) the practice of Polish Institutional Review Boards (IRBs). PMID- 17847632 TI - The indispensability of quality of life. AB - Is a value-judgement of human quality of life permissible, especially in view of the possibility of wishing to intentionally terminate this human life? In German bio-politics, this issue tends to be evaded. Problems that increasingly arise at the end as well as the beginning of a human life, however, render the discussion inevitable. In this context, the assumption that, as a matter of principle, judging the value of quality of life is incompatible with the concept of human dignity plays a central part. This premise would indicate that bio-ethical and bio-political debate threatens to revert to a state of rigid confrontation of factions that are both inflexible and unable to communicate. PMID- 17847633 TI - Moral and ethical issues in gene therapy. PMID- 17847634 TI - Significant developments in stem cell research. PMID- 17847635 TI - Third-party risks in research: should IRBs address them? PMID- 17847636 TI - The many ways of saying yes and no: reflections on the research coordinator's role in recruiting research participants and obtaining informed consent. PMID- 17847637 TI - Monitoring reportable events and unanticipated problems: the PHAROS and PREDICT studies of Huntington disease. PMID- 17847638 TI - First impressions: the experiences of a community member on a research ethics committee. PMID- 17847639 TI - Automated margin analysis of contemporary adhesive systems in vitro: evaluation of discriminatory variables. AB - PURPOSE: Using an optical sensor, to automatically evaluate the marginal seal of restorations placed with 21 adhesive systems of all four adhesive categories in cylindrical cavities of bovine dentin applying different outcome variables, and to evaluate their discriminatory power. MATERIALS AND METHODS: Twenty-one adhesive systems were evaluated: three 3-step etch-and-rinse systems, three 2 step etch-and-rinse systems, five 2-step self-etching systems, and ten 1-step self-etching systems. All adhesives were applied in cylindrical cavities in bovine dentin together with Tetric Ceram (n=8). In the control group, no adhesive system was used. After 24 h of storage in water at 37 degrees C, the surface was polished with 4000-grit SiC paper, and epoxy resin replicas were produced. An optical sensor (FRT MicroProf) created 100 profiles of the restoration margin, and an algorithm detected gaps and calculated their depths and widths. The following evaluation criteria were used: percentage of specimens without gaps, the percentage of gap-free profiles in relation to all profiles per specimen, mean gap width, mean gap depth, largest gap, modified marginal integrity index MI. The statistical analysis was carried out on log-transformed data for all variables with ANOVA and post-hoc Tukey's test for multiple comparisons. The correlation between the variables was tested with regression analysis, and the pooled data accordingto the four adhesive categories were compared by applying the Mann-Whitney nonparametric test (p < 0.05). RESULTS: For all the variables that characterized the marginal adaptation, there was a great variation from material to material. In general, the etch-and-rinse adhesive systems demonstrated the best marginal adaptation, followed by the 2-step self-etching and the 1-step self-etching adhesives; the latter showed the highest variability in test results between materials and within the same material. The only exception to this rule was Xeno IV, which showed a marginal adaptation that was comparable to that of the best 3-step etch-and-rinse systems. Except for the variables "largest gap" and "mean gap depth", all the other variables had a similar ability to discriminate between materials. Pooled data according to the four adhesive categories revealed statistically significant differences between the one-step self-etching systems and the other three systems as well as between two-step self-etching and three-step etch-and-rinse systems. CONCLUSIONS: With one exception, the one-step self-etching systems yielded the poorest marginal adaptation results and the highest variability between materials and within the same material. Except for the variable "largest gap", the percentage of continuous margin, mean gap width, mean gap depth, and the marginal integrity index MI were closely related to one another and showed--with the exception of "mean gap depth"--similar discriminatory power. PMID- 17847640 TI - Microrotary fatigue resistance of a HEMA-free all-in-one adhesive bonded to dentin. AB - PURPOSE: To determine the effect of thorough air drying on the static and dynamic bonding effectiveness of a HEMA-free all-in-one adhesive bonded to Class-1 cavity bottom dentin. MATERIALS AND METHODS: G-Bond (GC, Japan) was applied to standard occlusal Class I cavities following either a gentle (1 bar) or strong (4 bar) air drying technique. After restoring the cavity using a composite resin (Gradia Anterior, GC), microspecimens were prepared that were loaded until failure or inserted in a microrotary fatigue testing device. RESULTS: Strong air drying had no effect on the static (39.1 vs. 38.4 MPa) or the dynamic (19.0 vs. 18.6 MPa) strength of the interface complex. CONCLUSION: Strong air drying did not improve the static or the dynamic bonding effectiveness, although a very thorough (4 bar) and long air-drying procedure was employed. SEM analysis revealed that even when the adhesive was strongly air dried, droplets originating from phase separations could still be observed, albeit to a reduced extent. Ineffective drying and pooling of the adhesive in a narrow cavity diminished the effect of strong air drying of the all-in-one adhesive. PMID- 17847641 TI - The effect of different air-polishing powders on dentin bonding. AB - PURPOSE: Air-polishing is routinely used for professional tooth cleaning. Therefore, the aim of this in vitro study was to evaluate the influence of different air-polishing powders on dentin bonding. MATERIALS AND METHODS: Dentin bond strengths of a resin composite (Clearfil AP-X) bonded with different classes of adhesives (4-step etch-and-rinse: Syntac; 3-step etch-and-rinse: OptiBond FL; 2-step etch-and-rinse: Single Bond Plus; 2-step self-etching: AdheSE, Clearfil SE Bond, Clearfil Protect Bond, One Coat Self-Etch Bond; all-in-one/mix: Xeno III; all-in-one/no mix: Clearfil S3 Bond, G-Bond) were measured on flattened dentin surfaces. In test groups, specimens were air polished with Prophypearls (calcium carbonate) or ClinPro Prophypowder (glycine) prior to bonding. Microtensile bond strengths were evaluated after 24 h of storage at 37 degrees C in water. Surfaces and resin-dentin interfaces were observed by SEM, TEM, and CLSM. RESULTS: Mean bond strengths varied from 18 to 73 MPa in control groups. Calcium carbonate air polishing generally caused significantly reduced dentin bond strengths (p < 0.05). TEM exhibited severe nanoleakage after calcium carbonate air polishing. Glycine did not affect dentin bonding performance of the adhesives under investigation. CONCLUSION: Calcium carbonate air polishing should be avoided when dentin-bonded restorations are applied. Glycine powder is an alternative. PMID- 17847642 TI - Effect of air-drying temperature on the effectiveness of silane primers and coupling blends in the repair of a microhybrid resin composite. AB - PURPOSE: To evaluate the effect of different silane agents and air-drying temperatures on the repair strength of a microfilled hybrid composite. MATERIALS AND METHODS: Composite cylinders (8 x 4 mm) of Gradia Direct Anterior (GC, N=36), stored in a saline solution at 37 degrees C for 1 month, were sandblasted (50 microm aluminium oxide), cleaned (35% phosphoric acid) and randomly divided into six groups (n=6). Two prehydrolyzed silane primers (Monobond-S, Ivoclar-Vivadent, Porcelain Primer, Bisco), a non prehydrolyzed silane primer (Porcelain Liner M, Sun Medical) and three silane/adhesive coupling agents (Porcelain Bond Activator PBA/Clearfil New Bond, PBA/Clearfil SE Bond, PBA/Clearfil Tri-S Bond, Kuraray) were investigated. Silane-coated surfaces were air dried at two different temperatures (23 degrees C and 38 degrees C) and repairs (8 x 8 mm) were fabricated (Gradia Direct Anterior). Unrepaired composite cylinders (8 x 8 mm, n=6) were used as control to evaluate the cohesive strength of the material. Microtensile bond strength measurements (microTBS) were performed. RESULTS: The silane agent applied (p < 0.001), the airdrying temperature (p < 0.001) and their interaction (p < 0.001) were significant factors (two-way ANOVA, Tukey test; p < 0.05). Silane primers achieved inferior microTBS when air dried at 23 degrees C as compared to silane/adhesive blends. Warm air-drying was significantly beneficial to composite repairs mediated by silane primers. Comparable results were achieved by silane/adhesive couplings at 23 degrees C and 38 degrees C. At 38 degrees C all the intermediate agents resulted in repair microTBS that were comparable to the 24-h cohesive strength of the composite (one-way ANOVA, Dunnett t-tests; p < 0.05). CONCLUSION: The chemical interactions between silane primers and compozite substrate may be optimized through warm airdrying. Silane/adhesive couplings were not influenced by the air drying temperature. PMID- 17847643 TI - Effect of physicochemical aging conditions on the composite-composite repair bond strength. AB - PURPOSE: This study evaluated the effect of different physicochemical aging methods and surface conditioning techniques on the repair bond strength of composite. It was hypothesized that the aging conditions would decrease the repair bond strength and surface conditioning methods would perform similarly for the repair of resin composites. MATERIALS AND METHODS: Disk-shaped resin composite specimens (Clearfil Photo Bright, Kuraray) were randomly assigned to one of the three aging conditions (N=120, n = 12/per group): (1) immersion in deionized water (37 degrees C, 1 week), (2) immersion in citric acid (pH: 3.0, 1 week), (3) boiling in water (8 h), (4) thermocycling (5000 times, 5 degrees C to 55 degreesC), (5) immersion in water (37 degrees C, 2 months). After aging procedures, the specimens were subjected to one of the following surface conditioning methods: (1) chairside silica coating (30-microm SiOx) (CoJet, 3M ESPE) + silane (ESPE-Sil) (SC method), (2) silane (Clearfil SE Bond Primer and Clearfil Porcelain Bond Activator) + bonding agent (Clearfil SE Bond) (SB method). The fresh and aged composite surfaces were also examined using SEM (n=6, 1/group). Resin composite (Quadrant Anterior Shine) was bonded to the conditioned substrates using polyethylene molds and then light polymerized. Shear force was applied to the adhesive interface in a universal testing machine (1 mm/min). The failure types were categorized as: (A) cohesive in the substrate, (B) adhesive at the interface, or C) cohesive in the adherend. Bond strength values were statistically analyzed using two-way ANOVA and Tukey's test (alpha < 0.05). RESULTS: A significant influence of the conditioning method (p < 0.0001) and aging method was observed (p < 0.01) (two-way ANOVA, Tukey-Kramer). The SC method showed significantly higher bond values (7.8 +/- 1.2 to 11.6 +/- 5 MPa) than those of SB method (4.6 +/- 2.3 to 7.6 +/- 3.9 MPa) in all groups (p < 0.0001). While the SC method showed 96% cohesive (A type), the SB method demonstrated 92% adhesive failures (B type). SEM images showed distinct pattern of microcracks in the boiled specimens and filler dissolution with disorganized matrix resin in the other aged specimens. Aging the composite substrates through water storage for 2 months produced significantly lower bond strengths than those of water or acid storage for 1 week (p = 0.011). CONCLUSION: Chairside silica coating and silanization provided the highest bond strength values with almost exclusively cohesive failures on aged composites. Aging methods showed significant differences on the composite-composite repair strength. PMID- 17847644 TI - Influence of surface characteristics of four silica-based machinable ceramics on flexural strength and bond strength of a dual-curing resin luting agent. AB - PURPOSE: The aim of the present study was to evaluate the crystalline phase and microstructure of 4 commercial machinable ceramic blocks--Cerec Vitablocs Mark II (Vita), ProCAD (Ivoclar/Vivadent), GN-I (GC), and GNCeram (GC)--and compare flexural strength and shear bond strength between a dual-curing resin luting agent and the ceramics treated with a silane coupling agent. MATERIALS AND METHODS: Specimens were examined using scanning electron microscopy/energy dispersive x-ray spectroscopy, and x-ray diffractometry. Three-point bending tests were performed with polished specimens 20 mm long, 4 mm wide, and 1.2 mm thick. Two differently shaped specimens for each of the 4 machinable ceramics were treated with a silane coupling agent. The specimens were then cemented together with a dual-curing resin luting agent. Half of the specimens were stored in water at 37 degrees C for 24 h and the other half were thermocycled 20,000 times. RESULTS: Chemical composition, crystalline phase, and crystallinity were significantly different between brands. The Vitablocs Mark II material had the significantly lowest flexural strength (101.7 +/- 15.3 MPa), while the GNCeram material had the highest (174.8 +/- 10.3 MPa). The use of a silane coupling agent yielded high shear bond strength after 20,000 thermocycles (Vitablocs Mark II: 37.7 +/- 3.7 MPa, ProCAD: 41.2 +/- 3.1 MPa, GNCeram: 50.2 +/- 2.1 MPa), except with the GN-I material (23.9 +/- 4.4 MPa). CONCLUSION: It appeared that crystal distribution and particle size of leucite crystal, not crystallinity, in the feldspar glass matrix of silica-based machinable ceramics might influence the flexural strength and efficacy of a silane coupling agent in bonding between a dual-curing resin luting agent and machinable ceramics. PMID- 17847645 TI - The emerging role of PAs in the hospitalist movement. PMID- 17847646 TI - CVI and PAD: a review of venous and arterial disease. PMID- 17847647 TI - Papulosquamous rash in a man with HIV disease. PMID- 17847648 TI - Lumbar ADR: a triumph of technology over reason? AB - The many unanswered questions surrounding ADR beget the question of whether patients would ultimately be better managed with lumbar fusion surgery or even no surgery at all. Lumbar fusion technology has made advances in recent years with the advent of transforaminal lumbar interbody fusion (TLIF) and the use of bone morphogenetic proteins. With a TLIF procedure, spine surgeons are able to obtain a 360-degree fusion through a single posterior incision with more predictable long-term results, especially when patients have confounding issues. Although early clinical results show ADR to be a promising alternative to current surgical options, long-term results are needed to adequately assess the procedure's efficacy. There will always be a demand for new technology. Cost, quality, and access are performance benchmarks for hospital survival in the current health care industry. Today's health care environment forces surgeons to be fiscally responsible while still providing the best quality care possible. Therefore, the cost of ADR compared to a traditional pedicle screw instrumentation (about $12,000 per segment vs $3,500 per segment) must be taken into consideration. Is the additional cost of ADR justified when studies so far fail to show a statistically significant difference in long-term outcomes? How do we justify the added cost when conventional lumbar fusion, the gold standard for intractable cases, has more predictable outcomes? Ultimately, ADR may be a more promising alternative to spinal fusion for patients with multilevel DDD (ie, a three segment lumbar disk replacement) because it can spare disk decompensation of the adjacent segments. PMID- 17847649 TI - Depression in older patients: recognition and treatment. PMID- 17847650 TI - Breast cancer: 1987 and 2007. PMID- 17847651 TI - The duty to treat and the realities of the 21st century. PMID- 17847652 TI - What caused this UTI in a 3-year-old girl? PMID- 17847653 TI - Case of the month. Obstipation. PMID- 17847654 TI - Medication errors and syringe safety are top concerns for nurses according to new national study. PMID- 17847655 TI - The impact of stress management on nurse productivity and retention. AB - Throughout the history of nursing there is a seeming legacy of personnel shortage, lack of funds, and, based on the nature of the role and related services, heightened levels of stress involved in patient care. The future of the profession, and more imminently, patient care and the health of nurses, may be significantly impacted by repeated challenges where current levels of stress and burnout are contributing to organizational problems, burnout, and attrition. Employee stress and burnout commonly lead to myriad health-related problems that result in significant organizational consequences. There are many methods of stress management, and sometimes the best and most effective begin with simple recognition, validation, and visible and committed efforts by the nurse executive. Regardless of the technique or approach, what is clear is that there is a need for nurse executives to include the development and enhancement of comprehensive stress-management programming for employees as a priority item to avoid burnout and attrition. PMID- 17847656 TI - The implications of nurse staffing information: the real value of reporting nursing data. AB - There is a dearth of information about the relationship between the patient care contributions of nursing and its financial contributions to an organization. As consumers and legislators are becoming more aware of the ramifications of nurse staffing issues, and as they endeavor to address them with legislative solutions, the decision on how best to develop optimal staffing strategies may soon be taken away from nursing leaders. To maintain control of this important issue and develop solutions that will help highlight the economic and patient care contributions of nurses, a thorough understanding of the problem, and a new commitment are needed from nursing leaders to take charge of the issue. To relate nursing care to patient outcomes, meaningful data on the nursing care provided is needed in addition to data on the nursing needs of patients. Staffing and performance monitoring tools should be used to effectively plan, implement, and control financial and operating resources as well as measure the economic value of the nursing profession's contribution to the cost and benefits of patient care. PMID- 17847657 TI - Moral distress: recognizing it to retain nurses. AB - Faced with the challenges in today's acute care environment, 15% of the nurses in one study reported resigning a position due to experiencing moral distress. Moral distress is the physical or emotional suffering that is experienced when constraints (internal or external) prevent one from following the course of action that one believes is right. With more responsibility than authority, nurses often lack the autonomy to do what they feel should be done. Nurses often seem unaware of moral distress experience in themselves. Feelings labeled as stress, burnout, emotional exhaustion, and job dissatisfaction may actually be symptomatic of moral distress. An organizational commitment to addressing the issue of moral distress could reap benefits with greater employee job satisfaction, decreased turnover, and ultimately improved patient care. PMID- 17847658 TI - Conceptual frameworks used in funded nursing health services research projects. AB - Theories not only suggest ideas for research, but they provide order and logic to an investigation and limit the number and type of variables to be considered to a reasonable few. Although relatively little health services research is done within nursing, there is a growing appreciation of the need for knowledge related to the use, costs, quality, delivery, organization, financing, and outcomes of health care and how nursing practice influences these variables. Conceptual frameworks used by investigators in funded grants from the Agency for Healthcare Research and Quality show that workforce-related health services research of nursing phenomena is based on a wide variety of conceptual models, many of the investigator's own invention. Ultimately, there may emerge new theories or conceptual frameworks that combine clinical, organizational, financial, and outcome variables from the unique perspective of nursing. Such conceptualizations will guide future researchers and add coherence to the body of health services research into nursing issues. PMID- 17847659 TI - Onboarding: delivering on the promise. AB - The nursing workforce continues to age and exit the workplace. U.S. Bureau of Labor Statistics studies indicate as many as 40% will retire or are considering retirement. Fewer qualified graduates are in place to replace aging baby boomers, leading to a knowledge and skills gap as well as a numbers gap. Globalization of the nursing workforce has increased competition for all employers to find, hire, and retain good employees. PMID- 17847660 TI - Using technology to let your voice be heard. AB - Creating e-mail audio messages can add a more personal touch to your communications with staff and possibly build loyalty while affirming your interest and concern for your employees. A 5-minute flash demonstration of this process, which should play in any Internet browser, can be viewed at http://tigger.uic.edu/~mcassey/neja07/neja07.html. Learning to use high tech to promote an experience of high touch is a frequently missed opportunity in the business of health care delivery. PMID- 17847661 TI - Leadership, civility, and the 'No Jerks' rule. AB - Nursing organizations and hospitals are not immune from the ravages of incivility. Toxic behavior can range from the very serious bullying and sabotage of very destructive people to the annoying and hard to cope behavior of just plain jerks. When a unit does not have a clearly defined "No Jerk" rule and infrastructure to support healthy behavior, communication suffers and errors occur. Nurse leaders have the opportunity of changing the self-interest behavior of jerks in our communities of caring. PMID- 17847662 TI - Immigration and health care reform: shared struggles. AB - The connection between health care and immigration share overlaping key areas in policy reform. General concern, anger, and fear about immigration has been spreading nationwide. While illegal immigrants' use of expensive emergency department services does add to the cost for uncompensated care, this expenditure is not a primary cost driver but more a symptom of little or no access to preventative or primary health care. As a result of federal inaction, more state politicians are redefining how America copes with illegal residents including how or whether they have access to health care. The overlap of immigration and health care reform offers an opportunity for us to enter the next round of debate from a more informed vantage point. PMID- 17847663 TI - Career coaches for nursing: a strategy for increasing your ROI. AB - Career Coaches for Nursing was created as an innovative program for the nursing staff at a large, expanding Midwestern tertiary health care organization. In the 2-year start-up period, the new program met challenges and identified many system wide, as well as local issues for improvement. A decrease in turnover and the associated cost savings from improved employee retention provided a positive return on investment within the first 2 years of the program's existence. PMID- 17847664 TI - Centers of excellence: getting on the bandwagon. PMID- 17847665 TI - Fever management practices of neuroscience nurses, part II: nurse, patient, and barriers. AB - Fever is frequently encountered by neuroscience nurses in patients with neurological insults and often results in worsened patient outcomes when compared with similar patients who do not have fever. Best practices in fever management are then essential to optimizing patient outcomes. Yet the topic of best nursing practices for fever management is largely ignored in the clinical and research literature, which can complicate the achievement of best practices. A national survey to gauge fever management practices and decision making by neuroscience nurses was administered to members of the American Association of Neuroscience Nurses. Results of the questionnaire portion of the survey were previously published. This report presents a content analysis of the responses of neuroscience nurses to the open-ended-question portion of the survey (n = 106), which revealed a dichotomous primary focus on nursing- or patient-related issues. In addition, respondents described barriers and issues in the provision of fever management care to neuroscience patients. In order to advance national best practices for fever management in neurologically vulnerable patients, further work needs to be conducted, particularly with regard to necessary continuing education for staff, facilitation of interdisciplinary communication, and development of patient care protocols. Neuroscience nurses are in an excellent position to provide leadership in these areas. PMID- 17847666 TI - Recognizing involuntary emotional expression disorder. AB - Involuntary crying or laughing are symptoms of a condition known as involuntary emotional expression disorder (IEED). This disorder is common among patients with stroke and other neurological disorders, such as multiple sclerosis, amyotrophic lateral sclerosis, and traumatic brain injury. Despite its prevalence, this condition is underrecognized and consequently undertreated in neurological settings. IEED can become disabling for patients who are not accurately diagnosed and treated. Differential diagnosis depends on recognition of the condition as an affective disorder and on its delineation from unipolar depression and other major psychiatric disorders. Clinical evaluation is essential for effective nursing care of this disorder. When the condition is found to be present, effective management must include education, pharmacological treatment, and teaching of self-care strategies. As patient advocates, neuroscience nurses are in a unique position to identify and assess such patients and to effectively guide patients and families in the management of this condition. PMID- 17847667 TI - Acute disseminated encephalomyelitis. AB - Acute disseminated encephalomyelitis (ADEM) is a monophasic, demyelinating disease of the central nervous systemthat predominately affects prepubertal children. It is typically characterized by an abrupt onset of neurologic symptoms preceded by an infection or recent immunization. ADEM is a diagnosis of exclusion in many cases, though the differential diagnosis is extensive. An adult female diagnosed with ADEMrepresents an atypical presentation; she was subsequently treated successfully with high-dose steroids. Nursing considerations for patients with ADEM include teaching patients and families about the disease, its clinical course, treatment, and prognosis. PMID- 17847668 TI - The impact of migraine: a case study. AB - Migraine headaches are common and among the most disabling nonfatal conditions of humankind. They are frequently misdiagnosed, which may lead to undertreatment. Patients often self-diagnose and self-medicate, resulting in inadequate treatment. Consequently, patients may take additional doses, trying to gain relief with inappropriate medications. Rebound can ensue. With adequate treatment, a patient's condition and quality of life may improve considerably. Patient education is extremely important to help patients identify appropriate self-care measures, such as identification of triggering events and coping with the chronic nature of their condition. This case study presents a patient who began experiencing migraines following a neck injury. His headaches became more frequent, and ergotamine and caffeine (Cafergot) suppositories were prescribed. When he presented, he was experiencing daily headaches and using daily ergotamine and caffeine suppositories. He was using the emergency department (ED) frequently because of severe headaches. Cervical spasm was recognized as his trigger, and the ergotamine and caffeine suppositories were discontinued. After 3 days of severe headaches, his rebound ceased. He reverted back to episodic migraines, which he treated with zolmitriptan (Zomig) nasal spray, which was effective. His cervical spasm was treated with botulinum toxin type A (Botox), with excellent results. He has maintained reasonable headache control for 2 years. PMID- 17847669 TI - A comparison of working versus nonworking family caregivers of stroke survivors. AB - Because of the trend toward shorter hospital stays, family caregivers of stroke survivors are expected to accept more responsibility for helping survivors during the subacute recovery process. The caregiver role is associated with negative health outcomes, yet existing literature differs on whether work status is a contributor. The purpose of this secondary analysis was to examine how caregiving affects employment and to compare characteristics of working and nonworking caregivers. Baseline data of family caregivers (N = 132) caring for stroke survivors 3-9 months after stroke and enrolled in a national multisite study were used. Caregiver characteristics of physical health, depression, fatigue, family functioning, and family conflict were measured. A total of 36% of caregivers reduced their work hours, resigned, or retired from their jobs to care for their family member. A larger proportion (n = 25, 66%) of minority caregivers were employed (full time or part time) compared to white caregivers (n = 43, 46%). Caregivers employed full time were younger and in better physical health but were at higher risk for depressive symptoms than nonworking caregivers. Family function and conflict were similar between the groups, but working caregivers received more assistance from other family members. Healthcare professionals and employers can use these findings to assist them with recognizing the needs of employed caregivers and offering support measures to facilitate their dual role. PMID- 17847670 TI - Cognitive remediation therapies for older adults: implications for nursing practice and research. AB - Among older adults, 20%-56% report having cognitive problems, and such cognitive complaints frequently correspond to actual neuropsychological impairment. The loss of cognitive abilities can be frustrating and frightening and can have a negative impact on instrumental activities of daily living and quality of life. Cognitive remediation interventions have been shown to be successful in improving mental function in older adults in many situations and may increase the number of everyday activities they are able to carry out. Nurses, given their direct contact with older adult patients, are able to inquire about or observe cognitive loss, make appropriate referrals, and emphasize steps such as cognitive remediation and other interventions that promote successful cognitive aging. PMID- 17847671 TI - Stroke versus primary CNS lymphoma in the immunocompromised patient. AB - Primary central nervous system (CNS) lymphomas are an uncommon form of brain neoplasm that should be considered in the immunocompromised patient with neurological changes. It can be difficult to distinguish primary CNS lymphoma from stroke on initial radiographic images. Neuroscience nurses who are involved in the care of these patients should be prepared to assist the patient and family in coping with an evolving diagnosis and in explaining the related diagnostic procedures, treatment options, and eventual discharge plan. PMID- 17847672 TI - FAST Stroke Prevention Educational Program for Middle School Students: pilot study results. AB - This pilot study evaluated the effects of FAST Stroke Prevention Educational Program for Middle School Students, a 2-month stroke prevention educational program targeted to middle school students. The FAST program focused on improving knowledge of stroke signs and symptoms; risk factors; treatment-seeking behaviors (call 911); overall attitude toward stroke, including perceived self-efficacy in identifying stroke warning signs and dealing with a stroke victim; stroke risk reduction behaviors; and other risk factors for stroke, such as hypertension and diabetes. The FAST program evaluation consisted of a pretest, an educational intervention, immediate posttest, and a long-term posttest at 2 months. A convenience sample of 72 students with a mean age of 13.25 years was used. After obtaining school, parental, and student consent, the FAST program was implemented by the school nurse, health teachers, and research nurses. Results indicated significant increases in knowledge of stroke risk factors and warning signs and in attitudes of self-efficacy among middle school students that were sustained from pretest to long-term posttest; data supported the effectiveness of this novel intervention. Additional research using a variety of educational strategies and a longer time frame of intervention is recommended to further expand use of this program. PMID- 17847673 TI - Job satisfaction among multiple sclerosis certified nurses. AB - Several studies document high levels of job satisfaction among certified nurses, but no study has examined job satisfaction and factors influencing job satisfaction of certified multiple sclerosis (MS) nurses. This study tested a theoretical model proposing that two organizational factors, colleague relationships and benefits, will predict job satisfaction. Job satisfaction was represented by four factors: autonomy, professional status, professional growth, and time efficiency. Participants included MS nurses certified for 6 months or more practicing mostly in three countries (Canada, Great Britain, and the United States) who anonymously completed the Misener Nurse Practitioner Job Satisfaction Scale, an overall job satisfaction rating, and demographic information. Findings indicate that colleague relationships and benefits significantly estimated organization structure and that autonomy, professional status, professional growth, and time efficiency significantly estimated job satisfaction; furthermore, organization factors such as colleague relationships and benefits significantly predict job satisfaction. Among the countries, several statistically significant differences were observed between job satisfaction factors as well as items in both organization and job satisfaction subscales. Average factor scores among the countries were mostly rated satisfactory. The International Organization of Multiple Sclerosis Nurses Executive Board plans to use the study findings to see how it needs to focus efforts as an organization toward enhancing and standardizing MS care and develop MS nurse professionalism worldwide. PMID- 17847674 TI - Development of a new procedure for the application of microwave energy during marble slab production. AB - In this work a new microwave-heating procedure is presented as a viable alternative for both the conventional and ultraviolet (UV) curing systems used in the natural stone industry. Both thermal simulations and experimental tests demonstrate that microwave energy highly reduces curing and storing times while maintaining the product's final quality. Several polymer mixtures have been obtained from commercial products and fillers for maximum microwave absorption and their complex permittivity has been properly measured. A continuous industrial microwave oven has been built specifically for this purpose and tested on Crema-Sierra Puerta marble samples and commercial epoxy and polyester resins. PMID- 17847675 TI - Non-incineration microwave assisted sterilization of medical waste. AB - A non-incineration method for sterilizing hospital infectious wastes has been studied and realized. A small apparatus operating at 2.45 GHz and at a power of 3 kW was designed to optimize power transfer from the electromagnetic field to the infectious materials, which have been previously shredded and moisture-corrected. The high pressure reached in the reactor, 7 atm, was enough to ensure complete sterilization in just a few minutes for a batch of several hundred grams of waste. Sterilization efficacy during microwave irradiation was also optimized with a new procedure using thermal, microbiological and water vapour sensors in a single test. PMID- 17847677 TI - Techno-economic considerations in the commercial microwave processing of mineral ores. AB - Microwave heating of mineral ores had previously been shown to result in process benefits such as reduced strength and improved mineral liberation, but the economics of the process were not attractive and no attention was given to feasible scale-up. This paper provides an overview of the multi-disciplinary approach that has been required to address these failings and develop the technology to pilot scale. Thermal stress simulations show that the operation at high power densities and short residence times is the optimal operating strategy. Experiments using high power densities (approximately 10(9) W/m3 absorbing phase) and short residence times (approximately 0.1 s) were used to confirm that the benefits can now be achieved at economically viable microwave energy inputs (approximately 1 kWh/t). In order to design applicators, reliable measurement of effective microwave properties of crushed ores is required. A method has been developed to extract dielectric properties when the sample thickness is a multiple of half a guide wavelength at some point in the measurement band. Finite difference time domain modeling has been used to design and simulate applicators. A transverse E field applicator with a reflection compensating step has been developed, and a unit with a capacity of > 10 tons/h is being tested. Preliminary economic analysis shows that the overall cost of the process will be between US $0.16 - 0.85 per ton of ore. PMID- 17847676 TI - Use of fillers to enable the microwave processing of polyethylene. AB - Microwave heating has a number of advantages over conventional heating due to the ability to heat specimens directly through specific interaction of electromagnetic radiation with the material. Thus it is possible to consider highly localised, rapid melting of thermoplastics using microwave radiation as a means of forming and welding. However, most polymers exhibit very low dielectric losses in the GHz region, which means that it is difficult to heat them efficiently by this means. We have therefore studied the use of fillers such as talc, zinc oxide and carbon black as a way of increasing the susceptibility of common polymers to microwave processing. Carbon black was found to be the most effective susceptor for high density polyethylene and its efficiency was directly proportional to its surface area and loading. PMID- 17847678 TI - Study of a microwave assisted vacuum drying process applied to the granulated pharmaceutical drug hydrochlorthiazide. AB - Drying processes have evolved considerably over the years, aiming at the best conditions to shorten the processing time, but maintaining the highest final product quality. The application of vacuums to the microwave drying process might be interesting, especially for thermally sensitive products because the reduced boiling point of the solvent allows a lower temperature processing. The objective of the present work is to study and evaluate the process of drying a granulated product that is the basis of the drug hydrochlorthiazide, with an initial moisture content of 21% in dry basis. This study monitored the drying kinetics, product temperature and power absorbed by the sample using a bench scale vacuum microwave dryer. The equipment consisted of a cylindrical pressure vessel crossed by a wave guide, setting up a system whereby the vacuum pressure, the sample weight and the incident, reflected and residual microwave powers could be measured and evaluated, throughout the entire process. The experimental runs were established with an approximate incident microwave power at 20 W for absolute pressure levels of 50 and 75 mbar, working with samples of about 1.4 g. It was observed that the vacuum microwave process kinetics at both pressure levels showed little difference. The processes were carried out almost entirely in a regime of water evaporation, the product's temperature remaining below the solvent boiling temperature. The drying times were similar for both processes, whereas the absorbed power was slightly higher at the pressure of 75 mbar. PMID- 17847679 TI - An investigation on the effect of varying the load, mesh and simulation parameters in microwave heating applications. AB - The paper attempts to provide a generic proposal on the influence of various microwave load parameters based on results accumulated during an investigation using a specific microwave multimode heating cavity configuration. The results have been obtained by numerical analysis using the Finite Element Method within a 3-D environment. The load parameters considered were dielectric constant, loss factor, load thickness and load position. Load material properties are typical of those used in industrial relevant applications. Of the four load parameters investigated, the configuration with a high loss factor was seen to dominate the load impact regardless of load thickness, load position or dielectric constant. With decreasing loss factor or increasing load thickness, the influence of the dielectric constant increases. Minor adjustments in the load position (10%) is generally seen to have minimal impact for all load properties considered. The paper also investigates the numerical impact of varying load properties. As the dielectric constant increases, which requires a higher number of mesh elements, so does the average iterations per numerical cycle. The number of numerical cycles and time to reach a convergence is also seen to be inversely proportional to the load loss factor. PMID- 17847680 TI - The consultants' contract: is it value for money? PMID- 17847681 TI - How to improve the selection process of surgical trainees. PMID- 17847682 TI - Management of acute urinary retention. PMID- 17847683 TI - Urogynaecology: an ambulatory approach. AB - An ambulatory approach in urogynaecology offers advantages to both patients and providers, offering significant savings on service delivery. This review provides an analysis of and information on procedures available for the ambulatory setup. PMID- 17847684 TI - Haematuria 1: risk factors, clinical evaluation and laboratory investigations. AB - Haematuria is a common complaint presenting to doctors in both community and acute centres. It can be a sign of underlying urinary tract malignancy. Appropriate investigation and management should follow evidence-based practice and recognized guidelines, and subsequently lead to a rapid diagnosis. PMID- 17847685 TI - Metastatic endophthalmitis. AB - Endophthalmitis carries a poor visual prognosis for patients and can be a potentially blinding condition that may result in loss of the eye. Early diagnosis and prompt treatment are imperative to save the eye. Delay in diagnosis affects visual prognosis and therefore doctors should be aware of the presenting features of endophthalmitis. Urgent ophthalmic referral is advised as soon as a diagnosis is suspected. PMID- 17847686 TI - Common rashes in children: 1. PMID- 17847687 TI - Comprehensive geriatric assessment. PMID- 17847688 TI - The applied anatomy of rectal examination. PMID- 17847689 TI - Soft tissue knee injuries. PMID- 17847690 TI - Surgical instruments, sutures and suturing techniques. PMID- 17847691 TI - Dealing with bullying: a guide for the foundation year doctor. PMID- 17847692 TI - Colonoscopic perforation. AB - Perforation is an uncommon but important complication of colonoscopy. This review looks at the incidence, clinical features, diagnosis and treatment of this condition. PMID- 17847693 TI - The radiological investigation of subarachnoid haemorrhage. AB - Subarachnoid haemorrhage is an important condition with a high mortality, so prompt diagnosis is essential. This article will review the investigation of subarachnoid haemorrhage with a radiological bias. Appropriate clinical correlation will be included and it will look at some of the more interesting areas in the investigation of this condition. PMID- 17847694 TI - Inversion of Meckel's diverticulum causing gastrointestinal bleeding and small bowel obstruction. PMID- 17847696 TI - Hypoalbuminaemia and colonic polyps: a case of protein-losing enteropathy with cap polyposis? PMID- 17847697 TI - Crohn's disease discovered by an obstructing chick pea. PMID- 17847698 TI - Squamous cell carcinoma arising in an epidermoid cyst. PMID- 17847699 TI - James Blundell, pioneer of blood transfusion. PMID- 17847700 TI - Hyperprolactinaemia in a patient with cystic fibrosis. PMID- 17847701 TI - The need for income protection. PMID- 17847702 TI - Should non-steroidal anti-inflammatory drugs be given to orthopaedic patients with fractures? PMID- 17847703 TI - Inhibition of Stenotrophomonas maltophilia dihydrofolate reductase by methotrexate: a single slow-binding process. AB - Although antifolates such as trimethoprim are used in the clinical treatment of Stenotrophomonas maltophilia infection, the dihydrofolate reductase (DHFR) of this microorganism is scarcely known because it has never been isolated. Here, we describe the purification of this enzyme and kinetically characterize its inhibition by methotrexate (MTX). Upon MTX treatment, time-dependent, slow binding inhibition was observed due to the generation of a long-lived, slowly dissociating enzyme-NADPH-inhibitor complex. Kinetic analysis revealed a one-step inhibition mechanism (K(I) = 28.9 +/- 1.9 pM) with an association rate constant (k(i)) of 3.8 x 10(7) M(-1)s(-1). Possible mechanisms for MTX binding to S. maltophilia DHFR are discussed. PMID- 17847704 TI - Effect of tetrahydropteridines on the monophenolase and diphenolase activities of tyrosinase. AB - This study explains the action of compounds such as 6-tetrahydrobiopterin, (6BH4) and 6,7-dimethyltetrahydrobiopterin (6,7-di-CH3BH4) on the monophenolase and diphenolase activities of tyrosinase. These reductants basically act by reducing the o-quinones, the reaction products, to o-diphenol. In the case of the diphenolase activity a lag period is observed until the reductant is depleted; then the system reaches the steady-state. In the action of the enzyme on monophenol substrates, when the reductant concentration is less than that of the o-diphenol necessary for the steady-state to be reached, the system undergoes an apparent activation since, in this way, the necessary concentration of o-diphenol will be reached more rapidly. However, when the reductant concentration is greater than that of the o-diphenol necessary for the steady-state to be reached, the lag period lengthens and is followed by a burst, by means of which the excess o-diphenol is consumed, the steady-state thus taking longer to be reached. Moreover, in the present kinetic study, we show that tyrosinase is not inhibited by an excess of monophenol, although, to confirm this, the system must be allowed to pass from the transition state and enter the steady-state, which is attained when a given amount of o-diphenol has accumulated in the medium. PMID- 17847705 TI - Kinetic, thermodynamic and statistical studies on the inhibition of adenosine deaminase by aspirin and diclofenac. AB - The kinetic and thermodynamic effects of aspirin and diclofenac on the activity of adenosine deaminase (ADA) were studied in 50 mM phosphate buffer pH = 7.5 at 27 and 37 degrees C, using UV-Vis spectrophotometry and isothermal titration calorimetry (ITC). Aspirin exhibits competitive inhibition at 27 and 37 degrees C and the inhibition constants are 42.8 and 96.8 microM respectively, using spectrophotometry. Diclofenac shows competitive behavior at 27 degrees C and uncompetitive at 37 degrees C with inhibition constants of 56.4 and 30.0 microM, at respectively. The binding constant and enthalpy of binding, at 27 degrees C are 45 microM, - 64.5 kJ/mol and 61 microM, - 34.5 kJ/mol for aspirin and diclofenac. Thermodynamic data revealed that the binding process for these ADA inhibitors is enthalpy driven. QSAR studies by principal component analysis implemented in SPSS show that the large, polar, planar, and aromatic nucleoside and small, aromatic and polar non-nucleoside molecules have lower inhibition constants. PMID- 17847706 TI - Inhibition and protection of cholinesterases by methanol and ethanol. AB - The cholinesterases have been investigated in terms of the effects of methanol and ethanol on substrate and carbamate turnover, and on their phosphorylation. It was found: 1) that at low substrate concentrations the two alcohols inhibit all three tested cholinesterases and that the optimum activities are shifted towards higher substrate concentrations, but with a weak effect on horse butyrylcholinesterase; 2) that methanol slows down carbamoylation by eserine and does not influence decarbamoylation of vertebrate and insect acetylcholinesterase and 3) that ethanol decreases the rate of phosphorylation of vertebrate acetylcholinesterase by DFP. Our results are in line with the so-called 'approach and-exit' hypothesis. By hindering the approach of substrate and the exit of products, methanol and ethanol decrease cholinesterase activity at low substrate concentrations and allow for the substrate inhibition only at higher substrate concentrations. Both effects appears to be a consequence of the lower ability of substrate to substitute alcohol rather than water. It also seems that during substrate turnover in the presence of alcohol the transacetylation is negligible. PMID- 17847707 TI - Acetylcholinesterases--the structural similarities and differences. AB - Acetylcholinesterase (AChE) is a widely spread enzyme playing a very important role in nerve signal transmission. As AChE controls key processes, its inhibition leads to the very fast death of an organism, including humans. However, when this feature is to be used for killing of unwanted organisms (i.e. mosquitoes), one is faced with the question - how much do AChEs differ between species and what are the differences? Here, a theoretical point of view was utilized to identify the structural basis for such differences. The various primary and tertiary alignments show that AChEs are very evolutionary conserved enzymes and this fact could lead to difficulties, for example, in the search for inhibitors specific for a particular species. PMID- 17847708 TI - Synthesis of a novel series of non-symmetrical bispyridinium compounds bearing a xylene linker and evaluation of their reactivation activity against tabun and paraoxon-inhibited acetylcholinesterase. AB - Nine potential non-symmetrical xylene-bridged AChE reactivators were synthesized using modifications of currently known synthetic pathways. Their potency to reactivate AChE inhibited by the nerve agent tabun and the insecticide paraoxon together with nine symmetrical xylene-bridged compounds, was tested in vitro. Seven compounds were promising against paraoxon-inhibited AChE. Two compounds were found to be more potent against tabun-inhibited AChE than obidoxime at a concentration applicable in vivo. PMID- 17847709 TI - Mechanism and inhibitory effect of galangin and its flavonoid mixture from Alpinia officinarum on mushroom tyrosinase and B16 murine melanoma cells. AB - The whitening effects of the flavonoid constituents of Alpinia officinarum Hance were investigated on melanin biosynthesis in B 16 mouse melanoma cells, tyrosinase inhibition and UV absorption. The melanin content was reduced to 1.276 microg /10(5) cell for flavonoid mixture and 1.161 microg /10(5) cell for galangin while the melanin control was 1.632 microg/10(5) cell. Both flavonoid mixture and galangin reduced melanin production with an inhibition of 21.81% and 28.86% at a concentration of 26.5 microg/mL and 29 microg/mL (107.4 microM), respectively. Tyrosinase inhibition by the flavonoid mixture and galangin were higher at lower concentrations and galangin showed competitive inhibition at a concentration less than 21.23 microg/mL which was soluble. In addition, the flavonoid mixture and galangin showed a broad absorption band at 270 approximately 290 nm related to the UV-B area. These observations suggest that galangin may be a whitening agent and a promising candidate for prevention of skin cancer. This is the first full scale report on the evaluation of the whitening effect of galangin. PMID- 17847710 TI - Phosphoprotein levels, MAPK activities and NFkappaB expression are affected by fisetin. AB - Flavonoids, polyphenolic phytochemicals, are ubiquitous in plants and are commonly present in the human diet. They may exert diverse beneficial effects, including antioxidant and anticarcinogenic activities. The present study was designed to evaluate three biomolecules that play important roles in the apoptotic process: mitogen-activated protein kinases, protein phosphatases and NFkappaB, using HL60 cells treated with fisetin as an experimental model. Our results demonstrated that cells treated with fisetin presented high expression of NFkappaB, activation of MAPK p38 and an increase of phosphoprotein levels; inhibition of enzymes involved in redox status maintenance were also observed. Our findings reinforce the hypothesis that fisetin is likely to exert beneficial and/or toxic actions on cells not through its potential as antioxidant but rather through its modulation of protein kinase and phosphatase signaling cascades. Additionally, our results also indicate that the cellular effects of fisetin will ultimately depend on the cell type and on the extent to which they associate with the cells, either by interactions at the membrane or by uptake into the cytosol. PMID- 17847711 TI - Inhibitory effects of diesel exhaust components and flavonoids on 20alpha hydroxysteroid dehydrogenase activity in mouse tissues. AB - The inhibitory effects of diesel exhaust components and flavonoids on 20alpha hydroxysteroid dehydrogenase (20alpha-HSD) activity were examined in cytosolic fractions from the liver, kidney and lung of male mice. 9,10-Phenanthrenequinone (9,10-PQ) and 1,2-naphthoquinone (1,2-NQ), which are contained in diesel exhaust particles (DEPs), potently inhibited 20alpha-HSD activity in liver cytosol. 9,10 PQ also inhibited the enzyme activity in lung cytosol. However, 20alpha-HSD activity in kidney cytosol was little inhibited by 9,10-PQ or 1,2-NQ. Flavonoids such as quercetin, fisetin and kaempferol exhibited high inhibitory potencies for 20alpha-HSD activity in liver cytosol, whereas these flavonoids were poor inhibitors for the enzyme activity in kidney cytosol. It is likely that several diesel exhaust components and flavonoids augment the signaling of progesterone in the liver cells, by potently inhibiting 20alpha-HSD activity in mouse liver cytosol. The possibility that there are distinct enzymes catalyzing 20alpha-HSD activity in the non-reproductive tissues of male mice is also discussed. PMID- 17847712 TI - N-acyl-3,5-bis(arylidene)-4-piperidones and related compounds which stimulate fyn kinase. AB - This study is part of a long term project designed to explore the hypothesis that stimulation of cancer cells followed by treatment with one or more cytotoxic agents may create greater damage to tumours than to the corresponding normal tissues. The aim of the present investigation was to discover various compounds which stimulate a protein tyrosine kinase, namely fyn kinase. The N-acyl-3,5 bis(arylidene)-4-piperidones and related analogues activated this enzyme using concentrations of 25 microM while representative molecules achieved this result at 0.1 microM. Molecular modelling suggested that the compounds interact transiently with the ATP binding site of fyn kinase thereby enhancing the catalytic phosphorylation of proteins. In the future, candidate antineoplastic agents will be designed which incorporate the structural features of these enzyme stimulators with the goal of their being formed in vitro and in vivo prior to the release of cytotoxins. PMID- 17847713 TI - Synthesis and evaluation of novel N-H and N-substituted indole-2- and 3 carboxamide derivatives as antioxidants agents. AB - We have previously reported on the synthesis of novel indole derivatives where some compounds showed significant antioxidant activity. Here, we report the synthesis of novel N-H and N-substituted indole-2- and 3-carboxamide derivatives and investigated their antioxidant role in order to identify structural characteristics responsible for activity. Although all compounds showed a strong inhibitory (95-100%) effect on superoxide anion (SOD) only compounds 4, 5 and 6 showed simliar potency for the inhibition of lipid peroxidation (81-94%) which revealed that compounds 4, 5 and 6 possessed highly potent antioxidant properties. Substitution in the 1-position of the indole ring caused the significant differences between the activity results regarding lipid peroxidation inhibition. PMID- 17847714 TI - Aryl acylamidase activity of human serum albumin with o-nitrotrifluoroacetanilide as the substrate. AB - Albumin is generally regarded as an inert protein with no enzyme activity. However, albumin has esterase activity as well as aryl acylamidase activity. A new acetanilide substrate, o-nitrotrifluoroacetanilide (o-NTFNAC), which is more reactive than the classical o-nitroacetanilide, made it possible to determine the catalytic parameters for hydrolysis by fatty-acid free human serum albumin. Owing to the low enzymatic activity of albumin, kinetic studies were performed at high albumin concentration (0.075 mM). The albumin behavior with this substrate was Michaelis-Menten like. Kinetic analysis was performed according to the formalism used for catalysis at high enzyme concentration. This approach provided values for the turnover and dissociation constant of the albumin-substrate complex: k(cat) = 0.13 +/- 0.02 min(-1) and Ks = 0.67 +/- 0.04 mM. MALDI-TOF experiments showed that unlike the ester substrate p-nitrophenyl acetate, o-NTFNAC does not form a stable adduct (acetylated enzyme). Kinetic analysis and MALDI-TOF experiments demonstrated that hydrolysis of o-NTFNAC by albumin is fully rate limited by the acylation step (k(cat) = k2). Though the aryl acylamidase activity of albumin is low (k(cat)/Ks = 195 M(-1)min(-1)), because of its high concentration in human plasma (0.6-1 mM), albumin may participate in hydrolysis of aryl acylamides through second-order kinetics. This suggests that albumin may have a role in the metabolism of endogenous and exogenous aromatic amides, including drugs and xenobiotics. PMID- 17847715 TI - Xanthine oxidase catalyzes the oxidation of retinol. AB - In mammals, xanthine oxidase (E.C. 1.17.3.2) catalyzes the hydroxylation of a wide variety of heterocyclic substrates such as purines, pyrimidines, and pterins, in addition to aldehydes [1] as all-trans-retinaldehyde [2-5]. Here, we show that buttermilk xanthine oxidase was capable to oxidizing all-trans-retinol (t-ROL) to all-trans-retinaldehyde (t-RAL) that was successively oxidized to all trans-retinoic acid (t-RA). A rise in the enzyme activity, when t-ROL-CRBP complex was assayed, with respect to the free t-ROL, was observed. Furthermore, treatment of the enzyme with Na2S and glutathione resulted in a significant increment in catalytic activity toward t-ROL and t-RAL, due to the reconstitution of the native structural organization of the molybdenum centre of molybdopterin cofactor of the desulfo form of xanthine oxidase. PMID- 17847716 TI - Synthesis, spectroscopic and biological aspects of iron(II) complexes. AB - Five novel coordinated complexes of iron(II) with ciprofloxacin and neutral bidentate ligands have been prepared and characterized using elemental analyses, magnetic measurements, IR spectra, UV-VIS spectral, thermogravimetric analyses, 1H-NMR and 13C-NMR. The antimicrobial activity of the individual ligands, metal salt and metal complexes with respect to Bacillus subtilis, Escherichia coli, Bacillus cereus, Staphylococcus aureus, Salmonella typhi, Serratia marcescens, Aspergillus niger, Aspergillus flavus and Lasiodiplodia theobromae were evaluated by the agar-plate technique in comparison to reference standard drugs (ofloxacin, levofloxacin and fluconozole). Binding of the complexes to DNA was studied and is discussed. PMID- 17847717 TI - The inhibition kinetics of yeast glutathione reductase by some metal ions. AB - Glutathione reductase (GR, type IV, Baker's yeast, E.C 1.6.4.2) is a flavoprotein that catalyzes the NADPH-dependent reduction of oxidized glutathione (GSSG) to reduced glutathione (GSH). In this study some metal ions have been tested on GR; lithium, manganese, molybdate, aluminium, barium, zinc, calcium, cadmium and nickel. Cadmium, nickel and calcium showed a good to moderate inhibitory effect on yeast GR. GR is inhibited non-competitively by Zn2+ (up to 2 mM) and activated above this concentration. Ca2+ inhibition was non-competitive with respect to GSSG and uncompetitive with respect to NADPH. Nickel inhibition was competitive with respect to GSSG and uncompetitive with respect to NADPH. The inhibition constants for these metals on GR were determined. The chelating agent EDTA recovered 90% of the GR activity inhibited by these metals. PMID- 17847718 TI - New antifungal flavone glycoside from Butea monosperma O. Kuntze. AB - A new bioactive flavone glycoside was isolated from the methanol soluble fraction of the flowers of Butea monosperma O. Kuntze, which was identified as 5,7 dihydroxy-3,6,4'-trimethoxyflavone-7-O-alpha-L-xylopyranosyl-(1-->3)-O-alpha-L arabinopyranosyl-(1-->4)-O-beta-D-galactopyranoside (1) by several colour reactions, chemical degradations and spectral analysis. The compound 1 shows antimicrobial activity against various fungal species. PMID- 17847719 TI - Evaluation of the inhibitory activities of aceraceous plants on fatty acid synthase. AB - Fatty acid synthase (FAS) is a very significant lipogenic enzyme participating in energy metabolism in vivo and has been reported as a potential new therapeutic target for cancer treatment. The extracts from sixteen Aceraceae were prepared to assay their inhibitory activities against duck liver FAS and their correlated antitumor bioactivity. Their inhibition of FAS was composed of a reversible fast binding inhibition, by which 0.41 microg/mL of the A. campestre extract inhibits 50% FAS activity, and an irreversible slow-binding inhibition with inactivation rate constants, k(obs), ranging between 1.5 x 10(-3) and 10.6 x 10(-3) min(-1). Three Aceraceae extracts were selected from their smaller IC50 values to study different type of inhibitions against the three substrates in the FAS overall reaction. As compared with other reported FAS inhibitors including EGCG with regard to inhibition constant and IC50 value, the extracts appeared to be more efficient inhibitors, and exhibited a considerable inhibition against the growth of five types of cancer cells (China patent application number 200610088901.6), which may be related to the inhibition of lipogenesis in these cells. PMID- 17847720 TI - Synthesis of some 4-arylidenamino-4H-1,2,4-triazole-3-thiols and their antituberculosis activity. AB - The increasing clinical importance of drug-resistant mycobacterial pathogens has lent additional urgency to microbiological research and new antimycobacterial compound development. For this purpose, new triazoles were synthesized and evaluated for antituberculosis activity. A series of 4-arylidenamino-4H-1,2,4 triazole-3-thiol derivatives (2a-n) were synthesized from the treatment of 4 amino-4H-1,2,4-triazoles-3-thiol (1) with the respective aldehydes and were evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv (ATCC 27294), using the BACTEC 460 radiometric system and BACTEC 12B medium. Compound 2k showed an intereting activity at 6.25 microg/mL with a 87 percentage inhibition. PMID- 17847721 TI - Measuring edema in irradiated head and neck cancer patients. AB - OBJECTIVES: Edema is a common side effect of radiotherapy for head and neck cancer. Systems have been developed to record and monitor changes that occur after radiotherapy. These lack the sensitivity to record edema in specific laryngo-pharyngeal structures. The aim of this study was to develop a rating scale to measure edema in the larynx and pharynx. METHODS: This was an exploratory study to develop a new measure, with the help of an expert panel, assessing interrater and intrarater reliability. A consensus group developed the rating scale. Eleven structures and 2 spaces were identified as areas sensitive to the development of edema. The terms no, mild, moderate, and severe were used to describe the degrees of edema. The scale was piloted and then tested for interrater and intrarater reliability on 5 speech and language therapists. They viewed 25 nasendolaryngoscopic images (23 patients who had had radiotherapy and 2 healthy volunteers). The images were rated with the scale. This process was repeated 1 week later. RESULTS: Images were taken from patients with oral, oropharyngeal, nasopharyngeal, or laryngeal cancer. All had had radiotherapy or chemoradiotherapy. All raters were experienced in viewing larynges via nasendolaryngoscopy. The interrater reliability for scoring the edema rating scale was moderate (weighted kappa, 0.54). Lower levels of agreement were found for the tongue base, valleculae, pharyngeal walls, and anterior commissure. The intrarater reliability was very good (weighted kappa, 0.84). CONCLUSIONS: The edema rating scale can be scored with very good test-retest reproducibility and moderate levels of agreement between clinicians. Modifications to the method are suggested to increase interrater reliability. PMID- 17847722 TI - Thermal welding versus cold dissection tonsillectomy: a prospective, randomized, single-blind study in adult patients. AB - OBJECTIVES: We performed a single-blind, prospective, randomized, controlled clinical study to compare the rates of postoperative morbidity in adults undergoing thermal welding tonsillectomy versus cold dissection tonsillectomy. METHODS: Thirty-two adults with recurrent tonsillitis who were scheduled for elective tonsillectomy were randomized to either thermal welding or cold dissection tonsillectomy groups. The main outcome measures included intraoperative blood loss, intensity of postoperative pain expressed on a 10-cm visual analog scale (with 0 representing no pain and 10 representing the worst possible pain), day of cessation of significant pain (ie, a pain score of at least 7), and presence of postoperative hemorrhage estimated on a 3-point scale (with 0 representing no bleeding, 1 representing minor bleeding, and 2 representing major bleeding). Additional outcome measures included total analgesic requirements, last day of receipt of analgesics, presence of nausea and/or vomiting, and wound healing after 10 days of surgery. RESULTS: The rate of intraoperative blood loss was significantly lower in the thermal welding group (p < .0001). Patients who had thermal welding tonsillectomy also showed a general trend toward lower pain scores, and this difference was statistically significant from the first to the fourth postoperative days (p < .05). Cessation of significant pain also occurred 3 days earlier in this group (p < .05). No significant difference was observed regarding pain medication, nausea and/or vomiting, postoperative hemorrhage, or wound healing. CONCLUSIONS: Thermal welding tonsillectomy is a relatively safe and reliable method with significantly less postoperative morbidity than cold dissection tonsillectomy. PMID- 17847723 TI - Multilevel esophageal biopsy in children with airway manifestations of extraesophageal reflux disease. AB - OBJECTIVES: Extraesophageal reflux disease (EERD) is a recognized cause of upper airway symptoms in children. Direct microlaryngoscopy and bronchoscopy (MLB) is performed for diagnostic information as to the extent and severity of the inflammation caused by gastric refluxate. Esophagoscopy with multilevel biopsy performed at the time of MLB may provide the clinician with additional information to assist in the management of EERD. We undertook to determine the role of multilevel esophageal biopsy in children who have airway manifestations secondary to EERD. METHODS: We performed a retrospective chart review of 139 esophagoscopies with multilevel biopsy done at the time of MLB by a single provider for evaluation of symptoms highly associated with EERD at a tertiary care children's hospital. The histopathologic presence of esophagitis was analyzed by site and compared to the presence and location of tracheolaryngeal abnormalities. RESULTS: Tracheolaryngeal abnormalities associated with EERD were found in 97% of patients when evaluated by MLB. Concomitant esophagitis was found in 59% of these patients. Of patients who had 0, 1, 2, 3, 4, or 5 positive findings on MLB, 75% (3 of 4), 58% (7 of 12), 57% (20 of 35), 62% (32 of 51), 56% (18 of 32), and 80% (4 of 5), respectively, had at least 1 positive biopsy. CONCLUSIONS: We found that EERD that affects the pediatric upper airway was associated with esophagitis in more than half of the patients. The usefulness of 4-level biopsies during esophagoscopy and concomitant airway endoscopy will be discussed. PMID- 17847724 TI - Value of laryngeal electromyography in diagnosis of vocal fold immobility. AB - OBJECTIVES: We sought to determine the value of laryngeal electromyography (LEMG) and evoked LEMG in the diagnosis of vocal fold immobility. METHODS: We analyzed 110 cases of vocal fold immobility by their clinical manifestations and LEMG characteristics, including spontaneous potential activity, motor unit potential measurement, recruitment pattern analysis, and evoked LEMG signals. RESULTS: With LEMG, we identified 87 patients with neuropathic laryngeal injuries. Neurogenic vocal fold immobility showed a wide variety of abnormal activity. Fibrillation potentials and positive sharp waves were found in patients with laryngeal nerve injuries. For laryngeal paralysis, there was no reaction with LEMG and evoked LEMG. For incomplete laryngeal paralysis, decreased evoked LEMG signals were also seen with delayed latency (thyroarytenoid muscle, 2.2 +/- 1.0 ms, p < .01; posterior cricoarytenoid muscle, 2.4 +/- 1.0 ms, p < .05) and lower amplitude (thyroarytenoid muscle, 0.9 +/- 0.7 mV, p < .05; posterior cricoarytenoid muscle, 1.2 +/- 1.0 mV, p < .01). Nineteen patients with vocal fold mechanical limitations generally had normal LEMG and evoked LEMG signals. Four patients with neoplastic infiltration of the laryngeal muscles demonstrated abnormal LEMG signals but nearly normal evoked LEMG signals. CONCLUSIONS: We conclude that LEMG and evoked LEMG behavior plays a crucial role in the diagnosis of vocal fold immobility. The decreased recruitment activities on LEMG and the decreased evoked LEMG signals with longer latency and lower amplitude reflect the severity of neuropathic laryngeal injury. PMID- 17847725 TI - Intraobserver and interobserver reliability in laryngopharyngeal sensory discrimination thresholds: a pilot study. AB - OBJECTIVES: Laryngopharyngeal sensory discrimination threshold (LPSDT) testing is a method used to detect sensory deficits in patients in whom swallowing disorders are suspected. LPSDTs have been used to stratify patient risk status with regard to aspiration and to guide dietary management. The aim of this pilot study was to evaluate the intraobserver and interobserver reliability of LPSDT testing among a group of examiners with differing levels of testing experience. METHODS: Twenty seven healthy volunteers were enrolled in the study to elicit LPSDTs for intraobserver and interobserver reliability measurements. The examiners represented 3 levels of testing experience: an attending laryngologist, a laryngology fellow, and an otolaryngology resident. With the examiners blinded to test results, each subject was examined twice by one examiner and once by a different examiner in an alternating fashion. RESULTS: Six subjects were unable to tolerate the examinations because of coughing and gagging. Spearman rank correlations revealed strong intraobserver reliability for the experienced endoscopists (ie, attending and fellow) but poor reliability for the novice endoscopist (ie, resident). Poor interobserver reliability regardless of endoscopy experience was found. Eighteen percent of the participants demonstrated LPSDTs of more than 4.0 mm Hg (above normal). CONCLUSIONS: 1) Intraobserver reliability was good for experienced endoscopists. 2) Interobserver LPSDT agreement between endoscopists was poor. 3) Eighteen percent of the subjects demonstrated elevated LPSDT thresholds of more than 4 mm Hg. PMID- 17847726 TI - Tonsillectomy in the anticoagulated patient. AB - OBJECTIVES: The objectives of this study were to review perioperative bridging strategies for anticoagulated patients and to describe a novel bridging strategy for tonsillectomy in an anticoagulated patient that addresses both primary and secondary hemorrhage risks. METHODS: A literature review and a case report are presented. PubMed was reviewed for evidence-based recommendations on perioperative management of anticoagulated patients. A case report is detailed of a 28-year-old woman with antiphospholipid syndrome on warfarin for high risk of venous thrombosis who underwent tonsillectomy. A perioperative bridging strategy incorporating outpatient low-molecular weight heparin and inpatient unfractionated heparin was implemented to minimize risks of thrombosis and primary and secondary posttonsillectomy hemorrhage. RESULTS: Limited evidence supports a consensus on the best perioperative management of anticoagulated patients. Tonsillectomy in an anticoagulated patient has not been described previously. The patient in this case underwent successful tonsillectomy with no thrombosis or bleeding after 1 month of follow-up. CONCLUSIONS: Tonsillectomy can be done relatively safely in an anticoagulated patient at high risk for thrombosis. The perioperative bridging strategy should account for its unique risk of primary and secondary postoperative hemorrhage. A proposed algorithm for managing these competing risks is presented. PMID- 17847727 TI - Successful treatment of autophonia with botulinum toxin: case report. AB - OBJECTIVES: We sought to treat autophonia due to a patulous eustachian tube using botulinum toxin. METHODS: Because we assumed that the patulous eustachian tube was caused by abnormal activity of paratubal muscles (tensor and levator veli palatini muscles and salpingopharyngeus muscle), paralysis was performed via injection of botulinum toxin type A in a 45-year-old female professional musician who had had chronic unilateral autophonia for 20 years. In addition to a patient interview, an endoscopic examination of the nasopharynx (posterior rhinoscopy), ear microscopy, and impedance audiometry were performed to verify the diagnosis and the outcome after treatment. RESULTS: The autophonia disappeared 1 week after treatment. Normalized tympanic ventilation was verified by impedance audiometry after 8 weeks. The period of symptom relief was 9 months. CONCLUSIONS: The administration of botulinum toxin type A provides a new option in the treatment of patulous eustachian tube. The reliability of this method and the effect of repeated injections remains to be proved in future studies. PMID- 17847728 TI - Expression of neutrophil gelatinase-associated lipocalin in human salivary glands. AB - OBJECTIVES: We performed an observational study of RNA and protein expression in human tissue to examine the distribution of neutrophil gelatinase-associated lipocalin (NGAL) in normal and chronic inflammatory salivary tissues, and to investigate the expression level of NGAL in inflammatory conditions of salivary glands. METHODS: Normal salivary gland tissues and tissue samples of salivary glands with chronic sialadenitis were obtained. Expression of NGAL was investigated by reverse transcriptase-polymerase chain reaction, and semiquantitative analysis of these results was also performed. The differential localization and amount of immunoreactivity to NGAL protein was evaluated by immunohistochemistry and Western blot analysis in normal salivary gland tissues and salivary glands with chronic sialadenitis. RESULTS: NGAL messenger RNA transcripts were detected in the tissues from the salivary glands with chronic sialadenitis, but only a small amount was detected in the tissues from the normal salivary glands. A weak expression of NGAL protein was occasionally seen in a few ductal epithelial cells of normal salivary gland tissue. However, in tissue samples from glands with chronic sialadenitis, the NGAL protein was expressed strongly in ductal epithelial cells and infiltrating inflammatory cells. CONCLUSIONS: These results imply that NGAL is associated with the regulation of inflammation in salivary glands. PMID- 17847729 TI - Neuromuscular specializations within human pharyngeal constrictor muscles. AB - OBJECTIVES: At present it is believed that the pharyngeal constrictor (PC) muscles are innervated by the vagus (X) nerve and are homogeneous in muscle fiber content. This study tested the hypothesis that adult human PCs are divided into 2 distinct and specialized layers: a slow inner layer (SIL), innervated by the glossopharyngeal (IX) nerve, and a fast outer layer (FOL), innervated by nerve X. METHODS: Eight normal adult human pharynges (16 sides) obtained from autopsies were studied to determine 1) their gross motor innervation by use of Sihler's stain; 2) their terminal axonal branching by use of acetylcholinesterase (AChE) and silver stain; and 3) their myosin heavy chain (MHC) expression in PC muscle fibers by use of immunocytochemical and immunoblotting techniques. In addition, the specialized nature of the 2 PC layers was also studied in developmental (newborn, neonate, and senescent humans), pathological (adult humans with idiopathic Parkinson's disease [IPD]), and comparative (nonhuman primate [adult macaque monkey]) specimens. RESULTS: When nerves IX and X were traced from their cranial roots to their intramuscular termination in Sihler's-stained specimens, it was seen that nerve IX supplied the SIL, whereas branches of nerve X innervated the FOL in the adult human PCs. Use of AChE and silver stain confirmed that nerve IX branches supplying the SIL contained motor axons and innervated motor end plates. In addition to distinct motor innervation, the SIL contained muscle fibers expressing slow-tonic and alpha-cardiac MHC isoforms, whereas the FOL contained muscle fibers expressing developmental MHC isoforms. In contrast, the FOL became obscured in the elderly and in the adult humans with IPD because of an increased proportion of slow muscle fibers. Notably, distinct muscle fiber layers were not found in the human newborn and nonhuman primate (monkey), but were identified in the 2-year-old human. CONCLUSIONS: Human PCs appear to be organized into functional fiber layers, as indicated by distinct motor innervation and specialized muscle fibers. The SIL appears to be a specialized layer unique to normal humans. The presence of the highly specialized slow-tonic and alpha-cardiac MHC isoforms, together with their absence in human newborns and nonhuman primates, suggests that the specialization of the SIL maybe related to speech and respiration. This specialization may reflect the sustained contraction needed in humans to maintain stiffness of the pharyngeal walls during respiration and to shape the walls for speech articulation. In contrast, the FOL is adapted for rapid movement as seen during swallowing. Senescent humans and patients with IPD are known to be susceptible to dysphagia; and this susceptibility may be related to the observed shift in muscle fiber content. PMID- 17847730 TI - Age-related changes in the murine larynx: initial validation of a mouse model. AB - OBJECTIVES: Changes in voice are commonly associated with aging (presbyphonia). Age-related voice change significantly impairs elderly individuals' ability to communicate meaningfully with others and affects their quality of life. With changing age demographics in our society and increasing emphasis on quality of life, treatment of presbylaryngis is becoming more paramount. METHODS: We used 9 aged and 9 young mice to validate a mouse model for the aging larynx. We stained the larynges with Alcian blue to determine the hyaluronic acid content, trichrome stain to determine the collagen content, and immunohistochemical stain for alpha smooth muscle actin to determine the myofibroblast content. Morphometric measurements were performed for muscle area, muscle thickness, and muscle fiber diameter. RESULTS: Statistically significant differences in the density measurements of hyaluronic acid and collagen reflected decreased hyaluronic acid and increased collagen content in the aging larynx. We found alpha smooth muscle actin-labeled myofibroblasts only in the aged larynges. No statistically significant differences were found in the morphometric measurements. CONCLUSIONS: Aged mice may make a practical model for the age-related changes in the vocal folds that can be used further in studies aiming to correct these changes. PMID- 17847731 TI - Nimodipine improves reinnervation and neuromuscular function after injury to the recurrent laryngeal nerve in the rat. AB - OBJECTIVES: Injury of the recurrent laryngeal nerve (RLN) is associated with a high degree of neuronal survival, but leads to various levels of vocal fold motion impairment or laryngeal synkinesis, which has been attributed to misdirected reinnervation of the target muscles in the larynx or aberrant, competing reinnervation from adjacent nerve fibers. The aim of the present study was to evaluate the impact of the regeneration-promoting agent nimodipine on reinnervation and neuromuscular function following RLN crush injury. METHODS: Sixty adult rats were randomized into nimodipine-treated or untreated groups and then underwent RLN crush injury. Reinnervation of the posterior cricoarytenoid muscle (PCA) was assessed by electrophysiological examination, retrograde tracing of lower motor neurons before and after injury, and quantification of neuromuscular junctions in the PCA muscle. RESULTS: At 6 weeks after injury, the nimodipine-treated animals showed significantly enhanced neuromuscular function and also demonstrated a higher number of motor neurons in the brain stem that had reinnervated the PCA, compared to the untreated animals. The somatotopic organization of ambiguus motor neurons innervating the larynx was similar before injury and after reinnervation. CONCLUSIONS: Nimodipine improves regeneration and neuromuscular function following RLN injury in the adult rat, and could be of use in future strategies following RLN injury. PMID- 17847732 TI - Large jugular bulb diverticulum invading the internal auditory canal. AB - OBJECTIVES: We report, with neuro-otologic findings, a very rare case of a large jugular bulb diverticulum eroding the internal auditory canal (IAC). METHODS: We present the imaging and functional studies of a 29-year-old woman in whom a large jugular bulb diverticulum on the left side was found incidentally. RESULTS: Imaging studies revealed a normal external auditory canal, middle ear, and inner ear, but a large jugular bulb diverticulum extending superiorly on the left side had eroded the IAC from below and behind with destruction of the petrous bone. Caloric responses and facial movements were normal. Vestibular evoked myogenic potentials with bone conduction stimuli were absent on the left, indicating dysfunction of the left inferior vestibular system. CONCLUSIONS: This is the first report in the English-language literature of detailed imaging and functional findings in a very large diverticulum invading the IAC. Vestibular evoked myogenic potentials were useful in uncovering subclinical inferior vestibular system dysfunction in the jugular bulb diverticulum invading the IAC. PMID- 17847733 TI - Re: Pediatric otolaryngologists' use of genetic testing. PMID- 17847734 TI - [Chronic prostatitis: critical review of its current nosologic definition, classification and potential carcinogenesis]. AB - Updated critical review of chronic prostatitis as a nosologic, anatomic-clinical entity of supposed microbiological or inflammatory origin. Scientific reasoning about the role of amicrobial inflammation in both caudal and cranial prostate, after new progresses, to reconsider the convenience of maintaining the current classification of chronic prostatitis, mainly in the section referred to "histological prostatitis". Analysis of scientific evidences relating prostatitis and "pelvic pain", the dominant syndrome in many patients and basement of the current terminological proposal: prostatitis-pelvic pain. The role of inflammation in the genesis of BPH and prostate cancer. Justification and convenience of a new term in logic consensus on prostatitis. PMID- 17847735 TI - [Working with urinary incontinence in primary health care: satisfaction, sexuality and therapeutic compliance]. AB - OBJECTIVES: Our aim is not only to measure the satisfaction of both sex patients with urinary incontinence but also to analyse the influence of urgency incontinence in our patient's sexuality as well as their treatment fulfilment. METHODS: This is a quasi-experimental naturalistic, longitudinal, open and not controlled study made during 24 weeks with before-after analysis on 60 urgent or mixed urinary incontinence patients treated with physic therapy and tolterodine. We have used the Spanish version of the questionnaire about overactive bladder (OAB-q), the Spanish version of the King's Health Questionnaire (KHQ) and the Golombok Rust Inventory of Sexual Satisfaction (G.R.I.S.S.) about sexual satisfaction. We have born in mind treatment fulfilment. RESULTS: The 56.25% (18) of the valid calendars showed "normal" mictional values at the end of the study (p < 0.001). Each item of the OAB-q has improved after the treatment of the 26.55% (p < 0.001). The health status has also improved in the KHQ (p < 0.001), but it hasn't happened the same in the G.R.I.S.S. Finally, an improvement in several items of the treatment fulfilment can be contrasted. CONCLUSIONS: The results of this study corroborate the efficiency of pelvic floor rehabilitation combined with pharmacological therapy in urinary incontinence treatment. These results are very hope-giving because the incontinence problem affects negatively to the patients' perception of their own health status, so solving this problem their health status will be improved. PMID- 17847736 TI - [Surgical treatment of urethral stenosis: update]. AB - OBJECTIVES: To compile the main methods of surgical treatment of penile and bulbar urethral stenosis. METHODS: We review the most updated bibliography, focusing on authors with large experience in the treatment of urethral stenosis, and we use our own experience to contrast or reaffirm some of the techniques. RESULTS/CONCLUSIONS: The base of the treatment of urethral stenosis remains in the stenosis itself (localization, etiology and length) and also in patient's characteristics (age, past medical history). Among the techniques of urethroplasty we have techniques in one step, as the technique of excision and anastomosis, and the use of free grafts or vascularized flaps. The techniques in two steps like Johannson's or perineostomy are very useful in certain cases of complex stenosis. We should keep an eye on the development of new techniques and the use of new materials that will help, once consolidated, to improve results. PMID- 17847737 TI - [Radiotherapy after radical prostatectomy: description, outcome and prognostic factors in and emerging practice]. AB - OBJECTIVES: Recently it has been reported in the EORTC (European Organisation for Research and Treatment of Cancer) trial 22911 and the SWOG (Southwest Oncology Group) 8794, the evidence that radiotherapy (RT) is an effective treatment after the prostatectomy in patients with high risk of biochemical failure. We analyze predictor factors of biochemical relapse and the potential benefits induced by rescue treatment are the main purposes of our study. METHODS: From 1993 to 2003, 597 prostatectomy were followed at Hospital Universitario Gregorio Maranon de Madrid, identifying 166 patients (p) (28%) of biochemical failure (defined as PSA > or = 0'5 ng/ml, including post-surgical persistent values). 42 p received RT (78% due to delayed PSA relapse). The median total dose was 66 Gy [60-74]. RESULTS: Clinical variables: Median age: 68 years [49-80], median PSA at diagnosis: 29,8 ng/ml [2,6475]; presurgical Gleason > or = 7: 65%. Histological variables: Prostatectomy induces stage migration to superior T (pT3-T4: 95%) and Gleason categories (> or =7: 81%). 83% of relapsed p had positive margins and 90% had pT3-pT4. OUTCOME VARIABLES: median time to biochemical recurrence was 22,2 months. Median time interval between biochemical failure and RT was 10,5 months. Overall survival (5 years) was 86 +/- 6%. Freedom-from-biochemical failure at 5 years was 76 +/- 4%. RT had poor survival in p with PSA > 2 ng/ml pre-RT (p = 0.03), post-prostatectomy persistant disease (p = 0.05) and Gleason score > or = 7 (p = 0.01). No increased grade 3-4 uro-rectal toxicity was observed. CONCLUSIONS: RT after prostatectomy improves freedom-from-biochemical failure in p with PSA values below 2 ng/ml. In our experience, Gleason score > or = 7 is a negative predictor of response. There is no severe toxicity in our series. Improvement of the staging presurgery, the role of the adjuvant androgen deprivation and selection of patients for adjuvant RT focus current studies on treatment after prostatectomy. PMID- 17847738 TI - [Paraurethral ballon implantation in the treatment of male urinary incontinence. La Paz University Hospital experience]. AB - OBJECTIVES: We want to show our experience with paraurethral balloon implantation in the treatment of male urinary incontinence. METHODS: We retrospectively reviewed our series from March 2003 to March 2007, including 69 male patients with urinary incontinence, most of them after radical prostatectomy. RESULTS: 6 patients did not have their first follow-up visit after surgery. Mean follow-up was 22 months (3-48). 57.14% of the patients (36/63 do not need pads, and 12.69% use one safety pad (8/63); therefore 69.83% (44/63) of the patients are dry or use one safety pad. If we stratify patients by incontinence severity, 81.25% of the patients with mild incontinence and 59.25% with moderate incontinence are dry. Nevertheless, only 35% of the patients with severe incontinence are dry (no protection). CONCLUSIONS: In our experience, we believe that paraurethral balloon implantation could be the first therapeutic option for mild and moderate male urinary incontinence. PMID- 17847739 TI - [Urodynamic findings in patients older than 65 years: experience in the Department 19 of the health-care area of Valencia (HCAV)]. AB - OBJECTIVES: This work tries to analyze the urodynamic studies performed in patients over the age of 65 years in the Department 19 of HCAV with the aim of reviewing our activity in this population segment between January 2001 and September 2006, and to perform a clinical-urodynamic correlation which will help to find a diagnosis avoiding the need to repeat urodynamic tests. METHODS: We perform a descriptive transversal study with retrospective analysis of data from patients older than 65 years who underwent urodynamic tests. Total population in this age range in our health-care department (HCD) (HCD 19) is 35.260 inhabitants (12% of total population) (Valencia health care agency. Healthcare Management HCD 19. Alicante General University Hospital. May 2005). In this population 41% are males (14.620 people) and 59% females (20.637 people). RESULTS: Among males, the most frequent urodynamic finding is infravesical obstruction in almost half of the cases (48%), followed by bladder hyperactivity in 197%, and idiopathic bladder hyperactivity and urgency incontinence with 10%, respectively. No reproducibilily of the symptoms reaches 9% of the cases. On the other hand, in females the most frequent finding is mixed urinary incontinence in 25% of the cases, followed by bladder hyperactivity 17%, urgency incontinence 14% and stress urinary incontinence 13%. No reproducibility of the symptoms reached 11%. In the opposite extreme are intravesical obstruction and sphincter/detrusor dyssynergia without any case. CONCLUSIONS: We find that people between 70 and 75 years old are the population group undergoing a greater number of urodynamic tests in our area. The most frequent urodynamic tests performed at our department was pressure/flow study with evaluation of post void residual. Urethra profile was reserved for recurrent stress urinary incontinence after surgery. Obstructive symptoms in males and mixed urinary incontinence in females were the most frequent causes for the indication of urodynamic tests. Our symptom no reproduceability rates were below 10% of the cases. PMID- 17847740 TI - [Clinical experience and results in the treatment of 4402 patients with solitary urinary calculi with the extracorporeal shock wave lithotripter Dornier MFL-500]. AB - OBJECTIVES: To report the series of our Urology Department in the treatment of urinary stone disease with extracorporeal lithotripsy as well as the effectiveness of the Dornier lithotripter MFL-5000. METHODS: 6.602 patients were treated by extracorporeal lithotripsy during 12 years with a total of 17.120 sessions. We examined the treatment outcome of 4.402 patients with a solitary stone, accordingly to stone size and localization. RESULTS: There were no major complications and only 43 patients experienced "calle litiasica". We treated 4.402 stones. For all stones, independently of size and localization, 2615 (59.4%) were treated in one session, 801 (18.2%) required two sessions, 379 (8.6%) 3 sessions, 213 (4.8%) 4 sessions and 373 (8.4%) 5 or more sessions. CONCLUSION: The Dornier MFL-5000 lithotripter successfully treated urinary stone disease in patients of all age groups with a retreatment rate and number of sessions per stone similar to other studies, without analgesia or anesthetic procedures, except in the younger age group. PMID- 17847741 TI - [Subcutaneous endoscopic surgery in urology]. AB - OBJECTIVES: In endoscopic subcutaneous surgical procedures, new to Urology, the subcutaneous tissues are insufflated with carbon dioxide through a trocar to create working space without a surgical incision. Although this technique now predominates in surgery of the face, neck and breast, from the literature it appears that it has not yet been adopted for surgery in the region of the inguinal canal or in the scrotum. We describe these approaches. METHODS: To carry out the inguinal canal approach we introduced three 5mm trocars and dissected the external oblique fascia until we identified the superficial inguinal ring and gained access to the scrotum. The scrotal approach is directly into the scrotum. To date, we have only used the scrotal approach to treat hydroceles. We carefully detached the tunica vaginalis from the scrotal wall and kept the tunica intact before puncturing it to empty the fluid contents. The tunica was then resected and withdrawn through a trocar. RESULTS: We have removed three cysts and one solid tumor of the spermatic cord with the inguinal approach. With the scrotal approach we have treated six hydroceles. Our experience with these two small series allows us to confidently state that the procedure offers no particular technical difficulty; that operating times are short and that post-operative pain is very probably less than usual. CONCLUSIONS: Although endoscopic subcutaneous surgery in Urology is in its infancy, our results until now have been excellent and permit us to conclude that in the future there will be more indications for this type of surgery. PMID- 17847743 TI - [Inverted papilloma. Report of two cases and bibliographic review]. AB - OBJECTIVE: Inverted papilloma is a rare polypoid lesion of the urothelium, known as a different entity since 1963. Not many more than 100 cases have been published. Although its malignant potential is still unknown, several scientific publications have noted it. METHODS: We report to cases of inverted papilloma and perform a detailed bibliographic review. RESULTS: Both patients were diagnosed by the Pathology Department and entered periodic follow-up visits, being free of recurrence at 24 and 18 months respectively. CONCLUSIONS: The possibility that inverted papilloma is a lesion with malignant potential should be considered in every case, and we suggest that patients with this diagnosis should enter a follow-up protocol like any bladder neoplasia. PMID- 17847742 TI - [Laparoscopic nephroureterectomy: new position for the management of distal ureter]. AB - OBJECTIVES: The main challenge of laparoscopic nephroureterectomy is the management of distal ureter, which also will have an important repercussion in the oncological outcome of many cases. We present our experience in such aspect, considering that we performed the last five laparoscopic nephroureterectomies in forced Trendelemburg position, resulting in a more comfortable and safe management of the distal ureter. METHODS: Between August and December 2006 we performed five purely laparoscopic nephroureterectomies with bladder cuff positioning the patient in forced Trendelemburg, a position similar to that of laparoscopic radical cystectomy or prostatectomy. RESULTS: Mean surgical time was 182 minutes (170-210). Mean blood loss was 100 cc and no patient required transfusion. Mean hospital stay was four days. CONCLUSIONS: We believe this position is a good alternative for the management of the distal ureter during the laparoscopic approach. The technique is very similar to open surgery, which continues being the gold standard today. PMID- 17847744 TI - [Bladder leiomyoma. Report of two new cases and bibliographic review]. AB - OBJECTIVE: Primary mesothelial tumors of the bladder are rare entities, being leiomyoma the most frequent of them. It may grow without any clinical symptoms or with very unspecific ones. METHODS: We report two cases of bladder leiomyoma in 2 patients, and performed a bibliographic review. RESULTS: They were treated by transurethral resection, with an excellent outcome, without incidences over five years of follow-up. CONCLUSIONS: Surgical treatment continues to be the best solution; it is easy to perform and has a very limited number of complications. Prognosis is good in any case and progression is anecdotic. PMID- 17847745 TI - [External genitalia lymphedema. Case report]. AB - OBJECTIVES: Penile and scrotal lymphedema produces a monstrous deformity with psychological impact and occasionally extreme mental anguish. The penis is buried in the scrotal tissue, deformed, thickened, edematous, and curved. The scrotum changes to a great, very thick, hard skin mass, sometimes cracked, exudative, and fetid. Erection and sexual intercourse are very difficult or impossible, and the scrotal enlargement interferes with walking. To report a new case of male external genitalia lymphedema. METHODS/RESULTS: We present a technical variation of the surgical treatment of penile-scrotal primary lymphedema in a 32-year-old patient suffering this disease for several years, which had underwent several medical and surgical treatments, such as lymphangioplasty and penile root fasciotomy. Observation consisted in the performance of two incisions in w plasty, one at the root of the penis, the other one in the preserved preputial mucosa, and excision of all the lymphedematous tissue with reconstruction using the preputial mucosa and a small area of non infiltrated skin at the root of the penis. In the scrotum, two butterfly-wing shape skin flaps were performed; the testicles and the spermatic cord were isolated to ease the operation, minimize the surgical time and avoid complications; the lymphedematous tissue was resected with a great fragment of scrotum; finally reconstruction was performed from the adjacent healthy skin. CONCLUSIONS: With this technique it was not necessary to perform a free or vascularized skin graft. The patient recovered his penile functional capacity improved aesthetically and his anguish disappear. PMID- 17847746 TI - [Polypoid cystitis associated with glandular cystic cystitis]. AB - OBJECTIVE: Polypoid cystitis and intestinal metaplasia are well-known lesions of the bladder. METHODS: We report the case of one patient with both lesions identified synchronically in the bladder. RESULTS: Although these lesions are not neoplastic, there are evidences supporting a possible degeneration of the metaplastic epithelium to adenocarcinoma. CONCLUSIONS: The diagnosis of both lesions is histological and there are not clinical tests or image studies that could enable identification of the real nature of these lesions. PMID- 17847747 TI - [Spermatic cord rhabdomyoma]. AB - OBJECTIVE: Rhabdomyomas are benign tumors of the skeletal muscle and extracardiac rhabdomyomas are very rare. METHODS/RESULTS: We report one case of spermatic cord rhabdomyoma in a 28-year-old male. CONCLUSIONS: Genital rhabdomyomas are rare benign tumors. Rhabdomyomas should be considered in the clinicopathological differential diagnosis of tumors of the male genital tract. PMID- 17847748 TI - [Metachronic thyroid metastasis secondary to renal carcinoma. Case report]. AB - OBJECTIVE: We report the case of the patient with metachronic thyroid metastasis of a renal adenocarcinoma. METHODS: 61-year-old patient with the diagnosis of renal adenocarcinoma treated by radical nephrectomy (stage pT3bpN0M0) and subsequent interleukin-2 for twelve months presenting four years after surgery with a thyroid nodule displacing the trachea laterally, requiring left hemithyroidectomy. RESULTS: Pathology reported a lesion made of clear cytoplasm tumor cells, with marked atypia and anaplastic areas, compatible with clear cell renal adenocarcinoma. CONCLUSIONS: Thyroid metastases are extremely rare, being renal tumors the most frequent origin. They present as painless nodules, cold in gammagram, with normal thyroid hormones. The treatment of choice is surgical excision, with a better prognosis the longer the time between the primary and the appearance of metastasis. PMID- 17847749 TI - [Adenomatoid tumor of the epididymis. Report of two cases]. AB - OBJECTIVE: Tumors of the epididymis are rare. They are unusually benign and adenomatoid tumors are the most frequent. Report of two cases of this kind of tumor of the epididymis. METHODS/RESULTS: We report two cases of adenomatoid tumor of the epididymis diagnosed at our hospital during last year. Two males, 35 and 54 years old respectively asked for urology consultation about a palpable scrotal mass. They didn't have any other symptoms. Imaging techniques revealed a solid epididymal mass. Epididymectomy was performed. Pathological diagnosis was adenomatoid tumor. CONCLUSIONS: The majority of epididymal tumors follow a benign course. In the finding of an epididymal mass, after palpation and imaging tests, organ sparing surgery (epididymectomy) is recommended. We will avoid unnecessary orchiectomies. PMID- 17847750 TI - [Mesenteric desmoid tumor mimicking a testicular cancer recurrence]. AB - OBJECTIVE: Report of one case of desmoid tumor in a patient who had been treated of a testicular seminoma 26 months before, with excision of a retroperitoneal mass and chemotherapy. On followup he presented with a mesenteric abdominal mass which was clinically labeleled as a recurrence of the seminoma. RESULTS: Histologically it was reported as a mesenteric desmoid tumor. Differential diagnosis with gastrointestinal stromal tumor was performed with immunohistochemical studies. CONCLUSIONS: Desmoid tumor is rare. There are few cases reported in patients with history of previous testicular tumor. It should be included in the differential diagnosis of testicular tumor recurrences. PMID- 17847751 TI - [Pelvic mass and bilateral anorchia]. PMID- 17847752 TI - [Penile squamous cell carcinoma]. PMID- 17847753 TI - Extragonadal retroperitoneal germ cell tumor: primary versus metastases? AB - OBJECTIVE: Primary extragonadal germ cell tumors are rare and their histogenetic origin is not clear. We describe two cases presenting as primary retroperitoneal germ cell tumors without clinical evidence of testicular tumor. METHODS: A 21 and 18 years-old patients presented retroperitoneal choriocarcinoma and yolk sac tumor, respectively. In both cases, testicular palpation was not suspicious for testicular cancer. Testicular ultrasound founded alterations in right testes. RESULTS: A right orchitectomy were performed and the final diagnostics were mature teratoma associated with intratubular malignant germ cell. CONCLUSION: Adult mature teratoma is infrequent and the retroperitoneal germ cell tumors should be considered to be metastases of a viable or burned-out testicular cancer. PMID- 17847754 TI - Cell growth effects of leuprolide on cultured endometrioma cells. AB - OBJECTIVE: To examine the effect of the GnRH agonist leuprolide on the growth of cultured endometrioma cells. STUDY DESIGN: Experimental study in an academic setting on endometrioma cell lines cultured from 15 women undergoing laparoscopy or laparotomy for excision of endometrioma. RESULTS: Mean cell counts resulting from treatment with lower concentrations were not significantly different from those of the controls. Increasing concentrations of leuprolide resulted in inhibition of cell growth. The inhibitory effect of leuprolide was statistically significant when the 1,000 ng/mL concentration was compared with the control concentration. CONCLUSION: Increased concentrations of leuprolide has suppressive effects on the growth of cultured endometrioma cells. This suggests a direct effect of GnRH agonists acting via GnRH agonist receptors. Long-acting gonadotropin-releasing hormone (GnRH) agonists cause pituitary receptor down regulation and ovarian suppression, a function that has made this class of agents useful for the treatment of endometriosis. Recent work has also revealed that this class of agents may also have a direct suppressive effect on peripheral target tissue, mediated by GnRH and GnRH agonist receptors. Preliminary work has suggested that there are GnRH receptors in endometriotic cells and that the growth of these cells is inhibited by GnRH agonists. This activity, however, has not been extensively studied in the growth of endometrioma cells. The present study evaluated the effect of the GnRH agonist leuprolide on 15 endometrioma cell lines. PMID- 17847755 TI - Comparison of obstetric outcomes in recipients of donor oocytes vs. women of advanced maternal age with autologous oocytes. AB - OBJECTIVE: To evaluate obstetric complications in women conceiving with donated oocytes as compared to controls of advanced maternal age. STUDY DESIGN: We compared the obstetric outcomes of a cohort of 69 women who conceived through oocyte donation to all women over 38 years old (n = 681) who delivered at the same hospital in the same period. We first compared obstetric complications and outcomes in the entire cohort. Additional comparisons were made while controlling for multiple covariates: maternal and fetal complications, mode of delivery, estimated gestational age and infant weight at delivery. RESULTS: Women who conceived with donor oocytes were older than controls. In the cohort, oocyte recipients were at increased risk for several obstetric complications. However, when controlling for age and multiple gestations, only preterm labor, preeclampsia and protracted labor were increased in oocyte recipients. CONCLUSION: Women who conceive with donor oocytes might be at increased risk of complications during pregnancy. When age and multiple gestations are accounted for, these patients remain at risk for preterm labor, preeclampsia and protracted labor requiring cesarean delivery. PMID- 17847756 TI - Laparoscopic uterosacral nerve ablation with and without presacral neurectomy in the treatment of primary dysmenorrhea: a prospective efficacy analysis. AB - OBJECTIVE: To evaluate the efficacy of laparoscopic uterosacral nerve (LUNA) alone vs. LUNA plus presacral neurectomy (PN) in the treatment of primary dysmenorrhea. STUDY DESIGN: Seventy-four patients were randomly allocated to LUNA alone or LUNA plus PN. Evaluation of severity of menstrual pain was based on multidimensional scoring. RESULTS: Sixty-seven patients were eligible for analysis (35 LUNA alone, 32 LUNA plus PN). Baseline demographic features were comparable between the 2 groups. There was no difference between them in the proportion of improvement in dysmenorrhea at 3 months of follow-up (69% for LUNA vs. 73% for LUNA plus PN, p = 0.923), and the results were maintained at 6 and 12 months of follow-up. More surgical complications were found in the LUNA plus PN group. CONCLUSION: For patients with primary dysmenorrhea, LUNA plus PN has no additive therapeutic advantage over LUNA alone, and more surgical complications may be encountered. PMID- 17847757 TI - Surgery combined with muscle therapy for dyspareunia from vulvar vestibulitis: an observational study. AB - OBJECTIVE: To explore the dual importance of treating vestibule allodynia and pelvic floor myalgia in correcting dyspareunia associated with severe vulvar vestibulitis. STUDY DESIGN: In this observational study, 111 women were treated by modified superficial vestibulectomy and were evaluated for referral to physical therapists for pelvic floor myalgia. They were followed with interval repeat examinations. Later cohort assessment was by patient questionnaire surveys. Data from pelvic floor muscle examinations and physical therapy referrals were added by retrospective chart review. Primary outcomes were swab touch sensitivity and dyspareunia. RESULTS: Eighty-five percent of subjects ultimately had nontender vestibule examinations postoperatively. Fewer, numbering 64%, reported resolution of dyspareunia, 24% had less dyspareunia, 9% were no better, and 3% reported they were worse. Fifty percent of those with continued dyspareunia had no remaining vestibulitis, but had tight or tender pelvic muscles. Failure of surgery and physical therapy to correct dyspareunia related significantly to length of symptoms before therapy (p = 0.02). Follow-up averaged 3.7 years, with a range of 0.25-14. CONCLUSION: Superficial surgery can correct vulvar vestibulitis, but without treatment for pelvic floor myalgia, women may continue to have dyspareunia. Physical therapy is an important adjunct to achieve comfort. PMID- 17847758 TI - Pelvic floor function and anatomy after childbirth. AB - OBJECTIVE: To investigate pelvic floor muscle function and anatomy after childbirth in continent women differing in obstetric history. STUDY DESIGN: Young, continent women, age range 20-40 years, were recruited into 3 groups: 1. elective, prelabor cesarean delivery (n =12); 2. vaginal delivery (n = 15); and 3. age-matched nulliparas as controls (n = 13). Pelvic floor muscle strength was measured by a perineometer and also assessed by vaginal palpation. Magnetic resonance imaging of the pelvic floor at rest and on maximal strain was performed. Statistical analysis was carried out using SPSS 10.0 (Chicago, Illinois) for Windows (Microsoft, Redmond, Washington); p < 0.05 was considered significant. RESULTS: Pelvic floor muscle strength was not different between the vaginal delivery and cesarean groups. The descent of the bladder and cervix on straining was greater in the subjects who delivered vaginally than in the cesarean delivery and nulliparous groups. There was a positive and significant correlation between the duration of labor and the area of the levator sling and also between birth weight and the descent of the cervix on straining. CONCLUSION: The results of this study show that delivery method does not affect pelvic muscle strength. PMID- 17847759 TI - Bladder perforation during tension-free vaginal tape surgery: does it matter? AB - OBJECTIVE: To analyze the incidence, possible risk factors, preoperative morbidity and outcome results in tension-free vaginal tape (TVT) cases complicated by lower urinary tract injury in a large, heterogeneous, consecutive group of women. STUDY DESIGN: Four hundred sixty consecutive women who underwent TVT surgery for correction of urodynamically proven stress urinary incontinence were enrolled prospectively. All the procedures were performed at 1 center by 3 experienced surgeons. RESULTS: In this series, 3.9% cases of lower urinary tract injury occurred. Most of the injuries occurred during the learning curve. TVT related urinary tract injury was not associated with increased perioperative morbidity. The cure rates were similar with and without injury. De novo urge and persistent urge incontinence were slightly more common in patients with bladder perforation. CONCLUSION: Lower urinary tract injury during the TVT procedure is directly related to the inexperience of the surgeon. However, TVT-related lower urinary tract injury does not appear to affect medium-term outcome results. PMID- 17847760 TI - Repeated hematocrit measurements in low-risk pregnant women. AB - OBJECTIVE: To determine the incidence of anemia in the third trimester among women with normal hematocrits early in pregnancy. STUDY DESIGN: Low-risk women seeking prenatal care were identified. Patients with a hematocrit >33% in the first or second trimester and a hematocrit drawn in the third trimester were included. Rates of anemia; hematocrit <33%; and severe anemia, hematocrit < 30%; were determined. The primary outcome was the development of anemia in the third trimester. RESULTS: A total of 1,604 women met inclusion criteria; 16.2% of women became anemic, and 4.5% became severely anemic in the third trimester. Using a starting hematocrit value of 39% as a cutoff, only 66% of women would need to be rescreened in the third trimester in order to detect 78.5% of anemias (sensitivity 78.5%, specificity 39.7%, negative predictive value 90.5%). CONCLUSION: The percent of women with normal hematocrits in the first trimester who become anemic in the third trimester is 16.2. Hematocrit screening in the third trimester may be unnecessary for low-risk women with starting hematocrits > 39%. PMID- 17847761 TI - Mechanisms of premature ovarian failure: reappraisal and overview. AB - OBJECTIVE: To present an overview of the potential etiologies of premature ovarian failure (POF), with an emphasis on the chromosomal abnormalities, gene mutations and autoimmune disorders. STUDY DESIGN: This article is based on a literature review of articles on POF using PubMed and MEDLINE for the years 1966 2005 using the keywords premature ovarian failure, trying to ascertain the possible mechanisms of POF reported to date. RESULTS: The etiology of POF is still under investigation, even though a wide range of etiologies has been unveiled, encompassing genetic mutations, chromosomal abnormalities, autoimmune disorders, and iatrogenic (irradiation, chemotherapy) and idiopathic causes. CONCLUSION: In the majority of POF cases, the etiology remains subtle. PMID- 17847762 TI - Incisional endometriomas after Cesarean section: a case series. AB - OBJECTIVE: To review a series of women with endometriomas developing in the scar of the skin incision performed for cesarean section. STUDY DESIGN: A total of 37 patients diagnosed with incisional endometrioma at the time of surgical excision from 1975 to 2005 were identified from the comprehensive surgical database, which includes all operative procedures performed at this institution. The medical records of 33 of the 37 patients were available for review. RESULTS: The endometriomas ranged in size from a diameter of 1-12 cm and were initially observed to be present 6 months to 9 years (mean, 3.2) after the surgical procedure. Diagnosis was best made by needle aspiration of chocolate colored fluid from the mass. Medical therapy with a gonadotropin releasing hormone agonist, medroxyprogesterone acetate or combination oral contraceptives had been attempted in 14 patients without a change in lesion size. All patients were cured by surgical excision of the endometrioma. CONCLUSION: The overall incidence of incisional endometriomas following cesarean section during the 30-year period was 0.08%. Optimal treatment is by surgical excision. It is hypothesized that failure to close the parietal and visceral peritoneum with sutures at the time of cesarean section may markedly increase the postoperative occurrence of an endometrioma in the skin incision scar. PMID- 17847763 TI - IVF patients' attitudes toward multifetal pregnancy reduction. AB - OBJECTIVE: To determine attitudes of in vitro fertilization (IVF) patients toward multifetal pregnancy reduction before and after embryo transfer. STUDY DESIGN: Women seeking IVF consultation were surveyed before and after embryo transfer regarding their attitudes toward multifetal pregnancy reduction. RESULTS: Thirty one of 36 subjects completed the initial survey. The mean age was 32.9 years, 93% of subjects were Caucasian, and 61.3% were nulliparous. Most subjects described themselves as "pro-choice" (20 of 31, 64.5%). Overall, 22.6% (7 of 31) stated that they would never consider fetal reduction in a multifetal pregnancy and 77.4% (24 of 31) stated that they would consider multifetal pregnancy reduction. The threshold to consider fetal reduction was triplets. Prochoice subjects were significantly more likely to consider multifetal pregnancy reduction when compared to "prolife" subjects (p <0.01). Twelve of the 31 subjects underwent embryo transfer and completed the second survey. Patient attitude did not change significantly from the time of initial IVF consultation to after embryo transfer. CONCLUSION: Overall, women undergoing IVF would consider multifetal pregnancy reduction, and this view did not change after embryo transfer. Pro-choice subjects were more likely to consider multifetal pregnancy reduction. PMID- 17847764 TI - Extension of GnRH agonist through the luteal phase to improve the outcome of intracytoplasmic sperm injection. AB - OBJECTIVE: To investigate the effect of continuous administration of gonadotropin releasing hormone agonist (GnRHa) during the luteal phase in an intracytoplasmic sperm injection program. STUDY DESIGN: One hundred eighty-one women underwent a down-regulation protocol of GnRHa administered from the 21st day of the preceding cycle. Patients were randomized at initiation of stimulation by a computer generated list. Group 1 patients (n = 90) were continuously administered GnRHa for 12 days after embryo transfer, while in group 2 patients GnRHa was stopped on the day of human chorionic gonadotropin administration. RESULTS: Demographic parameters, infertility etiologies, number of gonadotropin ampules used, number of mature oocytes recovered, rates of testicular sperm usage, number of embryos transferred, and cycle and transfer cancellation rates were similar in both groups. Clinical pregnancy rates, implantation rates and live birth rates did not show a significant difference. CONCLUSION: Extending GnRHa treatment through the luteal phase appeared not to have a significant impact on pregnancy or implantation rates in intracytoplasmic sperm injection cycles. PMID- 17847765 TI - Novel bioadhesive patch-type system for photodynamic vulvodynia therapy after delivery of 5-aminolevulinic acid: preliminary evaluation. AB - OBJECTIVE: To assess the applicability of photodynamic therapy (PDT) in the management of vulvodynia whereby a novel, patch-type system, loaded with 5 aminolevulinic acid (ALA), was used to administer PDT to vulvar regions displaying the characteristics of vulvodynia. STUDY DESIGN: Eleven patients underwent PDT using a bioadhesive patch to deliver ALA over 4 hours. A nonlaser light source delivered 100 J cm(-2) to the target area using red light of 630 nm. Fluorescence of protoporphyrin IX was observed under ultraviolet light illumination, with no significant difference found between that produced after the first and second applications of the patch. RESULTS: There was a significant reduction (p= 0.0077) in overall symptoms after completion of treatment. No significant alleviation (p = 0.1088) in pain during intercourse was observed following treatment. Eight patients experienced a symptomatic response, while 3 exhibited no improvements in symptoms. No adverse reactions or worsening of reported symptoms was reported. CONCLUSION: The results suggest that PDT is of value in the management of vulvodynia, most probably as a viable option to conventional approaches. Further studies involving larger numbers of patients are required to confirm the efficacy of PDT in the management of vulvodynia. PMID- 17847766 TI - Coexisting ectopic and intrauterine pregnancies: a case report. AB - BACKGROUND: The simulated presence of intrauterine and extrauterine pregnancies is a rare condition. Diagnosis is difficult, accomplished on grounds of strong suspicion (as in assisted reproductive treatment cases), on the presence of predisposing factors (pathology of salpinx) or as a coincidental finding in the emergency room when a patient presents after an elective or spontaneous abortion. An intrauterine pregnancy may be discovered in a patient who presents with ectopic pregnancy. CASE: A 40-year-old multigravida was diagnosed with coexisting extrauterine and intrauterine pregnancies when she presented with a right ectopic pregnancy in the emergency room. The patient underwent partial right salpingectomy and an elective abortion. CONCLUSION: Patients who present with acute pelvic pain must be investigated for coexisting ectopic pregnancy even though they have a proven intrauterine pregnancy. Such an investigation is even more important if the patient is undergoing assisted reproductive treatment. In patients who have had spontaneous or elective abortion, especially in cases of a gestation <4 weeks, the differential diagnosis should include coexisting ectopic pregnancy. Failure to diagnose this condition can have serious consequences. PMID- 17847767 TI - Spontaneous uterine artery rupture during pregnancy in a woman with sickle cell disease: a case report. AB - BACKGROUND: Spontaneous rupture of uterine vessels during pregnancy is rare and usually involves uteroovarian veins. Presenting symptoms include acute-onset abdominal pain and maternal hypovolemic collapse due to hemoperitoneum. An atypical case of subacute uterine artery rupture at 27 weeks of gestation occurred in a woman with sickle cell disease. CASE: A 28-year-old, nulliparous woman with sickle cell disease was admitted at 27 weeks of gestation for sharp abdominal pain radiating to the right flank. The first diagnosis included acute renal colic and a sickling vasoocclusive crisis. One week after admission the patient experienced paroxysmal, diffuse abdominal pain associated with acute fetal distress requiring an emergency cesarean section. Laparotomy revealed an 800-mL hemoperitoneum. Active bleeding from a ruptured uterine artery was observed and successfully treated by selective suture. CONCLUSION: Spontaneous rupture of the uterine artery during pregnancy may present as a 2-step process. PMID- 17847768 TI - Rectal tear during normal vaginal delivery with an intact anal sphincter: a case report. AB - BACKGROUND: A rectal tear with an intact anal sphincter is an unusual presentation. Failure to recognize or repair perineal and rectal lesions increases the chance of fistulas and incontinence. CASE: A 37-year-old woman, para 1, was admitted with spontaneous onset of labor at 36 weeks following an uncomplicated pregnancy. During the active second stage of labor, spurting of amniotic fluid through the anus was noted. Labor progressed normally, and the patient delivered a healthy infant of 2.5 kg. Immediate per rectal examination revealed a large rectal tear with an undamaged anal sphincter. The defect was repaired, and the patient recovered completely. CONCLUSION: Systematic examination of the perineum, vagina and rectum should be done to assess the severity of damage after all vaginal deliveries in order to recognize occult as well as visible damage. It should be treated promptly to reduce postpartum morbidity. PMID- 17847770 TI - Don't ignore "unsolicited" reports. PMID- 17847769 TI - Successful management of a pregnant woman with HELLP syndrome, pulmonary edema, postpartum hemorrhage and acute renal failure, using early hemodialysis, intravenous immunoglobulin and noninvasive monitoring: a case report. AB - BACKGROUND: HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) with medical complications is a major cause of maternal mortality in pregnancy. A vicious cycle may occur without expeditious delivery and proper management. CASE: A woman with severe HELLP syndrome, hemolytic renal failure, pulmonary edema and postpartum hemorrhage was successfully managed using early hemodialysis, intravenous immunoglobulin (IVIG) and noninvasive hemodynamic monitoring. CONCLUSION: Pulmonary edema is easily managed by early hemodialysis. IVIG may be a viable treatment for thrombocytopenia and hemolysis but can induce reversible interstitial nephritis and membranous glomerulonephritis. PMID- 17847771 TI - Losing the fight against frivolous claims. PMID- 17847772 TI - Recertification made easier. PMID- 17847773 TI - 8 ways I improved my bottom line. PMID- 17847774 TI - My credo: knowledge intergrity respect empathy. PMID- 17847775 TI - Private practice or academia? PMID- 17847776 TI - [Laryngectomy as a salvage procedure of the patients with massive postradiation injury of the larynx]. AB - INTRODUCTION: Author discusses problems and treatment principles of patients with massive postradiation injury, who had laryngectomy procedure as a result of insufficience of the farmacological treatment. MATERIAL AND METHODS: There were 12 patients who were performed laryngectomy as a treatment of massive postradiation injury of the larynx in the period 1975-2005. We suspected presence of persistent neoplasm with postradiation changes. Seven laryngectomies were performed after confirmation of the neoplasm in 1-3 biopsies. Three patients were treated operatively without this confirmation in spite of two biopsies which were negatively, and two patients were treated in this way without biopsies. RESULTS: Two patients had tomour free postlaryngectomy specimens in the histopathological examinations, and among 10 others the reccurence of the tumour after radiotherapy was present during the post-laryngectomy histopathological examinations. In 7 cases this reccurence was proved with massive postradiation injury in endoscopic biopsies before laryngectomy. DISCUSSION: Author presents his own problems and presents methods of treatment of the patients with massive postradiation injury of the larynx described in literature. PMID- 17847777 TI - [Endoscopic surgical treatment of patients with isolated sphenoid sinus disease]. AB - INTRODUCTION: Cases of isolated lesions of the sphenoid sinus are rare. For descriptive purposes, clinicians divide them into inflammatory and non inflammatory with prevalence of the former. Symptoms of the sphenoid sinus disease are difficult to characterise, the most common of them being vague headache and visual disturbances. Thorough preoperative evaluation of the lesion is essential - nasal endoscopy must be performed and computerised tomography or magnetic resonance imaging results analysed. The purpose of the study is to present the assessment of endoscopic surgery outcome in the own group of patients with isolated sphenoid disease. MATERIAL AND METHODS: Clinical data of 22 subjects were analysed retrospectively. There were 5 patients with bacterial sinusitis, 6 with fungal sinusitis, 4 with allergic thickening of the mucous membrane with no evidence of bacterial or fungal infection, 2 with mucocele, 1 with sphenoid osteoma, 1 with inverted papilloma, 1 with a foreign body and 2 with cerebral fluid fistula. Each patient had preoperative nasal endoscopy and CT/MRI imaging performed. Then they underwent endoscopic transnasal sphenoethmoidectomy with removal of the lesion or closure of the fistula. The sphenoid sinus was approached through its front wall. RESULTS: The patients' postoperative course was uneventful. They noted improvement in all preoperative symptoms, except for bilateral oculomotor nerve paralysis in one individual, and were asymptomatic to ophthalmological examination. CONCLUSIONS: Isolated lesions of the sphenoid sinus, even very rare tumours like those presented here, can be in most cases safely approached and removed endoscopically. All risks of the method must be considered prior to the operation. High frequency of fungal sinusitis should be noted. PMID- 17847778 TI - [Endoscopic management of osteomas of the paranasal sinuses--own experience]. AB - Osteomas are relatively common, benign, slow-growing, often asymptomatic neoplasms of the paranasal sinuses, occurring mainly in frontal and ethmoid sinuses. Surgical removal is done if they extend beyond the boundaries of the sinus, keep enlarging, are localised in the region adjacent to the nasofrontal duct, or if signs of chronic sinusitis are present and, irrespective of their size, in symptomatic tumours. Progressive headaches and chronic inflammation of the adjacent mucous membrane are most common symptoms. Endoscopic surgery plays an important role in management of ethmoid, sphenoid and frontal osteomas. Aim. The aim of the paper was to report own experience in endoscopic treatment of patients with osteomas of the paranasal sinuses. Material and methods. 6 patients with osteomas of paranasal sinuses were included in the group, mean age 36 years (range 15-52). Most common involvement was ethmoid cells (3). There were also patients with frontal, maxillary and sphenoid osteoma. All tumours were removed under endoscopic giudance. Frontoethmoidectomy was performed to remove ethmoid and frontal osteomas. Antrotomy was used in case of maxillary involvement and sphenoethmoidectomy in the patient with sphenoid sinus osteoma. Sphenoid sinus was approached through its anterior wall with a Stammberger punch. All the tumours were removed using fine forceps. Results. No post-operative complications were observed. No recurrences were noted. All patients remain asymptomatic. Conclusions. Resection of small and medium size osteomas of the paranasal sinuses can be safely and radically performed using endoscopic techniques. It allows their radical resection and very good cosmetic effects. PMID- 17847779 TI - [The surgery voice rehabilitation after total laryngectomy with the Provox system]. AB - THE AIM OF STUDY: Comparison the voice quality of patients after total laryngectomy using the Provox 2 voice prosthesis and patients with esophageal speech and to discuss difficulties and complications related with its implantation. MATERIAL AND METHODS: The study group consists of 39 patients after total laryngectomy and Provox puncture. 36 patients underwent primary puncture, 3 patients - secondary puncture. 32 patients underwent radiotherapy. The time starting of speech learning was approx the 9th day after total laryngectomy and 1st-3th day after secondary implantation. The authors subjectively and objectively analyzed voice of 34 patients with fistular speech and it compared with esophageal speech of 10. The spectrograms analysis of the voice was based on Remacle's scale. The study showed juxtaposition of early and late complications of patients with voice prostheses. RESULTS: 90% of patients (35 patients) learned the fistular speech. The speech was louder and more intelligible than esophageal voice in subjective estimation. The fistular voice had higher of mean volume (61,1 dB vs. 59 dB), mean longer maximum phonation time (9,5 s vs. 2,2 s), mean higher base frequency FO (108 Hz vs. 87Hz) and smaller variability of FO based on mean Jitter ratio (3,8% vs. 6,6%), mean Shimmer ratio (23,18% vs. 23,52%) and mean HPQ ratio (127,34 vs. 141,73) than esophageal voice in objective estimation. Mean range of frequency of the speech was smaller but it was in higher frequencies. The most frequent type of spectrogram was 3th type in experimental group and 2nd type in control group. The mean lifetime of prostheses was 295 days. The most common cause of replacement of the prosthesis was leakage associated with mycosis infection (26 cases). Early complications were observed. The most frequent of them was infection around the fistula during supplementary radiotherapy (7 cases after primary puncture). The most frequent of later complications was widening of fistula and leakage around prosthesis (4 cases). CONCLUSIONS: Rehabilitation of patients after total laryngectomy is better using Provox system than learning esophageal speech (according to voice quality aspect). Using of voice prostheses in patients after total laryngectomy can combine with appearance of complications. PMID- 17847780 TI - [Post-laryngectomy pharyngocutaneous fistula--a continuing clinical problem]. AB - BACKGROUND: Pharyngocutaneous fistula following laryngectomy is a serious complication, and its incidence varies from 4% to 65%. The study's objective was to determine the incidence of post laryngectomy fistulas in patients operated in our department to establish whether specific factors predispose to fistula formation. METHODS: A retrospective study was performed in 573 patients who underwent laryngectomy. RESULTS: Between 1989 and 1999, 835 cases of laryngeal carcinoma were diagnosed, 690 were treated surgically, 573 of them underwent laryngectomy in our department. Of these patients, 545 (95,1%) had total laryngectomy, while 28 (4,9%) partial laryngectomy. In 538 cases the laryngectomy was combined with radical or functional neck dissection. The presence of early postoperative fistula was established in 65 of the 573 patients (11,3%). Our study could not verify reports that any specific factors were significantly related to fistula formation, the only factors that did show statistical significance were the preoperative patient's general health status and the kind of postoperative antibiotic therapy. CONCLUSIONS: On the base of literature review, the authors compare results obtained in the last decade of the 20 century with results obtained earlier. Although the incidence of post-laryngectomy pharyngocutaneous fistulas decreased in comparison with the fistula rate observed earlier, the problem is still unresolved, and the fistulae remain a serious complication of larynx oncology surgery. PMID- 17847781 TI - [Treatment of fungal infections of upper respiratory tract and ear]. AB - Fungi, in comparison with other pathogenic factors, have high pathogenicity. The number of fungal species which are able to infect people is over 500. The upper respiratory tract and ear have permanent contact with external environment which makes their ontocenoses open to continuous exchange of microorganisms of which they consist. In etiology of inflammatory processes 21 species which belonging to 3 genera (Zygomycota, Ascomycota, Basidiomycota) of fungi play important role. Administration of antifungal drugs can be: prophylactic, empiric preemptive and therapeutic. Physicians may prescribe antibiotics (mainly pollens: amphotericin B, natamycin and nystatin) and chemiotherapeutics (mainly azoles and fluorpirymidins, pigments, chlorhexidine and chlorquinaldol). In ENT practice topical and systemic drugs can be administrated. Topical lozenges include amphotericin B, clotrimazole, chlorhexidine or chlorquinaldol and oral gels: nystatin and miconazole. Some of drugs are in the form of suspension/solution, which can be used for inhalation, into the sinus, for swabbing or for lavage: amphotericin B, natamycin, nystatin, clotrimazol, flucytosine, miconazole, fluconazole, vorykonazole, caspofungin. It should be underlined that only a few of dugs can be absorbed from the digestive tract: flucytosine, fluconazole, itraconazole, ketoconazole, miconazole, vorykonazole. PMID- 17847782 TI - [Malignant tumors of the oral cavity and neck in clinic of maxillo-facial surgery in Poznan from 2002-2004]. AB - Increasing number of malignant neoplasms of the oral cavity and facial region as well as lower age of the patients hospitalized were the interest of the authors. MATERIAL AND METHODS: Clinical data from the years 2002-2004 were analysed in this paper. In this study the factors as: sex and age of patients, tumor localization, histological examinations, surgical treatment of the tumor and lymph nodes are reported. RESULTS: During the 3 years period there were 346 tumors of the oral cavity treated in Clinic of Maxillofacial Surgery in Poznan. Epidemiologic studies have revealed a increased number of squamous cell carcinomas and other malignant tumors as lymphomas, adenoid cystic carcinomas and sarcomas of the oro-facial region. The staging of the tumors is similar as in previous years. CONCLUSIONS: The study shows better knowledge about oral malignancies in dentists and general praticioners. The tumor patients are surgically treated earlyer as in previous years. PMID- 17847783 TI - [Submucosal bipolar radiofrequency therapy for treatment of turbinate hypertrophy]. AB - Disturbance of nasal airflow occurs in about 30% of human population. Turbinate hypertrophy is frequently the base of many nasal obturative diseases. The aim of this study was to determine short- term and long term effects of the radiofrequency therapy (RFT) for patients with turbinate hypertrophy. Forty- one patients with inferior turbinate hypertrophy (19 females and 22 males) were enrolled in this study prospectively. The examination included: rhinoscopy, subiective visual analogue scale (VAS) score, in which a patient described his symptoms in points from 0, (always very good nasal airflow) to 10 points (always total obstruction) and anterior rhinomanometry. The clinical assessment was before radiofrequency-turbinectomy and within the days 7 to 25 afther this therapy (follow-up 1) and 12 months later (follow-up 2). RFT was performed in local anesthesia (1% Lidocain) by means of CELON. Rhinoscopy before RFT revealed turbinate hypertrophy, which was decreased in the follow-up examination. Subjective improvement of nasal airflow was felt by 39 patients (95%) at follow up 1. At follow-up 2 fifteen patients (37%) reported a decreased nasal airflow when compared with the follow-up 1. Rhinomanometric results were better at follow up 1 for the left side (p = 0,0003), the right side (p = 0,0002) and both sides altogether (p = 0,0001). The improvement continued at follow-up 2 for the left side (p = 0,0004), the right side (p = 0,001) and both sides (p = 0,001) when compared with rhinomanometry before RFT. There were not statistically significant differences between the rhinomanometric results at follow-up 1 and follow-up 2. Bipolar radiofrequency thermal ablation is an effective method for the therapy of turbinate hypertrophy. PMID- 17847784 TI - [Nd:YAG laser assisted uvulopalatoplasty in the treatment of obstructive sleep apnea syndrome]. AB - INTRODUCTION: Surgical treatment of OSAS is focused on removal of narrowing that increase airway resistance in upper respiratory tract. Nd:YAG laser beam penetrates deeper into tissue than CO2 laser followed by superior scarification ability. In this study we investigate efficacy of surgery with Nd:YAG laser assisted uvuloplasty (LAUP). MATERIAL AND METHODS: The subject was 51 patients with OSAS treated in Department of Otolaryngology, Medical University of Gdansk during the 2004-2005 period. All patients underwent all-night PSG and the ESS (Epworth Sleepiness Scale) score was used to assess the daytime sleepiness. Surgery treatment was performed and all patients underwent LAUP and additionally lingual base laser vaporization, tonsillectomy and nasal surgery where needed. The postoperative control ENT examination including ESS and all-night PSG was performed after 6 months. RESULTS: Success was found in 29 patients, they achieved AHI<10 and ESS<12. In another 22 patients improvement at PSG parameters and ESS score were evaluated but they were still beyond normal range. Success was obtained in 14/16 patients with preoperative AHI I degree, 10/19 AHI II, and 4/16 AHI III. Nasal surgery for enlargement of airway passage was performed more frequently (25/32) in the group with success then in the group with partial improvement (9/19). Preoperative PSG parameters were better in patients with nasal obstruction. Patients with BMI> or =30 succeeded rarely (10/22) in compare with patients with BMI<30 (success in 24/29). Preoperative PSG parameters were better in patients with BMI<30. CONCLUSION: LAUP with Nd:YAG laser wit additional tonsillectomy, lingual base surgery and nasal surgery were needed is successful method for surgery at light and medium stage of OSAS in nonobese patients. PMID- 17847785 TI - [Video endoscopic analysis of eustachian tube function in children with middle ear pathology]. AB - Eustachian tube (ET) dysfunction play an important role in the development, persistence and recurrence of otitis media with effusion (OME) and chronic otitis. Evaluation of the type of obstruction in the cartilaginous portion of ET is important for decision concerning methods of treatment and prognosis of surgical outcome. The aim of this study was to identify characteristics of dynamic function of the pharyngeal orifice of ET in children with OME and chronic otitis by video endoscopy. Transnasal endoscopic examination of the nasopharyngeal opening of ET during swallowing was performed on 21 children - 13 with OME, 8 with chronic otitis. Video recording were made for dynamic slow motion analysis of ET dilation and closing processes. Most cases of ET dysfunction in children were obstrucive (81%), associated with mucosal oedema and hyperplasia. Dynamic type of dysfunction is caused by the reduced movement of the tensor veli palatini. Dynamic video analysis is useful in the identify type of ET dysfunction in children. Obstructive dysfuntion need diagnostic procedures for chronic infection, nasopharyngeal reflux and alergic diseases. PMID- 17847786 TI - Benign paroxysmal vertigo of childhood. AB - OBJECTIVE: To relate the authors' experience to the diagnosis and follow-up of patients with benign paroxysmal vertigo of childhood (BPV) who were followed-up at the Children's Hospital of Bydgoszcz between 1999 and 2004, and to review and discuss controversial issues regarding the disease. METHODS: Among 124 children suffering from vertigo 14 were classified as having BPV. All the children were submitted to differential diagnosis protocol which consisted of meticulous history, otolaryngological, ophthalmological, psychological, neurological examination, biochemical tests and standard neurootological examination including caloric tests. The children were followed-up and the tests were repeated if no improvement was observed. RESULTS: All the children suffered from episodic vertigo of variable intensity and frequency. All of them were neurologically intact. In 8 patients pathologic ENG results were found, only 1 patient with canal paresis could be considered as having peripheral lesion, 7 patients had central/mixed pathology. The follow-up was favorable in majority of patients. Six of them recovered completely, in 6 an improvement was noted and in 2 no improvement was observed. Three patients after remission of BPV attacks developed migraine. One child before development of BPV attacks suffered from paroxysmal torticollis of infancy. CONCLUSIONS: Childhood BPV is a disorder of vestibular system with the onset occurring mainly in preschoolers aged 1-7. Older children with the onset of BPV - like symptoms should be suspected for functional background of the disease. There are no typical ENG features for BPV. The only objective evidence of vestibular dysfunction is the presence of nystagmus during the attack. The disease is probably of vascular origin and there is strong evidence for close relationship between spasmodic torticollis, BPV and migraine. PMID- 17847787 TI - [Adenoma oxyphillicum an extremely rare case of tumour of the larynx end cancer lungs which are going together]. AB - There was presented an exstremely rare case of adenoma oxyphillicum of the larynx coexisting with the lung carcinoma. Diagnostical and medical conduct was throughly analyzed. It consisted such matters as detailed graphical examination, spliting of larynx, and radiotherapy and chemiotherapy of lung cancer. The authors want to call attention to limited use fullness of competent lungs X-ray in a-p projection in recognizing the early stadium of lung cancer. PMID- 17847788 TI - [Bleeding as an initial symptom of tonsillar carcinoma]. AB - The authors present the case of the patient suffering from recurrent bleeding from the palatine tonsil. A visual and tactile examination did not reveal any alteration to the tonsil. Following three recurrent bleeding episodes, we conducted an examination of the vessels (through MRI including vessel option) and consequently ruled out any possible presence of vessel alterations in the tonsil and in the adjacent tissues. Subsequently tonsillectomy was carried out. The histopathological examination revealed the presence of carcinoma in the tonsil's flesh, whereas the mucosa of the tonsil remained unaltered. Over the period of six months the patient had repeatedly been examined by experienced head and neck surgeons, none of whom found any abnormalities in the tonsil. No other symptoms of the tonsil carcinoma were detected in the patient. The authors underscore the rare occurence of the abovementioned symptoms in carcinoma of the tonsil. They note, however, that certain number of patients with the branchiogenic cyst exhibit the abovementioned symptoms of the tonsil carcinoma. PMID- 17847789 TI - [Atypical facial pains--sluder's neuralgia--local treatment of the sphenopalatine ganglion with phenol--case report]. AB - AIM: Chronic reccuring head and facial pain can be very difficult for successful treatment. Such a pain can be in some rare cases Sluder's sphenopalatine ganglion neuralgia. The aim of the study was to obtain the pain relief by local treatment in patients with Sluder's sphenopalatine ganglion neuralgia. METHODS: We described three cases of Sluder's neuralgia among all the seventeen patients with reccuring head and face pain that were seen in our department. In all these cases 4% Xylocaine was applied intranasally, into the region of shenopalatine ganglion, behind the posterior tip of the middle turbinate four times for ten minutes. According to Kern, the diagnosis of Sluder's neuralgia was confirmed only in cases where local anesthetic block of the sphenopaltine ganglion was successful. It means the patients were pain-free for at least an hour after application of Xylocaine, so they were qualified for phenolization and 88% phenol was applied on the cotton carriers (number of the applications depended on the patient). RESULTS: The total relief of pain of different duration was obtained in all the presented cases. CONCLUSION: The relief of pain obtained by intranasal phenolization of sphenopalatine ganglion in three patients shows it could be the effective treatment of Sluder's neuralgia. The patients were totally free from the pain and accompanying symptoms like nasal obstruction, rhinorrhea, epiphora or conjunctivitis. The relief period was different but the patients were satisfied with the effectiveness and simplicity of the treatment. They did not need to take the additional medications for months and were able to continue work. PMID- 17847790 TI - [Primary cholesteatoma of the middle ear and petrosal bone]. AB - Petrosal cholesteatomas are rare lesions, which may be primary or acquired in nature. We report a case of primary cholesteatoma in petrous bone occurring in 51 year old woman who presented with a unilateral facial nerve palsy and conductive hearing loss, despite normal tympanic membrane appearance. Early diagnosis was facilitated by computed tomography scanning and magnetic resonance imaging. Complete cholesteatoma removal was accomplished using a transtemporal supralabyrinthine approach, which allowed hearing preservation. Facial nerve function is the main complication of these lesion. We suggest that use of CT scanning and MRI in unilateral conductive hearing loss may allow the earlier detection of the most cases of petrosal cholesteatomas. PMID- 17847791 TI - [Malignant fibrohistiocytoma of the larynx]. AB - INTRODUCTION: Malignant fibrohistiocytoma is one of the rare neoplasms of the larynx. It has nonepithelial origin. The most common sites of the neoplasm are: limbs, trunk and retroperitoneal space. Other localizations within head and neck are very rare. There are 5 histologic types. The most common is pleomorphic type. It is built of histiocytes, fibroblasts and multinuclear giant cells. An examination of the neoplasms consists of microscopic and immunohistologic examination with identification specific tissue markers and intermediate filaments of proteins. Treatment methods of the neoplasms are radical surgery, radiotherapy, chemiotherapy and associate methods of therapy. Prognosis is very bad. MATERIAL AND METHODS: [corrected] We present 71 years old man with croak for four mounths. The tumor of the larynx was examined in laryngoscopy. Biopsy of the tumor confirmed malignant fibrohistiocytoma. Laser surgery (chordectomy) was used to treatment this tumor without radiotherapy. RESULTS: One year observation of the patient didn't show recurrence of neoplasm, but he had only croak. CONCLUSIONS: Malignant fibrohistiocytoma of the larynx doesn't differ from other malignant neoplasms of the larynx. Malignant fibrohistiocytoma of the larynx is very rare malignant neoplasms of the larynx. PMID- 17847792 TI - [Vestibular neuritis--a case description]. AB - Vestibular neuritis is a group of symptoms resulting from a sudden unilateral vestibular dysfunction. It seldom occurs in children (approximately 7%). Its etiology and pathogenesis are unknown, although most researchers consider viral infection to be a causative factor. The clinical symptoms appear rapidly, exacerbate within a few hours and include vertigos, accompanied by nausea, vomiting and paralytic nystagmus, which intensifies with head movements. This is a case of a 15-year-old boy, so far healthy and with normal psychomotor development, who was admitted to the hospital ward due to exacerbating vertigos accompanied by nausea and balance disorders. PMID- 17847793 TI - [Preseptal orbital abscess as a post-traumatic late complication--review of the literature and case report]. AB - Preseptal orbital cellulitis and orbital abscess are rare post-traumatic late orbital complications. Authors reported a case of anterior orbital abscess following craniofacial trauma in a 47-year-old men. Diagnostic procedures, therapeutic intervention were presented and literature reviewed. PMID- 17847794 TI - [Malignant melanoma of the auditory tube]. AB - Melanomas of the mucous membranes of airway tract constitute around 1% of the total melanomas of head and neck. The most common site of the tumor are the nasal and paranasal sinuses but melanomas of the oral cavity are described too. The location of malignant melanoma in the eustachian tube is very rare. We found five cases of this disease in the literature. In our article we present a 53-year-old woman with progressive left aural fullness and hearing impairment for two months. Clinical examination found left middle ear effusion. The nasopharyngoscopy revealed a bluish red, friable and granulomatous tumor occupying the whole pharyngeal orifice of the left auditory tube. The biopsy speciment was taken which established the diagnosis. Because of localization and spread of the melanoma we had a low opinion of surgical treatment and radiotherapy was recommended. The patient was under constant laryngologic and oncological observation. We did not notice the local recurrence of melanoma. She died two years after making the diagnosis because of the neoplasm dissemination. PMID- 17847795 TI - [Scared atrophy of the cervical part of trachea as an effect of prolongated intubation]. AB - Tracheal intubation is presently one of the basic medical procedures. It is connected with many different complications. One of them is tracheal stenosis, which occurs in 6-21 percent of patients after intubation of the trachea. In contrast to this high frequency of tracheal stenosis we didn't find any publications about complete atrophy of a big part of trachea after prolongated intubation and we describe a first case of such complication. The reasons and the possibilities of treatment in such situation are discussed. PMID- 17847796 TI - [Rehabilitation after total laryngectomy--vision and realization]. AB - Universality, early initiation, complexity and continuity - should be the main attributes of rehabilitation in patients after laryngectomy. The authors discuss the problem of universality and accessibility of rehabilitation in Poland. A great role in realization of this attributes played since 20 years the Polish Society of Laryngectomees. Till now the governmental help and the participation of the National Health Fund for the patients after laryngectomy is very limited. The early rehabilitation should be started before the operation and a particular note must be taken to the patient's changed vital situation after the surgical treatment. The complexity of the rehabilitation must cover the whole spectrum of rehabilitation; it means voice and speech therapy, the improvement of respiratory system function, the problems of respiratory air conditioning and the psychological as well as social psychological aspects. The authors describe a model of such a complex rehabilitation that can be provided in health resorts. In the postoperative period the role of the laryngectomee clubs and associations is very important to assure the continuity of rehabilitation. PMID- 17847797 TI - [History of tracheotomy]. AB - The present notion - tracheotomy, originates from the Latin words trachea - windpipe, which comes from the combination of Latin "tracheia" and Greek "arteria" indicating an uneven road, and "tome" - cut. Procedures of pharyngotomy have a long-lasting history. First similar operations were found on the ancient Egyptian clay tablets dating back to 3600 BC. Mentions of pharyngotomy operations were found in the papyrus called Ebers's Papyrus dating back to about 1550 BC, which can obviously be treated as an encyclopaedia of the medical knowledge that the ancient Egyptians possessed. Guidelines for the person performing pharyngotomy were described in Rig Veda - the holy scriptures of Hindi medicine, about 2000 BC. Asclepiads of Prussia in Bithynia (124-156 BC), a Greek physician practising in Rome, is commonly considered the father of pharyngotomy. In the 1st century BC he documented an operation similar to pharyngotomy. Procedures similar to pharyngotomy were conducted by Claudius Galenus of Pergamon (about 130-200 AD) who was treating gladiators at the beginning of his medical career. A precise description of the technique in pharyngotomy performed by the method adopted from Antilla (3rd century AD) was presented by Paulos Aeginata (625-690 AD), whereas in modern times the first surgical pharyngotomy was performed by Antonio Brasavola (1490-1554) in 1546. In those times pharyngotomy operations were applied as life saving procedures and were associated with a desperate fight for life. The best example is given by Sanctorio Santorius (1561-1636) who pierced the trachea lumen with a trocar. All the experiences connected with the pharyngotomy technique were collected by Lorenz Heister (1683-1758) and published in his work "Surgery" in 1716. Until the end of 18th century the work finally established views about performing pharyngotomy operations. In 1856 Eugeniusz Bonchut conducted the first pharyngotomy in a child with passing an intubation tube into the trachea lumen. The operation was performed according to theoretical assumptions by Armando Trausseau (1801-1867), whose contributions to emergency pharyngotomy methods are enormous. Finally, at the beginning of the 20th century Chevalier Jackson (1865-1958) set principles for surgical techniques in pharyngotomy that still remain in force. The return to Sanctorius's method and also adaptation of Selinger's method (1953) of cannulation of blood vessels turned out to be fundamental for the further development of transdermal pharyngotomy. The first set for multistage, dilatation pharyngotomy was provided by P. Ciaglia et al. in 1985. A one-stage pharyngotomy by special forceps was described by W. M. Griggs et al. in 1990. A technique of transdermal pharyngotomy from inside the trachea was presented in 1995 by A. Fantoni with his group. Modern methods of transdermal pharyngotomy are good complementary techniques for classical methods of pharyngotomy in both emergency and chronic cases. PMID- 17847798 TI - [The significance of Karol Gilewski (1832-1871) for the Polish laryngology]. AB - The professional and scientific activities of Karol Gilewski (1832-1871), one of the famous Cracovian physicians, the professor of the Jagellonian University are described first of all. His treatise on laryngofissure and laryngeal polyps in 1865 is presented widely. This is a second scientific work in Polish medical literature on this subject. The cases of laryngeal scleroma and laryngeal and cutaneous syphilis are also described. PMID- 17847799 TI - [Summary after the First Country Educational Meeting of Hospital Directors, Otolaryngologic Departments, Lichen, Poland]. PMID- 17847800 TI - Attempts to probe the ozone layer and the ultraviolet-B levels of the past. AB - To get a proper perspective on the current status of atmospheric ozone, which protects the biosphere from ultraviolet-B (UV-B; 280-315 nm) radiation, it would be of value to know how ozone and UV-B radiation have varied in the past. The record of worldwide ozone monitoring goes back only a few decades, and the record of reliable UV-B measurements is even shorter. Here we review indirect methods to assess their status further back in time. These include variations in the Sun's emission and how these affect the atmosphere, changes in the Earth's orbit, geologic imprints of atmospheric ozone, effects of catastrophic events such as volcanic eruptions, biological proxies of UV-B radiation, the spectral signature of terrestrial ozone in old recordings of star spectra, and the modeling of UV-B irradiance from ozone data and meteorological recordings. Although reliable reconstructions do not yet extend far into the past, there is some hope for future progress. PMID- 17847801 TI - Vulnerability to climate variability and change in East Timor. AB - This paper presents the results of a preliminary study of climate vulnerability in East Timor. It shows the results of projections of climate change in East Timor. The country's climate may become hotter, drier, and increasingly variable. Sea levels are likely to rise. The paper then considers the implications of these changes on three natural resources--water, soils, and the coastal zone--and finds all to be sensitive to changes in climate and sea level. Changes in the abundance and distribution of these resources is likely to cause a reduction in agricultural production and food security, and sea-level rise is likely to damage coastal areas, including Dili, the capital city. PMID- 17847802 TI - Soil climate and decomposer activity in Sub-Saharan Africa estimated from standard weather station data: a simple climate index for soil carbon balance calculations. AB - Soil biological activity was calculated on a daily basis, using standard meteorological data from African weather stations, a simple soil water model, and commonly used assumptions regarding the relations between temperature, soil water content, and biological activity. The activity factor r(e_clim) is calculated from daily soil moisture and temperature, thereby taking the daily interaction between temperature and moisture into account. Annual mean r(e_clim) was normalized to 1 in Central Sweden (clay loam soil, no crop), where the original calibration took place. Since soils vary in water storage capacity and plant cover will affect transpiration, we used this soil under no crop for all sites, thereby only including climate differences. The Swedish r(e_clim) value, 1, corresponds to ca. 50% annual mass loss of, e.g., cereal straw incorporated into the topsoil. African mean annual r(e_clim) values varied between 1.1 at a hot and dry site (Faya, Chad) and 4.7 at a warm and moist site (Brazzaville, Congo). Sites in Kenya ranged between r(e_clim) = 2.1 at high altitude (Matanya) and 4.1 in western Kenya (Ahero). This means that 4.1 times the Swedish C input to soil is necessary to maintain Swedish soil carbon levels in Ahero, if soil type and management are equal. Diagrams showing daily r(e_clim) dynamics are presented for all sites, and differences in within-year dynamics are discussed. A model experiment indicated that a Swedish soil in balance with respect to soil carbon would lose 41% of its soil carbon during 30 y, if moved to Ahero, Kenya. If the soil was in balance in Ahero with respect to soil carbon, and then moved to Sweden, soil carbon mass would increase by 64% in 30 y. The validity of the methodology and results is discussed, and r(e_clim) is compared with other climate indices. A simple method to produce a rough estimate of r(e_clim) is suggested. PMID- 17847803 TI - Combating land degradation through participatory means: the case of Swaziland. AB - This paper examines a community grazing project to rehabilitate degraded land in Swaziland. Using data from interviews, questionnaires, and focus groups, we show that the ways in which participatory, decentralized approaches to natural resource management play out at the local level are closely linked to national level power structures. The successes and issues that emerge at different stages of the grazing project reflect local socioeconomic priorities and show how people manage their time and labor according to household livelihood goals. However, the project favored the interests of cattle owners who were already the more socially and politically powerful members of the community. We argue that for participatory natural resource management to be more meaningful to communities, projects should focus on local ecological priorities, rather than addressing the environmental concerns that are rooted within existing dominant power structures. This requires change to social and political relationships across levels and the building of new institutions. PMID- 17847804 TI - Characterizing and comparing backcountry trail conditions in Mount Robson Provincial Park, Canada. AB - Two backcountry trails located within the Mount Robson Provincial Park boundaries in British Columbia, Canada, are compared for the type of ecological characteristics and the influence of topographical use level and management on trail degradation. Data on five trail impact variables were collected at 68 fixed line transects, and information on management features, use level, and water related problems were based on a survey of 31 km of trails. Results show that the two trails are similar in several ecological characteristics. The Berg Lake Trail (BLT), considered to be highly used and intensively managed, had more significant ecological problems than did Mount Fitzwilliam Trail (FWT), considered to be less highly used and intensively managed. However, ecological impacts on the FWT appear to be statistically no less different than on the BLT. It is concluded that effective trail management can mitigate many ecological problems that result due to the natural topographic conditions and use levels. PMID- 17847805 TI - Mercury pollution trends in subarctic lakes in the northern Swedish mountains. AB - Despite many years of research about mercury pollution, data concerning high latitude regions of Europe are limited, particularly studies of long-term temporal trends. It is not clear whether the mercury load at high latitudes follows the recent decreasing trends in European mercury emissions or whether the load is still high because of continuing global emissions. In this study we use sediments from 12 lakes, located above the Arctic Circle in the Swedish mountains, to assess the past and recent mercury pollution situation, especially for the last 200 y. The mercury load increased clearly in sediment deposited from the late 19th or early 20th century to a peak between 1960 and 1990. This peak represents an enrichment of 1.4 to 4.2 times over background concentrations. This enrichment is comparable with enrichments in sediments from lower latitudes as well as other Arctic regions. Since the 1990s mercury concentration has declined in 8 of the 12 lakes, i.e., similar to emission trends in Europe. PMID- 17847806 TI - Ethnobotanical skills and clearance of tropical rain forest for agriculture: a case study in the lowlands of Bolivia. AB - Indigenous peoples are often considered potential allies in the conservation of biological diversity. Here we assess whether ethnobotanical skills of indigenous people contribute to a reduction in the clearance of tropical rain forest. We measured ethnobotanical skills of male household heads and area of rain forest cleared for agriculture among 128 households of Tsimane', a native Amazonian group in Bolivia. We used multivariate regressions to estimate the relation between ethnobotanical skills and area of rain forest cleared while controlling for schooling, health status, number of plots cleared, adults in household, and village of residency. We found that when the ethnobotanical skills of the male household head were doubled, the amount of tropical rain forest cleared per household was reduced by 25%. The association was stronger when the area of old growth forest cleared was used as the dependent variable than when the area cleared from fallow forest was used as the dependent variable. People who use the forest for subsistence might place a higher value on standing forest than people who do not use it, and thus they may be more reluctant to cut down the forest. PMID- 17847807 TI - Disharmony between society and environmental carrying capacity: a historical review, with an emphasis on China. AB - Nature can survive without humans, but humans cannot survive without nature. Despite a clear understanding of this dependency, humans continue to exist in disharmony with nature, and our current environmental and human dilemmas reflect old problems with a long history. Societies have historically experienced many transitions from harmony between nature and society to a crisis of disharmony, followed by a subsequent transition from crisis to harmony. Such ecological crises arise when society no longer practices sustainable consumption of resources within the limits imposed by the environmental carrying capacity. Over the long term, the growth in human desires has always exceeded the growth in the environmental carrying capacity. Science, technology, and social institutions must all be improved to resolve the ecological crises that arise from this imbalance. This paper discusses how increasing understanding of the problem by the public and by decision makers is the key to minimizing the undesirable impacts of the coming bottleneck for sustainable development. Furthermore, we emphasize how this awareness must be translated into fundamental political and economic changes. PMID- 17847808 TI - Reevaluation of ENCORE: support for the eutrophication threshold model for coral reefs. AB - The results from the multimillion dollar Enrichment of Nutrients on Coral Reefs Experiment (ENCORE) on One Tree Island Reef (OTIR) suggest that increased nutrient loads to coral reefs will have little or no effect on the algal growth rates and, hence, on the associated effects that increased algal growth might have on the functioning and stability of coral reefs. However, a comparison of the concentrations of nutrients within the OTIR lagoon with the proposed nutrient threshold concentrations (NTC) for coral reefs suggests that all sites, including the control sites, were saturated with nutrients during ENCORE, and, hence, one would not expect to get any differences between treatments in the algal-growth related measurements. Thus, ENCORE results provide strong support for the proposed NTCs and support the ecological principle that algal productivity and, consequently, the functioning of coral reefs are sensitive to small changes in the background concentrations of nutrients. The principal conclusion of ENCORE, namely that the addition of nutrients did not cause the "pristine" OTIR to convert from coral communities to algal dominated reefs, is contrary to the fact that there was prolific macroalgal growth on the walls and crests of the experimental microatolls by the end of ENCORE. PMID- 17847809 TI - Geomarkers versus biomarkers: paleoenvironmental and astrobiological significance. PMID- 17847810 TI - Wastewater management through biomass of Azolla pinnata: an eco-sustainable approach. PMID- 17847811 TI - Two monitors are better than one. PMID- 17847812 TI - Dropping an "unpleasant" patient. PMID- 17847813 TI - Making better decisions. PMID- 17847814 TI - Office design that works. PMID- 17847815 TI - Implementing an EHR: going live is no snap. PMID- 17847816 TI - Will an EHR affect your malpractice risk? PMID- 17847817 TI - A different perspective. PMID- 17847818 TI - Are you raising false hopes? PMID- 17847819 TI - Evaluation of biological and economic efficiency of smallholder pig production systems in North Vietnam. AB - This study evaluates smallholder pig production systems in North Vietnam, comparing a semi-intensive system near a town with good market access, where a Vietnamese improved breed has replaced the indigenous pig breed, and an extensive system away from town, where the indigenous breed still prevails. Fieldwork was conducted in 64 households in four villages. Repeated farm visits yielded 234 structured interviews. Data were analysed by linear models and non-parametric tests. Production inputs and outputs were quantified, and feed use efficiency and economic efficiency were assessed. The gross margin was higher for semi-intensive production with the improved breed, while the benefit-cost ratio was higher under extensive conditions with the indigenous breed. The net benefit did not differ between systems. Twenty-four per cent of farmers yielded a negative net benefit. In one village under extensive conditions, live weight output from indigenous sows with crossbred offspring compared positively with the output from semi intensive production with improved genotypes, but was associated with high inputs, making production inefficient. Results indicate that improved genotypes might not be an efficient production alternative for saving-oriented production with limited resource supply. Suitability of evaluation parameters, farmers' production aims, and factors impacting the production success in different systems are discussed. PMID- 17847821 TI - Effect of diet on the metabolic profile of ostriches (Struthio camelus var. domesticus). AB - In order to study the metabolic profile of ostriches in relation to diet, 40 animals of both sexes were divided equally into two groups and fed two diets ad libitum consisting, on a dry matter basis, of the same commercial concentrate (60%) for the two groups and of corn silage (group A) or alfalfa hay (group B). In the morning, after about 12 h of fasting, blood was collected from the wing vein. The following haematological parameters were determined with an automatic system (Ektachem 250 analyser, Kodak): glucose, cholesterol, triglycerides, lactate (LAC), total protein (TP), uric acid, total bilirubin (Tbil), creatinine (CREA), calcium (Ca), magnesium (Mg), phosphorus (P), sodium (Na), potassium (K), chloride (Cl-), iron (Fe), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), cholinesterase (ChE), alpha amylase (Amyl), lipase (LIP) and gamma-glutamyltrasferase (GGT). Diet significantly affected some parameters of the metabolic profile. Indeed, owing to the presence of alfalfa hay in the diet, group B showed, in comparison to group A, significantly higher values of uric acid (222.5 vs 387.5 mmol/L, p < 0.01), GGT (8.50 vs 11.3 U/L, p < 0.05), Tbil (8.50 vs 10.7 mmol/L, p < 0.05), Ca (2.41 vs 2.83 micromol/L, p < 0.01), Mg (1.01 vs 1.18 micromol/L, p < 0.05) and K (2.71 vs 3.16 micromol/L, p < 0.01). The levels of creatinine (27.3 vs 32.6 mmol/L, p < 0.05) and AST (344.9 vs 461.4 U/l, p < 0.01) were also higher for group B. PMID- 17847820 TI - Performance and nematode infection of ewe lambs on intensive rotational grazing with two different cultivars of Panicum maximum. AB - The daily live weight gain (DLWG), faecal nematode egg counts (FEC), and packed cell volume (PCV) of Suffolk, Ile de France and Santa Ines ewe lambs were evaluated fortnightly for 56 days in the dry season (winter) and 64 days in the rainy season (summer) of 2001-2002. The animals were distributed in two similar groups, one located on Aruana and the other on Tanzania grass (Panicum maximum), in rotational grazing system at the Instituto de Zootecnia, in Nova Odessa city (SP), Brazil. In the dry season, 24 one-year-old ewe lambs were used, eight of each breed, and there was no difference (p > 0.05) between grasses for DLWG (100 g/day), although the Suffolk had higher values (p < 0.05) than the other breeds. In the rainy season, with 33 six-month-old ewe lambs, nine Suffolk, eight Ile de France and 16 Santa Ines, the DLWG was not affected by breed, but it was twice as great (71 g/day, p < 0.05) on Aruana as on Tanzania grass (30 g/day). The Santa Ines ewe lambs had the lowest FEC (p < 0.05) and the highest PCV (p < 0.05), confirming their higher resistance to Haemonchus contortus, the prevalent nematode in the rainy season. It was concluded that the best performance of ewe lambs on Aruana pastures in the rainy season is probably explained by their lower nematode infection owing to the better protein content of this grass (mean contents 11.2% crude protein in Aruana grass and 8.7% in Tanzania grass, p < 0.05) which may have improved the immunological system with the consequence that the highest PCV (p < 0.05) observed in those animals. PMID- 17847823 TI - Analysis of size and conformation of native Creole goat breeds and crossbreds used in smallholder agrosilvopastoral systems in Puebla, Mexico. AB - Liveweight (LW) of does and bucks of the native Creole goat breed and crosses of Creole does and Nubian bucks, aged 1.5-5 years, were recorded and body traits including: head length (HL), head width (HW), body length (BL), trunk length (TL), chest girth (CG), abdominal perimeter (AP), rump length (RL), and height at withers (HW) were measured to develop equations for predicting LW from the body measurements. Weight, sex, breed and kidding date of 354 kids were recorded at birth, and LW of the kids was measured monthly for one year to determine the effect of kidding season on growth rate. Bucks had higher (p < 0.05) body measurements than the does (HL 15.1 +/- 0.1 vs 16.6 +/- 0.2 cm; BL 97.6 +/- 0.4 vs 104.6 +/- 1.2 cm; CG 78.8 +/- 0.4 vs 79.9 +/- 1.0 cm; AP 82.4 +/- 0.5 vs 87.2 +/- 1.1 cm; HW 62.7 +/- 0.4 vs 70.1 +/- 0.8 cm). With the exception of TL, F2 does had higher (p < 0.05) body measurements and LW (28.8 +/- 1.5 vs 27.7 +/- 0.5 kg) than Creole does. The body traits of the F1 does were similar (p > 0.05) to those of Creole does with the exception of HL, BL and HR. The F2 kids were heavier (p < 0.05) at birth (3.31 +/- 0.1 vs 2.60 +/- 0.1 kg) and grew faster than the Creole kids. Male kids were heavier (p < 0.05) at birth (3.21 +/- 0.10 vs 2.73 +/- 0.13 kg), and grew faster than female kids. Season had a significant effect on birth weight. The results showed that LW of Creole goats and Creole x Nubian does could be estimated in the field using body traits. Birth weight and growth rate of kids could be improved by management practices that affect season of kidding. PMID- 17847822 TI - Effect of semen collection frequency on seasonal variation in sexual behaviour, testosterone, testicular size and semen characteristics of tropical hair rams (Ovis aries). AB - The purpose of this study was to examine the effect of day length on seminal characteristics, testicular size, sexual behaviour and testosterone (T4) concentration in pelibuey rams subjected to different semen collection frequencies. eighteen intact males were assigned randomly to one of two semen collection frequencies: in the high rate (HR) treatment, two ejaculations per week were obtained from each ram; one ejaculation every two weeks was collected under the low rate (LR) treatment. All animals were housed individually in contiguous 5 m x 5 m wire mesh pens and evaluated over a 12-month period. At the beginning of the experiment rams were 20 months old and 40-50 kg in weight. All rams ejaculated and produced semen throughout the year. Semen volume, sperm per ejaculation, testicular circumference and testicular volume were significantly (p < 0.05) greater during short days in all rams, regardless of the semen collection frequency, with the exception of sperm concentration, for which no variation was found in hr individuals, and reaction time and T4 levels, for which no variation was found in IR males. Rams subjected to HR collection were more affected by the short-day photoperiod than rams collected twice per week, exhibiting greater reduction (p < 0.05) in time to achieve their first ejaculation and in sperm per ejaculation, as well as greater increases (p < 0.05) in T4 concentration than IR rams (14.65 +/- 1.22 vs 23.53 +/- 5.34 s, (3.37 +/- 0.17) x 10(9) vs (3.52 +/- 0.20) x10(9) sperm and 8.68 +/- 0.44 vs 6.85 +/- 0.74 ng/ml, respectively). It was concluded that: (a) the magnitude of the seasonal effects was not sufficient to prevent the rams being used for breeding throughout the year, and (b) seasonal variation within variables was affected differently between semen collection frequencies. PMID- 17847824 TI - The effect of the control of endo- and ectoparasites on weight gains in crossbred cattle (Bos taurus taurus x Bos taurus indicus) in the central region of Brazil. AB - Endo- and ectoparasite infections are among the most important causes of disease and production losses in beef cattle in tropical and subtropical regions. Nevertheless, most treatments are given without epidemiological information and without evaluating their effect on the development of the animals. In this work we present the results of a study of the effect of treatments against endo- and ectoparasites in crossbred steers, during three cycles of field trials in the Brazilian Cerrado region. Three anthelmintic treatments during the winter and three acaricidal treatments during the spring/summer provided significant additional weight gain in three and two experimental trials, respectively. In the trials, steers treated for gastrointestinal nematodes gained a mean of 33 kg more and those treated for ectoparasites had additional mean weight gains of 13 kg compared with non-treated steers. PMID- 17847825 TI - Effect of supplementing a high-protein ram press sunflower cake concentrate on smallholder milk production in Zimbabwe. AB - Ram press sunflower cake protein concentrate was formulated locally and its effect on the performance of dairy cows was compared with that of a commercial dairy concentrate. The effects of concentrate on roughage dry matter intake, milk yield and milk composition, live weight and calving intervals were similar for all concentrates, which indicated that the home grown dairy concentrates were as effective as the dairy commercial concentrate. The lack of significant differences in the concentrations of rumen NH3-N, pH, VFAs and total AA in all the cows between concentrate types supported this. The results indicated that in the low-resource and low-input production systems, crossbreds were as productive as Jersey and Red Dane cows. The exotic cows were more susceptible to tick-borne diseases and mastitis, and showed higher incidences of calving problems and retained placenta compared with crossbred cows. The economics of feeding ram press sunflower concentrate were compared with those of a commercial dairy concentrate on the performance of crossbred, Red Dane and Jersey cows. The gross margin was higher when feeding sunflower cake than when feeding commercial dairy concentrate (p < 0.05). PMID- 17847826 TI - Prevalence and distribution of gastrointestinal helminths and their effects on weight gain in free-range chickens in Central Zambia. AB - Examination of helminths from gastrointestinal tracts of 125 free-range chickens in Zambia revealed a 95.2% prevalence rate. The species and their prevalences were: Allodapa suctoria (85.6%), Tetrameres americana (80.8%), Ascaridia galli (28.8%), Gonglonema ingluvicola (50.4%), Raillietina spp. (81.6%) and Heterakis gallinarum (32.8%). No trematodes or Syngamus trachea were found. Mixed infections accounted for 88.2% as compared to 7.2% of single infections. Effects of helminthoses on weight gain were investigated in 100 growing chickens randomly assigned to treatment (levamisole) and untreated control groups. There was a significant mean (+/- SEM) weight gain (grams) of 812.8 +/- 51.4 in the treatment group and 623 +/- 57.4 in the control group (p < 0.01). The mean (+/- SEM) worm burdens from the control group and the treatment group were 96.3 +/- 5.61 and 22.05 +/- 2.61, respectively. These results confirm the higher risk of helminth infections in free-range systems and may explain the deleterious effects in chickens. PMID- 17847827 TI - Public trust and privacy in shared electronic health records. AB - The development of information and communication technology in health care, also called eHealth, is expected to improve patient safety and facilitate more efficient use of limited resources. The introduction of electronic health records (EHRs) can make possible immediate, even automatic transfer of patient data, for health care as well as other purposes, across any kind of institutional, regional or national border. Data can thus be shared and used more effectively for quality assurance, disease surveillance, public health monitoring and research. eHealth may also facilitate patient access to health information and medical treatment, and is seen as an effective tool for patient empowerment. At the same time, eHealth solutions may jeopardize both patient safety and patients' rights, unless carefully designed and used with discretion. The success of EHR systems will depend on public trust in their compatibility with fundamental rights, such as privacy and confidentiality. Shared European EHR systems require interoperability not only with regard to technological and semantic standards, but also concerning legal, social and cultural aspects. Since the area of privacy and medical confidentiality is far from harmonized across Europe, we are faced with a diversity that will make fully shared EHR systems a considerable challenge. PMID- 17847828 TI - Dangerous patients and duties to warn: a European human rights perspective. AB - The recent case of David Bradley, who shot and killed four members of his family after telling his doctor he 'wanted to kill someone', has raised the question of whether a healthcare professional could ever be held liable for failing to take steps to constrain a potentially dangerous patient. Until recently, it was considered that the United Kingdom courts would be reluctant to impose a duty to protect third parties. However, the European Court of Human Rights' decision in Osman v UK--while not directly concerning healthcare professionals--has opened the door for just such a duty. When this duty will arise, and how it can be discharged, remain challenging questions. Furthermore, healthcare professionals face the unenviable task of balancing competing duties, in which the rights--and safety--of their patients must also be borne in mind. PMID- 17847829 TI - Ambiguity of the embryo protection in the Human Rights and Biomedicine Convention: experiences from the Nordic countries. AB - Until 1998 research on in vitro human embryos concentrated on the issues related to assisted reproduction. The situation changed dramatically when the first scientific report on the laboratory culture of human embryonic stem cells was published. This scientific breakthrough with new therapeutic promises put human embryo into a new, more vulnerable position. Combined with creation of embryos via somatic cell nuclear transfer, it inveigles into mass production of embryos, first for scientific purposes, but later perhaps for the healing of people. This article examines the efficacy of the Convention on Human Rights and Biomedicine in protecting embryos in this new era of embryo research. The interpretative latitude of Article 18 of the Convention is demonstrated, and legislation in three Nordic countries with highly variable approach to embryo research regulation is analysed. I examine how this divergence is possible in the light of the Convention text. In the end, potential reasons for variation in regulation in the otherwise similar Nordic countries are discussed, as well as under what conditions harmonisation of regulation on embryo research, a highly value-charged matter, could be possible at the European level. PMID- 17847830 TI - The rights of people with an intellectual disability in The Netherlands: from restriction to development. AB - The purpose of this article is to discuss whether the right to self-determination is the only and the best principle in health law for care providers to support their clients with an intellectual disability, or whether other principles such as the right to development, the right to good care and the right to protection might lead to a better protection of the rights of clients in this field of care. The right to self-determination is the central principle in the Dutch Psychiatric Hospitals (Compulsory Admissions) Act, which at times seems less than beneficial to the legal position of persons with an intellectual disability. The question is whether a new (alternative) legal framework, in which the focus shifts to the right to good care and the right to development, might improve the legal position of people with an intellectual disability. PMID- 17847831 TI - Striking the right balance: patient's rights and opposing interests with regard to health information. PMID- 17847832 TI - Data protection, genetics and patents for biotechnology. PMID- 17847833 TI - Freedom of information and healthcare data--the first UK appeal: Common Services Agency v the Scottish Information Commissioner. PMID- 17847834 TI - European Court of Justice. CJEC 2007/1, Case C-444/05, Aikaterini Stamatelaki/NPDD Organismos Asfaliscos Eleftheron Epangelmation (OAEE). PMID- 17847835 TI - European Court of Human Rights. ECHR 2007/5 case of Wedler v. Poland, 16 January 2007, no. 44115/98 (Fourth Section). PMID- 17847836 TI - European Court of Human Rights. ECHR 2007/6 Case of Tysiqc v. Poland, 20 March 2007, no. 5410/03 (Fourth Section). PMID- 17847837 TI - European court of human rights. ECHR 2007/7 Case of Istratii and others v. Moldova, 27 March 2007, no. 8721/05, 8705/05 and 8742/05 (Fourth Section). PMID- 17847838 TI - Mosquitoes of the mangrove forests of India: part 5--Chorao, Goa, and Vikhroli, Maharashtra. AB - Mosquitoes of 14 species belonging to 9 subgenera and 9 genera were recorded in Chorao mangroves of Goa, and 12 species belonging to 9 subgenera and 7 genera in the mangroves of Vikhroli, Maharashtra, in India. Genera recorded were Aedes, Anopheles, Armigeres, Culex, Mansonia, Ochlerotatus, Orthopodomyia, Toxorhynchites, Uranotaenia, and Verrallina. Species common to both the mangroves were Ae. albopictus, Ae. novalbopictus, An. subpictus, Cx. sitiens, Oc. wardi, Ur. atra, and Ve. lugubris. Tree holes, crab holes, and swamp pools were the common larval habitats in Chorao, but tree holes were absent in Vikhroli. Adults of Ae. albopictus, Ae. novalbopictus, Ar. subalbatus, Cx. gelidus Cx. sitiens, Ma. indiana, Ur. atra, and Ve. lugubris were found landing on humans. Aedes novalbopictus, Oc. wardi, and Or. anopheloides are new records for the state of Goa. PMID- 17847839 TI - Redescription of the pupa of Culex restuans and a comparison with Culex nigripalpus. AB - The pupa of Culex restuans is redescribed in detail with a chaetotaxal table and a full illustration. The chaetotaxy of the pupa of Cx. restuans is compared with that of Cx. nigripalpus, the primary vector of St. Louis encephalitis and West Nile virus in Florida. PMID- 17847840 TI - Spatiotemporal monitoring of floodwater mosquito dispersal in Osijek, Croatia. AB - This paper demonstrates the possibility of using geostatistics to monitor the dispersal of mosquitoes for mosquito control programs at the municipal level. The case study objective was to quantify the dispersal of floodwater mosquitoes from the natural marshland Kopacki rit into the city of Osijek, Croatia, and to analyze the main factors controlling it. Fifty thousand adult Aedes vexans, Ochlerotatus sticticus, and Ochlerotatus caspius mosquitoes were marked with a powdered fluorescent pigment and released from the southern part of Kopacki rit on April 28, 2004. Forty CO2-baited Centers for Disease Control and Prevention traps were set in the area of the municipality of Osijek (171 km2) and were monitored for 10 days. A total of 582,471 mosquitoes were captured and examined in the laboratory. The mosquito counts from different sites were then interpolated using ordinary kriging and visualized dynamically to detect the dominant migrational directions. Mosquito dispersal and frequency were greatly influenced by wind speed (r = 0.82). The marked mosquitoes were found at 12 sites located from 1 km to 11.7 km away from the release point. The recapture rate was 0.044% (54% Oc. sticticus, 32% Ae. vexans, and 14% Oc. caspius). Based on the Lincoln index, the estimated total population size for floodwater mosquitoes in the study area ranged from 875 million to 2.0 billion mosquitoes. Limitations of the approach, recommendations for the improvement of the monitoring network, and spatial predictions are further discussed. PMID- 17847841 TI - Constructed wetlands for sewage effluent treatment and mosquito larvae at two sites in subtropical Australia. AB - This study of 2 wetlands in subtropical Australia, constructed to treat sewage effluent, examined the relationships between dips positive for mosquito larvae and water quality, operational status of the system, vegetation, and nontarget macroinvertebrates. One site is inland and the other is close to the coast. Larvae of disease vector mosquitoes were present at various times in the wetlands, especially in summer and autumn. The proportion of early instars (1st and 2nd) was greater than that of later ones (3rd and 4th). Dissolved oxygen was negatively, and temperature was positively, associated with the proportion of dips containing larvae. For the coastal site we noted that larvae were more common during draw-down of water for maintenance and also as the system started to come online. Vegetation associated with larvae included dense Typha orientalis and algae. Where there were several types of plants, such as at the coastal site, plant density and water depth were not significantly related to larval presence. Where there were several types of macroinvertebrates there were fewer dips positive for larvae. To provide water treatment capacity and minimal mosquito production we concluded that design should include a variety of plant types, discouraging low dissolved oxygen (for example, by aeration) and ongoing maintenance should be carried out in winter or spring, when mosquitoes are fewer than in summer. PMID- 17847842 TI - Field comparison of Bermuda-hay infusion to infusions of emergent aquatic vegetation for collecting female mosquitoes. AB - Field experiments were conducted in east-central Alabama in 2003 and 2004 to compare the attractiveness of selected gravid-trap infusions to ovipositing female mosquitoes. Comparisons were made among infusions of the following plants: Bermuda hay, Cynodon dactylon, and 3 species of emergent aquatic plants typical of Culex larval habitats, i.e., soft rush, Juncus effusus; a common sedge, Rhynchospora corniculata; and broad-leaf cattail, Typha latifolia. Experiments were conducted at a site in Lee County, AL, with an abundance of common nuisance mosquitoes, including Culex quinquefasciatus and Aedes albopictus. Carbon dioxide baited miniature light traps were operated concurrently with gravid traps to provide an activity index of mosquito species at the site. Gravid traps with hay infusion collected the greatest numbers of Cx. quinquefasciatus and Culex restuans females (2003). The results indicate that hay infusion is highly attractive to Cx. quinquefasciatus and is the infusion of choice for collecting females of this species in gravid traps. In the case of Ae. albopictus, infusions were not determined to be significantly different from one another in their attractiveness to gravid females. In general, females of Cx. quinquefasciatus and Cx. restuans demonstrated selectivity when choosing an oviposition site, whereas Ae. albopictus females did not. Factors associated with the oviposition biology of the latter species most likely account for their lack of preference for any single infusion type. PMID- 17847843 TI - Constant temperature and time period effects on Anopheles gambiae egg hatching. AB - Anopheles gambiae Giles sensu stricto (Diptera: Culicidae) egg development and its relation to environmental parameters is an understudied aspect of vector biology. Although several studies have illustrated the dramatic effects of temperature on egg development, egg hatching dynamics remain unclear. The objective of this study was to expose An. gambiae eggs to various temperatures for different lengths of time and determine the impact on egg development and hatching count. Batches of mosquito eggs (n = 30 eggs/replicate) were incubated under moist conditions at temperatures of 12, 22, 27, 33, and 42 degrees C for intervals of 1, 3, 7, and 10 days. After that, they were flooded with distilled water at 27 degrees C, and hatching counts were observed for up to 7 days. Mosquito eggs held at 22 and 27 degrees C had the highest overall mean hatching count. During early incubation periods, eggs held at 33 degrees C had hatching counts comparable to 22 and 27 degrees C, but counts decreased drastically during later incubation periods. Temperatures of 12 and 42 degrees C reduced mosquito egg viability, because few eggs hatched in these temperature regimes. Other experiments revealed that during early embryonic development, temperature had a major effect on the developing embryo, while later in embryonic development it had no dramatic effect. Microscopic observation of the An. gambiae embryo showed that extreme low and high temperatures affected the normal development of the embryo. A regression model was developed to describe the effect of incubation temperature and incubation period on egg hatching counts, which demonstrated that the optimum temperature for egg hatching ranges from 24 to 30 degrees C, irrespective of incubation period. The interaction between temperature and time period may have implications for dry-season survival and climate-based models of malaria risk. PMID- 17847844 TI - Evaluation of the Mosquito Magnet Pro trap with and without 1-octen-3-ol for collecting Aedes albopictus and other urban mosquitoes. AB - During the summer of 2004, 3 field studies were performed to evaluate the Mosquito Magnet Pro trap with and without 1-octen-3-ol (octenol) in enhancing collections of Aedes albopictus (Skuse). At Field Site 1, 1,501 Ae. albopictus were collected, with 89% collected with octenol. At Field Site 2, 570 Ae. albopictus were collected, with 86% collected with octenol. Aedes albopictus collections were significantly enhanced in both preliminary Field Trials 1 and 2 (P < 0.03). There was a 3-fold increase in collections of Anopheles punctipennis and an 18-fold increase in collections of Ae. vexans at Field Site 2. At Field Site 3, 5,571 were Ae. albopictus, with 75% collected with octenol. Results from the 3rd field trial indicated that Ae. albopictus (P < 0.03), Coquillettida perturbans (P < 0.01), and Ochlerotatus triseriatus (P < 0.03) were significantly more attracted to traps supplemented with octenol than to traps operating without octenol. There was a 2.4-, 6-, and 3.5-fold increase in collections of Ae. albopictus with octenol in Field Trials 1, 2, and 3, respectively. PMID- 17847845 TI - A two-year evaluation of elevated canopy trapping for Culex mosquitoes and West Nile virus in an operational surveillance program in the northeastern United States. AB - The effectiveness of CO2-baited Centers for Disease Control and Prevention miniature light traps elevated in the tree canopy (approximately 7.6 m) was compared with light traps placed at ground level (approximately1.5 m) and grass sod infused gravid traps for collecting Culex pipiens, Culex restuans, and Culex salinarius and detecting West Nile virus (WNV) activity in an operational surveillance program that encompassed 12 ecologically diverse sites in Connecticut in 2004 and 2005. More than twice as many Cx. pipiens were collected on average in light traps suspended in the tree canopy than in either light or gravid traps placed at ground level. This difference was generally restricted to those collection sites where markedly greater numbers of Cx. pipiens were collected with all trapping methods but was not associated with site-specific urbanization indices. Culex restuans was not preferentially attracted to light traps suspended in the tree canopy. No differences in the overall abundance of this species were recorded with either of the 2 trapping procedures, but both light traps were more effective than the gravid traps. Culex salinarius was significantly more attracted to ground-based light traps than traps suspended in the tree canopy, while gravid traps were ineffective at all sites regardless of the level of urbanization or any other specific land-use characteristic. CO2 baited light traps placed in the tree canopy were generally superior to ground based light traps for detecting WNV in Cx. pipiens. West Nile virus-infected females were collected more regularly, and the frequency of infected pools was significantly greater. Twofold higher minimum field infection rates (maximum likelihood estimation [MLE] = 6.7 vs. 3.0 per 1,000 mosquitoes) were also recorded from canopy collections of this species, and virus was detected in canopy-collected females several weeks before it was detected in collections from light traps at ground level. We conclude that the use of CO2-baited light traps placed in the tree canopy for targeted trapping of Cx. pipiens and subsequent detection of WNV are likely to yield better overall results than light traps placed at ground level in this region of the northeastern United States. The virus isolation data obtained from Cx. pipiens collected in gravid traps compared favorably both temporally and spatially with results from canopy trap collections. There were no significant differences in the overall frequency of WNV-infected pools or MLEs for Cx. pipiens, but fewer total WNV isolations were made from Cx. pipiens collected in the gravid traps and virus was detected more infrequently. Results reaffirmed the utility of gravid traps as effective surveillance tools for detection of WNV in Cx. pipiens in the northeastern United States. However, findings also demonstrated that CO2-baited light traps placed in the tree canopy provided more consistent results where weekly detection of virus amplification is a critical objective. The comparative effectiveness of ground- and canopy-based light traps for detection of WNV-infected Cx. restuans and Cx. salinarius was inconclusive owing to the limited number of virus isolations that were made from these species during the 2 years of study. However, WNV virus isolations were made several weeks earlier and more frequently from Cx. restuans collected in traps placed in the canopy rather than at ground level in 2004. Results support the view that ground-based light traps are more effective for detection of WNV in Cx. salinarius. PMID- 17847846 TI - Versatile blood bags for laboratory feeding of mosquitoes. AB - Research programs in mosquito-borne diseases have necessitated the bloodfeeding of mosquitoes in captivity. Parafilm has been shown to be an effective membrane through which mosquitoes can access blood, and numerous feeding devices using parafilm membranes have been reported. However, these devices can be incompatible with experimental conditions, which may require small blood volumes, exact and constant blood temperatures, and inexpensive or disposable materials. We report herein on 2 methodologies that can be used to make parafilm blood bags with a support side and a feeding side made up of a thinner sheet of parafilm. Blood bags were easily and cheaply made to handle volumes as little as 150 microl or as large as 5 ml, to be disposable, and to be easily fastened to a heat source to provide constant and reproducible blood temperatures. Blood bags represent perhaps the most versatile and inexpensive approach to parafilm membrane feeding yet reported. PMID- 17847848 TI - Field trials with tank mixtures of Bacillus thuringiensis subsp. israelensis and Bacillus sphaericus formulations against Culex pipiens larvae in septic tanks in Antalya, Turkey. AB - Efficacy of tank mixtures of commercial Bacillus thuringiensis subsp. israelensis (Bti) and Bacillus sphaericus (Bs) water-dispersable granule (WDG) formulations was evaluated in septic tanks, against Culex pipiens L. (Diptera: Culicidae) larvae. VectoLex WDG (Bs) + VectoBac WDG (Bti) were evaluated at various ratios from 488 g/ha VectoLex + 250 g/ha VectoBac up to 3,000 g/ha of each. All applications and ratios delivering VectoLex WDG at a rate equal to or greater than 988 g/ha provided more than 90% control for 28 days after treatment. The lowest dose provided this level of control for at least 7 days after treatment, with greater than 80% control after 2 wk. These results suggest that a retreatment interval of 2 wk is recommended with the lowest dose and retreatment intervals of 4 or more wk are recommended with the doses equal to or higher than 988 g/ha VectoLex + 250 g/ha VectoBac. PMID- 17847847 TI - Urban habitat evaluation for West Nile virus surveillance in mosquitoes in Albuquerque, New Mexico. AB - As part of an ongoing mosquito surveillance program, 27 sites in the greater metropolitan Albuquerque area (Bernalillo County, New Mexico) were trapped from May through September 2004. Each site was sampled for 1 night weekly, using a standard CO2-baited Centers for Disease Control and Prevention light trap and a gravid trap. Captured mosquitoes were catalogued by location, species, and date, and selected pools were tested for West Nile virus (WNV) by reverse transcription polymerase chain reaction. Based on previous surveillance, WNV was already established in the state of New Mexico. Surveillance during 2003, the 1st year of WNV detection in New Mexico mosquitoes, was focused on the bosque forest of the Rio Grande river valley. Surveillance during summer of 2004 was extended to additional areas around the city of Albuquerque, the state's largest population center. In addition to the standard surveillance objectives, a secondary goal was to determine whether foci of WNV activity were detectable in other habitats besides the riparian ecosystem of the Rio Grande, and in other species not previously identified as vectors. There was no demonstrable advantage to extending the traditional trapping area outside of the Rio Grande valley. Sites in the valley area had WNV-positive mosquitoes earlier in the season, and for a longer period than the added sites. In addition, riparian sites had the highest diversity of species, the largest numbers of Culex spp. captured, and the largest proportion of the WNV-positive mosquito pools from the study. Species found in other areas of the metropolitan area were also represented in the valley. Although WNV activity was detected in other areas of the city, its activity began later and ended earlier than in the river valley. We surmise that the greatest benefit to mosquito surveillance could be achieved by focusing on the river valley area. PMID- 17847849 TI - Prey-predator relationship between the cyclopoids Mesocyclops longisetus and Mesocyclops meridianus with Anopheles aquasalis larvae. AB - Copepods from the genus Mesocyclops are considered predators and potential biological control for mosquito larvae. Two copepod species M. meridianus and M. longisetus were found in natural developmental habitat for malaria vector Anopheles aquasalis in Paria, Venezuela. Predatory potential on 1st-stage mosquito larvae An. aquasalis was evaluated under laboratory conditions for the 2 species of copepod. Further records of both copepod life cycle and body size were taken. A 2 x 3 factorial design was used, consisting of 1:1 and 10:1 prey predator ratios with and without interspecific interactions. Despite significant body-size differences, M. longisetus and M. meridianus reached maturity 17 days after hatching with no significant differences. Life cycle span of both copepod species are described for the first time. The 2 species showed the same predatory potential despite larval (prey) abundance variation. PMID- 17847850 TI - An evaluation of some Trinidadian plant extracts against larvae of Aedes aegypti mosquitoes. AB - In recent times, bioprospecting for plants that show bioactive properties has yielded many chemicals that can be used in controlling mosquitoes. Crude extracts of 4 terrestrial and 3 mangrove plants were assayed against 2-3 larval instars of Aedes aegypti. Among the plants tested, Cordia curassavica showed the highest levels of activity for all the extracts tested. Azadirachta indica showed the least activity, whereas the 2 cultivars of Mangifera indica showed substantial activity for the aqueous extracts. The mangrove species proved to be relatively nontoxic to Ae. aegypti larvae when compared to the terrestrial plants. The results of this study suggest that some common plants in Trinidad may be highly effective in controlling the urban vector of yellow fever and dengue fever, Ae. aegypti. PMID- 17847851 TI - Biotic and abiotic factors affecting Leptolegnia chapmanii infection in Aedes aegypti. AB - The effects of water volume, container surface area and the density of hosts and fungal zoospores on the infectivity of the oomycete fungus Leptolegnia chapmanii to Aedes aegypti were investigated in the laboratory. Late 3rd or early 4th instars from a laboratory colony were used as hosts in all assays. Fourth instars infected with L. chapmanii for 48 h (6.1 +/- 0.2 x 10(4) zoospores/larva) were used as inoculum. Mortality rates were >90% in containers with 20 or fewer larvae when exposed to 1 infected larva, but they decreased to 37% in containers with 60 larvae. Mortality rates varied from 82% to 92% when healthy 4th instars were exposed to 1 and 2 infected larvae, respectively, whereas 100% mortality was obtained with > or =3 infected larvae. Infection and mortality rates in containers with volumes that varied from 300 to 5,000 ml but that had similar water surface area (397 cm2) varied from 89 to 92%, respectively. When water volume was held constant at 250 ml in containers with variable surface areas (14.5-875 cm(2)), larval mortality varied from 96% to 25%, respectively. The ability of L. chapmanii to infect mosquito larvae is dose dependent and influenced by larval density and surface area. PMID- 17847852 TI - Perception and personal protective measures toward mosquito bites by communities in Jaffna District, northern Sri Lanka. AB - Mosquito-borne diseases are of public health importance in war-torn northern Sri Lanka. The severity of mosquito bites and attitudes of the public toward mosquito problems were investigated using a structured questionnaire among communities in 3 administrative divisions in Jaffna District. One hundred fifty-four households were interviewed during this study. Sixty-four percent of the respondents reported that the mosquito problem was severe in their localities. Fifty-two percent stated that mosquito-biting activity was severe in the evening (1500 h 1900 h), 41% at night (after 1900 h), and 7% throughout the day. Severity of mosquito menace was found to have no association with type of house construction. Seventy-seven percent were able to name at least 1 disease transmitted by mosquitoes. Statistical analysis showed no association between education level and public awareness on mosquito-borne diseases. Nearly 88% were able to identify at least a breeding source of mosquitoes and most of them practice measures to eliminate suitable environments for mosquito breeding. Ninety-six percent used personal protective measures against mosquito bites during some seasons or throughout the year. Mosquito coils were the most commonly used personal protective method followed by bed nets. The monthly expenditure for personal protective measures varied from US$0.19 (LKR 20) to US$3.40 (LKR 350). PMID- 17847853 TI - Efficacy studies of Aquaprene (1.8% and 2.8% AI) sand granules and Altosid XR-G (1.5% AI) sand granules against first and second instars of Ochlerotatus taeniorhynchus as a preflood treatment in small field plots. AB - An efficacy study was conducted to evaluate sand granule formulations of Aquaprene (1.8% and 2.8% active ingredient [AI]) and Altosid XR-G (1.5% AI) as a preflood application against Ochlerotatus taeniorhynchus larvae in small field test plots. Aquaprene sand granules (2.8% Al) were applied at 2.5 and 5 lb/acre and the 1.8% AI formulation at 4.2 lb/acre. The 1.8% AI formulation was compared with Altosid XR-G sand granules (1.5% AI) applied at 5 lb/acre. Plots were flooded after 7 days, and 1st and 2nd instars were introduced, pupae were collected, and the plots were drained and dried for 9 days. Assessments were made 21 and 35 days posttreatment. Both Aquaprene sand granules formulations exhibited excellent control throughout the 35-day study. PMID- 17847854 TI - Evaluation of pyrethrin and permethrin ground ultra-low volume applications for adult Culex control in rural and urban environments of the Coachella Valley of California. AB - Six experimental ground ultra-low volume (ULV) applications of Pyrenone 25-5 (0.0025 lb/acre) and Aqua-Reslin (0.007 lb/acre) were made by truck-mounted Pro Mist or London Fog equipment over 1-mi2 study areas in rural and residential environments of the Coachella Valley, Riverside County, California. Efficacy of replicate applications was evaluated by measuring mortality among caged sentinel mosquitoes, by evaluating changes in host-seeking abundance at replicated dry ice baited traps positioned along intersecting east-west and north-south transects, and by differential recapture patterns of marked females released near traps in the sprayed central core and unsprayed control areas. Sentinel mortality agreed well with estimates of droplet density measured by "slide spinners" and was affected by 1) distance of cages from the truck route; 2) landscape features, such as tree lines that created wind shadows; 3) irregular landscape that disrupted the particle cloud; 4) low wind speed that failed to carry the droplet cloud through the environment; and 5) failure of the droplets to penetrate dead airspace within stands of vegetation. Despite variable sentinel mortality, Culex tarsalis relative abundance in rural landscapes within and around our study areas always declined after ULV applications. Concurrent decreases in abundance at traps within sprayed and adjoining unsprayed areas confounded our estimates of percentage of control using Mulla's formula, which compares abundance in sprayed and unsprayed areas pre- and postspray. ULV applications significantly affected recapture patterns, in that recapture rates within the spray zone usually were significantly less than in the unsprayed zone. Collectively, our data indicated that ground ULV applications measurably reduced Cx. tarsalis abundance in rural areas of the Coachella Valley but that further evaluations may be necessary to validate efficacy on Culex quinquefasciatus populations in residential communities. PMID- 17847855 TI - Evaluation of bifenthrin and permethrin as barrier treatments for military tents against mosquitoes in Queensland, Australia. AB - A study comparing the effectiveness of barrier treatment of military tents with bifenthrin and permethrin in preventing entry of mosquitoes was conducted at Wide Bay Training Area, Queensland, Australia. Five military tents were erected at a site in bushland at Mosquito Creek, about 2 km from the coast. Two tents were sprayed with bifenthrin (Bistar 80SC, 0.1% mix, 12.5 ml/liter) and 2 with permethrin (Perigen 500, 1.2%, 24 ml/liter). One was left untreated and served as a control. Carbon dioxide-baited traps were placed inside each tent 0, 2, 4, 6, and 8 wk after treatment, and a single trap was placed in forest 50 m from the tents. The predominant mosquito species collected was Aedes vigilax (78% of collection). Compared to the untreated control, protection against mosquitoes entering treated tents was initially 78.6% for bifenthrin-treated tents and 84.3% for permethrin. At 4 wk, protection was 68.6% for bifenthrin and 50.7% for permethrin. After 6 wk, less than 34% protection was provided by either insecticide. There was no significant difference between the protection provided by either insecticide treatment. The study showed that barrier tent treatments provide a reasonable increase in preventing the entry of mosquitoes for at least 4 wk. PMID- 17847856 TI - Deposition of pyrethrins and piperonyl butoxide following aerial ultra-low volume applications in the Coachella Valley, California. AB - Data on adulticide deposition were collected during studies optimizing aerial ultra-low volume applications and droplet size in the desert environment of the Coachella Valley, Riverside County, California. Pyrenone 25-5 and BVA Spray 13 oil were applied by a single-engine, fixed wing aircraft equipped with 2 Micronair AU5000 atomizers. Data recorded by a portable weather station documented that weather conditions were suitable for application. Adulticide residue was collected using 24-cm-diameter filter papers positioned along 2-3 transects, with 3 positive controls held outside of the treated zone. The trace amounts of 2 major insecticidal components (pyrethrin I and II) and the synergist piperonyl butoxide (PBO) were detected from samples near the center of the spray zone by high-performance liquid chromatography (HPLC); pyrethrin deposition was highest at the center, 156 microg/m2, and it was not detectable 60 m beyond the center of the transect, whereas PBO deposition was 5,000 microg/m2 at the center but was not detectable beyond 150 m. Droplet diameters on spinning Teflon slides were larger than expected for the rated output of the atomizers. For these single swath trials, the lack of swath overlap due to drift resulted in low mortality in sentinel mosquitoes. Detection of residues was limited to the centroid of droplet densities on spinning glass slides and with mortality among sentinel mosquitoes, indicating HPLC may be useful in detecting postspray residues. PMID- 17847857 TI - Efficacy of PermaNet 2.0 against Anopheles culicifacies and Anopheles stephensi, malaria vectors in India. AB - Bioefficacy of PermaNet was evaluated in both the laboratory and field against Anopheles culicifacies and An. stephensi, major malaria vectors in India. Contact bioassays were carried out after repeated washings and ring net bioassays to determine the median knockdown time of mosquitoes. Three villages were selected for the field trial: in the 1st village PermaNets were distributed, in the 2nd village untreated nets were distributed, and the 3rd village was a control. Entomological data were collected using standard procedures. The PermaNet contact bioassays showed high mortality (>80%) even after 20 washes against both the vector species. The median knockdown time of An. culicifacies and An. stephensi was 392 and 480 sec when exposed to fresh PermaNets and 472 and 986 sec when exposed to PermaNets that had been washed 20 times, respectively. PermaNets showed high efficacy in reducing the person-vector contact as evidenced by reduced person-hour density in the PermaNet village. Long-term field trials are indicated to test the impact of use of PermaNets in controlling malaria. PMID- 17847858 TI - Uranotaenia (Pseudoficalbia) mashonaensis, an Afrotropical species found in northern Israel. AB - Uranotaenia (Pseudoficalbia) mashonaensis is recorded from the Jordan Rift Valley of northern Israel based on the collection of adults of both sexes on different occasions. This is the 1st report of this species outside of the Afrotropical region. PMID- 17847859 TI - Presence of Aedes albopictus in Lebanon and Syria. AB - The occurrence of Aedes albopictus in Lebanon and Syria is reported for the first time. Larvae were found in 4 localities in Lebanon, and 1 female was captured inside a house located in a coastal locality in Syria. The potential of the species to vector arboviral disease in the region is noted. PMID- 17847860 TI - Mosquito fauna and arbovirus surveillance in a coastal Mississippi community after Hurricane Katrina. AB - Hurricane Katrina caused massive destruction and flooding along the Gulf Coast in August 2005. We collected mosquitoes and tested them for arboviral infection in a severely hurricane-damaged community to determine species composition and to assess the risk of a mosquito-borne epidemic disease in that community about 6 wk after the landfall of Hurricane Katrina. Light-trap collections yielded 8,215 mosquitoes representing 19 species, while limited gravid-trap collections were not productive. The most abundant mosquito species was Culex nigripalpus, which constituted 73.6% of all specimens. No arboviruses were detected in any of the mosquitoes collected in this survey, which did not support the assertion that human risk for arboviral infection was increased in the coastal community 6 wk after the hurricane. PMID- 17847861 TI - Evidence of laboratory vector competence of Culex modestus for West Nile virus. AB - During the past 10 years, West Nile virus (WNV) has been responsible for large and severe human outbreaks and horse epizootics through the Old and the New World. Since WNV was first isolated from field-collected mosquitoes of Culex modestus in 1964 in France, this species, which aggressively feeds on birds and mammals, is considered a putative WNV vector in Europe. We report on the first evidence on the laboratory vector competence of Cx. modestus for WNV. To assess this trait, F3 and F4 females from southern France were fed through a membrane with a strain of WNV isolated from a horse in the Camargue (Rhone River delta) in 2000. On day 14 after virus ingestion, 90% of mosquitoes displayed a disseminated infection. WNV was detected in the saliva from 2 of 5 infected mosquitoes selected for testing. These preliminary results demonstrate that Cx. modestus is capable of experimentally transmitting WNV. PMID- 17847862 TI - A multiple cage-holding, wind-sensitive vane design for use in ground adulticiding efficacy testing in Harris County, Texas. AB - A wind-sensitive vane apparatus was designed and implemented specifically to accommodate the attachment of otherwise unidirectional insecticide treatment cages used in ground ultra-low volume mosquito adulticide field tests. This cage support system is useful in keeping the potential West Nile virus and St. Louis encephalitis vector Culex quinquefasciatus caged mosquitoes oriented into the wind during field efficacy tests. Testing capacity for resistance surveillance was tripled during the 2005 season, and more reliable results were achieved as a consequence. PMID- 17847863 TI - Graham Prize Address. The William B Graham Prize for Health Services Research acceptance speech delivered June 2, 2007. PMID- 17847864 TI - Improving preparation for senior management in healthcare. AB - Noting the historical and practical relationship of management education in healthcare to business generally, this paper reviews and analyzes four recent criticisms of management education by Pfeffer and Fong, Ghoshal, Mintzberg, and Bennis. It concludes from that analysis that increased effort on assessing and improving healthcare education efforts is essential, and proposes a model for a national program of continuous improvement of educational practice. It reviews existing competency assessment tools in the light of needs, and suggests next steps for educators and practitioners. PMID- 17847865 TI - An analysis of the impact of the David A. Winston Health Policy Fellowship. AB - The objective of the David A. Winston Health Policy Fellowship is to attract and to encourage promising individuals to become successful participants in the health policy process, particularly at the interface of the public and private sectors. From 1987, when the Fellowship was established, through 2004-2005, there have been nineteen Fellows and approximately 65 additional finalists. All but one Fellow hold an MHA or equivalent degree and several hold additional advanced degrees. In comparison to the Fellows, fewer finalists hold additional advanced degrees. The Winston Fellowship Board initiated this study to identify the impact of the Fellowship on the careers of the recipients and, if possible, to track the careers of the finalists to determine the extent to which they have been active in the policy process. The findings are based on a high response rate from former Fellows and a small sample of finalists. Compared to the finalists, the Fellows have been more involved in the policy process and first post-Fellowship employment of Fellows has trended towards Congress in recent years. Fellows noted strengths and weaknesses of the program and made suggestions for improvement. There was agreement among the Fellows that the Fellowship program did influence career direction and content, but it was not possible to draw clear inferences of cause and effect. PMID- 17847866 TI - Innovative teaching for health law: a case study of a hospital medical malpractice lawsuit simulation. AB - In this article we describe a case study of a learning exercise for healthcare management students to more effectively understand how the legal process impacts healthcare organizations and healthcare professionals. Through a semester-long mock trial, we illustrate how healthcare executives can better understand and prepare their employees, their organization, and fellow administrators for the financial, emotional, and time investment that a lawsuit requires. Students participate as a member of the plaintiff team, defendant team, or juror in a simulated lawsuit brought by a patient against a hospital. We explain how students who participate in the simulated lawsuit gain a better understanding of difficult legal principles discussed throughout the course. We further indicate how the mock trial simulation may support achievement of current Commission on Accreditation of Healthcare Management Education (CAMHE) criteria. Next, we highlight how the mock trial allowed students to put into practice many of the health law principles discussed in class through role playing the different stages of medical malpractice trial. The article concludes with examples of how a simulated mock trial may also provide similar interdisciplinary educational, performance improvement, and cost saving benefits to healthcare professionals and their organizations. PMID- 17847867 TI - Healthcare management education 2007: stirring the pot. PMID- 17847868 TI - Patient's page. Bad breath (halitosis) and your oral health-- what you should know.... PMID- 17847869 TI - Oral pathology. Ameloblastoma arising in a dentigerous cyst. PMID- 17847870 TI - Higher performance healing environments. AB - Over the past five years, a remarkable confluence of unprecedented healthcare construction and green building tools and programs tailored for the healthcare sector have created a bold vision of what a 21st Century hospital can be. Informed by the fundamental precept of "first, do no harm", this quiet revolution is shaping the way hospitals and other healthcare facilities are planned, designed, constructed and operated. PMID- 17847871 TI - Site security must evolve with society. AB - Organisations are frequently frustrated by the unbudgeted cost of crime and insecurity but do not necessarily take proactive measures to resolve the problem. Security is rarely viewed as an investment--protection is not as expensive as insecurity, writes Nick van der Bijl, BEM, chairman, National Association for Healthcare Security. PMID- 17847873 TI - Countdown continues to Healthcare Estates. AB - Healthcare Estates is now only two months away, and potential delegates to the IHEEM Conference who would like to take advantage of the early booking discount need to act promptly. Delegates booking before 7 September 2007 will receive a significant saving on places at the IHEEM Conference, which, with its associated exhibition, forms Healthcare Estates (16-17 October 2007 at the Harrogate International Centre). PMID- 17847872 TI - CHES and ASHE build bridges in construction. AB - The Canadian Healthcare Engineering Society (CHES) and the American Society for Healthcare Engineering (ASHE) are partnering with a significant education initiative. They are providing construction and contract personnel with the insights necessary to recognise the inherent risks of progressing healthcare facility projects in patient-occupied buildings, writes Gordon D. Burrill, P. Eng. PMID- 17847874 TI - Trust enhances IT service management. AB - ITIL process adoption may be a prerequisite for the National Programme for IT (NPfIT), but implementation is far from straightforward. IT services company Plan Net has been assisting Barts and The London NHS Trust with implementing its ambitious ITIL processes deployment. PMID- 17847875 TI - Clear policies on mobile phones vital. AB - The potentially illegal photographing of patients is highlighted in new Department of Health guidance on the use of mobile phones in NHS hospitals. Health Estate Journal reports. PMID- 17847876 TI - Ensuring top returns from security budgets. AB - Hospital security must always focus on the need to protect essential healthcare facilities and provide a safe environment for staff and visitors. This can seem like a tall order for organisations struggling to maintain essential public services with finite resources and it is understandable that decisions about security spending can present difficult choices, reports Alex Carmichael, British Security Industry Association technical and membership services director. PMID- 17847877 TI - Colour-coded waste disposal explained. AB - The long-awaited guidance document from the Department of Health is colourful in more ways then one. Health Technical Memorandum (HTM) 07-01: Safe Management of Healthcare Waste was published in December 2006 and replaced the old "purple book" (The Safe Management of Clinical Waste). Was it a sign of things to come that the old guidance had a purple cover, a colour which is now used to indicate cytotoxic and cytostatic wastes? Catalyst Waste Solutions' managing director Nigel Turner explains the new legislation. PMID- 17847878 TI - Sensitive approach to smoking ban. AB - Following the recent ban on smoking in enclosed public spaces, it is in hospitals where the sick, bereaved or emotionally unstable are most likely to find it difficult to abstain, according to the company that provides security services at many NHS hospitals. PMID- 17847879 TI - Cutting carbon use is aim of new service. AB - Dalkia's new CarbonCare service has been designed to help businesses in the battle to reduce carbon emissions. James Verrinder reports from its London launch. PMID- 17847880 TI - Live conductors--attention needed. AB - In some circumstances staff must work near live electrical conductors, and, as the HSE's Wayne Vernon writes, there are detailed regulations that must be adhered to. PMID- 17847881 TI - Processes for reducing NHS carbon footprint. AB - NHS Trust boards face challenging targets for cutting carbon emissions from new and existing facilities. Spirax Sarco's Murdo Macdonald looks at the help available and some of the latest examples of good practice in steam systems for hospital heating and hot water. PMID- 17847882 TI - GP tendering could herald new era of competition for practices. PMID- 17847883 TI - Public health. Smoking battle heats up as age law targets the cool kids. PMID- 17847884 TI - On money and morality. PMID- 17847885 TI - Doctors' leader hails peace--in his own time. Interview by Oliver Evans. PMID- 17847886 TI - Barometer. PCTs August 2007. PMID- 17847887 TI - Turnaround. In from the cold. PMID- 17847888 TI - Finance. Take steps to cut out waste. PMID- 17847889 TI - Communication. Good day for bad news. PMID- 17847890 TI - Victory for NICE as High Court rejects drugs firm complaints. PMID- 17847891 TI - Technology. When will NHS digital dreams become a reality for patients. PMID- 17847892 TI - On drugs in the headlines. PMID- 17847893 TI - Maker of all messages: from media to morale. PMID- 17847894 TI - Data briefing. Conflicting data on choice uptake. PMID- 17847895 TI - Mental health. Born under a bad sign. AB - A Royal College of Midwives survey found 20 per cent of women reported depressive symptoms after childbirth. Fewer than half of all mental health trusts have any kind of perinatal service. NICE proposes managed clinical care networks for each population of 25,000-50,000 live birth a year. PMID- 17847897 TI - Equality. Tools of the trade. PMID- 17847896 TI - Children. A game for two players. PMID- 17847898 TI - No-prep/minimal-prep: the perils of oversimplification. PMID- 17847899 TI - Changing the public's mindset: the "Healthy mouth, healthy practice, healthy lives" initiative. PMID- 17847900 TI - Natural reproduction of the maxillary central incisor: anatomy of a match using a remote laboratory. PMID- 17847901 TI - Implants and the general practitioner. PMID- 17847902 TI - Treatment planning attachments and implants. PMID- 17847903 TI - Implant micro-gap modification. PMID- 17847904 TI - Blending irrigation, canal negotiation, and instrumentation to create ideal endodontic results. PMID- 17847905 TI - AHA 2007 guidelines for the prevention of infective endocarditis: perspectives. PMID- 17847906 TI - The CDx brush biopsy and the diagnosis of oral candidiasis. PMID- 17847907 TI - Semi-processed bite rims for dentures. PMID- 17847908 TI - CEREC and Invisalign: how the technologies complement each other. PMID- 17847909 TI - Computer-generated smile analysis: part 2. PMID- 17847910 TI - Minor tooth movement for crowded mandibular teeth. PMID- 17847911 TI - Is the late Neandertal mandibular sample from Vindija Cave (Croatia) biased? AB - The late Neandertal sample from Vindija (Croatia) has been described as transitional between the earlier Central European Neandertals from Krapina (Croatia) and modern humans. However, the morphological differences indicating this transition may rather be the result of different sex and/or age compositions between the samples. This study tests the hypothesis that the metric differences between the Krapina and Vindija mandibular samples are due to sample bias. Mandibles are the focus of this paper because past studies have posited this region as particularly indicative of the Vindija sample's transitional nature. The results indicate that the metric differences between the Krapina and Vindija mandibular samples are not due to sample bias. This conclusion is consistent with an earlier analysis of sample bias for the Vindija supraorbital sample. PMID- 17847912 TI - Evaluation of the gonial angle in the Anatolian populations: from past to present. AB - Biometrical studies on ancient skeletal series and comparison with modern people by using radiological methods are quite limited in Turkey. Previous studies showed that measurements obtained from orthopantomographs are highly correlated with the actual size of the bones. The aim of the present study is to determine the possible change in gonial angle over time in ancient Anatolian populations with the present. Also an aim was attempted to demonstrate the symmetry of the gonial angle in the jaws and the sexual dimorphism. Gonial angle values (right and left) were taken from 267 Turkish adults with no craniomandibular disorders, orthodontic history or treatment by using panoramic radiographs. Data of the past populations were collected from previous studies. Comparison between right and left sides and the sexual differences were tested by paired student t-test and discriminant analyses were conducted. The results showed that there were no significant differences between the right and left gonial angles of the individuals but there was a significant difference at the left gonial angle between sexes (p < 0.01). Furthermore, no statistically significant difference was found for the gonial angle between the selected past populations with the present sample. PMID- 17847913 TI - Pathology of the mandibles and maxillae from archaeological context: discrepancy between diagnoses obtained by external inspection and radiological analysis. AB - The goal of this research was to investigate the type and frequency of mandibular and maxillary lesions that could not be diagnosed relying solely on external macroscopic observation. The sample comprised of 189 maxillae and 182 mandibles from a late-medieval graveyard. The material was examined both macroscopically and radiologically, using traditional X-ray facilities, orthopantomographs, and a dental X-ray unit. The total number of lesions detected by radiography was 103, with the majority of them (90.3%) showing no external macroscopic features. The most frequently detected diseases were periodontal inflammatory lesions (64.1%), followed by developmental anomalies of the teeth (22.3%). The results of this study revealed that radiography allowed the detection of many underlying pathological lesions of the jaws that otherwise were not detected through external macroscopic examination. PMID- 17847914 TI - Which is the best anthropometric technique to identify obesity: body mass index, waist circumference or waist-hip ratio? AB - This study was designed to define the most suitable anthropometric technique among body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR) as indices of obesity in adult people living in Adana, a Southern province of Turkey. A random sample design was used. A total of 900 individuals (men and non pregnant women aged 25-65 years) were enrolled in the study. Of subjects, 50.9% were females. Anthropometric measurements were performed. Data were analysed using statistical package program. The prevalence of obesity among adults living in Adana was 20.8% 28.4% when defined using BMI, 30.5% by WC and 15.8% 42.0% by WHR. Truncal obesity and gynoid obesity showed similar prevalence with 26.6%, in the same age group. Waist circumference, BMI and WHR identified different proportions of the population, as measured for obesity prevalence. The most common methods for diagnosing overweight and obesity are based on BMI (kg/m2). However, BMI is suboptimal marker for total body fat percentage and even less suitable to assess body fat distribution. WHR is the most useful measure of obesity and the best simple anthropometric index in predicting a wide range of risk factors and related health conditions. PMID- 17847915 TI - Subcutaneous adipose tissue topography (SAT-Top) development in children and young adults. AB - The importance of body composition measurements to elucidate the dynamics of related diseases in pediatrics is gaining recognition. The methods used should not expose subjects to high doses of radiation and require substantial cooperation. The Lipometer is a new optical device that enables the non-invasive, quick and safe determination of the thickness of subcutaneous adipose tissue (SAT) layers (in mm) at any site of the human body. The topographic specification of 15 evenly distributed body sites, which makes it possible to precisely measure subcutaneous body fat distribution, is called subcutaneous adipose tissue topography (SAT-Top). SAT-Top was determined in more than 1000 children and young adults between the ages of 7 and 21. In this paper we describe the SAT-Top development of these subjects through different age groups and the differences between male and female SAT-Top development in each age group. SAT layer profiles (medians of the 15 body sites) for boys and girls in age group 1 (7-9 yrs) show a very similar pattern for both sexes, followed by slightly decreasing SAT layer thicknesses in boys and increasing values in girls in the subsequent age groups. Between age group 3 (11-13 yrs) and age group 7 (19-21 yrs) male and female SAT Top is significantly different. The discriminating power between male and female SAT-Top was investigated by stepwise discriminant analysis, which provided no significant results for age group 1 (7-9 yrs), about 73% correct classification for age group 2 (9-11 yrs) and 3 (11-13 yrs), 83% for age group 4 (13-15 yrs), and about 91-93% for the following age groups (15-21 yrs). It is known that SAT development is the same in both sexes until puberty, when girls gain relatively more fat mass than boys to reach a higher body-fat percentage as adults. This paper presents a precise description of SAT development in boys and girls from childhood to adolescence, which provides a basis for further investigations. PMID- 17847916 TI - Impact of a nutrition intervention program on the growth and nutritional status of Nicaraguan adolescent girls. AB - This research examines the impact of a nutrition education intervention program on the nutritional status and knowledge of Nicaraguan adolescent girls. Anthropometric measurements, hemoglobin values, and data concerning nutritional knowledge were collected from adolescent girls living in Managua, Nicaragua. Using a pre-test/post-test design, data are compared prior to and after the nutrition intervention program. When using Mexican American reference data, statistically significant differences in height-for-age z-scores and weight-for age z-scores were found when comparing the entire sample of baseline data with data collected after three years of the nutrition intervention program (p < 0.05). Significant improvement was also found concerning the indicators of nutritional knowledge (p < 0.05). However, hemoglobin data revealed a significant decrease which may be due to specific environmental factors and pubertal changes. This research has implications concerning the development of successful adolescent focused nutrition intervention programs in Nicaragua, and examines the possibility that catch-up growth occurs during adolescence. PMID- 17847917 TI - Alternative methods of nutritional status assessment in adolescents. AB - The main objective of this cross-sectional study was to determine the validity of the silhouette rating scale and reported values of height and weight in assessing weight status in a group of adolescents. 245 adolescents, students of the Belgrade elementary school, aged 11-14 (12.33 +/- 0.50), were involved. Weight status was assessed by anthropometry, self-reported height and weight and by figure rating scale. From the results obtained significant differences emerged as a function of weight status. The majority of normal weight adolescents were accurate in reporting their body size. The percentage of under-reporters was significantly higher in the overweight/obese group than in the normal weight group (chi2 = 9.741, p = 0.003). The correlation between BMI, both measured and self-reported, and perceived body size was positive and highly significant (p < 0.001). Self-reported weight and height appears acceptable for estimating weight status in normal weight adolescents, but not in those who are overweight or obese. This study also demonstrated that adolescents can estimate with some accuracy their body size using figure ratings scales. PMID- 17847918 TI - Menarcheal onset is associated with body composition parameters but not with socioeconomic status. AB - In the present study the menarcheal status (pre-or postmenarcheal), body composition, weight status, and socioeconomic parameters such as type of school and parental educational level as of 1752 female adolescents ageing between 12 and 18 years (x = 14.6) from rural areas of Eastern Austria were documented. Furthermore the association patterns between body composition, socioeconomic parameters and menarcheal status were analyzed. It turned out, that body composition parameters such as BMI, lean body mass and absolute and relative fat mass were significantly associated with menarcheal status. Postmenarcheal girls were taller and exhibited a higher weight status, a higher absolute and relative amount of fat mass and a higher amount of lean body mass than their premenarcheal counterparts of the same age. In contrast to the significant association between body composition and menarcheal status, no significant impact of educational level on menarcheal status, indicating socioeconomic status could be documented. PMID- 17847919 TI - Influence of some socio-economic factors on growth and development of the boys in the Tuzla region (Bosnia and Herzegovina). AB - The impact of certain exogenous factor (socio-economic, ecological) has been investigated with special attention paid to the parents' living standard, and number of family members on some anthropometric parameters like: body height, body mass, chest circumference, upper leg circumference, upper arm circumference, sitting height, arm length, leg length, pelvis width, shoulders width, lenght of head and with of head on the sample of 698 boys aged 11 to 16 (17) years in the Tuzla region (the northeastern Bosnia, Western Balkan peninsula). Anthropometric measurements have been carried out using methodology proposed by the International Biological program (IBP). The results of these investigations have shown that there is a certain impact of the socio-economic conditions on the growth and development of boys. Children from families that have better living standard are, as a rule, taller, which is indicated by the statistical significant differences (P > 0.01). This trend indicates also value of Body Mass Index (BMI), which is in younger children from the families with lower living standard 16, while in the same category in the children from the families with better living standard it has value 18.5. The real impact of living conditions on the dynamics of development could be the best seen in the period of puberty. The number of children in the family has negative relationship with anthropometric features. Statistically significant differences (P > 0.001) have been detected in numerous analysed features in families with one or two children in comparison with families with three, four, or five children. Therefore, BMI has been significantly lower (16) in children from families with several children, while in the families with one child in the same growth class (11 years) it was significantly higher (17.4). Similar value of BMI (17.9) have children from the families with five children and which are 17 years old. Besides socio-economic conditions, high level of environmental pollution which is typical for Tuzla region for a long time, has also significant impact on the growth and development of children. PMID- 17847920 TI - Nutritional risk screening in hospitalized and haemodialysis patients. AB - Malnutrition is an independent risk factor impacting on higher complications and increased length of hospital stay and costs. The aim of this study was to determine the prevalence of nutritional risk among patients on regular haemodialysis (HD) (Group I, N = 105) and among the patients at Gastroenterology, Endocrinology, Hematology and Clinical Immunology (Group II, N = 652). Cross sectional nutritional evaluation was done using Nottingham Hospital Screening Tool (NS). The prevalence of nutritional risk was 9% in Group I and 21% in Group II (p = 0.0002). We found statistically significant larger quantity of malnourished patients among acute internistic patients than among chronic from the same Group II. Malnutrition among patients on HD didn't differ statistically to chronic internistic patients. We didn't found a significantly higher percentage of nutritional risk among elderly patients (65 years and more). Correlation between body mass index (BMI) and NS was significant, but weak (r = 0.32). We can conclude that the prevalence of nutritional risk among HD patients was lower than we had expected. It seems that the screening tool we used is not sensitive enough for HD patients and needs further investigations. PMID- 17847921 TI - Psycho-social aspects of measures aimed at decreasing prevalence of chronic diseases in the population of returnees in the Osijek Region, Croatia. AB - Recognizing high prevalence of Diabetes mellitus and cardiovascular disorders and low coverage by preventive examinations in the population of returnees, in Osijek Region, we initiated activities for early detection and better managing of chronic diseases. Measures done, were based on public health working methods, such as: education, solidarity and self-responsibility. A special attention was put on psychosocial aspects of the health-related matters. Exactly, free glucose tests were organized with subsequent healthy lifestyles advice session. It was brought to our attention that such intervention should be as much as possible individually oriented, considering many personal and social characteristics of an individual. Gynecological examinations for all women interested in were also organized. On that occasion, women were interviewed in order to get information about their motivation and obstacles for doing preventive examinations and difficulties in adaptation as well. Finally, outcomes of the Project were summarized and put in a larger social context. PMID- 17847922 TI - Examining psychic consequences in firefighters exposed to stress. AB - The total of 178 firefighters from the Littoral Mountainous County, the Republic of Croatia, have undergone psychotestings in three groups--99 professionals from city Rijeka, 44 professionals from suburb and 35 volunteers from suburb. The scores of PSS 10 Cohen Stress Perception Scale, COPE questionnaire, STAI X1 anxiety test as condition and STAI X2 anxiety test as trait personality and Beck Depression Inventory were analyzed. The results have shown that firefighters do not suffer from negative effects of stress. There is slight anxiety as condition in city firefighters and medium anxiety as trait personality in all firemen. All firefighters are often problem-oriented, need only occasionally compassion of environment and sometimes react by avoiding to face stress. They differ significantly by depression (p < 0.001), which is negligible in relation to ordinary population. "Working anxiety", i.e. medium anxiety which is a distinctive trait of their personality becomes the necessary initiator of functioning in the most difficult working conditions. PMID- 17847923 TI - Community based rehabilitation program for people with musculoskeletal conditions. AB - Community based rehabilitation program in people with musculoskeletal conditions was evaluated using Dartmouth COOP Functional Health Assessment Charts/WONCA (COOP/WONCA charts). The program consisted of educative and training protocol in a primary healthcare setting. It had two parts, both with six visits, in the first part three times a week and in the second part once a week. Clients with musculoskeletal conditions (N = 204) were included if they agreed to take active part in the rehabilitation process. The first part of the program was completed by 77 clients, and complete program by 52 subjects. Positive changes on the COOP/WONCA charts were achieved by more than 50% of the subjects that completed the program, in all categories but Social Activities. The program proved effective in terms of short-term evaluation with COOP/WONCA charts in those that complete the program. The high dropout rate and long-term efficiency have yet to be investigated. PMID- 17847924 TI - Self-esteem in children and adolescents differently treated for locomotory trauma. AB - Self-esteem involves the evaluative and affective dimensions of self-concept. It could be influenced by stress situations such as diseases or injuries, especially in the period of puberty and adolescence. The aim of this study was to establish the influence of isolated long tubular bone limbs' fractures in children and adolescents and type of its treatment (conservative or active surgical treatment various techniques) on self-esteem of patients, as well as to establish relationships between self-esteem, depression, anxiety and perception of the social support in the mentioned patients. This prospective clinical trial comprehends 135 patients, 94 male and 41 female, aged 10 to 18, treated for the mentioned fractures in the period from October 2003 until March 2005 in Departments for Pediatric Surgery of three hospitals: the Clinical Hospital Center in Rijeka (88.8% patients), the Clinical Children's Hospital in Zagreb (9.7%), both in Croatia, and 1.5% of the patients in the Clinical Hospital in Mostar (Bosnia and Herzegovina). 53.3% of the patients were treated conservatively, 29.6% of them underwent the elastic stable intramedullary nailing (ESIN), while the remaining 17.1% of the patients were treated with other surgical techniques (AO-plates or Kirschner-wire ostheosyntheses). The basic methods of work were self-reported questionnaires: Rosenberg Self-esteem Scale (RSS), to establish the degree of self-esteem; Children Depression Inventory (CDI), to establish existence and degree of depression; Spielberg State Trait Anxiety Inventory (STAI)-form STAI2, to establish general anxiety; and Test of Perception of Social Support (TPSS). RSS, CDI and STAI2 were administered twice to the patients: at baseline and after 6 months of the trauma, whereas TPSS once, after 1 month of the trauma. Our results point at an decreased self-esteem followed by increased depression and increased general anxiety indicators in all patients within 1 week of experienced trauma, especially in those who underwent the ESIN method, whereas after 6 months of the experienced trauma, self-esteem significantly increased and depression and general anxiety indicators were greatly reduced in all patients. The type of treatment of fractures has no influence on the perception of the social support. Our results suggest that the ESIN method (regardless of its good surgical results and advantages in relation to many other surgical techniques) reduces self-esteem more than conservatively treatment of fractures and AO-plates and K-wire ostheosyntheses. At the same time self-esteem has been recuperated faster in patients treated with ESIN method. Thus, there is no difference in the influence of the type of the treatment of fractures on self-esteem, but in the dynamics of its recuperation in patients according to type of treatment of fractures. Anyway, from a psychological point of view, any type of surgical treatment could be additional stressor, so it should be practiced with criticism and according to the strict surgical indications. PMID- 17847925 TI - Prevalence of periodontal diseases in Zagreb population, Croatia, 14 years ago and today. AB - The aim of this study was to assess prevalence of periodontal diseases within Zagreb adult population in 2000. The sample comprised of 412 examinees of both sexes and all age groups. World Health Organization (WHO) methodology and Community Periodontal Index (CPI), (1997) were used. The data gained was statistically assorted and compared with the data from previously conducted research in 1986. Results showed relatively high prevalence of periodontal diseases. No healthy periodontium was recorded in the 45-and-above age group. Shallow periodontal pockets was registered in 12% of nineteen-year-olds, whereas this symptom was very evident in 45-54 age group (45.7%) and in older than 65 (48.2%). Over 90% of participants had insufficient oral hygiene and 80% required initial periodontal therapy. Approximately 20% needed complex periodontal treatment. Comparison of this data with the previous 1986 research showed improvement of periodontal status in up-to-44 age group due to more healthy persons and more subjects with the initial stages of disease. The possible reason for periodontal health improvement in the last 14 years, evident specially in younger age groups, were the effects of large preventive program measures conducted on schoolchildren in Croatia in 1980-ties and terminated in 1990-ties when the war in Croatia started. Following studies are needed to monitor whether deterioration in oral health will occur regarding to absence of organized preventive programs since 1990-ties. PMID- 17847926 TI - The rational strategies for detecting developmental dysplasia of the hip at the age of 4-6 months old infants: a prospective study. AB - Using ultrasound in evaluation of infant's hip development can reduce surgical procedures, hospitalization and late presentation of developmental dysplasia of the hip (DDH). The increasing incidence of DDH after ultrasound examination is observed and published by many authors. In a prospective study, radiograph of every single ultrasonographic positive hip in infants older than three months, was taken and analyzed in order to see whether it affects infants splintage rate in treating DDH. In a period of 30 months, clinical and simple static ultrasonographic examinations according to Graf were performed on 1430 consecutive infant hips in patients aged between 4 and 6 months. Sonographic positive hips were radiographed and acetabular index (AI) values on simple AP radiographs were analyzed. The sonographic DDH incidence was 51.75 per 1000 hips (51.75 per thousand). After X-ray examination of all 74 ultrasonographic positive hips, only 44 remained abnormal and required treatment indicating a true DDH incidence of 30.77 per 1000 hips (30.77 per thousand). The difference in incidence per ultrasonographic and X-ray positive hips is statistically significant p < 0.01 (t = 5,536). The rational approach in detection of DDH in a child more than 3 months old is to do radiographic assessment of every sonographic positive hip. PMID- 17847927 TI - Epidemiology of pelvic floor disorders between urban and rural female inhabitants. AB - The aim of this study was to investigate the prevalence of pelvic organ prolapse in urban and rural women and to identify possible related factors. They were 1749 participants; one thousand four hundred seventeen (81%) urban women and 332 rural residents (19%). The urban and rural women were congruently regarding to age, parity, using oral contraceptives and postmenopausal status. The urban women were more often obese (p < 0.01), estrogen replacement users (p < 0.001), smokers (p < 0.001), with mild (p < 0.001) and high (p < 0.001) education, and they were often divorced (p < 0.05) than rural women. Rural women were more often alcohol consumers (p < 0.001), with low level of education (p < 0.001) and more often married (p < 0.05) than rural examinees. There were no association between the presence of prolapse and: weight, menopausal status, oral contraceptives and estrogen replacement using, smoking, alcohol consuming and marital status. There were not observed differences in prevalence of prior hysterectomy, urinary incontinence, uroinfectio, sexual and bowel dysfunction between both groups. The prevalence of cystocele, rectocele and uterine prolapse were similar among urban and rural participants. In conclusion, a more complete picture of factors associated with genital prolapse would include in investigation, such as molecular and genetic ones. PMID- 17847928 TI - Laboratory and sonographic findings in dialyzed patients with bilateral chronic knee pain versus dialyzed asymptomatic patients. AB - The aim of this study is to evaluate connection of plasma level of beta2 microglobulin, C-reactive protein and uric acid as well as sonographic parameters like thickness of synovial membrane, thickness of femoral condylar cartilage and presence of joint effusion and Baker's cysts with bilateral knee pain in dialyzed patients, comparing them with parameters in asymptomatic dialyzed patients. Plasma levels of beta2-microglobulin and C-reactive protein were significantly higher in symptomatic patients while uric acid level showed no difference among the groups. In symptomatic patients synovial membrane was thicker and in those patients there were more knee effusions and Baker's cysts. Thickness of femoral condylar cartilage showed no difference between groups. That suggests that inflammatory mechanisms developing from beta2-microglobulin accumulation could be important factor in bilateral knee pain in dialyzed patients even in shorter duration dialysis. PMID- 17847929 TI - Foot morphometric phenomena. AB - Knowledge of the foot morphometry is important for proper foot structure and function. Foot structure as a vital part of human body is important for many reasons. The foot anthropometric and morphology phenomena are analyzed together with hidden biomechanical descriptors in order to fully characterize foot functionality. For Croatian student population the scatter data of the individual foot variables were interpolated by multivariate statistics. Foot morphometric descriptors are influenced by many factors, such as life style, climate, and things of great importance in human society. Dominant descriptors related to fit and comfort are determined by the use 3D foot shape and advanced foot biomechanics. Some practical recommendations and conclusions for medical, sportswear and footwear practice are highlighted. PMID- 17847930 TI - The interleukin-1 receptor antagonist gene and the inhibitor of kappa B-like protein gene polymorphisms are not associated with myocardial infarction in Slovene population with type 2 diabetes. AB - In this study we investigated the association of the interleukin-1 receptor antagonist gene variable number tandem repeat (IL1RN VNTR) polymorphism and of the inhibitor of kappa B-like protein (IKBL) gene polymorphism with myocardial infarction (MI) in a group of patients with type 2 diabetes. The IL1RN VNTR and the IKBL+ 738T > C gene polymorphisms were tested in 374 Caucasians: 151 cases with MI and 223 subjects with no history of coronary artery disease. The IL1RN VNTR polymorphism was not a risk factor for MI in Caucasians with type 2 diabetes (genotype 22 vs. the rest: odds ratio (OR) 1.6; 95% confidence interval (CI) = 0.8-3.5; p = 0.2). We also failed to demonstrate that IKBL+ 738T > C gene polymorphism was associated with MI in patients with type 2 diabetes (OR = 0.9; 95% CI = 0.3-2.6; p = 0.9). We provide evidence that the IL1RN VNTR and the IKBL + 738T > C gene polymorphisms are not risk factors for MI in Caucasians with type 2 diabetes. PMID- 17847931 TI - Chronic patients--persons with diabetes frequent attenders in Croatian family practice. AB - Chronic diseases cause high frequency visits and generate the long-term frequent attenders (FAs). The connection between frequent attendance and specific morbidities in the health care systems in transitional Europe has been underestimated. We investigated whether frequent visits of chronic patients in primary care are related to characteristic of chronic disease (diabetes mellitus) and whether this is influenced by the family practice in the transitional health care. We analyzed the number of visits a day time work for 490 persons with diabetes in the period 1997 to 2000. As the cut-off points between frequent attenders and non frequent attenders (NFAs) we used the value of the third quartile (Q3) of visits determined for the sex and age groups in the parallel study in the whole population. The analysis was performed for 23 variables: demographic characteristics of patients, disease characteristic and variables of physician. Logistic regressions were employed to identify the predictors of FAs/NFAs. 56.9% (in 1997) to 62.4% (in 2000) persons with diabetes were FAs, compared to 22.4% to 24.3% FAs patients in the whole population. Logistic regression analysis significantly differentiated the two group of visits with 68% accuracy. 4 variables are significant predictors for FAs/NFAs: diabetes as the main disease (p = 0.0005), diet-only-treatment (p = 0.0062), treatment by secondary care (p = 0.0116), and if glycated hemoglobin test (HbA1c) is determined (p = 0.0272). Understanding the similarities and differences of FAs/NFAs persons with diabetes may be important in improving the care and management of chronic diseases in family medicine in transitional health care systems. PMID- 17847932 TI - Abnormal systolic blood pressure during treadmill test and brachial artery flow mediated vasodilatation impairment. AB - The aim of the study was to assess the relationship between systolic blood pressure during maximal treadmill test (SBP9mtt)) and flow-mediated vasodilation (FMD). Abnormal rise of SBP(mtt) is the phenomenon more frequent in hypertensive persons but it could be found in normotensive subjects too. 199 subjects referred to treadmill test were enrolled in the study. Four groups were formed: hypertensives with abnormal SBP(mtt) (group A), hypertensives with normal SBP(mtt) (group B), normotensives with abnormal SBP(mtt) (group C) and normotensives with normal SBP(mtt) (group D). Rise of SBP(mtt) above 200 mmHg was considered abnormal reaction. Simple linear regression analysis showed significant inverse relationship between SBP(mtt) and FMD (F = 20.2036, p < 0.001, R2 = 0.0956). Mean FMD index was worst in hypertensive subjects with abnormal SBP(mtt) (group A), followed by normotensives with abnormal SBP(mtt) (group C), hypertensives with normal SBP(mtt) (group B) and the best was in normotensives with normal SBP(mtt) (3.56 +/- 5.17, 4.19 +/- 5.14, 6.81 +/- 8.43 and 10.92 +/- 7.48%, respectively). In multivariate regression analysis FMD showed significant association with abnormal SBP(mtt) (p < 0.001) along with brachial artery diameter (p < 0.001), male gender (p < 0.001), but not with hypertension (p = 0.073), BMI (p = 0.137) and total cholesterol (p = 0.23) (coefficients: -0.26, -0.40, -0.27, -0.13, -0.11 and -0.07, respectively). There was a significant inverse relationship between SBP(mtt) and FMD. An impairment of FMD exists in normotensive subjects with abnormal SBP(mtt). In hypertensives with abnormal SBP(mtt) an additional impairment of FMD exists when compared to hypertensives with normal SBP(mtt). Abnormal SBP(mtt) should be taken into account in global cardiovascular risk assessment. PMID- 17847933 TI - Blood flow multiscale phenomena. AB - The cardiovascular disease is one of most frequent cause deaths in modern society. The objective of this work is analyse the effect of dynamic vascular geometry (curvature, torsion, bifurcation) and pulsatile blood nature on secondary flow, wall shear stress and platelet deposition. The problem was examined as multi-scale physical phenomena using perturbation analysis and numerical modelling. The secondary flow determined as influence pulsatile pressure, vascular tube time-dependent bending and torsion on the main axial flow. Bifurcation and branching phenomena are analysed experimentally through, blood-like fluid pulsatile flow across elastic rubber-like Y-model model. The problem complex geometry near branching in platelet deposit modelling is resolved numerically as Falker-Skan flow. PMID- 17847934 TI - A single-centre experience with octreotide in the treatment of different hypersecretory syndromes in patients with functional gastroenteropancreatic neuroendocrine tumors. AB - The aim of this research was to assess the clinical and biochemical efficacy of the octreotide in the treatment of patients with various functional gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The study included 14 patients treated with octreotide for 6 months. They were diagnosed with VIPoma, glucagonoma, gastrinoma, medullary thyroid carcinoma (solitary and as a part of MEN-II syndrome), pancreatic carcinoids (solitary and as a part of multiple endocrine neoplasia type-1 syndrome-MEN-1 syndrome) and midgut carcinoids. The patients presented with Verner-Morrison, glucagonoma, Zollinger Ellison and carcinoid syndrome respectively. All had a metastatic disease at the time of diagnosis and a positive octreoscan finding. Initially elevated chromogranin A (CgA) levels were detected in 11 (78.6%) and elevated 5-hydroxyindolacetic acid (5-HIAA) levels in 8 (57.1%) patients. Symptomatic efficacy assessments were made by diarrhea reductions during treatment course, and laboratory efficacy was assessed through changes in 5-HIAA and CgA levels. Assessments were made initially and following 6 months of therapy. Median urinary 5-HIAA and the number of stools decreased significantly (p = 0.016 and p = 0.009 respectively, p < 0.05) while CgA levels had the decreasing tendency but not statistically significant (p = 0.14). There was a positive correlation between the 5-HIAA reduction and the decrease in stool number at baseline and during treatment course (p < 0.05). No correlation was observed between 5-HIAA and CgA levels and also there was no correlation between CgA reduction and symptomatic improvement. The results prove octreotide to be effective in reducing symptoms and biochemical markers associated with hypersecretory syndromes of GEP-NETs. PMID- 17847935 TI - Estrogen and progesterone receptor status in primary breast cancer--a study of 11,273 patients from the year 1990 to 2002. AB - The aim of this study was to gain insight of the breast cancer hormone receptor status of our patients, its stratification according to age as well as its changes during the period of 13 years. 11,273 patients with primary breast cancer from several towns in Croatia were included in this study. Patients' tumour specimens were collected from 1990 to 2002 and were analysed on estrogen (ER) and progesterone (PR) receptors in the Laboratory of the Department of Medical Oncology, University Hospital Centre Zagreb. More than half of our breast cancer patients had ER positive tumours (54.3%). We observed ER + tumours increased with age continuously, with highest percentage in the age group of 70 to 79 years (68.1%). Similarly, proportion of PR + tumours was higher in the older age groups, being the highest between 40 and 49 years (55.9%). During 13 years of the study, the increase in frequency and proportion of ER + tumours was observed (from 52% in 1990 to 62% in 2002) and decrease of PR + tumours (56% to 53%). We confirm previous findings that the risk of hormone dependent breast cancer increases with aging. Risk of ER + breast cancer increased for 10% from 1990 to 2002 and PR + tumours decreased for 3.5% in the same period. PMID- 17847936 TI - Antropologic factors in prediction of ovary cancer. AB - The aim of the study was to determine a combination of anthropometric variables that would enable better differentiation between benign and malignant ovarian masses. Prospective study has been performed in a two year period in which 208 women with ovarian lesions were analyzed and correlated with histopathologic surgical findings. We examined the relation between self-reported anthropometric and other variables (height, weight, body mass index--BMI, parity, marital status, education, age, rural versus urban residence, menopausal status) and incidence of ovarian cancer. Age, parity, marital status and menopausal status individually showed statistical significance. PMID- 17847937 TI - Possible prognostic significance of p53 and Ki 67 in inverted sinonasal papilloma. AB - The aim of this study is to test the possible prognostic significance of p53 and Ki67 expression in inverted papilloma of the lateral nasal wall and adjacent sinuses regarding their malignant potential and recurrence. 49 biopsies of the lateral nasal wall and adjacent sinuses obtained from 41 patients from three hospitals were investigated. Immunohistochemically demonstrated p53 and Ki67 expression was measured and statistically evaluated. p53 immunoreactivity was demonstrated in most of papillomas with carcinomas but only in two benign papillomas, while Ki67 demonstrated stronger immunoreactivity in carcinomas and surrounding epithelium. Immunohistochemical staining of inverted sinonasal papillomas for p53 and Ki67 can give useful information concerning the existence of synchronous carcinoma and, in case of high Ki67, a hint toward possible recurrence. PMID- 17847938 TI - Antiproliferative, antiangiogenic and apoptotic effect of photochemotherapy (PUVA) in psoriasis patients. AB - The aim of the study was to investigate the antiproliferative, antiangiogenic and apoptotic effect of photochemotherapy (PUVA) in psoriatic patients, and to compare it with a control group of psoriatics treated with local corticosteroid therapy. The study included 60 psoriasis patients, 30 of them allocated to PUVA therapy and local corticosteroid each. Immunohistochemical methods of staining with Ki-67, F-8 and bcl-2 antibodies were used to determine proliferative keratinocyte count, to visualize the number of blood vessels in the dermis, and to determine the number of cells exhibiting expression of the antiapoptotic oncoprotein bcl-2, respectively. In all study patients, the values of Ki-67, F-8, bcl-2 and PUVA score were recorded pre- and at six weeks post-therapeutically. Study results showed a statistically significant decrease in the epidermal proliferative keratinocyte count and dermal number of blood vessels after both therapeutic modalities (p < 0.001 both). The value of bcl-2 showed a statistically significant increase in the group of patients treated with PUVA therapy (p = 0.001) and an increase in the control group, demonstrating enhanced keratinocyte apoptosis after treatment. Accordingly, study results demonstrated the antiproliferative, antiangiogenic and apoptotic effect of both PUVA and local corticosteroids. These very mechanisms appear to play a key role in the action of most antipsoriatic therapies. PMID- 17847939 TI - Progression of optic neuritis to multiple sclerosis in the County of Split Dalmatia, Croatia. AB - The aim of this study was to determine the incidence of monosymptomatic optic neuritis (MON) and progression of MON to multiple sclerosis (MS) from the Mediterranean region of southern Europe in the County of Split-Dalmatia, Croatia during the 11 years period from 1991 to 2001. This study was made retrospectively on the 87 cases (59 female, aged 25.9 +/- 11.3 and 28 male aged 29.9 +/- 9.2) of MON, which were treated at the Department of Ophthalmology and Department of Neurology, Split, University Hospital, from January 1991 to December 2001. In each case the diagnosis was confirmed by a chart review and cases were ascribed to the data of admittance at hospital. The annual incidence of MON was 1.9 per 100,000 (95% CI, 0.4-3.5). The incidence among males was 1.2 (95% CI, 0-2.9) cases / 100,000 per year and 2.5 (95% CI, 0.1-4.9) among females. A significant seasonal variations in the incidence of MON was not found (chi2 = 6.81, p = 0.08). MS developed in 20 of 87 patients (22.9%) and median time was 25 (SE 8) months, (95% CI, 9-41) after the MON onset. After two years 12.6% of patients with MON developed MS, 20.6% after 5 years and 22.9% after 10 years. MS was slightly but not significantly more frequent in women than in men (chi2 = 0.72, p = 0.3). In conclusion, the progression of MON to MS in the County of Split Dalmatia, Croatia was at a relatively moderate frequency. PMID- 17847940 TI - Intercostal catheter analgesia is more efficient vs. intercostal nerve blockade for post-thoracotomy pain relief. AB - A pain after thoracotomy may result in a postoperative hypoventilation and lead to atelectases and pneumonia. This study was aimed to compare two analgesic regimens after posterolateral thoracotomy. 80 patients (40-70 years) undergoing thoracotomy were randomized to intercostal catheter analgesia (group A, n = 40) and intercostal nerve block (group B, n = 40). Patients in group A were given 20 mL of 0.5% bupivacaine injections twice a day by intercostal catheter. Intercostal nerve blockade was performed using 5 mL of 0.5% bupivacaine. Intercostal nerve in thoracotomy wound, nerves below and above thoracotomy wound was also injected. PaO2, PaCO2, FVC, FEV1 and visual analog pain scale (VAS) were obtained preoperatively, 24, 48 and 72 hours after operation. Postoperative complications were recorded at the patient discharge. Differences between groups were calculated using Mann-Whitney, KW test and chi square test. The arterial blood gas analyses did not show statistically significant change in any group and time according to the baseline values. FVC and FEV1 decreased significantly in both groups at first postoperative day according to baseline measurements. Patients in B group had significantly higher FEV1 values in the third postoperative day (73.05 +/- 11.25 in A vs. 83.50 +/- 9.17 in B group, p < 0.05). Intercostal catheter analgesia resulted in significantly lower postoperative VAS scores and reduced opioid requirement as compared to intercostal nerve blockade. No differences in the postoperative complications were observed between groups. PMID- 17847941 TI - MR assessment of bile duct size in healthy individuals: comparison with US measurements. AB - The purpose of the study was to determine the difference in extrahepatic bile duct (EBD) size measured by magnetic resonance (MR) compared with those measured by ultrasound (US). Changes of EBD size related to aging were analyzed too. Size of EBD was measured in 76 randomly selected healthy individuals. Three radiologists blinded to the result of other study preformed measurements by US and three different T2 weighted MR sequences. Correlation and linear regression analysis of obtained data were performed. The mean diameter of EBD measured by US was 3.17 mm and by MR was 3.14 mm on thick slab rapid acquisition with relaxation enhancement (TSE), 3.26 mm on thin section single-shot TSE (HASTE) and 3.30 mm on coronal fully rewound gradient echo (True FISP). There was no statistical difference between US and different MR sequences (p < 0.05). A trend of increase of EBD with age (0.0155 mm per year, p = 0.0954) was observed. Size of EBD highly correlated for each MR sequence with US measurement validating use of MR as a reliable method for evaluation of EBD size. This conclusion is stressed by increase of EBD size with age demonstrated by all measuring methods. PMID- 17847942 TI - Dental anxiety in relation to emotional and behavioral problems in Croatian adolescents. AB - The investigation was performed on 113 adolescents in the age between 15 and 18 years (63 boys, 50 girls). Corah Dental Anxiety Scale (CDAS) and Children's Fear Survey Schedule - Dental Subscale (CFSS-DS) were used for evaluation of dental fear and Child Medical Fear Questionnaire (CMFQ) for evaluation of the fear of medical treatment. Achenbach Youth Self Report questionnaire (YSR) was used for evaluation of emotional and behavioral problems. The tests were filled in by children. The aim of the study was to evaluate the level of dental anxiety in adolescents and to assess a cause--consequence relationship between dental anxiety and emotional and behavioral problems in adolescents. The results of CDAS, CFSS-DS and CMFQ tests showed that dental anxiety scores and the total internalizing problems were higher in girls. Girls displayed more physical problems (p < 0.001) and were more prone to anxiety/depression disorders (p < 0.05). Both boys and girls were more aggressive, more prone to delinquent behaviour and had more externalizing problems in comparison with the average values obtained for the Croatian population. Significant correlation coefficients for boys were calculated for age and anxiety/depression, and delinquent behaviour and aggression (p < 0.05). Significant correlations were observed between physical problems and dental anxiety measured by the CFSS-DS test (p < 0.01), and between physical problems and the total internalizing problems (p < 0.05). In girls, the CMFQ scores showed significant correlations between dental anxiety and physical problems (p < 0.05), and anxiety/ depression (p < 0.01) and the total internalizing and externalizing problems (p < 0.05). Significant correlations were calculated for age and the total internalizing and externalizing problems for boys (p < 0.05). According to the results of both CDAS and CMFQ tests, anxiety in girls showed significant correlations with delinquent behaviour (p < 0.01). CDAS scores for girls showed significant correlations with aggression (p < 0.05) and the total externalizing problems (p < 0.01). PMID- 17847943 TI - Predictive calculation of effectiveness of a regional bone marrow donor registry in Vojvodina, Serbia. AB - The aim of this study was to determine the percentages of patients from Vojvodina who would find at least one HLA identical unrelated donor in various sizes of donor files. To determine the probability that 200 patients will have given phenotype, we defined three-locus haplotype frequencies through the phenotype frequencies of HLA A,B and DR antigens as well as observed AB and BDR haplotype frequencies. Then we calculated the percentages of patients theoretically able to have at least one HLA identical donor in a donor file of a certain size. According to the results of a study sample, predictive estimation of the effectiveness of regional bone marrow donor registry in Vojvodina, would be 14% with 5,000 donors, 23% with 10,000 donors, 38.5% with 20,000 donors, 49.5% with 30,000 donors and 76% with 100,000 donors in the registry. The appropriate size of registered donor file that would give at least one HLA identical donor for more than 45% of patients from Vojvodina is 30,000 donors. PMID- 17847944 TI - Combined influences of gradual changes in room temperature and light around dusk and dawn on circadian rhythms of core temperature, urinary 6-hydroxymelatonin sulfate and waking sensation just after rising. AB - The present experiment aimed at knowing how a gradual changes of room temperature (T(a)) and light in the evening and early morning could influence circadian rhythms of core temperature (T(core)), skin temperatures, urinary 6 hydroxymelatonin sulfate and waking sensation just after rising in humans. Two kinds of room environment were provided for each participant: 1) Constant room temperature (T(a)) of 27 degrees C over the 24 h and LD-rectangular light change with abrupt decreasing from 3,000 lx to 100 lx at 1800, abrupt increasing from 0 lx to 3,000 lx at 0700. 2) Cyclic changes of T(a) and with gradual decrease from 3,000 lx to 100 lx onset at 1700 (twilight period about 2 h), with gradual increasing from 0 lx to 3,000 lx onset at 0500 (about 2 h). Main results are summarized as follows: 1) Circadian rhythms of nadir in the core temperature (T(core)) significantly advanced earlier under the influence of gradual changes of T(a) and light than no gradual changes of T(a) and light. 2) Nocturnal fall of T(core) and morning rise of T(core) were greater and quicker, respectively, under the influence of gradual changes of T(a) and light than no gradual changes of T(a) and light. 3) Urinary 6-hydroxymelatonin sulfate during nocturnal sleep was significantly greater under the influence of gradual changes of T(a) and light. 4) Waking sensation just after rising was significantly better under the influence of gradual changes of T(a) and light. We discussed these findings in terms of circadian and thermoregulatory physiology. PMID- 17847945 TI - Perceptions of family medicine and career choice among first year medical students: a cross-sectional survey in a Turkish medical school. AB - Public attitudes to family medicine in Turkey have lagged behind its rapid academic development. The effect of undergraduate training in primary care on medical students' attitudes to family medicine has not been assessed. Objectives of this study were to assess the attitudes of first year medical students at Uludag University School of Medicine in Bursa, Turkey to family medicine and to determine their career aspirations. The study was a survey of the first year medical class in 2003-2004. The response rate was 95% (248/261 students). Students were positive about their choice of medicine as a career but had negative opinions of general practice. Female students were more positive in this respect. Initial preference was for specialization in fields other than general practice with little knowledge of the academic specialty of family medicine. Greater undergraduate exposure to family medicine is needed in order to increase knowledge of the field and influence student career choices. PMID- 17847946 TI - Fieldwork: man in the system of nature and priority of natural laws in human life. AB - Fieldwork is a branch of inseparable unity of natural and humanitarian sciences; it is aimed at the cultural origin of humanity on the maximum level of its variety. Practically all natural sciences have some space determined by ethnic conscience in nature cognition: ethnodemography, ethnobotany, ethnozoology, etc. Fieldwork guides the research of human culture from the laws of nature. This kind of knowledge is useful to balance human relations with nature and avoid conflicts. Peoples should exchange their wisdom in the dialogue with nature to be more safe. Fieldwork understood as traditional culture only, explaining the variety of ethnoses on our earth, is just the narrow and diachronic level of this branch of knowledge. The cosmological knowledge, where fantasy and not exhausted in its cognition understanding the world of nature are mixed, forms the source of fieldwork and in many respects explains the direction of knowledge: the man finds himself under the open sky, he is the child of nature. Then as time went on there appeared a gradual transition--first nature was creating the man, then by and by he began turning to answer nature by his activity. Nowadays the man is actively creating nature. There are two levels of fieldwork: the ancient one which deals with the origin of ethnoses and the modern one which explores how contemporary life is determined by ethnic specific traits. Fieldwork is the core of multidisciplinary situation in man's knowledge. It is related to such humanitarian sciences: semiotics, culturology, sociology, history, philosophy, literature, linguistics. In the cycle of natural sciences fieldwork stands close to anthropology, geography, biology, demography. Fieldwork as a science has the two main levels--the "sophy" level and the logos "level". The first one discovers wisdom of human life, the second one is aimed at logical structuring of knowledge, here proceed various classifications of peoples. PMID- 17847947 TI - Differencies in morphologic characteristics between top level gymnasts of year 1933 and 2000. AB - In 1933, at the 5th Regional Sokol Meeting in Ljubljana which was at the time a place in the Yugoslav Kingdom, Skerlj carried out the first measurements of 189 gymnasts, active competitors; in 2000, at the World Cup Meeting in Ljubljana, Cuk and associates carried out measurements of 40 top gymnasts. Our analysis of identical variables has shown that there is no difference in body height and weight of the gymnasts in 1933 and those in 2000, while there is a significant difference in the width of their shoulders and pelvis, the contemporary athletes being wider in their shoulders and narrower in their pelvis. The differences can be assigned to the new requirements in contemporary gymnastics as exercises are becoming more difficult, including more rotation around the vertical and horizontal axis. PMID- 17847948 TI - Erdheim-Chester disease and concomitant tuberculosis successfully treated with chemotherapy and long-term steroids. AB - Erdheim-Chester disease (ECD) is a rare histiocytosis usually affecting the skeletal system, but visceral organs and central nervous system involvement are common as well. Probability exists that immunomodulatory therapies and disorders can play a role in clinical course of the disease. Because of rarity of the disorder, it is hard to classify it and standardize the treatment options, but, according to published material and our experience, cytotoxic chemotherapy and long-term steroids have therapeutic benefit. Although this approach can probably be accepted as standard of care management, novel therapeutic modalities should be explored, and pathogenesis and disorder classification should be cleared out as well. The case of ECD affecting skeletal system and lungs and concomitant laryngeal tuberculosis successfully treated with chemotherapy and long-term steroid therapy is presented. PMID- 17847949 TI - Propane-associated autoerotic asphyxiation: accident or suicide? AB - Autoerotic fatalities refer to a death resulting from the participation in a sex related activity designed to heighten sexual arousal. The overwhelming majority of these deaths are due to asphyxia, most often by hanging or ligature compression of the neck. Here we report a case of "atypical" autoerotic fatality in which death was not induced by ligature compression. Unusual death of a 24 year-old man, involving propane inhalation and plastic bag suffocation, is described. The special characteristics of propane gas as an asphyxiant agent are discussed, as well as its effect on the human body. PMID- 17847950 TI - Pulmonary embolism caused by a migrated gunshot projectile. AB - Pulmonary embolism caused by a foreign body is an exceedingly rare event. We report on a 62 year old woman who suffered a gun shot injury to her left knee with concomitant vascular lacerations. The bullet migrated through the venous system into the pulmonary circulation causing a pulmonary embolism. The projectile remained stationary for ten years. Taking into consideration that she is virtually asymptomatic and that regular follow up examinations showed no further migration of the foreign body, we opted for a conservative venue of management. PMID- 17847951 TI - Ovarian cancer: PCD and brain metastases. AB - Paraneoplastic cerebellar degeneration (PCD), the one of the most common paraneoplastic syndromes, refer to clinical disorders associated mostly with lung, ovarian and breast cancer, but not directly caused by the cancer or its metastases. Pathologic finding is an extensive loss of Purkinje cells in the cerebellum. Immunohistochemically, the auto-antibodies on the Purkinje cells had been detected. Clinically, PCD is characterized by sub-acutely evolving pancerebellar symptoms. Neurological dysfunction may appear before the detection of the underlying cancer. Therefore, the surgical exploration is necessary for the final diagnosis. The patient undergoes specific therapy. Soon, neurological status of the patient gets irreparable worse. Death come usually 2-3 years after the first symptoms of the PCD occurs. Case of a 63-years old woman with PCD as the first evidence of her cancer is reported. The patient developed brain metastases and died almost 3 years after the first symptoms of PCD occur PMID- 17847952 TI - Coexistence of ochronosis and B 27 positive ankylosing spondylitis. AB - We describe a 49-year-old man with coexistence of ochronosis and B27 positive ankylosing spondylitis. This is the first report documenting the simultaneous occurrence of ochronosis and B27 positive ankylosing spondylitis, with no positive familiar history for seronegative spondylarthropathies. The relations of these rheumatic diseases are discussed. PMID- 17847953 TI - Parental grief in three societies: networks and religion as social supports in mourning. AB - How do people respond to the grief of parents over the death of their infant child? This article documents the experience of one of the authors, an American married to a Russian whose child died in England. Responses to this death by friends, colleagues and family in the USA, England, and two cities in Russia varied considerably in terms of depth and degree of engagement (emotional engagement, respect, or distance and avoidance). What factors underlie these varied responses? Two are identified, one structural, the other cultural: the strength of the social ties within social networks, and religiosity as historically sedimented within a culture. The degree of engagement is correlated with network form; but the content of engagement depends on religiosity. PMID- 17847954 TI - General beliefs about the world as defensive mechanisms against death anxiety. AB - Death ideation and death anxiety represent the cognitive and affective dimensions of death attitudes, respectively. General beliefs about the world are proposed to be useful defensive mechanisms protecting persons against the death anxiety provoked by death ideation. SEM is employed to test the proposed mediation model, using a sample of 133 Hong Kong Chinese university students. Results showed that death ideation was significantly and inversely linked to belief in social cynicism, reward for application, and fate control. Moreover, higher levels of belief in fate control and lower levels of religiosity predicted greater death anxiety. Only belief in fate control partially mediated the relationship between death ideation and death anxiety. Discussion focused on how social axioms serve as useful defensive mechanisms against death anxiety. PMID- 17847955 TI - Introducing the 3-A grief intervention model for dementia caregivers: acknowledge, assess and assist. AB - With our aging population, it is estimated that in the near future there will be an overwhelming increase in the number of individuals dealing with Alzheimer's disease or a related dementia (ADRD). From the time that symptoms begin to insidiously emerge, it can take well over ten years for the disease to run its course. In addition to the crippling effect for those inflicted, this lengthy duration can have an ongoing debilitating effect on the family members who are grieving while providing care. Researchers have claimed that the manner in which family members experience and manage their grief reactions to the pre-death losses can influence both caregiving outcomes and adjustment to bereavement once those with the disease have died. Given the relevance of grief management, this article provides answers to such questions as: How do family caregivers of individuals with ADRD manifest their grief? How can healthcare professionals intervene in assisting with grief management? The answers are provided introducing the 3-A grief intervention model for family caregivers of individuals with ADRD. The 3-A model enfranchises the caregiver grief experience through Acknowledging, Assessing, and Assisting in grief management. In doing so, different grieving styles are identified and the role that denial and respite plays in adapting to the family caregiver's grief experience is recognized. Clinical strategies to assist in grief management are also provided. PMID- 17847956 TI - Parents in death-related literature for children. AB - This article explores ways in which parents are represented as being involved with children in death and loss experiences. These representations are taken from 46 selected examples of death-related literature designed to be read by or with children. The main goal for us is to ask how parents are portrayed in these books and how their interactions with children are depicted. Since parents usually bear primary responsibility for the care of their children, they are ordinarily expected to share their experience and insights with their children, and to help children cope with death and loss. What do they do and how do they help (or not help) children in this body of literature? PMID- 17847957 TI - A cross-cultural comparison of death anxiety: a brief note. AB - Data are reported from samples of undergraduates around the world who have been administered Templer's Death Anxiety Scale. Data from 24 American samples and from 16 nations were identified. Strong sex differences were found and an association between the scores of men and women. PMID- 17847958 TI - Leaders claim bullies thrive and middle managers are left to fail. PMID- 17847959 TI - PCTs ignoring orders on patient group involvement. PMID- 17847960 TI - Hewitt details accountability push. PMID- 17847961 TI - Winning over NHS staff could be Brown's first big challenge. PMID- 17847962 TI - The cost of a day's work. PMID- 17847963 TI - Leadership. Managers must dig deep for new skill set. PMID- 17847964 TI - Barometer. Public health June 2007. PMID- 17847965 TI - Leadership. In the minds of managers. PMID- 17847966 TI - Work for workforce. AB - The Leitch Review of Skills has helped to raise the profile of improved skills overall for the future prosperity of the UK economy. Health organisations need to see a clearer business case to invest in Skills for Health tools. More emphasis on labour market intelligence will help provide clarity to employers. PMID- 17847967 TI - Skills agreement. Recipe for success. AB - The aims of the national health Sector Skills Agreement need regional and local implementation by stakeholders to become reality. Work in the East of England will produce a first regional skills agreement later this year. The Harlow Project is producing award winning process on recuitment and retention. PMID- 17847968 TI - Competences. Made for the job. PMID- 17847969 TI - Education. The kids are alright. AB - Diplomas will provide an alternative to GCSEs and A-Levels, although pupils will be able to combine the different qualifications. The Society, Health and Development diplomas will include elements on numeracy, literacy and technology common to all diplomas as well as sector-specific content developed by employers through sector skills councils. Work replecement will be more flexible. PMID- 17847970 TI - Commissioning. A potent remedy. PMID- 17847971 TI - Patient needs. Someone to squeeze. PMID- 17847972 TI - DoH misses deadline as it fails to deliver own turnaround plan. PMID- 17847973 TI - Foundation trusts. Deferrals and delays applications target at risk. PMID- 17847974 TI - Criminal checks fail to exclude staff. PMID- 17847975 TI - Health inequalities. Why minorities still stand out from the primary care crowd. PMID- 17847976 TI - On getting safety on board. PMID- 17847977 TI - Public health. Early learning is key weapon in obesity war. PMID- 17847978 TI - Data briefing. Inconsistency in admissions coding. PMID- 17847979 TI - Turnaround. Tales from the edge. PMID- 17847980 TI - Care farming. Exploring the new 'farmacy'. PMID- 17847981 TI - Mental health initiative. Out of the shadows. PMID- 17847982 TI - Perspectives of husbands of women with breast cancer: impact and response. AB - When breast cancer is diagnosed, it has the potential to have an impact on a woman's partner and influence how the male partner can support the woman. This qualitative study was undertaken to explore the impact on male partners of having a wife who has been diagnosed with breast cancer. In-depth interviews with 15 husbands provided a rich sense of the nature of the impact and how these men responded to it. Analysis revealed two overarching themes: (1) the diagnosis was shocking and unexpected, and (2) the impact of breast cancer on the male partner is wide-ranging. The respondents described a wide range of changes that had occurred in their lives since the unexpected, shocking diagnosis. They shared vivid accounts of personal emotional reactions, changes in daily work life and household responsibilities, worries about children, and changes in their relationships with their wives. They experienced ongoing struggles to balance the demands within their lives. Two significant challenges these men described were coping with work-related demands and sorting out how to be supportive to their wives. Clearly, the breast cancer diagnosis had an impact on these men and created personal tension for them. Cancer nurses need to be aware of this impact, acknowledge the sense of vulnerability it can create in male partners, and work to find effective ways to support them. PMID- 17847983 TI - Perspectives of husbands of women with breast cancer: information needs. AB - The majority of women, when diagnosed with breast cancer, turn to their partners for support. However, the diagnosis and treatment of this disease will have an impact on the partner as well and could influence his ability to be supportive. This study was undertaken to explore the perceived informational needs of male partners of women diagnosed with breast cancer. The in-depth interviews provide a rich description about the nature of men's informational needs in a context of upheaval and unexpected events. The 15 husbands in this study described information as important in their capacity to manage the situation. Three overarching themes were identified: the men had questions and concerns throughout the time period since the diagnosis, lack of information created difficulties for them, and health care professionals could be helpful. These men struggled to find relevant information and to sort out what was applicable to their own situation. They found little information specifically directed to partners. Assessment by cancer nurses ought to include the male partner's needs for information and his capacity to process information throughout the cancer experience. PMID- 17847984 TI - Evaluation of "The Many Faces of Pain": a chronic cancer pain management education program. AB - A descriptive, correlational design was used to evaluate the effectiveness of a chronic cancer pain management education program. The Nurses' Knowledge and Attitude Survey Regarding Pain (NKAS) was used to evaluate the program. A convenience sample of 27 registered nurses was recruited to participate in the study. Analysis of the data revealed a significant difference between pre-test and post-test scores on the NKAS. There were no significant correlations observed between any study variables. The small convenience sample prevents the ability to generalize the findings. It is concluded that the education program was effective in improving knowledge and attitudes related to chronic cancer pain management. Implications for nursing practice, research, education, and administration are suggested. PMID- 17847985 TI - Evaluation of an educational program for the caregivers of persons diagnosed with a malignant glioma. AB - BACKGROUND: Caring for a loved one with a malignant glioma can be a formidable responsibility. The guarded prognosis, side effects of treatments, and changes in brain function, personality and behaviour pose unique challenges in care provision by family members. It is rare that institutions provide educational programs for caregivers. PURPOSE: To evaluate the impact of providing information in an educational program to caregivers of patients diagnosed with a malignant glioma. METHODS: A structured educational program for caregivers of brain tumour patients was developed based upon multidisciplinary expert opinion and caregiver feedback. Twenty-four caregiver participants were enrolled in the program. Knowledge was assessed before, immediately following, and four to six weeks following the program. Open-ended questions were used to explore the caregivers' experiences, as well as additional benefits derived from the program. RESULTS: Knowledge scores on testing immediately after the program and four to six weeks following the program were statistically significantly improved from baseline testing, although there was a decline in scores four to six weeks after the program. These findings demonstrate effective knowledge transfer (recall of the information) immediately after the education program and four to six weeks later. Specific qualitative and quantitative data serve as a basis for understanding caregivers' needs and experiences. PMID- 17847986 TI - Information needs of adolescents when a mother is diagnosed with breast cancer. AB - This pilot study was undertaken to increase our understanding of the information needs of adolescents when a mother is diagnosed with breast cancer. In-depth interviews with 13 adolescents provided insight into the types of questions they had at the time of their mother's diagnosis and how satisfied they were with the access they had to information. These adolescents had many questions about cancer and its treatment, specific questions about their mother's disease and survival, and concerns about their own risk. Each sought information on their own in addition to conversations with one or both parents. They identified their most pressing concern as the need to know about their mother's survival. All felt it was important to have access to information and to have someone with whom they could talk about what was happening. This person needed to be someone with whom they were comfortable and whom, in turn, had both credibility and comfort with emotions. Clearly, adolescents experience needs for information when their mother is diagnosed with breast cancer. Cancer nurses can assist women diagnosed with breast cancer plan how to support their adolescent children and meet the needs for information. PMID- 17847988 TI - Research mentorship--who needs it? PMID- 17847987 TI - "The worst experience": The experience of grandparents who have a grandchild with cancer. AB - This study explored the experience of eight grandparents having a grandchild diagnosed with cancer. Semi-structured interviews, both with individuals and couples, were used to gain a better understanding of the meaning these grandparents give to this experience. A thematic analysis based on Giorgi's (1997) phenomenological method highlighted three central themes: "Living the worst experience", "Having to support: A crucial role for grandparents", "To feel supported to better carry on." The results of this study can contribute to enhancing the quality of care for grandparents affected by their grandchild's cancer. PMID- 17847989 TI - Not "simply" teaching another chemotherapy patient...part II. PMID- 17847990 TI - [Human factor]. PMID- 17847991 TI - [Aging personnel in nursing--challenge for leadership: learning from other branches]. PMID- 17847992 TI - [Center for optimized wound management in Hamburg: seeing the whole person]. PMID- 17847993 TI - [Interdisciplinary consultation of nursing experts in delayed wound healing--1: Problem oriented use of specialty competence]. PMID- 17847994 TI - [Promoting physical activity in nursing: recognizing and using the health potentials of patients]. PMID- 17847995 TI - [Problems from general practice--solutions for general practice: preventing needlestick injuries]. PMID- 17847996 TI - [Transportation of ventilated patients: are you increasing the risk of ventilator associated pneumonias?]. PMID- 17847997 TI - [Disease managemenet in type II diabetes mellitus: improving primary care]. PMID- 17847998 TI - [Applying expert standards for prevention of falls in clinical routine: adapting to structures and processes]. PMID- 17847999 TI - [Falls of residents and patients: no liability for general frailty]. PMID- 17848000 TI - [Nursing care responsibilities in the neonatal department: continuous monitoring in the foreground]. PMID- 17848001 TI - [Human images in nursing:--5: Human image in economics: utilitarianism as the guiding principle]. PMID- 17848002 TI - [Step by step for nursing care competence--4: Feeding: also attending to pleasure]. PMID- 17848003 TI - [From case to case: as you treat me, so I treat you--or?]. PMID- 17848004 TI - [Recognizing and understanding illnesses: exhaustion as the main complaint]. PMID- 17848005 TI - Integrating nutrition into holistic nursing practice. PMID- 17848006 TI - Healing our cultural eating disorders. PMID- 17848007 TI - Nutrition as protection for the busy person. PMID- 17848008 TI - Nutritional self-care. PMID- 17848009 TI - Nutrient-rich sea vegetables. PMID- 17848010 TI - The secret of the black seed: an ancient healing remedy for the modern healer. PMID- 17848011 TI - Holistic nurses as part of the obesity solution. PMID- 17848012 TI - Learning about herbs. PMID- 17848013 TI - Holistic healing from obesity: one holistic nurse's journey. PMID- 17848014 TI - 38 flower essences for self-healing. PMID- 17848015 TI - Gingerbread: a guided imagery. PMID- 17848016 TI - Homeopathy as a nursing intervention. PMID- 17848017 TI - What it costs to implement a plan: plan-level and task-level contributions to switch costs. AB - Four experiments were conducted to identify the costs of implementing a plan in the task span procedure, which requires subjects to retrieve the task to perform on the current target from a list of planned tasks in memory. Experiment 1 compared switch costs in the task span procedure with switch costs in the explicit task-cuing procedure, which presented cues indicating the task to perform on each target. Switch costs were greater in the task span procedure. Experiments 2-4 were designed to identify the sources of this difference. Experiment 2 showed that the requirement of establishing a correspondence between the list of task names and the list of targets contributed to switch costs. Experiment 3 showed that retaining lists of similar task names produced greater switch costs than did retaining lists of dissimilar task names. Experiment 4 showed that memory load had no effect on switch costs. The results are discussed in terms of the interaction between plan-level and task-level processing in the implementation of plans. PMID- 17848018 TI - The influence of overlapping response sets on task inhibition. AB - The aim of the present study was to examine the contribution of overlapping response sets to the occurrence of task inhibition, measured as n-2 task repetition cost. We had subjects switch among four tasks. Three tasks overlapped on both stimulus set and response set. A fourth, neutral, univalent task never overlapped on the stimulus set but, across three experiments, varied in terms of the degree of overlap in the response set. We found that overlap in response set affects task inhibition. We suggest that response set overlap increases the competition among tasks and, thus, triggers task inhibition to resolve this competition. PMID- 17848019 TI - The roles of encoding, retrieval, and awareness in change detection. AB - In the experiment reported here, we examined the processes by which expected (probable) changes are detected more frequently than are unexpected (improbable) changes (the change probability effect; Beck, Angelone, & Levin, 2004). The change probability effect may be caused by a bias toward probable changes during encoding of the prechange aspect, during retrieval of the prechange aspect, or during activation of an explicit response to the change. Participants performed a change detection task for probable and improbable changes while their eye movements were tracked. Change detection performance was superior for probable changes, but long-term memory performance was equivalent for both probable and improbable changes. Therefore, although both probable and improbable prechange aspects were encoded, probable prechange aspects were more likely to be retrieved during change detection. Implicit change detection was also greater for probable changes than for improbable changes, suggesting that the change probability effect is the result of a bias during the retrieval and comparison stage of change detection. The stimuli used in the change detection task may be downloaded from www.psychonomic.org/archive. PMID- 17848021 TI - Memory decreases for prose, but not for poetry. AB - Memory for details of text generally declines relatively rapidly, whereas memory for propositional and context-based meanings is generally more resilient over time. In the present study, we investigated short-term memory for two kinds of verbal material: prose and poetry. Participants heard or read prose stories or poems in which aphrase near the start of the passage served as a target. The text continued, and after various delays, memory was tested with a repetition of the target (old verbatim; O), a paraphrased lure (P), or a lure in which the meaning was changed. For prose, memory for surface details (as measured by O/P discrimination) declined over time (Experiments 2-4), as was expected. For poetry, memory for surface details (O/P discrimination) did not decline with increasing delay (Experiments 1, 3, and 4). This lack of decline in memory for the surface details of poetry is discussed in relation to similar results previously observed for musical excerpts (Dowling, Tillmann, & Ayers, 2001), suggesting that a particular role is played by the temporal organization and rhythmic structure of poetry andmusic. PMID- 17848020 TI - Direct evidence for a role of working memory in the attentional blink. AB - Theories of selective attention often have a central memory component, which is commonly thought to be limited in some way and is thereby a potential bottleneck in the attentional process. There have been only a few attempts to validate this assertion, and they have produced mixed results. This study presents a specific examination of the link between working memory and attention by engaging active rather than passive memory operations. Two experiments are reported that provide evidence for the involvement of working memory in the attentional blink (AB) phenomenon. Memory loads of increasing size had a detrimental effect on attentional performance within the blink-sensitive interval, but not beyond. Speeded response requirements proved to modulate the AB, but were independent from the memory load effect. Theoretical implications for current models of selective attention are discussed. PMID- 17848022 TI - Suppression effects on musical and verbal memory. AB - Three experiments contrasted the effects of articulatory suppression on recognition memory for musical and verbal sequences. In Experiment 1, a standard/comparison task was employed, with digit or note sequences presented visually or auditorily while participants remained silent or produced intermittent verbal suppression (saying "the") or musical suppression (singing "la"). Both suppression types decreased performance by equivalent amounts, as compared with no suppression. Recognition accuracy was lower during suppression for visually presented digits than during that for auditorily presented digits (consistent with phonological loop predictions), whereas accuracy was equivalent for visually presented notes and auditory tones. When visual interference filled the retention interval in Experiment 2, performance with visually presented notes but not digits was impaired. Experiment 3 forced participants to translate visually presented music sequences by presenting comparison sequences auditorily. Suppression effects for visually presented music resembled those for digits only when the recognition task required sensory translation of cues. PMID- 17848023 TI - Cultural scripts guide recall of intensely positive life events. AB - In four studies, we examined the temporal distribution of positive and negative memories of momentous life events. College students and middle-aged adults reported events occurring from the ages of 8 to 18 years in which they had felt especially good or especially bad about themselves. Distributions of positive memories showed a marked peak at ages 17 and 18. In contrast, distributions of negative memories were relatively flat. These patterns were consistent for males and females and for younger and older adults. Content analyses indicated that a substantial proportion of positive memories from late adolescence described culturally prescribed landmark events surrounding the major life transition from high school to college. When the participants were asked for recollections from life periods that lack obvious age-linked milestone events, age distributions of positive and negative memories were similar. The results support and extend Berntsen and Rubin's (2004) conclusion that cultural expectations, or life scripts, organize recall of positive, but not negative, events. PMID- 17848024 TI - The effect of divided attention on false memory depends on how memory is tested. AB - In three experiments, we investigated the effects of divided attention on false memory, using the Deese/Roediger-McDermott (DRM) paradigm. In Experiments 1 and 2, participants studied six DRM lists with full attention and six in one of two divided-attention conditions (random number generation or digit monitoring). Both divided-attention conditions increased false recall of related words (Experiment 1) but reduced false recognition (Experiment 2). These results were confirmed in Experiment 3, in which the type of secondary task was manipulated within groups. We argue that the increase in false recall with divided attention reflects a change in participants' response criterion, whereas the decrease in false recognition occurs because the secondary tasks prevent participants from generating associates of the words presented at study. PMID- 17848025 TI - The negative cascade of incongruent generative study-test processing in memory and metacomprehension. AB - Previous research suggests that when participants engage in generative study activities, the processing of text is enhanced and improvements in memory and metacomprehension result. However, few studies have investigated the influence of processes required by the testing situation or the interaction between encoding and retrieval processes on metacomprehension accuracy. The present experiments examine whether the congruency of processes generated during study and required at retrieval affect memory, metacomprehension, and control processes. Study orientation and test type were congruent (i.e., letter-reinsertion: detailed test), incongruent (i.e., letter-reinsertion: conceptual test), or neutral (i.e., read: conceptual test). After generative study, but before testing, participants made metacomprehension predictions for previously studied texts. Controlled strategy selection was measured in Experiment 2. When processes at study and test were congruent, cued recall performance and metacomprehension predictions were more accurate than when study and test were incongruent. For incongruent conditions, metacomprehension predictions were no better than chance; thus, controlled strategy selection was based on inaccurate metacomprehension, thereby further penalizing memory performance relative to congruent conditions. These findings extend a transfer-appropriate processing framework to metacomprehension. PMID- 17848026 TI - Strength-based mirror effects in item and associative recognition: evidence for within-list criterion changes. AB - Strength-based mirror effects occur when the hit rate is higher and the false alarm rate is lower following strongly encoded study lists than when following more weakly encoded study lists. In Experiments 1A and 1B, strength-based mirror effects were observed in separate tests of single item and associative recognition for random word pairs. In Experiment 2, strength-based mirror effects were again seen when item and associative recognition were tested together. Finally, in Experiments 3 and 4, opposing strength-based mirror effects were observed for item and associative recognition when individual words and word pairs were presented at different rates in the same study lists. Strength-based mirror effects could result from participants' adopting a more conservative decision criterion following strong lists than following weak ones. If this is the case for both item and associative recognition, the present results demonstrate that subjects can adopt different response criteria for different recognition tasks and can alternate between them on a trial-by-trial basis. PMID- 17848027 TI - Memory for general and specific value information in younger and older adults: measuring the limits of strategic control. AB - The ability to selectively remember important information is a critical function of memory. Although previous research has suggested that older adults are impaired in a variety of episodic memory tasks, recent work has demonstrated that older adults can selectively remember high-value information. In the present research, we examined how younger and older adults selectively remembered words with various assigned numeric point values, to see whether younger adults could remember more specific value information than could older adults. Both groups were equally good at recalling point values when recalling the range of high value words, but younger adults outperformed older adults when recalling specific values. Although older adults were more likely to recognize negative value words, both groups exhibited control by not recalling negative value information. The findings suggest that although both groups retain high-value information, older adults rely more on gist-based encoding and retrieval operations, whereas younger adults are able to remember specific numeric value information. PMID- 17848028 TI - Incubation benefits only after people have been misdirected. AB - Incubation refers to the popular idea that stopping work on a problem may, at times, be a more efficient means by which to reach a solution than continuing to work. Empirical studies of incubation have used few participants and have provided ambiguous and discrepant results. We investigated three potential accounts of incubation in retrieval and search problems (subconscious work, spreading activation, and fixation forgetting) with the help of a large Internet based participant pool. The amount of time allotted for explicit work on each of 12 problems was controlled, while the distribution of that time was manipulated in several incubation conditions. When problems were presented by themselves, none of the incubation conditions aided in the solution of either anagram or remote associate test problems. However, incubation benefits arose when participants were given misdirecting clues (probably because time delays facilitated forgetting of these clues). PMID- 17848029 TI - Visual similarity effects on short-term memory for order: the case of verbally labeled pictorial stimuli. AB - Four experiments examined the effect of visual similarity on immediate memory for order. Experiments 1 and 2 used easily nameable line drawings. Following a sequential presentation in either silent or suppression conditions, participants were presented with the drawings in a new, random order and were required to remember their original serial position. In Experiment 3, participants first learned to associate a verbal label with an abstract matrix pattern. Then they completed an immediate memory task in which they had to name the matrices aloud during presentation. At recall, the task required remembering either the order of the matrices or the order of their names. In Experiment 4, participants learned to associate nonword labels with schematic line drawings of faces; the phonemic similarity of the verbal labels was also manipulated. All four experiments indicate that the representations supporting performance comprise both verbal and visual features. The results are consistent with a multiattribute encoding view. PMID- 17848030 TI - Age-related differences in immediate serial recall: dissociating chunk formation and capacity. AB - We assessed the contribution of two hypothesized mechanisms to impaired memory performance of older adults in an immediate serial recall task: decreased temporary information storage in a capacity-limited mechanism, such as the focus of attention, and a deficit in binding together different components into cohesive chunks. Using a method in which paired associations between words were taught at varying levels to allow an identification of multiword chunks (Cowan, Chen, & Rouder, 2004), we found that older adults recalled considerably fewer chunks and, on average, smaller chunks than did young adults. Their performance was fairly well simulated by dividing attention in younger adults, unlike what has been found for long-term associative learning. Paired-associate knowledge may be used in an implicit manner in serial recall, given that younger adults under divided attention and older adults use it well despite the relatively small chunk capacities displayed by these groups. PMID- 17848031 TI - Visual working memory for global, object, and part-based information. AB - We investigated visual working memory for novel objects and parts of novel objects. After a delay period, participants showed strikingly more accurate performance recognizing a single whole object than the parts of that object. This bias to remember whole objects, rather than parts, persisted even when the division between parts was clearly defined and the parts were disconnected from each other so that, in order to remember the single whole object, the participants needed to mentally combine the parts. In addition, the bias was confirmed when the parts were divided by color. These experiments indicated that holistic perceptual-grouping biases are automatically used to organize storage in visual working memory. In addition, our results suggested that the bias was impervious to top-down consciously directed control, because when task demands were manipulated through instruction and catch trials, the participants still recognized whole objects more quickly and more accurately than their parts. This bias persisted even when the whole objects were novel and the parts were familiar. We propose that visual working memory representations depend primarily on the global configural properties of whole objects, rather than part-based representations, even when the parts themselves can be clearly perceived as individual objects. This global configural bias beneficially reduces memory load on a capacity-limited system operating in a complex visual environment, because fewer distinct items must be remembered. PMID- 17848032 TI - Cognitive adaptations arising from nonnative experience of sign language in hearing adults. AB - Three experiments examined spatial transformation abilities in hearing people who acquired sign language in early adulthood. The performance of the nonnative hearing signers was compared with that of hearing people with no knowledge of sign language. The two groups were matched for age and gender. Using an adapted Corsi blocks paradigm, the experimental task simulated spatial relations in sign discourse but offered no opportunity for linguistic coding. Experiment 1 showed that the hearing signers performed significantly better than the nonsigners on a task that entailed 180 degree rotation, which is the canonical spatial relationship in sign language discourse. Experiment 2 found that the signers did not show the typical costs associated with processing rotated stimuli, and Experiment 3 ruled out the possibility that their advantage relied on seen hand movements. We conclude that sign language experience, even when acquired in adulthood by hearing people, can give rise to adaptations in cognitive processes associated with the manipulation of visuospatial information. PMID- 17848033 TI - Diminutives facilitate word segmentation in natural speech: cross-linguistic evidence. AB - Final-syllable invariance is characteristic of diminutives (e.g., doggie), which are a pervasive feature of the child-directed speech registers of many languages. Invariance in word endings has been shown to facilitate word segmentation (Kempe, Brooks, & Gillis, 2005) in an incidental-learning paradigm in which synthesized Dutch pseudonouns were used. To broaden the cross-linguistic evidence for this invariance effect and to increase its ecological validity, adult English speakers (n=276) were exposed to naturally spoken Dutch or Russian pseudonouns presented in sentence contexts. A forced choice test was given to assess target recognition, with foils comprising unfamiliar syllable combinations in Experiments 1 and 2 and syllable combinations straddling word boundaries in Experiment 3. A control group (n=210) received the recognition test with no prior exposure to targets. Recognition performance improved with increasing final syllable rhyme invariance, with larger increases for the experimental group. This confirms that word ending invariance is a valid segmentation cue in artificial, as well as naturalistic, speech and that diminutives may aid segmentation in a number of languages. PMID- 17848034 TI - Cognitive implications of facilitating echoic persistence. AB - Seventeen participants performed a tone-pattern-matching task at different presentation levels while concurrently engaged in a simulated-driving task. Presentation levels of 60, 65, and 70 dBC (SPL) were combined factorially with tone-matching delays of 2, 3, and 4 sec. Intensity had no effect on performance in single-task conditions and short-delay conditions. However, when the participants were engaged concurrently in the driving task, a significant interaction between presentation level and delay was observed. In the longest delay condition, the participants performed the tone-pattern-matching task more efficiently (more quickly and without additional errors) as presentation intensity increased. These findings demonstrate the interaction between sensory and cognitive processes and point to a direct-intensity relationship where intensity affects the persistence of echoic memory. Implications for facilitating auditory processing and improving auditory interfaces in complex systems (i.e., transportation environments), particularly for older and hearing-impaired listeners, are discussed. PMID- 17848035 TI - Equivalent inter- and intramodality long-term priming: evidence for a common lexicon for words seen and words heard. AB - Weaker inter- than intramodality long-term priming of words has promoted two hypotheses: (1) separate visual and auditory lexicons and (2) modality dependence of implicit memory. In five experiments, we employed manipulations aimed to minimize study-test asymmetries between the two priming conditions. Activities at visual and auditory study were matched, words were phonologically consistent, and study modality was manipulated between subjects. Equal magnitudes of inter- and intramodality priming were found in experiments with visual and auditory stem completion at test, with visual fragment completion at test, and with visual and auditory perceptual identification at test. A within-subjects experiment yielded the conventional intramodality advantage. The results point to a single amodal lexicon and to modality-independent phonological processing as the basis of implicit word memory. PMID- 17848036 TI - Coreference and lexical repetition: mechanisms of discourse integration. AB - The use of repeated expressions to establish coreference allows an investigation of the relationship between basic processes of word recognition and higher level language processes that involve the integration of information into a discourse model. In two experiments on reading, we used eye tracking and event-related potentials to examine whether repeated expressions that are coreferential within a local discourse context show the kind of repetition priming that is shown in lists of words. In both experiments, the effects of lexical repetition were modulated by the effects of local discourse context that arose from manipulations of the linguistic prominence of the antecedent of a coreferentially repeated name. These results are interpreted within the context of discourse prominence theory, which suggests that processes of coreferential interpretation interact with basic mechanisms of memory integration during the construction of a model of discourse. PMID- 17848038 TI - Stress is popular again. PMID- 17848037 TI - Sources of error in picture naming under time pressure. AB - We used a deadline procedure to investigate how time pressure may influence the processes involved in picture naming. The deadline exaggerated errors found under naming without deadline. There were also category differences in performance between living and nonliving things and, in particular, for animals versus fruit and vegetables. The majority of errors were visuallyand semantically related to the target (e. celery-asparagus), and there was a greater proportion of these errors made to living things. Importantly, there were also more visual-semantic errors to animals than to fruit and vegetables. In addition, there were a smaller number of pure semantic errors (e.g., nut-bolt), which were made predominantly to nonliving things. The different kinds of error were correlated with different variables. Overall, visual-semantic errors were associated with visual complexity and visual similarity, whereas pure semantic errors were associated with imageability and age of acquisition. However, for animals, visual-semantic errors were associated with visual complexity, whereas for fruit and vegetables they were associated with visual similarity. We discuss these findings in terms of theories of category-specific semantic impairment and models of picture naming. PMID- 17848039 TI - Lithium: underappreciated and underused? AB - Lithium is a remarkable drug with a fascinating history. Although less popular than other anticonvulsant and atypical antipsychotic mood-stabilizing drugs, lithium is beneficial in bipolar disorder and may be superior to other drugs for treatment-resistant depression and for reducing suicidal behaviors. Various studies have demonstrated that lithium has neuroprotective and neurotrophic cellular effects in the brain, suggesting it may be "brain healthy" for patients with mood disorders and useful for patients with other neurodegenerative disorders. In this article, I describe the history of lithium and review important aspects of its clinical use. PMID- 17848040 TI - Living with Tourette's syndrome. AB - Illnesses in children are difficult enough, but for children and adolescents with Tourette's syndrome, the emergence of unwelcome motor and vocal tics in social situations can lead to not only embarrassment, but also increased self consciousness, social isolation, thoughts of persecution, and physical pain. This article offers an overview of Tourette's syndrome and focuses on DSM-IV-TR criteria, severity, prevalence and course, etiology and epidemiology, indications for medications, psychosocial therapies, and nursing implications. PMID- 17848041 TI - Psychosocial issues in end-of life care. AB - Interest in aging and dying has increased substantially, in large part because of recent biomedical advances, the shift from a sacred to a secular conception of death, and the death awareness movement. The importance of mental health professionals in helping people through the aging and dying process is now more widely recognized. In addition, because societies are becoming increasingly multicultural, a greater need exists for appreciation of the cultural aspects involved. This article discusses the various psychosocial factors involved in aging and dying. It also touches on cultural factors that mental health and nursing professionals should be aware of to remain in tune with the changing times and better serve their patients. PMID- 17848042 TI - Fatigue and sleep quality in nurses. AB - Fatigue is a critical issue for nurses that may lead to medical errors, degradation in performance, decreased mental acuity, and social problems. Poor sleep quality is also a contributing factor in fatigue that nurses experience. Therefore, the purpose of this study was to examine the differences in perceptions of fatigue between night-shift and day-shift nurses, as measured by scores on the Brief Fatigue Inventory (BFI) and to examine differences in sleep quality between the two groups, as measured by responses on the Pittsburgh Sleep Quality Index (PSQI). Univariate analysis of variance showed significant differences between the two groups on the BFI, with the night-shift cohort reporting higher mean scores on the BFI. Significant differences were also found between the two groups on PSQI mean scores, with the night-shift cohort reporting higher mean scores. Findings from this study suggest that night-shift nurses, compared with day-shift nurses, perceived a much higher level of fatigue and had poorer sleep quality. Further research is needed to evaluate interventions that might decrease fatigue in nurses and improve their sleep quality. PMID- 17848043 TI - Clinical and psychosocial significance of trauma history in the treatment of schizophrenia. AB - Research has suggested that many individuals with schizophrenia have been exposed to significant trauma, not only after but also prior to the onset of illness. This article reviews the literature suggesting that exposure to certain kinds of trauma, including childhood sexual abuse, may increase the risk of developing schizophrenia. It also presents data from across studies that suggest a history of trauma may affect the course and symptom presentation of the disorder, resulting in higher levels of psychosocial dysfunction and higher levels of anxiety and hallucinations. An individual example is presented, and implications for case conceptualization, assessment, and treatment are discussed. PMID- 17848044 TI - Odontology or philologic: medical disputation about the teeth. AB - The dissertation, here rendered, was published at the gymnasium of Hof in 1669. It is remarkable that the respondent, who was probably also its author, declared in the title page that he intends to do his task "following the custom of the blessed Hebrews and any other conventions of true Israelites" and cites in the following text repeated proverbs of Rabbis. Therefore, we suppose him to have been a Jew converted to the Christian faith. His Odontology is a large collection of knowledge about the teeth, the etymology of this term, the question of them belonging to the bones, their anatomy and fixation in the jaws, and their tasks in the crushing of foods and helping in pronunciation, and in animals for self protection. With respect to their removal, he emphasizes that one read Sennert's Institutiones Medicae. The points of view discussed by the author depended more heavily on philological than on medical authors. Nevertheless, there are mentioned also "paramedical" opinions of the general population. The monograph seems to us important for the history of dentistry. PMID- 17848045 TI - Lorenz Heister and oral disease with the original text from his papers. AB - Lorenz Heister (1683-1758) was the major academic surgeon of the eighteenth century. He served as an army surgeon in a number of campaigns and eventually became the professor of anatomy and surgery at Altdorf University. In 1739, he published a comprehensive book on surgery that became the standard text on the subject. It was widely reprinted and translated into many languages. The English version was the first systematic treatise on surgery to appear in that language. The book has many chapters devoted to diseases of the mouth and their treatment. PMID- 17848046 TI - Dental postcards no. XXXVII. A man who believes in, supports, and attends the dental societies versus one who does not! PMID- 17848047 TI - Dentistry on stamps. George Leslie MacKay. PMID- 17848048 TI - Forsyth, Harvard, and endodontic education: 1970-1987. AB - In 1970, there were few fully-educated endodontists and formalized endodontic programs in the United States. Dr. Alvin Krakow began a teaching/clinical program that combined the best in technical education and research for academically minded young clinicians. The Forsyth Dental Center hosted the program while the Harvard University School of Dental Medicine (HSDM) offered the prerequisite courses in basic science. The program ended in 1987 and was reinstituted in 1993. Today, the program continues to graduate a small group of diversified and educated clinicians. A number of graduates in the original group have made significant contributions to the specialty. This historical perspective focuses on the early years of the combined program. PMID- 17848049 TI - Theodore Roosevelt's "presidential smile" and questionable dental health. AB - Theodore ("TR" or "Teddy") Roosevelt (1858-1919), who served as the twenty-sixth President of the United States from 1901 to 1909, was an "Icon of the American Century." Characterized by immense energy, numerous skills, zest for life, and enduring accomplishments, he made an impressive ascent to political importance. However, he also experienced serious, chronic, oral and systemic health problems. In spite of these significant health obstacles, he chose "the strenuous life," and cultivated a lifetime of joy, laughter and humor. TR was known as "the first president that smiled," and he was typically photographed and illustrated grinning from ear to ear. His flashing white teeth, wide smile, and engaging openness became welcome symbols of national and international acceptance. When Roosevelt died, suddenly and prematurely at the age of 60, dentists and physicians of that time began to investigate the probable medical causes of his untimely demise. The "focal infection hysteria" of the early 1900s convinced some of these health professionals that "a bad tooth", that previously had been endodontically treated, was the probable cause of death. Much of the early 20th century evidence-supporting the notion that oral sepsis was a "cause" of local or systemic disease-has now been proven, on closer inspection, to be anecdotal or of questionable scientific merit. Nevertheless, during those early days, it was common practice to extract all endodontically or periodontally involved teeth to eliminate any possible foci of infection that many clinicians believed could cause disease. PMID- 17848050 TI - 19th century dentistry advertising trade cards. Merchant's gargling oil. A Liniment of man & beast. Circa 1890. PMID- 17848051 TI - A lingering mystery on the Cape. Why did it take so long to arrest a suspected killer? PMID- 17848052 TI - Family matters. PMID- 17848053 TI - And now, the hard part. That sweet little thing is about to commandeer your life. Be prepared. PMID- 17848054 TI - Finding what works. PMID- 17848056 TI - Pump up the family. PMID- 17848055 TI - A peaceful adolescence. PMID- 17848057 TI - When cultures clash. PMID- 17848058 TI - Introduction: conceptualizing and partitioning the emergence process of zoonotic viruses from wildlife to humans. AB - This introduction provides a telegraphic overview of the processes of zoonotic viral emergence, the intricacies of host-virus interactions, and the distinct role of biological transitions and modifying factors. The process of emergence is conceptualized as two transition stages which are common and required for all disease emergence, (1) human contact with the infectious agent and (2) cross species transmission of the agent, and two transition stages which are not required for emergence and appear unavailable to many zoonotic pathogens, (3) sustained human-to-human transmission and (4) genetic adaptation to the human host. The latter two transitions are presumably prerequisites for the pandemic emergence of a pathogen. The themes introduced herein are amplified and explored in detail by the contributors to this volume. Each author explores the mechanisms and unique circumstances by which evolution, biology, history, and current context have contrived to drive the emergence of different zoonotic agents by a series of related events; although recognizable similarities exist among the events leading to emergence the details and circumstances are never repetitive. PMID- 17848059 TI - Infectious disease modeling and the dynamics of transmission. AB - The dynamics of any infectious disease are heavily dependent on the rate of transmission from infectious to susceptible hosts. In many disease models, this rate is captured in a single compound parameter, the probability of transmission P. However, closer examination reveals how beta can be further decomposed into a number of biologically relevant variables, including contact rates among individuals and the probability that contact events actually result in disease transmission. We start by introducing some of the basic concepts underlying the different approaches to modeling disease transmission and by laying out why a more detailed understanding of the variables involved is usually desirable. We then describe how parameter estimates of these variables can be derived from empirical data, drawing primarily from the existing literature on human diseases. Finally, we discuss how these concepts and approaches may be applied to the study of pathogen transmission in wildlife diseases. In particular, we highlight recent technical innovations that could help to overcome some the logistical challenges commonly associated with empirical disease research in wild populations. PMID- 17848060 TI - The evolutionary genetics of viral emergence. AB - Despite the wealth of data describing the ecological factors that underpin viral emergence, little is known about the evolutionary processes that allow viruses to jump species barriers and establish productive infections in new hosts. Understanding the evolutionary basis to virus emergence is therefore a key research goal and many of the debates in this area can be considered within the rigorous theoretical framework established by evolutionary genetics. In particular, the respective roles played by natural selection and genetic drift in shaping genetic diversity are also of fundamental importance for understanding the nature of viral emergence. Herein, we discuss whether there are evolutionary rules to viral emergence, and especially whether certain types of virus, or those that infect a particular type of host species, are more likely to emerge than others. We stress the complex interplay between rates of viral evolution and the ability to recognize cell receptors from phylogenetically divergent host species. We also emphasize the current lack of convincing data as to whether viral emergence requires adaptation to the new host species during the early stages of infection, or whether it is largely a chance process involving the transmission of a viral strain with the necessary genetic characteristics. PMID- 17848061 TI - Influenza viruses in animal wildlife populations. AB - Influenza viruses belong to the family Orthomyxoviridae. Genus Influenza A viruses are true zoonotic agents with many animal reservoirs, whereas genus Influenza B viruses are generally considered to be a virus of humans. The genome of influenza A viruses consists of eight unique segments of single-stranded RNA of negative polarity; they are typed according to their surface proteins, hemagglutinin (HA) and neuraminidase (NA). HA and NA, the major antigenic determinants of influenza A viruses, are present in 16 and nine serologic subtypes, respectively. Annual epidemics and occasional pandemics of influenza in humans depend on the continued evolution of influenza viruses. Although they have numerous potential host populations, most of our genetic and biologic data are obtained from studies of domestic populations of species such as chickens, turkeys, swine, and horses. Concerning wildlife populations, including wild populations of these domesticated species, much less is known. The purpose of this review is to establish what role wildlife populations play in the continued evolution of influenza viruses. Future work needs to determine what chain of events makes it possible for an influenza virus to be successfully transmitted to, and more importantly within, an alternative host population. Even questions as fundamental as which hosts can transmit viruses to humans remain unanswered so far. PMID- 17848062 TI - Overviews of pathogen emergence: which pathogens emerge, when and why? AB - An emerging pathogen has been defined as the causative agent of an infectious disease whose incidence is increasing following its appearance in a new host population or whose incidence is increasing in an existing population as a result of long-term changes in its underlying epidemiology (Woolhouse and Dye 2001). Although we appear to be in a period where novel diseases are appearing and old diseases are spreading at an unprecedented rate, disease emergence per se is not a new phenomenon. It is almost certain that disease emergence is a routine event in the evolutionary ecology of pathogens, and part of a ubiquitous response of pathogen populations to shifting arrays of host species. While our knowledge of emerging diseases is, for the most part, limited to the time span of the human lineage, this history provides us with a modern reflection of these deeper evolutionary processes, and it is clear from this record that at many times throughout human history, demographic and behavioural changes in society have provided opportunities for pathogens to emerge. PMID- 17848063 TI - Infection and disease in reservoir and spillover hosts: determinants of pathogen emergence. AB - Infection and disease in reservoir and spillover hosts determine patterns of infectious agent availability and opportunities for infection, which then govern the process of transmission between susceptible species. In this chapter, using the zoonotic agents Hendra virus and Nipah virus as examples, the pathogenesis of infection in various species including the wildlife reservoirs and domestic spillover hosts is reviewed with an emphasis on the aspects of pathogenesis which contribute to the dissemination of infection. Through these discussions, the emergence of these zoonotic agents is explored. PMID- 17848064 TI - Henipaviruses: emerging paramyxoviruses associated with fruit bats. AB - Two related, novel, zoonotic paramyxoviruses have been described recently. Hendra virus was first reported in horses and thence humans in Australia in 1994; Nipah virus was first reported in pigs and thence humans in Malaysia in 1998. Human cases of Nipah virus infection, apparently unassociated with infection in livestock, have been reported in Bangladesh since 2001. Species of fruit bats (genus Pteropus) have been identified as natural hosts of both agents. Anthropogenic changes (habitat loss, hunting) that have impacted the population dynamics of Pteropus species across much of their range are hypothesised to have facilitated emergence. Current strategies for the management of henipaviruses are directed at minimising contact with the natural hosts, monitoring identified intermediate hosts, improving biosecurity on farms, and better disease recognition and diagnosis. Investigation of the emergence and ecology of henipaviruses warrants a broad, cross-disciplinary ecosystem health approach that recognises the critical linkages between human activity, ecological change, and livestock and human health. PMID- 17848065 TI - Emergence of lyssaviruses in the Old World: the case of Africa. AB - Rabies has a long history of occurrence throughout Africa, spanning hundreds of years. At least four distinct Lyssavirus species persist throughout the continent, among carnivores, bats and other mammals. Rabies virus is the most cosmopolitan member, with primary reservoirs within dogs and mongoose, but other wildlife vectors are important in viral maintenance, such as jackals. Besides a prominent toll on humans and domestic animals, the disease has an underappreciated role in conservation biology, especially for such highly endangered fauna as African wild dogs and Ethiopian wolves. Both Duvenhage and Lagos bat viruses are adapted to bats, but their epidemiology, together with Mokola virus, is poorly understood. Significantly, less than ideal cross reactivity with modern biologicals used for veterinary and public health interventions is a major cause for concern among these emerging viral agents. PMID- 17848066 TI - Tuberculosis: a reemerging disease at the interface of domestic animals and wildlife. AB - Complex interactions involving humans, domestic animals, and wildlife create environments favorable to the emergence of new diseases. Today, reservoirs of Mycobacterium bovis, the causative agent of tuberculosis in animals and a serious zoonosis, exist in wildlife. The presence of these wildlife reservoirs is the direct result of spillover from domestic livestock in combination with anthropogenic factors such as translocation of wildlife, supplemental feeding of wildlife and wildlife populations reaching densities beyond normal habitat carrying capacities. As many countries attempt to eradicate M. bovis from domestic livestock, efforts are impeded by spillback from wildlife reservoirs. It will not be possible to eradicate M. bovis from livestock until transmission between wildlife and domestic animals is halted. Such an endeavor will require a collaborative effort between agricultural, wildlife, environmental and political interests. PMID- 17848067 TI - Emergence and persistence of hantaviruses. AB - Hantaviral diseases have been recognized for hundreds of years but, until 1976, they had not been associated with an infectious agent. When Lee and colleagues isolated what is now known as Hantaan virus, the techniques they introduced allowed further investigations into the etiology of the classical hantavirus disease, hemorrhagic fever with renal syndrome (HFRS), now known to be caused by any of multiple hantaviruses. The discovery of hantavirus pulmonary syndrome (HPS) in the New World, and that it also can be caused by any of multiple hantaviruses (family Bunyaviridae, genus Hantavirus), has opened an entire field of epidemiologic, virologic, molecular, behavioral, and ecologic studies of these viruses. There appears to be a single hantavirus-single rodent host association, such that understanding the idiosyncrasies of each rodent host species and the ecologic variables that affect them are recognized as critical if we are to reduce human risk for infection. This chapter summarizes what is known about hantaviruses with regard to history of these viruses, their taxonomy, recognized geographical distribution, ecologic factors impacting their maintenance and spread of hantaviruses, effect of rodent behavior on hantavirus transmission, influence of host factors on susceptibility to and transmission of hantaviruses, and transmission of hantaviruses from rodents to humans. In addition, we summarize all these complexities and provide suggestions for future research directions. PMID- 17848068 TI - Arenaviruses. AB - The Arenaviridae family contains 22 recognized virus species, each of them strongly associated with a rodent species (except Tacaribe virus which is associated with a species of bat), suggesting an ancient co-evolutionary process. Although the concept of co-evolution between rodents and arenaviruses is now largely accepted, little has been uncovered in terms of dating the phenomenon and the mechanisms of evolution, including speciation and pathogenicity. These questions are targeted in the present chapter. Old World arenaviruses are associated with the Eurasian rodents in the family Muridae. New World arenaviruses are associated with American rodents in the subfamily Sigmodontinae. The correlation between the rodent host phylogeny and the viruses suggests a long association and a co-evolutionary process. Furthermore, three distinct New World arenaviruses share a common ancestor, demonstrating a unique recombination event that probably occurred in that ancestor. This shows that recombination among arenaviruses of different lineages might occur in nature. Recombination and co evolutionary adaptation appear as the main mechanisms of arenavirus evolution, generating a high degree of diversity. The diversity among rodent host reservoir and virus species and the potential to exchange genomic material provide a basis for the emergence of new viruses and the risk of these becoming pathogenic for humans. PMID- 17848069 TI - Ecological havoc, the rise of white-tailed deer, and the emergence of Amblyomma americanum-associated zoonoses in the United States. AB - Two infectious diseases, and one presumably infectious disease, each vectored by or associated with the bite of the lone star tick (Amblyomma americanum), were identified and characterized by clinicians and scientists in the United States during the 1980s and 1990s. These three conditions-human monocytic (or monocytotropic) ehrlichiosis (HME), Ehrlichia ewingii ehrlichiosis, and southern tick-associated rash illness (STARI)-undoubtedly existed in the United States prior to this time. However, the near-simultaneous recognition of these diseases is remarkable and suggests the involvement of a unifying process that thrust multiple pathogens into the sphere of human recognition. Previous works by other investigators have emphasized the pivotal role of white-tailed deer (Odocoileus virginianus) in the emergence of Lyme disease, human babesiosis, and human granulocytic anaplasmosis. Because whitetails serve as a keystone host for all stages of lone star ticks, and an important reservoir host for Ehrlichia chaffeensis, E. ewingii, and Borrelia lonestari, the near-exponential growth of white-tailed deer populations that occurred in the eastern United States during the twentieth century is likely to have dramatically affected the frequency and distribution of A. americanum-associated zoonoses. This chapter describes the natural histories of the pathogens definitively or putatively associated with HME, E. ewingii ehrlichiosis, and STARI; the role of white-tailed deer as hosts to lone star ticks and the agents of these diseases; and the cascade of ecologic disturbances to the landscape of the United States that have occurred during the last 200 years that provided critical leverage in the proliferation of white tailed deer, and ultimately resulted in the emergence of these diseases in human populations. PMID- 17848070 TI - Bats, civets and the emergence of SARS. AB - Severe acute respiratory syndrome (SARS) was the first pandemic transmissible disease of previously unknown aetiology in the twenty-first century. Early epidemiologic investigations suggested an animal origin for SARS-CoV. Virological and serological studies indicated that masked palm civets ( Paguma larvata), together with two other wildlife animals, sampled from a live animal market were infected with SARS-CoV or a closely related virus. Recently, horseshoe bats in the genus Rhinolophus have been identified as natural reservoir of SARS-like coronaviruses. Here, we review studies by different groups demonstrating that SARS-CoV succeeded in spillover from a wildlife reservoir (probably bats) to human population via an intermediate host(s) and that rapid virus evolution played a key role in the adaptation of SARS-CoVs in at least two nonreservoir species within a short period. PMID- 17848071 TI - Poxviruses and the passive quest for novel hosts. AB - Poxviruses are famous, or infamous, as agents of disease introduced into novel host species and between populations of the same species. This discussion concerns selected examples of poxviruses associated with vertebrate infections, i.e., the Chordopoxvirus subfamily of the family Poxviridae. Brief note is made of examples of members of the genera Leporipoxvirus and Parapoxvirus-like agents that have been recognized to have significant trans-host species impact. The remaining bulk of the discussion involves examples of members of the genus Orthopoxvirus, which are known to be (have been) involved with human disease, and their zoonotic origins. PMID- 17848072 TI - Ebolavirus and other filoviruses. AB - Since Ebola fever emerged in Central Africa in 1976, a number of studies have been undertaken to investigate its natural history and to characterize its transmission from a hypothetical reservoir host(s) to humans. This research has comprised investigations on a variety of animals and their characterization as intermediate, incidental, amplifying, reservoir, or vector hosts. A viral transmission chain was recently unveiled after a long absence of epidemic Ebola fever. Animal trapping missions were carried out in the Central African rain forest in an area where several epidemics and epizootics had occurred between 2001 and 2005. Among the various animals captured and analyzed, three species of fruit bats (suborder Megachiroptera) were found asymptomatically and naturally infected with Ebola virus: Hypsignathus monstrosus (hammer-headed fruit beats), Epomops franqueti (singing fruit bats), and Myonycteris torquata (little collared fruit bats). From experimental data, serological studies and virus genetic analysis, these findings confirm the importance of these bat species as potential reservoir species of Ebola virus in Central Africa. While feeding bats drop partially eaten fruit and masticated fruit pulp (spats) to the ground, possibly promoting indirect transmission of Ebola virus to certain ground dwelling mammals, if virus is being shed in saliva by chronically and asymptomatically infected bats. Great apes and forest duikers are particularly sensitive to lethal Ebola virus infection. These terrestrial mammals feed on fallen fruits and possibly spats, suggesting a chain of events leading to Ebola virus spillover to these incidental hosts. This chain of events may occur sporadically at different sites and times depending on a combination of the phenology of fruit production by different trees, animal behavior, and various, but as yet still unknown environmental factors, which could include drought. During the reproductive period, infected body fluid can also be shed in the environment and present a potential risk for indirect transmission to other vertebrates. PMID- 17848073 TI - Pre-spillover prevention of emerging zoonotic diseases: what are the targets and what are the tools? AB - The uneven standards of surveillance, human- or animal-based, for zoonotic diseases or pathogens maintained and transmitted by wildlife H(R)s, or even domestic species, is a global problem, readily apparent even within the United States, where investment in public health, including surveillance systems, has a long and enviable history. As of 2006, there appears to be little scientific, social, or political consensus that animal-based surveillance for zoonoses merits investment in international infrastructure, other than the fledgling efforts with avian influenza, or targeted nontraditional avenues of surveillance and research. National institutions charged with strategic planning for emerging diseases or intentional releases of zoonotic agents have emphasized improving diagnostic capabilities for detecting human infections, modifying the immune status of human or domestic animals through vaccines, producing better antiviral or antibacterial drugs, and enhancing human-based surveillance as an early warning system. With the possible exception of extensive human vaccination, each of these approaches target post-spillover events and none of these avenues of research will have the slightest impact on reducing the risk of additional emergence of viruses or other pathogens from wildlife. Novel schemes of preventing spillover of human pathogens from animal H(R)s can only spring from improving our understanding of the ecological context and biological interactions of pathogen maintenance among H(R)s. Although the benefit derived from investments to improve surveillance and knowledge of zoonotic pathogens circulating among wildlife H(R) populations is uncertain, our experience with HIV and the looming threat of pandemic avian influenza A inform us of the outcomes we can expect by relying on detection of post-spillover events among sentinel humans. PMID- 17848074 TI - Impediments to wildlife disease surveillance, research, and diagnostics. AB - There is a recognized need for increased wildlife disease surveillance and research related to understanding the epidemiology and control of emerging wildlife and zoonotic diseases. Although both passive and active surveillance strategies can and have been effectively used with wildlife, some unique problems are often encountered. These can include limitations related to case acquisition and under-reporting, difficulty in designing sampling strategies that adequately represent the population of interest, the lack of properly validated diagnostic tests, problems related to data interpretation due to missing or inaccurate denominator data, and the lack of an existing wildlife surveillance infrastructure. Many of these same problems are often encountered in field research, which can be further complicated by the complexity and scale of the natural systems in which this work takes place. Although such studies may be difficult, there are numerous examples of success and our understanding of wildlife and wildlife-related zoonotic and emerging disease continues to grow. PMID- 17848075 TI - Collaborative research approaches to the role of wildlife in zoonotic disease emergence. AB - Emerging infectious diseases are a key threat to public health and the majority are caused by zoonotic pathogens. Here we discuss new collaborative approaches to understanding the process of zoonotic disease emergence that link veterinary medicine, public health, and ecological approaches: conservation medicine and one health. We demonstrate how studies on the underlying drivers of disease emergence (bushmeat hunting, wildlife trade, and deforestation) can provide ways to model, predict, and ultimately prevent zoonotic disease emergence and spread. PMID- 17848076 TI - Surveillance and response to disease emergence. AB - New and emerging infectious diseases affect humans, domestic animals, livestock and wildlife and can have a significant impact on health, trade and biodiversity. Of the emerging infectious diseases of humans, 75% are zoonotic, with wildlife being an increasingly important source of inter-species transmission. Recent animal health emergencies have highlighted the vulnerability of the livestock sector to the impact of infectious diseases and the associated risks to human health. Outbreaks resulting from wildlife trade have resulted in enormous economic losses globally. On a global level, the human health sector lags behind the animal health sector in the assessment of potential threats, although substantive differences exist among countries in the state of national preparedness planning for emerging diseases. The lack of surveillance data on emerging zoonoses from many developing countries means that the burden of human, livestock and wildlife disease is underestimated and opportunities for control interventions thereby limited. In the context of emerging zoonoses, comprehensive risk assessments are needed to identify the animal-human and animal-animal interfaces where transmission of infectious agents occurs and the feasibility of risk reduction interventions. The impact of emerging diseases can be minimised through a well-prepared and strong public health system and similar systems developed by the livestock, wildlife and food safety sectors. National animal disease emergencies, especially those that spill over to affect human health, require a whole-of-government approach for effective disease containment. As it is highly likely that zoonoses and animal diseases with the potential to affect human health will continue to emerge, surveillance and response systems for emerging zoonotic diseases will need to be strengthened and maintained at national and international levels. Applied research, linked across the human, livestock and wildlife sectors, is needed to inform preparedness planning and the development of evidence-based approaches to zoonotic disease prevention and control. PMID- 17848077 TI - Conjugation of polyamidoamine dendrimers on biodegradable microparticles for nonviral gene delivery. AB - We report on the preparation and characterization of poly(D, L-lactide-co glycolide) (PLGA) microparticles with surface-conjugated polyamidoamine (PAMAM) dendrimers of varying generations. The buffering capacity and zeta-potential of the PLGA PAMAM microparticles increased with increasing generation level of the PAMAM dendrimer conjugated. Conjugation of the PAMAM dendrimer to the surface of the PLGA microparticle removed generation-dependent cytotoxicity in HEK293 and COS7 cell lines. PLGA PAMAM pDNA microparticles displayed similar cytotoxicity profiles to unmodified PLGA pDNA microparticles in COS7 cells. A generation three PAMAM dendrimer conjugated to PLGA microparticles significantly increased transfection efficiencies in comparison to unmodified PLGA microparticles. PMID- 17848078 TI - Synthesis and biosensor performance of a near-IR thiol-reactive fluorophore based on benzothiazolium squaraine. AB - Environmentally sensitive near-IR (NIR) dyes are useful fluorophores for various biosensor applications when tissue absorption, scattering, and autofluorescence are a leading concern. Biosensors operating in the NIR region (generally wavelengths >650 nm) would avoid interference from biological media and thereby facilitate relatively interference free sensing. Squaraine dyes are potential candidates to serve as reporter molecules due to their spectral properties in the NIR region, but none is commercially available for site-specific coupling to proteins through native or engineered thiols on cysteine. In this context, we have synthesized a thiol-reactive squaraine that displays fluorescence emission above 650 nm and have coupled the dye site-specifically to various mutants of glucose/galactose binding protein that contained an engineered cysteine for attachment. Mutant E149C/A213R/L238S ISQ GGBP gave a fluorescence change of +50% and a binding constant of 12 mM, which is in the human physiological range for glucose. PMID- 17848079 TI - Identification of flavonoids and hydroxycinnamic acids in pak choi varieties (Brassica campestris L. ssp. chinensis var. communis) by HPLC-ESI-MSn and NMR and their quantification by HPLC-DAD. AB - Twenty-eight polyphenols (11 flavonoid derivatives and 17 hydroxycinnamic acid derivatives) were detected in different cultivars of the Chinese cabbage pak choi ( Brassica campestris L. ssp. chinensis var. communis) by HPLC-DAD-ESI-MS(n). Kaempferol was found to be the major flavonoid in pak choi, glycosylated and acylated with different compounds. Smaller amounts of isorhamnetin were also detected. A structural determination was carried out by (1)H and (13)C NMR spectroscopy for the main compound, kaempferol-3-O-hydroxyferuloylsophoroside-7-O glucoside, for the first time. Hydroxycinnamic acid derivatives were identified as different esters of quinic acid, glycosides, and malic acid. The latter ones are described for the first time in cabbages. The content of polyphenols was determined in 11 cultivars of pak choi, with higher concentrations present in the leaf blade than in the leaf stem. Hydroxycinnamic acid esters, particularly malic acid derivatives, are present in both the leaf blade and leaf stem, whereas flavonoid levels were determined only in the leaf blade. PMID- 17848080 TI - pH-Dependent radical scavenging activity of folates. AB - Folic acid (FA) is used, in many countries, in nutritional supplements or for the fortification of cereals and their products. It is also used in vitamin pills. Recently, it was reported that folates may act as antioxidants; therefore, in the present study, the effect of pH of the surrounding medium on the radical scavenging activity of FA and its reduced forms [dihydrofolic acid (DHF), tetrahydrofolic acid (THF), 5-methyltetrahydrofolic acid (5-MTHF), and 5 formyltetrahydrofolic acid (5-FTHF)] was investigated. It was found that radical scavenging activities of folates, measured in the trolox equivalent antioxidant capacity (TEAC) assay, are strongly pH-dependent. FA is a better radical scavenger at acid and basic pH than at neutral pH. Reduced forms of FA are better radical scavengers at acidic pH values than at neutral and basic pH values, with exception of 5-FTHF for which, at a pH higher than 5.0, an increase of the radical-scavenging activity with an increasing pH of the medium is observed. The results of the present study indicate that possible health effects of folates associated with their radical-scavenging activity will vary depending upon the pH of body fluid or tissue considered. PMID- 17848081 TI - Dual laccase-tyrosinase based Sonogel-Carbon biosensor for monitoring polyphenols in beers. AB - A biosensor based on the bi-immobilization of laccase and tyrosinase phenoloxidase enzymes has been successfully developed. This biosensor employs as the electrochemical transducer the Sonogel-Carbon, a novel type of electrode developed by our group. The immobilization step was accomplished by doping the electrode surface with a mixture of the enzymes, glutaricdialdehyde, and Nafion ion exchanger, as protective additive. The response of this biosensor, denoted the dual Trametes versicolor laccase (La) and Mushroom tyrosinase (Ty) based Sonogel-Carbon, was optimized directly in beer real samples and its analytical performance with respect to five individual polyphenols was evaluated. The Lac Ty/Sonogel-Carbon electrode responds to nanomolar concentrations of flavan-3-ols, hydroxycinnamic acids, and hydroxybenzoic acids. The limit of detection, sensitivity, and linear range for caffeic acid, taken as an example, were 26 nM, 167.53 nA M (-1), and 0.01-2 microM, respectively. In addition, the stability and reproducibility of the biosensor were also evaluated in beer samples. The Lac Ty/sonogel-carbon electrode was verified as very stable in this matrix, maintaining 80% of its stable response for at least three weeks, with a RSD of 3.6% ( n = 10). The biosensor was applied to estimate the total polyphenol index in ten beer samples, and a correlation of 0.99 was obtained when the results were compared with those obtained using the Folin-Ciocalteau reagent. PMID- 17848082 TI - Environmentally induced changes in amino acid composition in the grain of durum wheat grown under different water and temperature regimes in a Mediterranean environment. AB - Amino acid composition is an important feature in determining the nutritional value of wheat grain for human and animal diets. Environmental conditions are known to influence protein quantity as well as grain production and, in turn, amino acid composition. In this study, grain yield, protein content, and amino acid composition were determined in 10 durum wheat genotypes under three water and temperature regimes in a Mediterranean environment. The highest value for grain-protein content (15.7%) was found in the warmer and driest environment and the lowest (12.8%) in the irrigated environment. Although amino acid composition showed significant variation for all genotypes, with the exception of arginine and cysteine, major changes in amino acid composition were caused by environmental conditions and in particular by water availability and temperature during the grain-filling period, which significantly altered the duration of grain development. The amino acids with the highest percentage of variation between environments were tyrosine (26.4%), lysine (23.7%), methionine (20.3%), threonine (19.3%), and valine (15.6%), whereas phenylalanine (5.1%), glycine (6.4%), and aspartic acid (6.8%) showed the least variation between environments. Whereas the content of glutamine, phenylalanine, and proline increased with the decrease in grain-filling duration, the remaining amino acids tended to diminish, presumably because high temperature and drought favored the deposition of gliadins (proteins particularly rich in glutamine and proline), to the detriment of albumins and globulins (proteins especially rich in threonine, lysine, methionine, valine, and histidine). Despite the negative correlations found between the percentage of protein and its content in essential amino acids, the results indicate that reductions in lysine per unit of food were not very pronounced (0.32 to 0.29 g/100 g of flour) with increases of up 22.7% in grain protein content, whereas threonine did not change and valine even slightly increased. PMID- 17848083 TI - Effect of 60Co-irradiation on postharvest quality and selected enzyme activities of Hypsizygus marmoreus fruit bodies. AB - Hypsizygus marmoreus fruit bodies were exposed to different doses of (60)Co gamma irradiation, stored at 4 degrees C and 65-70% relative humidity, and various physiological changes associated with postharvest deterioration, as well as the activities of selected enzymes widely considered to play a role in the process of senescence, were monitored over a subsequent storage period of 25 days. Exposure to 0.8 kGy irradiation was clearly beneficial in maintaining the postharvest appearance of the mushroom sporophores compared to non-irradiated samples and fruit bodies exposed to higher doses (1.2-2.0 kGy) of irradiation. Samples treated with 0.8 kGy also exhibited smaller initial declines in soluble protein, smaller increases in reducing sugar content, and lower levels of malondialdehyde accumulation during the early storage period. Smallest increases in proteinase activity were recorded in samples dosed with 0.8 and 2.0 kGy, and levels of superoxide dismutase were significantly higher in samples exposed to 0.8 kGy compared with non-irradiated controls. Large initial increases in catalase activity were detected in samples irradiated with 0.8, 1.2, and 1.6 kGy and, although enzyme levels gradually decreased in all samples during further storage, residual levels after 25 days were still severalfold higher in irradiated samples compared with controls. The data increase the current understanding of the effects of gamma-irradiation on the biochemical changes associated with postharvest senescence and should lead to more targeted strategies for reducing postharvest quality loss in H. marmoreus and other mushrooms. PMID- 17848084 TI - Lipoxygenase distribution in coffee (Coffea arabica L.) berries. AB - In this paper lipoxygenase (LOX) presence was investigated in coffee berries to determine its involvement in lipid degradative metabolism of plants grown in organic and conventional cultivations. An immunochemical analysis has evidenced a ca. 80 kDa protein, cross-reacting with an anti-LOX antibody, only in the pulp fraction of berries obtained from plants of both cultivations. LOX activity in this fraction could be monitored either as conjugated diene formation or reaction products (determined by HPLC) and was mainly associated with a heavy membrane fraction (HMF, enriched in tonoplast, endoplasmic reticulum, plasma membrane, and mitochondria) and a light membrane fraction (LMF, enriched in plasma membrane and endoplasmic reticulum, with low levels of tonoplast and mitochondria). The LOX activity of LMF from berries of both cultivations showed an optimum at pH 8.0. The HMF exhibited a different activity peak in samples from conventional (pH 8.0) and organic (pH 5.5) cultures, suggesting the presence of different isoenzymes. These findings were also confirmed by variation of the ratio of 9- and 13 hydroperoxides in organic (1:1) and conventional cultivations (1:10), indicating that the organic one was subjected to an oxidative stress in the coffee pulp fraction leading to the expression of an acidic LOX. Such de novo synthesized LOX activity could be responsible for the production of secondary metabolites, which may interfere with the organoleptic profile of coffee. PMID- 17848085 TI - Effect of drip application of ammonium thiosulfate on fumigant degradation in soil columns. AB - Low permeability tarps can effectively minimize fumigant emissions while improving fumigation efficacy by retaining fumigants under the tarp. However, when planting holes are cut through the tarps, high-concentration fumigants may be released and result in environmental and worker safety hazards. In a 11-day column study, we explored the effect of drip irrigation application of ammonium thiosulfate (ATS) on 1,3-dichloropropene (1,3-D) and chloropicrin (CP) degradation in soil. Decrease of 1,3-D and CP concentrations in soil-gas phase followed a three-parameter logistic equation for all treatments. It was slowest in the control with a half-life ( t 1/2) of 86.0 h for 1,3-D and of 16.3 h for CP and most rapid when ATS was applied at 4:1 ATS/fumigant molar ratio with a half life of 9.5 h for 1,3-D and of 5.5 h for CP. Our results indicate that applying ATS via the drip-irrigation systems to soil can accelerate fumigant degradation in soil and thus reduce emissions. This technical solution may be applicable in raised-bed strawberry production where drip-application of fumigants under tarps has become common. PMID- 17848086 TI - Concentration of isoflavones and other phenolics in the aerial parts of Trifolium species. AB - Some species of the genus Trifolium are well-known for their content of isoflavones, which are natural compounds showing health-promoting activities. Until recently, only a few species of this genus have been characterized with respect to their composition. In the present study, 57 Trifolium species have been analyzed for their contents of isoflavones, phenolic acids, flavonoids, and clovamides. The cluster analysis of experimental data allowed us to identify a number of species, which should be of interest as potential sources of these metabolites. The isoflavone contents of the three species ( T. heldreichianum, T. scabrum, and T. subterraneum) had extremely high amounts of these compounds, reaching 7-9% of dry matter, and the concentration in a number of other species was higher or at least comparable to the amounts occurring in T. pratense, one of the major isoflavone sources for the nutraceutical industry. Several species contained high amounts of all four analyzed groups of phenolics (isoflavones, phenolic acids, flavonoids, and clovamides). These species may also be of great interest as the association of several groups of active molecules is highly desired for effective disease prevention. PMID- 17848087 TI - Depletion of folate-receptor-positive macrophages leads to alleviation of symptoms and prolonged survival in two murine models of systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease involving deposition of immune complexes in normal tissues and the consequent accumulation of immune cells and tissue injury. Activated macrophages are thought to contribute to disease pathogenesis by releasing inflammatory mediators that both cause direct tissue damage and attract other immune cells that augment inflammation. Previous studies in animal models of rheumatoid arthritis have shown that activated macrophages express a folate receptor that can be targeted with folate-linked haptens, leading to (1) marking of the activated macrophages with highly immunogenic haptens, (2) recognition of the marked cells by Fc receptor expressing immune cells, and (3) destruction of the antibody-coated macrophages by the body's own immune system. Here we demonstrate that the same folate-hapten targeted immunotherapy can greatly suppress symptoms of SLE in two animal models of the disease, resulting in reduced immune complex deposition, diminished damage to normal tissues, and prolonged animal survival. PMID- 17848088 TI - Cassane furanoditerpenoids from the seed kernels of Caesalpinia bonduc from Thailand. AB - Three new cassane furanoditerpenoids ( 1- 3), together with 13 known cassane diterpenes ( 4- 16), were isolated from the EtOAc extract of the seed kernels of Caesalpinia bonduc. Their structures were elucidated on the basis of spectroscopic analysis, mainly NMR and MS. Compounds 1- 3 exhibited good antimalarial activity against the multidrug-resistant K1 strain of Plasmodium falciparum, while compound 4 was inactive. None of the compounds were cytotoxic against any of the tumor cell lines tested. PMID- 17848089 TI - Renierosides, cerebrosides from a marine sponge Haliclona (Reniera) sp. AB - Guided by the brine shrimp lethality assay, eight new cerebrosides (1-8) have been isolated from an extract of the marine sponge Haliclona (Reniera) sp. A novel feature of these cerebrosides was the presence of unprecedented amide linked long-chain fatty acid moieties. The planar structures of the cerebrosides (1-8) were established by 1D and 2D NMR spectroscopic techniques, mass spectrometric analyses, and chemical degradation methods. The isolated compounds did not display cytotoxicity to a panel of five human solid tumor cell lines. PMID- 17848093 TI - Free radical functionalization of organic compounds catalyzed by N hydroxyphthalimide. PMID- 17848094 TI - Renaturation and purification of rhGM-CSF with ion-exchange chromatography. AB - The renaturation and purification of recombinant human granulocyte macrophage colony stimulation factor (rhGM-CSF) expressed in Escherichia coli with strong anion-exchange chromatography (SAX) were studied. The effects of pH values, ratios of concentrations of GSH/GSSG, and urea concentrations in the mobile phase on the renaturation and purification of rhGM-CSF with SAX were investigated, respectively. The results show that the above three factors have remarkable influences on the efficiency of renaturation and mass recovery of rhGM-CSF. The addition of GSH/GSSG in the mobile phase can improve the formation of correct disulfide bonds in rhGM-CSF so that its renaturation yield increases. In addition, to enhance the mass recovery of rhGM-CSF with SAX, the low concentration of urea was added in the mobile phase to prevent denatured protein aggregation. Under the optimal conditions, rhGM-CSF was renatured with simultaneous purification on SAX column within 30 min only by one step. After that its specific bioactivity, mass recovery, and purity reached 1.66 x 10(7) IU x mg, 58.8%, and 96.2%, respectively. PMID- 17848095 TI - Performance characteristics of nanoporous carbon membranes for protein ultrafiltration. AB - Nanoporous carbon membranes could be very attractive for applications of ultrafiltration in the biotechnology industry because of their greater mechanical strength and longer membrane life. The objective of this study was to obtain quantitative data on the performance characteristics of nanoporous carbon membranes formed within a stainless steel support that was first modified by deposition of silica particles within the macroporous support. The nanoporous carbon membrane effectively removed small solutes from a protein solution using diafiltration, with performance comparable to that of commercial polymeric membranes. Protein fouling was evident, although the nanoporous carbon membranes were easily regenerated; cleaning with 0.5 N NaOH at 50 degrees C completely restored the water permeability for multiple cycles. The nanoporous carbon membranes were also compatible with steam sterilization. Significant increases in process flux could be obtained using periodic back-pulsing, with no evidence of any structural alterations in the membrane. These results clearly demonstrate the potential benefits and opportunities for using nanoporous carbon membranes for protein ultrafiltration. PMID- 17848096 TI - Quantitative measurement of endogenous estrogens and estrogen metabolites in human serum by liquid chromatography-tandem mass spectrometry. AB - Endogenous estrogen plays a key role in the development of human breast cancer, yet the contribution of specific estrogen metabolites and patterns of estrogen metabolism remains unclear. To determine their individual and joint roles in breast carcinogenesis, it is necessary to be able to measure quantitatively each estrogen metabolite in epidemiologic and clinical biospecimens. In this report, we detail a sensitive, specific, accurate, and precise high-performance liquid chromatography-tandem mass spectrometry method utilizing selected reaction monitoring for measuring the absolute quantities of free (unconjugated) and total (conjugated + unconjugated) endogenous estrogens and estrogen metabolites in human serum from premenopausal and postmenopausal women. The method requires a simple sample preparation and only 0.5 mL of serum, yet is capable of quantifying simultaneously 15 estrogens and estrogen metabolites (EM): estrone and its 2-, 4 , and 16alpha-hydroxy and 2- and 4-methoxy derivatives; 2-hydroxyestrone-3-methyl ether; 17beta-estradiol and its 2-hydroxy and 2- and 4-methoxy derivatives; and estriol, 17-epiestriol, 16-ketoestradiol, and 16-epiestriol. The lower limit of quantitation for each EM was 0.4 pg on-column, equivalent to 8 pg/mL (26.5-29.6 fmol/mL) in the original serum sample. Calibration curves were linear over a 10(3)-fold concentration range. For a stripped serum sample containing 8 pg/mL of each EM, accuracy (percent recovery of a known added amount) ranged from 91 to 113%. Intrabatch precision (including hydrolysis, extraction, and derivatization steps) ranged from 7 to 30% relative standard deviation (RSD), and interbatch precision ranged from 8 to 29% RSD. Since distinct roles have been proposed for many of these estrogen metabolites, an accurate, precise, sensitive, and specific method for measuring their levels in circulation should suggest new approaches to breast cancer prevention, screening, and treatment. PMID- 17848097 TI - Streaming potential effects on solute dispersion in nanochannels. AB - This correspondence presents a theoretical analysis of the effects of streaming potential on the hydrodynamic dispersion of solutes in pressure-driven flow. The induced electroosmotic backflow is shown to significantly decrease the solute dispersion in slit nanochannels. The dispersion coefficient as traditionally defined may be significantly increased or decreased by streaming potential effects. These influences are sensitive to the solute charge, and found to be mainly dependent on an electrokinetic "figure of merit". PMID- 17848098 TI - Self-promoted cellular uptake of peptide/DNA transfection complexes. AB - The designed alpha-helical amphipathic peptide LAH4 assembles several properties, which makes it an interesting candidate as a gene-delivery vehicle. Besides being short and soluble in aqueous solutions, LAH4 presents cationic residues, which allow for efficient complexation of DNA. In addition, this peptide is poorly hemolytic at neutral pH, while it is able to destabilize biological membranes in acidic conditions. In this study, the structure of the peptide/DNA transfection complex was examined by circular dichroism and solid-state nuclear magnetic resonance spectroscopies and the thermodynamics of its formation and disassembly was monitored in a quantitative manner as a function of pH by isothermal titration calorimetry. Notably, the number of peptides within the complex considerably decreases upon acidification of the medium. This observation has direct and important consequences for the mechanism of action because the acidification of the endosome results in high local concentrations of free peptide in this organelle. Thus, these peptides become available to interact with the endosomal membranes and thereby responsible for the delivery of the transfection complex to the cytoplasm. When these data are taken together, they indicate a dual role of the peptide during the transfection process, namely, DNA complexation and membrane permeabilization. PMID- 17848099 TI - Overcoming resistance to beta-lactamase inhibitors: comparing sulbactam to novel inhibitors against clavulanate resistant SHV enzymes with substitutions at Ambler position 244. AB - Amino acid changes at Ambler position R244 in class A TEM and SHV beta-lactamases confer resistance to ampicillin/clavulanate, a beta-lactam/beta-lactamase inhibitor combination used to treat serious infections. To gain a deeper understanding of this resistance phenotype, we investigated the activities of sulbactam and two novel penem beta-lactamase inhibitors with sp2 hybridized C3 carboxylates and bicyclic R1 side chains against a library of SHV beta-lactamase variants at the 244 position. Compared to SHV-1 expressed in Escherichia coli, all 19 R244 variants exhibited increased susceptibility to ampicillin/sulbactam, an important difference compared to ampicillin/clavulanate. Kinetic analyses of SHV-1 and three SHV R244 (-S, -Q, and -L) variants revealed the Ki for sulbactam was significantly elevated for the R244 variants, but the partition ratios, kcat/kinact, were markedly reduced (13 000 --> 0.05), but analysis of a homogeneity-of-slopes model showed that genotype had a significant influence on HOMA-IR (p=0.037), and the interaction between genotype and HDL-C had a pronounced tendency to affect HOMA-IR (p=0.058). Using multiple regression analysis, we found that HDL-C had a significant effect on HOMA-IR (p=0.023), and TG had a tendency to affect HOMA-IR (p=0.066) only in the CC genotype. CONCLUSIONS: Our data show that IL-6 -174G/C polymorphism may have a significant effect on IR. A comparison between the effects of various cardiovascular risk factors showed that HDL-C may have a significant effect on HOMA-IR in the CC genotype but not in the GG genotype. Further research is needed to test the preliminary results. PMID- 17848120 TI - Apolipoprotein E polymorphism--a risk factor for metabolic syndrome. AB - BACKGROUND: Metabolic syndrome is closely related to several disturbances in lipid and lipoprotein metabolism. The aim of this study was to determine the association between apolipoprotein E (apoE) genotypes and the risk of metabolic syndrome and/or coronary heart disease complications. METHODS: The study included 279 subjects divided into three groups: 1) control subjects, 2) metabolic syndrome patients, and 3) obese patients with coronary heart disease. All subjects were characterized by body mass index, and plasma levels of glucose, triglycerides, cholesterol, high-density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). ApoE genotypes were identified by PCR restriction fragment length polymorphism using genomic DNA. RESULTS: Statistical analysis of plasma parameters showed that subjects in groups 2 and 3 had higher levels of triglycerides and lower levels of HDL-C compared to group 1. The frequencies of apoE genotypes determined in this Romanian population (65% for E3/3, 19.6% for E4/3, 9.5% for E3/2, 4.1% for E2/2, 0.6% for E4/4, 1.3% for E4/2) were in agreement with those reported for other Caucasian populations. The distribution of apoE alleles indicated a higher frequency of epsilon4 in groups 2 and 3. There was a higher frequency of the apoE4/3 genotype in groups 2 and 3, which was significantly correlated with higher levels of triglycerides and lower levels of HDL-C. CONCLUSIONS: Correlations of apoE genotypes with these markers indicate that the epsilon4 allele is an independent risk factor for metabolic syndrome. PMID- 17848121 TI - Association between the TaqIB polymorphism in the cholesteryl ester transfer protein gene locus and postprandial plasma lipoprotein levels in heterozygotes for familial hypercholesterolemia. AB - BACKGROUND: We examined the influence of cholesteryl ester transfer protein TaqIB polymorphism on triglyceride (TG) response to an oral fat tolerance test (OFTT) in patients heterozygous for familial hypercholesterolemia (hFH). METHODS: We genotyped 67 hFH patients (32 men and 35 postmenopausal women) who were subjected to an OFTT. RESULTS: All B1 allele carriers had lower high-density lipoprotein cholesterol (HDL-C) levels (p=0.013) and higher postprandial TG response at 6 and 8 h (p=0.05 and p=0.04, respectively) compared to B2 allele carriers. Multiple regression analysis showed that in the hFH group with a positive response, the presence of the B2 allele was significantly related to lower levels of TG-area under the curve (AUC) (p<0.01) compared to B1, adjusting for age, gender and body mass index. In the hFH group with a negative response, although age and female gender had a significant effect on TG-AUC levels (p<0.01 for both), the allele type was not significantly related to the TG-AUC levels (p=0.99). CONCLUSIONS: B2 carriers had a lower postprandial TG response compared to B1 carriers. There were no differences in TG levels between B1 and B2 carriers in patients with a negative OFTT response. Therefore, at higher TG concentration, the B2 allele may protect against an exaggerated postprandial TG increase and subsequent lowering of HDL-C. PMID- 17848122 TI - Intra-individual variation in creatinine and cystatin C. AB - BACKGROUND: Serum creatinine and cystatin C are measured in the assessment of glomerular filtration rate. Biological variation of an analyte is an important determinant of its usefulness. Intra-individual variation in serum creatinine and cystatin C in healthy subjects was determined in this study. METHODS: Weekly blood samples were taken from 10 healthy subjects and analysed for creatinine (kinetic Jaffe method) and for cystatin C (by nephelometry). RESULTS: Intra individual variations for serum creatinine and cystatin C were 6.1% and 4.55%, respectively. Index of individuality values were similar for the analytes (0.35 for both). CONCLUSION: Intra-individual variations for serum creatinine and cystatin C were similar in healthy subjects. PMID- 17848123 TI - Type B natriuretic peptide stability in frozen plasma. PMID- 17848124 TI - Differential impairment of patients with right versus left hemisphere lesions on the Ruff-light Trail Learning Test. AB - The Ruff-Light Trail Learning Test (RULIT) was developed as a neuropsychological measure of visuospatial learning and memory. RULIT scores of patients with right hemisphere and left hemisphere damage, as well as matched controls were compared. Right hemisphere lesion patients scored significantly lower on RULIT measures than did left hemisphere lesion patients and controls. The performance of left hemisphere lesion patients and controls did not differ significantly on RULIT measures. Adequate clinical hit rates, sensitivity and specificity in identifying right hemisphere damaged patients were demonstrated. PMID- 17848125 TI - Child-onset idiopathic seizures and specific learning disability: comorbidities in adults. AB - In this study, neuropsychological test data and demographic information were collected from 267 adults participating in evaluations as part of their involvement with a Vocational Rehabilitation service. Specifically targeted in this research was an assessment of the comorbidity and character of specific learning disabilities (LD) among individuals with a history of idiopathic seizures. Most participants were found to have reduced general cognitive performance. Persons with seizures performed more like LD adults than a control group of adults with non-seizure-related physical disabilities. This was true for many in the seizure group even when no prior LD had been diagnosed. Specific LDs were found in roughly one-third of adults with seizures. An analysis of diagnostic accuracy was conducted revealing higher than expected rates of Type I and Type II errors for persons who had previously carried an LD diagnosis. Strengths and limitations of the study were discussed along with a particular focus on implications for practicing neuropsychologists in educational and vocational settings, and for other professionals who might be responsible for the care of adults with a history of idiopathic seizure disorders. PMID- 17848126 TI - NEUROPSI ATTENTION AND MEMORY: a neuropsychological test battery in Spanish with norms by age and educational level. AB - Health care professionals are now faced with a growing number of patients from different ethnic groups, and from different socioeconomical backgrounds. In the field of neuropsychology there is an increasing need of reliable and culturally fair assessment measures. Spanish is the official language in more than 20 countries and the second most spoken language in the world. The purpose of this research was to develop and standardize the neuropsychological battery NEUROPSI ATTENTION AND MEMORY, designed to assess orientation, attention and concentration, executive functions, working memory and immediate and delayed verbal and visual memory. The developmental sequences of attention and memory as well as the educational effects were analyzed in a sample of 521 monolingual Spanish Speaking subjects, aged 6 to 85 years. Educational level ranged from 0 to 22 years of education. The consideration of the developmental sequence, and the effects of education, can improve the sensitivity and specificity of neuropsychological measures. PMID- 17848127 TI - Examining the relationship between WAIS-III premorbid intellectual functioning and WMS-III memory ability to evaluate memory impairment. AB - The purpose of this study was to extend previous research by Lange and Chelune (2006) by evaluating the clinical utility of GAI-memory discrepancy scores to detect memory impairment using estimated premorbid GAI scores (i.e., GAI-E) rather than obtained GAI scores. Participants were 34 patients with Alzheimer's type dementia and a sub-sample of 34 demographically matched participants from the WAIS-III/WMS-III standardization sample. GAI-memory discrepancy scores were more effective at differentiating Alzheimer's patients versus healthy controls when using estimated premorbid GAI scores than obtained GAI scores. However, GAI(E)-memory discrepancy scores failed to provide unique interpretive information beyond that which is gained from interpretation of the memory index scores alone. This was most likely due to the prevalence of obvious memory impairment in this patient population. Future research directions are discussed. PMID- 17848128 TI - Frequency of abnormal scores on the Neuropsychological Assessment Battery Screening Module (S-NAB) in a mixed neurological sample. AB - The Neuropsychological Assessment Battery (NAB; Stern & White, 2003; White & Stern, 2003) is a comprehensive, modular battery of tests comprised of the following six modules: (a) Screening, (b) Attention, (c) Language, (d) Memory, (e) Spatial, and (f) Executive Functions. The Screening Module is an abbreviated version of the full NAB. The purpose of this descriptive study was to present index and primary test score information for the Screening Module in a mixed sample of patients with known neurological conditions. Participants were 37 outpatients with clear evidence of neurological damage or disease. Performance decrements were found on the Attention Index, most notably on the Numbers and Letters tests. Decrements were also found on the Executive Functions Index, most notably on the Word Generation test. Somewhat surprisingly, patients performed well across most of the individual test scores. This mixed clinical sample showed less neuropsychological compromise than the clinical samples presented in the NAB manual. PMID- 17848129 TI - The influence of ethnicity on Symbol Digit Modalities Test performance: an analysis of a multi-ethnic college and hepatitis C patient sample. AB - Neuropsychologists routinely assess patients from racially, ethnically, and culturally diverse populations. Despite this fact, there remains a paucity of research investigating the influence of these variables on neuropsychological test performance. The Symbol Digit Modalities Test (SDMT) is a widely used measure of attention, visual scanning and tracking, and psychomotor speed. The purpose of the present study was to assess the relation between ethnicity and SDMT performance in ethnically diverse cognitively normal and cognitively impaired samples. Participants were 168 college students (81 Caucasian, 49 African American, 20 Asian American, and 18 Hispanic) and 24 patients (12 Caucasian and 12 Hispanic) chronically infected with hepatitis C. Results revealed no significant group differences in SDMT performance in either the student or patient sample. Furthermore ethnicity accounted for only 2 and 3 percent of the variance in SDMT scores for the patient and student samples, respectively. These findings provide preliminary support for the use of the SDMT across ethnically diverse populations in both clinical and normal samples though further analysis is warranted. PMID- 17848130 TI - Symptom exaggeration by college adults in attention-deficit hyperactivity disorder and learning disorder assessments. AB - To test the hypothesis that sub-optimal effort detected by one popular symptom validity measure, the Word Memory Test (WMT), should be interpreted as symptom exaggeration, the authors examined attention-deficit hyperactivity disorder (ADHD) and learning disorder (LD) assessment data collected from healthy adult patients over the past four years at one mid-size Southeastern college. They conducted six tests of this hypothesis, drawing upon extant research. Rates of apparent symptom exaggeration comparable to those found in medicolegal settings (e.g., personal injury cases), particularly in the context of ADHD evaluations, were found. WMT scores were positively correlated with intellectual and neurocognitive test scores, and negatively correlated with self-report symptom inventory scores. Measures of negative response bias embedded in one common self report measure of psychopathology (the Personality Assessment Inventory) were not correlated with WMT performance. Unattended WMT administrations led to somewhat higher failure rates than were found when the examiners were present in the room during all phases of the test's administration. In light of considerable secondary gain motives in this population, the authors conclude that poor effort as evidenced by low WMT scores implies symptom exaggeration and not other factors in these assessments. The routine inclusion of empirically supported symptom validity measures in these evaluations is recommended, and future research directions are suggested. PMID- 17848131 TI - Relationship between executive functioning and activities of daily living in patients with relatively mild dementia. AB - There is very little research regarding the relationship between tests of executive functioning and actual functional ability in patients with dementia. Thirty-three patients diagnosed with dementia and 35 age- and education-matched healthy controls were administered tests of executing functioning and an observation- and informant-based activities of daily living (ADL). As expected, the results revealed that the controls outperformed the dementia patients on the executive and ADL tests. Additionally, executive functioning correlated significantly with aspects of functional ability in patients with dementia. This relationship was strongest for tests of verbal fluency and a complex test of cognitive flexibility and reasoning ability (i.e., Wisconsin Card Sorting Test). These findings suggest that some executive function tests are more sensitive than others for predicting specific functional abilities and that they may be most useful to healthcare professionals for treatment planning. PMID- 17848132 TI - Geriatric performance on an abbreviated version of the Boston naming test. AB - Abbreviated neuropsychological protocols are increasingly utilized secondary to time-constraints within research and healthcare settings, yet normative data for these abbreviated instruments are lacking. We present geriatric performances and normative data for the Boston Naming Test 30-item even version (BNT-30). Data were utilized from the BU-ADCC registry (n = 441, ages 55-98) and included 219 normal controls (NC), 155 participants with mild cognitive impairment (MCI), and 67 participants with Alzheimer's disease (AD). The NC group (M = 28.7, SD = 1.8) significantly outperformed both MCI (M = 26.2, SD = 4.4) and AD (M = 22.1, SD = 4.8) groups, and the MCI group outperformed the AD group. Normative data generated for the NC participants revealed a significant between-group difference for sex (males M = 29.1, SD = 1.7; females M = 28.4, SD = 1.8) and race (White M = 28.8, SD = 1.7; African American M = 27.5, SD = 2.1). The racial disparity remained even after adjusting for education level (p = .002) and literacy (p < .001). ANOVAs for the NC group were non-significant for age but significant for education level (p = .001). Geriatric normative data therefore suggest that sex, race, and education are all associated with naming performance, and these variables should be taken into consideration when interpreting geriatric BNT-30 performance. PMID- 17848133 TI - Early detection of risk of onset for dementia of the Alzheimer type and subtle executive dysfunction after TBI using the test of verbal conceptualization and fluency during clinical neuropsychological assessment: two case studies. AB - Two case reports are presented that illustrate the use of a new assessment instrument of executive skills, the Test of Verbal Conceptualization and Fluency (TVCF), as a component of a clinical neuropsychological assessment. The cases presented include the assessment of a patient at risk of developing Alzheimer's disease and a patient with subtle signs of executive dysfunction subsequent to a mild head injury. Both patients had high levels of education and occupational status. The TVCF demonstrated clinical sensitivity to central nervous system (CNS) insult and results similar to those obtained with other established measures of executive functioning. PMID- 17848135 TI - TEST REVIEW: Alzheimer's Quick Test: Assessment Of Parietal Lobe Function. PMID- 17848136 TI - Apoptin: therapeutic potential of an early sensor of carcinogenic transformation. AB - The avian virus-derived protein apoptin induces p53-independent apoptosis in a tumor-specific way. Apoptin acts as a multimeric complex and forms superstructures upon binding to DNA. In tumor cells, apoptin is phosphorylated and mainly nuclear, whereas in normal cells it is unphosphorylated, cytoplasmic, and becomes readily neutralized. Interestingly, apoptin phosphorylation, nuclear translocation, and apoptosis can transiently be induced in normal cells by cotransfecting SV40 large T oncogene, indicating that apoptin recognizes early stages of oncogenic transformation. In cancer cells, apoptin appears to recognize survival signals, which it is able to redirect into cell death impulses. Apoptin targets include DEDAF, Nur77, Nmi, Hippi, and the potential drug target APC1. Apoptin-transgenic mice and animal tumor models have revealed apoptin as a safe and efficient antitumor agent, resulting in significant tumor regression. Future antitumor therapies could use apoptin either as a therapeutic bullet or as an early sensor of druggable tumor-specific processes. PMID- 17848138 TI - Genomic location of the human RNA polymerase II general machinery: evidence for a role of TFIIF and Rpb7 at both early and late stages of transcription. AB - The functions ascribed to the mammalian GTFs (general transcription factors) during the various stages of the RNAPII (RNA polymerase II) transcription reaction are based largely on in vitro studies. To gain insight as to the functions of the GTFs in living cells, we have analysed the genomic location of several human GTF and RNAPII subunits carrying a TAP (tandem-affinity purification) tag. ChIP (chromatin immunoprecipitation) experiments using anti tag beads (TAP-ChIP) allowed the systematic localization of the tagged factors. Enrichment of regions located close to the TIS (transcriptional initiation site) versus further downstream TRs (transcribed regions) of nine human genes, selected for the minimal divergence of their alternative TIS, were analysed by QPCR (quantitative PCR). We show that, in contrast with reports using the yeast system, human TFIIF (transcription factor IIF) associates both with regions proximal to the TIS and with further downstream TRs, indicating an in vivo function in elongation for this GTF. Unexpectedly, we found that the Rpb7 subunit of RNAPII, known to be required only for the initiation phase of transcription, remains associated with the polymerase during early elongation. Moreover, ChIP experiments conducted under stress conditions suggest that Rpb7 is involved in the stabilization of transcribing polymerase molecules, from initiation to late elongation stages. Together, our results provide for the first time a general picture of GTF function during the RNAPII transcription reaction in live mammalian cells and show that TFIIF and Rpb7 are involved in both early and late transcriptional stages. PMID- 17848140 TI - Long-term histological and immunohistochemical findings in human venous aorto coronary bypass grafts. AB - The aim of the present study was to analyse the long-term histology and immunohistochemistry of the plaque composition and cellular infiltration of SVGs (saphenous vein grafts) containing metallic stents. Percutaneous interventions in SVGs have a worse long-term clinical outcome compared with stenting of coronary arteries. Whether the pathological features of old degenerated SVGs condition the efficacy of drug-eluting stents is also unknown. Histology and immunohistochemistry of seven SVGs in the coronary circulation containing 12 metallic stents implanted 5 to 61 months before retrieval were analysed in patients undergoing a second aorto-coronary bypass surgery at a mean time of 11+/ 6 years. The pathology of the old SVGs showed an important thrombotic and necrotic composition of the plaque, with plaque protrusion through the stent wires and a fragile media layer that could easily be damaged by stent placement with subsequent neointimal proliferation; indeed, stents with medial fracture had significantly greater mean neointimal thickness than those without (1.37+/-0.68 compared with 0.81+/-0.47 mm(2); P<0.02). Neointimal inflammatory cell density correlated with increased neointimal thickness in patent vessels (r(2)=0.43, P<0.001). Immunostaining showed the total absence of ERs (oestrogen receptors), a poor cellular proliferative state as indicated by the presence of the Ki-67 marker, and persistent inflammation close to the stent wires as revealed by KP-1 and ACE (angiotensin-converting enzyme) immunostaining in most inflammatory cells in contact with the metal. These pathological findings may contribute to the more severe progression of disease and worse clinical outcome observed after conventional stented angioplasty of SVGs and might also interfere with the efficacy of drug-eluting stents in this specific atherosclerotic milieu. PMID- 17848139 TI - The epigenetic signature of CFTR expression is co-ordinated via chromatin acetylation through a complex intronic element. AB - The CFTR (cystic fibrosis transmembrane conductance regulator) gene is a tightly regulated and differentially expressed transcript in many mucosal epithelial cell types. It appears that DNA sequence variations alone do not explain CFTR-related gastrointestinal disease patterns and that epigenetic modifiers influence CFTR expression. Our aim was to characterize the native chromatin environment in cultured cells for intestinal CFTR expression by determining the relationship between histone acetylation and occupation of CFTR by multiple transcription factors, through a common regulatory element. We used HDAC (histone deacetylase) inhibition and ChIP (chromatin immunoprecipitation) analyses to define regions associated with acute acetylation of histone at the CFTR locus. We identified a region within the first intron associated with acute acetylation of histone H4 as an epigenetic signature corresponding to an intestine-specific enhancer element for CFTR. DHS (DNase I-hypersensitivity) assays and ChIP were used to specify control elements and occupation by regulatory factors. Quantitative ChIP procedures indicate that HNF1alpha (hepatic nuclear factor 1alpha) and Cdx2 (caudal homeobox protein 2) occupy and regulate through a novel intronic enhancer element of CFTR and that Tcf4 (T-cell factor 4) overlaps the same DNA element. RNAi (RNA interference) of Tcf4 and HNF1alpha decreased intestinal cell CFTR expression, identifying these as positive regulatory factors and CFTR as a target for Wnt signalling. We have linked the acetylation signature of nucleosomal histones to active intestinal CFTR expression and occupation by transcription factors HNF1alpha, Cdx2 and Tcf4 which converge to modify chromatin architecture. These studies suggest the therapeutic potential of histone modification strategies, such as inhibition of HDAC activity, to treat CFTR-associated disease by selectively enhancing CFTR expression. PMID- 17848141 TI - Editorial. PMID- 17848137 TI - Activation of G protein-coupled receptors: beyond two-state models and tertiary conformational changes. AB - Transformation of G protein-coupled receptors (GPCRs) from a quiescent to an active state initiates signal transduction. All GPCRs share a common architecture comprising seven transmembrane-spanning alpha-helices, which accommodates signal propagation from a diverse repertoire of external stimuli across biological membranes to a heterotrimeric G protein. Signal propagation through the transmembrane helices likely involves mechanistic features common to all GPCRs. The structure of the light receptor rhodopsin may serve as a prototype for the transmembrane architecture of GPCRs. Early biochemical, biophysical, and pharmacological studies led to the conceptualization of receptor activation based on the context of two-state equilibrium models and conformational changes in protein structure. More recent studies indicate a need to move beyond these classical paradigms and to consider additional aspects of the molecular character of GPCRs, such as the oligomerization and dynamics of the receptor. PMID- 17848142 TI - Impact of diet, physical activity, lipid status and glycoregulation in estimation of score (systematic coronary risk evaluation) for ten years in postmenopausal women. AB - The incidence of cardiovascular diseases (CVD) in women, although lower than in men, increases dramatically after the menopause. Diabetes mellitus is a more powerful predictor of CHD risk and prognosis in women than in men. The aim of this study was to promote diet and physical activity (PA) regimen in order to decrease coronary risk in next years in postmenopausal women with impaired glucose tolerance. Methodological approach of this research is to compare data gathered trough prospective and retrospective analysis of anamnestic data, clinical research, diagnostic tests and biochemical parameters of 100 examinees, regarding the glycoregulation, lipid status, body mass indexes, incidence of hypertension, uric acid and fibrinogen level. The SCORE (Systematic Coronary Risk Evaluation) assessment system is derived from a large dataset of prospective European studies and predicts any kind of fatal CVD events over a ten-year period. It was documented that the then year risk of fatal CVD exerted a shift toward the lower percent value in postmenopausal women after proposed diet/PA regimen. In pre-menopausal women the estimated ten year risk of fatal CVD by SCORE was shifted toward the level below 1%. The risk of 15% and above was not documented after diet/physical activity regimen. The prevalence of the atherogenic lipid markers at the beginning and the end of the assay decreased for all investigated lipid parameters in the group of pre-menopausal women what was more than in postmenopausal ones. Presented data indicate that dietary regimen and physical activity are crucial factors in CVD prevention throughout menopause and beyond. Behavioral changes aimed at decreasing food intake and increasing energy expenditure, should be implemented in pre-menopausal period of life. PMID- 17848144 TI - Troponin T and histological characteristics of rat myocardial infarction induced by isoproterenol. AB - In our investigation,we used short-time model of myocardial infarction of rats induced by high dose of isoproterenol (ISP). We investigated cardiac troponin T blood level (cTnT) and histological characteristics of rat myocardium. ISP, single, intraperitoneal dose 250 mg/kg was given to male, adult, Wistar rats (n=12). Rats were distributed depending on their body weight in subgroups: ISP I (BW 260-280g) and ISP II (BW 250-400g).Control group (n=9) was treated with intraperitoneal dose of 0,95% NaCl. Cardiac TnT was measured by electrochemiluminiscence (ECLA) sandwich immunoassay in rat serum 4 hours after ISP application. Rats' hearts were dissected and examined by qualitative histological method (HE). Statistical significance was set at 0,05. There was significant difference in cTnT of ISP II (p=0,0001) vs. control and ISP I (p<0,05) vs. control. Significant difference was between ISP I and ISP II subgroups (p<0.001). The accent of histological changes of myocardium was on nuclei of cell. Cells showed acidophilic changes and nuclei disappearance as signs of coagulative necrosis development. Extensivity of histological changes were different between ISP I and ISP II subgroup. Used dose of ISP induced development of myocardial necrosis in rats. Subendocardial portion of myocardium was more vulnerability than subepicardial portion. Rats of ISP II had more extensive histological changes than these in ISP I. Administered doses of ISP enabled cTnT utilization as a marker of myocardial necrosis. PMID- 17848143 TI - Non-small cell lung carcinoma: cyclin D1, bcl-2, p53, Ki-67 and HER-2 proteins expression in resected tumors. AB - The aim of this study was to investigate expression of cyclin D1, bcl-2, p53, Ki 67 and HER-2 proteins in 14 cases of non-small cell lung cancer and to establish their correlation to classical clinico-pathological findings, and alleged prognostic value to estimate biological potential of tumor. Retrospective pilot study of the surgically treated non-small cell lung cancer biopsy specimen, paraffin embedded, used immunohistochemical method to demonstrate expression of cyclin D1, bcl-2, p53, Ki-67 and HER-2. Protein quantification was performed by the semi-quantitative method. Achieved results were correlated with classical clinico-pathological parameters, like tumor size, histological type, differentiation level, presence of vascular invasion and metastasis in regional lymph nodes. Out of 14 cases of non-small cell lung cancer, squamous cell carcinoma was found in 7 patients, giant cell carcinoma in 3, adenocarcinoma in 2, and 1 case of pleomorphic and mucoepidermoid carcinoma. Expression of cyclin D1 was not found, while expression of HER-2 and bcl-2 protein was established in one cases each. p53 expression was noted in 8 cases (57,1%). Statistically positive significant correlation (p<0,05) was found among: presence of lymphovascular invasion to tumor tissue and appearance of nodal metastasis; proliferation Ki-67 index and level of tumor differentiation, i.e. size of tumor. Other investigated parameters showed no significant statistically dependence. p53 expression was not correlated to any of the investigated parameters what might imply the possibility that there is an independent pathway of this protein expression. Negative expression of bcl-2 protein points out to possibility that it is not included into process of tumor apoptosis, as well as that proteins cyclin D1 and HER-2 are not included into processes of the tumor genesis. Since the proliferative activity of the tumor, measured by the expression of Ki-67, is correlated to the gradus and size of the tumor mass, Ki-67 protein can be of a prognostic value to determine biological potential of non-small cell lung cancer. PMID- 17848145 TI - Hexagon TB for the rapid diagnosis of lung TBC in praxis. AB - Hexagon TB is intended for the rapid diagnostics of tuberculosis. Tuberculosis is a contagious and epidemic disease. According to the data published by WHO, 3-4 millions of patients are diagnosed with this disease annually. In 2004, 107 new cases were discovered in the area of Tuzla Municipality. Annual incidence of this disease is 62,9 per 100 000 inhabitants in Bosnia and Herzegovina; 28,9 in Slovenia; 33,2 in FYRM; 48,5 in Croatia; 41,8 in Serbia and Montenegro. Western European countries have a rather low rate of the disease--5-10 cases per 100 000 inhabitants. Efficiency of Hexagon TB examination method was tested on 100 patients. The subjects were patients with clinical symptoms of active TBC infection, persons who were in contact with TBC patients and persons earlier cured of TBC. All the subjects were tested with Hexagon TB, and the results were compared against lungs X-rays and sputum test for BK and LOW. Hexagon TB is intended for rapid, qualitative detection of IgG, IgA, IgM antibodies against M. tuberculosis and mycobacterium in human serum, plasma or whole blood as an aid in the early diagnostics of tuberculosis infections for professional use. Hexagon TB was positive in 11 of the examined patients. 10 patients had changes suggesting TBC. 1 patient was directly positive for BK and 3 patients were positive for LOW. Of all the examined patients, 3 were positive for all tests positive. According to our results, Hexagon TB has significant importance in practice of rapid TBC diagnostics compared to lungs X-ray and examination of sputum for BK and LOW. PMID- 17848146 TI - Comparison of trazodone, diazepame and dibenzepine influences on rat brain beta endorphins content. AB - The aim of our study was to establish the extent of influence of different psychotropic drugs to brain Beta-endorphins in experimental animals. The study was performed on albino Wistar rats (weight 250 g), treated with different psychoactive drugs. RIA technique was employed for quantification of brain beta endorphins. Brain beta-endorphins were higher in experiment group treated with trazodone (929 pg/g +/- 44,43; X+/-SD), and dibenzepine (906,63 pg/g +/- 74,06), yet with lower brain content in rats treated with diazepam (841,55 pg/g +/- 68,47), compared to brain beta-endorphins content of control group treated with saline solution (0,95% NaCl) (873,5 pg/g +/- 44,89). Significant differences were obtained comparing brain beta-endorphins of trazodone vs. diazepam treated animals, with diazepam group having lower values (p<0,02). This study showed differences in changes of rat brain beta-endorphins contents when different psychoactive drugs are used. Therefore, we consider that beta-endorphins could be used for evaluation of effects of psychoactive drugs, as a useful parameter in therapy with these psycho-pharmaceuticals. PMID- 17848147 TI - Frequency of feet deformities in pupils attending junior grades of elementary school. AB - The examination of feet by plantograph was performed in 552 pupils of first, second and fourth grades of elementary school "Harmani II" in Bihac. Examination revealed 201 children (36,42%) with satisfactory condition (pedes recti) while 351 pupils were diagnosed with certain form of feet deformity. Frequencies of feet deformities in girls are 60,00% in first, 65,19% in second and 66,30% in fourth grade. Average frequency of feet deformities in the examined girls is 64,90%. Pedes plani was found in 24,91% pupils. Frequencies of feet deformities in boys are 61,29% in first, 65,54% in second and 52,54% in fourth grade. Average frequency of feet deformities in the examined boys is 62,17%. Pedes plani is the most frequent deformity (23,83%). PMID- 17848148 TI - Electroneurography of right median and ulnar nerves in diabetic patients with and without retinopathy. AB - In this study we examined motor and sensory conduction velocities in right median and ulnar nerves in diabetic patients. Control group consisted of 25 healthy volunteers (13 males) with average age of 52 years. The first examined group consisted of 25 diabetic patients (13 males) without retinal changes, 59,6 years old on average, and the second group consisted of 40 patients (15 males) 59,4 years old on average: 22 of them with type 1, and 18 with type 2 retinal changes. The motor and sensory conduction velocities in right median nerve in the control group were significantly higher than those measured in the first group (p<0,0005 for motor, and p=0,0027 for sensory velocity), and the second group (p<0,0001 for motor, and p=0,0001 for sensory velocity). Significantly higher conduction velocities in sensory median nerve were compared between the examined groups (p<0,001), but motor conduction velocity was not significantly higher (p=0,09). The motor conduction velocity in ulnar nerve in the control group was significantly higher in comparison with the patients of first (p=0,0027) and second examined group (p=0,0001). The sensory conduction velocity in ulnar nerve was not significantly higher compared with the first (p=0,081), and significantly higher compared with the second examined group (p<0,0001). The sensory conduction velocity of ulnar nerve was significantly higher (p=0,019) in diabetic patients without retinopathy compared with patients with retinopathy. Diabetic patients with retinal changes have higher risk of developing more severe neurophysiologic signs of neuropathy. So, simple observation with ophthalmoscope may be useful diagnostic tool in its determination and may be the target of further therapeutic strategy. PMID- 17848149 TI - Using verapamil as protective factor in renal ischemia reperfusion injury during anatrophic nephrolithotomy. AB - Anatrophic nephrolithotomy (ANL) in the selected cases represents the method of choice in the treatment of staghorn calculi. We evaluated postoperative outcome of patients subjected to standard ANL that received 10 mg of Verapamil immediately before declamping renal artery, due to prevention of reperfusion injury. From 2002 to 2005, 18 nephrolithotomies were performed on 15 patients, in the Urology Clinic, University of Sarajevo Clinics Centre. Preoperative evaluation included intravenous urography and radionuclide renal scans which had been repeated 6 months after the operations. 10 males and 5 females were operated with mean age of 45 years. Urography and renal scans showed severe calyceal distortion and infundibular stenosis in 83% cases, complicated with ureteropelvic junction obstruction in 55% cases. Chronic kidney failure was present in 60% patients. Mean operative time was 150 minutes, with mean cold ischemia time of 61 minutes and mean blood loss of 300ml. There were five minor postoperative complications. Residual small calculi were found in 3 patients. Kidney function was stabilized in the patients suffering from chronic kidney failure, which was proved by radio nuclide imaging. ANL improved by using calcium channel blockers as a protective factor for reperfusion injury proved to be a good treatment choice with a low level of complications and noticeable stabilization and improvement of kidneys function. PMID- 17848150 TI - Evaluation of the preoperative stage and operative findings in patients with non small cell lung cancer. AB - Lung cancer is responsible for 40% mortalities from malignant diseases in man and exhibits an extremely infiltrating way of growing. It does not respect the lobes' or the organs' borders and spreads by blood system, lymph system and per continuitatem. According to its biological characteristics and response to treatments it may be divided in to small cell lung cancer (SCLC) and non small cell lung cancer (NSCLC), which also includes other histological types. Lung cancer treatment includes surgical treatment, chemotherapy, radiotherapy, the combination of the former three as well as symptomatic treatment. In this study, we analyzed 125 patients with lung cancer, that were hospitalized at the Clinic for Thoracic Surgery in KCU Sarajevo. The difference according to gender is statistically significant because we had 111 (88,8%) male patients in comparison with 14 (11,2%) female patients. The average age of male patients was 60,3 years while female patients were 61,9 years old on average. Thus, the difference in average age is not statistically significant. In diagnostic procedures: chest radiography was the most significant in peripheral lesions (60, 8%). CT of the thoracic organs has a statistical significance because the tumor changes were confirmed in 123 patients (98,4%). In bronchoscopy, we had 120 patients (96,0%). The number of patients with preformed lobectomy (63) is statistically significantly greater in the observed group (125) then the number of patients with other operative procedures preformed. From the postoperative complications we had exitus letalis 2 (1,6%), wound infection 19 (15,2%), and 104 without complications (83,2%). The results of testing the significance of differences according to the cancer types in non small cell lung cancer were planocellular, adenocarcinoma, and macrocellular. Comparing the preoperative staging and operative findings through stages we obtained to the following results: in stage ST0 the deviation was 16,7%, STIA the deviation was 40,1%, STIB the deviation was 16,1%, STIIA the deviation was 11,1%, STIIB the deviation was 12,5%, STIIIA the deviation was 33,33%, STIIIB the deviation was 33, 3%. From the overall number of patients, who were in preoperatively graded stage STIA, operative findings confirmed STIA, which makes the most important statistically significant difference. In 36 patients or 28,8% the status was changed in operative finding. In 89 patients preoperative status or 72,2% remained unchanged following the operation. PMID- 17848151 TI - Management of chronic nonbacterial prostatitis/chronic pelvic pain syndrome. AB - Chronic nonbacterial prostatitis/chronic pelvic pain syndrome is unsatisfactorily defined and insufficiently studied illness. Also, the treatment success is questionable and therefore, this illness is a therapeutical problem for urologists--which medications are the best choice in treating this uncomfortable condition? This paper presents results of prospective, open, analytical, comparative study that was performed on 90 patients with diagnosed chronic nonbacterial prostatitis/chronic pelvic pain syndrome. Patients were divided into three groups and were treated with two medications ciprofloxacin (C), doxazosin (D) and combination of ciprofloxacin + doxazosin (C+D). The effects were measured using symptom questionnaire for prostate illnesses of the National Institute for Health - USA (NIH-CPSI). During the basic evaluation, sum ranging from 0 to 43 was calculated for each patient. This number is called total sum NIH-CPSI (National Institutes of Health Chronic Prostatitis Symptom Index) of the questionnaire, which generates the questions from 1 to 9. The most significant change occurred in C+D group where the total sum changed from 18-38 in the beginning to 5-31 at the end of the treatment (55,1% (p<0,001)). Significant changes were also found in D group where the change was 46, 4% (p<0,001). At the end of the treatment no significant change was registered in C group (p<0,005): p<0,001--significance threshold. Combination of ciprofloxacin + doxazosin proved to be the best choice for treatment. PMID- 17848152 TI - Quality of life in stroke survivors under the sixty years of age. AB - The objective of the study was to analyze the quality of life six months after stroke in survivors under sixty years of age, to determine which life activities was the most affected, as well as to correlate the neurological insufficiency and the quality of life. It monitored 200 stroke survivors under sixty years of age treated at the Department of Neurology, University Clinical Centre Tuzla. Average age was 51,83 years (+/-7,02). The ischemic stroke was diagnosed in 77,5% stroke survivors, cerebral hemorrhage in 15%, and subarachnoid hemorrhage in 7,5%. Five stroke survivors suffered hemiplegia (2,5%), 24 (12%) experienced moderate consequences and 143 (71,5%) had mild consequences. No neurological deficit had 28 (14%) stroke survivors. Six months after the onset of disease all stroke survivors have been followed-up and evaluated about quality of life by filling in a modified questionnaire: Questionnaire on Quality of Life after Stroke (2). The questionnaire contained 20 questions covering four fields of life: Working Ability, Home Activity, Family Relations and Leisure Activities. Six months after the onset of stroke a worse quality of life in comparison to the period before the disease was noted in 172 (86%) stroke survivors, the unchanged in 19 (9,5%) and better in 9 (4,5%). The most affected is the field "Leisure Activities", followed by "Family Relations", "Home Activity", and the least affected is "Work Ability". The neurological deficit significantly correlates to the "Home Activities" and "Leisure Activities". PMID- 17848153 TI - 99m Tc-sestamibi scintimammography in detection of recurrent breast cancer. AB - The aim of this study was to asses the accuracy of 99mTc-sestamibi scintimammography in patients with suspected recurrent breast cancer in the breast or loco regional tissues. After routine analyses in twenty-eight women (clinical examination, ultrasound, X-ray mammography, and fine needle aspiration biopsy) they were examined by scintimammography. All patients with suspected recurrent cancer in the breast or loco regional tissues (19) undergone surgery and the final diagnosis was determined by histopathological examination. Another 9 patients were followed 6-24 months. The scintigraphic studies were correlated with radiological findings and/or with histopathology. There were 19 patients with recurrent tumours (15 with loco-regional recurrent and 4 in another breast). X-ray mammography identified 13 of these cancers. 99mTc-sestamibi scintimammography identified seventeen of recurrent breast cancers. In the seven out of nine patients without cancer, scintimammography were reported as having no changes consistent with cancer. X-ray mammography showed suspected cancer lesions in four out of nine patients without cancer. There were two false-positive scintimammograms and one false negative. Axillary lymph node recurrence occurred in four patients. All of them were positive on scintimammography. 99mTc-sestamibi scintimammography showed higher sensitivity, specificity and accuracy per patient than did X-ray mammography (90,9% vs. 63,6%, 71,4% vs. 57,1% and 83,3% vs. 61,1%, respectively). To identifying recurrent breast cancer disease is better to use scintimammography than X-ray mammography. PMID- 17848154 TI - Impact of education on disease knowledge and glycaemic control among type 2 diabetic patients in family practice. AB - In patients with diabetes type 2, good knowledge about disease often doesn't follow appropriate behavior in their life. Therefore, we wanted to find out basic level of disease knowledge and glycemic control among type 2 diabetic patients, and after that impact of passive and intensive education on knowledge and glycemic control. Starting with 130 participants, 91 patients with type 2 diabetes, from four family medicine services in Tuzla Canton, completed six months education about their disease. Disease Knowledge Test of Michigan Diabetes Training and Research Center was used to evaluate knowledge about diabetes and glycaemic control was assessed by HbA1c. Participants were tested at the beginning of survey, after 3 months of passive education and additional 3 months of intensive one. Basic test showed good knowledge of participants (score 8,3 out of 15), improved knowledge after passive education (score 9,23) and intensive one (11,19) (P<0,0001). Demographic characteristics of patients (age, sex, living area, level of education, duration of disease and type of treatment) had no influence on disease knowledge and glycaemic control during education. Generally, patient education improved significantly glycaemic control by HbA1c reduction 0,45% (P=0,011) without significant differences between passive and intensive one. Education of patients improves both disease knowledge and glycaemic control among type 2 diabetic patients. PMID- 17848155 TI - Empirical antibiotic therapy of sepsis in surgical intensive care unit. AB - Retrospective study was conducted in surgical intensive care unit (ICU) in Clinical Hospital Center Zagreb in 2005. The aim of study was to create guidelines for empirical antibiotic therapy of sepsis in ICU for unknown causative agent based on antimicrobial susceptibility of causative bacteria. Thirty-two patients with severe sepsis were included in study and from medical records their clinical and microbiological data were analyzed. Antimicrobial susceptibility of the strains isolated from the blood-culture was tested by disk diffusion method according to CLSI (Clinical Laboratory Standard Institution). We used APACHE II score to predict the severity of illness. Mann-Whitney test and chi2 test were used to test statistical significance difference between results. Acinetobacter baumannii and Pseudomonas aeruginosa were the predominant causative agent. Acinetobacter baumannii was displaying excellent susceptibility to ampicillin+sulbactam and carbapenems, whereas Pseudomonas aeruginosa was showed good susceptibility on ceftazidim and carbapenems. Methicillin-resistant Staphylococcus aureus (MRSA), third predominant causative agent exhibiting good susceptibility to vancomycin and linezolide. The recommended therapy is empirical antibiotic therapy and should cover all important pathogens. PMID- 17848156 TI - Macrosomic births at Mostar Clinical Hospital: a 2-year review. AB - The aim of this research was to determine the incidence, risk factors and perinatal outcome of the macrosomic infants (birth weight > or = 4000 g). The retrospective research was performed using a case-control study conducted at Mostar Clinical Hospital. Total of 379 women gave singleton term births to macrosomic newborn in the period from January 1st, 2004 to December 31st, 2005 (observed group). Another 379 singleton normal birthweight term newborns (birth weight < 4000 g, but not small for gestational age), of the same maternal parity and age, who were delivered in the same period, formed the control group. The incidence of macrosomic births was 13, 1%. In the study group, significantly higher number of cases of postdatism (> 42 weeks of gestation) (P<0,001), maternal obesity (prepregnancy BMI> 26 kg/m2) (P<0,001), gestational diabetes mellitus (P=0,033), hypertension (P=0,025) and male infant (P<0,001) were observed. Cesarean delivery (P<0,001), intrapartal complications (cephalopelvic disproportion P<0.001, perineal trauma P=0,042) and newborn birth trauma (clavicular fracture P=0,038, brachial palsy P=0,021) occurred significantly more often in the macrosomic group. There was only one fetal death in the macrosomic group. In the control group there were no cases of perinatal deaths. To conclude, it is important to emphasize the significance of proper diagnosis of fetal macrosomia and management of macrosomic birth, since we have seen a growing number of macrosomic births during the last decades, and have faced a problem of increased risks of adverse perinatal outcome. PMID- 17848157 TI - Transit time flowmetry in coronary surgery--an important tool in graft verification. AB - The aim of this study was to analyze the Transit time flow measurement (TTFM) experience in the first 1000 CABG operations. First 1000 patients had coronary artery bypass grafting (CABG) performed in Cardiovascular Clinic, University Clinical Centre Tuzla, Bosnia and Herzegovina, between September, 1998 and September, 2003. CABG without use of cardiopulmonary bypass (CPB)-(OPCAB) was used as the preferential surgical method both because this method is reported to have equal or better results than CABG with use of CPB (ONCAB), and because of the significant cost savings realized. TTFM was routinely used in all grafts as a quality assurance measure. Criteria for a poor functioning graft were: low mean flow (MF), pulsatility index (PI) above 5 and a poor diastolic flow pattern. When no reversible cause of poor TTFM results were identified the graft was revised. A total of 1394 grafts in OPCAB group and 1478 in ONCAB group were performed. A total of 38 grafts (2,72%) in 37 patients (7,07%) were revised in OPCAB group, and 26 grafts (1,75%) in 26 patients (5,45%) in ONCAB group. 1 patient in OPCAB group needed 2 graft revisions. Graft revisions were more common in OPCAB, but with no significant difference (p=0,1035). The most frequently revised graft was LAD graft in both groups. Although the percentage of grafts revised are relatively low, it is still very important to record TTFM. More than 5% of patients in both groups needed graft revision. Although TTFM does not guarantee that grafts will stay open for a prolonged period of time we certainly believe that grafts that are occluded at the time of surgery will continue to stay occluded. TTFM is especially critical in OPCAB surgery where the technical challenge of grafting is higher then in ONCAB. PMID- 17848158 TI - Effect of magnesium stearate concentration on dissolution properties of ranitidine hydrochloride coated tablets. AB - Most pharmaceutical formulations also include a certain amount of lubricant to improve their flowability and prevent their adhesion to the surfaces of processing equipment. Magnesium stearate is an additive that is most frequently used as a lubricant. Magnesium stearate is capable of forming films on other tablet excipients during prolonged mixing, leading to a prolonged drug liberation time, a decrease in hardness, and an increase in disintegration time. It is hydrophobic, and there are many reports in the literature concerning its adverse effect on dissolution rates. The objective of this study was to evaluate the effects of two different concentrations of magnesium stearate on dissolution properties of ranitidine hydrochloride coated tablet formulations labeled to contain 150 mg. The uniformity content was also checked. During the drug formulation development, several samples were designed for choice of the formulation. For this study, two formulations containing 0,77 and 1,1% of magnesium stearate added in the manufacture of cores were chosen. Fraction of ranitidine hydrochloride released in dissolution medium was calculated from calibration curves. The data were analyzed using pharmacopeial test for similarity of dissolution profiles ( f2 equation), previously proposed by Moore and Flanner. Application of f2 equation showed differences in time-course of ranitidine hydrochloride dissolution properties. The obtained values indicate differences in drug release from analyzed ranitidine hydrochloride formulations and could cause differences in therapeutic response. PMID- 17848159 TI - Design, morphometry and development of the secondary osteonal system in the femoral shaft of the rabbit. AB - The architecture of the diaphyseal bone is closely correlated with the cortical vessel network, whose pattern develops in the course of growth. Various methods have been applied to clarify the three-dimensional anatomy of the cortical canal system, but there is still disagreement about the geometry, blood supply, flux dynamics and factors controlling canal geometry during bone growth and remodeling. A modification of the currently employed dye-injection method was applied to study the vessel network of the whole hemi-shaft of the rabbit femur in mature bones (8-month-old rabbits) and growing bones (1.5-month-old rabbits). The cortical vascular tree of the hemi-shaft of the femur was injected with black China ink and observed in full-thickness specimens of the cortex. The same specimens were then processed for histology. A comparative study of the middle diaphysis (mid-shaft) with the distal extremity (distal shaft) was performed in both young and old rabbit femurs. The longitudinally oriented pattern of the vessel network was seen to develop in the diaphysis of mature femurs, while at the extremity of the shaft of the same specimen the network showed a reticular organization without a dominant polarization. The vessels were significantly higher in the mid-shaft than in the distal shaft of the old femurs (P < 0.0001), as was their diameter (P < 0.05). In the group of young rabbits at mid-shaft level the longitudinally oriented pattern of the vessel network was not yet completely developed, without their being significant differences in length and diameter between the mid-shaft and distal shaft. The differentiation of the mid shaft from the distal shaft was confirmed histologically by the presence, in the latter, of longitudinal calcified cartilage septa between osteons. This pattern of structural organization and development of the intracortical vascular network has not been previously reported. The cells primarily involved in polarization of the remodeling process were the osteoclasts at the top of the cutting cones advancing from the proximal and distal metaphyses toward the mid-shaft. This suggests, first, a relationship with the longitudinally oriented structures already present in the cortex near the metaphysis (the calcified cartilage septa) and then with the columns of interosteonic breccia, which were formed as a secondary effect of the longitudinal polarization of the remodeling process. Our observations did not enable us to substantiate the model of two different systems, one of longitudinal vessels (Havers) and the other of connecting transversal vessels (Volkmann), but suggested instead that there is a network whose loops lengthen in the direction of the major bone axis in the course of growth and secondary modeling. The associated morphology supported the view that the type of structural organization of the tubular bone cortex is primarily determined by an inherited constitutional factor rather than by mechanical strains. PMID- 17848160 TI - Gap junction protein expression and cellularity: comparison of immature and adult equine digital tendons. AB - Injury to the energy-storing superficial digital flexor tendon is common in equine athletes and is age-related. Tenocytes in the superficial digital flexor tendon of adult horses appear to have limited ability to respond adaptively to exercise or prevent the accumulation of strain-induced microdamage. It has been suggested that conditioning exercise should be introduced during the growth period, when tenocytes may be more responsive to increased quantities or intensities of mechanical strain. Tenocytes are linked into networks by gap junctions that allow coordination of synthetic activity and facilitate strain induced collagen synthesis. We hypothesised that there are reductions in cellular expression of the gap junction proteins connexin (Cx) 43 and 32 during maturation and ageing of the superficial digital flexor tendon that do not occur in the non injury-prone common digital extensor tendon. Cryosections from the superficial digital flexor tendon and common digital extensor tendon of 5 fetuses, 5 foals (1 6 months), 5 young adults (2-7 years) and 5 old horses (18-33 years) were immunofluorescently labelled and quantitative confocal laser microscopy was performed. Expression of Cx43 and Cx32 protein per tenocyte was significantly higher in the fetal group compared with all other age groups in both tendons. The density of tenocytes was found to be highest in immature tissue. Higher levels of cellularity and connexin protein expression in immature tendons are likely to relate to requirements for tissue remodelling and growth. However, if further studies demonstrate that this correlates with greater gap junctional communication efficiency and synthetic responsiveness to mechanical strain in immature compared with adult tendons, it could support the concept of early introduction of controlled exercise as a means of increasing resistance to later injury. PMID- 17848161 TI - The development of the neural crest in the human. AB - The first systematic account of the neural crest in the human has been prepared after an investigation of 185 serially sectioned staged embryos, aided by graphic reconstructions. As many as fourteen named topographical subdivisions of the crest were identified and eight of them give origin to ganglia (Table 2). Significant findings in the human include the following. (1) An indication of mesencephalic neural crest is discernible already at stage 9, and trigeminal, facial, and postotic components can be detected at stage 10. (2) Crest was not observed at the level of diencephalon 2. Although pre-otic crest from the neural folds is at first continuous (stage 10), crest-free zones are soon observable (stage 11) in Rh.1, 3, and 5. (3) Emigration of cranial neural crest from the neural folds at the neurosomatic junction begins before closure of the rostral neuropore, and later crest cells do not accumulate above the neural tube. (4) The trigeminal, facial, glossopharyngeal and vagal ganglia, which develop from crest that emigrates before the neural folds have fused, continue to receive contributions from the roof plate of the neural tube after fusion of the folds. (5) The nasal crest and the terminalis-vomeronasal complex are the last components of the cranial crest to appear (at stage 13) and they persist longer. (6) The optic, mesencephalic, isthmic, accessory, and hypoglossal crest do not form ganglia. Cervical ganglion 1 is separated early from the neural crest and is not a Froriep ganglion. (7) The cranial ganglia derived from neural crest show a specific relationship to individual neuromeres, and rhombomeres are better landmarks than the otic primordium, which descends during stages 9-14. (8) Epipharyngeal placodes of the pharyngeal arches contribute to cranial ganglia, although that of arch 1 is not typical. (9) The neural crest from rhombomeres 6 and 7 that migrates to pharyngeal arch 3 and from there rostrad to the truncus arteriosus at stage 12 is identified here, for the first time in the human, as the cardiac crest. (10) The hypoglossal crest provides cells that accompany those of myotomes 1-4 and form the hypoglossal cell cord at stages 13 and 14. (11) The occipital crest, which is related to somites 1-4 in the human, differs from the spinal mainly in that it does not develop ganglia. (12) The occipital and spinal portions of the crest migrate dorsoventrad and appear to traverse the sclerotomes before the differentiation into loose and dense zones in the latter. (13) Embryonic examples of synophthalmia and anencephaly are cited to emphasize the role of the neural crest in the development of cranial ganglia and the skull. PMID- 17848162 TI - Toll-like receptors and immune regulation: their direct and indirect modulation on regulatory CD4+ CD25+ T cells. AB - Regulatory CD4(+) CD25(+) T (Treg) cells with the ability to suppress host immune responses against self- or non-self antigens play important roles in the processes of autoimmunity, transplant rejection, infectious diseases and cancers. The proper regulation of CD4(+) CD25(+) Treg cells is thus critical for optimal immune responses. Toll-like receptor (TLR)-mediated recognition of specific structures of invading pathogens initiates innate as well as adaptive immune responses via antigen-presenting cells (APCs). Interestingly, new evidence suggests that TLR signalling may directly or indirectly regulate the immunosuppressive function of CD4(+) CD25(+) Treg cells in immune responses. TLR signalling may shift the balance between CD4(+) T-helper cells and Treg cells, and subsequently influence the outcome of the immune response. This immunomodulation pathway may therefore have potential applications in the treatment of graft rejection, autoimmune diseases, infection diseases and cancers. PMID- 17848163 TI - Interferon-gamma-dependent inhibition of late allergic airway responses and eosinophilia by CD8+ gammadelta T cells. AB - We have previously shown that CD8(+)gammadelta T cells decrease late allergic airway responses, airway eosinophilia, T helper 2 cytokine expression and increase interferon-gamma (IFN-gamma) expression. We hypothesized that the effects of CD8(+)gammadelta T cells were IFN-gamma mediated. Brown Norway rats were sensitized to ovalbumin on day 1. Cervical lymph node CD8(+)gammadelta T cells from sensitized animals were treated with antisense oligodeoxynucleotide (5 micromol/l) to inhibit IFN-gamma synthesis or control oligodeoxynucleotide and 3.5 x 10(4) CD8(+)gammadelta T cells were injected intraperitoneally into sensitized recipients on day 13. Rats were challenged with aerosolized ovalbumin on day 15 and lung resistance was monitored over an 8 hr period, after which bronchoalveolar lavage was performed. Control oligodeoxynucleotide treated gammadelta T cells decreased late airway responses and eosinophilia in bronchoalveolar lavage. There was a complete recovery of late airway responses and a partial recovery of airway eosinophilia in recipients of antisense oligodeoxynucleotide treated cells. Macrophage ingestion of eosinophils was frequent in rats administered gammadeltaT cells but reduced in recipients of antisense oligodeoxynucleotide treated cells. These results indicate that CD8(+)gammadelta T cells inhibit late airway responses and airway eosinophilia through the secretion of IFN-gamma. Defective or altered gammadelta T-cell function may account for some forms of allergic asthma. PMID- 17848164 TI - Human dendritic cells transfected with allergen-DNA stimulate specific immunoglobulin G4 but not specific immunoglobulin E production of autologous B cells from atopic individuals in vitro. AB - Atopic/allergic diseases are characterized by T helper 2 (Th2)-dominated immune responses resulting in immunoglobulin E (IgE) production. DNA-based immunotherapies have been shown to shift the immune response towards Th1 in animal models. In further studies we showed that human dendritic cells (DC) transfected with allergen-DNA are able to stimulate autologous CD4(+) T cells from atopic individuals to produce Th1 instead of Th2 cytokines and to activate interferon-gamma (IFN-gamma)-producing CD8(+) T cells. The aim of this study was to analyse whether DC transfected with allergen-DNA are also able to influence immunoglobulin production of B cells from atopic donors. For this purpose, human monocyte-derived DC from grass-pollen allergic donors were transfected with an adenovirus encoding the allergen Phleum pratense 1 and cocultured with B cells, autologous CD4(+) T cells, and CD40 ligand-transfected L-cells. B cells receiving help from CD4(+) T cells stimulated with allergen-transfected dendritic cells produced more allergen-specific IgG4 compared to stimulation with allergen protein pulsed DC or medium, while total IgG4 production was not affected. In contrast, specific IgE production was not enhanced by stimulation with allergen DNA transfected DC compared to medium and inhibited compared to allergen protein pulsed DC with similar effects on total IgE production in vitro. Allergen-DNA transfected dendritic cells are able to direct the human allergic immune response from Th2-dominance towards Th1 and Tc1 also resulting in decreased IgE and increased IgG4 production. PMID- 17848167 TI - Coxsackievirus B3 activates nuclear factor kappa B transcription factor via a phosphatidylinositol-3 kinase/protein kinase B-dependent pathway to improve host cell viability. AB - Coxsackievirus B3 (CVB3) is the most common viral infectant of heart muscle. CVB3 directly injures cardiomyocytes. We have previously reported on a regulatory role for the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) pathway during CVB3 infection. Yet, the mechanism underlying this regulatory role has not been elucidated. The PI3K/Akt pathway is involved in various cellular processes and exerts its function through the activation of several downstream effectors. Among them, nuclear factor kappa B (NFkappaB) transcription factor is involved in inflammation, survival and apoptosis. In this study, we investigated the role of NFkappaB as a potential downstream mediator of signals through the PI3K/Akt cascade, in regulating CVB3-induced cellular injury. We report that CVB3 infection induces the translocation of NFkappaB into the nucleus of infected cells. Inhibition of the PI3K/Akt pathway markedly decreases virus-induced NFkappaB activation. Further, NFkappaB inhibition significantly suppresses host viability, suggesting a pro-survival role for NFkappaB. Short-term treatment of cells with tumour necrosis factor-alpha (TNF-alpha), a potent activator of NFkappaB, promotes host cell viability without affecting virus replication. However, a prolonged treatment has a detrimental effect on cells, indicating the existence of a delicate balance between the anti- and pro-apoptotic roles of TNF alpha in the setting of CVB3 infection. PMID- 17848165 TI - Corticosterone impairs dendritic cell maturation and function. AB - Dendritic cells (DC) play a critical role in initiating and directing adaptive immune responses against pathogens and tumours. Immature DC are thought to act as sentinels in peripheral tissues where their main function is to capture antigen at sites of infection, whereas mature DC are highly efficient at priming T-cell mediated immune responses against infectious pathogens. The DC maturation process is thought to be an important step in the efficient generation of cytotoxic T lymphocytes (CTL). It is well established that many aspects of immune function, including CTL-mediated antiviral immunity, are modulated by neuroendocrine derived products. Corticosterone (CORT), an adrenal hormone produced at increased concentrations during a stress response, has been shown to play a role in impaired CTL responses in stressed animals, leading to high mortality in mice normally resistant to viral infection. While direct effects of neuroendocrine mediators on CTL have been studied, little is known about their effects on DC that are critical for CTL priming. Here, we found that physiologically relevant concentrations of CORT, acting via the glucocorticoid receptor, functionally compromise DC maturation. DC exposed to CORT remained phenotypically and functionally immature after stimulation with lipopolysaccharide and were impaired for the production of interleukin (IL)-6, IL-12, and tumour necrosis factor alpha. These effects were biologically significant, as CORT treatment resulted in a marked reduction in the ability of DC to prime naive CD8(+) T cells in vivo. These findings offer a potential mechanism underlying stress-associated immunosuppression. PMID- 17848168 TI - The Mcf1 toxin induces apoptosis via the mitochondrial pathway and apoptosis is attenuated by mutation of the BH3-like domain. AB - Photorhabdus are Gram-negative, nematode-vectored bacteria that produce toxins to kill their insect hosts. The expression of one of these, Makes caterpillars floppy 1 (Mcf1), is sufficient to allow Escherichia coli to survive within, and kill, caterpillars which are otherwise able to clear E. coli infection. Mcf1 treated caterpillars show rapid loss of body turgor (the 'floppy' phenotype) and death is associated with massive apoptosis of both the midgut epithelium and insect phagocytes. Mammalian tissue culture cells treated with Mcf1 also display key features of apoptosis including zeiosis, apoptotic nuclear morphology, DNA laddering, activation of the effector caspase-3 and PARP cleavage. As Mcf1 carries a single BH3-like domain, here we investigate the hypothesis that this toxin promotes apoptosis via the mitochondrial pathway by mimicking a BH3 domain only protein. Consistent with this hypothesis, a double mutant within the BH3 like domain causes a dramatic decline in apoptosis. Mcf1 also alters mitochondrial membrane potential and triggers the release of cytochrome c. Cells overexpressing Bcl-x(L), an anti-apoptotic Bcl-2 family member, are resistant to Mcf1-mediated apoptosis, as are cells deficient in Bax. In addition, translocation of Bax to the mitochondrion is observed in response to Mcf1 treatment. Together, these results show that Mcf1 mediates apoptosis via the mitochondrial pathway, and are consistent with the hypothesis that the BH3-like domain in Mcf1 is a functional requirement for the pro-apoptotic activity of Mcf1. PMID- 17848169 TI - The carboxyl-terminal SH3 domain of the mammalian adaptor CrkII promotes internalization of Listeria monocytogenes through activation of host phosphoinositide 3-kinase. AB - The intracellular bacterial pathogen Listeria monocytogenes causes food-borne illnesses leading to gastroenteritis, meningitis or abortion. Listeria induces its internalization into some mammalian cells through binding of the bacterial surface protein InlB to its host receptor, the Met Receptor Tyrosine Kinase. InlB induced activation of Met stimulates host signal transduction pathways that culminate in cell surface changes driving pathogen engulfment. One mammalian protein with the potential to couple Met to downstream signalling is the adaptor CrkII. CrkII contains an unusual carboxyl-terminal SH3 domain (SH3C) that promotes entry of Listeria. However, binding partners or downstream effectors of SH3C remain unknown. Here, we use RNA interference and overexpression studies to demonstrate that SH3C affects bacterial uptake, at least in part, through stimulation of host phosphatidylinositide (PI) 3-kinase. Experiments with latex beads coated with InlB protein indicated that one potential role of SH3C and PI 3 kinase is to promote changes in the F-actin cytoskeleton necessary for particle engulfment. Taken together, our results indicate that the CrkII SH3C domain engages a cellular ligand that regulates PI 3 kinase activity and host cell surface rearrangements. PMID- 17848173 TI - Non-invasive measurement of the mean alveolar O(2) tension from the oxygen uptake versus tidal volume curve. AB - AIMS: The classical equations for measuring the mean and the ideal alveolar O(2) tension are based on assumptions, which are shown to be invalid. So we thought to develop a new, non-invasive method for measuring the mean alveolar P,O(2) within the volume domain (PA,O(2(Bohr))). This method is based on the oxygen uptake vs. tidal volume curve (VO(2) vs. VT) obtained during tidal breathing of room air and/or air enriched with oxygen. METHODS: PA,O(2(Bohr)) and the ideal alveolar PO(2) (PA,O(2(ideal))) were simultaneously measured in 10 healthy subjects and 34 patients suffering from chronic obstructive pulmonary disease (COPD) breathing tidally room air at rest. Additionally, 10 subjects (three healthy subjects and seven COPD patients) were studied while breathing initially room air and subsequently air enriched with oxygen. RESULTS: According to the results, PA,O(2(Bohr)) considerably differed from PA,O(2(ideal)) (P = 0.004). The cause of the difference, at the individual's R, is: (1) the difference between the arterial and Bohr's alveolar CO(2) tension, mainly in COPD patients, and (2) the inequality between Bohr's alveolar part of the tidal volume for CO(2) and O(2). Furthermore, end-tidal gas tension (PET,CO(2) and PET,O(2)) differed from Pa,CO(2) and PA,O(2(Bohr)) respectively. CONCLUSION: The deviation of PA,O(2(Bohr)) from PA,O(2(ideal)) has a definite impact on Bohr's dead space ratio for O(2) and CO(2), and on the alveolar-arterial O(2) difference. The difference (PA,O(2(Bohr)) - PA,O(2(ideal))) is not related to the pathology of the disease. So, gas exchange within the lungs should be assessed at the subject's R from PA,O(2(Bohr)) and PA,CO(2(Bohr)) but not from PA,O(2(ideal)) nor Pa,CO(2). PMID- 17848174 TI - SWOT analysis of Banff: strengths, weaknesses, opportunities and threats of the international Banff consensus process and classification system for renal allograft pathology. AB - The Banff process defined the diagnostic histologic lesions for renal allograft rejection and created a standardized classification system where none had existed. By correcting this deficit the process had universal impact on clinical practice and clinical and basic research. All trials of new drugs since the early 1990s benefited, because the Banff classification of lesions permitted the end point of biopsy-proven rejection. The Banff process has strengths, weaknesses, opportunities and threats (SWOT). The strength is its self-organizing group structure to create consensus. Consensus does not mean correctness: defining consensus is essential if a widely held view is to be proved wrong. The weaknesses of the Banff process are the absence of an independent external standard to test the classification; and its almost exclusive reliance on histopathology, which has inherent limitations in intra- and interobserver reproducibility, particularly at the interface between borderline and rejection, is exactly where clinicians demand precision. The opportunity lies in the new technology such as transcriptomics, which can form an external standard and can be incorporated into a new classification combining the elegance of histopathology and the objectivity of transcriptomics. The threat is the degree to which the renal transplant community will participate in and support this process. PMID- 17848170 TI - The chemokine network. II. On how polymorphisms and alternative splicing increase the number of molecular species and configure intricate patterns of disease susceptibility. AB - In this second review on chemokines, we focus on the polymorphisms and alternative splicings and on their consequences in disease. Because chemokines are key mediators in the pathogenesis of inflammatory, autoimmune, vascular and neoplastic disorders, a large number of studies attempting to relate particular polymorphisms of chemokines to given diseases have already been conducted, sometimes with contradictory results. Reviewing the published data, it becomes evident that some chemokine genes that are polymorphic have alleles that are found repeatedly, associated with disease of different aetiologies but sharing some aspects of pathogenesis. Among CXC chemokines, single nucleotide polymorphisms (SNPs) in the CXCL8 and CXCL12 genes stand out, as they have alleles associated with many diseases such as asthma and human immunodeficiency virus (HIV), respectively. Of CC chemokines, the stronger associations occur among alleles from SNPs in CCL2 and CCL5 genes and a number of inflammatory conditions. To understand how chemokines contribute to disease it is also necessary to take into account all the isoforms resulting from differential splicing. The first part of this review deals with polymorphisms and the second with the diversity of molecular species derived from each chemokine gene due to alternative splicing phenomena. The number of molecular species and the level of expression of each of them for every chemokine and for each functionally related group of chemokines reaches a complexity that requires new modelling algorithms akin to those proposed in systems biology approaches. PMID- 17848175 TI - A role for transportin in the nuclear import of adenovirus core proteins and DNA. AB - Adenoviruses target their double-stranded DNA genome and its associated core proteins to the interphase nucleus; this core structure then enters through the nuclear pore complex. We have used digitonin permeabilized cell import assays to study the cellular import factors involved in nuclear entry of virus DNA and the core proteins, protein V and protein VII. We show that inhibition of transportin results in aberrant localization of protein V and that transportin is necessary for protein V to accumulate in the nucleolus. Furthermore, inhibition of transportin results in inhibition of protein VII and DNA import, whereas disruption of the classical importin alpha-importin beta import pathway has little effect. We show that mature protein VII has different import preferences from the precursor protein, preVII from which it is derived by proteolytic processing. While bacterially expressed glutathione S-transferase (GST)-preVII primarily utilizes the pathway mediated by importin alpha-importin beta, bacterially expressed GST-VII favours the transportin pathway. This is significant because while preVII is important during viral replication and assembly only mature VII is available during viral DNA import to a newly infected cell. Our results implicate transportin as a key import receptor for the nuclear localization of adenovirus core. PMID- 17848176 TI - Heritability of flow-mediated dilation: a twin study. AB - BACKGROUND: Endothelial dysfunction assessed by brachial artery flow-mediated dilation (FMD) is a marker for early atherosclerotic vascular disease and future cardiovascular events. OBJECTIVE: To estimate the heritability of brachial artery FMD using a twin design. METHODS: We estimated the heritability of FMD using 94 middle-aged male twin pairs. FMD was measured by ultrasound, and traditional coronary heart disease risk factors were measured. Genetic modeling techniques were used to determine the relative contributions of genes and environment to the variation in FMD. RESULTS: The mean age of the twin participants was 54.9 +/- 2.8 years. The mean FMD was 0.047 +/- 0.030. The intraclass correlation coefficient was higher in MZ twins [0.38, 95% confidence interval (CI) 0.32-0.43] than in DZ twins (0.19, 95% CI 0.11-0.26), suggesting a role of genetic influence in FMD variation. Structural equation modeling showed that both genetic and unique environmental factors contributed significantly to the variation in FMD. The crude FMD heritability was 0.37 (95% CI 0.15-0.54). After adjustment for traditional cardiovascular risk factors, including age, total cholesterol, blood pressure, and body mass index, the heritability of FMD was 39% (95% CI 0.18 0.56). The remaining variation in FMD could be explained by individual-specific environment. CONCLUSION: This is the first study using twins to estimate the relative contributions of genetics and environment to the variation in FMD in a US population. Our results demonstrate a moderate genetic effect on brachial artery FMD, independent of traditional coronary risk factors. Our data also highlight the importance of unique environment on the variability in FMD. PMID- 17848177 TI - Tissue factor induction by protease-activated receptor 1 requires intact caveolin enriched membrane microdomains in human endothelial cells. AB - BACKGROUND: Protease-activated receptors (PARs) comprise a family of G-protein coupled receptors with a unique mechanism of proteolytic activation. PARs regulate a broad range of cellular functions and are active in the pathogenesis of disorders characterized by chronic inflammation or activation of the coagulation cascade. Signaling through PAR1 and PAR2 shifts the endothelium towards a prothrombotic phenotype, thereby exacerbating the initial pathophysiologic condition. OBJECTIVES: This study aimed to analyze the localization of PARs in the cell membrane and how their compartmentalization affects tissue factor (TF) in human endothelial cells. METHODS: TF expression was determined by quantitative real-time polymerase chain reaction analysis and by activity assays. The interaction of PARs with caveolin was investigated through: (i) caveolin-1 gene knockdown performed by transfection with specific small interfering RNA (siRNA); (ii) caveolin-enriched membrane microdomain disruption; and (iii) coimmunoprecipitation assay. RESULTS: We have shown that PAR1, but not PAR2, is present in endothelial caveolin-enriched membrane microdomains, where it is bound to caveolin-1, and that these structures must be intact if PAR1-induced signaling is to increase TF activity. Cholesterol depletion of endothelial cells by cholesterol-sequestering agents caused the PAR1 to relocate to high-density membranes, and impaired the induction of TF (P < 0.01) without affecting the PAR2 mediated procoagulant effect. In addition, siRNA directed against caveolin-1 inhibited TF activation by PAR1 (P < 0.01 and P < 0.01, respectively). CONCLUSIONS: PAR1 localization in the caveolin-enriched membrane microdomain, bound to caveolin-1, represents a crucial requirement for TF induction in endothelial cells. PMID- 17848178 TI - Post-translational modifications regulate matrix Gla protein function: importance for inhibition of vascular smooth muscle cell calcification. AB - BACKGROUND: Matrix Gla protein (MGP) is a small vitamin K-dependent protein containing five gamma-carboxyglutamic acid (Gla) residues that are believed to be important in binding Ca(2+), calcium crystals and bone morphogenetic protein. In addition, MGP contains phosphorylated serine residues that may further regulate its activity. In vivo, MGP has been shown to be a potent inhibitor of vascular calcification; however, the precise molecular mechanism underlying the function of MGP is not yet fully understood. METHODS AND RESULTS: We investigated the effects of MGP in human vascular smooth muscle cell (VSMC) monolayers that undergo calcification after exposure to an increase in Ca(2+) concentration. Increased calcium salt deposition was found in cells treated with the vitamin K antagonist warfarin as compared to controls, whereas cells treated with vitamin K(1) showed decreased calcification as compared to controls. With conformation specific antibodies, it was confirmed that warfarin treatment of VSMCs resulted in uncarboxylated (Gla-deficient) MGP. To specifically test the effects of MGP on VSMC calcification, we used full-length synthetic MGP and MGP-derived peptides representing various domains in MGP. Full length MGP, the gamma-carboxylated motif (Gla) (amino acids 35-54) and the phosphorylated serine motif (amino acids 3-15) inhibited calcification. Furthermore, we showed that the peptides were not taken up by VSMCs but bound to the cell surface and to vesicle-like structures. CONCLUSIONS: These data demonstrate that both gamma-glutamyl carboxylation and serine phosphorylation of MGP contribute to its function as a calcification inhibitor and that MGP may inhibit calcification via binding to VSMC-derived vesicles. PMID- 17848180 TI - Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage: a cost-effectiveness analysis. AB - BACKGROUND: Erythromycin is a potent stimulator of gastrointestinal motility. Recent studies have examined the use of intravenous erythromycin to clear the stomach of blood before oesophago-gastroduodenoscopy (EGD) for acute upper gastrointestinal haemorrhage (UGIH). These studies have shown clinical effectiveness. AIM: To evaluate the cost-effectiveness of this intervention. METHODS: We sought to determine the cost-effectiveness of erythromycin before EGD from the payer's perspective. We found three relevant studies of erythromycin and used these data for the analysis. We obtained costs for intravenous erythromycin and charges for peptic ulcer hospitalization, EGD, surgery, and angiographic embolization. Complication rates were also incorporated from the literature. We implemented a model of health-related quality of life to measure the impact of the intervention. We created a decision-analysis tree and performed a probabilistic sensitivity analysis. RESULTS: A strategy of erythromycin prior to EGD resulted in a cost-effective outcome in a majority of trials using willingness-to-pay figures of USD 0, USD 50,000 and USD 100,000 per quality adjusted life-year (QALY). CONCLUSION: Because of the implications for cost saving and increase in QALY, we would recommend giving erythromycin prior to EGD for UGIH. PMID- 17848179 TI - Chronic plasminogen activator inhibitor-1 (PAI-1) overexpression dampens CD25+ lymphocyte recruitment after lipopolysaccharide endotoxemia in mouse lung. AB - BACKGROUND: Plasma plasminogen activator inhibitor-1 (PAI-1) level rises during sepsis and confers a worse prognosis. PAI-1 participation to sepsis has been poorly documented and was mainly associated with fibrin deposits. Beside fibrin deposits, increased tissue PAI-1 expression may contribute to the poor outcome of endotoxemia through other mechanisms. OBJECTIVE AND METHODS: During lipopolysaccharide (LPS) challenge, the role of PAI-1 in the early phase of inflammation was examined in the lungs of transgenic mice that either overexpress or lack the PAI-1 gene (PAI-1Tg or PAI-1(-/-)). RESULTS: Analysis of leukocytes revealed that neutrophil and macrophage infiltrations did not differ for PAI-1Tg and wild-type (WT) mice. Remarkably, CD25+ lymphocyte infiltration was totally blunted in PAI-1Tg lungs and inversely correlated with fibrin depositions. In parallel, mRNA levels of the regulatory T cell (Treg) markers FoxP3, CTLA-4, and GITR were significantly lower in PAI-1Tg than in WT lungs after LPS challenge. These data are supported by opposite results in PAI-1(-/-) lungs. The systemic compartments (spleen and peripheral blood) showed no decrease in CD25+, CD4+ CD25+ lymphocytes, and Treg markers in PAI-1Tg mice after LPS injection compared with WT mice. In addition, plasma and lung concentrations of interleukin-6 (IL-6) and macrophage inflammatory protein-1alpha (MIP-1alpha) were significantly higher in PAI-1Tg mice than WT mice. CONCLUSION: Our results suggest that chronic tissue PAI-1 overexpression influences the early phase of the inflammatory response during endotoxemia through the control of T lymphocyte traffic. PMID- 17848181 TI - Early versus late surgery for ileo-caecal Crohn's disease. AB - BACKGROUND: Surgical resection is almost inevitable in Crohn's disease. Surgery is usually performed for refractory or complicated disease: no studies appear to have been carried out, so far, to evaluate the potential benefits of performing surgery early in the course of the disease. AIM: To compare the long-term course of Crohn's disease following ileo-caecal resection performed at the time of diagnosis (early surgery) or during the course of the disease (late surgery). Patients and methods Overall 207 patients with ileo-caecal Crohn's disease at their first resection were reviewed: 83 patients underwent surgery at the time of diagnosis (early surgery), while 124 underwent surgery 54.2 months (range 1-438) after diagnosis (late surgery). The mean follow-up after surgery was 147 months (range 12-534). The primary endpoint was clinical recurrence, defined as need for corticosteroids for symptomatic disease in the presence of endoscopic and/or radiologic recurrence. Secondary endpoints were need for immunosuppressants and surgical recurrence. STATISTICAL ANALYSIS: Kaplan-Meier survival method and Cox proportional hazards regression model. RESULTS: Within 10 years after surgery, the cumulative probability of clinical recurrence was significantly lower in the early surgery group (Log Rank test P = 0.01). A trend was observed regarding the need for immunosuppressants (P = 0.05). No difference was observed regarding surgical recurrence. At multivariate analysis, early surgery was the only independent variable associated with a reduced risk of clinical recurrence (Hazard ratio, HR = 0.57; 95% CI 0.35 to 0.92, P = 0.02), but not with need for immunosuppressants and surgical recurrence (HR = 0.51; 95% CI 0.20 to 1.30, P = 0.15; HR = 0.66; 95% CI 0.33 to 1.35, P = 0.25, respectively). CONCLUSION: Early surgery prolongs clinical remission compared to surgery performed during the course of the disease, but the natural history of disease is not modified. PMID- 17848182 TI - Individualized population pharmacokinetic model with limited sampling for cyclosporine monitoring after liver transplantation in clinical practice. AB - BACKGROUND: We recently developed and validated limited sampling models (LSMs) for cyclosporine monitoring after orthotopic liver transplantation based on individualized population pharmacokinetic models with Bayesian modelling. Aim To evaluate LSM in practice, and to seek optimal balance between benefit and discomfort. METHODS: In 30 stable patients, more than 6 months after orthotopic liver transplantation, previously switched from trough- to 2 h post-dose (C2) monitoring, we switched to 3-monthly LSM 0,1,2,3 h-monitoring. During 18 months we evaluated dose, creatinine clearance, calculated area under the curve, intra patient pharmacokinetic variability and ability to assess systemic exposure by several previously validated LSMs. RESULTS: Within patients, there was variability of cyclosporine-area under the curve with the same dose (CV of 15%). Compared to C2-monitoring, there was no significant difference in dose (P = 0.237), creatinine clearance (P = 0.071) and number of rejections. Some models showed excellent correlation and precision with LSM 0,1,2,3 h comparing area under the curves (0,2 h: r(2) = 0.88; 0,1,3 h: r(2) = 0.91; 0,2,3 h: r(2) = 0.92, all P < 0.001) with no difference in advised dose. CONCLUSIONS: The limited sampling model, with only trough- and 2-h sampling, yields excellent accuracy and assesses systemic exposure much better than C2 with less bias and greater precision. Considering the calculated intra-patient variability, more precision is redundant, so LSM 0,2 h seems the optimal way of cyclosporine-monitoring. PMID- 17848183 TI - Colonic stent versus surgery for the management of acute malignant colonic obstruction: a decision analysis. AB - BACKGROUND: Acute colonic obstruction because of advanced colonic malignancy is a surgical emergency. AIM: To compare the clinical outcomes and cost-effectiveness of endoscopic self-expanding metal stent (SEMS) vs. surgery for emergent management of acute malignant colonic obstruction in patients with metastatic colorectal cancer over a 6-month period. METHODS: Decision analysis was used to calculate the cost-effectiveness and success of two competing strategies in a hypothetical patient with metastatic colon cancer presenting with acute, malignant colonic obstruction: (i) emergent colonic stent (SEMS cohort); (ii) emergent surgical resection followed by diversion (surgery cohort). RESULTS: Self expanding metal stent resulted in a success and a lower mortality rate when compared to surgery over a 6-month period. Colonic SEMS was also associated with a lower mean cost per patient (USD 27,225 vs. USD 57,398). Mortality in the surgery group was 25 times that of the SEMS cohort. One- and two-way sensitivity analyses identified SEMS as the dominant strategy. CONCLUSION: Colonic stent insertion is more effective and less costly than surgery for the management of colonic obstruction in patients with metastatic colon cancer. PMID- 17848185 TI - A novel approach to detect hot-spots in large-scale multivariate data. AB - BACKGROUND: Progressive advances in the measurement of complex multifactorial components of biological processes involving both spatial and temporal domains have made it difficult to identify the variables (genes, proteins, neurons etc.) significantly changed activities in response to a stimulus within large data sets using conventional statistical approaches. The set of all changed variables is termed hot-spots. The detection of such hot spots is considered to be an NP hard problem, but by first establishing its theoretical foundation we have been able to develop an algorithm that provides a solution. RESULTS: Our results show that a first-order phase transition is observable whose critical point separates the hot-spot set from the remaining variables. Its application is also found to be more successful than existing approaches in identifying statistically significant hot-spots both with simulated data sets and in real large-scale multivariate data sets from gene arrays, electrophysiological recording and functional magnetic resonance imaging experiments. CONCLUSION: In summary, this new statistical algorithm should provide a powerful new analytical tool to extract the maximum information from complex biological multivariate data. PMID- 17848186 TI - A longitudinal study on the occurrence of Cryptosporidium and Giardia in dogs during their first year of life. AB - BACKGROUND: The primary aim of this study was to obtain more knowledge about the occurrence of Cryptosporidium and Giardia in young dogs in Norway. The occurrence of these parasites was investigated in a longitudinal study by repeated faecal sampling of dogs between 1 and 12 months of age (litter samples and individual samples). The dogs were privately owned and from four large breeds. Individual faecal samples were collected from 290 dogs from 57 litters when the dogs were approximately 3, 4, 6, and 12 months old. In addition, pooled samples were collected from 43 of the litters, and from 42 of the mother bitches, when the puppies were approximately 1 and/or 2 months old. METHODS: The samples were purified by sucrose gradient flotation concentration and examined by immunofluorescent staining. RESULTS: 128 (44.1%) of the young dogs had one or more Cryptosporidium positive samples, whilst 60 (20.7%) dogs had one or more Giardia positive samples. The prevalence of the parasites varied with age. For Cryptosporidium, the individual prevalence was between 5.1% and 22.5%, with the highest level in dogs < 6 months old, and declining with age. For Giardia, the individual prevalence was between 6.0% and 11.4%, with the highest level in dogs > 6 months old, but the differences between age groups were not statistically significant. Significant differences in prevalences were found in relation to geographic location of the dogs. Both parasites occurred at low prevalences in Northern Norway. CONCLUSION: Both Cryptosporidium and Giardia are common in Norwegian dogs, with Cryptosporidium more prevalent than Giardia. Prevalences of the parasites were found to be influenced by age, geographical location, and infection status before weaning. PMID- 17848187 TI - Quantitative gait analysis as a method to assess mechanical hyperalgesia modulated by disease-modifying antirheumatoid drugs in the adjuvant-induced arthritic rat. AB - In the present study, azothioprine, chloroquine, D-penicillamine, methotrexate and sodium aurothiomalate (gold salt) were evaluated for possible disease modifying effects in the adjuvant-induced arthritis model of human rheumatoid arthritis in rats. Gait analysis was used to examine the role of disease modifying antirheumatic drugs in the development of pain. Body weights were also measured to monitor the progression of disease and the systemic antiarthritic effects of the test compounds used in this study, as well as their systemic toxicity. Our results showed that azothioprine (5 mg/kg/day), chloroquine (12.5 mg/kg/day), sodium aurothiomalate (2.5 mg/kg/day) and methotrexate (1 mg/kg/week) not only inhibited the macroscopic changes such as erythema and swelling of limbs, but also exhibited significant reversal of gait deficits seen in the untreated or saline-treated arthritic rats. No reduction in the body weights were observed in the arthritic rats treated with azothioprine, chloroquine, sodium aurothiomalate and methotrexate. D-Penicillamine (12.5 mg/kg/day), however, showed a significant reduction (P < 0.03) in the body weights of the arthritic rats over a period of 22 days; furthermore, it was unable to show any reduction in arthritic score (P < 0.1). In earlier experiments, chloroquine and methotrexate failed to suppress carageenan-induced edema, suggesting that the mode of antiarthritic action may be different from those of nonsteroidal anti inflammatory agents. Since these disease-modifying antirheumatic drugs are reported to have an immunomodulatory role, especially the gold salt, which influences the monocyte-macrophage system, it is suggested that the observed antiarthritic effects of disease-modifying antirheumatic drugs may be partly attributed to their immunomodulatory activity. PMID- 17848189 TI - Appropriate criteria for identification of near-miss maternal morbidity in tertiary care facilities: a cross sectional study. AB - BACKGROUND: The study of severe maternal morbidity survivors (near miss) may be an alternative or a complement to the study of maternal death events as a health care indicator. However, there is still controversy regarding the criteria for identification of near-miss maternal morbidity. This study aimed to characterize the near miss maternal morbidity according to different sets of criteria. METHODS: A descriptive study in a tertiary center including 2,929 women who delivered there between July 2003 and June 2004. Possible cases of near miss were daily screened by checking different sets of criteria proposed elsewhere. The main outcome measures were: rate of near miss and its primary determinant factors, criteria for its identification, total hospital stay, ICU stay, and number and kind of special procedures performed. RESULTS: There were two maternal deaths and 124 cases of near miss were identified, with 102 of them admitted to the ICU (80.9%). Among the 126 special procedures performed, the most frequent were central venous access, echocardiography and invasive mechanical ventilation. The mean hospital stay was 10.3 (+/- 13.24) days. Hospital stay and the number of special procedures performed were significantly higher when the organ dysfunction based criteria were applied. CONCLUSION: The adoption of a two level screening strategy may lead to the development of a consistent severe maternal morbidity surveillance system but further research is needed before worldwide near miss criteria can be assumed. PMID- 17848188 TI - Hypereosinophilic syndromes. AB - Hypereosinophilic syndromes (HES) constitute a rare and heterogeneous group of disorders, defined as persistent and marked blood eosinophilia (> 1.5 x 10(9)/L for more than six consecutive months) associated with evidence of eosinophil induced organ damage, where other causes of hypereosinophilia such as allergic, parasitic, and malignant disorders have been excluded. Prevalence is unknown. HES occur most frequently in young to middle-aged patients, but may concern any age group. Male predominance (4-9:1 ratio) has been reported in historic series but this is likely to reflect the quasi-exclusive male distribution of a sporadic hematopoietic stem cell mutation found in a recently characterized disease variant. Target-organ damage mediated by eosinophils is highly variable among patients, with involvement of skin, heart, lungs, and central and peripheral nervous systems in more than 50% of cases. Other frequently observed complications include hepato- and/or splenomegaly, eosinophilic gastroenteritis, and coagulation disorders. Recent advances in underlying pathogenesis have established that hypereosinophilia may be due either to primitive involvement of myeloid cells, essentially due to occurrence of an interstitial chromosomal deletion on 4q12 leading to creation of the FIP1L1-PDGFRA fusion gene (F/P+ variant), or to increased interleukin (IL)-5 production by a clonally expanded T cell population (lymphocytic variant), most frequently characterized by a CD3 CD4+ phenotype. Diagnosis of HES relies on observation of persistent and marked hypereosinophilia responsible for target-organ damage, and exclusion of underlying causes of hypereosinophilia, including allergic and parasitic disorders, solid and hematological malignancies, Churg-Strauss disease, and HTLV infection. Once these criteria are fulfilled, further testing for eventual pathogenic classification is warranted using appropriate cytogenetic and functional approaches. Therapeutic management should be adjusted to disease severity and eventual detection of pathogenic variants. For F/P+ patients, imatinib has undisputedly become first line therapy. For others, corticosteroids are generally administered initially, followed by agents such as hydroxycarbamide, interferon-alpha, and imatinib, for corticosteroid-resistant cases, as well as for corticosteroid-sparing purposes. Recent data suggest that mepolizumab, an anti-IL-5 antibody, is an effective corticosteroid-sparing agent for F/P-negative patients. Prognosis has improved significantly since definition of HES, and currently depends on development of irreversible heart failure, as well as eventual malignant transformation of myeloid or lymphoid cells. PMID- 17848190 TI - How to decide which are the most pertinent overly-represented features during gene set enrichment analysis. AB - BACKGROUND: The search for enriched features has become widely used to characterize a set of genes or proteins. A key aspect of this technique is its ability to identify correlations amongst heterogeneous data such as Gene Ontology annotations, gene expression data and genome location of genes. Despite the rapid growth of available data, very little has been proposed in terms of formalization and optimization. Additionally, current methods mainly ignore the structure of the data which causes results redundancy. For example, when searching for enrichment in GO terms, genes can be annotated with multiple GO terms and should be propagated to the more general terms in the Gene Ontology. Consequently, the gene sets often overlap partially or totally, and this causes the reported enriched GO terms to be both numerous and redundant, hence, overwhelming the researcher with non-pertinent information. This situation is not unique, it arises whenever some hierarchical clustering is performed (e.g. based on the gene expression profiles), the extreme case being when genes that are neighbors on the chromosomes are considered. RESULTS: We present a generic framework to efficiently identify the most pertinent over-represented features in a set of genes. We propose a formal representation of gene sets based on the theory of partially ordered sets (posets), and give a formal definition of target set pertinence. Algorithms and compact representations of target sets are provided for the generation and the evaluation of the pertinent target sets. The relevance of our method is illustrated through the search for enriched GO annotations in the proteins involved in a multiprotein complex. The results obtained demonstrate the gain in terms of pertinence (up to 64% redundancy removed), space requirements (up to 73% less storage) and efficiency (up to 98% less comparisons). CONCLUSION: The generic framework presented in this article provides a formal approach to adequately represent available data and efficiently search for pertinent over-represented features in a set of genes or proteins. The formalism and the pertinence definition can be directly used by most of the methods and tools currently available for feature enrichment analysis. PMID- 17848191 TI - Neuroimaging revolutionizes therapeutic approaches to chronic pain. AB - An understanding of how the brain changes in chronic pain or responds to pharmacological or other therapeutic interventions has been significantly changed as a result of developments in neuroimaging of the CNS. These developments have occurred in 3 domains : (1) Anatomical Imaging which has demonstrated changes in brain volume in chronic pain; (2) Functional Imaging (fMRI) that has demonstrated an altered state in the brain in chronic pain conditions including back pain, neuropathic pain, and complex regional pain syndromes. In addition the response of the brain to drugs has provided new insights into how these may modify normal and abnormal circuits (phMRI or pharmacological MRI); (3) Chemical Imaging (Magnetic Resonance Spectroscopy or MRS) has helped our understanding of measures of chemical changes in chronic pain. Taken together these three domains have already changed the way in which we think of pain - it should now be considered an altered brain state in which there may be altered functional connections or systems and a state that has components of degenerative aspects of the CNS. PMID- 17848192 TI - Staphylococcus aureus intestinal colonization is associated with increased frequency of S. aureus on skin of hospitalized patients. AB - BACKGROUND: Intestinal colonization by Staphylococcus aureus among hospitalized patients has been associated with increased risk of staphylococcal infection and could potentially contribute to transmission. We hypothesized that S. aureus intestinal colonization is associated with increased frequency of S. aureus on patients' skin and nearby environmental surfaces. METHODS: Selected inpatients were cultured weekly for S. aureus from stool, nares, skin (groin and axilla), and environmental surfaces (bed rail and bedside table). Investigator's hands were cultured after contacting the patients' skin and the environmental surfaces. RESULTS: Of 71 subjects, 32 (45.1%) had negative nares and stool cultures, 23 (32.4%) had positive nares and stool cultures, 13 (18.3%) were nares carriers only, and 3 (4.2%) were stool carriers only. Of the 39 patients with S. aureus carriage, 30 (76.9%) had methicillin-resistant isolates. In comparison to nares colonization only, nares and intestinal colonization was associated with increased frequency of positive skin cultures (41% versus 77%; p = 0.001) and trends toward increased environmental contamination (45% versus 62%; p = 0.188) and acquisition on investigator's hands (36% versus 60%; p = 0.057). Patients with negative nares and stool cultures had low frequency of S. aureus on skin and the environment (4.8% and 11.3%, respectively). CONCLUSION: We found that hospitalized patients with S. aureus nares and/or stool carriage frequently had S. aureus on their skin and on nearby environmental surfaces. S. aureus intestinal colonization was associated with increased frequency of positive skin cultures, which could potentially facilitate staphylococcal infections and nosocomial transmission. PMID- 17848193 TI - TGFB1 and TGFBR1 polymorphisms and breast cancer risk in the Nurses' Health Study. AB - BACKGROUND: Transforming growth factor beta 1 (TGFB1) forms a signaling complex with transforming growth factor beta receptors 1 and 2 and has been described as both a tumor suppressor and tumor promoter. Single nucleotide polymorphisms in TGFB1 and a microsatellite in TGFBR1 have been investigated for association with risk of breast cancer, with conflicting results. METHODS: We examined polymorphisms in the promoter region of the TGFB1 gene as well as the TGFBR1*6A microsatellite in the Nurses' Health Study cohort. RESULTS: No overall associations between the L10P polymorphism of TGFB1 or the TGFBR1 microsatellite were detected. However, we observed an inverse association between the -509 C/T polymorphism of TGFB1 (p-trend = 0.04), which was stronger and more significant among women with estrogen receptor positive breast cancer. CONCLUSION: Polymorphisms in the promoter region of TGFB1 are not likely to be associated with large increases in breast cancer risk overall among Caucasian women. PMID- 17848195 TI - Decision making: rational or hedonic? AB - Three experiments studied the hedonicity of decision making. Participants rated their pleasure/displeasure while reading item-sentences describing political and social problems followed by different decisions (Questionnaire 1). Questionnaire 2 was multiple-choice, grouping the items from Questionnaire 1. In Experiment 1, participants answered Questionnaire 2 rapidly or slowly. Both groups selected what they had rated as pleasant, but the 'leisurely' group maximized pleasure less. In Experiment 2, participants selected the most rational responses. The selected behaviors were pleasant but less than spontaneous behaviors. In Experiment 3, Questionnaire 2 was presented once with items grouped by theme, and once with items shuffled. Participants maximized the pleasure of their decisions, but the items selected on Questionnaires 2 were different when presented in different order. All groups maximized pleasure equally in their decisions.These results support that decisions are made predominantly in the hedonic dimension of consciousness. PMID- 17848194 TI - Factors considered by medical students when formulating their specialty preferences in Japan: findings from a qualitative study. AB - BACKGROUND: Little research addresses how medical students develop their choice of specialty training in Japan. The purpose of this research was to elucidate factors considered by Japanese medical students when formulating their specialty choice. METHODS: We conducted qualitative interviews with 25 Japanese medical students regarding factors influencing specialty preference and their views on roles of primary versus specialty care. We qualitatively analyzed the data to identify factors students consider when developing specialty preferences, to understand their views about primary and subspecialty care, and to construct models depicting the pathways to specialization. RESULTS: Students mention factors such as illness in self or close others, respect for family member in the profession, preclinical experiences in the curriculum such as labs and dissection, and aspects of patient care such as the clinical atmosphere, charismatic role models, and doctor-patient communication as influential on their specialty preferences. Participating students could generally distinguish between subspecialty care and primary care, but not primary care and family medicine. Our analysis yields a "Two Career" model depicting how medical graduates can first train for hospital-based specialty practice, and then switch to mixed primary/specialty care outpatient practice years later without any requirement for systematic training in principles of primary care practice. CONCLUSION: Preclinical and clinical experiences as well as role models are reported by Japanese students as influential factors when formulating their specialty preferences. Student understanding of family medicine as a discipline is low in Japan. Students with ultimate aspirations to practice outpatient primary care medicine do not need to commit to systematic primary care training after graduation. The Two Career model of specialization leaves the door open for medical graduates to enter primary care practice at anytime regardless of post graduate residency training choice. PMID- 17848196 TI - Insights into spatial configuration of a galactosylated epitope required to trigger arthritogenic T-cell receptors specific for the sugar moiety. AB - The immunodominant epitope of bovine type II collagen (CII256-270) in Aq mice carries a hydroxylysine-264 linked galactose (Gal-Hyl264), the recognition of which is central to the development of collagen-induced arthritis. This study explores the molecular interactions involved in the engagement of T-cell receptors (TCRs) with such epitopes. Responses of three anti-CII T-cell hybridomas and clone A9.2 (all sharing close TCR sequences) to a panel of CII256 270 analogues incorporating Gal-Hyl264 with a modified side chain were determined. Recognition of naturally occurring CII256-270 peptides by either group of T cells depended strictly upon the presence of the carbohydrate and, more precisely, its intact HO-4 group. Modifications of primary amino group on the hydroxylysine side chain eliminated T-cell reactivity, notwithstanding the presence of the galactosyl moiety. Moderate stereochemical changes, such as altered sugar orientation and methylation at the galactose anchor position, were still permissive. Conversely, robust transformations affecting the relative positions of the key elements were detrimental to TCR recognition. To conclude, these data provide strong new experimental evidence that integrity of both galactose HO-4 and hydroxylysine side chain primary amino groups are mandatory for activation of anti-Gal-Hyl264 TCRs. They also indicate that there is a certain degree of TCR plasticity in peptide-TCR interactions. PMID- 17848197 TI - Bilateral synchronous breast carcinomas followed by a metastasis to the gallbladder: a case report. AB - BACKGROUND: Breast cancer is usually associated with metastases to lungs, bones and liver. Breast carcinoma metastasizing to the gallbladder is very rare. CASE PRESENTATION: A 59-year-old woman presented with bilateral synchronous breast lesions. A palpable, retroareolar solid lesion of diameter equal to 5 cm was present in the right breast, and a newly developed, non-palpable lesion with microcalcifications (diameter equal to 0.7 cm) was present in the upper outer quadrant of the left breast. Modified radical mastectomy was performed on the right breast and lumpectomy after hook-wire localization was performed on the left breast, combined with lymph node dissection in both sides. The pathological examination revealed invasive lobular carcinoma grade II in the right breast and invasive ductal carcinoma grade I in the left breast. Chemotherapy, radiation therapy, trastuzumab and letrozole were appropriately administered. At her 18 month follow-up, the patient was free of symptoms; the imaging tests (chest CT, abdominal U/S, bone scan), biochemical tests, blood cell count and tumor markers were also normal. At the 20th month after surgery however, the patient developed symptoms of cholecystitis and underwent cholecystectomy. The histopathological examination revealed metastasis of the lobular carcinoma to the gallbladder. CONCLUSION: This extremely rare case confirms on a single patient the results of large series having demonstrated the preferential metastasis of lobular breast cancer to the gallbladder. Symptoms of cholecystitis should not be neglected in such patients, as they might indicate metastasis to the gallbladder. PMID- 17848198 TI - Environmental Health: the first five years. PMID- 17848199 TI - Becoming the best mom that I can: women's experiences of managing depression during pregnancy--a qualitative study. AB - BACKGROUND: The purpose of this constructivist grounded theory study was to develop a theoretical model that explains women's processes of managing diagnosed depression when pregnant. METHODS: We explored the experiences of 19 women in Ontario who were diagnosed with depression during their pregnancy. RESULTS: The model that emerged from the analysis was becoming the best mom that I can. Becoming the best mom that I can explains the complex process of the women's journey as they travel from the depths of despair, where the depression is perceived to threaten their pregnancy and their ability to care for the coming baby, to arrive at knowing the self and being in a better place. In order to reground the self and regain control of their lives, the women had to recognize the problem, overcome shame and embarrassment, identify an understanding healthcare provider, and consider the consequences of the depression and its management. When confronting and confining the threat of depression, the women employed strategies of overcoming barriers, gaining knowledge, and taking control. As a result of counseling, medication, or a combination of both, women felt that they had arrived at a better place. CONCLUSION: For many women, the idea that depression could occur during pregnancy was antithetical to their vision of the pregnant self. The challenge for a pregnant woman who is diagnosed with depression, is that effective care for her may jeopardize her baby's future health. This provides a dilemma for about-to-be parents and their healthcare providers. Improved awareness of depression during pregnancy on the part of healthcare professionals is needed to improve the women's understanding of this disorder and their ability to recognize and seek help with depression should it occur during the prenatal period. Further qualitative research is needed to determine the specific aspects that need to be addressed in such classes. PMID- 17848200 TI - Glaucoma following congenital cataract surgery--the role of early surgery and posterior capsulotomy. AB - BACKGROUND: To determine the rate of glaucoma following congenital cataract surgery at Moorfields Eye Hospital (MEH), and to investigate potential risk factors for glaucoma in our case series. METHODS: A retrospective case notes review was undertaken of all congenital cataract lensectomies performed at MEH between 1994 and 2000. The following parameters were ascertained: age at surgery, unilateral or bilateral cataract, whether a posterior capsulotomy (PC) was performed at the time of surgery, whether an intraocular lens (IOL) was inserted, duration of follow-up, and if aphakic glaucoma (AG) developed. All lensectomies were performed through a limbal incision by a single consultant surgeon. RESULTS: A total of 47 subjects were identified - 40 patients with bilateral cataracts and 7 with unilateral. Of the 40 bilateral cataract patients, 76 eyes had lensectomies; with 37 of these patients (71 lensectomies) having at least 5 year follow-up. Based on patient count, the 5 year risk of AG in at least one eye following surgery was 21.6%. Based on eye count, the 5 year risk of AG after lensectomy was 15.5%. The average age at surgery of patients who did not develop AG, and had at least 5 years follow-up, was 28.7 months (range 2 weeks to 6 years), with 20% having surgery within the first month of life. In comparison, the average age at surgery of patients with at least 5 years follow-up, who developed AG was 1.6 months (range 2 weeks to 7 months), with 60% having surgery within the first month of life. In subjects with at least 5 years follow-up, a PC rate of 100% was identified in the eyes that developed AG, compared to 61% in eyes that did not develop AG. An IOL was inserted in O% of eyes with AG, compared to 57% in eyes that did not develop AG. Onset of AG ranged from one month post surgery to 7 years, with an average yearly incidence of 5.3%. CONCLUSION: Early surgery in patients with bilateral cataracts is associated with a marked increase in risk of AG. Our data suggest that an intact posterior capsule may be associated with a lower rate of AG. PMID- 17848201 TI - Occlusal management for a patient with aural symptoms of unknown etiology: a case report. AB - BACKGROUND: Although the discrepancy between the habitual occlusal position (HOP) and the flat bite plate-induced occlusal position (BPOP) (regarded as the muscular physiological reference position) has been recently reported to be related to symptoms of temporomandibular disorders (TMDs), it still remains unclear whether the occlusal equilibration in the reference position is effective to resolve TMD-related discrepancy and symptoms. Aural symptoms (otalgia, tinnitus, vertigo et cetera) have been included under TMD symptoms. METHODS: To examine the effect of occlusal equilibration for the treatment of TMDs, occlusal equilibration was performed for a patient with aural symptoms (otalgia, tinnitus and vertigo) of unknown etiology in the right ear. An occlusal analysis was performed on this patient with dental models mounted on an articulator after relieving painful symptoms by an appliance therapy and a discrepancy was identified (p < 0.005). Occlusal equilibration in the BPOP was then performed for the patient by selective tooth grinding, because it was estimated that the interocclusal space between upper and lower occlusal surfaces would be rectified by selective grinding. RESULTS: At completion of treatment, the discrepancy was not significant (p > 0.25), and the patient's right condyle had shifted 2.8 mm posteromedially in the horizontal plane, and the left condyle had shifted 1.0 mm laterally in the voluntarily closed position from the previous HOP. The aural symptoms of the patient were resolved, and there has been no recurrence to date after a two-year follow-up period. CONCLUSION: An occlusal analysis should be performed in patients exhibiting TMD symptoms to identify the presence or absence of any discrepancy between the HOP and the BPOP. If a discrepancy exists, occlusal equilibration should be attempted in the reference position. PMID- 17848202 TI - Solution structure of the second bromodomain of Brd2 and its specific interaction with acetylated histone tails. AB - BACKGROUND: Brd2 is a transcriptional regulator and belongs to BET family, a less characterized novel class of bromodomain-containing proteins. Brd2 contains two tandem bromodomains (BD1 and BD2, 46% sequence identity) in the N-terminus and a conserved motif named ET (extra C-terminal) domain at the C-terminus that is also present in some other bromodomain proteins. The two bromodomains have been shown to bind the acetylated histone H4 and to be responsible for mitotic retention on chromosomes, which is probably a distinctive feature of BET family proteins. Although the crystal structure of Brd2 BD1 is reported, no structure features have been characterized for Brd2 BD2 and its interaction with acetylated histones. RESULTS: Here we report the solution structure of human Brd2 BD2 determined by NMR. Although the overall fold resembles the bromodomains from other proteins, significant differences can be found in loop regions, especially in the ZA loop in which a two amino acids insertion is involved in an uncommon pi helix, termed piD. The helix piD forms a portion of the acetyl-lysine binding site, which could be a structural characteristic of Brd2 BD2 and other BET bromodomains. Unlike Brd2 BD1, BD2 is monomeric in solution. With NMR perturbation studies, we have mapped the H4-AcK12 peptide binding interface on Brd2 BD2 and shown that the binding was with low affinity (2.9 mM) and in fast exchange. Using NMR and mutational analysis, we identified several residues important for the Brd2 BD2-H4-AcK12 peptide interaction and probed the potential mechanism for the specific recognition of acetylated histone codes by Brd2 BD2. CONCLUSION: Brd2 BD2 is monomeric in solution and dynamically interacts with H4 AcK12. The additional secondary elements in the long ZA loop may be a common characteristic of BET bromodomains. Surrounding the ligand-binding cavity, five aspartate residues form a negatively charged collar that serves as a secondary binding site for H4-AcK12. We suggest that Brd2 BD1 and BD2 may possess distinctive roles and cooperate to regulate Brd2 functions. The structure basis of Brd2 BD2 will help to further characterize the functions of Brd2 and its BET members. PMID- 17848204 TI - How expensive is antipsychotic polypharmacy? Experience from five US state Medicaid programs. AB - OBJECTIVE: To characterize healthcare costs associated with antipsychotic polypharmacy and to investigate predictors of high-cost patients. METHODS: A retrospective cohort study using Medicaid claims data from California, Nebraska, Oregon, Utah, and Wyoming evaluated 55 383 fee-for-service patients with antipsychotic prescriptions between 1998 and 2002. Polypharmacy was defined as initiating multiple antipsychotic drugs or concomitant antipsychotic therapy (>or=60 days). Healthcare costs (drug and non-drug) were summed for 365 days following index antipsychotic claim. Adjusted mean costs were compared to antipsychotic monotherapy. Logistic regression was performed to identify predictors of high-cost patients (top quintile) with regard to patient age, gender, race/ethnicity, mental disorders, hospitalization, index antipsychotic, concomitant psychotropic drugs, and polypharmacy. RESULTS: The average annual prevalence of antipsychotic polypharmacy was 6%. 70-80% of total healthcare expenditures for polypharmacy patients were drug-related. Polypharmacy was associated with significantly higher drug expenditures ($1716-2079) in the year following drug initiation than monotherapy even after adjusting for case mix and index antipsychotic (p < 0.05). Differences in non-drug expenditures versus monotherapy were smaller and varied by state ranging from a $77 increase in California (p < 0.001) to a $211 savings in Utah (p = 0.02). In California, polypharmacy alone (OR = 2.69; 95% CI: 2.30-3.16) or in combination with concomitant psychotropics (OR = 6.26; 95% CI: 5.51-7.11) was associated with greater likelihood of being a high-cost patient than monotherapy. CONCLUSIONS: Cost savings from limiting antipsychotic polypharmacy could be significant. Caution must be taken in ensuring reductions in polypharmacy do not lead to unintended consequences or shift care to more costly alternatives. Study limitations, including the known shortcomings of claims data and differences across state Medicaid programs, should be considered when interpreting the results of this or any multi-state study. PMID- 17848203 TI - The embryonic muscle transcriptome of Caenorhabditis elegans. AB - BACKGROUND: The force generating mechanism of muscle is evolutionarily ancient; the fundamental structural and functional components of the sarcomere are common to motile animals throughout phylogeny. Recent evidence suggests that the transcription factors that regulate muscle development are also conserved. Thus, a comprehensive description of muscle gene expression in a simple model organism should define a basic muscle transcriptome that is also found in animals with more complex body plans. To this end, we applied microarray profiling of Caenorhabtidis elegans cells (MAPCeL) to muscle cell populations extracted from developing C. elegans embryos. RESULTS: We used fluorescence-activated cell sorting to isolate myo-3::green fluorescent protein (GFP) positive muscle cells, and their cultured derivatives, from dissociated early C. elegans embryos. Microarray analysis identified 7,070 expressed genes, 1,312 of which are enriched in the myo-3::GFP positive cell population relative to the average embryonic cell. The muscle enriched gene set was validated by comparisons with known muscle markers, independently derived expression data, and GFP reporters in transgenic strains. These results confirm the utility of MAPCeL for cell type specific expression profiling and reveal that 60% of these transcripts have human homologs. CONCLUSION: This study provides a comprehensive description of gene expression in developing C. elegans embryonic muscle cells. The finding that more than half of these muscle enriched transcripts encode proteins with human homologs suggests that mutant analysis of these genes in C. elegans could reveal evolutionarily conserved models of muscle gene function, with ready application to human muscle pathologies. PMID- 17848206 TI - Decreased levels of interleukin-10 and transforming growth factor-beta 2 in cerebrospinal fluid of patients with high grade astrocytoma. AB - OBJECTIVE: Glioma cells can produce anti-inflammatory cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) which inhibit T cell and monocyte function. It is unknown if production of these cytokines is limited to the site of tumor or these molecules are also released to cerebrospinal fluid and blood. The goal of our study was to determine if patients with astrocytoma have increased levels of IL-10 and TGF-beta 2 in cerebrospinal fluid (CSF) and serum. METHODS: CSF and serum samples were taken from 16 patients with astrocytoma of grade III or grade IV according to the WHO classification and from 28 age- and gender-matched controls (patients with normal pressure hydrocephalus or with lumbar disk herniation). Cytokine concentrations were measured using ELISA methods. RESULTS AND DISCUSSION: There was no difference in serum levels of IL-10 and TGF-beta 2 between groups. Patients with astrocytoma had decreased levels of IL-10 (0.9 +/- 1.2 versus 3.5 +/- 9.2 pg/ml, p=0.01) and TGF-beta 2 (0.0 +/- 0.0 versus 5.4 +/- 9.4 pg/ml, p=0.05) in CSF compared to controls. Because serum IL-10 and TGF-beta 2 levels are similar in patients with astrocytoma and in controls, these cytokines are probably not directly involved in peripheral monocyte and T cell deactivation. PMID- 17848207 TI - Source analysis of the magnetic field evoked during self-paced finger movements. AB - OBJECTIVE: The aim of this study is to investigate a source of cortical magnetic fields evoked by index finger movements. METHODS: We analysed both movement related cortical fields (MRCFs) and somatosensory-evoked fields (SEFs) by single equivalent current dipole (ECD) method in six healthy subjects. Dipole locations were superimposed on MR images of each individual subject. RESULTS: The first component after finger movement (movement-evoked field I, MEFI) was observed in all subjects. The dipole of MEFI was oriented posteriorly, and was located on the posterior wall of the central sulcus of the hemisphere contralateral to the movement. The SEFs showed three major components: N20m, P30m and P60m. The dipoles of P30m and P60m were orientated posteriorly, similarly to the MEFI dipole, while that of N20m was orientated anteriorly. The dipole location of MEFI was closely located to P60m, not to N20m and P30m. The mean location of the MEFI dipole was significantly (p<0.05) superior to N20m. CONCLUSION: These findings suggest that MEFI would be generated in the sensory area (area 3b) affected by multiple afferents and activities, and that the source of the MEFI is not identical to that of the N20m component. PMID- 17848208 TI - Sensory (nociceptive) stimulation evokes Fos expression in the subthalamus of hemiparkinsonian rats. AB - OBJECTIVE: In an effort to understand cell activity patterns and sensorimotor integration in Parkinson's disease, we have explored the expression of the Fos protein in the subthalamus after sensory (nociceptive) stimulation of hemiparkinsonian Sprague-Dawley rats [6-hydroxydopamine [6OHDA]-lesioned]. Fos is a marker for neuronal activity in most areas of the brain and the subthalamus is a major driving force of the basal ganglia and target for surgical intervention in parkinsonian patients. METHODS: The medial forebrain bundle (major tract carrying dopaminergic nigrostriatal axons) was injected with either 6OHDA or saline (controls). A week later, some rats were subjected to mechanical stimulation (pinching; activating nociceptive pathways) of the hindpaw for 2 hours, while others received no stimulation. Thereafter, brains were processed using routine tyrosine hydroxylase (TH; marker for dopaminergic cells) or Fos immunocytochemistry. RESULTS: In the cases that had saline injections combined with mechanical stimulation or with no stimulation, as well as those that had 6OHDA lesions combined with no stimulation, there were no Fos+ cells in the subthalamus. However, in the cases that had 6OHDA-lesions combined with mechanical stimulation, there were many Fos+ cells within the subthalamus of both sides, particularly on the ipsilateral side. DISCUSSION: Our results indicate that after an increase in sensory (nociceptive) activity, via mechanical stimulation, there is an induction of Fos expression in the subthalamus of 6OHDA lesioned cases. We suggest that activating nociceptive pathways exacerbates the abnormal cell activity in the basal ganglia generated by the hemiparkinsonian condition. PMID- 17848209 TI - Metabolite concentration ratios in thalami of patients with migraine and trigeminal neuralgia measured with 1H-MRS. AB - OBJECTIVE: To investigate the metabolite concentration ratios including N acetylaspartate (NAA), choline-containing compounds (Cho) and creatine plus phosphocreatine (Cr) in thalami of patients with migraine without aura, patients with trigeminal neuralgia and healthy comparison subjects using multi-voxel proton magnetic resonance spectroscopy (1H-MRS). METHODS: 1H-MRS was performed with a 3.0 T MR system on the thalamus bilaterally in 20 patients with migraine without aura, 16 patients with trigeminal neuralgia and 14 healthy control subjects. RESULTS: In the patients with trigeminal neuralgia, metabolite concentration ratios except for Cho/Cr in thalami were different from those of healthy subjects (p>0.05). In migraine group, only NAA/Cho is low in the left thalamus (p>0.05). Comparing the metabolite concentration ratios of affected and contralateral sides in migraine and trigeminal neuralgia groups, only NAA/Cr showed a significant difference (p>0.05). CONCLUSION: It was proved that migraine and trigeminal neuralgia seemed to be associated with an abnormal balance of the neural activity in the thalamus using 1H-MRS. There was some significant difference between metabolite concentration ratios in two diseases. 1H-MRS may serve as a useful non-invasive tool for evaluating thalamic neural activity and therapy effect in clinical performance of patients with migraine without aura. PMID- 17848210 TI - Dental X-rays accurately predict osteoporosis risk. PMID- 17848211 TI - Special diet may help smokers quit. PMID- 17848212 TI - Herpetic retinitis. AB - This paper provides an appreciation of the various forms and consequences of retinal inflammation caused by human herpesviruses. Herpes simplex virus types 1 and 2, varicella zoster virus, cytomegalovirus and Epstein-Barr virus are known to cause retinitis. The prognosis of herpetic retinitis remains poor because it is associated with a high incidence of complications, both during and after the acute disease phase. On diagnosis of retinal necrosis, antiviral treatment must be started promptly to limit disease progression; following this, prophylactic maintenance therapy may be required. PMID- 17848213 TI - Management of HSV encephalitis in adults and neonates: diagnosis, prognosis and treatment. AB - Herpes simplex virus (HSV) infections of the central nervous system (CNS) are infrequent in occurrence, but potentially devastating in outcome. Tremendous advances in the ability to diagnose HSV CNS disease without the need for invasive procedures such as brain biopsy, coupled with the establishment of safe and effective antiviral therapies, have improved overall outcomes. However, the seriousness of HSV CNS infections requires that clinicians maintain a high index of suspicion to initiate evaluation under suitable circumstances. In addition, clinicians need an understanding of the clinical disease course in order to interpret the diagnostic tests appropriately. Intravenous aciclovir remains the mainstay of antiviral management. Even with recent treatment advances and enhanced awareness, potentially devastating outcomes remain possible. PMID- 17848214 TI - Viral load in congenital cytomegalovirus infection. AB - Cytomegalovirus (CMV) affects 50-80% of adults in the USA by the age of 40 and is the virus most commonly transmitted to the fetus before birth. Extensive research into quantitative CMV assays, and the proven value of CMV DNA load measurement in guiding antiviral therapy in haematopoietic stem cell and solid organ transplant recipients, has paved the way for evaluating viral load (VL) in the management of congenital CMV infection. This article discusses the rapidly evolving methods of VL measurement. It is hoped that VL may be used in the future to predict outcome and assist antiviral treatment plans. Having the ability to detect CMV-infected infants at risk of developing hearing loss and/or disseminated CMV disease may allow the selection of patients who are most likely to benefit from timely initiation of antiviral therapy. PMID- 17848215 TI - Review of recent HSV recurrent-infection treatment studies. AB - Antiviral management options for recurrent herpes simplex virus (HSV) infection include daily suppressive and episodic therapy. New data on patient-initiated, short-course, high-dose antiviral therapy provide a new, more convenient option for patients who choose episodic therapy. A head-to-head comparison of suppressive valaciclovir versus famciclovir treatment indicates that both drugs have comparable clinical benefits, but that valaciclovir may have a greater impact on virological end-points. However, a more recent study shows that famciclovir effectively reduces the frequency of total and subclinical HSV shedding compared with placebo, as well as the percentage of days with genital lesions for subjects with or without a history of genital herpes. This article reports on presentations given at the IHMF Annual Meeting and International Congress of Antimicrobial Agents and Chemotherapy, both of which took place in late 2006. PMID- 17848226 TI - Conservative management of bilateral Sertoli cell tumors of the testicle in association with the Carney complex: a case report. AB - Large cell calcifying Sertoli cell tumor of the testicle is a rare, hormonally active sex cord-stromal tumor seen in patients with Carney complex. When such tumors occur bilaterally, treatment options for preserving fertility and addressing the secondary effects of excess hormone production must be considered. The availability of specific antiestrogen drugs means that bilateral orchiectomy for this benign tumor may no longer be warranted. Testicular-sparing surgery and advances in reproductive technology may also improve the overall prognosis for fertility. Gynecomastia in prepubescent boys can be emotionally very distressing. Approximately two thirds of teenaged boys will develop some degree of breast enlargement that spontaneously regresses as testosterone levels rise (Ill Med J 1938;73:113). In all cases, a thorough history and physical examination are required to exclude nonphysiologic causes such as drugs, pulmonary disease, chronic liver disease, exogenous estrogens, and estrogen-producing tumors (Seashore J. Disorders of the breast. In: Rowe MI, O'Neill JA, Grosfeld JL et al, editors. Pediatric surgery, 5th ed. St Louis (MO): Mosby Year Book, 1998). We report on a child who presented with a 2-year history of gynecomastia with associated bilateral testicular swellings and discuss a novel treatment strategy for managing bilateral testicular tumors in the context of the Carney complex. PMID- 17848225 TI - Feingold syndome: a rare but important cause of syndromic tracheoesophageal fistula. AB - Esophageal atresia (EA) and tracheoesophageal fistula (TEF) are common congenital malformations and are associated with additional anomalies in approximately half of cases. Feingold syndrome is an important genetic cause of syndromic EA-TEF to consider in patients with associated microcephaly and digital anomalies. We present a case report of a male infant with EA-TEF, microcephaly, subtle facial dysmorphism, dysplastic kidney, short fifth fingers, second finger clinodactyly, and increased spacing between the first and second toes bilaterally. His clinical presentation was suggestive of Feingold syndrome, and genetic testing of the MYCN gene confirmed the diagnosis. Feingold syndrome is an autosomal dominant condition, and therefore, the diagnosis has important implications for genetic counseling. PMID- 17848227 TI - Hyperthermic intraperitoneal chemoperfusion is an option for treatment of peritoneal carcinomatosis in children. AB - BACKGROUND: Gastrointestinal carcinomas in childhood are rare and frequently present at an advanced stage. Besides lymphatic and distant organ metastasis, peritoneal carcinomatosis may be detected and has a poor prognosis. In addition to surgery and intravenous chemotherapy, hyperthermic intraperitoneal chemoperfusion (HIPEC) may be an option for selected patients. Our aim was to demonstrate the feasibility of the method and to discuss possible indications. METHODS: After treating a series of adult patients, HIPEC for peritoneal carcinomatosis from a signet cell carcinoma of the colon was performed intraoperatively in a 12-year-old boy. We gave mitomycin C at a dose of 30 mg/m2 over 90 minutes at maximum temperature of 41.2 degrees C. We performed intraoperative drug level monitoring and daily postoperative liver and kidney function tests and differential blood counts. RESULTS: Hyperthermic intraperitoneal chemoperfusion was performed according to protocol without complications. Perfusate and venous drug levels were similar to those in an adult case. The patient had an uneventful recovery, and serum chemistry and blood count returned to normal after a week. The boy lived for 36 months after initial presentation. Sixteen months after HIPEC, still with excellent quality of life, an elevated carcinoembryonic antigen (CEA) indicated recurrence. Thirty months after HIPEC, he died of progressive recurrent disease. CONCLUSIONS: Hyperthermic intraperitoneal chemoperfusion as performed in adults may be beneficial to children with peritoneal carcinomatosis and merits further study. PMID- 17848228 TI - Anorectal impalement in a pediatric patient with transanal evisceration of small bowel. AB - Rectal injuries in the pediatric population are most often attributed to accidental falls on offending objects, sexual abuse, or blunt trauma. Anorectal impalement is a rare injury, and as a result, specific knowledge or experience on the treatment of this type of injury in children is sparse. The extent of injury is often difficult to assess. Mostly, therapeutical decisions are based on general knowledge in adults. We present a case of accidental anorectal impalement in a child by a fall on the handle of a toilet brush. The handle caused an anterior rupture of the intraperitoneal part of the rectum with subsequent transanal evisceration of several loops of small bowel. PMID- 17848229 TI - Congenital true pancreatic cyst detected prenatally in neonate: a case report. AB - True congenital epithelium-lined cysts of the pancreas are rare, and the prenatal diagnosis of a true pancreatic cyst has been reported only rarely. In this article, the authors report a 3-day-old girl with histologically proven true pancreatic cyst that was detected by prenatal ultrasonography. The cystic mass was located in the left upper side of the abdomen, and total cystectomy was performed without complication. PMID- 17848230 TI - Anorectal hamartoma in a neonate: a unique anorectal mass. AB - Neonates presenting with perineal masses are uncommon. When encountered, most perineal masses are anorectal malformations, sacrococcygeal teratomas, rectal prolapse, or duplication cysts. We present an otherwise healthy newborn with a patent anal canal and a pedunculated anal mass. The mass was initially believed to be a prolapsed rectal duplication cyst. Further evaluation for concomitant congenital abnormalities was negative. The patient underwent mass excision at the bedside under local anesthesia. Histopathologic evaluation revealed benign hamartoma. This case is presented because of its rarity, unique presentation, and simplicity of management. PMID- 17848231 TI - Videosialoendoscopic assessment of bilateral atresia of the Wharton's duct orifice in an infant. AB - Atresia of the submandibular ducts (particularly the duct orifice) is a rare occurrence that is mainly observed in newborns or infants; moreover, its differential diagnosis with other anomalies of the oral floor is sometimes difficult. Given the lack of data concerning the differences between atresia of the orifice of Wharton's duct and other anomalies of the submandibular duct system, we describe here the findings of videosialoendoscopic assessment of the salivary duct system in an infant who underwent traditional surgery for bilateral atresia of the orifice of Wharton's duct. During sialoendoscopy, a trifurcation of the main duct, a normal variant of the more common bifurcation of the secondary branches of the salivary duct system, was observed bilaterally. No other ductal anomalies were encountered. Complete resolution of the symptoms and complete patency of both ducts at 19-month follow-up evaluation were observed. In conclusion, although spontaneous resolution of the disease during feeding is possible, minimal incision of the orifice of the imperforated submandibular duct together with diagnostic videosialoendoscopy of the main salivary duct system may be considered as part of the modern approach to salivary obstructive disorders in pediatric age as is currently the case for sialolithiasis and recurrent juvenile parotitis. PMID- 17848232 TI - Topical application of mitomycin C in the treatment of esophageal and tracheobronchial stricture: a report of 2 cases. AB - We present 2 cases of successful treatment of recurrent anastomotic strictures using a topical application of mitomycin C. In the first case, a 4-year-old boy had a cervical cyst excised, which appeared to be an ectopic gastric mucosa. He consequently presented severe stenosis at the origin of the cervical esophagus that needed repeated balloon dilatations. The second case is about a 12-year-old girl who presented a traumatic complete rupture of the right mainstem bronchus managed by primary repair, with subsequent anastomotic stricture. Both patients were successfully managed with topical application of mitomycin C (1 mg/mL), and needed no more dilatations. PMID- 17848233 TI - Esophageal replacement in the neonatal period in infants with esophageal atresia and tracheoesophageal fistula. AB - AIM: The aim of the study was to assess the outcome after esophageal replacement using gastric pull-up performed in critically ill neonates with esophageal atresia (EA) and tracheoesophageal fistula. METHODS: During 1998 to 2005, gastric transposition was performed in 27 neonates (mean birth weight, 2.32 kg [1.86-3.0 kg]; mean age, 6.08 days) for post-EA and tracheoesophageal fistula leaks in 17, long gap in 6, and pure EA in 4, using transhiatal route in all. Pyloromyotomy as the drainage procedure was added for all 27 neonates. Patients were followed up at 3, 6, and 12 months for clinical evaluation, gastric clearance, duodenogastric reflux, and gastric pressure profile. RESULTS: Six neonates had ongoing serious chest infection, 3 had lung collapse, and 2 had associated congenital heart disease. Postoperative elective ventilation was provided to all neonates for 2 to 40 days (mean, 10.6 days). Nine neonates developed postoperative leaks in the neck; all healed spontaneously before discharge. Mean hospital stay was 32.6 days (range, 9-87 days). Four newborns died on postoperative days 9, 13, 15, and 29 because of existing severe sepsis in 3 and major congenital heart disease in 1. Functional evaluations were done at 3, 6, and 12 months postoperatively. Values at 6 months revealed normal gastric emptying in 16 of 23, presence of duodenal gastric reflux in 11 of 23, and mass contractions with significant rise in intragastric pressure after bolus feeds in 16 of 23 cases. Values at 12 months revealed normal gastric emptying in 14 of 20, presence of duodenal gastric reflux in 8 of 20, and mass contractions with significant rise in intragastric pressure after bolus feeds in 13 (65%) of 20 cases. CONCLUSION: Gastric transposition could be a lifesaving alternative to diversion, even in the critically ill newborns after major leaks. However, it requires technical surgical expertise and an effective pain relief and neonatal intensive care. PMID- 17848234 TI - Risk factors for recurrent gastroesophageal reflux disease after fundoplication in pediatric patients: a case-control study. AB - BACKGROUND/PURPOSE: Recurrent gastroesophageal reflux disease (rGERD) is a common problem after fundoplication. Previous studies attempting to identify risk factors for rGERD have failed to control for confounding variables. The purpose of this study was to identify significant risk factors for rGERD after controlling for potential confounding variables. METHODS: A retrospective, matched case-control study was conducted at a tertiary children's hospital. Cases (n = 116) met 1 of these criteria: reoperation for rGERD, symptomatic rGERD (confirmed by upper gastrointestinal series, esophagogastroduodenoscopy, or pH monitoring), or postoperative reinstitution of antireflux medication for more than 8 weeks. Controls (n = 209) were matched for surgeon, approach (laparoscopic/open), technique (partial/complete), and approximate operative date. Univariate and multivariable associations were analyzed by conditional logistic regression. RESULTS: Significant risk factors for rGERD were age of less than 6 years (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.7-7.5), preoperative hiatal hernia (OR, 3.2; 95% CI, 1.4-7.3), postoperative retching (OR, 5.1; 95% CI, 2.6-10.0), and postoperative esophageal dilatation (OR, 10.8; 95% CI, 1.8-65.4). Interestingly, significant association was not found between neurologic impairment and rGERD after controlling for potential confounding variables. CONCLUSION: Age of less than 6 years, preoperative hiatal hernia, postoperative retching, and postoperative esophageal dilatation are independently associated with increased risk of rGERD. Neurologic impairment alone does not increase the risk of developing rGERD. PMID- 17848235 TI - Gastroesophageal reflux and behavior in neurologically impaired children. AB - OBJECTIVE: This study aimed to evaluate a possible link between gastroesophageal reflux (GER) and behavior pattern indicating pain experience in a group of children with severe neurologic deficits. PATIENTS AND METHODS: We prospectively evaluated 19 patients with severe neurologic impairment (10 males and 9 females; mean age, 12.7 years) suspected for GER before and after initial treatment. Repeated 24-hour pH monitorings were performed in 19 children, whereas additional repeated endoscopic investigations were carried out in 18. In these children a histologic examination of mucosal biopsies was performed. Behavior pattern was described by parents or caregivers. The level of activity was classified as no/occasional agitation, daily agitation, and autoaggressive behavior. RESULTS: The behavioral pattern of the children was most frequently (n = 24) described as "agitated" followed by "autoaggressive" behavior (n = 10). Neither autoaggression nor agitation was less frequent (n = 4). Children with autoaggressive behavior had a significantly higher reflux index compared with the neurologically impaired patients with agitation only (P < .01). The reflux index was significantly higher in children with behavioral abnormalities than in children without abnormalities (P < .0004). In children without agitation or autoaggression, the pH measurements were all normal. Biopsies of esophageal mucosa revealed inflammation in 27 cases (first degree in 9; second degree in 12, and third degree in 6). Patients with autoaggressive behavior and those with agitation only had a significantly higher degree of inflammation compared with children without behavioral abnormalities (1.77 and 1.35 vs 0.25, respectively; P < .05). The degree of inflammation did not differ significantly among children with behavioral abnormalities. DISCUSSION: The present study suggests that in children with severe neurologic impairment, autoaggressive behavior or considerable agitation may be a marker for reoccurring or first-time-diagnosed pathologic GER. The severity of reflux correlates significantly to the behavior pattern resulting from experiencing pain. Pathologic GER should be excluded in all neurologically impaired children with behavioral abnormalities to prevent reflux-related complications and improve health-related quality of life. PMID- 17848236 TI - Minimally-invasive pediatric surgery in 2004: a survey including 50 German institutions. AB - BACKGROUND: A survey on the practice of laparoscopic and thoracoscopic surgery in pediatric surgical departments in Germany is presented. MATERIALS AND METHODS: A questionnaire was sent to all 71 pediatric surgical departments in Germany (population 82 million). Fifty institutions (70%) took part in the survey that mainly included data for the year 2004: spectrum of minimally invasive operations, quantity of procedures, conversions, major complications, number of performing surgeons and residents. RESULTS: Laparoscopic techniques were used in 48 departments (96%) and thoracoscopic techniques in 37 (74%). The annual frequency of laparoscopies was less than 100 in 30 departments (62%) and more than 100 in 15 (31%). The number of thoracoscopies was less than 50 in 35 departments (73%) and more than 50 in 2 (4%). Appendectomy was offered in 45 (90%), varicocelectomy in 32 (64%), and Fowler-Stephens operation in 33 (66%). Twenty-one departments (42%) covered more advanced procedures such as laparoscopically assisted pull-through for Hirschsprung disease. Most demanding procedures such as laparoscopic choledochal cyst resection, duodeno-duodenostomy, heminephrectomy, or pyeloplasty were offered by 10 departments (20%). Minimally invasive surgery was performed by 1 surgeon (12%) in 6 institutions and by more than 5 surgeons (14%) in 7 institutions. CONCLUSION: Minimally invasive techniques are increasingly accepted in most German pediatric surgical institutions for a wide range of indications. However, the number of departments offering major minimally invasive procedures remains limited. PMID- 17848237 TI - Respiratory distress in Pierre Robin: successful use of pharyngeal tube. AB - BACKGROUND/PURPOSE: The study describes a safe and least aggressive method to resolve airway obstruction in children born with a Pierre Robin sequence (PRS). METHODS: In a retrospective study, we analyzed the assessment of airway obstruction at birth and for the following months. The definition of PRS was based on the anatomical anomaly triad cleft palate, micro/retrognathia, and glossoptosis with some degree of airway obstruction. We defined 3 categories of children depending on their difficulties of breathing or eating at birth. RESULTS: From 1984 to 2004, 48 children were born in our hospital with a diagnosis of PRS. There were 32 children with nonsyndromic PRS (nsPRS) and 16 with syndromic PRS (sPRS): respectively, 40% (13) and 32% (5) had slight respiratory and/or feeding problems; 26% (8) and 56% (9), isolated feeding difficulties; 34% (11) and 12% (2), severe respiratory and feeding problems. Pharyngeal tube was used in 8 children with nsPRS and in 2 with sPRS. Neonatal surgery was not necessary. Primary palatoplasty was performed at almost the same time as for the patients with isolated cleft palate. CONCLUSIONS: Children born with PRS have a good prognosis at birth provided that adequate respiratory support is given using either positive airway pressure mask or pharyngeal tube. PMID- 17848238 TI - Routine interval appendectomy in children is not indicated. AB - BACKGROUND: This study evaluates outcomes for children treated without interval appendectomy (IA) after successful nonoperative management of perforated appendicitis. METHODS: A retrospective study of pediatric patients with appendicitis was performed from 12 regional acute-care hospitals from 1992 to 2004 with mean length of follow-up of 7.5 years. Main outcomes were recurrent appendicitis and cumulative length of hospital stay. RESULTS: The study included 6439 patients, of which 6367 (99%) underwent initial appendectomy. Seventy-two (1%) patients were initially managed nonoperatively and 11 patients had IA. Of the remaining 61 patients without IA, 5 (8%) developed recurrent appendicitis. Age, sex, type of appendicitis, and abscess drainage had no influence on recurrent appendicitis. Cumulative length of hospital stay was 6.6 days in patients without IA, 8.5 days in patients with IA, and 9.6 days in patients with recurrent appendicitis. CONCLUSION: Recurrent appendicitis is rare in pediatric patients after successful nonoperative management of perforated appendicitis. Routine IA is not necessarily indicated for these children. PMID- 17848239 TI - Pneumatic reduction of childhood intussusception. Is prediction of failure important? AB - BACKGROUND/PURPOSE: Exclusion criteria for enema reduction of intussusception are still a matter of debate. The current study aimed to search for risk factors and to design and evaluate a predictive model of air enema failure. METHODS: The design was a cross-sectional study. The study was conducted at a tertiary university hospital. The participants were 164 children (mean [SD] age of 11.6 [10.7] months) with intestinal intussusception. The intervention done was pneumatic reduction only contraindicated in case of peritonitis and/or sepsis. For main outcome measures, logistic regression analysis was used to estimate the contribution of clinical parameters (age, sex, weight, clinical evolution, temperature, rectal bleeding, white blood cell count, and neutrophils) to predict the risk of enema failure. To evaluate the discriminating power of the model, a receiver operating characteristic curve was constructed, and the effectiveness at different cutoffs was calculated. RESULTS: Overall efficacy was 85%; manual reduction was performed in 12 (7.3%) cases, and there were 9 (6.5%) recurrences. Multivariable analysis adjusted for age and sex revealed that delayed diagnosis (evolution >24 hours) and raised neutrophils (%) were associated with failure: odds ratio of 11.52 (95% CI, 3.73-35.54) and 1.06 (95% CI, 1.02-1.11), respectively. The area under the receiver operating characteristic curve was 0.826 (95% CI, 0.740-0.912). At the best cutoff (0.15), the positive predictive value was 35% and the negative 93%. At the cutoff of 0.50, the positive predictive value was 70% and the negative 87%; the sensitivity was 29%. CONCLUSIONS: The efficacy and safety of pneumatic reduction in childhood intussusception was confirmed. Delayed diagnosis and neutrophils significantly predict outcome. Despite consistent high negative predictive values, the model has low effectiveness in predicting enema failure and may not be clinically relevant; there is no rationale for stricter exclusion criteria. PMID- 17848240 TI - Familial intussusception. AB - PURPOSE: Intussusception is one of the common causes of intestinal obstruction in early childhood. Although a genetic predisposition has been suggested in some cases, its etiology is considered to be incidental, and it has not been traditionally regarded as having any genetic basis. Authors report on cases of so called idiopathic intussusception that demonstrate a strong familial tendency. MATERIALS: We reviewed medical records of idiopathic intussusception reduced in our institute between 1975 and 2004. There were 564 patients. Their parents and/or grandparents were interviewed directly or by telephone about the occurrence of familial intussusception. RESULTS: A family history of idiopathic intussusception, including third-degree relatives, was noted on 39 pedigrees. Occurrences between father and son were 1, mother and son 4, mother and daughter 2, mother and son and daughter 1 (sibling), siblings 10, sibling and cousin 1, uncle or aunt and nephew or niece 6, uncle and nephew and niece (cousin) 1, and cousins 13. Among 564 patients with idiopathic intussusception, 20 patients, both of 6 pairs of siblings and both of 4 pairs of cousins were treated in our institute. So in 554 pedigrees of idiopathic intussusception, the incidence of familial intussusception, including third-degree relatives, was estimated to be 7.0% or 1 in 14.2 cases. CONCLUSION: We concluded that hereditary predisposition, such as anatomical basis, may be considered as an etiological factor in many cases of idiopathic intussusception. In these predisposed families, if they have inducements such as viral infections as the acquired agents, intussusception will occur very easily. PMID- 17848241 TI - New hypothesis on the pathogenesis of ileocecal intussusception. AB - PURPOSE: Ileocecal intussusception is a relatively common surgical emergency in infants and young children. The etiology of intussusception is not clearly understood. Nitric oxide (NO) is a major inhibitory neurotransmitter in the enteric nervous system, which causes relaxation of the smooth muscles. In a lipopolysaccharide-induced experimental model of intussusception, altered intestinal motility is shown to be the result of increased NO released from various inflammatory mediators, which in turn leads to increased incidence of intussusception. The aim of this study was to examine the age-related changes in the nitrergic innervation of the ileocecal valve (ICV) to gain insights into the pathogenesis of intussusception. METHOD: Whole-mount preparations of the myenteric plexus from the ileum, ICV, and proximal colon were stained using NADPH diaphorase histochemistry in newborn piglets (n = 3), 4-week-old (n = 3), 12-week old (n = 3), and adult pigs (n = 3). Using light microscopy, the number of ganglia per square centimeter, the number of cells per ganglion, and the number of ganglion cells per square centimeter were determined. RESULTS: There were striking regional and age-related differences in nitrergic innervation of myenteric plexus. Density of nitrergic neurons was significantly higher in the ICV than in the terminal ileum and proximal large bowel in the young animals (P < .001). CONCLUSION: These findings suggest that the inflammatory reactions that usually precede intussusception may cause overproduction of NO by the nitrergically hyperinnervated ICV causing relaxation of the ICV and thereby facilitating ileocecal intussusception. PMID- 17848242 TI - Risk stratification of 4344 patients with gastroschisis into simple and complex categories. AB - BACKGROUND: Gastroschisis is a congenital full-thickness abdominal wall defect characterized by the protrusion of intraabdominal organs outside the abdominal domain that requires surgical management in the early neonatal period. The goal of this study was to validate a previous risk stratification classification of infants born with this defect. METHODS: A retrospective analysis of a nonoverlapping combination of the databases National Inpatient Sample and Kids' Inpatient Database (1988-2003) was performed. These combined databases contain information from nearly 93 million discharges in the United States. Infants with gastroschisis were identified by an International Classification of Diseases, Ninth Revision procedure code of 54.71 (repair of gastroschisis) and an age at admission of less than 8 days. Infants were divided into simple and complex categories based on the absence or presence of intestinal atresia, stenosis, perforation, necrosis, or volvulus. Variables of sex, race, geographic region, coexisting diagnoses, hospital type and charges adjusted to 2005 dollars, length of stay, inpatient mortality, and complications were collected. Comparison between the 2 groups was performed using Pearson chi2 for categorical outcomes and the Kruskal-Wallis test for non-normally distributed continuous variables. RESULTS: A total of 4344 infants with gastroschisis were identified and divided into simple and complex categories. Simple gastroschisis represented 89.1% (n = 3870) of the group, whereas 10.9% (n = 474) had complex disease. Simple and complex patients differed in coexisting cardiac disease (8.3% vs 11.8%, P = .01), hospital type (78.7% vs 84.1% treated at urban teaching centers, P < .01), median length of stay (28 vs 67 days, P < .01), median inflation-adjusted hospital charges ($90,788 vs $197,871; P < .01), and inpatient mortality (2.9% vs 8.7%, P < .01). Gastrointestinal (14.4% vs 83.5%, P < .01), respiratory (2.6% vs 4.6%, P = .01), and infectious disease complications (24.3% vs 45.4%, P < .01) also differed between the groups. CONCLUSIONS: These data use the largest data set to date to validate the risk stratification of infants with gastroschisis. This analysis improves the characterization and understanding of clinical subsets of infants in whom this congenital condition is diagnosed. PMID- 17848243 TI - Retrospective study of 111 cases of congenital diaphragmatic hernia treated with early high-frequency oscillatory ventilation and presurgical stabilization. AB - BACKGROUND: The prognosis of babies with congenital diaphragmatic hernia (CDH) remains unsatisfactory despite recent advances in medical and surgical treatment. Most authors agree that the best way to improve outcomes for this disease is to focus on pulmonary hypoplasia and persistent pulmonary hypertension (PPH), the 2 most unfavorable prognostic factors for patient survival. However, controversy remains regarding the best treatment of CDH. In the past decade, several institutions have developed treatment protocols that include high-frequency oscillatory ventilation (HFOV), preoperative stabilization, and no thoracic drain. This strategy is 1 of several "gentle ventilation" strategies. We describe our 10-year experience in treating a cohort of 111 infants with CDH managed with this "gentle ventilation" strategy. METHODS: From October 1994 to June 2005, 111 babies with CDH were treated at our institution with HFOV. Babies progressed to inhaled nitric oxide and extracorporeal membrane oxygenation if severe PPH persisted. After a period of preoperative stabilization, surgery was performed via an abdominal approach. In case of large defects or diaphragmatic agenesis, a prosthetic patch was used. No thoracic drain was left in place at the end of surgery. The charts of all babies were reviewed. General characteristics, respiratory management, as well as perioperative and postoperative data were analyzed and correlated with survival. Predicted and actual survival rates in high-, intermediate-, and low-risk groups were analyzed on the basis of the equation described by the Congenital Diaphragmatic Hernia Study Group in 2001. RESULTS: The overall survival rate in our group of patients with CDH was 69.4% regardless of side of the defect. Incidence of a prenatal diagnosis before the 25th gestational week, coexistence of severe congenital heart disease (overall incidence, 5.4%), or other major associated anomalies, as well as the presence of a diaphragmatic agenesis were significantly higher in nonsurvivors. Thirty-six had severe PPH, of which 26 (76.5% of nonsurviving patients) died. Survivors and nonsurvivors had significant differences in blood gas analysis and respiratory management data recorded before and after the diaphragmatic correction. Ninety nine (89%) patients underwent correction of the diaphragmatic defect. A patch was used in 44 (44%) patients and 15 of them died (survivors, 37.7%; nonsurvivors, 68.2%; P = .0111). Six (43%) of 14 patients with a preoperative pneumothorax (survivors, 10.3%; nonsurvivors, 27.3%; P > .05) and 7 (58%) of 12 patients with a postoperative pneumothorax needing a thoracic drain (survivors, 6.5%; nonsurvivors, 31.8%; P = .0013) died. In all cases, pneumothorax was ipsilateral. Two patients required oxygen therapy at discharge. The predicted survival rate was 69%; there was no difference between predicted and actual overall survival as well as between predicted and actual survival in low-risk (predicted survival rate, >66%), intermediate-risk (predicted survival rate, 34%-66%), and high-risk (predicted survival rate, <33%) groups. CONCLUSIONS: The CDH treatment strategy that includes HFOV, preoperative stabilization and no thoracic drain ensures survival with minimal pulmonary morbidity (low rate of pulmonary infections and low rate of patients requiring oxygen at home) in most affected babies. Persistent pulmonary hypertension has been the most challenging factor that ultimately determined the final outcome, and availability of new vasoactive drugs is mandatory to ameliorate the prognosis especially in high-risk patients. Meanwhile, survival comparisons of low-, intermediate-, and high-risk groups between institutions using different protocols will allow the identification of the best strategy for CDH management. PMID- 17848244 TI - Prenatal diagnosis of congenital diaphragmatic hernia: how should the babies be delivered? AB - Congenital diaphragmatic hernia (CDH) in many patients is diagnosed in utero. In these patients, the delivery can be planned as an elective cesarean, induced vaginal, or spontaneous vaginal delivery. The optimal method has yet to be determined. The aim of this study was to compare the outcome of patients with CDH delivered by different methods. METHODS: The Congenital Diaphragmatic Hernia Study Group was formed in 1995 to compile data on liveborn babies with CDH. Beginning in 2001, data concerning delivery were collected. By October 2005, delivery data were available on 1039 term and near-term infants without cardiac malformations. Five hundred forty-eight had a prenatal diagnosis and complete data on delivery (194 delivered by elective cesarean delivery, 121 by induced vaginal delivery, and 233 by spontaneous vaginal delivery). Patients delivered by a nonelective cesarean delivery were assigned to the delivery group for which they were originally planned. RESULTS: The overall survival among the 548 patients was 69%. It was highest in patients delivered by cesarean delivery (71%) followed by those delivered through induced vaginal delivery (70%) and spontaneous vaginal delivery (67%). The difference was not statistically significant. Fifty-three percent of all patients survived without extracorporeal membrane oxygenation (ECMO). This was significantly higher after cesarean delivery (60%) than after induced vaginal delivery (49%) or spontaneous vaginal delivery (49%) (P < .05). At 30 days of age, 45% of the patients delivered by cesarean delivery had survived and were on room air. This was slightly lower after induced vaginal delivery (37%) or after spontaneous vaginal delivery (37%), although not statistically significant. CONCLUSION: Cesarean delivery was associated with a slightly better outcome in terms of a significantly higher survival without the use of extracorporeal membrane oxygenation, although there was no significant difference in total survival. Because this study was not randomized, it is not possible to determine if the elective cesarean delivery was the cause for the better outcome or if centers favoring elective cesarean delivery by protocol are more skillful in the management of patients with CDH. Mode of delivery for term and near-term infants with CDH deserves further prospective study. PMID- 17848245 TI - Congenital hernia of Morgagni in infants and children. AB - BACKGROUND: Congenital Morgagni hernia (CMH) is very rare, comprising 3% to 5% of all types of congenital diaphragmatic hernia; and very little is written about it. Commonly, it is diagnosed during childhood but can remain asymptomatic till adulthood. In the pediatric age group, the presentation is usually vague and nonspecific leading to delay in diagnosis. PATIENTS AND METHODS: The medical records of all patients with the diagnosis of CMH treated at our hospital were retrospectively reviewed for age at diagnosis, sex, presenting symptoms, associated anomalies, diagnosis, operative findings, treatment, and outcome. RESULTS: During an 18-year period (January 1983 through December 2001), 20 cases with the diagnosis of CMH were treated at our hospital. There were 15 males and 5 females. Their age at time of diagnosis ranged from 28 days to 9 years (mean, 16 months), and most of them (65%) were younger than 1 year. Sixteen of them (80%) presented with recurrent chest infection, which most of them had had since early infancy. In 3 patients, Morgagni hernia was discovered after blunt abdominal trauma in one, after insertion of ventriculoperitoneal shunt in another, and as a result of liver enlargement after splenectomy for beta-thalassemia major in the third. Of the 20 patients, 9 had right-sided Morgagni hernia, 5 had left-sided, and 6 had bilateral hernias. In 4 of those with bilateral hernia, the diagnosis of bilaterality was made at the time of surgery. Associated anomalies were seen in 14 (70%) of our patients. Five (25%) had congenital heart disease, 4 (20%) had malrotation of bowel, and 3 (15%) had Down's syndrome. All our patients were operated on transabdominally (14 upper midline, 5 upper transverse) except for one who had a right thoracotomy. In all 3 was a hernial sac, which was excised, and the defect was repaired using nonabsorbable sutures. The contents of the hernial sac included colon, small intestines, part of the liver, and omentum, with the colon being the most common (80%). There was no mortality, and postoperatively all patients did well. One of our patients required postoperative ventilation for 5 days because of associated lung hypoplasia. CONCLUSIONS: Congenital Morgagni hernia is very rare. The rarity, as well as the vague and nonspecific presentations, contributes to the delay in diagnosis. Commonly, the presentation in the pediatric age group is that of recurrent chest infection and rarely with gastrointestinal symptoms. Physicians caring for these patients should be aware of this, and a high index of suspicion is recommended to obviate delay in diagnosis with its associated morbidity. We advocate surgical repair even in asymptomatic patients. This is to obviate the risk of strangulation and colonic perforation. We also advocate a transabdominal approach via either an upper midline or an upper transverse incision. This allows easy reduction and inspection of contents, allows access and repair of bilateral hernias, and corrects an associated malrotation if present. PMID- 17848246 TI - Quantitative analysis of sacral parasympathetic nucleus innervating the rectum in rats with anorectal malformation. AB - BACKGROUND/PURPOSE: The purpose of this experiment was to identify the neurons in the lumbosacral spinal cord involved in colon-rectal function and to compare normal and anorectal malformation of fetal rats. METHODS: The authors quantified the sacral parasympathetic nucleus (SPN) innervation of the rectum by Fluorogold (FG) (Fluorochrome, Englewood, CO) retrograde tracing experiment in fetal rats with normal and anorectal malformation. Anorectal malformation was induced in rat fetuses by ethylenethiourea (ETU). The number of FG-labeled SPNs was scored and compared between male fetuses with or without malformation in the ETU-fed group and control groups. RESULTS: The number of FG-labeled SPNs in the fetuses without a defect, with ETU injected but without any defects of the anorectum or neural tube, with low-type deformity, and with high-type deformity were (mean +/- SEM) 47.3 +/- 2.9, 45.6 +/- 3.2, 24.2 +/- 3.8, and 8.5 +/- 2.5, respectively. Fluorogold-labeled SPNs in the fetuses with high-type deformity were significantly fewer than those in fetuses without defects (P<.05) and in controls (P < .05). CONCLUSIONS: These findings suggest that defective SPN innervation to the rectum is a primary anomaly that coexists with the alimentary tract anomaly in anorectal malformation during fetal development. The intrinsic neural deficiency is an important factor likely to contribute to poor postoperative anorectal function despite surgical correction of the malformation. PMID- 17848247 TI - Anal endosonography is useful for postoperative assessment of anorectal malformations. AB - AIM: This study aimed to develop and evaluate a scoring system for anal endosonography to assess anal canal structures after repair of anorectal malformations (ARM). METHODS: Forty patients with ARM aged 16 years (range, 1-22 years) and 20 controls aged 17 years (range, 0.5-20 years) were examined. Anal function was assessed clinically and by anal canal manometry. The anal canal structures were imaged by anal endosonography using a 7.5-MHz transducer. A scoring system was developed to assess the anal sphincters as visualized on the endosonographic images. RESULTS: Continence was significantly correlated to anal canal pressures. The estimated extent of muscle defect (measured in quadrants) and the number of disruptions in the internal and external anal sphincters correlated significantly to the rest and squeeze pressures, respectively. Thus, patients (>4 years) with squeeze pressure of less than 80 cm H2O were characterized by more than 1 disruption in the external anal sphincter ring and 2 or more quadrants with scar tissue. CONCLUSION: The extent of scar tissue and the number of disruptions in the anal sphincters correlate with anal canal pressures and continence after ARM repair. Anal endosonography may be used to study the results after different surgical techniques and for prognosis on continence in patients with ARM. PMID- 17848248 TI - The inv mouse as an experimental model of biliary atresia. AB - BACKGROUND/PURPOSE: The causation of biliary atresia (BA) remains unclear. However, ductal plate malformation (DPM), maldevelopment of the intrahepatic bile ducts, is 1 of the preferred theories. The inv homozygous mouse (inv mouse), created by insertional mutagenesis, shows situs inversus and jaundice. This study investigated whether the inv mouse could be an experimental model of human BA. METHODS: In the inv mice (n = 12) and wild-type littermates (n = 12), we examined the liver function and morphologic changes in the biliary tract through serum biochemical study and morphological study. RESULTS: The level of serum total and conjugated bilirubin in the inv mouse was 8.1 +/- 3.8 and 4.4 +/- 2.4 mg/dL, respectively, significantly higher than in the wild type. Macroscopically, 11 (92%) of 12 inv mice had situs inversus, and 3 (25%) of 12 mice had preduodenal portal vein. Histologically, the continuity of the extrahepatic bile duct was preserved. However, DPM, showing proliferative biliary epithelium around the intrahepatic portal vein, was found in the liver of the inv mouse. CONCLUSION: In the inv mouse, the pathologic changes in DPM were found in the intrahepatic biliary system, which were observed in some clinical cases of BA. Therefore, the intrahepatic biliary system of the inv mouse could be an experimental model of human BA with DPM. PMID- 17848249 TI - Scanning electron microscopy of fetal murine myelomeningocele reveals growth and development of the spinal cord in early gestation and neural tissue destruction around birth. AB - BACKGROUND: Previous studies demonstrated that the spinal cord within a fetal myelomeningocele (MMC) lesion suffers progressive destruction during gestation. This study aims at elucidating this pathophysiologic feature on a cellular and ultrastructural level in a model of genetically determined MMC. METHODS: Curly tail/loop tail mouse fetuses at various gestational stages and neonates were analyzed electron-microscopically to document time-point and nature of neural tissue development and pathologic alterations within the MMC. RESULTS: At embryonic day (E) 8.5 and E9.5, round cells displaying multiple microvilli covered the entire region of interest, and some specimens showed initial stages of neurulation. At E10.5, neurulation was terminated in normal animals, whereas the neural placode remained unfolded in MMC fetuses and became distinguishable from adjacent epidermal layers. At E15.5, an apparently normal differentiation was found. Until this time-point, there was no tissue damage or inflammation. Thereafter, increasingly severe tissue alterations were identified with ongoing gestation leading to almost complete loss of neural tissue at birth. CONCLUSION: We show here in fetal mice with MMC that, apart from absent neurulation, growth and development of the otherwise perfectly intact exposed spinal cord appear normal in early gestation, whereas later, the unprotected neural tissue is progressively destroyed. PMID- 17848250 TI - Cell membrane and mitotic markers show that the neonatal rat gubernaculum grows in a similar way to an embryonic limb bud. AB - AIM/BACKGROUND: How the gubernaculum guides the testis into the scrotum remains controversial, with various proposals from passive inversion to active growth. We aimed to determine if the gubernaculum contains an area of active proliferation, such as a "progress zone" in a growing embryonic limb bud, using a fluorescent cell membrane marker, 1,1'-didodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate [DiIC12(3)], to trace cell migration, and 5-bromodeoxyuridine (BUDR) (a thymidine analogue) as a mitotic marker. METHODS: Gubernacula were collected from neonatal male rats (n = 42, day 1-2, Sprague-Dawley) and cultured with calcitonin gene-related peptide (CGRP; 714 nmol/L). 1,1'-didodecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate-coated glass beads (diameter, 150-212 microm) were placed next to the bulb for the first 3 hours. Gubernacula were cultured for 3, 18, and 24 hours, then frozen sections cut and examined by confocal microscopy (wavelength, 549 nm). In a second experiment, pups not exposed to exogenous CGRP (n = 53, day 0, Sprague-Dawley) were injected intraperitoneally with BUDR (50 mg/kg of body weight); gubernacula were collected at 2, 48, 72, and 96 hours postinjection (PI), sectioned, and stained using immunohistochemistry to count the number of BUDR-positive cells per 100 cells (labeling index) in the bulb, cremaster, cord, and epididymis. RESULTS: After 24 hours' culture with CGRP, the bulb showed an oval region (diameter, 300 microm) of high fluorescence, and the cremaster region showed elongated cells migrating out of the bulb. When cultured without CGRP, the same oval region contained no fluorescence. In vivo BUDR labeling index increased in all areas until 48 hours postinjection and then decreased most rapidly in the bulb (P < .05), in the presence of endogenous CGRP from the genitofemoral nerve. CONCLUSIONS: The rat gubernaculum contains a putative progress zone, such as in a growing limb bud, in the presence of CGRP. Cells migrate out of this zone to form cremaster muscle. We hypothesize that proliferation in the bulb elongates the gubernaculum, whereas proliferation of cremaster cells would increase gubernacular diameter. This brings to "life" the gubernaculum as an actively growing organ in contrast to the inert ligament connecting the testis to the scrotum portrayed in most anatomy textbooks. PMID- 17848251 TI - Clinical features of testicular torsion and epididymo-orchitis in infants younger than 3 months. AB - BACKGROUND/PURPOSE: Testicular torsion (TT) and orchitis/epididymo-orchitis (EO) are confusing and difficult for physicians to diagnose in infants younger than 3 months. The aim of the study was to delineate the etiology and the clinical features of TT and EO in this age group. METHODS: During the period between April 1994 and September 2004, medical charts of infants younger than 3 months with TT and EO were reviewed retrospectively. RESULTS: Sixteen patients were eligible for the study, including 9 with TT and 7 with orchitis/EO. Two infants had postnatal torsion, and the testicles were salvaged by emergent surgery. Eighty-six percent (6/7) of infants with EO/orchitis had either abnormal physical signs (fever or scrotal tenderness) or abnormal laboratory findings (leukocytosis or elevated C reactive protein level). The sensitivity of color Doppler ultrasound to diagnose TT and EO/orchitis was 88% (7/8) and 100% (6/6), respectively. All infants (6/6) with EO/orchitis who were checked for urinary tract infection and sepsis had positive test results. CONCLUSIONS: Pediatricians should examine the testicles meticulously after a baby is born. Orchitis/EO is highly suspected for patients associated with abnormal physical signs and laboratory findings. Prompt prescription of antibiotics is mandatory to avoid serious sequelae. PMID- 17848252 TI - Oophorectomy in McCune-Albright syndrome: a case of mistaken identity. AB - OBJECTIVE: The objective of the study was to determine the incidence of oophorectomy in girls presenting with precocious puberty and vaginal bleeding who are subsequently diagnosed with McCune-Albright syndrome (MAS). STUDY DESIGN: Medical records of girls diagnosed with MAS between 1988 and 2005 were reviewed. Variables analyzed included presenting features, presence of cafe au lait macules, presence of fibrous dysplasia, radiographic studies, estradiol levels, tumor markers, surgery, and pathology reports. RESULTS: Nine girls with MAS were identified. Average age at initial presentation was 3.2 +/- 2.1 years (range, 0.6 7 years). All patients presented with sudden onset of vaginal bleeding. Eight (88%) also had breast development and 2 (22%) had associated pubic hair. Four (44%) girls underwent salpingo-oophorectomy before the diagnosis of MAS was made. Of these, 3 had cafe au lait macules on initial presentation, and 3 were later diagnosed with fibrous dysplasia. Surgical pathology revealed benign ovarian cysts in all 4 patients. CONCLUSION: Unnecessary oophorectomy is common in girls with MAS who are taken to the operating room for a presumed ovarian tumor. This highlights the need for increased awareness of MAS among pediatricians, pediatric surgeons, and emergency room physicians. Distinguishing features, which can be helpful in differentiating these 2 conditions, are often present. PMID- 17848253 TI - Pin tract infection with external fixation of pediatric fractures. AB - BACKGROUND: This study aimed to evaluate the incidence and severity of pin tract infections in a series of pediatric trauma patients. METHODS: All pediatric trauma patients with external fixation who were treated at our institution between 1998 and 2003 were included. The charts of 30 children (20 males; 10 females; mean age, 13.2 years; range, 7-19 years) with 37 episodes of external fixation were reviewed. The average duration of external fixation was 17.5 weeks (range, 1-94 weeks). Pin tract infections were graded using the Dahl classification. Bacterial cultures were obtained in case of drainage from the pin site. RESULTS: In 18 (48%) of 37 external fixations, no signs of infection occurred during the treatment period. In the remaining 19 (52%) external fixations, 35 episodes of infection were documented. Most infections were mild or moderate, whereas only 3 (9%) severe deep infections were noted (grade 5). Six (17%) infections healed with local application of rifamycin, whereas 27 (77%) of 35 infections were successfully treated with systemic antibiotics (cefuroxime, clindamycin). The remaining 2 infections (6%) required removal of a pin. CONCLUSIONS: Pin tract infection occurred in half of the patients who were treated with external fixations. Most of the pin site infections in the present series were mild and could be managed by local or systemic application of antibiotics. The occurrence of pin tract infections did not require a change of the method of stabilization. PMID- 17848254 TI - Performance of abdominal ultrasonography in pediatric blunt trauma patients: a meta-analysis. AB - OBJECTIVE: The objective of the study was to obtain the best estimates of the test performance of abdominal ultrasonography (US) for identifying children with intraabdominal injuries (IAIs). METHODS: We gathered studies on the use of abdominal US in injured children from the following sources: a MEDLINE and Embase search, hand searches of 5 specialty journals and 4 clinical textbooks, the bibliographies of all identified articles, and contact with experts. Both prospective and retrospective studies were included if they used abdominal US for the detection of intraperitoneal fluid or IAIs in blunt trauma patients less than 18 years of age. All authors independently abstracted data from the selected studies. Disagreements between abstractors were resolved by mutual agreement. RESULTS: Twenty-five articles met the inclusion criteria, and 3838 children evaluated with abdominal US were included. Abdominal US had the following test characteristics for identifying children with hemoperitoneum: sensitivity, 80% (95% confidence interval [CI] 76%-84%); specificity, 96% (95% CI 95%-97%); positive likelihood ratio, 22.9 (95% CI 17.2-30.5); and negative likelihood ratio, 0.2 (95% CI 0.16-0.25). Using the most methodologically rigorous studies, however, yielded the following test characteristics of abdominal US for identifying children with hemoperitoneum: sensitivity, 66% (95% CI 56%-75%); specificity, 95% (95% CI 93%-97%); positive likelihood ratio, 14.5 (95% CI 9.5 22.1); and negative likelihood ratio, 0.36 (95% CI 0.27-0.47). CONCLUSIONS: Abdominal US has a modest sensitivity for the detection of children with hemoperitoneum; however, its test performance characteristics worsen when only the most methodologically rigorous articles are included. A negative US examination has questionable utility as the sole diagnostic test to rule out the presence of IAI. Because of the high risk of IAI, a hemodynamically stable child with a positive US examination should immediately undergo abdominal computed tomographic scanning. PMID- 17848255 TI - The use of preoperative chemotherapy in Wilms' tumor with contained retroperitoneal rupture. AB - PURPOSE: The National Wilms Tumor Study currently describes 3 indications for the use of preoperative chemotherapy: extensive caval involvement, bilateral tumors, and patients who only have a single kidney. However, the management of patients who present with a contained retroperitoneal rupture is not specifically addressed. This is relevant because of the strong possibility of peritoneal contamination when performing a primary resection and the resultant requirement for total abdominal radiation. The use of neoadjuvant chemotherapy in this subgroup of patients may be warranted. METHODS: We retrospectively reviewed our experience with Wilms' tumor and identified 3 cases with contained rupture at presentation. Details of their initial evaluation and therapy, resection and pathologic findings, and follow-up constitute this report. Institutional review board waiver was obtained for the purposes of this review. RESULTS: Two male patients, aged 2.9 years, and 1 female patient, aged 9.3 years, were identified. All patients received preoperative chemotherapy with vincristine and dactinomycin (n = 1) plus doxorubicin (n = 2) for 4 to 6 weeks before surgical resection. One patient underwent pretreatment computed tomography-guided biopsy of the kidney mass for diagnostic purposes. Presurgical computed tomographic scans showed resolution of perinephric blood and fluid with tumor shrinkage. Histopathologic analyses showed all tumors were resected with negative margins, and there was no intraoperative tumor spillage. All patients received 1050 to 1080 cGy of flank radiation postoperatively. All patients are currently alive at follow-up without evidence of local recurrence or distant disease. CONCLUSIONS: Neoadjuvant chemotherapy allowed for complete resection and avoidance of total abdominal radiation in 3 patients with ruptured Wilms' tumor and hematoma within the retroperitoneum. These data support the use of initial chemotherapy in children with retroperitoneal rupture and hematoma of Wilms' tumor at diagnosis. PMID- 17848256 TI - Congenital immature teratoma originating from the jejunum. AB - A small bowel teratoma has never been reported in English literature. We present a case of congenital immature teratoma originating from the jejunum, along with a discussion of its pathophysiologic features and the clinical course. PMID- 17848257 TI - Transection of the stomach after blunt injury in the pediatric population. AB - The incidence of gastric rupture after abdominal blunt injury ranges between 0.02% and 1.7% and is associated with a high morbidity (Tejerina Alvarez EE, Holanda MS, Lopex-Espadas F, Dominguez MJ, Ots E, Diaz-Reganon J. Gastric rupture from blunt abdominal trauma. Injury. 2004;35:228-231, Allen GS, Moore FA, Cox CS. Hollow visceral injury and blunt trauma. J Trauma. 1998;45:69-75.). Stomach transection represents an even rarer type of blunt gastric injury. Although not specifically included in the accepted classification of stomach injury, its clinical manifestation is dramatic, requiring immediate surgical management. We present a case report from our institution and reviewed the international literature focusing on the pediatric patient to illustrate this injury in terms of mechanism of injury, clinical presentation, and surgical management. PMID- 17848258 TI - Morgagni hernia mimicking pneumonia in Down syndrome. AB - Down syndrome patients are immunodeficient and commonly suffer from respiratory infections. Two children with Down syndrome were referred for evaluation of recurrent pneumonia accompanied by persistent infiltrate on chest radiographs. In both cases the radiographic abnormalities were actually found to be Morgagni hernia. When a child with Down syndrome has a persistent lower lobe infiltrate on chest radiograph, the possibility of a diaphragmatic defect should be entertained. PMID- 17848259 TI - Vaginal reconstruction using urinary bladder flap in a patient with cloacal malformation. AB - We report a case of vaginal reconstruction using a flap from urinary bladder in a young girl. This girl was born with cloacal malformation and hemivaginas connected to the urinary bladder. Repeated urinary tract infection and vesicoureteral reflux were noted. At the age of 9 months, she received posterior sagittal anorectoplasty for rectum pull-through, but the urogenital part was not corrected. She had repeated urinary tract infection. Detrusor areflexia and large bladder volume were demonstrated by cystometry. Cystoscopy showed a common channel longer than 3 cm. Urogenital reconstruction was performed at 14 months of age. A part of the urinary bladder wall, which was connected to the vaginas, was used to lengthen the vagina so that the latter was able to pull down to the perineum. The patient received vaginal dilatation and intermittent catheterization after the surgery. PMID- 17848260 TI - Thoracoscopic repair of a type D esophageal atresia in a newborn with complex congenital heart disease. AB - This report describes a case of thoracoscopic repair of esophageal atresia with a rare type D tracheoesophageal fistula in a child with complex congenital heart disease. We demonstrate the feasibility of thoracoscopic repair and anesthetic management in a child with complex congenital heart disease. PMID- 17848261 TI - Case report: Crossed testicular ectopia. AB - Crossed testicular ectopia is a rare congenital anomaly in which both testes descend through a single inguinal canal. The typical presentation is that of ipsilateral inguinal hernia and contralateral cryptorchidism. This is a case report of crossed testicular ectopia in a 6-month-old male infant with depiction of herniorrhaphy and laparoscopic intraabdominal findings. PMID- 17848262 TI - Medullary thyroid carcinoma in a 2-month-old male with multiple endocrine neoplasia 2B and symptoms of pseudo-Hirschsprung disease: a case report. AB - A 5-week-old male patient was seen for symptoms suggestive of Hirschsprung disease (abdominal distension, failure to thrive, and explosive defecation). Rectum biopsies revealed an intestinal ganglioneuromatosis, which is usually associated with multiple endocrine neoplasia (MEN) syndrome type 2B. The ensuing molecular genetic analysis revealed a M918T mutation of the RET protooncogene, which is associated with early-onset medullary thyroid carcinoma (MTC). Therefore, total thyroidectomy and central lymphadenectomy were performed at the age of 9 weeks. Histology showed a medullary microcarcinoma. This report of MTC occurrence within the first weeks of life underlines the importance of early diagnosis and thyroidectomy in patients with MEN 2B syndrome. Because many patients with MEN 2A and B show gastrointestinal symptoms before the development of MTC, the possibility of MEN 2 should be recognized, and genetic testing for the presence of RET mutations should be included in the explorative diagnosis for megacolon. PMID- 17848263 TI - Extralobar pulmonary sequestration mimicking neuroblastoma. AB - Extralobar pulmonary sequestration is a congenital pulmonary malformation, which rarely may be present in an intra-abdominal location. We describe a 1-week-old newborn with an intra-abdominal sequestration, which presented to us as an antenatally diagnosed suprarenal mass. Intra-abdominal extralobar sequestration should also be kept in differential diagnosis in cases of masses in the suprarenal location. PMID- 17848264 TI - A longitudinal study of children treated with the most common form of esophageal atresia and tracheoesophageal fistula. PMID- 17848265 TI - Re: Which is better for esophageal substitution in children, esophagocoloplasty or gastric transposition? A 27-year experience of a single center. PMID- 17848268 TI - Hemangiomas and vascular malformations of the stomach. PMID- 17848271 TI - The 2007 Inaugural ASTRO/ASCO/AHNS Multidisciplinary Head and Neck Cancer Symposium. PMID- 17848272 TI - Gene expression profiles as markers of aggressive disease-EGFR as a factor. PMID- 17848273 TI - Targeting apoptosis to overcome cisplatin resistance: a translational study in head and neck cancer. AB - PURPOSE: Cisplatin resistance remains a barrier to organ-sparing and survival of patients with advanced head and neck squamous cell carcinoma (HNSCC). Targeted therapies to overcome cisplatin-resistant HNSCC are being developed. METHODS AND MATERIALS: Cisplatin-sensitive parental HNSCC cell lines and cisplatin-resistant progeny were studied. Pretreatment HNSCC biopsies were used to construct tissue microarrays which were stained for p53 and Bcl-xL. RESULTS: HNSCC cell lines selected for cisplatin resistance had wild-type p53 and high levels of Bcl-xL. Expression of wild-type p53 in cell lines with low Bcl-xL enhanced cisplatin sensitivity. Expression of both Bcl-xL and wild-type p53 caused tumor cells to become cisplatin resistant. Patients whose tumors expressed low levels of p53 and Bcl-xL enjoyed the best organ preservation and disease-free survival whereas patients whose tumors expressed low levels of p53 and high levels of Bcl-xL had the worst outcome. Novel agents that inhibit Bcl-xL or activate p53 function may target cisplatin-resistant HNSCC. CONCLUSION: Cisplatin resistance in HNSCC is mediated, at least in part, by high Bcl-xL and functional p53. PMID- 17848275 TI - Meta-Analyses of Chemotherapy in Head and Neck Cancer (MACH-NC): an update. PMID- 17848276 TI - Nasopharyngeal cancer: advances in radiotherapy. PMID- 17848274 TI - Response to therapy and outcomes in oropharyngeal cancer are associated with biomarkers including human papillomavirus, epidermal growth factor receptor, gender, and smoking. AB - Induction chemotherapy and concurrent chemoradiation for responders or immediate surgery for non-responders is an effective treatment strategy head and neck squamous cell carcinoma (HNSCC) of the larynx and oropharynx. Biomarkers that predict outcome would be valuable in selecting patients for therapy. In this study, the presence and titer of high risk human papilloma virus (HPV) and expression of epidermal growth factor receptor (EGFR) in pre-treatment biopsies, as well as smoking and gender were examined in oropharynx cancer patients enrolled in an organ sparing trial. HPV16 copy number was positively associated with response to therapy and with overall and disease specific survival, whereas EGFR expression, current or former smoking behavior, and female gender (in this cohort) were associated with poor response and poor survival in multivariate analysis. Smoking cessation and strategies to target EGFR may be useful adjuncts for therapy to improve outcome in the cases with the poorest biomarker profile. PMID- 17848277 TI - Nasopharynx cancer: therapeutic value of chemoradiotherapy. AB - Nasopharyngeal carcinoma (NPC) is especially responsive to both chemotherapy and radiotherapy. It also exhibits a strong and disappointing tendency to metastasize to both regional lymph nodes and distant sites. Distant relapse in NPC is generally fatal and usually relates to advanced-stage presentation, and especially extensive regional lymph node involvement, but also to the presence of the less-differentiated histologic patterns of disease that predominate in the endemic-disease areas of the world. Recent improvements in survival are likely attributable to the adoption of concurrent chemotherapy as a predominant approach, although distant metastases remain as a significant cause of death. Survival improvements probably do not always relate to the use of chemotherapy. Thus contemporary series enjoy a greater advantage compared with historical results because of advances in tumor imaging and radiotherapy delivery. It is impossible to assess the impact of these parameters on previous trial results, and it remains plausible that outcomes may still be significantly influenced by imprecise radiotherapy targeting. The randomized trials in the English literature designed to address the impact of chemotherapy on the survival of NPC patients are discussed. Potential causes of inconsistencies among trials are outlined, and the results of the only individual patient data meta-analysis are summarized. The discussion concludes with some commentary concerning newer strategies for the management of NPC to address the problem of distant metastases. PMID- 17848278 TI - Multidisciplinary management of laryngeal carcinoma. AB - The management of head and neck cancer has evolved into a multidisciplinary approach in which patients are evaluated before treatment and decisions depend on prospective multi-institutional trials, as well as retrospective outcome studies. The choice of one or more modalities to use in a given case varies with the tumor site and extent, as exemplified in the treatment of laryngeal squamous cell carcinomas. The goals of treatment include cure, laryngeal voice preservation, voice quality, optimal swallowing, and minimal xerostomia. Treatment options include transoral laser excision, radiotherapy (both definitive and postoperative), open partial laryngectomy, total laryngectomy, and neck dissection. The likelihood of local control and preservation of laryngeal function is related to tumor volume. Patients who have a relatively high risk of local recurrence undergo follow-up computed tomography scans every 3-4 months for the first 2 years after radiotherapy. Patients with suspicious findings on computed tomography might benefit from fluorodeoxyglucose positron emission tomography to differentiate post-radiotherapy changes from tumor. PMID- 17848279 TI - Nasopharyngeal cancer: new frontiers from the laboratory to the clinic. AB - Nasopharyngeal carcinoma (NPC) is a unique malignant epithelial carcinoma of the head-and-neck region, with unique viral biology and geographic distributions in the world. Significant advances have been made in the clinical therapies for NPC, with novel techniques for radiation delivery and randomized trials demonstrating the survival advantage of concurrent chemotherapy for patients with locally advanced diseases. At the same time, there has been an improved understanding of the molecular dysregulations underpinning this disease, with recent discoveries emerging from the use of high-throughput technologies, including microarray expression profiling and robotic screens of chemical libraries. Signaling pathways related to cell renewal, proliferation, and apoptosis are important cascades, which could offer potentially novel strategies to develop targeted therapies, with the ultimate aim to improve outcome for future patients with NPC. PMID- 17848280 TI - Robotic anterior and midline skull base surgery: preclinical investigations. AB - PURPOSE: To develop a minimally invasive surgical technique to access the midline and anterior skull base using the optical and technical advantages of robotic surgical instrumentation. METHODS AND MATERIALS: Ten experimental procedures focusing on approaches to the nasopharynx, clivus, sphenoid, pituitary sella, and suprasellar regions were performed on one cadaver and one live mongrel dog. Both the cadaver and canine procedures were performed in an approved training facility using the da Vinci Surgical Robot. For the canine experiments, a transoral robotic surgery (TORS) approach was used, and for the cadaver a newly developed combined cervical-transoral robotic surgery (C-TORS) approach was investigated and compared with standard TORS. The ability to access and dissect tissues within the various areas of the midline and anterior skull base were evaluated, and techniques to enhance visualization and instrumentation were developed. RESULTS: Standard TORS approaches did not provide adequate access to the midline and anterior skull base; however, the newly developed C-TORS approach was successful in providing the surgical access to these regions of the skull base. CONCLUSION: Robotic surgery is an exciting minimally invasive approach to the skull base that warrants continued preclinical investigation and development. PMID- 17848281 TI - Swing of the surgical pendulum: a return to surgery for treatment of head and neck cancer in the 21st century? AB - Treatment for head and neck cancer has evolved significantly during the past 100 years. Beginning with Bilroth's total laryngectomy on New Year's Day in 1873, "radical" surgery remained the only accepted treatment for head and neck cancer when optimal local and regional control was the goal. Bigger was still better when it came to managing the primary tumor and the neck. The "commando" procedure and radical neck dissection were the hallmarks of this first generation of treatments of head-and-neck cancer. With the advent of microvascular reconstructive techniques, larger and more comprehensive resections could be performed. Despite these large resections and their "mutilating" sequelae, overall survival did not improve. Even for intermediate-stage disease in head-and neck cancer, the 5-year survival rate did not improve >50%. Many concluded that more than the scalpel was needed for optimal local and regional control, especially for intermediate- and advanced-stage disease. Most important, the multidisciplinary teams must identify and correlate biomarkers in the tumor and host that predict for a response to therapy and for optimal functional recovery. As the pendulum swings back, a scientific approach using tissue biomarkers for the response to treatment in the setting of multidisciplinary trials must emerge as the new paradigm. In the postgenomic era, treatment decisions should be made based on functional and oncologic parameters-not just to avoid perceived morbidity. PMID- 17848282 TI - Moving toward bioadjuvant approaches to head and neck cancer prevention. AB - Head and neck squamous cell carcinoma affects >45,000 Americans annually. Patients who are successfully treated for their primary tumor are at high risk of developing a second primary tumor, making effective preventive strategies highly desirable for this disease. Although a landmark study in 1990 suggested some benefit of high-dose retinoids in head and neck cancer prevention, subsequent trials using more tolerable doses have shown limited clinical success. Newer preventive strategies have included bioadjuvant therapy combining retinoids with interferon and alpha-tocopherol, combinations of molecularly targeted agents, and oncolytic viruses. Furthermore, considerable evidence has supported a cancer protective role for several nutrients, including green tea and curcumin analogs. Natural compounds such as these with favorable long-term safety profiles might be particularly suited to the cancer prevention setting, in which patients will usually tolerate only moderate risk and toxicity. PMID- 17848283 TI - Surgical approaches to the oral cavity primary and neck. AB - PURPOSE: A variety of surgical approaches used to treat primary oral cavity tumors are described to delineate the technique and rationale behind each treatment choice. METHODS AND MATERIALS: Size, location, proximity to bone, lymph node status, histology, and prior treatment considerations are employed to determine the most appropriate surgical approach for primary oral cavity tumors. RESULTS: Oncologic outcomes and physical function show the best results from surgical treatment of many primary oral cavity, but necessitates careful selection of surgical approach. CONCLUSION: Each surgical approach must be selected based upon relevant tumor, patient and physician factors. PMID- 17848284 TI - Free flaps in oral cavity reconstruction: when you need them and when you don't. PMID- 17848285 TI - Established and emerging concepts in epidermal growth factor receptor biology. PMID- 17848286 TI - Stepwise progress in epidermal growth factor receptor/radiation studies for head and neck cancer. AB - The U.S. Food and Drug Administration approval of four new epidermal growth factor receptor (EGFR) inhibitors for cancer therapy (cetuximab, panitumumab, gefitinib, and erlotinib) over the last 3 years is a remarkable milestone in oncology. Indeed, molecular inhibition of EGFR signaling represents one of the most promising current arenas for the development of molecular-targeted cancer therapies. Epidermal growth factor receptor inhibitors from both the monoclonal antibody and tyrosine kinase inhibitor class have demonstrated clinical activity in the treatment of a broad spectrum of common human malignancies. For the discipline of radiation oncology, the 2006 report of a phase III trial demonstrating a survival advantage for advanced head and neck cancer patients with the addition of weekly cetuximab during a 7-week course of radiation is particularly gratifying. Indeed, this is the first phase III trial to confirm a survival advantage with the addition of a molecular-targeted agent to radiation. Furthermore, this result seems to have been achieved with only a modest increment in overall treatment toxicity and with very high compliance to the prescribed treatment regimen. Nevertheless, much remains to be learned regarding the rational integration of EGFR inhibitors into cancer treatment regimens, as well as methods to optimize the selection of patients most likely to benefit from EGFR inhibitor strategies. PMID- 17848287 TI - Surgery in the management of laryngeal and hypopharyngeal carcinoma. PMID- 17848288 TI - Radiotherapy alone for early-stage squamous cell carcinoma of the larynx and hypopharynx. AB - PURPOSE: To describe and illustrate examples of early-stage larynx and hypopharynx cancer that can be successfully treated with radiotherapy alone. METHODS AND MATERIALS: Review of the NCCN and ASCO practice guidelines. Representative examples are included. RESULTS: Early-stage larynx and hypopharynx cancer is defined by tumor extent based on physical and imaging examination. CONCLUSIONS: Radiotherapy alone is appropriate treatment for properly selected early-stage squamous cell carcinoma of the larynx and hypopharynx. The NCCN and ASCO practice guidelines can be an aid to the clinician in identifying favorable cancers that can be successfully treated with radiotherapy alone with preservation of organ function. PMID- 17848289 TI - Concurrent chemoradiotherapy in the management of squamous cell cancer of the oropharynx: current standards and future directions. PMID- 17848290 TI - Integrating surgery into treatment paradigms for organ preservation: tailoring treatment to biology improves outcomes. AB - PURPOSE: Neoadjuvant chemotherapy was introduced into treatment paradigms for curable head and neck cancer in the early 1970s in an effort to reduce the magnitude of mutilating surgery and to provide a rationale for adjuvant systemic chemotherapy in patients who responded to initial chemotherapy. The large number of trials that followed failed to demonstrate improved survival when neoadjuvant chemotherapy was added to conventional surgery or radiation. Importantly, a consistent observation in these neoadjuvant trials was the significant association of clinical tumor response to neoadjuvant therapy and favorable prognosis. RESULTS: The findings led to development of a new treatment paradigm that was based on the hypothesis that the biology of an individual cancer is more predictive of response to specific therapy and overall outcome than is anatomic tumor site or extent, and on the corollary that matching treatment modality to biology will improve overall survival rates. CONCLUSIONS: This report identifies key findings that are important in the design and analysis of organ preservation trials and biologic markers predictive of response and outcomes. Ongoing studies incorporating biomarkers such as p53, Bcl-xL, HPV, EGFR, COX-2, and tumor promoter gene methylation are underway and will identify new targets for molecular manipulation, response monitoring, and tumor imaging that could allow real-time changes in how we integrate the various components of multi-modal therapy. PMID- 17848291 TI - Can IMRT or brachytherapy reduce dysphagia associated with chemoradiotherapy of head and neck cancer? The Michigan and Rotterdam experiences. AB - PURPOSE: Dysphagia is a major late complication of intensive chemoradiotherapy of head and neck cancer. The initial clinical results of intensity-modulated radiotherapy (IMRT), or brachytherapy, planned specifically to reduce dysphagia are presented. PATIENTS AND METHODS: Previous research at Michigan University has suggested that the pharyngeal constrictors and glottic and supraglottic larynx are likely structures whose damage by chemo-RT causes dysphagia and aspiration. In a prospective Michigan trial, 36 patients with oropharyngeal (n = 31) or nasopharyngeal (n = 5) cancer underwent chemo-IMRT. IMRT cost functions included sparing noninvolved pharyngeal constrictors and the glottic and supraglottic larynx. After a review of published studies, the retropharyngeal nodes at risk were defined as the lateral, but not the medial, retropharyngeal nodes, which facilitated sparing of the swallowing structures. In Rotterdam, 77 patients with oropharyngeal cancer were treated with IMRT, three dimensional RT, or conventional RT; also one-half received brachytherapy. The dysphagia endpoints included videofluoroscopy and observer-assessed scores at Michigan and patient reported quality-of-life instruments in both studies. RESULTS: In both studies, the doses to the upper and middle constrictors correlated highly with the dysphagia endpoints. In addition, doses to the glottic and supraglottic larynx were significant in the Michigan series. In the Rotterdam series, brachytherapy (which reduced the doses to the swallowing structures) was the only significant factor on multivariate analysis. CONCLUSION: The dose-response relationships for the swallowing structures found in these studies suggest that reducing their doses, using either IMRT aimed at their sparing, or brachytherapy, might achieve clinical gains in dysphagia. PMID- 17848292 TI - Intensity-modulated radiation therapy in the treatment of head and neck cancer involving the base of the skull. AB - Tumors invading the skull base pose a difficult problem for the treating radiation oncologist. When confronting these highly complex tumors where the gross tumor abuts the optic apparatus or brain stem, the physician often has to make a difficult choice regarding coverage of the tumor, i.e., underdosing portions of the tumor to protect the critical normal tissues versus accepting the risk of late complication while ensuring full coverage of the tumor. This situation is often encountered in advanced T4 disease originating either in the paranasal sinuses or the nasopharynx. In this case report, the author presents a case in which difficult decisions were made when treating a complex, locally advanced, T4 nasopharyngeal cancer that invaded the skull base. PMID- 17848293 TI - Matching intensity-modulated radiation therapy to an anterior low neck field. AB - When using intensity-modulated radiation therapy (IMRT) to treat head and neck cancer with the primary site above the level of the larynx, there are two basic options for the low neck lymphatics: to treat the entire neck with IMRT, or to match the IMRT plan to a conventional anterior "low neck" field. In view of the potential advantages of using a conventional low neck field, it is important to look for ways to minimize or manage the problems of matching IMRT to a conventional radiotherapy field. Treating the low neck with a single anterior field and the standard larynx block decreases the dose to the larynx and often results in a superior IMRT plan at the primary site. The purpose of this article is to review the most applicable studies and to discuss our experience with implementing a technique that involves moving the position of the superior border of the low neck field several times during a single treatment fraction. PMID- 17848294 TI - Diagnostic difficulties in the classification and grading of salivary gland tumors. PMID- 17848295 TI - Postoperative and primary radiotherapy for salivary gland carcinomas: indications, techniques, and results. PMID- 17848296 TI - Identifying and targeting hypoxia in head and neck cancer: a brief overview of current approaches. PMID- 17848297 TI - Promising new targeted agents in head and neck cancer. PMID- 17848298 TI - Hypoxia in head and neck cancer: studies with hypoxic positron emission tomography imaging and hypoxic cytotoxins. PMID- 17848299 TI - Antiangiogenesis and vascular endothelial growth factor/vascular endothelial growth factor receptor targeting as part of a combined-modality approach to the treatment of cancer. PMID- 17848301 TI - Increasing toxicity in nonoperative head and neck cancer treatment: investigations and interventions. PMID- 17848302 TI - Changes in radiotherapeutic management of head and neck cancer: a 30-year perspective. PMID- 17848303 TI - Integrating palliative care into head and neck oncology. PMID- 17848300 TI - Strategic plans to promote head and neck cancer translational research within the radiation therapy oncology group: a report from the translational research program. AB - Head and neck cancer is the fifth most common cancer in the United States, with an overall survival rate of approximately 40-50%. In an effort to improve patient outcomes, research efforts designed to maximize benefit and reduce toxicities of therapy are in progress. Basic research in cancer biology has accelerated this endeavor and provided preclinical data and technology to support clinically relevant advances in early detection, prognostic and predictive biomarkers. Recent completion of the Human Genome Project has promoted the rapid development of novel "omics" technologies that allow more broad based study from a systems biology perspective. However, clinically relevant application of resultant gene signatures to clinical trials within cooperative groups has advanced slowly. In light of the large numbers of variables intrinsic to biomarker studies, validation of preliminary data for clinical implementation presents a significant challenge and may only be realized with large trials that involve significant patient numbers. The Radiation Therapy Oncology Group (RTOG) Head and Neck Cancer Translational Research Program recognizes this problem and brings together three unique features to facilitate this research: (1) availability of large numbers of clinical specimens from homogeneously treated patients through multi institutional clinical trials; (2) a team of physicians, scientists, and staff focused on patient-oriented head-and-neck cancer research with the common goal of improving cancer care; and (3) a funding mechanism through the RTOG Seed Grant Program. In this position paper we outline strategic plans to further promote translational research within the framework of the RTOG. PMID- 17848304 TI - Dysphagia after chemoradiation: prevention and treatment. PMID- 17848305 TI - Bridging gaps in multidisciplinary head and neck cancer care: nursing coordination and case management. AB - Patients with advanced head and neck cancer face not only a life-threatening malignancy, but also a remarkably complex treatment regimen that can affect their cosmetic appearance and ability to speak, breathe, and swallow. These patients benefit from the coordinated interaction of a multidisciplinary team of specialists and a comprehensive plan of care to address their physical and psychosocial concerns, manage treatment-related toxicities, and prevent or limit long-term morbidities affecting health-related quality of life. Although little has been published on patient-provider communication with a multidisciplinary team, evidence has suggested that gaps often occur in communication between patients and providers, as well as between specialists. These communication gaps can hinder the multidisciplinary group from working toward common patient centered goals in a coordinated "interdisciplinary" manner. We discuss the role of a head-and-neck oncology nurse coordinator at a single institution in bridging gaps across the continuum of care, promoting an interdisciplinary team approach, and enhancing the overall quality of patient-centered head-and-neck cancer care. PMID- 17848306 TI - Treatment of thyroid cancer: 2007--a basic review. PMID- 17848307 TI - Phosphoinositide kinase-3 status associated with presence or absence of human papillomavirus in head and neck squamous cell carcinomas. AB - PURPOSE: To investigate phosphoinositide kinase-3 (PI3K) activation in relation to human papillomavirus (HPV) status in head and neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS: Gene expression microarray data were analyzed to determine differentially expressed genes between HPV(+) and HPV(-) HNSCC. PIK3CA gene expression was confirmed by quantitative reverse transcriptase-polymerase chain reaction in seven HPV(+) and seven HPV(-) primary HNSCCs. PIK3CA mutation status in three HPV(+) and nine HPV(-) cell lines was determined by polymerase chain reaction amplification of hot spot exons (1, 9, 20) followed by direct sequencing. RESULTS: PIK3CA was overexpressed in HPV(+)-associated HNSCC compared with the expression in HPV(-) HNSCC. Activation of PIK3CA by mutation was found in 1 of the 12 tested HNSCC cell lines. CONCLUSION: Activation of PI3K by mutation of PIK3CA is rare in HNSCC cell lines and was not found in three HPV(+) cell lines. One mechanism by which HPV-associated HNSCC might activate PI3K is increased expression of PIK3CA. PMID- 17848308 TI - Jordan Matthew Phillips, MD: visionary, founder of the American Association of Gynecologic Laparoscopists, organizational genius. PMID- 17848309 TI - Bipolar electrosurgery: a short history. PMID- 17848310 TI - Female sterilization's impact on laparoscopy. PMID- 17848311 TI - Putting laparoscopy on the academic map: early and continuing scholarship by the AAGL. PMID- 17848312 TI - The uniqueness of the man. PMID- 17848313 TI - Adenomyosis visualized during hysteroscopy. PMID- 17848314 TI - A rare case of encapsulated caseous ball. PMID- 17848315 TI - Total laparoscopic hysterectomy in cases of very large uteri: a retrospective comparative study. AB - In this review, we assessed the feasibility of total laparoscopic hysterectomy (TLH) in cases of very large uteri weighting more than 500 grams. We compared surgical outcomes and short term follow-up in 149 patients with the uterus weighing less than 350 g (group A: 40-350 g) and 100 patients with the uterus weighing more than 500 g (group B: 500-1550 g). We discovered no statistical difference between the 2 groups in terms of intraoperative complications (group A: 0%; group B: 2%) and postoperative stay (group A: 3.05 +/- 1.89 days; group B: 3.2 +/- 1.28 days). There were statistically significant differences between the 2 groups in terms of operative time (group A: 101.3 +/- 34.3 min; group B: 149.1 +/- 57.2 min.; p <.0001) and postoperative hospital stay length (group A: 2.8 +/- 0.7 days; group B: 3.5 +/- 1.7 days; p <.0001). No major complications occurred in either group. Postoperative minor complications were more frequent in group B (group A: 8.7%; group B: 18%; p = .03). Median time to well-being was comparable in both groups. In conclusion, TLH is a feasible surgical technique also in cases of very large uteri. An increase in operative time, intraoperative blood loss, hospital stay length, and postoperative minor complications can be expected as the uterine weight increases. PMID- 17848316 TI - Rising use of synthetic mesh in transvaginal pelvic reconstructive surgery: a review of the risk of vaginal erosion. AB - Recently, the use of surgical mesh in pelvic floor surgery has become increasingly popular. While the reduction of surgical failure rates in vaginal reconstructive surgery is of critical importance, the addition of graft materials must be shown to improve anatomical outcomes and at least maintain, if not improve, lower urinary tract, bowel, and sexual function, as well as quality of life for the patient. Synthetic materials still have several disadvantages including vaginal erosion. Several factors contribute to the wide range of vaginal erosion rates, including patient characteristics such as age and estrogen deficiency; operative technique; implant size; and the specific properties of the graft material, such as pore size, stiffness, elasticity, and basic tissue compatibility. It is the aim of this article to present a critical review of the risk of vaginal erosion with use of synthetic grafts during vaginal reconstructive surgery. PMID- 17848317 TI - Positive symptom improvement with laparoscopic uterosacral ligament repair for uterine or vaginal vault prolapse: interim results from an active multicenter trial. AB - STUDY OBJECTIVE: To evaluate the use of laparoscopic uterosacral ligament repair for long-term patient symptom improvement in patients with uterine prolapse or posthysterectomy vaginal vault prolapse and to evaluate how laparoscopic instrumentation kits facilitate procedure performance for the surgeon. DESIGN: Nonrandomized, prospective, multicenter case series (Canadian Task Force classification II-2). SETTING: Five clinical sites consisting of 4 community hospitals and 1 university medical center. PATIENTS: Seventy-two patients with stage II or worse uterine prolapse (58%, n = 42) or posthysterectomy vaginal vault prolapse (42%, n = 30). One patient with stage I vaginal vault prolapse was included in the group due to her significant symptoms. INTERVENTIONS: Laparoscopic uterosacral ligament repair was performed on all patients; round ligament truncation was also performed selectively on patients with uterine prolapse. Fifty-seven percent (41 patients) had concomitant pelvic procedures. MEASUREMENTS AND MAIN RESULTS: At 12-month follow-up, Pelvic Organ Prolapse Quantification (POP-Q) scores and patient self-reported symptom scores were significantly improved over baseline after laparoscopic repair of pelvic organ prolapse. Positive mean change in POP-Q score was 14.4 (p = .0003) for uterine prolapse repair and 9.28 (p = .017) for vaginal vault prolapse repair. Positive mean change in total symptom score was 20.36 (p <.0001) for uterine prolapse repair and 11.43 (p = .005) for vaginal vault prolapse repair. Surgeons reported a mean procedure time of 31.6 minutes for uterine prolapse repair and 21.7 minutes for vaginal vault prolapse repair. A mean rating of 7.5 was documented for ease of use for the uterine prolapse kit and 4.1 for the vaginal vault prolapse kit on a scale of 1 to 10. CONCLUSION: Laparoscopic uterosacral ligament repair improves symptoms and POP-Q scores over the long term in patients with uterine or vaginal vault prolapse. Laparoscopic instrumentation kits facilitate procedure performance for the surgeon with expedited surgery times. PMID- 17848318 TI - Laparoscopic sacral colpopexy with Gynemesh as graft material--experience and results. AB - STUDY OBJECTIVE: To evaluate the safety and efficacy of Prolene (Ethicon, Inc., Johnson and Johnson, Somerville, NJ) graft for sacral colpopexy and ease of use laparoscopically. DESIGN: Retrospective analysis (Canadian Task Force classification II-1). SETTING: Academic university hospital. PATIENTS: Seventy four patients with recurrent prolapse of the apex or severe uterine prolapse (stage II-IV). INTERVENTIONS: Seventy-four patients with recurrent prolapse of the apex or severe uterine prolapse (stage II-IV) underwent laparoscopic sacral colpopexy or cervicopexy with Gynemesh (Ethicon, Inc.) used as the graft material. MEASUREMENTS AND MAIN RESULTS: Seventy-four patients, from March 2003 through March 2006, underwent a sacropexy. Fifty-one patients had recurrent apical prolapse, 22 patients had uterovaginal prolapse stage III or IV, and 1 patient had uterovaginal prolapse stage II and insisted on retaining the uterus. Fifty-two patients also had a concurrent sling procedure performed for incontinence. Intraoperative and postoperative complications included 1 middle sacral bleed managed by suturing in the middle sacral region and 1 postoperative cervical abscess requiring reoperation and removal of the graft at 10 days. All patients were evaluated at 2 weeks and 6 weeks after surgery, and pelvic examination was performed. They were then followed up biannually. Median age was 63 years (range 48-76 years), and median body mass index was 35 (range 24-41). Laparoscopic sacral colpopexy or cervico or uteropexy was performed successfully in 72 patients. Median blood loss was less than 25 mL (range 25-150 mL), and the median hospital stay was 1 day (range 1-2 days). One surgery was terminated because of dense rectosigmoid adhesions to the cuff requiring a laparotomy and partial sigmoid resection because of redundancy and postdissection trauma to the sigmoid. Another procedure was completed as a Prolift (Johnson and Johnson) procedure because of finding of a prior Mersilene (Phillips Sumika Polypropylene Co., Houston, TX) mesh that was densely adherent to the pelvic contents. Seventy patients are extremely happy and satisfied with the surgery. Postoperative recovery has been uneventful, and subjective and objective cure is 97% and 100%, respectively. One patient with sacrouteropexy still has stage I prolapse of her cervix, but it feels well supported. There have been no cases of colpopexy graft exposure or recurrence with a median follow-up of 24 months (range 9-36 months). The patient with cervical abscess and graft removal has also healed with no recurrance of her prolapse. CONCLUSIONS: Laparoscopic sacral colpopexy or cervicopexy is a safe and effective procedure with excellent results. Gynemesh (Ethicon, Inc.), a wide-pore polypropelene mesh seems to be an excellent graft material with low risk for graft infection (1.4%) or erosion. PMID- 17848319 TI - Feasibility, morbidity, and safety of total laparoscopic radical hysterectomy with lymphadenectomy: our experience. AB - STUDY OBJECTIVE: The purpose of this study was to retrospectively evaluate, in a series of 65 patients, the feasibility, morbidity, and safety of total laparoscopic radical hysterectomy with lymphadenectomy for early cervical carcinoma. DESIGN: Retrospective, nonrandomized study (Canadian Task Force classification II-2). SETTING: Advanced Gynecological Endoscopy Center, Malzoni Medical Center, Avellino, Italy. PATIENTS: Sixty-five nonconsecutive patients with International Federation of Gynecology and Obstetrics (FIGO) stage Ia1 with lymphvascular space involvement, Ia2, and Ib1 early cervical cancer. INTERVENTION: Fourteen patients underwent a laparoscopic class II procedure, and 51 patients underwent a class III procedure according to the Piver classification. All the patients underwent total laparoscopic radical hysterectomy with pelvic lymphadenectomy during the study period, and none of the surgeries required conversion to laparotomy. Paraaortic lymphadenectomy is not routinely performed unless suspicious pelvic lymph nodes are confirmed to have metastatic disease on frozen section evaluation. MEASUREMENTS AND MAIN RESULTS: Fifty-six patients had squamous cell carcinoma; 7 patients had adenocarcinomas, and 2 had adenosquamous carcinoma. The mean age was 40.5 years (95% CI 27.7-69.1) and the SD was +/- 7.5. The median weight was 56.2 kg (range 44-75 kg). The median operative time was 196 minutes (range 182-240 minutes), and the surgical margins were free of disease in all cases. The median blood loss was 55 mL (range 30-80 mL). No patient required an intraoperative blood transfusion. The median length of hospital stay was 4 days (range 3-7 days). CONCLUSION: Laparoscopic treatment of cervical cancer offers patients the potential benefits of decreased discomfort with decreased convalescence time, but it should be reserved for oncologic surgeons trained in extensive laparoscopic procedures. PMID- 17848320 TI - Efficacy of barriers and hypoxia-inducible factor inhibitors to prevent CO(2) pneumoperitoneum-enhanced adhesions in a laparoscopic mouse model. AB - STUDY OBJECTIVE: To investigate the effects of hypoxia-inducible factor (HIF) inhibitors, flotation agents, barriers, and a surfactant on pneumoperitoneum enhanced adhesions in a laparoscopic mouse model. DESIGN: Prospective randomized trial (Canadian Task Force classification I). SETTING: Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, Catholic University of Leuven. SUBJECTS: One hundred fourteen female BALB/c mice. INTERVENTIONS: Adhesions were induced during laparoscopy in BALB/c female mice. Pneumoperitoneum was maintained for 60 minutes with humidified CO(2). In 3 experiments the effects of HIF inhibitors such as 17-allylamino 17-demethoxygeldanamycin, radicicol, rapamycin, and wortmanin, flotation agents such as Hyskon and carboxymethylcellulose, barriers such as Hyalobarrier gel and SprayGel, and surfactant such as phospholipids were evaluated. MEASUREMENTS AND MAIN RESULTS: Adhesions were scored after 7 days during laparotomy. Adhesion formation decreased with the administration of wortmannin (p <.01), phospholipids (p <.01), Hyalobarrier Gel (p <.01), and SprayGel (p <.01). CONCLUSIONS: These experiments confirm the efficacy of barriers and phospholipids to separate or lubricate damaged surfaces. They also confirm the role of mesothelial hypoxia in this model by the efficacy of the HIF inhibitor wortmannin. PMID- 17848321 TI - Urinary tract injury in laparoscopic-assisted vaginal hysterectomy. AB - STUDY OBJECTIVE: To evaluate the incidence and characteristics of urinary tract injury after laparoscopic-assisted vaginal hysterectomy (LAVH). DESIGN: A retrospective study that evaluated all cases of urinary tract injury at the time of LAVH in an 11-year period. Parameters including surgical indication, site of injury, time of diagnosis, method of treatment, and long-term follow-up were analyzed. (Canadian Task Force classification II-2). SETTING: Tertiary care university hospital. PATIENTS: A total of 38 urinary tract injuries were found in 7725 LAVH. INTERVENTION: LAVH and repair of urinary tract injuries with transvaginal or transabdominal approach. MEASUREMENTS AND MAIN RESULTS: The incidence of urinary tract injury after LAVH was 4.9/1000 procedures: 3.9/1000 for urinary bladder injury and 1.0/1000 for ureteral injury. Prior cesarean section was the most common risk factor for bladder injuries. Ninety-six percent (29/30) of urinary bladder injuries were detected and treated during surgery. Half (4/8, 50%) of the ureteral injuries were identified during surgery. Of the 38 complications, 28 (75.7%) occurred in surgery. CONCLUSION: Most urinary tract injuries in LAVH were identified during surgery and are associated with the surgeon's experience. Bladder injury can be repaired either transvaginally or abdominally; ureteral injury can be repaired abdominally. PMID- 17848322 TI - Endoscopic surgery in patients with borderline tumor of the ovary: a follow-up study of thirty-five patients. AB - STUDY OBJECTIVE: To study the long-term outcome of 35 patients after endoscopic surgery of ovarian borderline tumor. DESIGN: Descriptive study (Canadian Task Force classification II-2). SETTING: Outpatient clinic. PATIENTS: Thirty-five women with histologically proven ovarian borderline tumors underwent adnexal surgery by laparoscopy in an outpatient clinic. INTERVENTIONS: We report a series of 41 patients treated by endoscopic surgery for borderline tumors of the ovary, 35 of whom were followed up for 2 to 12 years after surgery. MEASUREMENTS AND MAIN RESULTS: Of a total of 3138 patients referred for endoscopic surgery to treat ovarian tumors, 7 were found to have cancer, and 41 were found to have borderline tumors. The borderline tumor was diagnosed before surgery by vaginal ultrasonography in 45.7% of patients, during surgery in an additional 22.9%, but only by postoperative histologic study in 31.4% of patients. There were no intraoperative or postoperative complications in the patients with borderline tumor, and all have remained healthy for the period of their follow-up. CONCLUSION: Provided a strict management protocol is followed, endoscopic surgery is safe and effective for the treatment of borderline tumors of the ovary. PMID- 17848323 TI - Laparoscopic-assisted vaginal hysterectomy versus minilaparotomy hysterectomy: a prospective, randomized, multicenter study. AB - STUDY OBJECTIVE: The aim of this study was to compare operative and early postoperative outcomes of laparoscopic-assisted vaginal hysterectomy (LAVH) and minilaparotomy in a randomized clinical trial including patients undergoing total hysterectomy for benign gynecologic disease and having 1 or more of the generally considered contraindications to vaginal route. DESIGN: Prospective, randomized, multicenter trial (Canadian Task Force classification I). SETTING: Departments of Gynecology from 3 major university hospitals in Rome. PATIENTS: Eighty-one patients who were candidates for abdominal hysterectomy. INTERVENTIONS: Laparoscopic-assisted vaginal hysterectomy and minilaparotomy hysterectomy. MEASUREMENTS AND MAIN RESULTS: Forty patients were randomized to LAVH and 41 to minilaparotomy. Characteristics of patients and indications for surgery in the 2 arms were comparable. In the minilaparotomy group, complications were as follows: 1 case (2.4%) of delayed laparotomy with 2 units of red blood cell transfusion, 2 cases (4.8%) of wound infection, and 3 cases (7.3%) of fever of unknown origin. No minor or major complications were observed in the LAVH group. Postoperative visual analog scale pain scores at days 1 and 2 were significantly lower in the LAVH group (p <.05). The complication rate between the 2 groups was significantly lower for LAVH (p = .026). CONCLUSION: Because LAVH was associated with significantly lower early postoperative pain scores and complication rates, in general LAVH should be preferred to minilaparotomy hysterectomy when the vaginal approach cannot be used. PMID- 17848324 TI - Mid-term outcome of magnetic resonance-guided focused ultrasound surgery for uterine myomas: from six to twelve months after volume reduction. AB - STUDY OBJECTIVE: To clarify the volume change ratio of uterine myomas treated with magnetic resonance-guided focused ultrasound surgery (MRgFUS), in relation to the signal intensity of T(2)-weighted magnetic resonance (MR) images. DESIGN: Prospective study (Canadian Task Force classification II-3). SETTING: Department of Gynecology, Shinsuma General Hospital, Kobe, Japan. PATIENTS: Forty-eight myomas in 35 patients were followed up with MR images 6 months after MRgFUS, and 23 myomas in 17 patients were followed up 12 months after MRgFUS. Before treatment, the myomas were classified into 3 types on the basis of the signal intensity of T(2)-weighted MR images as follows: Type 1, low intensity; type 2, intermediate intensity; type 3, high intensity. INTERVENTIONS: Thermal ablation therapy was performed with an MRgFUS system (ExAblate 2000). MEASUREMENTS AND MAIN RESULTS: MRgFUS produced a greater volume reduction in type 1 and type 2 myomas than in type 3 myomas. Nonperfused areas always diminished in the period after MRgFUS; however, the volume change was affected by the volume change ratio of perfused areas inside the treated myomas. CONCLUSION: At present, type 3 myomas should be exempted from the application of MRgFUS, because the nonperfused ratio immediately after the procedure was small compared with that in type 1 and type 2 myomas, and the subsequent volume change was unfavorable. PMID- 17848325 TI - Small-diameter hysteroscopy with Versapoint versus resectoscopy with a unipolar knife for the treatment of septate uterus: a prospective randomized study. AB - STUDY OBJECTIVE: To compare 2 procedures for metroplasty: resectoscopy with monopolar knife versus small-diameter hysteroscopy fitted with a Versapoint device. DESIGN: Prospective randomized study (Canadian Task Force classification I). SETTING: Endoscopic gynecology units at tertiary care university hospitals. PATIENTS: One hundred-sixty patients with septate uterus and a history of recurrent abortion or primary infertility undergoing hysteroscopic metroplasty from 2001 to 2005. INTERVENTIONS: Hysteroscopic resection of the uterine septum performed with either a 26F resectoscope with unipolar knife (80 women, group A) or a 5-mm diameter hysteroscope with Versapoint device (80 women, group B). All patients were managed expectantly, with follow-up lasting 1 year. MEASUREMENTS AND MAIN RESULTS: Operative parameters (operative time, fluid absorption, complications, need for second intervention) and reproductive outcome parameters (pregnancy, abortion, term and preterm delivery, modality of delivery, cervical cerclage) were measured. Operative time and fluid absorption were significantly greater in group A than in group B (23.4 +/- 5.7 vs 16.9 +/- 4.7 minutes and 486.4 +/- 170.0 vs 222.1 +/- 104.9 mL, respectively). The cumulative complication rate was significantly lower in group B than in group A. No difference in any of the reproductive parameters was observed between the 2 groups: pregnancy and delivery rates were 70% and 81.6% in group A vs 76.9% and 84% in group B. Nine women (18.4%) from group B and 8 women (16%) from group B experienced spontaneous abortions. Most patients (54/82) delivered by cesarean section without differences according to the hysteroscopic technique used for metroplasty (65% in group A vs 67.7% in group B) or to the gestational age (65.1% of term and 68.7% of preterm deliveries). CONCLUSIONS: Small-diameter hysteroscopy with bipolar electrode for the incision of uterine septum is as effective as resectoscopy with unipolar electrode regarding reproductive outcome and is associated with shorter operating time and lower complication rate. PMID- 17848326 TI - Relationship between site and size of bladder endometriotic nodules and severity of dysuria. AB - STUDY OBJECTIVE: The purpose of this study was to evaluate the relationship between frequency/severity of dysuria with anatomic location and diameter of bladder endometriotic lesions. DESIGN: Retrospective analysis (Canadian Task Force classification II-3). SETTING: Tertiary care university hospital. PATIENTS: Forty-one patients with bladder endometriosis (endometrial glands and stroma microscopically diagnosed to infiltrate the muscularis propria). INTERVENTIONS: Laparoscopic partial cystectomy, preoperative scoring of dysuria using 10-point verbal analog scale (VAS). MEASUREMENTS AND MAIN RESULTS: Records of all patients with bladder endometriosis were assessed for frequency/severity of preoperative dysuria, anatomic location (base or dome), and diameter of bladder endometriotic nodule. Basal bladder lesions were observed in 18 (43.9%) of 41 patients versus 23 (56.1%) of 41 in the dome. Of the patients with basal lesions, 14 (77.8%) of 18 had preoperative dysuria versus 8 (34.8%) of 23 with dome lesions. Mean VAS score was 8.5 +/- 2.37 and 5.75 +/- 1.91 for base and dome lesions, respectively. Preoperative dysuria was found in 22 (53.7%) of 41 patients. Mean lesion diameter in patients with dysuria was 25.0 +/- 12.6 mm versus 16.3 +/- 6.8 mm in patients without dysuria. CONCLUSION: Frequency and severity of preoperative dysuria were significantly higher in patients with basal endometriotic nodules. There was a positive correlation between severity of dysuria and lesion diameter. PMID- 17848327 TI - Phase I/II prospective trial of autologous platelet tissue graft in gynecologic surgery. AB - STUDY OBJECTIVE: To perform the original phase I/II trial of autologous platelet tissue graft in gynecologic surgery to evaluate toxicity and efficacy on decreasing pain. DESIGN: Prospective nonrandomized trial (Canadian Task Force classification II-A). SETTING: Teaching hospital. PATIENTS: Fifty-five consecutive patients undergoing major gynecologic surgery were entered into this prospective phase I/II trial and were matched with 55 patients from the previous 6 months. INTERVENTION: After anesthesia was induced, peripheral venous blood (55 mL) was obtained from the patient producing, autologous platelet tissue graft (20 mL). At completion of surgery, autologous platelet tissue graft was directly applied to the surgical site. MEASUREMENTS AND MAIN RESULTS: Median pain on the day of surgery was 2.7 (mild) in the autologous platelet tissue graft group vs 6.7 (severe) in the control group, p <.001. Likewise, pain on postoperative day 1 was 2.1 (mild) in the autologous platelet tissue graft group vs 5.5 (moderate) in the control group, p < or =.001. Median of morphine per hospital stay for the autologous platelet tissue graft group was 17 mg (range 1-98 mg) vs 26 mg (range 3-90 mg) in the control group, which was statistically significant at p = .02. There were no adverse effects associated with autologous platelet tissue graft. CONCLUSIONS: In the original phase I/II prospective trial of autologous platelet tissue graft in gynecologic surgery, there were no apparent adverse effects, and pain was significantly reduced. PMID- 17848328 TI - Modified virtual colonoscopy: a noninvasive technique for the diagnosis of rectovaginal septum and deep infiltrating pelvic endometriosis. AB - In this study, we modified the standard virtual colonoscopy technique to diagnose deep infiltrating pelvic endometriosis. The following modifications were used: (1) insertion of a large obstetric tampon high into the vagina; (2) insertion of a Foley catheter into the rectum and insufflation with CO(2); and (3) scanning only the pelvis. We used a Toshiba Aquillion 64-multidetector computed tomography scanner coupled to a 3-D workstation. By employing various reconstruction modules such as endo-luminal fly-through, cubed volume, 2-D multiplanar reconstruction, 3 D transparent view, and 3-D volume-rendered and maximum intensity projection, we were able to demonstrate deep infiltrating pelvic endometriosis in bowel, urinary tract, and rectovaginal and retroperitoneal spaces. PMID- 17848329 TI - Management of large cystic adnexal tumor by gasless laparoscopic-assisted surgery with wound retractor. AB - We used a retrospective analysis to evaluate the efficacy of a wound retractor used in gasless laparoscopic-assisted surgery by the subcutaneous abdominal wall lift method for the management of large cystic adnexal tumors. In the department of gynecology at a general hospital, 39 patients with large cystic adnexal tumors with an excised tissue weight including cystic contents exceeding 1000 g were treated by gasless laparoscopic-assisted surgery with a wound retractor from January 2001 through December 2006. Intervention was with a gasless laparoscopic assisted adnexal surgery with a wound retractor. The median age of the patients was 51.5 years (range 16-79 years). The median weight of the excised tissue including cystic contents was 1857 g (range 1044-9454 g). The median blood loss was 30 mL (range 10-570 mL). The median surgical duration was 62 minutes (range 26-107 minutes). There were no major surgical complications. Histopathologic diagnosis of the excised tumor was mucinous cystadenoma, 18 cases; serous cystadenoma, 8 cases; mucinous cystadenocarcinoma of low-grade malignancy, 5 cases; dermoid cyst, 4 cases; paraovarian cyst, 2 cases; endometriotic cyst, 1 case; and clear cell adenocarcinoma, 1 case. Bilateral adnexal tumors were noted in 3 cases. We determined that gasless laparoscopic-assisted adnexal surgery with a wound retractor is an effective, minimally invasive procedure to treat large cystic adnexal tumors. PMID- 17848330 TI - When virginity does matter: rigid hysteroscopy for diagnostic and operative vaginoscopy--a series of 26 cases. AB - Virginity in adult women, although a personal decision, is a limiting factor for gynecologists in diagnosis and treatment. This report presents 26 cases of virgin patients with various gynecologic problems: 11 with vaginal bleeding, 7 with heavy discharge and foul odor, 6 with protruding vaginal mass, and 2 with a sensation of vaginal pressure and pain. A rigid hysteroscopy setting was used for diagnostic and operative vaginoscopy. Eleven foreign bodies were removed, mostly clothing fibers and a piece of plastic. In 5 cases, cervical polyps and a subserous myoma were resected and cut into pieces for removal through the hymenal opening. In conclusion, the use of a rigid hysteroscope as a vaginoscope to replace the speculum in adult virgin patients is feasible and introduces an operative option as well. PMID- 17848331 TI - Laparoscopic management of benign serous neoplasia arising from persistent ovarian remnant. AB - Serous cystadenoma arising from ovarian remnant has not been reported in the literature. We report 3 cases with ovarian remnant syndrome that were treated with laparoscopic excision and were proven to be benign serous neoplasia with ovarian origin on final pathologic examination. We review the current evidence for malignant transformation potential of ovarian serous cystadenoma and discuss laparoscopic techniques for management of ovarian remnant syndrome. PMID- 17848332 TI - Thigh abscess mistaken for sarcoma following transobturator tape: a case report and literature review. AB - A 44-year-old female, 1 year status-post ObTape transobturator mid-urethral sling, was evaluated by orthopaedic oncology and urology for persistent thigh pain and a left thigh mass. Multiple muscle biopsies were inconclusive, raising concern for inflammatory sarcoma. After serial debridements of the thigh abscess, sling material was found in the obturator space, which gave the diagnosis. Health care providers, both gynecologic and nongynecologic, need to be aware of serious complications of transobturator slings that may present in atypical ways. PMID- 17848333 TI - Infarcted ectopic spleen presenting as retroperitoneal mass. AB - Wandering or ectopic spleen is an exceptionally rare condition. Because of the abnormally long pedicle, an ectopic spleen is prone to torsion and infarction. Patients can present with abdominal pain or an acute abdomen. The incidence is over a wide age range, but it occurs with a female predominance in the third to fifth decades. We present a case in a 26-year-old female of an infarcted ectopic spleen, initially thought to be a retroperitoneal mass on computed tomography scan, but found at surgery in the lower abdomen. The minimally invasive gynecologic surgeon needs to be aware of this entity, which may rarely be encountered. PMID- 17848335 TI - Laparoscopic positioning and nerve injuries. PMID- 17848336 TI - Laparoscopic hysterectomy. PMID- 17848337 TI - OTC product: Fertell. PMID- 17848339 TI - APhA2007 House of Delegates: improving practice today, preparing for and protecting the profession's future. PMID- 17848340 TI - Career pathways for pharmacists. PMID- 17848341 TI - APhA federal pharmacy initiatives: supporting those in harm's way. PMID- 17848342 TI - A frontline pharmacist's vision: 'practice pharmacy each and every day as if it were your last.'. PMID- 17848343 TI - A noble calling: all of us work toward one goal: serving patients and improving health outcomes. PMID- 17848344 TI - Real leaders wear running shoes: myriad variables need to be evaluated and strategies developed for lifelong career in pharmacy. PMID- 17848345 TI - Report of the 2007 APhA House of Delegates: actions of the official legislative body of the American Pharmacists Association. PMID- 17848347 TI - 2006 APhA treasurer's report. PMID- 17848348 TI - Constructs underlying community pharmacy dispensing functions relative to Florida pharmacy technicians. AB - OBJECTIVES: To assess pharmacist and pharmacy technician opinions on functions community pharmacy technicians should perform. DESIGN: Cross-sectional and descriptive. SETTING: Florida community pharmacies during August and September 2004. PARTICIPANTS: Random sample of Florida community pharmacists (n = 2,000) and Certified Pharmacy Technicians (n = 2,000). INTERVENTION: Self-administered mail questionnaire. MAIN OUTCOME MEASURES: Participant attitudes (6-point Likert type scale: 1, strongly disagree; 6, strongly agree) regarding whether pharmacy technicians should perform 26 community pharmacy dispensing functions. Chi-square difference tests and separate group exploratory factor analyses (EFAs) were conducted. RESULTS: Pharmacists (n = 383) and technicians (n = 579) agreed that technicians should perform 17 of the 26 (65%) functions. The groups differed significantly on eight items that were focused on patient care and beyond technicians' traditional involvement in processing prescriptions, with technicians having a more expansive view of their roles than did pharmacist respondents. Three similar factors were extracted in both groups from the EFAs: functions typical of pharmacy technicians in current practice, clinical pharmacy knowledge functions, and pharmacist-only functions as specified by law. Additionally, general drug knowledge (technician data only) and pharmacy information evaluation and management skills (pharmacist data only) factors were generated. CONCLUSION: Generally, pharmacists and technicians agreed on basic functions involving prescription and claims processing; however, technicians, as compared with pharmacists, supported a more expanded patient care role for themselves. PMID- 17848349 TI - Effect of strategic planning education on attitudes and perceptions of independent community pharmacy owners/managers. AB - OBJECTIVE: To assess the impact of formal education program participation on the attitudes and perceptions of independent community pharmacy owners/managers toward strategic planning. DESIGN: Cross-sectional study. SETTING: United States; June 4-July 30, 2004. PARTICIPANTS: Nationwide random sample of 1,250 owners/managers of independent community pharmacies. INTERVENTION: Mailed survey. MAIN OUTCOME MEASURES: Strategic planning formal education program participation. Comprehensiveness of strategic planning. Attitudes and perceptions of owners/managers of independent community pharmacies toward strategic planning. RESULTS: A total of 527 (42.1%) usable questionnaires were returned. Only 124 (23.5%) respondents indicated that they participated in a formal strategic planning education program. However, of the 141 (26.85%) respondents who indicated that they had conducted strategic planning for their community pharmacy, 111 (89.5%) had participated in a formal strategic planning education program. A significant association was detected between formal education program participation and the conducting of strategic planning (P< or =0.0001). Significant differences were observed for all attitudes and perceptions of independent community pharmacy owners/managers toward strategic planning based on program participation (P< or =0.0001). Finally, respondents who indicated that they had participated in a formal education program had a significantly higher comprehensiveness of strategic planning rating than those respondents who did not participate in an educational program (P< or =0.0001). CONCLUSION: A significant association exists between formal strategic planning education program participation and the conducting of strategic planning by owner/managers of independent community pharmacies, and those participating in such programs have significantly different attitudes and perceptions toward the conducting of strategic planning and have a significantly higher comprehensiveness of strategic planning rating. PMID- 17848350 TI - Designing pharmacy services based on grocery store patron preferences. AB - OBJECTIVE: To assess preferences of grocery store patrons concerning pharmacy services and identify study participant characteristics that may predict the success of pharmacy services in the community setting. DESIGN: Self-administered survey. SETTING: Central Ohio from December 16, 2005, to January 12, 2006. PARTICIPANTS: 163 grocery store patrons. INTERVENTIONS: Eight grocery store survey events. MAIN OUTCOME MEASURES: Responses to survey items about (1) perceived importance of 28 pharmacy services, (2) identification of the 3 most important services, (3) frequency of grocery store and pharmacy use, (4) preferred methods of advertising pharmacy services, and (5) socioeconomic demographics. Preferred services delineated by various demographics also were analyzed. RESULTS: A total of 163 surveys were returned from study participants. Nine services appeared in both the top 12 overall preferred services and the 12 highest-ranked services. Statistically significant differences were observed among services ranked as important or very important by age, race, employment, income, caregiver status, and prescription drug coverage status. The three advertising tools selected most frequently included: weekly grocery store ads (68.6%), in-store signs (51.0%), and flyers attached to prescription bags (36.0%). CONCLUSION: Grocery store patrons would like a wide range of nontraditional pharmacy services that could be implemented into community pharmacies. Pharmacies in grocery stores need to provide both traditional and expanded pharmacy services to meet the desires and expectations of current and potential patients, and expanded marketing methods should be considered. PMID- 17848351 TI - Discordance between ambulatory care clinic and community pharmacy medication databases for HIV-positive patients. PMID- 17848352 TI - Treatment of yellow scorpion (Leiurus quinquestriatus) sting: a case report. AB - OBJECTIVES: To report the treatment given to a 26-year-old Air Force medic who was stung twice by a yellow scorpion (Leiurus quinquestriatus) while stationed in Iraq and to describe the problems and issues related to the use of the scorpion antivenin. PATIENT CASE: The patient presented 2 hours after envenomation to the local military treatment facility, where she was minimally symptomatic initially. Shortness of breath and anxiety developed, and the patient was sedated, intubated, and evacuated to a large Air Force medical facility for more advanced care. Vasopressor support was required during flight. At the medical facility, antivenin was administered, and the patient's cardiac condition was stabilized with norepinephrine drip, mild hydration, and vasopressor support. A second dose of antivenin diluted in sodium chloride and further pressor support were required. ST-segment depression eventually resolved, and the patient was gradually taken off norepinephrine and extubated. She recovered fully within 2 weeks and returned to active duty. DISCUSSION: Because the antivenin used is not licensed by the Food and Drug Administration, informed consent was needed; however, it could not be obtained because the patient was unconscious, intubated, and in a life-or-death situation. Antivenin selection is based on the species of scorpion and symptom severity; therefore, the scorpion should be, with great care, killed for identification. In the military setting, inventory control, storage, and accountability are vital issues surrounding antivenin use, and these are discussed in this article. CONCLUSION: Immediate action and effective communication, along with timely antivenin administration and well-equipped intensive care facilities, were integral in saving the life of this victim of a yellow scorpion envenomation. All level 3 facilities in Southwest Asia must be familiar with ordering, administering, and documenting this antivenin because it is difficult to obtain and infrequently available. PMID- 17848355 TI - Frederick John Wulling 1866-1947: fighter for increased professional educational standards. PMID- 17848353 TI - Medication therapy management: its relationship to patient counseling, disease management, and pharmaceutical care. AB - OBJECTIVE: To delineate the relationship, including similarities and differences, between medication therapy management (MTM) and contemporary pharmacist-provided services, including patient counseling, disease management, and pharmaceutical care, to facilitate the continued evolution of commonly used language and a standard of practice across geographic areas and practice environments. SUMMARY: Incorporation of MTM services into the array of Medicare-funded services affords an opportunity for pharmacists to develop direct patient care services in the community. Defining the role of MTM within the scope of pharmacist-provided patient care activities, including patient counseling, disease management, and all currently provided pharmacy services is essential to the delineation of a viable and sustainable practice model for pharmacists. The definitions of each of these services are offered, as well as comparisons and contrasts of the individual services. In addition to Medicare-eligible patients, MTM services are appropriate for anyone with medication-related needs. MTM is offered as an all encompassing model that incorporates the philosophy of pharmaceutical care, techniques of patient counseling, and disease management in an environment that facilitates the direct collaboration of patients, pharmacists, and other health professionals. CONCLUSION: Defining the role of MTM within the current patient care models, including patient counseling, disease management, and all who provide pharmacy services, is essential in delineating a viable and sustainable practice model for pharmacists. PMID- 17848356 TI - Annual influenza immunization: as important as control of blood pressure and cholesterol as secondary prevention for cardiovascular disease. PMID- 17848357 TI - New drugs: ambrisentan, temsirolimus, and eculizumab. PMID- 17848358 TI - OTC product: Anthelios SX. PMID- 17848359 TI - Monogamy on the fast track. AB - Social monogamy has evolved multiple times and is particularly common in birds. It is not well understood why some of these species are continuously and permanently paired while others occasionally 'divorce' (switch partners). Although several hypotheses have been considered, experimental tests are uncommon. Estrildid finches are thought to be permanently paired because being short-lived opportunistic breeders, they cannot afford the time to form a new pair relationship. Here it is shown through a controlled experimental manipulation that zebra finches (Taeniopygia guttata) allowed to remain with their partners to breed again are faster to initiate a clutch (by approx. 3 days) than birds separated from their mates that have to re-pair, supporting the hypothesis that continuous pairing speeds up initiation of reproduction, a benefit of long-term monogamy in a small, short-lived, gregarious species. PMID- 17848360 TI - Age-related shapes of the cost of reproduction in vertebrates. AB - The shape of the association between age and the cost of reproduction varies across species. However, it is unclear whether there are any general patterns in the way the cost of reproduction varies with life history, taxon or ecological function. Using a simple theoretical method, we identified three characteristic patterns to describe the age-related survival cost of reproduction. The most frequent pattern is an approximately exponential decay (ED) with increasing age. Two additional u-shaped patterns were identified, where the cost of reproduction was higher for young and old individuals compared with intermediate-aged individuals. The majority of these u-shaped curves suggested higher costs of reproduction at older ages (RQ), with the rest suggesting a higher cost at young ages (LQ). While predators were most likely to exhibit ED-shaped cost curves, herbivores were equally likely to exhibit ED and RQ curves; birds were likely to exhibit ED-shaped curves and mammals were split equally between ED and RQ curves. These findings suggest that there may be predictable differences in the age related shape of the cost of reproduction between species, but further research is required to identify the mechanisms generating such differences. PMID- 17848361 TI - Miocene whale-fall from California demonstrates that cetacean size did not determine the evolution of modern whale-fall communities. AB - Whale-fall communities support a deep-sea invertebrate assemblage that subsists entirely on the decaying carcasses of large cetaceans. The oldest whale-falls are Late Eocene in age, but these early whale-falls differ in faunal content and host cetacean size from Neogene and Recent whale-falls. Vesicomyid bivalves, for example, are major components of the sulphophilic stage in Miocene and Recent whale-fall communities, but they are absent from Palaeogene fossil whale-falls. The differences between Palaeogene and Neogene communities led to the hypothesis that the origin of modern whale-fall communities was linked with the evolution of extremely large mysticetes, which provided sufficient biomass and oil to sustain the modern complement of whale-fall invertebrates. Here, we describe a fossil whale-fall community from the Miocene of California, showing vesicomyid bivalves in direct association with a host mysticete smaller than the adult individuals of any living mysticete species. This association, which is the youngest yet reported from the Neogene of North America, demonstrates that body size is not a necessary factor for the formation of modern whale-fall communities. Instead, we suggest that high skeletal oil content may have been a more important factor, which, based on the age of the fossil whale-fall, evolved at least by the Late Miocene. PMID- 17848362 TI - Entrapment of water by subunit c of ATP synthase. AB - We consider an ancient protein, and water as a smooth surface, and show that the interaction of the two allows the protein to change its hydrogen bonding to encapsulate the water. This property could have made a three-dimensional microenvironment, 3-4 Gyr ago, for the evolution of subsequent complex water based chemistry. Proteolipid, subunit c of ATP synthase, when presented with a water surface, changes its hydrogen bonding from an alpha-helix to beta-sheet like configuration and moves away from its previous association with lipid to interact with water surface molecules. Protein sheets with an intra-sheet backbone spacing of 3.7A and inter-sheet spacing of 6.0 A hydrogen bond into long ribbons or continuous surfaces to completely encapsulate a water droplet. The resulting morphology is a spherical vesicle or a hexagonal crystal of water ice, encased by a skin of subunit c. Electron diffraction shows the crystals to be highly ordered and compressed and the protein skin to resemble beta-sheets. The protein skin can retain the entrapped water over a temperature rise from 123 to 223 K at 1 x 10(-4) Pa, whereas free water starts to sublime significantly at 153 K. PMID- 17848363 TI - A beetle-inspired solution for underwater adhesion. AB - Glue-free reversible adhesion was achieved underwater using a beetle-inspired mushroom-shaped fibrillar microstructure. Structured surfaces reveal a 25% increase in pull-off force when immersed in water and their underwater attachment is 20 times more effective than that of flat surfaces. The van der Waals interaction that underlies the adhesion of the mushroom-shaped fibrillar microstructure is significantly enhanced by a suction effect when underwater. This results in a higher adhesive capability of the material, with potential in medicine, bio- and marine technologies and a range of applications in liquid dominated environments. PMID- 17848364 TI - Premature deactivation of soleus during the propulsive phase of cat jumping. AB - It has been shown that cat soleus (SOL) forces remain nearly constant despite increases in electromyography (EMG) activity for increasing speeds of locomotion, while medial gastrocnemius (MG) forces and EMG activity increase in parallel. Furthermore, during jumping, average cat SOL forces decrease, while average EMG activity increases dramatically compared with walking conditions. Finally, during rapid paw-shake movements, SOL forces and EMG activities are nearly zero. Based on these results, we hypothesized that the SOL is deactivated, despite ankle extensor requirements, if the contractile conditions limit SOL force potential severely. The purposes of this study were to (i) investigate SOL EMG activity and force as a function of its contractile conditions during jumping, (ii) test whether SOL EMG activity is associated with SOL contractile conditions, and (iii) determine the functional implications of SOL EMG activity during jumping. It was found that the SOL was prematurely deactivated in two distinct phases during the propulsive phase of jumping, in which shortening speeds approached or even exceeded the maximal speed of muscle shortening. We concluded that the SOL was prematurely deactivated to save energy because its mechanical work output approached zero, and speculated that the first phase of deactivation might be caused by a decrease in group Ia firing associated with active shortening and the second by a pre-programmed response inherent to the central pattern generator. PMID- 17848365 TI - Bats respond to polarity of a magnetic field. AB - Bats have been shown to use information from the Earth's magnetic field during orientation. However, the mechanism underlying this ability remains unknown. In this study we investigated whether bats possess a polarity- or inclination-based compass that could be used in orientation. We monitored the hanging position of adult Nyctalus plancyi in the laboratory in the presence of an induced magnetic field of twice Earth-strength. When under the influence of a normally aligned induced field the bats showed a significant preference for hanging at the northern end of their roosting basket. When the vertical component of the field was reversed, the bats remained at the northern end of the basket. However, when the horizontal component of the field was reversed, the bats changed their positions and hung at the southern end of the basket. Based on these results, we conclude that N. plancyi, unlike all other non-mammalian vertebrates tested to date, uses a polarity-based compass during orientation in the roost, and that the same compass is also likely to underlie bats' long-distance navigation abilities. PMID- 17848366 TI - The fiddler crab Uca mjoebergi uses colour vision in mate choice. AB - Although the role of colour in mate choice is well known, few tests of colour vision have been based on mating behaviour. Females of the fiddler crab Uca mjoebergi have recently been shown to use claw coloration to recognize conspecific males. In this study I demonstrate that the females use colour vision for this task; preferentially approaching yellow claws over grey claws regardless of their intensity while failing to discriminate between yellow claws differing in intensity. This is one of only a handful of studies confirming the involvement of colour vision in mate choice and the first conclusive evidence in fiddler crabs. PMID- 17848367 TI - Q-cgi: new techniques to assess variation in perception applied to facial attractiveness. AB - We present novel methods for assessing variation in the perception of subjective cues based on a fusion of Q-methodology with computer graphics techniques. Participants first Q-sort face stimuli based upon a subjective quality; a randomization-based statistic is then calculated to test whether groups of participants differ in their perception. Computer graphics are then used to extract and illustrate the differences in the manner which participants sorted so that the differences can be quantified. As a demonstration, the technique is applied to investigate the effects of prospective relationship duration and of sexual restrictiveness on the characteristics which participants find attractive in photographs of opposite-sex faces. Results show that in a naturally varying set of faces, female participants prefer facial cues related to masculinity for short-term relationships, whereas characteristics related to positive personality attributes are preferred for long-term relationships. For short-term relationships, male participants appear to prefer more feminine, youthful faces. Preferences of individuals with less restricted sexual strategy paralleled short term preferences in that more feminine female faces and more masculine male faces were preferred. PMID- 17848368 TI - Prehistoric inter-archipelago trading of Polynesian tree snails leaves a conservation legacy. AB - Inter-archipelago exchange networks were an important aspect of prehistoric Polynesian societies. We report here a novel genetic characterization of a prehistoric exchange network involving an endemic Pacific island tree snail, Partula hyalina. It occurs in the Society (Tahiti only), Austral and Southern Cook Islands. Our genetic data, based on museum, captive and wild-caught samples, establish Tahiti as the source island. The source lineage is polymorphic in shell coloration and contains a second nominal species, the dark-shelled Partula clara, in addition to the white-shelled P. hyalina. Prehistoric inter-island introductions were non-random: they involved white-shelled snails only and were exclusively inter-archipelago in scope. Partulid shells were commonly used in regional Polynesian jewellery, and we propose that the white-shelled P. hyalina, originally restricted to Tahiti, had aesthetic value throughout these archipelagoes. Demand within the Society Islands could be best met by trading dead shells, but a low rate of inter-archipelago exchange may have prompted the establishment of multiple founder populations in the Australs and Southern Cooks. The alien carnivorous land snail Euglandina rosea has recently devastated populations of all 61 endemic species of Society Island partulid snails. Southern Cooks and Australs P. hyalina now represent the only unscathed wild populations remaining of this once spectacular land snail radiation. PMID- 17848369 TI - Enfleurage, lipid recycling and the origin of perfume collection in orchid bees. AB - Enfleurage, the extraction of elusive floral scents with the help of a lipophilic carrier (grease), is widely used in the perfume industry. Male neotropical orchid bees (Euglossini), which accumulate exogenous fragrances as pheromone analogues, use a similar technique. To collect fragrances, the bees apply large amounts of straight-chain lipids to odoriferous surfaces from their cephalic labial glands, which dissolve the volatiles, and the mixture is then transferred to voluminous hind-leg pockets. Here, we show that males do in fact operate a lipid conveyor belt to accumulate and concentrate their perfume. From the hind-leg pockets of caged male Euglossa viridissima, deuterated derivatives of carrier lipids were consecutively sequestered, shuttled back to the labial glands and reused on consecutive bouts of fragrance collection. Such lipid cycling is instrumental in creating complex perfume bouquets. Furthermore, we found that labial glands of male orchid bees are strikingly similar to those of scent-marking male bumblebees in terms of size, form and structure. This, and a prominent overlap in secretory products, led us to propose that perfume collection evolved from scent-marking in ancestral corbiculate bees. PMID- 17848370 TI - A mixed-age classed 'pelycosaur' aggregation from South Africa: earliest evidence of parental care in amniotes? AB - Living species of mammals, crocodiles and most species of birds exhibit parental care, but evidence of this behaviour is extremely rare in the fossil record. Here, we present a new specimen of varanopid 'pelycosaur' from the Middle Permian of South Africa. The specimen is an aggregation, consisting of five articulated individuals preserved in undisturbed, close, lifelike, dorsal-up, subparallel positions, indicating burial in 'life position'. Two size classes are represented. One is 50% larger than the others, is well ossified, has fused neurocentral sutures and is distinguished by a coat of dermal ossifications that covers the neck and shoulder regions. We regard this individual to be an adult. The remaining four skeletons are considered to be juveniles as they are approximately the same size, are poorly ossified, have open neurocentral sutures and lack dermal ossifications. Aggregates of juvenile amniotes are usually siblings. Extant analogues of adult and juvenile groupings suggest that the adult is one of the parents, leading us to regard the aggregation as a family group. The Late Middle Permian age of the varanopid family predates the previously known oldest fossil evidence of parental care in terrestrial vertebrates by 140 Myr. PMID- 17848371 TI - The effect of energy reserves and food availability on optimal immune defence. AB - In order to avoid both starvation and disease, animals must allocate resources between energy reserves and immune defence. We investigate the optimal allocation. We find that animals with low reserves choose to allocate less to defence than animals with higher reserves because when reserves are low it is more important to increase reserves to reduce the risk of starvation in the future. In general, investment in immune defence increases monotonically with energy reserves. An exception is when the animal can reduce its probability of death from disease by reducing its foraging rate. In this case, allocation to immune defence can peak at intermediate reserves. When food changes over time, the optimal response depends on the frequency of changes. If the environment is relatively stable, animals forage most intensively when the food is scarce and invest more in immune defence when the food is abundant than when it is scarce. If the environment changes quickly, animals forage at low intensity when the food is scarce, but at high intensity when the food is abundant. As the rate of environmental change increases, immune defence becomes less dependent on food availability. We show that the strength of selection on reserve-dependent immune defence depends on how foraging intensity and immune defence determine the probability of death from disease. PMID- 17848372 TI - Resolving a zoological mystery: the kouprey is a real species. AB - The kouprey is a rare and enigmatic forest ox discovered by scientists in Cambodia only in 1937. Numerous morphological hypotheses have been proposed for the origin of the kouprey: that it is a species closely related to banteng and gaur, two other wild oxen of southeast Asia; a morphologically divergent species placed in a separate genus, named Novibos; a wild species linked to aurochs and domestic cattle; a vicariant population of banteng; a feral cattle; or a hybrid of banteng with either zebu cattle, gaur or water buffalo. In a recent paper, which gained a lot of media coverage, Galbreath et al. analysed mitochondrial DNA sequences and concluded that the kouprey never existed as a wild, natural species, and that it was a feral hybrid between banteng and zebu cattle. Here we analyse eight DNA markers-three mitochondrial regions and five nuclear fragments representing an alignment of 4582 nucleotides for the holotype of the kouprey and all related species. Our results demonstrate that the kouprey is a real and naturally occurring species, and show that Cambodian populations of banteng acquired a mitochondrial genome of kouprey by natural introgressive hybridization during the Pleistocene epoch. PMID- 17848374 TI - Lysostaphin as a treatment for systemic Staphylococcus aureus infection in a mouse model. AB - OBJECTIVES: With the isolation of clinical strains of Staphylococcus aureus carrying the gene that confers vancomycin resistance, the need for novel antistaphylococcals has become more urgent. Lysostaphin, an example of such a novel therapeutic, is an endopeptidase that rapidly lyses S. aureus through proteolysis of the staphylococcal cell wall. We evaluated its efficacy as a therapeutic agent for treatment of systemic S. aureus infection in a mouse model. METHODS: Mice (5-10 per group) challenged with methicillin-susceptible S. aureus developed bacteraemia and organ infections while mice challenged with methicillin resistant S. aureus (MRSA) developed organ infections. The challenged mice received various intravenous doses of recombinant lysostaphin, administered once a day for 1-3 days when compared with treatment with oxacillin or vancomycin. Some mice also received treatment of lysostaphin combined with oxacillin or vancomycin. Following treatment, bacteraemia was determined, and mice were sacrificed and organ infection was determined. RESULTS AND CONCLUSIONS: Lysostaphin administered at 5 mg/kg once a day for 3 days consistently cleared S. aureus from the blood and the organs of infected mice. Furthermore, the combination of lysostaphin and oxacillin or vancomycin demonstrated increased efficacy against MRSA over lysostaphin alone allowing the therapeutic dose of lysostaphin to be reduced to 1 mg/kg. These results demonstrate that lysostaphin is an effective treatment for eradicating S. aureus from the blood and from the organs of infected mice. PMID- 17848373 TI - Comparison of the effects of macrolides, amoxicillin, ceftriaxone, doxycycline, tobramycin and fluoroquinolones, on the production of pneumolysin by Streptococcus pneumoniae in vitro. AB - OBJECTIVES: To compare the effects of subinhibitory concentrations of amoxicillin, ceftriaxone, azithromycin, clarithromycin, erythromycin, telithromycin, clindamycin, ciprofloxacin, moxifloxacin, tobramycin and doxycycline on pneumolysin production by a macrolide-susceptible strain and two macrolide-resistant strains [erm(B) or mef(A)] of Streptococcus pneumoniae. METHODS: Pneumolysin was assayed using a functional procedure based on the influx of Ca(2+) into human neutrophils. RESULTS: Only the macrolides/macrolide-like agents caused significant attenuation of the production of pneumolysin, which was evident with all three strains of the pneumococcus. CONCLUSIONS: Macrolides, at sub-MICs, but not other classes of antibiotic, subvert the production of pneumolysin, even in the presence of (and irrespective of the mechanism of) macrolide resistance in S. pneumoniae. PMID- 17848375 TI - A systematic review and meta-analysis of the effectiveness and safety of atovaquone proguanil (Malarone) for chemoprophylaxis against malaria. AB - OBJECTIVES: A systematic review and meta-analysis of the effectiveness of atovaquone-proguanil (Malarone) as a chemoprophylactic agent against malaria. METHODS: The data sources searched for this study included Cochrane systematic reviews (on infectious diseases), MEDLINE and EMBASE, Web of Knowledge and Annals of Tropical Medicine. All unconfounded randomized controlled trials assessing the chemoprophylaxis against malaria with atovaquone-proguanil were included in the review. Data on study design, study sample, inclusion and exclusion criteria, allocation, blinding, primary and secondary study end points were all extracted by one reviewer and independently rechecked by the second reviewer. RESULTS: In general, all 10 studies identified had excellent quality with total scores of >or=4 using the Jadad criteria. Ten controlled trials comprising 4,539 participants were included for this review. A meta-analysis of six of the ten studies found chemoprophylaxis with atovaquone-proguanil, with a prophylaxis efficacy of 95.8% (95% CI = 91.5-97.9), to be superior to placebo. It was also considered safe and better tolerated with fewer treatment-related adverse events that could lead to premature discontinuation of prophylaxis than in controls. Comparison with alternative chemoprophylaxis also showed atovaquone-proguanil to be better tolerated with fewer treatment-related self-reported adverse events (RR = 0.8234; 95% CI = 0.673164-1.01) or severe adverse events (RR = 0.6140; 95% CI = 0.420055-0.8975). Atovaquone-proguanil is well tolerated with no difference in non-compliance with placebo (RR = 0.8804; 95% CI = 0.6964-1.113; I(2) = 31.4%). CONCLUSIONS: Evidence from this review shows that atovaquone-proguanil is highly efficacious as a prophylactic agent against malaria infection and is very well tolerated compared with other antimalarial agents. PMID- 17848376 TI - Mortality and delay in effective therapy associated with extended-spectrum beta lactamase production in Enterobacteriaceae bacteraemia: a systematic review and meta-analysis. AB - OBJECTIVES: We performed a systematic review and meta-analysis to examine the impact of extended-spectrum beta-lactamase (ESBL) production on mortality and delay in effective therapy in Enterobacteriaceae bacteraemia. METHODS: We searched the PubMed database using the terms 'bacteremia or bloodstream' and 'ESBL or extended-spectrum beta-lactamase'. Included studies contained numbers of and mortality figures for patients with bacteraemia caused by ESBL producers and non-producers. Data extracted included crude relative risk (RR), adjusted odds ratio and 95% confidence intervals (CIs) for mortality and delayed effective therapy. Results were pooled using a random effects model. RESULTS: Sixteen studies met inclusion criteria. Meta-analysis of crude RRs demonstrated significantly increased mortality in ESBL-associated bacteraemia (pooled RR 1.85, 95% CI 1.39-2.47, P < 0.001). However, only one study reported RR controlled for confounding. Ten studies reported comparative data on delay in effective therapy. Meta-analysis of crude RRs demonstrated significantly increased incidence of delay in effective therapy in ESBL-associated bacteraemia (pooled RR 5.56, 95% CI 2.94-10.51, P < 0.001). CONCLUSIONS: In Enterobacteriaceae bacteraemia, ESBL production is associated with increased mortality and delay in effective therapy. However, lack of controlled studies limits interpretation regarding causality, and further controlled studies are required. PMID- 17848378 TI - Response of CaSO4:Dy based TL dosemeter system to high-energy photon beams: theoretical simulation. AB - Response of thermoluminescence (TL) discs under different filter regions of a CaSO(4):Dy based TL dosemeter system was simulated to high-energy photon beams in the energy range of 1.25 MeV to 24 MV ( approximately 9 MeV). This was done using FLUKA Monte Carlo code and also experimentally verified for some energy points. Response of disc D1 under metal filter combination was found to increase with photon energy, whereas that for the discs under polystyrene filter and open window regions of the dosemeter decreases continuously. The changes in the response of the discs under polystyrene filter and open window were attributed to the lack of build-up material. The increase in the response of disc D1 was due to the contribution from secondary electrons produced through Compton and pair production processes mainly arising out from the metal filter combination. The knowledge of the change in the response of individual discs and the ratio of discs' responses under different filter regions of the dosemeter system could be used for the measurement of energy of bremsstrahlung radiation that exists in and around high-energy electron accelerator and could be used for accurate evaluation of personal dose equivalent in high-energy photon field. PMID- 17848379 TI - The efficiency curve: a new function. AB - Working from first principles, an efficiency curve function has been developed by considering the physics of photon transport through matter. The function has been compared to other function in popular usage and been found to fit the data better especially about the knee of the curve. The main disadvantage of the new function is that it is data hungry, but this can be overcome by use of Monte Carlo simulations. PMID- 17848380 TI - Results of field trials using the NPL simulated reactor neutron field facility. AB - The NPL simulated reactor neutron field facility provides neutron spectra similar to those found in the environs of UK gas-cooled reactors. Neutrons are generated by irradiating a thick lithium-alloy target with monoenergetic protons between 2.5 and 3.5 MeV (depending on the desired spectrum), and then moderated by a 40 cm diameter sphere of heavy water. This represents an extremely soft workplace field, with a mean neutron energy of 25 keV and, more significantly, a mean fluence to ambient dose equivalent conversion coefficient of the order of 20 pSv cm(2), approximately 20 times lower than those of the ISO standard calibration sources (252)Cf and (241)Am-Be. Results of field trials are presented, including readings from neutron spectrometers, personal dosimeters (active and passive) and neutron area survey meters, and issues with beam monitoring are discussed. PMID- 17848381 TI - Analysis of the uncertainty in internal dose estimate resulting from biological stochastic variability of excretion. AB - A method for investigating the uncertainty in internal dose estimate resulting from biological stochastic variability of excretion is proposed in the paper. The method is based on analysing generated cases of individual monitoring data using Monte Carlo simulation technique. In case of a single intake and assumption of stochastic variability of excretion is a single source of uncertainty it was shown that the intake (dose) uncertainty depends exclusively on the uncertainty of the bioassay data and the number of daily urine (faeces) measurements. Assuming a log-normal distribution for describing the variability of excretion a simple expression for calculating the uncertainty was proposed. In case of routine monitoring data it was shown that the uncertainty of annual intake (dose) estimate would depend on biological stochastic variability of excretion, type of excretion function and the number of monitoring intervals in a year. By the example of Pu and U aerosols it was shown that the effects of decreasing uncertainty in the dose estimate resulting from increasing the number of monitoring intervals in a year and from decreasing the uncertainty of bioassay data (performing a number of successive daily measurements, once in a year) should be estimated to optimise the routine monitoring program. PMID- 17848382 TI - Argentine intercomparison programme for personal dosimetry. AB - An Intercomparison Programme is being carried out in Argentina for individual monitoring services. The programme was designed to test, on a voluntary basis, the performance of the laboratories that provide individual monitoring services for X and gamma radiation fields in the range from low-level dose up to 100 mSv. Irradiations were performed in full accordance with ISO 4037-3 recommendations by the Regional Reference Centre for Dosimetry (CRRD), belonging to Atomic Energy Commission (CNEA) and the Physical Dosimetry Laboratory of the Nuclear Regulatory Authority (ARN). At the same time, several items have been asked to each participant pertaining to the action range, the detectors' characteristics, the laboratory procedures, the existence of an algorithm and its use for the dosemeter evaluation. In this study the evolution of the laboratories' performance throughout the programme, based on ISO 14146 acceptance criteria, is shown. PMID- 17848383 TI - European Workshop on Individual Monitoring of Ionising Radiation (IM2005). PMID- 17848384 TI - Dose to persons assisting voluntarily during X-ray examinations of large animals. AB - Pet owners often assist voluntarily while their pets are being X-rayed during a medical examination. Medical staff members occupationally exposed to radiation are monitored regularly, as they wear personal dosemeters, whereas no dose measurements are carried out on voluntarily assisting persons, as measurements are both cost- and time-intensive. However, the dose limits prescribed in the German radiation protection regulations have to be observed for these volunteers as well. To assist the legislator in deciding whether the German regulation should be changed so that in future the dose of voluntarily assisting persons should also be determined-either by wearing a dosemeter or in another way investigations with regard to the radiation dose exposure suffered by volunteers were performed within the scope of a research project. The personal dose equivalent Hp(10) for persons assisting knowingly and willingly in X-ray examinations in veterinary medicine was measured for different examination scenarios. Typical exposure situations have been identified and measurements performed in the field of scattered X-rays. The measurements were carried out on animals in veterinary practices and, to verify these measurements, also under laboratory conditions. This paper deals with X-ray examinations of large animals, with the focus especially on horses. The measured personal dose equivalent values of voluntary helpers in equine radiology are in the order of a few microsieverts. PMID- 17848385 TI - Monte Carlo modelling for in vivo measurements of Americium in a knee voxel phantom: general criteria for an international comparison. AB - The general criteria and the scientific approach adopted for an 'International comparison on Monte Carlo modelling for in vivo measurement of Americium in a knee phantom' that is being organised within the EU Coordination Action CONRAD (Coordinated Network for Radiation Dosimetry) are described her. Detection system and a knee voxel phantom based on a computerised axial tomography of the Spitz anthropometric knee phantom with a homogeneous distribution of 241Am in bone have been considered for the simulation of three specific situations: (a) a single Low Energy Germanium detector for a point 241Am source in air; (b) the calculation of photon fluence spectra in air around the voxel phantom; and (c) the calculation of the energy distribution of pulses and peak detection efficiency in the real detection system geometry. PMID- 17848386 TI - Variations in backscatter observed in PMMA whole-body dosimetry slab phantoms. AB - Polymethyl methacrylate (PMMA) is a useful material for dosimetry phantoms in many ways including approximate tissue equivalence, stability, accessibility and ease of use. However, recent studies indicate that PMMA may have some unanticipated variation in backscatter from one phantom to another. While the reasons behind the variations have not been identified, it has been demonstrated that the backscatter from one phantom to another may vary by as much as 15%, resulting in a dosemeter response variation of as much as 5%. This unexpected contribution to uncertainty in delivered dose to a dosemeter may be quite large compared to the normally estimated uncertainty, potentially causing problems with calibration and performance testing. This paper includes data supporting the differences in backscatter among phantoms, and results from tests on the phantoms performed in an effort to identify possible causes. PMID- 17848387 TI - An approach to reduction of uncertainties in internal doses reconstructed for the Techa River population. AB - A methodology was developed for reduction of uncertainties in estimates of internal dose for residents of the Techa Riverside communities, who were exposed as a result of releases of radionuclides from the Mayak plutonium production facility in 1949-56. The 'Techa River Dosimetry System' (TRDS) was specifically elaborated for reconstruction of doses. A preliminary analysis of uncertainty for doses estimated using the current version of the TRDS showed large ranges in the uncertainty of internal absorbed dose and led to suggestions of methods to reduce uncertainties. The new methodological approaches described in this paper will allow for significant reduction of uncertainties of 90Sr-dose. The major sources of reduction are: making use of individual measured values of 90Sr and through development of a Household Registry to associate unmeasured persons with measured persons living in the same household(s). PMID- 17848388 TI - Natural radioactivity and dose estimation in underground water from the Sudety Mountains in Poland. AB - Studies of natural radioactivity in spring water in Swieradow-Czerniawa Health Resort were performed with the use of nuclear and mass spectrometry techniques. The investigated region is situated in the Sudety Mountains, where uranium exploration was conducted in the early 1950s of the last century. Annual effective doses due to radionuclide intake were calculated for 4 out of 20 spring waters used for consumption by spa patients and inhabitants. The summed effective doses without 222Rn were of the range 0.4 microSv to 9.2 microSv, for patient for of a 20-day duration stay and from 1.3 microSv y(-1) to 26.7 microSv y(-1) for an inhabitant. The contribution of radon consumed with water raises these values to 209.4 microSv per 20 days and 608.3 microSv y(-1) for a patient and inhabitant, respectively. PMID- 17848389 TI - Use of air monitoring and experimental aerosol data for intake assessment for Mayak plutonium workers. AB - One of the major uncertainties in reconstructing doses to Mayak Plutonium (Pu) workers is the unknown exposure patterns experienced by individuals. These uncertainties include the amounts of Pu inhaled, the temporal exposure pattern of Pu air concentration, the particle-size distribution and solubility of the inhaled aerosols. To date, little individual and workplace-specific information has been used to assess these parameters for the Mayak workforce. However, extensive workplace-specific alpha activity air monitoring data set has been collated, which, if coupled with individual occupational histories, can potentially provide customised intake scenarios for individual Mayak workers. The most available Pu air concentration data are annual averages, which exist for over 100 defined work stations at radiochemical and chemical-metallurgical manufacturing facilities and basically for the whole period of Mayak production operations. Much sparser but more accurate data on Pu concentrations in workers' breathing zone are available for some major workplaces and occupations. The latter demonstrate that within a working shift, Pu concentrations varied over a range of several orders of magnitude depending on the nature of the operations performed. An approach to use the collated data set for individual intake reconstruction is formulated and its practical application is demonstrated. Initial results of ongoing experimental study on historic particle size at Mayak PA and their implications for intake estimation are presented. PMID- 17848390 TI - Parent and adolescent distribution of responsibility for diabetes self-care: links to health outcomes. AB - OBJECTIVE: To examine the relation of adolescent and parent responsibility distribution for diabetes self-care to psychological and physical health. METHODS: We interviewed children (mean age 12 years) annually for 3 years and asked parents to complete a questionnaire. Both reported how diabetes self-care was distributed in the family. Amount of responsibility held by the child only, the parent only, and shared between child and parent was calculated. Psychological distress, competence, and diabetes outcomes were assessed at each wave. RESULTS: In both cross-sectional and longitudinal (lagged) analyses, multilevel modeling showed that shared responsibility was consistently associated with better psychological health, good self-care behavior, and good metabolic control, whereas child and parent responsibility were not. In some cases, links of shared responsibility to health outcomes were stronger among older adolescents. CONCLUSIONS: These findings highlight the importance of shared responsibility for diabetes self-care through early to middle adolescence. PMID- 17848391 TI - Review of the literature: integrating psychoneuroimmunology into pediatric chronic illness interventions. AB - OBJECTIVE: Provide an orientation to psychoneuroimmunology, a rationale for including assessments of immune function in intervention studies of pediatric chronic illness, review the current literature, and provide recommendations for future research. METHODS: Using electronic searches and previous reviews, selected and reviewed published studies in which immunological changes related to psychological interventions were assessed in pediatric samples. RESULTS: Eight studies were identified and included in the review. These utilized a range of interventions (e.g., disclosure and hypnosis) and included a variety of pediatric samples (e.g., those with asthma, HIV infection, or lupus). CONCLUSIONS: Results suggest that psychological intervention can influence immune function in pediatric samples. Recommendations for advancing our knowledge by studying populations for whom the immune system plays an active role in disease pathophysiology, measuring disease-relevant immune mediators, studying pediatric patients under times of stress, and focusing on interventions aimed at altering the stress system are provided. PMID- 17848392 TI - Commentary: lessons in pediatric neuropsycho-oncology: what we've learned since Johnny Gunther. PMID- 17848393 TI - The Canadian ACE-inhibitor trial to improve renal outcomes and patient survival in kidney transplantation--study design. AB - BACKGROUND: In non-transplant patients with chronic kidney disease and proteinuria, inhibition of the renin-angiotensin system with an ACE-inhibitor or an angiotensin receptor blocker has been shown to delay the progression of renal disease. Observational studies in the kidney transplant population have produced conflicting results with some studies showing benefit and others no benefit of renin-angiotensin system blockade. METHODS: This report describes the design and methodological issues of a randomized controlled trial evaluating the effect of ramipril in a renal transplant population. This study has been funded by a peer reviewed grant from the Canadian Institutes of Health Research and is registered on the International Standard Randomised Controlled Trial Number Registry (ISRCTN 78129473). RESULTS: The study will randomize 528 kidney transplant patients (11 Canadian centers) with proteinuria and an estimated GFR between 20 and 55 ml/min/1.73 m(2) to either ramipril (5 mg BID) or placebo. Patients, clinical staff and investigators will be blinded to treatment allocation. The primary outcome will be a composite measure incorporating doubling of serum creatinine, end stage renal disease or death. Principal secondary outcomes include: decline in GFR using a radioisotopic method, change in proteinuria, change in blood pressure, incidence of adverse events (e.g. hyperkalemia, anemia), incidence of cardiovascular events and health-related quality of life assessed by the Short Form-36 and the EuroQol-5D. CONCLUSIONS: Upon completion, this trial will provide clinically meaningful evidence about whether treatment with an ACE-inhibitor will reduce patient mortality and prolong allograft survival in renal transplant recipients. PMID- 17848394 TI - Impact of ENPP1 genotype on arterial calcification in patients with end-stage renal failure. AB - BACKGROUND: Ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) generates inorganic pyrophosphate, a solute that serves as an essential physiological inhibitor of calcification. Inactivating mutations of ENPP1 are associated with generalized arterial calcification of infancy. We hypothesized the ENPP1 K121Q variant to be associated with increased vascular calcification in patients with end-stage renal failure. SUBJECTS AND METHODS: We recruited 79 patients with end stage renal failure undergoing dialysis treatment and genotyped them for the ENPP1 K121Q polymorphism. Next, we matched to each patient with ENPP1 121KQ genotype (n=15) a respective control with ENPP1 121KK genotype by gender, age, diabetes and duration of dialysis treatment. The matching ratio was 1:1. Severity of coronary calcification was quantified by computed tomography, and aortic stiffness was measured by pulse-wave analysis. RESULTS: Patients with ENPP1 121KQ genotype had a significantly higher coronary calcium score (1385 vs 94; n=30; P=0.033), and also a higher aortic pulse-wave velocity when compared to matched controls with ENPP1 121KK genotype (13.69 m/s vs 9.37 m/s; P=0.003). CONCLUSIONS: Taken together, our study suggests a potential role of the ENPP1 K121Q polymorphism in arterial calcification of patients with end-stage renal failure. Patients heterozygous for the ENPP1 K121Q polymorphism have higher coronary calcification scores and increased aortic stiffness, and may benefit from more intense treatment in order to prevent progression of arterial calcification. PMID- 17848395 TI - Hypokalaemia and subsequent hyperkalaemia in hospitalized patients. AB - BACKGROUND: The objective was to study the epidemiology of hypokalaemia [serum potassium concentration (S(K)) <3.5 mmol/l] in a general hospital population, specifically focusing on how often and why patients develop subsequent hyperkalaemia (S(K) > or =5.0 mmol/l). METHODS: In a 3-month hospital-wide study we analysed factors contributing to hypokalaemia and subsequent hyperkalaemia. RESULTS: From 1178 patients in whom S(K) was measured, 140 patients (12%) with hypokalaemia were identified (S(K) 3.0 +/- 0.3 mmol/l). One hundred patients (71%) had hospital-acquired hypokalaemia. Common causes of hypokalaemia included gastrointestinal losses (67%), diuretics (36%) and haematological malignancies (9%). In 104 patients (74%), hypokalaemia was multifactorial. Hypokalaemia frequently coexisted with hyponatraemia (24%) and, when measured, hypomagnesaemia (61%). Twenty-three patients (16%) developed hyperkalaemia (highest S(K) 5.7 +/- 0.7 mmol/l) following hypokalaemia. In these patients, potassium suppletion was not more common (70 vs 59%, P = 0.5), but when potassium was given, the total amount administered was significantly higher (median 350 mmol vs 180 mmol, P = 0.02). Furthermore, these patients more often received total parenteral nutrition (17 vs 4%, P = 0.02) and magnesium suppletion (30 vs 9%, P = 0.009), and more often had haematological malignancies (22 vs 6%, P = 0.03). CONCLUSIONS: Hypokalaemia is a multifactorial and usually hospital-acquired condition associated with hyponatraemia and hypomagnesaemia. One out of every six patients with hypokalaemia developed subsequent hyperkalaemia. Besides potassium suppletion, total parenteral nutrition (source of potassium), magnesium suppletion (may reduce kaliuresis) and haematological malignancy (may cause cell lysis) contribute to hyperkalaemia following hypokalaemia. Caution with potassium suppletion and frequent monitoring of S(K) may prevent iatrogenic hyperkalaemia. PMID- 17848396 TI - Optimal dialysate calcium and vascular calcification. PMID- 17848397 TI - Successful pregnancy in a patient with end-stage renal failure secondary to HIV nephropathy on peritoneal dialysis. PMID- 17848398 TI - Improved detection of overrepresentation of Gene-Ontology annotations with parent child analysis. AB - MOTIVATION: High-throughput experiments such as microarray hybridizations often yield long lists of genes found to share a certain characteristic such as differential expression. Exploring Gene Ontology (GO) annotations for such lists of genes has become a widespread practice to get first insights into the potential biological meaning of the experiment. The standard statistical approach to measuring overrepresentation of GO terms cannot cope with the dependencies resulting from the structure of GO because they analyze each term in isolation. Especially the fact that annotations are inherited from more specific descendant terms can result in certain types of false-positive results with potentially misleading biological interpretation, a phenomenon which we term the inheritance problem. RESULTS: We present here a novel approach to analysis of GO term overrepresentation that determines overrepresentation of terms in the context of annotations to the term's parents. This approach reduces the dependencies between the individual term's measurements, and thereby avoids producing false-positive results owing to the inheritance problem. ROC analysis using study sets with overrepresented GO terms showed a clear advantage for our approach over the standard algorithm with respect to the inheritance problem. Although there can be no gold standard for exploratory methods such as analysis of GO term overrepresentation, analysis of biological datasets suggests that our algorithm tends to identify the core GO terms that are most characteristic of the dataset being analyzed. PMID- 17848399 TI - Reconstruction of the right atrium with pulmonary artery homograft after resection of right atrial lipomatosis. AB - We present a case of large right atrial mass due to lipomatous hypertrophy of the interatrial septum and left lower lobe adenocarcinoma. Combined resections of the right atrial mass with reconstruction of the superior atriocaval junction and right atrial free wall defects with pulmonary artery homograft and wedge excision of the lung tumor were performed through median sternotomy. PMID- 17848400 TI - Management of complicated postoperative air-leak - a new indication for the Asherman chest seal. AB - Postoperative air-leak is a problem which is frequently encountered in thoracic surgery. We describe the utility of the Asherman chest seal, a device used in primary trauma care in the successful management of a complicated postoperative air-leak. The Asherman Chest Seal is a sterile occlusive dressing with a one-way Heimlich valve for treating open pneumothorax in acute settings. We used the Asherman chest seal in six patients from July 2001-June 2006 for management of persistent air-leak following thoracic surgical procedures. It was used in three decortication and three pleurectomy patients. There was an equal sex distribution with an age range of 24-67 years. The chest seal was used when drains fell out in the presence of air-leak or wound infection resulting in pneumothorax. All six patients had satisfactory expansion of the lungs with cessation of the air-leak. This was achieved without the pain and morbidity of a chest drain and inpatient stay. The Asherman chest seal is a simple but very useful device that has a role in management of complex air-leaks. PMID- 17848401 TI - Accumulation of advanced glycation endproducts in patients with systemic lupus erythematosus. AB - OBJECTIVE: To investigate whether advanced glycation endproducts (AGEs) are increased in patients with systemic lupus erythematosus (SLE), and are related to atherosclerosis, which is accelerated in SLE, and its traditional and non traditional disease-related risk factors. METHODS: Fifty-five SLE patients with inactive disease and 55 age- and sex-matched controls were included. The amount of skin autofluorescence (AF), as a measure for the accumulation of AGEs, was assessed by measuring UV-A light excitation-emission matrices (AF-EEMS). Traditional risk factors and disease-related factors were recorded. Plasma levels of C-reactive protein (CRP), as a marker for systemic inflammation, were assessed. Intima-media thickness (IMT) of the common carotid artery was determined by ultrasound. RESULTS: Skin AF-EEMS was increased in SLE patients as compared with controls (1.50 +/- 0.5 a.u. vs 1.28 +/- 0.4 a.u., P = 0.006). Regarding all included risk factors, univariate analyses in patients revealed that AF-EEMS was associated with age (r = 0.48, P < 0.001), IMT (r = 0.35, P = 0.01), creatinine (r = 0.29, P = 0.03), SLICC damage index (r = 0.29, P = 0.03) and disease duration (r = 0.32, P = 0.02). In multivariate analysis, age and disease duration were independent predictors of accumulation of AGEs in SLE (P < 0.001, P = 0.03, respectively). CONCLUSION: AGEs are increased in SLE compared with controls. Our findings indicate that AGE accumulation is associated with disease duration and might contribute to the development of accelerated atherosclerosis in SLE and, therefore, could be used for assessment of risk for long-term vascular complications. PMID- 17848402 TI - Preventive strategies for group B streptococcal and other bacterial infections in early infancy: cost effectiveness and value of information analyses. AB - OBJECTIVE: To determine the cost effectiveness of strategies for preventing neonatal infection with group B streptococci and other bacteria in the UK and the value of further information from research. DESIGN: Use of a decision model to compare the cost effectiveness of prenatal testing for group B streptococcal infection (by polymerase chain reaction or culture), prepartum antibiotic treatment (intravenous penicillin or oral erythromycin), and vaccination during pregnancy (not yet available) for serious bacterial infection in early infancy across 12 maternal risk groups. Model parameters were estimated using multi parameter evidence synthesis to incorporate all relevant data inputs. DATA SOURCES: 32 systematic reviews were conducted: 14 integrated results from published studies, 24 involved analyses of primary datasets, and five included expert opinion. Main outcomes measures Healthcare costs per quality adjusted life year (QALY) gained. RESULTS: Current best practice (to treat only high risk women without prior testing for infection) and universal testing by culture or polymerase chain reaction were not cost effective options. Immediate extension of current best practice to treat all women with preterm and high risk term deliveries without testing (11% treated) would result in substantial net benefits. Currently, addition of culture testing for low risk term women, while treating all preterm and high risk term women, would be the most cost effective option (21% treated). If available in the future, vaccination combined with treating all preterm and high risk term women and no testing for low risk women would probably be marginally more cost effective and would limit antibiotic exposure to 11% of women. The value of information is highest (67m pounds sterling) if vaccination is included as an option. CONCLUSIONS: Extension of current best practice to treat all women with preterm and high risk term deliveries is readily achievable and would be beneficial. The choice between adding culture testing for low risk women or vaccination for all should be informed by further research. Trials to evaluate vaccine efficacy should be prioritised. PMID- 17848403 TI - Mid-luteal endometrial intracrinology following controlled ovarian hyperstimulation involving use of a gonadotrophin releasing hormone antagonist. AB - BACKGROUND: There are concerns of reduced pregnancy rates with the use of gonadotrophin-releasing hormone antagonists (GnRH antagonists) in IVF/ICSI cycles. Sex steroids and their metabolizing enzymes in the endometrium may play a vital role in embryo implantation. This study has evaluated the levels and localization of sex-steroid receptors and metabolizing enzymes, 3beta hydroxysteroid dehydrogenases (3betaHSD) and selected 17beta-HSD (17betaHSD), in mid-luteal endometrium of women treated with GnRH antagonist (Cetrorelix) and recombinant FSH (rFSH; Gonal-F) with luteal phase progesterone supplementation. METHODS: Mid-luteal phase endometrial biopsies were obtained from oocyte donors undergoing ovarian stimulation and from control women with regular periods. Immunohistochemistry and real-time quantitative-polymerase chain reaction (QRT PCR) were used to compare protein and mRNA expression of progesterone receptor (PR), estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), androgen receptor (AR), 3betaHSD1, 3betaHSD2, 17betaHSD2 and 17betaHSD5. RESULTS: Cetrorelix-rFSH treatment caused a mid-luteal suppression of PR protein expression in the endometrial stroma, surface epithelium and glands, although expression in the glands of control samples was variable. In contrast, the treatment caused an increase in PR staining in perivascular cells. No other significant differences in protein expression were observed between the two groups. mRNA levels of AR, ERalpha, 3betaHSD1 and 17betaHSD2 were significantly reduced in the treatment group. PR mRNA levels were also reduced by GnRH antagonist-rFSH treatment, but the difference was not significant. CONCLUSIONS: Changes in the expression of sex-steroid receptors and metabolizing enzymes may lead to alterations in the activity and intracellular availability of estrogens, progestogens and androgens in endometrium of women treated with Cetrorelix and rFSH. Their impact on embryo implantation merits further evaluation. PMID- 17848404 TI - Human fetal testis Leydig cell disruption by exposure to the pesticide dieldrin at low concentrations. AB - BACKGROUND: Declining human reproductive health over the last 60 years has been proposed to be due to effects of environmental chemicals, especially endocrine disrupting compounds, on fetal development. We investigated whether a model pesticide, dieldrin, at concentrations within both maternal circulation and environmental ranges (1 pmol/l = 0.0004 p.p.b. = 380.9 pg/l), could disrupt the human fetal testis. METHODS: Human fetal testes were collected during the second trimester, a critical period of male sexual differentiation (development and masculinization). Testis explants were cultured for 24 h in the presence and absence of LH (10-1000 IU LH/l) and dieldrin (1 pmol and 1 nmol/l). Endocrine, immunohistological and proteome characteristics of the tissues were investigated. RESULTS: Exposure to dieldrin reduced LH-induced testosterone secretion (P < 0.05) and tissue protein concentrations of LH receptor and steroid acute regulatory protein (P < 0.05). Dieldrin altered proteins associated with cancer, apoptosis, transcription and development. Wnt-2b was reduced 3-fold and immunolocalized to Leydig and Sertoli cells. Dieldrin also reversed some LH induced changes in protein expression, supporting the conclusion that Leydig cell function is at risk from environmental chemicals. CONCLUSIONS: Our findings indicate that exposure to very low, biologically relevant, concentrations of environmental chemicals could affect the fetal human Leydig cell, reducing testosterone secretion and potentially leading to subtle dysregulation of reproductive development and adult fecundity. PMID- 17848405 TI - Body size at birth predicts hypothalamic-pituitary-adrenal axis response to psychosocial stress at age 60 to 70 years. AB - BACKGROUND: Studies in humans and animals have suggested intrauterine programming of hypothalamic-pituitary-adrenal axis (HPAA) function as an important mechanism in linking fetal life conditions with adult disease. OBJECTIVE: Our aim was to assess how body size at birth, a marker of intrauterine conditions, is associated with hypothalamic-pituitary-adrenal axis response to psychosocial stress in late adulthood. DESIGN AND SETTING: We conducted a clinical study in the Helsinki Birth Cohort. PARTICIPANTS: Two hundred eighty-seven men and women born between 1934 and 1944 whose birth measurements and gestational age came from hospital records participated in the study. MEASUREMENTS: We measured salivary cortisol and, for 215 individuals, plasma cortisol and ACTH concentrations in conjunction with a standardized psychosocial stressor (Trier Social Stress Test). RESULTS: There was a linear relationship between low birth weight and low plasma ACTH but no linear relationship with cortisol. There were, however, quadratic relationships between birth weight and salivary (mixed model P = 0.001) and plasma cortisol (P = 0.005) but not with plasma ACTH (P = 0.1). The lowest peak salivary cortisol concentrations were seen in the lowest third of birth weights (adjusted for gestational age and sex): 12.9 nmol/liter (95% confidence interval of mean 11.2-15.0), compared with 17.1 nmol/liter (14.8-19.8) in the middle and 14.1 nmol/liter (12.6-15.7) in the highest third of birth weights. Corresponding figures for plasma cortisol were 418 nmol/liter (380-459), 498 nmol/liter (455 545), and 454 nmol/liter (428-482), and for plasma ACTH 8.17 pmol/liter (6.98 9.57), 12.42 pmol/liter (10.64-14.51), and 11.50 (10.06-13.14), respectively. Results for areas under the curve were similar. CONCLUSIONS: We found an inverse U-shaped relationship between birth weight and cortisol concentrations during psychosocial stress. The lowest cortisol and ACTH concentrations were seen in subjects with the lowest birth weights. These results support the hypothesis that both hyper- and hypocortisolism may be programmed during the fetal period. PMID- 17848406 TI - Young obese women with polycystic ovary syndrome have evidence of early coronary atherosclerosis. AB - CONTEXT: Polycystic ovary syndrome (PCOS) is associated with comorbidities that may contribute to increased risk of cardiovascular disease. PCOS is associated with increased risk of metabolic syndrome, dyslipidemia, and diabetes, but it remains unclear whether traditional cardiovascular (CV) risk factors can help predict coronary artery disease in this population. OBJECTIVE: The objectives of the study were to detect early-onset subclinical coronary atherosclerosis (using coronary artery calcium as a marker) in young women with PCOS, compared with age- and body mass index-matched controls, and to compare traditional CV risk factors and inflammatory markers in the two groups. DESIGN: This was a prospective case control study. SETTING: The study was conducted at a university hospital. SUBJECTS: Twenty-four obese (body mass index >or= 30 kg/m2) PCOS subjects and 24 obese controls participated. OUTCOME MEASURES: Coronary artery calcium, inflammatory markers (high-sensitivity C-reactive protein, IL-6, TNFalpha, adiponectin, leptin), fasting blood tests (glucose, lipids, insulin), and dual energy x-ray absorptiometry scan for body fat distribution were measured. RESULTS: Coronary artery calcium was detected in eight of 24 PCOS subjects (33%) and two of 24 controls (8%) (odds ratio 5.5, 95% confidence interval 1.03, 29.45, P < 0.03). Traditional CV risk factors did not differ significantly between the two groups, nor did markers of inflammation or adiposity, body fat distribution, or metabolic parameters with the exception of significantly lower quantitative insulin sensitivity check index (marker for insulin resistance) in the PCOS group (P < 0.05). CONCLUSIONS: Young, obese women with PCOS have a high prevalence of early asymptomatic coronary atherosclerosis, compared with obese controls. This increased risk is independent of traditional CV risk factors and novel markers of inflammation. These findings underscore the need to screen and aggressively counsel and treat these women to prevent symptomatic CV disease. PMID- 17848407 TI - Early metabolic derangements in daughters of women with polycystic ovary syndrome. AB - CONTEXT: Polycystic ovary syndrome (PCOS) is a familial endocrine-metabolic dysfunction, increasingly recognized in adolescent girls with hyperandrogenism. However, it is difficult to establish whether the metabolic abnormalities described in PCOS are present before the onset of hyperandrogenism. In children, a strong association of adiponectin levels with metabolic parameters of insulin resistance has been described. OBJECTIVE: The objective of the study was to evaluate adiponectin serum concentrations and metabolic parameters in prepubertal and pubertal daughters of women with PCOS to identify girls with increased metabolic risk. DESIGN: Fifty-three prepubertal and 22 pubertal (Tanner stages II V) daughters of PCOS women (PCOSd) and 32 prepubertal and 17 pubertal daughters of control women (Cd) were studied. In both groups, an oral glucose tolerance test was performed with measurement of glucose and insulin. Adiponectin, leptin, C-reactive protein, SHBG, sex steroids, and lipids were determined in the fasting sample. RESULTS: Both groups had similar chronological ages, body mass index sd score, and Tanner stage distribution. In the prepubertal girls, 2-h insulin was higher (P = 0.023) and adiponectin levels were lower (P = 0.004) in the PCOSd group, compared with the Cd group. In the pubertal girls, triglycerides (P = 0.03), 2-h insulin (P = 0.01), and serum testosterone concentrations were higher (P = 0.012) and SHBG lower (P = 0.009) in PCOSd, compared with Cd, but adiponectin levels were similar in both groups. CONCLUSIONS: Some of the metabolic features of PCOS are present in daughters of PCOS women before the onset of hyperandrogenism. Adiponectin appears to be one of the early markers of metabolic derangement in these girls. PMID- 17848408 TI - Bcl-2 overexpression in thyroid carcinoma cells increases sensitivity to Bcl-2 homology 3 domain inhibition. AB - CONTEXT: The Bcl-2 family of proteins regulates apoptosis in various models and may represent a promising therapeutic target in human malignancies. OBJECTIVE/METHODS: We evaluated the sensitivity of thyroid carcinoma cell lines (two papillary, one follicular, two anaplastic, three medullary) in vitro to BH3I 1 and BH3I-2', two cell-permeable inhibitors of the Bcl-2 homology (BH)-3 domain mediated interaction between proapoptotic and antiapoptotic Bcl-2 family members. The thyroid carcinoma cell line FRO was stably transfected with cDNA for Bcl-2 or constitutively active Akt and evaluated for sensitivity to BH3-domain inhibition. RESULTS: BH3-domain inhibition disrupted the mitochondrial membrane potential in thyroid carcinoma cells, induced caspase-dependent apoptosis, and potently sensitized them to sublethal concentrations of doxorubicin and the proteasome inhibitor bortezomib (Velcade). Overexpression of constitutively active Akt suppressed BH3I-1-induced cell death. Bcl-2-overexpressing FRO cells were more resistant to conventional chemotherapeutic agents (such as doxorubicin) but significantly more sensitive to BH3I-1 than control cells and were found to overexpress caspase-9, caspase-8, Bmf, Bok, and Bik transcripts and express less A1, BRaf, and FLIP transcripts. CONCLUSIONS: Bcl-2 expression protects thyroid carcinomas against chemotherapy-induced apoptosis. Nevertheless, overexpression of Bcl-2 may result in "oncogene addiction" of the cancer cell, which can be exploited by using BH3-domain inhibitors alone or in combination with other agents, including conventional chemotherapeutics (such as doxorubicin) or novel targeted therapies (such as the proteasome inhibitor bortezomib), for the treatment of aggressive thyroid cancer, including the medullary and anaplastic types. PMID- 17848409 TI - Compound heterozygosity for mutations in LMNA in a patient with a myopathic and lipodystrophic mandibuloacral dysplasia type A phenotype. AB - CONTEXT: Mandibuloacral dysplasia type A (MADA; OMIM 248370) is a rare progeroid syndrome characterized by dysmorphic craniofacial and skeletal features, lipodystrophy, and metabolic complications. Most Italian patients carry the same homozygous missense mutation (p.R527H) in the C-terminal tail domain of the LMNA gene, which encodes lamin A/C, an intermediate filament component of the nuclear envelope. OBJECTIVE: The objective of the study was to identify novel LMNA mutations in individuals with clinical characteristics (bird-like facies, mandibular and clavicular hypoplasia, acroosteolysis, lipodystrophy, alopecia) observed in other well-known patients. DESIGN: The LMNA gene was sequenced. Functional properties of the mutant alleles were investigated. PATIENT: We report a 27-yr-old Italian woman showing a MADA-like phenotype. Features include a hypoplastic mandible, acroosteolysis, pointed nose, partial loss of sc fat, and a progeric appearance. Due to the absence of clavicular dysplasia and normal metabolic profiles, generally associated with muscle hyposthenia and generalized hypotonia, this phenotype can be considered an atypical laminopathy. RESULTS: We identified a patient compound heterozygote for the p.R527H and p.V440M alleles. The patient's cells showed nuclear shape abnormalities, accumulation of pre-lamin A, and irregular lamina thickness. Lamins A and C showed normal expression and localization. The electron microscopy detected heterochromatin defects with a pattern similar to those observed in other laminopathies. However, chromatin analysis showed a normal distribution pattern of the major heterochromatin proteins: heterochromatin protein-1beta and histone H3 methylated at lysine 9. CONCLUSIONS: The clinical and cellular features of this patient show overlapping laminopathy phenotypes that could be due to the combination of p.R527H and p.V440M alleles. PMID- 17848410 TI - The 23K variant of the R23K polymorphism in the glucocorticoid receptor gene protects against postnatal growth failure and insulin resistance after preterm birth. AB - CONTEXT: Preterm birth is associated with postnatal growth failure, abdominal fat accumulation, insulin resistance, and hypertension, resembling increased glucocorticoid bioactivity. OBJECTIVE: We tested the effects of the R23K and N363S polymorphisms in the glucocorticoid receptor gene, associated with decreased and increased sensitivity to cortisol, respectively, on linear growth and the adult metabolic profile in a cohort (n = 249) of men and women born less than 32 gestational weeks and followed up prospectively from birth until 19 yr of age. DESIGN AND PARTICIPANTS: This was a birth cohort study that included 249 19 yr-old survivors born at a gestational age less than 32 wk from the Dutch Project on Preterm and Small-for-Gestational-Age Infants cohort. SETTING: This project was a nationwide multicenter follow-up study. MAIN OUTCOME MEASURES: Linear growth and adult body composition, fasting cortisol, glucose, insulin, and cholesterol concentrations, and blood pressure were measured. RESULTS: The 23K variant (n = 24) was associated with lower fasting insulin levels [mean difference after log transformation: -0.09 (95% confidence interval -0.16, -0.01) mU/liter] and a lower homeostatic model assessment for insulin resistance index [mean difference after log transformation: -0.09 (95% confidence interval -0.16, 0.01)] as well as with a taller stature departing from the age of 1 yr onward. 23K carriers showed complete catch-up growth between the ages of 3 months and 1 yr, and attained height was similar to the population reference mean, whereas stature in noncarriers was on average 0.5 sd below this mean. In contrast, the N363S polymorphism was not associated with any of the outcomes. CONCLUSIONS: Carriers of the 23K variant are, at least in part, protected against postnatal growth failure and insulin resistance after preterm birth. PMID- 17848411 TI - Developmental changes in human fetal testicular cell numbers and messenger ribonucleic acid levels during the second trimester. AB - CONTEXT: Normal fetal testis development is essential for masculinization and subsequent adult fertility. The second trimester is a critical period of human testicular development and masculinization, but there is a paucity of reliable developmental data. OBJECTIVE: The objective of the study was to analyze second trimester human testicular morphology and function. DESIGN: This was an observational study of second-trimester testis development. SETTING: The study was conducted at the Universities of Glasgow and Aberdeen. PATIENTS/PARTICIPANTS: Testes were collected from 57 morphologically normal fetuses of women undergoing elective termination of normally progressing pregnancies (11-19 wk gestation). MAIN OUTCOME MEASURE(S): Testicular morphology, cell numbers, and quantitative expression of 22 key testicular genes were determined. RESULTS: Sertoli cell and germ cell number increased exponentially throughout the second trimester. Leydig cell number initially increased exponentially but slowed toward 19 wk. Transcripts encoding Sertoli (KITL, FGF9, SOX9, FSHR, WT1) and germ (CKIT, TFAP2C) cell-specific products increased per testis through the second trimester, but expression per cell was static apart from TFAP2C, which declined. Leydig cell transcripts (HSD17B3, CYP11A1, PTC1, CYP17, LHR, INSL3) also remained static per cell. Testicular expression of adrenal transcripts MC2R, CYP11B1, and CYP21 was detectable but unchanged. Expression of other transcripts known or postulated to be involved in testicular development (GATA4, GATA6, CXORF6, WNT2B, WNT4, WNT5A) increased significantly per testis during the second trimester. CONCLUSIONS: The second trimester is essential for the establishment of Sertoli and germ cell numbers. Sertoli and Leydig cells are active throughout the period, but there is no evidence of changing transcript levels. PMID- 17848412 TI - High frequency of germline succinate dehydrogenase mutations in sporadic cervical paragangliomas in northern Spain: mitochondrial succinate dehydrogenase structure function relationships and clinical-pathological correlations. AB - PURPOSE: Germline SDHB, SDHC, and/or SDHD mutations have been reported in familial and apparently sporadic paragangliomas (PGLs). There is, however, some variation in the prevalence, penetrance, and phenotypic expression of the succinate dehydrogenase (SDH) mutated gene among different populations. We sought to determine whether germline mutations in SDHB, SDHC, and/or SDHD play a role in cervical PGLs from northern Spain, where this disorder is particularly frequent, and whether there is any difference with respect to the data published in other populations. DESIGN: Thirty-six sporadic cervical PGLs and four familial PGLs were investigated by PCR-single-strand conformation polymorphism analysis and sequencing. Computational biology was applied to address the structural conformational changes behind missense mutations and, simultaneously, infer the possible consequences in protein function. RESULTS: Eight sporadic cases (22.2%) carried pathogenic germline mutations, six of which were in SDHB and two in SDHD. Three families had mutations in SDHD and one in SDHB. Seven of 11 different pathogenic mutations (64%) affected SDHB. Ten mutations were novel. Missense mutations were primarily found in SDHB and frameshift mutations in SDHD. Missense SDHB mutations seemed to alter the enzymatic activity by hampering the electron transfer. SDH-linked tumors occurred mainly in males (P = 0.0033), occurred at a younger age (P < 0.0001), were usually multifocal (P = 0.0011), and exhibited a larger size (P = 0.0341). CONCLUSIONS: A significant proportion of sporadic cervical PGLs arise as a consequence of intrinsic genetic factors. At variance with previous reports, SDHB is frequently mutated in sporadic cervical PGLs and the mutations do not entail a deleterious behavior. Therefore, SDHB genetic testing may be considered in all subjects presenting with solitary cervical PGL and no family history. PMID- 17848413 TI - Substitution of the use of radioactivity by fluorescence for biochemical studies of RNA. AB - We present here the use of fluorescent methodologies for structural and functional studies of RNA in place of radioactivity. The methods are highly sensitive and quantitative with the use of an infrared fluorescence imaging system. IRD-700 and IRD-800 labels are used for fluorescence detection. Chemical probing methods are largely used for mapping RNA secondary structure and to monitor ligand interactions and conformational changes involving individual bases of RNA. The new fluorescent primer extension methodology allows simple and fast chemical probing of RNA with high sensitivity. IRD-700 and IRD-800 labeled primers can also be used to monitor protein-RNA interactions by fluorescent mobility shift assays. The speed and ease of these approaches are advantages over prior methods that used hazardous radioisotopes. Structural and biochemical investigations of RNA should benefit from the use of these fluorescent methodologies. PMID- 17848415 TI - A pharmacist-based toxicology service. 1978. PMID- 17848414 TI - Polymorphism of the GRTH/DDX25 gene in normal and infertile Japanese men: a missense mutation associated with loss of GRTH phosphorylation. AB - The gonadotropin-regulated testicular RNA helicase (GRTH/Ddx25) is present in Leydig and germ cells of rodents, and is essential for fertility in mice. This study evaluated the incidence of GRTH/DDX25 gene mutations in a group of infertile patients with non-obstructive azoospermia (NOA), 85% with a preponderance of Sertoli cells in the seminiferous tubule and 15% with spermatogenic arrest, and compared them to a group of fertile subjects. Exonic sequences in the GRTH gene were screened using denaturing high-performance liquid chromatography of the genomic DNA from 143 NOA and 100 fertile Japanese men. A unique heterozygous missense mutation Arg(242)His in exon 8 was identified in 5.8% of Sertoli cell-only patients and in 1% of normal subjects. Although the mutant protein was efficiently expressed in COS-1 cells, only the 56 kDa nuclear/cytoplasmic non-phosphorylated species was present, whereas the 61 kDa cytosolic phosporylated species was absent. In addition, a silent mutation was identified in exon 11 in NOA subjects. The Arg(242)His missense mutation of the GRTH/DDX25 gene associated with expression of a protein with reduced basicity, and the absence of the phospho-GRTH species, could be of relevance to some of the functional aspects of the protein that impact on germ cell development and/or function. PMID- 17848416 TI - Economic impact of pharmacists' interventions with nonsteroidal antiinflammatory drugs. 2003. PMID- 17848417 TI - Pharmacists as clinical toxicologists: reflections on evolution, challenges, and opportunities. PMID- 17848418 TI - Evolution of clinical pharmacy in the practice of rheumatology. PMID- 17848419 TI - HPV vaccine: immersed in controversy. AB - There has been substantial media coverage of the quadrivalent human papillomavirus (HPV) vaccine since the Food and Drug Administration approved Gardasil (Merck & Co., Inc.) on June 8, 2006. The most vocal complaints maintain that its use will promote promiscuity among teenagers, and condemn proposed mandated use for school entry. Some also question evidence for the vaccine's safety. There have been concerns raised by both providers and patients regarding financial barriers to access. Still others argue that additional populations could benefit who have not been included in current recommendations. Clarification of these issues is essential to advance optimal use of this important new vaccine. There is strong evidence to support HPV vaccine as an effective, safe, and efficient public health measure. School mandates are valuable tools to reduce disparities in availability of immunizations. The time has come to consider universal funding as a means to improve access to all recommended vaccines. PMID- 17848420 TI - Inappropriate continuation of stress ulcer prophylactic therapy after discharge. AB - BACKGROUND: Medications for stress ulcer prophylaxis are appropriately started in critically ill patients with risks for developing stress ulcers. It is unknown whether these drugs are discontinued once the risk factors are removed. OBJECTIVE: To assess the duration of stress ulcer prophylactic therapy in critically ill patients. METHODS: A retrospective chart review was conducted at a multidisciplinary, 24 bed medical/surgical intensive care unit (ICU) of a university-affiliated tertiary referral medical center. Three hundred ninety-four patients fulfilled eligibility criteria during the study period of July 1, 2005, through September 30, 2005. Patients were considered to be appropriately discharged from the hospital on gastric acid suppressants if they met any of the following criteria: continued mechanical ventilation, gastroesophageal reflux disease, peptic ulcer disease, history of gastrointestinal ulceration or bleeding within the past year, prescribed medications used for stress ulcer prophylaxis prior to admission, gastrointestinal bleed during hospitalization, or prescriber indication of reason to continue therapy. RESULTS: Three hundred fifty-seven patients received stress ulcer prophylaxis during their ICU stay. Of these, 80% continued on gastric acid suppressants on transfer from the ICU, with 60% of the therapy being inappropriate. The percentage of critically ill patients discharged from the hospital with inappropriate prescription of gastric acid suppressants was 24.4%. Based on the average wholesale cost, the total cost for unnecessary gastric acid suppressant therapy within the follow-up period was $13,973. CONCLUSIONS: Gastric acid suppressant medications initially prescribed for stress ulcer prophylaxis are frequently prescribed inappropriately on discharge for patients who were initially admitted to the medical/surgical ICU. PMID- 17848421 TI - Role of chemotherapy and rituximab for treatment of posttransplant lymphoproliferative disorder in solid organ transplantation. AB - OBJECTIVE: To evaluate the role of chemotherapy and/or rituximab for treatment of posttransplant lymphoproliferative disorder (PTLD) in solid organ transplantation. DATA SOURCES: A MEDLINE search (1966-May 2007) was conducted using the key words posttransplant lymphoproliferative disorder, solid organ transplantation, chemotherapy, and rituximab. References of relevant articles and abstracts from recent hematology, oncology, and transplantation scientific meetings (2004-May 2007) were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Prospective and retrospective studies identified from the data sources were evaluated, and all information deemed relevant was included for this review. DATA SYNTHESIS: Overall response rates ranged from 53% to 68%, 25% to 83%, and 74% to 100% for rituximab monotherapy, chemotherapy, and chemotherapy plus rituximab, respectively. Positive response to treatment was influenced by prognostic factors, including presence of Epstein-Barr virus in tumor cells, normal lactate dehydrogenase levels, good performance status, early disease onset after transplantation, and early disease stages. These factors in study patients likely contribute to the variability in response rates seen between treatment options. Severe adverse effects, ranging from grade 3 neutropenia to infection resulting in death, occurred more frequently in patients receiving chemotherapy than in patients receiving only rituximab. CONCLUSIONS: Although reduction in immunosuppressive medications remains the first-line therapy for PTLD treatment, many cases do not respond to this treatment alone, especially monomorphic or more aggressive cases of lymphoma. Therefore, it is reasonable to begin active treatment including rituximab and/or chemotherapy initially, along with reduction in immunosuppression in many cases. Further prospective, comparative studies are urgently needed to confirm the efficacy of these treatment strategies as well as to clarify which subset of patients may benefit most from them. PMID- 17848422 TI - Evaluation of centrally acting cholinesterase inhibitor exposures in adults. AB - BACKGROUND: There are 4 centrally acting cholinesterase inhibitors (CA-ChEI) available in the US: tacrine, galantamine, rivastigmine, and donepezil. Documented clinical experience involving exposure to these agents is limited. The lack of information makes decisions involving excessive or unintended CA-ChEI exposure difficult. OBJECTIVE: To assess the effects, demographics, and outcomes of CA-ChEI exposures reported to US poison centers. METHODS: A retrospective review of the Toxic Exposure Surveillance System of the American Association of Poison Control Centers data of acute and acute-onchronic exposures involving only a CA-ChEI in patients 19 years of age or older with documented medical outcomes from 2000-2005 was performed. RESULTS: There were 1026 records that met criteria for this study. Patients aged 70-89 years made up 73% of reports; 69% of the patients were female. Moderate (197) and major outcomes (20) accounted for 21% of exposures. There were no deaths. Clinical effects that occurred in 5% or more of patients included vomiting (34%), nausea (28%), diarrhea (12%), dizziness/vertigo (9.9%), drowsiness/lethargy (7.7%), diaphoresis (7.4%), tremor (5.2%), and bradycardia (5%). Patients were admitted to the hospital in 19% of all exposures. Of those patients, 42% were admitted to a critical care unit. The majority (65%) of exposures were attributed to unintentional therapeutic error. Patients received at least one form of therapy in 47% of exposures, including intravenous fluid (111), antiemetic (48), atropine (17), benzodiazepine (15), oxygen (14), antihypertensive (4), pralidoxime (4), intubation (3), antihistamine (2), antiarrhythmic (1), anticonvulsant (1), and pacemaker (1). CONCLUSIONS: The majority of patients evaluated in this retrospective study experienced no or mild effect; however, significant or life-threatening effects were observed in a small group of patients and an appreciable number of patients were admitted to a healthcare facility. PMID- 17848423 TI - Emergency department management of pediatric asthma at a university teaching hospital. AB - BACKGROUND: Asthma is a major health problem and the most frequent cause of chronic illness and emergency department (ED) visits in children. Limited data examining the ED management of pediatric asthma within university teaching hospitals across the US exist. OBJECTIVE: To compare the ED management of children (aged 1-17 y) with asthma at a university teaching hospital using National Asthma Education and Prevention Program (NAEPP) guidelines. METHODS: All cases of pediatric asthma that presented to the University of California, San Francisco, Medical Center ED between October 1, 2003, and October 31, 2004, were included. Patients who required hospital admission were excluded. Data pertaining to patient demographics, primary diagnosis, pharmacologic management, diagnostic tests performed, and follow-up plans were abstracted and compared with NAEPP guidelines issued in 1997 and updated topics released in 2002. RESULTS: A total of 141 cases were identified. Mean patient age was 5.8 years. Most (61.7%) patients were male and of African American ethnicity (31.9%). Asthma severity was typically mild (66.7%) or moderate (29.1%). In persons at least 6 years of age (n = 58), peak expiratory flow rate (PEFR) was performed in 25.9% of cases. Pulse oximetry, however, was always performed. Based on NAEPP guidelines, beta-agonists and corticosteroids should have been used, but were not, in 2.8% and 31.9% of cases, respectively. At discharge, no corticosteroid prescription was given in 40.4% of the cases, no written action plan was prepared in 80.1% of the cases, no formal device training was administered in 67.3% of cases, and no peak flow meter was provided for persons at least 6 years of age in 50.0% of cases. CONCLUSIONS: NAEPP guidelines were met in all patients regarding pulse oximetry and in most patients with respect to the use of beta-agonists. Improvements could be made, however, in the use of corticosteroids in the ED; in performing PEFR measurements for persons at least 6 years of age upon arrival; and in providing formal device training, a written action plan, prescriptions for steroids, and peak flow meters at discharge. PMID- 17848424 TI - Escitalopram therapy for major depression and anxiety disorders. AB - BACKGROUND: Randomized controlled clinical trials have demonstrated that escitalopram is efficacious in a range of mood and anxiety disorders, but the individual trials are insufficiently large to allow a full exploration of its tolerability. OBJECTIVE: To assess the tolerability and safety of escitalopram through analysis of all randomized controlled clinical trials in major depressive disorder and anxiety disorders. METHODS: Analyses of tolerability were based on data from all available randomized, double-blind, controlled studies completed by December 2006 in which escitalopram was compared with placebo or active compounds (citalopram, fluoxetine, paroxetine, sertraline, venlafaxine). Adverse events (AEs) that occurred more frequently with escitalopram than with placebo were listed, and tolerability and safety were evaluated. RESULTS: Nausea was the only AE with an incidence greater than or equal to 10% and 5 percentage points greater than with placebo during short-term treatment. In general, AEs were mild to moderate in severity. AEs related to sexual dysfunction were similarly frequent with escitalopram and citalopram, but were higher with paroxetine. No suicide occurred among escitalopram-treated patients, and there were no significant differences between escitalopram and placebo in incidence of suicidal behavior, measured by self-harm and suicidal thoughts. The 8 week withdrawal rate due to AEs was higher with escitalopram than with placebo (7.3% vs 2.8%; p < 0.001) but lower than with paroxetine (6.6% vs 9.0%; p < 0.01) or venlafaxine (6.1% vs 13.2%; p < 0.01) (Fisher's Exact test, 2 tailed). Compared with paroxetine, escitalopram resulted in significantly fewer discontinuation symptoms (average increase in Discontinuation Emergent Signs and Symptoms Scale of 1.6 vs 3.9; p < 0.01). There were no clinically relevant changes in clinical laboratory values in patients treated with escitalopram. Mean weight change after 6 months of treatment with escitalopram (0.58 +/- 2.63 kg) was similar to that with placebo (0.15 +/- 2.33 kg). The incidence of cardiovascular events was similar to that with placebo. The risk of AEs was no higher in special patient populations, such as the elderly (> or =65 y of age) or those with hepatic dysfunction. CONCLUSIONS: Based on data from randomized controlled trials involving more than 4000 escitalopram-treated patients, escitalopram (10-20 mg/day) is safe and well tolerated in short- and long-term treatment. PMID- 17848425 TI - ISIS 301012 gene therapy for hypercholesterolemia: sense, antisense, or nonsense? AB - OBJECTIVE: To present an overview of antisense technology and to review and assess available literature on the chemistry, pharmacology, pharmacokinetics, drug interactions, preclinical and clinical studies, dosing, and adverse events of ISIS 301012 in the treatment of hyperlipidemia. DATA SOURCES: PubMed database searches were conducted from 1966 to May 2007 using the search terms ISIS 301012, antisense, oligonucleotide, hypercholesterolemia, hyperlipidemia, and apolipoprotein B. Bibliographies of relevant review articles and information from the manufacturer were reviewed for additional references. STUDY SELECTION AND DATA EXTRACTION: Available English-language literature, including abstracts, preclinical, and clinical trials, review articles, and scientific presentations were examined. DATA SYNTHESIS: Apolipoprotein B is an important structural protein on the surface of atherogenic lipoproteins such as remnant very-low density lipoprotein and low-density lipoprotein and facilitates the clearance of these particles from the circulation by binding to the low-density lipoprotein receptor. Overproduction of apolipoprotein B or reduced receptor-mediated clearance of lipoproteins leads to elevated serum cholesterol levels and premature atherosclerosis. ISIS 301012 is an antisense oligonucleotide that inhibits apolipoprotein B production by binding directly to and reducing the expression of apolipoprotein B messenger RNA. In a clinical trial, ISIS 301012 50 400 mg administered weekly via subcutaneous injection for 4 weeks reduced apolipoprotein B by 14.3-47.4% and low-density lipoprotein cholesterol by 5.9-40% at 55 days. The most frequent adverse event was injection-site erythema that resolved spontaneously. Studies are ongoing to further define the safety, efficacy, and pharmacokinetics of ISIS 301012 as add-on therapy in patients with heterozygous and homozygous familial hypercholesterolemia. No pharmacokinetic interactions have been demonstrated with ezetimibe and simvastatin. CONCLUSIONS: ISIS 301012 is the first agent to enter clinical trials utilizing an antisense mechanism for reducing the production of apolipoprotein B. Further studies are needed to verify its safety, efficacy, and position of therapy in the dyslipidemic patient. PMID- 17848426 TI - Adjunctive aripiprazole in combat-related posttraumatic stress disorder. PMID- 17848429 TI - Vulnerable people, groups, and populations: societal view. AB - Vulnerability, the susceptibility to harm, results from an interaction between the resources available to individuals and communities and the life challenges they face. Vulnerability results from developmental problems, personal incapacities, disadvantaged social status, inadequacy of interpersonal networks and supports, degraded neighborhoods and environments, and the complex interactions of these factors over the life course. The priority given to varying vulnerabilities, or their neglect, reflects social values. Vulnerability may arise from individual, community, or larger population challenges and requires different types of policy interventions--from social and economic development of neighborhoods and communities, and educational and income policies, to individual medical interventions. PMID- 17848430 TI - How useful is 'vulnerable' as a concept? AB - The relationship between socioeconomic status, ethnicity, and chronic illness, on the one hand, and health status, access to health services, and quality of health care received, on the other, is a central and critical axis of health services research and health policy. However, it is not clear that the use of the term "vulnerable" to apply to individuals, groups, or populations helps very much from either an analytic or a policy perspective. This brief essay explores two instances of "vulnerability" far outside the prevailing paradigm, and it further identifies problems with the term. PMID- 17848431 TI - Making a difference in differences for the health inequalities of individuals. AB - Policy interventions should focus on the degree to which health conditions are persistent, avoidable, and treatable. Assistance should be targeted to people who are at greater risk for such conditions amid the most pronounced gaps between their available resources and likely economic needs. The highest-yield interventions should address prenatal and early childhood care and reformation of destructive lifestyle practices. Improving outreach, education, convenience of access, and service delivery represents a more important factor than expanding the level and scope of insurance coverage. Vulnerable people are better served by more pluralistic social processes that facilitate, but do not mandate, more effective choices and trade-offs. PMID- 17848432 TI - Early-life conditions and mechanisms of population health vulnerabilities. AB - The social status of groups is key to determining health vulnerability at the population level. The impact of material and psychological stresses imposed by social inequities and marginalization is felt most intensely during perinatal/early childhood and puberty/adolescent periods, when developmental genes are expressed and interact with social-physical environments. The influence of chronic psychosocial stresses on gene expression via neuroendocrine regulatory dysfunction is crucial to understanding the biological bases of adult health vulnerability. Studying childhood biology vulnerabilities to neighborhood environments will aid the crafting of multifaceted, multilevel public policy interventions providing immediate benefits and compounded long-term population health yields. PMID- 17848433 TI - The social response to genetic conditions: beware of the antidiscrimination law. AB - Today's widespread political support for the Genetic Information Nondiscrimination Act of 2007 rests on the assumption that serious inequities can be eliminated if employers are forbidden from using people's genetic information when making employment decisions. However, this laudable objective runs into serious weaknesses in implementation. Forcing employers to bear the cost of achieving parity between genetically high-risk and low-risk workers will create labor-market distortions that will inevitably shrink insurance coverage for vulnerable populations with genetic abnormalities along with everyone else. A better approach would be to create a politically transparent system of government provided subsidies. PMID- 17848434 TI - Health policy approaches to population health: the limits of medicalization. AB - Because of a strong tendency to "medicalize" health status problems and to assume that their primary solution involves medical care, policymakers often focus on increased financial and geographic access to personal health services in policies aimed at populations that are vulnerable to poor health. This approach has produced real public health gains, but it has neglected key social and economic causes of health vulnerability and disparities. Although access to care is a necessary component of population health, concerted policy action in income security, education, housing, nutrition/food security, and the environment is also critical in efforts to improve health among socially disadvantaged populations. PMID- 17848435 TI - Immigrants and health care: sources of vulnerability. AB - Immigrants have been identified as a vulnerable population, but there is heterogeneity in the degree to which they are vulnerable to inadequate health care. Here we examine the factors that affect immigrants' vulnerability, including socioeconomic background; immigration status; limited English proficiency; federal, state, and local policies on access to publicly funded health care; residential location; and stigma and marginalization. We find that, overall, immigrants have lower rates of health insurance, use less health care, and receive lower quality of care than U.S.-born populations; however, there are differences among subgroups. We conclude with policy options for addressing immigrants' vulnerabilities. PMID- 17848436 TI - Preparing racially and ethnically diverse communities for public health emergencies. AB - The tragedy of Hurricane Katrina in New Orleans confirmed that effective implementation of public health preparedness programs and policies will require compliance from all racial and ethnic populations. This study reviews current resources and limitations and suggests future directions for integrating diverse communities into related strategies. It documents research and interventions, including promising models and practices that address preparedness for minorities. However, findings reveal a general lack of focus on diversity and suggest that future preparedness efforts need to fully integrate factors related to race, culture, and language into risk communication, public health training, measurement, coordination, and policy at all levels. PMID- 17848438 TI - Improving population health and reducing health care disparities. AB - The first goal of Healthy People 2010, to increase quality and years of healthy life, does not necessarily coincide with the second goal, to eliminate disparities among population groups. Improvement in the health of the total population without any reduction in relative disparities among racial and ethnic groups was the most frequent outcome at mid-decade for population-based Healthy People objectives. Strategies to maximize improvement in overall population health may have little or no impact on relative disparities or, indeed, may cause them to increase. An independent commitment to eliminating disparities may be necessary. PMID- 17848439 TI - Measuring racial and ethnic health care disparities in Massachusetts. AB - Reducing racial and ethnic disparities in the quality of health care is a national policy priority; collecting race and ethnicity data from patients is a necessary first step in identifying and addressing these disparities. Recognizing this, Boston and Massachusetts recently enacted race and ethnicity data collection regulations affecting all acute care hospitals in the city and state. This paper describes the regulations and early lessons learned from implementing these data collection efforts in three areas: the design of data collection tools, uses of the data for eliminating disparities, and the role of the policy process in such efforts. PMID- 17848441 TI - Spillovers and vulnerability: the case of community uninsurance. AB - This paper studies the uninsured as a vulnerable population. We contend that reducing the size of the uninsured population yields important spillover benefits to the insured population, benefits that go beyond a lower charity care burden. Evidence presented in this paper reinforces studies in the literature that show that problems of health services quality and access facing insured people increase when the proportion of uninsured people in their local communities is greater. The size of such spillover benefits is reduced if the local market is large enough to be segmented based on insurance status. PMID- 17848442 TI - Consumer-directed health care and the disadvantaged. AB - Broad adoption of "consumer-directed health care" would probably widen socioeconomic disparities in care and redistribute wealth in "reverse Robin Hood" fashion, from the working poor and middle classes to the well-off. Racial and ethnic disparities in care would also probably worsen. These effects could be alleviated by adjustments to the consumer-directed paradigm. Possible fixes include more progressive tax subsidies, tiering of cost-sharing schemes to promote high-value care, and reduced cost sharing for the less well-off. These fixes, though, are unlikely to gain traction. If consumer-directed plans achieve market dominance, disparities in care by class and race will probably grow. PMID- 17848443 TI - Lowering the barriers to consumer-directed health care: responding to concerns. AB - Consumer-directed health care is a potentially promising tool for moving toward more efficient use of health care resources. Tax policy has long been biased against health plans with significant patient cost sharing. Tax advantages created by health savings accounts (HSAs) began to change that, and proposed tax reforms could go even further. We assess various critiques of these plans, focusing on why they benefit not just the healthy and wealthy. Lower costs and more efficient health spending would help all patients and reduce uninsurance. Potential negative distributional effects are important but can be remedied more efficiently without distorting insurance design. PMID- 17848444 TI - Pharmacy benefit caps and the chronically ill. AB - In this paper we examine medication use among retirees with employer-sponsored drug coverage both with and without annual benefit limits. We find that pharmacy benefit caps are associated with higher rates of medication discontinuation across the most common therapeutic classes and that only a minority of those who discontinue use reinitiate therapy once coverage resumes. Plan members who reach their cap are more likely than others to switch plans and increase their rate of generic use; however, in most cases, the shift is temporary. Given the similarities between these plans and Part D, we make some inferences about reforms for Medicare. PMID- 17848445 TI - Insurance expansions: do they hurt those they are designed to help? AB - Seeking to redress health disparities across income and race, many policy-makers mandate health insurance benefits, presuming that equalized benefits will help equalize use of beneficial health services. This paper tests that presumption by measuring health care use by a diverse population with comprehensive health insurance. Focusing on use of mental health care and pharmaceuticals, it finds that even when insurance benefits and access are constant, whites and those with high incomes consume more of these benefits than other people do. This suggests that privileged classes extract more health care services even when everyone pays equal premiums for equal insurance coverage. PMID- 17848446 TI - Barriers to serving the vulnerable: thoughts of a former public official. AB - In an environment of limited resources, the question of who is deserving and undeserving of assistance becomes critical. Policymakers' biases about whether a health condition is self-inflicted, as well as their perceptions about whether treatments are truly effective, play a major role--often unstated--in the allocation of resources. PMID- 17848447 TI - 'Redefining health care': medical homes or archipelagos to navigate? AB - This paper provides an analysis of the structure of the health care delivery system, emphasizing physician group practices. The authors argue for comprehensive integrated delivery systems (IDSs). The jumping-off point for their analysis is the recently published Redefining Health Care: Creating Value-Based Competition on Results, by Michael Porter and Elizabeth Teisberg. The authors focus on the book's core idea that competitors should be freestanding integrated practice units (or "islands in archipelagos") versus IDSs (or "medical homes"). In any case, the authors contend that this issue should be resolved by competition to attract and serve informed, cost-conscious, responsible consumers on a level playing field. PMID- 17848448 TI - Adoption of health information technology in community health centers: results of a national survey. AB - To the extent that health information technology (IT) improves health care quality, differential adoption among providers that serve vulnerable populations may exacerbate health disparities. This first national survey of federally funded community health centers (CHCs) shows that although 26 percent reported some electronic health record (EHR) capacity and 13 percent have the minimal set of EHR functionalities, CHCs serving the most poor and uninsured patients were less likely to have a functional EHR. CHCs cited lack of capital as the top barrier to adoption. Ensuring comparable health IT capacity among providers that disproportionately serve disadvantaged patients will have increasing relevance for disparities; thus, monitoring adoption among such providers should be a priority. PMID- 17848449 TI - Would greater transparency and uniformity of health care prices benefit poor patients? AB - President Bush, the World Health Organization, and leading scholars have called for greater price transparency in health care. Prices are transparent when the buyer knows his or her price or knows prices paid by others, in advance. Transparent prices inform consumers of expected costs and reveal when sellers are charging high prices to poor people. Under some conditions, however, price transparency can increase prices paid by the poor, deter business entry in poor markets, reduce competition, lower investment, and mislead if inaccurately measured by a third party. We recommend alternative approaches to lowering prices for the poor and increasing efficiency. PMID- 17848450 TI - Direct-to-consumer advertisements for HIV antiretroviral medications: a progress report. AB - Direct-to-consumer (DTC) prescription drug advertisements for HIV anti retrovirals are controversial and have been criticized in the past for including deceptive images and underplaying HIV drug limitations. We sought to describe the state of recent DTC ads for HIV antiretrovirals in popular magazines by performing a content analysis of all complete DTC ads for antiretroviral medications appearing in eight national magazines during a one-year period. Current ads appear to have addressed previous concerns, but important problems still exist, such as failing to specify the medication's role in current treatment, to quantify drug efficacy, or to highlight life-threatening side effects. PMID- 17848451 TI - Medicare and cost-effectiveness analysis: time to ask the taxpayers. AB - Maintaining Medicare's affordability for taxpayers and beneficiaries is becoming harder. Although cost containment strategies have been proposed, using cost effectiveness analysis (CEA) to prioritize coverage decisions has not been among them. There is a widespread but largely untested perception that Americans are unwilling to accept limits in health care. We review existing evidence about the public's willingness to accept constraints and set health care priorities. We suggest that given the opportunity to weigh in on ethical and normative issues that surround CEA, members of the public are appropriate parties to engage in shaping Medicare's broadest resource allocation questions. PMID- 17848452 TI - Health benefits in 2007: premium increases fall to an eight-year low, while offer rates and enrollment remain stable. AB - This paper reports findings from a survey of 1,997 public and private employers with three or more workers, conducted during the first five months of 2007. Premiums increased 6.1 percent from spring 2006 to spring 2007--the lowest rate of increase since 1999. Enrollment in different types of health plans did not change significantly, and high-deductible health plans with a savings option did not experience major growth in enrollment. Despite the comparatively modest increase in premiums during a period of strong economic growth, the percentage of workers obtaining coverage from their employer remained statistically unchanged. PMID- 17848453 TI - Trends in the health of older Americans, 1970-2005. AB - The health of Americans age sixty-five and older has improved on nearly all major indicators: longevity, self-reported health, and functioning. Both health care services use and health spending have risen. The increased use of restorative procedures and prescription medicines suggests that medical advances have had an important role in the better health of older Americans. Factors that might limit prospects for future improvements include rising rates of obesity and diabetes, particularly among the middle-aged. PMID- 17848454 TI - Down in New Orleans. PMID- 17848455 TI - Breakfast at midnight. PMID- 17848456 TI - Disparities in health: perspectives of a multi-ethnic, multi-racial America. AB - This 2006 survey of 4,157 randomly selected U.S. adults compared perceptions of health care disparities among fourteen racial and ethnic groups to those of whites. Findings suggest that many ethnic minority groups view their health care situations differently and, often, more negatively than whites. A substantial proportion perceived discrimination in receiving health care, and many felt that they would not receive the best care if they were sick. Most differences remained when socioeconomic characteristics were controlled for. The variety of responses across racial groups demonstrates the importance of examining ethnic subgroups separately rather than combined into a single category. PMID- 17848457 TI - Separate and unequal: racial segregation and disparities in quality across U.S. nursing homes. AB - We describe the racial segregation in U.S. nursing homes and its relationship to racial disparities in the quality of care. Nursing homes remain relatively segregated, roughly mirroring the residential segregation within metropolitan areas. As a result, blacks are much more likely than whites to be located in nursing homes that have serious deficiencies, lower staffing ratios, and greater financial vulnerability. Changing health care providers' behavior will not be sufficient to eliminate disparities in medical treatment in nursing homes. Persistent segregation among homes poses a substantial barrier to progress. PMID- 17848458 TI - Access to specialty care and medical services in community health centers. AB - Although community health centers (CHCs) provide primary health services to the medically underserved and poor, limited access to off-site specialty services may lead to poorer outcomes among underinsured CHC patients. This study evaluates access to specialty health services for patients receiving care in CHCs, using a survey of medical directors of all federally qualified CHCs in the United States in 2004. Respondents reported that uninsured patients had greater difficulty obtaining access to off-site specialty services, including referrals and diagnostic testing, than did patients with Medicaid, Medicare, or private insurance. PMID- 17848459 TI - Restoring fiscal integrity to medicaid financing? AB - Using survey data, we examined Medicaid supplemental payments (SPs), including disproportionate-share hospital (DSH) and upper payment limit (UPL) payments in 2005 and changes in these payments between 2001 and 2005. We found that states increased their use of general funds in financing of DSH payments while expanding the size and scope of other SPs considerably. Although the federal government has made some headway in reforming state Medicaid financing, our findings suggest that more work remains. PMID- 17848460 TI - Health spending in OECD countries in 2004: an update. AB - In 2004, U.S. health care spending per capita was 2.5 times greater than health spending in the median Organization for Economic Cooperation and Development (OECD) country and much higher than health spending in any other OECD country. The United States had fewer physicians, nurses, hospital beds, doctor visits, and hospital days per capita than the median OECD country. Health care prices and higher per capita incomes continued to be the major reasons for the higher U.S. health spending. One possible explanation is higher prevalence of obesity-related chronic disease in the United States relative to other OECD countries. PMID- 17848461 TI - America's health care safety net: revisiting the 2000 IOM report. AB - The committee that wrote the 2000 Institute of Medicine report on the health care safety net reconvened in 2006 to reflect on the safety net from the perspective of rising numbers of uninsured and underinsured people, the aftermath of Hurricane Katrina, high immigration levels, and new fiscal and policy pressures on care for vulnerable populations. Safety-net providers now participate in Medicaid managed care but find it difficult to meet growing needs for specialty services, particularly mental health care and affordable prescription drugs. How current state reforms and coverage expansions will affect care for the poor and uninsured is a critical issue. PMID- 17848463 TI - Getting the innovation we want. PMID- 17848464 TI - CEA is not a price control. PMID- 17848467 TI - Living will for a handicapped child. PMID- 17848468 TI - Moving toward the exit. PMID- 17848470 TI - Infant mortality in Chile reflects socioeconomic status. PMID- 17848471 TI - Eliminating neglected diseases: impact of published paper. PMID- 17848472 TI - The effect of current cigarette smoking on calf muscle hemoglobin oxygen saturation in patients with intermittent claudication. AB - The purpose of this study was to compare calf muscle hemoglobin oxygen saturation response during exercise between smokers and non-smokers with peripheral arterial disease. Patients limited by intermittent claudication who were smokers (n = 12) were compared with those who had not smoked (n = 28) for at least 1 year prior to investigation. Ankle/brachial index (ABI) measurements were obtained with Doppler ultrasound, and maximal calf blood flow was measured by venous occlusion plethysmography. Hemoglobin oxygen saturation (StO2) of the calf muscle, initial claudication distance (ICD), and absolute claudication distance (ACD) were obtained during a graded treadmill test. Smokers refrained from smoking on the morning of the test. Smokers had similar ABI values compared with non-smokers (0.70 +/- 0.26 vs 0.73 +/- 0.23 [mean +/- SD]; p = 0.808), whereas the smokers had lower values for maximal calf blood flow (8.71 +/- 5.76 %/min vs 11.48 +/- 4.46 %/min; p = 0.038), ICD (122 +/- 123 m vs 243 +/- 177 m; p = 0.023), and ACD (284 +/- 170 m vs 452 +/- 263 m; p = 0.023). Additionally, smokers had lower calf muscle StO2 values at the end of 1 minute (16 +/- 15% vs 37 +/- 19%; p = 0.002) and 2 minutes of exercise (16 +/- 16% vs 35 +/- 25%; p = 0.008), and at the occurrence of ICD (17 +/- 17% vs 32 +/- 23%; p = 0.033) and ACD (16 +/- 16% vs 32 +/- 24%; p = 0.024). After adjusting for blood flow, calf muscle StO2 values remained lower in the smokers (p < 0.05). Finally, calf muscle StO2 at the end of the first minute of exercise was related to ICD (r = 0.611, p < 0.001) and ACD (r = 0.443, p < 0.01). In conclusion, smokers limited by intermittent claudication have lower calf muscle StO2 during exercise than nonsmokers, and lower StO2 during exercise is associated with shorter ICD and ACD. PMID- 17848473 TI - Should troponin and creatinine kinase be routinely measured after vascular surgery? AB - The current guidelines for the evaluation and prediction of adverse cardiovascular events (CVEs) following vascular surgery in high-risk patients recommends serial electrocardiograms (ECGs) but not biomarkers such as cTn-I and CK-MB. The objective of this study was to determine whether biomarkers should be routinely measured in high-risk patients undergoing vascular surgery. A multicenter, prospective study with investigators blinded to core laboratory results was conducted. cTn-I and CK-MB were obtained on the day of surgery, as well as 24 hours, 72 hours and 120 hours after surgery, 24 hours prior to planned hospital discharge and at the onset of symptoms of a suspected CVE. The CVE was adjudicated by an endpoint committee using ECG, biomarker and symptoms data and was defined as cardiac death or myocardial infarction (MI) occurring up to 30 days after surgery. A total of 784 patients, with a mean age of 70.1 (SD +/- 9.8), underwent vascular surgery. Of the 83 patients with a CVE, cTn-I was positive in 42 and CK-MB was positive in 29 on or before the day of the CVE. The number of patients not classified as having a CVE but positive for elevation of cTn-I or CK-MB was 64 and 20, respectively. cTn-I was more sensitive than CK-MB (50.6% versus 34.9%) for predicting a CVE. The optimum time for measuring cTn-I after surgery with the highest positive predictive value was 24 hours. In conclusion, these data support routine serial measurement of cTn-I after vascular surgery. PMID- 17848474 TI - The influence of obesity on arterial compliance in adult men and women. AB - The objective of this study was to determine whether differences in large and small arterial compliance existed among normal weight, overweight, and obese older men and women, and whether large and small arterial compliance were associated with abdominal, hip, and subcutaneous fat distribution. A total of 134 individuals who were 40 years of age and older (age = 62 +/- 11 years; mean +/- SD) were grouped into normal weight (BMI: 18.5-24.9 kg/m2; n = 33), overweight (BMI: 25.0-29.9 kg/m2; n = 48), or obese (BMI: > or =30.0 kg/m2; n = 53) categories. The hemodynamic and arterial compliance measurements were obtained using the HDI/PulseWave CR-2000 CardioVascular Profiling System (Hypertension Diagnostics, Inc). Body mass index, nine-site sum of skinfolds, and circumference measures around the hip and waist were used for analysis. Large and small arterial compliance was lower (p < 0.001) in the obese group (12.4 +/- 4.8 ml/mmHg x 10 vs 4.6 +/- 2.5 ml/mmHg x 100, respectively) than the normal weight (16.2 +/- 4.9 ml/mmHg x 10 vs 5.5 +/- 2.7 ml/mmHg x 100) and overweight (15.2 +/- 4.3 ml/mmHg x 10 vs 5.0 +/- 2.2 ml/mmHg x 100) groups. This difference remained (p < 0.001) after adjusting for body surface area, sex, hyperlipidemia, and hypertension. Additionally, large arterial compliance correlated (p < 0.05) with sum of skinfolds (r = - 0.209), while small arterial compliance correlated with hip circumference (r = - 0.189). Arterial compliance measures were not related (p > 0.05) to waist circumference or waist-to-hip ratio. In conclusion, obesity was associated with a decrease in large and small arterial compliance independent of conventional risk factors. Additionally, subcutaneous fat and fat around the hips were inversely related to arterial compliance. PMID- 17848475 TI - Indices of cardiovascular function derived from peripheral pulse wave analysis using radial applanation tonometry: a measurement repeatability study. AB - Pulse wave analysis (PWA) using applanation tonometry is a non-invasive technique for assessing cardiovascular function. It produces three important indices: ejection duration index (ED%), augmentation index adjusted for heart rate (AIX@75), and subendocardial viability ratio (SEVR%). The aim of this study was to assess within- and between-observer repeatability of these measurements. After resting supine for 15 minutes, 20 ambulant patients (16 male) in sinus rhythm underwent four PWA measurements on a single occasion. Two nurses (A & B) independently and alternately undertook PWA measurements using the same equipment (Omron HEM-757; SphygmoCor with Millar hand-held tonometer) blind to the other nurse's PWA measurements. Within- and between-observer differences were analysed using the Bland-Altman ;limits of agreement' approach (mean difference +/- 2 standard deviations, 2SD). Mean age was 56 (blood pressure, BP 136/79; pulse rate 64). BP/PWA measurements remained stable during assessment. Based on the average of two PWA measurements the mean +/- 2SD between-observer difference in ED% was 0.3 +/- 2.0; AIX@75 1.0 +/- 3.9; and SEVR% 1.7 +/- 14.2. Based on a single PWA measurement the between-observer difference was ED% 0.3 +/- 3.3; AIX@75 1.7 +/- 6.9; and SEVR% 0.6 +/- 22.6. Within-observer differences for nurse-A were ED% 0.0 +/- 5.4; AIX@75 1.5 +/- 7.0; and SEVR% 1.7 +/- 39.0 (nurse-B: 0.1 +/- 3.8; 0.1 +/ 8.0; and 0.6 +/- 23.3, respectively). PWA demonstrates high levels of repeatability even when used by relatively inexperienced staff and has the potential to be included in the routine cardiovascular assessment of ambulant patients. PMID- 17848476 TI - Acute lower limb ischemia as the initial symptom of acute myeloid leukemia. AB - Although coagulatory system disorders are well recognized in patients with acute leukemia, these usually present with either hemorrhagic complications or thrombosis of small vessels. Large vessel thrombosis is a very rare clinical presentation. We present a patient with previously undiagnosed acute myeloid leukemia (M5), who was referred to our hospital with symptoms of acute ischemia of his right lower limb. Occlusion of the right external iliac artery due to a combination of leucostasis and coagulation disorders was noted and successfully treated with urgent leukapheresis, immediate chemotherapy and surgical thromboembolectomy. PMID- 17848477 TI - External iliac artery endofibrosis in an amateur runner: hemodynamic, angiographic, histopathological evaluation and percutaneous revascularization. AB - We describe a case of external iliac artery endofibrosis in an amateur competitive runner. The diagnosis was made by a combination of hemodynamic, angiographic and histopathological assessment and percutaneous revascularization was performed using a balloon expandable stent. PMID- 17848478 TI - A novel approach using atherectomy for chronic total occlusion of the brachial artery: a case report. AB - Chronic upper limb ischemia is uncommon, and is most often secondary to subclavian artery stenosis. Percutaneous intervention for subclavian stenosis usually includes balloon angioplasty and stent implantation. Brachial artery stenosis is even more scarce and accounts for approximately 12% of symptomatic upper extremity ischemia. Because it is rare, the optimal treatment strategy for brachial artery stenosis remains uncertain. We describe a case of chronic brachial artery ischemia due to atherosclerotic disease treated with the SilverHawk plaque excision system and review the available data regarding its use. PMID- 17848479 TI - Peri-operative cardiac biomarker surveillance: a strategy in need of a goal. PMID- 17848483 TI - Current state of endovascular treatment of femoro-popliteal artery disease. AB - Considerable advances have been made over the last decade in percutaneous technology for the treatment of atherosclerotic diseases in the femoro-popliteal arteries. While treatment strategies are well defined in the iliac segment, where angioplasty and stenting perform well in appropriately selected lesions, the search for a durable transcatheter therapy for femoro-popliteal lesions continues. Whereas balloon angioplasty (PTA) is the accepted therapy for short lesions, long diffuse lesions are still recommended for surgical treatment. However, attractive new technologies ranging from transcatheter plaque excision to laser ablation, rotational atherectomy, cryoplasty, brachytherapy, and placement of drug-eluting stents to simple angioplasty with drug-coated balloons may have the potential to replace femoro-popliteal bypass surgery as a treatment of choice for complex lesions. This article reviews the status of percutaneous endovascular techniques for the treatment of femoro-popliteal artery occlusive disease. PMID- 17848484 TI - Controversies in vascular screening art versus science. AB - Whether or not to screen asymptomatic members of the general public for various forms of vascular disease is a controversial issue with huge medical, social, and financial ramifications. This article reviews several criteria for determining the appropriateness of vascular screening, including: (1) is it possible to detect occult vascular disease ;early'?; (2) what should we screen for, and how should we do it?; (3) who should be screened?; and (4) what standards for vascular screening should be set? While some of these controversies may ultimately be resolvable using an evidence-based approach, it is apparent that there are issues which will not be amenable to strict scientific analysis. Individualized approaches to screening will therefore remain the rule for the foreseeable future. PMID- 17848485 TI - Delayed ischemia after subarachnoid hemorrhage: result of vasospasm alone or a broader vasculopathy? AB - The term vasospasm is commonly used to describe constriction of cerebral blood vessels after subarachnoid hemorrhage which results in the restriction of blood flow and ischemia in affected portions of the brain. The pathophysiological changes that underlie vascular constriction after subarachnoid hemorrhage include changes within the vessel walls themselves, alteration of the levels of several vasoactive substances, and broader pathological conditions such as immune responses, inflammation, and oxidative damage. In this review, we summarize the current state of knowledge concerning the processes that occur in cerebral blood vessels after subarachnoid hemorrhage and how they may be involved in the development of vasospasm. We also propose that, rather than merely vasospasm, the multitude of vascular effects occurring after subarachnoid hemorrhage can be best described as a post-subarachnoid hemorrhage vasculopathy. PMID- 17848486 TI - Images in vascular medicine. Nutcracker syndrome. PMID- 17848487 TI - Images in vascular medicine. Unusual etiology of painful leg ulcers. PMID- 17848488 TI - Children in UK emergency departments. PMID- 17848489 TI - Improving parenting: the why and the how. PMID- 17848491 TI - Improving the efficiency of estimation in randomized trials of adaptive treatment strategies. AB - BACKGROUND: Given the history of treatments to date, and the responses of the patient, what is the best treatment to try next? An ensemble of sequential, multistage rules guiding such adaptive decision making can be described as an ;adaptive treatment strategy (ATS)'. Robins' G-computation can be used for estimation of the mean outcome of an ATS from a ;sequential multiple assignment randomized (SMAR)' trial. PURPOSE: To develop a variance estimate for the G computation formula, based on a sequential analysis of the states and treatments observed in the trial, and compare its properties with those of the ;marginal mean' method described by Murphy, which is based on an estimating equation. METHODS: We use both mathematical calculation and simulation studies to demonstrate the properties of the G-computation and its sequential variance estimate, including finite-sample bias and coverage. RESULTS: The sequential method is unbiased and more efficient when the variation in intervening states contributes substantially to the variation in final outcome, and when the study can be designed to guarantee full observation of the ATS under study. The method extends to the comparison of two or more ATS. LIMITATIONS: If full observation cannot be guaranteed, the method may have poor finite-sample properties. CONCLUSIONS: When the states used to adapt treatment contribute substantially to the outcome, and good design technique can be applied, the sequential method provides more efficient estimation. PMID- 17848490 TI - Penicillin-resistant pneumococcus and risk of treatment failure in pneumonia. AB - OBJECTIVE: To determine whether the presence of in vitro penicillin-resistant Streptococcus pneumoniae increases the risk of clinical failure in children hospitalised with severe pneumonia and treated with penicillin/ampicillin. DESIGN: Multicentre, prospective, observational study. SETTING: 12 tertiary-care centres in three countries in Latin America. PATIENTS: 240 children aged 3-59 months, hospitalised with severe pneumonia and known in vitro susceptibility of S pneumoniae. INTERVENTION: Patients were treated with intravenous penicillin/ampicillin after collection of blood and, when possible, pleural fluid for culture. The minimal inhibitory concentration (MIC) test was used to determine penicillin susceptibility of the pneumococcal strains isolated. Children were continuously monitored until discharge. MAIN OUTCOME MEASURES: The primary outcome was treatment failure (using clinical criteria). RESULTS: Overall treatment failure was 21%. After allowing for different potential confounders, there was no evidence of association between treatment failure and in vitro resistance of S pneumoniae to penicillin according to the Clinical Laboratory Standards Institute (CLSI)/National Committee for Clinical Laboratory Standards (NCCLS) interpretative standards ((adj)RR = 1.03; 95%CI: 0.49-1.90 for resistant S pneumoniae). CONCLUSIONS: Intravenous penicillin/ampicillin remains the drug of choice for treating penicillin-resistant pneumococcal pneumonia in areas where the MIC does not exceed 2 microg/ml. PMID- 17848492 TI - An examination of the efficiency of the sequential parallel design in psychiatric clinical trials. AB - BACKGROUND: Psychiatric clinical trials have a high failure rate, even among agents which are known to be effective. Because of this high failure rate, a novel clinical trial design has been proposed which incorporates a second phase in which non-responders to placebo are randomly reassigned to drug or placebo. PURPOSE: The purpose of this research is to examine the efficiency of this new design compared to the conventional two arm clinical trial. We consider both binary and continuous endpoints. METHODS: The limiting distribution of a class of weighted average test statistics is obtained for the binary case which allows analytic calculation of the power for a given set of parameters. For the continuous case, we examine the efficiency of seemingly unrelated regression and a weighted average statistic via simulation. RESULTS: The novel design reduces the sample size 20-25% compared to the standard design under a wide range of parameters. LIMITATIONS: There are no actual trials with the novel design therefore assumptions of the effect size across two periods for actual psychiatric agents is unknown. CONCLUSIONS: The new design reduces sample size which in turn should reduce the cost of clinical trials. Further refinements of the design are possible including alternative test statistics and incorporation of additional data from placebo responders. PMID- 17848493 TI - Estimation of treatment effect adjusting for dependent censoring using the IPCW method: an application to a large primary prevention study for coronary events (MEGA study). AB - BACKGROUND: The MEGA study is a randomized controlled trial conducted in Japan to evaluate the primary preventive effect of pravastatin against coronary heart disease (CHD), in which 8214 subjects are randomized to diet or diet plus pravastatin. Pravastatin reduces the incidence of CHD (hazard ratio=0.67; 95%CI: 0.49-0.91). In the MEGA study, in addition to the usual loss to follow-up cases, there is another problem of drop-outs due to the refusal of further follow-up at 5 years. PURPOSE: To estimate the treatment effect adjusting for some types of dependent censorings observed in the MEGA study and to assess the sensitivity of standard analysis results for these censoring cases. METHODS: The proposed method is a straightforward extension of the inverse probability of censoring weighted (IPCW) method for settings with more than one reason for censoring, where the propensities for drop-outs are modeled separately for each reason. Simulation studies are also conducted to compare the properties of the IPCW estimate with the standard analysis assuming independent censorings. RESULTS: Simulation studies show that the IPCW estimate can correct for selection bias due to dependent censoring that can be explained by measured factors, while the standard analysis is biased. Applying the proposed method to the MEGA study data, several prognostic factors are associated with the censoring processes, and after adjusting for these dependent censorings, slightly larger treatment effects for pravastatin are observed for both CHD (primary endpoint) and stroke (secondary endpoint) events. LIMITATIONS: The method developed is based on the fundamental assumption of sequentially ignorable censoring. CONCLUSIONS: Our proposed method provides a valuable approach for estimating treatment effect adjusting for several types of dependent censorings. Dependent censorings observed in the MEGA study did not cause a severe selection bias attributable to the covariates and the results from the standard analysis were robust in relation to the censorings. PMID- 17848494 TI - Applying the law of iterated logarithm to control type I error in cumulative meta analysis of binary outcomes. AB - BACKGROUND: Cumulative meta-analysis typically involves performing an updated meta-analysis every time when new trials are added to a series of similar trials, which by definition involves multiple inspections. Neither the commonly used random effects model nor the conventional group sequential method can control the type I error for many practical situations. In our previous research, Lan et al. (Lan KKG, Hu M-X, Cappelleri JC. Applying the law of iterated logarithm to cumulative meta-analysis of a continuous endpoint. Statistica Sinica 2003; 13: 1135-45) proposed an approach based on the law of iterated logarithm (LIL) to this problem for the continuous case. PURPOSE: The study is an extension and generalization of our previous research to binary outcomes. Although it is based on the same LIL principle, we found the discrete case much more complex and the results from the continuous case do not apply to the binary case. The simulation study presented here is also more extensive. METHODS: The LIL based method ;penalizes' the Z-value of the test statistic to account for multiple tests and for the estimation of heterogeneity in treatment effects across studies. It involves an adjustment factor, which is directly related to the control of type I error and determined through extensive simulations under various conditions. RESULTS: With an adjustment factor of 2, the LIL-based test statistics controls the overall type I error when odds ratio or relative risk is the parameter of interest. For risk difference, the adjustment factor can be reduced to 1.5. More inspections may require a larger adjustment factor, but the required adjustment factor stabilizes after 25 inspections. LIMITATIONS: It will be ideal if the adjustment factor can be obtained theoretically through a statistical model. Unfortunately, real life data are too complex and we have to solve the problem through simulation. However, for large number of inspections, the adjustment factor will have a limited effect and the type I error is controlled mainly by the LIL. CONCLUSIONS: The LIL method controls the overall type I error for a very broad range of practical situations with a binary outcome, and the LIL works properly in controlling the type I error rates as the number of inspections becomes large. PMID- 17848495 TI - Noncompliance in cancer screening trials. AB - BACKGROUND: Randomized trials evaluating new cancer screening technologies may underestimate the efficacy of screening to reduce cancer mortality if study participants are noncompliant. Participants may fail to comply with the screening itself or fail to obtain appropriate diagnostic follow-up and treatment. Noncompliance with screening has drawn wide attention, but little attention has been paid to noncompliance with diagnostic follow-up and treatment. PURPOSE: To examine the importance of noncompliance with screening, follow-up, and treatment in cancer screening trials. METHODS: The unique problems associated with noncompliance in screening trials are described and provide an example illustrating the potential impact of noncompliance in a screening trial. I discuss issues that arise with measurement of follow-up and therapeutic noncompliance, and the benefit of collecting information on health system and participant characteristics associated with noncompliance. RESULTS: The estimate of the efficacy of a screening program on cancer mortality can be adjusted for screening, follow-up, and treatment noncompliance. Noncompliance needs to be measured in a rigorous, systematic manner across all arms of the trial. Information on health system and participant characteristics associated with compliance may also be incorporated into statistical models to estimate screening effects with full compliance, plan interventions to increase compliance, and extrapolate results of screening trials from one population to another. LIMITATIONS: Measuring compliance with follow-up and treatment can be difficult when these occur outside the trial, and when there is variation among providers in follow-up and treatment practices. CONCLUSIONS: Noncompliance may alter the estimate of a screening effect on cancer mortality in clinical trials. It is possible to adjust screening efficacy estimates for noncompliance using existing statistical techniques. It is important that data describing compliance with screening, follow-up, and treatment are collected as part of standard data collection in cancer screening trials. PMID- 17848496 TI - The intention-to-treat approach in randomized controlled trials: are authors saying what they do and doing what they say? AB - BACKGROUND: Intention-to-treat (ITT) is an approach to the analysis of randomized controlled trials (RCT) in which patients are analyzed as randomized regardless of the treatment actually received. PURPOSE: To ascertain the proportion of RCT reporting the use of intention-to-treat and the accuracy of that report and to examine the distribution and analysis of missing data for the studies reporting an ITT analysis. METHOD: We conducted a cross-sectional literature review of RCTs reported in 10 medical journals in 2002. All articles were assessed using a standardized form. Two evaluators independently reviewed a 10% sample of articles to assess reliability. Subsequently, one evaluator reviewed the remaining articles. The proportion of articles reporting the use of ITT was calculated. Among these, the proportion of articles that ;analyzed patients as randomized' and the proportion and analysis of missing data were evaluated using standardized definitions. RESULTS: Of the 403 articles, 249 (62%) reported the use of ITT. Among these, available patients were clearly analyzed as randomized in 192 (77%). Authors used a modified ITT in 23 (9%); clearly violated a major component of ITT in 17 (7%), and the approach used was unclear in 17 (7%). More than 60% of articles had missing data in their primary analysis. Few articles reported a strategy for missing data. The main reason for missing data was loss to follow up. LIMITATIONS: A single evaluator evaluated most articles, but the high concordance obtained during the inter-rater evaluation suggests that the assessments were consistent. In addition, the small spectrum of journals limits generalizability. Finally, there could be a difference between what was reported and what was performed. CONCLUSIONS: This study emphasizes that authors use the label ;intention-to-treat' quite differently. The most common use refers to the analysis of all available subjects as randomized regardless of the missing data aspect. PMID- 17848497 TI - Design of the fish oil inhibition of stenosis in hemodialysis grafts (FISH) study. AB - BACKGROUND: Arteriovenous grafts (AVG) are the predominant form of permanent vascular access used among hemodialysis (HD) patients in North America but suffer from high intervention and complication rates associated with vascular stenosis. The fish oil inhibition of stenosis in hemodialysis grafts (FISH) study evaluates the efficacy of fish oil in improving HD graft patency. METHODS: This study is a multi-center, randomized, double blind placebo-controlled clinical trial of 232 chronic HD patients who require a new graft access. Participants are randomized to fish oil versus placebo post-operatively. The primary endpoint is the proportion of AVG with loss of native patency within 12 months of creation. Secondary endpoints are aimed to determine the effect of fish oil on factors that may promote stenosis and thrombosis. Cumulative patency rates, survival analysis, and analysis of inflammatory markers and adverse events will provide a better understanding of the potential effect of fish oil on a patient's vascular access and cardiovascular system. The FISH study is registered at current controlled trials (www.controlled-trials.com) ISRCTN: 15838383. RESULTS: Details of the study protocol are described including mechanisms of reducing bias through randomization and double blinding, sample size determination, evaluation of patient adherence, access monitoring, and the safety of using fish oil. The main challenges of designing and implementing this study, including using a natural supplement as an intervention in modern medical practice and recruitment of graft recipients in the ;fistula first' environment are discussed. CONCLUSION: This is the first large, multicenter, randomized controlled trial of a natural supplement in preventing HD graft stenosis and thrombosis. PMID- 17848500 TI - Alpha3-integrins are required for hippocampal long-term potentiation and working memory. AB - Integrins comprise a large family of heterodimeric, transmembrane cell adhesion receptors that mediate diverse neuronal functions in the developing and adult CNS. Recent pharmacological and genetic studies have suggested that beta1 integrins are critical in synaptic plasticity and memory formation. To further define the role of integrins in these processes, we generated a postnatal forebrain and excitatory neuron-specific knockout of alpha3-integrin, one of several binding partners for beta1 subunit. At hippocampal Schaffer collateral CA1 synapses, deletion of alpha3-integrin resulted in impaired long-term potentiation (LTP). Basal synaptic transmission and paired-pulse facilitation were normal in the absence of alpha3-integrin. Behavioral studies demonstrated that the mutant mice were selectively defective in a hippocampus-dependent, nonmatch-to-place working memory task, but were normal in other hippocampus dependent spatial tasks. The impairment in LTP and working memory is similar to that observed in beta1-integrin conditional knockout mice, suggesting that alpha3 integrin is the functional binding partner for beta1 for these processes in the forebrain. PMID- 17848501 TI - Differential effects of muscarinic receptor blockade in prelimbic cortex on acquisition and memory formation of an odor-reward task. AB - The present experiments determined the consequences of blocking muscarinic cholinergic receptors of the prelimbic (PL) cortex in the acquisition and retention of an odor-reward associative task. Rats underwent a training test (five trials) and a 24-h retention test (two retention trials and two relearning trials). In the first experiment, rats were bilaterally infused with scopolamine (20 or 5 microg/site) prior to training. Although scopolamine rats showed acquisition equivalent to PBS-injected controls, they exhibited weakened performance in the 24-h retention test measured by number of errors. In the second experiment, rats were injected with scopolamine (20 microg/site) immediately or 1 h after training and tested 24 h later. Scopolamine rats injected immediately showed severe amnesia detected in two performance measures (errors and latencies), demonstrating deficits in retention and relearning, whereas those injected 1 h later showed good 24-h test performance, similar to controls. These results suggest that muscarinic transmission in the PL cortex is essential for early memory formation, but not for acquisition, of a rapidly learned odor discrimination task. Findings corroborate the role of acetylcholine in consolidation processes and the participation of muscarinic receptors in olfactory associative tasks. PMID- 17848502 TI - Overcoming interference: an fMRI investigation of pattern separation in the medial temporal lobe. AB - The medial temporal lobe (MTL) supports the formation and retrieval of long-term declarative memories, or memories for facts and everyday events. One challenge posed for this type of memory stems from the highly overlapping nature of common episodes. Within cognitive psychology, it is widely accepted that interference between information learned at different times is a major limitation on memory. In spite of several decades of intense research in the fields of interference theory and the neurobiological underpinnings of declarative memory, there is little direct evidence bearing on how the MTL resolves this interference to form accurate memories of everyday facts and events. Computational models of MTL function have proposed a mechanism in which the MTL, specifically the hippocampus, performs pattern separation, whereby overlapping representations are made less similar. However, there is little evidence bearing on how this process is carried out in the intact human MTL. Using high-resolution fMRI, we conducted a set of experiments that taxed behavioral pattern separation by using highly similar, interfering stimuli in a modified continuous recognition task. Regions within the parahippocampal gyrus demonstrated activity consistent with a "recall to reject" strategy. In contrast and critical to performing the task, activity within the hippocampus distinguished between correctly identified true stimulus repetitions, correctly rejected presentations of similar lure stimuli, and false alarms to similar lures. These data support the computational models' assertion that the hippocampus plays a key role in pattern separation. PMID- 17848503 TI - The central nucleus of the amygdala is essential for acquiring and expressing conditional fear after overtraining. AB - The basolateral complex of the amygdala (BLA) is critical for the acquisition and expression of Pavlovian fear conditioning in rats. Nonetheless, rats with neurotoxic BLA lesions can acquire conditional fear after overtraining (75 trials). The capacity of rats with BLA lesions to acquire fear memory may be mediated by the central nucleus of the amygdala (CEA). To examine this issue, we examined the influence of neurotoxic CEA lesions or reversible inactivation of the CEA on the acquisition and expression of conditional freezing after overtraining in rats. Rats with pretraining CEA lesions (whether alone or in combination with BLA lesions) did not acquire conditional freezing to either the conditioning context or an auditory conditional stimulus after extensive overtraining. Similarly, post-training lesions of the CEA or BLA prevented the expression of overtrained fear. Lastly, muscimol infusions into the CEA prevented both the acquisition and the expression of overtrained fear, demonstrating that the effects of CEA lesions are not likely due to the destruction of en passant axons. These results suggest that the CEA is essential for conditional freezing after Pavlovian fear conditioning. Moreover, overtraining may engage a compensatory fear conditioning circuit involving the CEA in animals with damage to the BLA. PMID- 17848504 TI - Postnatal hydrocortisone treatment for chronic lung disease in the preterm newborn and long-term neurodevelopmental follow-up. AB - The benefits versus the risks of postnatal administration of steroids in preterm born infants are still debatable. This review examines the literature on postnatal hydrocortisone treatment for chronic lung disease (CLD) in preterm-born infants with a particular focus on the effects of such treatment on long-term neurodevelopmental outcomes. Quantitative published evidence does not point to a clear advantage of treatment with hydrocortisone over dexamethasone with regard to the impact on long-term neurological outcomes. However, in the absence of a randomised comparison, a consensus may soon have to be reached on the basis of the best available evidence whether hydrocortisone should replace dexamethasone in the treatment of CLD. PMID- 17848505 TI - Neurology of congenital heart disease: insight from brain imaging. PMID- 17848506 TI - Caenorhabditis elegans neuronal regeneration is influenced by life stage, ephrin signaling, and synaptic branching. AB - We previously reported functional regeneration of Caenorhabditis elegans motor neurons after femtosecond laser axotomy. We report here that multiple neuronal types can regrow after laser axotomy using a variety of lasers. The precise pattern of regrowth varies with cell type, stage of animal, and position of axotomy. Mechanosensory axons cut in late larval or adult stages displayed extensive regrowth, yet failed to reach their target area because of guidance errors in the anteroposterior axis. By contrast, mechanosensory axons cut in early larval stages regrew at the same rate but with fewer anteroposterior guidance errors, and were more likely to reach their target area. In adult animals lacking the VAB-1 Eph receptor tyrosine kinase, mechanosensory axon regrowth was more accurate than in the wild type, suggesting that guidance errors of regrowing touch neuron axons are the result of Eph signaling. Kinase-dependent and kinase-independent Eph signaling influenced outgrowth and guidance of regrowing touch neurons, respectively. Mechanosensory neurons regrew when severed proximal to their collateral synaptic branch but did not regrow when severed distal to the branch point. However, the distal axon could regrow if the branch is removed surgically at the same time as distal axotomy, or at a later time. The touch neuron synaptic branch point may act as a sorting area to regulate growth. These findings reveal that multiple influences affect regenerative growth in C. elegans neurons. PMID- 17848507 TI - Visualizing the dynamics of p21(Waf1/Cip1) cyclin-dependent kinase inhibitor expression in living animals. AB - Although the role of p21(Waf1/Cip1) gene expression is well documented in various cell culture studies, its in vivo roles are poorly understood. To gain further insight into the role of p21(Waf1/Cip1) gene expression in vivo, we attempted to visualize the dynamics of p21(Waf1/Cip1) gene expression in living animals. In this study, we established a transgenic mice line (p21-p-luc) expressing the firefly luciferase under the control of the p21(Waf1/Cip1) gene promoter. In conjunction with a noninvasive bioluminescent imaging technique, p21-p-luc mice enabled us to monitor the endogenous p21(Waf1/Cip1) gene expression in vivo. By monitoring and quantifying the p21(Waf1/Cip1) gene expression repeatedly in the same mouse throughout its entire lifespan, we were able to unveil the dynamics of p21(Waf1/Cip1) gene expression in the aging process. We also applied this system to chemically induced skin carcinogenesis and found that the levels of p21(Waf1/Cip1) gene expression rise dramatically in benign skin papillomas, suggesting that p21(Waf1/Cip1) plays a preventative role(s) in skin tumor formation. Surprisingly, moreover, we found that the level of p21(Waf1/Cip1) expression strikingly increased in the hair bulb and oscillated with a 3-week period correlating with hair follicle cycle progression. Notably, this was accompanied by the expression of p63 but not p53. This approach, together with the analysis of p21(Waf1/Cip1) knockout mice, has uncovered a novel role for the p21(Waf1/Cip1) gene in hair development. These data illustrate the unique utility of bioluminescence imaging in advancing our understanding of the timing and, hence, likely roles of specific gene expression in higher eukaryotes. PMID- 17848508 TI - The Rho GTPase-activating proteins RGA-3 and RGA-4 are required to set the initial size of PAR domains in Caenorhabditis elegans one-cell embryos. AB - Caenorhabditis elegans embryos establish cortical domains of PAR proteins of reproducible size before asymmetric cell division. The ways in which the size of these domains is set remain unknown. Here we identify the GTPase-activating proteins (GAPs) RGA-3 and RGA-4, which regulate the activity of the small GTPase RHO-1. rga-3/4(RNAi) embryos have a hypercontractile cortex, and the initial relative size of their anterior and posterior PAR domains is altered. Thus, RHO-1 activity appears to control the level of cortical contractility and concomitantly the size of cortical domains. These data support the idea that in C. elegans embryos the initial size of the PAR domains is set by regulating the contractile activity of the acto-myosin cytoskeleton through the activity of RHO-1. RGA-3/4 have functions different from CYK-4, the other known GAP required for the first cell division, showing that different GAPs cooperate to control the activity of the acto-myosin cytoskeleton in the first cell division of C. elegans embryos. PMID- 17848509 TI - The hypothesis of reproductive compensation and its assumptions about mate preferences and offspring viability. AB - The Compensation Hypothesis says that parents and prospective parents attempt to make up for lowered offspring viability by increasing reproductive effort to produce healthy, competitive offspring and by increasing investment in less viable, but still-living progeny (parental effects). The hypothesis assumes that offspring viability is lower when individuals are constrained (often through sexual conflict) to breed with individuals they do not prefer. We review results of experimental tests of the offspring-viability assumption in Tanzanian cockroaches, fruit flies, pipefish, wild mallards, and feral house mice. Experimental constraints on mating preferences lowered offspring viability in each of the studies. Females breeding under constraints laid more eggs or gave birth to more young than females breeding without or with fewer constraints on their mating preferences, and males mating under constraints on their mate preferences ejaculated more sperm than males mating without constraints. The number of eggs laid or offspring born was higher when female choosers were experimentally constrained to reproduce with males they did not prefer. Constrained females may increase fecundity to enhance the probability that they produce adult offspring with rarer phenotypes with survival benefits against offspring generation pathogens. Similarly, ejaculation of more sperm when males are paired with females they do not prefer may be a mechanism that provides more variable sperm haplotypes for prospective mothers or that may provide nutritional benefits to mothers and zygotes. PMID- 17848510 TI - Human cone photoreceptor dependence on RPE65 isomerase. AB - The visual (retinoid) cycle, the enzymatic pathway that regenerates chromophore after light absorption, is located primarily in the retinal pigment epithelium (RPE) and is essential for rod photoreceptor survival. Whether this pathway also is essential for cone photoreceptor survival is unknown, and there are no data from man or monkey to address this question. The visual cycle is naturally disrupted in humans with Leber congenital amaurosis (LCA), which is caused by mutations in RPE65, the gene that encodes the retinoid isomerase. We investigated such patients over a wide age range (3-52 years) for effects on the cone-rich human fovea. In vivo microscopy of the fovea showed that, even at the youngest ages, patients with RPE65-LCA exhibited cone photoreceptor loss. This loss was incomplete, however, and residual cone photoreceptor structure and function persisted for decades. Basic questions about localization of RPE65 and isomerase activity in the primate eye were addressed by examining normal macaque. RPE65 was definitively localized by immunocytochemistry to the central RPE and, by immunoblotting, appeared to concentrate in the central retina. The central retinal RPE layer also showed a 4-fold higher retinoid isomerase activity than more peripheral RPE. Early cone photoreceptor losses in RPE65-LCA suggest that robust RPE65-based visual chromophore production is important for cones; the residual retained cone structure and function support the speculation that alternative pathways are critical for cone photoreceptor survival. PMID- 17848511 TI - DNA evidence for historic population size and past ecosystem impacts of gray whales. AB - Ecosystem restoration may require returning threatened populations of ecologically pivotal species to near their former abundances, but it is often difficult to estimate historic population size of species that have been heavily exploited. Eastern Pacific gray whales play a key ecological role in their Arctic feeding grounds and are widely thought to have returned to their prewhaling abundance. Recent mortality spikes might signal that the population has reached long-term carrying capacity, but an alternative is that this decline was due to shifting climatic conditions on Arctic feeding grounds. We used a genetic approach to estimate prewhaling abundance of gray whales and report DNA variability at 10 loci that is typical of a population of approximately 76,000 118,000 individuals, approximately three to five times more numerous than today's average census size of 22,000. Coalescent simulations indicate these estimates may include the entire Pacific metapopulation, suggesting that our average measurement of approximately 96,000 individuals was probably distributed between the eastern and currently endangered western Pacific populations. These levels of genetic variation suggest the eastern population is at most at 28-56% of its historical abundance and should be considered depleted. If used to inform management, this would halve acceptable human-caused mortality for this population from 417 to 208 per year. Potentially profound ecosystem impacts may have resulted from a decline from 96,000 gray whales to the current population. At previous levels, gray whales may have seasonally resuspended 700 million cubic meters of sediment, as much as 12 Yukon Rivers, and provided food to a million sea birds. PMID- 17848512 TI - Structural basis for evasion of IgA immunity by Staphylococcus aureus revealed in the complex of SSL7 with Fc of human IgA1. AB - Infection by Staphylococcus aureus can result in severe conditions such as septicemia, toxic shock, pneumonia, and endocarditis with antibiotic resistance and persistent nasal carriage in normal individuals being key drivers of the medical impact of this virulent pathogen. In both virulent infection and nasal colonization, S. aureus encounters the host immune system and produces a wide array of factors that frustrate host immunity. One in particular, the prototypical staphylococcal superantigen-like protein SSL7, potently binds IgA and C5, thereby inhibiting immune responses dependent on these major immune mediators. We report here the three-dimensional structure of the complex of SSL7 with Fc of human IgA1 at 3.2 A resolution. Two SSL7 molecules interact with the Fc (one per heavy chain) primarily at the junction between the Calpha2 and Calpha3 domains. The binding site on each IgA chain is extensive, with SSL7 shielding most of the lateral surface of the Calpha3 domain. However, the SSL7 molecules are positioned such that they should allow binding to secretory IgA. The key IgA residues interacting with SSL7 are also bound by the leukocyte IgA receptor, FcalphaRI (CD89), thereby explaining how SSL7 potently inhibits IgA dependent cellular effector functions mediated by FcalphaRI, such as phagocytosis, degranulation, and respiratory burst. Thus, the ability of S. aureus to subvert IgA-mediated immunity is likely to facilitate survival in mucosal environments such as the nasal passage and may contribute to systemic infections. PMID- 17848513 TI - MicroRNA regulation of cyclooxygenase-2 during embryo implantation. AB - The implantation process is complex, requiring reciprocal interactions between implantation-competent blastocysts and the receptive uterus. Because microRNAs (miRNAs) have major roles in regulating gene expression, we speculated that they participate in directing the highly regulated spatiotemporally expressed genetic network during implantation. Here, we show that two miRNAs, mmu-miR-101a and mmu miR-199a*, are spatiotemporally expressed in the mouse uterus during implantation coincident with expression of cyclooxygenase-2, a gene critical for implantation. More interestingly, our in vitro gain- and loss-of-function experiments show that cyclooxygenase-2 expression is posttranscriptionally regulated by these two miRNAs. We report on miRNA-mediated regulation of uterine gene expression in the context of implantation. We believe that many other critical genes related to this process are also regulated by miRNAs. Thus, elucidating the physiological roles of uterine miRNAs will help us better understand the genetic control of implantation, the gateway to a successful pregnancy. PMID- 17848514 TI - Structural insights into the Slit-Robo complex. AB - Slits are large multidomain leucine-rich repeat (LRR)-containing proteins that provide crucial guidance cues in neuronal and vascular development. More recently, Slits have been implicated in heart morphogenesis, angiogenesis, and tumor metastasis. Slits are ligands for the Robo (Roundabout) receptors, which belong to the Ig superfamily of transmembrane signaling molecules. The Slit-Robo interaction is mediated by the second LRR domain of Slit and the two N-terminal Ig domains of Robo, but the molecular details of this interaction and how it induces signaling remain unclear. Here we describe the crystal structures of the second LRR domain of human Slit2 (Slit2 D2), the first two Ig domains of its receptor Robo1 (Ig1-2), and the minimal complex between these proteins (Slit2 D2 Robo1 Ig1). Slit2 D2 binds with its concave surface to the side of Ig1 with electrostatic and hydrophobic contact regions mediated by residues that are conserved in other family members. Surface plasmon resonance experiments and a mutational analysis of the interface confirm that Ig1 is the primary domain for binding Slit2. These structures provide molecular insight into Slit-Robo complex formation and will be important for the development of novel cancer therapeutics. PMID- 17848515 TI - Biosynthesis of 2-methylbacteriohopanepolyols by an anoxygenic phototroph. AB - Sedimentary 2-methyhopanes have been used as biomarker proxies for cyanobacteria, the only known bacterial clade capable of oxygenic photosynthesis and the only group of organisms found thus far to produce abundant 2 methylbacteriohopanepolyols (2-MeBHPs). Here, we report the identification of significant quantities of 2-MeBHP in two strains of the anoxygenic phototroph Rhodopseudomonas palustris. Biosynthesis of 2-MeBHP can occur in the absence of O(2), deriving the C-2 methyl group from methionine. The relative abundance of 2 MeBHP varies considerably with culture conditions, ranging from 13.3% of total bacteriohopanepolyol (BHP) to trace levels of methylation. Analysis of intact BHPs reveals the presence of methylated bacteriohopane-32,33,34,35-tetrol but no detectable methylation of 35-aminobacteriohopane-32,33,34-triol. Our results demonstrate that an anoxygenic photoautotroph is capable of generating 2-MeBHPs and show that the potential origins of sedimentary 2-methylhopanoids are more diverse than previously thought. PMID- 17848516 TI - Maintenance of imprinting and nuclear architecture in cycling cells. AB - Dynamic gene repositioning has emerged as an additional level of epigenetic gene regulation. An early example was the report of a transient, spatial convergence (< or =2 microm) of oppositely imprinted regions ("kissing"), including the Angelman syndrome/Prader-Willi syndrome (AS/PWS) locus and the Beckwith-Wiedemann syndrome locus in human lymphocytes during late S phase. It was argued that kissing is required for maintaining opposite imprints in cycling cells. Employing 3D-FISH with a BAC contig covering the AS/PWS region, light optical, serial sectioning, and quantitative 3D-image analysis, we observed that both loci always retained a compact structure and did not form giant loops. Three-dimensional distances measured among various, homologous AS/PWS segments in 393 human lymphocytes, 132 human fibroblasts, and 129 lymphoblastoid cells from Gorilla gorilla revealed a wide range of distances at any stage of interphase and in G(0). At late S phase, 4% of nuclei showed distances < or =2 microm, 49% showed distances >6 microm, and 18% even showed distances >8 microm. A similar distance variability was found for Homo sapiens (HSA) 15 centromeres in a PWS patient with a deletion of the maternal AS/PWS locus and for the Beckwith-Wiedemann syndrome loci in human lymphocytes. A transient kiss during late S phase between loci widely separated at other stages of the cell cycle seems incompatible with known global constraints of chromatin movements in cycling cells. Further experiments suggest that the previously observed convergence of AS/PWS loci during late S phase was most likely a side effect of the convergence of nucleolus organizer region-bearing acrocentric human chromosomes, including HSA 15. PMID- 17848517 TI - Dual-specificity splice sites function alternatively as 5' and 3' splice sites. AB - As a result of large-scale sequencing projects and recent splicing-microarray studies, estimates of mammalian genes expressing multiple transcripts continue to increase. This expansion of transcript information makes it possible to better characterize alternative splicing events and gain insights into splicing mechanisms and regulation. Here, we describe a class of splice sites that we call dual-specificity splice sites, which we identified through genome-wide, high quality alignment of mRNA/EST and genome sequences and experimentally verified by RT-PCR. These splice sites can be alternatively recognized as either 5' or 3' splice sites, and the dual splicing is conceptually similar to a pair of mutually exclusive exons separated by a zero-length intron. The dual-splice-site sequences are essentially a composite of canonical 5' and 3' splice-site consensus sequences, with a CAG|GURAG core. The relative use of a dual site as a 5' or 3' splice site can be accurately predicted by assuming competition for specific binding between spliceosomal components involved in recognition of 5' and 3' splice sites, respectively. Dual-specificity splice sites exist in human and mouse, and possibly in other vertebrate species, although most sites are not conserved, suggesting that their origin is recent. We discuss the implications of this unusual splicing pattern for the diverse mechanisms of exon recognition and for gene evolution. PMID- 17848518 TI - Proteasomal selection of multiprotein complexes recruited by LIM homeodomain transcription factors. AB - Complexes composed of multiple proteins regulate most cellular functions. However, our knowledge about the molecular mechanisms governing the assembly and dynamics of these complexes in cells remains limited. The in vivo activity of LIM homeodomain (LIM-HD) proteins, a class of transcription factors that regulates neuronal development, depends on the high-affinity association of their LIM domains with cofactor of LIM homeodomain proteins (LIM-HDs) (CLIM, also known as Ldb or NLI). CLIM cofactors recruit single-stranded DNA-binding protein 1 (SSDP1, also known as SSBP3), and this interaction is important for the activation of the LIM-HD/CLIM protein complex in vivo. Here, we identify a cascade of specific protein interactions that protect LIM-HD multiprotein complexes from proteasomal degradation. In this cascade, CLIM stabilizes LIM-HDs, and SSDP1 stabilizes CLIM. Furthermore, we show that stabilizing cofactors prevent binding of ubiquitin ligases to multiple protein interaction domains in LIM-HD recruited protein complexes. Together, our results indicate a combinatorial code that selects specific multiprotein complexes via proteasomal degradation in cells with broad implications for the assembly and specificity of multiprotein complexes. PMID- 17848519 TI - Oxidative stress causes bone loss in estrogen-deficient mice through enhanced bone marrow dendritic cell activation. AB - Increased production of tumor necrosis factor alpha (TNF) in the bone marrow (BM) in response to both oxidative stress and T cell activation contributes to the bone loss induced by estrogen deficiency, but it is presently unknown whether oxidative stress causes bone loss through T cells. Here we show that ovariectomy causes an accumulation in the BM of reactive oxygen species, which leads to increased production of TNF by activated T cells through up-regulation of the costimulatory molecule CD80 on dendritic cells. Accordingly, bone loss is prevented by treatment of ovariectomized mice with either antioxidants or CTLA4 Ig, an inhibitor of the CD80/CD28 pathway. In summary, reactive oxygen species accumulation in the BM is an upstream consequence of ovariectomy that leads to bone loss by activating T cells through enhanced activity of BM dendritic cells, and these findings suggest that the CD80/CD28 pathway may represent a therapeutic target for postmenopausal bone loss. PMID- 17848520 TI - Nonhuman primate event-related potentials indexing covert shifts of attention. AB - A half-century's worth of research has established the existence of numerous event-related potential components measuring different cognitive operations in humans including the selection of stimuli by covert attention mechanisms. Surprisingly, it is unknown whether nonhuman primates exhibit homologous electrophysiological signatures of selective visual processing while viewing complex scenes. We used an electrophysiological technique with macaque monkeys analogous to procedures for recording scalp event-related potentials from humans and found that monkeys exhibit short-latency visual components sensitive to sensory processing demands and lateralizations related to shifting of covert attention similar to the human N2pc component. These findings begin to bridge the gap between the disparate literatures by using electrophysiological measurements to study the deployment of visual attention in the brains of humans and nonhuman primates. PMID- 17848521 TI - Analysis of ryanodine receptor clusters in rat and human cardiac myocytes. AB - Single rat ventricular myocytes and human ventricle tissue sections were labeled with antibodies against the ryanodine receptor (RyR) and alpha-actinin to examine the 3D distribution of RyRs with confocal microscopy. Image contrast was maximized by refractive index matching and deconvolution. The RyR label formed discrete puncta representing clusters of RyRs or "couplons" around the edges of the myofilaments with a nearest-neighbor spacing of 0.66 +/- 0.06 microm in rat and 0.78 +/- 0.07 microm in human. Each bundle of myofibrils was served by approximately six couplons, which supplied a cross-sectional area of approximately 0.6 microm(2) in rat and approximately 0.8 microm(2) in human. Although the couplons were in reasonable registration with z-lines, there were discontinuities in the longitudinal position of sarcomeres so that dislocations in the order of RyR clusters occurred. There was approximately 53% longitudinal registration of RyR clusters, suggesting a nonrandom placement of couplons around the sarcomere. These data can explain the spherical propagation of Ca(2+) waves and provide quantitative 3D data sets needed for accurate modeling of cardiac Ca(2+)-induced Ca(2+) release. By quantifying labeling intensity in rat ventricular myocytes, a lower limit of 78 RyRs per cluster (on average) was obtained. By modeling the couplon as a disk wrapping around a t-tubule and fitting cluster images, 95% of couplons contained between 120 and 260 RyRs (assuming that RyRs are tight packed with a spacing of 29 nm). Assuming similar labeling efficiency in human, from the fluorescence intensity alone we estimate that human ventricular myocytes contain approximately 30% fewer RyRs per couplon than rat. PMID- 17848522 TI - Myocardial ischemia results in tetrahydrobiopterin (BH4) oxidation with impaired endothelial function ameliorated by BH4. AB - Coronary vasodilation is impaired in the postischemic heart with a loss of endothelial nitric oxide synthase (eNOS) activity, but the mechanisms underlying ischemia-induced eNOS dysfunction are not understood. For nitric oxide (NO) synthesis, eNOS requires the redox-sensitive cofactor tetrahydrobiopterin (BH(4)); however, the role of BH(4) in ischemia-induced endothelial dysfunction remains unknown. Therefore, isolated rat hearts were subjected to varying durations of ischemia, and the alterations in NOS-dependent vasodilation were measured and correlated with assays of eNOS activity and cardiac BH(4) concentrations. Ischemia time-dependently decreased cardiac BH(4) content with 85, 95, or 97% irreversible degradation after 30, 45, or 60 min of ischemia, respectively. Paralleling the decreases in BH(4), reductions of eNOS activity were seen of 58, 86, or 92%, and NOS-derived superoxide production was greatly increased. Addition of 10 microM BH(4) enhanced eNOS activity in nonischemic hearts and partially restored activity after ischemia. It also suppressed NOS derived superoxide production. Impaired coronary flow during postischemic reperfusion was improved by BH(4) infusion. Thus, BH(4) depletion contributes to postischemic eNOS dysfunction, and BH(4) treatment is effective in partial restoration of endothelium-dependent coronary flow. Supplementation of BH(4) may therefore be an important therapeutic approach to reverse endothelial dysfunction in postischemic tissues. PMID- 17848524 TI - Robust protein protein interactions in crowded cellular environments. AB - The capacity of proteins to interact specifically with one another underlies our conceptual understanding of how living systems function. Systems-level study of specificity in protein-protein interactions is complicated by the fact that the cellular environment is crowded and heterogeneous; interaction pairs may exist at low relative concentrations and thus be presented with many more opportunities for promiscuous interactions compared with specific interaction possibilities. Here we address these questions by using a simple computational model that includes specifically designed interacting model proteins immersed in a mixture containing hundreds of different unrelated ones; all of them undergo simulated diffusion and interaction. We find that specific complexes are quite robust to interference from promiscuous interaction partners only in the range of temperatures T(design) > T > T(rand). At T > T(design), specific complexes become unstable, whereas at T < T(rand), formation of specific complexes is suppressed by promiscuous interactions. Specific interactions can form only if T(design) > T(rand). This condition requires an energy gap between binding energy in a specific complex and set of binding energies between randomly associating proteins, providing a general physical constraint on evolutionary selection or design of specific interacting protein interfaces. This work has implications for our understanding of how the protein repertoire functions and evolves within the context of cellular systems. PMID- 17848523 TI - TRRAP and GCN5 are used by c-Myc to activate RNA polymerase III transcription. AB - Activation of RNA polymerase (pol) II transcription by c-Myc generally involves recruitment of histone acetyltransferases and acetylation of histones H3 and H4. Here, we describe the mechanism used by c-Myc to activate pol III transcription of tRNA and 5S rRNA genes. Within 2 h of its induction, c-Myc appears at these genes along with the histone acetyltransferase GCN5 and the cofactor TRRAP. At the same time, occupancy of the pol III-specific factor TFIIIB increases and histone H3 becomes hyperacetylated, but increased histone H4 acetylation is not detected at these genes. The rapid acetylation of histone H3 and promoter assembly of TFIIIB, c-Myc, GCN5, and TRRAP are followed by recruitment of pol III and transcriptional induction. The selective acetylation of histone H3 distinguishes pol III activation by c-Myc from mechanisms observed in other systems. PMID- 17848525 TI - Ribonucleoprotein-masked nicks at 50-kbp intervals in the eukaryotic genomic DNA. AB - By using a microscopic approach, field inversion single-cell gel electrophoresis, we show that preformed single-strand discontinuities are present in the chromatin of resting and proliferating mammalian and yeast cells. These single-strand breaks are primarily nicks positioned at approximately 50-kbp intervals throughout the entire genome that could be efficiently labeled in situ by DNA polymerase I holoenzyme but not by Klenow fragment and terminal transferase unless after ribonucleolytic treatments. The RNA molecules involved appear to comprise R-loops, recognized by the S9.6 RNA/DNA hybrid-specific antibody. By using the breakpoint cluster region of the Mixed Lineage Leukemia (MLL) gene as a model, we have found that the number of manifest nicks detected by FISH performed after field inversion single-cell gel electrophoresis depends on epigenetic context, but the difference between germ-line and translocated MLL alleles is abolished by protease treatment. Our data imply that the double-stranded genomic DNA is composed of contiguous rather than continuous single strands and reveal an aspect of higher-order chromatin organization with ribonucleoprotein-associated persistent nicks defining approximately 50-kbp domains. PMID- 17848526 TI - Correct dosage of Fog2 and Gata4 transcription factors is critical for fetal testis development in mice. AB - Previous reports suggested that humans and mice differ in their sensitivity to the genetic dosage of transcription factors that play a role in early testicular development. This difference implies that testis determination might be somewhat different in these two species. We report that the Fog2 and Gata4 transcription factors are haploinsufficient for testis determination in mice. Whether gonadal sex reversal occurs depends on genetic background (i.e., modifier genes). For example, C57BL/6J (B6) XY mice develop testes if they are heterozygous for a mutant Fog2 (Fog2-) or Gata4 (Gata4(ki)) allele. However, if the B6 Y chromosome (Y(B6)) is replaced by the AKR Y chromosome (Y(AKR)), B6 Fog2-/+ XY(AKR) mice develop ovaries, and B6 Gata4(ki)/+ XY(AKR) mice develop ovaries and ovotestes (gonads containing both ovarian and testicular tissue). Furthermore, DBA/2J (D2) Fog2-/+ XY(AKR) mice and (B6 x D2)F1 hybrid Gata4(ki)/+ XY(AKR) mice develop testes. Sry is expressed in the mutant XY gonads, indicating that the lack of Sry expression is not the cause of ovarian tissue development in B6 Fog2-/+ or Gata4(ki)/+ XY(AKR) mice. However, up-regulation of Sox9 expression, which is critical for normal testicular development, does not occur in mutant XY gonads that develop as ovaries. We conclude that under certain genetic conditions, Sox9 up-regulation depends on the proper dosage of Fog2 and Gata4. We propose that in humans the FOG2 and/or GATA4 genes might be haploinsufficient for normal testis determination and thus could be the cause of some previously unassigned cases of XY gonadal sex reversal. PMID- 17848527 TI - A structural gap in Dpo4 supports mutagenic bypass of a major benzo[a]pyrene dG adduct in DNA through template misalignment. AB - Erroneous replication of lesions in DNA by DNA polymerases leads to elevated mutagenesis. To understand the molecular basis of DNA damage-induced mutagenesis, we have determined the x-ray structures of the Y-family polymerase, Dpo4, in complex with a DNA substrate containing a bulky DNA lesion and incoming nucleotides. The DNA lesion is derived from an environmentally widespread carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BP). The potent carcinogen BP is metabolized to diol epoxides that form covalent adducts with cellular DNA. In the present study, the major BP diol epoxide adduct in DNA, BP N(2)-deoxyguanosine (BP-dG), was placed at a template-primer junction. Three ternary complexes reveal replication blockage, extension past a mismatched lesion, and a -1 frameshift mutation. In the productive structures, the bulky adduct is flipped/looped out of the DNA helix into a structural gap between the little finger and core domains. Sequestering of the hydrophobic BP adduct in this new substrate-binding site permits the DNA to exhibit normal geometry for primer extension. Extrusion of the lesion by template misalignment allows the base 5' to the adduct to serve as the template, resulting in a -1 frameshift. Subsequent strand realignment produces a mismatched base opposite the lesion. These structural observations, in combination with replication and mutagenesis data, suggest a model in which the additional substrate-binding site stabilizes the extrahelical nucleotide for lesion bypass and generation of base substitutions and -1 frameshift mutations. PMID- 17848528 TI - Generalization of distance to higher dimensional objects. AB - The measurement of distance between two objects is generalized to the case where the objects are no longer points but are one-dimensional. Additional concepts such as nonextensibility, curvature constraints, and noncrossing become central to the notion of distance. Analytical and numerical results are given for some specific examples, and applications to biopolymers are discussed. PMID- 17848529 TI - Optical density changes in dry-processed films. AB - CONTEXT: Dry-processed radiographic films should be stored in a temperature controlled environment away from direct light to prevent image deterioration. However, films occasionally are subjected to other conditions, such as when they are left inadvertently on viewing boxes or removed from the radiology department. OBJECTIVE: To assess the effects of heat and light on optical density in radiographic films produced with dry laser imagers. METHODS: Step-wedge images generated by a dry laser imaging system were placed on an illuminated viewing box, inside the trunk of a car and in direct sunlight on a hot day for varying lengths of time. Changes in optical density (OD) then were measured with a densitometer. Changes of more than 2 standard deviations from the original OD were attributed to the effects of light and heat. RESULTS: The films left on a viewing box and inside a car's trunk did not show significant changes in OD. However, films subjected to direct sunlight for 30 minutes or more at an average temperature of 40 degrees C (104 degrees F) showed significant changes in OD in the straight-line portion of the Hurter and Driffield curve. CONCLUSION: Dry processed films can degrade when exposed to temperatures higher than 35 degrees C (95 degrees F) and should be stored properly to avoid affecting their diagnostic quality. PMID- 17848530 TI - Patient dose from CT: a literature review. AB - CONTEXT: Computed tomography (CT) exams are increasingly common and account for a significant portion of individuals' mounting exposure to medical radiation. OBJECTIVE: To explore issues surrounding patient radiation dose, including techniques for minimizing dose and the feasibility of tracking lifetime exposure to medical radiation from CT and other imaging exams. METHODS: The authors conducted a review of the recent literature to assess current knowledge of dose levels, protocols for minimizing patient dose and possible systems for tracking cumulative dose. RESULTS: Currently, no regulations are in place to track cumulative patient radiation dose. However, the authors discuss possible means of recording, tracking and storing this data, such as standardizing its inclusion in DICOM headers and transmitting it to electronic personal health records. CONCLUSION: More research is needed to develop and implement uniform dose tracking procedures and protocols for minimizing patient dose. PMID- 17848531 TI - Paget disease of bone. AB - Paget disease of bone, also known as osteitis deformans, is a nonmalignant disease of bone that causes accelerated and abnormal bone remodeling. It is the second most common bone disorder, osteoporosis being first. It is a localized disorder, meaning it affects just 1 or several bones in the body. Paget disease of bone is characterized by enlarged and deformed bones and occurs mainly in the axial skeleton. The cause of the disease is still not known entirely, but genetics are certain to be involved, and viral factors also are suspected. PMID- 17848532 TI - Spinal curves and scoliosis. AB - Scoliosis, an abnormal side-to-side curve of the spine with associated vertebral rotation, affects as many as 4% of all adolescents. Several different categories of scoliosis exist, and treatment can range from observation and follow-up to bracing and surgical correction. This article discusses special imaging series for scoliosis and emphasizes the need for proper radiation protection techniques for patients with scoliosis, most of whom are girls in their early to mid-teens. PMID- 17848537 TI - Imaging the L5-S1 joint space. PMID- 17848538 TI - Revisiting radiation policies. PMID- 17848540 TI - Contrast media handling. PMID- 17848542 TI - Patient page. Who's taking your X-ray? PMID- 17848541 TI - Radiation dose during barium enema. PMID- 17848543 TI - Seeing and knowing in structural biology. PMID- 17848545 TI - Intestinal monoacylglycerol metabolism: developmental and nutritional regulation of monoacylglycerol lipase and monoacylglycerol acyltransferase. AB - Intestinal monoacylglycerol (MG) metabolism is well known to involve its anabolic reesterification to triacylglycerol (TG). We recently provided evidence for enterocyte MG hydrolysis and demonstrated expression of the monoacylglycerol lipase (MGL) gene in human intestinal Caco-2 cells and rodent small intestinal mucosa. Despite the large quantities of MG derived from dietary TG, the regulation of MG metabolism in the intestine has not been previously explored. In the present studies, we examined the mRNA expression, protein expression, and activities of the two known MG-metabolizing enzymes, MGL and MGAT2, in C57BL/6 mouse small intestine, as well as liver and adipose tissues, during development and under nutritional modifications. Results demonstrate that MG metabolism undergoes tissue-specific changes during development. Marked induction of small intestinal MGAT2 protein expression and activity were found during suckling. Moreover, while substantial levels of MGL protein and activity were detected in adult intestine, its regulation during ontogeny was complex, suggesting post transcriptional regulation of expression. In addition, during the suckling period MG hydrolytic activity is likely to derive from carboxyl ester lipase rather than MGL. In contrast to intestinal MGL, liver MGL mRNA, protein and activity all increased 5-10-fold during development, suggesting that transcriptional regulation is the primary mechanism for hepatic MGL expression. Three weeks of high fat feeding (40% kcal) significantly induced MGL expression and activity in small intestine relative to low fat feeding (10% kcal), but little change was observed upon starvation, suggesting a role for MGL in dietary lipid assimilation following a high fat intake. PMID- 17848544 TI - The slingshot family of phosphatases mediates Rac1 regulation of cofilin phosphorylation, laminin-332 organization, and motility behavior of keratinocytes. AB - The motility of keratinocytes is an essential component of wound closure and the development of epidermal tumors. In vitro, the specific motile behavior of keratinocytes is dictated by the assembly of laminin-332 tracks, a process that is dependent upon alpha6beta4 integrin signaling to Rac1 and the actin-severing protein cofilin. Here we have analyzed how cofilin phosphorylation is regulated by phosphatases (slingshot (SSH) or chronophin (CIN)) downstream of signaling by alpha6beta4 integrin/Rac1 in human keratinocytes. Keratinocytes express all members of the SSH family (SSH1, SSH2, and SSH3) and CIN. However, expression of phosphatase-dead versions of all three SSH proteins, but not dominant inactive CIN, results in phosphorylation/inactivation of cofilin, changes in actin cytoskeleton organization, loss of cell polarity, and assembly of aberrant arrays of laminin-332 in human keratinocytes. SSH activity is regulated by 14-3-3 protein binding, and intriguingly, 14-3-3/alpha6beta4 integrin protein interaction is required for keratinocyte migration. We wondered whether 14-3-3 proteins function as regulators of Rac1-mediated keratinocyte migration patterns. In support of this hypothesis, inhibition of Rac1 results in an increase in 14-3 3 protein association with SSH. Thus, we propose a novel mechanism in which alpha6beta4 integrin signaling via Rac1, 14-3-3 proteins, and SSH family members regulates cofilin activation, cell polarity, and matrix assembly, leading to specific epidermal cell migration behavior. PMID- 17848546 TI - Proteomic and lipid characterization of apolipoprotein B-free luminal lipid droplets from mouse liver microsomes: implications for very low density lipoprotein assembly. AB - The assembly of very low density lipoproteins involves the formation of a primordial, poorly lipidated apoB-containing particle in the endoplasmic reticulum, followed by the addition of neutral lipid from luminal lipid droplets (LLD). However, the lipid and protein compositions of LLD have not been determined. We have isolated LLD from mouse liver microsomes and analyzed their lipid and protein compositions. LLD are variably sized particles relatively poor in triacylglycerol (TG) content when compared with the lipid composition of cytosolic lipid droplets (CLD). They are devoid of apoB, adipophilin, and albumin but contain numerous proteins different from those found on CLD, including TG hydrolase (TGH), carboxylesterase 1 (Ces1), microsomal triglyceride transfer protein (MTP), and apoE. Ectopic expression of TGH in McArdle RH7777 hepatoma cells resulted in decreased cellular TG levels, demonstrating a role for TGH in the mobilization of hepatic neutral lipid stores. The isolation and characterization of LLD provide new supporting evidence for the two-step assembly of very low density lipoproteins. PMID- 17848547 TI - Nucleocytoplasmic shuttling of the zinc finger protein EZI Is mediated by importin-7-dependent nuclear import and CRM1-independent export mechanisms. AB - Nucleocytoplasmic translocation constitutes a foundation for nuclear proteins to exert their proper functions and hence for various biological reactions to occur normally in eukaryotic cells. We reported previously that EZI/Zfp467, a 12 zinc finger motif-containing protein, localizes predominantly in the nucleus, yet the underlying mechanism still remains elusive. Here we constructed a series of mutant forms of EZI and examined their subcellular localization. The results delineated a non-canonical nuclear localization signal in the region covering the 9th to the 12th zinc fingers, which was necessary for nuclear accumulation of EZI as well as sufficient to confer nuclear localizing ability to a heterologous protein. We also found that the N-terminal domain of EZI is necessary for its nuclear export, the process of which was not sensitive to the CRM1 inhibitor leptomycin B. An interaction proteomics approach and the following co immunoprecipitation experiments identified the nuclear import receptor importin-7 as a molecule that associated with EZI and, importantly, short interfering RNA mediated knockdown of importin-7 expression completely abrogated nuclear accumulation of EZI. Taken together, these results identify EZI as a novel cargo protein for importin-7 and demonstrate a nucleocytoplasmic shuttling mechanism that is mediated by importin-7-dependent nuclear localization and CRM1 independent nuclear export. PMID- 17848548 TI - Restricted active site docking by enzyme-bound substrate enforces the ordered cleavage of prothrombin by prothrombinase. AB - The preferred pathway for prothrombin activation by prothrombinase involves initial cleavage at Arg(320) to produce meizothrombin, which is then cleaved at Arg(271) to liberate thrombin. Exosite binding drives substrate affinity and is independent of the bond being cleaved. The pathway for cleavage is determined by large differences in V(max) for cleavage at the two sites within intact prothrombin. By fluorescence binding studies in the absence of catalysis, we have assessed the ability of the individual cleavage sites to engage the active site of Xa within prothrombinase at equilibrium. Using a panel of recombinant cleavage site mutants, we show that in intact prothrombin, the Arg(320) site effectively engages the active site in a 1:1 interaction between substrate and enzyme. In contrast, the Arg(271) site binds to the active site poorly in an interaction that is approximately 600-fold weaker. Perceived substrate affinity is independent of active site engagement by either cleavage site. We further show that prior cleavage at the 320 site or the stabilization of the uncleaved zymogen in a proteinase-like state facilitates efficient docking of Arg(271) at the active site of prothrombinase. Therefore, we establish direct relationships between docking of either cleavage site at the active site of the catalyst, the V(max) for cleavage at that site, substrate conformation, and the resulting pathway for prothrombin cleavage. Exosite tethering of the substrate in either the zymogen or proteinase conformation dictates which cleavage site can engage the active site of the catalyst and enforces the sequential cleavage of prothrombin by prothrombinase. PMID- 17848549 TI - Laser excitation studies of the product release steps in the catalytic cycle of the light-driven enzyme, protochlorophyllide oxidoreductase. AB - The latter stages of the catalytic cycle of the light-driven enzyme, protochlorophyllide oxidoreductase, have been investigated using novel laser photoexcitation methods. The formation of the ternary product complex was initiated with a 6-ns laser pulse, which allowed the product release steps to be kinetically accessed for the first time. Subsequent absorbance changes associated with the release of the NADP+ and chlorophyllide products from the enzyme could be followed on a millisecond timescale. This has facilitated a detailed kinetic and thermodynamic characterization for the interconversion of all the various bound and unbound product species. Initially, NADP+ is released from the enzyme in a biphasic process with rate constants of 1210 and 237 s(-1). The rates of both phases show a significant dependence on the viscosity of the solvent and become considerably slower at higher glycerol concentrations. The fast phase of this process exhibits no dependence on NADP+ concentration, suggesting that conformational changes are required prior to NADP+ release. Following NADP+ release, the NADPH rebinds to the enzyme with a maximum rate constant of approximately 72 s(-1). At elevated temperatures (>298 K) chlorophyllide is released from the enzyme to yield the free product with a maximum rate constant of 20 s(-1). The temperature dependencies of the rates of each of these steps were measured, and enthalpies and entropies of activation were calculated using the Eyring equation. A comprehensive kinetic and thermodynamic scheme for these final stages of the reaction mechanism is presented. PMID- 17848550 TI - The yeast Hex3.Slx8 heterodimer is a ubiquitin ligase stimulated by substrate sumoylation. AB - Hex3 and Slx8 are Saccharomyces cerevisiae proteins with important functions in DNA damage control and maintenance of genomic stability. Both proteins have RING domains at their C termini. Such domains are common in ubiquitin and ubiquitin like protein ligases (E3s), but little was known about the molecular functions of either protein. In this study we identified HEX3 as a high-copy suppressor of a temperature-sensitive small ubiquitin-related modifier (SUMO) protease mutant, ulp1ts, suggesting that it may affect cellular SUMO dynamics. Remarkably, even a complete deletion of ULP1 is strongly suppressed. Hex3 forms a heterodimer with Slx8. We found that the Hex3.Slx8 complex has a robust substrate-specific E3 ubiquitin ligase activity. In this E3 complex, Slx8 appears to bear the core ligase function, with Hex3 strongly enhancing its activity. Notably, SUMO attachment to a substrate stimulates its Hex3.Slx8-dependent ubiquitination, primarily through direct noncovalent interactions between SUMO and Hex3. Our data reveal a novel mechanism of substrate targeting in which sumoylation of a protein can help trigger its subsequent ubiquitination by recruiting a SUMO-binding ubiquitin ligase. PMID- 17848551 TI - Thrombomodulin is a clock-controlled gene in vascular endothelial cells. AB - Cardiovascular diseases are closely related to circadian rhythm, which is under the control of an internal biological clock mechanism. Although a biological clock exists not only in the hypothalamus but also in each peripheral tissue, the biological relevance of the peripheral clock remains to be elucidated. In this study we searched for clock-controlled genes in vascular endothelial cells using microarray technology. The expression of a total of 229 genes was up-regulated by CLOCK/BMAL2. Among the genes that we identified, we examined the thrombomodulin (TM) gene further, because TM is an integral membrane glycoprotein that is expressed primarily in vascular endothelial cells and plays a major role in the regulation of intravascular coagulation. TM mRNA and protein expression showed a clear circadian oscillation in the mouse lung and heart. Reporter analyses, gel shift assays, and chromatin immunoprecipitation analyses using the TM promoter revealed that a heterodimer of CLOCK and BMAL2 binds directly to the E-box of the TM promoter, resulting in TM promoter transactivation. Indeed, the oscillation of TM gene expression was abolished in clock mutant mice, suggesting that TM expression is regulated by the clock gene in vivo. Finally, the phase of circadian oscillation of TM mRNA expression was altered by temporal feeding restriction, suggesting TM gene expression is regulated by the peripheral clock system. In conclusion, these data suggest that the peripheral clock in vascular endothelial cells regulates TM gene expression and that the oscillation of TM expression may contribute to the circadian variation of cardiovascular events. PMID- 17848552 TI - Activity-dependent regulation of h channel distribution in hippocampal CA1 pyramidal neurons. AB - The hyperpolarization-activated cation current, I(h), plays an important role in regulating intrinsic neuronal excitability in the brain. In hippocampal pyramidal neurons, I(h) is mediated by h channels comprised primarily of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel subunits, HCN1 and HCN2. Pyramidal neuron h channels within hippocampal area CA1 are remarkably enriched in distal apical dendrites, and this unique distribution pattern is critical for regulating dendritic excitability. We utilized biochemical and immunohistochemical approaches in organotypic slice cultures to explore factors that control h channel localization in dendrites. We found that distal dendritic enrichment of HCN1 is first detectable at postnatal day 13, reaching maximal enrichment by the 3rd postnatal week. Interestingly we found that an intact entorhinal cortex, which projects to distal dendrites of CA1 but not area CA3, is critical for the establishment and maintenance of distal dendritic enrichment of HCN1. Moreover blockade of excitatory neurotransmission using tetrodotoxin, 6 cyano-7-nitroquinoxaline-2,3-dione, or 2-aminophosphonovalerate redistributed HCN1 evenly throughout the dendrite without significant changes in protein expression levels. Inhibition of calcium/calmodulin-dependent protein kinase II activity, but not p38 MAPK, also redistributed HCN1 in CA1 pyramidal neurons. We conclude that activation of ionotropic glutamate receptors by excitatory temporoammonic pathway projections from the entorhinal cortex establishes and maintains the distribution pattern of HCN1 in CA1 pyramidal neuron dendrites by activating calcium/calmodulin-dependent protein kinase II-mediated downstream signals. PMID- 17848553 TI - Functional Tat transport of unstructured, small, hydrophilic proteins. AB - The twin-arginine translocation (Tat) system is a protein translocation system that is adapted to the translocation of folded proteins across biological membranes. An understanding of the folding requirements for Tat substrates is of fundamental importance for the elucidation of the transport mechanism. We now demonstrate for the first time Tat transport for fully unstructured proteins, using signal sequence fusions to naturally unfolded FG repeats from the yeast Nsp1p nuclear pore protein. The transport of unfolded proteins becomes less efficient with increasing size, consistent with only a single interaction between the system and the substrate. Strikingly, the introduction of six residues from the hydrophobic core of a globular protein completely blocked translocation. Physiological data suggest that hydrophobic surface patches abort transport at a late stage, most likely by membrane interactions during transport. This study thus explains the observed restriction of the Tat system to folded globular proteins on a molecular level. PMID- 17848554 TI - Major house dust mite allergens Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1 degrade and inactivate lung surfactant proteins A and D. AB - Lung surfactant proteins (SP) A and D are calcium-dependent carbohydrate-binding proteins. In addition to playing multiple roles in innate immune defense such as bacterial aggregation and modulation of leukocyte function, SP-A and SP-D have also been implicated in the allergic response. They interact with a wide range of inhaled allergens, competing with their binding to cell-sequestered IgE resulting in inhibition of mast cell degranulation, and exogenous administration of SP-A and SP-D diminishes allergic hypersensitivity in vivo. House dust mite allergens are a major cause of allergic asthma in the western world, and here we confirm the interaction of SP-A and SP-D with two major mite allergens, Dermatophagoides pteronyssinus 1 and Dermatophagoides farinae 1, and show that the cysteine protease activity of these allergens results in the degradation of SP-A and SP-D under physiological conditions, with multiple sites of cleavage. A recombinant fragment of SP-D that is effective in diminishing allergic hypersensitivity in mouse models of dust mite allergy was more susceptible to degradation than the native full-length protein. Degradation was enhanced in the absence of calcium, with different sites of cleavage, indicating that the calcium associated with SP A and SP-D influences accessibility to the allergens. Degradation of SP-A and SP D was associated with diminished binding to carbohydrates and to D. pteronyssinus 1 itself and diminished capacity to agglutinate bacteria. Thus, the degradation and consequent inactivation of SP-A and SP-D may be a novel mechanism to account for the potent allergenicity of these common dust mite allergens. PMID- 17848555 TI - Mitochondrial complex II in the post-ischemic heart: oxidative injury and the role of protein S-glutathionylation. AB - Mitochondrial superoxide (O2.) is an important mediator of ischemia/reperfusion (I/R) injury. The O2. generated in mitochondria also acts as a redox signal triggering cellular apoptosis. The enzyme succinate ubiquinone reductase (SQR or complex II) is one of the major mitochondrial components hosting regulatory thiols. Here the intrinsic protein S-glutathionylation (PrSSG) at the 70-kDa FAD binding subunit of SQR was detected in rat heart and in isolated SQR using an anti-GSH monoclonal antibody. When rats were subjected to 30 min of coronary ligation followed by 24 h of reperfusion, the electron transfer activity (ETA) of SQR in post-ischemic myocardium was significantly decreased by 41.5 +/- 2.9%. The PrSSGs of SQR-70 kDa were partially or completely eliminated in post-ischemic myocardium obtained from in vivo regional I/R hearts or isolated global I/R hearts, respectively. These results were further confirmed by using isolated succinate cytochrome c reductase (complex II + complex III). In the presence of succinate, O2. was generated and oxidized the SQR portion of SCR, leading to a 60 70% decrease in its ETA. The gel band of the S-glutathionylated SQR 70-kDa polypeptide was cut out and digested with trypsin, and the digests were subjected to liquid chromatography/tandem mass spectrometry analysis. One cysteine residue, Cys(90), was involved in S-glutathionylation. These results indicate that the glutathione-binding domain, (77)AAFGLSEAGFNTACVTK(93) (where underline indicates Cys(90)), is susceptible to redox change induced by oxidative stress. Furthermore, in vitro S-glutathionylation of purified SQR resulted in enhanced SQR-derived electron transfer efficiency and decreased formation of the 70-kDa derived protein thiyl radical induced by O2. . Thus, the decreasing S glutathionylation and ETA in mitochondrial complex II are marked during myocardial ischemia/reperfusion. This redox-triggered impairment of complex II occurs in the post-ischemic heart and should be useful to identify disease pathogenesis related to reactive oxygen species-induced mitochondrial dysfunction. PMID- 17848556 TI - A biochemical model of matrix metalloproteinase 9 activation and inhibition. AB - Matrix metalloproteinases (MMPs) are a class of extracellular and membrane-bound proteases involved in an array of physiological processes, including angiogenesis. We present a detailed computational model of MMP9 activation and inhibition. Our model is validated to existing biochemical experimental data. We determine kinetic rate constants for the processes of MMP9 activation by MMP3, MMP10, MMP13, and trypsin; inhibition by the tissue inhibitors of metalloproteinases (TIMPs) 1 and 2; and MMP9 deactivation. This computational approach allows us to investigate discrepancies in our understanding of the interaction of MMP9 with TIMP1. Specifically, we find that inhibition due to a single binding event cannot describe MMP9 inhibition by TIMP1. Temporally accurate biphasic inhibition requires either an additional isomerization step or a second lower affinity isoform of MMP9. We also theoretically characterize the MMP3/TIMP2/pro-MMP9 and MMP3/TIMP1/pro-MMP9 systems. We speculate that these systems differ significantly in their time scales of activation and inhibition such that MMP9 is able to temporarily overshoot its final equilibrium value in the latter. Our numerical simulations suggest that the ability of pro-MMP9 to complex TIMP1 increases this overshoot. In all, our analysis serves as a summary of existing kinetic data for MMP9 and a foundation for future models utilizing MMP9 or other MMPs under physiologically well defined microenvironments. PMID- 17848557 TI - Selective restoration of the selenoprotein population in a mouse hepatocyte selenoproteinless background with different mutant selenocysteine tRNAs lacking Um34. AB - Novel mouse models were developed in which the hepatic selenoprotein population was targeted for removal by disrupting the selenocysteine (Sec) tRNA([Ser]Sec) gene (trsp), and selenoprotein expression was then restored by introducing wild type or mutant trsp transgenes. The selenoprotein population was partially replaced in liver with mutant transgenes encoding mutations at either position 34 (34T-->A) or 37 (37A-->G) in tRNA([Ser]Sec). The A34 transgene product lacked the highly modified 5-methoxycarbonylmethyl-2'-O-methyluridine, and its mutant base A was converted to I34. The G37 transgene product lacked the highly modified N(6) isopentenyladenosine. Both mutant tRNAs lacked the 2'-methylribose at position 34 (Um34), and both supported expression of housekeeping selenoproteins (e.g. thioredoxin reductase 1) in liver but not stress-related proteins (e.g. glutathione peroxidase 1). Thus, Um34 is responsible for synthesis of a select group of selenoproteins rather than the entire selenoprotein population. The ICA anticodon in the A34 mutant tRNA decoded Cys codons, UGU and UGC, as well as the Sec codon, UGA. However, metabolic labeling of A34 transgenic mice with (75)Se revealed that selenoproteins incorporated the label from the A34 mutant tRNA, whereas other proteins did not. These results suggest that the A34 mutant tRNA did not randomly insert Sec in place of Cys, but specifically targeted selected selenoproteins. High copy numbers of A34 transgene, but not G37 transgene, were not tolerated in the absence of wild type trsp, further suggesting insertion of Sec in place of Cys in selenoproteins. PMID- 17848558 TI - The pestivirus glycoprotein Erns is anchored in plane in the membrane via an amphipathic helix. AB - E(rns) is a structural glycoprotein of pestiviruses found to be attached to the virion and to membranes within infected cells via its COOH terminus, although it lacks a hydrophobic anchor sequence. The COOH-terminal sequence was hypothesized to fold into an amphipathic alpha-helix. Alanine insertion scanning revealed that the ability of the E(rns) COOH terminus to bind membranes is considerably reduced by the insertion of a single amino acid at a wide variety of positions. Mutations decreasing the hydrophobicity of the apolar face of the putative helix led to reduction of membrane association. Proteinase K protection assays showed that E(rns) translated in vitro in the presence of microsomal membranes was protected, whereas a mutant with an artificial transmembrane region and a short cytosolic tag was shortened by the protease treatment. A tag fused to the COOH terminus of wild type E(rns) was not accessible for antibodies within digitonin-permeabilized cells, but the variant with the tag located downstream of the artificial transmembrane region was detected under the same conditions. These results are in accordance with the model that the COOH-terminal membrane anchor of E(rns) represents an amphipathic helix embedded in plane into the membrane. The integrity of the membrane anchor was found to be important for recovery of infectious virus. PMID- 17848559 TI - Unraveling tissue regeneration pathways using chemical genetics. AB - Identifying the molecular pathways that are required for regeneration remains one of the great challenges of regenerative medicine. Although genetic mutations have been useful for identifying some molecular pathways, small molecule probes of regenerative pathways might offer some advantages, including the ability to disrupt pathway function with precise temporal control. However, a vertebrate regeneration model amenable to rapid throughput small molecule screening is not currently available. We report here the development of a zebrafish early life stage fin regeneration model and its use in screening for small molecules that modulate tissue regeneration. By screening 2000 biologically active small molecules, we identified 17 that specifically inhibited regeneration. These compounds include a cluster of glucocorticoids, and we demonstrate that transient activation of the glucocorticoid receptor is sufficient to block regeneration, but only if activation occurs during wound healing/blastema formation. In addition, knockdown of the glucocorticoid receptor restores regenerative capability to nonregenerative, glucocorticoid-exposed zebrafish. To test whether the classical anti-inflammatory action of glucocorticoids is responsible for blocking regeneration, we prevented acute inflammation following amputation by antisense repression of the Pu.1 gene. Although loss of Pu.1 prevents the inflammatory response, regeneration is not affected. Collectively, these results indicate that signaling from exogenous glucocorticoids impairs blastema formation and limits regenerative capacity through an acute inflammation-independent mechanism. These studies also demonstrate the feasibility of exploiting chemical genetics to define the pathways that govern vertebrate regeneration. PMID- 17848560 TI - Mediator subunit MED28 (Magicin) is a repressor of smooth muscle cell differentiation. AB - Magicin, a protein that we isolated earlier as an interactor of the neurofibromatosis 2 protein merlin, was independently identified as MED28, a subunit of the mammalian Mediator complex. Mediator complex is an evolutionarily conserved transcriptional cofactor, which plays an essential role in positive and negative gene regulation. Distinct Mediator subunit composition is thought to contribute to gene regulation specificity based on the interaction of specific subunits with subsets of transcription factors. Here we report that down regulation of Med28 expression in NIH3T3 cells results in a significant induction of several genes associated with smooth muscle cell (SMC) differentiation. Conversely, overexpression of MED28 represses expression of SMC genes, in concordance with our knockdown data. More importantly, multipotent mesenchymal derived murine precursors can transdifferentiate into SMCs when Med28 is down regulated. Our data also show that Med28 functions as a negative regulator of SMC differentiation in concert with other Mediator subunits including Med6, Med8, and Med18 within the Mediator head module. Our results provide strong evidence that MED28 may function as a scaffolding protein by maintaining the stability of a submodule within the head module and that components of this submodule act together in a gene regulatory program to suppress SMC differentiation. The results presented here demonstrate for the first time that the mammalian Mediator subunit MED28 functions as a repressor of SMC differentiation, which could have implications for disorders associated with abnormalities in SMC growth and differentiation, including atherosclerosis, asthma, hypertension, and smooth muscle tumors. PMID- 17848562 TI - Kinetic mechanism of human dUTPase, an essential nucleotide pyrophosphatase enzyme. AB - Human dUTPase is essential in controlling relative cellular levels of dTTP/dUTP, both of which can be incorporated into DNA. The nuclear isoform of the enzyme has been proposed as a promising novel target for anticancer chemotherapeutic strategies. The recently determined three-dimensional structure of this protein in complex with an isosteric substrate analogue allowed in-depth structural characterization of the active site. However, fundamental steps of the dUTPase enzymatic cycle have not yet been revealed. This knowledge is indispensable for a functional understanding of the molecular mechanism and can also contribute to the design of potential antagonists. Here we present detailed pre-steady-state and steady-state kinetic investigations using a single tryptophan fluorophore engineered into the active site of human dUTPase. This sensor allowed distinction of the apoenzyme, enzyme-substrate, and enzyme-product complexes. We show that the dUTP hydrolysis cycle consists of at least four distinct enzymatic steps: (i) fast substrate binding, (ii) isomerization of the enzyme-substrate complex into the catalytically competent conformation, (iii) a hydrolysis (chemical) step, and (iv) rapid, nonordered release of the products. Independent quenched-flow experiments indicate that the chemical step is the rate-limiting step of the enzymatic cycle. To follow the reaction in the quenched-flow, we devised a novel method to synthesize gamma-(32)P-labeled dUTP. We also determined by indicator based rapid kinetic assays that proton release is concomitant with the rate limiting hydrolysis step. Our results led to a quantitative kinetic model of the human dUTPase catalytic cycle and to direct assessment of relative flexibilities of the C-terminal arm, critical for enzyme activity, in the enzyme-ligand complexes along the reaction pathway. PMID- 17848561 TI - WNK1 is a novel regulator of Munc18c-syntaxin 4 complex formation in soluble NSF attachment protein receptor (SNARE)-mediated vesicle exocytosis. AB - Defects in soluble NSF attachment protein receptor (SNARE)-mediated granule exocytosis occur in islet beta cells, adipocytes, and/or skeletal muscle cells correlate with increased susceptibility to insulin resistance and diabetes. The serine/threonine kinase WNK1 (with no K (lysine)) has recently been implicated in exocytosis and is expressed in all three of these cell types. To search for WNK1 substrates related to exocytosis, we conducted a WNK1 two-hybrid screen, which yielded Munc18c. Munc18c is known to be a key regulator of accessibility of the target membrane (t-SNARE) protein syntaxin 4 to participate in SNARE core complex assembly, although a paucity of Munc18c-binding factors has precluded discovery of its precise functions. To validate WNK1 as a new Munc18c-interacting partner, the direct interaction between WNK1 and Munc18c was confirmed using in vitro binding analysis, and endogenous WNK1-Munc18c complexes were detected in the cytosolic and plasma membrane compartments of the islet beta cell line MIN6. This binding interaction is mediated through the N-terminal 172 residues of Munc18c and the kinase domain residues of WNK1 (residues 159-491). Expression of either of these two minimal interaction domains resulted in inhibition of glucose stimulated insulin secretion, consistent with a functional importance for the endogenous WNK1-Munc18c complex in exocytosis. Interestingly, Munc18c failed to serve as a WNK1 substrate in kinase activity assays, suggesting that WNK1 functions in SNARE complex assembly outside its role as a kinase. Taken together, these data support a novel role for WNK1 and a new mechanism for the regulation of SNARE complex assembly by WNK1-Munc18c complexes. PMID- 17848563 TI - Suppressor mutations in the transmembrane segments of P-glycoprotein promote maturation of processing mutants and disrupt a subset of drug-binding sites. AB - Defective folding of cystic fibrosis transmembrane conductance regulator protein missing Phe508 (DeltaF508) is the major cause of cystic fibrosis. The folding defect in DeltaF508 cystic fibrosis transmembrane conductance regulator might be correctable because misfolding of a P-glycoprotein (P-gp; ABCB1) mutant lacking the equivalent residue (DeltaY490) could be corrected with drug substrates or by introduction of an arginine residue into transmembrane (TM) segments 5 (I306R) or 6 (F343R). Possible mechanisms of arginine rescue were that they mimicked some of the effects of drug substrate interactions with P-gp or that they affected global folding such that all drug substrate/modulator interactions with P-gp were altered. To distinguish between these mechanisms, we tested whether arginines introduced into other TMs predicted to line the drug-binding pocket (TM1 or TM3) would affect folding. It was found that mutation of L65R(TM1) or T199R(TM3) promoted maturation of processing mutants. We then tested whether arginine suppressor mutations had local or global effects on P-gp interactions with drug substrates and modulators. The L65R(TM1), T199R(TM3), I306R(TM5), or F343R(TM6) mutations were introduced into the P-gp mutant L339C(TM6)/F728C(TM7), and thiol cross-linking was carried out in the presence of various concentrations of vinblastine, cyclosporin A, or rhodamine B. The presence of arginine residues reduced the apparent affinity of P-gp for vinblastine (L65R, T199R, and I306R), cyclosporin (I306R and F343R), or rhodamine B (F343R) by 4-60-fold. These results show that the arginine mutations affect a subset of drug-binding sites and suggest that they rescue processing mutants by mimicking drug substrate interactions with P-gp. PMID- 17848564 TI - A muscle-specific promoter directs Pitx3 gene expression in skeletal muscle cells. AB - The Pitx homeobox transcription factor genes have been implicated in different developmental processes, including determination of hind limb identity for Pitx1, left-right asymmetry for Pitx2, and eye development and survival of midbrain dopaminergic neurons for Pitx3. Pitx1 and Pitx2 have partly redundant activities in craniofacial development, including in pituitary organogenesis, as indicated by their names. These genes also exhibit redundant activities in the control of hind limb bud growth. Recent studies have shown expression of the three Pitx genes in muscle, with Pitx3 being the most widely expressed in all skeletal muscles. We now report the identification of a muscle-specific promoter within the Pitx3 gene that is situated between the first exon for eye and brain expression and exon 2 that contains the initiator ATG codon. Sequences proximal to this muscle-specific exon 1 are essential and sufficient to confer muscle specific expression in transgenic mice, they are responsive to myogenic basic helix-loop-helix regulatory factors, and they recruit these factors in vivo. In agreement with exclusive use of the muscle-specific promoter in aphakia mice that are deleted of the brain promoter, the trimethyl-lysine 4 histone H3 promoter signature shifts to this promoter in embryonic day 13 ak limb bud muscle cells. Myogenic basic helix-loop-helix regulatory factor activation of Pitx3 transcription may be part of a positive feedback loop contributing to establishment of the myogenic program. PMID- 17848565 TI - Regulation of arrestin binding by rhodopsin phosphorylation level. AB - Arrestins ensure the timely termination of receptor signaling. The role of rhodopsin phosphorylation in visual arrestin binding was established more than 20 years ago, but the effects of the number of receptor-attached phosphates on this interaction remain controversial. Here we use purified rhodopsin fractions with carefully quantified content of individual phosphorylated rhodopsin species to elucidate the impact of phosphorylation level on arrestin interaction with three biologically relevant functional forms of rhodopsin: light-activated and dark phosphorhodopsin and phospho-opsin. We found that a single receptor-attached phosphate does not facilitate arrestin binding, two are necessary to induce high affinity interaction, and three phosphates fully activate arrestin. Higher phosphorylation levels do not increase the stability of arrestin complex with light-activated rhodopsin but enhance its binding to the dark phosphorhodopsin and phospho-opsin. The complex of arrestin with hyperphosphorylated light activated rhodopsin is less sensitive to high salt and appears to release retinal faster. These data suggest that arrestin likely quenches rhodopsin signaling after the third phosphate is added by rhodopsin kinase. The complex of arrestin with heavily phosphorylated rhodopsin, which appears to form in certain disease states, has distinct characteristics that may contribute to the phenotype of these visual disorders. PMID- 17848566 TI - Critical role of desolvation in the binding of 20-hydroxyecdysone to the ecdysone receptor. AB - The insect steroid hormone 20-hydroxyecdysone (20E) binds to its cognate nuclear receptor composed of the ecdysone receptor (EcR) and Ultraspiracle (USP) and triggers the main developmental transitions, in particular molting and metamorphosis. We present the crystal structure of the ligand-binding domains of EcR/USP in complex with 20E at 2.4A resolution and compare it with published structures of EcR/USP bound to ponasterone A (ponA). ponA is essentially identical to 20E but lacks the 25-OH group of 20E. The structure of 20E-bound EcR indicates that an additional hydrogen bond is formed compared with the ponA-bound receptor, yet, paradoxically, ponA has a significantly higher affinity for EcR than 20E. Theoretical studies based on docking and free energy methods lead to a rationale for understanding the difference in binding affinities between 20E and ponA. Results of the calculations indicate that the favorable contribution from the extra H-bond made by 25-OH of 20E is counterbalanced by its larger desolvation cost compared with that of ponA. The contribution of 25-OH to the binding affinity is further compared with those of 20- and 22-OH groups. Ligands that lack the 20- or 22-OH group are indeed known to bind less favorably to EcR than 20E, an effect opposite to that observed for ponA. The results indicate that their respective contributions to receptor-ligand complex stability reside mostly in their different contributions to solvation/desolvation. Together, the data demonstrate the critical role of ligand desolvation in determining binding affinity, with general implications for the binding of hormones to their cognate nuclear receptors. PMID- 17848567 TI - Derepression of microRNA-mediated protein translation inhibition by apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) and its family members. AB - The apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or A3G) and its fellow cytidine deaminase family members are potent restrictive factors for human immunodeficiency virus type 1 (HIV-1) and many other retroviruses. A3G interacts with a vast spectrum of RNA-binding proteins and is located in processing bodies and stress granules. However, its cellular function remains to be further clarified. Using a luciferase reporter gene and green fluorescent protein reporter gene, we demonstrate that A3G and other APOBEC family members can counteract the inhibition of protein synthesis by various microRNAs (miRNAs) such as mir-10b, mir-16, mir-25, and let-7a. A3G could also enhance the expression level of miRNA-targeted mRNA. Further, A3G facilitated the association of microRNA-targeted mRNA with polysomes rather than with processing bodies. Intriguingly, experiments with a C288A/C291A A3G mutant indicated that this function of A3G is separable from its cytidine deaminase activity. Our findings suggest that the major cellular function of A3G, in addition to inhibiting the mobility of retrotransposons and replication of endogenous retroviruses, is most likely to prevent the decay of miRNA-targeted mRNA in processing bodies. PMID- 17848568 TI - Alternative splicing yields protein arginine methyltransferase 1 isoforms with distinct activity, substrate specificity, and subcellular localization. AB - PRMT1 is the predominant member of a family of protein arginine methyltransferases (PRMTs) that have been implicated in various cellular processes, including transcription, RNA processing, and signal transduction. It was previously reported that the human PRMT1 pre-mRNA was alternatively spliced to yield three isoforms with distinct N-terminal sequences. Close inspection of the genomic organization in the 5'-end of the PRMT1 gene revealed that it can produce up to seven protein isoforms, all varying in their N-terminal domain. A detailed biochemical characterization of these variants revealed that unique N terminal sequences can influence catalytic activity as well as substrate specificity. In addition, our results uncovered the presence of a functional nuclear export sequence in PRMT1v2. Finally, we find that the relative balance of PRMT1 isoforms is altered in breast cancer. PMID- 17848569 TI - The interaction of Akt with APPL1 is required for insulin-stimulated Glut4 translocation. AB - APPL1 (adaptor protein containing PH domain, PTB domain, and leucine zipper motif 1) is an Akt/protein kinase B-binding protein involved in signal transduction and membrane trafficking pathways for various receptors, including receptor tyrosine kinases. Here, we establish a role for APPL1 in insulin signaling in which we demonstrate its interaction with Akt2 by co-immunoprecipitation and pulldown assays. In primary rat adipocytes and skeletal muscle, APPL1 and Akt2 formed a complex that was dissociated upon insulin stimulation in both tissues. To investigate possible APPL1 function in adipocytes, we analyzed Akt phosphorylation, 2-deoxyglucose uptake, and Glut4 translocation by immunofluorescence following APPL1 knockdown by small interfering and short hairpin RNAs. We show that APPL1 knockdown suppressed Akt phosphorylation, glucose uptake, and Glut4 translocation. We also tested the effect in 3T3-L1 adipocytes of expressing full-length APPL1 or an N- or a C-terminal APPL1 construct. Interestingly, expression of full-length APPL1 and its N terminus suppressed insulin-stimulated 2-deoxyglucose uptake and Glut4 translocation to roughly the same extent (40-60%). We confirmed by cellular fractionation that Glut4 translocation was substantially blocked in 3T3-L1 adipocytes transfected with full-length APPL1. By cellular fractionation, APPL1 was localized mainly in the cytosol, and it showed a small degree of re-localization to the light microsomes and nucleus in response to insulin. By immunofluorescence, we also show that APPL1 partially co-localized with Glut4. These data suggest that APPL1 plays an important role in insulin-stimulated Glut4 translocation in muscle and adipose tissues and that its N-terminal portion may be critical for APPL1 function. PMID- 17848570 TI - Role of MAPK phosphatase-1 in sustained activation of JNK during ethanol-induced apoptosis in hepatocyte-like VL-17A cells. AB - Ethanol metabolism plays a central role in activating the mitogen-activated protein kinase (MAPK) cascade leading to inflammation and apoptosis. Sustained activation of c-Jun N-terminal kinase (JNK), one of the MAPKs, has been shown to induce apoptosis in hepatocytes. MAPK phosphatase-1 (MKP-1) has been shown to dephosphorylate MAPKs in several cells. The aim of the study is to evaluate the role of MKP-1 in sustained JNK activation as a mechanism to explain ethanol induced hepatocyte apoptosis. VL-17A cells (HepG2 cells overexpressing alcohol dehydrogenase and cytochrome P450-2E1) were exposed to ethanol for different time periods. Western blots were performed for MKP-1, phospho-JNK, phosphotyrosine, and protein kinase Cdelta (PKCdelta). Electrophoretic mobility shift assays for AP-1 were performed. Apoptosis was measured by caspase-3 activity assay, TUNEL, and 4',6-diamidino-2-phenylindole staining. Reactive oxygen species were neutralized by overexpressing both superoxide dismutase-3 and catalase genes using lentiviral vectors in VL-17A cells. Ethanol incubation markedly decreased the MKP-1 protein levels to 15% of control levels and was associated with sustained phosphorylation of p46 JNK and p54 JNK, as well as increased apoptosis. VL-17A cells overexpressing superoxide dismutase-3 and catalase, treatment with a tyrosine kinase inhibitor, or incubation of the cells with PKCdelta small interference RNAs significantly inhibited the ethanol-induced MKP-1 degradation and apoptosis. Ethanol-induced oxidative stress enhanced the tyrosine phosphorylation of PKCdelta, which in turn caused the proteasomal degradation of MKP-1, leading to sustained JNK activation and increased apoptosis in VL-17A cells. PMID- 17848571 TI - Elucidation of a complete kinetic mechanism for a mammalian hydroxysteroid dehydrogenase (HSD) and identification of all enzyme forms on the reaction coordinate: the example of rat liver 3alpha-HSD (AKR1C9). AB - Hydroxysteroid dehydrogenases (HSDs) are essential for the biosynthesis and mechanism of action of all steroid hormones. We report the complete kinetic mechanism of a mammalian HSD using rat 3alpha-HSD of the aldo-keto reductase superfamily (AKR1C9) with the substrate pairs androstane-3,17-dione and NADPH (reduction) and androsterone and NADP(+) (oxidation). Steady-state, transient state kinetics, and kinetic isotope effects reconciled the ordered bi-bi mechanism, which contained 9 enzyme forms and permitted the estimation of 16 kinetic constants. In both reactions, loose association of the NADP(H) was followed by two conformational changes, which increased cofactor affinity by >86 fold. For androstane-3,17-dione reduction, the release of NADP(+) controlled k(cat), whereas the chemical event also contributed to this term. k(cat) was insensitive to [(2)H]NADPH, whereas (D)k(cat)/K(m) and the (D)k(lim) (ratio of the maximum rates of single turnover) were 1.06 and 2.06, respectively. Under multiple turnover conditions partial burst kinetics were observed. For androsterone oxidation, the rate of NADPH release dominated k(cat), whereas the rates of the chemical event and the release of androstane-3,17-dione were 50-fold greater. Under multiple turnover conditions full burst kinetics were observed. Although the internal equilibrium constant favored oxidation, the overall K(eq) favored reduction. The kinetic Haldane and free energy diagram confirmed that K(eq) was governed by ligand binding terms that favored the reduction reactants. Thus, HSDs in the aldo-keto reductase superfamily thermodynamically favor ketosteroid reduction. PMID- 17848572 TI - UDP-glucuronosyltransferase 2B15 (UGT2B15) and UGT2B17 enzymes are major determinants of the androgen response in prostate cancer LNCaP cells. AB - Uridine diphosphate-glucuronosyltransferase 2 (UGT2)B15 and B17 enzymes conjugate dihydrotestosterone (DHT) and its metabolites androstane-3alpha, 17beta-diol (3alpha-DIOL) and androsterone (ADT). The presence of UGT2B15/B17 in the epithelial cells of the human prostate has been clearly demonstrated, and significant 3alpha-DIOL glucuronide and ADT-glucuronide concentrations have been detected in this tissue. The human androgen-dependent cancer cell line, LNCaP, expresses UGT2B15 and -B17 and is also capable of conjugating androgens. To assess the impact of these two genes in the inactivation of androgens in LNCaP cells, their expression was inhibited using RNA interference. The efficient inhibitory effects of a UGT2B15/B17 small interfering RNA (siRNA) probe was established by the 70% reduction of these UGT mRNA levels, which was further confirmed at the protein levels. The glucuronidation of dihydrotestosterone (DHT), 3alpha-DIOL, and ADT by LNCaP cell homogenates was reduced by more than 75% in UGT2B15/B17 siRNA-transfected LNCaP cells when compared with cells transfected with a non-target probe. In UGT2B15/B17-deficient LNCaP cells, we observe a stronger response to DHT than in control cells, as determined by cell proliferation and expression of eight known androgen-sensitive genes. As expected, the amounts of DHT in cell culture media from control cells were significantly lower than that from UGT2B15/B17 siRNA-treated cells, which was caused by a higher conversion to its corresponding glucuronide derivative. Taken together these data support the idea that UGT2B15 and -B17 are critical enzymes for the local inactivation of androgens and that glucuronidation is a major determinant of androgen action in prostate cells. PMID- 17848573 TI - Plasminogen structural domains exhibit different functions when associated with cell surface GRP78 or the voltage-dependent anion channel. AB - Both the voltage-dependent anion channel and the glucose-regulated protein 78 have been identified as plasminogen kringle 5 receptors on endothelial cells. In this study, we demonstrate that kringle 5 binds to a region localized in the N terminal domain of the glucose-regulated protein 78, whereas microplasminogen does so through the C-terminal domain of the glucose-regulated protein 78. Both plasminogen fragments induce Ca(2+) signaling cascades; however, kringle 5 acts through voltage-dependent anion channel and microplasminogen does so via the glucose-regulated protein 78. Because trafficking of voltage-dependent anion channel to the cell surface is associated with heat shock proteins, we investigated a possible association between voltage-dependent anion channel and glucose-regulated protein 78 on the surface of 1-LN human prostate tumor cells. We demonstrate that these proteins co-localize, and changes in the expression of the glucoseregulated protein 78 affect the expression of voltage-dependent anion channel. To differentiate the functions of these receptor proteins, either when acting singly or as a complex, we employed human hexokinase I as a specific ligand for voltage-dependent anion channel, in addition to kringle 5. We show that kringle 5 inhibits 1-LN cell proliferation and promotes caspase-7 activity by a mechanism that requires binding to cell surface voltage-dependent anion channel and is inhibited by human hexokinase I. PMID- 17848574 TI - MDM2 chaperones the p53 tumor suppressor. AB - The murine double minute (mdm2) gene encodes an E3 ubiquitin ligase that plays a key role in the degradation of p53 tumor suppressor protein. Nevertheless recent data highlight other p53-independent functions of MDM2. Given that MDM2 protein binds ATP, can interact with the Hsp90 chaperone, plays a role in the modulation of transcription factors and protection and activation of DNA polymerases, and is involved in ribosome assembly and nascent p53 protein biosynthesis, we have evaluated and found MDM2 protein to possess an intrinsic molecular chaperone activity. MDM2 can substitute for the Hsp90 molecular chaperone in promoting binding of p53 to the p21-derived promoter sequence. This reaction is driven by recycling of MDM2 from the p53 complex, triggered by binding of ATP to MDM2. The ATP binding mutant MDM2 protein (K454A) lacks the chaperone activity both in vivo and in vitro. Mdm2 cotransfected in the H1299 cell line with wild-type p53 stimulates efficient p53 folding in vivo but at the same time accelerates the degradation of p53. MDM2 in which one of the Zn(2+) coordinating residues is mutated (C478S or C464A) blocks degradation but enhances folding of p53. This is the first demonstration that MDM2 possesses an intrinsic molecular chaperone activity, indicating that the ATP binding function of MDM2 can mediate its chaperone function toward the p53 tumor suppressor. PMID- 17848575 TI - Unique hydrophobic extension of the RGS2 amphipathic helix domain imparts increased plasma membrane binding and function relative to other RGS R4/B subfamily members. AB - RGS2 and RGS5 are inhibitors of G-protein signaling belonging to the R4/B subfamily of RGS proteins. We here show that RGS2 is a much more potent attenuator of M1 muscarinic receptor signaling than RGS5. We hypothesize that this difference is mediated by variation in their ability to constitutively associate with the plasma membrane (PM). Compared with full-length RGS2, the RGS box domains of RGS2 and RGS5 both show reduced PM association and activity. Prenylation of both RGS-box domains increases activity to RGS2 levels, demonstrating that lipid bilayer targeting increases RGS domain function. Amino terminal domain swaps confirm that key determinants of localization and function are found within this important regulatory domain. An RGS2 amphipathic helix domain mutant deficient for phospholipid binding (L45D) shows reduced PM association and activity despite normal binding to the M1 muscarinic receptor third intracellular loop and activated Galpha(q). Replacement of a unique dileucine motif adjacent to the RGS2 helix with corresponding RGS5 residues disrupts both PM localization and function. These data suggest that RGS2 contains a hydrophobic extension of its helical domain that imparts high efficiency binding to the inner leaflet of the lipid bilayer. In support of this model, disruption of membrane phospholipid composition with N-ethylmaleimide reduces PM association of RGS2, without affecting localization of the M1 receptor or Galpha(q). Together, these data indicate that novel features within the RGS2 amphipathic alpha helix facilitate constitutive PM targeting and more efficient inhibition of M1 muscarinic receptor signaling than RGS5 and other members of the R4/B subfamily. PMID- 17848576 TI - Juxtacrine activation of epidermal growth factor (EGF) receptor by membrane anchored heparin-binding EGF-like growth factor protects epithelial cells from anoikis while maintaining an epithelial phenotype. AB - Loss of cell-matrix adhesion is often associated with acute epithelial injury, suggesting that "anoikis" may be an important contributor to cell death. Resistance against anoikis is a key characteristic of transformed cells. When nontransformed epithelia are injured, activation of the epidermal growth factor (EGF) receptor (EGFR) by paracrine/autocrine release of soluble ligands can induce a prosurvival program, but there is generally evidence for concomitant dedifferentiation. The EGFR ligand, heparin-binding EGF-like growth factor (HB EGF), is synthesized as a membrane-anchored precursor that can activate the EGFR via juxtacrine signaling or can be released and act as a soluble growth factor. In Madin-Darby canine kidney cells, expression of membrane-anchored HB-EGF increases cell-cell and cell-matrix adhesion. Therefore, these studies were designed to test the effects of juxtacrine HB-EGF signaling upon cell survival and epithelial integrity when cells are denied proper cell-matrix interactions. Cells expressing a noncleavable mutated form of membrane-anchored HB-EGF demonstrated increased survival from anoikis, formed larger cell aggregates, and maintained epithelial characteristics even following prolonged detachment from the substratum. Physical association between membrane-anchored HB-EGF and EGFR was observed. Signaling studies indicated synergistic effects of EGFR activation and phosphatidylinositol 3-kinase signaling to regulate apoptotic and survival pathways. In contrast, although administration of exogenous EGF partially suppressed anoikis in wild type cells, it also led to an increased expression of mesenchymal markers, suggesting dedifferentiation. Taken together, we propose a novel role for membrane-anchored HB-EGF in the cytoprotection of epithelial cells. PMID- 17848577 TI - Accumulation of glucosylceramide in murine testis, caused by inhibition of beta glucosidase 2: implications for spermatogenesis. AB - One of the hallmarks of male germ cell development is the formation of a specialized secretory organelle, the acrosome. This process can be pharmacologically disturbed in C57BL/6 mice, and thus infertility can be induced, by small molecular sugar-like compounds (alkylated imino sugars). Here the biochemical basis of this effect has been investigated. Our findings suggest that in vivo alkylated imino sugars primarily interact with the non-lysosomal glucosylceramidase. This enzyme cleaves glucosylceramide into glucose and ceramide, is sensitive to imino sugars in vitro, and has been characterized as beta-glucosidase 2 (GBA2). Imino sugars raised the level of glucosylceramide in brain, spleen, and testis, in a dose-dependent fashion. In testis, multiple species of glucosylceramide were similarly elevated, those having long acyl chains (C16-24), as well as those with very long polyunsaturated acyl chains (C28 30:5). Both of these GlcCer species were also increased in the testes from GBA2 deficient mice. When considering that the very long polyunsaturated sphingolipids are restricted to germ cells, these results indicate that in the testis GBA2 is present in both somatic and germ cells. Furthermore, in all mouse strains tested imino sugar treatment caused a rise in testicular glucosylceramide, even in a number of strains, of which the males remain fertile after drug administration. Therefore, it appears that acrosome formation can be derailed by accumulation of glucosylceramide in an extralysosomal localization, and that the sensitivity of male germ cells to glucosylceramide is genetically determined. PMID- 17848578 TI - Structural requirements for the BARD1 tumor suppressor in chromosomal stability and homology-directed DNA repair. AB - The BRCA1 tumor suppressor exists as a heterodimeric complex with BARD1, and this complex is thought to mediate many of the functions ascribed to BRCA1, including its role in tumor suppression. The two proteins share a common structural organization that features an N-terminal RING domain and two C-terminal BRCT motifs, whereas BARD1 alone also contains three tandem ankyrin repeats. In normal cells, the BRCA1/BARD1 heterodimer is believed to enhance chromosome stability by promoting homology-directed repair (HDR) of double strand DNA breaks. Here we have investigated the structural requirements for BARD1 in this process by complementation of Bard1-null mouse mammary carcinoma cells. Our results demonstrate that the ankyrin and BRCT motifs of BARD1 are each essential for both chromosome stability and HDR. Tandem BRCT motifs, including those found at the C terminus of BARD1, are known to form a phosphoprotein recognition module. Nonetheless, the HDR function of BARD1 was not perturbed by synthetic mutations predicted to ablate the phospho-recognition activity of its BRCT sequences, suggesting that some functions of the BRCT domains are not dependent on their ability to bind phosphorylated ligands. Also, cancer-associated missense mutations in the BRCT domains of BARD1 (e.g. C557S, Q564H, V695L, and S761N) have been observed in patients with breast, ovarian, and endometrial tumors. However, none of these was found to affect the HDR activity of BARD1, suggesting that any increased cancer risk conferred by these mutations is not because of defects in this repair mechanism. PMID- 17848579 TI - Dynamin is functionally coupled to insulin granule exocytosis. AB - The insulin granule integral membrane protein marker phogrin-green fluorescent protein was co-localized with insulin in Min6B1 beta-cell secretory granules but did not undergo plasma membrane translocation following glucose stimulation. Surprisingly, although expression of a dominant-interfering dynamin mutant (Dyn/K44A) inhibited transferrin receptor endocytosis, it had no effect on phogringreen fluorescent protein localization in the basal or secretagogue stimulated state. By contrast, co-expression of Dyn/K44A with human growth hormone as an insulin secretory marker resulted in a marked inhibition of human growth hormone release by glucose, KCl, and a combination of multiple secretagogues. Moreover, serial pulse depolarization stimulated an increase in cell surface capacitance that was also blocked in cells expressing Dyn/K44A. Similarly, small interference RNA-mediated knockdown of dynamin resulted in marked inhibition of glucose-stimulated insulin secretion. Together, these data suggest the presence of a selective kiss and run mechanism of insulin release. Moreover, these data indicate a coupling between endocytosis and exocytosis in the regulation of beta-cell insulin secretion. PMID- 17848580 TI - NKCC2 surface expression in mammalian cells: down-regulation by novel interaction with aldolase B. AB - Apical bumetanide-sensitive Na(+)-K(+)-2Cl(-) co-transporter, termed NKCC2, is the major salt transport pathway in kidney thick ascending limb. NKCC2 surface expression is subject to regulation by intracellular protein trafficking. However, the protein partners involved in the intracellular trafficking of NKCC2 remain unknown. Moreover, studies aimed at under-standing the post-translational regulation of NKCC2 have been hampered by the difficulty to express NKCC2 protein in mammalian cells. Here we were able to express NKCC2 protein in renal epithelial cells by tagging its N-terminal domain. To gain insights into the regulation of NKCC2 trafficking, we screened for interaction partners of NKCC2 with the yeast two-hybrid system, using the C-terminal tail of NKCC2 as bait. Aldolase B was identified as a dominant and novel interacting protein. Real time PCR on renal microdissected tubules demonstrated the expression of aldolase B in the thick ascending limb. Co-immunoprecipitation and co-immunolocalization experiments confirmed NKCC2-aldolase interaction in renal cells. Biotinylation assays showed that aldolase co-expression reduces NKCC2 surface expression. In the presence of aldolase substrate, fructose 1,6-bisphosphate, aldolase binding was disrupted, and aldolase co-expression had no further effect on the cell surface level of NKCC2. Finally, functional studies demonstrated that aldolase induced down-regulation of NKCC2 at the plasma membrane was associated with a decrease in its transport activity. In summary, we identified aldolase B as a novel NKCC2 binding partner that plays a key role in the modulation of NKCC2 surface expression, thereby revealing a new regulatory mechanism governing the co transporter intracellular trafficking. Furthermore, NKCC2 protein expression in mammalian cells and its regulation by protein-protein interactions, described here, may open new and important avenues in studying the cell biology and post transcriptional regulation of the co-transporter. PMID- 17848581 TI - Pharmacologic inhibition of tpl2 blocks inflammatory responses in primary human monocytes, synoviocytes, and blood. AB - Tumor necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine that controls the initiation and progression of inflammatory diseases such as rheumatoid arthritis. Tpl2 is a MAPKKK in the MAPK (i.e. ERK) pathway, and the Tpl2-MEK-ERK signaling pathway is activated by the pro-inflammatory mediators TNFalpha, interleukin (IL)-1beta, and bacterial endotoxin (lipopolysaccharide (LPS)). Moreover, Tpl2 is required for TNFalpha expression. Thus, pharmacologic inhibition of Tpl2 should be a valid approach to therapeutic intervention in the pathogenesis of rheumatoid arthritis and other inflammatory diseases in humans. We have developed a series of highly selective and potent Tpl2 inhibitors, and in the present study we have used these inhibitors to demonstrate that the catalytic activity of Tpl2 is required for the LPS-induced activation of MEK and ERK in primary human monocytes. These inhibitors selectively target Tpl2 in these cells, and they block LPS- and IL-1beta-induced TNFalpha production in both primary human monocytes and human blood. In rheumatoid arthritis fibroblast-like synoviocytes these inhibitors block ERK activation, cyclooxygenase-2 expression, and the production of IL-6, IL-8, and prostaglandin E(2), and the matrix metalloproteinases MMP-1 and MMP-3. Taken together, our results show that inhibition of Tpl2 in primary human cell types can decrease the production of TNFalpha and other pro-inflammatory mediators during inflammatory events, and they further support the notion that Tpl2 is an appropriate therapeutic target for rheumatoid arthritis and other human inflammatory diseases. PMID- 17848582 TI - Effect of line tension on the lateral organization of lipid membranes. AB - The principles of organization and functioning of cellular membranes are currently not well understood. The raft hypothesis suggests the existence of domains or rafts in cell membranes, which behave as protein and lipid platforms. They have a functional role in important cellular processes, like protein sorting or cell signaling, among others. Theoretical work suggests that the interfacial energy at the domain edge, also known as line tension, is a key parameter determining the distribution of domain sizes, but there is little evidence of how line tension affects membrane organization. We have investigated the effects of the line tension on the formation and stability of liquid ordered domains in model lipid bilayers with raft-like composition by means of time-lapse confocal microscopy coupled to atomic force microscopy. We varied the hydrophobic mismatch between the two phases, and consequently the line tension, by modifying the thickness of the disordered phase with phosphatidylcholines of different acyl chain length. The temperature of domain formation, the dynamics of domain growth, and the distribution of domain sizes depend strongly on the thickness difference between the domains and the surrounding membrane, which is related to line tension. When considering line tension calculated from a theoretical model, our results revealed a linear increase of the temperature of domain formation and domain growth rate with line tension. Domain budding was also shown to depend on height mismatch. Our experiments contribute significantly to our knowledge of the physical-chemical parameters that control membrane organization. Importantly, the general trends observed can be extended to cellular membranes. PMID- 17848583 TI - ABCG1 is deficient in alveolar macrophages of GM-CSF knockout mice and patients with pulmonary alveolar proteinosis. AB - Patients with pulmonary alveolar proteinosis (PAP) display impaired surfactant clearance, foamy, lipid-filled alveolar macrophages, and increased cholesterol metabolites within the lung. Neutralizing autoantibodies to granulocyte macrophage colony-stimulating factor (GM-CSF) are also present, resulting in virtual GM-CSF deficiency. We investigated ABCG1 and ABCA1 expression in alveolar macrophages of PAP patients and GM-CSF knockout (KO) mice, which exhibit PAP-like pulmonary pathology and increased pulmonary cholesterol. Alveolar macrophages from both sources displayed a striking similarity in transporter gene dysregulation, consisting of deficient ABCG1 accompanied by highly increased ABCA1. Peroxisome proliferator-activated receptor gamma (PPARgamma), a known regulator of both transporters, was deficient, as reported previously. In contrast, the liver X receptor alpha, which also upregulates both transporters, was highly increased. GM-CSF treatment increased ABCG1 expression in macrophages in vitro and in PAP patients in vivo. Overexpression of PPARgamma by lentivirus PPARgamma transduction of primary alveolar macrophages, or activation by rosiglitazone, also increased ABCG1 expression. These results suggest that ABCG1 deficiency in PAP and GM-CSF KO alveolar macrophages is attributable to the absence of a GM-CSF-mediated PPARgamma pathway. These findings document the existence of ABCG1 deficiency in human lung disease and highlight a critical role for ABCG1 in surfactant homeostasis. PMID- 17848584 TI - Ion-trap tandem mass spectrometric analysis of squalene monohydroperoxide isomers in sunlight-exposed human skin. AB - We previously discovered that squalene monohydroperoxide (SQ-OOH) was produced on human forehead skin and suggested that skin squalene (SQ) may be the principal target lipid for oxidative stress (e.g., sunlight exposure). Because of its six double bonds, SQ peroxidation can yield various positional hydroperoxide isomers. However, the structural characterization of skin SQ-OOH isomers has never been reported. Here, we prepared pure SQ-OOH isomers and developed an analytical method for SQ-OOH isomers using a quadrupole/linear ion-trap mass spectrometer (QTRAP) MS/MS system. Collision-induced dissociation produced specific fragment ions for each SQ-OOH isomer, which permitted discrimination between SQ-OOH isomers by multiple reaction monitoring (MRM). When lipid extract from human forehead skin was subjected to LC-MS/MS with MRM, individual SQ-OOH isomers could be separated and detected with a sensitivity of 0.05 ng/injection. The total concentration of SQ-OOH isomers in forehead skin was approximately 956 microg/g skin lipids, but it increased up to 2,760 microg/g skin lipids after 3 h of sunlight exposure. The LC-MS/MS method was useful for investigating the peroxidation mechanisms of SQ as well as SQ-OOH-mediated skin disorders. PMID- 17848585 TI - Proteomics analysis of serum from mutant mice reveals lysosomal proteins selectively transported by each of the two mannose 6-phosphate receptors. AB - Most mammalian cells contain two types of mannose 6-phosphate (Man-6-P) receptors (MPRs): the 300 kDa cation-independent (CI) MPR and 46 kDa cation-dependent (CD) MPR. The two MPRs have overlapping function in intracellular targeting of newly synthesized lysosomal proteins, but both are required for efficient targeting. Despite extensive investigation, the relative roles and specialized functions of each MPR in targeting of specific proteins remain questions of fundamental interest. One possibility is that most Man-6-P glycoproteins are transported by both MPRs, but there may be subsets that are preferentially transported by each. To investigate this, we have conducted a proteomics analysis of serum from mice lacking either MPR with the reasoning that lysosomal proteins that are selectively transported by a given MPR should be preferentially secreted into the bloodstream in its absence. We purified and identified Man-6-P glycoproteins and glycopeptides from wild-type, CDMPR-deficient, and CIMPR-deficient mouse serum and found both lysosomal proteins and proteins not currently thought to have lysosomal function. Different mass spectrometric approaches (spectral count analysis of nanospray LC-MS/MS experiments on unlabeled samples and LC MALDI/TOF/TOF experiments on iTRAQ-labeled samples) revealed a number of proteins that appear specifically elevated in serum from each MPR-deficient mouse. Man-6-P glycoforms of cellular repressor of E1A-stimulated genes 1, tripeptidyl peptidase I, and heparanase were elevated in absence of the CDMPR and Man-6-P glycoforms of alpha-mannosidase B1, cathepsin D, and prosaposin were elevated in the absence of the CIMPR. Results were confirmed by Western blot analyses for select proteins. This study provides a comparison of different quantitative mass spectrometric approaches and provides the first report of proteins whose cellular targeting appears to be MPR-selective under physiological conditions. PMID- 17848586 TI - A combined proteome and transcriptome analysis of developing Medicago truncatula seeds: evidence for metabolic specialization of maternal and filial tissues. AB - A comparative study of proteome and transcriptome changes during Medicago truncatula (cultivar Jemalong) seed development has been carried out. Transcript and protein profiles were parallel across the time course for 50% of the comparisons made, but divergent patterns were also observed, indicative of post transcriptional events. These data, combined with the analysis of transcript and protein distribution in the isolated seed coat, endosperm, and embryo, demonstrated the major contribution made to the embryo by the surrounding tissues. First, a remarkable compartmentalization of enzymes involved in methionine biosynthesis between the seed tissues was revealed that may regulate the availability of sulfur-containing amino acids for embryo protein synthesis during seed filling. This intertissue compartmentalization, which was also apparent for enzymes of sulfur assimilation, is relevant to strategies for modifying the nutritional value of legume seeds. Second, decreasing levels during seed filling of seed coat and endosperm metabolic enzymes, including essential steps in Met metabolism, are indicative of a metabolic shift from a highly active to a quiescent state as the embryo assimilates nutrients. Third, a concomitant persistence of several proteases in seed coat and endosperm highlighted the importance of proteolysis in these tissues as a supplementary source of amino acids for protein synthesis in the embryo. Finally, the data revealed the sites of expression within the seed of a large number of transporters implied in nutrient import and intraseed translocations. Several of these, including a sulfate transporter, were preferentially expressed in seeds compared with other plant organs. These findings provide new directions for genetic improvement of grain legumes. PMID- 17848587 TI - Isotope-labeled protein standards: toward absolute quantitative proteomics. AB - Diagnostic development and public health surveillance require technologies that provide specific identification and absolute quantification of protein biomarkers. Beside immunologically related techniques (e.g. enzyme-linked immunosorbent assay), MS is gaining increasing interest due to its high sensitivity and specificity. Furthermore, MS-based analyses are extremely accurate quantitatively, provided that suitable reference standards are available. Recently, the use of chemically synthesized isotope-labeled marker peptides for MS-based absolute quantification of proteins has led to major advances. However, we show here that the use of such peptides can lead to severe biases. In this work, we present an innovative strategy (Protein Standard Absolute Quantification) that uses in vitro-synthesized isotope-labeled full length proteins as standards for absolute quantification. As those protein standards perfectly match the biochemical properties of the target proteins, they can be directly added into the samples to be analyzed, allowing a highly accurate quantification of proteins even in prefractionated complex samples. The power of our Protein Standard Absolute Quantification methodology for accurate absolute quantification of biomarkers was demonstrated both on water and urine samples contaminated with Staphylococcus aureus superantigenic toxins as typical biomarkers of public health interest. PMID- 17848589 TI - A proteomics analysis of cell signaling alterations in colorectal cancer. AB - To gain further insight into alterations in cellular pathways, tumor profiling, and marker discovery in colorectal cancer (CRC) we used a new antibody microarray specific for cell signaling. Soluble protein extracts were prepared from paired tumor/normal biopsies of 11 patients diagnosed with colorectal carcinoma at different stages; four liver carcinomas were used as a reference. Antibody microarray analysis identified 46 proteins that were differentially expressed between normal colorectal epithelium and adenocarcinoma. These proteins gave a specific signature for CRC, different from other tumors, as well as a panel of novel markers and potential targets for CRC. Twenty-four proteins were validated by using a specific colorectal cancer tissue microarray and immunoblotting analysis. Together with some previously well known deregulated proteins in CRC (beta-catenin, c-MYC, or p63), we found new potential markers preferentially expressed in CRC tumors: cytokeratin 13, calcineurin, CHK1, clathrin light chain, MAPK3, phospho-PTK2/focal adhesion kinase (Ser-910), and MDM2. CHK1 antibodies were particularly effective in discriminating between tumoral and normal mucosa in CRC. Moreover a global picture of alterations in signaling pathways in CRC was observed, including a significant up-regulation of different components of the epidermal growth factor receptor and Wnt/beta-catenin pathways and the down regulation of p14(ARF). The experimental approach described here should be applicable to other pathologies and neoplastic processes. PMID- 17848590 TI - Effects of automatic item eliminations based on item test analysis. AB - Item test analysis is an aid to identify items that need to be eliminated from an assessment. An automatic elimination procedure based on item statistics, therefore, could help to increase the quality of a test in an objective manner. This was investigated by studying the effect of a standardized elimination procedure on the test results of a second-year course over a period of 6 successive years in 1,624 candidates. Cohort effects on the item elimination were examined by determining the number of additional items that had to be eliminated from three different tests in 3 successive academic years in two cohorts. The items that were part of more than one test and had to be eliminated according to the procedure in at least one of the tests appeared to have to be retained according to the same procedure in most of the other tests. The procedure harmed the high scoring students relatively more often than the other students, and the number of eliminated items appeared to be cohort dependent. As a consequence, automatic elimination procedures obscure the transparency of the grading process unacceptably and transform valid tests into inadequate samples of the course content. PMID- 17848591 TI - Use of unsupervised online quizzes as formative assessment in a medical physiology course: effects of incentives on student participation and performance. AB - Online quizzes were introduced into a large Medical Physiology class to provide students with formative assessment before midterm and final summative examinations. Use of unsupervised online quizzes was chosen to provide a flexible supplementary learning tool for students without overwhelming a small faculty. Several quiz models were applied, which varied in the availability of course credit points for participation and performance. The aims of the study were to investigate if participation in formative assessment was associated with improved course outcomes, if offering incentives for completing quizzes affected student participation, and if quiz performance was predictive of summative examination outcomes. Results showed that students who elected to use online quizzes performed better in summative examinations. Offering course credit of between 0.5% and 2% per quiz increased student participation. However, evidence was found for widespread inappropriate use of unsupervised online quizzes when incentives for participation were applied. Predictive validity of online quizzes could be demonstrated when comparing the first of several quiz attempts with subsequent summative examination scores. PMID- 17848588 TI - A proteomics study of brassinosteroid response in Arabidopsis. AB - The plant steroid hormones brassinosteroids (BRs) play an important role in a wide range of developmental and physiological processes. How BR signaling regulates diverse processes remains unclear. To understand the molecular details of BR responses, we performed a proteomics study of BR-regulated proteins in Arabidopsis using two-dimensional DIGE coupled with LC-MS/MS. We identified 42 BR regulated proteins, which are predicted to play potential roles in BR regulation of specific cellular processes, such as signaling, cytoskeleton rearrangement, vesicle trafficking, and biosynthesis of hormones and vitamins. Analyses of the BR-insensitive mutant bri1-116 and BR-hypersensitive mutant bzr1-1D identified five proteins (PATL1, PATL2, THI1, AtMDAR3, and NADP-ME2) affected both by BR treatment and in the mutants, suggesting their importance in BR action. Selected proteins were further studied using insertion knock-out mutants or immunoblotting. Interestingly about 80% of the BR-responsive proteins were not identified in previous microarray studies, and direct comparison between protein and RNA changes in BR mutants revealed a very weak correlation. RT-PCR analysis of selected genes revealed gene-specific kinetic relationships between RNA and protein responses. Furthermore BR-regulated posttranslational modification of BiP2 protein was detected as spot shifts in two-dimensional DIGE. This study provides novel insights into the molecular networks that link BR signaling to specific cellular and physiological responses. PMID- 17848592 TI - The positive impact of team-based virtual microscopy on student learning in physiology and histology. AB - Team-based virtual microscopy and on-line learning were used to transform the first-year Physiology/Histology course at The Johns Hopkins School of Medicine into a student-centered learning environment. Prior to each laboratory session, students were required to view prelaboratory virtual lectures and examine digital slides that had been enhanced with annotations and 2-min microlectures. The laboratory classroom was then used for team-based learning exercises including student presentations and small-group discussions designed to integrate histology and physiology. The results of quantitative assessments indicated an 8- to 14 point increase over the identical final exams given over the past 5 yr. Means (+/ SD) of percent correct answers on the final exam were found to be 75.2% (11.1%), 72.5% (12.6%), 70.5% (12.6%), 73.6% (11.3%), 73.1% (12.2%), and 84.1% (9.1%) for years 2001-2006, respectively. The mean test scores for all other years were statistically lower compared with 2006, as determined by the Bonferroni post hoc multiple-comparison test (P < 0.001 for all years). PMID- 17848593 TI - Assessing core manipulative skills in a large, first-year laboratory. AB - Responding to the concern from our faculty that undergraduate students do not have robust laboratory skills, we designed and implemented a strategy to individually teach and assess the manipulative skills of students in first-year laboratories. Five core laboratory skills were selected for the course entitled Human Biology, a large, first-year class of students, most of whom were enrolled in Bachelor of Pharmacy and Human Movement Studies. Here, we report details for the 365 students enrolled primarily in Pharmacy and Human Movement Studies bachelor degree programs in semester 1 of 2006. We designed a specific strategy to assess five core laboratory skills: 1) accurate and precise use of a micropipette, 2) calculation of dilutions and preparation of diluted samples of saline, 3) accurate representation of data using a graph, 4) use of a light microscope, and 5) acquisition of digital data by measuring the latent period for the Achilles reflex. Graduate tutors were trained to teach and assess each student on each skill. The development of competency was tracked for all students across all five skills. Most students demonstrated proficiency on their first attempt. The development of proficiency across the core skills depended on both the skill and degree program. In semester 2 of 2006, 854 students mostly enrolled in the Bachelor of Science degree program and were similarly taught and assessed on the same five core skills. This approach was an effective teaching and assessment strategy that, when applied beyond first year, should increase the level of laboratory skills across undergraduate programs in physiology. PMID- 17848596 TI - "Challenge" questions to enhance laboratory experience and student skills: an example. AB - As educators, we are continually designing new methods and procedures to enhance learning. During this process, good ideas are frequently generated and tested, but the extent of such activities may not be adequate for a full manuscript. Nonetheless, the ideas may be quite beneficial in improving the teaching and learning of physiology. Illuminations is a column designed to facilitate the sharing of these ideas (illuminations). The format of the submissions is quite simple: a succinct description of about one or two double-spaced pages (less title and authorship) of something you have used for the classroom, teaching, laboratory, conference room, etc. You may include one or two simple figures or references. Submit ideas for inclusion in Illuminations directly to the Associate Editor in charge, Stephen DiCarlo (sdicarlo@med.wayne.edu). PMID- 17848594 TI - Adaptation to altitude as a vehicle for experiential learning of physiology by university undergraduates. AB - In this article, an experiential learning activity is described in which 19 university undergraduates made experimental observations on each other to explore physiological adaptations to high altitude. Following 2 wk of didactic sessions and baseline data collection at sea level, the group ascended to a research station at 12,500-ft elevation. Here, teams of three to four students measured the maximal rate of oxygen uptake, cognitive function, hand and foot volume changes, reticulocyte count and hematocrit, urinary pH and 24-h urine volume, athletic performance, and nocturnal blood oxygen saturation. Their data allowed the students to quantify the effect of altitude on the oxygen cascade and to demonstrate the following altitude-related changes: 1) impaired performance on selected cognitive function tests, 2) mild peripheral edema, 3) rapid reticulocytosis, 4) urinary alkalinization and diuresis, 5) impaired aerobic but not anaerobic exercise performance, 6) inverse relationship between blood oxygen saturation and resting heart rate, and 7) regular periodic nocturnal oxygen desaturation events accompanied by heart rate accelerations. The students learned and applied basic statistical techniques to analyze their data, and each team summarized its results in the format of a scientific paper. The students were uniformly enthusiastic about the use of self-directed experimentation to explore the physiology of altitude adaptation and felt that they learned more from this course format than a control group of students felt that they learned from a physiology course taught by the same instructor in the standard classroom/laboratory format. PMID- 17848598 TI - Aspirin enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in hormone-refractory prostate cancer cells through survivin down regulation. AB - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent because of its tumor selectivity. TRAIL is known to induce apoptosis in cancer cells but spare most normal cells. In this study, we examined whether acetylsalicylic acid (ASA), so-called aspirin, enhances TRAIL induced apoptosis in androgen-dependent LNCaP and androgen-independent LNCaP derived prostate cancer cells. To evaluate the cell death effects of TRAIL in combination with ASA on tumor cells, we performed DNA fragmentation assay and immunoblot analysis for poly(ADP-ribose) polymerase-1, caspases, and anti apoptotic proteins. We observed that ASA promoted TRAIL-induced apoptotic death in both LNCaP and its derived cells (C4, C4-2, and C4-2B). These enhancements of TRAIL's effect were related to the decrease in survivin protein expression by pretreatment with ASA. We also confirmed that knockdown in survivin expression by transfecting survivin small interfering RNA increased TRAIL-induced apoptosis. To study the mechanism of survivin down-regulation, we determined the levels of mRNA and the activities of survivin promoter in the ASA-treated and untreated cells. Reduction of the intracellular levels of survivin protein was due to a decrease in transcriptional activity. Data from electrophoretic mobility shift assay and chromatin immunoprecipitation analyses revealed that ASA inhibited the transcription factor E2F-1 binding activity to the survivin promoter region, which is known to regulate survivin gene transcription. Taken together, our studies suggested that ASA-promoted TRAIL cytotoxicity is mediated by down regulating survivin, and the down-regulation of survivin is due to inhibition of E2F-1 binding activity to the survivin promoter region. PMID- 17848599 TI - Transforming growth factor-beta 1 impairs endothelin-1-mediated contraction of brain vessels by inducing mitogen-activated protein (MAP) kinase phosphatase-1 and inhibiting p38 MAP kinase. AB - Brain levels of transforming growth factor-beta1 (TGF-beta1) are increased in Alzheimer's disease and have been implicated in the associated cerebrovascular pathology. We recently reported that transgenic mice that overexpress TGF-beta1 (TGF+ mice) display, with aging, selectively reduced endothelin-1 (ET-1)-mediated contractions. Because ET-1 is a key regulator of cerebrovascular tone and homeostasis, we investigated how increased levels of TGF-beta1 could selectively alter this contractile response. We found that ETA receptors, via activation of p38 mitogen-activated protein (MAP) kinase, mediate the ET-1-induced contraction in mouse cerebral arteries, a response significantly decreased in aged TGF+ mice (-39%; p < 0.01) despite unaltered ETA receptor levels or affinity. In cerebrovascular smooth muscle cell cultures, long-term treatment with TGF-beta1 significantly decreased (>50%; p < 0.05) the ET-1-induced activation of the p38 MAPK/27-kDa heat shock protein (HSP27) signaling pathway. This occurred with no effect upstream to p38 MAP kinase but with the concomitant induction of mitogen activated protein kinase phosphatase-1 (MKP-1) expression. Inhibition of MKP-1 expression with Ro-31-8220 or suppression of MKP-1 expression by short interfering RNA restored the ET-1-mediated p38 MAP kinase response. These results disclose a new role for long-term increases of TGF-beta1 in modulating cerebrovascular tone by dampening ET-1-mediated activation of the p38 MAPK/HSP27 signaling pathway. Such changes in ET-1-mediated signaling may help maintain vascular wall homeostasis by compensating for the diminished dilatory function induced by TGF-beta1 and amyloid-beta; brain levels of these two molecules are increased in patients with Alzheimer's disease. PMID- 17848600 TI - Mitochondria, calcium, and calpain are key mediators of resveratrol-induced apoptosis in breast cancer. AB - Resveratrol (RES), a natural plant polyphenol, has gained interest as a nontoxic chemopreventive agent capable of inducing tumor cell death in a variety of cancer types. However, the early molecular mechanisms of RES-induced apoptosis are not well defined. Using the human breast cancer cell lines MDA-MB-231 and MCF-7, we demonstrate that RES is antiproliferative and induces apoptosis in a concentration- and time-dependent manner. Preceding apoptosis, RES instigates a rapid dissipation of mitochondrial membrane potential by directly targeting mitochondria. This is followed by release of cytochrome c and second mitochondria derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) into the cytoplasm and substantial increase in the activities of caspases-9 and -3 in MDA-MB-231 cells. In addition, live cell microscopy demonstrates that RES causes an early biphasic increase in the concentration of free intracellular calcium ([Ca2+]i), probably resulting from depletion of the endoplasmic reticulum stores in breast cancer cells. In caspase 3-deficient MCF-7 cells, apoptosis is mediated by the Ca2+-activated protease, calpain, leading to the degradation of plasma membrane Ca2+-ATPase isoform 1 and fodrin; the degradation is attenuated by buffering [Ca2+]i and blocked by calpain inhibitors. Mitochondrial permeability transition pore antagonists also blocked calpain activation. In vivo mouse xenograft studies demonstrate that RES treatment inhibits breast cancer growth with no systemic toxicities. Together, these results suggest a critical role for mitochondria not only in the intrinsic apoptotic pathway but also in the Ca2+ and calpain-dependent cell death initiated by RES. Thus, RES may prove useful as a nontoxic alternative for breast cancer treatment. PMID- 17848601 TI - Roof and floor of the muscarinic binding pocket: variations in the binding modes of orthosteric ligands. AB - Alanine substitution mutagenesis has been used to investigate residues that make up the roof and floor of the muscarinic binding pocket and regulate ligand access. We mutated the amino acids in the second extracellular loop of the M1 muscarinic acetylcholine receptor that are homologous to the cis-retinal contact residues in rhodopsin, the disulfide-bonded Cys178 and Cys98 that anchor the loop to transmembrane helix 3, the adjoining acidic residue Asp99, and the conserved aromatic residues Phe197 and Trp378 in the transmembrane domain. The effects on ligand binding, kinetics, and receptor function suggest that the second extracellular loop does not provide primary contacts for orthosteric ligands, including acetylcholine, but that it does contribute to microdomains that are important for the conformational changes that accompany receptor activation. Kinetic studies suggest that the disulfide bond between Cys98 and Cys178 may contribute to structures that regulate the access of positively charged ligands such as N-methyl scopolamine to the binding pocket. Asp99 may act as a gatekeeper residue to this channel. In contrast, the bulkier lipophilic ligand 3 quinuclidinyl benzilate may require breathing motions of the receptor to access the binding site. Trp378 is a key residue for receptor activation as well as binding, whereas Phe197 represents the floor of the N-methyl scopolamine binding pocket but does not interact with acetylcholine or 3-quinuclidinyl benzilate. Differences between the binding modes of N-methyl scopolamine, 3-quinuclidinyl benzilate, and acetylcholine have been modeled. Although the head groups of these ligands occupy overlapping volumes within the binding site, their side chains may follow significantly different directions. PMID- 17848602 TI - microRNAs put their signatures on the heart. PMID- 17848603 TI - ACTN3 (R577X) genotype is associated with fiber type distribution. AB - alpha-Actinin-3 is a Z-disc structural protein found only in type II muscle fibers. The X allele of the R577X polymorphism in the ACTN3 gene results in a premature stop codon and alpha-actinin-3 deficiency in XX homozygotes. Associations between the R577X polymorphism and the muscle-power performance of elite athletes have been described earlier. About 45% of the fiber type proportions are determined by genetic factors. The ACTN3 variant could be one of the contributing genes in the heritability of fiber type distribution through its interaction with calcineurin. The aim of this study was to quantify the association between the polymorphism and muscle fiber type distribution and fast velocity knee extension strength. Ninety healthy young men (18-29 y) were genotyped for ACTN3 R577X. Knee extensor strength was measured isometrically (45 degrees ) and at different dynamic velocities (100-300 degrees /s) on a programmable dynamometer. Twenty-two XX and twenty-two RR subjects underwent a biopsy of the right vastus lateralis muscle. Fiber type composition was determined by immunohistochemistry. Homozygotes for the R allele show significantly higher relative dynamic quadriceps torques at 300 degrees /s, compared with XX carriers (P < 0.05). Fiber type characteristics differed significantly between the two genotype groups. The percentage surface and number of type IIx fibers were greater in the RR than the XX genotype group (P < 0.05), and alpha-actinin-3 protein content is systematically higher in type IIx compared with type IIa fibers (staining intensity ratio IIx to IIa = 1.17). This study shows that the mechanism, by which the ACTN3 polymorphism has its effect on muscle power, might rely on a control function of fiber type proportions. PMID- 17848604 TI - Influence of torpor on cardiac expression of genes involved in the circadian clock and protein turnover in the Siberian hamster (Phodopus sungorus). AB - The Siberian hamster exhibits the key winter adaptive strategy of daily torpor, during which metabolism and heart rate are slowed for a few hours and body temperature declines by up to 20 degrees C, allowing substantial energetic savings. Previous studies of hibernators in which temperature drops by >30 degrees C for many days to weeks have revealed decreased transcription and translation during hypometabolism and identified several key physiological pathways involved. Here we used a cDNA microarray to define cardiac transcript changes over the course of a daily torpor bout and return to normothermia, and we show that, in common with hibernators, a relatively small proportion of the transcriptome (<5%) exhibited altered expression over a torpor bout. Pathways exhibiting significantly altered gene expression included transcriptional regulation, RNA stability and translational control, globin regulation, and cardiomyocyte function. Remarkably, gene representatives of the entire ubiquitylation pathway were significantly altered over the torpor bout, implying a key role for cardiac protein turnover and translation during a low-temperature torpor bout. The circadian clock maintained rhythmic transcription during torpor. Quantitative PCR profiling of heart, liver, and lung and in situ hybridization studies of clock genes in the hypothalamic circadian clock in the suprachiasmatic nucleus revealed that many circadian regulated transcripts exhibited synchronous alteration in expression during arousal. Our data highlight the potential importance of genes involved in protein turnover as part of the adaptive strategy of low-temperature torpor in a seasonal mammal. PMID- 17848605 TI - Hepatic transcriptome response to glucocorticoid receptor activation in rainbow trout. AB - Cortisol, the principal corticosteroid in teleosts, is thought to play a key role in the metabolic adjustments critical for regaining homeostasis. However, the target tissue molecular mechanisms involved in this adaptive response to corticosteroid stimulation are still unclear. Cortisol signaling is mediated predominantly by the glucocorticoid receptor (GR), and previous studies have shown that RU486 (a GR antagonist) offsets corticosteroid signaling in teleosts. To elucidate the molecular basis of GR-mediated metabolic readjustments, we exposed primary culture of trout hepatocytes in vitro to cortisol (to mimic stressed levels seen in fish), RU486, or a combination of both for 24 h. The gene expression was analyzed using a low-density custom-made rainbow trout cDNA array enriched with endocrine-, metabolic-, and stress-related genes. The microarray results for select genes were further validated using quantitative real-time PCR. Cortisol treatment significantly increased glucose production in hepatocytes, and this response was blocked by RU486, confirming GR-mediated corticosteroid signaling. Cortisol also elevated GR transcript levels, and this response was abolished by RU486, whereas both cortisol and RU486, either alone or in combination, reduced GR protein content in trout hepatocytes. Cortisol treatment significantly modulated the expression of several genes known to be involved in intermediary metabolism, cellular stress response, reproduction, and xenobiotic metabolism. Most of these cortisol-mediated transcript changes were abolished in the presence of RU486, suggesting a key role for GR-specific signaling in this adaptive response. Taken together, our results suggest a key role for genomic cortisol signaling in the liver molecular reprogramming that is critical for coping with stress in fish. PMID- 17848606 TI - Identifying cis-regulatory elements by statistical analysis and phylogenetic footprinting and analyzing their coexistence and related gene ontology. AB - Discovery of cis-regulatory elements in gene promoters is a highly challenging research issue in computational molecular biology. This paper presents a novel approach to searching putative cis-regulatory elements in human promoters by first finding 8-mer sequences of high statistical significance from gene promoters of humans, mice, and Drosophila melanogaster, respectively, and then identifying the most conserved ones across the three species (phylogenetic footprinting). In this study, a conservation analysis on both closely related species (humans and mice) and distantly related species (humans/mice and Drosophila) is conducted not only to examine more candidates but also to improve the prediction accuracy. We have found 124 putative cis-regulatory elements and grouped these into 20 clusters. The investigation on the coexistence of these clusters in human gene promoters reveals that SP1, EGR, and NRF-1 are the dominant clusters appearing in the combinatorial combination of up to five clusters. Gene Ontology (GO) analysis also shows that many GO categories of transcription factors binding to these cis-regulatory elements match the GO categories of genes whose promoters contain these elements. Compared with previous research, the contribution of this study lies not only in the finding of new cis-regulatory elements, but also in its pioneering exploration on the coexistence of discovered elements and the GO relationship between transcription factors and regulated genes. This exploration verifies the putative cis regulatory elements that have been found from this study and also gives new insight on the regulation mechanisms of gene expression. PMID- 17848607 TI - Macrophage-mediated neuroprotection and neurogenesis in the olfactory epithelium. AB - Resident and recruited olfactory epithelial macrophages participate in the regulation of the survival, degeneration, and replacement of olfactory sensory neurons (OSNs). We have reported that liposome-encapsulated clodronate (Lip-C) induced selective and statistically significant depletion of macrophages in the OE of sham and 48 h OBX mice (38 and 35%, respectively) that resulted in increased OSN apoptosis and decreased numbers of mature OSNs and proliferating basal cells compared to controls (Lip-O). The aim of this study was to identify molecular mechanisms by which the selective depletion of macrophages in the OE resulted in these cellular changes by using a microarray expression pattern analysis. A 2x2 ANOVA identified 4,085 overall significantly (P < 0.01) regulated genes in the OE of Lip-O and Lip-C sham and 48 h OBX mice, and further statistical analysis using pairwise comparisons identified 4,024 genes that had either a significant (P < 0.01) treatment main effect (n = 2,680), group main effect (n = 778), or interaction effect (n = 980). The mean hybridization signals of immune response genes, e.g., Cxcr4, and genes encoding growth factors and neurogenesis regulators, e.g., Hdgf and Neurod1, respectively, were primarily lower in Lip-C mice compared with Lip-O mice. Apoptosis genes, e.g., Bak1, were also differentially regulated in Lip-C and/or OBX mice. Expression patterns of selected genes were validated with real-time RT-PCR; immunohistochemistry was used to localize selected gene products. These results identified the differential regulation of several novel genes through which alternatively activated macrophages regulate OSN progenitor cell proliferation, differentiation, and maturation, and the survival of OSNs. PMID- 17848608 TI - Continuous home monitoring of glucose: improved glycemic control with real-life use of continuous glucose sensors in adult subjects with type 1 diabetes. PMID- 17848609 TI - Glycemic effects of moderate alcohol intake among patients with type 2 diabetes: a multicenter, randomized, clinical intervention trial. AB - OBJECTIVE: In a randomized controlled trial, we assessed the effect of daily moderate alcohol intake on glycemic control in the fasting and postprandial states in patients with type 2 diabetes who previously had abstained from alcohol. RESEARCH DESIGN AND METHODS: We randomly assigned 109 patients (41-74 years old) with established type 2 diabetes who abstained from alcohol to receive 150 ml wine (13 g alcohol) or nonalcoholic diet beer (control) each day during a 3-month multicenter trial. The beverages were consumed during dinner. Diet and alcohol consumption were monitored. RESULTS: During the intervention, 17% of participants (12% from the alcohol group) dropped out, leaving 91 who completed the trial. Within the alcohol group, fasting plasma glucose (FPG) decreased from 139.6 +/- 41 to 118.0 +/- 32.5 mg/dl after 3 months compared with 136.7 +/- 15.4 to 138.6 +/- 27.8 mg/dl in the control subjects (P(v) = 0.015). However, alcohol consumption had no effect on 2-h postprandial glucose levels (difference of 18.5 mg/dl in the control group vs. 17.7 mg/dl in the alcohol group, P(v) = 0.97). Patients in the alcohol group with higher baseline A1C levels had greater reductions in FPG (age-adjusted correlation -0.57, P(v) < 0.001). No significant changes were observed in the levels of bilirubin, alkaline phosphatase, alanine aminotransferase, or aspartate aminotransferase, and no notable adverse effects were reported. Participants in the alcohol group reported an improvement in the ability to fall asleep (P(v) < 0.001). CONCLUSIONS: Among patients with type 2 diabetes who had previously abstained from alcohol, initiation of moderate daily alcohol consumption reduced FPG but not postprandial glucose. Patients with higher A1C may benefit more from the favorable glycemic effect of alcohol. Further intervention studies are needed to confirm the long-term effect of moderate alcohol intake. PMID- 17848610 TI - Incidences, treatments, outcomes, and sex effect on survival in patients with end stage renal disease by diabetes status in Australia and New Zealand (1991 2005). AB - OBJECTIVE: We aimed to update the epidemiology of type 1 and type 2 diabetic patients among the incident end-stage renal disease (ESRD) population in Australia and New Zealand (ANZ) and to determine whether outcome is worse for diabetic women, as described in the general population. RESEARCH DESIGNS AND METHODS: All resident adults of ANZ who began renal replacement therapy (RRT) from 1 April 1991 to 31 December 2005 were included using data from the ANZ Dialysis and Transplant Registry. Incidence rates, RRT, and survival were analyzed. Risk factors for death were assessed using Cox regression. RESULTS: The study included 1,284 type 1 diabetic (4.5%), 8,560 type 2 diabetic (30.0%), and 18,704 nondiabetic (65.5%) patients. The incidence rate of ESRD with type 2 diabetes increased markedly over time (+10.2% annually, P < 0.0001). In patients aged <70 years, rates of renal transplantation in type 1 diabetic, type 2 diabetic, and nondiabetic patients were 41.8, 6.5 (P < 0.0001 vs. other patients), and 40.9% (P = 0.56 vs. type 1 diabetic patients), respectively. Compared with nondiabetic patients, the adjusted hazard ratio (HR) for death was 1.64 (P < 0.0001) in type 1 diabetes and 1.13 (P < 0.0001) in type 2 diabetes. Survival rates per 5-year period improved by 6% in type 1 diabetic patients (P = 0.36), by 9% in type 2 diabetic patients (P < 0.0001), and by 5% in nondiabetic patients (P = 0.001). In type 2 diabetic patients aged >or=60 years, the adjusted HR for death in women versus men was 1.19 (P = 0.0003). CONCLUSIONS: The incidence of ESRD with type 2 diabetes increased markedly. Despite high access to renal transplants, type 1 diabetic patients had a poor prognosis after starting RRT. Survival improved significantly in type 2 diabetic patients during the study period. Older type 2 diabetic women had a worse prognosis than older type 2 diabetic men. PMID- 17848611 TI - Diabetes, the metabolic syndrome, and ischemic stroke: epidemiology and possible mechanisms. PMID- 17848612 TI - Targeting glucose in acute myocardial infarction: has glucose, insulin, and potassium infusion missed the target? PMID- 17848613 TI - C-reactive protein in diabetic and nondiabetic patients with acute myocardial infarction. PMID- 17848614 TI - Metabolic syndrome and incident end-stage peripheral vascular disease: a 14-year follow-up study in elderly Finns. AB - OBJECTIVE: We investigated the relationship of the metabolic syndrome and its single components, defined by four different criteria, with peripheral vascular disease (PVD) in a prospective population-based study. RESEARCH DESIGN AND METHODS: The metabolic syndrome was defined according to the World Health Organization (WHO), the National Cholesterol Education Program (NCEP), the International Diabetes Federation (IDF), and the American Heart Association (updated NCEP) criteria. We investigated the relationship of the metabolic syndrome defined by the aforementioned four criteria with PVD (revacularization and amputation) by Cox regression analyses in a Finnish population of 1,212 subjects, aged 65-74 years, with and without diabetes during a 14-year follow-up. RESULTS: The metabolic syndrome defined by the WHO, NCEP, and updated NCEP criteria was associated with a statistically significant risk for incident PVD (n = 57) with adjustment for all confounding variables except for prevalent diabetes (hazard ratios [HRs] from 1.91 to 2.62). After adjustment for prevalent diabetes or after the exclusion of subjects with prevalent diabetes, there was no association between the metabolic syndrome by any criteria and incident PVD. Of the single components of the metabolic syndrome, elevated fasting glucose by the WHO and NCEP criteria (HR 2.35) and microalbuminuria by the WHO definition (2.56) predicted PVD in multivariable models (prevalent diabetes included). CONCLUSIONS: The metabolic syndrome defined by the WHO, NCEP, and updated NCEP criteria predicted incident end-stage PVD in elderly Finns but only when not adjusted for diabetes status. Two of the single components of the metabolic syndrome, elevated fasting plasma glucose and microalbuminuria, predicted PVD. We conclude that the metabolic syndrome predicts PVD but not above and beyond the risk associated with diabetes and microalbuminuria. PMID- 17848615 TI - Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non ST-elevation acute coronary syndrome. AB - BACKGROUND: An invasive treatment strategy improves outcome in patients with non ST-elevation acute coronary syndrome at moderate to high risk. We hypothesized that the circulating level of growth differentiation factor 15 (GDF-15) may improve risk stratification. METHODS AND RESULTS: The Fast Revascularization during InStability in Coronary artery disease II (FRISC-II) trial randomized patients with non-ST-elevation acute coronary syndrome to an invasive or conservative strategy with a follow-up for 2 years. GDF-15 and other biomarkers were determined on admission in 2079 patients. GDF-15 was moderately elevated (between 1200 and 1800 ng/L) in 770 patients (37.0%), and highly elevated (>1800 ng/L) in 493 patients (23.7%). Elevated levels of GDF-15 independently predicted the risk of the composite end point of death or recurrent myocardial infarction in the conservative group (P=0.016) but not in the invasive group. A significant interaction existed between the GDF-15 level on admission and the effect of treatment strategy on the composite end point. The occurrence of the composite end point was reduced by the invasive strategy at GDF-15 levels >1800 ng/L (hazard ratio, 0.49; 95% confidence interval, 0.33 to 0.73; P=0.001), between 1200 and 1800 ng/L (hazard ratio, 0.68; 95% confidence interval, 0.46 to 1.00; P=0.048), but not <1200 ng/L (hazard ratio, 1.06; 95% confidence interval, 0.68 to 1.65; P=0.81). Patients with ST-segment depression or a troponin T level >0.01 microg/L with a GDF-15 level <1200 ng/L did not benefit from the invasive strategy. CONCLUSIONS: GDF-15 is a potential tool for risk stratification and therapeutic decision making in patients with non-ST-elevation acute coronary syndrome as initially diagnosed by ECG and troponin levels. A prospective randomized trial is needed to validate these findings. PMID- 17848616 TI - Determinants of PF4/heparin immunogenicity. AB - Heparin-induced thrombocytopenia (HIT) is an antibody-mediated disorder that occurs with variable frequency in patients exposed to heparin. HIT antibodies preferentially recognize large macromolecular complexes formed between PF4 and heparin over a narrow range of molar ratios, but the biophysical properties of complexes that initiate antibody production are unknown. To identify structural determinants underlying PF4/heparin immunogenicity, we characterized the in vitro interactions of murine PF4 (mPF4) and heparin with respect to light absorption, size, and surface charge (zeta potential). We show that PF4/heparin macromolecular assembly occurs through colloidal interactions, wherein heparin facilitates the growth of complexes through charge neutralization. The size of PF4/heparin macromolecules is governed by the molar ratios of the reactants. Maximal complex size occurs at molar ratios of PF4/heparin at which surface charge is neutral. When mice are immunized with complexes that differ in size and/or zeta potential, antibody formation varies inversely with heparin concentration and is most robust in animals immunized with complexes displaying a net positive zeta-potential. These studies suggest that the clinical heterogeneity in the HIT immune response may be due in part to requirements for specific biophysical parameters of the PF4/heparin complexes that occur in settings of intense platelet activation and PF4 release. PMID- 17848617 TI - Antihuman factor VIII C2 domain antibodies in hemophilia A mice recognize a functionally complex continuous spectrum of epitopes dominated by inhibitors of factor VIII activation. AB - The diversity of factor VIII (fVIII) C2 domain antibody epitopes was investigated by competition enzyme-linked immunosorbent assay (ELISA) using a panel of 56 antibodies. The overlap patterns produced 5 groups of monoclonal antibodies (MAbs), designated A, AB, B, BC, and C, and yielded a set of 18 distinct epitopes. Group-specific loss of antigenicity was associated with mutations at the Met2199/Phe2200 phospholipid binding beta-hairpin (group AB MAbs) and at Lys2227 (group BC MAbs), which allowed orientation of the epitope structure as a continuum that covers one face of the C2 beta-sandwich. MAbs from groups A, AB, and B inhibit the binding of fVIIIa to phospholipid membranes. Group BC was the most common group and displayed the highest specific fVIII inhibitor activities. MAbs in this group are type II inhibitors that inhibit the activation of fVIII by either thrombin or factor Xa and poorly inhibit the binding of fVIII to phospholipid membranes or von Willebrand factor (VWF). Group BC MAbs are epitopically and mechanistically distinct from the extensively studied group C MAb, ESH8. These results reveal the structural and functional complexity of the anti-C2 domain antibody response and indicate that interference with fVIII activation is a major attribute of the inhibitor landscape. PMID- 17848618 TI - The new tumor-suppressor gene inhibitor of growth family member 4 (ING4) regulates the production of proangiogenic molecules by myeloma cells and suppresses hypoxia-inducible factor-1 alpha (HIF-1alpha) activity: involvement in myeloma-induced angiogenesis. AB - Angiogenesis has a critical role in the pathophysiology of multiple myeloma (MM); however, the molecular mechanisms underlying this process are not completely elucidated. The new tumor-suppressor gene inhibitor of growth family member 4 (ING4) has been recently implicated in solid tumors as a repressor of angiogenesis. In this study, we found that ING4 expression in MM cells was correlated with the expression of the proangiogenic molecules interleukin-8 (IL 8) and osteopontin (OPN). Moreover, we demonstrate that ING4 suppression in MM cells up-regulated IL-8 and OPN, increasing the hypoxia inducible factor-1alpha (HIF-1alpha) activity and its target gene NIP-3 expression in hypoxic condition. In turn, we show that the inhibition of HIF-1alpha by siRNA suppressed IL-8 and OPN production by MM cells under hypoxia. A direct interaction between ING4 and the HIF prolyl hydroxylase 2 (HPH-2) was also demonstrated. Finally, we show that ING4 suppression in MM cells significantly increased vessel formation in vitro, blunted by blocking IL-8 or OPN. These in vitro observations were confirmed in vivo by finding that MM patients with high IL-8 production and microvascular density (MVD) have significantly lower ING4 levels compared with those with low IL-8 and MVD. Our data indicate that ING4 exerts an inhibitory effect on the production of proangiogenic molecules and consequently on MM-induced angiogenesis. PMID- 17848619 TI - Tumor-associated leukemia inhibitory factor and IL-6 skew monocyte differentiation into tumor-associated macrophage-like cells. AB - Tumor-associated macrophages (TAMs), the most abundant immunosuppressive cells in the tumor microenvironment, originate from blood monocytes and exhibit an IL 10(high)IL-12(low) M2 profile. The factors involved in TAM generation remain unidentified. We identify here leukemia inhibitory factor (LIF) and IL-6 as tumor microenvironmental factors that can promote TAM generation. Ovarian cancer ascites switched monocyte differentiation into TAM-like cells that exhibit most ovarian TAM functional and phenotypic characteristics. Ovarian cancer ascites contained high concentrations of LIF and IL-6. Recombinant LIF and IL-6 skew monocyte differentiation into TAM-like cells by enabling monocytes to consume monocyte-colony-stimulating factor (M-CSF). Depletion of LIF, IL-6, and M-CSF in ovarian cancer ascites suppressed TAM-like cell induction. We extended these observations to different tumor-cell line supernatants. In addition to revealing a new tumor-escape mechanism associated with TAM generation via LIF and IL-6, these findings offer novel therapeutic perspectives to subvert TAM-induced immunosuppression and hence improve T-cell-based antitumor immunotherapy efficacy. PMID- 17848620 TI - Dual ITAM-mediated proteolytic pathways for irreversible inactivation of platelet receptors: de-ITAM-izing FcgammaRIIa. AB - Collagen binding to glycoprotein VI (GPVI) induces signals critical for platelet activation in thrombosis. Both ligand-induced GPVI signaling through its coassociated Fc-receptor gamma-chain (FcRgamma) immunoreceptor tyrosine activation motif (ITAM) and the calmodulin inhibitor, W7, dissociate calmodulin from GPVI and induce metalloproteinase-mediated GPVI ectodomain shedding. We investigated whether signaling by another ITAM-bearing receptor on platelets, FcgammaRIIa, also down-regulates GPVI expression. Agonists that signal through FcgammaRIIa, the mAbs VM58 or 14A2, potently induced GPVI shedding, inhibitable by the metalloproteinase inhibitor, GM6001. Unexpectedly, FcgammaRIIa also underwent rapid proteolysis in platelets treated with agonists for FcgammaRIIa (VM58/14A2) or GPVI/FcRgamma (the snake toxin, convulxin), generating an approximate 30-kDa fragment. Immunoprecipitation/pull-down experiments showed that FcgammaRIIa also bound calmodulin and W7 induced FcgammaRIIa cleavage. However, unlike GPVI, the approximate 30-kDa FcgammaRIIa fragment remained platelet associated, and proteolysis was unaffected by GM6001 but was inhibited by a membrane-permeable calpain inhibitor, E64d; consistent with this, micro calpain cleaved an FcgammaRIIa tail-fusion protein at (222)Lys/(223)Ala and (230)Gly/(231)Arg, upstream of the ITAM domain. These findings suggest simultaneous activation of distinct extracellular (metalloproteinase-mediated) and intracellular (calpain-mediated) proteolytic pathways irreversibly inactivating platelet GPVI/FcRgamma and FcgammaRIIa, respectively. Activation of both pathways was observed with immunoglobulin from patients with heparin-induced thrombocytopenia (HIT), suggesting novel mechanisms for platelet dysfunction by FcgammaRIIa after immunologic insult. PMID- 17848621 TI - Erythrocyte glutamine depletion, altered redox environment, and pulmonary hypertension in sickle cell disease. AB - Erythrocyte glutathione depletion has been linked to hemolysis and oxidative stress. Glutamine plays an additional antioxidant role through preservation of intracellular nicotinamide adenine dinucleotide phosphate (NADPH) levels, required for glutathione recycling. Decreased nitric oxide (NO) bioavailability, which occurs in the setting of increased hemolysis and oxidative stress, contributes to the pathogenesis of pulmonary hypertension (PH) in sickle cell disease (SCD). We hypothesized that altered glutathione and glutamine metabolism play a role in this process. Total glutathione (and its precursors) and glutamine were assayed in plasma and erythrocytes of 40 SCD patients and 9 healthy volunteers. Erythrocyte total glutathione and glutamine levels were significantly lower in SCD patients than in healthy volunteers. Glutamine depletion was independently associated with PH, defined as a tricuspid regurgitant jet velocity (TRV) of at least 2.5 m/s. The ratio of erythrocyte glutamine:glutamate correlated inversely to TRV (r = -0.62, P < .001), plasma arginase concentration (r = -0.45, P = .002), and plasma-free hemoglobin level (r = -0.41, P = .01), linking erythrocyte glutamine depletion to dysregulation of the arginine-NO pathway and increased hemolytic rate. Decreased erythrocyte glutathione and glutamine levels contribute to alterations in the erythrocyte redox environment, which may compromise erythrocyte integrity, contribute to hemolysis, and play a role in the pathogenesis of PH of SCD. PMID- 17848622 TI - Involvement of xeroderma pigmentosum group A (XPA) in progeria arising from defective maturation of prelamin A. AB - Cellular accumulation of DNA damage has been widely implicated in cellular senescence, aging, and premature aging. In Hutchinson-Gilford progeria syndrome (HGPS) and restrictive dermopathy (RD), premature aging is linked to accumulation of DNA double-strand breaks (DSBs), which results in genome instability. However, how DSBs accumulate in cells despite the presence of intact DNA repair proteins remains unknown. Here we report that the recruitment of DSB repair factors Rad50 and Rad51 to the DSB sites, as marked by gamma-H2AX, was impaired in human HGPS and Zmpste24-deficient cells. Consistently, the progeria-associated DSBs appeared to be unrepairable although DSBs induced by camptothecin were efficiently removed in the progeroid cells. We also found that these progeroid cells exhibited nuclear foci of xeroderma pigmentosum group A (XPA), a unique nucleotide excision repair protein. Strikingly, these XPA foci colocalized with the DSB sites in the progeroid cells. This XPA-DSB association was further confirmed and found to be mediated by DNA, using a modified chromatin immunoprecipitation assay and coimmunoprecipitation. RNA interference (RNAi) knockdown of XPA in HGPS cells partially restored DSB repair as evidenced by Western blot analysis, immunofluorescence and comet assays. We propose that the uncharacteristic localization of XPA to or near DSBs inhibits DSB repair, thereby contributing to the premature aging phenotypes observed in progeria arising from genetic defects in prelamin A maturation. PMID- 17848623 TI - Circulating progenitor cells contribute to neointimal formation in nonirradiated chimeric mice. AB - Recent evidence suggests that bone marrow-derived cells may contribute to repair and lesion formation following vascular injury. In most studies, bone marrow derived cells were tracked by transplanting exogenous cells into bone marrow that had been compromised by irradiation. It remains to be determined whether endogenous circulating progenitors actually contribute to arterial remodeling under physiological conditions. Here, we established a parabiotic model in which two mice were conjoined subcutaneously without any vascular anastomosis. When wild-type mice were joined with transgenic mice that expressed green fluorescent protein (GFP) in all tissues, GFP-positive cells were detected not only in the peripheral blood but also in the bone marrow of the wild-type mice. The femoral arteries of the wild-type mice were mechanically injured by insertion of a large wire. At 4 wk, there was neointima hyperplasia that mainly consisted of alpha smooth muscle actin-positive cells. GFP-positive cells were readily detected in the neointima (14.8+/-4.5%) and media (31.1+/-8.8%) of the injured artery. Some GFP-positive cells expressed alpha-smooth muscle actin or an endothelial cell marker. These results indicate that circulating progenitors contribute to re endothelialization and neointimal formation after mechanical vascular injury even in nonirradiated mice. PMID- 17848624 TI - Adipocyte death, adipose tissue remodeling, and obesity complications. AB - OBJECTIVE: We sought to determine the role of adipocyte death in obesity-induced adipose tissue (AT) inflammation and obesity complications. RESEARCH DESIGN AND METHODS: Male C57BL/6 mice were fed a high-fat diet for 20 weeks to induce obesity. Every 4 weeks, insulin resistance was assessed by intraperitoneal insulin tolerance tests, and epididymal (eAT) and inguinal subcutaneous AT (iAT) and livers were harvested for histological, immunohistochemical, and gene expression analyses. RESULTS: Frequency of adipocyte death in eAT increased from <0.1% at baseline to 16% at week 12, coincident with increases in 1) depot weight; 2) AT macrophages (ATM Phi s) expressing F4/80 and CD11c; 3) mRNA for tumor necrosis factor (TNF)-alpha, monocyte chemotactic protein (MCP)-1, and interleukin (IL)-10; and 4) insulin resistance. ATM Phi s in crown-like structures surrounding dead adipocytes expressed TNF-alpha and IL-6 proteins. Adipocyte number began to decline at week 12. At week 16, adipocyte death reached approximately 80%, coincident with maximal expression of CD11c and inflammatory genes, loss (40%) of eAT mass, widespread collagen deposition, and accelerated hepatic macrosteatosis. By week 20, adipocyte number was restored with small adipocytes, coincident with reduced adipocyte death (fourfold), CD11c and MCP-1 gene expression (twofold), and insulin resistance (35%). eAT weight did not increase at week 20 and was inversely correlated with liver weight after week 12 (r = -0. 85, P < 0.001). In iAT, adipocyte death was first detected at week 12 and remained 90%; Pincus SM, Hartman ML, Roelfsema F, Thorner MO, Veldhuis JD. Am J Physiol Endocrinol Metab 273: E948-E957, 1999). A time-incremented moving window of ApEn was applied to LH time series obtained by intensive (10-min) blood sampling for four consecutive days (577 successive measurements) in each of eight healthy men. Analyses unveiled marked 24-h variations in ApEn with daily maxima (lowest feedback) at 1100 +/- 1.7 h (mean +/- SE) and minima (highest feedback) at 0430 +/- 1.9 h. The mean difference between maximal and minimal 24-h LH ApEn was 0.348 +/- 0.018, which differed by P < 0.001 from all three of randomly shuffled versions of the same LH time series, simulated pulsatile data and assay noise. Analyses artificially limited to 24-h rather than 96-h data yielded reproducibility coefficients of 3.7-9.0% for ApEn maxima and minima. In conclusion, a feedback sensitive regularity statistic unmasks strong and consistent 24-h rhythmicity of the orderliness of unperturbed pituitary-hormone secretion. These outcomes suggest that ApEn may have general utility in probing dynamic mechanisms mediating feedback in other endocrine systems. PMID- 17848634 TI - Adenine nucleotides decrease the apparent Km of endogenous natriuretic peptide receptors for GTP. AB - Natriuretic peptide receptors A (NPR-A) and B (NPR-B) mediate most effects of natriuretic peptides by synthesizing cGMP. ATP increases the activity of these receptors by an unknown mechanism. We recently reported that a nonhydrolyzable form of ATP, adenylyl imidodiphosphate (AMPPNP), stabilizes but is not required for the activation of NPR-A and NPR-B in membranes from highly overexpressing cells. Here, we repeated these studies on receptors expressed in endogenous settings. Kinetic analysis indicated that both AMPPNP and ATP dramatically decrease the apparent K(m) of both receptors for GTP but had little effect on the V(max). The EC(50) for AMPPNP decreased as substrate concentration increased whereas the magnitude of the effect was greater at lower GTP concentrations. ATP increased the activity of a mutant receptor containing glutamates substituted for all known phosphorylation sites similarly to the wild-type receptor, consistent with a phosphorylation independent mechanism. Finally, the putative ATP binding sites were investigated. Mutation of the ATP modulatory domain region had no effect, but mutation of K535A dramatically diminished ANP-dependent cyclase activity in a manner that was unresponsive to ATP. Mutation of the highly conserved 630-KSS to AAA (all alanines) resulted in an expressed receptor that had no detectable guanylyl cyclase activity. We conclude that ATP is not required for the initial activation of NPRs but does increase activity over time by reducing the apparent K(m) for GTP. PMID- 17848635 TI - Fibroblast growth factor-2 in hyperplastic pituitaries of D2R knockout female mice. AB - Dopamine D2 receptor (D2R) knockout (KO) female mice develop chronic hyperprolactinemia and pituitary hyperplasia. Our objective was to study the expression of the mitogen fibroblast growth factor (FGF2) and its receptor, FGFR1, comparatively in pituitaries from KO and wild-type (WT) female mice. We also evaluated FGF2 subcellular localization and FGF2 effects on pituitary function. FGF2-induced prolactin release showed a similar response pattern in both genotypes, even though basal and FGF2-stimulated release was higher in KO. FGF2 stimulated pituitary cellular proliferation (MTS assay and [(3)H]thymidine incorporation), with no differences between genotypes. FGF2 concentration (measured by ELISA) in whole pituitaries or cultured cells was lower in KO (P < 0.00001 and 0.00014). Immunofluorescence histochemistry showed less FGF2 in pituitaries from KO females and revealed a distinct FGF2 localization pattern between genotypes, being predominantly nuclear in KO and cytosolic in WT pituitaries. Finally, FGF2 could not be detected in the conditioned media from pituitary cultures of both genotypes. FGFR1 levels (Western blot and immunohistochemistry) were higher in pituitaries of KO. Basal concentration of phosphorylated ERKs was lower in KO cells (P = 0.018). However, when stimulated with FGF2, a significantly higher increment of ERK phosphorylation was evidenced in KO cells (P < or = 0.02). We conclude that disruption of the D2R caused an overall decrease in pituitary FGF2 levels, with an increased distribution in the nucleus, and increased FGFR1 levels. These results are important in the search for reliable prognostic indicators for patients with pituitary dopamine-resistant prolactinomas, which will make tumor-specific therapy possible. PMID- 17848636 TI - Modulation of expression of somatostatin receptor subtypes in Graves' ophthalmopathy orbits: relevance to novel analogs. AB - Apart from evaluating orbital inflammation in Graves' ophthalmopathy (GO), somatostatin (SST) analogs have been proposed as a therapy, but recent trials were disappointing. We aimed to measure somatostatin receptor (SSTR) expression in orbital tissues ex vivo and determine whether the new broad-affinity analog SOM230 might be of therapeutic use. Orbital adipose/connective tissues from 29 GO patients and 10 normal individuals were analyzed. Transcripts were quantified using SYBR Green and a light cycler. In vitro models were used to investigate whether thyrotropin receptor activation (as occurs via thyroid stimulating antibodies) or adipogenesis affected SSTR expression in primary preadipocytes and to compare the biological activity of octreotide and SOM230 in their modulation. The expression of SSTR1 was significantly higher in GO patients than normal controls (P = 0.024). Although differences in the expression of SSTR2 were not significant, 39% of GO samples had levels above the 97th percentile of the controls. SSTR3, -4, and -5 were at or below the limit of detection (LOD). The lymphocyte contribution was minimal, since CD3alpha transcripts were at the LOD. TSH receptor activation did not modulate SSTR expression. An in vitro model of adipogenesis indicated upregulation of SSTR1 and SSTR2 during differentiation. SOM230 produced significantly greater inhibition of orbital preadipocyte proliferation than octreotide. Ex vivo analysis of orbital tissues reveals upregulation of SSTR1 and -2 in a group of GO patients. Adipogenesis, a process occurring in GO orbits, provides one possible explanation for some of the observed increase. PMID- 17848637 TI - Amino acids augment muscle protein synthesis in neonatal pigs during acute endotoxemia by stimulating mTOR-dependent translation initiation. AB - In skeletal muscle of adults, sepsis reduces protein synthesis by depressing translation initiation and induces resistance to branched-chain amino acid stimulation. Normal neonates maintain a high basal muscle protein synthesis rate that is sensitive to amino acid stimulation. In the present study, we determined the effect of amino acids on protein synthesis in skeletal muscle and other tissues in septic neonates. Overnight-fasted neonatal pigs were infused with endotoxin (LPS, 0 and 10 microg.kg(-1).h(-1)), whereas glucose and insulin were maintained at fasting levels; amino acids were clamped at fasting or fed levels. In the presence of fasting insulin and amino acids, LPS reduced protein synthesis in longissimus dorsi (LD) and gastrocnemius muscles and increased protein synthesis in the diaphragm, but had no effect in masseter and heart muscles. Increasing amino acids to fed levels accelerated muscle protein synthesis in LD, gastrocnemius, masseter, and diaphragm. LPS stimulated protein synthesis in liver, lung, spleen, pancreas, and kidney in fasted animals. Raising amino acids to fed levels increased protein synthesis in liver of controls, but not LPS treated animals. The increase in muscle protein synthesis in response to amino acids was associated with increased mTOR, 4E-BP1, and S6K1 phosphorylation and eIF4G-eIF4E association in control and LPS-infused animals. These findings suggest that amino acids stimulate skeletal muscle protein synthesis during acute endotoxemia via mTOR-dependent ribosomal assembly despite reduced basal protein synthesis rates in neonatal pigs. However, provision of amino acids does not further enhance the LPS-induced increase in liver protein synthesis. PMID- 17848639 TI - Patent prosecution strategies for stem cell related applications. AB - Stem cell research and the intellectual property derived from it, because of its potential to completely transform health care, demand an especially high level of consideration from business and patent prosecution perspectives. As with other revolutionary technologies, ordinary risks are amplified (e.g., litigation), and ordinarily irrelevant considerations may become important (e.g., heightened level of both domestic and foreign legislative risk). In the first part of this article, general strategies for patent prosecutors such as several prosecution considerations and methods for accelerating patent prosecution process are presented. In the second part, patent prosecution challenges of stem cell-related patents and possible solutions are discussed. In the final part, ethical and public policy issues particular to stem cell-related and other biotechnological inventions are summarized. PMID- 17848640 TI - A multipumping flow system for in vitro screening of peroxynitrite scavengers. AB - Peroxynitrite anion is a reactive nitrogen species formed in vivo by the rapid, controlled diffusion reaction between nitric oxide and superoxide radicals. By reacting with several biological molecules, peroxynitrite may cause important cellular and tissue deleterious effects, which have been associated with many diseases. In this work, an automated flow-based procedure for the in vitro generation of peroxynitrite and subsequent screening of the scavenging activity of selected compounds is developed. This procedure involves a multipumping flow system (MPFS) and exploits the ability of compounds such as lipoic acid, dihydrolipoic acid, cysteine, reduced glutathione, oxidized glutathione, sulindac, and sulindac sulfone to inhibit the chemiluminescent reaction of luminol with peroxynitrite under physiological simulated conditions. Peroxynitrite was generated in the MPFS by the online reaction of acidified hydrogen peroxide with nitrite, followed by a subsequent stabilization by merging with a sodium hydroxide solution to rapidly quench the developing reaction. The pulsed flow and the timed synchronized insertion of sample and reagent solutions provided by the MPFS ensure the establishment of the reaction zone only inside the flow cell, thus allowing maximum chemiluminescence emission detection. The results obtained for the assayed compounds show that, with the exception of oxidized glutathione, all are highly potent scavengers of peroxynitrite at the studied concentrations. PMID- 17848638 TI - PPARgamma regulates adipose triglyceride lipase in adipocytes in vitro and in vivo. AB - Peroxisome proliferator-activated receptor-gamma (PPARgamma) regulates adipocyte genes involved in adipogenesis and lipid metabolism and is the molecular target for thiazolidinedione (TZD) antidiabetic agents. Adipose triglyceride lipase (ATGL) is a recently described triglyceride-specific lipase that is induced during adipogenesis and remains highly expressed in mature adipocytes. This study evaluates the ability of PPARgamma to directly regulate ATGL expression in adipocytes in vitro and in vivo. In fully differentiated 3T3-L1 adipocytes, ATGL mRNA and protein are increased by TZD and non-TZD PPARgamma agonists in a dose- and time-dependent manner. Rosiglitazone-mediated induction of ATGL mRNA is rapid and is not inhibited by the protein synthesis inhibitor cycloheximide, indicating that intervening protein synthesis is not required for this effect. Rosiglitazone mediated induction of ATGL mRNA and protein is inhibited by the PPARgamma specific antagonist GW-9662 and is also significantly reduced following siRNA mediated knockdown of PPARgamma, supporting the direct transcriptional regulation of ATGL by PPARgamma. In vivo, ATGL mRNA and protein are increased by rosiglitazone treatment in white and brown adipose tissue of mice with and without obesity due to high-fat diet or leptin deficiency. Thus, PPARgamma positively regulates ATGL mRNA and protein expression in mature adipocytes in vitro and in adipose tissue in vivo, suggesting a role for ATGL in mediating PPARgamma's effects on lipid metabolism. PMID- 17848641 TI - The cover. In the Magic Mirror. PMID- 17848642 TI - A piece of my mind. On knowledge. PMID- 17848643 TI - Interest surging in electroconvulsive and other brain stimulation therapies. PMID- 17848644 TI - MI risks linked to rosiglitazone. PMID- 17848645 TI - FDA: cold medications risky for young children. PMID- 17848646 TI - COPD and abdominal surgery. PMID- 17848647 TI - COPD and abdominal surgery. PMID- 17848648 TI - Diagnosis of erythema migrans. PMID- 17848649 TI - Patterns of prevalent major chronic disease among older adults in the United States. PMID- 17848650 TI - Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: a randomized controlled trial. AB - CONTEXT: High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown. OBJECTIVE: To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease. DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized controlled trial (2001-2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance < or =30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (> or = 15 micromol/L). INTERVENTION: Participants received a daily capsule containing 40 mg of folic acid, 100 mg of pyridoxine hydrochloride (vitamin B6), and 2 mg of cyanocobalamin (vitamin B12) or a placebo. MAIN OUTCOME MEASURES: The primary outcome was all cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of all or part of a lower extremity, a composite of these 3 plus all cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients. RESULTS: Mean baseline homocysteine level was 24.0 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < .001) in the vitamin group and 0.4 micromol/L (1.7%; P = .14) in the placebo group at 3 months, but there was no significant effect on mortality (448 vitamin group deaths vs 436 placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 MIs in the vitamin group vs 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60 amputations in the vitamin group vs 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P = .85), time to dialysis (P = .38), and time to thrombosis in hemodialysis patients (P = .97) did not differ between the vitamin and placebo groups. CONCLUSION: Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00032435. PMID- 17848651 TI - Carvedilol for children and adolescents with heart failure: a randomized controlled trial. AB - CONTEXT: Although beta-blockers improve symptoms and survival in adults with heart failure, little is known about these medications in children and adolescents. OBJECTIVE: To prospectively evaluate the effects of carvedilol in children and adolescents with symptomatic systemic ventricular systolic dysfunction. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, double blind, placebo-controlled study of 161 children and adolescents with symptomatic systolic heart failure from 26 US centers. In addition to treatment with conventional heart failure medications, patients were assigned to receive placebo or carvedilol. Enrollment began in June 2000 and the last dose was given in May 2005 (each patient received medication for 8 months). INTERVENTIONS: Patients were randomized in a 1:1:1 ratio to twice-daily dosing with placebo, low-dose carvedilol (0.2 mg/kg per dose if weight <62.5 kg or 12.5 mg per dose if weight > or =62.5 kg), or high-dose carvedilol (0.4 mg/kg per dose if weight <62.5 kg or 25 mg per dose if weight > or =62.5 kg) and were stratified according to whether each patient's systemic ventricle was a left ventricle or not. MAIN OUTCOME MEASURES: The primary outcome was a composite measure of heart failure outcomes in patients receiving carvedilol (low- and high-dose combined) vs placebo. Secondary efficacy variables included individual components of this composite, echocardiographic measures, and plasma b-type natriuretic peptide levels. RESULTS: There was no statistically significant difference between groups for the composite end point based on the percentage of patients who improved, worsened, or were unchanged. Among 54 patients assigned to placebo, 30 improved (56%), 16 worsened (30%), and 8 were unchanged (15%); among 103 patients assigned to carvedilol, 58 improved (56%), 25 worsened (24%), and 20 were unchanged (19%). The rates of worsening were lower than expected. The odds ratio for worsened outcome for patients in the combined carvedilol group vs the placebo group was 0.79 (95% CI, 0.36-1.59; P = .47). A prespecified subgroup analysis noted significant interaction between treatment and ventricular morphology (P = .02), indicating a possible differential effect of treatment between patients with a systemic left ventricle (beneficial trend) and those whose systemic ventricle was not a left ventricle (nonbeneficial trend). CONCLUSIONS: These preliminary results suggest that carvedilol does not significantly improve clinical heart failure outcomes in children and adolescents with symptomatic systolic heart failure. However, given the lower than expected event rates, the trial may have been underpowered. There may be a differential effect of carvedilol in children and adolescents based on ventricular morphology. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00052026. PMID- 17848652 TI - Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. AB - CONTEXT: Pioglitazone is widely used for glycemic control in patients with type 2 diabetes mellitus, but evidence is mixed regarding the influence of medications of this class on cardiovascular outcomes. OBJECTIVE: To systematically evaluate the effect of pioglitazone on ischemic cardiovascular events. DATA SOURCES AND STUDY SELECTION: A database containing individual patient-level time-to-event data collected during pioglitazone clinical trials was transferred from the drug's manufacturer for independent analysis. Trials were included if they were randomized, double-blinded, and controlled with placebo or active comparator. DATA EXTRACTION: The primary outcome was a composite of death, myocardial infarction, or stroke. Secondary outcome measures included the incidence of serious heart failure. A fixed-effects approach was used to combine the estimates across the duration strata and statistical heterogeneity across all the trials was tested with the I2 statistic. DATA SYNTHESIS: A total of 19 trials enrolling 16 390 patients were analyzed. Study drug treatment duration ranged from 4 months to 3.5 years. Death, myocardial infarction, or stroke occurred in 375 of 8554 patients (4.4%) receiving pioglitazone and 450 of 7836 patients (5.7%) receiving control therapy (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.72 0.94; P = .005). Progressive separation of time-to-event curves became apparent after approximately 1 year of therapy. Individual components of the primary end point were all reduced by a similar magnitude with pioglitazone treatment, with HRs ranging from 0.80 to 0.92. Serious heart failure was reported in 200 (2.3%) of the pioglitazone-treated patients and 139 (1.8%) of the control patients (HR, 1.41; 95% CI, 1.14-1.76; P = .002). The magnitude and direction of the favorable effect of pioglitazone on ischemic events and unfavorable effect on heart failure was homogeneous across trials of different durations, for different comparators, and for patients with or without established vascular disease. There was no evidence of heterogeneity across the trials for either end point (I2 = 0%; P = .87 for the composite end point and I2 = 0%; P = .97 for heart failure). CONCLUSIONS: Pioglitazone is associated with a significantly lower risk of death, myocardial infarction, or stroke among a diverse population of patients with diabetes. Serious heart failure is increased by pioglitazone, although without an associated increase in mortality. PMID- 17848653 TI - Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. AB - CONTEXT: Recent reports of serious adverse events with rosiglitazone use have raised questions about whether the evidence of harm justifies its use for treatment of type 2 diabetes. OBJECTIVE: To systematically review the long-term cardiovascular risks of rosiglitazone, including myocardial infarction, heart failure, and cardiovascular mortality. DATA SOURCES: We searched MEDLINE, the GlaxoSmithKline clinical trials register, the US Food and Drug Administration Web site, and product information sheets for randomized controlled trials, systematic reviews, and meta-analyses published in English through May 2007. STUDY SELECTION: Studies were selected for inclusion if they were randomized controlled trials of rosiglitazone for prevention or treatment of type 2 diabetes, had at least 12 months of follow-up, and monitored cardiovascular adverse events and provided numerical data on all adverse events. Four studies were included after detailed screening of 140 trials for cardiovascular events. DATA EXTRACTION: Relative risks (RRs) of myocardial infarction, heart failure, and cardiovascular mortality were estimated using a fixed-effects meta-analysis of 4 randomized controlled trials (n = 14 291, including 6421 receiving rosiglitazone and 7870 receiving control therapy, with a duration of follow-up of 1-4 years). RESULTS: Rosiglitazone significantly increased the risk of myocardial infarction (n = 94/6421 vs 83/7870; RR, 1.42; 95% confidence interval [CI], 1.06-1.91; P = .02) and heart failure (n = 102/6421 vs 62/7870; RR, 2.09; 95% CI, 1.52-2.88; P < .001) without a significant increase in risk of cardiovascular mortality (n = 59/6421 vs 72/7870; RR, 0.90; 95% CI, 0.63-1.26; P = .53). There was no evidence of substantial heterogeneity among the trials for these end points (I(2) = 0% for myocardial infarction, 18% for heart failure, and 0% for cardiovascular mortality). CONCLUSION: Among patients with impaired glucose tolerance or type 2 diabetes, rosiglitazone use for at least 12 months is associated with a significantly increased risk of myocardial infarction and heart failure, without a significantly increased risk of cardiovascular mortality. PMID- 17848654 TI - Management of intractable nausea and vomiting in patients at the end of life: "I was feeling nauseous all of the time . . . nothing was working". AB - Nausea and vomiting, symptoms that occur commonly near the end of life, represent a substantial source of physical and psychological distress for patients and families. In the context of the case of Mr Q, a 50-year-old man with metastatic esophageal cancer admitted to the hospital with intractable nausea and vomiting, we review the evaluation and treatment of this symptom complex. A thorough history and physical examination are essential first steps in the management of these patients because they define the severity of the symptoms and clues to their underlying etiology. Once the most likely cause is determined, the clinician discerns the mechanism, specific transmitters, and receptors by which this etiology is triggering nausea and vomiting. Subsequent pharmacological management focuses on prescribing the appropriate antagonist to the implicated receptors. If symptoms are refractory despite adequate dosage and around-the clock prophylactic administration, an empirical trial combining several therapies to block multiple emetic pathways should be attempted. Less traditional agents are also discussed, although evidence for their use is limited. Often, oral administration of medication is not feasible and alternate routes such as rectal suppositories, subcutaneous infusions, and orally dissolvable tablets should be considered. Using this step-wise approach, nausea and vomiting can be successfully managed in most patients at the end of life. PMID- 17848655 TI - Amyotrophic lateral sclerosis: "prepare for the worst and hope for the best" [corrected]. PMID- 17848656 TI - Limitations of applying summary results of clinical trials to individual patients: the need for risk stratification. PMID- 17848657 TI - B vitamins for the prevention of vascular disease: insufficient evidence to justify treatment. PMID- 17848658 TI - The importance of randomized controlled trials in pediatric cardiology. PMID- 17848659 TI - Cardiovascular risk and the thiazolidinediones: deja vu all over again? PMID- 17848660 TI - JAMA patient page. Chronic kidney disease. PMID- 17848661 TI - Experts fear Swedish snus sales in the U.S. could thwart anti-tobacco measures. PMID- 17848662 TI - Gene mutation revelation points to new target for myeloma treatment, studies say. PMID- 17848663 TI - Cancer killer may be "silent" no more. PMID- 17848664 TI - Soy and prostate cancer study results mixed. PMID- 17848665 TI - Untangling differences in cancer mortality rates: a closer look at race and education. PMID- 17848666 TI - High-grade prostate cancer in the Prostate Cancer Prevention Trial: fact or artifact? PMID- 17848667 TI - Stat bite: Female Ph.D. graduates by field. PMID- 17848668 TI - Detection bias due to the effect of finasteride on prostate volume: a modeling approach for analysis of the Prostate Cancer Prevention Trial. AB - BACKGROUND: The Prostate Cancer Prevention Trial (PCPT) demonstrated a 24.8% reduction in the 7-year prevalence of prostate cancer among patients treated with finasteride (5 mg daily) compared with that among patients treated with placebo; however, a 25.5% increase in the prevalence of high-Gleason grade tumors was observed, the clinical significance of which is unknown. One hypothesized explanation for this increase is that finasteride reduced prostate volume, leading to detection of more high-grade tumors due to increased sampling density. This possibility was investigated in an observational reanalysis of the PCPT data, with adjustment for sampling density. METHODS: A logistic model for the association of high-grade (Gleason score 7-10) prostate cancer with baseline covariates and/or baseline covariates plus prostate volume and number of cores obtained at biopsy was developed using the placebo group (n = 4775) of the PCPT. This model was then applied to the finasteride group (n = 5123) to compare the predicted and observed numbers of high-grade tumors in that group. In a second approach, odds ratios (ORs) for prostate cancer in the finasteride versus placebo groups calculated from binary and polytomous logistic regression models that contained or excluded covariates for gland volume and number of needle cores were compared. RESULTS: Median prostate volume was 25% lower in the finasteride group (median = 25.1 cm3) than in the placebo group (median = 33.5 cm3). The logistic model developed in the placebo group showed that the likelihood of detection of high-grade prostate cancer decreased as volume increased (for each 10 cm3 increase in prostate volume, OR = 0.81, 95% confidence interval [CI] = 0.74 to 0.90). Based on this model, 239 high-grade prostate cancers were predicted in the finasteride group, whereas 243 were observed, a non-statistically significant difference. Among all participants, the odds ratios for high-grade cancer in the finasteride versus placebo groups decreased from 1.27 (95% CI = 1.05 to 1.54) with adjustment for baseline covariates to 1.03 (95% CI = 0.84 to 1.26) following additional adjustment for gland volume and number of biopsy cores in binary outcome models and from 1.14 (95% CI = 0.94 to 1.38) to 0.88 (95% CI = 0.72 to 1.09) following these adjustments in the polytomous models. CONCLUSIONS: Although analyses using postrandomization data require cautious interpretation, these results suggest that sampling density bias alone could explain the excess of high grade cancers among the finasteride-assigned participants in the PCPT. PMID- 17848669 TI - Lung cancer survival and functional polymorphisms in MBL2, an innate-immunity gene. AB - BACKGROUND: The relationship among chronic inflammation, innate immunity, and cancer is well established. Mannose-binding lectin (MBL) is a key player in innate immunity. Five polymorphisms in the promoter and first exon of the MBL2 gene alter the expression and function of MBL in humans and are associated with inflammation-related disease susceptibility. These five polymorphisms create six well-characterized haplotypes that result in lower (i.e., LYB, LYC, HYD, and LXA) or higher (i.e., HYA and LYA) serum MBL concentrations. We investigated whether survival of patients with lung cancer was associated with these polymorphisms. METHODS: We used a multivariable Cox proportional hazards model to study the association between MBL2 polymorphisms and their haplotypes and diplotypes in 558 white and 173 African American patients with non-small-cell lung cancer in the Baltimore, MD, area and lung cancer mortality. Smoking history and race were obtained from interviews, tumor stage was obtained from medical records, and cause of death was obtained from the National Death Index. All statistical tests were two-sided. RESULTS: We found a statistically significant association between the X allele of the promoter Y/X polymorphism (which results in a lower serum MBL concentration) and improved lung cancer survival among white patients (risk ratio [RR] of death from lung cancer with X/X or X/Y genotype compared with Y/Y genotype = 0.61, 95% confidence interval [CI] = 0.46 to 0.81) but not among African American patients (RR = 1.11, 95% CI = 0.69 to 1.77). The associations among white patients were strongest in heavy smokers and were independent of stage. We also found a statistically significant interaction between the Y/X polymorphism and race for lung cancer survival (P(interaction) = .019). The MBL2 LXA haplotype and XA/B diplotype, which are also associated with low serum MBL levels, were statistically significantly associated with improved lung cancer survival among white patients. CONCLUSION: The functional Y/X polymorphism of the innate-immunity gene MBL2 and MBL2 haplotypes and diplotypes appear to be associated with lung cancer survival among white patients. PMID- 17848670 TI - Cancer mortality in the United States by education level and race. AB - BACKGROUND: Although both race and socioeconomic status are well known to influence mortality patterns in the United States, few studies have examined the simultaneous influence of these factors on cancer incidence and mortality. We examined relationships among race, education level, and mortality from cancers of the lung, breast, prostate, colon and rectum, and all sites combined in contemporary US vital statistics. METHODS: Age-adjusted cancer death rates (with 95% confidence intervals [CIs]) were calculated for 137,708 deaths among 119,376,196 individuals aged 25-64 years, using race and education information from death certificates and population denominator data from the US Bureau of the Census, for 47 states and Washington, DC, in 2001. Relative risk (RR) estimates were used to compare cancer death rates in persons with 12 or fewer years of education with those in persons with more than 12 years of education. RESULTS: Educational attainment was strongly and inversely associated with mortality from all cancers combined in black and white men and in white women. The all-cancer death rates were nearly identical for black men and white men with 0-8 years of education (224.2 and 223.6 per 100,000, respectively). The estimated relative risk for all-cancer mortality comparing the three lowest (< or = 12 years) with the three highest (> 12 years) education categories was 2.38 (95% CI = 2.33 to 2.43) for black men, 2.24 (95% CI = 2.23 to 2.26) for white men, 1.43 (95% CI = 1.41 to 1.46) for black women, and 1.76 (95% CI = 1.75 to 1.78) for white women. For both men and women, the magnitude of the relative risks comparing the three lowest educational levels with the three highest within each race for all cancers combined and for lung and colorectal cancers was higher than the magnitude of the relative risks associated with race within each level of education, whereas for breast and prostate cancer the magnitude of the relative risks associated with race was higher than the magnitude of the relative risks associated with level of education within each racial group. Among the most important and novel findings were that black men who completed 12 or fewer years of education had a prostate cancer death rate that was more than double that of black men with more schooling (10.5 versus 4.8 per 100,000 men; RR = 2.17, 95% CI = 1.82 to 2.58) and that, in contrast with studies of mortality rates in earlier time periods, breast cancer mortality rates were higher among women with less education than among women with more education (37.0 and 31.1 per 100,000, respectively, for black women and 25.2 versus 18.6 per 100,000, respectively, for white women). CONCLUSION: Cancer death rates vary considerably by level of education. Identifying groups at high risk of death from cancer by level of education as well as by race may be useful in targeting interventions and tracking cancer disparities. PMID- 17848671 TI - Detection of prostate cancer via biopsy in the Medicare-SEER population during the PSA era. AB - BACKGROUND: Despite the considerable attention given to the prostate-specific antigen (PSA) as a screening test for prostate cancer, it is needle biopsy--and not the PSA test result--that actually establishes the diagnosis of prostate cancer. We sought national estimates on the proportion of men found to have prostate cancer after a needle biopsy of the prostate and the risk of subsequent biopsies among those not found to have prostate cancer. METHODS: We linked Medicare claims data to Surveillance, Epidemiology, and End Results (SEER) data to analyze outcomes after 10,429 needle biopsies performed in 1993 through 2001 in 8273 men aged 65 years and older enrolled in Medicare Part B who resided in a SEER area. We determined the proportion of needle biopsies that were followed by a diagnosis of prostate cancer, the cumulative risk of prostate cancer following multiple biopsies, and the risk of subsequent biopsy among men not found to have prostate cancer in the previous biopsy. All statistical tests were two-sided. RESULTS: The overall proportion of needle biopsies found to contain prostate cancer was 32% (95% confidence interval [CI] = 31% to 33%). The yield increased with age (26% for men aged 65-69 years, 31% for men aged 70-74 years, 35% for men aged 75-79 years, and 41% for men aged 80 years and older; P(trend)<.001). The cumulative risk of prostate cancer diagnosis increased with repeated biopsy, with 50% of men receiving a prostate cancer diagnosis after two biopsies, 62% after three biopsies, and 68% after four biopsies. Among men whose first recorded biopsy did not detect prostate cancer, the risk of having a subsequent biopsy was 11.6% (95% CI = 11% to 12%) at 1 year and 38% (95% CI = 36% to 40%) at 5 years. CONCLUSIONS: About one-third of prostate biopsies identified prostate cancer in this population. Men not found to have prostate cancer on a first biopsy frequently undergo repeat biopsies, which raise the cumulative risk of prostate cancer diagnosis. PMID- 17848672 TI - A woman and her canary: a tale of chlamydiae and lymphomas. PMID- 17848673 TI - Finasteride and high-grade prostate cancer in the Prostate Cancer Prevention Trial. AB - BACKGROUND: The Prostate Cancer Prevention Trial (PCPT) reported a decreased incidence of prostate cancer overall but an increase in the incidence of high grade prostate cancer with finasteride compared with placebo. We assessed whether the increased high-grade prostate cancer associated with finasteride in the PCPT was due to finasteride's potential effects on tumor morphology or prostate size. METHODS: Prostate biopsies with Gleason score 8-10 (n = 90, finasteride; n = 52, placebo) were examined histologically for hormonal effects, and those with Gleason score 7-10 (n = 282, finasteride; n = 244, placebo) were examined for pathologic surrogates of disease extent. Prostate volumes were measured at biopsy. Samples from radical prostatectomies (n = 222, finasteride; n = 306, placebo) were examined for tumor grade and extent, and, where possible, grades at biopsy and prostatectomy were compared between the groups. Logistic regression was used to analyze differences between treatment groups with respect to pathologic criteria. All statistical tests were two-sided. RESULTS: Degenerative hormonal changes in high-grade biopsies were equivalent between the finasteride and placebo groups, but prostate volumes were lower in the finasteride group (median = 25.1 versus 34.4 cm3, P<.001). Pathologic surrogates for tumor extent were lower with finasteride than with placebo, including mean percentage of positive cores (34% versus 38%, P = .016), mean tumor linear extent (greatest [4.4 versus 4.8 mm, P = .19] and aggregate [7.6 versus 9.2 mm, P = .13]), bilaterality (22.8% versus 30.6%, P = .046), and perineural invasion (14.2% versus 20.3%, P = .07). Among patients who had prostatectomy, the finasteride associated increase in high-grade disease (Gleason score > or = 7) at biopsy (42.7% finasteride versus 25.4% placebo, P<.001) was diminished at prostatectomy (46.4% finasteride versus 38.6% placebo, P = .10). Biopsy identified a greater proportion of patients with high-grade disease present at prostatectomy in the finasteride group than in the placebo group (69.7% versus 50.5%, P = .01). The rate of upgrading (from low-grade cancer at biopsy to high-grade cancer at prostatectomy) and pathologic stage at prostatectomy were similar in both groups. CONCLUSIONS: Effects of finasteride on prostate volume and selective inhibition of low-grade cancer, rather than effects on tumor morphology, may have contributed to the increase in high-grade cancers with finasteride in the PCPT. Although induction of high-grade cancer cannot be excluded, the results suggest that high-grade cancer was detected earlier and was less extensive in the finasteride group than in the placebo group. PMID- 17848674 TI - Re: Atopy and risk of non-Hodgkin lymphoma. PMID- 17848675 TI - Re: Polychemotherapy for early breast cancer: results from the international adjuvant breast cancer chemotherapy randomized Trial. PMID- 17848676 TI - Financial conflicts of interest among ASCO annual meeting abstract authors, speakers, and planners. PMID- 17848677 TI - Examination of the therapeutic potential of Delta-24-RGD in brain tumor stem cells: role of autophagic cell death. AB - The eradication of brain tumor stem cells is essential for long-term brain tumor remission after treatment. In this study, we examined the therapeutic potential of an oncolytic adenovirus, Delta-24-RGD, targeted to the abnormal p16INK4/Rb pathway in brain tumor stem cells. Four brain tumor stem cell lines from surgical glioblastoma specimens expressed high levels of adenoviral receptors and allowed for efficient viral infection, replication, and oncolysis in an Rb-dependent manner. Delta-24-RGD induced autophagic cell death, as indicated by accumulation of Atg5 and LC3-II protein and autophagic vacuoles. Treatment of xenografts derived from brain tumor stem cells with Delta-24-RGD statistically significantly improved the survival of glioma-bearing mice (means: 38.5 versus 66.3 days, difference = 27.8 days, 95% confidence interval = 19.5 to 35.9 days, P <.001). Analyses of treated tumors showed that Atg5 expression colocalized with viral fiber protein and delineated a wave front of autophagic cells that circumscribed areas of virally induced necrosis. Our results show for the first time that brain tumor stem cells are susceptible to adenovirus-mediated cell death via autophagy in vitro and in vivo. PMID- 17848678 TI - Malignant intraductal papillary mucinous neoplasm of the pancreas: in situ versus invasive carcinoma surgical resectability. AB - PURPOSE: To retrospectively evaluate computed tomographic (CT) findings in patients with in situ and invasive malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas and to evaluate the accuracy for surgical resectability, with surgery and pathologic analysis as the reference standards. MATERIALS AND METHODS: Institutional review board approval was obtained, and the informed consent requirement was waived. Forty-six patients with malignant IPMN proved at pathologic examination of the surgically resected specimen (n = 44) or laparotomy (n = 2) underwent surgery after multidetector CT was performed. CT findings were retrospectively evaluated to determine if a pancreatic malignant IPMN tumor was present; to make this determination, CT criteria were used to differentiate in situ from invasive tumors and signs of unresectability (liver metastasis, vascular CT pattern of encasement, or regional lymph node metastasis). The extent of the vascular CT pattern of encasement was recorded for each patient (no obliteration of the fat plane, obliteration of the fat plane of <50%, or obliteration of the fat plane of > or =50%). Statistical analysis was performed with the chi(2) and Student t tests. RESULTS: CT revealed a mural nodule in the pancreatic duct wall in 14 patients with in situ carcinoma and one patient with invasive carcinoma (P < .003). CT revealed an infiltrative pancreatic mass in 17 patients with invasive carcinoma and two patients with in situ carcinoma (P < .02). Of the mural nodules, 93% were seen in patients with in situ carcinoma, whereas 90% of infiltrative pancreatic masses were observed in patients with invasive carcinomas. The positive predictive value of CT for determining resectability was 100%, and the overall accuracy of CT for determining resectability and unresectability was 74%. The positive predictive value of CT for determining unresectability was 17%, mainly owing to overestimation of arterial invasion. CONCLUSION: CT is helpful in the differentiation of in situ and invasive IPMN. Classic vascular invasion criteria lead to the overestimation of surgical tumor unresectability in patients with malignant IPMN. PMID- 17848679 TI - Lower extremity arterial disease: multidetector CT angiography meta-analysis. AB - PURPOSE: To obtain the best available estimates of the diagnostic performance of multidetector computed tomographic (CT) angiography compared with that of digital subtraction angiography (DSA) in the assessment of symptomatic lower extremity arterial disease and to identify the most important sources of variation in diagnostic performance between studies. MATERIALS AND METHODS: Reports of studies published from January 2000 through April 2006 in English, German, French, or Spanish were searched for by using the MEDLINE, EMBASE, and Cochrane databases. Studies were included if they allowed construction of 2 x 2 contingency tables for the detection of stenosis of 50% or greater at multidetector CT angiography compared with that at DSA -- the reference standard -- in patients with claudication or critical ischemia. Two observers extracted data about study design, patient characteristics, arterial tracts, and technical protocols. Random effects summary receiver operating characteristic analysis was performed to examine the influence of these data on diagnostic performance. RESULTS: Of the 70 studies initially identified, 12 were included in which multidetector CT angiography was used to evaluate 9541 arterial segments in 436 patients. The pooled sensitivity and specificity for detecting a stenosis of at least 50% per segment were 92% (95% confidence interval: 89%, 95%) and 93% (95% confidence interval: 91%, 95%), respectively. Three studies provided data about the diagnostic performance of multidetector CT angiography in subdivisions of the arterial tract. The diagnostic performance of multidetector CT angiography in the infrapopliteal tract was lower than but not significantly different from that in the aortoiliac (P > .11) and femoropopliteal (P > .40) tracts. Regression analysis showed that diagnostic performance was not significantly influenced by differences in study characteristics. CONCLUSION: Multidetector CT angiography is an accurate diagnostic test in the assessment of arterial disease (> or =50% stenosis) of the entire lower extremity. PMID- 17848680 TI - R2 and R2* mapping for sensing cell-bound superparamagnetic nanoparticles: in vitro and murine in vivo testing. AB - PURPOSE: To prospectively determine the cellular iron uptake by using R2 and R2* mapping with multiecho readout gradient-echo and spin-echo sequences. MATERIALS AND METHODS: All experiments were approved by the institutional animal care committee. Lung carcinoma cells were lipofected with superparamagnetic iron oxides (SPIOs). Agarose gel phantoms containing (a) 1 x 10(5) CCL-185 cells per milliliter of agarose gel with increasing SPIO load (0.01-5.00 mg of iron per milliliter in the medium), (b) different amounts (5.0 x 10(3) to 2.5 x 10(5) cells per milliliter of agarose gel) of identically loaded cells, and (c) free (non-cell-bound) SPIOs at the iron concentrations described for (b) were analyzed with 3.0-T R2 and R2* relaxometry. Iron uptake was analyzed with light microscopy, quantified with atomic emission spectroscopy (AES), and compared with MR data. For in vivo relaxometry, agarose gel pellets containing SPIO-labeled cells, free SPIO, unlabeled control cells, and pure agarose gel were injected into three nude mice each. Linear and nonlinear regression analyses were performed. RESULTS: Light microscopy and AES revealed efficient SPIO particle uptake (mean uptake: 0.22 pg of iron per cell +/- 0.1 [standard deviation] for unlabeled cells, 31.17 pg of iron per cell +/- 4.63 for cells incubated with 0.5 mg/mL iron). R2 and R2* values were linearly correlated with cellular iron load, number of iron-loaded cells, and content of freely dissolved iron (r(2) range, 0.92-0.99; P < .001). For cell-bound SPIO, R2* effects were significantly greater than R2 effects (P < .01); for free SPIO, R2 and R2* effects were similar. In vivo relaxometry enabled accurate prediction of the number of labeled cells. R2' (R2* - R2) mapping enabled differentiation between cell-bound and free iron in vitro and in vivo. CONCLUSION: Quantitative R2 and R2* mapping enables noninvasive estimations of cellular iron load and number of iron-labeled cells. Cell-bound SPIOs can be differentiated from free SPIOs with R2' imaging. PMID- 17848681 TI - Three-dimensional proton MR spectroscopy of human prostate at 3 T without endorectal coil: feasibility. AB - PURPOSE: To evaluate sensitivity and specificity of proton magnetic resonance (MR) spectroscopy of the prostate with external surface coil elements at 3 T for differentiation of cancer from healthy tissue within an acceptable measurement time, by using histopathologic findings as the reference standard. MATERIALS AND METHODS: The study was approved by the institutional review board; informed consent was obtained. Forty-five men (age range, 51-70 years) underwent 3-T MR imaging with external radiofrequency surface coils for signal reception. MR spectroscopy was performed with acquisition-weighted three-dimensional water- and lipid-suppressed point-resolved spectroscopy pulse sequence. Voxels were classified into healthy peripheral zone, central gland, and periurethral zone and cancer tissue. Cancer voxels were classified according to cancer size and certainty in matching histopathologic findings with MR images. After visual inspection of automated fitting of classified voxels, the choline plus creatine to-citrate (Cho + Cr/Cit) ratio was calculated for all tissues. Area under the receiver operating characteristic curves (A(z)) values were used to assess accuracy of discrimination of cancer from healthy tissues. P < .05 indicated a significant difference. RESULTS: After exclusion of four patients with no voxels that passed visual inspection of the automated fit, a median of 82% of the classified voxels per patient was used in the analysis. Mean Cho + Cr/Cit ratios for healthy tissues were 0.22 +/- 0.12 (standard deviation) for peripheral zone, 0.34 +/- 0.14 for central gland, and 0.36 +/- 0.20 for periurethral area; all were significantly different from that of cancer (P < .001). A(z) for discrimination of probable and definite cancer tissue from healthy tissue for the peripheral zone (0.84) was significantly higher than that for the central gland (0.69) (P < .05). CONCLUSION: Three-dimensional proton MR spectroscopy of the prostate, with a combination of only external radiofrequency surface coils at 3 T, can be used to discriminate cancer from healthy tissue. PMID- 17848682 TI - Changes in cerebral perfusion after revascularization of symptomatic carotid artery stenosis: CT measurement. AB - PURPOSE: To prospectively evaluate changes in brain perfusion computed tomographic (CT) parameters after revascularization of unilateral symptomatic carotid artery stenosis and to determine whether pretreatment perfusion CT parameters can be used to predict changes in cerebral hemodynamics after treatment. MATERIALS AND METHODS: This study was medical ethics committee approved, and written informed consent was obtained from all patients. Thirty-six patients (23 men, 13 women; mean age, 67 years) with unilateral symptomatic carotid artery stenosis underwent multi-detector row perfusion CT before and after revascularization. Mean transit time (MTT), cerebral blood volume (CBV), and cerebral blood flow (CBF) were calculated, and relative values based on the comparison between symptomatic and asymptomatic hemispheres-specifically, relative CBV, relative CBF, and difference in MTT-were derived. The absolute and relative perfusion values before treatment were assessed and compared with posttreatment values. These analyses were performed for the group as a whole by using the t test and after subdividing patients into three tertiles according to the difference in MTT by using the Wilcoxon signed rank test. RESULTS: Among the absolute perfusion values, only the MTT in the symptomatic hemisphere improved significantly after treatment (P < .01). All relative values (difference in MTT, relative CBV, and relative CBF) changed significantly after treatment (P < .05). When the patients were subdivided into three tertiles according to difference in MTT, no significant change in any relative perfusion value could be demonstrated in the lowest tertile, only the difference in MTT improved significantly (P = .004) in the middle tertile, and all relative perfusion values changed significantly (P = .002) in the highest tertile. CONCLUSION: Compared with relative CT perfusion values based on interhemispheric comparison, absolute perfusion CT values are less suited for demonstrating changes in cerebral perfusion after revascularization in patients with unilateral symptomatic carotid artery stenosis. PMID- 17848683 TI - Coronary artery motion and cardiac phases: dependency on heart rate -- implications for CT image reconstruction. AB - This study had institutional review board approval; written informed consent was obtained. The purpose was to prospectively determine the heart rate (HR) dependency of three-dimensional (3D) coronary artery motion by incorporating into analysis the durations of systole and diastole. Thirty patients (seven women, 23 men; mean age, 56.6 years +/- 12.7 [standard deviation]; HR: 45-100 beats per minute) underwent electrocardiographically gated 64-section computed tomographic (CT) coronary angiography to determine coronary motion velocities at bifurcation points. Significance of velocity differences (P < .05) was determined by using analysis of variance for repeated measures and Bonferroni post hoc tests. HR dependency was determined by using linear regression analysis. HR significantly affected 3D coronary motion (r = 0.47, P < .009) through nonproportional shortening of systole and diastole (r = -0.82, P < .001), leading to percentage reconstruction interval shifts of coronary velocity troughs and peaks (P < .01). Results suggest that image reconstruction algorithms at CT coronary angiography be adapted to the individual patient's HR. PMID- 17848684 TI - A true screening environment for review of interval breast cancers: pilot study to reduce bias. AB - PURPOSE: To retrospectively assess the feasibility of an uninformed review process to evaluate interval breast cancers and to compare the number of false negative cancers detected at uninformed review with the number detected at standard informed review. MATERIALS AND METHODS: Institutional review board approval was obtained for this retrospective study, and informed consent was waived. Mammograms showing interval cancer were included in the daily work of radiologists in a high-volume screening center. Each of three experienced radiologists read studies in the normal screening environment, without knowledge that identifiers had been changed to conceal the fact that studies were not current (ie, uninformed review). Results were compared with the standard review procedure, in which mammograms showing interval cancers were mixed with normal mammograms and read in a panel of 17-20 interval cancers per 80 normal studies by radiologists who were aware that they were participating in a review process (ie, informed review). RESULTS: Of 21 interval cancers, six (29%) were interpreted as positive more often by the informed radiologists than by the uninformed radiologists. For 14 (67%) cancers, there was no difference in detection rate between the two groups, and one cancer (5%) was seen by one of the uninformed radiologists but by none of the informed radiologists. The screening environment review process was found to be feasible at the low volumes tested. CONCLUSION: The number of false-negative cancers was higher in the informed review than in the uninformed review. This result suggests that bias exists with the informed review process. PMID- 17848685 TI - Management of suspected acute pulmonary embolism in the era of CT angiography: a statement from the Fleischner Society. PMID- 17848686 TI - The Aryl hydrocarbon receptor: an illuminating effector of the UVB response. AB - The aryl hydrocarbon receptor (AhR) is a cytosolic ligand-activated transcription factor that mediates most of the toxic and carcinogenic effects of drugs and environmental toxins collectively known as xenobiotics. Ligand activation of the AhR stimulates the transcription of genes that encode several xenobiotic metabolizing enzymes. The molecular mechanisms and signaling pathways evoked by the activation of the AhR are becoming increasingly understood and underscore the participation of the AhR in crucial processes, including cellular stress response, proliferation, differentiation, inflammation, and carcinogenesis. Studies now implicate the AhR as an integral part of the multifaceted signal transduction pathway initiated by the exposure of keratinocytes to ultraviolet B radiation (UVB), which is the most ubiquitous hazard to human skin and the principal risk factor for skin cancer. Ligand-dependent activation of the AhR in the cytosol provides a molecular bridge that links cytoplasmic events to nuclear signals, thus unmasking a previously unknown role for this transcription factor in the complex cellular response to UVB. PMID- 17848687 TI - Hedgehog signaling: cooking with Gas1. AB - The mechanisms by which morphogens, such as Sonic hedgehog (Shh), specify distinct cell fates in a concentration-dependent manner are not fully understood. Shh signaling is regulated by a feedback network that comprises Shh-binding factors, the expression of which is controlled by the Hedgehog pathway itself. Recent studies have identified the hedgehog-binding protein growth arrest specific gene 1 (Gas1) as a component of this network. Gas1 binds Shh to promote signaling, but its expression is subsequently inhibited by pathway activity. Gas1(-/-) mice display Shh dosage-dependent phenotypes in the neural tube, midface, and digits. Ectopic expression and in vitro assays indicate that Gas1 binds Shh synergistically with the Hedgehog receptor Patched1 and promotes signaling in a cell-autonomous fashion. Furthermore, Gas1 cooperates with another component of the feedback network, Cdo, in patterning the neural tube and midface. The coordinate regulation of the activity and expression of several different positively and negatively acting Shh binding proteins should result in fine-tuned modulation of graded Shh signaling. PMID- 17848688 TI - US MR imaging correlation in pathologic conditions of the scrotum. AB - Ultrasonography (US) is usually the initial imaging modality for evaluation of pathologic conditions of the scrotum. However, magnetic resonance (MR) imaging can be useful as a problem-solving tool when sonographic findings are equivocal. MR imaging allows characterization of scrotal masses as intratesticular or extratesticular and can demonstrate various types of lesions and tissue, including cysts or fluid, solid masses, fat, and fibrosis. MR imaging may be of value when the location of a scrotal mass is uncertain or when US does not allow differentiation between a solid mass and an inflammatory or vascular abnormality. Gadolinium-enhanced MR imaging can help differentiate between a benign cystic lesion and a cystic neoplasm. Gadolinium-enhanced imaging can also be used to demonstrate areas of absent or reduced testicular perfusion, such as in segmental testicular infarct. Finally, MR imaging can demonstrate an intraabdominal undescended testis, which can be difficult to detect with US, and is superior to US in differentiation between an undescended testis and testicular agenesis. PMID- 17848689 TI - Tuberculosis: a radiologic review. AB - Tuberculosis has shown a resurgence in nonendemic populations in recent years, a phenomenon that has been attributed to factors such as increased migration and the human immunodeficiency virus epidemic. Although the thorax is most frequently involved, tuberculosis may involve any of a number of organ systems (eg, the respiratory, cardiac, central nervous, musculoskeletal, gastrointestinal, and genitourinary systems), and timely diagnosis of the disease is paramount, since delayed treatment is associated with severe morbidity. Unfortunately, a history of infection with or exposure to tuberculosis may or may not be present, and evidence of active tuberculosis is present in less than 50% of cases. A negative tuberculin skin test does not in itself exclude infection. Furthermore, the clinical and radiologic features of tuberculosis may mimic those of many other diseases. Therefore, although in many cases biopsy or culture specimens are required to make the definitive diagnosis, it is imperative that radiologists and clinicians understand the typical distribution, patterns, and imaging manifestations of tuberculosis. PMID- 17848690 TI - Adding local flavor to world class imaging. AB - Chicago, the host city for the annual meeting of the RSNA (Radiological Society of North America), is the quintessential place to obtain certain foods, among them deep dish pizza, the Italian beef sandwich, and the Chicago-style hot dog. Given some appropriate nutritional concerns about these items, it is important to realize that healthier alternatives are grown, produced, and sold regionally. Chicago has also for years been known as one of America's great restaurant towns. However, the French delicacy foie gras cannot be found on the menu of any of its five-star establishments, as the sale of this dish became illegal in 2006. Diagnostic imaging offers a unique perspective on the local Chicago cuisine. PMID- 17848691 TI - Imaging features of invasive and noninvasive fungal sinusitis: a review. AB - Fungal sinusitis was once considered a rare disorder but is now reported with increasing frequency throughout the world. The classification of fungal sinusitis has evolved in the past two decades, and this entity is now thought to comprise five subtypes. Acute invasive fungal sinusitis, chronic invasive fungal sinusitis, and chronic granulomatous invasive fungal sinusitis make up the invasive group, whereas noninvasive fungal sinusitis is composed of allergic fungal sinusitis and fungus ball (fungal mycetoma). These five subtypes are distinct entities with different clinical and radiologic features. The treatment strategies for the subtypes are also different, as are their prognoses. An understanding of the different types of fungal sinusitis and knowledge of their particular radiologic features allow the radiologist to play a crucial role in alerting the clinician to use appropriate diagnostic techniques for confirmation. Prompt diagnosis and initiation of appropriate therapy are essential to avoid a protracted or fatal outcome. PMID- 17848692 TI - Cardiac CT of the transplanted heart: indications, technique, appearance, and complications. AB - Effective antirejection therapy and infection control have significantly improved the long-term survival of heart transplant recipients, but coronary allograft vasculopathy remains an important limiting factor. Most heart transplant recipients undergo annual coronary angiography for the detection of allograft vasculopathy, which is often clinically silent. Angiography allows detection of vasculopathy only indirectly, with depiction of the lumen, and does not depict the wall thickening and intimal hyperplasia that typify this disease; the procedure also is invasive and is associated with a 1%-2% risk of complication. In contrast, electrocardiographically gated multidetector computed tomography (CT) can provide a comprehensive and noninvasive evaluation of the transplanted heart in a single study. Cardiac CT enables evaluation of the coronary artery lumen and wall and thus may be used for screening, diagnosis, grading, and follow up of coronary allograft vasculopathy. It also may be used to detect other posttransplantation complications, such as malignancy and infection, and to assess cardiac and vascular anastomoses and cardiac function. However, special strategies may be needed to reduce the transplant heart rate so as to obtain images of diagnostic quality. PMID- 17848693 TI - Three-dimensional contrast-enhanced MR angiography of aortic dissection: a pictorial essay. AB - Aortic dissection is a catastrophic aortic disorder with high morbidity and mortality rates. Prognosis and treatment vary with different types of aortic dissection; therefore, prompt and accurate diagnosis is essential. Ultrasonography is widely available and can be used even in relatively unstable patients. However, it has limited diagnostic accuracy and cannot provide three dimensional (3D) display images for treatment planning. Both computed tomographic (CT) angiography and 3D contrast material-enhanced magnetic resonance (MR) angiography can accurately demonstrate aortic dissection, with CT having the advantages of wider availability and shorter imaging times. However, contrast enhanced MR angiography is more suitable in medically stable patients, does not involve nephrotoxic contrast agent or ionizing radiation, and offers greater ease and speed of postprocessing. In clinical practice, contrast-enhanced MR angiography can provide high-quality imaging data suitable for 3D reconstructions. It also has excellent spatial and contrast resolution and allows studies to be performed in multiple vascular phases, making it valuable for the diagnosis and classification of aortic dissection and in providing information that is helpful for treatment planning. Three-dimensional contrast-enhanced MR angiography with postprocessing is a fast, accurate, and noninvasive technique that may prove to be the optimal imaging modality in medically stable patients with aortic dissection. PMID- 17848694 TI - Classic imaging signs of congenital cardiovascular abnormalities. AB - Cardiovascular imaging is a rapidly evolving field that requires familiarity with the appearances of pediatric and adult cardiovascular diseases on chest radiographs as well as images obtained with computed tomography, magnetic resonance imaging, and angiography. To accurately identify congenital abnormalities affecting the heart and vessels of the thorax, radiologists must recognize the imaging features and understand their pathophysiologic origin. The cardiovascular imaging signs of congenital anomalies that are most often seen in radiologic practice include the egg on a string (seen in transposition of the great arteries), snowman (total anomalous pulmonary venous return), scimitar (partial anomalous pulmonary venous return), gooseneck (endocardial cushion defect), figure of three and reverse figure of three (aortic coarctation), boot shaped heart (tetralogy of Fallot), and box-shaped heart (Ebstein anomaly). PMID- 17848695 TI - Multimodality imaging of Hodgkin disease and non-Hodgkin lymphomas in children. AB - Lymphomas account for 10%-15% of all childhood cancers and include a number of different pathologic subtypes, which arise from the constituent cells of the immune system or from their precursors. All organ systems may be involved at some stage of the disease, including the central nervous system, head and neck, thorax, abdomen, gonads, and bone. However, at onset, nodal and splenic involvement are more common in Hodgkin disease, whereas extranodal involvement is more frequent in non-Hodgkin lymphomas. Diagnostic imaging modalities have a fundamental role in the staging of lymphomas and, owing to major advances during the past two decades, make surgical staging unnecessary in most cases. Conventional, sonographic, and cross-sectional imaging techniques are excellent tools for evaluating the extent and sites of disease in childhood lymphomas. Familiarity with the spectrum of imaging findings in lymphomas is essential for radiologists to enable them to provide guidance for the treating physicians. PMID- 17848696 TI - Scintigraphic imaging of body neuroendocrine tumors. AB - Radionuclide imaging is often used in the diagnosis and work-up of a wide range of neoplasms, on the basis of the biologic behavior of the tumor. Neuroendocrine tumors are a subgroup of neoplasms that are generally small and slow growing, and consequently their identification with conventional anatomic imaging can be difficult. Depending on the physiologic properties of the tumor, functional images obtained with radionuclides are often complementary to anatomic images, not only in the localization of the tumor and its metastases, but also in the assessment of prognosis and response to therapy. Familiarity with the choice of the appropriate radiopharmaceutical, proper imaging protocols, and the wide range of imaging patterns will enable the radiologist to guide the clinician in case management. PMID- 17848697 TI - Primary gastrointestinal lymphoma: spectrum of imaging findings with pathologic correlation. AB - Gastrointestinal lymphoma is an uncommon disease but is the most frequently occurring extranodal lymphoma and is almost exclusively of non-Hodgkin type. Primary gastrointestinal lymphoma most commonly involves the stomach but can involve any part of the gastrointestinal tract from the esophagus to the rectum. Risk factors for the development of gastrointestinal lymphoma include Helicobacter pylori infection, immunosuppression after solid organ transplantation, celiac disease, inflammatory bowel disease, and human immunodeficiency virus infection. Although gastrointestinal lymphoma has a wide variety of imaging appearances and definitive diagnosis relies on histopathologic analysis, certain findings (eg, a bulky mass or diffuse infiltration with preservation of fat planes and no obstruction, multiple site involvement, associated bulky lymphadenopathy) can strongly suggest the diagnosis. Imaging also plays an important role in the detection of complications such as perforation, obstruction, and fistulization. The most commonly used imaging modalities are barium examination and computed tomography (CT). These modalities are complementary, although CT provides a better overall assessment of the disease stage. PMID- 17848698 TI - Disconnection of the pancreatic duct: an important but overlooked complication of severe acute pancreatitis. AB - In patients with severe acute pancreatitis, the percentage of necrosis of pancreatic glandular parenchyma is an important predictor of prognosis. However, little attention has been paid to necrosis of ductal epithelium, which may result in disconnection of the main pancreatic duct. In pancreatic duct disconnection, a viable segment of the pancreatic body or tail is isolated from the gastrointestinal tract; the result is a persistent end fistula, that is, an uncontrolled leak of pancreatic secretions into peripancreatic spaces without communication to the gastrointestinal tract. The authors present their experience with clinical and radiologic follow-up of 85 patients with necrotic pancreatitis who either did (n = 46) or did not (n = 39) have pancreatic duct disconnection at surgery. Confident preoperative diagnosis of a disconnected duct requires both imaging tests (computed tomography or magnetic resonance imaging) and pancreatography. However, not all peripancreatic collections signify ductal disconnection, and imaging has poor accuracy in differentiation between pancreatic and peripancreatic necrosis. Early recognition of disconnected pancreatic duct obviates unnecessary and potentially harmful drainage procedures. PMID- 17848699 TI - Complications of liver transplantation: multimodality imaging approach. AB - Liver transplantation is currently an accepted first-line treatment for patients with end-stage acute or chronic liver disease, but postoperative complications may limit the long-term success of transplantation. The most common and most clinically significant complications are arterial and venous thrombosis and stenosis, biliary disorders, fluid collections, neoplasms, and graft rejection. Early diagnosis is crucial to the successful management of all these complications, and imaging plays an important role in the diagnosis of all but graft rejection. A multimodality approach including ultrasonography and cross sectional imaging studies often is most effective for diagnosis. Each imaging modality has specific strengths and weaknesses, and the diagnostic usefulness of a modality depends mainly on the patient's characteristics, the clinical purpose of the imaging evaluation, and the expertise of imaging professionals. PMID- 17848700 TI - MR imaging of the acute abdomen and pelvis: acute appendicitis and beyond. AB - Acute abdominal and pelvic processes account for more than half of all surgical procedures performed in the emergency setting. Rapid and accurate diagnosis in the emergency department is essential for the appropriate management of these acute conditions. Magnetic resonance (MR) imaging is an attractive modality for diagnostic imaging in patients for whom the risks of radiation or the potential nephrotoxicity of iodinated contrast agents is a major concern, such as pregnant and pediatric patients. MR imaging is most useful for evaluating pregnant patients with acute lower abdominal pain believed to have an extra-uterine cause, such as appendicitis or ovarian torsion. Other patients with other conditions commonly seen in the emergency setting may be better evaluated with another cross sectional imaging modality. Imaging protocols should be adapted to the constraints of acute illness, with emphasis placed on minimizing the duration of image acquisition, and should include strategies to decrease motion-related artifacts. A prudent approach is to select the imaging modalities that can best depict a particular subset of clinical conditions to help narrow the differential diagnosis. Disadvantages of MR imaging include its high cost, the limited availability of MR imaging systems and trained radiologists, and the incompatibility of MR imaging systems and the equipment used for intensive care and monitoring of patient status. PMID- 17848701 TI - Abdominal MR imaging at 3.0 T. AB - Magnetic resonance (MR) imaging at 3.0 T offers an improved signal-to-noise ratio compared with that at 1.5 T. However, the physics of high field strength also brings disadvantages, such as increases in the specific absorption rate, in magnetic field inhomogeneity effects, and in susceptibility artifacts. The use of 3.0-T MR imaging for abdominal evaluations, in particular, has lagged behind that for other applications because of the difficulty of imaging a large volume while compensating for respiratory motion. At a minimum, abdominal MR imaging at 3.0 T requires modifications in the pulse sequences used at 1.5 T. Such modifications may include a decrease in the flip angle used for refocusing pulses and an increase in the repetition time for T1-weighted acquisitions. In addition, parallel imaging and other techniques (hyper-echo sequences, transition between pseudo steady states) may be used to maintain a high signal-to-noise ratio while decreasing acquisition time and minimizing the occurrence of artifacts on abdominal MR images. PMID- 17848702 TI - Body MR imaging at 3.0 T: understanding the opportunities and challenges. AB - The development of high-field-strength magnetic resonance (MR) imaging systems has been driven in part by expected improvements in signal-to-noise ratio, contrast-to-noise ratio, spatial-temporal resolution trade-off, and spectral resolution. However, the transition from 1.5- to 3.0-T MR imaging is not straightforward. Compared with body imaging at lower field strength, body imaging at 3.0 T results in altered relaxation times, augmented and new artifacts, changes in chemical shift effects, and a dramatic increase in power deposition, all of which must be accounted for when developing imaging protocols. Inhomogeneities in the static magnetic field and the radiofrequency field at 3.0 T necessitate alterations in the design of coils and other hardware and new approaches to pulse sequence design. Techniques to reduce total body heating are demanded by the physics governing the specific absorption rate. Furthermore, the siting and maintenance of 3.0-T MR imaging systems are complicated by additional safety hazards unique to high-field-strength magnets. These aspects of 3.0-T body imaging represent current challenges and opportunities for radiology practice. PMID- 17848703 TI - Imaging of synovial chondromatosis with radiologic-pathologic correlation. AB - Primary synovial chondromatosis represents an uncommon benign neoplastic process with hyaline cartilage nodules in the subsynovial tissue of a joint, tendon sheath, or bursa. The nodules may enlarge and detach from the synovium. The knee, followed by the hip, in male adults are the most commonly involved sites and patient population. The pathologic appearance may simulate chondrosarcoma because of significant histologic atypia, and radiologic correlation to localize the process as synovially based is vital for correct diagnosis. Radiologic findings are frequently pathognomonic. Radiographs reveal multiple intraarticular calcifications (70%-95% of cases) of similar size and shape, distributed throughout the joint, with typical "ring-and-arc" chondroid mineralization. Extrinsic erosion of bone is seen in 20%-50% of cases. Computed tomography (CT) optimally depicts the calcified intraarticular fragments and extrinsic bone erosion. Magnetic resonance (MR) imaging findings are more variable, depending on the degree of mineralization, although the most common pattern (77% of cases) reveals low to intermediate signal intensity with T1-weighting and very high signal intensity with T2-weighting with hypointense calcifications. These signal intensity characteristics on MR images and low attenuation of the nonmineralized regions on CT scans reflect the high water content of the cartilaginous lesions. CT and MR imaging depict the extent of the synovial disease (particularly surrounding soft-tissue involvement) and lobular growth. Secondary synovial chondromatosis can be distinguished from primary disease both radiologically (underlying articular disease and fewer chondral bodies of variable size and shape) and pathologically (concentric rings of growth). Treatment of primary disease is surgical synovectomy with removal of chondral fragments; recurrence rates range from 3% to 23%. Malignant transformation to chondrosarcoma is unusual (5% of cases) and, although difficult to distinguish from benign disease, is suggested by multiple recurrences and marrow invasion. Recognizing the appearances of primary synovial chondromatosis, which reflect their underlying pathologic characteristics, improves radiologic assessment and is important to optimize patient management. PMID- 17848704 TI - Fourth ventricle epidermoid tumor: radiologic, intraoperative, and pathologic findings. PMID- 17848705 TI - Physics of cardiac imaging with multiple-row detector CT. AB - Cardiac imaging with multiple-row detector computed tomography (CT) has become possible due to rapid advances in CT technologies. Images with high temporal and spatial resolution can be obtained with multiple-row detector CT scanners; however, the radiation dose associated with cardiac imaging is high. Understanding the physics of cardiac imaging with multiple-row detector CT scanners allows optimization of cardiac CT protocols in terms of image quality and radiation dose. Knowledge of the trade-offs between various scan parameters that affect image quality--such as temporal resolution, spatial resolution, and pitch--is the key to optimized cardiac CT protocols, which can minimize the radiation risks associated with these studies. Factors affecting temporal resolution include gantry rotation time, acquisition mode, and reconstruction method; factors affecting spatial resolution include detector size and reconstruction interval. Cardiac CT has the potential to become a reliable tool for noninvasive diagnosis and prevention of cardiac and coronary artery disease. PMID- 17848706 TI - Designing learning experiences. AB - Creation of significant learning experiences follows basic steps of instructional design related to situational factors, goals and objectives, feedback and evaluation methods, teaching and learning activities, alignment of the preceding elements, and course evaluation. Goals should reflect what students will learn at the end of the course and what will still be with them several years later. Objectives should focus on learner performance, not teacher performance, and on behavior, not subject matter; there should be only one learning outcome per objective. Students learn more and retain their knowledge longer if they acquire it in an active rather than a passive manner. The situational factors, goals and objectives, feedback and evaluation, and teaching and learning activities should all reflect and support each other. The act of course evaluation closes the educational loop of design, implement, evaluate, and modify. PMID- 17848707 TI - Next generation web search: augmenting information access for radiologists. PMID- 17848708 TI - SimpleDICOM suite: personal productivity tools for managing DICOM objects. AB - Commercial picture archiving and communication systems (PACS) are adept at supporting mainstream radiology work flow, but radiologists frequently encounter situations requiring additional functionality. For example, the incorporation of foreign or nonradiologic images and the deidentification of examinations for research purposes are useful tasks that do not fall within the purview of most commercial PACS. A suite of free, downloadable, vendor-independent software programs designed as PACS add-ons, the SimpleDICOM (Digital Imaging and Communications in Medicine) Suite, has been developed to aid radiologists in performing these tasks. Clinically relevant software design and informed administrative decisions during deployment allow optimal function of this software suite, which is available for download from the Internet. PMID- 17848710 TI - Bullying as a public health issue. PMID- 17848712 TI - Reprogramming somatic gene activity by fusion with pluripotent cells. AB - Fertilized eggs and early blastomeres, that have the potential to develop to fetuses when placed into a uterus, are totipotent. Those cells in the embryo, that can give rise to all cell types of an organism, but not to an organism itself, are pluripotent. Embryonic stem (ES), embryonic carcinoma (EC), and embryonic germ (EG) cells are powerful in vitro artifacts derived from different embryonic stages and are pluripotent. Totipotent and pluripotent cells have the potential to greatly benefit biological research and medicine. One powerful feature is that the genetic program of somatic cells can be converted into that of totipotent or pluripotent cells, as shown by nuclear transfer or cell fusion experiments. During reprogramming by cell fusion various features of pluripotent cells are acquired. These include the typical morphology of the respective pluripotent fusion partner, a specific epigenetic state, a specific gene profile, inactivation of tissue-specific genes expressed in the somatic fusion partner, and the developmental as well as differentiation potential of pluripotent cells. In this review, we will discuss what is known about the reprogramming process mediated by cell fusion and the potential use of fusion-induced reprogramming for therapeutic applications. PMID- 17848713 TI - Human therapeutic cloning (NTSC): applying research from mammalian reproductive cloning. AB - Human therapeutic cloning or nuclear transfer stem cells (NTSC) to produce patient-specific stem cells, holds considerable promise in the field of regenerative medicine. The recent withdrawal of the only scientific publications claiming the successful generation of NTSC lines afford an opportunity to review the available research in mammalian reproductive somatic cell nuclear transfer (SCNT) with the goal of progressing human NTSC. The process of SCNT is prone to epigenetic abnormalities that contribute to very low success rates. Although there are high mortality rates in some species of cloned animals, most surviving clones have been shown to have normal phenotypic and physiological characteristics and to produce healthy offspring. This technology has been applied to an increasing number of mammals for utility in research, agriculture, conservation, and biomedicine. In contrast, attempts at SCNT to produce human embryonic stem cells (hESCs) have been disappointing. Only one group has published reliable evidence of success in deriving a cloned human blastocyst, using an undifferentiated hESC donor cell, and it failed to develop into a hESC line. When optimal conditions are present, it appears that in vitro development of cloned and parthenogenetic embryos, both of which may be utilized to produce hESCs, may be similar to in vitro fertilized embryos. The derivation of ESC lines from cloned embryos is substantially more efficient than the production of viable offspring. This review summarizes developments in mammalian reproductive cloning, cell-to-cell fusion alternatives, and strategies for oocyte procurement that may provide important clues facilitating progress in human therapeutic cloning leading to the successful application of cell-based therapies utilizing autologous hESC lines. PMID- 17848715 TI - Cellular reprogramming for the creation of patient-specific embryonic stem cells. AB - The success of somatic cell nuclear transfer in mammals has opened the possibility to dedifferentiate cells from a patient into embryonic stem cells and in doing so, potentially generate all different cells and tissues of the human body. These cells could be later transplanted to the same patient without immune rejection. Whereas this principle has been demonstrated in laboratory animals, it is yet to be shown to work in primates. Herein we discuss the probability of somatic cell nuclear transfer becoming a real therapeutic alternative as well as the potential emerging dedifferentiation approaches that may eventually replace it. PMID- 17848716 TI - Cytoplasmic cell fusion: Stembrid technology for reprogramming pluripotentiality. AB - Recent progress in somatic cell nuclear transfer (SCNT) provides the evidence for the presence of reprogramming factors in human embryonic stem cells (hESC). Hybrid hESC with donor human somatic nuclei have been established, but the resulting hybrid hESC contained DNA originating from both hESC and donor somatic cells. There is still no method to completely replace the hESC nuclei by the nuclei of somatic cells and to obtain the pure colonies of hESC with donor genotype. We present here the original technology, which is based on enucleation of h ESC and their fusion with the adult somatic cells, resulting in the establishment of individual-specific hESC with the genotype of the donor somatic cells. The resulting constructs was demonstrated to have the "stemness" of hESC and the genotype of the donor somatic cells. So this "Stembrid technology," may be used for the construction of patient-specific hESC. PMID- 17848714 TI - Interspecies somatic cell nuclear transfer and preliminary data for horse cow/mouse iSCNT. AB - Nuclear transfer (NT) experiments in mammals have demonstrated that adult cells are genetically equivalent to early embryonic cells and the reversal of the differentiated state of a cell to another that has characteristics of the undifferentiated embryonic state can be defined as nuclear reprogramming. The feasibility of interspecies somatic cell NT (iSCNT) has been demonstrated by blastocyst formation and the production of offspring in a number of studies. Embryo and oocyte availability is a major limiting factor in conducting NT to obtain, blastocysts for both reproductive NT studies in genetically endangered animals and in embryonic stem cell derivation for species such as the horse and human. One approach to generate new embryonic stem cells in human as disease models, or in species where embryos and oocytes are not widely available, is to use oocytes from another species. Utilization of oocytes for recipient cytoplasts from other species that are accessible and abundant, such as the cow and rabbit, would greatly benefit ongoing research on reprogramming and stem cell sciences. The use of iSCNT is an exciting possibility for species with limited availability of oocytes as well as for endangered or exotic species where assisted reproduction is needed. However, the mechanisms involved in nuclear reprogramming by the oocyte are still unknown and the extent of the "universality" of ooplasmic reprogramming of development remains under investigation. PMID- 17848717 TI - The status of human nuclear transfer. AB - Human therapeutic cloning is a recently emerged application of somatic cell nuclear transfer (SCNT), which is currently being performed to produce patient specific stem cell lines for future stem cell therapies. The advantages in producing human nuclear transfer (NT) embryos to derive NT stem cell lines are that these can be tailor-made (i.e., are autologous in nature) for the patient and may overcome the need to administer life-long immunosuppression following stem cell transplantation. Although the rationale for using NT embryos is not for reproductive purposes, human NT remains clouded in ethical, moral, and religious controversies. The recent retraction of high-impact factor publications in the field of human NT from a research group in South Korea has placed stem cell research in a delicate situation. These heavily publicized issues may hinder the progress of this research and may threaten to bring current research to a complete halt. This review outlines the recent status of human NT, its continuing progress and the difficulties the field faces. Of most concern are the ethical issues, which surround obtaining human oocytes for research. Recent evidence suggests that failed-to-fertilize oocytes are poor sources for human SCNT, but obtaining fresh, viable oocytes may be even more problematic. The current status of human SCNT is outlined in this review with particular reference made to, lessons learnt from animal research, the oocyte dilemma and optimization of human NT. PMID- 17848718 TI - Epigenetic reprogramming of nuclei using cell extracts. AB - Recent evidence indicates that nuclear and cytoplasmic extracts from undifferentiated cells can reprogram gene expression and promote pluripotency in otherwise more developmentally restricted cell types. Notably, extracts of embryonal carcinoma cells or embryonic stem cells have been shown to elicit a shift in the transcriptional program of target cells to upregulate embryonic stem cell genes, downregulate somatic cell-specific markers, and epigenetically modify histones. Reprogrammed kidney epithelial cells acquire a potential for differentiation toward ectodermal and mesodermal lineages. Cell extract-mediated nuclear reprogramming may constitute an attractive alternative to reprogramming somatic cells by cell fusion or nuclear transfer. This review highlights recent observations leading to the concept that extracts derived from pluripotent cells contain regulatory components capable of reprogramming somatic nuclear function. Limitations of current extract-based reprogramming approaches are also addressed. PMID- 17848719 TI - Epigenetic programming of mesenchymal stem cells from human adipose tissue. AB - Stromal stem cells identified in various adult mesenchymal tissues (commonly called mesenchymal stem cells [MSCs]) have in past years received more attention as a result of their potential interest as replacement cells in regenerative medicine. An abundant and easily accessible source of adult human MSCs are stem cells harvested from liposuction material. Similarly to bone marrow-derived MSCs, human adipose tissue-derived stem cells (ASCs) can give rise to a variety of cell types in vitro and in vivo; however, they have a propensity to differentiate into primarily mesodermal lineages. Even so, their capacity to differentiate into nonadipogenic mesodermal pathways seems to be restricted. Emerging DNA methylation profiles at adipogenic and nonadipogenic gene promoters in freshly isolated, cultured, or differentiated ASCs aim to provide an epigenetic explanation for this restrictive differentiation potential. A review of these studies indicates that human ASCs are epigenetically marked by mosaic hypomethylation of adipogenic promoters, whereas nonadipogenic lineage-specific promoters are hypermethylated. Surprisingly, in vitro differentiation toward various pathways maintains the overall methylation profiles of undifferentiated cells, raising the hypothesis that ASCs are at least epigenetically preprogrammed for adipogenesis. Novel attempts at reprogramming the epigenome of MSCs have been initiated to enhance the differentiation capacity of these cells. PMID- 17848720 TI - Cell fusion for reprogramming pluripotency: toward elimination of the pluripotent genome. AB - Embryonic stem cell (ESC) technology should enable the generation of specific cell types for the study and treatment of human diseases. Therapeutic cloning provides a way to generate ESCs genetically matched to diseased individuals through nuclear reprogramming of the somatic genome. However, practical and ethical limitations associated with therapeutic cloning are calling for the development of oocyte- and-embryo-free alternatives for obtaining of autologous pluripotent cells for transplantation therapy. An alternative approach to reprogram the somatic genome involves fusion between somatic and pluripotent cells. Potential fusion partners with reprogramming activities include embryonal carcinoma cells, embryonic germ cells, and ESCs. Experimental evidence is now available, which demonstrates that mouse and human somatic cells can be reprogrammed by fusion to form pluripotent hybrid cells. Recent progress infusion based reprogramming is reviewed with reference to the developmental potency of hybrid cells as well as genetic and epigenetic correlates of reprogramming. However, hybrid cells lack therapeutic potential because of their abnormal ploidy and the presence of nonautologous genes from the pluripotent parent. We discuss the potential of fusion-based reprogramming for the generation of diploid, autologous pluripotent cells using two alternative routes: the enucleation of ESCs and the fusion of such cytoplasts to somatic cell karyoplasts or intact somatic cells, and the selective elimination of the pluripotent genome following fusion to the somatic partner. Finally, these approaches are discussed in the light of recent progress showing that overexpression of embryonic transcription factors can restore a state of pluripotency to somatic cells. PMID- 17848721 TI - The potential of cell fusion for human therapy. AB - As donor organs and tissues for transplantation medicine are scarce, alternative methods for replacing damaged cells or restoring organ function are highly needed. Here, we consider the therapeutic potential of cell fusion. After highlighting the various contexts in which cells are known to fuse during mammalian development, we discuss the implications of the observation that cell fusion can occur with restorative effects following tissue damage or cell transplantation. There are still, however, many challenges facing those who wish to implement cell fusion as a therapeutic tool. These include identifying the best cells to use for reparative fusion, determining the best route of introducing these cells into the desired tissue, discovering methods to increase the incidence of cell fusion, and ensuring the functionality of the resulting fusion products. If these difficulties can be overcome, cell fusion might have therapeutic potential as highlighted by several recent transplantation studies. PMID- 17848722 TI - The future of human nuclear transfer? PMID- 17848724 TI - Associations of calcium and magnesium in serum and hair with bone mineral density in premenopausal women. AB - BACKGROUND AND AIMS: Some minerals have been associated with bone mineral density (BMD) in postmenopausal women or people with certain chronic diseases, but the results have been inconsistent. This study aimed to evaluate the association of serum and hair levels of calcium and magnesium with BMD in premenopausal women. METHODS: This cross-sectional study of 104 premenopausal volunteers recruited from out-patient clinics and a health promotion center in a university hospital in Seoul, Korea evaluated the association of serum and hair minerals with BMD in premenopausal women. All participants completed BMD measurements at the spine and hip and provided hair for calcium and magnesium analysis; blood was obtained from 68 of these participants for serum analysis. RESULTS: Higher serum magnesium was associated with lower BMD at the spine (P = 0.047), but a higher hair magnesium was associated with higher BMD at the spine (P = 0.024). The ratio of serum calcium to magnesium was positively associated with BMD at the spine (P = 0.017). CONCLUSIONS: Magnesium in serum and hair was associated with BMD in premenopausal women. The ratio of serum calcium to magnesium appears to be a significant indicator of BMD. PMID- 17848725 TI - Copper concentration in body tissues and fluids in normal subjects of southern Poland. AB - Data on the concentration of the elements in the human body are important, for example, to estimate the amounts required to maintain a good healthy state or find their connections with morbidity and mortality. In this paper, the concentration of copper (by flame atomic absorption spectrometry) in material obtained from autopsy cases of nonpoisoned people (n = 130), aged from 14 to 80 years, between 1990-2006, is presented. The following values were found (mean +/- SD in micrograms of copper per gram or per milliliter): brain 3.32 +/- 1.50 (n = 43), liver 3.47 +/- 1.51 (n = 79), kidney 2.15 +/- 0.90 (n = 76), stomach 1.10 +/ 0.76 (n = 65), intestines 1.54 +/- 1.19 (n = 25), lung 1.91 +/- 1.30 (n = 27), spleen 1.23 +/- 0.28 (n = 3), heart 3.26 +/- 0.59 (n = 5), bile 3.60 +/- 1.67 (n = 13), and blood 0.85 +/- 0.19 (n = 73). PMID- 17848726 TI - Contribution to the data on copper concentration in blood and urine in patients with Wilson's disease and in normal subjects. AB - Determination of copper in human tissues and body fluids may be crucial in the diagnosis of Wilson's disease. In this study we evaluated urinary copper excretion and urine and blood concentration in 14 patients in whom Wilson's disease was confirmed (group A) and in 21 subjects in whom the disease was only suspected (group B). The following values (mean +/- SD) were found: 24-h urine (microg Cu/24 h), 152 +/- 135 (A) and 31.8 +/- 10.9 (B); urine (microg Cu/ml), 0.091 +/- 0.087 (A) and 0.028 +/- 0.011 (B); and blood (microg Cu/ml), 0.62 +/- 0.25 (A) and 0.72 +/- 0.09 (B). By comparison, urine copper concentration in the group of apparently healthy subjects was 0.035 +/- 0.010 (n = 50), and blood copper concentration in autopsy cases of nonpoisoned people was 0.85 +/- 0.19 (n = 73). PMID- 17848727 TI - Serum levels of zinc, copper, iron, cobalt, magnesium, and selenium elements in children diagnosed with Giardia intestinalis and Enterobiosis vermicularis in Hatay, Turkey. AB - The intestinal parasites are noted to be an important health problem in Turkey as similarly reported in the globe. The aim of this study was to investigate the changes in total content of essential elements, namely, zinc, iron, copper, cobalt, magnesium, and selenium, in children infected with intestinal parasites aged between 6 and 12 years inhabiting in Hatay Province, Turkey. These essential elements were measured in the children/patient who was positive for intestinal parasites, Giardia intestinalis and Enterobius vermicularis. Scores were obtained from the positive study group (SG), and their age matched the healthy children control group (CG). Serological levels of zinc, iron, copper, cobalt, magnesium, and selenium were analyzed by Varian Liberty Series II inductively coupled plasma atomic emission spectrometer (ICP-AES). The mean magnesium concentrations were found to be statistically different at 95% confidence interval level between study groups. As a result of this study, selenium was found to be uncorrelated with all other elements examined; whereas, copper was observed to have statistically significant correlations with cobalt, magnesium, and zinc. In addition, cobalt-magnesium, cobalt-zinc, and magnesium-zinc metal pairs were found to have statistically significant correlations based on study findings. PMID- 17848728 TI - In vitro effects of calcium fructoborate on fMLP-stimulated human neutrophil granulocytes. AB - Discovery of naturally occurring boron complexes with organic compounds containing hydroxyl groups, sugars, and polysaccharides, adenosine-5-phosphate, pyridoxine, riboflavin, dehydroascorbic acid, and pyridine nucleotides led to the reassessment of the biochemical role of boron. Boron's anti-inflammatory actions were claimed but not yet demonstrated. This study investigated the effects of calcium fructoborate (CF) on the human polymorphonuclear neutrophils (PMN) that play a central role in the inflammatory response. Our results demonstrated that CF exposure induced a dose-dependent decrease in cell viability. Treatment of PMN cells, for 24 h, with 22,500 microM CF led to a decrease in cell viability by 61.1%, an inhibition of respiratory burst by 92.9% in the case of fMLP-stimulated cells, a diminution of intracellular level of superoxide anion with 59.3%, and a stimulation of superoxide dismutase activity by 72% in unstimulated PMN cells. Altogether, these results suggest the antioxidant and anti-inflammatory properties of CF. PMID- 17848729 TI - Serum concentration of copper, zinc, iron, and cobalt and the copper/zinc ratio in horses with equine herpesvirus-1. AB - The serum concentrations of copper, zinc, iron, and cobalt and copper/zinc ratio were investigated in horses infected with equine herpesvirus-1 (EHV-1). Nine horses were naturally infected with the virus and nine healthy horses served as controls. The concentrations of copper, zinc, iron, and cobalt were determined spectrophotometrically in the blood serum of all horses. The results were (expressed in micrograms per deciliters) copper 2.80 +/- 0.34 vs 1.12 +/- 0.44, zinc 3.05 +/- 0.18 vs 0.83 +/- 0.06, iron 2.76 +/- 0.17 vs 3.71 +/- 0.69, cobalt 0.19 +/- 0.37 vs 0.22 +/- 0.45, and copper/zinc ratio 0.72 +/- 0.38 vs 1.41 +/- 0.36 for control vs infected group, respectively. In conclusion, copper and zinc concentrations of the infected group were lower than the control group (p < 0.001), whereas iron concentration and the copper/zinc ratio of the infected group were higher than the control group (p < 0.05 and p < 0.001). The cobalt concentration was not found to be statistically different between two groups. It might be emphasized that copper/zinc ratio was significantly affected by the EHV 1 infection, so it could be taken into consideration during the course of infection. PMID- 17848730 TI - Protective effects of erdosteine and vitamins C and E combination on ischemia reperfusion-induced lung oxidative stress and plasma copper and zinc levels in a rat hind limb model. AB - The aim of this study was to investigate the protective effects of erdosteine and vitamins C and E (VCE) on the lungs after performing hind limb ischemia reperfusion (I/R) by assessing oxidative stress, plasma copper (Cu), and zinc (Zn) analysis. The animals were divided randomly into four groups as nine rats each as follows: control, I/R, I/R plus erdosteine, and I/R plus VCE combination. I/R period for 60 min was performed on the both hind limbs of all the rats in the groups of I/R, erdosteine with I/R, VCE with I/R allowing 120 min of reperfusion. The animals received orally erdosteine one time in a day and 3 days before I/R in the erdosteine group. In the VCE group, the animals VCE combination received one time in a day and 3 days before I/R, although placebo was given to control and I/R group animals. Lung lipid peroxidation (malondialdehyde [MDA]) level, superoxide dismutase (SOD), and catalase activities were increased, although lung glutathione (GSH) and plasma Zn levels decreased in I/R group in lung tissue compared with the control group. Serum MDA level, creatine kinase, and lactate dehydrogenase activities were increased in I/R group compared with the control. Lung MDA and plasma Zn levels and lung SOD activity were decreased by erdosteine administration, whereas lung GSH levels after I/R increased. The plasma Zn levels and lung SOD activity were decreased by VCE administration, although the plasma Cu and lung GSH levels increased after I/R. In conclusion, erdosteine has an antioxidant role on the values in the rat model, and it has more protective affect than in VCE in attenuating I/R-induced lung injury in rats. PMID- 17848731 TI - Fructose consumption and moderate zinc deficiency influence growth and adipocyte metabolism in young rats prone to adult-onset obesity. AB - The effects of low zinc, high fructose diet on growth and adipocyte metabolism were examined in rats. At 28 days of age, animals were assigned to diets either adequate in zinc (30 ppm) with water (AZW) or fructose solution (AZF), or low in zinc (5 ppm) with water (LZW) or fructose solution (LZF). Body weight and food and fructose solution intake were measured three times a week. Blood samples were collected at baseline, 4 weeks, and 8 weeks, and energy expenditure was measured. The rats were killed at 12 weeks. Adipocytes were cultured in medium containing C14-glucose and physiological insulin concentrations. The animals in the LZF group consumed less energy and gained less weight than the other groups. Serum zinc concentrations were lower in the LZF than the AZF group. Energy expenditure over a 24-h period did not differ between groups; however, the respiratory quotient in the fed state was higher in the groups consuming fructose solution than in those consuming water. The mesenteric adipocytes from the animals in the LZF group utilized more glucose. Thus, the addition of fructose to a LZ diet reduced energy intake and growth and altered adipocyte fuel metabolism in young growing rats. PMID- 17848732 TI - Effect of supplemental dietary zinc on the mammalian target of rapamycin (mTOR) signaling pathway in skeletal muscle and liver from post-absorptive mice. AB - Zinc (Zn) is an essential trace element that functions in cellular signaling. The mammalian target of rapamycin (mTOR) regulates the initiation of protein synthesis. The objective of this study was to determine whether Zn could stimulate protein phosphorylation in the mTOR pathway in vivo. Mice (C57BL/6J, n = 30) were fed Zn marginal diets (ZM, 5 mg/kg) for 4 weeks, followed by fasting (F) and/or refeeding with ZM or Zn supplemental (300 mg/kg, ZS) diets for 3 or 6 h. Plasma insulin was greater (P < 0.05) in refed animals as compared to F animals. Protein phosphorylation was detected using multiplex analysis and Western blotting. Multiplex analysis indicated greater (P < 0.05) p70 S6 kinase (p70S6K) and glycogen synthase kinase 3 (GSK-3 alpha/beta) phosphorylation in livers from 6-h refed ZS animals as compared to F animals. Western blots indicated increased (P < 0.05) Akt (Ser 473) phosphorylation in skeletal muscle from animals refed ZS diets for 3 and 6 h as compared to F animals. The ZS diet affected phosphorylation of GSK-3 (alpha/beta) in liver, as 3-h ZS refed animals had greater (P < 0.01) phosphorylation than F animals. These findings indicate that Zn may contribute to the initiation of protein synthesis as a signaling molecule in vivo. PMID- 17848733 TI - Gender difference in the influence of antioxidants on the blood-brain barrier permeability during pentylenetetrazol-induced seizures in hyperthermic rat pups. AB - Our purpose in this study was to investigate the protective effects of selenium and vitamin E on the blood-brain barrier (BBB) permeability in rats with convulsion under hyperthermic conditions. To eliminate the effect of sex on BBB, we performed our study on 4- to 5-week-old prepubertal rat pups. Evans-blue was used as a BBB tracer. Convulsions were induced by administration of i.p. pentylenetetrazol. In the selenium group, 4 ppm selenium was added to the drinking water for 4-5 weeks. Vitamin E was administered at 700 mg/kg ip. It was shown that the convulsions, both under normothermic and hyperthermic conditions, caused widespread increase in the BBB permeability (p < 0.05). In addition, a significant difference was observed among female and male rats (f [1, 102] = 6.387, p < 0.05). In convulsions under normothermic conditions, there was a further increase in the BBB permeability (F[3, 102] = 43.534, p < 0.001) and a greater increase of permeability in males compared to females (F[1, 102] = 6.387, p < 0.05). Selenium and vitamin E significantly decreased the BBB destruction caused by convulsions under hyperthermic conditions in males (p < 0.05). Treatment with selenium or vitamin E has beneficial effects on the BBB breakdown during convulsions. But gender differences are very important in BBB permeability under pathological conditions and antioxidant treatments. PMID- 17848734 TI - Mimosine mitigates oxidative stress in selenium deficient seedlings of Vigna radiata--Part I: Restoration of mitochondrial function. AB - Mimosine, a non-protein plant amino acid found in Mimosa pudica and certain species of Leucaena, was beneficial for the growth of seedlings of Vigna radiata germinated under selenium-deficient stressed condition (-Se stressed) despite the recognized toxicity of the allelochemical. Exposure of mimosine at 0.1 mM (Mim 0.1) promoted the growth of the seedlings and significantly enhanced mitochondrial functional efficiency. Growth-related parameters including root and shoot lengths and dry weight were increased by 44-58% in the Mim-0.1 group compared to that of the -Se-stressed group. Oxygen uptake by mitochondria of Mim 0.1 group, studied with different substrates, revealed enhanced State 3 respiratory rates with regulated State 4 rates, resulting in high respiratory control ratio (RCR) of 3.4 to 3.9 indicative of a high degree of oxidative coupling. Specific activities of mitochondrial electron transport enzymes, nicotinamide adenine dinucleotide (reduced form) (NADH)-cytochrome (cyt) c oxidoreductase, succinate dehydrogenase, and cyt c oxidase in the Mim-0.1 group were enhanced by 53% to threefold over those of the Se-stressed group. Marked decreases in the extent of mitochondrial lipid peroxidation ensued upon mimosine exposure, indicative of its antioxidant function. Mitochondrial 45Ca2+ uptake was notably augmented twofold in the Mim-0.1 group, compared to the Se-stressed group. Detailed kinetic analyses of Ca2+ uptake revealed positive cooperative interactions in both -Se-stressed group and Mim-0.1 groups with Hill coefficient (nH) values of 1.7 and 2, respectively. The present study establishes the beneficial effects of mimosine exposure at 0.1 mM on the growth and mitochondrial function of the seedlings grown under selenium-deficient stressed condition and a significant physiological role can be ascribed to mimosine. PMID- 17848735 TI - The management of posttransplant lymphoproliferative disorder. AB - Posttransplant lymphoproliferative disorder (PTLD) is a life-threatening complication of allogeneic hematopoietic stem cell and solid organ transplantation. Most cases are EBV-positive B-cell neoplasms, which occur in the setting of pharmacologically impaired cellular immunity. Several different treatment strategies including cytotoxic antitumor therapy, anti-B-cell monoclonal antibody therapy, antiviral therapy, and modalities aimed at restoration of EBV-specific cellular immunity have been employed. In addition, efforts to identify patients at high risk for PTLD have resulted in attempts at prophylactic and preemptive therapies. In this review we discuss the available literature on differing approaches to PTLD management, identify areas in need of further investigation, and, when possible, make general recommendations. Reduction of immunosuppression remains the mainstay of first-line treatment. Accumulating evidence supports the role of rituximab as second-line therapy with cytotoxic chemotherapy reserved for specific circumstances. Further investigations are needed to better define the role of more novel and less widely available therapies such as the adoptive transfer of EBV-specific T cells and optimization of antiviral therapies. PMID- 17848737 TI - Phase I/II study of IV topotecan in combination with whole brain radiation for the treatment of brain metastases. AB - A phase I/II trial was conducted to determine the toxicities and efficacy (overall response, overall survival, and progression-free survival) of the combination of topotecan and whole brain radiation therapy (XRT) in patients with brain metastases. Patients received 30 Gy XRT given in 10 fractions to the whole brain. In phase I, patients were treated in groups of three at each topotecan dose level; dose escalation proceeded until the maximum tolerated dose (MTD) was identified. The dose-limiting toxicity proved to be grade IV neutropenia at 0.6 mg/m2/d, resulting in an MTD of 0.5 mg/m2/d. One of nine patients showed a response to treatment, and that was partial (OR 11%). Three had stable disease (33%), and four experienced progressive disease (44%). Median progression-free survival was 60 d; median overall survival was 102 d. Intravenous topotecan at 0.5 mg/m2/d concomitant to XRT with 30 Gy in 3-Gy fractions is tolerable in patients with brain metastases. This regimen has the additional advantage of providing systemic treatment to patients with metastases in other locations while whole brain radiation is in progress. Although response and survival outcomes in this small study do not appear higher than expected from historical controls, these were not primary end points, and larger studies on this topic would be useful to elucidate the efficacy of this combination treatment regimen. PMID- 17848736 TI - A general review of the role of irinotecan (CPT11) in the treatment of gastric cancer. AB - BACKGROUND: The prognosis of gastric tumor is generally poor because most tumors are diagnosed at an advanced stage. Chemotherapy has a proven palliative role in advanced gastric cancer and several combination regimens were explored in the last 10 yr. Nevertheless, none of them showed a convincing improvement resulting in an enhancement of response rate and overall survival without discrimination of the quality of life. Irinotecan (CPT11) has been evaluated in multiple trials alone or in combined therapy with promising results and good tolerance. Thus, a review of the importance and impact of CPT11 in this indication is detailed. METHODS: This article reviews the evidence for the use of CPT11 in the treatment of gastric cancer based on a computerized MEDLINE search of literature published until August 2006 leading to a total of 91 publications. RESULTS: CPT11 was frequently used and showed a good response rate varying from 14% to 23% as single agent and 45% to 70% in combination with a median time to progression of 3 mo in single agent and 4-6 mo in combination, and median overall survival of approx 7 mo in single agent and up to 10.58 mo in combination. CONCLUSION: The overall response of irinotecan-based chemotherapy in advanced gastric cancer was shown to be as effective as other combined chemotherapy. The hematological and digestive toxicity were tolerable and mild, especially in weekly regimen. Thus, irinotecan based chemotherapy should be considered as one of the preferred choices in front line chemotherapy in advanced gastric cancer. PMID- 17848738 TI - Risk factors for central nervous system metastasis in patients with metastatic breast cancer. AB - AIMS: Patients with metastatic breast cancer (MBC) and central nervous system (CNS) involvement have an impaired survival and quality of life. In this study, we investigated the risk factors for CNS metastasis among patients with MBC. METHODS: The risk factors for development of CNS metastasis were analyzed in 154 patients with MBC. Expression of c-erbB-2, Ki-67, p53, and hormone receptors was examined by immunohistochemistry (IHC) in breast cancer tissue samples from the 154 patients. Kaplan-Meier and log-rank tests were used for the analysis of overall survival (OS). Chi-square test was used for univariate analysis. RESULTS: Median OS was significantly poorer for patients with CNS metastasis as compared with patients with no CNS metastasis (OS, 23 mo vs 30 mo, respectively;p = 0.03). Ki-67 and p53 overexpressions by IHC, and lung metastasis as the first site of relapse, were associated with a higher risk of developing CNS metastasis in the univariate analysis (p 0.05). CONCLUSIONS: Our results show that a high level of c-kit expression occurs frequently in invasive breast cancer, and its expression is associated with ER but unrelated to other clinico-pathological variables. PMID- 17848741 TI - Long-term complications of platinum-based chemotherapy in testicular cancer survivors. AB - The purpose of this study was to describe the rates of cardiovascular and other medical complications related to the use of platinum-based chemotherapy in American testicular cancer survivors. The study sample consisted of 143 eligible long-term testicular cancer survivors. Participants were interviewed, their medical records were reviewed, and blood was obtained for cholesterol measurement during their follow-up visit. The mean follow-up time was 8.4 yr, and their mean age at follow-up was 41.2 yr; 72.7% had had non-seminoma, and 82.5% had received platinum-based chemotherapy. Hypertension rates in the platinum-treated group increased significantly from baseline to follow-up; however, once adjusted for blood pressure measurement (undiagnosed hypertension), no such increase was seen, and hypertension rates were already higher than national estimates at baseline in all groups. At the follow-up visit, the rates of hyperlipidemia (adjusted for measured cholesterol level) in both platinum- and non-platinum-treated groups (28.4% and 37.5%, respectively) were higher than national estimates (16.9%). Rates of coronary artery disease were higher in those who had received platinum and radiation (11.1%) than in those who had received platinum alone (4.3%), but this difference was not statistically significant. As suggested by previous studies, platinum-based chemotherapy may be associated with hypertension, hyperlipidemia, and coronary artery disease. However, our data suggest that undiagnosed hypertension and hyperlipidemia may be significant confounders, and we also observed a trend toward lower testosterone levels in participants who experienced cardiovascular complications. PMID- 17848742 TI - Inhibitory effects of a nutrient mixture on human testicular cancer cell line NT 2/DT matrigel invasion and MMP activity. AB - Current treatment of testicular cancer is associated with secondary malignancy, infertility, and cytotoxicity. Based on reported antimetastatic potential, we investigated the effect of a nutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid, and green tea extract on human testis cancer cell line NT 2/DT by measuring cell proliferation/cytotoxicity, modulation of MMP-2 and MMP 9 secretion, and cancer cell invasive potential. Human testis cancer cells NT 2/DT (ATCC) were grown in DME medium. At near confluence, the cells were treated with NM dissolved in media and tested at 0,10, 50, and 100 microg/mL in triplicate at each dose. Cells were also treated with PMA 200 ng/mL to study enhanced secretion of MMP-9. Cell proliferation/cytotoxicity was evaluated by MTT assay, MMP activity by gelatinase zymography, and invasion through Matrigel. The nutrient mixture showed no significant effect on testis cancer cell growth. Zymography demonstrated secretion of MMP-2 by untreated human testis cancer cells and MMP-9 with PMA induction. NM inhibited secretion of both MMPs in a dose dependent fashion with virtual total inhibition of MMP-9 at 100 microg/mL. Invasion of human testis cancer cells through Matrigel was reduced by 84% at 50 microg/mL and at 100 microg/mL (p = 0.004). NM significantly inhibited MMP secretion and matrix invasion in testicular cancer cells without toxic effect, indicating potential as an anticancer agent. PMID- 17848743 TI - Bispecific antisense oligonucleotides having binding sites directed against an autocrine regulated growth pathway and bcl-2 for the treatment of prostate tumors. AB - Antisense oligonucleotides (oligos) against transforming growth factor-alpha (TGF alpha) (MR1) and its binding site, the epidermal growth factor receptor (EGFR) (MR2), are efficacious against PC-3 and LNCaP prostate tumors. To enhance activity and aid in simultaneous delivery, "bispecific" 39-mer oligos were constructed containing portions of both MR1 and MR2 sequences. The first pair contained truncated sequences recognizing TGF-alpha and EGFR mRNA binding sites, about their respective AUG initiation codons. These bispecifics differ in their 5' to 3' tandem orientation (TGF-alpha/EGFR [MR12] and EGFR/TGF-alpha [MR21] sequences). A second pair was constructed having complementary sequences for EGFR and bcl-2 (EGFR/bcl-2 [MR24] and bcl-2/EGFR [MR42]). All bispecifics were tested in vitro against PC-3 and LNCaP prostate tumor cells, and compared to mono specific oligos from which they were derived. The purpose of this study was: (1) to evaluate bispecific antitumor activity; (2) to identify dominant sequences; (3) to identify effects of binding site orientation; and (4) to determine whether bispecifics are more effective when targeting one versus different growth dependent pathways. Comparisons were made between oligos tested against either PC 3 or LNCaP cells incubated for 2 d with the agents followed by 2 d in their absence. The first PC-3 cell experiment demonstrated that bispecific MR12 and MR21 oligos are at least as effective as their mono-specific counterparts and that the MR21 bispecific orientation is more effective than the MR1 mono-specific by 64% (p = 0.014). It also suggested that the sequence directed against EGFR contributed most to bispecific activity, particularly in the MR21 orientation. In a second PC-3 study a second bispecific pair of 37-mer oligos was constructed containing bases complementary to mRNA encoding EGFR and the apoptosis-associated protein bcl-2 (MR4). MR24 was constructed with the EGFR complementary site at the 5' end (EGFR/bcl-2), and MR42, containing the opposite orientation (bcl-2/EGFR). Each contained the dominant EGFR activity identified previously. MR1, MR2, MR4, MR12, MR21, MR24, and MR42 (1X and 2X in concentration) were cultured with cells and compared to controls. Each oligo significantly inhibited growth of PC-3 cells. MR42 was most effective and significantly better than MR1 (p = 0.0128), MR2 (p = 0.021), MR4 (p = 0.0002), and MR12 (p = 0.0032). 2X MR24 and 2X MR42 were better than their 1X concentration counterparts, but the differences were not significant. In a similar experiment MR1, MR2, MR4, MR12, MR21, MR24, and MR42 were cultured with LNCaP cells and compared to lipofectin-containing controls. Each oligo significantly inhibited the growth of LNCaP cells. Again, MR42 was most effective and significantly better than MR2 (p = 0.021) and MR4 (p = 0.038). MR24 was significantly better than MR2 (p = 0.048). Bispecific oligos are a significant advance in antisense technology and could play a role in treating prostate cancer, particularly if combined with traditional chemotherapeutics. PMID- 17848744 TI - Thymic epithelial neoplasia: a study of 58 cases. AB - Primary thymic epithelial neoplasms (PTENs) are uncommon tumors of anterior mediastinum with a broad range of biological characteristics. We retrospectively reviewed 58 consecutive patients with a diagnosis of PTENs that were confirmed pathologically during 28 yr. There were 58 patients, 31 males (53.4%) and 27 females (46.6%), with a mean age of 43.6 +/-13.8 yr (range, 17-73 yr). Twenty-one (36.2%) patients presented at the Masaoka stage I, 13 (22.4%) patient at stage II, 18 (31.0%) patient at stage III, and 6 (10.4%) patients at stage IV. Forty five (77.7%) patients had myasthenia gravis, 1 (1.7%) immune deficiency, 1 (1.7%) pancytopenia, and 1 (1.7%) nephrotic syndrome. No paraneoplastic syndrome was associated in 10 (17.2%) patients. Complete resection was accomplished in 41 (70.7%) patients, while incomplete resection was performed in 8 (13.8%) patients. In nine (15.5%) patients only biopsy was carried out. Radiotherapy was administered to 19 (32.8%) patients. Eleven (19.0%) out of 58 who presented at advanced stages (at least III) received chemotherapy. Median follow-up period was 59 mo (range, 1-278 mo). During the follow-up period, 17 deaths occurred. Five patients (29.4%) died of tumor-related causes, and the remaining 12 patients died of other causes (cardiovascular diseases [n = 1, 5.9%], sepsis [n = 4, 23.5%], and MG-related respiratory insufficiency [n = 7, 41.2%]). The overall survival rates at 5 yr and 10 yr were 63.9% and 54.2%, respectively. Tumor-related survival rates at 5 yr and 10 yr were 89.0% and 83.2%, respectively. In our series, disease stage, presence or absence of myasthenia gravis, and tumor size did not affect survival (p> 0.05), either. Complete resection of the tumor seems to be the best predictive factor for long-term survival. PMID- 17848745 TI - Outcomes of primary thyroid non-Hodgkin's lymphoma: a series of nine consecutive cases. AB - Primary non-Hodgkin's lymphoma (NHL) of the thyroid gland is a rare disease with an incidence of 0.5 per 100,000 population. Stages IE and IIE thyroid NHL have been traditionally treated by surgical resection; however, modern treatment consists of chemotherapy and local radiotherapy, and surgery is often reserved for tissue diagnosis and relief of airway compression. We retrospectively reviewed the management and outcomes of nine consecutive patients with thyroid NHL, eight females and one male (median age 63 yr, range 34-71 yr) treated between 1994 and 1999. Five patients had disease stage IE and 4 stage IIE. Median follow-up was 72 mo. Pathohistology and immunohistochemistry identified two patients with mucosa-associated lymphoid tissue (MALT), three follicular center cell lymphoma (FCC), two patients large B-cell lymphoma (BLCL), one a marginal zone lymphoma (MZL), and one patient a peripheral T-cell lymphoma (PTCL). Total thyroidectomy was performed in three patients and subtotal thyroidectomy in four. One (MALT) patient underwent surgery alone; three patients surgery, radiotherapy, and chemotherapy (two FCC, one PTCL); three patients surgery and chemotherapy (one MALT, one FCC, one LBCL); and two chemotherapy alone (one LBCL, one MZL). Median survival was 79 mo (range 13-124 mo). The PTCL patient, a 34-yr-old man, died from disseminated disease at 13 mo despite secondary chemotherapy, and one LBCL patient with extensively invasive local disease died from stroke 17 mo after diagnosis. The remaining seven patients remain in remission with no local or systemic relapse at a mean of 86 mo. With appropriate therapy primary thyroid NHL has a favorable course; however, prognosis depends on the histology, local spread, and the stage of the disease at presentation, as well as the patient's performance status. Surgery in combination with chemotherapy and/or radiotherapy is still warranted for intermediate and high-grade thyroid NHLs, with over 77% of patients achieving long-term remission. Peripheral T-cell lymphoma carries a poor prognosis. PMID- 17848746 TI - Naturally produced extracellular matrix inhibits growth rate and invasiveness of human osteosarcoma cancer cells. AB - Enhanced supplementation with certain naturally occurring nutrients and vitamins has been associated with a reduction in occurrence and progression of human cancer. The exact mechanisms of this action are still under investigation. Extracellular matrix (ECM) plays a key role in the development of cancer. Therefore, we studied whether nutrients could exert anticancer effects through alteration of ECM biological properties. Confluent cultures of normal human dermal fibroblasts were allowed to produce and deposit ECM during a 7 d incubation period in the presence of tested compounds. Subsequently, fibroblasts were removed and the growth rates of freshly placed cultures of human osteosarcoma cells (lines U2-OS, MMNG, or SK.ES1) on pre-formed ECM were assayed in plain cell growth medium. In addition, ECM was deposited by fibroblasts on the upper surface of a porous plastic membrane and the subsequent migration of osteosarcoma cells to the other side was assayed in non-supplemented medium. The results demonstrated that the ECM produced by normal fibroblasts treated with a mixture of ascorbic acid, lysine, proline, arginine, cysteine, and green tea polyphenols significantly reduced the growth rate and invasive activity of osteosarcoma cells in contrast to the non-supplemented control. The changes in ECM properties were accompanied by significant changes in ECM protein and glycosaminoglycan composition as assayed immunochemically. We conclude that anticancer effects of nutrients involve beneficial changes in ECM biological properties. The role of ECM components in ECM-dependent regulation of tumor cell activities is discussed. PMID- 17848747 TI - CEA levels in serum and BAL in patients suffering from lung cancer: correlation with individuals presenting benign lung lesions and healthy volunteers. AB - BACKGROUND: Carcinoembryonic antigen (CEA) is a tumor marker belonging to the immunoglobulin gene superfamily of adhesion molecules. CEA is synthesized by epithelial and tumor cells. In this study, CEA levels in sera and bronchoalveolar lavage fluid (BAL) were measured in patients with malignant lung cancer and benign lung diseases. METHODS: In the present study CEA was measured in serum using IRMA methods and in bronchoalveolar lavage of individuals undergoing fiberoptic bronchoscopy. Fifty patients with lung cancer (G1), 20 patients with benign lung lesions (G2), and a control group consisted of 20 individuals (G3) were enrolled in the study. RESULTS: We found that serum CEA levels were significantly higher in G1 compared to G2 and G3 (p < 0.01). No significant difference in serum CEA levels was found between smokers and nonsmokers in any of the three groups studied. CEA was significantly higher in G1 BAL (p < 0.05) compared to G2 and G3 BAL. Furthermore, a statistically significant difference was found in CEA levels in BAL between smokers and nonsmokers of G2. CONCLUSIONS: CEA levels in BAL of normal individuals may be influenced by smoking and other factors that affect lung epithelial cell function. Thus, CEA measurement in BAL alone has little value in the diagnosis of malignancy. BAL CEA levels in smokers of G2 are found significantly higher compared with nonsmokers of the same group and healthy individuals. Smokers of G2 have to be followed up carefully for the possibility of lung cancer growth. PMID- 17848748 TI - Antitumor effect of zoledronic acid in previously untreated patients with multiple myeloma. AB - Bisphophonates are the treatment of choice to prevent skeletal events in patients with multiple myeloma. Some preclinical studies suggested that bisphophonates can be useful as antitumor drugs in some malignancies. We conducted a controlled clinical trial to assess if zoledronic acid can have this clinical activity. Ninety four patients with previously untreated multiple myeloma were treated with a conventional chemotherapy program: cyclophosphamide, vincristine, melphalan, and prednisone (CVMP) and were randomized to received either zoledronic acid (4 mg, iv, every 28 d) or not (control group). The end-point of the present study was to assess improvement in outcome, measured by event-free survival (EFS) and overall survival (OS), and the second-end point was to confirm the efficacy in preventing skeletal events. In an intent-to-treat analysis, all patients were available for efficacy and toxicity. Median follow up was 49.6 mo (range: 34-72 mo). Five year actuarial curves showed that EFS was 80% in the zoledronic acid group, which was statistically different from 52% in the control group (p < 0.01). Actuarial 5 yr OS was 80% in the zoledronic acid arm, and 46% in the control group (p < 0.01). Sketeletal events were more frequent in the control group when compared to zoledronic acid. Toxicity was mild. We confirm the efficacy of zoledronic acid to prevent skeletal events, but we felt that we can demonstrate that zoledronic acid has a clinical antitumor effect measured from a increase in complete response rate and EFS and OS that were better when compared with the control group. We began a controlled clinical trial with modern treatment (including transplant procedures) in combination with zoledronic acid to define the role of zoledonic acid in this setting of patients. PMID- 17848749 TI - Inhibition of glioma cell line A-172 MMP activity and cell invasion in vitro by a nutrient mixture. AB - Standard multimodality therapy of gliomas is associated with poor patient survival and significant toxicity. Abnormal expression of matrix metalloproteinases is associated with tumor growth and invasion. Based on reported antitumor properties, we investigated the effect of a combination of natural compounds (NM), primarily composed of lysine, proline, ascorbic acid, and green tea extract in vitro on glioma cell line A-172, by measuring MMP secretion, invasion through Matrigel, and cell proliferation. Glioma cells A-172 (ATCC) were grown in modified Dulbecco's Eagle medium with 10% fetal bovine serum and antibiotics and treated with NM at 0, 10, 50, 100, 500, and 1000 microg/mL concentration in triplicate at each dose. Cell proliferation was assayed by MTT, MMP secretion by zymography, invasion through Matrigel, and morphology by H&E staining. Zymography showed one band corresponding to MMP-2, which was inhibited by NM in a dose-dependent fashion, with virtual total inhibition at 500-microg/mL concentration. Invasion through Matrigel was completely inhibited at 1000 microg/mL NM. NM was not toxic to glioma cell line A-172 at lower concentrations and exhibited toxicity of 50% over the control at 1000 microg/mL. NM significantly inhibited MMP secretion and invasion-important parameters for cancer prevention, suggesting a possible therapeutic role. PMID- 17848750 TI - Concurrent gemcitabine and radiotherapy for locally advanced pancreatic cancer. AB - This study is designed to assess the toxicity and therapeutic effectiveness of concurrent gemcitabine and radiotherapy in patients with unresectable pancreatic cancer. Concurrent gemcitabine (400 mg/m2/wk) in six weekly cycles starting on d 1 of radiotherapy (50.4 Gy; 1.8 Gy/fraction/d; 5 d/wk) was prescribed on 22 patients with locally advanced pancreatic cancer. Patients were analyzed with regard to radiological response on computerized tomography, overall survival, and toxicity. Twelve (55%) patients completed the prescription of six gemcitabine cycles and 50.4 Gy radiotherapy; while 10 (45%) received one to five cycles of gemcitabine owing to neutropenia. All patients experienced abdominal discomfort during treatment and three patients required medical intervention. Other toxicities reported were nausea in 13 patients (60%), grade 3 vomiting in 3 (14%). Radiological response evaluations were as follows: complete, 2 (9%); partial, 9 (41%); stable, 7 (32 %); and progressive, 4 (18 %). Median survival was 8.7 mo. Combination of weekly gemcitabine (400 mg/m2) and radiotherapy provided response in 50% of the patients but was associated with severe toxicity resulting in incomplete delivery of the planned chemotherapy. PMID- 17848751 TI - Adrenomedullin expression does not correlate with survival in lung cancer. AB - It is suggested that adrenomedullin (AM) plays a role in lung carcinogenesis although, to confirm this suggestion, further clinical studies are needed to determine its relationship with prognosis in lung cancer. Archived 50 paraffin embedded tumor samples of the lung were retrospectively evaluated for AM expression by immunohistochemistry and analyzed for a possible correlation with patient characteristics and survival. Quantitation of immunoreactivity was accomplished using an immunohistochemical scoring system. The pulmonary resection specimens contained 22 squamous cell carcinomas, 15 adenocarcinomas, and 13 small cell carcinomas. Non-small cell carcinomas of the lung were more likely to express AM than small cell carcinomas of the lung. Ninety-one percent of squamous cell carcinomas and 87% of adenocarcinomas expressed AM at a moderate to strong level and grade2-4 (30-100%), which were significantly higher from the non-neo plastic lung tissue. Twenty-three percent of small cell carcinomas of lung expressed AM. Interestingly, AM immunoreactivity was essentially weak and grade 1 (<%30) in this group. AM expression is upregulated in non-small cell carcinomas of the lung, whereas it is downregulated in small cell carcinomas and non-neo plastic lung tissues. AM expression did not show any correlation with the differentiation of the tumor, the stage of cancer, and the overall survival of patients. These results did not support the role of adrenomedullin as an independent survival factor for lung cancer. However, AM inhibition in conjunction with other anti-angiogenic agents may be useful in the prevention and treatment of malignancies. PMID- 17848752 TI - DPYD*5 gene mutation contributes to the reduced DPYD enzyme activity and chemotherapeutic toxicity of 5-FU: results from genotyping study on 75 gastric carcinoma and colon carcinoma patients. AB - BACKGROUND: Dihydropyrimidine dehydrogenase (DPYD) plays an important role in the metabolism of 5-FU, which can directly influence the pharmacokinetics and toxicity of 5-FU in patients undergoing chemotherapy. However, little is known of the relationship between DPYD gene polymorphism and metabolism and chemotherapeutic toxicity of 5-FU in gastric carcinoma and colon carcinoma. The present genotyping study demonstrated the relationship between DPYD gene polymorphism among 75 gastric carcinoma and colon carcinoma patients and its impact on 5-FU pharmacokinetic and side effect. METHODS: We used a chemotherapy scheme based on 5-FU for the treatment of 75 patients with gastrointestinal carcinoma and detected the serum drug concentration and DPYD gene polymorphism (DPYD*2, *3, *4 *5 *9 *12). RESULTS: We found that there were no DPYD*2, *3, *4, *12 type mutation, in all patients. Of DPYD*9 gene polymorphism loci in 75 patients, 7 were heterozygote and 68 wild type; of DPYD*5 gene polymorphism loci in 75 patients, 11 were mutation and 23 heterozygote and 41 wild type. The elimination rate constant (Ke) value of DPYD*5 mutation group was statistically lower than the wild type (p=0.022). The incidence of middle-severe nausea and vomiting and white blood cell decreases in DPYD*5 gene type ranging from the highest to lowest can be listed as: mutation, heterozygote, wild type (p<0.05). The incidence of middle-severe nausea and vomiting was significantly higher in DPYD*9 heterozygous genotype than in DPYD*9 wild genotype (p<0.05). CONCLUSIONS: DPYD*5 gene mutation contribute to reduced DPYD enzyme activity and 5-FU dysmetabolism, which is associated with the accumulation of 5-FU and the chemotherapeutic toxicity in gastric carcinoma and colon carcinoma. PMID- 17848755 TI - Minimally invasive cardiac surgery in the new millennium. PMID- 17848756 TI - Anaesthesia for MIDCAB / OPCAB. PMID- 17848753 TI - Infusional 5-fluorouracil and cisplatin as first-line chemotherapy in patients with carcinoma of unknown primary site. AB - A combination chemotherapy of 5-fluorouracil (5-FU) and cisplatin (CDDP) has demonstrated activities in various malignancies, including head and neck, lung, esophageal, gastric, and pancreatic cancers. We reviewed our experience of 11 patients diagnosed as carcinoma of unknown primary site (CUPS), who were treated with infusional 5-FU and CDDP between January 1998 and December 2005. The median number of cycles administered was three (range: 1-12). All patients had measurable disease. Six partial responses were obtained (response rate: 54.5%, 95% confidence interval: 23.4-83.3%). The median survival time for all patients was 10 mo (range, 2-37 mo). The median time to disease progression was 3 mo (range, 1-6 mo). This regimen was well tolerated, with grade 3-4 neutropenia (two patients), febrile neutropenia (one patient), grade 3 nausea/vomiting (one patient), and grade 3 stomatitis (two patients). Grade 2 leukoencephalopathy was observed in one patient. No treatment-related death was observed. The combination chemotherapy of infusional 5-FU and CDDP was feasible and tolerated with promising activity for CUPS. PMID- 17848757 TI - Propofol -fentanyl anaesthesia: a comparison with isoflurane-fentanyl anaesthesia in coronary artery bypass graft surgery. AB - The haemodynamic effects of propofol -fentanyl anaesthesia (n=25) were compared with isoflurane-fentanyl anaesthesia (n=25) in patients with normal left ventricular ejection fraction (>45%) undergoing coronary artery bypass graft surgery under cardiopulmonary bypass. In the propofol group (Group P), anaesthesia was induced with midoazolam 2.5 to 5.0 mg, fentanyl 5mg/kg, pancuronium 0.1 mg/kg and propofol 1-2 mg/kg and was maintained with propofol infusion 10 mg/kg/hr till sternotomy, followed by 3 mg/kg/hr till skin closure. In the inhalational group (Group I) anaesthesia was induced with midazolam, fentanyl, pancuronium in the same doses and sleep dose of thiopentone and was maintained with oxygen : nitrous oxide (50:50) and isoflurane (0.5-1%). Additional fentanyl 2.5 microg/kg was given before sternotomy. Haemodynamic measurements were made before induction, after induction, after sternotomy, after heparinisation, after release of aortic cross clamp, post-bypass, post-sternal closure and on arrival in the recovery room. Post-bypass the cardiac index was higher in Group P (2.90+/- 0.76 v/s 2.40 +/- 0.40, p <0.05). Similarly post bypass stroke volume index was higher in Group P (379.32 +/- 6.31 v/s 26.78 +/- 6.24, p<0.05). Patients in Group P were extubated earlier as compared to Group I (379.50 +/- 69 min v/s 453.00 +/- 134 min, p<0.05). This study suggests that propofol may be a suitable adjunct to opioid anaesthesia in patients with normal left ventricular ejection fraction undergoing coronary artery bypass graft surgery. PMID- 17848758 TI - Comparison of the Effects of Sevoflurane and Halothane on Arterial Oxygenation during One Lung Ventilation. AB - We investigated the effect of halothane and sevoflurane on oxygenation during one lung ventilation (OLV) in 24 patients undergoing elective thoracic procedures. After induction with thiopentone, 4-5 mg/kg and morphine 0.1 mg/kg, suxamethonium 2mg/kg was administered to facilitate tracheal intubation with a double lumen tube. Anaesthesia was maintained with 1.5-3% sevolurane (group 1, n = 12) or 1.1.5% halothane (group 2, n = 12) in 02 with N20 (1:1) and pancuronium bromide. Arterial blood gases were recorded before surgery in the lateral position with two lung ventilation (2LV), 10, 20 and 30 minutes after beginning of one lung ventilation. Morphine and endtidal inhalational anaesthetic concentration were titrated to desired anaesthetic depth and haemodynamic variables. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and central venous pressure (CVP) were measured during the study period. In both the groups there was a significant decrease of PaO2 apparent at 10 minutes after initiation of OLV. Thereafter PaO2 remained stable throughout the study period in both the groups. It is concluded that oxygenation did not differ significantly with either sevoflurane or halothane during OLV. It is also concluded that decrease in oxygenation with OLV is complete by 10 minutes of its initiation. PMID- 17848759 TI - High Thoracic Epidural Anaesthesia and Post Operative Analgesia for Fast Tracking Patients undergoing CABG: Our Initial Experience. AB - This prospective study was carried out is 250 patients undergoing CABG. The aim of this study was to assess the effects of high thoracic epidural anaesthesia during CABG, along with modified general anaesthsia; facilitate early extubation and fast tracking post operatively; evaluate effect on post-operative analgesia and discuss difficulties in patient selection for high thoracic epidural catheterization. 250 patients undergoing CABG over a period of nine months were included in this study. Patients with age >64 yrs, weight < 50 kg, EF < 50%, redo surgery, recent MI, receiving aspirin or ticlopidine or heparin were excluded from the study. A thoracic epidural catheter was inserted evening before surgery at T1-2 or T2-3 interspace. A total of 75 patients (30%) were found suitable to be included in this study. On table extubation or early extubation (within 3 hours) was achieved in 85% of cases. Post operative infusion of 0.1% Bupivacaine and 2 microg/ml Fentanyl was given epidurally through a PCA system for analgesia for 48-72 yrs. High thoracic epidural anaesthesia and modified GA regimen were helpful in fast tracking and early extubation of patients. Over 90% patients were discharged on day 5, from the hospital. All these patients experienced significantly less pain and discomfort following CABG. The procedural difficulties for inserting high thoracic epidural catheter were overcome with increasing experience. PMID- 17848760 TI - A comparison of esmolol and diltiazem for heart rate control during coronary revascularisation on beating heart. AB - This prospective study compared control of heart rate and haemodynamics during coronary artery revascularization without cardiopulmonary bypass using either esmolol or diltiazem. Sixty adult patients with one or two vessel coronary artery disease, were randomly divided into 2 groups. Group A (n=30) received a 50 microg/kg/ loading dose of esmolol followed by a 100 microg/kg/hr infusion, for control of heart rate during surgical anastomosis of the coronary vessel. Group-B (n=30) received 0.15 mg/kg of diltiazem as a loading dose followed by a 5 mg/hr infusion for heart rate control, during the anastomosis. It was seen that heart rate control was better in group A, 51.4 +/- 1.3 beats/min, (p <0.01) than in group B, 69.6 +/- 3.0 beats/min (p <0.05), as compared to baseline values of 80.6 +/- 12.1 beats/min in group A and 82.4 +/- 10.6 beats/min in group B respectively. Systemic vascular resistance and pulmonary artery wedge pressure were unchanged in group A but mean pulmonary artery pressure and pulmonary vascular resistance were significantly raised. Group B patients had decreased systemic vascular resistance, mean pulmonary artery pressure and pulmonary artery wedge pressure, and reduced right ventricular stroke work index at the time of distal coronary anastomosis. We concluded that although esmolol provided dramatically slower heart rates, during surgery, the resulting elevations in mean pulmonary artery pressure and pulmonary vascular resistance would require caution if used in patients with underlying right ventricular dysfunction from ischaemia or infarction. Diltiazem by virtue of its effects on systemic vascular resistance, cardiac output, and lowering of mean arterial pressure may be a better choice in hypertensive patients. PMID- 17848761 TI - An Unusual Complication during Lobectomy- The Usefulness of Fibreoptic Bronchoscopy. AB - We describe a case of left lower lobectomy which had to be converted into a left pneumonectomy due to inadvertent resection of left upper lobe bronchus. This was proved by the use of fibreoptic examination of the remaining bronchus and by examination of the resected specimen. PMID- 17848763 TI - Education and training in cardiothoracic anaesthsia. PMID- 17848762 TI - Anaesthesia for CABG Surgery in Patients with Obstructive Sleep Apnoea. PMID- 17848764 TI - Effects of cardiopulmonary bypass on thyroid function. AB - Alterations in serum concentration of thyroid hormones occur even in euthyroid patients undergoing cardiopulmonary bypass. The purpose of our prospective study was to define the effects of cardiopulmonary bypass on thyroid hormones. Twenty euthyroid patients for mitral valve replacement were included in this study. Heparinised arterial sample for thyroid function tests were obtained before cardiopulmonary bypass (CPB), 30 and 60 minutes after initiation of CPB, immediate post-CPB and 24 hours after termination of CPB. T3, T4 and thyroid stimulating hormone (TSH) were estimated using radioimmunoassay method. There was more than 50% decrease in T3 levels after initiation of CPB and it remained persistently below the physiological range until 24 hours after termination of CPB. T4 and TSH remained within normal limits throughout the study period. These results indicate that CPB simulates the euthyroid sick syndrome as seen in critically ill and burn patients. Whether routine administration of intravenous tri-iodo thyronine is beneficial in the prevention of low cardiac output syndrome seen after CPB remains to be elucidated in future. PMID- 17848765 TI - Biochemical Markers of Myocardial Injury during Coronary Artery Bypass Grafting with and without Cardiopulmonary Bypass. AB - Minimally invasive cardiac surgical techniques have been applied recently in the management of variety of cardiac lesions. Between December 1998 and February 1999, fifty patients underwent coronary artery bypass grafting (CABG) under two different techniques. In group A (twenty five patients), CABG was done under cardiopulmonary bypass (CPB) and in group B (twenty three patients), CABG was performed on a 'beating heart' without CPB. Serum concentration of cardiac specific enzymes CPZ-MB and Troponin-T were estimated in all the patients from pre-induction period to 72 hours after the bypass graft. Group A patients exhibited a significant (P<0.05) elevation in the CPK-MB and Troponin-T level as compared to group B. Our results show that the extent of myocardial damage following CABG is significantly less when the procedure is done on a 'beating heart'. PMID- 17848766 TI - Efficacy of reiki on patients undergoing coronary artery bypass graft surgery. AB - Reiki was administered to 50 patients out of 100 patients with normal left ventricular function scheduled for elective coronary artery bypass grafting. Blood components and inflammatory markers were estimated at various time points. Haemodynamic parameters, psychological analysis, intensive care unit stay,incidence of infection, chest tube drainage and mortality were recorded. Haemodynamic parameters and use of blood components were similar in both groups. Interleukin-6 were significantly lower in the preoperative period in the Reiki group, but showed similar trends in both the groups in the post-operative period. The psychological analysis assessed by World Health Organisation quality of life and General Health Questionnaire revealed that social relationships improve once patient is in his own surroundings and with his own people in both the groups. Psychological domain showed significant difference, six day after surgery in the Reiki group. This study concludes that Reiki is a time consuming process with no significant clinical benefit. PMID- 17848767 TI - Acute Normovolaemic Haemodilution and Cardiac Surgery - current opinion and controversies. PMID- 17848768 TI - Inadvertent cannulation of the left internal thoracic vein during central vein catheter insertion. AB - The left internal thoracic vein was accidentally cannulated during an attempt to establish central vein catheterization through left internal jugular vein. The surgeon found this during left internal mammary artery dissection and it needed to be repositioned. PMID- 17848769 TI - Anaesthetic management of a patient undergoing reoperation for pathway obstruction after fontan operation. AB - Since 1968, the Fontan operation, or its various modifications, have provided a functional correction in an increasingly complex spectrum of congenital heart malformations.1.2 These procedures have gained wide acceptance because of very good intermediate and longterm results2. However, as survival increases, follow up of these patients has shown more prevalent reoperations for obstruction of the surgically created corrective pathway.3 perioperative management of these patients requires an understanding of the unique anatomic and physiologic changes occurring in this condition. In this report, we review our anaesthetic management of a patient who underwent reoperation for thrombotic occlusion of the conduit from a previous Fontan procedure. PMID- 17848770 TI - An Unexpected Fatal Complication Following a Re-do Mitral Valve Replacement. AB - Cardiac surgery involving cardiopulmonary bypass (CPB) is known to be associated with many major complications. A rare complication following a re-do mitral valve replacement (MVR) which turned out to be fatal is discussed. PMID- 17848771 TI - Clustering and embedding using commute times. AB - This paper exploits the properties of the commute time between nodes of a graph for the purposes of clustering and embedding, and explores its applications to image segmentation and multi-body motion tracking. Our starting point is the lazy random walk on the graph, which is determined by the heatkernel of the graph and can be computed from the spectrum of the graph Laplacian. We characterize the random walk using the commute time (i.e. the expected time taken for a random walk to travel between two nodes and return) and show how this quantity may be computed from the Laplacian spectrum using the discrete Green's function. Our motivation is that the commute time can be anticipated to be a more robust measure of the proximity of data than the raw proximity matrix. In this paper, we explore two applications of the commute time. The first is to develop a method for image segmentation using the eigenvector corresponding to the smallest eigenvalue of the commute time matrix. We show that our commute time segmentation method has the property of enhancing the intra-group coherence while weakening inter-group coherence and is superior to the normalized cut. The second application is to develop a robust multi-body motion tracking method using an embedding based on the commute time. Our embedding procedure preserves commute time, and is closely akin to kernel PCA, the Laplacian eigenmap and the diffusion map. We illustrate the results both on synthetic image sequences and real world video sequences, and compare our results with several alternative methods. PMID- 17848772 TI - Hybrid detectors for subpixel targets. AB - Subpixel detection is a challenging problem in hyperspectral imagery analysis. Since the target size is smaller than the size of a pixel, detection algorithms must rely solely on spectral information. A number of different algorithms have been developed over the years to accomplish this task, but most detectors have taken either a purely statistical or a physics-based approach to the problem. We present two new hybrid detectors that take advantage of these approaches by modeling the background using both physics and statistics. Results demonstrate improved performance over the well known AMSD and ACE subpixel algorithms in experiments that include multiple targets, images, and area types--especially when dealing with weak targets in complex backgrounds. PMID- 17848773 TI - Restoring 2D content from distorted documents. AB - This paper presents a framework to restore the 2D content printed on documents in the presence of geometric distortion and non-uniform illumination. Compared with textbased document imaging approaches that correct distortion to a level necessary to obtain sufficiently readable text or to facilitate optical character recognition (OCR), our work targets nontextual documents where the original printed content is desired. To achieve this goal, our framework acquires a 3D scan of the document's surface together with a high-resolution image. Conformal mapping is used to rectify geometric distortion by mapping the 3D surface back to a plane while minimizing angular distortion. This conformal "deskewing" assumes no parametric model of the document's surface and is suitable for arbitrary distortions. Illumination correction is performed by using the 3D shape to distinguish content gradient edges from illumination gradient edges in the high resolution image. Integration is performed using only the content edges to obtain a reflectance image with significantly less illumination artifacts. This approach makes no assumptions about light sources and their positions. The results from the geometric and photometric correction are combined to produce the final output. PMID- 17848774 TI - A practical approach for writer-dependent symbol recognition using a writer independent symbol recognizer. AB - We present a practical technique for using a writer-independent recognition engine to improve the accuracy and speed while reducing the training requirements of a writer-dependent symbol recognizer. Our writer-dependent recognizer uses a set of binary classifiers based on the AdaBoost learning algorithm, one for each possible pairwise symbol comparison. Each classifier consists of a set of weak learners, one of which is based on a writer-independent handwriting recognizer. During online recognition, we also use the n-best list of the writer-independent recognizer to prune the set of possible symbols and thus reduce the number of required binary classifications. In this paper, we describe the geometric and statistical features used in our recognizer and our all-pairs classification algorithm. We also present the results of experiments that quantify the effect incorporating a writer-independent recognition engine into a writer-dependent recognizer has on accuracy, speed, and user training time. PMID- 17848775 TI - An efficient multimodal 2D-3D hybrid approach to automatic face recognition. AB - We present a fully automatic face recognition algorithm and demonstrate its performance on the FRGC v2.0 data. Our algorithm is multimodal (2D and 3D) and performs hybrid (feature-based and holistic) matching in order to achieve efficiency and robustness to facial expressions. The pose of a 3D face along with its texture is automatically corrected using a novel approach based on a single automatically detected point and the Hotelling transform. A novel 3D Spherical Face Representation (SFR) is used in conjunction with the SIFT descriptor to form a rejection classifier which quickly eliminates a large number of candidate faces at an early stage for efficient recognition in case of large galleries. The remaining faces are then verified using a novel region-based matching approach which is robust to facial expressions. This approach automatically segments the eyes-forehead and the nose regions, which are relatively less sensitive to expressions, and matches them separately using a modified ICP algorithm. The results of all the matching engines are fused at the metric level to achieve higher accuracy. We use the FRGC benchmark to compare our results to other algorithms which used the same database. Our multimodal hybrid algorithm performed better than others by achieving 99.74% and 98.31% verification rates at 0.001 FAR and identification rates of 99.02% and 95.37% for probes with neutral and non-neutral expression respectively. PMID- 17848776 TI - Weighted graph cuts without eigenvectors a multilevel approach. AB - A variety of clustering algorithms have recently been proposed to handle data that is not linearly separable; spectral clustering and kernel k-means are two of the main methods. In this paper, we discuss an equivalence between the objective functions used in these seemingly different methods--in particular, a general weighted kernel k-means objective is mathematically equivalent to a weighted graph clustering objective. We exploit this equivalence to develop a fast, high quality multilevel algorithm that directly optimizes various weighted graph clustering objectives, such as the popular ratio cut, normalized cut, and ratio association criteria. This eliminates the need for any eigenvector computation for graph clustering problems, which can be prohibitive for very large graphs. Previous multilevel graph partitioning methods, such as Metis, have suffered from the restriction of equal-sized clusters; our multilevel algorithm removes this restriction by using kernel k-means to optimize weighted graph cuts. Experimental results show that our multilevel algorithm outperforms a state-of-the-art spectral clustering algorithm in terms of speed, memory usage, and quality. We demonstrate that our algorithm is applicable to large-scale clustering tasks such as image segmentation, social network analysis and gene network analysis. PMID- 17848777 TI - Classification and recognition of dynamical models: the role of phase, independent components, kernels and optimal transport. AB - We address the problem of performing decision tasks, and in particular classification and recognition, in the space of dynamical models in order to compare time series of data. Motivated by the application of recognition of human motion in image sequences, we consider a class of models that include linear dynamics, both stable and marginally stable (periodic), both minimum and non minimum phase, driven by non-Gaussian processes. This requires extending existing learning and system identification algorithms to handle periodic modes and nonminimum phase behavior, while taking into account higher-order statistics of the data. Once a model is identified, we define a kernel-based cord distance between models that includes their dynamics, their initial conditions as well as input distribution. This is made possible by a novel kernel defined between two arbitrary (non-Gaussian) distributions, which is computed by efficiently solving an optimal transport problem. We validate our choice of models, inference algorithm, and distance on the tasks of human motion synthesis (sample paths of the learned models), and recognition (nearest-neighbor classification in the computed distance). However, our work can be applied more broadly where one needs to compare historical data while taking into account periodic trends, non-minimum phase behavior, and non-Gaussian input distributions. PMID- 17848778 TI - Registration of challenging image pairs: initialization, estimation, and decision. AB - Our goal is an automated 2D-image-pair registration algorithm capable of aligning images taken of a wide variety of natural and man-made scenes as well as many medical images. The algorithm should handle low overlap, substantial orientation and scale differences, large illumination variations, and physical changes in the scene. An important component of this is the ability to automatically reject pairs that have no overlap or have too many differences to be aligned well. We propose a complete algorithm, including techniques for initialization, for estimating transformation parameters, and for automatically deciding if an estimate is correct. Keypoints extracted and matched between images are used to generate initial similarity transform estimates, each accurate over a small region. These initial estimates are rank-ordered and tested individually in succession. Each estimate is refined using the Dual-Bootstrap ICP algorithm, driven by matching of multiscale features. A three-part decision criteria, combining measurements of alignment accuracy, stability in the estimate, and consistency in the constraints, determines whether the refined transformation estimate is accepted as correct. Experimental results on a data set of 22 challenging image pairs show that the algorithm effectively aligns 19 of the 22 pairs and rejects 99.8% of the misalignments that occur when all possible pairs are tried. The algorithm substantially out-performs algorithms based on keypoint matching alone. PMID- 17848779 TI - Methods for fine registration of cadastre graphs to images. AB - We propose two algorithms to match edges in a geometrically-imprecise graph to geometrically-precise strong boundaries in an image, where the graph is meant to give an a priori partition of the image into objects. This can be used to partition an image into objects described by imprecise external data, and thus to simplify the segmentation problem. We apply them to the problem of registering cadastre data to georeferenced aerial images, thus correcting the lack of geometrical detail of the cadastre data, and the fact that cadastre data gives information of a different nature than that found in images (fiscal information as opposed to actual land use). PMID- 17848780 TI - Shape estimation using polarization and shading from two views. AB - This paper presents a novel method for 3D surface reconstruction that uses polarization and shading information from two views. The method relies on polarization data acquired using a standard digital camera and a linear polarizer. Fresnel theory is used to process the raw images and to obtain initial estimates of surface normals, assuming that the reflection type is diffuse. Based on this idea, the paper presents two novel contributions to the problem of surface reconstruction. The first is a technique to enhance the surface normal estimates by incorporating shading information into the method. This is done using robust statistics to estimate how the measured pixel brightnesses depend on the surface orientation. This gives an estimate of the object material reflectance function, which is used to refine the estimates of the surface normals. The second contribution is to use the refined estimates to establish correspondence between two views of an object. To do this, a set of patches are extracted from each view and are aligned by minimizing an energy functional based on the surface normal estimates and local topographic properties. The optimum alignment parameters for different patch pairs are then used to establish stereo correspondence. This process results in an unambiguous field of surface normals, which can be integrated to recover the surface depth. Our technique is most suited to smooth, non-metallic surfaces. It complements existing stereo algorithms since it does not require salient surface features to obtain correspondences. An extensive set of experiments, yielding reconstructed objects and reflectance functions, are presented and compared to ground truth. PMID- 17848781 TI - Shape estimation of transparent objects by using inverse polarization ray tracing. AB - Few methods have been proposed to measure three-dimensional shapes of transparent objects such as those made of glass and acrylic. In this paper, we propose a novel method for estimating the surface shapes of transparent objects by analyzing the polarization state of the light. Existing methods do not fully consider the reflection, refraction, and transmission of the light occurring inside a transparent object. We employ a polarization raytracing method to compute both the path of the light and its polarization state. Polarization raytracing is a combination of conventional raytracing, which calculates the trajectory of light rays, and Mueller calculus, which calculates the polarization state of the light. First, we set an initial value of the shape of the transparent object. Then, by changing the shape, the method minimizes the difference between the input polarization data and the rendered polarization data calculated by polarization raytracing. Finally, after the iterative computation is converged, the shape of the object is obtained. We also evaluate the method by measuring some real transparent objects. PMID- 17848782 TI - BM3 E: discriminative density propagation for visual tracking. AB - We introduce BM3 E, a Conditional Bayesian Mixture of Experts Markov Model, for consistent probabilistic estimates in discriminative visual tracking. The model applies to problems of temporal and uncertain inference and represents the unexplored bottom-up counterpart of pervasive generative models estimated with Kalman filtering or particle filtering. Instead of inverting a non-linear generative observation model at run-time, we learn to cooperatively predict complex state distributions directly from descriptors that encode image observations - typically bag-of-feature global image histograms or descriptors computed over regular spatial grids. These are integrated in a conditional graphical model in order to enforce temporal smoothness constraints and allow a principled management of uncertainty. The algorithms combine sparsity, mixture modeling, and non-linear dimensionality reduction for efficient computation in high-dimensional continuous state spaces. The combined system automatically self initializes and recovers from failure. The research has three contributions: (1) We establish the density propagation rules for discriminative inference in continuous, temporal chain models; (2) We propose flexible supervised and unsupervised algorithms for learning feedforward, multivalued contextual mappings (multimodal state distributions) based on compact, conditional Bayesian mixture of experts models; (3) We validate the framework empirically for the reconstruction of 3d human motion in monocular video sequences. Our tests on both real and motion capture-based sequences show significant performance gains with respect to competing nearest-neighbor, regression, and structured prediction methods. PMID- 17848783 TI - Space-time behavior-based correlation-Or-how to tell if two underlying motion fields are similar without computing them? AB - We introduce a behavior-based similarity measure which tells us whether two different space-time intensity patterns of two different video segments could have resulted from a similar underlying motion field. This is done directly from the intensity information, without explicitly computing the underlying motions. Such a measure allows us to detect similarity between video segments of differently dressed people performing the same type of activity. It requires no foreground/background segmentation, no prior learning of activities, and no motion estimation or tracking. Using this behavior-based similarity measure, we extend the notion of 2-dimensional image correlation into the 3-dimensional space time volume, thus allowing to correlate dynamic behaviors and actions. Small space-time video segments (small video clips) are "correlated" against entire video sequences in all three dimensions (x,y, and t). Peak correlation values correspond to video locations with similar dynamic behaviors. Our approach can detect very complex behaviors in video sequences (e.g., ballet movements, pool dives, running water), even when multiple complex activities occur simultaneously within the field-of-view of the camera. We further show its robustness to small changes in scale and orientation of the correlated behavior. PMID- 17848784 TI - Image analysis using hahn moments. AB - This paper shows how Hahn moments provide a unified understanding of the recently introduced Chebyshev and Krawtchouk moments. The two latter moments can be obtained as particular cases of Hahn moments with the appropriate parameter settings, and this fact implies that Hahn moments encompass all their properties. The aim of this paper is twofold: 1) To show how Hahn moments, as a generalization of Chebyshev and Krawtchouk moments, can be used for global and local feature extraction, and 2) to show how Hahn moments can be incorporated into the framework of normalized convolution to analyze local structures of irregularly sampled signals. PMID- 17848785 TI - Renewable fluid dynamic energy derived from aquatic animal locomotion. AB - Aquatic animals swimming in isolation and in groups are known to extract energy from the vortices in environmental flows, significantly reducing muscle activity required for locomotion. A model for the vortex dynamics associated with this phenomenon is developed, showing that the energy extraction mechanism can be described by simple criteria governing the kinematics of the vortices relative to the body in the flow. In this way, we need not make direct appeal to the fluid dynamics, which can be more difficult to evaluate than the kinematics. Examples of these principles as exhibited in swimming fish and existing energy conversion devices are described. A benefit of the developed framework is that the potentially infinite-dimensional parameter space of the fluid-structure interaction is reduced to a maximum of eight combinations of three parameters. The model may potentially aid in the design and evaluation of unsteady aero- and hydrodynamic energy conversion systems that surpass the Betz efficiency limit of steady fluid dynamic energy conversion systems. PMID- 17848786 TI - Jumping robots: a biomimetic solution to locomotion across rough terrain. AB - This paper introduces jumping robots as a means to traverse rough terrain; such terrain can pose problems for traditional wheeled, tracked and legged designs. The diversity of jumping mechanisms found in nature is explored to support the theory that jumping is a desirable ability for a robot locomotion system to incorporate, and then the size-related constraints are determined from first principles. A series of existing jumping robots are presented and their performance summarized. The authors present two new biologically inspired jumping robots, Jollbot and Glumper, both of which incorporate additional locomotion techniques of rolling and gliding respectively. Jollbot consists of metal hoop springs forming a 300 mm diameter sphere, and when jumping it raises its centre of gravity by 0.22 m and clears a height of 0.18 m. Glumper is of octahedral shape, with four 'legs' that each comprise two 500 mm lengths of CFRP tube articulating around torsion spring 'knees'. It is able to raise its centre of gravity by 1.60 m and clears a height of 1.17 m. The jumping performance of the jumping robot designs presented is discussed and compared against some specialized jumping animals. Specific power output is thought to be the performance-limiting factor for a jumping robot, which requires the maximization of the amount of energy that can be stored together with a minimization of mass. It is demonstrated that this can be achieved through optimization and careful materials selection. PMID- 17848787 TI - Artificial gills for robots: MFC behaviour in water. AB - This paper reports on the first stage in developing microbial fuel cells (MFCs) which can operate underwater by utilizing dissolved oxygen. In this context, the cathodic half-cell is likened to an artificial gill. Such an underwater power generator has obvious potential for autonomous underwater robots. The electrical power from these devices increased proportionately with water flow rate, temperature and salinity. The current output at ambient temperature (null condition) was 32 microA and this increased by 200% (approximately 100 microA) as a result of a corresponding temperature increase (DeltaT) of 52 degrees C. Similarly, the effect of increasing the water flow rate resulted in an increase in the MFC output ranging from 135% to 150%. Furthermore, the same positive effect was recorded when artificial seawater was used instead, in which case the increase in the MFC current output was >100% (from 32 to 65 microA). There was a distinct difference in the MFC performance when operated under low turbulent as opposed to high turbulent flow rates. These findings can be advantageous in the design of underwater autonomous robots. PMID- 17848788 TI - A model of modes of attention and inattention for artificial perception. AB - This paper considers several aspects of natural visual attention and its link to wider notions of awareness, natural and artificial, in the context of foveated vision. It builds on a theory of abductive perception; a formal definition for an artificial or robot perceptual system, using objects represented as feature clouds. It proposes a broad, but unifying approach to several aspects of visual attention in the light of this, including autonomic eye gaze movements, aspects of secondary and covert attention, and exogenous (sense driven) and endogenous (task driven) attention. Modes of attentional lapse, commonly referred to as inattentional blindness and change blindness, are also discussed in the context of the model presented. PMID- 17848789 TI - Systematic fabrication of nano-carbonated hydroxyapatite/collagen composites for biomimetic bone grafts. AB - A novel biomimetic self-assembly method was designed to create nano-carbonated hydroxyapatite/collagen (nCHAC) composites by means of incorporating various collagen and carbonate concentrations using solutions such as CaCl(2), H(3)PO(4), and Na(2)CO(3). At a given range of collagen and carbonate content, the nanosized inorganic phase of the newly synthesized material has a low degree of crystallinity which resembles that of natural bone. By manipulating the concentrations of collagen and carbonates, various morphologies of the nCHAC can be obtained. The crystal size of nCHAC is dependent on the concentration of carbonate and collagen present in the composites. For instance, higher collagen concentration results in smaller crystal nCHAC crystal size. Conversely, the higher the carbonate content, the smaller are the crystal size and the collagen fibril assembly. As the carbonate content increased, the plate-like crystals first became needle-like structures, subsequently short needle-like crystals and eventually became spherical particles. From this study, our method showcased the flexibility of fabricating various types of nCHAC composites which can be designed for different bone applications. PMID- 17848790 TI - A novel distributed swarm control strategy based on coupled signal oscillators. AB - The miniaturization of microrobots is accompanied by limitations of signaling, sensing and agility. Control of a swarm of simple microrobots has to cope with such constraints in a way which still guarantees the accomplishment of a task. A recently proposed communication method, which is based on the coupling of signal oscillators of individual agents [13], may provide a basis for a distributed control of a simulated swarm of simple microrobots (similar to I-Swarm microrobots) engaged in a cleaning scenario. This self-organized communication method was biologically inspired from males of chorusing insects which are known for the rapid synchronization of their acoustic signals in a chorus. Signal oscillator properties were used to generate waves of synchronized signaling (s waves) among a swarm of agents. In a simulation of a cleaning scenario, agents on the dump initiated concentrically spreading s-waves by shortening their intrinsic signal period. Dirt-carrying agents localized the dump by heading against the wave front. After optimization of certain control parameters the properties of this distributed control strategy were investigated in different variants of a cleaning scenario. These include a second dump, obstacles, different agent densities, agent drop-out and a second signal oscillator. PMID- 17848791 TI - Histamine and the regulation of body weight. AB - Energy intake and expenditure is regulated by a complex interplay between peripheral and central factors. An exhaustive list of peptides and neurotransmitters taking part in this complex regulation of body weight exists. Among these is histamine, which acts as a central neurotransmitter. In the present article we review current evidence pointing at an important role of histamine in the regulation of appetite and metabolism. Studies using both knockout mouse models as well as pharmacological studies have revealed that histamine acts as an anorexigenic agent via stimulation of histamine H(1) receptors. One effect of histamine in the regulation of appetite is to act as a mediator of the inhibitory effect of leptin on appetite. It seems that histamine may attenuate and delay the development of leptin resistance in high-fat-diet induced obesity. Furthermore, histamine may also act to accelerate lipolysis. Based on the current evidence of the involvement of histamine in the regulation of body weight, the histaminergic system is an obvious target for the development of pharmacological agents to control obesity. At present, H(3) receptor antagonists that stimulate the histaminergic system may be the most promising histaminergic drugs for antiobesity therapy. PMID- 17848792 TI - Decision making for solitary vestibular schwannoma and contralateral Meniere's disease. AB - The existence of dual inner ear pathology such as unilateral Meniere's disease (MD) with a contralateral vestibular schwannoma (VS) is very rare, but provides the otologist with a significant management dilemma. In this study, we present 5 cases of unilateral disabling MD with a contralateral VS in the better hearing ear. Conservative management of the VS is mandated unless there are impending complications, with management directed toward controlling the vertigo attributed to MD. If and when the VS requires intervention, or the hearing in that ear deteriorates to unserviceable levels, cochlear implant of the ear affected by MD prior to addressing the VS provides optimal management. PMID- 17848793 TI - Mild cognitive impairment in general practice: age-specific prevalence and correlate results from the German study on ageing, cognition and dementia in primary care patients (AgeCoDe). AB - BACKGROUND: Although mild cognitive impairment (MCI) represents a high-risk factor for developing dementia, little is known about the prevalence of MCI among patients of general practitioners (GPs). AIMS: Estimation of age-specific prevalence for original and modified concepts of MCI and their association with sociodemographic, medical and genetic (apoE epsilon4 genotype) factors among patients of GPs. METHODS: A GP practice sample of 3,327 individuals aged 75+ was assessed by structured clinical interviews. RESULTS: Prevalence was 15.4% (95% CI = 14.1-16.6) for original and 25.2% (95% CI = 23.7-26.7) for modified MCI. Rates increased significantly with older age. Positive associations were found for apoE epsilon4 allele, vascular diseases and depressive symptoms. CONCLUSION: MCI is frequent in elderly patients of GPs. GPs have a key position in secondary prevention and care of incipient cognitive deterioration up to the diagnosis of dementia. PMID- 17848794 TI - Silent celiac disease is frequent in the siblings of newly diagnosed celiac patients. AB - BACKGROUND/AIMS: Celiac disease is caused by environmental and genetic factors, and the relatives of celiac patients are at higher risk of developing celiac disease than the general population. This prospective study evaluates the prevalence of celiac disease in the asymptomatic siblings of celiac patients. METHODS: Forty-eight siblings (22 males; mean age 13 years) of 39 celiac children (20 males; mean age 4 years), and 120 siblings (55 males; mean age 33 years) of 55 adult celiac patients (12 males; mean age 31 years) were serologically screened for celiac disease. Positive cases were considered for endoscopic duodenal biopsies. RESULTS: Forty of the 168 asymptomatic siblings (23.8%) were affected by celiac disease. There were no differences between the index cases with and without affected siblings in terms of age at diagnosis, symptoms at onset, order of birth, associated disorders or other affected relatives. The male siblings of pediatric patients were affected in 40.9% of cases and female siblings in 26.9%; the corresponding figures for adults were 16.4 and 23.1%. CONCLUSIONS: Silent celiac disease is 24-48 times more frequent in the siblings of celiac patients than in the general population. No predictive factors for sibling involvement were found. Adult females seem to tolerate gluten less than adult males. PMID- 17848795 TI - [When therapy cannot alter prognosis...]. PMID- 17848796 TI - Does aerobic training enhance effects of spa therapy in back pain patients? A randomized, controlled clinical trial. AB - OBJECTIVES: The aim of the present study was to evaluate the effects of 3 weeks of individualized aerobic exercise training combined with conventional spa therapy on patients' assessment of chronic pain and quality of life. PATIENTS AND METHODS: 44 patients of either sex and advanced age (50-70 years) with chronic pain underwent an inpatient spa therapy in Bad Tatzmannsdorf, Austria. Participants were randomized into 2 groups, a control group receiving spa therapy alone, and a training group carrying out an additional aerobic training. Every participant performed an exhaustive bicycle exercise test at the beginning of the study. Subsequently, participants of the training group performed individualized training programs, controlled and documented by ambulatory heart rate monitors. At the beginning and the end of the study the following outcome measures were assessed by use of questionnaires: positive and negative mood, general depression, health satisfaction, general pain, exhaustion, abdominal complaints, and cardiac pain. The results of the questionnaires were analyzed by use of a MANOVA to evaluate differences between the two groups. RESULTS: We observed positive effects in all participants and on all parameters investigated after 3 weeks of spa therapy. However, no significant differences could be demonstrated between the two groups (all p > 0.05). CONCLUSION: Individualized aerobic training does not seem to enhance beneficial effects of a 3-week spa therapy on chronic pain and quality of life. PMID- 17848797 TI - [Prescribing practices in the treatment of upper respiratory tract infections in anthroposophic medicine]. AB - BACKGROUND: Upper respiratory tract infections (URTI) are among the leading reasons for doctor consultations. This study investigates the prescribing practices of medical doctors specialized in anthroposophic medicine in the treatment of URTI with a special focus on the prescription of antibiotics, complications, recurrence rates and costs. MATERIALS AND METHODS: Starting in May 2004 all prescriptions within a 1-year period by 35 primary care practitioners in Germany were analysed. Data were extracted from practice software with special interfaces with additional linking of medications and diagnoses by practitioners. RESULTS: 21,818 prescriptions for 12,081 patients (73.7%children) with 19,050 cases of URTI were analysed. The most common diagnosis was common cold (63.3%), followed by acute tonsillitis (12.9%). 63.0% were treated purely with complementary medicine. Antibiotics were given in 6.3% of cases (minimum: common cold 1.9%, maximum: tonsillitis 24.3%). Predictive factors for antibiotic prescribing were the diagnoses tonsillitis (odds ratio [OR]: 6.7; 95% confidence interval [CI]:4.5-9.9) and sinusitis (OR: 1.9; 95% CI: 1.1-3.1), concomitant disease (OR: 1.2; 95% CI: 1.0-1.4), complications (OR: 7.2; 95% CI:5.5-9.4) and the specialty paediatrics (OR: 2.1; 95% CI: 1.7-2.6). In cases that were initially treated with only complementary medicine, antibiotics were eventually prescribed in 0.7%. Overall complication rates were 2.9% and follow-up visits occurred in 6.3%. Patients had an average of 2.4 URTI/year (adults 1.7,children 2.7). Treatment costs did not differ between complementary care and antibiotics. CONCLUSION: Prescription practices in the treatment of URTI by anthroposophic practitioners were documented through the processing of routine medical data with minimal additional data. The therapy was found to be in accordance with the guidelines, however, the prescription rate for antibiotics was well below the German average. PMID- 17848798 TI - Phantasy therapy: statistical evaluation of a new approach to group psychotherapy for stationary and ambulatory psychotic patients. AB - BACKGROUND: Since 1995 we have developed a depth-psychological, experience- and expression-oriented approach to group therapy for psychotic patients--"Phantasy Therapy"--complementary to the main-stream emphasis upon behavioural, learn- and goal-oriented methods. AIMS: A group psychotherapy for acute and remitting patients suffering from psychosis or schizophrenia is statistically evaluated under treatment-as-usual in a public psychiatric clinic. METHODS: Phantasy Therapy is compared to an alternative treatment (art therapy = AT) and a placebo group (PG; weekly ward gatherings) via cognitive testing before and after each session. RESULTS: (1) Improvement of cognitive deficits over the first 4 sessions: session 1 (effect size d = 0 between all 3 groups) versus session 4 (d = 0.2 and 0.4 of Phantasy Therapy over AT and PG, respectively). Averaged over the first 4 sessions, the cognitive test showed tendential improvements for Phantasy Therapy and AT compared to PG. (2) Self-rating (sum of 4 item scores) averaged over the first 4 sessions showed a small effect. Patients judged themselves more improved after Phantasy Therapy compared to AT (d = 0.2) or PG (d = 0.3); tendential d (0.1) of AT over PG. (3) Psychosocial communication skills considerably improved during Phantasy Therapy, slightly worsened during AT, and remained relatively unchanged during PG. The effect sizes of Phantasy Therapy for values averaged over the first 4 sessions was 0.6 compared to AT and 0.4 compared to PG. CONCLUSIONS: Phantasy Therapy is better than PG and at least as good as AT. These results should be hardened by further studies. PMID- 17848799 TI - A bio-psycho-socio-molecular approach to pain and stress management. AB - Stress and trauma are interconnected with the experience of pain. This connection is due to a physiological coupling of underlying molecular autoregulatory mechanisms, as well as phenomenological similarities. Nonpharmaceutical therapeutic approaches such as the relaxation response, a process that supports physiological stress reduction and decreases the negative mental and physical effects of stress, also facilitate pain relief, again demonstrating physiological commonalities. These behavioral approaches have a critical impact on molecular patterns of autoregulation, leading to the assumption of a bio-psycho-socio molecular model of autoregulation, including stress and pain. Thus, molecules and behavior may be seen as two sides of the same problem in pain and stress relief. PMID- 17848800 TI - [Fasting as part of a naturopathic treatment approach for polymyalgia rheumatica]. AB - A 67-year-old woman with proven diagnosis of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) was admitted to stationary treatment twice to receive a complex therapy with methods of natural medicine comprising fasting as its main treatment element. Both times, a discrepancy between the course of markers of the acute phase on the one hand, and subjective as well as objective clinical outcome on the other hand could be observed. This may point to special conditions of this chronic inflammatory disease as compared to e.g.rheumatoid arthritis, but also to specific problems in assessing possible effects of the treatments chosen, particularly fasting therapy, as compared to effects of conventional therapies. PMID- 17848801 TI - [The meaning of wholeness in medical philosophy]. AB - Organisms are "wholes" insofar as togetherness with others is essential for their development and identity. The female egg is the first and original environment into which a human individual develops. The three main spheres of holistic togetherness in which man further becomes himself in joining the world are (1) psychic togetherness of the organs, (2) social togetherness with fellow human beings and (3) natural togetherness or connaturality, in the whole of nature. Health and disease can originate on any of these levels. On the first one psychosomatic experiences tend to be confirmed by recent results of psychoneuroimmunology. On the second level health or pathogenicity of private or professional social environments tend to be much better known in social medicine (public health) than in medical practice. Corresponding research on the third level is much less advanced. Medical care can be secondary to cultivating social and natural togetherness. PMID- 17848803 TI - Homeopathy and placebo--synonym, similar or different? PMID- 17848804 TI - Effect of ciclesonide treatment on allergen-induced changes in T cell regulation in asthma. AB - BACKGROUND: The allergen-induced release of CCL17/thymus and activation-regulated chemokine (TARC) may be crucial in asthmatic airway inflammation by recruitment of Th2 cells. In addition, it might lead to aberrant Th2 cell activity through impairment of beta2-adrenergic receptor (beta2-AR) control. We questioned how chemokine patterns change upon allergen challenge and whether treatment with the inhaled steroid ciclesonide can reduce chemokine release and subsequently prevent allergen-induced changes in Th2 cell regulation and migration. METHODS: Asthma patients were double-blindly treated with placebo or 80 microg ciclesonide for 7 days. We studied allergen-induced changes in sputum chemokines, migration of peripheral blood T cells and control of beta2-agonist fenoterol over T cell migration and alpha-CD3/alpha-CD28-induced cytokine production. RESULTS: Treatment with 80 microg ciclesonide significantly diminished the late asthmatic response. The late asthmatic response was associated with increased sputum levels of CCL17 and CCL4 (but none of the other chemokines measured) and loss of beta2 AR control over T cell migration and Th2-type cytokine production. Although ciclesonide treatment did not prevent chemokine release nor altered beta2-AR function in circulating T cells, it exerted an inhibitory effect on TARC-induced T cell migration and alpha-CD3/alpha-CD28-induced cytokine production. CONCLUSION: Our data support the hypothesis that CCL17 is involved in allergen induced dysregulation of Th2 cell migration and cytokine production. Ciclesonide treatment inhibits T cell migration and cytokine production upon allergen inhalation, which is regulated independently from reducing CCL17 release, but may contribute to beneficial effects of ciclesonide on Th2-mediated airway inflammation. PMID- 17848805 TI - Year-to-year variation in release of Bet v 1 allergen from birch pollen: evidence for geographical differences between West and South Germany. AB - BACKGROUND: The release of the aeroallergen Bet v 1 from pollen is a major determinant in the etiology of allergic airway disease due to birch pollen. OBJECTIVE: We determined the release of the major birch pollen allergen Bet v 1 from pollen of birch trees growing in 2 different geographic regions in Germany for 2 consecutive years. METHODS: Catkins were collected during pollination in 2002 and 2003 from 82 healthy trees in South (Munich) and West Germany (North Rhine-Westphalia). The release of Bet v 1 from pollen samples was determined by a Bet v 1-specific ELISA. RESULTS: Pollen from South Germany released about 3 times more Bet v 1 than those from West Germany in both 2002 and 2003 (p = 0.034 and p = 0.007, respectively). This was independent of the number of pollen during the pollen flight season. In 2003, the release of Bet v 1 from pollen was more than 5 times higher than in 2002 in both regions (South Germany 6.1 times, p < 0.001; West Germany 5.4 times, p = 0.003). CONCLUSIONS: Despite large individual differences, there seem to be regional and year-to-year variations in Bet v 1 release from birch pollen. Therefore, the combination of pollen count and release of Bet v 1 from this pollen must be assessed to estimate Bet v 1 exposure reliably. PMID- 17848806 TI - Inhibition of basic secretagogue-induced signaling in mast cells by cell permeable G alpha i-derived peptides. AB - BACKGROUND: Basic secretagogues of connective tissue mast cells act as receptor mimetic agents that trigger mast cells by activating G proteins. This leads to simultaneous propagation of two signaling pathways: one that culminates in exocytosis, while the other involves protein tyrosine phosphorylation and leads to release of arachidonic acid metabolites. We have previously shown that introduction of a peptide that comprises the C-terminal end of G alpha i3 into permeabilized mast cells inhibits basic secretagogue-induced exocytosis [Aridor et al., Science 1993;262:1569-1572]. We investigated whether cell-permeable peptides, composed of the C-terminus of G alpha i3 fused with importation sequences, affect mast cell function. METHODS: Following preincubation with the fused peptides, rat peritoneal mast cells were activated by compound 48/80 and analyzed for histamine and prostaglandin D2 release and protein tyrosine phosphorylations. RESULTS: We demonstrate that out of three importation sequences tested only G alpha i3 peptide fused with the Kaposi fibroblast growth factor importation sequence (ALL1) inhibited release of histamine. ALL1 as well as a cell-permeable peptide that corresponds to G alpha i2 also blocked compound 48/80 stimulated protein tyrosine phosphorylation, though the latter did not block histamine release. ALL1 effect was G protein-specific, as it was incapable of blocking protein tyrosine phosphorylation stimulated by pervanadate. CONCLUSION: ALL1, a transducible G alpha i3-corresponding peptide, blocks the two signaling pathways in mast cells: histamine release and protein tyrosine phosphorylation. Cell permeable peptides that block these two signaling cascades may constitute a novel approach for preventing the onset of the allergic reaction. PMID- 17848807 TI - Dietary supplementation with lactic acid bacteria attenuates the development of atopic-dermatitis-like skin lesions in NC/Nga mice in a strain-dependent manner. AB - BACKGROUND: Dietary supplementation with lactic acid bacteria (LAB) is a potential approach to the prevention and manipulation of allergic diseases such as atopic dermatitis (AD). However, the influence of different bacterial strains and their immunomodulating capacities is still largely unknown. METHODS: AD-like skin lesions were induced by sensitization to and repeated challenges with picrylchloride in the Th2-skewed NC/Nga mouse strain. The effects of LAB supplementation were assessed over time by monitoring clinical scores and plasma IgE levels. In some cases, mast cell infiltration, cutaneous hypersensitivity responses and cytokine mRNA expression in auricles were also examined. Additionally, cytokine production in vitro and cytokine mRNA accumulation in major lymphoid tissues were measured, comparing Lactobacillus paracasei KW3110 with L. rhamnosus GG (LGG). RESULTS: Supplementation with KW3110 significantly reduced the development of AD-like skin lesions, accompanied by less mast cell infiltration and lower plasma IgE levels. KW3110 also suppressed immediate hypersensitivity reactions and IL-4 mRNA expression in the auricles. These preventive effects sustained when supplementation was terminated; moreover, inhibitory effects were also observed even when supplementation was initiated after the onset of symptoms. In accordance with its effects on IL-12 and IL-4 production in vitro, KW3110 prevented the emergence of clinical symptoms more effectively than LGG in vivo. CONCLUSIONS: Supplementation with KW3110 significantly attenuated the onset and exacerbation of AD-like symptoms in NC/Nga mice. The effects were more prominent than those obtained with LGG, suggesting the importance of differences between LAB strains and their immunomodulating capacity. PMID- 17848808 TI - IL-10-inducing adjuvants enhance sublingual immunotherapy efficacy in a murine asthma model. AB - BACKGROUND: IL-10-inducing adjuvants could enhance the efficacy of allergy vaccines in establishing allergen-specific tolerance. The aim of this study was to identify such adjuvants using in vitro cultures of human and murine cells and to evaluate them in a therapeutic murine model of sublingual immunotherapy (SLIT). METHODS: Adjuvants stimulating IL-10 gene expression by human or murine immune cells were tested sublingually in BALB/c mice sensitized to ovalbumin (OVA), assessing the reduction in airway hyperresponsiveness (AHR) by whole-body plethysmography. The induction of regulatory T cells (T(reg)) was evaluated using phenotypic and functional assays. T-cell proliferation in cervical lymph nodes (LNs) was assessed following intravenous transfer of CFSE-labelled OVA-specific T cells and FACS analysis. RESULTS: A combination of 1,25-dihydroxyvitamin D3 plus dexamethasone (VitD3/Dex) as well as Lactobacillus plantarum were found to induce IL-10 production by human and murine dendritic cells (DCs). The former inhibits LPS-induced DC maturation, whereas L. plantarum induces DC maturation. Following stimulation with VitD3/Dex-pretreated DCs, CD4+ naive T cells exhibit a T(reg) profile. In contrast, a Th1/T(reg) pattern of differentiation is observed in the presence of DCs treated with L. plantarum. Both adjuvants significantly enhance SLIT efficacy in mice, in association with either induction of Foxp3+ T(reg) cells (for VitD3/Dex) or proliferation of OVA-specific T cells in cervical LNs (for L. plantarum). CONCLUSIONS: Both VitD3/Dex and L. plantarum polarize naive T cells towards IL-10-expressing T cells, through distinct mechanisms. As adjuvants, they both enhance SLIT efficacy in a murine asthma model. PMID- 17848809 TI - Restenosis following percutaneous renal artery revascularization. AB - BACKGROUND/AIMS: Restenosis following percutaneous transluminal renal angioplasty (PTRA) remains a concern even in the era of adjuvant stenting. The optimal form of therapy, and particularly the role of repeat PTRA in the treatment of recurrent hypertension associated with renal artery restenosis, is largely unknown. The aims of this study were to determine the risk factors for restenosis and to evaluate the blood pressure outcomes of patients who underwent repeat PTRA. METHODS: Clinical and procedural characteristics of 32 patients who developed recurrent hypertension and renal artery restenosis were compared to a control group of patients who maintained renal artery patency and adequate blood pressure control after the first procedure. The groups were matched for sex and initial procedure date. RESULTS: The restenosis group had a mean age of 71 +/- 12 years, a female/male ratio of 24/8, an average blood pressure of 179/87 mm Hg, despite three antihypertensive medications, and a serum creatinine level of 1.5 +/- 0.4 mg/dl. Repeat PTRA performed for clinically significant restenosis was 10.7 +/- 8 months after the first procedure, and 17 of the 32 patients had a measurable blood pressure benefit at last follow-up (177 +/- 119 weeks). The development of restenosis was positively associated with body weight (p = 0.003) and body mass index (p = 0.008), but independent of diabetes mellitus, hyperlipidemia, or statin therapy. Of the 15 patients who failed the second procedure, 4 went on to have third PTRA, none of whom had sustained benefit. CONCLUSIONS: An increased body mass index is associated with restenosis following initial PTRA. Patients with restenosis can be treated successfully with repeat PTRA which provides sustained improvement in blood pressure control in approximately half of these patients. PMID- 17848810 TI - Docetaxel weekly with metastatic breast cancer. PMID- 17848811 TI - Symptom-oriented follow-up of early breast cancer - as good as conventional control and sparing resources. PMID- 17848812 TI - Evaluation and modification of the Tomita score in 217 patients with vertebral metastases. AB - BACKGROUND: The Tomita prognosis score consists of the following 3 parameters: growth behavior, evidence of visceral metastases, and/or evidence of bony metastases. METHODS: 217 consecutive patients, surgically treated for vertebral metastases of different entities, were studied retrospectively. The score according to Tomita was determined. RESULTS: In the study group, the Tomita score showed significant results for the estimation of life expectancy of the different prognostic groups (p < 0.0001), but the analysis showed a low reliability, i.e. correlation between predicted prognosis and real survival. A modified division of the patients based on the total sum of points allowed a significant separation (p < 0.0001) of patients into 2 prognostic groups with a real survival of more or less than 12 months. CONCLUSION: In our study, the original Tomita score was not reliable to predict the life expectancy of cancer patients with spinal metastases. Our modification allows a significant differentiation of patients with spinal metastases with a prognosis of more or less than 12 months. PMID- 17848813 TI - Identification of consensus genes and key regulatory elements in 5-fluorouracil resistance in gastric and colon cancer. AB - BACKGROUND: 5-fluorouracil (5-FU) is widely used in the treatment of gastric and colorectal cancer. Recent microrarray studies associated different gene lists with 5-FU resistance. A major challenge in the genomic era is to find the most validated genes, and to decipher the regulatory networks responsible for the expression changes in a set of co-regulated transcripts. Our aim was to find genes repeatedly associated with 5-FU resistance, and to identify transcription factors (TFs) having overrepresented binding sites (TFBSs) in the promoter regions of genes associated with 5-FU resistance. MATERIALS AND METHODS: The analyzed data originated from 5 different publications describing genome-wide gene expression patterns associated with 5- FU resistance in gastric and colorectal cancer. First, a data warehouse containing all genes associated with resistance was set up. 39 genes were identified which were repeatedly associated with resistance. Of these, using the EZ-Retrieve web service, proximal promoter sequences were available for 33 genes. The MotifScanner software was used to detect TFBSs in this set of sequences. RESULTS: A total of 200 different TFBSs were identified. Using the statistics tool of the Java program TOUCAN, 4 binding sites were found to be significantly overrepresented: NFKappaB50 (p = 0.01), EGR2 (p = 0.027), EGR3 (p = 0.007), and NGFIC (or EGR4) (p = 0.001). These genes intercept apoptotic pathways at multiple locations in the tumor cells. CONCLUSION: We identified a consensus gene list associated with 5-FU resistance, performed an in silico comparative promoter analysis, and highlighted the potential implication of some TFs in the development of chemoresistance. PMID- 17848814 TI - Randomized controlled trial of a structured training program in breast cancer patients with tumor-related chronic fatigue. AB - BACKGROUND: Cancer-related fatigue is the most disabling symptom experienced by breast cancer patients following the cancer treatment. The positive effects of physical activity in the rehabilitation of breast cancer patients are documented in several studies. In a randomized controlled study the effects of a structured physical training program on fatigue and health-related quality of life were evaluated. PATIENTS AND METHODS: 63 breast cancer patients with cancer-related chronic fatigue were randomized at the beginning of the inpatient rehabilitation. The control group received the standard complex rehabilitation program, the intervention group a structured physical training program and additional muscle strength and aerobic exercises. The effects of the treatment were evaluated by questionnaires at the start of rehabilitation (t1), end of rehabilitation (t2), and 3 months after t2 (t3). Isometric muscle strength and aerobic capacity were evaluated at t1 and t2. RESULTS: There was an improvement of muscle strength at the end of rehabilitation for both groups. The increase from t1 to t2 was significantly higher for the training group. The scores for global quality of life, physical well-being, and functionality increased from t1 to t2, but further improvement in the follow-up (t3) was only observed in the training group. The cancer-related fatigue was significantly reduced in the training group from t1 to t3, however, not in the control group. CONCLUSIONS: Structured physical training programs initiated during inpatient rehabilitation and continuously practiced in the time thereafter can improve symptoms of chronic fatigue and quality of life in breast cancer patients. PMID- 17848815 TI - Improvement of safety profile of docetaxel by weekly administration in patients with metastatic breast cancer. AB - BACKGROUND: This is a retrospective cohort study on the safety and efficacy profiles of weekly docetaxel at varying doses in patients with pretreated metastatic breast cancer. PATIENTS AND METHODS: Twenty-five anthracycline pretreated patients received docetaxel administered on a weekly basis, as a one hour infusion, at various dosage levels (25, 30, 35, 40 mg/m2) depending on their baseline Karnofsky index. Each 8-week cycle consisted of 6 weeks of drug infusion, followed by a 2-week rest period. RESULTS: Of the 25 patients investigated, none achieved complete response (CR), while 9 patients showed partial response (PR), which corresponds to an overall response rate of 36%. Five patients (20%) maintained stable disease (SD), whereas 11 patients (44%) suffered tumor progression (PD) during treatment. Clinical response (defined as PR+SD) was achieved in 14 patients (56%). Median time to progression was 231 days (95% CI, 187-275). The baseline Karnofsky index was 87% +/- 9% (range: 70-100). Patients pretreated with anthracyclines only tended to have a better response than anthracycline/paclitaxel-pretreated patients (n = 6, p = 0.054). Higher dosages were associated with neurotoxicity, skin/nail toxicity, leukopenia, nausea/vomiting, fatigue/asthenia, peripheral edema, but not with diarrhea and alopecia. The cumulative dose per patient was largest for a weekly docetaxel dosage of 35 mg/m2 and almost as large for 30 mg/m2. CONCLUSION: Balancing toxicity vs. efficacy/cumulative dosage delivered, our results support weekly administration of docetaxel at dosages of 30-35 mg/m2 in metastatic breast cancer. Response in patients pretreated with anthracyclines and taxanes may be poorer than in those pretreated with anthracyclines only. PMID- 17848816 TI - Symptom-oriented follow-up of early breast cancer is not inferior to conventional control. Results of a prospective multicentre study. AB - BACKGROUND: The homogeneity of the schemes for follow-up care after curative surgical treatment of early breast cancer is still a matter of debate in Germany. We investigated whether symptom-oriented follow-up is equivalent in terms of survival rates to conventional surveillance based on scheduled tests. PATIENTS AND METHODS: In a prospective, non-randomised, multicentre cohort study carried out between 1995 and 2000, 244 patients underwent a conventional follow-up (scheduled laboratory tests including CEA and CA 15-3, chest X-rays and liver ultrasound). 426 patients were monitored in a symptom-oriented manner (additional tests only in the case of symptoms indicating possible recurrence). Mammography, structured histories and physical examinations were done regularly in both branches. 1,108 patients did not participate in the project. They represent 'real world patients', unaffected by the implications of a study. RESULTS: The symptom oriented follow- up group produced results not inferior to those of the intensive one (p < 0.05) in terms of overall and relapse-free survival. Furthermore, no difference was indicated in terms of overall survival between study participants and the 'real world patients' (p = 0.316). CONCLUSION: The results confirm that regular imaging and laboratory tests have no relevant effect on overall survival of patients after curative primary therapy of early breast cancer and support the implementation of a symptom-oriented routine follow-up. PMID- 17848817 TI - Renal cell cancer presented with leptomeningeal carcinomatosis effectively treated with sorafenib. AB - BACKGROUND: Sorafenib has been approved in the U.S. and the European Union for patients with advanced renal cell cancer (RCC). There is evidence that treatment with sorafenib can achieve partial remissions in patients with brain metastases of RCC. CASE REPORT: We report of a patient with leptomeningeal carcinomatosis of RCC, who 10 days after initiation of sorafenib therapy showed a noticeable decrease in contrast enhancement of the tumor in a magnetic resonance imaging (MRI) scan of the brain. This partial response was verified by an MRI scan on day 74. DISCUSSION: Results of a sub-evalution of a randomized phase III trial show that sorafenib offers encouraging activity in the treatment of patients with RCC and brain metastases. CONCLUSION: This case shows that sorafenib can achieve rapid tumor response in a patient with leptomeningeal carcinomatosis of RCC. This partial remission can persist for at least 10 weeks. PMID- 17848818 TI - Paravasation with cyclophosphamide--case report of tissue necrosis in a patient with primary breast cancer. AB - BACKGROUND: Paravasation is a rare but severe complication of treatment with cytotoxic agents. Some anticancer drugs are considered to be of high toxicity (vesicant), some are merely irritant, and some are regarded as nearly non-toxic to healthy tissue as is the case with cyclophosphamide. CASE REPORT: In this report, we present the first case of severe tissue damage caused by a paravasation of cyclophosphamide in a breast cancer patient receiving chemotherapy. CONCLUSION: Therefore, every attending oncological physician should be aware of the possibility of severe tissue damage as a consequence of cyclophosphamide paravasation. PMID- 17848819 TI - Syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by vinorelbine treatment of metastatic breast cancer. AB - BACKGROUND: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is known as a rare adverse event with chemotherapy. We report the case of a SIADH occurring after vinorelbine treatment. CASE REPORT: In a 79-year-old woman breast cancer was first diagnosed in 2000. Three years after the first diagnosis the patient developed bone and liver metastases. Seven days after receiving the 1st course of palliative chemotherapy with vinorelbine the patient suffered from decreased mental awareness, fatigue, and physical weakness. After the diagnosis of SIADH based on laboratory findings in combination with clinical symptoms, we started therapy with balanced fluid intake and intravenous infusion of normotonic saline. CONCLUSION: The development of SIADH as a rare adverse event with vinorelbine treatment has to be taken into consideration. PMID- 17848820 TI - Adenocarcinoma of the appendix and a Meckel's diverticulum in a case of acute appendicitis. PMID- 17848828 TI - Meditation-induced psychosis. AB - BACKGROUND: Meditation is a self-regulatory psychological strategy that is frequently applied in Western as well as non-Western countries for different purposes; little is known about adverse events. SAMPLING AND METHODS: A male patient is described who developed an acute and transient psychosis with polymorphic symptomatology after meditating. A literature search for psychotic states related to meditation was carried out on PubMed, Embase and PsycInfo. RESULTS: In the case presented a diagnosis of acute polymorphic psychotic disorder was made. Other case reports dealt with either a relapse of a pre existent psychotic disorder or with a brief psychotic reaction in patients without a psychiatric history. CONCLUSION: Meditation can act as a stressor in vulnerable patients who may develop a transient psychosis with polymorphic symptomatology. The syndrome is not culture bound but sometimes classified in culture-bound taxonomies like Qi-gong Psychotic Reaction. PMID- 17848829 TI - Clonal pluralization of self, relatives and others. AB - Delusional misidentification syndromes are a fascinating aspect of the psychopathology of psychotic patients. Recent psychiatric literature has mentioned a new variant of misidentification syndrome. Termed 'clonal pluralization', it differs from the typical misidentification syndromes. Essentially, the basic assumption of clonal pluralization is the belief that there are many physically and psychologically identical copies of a given original. This report presents a patient with schizophrenia who believed in triplicate copies of herself and others. PMID- 17848830 TI - A special coincidence of erotomania and Fregoli syndrome. PMID- 17848831 TI - Perceptions on remission and recovery in schizophrenia. PMID- 17848832 TI - Dissociative disorders among chronic and severely impaired psychiatric outpatients. PMID- 17848833 TI - Leptin-to-adiponectin ratio as independent predictor of insulin sensitivity during growth in overweight Hispanic youth. AB - Because leptin and adiponectin are counter-regulated in vivo and exert opposing effects on glucose metabolism, fat oxidation and insulin sensitivity, the ratio of leptin-to-adiponectin has been investigated as a potential atherogenic index, suggesting that the index is a better biomarker for atherosclerotic risk in obese Type 2 diabetic patients than either leptin or adiponectin alone. However, no information is available regarding the leptin-to-adiponectin ratio during adolescence in Hispanic adolescents. Therefore, the present study was designed to investigate the leptin-to-adiponectin ratio during growth and to establish whether the leptin-to-adiponectin ratio is a better predictor for insulin sensitivity compared to leptin and adiponectin alone in a regression model. From the age of 8 to 14, the leptin-to-adiponectin ratio increased from 2.0+/-0.8 to 5.8+/-2.2 in girls, with no significant change noted in boys (gender x age interaction p=0.007). In a multiple regression analysis, including both adiponectin and leptin as independent variables, leptin and adiponectin explained 5% of the variation in insulin sensitivity independent of gender, age, Tanner stage, total fat mass and lean body mass (p for R2-change <0.001). The leptin-to adiponectin ratio also explained 5% of the variation in insulin sensitivity, after controlling for the same covariates (p for R2-change <0.001). These data indicate that the leptin-to-adiponectin ratio is not a better predictor of insulin sensitivity during growth than the additive effects of leptin and adiponectin levels. PMID- 17848834 TI - Peripheral blood levels of thyroglobulin mRNA and serum thyroglobulin concentrations after radioiodine ablation of multinodular goiter with or without pre-treatment with recombinant human thyrotropin. AB - We investigated the effect of therapeutic doses of radioiodine (RAI) on peripheral serum messenger thyroglobulin RNA (Tg mRNA) and serum thyroglobulin (sTg) in patients with multinodular goiter (MNG) preceded or not by treatment with recombinant human TSH (rhTSH). Fourteen patients with large MNG (91-542 ml) received RAI (550-2960 MBq). Half of the patients received 0.45 mg of rhTSH prior to the treatment (RAI+rhTSH group) and half did not (RAI group). Patients' blood samples were collected before and 24, 48, and 72 h; 7 and 30 days; and 6, 9, and 12 months after RAI treatment. Serum Tg was measured by immunoradiometric assay, serum anti-Tg by radioimmunoassay, and quantification of circulating Tg mRNA was performed by real-time PCR. The shrinkage of MNG volume was documented by serial computed tomography (CT) scans before, 6 and 12 months after RAI. Peak Tg mRNA and sTg were reached earlier in the RAI+rhTSH group (24 h and 48 h) than in the RAI group (7 days). Both declined after the peak and the lowest levels were observed at 12 months. The mean reduction of the thyroid volume was 19.8% (RAI group) and 30.3% (RAI+rhTSH group) at 6 months (ns) and 32.8% RAI and 52.5% (RAI+rhTSH group) at 12 months (p<0.05). After RAI treatment there was a significant and positive correlation between goiter volume and sTg only in the RAI group (r=0.7; p=0.032). Serum anti-Tg had a transitory and relatively small elevation in 3 and 2 patients, respectively, in the RAI and RAI+rhTSH groups. We concluded that after RAI ablation of MNG there is a rapid release of Tg into the serum possibly from the colloid, which is followed by an elevation of serum Tg mRNA that may be due to an increased release of follicular cells into the blood stream. Both phenomena are enhanced by the use of rhTSH before RAI treatment as a consequence of a more effective and prolonged radiation exposure of the thyroid follicles. PMID- 17848835 TI - Cost of management of invasive growth hormone-secreting macroadenoma. AB - BACKGROUND: At the time of diagnosis, macroadenomas represent 60-80% of GH secreting adenomas, of which 25-30% are invasive macroadenomas. These aggressive tumors have the worst surgical success rates in terms of cure, and often need several therapeutic approaches in order to control disease status. Acromegalic patients are subject to increased mortality and important health resource consumption related to their associated co-morbidities, in addition to the costs that are related to diagnosis itself and initial treatment of the disease. OBJECTIVE: Assessment of the cost of initial management and outcome of acromegalic patients with invasive pituitary adenomas. STUDY DESIGN: Retrospective and observational study of review of records. SETTING: Two tertiary hospitals. PATIENTS: 11 consecutive patients between 18 and 80 yr old diagnosed with acromegaly due to an invasive pituitary macroadenoma. INTERVENTION: Collection of data of biochemical and radiological tests, specialist visits, hospitalisation, surgery, pharmacological and radiotherapy treatment at diagnosis and over 4 yr of follow-up after initial treatment. Costs were evaluated using the data of the Centre for Health Economics and Social Policy Studies and the Official College of Pharmacists of Spain. MAIN OUTCOME MEASURE: Global and patient/yr follow-up costs of illness. RESULTS: The mean costs for acromegaly for the period of follow-up ranged from 7,072 to 9,874 euro/patient/yr, for biochemically non-controlled (no.=6) and controlled patients (no.=5) respectively. The most important cost in the perioperative period was for admission in the intensive care unit. After surgery, SS analogues were the principal contributors to the economic burden. CONCLUSION: In this paper we have for the first time presented a pharmacoeconomic study of GH secreting invasive macroadenoma. The poor prognosis of our cohort of patients and the higher rate of controlled patients and normal IGF-I levels warrant the employment of multiple therapeutic options. The cost associated with this treatment in this complex disease of low prevalence is not excessive and can be supported by healthcare services. PMID- 17848836 TI - Demographic and clinical features of patients with subacute thyroiditis: results of 169 patients from a single university center in Turkey. AB - BACKGROUND: Turkey is an endemic area for thyroid diseases. The Aegean region is well documented for increased prevalence of thyroid disorders. In this study we investigated the demographic and clinical features of subacute thyroiditis (SAT) patients who had been diagnosed and treated in Ege University. METHODS: The hospital files of patients admitted to the endocrinology clinic of Ege University between January 1987 and December 2001 were retrospectively evaluated. Patients who had been diagnosed as having any thyroid disorder were determined. RESULTS: 176 fulfilled diagnostic criteria for SAT. The majority of patients with SAT were diagnosed as having subacute granulomatous thyroiditis (169/176) (134 females, 35 males, mean age 34.0+/-17.8 yr); 69% of the patients were between 30-50 yr of age. Thyroid pain was present in 97.1% of female patients, and in 100% of male patients. High fever was evident in 78 patients (46.2%). Mean erythrocyte sedimentation rate (ESR) was 43.42+/-39.68 mm/h. Anti-thyroglobulin antibody was positive in 20%, and anti-thyroid peroxydase antibody was positive in 4% of patients. Among patients who were treated with non-steroidal anti-inflammatory drugs (NSAD) 10 female patients (10.6%), and 3 male patients (12%) developed recurrence of the disease. Among patients who were treated with prednisolone 7 female patients (17.5%), and one male patient (10%) developed recurrence. There was no significant difference regarding the recurrence rates between patients who were treated with NSAD and patients who were treated with prednisolone. CONCLUSION: With the exception of ESR, demographic, clinical, laboratory, and imaging findings and prognoses of our patients were comparable to the previous reports. PMID- 17848837 TI - Apolipoprotein E and lipoprotein lipase gene polymorphisms interaction on the atherogenic combined expression of hypertriglyceridemia and hyperapobetalipoproteinemia phenotypes. AB - The combination of hypertriglyceridemia (hyperTG) and hyperapobetalipoproteinemia (hyperapoB) is associated with an increased coronary artery disease (CAD) risk. Apolipoprotein (apo) E and lipoprotein lipase (LPL) genes are involved in the catabolism of triglycerides (TG)-rich apoB-containing lipoproteins (VLDL). Several apoE and LPL gene variants affecting CAD risk, plasma TG or apoB concentrations have an allelic frequency of >5% in the general population. This study examined the combined effect of frequent apoE and LPL gene polymorphisms on the expression of hyperTG and hyperapoB. ApoE (E2, E3, and E4) and LPL (D9N, N291S, G188E, and P207L) were genotyped and fasting lipid profiles were assessed among 1,441 French-Canadian subjects. Multivariate analyses were performed to estimate the relationship between apoE and LPL gene variants and the risk of hyperTG (TG>1.7 mmol/l) and hyperapoB (apoB>0.9 g/l). Compared to apoE3 carriers, the apoE4 allele significantly increased the risk of expressing the "hyperTG/hyperapoB" phenotype [odds ratio (OR)=1.95; p=0.014]. This risk was significantly exacerbated (OR=4.69; p=0.017) by the presence of frequent deleterious LPL gene variants in this population. The apoE2 allele was negatively associated with hyperTG/hyperapoB (OR=0.49; p=0.002) in the absence of a deleterious LPL gene variant. These results suggest that epistasis is a phenomenon to consider while assessing the CAD risk associated with gene variants or the effect of frequent alleles on high-risk lipid profiles. PMID- 17848838 TI - Primary hyperaldosteronism is associated with derangement in the regulation of the hypothalamus-pituitary-adrenal axis in humans. AB - Hippocampal mineralocorticoid receptors (MR) play a major role in the control of hypothalamus- pituitary-adrenal (HPA) axis. The functional profile of HPA axis and the impact of MR blockade under chronic exposure to mineralocorticoid excess are unknown. To clarify this issue, ACT H, cortisol, and aldosterone secretions were studied in 6 patients with primary hyperaldosteronism (HA) and 8 controls (NS) during placebo, placebo+human CR H (hCR H) (2 microg/kg iv bolus at 22:00 h), potassium canrenoate (CAN, 200 mg iv bolus at 20:00 h followed by 200 mg infused over 4 h) or CAN+hCR H. During placebo, both aldosterone and ACT H levels were higher (p<0.01) in HA than in NS, while cortisol levels were not significantly different. Both HA and NS showed significant ACT H and cortisol responses to hCR H (p<0.004), although the hormonal responses in HA were higher (p<0.02) than in NS. CAN infusion did not modify aldosterone levels in both HA and NS. Under CAN infusion, ACT H showed progressive rise in NS (p<0.05) but not in HA, while cortisol levels showed a significant (p<0.05) but less marked and delayed increase in HA compared to NS. CAN enhanced hCRH-induced ACTH and cortisol responses in NS (p<0.05), but not in HA. In conclusion, in humans primary hyperaldosteronism is associated with deranged function of the HPA axis. In fact, hyperaldosteronemic patients show basal and hCR H-stimulated HPA hyperactivity that is, at least partially, refractory to further stimulation by mineralocorticoid blockade with canrenoate. Whether this hormonal alteration can influence the clinical feature of hypertensive patients with primary hyperaldosteronism needs to be clarified. PMID- 17848839 TI - Early abnormalities of left ventricular myocardial characteristics associated with subclinical hyperthyroidism. AB - The aim of the present study was to analyze heart function in subclinical hyperthyroidism (sHT) in otherwise healthy subjects by new methods using intramyocardial ultrasonic techniques. Twenty-four newly diagnosed and untreated sHT patients (20 women, 4 men; mean age: 42+/-4 yr) and 24 sex- and age-matched healthy volunteers were studied. All subjects were submitted to conventional 2D color-Doppler echocardiography, pulsed wave tissue Doppler imaging (PWTDI) for the analysis of diastolic function, color Doppler myocardial imaging (CDMI) for the analysis of regional strain and strain rate (SR) expression of regional myocardial deformability, and to integrated backscatter (IBS) for the evaluation of intrinsic contractility and tissue characterization. Regional myocardial systolic strain findings were significantly higher in sHT patients when compared with controls (p<0.001). Considering diastolic SR, the early phase of diastolic SR was compromised in sHT subjects as compared with controls (p<0.001). Cyclic variation index (CVI), expression of intrinsic contractility, was significantly higher in sHT subjects in comparison with controls (p<0.0001). IBS values were comparable between the 2 study groups. In conclusion, the present study suggests that in patients with sHT early systolic hyperdeformability and hypercontractility are present, together with impairment of both active and passive phases of diastole. On the contrary, no left ventricular hypertrophy or other structural alterations are documented. PMID- 17848840 TI - Basal insulin supplementation in Type 1 diabetic children: a long-term comparative observational study between continuous subcutaneous insulin infusion and glargine insulin. AB - No long-term data are available on the efficacy of glargine insulin in comparison with continuous sc insulin infusion (CSII) in children and adolescents affected by Type 1 diabetes (T1D). Our aim was to compare the 2-yr efficacy of the 2 insulin approaches, in order to know how to best supply basal insulin in these patients. Thirty-six 9 to 18-yr-old consecutive children with at least 3 yr previous T1D diagnosis were enrolled. As part of routine clinical care, the patients consecutively changed their previous insulin scheme (isophane insulin at bedtime and human regular insulin at meals) and were randomly selected in order to receive either multiple daily injections (MDI) treatment with once-daily glargine and human regular insulin at meals, or CSII with aspart or lispro insulin. Both groups showed a significant decrease in glycosylated hemoglobin (HbA1c) values during the 1st year of therapy, though only in the CSII treated children was the decrease also observed during the 2nd year. The overall insulin requirement significantly decreased only in the CSII group and exclusively during the 1st year, while no significant differences were observed concerning body mass index SD score, severe hypoglycemic episodes and basal insulin supplementation. The work illustrates the first long-term study comparing the efficacy of CSII to MDI using glargine as basal insulin in children. Only with CSII were better HbA1c values obtained for prolonged periods of time, so that CSII might be considered the gold standard of intensive insulin therapy also for long-term follow-ups. PMID- 17848841 TI - Efficacy and safety of a new ready-to-use recombinant human growth hormone solution. AB - We report 24-month interim results of two multicenter phase III studies in previously untreated children with growth failure secondary to GH deficiency (GHD) that were paramount to the development of a new recombinant human GH (rh- GH, somatropin), approved as the first 'biosimilar' in Europe. Study 1 consisted of 3 parts performed in 89 children. The objective was to compare efficacy and safety of the lyophilized formulation of the new somatropin [Somatropin Powder (Sandoz)] with a licensed reference rhGH preparation and the liquid formulation of the new somatropin [Somatropin Solution (Sandoz)] and to assess long-term efficacy and safety of this ready-to-use Somatropin Solution. Study 2 was performed in 51 children and designed to demonstrate efficacy and safety of Somatropin Powder and to confirm its low immunogenic potential; rhGH was given sc at a daily dose of 0.03 mg/kg. Primary [body height, height SD score (HSDS), height velocity, and height velocity (HV) SD score (HVSDS)] and secondary [IGF-I and IGF binding protein 3 (IGFBP-3)] efficacy endpoints and safety parameters were assessed regularly. In study 1, all treatments showed comparable increases in growth. The baseline-adjusted difference between Somatropin Powder and the reference rhGH product in mean HV was -0.20 cm/yr (95% confidence interval (CI) [ 1.34;0.94]) and in mean HVSDS was 0.76 (95% CI [-0.57;2.10]) after 9 months. These very small differences demonstrate comparable therapeutic efficacy between the two treatments. The results of study 2 were consistent with those seen in study 1. Equivalent therapeutic efficacy and clinical comparability in terms of safety and immunogenicity between Somatropin Powder and the reference rhGH product and between Somatropin Powder and Somatropin Solution was demonstrated. The safety and immunogenicity profiles were similar and as expected from experience with rhGH preparations. PMID- 17848843 TI - Pregnancy in a woman with Turner syndrome and celiac disease. AB - BACKGROUND: Studies on fertility in women with Turner syndrome have shown that spontaneous pregnancies occur in about 2-7% of patients. Fertility problems and obstetrical complications are frequently observed in untreated patients with celiac disease. We report the case of a patient, affected by Turner syndrome and celiac disease, in whom a spontaneous pregnancy occurred. CASE: One patient affected by Turner syndrome at the age of 30 yr conceived spontaneously. Celiac disease was diagnosed during pregnancy. The pregnancy progressed uneventfully. After 39 weeks of gestation, she vaginally delivered a normal male infant. CONCLUSION: Our patient had a successful pregnancy, giving birth to a healthy child, although she presented two pathological conditions affecting fertility and pregnancy outcome: Turner syndrome and celiac disease. PMID- 17848844 TI - Atypical thymic carcinoid in multiple endocrine neoplasia type 1 syndrome. AB - An asymptomatic, non-smoker patient carrier of a multiple endocrine neoplasia syndrome type 1 (MEN1) mutation was diagnosed with invasive atypical thymic carcinoid tumor. After surgical treatment the tumor reappeared albeit without metastasis. Thymic carcinoid is a well-known cause of mortality in MEN1, and usually metastatic disease is present at diagnosis. Male sex, smoking, and previous hyperparathyroidism probably play a role in the pathogenesis of this neoplasia. PMID- 17848845 TI - TSH-secreting adenomas: rare pituitary tumors with multifaceted clinical and biological features. AB - TSH-secreting pituitary adenomas (TSH-omas) are a rare cause of hyperthyroidism in clinical practice. As their diagnosis is often delayed, these tumors are mostly diagnosed as macroadenomas, preventing an effective and radical cure and leading to serious local and systemic comorbidities. In addition to neurosurgery, medical therapy with the effective and tolerable SS analogs is a fundamental tool for the treatment of TSHomas. We report 3 cases of TSH-macroadenomas which displayed different clinical presentations. All patients showed increased free thyroid hormone levels with inappropriately normal (2 patients) or high (1 patient) TSH levels. Magnetic resonance imaging (MRI)/computed tomography (CT) evidenced a pituitary macroadenoma and octreoscan was positive in all patients. In the 2 patients who underwent neurosurgery, hormonal hypersecretion by the tumor normalized. Histology showed nuclear pleomorphism and fibrosis, whereas immunohistochemistry showed positivity for TSH and, in a lesser amount, for FSH. In one of these patient (case 1), however, the presence of a tumor remnant inside the left cavernous sinus prompted us, in accordance with the patient, to start therapy with octreotide- long-acting release. As the third patient had a cardiac comorbidity which contraindicated neurosurgery, he underwent satisfactory treatment with long-acting SS analogs alone which normalized thyroid hormone levels. In this case, previous treatment with amiodarone confused and delayed the correct diagnosis of TSH-oma. As a result of improved laboratory and morphological techniques, TSH-omas should currently be diagnosed in early stages, thus enabling most patients to be managed satisfactorily through a combined approach. PMID- 17848842 TI - Looking beyond low bone mineral density: multiple insufficiency fractures in a woman with post-menopausal osteoporosis on alendronate therapy. AB - Insufficiency fractures occur most commonly in the pelvic girdle and in the sacrum, followed by the tibia and the femoral neck. Insufficiency fractures of the femoral diaphyses are rare, with only few reported cases in the literature. The strongest associations exist with untreated osteoporosis. We describe an unusual case of multiple insufficiency fractures in a 73-yr-old Chinese woman who presented with a 10-month history of bilateral groin pain and difficulty with walking in the absence of trauma, diagnosed 18 months following the commencement of anti-resorptive therapy with alendronate. The pathogenesis of such insufficiency fractures is poorly understood, but next to low bone mineral density and micro-architectural damage likely involves other components such as changes in bone turnover and patient-related factors (e.g. non-compliance). This case report and review of the literature draws attention to some of the challenges in the diagnosis and management of such rare insufficiency fractures. PMID- 17848846 TI - Dipeptidyl peptidase 4 (DPP-4) inhibitors and their role in Type 2 diabetes management. AB - Dipeptidyl peptidase 4 (DPP-4) inhibitors are a new pharmacological class of drugs for treating Type 2 diabetes. They improve the capacity of the organism to control glycemia by increasing the levels of active incretins. Their mechanism of action is thus radically different from those of other anti-diabetic drugs currently available. DDP-4 inhibitors use a physiological mechanism to control hyperglycemia, by stimulating the secretion of insulin from beta-cells, decreasing the secretion of glucagon from pancreatic alpha-cells, and at the same time reducing the production of glucose by the liver. DDP-4 inhibitors have shown significant efficacy in maintaining reduced levels of glycosylated hemoglobin for up to 1 year. In vitro and animal studies have shown that they can inhibit apoptosis of beta-cells and favor their regeneration and differentiation. The oral DPP-4 inhibitors vildagliptin, sitagliptin, and saxagliptin are efficacious both alone and in association with other oral anti-diabetic agents and may be administered in a single daily dose. Lastly, they have substantial advantages with respect to other anti-diabetic drugs, since they involve a low risk of hypoglycemia and do not affect body weight. PMID- 17848847 TI - The role of 21-hydroxylase in the pathogenesis of adrenal masses: review of the literature and focus on our own experience. AB - An exaggerated response of 17- hydroxyprogesterone (17-OHP) to exogenous ACTH stimulation has been found in 30 to 70% of patients with incidentally discovered adrenal tumors, supporting the concept that congenital 21- hydroxylase deficiency may be a predisposing factor for adrenocortical tumorigenesis. Decreased expression of 21-hydroxylase gene has been observed in sporadic non-functioning adrenocortical adenomas and adrenocortical carcinomas, in agreement with the reduced steroidogenic activity found in these types of tumors. Screening studies for the presence of mutations in CYP21A2 gene, encoding 21-hydroxylase, in patients with sporadic adrenocortical tumors yielded discordant results. Overall, a higher frequency of germline 21-hydroxylase mutation carriers has been found among patients with adrenal tumors, including incidentalomas, than in the general population. However, the presence of mutations did not correlate with endocrine test results and tumor mass features, suggesting that 21-hydroxylase deficiency does not represent a relevant mechanism in adrenal tumorigenesis. Mechanisms leading to reduced 21-hydroxylase expression and activity are still unknown. PMID- 17848848 TI - Ultrasound-guided percutaneous laser ablation treatment in inoperable aggressive course anaplastic thyroid carcinoma: the introduction of a novel alternative palliative therapy--second experience in the literature. PMID- 17848849 TI - Case-control study design: spurious associations between exposure and outcome. PMID- 17848850 TI - Interventions in relation to occupational burnout: the population-based health 2000 study. AB - OBJECTIVE: To study participation in occupational and individual-focused interventions in relation to burnout. METHODS: We used data from a questionnaire, structured interview, national register of psychopharmacological prescriptions, and the Composite International Diagnostic Interview in a nationally representative Finnish sample of 3276 employees (30 to 64 years). RESULTS: When compared with employees free of burnout, the odds ratio of severe burnout for participation in occupational interventions was 0.41 (95% confidence interval [CI] = 0.26 to 0.65) and in individual-focused interventions 5.36 (95% CI = 3.14 to 9.17). Antidepressant prescriptions were 2.53 (95% CI = 1.04 to 6.15) times more common among those with severe burnout than among those without burnout after adjustment for depressive and anxiety disorders. CONCLUSIONS: Employees with burnout were less often targets of occupational interventions but participated more in individual-focused interventions when compared with other employees. The use of antidepressants among employees with severe burnout was not fully explained by coexisting depressive or anxiety disorders. PMID- 17848851 TI - Empirical evaluation of complex epidemiologic study designs: workplace exposure and cancer. AB - OBJECTIVE: To test whether a frequently used cohort-nested case-control study design exaggerated exposure-response relationships because of unrecognized study design bias. Our aim was to evaluate empirically the performance of this complex study design. METHODS: We applied the design from one such study to a closely related cohort using randomly selected probands as cases. Values for average exposures were assigned to probands equal to, greater than, and less than those assigned to controls (matches). RESULTS: Under certain lag scenarios, the nested study design produced higher average exposure in probands compared with their matches, even when this was clearly not the case. CONCLUSIONS: Empirical evaluation demonstrated that the study design produced a biased case-control lagged exposure difference under the null hypothesis and could not distinguish qualitatively between null and alternate hypotheses. Empirical evaluation provided a useful check on results generated from a complex study design. It gave useful insight into the behavior of the index study design that was not otherwise readily deducible. PMID- 17848852 TI - The impact of early workplace-based return-to-work strategies on work absence duration: a 6-month longitudinal study following an occupational musculoskeletal injury. AB - OBJECTIVES: To examine, using administrative and self-reported data, the relationship between early return-to-work (RTW) strategies and work absence duration. METHODS: Using a cohort of 632 claimants with work-related musculoskeletal injuries, Cox proportional hazard analyses were performed with RTW strategies measured 1 month after injury as predictors. Outcomes were 6-month self-reported work absence duration and time receiving wage replacement benefits from an administrative database. RESULTS: Work accommodation offer and acceptance and advice from health care provider (HCP) to the workplace on re-injury prevention were significant predictors of shorter work absence duration indexed by both self-report and administrative data. Receiving an ergonomic visit was a significant predictor of shorter duration receiving benefits only. CONCLUSIONS: Analyses using administrative and self-reported indices of work absence generally converged. Work accommodation and targeted HCP communication with the workplace are critical for effective early RTW interventions. PMID- 17848853 TI - Overweight and obesity as predictors of absenteeism in the working population of the Netherlands. AB - OBJECTIVE: To determine the relation between body mass index (BMI) and absenteeism. METHODS: Data were collected in a prospective cohort study (n = 1284). Multilevel analyses (linear mixed model with random intercept) with two levels (employee and company) were used to test whether BMI was related to duration and frequency of absenteeism and whether this relation was influenced by sports participation. RESULTS: Obese employees were absent 14 days a year more than normal-weight employees. Also the frequency of absenteeism of more than 7 days was significantly higher. The differences in absenteeism between obese and normal-weight employees were larger for employees who did not practice sport regularly. CONCLUSIONS: Obese employees are more often absent and are absent longer, especially when they do not practice sport regularly. An active company policy to prevent obesity is needed, both from a health and a business efficiency perspective. PMID- 17848854 TI - A pilot study testing the effect of different levels of financial incentives on weight loss among overweight employees. AB - OBJECTIVE: To test the ability of two levels of modest financial incentives to encourage weight loss among overweight employees. METHODS: This study used a randomized design with measurements at baseline, 3, and 6 months and two levels of financial incentives ($7 and $14 per percentage point of weight lost). Payments were structured so that all participants had equal ability to obtain the incentives during the study period. RESULTS: At 3 months, participants with no financial incentive lost 2 pounds, those in the $7 group lost approximately 3 pounds, and those in the $14 group lost 4.7 pounds. Between baseline and 6 months, when the financial gains were equalized, weight losses were similar across groups. CONCLUSION: This study revealed that modest financial incentives can be effective in motivating overweight employees to lose weight. PMID- 17848855 TI - Job strain, life events, and sickness absence: a longitudinal cohort study in a random population sample. AB - OBJECTIVE: To examine job strain, adverse life events, and their co-occurrence as predictors of sickness absence. METHODS: Random sample-based mail survey data on 1806 Finns in gainful employment were linked to sickness absence records (1987 1998) from national health registers. Generalized linear models with negative binomial distribution assumption were applied. RESULTS: After adjustment for demographic characteristics and health behavior, job strain (rate ratio [RR] 1.73; 95% confidence interval [CI] = 1.21-2.48), but not life events, independently predicted increased rate of sickness absence among men. The opposite was true for women, (RR for life events 1.39; 95% CI = 1.10-1.75). No statistically significant interaction between job strain and life events was detected. CONCLUSION: In addition to job strain, strain originating in private life should be kept in mind when the need for sickness absence of women employees is evaluated within health care. PMID- 17848856 TI - Mortality and cancer experience of Quebec aluminum reduction plant workers. Part I: The reduction plants and coal tar pitch volatile (CTPV) exposure assessment. AB - OBJECTIVES: This paper presents the exposure assessment and job-exposure matrix (JEM) used to estimate coal tar pitch volatile (CTPV) exposure for a study of mortality and cancer incidence in aluminum smelter workers in Quebec, Canada. METHODS: Historical CTPV exposure was assessed by estimating benzene-soluble material (BSM) and benzo[a]pyrene (B[a]P) levels for combinations of job and time period. Estimates were derived by using several procedures including averaging measurement data, a deterministic mathematical model using process-related correction factors, and expert-based extrapolation. RESULTS: The JEM comprised 28,910 jobs, covering 7 facilities from 1916 to 1999. Estimated exposures ranged from 0.01 microg/m(3) to 68.08 microg/m(3) (B[a]P) and 0.01 mg/m(3) to 3.64 mg/m(3) (BSM) and were lowest before 1940 and after 1980. CONCLUSION: This methodology constitutes an improvement compared with methods used for previous studies of the Quebec cohort. PMID- 17848857 TI - Severe illness in furniture makers using a new glue: 1-bromopropane toxicity confounded by arsenic. AB - OBJECTIVE: To describe the illnesses of four workers with high concentrations of serum bromide after exposure to glue containing 1-bromopropane (1-BP). METHODS: We reviewed all available clinical records, examined the workers, and obtained additional urinary arsenic values. We used standard autoanalyzer and other routine methods for blood and urinalysis. RESULTS: All four workers had symptoms and abnormal physical findings when hospitalized, remaining symptomatic with abnormal examinations 3 months later. Milder symptoms persisted in two workers, 8 years after their initial illnesses. Both have returned to work. Follow-up was unavailable for the other two workers. CONCLUSIONS: Severe illness occurred in four gluers after 1-BP exposures associated with elevated levels of serum bromide. All had elevated urinary arsenic concentrations, the source of which remains unknown, but which confound interpretation of the abnormal bromide levels and clinical findings present during the acute illnesses. PMID- 17848858 TI - Production of silicon metal and alloys is associated with accelerated decline in lung function: a 5-year prospective study among 3924 employees in norwegian smelters. AB - OBJECTIVES: To investigate the association between decline in lung function and production of alloys in the Norwegian smelting industry. METHODS: All employees (N = 3924) were examined annually for 5 years (16,570 examinations). The employees were classified into three categories: 1) line operators (employed full time in the production line), 2) nonexposed (no exposure last year), and 3) non line operators (remaining subjects). The outcome variable was expressed as forced expiratory volume in 1 second per squared height (FEV1/height(2)). RESULTS: In the subcohorts of the ferrosilicon/silicon metal and silicon carbide industries, the differences between line operators and nonexposed workers were -2.3 (-4.3 to 0.3) (CI = 95%) and -5.6 (-10.4 to -0.7) mL/(m(2) x year), respectively. CONCLUSION: Line operators in the ferrosilicon/silicon metal and silicon carbide industries had a steeper annual decline in FEV1/height compared with nonexposed workers. PMID- 17848859 TI - Air emissions from Wagerup alumina refinery and community symptoms: an environmental case study. AB - Commissioning of a liquor burner at Wagerup alumina refinery gave rise to complaints of malodor and irritation among employees. Subsequently, community members complained about odor and various health issues. Some employees and community members were diagnosed by general practitioners as having multiple chemical sensitivity. After implementation of emission controls, the situation improved; however, community concerns lingered. This paper describes this experience and summarizes several recent investigations including air dispersion modeling, health risk assessment, ambient air quality monitoring, and complaints analyses. It is concluded that refinery emissions currently present negligible risks of acute or chronic health effects including cancer. Communication of these findings has been generally well received, but modifying the perception of risk among some elements of the community has been difficult. Organizations need to effectively address both technical and perception of risk issues. PMID- 17848860 TI - Quality of life and employment status of workers with Western red cedar asthma. AB - OBJECTIVE: The impact of current employment status and other factors on quality of life was evaluated for workers diagnosed with western red cedar asthma in British Columbia, Canada. METHODS: Telephone interviews by questionnaire included the Short Form 36 (SF-36) and Marks Asthma quality-of-life instruments. RESULTS: Of the 302 subjects contacted, 70.5% (n = 213) participated. Employment status was the most consistent predictor of quality-of-life domains, with highest scores for employed subjects, particularly those who were no longer exposed to red cedar. Subjects who had quit work because of their asthma had worse scores, particularly for vitality and general health perceptions. Other factors independently associated with specific aspects of poor quality of life were having asthma-like symptoms, taking medication, and not being married. CONCLUSIONS: Continued employment was associated with better quality of life for workers with western red cedar asthma. PMID- 17848861 TI - Occupational Medicine Forum. PMID- 17848864 TI - Deep brain stimulation. AB - BACKGROUND: Deep brain stimulation (DBS) for the treatment of neurologic diseases has markedly increased in popularity over the past 15 years. This review primarily focuses on movement disorder applications and efficacy of DBS, but also briefly reviews other promising new and old uses of DBS. REVIEW SUMMARY: A multidisciplinary team consisting of a movement disorders neurologist, a functional neurosurgeon, and a neuropsychologist optimally selects patients for DBS. Patients must be significantly disabled despite optimal medical therapy and be cognitively healthy without significant psychiatric disorders. Although this surgery is elective, it should not be withheld until the patient suffers marked loss of quality of life. Patients must have support from caregivers and postoperatively multiple DBS programming visits may be required. DBS of the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi) significantly improves motor performance, activities of daily living, and quality of life in advanced Parkinson disease. In addition, STN DBS allows for marked reductions of antiparkinson medication. Stimulation of the ventralis intermedius nucleus of the thalamus is an effective treatment for essential tremor with sustained long-term effects. The GPi may be the preferred site of stimulation for dystonia with movement scores typically improved by 75% in patients with primary dystonia. CONCLUSIONS: DBS is an effective surgical treatment for movement disorders with sustained long-term benefits. Further research is ongoing to better understand the mechanism of DBS, refine the hardware to improve efficacy and reduce adverse effects, and identify additional applications and new anatomic targets. PMID- 17848865 TI - Pearls in patient selection for deep brain stimulation. AB - BACKGROUND: Deep brain stimulation (DBS) has emerged as an important treatment for medication refractory movement and neuropsychiatric disorders. General neurologists and even general practitioners may be called upon to screen potential candidates for DBS. The patient selection process plays an important role in this procedure. REVIEW SUMMARY: In this article, we discuss "pearls" for the clinician who may be called upon to identify appropriate candidates for DBS. Additionally, we will discuss the important points that should be considered when referring patients for surgical intervention. CONCLUSION: Diagnosis, response to levodopa, cognitive status, psychiatric status, access to care, and patient expectations are all essential elements of the patient selection process for DBS. These areas must be adequately addressed prior to any surgical procedure. PMID- 17848866 TI - Limbic encephalitis and variants: classification, diagnosis and treatment. AB - BACKGROUND AND OBJECTIVE: Recent studies suggest that a substantial number of patients with autoimmune limbic encephalitis may improve if properly diagnosed and treated. This is due, in part, to the increasing recognition of disorders that associate with antibodies to neuronal cell membrane antigens. This review focuses in these disorders, framed in a clinically useful immunologic classification of limbic encephalitis. REVIEW SUMMARY: Patients with limbic encephalitis usually present with rapidly progressive short-term memory deficits, psychiatric symptoms, and seizures. After excluding viral and systemic autoimmune disorders, many patients with limbic encephalitis (paraneoplastic or not) have cerebrospinal fluid inflammatory findings, EEG or MRI abnormalities in the temporal lobes, and antineuronal antibodies. These antibodies are directed against 2 broad categories of antigens: (1) intracellular or classic paraneoplastic antigens, including Hu, Ma2, CV2/CRMP5, and amphiphysin among others, and (2) cell membrane antigens, including voltage-gated potassium channels, N-methyl-D-aspartate receptor, and others expressed in the neuropil of hippocampus and cerebellum (pending characterization). Whereas the disorders related to the first category of antibodies associate with cancer (lung, testis and other), prominent brain infiltrates of cytotoxic T-cells, and limited response to treatment, the disorders related to the second category of antibodies associate less frequently with cancer (thymoma, teratoma), seem to be antibody mediated, and respond significantly better to immunotherapy. CONCLUSIONS: Once considered an extremely rare disorder, almost always related to cancer, and refractory to treatment, limbic encephalitis is now regarded as a relatively frequent disorder, often unrelated to cancer, and with clinical-immunologic variants that respond to treatment. PMID- 17848867 TI - Dextromethorphan as a potential neuroprotective agent with unique mechanisms of action. AB - BACKGROUND: Dextromethorphan (DM) is a widely-used antitussive. DM's complex central nervous system (CNS) pharmacology became of interest when it was discovered to be neuroprotective due to its low-affinity, uncompetitive N-methyl D-aspartate (NMDA) receptor antagonism. REVIEW SUMMARY: Mounting preclinical evidence has proven that DM has important neuroprotective properties in various CNS injury models, including focal and global ischemia, seizure, and traumatic brain injury paradigms. Many of these protective actions seem functionally related to its inhibitory effects on glutamate-induced neurotoxicity via NMDA receptor antagonist, sigma-1 receptor agonist, and voltage-gated calcium channel antagonist actions. DM's protection of dopamine neurons in parkinsonian models may be due to inhibition of neurodegenerative inflammatory responses. Clinical findings are limited, with preliminary evidence indicating that DM protects against neuronal damage. Negative findings seem to relate to attainment of inadequate DM brain concentrations. Small studies have shown some promise for treatment of perioperative brain injury, amyotrophic lateral sclerosis, and symptoms of methotrexate neurotoxicity. DM safety/tolerability trials in stroke, neurosurgery, and amyotrophic lateral sclerosis patients demonstrated a favorable safety profile. DM's limited clinical benefit is proposed to be associated with its rapid metabolism to dextrorphan, which restricts its central bioavailability and therapeutic utility. Systemic concentrations of DM can be increased via coadministration of low-dose quinidine (Q), which reversibly inhibits its first pass elimination. Potential drug interactions with DM/Q are discussed. CONCLUSIONS: Given the compelling preclinical evidence for neuroprotective properties of DM, initial clinical neuroprotective findings, and clinical demonstrations that the DM/Q combination is well tolerated, this strategy may hold promise for the treatment of various acute and degenerative neurologic disorders. PMID- 17848868 TI - Restless legs syndrome and periodic limb movements during sleep: diagnosis and treatment. AB - BACKGROUND: Restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS) have been known for over 300 years, and they may be present in as many as 25% of patients who have sleep disorders. These patients generally present with insomnia. These disorders often remain undiagnosed for an average of 16 years and patients have seen an average of 13 physicians for their symptoms. Therefore, these disorders merit the attention and interest of the practitioner, so that such patients can be evaluated and treated without delay. REVIEW SUMMARY: The important features of these disorders are the following: (1) their recognition since 1685, (2) they may comprise up to 25% of all sleep disorders, (3) they require differentiation from many other disorders, and (4) effective treatment is available. Although it is believed that RLS and PLMS are 2 clinical manifestations of the same central nervous system dysfunction, they are generally discussed separately, as different nosological entities. CONCLUSION: RLS and PLMS are common neurologic disorders and increase in prevalence with aging. These disorders can be disabling conditions, causing sleep disturbance at night and excessive sleepiness during the day. Polysomnography and the suggested immobilization test are used to support the clinical diagnosis of RLS and PLMS. Although levodopa alleviates symptoms, rebound and augmentation occur frequently, limiting the long-term usefulness of this agent. The direct dopamine receptor agonists such as pergolide, pramipexole, ropinirole, and cabergoline have largely replaced levodopa as the most effective treatment for RLS and PLMS. PMID- 17848869 TI - Progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): a short historical review. AB - J. C. Richardson presented a clinical report of 8 cases of progressive supranuclear palsy (PSP, progressive supranuclear palsy) in June 1963. This paper briefly reviews the clinical, neuropathologic, and genetic features that subsequently have evolved, emphasizing the difficulties of differential diagnosis. Since PSP appears to be a heterogeneous syndrome, its precise nosology remains uncertain. PMID- 17848870 TI - Angelman syndrome revisited. AB - OBJECTIVES: Angelman syndrome (AS) is characterized by severe mental retardation, epilepsy, absent speech, dysmorphic facial features, and a characteristic behavioral phenotype. It is caused by deficiency of gene expression from maternally derived chromosome 15q11-q13. STUDY DESIGN: The authors present the clinical picture of 9 children (median age, 4.9 years; range, 1 to 10 years) with confirmed Angelman syndrome. The patients complied with the international consensus criteria for AS and were consecutively investigated for psychomotor development, epilepsy, and electroencephalogram (EEG) profiles. RESULTS: The median age at diagnosis was 3.9 years. The motor milestones were delayed. Median developmental quotient level was 26. All patients but 1 experienced predominantly polymorphic seizures. In 4 cases, the epilepsy was refractory to treatment. The EEG of all patients displayed an abnormal sleep pattern and generalized abnormalities, with a maximum over the posterior areas. CONCLUSIONS: Milder or less typical phenotypes of AS may remain undiagnosed, leading to an overall underdiagnosis of the disease. The EEG shows no clear relation to genotype, clinical picture, or to the presence and severity of epilepsy. AS should be considered in the differential diagnosis of children with severe cryptogenic epilepsy and a characteristic configuration of clinical features. PMID- 17848871 TI - Segmental zoster paresis of limbs: report of three cases and review of literature. AB - OBJECTIVES: Segmental zoster paresis is a relatively rare complication characterized by focal motor weakness, which may occur in limbs affected by herpes zoster. We demonstrate the clinical characteristics of segmental zoster paresis by reviewing the cases of 138 patients, including 3 of our patients. CASE REPORT AND REVIEW SUMMARY: We report 3 patients with zoster paresis of the limbs. Patients 1 and 3 showed motor weakness in the left shoulder and arm after developing a herpetic rash in the left C5-C6 dermatomes. Patient 2 showed weakness in the right thigh and groin after a right L2-L3 herpetic eruption. The electromyograms of all 3 patients showed abnormal spontaneous activity in the affected muscles. Intravenous acyclovir and corticosteroid pulse therapy were added to oral antiviral drugs for patients 1 and 2. All 3 patients recovered favorably. Our review of the literature revealed that antiviral treatment may prevent the occurrence of zoster paresis; however, there is insufficient evidence to show what treatment hastens recovery from zoster paresis. CONCLUSIONS: Segmental zoster paresis is still underrecognized by neurologists. Awareness of this disorder is important because it may eliminate unnecessary invasive investigations and lead to appropriate treatment. Further studies on the treatment are necessary. PMID- 17848872 TI - 10 most commonly asked questions about carotid artery stent placement. PMID- 17848873 TI - Caffeine for the prevention and treatment of postdural puncture headache: debunking the myth. AB - OBJECTIVE: Is caffeine effective in preventing and treating postdural puncture headache (PDPH)? METHODS: The question was addressed with a structured evidence based clinical neurologic practice review via videoconferencing between 3 academic institutions. Participants included consultant and resident neurologists, clinical epidemiologists, medical librarians, and clinical content experts. A critically appraised topic format was employed, starting with a clinical scenario and structured question. Participant groups at each of the 3 institutions independently devised search strategies, located and compiled the best evidence, performed critical appraisals, synthesized the results, summarized the evidence, provided commentary, and declared bottom-line conclusions. RESULTS: Three directly relevant randomized controlled trial articles were selected as the best available evidence for the clinical questions. Two investigated caffeine [oral and intravenous (IV)] as PDPH prophylaxis and 1 (oral) as PDPH treatment. One additional quasirandomized trial (IV) and 1 open-label trial (IV) of caffeine for PDPH treatment were located by reviewing bibliographies. Articles describing the pharmacological basis for caffeine therapy were also identified. No valid pharmacological rationale for caffeine as an antinociceptive agent for PDPH exists. The clinical trials are few in number, small in sample size, methodologically weak or flawed, and either demonstrate no effectiveness, contradictory and conflicting results, or invalid answers. CONCLUSIONS: The wide endorsement for caffeine to prevent and treat PDPH found in textbooks and review articles appears to be unwarranted and insufficiently supported by the available pharmacological and clinical evidence. PMID- 17848874 TI - Patient and family fact sheet: Creutzfeldt-Jakob disease. PMID- 17848875 TI - Pneumococcal bacteremia among infants with fever without known source before and after introduction of pneumococcal conjugate vaccine in the Basque Country of Spain. AB - BACKGROUND: The introduction of vaccination with the heptavalent pneumococcal conjugate vaccine (PCV7) has produced an important decrease in the incidence of Streptococcus pneumoniae occult bacteremia (OB). In Spain, PCV7 became available in the last months of 2001, but, to date, it has not been included in the official vaccination schedule of the public health system. OBJECTIVE: To describe the impact of pneumococcal vaccination with PCV7 on the incidence of OB caused by S. pneumoniae in infants aged 3-36 months presenting to our pediatric emergency department. PATIENTS AND METHODS: This is a retrospective case series of all blood cultures obtained from January 1, 2000 to December 31, 2005 in our pediatric emergency department from infants with fever without known source. We evaluated rates of blood cultures positive with S. pneumoniae before (January 1, 2000-December 31, 2001) and after (January 1, 2004-December 31, 2005) PCV7 introduction, excluding 2 transitional years (January 1, 2002-December 31, 2003). RESULTS: Implementation of vaccination with PVC7 in our area resulted in a 57.5% reduction of OB caused by S. pneumoniae (1.62-0.69%) (P < 0.05). There were 30 cases of bacteremia caused by S. pneumoniae, 19 before and 11 after PCV7 introduction. Between the 2 periods of time studied the number of cases of infants aged 3-36 months with fever without known source, increased from 8052 to 9799 (21.6%) and the total blood cultures drawn significantly increased from 1171 to 1575 (34.5%) (P < 0.01). Despite more frequent blood culturing in febrile patients, the rate of OB caused by PCV7-serotypes decreased significantly by 79% (1.19-0.25%) (P < 0.01) and the proportion of OB caused by nonvaccine serotypes increased minimally from 0.42 to 0.44%. In the post-PVC7 period, 4 infants presented with S. pneumoniae OB caused by PCV7 serotypes; 2 had not received PCV7, and 2 (6 and 7 months old) had received one dose. CONCLUSION: After PCV7 introduction in our area, rates of S. pneumoniae OB caused by vaccine serotypes decreased significantly despite only moderate use of the vaccine in our population. PMID- 17848876 TI - Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial infections in febrile infants and children in the emergency department. AB - OBJECTIVE: To assess the value of procalcitonin (PCT) and C-reactive protein (CRP), compared with that of total white-blood cell count (WBC) and absolute neutrophil count (ANC), in predicting severe bacterial infections (SBIs) in febrile children admitted to Emergency Department. METHODS: A prospective study was conducted in 408 children aged 7-days to 36-months, admitted with fever without source, at a tertiary care Pediatric Emergency Department. PCT, CRP, WBC, and ANC were determined upon admission and compared. Specificity, sensitivity, multilevel likelihood ratios, receiver operating characteristic (ROC) analysis, and multivariate stepwise logistic regression were carried out. RESULTS: SBI was diagnosed in 94 children (23.1%). PCT, CRP, WBC, and ANC were significantly higher in this group than in non-SBI patients. The area under the ROC (AUC) obtained was 0.82 (95% CI: 0.78-0.86) for PCT, 0.85 (95% CI: 0.81-0.88) for CRP (P = 0.358), 0.71 (95% CI: 0.66-0.75) for WBC, and 0.74 (95% CI: 0.70-0.78) for ANC. Only PCT (OR: 1.32; 95% CI: 1.11-1.57; P < 0.001) and CRP (OR: 1.02; 95% CI: 1.01-1.03; P < 0.001) were retained as significant predictors of SBI in a multiple regression model. For infants with fever <8 hours (n = 45), AUC for PCT and CRP were 0.92 (95% CI: 0.80-0.98) and 0.75 (95% CI: 0.60-0.87), respectively (P = 0.056). CONCLUSION: Both PCT and CRP are valuable markers in predicting SBI in children with fever without source and they perform better than WBC and ANC. PCT appears more accurate at the beginning of infections, but overall CRP may be the most convenient marker for its better sensitivity and feasibility. PMID- 17848877 TI - Methicillin-resistant Staphylococcus aureus outbreak in an intensive care nursery: potential for interinstitutional spread. AB - BACKGROUND: After surveillance surveys documented the absence of methicillin resistant Staphylococcus aureus (MRSA) in our intensive care nursery, an outbreak of MRSA infection occurred there during a 7-month period in 2005. METHODS: Control measures included reinforcement of hand hygiene and contact precautions procedures. Active surveillance cultures were obtained on all neonates, including interinstitutional transfers. A cohort unit was dedicated exclusively for neonates with MRSA. Pulsed-field gel electrophoresis was performed on isolates to determine relatedness. We surveyed transferring hospitals to evaluate MRSA activity and surveillance practices in their nurseries. RESULTS: Twenty-five neonates were colonized with MRSA; 9 of these had clinical infections. Isolates from 18 of 21 neonates from this outbreak and 4 neonates from a previous cluster were identical, including 1 isolate obtained upon transfer from another institution. Admission and discharge logs from a 9-month period showed that 127 of 460 admissions (27.6%) were admitted from 34 hospitals, and 247 of 460 (53.7%) were discharged to 32 hospitals. Among 30 transferring hospitals responding to our survey, MRSA activity occurred in 2 of 28 (7%) level 1 nurseries, 4 of 11 (36%) level 2 nurseries and 6 of 10 (60%) level 3 nurseries. Nine of the 30 hospitals (30%) performed some active surveillance. CONCLUSIONS: Interinstitutional transfer can play a role in the initiation and propagation of MRSA outbreaks in neonatal nurseries. The burden of MRSA in area nurseries and the rate of transfers affect the potential for interhospital spread of MRSA and may justify changes in policy regarding surveillance for MRSA and communication between hospitals. PMID- 17848878 TI - Low plasma protein C values predict mortality in low birth weight neonates with septicemia. AB - BACKGROUND: Septicemia activates coagulation and decreases activated protein C (APC). Low APC in adults is associated with multiorgan dysfunction and mortality, but such data in neonates are lacking. Being deficient in APC, neonates may be especially vulnerable to the effects of low APC. METHODS: This cohort study was conducted on 40 neonates with severe bacterial septicemia to determine the relationship between plasma APC values and mortality, time to mortality, and hazard of dying. Low birth weight neonates with sepsis, organ dysfunction, and systemic inflammatory response syndrome were enrolled after parental consent. Plasma APC was assayed at enrollment and subjects were followed for 14 days from enrollment. Low birth weight neonates, who had major malformations, severe birth asphyxia, or received blood products before APC assay, were excluded. PRIMARY OUTCOME: comparison of APC level between survivors and nonsurvivors. SECONDARY OUTCOMES: survival with low versus normal APC; and hazard ratio of APC, adjusted for birth weight, Score for Neonatal Acute Physiology and number of affected organs. RESULTS: Forty of 74 eligible neonates were included. Twenty-five of the enrolled neonates died within 14 days. APC levels in nonsurvivors were lower than in survivors [median (interquartile range) %, 15 (4.5-21) versus 33 (18-55); P < 0.001]. Ten nonsurvivors versus 1 survivor had low APC (P = 0.03). Positive predictive value (PPV) of low APC values for mortality was 90.9%. Survival in the low APC group (n = 11) was shorter than in normal APC group [median (95% confidence interval) days, 3 (2.3-3.7) versus 10, P value <0.001]. APC value was independently associated with hazard of dying [adjusted risk 0.95 (95% confidence interval 0.92-0.99), P = 0.02]. Each 1% rise in APC decreased the hazard of dying by 5%. CONCLUSIONS: Mortality was higher and duration of survival shorter in septic neonates with lower plasma ACP. The latter was an independent predictor of the hazard of dying. PMID- 17848879 TI - The spectrum and management of otitis media in Australian indigenous and nonindigenous children: a national study. AB - BACKGROUND: Indigenous children have the highest reported prevalence and severity of otitis media in the world, but whether their clinical management varies accordingly is unknown. METHODS: Using a representative Australia-wide cluster survey of consecutive primary healthcare consultations, we compared practitioners' investigation, treatment, and referral practices for otitis media in indigenous and nonindigenous children (0-18 years), after adjusting for clustering. RESULTS: Over 8 years (1998-2006), 7991 practitioners managed 141,693 problems during 119,503 consultations with children, including 2856 (2%) with indigenous children. Ear problems were the fourth most common problems managed overall, with otitis media seen more commonly in indigenous than in nonindigenous children (10% versus 7% consultations, P < 0.001). Indigenous children were significantly more likely to have severe otitis media (chronic and/or suppurative and/or perforation, 8% versus 2%, P < 0.001); discharging ears (4% versus 0.1%, P < 0.001); ear swabs [4%, 95% confidence interval (CI): 2%-6% versus 0.8%, 95% CI: 0.6%-0.9%]; and topical eardrops administered (11%, 95% CI: 7%-15% versus 5%, 95% CI: 4%-5%); but not more likely to receive oral antibiotics (72% versus 76%); have ear syringing (1% versus 0.2%); be referred to an otolaryngologist (6% versus 3%) or audiologist (2% versus 1%); all P > 0.05. CONCLUSIONS: In the Australian primary healthcare setting, indigenous children are 5 times more likely to be diagnosed with severe otitis media than nonindigenous children, but reported management is not substantially different, which is inconsistent with established national guidelines. This spectrum-management discordance may contribute to continued worse outcomes for indigenous children with otitis media. PMID- 17848880 TI - Seasonality, incidence, and repeat human metapneumovirus lower respiratory tract infections in an area with a high prevalence of human immunodeficiency virus type 1 infection. AB - BACKGROUND: There is limited information regarding the epidemiology of human metapneumovirus (hMPV) from Africa, despite it being identified as a common pathogen in children with pneumonia. OBJECTIVES: Determine the epidemiology of severe hMPV-associated lower respiratory tract infection (LRTI) in human immunodeficiency virus type-1 (HIV) infected and uninfected children. METHODS: Nasopharyngeal aspirate samples from children hospitalized for LRTI between January 2000 and December 2002 were analyzed for common respiratory viruses using an immunofluorescence assay; and 2715 available nasopharyngeal aspirate samples were tested for hMPV by reverse-transcriptase polymerase chain reaction targeting its fusion protein. Phylogenetic analysis of the fusion (F) gene was performed on samples associated with repeat hMPV infections in the same child. RESULTS: hMPV was identified perennially and was the second most commonly identified respiratory virus (11.3% versus 21.1% for respiratory syncytial virus, P < 0.0001) in HIV-uninfected children. The burden of hospitalization for hMPV-LRTI was 5.4 (95% CI: 3.5-7.5) fold greater in HIV-infected (2935 per 100,000) compared with HIV-uninfected children [575 (95% CI: 472-695) per 100,000]. HIV infected children had greater evidence of bacterial coinfection and a higher mortality rate than did uninfected children. Repeat hMPV associated hospitalizations involved homologous (B2 subgroup) and heterologous (A1 and B2) hMPV. CONCLUSIONS: There is a high burden of hMPV-LRTI and repeat severe infections occur from homologous and heterologous subgroups of the virus. PMID- 17848881 TI - Herpes simplex virus in febrile neutropenic children undergoing chemotherapy for cancer: a prospective cohort study. AB - BACKGROUND: The primary objective of this study was to determine the prevalence of oral herpes simplex virus (HSV) as detected by polymerase chain reaction, in pediatric oncology patients with febrile neutropenia. Our secondary objectives were to describe the association between oral HSV and prolonged fever, neutropenia, mucositis, and response to initial antimicrobial therapy. METHODS: In this prospective cohort study, we obtained a mouth swab and blood specimen from oncology patients with febrile neutropenia, and tested them for HSV by polymerase chain reaction. Prolonged fever was defined as the presence of fever 48 hours after initiation of broad-spectrum antibiotic therapy. RESULTS: Of the 75 oral and blood specimens obtained, only 7 oral swabs (9%) and 2 blood samples (3%) were positive for HSV. Oral HSV was not associated with prolonged fever or neutropenia. However, oral HSV was associated with longer median duration of mucositis (8 days; interquartile range, 0-12 days) compared with negative episodes (0 days; interquartile range, 0-2.5 days); P = 0.005. Oral HSV also was associated with inferior successful response to initial antimicrobial therapy (1 of 7, 14.3%) compared with negative episodes (51 of 67, 76.1%); P = 0.002. CONCLUSIONS: The prevalence of HSV infection in pediatric oncology patients with febrile neutropenia was low and was not associated with prolonged fever. However, oral HSV was associated with prolonged mucositis and poorer response to initial therapy. It is unknown whether early intervention with acyclovir can alter these associations. PMID- 17848882 TI - Immunogenicity and safety of a pediatric dose of a virosome-adjuvanted hepatitis A vaccine: a controlled trial in children aged 1-16 years. AB - BACKGROUND: The availability of pediatric formulations of hepatitis A virus (HAV) vaccines would facilitate the introduction of universal mass vaccination against HAV. The objective of this study was to compare a pediatric dose (0.25 mL) of Epaxal, a virosomal, aluminum-free HAV vaccine, to 0.5 mL standard dose, and to alum-adsorbed HAV vaccine. METHODS: Subjects aged 1-16 years, stratified for age, were randomized (2:2:1) into group A (0.25 mL Epaxal), group B (0.5 mL Epaxal), or group C (Havrix Junior). Vaccines were administered at months 0, 6. Seroprotection rates (>or=10 mIU/mL anti-HAV antibodies) were assessed for noninferiority, defined as lower limit of 1-sided 97.5% CI >-10%. Incidence of local solicited adverse events and unsolicited adverse events were recorded. RESULTS: Mean age of 308 enrolled subjects was 8.9 years (range, 1.0-17.0 years). All 3 vaccines were highly immunogenic. Noninferiority of group A versus group B and group C with regard to seroprotection was demonstrated after both vaccine doses for the entire study group and for all age subgroups (11-23 months, 2-4, 5 7, 8-10, 11-13, 14-16 years). One month after first vaccination, geometric mean antibody concentrations were 69.0, 83.5, and 50.5 mIU/mL for the 3 groups, respectively (A versus B, P = 0.0208; A versus C, P = 0.0015). Local injection site pain occurred more frequently in group C than in groups A and B. No subjects withdrew from study or reported any vaccine-related serious adverse event. CONCLUSION: In children aged 1-16 years, 0.25 mL dose of Epaxal is as immunogenic as standard 0.5 mL dose and Havrix Junior. The aluminum-free vaccine compares favorably to comparator vaccine regarding local reactogenicity. PMID- 17848883 TI - Hepatitis A as an etiologic agent of acute liver failure in Latin America. AB - BACKGROUND: This prospective, multicenter study examined the importance of hepatitis viruses as etiological agents of acute liver failure (ALF) and the outcome of ALF cases in Latin American children and adolescents. METHODS: The study was conducted for minimum 12 months in 9 centers in Argentina, Brazil, Chile, Colombia, Costa Rica, and Mexico during 2001-2002. Hospitalized patients aged 1-20 years with a suspected diagnosis of ALF were included in the study and tested for serologic markers for hepatitis A, B, and C viruses. RESULTS: Of the 106 patients enrolled, 88 were included in the analysis. Median age was 5 years, and 55% with ALF were aged 1-5 years. A total of 37 individuals (43%) tested positive for anti-hepatitis A virus (HAV) immunoglobulin M (IgM) as marker of acute HAV infection; one was positive for anti-hepatitis B core antigen IgM and negative for hepatitis B surface antigen. None had markers of hepatitis C virus infection. Mortality rates in the overall study cohort (45%) and for those who tested anti-HAV IgM positive (41%) were similar. Forty-one percent of all patients and 46% of those positive for anti-HAV IgM underwent transplantation. The mortality rate in those with liver transplantation was half of that in patients who were not transplanted (28% versus 57%). CONCLUSIONS: HAV was the main etiologic agent of ALF in the population studied. PMID- 17848884 TI - Reconsideration of the use of meningococcal polysaccharide vaccine. AB - In 2005, a quadrivalent meningococcal conjugate vaccine was licensed in the United States for persons aged 11-55 years of age. For children aged 2-10 years with underlying diseases associated with increased risk of meningococcal disease, unconjugated meningococcal polysaccharide (MPS) vaccination is still recommended. This article reviews the increasing evidence that MPS vaccination impairs serum anticapsular antibody responses to subsequent injections of MPS or meningococcal conjugate vaccines (antibody hyporesponsiveness). Administering MPS as a probe to assess conjugate vaccine-induced immunologic memory also can extinguish subsequent memory anticapsular antibody responses, whereas conjugate vaccination regenerates memory B cells. Whether induction of antibody hyporesponsiveness or loss of immunologic memory increase the risk of acquiring meningococcal disease remains speculative. However, for children at increased risk of meningococcal disease, immunization with meningococcal quadrivalent conjugate vaccine off-label instead of MPS vaccine should be considered. Requirements for licensure of new glycoconjugate vaccines that include performing comparative clinical trials to demonstrate noninferiority with MPS vaccine, or use of a MPS challenge to assess conjugate-induced immunologic memory also should be modified because there are safer approaches for obtaining the same information. PMID- 17848885 TI - Zygomycosis in children: a systematic review and analysis of reported cases. AB - BACKGROUND: Zygomycosis has emerged as an increasingly important infection with a high mortality especially in immunocompromised patients. No comprehensive analysis of pediatric zygomycosis cases has been published to date. METHODS: We used a PUBMED search for English publications of pediatric (0-18 years) zygomycosis cases and references from major books as well as single case reports or case series. Individual references were reviewed for additional cases. Data were entered into Filemaker-pro database and analyzed by logistic regression analysis. RESULTS: One hundred fifty-seven cases (64% male) were found with median age 5 years (range, 0.16-13). Underlying conditions included neutropenia (18%), prematurity (17%), diabetes mellitus (15%), ketoacidosis (10%), and no apparent underlying condition (14%). The most common patterns of zygomycosis were cutaneous (27%), gastrointestinal (21%), rhinocerebral (18%), and pulmonary (16%). Among 77 culture-confirmed cases, Rhizopus spp. (44%) and Mucor spp. (15%) were most commonly identified. Of 81 patients who were given antifungal therapy, 73% received an amphotericin B formulation only. The remaining patients received mostly amphotericin B in combination with other antifungal agents. Mortality in patients without antifungal therapy was higher than in those with therapy (88% versus 36%, P < 0.0001). Ninety-two (59%) patients underwent surgery. Cerebral, gastrointestinal, disseminated and cutaneous zygomycosis were associated with mortality rates of 100, 100, 88, and 0%, respectively. Independent risk factors for death were disseminated infection (OR: 7.18; 95% CI: 3.02-36.59) and age <1 year (OR: 3.85; 95% CI: 1.05-7.43). Antifungal therapy and particularly surgery reduced risk of death by 92% (OR: 0.07; 95% CI: 0.04-0.25) and 84% (OR: 0.16; 95% CI: 0.09-0.61), respectively. CONCLUSIONS: Zygomycosis is a life-threatening infection in children with neutropenia, diabetes mellitus, and prematurity as common predisposing factors, and there is high mortality in untreated disease, disseminated infection, and age <1 year. Amphotericin B and surgery significantly improve outcome. PMID- 17848886 TI - Guidelines for diagnosis and management of aphthous stomatitis. AB - Aphthous ulcers are the most common oral mucosal lesions in the general population. These often are recurrent and periodic lesions that cause clinically significant morbidity. Many suggestions have been proposed but the etiology of recurrent aphthous stomatitis (RAS) is unknown. Several precipitating factors for aphthous ulcers appear to operate in subjects with genetic predisposition. An autoimmune or hypersensitivity mechanism is widely considered possible. Sometimes aphthous ulcers can be the sign of systemic diseases, so it is essential to establish a correct diagnosis to determine suitable therapy. Before initiating medications for aphthous lesions, clinicians should determine whether well recognized causes are contributing to the disease and these factors should be corrected. Various treatment modalities are used, but no therapy is definitive. Topical medications, such as antimicrobial mouth-washes and topical corticosteroids (dexamethasone, triamcinolone, fluocinonide, or clobetasol), can achieve the primary goal to reduce pain and to improve healing time but do not improve recurrence or remission rates. Systemic medications can be tried if topical therapy is ineffective. PMID- 17848887 TI - The association between respiratory syncytial virus infection and the development of childhood asthma: a systematic review of the literature. AB - BACKGROUND: The relation between early respiratory syncytial virus (RSV) infection and later emergence of episodes of wheezing/asthma remains a subject of debate. We carried out a systematic review of studies of the association between RSV infection in the first 36 months of life and the subsequent development of asthma/bronchial hyperreactivity. METHODS: A literature search for original studies on RSV respiratory infection published in English or Spanish over the last 21 years was conducted in the bibliographic databases Medline, Embase, and Indice Medico Espanol, and in the Cochrane library. Articles were included if they described original studies of confirmed RSV infection in children under 3 years of age, and had defined outcome variables. The methodologic quality of articles included in the review was evaluated according to the Hadorn criteria. RESULTS: The review included 12 original articles that respond to the research question. The studies evaluated showed that RSV lower respiratory tract infection is associated with an increased risk for subsequent development of asthma/recurrent wheezing, and that this association becomes progressively smaller with increasing age. CONCLUSION: On the basis of this systematic review of the literature, it can be concluded that a significant association exists between RSV infection in childhood and the long-term development of subsequent episodes of recurrent wheezing or asthma. However, the methodologic quality of the articles evaluated is limited, and hence additional studies are needed, ideally, with specific therapeutic interventions aimed at reducing RSV replication. PMID- 17848888 TI - ORF virus infection in children: clinical characteristics, transmission, diagnostic methods, and future therapeutics. AB - Orf virus leads to self-limited, subacute cutaneous infections in children who have occupational or recreational contact with infected small ruminants. Breaches in the integument and contact with animals recently vaccinated for orf may be important risk factors in transmission. Common childhood behaviors are likely important factors in the provocation of significant contact (ie, bites) or in unusual lesion location (eg, facial lesions). Clinician recognition is important in distinguishing orf infection from life-threatening cutaneous zoonoses. Recently developed molecular techniques provide diagnostic precision and newer topical therapeutics may hasten healing. PMID- 17848889 TI - Newly identified respiratory viruses. PMID- 17848890 TI - Changing epidemiology and prevention of Salmonella infections. PMID- 17848891 TI - Distribution of serum measles-neutralizing antibodies according to age in women of childbearing age in France in 2005-2006: impact of routine immunization. AB - Measles antibody titers were measured in 210 French women. Ninety-four percent had protective values (>120 mIU/mL). Geometric mean titers were significantly different (P < 0.001) between women born before and after 1983, when measles vaccination was recommended (731 and 1358 mIU/mL, respectively). geometric mean titers in 4 age cohorts decreased significantly (P < 0.001) with increasing birth year. These data may help identify the appropriate age for infant vaccination. PMID- 17848892 TI - The characterization of cerebrospinal fluid and serum cytokines in patients with Kawasaki disease. AB - BACKGROUND: The central nervous system (CNS) inflammation of Kawasaki disease (KD) has not been sufficiently evaluated in spite of the complications of irritability and CSF pleocytosis. PATIENTS AND METHODS: Cerebrospinal fluid (CSF) and serum inflammatory cytokine values were simultaneously examined in 10 patients (2.6 +/- 2.1 year of age) during the acute phase. They were all irritable and demonstrated mild consciousness disturbance. RESULTS: The CSF IL6 was elevated (>3.0 pg/mL) in 6 patients, and 4 of them showed higher CSF than serum values. The CSF sTNFR1 was elevated (>0.5 microg/mL) in 6 patients, and 1 showed higher CSF than serum values. These CSF cytokine (IL6; 81.4 +/- 192.8 pg/mL, sTNFR1; 1.1 +/- 0.8 microg/mL) and CSF/serum ratio (IL6; 2.8 +/- 5.2, sTNFR1 0.4 +/- 0.4) in patients with KD were the same as those of patients with acute encephalitis/acute encephalopathy. CONCLUSIONS: The differences in the inflammatory cytokine value between CSF and serum suggest that the degree of systemic vasculitis is different between CSF and the circulating blood, and some patients with KD showed a higher degree of CSF inflammation. PMID- 17848893 TI - Coronavirus-associated pneumonia in previously healthy children. AB - The extent to which coronaviruses are associated with lower respiratory tract disease in previously healthy children without underlying medical conditions is unknown. We investigated instances of radiographically confirmed lower respiratory tract disease among symptomatic children with coronavirus infection. Here, we document the clinical courses of 2 previously healthy children with coronavirus-associated pneumonia. PMID- 17848894 TI - Cutaneous Mycobacterium avium complex infection as a manifestation of the immune reconstitution syndrome in a human immunodeficiency virus-infected child. AB - We report a 13-year-old boy with human immunodeficiency virus infection who developed cutaneous Mycobacterium avium complex infection 2 months after commencing highly active antiretroviral therapy. The case illustrates that cutaneous Mycobacterium avium complex may present as a manifestation of the immune reconstitution syndrome in human immunodeficiency virus-infected children. PMID- 17848895 TI - Infected subgaleal hematoma in a neonate. AB - Subgaleal hematoma (SGH) is an infrequent finding in neonates, occurring mostly after vacuum extraction deliveries. SGH can cause anemia, hypovolemic shock, and death. To date, only one case of neonatal infected SGH has previously been reported. We describe a term neonate with severe polymicrobial infection complicating SGH, including anaerobic bacteria, and with unique imaging features. PMID- 17848896 TI - Toxic shock syndrome in a neonate. AB - We report an unusual case of toxic shock syndrome in a 4-day-old baby, with mucosal isolates of Staphylococcus aureus (SEC, G, and I) and group G streptococcus. Treatment involved intravenous immunoglobulin and antibiotics. This case highlights the difficulties associated with the diagnosis and treatment of this condition in neonates. PMID- 17848897 TI - Legionella bozemanii pulmonary abscess in a pediatric allogeneic stem cell transplant recipient. AB - Legionella spp. infections are often considered in the differential diagnosis of pneumonia in adults. This case report describes a pediatric stem cell transplant recipient presenting with cavitary pulmonary disease secondary to Legionella bozemanii infection. Also highlighted with this atypical clinical presentation are challenges in diagnosing legionellosis and concerns of increased vulnerability for such infections when severely immunocompromised patients are changed to nontrimethoprim-sulfamethoxazole Pneumocystis jiroveci pneumonia prophylaxis. PMID- 17848898 TI - Persistent hepatitis and repeated wheezing in an infant. Q fever. PMID- 17848899 TI - Erythema nodosum, Mycobacterium avium lymphadenitis, and a 15-mm Mantoux test. PMID- 17848900 TI - Perinephric abscess caused by community-acquired methicillin resistant Staphylococcus aureus. PMID- 17848902 TI - Respiratory distress related to asymptomatic colonization with group B streptococci. PMID- 17848903 TI - Fulminant hepatic failure following measles. PMID- 17848904 TI - West Nile virus cerebellitis in a healthy 10-year-old child. PMID- 17848905 TI - Tinidazole (Tindamax)--a new option for treatment of bacterial vaginosis. PMID- 17848906 TI - Lapatinib (Tykerb) for advanced breast cancer. PMID- 17848907 TI - Removable permanent tattoo ink. PMID- 17848908 TI - A randomised controlled study of an audiovisual patient information intervention on informed consent and recruitment to cancer clinical trials. AB - Recruitment to cancer clinical trials needs to be improved, as does patient knowledge and understanding about clinical trials, in order for patients to make an informed choice about whether or not to take part. Audiovisual patient information (AVPI) has been shown to improve knowledge and understanding in various areas of practice, but there is limited information about its effect in the cancer clinical trial setting, particularly in relation to consent rates. In this study, 173 patients were randomised to receive either the AVPI, in addition to the standard trial-specific written information, or the written information alone. There was no difference in clinical trial recruitment rates between the two groups with similar study entry rates: 72.1% in the AVPI group and 75.9% in the standard information group. The estimated odds ratio for refusal (intervention/no intervention) was 1.19 (95% CI 0.55-2.58, P=0.661). Knowledge scores increased more in the AVPI group compared to the standard group (P=0.0072). The change in anxiety score between the arms was also statistically significant (P=0.011) with anxiety improving in the intervention arm more than in the no intervention arm. Audiovisual patient information was shown to be a useful tool in improving patient knowledge and anxiety, but further work is necessary in relation to its effect on clinical trial recruitment rates. PMID- 17848909 TI - Postoperative chemoradiotherapy in gastric cancer -- a Phase I/II dose-finding study of radiotherapy with dose escalation of cisplatin and capecitabine chemotherapy. AB - We hypothesised that gastric cancer outcome could be improved with more effective and intensified postoperative chemoradiotherapy. This phase I/II study was performed to determine the maximal tolerated dose (MTD) and toxicity profile of postoperative radiotherapy with concurrent daily cisplatin and capecitabine. Patients were treated with capecitabine 1000 mg m(-2) twice a day (b.i.d.) for 2 weeks. Subsequently, patients received capecitabine (250-650 mg m(-2) orally b.i.d., 5 days week(-1)) and cisplatin (3-6 mg m(-2) i.v., 5 days week(-1)) according to an alternating dose-escalation schedule. Radiotherapy was given to a total dose of 45 Gy in 25 fractions. Thirty-one patients completed treatment. During chemoradiotherapy, eight patients developed nine items of grade III and one episode of grade IV (mainly haematological) toxicity. The MTD was determined to be cisplatin 5 mg m(-2) i.v. and capecitabine 650 mg m(-2) b.i.d. orally. This phase I/II study demonstrated that chemoradiotherapy with daily cisplatin and capecitabine is feasible in postoperative gastric cancer at the defined dose level and is currently being tested in a phase III multicenter study. PMID- 17848910 TI - Benefit from preoperative radiotherapy in rectal cancer treatment: disease-free patients' and oncologists' preferences. AB - Preoperative radiotherapy (PRT) in resectable rectal cancer improves local control but increases probability of faecal incontinence and sexual dysfunction. Consensus was reached in 2001 in the Netherlands on a guideline advising PRT to new patients. Purpose was to assess at what benefit oncologists and rectal cancer patients prefer PRT followed by surgery to surgery alone, and how oncologists and patients value various treatment outcomes. Sixty-six disease-free patients and 60 oncologists (surgical, radiation, medical) were interviewed. Minimally desired benefit from PRT (local control) was assessed using the Treatment Tradeoff Method. Importance of survival, local control, faecal incontinence, and sexual dysfunction in determining treatment outcome preferences was assessed using Adaptive Conjoint Analysis. The range of required benefit from PRT varied widely within participant groups. Seventeen percent of patients would choose PRT at a 0% benefit; 11% would not choose PRT for the maximum benefit of 11%. Mean minimally desired benefit excluding these two groups was 4%. For oncologists, the required benefit was 5%. Also, how strongly participants valued treatment outcomes varied widely within groups. Of the four outcomes, participants considered incontinence most often as most important. Relative treatment outcome importance differed between specialties. Patients considered sexual functioning more important than oncologists. Large differences in treatment preferences exist between individual patients and oncologists. Oncologists should adequately inform their patients about the risks and benefits of PRT, and elicit patient preferences regarding treatment outcomes. PMID- 17848911 TI - Radiotherapy following breast-conserving surgery for screen-detected ductal carcinoma in situ: indications and utilisation in the UK. Interim findings from the Sloane Project. AB - Use of radiotherapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) varies according to country, precedent and prejudice. Results from a preliminary analysis of the data available within the UK Sloane Project can be appreciated in the context of the uncertainty concerning the selection of adjuvant RT following BCS for DCIS. There was a marked geographical variation in the use of RT within the United Kingdom. However, overall, patients with DCIS treated with BCS were significantly more likely to have RT planned (and given) if they had large (> or =15 mm), intermediate or high-grade tumours or if central comedo-type necrosis was present. Unexpectedly, margin width did not appear to have a significant effect on the decision-making process. However, the Van Nuys Prognostic Index did significantly affect the chances of getting planned RT in the univariate analysis, suggesting that clinicians may be starting to use this scoring system in routine practice to assist in decision making. PMID- 17848912 TI - Evaluation of epidermal growth factor receptor mutation status in serum DNA as a predictor of response to gefitinib (IRESSA). AB - The aim of this study was to evaluate the usefulness of EGFR mutation status in serum DNA as a means of predicting a benefit from gefitinib (IRESSA) therapy in Japanese patients with non-small cell lung cancer (NSCLC). We obtained pairs of tumour and serum samples from 42 patients treated with gefitinib. EGFR mutation status was determined by a direct sequencing method and by Scorpion Amplification Refractory Mutation System (ARMS) technology. EGFR mutations were detected in the tumour samples of eight patients and in the serum samples of seven patients. EGFR mutation status in the tumours and serum samples was consistent in 39 (92.9%) of the 42 pairs. EGFR mutations were strong correlations between both EGFR mutation status in the tumour samples and serum samples and objective response to gefitinib (P<0.001). Median progression-free survival time was significantly longer in the patients with EGFR mutations than in the patients without EGFR mutations (194 vs 55 days, P=0.016, in tumour samples; 174 vs 58 days, P=0.044, in serum samples). The results suggest that it is feasible to use serum DNA to detect EGFR mutation, and that it's potential as a predictor of response to, and survival on gefitinib is worthy of further evaluation. PMID- 17848913 TI - PDK-1/AKT pathway as a novel therapeutic target in rhabdomyosarcoma cells using OSU-03012 compound. AB - Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma including two major subtypes, alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS). Increasing evidence suggests that oncogenesis of RMS involves multiple stages of signalling protein dysregulation which may include prolonged activation of serine/threonine kinases such as phosphoinositide dependent kinase-1 (PDK-1) and AKT. To date, whether PDK-1/AKT pathway is activated in RMS is unknown. This study was to examine phosphorylation status of AKT and to evaluate a novel small molecular inhibitor, OSU-03012 targeting PDK-1 in RMS. We examined phosphorylation levels of AKT using ARMS and ERMS tissue microarray and immunohistochemistry staining. Our results showed phospho AKT(Thr308) level is elevated 42 and 35% in ARMS and ERMS, respectively. Phospho AKT(Ser473) level is also increased 43% in ARMS and 55% in ERMS. Furthermore, we showed that OSU-03012 inhibits cell viability and induces apoptosis in ARMS and ERMS cell lines (RH30, SMS-CTR), which express elevated phospho-AKT levels. Normal cells are much less sensitive to OSU-03012 and in which no detectable apoptosis was observed. This study showed, for the first time, that PDK-1/AKT pathway is activated in RMS and may play an important role in survival of RMS. PDK-1/AKT pathway may be an attractive therapeutic target for cancer intervention in RMS using OSU-03012. PMID- 17848915 TI - Advances in behavioral genetics: mouse models of autism. AB - Autism is a neurodevelopmental syndrome with markedly high heritability. The diagnostic indicators of autism are core behavioral symptoms, rather than definitive neuropathological markers. Etiology is thought to involve complex, multigenic interactions and possible environmental contributions. In this review, we focus on genetic pathways with multiple members represented in autism candidate gene lists. Many of these pathways can also be impinged upon by environmental risk factors associated with the disorder. The mouse model system provides a method to experimentally manipulate candidate genes for autism susceptibility, and to use environmental challenges to drive aberrant gene expression and cell pathology early in development. Mouse models for fragile X syndrome, Rett syndrome and other disorders associated with autistic-like behavior have elucidated neuropathology that might underlie the autism phenotype, including abnormalities in synaptic plasticity. Mouse models have also been used to investigate the effects of alterations in signaling pathways on neuronal migration, neurotransmission and brain anatomy, relevant to findings in autistic populations. Advances have included the evaluation of mouse models with behavioral assays designed to reflect disease symptoms, including impaired social interaction, communication deficits and repetitive behaviors, and the symptom onset during the neonatal period. Research focusing on the effect of gene-by-gene interactions or genetic susceptibility to detrimental environmental challenges may further understanding of the complex etiology for autism. PMID- 17848914 TI - Genetic variation in five genes important in telomere biology and risk for breast cancer. AB - Telomeres, consisting of TTAGGG nucleotide repeats and a protein complex at chromosome ends, are critical for maintaining chromosomal stability. Genomic instability, following telomere crisis, may contribute to breast cancer pathogenesis. Many genes critical in telomere biology have limited nucleotide diversity, thus, single nucleotide polymorphisms (SNPs) in this pathway could contribute to breast cancer risk. In a population-based study of 1995 breast cancer cases and 2296 controls from Poland, 24 SNPs representing common variation in POT1, TEP1, TERF1, TERF2 and TERT were genotyped. We did not identify any significant associations between individual SNPs or haplotypes and breast cancer risk; however, data suggested that three correlated SNPs in TERT (-1381C>T, 244C>T, and Ex2-659G>A) may be associated with reduced risk of breast cancer among individuals with a family history of breast cancer (odds ratios 0.73, 0.66, and 0.57, 95% confidence intervals 0.53-1.00, 0.46-0.95 and 0.39-0.84, respectively). In conclusion, our data do not support substantial overall associations between SNPs in telomere pathway genes and breast cancer risk. Intriguing associations with variants in TERT among women with a family history of breast cancer warrant follow-up in independent studies. PMID- 17848916 TI - Increased serotonin 2C receptor mRNA editing: a possible risk factor for suicide. AB - Suicide is a major public health problem with approximately 1 million victims each year worldwide. Up to 90% of adults who commit suicide have at least one psychiatric diagnosis such as major depression, bipolar disorder (BPD), schizophrenia (SZ), substance abuse or dependence. A question that has remained unanswered is whether the biological substrates of suicide are distinct from those of the psychiatric disorders in which it occurs. The serotonin 2C receptor (5-HT 2C R) has been implicated in depression and suicide. We, therefore, compared the frequencies of its mRNA editing variants in postmortem prefrontal cortical specimens from subjects who committed suicide or who died from other causes. All suicides occurred in the context of either SZ or BPD. The non-suicide cases included subjects with either SZ or BPD as well as subjects with no psychiatric diagnosis. We identified 5-HT 2CR mRNA editing variations that were associated with suicide but not with the comorbid psychiatric diagnoses, and were not influenced by demographic characteristics (age and sex) and alcohol or drug use. These variations consisted of a significant increase in the pool of mRNA variants (ACD and ABCD) that encode one of the most prevalent and highly edited isoforms of 5-HT 2C R, that is, VSV (Val156-Ser158-Val160). Because the VSV isoform of 5-HT 2C R exhibits low functional activity, an increase in its expression frequency may significantly influence the serotonergic regulation of the brain. Thus, at least in patients with SZ or BPD, overexpression of the VSV isoform in the prefrontal cortex may represent an additional risk factor for suicidal behavior. PMID- 17848917 TI - Inducible expression of mutant human DISC1 in mice is associated with brain and behavioral abnormalities reminiscent of schizophrenia. AB - A strong candidate gene for schizophrenia and major mental disorders, disrupted in-schizophrenia 1 (DISC1) was first described in a large Scottish family in which a balanced chromosomal translocation segregates with schizophrenia and other psychiatric illnesses. The translocation mutation may result in loss of DISC1 function via haploinsufficiency or dominant-negative effects of a predicted mutant DISC1 truncated protein product. DISC1 has been implicated in neurodevelopment, including maturation of the cerebral cortex. To evaluate the neuronal and behavioral effects of mutant DISC1, the Tet-off system under the regulation of the CAMKII promoter was used to generate transgenic mice with inducible expression of mutant human DISC1 (hDISC1) limited to forebrain regions, including cerebral cortex, hippocampus and striatum. Expression of mutant hDISC1 was not associated with gross neurodevelopmental abnormalities, but led to a mild enlargement of the lateral ventricles and attenuation of neurite outgrowth in primary cortical neurons. These morphological changes were associated with decreased protein levels of endogenous mouse DISC1, LIS1 and SNAP-25. Compared to their sex-matched littermate controls, mutant hDISC1 transgenic male mice exhibited spontaneous hyperactivity in the open field and alterations in social interaction, and transgenic female mice showed deficient spatial memory. The results show that the neuronal and behavioral effects of mutant hDISC1 are consistent with a dominant-negative mechanism, and are similar to some features of schizophrenia. The present mouse model may facilitate the study of aspects of the pathogenesis of schizophrenia. PMID- 17848918 TI - Central actions of liver-derived insulin-like growth factor I underlying its pro cognitive effects. AB - Increasing evidence indicates that circulating insulin-like growth factor I (IGF I) acts as a peripheral neuroactive signal participating not only in protection against injury but also in normal brain function. Epidemiological studies in humans as well as recent evidence in experimental animals suggest that blood borne IGF-I may be involved in cognitive performance. In agreement with observations in humans, we found that mice with low-serum IGF-I levels due to liver-specific targeted disruption of the IGF-I gene presented cognitive deficits, as evidenced by impaired performance in a hippocampal-dependent spatial recognition task. Mice with serum IGF-I deficiency also have disrupted long-term potentiation (LTP) in the hippocampus, but not in cortex. Impaired hippocampal LTP was associated with a reduction in the density of glutamatergic boutons that led to an imbalance in the glutamatergic/GABAergic synapse ratio in this brain area. Behavioral and synaptic deficits were ameliorated in serum IGF-I-deficient mice by prolonged systemic administration of IGF-I that normalized the density of glutamatergic boutons in the hippocampus. Altogether these results indicate that liver-derived circulating IGF-I affects crucial aspects of mature brain function; that is, learning and synaptic plasticity, through its trophic effects on central glutamatergic synapses. Declining levels of serum IGF-I during aging may therefore contribute to age-associated cognitive loss. PMID- 17848919 TI - Atypical antipsychotic-induced metabolic side effects: insights from receptor binding profiles. AB - Atypical antipsychotic drugs offer several notable benefits over typical antipsychotics, including greater improvement in negative symptoms, cognitive function, prevention of deterioration, and quality of life, and fewer extrapyramidal symptoms (EPS). However, concerns about EPS have been replaced by concerns about other side effects, such as weight gain, glucose dysregulation and dyslipidemia. These side effects are associated with potential long-term cardiovascular health risks, decreased medication adherence, and may eventually lead to clinical deterioration. Despite a greater understanding of the biochemical effects of these drugs in recent years, the pharmacological mechanisms underlying their various therapeutic properties and related side effects remain unclear. Besides dopamine D(2) receptor antagonism, a characteristic feature of all atypical antipsychotic drugs, these agents also bind to a range of non-dopaminergic targets, including serotonin, glutamate, histamine, alpha-adrenergic and muscarinic receptors. This review examines the potential contribution of different receptors to metabolic side effects associated with atypical antipsychotic treatment for all seven agents currently marketed in the United States (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone and clozapine) and another agent (bifeprunox) in clinical development at the time of this publication. PMID- 17848920 TI - Long-term outcomes and cost-effectiveness of screening for abdominal aortic aneurysm. PMID- 17848921 TI - Evaluating strategies for behavior change to reduce cardiovascular risk. PMID- 17848922 TI - Is hyperhomocysteinemia associated with osteoporosis in patients with Crohn's disease? PMID- 17848923 TI - Does the presence of hepatic steatosis influence the efficacy of antiviral treatment in patients with hepatitis C? PMID- 17848924 TI - Is surgery more effective than medical therapy for long-term symptom control in patients with reflux esophagitis? PMID- 17848925 TI - Diabetic ketoacidosis in type 2 diabetes mellitus--pathophysiology and clinical presentation. PMID- 17848926 TI - Does treatment with rosiglitazone increase cardiovascular risk of patients with type 2 diabetes mellitus? PMID- 17848927 TI - A total ischemia time of >24 h does not preclude transplantation of kidneys from non-heartbeating donors. PMID- 17848928 TI - Is angiotensin-converting-enzyme inhibition renoprotective in young patients with IgA nephropathy? PMID- 17848929 TI - Sumatriptan-naproxen combination for acute migraine. PMID- 17848930 TI - Prevention of venous thromboembolism in patients with stroke--enoxaparin vs unfractionated heparin. PMID- 17848931 TI - Aromatase inhibitors and tamoxifen: where do we go from here? PMID- 17848932 TI - Stereotactic radiotherapy for stage I non-small-cell lung cancer--the triumph of technology over biology? PMID- 17848933 TI - Possible implication of the effector CD4+ T-cell subpopulation TH17 in the pathogenesis of systemic scleroderma. PMID- 17848934 TI - Is genitourinary imaging necessary in patients who have microscopic hematuria after trauma? PMID- 17848935 TI - Should frozen section examination of the ureteral margins be routinely performed during cystectomy? PMID- 17848936 TI - Obese men respond to cognitive but not to catabolic brain insulin signaling. AB - CONTEXT AND OBJECTIVE: Insulin acts in the brain to reduce food intake and body weight and is considered a major adiposity signal in energy homeostasis. In normal-weight men, intranasal insulin administration reduces body fat and improves declarative memory. The present experiments aimed to generalize these findings to obese patients, with a view to evaluate the therapeutic potential of the compound. DESIGN, SUBJECTS AND MEASUREMENTS: Insulin and placebo, respectively, were intranasally administered four times a day (amounting to 160 IU day(-1)) over 8 weeks to two groups of 15 obese men each. RESULTS: Contrasting with the catabolic effects in normal-weight men, insulin treatment did not induce any significant reduction of body weight (P>0.50) and body fat (P>0.44) in the obese subjects. However, in accordance with the effects in normal-weight men, declarative memory and mood were improved (P<0.05) and hypothalamic-pituitary adrenal axis activity as assessed by circulating ACTH (P<0.01) and cortisol levels (P<0.04) was reduced. CONCLUSIONS: Our results indicate that in obese men, intranasal insulin is functionally active in the central nervous system but fails to affect the neuronal networks critically involved in body weight regulation. We conclude that obesity in men is associated with central nervous resistance to the adiposity signal insulin. This defect likely contributes to the persistence of obesity in spite of elevated levels of circulating insulin in obese patients. PMID- 17848937 TI - Nine-year incidence of obesity and overweight in an African-origin population. AB - OBJECTIVE: To provide 9-year incidence estimates for obesity and overweight and describe weight changes over time in an African-origin population. DESIGN: A population-based cohort in which participants were examined at baseline and reexamined after 9 years. MEASUREMENTS: Obesity and overweight were defined as having body mass indices (BMIs)> or =30 and 25 kg m(-2), respectively. Incidence rates were based on persons without such conditions at baseline and are presented along with 95% confidence intervals. RESULTS: Of the 869 men and 921 women at risk at baseline, the 9-year gender-specific incidence rates for obesity were 6.9% (95% confidence interval (5.3, 8.8)) and 13.1% (11.0, 15.5), respectively. The incidence of obesity steadily declined with age, decreasing from 14.4% for those between 40 and 49 years of age to 1.5% for those who were 70 years and older. Overall, the incidence of obesity over 9 years was approximately 10%. The 9-year incidence rate for overweight was 23.3% (20.5, 26.3). Changes in weight over the 9-year period varied by age group. Persons 40-49 years of age at baseline gained, on average, almost 3% of their baseline body weight, whereas persons > or =70 years lost 5% of their body weight in 9 years. CONCLUSIONS: This study highlights the high incidence of obesity/overweight in this cohort and suggests that the future public health burden of excess weight and its associated comorbidities may be elevated in this population of African origin. The development of strategies and interventions for the prevention and treatment of obesity/overweight are therefore of primary and immediate importance. PMID- 17848938 TI - What is the required energy deficit per unit weight loss? AB - One of the most pervasive weight loss rules is that a cumulative energy deficit of 3500 kcal is required per pound of body weight loss, or equivalently 32.2 MJ kg(-1). Under what conditions is it appropriate to use this rule of thumb and what are the factors that determine the cumulative energy deficit required per unit weight loss? Here, I examine this question using a modification of the classic Forbes equation that predicts the composition of weight loss as a function of the initial body fat and magnitude of weight loss. The resulting model predicts that a larger cumulative energy deficit is required per unit weight loss for people with greater initial body fat-a prediction supported by published weight loss data from obese and lean subjects. This may also explain why men can lose more weight than women for a given energy deficit since women typically have more body fat than men of similar body weight. Furthermore, additional weight loss is predicted to be associated with a lower average cumulative energy deficit since a greater proportion of the weight loss is predicted to result from loss of lean body mass, which has a relatively low energy density in comparison with body fat. The rule of thumb approximately matches the predicted energy density of lost weight in obese subjects with an initial body fat above 30 kg but overestimates the cumulative energy deficit required per unit weight loss for people with lower initial body fat. International Journal of Obesity (2008) 32, 573-576; doi:10.1038/sj.ijo.0803720; published online 11 September 2007. PMID- 17848939 TI - Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study. AB - OBJECTIVE: Lifestyle and genetic factors interact in the development of obesity and the metabolic syndrome. The molecular mechanisms underlying the beneficial dietary modifications are, however, unclear. We aimed to examine the effect of the long-term moderate weight reduction on gene expression in adipose tissue (AT) and to identify genes and gene clusters responsive to treatment and thereby likely contributing to the development of the metabolic syndrome. DESIGN: Randomized controlled and individualized weight reduction intervention. SUBJECTS: Forty-six subjects with impaired fasting glycemia or impaired glucose tolerance and features of metabolic syndrome, aged 60+/-7 years were randomized either to a weight reduction (WR) (n=28) or a control (n=18) group lasting for 33 weeks. MEASUREMENTS: Oral and intravenous glucose tolerance tests and subcutaneous AT biopsies were performed before and after the intervention. Gene expression of AT was studied using microarray technology in subgroups of WR (with weight reduction > or =5%, n=9) and control group (n=10). The results were confirmed using quantitative PCR. RESULTS: In the WR group, glucose metabolism improved. Moreover, an inverse correlation between the change in S (I) and the change in body weight was found (r=-0.44, P=0.026). Downregulation of gene expression (P<0.01) involving gene ontology groups of extracellular matrix and cell death was seen. Such changes did not occur in the control group. The tenomodulin-gene was one of the most downregulated genes (-39+/-16%, P<0.0001). Moreover, its expression correlated with insulin sensitivity (r=-0.34, P=0.005) before the intervention and with body adiposity both before (r=0.42, P=0.007) and after (r=0.30, P=0.056) the intervention. CONCLUSION: Genes regulating the extracellular matrix and cell death showed a strong downregulation after long term weight reduction. This likely reflects a new stable state at the molecular level in AT. Further studies are warranted to elucidate the mechanisms of these genetic factors. PMID- 17848940 TI - The impact of obesity on the musculoskeletal system. AB - Obesity is associated with a range of disabling musculoskeletal conditions in adults. As the prevalence of obesity increases, the societal burden of these chronic musculoskeletal conditions, in terms of disability, health-related quality of life, and health-care costs, also increases. Research exploring the nature and strength of the associations between obesity and musculoskeletal conditions is accumulating, providing a better understanding of underlying mechanisms. Weight reduction is important in ameliorating some of the manifestations of musculoskeletal disease and improving function. PMID- 17848941 TI - Individual variability following 12 weeks of supervised exercise: identification and characterization of compensation for exercise-induced weight loss. AB - OBJECTIVE: To identify and characterize the individual variability in compensation for exercise-induced changes in energy expenditure (EE). DESIGN: Twelve-week exercise intervention. SUBJECTS: Thirty-five overweight and obese sedentary men and women (body mass index, 31.8+/-4.1 kg m(-2); age, 39.6+/-11.0 years) were prescribed exercise five times per week for 12 weeks under supervised conditions. MEASUREMENTS: Body weight, body composition, resting metabolic rate (RMR), total daily energy intake (EI) and subjective appetite sensations were measured at weeks 0 and 12. RESULTS: When all subjects' data were pooled, the mean reduction in body weight (3.7+/-3.6 kg) was significant (P<0.0001) and as predicted, which suggested no compensation for the increase in EE. However, further examination revealed a large individual variability in weight change ( 14.7 to +1.7 kg). Subjects were identified as compensators (C) or noncompensators (NC) based on their actual weight loss (mean NC=6.3+/-3.2 kg and C=1.5+/- 2.5 kg) relative to their predicted weight loss. C and NC were characterized by their different metabolic and behavioural compensatory responses. Moderate changes in RMR occurred in C (-69.2+/-268.7 kcal day(-1)) and NC (14.2+/-242.7 kcal day( 1)). EI and average daily subjective hunger increased by 268.2+/-455.4 kcal day( 1) and 6.9+/-11.4 mm day(-1) in C, whereas EI decreased by 130+/-485 kcal day(-1) and there was no change in subjective appetite (0.4+/-9.6 mm day(-1)) in NC. CONCLUSION: These results demonstrate that expressing the exercise-induced change in body weight as a group mean conceals the large inter-individual variability in body weight and compensatory responses. Individuals who experience a lower than predicted weight loss are compensating for the increase in EE. PMID- 17848942 TI - Optimum duration of breast cancer follow-up: a continuing controversy. PMID- 17848944 TI - Reduced DNA repair in BRCA1 mutation carriers undetectable before onset of breast cancer? PMID- 17848946 TI - Enhanced repair of DNA interstrand crosslinking in ovarian cancer cells from patients following treatment with platinum-based chemotherapy. AB - Despite high tumour response rates to platinum-based chemotherapy in ovarian cancer survival is poor due to the emergence of drug resistance. Mechanistic studies in clinical material have been hampered by the unavailability of sensitive methods to detect the critical drug-induced effects in individual cells. A modification of the single cell gel electrophoresis (comet) assay allows the sensitive detection of DNA interstrand crosslinking in both tumour and normal cells derived directly from clinical material. Tumour cells isolated from 50 ovarian cancer patients were treated ex vivo with 100 microM cisplatin for 1 h and crosslink formation and repair (unhooking) measured. No significant difference in the peak level of crosslinking in tumour cells was observed between patients who were either newly diagnosed or previously treated with platinum based therapy, or between tumour and mesothelial cells from an individual patient. This indicates no difference in cellular mechanisms such as drug transport or detoxification. In contrast, the percentage repair (unhooking) of DNA interstrand crosslinks was much greater in the group of treated patients. At 24 h in the 36 newly diagnosed patient tumour samples, only one gave >50% repair and 23 gave <10% repair; however, 19 out of 22 treated patient samples gave >10% repair and 14 showed >50% repair. The estimated median difference (newly diagnosed minus treated) was -52 (95% CI -67 to -28), and the P-value from a Mann Whitney test was <0.001. In eight patients, it was possible to obtain tumour samples prior to any chemotherapy, and also on relapse or at interval debulking surgery following platinum-based chemotherapy. In these patients, the mean % repair prior to therapy was 2.85 rising to 71.23 following treatment. These data demonstrate increased repair of DNA interstrand crosslinks in ovarian tumour cells following platinum therapy which may contribute to clinical acquired resistance. PMID- 17848947 TI - [18F]2-fluoro-2-deoxy-D-glucose incorporation by AGS gastric adenocarcinoma cells in vitro during response to epirubicin, cisplatin and 5-fluorouracil. AB - Decreased tumour [(18)F]2-fluoro-2-deoxy-D-glucose ((18)FDG) incorporation is related to response however its significance at the cell level in gastro oesophageal cancer and how it relates to cell death is unknown. Here human gastric adenocarcinoma (AGS) cells were treated with lethal dose 10 and 50 (LD(10) and LD(50)), determined by using the MTT assay, of the three drugs, epirubicin, 5-fluorouracil and cisplatin, commonly used in the treatment of patients with gastro-oesophageal cancer. (18)FDG incorporation was determined after 48 and 72 h of treatment with each drug and related to drug-induced changes in glucose transport, hexokinase activity, cell cycle distribution and annexin V PE binding (a measure of apoptosis). Treatment of cells for 48 and 72 h with LD(50) doses of cisplatin resulted in reductions in (18)FDG incorporation of 27 and 25% respectively and of 5-fluorouracil reduced (18)FDG incorporation by 34 and 33% respectively: epirubicin treatment reduced incorporation by 30 and 69% respectively. Cells that had been treated for 72 h with each drug were incubated in drug-free media for a further 6 days to determine their ability to recover. Comparison of the ability to recover from the chemotherapy agent, with (18)FDG incorporation before the recovery period allowed an assessment of the predictive ability of (18)FDG incorporation. Cells treated with either 5-fluorouracil or cisplatin demonstrated recovery on removal of the drug. In contrast, cells treated with epirubicin did not recover corresponding with the greatest 72 h treatment decrease in (18)FDG incorporation. In contrast to adherent cells treated with cisplatin or 5-fluorouracil, adherent epirubicin-treated cells also exhibited very high levels of apoptosis. Glucose transport was decreased after each treatment whilst hexokinase activity was only decreased after 72 h of treatment with each drug. There was no consistent relationship observed between (18)FDG incorporation and cell cycle distribution. Our results show that at the tumour cell level in gastric tumour cells, decreased (18)FDG incorporation and glucose transport, accompanies therapeutic growth inhibition. (18)FDG incorporation is particularly diminished in cells exhibiting apoptosis. PMID- 17848948 TI - In vitro and in vivo reversal of resistance to 5-fluorouracil in colorectal cancer cells with a novel stealth double-liposomal formulation. AB - Drug resistance is a major cause of treatment failure in cancer chemotherapy, including that with the extensively prescribed antimetabolite, 5-fluorouracil (5 FU). In this study, we tried to reverse 5-FU resistance by using a double-punch strategy: combining 5-FU with a biochemical modulator to improve its tumoural activation and encapsulating both these agents in one same stealth liposome. Experiments carried out in the highly resistant, canonical SW620 human colorectal model showed a up to 80% sensitisation to 5-FU when these cells were treated with our liposomal formulation. Results with this formulation demonstrated 30% higher tumoural drug uptake, better activation with increased active metabolites including critical-5-fluoro-2-deoxyuridine-5-monophosphate, superior inhibition (98%) of tumour thymidylate synthase, and subsequently, higher induction of both early and late apoptosis. Drug monitoring showed that higher and sustained exposure was achieved in rats treated with liposomal formulation. When examined in a xenograft animal model, our dual-agent liposomal formulation caused a 74% reduction in tumour size with a mean doubling in survival time, whereas standard 5-FU failed to exhibit significant antiproliferative activity as well as to increase the lifespan of tumour-bearing mice. Taken collectively, our data suggest that resistance to 5-FU can be overcome through a better control of its intratumoural activation and the use of an encapsulated formulation. PMID- 17848949 TI - Sequence dependent antitumour efficacy of the vascular disrupting agent ZD6126 in combination with paclitaxel. AB - The clinical success of small-molecule vascular disrupting agents (VDAs) depends on their combination with conventional therapies. Scheduling and sequencing remain key issues in the design of VDA-chemotherapy combination treatments. This study examined the antitumour activity of ZD6126, a microtubule destabilising VDA, in combination with paclitaxel (PTX), a microtubule-stabilising cytotoxic drug, and the influence of schedule and sequence on the efficacy of the combination. Nude mice bearing MDA-MB-435 xenografts received weekly cycles of ZD6126 (200 mg kg(-1) i.p.) administered at different times before or after PTX (10, 20, and 40 mg kg(-1) i.v.). ZD6126 given 2 or 24 h after PTX showed no significant benefit, a result that was attributed to a protective effect of PTX against ZD6126-induced vascular damage and tumour necrosis, a hallmark of VDA activity. Paclitaxel counteracting activity was reduced by distancing drug administrations, and ZD6126 given 72 h after PTX potentiated the VDA's antitumour activity. Schedules with ZD6126 given before PTX improved therapeutic activity, which was paralleled by a VDA-induced increase in cell proliferation in the viable tumour tissue. Paclitaxel given 72 h after ZD6126 yielded the best response (50% tumours regressing). A single treatment with ZD6126 followed by weekly administration of PTX was sufficient to achieve a similar response (57% remissions). These findings show that schedule, sequence and timing are crucial in determining the antitumour efficacy of PTX in combination with ZD6126. Induction of tumour necrosis and increased proliferation in the remaining viable tumour tissue could be exploited as readouts to optimise schedules and maximise therapeutic efficacy. PMID- 17848950 TI - Frequent epigenetic inactivation of secreted frizzled-related protein 2 (SFRP2) by promoter methylation in human gastric cancer. AB - The role of secreted frizzled-related protein (SFRP) genes in gastric cancer remains largely unknown. We determined the frequency and functional significance of SFRPs hypermethylation in human gastric cancer. The expression and methylation status of four SFRP members (SFRP1, 2, 4, and 5) in primary gastric cancer samples was screened. The biological effects of SFRP were analysed by flow cytometry, cell viability assay and in vivo tumour growth in nude mice. Among the four SFRPs, only SFRP2 was significantly downregulated in gastric cancer as compared to adjacent non-cancer samples (P<0.01). Promoter hypermethylation of SFRP2 was detected in 73.3% primary gastric cancer tissues, 37.5% of samples showing intestinal metaplasia and 20% adjacent normal gastric tissues. Bisulphite DNA sequencing confirmed the densely methylated SFRP2 promoter region. Demethylation treatment restored the expression of SFRP2 in gastric cancer cell lines. Forced expression of SFRP2 induced cell apoptosis, inhibited proliferation of gastric cancer cells and suppressed tumour growth in vivo. Moreover, methylated SFRP2 was detected in 66.7% of serum samples from cancer patients but not in normal controls. In conclusion, epigenetic inactivation of SFRP2 is a common and early event contributing to gastric carcinogenesis and may be a potential biomarker for gastric cancer. PMID- 17848951 TI - Distinct molecular phenotype of inflammatory breast cancer compared to non inflammatory breast cancer using Affymetrix-based genome-wide gene-expression analysis. AB - The present study aims at a platform-independent confirmation of previously obtained cDNA microarray results on inflammatory breast cancer (IBC) using Affymetrix chips. Gene-expression data of 19 IBC and 40 non-IBC specimens were subjected to clustering and principal component analysis. The performance of a previously identified IBC signature was tested using clustering and gene set enrichment analysis. The presence of different cell-of-origin subtypes in IBC was investigated and confirmed using immunohistochemistry on a TMA. Differential gene expression was analysed using SAM and topGO was used to identify the fingerprints of a pro-metastatic-signalling pathway. IBC and non-IBC have distinct gene expression profiles. The differences in gene expression between IBC and non-IBC are captured within an IBC signature, identified in a platform-independent manner. Part of the gene-expression differences between IBC and non-IBC are attributable to the differential presence of the cell-of-origin subtypes, since IBC primarily segregated into the basal-like or ErbB2-overexpressing group. Strikingly, IBC tumour samples more closely resemble the gene-expression profile of T1/T2 tumours than the gene-expression profile or T3/T4 tumours. We identified the insulin-like growth factor-signalling pathway, potentially contributing to the biology of IBC. Our previous results have been validated in a platform independent manner. The distinct biological behaviour of IBC is reflected in a distinct gene-expression profile. The fact that IBC tumours are quickly arising tumours might explain the close resemblance of the IBC gene-expression profile to the expression profile of T1/T2 tumours. PMID- 17848952 TI - Marrow angiogenesis-associated factors as prognostic biomarkers in patients with acute myelogenous leukaemia. AB - Bone marrow (BM) neoangiogenesis plays an important role in acute myelogenous leukaemia (AML), and depends on the interplay of members of the vascular endothelial growth factor (VEGF) and angiopoietin (Ang) families. We determined the marrow levels of seven molecules associated with angiogenesis in 52 AML patients before chemotherapy and 20 healthy controls: VEGF-A, VEGF/PlGF, VEGF-C, VEGF-D, Ang-1, Ang-2, and Tie-2. All the molecules were quantified using enzyme linked immunosorbent assay (ELISA). Comparing to normal controls, the marrow levels of VEGF/PlGF, Ang-2, and Tie-2 were significantly higher, and those of VEGF-C and Ang-1 were significantly lower in the AML patients (P<0.001). A total of 31 patients were further subjected to survival analysis. Patients with lower Tie-2 (<26 ng ml(-1)) and Ang-2 levels (<4500 pg ml(-1)) displayed a survival advantage (P=0.037 and 0.042, respectively), same as patients with higher VEGF/PlGF (> or =1 pg ml(-1)) and VEGF-D levels (> or =350 pg ml(-1)) (P=0.020 and 0.016, respectively). An angio-index ((Ang-2 x Tie-2)/(VEGF/PlGF x VEGF-D)) was established and multivariate Cox regression analysis revealed that patients with higher angio-index values (> or =50) displayed poor prognosis (hazard ratio 5.91, 95% confidence interval 1.99-17.56; P=0.001). The angio-index is closely associated with the clinical outcome of AML patients and may be valuable in disease prognosis. PMID- 17848953 TI - Colocalisation of CD9 and mortalin in CD9-induced mitotic catastrophe in human prostate cancer cells. AB - CD9, a member of the tetraspanin family of proteins, is involved in a variety of cellular interactions with many other proteins and molecules. Although CD9 has been implicated in cell fusion, migration and cancer progression, the detailed function of this protein is not completely understood and likely depends on interactions with different protein partners, which are not yet all known. Using co-immunoprecipitation and mass-spectrometric protein sequencing, we have identified in prostate cancer cells, a novel CD9 partner, the 75-kDa protein HSPA9B, also known as mortalin. We further show that introduction and overexpression of wild-type CD9 into human PC-3 prostate cancer cells induces mitotic catastrophe. We also demonstrate, by immunocolocalisation studies, the interaction of CD9 and mortalin in PC-3 cells undergoing mitotic catastrophe. Our results not only identified mortalin as a new CD9 partner, but also clarify the mechanisms by which CD9 may control prostate cancer progression. PMID- 17848954 TI - Overexpression of matrix metalloproteinases and their inhibitors in mononuclear inflammatory cells in breast cancer correlates with metastasis-relapse. AB - An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinase (MMP)-1, -2, -7, -9, -11, -13 and 14, tissular inhibitors of metalloproteinase (TIMP)-1, -2 and -3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast were performed. To identify specific groups of tumours with distinct expression profiles the data were analysed by unsupervised hierarchical cluster analysis by each cellular type. We did not find well-defined cluster of cases for tumour cells or fibroblastic cells. However, for mononuclear inflammatory cells the dendogram shows a first-order division of the tumours into two distinct MMP/TIMP molecular profiles, designated group 1 (n=89) and group 2 (n=42). Matrix metalloproteinase-7, -9, -11, -13 and -14, and TIMP-1 and -2, were identified as showing significant high expression in group 2 compared with group 1. Multivariate analysis demonstrated that clustering for mononuclear inflammatory cells was the most potent independent factor associated with distant relapse-free survival (group 2: 5.6 (3.5-9.6), P<0.001). We identify a phenotype of mononuclear inflammatory cells infiltrating tumours, which is associated with the development of distant metastasis. Therefore, this finding suggests that these host inflammatory cells could be a possible target for inhibition of metastasis. PMID- 17848955 TI - Decreased number of mast cells infiltrating into needle biopsy specimens leads to a better prognosis of prostate cancer. AB - Mast cell infiltration is often observed around human tumours. Inflammatory cells such as macrophages, neutrophils and mast cells infiltrating around tumours are known to contribute to tumour growth; however, the clinical significance of mast cell invasion in prostate cancer (PCa) has not been investigated. Mast cell infiltration was evaluated in 104 patients (age range, 45-88 years; median, 72 years), who underwent needle biopsy of the prostate and were confirmed to have PCa. Needle biopsy specimens of prostate were sliced into 5-microm-thick sections and immunostained for mast cells with monoclonal antibody against mast cell specific tryptase. Mast cells were counted systematically under a microscope (x 400 magnification), and the relations between mast cell numbers and clinicopathologic findings were evaluated. The mast cell count was evaluated for prognostic value by multivariate analysis. Mast cells were immunostained around the cancer foci. The median number of mast cells in each case was 16. The mast cell count was higher around cancer foci in patients with higher Gleason scores than in those with low Gleason scores. The mast cell number correlated well with clinical stage (P<0.001). Prostate-specific antigen-free survival of patients with higher mast cell counts was better than that in patients with lower mast cell counts (P<0.001). Multivariate analysis revealed that mast cell count was a significant prognostic factor (P<0.005). The number of mast cells infiltrating around cancer foci in prostate biopsy specimens can be a significant prognostic factor of PCa. PMID- 17848956 TI - TGFBR1(*)6A and Int7G24A variants of transforming growth factor-beta receptor 1 in Swedish familial and sporadic breast cancer. AB - Two common variants in transforming growth factor-beta receptor 1 (TGFBR1), TGFBR1(*)6A and Int7G24A, A allele, have been shown to act as low-penetrance tumour susceptibility alleles in several common cancers, including breast cancer. We evaluated the TGFBR1 9A/6A and Int7G24A variant frequencies in two breast cancer cohorts; a population-based cohort of breast cancer with defined family history (n=459) and in breast cancer patients from a familial cancer clinic (n=340) and in 856 controls from the Stockholm region. The familial patients from both cohorts were further divided into high- and low-risk familial breast cancer based on pedigree analysis. There was no overall association with either variant and breast cancer risk. The TGFBR1(*)6A allelic frequency was, however, higher in low-risk familial breast cancer (0.138), compared to controls (0.106; P=0.04). No significant difference was found in the high-risk familial (0.102) or sporadic cases (0.109; P=0.83 and 0.83, respectively). TGFBR1(*)6A carrier status was further associated with a high-grade sporadic breast cancer (odds ratio: 2.27; 95% confidence interval: 1.01-5.11; P=0.049). These results indicate that the TGFBR1(*)6A variant may be associated with an increased risk of low-risk familial breast cancer and might be a marker for poorly differentiated breast cancer. The Int7G24A variant was not associated with breast cancer risk or clinical presentation of the disease including prognosis in our material. PMID- 17848957 TI - Detection of distant metastases in patients with oesophageal or gastric cardia cancer: a diagnostic decision analysis. AB - Computed tomography (CT) is presently a standard procedure for the detection of distant metastases in patients with oesophageal or gastric cardia cancer. We aimed to determine the additional diagnostic value of alternative staging investigations. We included 569 oesophageal or gastric cardia cancer patients who had undergone CT neck/thorax/abdomen, ultrasound (US) abdomen, US neck, endoscopic ultrasonography (EUS), and/or chest X-ray for staging. Sensitivity and specificity were first determined at an organ level (results of investigations, i.e., CT, US abdomen, US neck, EUS, and chest X-ray, per organ), and then at a patient level (results for combinations of investigations), considering that the detection of distant metastases is a contraindication to surgery. For this, we compared three strategies for each organ: CT alone, CT plus another investigation if CT was negative for metastases (one-positive scenario), and CT plus another investigation if CT was positive, but requiring that both were positive for a final positive result (two-positive scenario). In addition, costs, life expectancy and quality adjusted life years (QALYs) were compared between different diagnostic strategies. CT showed sensitivities for detecting metastases in celiac lymph nodes, liver and lung of 69, 73, and 90%, respectively, which was higher than the sensitivities of US abdomen (44% for celiac lymph nodes and 65% for liver metastases), EUS (38% for celiac lymph nodes), and chest X-ray (68% for lung metastases). In contrast, US neck showed a higher sensitivity for the detection of malignant supraclavicular lymph nodes than CT (85 vs 28%). At a patient level, sensitivity for detecting distant metastases was 66% and specificity was 95% if only CT was performed. A higher sensitivity (86%) was achieved when US neck was added to CT (one-positive scenario), at the same specificity (95%). This strategy resulted in lower costs compared to CT only, at an almost similar (quality adjusted) life expectancy. Slightly higher specificities (97-99%) were achieved if liver and/or lung metastases found on CT, were confirmed by US abdomen or chest X-ray, respectively (two-positive scenario). These strategies had only slightly higher QALYs, but substantially higher costs. The combination of CT neck/thorax/abdomen and US neck was most cost effective for the detection of metastases in patients with oesophageal or gastric cardia cancer, whereas the performance of CT only had a lower sensitivity for metastases detection and higher costs. The role of EUS seems limited, which may be due to the low number of M1b celiac lymph nodes detected in this series. It remains to be determined whether the application of positron emission tomography will further increase sensitivities and specificities of metastases detection without jeopardising costs and QALYs. PMID- 17848958 TI - Phase I study of S-1, docetaxel and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer. AB - The aim of this dose escalation study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs) and preliminary efficacy of docetaxel, S-1 and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer. Seventeen patients received oral S-1 (40 mg m(-2) bid) on days 1 14, intravenous cisplatin (60 mg m(-2)) and docetaxel (60, 70 or 80 mg m(-2) depending on DLT) on day 8 every 3 weeks. The MTD of this combination was presumed to be docetaxel 70 mg m(-2). At this dose level, 40% of the patients (two of five) developed grade 4 neutropenia and 20% (one of five) exhibited grade 3 nausea during the first course. Therefore, the recommended dose of docetaxel was defined as 60 mg m(-2). The DLT was neutropenia. The response rate (RR) was 88.2% (15 of 17), consisting of one complete response and 14 partial responses. There were two stable diseases but no progressive disease. Of these 15 responders, four (23.5%) with high VEGF expression showed rapid tumour regression and achieved downstaging, leading to subsequent curative gastrectomy. Three of these have been disease free for about 3 years, suggesting a complete cure. In conclusion, this regimen was tolerable and showed a quite high RR, with an appreciable downstaging rate in metastatic gastric cancer. PMID- 17848959 TI - First-into-man phase I and pharmacokinetic study of XR5944.14, a novel agent with a unique mechanism of action. AB - The bis-phenazine XR5944.14 is a novel cytotoxic agent which intercalates into DNA and inhibits transcription. The objectives of this study were to determine the dose-limiting toxicity (DLT), the maximum tolerated dose (MTD) and to describe the pharmacokinetics (PKs) of XR5944.14 when given at doses ranging from 3.6 to 36 mg m(-2) every 3 weeks to patients with advanced tumours. Twenty-seven patients were treated with a total of 77 cycles. Dose-limiting toxicities occurred at doses > or =24 mg m(-2). Oral mucositis was the most common DLT. Two patients developed acute renal failure possibly related to the study drug. Other less-severe toxicities were diarrhoea, nausea, vomiting and fatigue. Haematological toxicity was mild. One patient showed an objective partial response. Pharmacokinetic analysis was performed during the first cycle of treatment and plasma was assayed for XR5944.14 using a validated liquid chromatography tandem mass spectrometry. The systemic exposure of XR5944.14 increased more than proportionally with increasing dose, with inter-patient variability increasing from dose level 24 mg m(-2) onwards. The lack of correlation between toxicity and PK values makes it difficult to recommend a dose for further study in phase 2 trials. More work is needed to explain the inter- and intra-individual variation in PKs and pharmacodynamics. PMID- 17848960 TI - Correction of murine hemophilia A and immunological differences of factor VIII variants delivered by helper-dependent adenoviral vectors. AB - Bioengineering of the factor VIII (FVIII) molecule has led to the production of variants that overcome poor secretion and/or rapid inactivation. We tested six modified FVIII variants for in vivo efficacy by expressing them from helper dependent adenoviral (HD-Ad) vectors. We constructed a wild-type (WT) variant, a B-domain-deleted (BDD) variant, a point mutant for improved secretion (F309S), a variant with a partial B-domain deletion for improved secretion (N6), a combination of the point mutant and partial BDD variant (F309N6), and an inactivation-resistant (IR8) FVIII variant. All the constructs expressed functional protein after injection of high-dose HD-Ad. Activity ranged from 20 to 50% with WT, to approximately 100% with the N6 and F309N6 variants. Interestingly, mice treated with N6 showed long-term FVIII activity and phenotypic correction for up to 74 weeks, with low anti-FVIII antibody titer. Importantly, the N6 variant was therapeutically efficacious even after a 50% reduction of viral dose, thereby indicating that transgene modification itself can improve the dose efficacy of HD-Ad. This finding is significant, because dose efficacy is a key factor in clinical application. In summary, bioengineering of the FVIII molecule may be an effective approach to improving the safety, immunogenicity, and efficacy of HD-Ad gene therapy in hemophilia A (HA). PMID- 17848961 TI - Fully detargeted polyethylene glycol-coated adenovirus vectors are potent genetic vaccines and escape from pre-existing anti-adenovirus antibodies. AB - Genetic vaccination with adenoviral (Ad) gene transfer vectors requires transduction of professional antigen-presenting cells. However, because the natural Ad receptors are expressed on many cell types, the Ad vectors currently in use are characterized by high promiscuity. In fact, the majority of injected Ad vector particles are likely to transduce non-target cells. We have analyzed various sizes of polyethylene glycol (PEG) molecules for vector particle detargeting, and our data provide evidence that the size of the PEG determines detargeting efficiency. With the use of appropriately large PEG molecules, vector particles were detargeted from muscle after local delivery and from liver after systemic delivery in mouse models. Surprisingly, fully detargeted PEGylated Ad vectors still induced strong cellular and humoral immune responses to vector encoded transgene products. Also, injection of PEGylated and non-PEGylated vector particles resulted in similar kinetics of transgene product-specific cytotoxic immune responses, thereby suggesting that the same cell types were involved in their induction. Furthermore, we showed that PEGylated vectors evade neutralizing anti-Ad antibodies in vivo. This feature might help circumvent the recognized limitation imposed by the widespread occurrence of anti-Ad immunity in the human population. We suggest that PEGylated Ad particles with significantly reduced promiscuity may qualify as a novel and safe vector format for genetic vaccination. PMID- 17848962 TI - Oncolytic adenoviruses kill breast cancer initiating CD44+CD24-/low cells. AB - Cancer stem cells have been indicated in the initiation of tumors and are even found to be responsible for relapses after apparently curative therapies have been undertaken. In breast cancer, they may reside in the CD44(+)CD24(-/low) population. The use of oncolytic adenoviruses presents an attractive anti-tumor approach for eradication of these cells because their entry occurs through infection and they are, therefore, not susceptible to those mechanisms that commonly render stem cells resistant to many drugs. We isolated CD44(+)CD24( /low) cells from patient pleural effusions and confirmed stem cell-like features including oct4 and sox2 expression and Hoechst 33342 exclusion. CD44(+)CD24( /low) cells, including the Hoechst excluding subpopulation, could be effectively killed by oncolytic adenoviruses Ad5/3-Delta24 and Ad5.pk7-Delta24. In mice, CD44(+)CD24(-/low) cells formed orthotopic breast tumors but virus infection prevented tumor formation. Ad5/3-Delta24 and Ad5.pk7-Delta24 were effective against advanced orthotopic CD44(+)CD24(-/low)-derived tumors. In summary, Ad5/3 Delta24 and Ad5.pk7-Delta24 can kill CD44(+)CD24(-/low), and also committed breast cancer cells, making them promising agents for treatment of breast cancer. PMID- 17848964 TI - Therapeutic use of rTMS. PMID- 17848965 TI - Dendritic mRNA: transport, translation and function. AB - Many cellular functions require the synthesis of a specific protein or functional cohort of proteins at a specific time and place in the cell. Local protein synthesis in neuronal dendrites is essential for understanding how neural activity patterns are transduced into persistent changes in synaptic connectivity during cortical development, memory storage and other long-term adaptive brain responses. Regional and temporal changes in protein levels are commonly coordinated by an asymmetric distribution of mRNAs. This Review attempts to integrate current knowledge of dendritic mRNA transport, storage and translation, placing particular emphasis on the coordination of regulation and function during activity-dependent synaptic plasticity in the adult mammalian brain. PMID- 17848967 TI - ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. AB - Reactive oxygen species (ROS) have been shown to be toxic but also function as signalling molecules. This biological paradox underlies mechanisms that are important for the integrity and fitness of living organisms and their ageing. The pathways that regulate ROS homeostasis are crucial for mitigating the toxicity of ROS and provide strong evidence about specificity in ROS signalling. By taking advantage of the chemistry of ROS, highly specific mechanisms have evolved that form the basis of oxidant scavenging and ROS signalling systems. PMID- 17848966 TI - Chromosomal passengers: conducting cell division. AB - Mitosis and meiosis are remarkable processes during which cells undergo profound changes in their structure and physiology. These events are orchestrated with a precision that is worthy of a classical symphony, with different activities being switched on and off at precise times and locations throughout the cell. One essential 'conductor' of this symphony is the chromosomal passenger complex (CPC), which comprises Aurora-B protein kinase, the inner centromere protein INCENP, survivin and borealin (also known as Dasra-B). Studies of the CPC are providing insights into its functions, which range from chromosome-microtubule interactions to sister chromatid cohesion to cytokinesis, and constitute one of the most dynamic areas of ongoing mitosis and meiosis research. PMID- 17848968 TI - A ciliary timer for S-phase entry. PMID- 17848970 TI - Adaptive peaks in a flat-fish: adaptive divergence overcoming gene flow. PMID- 17848971 TI - Floral evolution: spurred on by pollinators. PMID- 17848972 TI - Factors affecting the dynamics of the honeybee (Apis mellifera) hybrid zone of South Africa. AB - Hybrid zones are found wherever two populations distinguishable on the basis of heritable characters overlap spatially and temporally and hybridization occurs. If hybrids have lower fitness than the parental types a tension zone may emerge, in which there is a barrier to gene flow between the two parental populations. Here we discuss a hybrid zone between two honeybee subspecies, Apis mellifera capensis and A. m. scutellata and argue that this zone is an example of a tension zone. This tension zone is particularly interesting because A. m. capensis can be a lethal social parasite of A. m. scutellata. However, despite its parasitic potential, A. m. capensis appears to be unable to increase its natural range unassisted. We propose three interlinked mechanisms that could maintain the South African honeybee hybrid zone: (1) low fitness of intercrossed and genetically mixed colonies arising from inadequate regulation of worker reproduction; (2) higher reproductive success of A. m. scutellata via both high dispersal rates into the hybrid zone and increased competitiveness of males, countered by (3) the parasitic nature of A. m. capensis. PMID- 17848973 TI - Adaptive divergence in a high gene flow environment: Hsc70 variation in the European flounder (Platichthys flesus L.). AB - Little is known about local adaptations in marine fishes since population genetic surveys in these species have typically not applied genetic markers subject to selection. In this study, we used a candidate gene approach to investigate adaptive population divergence in the European flounder (Platichthys flesus L.) throughout the northeastern Atlantic. We contrasted patterns of genetic variation in a presumably neutral microsatellite baseline to patterns from a heat-shock cognate protein gene, Hsc70. Using two different neutrality tests we found that the microsatellite data set most likely represented a neutral baseline. In contrast, Hsc70 strongly deviated from neutral expectations. Importantly, when estimating standardized levels of population divergence (F(ST)'), we also found a large discrepancy in the patterns of structuring in the two data sets. Thus, samples grouped according to geographical or historical proximity with regards to microsatellites, but according to environmental similarities with regards to Hsc70. The differences between the data sets were particularly pronounced in pairwise comparisons involving populations in the western and central Baltic Sea. For instance, the genetic differentiation between geographically close Baltic Sea and North Sea populations was found to be 0.02 and 0.45 for microsatellites and Hsc70 respectively. Our results strongly suggest adaptive population divergence and indicate local adaptations at the DNA level in a background of high levels of gene flow, typically found in many marine fish species. Furthermore, this study highlights the usefulness of the candidate gene approach for demonstrating local selection in non-model organisms such as most marine fishes. PMID- 17848974 TI - The quest for natural selection in the age of comparative genomics. AB - Continued genome sequencing has fueled progress in statistical methods for understanding the action of natural selection at the molecular level. This article reviews various statistical techniques (and their applicability) for detecting adaptation events and the functional divergence of proteins. As large scale automated studies become more frequent, they provide a useful resource for generating biological null hypotheses for further experimental and statistical testing. Furthermore, they shed light on typical patterns of lineage-specific evolution of organisms, on the functional and structural evolution of protein families and on the interplay between the two. More complex models are being developed to better reflect the underlying biological and chemical processes and to complement simpler statistical models. Linking molecular processes to their statistical signatures in genomes can be demanding, and the proper application of statistical models is discussed. PMID- 17848975 TI - Spatial genetic structure in the Laperrine's olive (Olea europaea subsp. laperrinei), a long-living tree from the central Saharan mountains. AB - The Laperrine's olive (Olea europaea subsp. laperrinei) is an emblematic species of the Sahelo-Saharan Mountains. Populations of this tree are locally threatened by extinction due to climatic vicissitudes and human activities, particularly in Niger and Algeria. In order to study the spatial genetic structure and the dynamics of O. e. laperrinei populations, we sampled trees in four isolated mountain ranges (Tassili n'Ajjer and Hoggar (Algeria), Tamgak and Bagzane (Niger)). A total of 237 genets were identified using nuclear microsatellites. Phylogenetic reconstruction based on plastid DNA data supported a maternal origin of O. e. laperrinei populations in South Algeria, where a higher allelic richness was observed. Based on nuclear microsatellite data, two levels of structure were revealed: first, individuals from Niger and Algeria were separated in two distinct groups; second, four less differentiated clusters corresponded to the four studied mountain ranges. These results give support to the fact that desert barriers have greatly limited long distance gene flow. Within populations, pairwise kinship coefficients were significantly correlated to geographical distance for Niger populations but not for Algerian mountains. Historical factors and habitat heterogeneity may explain the differences observed. We conclude that the Hoggar acts as an important genetic reservoir that has to be taken into account in future conservation programmes. Moreover, very isolated endangered populations (for example, Bagzane) displaying evident genetic particularities have to be urgently considered for their endemism. PMID- 17848976 TI - Validation of bioelectrical impedance analysis (BIA) for estimation of body composition in Black, White and Hispanic adolescent girls. AB - AIM: Equations for estimating % fat mass (%BF) and fat-free mass (FFM) from bioelectrical impedance analysis (BIA) that work in adolescent girls from different racial/ethnic backgrounds are not available. We investigated whether race/ethnicity influences estimation of body composition in adolescent girls. PRINCIPAL PROCEDURES: Prediction equations were developed for estimating FFM and %BF from BIA in 166 girls, 10-15 years old, consisting of 51 Black (B), 45 non Black Hispanic (H), 55 non-Hispanic White (W) and 15 mixed (M) race/ethnicity girls, using dual energy x-ray absorptiometry (DXA) as the criterion method. FINDINGS: Black girls had similar %BF compared to other groups, yet were heavier per unit of height according to body mass index (BMI: kg.m(-2)) due to significantly greater FFM. BIA resistance index, age, weight and race/ethnicity were all significant predictors of FFM (R(2) = 0.92, SEE = 1.81 kg). Standardized regression coefficients showed resistance index (0.63) and weight (0.34) were the most important predictors of FFM. Errors in %BF (~2%) and FFM (~1.0 kg) were greater when race/ethnicity was not included in the equation, particularly in Black girls. We conclude the BIA-composition relationship in adolescent girls is influenced by race, and consequently have developed new BIA equations for adolescent girls for predicting FFM and %BF. PMID- 17848977 TI - Identifying and Predicting Offending Trajectories among Poor Children. AB - Using data from the Seattle Social Development Project, we identify childhood predictors of offending trajectories among poor children. Five trajectories are identified: nonoffenders, late onsetters, desisters, escalators, and chronic offenders. Among initial nonoffenders, late onsetters are distinguished from nonoffenders by early alcohol drinking. Among youths already delinquent at age 13, escalators are distinguished from desisters by poor family management, family conflict, association with antisocial peers, the presence of troubled children in their neighborhoods, and drug availability. In contrast to prior findings for a general urban sample, family factors significantly predict desistance from offending by age 18 in children from low-income families. PMID- 17848978 TI - Modeling the Etiology of Adolescent Substance Use: A Test of the Social Development Model. AB - The social development model is a general theory of human behavior that seeks to explain antisocial behaviors through specification of predictive developmental relationships. It incorporates the effects of empirical predictors ("risk factors" and "protective factors") for antisocial behavior and attempts to synthesize the most strongly supported propositions of control theory, social learning theory, and differential association theory. This article examines the power of social development model constructs measured at ages 9 to 10 and 13 to 14 to predict drug use at ages 17 to 18. The sample of 590 is from the longitudinal panel of the Seattle Social Development Project, which in 1985 sampled fifth grade students from high crime neighborhoods in Seattle, Washington. Structural equation modeling techniques were used to examine the fit of the model to the data. Although all but one path coefficient were significant and in the expected direction, the model did not fit the data as well as expected (CFI=.87). We next specified second-order factors for each path to capture the substantial common variance in the constructs' opportunities, involvement, and rewards. This model fit the data well (CFI=.90). We conclude that the social development model provides an acceptable fit to predict drug use at ages 17 to 18. Implications for the temporal nature of key constructs and for prevention are discussed. PMID- 17848979 TI - Association between vitamin D receptor gene haplotypes and chronic periodontitis among Japanese men. AB - BACKGROUND: The vitamin D receptor (VDR) is involved in a variety of biological processes, such as bone metabolism and modulation of the immune response. Recent findings suggest that the pathway involving bone mineral density-mediated effects is important for the development of periodontitis, but their effects of combined VDR gene polymorphisms have not been confirmed on periodontitis. We assessed the relationship between ApaI, BsmI, and FokI VDR polymorphisms and the risk of severe chronic periodontitis among Japanese adult men. MATERIALS AND METHODS: In a cross-sectional study, we examined 97 unrelated healthy Japanese men (mean age: 45.6 years, range: 22-59). A clinical examination was performed at a worksite health checkup, and information was obtained using a self-reported questionnaire. DNA was extracted from whole blood, and the VDR ApaI, BsmI, and FokI polymorphisms were genotyped using polymerase chain reaction. RESULTS: F-carriers of FokI VDR polymorphisms were less likely to develop severe chronic periodontitis than non-F-carriers (p = 0.09). The ApaI and BsmI VDR polymorphisms did not show significant differences in the alleles or genotypes between the subjects with or without severe chronic periodontitis. The haplotype analysis of the three combined VDR polymorphisms revealed that the Abf homozygote had a notably higher prevalence of severe chronic periodontitis than the others, and adjustments for age, smoking status, number of teeth present, and prevalence of diabetes did not change this association (OR = 7.5; 95% CI = 1.6-34.4; p = 0.01). CONCLUSION: The VDR haplotype constructed from the ApaI, BsmI, and FokI polymorphisms is related to the risk of severe chronic periodontitis in Japanese men. PMID- 17848980 TI - Chlamydia trachomatis infection of human trophoblast alters estrogen and progesterone biosynthesis: an insight into role of infection in pregnancy sequelae. AB - The trophoblast cells are in direct contact with endometrial tissues throughout gestation, playing important early roles in implantation and placentation. The physiologic significance and the operating mechanisms involved in probable altered trophoblast functions following Chlamydia trachomatis infection were investigated to determine if C. trachomatis initiates productive infection in trophoblast, effects of such event on the biosynthesis of cholesterol and its derivatives estrogen and progesterone; and the regulator of the biosynthesis of these hormones, human chorionic gonadotropin. Chlamydia trachomatis exhibited productive infection in trophoblast typified by inclusion formation observed when chlamydia elementary bodies were harvested from trophoblast and titrated onto HEp 2 cells. Assessment of the status of C. trachomatis in trophoblast showed a relative increase in protein of HSP-60 compared with MOMP, features suggestive of chlamydial chronicity. There was a decrease in cellular cholesterol of chlamydia infected trophoblast and a down regulation of HMG-CoA reductase. The levels of estrogen and progesterone were decreased, while the expression of aromatase and adrenodoxin reductase was up regulated. Also, there was a decrease in human chorionic gonadotropin expression. The implications of these findings are that C. trachomatis infection of trophoblast may compromise cellular cholesterol biosynthesis, thus depleting the substrate pool for estrogen and progesterone synthesis. This defect may impair trophoblast functions of implantation and placentation, and consequently affect pregnancy sequelae. PMID- 17848981 TI - An mRNA-protein fusion at N-terminus for evolutionary protein engineering. AB - A novel method to link a nascent protein (phenotype) to its mRNA (genotype) covalently through the N-terminus was developed. The mRNA harboring amber stop codon at just downstream of initiation site was hybridized with hydrazide modified ssDNA at upstream of coding region and was ligated to the DNA. This construct was then modified with 4-acetyl-phenylalanyl amber suppressor tRNA. This modified construct was fused with the nascent protein via the phenylalanine derivative when the mRNA uses the amber suppressor tRNA to decode the amber stop codon. The obtained fusion molecule was used successfully in selective enrichment experiments. It will be applicable for high-through-put screening in evolutionary protein engineering. In contrast to fusion molecules generated by other methods in which the protein is linked to genotype molecule through the C- terminus, our fusion molecule will serve to select a protein for which the C-terminus is essential to be active. PMID- 17848982 TI - High level glucose increases mutagenesis in human lymphoblastoid cells. AB - Epidemiological data have suggested an increased cancer rates in diabetic patients, for which the underlying mechanism is poorly understood. We studied whether high level of glucose (HG) treatment that mimic the hyperglycemic condition in diabetes mellitus is mutagenic. Mutagenesis studies were carried out at both hypoxanthine phosphoribosyltransferase (hprt) and thymidine kinase (tk) loci. Role of p53 in HG-induced mutagenesis was also investigated by using human lymphoblastoid cell lines derived from same donor but differs in p53 statuses; TK6 has wild-type p53, NH32 has null p53, and WTK1 has mutant p53 (ile237). In addition, we studied the influence of antioxidant treatment on HG-induced mutagenesis. Mutation fractions at both loci increased significantly in all three lines at 21 and 28 days after HG treatments. At tk locus, the increase of a class of mutants with normal growth rate is mainly responsible for the overall increased mutant fraction. Compared to TK6 cells, both NH32 and WTK1 cells showed an early onset of mutagenesis. Treatment of cells with antioxidant N-acetyl-L cysteine partially reduced HG induced mutagenesis. This study is the first to indicate that HG is able to induce gene mutation which may be one of the important mechanisms of diabetes-associated carcinogenesis. PMID- 17848983 TI - Versican expression during synovial joint morphogenesis. AB - The extracellular matrix (ECM) plays a critical role in governing cell behavior and phenotype during limb skeletogenesis. Chondroitin sulfate proteoglycans (Cspgs) are highly expressed in the ECM of precartilage mesenchymal condensations and are important to limb chondrogenesis and cartilage structure, but little is known regarding their involvement in formation of synovial joints in the embryonic limb. Matrix versican Cspg expression has previously been reported in the epiphysis of developing long bones and presumptive joint; however, detailed analysis has not yet been conducted. In the present study we immunolocalized versican and aggrecan Cspgs during chick elbow joint morphogenesis between HH st25-41 of development. In this study we show that versican and aggrecan expression initially overlapped in the incipient cartilage model of long bones in the wing, but versican was also highly expressed in the perichondrium and presumptive joint interzone during early stages of morphogenesis (HH st25-34). By HH st36-41 versican localization was restricted to the future articular surfaces of the developing joint and surrounding joint capsule while aggrecan localized in an immediately adjacent and predominately non-overlapping region of chondrogenic cells at the epiphyses. These results suggest a potential role for versican proteoglycan in development and maintenance of the synovial joint interzone. PMID- 17848984 TI - Reversal of systemic hypertension-associated cardiac remodeling in chronic pressure overload myocardium by ciglitazone. AB - Elevated oxidative stress has been characterized in numerous disorders including systemic hypertension, arterial stiffness, left ventricular hypertrophy (LVH) and heart failure. The peroxisome proliferator activated receptor gamma (PPARgamma) ameliorates oxidative stress and LVH. To test the hypothesis that PPARgamma decreased LVH and cardiac fibrosis in chronic pressure overload, in part, by increasing SOD, eNOS and elastin and decreasing NOX4, MMP and collagen synthesis and degradation, chronic pressure overload analogous to systemic hypertension was created in C57BL/6J mice by occluding the abdominal aorta above the kidneys (aortic stenosis-AS). The sham surgery was used as controls. Ciglitazone (CZ, a PPARgamma agonist, 4 microg/ml) was administered in drinking water. LV function was measured by M-Mode Echocardiography. We found that PPARgamma protein levels were increased by CZ. NOX-4 expression was increased by pressure-overload and such an increase was attenuated by CZ. SOD expression was not affected by CZ. Expression of iNOS was induced by pressure-overload, and such an increase was inhibited by CZ. Protein levels for MMP2, MMP-9, MMP-13 were induced and TIMP levels were decreased by pressure-overload. The CZ mitigated these levels. Collagen synthesis was increased and elastin levels were decreased by pressure overload and CZ ameliorated these changes. Histochemistry showed that CZ inhibited interstitial and perivascular fibrosis. Echocardiography showed that CZ attenuated the systolic and diastolic LV dysfunction induced by pressure overload. These observations suggested that CZ inhibited pressure-overlaod induced cardiac remodeling, and inhibition of an induction of NOX4, iNOS, MMP 2/MMP-13 expression and collagen synthesis/degradation may play a role in pressure-overload induced cardiac remodeling. PMID- 17848986 TI - The chop gene contains an element for the positive regulation of the mitochondrial unfolded protein response. AB - We have previously reported on the discovery of a mitochondrial specific unfolded protein response (mtUPR) in mammalian cells, in which the accumulation of unfolded protein within the mitochondrial matrix results in the transcriptional activation of nuclear genes encoding mitochondrial stress proteins such as chaperonin 60, chaperonin 10, mtDnaJ, and ClpP, but not those encoding stress proteins of the endoplasmic reticulum (ER) or the cytosol. Analysis of the chaperonin 60/10 bidirectional promoter showed that the CHOP element was required for the mtUPR and that the transcription of the chop gene is activated by mtUPR. In order to investigate the role of CHOP in the mtUPR, we carried out a deletion analysis of the chop promoter. This revealed that the transcriptional activation of the chop gene by mtUPR is through an AP-1 (activator protein-1) element. This site lies alongside an ERSE element through which chop transcription is activated in response to the ER stress response (erUPR). Thus CHOP can be induced separately in response to 2 different stress response pathways. We also discuss the potential signal pathway between mitochondria and the nucleus for the mtUPR. PMID- 17848985 TI - The p53 tumor suppressor-like protein nvp63 mediates selective germ cell death in the sea anemone Nematostella vectensis. AB - Here we report the identification and molecular function of the p53 tumor suppressor-like protein nvp63 in a non-bilaterian animal, the starlet sea anemone Nematostella vectensis. So far, p53-like proteins had been found in bilaterians only. The evolutionary origin of p53-like proteins is highly disputed and primordial p53-like proteins are variably thought to protect somatic cells from genotoxic stress. Here we show that ultraviolet (UV) irradiation at low levels selectively induces programmed cell death in early gametes but not somatic cells of adult N. vectensis polyps. We demonstrate with RNA interference that nvp63 mediates this cell death in vivo. Nvp63 is the most archaic member of three p53 like proteins found in N. vectensis and in congruence with all known p53-like proteins, nvp63 binds to the vertebrate p53 DNA recognition sequence and activates target gene transcription in vitro. A transactivation inhibitory domain at its C-terminus with high homology to the vertebrate p63 may regulate nvp63 on a molecular level. The genotoxic stress induced and nvp63 mediated apoptosis in N. vectensis gametes reveals an evolutionary ancient germ cell protective pathway which relies on p63-like proteins and is conserved from cnidarians to vertebrates. PMID- 17848987 TI - Liposome-mediated cellular delivery of active gp91(phox). AB - BACKGROUND: Gp91(phox) is a transmembrane protein and the catalytic core of the NADPH oxidase complex of neutrophils. Lack of this protein causes chronic granulomatous disease (CGD), a rare genetic disorder characterized by severe and recurrent infections due to the incapacity of phagocytes to kill microorganisms. METHODOLOGY: Here we optimize a prokaryotic cell-free expression system to produce integral mammalian membrane proteins. CONCLUSIONS: Using this system, we over-express truncated forms of the gp91(phox) protein under soluble form in the presence of detergents or lipids resulting in active proteins with a "native like" conformation. All the proteins exhibit diaphorase activity in the presence of cytosolic factors (p67(phox), p47(phox), p40(phox) and Rac) and arachidonic acid. We also produce proteoliposomes containing gp91(phox) protein and demonstrate that these proteins exhibit activities similar to their cellular counterpart. The proteoliposomes induce rapid cellular delivery and relocation of recombinant gp91(phox) proteins to the plasma membrane. Our data support the concept of cell-free expression technology for producing recombinant proteoliposomes and their use for functional and structural studies or protein therapy by complementing deficient cells in gp91(phox) protein. PMID- 17848988 TI - Linkage group selection: towards identifying genes controlling strain specific protective immunity in malaria. AB - Protective immunity against blood infections of malaria is partly specific to the genotype, or strain, of the parasites. The target antigens of Strain Specific Protective Immunity are expected, therefore, to be antigenically and genetically distinct in different lines of parasite. Here we describe the use of a genetic approach, Linkage Group Selection, to locate the target(s) of Strain Specific Protective Immunity in the rodent malaria parasite Plasmodium chabaudi chabaudi. In a previous such analysis using the progeny of a genetic cross between P. c. chabaudi lines AS-pyr1 and CB, a location on P. c. chabaudi chromosome 8 containing the gene for merozoite surface protein-1, a known candidate antigen for Strain Specific Protective Immunity, was strongly selected. P. c. chabaudi apical membrane antigen-1, another candidate for Strain Specific Protective Immunity, could not have been evaluated in this cross as AS-pyr1 and CB are identical within the cell surface domain of this protein. Here we use Linkage Group Selection analysis of Strain Specific Protective Immunity in a cross between P. c. chabaudi lines CB-pyr10 and AJ, in which merozoite surface protein 1 and apical membrane antigen-1 are both genetically distinct. In this analysis strain specific immune selection acted strongly on the region of P. c. chabaudi chromosome 8 encoding merozoite surface protein-1 and, less strongly, on the P. c. chabaudi chromosome 9 region encoding apical membrane antigen-1. The evidence from these two independent studies indicates that Strain Specific Protective Immunity in P. c. chabaudi in mice is mainly determined by a narrow region of the P. c. chabaudi genome containing the gene for the P. c. chabaudi merozoite surface protein-1 protein. Other regions, including that containing the gene for P. c. chabaudi apical membrane antigen-1, may be more weakly associated with Strain Specific Protective Immunity in these parasites. PMID- 17848989 TI - Structural and functional analyses of five conserved positively charged residues in the L1 and N-terminal DNA binding motifs of archaeal RADA protein. AB - RecA family proteins engage in an ATP-dependent DNA strand exchange reaction that includes a ssDNA nucleoprotein helical filament and a homologous dsDNA sequence. In spite of more than 20 years of efforts, the molecular mechanism of homology pairing and strand exchange is still not fully understood. Here we report a crystal structure of Sulfolobus solfataricus RadA overwound right-handed filament with three monomers per helical pitch. This structure reveals conformational details of the first ssDNA binding disordered loop (denoted L1 motif) and the dsDNA binding N-terminal domain (NTD). L1 and NTD together form an outwardly open palm structure on the outer surface of the helical filament. Inside this palm structure, five conserved basic amino acid residues (K27, K60, R117, R223 and R229) surround a 25 A pocket that is wide enough to accommodate anionic ssDNA, dsDNA or both. Biochemical analyses demonstrate that these five positively charged residues are essential for DNA binding and for RadA-catalyzed D-loop formation. We suggest that the overwound right-handed RadA filament represents a functional conformation in the homology search and pairing reaction. A new structural model is proposed for the homologous interactions between a RadA-ssDNA nucleoprotein filament and its dsDNA target. PMID- 17848990 TI - Intraepithelial and interstitial deposition of pathological prion protein in kidneys of scrapie-affected sheep. AB - Prions have been documented in extra-neuronal and extra-lymphatic tissues of humans and various ruminants affected by Transmissible Spongiform Encephalopathy (TSE). The presence of prion infectivity detected in cervid and ovine blood tempted us to reason that kidney, the organ filtrating blood derived proteins, may accumulate disease associated PrP(Sc). We collected and screened kidneys of experimentally, naturally scrapie-affected and control sheep for renal deposition of PrP(Sc) from distinct, geographically separated flocks. By performing Western blot, PET blot analysis and immunohistochemistry we found intraepithelial (cortex, medulla and papilla) and occasional interstitial (papilla) deposition of PrP(Sc )in kidneys of scrapie-affected sheep. Interestingly, glomerula lacked detectable signals indicative of PrP(Sc). PrP(Sc) was also detected in kidneys of subclinical sheep, but to significantly lower degree. Depending on the stage of the disease the incidence of PrP(Sc) in kidney varied from approximately 27% (subclinical) to 73.6% (clinical) in naturally scrapie-affected sheep. Kidneys from flocks without scrapie outbreak were devoid of PrP(Sc). Here we demonstrate unexpectedly frequent deposition of high levels of PrP(Sc) in ovine kidneys of various flocks. Renal deposition of PrP(Sc) is likely to be a pre-requisite enabling prionuria, a possible co-factor of horizontal prion-transmission in sheep. PMID- 17848991 TI - Early loss of Xist RNA expression and inactive X chromosome associated chromatin modification in developing primordial germ cells. AB - BACKGROUND: The inactive X chromosome characteristic of female somatic lineages is reactivated during development of the female germ cell lineage. In mouse, analysis of protein products of X-linked genes and/or transgenes located on the X chromosome has indicated that reactivation occurs after primordial germ cells reach the genital ridges. PRINCIPAL FINDINGS/METHODOLOGY: We present evidence that the epigenetic reprogramming of the inactive X-chromosome is initiated earlier than was previously thought, around the time that primordial germ cells (PGCs) migrate through the hindgut. Specifically, we find that Xist RNA expression, the primary signal for establishment of chromosome silencing, is extinguished in migrating PGCs. This is accompanied by displacement of Polycomb group repressor proteins Eed and Suz(12), and loss of the inactive X associated histone modification, methylation of histone H3 lysine 27. CONCLUSIONS/SIGNIFICANCE: We conclude that X reactivation in primordial germ cells occurs progressively, initiated by extinction of Xist RNA around the time that germ cells migrate through the hindgut to the genital ridges. The events that we observe are reminiscent of X reactivation of the paternal X chromosome in inner cell mass cells of mouse pre-implantation embryos and suggest a unified model in which execution of the pluripotency program represses Xist RNA thereby triggering progressive reversal of epigenetic silencing of the X chromosome. PMID- 17848992 TI - Declining rates in male circumcision amidst increasing evidence of its public health benefit. AB - BACKGROUND: Recent experimental evidence has demonstrated the benefits of male circumcision for the prevention of human immunodeficiency virus (HIV) infection. Studies have also shown that male circumcision is cost-effective and reduces the risk for certain ulcerative sexually transmitted diseases (STDs). The epidemiology of male circumcision in the United States is poorly studied and most prior reports were limited by self-reported measures. The study objective was to describe male circumcision trends among men attending the San Francisco municipal STD clinic, and to correlate the findings with HIV, syphilis and sexual orientation. METHODS AND FINDINGS: A cross sectional study was performed by reviewing all electronic records of males attending the San Francisco municipal STD clinic between 1996 and 2005. The prevalence of circumcision over time and by subpopulation such as race/ethnicity and sexual orientation were measured. The findings were further correlated with the presence of syphilis and HIV infection. Circumcision status was determined by physical examination and disease status by clinical evaluation with laboratory confirmation. Among 58,598 male patients, 32,613 (55.7%, 95% Confidence Interval (CI) 55.2-56.1) were circumcised. Male circumcision varied significantly by decade of birth (increasing between 1920 and 1950 and declining overall since the 1960's), race/ethnicity (Black: 62.2%, 95% CI 61.2-63.2, White: 60.0%, 95% CI 59.46-60.5, Asian Pacific Islander: 48.2%, 46.9-49.5 95% CI, and Hispanic: 42.2%, 95% CI 41.3-43.1), and sexual orientation (gay/bisexual: 73.0%, 95% CI 72.6-73.4; heterosexual: 66.0%, 65.5-66.5). Male circumcision may have been modestly protective against syphilis in HIV-uninfected heterosexual men (PR 0.92, 95% C.I. 0.83-1.02, P = 0.06). CONCLUSIONS: Male circumcision was common among men seeking STD services in San Francisco but has declined substantially in recent decades. Male circumcision rates differed by race/ethnicity and sexual orientation. Given recent studies suggesting the public health benefits of male circumcision, a reconsideration of national male circumcision policy is needed to respond to current trends. PMID- 17848993 TI - A fully automated robotic system for microinjection of zebrafish embryos. AB - As an important embodiment of biomanipulation, injection of foreign materials (e.g., DNA, RNAi, sperm, protein, and drug compounds) into individual cells has significant implications in genetics, transgenics, assisted reproduction, and drug discovery. This paper presents a microrobotic system for fully automated zebrafish embryo injection, which overcomes the problems inherent in manual operation, such as human fatigue and large variations in success rates due to poor reproducibility. Based on computer vision and motion control, the microrobotic system performs injection at a speed of 15 zebrafish embryos (chorion unremoved) per minute, with a survival rate of 98% (n = 350 embryos), a success rate of 99% (n = 350 embryos), and a phenotypic rate of 98.5% (n = 210 embryos). The sample immobilization technique and microrobotic control method are applicable to other biological injection applications such as the injection of mouse oocytes/embryos and Drosophila embryos to enable high-throughput biological and pharmaceutical research. PMID- 17848994 TI - Toll-like receptor expression and responsiveness of distinct murine splenic and mucosal B-cell subsets. AB - BACKGROUND: Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen associated molecular patterns and trigger innate immunity leading to initiation of adaptive immunity. TLR-mediated activation of dendritic cells (DCs) is known to be a critical event in the initiation of cellular and humoral immune responses. Recent work however suggests that B cells also express TLRs, and that they can be activated via TLR ligands. However, whether such B cell activation occurs only on memory B cells, or whether it can also occur on truly naive B cells remains controversial. Furthermore, the expression and functional relevance of TLRs on distinct subsets of B cells, which are known to play differential roles in humoral responses is not known. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the expression pattern of different TLRs in distinct subsets of murine B cells (naive, memory, follicular, marginal zone, B-1 and peyer's patch). In contrast to the reported restricted expression pattern of TLRs in human peripheral blood naive B cells, murine splenic naive B cells express a variety of TLRs with the exception of TLR5 and 8. Consistent with this relatively broad expression pattern, murine naive B cells proliferate and secrete antibody to a variety of TLR agonists in vitro, in the absence of B-cell receptor cross-linking. In addition, we observed subtle differences in the antibody secretion pattern of follicular, marginal zone, B-1 and peyer's patch B-cell subsets. CONCLUSIONS/SIGNIFICANCE: Thus various B cell subsets, including truly naive B cells, express multiple TLRs, and signaling via such TLRs results in their robust proliferation and antibody secretion, even in the absence of dendritic cell activation, or T-cell help. PMID- 17848995 TI - An amphioxus Gli gene reveals conservation of midline patterning and the evolution of hedgehog signalling diversity in chordates. AB - BACKGROUND: Hedgehog signalling, interpreted in receiving cells by Gli transcription factors, plays a central role in the development of vertebrate and Drosophila embryos. Many aspects of the signalling pathway are conserved between these lineages, however vertebrates have diverged in at least one key aspect: they have evolved multiple Gli genes encoding functionally-distinct proteins, increasing the complexity of the hedgehog-dependent transcriptional response. Amphioxus is one of the closest living relatives of the vertebrates, having split from the vertebrate lineage prior to the widespread gene duplication prominent in early vertebrate evolution. PRINCIPAL FINDINGS: We show that amphioxus has a single Gli gene, which is deployed in tissues adjacent to sources of hedgehog signalling derived from the midline and anterior endoderm. This shows the duplication and divergence of the Gli gene family, and hence the origin of vertebrate Gli functional diversity, was specific to the vertebrate lineage. However we also show that the single amphioxus Gli gene produces two distinct transcripts encoding different proteins. We utilise three tests of Gli function to examine the transcription regulatory capacities of these different proteins, demonstrating one has activating activity similar to Gli2, while the other acts as a weak repressor, similar to Gli3. CONCLUSIONS: These data show that vertebrates and amphioxus have evolved functionally-similar repertoires of Gli proteins using parallel molecular routes; vertebrates via gene duplication and divergence, and amphioxus via alternate splicing of a single gene. Our results demonstrate that similar functional complexity of intercellular signalling can be achieved via different evolutionary pathways. PMID- 17848996 TI - Nonassociative learning promotes respiratory entrainment to mechanical ventilation. AB - BACKGROUND: Patient-ventilator synchrony is a major concern in critical care and is influenced by phasic lung-volume feedback control of the respiratory rhythm. Routine clinical application of positive end-expiratory pressure (PEEP) introduces a tonic input which, if unopposed, might disrupt respiratory ventilator entrainment through sustained activation of the vagally-mediated Hering-Breuer reflex. We suggest that this potential adverse effect may be averted by two differentiator forms of nonassociative learning (habituation and desensitization) of the Hering-Breuer reflex via pontomedullary pathways. METHODOLOGY/PRINCIPAL FINDINGS: We tested these hypotheses in 17 urethane anesthetized adult Sprague-Dawley rats under controlled mechanical ventilation. Without PEEP, phrenic discharge was entrained 1:1 to the ventilator rhythm. Application of PEEP momentarily dampened the entrainment to higher ratios but this effect was gradually adapted by nonassociative learning. Bilateral electrolytic lesions of the pneumotaxic center weakened the adaptation to PEEP, whereas sustained stimulation of the pneumotaxic center weakened the entrainment independent of PEEP. In all cases, entrainment was abolished after vagotomy. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate an important functional role for pneumotaxic desensitization and extra-pontine habituation of the Hering Breuer reflex elicited by lung inflation: acting as buffers or high-pass filters against tonic vagal volume input, these differentiator forms of nonassociative learning help to restore respiratory-ventilator entrainment in the face of PEEP. Such central sites-specific habituation and desensitization of the Hering-Breuer reflex provide a useful experimental model of nonassociative learning in mammals that is of particular significance in understanding respiratory rhythmogenesis and coupled-oscillator entrainment mechanisms, and in the clinical management of mechanical ventilation in respiratory failure. PMID- 17848997 TI - Ubx regulates differential enlargement and diversification of insect hind legs. AB - Differential enlargement of hind (T3) legs represents one of the hallmarks of insect evolution. However, the actual mechanism(s) responsible are yet to be determined. To address this issue, we have now studied the molecular basis of T3 leg enlargement in Oncopeltus fasciatus (milkweed bug) and Acheta domesticus (house cricket). In Oncopeltus, the T3 tibia displays a moderate increase in size, whereas in Acheta, the T3 femur, tibia, and tarsus are all greatly enlarged. Here, we show that the hox gene Ultrabithorax (Ubx) is expressed in the enlarged segments of hind legs. Furthermore, we demonstrate that depletion of Ubx during embryogenesis has a primary effect in T3 legs and causes shortening of leg segments that are enlarged in a wild type. This result shows that Ubx is regulating the differential growth and enlargement of T3 legs in both Oncopeltus and Acheta. The emerging view suggests that Ubx was co-opted for a novel role in regulating leg growth and that the transcriptional modification of its expression may be a universal mechanism for the evolutionary diversification of insect hind legs. PMID- 17848998 TI - Sleep in the human hippocampus: a stereo-EEG study. AB - BACKGROUND: There is compelling evidence indicating that sleep plays a crucial role in the consolidation of new declarative, hippocampus-dependent memories. Given the increasing interest in the spatiotemporal relationships between cortical and hippocampal activity during sleep, this study aimed to shed more light on the basic features of human sleep in the hippocampus. METHODOLOGY/PRINCIPAL FINDINGS: We recorded intracerebral stereo-EEG directly from the hippocampus and neocortical sites in five epileptic patients undergoing presurgical evaluations. The time course of classical EEG frequency bands during the first three NREM-REM sleep cycles of the night was evaluated. We found that delta power shows, also in the hippocampus, the progressive decrease across sleep cycles, indicating that a form of homeostatic regulation of delta activity is present also in this subcortical structure. Hippocampal sleep was also characterized by: i) a lower relative power in the slow oscillation range during NREM sleep compared to the scalp EEG; ii) a flattening of the time course of the very low frequencies (up to 1 Hz) across sleep cycles, with relatively high levels of power even during REM sleep; iii) a decrease of power in the beta band during REM sleep, at odds with the typical increase of power in the cortical recordings. CONCLUSIONS/SIGNIFICANCE: Our data imply that cortical slow oscillation is attenuated in the hippocampal structures during NREM sleep. The most peculiar feature of hippocampal sleep is the increased synchronization of the EEG rhythms during REM periods. This state of resonance may have a supportive role for the processing/consolidation of memory. PMID- 17848999 TI - Successful biological invasion despite a severe genetic load. AB - Understanding the factors that influence the success of ecologically and economically damaging biological invasions is of prime importance. Recent studies have shown that invasive populations typically exhibit minimal, if any, reductions in genetic diversity, suggesting that large founding populations and/or multiple introductions are required for the success of biological invasions, consistent with predictions of the propagule pressure hypothesis. Through population genetic analysis of neutral microsatellite markers and a gene experiencing balancing selection, we demonstrate that the solitary bee Lasioglossum leucozonium experienced a single and severe bottleneck during its introduction from Europe. Paradoxically, the success of L. leucozonium in its introduced range occurred despite the severe genetic load caused by single-locus complementary sex-determination that still turns 30% of female-destined eggs into sterile diploid males, thereby substantially limiting the growth potential of the introduced population. Using stochastic modeling, we show that L. leucozonium invaded North America through the introduction of a very small number of propagules, most likely a singly-mated female. Our results suggest that chance events and ecological traits of invaders are more important than propagule pressure in determining invasion success, and that the vigilance required to prevent invasions may be considerably greater than has been previously considered. PMID- 17849000 TI - Crown plasticity and competition for canopy space: a new spatially implicit model parameterized for 250 North American tree species. AB - BACKGROUND: Canopy structure, which can be defined as the sum of the sizes, shapes and relative placements of the tree crowns in a forest stand, is central to all aspects of forest ecology. But there is no accepted method for deriving canopy structure from the sizes, species and biomechanical properties of the individual trees in a stand. Any such method must capture the fact that trees are highly plastic in their growth, forming tessellating crown shapes that fill all or most of the canopy space. METHODOLOGY/PRINCIPAL FINDINGS: We introduce a new, simple and rapidly-implemented model--the Ideal Tree Distribution, ITD--with tree form (height allometry and crown shape), growth plasticity, and space-filling, at its core. The ITD predicts the canopy status (in or out of canopy), crown depth, and total and exposed crown area of the trees in a stand, given their species, sizes and potential crown shapes. We use maximum likelihood methods, in conjunction with data from over 100,000 trees taken from forests across the coterminous US, to estimate ITD model parameters for 250 North American tree species. With only two free parameters per species--one aggregate parameter to describe crown shape, and one parameter to set the so-called depth bias--the model captures between-species patterns in average canopy status, crown radius, and crown depth, and within-species means of these metrics vs stem diameter. The model also predicts much of the variation in these metrics for a tree of a given species and size, resulting solely from deterministic responses to variation in stand structure. CONCLUSIONS/SIGNIFICANCE: This new model, with parameters for US tree species, opens up new possibilities for understanding and modeling forest dynamics at local and regional scales, and may provide a new way to interpret remote sensing data of forest canopies, including LIDAR and aerial photography. PMID- 17849001 TI - Retinal encoding of ultrabrief shape recognition cues. AB - Shape encoding mechanisms can be probed by the sequential brief display of dots that mark the boundary of the shape, and delays of less that a millisecond between successive dots can impair recognition. It is not entirely clear whether this is accomplished by preserving stimulus timing in the signal being sent to the brain, or calls for a retinal binding mechanism. Two experiments manipulated the degree of simultaneity among and within dot pairs, requiring also that the pair members be in the same half of the visual field or on opposite halves, i.e., across the midline from one another. Recognition performance was impaired the same for these two conditions. The results make it likely that simultaneity of cues is being registered within the retina. A potential mechanism is suggested, calling for linkage of stimulated sites through activation of PA1 cells. A third experiment confirmed a prior finding that the overall level of recognition deficit is partly a function of display-set size, and affirmed submillisecond resolution in binding dot pairs into effective shape-recognition cues. PMID- 17849002 TI - Conceptual modeling in systems biology fosters empirical findings: the mRNA lifecycle. AB - One of the main obstacles to understanding complex biological systems is the extent and rapid evolution of information, way beyond the capacity individuals to manage and comprehend. Current modeling approaches and tools lack adequate capacity to model concurrently structure and behavior of biological systems. Here we propose Object-Process Methodology (OPM), a holistic conceptual modeling paradigm, as a means to model both diagrammatically and textually biological systems formally and intuitively at any desired number of levels of detail. OPM combines objects, e.g., proteins, and processes, e.g., transcription, in a way that is simple and easily comprehensible to researchers and scholars. As a case in point, we modeled the yeast mRNA lifecycle. The mRNA lifecycle involves mRNA synthesis in the nucleus, mRNA transport to the cytoplasm, and its subsequent translation and degradation therein. Recent studies have identified specific cytoplasmic foci, termed processing bodies that contain large complexes of mRNAs and decay factors. Our OPM model of this cellular subsystem, presented here, led to the discovery of a new constituent of these complexes, the translation termination factor eRF3. Association of eRF3 with processing bodies is observed after a long-term starvation period. We suggest that OPM can eventually serve as a comprehensive evolvable model of the entire living cell system. The model would serve as a research and communication platform, highlighting unknown and uncertain aspects that can be addressed empirically and updated consequently while maintaining consistency. PMID- 17849003 TI - Brain expressed microRNAs implicated in schizophrenia etiology. AB - BACKGROUND: Protein encoding genes have long been the major targets for research in schizophrenia genetics. However, with the identification of regulatory microRNAs (miRNAs) as important in brain development and function, miRNAs genes have emerged as candidates for schizophrenia-associated genetic factors. Indeed, the growing understanding of the regulatory properties and pleiotropic effects that miRNA have on molecular and cellular mechanisms, suggests that alterations in the interactions between miRNAs and their mRNA targets may contribute to phenotypic variation. METHODOLOGY/PRINCIPAL FINDINGS: We have studied the association between schizophrenia and genetic variants of miRNA genes associated with brain-expression using a case-control study design on three Scandinavian samples. Eighteen known SNPs within or near brain-expressed miRNAs in three samples (Danish, Swedish and Norwegian: 420/163/257 schizophrenia patients and 1006/177/293 control subjects), were analyzed. Subsequently, joint analysis of the three samples was performed on SNPs showing marginal association. Two SNPs rs17578796 and rs1700 in hsa-mir-206 (mir-206) and hsa-mit-198 (mir-198) showed nominal significant allelic association to schizophrenia in the Danish and Norwegian sample respectively (P = 0.0021 & p = 0.038), of which only rs17578796 was significant in the joint sample. In-silico analysis revealed that 8 of the 15 genes predicted to be regulated by both mir-206 and mir-198, are transcriptional targets or interaction partners of the JUN, ATF2 and TAF1 connected in a tight network. JUN and two of the miRNA targets (CCND2 and PTPN1) in the network have previously been associated with schizophrenia. CONCLUSIONS/SIGNIFICANCE: We found nominal association between brain-expressed miRNAs and schizophrenia for rs17578796 and rs1700 located in mir-206 and mir-198 respectively. These two miRNAs have a surprising large number (15) of targets in common, eight of which are also connected by the same transcription factors. PMID- 17849004 TI - Discovery of genes activated by the mitochondrial unfolded protein response (mtUPR) and cognate promoter elements. AB - In an accompanying paper, we show that the mitochondrial Unfolded Protein Response or mtUPR is initiated by the activation of transcription of chop through an AP-1 element in the chop promoter. Further, we show that the c/ebp beta gene is similarly activated and CHOP and C/EBP beta subsequently hetero-dimerise to activate transcription of mtUPR responsive genes. Here, we report the discovery of six additional mtUPR responsive genes. We found that these genes encoding mitochondrial proteases YME1L1 and MPP beta, import component Tim17A and enzymes NDUFB2, endonuclease G and thioredoxin 2, all contain a CHOP element in their promoters. In contrast, genes encoding mitochondrial proteins Afg3L2, Paraplegin, Lon and SAM 50, which do not have a CHOP element, were not up-regulated. Conversely, genes with CHOP elements encoding cytosolic proteins were not induced by the accumulation of unfolded proteins in mitochondria. These results indicate that mtUPR responsive genes appear to share a requirement for a CHOP element, but that this is not sufficient for the regulation of the mtUPR. A more detailed analysis of promoters of mtUPR responsive genes revealed at least two additional highly conserved, putative regulatory sites either side of the CHOP element, one a motif of 12 bp which lies 14 bp upstream of the CHOP site and another 9 bp element, 2 bp downstream of the CHOP site. Both of these additional elements are conserved in the promoters of 9 of the ten mtUPR responsive genes we have identified so far, the exception being the Cpn60/10 bidirectional promoter. Mutation of each of these elements substantially reduced the mtUPR responsiveness of the promoters suggesting that these elements coordinately regulate mtUPR. PMID- 17849005 TI - Intra-organ variation in age-related mutation accumulation in the mouse. AB - Using a transgenic mouse model harboring chromosomally integrated lacZ mutational target genes, we previously demonstrated that mutations accumulate with age much more rapidly in the small intestine than in the brain. Here it is shown that in the small intestine point mutations preferentially accumulate in epithelial cells of the mucosa scraped off the underlying serosa. The mucosal cells are the differentiated villus cells that have undergone multiple cell divisions. A smaller age-related increase, also involving genome rearrangements, was observed in the serosa, which consists mainly of the remaining crypts and non-dividing smooth muscle cells. In the brain we observed an accumulation of only point mutations in no other areas than hypothalamus and hippocampus. To directly test for cell division as the determining factor in the generation of point mutations we compared mutation induction between mitotically active and quiescent embryonic fibroblasts from the same lacZ mice, treated with either UV (a point mutagen) or hydrogen peroxide (a clastogen). The results indicate that while point mutations are highly replication-dependent, genome rearrangements are as easily induced in non-dividing cells as in mitotically active ones. This strongly suggests that the point mutations found to have accumulated in the mucosal part of the small intestine are the consequence of replication errors. The same is likely true for point mutations accumulating in hippocampus and hypothalamus of the brain since neurogenesis in these two areas continues throughout life. The observed intra organ variation in mutation susceptibility as well as the variation in replication dependency of different types of mutations indicates the need to not only extend observations made on whole organs to their sub-structures but also take the type of mutations and mitotic activity of the cells into consideration. This should help elucidating the impact of genome instability and its consequences on aging and disease. PMID- 17849006 TI - An all-atom model of the chromatin fiber containing linker histones reveals a versatile structure tuned by the nucleosomal repeat length. AB - In the nucleus of eukaryotic cells, histone proteins organize the linear genome into a functional and hierarchical architecture. In this paper, we use the crystal structures of the nucleosome core particle, B-DNA and the globular domain of H5 linker histone to build the first all-atom model of compact chromatin fibers. In this 3D jigsaw puzzle, DNA bending is achieved by solving an inverse kinematics problem. Our model is based on recent electron microscopy measurements of reconstituted fiber dimensions. Strikingly, we find that the chromatin fiber containing linker histones is a polymorphic structure. We show that different fiber conformations are obtained by tuning the linker histone orientation at the nucleosomes entry/exit according to the nucleosomal repeat length. We propose that the observed in vivo quantization of nucleosomal repeat length could reflect nature's ability to use the DNA molecule's helical geometry in order to give chromatin versatile topological and mechanical properties. PMID- 17849008 TI - Dating phylogenies with hybrid local molecular clocks. AB - BACKGROUND: Because rates of evolution and species divergence times cannot be estimated directly from molecular data, all current dating methods require that specific assumptions be made before inferring any divergence time. These assumptions typically bear either on rates of molecular evolution (molecular clock hypothesis, local clocks models) or on both rates and times (penalized likelihood, Bayesian methods). However, most of these assumptions can affect estimated dates, oftentimes because they underestimate large amounts of rate change. PRINCIPAL FINDINGS: A significant modification to a recently proposed ad hoc rate-smoothing algorithm is described, in which local molecular clocks are automatically placed on a phylogeny. This modification makes use of hybrid approaches that borrow from recent theoretical developments in microarray data analysis. An ad hoc integration of phylogenetic uncertainty under these local clock models is also described. The performance and accuracy of the new methods are evaluated by reanalyzing three published data sets. CONCLUSIONS: It is shown that the new maximum likelihood hybrid methods can perform better than penalized likelihood and almost as well as uncorrelated Bayesian models. However, the new methods still tend to underestimate the actual amount of rate change. This work demonstrates the difficulty of estimating divergence times using local molecular clocks. PMID- 17849007 TI - Comparative expression profiling of the Chlamydia trachomatis pmp gene family for clinical and reference strains. AB - BACKGROUND: Chlamydia trachomatis, an obligate intracellular pathogen, is a leading worldwide cause of ocular and urogenital diseases. Advances have been made in our understanding of the nine-member polymorphic membrane protein (Pmp) gene (pmp) family of C. trachomatis. However, there is only limited information on their biologic role, especially for biological variants (biovar) and clinical strains. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated expression for pmps throughout development for reference strains E/Bour and L2/434, representing different biovars, and for clinical E and L2 strains. Immunoreactivity of patient sera to recombinant (r)Pmps was also determined. All pmps were expressed at two hours. pmpA had the lowest expression but was up-regulated at 12 h for all strains, indicating involvement in reticulate body development. For pmpD, expression peaked at 36 h. Additionally, 57.7% of sera from infected and 0% from uninfected adolescents were reactive to rPmpD (p = 0.001), suggesting a role in immunogenicity. pmpF had the highest expression levels for all clinical strains and L2/434 with differential expression of the pmpFE operon for the same strains. Sera were nonreactive to rPmpF despite immunoreactivity to rMOMP and rPmpD, suggesting that PmpF is not associated with humoral immune responses. pmpFE sequences for clinical strains were identical to those of the respective reference strains. We identified the putative pmpFE promoter, which was, surprisingly, 100% conserved for all strains. Analyses of ribosomal binding sites, RNase E, and hairpin structures suggested complex regulatory mechanism(s) for this >6 Kb operon. CONCLUSIONS/SIGNIFICANCE: The dissimilar expression of the same pmp for different C. trachomatis strains may explain different strain specific needs and phenotypic distinctions. This is further supported by the differential immunoreactivity to rPmpD and rPmpF of sera from patients infected with different strains. Furthermore, clinical E strains did not correlate with the E reference strain at the gene expression level, reinforcing the need for expansive studies of clinical strains. PMID- 17849009 TI - Automated builder and database of protein/membrane complexes for molecular dynamics simulations. AB - Molecular dynamics simulations of membrane proteins have provided deeper insights into their functions and interactions with surrounding environments at the atomic level. However, compared to solvation of globular proteins, building a realistic protein/membrane complex is still challenging and requires considerable experience with simulation software. Membrane Builder in the CHARMM-GUI website (http://www.charmm-gui.org) helps users to build such a complex system using a web browser with a graphical user interface. Through a generalized and automated building process including system size determination as well as generation of lipid bilayer, pore water, bulk water, and ions, a realistic membrane system with virtually any kinds and shapes of membrane proteins can be generated in 5 minutes to 2 hours depending on the system size. Default values that were elaborated and tested extensively are given in each step to provide reasonable options and starting points for both non-expert and expert users. The efficacy of Membrane Builder is illustrated by its applications to 12 transmembrane and 3 interfacial membrane proteins, whose fully equilibrated systems with three different types of lipid molecules (DMPC, DPPC, and POPC) and two types of system shapes (rectangular and hexagonal) are freely available on the CHARMM-GUI website. One of the most significant advantages of using the web environment is that, if a problem is found, users can go back and re-generate the whole system again before quitting the browser. Therefore, Membrane Builder provides the intuitive and easy way to build and simulate the biologically important membrane system. PMID- 17849010 TI - Metabolome based reaction graphs of M. tuberculosis and M. leprae: a comparative network analysis. AB - BACKGROUND: Several types of networks, such as transcriptional, metabolic or protein-protein interaction networks of various organisms have been constructed, that have provided a variety of insights into metabolism and regulation. Here, we seek to exploit the reaction-based networks of three organisms for comparative genomics. We use concepts from spectral graph theory to systematically determine how differences in basic metabolism of organisms are reflected at the systems level and in the overall topological structures of their metabolic networks. METHODOLOGY/PRINCIPAL FINDINGS: Metabolome-based reaction networks of Mycobacterium tuberculosis, Mycobacterium leprae and Escherichia coli have been constructed based on the KEGG LIGAND database, followed by graph spectral analysis of the network to identify hubs as well as the sub-clustering of reactions. The shortest and alternate paths in the reaction networks have also been examined. Sub-cluster profiling demonstrates that reactions of the mycolic acid pathway in mycobacteria form a tightly connected sub-cluster. Identification of hubs reveals reactions involving glutamate to be central to mycobacterial metabolism, and pyruvate to be at the centre of the E. coli metabolome. The analysis of shortest paths between reactions has revealed several paths that are shorter than well established pathways. CONCLUSIONS: We conclude that severe downsizing of the leprae genome has not significantly altered the global structure of its reaction network but has reduced the total number of alternate paths between its reactions while keeping the shortest paths between them intact. The hubs in the mycobacterial networks that are absent in the human metabolome can be explored as potential drug targets. This work demonstrates the usefulness of constructing metabolome based networks of organisms and the feasibility of their analyses through graph spectral methods. The insights obtained from such studies provide a broad overview of the similarities and differences between organisms, taking comparative genomics studies to a higher dimension. PMID- 17849011 TI - Role of ENPP1 on adipocyte maturation. AB - BACKGROUND: It is recognized that the ability of adipose tissue to expand in response to energy excess, i.e. adipocyte maturation, is important in determining systemic abnormalities in glucose and lipid metabolism. Ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1, also known as PC-1) has been recently reported to be involved in the pathogenesis of insulin resistance and related diseases. However, its role on adipose tissue physiology as a mechanism of systemic insulin resistance is not understood. This study was performed to evaluate whether ENPP1 is regulated during adipogenesis and whether over expression in adipocytes can affect adipocyte maturation, a potential novel mechanism of ENPP1-related insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: ENPP1 expression was found down-regulated during 3T3-L1 maturation, and over expression of human ENPP1 in 3T3-L1 (pQCXIP-ENPP1 vector) resulted in adipocyte insulin resistance and in defective adipocyte maturation. Adipocyte maturation was more efficient in mesenchymal embryonal cells from ENPP1 knockout mice than from wild-type. CONCLUSIONS: We identify ENPP1 as a novel mechanism of defective adipocyte maturation. This mechanism could contribute to the pathogenesis of insulin resistance in absence of obesity. PMID- 17849012 TI - Self-referential cognition and empathy in autism. AB - BACKGROUND: Individuals with autism spectrum conditions (ASC) have profound impairments in the interpersonal social domain, but it is unclear if individuals with ASC also have impairments in the intrapersonal self-referential domain. We aimed to evaluate across several well validated measures in both domains, whether both self-referential cognition and empathy are impaired in ASC and whether these two domains are related to each other. METHODOLOGY/PRINCIPAL FINDINGS: Thirty adults aged 19-45, with Asperger Syndrome or high-functioning autism and 30 age, sex, and IQ matched controls participated in the self-reference effect (SRE) paradigm. In the SRE paradigm, participants judged adjectives in relation to the self, a similar close other, a dissimilar non-close other, or for linguistic content. Recognition memory was later tested. After the SRE paradigm, several other complimentary self-referential cognitive measures were taken. Alexithymia and private self-consciousness were measured via self-report. Self-focused attention was measured on the Self-Focus Sentence Completion task. Empathy was measured with 3 self-report instruments and 1 performance measure of mentalizing (Eyes test). Self-reported autistic traits were also measured with the Autism Spectrum Quotient (AQ). Although individuals with ASC showed a significant SRE in memory, this bias was decreased compared to controls. Individuals with ASC also showed reduced memory for the self and a similar close other and also had concurrent impairments on measures of alexithymia, self-focused attention, and on all 4 empathy measures. Individual differences in self-referential cognition predicted mentalizing ability and self-reported autistic traits. More alexithymia and less self memory was predictive of larger mentalizing impairments and AQ scores regardless of diagnosis. In ASC, more self-focused attention is associated with better mentalizing ability and lower AQ scores, while in controls, more self focused attention is associated with decreased mentalizing ability and higher AQ scores. Increasing private self-consciousness also predicted better mentalizing ability, but only for individuals with ASC. CONCLUSIONS/SIGNIFICANCE: We conclude that individuals with ASC have broad impairments in both self-referential cognition and empathy. These two domains are also intrinsically linked and support predictions made by simulation theory. Our results also highlight a specific dysfunction in ASC within cortical midlines structures of the brain such as the medial prefrontal cortex. PMID- 17849013 TI - Degeneration of the olfactory guanylyl cyclase D gene during primate evolution. AB - BACKGROUND: The mammalian olfactory system consists of several subsystems that detect specific sets of chemical cues and underlie a variety of behavioral responses. Within the main olfactory epithelium at least three distinct types of chemosensory neurons can be defined by their expression of unique sets of signal transduction components. In rodents, one set of neurons expresses the olfactory specific guanylyl cyclase (GC)-D gene (Gucy2d, guanylyl cyclase 2d) and other cell-type specific molecules. GC-D-positive neurons project their axons to a small group of atypical "necklace" glomeruli in the olfactory bulb, some of which are activated in response to suckling in neonatal rodents and to atmospheric CO2 in adult mice. Because GC-D is a pseudogene in humans, signaling through this system appears to have been lost at some point in primate evolution. PRINCIPAL FINDINGS: Here we used a combination of bioinformatic analysis of trace-archive and genome-assembly data and sequencing of PCR-amplified genomic DNA to determine when during primate evolution the functional gene was lost. Our analysis reveals that GC-D is a pseudogene in a large number of primate species, including apes, Old World and New World monkeys and tarsier. In contrast, the gene appears intact and has evolved under purifying selection in mouse, rat, dog, lemur and bushbaby. CONCLUSIONS: These data suggest that signaling through GC-D-expressing cells was probably compromised more than 40 million years ago, prior to the divergence of New World monkeys from Old World monkeys and apes, and thus cannot be involved in chemosensation in most primates. PMID- 17849014 TI - Molecular and structural discrimination of proline racemase and hydroxyproline-2 epimerase from nosocomial and bacterial pathogens. AB - The first eukaryotic proline racemase (PRAC), isolated from the human Trypanosoma cruzi pathogen, is a validated therapeutic target against Chagas' disease. This essential enzyme is implicated in parasite life cycle and infectivity and its ability to trigger host B-cell nonspecific hypergammaglobulinemia contributes to parasite evasion and persistence. Using previously identified PRAC signatures and data mining we present the identification and characterization of a novel PRAC and five hydroxyproline epimerases (HyPRE) from pathogenic bacteria. Single mutation of key HyPRE catalytic cysteine abrogates enzymatic activity supporting the presence of two reaction centers per homodimer. Furthermore, evidences are provided that Brucella abortus PrpA [for 'proline racemase' virulence factor A] and homologous proteins from two Brucella spp are bona fide HyPREs and not 'one way' directional PRACs as described elsewhere. Although the mechanisms of aminoacid racemization and epimerization are conserved between PRAC and HyPRE, our studies demonstrate that substrate accessibility and specificity partly rely on constraints imposed by aromatic or aliphatic residues distinctively belonging to the catalytic pockets. Analysis of PRAC and HyPRE sequences along with reaction center structural data disclose additional valuable elements for in silico discrimination of the enzymes. Furthermore, similarly to PRAC, the lymphocyte mitogenicity displayed by HyPREs is discussed in the context of bacterial metabolism and pathogenesis. Considering tissue specificity and tropism of infectious pathogens, it would not be surprising if upon infection PRAC and HyPRE play important roles in the regulation of the intracellular and extracellular amino acid pool profiting the microrganism with precursors and enzymatic pathways of the host. PMID- 17849015 TI - Chimpanzees share forbidden fruit. AB - The sharing of wild plant foods is infrequent in chimpanzees, but in chimpanzee communities that engage in hunting, meat is frequently used as a 'social tool' for nurturing alliances and social bonds. Here we report the only recorded example of regular sharing of plant foods by unrelated, non-provisioned wild chimpanzees, and the contexts in which these sharing behaviours occur. From direct observations, adult chimpanzees at Bossou (Republic of Guinea, West Africa) very rarely transferred wild plant foods. In contrast, they shared cultivated plant foods much more frequently (58 out of 59 food sharing events). Sharing primarily consists of adult males allowing reproductively cycling females to take food that they possess. We propose that hypotheses focussing on 'food-for sex and -grooming' and 'showing-off' strategies plausibly account for observed sharing behaviours. A changing human-dominated landscape presents chimpanzees with fresh challenges, and our observations suggest that crop-raiding provides adult male chimpanzees at Bossou with highly desirable food commodities that may be traded for other currencies. PMID- 17849016 TI - Age- and sex-specific mortality patterns in an emerging wildlife epidemic: the phocine distemper in European harbour seals. AB - Analyses of the dynamics of diseases in wild populations typically assume all individuals to be identical. However, profound effects on the long-term impact on the host population can be expected if the disease has age and sex dependent dynamics. The Phocine Distemper Virus (PDV) caused two mass mortalities in European harbour seals in 1988 and in 2002. We show the mortality patterns were highly age specific on both occasions, where young of the year and adult (>4 yrs) animals suffered extremely high mortality, and sub-adult seals (1-3 yrs) of both sexes experienced low mortality. Consequently, genetic differences cannot have played a main role explaining why some seals survived and some did not in the study region, since parents had higher mortality levels than their progeny. Furthermore, there was a conspicuous absence of animals older than 14 years among the victims in 2002, which strongly indicates that the survivors from the previous disease outbreak in 1988 had acquired and maintained immunity to PDV. These specific mortality patterns imply that contact rates and susceptibility to the disease are strongly age and sex dependent variables, underlining the need for structured epidemic models for wildlife diseases. Detailed data can thus provide crucial information about a number of vital parameters such as functional herd immunity. One of many future challenges in understanding the epidemiology of the PDV and other wildlife diseases is to reveal how immune system responses differ among animals in different stages during their life cycle. The influence of such underlying mechanisms may also explain the limited evidence for abrupt disease thresholds in wild populations. PMID- 17849017 TI - Robust off- and online separation of intracellularly recorded up and down cortical states. AB - BACKGROUND: The neuronal cortical network generates slow (<1 Hz) spontaneous rhythmic activity that emerges from the recurrent connectivity. This activity occurs during slow wave sleep or anesthesia and also in cortical slices, consisting of alternating up (active, depolarized) and down (silent, hyperpolarized) states. The search for the underlying mechanisms and the possibility of analyzing network dynamics in vitro has been subject of numerous studies. This exposes the need for a detailed quantitative analysis of the membrane fluctuating behavior and computerized tools to automatically characterize the occurrence of up and down states. METHODOLOGY/PRINCIPAL FINDINGS: Intracellular recordings from different areas of the cerebral cortex were obtained from both in vitro and in vivo preparations during slow oscillations. A method that separates up and down states recorded intracellularly is defined and analyzed here. The method exploits the crossover of moving averages, such that transitions between up and down membrane regimes can be anticipated based on recent and past voltage dynamics. We demonstrate experimentally the utility and performance of this method both offline and online, the online use allowing to trigger stimulation or other events in the desired period of the rhythm. This technique is compared with a histogram-based approach that separates the states by establishing one or two discriminating membrane potential levels. The robustness of the method presented here is tested on data that departs from highly regular alternating up and down states. CONCLUSIONS/SIGNIFICANCE: We define a simple method to detect cortical states that can be applied in real time for offline processing of large amounts of recorded data on conventional computers. Also, the online detection of up and down states will facilitate the study of cortical dynamics. An open-source MATLAB toolbox, and Spike 2-compatible version are made freely available. PMID- 17849018 TI - Impedance-matching hearing in Paleozoic reptiles: evidence of advanced sensory perception at an early stage of amniote evolution. AB - BACKGROUND: Insights into the onset of evolutionary novelties are key to the understanding of amniote origins and diversification. The possession of an impedance-matching tympanic middle ear is characteristic of all terrestrial vertebrates with a sophisticated hearing sense and an adaptively important feature of many modern terrestrial vertebrates. Whereas tympanic ears seem to have evolved multiple times within tetrapods, especially among crown-group members such as frogs, mammals, squamates, turtles, crocodiles, and birds, the presence of true tympanic ears has never been recorded in a Paleozoic amniote, suggesting they evolved fairly recently in amniote history. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we performed a morphological examination and a phylogenetic analysis of poorly known parareptiles from the Middle Permian of the Mezen River Basin in Russia. We recovered a well-supported clade that is characterized by a unique cheek morphology indicative of a tympanum stretching across large parts of the temporal region to an extent not seen in other amniotes, fossil or extant, and a braincase specialized in showing modifications clearly related to an increase in auditory function, unlike the braincase of any other Paleozoic tetrapod. In addition, we estimated the ratio of the tympanum area relative to the stapedial footplate for the basalmost taxon of the clade, which, at 23:1, is in close correspondence to that of modern amniotes capable of efficient impedance-matching hearing. CONCLUSIONS/SIGNIFICANCE: Using modern amniotes as analogues, the possession of an impedance-matching middle ear in these parareptiles suggests unique ecological adaptations potentially related to living in dim-light environments. More importantly, our results demonstrate that already at an early stage of amniote diversification, and prior to the Permo Triassic extinction event, the complexity of terrestrial vertebrate ecosystems had reached a level that proved advanced sensory perception to be of notable adaptive significance. PMID- 17849019 TI - Cross-modal object recognition is viewpoint-independent. AB - BACKGROUND: Previous research suggests that visual and haptic object recognition are viewpoint-dependent both within- and cross-modally. However, this conclusion may not be generally valid as it was reached using objects oriented along their extended y-axis, resulting in differential surface processing in vision and touch. In the present study, we removed this differential by presenting objects along the z-axis, thus making all object surfaces more equally available to vision and touch. METHODOLOGY/PRINCIPAL FINDINGS: Participants studied previously unfamiliar objects, in groups of four, using either vision or touch. Subsequently, they performed a four-alternative forced-choice object identification task with the studied objects presented in both unrotated and rotated (180 degrees about the x-, y-, and z-axes) orientations. Rotation impaired within-modal recognition accuracy in both vision and touch, but not cross-modal recognition accuracy. Within-modally, visual recognition accuracy was reduced by rotation about the x- and y-axes more than the z-axis, whilst haptic recognition was equally affected by rotation about all three axes. Cross-modal (but not within-modal) accuracy correlated with spatial (but not object) imagery scores. CONCLUSIONS/SIGNIFICANCE: The viewpoint-independence of cross-modal object identification points to its mediation by a high-level abstract representation. The correlation between spatial imagery scores and cross-modal performance suggest that construction of this high-level representation is linked to the ability to perform spatial transformations. Within-modal viewpoint dependence appears to have a different basis in vision than in touch, possibly due to surface occlusion being important in vision but not touch. PMID- 17849020 TI - No language-specific activation during linguistic processing of observed actions. AB - BACKGROUND: It has been suggested that cortical neural systems for language evolved from motor cortical systems, in particular from those fronto-parietal systems responding also to action observation. While previous studies have shown shared cortical systems for action--or action observation--and language, they did not address the question of whether linguistic processing of visual stimuli occurs only within a subset of fronto-parietal areas responding to action observation. If this is true, the hypothesis that language evolved from fronto parietal systems matching action execution and action observation would be strongly reinforced. METHODOLOGY/ PRINCIPAL FINDINGS: We used functional magnetic resonance imaging (fMRI) while subjects watched video stimuli of hand-object interactions and control photo stimuli of the objects and performed linguistic (conceptual and phonological), and perceptual tasks. Since stimuli were identical for linguistic and perceptual tasks, differential activations had to be related to task demands. The results revealed that the linguistic tasks activated left inferior frontal areas that were subsets of a large bilateral fronto-parietal network activated during action perception. Not a single cortical area demonstrated exclusive--or even simply higher--activation for the linguistic tasks compared to the action perception task. CONCLUSIONS: These results show that linguistic tasks do not only share common neural representations but essentially activate a subset of the action observation network if identical stimuli are used. Our findings strongly support the evolutionary hypothesis that fronto-parietal systems matching action execution and observation were co-opted for language, a process known as exaptation. PMID- 17849021 TI - Evidence for paternal leakage in hybrid periodical cicadas (Hemiptera: Magicicada spp.). AB - Mitochondrial inheritance is generally assumed to be maternal. However, there is increasing evidence of exceptions to this rule, especially in hybrid crosses. In these cases, mitochondria are also inherited paternally, so "paternal leakage" of mitochondria occurs. It is important to understand these exceptions better, since they potentially complicate or invalidate studies that make use of mitochondrial markers. We surveyed F1 offspring of experimental hybrid crosses of the 17-year periodical cicadas Magicicada septendecim, M. septendecula, and M. cassini for the presence of paternal mitochondrial markers at various times during development (1-day eggs; 3-, 6-, 9-week eggs; 16-month old 1st and 2nd instar nymphs). We found evidence of paternal leakage in both reciprocal hybrid crosses in all of these samples. The relative difficulty of detecting paternal mtDNA in the youngest eggs and ease of detecting leakage in older eggs and in nymphs suggests that paternal mitochondria proliferate as the eggs develop. Our data support recent theoretical predictions that paternal leakage may be more common than previously estimated. PMID- 17849023 TI - Professionalism and conflict of interest in new technology introduction. PMID- 17849022 TI - The restriction of zoonotic PERV transmission by human APOBEC3G. AB - The human APOBEC3G protein is an innate anti-viral factor that can dominantly inhibit the replication of some endogenous and exogenous retroviruses. The prospects of purposefully harnessing such an anti-viral defense are under investigation. Here, long-term co-culture experiments were used to show that porcine endogenous retrovirus (PERV) transmission from pig to human cells is reduced to nearly undetectable levels by expressing human APOBEC3G in virus producing pig kidney cells. Inhibition occurred by a deamination-independent mechanism, likely after particle production but before the virus could immortalize by integration into human genomic DNA. PERV inhibition did not require the DNA cytosine deaminase activity of APOBEC3G and, correspondingly, APOBEC3G-attributable hypermutations were not detected. In contrast, over expression of the sole endogenous APOBEC3 protein of pigs failed to interfere significantly with PERV transmission. Together, these data constitute the first proof-of-principle demonstration that APOBEC3 proteins can be used to fortify the innate anti-viral defenses of cells to prevent the zoonotic transmission of an endogenous retrovirus. These studies suggest that human APOBEC3G-transgenic pigs will provide safer, PERV-less xenotransplantation resources and that analogous cross-species APOBEC3-dependent restriction strategies may be useful for thwarting other endogenous as well as exogenous retrovirus infections. PMID- 17849024 TI - Rheumatoid arthritis in the cervical spine: what you need to know. PMID- 17849025 TI - FDA medical device approval: things you didn't learn in medical school or residency. AB - The Food and Drug Administration (FDA) does more than regulate food and drug products. Through its medical device evaluation process, FDA affects every orthopedic surgeon's practice and every orthopedic patient every day. FDA regulations affect the development of each orthopedic device in some way, from the product's inception to its senescence, but the regulatory process and what the FDA's stamp of approval means are not part of the curriculum in medical school or residency. Each device follows a specific pathway from manufacture to physician use and patient care depending on the assessment of risk associated with the device or classes of devices. The evaluation of safety and effectiveness involves a complex process of biomechanical, engineering, preclinical, laboratory, clinical, and epidemiological assessment. How different types of devices get to the patient are reviewed, and the basics of the regulatory process are explained in this paper. Common myths are set straight, and FDA's concerns with "off-label" use are discussed. The role of the orthopedic surgeon in the regulatory process is also introduced. PMID- 17849026 TI - Advances in technology and surgical technique in spine surgery. AB - This comprehensive review article encompasses a broad variety of topics within the spinal literature and includes an update on the latest technology and techniques for the spine. PMID- 17849027 TI - Characterization of graft subsidence in anterior cervical discectomy and fusion with rigid anterior plate fixation. AB - This study addressed radiographically the evaluation, presence, location, and degree of subsidence with secondary focus on the various clinical parameters and outcomes in 32 patients who underwent anterior cervical discectomy and fusion (ACDF) with tricortical iliac crest bone grafts and rigid anterior plate fixation. Postoperative follow-up plain radiographs were evaluated to determine subsidence on lateral neutral images by measuring the change in height of interscrew distance (ISD) and anterior (AVD), mid (MVD), and posterior (PVD) vertebral endplate-to-endplate vertical distances. Clinical functional outcome and various risk factors were also addressed. A 100% fusion rate was achieved, no instrumentation-related complications were noted, and mild graft subsidence occurred in each patient after the initial 2 months of surgery. Mean AVD, MVD, and PVD were 1.2 mm, 0.4 mm and 0.6 mm, respectively. Mean ISD was 0.6 mm. Percent change for AVD, MVD, PVD, and ISD was 2.3%, 0.8%, 1.2%, and 1.2%, respectively. Subsidence was more pronounced at the anterior vertebral graft endplate interface (P < .05). Satisfactory clinical results were reported in 90.9% of the patients. With such a sample size, age, sex, smoking status, plate design, graft type, and operative or number of fused levels did not demonstrate statistically significant differences to the degree of subsidence. This paper has shown that ACDF with tricortical bone grafts and rigid plating is associated with slight subsidence, graft load-sharing, high fusion rate, and excellent clinical outcome. PMID- 17849028 TI - Outpatient anterior cervical discectomy and fusion. AB - The study reported here examined patient safety and satisfaction in 56 patients with cervical radiculopathy secondary to foraminal stenosis or a herniated disc who underwent a total of 58 outpatient anterior cervical discectomy and fusion (ACDF) procedures with iliac crest bone graft or fibular allograft. Patients were discharged 0.8 hour to 6.5 hours (mean, 2.4 hours) after surgery and received 3 home health care visits over 24 hours. Of the 45 satisfaction questionnaires that were completed, 43 (95.6%) indicated patients were satisfied or very satisfied with the surgery, and 35 (77.8%) indicated patients would have the procedure performed on an outpatient basis again. Eleven (19.6%) of the 56 patients did not respond to a satisfaction questionnaire. Outpatient ACDF has high patient satisfaction but does not compromise patient safety. PMID- 17849029 TI - Risk for infection after anterior cervical fusion: prevention with iodophor impregnated incision drapes. AB - Cervical spine infections can have disastrous consequences, but techniques for minimizing infections should be evidence based. In this article, we report the incidence of spine infections in a large cohort of consecutive patients who underwent anterior cervical fusions without iodophor-impregnated incision drapes (3M Ioban; 3M Health Care, St. Paul, Minn) covering the surgical site. We reviewed the records of 581 consecutive patients (294 men, 287 women) who underwent 616 anterior cervical fusions without such drapes over the incision site and who were followed for 1 to 21 years after surgery. Mean age at the time of surgery was 52 years (range, 17-83 years). There was 0% incidence of cervical spinal infections in the group. Need for iodophor-impregnated incision drapes during anterior cervical fusion was not demonstrated. These drapes added unnecessary cost and may decrease skin mobility, making adequate exposure more difficult. PMID- 17849030 TI - Dislocation of the proximal tibiofibular joint in association with a tibial shaft fracture: two case reports and a literature review. AB - Dislocation of the proximal tibiofibular joint (PTFJ) in association with a displaced tibial shaft fracture and an intact fibula is an exceedingly rare injury. We present 2 cases of tibia fractures associated with an intact fibula and a PTFJ dislocation. The first case involves a man who sustained a closed spiral fracture of the distal tibial shaft, with an intact fibula, an anterolaterally dislocated PTFJ, and a partial tear of the lateral collateral ligament. The tibia was percutaneously plated, and the PTFJ was reduced and then stabilized with temporary screw fixation. The second case involves a woman who sustained a closed fracture of the tibia in association with a PTFJ dislocation. The tibia was fixed with an intramedullary nail, and the PTFJ was similarly reduced and fixed with a temporary screw. We also provide a brief literature review focusing on classification of PTFJ dislocations, mechanism of injury, associated injuries, and treatment options. PMID- 17849031 TI - The effect of obesity on quality-of-life improvement after total knee arthroplasty. AB - Obesity has been consistently implicated as a major risk factor in the development and progression of osteoarthritis (OA), and total joint arthroplasty (TJA) has emerged as one of the most efficacious and cost-effective OA treatments. The effectiveness of this treatment manifests itself in both clinical and quality of life (QOL) measures. Given the interrelatedness of obesity and OA, and given the success of TJA in improving QOL, we conducted a study to determine whether obesity would adversely affect QOL improvement in 50 patients who underwent primary total knee arthroplasty for primary knee OA. Our results show that, 6 months after surgery, QOL measures improved more for obese patients than for overweight patients and patients with ideal body weight. PMID- 17849032 TI - Concurrent opening wedge osteotomy and total knee replacement in a patient with posttraumatic arthritis and a varus tibial malunion. PMID- 17849033 TI - Autofusion of the cervical spine in 2 children following open biopsy of Langerhans cell histiocytosis. PMID- 17849035 TI - Mechanisms of thrombophilia. PMID- 17849036 TI - Invasion mechanisms of Gram-positive pathogenic cocci. AB - Gram-positive cocci are important human pathogens. Streptococci and staphylococci in particular are a major threat to human health, since they cause a variety of serious invasive infections. Their invasion into normally sterile sites of the host depends on elaborated bacterial mechanisms that involve adhesion to the host tissue, its degradation, internalisation by host cells, and passage through epithelia and endothelia. Interactions of bacterial surface proteins with proteins of the host's extracellular matrix as well as with cell surface receptors are crucial factors in these processes, and some of the key mechanisms are similar in many pathogenic Gram-positive cocci. Therapies that interfere with these mechanisms may become efficient alternatives to today's antibiotic treatments. PMID- 17849037 TI - The dual role of the contact system in bacterial infectious disease. AB - Hemostasis is a sensitive and tightly regulated process, involving the vascular endothelium and blood cells as well as factors of the coagulation and fibrinolytic cascades. Over the last four decades evidence has accumulated that during infection, inflammatory mediators from the microbe and/or host are capable to modulate the equilibrium between the procoagulant and anticoagulant status of the host. Dependent on the mode of activation, these changes can cause either local or systemic inflammatory reactions that may be beneficial or deleterious to the human host. The present review aims to present the state of the art with respect to the role of the contact system (also known as the intrinsic pathway of coagulation or the kallikrein/kinin system) in innate immunity and systemic inflammatory reactions. PMID- 17849038 TI - Fibrinogen-binding proteins of Gram-positive bacteria. AB - Fibrinogen (Fg), the major clotting protein in blood plasma, plays key roles in blood coagulation and thrombosis. In addition, this 340 kD glycoprotein is a stress inducible protein; its synthesis is dramatically upregulated during inflammation or under exposure to stress such systemic infections. This regulation of Fg expression indicates that Fg also participates in the host defense system against infections. In fact, a number of reported studies have demonstrated the involvement of both the intrinsic and extrinsic pathways of coagulation; the thrombotic and the fibrinolytic systems in the pathophysiology of infectious diseases. It is, therefore, perhaps not surprising that many pathogenic bacteria can interact with Fg and manipulate its biology. This review focuses on the major Fg-binding proteins (Fgbps) from Gram-positive bacteria with an emphasis on those that are known to have an effect on coagulation and thrombosis. PMID- 17849039 TI - Fibrinolysis and host response in bacterial infections. AB - The plasminogen activation system is part of the fibrinolysis which is tightly regulated and protected against dysfunction by various activators and inhibitors. However, microorganisms including bacteria, fungi and also parasites have been proven to interact in a specific manner with components of the fibrinolytic pathways. Pathogenic bacteria are capable to subvert the function of proteases, activators or inhibitors for their own benefits including dissemination within the host and evasion of host inflammatory immune response. Here, we provide a state of the art overview of the divers strategies employed by bacteria to interact with components of the fibrinolytic system and to exploit the system for invasion. Moreover, the role of factors of the fibrinolytic cascade in inflammatory host response due to different bacterial infections will be presented. PMID- 17849040 TI - Effector functions of pathogenic Yersinia species. AB - Pathogenic species of the genus Yersinia suppress and reorient the immune system to infect lymphatic tissues, inner organs and at times also the vasculature. For this purpose yersiniae employ a type III secretion system to translocate effector proteins (Yersinia outer proteins; Yops) into immune cells. Yops often exert unique biochemical activities for modulating the activity of Rho GTP-binding proteins, focal adhesion proteins, inflammatory pathways and cell survival/apoptosis. In this review we will put emphasis on the biochemistry, cell and infection biology of Yersinia effector Yops. PMID- 17849041 TI - Coagulation factor V and thrombophilia: background and mechanisms. AB - Human coagulation factor V (FV) is an essential coagulation protein with functions in both the pro- and anticoagulant pathways. Failure to express and control FV functions can either lead to bleeding, or to thromboembolic disease. Both events may develop into a life-threatening condition. Since the first description of APC resistance, and in particular the description of the so-called factor V(Leiden) mutation, in which a prominent activated protein C cleavage site in FV has been abolished through a mutation in the FV gene, FV has been in the center of attention of thrombosis research. In this review we describe how the functions of FV are expressed and regulated and provide an extensive description of the role that FV plays in the etiology of thromboembolic disease. PMID- 17849042 TI - Molecular basis of protein S deficiency. AB - Protein S deficiency (PSD) has been the most difficult to study among the classical inherited thrombophilic factors. This is in part due to the peculiar biology of protein S (PS), which has an anticoagulant role but no enzymatic activity, and because it interacts with plasma components that function in both haemostasis and inflammation. Clinically, it also has been difficult to define and standardise valuable assays to determine PS status and implication in thrombosis. Despite these drawbacks, at present heterozygous PS deficiency is well established as an autosomal dominant trait associated with an increased risk of thrombosis from data on familial and population studies. Almost two-hundred mutations have been characterised in PROS1, and approximately 30% of them have been characterised in vitro, clarifying the mechanisms leading to PSD. Furthermore, recent studies on the presence of large deletions in PROS1 have increased the number of PSD associated to PROS1 mutations. Finally, the discovery of new functions for PS, both in the anticoagulant system as well as in the interaction with cellular components through receptor tyrosine kinases, is broadening the importance of this molecule in the context of biomedicine. PMID- 17849044 TI - Polymorphisms in the endothelial protein C receptor gene and thrombophilia. AB - The protein C anticoagulant pathway plays a crucial role as a regulator of the blood clotting cascade. Protein C is activated on the vascular endothelial cell membrane by the thrombin-thrombomodulin complex. Once formed, activated protein C (APC) down-regulates thrombin formation by inactivating factors (F)Va and FVIIIa. Endothelial protein C receptor (EPCR) is able to bind protein C and increase the rate of protein C activation. Normal APC generation depends on the precise assemblage, on the surface of endothelial cells, of thrombin, thrombomodulin, protein C and EPCR. Therefore, any change in the efficiency of this assemblage may cause reduced/increased APC generation and modify the risk of thrombosis. This review highlights the different mutations/polymorphisms reported in the EPCR gene and their association with the risk of thrombosis. PMID- 17849043 TI - Factors with conformational effects on haemostatic serpins: implications in thrombosis. AB - Serpins are key actors of systems involving proteolytic reactions, such as the haemostatic system, as they are irreversible suicide inhibitors of serine proteases. The structural flexibility and physical properties of serpins that are required for their efficient inhibitory mechanism also make them especially vulnerable to even minor factors that induce conformational changes in the native form of these molecules, leading to a number of inactive conformations, such as latent, cleaved or polymers. Increasing numbers of conformational mutations affecting haemostatic serpins, mainly antithrombin, the main endogenous anticoagulant, have been described. These mutations cause circulating deficiencies of the molecules, in most cases due to intracellular retention, which may be associated with a hyper-coagulable state. Indeed, conformational mutations in antithrombin have been identified in patients with severe venous thrombosis, which has led to the hypothesis that these disorders might be included in the group of conformational diseases. Moreover, we have recently demonstrated that other factors, including both drugs, such as the treatment with L-asparaginase, or environmental factors, such as high temperatures or hyperlipidemia, may also have conformational consequences on hepatic antithrombin, thus resulting in intracellular aggregation and plasma deficiency, which may increase the risk of thrombosis. In this study, we review the causes of deficiency of haemostatic serpins that may be explained by conformational mechanisms, and their association with an increased risk of venous thrombosis. PMID- 17849045 TI - Current pharmacogenetic developments in oral anticoagulation therapy: the influence of variant VKORC1 and CYP2C9 alleles. AB - For decades coumarins have been the most commonly prescribed drugs for therapy and prophylaxis of thromboembolic conditions. Despite the limitation of their narrow therapeutic dosage window, the broad variation of intra- and inter individual drug requirement, and the relatively high incidence of bleeding complications, prescriptions for coumarins are increasing due to the aging populations in industrialised countries. The identification of the molecular target of coumarins, VKORC1, has greatly improved the understanding of coumarin treatment and illuminated new perspectives for a safer and more individualized oral anticoagulation therapy. Mutations and SNPs within the translated and non translated regions of the VKORC1 gene have been shown to cause coumarin resistance and sensitivity, respectively. Besides the known CYP2C9 variants that affect coumarin metabolism, the haplotype VKORC1*2 representing a frequent SNP within the VKORC1 promoter has been identified as a major determinant of coumarin sensitivity, reducing VKORC1 enzyme activity to 50% of wild type. Homozygous carriers of the VKORC1*2 allele are strongly predisposed to coumarin sensitivity. Using individualized dose adaptation, a significant reduction of bleeding complications can be expected, especially in the initial drug saturation phase. Furthermore, concomitant application of low dose vitamin K may significantly reduce intra-individual coumarin dose variation and, thus, may stabilize oral anticoagulation therapy. The use of new pharmacogenetics-based dosing schemes and the concomitant application of low-dose vitamin K with coumarins will decidedly influence the current practice of oral anticoagulation and greatly improve coumarin drug safety. PMID- 17849046 TI - The role of heparin and allied compounds in the treatment of sepsis. AB - The crosstalk between coagulation and inflammation and the propensity for microthromboembolic disease during sepsis calls for anticoagulant measures to prevent tissue hypoxygenation and to attenuate organ damage and dysfunction. Only one anticoagulant, recombinant human activated protein C (aPC, drotrecogin-alpha) has a proven survival benefit when used as an adjunctive therapy for human sepsis, partly because of its anti-inflammatory effect. However, heparin (-like compounds) may exert similar beneficial anti-inflammatory actions as aPC, in spite of the relatively narrow therapeutic window for anticoagulation. This narrative review is based on a Medline search of relevant basic and clinical studies published in English and discusses the potential role of heparin in modulating inflammatory responses in the treatment of animal models and human sepsis and its harmful sequelae. In any case, the results of a meta-analysis based on animal data suggest a potentially life-saving effect of heparin (-like compounds) in the treatment of sepsis. Therefore, a prospective randomized clinical trial is called upon to study effects in human sepsis. PMID- 17849047 TI - Exclusion of the alpha2 subunit of platelet-activating factor acetylhydrolase 1b (PAFAH1B2) as a prothrombotic gene in a protein C-deficient kindred and population-based case-control sample. AB - Protein C deficiency increases the risk of venous thromboembolic disease among members of Kindred Vermont II, but fails to fully account for the inheritance pattern. A genome scan of the pedigree supported the presence of a prothrombotic gene on chromosome 11q23 (107-119 Mb, nominal P < 0.0001), with weaker support on chromosomes 10p12 (11-25 Mb, P < 0.0003) and 18p11.2-q11 (12-24 Mb, P < 0.0007). The 11q23 region contains the alpha(2) subunit (gene name PAFAH1B2) of platelet activating factor acetylhydrolase 1b, a candidate prothrombotic gene. Re sequencing of the PAFAH1B2 regulatory region in 137 pedigree members, including 25 thrombosis cases, revealed 12 variants; eight were present in only 0-2 affected individuals; the other four assorted into three haplotypes and included three variants predicted to destroy transcription factor-binding sites. More extensive re-sequencing of the PAFAH1B2 gene in 11 affected and five unaffected pedigree members revealed an additional 13 variants that assorted into the same three haplotypes. We rejected as thrombosis risk factors each of the three presumed destructive variants as well as each of the three haplotypes. We also rejected (odds ratio = 1.31 CI: 0.91-1.88) one of the three variants in 469 cases and 472 controls from the Leiden Thrombophilia Study (LETS). Therefore, PAFAH1B2 is not the gene responsible for the linkage evidence on chromosome 11q23. PMID- 17849048 TI - Molecular characterization of four ADAMTS13 mutations responsible for congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome). AB - ADAMTS13 mutations S203P, R268P, R507Q and A596V were previously identified in French patients with hereditary thrombotic thrombocytopenic purpura (TTP) (Upshaw Schulman syndrome). Mutated recombinant (r) ADAMTS13 were transiently expressed in COS-7 cells and characterized in comparison with wild-type (WT) rADAMTS13. ADAMTS13 antigen was qualitatively and quantitatively estimated by electrophoretic analysis and ELISA. Enzymatic activity was qualitatively and quantitatively estimated using GST-VWF73, FRETS-VWF73 fragments and full-length rVWF-WT as substrates. The four mutants and rADAMTS13-WT were present within the cells. Secretion level of rADAMTS13-WT reached 1,200 ng/ml. The four mutations strongly altered the secretion and biological activity of rADAMTS13. The percentage secretion was 21, 38 and 17% for rADAMTS13-S203P, -R268P and -A596V compared with rADAMTS13-WT. rADAMTS13-R507Q concentration was under the detection limit of the assay. In the four cases, no enzymatic activity was detected. After concentration, we confirmed that mutations S203P and R268P totally abolished the proteolytic activity of ADAMTS13. Due to the very low protease concentration, activity of rADAMTS13-R507Q was below the threshold of the assays. rADAMTS13 A596V had no proteolytic activity towards the full-length rVWF-WT whereas it exhibited a decreased specific activity of about 30% of that of rADAMTS13-WT towards FRETS-VWF73 fragment. Binding study of mutated rADAMTS13-S203P, -R268P and -A596V showed that the three mutations strongly decreased the interaction of ADAMTS13 with VWF. In conclusion, the four mutations, which led to a secretion defect, a loss of enzymatic activity and a decreased binding to the substrate, are responsible for the hereditary TTP in patients. PMID- 17849049 TI - Thrombin generation in plasma of healthy adults and children: chromogenic versus fluorogenic thrombogram analysis. AB - Coagulation tests and coagulation factor assays have been complemented recently with experimental tests to measure the total amount of thrombin formed. We have presently analyzed thrombin generation of healthy adult and paediatric plasma samples via a fluorogenic and a chromogenic method. The chromogenic method was performed on the fully automated Behring Coagulation System (BCS) and fluorogenic assays via Calibrated Automated Thrombography (CAT), after coagulation induction by various tissue factor (TF) concentrations. Sample distribution and variability were analyzed for the four main coagulation parameters, derived via computerized curve analysis in each method. Results for both methods were correlated. At the recommended TF concentration (300 pM), thrombin generation via BCS was less variable than via CAT (1-6 pM), but at comparable TF concentrations (1-6 pM), the CAT sensitivity was higher than that of BCS. Inhibition of intrinsic coagulation with the anti-factor VIII antibody BO2C11 revealed that the BCS detected extrinsic coagulation exclusively, at all TF concentrations tested. In contrast, at low TF concentrations (1 and 2.5 pM), via CAT, intrinsic coagulation pathway amplification was measured. At standardized TF concentrations (300 pM in BCS vs. 2.5 pM in CAT), different reference values between adults and children were found, for all parameters, except Tmax. In adult samples, the best correlation between both methods was observed for ETP(CAT) versus ETP(BCS) and for Peak height(CAT) versus Cmax(BCS), when thrombin generation was exclusively extrinsic (300 pM in BCS vs. 6 pM in CAT). In conclusion, differential thrombin generation characteristics in BCS and CAT are relevant for their clinical applicability. PMID- 17849050 TI - Heme oxygenase-1 inducer hemin prevents vascular thrombosis. AB - Hemin is a heme oxygenase-1 (HO-1) inducer which provides endogenous carbon monoxide known for playing roles in cell proliferation, inflammation or aggregation process. The objective of the current study was to examine the effect of prophylactic treatment with hemin in a thrombosis vascular model. Three groups of Wistar rats, control (n = 6), hemin (n = 6) and hemin + HO-1 inhibitor (n = 6), were used for this study. Hemin-treated animals received hemin (50 mg/kg/d; I.P.) for seven days and HO-1 inhibitor group received hemin at the same dose and SnPP IX (60 mg/kg/d; I.P.). All animals were exposed to electric stimulation of the left carotid according to Kawasaki's procedure to induce reproducible thrombus formation. The hemin treatment did not induce blood pressure disturbance. Effects of hemin on vascular thrombosis were quantified by histopathology and its influence on haemostasis was assessed by measuring prothrombin time (PT), activated partial thromboplastin time (APTT) and blood parameters at the end of treatment. The HO-1 mRNA and protein level variation were also checked out. Results showed that chronic treatment with hemin significantly (p < 0.01) reduced the vascular occlusion degree when compared to control and hemin SnPP groups with 7.2 +/- 4.6 vs. 71.1 +/- 14.7 and 74.0 +/- 8.8%, respectively. Moreover, we observed significant (p < 0.05) perturbations of blood parameters in hemin-treated and hemin-SnPP treated rats. Interestingly, hemin treatment did not significantly increase both PT and APTT. Finally, the HO 1 mRNA and protein levels were increased in hemin-treated carotid artery. In conclusion, hemin by inducing HO-1 expression may be a preventive agent against clinical disorders associated to an increased risk of thrombosis events and may limit haemorrhagic risks. PMID- 17849051 TI - Influence of lipids and obesity on haemorheological parameters in patients with deep vein thrombosis. AB - It is not well established whether haemorheological alterations constitute independent risk factors for deep vein thrombosis (DVT). We have determined in 149 DVT patients and in 185 control subjects the body mass index (BMI), the haemorheological profile: blood viscosity (BV), plasma viscosity (PV), fibrinogen (Fg), erythrocyte aggregation (EA), erythrocyte deformability (ED) and plasma lipids. In the crude analysis BMI, Fg, PV, EA, triglycerides (TG) and ApoB were statistically higher and HDL cholesterol (HDL-Chol) statistically lower in DVT patients than in controls. No differences in BV and ED were observed. After BMI adjustment, Fg, PV and EA remained statistically higher in DVT cases than in controls (P = 0.013; P = 0.012; P = 0.013; P = 0.028, respectively). When the risk of DVT associated with these variables (using cut-offs that corresponded to the mean plus one SD of the control group) was estimated, EA > 8.2 and PV > 1.28 mPa . s were significantly associated with DVT even further adjustment for lipids and obesity (OR = 2.78, P = 0.004; OR = 1.91, P = 0.024, respectively). However, PV did not remain statistically significant after additional adjustment for Fg. When we consider together all the analyzed variables in order to control every variable for each other, TG > 175 mg/dl (OR = 3,2, P = 0.004) and BMI > 30 kg/m(2) (OR = 3.5, P = 0.003), were also independently associated with a greater risk of DVT. Our results suggest that increased EA constitute an independent risk factor for DVT. However, when associated to hyperlipidaemia and obesity it further increases thrombotic risk. PMID- 17849052 TI - Thrombomodulin-mediated catabolism of protein C by pleural mesothelial and vascular endothelial cells. AB - Pleural mesothelial and vascular endothelial cells express protein C (PC) pathway components including thrombomodulin (TM) and endothelial protein C receptor (EPCR) and activate PC by the thrombin-TM dependent mechanism. We used these cells as model systems to identify molecules involved in endocytosis and degradation of PC. We find that mesothelial and endothelial cells can bind, internalize and degrade PC. Addition of thrombin markedly induced degradation of PC by these cells in a TM-dependent fashion, implicating the involvement of the thrombin-TM complex in internalization and degradation of PC. This observation defines a novel function for the thrombin-TM complex as a degradation receptor for PC and suggests that PC is degraded concurrent with its activation. A PC Gla domain mutant, which is unable to bind to the EPCR, was degraded by the cells to a lesser extent than wild-type PC, implicating the PC degradation concurrent with its activation. Consistent with the role of thrombin-TM complex as a degradation receptor, the catalytically inactive thrombin-S195A also induced PC degradation though to a lesser extent than wild-type thrombin. This suggests that generation of activated PC (APC) can contribute to accumulation of degradation products, but is not essential for the thrombin-induced degradation of PC. The thrombin-TM mediated degradation of PC by both cell types suggest a previously unrecognized mechanism, which can contribute to PC consumption. This mechanism may be pathophysiologically relevant and can contribute to an acquired PC deficiency in conditions characterized by sustained thrombin generation. PMID- 17849053 TI - Impaired endothelial antithrombotic activity following short-term interruption of continuous subcutaneous insulin infusion in type 1 diabetic patients. AB - Review of literature has shown an increased rate of thrombotic complications in diabetic patients with frequent episodes of hyperketonemia. However, the mechanisms by which ketosis promotes vascular disease in diabetic patients are unclear. It was the aim of this study to investigate early changes in haemostatic parameters and oxidative stress markers during the hyperketonemic status which follows the interruption of continuous subcutaneous insulin infusion (CSII) in type I diabetic patients. Eight CSII-treated type I diabetic patients underwent a 4-hour pump arrest. Blood glucose, insulin and 3-hydroxybutirate were measured to verify the metabolic response. A vein-occlusive (VO) test was performed for the determination of tPA and PAI-1 activities and their antigen levels before and after the CSII arrest. Coagulation factor VII and VIII were evaluated by one stage PT and PTT method, respectively. TF, vWF, tPA and PAI-1 antigens were determined by ELISA, whereas tPA and PAI-1 activities using chromogenic methods. Plasma malondialdehyde (MDA) and protein carbonyl groups (PCG) levels were determined by HPLC and spectrophotometry, respectively. After the insulin deprivation phase, post-VO tPA antigen level significantly decreased (P = 0.0391), whereas TF and post-VO PAI-1 activity and antigen levels significantly increased (P = 0.0156 and P = 0.0234, respectively). Plasma MDA and PCG levels were 1.88-fold and 1.74-fold higher than baseline values, respectively. In conclusion, the impairment of the fibrinolytic potential and the increases in TF, MDA and PCG levels may enhance the risk of both arterial and venous thrombosis during ketosis. Thus, early detection of hyperketonemia in DM patients could contribute to the prevention of life-threatening vascular events. PMID- 17849054 TI - Effects of toll-like receptor-4 gene polymorphisms on soluble P-selectin and von Willebrand factor levels in hypercholesterolemic patients. AB - Toll-like receptor-4 (TLR-4) gene polymorphisms have been associated with a lower risk of atherosclerosis. High levels of soluble P-selectin (sP-selectin) and von Willebrand factor predict an increased risk for cardiovascular events and correlate to atherosclerotic risk factors. The relationship between these markers and TLR-4 gene polymorphisms was evaluated in a cohort of consecutive hypercholesterolemic outpatients. TLR-4 gene polymorphisms were detected in 48 out of 330 (14%) patients with hypercholesterolemia. Lipid and inflammatory markers, sP-selectin and von Willebrand were evaluated in carriers and in 96 (ratio 2:1 to cases) age- and sex-matched TLR-4 wild-type patients randomly selected from the same population. A cohort of normocholesterolemic outpatients (n = 262) served as the control group. sP-selectin was sensibly lower in carriers of TLR-4 variants as compared to wild-types and controls (89 ng/ml vs. 162 ng/ml and 163 ng/dl, respectively, p = 0.0001). Similarly, carriers showed lower von Willebrand factor values (683 mU/ml) than wild-types (910 mU/ml; p = 0.001). In multivariate analysis, TLR-4 gene polymorphisms were positively associated with sP-selectin, whereas the relationship with von Willebrand factor was no longer significant. HMG-CoA reductase inhibitors reduced sP-selectin and von Willebrand factor levels independently of TLR-4 gene variants. Plasma concentrations of these markers, however, remained lower in carriers of TLR-4 gene polymorphisms even after cholesterol lowering. In conclusion, carriership of Asp299 and Thr399Ile TLR-4 gene polymorphisms is associated with lower levels of sP-selectin and von Willebrand factor among hypercholesterolemic patients. While the underlying mechanisms remain to be investigated, such an association may indicate a protective effect of TLR-4 variants for atherosclerosis. PMID- 17849056 TI - Venous thromboembolism in patients with active cancer. AB - Patients with cancer have an increased risk of venous thromboembolism (VTE). To further define the demographics, comorbidities, and risk factors of VTE in these patients, we analyzed a prospective registry of 5,451 patients with ultrasound confirmed deep vein thrombosis (DVT) from 183 hospitals in the United States. Cancer was reported in 1,768 (39%), of whom 1,096 (62.0%) had active cancer. Of these, 599 (54.7%) were receiving chemotherapy, and 226 (20.6%) had metastases. Lung (18.5%), colorectal (11.8%), and breast cancer (9.0%) were among the most common cancer types. Cancer patients were younger (median age 66 years vs. 70 years; p < 0.0001), were more likely to be male (50.4% vs. 44.5%; p = 0.0005), and had a lower average body mass index (26.6 kg/m(2) vs. 28.9 kg/m(2); p < 0.0001). Cancer patients less often received VTE prophylaxis prior to development of DVT compared to those with no cancer (308 of 1,096, 28.2% vs. 1,196 of 3,444, 34.6%; p < 0.0001). For DVT therapy, low-molecular-weight heparin (LMWH) as monotherapy without warfarin (142 of 1,086, 13.1% vs. 300 of 3,429, 8.7%; p < 0.0001) and inferior vena caval filters (234 of 1,086, 21.5% vs. 473 of 3,429, 13.8%; p < 0.0001) were utilized more often in cancer patients than in DVT patients without cancer. Cancer patients with DVT and neurological disease were twice as likely to receive inferior vena caval filters than those with no cancer (odds ratio 2.17, p = 0.005). In conclusion, cancer patients who develop DVT receive prophylaxis less often and more often receive filters than patients with no cancer who develop DVT. Future studies should focus on ways to improve implementation of prophylaxis in cancer patients and to further define the indications, efficacy, and safety of inferior vena caval filters in this population. PMID- 17849055 TI - Cardiovascular risk factors and global risk of fatal cardiovascular disease are positively correlated between partners of 802 married couples from different European countries. Report from the IMMIDIET project. AB - Shared environmental factors may confer to spouses a similar risk for cardiovascular disease. We aimed at investigating in pairs the concordance in risk factors for cardiovascular disease and in global risk of cardiovascular events. In the framework of the IMMIDIET Project, married couples, recruited randomly from general practice, were studied. One thousand six hundred and four apparently healthy subjects aged 25-74 years from three different European populations were enrolled. Individual cardiovascular risks were estimated using SCORE risk equations. Age was strongly correlated within couples (r = 0.86, P < 0.0001). In multivariate model, within-pair correlation was high for social status (r = 0.49; percentage of explained variation = 24%) and percent of calories from lipids (r = 0.34; 12%). Concerning conventional metabolic risk factors, percentage of explained variation varied from 0.5% (triglycerides) to 11% (glucose). Among new risk factors, activated factor VII showed the strongest correlation (r = 0.28) and C-reactive protein the lowest (r = 0.13). Either total, coronary or non-coronary risk estimates at 10 years were strongly correlated within pairs: the risk of a member explained about two thirds of the cardiovascular risk of the partner. Spouse pairs share common lifestyle habits, common and new metabolic risk factors and the predicted global risk of cardiovascular events. If the individual risk of a person is influenced by the risk of his/her partner, decreasing the risk in a member of the pair should also decrease the risk in the partner. These concepts may have important public health consequences in targeting screening or disease prevention measures towards partners of people with cardiovascular risk. PMID- 17849058 TI - Factor V Leiden and the etiology of inflammatory bowel disease. AB - Inflammatory bowel disease (IBD) refers to two chronic diseases that cause inflammation of the intestines: ulcerative colitis and Crohn's disease. Patients suffering from IBD have a three-fold increased risk of venous thrombosis compared with matched controls. Importantly, thromboembolic disease is a significant cause of morbidity and mortality in patients with IBD. However, despite several supporting observations it is still elusive whether activation of the blood coagulation cascade is involved in the etiology and pathogenesis of IBD. To confirm or refute the hypothesis that activated blood coagulation aggravates the development of IBD, we subjected wildtype and homozygous FV Leiden mice to a model of DSS-induced colitis. Experimental colitis led to a reduction in body weight, shortening of the colon and increased colon weight. In addition, DSS treatment led to ulcerations, edema formation, crypt loss, fibrosis and the influx of inflammatory cells into the colon. However, the FV Leiden genotype had no significant effect on any of the DSS-induced symptoms of colitis. We therefore conclude that the FV Leiden allele has no effect in murine colitis and we thus question the importance of activated blood coagulation in the etiology or pathogenesis of IBD. PMID- 17849057 TI - A thromboxane A2/prostaglandin H2 receptor antagonist (S18886) shows high antithrombotic efficacy in an experimental model of stent-induced thrombosis. AB - Acute thrombosis is a threat in patients undergoing percutaneous coronary intervention with stent implantation. Our objective was to determine if stent induced thrombus formation could be inhibited by oral treatment with a thromboxane A(2)/prostaglandin H(2) receptor antagonist (TPr; S18886) as an alternative to standard therapy. Pigs were allocated in the following treatment (p.o) groups: I) clopidogrel (CLOP); II) ASA; III) S18886; IV) ASA+CLOP; and V) placebo-control. Damaged vessel was placed in the Badimon chamber containing a stent and perfused at 212/s. Antithrombotic effects were assessed as (111)In platelet deposition (PD) in two series (60 and 180 min after drug intake). Fibrin(ogen) deposition, light transmittance aggregometry (LTA; collagen, U46619, and ADP), and bleeding time (BT) were also evaluated. After 60 min S18886 reduced PD < or =48%, 40%, and 35% vs placebo, CLOP-, and ASA-treated animals, respectively (P < 0.05), while ASA+CLOP showed a 58% reduction versus placebo (P < 0.01). After 3 hours, ASA+CLOP decreased PD by 55%, S18886 by 40%, CLOP alone by 28% (P < 0.05), and ASA showed no inhibition versus placebo. Similar effects were found in S18886- and ASA+CLOP-treated animals at both times. Fibrin(ogen) deposition followed the same pattern. Collagen-induced LTA was significantly reduced by ASA, ASA+CLOP, and S18886; S18886 abolished U46619-induced LTA; and, CLOP +/- ASA reduced ADP-induced LTA in a time-dependent manner. TPr blockade did not prolong BT, whereas CLOP +/- ASA significantly did (P < 0.0001). In conclusion, blockade of the TPr provided a fast and potent platelet inhibitory effect in a porcine model of in-stent thrombosis comparable to that of blocking both the ADP receptor and cyclooxygenase activation; in addition, TPr provided a more favorable bleeding risk profile. PMID- 17849059 TI - Local paclitaxel delivery after coronary stenting in an experimental animal model. AB - The goal of this study was to test the safety and efficacy of local paclitaxel delivery via a newly designed application catheter in an experimental animal study. Drug-eluting stents reduce restenosis in comparison to bare-metal stents. The drug-eluting polymer, however, may exert potential thrombogenic and inflammatory effects. A catheter-based local paclitaxel delivery offers further advantages, particularly a homogenous drug transfer into the vessel wall and a pharmacotherapy of the stent edges. In 30 pigs, both bare-metal stent (3.0 x 13 mm) implantation and balloon angioplasty were performed. Ten pigs received subsequent local delivery of paclitaxel-solution via a newly designed catheter (Genie, ACROSTAK corp., Switzerland), 10 animals served as a sham group and received vehicle (0.9% NaCl solution) and 10 animals were used as a control group. All animals were treated with aspirin and clopidogrel to prevent stent thrombosis. After final angiography the vessels were excised 42 days after intervention and prepared for histological and histomorphometric analysis. All coronary arteries showed complete endothelialization 42 days following treatment. Paclitaxel treatment led to a marked reduction of neointimal proliferation either post stent implantation (neointimal area: 1.04 +/- 0.10 mm(2) vs. 2.37 +/- 0.23 mm(2), p < 0.001) or post balloon dilatation (neontimal area: 0.35 +/- 0.14 mm(2), vs. 0.68 +/- 0.24 mm(2), p < 0.01). There were no significant angiographic or histomorphometric differences between the control and the sham group. In both paclitaxel groups neither angiographic edge phenomena nor a significant histomorphometric inflammatory response were found in the treated vessel segments. In conclusion, the local application of paclitaxel via the Genie catheter is safe and effective to significantly reduce the proliferative response post-stent implantation or balloon dilatation in an experimental animal model. PMID- 17849060 TI - JAK2V617F mutation as a marker of a latent myeloproliferative disorder in a patient with Budd-Chiari syndrome and factor V Leiden mutation. PMID- 17849061 TI - Factor V C1149G and 5609-10INSCGTGGTT causing factor V deficiency: molecular characterization by in-vitro expression. PMID- 17849062 TI - Acquired factor V inhibitor after haematopoietic stem cell transplantation. PMID- 17849063 TI - Severe factor VII deficiency caused by a novel point mutation (Arg353Pro) combined with a rare Cys22Arg mutation. PMID- 17849064 TI - Clinical and biological features of 3 cases of hypofibrinogenemia associated with three different mutations (gamma Ala341Thr, Bbeta Tyr326Cys and Aalpha Asp496Asn). PMID- 17849065 TI - Protein C deficiency screening using a thrombin generation assay - an upgrade. PMID- 17849066 TI - Activated protein C resistance test using factor VIII-deficient plasma: a new approach to the venous thrombotic risk? PMID- 17849067 TI - Report of a novel kindred with antithrombin heparin-binding site variant (47 Arg to His): demand for an automated progressive antithrombin assay to detect molecular variants with low thrombotic risk. PMID- 17849068 TI - Acute aldosterone infusion enhances thrombosis development in normotensive rats. PMID- 17849069 TI - Stroke in paroxysmal nocturnal haemoglobinuria: patterns of disease and outcome. PMID- 17849070 TI - Haemostatic proteins gene polymorphisms in patients with unusual vein thrombosis and Ph-myeloproliferative disorders. PMID- 17849071 TI - Anomalous left coronary artery from the right sinus of valsalva and noncompaction of the left ventricle. AB - Anomalous origin of the left coronary artery is a well-known cause of sudden death. Noncompaction of the ventricular myocardium is a cardiomyopathy characterized by prominent trabeculae and deep intertrabecular recesses. Both anomalies are rare. We report the case of a child with both anomalous origin of the left coronary artery from the right sinus of Valsalva and noncompaction of the left ventricular myocardium found during an evaluation for Kawasaki's disease. PMID- 17849072 TI - Left ventricular cardiac fibroma in a child presenting with ventricular tachycardia. AB - Cardiac tumors in children are rare. Although most are histologically benign, they can be associated with life-threatening arrhythmias and sudden death. We report a 7-year-old boy, with a first episode of symptomatic tachycardia, who was found to have a left ventricular (LV) fibroma. He had a normal echocardiogram prior to an electrophysiology study, which revealed a sustained monomorphic ventricular tachycardia and a radio-opacity near the LV apex. These findings prompted a cardiac MRI, which demonstrated a discrete mass on his LV apex and free wall. Our case emphasizes that structural heart disease should be aggressively pursued in children presenting with ventricular tachycardia. PMID- 17849073 TI - Torsades de Pointes ventricular tachycardia in a pediatric patient treated with fluconazole. AB - Fluconazole is an antifungal medication that has been reported to cause prolongation of the QT interval and Torsades de Pointes (TdP) ventricular tachycardia in adults. We describe the case of an 11-year-old child treated with fluconazole who developed ventricular arrhythmia culminating in TdP. We discuss the possible roles played by genetic and environmental factors in this child's rhythm disturbances. After briefly summarizing similar cases from the adult literature, we outline the putative mechanism by which fluconazole may cause arrhythmia. This case should alert pediatricians to the possible risks of fluconazole use, especially in the presence of electrolyte abnormalities, diuretic use, therapy with other pro-arrhythmic agents, or suspicion of congenital Long-QT Syndrome. PMID- 17849074 TI - CT artifact mimicking pulmonary embolism in a patient with single ventricle. PMID- 17849075 TI - Anomalous origin of a coronary artery from the opposite sinus of Valsalva with an interarterial course: clinical profile and approach to management in the pediatric population. AB - An anomalous origin of a coronary artery from the opposite sinus of Valsalva with an interarterial course (interarterial coronary artery [IACA]) is a rare congenital anomaly associated with sudden cardiac death. The cardiac and surgical databases at a single pediatric institution were reviewed for a description of the clinical profiles and associated risk factors of this coronary anomaly. From 1994 to 2006, IACA was diagnosed for 31 patients with a median age of 6.2 years (range, birth to 16 years). The symptoms for 6 (19%) of the 10 patients (32%) presenting with symptoms were deemed to be cardiac in origin. The symptoms for the remaining 21 patients (68%) were incidental findings. Of the 31 patients, 29 (94%) had normal resting electrocardiograms (ECG). A total of 17 patients underwent dobutamine stress echo. None had wall motion abnormalities, but two had ECG changes indicating ischemia, and 4 had abnormal coronary flow, as detected by Doppler echocardiography. Seven patients, with either acute symptoms or testing suggestive of ischemia, underwent surgery. All seven had an interarterial left main coronary artery. There was one cardiac-related death. No sudden death was found in either the surgery or nonsurgery group during the mean follow-up period of 23 and 58 months, respectively. Whether surgical intervention modifies the natural history of the anomaly or not remains to be determined. PMID- 17849077 TI - Differences in cortisol response affect the distinction of observed reactive and proactive aggression in children with aggressive behaviour disorders. AB - Various researchers distinguished two categories of aggressive behaviour, namely reactive and proactive aggression. Reactive aggression is an aggressive response to a perceived threat or provocation, whereas proactive aggression is behaviour that anticipates a reward. In the present study, including both a sample of disruptive behaviour disordered (DBD) and normal control (NC) children, we observed reactive and proactive aggressive behaviour during an experimental dyadic play session. DBD children showed more observed reactive and proactive aggression. Subsequently, we investigated whether the observed measures correlated with parent-rated measures of reactive and proactive aggression in. We distinguished in both NC and DBD children a subgroup showing a rise in cortisol level, i.e. responders, and a subgroup who did not show a rise in cortisol, i.e. non-responders. Results suggest that differences in the cortisol response affects the correspondence between observed and parent-rated reactive and proactive aggression since only DBD non-responders showed the expected correlations. PMID- 17849076 TI - The efficacy of mitral valve surgery in children with dilated cardiomyopathy and severe mitral regurgitation. AB - Severe mitral regurgitation predicts poor outcomes in adults with left ventricular dysfunction. Frequently, adult patients now undergo initial mitral valve surgery instead of heart transplant. Pediatric data are limited. This study evaluates the efficacy of mitral valve surgery for severe mitral regurgitation in children with dilated cardiomyopathy. This is a single-institution experience in seven children (range, 0.5-10.9 years) with severe mitral regurgitation and dilated cardiomyopathy who underwent mitral valve surgery between January 1988 and February 2005, with follow-up to January 2006. Children with dilated cardiomyopathy had a depressed fractional shortening preoperatively (24.4% +/- 6.1%) that remained depressed (22.9% +/- 7.6%) 1.3 +/- 1.2 years after surgery (p = 0.50). Left ventricular end-diastolic (6.5 +/- 1.5 to 4.8 +/- 1.8 z-scores, p < 0.01) and end-systolic (6.8 +/- 1.5 to 5.5 +/- 2.1 z-scores, p < 0.05) dimensions improved. Hospitalization frequency had a median decrease of 6.0 hospitalizations per year (p < 0.02). Three patients were transplanted 0.2, 2.4, and 3.5 years after surgery. There was no perioperative mortality. Mitral valve surgery in children with dilated cardiomyopathy was performed safely and improved symptoms, stabilizing ventricular dysfunction in most patients. Mitral valve surgery should be considered prior to heart transplant in children with dilated cardiomyopathy and severe mitral regurgitation. PMID- 17849078 TI - Joint attention development in toddlers with autism. AB - Deficits in Joint Attention (JA) may be one of the earliest signs of Autism Spectrum Disorders (ASD). In this longitudinal study we investigated several types of JA behaviors at the age of 24 and 42 months, and their development over time. Eleven children with ASD, 10 children with other developmental disorders, and eight children without a developmental disorder participated. It was found that children with ASD showed significantly less JA at the age of 24 months. At this age, the various types of JA (Basic Joint Attention, Associated Joint Attention, Joint Visual Attention) were correlated with developmental level and number of autistic characteristics. However, at the age of 42 months, these associations were absent. Although children with ASD may show less JA at the age of 24 months compared to other groups of children, by the age of 42 months they reach about the same level of JA, except for joint visual attention. In fact, at both ages, children with ASD differed consistently only on JVA from the other groups. JVA may be a core component of an early screening device for ASD. PMID- 17849079 TI - Patients with eating disorders and their siblings. An investigation of body image perceptions. AB - Little is known about body images of siblings of patients with eating disorders. In this study we investigated body images of patients with anorexia or bulimia nervosa and of the patients' brothers and sisters. A computer program was employed that allows modeling perceived and desired body images of patients and family members. Patients, siblings and male and female control subjects rated their body images. The selected images were compared with anthropometric data. All subjects also filled out a body image questionnaire. Data from 30 patients, 38 siblings, and 60 control subjects are presented. Siblings did not differ from healthy control subjects. Self-ideal discrepancy was different in patients with anorexia and their sisters. Body image was more negative in patients than in their sisters. Siblings of patients with eating disorders seem to be rather unimpaired in terms of body image disturbances. PMID- 17849080 TI - Is social anxiety disorder in childhood associated with developmental deficit/delay? AB - Children with social anxiety disorder (SAD) have been reported to display reduced social skills. Less attention has been paid to whether neurodevelopmental deficits/delays (NDD's) in language and motor function may contribute to their impaired social skills. The present study aimed to assess the extent of language and motor impairment in children with SAD. A population-based screened sample consisting of 150 children (11-12 years) was assessed with a diagnostic interview (Kiddie-SADS), the Wechsler Abbreviated Scale of Intelligence (WASI) and the Motor Assessment Battery for Children (MABC). Test results were compared across five diagnostic groups: SAD (n=29); ADHD (n=23); SAD and ADHD (n=6); "other disorder" (n=44) and "no disorder" (n=48). Delays in language and motor development as reported by mother were also investigated. Verbal IQ and motor skills were reduced and maternally reported delay was more frequent in the SAD group compared to the "other disorder" and "no disorder" group. PMID- 17849081 TI - Subtypes of learning disabilities: neuropsychological and behavioural functioning of 495 children referred for multidisciplinary assessment. AB - Aim of the present study was two fold: (1) to evaluate the course of referring and diagnosing Learning Disabilities (LD) and the contribution of multidisciplinary assessment and (2) to describe characteristics of three LD subtypes: Attention with or without Motor function Disabilities (AMD), Verbal Learning Disabilities (VLD) and Non-Verbal Learning Disabilities (NVLD). Diagnostics, behavioural and neuropsychological data from 495 children aged 6-17 years were described. First, AMD and VLD was the most frequent LD. Multidisciplinary assessment could contribute to the diagnostic process of LD, especially in diagnosing uncommon LD and comorbidities. Secondly, behavioural ratings, information processing, attention regularity and visual-motor integration proved to be most sensitive in discriminating between the three LD subtypes. However, diagnosing NVLD requires additional developmental information. Multiple discriminant function analysis correctly classified 61.7% of a selection of the present sample into LD subtypes as diagnosed by the multidisciplinary team. It is believed that the three subtypes are clinically relevant and suggestions are made to test the present classification functions in an independent sample, preferably diagnosed using a structured diagnostic interview. PMID- 17849082 TI - The effect of temperature on enzyme activity: new insights and their implications. AB - The two established thermal properties of enzymes are their activation energy and their thermal stability. Arising from careful measurements of the thermal behaviour of enzymes, a new model, the Equilibrium Model, has been developed to explain more fully the effects of temperature on enzymes. The model describes the effect of temperature on enzyme activity in terms of a rapidly reversible active inactive transition, in addition to an irreversible thermal inactivation. Two new thermal parameters, Teq and Delta Heq, describe the active-inactive transition, and enable a complete description of the effect of temperature on enzyme activity. We review here the Model itself, methods for the determination of Teq and Delta Heq, and the implications of the Model for the environmental adaptation and evolution of enzymes, and for biotechnology. PMID- 17849083 TI - The family of iron responsive RNA structures regulated by changes in cellular iron and oxygen. AB - The life of aerobes is dependent on iron and oxygen for efficient bioenergetics. Due to potential risks associated with iron/oxygen chemistry, iron acquisition, concentration, storage, utilization, and efflux are tightly regulated in the cell. A central role in regulating iron/oxygen chemistry in animals is played by mRNA translation or turnover via the iron responsive element (IRE)/iron regulatory protein (IRP) system. The IRE family is composed of three-dimensional RNA structures located in 3' or 5' untranslated regions of mRNA. To date, there are 11 different IRE mRNAs in the family, regulated through translation initiation or mRNA stability. Iron or oxidant stimuli induce a set of graded responses related to mRNA-specific IRE substructures, indicated by differential responses to iron in vivo and binding IRPs in vitro. Molecular effects of phosphorylation, iron and oxygen remain to be added to the structural information of the IRE-RNA and IRP repressor in the regulatory complex. PMID- 17849084 TI - Treatment and prognosis of brain metastases from breast cancer. AB - BACKGROUND: To analyze retrospectively the results of treatments for patients with brain metastases from breast cancer. MATERIALS AND METHODS: The records of 65 breast cancer patients with brain metastases who were treated between 1985 and 2005 were reviewed. For brain metastases, 11 patients (17%) were treated with surgical resection followed by radiotherapy, and the remaining 54 patients were treated with radiotherapy alone. Systemic chemotherapy was also administered to 11 patients after brain radiotherapy. RESULTS: The overall median survival for all patients was 6.1 months (range, 0.4-82.2 months). In univariate analysis, treatment modality, Karnofsky performance status (KPS), administration of systemic chemotherapy, extracranial disease status and total radiation dose each had significant impact on overall survival, and in multivariate analysis, treatment modality, KPS and administration of systemic chemotherapy were significant prognostic factors. Eight patients survived for more than 2 years after the diagnosis of brain metastases, and all these patients were treated with surgical resection and/or systemic chemotherapy in addition to radiotherapy. For the 45 patients treated with palliative radiotherapy (without systemic chemotherapy), the improvements in neurological symptoms were observed in 35 patients (78%), with the median duration of improvement of 3.1 months (range, 1.5 4.4 months). CONCLUSIONS: The prognoses for patients with brain metastases from breast cancer were generally poor, although selected patients may survive longer with intensive brain tumor treatment, such as surgical resection and/or systemic chemotherapy in addition to brain radiotherapy. For patients with unfavorable prognoses, palliative radiotherapy was effective in improving the quality of the remaining lifetime. PMID- 17849085 TI - Aptameric enzyme subunit for homogeneous DNA sensing. AB - We have developed an aptameric enzyme subunit (AES) which can detect the DNA in a homogeneous solution. The AES is an artificial enzyme subunit composed of an enzyme-inhibiting aptamer bearing a target-molecule binding site. We connected a probe DNA to a thrombin-inhibiting aptamer at its 5' or 3' end. The inhibitory activity of the thrombin-inhibiting aptamer bearing the probe DNA decreased compared to that of the original aptamer; however, it recovered upon hybridization with the target DNA. Using this AES, we were able to detect target DNAs by measuring the thrombin activity in a homogeneous solution. PMID- 17849086 TI - Hydrogen production in anaerobic and microaerobic Thermotoga neapolitana. AB - We have tested the hypothesis (Van Ooteghem et al. Appl Biochem Biotechnol 2002 98-100: 177-189) that microaerobic metabolism may increase the yield of H(2) from the thermophilic bacterium Thermotoga neapolitana. In anaerobic conditions, T. neapolitana converted glucose into acetic acid and lactic acid and yielded 2.4 +/ 0.3 mol H(2) mol(-1) glucose. The bacterium tolerated low O(2) partial pressures but the H(2) yield was not improved under microaerobic conditions. Our results indicate that T. neapolitana only produces H(2) by anaerobic metabolism, and that the yield of H(2) can be maximised by minimising the production of lactic acid. PMID- 17849087 TI - Chromium-reducing and plant growth-promoting Mesorhizobium improves chickpea growth in chromium-amended soil. AB - Mesorhizobium strain RC3, isolated from chickpea nodules, tolerated chromium up to 500 mug/ml and reduced it by 90% at pH 7 after 120 h. It produced plant growth promoting substances, both in the presence and absence of chromium. Strain RC3 produced 35 mug indole acetic acid/ml in Luria Bertani broth with 100 mg tryptophan/ml, which decreased with an increase in chromium concentration. Chromium application to soil at 136 mg/kg was toxic to chickpea plants but when RC3 at 136 mg/kg was also added, it increased the dry matter accumulation, number of nodules, seed yield and grain protein by 71, 86, 36 and 16%, respectively, compared to non-inoculated plants. Nitrogen in roots and shoots were increased by 46 and 40%, respectively, at 136 mg Cr/kg. The bio-inoculant decreased the uptake of chromium by 14, 34 and 29% in roots, shoots and grains, respectively. PMID- 17849088 TI - Heterologous expression of cholesterol oxidase in Bifidobacterium longum under the control of 16S rRNA gene promoter of bifidobacteria. AB - We have constructed a constitutive high-level-expression vector for the genus Bifidobacterium and used it to express cholesterol oxidase from Streptomyces coelicola. The promoter region of the 16S rRNA gene was amplified by inverse PCR and used for the construction of pBES16PR. The optimal ribosome-binding site (RBS) for Bifidobacterium was incorporated in pBES16PR. In order to test the efficacy of this expression vector, we constructed pBES16PR-CHOL with the structural gene for cholesterol oxidase under the control of the 16S rRNA promoter, and used it to transform Bifidobacterium longum. The gene was successfully expressed and high level of cholesterol oxidase activity was obtained in B. longum. This is the first report of an expression vector for the genus Bifidobacterium using a 16S rRNA gene promoter and successful expression of cholesterol oxidase. PMID- 17849089 TI - Cerebral hemorrhage and vasospasm in a child with congenital heart disease. AB - INTRODUCTION: Intracerebral hemorrhages are relatively rare events in children and cerebral vasospasm after such hemorrhages is even more unusual. Children with structural congenital heart disease are particularly at risk for both thrombotic and embolic events but not to isolated hemorrhages. DISCUSSION: We report a case of cerebral vasospasm in a child with structural congenital heart disease after a cerebral hemorrhage. CONCLUSION: This case illustrates that this rare occurrence must be swiftly recognized and treated in order to maximize clinical outcome. PMID- 17849091 TI - [Significance of nutrition in obesity]. AB - The goal of good concepts for treating obesity is to achieve sustained changes in lifestyle. Formula diets are in fact superior to hypocaloric diets, but the results of diet only approaches are consistently disappointing. Formula diets or very low calorie diets should thus be undertaken in conjunction with an overall therapeutic concept under a physician's supervision together with psychological and nutritional education as well as guidance in exercise therapy. These treatment strategies can be carried out successfully in the outpatient setting. On a long-term basis, reducing the costs of health care will only be feasible by implementing prevention programs during childhood and adolescence. Preventive measures focusing on nutrition should lay the foundation in kindergartens and schools to control the epidemic-like spread of obesity. PMID- 17849092 TI - [Stroke]. PMID- 17849090 TI - [Therapy of systemic sclerosis]. AB - The therapy of systemic sclerosis (SSc) remains a challenge for dermatology, rheumatology, internal medicine, and other disciplines. Organ involvement, above all kidney and lungs, is a key therapeutic issue. The current developments in organ-specific therapy are the main topic of the article. Finally, possibilities of disease-modifying drugs and value of HSCT are discussed. PMID- 17849093 TI - [Stent and surgery for symptomatic carotid stenosis. SPACE study results]. AB - The SPACE trial compared risk and effectiveness of stent-supported angioplasty (CAS) vs carotid endarterectomy (CEA) using a noninferiority design in patients with symptomatic stenoses. Intention-to-treat analysis of the entire study population of 1,214 patients showed that primary endpoint events (ipsilateral stroke or death between randomisation and day 30) occurred in 6.92% of the CAS group and 6.45% of the CEA group. The 95% confidence interval (CI) of the absolute risk difference ranged from -1.94% to +2.87%, therefore the noninferiority was not proven. The same was true for the analysis of protocols. No significant differences between the two treatment methods were found in primary or any of the secondary endpoints. There were also no differences in short-term prevention. The endpoint 'ipsilateral ischemic stroke or vascular death between randomisation and 6 months' occurred in 7.4% of the CAS and 6.5% of the CEA patients (odds ratio 1.16, 95% confidence interval 0.74-1.82). Instent restenoses were significantly more common in the CAS group (4.6% vs 2.2%, odds ratio 2.14, 95% CI 1.10-4.18). Surgery remains the gold standard in treatment of patients with symptomatic carotid artery stenosis. Stent-supported angioplasty can be an alternative only in the hands of an experienced interventionalist with proven low periprocedural complication rate. PMID- 17849094 TI - [The structural dynamic approach: its psychopathologic origin and application to considerations of personality]. AB - Concepts based on brain structure and function with a tendency towards elimination of the subject have assumed a position of central importance in modern psychiatry. With respect to structural dynamics, the primary role in relating to others is played by each person's internal world. Psychic structure is a precondition of our intentions and personal identity. In psychopathology the three basic functions autopractice, desactualisation, and activation had been differentiated as contributing to the psyche as a whole. Their application is expanded to an anthropological conceptualisation. PMID- 17849095 TI - Support vector machine regression for the prediction of maize hybrid performance. AB - Accurate prediction of the phenotypical performance of untested single-cross hybrids allows for a faster genetic progress of the breeding pool at a reduced cost. We propose a prediction method based on epsilon-insensitive support vector machine regression (epsilon-SVR). A brief overview of the theoretical background of this fairly new technique and the use of specific kernel functions based on commonly applied genetic similarity measures for dominant and co-dominant markers are presented. These different marker types can be integrated into a single regression model by means of simple kernel operations. Field trial data from the grain maize breeding programme of the private company RAGT R2n are used to assess the predictive capabilities of the proposed methodology. Prediction accuracies are compared to those of one of today's best performing prediction methods based on best linear unbiased prediction. Results on our data indicate that both methods match each other's prediction accuracies for several combinations of marker types and traits. The epsilon-SVR framework, however, allows for a greater flexibility in combining different kinds of predictor variables. PMID- 17849096 TI - Acute suppression of VLDL1 secretion rate by insulin is associated with hepatic fat content and insulin resistance. AB - AIMS/HYPOTHESIS: Overproduction of VLDL(1) seems to be the central pathophysiological feature of the dyslipidaemia associated with type 2 diabetes. We explored the relationship between liver fat and suppression of VLDL(1) production by insulin in participants with a broad range of liver fat content. METHODS: A multicompartmental model was used to determine the kinetic parameters of apolipoprotein B and TG in VLDL(1) and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol during a hyperinsulinaemic-euglycaemic clamp in 20 male participants: eight with type 2 diabetes and 12 control volunteers. The participants were divided into two groups with low or high liver fat. All participants with diabetes were in the high liver-fat group. RESULTS: The results showed a rapid drop in VLDL(1)-apolipoprotein B and -triacylglycerol secretion in participants with low liver fat during the insulin infusion. In contrast, participants with high liver fat showed no significant change in VLDL(1) secretion. The VLDL(1) suppression following insulin infusion correlated with the suppression of NEFA, and the ability of insulin to suppress the plasma NEFA was impaired in participants with high liver fat. A novel finding was an inverse response between VLDL(1) and VLDL(2) secretion in participants with low liver fat: VLDL(1) secretion decreased acutely after insulin infusion whereas VLDL(2) secretion increased. CONCLUSIONS/INTERPRETATION: Insulin downregulates VLDL(1) secretion and increases VLDL(2) secretion in participants with low liver fat but fails to suppress VLDL(1) secretion in participants with high liver fat, resulting in overproduction of VLDL(1). Thus, liver fat is associated with lack of VLDL(1) suppression in response to insulin. PMID- 17849097 TI - Use of bladder pressure to correct for the effect of expiratory muscle activity on central venous pressure. AB - OBJECTIVE: To assess whether subtracting the expiratory change in intra-abdominal (bladder) pressure (Delta IAP) from central venous pressure (CVP) provides a reliable estimate of transmural CVP in spontaneously breathing patients with expiratory muscle activity. DESIGN AND SETTING: Prospective observational study in a medical ICU. PATIENTS: Twenty-four spontaneously breathing patients with central venous and bladder catheters: 18 with no clinical evidence of active expiration (group 1) and 6 with active expiration (group 2). INTERVENTIONS: Patients in group 1 were coached to change their breathing pattern to one of active expiration for several breaths; those in group 2 were asked to sip water through a straw to briefly interrupt active expiration. MEASUREMENTS AND RESULTS: During active expiration end-expiratory CVP (uncorrected CVP) and Delta IAP were measured; Delta IAP was subtracted from uncorrected CVP to obtain corrected CVP. End-expiratory CVP during relaxed breathing (best CVP) was assumed to represent the best estimate of transmural CVP. The absolute difference between corrected CVP and best CVP was much less than the difference between uncorrected CVP and best CVP (2.3+/-2.0 vs. 12.5+/-4.7 mmHg). CONCLUSIONS: In patients with active expiration, subtracting Delta IAP from end-expiratory CVP yields a more reliable (and lower) estimate of transmural CVP than does the uncorrected CVP value. PMID- 17849100 TI - Real-time detection of L-glutamate released from C6 glioma cells using a modified enzyme-luminescence method. AB - There is an increasing interest in new strategies to detect neurotransmitters released from nerve cells in real time for brain science, drug assessment, and so on. Previously we reported real-time monitoring of dopamine release from nerve model cells by enzyme-catalyzed luminescence measurement with tyramine oxidase and peroxidase. In the present study, the system was modified with glutamate oxidase instead of tyramine oxidase to detect L-glutamate sensitively ( approximately 10 nM) and rapidly with high temporal resolution (<1 s). We applied this modified method successfully to perform real-time monitoring of L-glutamate release from brain model cell (C6 glioma cell) using a luminescence plate reader upon stimulation with high concentration of KCl (>10 mM) or 5-hydroxytryptamine (>1 microM). The measurement solution was not toxic and therefore the L-glutamate release from the cell was measured by the second stimulation after exchanging the measurement solution. We conclude that the developed monitoring system is suitable for real-time detection of dynamic L-glutamate release from nerve cells in vitro and will be suitable for application in assessment of drugs acting on the nervous system. PMID- 17849098 TI - Cocaine increases immunoglobulin heavy chain binding protein and caspase-12 expression in the rat dorsal striatum. AB - RATIONALE: Cocaine increases endoplasmic reticulum (ER) stress protein expression via glutamate and dopamine receptor activation in the dorsal striatum. OBJECTIVES: The present study was performed to investigate ER stress response in the dorsal striatum in response to acute or repeated cocaine stimulation. It was hypothesized that cocaine upregulates the ER stress protein immunoglobulin heavy chain binding protein (BiP) and the ER stress-associated protein caspase-12 via N methyl-D-aspartate (NMDA) and D1 dopamine receptor activation. MATERIALS AND METHODS: Western immunoblot and immunohistochemical analyses were mainly performed to test this hypothesis in the rat dorsal striatum. RESULTS: The results showed that BiP and caspase-12 immunoreactivities were significantly increased at 30, 60, and 120 min after acute or repeated intraperitoneal (i.p.) injections of three doses (10, 20, 40 mg/kg) of cocaine for seven consecutive days. Intrastriatal (i.s.) infusion of the selective NMDA antagonist MK801 (2 nmol) or AP5 (2 nmol) significantly attenuated the increase in the immunoreactivity of caspase-12 in the dorsal striatum induced by repeated, but not acute, cocaine (20 mg/kg) administration. However, i.p. injection of the selective D1 antagonist SCH23390 (0.1 mg/kg) significantly attenuated the increase in the immunoreactivity of caspase-12 in the dorsal striatum induced by both acute and repeated cocaine (20 mg/kg) stimulation. CONCLUSION: These findings suggest that acute or repeated cocaine administration can cause ER stress response in the dorsal striatum in which NMDA and D1 dopamine receptors participate in the mediation of the process. PMID- 17849101 TI - Characterization of cellular chemical dynamics using combined microfluidic and Raman techniques. AB - The integration of a range of technologies including microfluidics, surface enhanced Raman scattering and confocal microspectroscopy has been successfully used to characterize in situ single living CHO (Chinese hamster ovary) cells with a high degree of spatial (in three dimensions) and temporal (1 s per spectrum) resolution. Following the introduction of a continuous flow of ionomycin, the real time spectral response from the cell was monitored during the agonist-evoked Ca(2+) flux process. The methodology described has the potential to be used for the study of the cellular dynamics of a range of signalling processes. PMID- 17849102 TI - A new highly specific and robust yeast androgen bioassay for the detection of agonists and antagonists. AB - Public concern about the presence of natural and anthropogenic compounds which affect human health by modulating normal endocrine functions is continuously growing. Fast and simple high-throughput screening methods for the detection of hormone activities are thus indispensable. During the last two decades, a panel of different in vitro assays has been developed, mainly for compounds with an estrogenic mode of action. Here we describe the development of an androgen transcription activation assay that is easy to use in routine screening. Recombinant yeast cells were constructed that express the human androgen receptor and yeast enhanced green fluorescent protein (yEGFP), the latter in response to androgens. Compared with other reporters, the yEGFP reporter protein is very convenient because it is directly measurable in intact living cells, i.e., cell wall disruption and the addition of a substrate are not needed. When yeast was exposed to 17beta-testosterone, the concentration where half-maximal activation is reached (EC(50)) was 50 nM. The relative androgenic potencies, defined as the ratio between the EC(50) of 17beta-testosterone and the EC(50) of the compound, of 5alpha-dihydrotestosterone, methyltrienolone, and 17beta-boldenone are 2.3, 1.4, and 0.15 respectively. The results presented in this paper demonstrate that this new yeast androgen bioassay is fast, sensitive, and very specific and also suited to detect compounds that have an antiandrogenic mode of action. PMID- 17849103 TI - Discrimination between wild-type and ampicillin-resistant Escherichia coli by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. AB - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was optimized to discriminate between wild-type and ampicillin resistant Escherichia coli. Only ampicillin-resistant E. coli displayed an m/z approximately 29,000 peak, which was confirmed as beta-lactamase by in-gel digestion followed by peptide mass fingerprinting. Rapid MALDI-TOF MS detection of antibiotic-resistance could fulfill an important clinical need, providing critical phenotypic information beyond genus-species identification. PMID- 17849104 TI - Optimization of direct whole blood PCR amplification with applications on a static thermostat chip. AB - In this paper, direct whole blood PCR amplifications on a static chip thermostat without sample purifications are demonstrated; in these amplifications, problems such as cross-interferences and contaminations could be avoided. The amplification conditions, such as the compositions of reagents and thermal programs, were investigated systematically by a GeneAmp PCR system with a native p53 gene segment (about 543 bp) of human genome and an exterior lambda DNA segment (about 500 bp) as targets. Direct amplifications of p53 and K-ras (about 157 bp) gene segments from 0.5 microL blood samples were successfully demonstrated by a static PCR chip with an indium tin oxide glass substrate. The chip thermostat has a typical size of 25 mm x 25 mm, and a polyethylene tube was used as the PCR vial on the glass surface of the chip. Fuzzy proportional integration-differentiation algorithms were adopted in temperature controls of the chip with an aid of a micro-Pt100 sensor. In the direct PCR with the thermostat chip, the whole process only involves automatic thermal programs. This work demonstrated that a chip PCR for field test without desktop facilities is possible either for a point of care test or for forensic analysis. PMID- 17849105 TI - At-line coupling of UPLC to chip-electrospray-FTICR-MS. AB - Since highly sensitive on-line coupling of UPLC with FTICR-MS is technically infeasible due to their different scan rates, at-line coupling of these techniques was developed for rapid analysis. To enable cutting of one peak of the chromatogram into one fraction, several conditions and relationships were investigated, e.g. the optimum volume of the inserted delay loop, the relationship between retention time, loop outlet drop speed, individual drop volume versus mobile phase composition under constant speed, and linear solvent strength gradient elution modes. Good and reproducible results were achieved applying UPLC as an efficient separation and fast fractionation tool before the FTICR-MS measurements. A chip-based nanoelectrospray ionization system was employed which was perfectly suited to handling the small-volume fractions and was thus chosen for the at-line coupling. The method was initially applied to spiked extracts of cell-free bacterial culture supernatants in which bacterial signalling compounds, namely N-acyl homoserine lactones (AHL), were detected. Good reproducibility and high recovery was observed. Afterwards, a culture supernatant of Erwinia sp. JX3.2, a putative AHL producer, was investigated and N hexanoyl-homoserine lactone was determined as a possible signalling molecule. More reliable assignments were achieved by use of at-line coupling of UPLC and FTICR-MS compared with off-line measurements. PMID- 17849106 TI - Determination of chlormequat in pig serum and sow milk by LC-MS/MS. AB - Chlormequat is a plant growth regulator widely used on cereals, and there is general concern that it may impair human fertility. A LC-MS/MS method for the analysis of chlormequat in milk and serum was developed and validated in connection with an investigation on the effect of chlormequat on pig reproduction. Validation of the method was based on recovery tests at three spiking levels, determined as double determinations and repeated at least four times. Samples were extracted with methanol-water-acetic acid, centrifuged, filtrated and determined by LC-MS/MS. The mean recoveries were in the range 80 110%, and the LOD was 0.2 ng/g for serum and 0.3 ng/g for milk. The values for repeatability and reproducibility were within 2/3 of the limits given by the Horwitz equation. Samples of pig serum (59) and sow milk (27) were analyzed using the method. Chlormequat was determined in four milk samples in the range of 0.4 ng/g to 1.2 ng/g and in all serum samples in the range of 0.2 ng/g-4.0 ng/g. PMID- 17849107 TI - Collision avoidance behavior as a function of aging and tennis playing. AB - Daily living often requires pedestrians and drivers to adapt their behavior to the displacement of other objects in their environment in order to avoid collision. Yet little research has paid attention to the effect of age on the completion of such a challenging task. The purpose of this study was to examine the relationship between age and collision avoidance skill and whether a sporting activity affects this. Three age groups (20-30, 60-70, and 70-80 years) of tennis players and non-players launched a projectile toward a target in order to hit it before it was hit by another "object" (a stimulus represented by apparent motion of lights). If the participant judged that time-to-collision (TTC) of the moving stimulus was not long enough for him/her to launch the projectile in time to arrive before the stimulus, the participant had to inhibit the launching. Results showed that for the non-players the number of errors in the 70-80 year-old group was significantly higher than those of the 20-30 and 60-70 year-old groups, which did not differ from each other. However, this increase was not observed in the 70 80 year-old tennis players, demonstrating a beneficial effect of playing tennis on collision avoidance skill. Results also revealed that the older groups of both tennis players and non-players were subject to the typical age-related increase in response time. Additional analyses indicated that the 70-80 year-old non players did not adjust their actions to these age-related changes in response time. The older tennis-playing participants, however, were more likely to adjust collision avoidance behavior to their diminished response times. PMID- 17849108 TI - Differences in coding provided by proprioceptive and vestibular sensory signals may contribute to lateral instability in vestibular loss subjects. AB - One of the signatures of balance deficits observed in vestibular loss subjects is the greater instability in the roll compared to pitch planes. Directional differences in the timing and strengths of vestibular and proprioceptive sensory signals between roll and pitch may lead to a greater miscalculation of roll than pitch motion of the body in space when vestibular input is absent. For this reason, we compared the timing and amplitude of vestibular information, (observable in stimulus-induced head accelerations when subjects are tilted in different directions), with that of proprioceptive information caused by stimulus induced rotations of ankle and hip joints [observable as short latency (SL) stretch responses in leg and trunk muscle EMG activity]. We attempted to link the possible mode of sensory interaction with the deficits in balance control. Six subjects with bilaterally absent vestibular function and 12 age-matched controls were perturbed, while standing, in 8 directions of pitch and roll support surface rotation in random order. Body segment movements were recorded with a motion analysis system, head accelerations with accelerometers, and muscle activity with surface EMG. Information on stimulus pitch motion was available sequentially. Pitch movements of the support surface were best coded in amplitude by ankle rotation velocity, and by head vertical linear acceleration, which started at 13 ms after the onset of ankle rotation. EMG SL reflex responses in soleus with onsets at 46 ms provided a distal proprioceptive correlate to the pitch motion. Roll information on the stimulus was available simultaneously. Hip adduction and lumbo-sacral angular velocity were represented neurally as directionally specific short latency stretch and unloading reflexes in the bilateral gluteus medius muscles and paraspinal muscles with onsets at 28 ms. Roll angular accelerations of the head coded roll amplitude and direction at the same time (31 ms). Significant differences in amplitude coding between vestibular loss subjects and controls were only observed as a weaker coding between stimulus motion and head roll and head lateral linear accelerations. The absence of vestibular inputs in vestibular loss subjects led to characteristic larger trunk in motion in roll in the direction of tilt compared to pitch with respect to controls. This was preceded by less uphill flexion and no downhill extension of the legs in vestibular loss subjects. Downhill arm abduction responses were also greater. These results suggest that in man vestibular inputs provide critical information necessary for the appropriate modulation of roll balance-correcting responses in the form of stabilising knee and arm movements. The simultaneous arrival of roll sensory information in controls may indicate that proprioceptive and vestibular signals can only be interpreted correctly when both are present. Thus, roll proprioceptive information may be interpreted inaccurately in vestibular loss subjects, leading to an incorrect perception of body tilt and insufficient uphill knee flexion, especially as cervico-colic signals appear less reliable in these subjects as an alternative sensory input. PMID- 17849109 TI - Visuo-motor learning with combination of different rates of motor imagery and physical practice. AB - Sports psychology suggests that mental rehearsal facilitates physical practice in athletes and clinical rehabilitation attempts to use mental rehearsal to restore motor function in hemiplegic patients. Our aim was to examine whether mental rehearsal is equivalent to physical learning, and to determine the optimal proportions of real execution and rehearsal. Subjects were asked to grasp an object and insert it into an adapted slot. One group (G0) practiced the task only by physical execution (240 trials); three groups imagined performing the task in different rates of trials (25%, G25; 50%, G50; 75%, G75), and physically executed movements for the remaining trials; a fourth, control group imagined a visual rotation task in 75% of the trials and then performed the same motor task as the others groups. Movement time (MT) was compared for the first and last physical trials, together with other key trials, across groups. All groups learned, suggesting that mental rehearsal is equivalent to physical motor learning. More importantly, when subjects rehearsed the task for large numbers of trials (G50 and G75), the MT of the first executed trial was significantly shorter than the first executed trial in the physical group (G0), indicating that mental practice is better than no practice at all. Comparison of the first executed trial in G25, G50 and G75 with the corresponding trials in G0 (61, 121 and 181 trials), showed equivalence between mental and physical practice. At the end of training, the performance was much better with high rates of mental practice (G50/G75) compared to physical practice alone (G0), especially when the task was difficult. These findings confirm that mental rehearsal can be beneficial for motor learning and suggest that imagery might be used to supplement or partly replace physical practice in clinical rehabilitation. PMID- 17849111 TI - Primary intradural mesenchymal chondrosarcoma of the spine in a child. AB - We report a primary intradural mesenchymal chondrosarcoma of the spine in a 3 year-old girl. MRI revealed a markedly enhancing oval mass associated with focal areas of low signal intensity extending from T11 to L1. The lesion was located posterolateral to the right side of the spinal cord, pushing the conus medullaris and cauda equina anteriorly and to the left. The adjacent spinal cord also showed serpiginous areas of flow void. The mass was completely removed. Microscopic examination and immunohistochemical studies confirmed the diagnosis of mesenchymal chondrosarcoma. The patient was free of symptoms after surgery. PMID- 17849112 TI - Production of ascorbic acid glucoside by alginate-entrapped mycelia of Aspergillus niger. AB - The mycelia of Aspergillus niger, cultivated in a medium containing 45 g l(-1) maltose, 66 g l(-1) yeast extract, and 5 g l(-1) K(2)HPO(4) at 30 degrees C and 200 rpm, were used as a biocatalyst in the glucosylation of ascorbic acid. Free mycelia from 3-day-old culture, when used in a 6-h reaction with maltose as the acyl donor, gave 16.07 g l(-1) ascorbic acid glucoside corresponding to a volumetric productivity of 2.68 g l(-1) h(-1) and a conversion of 67%. Mycelia from 3-day-old cultures were entrapped in calcium alginate beads and used as a catalyst in the glucosylation of ascorbic acid. An ascorbic acid-to-maltose molar ratio of 1:9 was found to be optimum, and the conversion reached 75% after 12 h. The concentration of ascorbic acid glucoside produced at this molar ratio was 17.95 g l(-1), and the productivity was 1.5 g l(-1) h(-1). The biocatalyst was repeatedly used in a fixed bed bioreactor for the synthesis of ascorbic acid glucoside and approximately 17 g l(-1) of ascorbic acid glucoside corresponding to a volumetric productivity of 1.42 g l(-1) h(-1) was produced in each use. The conversion was retained at 70% in each use. The entrapped mycelia also exhibited exceptionally high reusability and storage stability. The product was purified to 85% by anion exchange and gel permeation chromatography with a final yield of 75%. PMID- 17849113 TI - Sensitivity and specificity of plain radiographic features of peripheral enthesopathy at major sites in psoriatic arthritis. AB - BACKGROUND: It has been proposed that the defining difference between rheumatoid arthritis and spondyloarthropathy (including psoriatic arthritis) is the initial pathological lesion where the emphasis in psoriatic arthritis is on the enthesis and in rheumatoid arthritis on the synovium. Classical radiological descriptions of seronegative spondyloarthropathy include enthesopathy at major entheseal insertions characterised by erosions and exuberant new bone formation. In this study, the plain radiographic features of spondyloarthropathy are compared between psoriatic arthritis, other spondyloarthropathies and rheumatoid arthritis. METHODS: The CASPAR study collected clinical, radiological and laboratory data on 588 patients with physician diagnosed psoriatic arthritis and 525 controls with other inflammatory arthritis, 70% of which had rheumatoid arthritis. Plain radiographs of the pelvis and heels were part of the study protocol, although radiographs of other potential entheseal sites such as the knee, elbow and shoulder, were interpreted if available. All radiographs were read blind by two observers working in tandem. RESULTS: Significant differences in entheseal erosion and entheseal new bone formation were found between psoriatic arthritis, ankylosing spondylitis, undifferentiated spondyloarthropathy, rheumatoid arthritis and other diagnoses (entheseal erosion, chi-squared 20.8, p=0.008; entheseal new bone formation, chi-squared 24.5, p=0.001). These differences were mainly due to a higher proportion of these features in ankylosing spondylitis. No differences in the plain radiographic features of enthesopathy were found between psoriatic arthritis and rheumatoid arthritis except in the case of entheseal new bone formation at sites of attachment of inguinal ligament, sartorius and rectus femoris muscles to the ilium (OR 3.01, 95% CI 1.13-8.02). Very few subjects with symptomatic heel involvement had radiographic changes and minimal differences were found between those with and without symptoms in terms of new bone formation and erosion at either calcaneal site. CONCLUSIONS: New bone formation and erosion at major entheseal sites is most commonly seen in ankylosing spondylitis. Plain radiographic features of major enthesopathy are poor discriminators between psoriatic arthritis and rheumatoid arthritis. PMID- 17849114 TI - The radiological manifestations of intramuscular haemangiomas in adults: magnetic resonance imaging, computed tomography and ultrasound appearances. AB - OBJECTIVE: Intramuscular haemangiomas in adults may appear similar to soft tissue sarcomas on imaging. This study evaluates the imaging characteristics of intramuscular haemangiomas on magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound. SUBJECTS AND METHODS: Retrospective review of medical records, imaging and pathology details of 34 patients presenting with intramuscular haemangiomas was performed. Age of patient, size, site of lesion and type of imaging was recorded. Lesions were evaluated for calcification, presence of fat, outline, texture, vascularity, enhancement and involvement of local structures. RESULTS: There were 12 male and 22 female patients aged between 9 years and 90 years (mean 39 years). Twenty-two lesions involved muscles of the extremities and 12 involved muscles of the trunk. Mean duration of the lesions was long: 59.3 months (range 3-240 months), with an average size of 7.5 cm (1.5 15 cm). Imaging comprised 27 MR studies, seven CT scans, 19 ultrasounds, and eight plain films. All lesions were well defined, lobulated and heterogeneous. None showed local invasion. On MRI and CT, 93-100% showed the presence of fat and 100% showed vascular channels and enhancement on MRI, CT and ultrasound. Phleboliths were seen on four plain films (50%) and on the corresponding MR images. On MRI, 70% of lesions had mildly hyperintense signal on T1-weighted sequences and 96% had hyperintense signal on T2-weighted sequences (relative to skeletal muscle). Histopathology confirmed diagnosis in all cases, showing the presence of fat, medium/large vessels and skeletal muscle. CONCLUSION: Intramuscular haemangiomas have characteristic appearances on MRI, CT and ultrasound. Long history, presence of fat, calcification and internal vessels should alert the radiologist to this diagnosis prior to biopsy. PMID- 17849115 TI - PET-CT is only one option. PMID- 17849116 TI - Autologous peripheral blood stem cell transplantation in a patient with POEMS syndrome. PMID- 17849117 TI - Kinetics and apoptotic profile of circulating endothelial cells as prognostic factors for induction treatment failure in newly diagnosed acute myeloid leukemia patients. AB - The circulating endothelial cells (CEC) are proposed to be a noninvasive marker of angiogenesis. Recent data suggest that endothelial cells may enhance the survival and proliferation of leukemic blasts and mediate chemotherapy resistance in acute myeloid leukemia (AML). We analyzed CEC count by the four-color flow cytometry in AML and healthy subjects. We evaluated the kinetics of mature CEC, both resting (rCEC) and activated (aCEC), as well as progenitor (CEPC) and apoptotic CEC (CEC(AnnV+)) in AML patients treated with standard chemotherapy and their influence on response to treatment and overall survival. We found significantly higher numbers of aCEC, rCEC, CEPC, and CEC(AnnV+) in AML patients than in healthy controls. The elevated CEPC and absolute blood counts in peripheral blood as well as the low CEC(AnnV+) number were associated with higher probability of induction treatment failure. aCEC, rCEC, CEPC, and CEC(AnnV+) counts determined in complete remission (CR) were significantly lower than those found at diagnosis. In those CR patients, a significant decrease in the CEC count and increase in the number of CEC(AnnV+) were observed already 24h after the first dose of chemotherapy. In refractory AML, the aCEC, rCEC, CEPC, and CEC(AnnV+) counts assessed before and after induction chemotherapy did not differ significantly, and a significant decrease in CEC count and increase in CEC(AnnV+) number were noted only after the last dose of chemotherapy. The number of CEC is significantly higher in AML patients than in healthy subjects and correlates with response to treatment. The evaluation of CEC kinetics and apoptotic profile may be a promising tool to select AML patients with poor response to chemotherapy who may benefit from antiangiogenic therapies. PMID- 17849118 TI - Successful amelioration of oxaliplatin-induced hyperexcitability syndrome with the antiepileptic pregabalin in a patient with pancreatic cancer. AB - BACKGROUND: Oxaliplatin, a platinum derivative used in the treatment of gastrointestinal cancers, has been associated with sensory neuropathies and, more infrequently, a neuromyotonia-like hyperexcitability syndrome. We present a case of hyperexcitability syndrome that developed during the treatment of pancreatic cancer with oxaliplatin and gemcitabine (GEMOX) that was successfully treated with pregabalin. CASE PRESENTATION: A 54-year-old woman was undergoing chemotherapy with gemcitabine and oxaliplatin (GEMOX) for stage II-B pancreatic adenocarcinoma. On the third day of her fourth cycle, she presented with twitching of eyelids and tremors of hands. This twitching started bilaterally on the eyelids, followed by teeth jittering, hand shaking, and slurring of speech. A thorough neurological exam revealed no abnormalities except increased tone of both hands-she had difficulty opening her hand after closing it for a hand-grip. She was given a dose of 1 g of IV magnesium sulfate and 1 g of IV calcium gluconate, and 50 mg of IV diphenhydramine. In addition to reassurance, pregabalin was prescribed for these myotonic symptoms at a dosage of 50 mg by mouth three times daily. Improvement occurred in these symptoms within 12 h and she was almost asymptomatic within 72 h. CONCLUSION: Oxaliplatin causes a unique spectrum of acute neurological toxicities that have not been observed in patients receiving either cisplatin or carboplatin. Clinically, sensory alterations are most prominent, particularly cold-induced and perioral paresthesias. Other symptoms, such as cramps, jaw stiffness, voice changes, ptosis, and visual field changes suggest that motor nerves or muscles may also be involved (hyperexcitability). Hyperexcitability syndrome, distinct from cold-induced paresthesias and sensory neuropathy, is a rare complication of oxaliplatin chemotherapy; and up to date no pharmacotherapy has been successful in treating these symptoms. This is the first report of the successful amelioration of this syndrome with the antiepileptic pregabalin. PMID- 17849119 TI - In vitro evaluation of the effects of gefitinib on the modulation of cytotoxic activity of selected anticancer agents in a panel of human ovarian cancer cell lines. AB - PURPOSE: This study was conducted to determine the in vitro optimal combination of selected anticancer agents with gefitinib and evaluate its effect on the expression of correlative biological targets in the cell-signaling pathway. In addition, the effect of gefitinib on the expression of ATP-binding cassette (ABC) transport proteins was evaluated. METHODS: Growth inhibition assays were conducted in five human ovarian cancer cell lines to evaluate the activity of selected anticancer agents in combination with gefitinib compared to each alone. Enzyme linked immunosorbant assay (ELISA) assessed the presence of pEGFR in treated and untreated cells. Expression of correlative biological targets in the cell-signaling pathway was completed by immunoblotting. RT-PCR was used to characterize the expression ABC transport proteins. RESULTS: This in vitro study confirmed gefitinib did not have significant cytotoxic activity, the combination of gefitinib with other chemotherapy drugs demonstrated improved in vitro cytotoxic activity in platinum sensitive ovarian cancer cell lines. Suppression of pAKT and p-erk activation in cells treated with combination of cisplatin and gefitinib was observed and suggests the role of gefitinib inhibition of proliferative cell signaling pathway. CONCLUSION: This data suggests that EGFR inhibitors, such as gefitinib, have the potential to modulate common mechanisms of drug resistance and may have a role in optimizing chemotherapy regimens for the treatment of ovarian cancer. PMID- 17849120 TI - The complete classification for dynamics in a homosexually-transmitted disease model. AB - A sexually-transmitted disease model for two strains of pathogen in a one-sex, heterogeneously-mixing population was proposed by Li et al. in (J Math Biol 10:1037-1052, 1986). The sufficient and necessary conditions for coexistence and the sufficient conditions for stability of the boundary equilibria were provided. This paper will present a thorough classification of dynamics for this model in terms of the first and second so called reproductive numbers of infection in strains I and J. This classification not only solves a conjecture proposed in (Li et al., J Math Biol 10:1037-1052, 1986) but also gives the sufficient and necessary conditions for the competitive exclusion. PMID- 17849121 TI - [Pathology websites in the World Wide Web. A guide for a specific research of pathology information on the Internet]. AB - Being a global information network, the internet has becoming increasingly important for pathologists as a medium for professional communication and information. Although a large number of pathology-specific websites (PSWs) are accessible on the internet, the potentials of PSWs are still barely known. Since there is no global catalog for all the pathology websites, certain PSWs are difficult to find on the internet. PSWs offer lavishly illustrated education material for undergraduates and postgraduates in pathology, but may also be very useful as reference books or as an instrument of continuing medical education (CME) for experienced pathologists. The spectrum of PSW media comprises electronic training manuals, journals, case collections, photo-archives, and even complete section series of virtual microscopy. PSWs are available at any time, can be updated permanently and linked to further online sources of information. We demonstrate how to find PSWs and present an annotated list of some 100 of the best PSWs. PMID- 17849122 TI - Intramedullary spinal cord cavernous angioma in children: case report and literature review. AB - INTRODUCTION: Intramedullary cavernous angiomas (ImCA) of the spinal cord are very uncommon malformations especially in the pediatric population where only ten cases have yet been reported within the available literature. CASE REPORT: In this paper, the authors report the case of a 12-year-old girl presenting with a T11 level hematomyelia because of a cavernous angioma. Microsurgical excision was performed with good clinical outcome and no magnetic resonance imaging evidence of residual cavernoma 30 months later. DISCUSSION: Despite the small number of cases reported in children, this one contributes to the literature identifying special features of presentation and management of ImCA for pediatric patients. Because a higher risk of recurrent bleeding has been demonstrated for ImCA, with dramatic clinical consequences, microsurgical removal remains the only definitive treatment. PMID- 17849124 TI - [New aspects of the pathogenesis of systemic lupus erythematosus]. AB - To date, the pathogenesis of systemic lupus erythematosus (SLE) is only partially understood. A characteristic feature of this disease is the occurrence of antibodies against nuclear antigens. Further, SLE is characterized by a type-I interferon gene signature. A dysregulation of apoptosis and phagocytosis of apoptotic cells is discussed as a central pathogenetic mechanism in the development of SLE. Several publications in recent years have described an accumulation of autoantigens within apoptotic cells, as well as an exposition of these antigens on the surface of apoptotic cells. During late stages of apoptosis, autoantigens are posttranslationally modified, leading to the formation of neoantigens. Subcellular fragments such as apoptotic microparticles also seem to be involved in the pathogenesis of SLE. It has been shown that microparticles contain relevant antigens and stimulate B- and T-lymphocytes. Moreover, apoptotic microparticles have the ability to stimulate plasmacytoid dendritic cells, causing a secretion of interferon alpha. These observations provide a link between dysregulation of apoptosis and phagocytosis and the type-I interferon signature observed in SLE patients. PMID- 17849125 TI - [Infliximab is ineffective against giant cell arteritis and polymyalgia rheumatica]. PMID- 17849126 TI - [Assessment of musculoskeletal pain]. AB - Persons suffering from chronic musculoskeletal pain and applying for disability claims, should be assessed according to the biopsychosocial disease model. Interdisciplinary guidelines give advice on how to proceed. The claims assessor representing somatic disciplines has to recognize those subjects whose pain is not sufficiently explainable by the extent of physical damage but show typical signs of chronification (generalization of the pain extent, further body complaints, symptoms of depression), to recommend further assessment by a psychiatric or psychosomatic specialist. Technical findings must not be overestimated or the pain complaints of the subjects rejected as deliberate feigning. The extent of the pain and the underlying (physical and psychosocial) disorders have to be assessed by a consistent description of the implications for all areas of life. PMID- 17849127 TI - [The role of rheumatologists in multidisciplinary expert opinions]. AB - Diseases of the musculoskeletal system are among the foremost reasons for premature health-related loss of employment. In giving expert opinions, physicians need a change of perspective from a therapeutic patient-doctor relationship where the well-being of the patient is important, to the expert consultant setting where the goal is to find an objective truth. Both ways of thinking demand a scientific evidence-based approach. Chronic pain syndromes often revolve around the borderline between soma and psyche. In the perception of modern pain research, a strict distinction between somatically and psychically caused pains is obsolete. In expert assessments of chronic pain a close cooperation between rheumatologist and psychiatrist is mandatory. This article focuses on the role of the rheumatologist in multidisciplinary expert assessment and also highlights some peculiarities of Swiss jurisdiction. PMID- 17849128 TI - [Obituary for professor Werner Otto]. PMID- 17849129 TI - [Transient osteoporosis of the hip in pregnancy. Successful treatment with calcitonin: a case report]. AB - Transient osteoporosis of the hip is a rare clinical disorder of unknown etiology, characterized by hip pain and functional disability that resolves spontaneously in 6-24 months. Despite a benign prognosis, the long clinical course causes prolonged disability. We report on a case of transient osteoporosis of the hip during pregnancy that was rapidly resolved with the use of calcitonin. An accurate diagnosis was made 2 months after the onset of symptoms (4 weeks postpartum) based on findings in the form of bone marrow edema of the right hip by magnetic resonance imaging. The patient received calcitonin for 8 weeks and the beneficial effect was observed after 3 weeks of therapy with full resolution of symptoms after 8 weeks of therapy (4 months after onset of symptoms). We suggest that the use of calcitonin may be considered as a therapeutic intervention to shorten the disease duration. PMID- 17849130 TI - [In memoriam Professor Dr. Med. Elisabeth Stoeber: founder of pediatric rheumatology in Garmisch-Partenkirchen]. PMID- 17849133 TI - Juvenile granulosa cell tumor of the ovary associated with hypercalcemia. AB - INTRODUCTION: Juvenile granulosa cell tumors (JGCTs) are rare ovarian neoplasms that typically occur in children and young women. While most JGCTs are diagnosed in Stage IA and can be cured by unilateral oophorectomy alone, the remainders are diagnosed in more advanced stages and may exhibit aggressive behavior despite surgery and chemotherapy. Paraneoplastic hypercalcemia occurs in 5% of ovarian malignancies with small cell and clear cell carcinoma being the commonest ovarian tumors associated with hypercalcemia. Only one case of ovarian JGCT associated with hypercalcemia has previously been documented in the literature. CASE REPORT: A 25-year-old married childless woman presented with a unilateral ovarian mass associated with profound hypercalcemia and suppressed serum parathyroid hormone intact (PTH-i) level. After rectifying the hypercalcemia with saline hydration, furosemide, and anti-hypercalcemic drugs, the patient underwent unilateral salpingo-oophorectomy that demonstrated Stage IC ovarian JGCT. The patient received adjuvant chemotherapy with three courses of BEP (bleomycin, etoposide and cisplatin) and to date, ten months after surgery, she is disease-free, eucalcemic, and menstruating normally. CONCLUSION: This is the second case reported in the literature of ovarian JGCT associated with hypercalcemia. Since serum PTH-i level was suppressed and the hypercalcemia did not recur after resection of the tumor, it is concluded that the hypercalcemia was caused by parathyroid hormone-related protein (PTH-rP) produced by the tumor. It seems that unilateral salpingo-oophorectomy followed by BEP chemotherapy is an appropriate treatment for unilateral Stage IC ovarian JGCT in women desiring to preserve ovarian function and childbearing capacity. PMID- 17849134 TI - Vulvar endometriosis in surgical scar after excision of the Bartholin gland: report of a case. AB - Endometriosis is a common gynecologic disease characterized by growth of endometrial glands and stroma outside the endometrium. Implants are most commonly found in the pelvis but can occur in many other sites. Vulvar involvement of endometriosis is extremely rare. A case of vulvar endometriosis is presented. Endometriosis was infiltrating the subcutaneous scar tissue of left labia minora after cystectomy of Bartholin gland for abscess that has recurred several times despite office-based treatment. PMID- 17849135 TI - Transvaginal bowel evisceration following pelvic floor repair. PMID- 17849136 TI - Laryngeal zoster with multiple cranial nerve palsies. AB - A young immunocompetent patient is presented with a very rare presentation of a common viral illness: herpes zoster of the left hemilarynx with sensorial and motoric neuropathy of three ipsilateral lower cranial nerves: IX, X and XI. The mucosal lesions were discovered during upper gastrointestinal endoscopy. PCR of erosional exsudate confirmed the clinical diagnosis. Antiviral therapy and corticosteroids possibly contributed to the prosperous evolution with complete healing. PMID- 17849137 TI - Status of the remaining parotid duct and gland following superficial parotidectomy. AB - The changes in Stensen's duct and remaining parotid tissue following superficial parotidectomy have not been studied previously. The aim of this clinical case control study is to describe these changes using sialography and CT-sialography techniques. Fourteen superficial parotidectomy cases underwent parotid sialography bilaterally. CT sialography was also done. Stensen's duct was patent in 11 cases (79%), and non-patent in three cases (21%). Its angle in relation to our reference line was 20 degrees in operated cases versus 37 degrees for the non operated cases. Following superficial parotidectomy, the remaining parotid tissues usually remain functional and retain drainage through Stensen's duct. Furthermore, superficial parotidectomy changes the direction of this duct. Parotid sialography and CT sialography can still be used to study the status of remaining parotid tissue following superficial parotidectomy. The post-surgical changes should be reviewed with care before interpreting these studies. PMID- 17849138 TI - An association between vascular endothelial growth factor gene promoter polymorphisms and diabetic retinopathy. AB - BACKGROUND: Diabetic retinopathy is a highly prevalent cause of visual loss in Western countries. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor implicated in the development of the proliferative stage of this disease. Reports have suggested that polymorphisms at positions -460 and 634 of the 5' untranslated region of the VEGF gene increase its basal promoter activity. METHODS: To investigate whether polymorphisms are associated with diabetic retinopathy, 215 patients with type 2 diabetes mellitus (T2DM) were enrolled. Among them, 82 subjects had proliferative diabetic retinopathy (PDR), 72 had non-proliferative diabetic retinopathy (NPDR), and 61 individuals without retinopathy served as controls. Two polymorphisms of the VEGF gene, a G-->C transversion at -634 (the G/C polymorphism) and a C-->T transition at -460 (the C/T polymorphism), were investigated by restriction fragment length polymorphism PCR and allele-specific PCR respectively. RESULTS: We did not find any association between the C/T polymorphism and diabetic retinopathy. However, the G/C polymorphism genotype distribution and the frequency of the C allele were significantly higher in the NPDR group than in control patients (OR = 1.69, 95% CI = 1.03-2.79). Analysis of the distribution of combined genotypes of the VEGF gene revealed the prevalence of the C/C-C/C genotype in NPDR patients (OR = 8.26, 95% CI = 1.79-37.99) and C/G-CC in PDR patients (OR = 3.36, 95% CI = 1.39-8.12). CONCLUSIONS: Occurrence of the -634C allele appears to be associated with increased VEGF gene promoter activity, and the G/C polymorphism might serve as a predictive factor for the development of diabetic retinopathy. PMID- 17849139 TI - Apoptosis in tumour cells photosensitized with Rose Bengal acetate is induced by multiple organelle photodamage. AB - Rose Bengal (RB) is a very efficient photosensitizer which undergoes inactivation of its photophysical and photochemical properties upon addition of a quencher group-i.e. acetate-to the xanthene rings. The resulting RB acetate (RB-Ac) derivative behaves as a fluorogenic substrate: it easily enters the cells where the native photoactive molecule is restored by esterase activities. It is known that the viability of RB-Ac-loaded cells is strongly reduced by light irradiation, attesting to the formation of intracellular RB. The aim of this study was to identify the organelles photodamaged by the intracellularly formed RB. RB-Ac preloaded rat C6 glioma cells and human HeLa cells were irradiated at 530 nm. Fluorescence confocal imaging and colocalization with specific dyes showed that the restored RB molecules redistribute dynamically through the cytoplasm, with the achievement of a dynamic equilibrium at 30 min after the administration, in the cell systems used; this accounted for a generalized damage to several organelles and cell structures (i.e. the endoplasmic reticulum, the Golgi apparatus, the mitochondria, and the cytoskeleton). The multiple organelle damage, furthermore, led preferentially to apoptosis as demonstrated by light and electron microscopy and by dual-fluorescence staining with FITC-labelled annexin V and propidium iodide. PMID- 17849140 TI - Phenotypic differences between red pulp capillary and sinusoidal endothelia help localizing the open splenic circulation in humans. AB - The distribution of capillaries, sinuses and larger vessels was investigated by immunohistology in paraffin sections of 12 adult human spleens using a panel of antibodies. Double staining for CD34 and CD141 (thrombomodulin) revealed that capillary endothelia in the cords of the splenic red pulp and at the surface of follicles were CD34(+)CD141(-), while red pulp sinus endothelia had the phenotype CD34(-)CD141(+). Only in the direct vicinity of splenic follicles did sinus endothelial cells exhibit both antigens. Thus, splenic sinuses do not replace conventional capillaries, but exist in addition to such vessels. The endothelium in arterioles, venules and larger arteries and veins was uniformly CD34(+)CD141(+). Anti-CD34 and anti-CD141 both additionally reacted with different types of splenic stromal cells. Differential staining of capillaries and sinuses may permit a three-dimensional reconstruction of serial sections to unequivocally delineate the "open" and "closed" splenic circulation in humans. PMID- 17849141 TI - Considerations on occupational medical surveillance in employees handling nanoparticles. AB - OBJECTIVES: The use of engineered nanoparticles not only offers new technical perspectives but also raises questions regarding possible health aspects for producers and users. Nanoparticles may, just by virtue of their size, exert biological effects unrelated to the chemicals they are composed of. These considerations, and results from experimental animal studies suggesting that engineered nanomaterials may pose a health hazard to employees, all underscore the need for preventive measures. In this context, the need for, the feasibility, and the appropriateness of targeted occupational medical surveillance are currently subject to debate. METHODS: We compared established concepts for the development of occupational medical surveillance programs to existing knowledge on exposures in workplaces and on health effects of nanomaterials. RESULTS: A variety of potential effect parameters have been proposed for medical surveillance of exposed personnel, such as heart rate variability, blood-clotting parameters, pro-inflammatory cytokines, etc. None of these parameters are specific, most are not validated as individual health risk indicators, and some require sophisticated equipment not routinely available. Against this background, BASF currently puts specific weight on risk assessment and exposure control in workplaces. Particle emissions are primarily avoided by manufacturing in closed systems or using effective extraction systems. Appropriate personal protective equipment has been defined for such operations where an exposure potential cannot be excluded. CONCLUSIONS: While there is presently no evidence-based foundation for "nano-specific" occupational medical screening, one can perform general medical screening with methods targeted at some of the health outcomes under discussion. The results of such examinations can provide a basis for future epidemiologic studies. Therefore, the establishment of exposure registries to enable the conduct of large-scale multi-centric prospective epidemiologic studies is recommended. PMID- 17849142 TI - Sickness absence due to depressive symptoms. AB - OBJECTIVE: There is no information on the duration of absence of depressed Dutch workers. The aim of this study was to determine the duration of sickness absence due to depressive symptoms in the working population. METHODS: In this observational study of 15% of the Dutch working population, all absence episodes (n = 9,910) starting between April 2002 and November 2005 diagnosed as depression were selected. For these episodes, Kaplan-Meier survival curves were computed. RESULTS: The mean (and median) duration of sickness absence due to depressive symptoms was 200 (179) days in men and 213 (201) days in women. In both sexes, older employees had longer absence durations. Depressive symptoms had an estimated rate of chronicity (1 year of absence) of 24%. Employees in educational and public services (232 days in men and 242 days in women), commercial services (213 days in men and 219 days in women) and health care (212 days in men and 214 days in women) had the longest mean duration of absence with depressive symptoms. Men in the industrial sector (189 days) had the shortest absence periods. Employees in large sized companies (188 days in men and 208 days in women) had shorter absence episodes as compared to companies with less than 75 employees (214 days in men and 226 days in women). CONCLUSIONS: Workers with depressive symptoms were absent for a long time. Explanations for the long duration are discussed. It is recommended to develop and apply tools for recognizing employees at risk for chronic depression. PMID- 17849143 TI - Endurance training guided individually by daily heart rate variability measurements. AB - Purpose of this study was to test utility of heart rate variability (HRV) in daily endurance exercise prescriptions. Twenty-six healthy, moderately fit males were randomized into predefined training group (TRA, n = 8), HRV-guided training group (HRV, n = 9), and control group (n = 9). Four-week training period consisted of running sessions lasting 40 min each at either low- or high intensity level. TRA group trained on 6 days a week, with two sessions at low and four at high intensity. Individual training program for HRV group was based on individual changes in high-frequency R-R interval oscillations measured every morning. Increase or no change in HRV resulted in high-intensity training on that day. If there was significant decrease in HRV (below reference value [10-day mean SD] or decreasing trend for 2 days), low-intensity training or rest was prescribed. Peak oxygen consumption (VO(2peak)) and maximal running velocity (Load(max)) were measured in maximal treadmill test before and after the training. In TRA group, Load(max) increased from 15.1 +/- 1.3 to 15.7 +/- 1.2 km h(-1) (P = 0.004), whereas VO(2peak) did not change significantly (54 +/- 4 pre and 55 +/- 3 ml kg(-1) min(-1) post, P = 0.224). In HRV group, significant increases were observed in both Load(max) (from 15.5 +/- 1.0 to 16.4 +/- 1.0 km h(-1), P < 0.001) and VO(2peak) (from 56 +/- 4 to 60 +/- 5 ml kg(-1) min(-1), P = 0.002). The change in Load(max) was significantly greater in HRV group compared to TRA group (0.5 +/- 0.4 vs. 0.9 +/- 0.2 km h(-1), P = 0.048, adjusted for baseline values). No significant differences were observed in the changes of VO(2peak) between the groups. We concluded that cardiorespiratory fitness can be improved effectively by using HRV for daily training prescription. PMID- 17849144 TI - External mechanical compression reduces regional arterial stiffness. AB - Acute aerobic and resistance exercise has been shown to reduce local muscular artery stiffness in the exercised limb while having no effect on the non exercised limb. The stimulus for these modulations may be related to local muscular compression of underlying vasculature. The purpose of this study was to examine arterial stiffness before and after a series of locally applied external mechanical compressions designed to be similar to the resistance exercise concentric/eccentric duty cycle. One rapidly inflatable cuff was placed around the upper thigh and another around the calf of the left leg in 18 healthy, young (24 +/- 1 years) participants (female n = 10). Cuffs were inflated to a supra systolic pressure of 200 mmHg for 4 s followed by a 2-s rapid deflation period. One "set" consisted of 12 inflation/deflation cycles. Six sets of 12 compression cycles were performed. Pulse wave velocity (PWV) was used to measure central stiffness (carotid to femoral) and peripheral stiffness (femoral to dorsalis pedis of both legs) before and 10 min after mechanical compressions. No change was found in central PWV (6.2 +/- 0.3 m/s to 6.3 +/- 0.3 m/s, P > 0.05). Peripheral PWV in the non-compressed leg did not change (8.5 +/- 0.4 m/s to 8.3 +/- 0.4 m/s, P > 0.05) while peripheral PWV in the compressed leg significantly decreased from pre to 10 min post (8.6 +/- 0.3 m/s to 7.6 +/- 0.3 m/s, P < 0.05). External compression reduced local artery stiffness of the compressed limb while having no effect on arterial stiffness of the non-compressed limb or central artery stiffness. PMID- 17849145 TI - Impact of hepatic vein deprivation on liver regeneration and function after major hepatectomy. AB - BACKGROUND AND AIMS: In extended liver resections, the preservation of vascular and biliary structures of the entire remnant liver is of paramount importance. The impact of venous outflow impairment and its consequences for liver regeneration and function are still a matter of debate. MATERIALS AND METHODS: Rats (n = 75) were subjected to a 90% partial hepatectomy (PH), to a 70% liver resection with narrowing of the hepatic outflow of an additional 20% parenchyma (70%+ PH) or to an anatomic 70% PH. Postoperatively hepatocyte proliferation (Ki 67), liver function and survival were assessed. Gene expression analysis for markers of regeneration was determined by in-house complementary (DNA) arrays and quantitative real-time polymerase chain reaction (RT-PCR). RESULTS: Ninety percent PH led to a greater regenerative response as shown Ki-67 compared to animals with a 70%+PH (p < 0.05). However, liver function was equally impaired in both groups. Rats with 70% PH showed a greater proliferation index with less hepatic injury and better liver function. While mortality was 0% in the group of 70% PH, rats with 90% PH and 70+PH had a reduced survival of 75% (p < 0.05) CONCLUSION: Venous outflow obstruction leads to an impairment of liver regeneration and liver function. In cases with critically small liver remnants, restoration of an adequate venous outflow may be mandatory. PMID- 17849146 TI - Oxygen and reactive oxygen species in articular cartilage: modulators of ionic homeostasis. AB - Articular cartilage is an avascular tissue dependent on diffusion mainly from synovial fluid to service its metabolic requirements. Levels of oxygen (O(2)) in the tissue are low, with estimates of between 1 and 6%. Metabolism is largely, if not entirely, glycolytic, with little capacity for oxidative phosphorylation. Notwithstanding, the tissue requires O(2) and consumes it, albeit at low rates. Changes in O(2) tension also have profound effects on chondrocytes affecting phenotype, gene expression, and morphology, as well as response to, and production of, cytokines. Although chondrocytes can survive prolonged anoxia, low O(2) levels have significant metabolic effects, inhibiting glycolysis (the negative Pasteur effect), and also notably matrix production. Why this tissue should respond so markedly to reduction in O(2) tension remains a paradox. Ion homeostasis in articular chondrocytes is also markedly affected by the extracellular matrix in which the cells reside. Recent work has shown that ion homeostasis also responds to changes in O(2) tension, in such a way as to produce significant effects on cell function. For this purpose, O(2) probably acts via alteration in levels of reactive oxygen species. We discuss the possibility that O(2) consumption by this tissue is required to maintain levels of ROS, which are then used physiologically as an intracellular signalling device. This postulate may go some way towards explaining why the tissue is dependent on O(2) and why its removal has such marked effects. Understanding the role of oxygen has implications for disease states in which O(2) or ROS levels may be perturbed. PMID- 17849147 TI - Plant defensins and virally encoded fungal toxin KP4 inhibit plant root growth. AB - Plant defensins are small, highly stable, cysteine-rich antimicrobial proteins that are thought to constitute an important component of plant defense against fungal pathogens. There are a number of such defensins expressed in various plant tissues with differing antifungal activity and spectrum. Relatively little is known about the modes of action and biological roles of these proteins. Our previous work on a virally encoded fungal toxin, KP4, from Ustilago maydis and subsequently with the plant defensin, MsDef1, from Medicago sativa demonstrated that some of these proteins specifically blocked calcium channels in both fungi and animals. The results presented here demonstrate that KP4 and three plant defensins, MsDef1, MtDef2, and RsAFP2, all inhibit root growth in germinating Arabidopsis seeds at low micromolar concentrations. We have previously demonstrated that a fusion protein composed of Rab GTPase (RabA4b) and enhanced yellow fluorescent protein (EYFP) is dependent upon calcium gradients for localization to the tips of the growing root hairs in Arabidopsis thaliana. Using this tip-localized fusion protein, we demonstrate that all four proteins rapidly depolarize the growing root hair and block growth in a reversible manner. This inhibitory activity on root and root hair is not directly correlated with the antifungal activity of these proteins and suggests that plants apparently express targets for these antifungal proteins. The data presented here suggest that plant defensins may have roles in regulating plant growth and development. PMID- 17849148 TI - A majority of cotton genes are expressed in single-celled fiber. AB - Multicellular eukaryotes contain a diversity of cell types, presumably differing from one another in the suite of genes expressed during development. At present, little is known about the proportion of the genome transcribed in most cell types, nor the degree to which global patterns of expression change during cellular differentiation. To address these questions in a model plant system, we studied the unique and highly exaggerated single-celled, epidermal seed trichomes ("cotton") of cultivated cotton (Gossypium hirsutum). By taking advantage of advances in expression profiling and microarray technology, we evaluated the transcriptome of cotton fibers across a developmental time-course, from a few days post-anthesis through primary and secondary wall synthesis stages. Comparisons of gene expression in populations of developing cotton fiber cells to genetically complex reference samples derived from 6 different cotton organs demonstrated that a remarkably high proportion of the cotton genome is transcribed, with 75-94% of the total genome transcribed at each stage. Compared to the reference samples, more than half of all genes were up-regulated during at least one stage of fiber development. These genes were clustered into seven groups of expression profiles that provided new insight into biological processes governing fiber development. Genes implicated in vesicle coating and trafficking were found to be overexpressed throughout all stages of fiber development studied, indicating their important role in maintaining rapid growth of this unique plant cell. PMID- 17849149 TI - Absence of mismatch repair deficiency in gastric lymphoma: an immunohistochemical study of mlh1 and msh2 protein expression. PMID- 17849150 TI - Parasite fauna of the bank vole (Clethrionomys glareolus) in an urban region of Germany: reservoir host of zoonotic metazoan parasites? AB - In the present study, 29 bank voles (Clethrionomys glareolus) were studied for their endo- and ectoparasite fauna. The rodents were trapped in Dormagen, a city in North Rhine-Westphalia, Germany. A total of ten different parasite species were identified: four endoparasite (four Nematoda) and six ectoparasite (three Insecta, three Arachnida) species. The predominant endoparasite was the nematode Aonchotheca murissylvatici, followed by the nematode Heligmosomum costellatum, while the flea Ctenophthalmus agyrtes was the dominant ectoparasite. C. glareolus usually carried one to five different parasite species (mean 2.2). The bank voles were infected only by Nematoda, while Digenea or Cestoda species were not detected. The present findings are in clear contrast to the results obtained in other geographical regions of Germany and Europe, where eight different Cestoda species constituted the main part of the helminth parasites in C. glareolus. In the area investigated, the bank voles harbored no zoonotic parasites, and therefore, they play not a role as potential reservoir host for these parasite species. PMID- 17849151 TI - An amine: hydroxyacetone aminotransferase from Moraxella lacunata WZ34 for alaninol synthesis. AB - An amine:hydroxyacetone aminotransferase from an isolated soil bacterium, Moraxella lacunata WZ34, was employed to synthesize alaninol in the presence of hydroxyacetone and isopropylamine in this study. The optimal carbon and nitrogen sources were glycerol and beef extract, respectively. A wide range of amino donor specificity was detected with the aminotransferase, which exhibited a relative high activity (9.83 U mL(-1)) in the presence of isopropylamine. The enzyme was the most active at pH 8.5, and showed relatively higher activity at alkaline than acidic pH. Maximum activity was achieved at 30 degrees C, and the enzyme had good thermal stability below 60 degrees C. Metal ions such as Mg(2+) had positive effect (132.6%) on the enzyme, and (aminooxy)acetic acid, a typical aminotransferase inhibitor, significantly inhibited its activity. The enzyme activity was enhanced by the addition of 0.05 mM pyridoxal-5'-phosphate (PLP). PMID- 17849152 TI - End-stage renal failure, reflux nephropathy and Feingold's syndrome. AB - Feingold's syndrome is a recognised syndrome of organ maldevelopment. Renal abnormalities are not a consistent feature. We report the case of a girl with Feingold's syndrome who had developed end-stage renal failure by the age of 6 years. We recommend that urinary tract imaging be carried out in all children suspected of having Feingold's syndrome. PMID- 17849153 TI - Rabson-Mendenhall syndrome: medullary sponge kidney, a new component. AB - Rabson-Mendenhall syndrome is a rare genetic disorder characterized by severe insulin resistance, extreme hyperinsulinemia, postprandial hyperglycemia, growth retardation, and dysmorphisms. Enlargement of the kidneys and nephrocalcinosis have been described previously. We report a 10-year-old boy who presented with gross hematuria, unilateral hydronephrosis, and the initial diagnosis of bilateral extensive medullary nephrocalcinosis. Medullary sponge kidney (MSK) was included in the differential diagnosis given the ultrasound findings. Further evaluation by intravenous pyelogram confirmed the suspected bilateral MSK. Given the patient's history of hydronephrosis due to an obstructing renal stone and MSK, urine calcium excretion was assessed and found to be markedly increased at 9.5 mg/kg per day. To our knowledge, this is the first report of Rabson Mendenhall syndrome and an association with MSK. We recommend evaluation for nephrocalcinosis, MSK, and hypercalciuria in all children diagnosed with Rabson Mendenhall syndrome. PMID- 17849154 TI - Retinoic acid enhances nephron endowment in rats exposed to maternal protein restriction. AB - A reduced nephron complement at birth renders the kidney susceptible to renal disease in adulthood. Retinoic acid (RA; the active metabolite of vitamin A) is linked to nephrogenesis in vitro and in vivo. The aim of this study was to determine the effect of administration of retinoic acid in midgestation in rats on nephron endowment in offspring exposed to maternal protein restriction. Rats were fed either a normal-protein diet (NPD) or a low-protein diet (LPD) during pregnancy and lactation. Half of the dams in the LPD group were injected intraperitoneally with retinoic acid (20 mg/kg) during gestation at embryonic day 11.5. At 4 weeks of age, the offspring were anesthetized and perfusion-fixed, and nephron number estimated using unbiased stereological techniques. Body weight and kidney volume was significantly reduced in all LPD offspring. There was a significant 29% reduction in nephron number in the LPD group compared with the NPD offspring, whereas the number of nephrons in kidneys from the LPD + RA offspring was not significantly different compared with controls. In conclusion, administration of a single bolus dose of retinoic acid during midgestation restored nephron endowment to normal in offspring exposed to maternal protein restriction. PMID- 17849155 TI - In pursuit of QALY weights for relatives: empirical estimates in relatives caring for older people. AB - This study estimates quality-adjusted life-year (QALY) weights for relatives caring for an older person. The data used are from the Swedish part of the EUROFAMCARE study. A new measure is introduced called the R-QALY weight, defined as the effect on a relative's QALY weight due to being a relative of a disabled or sick individual. R-QALY weights were created by comparing relatives' QALY weights with population-based QALY weights. They were also created by comparing with QALY weights reassessed for a hypothetical situation in which the older person needed no care. The results indicate that R-QALY weights are small when compared with population-based weights, but large when compared with QALY weights reassessed for the hypothetical situation. Moreover, R-QALY weights were affected by relatives' age, sex, and subjective perception of positive and negative aspects of the caregiving situation. These aspects should therefore be taken into account in health economics evaluations using a societal approach. PMID- 17849156 TI - Do all non-calcified echogenic renal lesions found on ultrasound need further evaluation with CT? AB - BACKGROUND: This is a study using Evidence Based Practice (EBP) technique to evaluate if non-calcified renal lesions detected with ultrasound, suspected to represent an angiomyolipoma (AML), need a CT to rule out a renal cell carcinoma (RCC). METHODS: The secondary and primary literature were searched for all relevant information. This was appraised for validity and strength. The results from the papers with the highest level of evidence were grouped together and analyzed. RESULTS: Three papers in the primary literature constituted the highest level of evidence. In total these three papers examined 220 lesions. The prevalence of AML was 45% in this sample. Overall, hyperechoic non-calcified renal lesions had a sensitivity of 0.99 (95% confidence interval (CI) 0.97-1.00), a specificity of 0.43 (95% CI 0.34-0.51), a positive predictive value (PPV) of 0.58 and a negative predictive value (NPV) of 0.98 for AMLs. 57.4% of RCCs were hyperechoic to renal parenchyma. Two of the studies found that posterior acoustic shadowing had a sensitivity of 0.34 (95% CI 0.40-0.56) and a specificity of 1.0 (95% CI 1.0-1.0) for AML. CONCLUSIONS: From the surprisingly limited evidence available in the literature, it must be concluded that all non-calcified echogenic renal lesions detected with ultrasound need a CT to rule out an RCC. PMID- 17849158 TI - Risk of seroma with simultaneous liposuction and abdominoplasty and the role of progressive tension sutures. AB - BACKGROUND: This study aimed to evaluate the true risk of seroma with simultaneous abdominoplasty and liposuction and to assess the role of progressive tension suture in preventing it. METHODS: A retrospective chart review of 235 consecutive abdominoplasties performed by a single surgeon was conducted. Matarasso classification was used, and 146 patients with type 4 abdominoplasty were selected. These patients were divided into two groups. The 96 patients in group A had no progressive tension sutures. This group was further subdivided into subgroup A1 (43 patients), which had abdominoplasty alone, and subgroup A2 (53 patients), which had abdominoplasty with liposuction. The 50 patients in group B had progressive tension sutures. This group was further subdivided into subgroup B1 (26 patients), which had abdominoplasty alone, and subgroup B2 (24 patients), which had abdominoplasty with liposuction. RESULTS: The two groups were similar in terms of body mass index, age, and smoking status. The incidence of seroma formation was 26% (n = 25) in group A, as compared with 4% (n = 2) in group B (p = 0.001). Group B showed 0% seroma formation when abdominoplasty alone was performed, as compared with 7.7% when liposuction was performed at the same time (p = 0.08, no statistical difference). Also, no statistical difference was seen when similar subgroups were compared in group A (p = 0.87). CONCLUSION: The findings of this retrospective study show that the application of progressive tension sutures in abdominoplasty significantly reduces the incidence of seroma, and that simultaneous abdominoplasty with liposuction does not contribute to this complication. PMID- 17849159 TI - Ecophysiological competence of Populus alba L., Fraxinus angustifolia Vahl., and Crataegus monogyna Jacq. used in plantations for the recovery of riparian vegetation. AB - In many semi-arid environments of Mediterranean ecosystems, white poplar (Populus alba L.) is the dominant riparian tree and has been used to recover degraded areas, together with other native species, such as ash (Fraxinus angustifolia Vahl.) and hawthorn (Crataegus monogyna Jacq.). We addressed three main objectives: (1) to gain an improved understanding of some specific relationships between environmental parameters and leaf-level physiological factors in these riparian forest species, (2) to compare the leaf-level physiology of these riparian species to each other, and (3) to compare leaf-level responses within native riparian plots to adjacent restoration plots, in order to evaluate the competence of the plants used for the recovery of those degraded areas. We found significant differences in physiological performance between mature and young white poplars in the natural stand and among planted species. The net assimilation and transpiration rates, diameter, and height of white poplar plants were superior to those of ash and hawthorn. Ash and hawthorn showed higher water use efficiency than white poplar. White poplar also showed higher levels of stomatal conductance, behaving as a fast-growing, water-consuming species with a more active gas exchange and ecophysiological competence than the other species used for restoration purposes. In the restoration zones, the planted white poplars had higher rates of net assimilation and water use efficiency than the mature trees in the natural stand. We propose the use of white poplar for the rapid restoration of riparian vegetation in semi-arid Mediterranean environments. Ash and hawthorn can also play a role as accompanying species for the purpose of biodiversity. PMID- 17849160 TI - Splenic trauma in Scotland: demographics and outcomes. AB - BACKGROUND: Splenic trauma is a common organ injury following blunt abdominal trauma. In order to establish the contemporary epidemiology of blunt splenic trauma in Scotland and to detect risk factors associated with patient outcomes, analysis of a multi-center database of trauma patients was performed. METHODS: The study used data from a prospectively collated multicenter trauma database containing the details of 52,215 trauma patients admitted to participating Scottish hospitals over an 11-year period. RESULTS: 672 (1.3%) patients (530 males, 142 females) with splenic trauma were identified; of them, 579 (86.2%) had blunt trauma and 93 (13.8%) had penetrating trauma. The mean age of patients with blunt splenic trauma was 35.7 years (33.8 years for males, 42.0 years for females). Increasing age and female sex was significantly associated with mortality. The most common mechanism for injury was road traffic accidents (71%). In the series, 93.8% of patients had concomitant injuries including head injuries (46.5%), thoracic injuries (37.7%) and liver injuries (30%). A total of 299 (51.6%) patients proceeded to laparotomy, and 256 (44.2%) patients required ICU support. The overall mortality was 33.5%, and the median Injury Severity Score was 48 in patients who died, compared to 22 in those who survived. Increased mortality was associated with concomitant aortic, cardiac, or abdominal injuries. A number of independent risk factors were associated with increased risk of mortality, including concomitant injuries, increased age, and increased Injury Severity Score. CONCLUSIONS: The incidence of splenic trauma is low, but it accounts for significant mortality. Outcome in the present study was worse in those with advanced age and associated injuries. PMID- 17849161 TI - Physiological and biochemical alterations in a diazotrophic cyanobacterium Anabaena cylindrica under NaCl stress. AB - Growth, morphological variation, and liquid chromatography-photodiode array detection-mass spectrometric analysis of pigments have been studied in a diazotrophic cyanobacterium Anabaena cylindrica in response to NaCl stress. The chlorophyll and cellular protein contents increased initially in response to 50 mM: NaCl. Further increment in NaCl concentration, however, resulted in a significant decrease in both chlorophyll and cellular protein. A. cylindrica cells subjected to NaCl stress also showed morphological variations by having alteration in their size and volume. A. cylindrica cells subjected to NaCl stress also exhibited altered plastoquinone and chlorophyll-a (chl a) levels in comparison to its NaCl-untreated counterpart. Furthermore, a relative increase in plastoquinone level and a subsequent decrease in chl a level were recorded in NaCl adapted cells of A. cylindrica in response to NaCl stress. These results suggest that owing to adaptation various morphological, physiological, and biochemical changes occur in the cyanobacterium A. cylindrica in response to NaCl stress. PMID- 17849162 TI - A novel bacteriocin-like substance produced by Enterococcus faecium 3587. AB - Secretion of a novel bacteriocin-like inhibitory substance from Enterococcus faecium 3587 is described herein for the first time. Whereas some bacteriocins receive their denomination based on the species or genus name of the producer microorganism, the newly discovered bacteriocin-like substance was named "enterocin 3587." The growth characteristics of the producer strain, as well as the type of production and the primary characteristic of the peptide, were investigated. It was found by sodium dodecyl sulfate-polyacrylamide gel electrophoresis that the molecule possesses a molecular weight <6.5 kDa; its secretion is growth-phase dependent; and it shows activities only against other closely related enterococci but not against other Gram-positive bacteria, such as L. innocua, S. aureus 209, and Lactobacillus delbrueckii B2, nor against some Gram-negative species, such as Escherichia coli HB101. PMID- 17849163 TI - Cloning and characterization of pBMB9741, a native plasmid of Bacillus thuringiensis subsp. kurstaki strain YBT-1520. AB - A native plasmid of Bacillus thuringiensis subsp. kurstaki strain YBT-1520 named pBMB9741 has been successfully cloned, sequenced, and characterized. Twelve open reading frames of at least 50 amino acids were identified. BLAST search indicated that three of them encode conserved proteins involved in conjugative mobilization, replication initiation, and transcription regulation. The orf6 located within a 2.2-kb minimal replication region was predicted to encode a replication protein. An homologous study of the orf6 product suggested that this plasmid might engage a rolling-circle replication mechanism. Unlike many other plasmids that adopt a rolling-circle model to replicate, pBMB9741 demonstrated strong segregation stability. When tested at 28 degrees C, 37 degrees C, and 42 degrees C, this plasmid maintained 100% stability in a variety of strains, including wild-type strains of B. thuringiensis and B. cereus, as well as plasmidless mutants of B. thuringiensis subsp. kurstaki and subsp. israelensis. PMID- 17849164 TI - Development of a bacterial surface display of hexahistidine peptide using CS3 pili for bioaccumulation of heavy metals. AB - A novel cell surface display system for metal uptake was developed using CS3 pili of enterotoxigenic Escherichia coli, which is a suitable system for display of heterologous peptides. The recombinant bacteria producing the hybrid pili containing the hexahistidine peptide accumulated high concentrations of Cd(2+) and Ni(2+) at 656.2 and 276.5 nmol per mg dry weight of bacterial cell, respectively. The recombinant bacteria may be useful in water and waste water treatment. PMID- 17849165 TI - Breast MRI wire-guided excisional biopsy: specimen size as compared to mammogram wire-guided excisional biopsy and implications for use. AB - BACKGROUND: Breast magnetic resonance imaging (MRI) has been implemented as a screening tool for early detection and as a diagnostic test in the management of breast cancer. Lesions identified by MRI but not amenable to conventional biopsy techniques require MRI wire-guided excisional biopsy (MRIbx). We hypothesized that more tissue would be resected with MRIbx compared to Mammobx. We also sought to evaluate factors that might predict the presence of breast cancer in patients undergoing MRIbx. METHODS: We reviewed consecutive cases of breast MRIbx from 2004 to 2006 performed by seven surgeons. MRI was performed in patients with either a synchronous breast cancer or significant risk factors. Lesions visualized only by MRI underwent diagnostic MRIbx. The control group was comprised of consecutive cases that underwent diagnostic Mammobx during the same time period. The volumes of tissue resected, overall and by pathologic outcome, were compared. RESULTS: Seventy-one patients, with a mean age of 48, underwent MRIbx. Eleven (15.5%) invasive breast cancers and eight cases (11.3%) of ductal carcinoma in situ (DCIS) were identified. The median volume of tissue resected was significantly greater than that in the Mammobx group (28.8 cm3 vs 21.1 cm3, respectively). DCIS-containing MRIbx specimens were significantly larger than benign or invasive cancer-containing specimens. There was no significant overall association between either the indication for MRIbx or the size of the MRI lesion and the frequency of cancer. CONCLUSIONS: In patients undergoing breast MRIbx, 27% were found to have DCIS or invasive breast cancer. MRIbx was associated with significantly larger specimen volumes than Mammobx. PMID- 17849166 TI - Systemic chemotherapy and two-stage hepatectomy for extensive bilateral colorectal liver metastases: perioperative safety and survival. AB - BACKGROUND: Two-stage hepatectomy has been proposed for patients with bilateral colorectal liver metastases (CLM). The aim of this study was to compare the outcome of patients with CLM treated with preoperative chemotherapy followed by one- or two-stage hepatectomy. METHODS: From a prospective database, 214 consecutive patients who received preoperative systemic chemotherapy (fluoropyrimidine with irinotecan or oxaliplatin) followed by planned one- or two stage hepatectomy were retrospectively analyzed (1998-2006). In patients undergoing two-stage procedures, minor hepatectomy (wedge or segmental resection[s]) was systematically performed before major (more than three segments), second-stage hepatectomy. Preoperative portal vein embolization (PVE) was performed if indicated. RESULTS: One- (group I) and two-stage (group II) hepatectomies were performed in 184 and 21 patients, respectively. Median number of metastases in groups I and II were two (range 1-20) and seven (range 2-20). All patients in group II had bilateral disease vs 39% in group I. Major hepatectomy was performed in all patients in group II and 79% in group I. PVE was performed in 18 group I and 12 group II patients without increase in morbidity. For group I, group II first stage, and group II second stage, respectively, morbidity (24%, 24%, 43%), median hospital stay (7 days, 6 days, 6.5 days) and 30 days postoperative mortality (2%, 0%, 0%) were not significantly different (P = NS). Median follow-up was 25 months; median survival has not been reached. One- and 3-year overall and disease-free survival rates from the time of hepatic resection were 95% and 75%, 63% and 39%, respectively in group I; 95% and 86%, 70% and 51%, respectively in group II (P = NS). CONCLUSIONS: Two-stage hepatectomy with preoperative chemotherapy results in comparable morbidity and survival rates as one-stage hepatectomy. This approach enables selection and treatment of patients with multiple, bilateral CLM who will benefit from aggressive surgery with good outcomes. PMID- 17849167 TI - Eosinophilic colitis. AB - Eosinophilic colitis is a rare chronic inflammatory bowel condition of unknown etiology. We report a case of cecal volvulus causing obstruction in a patient with eosinophilic colitis. A 48-year-old lady presented with abdominal pain, constipation, and abdominal distension. Clinically and radiologically, she was diagnosed to have cecal volvulus. Preoperative colonoscopic reduction failed. At laparotomy, a right hemicolectomy with primary anastomosis was undertaken. Histology of the resected specimen showed diffuse eosinophilic infiltration suggesting eosinophilic colitis. To the best of our knowledge, this association has been never reported. PMID- 17849168 TI - Effects of elevated glucose levels on interactions of cardiac fibroblasts with the extracellular matrix. AB - Exposure of fibroblasts to high glucose levels promotes a fibrotic response characterized by increased expression of extracellular matrix components including interstitial collagens. Little is known about the effects of glucose levels on other aspects of fibroblast function. Fibroblasts in the myocardium are surrounded by an extensive extracellular matrix composed predominantly of type I collagen. Interactions between fibroblasts and the myocardial extracellular matrix are thought to affect heart function by altering ventricular diastolic properties. The purpose of the present study was to determine the effects of elevated glucose levels on the interactions between heart fibroblasts and the collagenous extracellular matrix. Studies were performed to determine the effects of relative glucose levels on the ability of fibroblasts to migrate on and contract a three-dimensional collagenous substratum. These experiments illustrated that exposure of cardiac fibroblasts to high glucose levels (25 mM) resulted in decreased migratory activity of fibroblasts on a collagen matrix and decreased fibroblast proliferation. In addition, high glucose stimulated collagen and collagen-binding integrin expression and contraction of three-dimensional collagen gels by cardiac fibroblasts. These studies illustrate that altered glucose levels induce important changes in the interactions of cardiac fibroblasts with the collagenous extracellular matrix. PMID- 17849169 TI - A possible role for intracellular GSH in spontaneous reaction of a cysteine (T338C) engineered into the Cystic Fibrosis Transmembrane Conductance Regulator. AB - The conductance of oocytes expressing T338C CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) exhibits variable responses to dithiothreitol (DTT) and 2 mercaptoethanol (2-ME) that we proposed might be due to the extraction of copper from an adventitious binding site (Liu et al. J Biol Chem 281(12):8275-8285, 2006). In order to study the origins of variability in chemical reactivity of T338C CFTR channels, oocytes expressing T338C CFTR were exposed to BCNU (bischloroethylnitrosourea), an inhibitor of glutathione reductase. BCNU treatment caused a significant reduction of initial conductance and an increase in the response to 2-ME or DTT, suggesting a direct or indirect influence of intracellular glutathione (GSH), a major determinant of the disposition of intracellular copper. Single-channel recordings indicated that T338C CFTR channels not exposed to 2-ME or DTT exhibited multiple conductance levels not seen in T338A CFTR channels. Exposure to BCNU shifted the distribution of single channel current amplitudes towards lower values, whereas exposure to DTT favored higher amplitudes. These results suggest that the altered chemical state of T338C channels is associated with a decreased single-channel conductance and that intracellular factors (most likely GSH) may modulate the propensity of the channel to form these altered states. PMID- 17849170 TI - Dietary fat-gene interactions in cancer. AB - Epidemiologic studies have suggested for decades an association between dietary fat and cancer risk. A large body of work performed in tissue culture and xenograft models of cancer supports an important role of various types of fat in modulating the cancer phenotype. Yet, the molecular mechanisms underlining the effects of fat on cancer initiation and progression are largely unknown. The relationships between saturated fat, polyunsaturated fat, cholesterol or phytanic acid with cancer have been reviewed respectively. However, few have considered the relationship between all of these fats and cancer. The purpose of this review is to present a more cohesive view of dietary fat-gene interactions, and outline a working hypothesis of the intricate connection between fat, genes and cancer. PMID- 17849171 TI - Magnesium-calcium signalling in rat parotid acinar cells: effects of acetylcholine. AB - This study investigated the effects of extracellular Mg(2+) ([Mg(2+)](o)) on basal and acetylcholine (ACh)-evoked amylase secretion and intracellular free Ca(2+) ([Ca(2+)](i)) in rat parotid acinar cells. In a medium containing 1.1 mM [Mg(2+)](o), ACh evoked significant increases in amylase secretion and [Ca(2+)](i). Either low (0 mM) or elevated (5 and 10 mM) [Mg(2+)](o) attenuated ACh-evoked responses. In a nominally Ca(2+) free medium, elevated [Mg(2+)](o) attenuated basal and ACh-evoked amylase secretion and [Ca(2+)](i). In parotid acinar cells incubated with either 0, 1.1, 5 or 10 mM [Mg(2+)](o), ACh evoked a gradual decrease in [Mg(2+)](i). These results indicate that the ACh-evoked Mg(2+) efflux is an active process since Mg(2+) has to move against its gradient. Either lidocaine, amiloride, N-methyl-D: -glucamine, quinidine, dinitrophenol or bumetanide can elevate [Mg(2+)](i) above basal level. In the presence of these membrane transport inhibitors, ACh still evoked a decrease in [Mg(2+)](i) but the response was less pronounced with either [Na(+)](o) removal or in the presence of either amiloride or quinidine. These results indicate marked interactions between Ca(2+) and Mg(2+) signalling in parotid acinar cells and that ACh-evoked Mg(2+) transport was not dependent upon [Na(+)](o). PMID- 17849172 TI - Upregulation of lysyl oxidase and MMPs during cardiac remodeling in human dilated cardiomyopathy. AB - OBJECTIVE: Dilated cardiomyopathy (DCM) represents a large subset of patients with congestive heart failure (HF), and myocardial fibrosis has been shown to be associated with this process. Lysyl oxidase (LOX), a key enzyme, plays a potential role in the biogenesis of connective tissue matrices by catalyzing crosslinks in collagen and elastin. However, the mechanisms involved in the remodeling process during HF are not clearly understood. The present work was aimed to determine the changes in collagen phenotypes, MMPs, TIMPs, and LOX, in DCM and non-failing human hearts. Moreover, the role of TGFbeta in the induction of type III collagen in cardiac fibroblast is determined. METHOD: Protein and RNA expression were quantified by Western and RT-PCR analysis; collagen phenotypes were determined by SDS-PAGE. RESULTS: Our data demonstrated that in all DCM hearts, the collagen concentration was significantly elevated compared to that of the NF hearts associated with an increase in Type I (18%) and Type III (33%) collagen. The content of MMP-2 and MMP-9 were increased significantly in all DCM hearts compared to NF hearts. Transcriptional level of LOX, TIMP 1, and 2 were significantly upregulated in DCM hearts. In addition, a significant increase in the transcript levels of cytokines, notably IFN, IL-6, TNF-alpha, and TGF-beta superfamily was observed in all DCM hearts. Addition of TGFbeta to cardiac fibroblasts caused a dose dependent increase in type III collagen. CONCLUSION: Altogether, our data suggest an alteration of collagen, MMPs, various cytokines and particularly, LOX participates, in part, in the remodeling of the heart leading to cardiac dysfunction and HF. PMID- 17849173 TI - The function study on the interaction between Grb2 and AMPK. AB - Growth factor receptor-bound protein 2 (Grb2) is an extensively studied adaptor protein involved in cell signaling. Grb2 is a highly flexible protein composed of a single SH2 domain flanked by two SH3 domains. The evolutionarily conserved serine/threonine kinase, AMP-activated protein kinase (AMPK), functions as a cellular fuel gauge that regulates metabolic pathways in glucose and fatty acid metabolism and protein synthesis. AMPK regulates the activation of TSC2 by phosphorylating TSC2. Here we report for the first time on the interaction of Grb2 with AMPK. SH2 domain of Grb2 and KIS domain of AMPK are both required for the combination of Grb2 and AMPK. Furthermore, Grb2 function as a factor which mediates phosphorylation of AMPK at Thr172, and potentially involves in metabolism pathways and AMPK-TSC2-mTOR cell growth pathway through regulating the activation of AMPK. PMID- 17849174 TI - Notch activation promotes cell proliferation and the formation of neural stem cell-like colonies in human glioma cells. AB - Since Notch signaling plays a critical role in stem cells and oncogenesis, we hypothesized that Notch signaling might play roles in cancer stem cells and cancer cells with a stem cell phenotype. In this study, we accessed potential functions of the Notch pathway in the formation of cancer stem cells using human glioma. Using RT-PCR, we found that most human astrogliomas of different grades expressed moderate to high level of Notch receptors and ligands. mRNA of Hes5 but not Hes1, both of which are major downstream molecules of the Notch pathway, was also detected. In human glioma cell lines BT325, U251, SHG-44, and U87, mRNA encoding different types of Notch receptors were detected, but active form of Notch1 (NIC) was only detected in SHG-44 and U87 by Western blot. Interestingly, proliferation of these two glioma cell lines appeared faster than that of the other two lines in which NIC was not detected. We have over-expressed NIC of Notch1 in SHG-44 cells by constitutive transfection to evaluate the effects of Notch signaling on glioma cells. Our results showed that over-expression of NIC in SHG-44 cells promoted the growth and the colony-forming activity of SHG-44 cells. Interestingly, over-expression of NIC increased the formation neurosphere like colonies in the presence of growth factors. These colonies expressed nestin, and could be induced to cells expressing neuron-, astrocyte-, or oligodendrocyte specific markers, consistent with phenotypes of neural stem cells. These data suggest that Notch signaling promote the formation of cancer stem cell-like cells in human glioma. PMID- 17849175 TI - Fibrinogen induces endothelial cell permeability. AB - Many cardiovascular and cerebrovascular disorders are accompanied by an increased blood content of fibrinogen (Fg), a high molecular weight plasma adhesion protein. Fg is a biomarker of inflammation and its degradation products have been associated with microvascular leakage. We tested the hypothesis that at pathologically high levels, Fg increases endothelial cell (EC) permeability through extracellular signal regulated kinase (ERK) signaling and by inducing F actin formation. In cultured ECs, Fg binding to intercellular adhesion molecule-1 and to alpha(5)beta(1) integrin, caused phosphorylation of ERK. Subsequently, F actin formation increased and coincided with formation of gaps between ECs, which corresponded with increased permeability of ECs to albumin. Our data suggest that formation of F-actin and gaps may be the mechanism for increased albumin leakage through the EC monolayer. The present study indicates that elevated un-degraded Fg may be a factor causing microvascular permeability that typically accompanies cardiovascular and cerebrovascular disorders. PMID- 17849176 TI - Chemical groups that adhere to the surfaces of living malignant cells. AB - PURPOSE: We determined the adhesion of particles with phenyl, carboxylic acid (COOH), amine, dialkyl phosphonate, ester, and hydroxyl groups to malignant and nonmalignant cells, in order to better design drug delivery systems (DDS) for malignant cells. METHODS: Living mouse melanoma skin (B16F10) and noncancerous mouse fibroblast (L929) cells, and an Atomic Force Microscope were used to determine the adhesion strengths. RESULTS: The measurement of the particles against B16F10 cells showed that COOH had the highest average maximum adhesion force () and a large standard deviation (std), and phenyl had the lowest and a lower std. The high and std suggested that COOH was binding the strongest to malignant cells, and to groups overexpressed on malignant cells. In the case of L929 cells, of phenyl and COOH were higher and lower, respectively, than those of the B16F10 cells. Additionally, Phenyl and COOH gave a lower std than that for the B16F10 cells. These results suggest that the lower binding of COOH to the nonmalignant cells was due to the lower number of groups that were overexpressed in the malignant cells. CONCLUSIONS: Our results suggest that COOH is the best group for malignant cell targeting DDS systems. PMID- 17849177 TI - Influence of plasma cholesterol and triglyceride concentrations and eritoran (E5564) micelle size on its plasma pharmacokinetics and ex vivo activity following single intravenous bolus dose into healthy female rabbits. AB - PURPOSE: Eritoran (E5564) is a glycophospholipid that acts as a toll-like receptor 4 (TLR4) antagonist that is being tested as a treatment for severe sepsis and septic shock. In the blood, eritoran binds to plasma lipoproteins altering its pharmacokinetic and pharmacodynamic (PD) effects in vivo. The purpose of this study was to determine the influence of changes in plasma cholesterol and triglyceride concentrations on the plasma pharmacokinetics and ex vivo activity of eritoran following single intravenous bolus dosing of eritoran to healthy female rabbits fed either a regular chow diet or a cholesterol enriched diet. This was done with eritoran administered as stable micelle formulations of mean hydrodynamic diameters of 8 or 27 nm). METHODS: Female New Zealand White rabbits were fed a standard diet for 7 days and then randomly assigned either a regular chow diet [regular-diet (n = 9)] or a cholesterol enriched diet [cholesterol-diet (n = 12)] for an additional 7 days. Following feeding of these diets a single intravenous bolus dose of eritoran (0.5 mg/kg) formulated into either "small micelles" (8 nm in diameter) or "large micelles" (27 nm in diameter) was administered to regular-fed and cholesterol-fed rabbits. Serial blood samples were obtained prior to eritoran administration and at the following times post injection: 0.083 (5 min), 1, 2, 4, 8, 10, 24, 48 and 72 h. Plasma was analyzed for eritoran concentrations using LC/MS/MS. Total plasma cholesterol (TC) and triglyceride (TG) levels were quantified using enzymatic kits. Plasma eritoran pharmacokinetic (PK) parameters were estimated by non compartmental analysis using the WinNonlin nonlinear estimation program. To analyze PD activity, whole blood obtained at 0.083 (5 min), 2, 24, 48 and 72 h following eritoran administration was assessed for ex vivo activity by measuring the ability of 1 and 10 ng/ml LPS to elicit TNF-alpha release. RESULTS: Total plasma cholesterol and triglyceride levels were significantly higher in cholesterol-fed rabbits compared to the rabbits fed a regular chow diet. Diet had no effect on the estimated plasma PK parameters. However, PD activity of both small and large micelle eritoran as measured by an ex vivo challenge dose of 1 ng/ml LPS was reduced in blood of cholesterol-fed rabbits compared to normal-fed rabbits. Comparison of PK parameters for small and large micelles indicated that small micelles had increased AUC(0-72 h), decreased plasma clearance and increased initial concentration (measured at 5 min post administration) compared to the large micelle formulation. Consistent with this observation, eritoran formulated into small micelles had significantly greater ex vivo activity than large micelles and was independent of TC and TG concentrations. CONCLUSIONS: These findings suggest that plasma pharmacokinetics and activity of eritoran maybe influenced by eritoran micelle size and plasma TC and TG concentrations. PMID- 17849178 TI - Measuring self-efficacy in gambling: the Gambling Refusal Self-Efficacy Questionnaire. AB - This paper reports on the development and psychometric properties of a Gambling Refusal Self-Efficacy Questionnaire (GRSEQ). Two hundred and ninety-seven gamblers from both normal and clinical populations completed an initial set of 31 items of which 26 were selected for inclusion in the final version of the GRSEQ. A series of factor analyses showed four clear factors accounting for 84% of the variance. These factors can be summarised as situations and thoughts associated with gambling, the influence of drugs on gambling, positive emotions associated with gambling and negative emotions associated with gambling. The GRSEQ total score and factors scores showed high internal consistency (Cronbach's alpha ranging from 0.92 to 0.98). Participants experiencing problems with gambling scored significantly lower on the GRSEQ, and discriminant analyses showed that the scale is able to correctly classify the non-problem (i.e., community and student samples) and problem gamblers (i.e., clinical sample). Furthermore, the GRSEQ showed significant negative relationships with other gambling-related variables (gambling urge and gambling-related cognitions) and negative mood states (depression, anxiety and stress) and was shown to be sensitive to change in treatment of pathological gambling. The results suggest that the GRSEQ is a useful measure of gambling refusal self-efficacy that is suitable for assessment of gamblers from both normal and clinical populations. PMID- 17849179 TI - Low temperature metal-enhanced fluorescence. AB - In this short letter, we describe the effects of low temperature on the Metal Enhanced Fluorescence (MEF) phenomenon. Fluorophores close to Silver Island Films (SiFs) show on average two- to ten-fold enhancements in their fluorescence signatures at room temperature. However, at 77 K, we have observed that MEF is even more pronounced as compared to an identical glass control sample. We also demonstrate that the further enhancements in MEF occur at low temperature over a range of visible wavelengths for different fluorophores, for both SiFs and 20 nm surface deposited gold colloids. PMID- 17849180 TI - Fluorescence quenching and time-resolved fluorescence studies of alpha mannosidase from Aspergillus fischeri (NCIM 508). AB - Apart from the vital role in glycoprotein biosynthesis and degradation, alpha mannosidase is currently an important therapeutic target for the development of anticancer agents. Fluorescence quenching and time-resolved fluorescence of alpha mannosidase, a multitryptophan protein from Aspergillus fischeri were carried out to investigate the tryptophan environment. The tryptophans were found to be differentially exposed to the solvent and were not fully accessible to the neutral quencher indicating heterogeneity in the environment. Quenching of the fluorescence by acrylamide was collisional. Surface tryptophans were found to have predominantly positively charged amino acids around them and differentially accessible to the ionic quenchers. Denaturation led to more exposure of tryptophans to the solvent and consequently in the significant increase in quenching with all the quenchers. The native enzyme showed two different lifetimes, tau (1) (1.51 ns) and tau (2) (5.99 ns). The average lifetime of the native protein (tau) (3.187 ns) was not affected much after denaturation (tau) (3.219 ns), while average lifetime of the quenched protein samples was drastically reduced (1.995 ns for acrylamide and 1.537 ns for iodide). This is an attempt towards the conformational studies of alpha-mannosidase. PMID- 17849181 TI - Systemic administration of olygodeoxynucleotides with CpG motifs at priming phase reduces local Th2 response and late allergic rhinitis in BALB/c mice. AB - Oligodeoxynucleotides (ODN) with CpG motifs (CpG ODN) induce T helper (Th)1-type reaction. We aimed to evaluate the therapeutic effect of CpG ODN in the development of late allergic rhinitis induced by ovalbumin (OVA), which is one of Th2 diseaes, in BALB/c mice. Effects of a single dose of synthetic CpG-ODN (50 microg) intraperitoneally (i.p.) at the priming phase (on day 0) by OVA on the development of late eosinophilic rhinitis at respiratory areas were compared to the control mice treated with its vehicle (ODN without CpG motifs; 50 microg). Animals were again sensitized by OVA (on day 10) i.p., and 4 days after second sensitization animals were challenged by OVA intranasally (on day 14). Four days after challenge, eosinophilic reactions, nasal lesions and local cytokine values were examined. Compared to the control group, the CpG ODN-administration increased production of OVA-specific Th1 cytokine (interferon-gamma) and decreased productions of ovalubmin-specific Th2 cytokines [interleukin (IL)-5 and IL-13] in nasal cavity fluids, supernatants of splenocytes and/or sera. Also, eosinophilia and increased total IgE values were decreased in mice treated with the CpG ODN compared to the control group. Moreover, nasal lesions with infiltration of eosinophils were prominently reduced by the CpG ODN-treatment compared to the control mice. The present study suggests that the systemic administration of CpG ODN at the priming phase may reduce local OVA-specific Th2 responses, resulting in decreased nasal pathology in the late allergic eosinophilic rhinitis. PMID- 17849182 TI - Race and ethnicity differences in reporting of depressive symptoms. AB - Our study explored race and ethnicity differences in reporting of symptoms to physicians and other practitioners among respondents to the 1999 National Health Interview Survey who screened positive for depression. Respondents were asked if they had told a doctor or another practitioner (nurse, social worker, psychologist, clergy, other) about their problems. Whites and Hispanics were significantly more likely to communicate with a physician or other practitioner than were African Americans, even with personal characteristics held constant. Practitioners should actively elicit descriptions of feelings and mood, especially with African Americans, and be prepared to treat or refer patients appropriately. PMID- 17849183 TI - Reliability and validity of the Chinese version of the Social Anxiety Scale for Adolescents. AB - This study evaluated the psychometric properties of the Chinese version of the Social Anxiety Scale for Adolescents (SAS-A) in a sample of 296 adolescents (49% boys) in Grades 7, 8, 9, 10, and 12 with a mean age of 15.52 years. Confirmatory factor analysis replicated the three-factor structure of the SAS-A in the Chinese sample: Fear of Negative Evaluation (FNE), Social Avoidance and Distress in New Situations (SAD-New), and Social Avoidance and Distress-General (SAD-General). Internal consistency and test-retest reliability were appropriate. The results also revealed a clear and predictable pattern of relationships between the SAS-A and the Questionnaire about Interpersonal Difficulties for Adolescents and the International Personality Item Pool. Chinese boys reported greater SAD-General than Chinese girls, and this difference increased with grade. The SAS-A scores were compared to previously collected data from the USA and Spain, revealing that Chinese adolescents scored significantly higher in social anxiety than American and Spanish adolescents. PMID- 17849184 TI - Benign proliferative epithelial disorders of the breast: a review of the epidemiologic evidence. PMID- 17849185 TI - A numerical model of skin electropermeabilization based on in vivo experiments. AB - As an alternative to viral methods that are controversial because of their safety issues, chemical and physical methods have been developed to enhance gene expression in tissues. Reversible increase of the cell membrane permeability caused by the electric field--electroporation--is currently one of the most efficient and simple non-viral methods of gene transfer. We performed a series of in vivo experiments, delivering plasmids to rat skin using external plate electrodes. The experiments showed that skin layers below stratum corneum can be permeabilized in this way. In order to study the course of skin tissue permeabilization by means of electric pulses, a numerical model using the finite element method was made. The model is based on the tissue-electrode geometry and electric pulses used in our in vivo experiments. We took into account the layered structure of skin and changes of its bulk electrical properties during electroporation, as observed in the in vivo experiments. We were using tissue conductivity values found in literature and experimentally determined electric field threshold values needed for tissue permeabilization. The results obtained with the model are in good agreement with the in vivo results of gene transfection in rat skin. With the model presented we used the available data to explain the mechanism of the tissue electropermeabilization propagation beyond the initial conditions dictated by the tissue initial conductivities, thus contributing to a more in-depth understanding of this process. Such a model can be used to optimize and develop electrodes and pulse parameters. PMID- 17849186 TI - Modified fabrication process of protein chips using a short-chain self-assembled monolayer. AB - In previous work a short chain SAM, 4,4-Dithiodibutyric Acid (DTBA) was found to be a thin monolayer in protein chips. However, obtaining uniform fluorescent intensity remains difficult because water-soluble carbodiimides (EDC) in an aqueous system cause the hydrolysis of N-hydroxysuccinimide ester (NHS esters). The hydrolysis of NHS esters reduces coupling yields and therefore reduces the fluorescent intensity of protein chips. The NHS can increase the stability of active intermediate resulting from the reaction of EDC and NHS, but the ratio of the concentration of EDC to that of NHS strongly affects this stability. The effects of the solvents used in the washing step are studied to solve this problem. The results reveal that PBST (PBS + 5% Tween20) is more effective in reducing the hydrolysis of NHS esters than deionized water. Additionally, the effects of 3:1 and 5:2 EDC/NHS ratios on the chips are examined. The 3:1 EDC/NHS ratio yields a higher fluorescent intensity than the 5:2 ratio. The effects on the chips of dissolving EDC in DI water, DI water + 0.1 M MES and alcohol are also investigated. The results show that alcohol provides higher fluorescent intensity than other solvents and the reaction time of 4 h yields a high fluorescent intensity with 3:1 EDC/NHS ratio. A modified fabrication process of protein chips using 4,4-DTBA is developed. In this work, 160 mM 4,4-DTBA is used as a self-assembled monolayer in the fabrication of protein chips. Experiments to characterize 4,4-DTBA are performed by contact angle goniometry and Fourier transform infrared spectroscopy (FTIR). Furthermore, the immobilized protein A FITC (fluorescein isothiocyanate) is adopted in fluorescent assays. PMID- 17849187 TI - In situ micropatterning technique by cell crushing for co-cultures inside microfluidic biochips. AB - To perform dynamic cell co-culture on micropatterned areas, we have developed a new type of "on chip and in situ" micropatterning technique. The microchip is composed of a 200 microm thick PDMS (polydimethylsiloxane) chamber at the top of which are located 100 mum thick microstamps. The PDMS chamber is bonded to a glass slide. After sterilization and cell adhesion processes, a controlled force is applied on the top of the PDMS chamber. Mechanically, the microstamps come into contact of the cells. Due to the applied force, the cells located under the microstamps are crushed. Then, a microfluidic perfusion is applied to rinse the microchip and remove the detached cells. To demonstrate the potential of this technique, it was applied successfully to mouse fibroblasts (Swiss 3T3) and liver hepatocarcinoma (HepG2/C3a) cell lines. Micropatterned areas were arrays of octagons of 150, 300 and 500 microm mean diameter. The force was applied during 30 to 60s depending on the cell types. After cell crushing, when perfusion was applied, the cells could successfully grow over the patterned areas. Cultures were successfully performed during 72 h of perfusion. In addition, monolayers of HepG2/C3a were micropatterned and then co cultured with mouse fibroblasts. Numerical simulations have demonstrated that the presence of the microstamps at the top of the PDMS chamber create non uniform flow and shear stress applied on the cells. Once fabricated, the main advantage of this technique is the possibility to use the same microchip several times for cell micropatterning and microfluidic co-cultures. This protocol avoids complex and numerous microfabrication steps that are usually required for micropatterning and microfluidic cell culture in the same time. PMID- 17849188 TI - Associations in sense of coherence and depression in caregivers of stroke survivors across 2 years. AB - The objective of this longitudinal study was to detect the relationship between the sense of coherence (SOC), which is an adaptive coping response, and depression in informal caregivers of stroke survivors across 2 years. One-hundred fifteen veterans, who were hospitalized after experiencing an acute stroke, and their informal caregivers were enrolled prior to discharge. Data were collected via face-to-face in-home interviews at 1, 6, 12, 18, and 24 months after discharge. A linear mixed model was fitted to estimate the effects of the time dependent covariates (SOC) while considering the dependence of outcome measures at repeated times. Based on the linear mixed model, caregivers with a stronger SOC were associated with lower levels of caregiver depression across 2 years following a stroke (p < 0.0001). SOC seems to be an important aspect of a caregiver's capacity to cope after tending to the needs of a stroke patient. PMID- 17849189 TI - RAPID automatized naming (RAN); neurological substrates of dyslexia. PMID- 17849190 TI - Samuel Torrey Orton Award to Martha Bridge Denckla: citation acceptance speech of Samuel Torrey Orton Award Martha Bridge Denckla. PMID- 17849191 TI - Dyslexia--a molecular disorder of neuronal migration: the 2004 Norman Geschwind Memorial Lecture. AB - For 25 years now, there has been a serious attempt to get at the fundamental cause(s) of dyslexia in our laboratory. A great deal of research has been carried out on the psychological and brain underpinnings of the linguistic dysfunctions seen in dyslexia, but attempts to get at its cause have been limited. Initially, observations were made on the brains of persons with dyslexia who had died and their brains donated for research. These observations were modeled in animal models in order to better understand the full extent of anatomical and developmental brain characteristics. More recently, models have begun to employ genetic manipulations in order to close the gap between genes, brain, and behavior. In this article based on a lecture given in memory of Dr. Norman Geschwind to the International Dyslexia Association assembly in Philadelphia in 2004, I outline the history of the research leading up to the most recent findings. These findings consist of experiments using methods that interfere with the function of DNA, using as constructs genes that have been implicated in dyslexia, which cause developmental problems of neuronal migration in rats, secondary brain changes in response to the migration problems, and abnormal processing of sounds. PMID- 17849192 TI - Language development and literacy skills in late-talking toddlers with and without familial risk for dyslexia. AB - The relationship between late-talkers' language development and reading and spelling outcomes was examined in children with and without familial risk for dyslexia. The late-talking subgroups were defined using parent- and test-based assessments of receptive and expressive vocabulary and grammar at 2 and 2.5 years as intake criteria. The language skills of late talkers and the remainders of these two groups were assessed at 3.5, 5, and 5.5 years. Reading/spelling outcomes were compared at the end of the second grade. Late-talking toddlers of the at-risk group who had both poor receptive and expressive skills performed less well than all other groups on language measurements at 5.5 years. In contrast, the control group's late talkers with an expressive delay reached the language level of their age-mates already by 3.5 years, and maintained their age appropriate position two years later. The most significant differences in the reading skills were found between the at-risk children with receptive and expressive delay and the remainder of the controls. Age-appropriate early language skills did not, however, ensure norm-level fluent reading in the at-risk group. The remainder of the at-risk group performed at a significantly lower level than did the remainder of the controls, both on the oral reading and spelling tasks. PMID- 17849193 TI - Predictive assessment of reading. AB - Study 1 retrospectively analyzed neuropsychological and psychoeducational tests given to N=220 first graders, with follow-up assessments in third and eighth grade. Four predictor constructs were derived: (1) Phonemic Awareness, (2) Picture Vocabulary, (3) Rapid Naming, and (4) Single Word Reading. Together, these accounted for 88%, 76%, 69%, and 69% of the variance, respectively, in first, third, and eighth grade Woodcock Johnson Broad Reading and eighth grade Gates-MacGinitie. When Single Word Reading was excluded from the predictors, the remaining predictors still accounted for 71%, 65%, 61%, and 65% of variance in the respective outcomes. Secondary analyses of risk of low outcome showed sensitivities/specificities of 93.0/91.0, and 86.4/84.9, respectively, for predicting which students would be in the bottom 15% and 30% of actual first grade WJBR. Sensitivities/specificities were 84.8/83.3 and 80.2/81.3, respectively, for predicting the bottom 15% and 30% of actual third grade WJBR outcomes; eighth grade outcomes had sensitivities/specificities of 80.0/80.0 and 85.7/83.1, respectively, for the bottom 15% and 30% of actual eighth grade WJBR scores. Study 2 cross-validated the concurrent predictive validities in an N=500 geographically diverse sample of late kindergartners through third graders, whose ethnic and racial composition closely approximated the national early elementary school population. New tests of the same four predictor domains were used, together taking only 15 minutes to administer by teachers; the new Woodcock Johnson III Broad Reading standard score was the concurrent criterion, whose testers were blind to the predictor results. This cross-validation showed 86% of the variance accounted for, using the same regression weights as used in Study 1. With these weights, sensitivity/specificity values for the 15% and 30% thresholds were, respectively, 91.3/88.0 and 94.1/89.1. These validities and accuracies are stronger than others reported for similar intervals in the literature. PMID- 17849194 TI - Neuropsychological intervention in kindergarten children with subtyped risks of reading retardation. AB - Kindergarten children at risk of developing language problems were administered the Florida Kindergarten Screening Battery. A principal components analysis revealed a verbal and a visual-spatial component and subsequent discriminant function analyses a high verbal/low visual-spatial group (LAL: Latent L) and a high visual-spatial/low verbal group (LAP: Latent P). LAL- and LAP-children were considered at risk for developing an L- or P-type of dyslexia, respectively. As is common practice with children suffering from manifest L- or P- dyslexia, the LAL- and LAP-kindergartners received right and left hemisphere stimulation, respectively. The outcomes were compared with those of bilateral hemispheric stimulation and no intervention. Reading tests were administered in primary school Grades 1 and 5/6; teachers' evaluation of reading took place in Grade 5/6. Overall, the LAL- and LAP- groups showed significant backwardness in word and text reading, both at early and late primary school. Types of intervention made a difference though: not significantly backward in early word, late word, and late text reading were the LAL-children who had received right hemisphere stimulation. Nonintervened LAP-children did not show significant backwardness in early word reading and late text reading, nor did LAP-children who had received left hemisphere or bilateral stimulation. Early text reading was not affected by any treatment. Teacher's evaluations were in support of these findings. PMID- 17849195 TI - Benefits of computer-presented speed training for poor readers. AB - The effects of computer-presented automatization exercises in a group of 14 poor readers were assessed in comparison to a matched control group of 14 poor readers that received computer-presented exercises aimed at the use of context for word identification and comprehension. Training took place three sessions a week for 15 minutes per session and lasted about two months in each group. Results showed that the automatization or "speed" group progressed more than the context group in word and text reading efficiency, and the effect transferred to more complex word types than the CVC word type that was presented in the exercises. Both groups progressed to the same extent in accuracy, but the speed group made more progress in speed. No effects were found for reading comprehension. The findings make clear that computer-supported automatization exercises can be effective in reducing reading problems of poor readers in a short period of time. Implications for practice are discussed. PMID- 17849196 TI - Teachers' literacy-related knowledge and self-perceptions in relation to preparation and experience. AB - After rating their own literacy-related knowledge in three areas (knowledge about reading/reading development, phonemic awareness/phonics, and morpheme awareness/structural analysis), graduate teacher-education students completed five tasks intended to measure their actual disciplinary knowledge in these areas. Teachers with high levels of prior background (i.e., course preparation and experience) rated themselves as significantly more knowledgeable than did low background teachers in all areas; high-background participants also significantly outperformed low-background participants on all tasks. However, even high background teachers scored well below ceiling on the tasks. Regression analyses indicated that teachers' self-perceptions and knowledge were positively influenced by both level of preparation and teaching experience, although the influences on teachers' knowledge differed by task. Teachers had some accurate perceptions of their own knowledge, especially in the area of phonics. Results suggest that differentiating levels of preparation may be useful in studying teacher knowledge, and also support the notion of a substantial gap between research on reading and teacher preparation in reading. PMID- 17849198 TI - Samuel Torrey Orton award to Margaret J. Snowling. Acceptance speech of Samuel Torrey Orton award. PMID- 17849199 TI - Genes, environment, and dyslexia. The 2005 Norman Geschwind Memorial Lecture. AB - This article presents an overview of some methods and results from our continuing studies of genetic and environmental influences on dyslexia, and on individual differences across the normal range that have been conducted over the past 25 years in the Colorado Learning Disabilities Research Center (CLDRC) and in related projects. CLDRC investigators compare the similarities of identical twin pairs who share all their genes and fraternal twins who share half their segregating genes to assess the balance of genetic, shared family environment, and nonshared environment influences on dyslexia and on individual differences across the normal range. We have learned that among the children we have studied in Colorado, group deficits in reading (dyslexia) and individual differences in reading across the normal range are primarily due to genetic influences, and these genetic influences are often shared with some of the same genetic influences on deficits and individual differences in language and ADHD. We have also learned from our molecular-genetic linkage studies that there are regions on several chromosomes likely to contain genes that influence dyslexia. Several specific genes within these regions have been tentatively identified through molecular-genetic association analyses, but much more research is needed to understand the pathways among specific genes, regions of noncoding DNA that regulate the activity of those genes, the brain, and dyslexia. I conclude with a discussion of our research on individual differences in early reading development, on the role of early learning constraints in dyslexia, and on how genetic influences are expressed through their interaction and correlation with the environment. PMID- 17849200 TI - Phonological processing and emergent literacy in Spanish-speaking preschool children. AB - Phonological awareness (PA), phonological memory (PM), and phonological access to lexical storage (also known as RAN), play important roles in acquiring literacy. We examined the convergent, discriminant, and predictive validity of these phonological processing abilities (PPAs) in 147 3-, 4-, and 5-year-old children whose native language was Spanish. Confirmatory factor analysis (CFA) supported the validity of each PPA as separate from general cognitive ability and separate from each other. Moreover, structural equation modeling found RAN uniquely associated with knowledge of Spanish letter names and Spanish letter sounds. PA was found the best predictor of children's ability to distinguish alphabetic text from nonalphabetic text. Finally, general cognitive ability was only indirectly associated with emergent literacy skills via PPAs. These results highlight the importance of PPAs in the early literacy development of native Spanish speaking preschool children. PMID- 17849201 TI - Spelling consistency affects reading in young Dutch readers with and without dyslexia. AB - Lexical-decision studies with experienced English and French readers have shown that visual-word identification is not only affected by pronunciation inconsistency of a word (i.e., multiple ways to pronounce a spelling body), but also by spelling inconsistency (i.e., multiple ways to spell a pronunciation rime). The aim of this study was to compare the reading behavior of young Dutch readers with dyslexia to the behavior of readers without dyslexia. All students participated in a lexical-decision task in which we presented pronunciation consistent words and pseudowords. Half of the pronunciation-consistent stimuli were spelling consistent and the other half were spelling inconsistent. All three reader groups, that is, students with dyslexia, age-match students, and reading match students, read spelling-consistent words faster than spelling-inconsistent words. Overall reading speed of students with dyslexia was similar to that of reading-match students, and was substantially slower than that of age-match students. The results suggest that reading in students with or without dyslexia is similarly affected by spelling inconsistency. Subtle qualitative differences emerged, however, with respect to pseudoword identification. The conclusion was that the findings were best interpreted in terms of a recurrent-feedback model. PMID- 17849202 TI - Spelling pronunciation and visual preview both facilitate learning to spell irregular words. AB - Spelling pronunciations are hypothesized to be helpful in building up relatively stable phonologically underpinned orthographic representations, particularly for learning words with irregular phoneme-grapheme correspondences. In a four-week computer-based training, the efficacy of spelling pronunciations and previewing the spelling patterns on learning to spell loan words in Dutch, originating from French and English, was examined in skilled and less skilled spellers with varying ages. Reading skills were taken into account. Overall, compared to normal pronunciation, spelling pronunciation facilitated the learning of the correct spelling of irregular words, but it appeared to be no more effective than previewing. Differences between training conditions appeared to fade with older spellers. Less skilled young spellers seemed to profit more from visual examination of the word as compared to practice with spelling pronunciations. The findings appear to indicate that spelling pronunciation and allowing a preview can both be effective ways to learn correct spellings of orthographically unpredictable words, irrespective of age or spelling ability. PMID- 17849203 TI - Spelling transparency and its impact on dyslexic and unimpaired children's memory for words. AB - The phonologically transparent Persian orthography is normally transcribed with two distinct spellings; words spelled with vowels (letters) transcribed as a fixed part of the spelling (transparent) and words spelled with vowels (diacritics) omitted (opaque). Three groups of Persian readers, namely developmental dyslexics (n=29, mean age=9.4, SD=1.4), unimpaired readers matched on age (n=49, mean age=9, SD=1.3), and reading age (n=23, mean age=7.2, SD=0.4) with the dyslexics performed on a short-term memory verbal test. The time taken to read aloud lists of words with opaque and transparent spellings, the errors made on reading the words in each list, and the number of correctly recalled words in each list was subjected to statistical analysis. The results showed that transparent words as a whole were read more accurately than opaque words. However, recall of words was best for opaque words for the older group of unimpaired readers compared to the transparent words, while the opposite was true for dyslexics and unimpaired reading age matched participants. The implications of these results are discussed. PMID- 17849204 TI - Rapid visual processing by college students in reading irregular words and phonologically regular pseudowords presented singly and in contiguity. AB - Using normal adult readers, this study examined the relative involvement of magnocellular and parvocellular processes in reading English phonologically regular pseudowords and irregular words presented in isolation and in contiguity from left to right. The data showed that a low temporal frequency visual measure that implied more parvocellular involvement was active in processing irregular words presented singly and pseudowords presented in contiguity. However, the results failed to show the involvement of the magnocellular pathway (as implicated by low spatial and/or high temporal frequency visual measures) in reading words presented in contiguity from left to right. The discrepancy was discussed in terms of the sensitivity of the tasks used in testing the two pathways. PMID- 17849205 TI - Reading, arithmetic, and task orientation--how are they related? AB - A sample of 60 children in Grade 3 was followed over one year. In the first year, an extensive battery of assessments was used including aspects of reading, arithmetic, and working memory. Teachers rated the children on 7-point scales on various motivational dimensions summarized to a total score tentatively called task orientation. In the follow-up assessment one year later, the testing and teacher ratings were repeated. The cross-sectional correlations between reading, arithmetic, and task orientation were all high (about +.70). The high correlation between reading and arithmetic decreased significantly when task orientation was partialed out, and it was further reduced when working memory as assessed by backward digit span was added to the controlling factors. Also, teacher ratings of cognitive ability and language development accounted for some of the common variance between reading and arithmetic. The correlation between task orientation and school achievement cannot be causally interpreted in cross-sectional designs. Some support for a "causal" hypothesis, however, was obtained in crosslagged correlation analyses indicating that task orientation in Grade 3 may have a causal impact on the level of performance in reading, and in arithmetic in Grade 4. Most likely, however, there is also a reciprocal relationship. PMID- 17849207 TI - Cultural and linguistic influence on brain organization for language and possible consequences for dyslexia: a review. AB - Current neuroimaging and neurophysiologic techniques have substantially increased our possibilities to study processes related to various language functions in the intact human brain. Learning to read and write influences the functional organization of the brain. What is universal and what is specific in the languages of the world are important issues. Most studies on healthy bilinguals indicate that essentially the same neural mechanisms are used for first and second languages, albeit with some linguistic and cultural influences related to speech and writing systems, particularly between alphabetical and nonalphabetical languages. Proficiency, age of acquisition, and amount of exposure can affect the cerebral representations of the languages. Accumulating data support the important role of working memory for acquiring high proficiency in the reading of native and second languages. It is proposed that longitudinal studies on second language acquisition are essential and that the specific problems related to second language learning in dyslexic children should have high priority. PMID- 17849208 TI - Reading fluency: the whole is more than the parts. AB - This study examined the relative contributions of phonological awareness, orthographic pattern recognition, and rapid letter naming to fluent word and connected-text reading within a dyslexic sample of 123 children in second and third grades. Participants were assessed on a variety of fluency measures and reading subskills. Correlations and hierarchical multiple regression analyses were carried out to explore these relationships. The results demonstrate that phonological awareness, rapid letter naming, and orthographic pattern recognition contribute to word-reading skills. Furthermore, rapid naming, orthographic pattern recognition, and word reading fluency moderately predict different dimensions of connected-text reading (i.e., rate, accuracy, and comprehension) whereas phonological awareness contributes only to the comprehension dimension of connected-text reading. The findings support the multidimensional nature of fluency in which the whole is more than its parts. PMID- 17849209 TI - Testing the double-deficit hypothesis in an adult sample. AB - The double-deficit hypothesis of dyslexia posits that reading deficits are more severe in individuals with weaknesses in phonological awareness and rapid naming than in individuals with deficits in only one of these reading composite skills. In this study, the hypothesis was tested in an adult sample as a model of reading achievement. Participants were parents of children referred for evaluation of reading difficulties. Approximately half of all participants reported difficulty learning to read in childhood and a small subset demonstrated ongoing weaknesses in reading. Structural equation modeling results suggest that the double-deficit hypothesis is an accurate model for understanding adult reading achievement. Better reading achievement was associated with better phonological awareness and faster rapid automatized naming in adults. Posthoc analyses indicated that individuals with double deficits had significantly lower reading achievement than individuals with single deficits or no deficits. PMID- 17849210 TI - Processing of derived forms in high-functioning dyslexics. AB - We report on an experiment designed to evaluate processing of derived forms in high-functioning dyslexics, defined as university students with a history of reading difficulties who have age-appropriate reading comprehension skills. We compared high-functioning dyslexics with a group of normal adult readers in their performance on a lexical decision task with derived items (such as cloudy and ably) and pseudo-derived items (such as belly and gravy). Some items contained an orthographic change (such as able-ably and gravy) and others did not (such as cloud - cloudy). The results indicated that although control participants' response times varied systematically as a function of morphological complexity, those of high-functioning dyslexics did not. Further, there was some evidence of a relationship between derivational processing and reading. It seems that high functioning dyslexics have persistent difficulties in processing one particular aspect of morphology; that of derived forms. PMID- 17849211 TI - Native language predictors of foreign language proficiency and foreign language aptitude. AB - Fifty-four students were tested at specific time intervals over 10 years to determine best native language (NL) predictors of oral and written foreign language (FL) proficiency and FL aptitude. All participants completed two years of Spanish, French, or German. Each was administered measures of NL literacy, oral language, and cognitive ability in elementary school. A measure of FL aptitude was administered at the beginning of ninth grade and FL proficiency was evaluated at the end of the 10th grade. Among the variables, NL literacy measures were the best predictors of FL proficiency, and NL achievement and general (verbal) intelligence were strong predictors of FL aptitude. Results suggest that indices of NL literacy as early as first grade are related to FL proficiency and FL aptitude nine and 10 years later. Findings provide strong support for connections between L1 and L2 skills, and for speculation that "lower level" skills in phonological processing are important for written language development and oral proficiency in a FL. PMID- 17849212 TI - Weak and strong novice readers of English as a foreign language: effects of first language and socioeconomic status. AB - This study examined individual differences among beginning readers of English as a foreign language (EFL). The study concentrated on the effects of underlying first language (L1) knowledge as well as EFL letter and vocabulary knowledge. Phonological and morphological awareness, spelling, vocabulary knowledge, and word reading in Hebrew L1, in addition to knowledge of EFL letters and EFL vocabulary, were measured. The study also investigated the effect of socioeconomic background (SES) on beginning EFL readers. Participants included 145 fourth graders from three schools representing two socioeconomic backgrounds in the north of Israel. The results indicate that knowledge of English letters played a more prominent role than knowledge of Hebrew L1 components in differentiating between strong and weak EFL readers. The Linguistic Coding Differences Hypothesis was supported by L1 phonological awareness, word reading, and vocabulary knowledge appearing as part of discriminating functions. The presence of English vocabulary knowledge as part of the discriminant functions provides support for English word reading being more than just a decoding task for EFL beginner readers. Socioeconomic status differentiated the groups for EFL word recognition but not for EFL reading comprehension. PMID- 17849214 TI - Reading development subtypes and their early characteristics. AB - The present findings are drawn from the Jyvaskyla Longitudinal Study of Dyslexia (JLD), in which approximately 100 children with familial risk of dyslexia and 100 control children have been followed from birth. In this paper we report data on the reading development of the JLD children and their classmates, a total of 1,750 children from four measurement points during the first two school years. In the total sample, we examined whether heterogeneous developmental paths can be identified based on profiles of word recognition and reading comprehension. Secondly, we studied what kind of early language and literacy skill profiles and reading experiences characterize the children with differing reading development in the follow-up sample. The mixture modeling procedure resulted in five subtypes: (1) poor readers, (2) slow decoders, (3) poor comprehenders, (4) average readers, and (5) good readers. The children with familial risk for dyslexia performed on average at a lower level in all reading tasks than both their classmates and the controls, and they were overrepresented in slow decoders subtype. Differences between the subtypes were found in the early language and literacy skill development, as well as in the reading experiences of the reading subtypes. PMID- 17849215 TI - Screening of phonological awareness in the early elementary grades: an IRT approach. AB - The purpose of the present study was to explore the possibilities for the assessment of growth in phonological awareness of children in kindergarten and first grade. Phonological awareness was measured using four sets of items involving rhyming, phoneme identification, phoneme blending, and phoneme segmentation. The results of an exploratory factor analysis and analyses conducted within the framework of item response theory showed one latent ability to underlie the different sets of items, which nevertheless differed in difficulty. Analyses in terms of the children's ability further showed the phonological awareness measures to be sensitive to growth. The amount of information supplied by the different sets of items depended on the children's level of ability. The conclusion that it is possible to accurately monitor the development of children's phonological awareness in the early elementary grades appears to be justified, and this possibility opens up new perspectives for the early screening for reading problems and dyslexia. PMID- 17849216 TI - Speech development patterns and phonological awareness in preschool children. AB - To examine the association between speech production and early literacy skills, this study of 102 preschool children looked at phonological awareness in relation to whether children were delayed, typical, or advanced in their articulation of consonants. Using a developmental typology inspired by some of the literature on speech development (Kahn and Lewis, The Kahn-Lewis phonological analysis, 1986; Shriberg, Journal of Speech and Hearing Research 36(1):105-140, 1993a), we found that failure to master the early-8 consonants and a greater prevalence of certain types of production errors were associated with deficient phonological awareness. We also found that children who made no consonant errors had advanced phonological awareness relative to other children in the sample. In all cases, both productive speech patterns and speech errors were more closely linked with rhyme awareness than with phoneme awareness. The association between speech production and rhyme awareness may provide some new directions for the early preschool assessment of risk for reading problems. PMID- 17849217 TI - Component skills of text comprehension in less competent Chinese comprehenders. AB - The present study examined the role of verbal working memory (memory span and tongue-twister), two-character Chinese pseudoword reading (two tasks), rapid automatized naming (RAN) (letters and numbers), and phonological segmentation (deletion of rimes and onsets) in inferential text comprehension in Chinese in 31 less competent comprehenders compared with 37 reading comprehension control students and 23 chronological age controls. It was hypothesized that the target students would perform poorly on these cognitive and linguistic tasks as compared with their controls. Furthermore, verbal working memory and pseudoword reading would explain a considerable amount of individual variation in Chinese text comprehension. RAN would have a nonsignificant role in text comprehension. Structural equation analyses and hierarchical multiple regression analyses generally upheld these hypotheses. Our findings support current literature of the role of verbal working memory in reading comprehension found in English. The results, however, suggest differential role of the constructs and the tasks in reading comprehension and provide some answers for comprehension impairment in Chinese students. PMID- 17849218 TI - Cognitive brain potentials in kindergarten children with subtyped risks of reading retardation. AB - Cognition-related brain responses to meaningful and meaningless figures were registered in 5-year-old kindergarten children who either had been subtyped as being at-risk of developing an L- or P-type dyslexia (LAL versus LAP) or who were not at-risk. While identifying, naming, or categorizing pictures, event-related potentials (ERP) were registered. Three cognition-related components were found: the N460, the P780, and the Slow Wave (SW). LAP-children produced weak N460 activity across tasks, whereas LAL children, and to a lesser degree, non-risk children produced robust task-dependent activity. This finding may indicate that LAP-children lack semantic input while processing the figures. P780 latencies to frequently occurring figures were found hemisphere-dependent: LAP-children showed longer latencies in the right than in the left hemisphere, whereas the distribution was reversed in the LAL and non-risk children. It was also found that the right hemisphere is generally responsible for a lion's share of the processing of figures and therefore it seems that the right hemisphere of LAP children invests ample time in doing so. Whereas LAP-children showed largest SW amplitude differences between frequent and infrequent stimuli at posterior locations, LAL children did so at frontal locations. Assuming that the SW represents working-memory processes, it may be that working-memory in LAP children deals with figure-relevant visual-spatial information and with figure derived concepts in LAL children. Overall, the findings suggest that LAL and LAP represent two different groups of kindergartners at risk of dyslexia and that these differences, to some degree, fit with the presumed etiology of L- and P type dyslexia. PMID- 17849219 TI - Analysis of expression profile of selected genes expressed during auxin-induced somatic embryogenesis in leaf base system of wheat (Triticum aestivum) and their possible interactions. AB - Somatic embryogenesis is a notable illustration of plant totipotency and involves reprogramming of development in somatic cells toward the embryogenic pathway. Auxins are key components as their exogenous application recuperates the embryogenic potential of the mitotically quiescent somatic cells. In order to unravel the molecular basis of somatic embryogenesis, cDNA library was made from the regeneration proficient wheat leaf base segments treated with auxin. In total, 1440 clones were sequenced and among these 1,196 good quality sequences were assembled into 270 contigs and 425 were singletons. By reverse northern analysis, a total of 57 clones were found to be upregulated during somatic embryogenesis, 64 during 2,4-D treatment, and 170 were common to 2,4-D treatment and somatic embryogenesis. A substantial number of genes involved in hormone response, signal transduction cascades, defense, anti-oxidation, programmed cell death/senescence and cell division were identified and characterized partially. Analysis of data of select genes suggests that the induction phase of somatic embryogenesis is accompanied by the expression of genes that may also be involved in zygotic embryogenesis. The developmental reprogramming process may in fact involve multiple cellular pathways and unfolding of as yet unknown molecular events. Thus, an interaction network draft using bioinformatics and system biology strategy was constructed. The outcome of a systematic and comprehensive analysis of somatic embryogenesis associated interactome in a monocot leaf base system is presented. PMID- 17849220 TI - Flavonoid profiling among wild type and related GM wheat varieties. AB - Pleiotropic effects are one of the main concerns regarding genetically modified organisms (GMOs). This includes unintended side effects of the transgene or its genome insertion site on the regulation of other endogenous genes, which could potentially cause the accumulation of different secondary metabolites that may have not only an impact on diet as repeatedly worried by the public but also on the environment. Regarding amount and possible environmental effects, flavonoids represent the most prominent group of secondary metabolites in wheat. Many flavonoids function as signalling or defence molecules. We used a robust and reproducible analytical method to compare the flavonoid content of genetically modified (GM) wheat (Triticum aestivum L., Gramineae) expressing genes that confer increased fungal resistance with their non-GM siblings. The transgenes provide either a broad-spectrum fungal defence (chitinase/glucanase from barley) or bunt-specific resistance by a viral gene (KP4). Significant differences in flavonoid composition were found between different wheat varieties whereas different lines of GM wheat with increased antifungal resistance showed only minor differences in their flavonoid composition relative to their non-GM siblings. In a field test, no significant differences were detectable between infected and non-infected wheat of the same variety regardless of the presence of the transgene. Our results are in agreement with the hypothesis that the transgenes we used to increase wheat defence to fungal pathogens do not interfere with the flavonoid biosynthesis pathway. More significantly, the genetic background resulting from conventional breeding has a direct impact on the biological composition of flavonoids, and thus possibly on the environment. PMID- 17849221 TI - A microcosm system and an analytical protocol to assess PAH degradation and metabolite formation in soils. AB - During bioremediation of polycyclic aromatic hydrocarbon (PAH)-polluted soils accumulation of polar metabolites resulting from the biological activity may occur. Since these polar metabolites are potentially more toxic than the parental products, a better understanding of the processes involved in the production and fate of these oxidation products in soil is needed. In the present work we describe the design and set-up of a static soil microcosm system and an analytical methodology for detection of PAHs and their oxidation products in soils. When applied to a soil contaminated with phenanthrene, as a model PAH, and 1-hydroxy-2-naphthoic acid, diphenic acid, and phthalic acid as putative metabolites, the extraction and fractionation procedures resulted in recoveries of 93%, 89%, 100%, and 89%, respectively. The application of the standardized system to study the biodegradation of phenanthrene in an agricultural soil with and without inoculation of the high molecular weight PAH-degrading strain Mycobacterium sp. AP1, demonstrates its suitability for determining the environmental fate of PAHs in polluted soils and for evaluating the effect of bioremediative treatments. In inoculated microcosms 35% of the added phenanthrene was depleted, 19% being recovered as CO(2) and 3% as diphenic acid. The latter, together with other two unidentified metabolites, accumulated in soil. PMID- 17849222 TI - Human osteoblast cell spreading and vinculin expression upon biomaterial surfaces. AB - Any biomaterial implanted within the human body is influenced by the interactions that take place between its surface and the surrounding biological milieu. These interactions are known to influence the tissue interface dynamic, and thus act to emphasize the need to study cell-surface interactions as part of any biomaterial design process. The work described here investigates the relationship between human osteoblast attachment, spreading and focal contact formation on selected surfaces using immunostaining and digital image processing for vinculin, a key focal adhesion component. Our observations show that a relationship exists between levels of cell attachment, the degree of vinculin-associated plaque formation and biocompatibility. It also suggests that cell adhesion is not indicative of how supportive a substrate is to cell spreading, and that cell spreading does not correlate with focal contact formation. PMID- 17849223 TI - Expression of an intron-containing beta-tubulin mRNA in catfish olfactory epithelium. AB - Beta-tubulin genes code for very similar proteins, sharing extensive identity in amino acid sequence within and across species, each of which manifests characteristic patterns of cell and tissue expression. While searching for olfactory specific mRNAs in the channel catfish (Ictalurus punctatus), we isolated a novel beta-tubulin cDNA. In the putative ORF, 1298 nucleotides were 80 88% identical to cloned cDNAs from zebrafish to human for beta-tubulin isotype IVb. This ORF is interrupted by an insert of 111 nucleotides located between the regions corresponding to exons 2 and 3 in other species. This insert lacks similarity to any sequence in the NCBI databases. We showed that this novel cDNA fragment hybridizes specifically to catfish olfactory epithelium mRNA on Northern analysis. Here we demonstrate by in situ analysis of catfish olfactory epithelium that the expression of this mRNA is spatially restricted to the outer two-thirds of each olfactory lamella where olfactory receptor neurons reside. These results suggest that this nucleotide sequence is the result of incomplete RNA transcript processing. The growing awareness of the regulatory roles played by RNAs transcribed from intronic regions of genes suggests that this observation may have relevance to regulation of gene expression in olfactory tissue during development and axon targeting. PMID- 17849224 TI - Sustained release and osteogenic potential of heparan sulfate-doped fibrin glue scaffolds within a rat cranial model. AB - This paper explores the potential therapeutic role of the naturally occurring sugar heparan sulfate (HS) for the augmentation of bone repair. Scaffolds comprising fibrin glue loaded with 5 microg of embryonically derived HS were assessed, firstly as a release-reservoir, and secondly as a scaffold to stimulate bone regeneration in a critical size rat cranial defect. We show HS-loaded scaffolds have a uniform distribution of HS, which was readily released with a typical burst phase, quickly followed by a prolonged delivery lasting several days. Importantly, the released HS contributed to improved wound healing over a 3 month period as determined by microcomputed tomography (microCT) scanning, histology, histomorphometry, and PCR for osteogenic markers. In all cases, only minimal healing was observed after 1 and 3 months in the absence of HS. In contrast, marked healing was observed by 3 months following HS treatment, with nearly full closure of the defect site. PCR analysis showed significant increases in the gene expression of the osteogenic markers Runx2, alkaline phosphatase, and osteopontin in the heparin sulfate group compared with controls. These results further emphasize the important role HS plays in augmenting wound healing, and its successful delivery in a hydrogel provides a novel alternative to autologous bone graft and growth factor-based therapies. PMID- 17849226 TI - Emission of volatile organic sulfur compounds from a heavily polluted river in Guangzhou, South China. AB - Emissions of five volatile organic sulfur compounds (VOSCs), including methanethiol, carbonyl sulfide, dimethyl sulfide, carbon disulfide, and dimethyl disulfide, from a heavily polluted river, Shijing River in Guangzhou of South China, was studied. The results showed that the amounts of all VOSCs emitted from the river increased from downstream to upstream along the river with increasing magnitude of water pollution. The emission of carbonyl sulfide was the highest among the target analytes, ranging from 23.8 microg m(-2) h(-1) to 42.6 microg m( 2) h(-1) at the water surface of Shijin River. The concentration levels of VOSCs on the riverbank were lower than those at the water surface either in Shijing River or in Liuxi River. However, the contribution of dimethyl disulfide to the total VOSCs on the riverbank was higher than that at the water surface in most sampling sites, indicating that there might be a point source of dimethyl disulfide on the riverbank besides diffusion from water surface. The 24-h semi continuous monitoring data revealed that the emissions of VOSCs at the water surface peaked at 9:00 and 21:00, which was consistent with the water quality variability in Shijin River caused by daily tidal variation. PMID- 17849227 TI - Size and resin fractionations of dissolved organic matter and trihalomethane precursors from four typical source waters in China. AB - Dissolved organic matter (DOM) and its potential to form disinfection by-products (DBPs) during drinking water treatment raise challenges to water quality control. Understanding both chemical and physical characteristics of DOM in source waters is key to better water treatment. In this study, the DOM from four typical source waters in China was fractionated by XAD resin adsorption (RA) and ultrafiltration (UF) techniques. The trihalomethane formation potential (THMFP) of all fractions in the DOM were investigated to reveal the major THM precursors. The fraction distributions of DOM could be related to their geographical origins in a certain extent. The dominant chemical fraction as THM precursors in the DOM from south waters (East-Lake reservoir in Shenzhen and Peal rivers in Guangzhou) was hydrophobic acid (HoA). The size fraction with molecular weight (MW) <1 kDa in both south waters had the highest THMFP. The results of cluster analysis showed that the parameters of fractions including DOC percentage (DOC%), UV254%, SUVA254 (specific UV254 absorbance) and THMFP were better for representing the differences of DOM from the studied waters than specific THMFP (STHMFP). The weak correlation between SUVA254 and STHMFP for either size or XAD fractions suggests that whether SUVA254 can be used as an indicator for the reactivity of THM formation is highly dependent on the nature of organic matter. PMID- 17849228 TI - Preliminary investigation of sensitive biomarkers of trace metal pollution in mussel (Mytilus galloprovincialis) from Izmir Bay (Turkey). AB - The aim of this study was to identify possible relationships between biochemical- superoxide dismutase (SOD), glutathione peroxidase (GPx), thiobarbituric acid reactive substances (TBARS) of mussels (Mytilus galloprovincialis) and chemical (Hg, Cd, Pb, Cr, Cu, Zn, Mn and Fe) contaminants from relatively clean area (Middle Bay) and heavily polluted area (Inner Bay) of the Izmir Bay. Sampling of mussels was performed in the beginning of May 2004. Mussel digestive glands have been used for biochemical assays. Trace metal content was determined by atomic absorption spectrophotometer using standard procedures. Metal contents in mussels collected at polluted site increased compared to the middle part of the bay. While there was a positive correlation between metals and SOD enzyme activity, there was a negative correlation between metals and GPx enzyme activity. An increase was observed in SOD enzyme activity and a decrease of GPx enzyme activity at the inner part of the bay. PMID- 17849229 TI - Humidity and illumination organic semiconductor copper phthalocyanine sensor for environmental monitoring. AB - In this investigation properties of organic semiconductor copper phthalocyanine (CuPc) capacitive humidity and illumination sensors were studied. Organic thin film was deposited by vacuum evaporation on a glass substrate with silver surface type electrodes to form the Ag/CuPc/Ag sensor. The capacitance of the samples was evaluated at room temperature in the relative humidity range of 35-92%. It was observed that capacitance of the Ag/CuPc/Ag sensor increases with increase in humidity. The ratio of the relative capacitance to relative humidity was about 200. It is assumed that in general the capacitive response of the sensor is associated with polarization due to absorption of water molecules and transfer of charges (electrons and holes). It was observed that under filament lamp illumination of up to 1,000 lx the capacitance of the Ag/CuPc/Ag photo capacitive detectors increased continuously by 20% as compared to dark condition. It is assumed that photo capacitive response of the sensor is associated with polarization due to transfer of photo-generated electrons and holes. An equivalent circuit of the Ag/CuPc/Ag capacitive humidity and illumination sensor was developed. Humidity and illumination dependent capacitance properties of this sensor make it attractive for use in humidity and illumination multi-meters. The sensor may be used in instruments for environmental monitoring of humidity and illumination. PMID- 17849230 TI - Changes in metabolite, energy metabolism related enzyme activities and peripheral blood mononuclear cell (PBMC) populations in beef heifers with two differing liveweight change profiles in New Zealand. AB - Metabolite and immunoreactive insulin (IRI) concentrations, energy metabolism related enzymes activities and peripheral blood mononuclear cell (PBMC) populations were measured in blood of pregnant Angus heifers with differing liveweight change profiles (gaining or losing), in New Zealand to investigate the meanings of those parameters in the restricted feeding beef heifers. Beef heifers losing liveweight (-412 g/day) showed significantly lower concentrations of plasma IRI, and higher concentrations of plasma free fatty acid (FFA) than heifers gaining liveweight (483 g/day). The cytosolic and mitochondrial malate dehydrogenase (MDH) activities and MDH/lactate dehydrogenase (M/L) ratio in leukocytes of the liveweight losing heifers were significantly higher than those the liveweight gaining heifers. Percentages of cluster of differentiation (CD) 3 positive cells and natural killer (NK) cells in PBMC decreased significantly in the liveweight losing heifers compared to those in the liveweight gaining heifers. Plasma IRI and FFA concentrations, leukocyte cytosolic and mitochondrial MDH activities and CD3 positive and NK cell populations may be useful markers to evaluate metabolic conditions and immunity in the restricted feeding beef heifers. PMID- 17849231 TI - Effect of dichromate on photosystem II activity in xanthophyll-deficient mutants of Chlamydomonas reinhardtii. AB - The photosystem II activity and energy dissipation was investigated when algal Chlamydomonas reinhardtii genotypes were exposed to dichromate toxicity effect. The exposure during 24 h to dichromate effect of two C. reinhardtii mutants having non-functional xanthophylls cycle, as npq1 zeaxanthin deficient and npq2 zeaxanthin accumulating, induced inhibition of PSII electron transport. After dichromate-induced toxicity, PSII functions of C. reinhardtii mutants were investigated under different light intensities. To determine dichromate toxicity and light intensity effect on PSII functional properties we investigated the change of energy dissipation via PSII electron transport, non-photochemical regulated and non-regulated energy dissipation according to Kramer et al. (Photosynth Res 79:209-218, 2004). We showed the dependency between dichromate toxicity and light-induced photoinhibition in algae deficient in xanthophyll cycle. When algal mutants missing xanthophylls cycle were exposed to dichromate toxicity and to high light intensity energy dissipation via non-regulated mechanism takes the most important pathway reaching the value of 80%. Therefore, the mutants npq1 and npq2 having non-functional xanthophylls cycle were more sensitive to dichromate toxic effects. PMID- 17849232 TI - Failure to detect Fabry patients in a cohort of prematurely atherosclerotic males. AB - Fabry disease, or alpha-galactosidase A (alpha-Gal A) deficiency, is a lysosomal storage disorder in which accumulation of globotriaosylceramide (Gb(3)) is thought to be responsible for the development of renal, cardiac and cerebral complications. The availability of enzyme replacement therapy has led to an increased awareness and the screening of patients suffering from complications that may be associated with Fabry disease. An association between alpha-Gal A deficiency and atherosclerosis has been suggested, although there is controversy. We therefore studied the prevalence of Fabry disease in a Dutch cohort of prematurely atherosclerotic males. Measurement of alpha-Gal A activity was performed in plasma of 440 Dutch male patients with premature atherosclerosis. Patients were included if they were under the age of 50 years and had proven coronary and/or peripheral artery disease. Analysis revealed a mean alpha-Gal A activity of 7.75 +/- 3.48 nmol/h per ml (range 0.55-34.36). In 425 patients (96.5%) alpha-Gal A activity was within the reference range (3.2-14.3 nmol/h per ml, based on historical controls); 13 patients (3%) had values above and 2 patients (0.5%) below the reference range. Additional analysis of alpha-Gal A activity in leukocytes and fresh plasma in these two patients revealed normal values (53 and 47 nmol/h per mg (reference range: 32-60 nmol/h per mg) and 31.1 and 14.2 nmol/h per ml, respectively). Thus Fabry disease was not detected, leading to an overall prevalence of 0% (95 CI 0-0.68). In conclusion, screening for Fabry disease in prematurely atherosclerotic patients seems not to be very useful, although a slightly increased prevalence is not excluded. PMID- 17849233 TI - Proposal for the prevention of osteoporosis in paediatric patients with classical galactosaemia. AB - Decreased bone mass in early childhood is an increasingly recognized problem in classical galactosaemia as in many other chronic diseases. Peak bone mass is reached in late adolescence; thus, increasing peak bone mass in childhood can prevent osteoporosis. Regular bone mass measurements and preventive treatment should begin in childhood. In the absence of evidence-based guidelines for identification and treatment of decreased bone mass in children, we provide a proposal based on our experience and the available literature. Dual-energy x-ray absorptiometry (DXA) should be used for bone mass assessment. Because cooperation is required, measurements can usually be performed from the age of 4 years. Interpretation of bone mass measurements is crucial for the diagnosis of osteopenia or osteoporosis. In children and adolescents, total body bone mineral content (BMC) as well as lean tissue mass (LTM) should be measured. Comparison of BMC corrected for LTM of the patient with the BMC corrected for LTM of healthy controls allows correction for the confounding effect of bone size. DXA should be repeated every two years in case of normal BMC, as this is the time window in which abnormalities become measurable. If BMC is between 0 and -1 SD, lifestyle factors such as physical activity, intake of calcium and vitamins K and D and oestrogen supplementation (in girls) should be optimized. If BMC is below -1 SD, we advise to start with supplementation of calcium, vitamin K(1) and vitamin D(3). DXA should be repeated yearly in case of BMC below 0 SD in order to identify deteriorations and improvements early. PMID- 17849234 TI - Role of cardiac computed tomography and magnetic resonance imaging in the evaluation of acute chest pain in the emergency department. AB - Evaluation of patients presenting with chest pain to the emergency department remains a challenging task because of a variety of etiologies that range from benign to potentially fatal. Although majority of patients do not have myocardial ischemia as the cause of their presentation, the clinical work up can be time consuming, costly and inconclusive. Recent technical advances in cardiac computed tomography and magnetic resonance imaging have led to better diagnostic accuracy in evaluating patients with chest pain. In this paper, we review the role of cardiac computed tomography and magnetic resonance imaging in evaluating patients with chest pain in the emergency department. PMID- 17849235 TI - Diagnostic accuracy of quantitative cardiac MRI evaluation compared to stress single-photon-emission computed tomography. AB - BACKGROUND: Cardiac MRI (cMRI) perfusion is a promising non-invasive tool to assess myocardial ischemia. The accuracy of quantitative cMRI perfusion has been recently demonstrated, but to date no previous study has compared this technique with stress single-photon-emission computed tomography (SPECT). The aim of this study was to evaluate the diagnostic accuracy of myocardial perfusion reserve (MPR) based on cMRI compared with SPECT. METHODS: We examined 24 patients who underwent coronary angiography, stress SPECT and cMRI perfusion. Qualitative assessment of both SPECT and cMRI images, quantification of cMRI perfusion, and quantitative coronary angiography (QCA) were independently performed. MPR was calculated using Fermi deconvolution technique. Accuracy of quantitative and qualitative data was examined to detect > 50% diameter stenosis (DS) by QCA. RESULTS: Qualitative analysis was obtained in 198 segments and quantitative analysis was performed in 171 segments. Significant coronary artery disease (CAD) was present in 81.8% of patients. Visual cMRI assessment yielded sensitivity of 74.4% and specificity of 79.4% to predict > 50%DS, while SPECT showed sensitivity of 67.4% and specificity of 81.3%. The sensitivity for SPECT in the right coronary artery territory and apex was low compared to cMRI. Sensitivity and specificity for detection of significant CAD were 89.5% and 46.6% for MPR (cutoff 1.92). Area under the curve was 0.75 for MPR (P < 0.01). CONCLUSIONS: The diagnostic accuracy of qualitative examination of perfusion cardiac MRI and stress SPECT were comparable. The high sensitivity and low operator dependency of quantitative cMRI makes it an attractive tool to evaluate myocardial perfusion. PMID- 17849236 TI - Quantification of atherosclerotic coronary plaque components by submillimeter computed tomography. AB - BACKGROUND: Although several investigations have shown that multi-detecor row computed tomography (MDCT) of the coronary arteries can detect noncalcified atherosclerotic plaque, it has remained unresolved if the method also determines features of a rupture-prone plaque. We set out to correlate the size of atherosclerotic plaque components with cardiac MDCT with histology. METHODS AND RESULTS: In 30 autopsy cases, hearts were isolated, coronary arteries filled with contrast agent, and depicted with a clinical 16-row detector CT with a slice thickness of 0.63 mm. Transections of the three main coronary arteries were reconstructed and compared with histopathologic sections using light microscopy. MDCT measurements of total plaque area (r = 0.73, P < 0.0001) and calcified plaque area (r = 0.83, P < 0.0001) correlated well with histopathology, while measurements of non-calcified plaque area (r = 0.53, P < 0.0001) and lipid core size (r = 0.43; P < 0.0001) correlated less well. MDCT overestimated all plaque areas except lipid core size, which was underestimated. CONCLUSIONS: Coronary CT provides an accurate and reproducible method for the quantitative assessment of total plaque and calcified plaque areas. However, the method is less accurate for the quantification of non-calcified plaque area and lipid core size, which is ascribed to limited spatial and contrast resolution. With the present technique, the detection of vulnerable plaques by MDCT remains uncertain. PMID- 17849237 TI - Evaluation of left atrial systolic function in noncompaction cardiomyopathy by real-time three-dimensional echocardiography. AB - BACKGROUND: Noncompaction cardiomyopathy (NCCM) is a rare disorder with persistance of the embryonic pattern of myoarchitecture. NCCM is characterized by loosened, spongy myocardium associated with a high incidence of systolic and diastolic left ventricular (LV) dysfunction and heart failure (HF). It is known that LV dysfunction contributes to elevated left atrial (LA) and pulmonary vascular pressures, however atrial function has not been examined in NCCM. The objective of the present study was to assess LA systolic function characterized by LA ejection force (LAEF) in NCCM patients using real-time three-dimensional echocardiography (RT3DE) and to compare to control subjects. METHODS: The study comprised 17 patients with an established diagnosis of NCCM and their results were compared to 17 healthy age-matched controls with no evidence of cardiovascular disease. Forty-one percent of NCCM patients were in NYHA functional class II / III HF. Previously proposed echocardiographic diagnostic criteria for NCCM were used. All patients underwent conventional two-dimensional echocardiography and RT3DE. LAEF was measured based on MA annulus diameter (LAEF 3D-MAD) and area (LAEF 3D-MAA) using RT3DE. RESULTS: The presence and severity of mitral regurgitation were more frequent in NCCM patients than in control subjects. LV diameters and mitral annulus were significantly increased in NCCM patients. Compared with control subjects, both LAEF 3D-MAD (3.8 +/- 2.2 vs 2.3 +/ 1.0 kdyne, P < 0.05) and LAEF 3D-MAA (12.7 +/- 7.6 vs 4.9 +/- 2.1 kdyne, P < 0.01) were significantly increased in NCCM patients. CONCLUSIONS: LAEF as a characteristic of LA systolic function is increased in NCCM patients compared to normal individuals. These results can suggest compensating left atrial work against the dysfunctional LV in NCCM patients. PMID- 17849238 TI - Health-related quality of life in patients after lumbar disc surgery: a longitudinal observational study. AB - OBJECTIVES: Objectives of this study are (1) to compare health-related quality of life (HRQOL) of patients after lumbar disc surgery with reference data from the German general population; (2) to examine whether changes in HRQOL occur over time; (3) to investigate associations between HRQOL and socio-demographic and health-related factors. METHODS: The study sample consisted at baseline of 189 patients who underwent lumbar disc surgery. Baseline assessment was carried out 1 4 days after surgery, the first follow-up 2 months, the second follow-up 6 months after surgery. HRQOL was assessed by means of the WHOQOL-BREF. RESULTS: During follow-up, patients showed significant improvement in "physical well being" and "overall quality of life." However, it did not reach the level of the general population at any assessment point. There was also a slight improvement of "psychological well being." The domains "social relationships" and "environment" remained unchanged and showed persistently higher scores than the general population. Cohabitating was positively associated with QoL. Negatively associated were unemployment, part-time employment, desire for early retirement, higher intensity of pain and depression. CONCLUSION: Supplementing physical rehabilitation by psychosocial interventions may help improve patients' HRQOL. PMID- 17849242 TI - Dextromethorphan poisoning: an evidence-based consensus guideline for out-of hospital management. AB - The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial out-of-hospital management of patients with a suspected ingestion of dextromethorphan by 1) describing the process by which an ingestion of dextromethorphan might be managed, 2) identifying the key decision elements in managing cases of dextromethorphan ingestion, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This guideline applies to the ingestion of dextromethorphan alone. Co-ingestion of additional substances could require different referral and management recommendations depending on the combined toxicities of the substances. This guideline is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions might be at variance with this guideline and are the prerogative of the patient and the health professionals providing care, considering all of the circumstances involved. This guideline does not substitute for clinical judgment. The grade of recommendation is in parentheses. 1) All patients with suicidal intent, intentional abuse, or in cases in which a malicious intent is suspected (e.g., child abuse or neglect) should be referred to an emergency department (Grade D). 2) Patients who exhibit more than mild effects (e.g., infrequent vomiting or somnolence [lightly sedated and arousable with speaking voice or light touch]) after an acute dextromethorphan ingestion should be referred to an emergency department (Grade C). 3) Patients who have ingested 5-7.5 mg/kg should receive poison center-initiated follow-up approximately every 2 hours for up to 4 hours after ingestion. Refer to an emergency department if more than mild symptoms develop (Grade D). 4) Patients who have ingested more than 7.5 mg/kg should be referred to an emergency department for evaluation (Grade C). 5) If the patient is taking other medications likely to interact with dextromethorphan and cause serotonin syndrome, such as monoamine oxidase inhibitors or selective serotonin reuptake inhibitors, poison center-initiated follow-up every 2 hours for 8 hours is recommended (Grade D). 6) Patients who are asymptomatic and more than 4 hours have elapsed since the time of ingestion can be observed at home (Grade C). 7) Do not induce emesis (Grade D). 8) Do not use activated charcoal at home. Activated charcoal can be administered to asymptomatic patients who have ingested overdoses of dextromethorphan within the preceding hour. Its administration, if available, should only be carried out by health professionals and only if no contraindications are present. Do not delay transportation in order to administer activated charcoal (Grade D). 9) For patients who have ingested dextromethorphan and are sedated or comatose, naloxone, in the usual doses for treatment of opioid overdose, can be considered for prehospital administration, particularly if the patient has respiratory depression (Grade C). 10) Use intravenous benzodiazepines for seizures and benzodiazepines and external cooling measures for hyperthermia (>104 degrees F, >40 degrees C) for serotonin syndrome. This should be done in consultation with and authorized by EMS medical direction, by a written treatment protocol or policy, or with direct medical oversight (Grade C). 11) Carefully ascertain by history whether other drugs, such as acetaminophen, were involved in the incident and assess the risk for toxicity or for a drug interaction. PMID- 17849243 TI - Toxicity of two North American Loxosceles (brown recluse spiders) venoms and their neutralization by antivenoms. AB - The toxic, biochemical, and immunological characteristics of L. boneti and L. reclusa venoms and its neutralization by anti-L. boneti and anti-L. reclusa antivenoms were studied. The electrophoretic profile showed very similar patterns and the toxic activities were very close. Immunological studies showed cross reactivity among L. boneti and L. reclusa venoms, with L. boneti and L. reclusa experimental antivenoms, and anti-L. gaucho and anti-L. laeta antivenoms. The venom of L. laeta showed low immunological reactivity with the North American Loxosceles antivenoms. Experimental anti-North American Loxosceles antivenoms protected mice of the systemic toxicity and were able to prevent necrosis in rabbit skin after the injection of the venom. Both antivenoms displayed cross neutralization. The results showed that both Loxosceles venoms have very close toxic, biochemical, and immunological characteristics, and that either monospecific antivenoms or an antivenom raised with L. boneti and L. reclusa venoms as immunogens could be useful for treating bites by North American Loxosceles spiders. PMID- 17849244 TI - Significance of copper determination in late onset of Wilson's disease. AB - BACKGROUND: Wilson's disease is an autosomal recessive disorder of copper metabolism resulting from the dysfunction of a copper transporting P-type ATPase encoded on chromosome 13. When capacity for hepatic storage is exceeded, the excess copper manifests itself in toxic action. In this article, the case of a sudden unexpected death of a 22-year-old woman, as a result of a subclinical course of Wilson's disease, is reported. METHODS/RESULTS: A woman with no past medical history of underlying liver disease was hospitalized for nine days before death because of strong hemolytic anemia of unknown origin. Intoxication by lead, mercury, cadmium, thallium, zinc, chromium, manganese, and arsenic compounds was excluded. High levels of copper in blood and urine (AAS method) were found (blood: 3.90 microg/ml, urine: 8.10 microg/ml, 12,140 microg/24 h; normal - blood: 0.88 microg/ml, urine: 0.051 microg/ml, < 51 microg/24 h). Symptomatic treatment, aimed at multi-organ failure, was applied immediately. In spite of intensive care, the patient died. Post-mortem findings indicated the presence of anasacra and ascites, hydropericardium, brain edema, orange-like coloration of internal organs, and cirrhotic liver. Histopathological examination of liver slices revealed complete micro- and medionodular cirrhotic changes, focal central necrosis of the hepatocytes and cholestasis. The copper content in liver was 89.8 mug/g (normal: 3.58 +/- 1.71 microg/g). CONCLUSIONS: Assessment of tissue copper content is essential for the diagnosis of Wilson's disease in the living or after death (in living it can be helpful in proper diagnosis, and after death it enables one to ascertain the cause of a sudden death). The copper level in the liver in Wilson's disease is about 25 times higher than in the healthy liver. PMID- 17849245 TI - Ciguatoxin-like substances in edible fish on the eastern Mediterranean. AB - BACKGROUND: The consumption of edible fish (e.g., Siganus spp) was assumed to have caused ciguatera poisoning at an atypical site, the eastern Mediterranean. This pilot study assesses the presence of ciguatoxin-like substances in edible fish on the eastern Mediterranean coast of Israel. METHODS: Samples of Siganus rivulatus from polluted seawater (Haifa Bay), Siganus rivulatus from relatively clean seawater (Dor), and fish from the freshwater Sea of Galilee not inhabited by toxic algae were analyzed during summertime. Ciguatoxin-like substances were tested by a membrane immunobead assay that yields a color reaction (positive, weakly positive, negative). RESULTS: Significantly more large and small fish from Haifa Bay yielded positive color reactions compared to fish from Dor. Sea of Galilee fish gave no positive color reactions. CONCLUSIONS: Our results suggest the presence of ciguatoxin-like substances in edible fish of the eastern Mediterranean. Additional analyses are needed to determine whether these substances are ciguatoxins or related polyethers. PMID- 17849246 TI - A case of mixed intoxication with isopropyl alcohol and propanol-1 after ingestion of a topical antiseptic solution. AB - We report a mixed intoxication with isopropyl alcohol and propanol-1 in a hospitalized patient who ingested, on two separate days, two 100 ml bottles of a topical antiseptic solution containing isopropyl alcohol and propanol-1. Eight hours after the second ingestion, plasma concentrations of isopropanol, propanol 1 and acetone were 37 mg/dL, <10 mg/dL, and 227 mg/dl, respectively. Despite a lack of severe toxicity, 4-methylpyrazole (fomepizole) was initiated. This case points out the need to limit access to alcohol-containing antiseptic solutions on wards where alcoholic and psychotic patients are hospitalized. PMID- 17849247 TI - Does age matter? Comparing case fatality rates for selected poisonings reported to U.S. poison centers. AB - BACKGROUND: As the elderly population continues to grow, the number of geriatric patients reported to poison centers continues to increase. We believe that older poisoned patients are at an increased risk of death compared to younger adult patients. The objective of this study was to compare the risk of death from selected poisoning between younger (<59) and older (>59) adults. METHODS: We included adult cases reported to U.S. poison centers between 1995 and 2002. To limit potential confounders, our analysis included single substance ingestions of theophylline, digoxin, benzodiazepines, tricyclic antidepressants, calcium channel antagonists, acetaminophen, and salicylate. We determined the case fatality rate for each poisoning for younger and older adults. We calculated crude odds ratios for each poison and then used logistic regression to adjust for covariates. RESULTS: Overall we found an increase in the relative rate of death for each poison (range 1.2 to 7.1). After adjustment, each 10-year increase in age was associated with a 36% increase in the odds ratio for death as an outcome. Our findings were limited by the use of poison center data, which does not include data on covariates that may be potential confounders. PMID- 17849248 TI - Death due to anaphylactic shock secondary to intravenous self-injection of Toradol: a case report and review of the literature. AB - A fatality due to the intravenous self-injection of Ketorolac (Toradol) is reported. Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) with marked analgesic activity. There is limited information of fatalities attributed to ketorolac toxicity. Here we report the case of a 53-year-old woman with a medical history of depression that was found deceased at home with no evidence of trauma or injuries. Near the body, a syringe and three empty vials (30 mg) of Toradol were found. A fresh needle mark on the right arm was noticed. Toxicological analyses were performed using a gas chromatography-mass spectrometry (GC/MS) technique. The estimated ketorolac concentration in the blood was 8 mug/ml; urine and gastric content were negative for this compound. Based on the autopsy, histologic findings and toxicological results of anaphylactic shock associated with ketorolac self-administration was assumed to be the underlying pathophysiological mechanism of death and the manner, suicide. PMID- 17849249 TI - Acute respiratory distress syndrome resulting from inhalation of powdered copper. AB - BACKGROUND: Copper is an essential element. Poisoning with elemental copper is infrequent and manifestations rarely include the ones that our case presented. CASE REPORT: A previously healthy 2-year-old female patient unintentionally inhaled copper dust, developed respiratory failure a few hours later, and required mechanical ventilation. On hospital day three, the patient developed acute respiratory distress syndrome and was treated with high-frequency oscillatory ventilation for six days. She also developed hemolytic anemia, liver failure, oliguric renal failure, and evidence of acute tubular injury. During her stay in the intensive care unit she received inotropic support, packed red cells transfusion, and diuretics. A sample of bronchoalveolar lavage showed macrophages that stained positive for copper. Serum and urine copper concentrations were within the normal range after several days. Extubation was successfully achieved after two weeks and the patient was discharged on day 30 without sequelae. This is the first report of acute respiratory distress syndrome secondary to copper aspiration in a pediatric patient. CONCLUSION: To our knowledge, this is the first case reported of acute respiratory distress syndrome secondary to elemental copper aspiration. It is important to the clinician to be aware of acute respiratory distress syndrome as a differential diagnosis to copper aspiration by treating the patient aggressively in an adequate clinical setting. PMID- 17849250 TI - Methanol poisoning in Tunisia: report of 16 cases. AB - Methanol poisoning continues to be a public health problem in Tunisia in spite of the different legislative measures. We report a series of 16 cases of methanol poisoning admitted to our Intensive Care Unit between December 2003 and April 2004. The patients' median age was 21.5 years (range 16 to 53 years) with a median SAPS II of 14 (range 12 to 84) and an APACHE II of 8 (range 6 to 36). The median latent period was 9.5 hours (range 4 to 24 hours) with a delay to medical consultation of 36 hours (range 6 to 48 hours), and a median serum methanol concentration of 1.4 g/L (range 0.19 to 3.62 g/L). Clinical signs included central nervous system symptoms (69%), gastrointestinal complaints (87%), visual disturbances (69%) and metabolic acidosis (94%). Three patients (19%) required mechanical ventilation because of deep coma or shock and died within 6 hours. Hemodialysis was performed in eleven patients (69%) because of visual disturbances and/or metabolic acidosis. One patient developed irreversible bilateral blindness and another unilateral blindness secondary to optic neuropathy. Statistical significant risk factors for the developing of visual disturbances were found to be the ingested quantity of methanol, the latent period, acidosis and serum methanol concentration on admission. PMID- 17849251 TI - Severe acute arsine poisoning treated by plasma exchange. AB - INTRODUCTION: Exposure to arsine gas can cause fatal hemolysis and multiorgan damage. Whole blood exchange transfusion and hemodialysis have been recommended to treat severe acute arsine poisoning, but are associated with significant complications and sub-optimal outcomes. Plasma exchange is another method of blood purification technique but there are no data on its use in acute arsine poisoning. This retrospective study evaluated the clinical and effects and arsenic clearance from the use of plasma exchange treatment of patients with acute arsine poisoning. METHODS: Data from patients with severe acute arsine poisoning, treated with plasma exchange from December 2000 to December 2005 were collected and analyzed. Measured laboratory factors, performed before and after plasma exchange treatment included routine biochemistry and hematology tests as well as arsenic concentrations in blood, urine, and discarded plasma. RESULTS: During the study period, 12 patients with severe acute arsine poisoning were treated with plasma exchange. Plasma exchange was performed one or two times on each patient, during which the replacement fluid was fresh frozen plasma (total volume ranged from 1,400 to 4,000 mL). The range of concentrations of arsenic in discarded plasma was 27.7 to 88.7 mg/L and the range of total arsenic removed by plasma exchange was 55.4 to 177.4 mg. Plasma exchange appears to rapidly terminate arsine-induced hemolysis and favorably modify damage to the kidneys and other organs. Laboratory factors that showed significant association with treatment response were creatine kinase, lactate dehydrogenase, blood urea nitrogen, total bilirubin, and heart-related enzymes. All patients recovered from the poisoning and were in good condition at a 2 to 3 months follow-up. CONCLUSIONS: Plasma exchange appears to be an effective treatment intervention for patients with severe acute arsine poisoning. It is suggested that it be used as early as possible. PMID- 17849252 TI - Reversible myocardial injury associated with aluminum phosphide poisoning. AB - BACKGROUND: Aluminum phosphide poisoning has high mortality resulting from cardiac impairment and hemodynamic disorders. We report two cases of aluminum phosphide associated with reversible myocardial injury. CASES REPORTS: A 19-year old woman and a 28-year-old man were admitted to hospital following ingestion of aluminum phosphide. The clinical course was characterized by the development of a shock syndrome requiring the use of vasoactive amines in the woman. However, the arterial hypotension in the man was improved by fluid filling and vasoactive drugs. The myocardial injury was objectively documented in both cases. The electrocardiogram showed ST-segment elevations and diffusely abnormal repolarization. The plasma concentrations of cardiac enzymes were elevated. In the second case, echocardiography showed similar myocardial involvement with left ventricular hypokinesis (left ventricle ejection fraction 30%). In both cases, there was progressive improvement in hemodynamic status, cardiac traces, and biochemical values. A simultaneous improvement was observed in echocardiogram of the second case (left ventricle ejection fraction increased to 50%). CONCLUSION: Reversible myocardial injury following aluminum phosphide poisoning has been described in few cases. We objectively documented progressive clinical and electrical improvement in two cases. PMID- 17849253 TI - Hydrofluoric acid burn to penis. PMID- 17849254 TI - Late-onset intermediate syndrome due to organophosphate poisoning. PMID- 17849255 TI - Gastric bezoar following venlafaxine overdose. PMID- 17849257 TI - Novel delivery systems for interferons. AB - Interferons, IFNs, are among the most widely studied and clinically used biopharmaceuticals. Despite their invaluable therapeutic roles, the widespread use of IFNs suffers from some inherent limitations, mainly their relatively short circulation lifespan and their unwanted effects on some non-target tissues. Therefore, both these constraints have become the central focus points for the research efforts on the development of a variety of novel delivery systems for these therapeutic agents with the ultimate goal of improving their therapeutic end-points. Generally, the delivery systems currently under investigation for IFNs can be classified as particulate delivery systems, including micro- and nano particles, liposomes, minipellets, cellular carriers, and non-particulate delivery systems, including PEGylated IFNs, other chemically conjugated IFNs, immunoconjugated IFNs, and genetically conjugated IFNs. All these strategies and techniques have their own possibilities and limitations, which should be taken into account when considering their clinical application. In this article, currently studied delivery systems/techniques for IFN delivery have been reviewed extensively, with the main focus on the pharmacokinetic consequences of each procedure. PMID- 17849258 TI - The state of the art in the production of fructose from inulin enzymatic hydrolysis. AB - The present work reviews the main advancements achieved in the last decades in the study of the fructose production process by inulin enzymatic hydrolysis. With the aim of collecting and clarifying the majority of the knowledge in this area, the research on this subject has been divided in three main parts: a) the characteristics of inulin (the process reactant); b) the properties of the enzyme inulinase and its hydrolytic action; c) the advances in the study of the applications of inulinases in bioreactors for fructose production. Many vegetable sources of inulin are reported, including information about their yields in terms of inulin. The properties of inulin that appear relevant for the process are also summarized, with reference to their vegetable origin. The characteristics of the inulinase enzyme that catalyzes inulin hydrolysis, together with the most relevant information for a correct process design and implementation, are described in the paper. An extended collection of data on microorganisms capable of producing inulinase is reported. The following characteristics and properties of inulinase are highlighted: molecular weight, mode of action, activity and stability with respect to changes in temperature and pH, kinetic behavior and effect of inhibitors. The paper describes in detail the main aspects of the enzyme hydrolysis reaction; in particular, how enzyme and reactant properties can affect process performance. The properties of inulinase immobilized on various supports are shown and compared to those of the enzyme in its native state. Finally, a number of applications of free and immobilized inulinases and whole cells in bioreactors are reported, showing the different operating procedures and reactor types adopted for fructose production from inulin on a laboratory scale. PMID- 17849259 TI - The genus Gluconobacter oxydans: comprehensive overview of biochemistry and biotechnological applications. AB - The genus Gluconobacter comprises some of the most frequently used microorganisms when it comes to biotechnological applications. Not only has it been involved in "historical" production processes, such as vinegar production, but in the last decades many bioconversion routes for special and rare sugars involving Gluconobacter have been developed. Among the most recent are the biotransformations involved in the production of L-ribose and miglitol, both very promising pharmaceutical lead molecules. Most of these processes make use of Gluconobacter's membrane-bound polyol dehydrogenases. However, recently other enzymes have also caught the eye of industrial biotechnology. Among them are dextran dextrinase, capable of transglucosylating substrate molecules, and intracellular NAD-dependent polyol dehydrogenases, of interest for co-enzyme regeneration. As such, Gluconobacter is an important industrial microbial strain, but it also finds use in other fields of biotechnology, such as biosensor technology. This review aims to give an overview of the myriad of applications for Gluconobacter, with a special focus on some recent developments. PMID- 17849260 TI - Metabolic engineering of plant L-ascorbic acid biosynthesis: recent trends and applications. AB - Vitamin C (L-ascorbic acid; AsA) is the major soluble antioxidant found in plants and is also an essential component of human nutrition. Although numerous biotechnological methods have been exploited to increase its yield, pressures such as commercial competition and environmental concerns make it urgent to find a new way for industrial production of plant-derived AsA. Engineering plant AsA has now become feasible because of our increased understanding of its biosynthetic pathway. Several possible strategies could be followed to increase AsA production, such as overcoming the rate limiting steps in the biosynthetic pathway, promoting recycling, and reducing catabolism. For these purposes, genes of plant, microbial and animal origins have been successfully used. Several examples will be given to illustrate these various approaches. The existing and potential achievements in increasing AsA production would provide the opportunity for enhancing nutritional quality and stress tolerance of crop plants. PMID- 17849261 TI - Capsule and O-antigen from an extraintestinal isolate of Escherichia coli modulate cytokine levels in rat macrophages in vitro and in a rat model of pneumonia. AB - Gram-negative pneumonia results in significant morbidity, mortality, and cost to the healthcare system. Previously the authors demonstrated that capsule and O antigen, virulence factors of the extraintestinal Escherichia coli isolate CP9, modulate pulmonary neutrophil influx in a rat pneumonia model. In this report, the authors utilized CP9 and mutants deficient in O-antigen (CP921), capsule (CP9.137), or both (CP923) to test the hypothesis that modulation of cytokine levels by capsule and/or O-antigen may be a contributory mechanism. Effects of capsule and O-antigen on cytokine levels in rats in vivo and in isolated pulmonary macrophages in vitro were assessed. In vivo, capsule and O-antigen had no significant effect on tumor necrosis factor (TNF)-alpha levels in bronchoalveolar lavage fluid (BALF), but both were associated with significant increases in the levels of interleukin (IL)-1beta and Cytokine-induced neutrophil Chemoattractant-1 (CINC-1). However, potential difficulties in interpreting data occurred because challenge bacterial strains exhibited differential growth, and clearance characteristics and mixed cell populations were present. Therefore, added mechanistic studies investigated specific interactions of capsule and O antigen with pulmonary macrophages purified from normal rats and exposed to CP9, CP921, CP9.137, or CP923 in vitro. Results indicated that the presence of capsule led to significantly increased levels of TNF-alpha, IL-1beta, and CINC-1, whereas O-antigen significantly decreased macrophage-associated levels of these mediators. These findings support the hypothesis that CP9 capsule is proinflammatory for macrophage-induced neutrophil recruitment, whereas O-antigen attenuates macrophage production of proinflammatory mediators in pneumonia. These results expand our understanding on the mechanisms by which these virulence traits may contribute to the inflammatory pathogenesis of pneumonia. PMID- 17849263 TI - Lipopolysaccharide-induced neutrophilic inflammation in the lungs differs with age. AB - In aged humans and animals, lung injuries are generally more serious and prolonged. From a kinetic perspective, the authors thus assessed whether lung expression of proinflammatory cytokines were altered with age following intratracheal lipopolysaccharide (LPS) challenge in mice. Tumor necrosis factor alpha, interleukin-1beta, macrophage inflammatory protein-1alpha, macrophage inflammatory protein-2, and keratinocyte-derived chemokine were significantly higher in 65-week-old mice along with sustained neutrophilia when compared to 11 week-old mice at 72 hours, but not at earlier time points. The authors concluded that the degree of LPS-induced neutrophilic inflammation and the expression of these cytokines differ with age at later phases of acute lung injury. PMID- 17849262 TI - Imatinib mesylate inhibits fibrogenesis in asbestos-induced interstitial pneumonia. AB - Profibrogeneic cytokines contribute to the accumulation of myofibroblasts in the lung interstitium in idiopathic pulmonary fibrosis (IPF). Imatinib mesylate, a tyrosine kinase inhibitor specific for Abl, platelet-derived growth factor receptor (PDGFR) and c-Kit tyrosine kinases, has been shown to inhibit fibrosis and profibrotic signaling in mouse models of inflammation-mediated lung reactions. The authors tested imatinib mesylate in vivo in a mouse model of crocidolite asbestos-induced progressive fibrosis. The ability of imatinib mesylate to inhibit profibrogeneic cytokine-induced human pulmonary fibroblast migration was tested in vitro and the expression of its target protein tyrosine kinases was assessed with immunofluorescence. In vivo, 10 mg/kg/day imatinib mesylate inhibited histological parenchymal fibrosis and led to a decrease in collagen deposition, but had no significant effect on asbestos-induced neutrophilia. However, 50 mg/kg/day imatinib mesylate did not inhibit collagen deposition. In vitro, IPF fibroblasts expressed Abl, PDGFR-alpha, PDGF-beta, but not c-Kit, and 1 microM imatinib mesylate inhibited profibrogeneic cytokine induced IPF fibroblast migration. These results suggest that imatinib mesylate is a potential and specific inhibitor of fibroblast accumulation in asbestos-induced pulmonary fibrosis. PMID- 17849265 TI - Interleukin-6 and cyclic AMP stimulate release of cathepsin B in human osteoblasts. AB - Previous studies have suggested that cathepsin B participates in the joint destruction associated with rheumatoid arthritis (RA). This study examined the activity of cathepsin B (a lysosomal cysteine protease) in human osteoblasts along with its regulation by cyclic AMP and Interleukin-6 (IL-6). Cyclic AMP elevating agents activate cathepsin B and stimulate the secretion of cathepsin B via the secretion of IL-6, a potent mediator of RA. This study investigated the induction of cathepsin B using the proinflammatory cytokine in human osteoblasts (MG-63) in relation to p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappa B transcription factor. When added to MG-63 cells, IL-6 stimulated the production of cathepsin B, which was reduced significantly by the addition of SB203580, a specific p38 MAPK inhibitor. In addition, the release of IL-6 was also inhibited by either pyrrolidine dithiocarbamate (PDTC) or NF-kappaB SN50, which are potent NF-kappaB inhibitors. Both NF-kappaB inhibitors had a larger inhibitory effect on the activity of cathepsin B in the presence of SB203580. IL-6 stimulated the NF-kappaB binding affinity as well as the activation of p38 MAP kinase, leading to the release of cathepsin B. However, SB203580 had no effect on the IL-6-induced activation of NF-kappaB, and neither of the NF-kappaB inhibitors decreased the level of p38 MAPK activation in the IL 6-stimulated osteoblasts. Moreover, IL-6 increased the activity of urokinase type plasminogen activator (uPA) in MG-63 cells, which was inhibited by SB203580, PDTC and NF-kappaB SN50. This strongly suggests that p38 MAPK and NF-kappaB are essential to the IL-6-induced activation of cathepsin B or uPA and that these two IL-6-activated pathways can act independently. PMID- 17849266 TI - Modulation of cell-mediated immune response in B16F-10 melanoma-induced metastatic tumor-bearing C57BL/6 mice by sulforaphane. AB - Effect of sulforaphane on cell-mediated immune response (CMI) was studied in B16F 10 melanoma-induced metastasis-bearing C57BL/6 mice. Administration of sulforaphane significantly enhanced natural killer (NK) cell activity in metastatic tumor-bearing animals (43.17% cell lysis, on day 5) and the activity was observed earlier than in tumor-bearing control animals (maximum of 9.76% cell lysis, on day 9). Antibody-dependent cellular cytotoxicity also was enhanced significantly in metastatic tumor-bearing animals (41.20% cell lysis on day 9) after sulforaphane administration compared with untreated control tumor-bearing animals (maximum of 12.62% cell lysis on day 15). An early antibody-dependent complement-mediated cytotoxicity also was observed in sulforaphane-treated tumor bearing animals (26% cell lysis, on day 15). Administration of sulforaphane significantly enhanced the production of IL-2 and IFN-gamma in metastatic tumor bearing animals. In addition, sulforaphane significantly downregulated the serum levels of proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha, and GM-CSF during metastasis. These data clearly suggest that sulforaphane effectively inhibited the spread of metastatic tumor cells through the stimulation of CMI, upregulation of IL-2 and IFN-gamma, and downregulation of proinflammatory cytokines IL-1beta, IL-6, TNF-alpha, and GM-CSF. PMID- 17849267 TI - Oral administration of aqueous extract of Carthami Flos induces macrophage activation and preferentially potentiates type 1 helper T-cell response in vivo. AB - In vivo immunomodulatory activity of aqueous extract of Carthami Flos (AECF) was investigated using a mouse model immunized with keyhole limpet hemocyanin. Serum level of Ag-specific IgG2a was significantly elevated by oral administration of AECF but not IgG1. However, no selective B-cell proliferation by AECF was observed in vivo. Ag-specific proliferation and IFN-gamma and IL-5 production of draining lymph node T cells also was higher in AECF-treated mice when compared with water-treated control mice. However, AECF failed to enhance nonspecific T cell response under CD3 stimulation. These results led us to hypothesize that AECF potentiates Ag-specific T-cell response, possibly through activation of antigen presenting cells (APC) other than B cells. Functional assessment of splenic macrophages showed that AECF administration significantly enhances IL-12 production as well as APC activity for IFN-gamma production and STAT-4 activation by T cells. Collectively, these data strongly support that AECF preferentially potentiates immune response polarized toward TH1 and for which increased activation of macrophages is most likely to be responsible. The present data implicate a possible application of AECF to potentiate cellular immunity and, we hope, prevent intracellular infections. PMID- 17849268 TI - Modeling of granulocyte cytoskeletal responses following fMLP challenging. AB - Formyl peptides released from Gram-negative bacteria ligate a group of specific mammalian receptors, expressed mainly on granulocytes, monocytes, and macrophages. Receptor ligation activates different transduction cascades, eventually leading to the release of reactive oxygen species and other bactericidal chemical species, and the activation of the actin cytoskeleton with extension of lamellipodia and migration toward the sites of maximal formyl peptide concentration. In vitro, under conditions of nongradient formyl peptide concentrations, lamellipodia form all around the cell contour (chemokinesis). In granulocytes challenged under these conditions with N-formyl-methionyl-leucyl phenylalanine, (i) the power spectrum of the contour of activated cells shows a peak at a specific periodicity, indicating that the lamellipodial extension is not completely random but stochastically conforms to a deterministic scheme, and (ii) the morphological response (percent of cells exhibiting chemokinesis) tends to reach a maximum at certain drug concentrations, then declining at higher concentrations. Accordingly, the logarithm of the drug concentration-polarizing effect curve is bell-shaped. Herein we illustrate theoretical models for the simulation of these two components of the chemokinetic responses. We show that the main traits of the general morphology and arrangement of lamellipodia may be simulated by an algorithm that starting from a situation of random distribution of active receptors on the cell membrane, encompasses in the successive calculation cycles both a local autocatalytic enhancement of the actin polymerization and a relative inhibition of the actin polymerization at some distance from the more active polymerization foci. In addition, a drug log concentration-polarizing effect bell-shaped curve may be simulated by assuming that the N-formyl-methionyl-leucyl-phenylalanine, while binding with high affinity to the specific receptor, is also able to bind to another lower affinity receptor that may effect depolarizing actions or, more generally, metabolic blocking effects. Under these conditions, at low drug concentrations the polarizing effect brought about by the ligation of the specific receptor is largely predominant. However, as the drug concentration increases and the specific receptors approach saturation, the inhibitory effects become more and more powerful and the net polarizing effect is reduced. PMID- 17849269 TI - Effect of skin sensitizers on inducible nitric oxide synthase expression and nitric oxide production in skin dendritic cells: role of different immunosuppressive drugs. AB - Nitric oxide (NO) is involved in the pathogenesis of acute and chronic inflammatory conditions, namely in allergic contact dermatitis (ACD). However, the mechanism by which NO acts in ACD remains elusive. The present study focuses on the effects of different contact sensitizers (2,4-dinitrofluorbenzene, 1,4 phenylenediamine, nickel sulfate), the inactive analogue of DNFB, 2,4 dichloronitrobenzene, and two irritants (sodium dodecyl sulphate and benzalkonium chloride) on the expression of the inducible isoform of nitric oxide synthase (iNOS) and NO production in skin dendritic cells. It was also studied the role of different immunosuppressive drugs on iNOS expression and NO production. Only nickel sulfate increased the expression of iNOS and NO production being these effects inhibited by dexamathasone. In contrast, cyclosporin A and sirolimus, two other immunosuppressive drugs tested, did not affect iNOS expression triggered by nickel. PMID- 17849270 TI - Formyl peptide receptors on immune and nonimmune cells: analysis of sequence conservation in FPR genes. AB - Formyl peptides are oligopeptides released by Gram-negative bacteria. So far, specific formyl peptide receptors (FPRs) have been described in mammals only. FPRs are seven-transmembrane G-coupled molecules and make up a relatively homogeneous group, although exhibiting different levels of affinity for the ligands. We examined the patterns of conservation/mutation within the FPR group of genes, as studied in 16 mRNAs from different species. Following alignment of the coding sections, those nucleotides identical in at least 15 sequences were assigned a "conservation index" 2; those with 8-14 identities an index 1; those with less than 8 identities an index zero. The cumulative average conservation index was 1.36. The autocorrelation function and the power spectrum of the whole series of indexes demonstrated a 3-unit periodicity. This periodicity is explained by the fact that the average conservation indexes of the first, second and third nucleotides of the coding triplets were 1.46, 1.55 (both above the mean), and 1.06 (below the mean), respectively, so that correlations at lag 3 tend to be all positive. In mRNAs, regardless of the position in the coding triplets, T is significantly more frequently conserved (average index = 1.60) than A, C, and G (1.21 - 1.38). In the nucleotides with conservation index 1 or zero, we recorded the two more frequently represented bases. In 35% of mRNA nucleotides the two more frequently represented bases were C and T; in 28% of cases the two more frequently represented bases were A and G; other couples occurred with lower frequencies. Both mutations may arise following C methylation with subsequent transformation into T (by deamination), either in the template or the coding DNA strand. Thus, we hypothesized that in FPR mRNAs there is an evolutionary trend of transformation from G to A and from C to T, the latter being the more stable of the bases. PMID- 17849271 TI - Flavonoid rutin alters the viability and function of mitogen-stimulated splenocytes and thymocytes compared with non stimulated cells. AB - Rutin is a flavonoid obtained from Dimorphandra mollis (Benth.), a medicinal Brazilian plant used as antioxidative, antihemorrhagic, and blood vessel protector. The present study has examined its effects on the viability and function of immune system cells in vitro. Rat spleen and thymus cells were cultured with 10 nM, 1 microM, and 10 microM of the drug in the presence or absence of PWM, LPS, or ConA mitogens. Cellular proliferation was analyzed by H(3)-thymidin uptake and IFN-gamma and IL-10 were measured by ELISA after 48 and 72 hr. Viability was measured by flow cytometry using Annexin V and PI after 24 and 48 hr. The flavonoid rutin inhibited splenocytes and thymocytes proliferation under ConA stimulation observed by an increase on apoptosis levels of thymocytes stimulated with PWM in 24 hr and on splenocytes stimulated with PWM in 48 hr. Function studies showed a decrease on IFN-gamma production by splenocytes and thymocytes stimulated with PWM or ConA. Spleen cells cultured with LPS and rutin showed a decrease on apoptosis after 24 hr and an increase on the IL-10 levels after 48 hr. There was no significant variation on the necrosis rate, viability, and function of cells treated with rutin in the absence of mitogenic stimulus. PMID- 17849272 TI - The Effect of N-nitrosodimethylamine on TRAIL and DR5 expression in human neutrophils--preliminary study. AB - The intracellular mechanisms of NDMA-induced apoptosis of neutrophils have not yet been fully understood. The aim of this study was to explain whether the TRAIL/DR5 system is implicated in NDMA-induced apoptosis of human neutrophils. The expression of TRAIL and DR5 was examined, as well as the secretion of sTRAIL and sDR5 by human neutrophils treated with NDMA confronted with intensity apoptosis of these cells. For comparative purposes similar examinations in autologous peripheral blood mononuclear cells (PBMC) were performed. Decreased expression and secretion of TRAIL and increased expression and secretion of DR5 associated with increased intensity of apoptosis of polymorphonuclear leukocytes (PMNs) suggest that NDMA-induced apoptosis in these cells may be depend on TRAIL/DR5 system. Autologous PBMCs no exerted that changes in the expression and secretion of TRAIL as well as in the intensity of apoptosis. However, the expression and secretion of DR5 by PBMCs were similar to those by PMNs. Differences above suggest that PMNs are more sensitive to unfavorable action of NDMA than PBMCs. PMID- 17849273 TI - Effect of hydrogen peroxide on interleukin-8 synthesis and death of Caco-2 cells. AB - Intestinal epithelial cells can secrete interleukin-8 (IL-8), among other substances in response to different stimuli, which plays an important role in mucosal immune response. Above a certain concentration range, hydrogen peroxide causes cell death by necrosis or apoptosis. We investigated the time- and dose dependent induction of IL-8 by hydrogen peroxide in the human colon adenocarcinoma cell line Caco-2. In addition, the changes of transepithelial electrical resistance and cell death induction in response to hydrogen peroxide were studied. Nonfilter-grown and filter-grown Caco-2 cells were employed in our experiments. Interleukin-8 synthesis was measured by ELISA. Necrosis was determined by DAPI staining of cells, apoptosis by measuring caspase-3 enzyme activity or annexin V staining. In nonfilter-grown Caco-2 cells, 1 mM of hydrogen peroxide induced the highest level of IL-8 production 24 hr after treatment. In filter-grown Caco-2 cells, IL-8 was produced only on the apical side in response to 1 mM of hydrogen peroxide. This level was 10-fold lower than that measured in nonfilter-grown Caco-2 cells 24 hr after the treatment. In filter-grown Caco-2 cells 10 mM hydrogen peroxide induced the highest IL-8 level on the apical as well as basolateral side. Transepithelial electrical resistance decreased markedly upon application of 40 mM hydrogen peroxide. Late effect of hydrogen peroxide was observed in nonfilter-grown Caco-2 cells, as 1 mM hydrogen peroxide caused necrosis after 24 hr while early-necrosis induction occurred in filter grown cells exposed to 40 mM of hydrogen peroxide after 1 hr. Filter-grown Caco-2 cells were less sensitive to hydrogen peroxide than the nonfilter-grown ones. PMID- 17849274 TI - Acute depletion and recovery of peritoneal B-1 lymphocytes in BALB/c mice after a single injection of mercury chloride. AB - The acute toxicity of mercury (Hg) to B cells was studied in the peritoneal cavity of BALB/c mice, a coelomic space where both B-1 and B-2 subsets of B lymphocytes are present. Up to 24 hr after a single in situ Hg injection, the peritoneal cavity became virtually devoid of lymphocytes, particularly of the B-1 subset. Lymphocyte depletion was more severe for B than T cells. This depletion was associated with partial lymphocyte activation (CD69(+)) at 6 hr of treatment and it was due to apoptosis rather than to necrosis. Partial recovery of both B and T cells was observed in the peritoneal cavity 48 hr after the Hg injection. The phenomenon was followed by a second decrease in peritoneal lymphocytes 72 hr after Hg. Neutrophils that entered the peritoneal cavity because of the Hg injection were resistant to apoptosis. No significant changes in lymphocyte number or subpopulation were found in the spleen and thymus of the mice up to 72 hr after the Hg treatment. We concluded that B lymphocytes were severely affected by the toxic effects of Hg. Our data suggest that Hg-induced unbalance in the repertoire of B cells, of the B-1 subset in particular, may result later in the secretion of the high titres of pathogenic autoantibodies that are found in the Hg-induced lupus disorder of BALB/c mice. PMID- 17849275 TI - Effects of isoflavones and soybeans fermented with Bacillus subtilis on lipopolysaccharide-induced production of tumor necrosis factor-alpha and fibrinolysis in vivo. AB - The effects of isoflavones and of a derivative of soybeans fermented with Bacillus subtilis, designated Nattoesse, on the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-alpha) and fibrinolysis were investigated in vivo. The dietary supplement Nattoesse contains several isoflavones. Therefore, we examined the effects of individual isoflavones (daidzein, daidzin, genistein, and genistin) on the LPS-induced production of TNF alpha. Intraperitoneal injections of daidzein, daidzin, and genistin (but not of genistein before a challenge with LPS) resulted in significant depression of serum levels of TNF-alpha in mice. Daidzein had the strongest activity in this assay. Oral administration of daidzein to mice also had a significant suppressive effect, as compared with that of the Citrus flavanone naringin. In galactosamine sensitized mice, by contrast, the suppression of LPS-induced lethal shock by daidzein was very weak. Nattoesse did not inhibit the production of TNF-alpha nor did it prevent lethal shock. However, oral administration of Nattoesse to mice significantly suppressed LPS-induced increases in scores of the fibrin degradation product, and the effect was both dose- and time-dependent. Thus, it appears that Nattoesse has fibrinolytic activity during LPS-induced circulatory failure. PMID- 17849276 TI - Airway remodeling in the smoke exposed guinea pig model. AB - Although small airway remodeling (SAR) leading to airflow obstruction is a common consequence of human cigarette smoking, the airways have been largely ignored in animal models of chronic obstructive pulmonary disease (COPD). We examined lung structure in a guinea pig model of chronic cigarette smoke exposure to ascertain whether smoke induced SAR, and to evaluate how these anatomic lesions correlate with physiologic changes. We used tissue from guinea pigs exposed to cigarette smoke or air for 6 mo. Pulmonary function tests were performed, and histologic sections were prepared. Airspace size (Lm) and changes in the structure of the small airways were evaluated by morphometric analysis. Chronic smoke exposure was associated with increased airway wall thickness and increased amounts of thick collagen fibers in the walls of the small airways, as well as with increased Lm. The increase in thick collagen fibers related negatively to peak expiratory volume (PEF) and the ratio of forced expiratory volume in 1 s to forced ventilatory capacity (FEV(0.1)/FVC), and positively to airway resistance. Physiologic lung volumes were predicted by airspace size, but residual volume (RV) and total lung capacity (TLC) also were related to airway wall thickness. Amounts of smooth muscle were not changed and did not predict any physiologic abnormalities. We conclude that cigarette smoke exposure results in SAR in the guinea pig, alterations that are reflected in increased airways resistance with diminished airflow and air trapping, mimicking human disease. This model should prove useful in further investigations into the mechanisms of airway remodeling. PMID- 17849277 TI - Mathematical analysis of particle deposition in human lungs: an improved single path transport model. AB - A dynamic single-path mathematical model was developed that is capable of analyzing detailed deposition patterns of inhaled particles in human lungs. Weibel's symmetric lung morphology was adopted as the basic lung structure, and detailed transport processes were evaluated numerically using the fully implicit procedure. Deposition efficiencies by specific mechanisms were individually examined for accuracy and new empirical formulas were incorporated whenever appropriate. Deposition in the alveolar region was divided into deposition fractions in the alveolar duct and alveoli, considering active transport processes between the two regions. The deposition fractions were obtained for each airway generation, serial lung volumetric compartments, and conventional three-compartment anatomic lung regions. In addition, the surface dose and cumulative deposition with time were analyzed. The results showed excellent agreement with available experimental data. The present model provides an improvement from the previously reported models and can be used as a tool in assessing internal dose of inhaled particles under various inhalation conditions. PMID- 17849278 TI - Basal gene expression in male and female Sprague-Dawley rat nasal respiratory and olfactory epithelium. AB - The nasal epithelium is an important target site for chemically induced toxicity and carcinogenicity. Experimental studies show that site-specific lesions can arise within the nasal respiratory or olfactory epithelium following the inhalation of certain chemicals. Moreover, gender differences in epithelial response are also reported. To better understand and predict gender differences in response of the nasal epithelium to inhaled xenobiotics, gene expression profiles from naive male and female Sprague-Dawley rats were constructed. Epithelial cells were manually collected from the nasal septum, naso- and maxillo turbinates, and ethmoid turbinates of nine male and nine female rats. Gene expression analysis was performed using the Affymetrix Rat Genome 430 2.0 microarray. Surprisingly, there were few gender differences in gene expression. Gene ontology enrichment analysis identified several functional categories, including xenobiotic metabolism, cell cycle, apoptosis, and ion channel/transport, with significantly different expression between tissue types. These baseline data will contribute to our understanding of the normal physiology and selectivity of the nasal epithelial cells' response to inhaled environmental toxicants. PMID- 17849279 TI - Pulmonary toxicity screening studies in male rats with M5 respirable fibers and particulates. AB - M5 fiber is a high-strength, high-performance organic fiber type that is a rigid rod material and composed of heterocyclic polymer fibers of type PIPD. The aim of this study was to evaluate the acute lung toxicity of intratracheally instilled M5 respirable fibers and particulates in rats. Using a pulmonary bioassay and bridging methodology, the acute lung toxicity of intratracheally instilled M5 particulates and that of its fibers were compared with a positive control particle type, quartz, as well as a negative control particle type, carbonyl iron particles. Moreover, the results of these instillation studies were bridged with data previously generated from inhalation studies with quartz and carbonyl iron particles, using the quartz and iron particles as the inhalation/instillation bridge material. For the bioassay experimental design, in the bronchoalveolar lavage studies, the lungs of rats were intratracheally instilled with 0.5 or 0.75 mg/kg of M5 particulate or 1 or 5 mg/kg of the following control or particle types: (1) M5 long fiber preparation, (2) silica-quartz particles, and (3) carbonyl iron particles. Phosphate-buffered saline (PBS)-instilled rats served as additional controls. Following exposures, the lungs of PBS and particle-exposed rats were assessed using bronchoalveolar lavage (BAL) fluid biomarkers, cell proliferation methods, and histopathological evaluation of lung tissue at 24 h, 1 wk, 1 mo and 3 mo post instillation exposure. The bronchoalveolar lavage results demonstrated that lung exposures to quartz particles, at both concentrations but particularly at the higher dose, produced significant increases vs. controls in pulmonary inflammation and cytotoxicity indices. Exposures to M5 particulate and M5 long fiber preparation produced transient inflammatory and cell injury effects at 24 h postexposure (pe) as well as at 24 h and 1 wk pe, respectively, but these effects were not sustained when compared to quartz-silica effects. Exposures to carbonyl iron particles and PBS resulted in only minor short-term and reversible lung inflammation, likely related to the effects of the instillation procedure. Histopathological analyses of lung tissues revealed that pulmonary exposures to M5 particulate and in particular, the M5 long fiber preparation in rats produced some inflammatory responses, observed up to 1 wk postexposure. These responses were often associated with the presence of M5 long fiber in the airways or in the proximal alveolar regions but appeared to be reversible at 1 and 3 mo postexposure. In contrast, pulmonary exposures to silica-quartz particles in rats produced a dose-dependent lung inflammatory response characterized by neutrophils and foamy (lipid-containing) alveolar macrophage accumulation and evidence of early lung tissue thickening consistent with the development of pulmonary fibrosis. Based on our results, we conclude the following: (1) It was very difficult to produce M5 fibers into a respirable fibrous form; these findings suggest that aerosol exposure concentrations of respirable fibrous M5 in the workplace are likely to be rather low. (2) The particulate and long fiber preparations of M5 that were tested produced a moderate amount of pulmonary inflammatory activity, more active than our negative control, carbonyl iron particles, but substantially less active in terms of inflammation, cytotoxicity, and fibrogenic effects than the positive control particle type, silica-quartz particles. Thus, based on the results of this study, we would expect that inhaled M5 respirable fibers have a low risk potential for producing adverse pulmonary effects. PMID- 17849280 TI - Comparison of high MRI T1 signals with manganese concentration in brains of cynomolgus monkeys after 8 months of stainless steel welding-fume exposure. AB - Several pharmacokinetic studies on inhalation exposure to manganese (Mn) have already demonstrated that Mn readily accumulates in the olfactory and brain regions. However, a shortening of the magnetic resonance imaging (MRI) T1 relaxation time or high T1 signal intensity in specific sites of the brain, including the globus pallidus and subcortical frontal white matter, as indicative of tissue manganese accumulation has not yet been clearly established for certain durations of known doses of welding-fume exposure in experimental animals. Accordingly, to investigate the movement of manganese after welding-fume exposure, six cynomolgus monkeys were acclimated and assigned to three dose groups: unexposed, low dose (31 mg/m(3) total suspended particulate [TSP], 0.9 mg/m(3) of Mn), and high dose (62 mg/m(3) TSP, 1.95 mg/m(3) of Mn) of total suspended particulate. The primates were exposed to manual metal arc stainless steel (MMA-SS) welding fumes for 2 h per day in an inhalation chamber system equipped with an automatic fume generator. Magnetic resonance imaging (MRI) studies were conducted before the initiation of exposure and thereafter every month. The tissue Mn concentrations were then measured after a plateau was reached regarding the shortening of the MRI T1 relaxation time. A dose-dependent increase in the Mn concentration was found in the lungs, while noticeable increases in the Mn concentrations were found in certain tissues, such as the liver, kidneys, and testes. Slight increases in the Mn concentrations were found in the caudate, putamen, frontal lobe, and substantia nigra, while a dose dependent noticeable increase was only found in the globus pallidus. Therefore, the present results indicated that a shortening of the MRI T1 relaxation time corresponded well with the Mn concentration in the globus pallidus after prolonged welding-fume exposure. PMID- 17849281 TI - Effects of concentrated ambient particles on heart rate, blood pressure, and cardiac contractility in spontaneously hypertensive rats during a dust storm event. AB - Epidemiological studies have suggested that cardiovascular mortality and morbidity increased during Asian dust events. The findings were still inconclusive though. We have shown an increased pulmonary toxicity in diseased animals during a dust storm event. However, the toxicity nature of dust storm particles remains unclear. It is our objective in this study to further investigate the cardiovascular effects of concentrated PM(2.5) on spontaneously hypertensive rats during the same dust storm event. Four spontaneously hypertensive rats were implanted with radiotelemetry transmitters at the age of 10 wk. Baseline heart rate, mean blood pressure, and cardiac contractility (measured as QA interval, QAI) data were collected 4 wk before. Exposure group received concentrated ambient particles inhalation for 6 h during a dust storm event, while the control group received room air inhalation at the same time. Self-control data were collected 4 wk after the event during the same clock hours while there was no dust storm. Gravimetric analysis showed a particle mass concentration of 315.55 microg/m(3) during the 6 h of exposure. A linear mixed effects model revealed sigmoid increases in heart rate (to a maximum of 93.8 +/- 18.8 bpm) and mean blood pressure (to a maximum of 14.8 +/- 5.4 mm Hg), and a sigmoid decrease of QAI (to a maximum of - 3.5 +/- 1.5 ms) during the exposure after an initial incubation period. We conclude that concentrated dust storm particles, which are different from products of automobile combustion process, may cause adverse cardiovascular effects on diseased animals. PMID- 17849282 TI - The vasodilator effect and its mechanism of sulfur dioxide-derivatives on isolated aortic rings of rats. AB - The vasodilator effect of exogenous sulfur dioxide (SO(2)) derivatives (mixture of sodium bisulfite and sodium sulfite, 3:1 M/M in neutral solution) on rat vascular system was studied in order to explore the mechanism of blood pressure lowered by SO(2) and its derivatives. Isolated rat aortic rings were perfused in bath tubes containing various chemicals and their tensions were recorded. The results showed: (1) The SO(2) derivatives could relax isolated aorta precontracted by norepinephrine (NE) or potassium chloride (KCl) in a dose dependent manner. (2) This vasodilator effect was attenuated after preincubation with indomethacin, but was not affected by N-L-nitro-arginine, methylene blue, and propranolol, and was independent of the aorta endothelium. (3) The vasoconstriction responses induced by NE, KCl, or Ca(2+) were antagonized by SO(2) derivatives in a noncompetitive manner. (4) The vasoconstrictions of two components (initial fast vasoconstriction induced by intracellular Ca(2+) release and sustained vasoconstriction evoked by extracellular Ca(2+) influx) were also inhibited by SO(2) derivatives. These results led to the conclusions: The SO(2) derivatives could cause vasorelaxation by a direct role of the chemicals on aortic smooth muscle cells. It was not dependent on vascular endothelium and was independent of nitric oxide (NO). It is suggested that SO(2) and its derivatives might be also vasoactive substances that modulate changes of blood pressure, like other gasotransmitters. The vasorelaxation might be related to the inhibition effects of SO(2) derivatives on Ca(2+) entry through both potential-dependent calcium channels and receptor-operating calcium channels, and also to the inhibition of intracellular Ca(2+) release. The vasorelaxation was at partly related to the increase of prostacyclin (PGI(2)) induced by SO(2) derivatives. PMID- 17849283 TI - Issues revolving round the regulation of reproductively related genes in Drosophila. PMID- 17849284 TI - A genetic modifier screen identifies multiple genes that interact with Drosophila Rap/Fzr and suggests novel cellular roles. AB - In the developing Drosophila eye, Rap/Fzr plays a critical role in neural patterning by regulating the timely exit of precursor cells. Rap/Fzr (Retina aberrant in pattern/Fizzy related) is an activator of the E3 Ubiquitin ligase, the APC (Anaphase Promoting Complex-cyclosome) that facilitates the stage specific proteolytic destruction of mitotic regulators, such as cyclins and cyclin-dependent kinases. To identify novel functional roles of Rap/Fzr, we conducted an F(1) genetic modifier screen to identify genes which interact with the partial-loss-function mutations in rap/fzr. We screened 2741 single P element, lethal insertion lines and piggyBac lines on the second and third chromosome for dominant enhancers and suppressors of the rough eye phenotype of rap/fzr. From this screen, we have identified 40 genes that exhibit dosage sensitive interactions with rap/fzr; of these, 31 have previously characterized cellular functions. Seven of the modifiers identified in this study are regulators of cell cycle progression with previously known interactions with rap/fzr. Among the remaining modifiers, 27 encode proteins involved in other cellular functions not directly related to cell-cycle progression. The newly identified variants fall into at least three groups based on their previously known cellular functions: transcriptional regulation, regulated proteolysis, and signal transduction. These results suggest that, in addition to cell cycle regulation, rap/fzr regulates ubiquitin-ligase-mediated protein degradation in the developing nervous system as well as in other tissues. PMID- 17849285 TI - Novel protein-truncating mutations in the ASPM gene in families with autosomal recessive primary microcephaly. AB - Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that causes reduction in brain size. Individuals affected with the disorder show a small but architecturally normal cerebral cortex and are associated with mental retardation of mild-to severe form. MCPH is genetically heterogeneous with six loci, and four genes have been identified so far. Homozygous mutations in the ASPM gene, located at MCPH5 locus on chromosome 1q31, are the most common cause of MCPH particularly in the Pakistani population. In the present study, we have ascertained ten Pakistani and one Kashmiri family with primary microcephaly. We screened for potential mutations of the ASPM gene in seven consanguineous families (six Pakistani and one Kashmiri) linked to MCPH5 locus. Two previously reported (8508delGA, W1326X) and four novel sequence variants (Y1712X, I1717X, Y3353X, R3244X) were detected and all were predicted to be protein truncating. The degree of mental retardation in the affected individuals of the seven families varied from mild to moderate, and was not dependent on the location of mutations in the ASPM gene. PMID- 17849286 TI - Biotechnological approach to the synthesis of 9alpha-hydroxylated steroids. AB - The steroid 9alpha-hydroxylase gene has been cloned from Mycobacterium smegmatis into Escherichia coli BL21. Progesterone added to bioreactors was subjected to in vivo transformation into 9alpha-hydroxyprogesterone. In 7 days, 43.6 mg 9alpha hydroxyprogesterone was formed from 53.8 mg/L progesterone. The enzyme also has shown evidence of processing 4-androstene-3,17-dione in vivo. An extensive analytical method development, including LLE, HPLC-DAD, MS, and NMR was performed to verify the product and to enable a quantitative analysis. Protocols for analytical and preparative separation have been developed, using binaphtol as internal standard. Both the growth pattern and the bioconversion rate were unaffected by the presence of binaphtol in the bioreactor. The enzyme was purified by immobilised metal affinity and ion exchange chromatography, resulting in low in vitro activity. PMID- 17849287 TI - Isolation of RNA from polysaccharide-rich seeds. AB - Commonly, RNA isolation is the initial step in the study of gene expression analysis and also in the utilization of genes for genetic improvement. However, the recovery of large amounts of RNA with high quality is a difficult process, especially in tissues containing enhanced levels of polysaccharides and other secondary metabolites. Since several procedures for RNA isolation from polysaccharides rich plant tissues have been resulting in poor yields, an effective new protocol is essential for RNA isolation and further analysis. Here, we describe a novel modified technique for isolating total RNA from maturing grains. As a model, we utilized little finger millets, important food staples, which correspond to short duration crops cultivated in varied agro climatic conditions. After isolation, the total RNA was resolved on a denaturing agarose gel, showing more sharp bands of 28S, 18S, and 5S with no degradation. Therefore, the RNA concentration (higher than 1.80) was calculated by spectrophotometry, indicating that RNA is concentrated. Finally, RT-PCR and Northern hybridization confirmed high RNA quality. PMID- 17849288 TI - Improving the purification of NAD+-dependent formate dehydrogenase from Candida methylica. AB - The Candida methylica (cm) recombinant wild type formate dehydrogenase (FDH) gene has been cloned into the pQE-2 TAGZyme expression vector and the 6xHis-tagged FDH gene has been overexpressed in JM105 cells to purify the FDH protein more efficiently, by the use of exopeptidases, TAGZyme Purification System, which has allowed the complete removal of the small N-terminal His-tag. After the purification procedure, 1.2 mg/mL cmFDH protein of >95% purity was obtained. The kinetic parameters of cmFDH have been determined by observing the oxidation of the nicotinamide coenzyme at 340 nm. The results have also been compared to the yield of standard vs. affinity purification of FDH. PMID- 17849289 TI - Sanionins: anti-inflammatory and antibacterial agents with weak cytotoxicity from the Antarctic moss Sanionia georgico-uncinata. AB - Sanionins A (1) and B (2) were isolated from the moss Sanionia georgico-uncinata, collected on the Antarctic Livingston Island. The compounds 1 and 2 were purified by solvent extraction, silica gel column chromatography, and preparative HPLC, consecutively. The structures of the both compounds were elucidated by 1D and 2D NMR experiments and mass spectrometric investigations. These compounds showed activity against important Gram-positive pathogens, such as mycobacteria, multiresistant staphylococci, and vancomycin resistant enterococci. This activity is combined with antiinflammatoric activity and low cytotoxicity. PMID- 17849290 TI - Analysis of secreted protein profile and enzymatic activities from Corynebacterium diphtheriae and Bordetella pertussis on production batch media using peptide quenched fluorescent substrates. AB - Proteases were identified and characterized from the culture supernatant of the C. diphtheriae and B. pertussis bacteria. The proteases were secreted in the media and detected at the end of the exponential growth phase. Activity was detected in some fluorescent substrates, based on selected protein sequences such as insuline beta-chain, bradykinin, and synaptobrevin. The proteases were purified by means of gel filtration chromatography. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the purified proteins indicated, for the main secreted proteins, an estimated molecular mass of 30 kDa in C. diphtheriae and 69 kDa in B. pertussis culture media. The proteases were stable and presented enzymatic activity at 37 degrees C. These proteases were not related to the main toxic compounds described in these two bacteria, but could represent good markers for the fermentation process when the enzyme activity was measured with the fluorescent substrates. PMID- 17849291 TI - Comparison of rapid DNA extraction methods applied to PCR identification of medicinal mushroom Ganoderma spp. AB - Four different DNA extraction methods were used to extract genomic DNA of the medicinal mushroom Lingzhi from its developing stage materials, such as mycelium, dry fruiting body, or sliced and spore powder or sporoderm-broken spore powder. The DNA samples were analyzed using agarose gel electrophoresis, UV spectrophotometer, and PCR amplification. According to the average yields and purity of DNA, high salt concentrations and low pH methods were the best for DNA extraction. The mycelia and sporoderm-broken spore powder yielded higher and purer DNA. The method developed could effectively eliminate the influence of the secondary metabolites to DNA extraction. The DNA samples extracted from the developed method could be successfully used for PCR applications. PMID- 17849292 TI - An Efficient one-pot Biginelli condensation of aliphatic aldehydes catalyzed by zinc bromide under solvent-free conditions. AB - Zinc bromide catalyzes the three component condensation reaction of an aldehyde, urea, and beta-ketoester or beta-diketone under solvent-free conditions to afford the corresponding dihydropyrimidinones (DHPMs) with moderate to high yields in short reaction time. The present method is very effective for the Biginelli condensation of aliphatic aldehydes. PMID- 17849294 TI - The application of thermal methods for determining chemical composition of carbonaceous aerosols: a review. AB - Thermal methods of various forms have been used to quantify carbonaceous materials. Thermal/optical carbon analysis provides measurements of organic and elemental carbon concentrations as well as fractions evolving at specific temperatures in ambient and source aerosols. Detection of thermally desorbed organic compounds with thermal desorption-gas chromatography/mass spectrometry (TD-GC/MS) identifies and quantifies over 100 individual organic compounds in particulate matter (PM) samples. The resulting mass spectra contain information that is consistent among, but different between, source emissions even in the absence of association with specific organic compounds. TD-GC/MS is a demonstrated alternative to solvent extraction for many organic compounds and can be applied to samples from existing networks. It is amenable to field-deployable instruments capable of measuring organic aerosol composition in near real-time. In this review, thermal stability of organic compounds is related to chemical structures, providing a basis for understanding thermochemical properties of carbonaceous aerosols. Recent advances in thermal methods applied to determine aerosol chemical compositions are summarized and their potential for uncovering aerosol chemistry are evaluated. Current limitations and future research needs of the thermal methods are included. PMID- 17849295 TI - Adsorption kinetics, thermodynamics and desorption of natural dissolved organic matter by multiwalled carbon nanotubes. AB - Multiwalled carbon nanotubes (CNTs) were thermally treated and were employed as adsorbents to study their adsorption kinetics and thermodynamics of natural dissolved organic matter (NDOM) from aqueous solutions. The adsorption kinetics follows the first-order rate law while the adsorption thermodynamics indicates the exothermic and spontaneous nature. A comparative study on the adsorption/desorption properties of NDOM between CNTs and granular activated carbon (GAC) was also conducted and revealed that the CNTs possess more NDOM adsorption capacities and show less weight loss through 10 cycles of water treatment and reactivation than the GAC. This suggests that the CNTs are promising NDOM adsorbents for preventing the microbiological degradation of drinking water quality as well as the formation of disinfection by products in water treatment. PMID- 17849296 TI - Lipid biomarkers profile--presence of coprostanol: recent sediments from Rodrigo de Freitas Lagoon-Rio de Janeiro, Brazil. AB - Coprostanol (contribution characteristic from anthropogenic pollution) and other lipid biomarkers (sterols, fatty alcohols and fatty acids) were identified and quantified in recent sediment extracts from Rodrigo de Freitas Lagoon, a touristy spot of Rio de Janeiro-Brazil, using gas chromatography with mass selective detector (GC-MSD). The determination of lipid biomarkers profile indicates an autochthonous biogenic contribution due to the presence of phytoplankton, zooplankton, bacteria and dinoflagellates. The allochthonous biogenic contribution was confirmed by detection of biomarkers from higher plants in the sediments due to the influence of the Atlantic Forest inserted in the studied region. The concentration of the studied compounds varied from 5.53 to 216.47 microg.g(-1) for sterols, 0.47 to 5.35 microg.g(-1) for fatty alcohols, 20.15 to 66.22 microg.g(-1) for fatty acids and 0.08 to 3.98 microg.g(-1) for coprostanol. The presence of coprostanol was attributed to illegal untreated sewage discharge in the pluvial collector which ends up in the Lagoon. PMID- 17849297 TI - Comparison of HSPF and SWAT models performance for runoff and sediment yield prediction. AB - A watershed model can be used to better understand the relationship between land use activities and hydrologic/water quality processes that occur within a watershed. The physically based, distributed parameter model (SWAT) and a conceptual, lumped parameter model (HSPF), were selected and their performance were compared in simulating runoff and sediment yields from the Polecat Creek watershed in Virginia, which is 12,048 ha in size. A monitoring project was conducted in Polecat Creek watershed during the period of October 1994 to June 2000. The observed data (stream flow and sediment yield) from the monitoring project was used in the calibration/validations of the models. The period of September 1996 to June 2000 was used for the calibration and October 1994 to December 1995 was used for the validation of the models. The outputs from the models were compared to the observed data at several sub-watershed outlets and at the watershed outlet of the Polecat Creek watershed. The results indicated that both models were generally able to simulate stream flow and sediment yields well during both the calibration/validation periods. For annual and monthly loads, HSPF simulated hydrologic and sediment yield more accurately than SWAT at all monitoring sites within the watershed. The results of this study indicate that both the SWAT and HSPF watershed models performed sufficiently well in the simulation of stream flow and sediment yield with HSPF performing moderately better than SWAT for simulation time-steps greater than a month. PMID- 17849298 TI - Effects of tetracycline on antibiotic resistance and removal of fecal indicator bacteria in aerated and unaerated leachfield mesocosms. AB - Antibiotics can be present in low concentrations in domestic wastewater, but little is known about their effect on bacteria in onsite wastewater treatment systems. Mesocosms, consisting of soil-filled lysimeters representing the leachfield of a septic system under aerated (AIR) and unaerated (LEACH) conditions, were used to study the effects of tetracycline addition (5 mg L(-1)) to septic tank effluent on tetracycline resistance in the fecal indicator bacteria Escherichia coli and fecal streptococci, and on their removal. The mesocosms were dosed with antibiotic for 10 days, and effects monitored for 52 days. The fraction of resistant bacteria in mesocosm drainage water relative to that in septic tank effluent, GammaRes, for E. coli ranged from 0 to 0.66 in the AIR treatment and from 0 to 3.32 in the LEACH treatment. For fecal streptococci, GammaRes ranged from 0 to 0.41 and from 0.63 to 1.06 in the AIR and LEACH treatments, respectively. No significant differences in antibiotic resistance of fecal indicator bacteria were observed among sampling dates in soil or water from either treatment. Tetracycline had no significant effect on removal of fecal indicator bacteria, which ranged from 99.9 to 100% for E. coli and from 95.9 to 100% for fecal streptococci. Our results suggest that short-term addition of tetracycline at environmentally-relevant concentrations is likely to have minimal consequences on pathogen removal from wastewater and development of antibiotic resistance among pathogenic bacteria in leachfield soil. PMID- 17849299 TI - Inactivation of Pseudomonas aeruginosa and Aeromonas hydrophila by silver in tap water. AB - This study was conducted to assess the efficacy of silver as a secondary disinfectant to replace or reduce the level of chlorine utilized in water distribution systems. Pseudomonas aeruginosa and Aeromonas hydrophila are opportunistic pathogens present in drinking water and have been associated with waterborne disease. After 8 hours of exposure to 100 microg/L of silver, there was a >6-log10 reduction in P. aeruginosa in tap water at room temperature at pH7 and a 5.55-log10 reduction in the presence of 3 mg/L humic acid. Similar reductions were observed at pH9. At 4 degrees C, reductions greater than 4-log10 were observed after 24 hours. For A. hydrophila, a >6-log10 reduction occurred at both pH7 and pH9 within nine hours. The World Health Organization has determined that this amount of silver could be used for water disinfection without health risks. Furthermore, silver shows promise as a secondary disinfectant, even in the presence of organic matter in concentrations that would reduce the effectiveness of free chlorine. PMID- 17849300 TI - Modeling and fixed bed column adsorption of As(V) on laterite soil. AB - Laterite soil, an abundant locally available natural adsorbent, has been evaluated for As(V) removal from aqueous solutions in column mode operation. The column studies were conducted using columns of 10, 20, 30 cm bed depth with 2 cm internal diameter. Initial As(V) concentration was 0.5 mg/L and flow rate was 7.75 mL/min. Bohart and Adams sorption model was employed for the determination of different parameters like height of exchange zone, adsorption rate, time required for exchange zone to move, and the adsorption capacity. Effect of flow rate and initial concentration was studied. The adsorption capacity of the laterite soil for 0.5 mg/L of As(V) was found to be 62.32 mg/L, and the adsorption rate constant was 1.0911 L/mg h for the minimum bed depth of 8.47 cm. The column was designed by the BDST model. Freundlich isotherm model was used to compare the theoretical and experimental breakthrough profile in the dynamic process. The bed saturation obtained was 36-80%. Regeneration of the exhausted column was possible with 1M NaOH. PMID- 17849301 TI - A method to characterize the greenness of solvents used in pharmaceutical manufacture. AB - This paper describes the development of a method to calculate the overall "greenness" of a pharmaceutical process that uses multiple solvents. This calculation is made by taking into account various environmental parameters and determining an overall greenness index. Through this method a scientist or engineer can effectively determine alternative, "greener" solvents or processes based on the use of a solvent database and greenness score. The objective is to develop a means to improve the process of drug development through solvent replacement/reduction. A solvent selection table, using a common spreadsheet software routine, was developed for the purpose of allowing a user to compare the greenness between two different process routes. This table includes over 60 solvents and associated chemicals common in the pharmaceutical and chemical industries. The comparison was made possible by the creation of a user-defined, weighted-solvent, greenness index that is an overall weighted factor taking into consideration solvent type, quantity used, and environmental impact. A given process or solvent receives an index ranking based on a variety of environmental and health parameters. The index values, along with the mass of solvents used in the given process, are used to compute the index, which allows for a quick and easy quantitative environmental comparison between two potential process routes. PMID- 17849302 TI - Comprehensive two-dimensional GC (GCxGC) qMS analysis of tetrachloronaphthalenes in Halowax formulations. AB - A combination of non-polar and shape selective columns in a comprehensive two dimensional GC (GCxGC) system consisting of DB-5MS and LC-50 as the 1st and 2nd dimension columns was used to separate 22 tetrachloronaphthalene isomers. These columns enabled separation of all possible isomers of tetraCN found in the technical chloronaphthalene Halowax formulations into 18 peaks covering 15 single separated isomers and 7 co-eluting in triplicate (1,2,4,6-/1,2,4,7-/1,2,5,7 tetraCN; nos. 33/34/37) and in pairs (1,2,3,7-/1,2,4,5-tetraCN; nos. 30/32 as well as 1,3,5,8-/1,3,6,8-tetraCN; nos. 43/45). Twelve isomers of tetraCN resolved as single compounds by the GC x GC system used were found in Halowax 1001, 1013, 1014 and 1099 as well as in Equi-Halowax mixture. Three other tetraCNs that could be also resolved as single compounds were not detected in these materials, while the remaining 7 tetraCNs, which co-eluted, waits a further separation. The majority of constituents of the tetraCN homologue group of the Halowax formulations are isomers such as 1,4,5,8- (no. 46), 1,2,5,8- (no. 38), 1,2,4,8 tetraCN (no. 35), co-eluting 1,3,5,8-tetraCN (no. 43 in a pair nos. 43/45) and also co-eluting 1,2,4,6-/1,2,4,7-/1,2,5,7-tetraCN (nos. 33/34/37). The less abundant by amongst of tetraCNs in these mixtures are 1,4,6,7- (no. 47) and 1,3,5,7-tetraCN (no. 42). The remaining seven isomers, i.e., 1,2,3,4- (no. 27), 1,2,3,5- (no. 28), 1,2,3,6- (no. 29), 1,2,5,6- (no. 36), 1,2,6,7- (no. 39), 1,2,6,8- (no. 40) and 1,2,7,8-tetraCN (no. 41) are usually minor by quantity, while 1,2,3,7-/1,2,4,5-tetraCN (nos. 30/32) are also minor, or one of them is absent. Three tetraCNs not found in the Halowax formulations are isomers such as 1,2,3,8-tetraCN (no. 31), 1,3,6,7-tetraCN (no. 44) and 2,3,6,7-tetraCN (no. 48). PMID- 17849303 TI - Selected elements in fly agaric Amanita muscaria. AB - Concentrations of Ag, Al, Ba, Ca, Cd, Co, Cu, Cr, Cs, Fe, Ga, Hg, K, Mg, Mn, Mo, Na, Pb, Rb, Se, Sb, Sr, V, Tl and Zn have been determined in the whole fruiting bodies, as well as separately in caps and stalks, of fly agaric collected from three geographically distant sites in northern part of Poland. The elements were determined using ICP-MS, ICP-OES, HG-AAS and CV-AAS, respectively. For elements such as Al, Ba, Cr, Fe, Ga, Mo, Mn, Pb, Sb, Sr, Tl, and V concentrations were similar in the caps and stalks, respectively, and for K, Zn, Ag, Ca, Cd, Cu, Hg, Mg, Rb and Se were greater in the caps, while for Co, Cs and Na in the stalks. For Ag, Al, Ba, Ca, Cd, Co, Cr, Cs, Fe, Ga, Hg, Mn, Mo, Pb, Rb, Sb, Sr, Tl and V concentration in the caps showed spatial variations (P<0.05), while for Cu, K, Mg, Na, Se and Zn was independent of the site. The elements such as K with median or mean in the caps between 37,000 and 43,000 microg/g.dm and Mg with 920 and 1,100 microg/g dm were most abundant. Next, within median values range from approximately 100 to 500 microg/g dm were such as Ca, Fe and Al, and in descending order they followed by Rb (100-400 microg/g dm); V, Na, Zn (50-200 microg/g dm); Cu, Mn (10-50 microg/g dm); Cd (10-20 microg/g dm); Se (5 microg/g dm); Ba (<1-3); Cr, Ag, Pb, Sr (<1-2 microg/g dm); Cs, Co, Hg (<1-1 microg/g dm); Ga (<0.5), Sb, Mo and Tl (<0.1 microg/g dm). PMID- 17849304 TI - Mercury and its bioconcentration factors in fly agaric (Amanita muscaria) from spatially distant sites in Poland. AB - Total mercury content has been determined in the fruiting bodies of fly agaric (Amanita muscaria) and topsoil layer (0-10 cm) collected from 14 spatially distant sites across Poland. Mercury was measured by cold-vapor atomic absorption spectroscopy (CV-AAS) after nitric acid (mushrooms) or nitric acid and sulfuric acid (soil) digestion of the samples. The caps, depending on the site, contained total mercury at mean concentrations from 0.24+/-0.13 to 1.4+/-0.6 microg/g dm (median 0.19-1.4 microg/g dm), and stalks from 0.18+/-0.06 to 0.71+/-0.26 microg/g dm (median 0.18-0.67 microg/g dm). An overall-mean the total mercury content for 204 caps and stalks was, respectively, 0.73+/-0.55 (0.05-3.3 microg/g dm) and 0.43+/-0.33 (0.09-2.3 microg/g dm). PMID- 17849305 TI - Natural radionuclides measurements and total dose indicative evaluation in drinking waters of an Italian central region. AB - A study of radioactivity content in drinking waters collected in some areas of geological interest in an Italian central region was performed to check the compliance with recent European regulations. Gross alpha and beta activities, 226Ra, 238U, 234U, 210Po and 3H concentrations were measured. Gross alpha and beta, 226Ra and 3H activities were determined using an ultra-low-level scintillation counter, 238U, 234U and 210Po by alpha spectrometry after radiochemical separation. Recommended WHO guideline activity concentrations for drinking water were exceeded in 6 cases for gross alpha activity and were not exceeded in any case for gross beta activity. Tritium concentration was always lower than MDA (6.75 Bq L(-1)); the concentrations (mBq L(-1)) of 226Ra, 238U, 234U and 210Po ranged from <1.80 to 23.00, from 1.20 to 140.00, from 1.60 to 120.00 and from 0.25 to 5.90, respectively. Due to the importance of the water in human diet, the doses were calculated for children and adults using the dose coefficient factors reported by EC Directive 96/29 EURATOM and annual water intake; all samples furnished a dose lower the reference level for drinking water (0.1 mSv y(-1)). PMID- 17849306 TI - Characterization of microbial communities in a pilot-scale constructed wetland using PLFA and PCR-DGGE analyses. AB - Phospholipid fatty acid (PLFA) analysis and 16S ribosomal DNA polymerase chain reaction amplification-denaturing gradient gel electrophoresis (PCR-DGGE) were used to determine microbial communities and predominant microbial populations in water samples collected from a pilot-scale constructed wetland system. This pilot scale constructed wetland system consists of three types: subsurface-flow (SSF), surface-flow (SF) and a floating aquatic plant (FAP) system. Analysis of PLFA profiles indicated primarily eukaryotic organisms, including fungi, protozoa, and diatoms were observed in all three wetland systems. Biomarkers for Gram-negative bacteria were also detected in all samples analyzed while low proportions of biomarkers for Gram-positive bacteria were observed. Biomass content (total PFLA/sample) was highest in water samples collected from both SF and FAP system while highest metabolic activity was observed in FAP system. This is consistent with the observed highest metal removal rate in FAP system. Sequence analysis of the predominant PCR-DGGE DNA fragments showed 0.92 to 0.99 similarity indices to Beta-proteobacteria, Flavobacterium sp. GOBB3-206, Flexibacter-Cytophaga Bacteroides group, and Gram-positive bacteria. Results suggest diverse microbial communities including microorganisms that may significantly contribute to biogeochemical elemental cycles. PMID- 17849307 TI - Evaluation of TENORMs field measurement with actual activity concentration in contaminated soil matrices. AB - The occurrence of technologically enhanced naturally occurring radioactive materials (TENORMs) concentrated through anthropogenic processes in contaminated soils at oil and gas facilities represent one of the most challenging issues facing the Canadian and US oil and gas industry today. Natural occurring radioactivity materials (NORMs) field survey techniques are widely used as a rapid and cost-effective method for ascertaining NORMs risks associated with contaminated soils and waste matrices as well other components comprising the environment. Because of potentially significant liability issues with Norms if not properly managed, the development of quantitative relationships between TENORMs field measurement techniques and laboratory analysis present a practical approach in facilitating the interim safe decision process since laboratory results can take days. The primary objective of this study was to evaluate the relationships between direct measurements of field radioactivity and various laboratory batch techniques using data collection technologies for NORM and actual laboratory radioactivity concentrations. The significance of selected soil characteristics that may improve or confound these relationships in the formulation of empirical models was also achieved as an objective. The soil samples used in this study were collected from 4 different locations in western Canada and represented a wide range in terms of their selected chemical and physical properties. Multiple regression analyses for both field and batch data showed a high level of correlation between radionuclides Ra-226 and Ra-228 as a function of data collection technologies and relevant soil parameters. All R2 values for the empirical models were greater than 0.80 and significant at P<0.05. The creation of these empirical models could be valuable in improving predictability of radium contamination in soils and therefore, reduce analytical costs as well as environmental liabilities. PMID- 17849308 TI - Optimization of nitrogen removal in a sequencing batch reactor system by variation of the time distribution. AB - In this study, we investigated the variations of the nitrogen removal and mass balance of a sequencing batch reactor (SBR) system with the duration of the second anoxic period (the anoxic (II) period); durations of 0, 70, 100, and 130 minutes were tested in one cycle of SBR operation to determine the optimum conditions for the operation of the SBR and increase its nitrogen removal efficiency. The SBR system was operated under the conditions as follows: a sludge retention time (SRT) of 17.5 days, an operation time of 6 hours per cycle, a hydraulic retention time (HRT) of 12 hours, an influent COD loading of 0.4 kg/m3/day, and an influent nitrogen loading of 0.068 kgT-N/m3/day. For anoxic (II) phase duration times of 0, 70, 100, and 130 minutes, the amounts of nitrogen removed in the clarified water effluent for the synthetic wastewater were 73.1, 64.9, 59.0, and 49.3 mg/cycle, with nitrogen removal percentages of 59.7, 65.4, 68.8, and 73.8%, respectively. The amounts of nitrogen removed during the sludge waste process were 21.8, 22.0, 22.4, and 22.3 mg/cycle, respectively, indicating that the amount of nitrogen removed during the sludge waste process is not affected by changes in the time allotted to the anoxic (II) period. The amounts of nitrogen removed by denitrification were 76.5, 83.0, 90.5, and 96.5 mg/cycle, respectively indicating that increasing the duration of the anoxic (II) period increases the efficiency of nitrogen removal. The nitrogen mass balances were calculated as the percentages of nitrogen removed in the clarified water effluent or by denitrification and sludge waste processing in each cycle of SBR operation and were found to be excellent: 96.8%, 96.3%, 96.8%, and 95.2% for anoxic (II) phase durations of 0, 70, 100, and 130 minutes, respectively. PMID- 17849309 TI - Determination of chemical oxygen demand (COD) using ultrasound digestion and oxidation-reduction potential-based titration. AB - A new method for determining wastewater chemical oxygen demand (COD) using ultrasonic digestion and titration based on oxidation reduction potential (ORP) was developed. COD values of potassium hydrogen phthalate solution obtained by ultrasonic digestion were well matched with those obtained using Standard Methods. When applied to determine COD of real wastewater collected from a local treatment plant, results from the new method were within 80% to 90% of those obtained using Standard Methods. Nonetheless, the proposed strategy has the potential to be implemented into an online COD analyzing system. PMID- 17849310 TI - Biological treatment of sewage treatment plant sludge by pure bacterial culture with optimum process conditions in a stirred tank bioreactor. AB - Biological treatment of sewage treatment plant (STP) sludge by potential pure bacterial culture (Bacillus sp.) with optimum process conditions for effective biodegradation and bioseparation was carried out in the laboratory. The effective and efficient bioconversion was evaluated with the treatment of pure bacterial culture and existing microbes (uninnoculated) in sludge. The optimum process conditions i.e., temperature, 40 degrees C; pH, 6; inoculum, 5% (v/v); aeration, 1 vvm; agitation speed, 50 rpm obtained from the previous studies with chemical oxygen demand COD at 30 mgL(-1) were applied for the biological treatment of sludge. The results indicated that pure bacterial culture (Bacillus sp.) showed higher degradation and separation of treated sludge compared to treatment with the existing mixed microbes in a stirred tank bioreactor. The treated STP sludge by potential pure bacterial culture and existing microbes gave 30% and 11%; 91.2% and 59.1; 88.5% and 52.3%; 98.4% and 51.3%; 96.1% and 75.2%; 99.4% and 72.8% reduction of total suspended solids (TSS, biosolids), COD, soluble protein, turbidity, total dissolved solids (TDS) and specific resistance to filtration (SRF), respectively within 7 days of treatment. The pH was observed at 6.5 and 4 during the treatment of sludge by pure culture and existing microbes, respectively. PMID- 17849311 TI - Dissolved phosphorus levels in fresh municipal wastewater. AB - The influence of wastewater lag-time to the concentrations of dissolved phosphorus was investigated. The dissolved phosphorus levels of fresh municipal wastewater and the rate at which phosphorus dissolves in untreated municipal water was studied. Dissolved phosphorus initially accounted for 34% of total phosphorus in the used water. The level of dissolved phosphorus in wastewater doubled during half a year of storage. The dissolving of phosphorus was most rapid in the first 10 days when dissolved phosphorus levels increased by approximately 1% per day. PMID- 17849312 TI - Phosphorus treatment of secondary municipal effluent using oven-dried alum residual. AB - This study aims to investigate the effectiveness of alum residuals generated during drinking water treatment for adsorption of phosphorus from secondary municipal effluent. Bench-scale experiments (batch and fixed bed column tests) were conducted using oven-dried alum residuals. Experimental results observed maximum phosphorus removal of 91%-98% using alum residual concentrations of 4 g/L to 16 g/L. Oven-dried alum residual was a more effective adsorbent for orthophosphate phosphorus than total phosphorus. Effluent pH levels were suitable for surface water disposal with little or no lime addition. Aluminum leaching from oven-dried alum residual was not high enough to cause toxicity for aquatic species in surface water. Oven-dried alum residuals were also able to adsorb organic matter. The results indicated that oven-dried alum residuals have potential to provide a low cost technological solution for small- and medium sized municipalities. PMID- 17849314 TI - Herpes simplex virus type 1 ICP4 deletion mutant virus d120 infection failed to induce apoptosis in nerve growth factor-differentiated PC12 cells. AB - It has been suggested that terminally differentiated neuronal cells and mitotic cells respond differently in many aspects to herpes simplex virus type 1 (HSV-1) infection. The ICP4-deleted, Us3-defective, HSV-1 mutant strain d120 induces classical apoptosis in a variety of mitotic cell lines. Its behavior in postmitotic cells is not known. Here the authors report that mutant d120 virus failed to induce apoptosis in neuronal-like, nerve growth factor (NGF) differentiated PC12 cells. More strikingly, rather than inducing apoptosis, d120 infection prolonged the life of nondividing NGF-differentiated PC12 cells in the culture flask. The virus genome had a half-life of 30 days. Unlike in other cells, such as Vero, neither wild-type nor d120 infection of NGF-differentiated PC12 cells induced the nuclear factor (NF)-kappa B p65 pathway, which has been associated with virus-induced apoptosis. Thus, the authors demonstrate, for the first time, that a potent apoptosis inducer mutant d120 failed to induce apoptosis in neuronal-like NGF-differentiated PC12 cells, unlike a number of other cell lines studied. The possible mechanisms involved in the failure of d120 to induce apoptosis in neuronal-like NGF-differentiated PC12 cells are discussed. PMID- 17849313 TI - Impact of human immunodeficiency virus (HIV) subtypes on HIV-associated neurological disease. AB - Among the many variables affecting transmission and pathogenesis of the human immunodeficiency virus type 1(HIV-1), the effects of HIV subtypes, or clades, on disease progression remain unclear. Although debated, some studies have found that the variable env and pol sequences of different subtypes of HIV-1 may endow some subtypes with greater degrees of cell tropism, virulence, and drug resistance, which may lead to differences in overall disease progression. HIV associated dementia (HAD) appears to be associated with viral diversity and markers of immune activation. Africa has the highest prevalence of HIV, largest viral diversity, and is where clade recombination occurs most frequently. All of these factors would suggest that HAD would pose the largest threat in this region of the world. Although investigations into the effects of different subtypes on overall disease progression are well documented, few have looked into the effects of subtypes on neurological disease progression. This review highlights the need for more international research involving the neurological effects and especially the clinical presentation of dementia for the entire range of the group M HIV-1 subtypes. PMID- 17849315 TI - Characterization of peripheral blood human immunodeficiency virus isolates from Hispanic women with cognitive impairment. AB - Human immunodeficiency virus type 1 (HIV-1) tropism plays an important role in HIV-associated dementia. In this study, aimed at determining if the tropism and coreceptor usage of circulating viruses correlates with cognitive function, the authors isolated and characterized HIV from the peripheral blood of 21 Hispanic women using antiretroviral therapy. Macrophage tropism was determined by inoculation of HIV isolates onto monocyte-derived macrophages and lymphocyte cultures. To define coreceptor usage, the HIV isolates were inoculated onto the U87.CD4 glioma cell lines with specific CCR5 and CXCR4 coreceptors. HIV isolates from cognitively impaired patients showed higher levels of replication in mitogen stimulated peripheral blood mononuclear cells than did isolates from patients with normal cognition (P < .05). The viral growth of HIV primary isolates in macrophages and lymphocytes did not differ between patients with and those without cognitive impairment. However, isolates from the cognitively impaired women preferentially used the X4 coreceptor (P < .05). These phenotypic studies suggest that cognitively impaired HIV-infected women receiving treatment may have a more highly replicating and more pathogenic X4 virus in the circulation that could contribute to their neuropathogenesis. PMID- 17849316 TI - The tyrosine kinase inhibitor imatinib mesylate delays prion neuroinvasion by inhibiting prion propagation in the periphery. AB - Prion diseases are fatal neurodegenerative disorders with no effective therapy. A hallmark of prion disease is the conversion of the normal cellular form of prion protein PrP(C) into a disease-associated isoform PrP(Sc). The authors recently have shown that a tyrosine kinase inhibitor, imatinib mesylate, induces clearance of PrP(Sc) via specific inhibition of c-Abl in prion-infected cell culture models. In this study, the authors assessed the in vivo effects of imatinib mesylate on prion disease using a scrapie-infected mouse model and further investigated prion infectivity of the drug-treated scrapie-infected neuroblastoma (ScN2a) cells. The authors found that imatinib mesylate abolished prion infectivity to almost undetectable level in ScN2a cells and the level of PrP(Sc) was significantly decreased by the drug in scrapie-infected mouse spleens as well as in ScN2a cells. Moreover, the drug treatment at an early phase of peripheral scrapie infection delayed the appearance of PrP(Sc) in the central nervous system (CNS) and onset of clinical disease in mice. However, neither intraperitoneal nor intracerebroventricular delivery of the drug exerted any PrP(Sc) clearance effect in the CNS. PMID- 17849318 TI - Evidence for human herpesvirus 6 variant A antibodies in multiple sclerosis: diagnostic and therapeutic implications. AB - Human herpesvirus 6 (HHV-6) has been linked to the pathogenesis of multiple sclerosis (MS). HHV-6 antibodies in serum and cerebrospinal fluid (CSF) of 27 patients with clinically definite MS (CDMS) were compared with age- and sex matched controls, including various other neurological diseases and symptoms (OND). In addition, we studied a series of 19 patients with clinically or laboratory supported possible MS (CPMS). Seroprevalence to HHV-6A was 100% in patients with MS, both in CDMS and CPMS, compared to 69.2% in patients with OND (P = .001 and .007). The mean immunoglobulin G (IgG) titers were significantly higher in patients with CDMS and CPMS than in controls (P = .005 and .00002). The proportion of acute primary infections without CSF involvement was similar in all groups; however, primary infections with intrathecal HHV-6 antibody production were more frequent in MS. In CSF, HHV-6A-specific antibodies were present in three (11.5%) and four (21.1%) patients with CDMS and CPMS, compared to none with OND (P = .06 and .01, respectively). Serological suggestions to HHV-6A infection occurred more often in both CDMS and CPMS than in OND (14.8% versus 21.1% versus 3.8%). We conclude that a subpopulation of MS patients, and even a greater proportion of possible MS subjects, has serological evidence of HHV-6A infection, which might provide new markers for diagnosis and therapy. PMID- 17849317 TI - Characterization of JC virus in cerebrospinal fluid from HIV-1 infected patients with progressive multifocal leukoencephalopathy: insights into viral pathogenesis and disease prognosis. AB - OBJECTIVES: To analyze virological and immunological features of AIDS-related progressive multifocal leukoencepalophathy (PML) and their association to disease prognosis. METHODS: In HIV-infected patients with virologically confirmed PML, JC virus (JCV) DNA load and levels of Macrophage Chemoattractant Protein (MCP)-1 were determined in cerebrospinal fluid. JCV genotypes, rearrangements and JCV DNA binding sites for cellular transcription factors were analyzed by sequencing the viral VP1 region and regulatory region (RR). RESULTS: 45 patients were analyzed: 60% were exposed to highly active antiretroviral therapy (HAART) after PML and 24% before the disease onset. JCV DNA load in cerebrospinal fluid was a strong predictor of patients survival. Lower levels of JCV DNA in cerebrospinal fluid were associated with the following virologic factors: viral genotype 4 (p = 0.043), more rearrangements in the RR (p = 0.046), duplication of RR block B (p = 0.028), and duplication of binding sites for cellular transcription factor NF-1 (p = 0.060). In patients with prior antiretroviral exposure there was a trend towards a higher number of binding sites for cellular transcription factors (p = 0.068). Lower JCV load was also predicted by exposure to HAART (p = 0.010), higher baseline CD4 counts (p = 0.009) and higher cerebrospinal fluid MCP-1 levels (p = 0.036). In a multiple regression model, MCP-1 levels were independently associated with JCV load. CONCLUSION: HAART leads to a partial immune-mediated control of JCV replication; the virus may tend to escape through the selection of rearrangements in the RR, some associated with enhanced viral replication efficiency, other resulting in multiplication of binding sites for cellular transcription factors. PMID- 17849319 TI - Semliki Forest virus vectors with mutations in the nonstructural protein 2 gene permit extended superinfection of neuronal and non-neuronal cells. AB - Semliki Forest virus (SFV) vectors are widely used in neurobiological studies because they efficiently infect neurons. As with any viral vector, they possess a limited cloning capacity, so infection with different SFV vectors may be required to introduce multiple transgenes into individual cells. However, this approach is limited by superinfection exclusion. The authors examined marker expression in baby hamster kidney cells, mouse cortical neurons, and rat hippocampal neurons using different fluorophore-encoding vectors that are based on the wild-type SFV4 strain and on the less cytopathic SFV4(PD) mutant, which carries two point mutations in nonstructural protein 2. For every fluorophore tested, SFV4(PD) gave higher (up to 22-fold) expression compared to SFV4. In infections using two and three different vectors, SFV4 caused relatively few multifluorescent baby hamster kidney cells when applied at 0-s, 15-min, or 2-h intervals. In contrast, SFV4(PD) permitted significantly enhanced marker coexpression, resulting in 46% doubly and 21% triply fluorescent baby hamster kidney cells, and 67% to 8% doubly fluorescent cortical and hippocampal neurons. At 15-min or 2-h addition intervals, SFV4(PD) still permitted 23% to 36% doubly fluorescent baby hamster kidney cells. The increased efficiency of SFV4(PD) in coexpressing separate markers from different viral particles suggests that mutations in nonstructural protein 2 affect alphaviral superinfection exclusion. The results demonstrate that SFV4(PD) is well-suited to coexpress multiple proteins in neuronal and non neuronal cells. This capability is particularly valuable to express the various components of heteromeric protein complexes, especially when the individual cDNAs cannot be combined into single SFV particles. PMID- 17849320 TI - Safety and efficacy of interferon-alpha in 167 patients with human T-cell lymphotropic virus type 1-associated myelopathy. AB - A postmarketing surveillance study was undertaken to investigate the safety and efficacy of interferon-alpha for human T-cell lymphotropic virus type 1 (HTLV-1) associated myelopathy (HAM) under routine treatment conditions. A total of 273 cases from 91 medical institutions were registered into the survey. So far, 167 cases had been evaluated for safety and 152 for efficacy. The efficacy evaluation was rated based on clinical symptoms of HAM. Efficacy ratio (rate of patients assessed as "modest to markedly improved" and "mildly improved") at 4 weeks was 66.2%. Factors that significantly affected efficacy ratio at 4 weeks was initial Osame's motor disability score (OMDS) before interferon-alpha therapy and duration and stage of illness. Sustained improvement of OMDS for at least 5 months after stopping interferon-alpha was observed in 11 of 30 patients (36.7%). A total of 536 adverse drug reactions (ADRs) occurred in 146 patients, 46 of which were serious. Because some of these ADRs occurred late, it is necessary to watch out for them during long-term treatment. PMID- 17849322 TI - Envelope protein Us9 is required for the anterograde transport of bovine herpesvirus type 1 from trigeminal ganglia to nose and eye upon reactivation. AB - In this study, the authors examined the role of bovine herpesvirus type 1 (BHV-1) Us9 in the anterograde transport of the virus from trigeminal ganglia (TG) to nose and eye upon reactivation from latency. During primary infection, both BHV-1 Us9-deleted and BHV-1 Us9-rescued viruses replicated efficiently in the nasal and ocular epithelium. However, upon reactivation from latency, only the BHV-1 Us9 rescued virus could be isolated in the nasal and ocular shedding. By real-time polymerase chain reaction, comparable DNA copy numbers were detected in the TGs during latency and reactivation for both the viruses. Therefore, Us9 is essential for reactivation of the virus in the TG and anterograde axonal transport from TG to nose and eye. PMID- 17849321 TI - JAK-STAT signaling pathways are activated in the brain following reovirus infection. AB - Reovirus infection provides a classic experimental model system for studying the pathogenesis of viral infections of the central nervous system (CNS), with apoptosis acting as the major mechanism of cell death. The authors have examined the role of signal transducer and activator of transcription (STAT)1, a component of Janus-activated kinase (JAK)-STAT signaling, a pathway implicated in antiviral responses and pathways regulating apoptosis, following reovirus infection. Infection of primary cortical neuron cultures with reovirus serotype 3 strain Abney (T3A) resulted in phosphorylation of STAT1 at sites critical for transcriptional activity. Activated STAT1 was also detected in the brain of neonatal mice following T3A infection, with a nuclear pattern of expression in areas of virus-induced injury. Activation of STAT proteins is typically mediated by JAKs. The authors observed JAK2 phosphorylation (Tyr 1007/1008) in brain lysates from T3A-infected mice. Inhibition of JAK activity with the inhibitor AG 490 blocked reovirus-induced STAT1 activation in neuronal cultures, indicating reovirus-induced STAT activation is JAK dependent. Pretreatment of neuronal cultures with antibody raised against interferon (IFN)-alpha/betaR2 inhibited T3A induced STAT1 phosphorylation, whereas neither IFN-gamma or IFN-gammaR2 antibody pretreatment had any effect on T3A-induced STAT1 phosphorylation. Mice lacking the STAT1 gene demonstrated increased susceptibility to reovirus infection, with increased mortality and higher viral titers in the brain compared to wild-type animals. The results demonstrate activation of a type I IFN-mediated, JAK dependent STAT signaling pathway following reovirus infection and suggest that STAT1 is a key component of host defense mechanisms against reovirus infection in the brain. PMID- 17849325 TI - Estimating a binary character's effect on speciation and extinction. AB - Determining whether speciation and extinction rates depend on the state of a particular character has been of long-standing interest to evolutionary biologists. To assess the effect of a character on diversification rates using likelihood methods requires that we be able to calculate the probability that a group of extant species would have evolved as observed, given a particular model of the character's effect. Here we describe how to calculate this probability for a phylogenetic tree and a two-state (binary) character under a simple model of evolution (the "BiSSE" model, binary-state speciation and extinction). The model involves six parameters, specifying two speciation rates (rate when the lineage is in state 0; rate when in state 1), two extinction rates (when in state 0; when in state 1), and two rates of character state change (from 0 to 1, and from 1 to 0). Using these probability calculations, we can do maximum likelihood inference to estimate the model's parameters and perform hypothesis tests (e.g., is the rate of speciation elevated for one character state over the other?). We demonstrate the application of the method using simulated data with known parameter values. PMID- 17849323 TI - Virological and immunological characteristics of fatal Epstein-Barr virus mononucleosis in a 17-year-old Caucasian male presenting with meningoencephalitis and hemophagocytic syndrome. AB - In this report, the authors present a detailed immunological and virological assessment of an immunocompetent 17-year-old Caucasian male with a fatal Epstein Barr virus (EBV) infectious mononucleosis presenting with meningoencephalitis and hemophagocytic syndrome. The patient with serologically confirmed EBV infectious mononucleosis was admitted to the hospital because of 3 weeks' fever. Fine-needle aspiration of lymph nodes showed reactive hyperplasia with prominent hemophagocytosis. Percentages of intracellular interferon-gamma (IFN-gamma) in CD4(+) and CD8(+) T cells in the peripheral blood progressively increased during the course of disease (10.2% and 8.5% on day 35; 30.1% and 53.2% on day 44; 42.2% and 75.2% on day 50; 36.1% and 50.6% on day 59, respectively). On day 50, the patient developed meningoencephalitis. Brain computed tomography (CT) was normal. Brain magnetic resonance imaging (MRI) showed multifocal inflammatory lesions in frontal and temporal cortex of the right hemisphere as well as severe perivascular inflammatory reaction. The patient was treated with steroids, cyclosporin A, and methotrexate intratecally. Following treatment, EBV viremia in the blood and cerebrospinal fluid (CSF) decreased from pretreatment values (54,490 copies of EBV DNA/ml and 39,500 copies/ml, respectively) to 8715 copies/ml in the blood and 14,690 in the CSF. Despite treatment, the patient remained unconscious and died of sepsis and pneumonia 3 months after initial symptoms. Immunohistochemical staining showed the presence of EBV in both perivascular infiltrates and grey matter. Enhanced Th1 response as shown by high levels of IFN-gamma in peripheral blood lymphocytes may be a predictor of severe complications during acute EBV infection. Early implementation of immunosuppressive therapy in these patients should be considered. PMID- 17849326 TI - Exploring fast computational strategies for probabilistic phylogenetic analysis. AB - In recent years, the advent of Markov chain Monte Carlo (MCMC) techniques, coupled with modern computational capabilities, has enabled the study of evolutionary models without a closed form solution of the likelihood function. However, current Bayesian MCMC applications can incur significant computational costs, as they are based on a full sampling from the posterior probability distribution of the parameters of interest. Here, we draw attention as to how MCMC techniques can be embedded within normal approximation strategies for more economical statistical computation. The overall procedure is based on an estimate of the first and second moments of the likelihood function, as well as a maximum likelihood estimate. Through examples, we review several MCMC-based methods used in the statistical literature for such estimation, applying the approaches to constructing posterior distributions under non-analytical evolutionary models relaxing the assumptions of rate homogeneity, and of independence between sites. Finally, we use the procedures for conducting Bayesian model selection, based on Laplace approximations of Bayes factors, which we find to be accurate and computationally advantageous. Altogether, the methods we expound here, as well as other related approaches from the statistical literature, should prove useful when investigating increasingly complex descriptions of molecular evolution, alleviating some of the difficulties associated with nonanalytical models. PMID- 17849327 TI - New approaches to phylogenetic tree search and their application to large numbers of protein alignments. AB - Phylogenetic tree estimation plays a critical role in a wide variety of molecular studies, including molecular systematics, phylogenetics, and comparative genomics. Finding the optimal tree relating a set of sequences using score-based (optimality criterion) methods, such as maximum likelihood and maximum parsimony, may require all possible trees to be considered, which is not feasible even for modest numbers of sequences. In practice, trees are estimated using heuristics that represent a trade-off between topological accuracy and speed. I present a series of novel algorithms suitable for score-based phylogenetic tree reconstruction that demonstrably improve the accuracy of tree estimates while maintaining high computational speeds. The heuristics function by allowing the efficient exploration of large numbers of trees through novel hill-climbing and resampling strategies. These heuristics, and other computational approximations, are implemented for maximum likelihood estimation of trees in the program Leaphy, and its performance is compared to other popular phylogenetic programs. Trees are estimated from 4059 different protein alignments using a selection of phylogenetic programs and the likelihoods of the tree estimates are compared. Trees estimated using Leaphy are found to have equal to or better likelihoods than trees estimated using other phylogenetic programs in 4004 (98.6%) families and provide a unique best tree that no other program found in 1102 (27.1%) families. The improvement is particularly marked for larger families (80 to 100 sequences), where Leaphy finds a unique best tree in 81.7% of families. PMID- 17849328 TI - Not forgetting forgetting. PMID- 17849329 TI - Response to open commentaries for "Propranolol and the prevention of post traumatic stress disorder: is it wrong to erase the 'sting' of bad memories?". PMID- 17849330 TI - Rethinking neuroethics in the light of the extended mind thesis. AB - The extended mind thesis is the claim that mental states extend beyond the skulls of the agents whose states they are. This seemingly obscure and bizarre claim has far-reaching implications for neuroethics, I argue. In the first half of this article, I sketch the extended mind thesis and defend it against criticisms. In the second half, I turn to its neuroethical implications. I argue that the extended mind thesis entails the falsity of the claim that interventions into the brain are especially problematic just because they are internal interventions, but that many objections to such interventions rely, at least in part, on this claim. Further, I argue that the thesis alters the focus of neuroethics, away from the question of whether we ought to allow interventions into the mind, and toward the question of which interventions we ought to allow and under what conditions. The extended mind thesis dramatically expands the scope of neuroethics: because interventions into the environment of agents can count as interventions into their minds, decisions concerning such interventions become questions for neuroethics. PMID- 17849331 TI - Propranolol and the prevention of post-traumatic stress disorder: is it wrong to erase the "sting" of bad memories? AB - The National Institute of Mental Health (Bethesda, MD) reports that approximately 5.2 million Americans experience post-traumatic stress disorder (PTSD) each year. PTSD can be severely debilitating and diminish quality of life for patients and those who care for them. Studies have indicated that propranolol, a beta-blocker, reduces consolidation of emotional memory. When administered immediately after a psychic trauma, it is efficacious as a prophylactic for PTSD. Use of such memory altering drugs raises important ethical concerns, including some futuristic dystopias put forth by the President's Council on Bioethics. We think that adequate informed consent should facilitate ethical research using propranolol and, if it proves efficacious, routine treatment. Clinical evidence from studies should certainly continue to evaluate realistic concerns about possible ill effects of diminishing memory. If memory-attenuating drugs prove effective, we believe that the most immediate social concern is the over-medicalization of bad memories, and its subsequent exploitation by the pharmaceutical industry. PMID- 17849332 TI - Spinoza's Passions. PMID- 17849333 TI - Debunking alarmist objections to the pharmacological prevention of PTSD. PMID- 17849334 TI - Clarifying the debate over therapeutic forgetting. PMID- 17849335 TI - Necessary forgetting: on the use of propranolol in post-traumatic stress disorder management. PMID- 17849336 TI - Preventing post-traumatic stress disorder or pathologizing bad memories? PMID- 17849337 TI - Propranolol, cognitive biases, and practical decision-making. PMID- 17849338 TI - Emotions, memory suppression, and identity. PMID- 17849339 TI - The moral costs of prophylactic propranolol. PMID- 17849340 TI - Propranolol and its potential inhibition of positive post-traumatic growth. PMID- 17849341 TI - Neuroethical concerns about moderating traumatic memories. PMID- 17849342 TI - Memory-altering drugs: shifting the paradigm of informed consent. PMID- 17849343 TI - On moralizing and hidden agendas: the pot and the kettle in political bioethics. PMID- 17849344 TI - Functional neuroimaging and the law: trends and directions for future scholarship. AB - Under the umbrella of the burgeoning neurotransdisciplines, scholars are using the principles and research methodologies of their primary and secondary fields to examine developments in neuroimaging, neuromodulation and psychopharmacology. The path for advanced scholarship at the intersection of law and neuroscience may clear if work across the disciplines is collected and reviewed and outstanding and debated issues are identified and clarified. In this article, I organize, examine and refine a narrow class of the burgeoning neurotransdiscipline scholarship; that is, scholarship at the interface of law and functional magnetic resonance imaging (fMRI). PMID- 17849345 TI - Some thoughts about the evaluation of non-clinical functional magnetic resonance imaging. PMID- 17849346 TI - The neuroscience of functional magnetic resonance imaging fMRI for deception detection. PMID- 17849347 TI - Neuroimaging, entrapment, and the predisposition to crime. PMID- 17849348 TI - Neuroimaging as evidence. PMID- 17849349 TI - The use of functional neuroimaging technology in the assessment of loss and damages in tort law. PMID- 17849350 TI - Neuroscience, emotional harm, and emotional distress tort claims. PMID- 17849351 TI - Inadmissible, eh? PMID- 17849352 TI - Functional neuroimaging and the law: a canadian perspective. PMID- 17849353 TI - Brain privacy: how can we protect it? PMID- 17849354 TI - Learning from law's past: a call for caution in incorporating new innovations in neuroscience. PMID- 17849355 TI - Pulmonary neuroendocrine cell hyperplasia: identification, diagnostic criteria and incidence in untreated ageing rats of different strains. AB - Pulmonary Neuroendocrine Cells (PNEC) are found as clusters called neuroepithelial bodies (NEB) or as single cells scattered in the respiratory epithelium. Pulmonary neuroendocrine cell hyperplasia is recorded in humans and experimentally manipulated rodents. The objectives of this work were to identify the optimal immunohistochemical markers for PNEC in the rat for use on paraffin embedded, formalin-fixed material and to provide the first comparative incidence of PNEC hyperplasia in untreated 2-year-old rats of different strains. Calcitonin gene related peptide (CGRP) and protein G product 9.5 (PGP9.5) antibodies identified PNEC consistently and selectively. In contrast, PNEC did not express chromogranin-A or S-100. PNEC hyperplasia was defined as foci of PNEC with greater than 40 nuclei, excluding overlying respiratory epithelium and submucosal PNEC. PNEC hyperplasia was observed at low incidence (0-7%) in untreated 2-year old Sprague-Dawley, Han Wistar and Wistar rats but not Fischer 344 rats. This is the first report of spontaneous PNEC hyperplasia in rats. The cause of this hyperplasia is unknown, but experimental models that induce PNEC hyperplasia by causing bronchiolar cell injury are discussed. PNEC neoplasia in the rat is unreported in the literature and was not observed in animals examined in this study. PMID- 17849357 TI - Evaluation of organ weights for rodent and non-rodent toxicity studies: a review of regulatory guidelines and a survey of current practices. AB - The Society of Toxicologic Pathology convened a working group to evaluate current practices regarding organ weights in toxicology studies. A survey was distributed to pharmaceutical, veterinary, chemical, food/nutritional and consumer product companies in Europe, North America, and Japan. Responses were compiled to identify organs routinely weighed for various study types in rodent and non rodent species, compare methods of organ weighing, provide perspectives on the value of organ weights and identify the scientist(s) responsible for organ weight data interpretation. Data were evaluated as a whole as well as by industry type and geographic location. Regulatory guidance documents describing organ weighing practices are generally available, however, they differ somewhat dependent on industry type and regulatory agency. While questionnaire respondents unanimously stated that organ weights were a good screening tool to identify treatment related effects, opinions varied as to which organ weights are most valuable. The liver, kidneys, and testes were commonly weighed and most often considered useful by most respondents. Other organs that break were commonly weighed included brain, adrenal glands, ovaries, thyroid glands, uterus, heart, and spleen. Lungs, lymph nodes, and other sex organs were weighed infrequently in routine studies, but were often weighed in specialized studies such as inhalation, immunotoxicity, and reproduction studies. Organ-to-body weight ratios were commonly calculated and were considered more useful when body weights were affected. Organ to brain weight ratios were calculated by most North American companies, but rarely according to respondents representing veterinary product or European companies. Statistical analyses were generally performed by most respondents. Pathologists performed interpretation of organ weight data for the majority of the industries. PMID- 17849358 TI - Society of Toxicologic Pathology position paper: organ weight recommendations for toxicology studies. AB - The evaluation of organ weights in toxicology studies is an integral component in the assessment of pharmaceuticals, chemicals, and medical devices. The Society of Toxicologic Pathology (STP) has created recommendations for weighing organs in GLP general toxicology studies lasting from 7 days to 1 year. The STP recommends that liver, heart, kidneys, brain, testes, and adrenal glands be weighed in all multidose general toxicology studies. Thyroid gland and pituitary gland weights are recommended for all species except mice. Spleen and thymus should be weighed in rodent studies and may be weighed in non-rodent studies. Weighing of reproductive organs is most valuable in sexually mature animals. Variability in age, sexual maturity, and stage of cycle in non-rodents and reproductive senescence in female rodents may complicate or limit interpretation of reproductive organ weights. The STP recommends that testes of all species be weighed in multidose general toxicology studies. Epididymides and prostate should be weighed in rat studies and may be weighed on a case-by-case basis in non rodent and mouse studies. Weighing of other organs including female reproductive organs should be considered on a case-by-case basis. Organ weights are not recommended for any carcinogenicity studies including the alternative mouse bioassays. Regardless of the study type or organs evaluated, organ weight changes must be evaluated within the context of the compound class, mechanism of action, and the entire data set for that study. PMID- 17849359 TI - Substance P and its receptors -- a potential target for novel medicines in malignant brain tumour therapies (mini-review). AB - Tachykinins are excitatory neuropeptides synthesised in neuronal and glial cells of the human central and peripheral nervous system. They participate in both physiological and certain pathological conditions, i.e. synaptic transmission, nociception and neuroimmunomodulation. Tachykinins act as excitatory neurotransmitters and/or neuromodulators and induce DNA synthesis leading to stimulation of cell division and proliferation. Their biological responses are triggered via the well-established tachykinin receptors NK1, NK2 and NK3 that belong to the G protein-coupled receptor family (GPCRs). Substance P is the most important member of the tachykinin family that constitutes the major endogenous ligand for the NK1 receptor type. The presence of functional NK1 receptors has been documented in malignant brain tumours of glial origin. It has been evidenced that SP-NK1 receptor communication is involved in glioma development and progression. It is possible because the tumour cells display SP-mediated autocrine activity, the ability of cytokines stimulation and MAP kinases activation. It has been suggested that SP receptor antagonists application might be useful in attempts directed at anti-cancer therapy. PMID- 17849360 TI - Size frequency distributions of abnormal protein deposits in Alzheimer's disease and variant Creutzfeldt-Jakob disease. AB - The size frequency distributions of beta-amyloid (A beta) and prion protein (PrPsc) deposits were studied in Alzheimer's disease (AD) and the variant form of Creutzfeldt-Jakob disease (vCJD) respectively. All size distributions were unimodal and positively skewed. A beta deposits reached a greater maximum size and their distributions were significantly less skewed than the PrPsc deposits. All distributions were approximately log-normal in shape but only the diffuse PrPsc deposits did not deviate significantly from a log-normal model. There were fewer larger classic A beta deposits than predicted and the florid PrPsc deposits occupied a more restricted size range than predicted by a log-normal model. Hence, A beta deposits exhibit greater growth than the corresponding PrPsc deposits. Surface diffusion may be particularly important in determining the growth of the diffuse PrPsc deposits. In addition, there are factors limiting the maximum size of the A beta and florid PrPsc deposits. PMID- 17849361 TI - Morphological analysis of vascular density in ependymomas. AB - Ependymomas generally show slow growth rate and are associated with a long clinical history. In some cases however the biology of these tumours is considered to be unpredictable on the basis of histologic criteria. Density of microvessels was shown to serve in various malignant neoplasms as a prognostic factor that correlates with increased risk of metastasis and overall free survival. Some data suggest that density of blood vessels may be of prognostic value also in patients with neuroepithelial tumours. The aim of this study was to determinate whether that observation can be applied to ependymomas. The materials included 51 ependymomas G2 and G3 according to the WHO classification. Vasculature was visualized immunohistochemically in paraffin-embedded sections of tumour samples with CD31 and FVIII antibody. Density of blood vessels was calculated using a computed image analyzing system. The data were statistically evaluated. The density of blood vessels in anaplastic (WHO G3) ependymomas was shown to be significantly higher than that in WHO G2 type of the tumour, while there was no statistical difference between subtypes of WHO G2 ependymomas. The results suggest a connection between density of vasculature and the degree of histological malignancy in gliomas of ependymal derivation. PMID- 17849362 TI - Advanced reactive astrogliosis associated with hemangioblastoma versus astroglial vascular neoplasm ("angioglioma"). AB - Hemangioblastomas of the central nervous system are often accompanied by a cyst exhibiting an extensive astroglial reaction. The cyst's wall might be composed of various astroglial elements including reactive pilocytic or gemistocytic and hypertrophic astrocytes. The small tissue samples composed of compact gliotic tissue are sometimes nonrepresentative for primary hemangioblastoma tumour and might be confused with both pilocytic and diffuse infiltrative astrocytoma. Moreover, vascular anomalies of hemangioblastoma-like pattern could be combined with true neoplastic glial proliferation. Such association of glioma with certain types of vascular anomalies has been designated as angioglioma. In the current study we evaluated a series of hemangioblastomas accompanied by advanced astrogliosis of adjacent brain tissue. In some cases the histopathological features of pilocytic gliosis with numerous Rosenthal fibres and eosinophilic granular bodies strongly suggest the diagnosis of pilocytic astrocytoma. One tumour was identified as an angioglioma exhibiting a combination of hemangioblastoma-like tissue and pilocytic astrocytoma. The recognition of such an entity is important in differential tumour diagnosis and prognosis. PMID- 17849363 TI - Estimation of prognostic value of CD44 expression in neuroblastic tumours in children. AB - Adversities observed in treatment of children with neoplastic disease based on new diagnostic markers and new prognostic factors. Both of them allow prognosis to be established for a single patient. The aim of our study was to examine the expression of CD44 adhesion molecule in different histologic types in a neuroblastoma group of tumours (35 cases of neuroblastoma from current files and archives) and to estimate the possible prognostic value of CD44 expression by comparison with widely accepted prognostic markers and chosen histoclinical parameters (9 cases of neuroblastoma with follow-up data). We did not find a statistically significant correlation between CD44 expression and histologic type of the tumour. However, we found that all relapses appeared among patients with tumours with the strongest CD44 expression, and that in none of the investigated tumours without relapses was strong CD44 expression ever observed. We noticed CD44 expression in 88.88% of examined tissue samples which underwent statistical analysis and we found the strongest CD44 expression in tumours situated in the retroperitoneal space. Results of log-rank test and Kaplan-Meier estimation showed that a correlation between CD44 expression and survival time was close to a statistically significant value (p=0.065). We conclude that lack of a clear statistically significant correlation between CD44 expression and histoclinical parameters and currently known prognostic factors in our study is due to the presence of many CD44 isoforms, which cannot be distinguished with commercially used antibodies, but they may play a different role in pathogenesis and spread of neuroblastoma. PMID- 17849364 TI - Abnormal chaperone-mediated autophagy (CMA) in cardiomyocytes of a boy with Danon disease. AB - Ultrastructural analysis of the cardiomyocyte structure in Danon disease reveals dramatic accumulation of abnormal late autophagic vacuoles (AVd) suggestive of primary lysosomal defect. Moreover, the accumulation of AVd in cardiomyocytes is consistent with a decreased rate of autophagic to lysosomal trafficking. These results suggest that the loss of the LAMP-2 protein strongly inhibits uptake of proteins into lysosomes for degeneration. The significant reduction of chaperone mediated autophagy (CMA) activity in the affected cardiomyocytes induces a dramatic increase in the number and size of AVd and a severe reduction of myocardial contractility. PMID- 17849365 TI - Glioneuronal-mesenchymal tumour with malignant transformation. AB - We report a case of a 10-year-old girl with a tumour of the right temporoparietal region of the brain. The tumour consisted of three morphologically distinct portions: a well-differentiated one containing a mixture of a ganglioglioma with adipocytic-like cells and focal chondroid metaplasia, a separate island with neurocytic differentiation, and the malignant one, which exhibited an organoid pattern (trabecular and festooned) of primitive neuroectodemal tumour (PNET). We hypothesize that the latter component originated from the multicomponental glioneuronal tumour with mesenchymal differentiation and thus that lesion constituted an unusual example of malignant transformation of low-grade glioneuronal neoplasm. PMID- 17849366 TI - Primary pituitary lymphoma. AB - Primary CNS lymphoma (PCNSL) is now thought to constitute 3% of all intracranial neoplasms. PCNSL occurrence in the sella turcica region is an extremely rare finding. We present a 37-year-old male with primary pituitary lymphoma treated in our department. The patient, who had had no previous illnesses, was admitted to the hospital because of bilateral blurred vision. Findings on physical examination were normal except for temporal parts of field of vision deficit. No abnormalities were found in his bilateral ocular movement, facial sensory function or motor function. His blood count and biochemical profile were normal. Basic hormonal studies revealed no symptoms of panhypopituitarism. MRI demonstrated a large intrasellar mass with supra- and parasellar extension. MRS revealed decrease in NAA/tCr proportion and increase in Cho/NAA and Cho/tCr proportions. Endoscopic surgery was performed using the transsphenoidal approach. Histopathological examination demonstrated a large B-cell lymphoma. The patient received 6 cycles of CHOP chemotherapy. He was also irradiated with 6 MV photons to the whole brain to a total dose of 40 Gy and then there was a boost to the tumour to a total dose of 50 Gy. Next he was reoperated on with the fronto temporo-sphenoidal craniotomy approach and subtotal resection of the tumour was performed. After the treatment the visual disturbances significantly decreased. Control MRI revealed a stable remnant of the tumour. Nowadays the patient has 52 months' follow-up and he has only a stable, slight visual field deficit on the upper temporal side of the right eye. PMID- 17849368 TI - [New media in psychotherapy: virtual reality technologies]. PMID- 17849367 TI - Fatal stroke in a young cocaine drug addict: chemical hair analysis and cervical artery examination twenty months after death. AB - We present a case of a 26-year-old female who died of acute cerebral infarction after thrombosis of the left internal carotid artery, conceivably related to cocaine use. The forensic examination was performed only twenty months post mortem. Revaluation of clinical data was carried out after exhumation and forensic autopsy examination were done, including anatomic dissection of cervical vessels and histological and toxicological analyses. Interestingly, comparative histological examination of cervical arteries was more useful in determining the putative site of vascular damage than gross and histological examination of the brain itself, although the state of preservation of tissues was poor. In conclusion, when a vascular accident is suspected or has to be demonstrated, we suggest performing comparative histological examinations of selected artery samples, even several months after death. PMID- 17849369 TI - [Crash course "clinical research in psychosocial medicine": changes in research knowledge and subjective research competence]. AB - In the field of psychosocial medicine, there is a lack of structured training programs in clinical research methodology for young investigators. This study investigates changes in research knowledge and subjective research competence during a one-day crash course in clinical research. In addition, the participants evaluated the quality of the course. The crash course, held at the 2007 meeting of the German Council of Psychosomatic Medicine, consisted of 10 lessons regarding clinical study design, biostatistics, and publication of study results. Changes in research knowledge and subjective research competence were measured with multiple-choice and open-ended questions using a one-group pre-post-test design. All 11 participants (73 % male, mean age 37.0 +/- 9.5 years) completed the evaluations at the beginning and at the end of the course. The crash course was associated with a significant increase in research knowledge (effect size = 1.3; p < 0.001), but no significant change was found with respect to subjective research competence (effect size = 0.2; p = 0.52). Overall, the quality of the course was rated as excellent; 10 of the 11 participants (91 %) would participate again in a similar crash course. The substantial increase in research knowledge suggests that structured courses in clinical research methodology should regularly be offered to young investigators, e. g. within the scope of research meetings or other national structures. PMID- 17849370 TI - Effects of as-cast and wrought Cobalt-Chrome-Molybdenum and Titanium-Aluminium Vanadium alloys on cytokine gene expression and protein secretion in J774A.1 macrophages. AB - Insertion of metal implants is associated with a possible change in the delicate balance between pro- and anti-inflammatory proteins, probably leading to an unfavourable predominantly pro-inflammatory milieu. The most likely cause is an inappropriate activation of macrophages in close relation to the metal implant and wear-products. The aim of the present study was to compare surfaces of as cast and wrought Cobalt-Chrome-Molybdenum (CoCrMo) alloys and Titanium-Aluminium Vanadium (TiAlV) alloy when incubated with mouse macrophage J774A.1 cell cultures. Changes in pro- and anti-inflammatory cytokines (TNF-alpha, IL-6, IL alpha, IL-1beta, IL-10) and proteins known to induce proliferation (M-CSF), chemotaxis (MCP-1) and osteogenesis (TGF-beta, OPG) were determined by ELISA and Real Time reverse transcriptase - PCR (Real Time rt-PCR). Lactate dehydrogenase (LDH) was measured in the medium to asses the cell viability. Surface properties of the discs were characterised with a profilometer and with energy dispersive X ray spectroscopy. We here report, for the first time, that the prosthetic material surface (non-phagocytable) of as-cast high carbon CoCrMo reduces the pro inflammatory cytokine IL-6 transcription, the chemokine MCP-1 secretion, and M CSF secretion by 77%, 36%, and 62%, respectively. Furthermore, we found that reducing surface roughness did not affect this reduction. The results suggest that as-cast CoCrMo alloy is more inert than wrought CoCrMo and wrought TiAlV alloys and could prove to be a superior implant material generating less inflammation which might result in less osteolysis. PMID- 17849371 TI - C60 on gold: adsorption, motion, and viscosity. PMID- 17849373 TI - Health-related quality of life among patients with adenocarcinoma of the gastro oesophageal junction treated by gastrectomy or oesophagectomy. AB - BACKGROUND: Tumours of the gastro-oesophageal junction may be resected by total gastrectomy (TG) or transthoracic oesophagectomy (TTO). This study compared health-related quality of life (HRQL) following these procedures. METHODS: Prospective clinical and HRQL data (European Organization for Research and Treatment of Cancer QLQ-C30) were collected from 63 consecutive patients (20 TG and 43 TTO) before and 6 months after surgery for Siewert type I-III gastro oesophageal tumours. RESULTS: Questionnaire response rates exceeded 90 per cent. Patients were similar with respect to disease stage, treatment-related mortality and survival, but those selected for TTO were younger with less co-morbidity than those undergoing TG. These differences were reflected in baseline HRQL scores, which were better in patients selected for TTO. Six months after surgery, however, HRQL showed a greater deterioration after TTO than after TG in terms of role and social function, global quality of life and fatigue. Symptom scores for pain and diarrhoea increased in both groups. CONCLUSION: TTO had a greater negative impact on HRQL than TG for tumours of the gastro-oesophageal junction. PMID- 17849372 TI - GLYCAM06: a generalizable biomolecular force field. Carbohydrates. AB - A new derivation of the GLYCAM06 force field, which removes its previous specificity for carbohydrates, and its dependency on the AMBER force field and parameters, is presented. All pertinent force field terms have been explicitly specified and so no default or generic parameters are employed. The new GLYCAM is no longer limited to any particular class of biomolecules, but is extendible to all molecular classes in the spirit of a small-molecule force field. The torsion terms in the present work were all derived from quantum mechanical data from a collection of minimal molecular fragments and related small molecules. For carbohydrates, there is now a single parameter set applicable to both alpha- and beta-anomers and to all monosaccharide ring sizes and conformations. We demonstrate that deriving dihedral parameters by fitting to QM data for internal rotational energy curves for representative small molecules generally leads to correct rotamer populations in molecular dynamics simulations, and that this approach removes the need for phase corrections in the dihedral terms. However, we note that there are cases where this approach is inadequate. Reported here are the basic components of the new force field as well as an illustration of its extension to carbohydrates. In addition to reproducing the gas-phase properties of an array of small test molecules, condensed-phase simulations employing GLYCAM06 are shown to reproduce rotamer populations for key small molecules and representative biopolymer building blocks in explicit water, as well as crystalline lattice properties, such as unit cell dimensions, and vibrational frequencies. PMID- 17849374 TI - Nitric oxide synthase in critically ischaemic muscle and alterations in isoform expression during revascularization surgery. AB - BACKGROUND: Dysfunction of the nitric oxide pathway is implicated in peripheral arterial disease. Nitric oxide synthase (NOS) isoforms and NOS activity were studied in muscle from patients with critical leg ischaemia (CLI). Alterations in NOS during revascularization surgery were also assessed. METHODS: Muscle biopsies were taken from patients with CLI undergoing amputation and also from patients undergoing femorodistal bypass at the start of surgery, after arterial clamping and following reperfusion. The presence of NOS within muscle sections was confirmed using reduced nicotinamide adenine dinucleotide phosphate diaphorase histochemistry. NOS isoform distribution was studied by immunohistochemistry. NOS mRNA and protein levels were measured using real-time reverse transcriptase polymerase chain reaction and western blotting. NOS activity was assessed with the citrulline assay. RESULTS: All three NOS isoforms were found in muscle, associated with muscle fibres and microvessels. NOS I and III protein expression was increased in CLI (P = 0.041). During revascularization, further ischaemia and reperfusion led to a rise in NOS III protein levels (P = 0.008). NOS activity was unchanged. CONCLUSION: Alterations in NOS I and III occurred in muscle from patients with CLI and further changes occurred during bypass surgery. PMID- 17849375 TI - High-speed nanometer-scale imaging for studies of nanowire mechanics. PMID- 17849376 TI - Formation, structure, and polymorphism of novel lowest-dimensional AgI nanoaggregates by encapsulation in carbon nanotubes. PMID- 17849377 TI - Template synthesis of carbon nanotubes with diamond-shaped cross sections. PMID- 17849378 TI - Viability studies of pure carbon- and nitrogen-doped nanotubes with Entamoeba histolytica: from amoebicidal to biocompatible structures. PMID- 17849379 TI - DNA-regulated micro- and nanoparticle assembly. PMID- 17849381 TI - Apology. Hydrogen peroxide triggered prochelator activation, subsequent metal chelation, and attenuation of the Fenton reaction. PMID- 17849380 TI - Late gastrointestinal disorders after rectal cancer surgery with and without preoperative radiation therapy. AB - BACKGROUND: The aim of the study was to analyse late gastrointestinal disorders necessitating hospital admission following rectal cancer surgery and to determine their relationship to preoperative radiation therapy. METHODS: Curatively treated patients participating in the Swedish Rectal Cancer Trial during 1987-1990, randomized to preoperative irradiation (454 patients) or surgery alone (454), were matched against the Swedish Hospital Discharge Registry. Hospital records for patients admitted with gastrointestinal diagnoses were reviewed. RESULTS: Irradiated patients had an increased relative risk (RR) of late small bowel obstruction (RR 2.49 (95 per cent confidence interval (c.i.) 1.48 to 4.19)) and abdominal pain (RR 2.09 (95 per cent c.i. 1.03 to 4.24)) compared with patients treated by surgery alone. The risk of late small bowel obstruction requiring surgery was greatly increased (RR 7.42 (95 per cent c.i. 2.23 to 24.66)). Irradiated patients with postoperative anastomotic leakage were at increased risk for late small bowel obstruction (RR 2.99 (95 per cent c.i. 1.07 to 8.31)). The risk of small bowel obstruction was also related to the radiation technique and energy used. CONCLUSION: Small bowel obstruction is more common in patients with rectal cancer treated with preoperative radiation therapy. PMID- 17849383 TI - Statistical surveillance of epidemics: peak detection of influenza in Sweden. AB - A statistical surveillance system gives a signal as soon as data give enough evidence of an important event. We consider on-line surveillance systems for detecting changes in influenza incidence. One important feature of the influenza cycle is the start of the influenza season, and another one is the change to a decline (the peak). In this report we discuss statistical methods for on-line peak detection. One motive for doing this is the need for health resource planning. Surveillance systems were adapted for Swedish data on laboratory verified diagnoses of influenza. In Sweden, the parameters of the influenza cycles vary too much from year to year for parametric methods to be useful. We suggest a non-parametric method based on the monotonicity properties of the increase and decline around a peak. A Monte Carlo study indicated that this method has useful stochastic properties. The method was applied to Swedish data on laboratory verified diagnoses of influenza for seven periods. PMID- 17849384 TI - The log multinomial regression model for nominal outcomes with more than two attributes. AB - An estimate of the risk or prevalence ratio, adjusted for confounders, can be obtained from a log binomial model (binomial errors, log link) fitted to binary outcome data. We propose a modification of the log binomial model to obtain relative risk estimates for nominal outcomes with more than two attributes (the "log multinomial model"). Extensive data simulations were undertaken to compare the performance of the log multinomial model with that of an expanded data multinomial logistic regression method based on the approach proposed by Schouten et al. (1993) for binary data, and with that of separate fits of a Poisson regression model based on the approach proposed by Zou (2004) and Carter, Lipsitz and Tilley (2005) for binary data. Log multinomial regression resulted in "inadmissable" solutions (out-of-bounds probabilities) exceeding 50% in some data settings. Coefficient estimates by the alternative methods produced out-of-bounds probabilities for the log multinomial model in up to 27% of samples to which a log multinomial model had been successfully fitted. The log multinomial coefficient estimates generally had lesser relative bias and mean squared error than the alternative methods. The practical utility of the log multinomial regression model was demonstrated with a real data example. The log multinomial model offers a practical solution to the problem of obtaining adjusted estimates of the risk ratio in the multinomial setting, but must be used with some care and attention to detail. PMID- 17849385 TI - Inference methods for the conditional logistic regression model with longitudinal data. AB - This paper considers inference methods for case-control logistic regression in longitudinal setups. The motivation is provided by an analysis of plains bison spatial location as a function of habitat heterogeneity. The sampling is done according to a longitudinal matched case-control design in which, at certain time points, exactly one case, the actual location of an animal, is matched to a number of controls, the alternative locations that could have been reached. We develop inference methods for the conditional logistic regression model in this setup, which can be formulated within a generalized estimating equation (GEE) framework. This permits the use of statistical techniques developed for GEE-based inference, such as robust variance estimators and model selection criteria adapted for non-independent data. The performance of the methods is investigated in a simulation study and illustrated with the bison data analysis. PMID- 17849386 TI - Adjusting nonresponse bias at subdomain levels using multiple response phases. AB - When a sampling unit doesn't respond to a survey it is termed unit nonresponse. Unit nonresponse may have a dramatic affect on estimation results of interest. Using only those who responded to the survey to calculate the estimate may bias the estimate, known as nonresponse bias. Many approaches have been created in order to account for nonresponse. One such approach is to resample those nonrespondents in a second response "phase" (or more). We build a Bayesian hierarchical model that uses information from multiple response "phases" to estimate the phase specific response rates from I subdomains. This information is simultaneously used to estimate the success rates in those I subdomains. Conditional success rates are then estimated for the first phase respondents, second phase respondents, and nonrespondents (the third response phase). A relationship between these three sets of conditional success rates is incorporated into the model. This is done through a spatially dependent structure. The 1998 Missouri Turkey Hunting Survey is used to illustrate this methodology. The success rate estimates from nonrespondents have a significant impact on the overall success rate. PMID- 17849388 TI - Accurate prediction of protonation state as a prerequisite for reliable MM PB(GB)SA binding free energy calculations of HIV-1 protease inhibitors. AB - Binding free energies were calculated for the inhibitors lopinavir, ritonavir, saquinavir, indinavir, amprenavir, and nelfinavir bound to HIV-1 protease. An MMPB/SA-type analysis was applied to conformational samples from 3 ns explicit solvent molecular dynamics simulations of the enzyme-inhibitor complexes. Binding affinities and the sampled conformations of the inhibitor and enzyme were compared between different HIV-1 protease protonation states to find the most likely protonation state of the enzyme in the complex with each of the inhibitors. The resulting set of protonation states leads to good agreement between calculated and experimental binding affinities. Results from the MMPB/SA analysis are compared with an explicit/implicit hybrid scheme and with MMGB/SA methods. It is found that the inclusion of explicit water molecules may offer a slight advantage in reproducing absolute binding free energies while the use of the Generalized Born approximation significantly affects the accuracy of the calculated binding affinities. PMID- 17849391 TI - Theoretical elucidation of the rhodium-catalyzed [4 + 2] annulation reactions. AB - The reaction mechanism of the Rh-catalyzed [4 + 2] annulation of 4-alkynals with isocyanates is unraveled using density functional calculations. The reaction mechanisms of the model system and the real substituted system have been investigated and the results are compared. From our theoretical results based on the model and real substituted system, it is shown that (a) the rate-determining step is the Rh-H addition to the alkyne, (b) the formation of the cyclopentenone G and glutarimide K represents a severe competition, and (c) the product selectivity should be controlled by the amount of the isocyanates. In addition, it is demonstrated that there exist steric effects in the real substituted system, but missed in model system. Our calculations also show that although the results obtained on the model system could explain the mechanism in principle, the real substituted system could reflect the mechanism more exactly and make the reaction proceed with regioselectivity. PMID- 17849392 TI - cclib: a library for package-independent computational chemistry algorithms. AB - There are now a wide variety of packages for electronic structure calculations, each of which differs in the algorithms implemented and the output format. Many computational chemistry algorithms are only available to users of a particular package despite being generally applicable to the results of calculations by any package. Here we present cclib, a platform for the development of package independent computational chemistry algorithms. Files from several versions of multiple electronic structure packages are automatically detected, parsed, and the extracted information converted to a standard internal representation. A number of population analysis algorithms have been implemented as a proof of principle. In addition, cclib is currently used as an input filter for two GUI applications that analyze output files: PyMOlyze and GaussSum. PMID- 17849393 TI - High-spin versus broken symmetry-Effect of DFT spin density representation on the geometries of three diiron (III) model compounds. AB - Unrestricted density functional theory calculations have been conducted on three diiron(III) synthetic model compounds containing antiferromagnetically coupled high-spin (HS) irons for which crystallographic structures and Raman spectral data are available. Three density functionals have been employed: BPW91, PWC, and BOP. The study compares the effects on optimized geometries and harmonic vibrational frequencies of spin-paired (SP) low-spin, HS, and broken symmetry antiferromagnetically coupled singlet representations of the spin density distribution. The geometries around the diiron centers in the HS and broken symmetry (BS) representations are found to be similar, both markedly different from those arising from the SP representation. Small differences between the HS and BS results are seen in bond lengths, angles, Raman frequencies, and spin densities associated with oxo and peroxo bridges between the irons. PMID- 17849394 TI - Effects of long-range electrostatic forces on simulated protein folding kinetics. AB - Molecular dynamics simulations are a useful tool for characterizing protein folding pathways. There are several methods of treating electrostatic forces in these simulations with varying degrees of physical fidelity and computational efficiency. In this article, we compare the reaction field (RF) algorithm, particle-mesh Ewald (PME), and tapered cutoffs with increasing cutoff radii to address the impact of the electrostatics method employed on the folding kinetics. We quantitatively compare different methods by a correlation of quantitative measures of protein folding kinetics. The results of these comparisons show that for protein folding kinetics, the RF algorithm can quantitatively reproduce the kinetics of the more costly PME algorithm. These results not only assist the selection of appropriate algorithms for future simulations, but also give insight on the role that long-range electrostatic forces have in protein folding. PMID- 17849395 TI - Intent to harm or injure? Gender and the expression of anger. AB - Gender differences in aggressive behaviour but not in anger suggest that women may express anger through behaviours that lack intent to harm or injure. Angry behaviours (injurious and noninjurious) were rated in terms of their likelihood of use when angry (N=888). Confirmatory factor analysis revealed a direct aggression factor and two further scales: explosive acts (e.g. throwing objects when alone) and defusing acts (e.g. talking to a third party). Men exceeded women on direct aggression and explosive acts, whereas women exceeded men on defusing acts. Expressive beliefs about aggression (as a loss of self-control) were higher among women and strongly associated with use of defusing acts and the avoidance of direct aggression. Instrumental beliefs about aggression (as a means of control over others) were higher among men and showed the opposite pattern of associations. We highlight the need for further work on actors' intention in relation to angry behaviours and the impact of context on these intentions. PMID- 17849398 TI - Homology modeling of NR2B modulatory domain of NMDA receptor and analysis of ifenprodil binding. AB - NMDA receptors are glutamate-gated ion channels (iGluRs) that are involved in several important physiological functions such as neuronal development, synaptic plasticity, learning, and memory. Among iGluRs, NMDA receptors have been perhaps the most actively investigated for their role in chronic neurodegeneration such as Alzheimer's, Parkinson's, and Huntington's diseases. Recent studies have shown that the NTD of subunit NR2B modulates ion channel gating through the binding of allosteric modulators such as the prototypical compound ifenprodil. In the present paper, the construction of a three-dimensional model for the NR2B modulatory domain is described and docking calculations allow, for the first time, definition of the ifenprodil binding pose at an atomic level and fully explain all the available structure-activity relationships. Moreover, in an attempt to add further insight into the ifenprodil mechanism of action, as it is not completely clear if it binds and stabilizes an open or a closed conformation of the NR2B modulatory domain, a matter, which is fundamental for the rational design of NMDA antagonists, MD simulations followed by an MM-PBSA analysis were performed. These calculations reveal that the closed conformation of the R1-R2 domain, rather than the open, constitutes the high affinity binding site for ifenprodil and that a profound stabilization of the closed conformation upon ifenprodil binding occurs. Thus, for a rational design and/or for virtual screening experiments, the closed conformation of the R1-R2 domain should be taken into account and our 3D model can provide valuable hints for the design of NR2B-selective antagonists. PMID- 17849399 TI - Synthesis of conformationally constrained glutamic acid homologues and investigation of their pharmacological profiles. AB - Homologation of the glutamic acid chain together with conformational constraint is a commonly used strategy to achieve selectivity towards different types of glutamate receptors. We investigated the effects of a further increase in the distance between the amino acid moiety and the distal carboxylate group of model compounds (+/-)-1 and (+/-)-2 on their activity/selectivity profiles. We therefore synthesized new derivatives (+/-)-3-(+/-)-6, which are homologues of glutamic acid containing three additional carbon units. Moreover, because the potency of NMDA antagonists can be markedly increased by replacing the distal carboxylate with the bioisosteric phosphonate group, we also prepared the corresponding phosphonate derivatives (+/-)-7-(+/-)-10. All new compounds were submitted to binding assays with iGluRs, and derivatives (+/-)-3-(+/-)-6 were also tested in second messenger assays at representative mGluR subtypes. All the applied structural modifications were detrimental to the interaction with NMDA receptors. Conversely, structural variation of the nonselective mGluR ligand (+/ )-2 led to derivative (+/-)-5, which behaved as a selective group I metabotropic receptor antagonist. Notably, upon i.c.v. administration in DBA/2 mice, amino acid (+/-)-5 produced a significant protection against audiogenic seizures, whereas it was inactive after i.p. administration. PMID- 17849400 TI - Medicinal chemistry in parasitology: new avenues in drug discovery. PMID- 17849401 TI - Nickel-catalyzed Mizoroki-Heck- versus Michael-type addition of organoboronic acids to alpha,beta-unsaturated alkenes through fine-tuning of ligands. AB - Various arylboronic acids reacted with activated alkenes in the presence of [Ni(dppe)Br2], ZnCl2, and H2O in CH3CN at 80 degrees C to give the corresponding Mizoroki-Heck-type addition products in good to excellent yields. Furthermore, 1 equivalent of the hydrogenation product of the activated alkene was also produced. By tuning the ligands of the nickel complexes and the reaction conditions, Michael-type addition was achieved in a very selective manner. Thus, various p- and o-substituted arylboronic acids or alkenylboronic acid reacted smoothly with activated alkenes in CH3CN at 80 degrees C for 12 h catalyzed by Ni(acac)2, P(o-anisyl)3, and K2CO3 to give the corresponding Michael-type addition products in excellent yields. However, for m-substituted arylboronic acids, the yields of Michael-type addition products are very low. The cause of this unusual meta-substitution effect is not clear. By altering the solvent or phosphine ligand, the product yields for m-substituted arylboronic acids were greatly improved. In contrast to previous results in the literature, the present catalytic reactions required water for Mizoroki-Heck-type products and dry reaction conditions for Michael-type addition products. Possible mechanistic pathways for both addition reactions are proposed. PMID- 17849402 TI - Tunable bacterial agglutination and motility inhibition by self-assembled glyco nanoribbons. AB - We explored a method of controlling bacterial motility and agglutination by using self-assembled carbohydrate-coated beta-sheet nanoribbons. To this aim, we synthesized triblock peptides that consist of a carbohydrate, a polyethylene glycol (PEG) spacer, and a beta-sheet-forming peptide. An investigation into the effect of PEG-spacer length on the self-assembly of the triblock peptides showed that the PEG should be of sufficiently length to stabilize the beta-sheet nanoribbon structure. It was found that the stabilization of the nanoribbon led to stronger activity in bacterial motility inhibition and agglutination, thus suggesting that antibacterial activity can be controlled by the stabilization strategy. Furthermore, another level of control over bacterial motility and agglutination was attained by co-assembly of bacteria-specific and -nonspecific supramolecular building blocks. The nanoribbon specifically detected bacteria after the encapsulation of a fluorescent probe. Moreover, the detection sensitivity was enhanced by the formation of bacterial clusters. All these results suggest that the carbohydrate-coated beta-sheet nanoribbons can be developed as promising agents for pathogen capture, inactivation, and detection, and that the activity can be controlled at will. PMID- 17849403 TI - Unusual coexistence of magnetic and nonmagnetic Mo6 octahedral clusters in a chalcohalide solid solution: synthesis, X-ray diffraction, EPR, and DFT investigations of Cs3Mo6Ii6Ii2-xSeixIa6. AB - The Cs3Mo6Ii6Ii2-xSeixIa6 series has been obtained by a solid-state route. There is evidence for a solid solution between the compositions Cs3Mo6Ii6Ii0.8Sei1.2Ia6 and Cs3Mo6Ii6Ii0.4Sei1.6Ia6 (space group: R3c, Z=6; a=16.7065(4), c=20.5523(4) A, V=4967.8(2) A3 and a=16.6354(3), c=20.5444(4) A, V=4923.7(2) A3, respectively). The structure of this new series is based on magnetic [Mo6Ii6Sei2Ia6]3- and diamagnetic [Mo6Ii7SeiIa6]3- units with 23 and 24 valence electrons per Mo6 cluster, respectively. For a particular x, the structure of Cs3Mo6Ii6Ii2-xSexIa6 is based on a mixture of (x-1) [Mo6Ii6Sei2Ia6]3- with (2-x) [Mo6Ii7SeiIa6]3-. This leads to an average [Mo6Ii6Ii2-xSexIa6]3- ionic unit deduced from single crystal X-ray diffraction investigations. The two inner positions of the average face-capped [Mo6Ii8-xSeixIa6]3- ionic units (located on the threefold axis of the unit) are randomly occupied by iodine and selenium, whereas the other ligand positions are fully occupied by iodine. Low-temperature electron paramagnetic resonance (EPR) studies reveal a signal split into two components with g||>gperpendicular. The reciprocal double integration intensity of the EPR signal versus T graph reveals a typical Curie law behavior. A density functional theory (DFT) study indicates that occupation of the inner position on the threefold axis by selenium atoms is preferred energetically among the three possible distributions of selenium atoms. The comparison of experimental and theoretical g values confirms the crystallographic analysis and agrees with the axial elongation of the Mo6 cluster within the crystal structure. PMID- 17849404 TI - Copper-catalyzed asymmetric conjugate addition of trialkylaluminium reagents to trisubstituted enones: construction of chiral quaternary centers. AB - Me3Al, Et3Al, and vinylalane species undergo enantioselective conjugate addition to a wide range of 2- or 3-substituted enones (cyclopent-2-enones, cyclohex-2 enones, 3-methyl cyclohept-2-enone) in the presence of catalytic amount of copper salt (copper thiophene carboxylate, [Cu(CH3CN)4]BF4 or [CuOTf]2C6H6) and tropos phosphoramidite-based ligand. Thus, chiral quaternary centers can be built, with up to 98% ee after rigorous optimization of experimental conditions. It was shown that the main important parameter was the order of the introduction of the reagents. Then, the generated enantioenriched aluminium enolates and the chiral conjugate adducts were functionalized and used for subsequent reactions. PMID- 17849405 TI - Ultrafast coelectrophoretic fluorescent staining of proteins with carbocyanines. AB - Protein detection on SDS gels or on 2-D gels must combine several features, such as sensitivity, homogeneity from one protein to another, speed, low cost, and user-friendliness. For some applications, it is also interesting to have a nonfixing stain, so that proteins can be mobilized from the gel for further use (electroelution, blotting). We show here that coelectrophoretic staining by fluorophores of the oxacarbocyanine family, and especially diheptyloxacarbocyanine, offers several positive features. The sensitivity is intermediate between the one of colloidal CBB and the one of fluorescent ruthenium complexes. Detection is achieved within 1 h after the end of the electrophoretic process and does not use any fixing or toxic agent. The fluorescent SDS-carbocyanine-protein complexes can be detected either with a laser scanner with an excitation wavelength of 488 nm or with a UV table operating at 302 nm. Excellent sequence coverage in subsequent MS analysis of proteolytic peptides is also achieved with this detection method. PMID- 17849406 TI - The salivary glands and saliva of Anopheles gambiae as an essential step in the Plasmodium life cycle: a global proteomic study. AB - Proteins synthesized in the salivary glands of the Anopheles gambiae mosquito are thought to be important in the life cycle of the malaria parasite Plasmodium. To describe A. gambiae salivary gland and saliva contents, we combined several techniques: 1-DE, 2-DE and LC MS/MS. This study has identified five saliva proteins and 122 more proteins from the salivary glands, including the first proteomic description for 89 of these salivary gland proteins. Since the invasion and sporozoite maturation take place during the process of salivary glands ageing, the effect of salivary gland age on salivary component composition was examined. LC MS/MS profiling of young versus old salivary gland proteomes suggests that there is an over-representation of proteins involved in signaling and proteins related to the immune response in the proteins from older mosquitoes. The iTRAQ labeling was used for a comparative proteomic analysis of salivary gland samples from infected or Plasmodium berghei-free mosquitoes. The expression levels of five secreted proteins were altered when the parasite was present. These observations will serve as a basis for future work concerning the possible role of these proteins in the interaction between A. gambiae, Plasmodium and the mammalian host. PMID- 17849407 TI - Comparative proteomic analysis of myotube caveolae after milli-calpain deregulation. AB - Caveolae are specialised RAFTs (detergent-resistant membrane microdomains enriched in cholesterol and glycosphingolipids). Caveolin, the main caveolae protein, is essential to the organisation of proteins and lipids, and interacts with numerous mediating proteins through a 'Caveolin Scalfolding Domain'. Consequently, caveolae play a major role in signal transduction and appear to be veritable signalling platforms. In muscle cells, caveolae are essential for fusion and differentiation, and are also implicated in a type of muscular dystrophy (LGMD1C). In a preceding work, we demonstrated the presence of active milli-calpain (m-calpain) in myotube caveolae. Calpains are calcium-dependent proteases involved in several cellular processes, including myoblast fusion and migration, PKC-mediated intracellular signalling and remodelling of the cytoskeleton. For the first time, we have proved the cholesterol-dependent localisation of m-calpain in the caveolae of C(2)C(12) myotubes. Calpain dependent caveolae involvement in myoblast fusion was also strongly suggested. Furthermore, eight differentially expressed caveolae associated proteins were identified by 2-DE and LC-MS/MS analyses using an m-calpain antisense strategy. This proteomic study also demonstrates the action of m-calpain on vimentin, desmin and vinculin in myotube caveolae and suggests m-calpain's role in several mitochondrial pathways. PMID- 17849408 TI - Proteomic approach to studying the cytotoxicity of YC-1 on U937 leukemia cells and antileukemia activity in orthotopic model of leukemia mice. AB - To evaluate the effects of YC-1 on leukemia cell lines, PI incorporation was used to determine cell viability. YC-1 induced a dose- and time-dependent decrease in viability and apoptosis in YC-1-treated U937 cells. YC-1-induced apoptosis is a cyclic guanosine monophosphate (cGMP)-independent pathway. Proteomic analysis showed that the altered proteins include the significant regulation of HSP70, chaperonin, ATP synthase beta chains, and Chain F. Western blotting and immuno cytochemistry stain showed that YC-1 treatment caused a time-dependent increase in cytosolic Cytochrome c, pro-caspase-9, Apaf-1, and the activation of caspase-9 and -3. Importantly, the in vivo antileukemia effects of YC-1 were evaluated in BALB/c mice inoculated with WEHI-3B orthotopic model. YC-1 enhanced survival rate and prevented the body weight loss in leukemia mice. The enlargement of spleen and lymph nodes were reduced in YC-1 treated than that in leukemia mice. H-E stain of spleen sections revealed that infiltration of immature myeloblastic cells into red pulp was reduced in YC-1-treated group. The apoptotic cells of splenocyte were significantly increased in YC-1 treated than that in leukemia mice by Tdt-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. Taken together, we conclude that YC-1 acted against U937 cells in vitro via a mitochondrial-dependent apoptosis pathway, and in orthotopic leukemia model, YC-1 administered antileukemia activity. PMID- 17849409 TI - Identification of novel bacterial plasminogen-binding proteins in the human pathogen Mycobacterium tuberculosis. AB - Binding and activation of human plasminogen (Plg) to generate the proteolytic enzyme plasmin (Plm) have been associated with the invasive potential of certain bacteria. In this work, proteomic analysis together with ligand blotting assays identified several major Plg-binding spots in Mycobacterium tuberculosis soluble extracts (SEs) and culture filtrate proteins. The identity of 15 different proteins was deduced by N-terminal and/or MS and corresponded to DnaK, GroES, GlnA1, Ag85 complex, Mpt51, Mpt64, PrcB, MetK, SahH, Lpd, Icl, Fba, and EF-Tu. Binding of Plg to recombinant M. tuberculosis DnaK, GlnA1, and Ag85B was further confirmed by ELISA and ligand blotting assays. The binding was inhibited by epsilon-aminocaproic acid, indicating that the interaction involved lysine residues. Plg bound to recombinant mycobacterial proteins was activated to Plm by tissue-type Plg activator. In contrast with recombinant proteins, M. tuberculosis SE enhanced several times the Plg activation mediated by the activator. Interestingly, GlnA1 was able to bind the extracellular matrix (ECM) protein fibronectin. Together these results show that M. tuberculosis posses several Plg receptors suggesting that bound Plg to bacteria surface, can be activated to Plm, endowing bacteria with the ability to break down ECM and basal membranes proteins contributing to tissue injury in tuberculosis. PMID- 17849410 TI - Novel identification of expressed genes and functional classification of hypothetical proteins from Neisseria meningitidis serogroup A. AB - To implement the 2-DE database of serogroup A Neisseria meningitidis (MenA) and improve its potential of investigation in bacterial biology, cell extracts were separated by tricine-SDS-PAGE and 131 novel proteins were identified by microLC ESI-IT-MS/MS. These identifications extended to 404, the number of MenA gene expression products characterized at the proteome level, approximately covering 20% of the total ORFs predicted from genome sequence. This technical approach was particularly useful in ascertaining expression of ribosomal as well as hypothetical proteins. Particular attention was paid to functional characterization of hypothetical proteins by means of software analyses and database searches. PMID- 17849411 TI - A comparative proteomic approach to understand the adaptations of an H+ -ATPase defective mutant of Corynebacterium glutamicum ATCC14067 to energy deficiencies. AB - F172-8, an H(+)-ATPase-defective mutant of the glutamic acid-producing bacterium Corynebacterium glutamicum ATCC 14067, exhibits enhanced rates of glucose consumption and respiration compared to the parental strain when cultured in a biotin-rich medium with glucose as the carbon source. We conducted a comparative proteomic analysis to clarify the mechanism by which the enhanced glucose metabolism in this mutant is established using a proteome reference map for strain ATCC 14067. A comparison of the proteomes of the two strains revealed the up-regulated expression of the several important enzymes such as pyruvate kinase (Pyk), malate:quinone oxidoreductase (Mqo), and malate dehydrogenase (Mdh) in the mutant. Because Pyk activates glycolysis in response to cellular energy shortages in this bacterium, its increased expression may contribute to the enhanced glucose metabolism of the mutant. A unique reoxidation system has been suggested for NADH in C. glutamicum consisting of coupled reactions between Mqo and Mdh, together with the respiratory chain; therefore, the enhanced expression of both enzymes might contribute to the reoxidation of NADH during increased respiration. The proteomic analysis allowed the identification of unique physiological changes associated with the H(+)-ATPase defect in F172-8 and contributed to the understanding of the adaptations of C. glutamicum to energy deficiencies. PMID- 17849412 TI - Proteomic analysis of rice (Oryza sativa) seeds during germination. AB - Although seed germination is a major subject in plant physiological research, there is still a long way to go to elucidate the mechanism of seed germination. Recently, functional genomic strategies have been applied to study the germination of plant seeds. Here, we conducted a proteomic analysis of seed germination in rice (Oryza sativa indica cv. 9311) - a model monocot. Comparison of 2-DE maps showed that there were 148 proteins displayed differently in the germination process of rice seeds. Among the changed proteins, 63 were down regulated, 69 were up-regulated (including 20 induced proteins). The down regulated proteins were mainly storage proteins, such as globulin and glutelin, and proteins associated with seed maturation, such as "early embryogenesis protein" and "late embryogenesis abundant protein", and proteins related to desiccation, such as "abscisic acid-induced protein" and "cold-regulated protein". The degradation of storage proteins mainly happened at the late stage of germination phase II (48 h imbibition), while that of seed maturation and desiccation associated proteins occurred at the early stage of phase II (24 h imbibition). In addition to alpha-amylase, the up-regulated proteins were mainly those involved in glycolysis such as UDP-glucose dehydrogenase, fructokinase, phosphoglucomutase, and pyruvate decarboxylase. The results reflected the possible biochemical and physiological processes of germination of rice seeds. PMID- 17849413 TI - Uniform nanostructured arrays of sodium rare-earth fluorides for highly efficient multicolor upconversion luminescence. PMID- 17849414 TI - Synthesis and characterization of chiral periodic mesoporous organosilicas. PMID- 17849416 TI - Corticosterone induces steroidogenic lesion in cultured adult rat Leydig cells by reducing the expression of star protein and steroidogenic enzymes. AB - The present study was designed to investigate the dose-dependent direct effect of corticosterone on adult rat Leydig cell steroidogenesis in vitro. Leydig cells were isolated from the testis of normal adult male albino rats, purified on discontinuous Percoll gradient and plated in culture plates/flasks overnight at 34 degrees C in a CO(2) incubator under 95% air and 5% CO(2) using DME/F12 medium containing 1% fetal bovine serum. After the attachment of cells, serum-containing medium was removed and cells were exposed to different doses (0, 50, 100, 200, 400, and 800 nM) of corticosterone using serum-free fresh medium for 24 h at 34 degrees C. At the end of exposure period, cells were utilized for assessment of the activities and mRNA expression of steroidogenic enzymes (cytochrome P(450) side chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase, 17beta hydroxysteroid dehydrogenase, and cytochrome P(450) aromatase) and steroidogenic acute regulatory protein gene expression. Testosterone and estradiol production were also quantified. Activities of cytochrome P(450) side chain cleavage enzyme, 3beta- and 17beta-hydroxysteroid dehydrogenases were declined significantly in a dose-dependent manner after corticosterone exposure, while their mRNA expression were significantly reduced at higher doses of corticosterone exposure. The activity and mRNA expression of cytochrome P(450) aromatase registered a significant increase at 100 nM dose of corticosterone whereas at 200-800 nM doses both the activity as well as the mRNA levels was significantly reduced below the basal level. StAR protein gene expression was significantly inhibited by higher doses of corticosterone employed. At all doses employed, corticosterone significantly reduced the production of testosterone by Leydig cells, while estradiol level registered a significant increase at 50 and 100 nM doses but at higher doses, it registered a significant decrease when compared to basal level. It is concluded from the present in vitro study that the molecular mechanism by which corticosterone reduces the production of Leydig cell testosterone is by reducing the activities and mRNA expression of steroidogenic enzymes and steroidogenic acute regulatory protein. PMID- 17849415 TI - Catalytic enantioselective alpha-acylvinyl anion reactions of silyloxyallenes. PMID- 17849418 TI - The generalizability of the Buss-Perry Aggression Questionnaire. AB - Aggressive and hostile behaviours and anger constitute an important problem across cultures. The Buss-Perry Aggression Questionnaire (AQ), a self-rating scale was published in 1992, and has quickly become the gold-standard for the measurement of aggression. The AQ scale has been validated extensively, but the validation focused on various narrowly selected populations, typically, on samples of college students. Individuals, however, who are at risk of displaying aggressive and hostile behaviours may come from a more general population. Therefore, it is important to investigate the scale's properties in such a population. The objective of this study was to examine the factorial structure and the psychometric properties of the AQ scale in a nationally representative sample of the Hungarian adult population.A representative sample of 1200 subjects was selected by a two-step procedure. The dimensionality and factorial composition of the AQ scale was investigated by exploratory and confirmatory factor analyses. Since spurious associations and increased factorial complexity can occur when the analysis fails to consider the inherently categorical nature of the item level data, this study, in contrast to most previous studies, estimated the correlation matrices subjected to factor analysis using the polychoric correlations. The resulting factors were validated via sociodemographic characteristics and psychopathological scales obtained from the respondents. The results showed that based on the distribution of factor loadings and factor correlations, in the entire nationally representative sample of 1200 adult subjects, from the original factor structure three of the four factors (Physical and Verbal Aggression and Hostility) showed a good replication whereas the fourth factor (Anger) replicated moderately well. Replication further improved when the sample was restricted in age, i.e. the analysis focused on a sample representing the younger age group, comparable to that used in the original Buss-Perry study. Similar to the Buss-Perry study, and other investigations of the AQ scale, younger age and male gender were robustly related to physical aggression. In addition, level of verbal aggression was different between the two genders (with higher severity in males) whereas hostility and anger were essentially the same in both genders.In conclusion, the current study based on a representative sample of adult population lends support to the use of the AQ scale in the general population. The authors suggest to exclude from the AQ the two inverse items because of the low reliability of these items with regard to their hypothesized constructs. PMID- 17849419 TI - HDAC3 overexpression and colon cancer cell proliferation and differentiation. AB - An immunohistochemical analysis of human colorectal adenocarcinomas showed that cancer cells express widely varying levels of HDAC3. The SW480 colon cancer cell line was found to express high levels of HDAC3 compared to other colon cancer cell lines. p21 was poorly induced in SW480 cells relative to the lower HDAC3 expressing HT-29 cells. RNAi-induced reduction of HDAC3 in SW480 cells increased their constitutive, butyrate-, TSA-, and TNF-alpha-induced expression of p21, but did not cause all the gene expression changes induced upon general histone deacetylase (HDAC) inhibition. SW480 cells with lower HDAC3 expression appeared to be poised for gene expression responses with increased histone H4-K12 acetylation, but not K5, K8, or K16 acetylation. Even though p21 was readily activated in HT29 cells, HDAC3 siRNA nonetheless stimulated p21 expression in these cells to a greater degree than HDAC1 and HDAC2 siRNA. SW480 cells with lower HDAC3 levels displayed an enhanced cell cycle arrest and growth inhibition by butyrate, but without changes in apoptosis or sensitivity to chemotherapeutic agents. As reported for other colon cancer cell lines, butyrate induced the rapid downregulation of the secretory cell differentiation markers mucin 2 and intestinal trefoil factor in SW480 cells. Interestingly, selective HDAC3 inhibition was sufficient to downregulate these genes. Our data support a central role for HDAC3 in regulating the cell proliferation and differentiation of colon cancer cells and suggest a potential mechanism by which colon cancers may become resistant to luminal butyrate. PMID- 17849420 TI - Reduced expression of the Rassf1a gene and its aberrant DNA methylation in pancreatic duct adenocarcinomas induced by N-nitrosobis(2-oxopropyl)amine in hamsters. AB - Alterations of the Rassf1a gene were investigated in pancreatic duct adenocarcinomas (PDAs) induced by N-nitrosobis(2-oxopropyl)amine (BOP) in hamsters. Female Syrian golden hamsters received 70 mg/kg BOP, followed by repeated exposures to an augmentation pressure regimen consisting of a choline deficient diet combined with a sequential course of DL-ethionine, L-methionine, and 20 mg/kg BOP. A total of 15 PDAs were obtained, and total RNAs were assessed by real-time quantitative reverse transcription (RT)-polymerase chain reaction (PCR). Expression of the Rassf1a was significantly reduced in PDAs (P < 0.005) compared with normal pancreatic tissues. For analysis of methylation status, bisulfite sequencing was performed. Normal tissues were all unmethylated in the 5' upstream region of Rassf1a. In contrast, four PDAs were highly methylated, correlating with reduced expression of the Rassf1a gene. Using reverse transcription (RT)-polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis, mutations were detected in 3 out of 15 PDAs (20%). These results suggested that alterations of the Rassf1a gene may be involved in development of PDAs induced by BOP in hamsters. PMID- 17849421 TI - Independent activation of Akt and NF-kappaB pathways and their role in resistance to TNF-alpha mediated cytotoxicity in gliomas. AB - Tumor associated macrophages (TAMs) constitute a substantial mass in gliomas. The activated macrophages secrete various cytokines that affect diverse functions of tumors. The aim of this study was to elucidate the role of Akt and NF-kappaB pathways in resistance to TNF-alpha mediated cell death in human gliomas using monolayers and multicellular spheroids (MCS) as in vitro models. Akt and NF kappaB are constitutively expressed and intimately involved in progression of gliomas. The activation of these pathways also renders the tumors resistant to conventional treatments including chemotherapy. While PI3K/Akt is shown to regulate the NF-kappaB activation in diverse systems, other studies place NF kappaB upstream of Akt activation. Using a stable IkappaBalpha mutant LN-18 cell line and pharmacological inhibitors to PI3K/Akt (LY294002) and Akt (Akt2), we provide evidence that Akt and NF-kappaB are activated independently on stimulation with TNF-alpha and both the pathways contribute towards resistance to TNF-alpha mediated cell death. TNF-alpha-induced NF-kappaB activation independent of PI3K/Akt pathway was also confirmed in human glioma cell lines-LN-229 and U373MG. We also show that NF-kappaB and Akt are activated during spheroidogenesis and their expression is further enhanced on stimulation with TNF-alpha implicating their involvement in resistance to cell death. The findings thus underscore the relevance of spheroids as appropriate in vitro models for studying the signaling pathways in drug induced resistance. PMID- 17849422 TI - PAX6 is expressed in pancreatic adenocarcinoma and is downregulated during induction of terminal differentiation. AB - Tumors of the exocrine pancreas are a major cause of cancer death and have among the poorest prognosis of any malignancy. Following the "cancer stem cell hypothesis," where tumors are believed to originate in tissue specific stem cells, we screened primary ductal pancreatic carcinomas and cell lines for the expression of possible stem cell factors. We find 32/46 (70%) of primary tumors and 9/10 (90%) of cell lines express PAX6. PAX6 is a transcription factor expressed throughout the pancreatic bud during embryogenesis but not in the mature exocrine pancreas. PAX proteins have also been implicated in maintaining stem cells in a committed but undifferentiated state but a role for PAX proteins in putative pancreas stem cells is not known. We induced a pancreatic carcinoma cell line, Panc-1, to differentiate by transfecting wild-type p53 and treating the cells with differentiation agents gastrin or butyrate. This treatment induces cells to terminally differentiate into a growth-arrested cell with neurite-like processes, express the terminal differentiation marker somatostatin and downregulate PAX6. This phenotype can be replicated by directly inhibiting PAX6 expression. These data support a model where PAX proteins are aberrantly expressed in tumors and downregulation leads to differentiation. PMID- 17849423 TI - Polymorphism of XRCC1 and the frequency of mutation in codon 249 of the p53 gene in hepatocellular carcinoma among Guangxi population, China. AB - In hepatocellular carcinoma (HCC), hotspot mutation in codon 249 of the p53 gene has been associated with exposure to aflatoxin B1 (AFB1). While the polymorphism of DNA repair gene X-ray repair cross-complementary group 1 (XRCC1) Arg399Gln may be related with AFB1-DNA adducts and gene mutations. Five hundred one HCCs were included in this study to investigate the role of the XRCC1 codon 399 polymorphism on hotspot mutation in codon 249 of the p53 gene. The genotypes of XRCC1 codon 399 and p53 codon 249 were examined by PCR-RFLP. The HCC patients with XRCC1 genotypes with 399 Gln (namely: XRCC1-AG/GG) exhibited a significantly higher frequency of the p53 hotspot mutations in codon 249 than those with the wild-type homozygote of XRCC1 [namely: XRCC1-AA, adjusted odds ratio (OR) = 6.77, 95% confidence interval (CI) = 4.34-10.57]. Compared with those individuals who did express XRCC1-AA as reference (OR = 1), moreover, individuals featuring XRCC1 AG/GG and AFB1-DNA adducts did experience a significantly greater frequency of the hotspot mutation in codon 249 of the p53 gene (adjusted OR = 28.37, 95% CI = 13.19-61.02, P < 0.01). This study suggests that the XRCC1 Arg399Gln polymorphism and AFB1-DNA adducts are associated with the increased frequency of the p53 mutations in codon 249. PMID- 17849424 TI - Inducible nitric oxide synthase, nitrotyrosine and p53 mutations in the molecular pathogenesis of Barrett's esophagus and esophageal adenocarcinoma. AB - Nitric oxide (NO) has been implicated as a potential causative factor for endogenous p53 mutations in gastrointestinal malignancy. To investigate the role of NO in esophageal adenocarcinoma (EADC), we studied patterns of p53 mutations, expression of inducible nitric oxide synthase (iNOS) and the tissue accumulation of nitrotyrosine (NTS), a stable reaction product of NO and a marker for cellular protein damage, in human premalignant and malignant esophageal epithelia. Tissues were obtained from patients with gastroesophageal reflux disease (GERD)-induced esophagitis (n = 76), Barrett's esophagus (BE; n = 119) and primary EADC (n = 54). DNA sequencing was used to characterize p53 mutations, RT-PCR to study iNOS mRNA expression, and immunohistochemistry to study NTS. Relative to self-matched normal epithelia, a progressive increase in iNOS mRNA expression was seen in GERD (30%; 23/76), BE (48%; 57/119), and EADC (63%; 34/54) tissues (P < 0.001). Among patients with EADC, elevated levels of NTS immunoreactivity were more frequent in tumors with p53 mutations (11/21; 52%) compared with tumors with wild-type p53 (9/33; 27%; P = 0.063), and specifically in tumors with p53 mutations at CpG dinucleotides (10/12; 83%) compared with non-CpG p53 mutations (1/9; 11%; P = 0.008). The increasing frequency of iNOS (mRNA) overexpression in GERD, BE and EADC supports the hypothesis that an active inflammatory process, most likely a consequence of GERD, underlies molecular progression to EADC. The highly significant association between NTS, reflecting chronic NO-induced cellular protein damage, and endogenous p53 mutations at CpG dinucleotides, provides further evidence for a molecular link between chronic inflammation and esophageal malignancy. PMID- 17849425 TI - Phase 1 study of tipifarnib in combination with imatinib for patients with chronic myelogenous leukemia in chronic phase after imatinib failure. AB - BACKGROUND: The tolerability and efficacy of the combination of tipifarnib, an orally bioavailable nonpeptidomimetic farnesyl transferase inhibitor, and imatinib was investigated in patients with chronic myelogenous leukemia in chronic phase who had failed imatinib. METHODS: Twenty-six patients (13 [50%] with Abl kinase domain mutations) were treated. The initial dose level was tipifarnib at a dose of 300 mg twice daily and imatinib at a dose of 300 mg daily. Therapy was escalated following a '3 + 3' phase 1 design and the maximum tolerated dose was defined as tipifarnib at a dose of 400 mg twice daily and imatinib at a dose of 400 mg daily. Therapy was administered for a median of 26 weeks (range, 3-150 weeks). RESULTS: Adverse events included diarrhea in 21 patients (81%) and nausea in 18 patients (69%), but were generally grade 2 or less (using the revised National Cancer Institute Common Toxicity Criteria). Grade 3-4 neutropenia and thrombocytopenia occurred in 11 patients (42%) and 8 patients (31%), respectively. Sixteen patients discontinued therapy (5 due to toxicity and 11 due to lack of response or disease progression). Hematologic responses were attained by 17 (68%) of 25 assessable patients. Nine patients (36%) also achieved a cytogenetic response (3 complete responses, 4 partial responses, and 2 minimal responses), including 4 patients harboring mutant Bcr Abl tyrosine kinases. One patient bearing the highly imatinib-resistant T315I mutant achieved a partial cytogenetic response. The median response duration was 3 months (range, 2-30+ months). CONCLUSIONS: The combination of tipifarnib and imatinib is well tolerated and has activity against several Abl kinase domain mutants. Combinations of tipifarnib with more potent tyrosine kinase inhibitors warrant further investigation. PMID- 17849426 TI - Food transfers to young and mates in wild owl monkeys (Aotus azarai). AB - Accounts of food sharing within natural populations of mammals have focused on transfers to offspring or transfers of food items that are difficult to obtain (such as meat). Five groups of socially monogamous owl monkeys (Aotus azarai azarai) in Formosa, Argentina were observed during 107 hr to determine the pattern of food sharing under natural conditions. There were a total of 42 social interactions involving food with food being transferred on eight occasions. Adult males transferred food to young more often than did adult females. All types of food that were readily obtained and eaten by all age/sex classes were transferred to young. Adult females also transferred food to their mates. This type of food sharing is very rare among animals and may have social benefits specific to monogamous mammals with paternal care. PMID- 17849427 TI - The hazards of intermediate endpoints. PMID- 17849428 TI - The spatial order of transcription in mammalian cells. AB - We have previously developed technology for multiplexing probes for the detection of transcription of many genes simultaneously within single cells. This has allowed us to determine the spatial localization of multiple genes with respect to each other in the nucleus, and ultimately the expression profile of the cell with respect to surrounding cells in a tissue. Six parameters of transcriptional organization in individual cells from culture and tissue were used to characterize significant differences in intracellular and intercellular expression patterns while preserving cellular morphology and histological context. We found that, unlike yeast, mammalian expression is excluded from the periphery and in addition, a subtle but complex organization underlies the transcriptional activity of these cells, both intra- and intercellularly. The approach has sufficient spatial resolution to be applied to the detection of chromosomal translocations or the identification of cancer cells. PMID- 17849429 TI - Expression of serum amyloid A transcripts in human bone tissues, differentiated osteoblast-like stem cells and human osteosarcoma cell lines. AB - Although the liver is the primary site of cytokine-mediated expression of acute phase serum amyloid A (SAA) protein, extrahepatic production has also been reported. Besides its role in amyloidosis and lipid homeostasis during the acute phase, SAA has recently been assumed to contribute to bone and cartilage destruction. However, expression of SAA in human osteogenic tissue has not been studied. Therefore, we first show that SAA1 (coding for the major SAA isoform) but not SAA2 transcripts are expressed in human trabecular and cortical bone fractions and bone marrow. Next, we show expression of (i) IL-1, IL-6, and TNF receptor transcripts; (ii) the human homolog of SAA-activating factor-1 (SAF-1, a transcription factor involved in cytokine-mediated induction of SAA genes); and (iii) SAA1/2 transcripts in non-differentiated and, to a higher extent, in osteoblast-like differentiated human mesenchymal stem cells. Third, we provide evidence that human osteoblast-like cells of tumor origin (MG-63 and SAOS-2) express SAF-1 under basal conditions. SAA1/2 transcripts are expressed under basal conditions (SAOS-2) and cytokine-mediated conditions (MG-63 and SAOS-2). RT PCR, Western blot analysis, and immunofluorescence technique confirmed cytokine mediated expression of SAA on RNA and protein level in osteosarcoma cell lines while SAA4, a protein of unknown function, is constitutively expressed in all osteogenic tissues investigated. PMID- 17849430 TI - Surface structural investigation of starch-based biomaterials. AB - Surface structural characterisation of three different starch-based blends (with poly[ethylene-co-(vinyl alcohol)], cellulose acetate and polycaprolactone) was carried out. The results show that there is a difference between the bulk and the surface composition of all studied blends. Two different hypotheses were investigated - predominant presence of a synthetic component on the surface and possible inter- and/or intramolecular bonds. The results were related to previous data for cell behaviour on those materials. It was found that both surface hydrophilicity and surface functionality are of great importance for cell adhesion and growth on starch-based biomaterials. PMID- 17849431 TI - Biodegradation of aliphatic and aromatic polycarbonates. AB - Polycarbonate is one of the most widely used engineering plastics because of its superior physical, chemical, and mechanical properties. Understanding the biodegradation of this polymer is of great importance to answer the increasing problems in waste management of this polymer. Aliphatic polycarbonates are known to biodegrade either through the action of pure enzymes or by bacterial whole cells. Very little information is available that deals with the biodegradation of aromatic polycarbonates. Biodegradation is governed by different factors that include polymer characteristics, type of organism, and nature of pretreatment. The polymer characteristics such as its mobility, tacticity, crystallinity, molecular weight, the type of functional groups and substituents present in its structure, and plasticizers or additives added to the polymer all play an important role in its degradation. The carbonate bond in aliphatic polycarbonates is facile and hence this polymer is easily biodegradable. On the other hand, bisphenol A polycarbonate contains benzene rings and quaternary carbon atoms which form bulky and stiff chains that enhance rigidity. Even though this polycarbonate is amorphous in nature because of considerable free volume, it is non-biodegradable since the carbonate bond is inaccessible to enzymes because of the presence of bulky phenyl groups on either side. In order to facilitate the biodegradation of polymers few pretreatment techniques which include photo oxidation, gamma-irradiation, or use of chemicals have been tested. Addition of biosurfactants to improve the interaction between the polymer and the microorganisms, and blending with natural or synthetic polymers that degrade easily, can also enhance the biodegradation. PMID- 17849432 TI - The Attempted and Actual Assault Scale (Attacks). AB - The Attempted and Actual Assault Scale (Attacks) was designed to record the nature and severity of inpatient assaults. To explore the psychometric properties of the Scale, a videotape of interpersonal assaults was compiled with clips from regular television broadcasts. During a meeting of the European Violence in Psychiatry Research Group (EVIPRG), 22 members from 14 different countries were instructed to rate the videotaped assaults on both the MOAS and the Attacks. Inter-rater reliability--in terms of intra-class correlation coefficients--was 0.70 for Attacks and 0.48 for MOAS severity scores. Attacks severity scores turned out to be significantly associated with the judgments of the raters about the severity of the observed assaults (Spearman's rho = 0.70). It is concluded that the psychometric properties of the newly developed Attacks are promising. PMID- 17849433 TI - Reducing the length of mental health instruments through structurally incomplete designs. AB - This paper presents structurally incomplete designs as an approach to reduce the length of mental health tests. In structurally incomplete test designs, respondents only fill out a subset of the total item set. The scores on the unadministered items are estimated using methods for missing data. As an illustration, structurally incomplete test designs recording, respectively, two thirds, one half, one third and one quarter of the complete item set were applied to item scores on the Centre of Epidemiological Studies-Depression (CES-D) scale of the respondents in the Longitudinal Aging Study Amsterdam (LASA). The resulting unobserved item scores were estimated with the missing data method Data Augmentation. The complete and reconstructed data yielded very similar total scores and depression classifications. In contrast, the diagnostic accuracy of the incomplete designs decreased as the designs had more unobserved item scores. The discussion addresses the strengths and limitations of the application of incomplete designs in mental health research. PMID- 17849434 TI - Rating catatonia in patients with chronic schizophrenia: Rasch analysis of the Bush-Francis Catatonia Rating Scale. AB - BACKGROUND: Catatonic signs and symptoms are frequently observed in patients with chronic schizophrenia. Clinical surveys have suggested that the composition of catatonic syndrome occurring in chronic schizophrenia may be different from what is found in acute psychiatric disorders or medical conditions. Consequently, this patient population may need tailor-made rating instruments for catatonia. The aim of the present study was to examine the suitability and accuracy of using the Bush-Francis Catatonia Rating Scale (BFCRS) in chronic schizophrenia inpatients. METHOD: The unidimensionality (optimal number of items; item fit), and the scoring scheme (the optimal number of scoring categories) of the BFCRS were determined in a random sample of 225 patients with chronic schizophrenia applying Rasch analysis. In addition, differential item functioning (DIF) analysis was also performed. RESULTS: The BFCRS proved to be unidimensional apart from three misfit and one marginally misfit items. The three misfit items were removed from the scale thereby constructing a revised version called BFCRS-R. Since the original BFCRS (BFCRS-O) showed no increase across items across steep gradients (poor endorsability of step calibrations), in BFCRS-R a binary scale ('absent' versus 'present' choices only) was constructed instead of the scoring scheme of 0 3. The 20-item BFCRS-R showed improved psychometric properties in that it had a higher item separation index than BFCRS-O. BFCRS-R mean logit was closer to zero indicating that the items on the scale and the subjects were better matched than in BFCRS-O. DIF analysis showed that certain items of both versions of BFCRS were influenced by the presence of negative symptoms. CONCLUSION: BFCRS-R is shorter and simpler than the original version and having better psychometric properties seems to be better suited for identifying and quantifying catatonia in chronic psychotic patients. PMID- 17849435 TI - Effectiveness of a home exercise programme in low back pain: a randomized five year follow-up study. AB - BACKGROUND AND PURPOSE: Therapeutic exercise has been shown to be beneficial in decreasing pain and in increasing functioning in patients with chronic low back pain. However, longitudinal follow-up studies are small in number, and often limited in the numbers of subjects due to drop-outs. In addition there is a shortage of real control groups in most cases. The purpose of the present study was to describe long-term changes in intensity of low back pain and in functioning for two study groups five years after undertaking a home exercise programme. METHOD: This was a randomized follow-up study over five years. Fifty seven subjects were reassessed with questionnaires five years after their initial recruitment for an intervention study. A home exercise group (n = 29), with training once a day, and a control group (n = 28), without exercise, were included in the present study protocol. The primary outcome measurements included a questionnaire on the intensity of low back pain (Borg CR-10 scale) and on functioning (Oswestry Disability Index; ODI). The confounding physical activity was controlled with metabolic unit (MET) values. RESULTS: The CR-10 and ODI scores decreased during the first three months in both study groups. During the follow-ups, the corresponding indicators of the home exercise group remained below baseline values. The CR-10 score was significantly lower in the home exercise group (p = 0.01) during the last five-year follow-up session compared with the control group. Overall physical activity decreased slightly during the five-year follow-up, but there were no differences between the two study groups. CONCLUSIONS: The present randomized study indicates that supervised, controlled home exercises lead to reduced low back pain, and that positive effects were preserved over five years. PMID- 17849436 TI - Rbp-j regulates expansion of pancreatic epithelial cells and their differentiation into exocrine cells during mouse development. AB - Notch signaling regulates cell fate determination in various tissues. We have reported the generation of mice with a pancreas-specific knockout of Rbp-j using Pdx.cre mice. Those mice exhibited premature endocrine and ductal differentiation. We now generated mice in which the Rbp-j gene was inactivated in Ptf1a-expressing cells using Ptf1a.cre mice. The timing of the Cre-mediated deletion in Rbp-j(f/f) Ptf1a.cre mice is 1 day later than that in Rbp-j(f/f) Pdx.cre mice. In Rbp-j(f/f) Ptf1a.cre mouse pancreases, at E13.5, the reduced Hes1 expression was accompanied by reduced epithelial growth, but premature endocrine cell differentiation was minimal. At E15.5, Pdx1 expression was repressed and acinar cell differentiation was reduced, but an increase in acinar cell proliferation was observed during the perinatal period. Our study indicates that, in addition to its role in preventing premature differentiation of early endocrine cells, Rbp-j regulates epithelial growth, Pdx1 expression, and acinar cell differentiation during mid-pancreatic development. PMID- 17849437 TI - Convergence and extension movements affect dynamic notochord-somite interactions essential for zebrafish slow muscle morphogenesis. AB - During vertebrate gastrulation, convergence and extension (C&E) movements shape and position the somites that form the fast and slow muscles. In zebrafish knypek;trilobite non-canonical Wnt mutants, defective C&E movements cause misshapen somites and reduction of slow muscle precursors, the adaxial cells. Here, we demonstrate essential roles of C&E in slow muscle morphogenesis. During segmentation, the adaxial cells change shapes and migrate laterally to form slow muscles at the myotome surface. Using confocal imaging techniques, we show that the adaxial cells undergo three-step shape changes, including dorsoventral elongation, anterior-ward rotation, and anteroposterior elongation. The adaxial cells in knypek;trilobite double mutants maintain prolonged contact with the notochord and fail to rotate anteriorly. Such a defect was suppressed by physical removal of their notochord or by introducing wild-type notochord cells into the mutant. We propose that in the double mutants, impaired C&E movements disrupt notochord development, which impedes the adaxial cell shape changes. PMID- 17849438 TI - Cdc42 is crucial for the establishment of epithelial polarity during early mammalian development. AB - To study the role of Cdc42 in the establishment of epithelial polarity during mammalian development, we generated murine Cdc42-null embryonic stem cells and analyzed peri-implantation development using embryoid bodies (EBs). Mutant EBs developed endoderm and underlying basement membrane, but exhibited defects of cell polarity, cell-cell junctions, survival, and cavitation. These defects corresponded to a decreased phosphorylation and membrane localization of aPKC, a reduced phosphorylation of GSK3beta, and a diminished activity of Rac1. However, neither Rac1 nor the kinase function of GSK3beta seem to contribute to cell polarization and cell-cell contacts. In contrast, EBs expressing dominant negative (dn) PKCzeta mimicked well the phenotype of Cdc42-null EBs, suggesting a major role of aPKC in mediating cell polarization downstream of Cdc42. Finally, aggregation experiments with endodermal cell lines suggested that Cdc42 might affect formation of adherens and tight junctions by PKCzeta-dependent regulation of the protein levels of p120 catenin and E-cadherin. PMID- 17849439 TI - Endoplasmic reticulum stress induced by tunicamycin disables germ layer formation in Xenopus laevis embryos. AB - Maintenance of endoplasmic reticulum (ER) homeostasis is essential for correct protein targeting and secretion. ER stress caused by accumulation of unfolded or misfolded proteins leads to disruption of cellular functions. We have investigated the effect of ER stress on Xenopus embryogenesis. ER stress induced by tunicamycin (TM) treatment of embryos resulted in defects affecting germ layer formation. We observed up-regulation of ER stress response genes, enhanced cytoplasmic splicing of xXBP1 RNA, and increased rate of apoptosis. In animal cap assays, TM treatment inhibited mesoderm formation induced by overexpression of activin/nodal RNA but did not affect mesoderm formation induced by functional activin protein, suggesting that dysfunction of ER caused a failure in activin/nodal processing and/or secretion. The observation that activin protein renders mesoderm formation under ER stress strengthens the role of activin/nodal for mesoderm induction. The results underline the functional significance of ER homeostasis in germ layer formation during Xenopus embryogenesis. PMID- 17849440 TI - Genetic interactions between activin type IIB receptor and Smad2 genes in asymmetrical patterning of the thoracic organs and the development of pancreas islets. AB - Signaling through activin type IIB receptor (ActRIIB) has been shown to regulate the axial formation and the development of foregut-derived organs such as the pancreas in mice. Here, we provide genetic evidence that ActRIIB and Smad2 genes cooperatively regulated asymmetrical patterning of the thoracic organs and pancreas development in mice. The loss of one allele of Smad2 on ActRIIB-/- background resulted in the increased severity of ActRIIB-/- phenotypes, including right pulmonary isomerism and complex cardiac malformations, and resulted in 100% frequency of death soon after birth. Of interest, 14% of compound heterozygous ActRIIB+/- Smad2+/- mice exhibited the ActRIIB-/- phenotypes and died soon after birth. In the pancreas, hypoplastic islets were found not only in ActRIIB-/- but also in Smad2+/- mice. A more severe phenotype was also found in ActRIIB+/- Smad2+/- mice. As well, these mutant mice exhibited impaired glucose tolerance in a gene dosage-sensitive manner. This genetic evidence strongly suggested that ActRIIB and Smad2 function in the same signaling pathway to regulate axial patterning and pancreas islet formation by means of a threshold mechanism. PMID- 17849441 TI - Dll3 and Notch1 genetic interactions model axial segmental and craniofacial malformations of human birth defects. AB - Mutations in the Notch1 receptor and delta-like 3 (Dll3) ligand cause global disruptions in axial segmental patterning. Genetic interactions between members of the notch pathway have previously been shown to cause patterning defects not observed in single gene disruptions. We examined Dll3-Notch1 compound mouse mutants to screen for potential gene interactions. While mice heterozygous at either locus appeared normal, 30% of Dll3-Notch1 double heterozygous animals exhibited localized, segmental anomalies similar to human congenital vertebral defects. Unexpectedly, double heterozygous mice also displayed statistically significant reduction of mandibular height and decreased length of the [corrected] maxillary hard palate. Examination of somite-stage embryos and perinatal anatomy and histology did not reveal any organ defects, so we used microarray-based analysis of Dll3 and Notch1 mutant embryos to identify gene targets that may be involved in notch-regulated segmental or craniofacial development. Thus, Dll3-Notch1 double heterozygous mice model human congenital scoliosis and craniofacial disorders. PMID- 17849442 TI - Fish fingers: digit homologues in sarcopterygian fish fins. AB - A defining feature of tetrapod evolutionary origins is the transition from fish fins to tetrapod limbs. A major change during this transition is the appearance of the autopod (hands, feet), which comprises two distinct regions, the wrist/ankle and the digits. When the autopod first appeared in Late Devonian fossil tetrapods, it was incomplete: digits evolved before the full complement of wrist/ankle bones. Early tetrapod wrists/ankles, including those with a full complement of bones, also show a sharp pattern discontinuity between proximal elements and distal elements. This suggests the presence of a discontinuity in the proximal-distal sequence of development. Such a discontinuity occurs in living urodeles, where digits form before completion of the wrist/ankle, implying developmental independence of the digits from wrist/ankle elements. We have observed comparable independent development of pectoral fin radials in the lungfish Neoceratodus (Osteichthyes: Sarcopterygii), relative to homologues of the tetrapod limb and proximal wrist elements in the main fin axis. Moreover, in the Neoceratodus fin, expression of Hoxd13 closely matches late expression patterns observed in the tetrapod autopod. This evidence suggests that Neoceratodus fin radials and tetrapod digits may be patterned by shared mechanisms distinct from those patterning the proximal fin/limb elements, and in that sense are homologous. The presence of independently developing radials in the distal part of the pectoral (and pelvic) fin may be a general feature of the Sarcopterygii. PMID- 17849443 TI - Reciprocal regulation of Notch and PI3K/Akt signalling in T-ALL cells in vitro. AB - Notch signalling plays an important role in hematopoiesis and in the pathogenesis of T-ALL. Notch is known to interact with Ras and PTEN/PI3K (phosphoinositide-3 kinase)/Akt pathways. We investigated the interaction of Notch with these pathways and the possible reciprocal regulation of these signalling systems in T ALL cells in vitro. Our analyses indicate that the PI3K/Akt pathway is constitutively active in the four T-ALL cell lines tested. Akt phosphorylation was not altered by the sequestration of growth factors, that is, Akt activation seems to be less dependent on but not completely independent of growth factors, possibly being not subject to negative feedback regulation. PTEN expression was not detected in 3/4 cell lines tested, suggesting the loss of PTEN-mediated Akt activation. Inhibition of the PI3K/Akt pathway arrests growth and enhances apoptosis, but with no modulation of expression of Bax-alpha and Bcl-2 proteins. We analysed the relationship between Notch-1 and the PI3K/Akt signalling and show that inhibition of the Akt pathway changes Notch expression; Notch-1 protein decreased in all the cell lines upon treatment with the inhibitor. Our studies strongly suggest that Notch signalling interacts with PI3K/Akt signalling and further that this occurs in the absence of PTEN expression. The consequences of this to the signalling outcome are yet unclear, but we have uncovered a significant inverse relationship between Notch and PI3K/Akt pathway, which leads us to postulate the operation of a reciprocal regulatory loop between Notch and Ras-PI3K/Akt in the pathogenesis of T-ALL. PMID- 17849444 TI - Synthesis, QSAR and calcium channel antagonist activity of new 1,4 dihydropyridine derivatives containing 1-methyl-4,5-dichloroimidazolyl substituents. AB - A group of dialkyl and diarylester analogues of nifedipine, in which the ortho nitrophenyl group at position 4 was replaced by a 1-methyl-4,5-dichloroimidazolyl substituent, were synthesized and evaluated as calcium-channel antagonists using the high K(+)concentration of guinea-pig ileum longitudinal smooth muscle. The structure of all compounds was confirmed by IR,(1)H-NMR, and mass spectra. The calcium-channel antagonist activity of compounds 10a-f demonstrated that compound 10b was the most active and 10f the least active one. With unsymmetrical diesters 12a-k, the most active compound was the ethyl, phenethyl derivative. Structural parameters on the calcium-channel antagonist activity were evaluated by QSAR analysis and a linear correlation was found between the -log IC(50) values of these compounds and their constitutional and topological properties. PMID- 17849445 TI - Synthesis and in-vitro activity of novel 1beta-methylcarbapenems having spiro[2,4]heptane moieties. AB - The synthesis of a new series of 1beta-methylcarbapenems having spiro[2,4]heptane moieties is described. Their in-vitro antibacterial activities against both gram positive and gram-negative bacteria were tested and the effect of substituents on the pyrrolidine ring was investigated. Most compounds were shown to be more active than the compared meropenem and imipenem against Escherichia coli. One particular compound, IIIb, having hydroxy a moiety showed the most potent antibacterial activity. PMID- 17849446 TI - SDX-308 and SDX-101, non-steroidal anti-inflammatory drugs, as therapeutic candidates for treating hematologic malignancies including myeloma. AB - Non-steroidal anti-inflammatory drugs have been shown to inhibit carcinogenesis in colon cancer, and to induce apoptosis in a variety of tumor cell lines. Some anti-tumor effects are thought to be related to their cyclooxygenase-2-inhibitory activity, but recent studies have shown that non-steroidal anti-inflammatory drugs exert their anti-tumor effect via cyclooxygenase-2-independent mechanism. SDX-308 (CEP-18082) is a non-cyclooxygenase-2-inhibiting indole-pyran analog and is structurally related to SDX-101, an R-enantiomer of etodolac. SDX-308 has a potent anti-myeloma effect and shows synergism in combination with other drugs for the treatment of chronic lymphocytic leukemia. In addition SDX-308 inhibits osteoclast formation and activity and thereby might be an attractive drug for the treatment of diseases with increased osteoclast activity such as osteolytic lesions in multiple myeloma and metastatic carcinomas, as well as osteoporosis. This review covers future application of SDX-308 as an anti-myeloma drug regulating increased osteoclast activity. PMID- 17849447 TI - Is your "gene of interest" interesting? AB - Has a large-scale screen turned up a potential gene-of-interest that you know nothing about? Your computer is a portal to a wealth of information that can save you valuable time and resources. Freely available data can help to determine whether a particular gene is worthy of further research, and what direction that research should take. Presented here are approaches to mining the Internet, including searching popular model organism databases. The primer covers two typical scenarios: the gene of interest is well characterized, or mostly uncharacterized. Also featured are interviews with Monte Westerfield, PhD, Director of the Zebrafish Information Network (ZFIN) online database, and Principal Investigator of the Human Protein Reference Database (HPRD) project, Akhilesh Pandey, MD, PhD. PMID- 17849448 TI - Short dysfunctional telomeres impair the repair of arsenite-induced oxidative damage in mouse cells. AB - Telomeres and telomerase appear to participate in the repair of broken DNA ends produced by oxidative damage. Arsenite is an environmental contaminant and a potent human carcinogen, which induces oxidative stress on cells via the generation of reactive oxygen species affecting cell viability and chromosome stability. It promotes telomere attrition and reduces cell survival by apoptosis. In this study, we used mouse embryonic fibroblasts (MEFs) from mice lacking telomerase RNA component (mTERC(-/-) mice) with long (early passage or EP) and short (late passage or LP) telomeres to investigate the extent of oxidative damage by comparing the differences in DNA damage, chromosome instability, and cell survival at 24 and 48 h of exposure to sodium arsenite (As3+; NaAsO2). There was significantly high level of DNA damage in mTERC(-/-) cells with short telomeres as determined by alkaline comet assay. Consistent with elevated DNA damage, increased micronuclei (MN) induction reflecting gross genomic instability was also observed. Fluorescence in situ hybridization (FISH) analysis revealed that increasing doses of arsenite augmented the chromosome aberrations, which contributes to genomic instability leading to possibly apoptotic cell death and cell cycle arrest. Microarray analysis has revealed that As3+ treatment altered the expression of 456 genes of which 20% of them have known functions in cell cycle and DNA damage signaling and response, cell growth, and/or maintenance. Results from our studies imply that short dysfunctional telomeres impair the repair of oxidative damage caused by arsenite. The results will have implications in risk estimation as well as cancer chemotherapy. PMID- 17849449 TI - Understanding ion channel biology using epitope tags: progress, pitfalls, and promise. AB - Epitope tags have been increasingly used to understand ion channel subunit assembly and interaction, trafficking, subcellular localization, and function in living cells. In particular, epitope tags have proven extremely useful for analyses of closely related, highly homologous channel subunits in endogenous cell contexts in vitro and in vivo, where multiple channel isoforms may be expressed. However, as the variety of epitope tags that have been used has expanded, and the use of tagged channel subunits has become increasingly sophisticated and widespread, there has also been an increase in the number of examples highlighting the potential problems associated with the use of epitope tags for ion channel studies. Described here are some of the epitope tags that have been used to study ion channel subunits, including the HA, FLAG, myc, His6, and green fluorescent protein (GFP) epitopes, as well as some of the applications and avenues of research in which they have proven advantageous. Potential pitfalls and caveats associated with the use of these epitope tags are also discussed, with an emphasis on the need to include careful characterization of epitope-tagged channel subunits as part of their construction. Finally, potential avenues for future investigation and the development of this approach are considered. PMID- 17849451 TI - TAE226-induced apoptosis in breast cancer cells with overexpressed Src or EGFR. AB - Focal adhesion kinase, FAK is a 125 kDa nonreceptor tyrosine kinase that localizes to focal adhesions. FAK is overexpressed in human tumors and regulates cellular adhesion and survival signaling. We have shown previously that the dominant-negative FAK, C-terminal FAK-CD, caused detachment and apoptosis in human breast cancer cells, and that overexpression of an activated form of Src tyrosine kinase or epidermal growth factor receptor, EGFR, suppressed FAK-CD induced apoptotic effects in breast cancer cells. In the present study, we studied the effect of a novel FAK inhibitor, TAE226 (Novartis, Inc.), on the breast cancer cell lines. We used stable breast cancer cell lines overexpressing Src (MCF-7-Src and BT474-Src) or overexpressing EGFR (BT474-EGFR), and control breast cancer cell lines for the treatment with different doses of TAE226 drug. The detachment and apoptosis caused by TAE226 was analyzed and compared with the effect of the dominant-negative adenoviral FAK-CD. The TAE226 drug caused a dose dependent increase of detachment and apoptosis in both BT474 and MCF-7-Vector and Src cells and in BT474-EGFR and BT474-pcDNA3 cells. Additionally, TAE226 caused downregulation of Y397-FAK, FAK and activation of PARP or caspase-3 proteins. Both Src and EGFR-overexpressing cells were not resistant to the TAE226 treatment compared to FAK-CD treatment. In addition, normal breast MCF-10A cell line was resistant to both TAE226 drug and to the Ad-FAK-CD inhibitor. Thus, inhibition of autophosphorylation activity of FAK with the TAE226 inhibitor at 10-20 microM is effective in causing apoptosis in breast cancer cells, resistant to the Ad-FAK-CD inhibitor that can be used effectively in therapy. PMID- 17849452 TI - Modulation by bexarotene of mRNA expression of genes in mouse lung tumors. AB - Bexarotene has demonstrated chemopreventive and therapeutic efficacy towards mouse lung tumors. Using specimens from our published study that demonstrated the efficacy of bexarotene, we report herein its ability to modulate mRNA expression of genes in both lung and lung tumors. Strain A/J mice were administered vinyl carbamate to induce lung tumors. This was followed by 200 mg/kg body weight of bexarotene administered by oral gavage during Wks 4-25 or 23-25. The mice were sacrificed at Wk 25. The expression of 26 genes was decreased in lung tumors, whereas only two genes, Apolipoprotein D and CYP26b, had their mRNA expression increased by bexarotene. Genes with increased mRNA expression in untreated lung tumors include: epiregulin and kininogen-1 (increased by more than 40-fold) and Caspase-3, Cyclin D1, DNA methyltransferase 3a (Dnmt-3a), E-prostanoid 3 receptor (EP3), c-myc, surfactant protein-C, and survivin (increased by 1.7- to 3.6-fold). Bexarotene decreased the mRNA expression of Caspase-3, Dnmt-3a, EP3, and survivin, as well as the expression of the Cyclin E1, estrogen receptor-alpha, and iNOS genes. Bexarotene had a greater effect in decreasing the expression of Caspase-3, Cyclin E1, Dnmt-3a, EP3, iNOS, and survivin, when administered to mice with established tumors than when administered to mice while tumors were emerging. In summary, bexarotene modulated mRNA expression of genes in mouse lung tumors, being more effective in established tumors than in emerging tumors, suggesting that modulation of expression could be useful as a biomarker for the therapeutic and chemopreventive activity of the drug, especially in established tumors. PMID- 17849453 TI - Experimental induction of palate shelf elevation in glutamate decarboxylase 67 deficient mice with cleft palate due to vertically oriented palatal shelf. AB - BACKGROUND: Gamma-aminobutyric acid is an inhibitory neurotransmitter, synthesized by two isoforms of glutamate decarboxylase (GAD), GAD65 and -67. Unexpectedly, inactivation of GAD67 induces cleft palate in mice. Reduction of spontaneous tongue movement resulting from decreased motor nerve activity has been related to the development of cleft palate in GAD67(-/-) fetuses. In the present study, development of cleft palate was examined histologically and manipulated with culture of the maxilla and partial resection of fetal tongue. METHODS: GAD67(-/-) mice and their littermates were used. Histological examination and immunohistochemistry were performed conventionally. Organ culture of the maxilla was carried out as reported previously. Fetuses were maintained alive under anesthesia and tips of their tongues were resected. RESULTS: Elevation of palatal shelves, the second step of palate formation, was not observed in GAD67(-/-) mice. In wild-type mice, GAD67 and gamma-aminobutyric acid were not expressed in the palatal shelves, except in the medial edge epithelium. During 2 days of culture of maxillae dissected from E13.5-E14.0 GAD67(-/-) fetuses, elevation and fusion of the palatal shelves were induced. When E13.5 15.5 mutant fetuses underwent partial tongue resection, the palatal shelves became elevated within 30 min. CONCLUSIONS: These results suggest that the potential for palate formation is maintained in the palatal shelves of GAD67(-/-) fetuses, but it is obstructed by other, probably neural, factors, resulting in cleft palate. PMID- 17849454 TI - Neuroprotection in the SAINT-II aftermath. PMID- 17849455 TI - Dynamic expression of thyrotropin-releasing hormone in the mouse definitive endoderm. AB - Thyrotropin-releasing hormone (TRH) is a well-characterized regulator of the hypothalamic-pituitary-thyroid endocrine axis. Here, we describe the expression of Trh during early embryonic development in the mouse. We find Trh to be highly expressed during postimplantation stages in the mouse embryo, with expression first observed in the epiblast at embryonic day (E) 6.5. During gastrulation, Trh is expressed in the newly formed definitive endoderm cells, and at embryonic day (E) 7.75, marks the entire definitive endoderm. Subsequently, Trh mRNA levels rapidly decrease such that, by E9.0, expression in the definitive endoderm is no longer detected, after which neural expression predominates. Thus, Trh is expressed dynamically and specifically in the developing mouse definitive endoderm from E7.0 to E8.5. Trh is unique among definitive endoderm markers as it transiently marks the entire definitive endoderm population and is not expressed in the extraembryonic endoderm. Trh will be a valuable tool to study definitive endoderm formation in the mouse embryo. PMID- 17849456 TI - Imaging the migrating border cell cluster in living Drosophila egg chambers. AB - Cell migration is a key process in animal development and central to the spread of cancer. Border cell migration in Drosophila egg chambers is an excellent general model for cell migration, but lacks techniques for studying this process in living cells. Here, we describe a simple and effective method of preparing egg chambers in halocarbon oil. The movement and behavior of the migrating border cells can reproducibly be followed in up to 25 egg chambers simultaneously by time-lapse microscopy using a variety of green fluorescent protein markers on a widefield microscope over a period of 4 hr. Our studies reveal a remarkably linear migration route of the border cell cluster and highly dynamic activity within their cluster. Migrating cells rapidly alter their relative positions and generate transient protrusions. These activities are likely to play key roles in the mechanism of migration and cannot readily be analyzed using fixed samples. PMID- 17849457 TI - Serial cloning of pigs by somatic cell nuclear transfer: restoration of phenotypic normality during serial cloning. AB - Somatic cell nuclear transfer (scNT) is a useful way to create cloned animals. However, scNT clones exhibit high levels of phenotypic instability. This instability may be due to epigenetic reprogramming and/or genomic damage in the donor cells. To test this, we produced transgenic pig fibroblasts harboring the truncated human thrombopoietin (hTPO) gene and used them as donor cells in scNT to produce first-generation (G1) cloned piglets. In this study, 2,818 scNT embryos were transferred to 11 recipients and five G1 piglets were obtained. Among them, a clone had a dimorphic facial appearance with severe hypertelorism and a broad prominent nasal bridge. The other clones looked normal. Second generation (G2) scNT piglets were then produced using ear cells from a G1 piglet that had an abnormal nose phenotype. We reasoned that, if the phenotypic abnormality of the G1 clone was not present in the G2 and third-generation (G3) clones, or was absent in the G2 clones but reappeared in the G3 clones, the phenotypic instability of the G1 clone could be attributed to faulty epigenetic reprogramming rather than to inherent/accidental genomic damage to the donor cells. Blastocyst rates, cell numbers in blastocyst, pregnancy rates, term placenta weight and ponderal index, and birth weight between G1 and G2 clones did not differ, but were significantly (P < 0.05) lower than control age- and sex matched piglets. Next, we analyzed global methylation changes during development of the preimplantation embryos reconstructed by donor cells used for the production of G1 and G2 clones and could not find any significant differences in the methylation patterns between G1 and G2 clones. Indeed, we failed to detect the phenotypic abnormality in the G2 and G3 clones. Thus, the phenotypic abnormality of the G1 clone is likely to be due to epigenetic dysregulation. Additional observations then suggested that expression of the hTPO gene in the transgenic clones did not appear to be the cause of the phenotypic abnormality in the G1 clones and that the abnormality was acquired by only a few of the G1 clone's cells during its gestational development. PMID- 17849458 TI - Expression of the murine retinol dehydrogenase 10 (Rdh10) gene correlates with many sites of retinoid signalling during embryogenesis and organ differentiation. AB - Retinoic acid acts as a signalling molecule regulating many developmental events in vertebrates. As this molecule directly influences gene expression by activating nuclear receptors, its patterns of synthesis have to be tightly regulated, and it is well established that at least three retinaldehyde dehydrogenases (RALDHs) are involved in such tissue-specific synthesis. Whereas embryos from oviparous species can obtain retinaldehyde by metabolizing carotenoids stored in the yolk, placental embryos rely on retinol transferred from the maternal circulation. Here, we show that the gene encoding one of the murine retinol dehydrogenases, Rdh10, is expressed according to complex profiles both during early embryogenesis and organ differentiation. Many of its expression sites correlate with regions of active retinoid signalling and Raldh gene expression, especially with Raldh2 in the early presomitic and somitic mesoderm, retrocardiac and posterior branchial arch region, or later in the pleural mesothelium and kidney cortical region. Rdh10 also shows cell-type and/or regional specificity during development of the palate, teeth, and olfactory system. During limb bud development, it may participate in retinoic acid production in proximal/posterior cells, and eventually in interdigital mesenchyme. These data implicate the retinol to retinaldehyde conversion as the first step in the tissue-specific regulation of retinoic acid synthesis, at least in mammalian embryos. PMID- 17849459 TI - Marijuana coping motives interact with marijuana use frequency to predict anxious arousal, panic related catastrophic thinking, and worry among current marijuana users. AB - The present investigation evaluated whether coping motives for marijuana use interacted with past 30-day frequency of marijuana use in relation to anxiety relevant variables among community-recruited young adult marijuana users (n=149). As expected, after covarying cigarettes per day, alcohol use, and total years of marijuana use, the interaction between frequency of past 30-day marijuana use and coping motives predicted anxious arousal symptoms, agoraphobic cognitions, and worry. Marijuana users who demonstrated high use frequency and high coping motives demonstrated the highest levels of anxiety across these anxiety-relevant criterion variables. No such effects were evident, as expected, for depressive symptoms, offering explanatory specificity for anxiety relative to depressive factors. These results are discussed in relation to better understanding the role of marijuana use and coping motives in regard to anxiety vulnerability. PMID- 17849460 TI - PEG-IFN-alpha-2b therapy in BCR-ABL-negative myeloproliferative disorders: final result of a phase 2 study. AB - BACKGROUND: Interferon-alpha (IFN-alpha) has shown significant activity in the treatment of BCR-ABL-negative myeloproliferative disorders (MPDs), particularly essential thrombocythemia (ET) and polycythemia vera (PV). PEG-IFN-alpha-2b is a pegylated IFN-alpha-2b with a significant advantage over nonpegylated form in that it is administered once a week. METHODS: Thirty-eight patients with BCR-ABL negative MPDs were treated with PEG-IFN-alpha-2b, given subcutaneously weekly, at the starting dose of 3 microg/kg/wk for the first 14 patients and then 2 microg/kg/wk for the next 24 patients, with intent to treat patients as long as they benefited from the therapy. RESULTS: Median age was 54 years. Patient diagnoses were: 13 (34%) ET; 11 (29%) primary myelofibrosis (PMF); 5 (13%) BCR ABL-negative chronic myeloid leukemia (CML); 4 (10.5%) hypereosinophilic syndrome (HES); 4 (10.5%) PV; and 1 (3%) unclassified myeloproliferative disease (uMPD). Recorded grade 3-4 toxicities were related to fatigue, myelosuppression, and musculoskeletal pain. Ten (26%) patients stopped treatment because of toxicity. Thirteen (34%) patients achieved a complete remission, and 4 (11%) achieved a partial response. Only 1 patient with PMF responded. Median time to response was 5 months. Median duration of response was 20 months. Three patients had a sustained response for >24 months. CONCLUSIONS: PEG-IFN-alpha-2b, with proper dose modifications, is effective in controlling disease in a significant proportion of BCR-ABL-negative MPD patients, particularly ET and PV. However, toxicities encountered with PEG-IFN-alpha-2b therapy are similar to those obtained with conventional IFN-alpha, thus limiting the duration of therapy. PMID- 17849461 TI - Loss of programmed cell death 4 expression marks adenoma-carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer. AB - BACKGROUND: Programmed cell death 4 (Pdcd4) inhibits malignant transformation, and initial studies of Pdcd4 suggested the regulation of Pdcd4 localization by protein kinase B (Akt). However, supporting patient tissue data are missing, and the diagnostic/prognostic potential of Pdcd4 rarely has been studied. The objectives of the current were 1) to determine Pdcd4 as a diagnostic marker in the adenoma-carcinoma sequence, 2) to support phosphorylated Akt (pAkt)-mediated Pdcd4 regulation in vivo, and 3) to obtain the first prognostic evidence of Pdcd4 in colorectal cancer. METHODS: Tumor samples and normal tissues from 71 patients with colorectal cancer who were followed prospectively (median follow-up, 36 months) and 42 adenomas were analyzed for Pdcd4, Akt, and pAkt in immunohistochemical and Western blot analyses. RESULTS: A significant reduction in Pdcd4 was observed between normal mucosa and adenomas and between adenomas and tumor samples (P < .01 and P < .01, respectively). Normal mucosa demonstrated strong nuclear Pdcd4, which was reduced significantly in adenomas (P < .01) and almost was lost in tumors (P < .01). pAkt was correlated inversely with Pdcd4 and with the transition of Pdcd4 from nucleus to cytoplasm (P < .01). Kaplan-Meier analysis (using the Mantel-Cox log-rank test) indicated a significant correlation between the loss of total and nuclear Pdcd4 in tumors and overall survival (P < .05 and P < .02, respectively) and disease-specific survival (P < .01 and P < .01, respectively). In multivariate analysis, loss of total or nuclear Pdcd4 was an independent predictor of disease-specific or overall survival. CONCLUSIONS: To the authors' knowledge, this is the first study to demonstrate an independent prognostic impact of Pdcd4 and its expression pattern in colorectal cancer. Data from this study support the regulation of Pdcd4 localization by pAkt in vivo. Pdcd4 immunohistochemistry may be useful as a supportive diagnostic tool for the transition between normal, adenoma, and tumor tissues. PMID- 17849462 TI - Reproductive history, infertility treatment, and the risk of acute leukemia in children with down syndrome: a report from the Children's Oncology Group. AB - BACKGROUND: Children with Down syndrome (DS) have from 10 to 20 times the risk of developing acute leukemia than the general pediatric population. There is mixed evidence for associations between reproductive history or infertility and acute leukemia among children without DS. METHODS: The authors conducted a case-control study of acute leukemia among children with DS to investigate possible risk factors in this population. From 1997 to 2002, 158 children aged <20 years with DS who had a diagnosis of acute leukemia (97 children with acute lymphoblastic leukemia [ALL] and 61 children with acute myeloid leukemia [AML]) were enrolled at Children's Oncology Group (COG) institutions. Controls with DS (n = 173) were selected from the cases' primary care clinic and frequency matched to cases on age. Telephone interviews were conducted with mothers of cases and controls assessing reproductive history, infertility, and infertility treatment. RESULTS: Null results were observed overall and by subtype for reproductive factors, including previous pregnancy outcomes and contraceptive use, and for most infertility outcomes. There was an increased risk of AML among children with DS whose parents had ever tried for >/=1 year to become pregnant (odds ratio [OR], 2.22; 95% confidence interval [95% CI], 1.14-4.33). A 1-year increase in maternal age also was associated with AML (OR, 1.06; 95% CI, 1.01-1.12). CONCLUSIONS: Although the questionnaire was limited in this area, the results suggested that the risk for AML may be raised in children with DS because of infertility. In that the risk of infertility, along with having a child with DS, increase with age, these results warrant more research. PMID- 17849463 TI - Zone-specific remodeling of tumor blood vessels affects tumor growth. AB - BACKGROUND: Chaotic organization, abnormal leakiness, and structural instability are characteristics of tumor vessels. However, morphologic events of vascular remodeling in relation to tumor growth are not sufficiently studied yet. METHODS: By using the rat rhabdomyosarcoma tumor model vascular morphogenesis was studied by light and electron microscopy and immunohistochemistry in relation to tumor regions such as tumor surrounding (TSZ), marginal (TMZ), intermediate (TIZ), and center (TCZ) zones. RESULTS: The analyses revealed that blood vessels of TSZ display a regular ultrastructure, whereas blood vessels of TMZ showed a chaotic organization and unstable structure with a diffuse or even lacking basal lamina, and missing or irregular assembled periendothelial cells. In contrast, blood vessels of TIZ and TCZ exhibited a more or less stabilized vessel structure with increased diameter. Correspondingly, normal assembly of alpha-smooth-muscle-actin (alpha-SMA)-positive cells into the vessel wall was observed in blood vessels of TSZ, TIZ, and TCZ. Also, Ang1 immunostaining was strongest in large vessels of TIZ and TCZ, whereas Ang2 staining was prominent in small vessels of TIZ. Tie2 staining was detectable in small and large vessels of all tumor zones. Immunostaining for alpha(v)beta(3)-integrin was strongest in small vessels of TMZ, whereas large vessels of TIZ and TCZ were almost negative. CONCLUSIONS: The results indicate a zone-specific remodeling of tumor blood vessels by stabilization of vessels in TIZ and TCZ, whereas small vessels of these zones obviously undergo regression leading to tumor necrosis. Thus, a better understanding of vascular remodeling and stabilization in tumors would enable new strategies in tumor therapy and imaging. PMID- 17849464 TI - Successful treatment with rituximab in a patient with an acquired factor V inhibitor. AB - Rituximab has already been successfully used to treat immune-mediated bleeding disorders such as acquired factor VIII inhibitor. We report here a case of severe acquired factor V (FV) inhibitor deficiency due to FV inhibitor which has been dramatically improved after rituximab. PMID- 17849465 TI - Successful treatment of cytomegalovirus-associated hemophagocytic syndrome by intravenous immunoglobulins. AB - Virus-associated hemophagocytic syndrome (VAHS) is a rare complication in early cytomegalovirus (CMV) infection. There is no standard therapy for VAHS and the clinical course is variable. Data on the use of intravenous immunoglobulin (IVIG) in the treatment of CMV-associated VAHS are limited. We report a previously healthy, 32-year-old woman who presented with general malaise, fever, chills, and splenomegaly. Laboratory examination showed marked elevation of aminotransferase, leucopoenia, and thrombocytopenia. Acute CMV-infection was documented by the presence of immunoglobulin M anti-CMV and positive viremia in blood sample. Bone marrow examination revealed extensive hemophagocytosis. IVIG was administered after the diagnosis of CMV-associated VAHS. Her symptoms and laboratory abnormalities improved dramatically after the onset of the treatment and she did not require antiviral agent. PMID- 17849466 TI - Surviving colorectal cancer : patient-reported symptoms 4 years after diagnosis. AB - BACKGROUND: The number of long-term survivors after a cancer diagnosis is increasing, yet relatively few studies have addressed survivors' reported symptoms beyond the initial year after diagnosis. METHODS: The symptom reports of 474 survivors of colon and rectal cancer from 5 US metropolitan areas were collected during 2002-2003 as part a larger study of the quality of care for patients with cancer diagnosed in 1998. The relation between the prevalence of reported symptoms and prior treatments received was analyzed, adjusting statistically for other patient characteristics. RESULTS: Sixty-nine percent of the survivors had colon cancer and 31% had rectal cancer. The most commonly reported symptoms were "fatigue" (23%), "negative feelings about body appearance" (14%), "diarrhea" (13%), and "constipation" (7%). Higher percentages of respondents attributed health effects to cancer or its treatment including "worry about health" (24%), "physical discomfort" (19%), and "activity limitations" (15%). In general, prior treatment was not associated with symptom prevalence. However, radiation therapy recipients and patients that received a diverting ostomy were more likely than others to report some of the symptoms we studied. Attribution of health effects to disease or treatment did not vary by prior treatment except that recipients of radiation therapy were more likely than others to report limitations in their activities (30% vs 10%; P = .003). CONCLUSIONS: Among colorectal cancer survivors the prevalence of symptoms at 4 years was low and relatively comparable to published estimates for the general population, but some survivors continue to attribute health effects to cancer or its treatment. PMID- 17849467 TI - Biologic significance of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) as a pivotal regulator of tumor growth through angiogenesis in human uterine cancer. AB - BACKGROUND: The expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is related significantly to the overall survival of patients with various cancers. RCAS1 reportedly induces apoptotic cell death in peripheral lymphocytes, which may contribute to the escape of tumor cells from immune surveillance. RCAS1 expression also has been related to tumor invasiveness and size in uterine cervical cancer. To clarify whether RCAS1 exacerbates tumor progression, the authors investigated the association between RCAS1 expression and tumor growth potential. METHODS: The authors constructed small interfering ribonucleic acid (RNA) (siRNA) to target RCAS1. After transfection of siRNA and the RCAS1-encoding gene, growth of tumor cells was assessed in vitro and in vivo. The correlation between RCAS1 expression and angiogenesis was investigated in the transfected cells and in inoculated tumors from nude mice. In addition, the same association was investigated immunohistochemically with tissue samples from patients with uterine cervical cancer. RESULTS: Knockdown of RCAS1 expression by siRNA significantly suppressed the in vivo growth of SiSo and HOUA tumor cells (P < .005); however, in vitro cell growth was not affected significantly. Enhanced RCAS1 expression significantly promoted in vivo growth, but not in vitro growth, of tumors derived from COS-7 cells (P = .0039). Introduction of the RCAS1 encoding gene increased expression of vascular endothelial growth factor (VEGF). In uterine cervical cancer, RCAS1 expression was associated significantly with VEGF expression (P = .0407) and with microvessel density (P = .0108). CONCLUSIONS: RCAS1 may be a pivotal regulator of tumor growth through angiogenesis. Continued exploration of the biologic function of RCAS1 may allow the development of novel therapeutic strategies for uterine cancer. PMID- 17849468 TI - Descriptive nomograms of adjuvant radiotherapy use and patterns of care analysis for stage I and II endometrial adenocarcinoma: A surveillance, epidemiology, and end results population study. AB - BACKGROUND: Although endometrial cancer remains the most common gynecologic malignancy in the United States, differing approaches to adjuvant radiotherapy treatment for early disease exist within the medical community because of the lack of a national consensus. METHODS: The authors studied patterns of adjuvant care for stage I and II endometrial adenocarcinoma using a large United States population database. A retrospective analysis was conducted from the Surveillance, Epidemiology, and End Results (SEER) Program of the U.S. National Cancer Institute from 1988 to 2002, and 26,923 women with American Joint Committee on Cancer stage I and II endometrial adenocarcinoma were selected. The following prognostic factors were analyzed: age, race, stage, grade, year of diagnosis, SEER registry location, and use and type of postoperative radiotherapy (RT). Adjuvant RT was coded as none, external-beam RT (EBRT), brachytherapy (BR), or a combination of the 2 (EBRT + BR). RESULTS: Higher tumor grade and stage led to greater use of RT. The odds ratio (OR) for adjuvant RT was 3.4 for stage IB versus stage IA and 51.8 for stage IC/II versus stage IA. The effect of grade depended on stage: for stages IA and IB, the OR was 2.9 for grade 2 versus grade 1 and 11.7 for grade 3/4 versus grade 1; whereas, for stage IC/II, the OR was 1.5 for grade 2 versus grade 1 and 2.0 for grade 3/4 versus grade 1. Within stage I, increasing substage and grade increased the odds of EBRT with or without BR compared with BR alone. Race did not effect the choice of therapy (all P > .1). Geographic location had a significant effect on overall RT use and therapy choice. CONCLUSIONS: To the authors' knowledge, this was the largest patterns of care analysis to date of adjuvant RT in patients with stage I and II endometrial adenocarcinoma. The current study revealed that there is significant diversity in the use of adjuvant RT across the United States, and the results reflected the absence of a national consensus on adjuvant treatment for early-stage disease. PMID- 17849469 TI - Lack of P2X receptor mediated currents in astrocytes and GluR type glial cells of the hippocampal CA1 region. AB - Purinergic signalling plays a major role in intercellular communication between neurons and glial cells. Glial cells express metabotropic receptors for ATP and adenosine, the latter being activated after ATP cleavage through extracellular ecto-ATPase activity. Ionotropic receptors for extracellular ATP, so called P2X receptors, might contribute to neuron-glia signalling. However, experimental evidence for the presence of these receptors in glial cells is less convincing so far. In a previous study, immunohistochemistry was used to identify P2X(1-4,6,7) receptor protein in S100beta-positive hippocampal glial cells. Applying patch clamp and fast application techniques, here we challenged the question of the functional expression of these receptors. Time correlated membrane currents served as test criterion for receptor function, since P2X receptor activation leads to the opening of unspecific cation channels in a millisecond time scale. Agonists were applied via short pressure puffs, with a fast concentration clamp method and through UV flash triggered photolysis of caged ATP. Two types of murine hippocampal macroglial cells, both labelled by the expression of green fluorescence protein driven by the human glial fibrillary acid protein promoter, were analysed in acute brain slices and in freshly dissociated cell suspensions. Surprisingly, ATP or related agonists completely failed to activate currents. Additionally, changes in spontaneously occurring glial postsynaptic currents were never observed. These results have been verified using rat and human hippocampal tissue as well as investigating cells from P2X7 knock out mice. It is concluded that in acute preparations, astroglial cells of the hippocampal CA1 subfield do not express functional P2X receptors. PMID- 17849470 TI - Interleukin-6 and its receptor in cancer: implications for translational therapeutics. AB - Interleukin-6 (IL-6) plays a major role in the response to injury or infection and is involved in the immune response, inflammation, and hematopoiesis. Its deregulation impacts numerous disease states, including many types of cancer. Consequently, modulating IL-6 may be an innovative therapeutic strategy in several diseases. A review of relevant published literature regarding IL-6 and its receptor was performed. In addition, a review of the relevance of this cytokine system to human illness, particularly in cancer, was undertaken. IL-6 is a pleiotropic cytokine that is involved in the physiology of virtually every organ system. Aberrant expression of this cytokine has been implicated in diverse human illnesses, most notably inflammatory and autoimmune disorders, coronary artery and neurologic disease, gestational problems, and neoplasms. In cancer, high levels of circulating IL-6 are observed in almost every type of tumor studied and predict a poor outcome. Furthermore, elevated IL-6 levels are associated strongly with several of the striking phenotypic features of cancer. Several molecules have been developed recently that target the biologic function of IL-6. Early results in the clinic suggest that this strategy may have a significant salutary impact on diverse tumors. The field of cytokine research has yielded a deep understanding of the fundamental role of IL-6 and its receptor in health and disease. Therapeutic targeting of IL-6 and its receptor in cancer has strong biologic rationale, and there is preliminary evidence suggesting that targeting of the IL-6 system may be beneficial in the treatment of cancer. PMID- 17849471 TI - Serum and forskolin cooperate to promote G1 progression in Schwann cells by differentially regulating cyclin D1, cyclin E1, and p27Kip expression. AB - Proliferation of Schwann cells in vitro, unlike most mammalian cells, is not induced by serum alone but additionally requires cAMP elevation and mitogenic stimulation. How these agents cooperate to promote progression through the G1 phase of the cell cycle is unclear. We studied the integrative effects of these compounds on receptor-mediated signaling pathways and regulators of G1 progression. We show that serum alone induces strong cyclical expression of cyclin D1 and E1, 6 and 12 h after addition, respectively. Serum also promotes strong but transient erbB2, ERK, and Akt phosphorylation, but Schwann cells remain arrested in G1 due to high levels of the inhibitor, p27(Kip). Forskolin with serum promotes G1 progression in 22% of Schwann cells between 18 and 24 h by inducing a steady decline in p27(Kip) levels that reaches a nadir at 12 h coinciding with peak cyclin E1 expression. Forskolin also delays neuregulin induced loss of erbB2 receptors allowing strong acute activation of PI3K, sustained erbB2 phosphorylation and G1 progression in 31% of Schwann cells. We find that the ability of forskolin to decrease p27(Kip) is associated with its ability to decrease Krox-20 expression that is induced by serum and further increased by neuregulin. Our results explain why serum is required but insufficient to stimulate proliferation and identify two routes by which forskolin promotes proliferation in the presence of serum and neuregulin. These findings provide insights into how G1 progression and, cell cycle arrest leading to myelination are regulated in Schwann cells. PMID- 17849472 TI - Synergy of karenitecin and mafosfamide in pediatric leukemia, medulloblastoma, and neuroblastoma cell lines. AB - BACKGROUND: A major barrier to treatment of leptomeningeal disease is the lack of proven combination chemotherapy regimens for intrathecal administration. The purpose of this study was to determine the cytotoxic effects of karenitecin and mafosfamide in vitro against leukemia, medulloblastoma, and neuroblastoma cell lines. PROCEDURE: A modified methyl tetrazolium (MTT) assay was used to determine the sensitivity of the cells to karenitecin and mafosfamide. Cells were exposed to drug for 72 hr, after which the number of surviving cells was quantitated. For drug combination experiments, cells were exposed to medium alone (controls), single drugs alone (mafosfamide only, karenitecin only) or to different concentrations of the combination of the two drugs (karenitecin + mafosfamide), for a total of 36 concentration pairs per plate. The universal response surface approach (URSA) was used to analyze the cytotoxic effects of the combination of karenitecin and mafosfamide. RESULTS: The IC(50)s of karenitecin and mafosfamide for the various cell lines were similar. For both drugs nearly complete inhibition of cell growth was demonstrated at higher concentrations in all cell lines. In the neuroblastoma cell lines (SK-N-DZ; SK-N-SH) and the DAOY medulloblastoma cell line, the combination of karenitecin and mafosfamide were synergistic. In the D283 medulloblastoma and both the leukemia cell lines (JM1 and Molt-4), the drug interaction was additive. Antagonism was not seen in any cell line. CONCLUSIONS: Karenitecin and mafosfamide are additive or synergistic in vitro against tumor types that disseminate to the leptomeninges. These results provide guidance for the choice of potential combination intrathecal regimens. PMID- 17849473 TI - The British Childhood Cancer Survivor Study: Objectives, methods, population structure, response rates and initial descriptive information. AB - BACKGROUND: In Britain 75% of individuals diagnosed with childhood cancer survive at least 5 years. The British Childhood Cancer Survivor Study was established to determine the risks of adverse health and social outcomes among survivors. To be eligible individuals were diagnosed with childhood cancer in Britain between 1940 and 1991 and survived at least 5 years. The entire cohort of 17,981 form the basis of population-based studies of late mortality and the risks/causes of second malignant neoplasms using national registration systems. METHODS: A postal questionnaire was sent to survivors who were alive and aged at least 16 years via their primary care physician. RESULTS: Of the 14,836 survivors eligible to receive a questionnaire, 10,483 (71%) returned it completed. Of the 13,211 who were mailed a questionnaire by their primary care physician 10,483 (79%) returned it completed. Outline treatment information concerning initial radiotherapy, chemotherapy and surgery is available. CONCLUSIONS: This is the largest available population-based cohort of childhood cancer survivors to have included investigation of a wide spectrum of adverse outcomes (the risk of which might be increased as a result of childhood cancer or its treatment). The study should provide useful information for counselling survivors, planning long-term clinical follow-up and evaluating the long-term risks likely to be associated with proposed treatment strategies. PMID- 17849474 TI - Corticosteroids and increased risk of readmission after acute chest syndrome in children with sickle cell disease. AB - BACKGROUND: Acute chest syndrome (ACS) is a frequent cause of hospitalization and mortality in children with sickle cell disease. Transfusion is often required to prevent respiratory failure and treatment with dexamethasone may reduce the length of admission and the need for transfusions. We performed a retrospective cohort study to evaluate risk factors for readmission and prolonged hospitalization after different treatments for ACS. PROCEDURE: We identified patients <22 years of age hospitalized with ACS at Johns Hopkins Hospital from January 1998 to April 2004 using the hospitals discharge database and by reviewing dictated summaries. RESULTS: We identified 65 patients with 129 episodes of ACS (mean age 12.5 years, range 1.2-21.9 years). Thirty-nine episodes were treated with corticosteroids and 51 with transfusions. Patients were readmitted within 14 days after 23 episodes (18%). Readmission was strongly associated with report of an inhaler or nebulizer at home [odds ratio (OR) 6.0, P < 0.05], diastolic BP at 48 hr (OR 1.8 per 10 mm increase, P<0.01), corticosteroids (OR 20, P < 0.005), or transfusion (OR 0.03, P < 0.05). Treatment with corticosteroids alone (P < 0.05) and older age (P < 0.001) were associated with longer hospitalization. CONCLUSIONS: These results demonstrate a greatly elevated independent risk of readmission after ACS in children with asthma and after treatment with corticosteroids and a protective effect of transfusion. Although dexamethasone has documented efficacy for reducing the duration of ACS, the substantial risk of readmission for pain should limit its use. PMID- 17849475 TI - Altered expression of the urokinase receptor homologue, C4.4A, in invasive areas of human esophageal squamous cell carcinoma. AB - C4.4A is a glycolipid-anchored membrane protein with structural homology to the urokinase-type plasminogen activator receptor (uPAR). Although C4.4A was identified as a metastasis-associated protein little is known about its actual expression and possible function in malignant disease. In the present study, we have therefore analyzed the expression of C4.4A in 14 esophageal squamous cell carcinomas (ESCC). Normal squamous esophageal epithelium shows a strong cell surface associated C4.4A expression in the suprabasal layers, whereas basal cells are negative. Upon transition to dysplasia and carcinoma in situ the expression of C4.4A is abruptly and coordinately weakened. Double immunofluorescence staining of normal and dysplastic tissue showed that C4.4A colocalizes with the epithelial cell surface marker E-cadherin in the suprabasal cells and has a complementary expression pattern compared to the proliferation marker Ki-67. A prominent, but frequently intracellular, C4.4A expression reappeared in tumor cells located at the invasive front and local lymph node metastases. Because C4.4A was reported previously to be a putative laminin-5 (LN5) ligand, and both proteins are expressed by invasive tumor cells, we analyzed the possible coexpression of C4.4A and the gamma 2-chain of LN5 (LN5-gamma 2). Although these proteins are indeed expressed by either neighboring cancer cells or in a few cases even coexpressed by the same cells in the tumor front and metastases, we found no evidence for a general colocalization in the extracellular compartment by confocal microscopy. In conclusion, C4.4A is expressed during invasion and metastasis of human ESCC and may thus provide a new histological marker in this disease. PMID- 17849476 TI - Transforming growth factor-beta signaling in cancer invasion and metastasis. AB - Transforming growth factor-beta (TGF-beta) family members are polypeptides with dual tumor suppressive and oncogenic effects. They signal through serine/threonine kinase receptor complexes, which phosphorylate cytoplasmic mediators, the Smads. Upon phosphorylation, Smads translocate to the nucleus and associate with transcriptional coactivators or corepressors, and regulate the transcriptional activation of various TGF-beta responsive genes. In addition, TGF beta activates cellular mitogen-activated protein kinase signaling pathways, which crosstalk with Smad signaling and regulate growth, survival and motility of cells. During tumorigenesis, malignantly transformed cells often lose the response to the tumor suppressive effects of TGF-beta, which, in turn, starts to act as an autocrine tumor promoting factor by enhancing cancer invasion and metastasis. In this review, we summarize current view on the role of TGF-beta signaling in tumorigenesis, with emphasis on cancer invasion and metastasis. On the basis of these recent observations, we discuss new therapeutic strategies targeting TGF-beta signaling at distinct levels as a basis for inhibiting tumor growth, angiogenesis, invasion and metastasis. PMID- 17849477 TI - Solid-phase synthesis of 4,8-disubstituted-8,9-dihydropyrazino[2,3-g]quinazolin 7(6H)-ones. AB - An approach for the solid-phase synthesis of 4,8-disubstituted-8,9 dihydropyrazino[2,3-g]quinazolin-7(6H)-ones from 4-chloro-7-fluoro-6 nitroquinazoline scaffold is described. A chemoselective reaction of resin-bound arylamines (3) with 4-chloro-7-fluoro-6-nitroquinazoline (8) yielded resin-bound 4-arylamino-7-fluoro-6-nitroquinazolines (4), which were reacted with amino acid methyl esters to afford the corresponding resin-bound compound (5). Following the reduction of nitro group and intramolecular cyclization of 5, resin-bound 4,8 disubstituted-8,9-dihydropyrazino[2,3-g]quinazolin-7(6H)-one (6) was yielded. The desired products (7) were obtained in good yields and purities after cleavage from the resin. PMID- 17849478 TI - Inhibition of autophosphorylation of epidermal growth factor receptor by a small peptide not employing an ATP-competitive mechanism. AB - Previously we found that short peptides surrounding major autophosphorylation sites of EGFR (VPEY(1068)INQ, DY(1148)QQD, and ENAEY(1173)LR) suppress phosphorylation of purified EGFR to 30-50% at 4000 microM. In an attempt to improve potencies of the peptides, we modified the sequences by substituting various amino acids for tyrosine or by substituting Gln and Asn for Glu and Asp, respectively. Among the modified peptides, Asp/Asn- and Glu/Gln-substitution in DYQQD (NYQQN) and ENAEYLR (QNAQYLR), respectively, improved inhibitory potencies. The inhibitory potency of NYQQN was not affected by the concentration of ATP, while that of QNAQYLR was affected. Docking simulations showed different mechanisms of inhibition for the peptides: inhibition by binding to the ATP binding site (QNAQYLR) and inhibition by binding to a region surrounded by alphaC, the activation loop, and the catalytic loop and interfering with the catalytic reaction (NYQQN). The inhibitory potency of NYQQN for insulin receptor drastically decreased, whereas QNAQYLR inhibited autophosphorylation of insulin receptor as well as EGFR. In conclusion, NYQQN is not an ATP-competitive inhibitor and the binding site of this peptide appears to be novel as a tyrosine kinase inhibitor. NYQQN could be a promising seed for the development of anti cancer drugs having specificity for EGFR. PMID- 17849479 TI - Comparison of cystometric methods in female rats. AB - AIMS: Rat cystometry is a common model used to investigate urinary storage and voiding function. The effect of cystometric instrumentation in rat studies might be a source of deviation from normal physiologic responses. We hypothesized that transurethral catheterization would produce obstruction-related changes, and that suprapubic catheterization would limit volume-related functions as well as disrupt normal urothelial sensory function. We investigated the influence of transurethral and suprapubic catheterization on storage and voiding in the rat model. METHODS: Three groups of female SD rats 250-300 g under urethane anesthesia were studied. Cystometric and pseudoaffective responses to physiologic voiding with and without suprapubic catheter placement, and cystometry via suprapubic and transurethral catheterization were studied. RESULTS: In free voiding animals, per-void volume was 1.8 +/- 0.2 ml with an average flow rate of 0.18 ml/sec, and intercontraction interval (ICI) 60 min. Suprapubic catheterization decreased the ICI and per-void volume consistent with capacity reduction. Suprapubic cystometry did not significantly alter parameters compared to voiding except for a shortened ICI. Bladder pressures and somatic responses were increased, and urine flow impaired by transurethral cystometry. Terazosin did not significantly improve voiding parameters. CONCLUSIONS: Other than volume related parameter changes probably related to surgical compromise of bladder capacity, suprapubic catheterization does not alter the cystometric and physiologic responses to voiding when compared to normal, uninstrumented voiding. Transurethral cystometry appears to be obstructive and may activate nociceptive reflexes. For this reason, whenever possible, urodynamic testing using the rat model should employ suprapubic catheterization. PMID- 17849480 TI - On the origin of bladder sensing: Tr(i)ps in urology. AB - The mammalian TRP family consists of 28 channels that can be subdivided into 6 different classes: TRPV (vanilloid), TRPC (canonical), TRPM (Melastatin), TRPP (Polycystin), TRPML (Mucolipin), and TRPA (Ankyrin). TRP channels are activated by a diversity of physical (voltage, heat, cold, mechanical stress) or chemical (pH, osmolality) stimuli and by binding of specific ligands, enabling them to act as multifunctional sensors at the cellular level. Currently, a lot of scientific research is devoted to these channels and their role in sensing mechanisms throughout the body. In urology, there's a growing conviction that disturbances in afferent (sensory) mechanisms are highly important in the pathogenesis of functional problems. Therefore, the TRP family forms an interesting new target to focus on. In this review we attempt to summarize the existing knowledge about TRP channels in the urogenital tract. So far, TRPV1, TRPV2, TRPV4, TRPM8, and TRPA1 have been described in different parts of the urogenital tract. Although only TRPV1 (the vanilloid receptor) has been extensively studied so far, more evidence is slowly accumulating about the role of other TRP channels in the (patho)physiology of the urogenital tract. PMID- 17849481 TI - A mouse model of simulated birth trauma induced stress urinary incontinence. AB - AIMS: To facilitate future applications of transgenic or knockout technologies in studies of simulated birth trauma induced stress urinary incontinence (SUI), we aimed to create a mouse model of SUI and explore the possible pathogenesis of this condition. METHODS: Thirty female C57BL/6 mice were randomly distributed into five groups. Four groups underwent vaginal distention (VD) for 1 hr, using a modified 6-Fr. Foley catheter with a balloon dilated to 0.3, 0.2, or 0.1 ml or sham distention. Four days after VD, all mice underwent leak-point pressure (LPP) measurement via an implanted suprapubic tube (SPT). The normal control group only had SPT placement and LPP measurement. After sacrifice, the urethras of the mice were harvested for routine histological examination and nerve staining. RESULTS: LPPs were significantly lower in groups after VD with 0.3- or 0.2-ml balloon than in control and sham distention groups (10.29 +/- 6.70, 14.65 +/- 6.51, 37.78 +/- 5.10, and 30.30 +/- 5.30 cm H(2)O, respectively). There were no significant differences in LPP between control and sham groups. Histology showed no significant differences in urethral striated muscle among the five groups. The density of immunoreactive neurofilaments in the urethra decreased after VD with 0.3- or 0.2-ml balloon. CONCLUSION: As a model of birth trauma, VD can induce SUI in female mice, the severity of which is related to intravaginal balloon size. Partial urethral denervation plays a plausible role in the pathogenesis of SUI. This novel mouse model could be used for further mechanistic studies of female SUI. PMID- 17849482 TI - Prophylactic antibiotics in urodynamics: a systematic review of effectiveness and safety. AB - AIMS: To assess the effectiveness and safety of administering prophylactic antibiotics in reducing the risk of urinary tract infection (UTI) after urodynamic studies (UDS). METHODS: The CENTRAL, MEDLINE, EMBASE, CINAHI, LILIACS (up to January 2007), TRIP database, The National Library for Health, the citation lists of review articles, conference abstracts (2004-2006) and hand search of reference lists to identify relevant reviews and articles. Randomised controlled trials (RCTs) comparing effectiveness of prophylactic antibiotics with placebo or nothing in reducing bacteriologically proven UTI after invasive cystometry were included. Two reviewers extracted data independently and the results were expressed as peto odds ratio with 95% confidence intervals using fixed effects model in ReV Man 4.2.8 software. RESULTS: Eight RCTs with 995 patients were included. The majority of the patients were female. The studies were methodologically poor. The primary outcome in all but one study was newly acquired infection defined as colony count >10(5)/ml in urine tested post UDS. On meta-analysis, there was 40% reduction in the risk of significant bacteriuria with administration of prophylactic antibiotics (Peto odds ratio 0.39; 95% confidence interval 0.24-0.61). The antibiotics used differed in dose, type and duration. One minor skin rash and one major anaphylactic reaction requiring steroid injection therapy was reported in the treatment group. One would need to give prophylactic antibiotics to 13 individuals undergoing UDS to prevent one significant bacteriuria of unknown clinical significance. CONCLUSION: The use of prophylactic antibiotics in urodynamics reduces the risk of significant bacteriuria. PMID- 17849483 TI - alpha-Amido boronic acids: a synthetic challenge and their properties as serine protease inhibitors. AB - This review includes a personal account of the history of the development of the alpha-amido boronic acid synthesis and related chemistry in the author's laboratory, as well as a review of some of the more significant developments that have occurred elsewhere more recently. The simple initial target, suggested by biochemist G. E. Lienhard, proved much more elusive to reach than anticipated. The circuitous effort that ultimately revealed the deceptively simple successful route, for which there is still no alternative, will be described. The properties of these compounds as enzyme inhibitors will be described very briefly. More extensive reviews of the enzyme inhibiting properties of alpha-amido boronic acids have appeared recently. PMID- 17849485 TI - Flow cytometric lymphocyte subset enumeration: 10 years of external quality assessment in the Benelux countries. AB - A biannual external quality assessment (EQA) scheme for flow cytometric lymphocyte immunophenotyping is operational in the Benelux countries since 1996. We studied the effects of the methods used on assay outcome, and whether or not this EQA exercise was effective in reducing between-laboratory variation. Eighty test samples were distributed in 20 biannual send-outs. Per send-out, 50-71 participants were requested to enumerate CD3+, CD4+, and CD8+ T cells, B cells, and NK cells, and to provide methodological details. Participants received written debriefings with personalized recommendations after each send-out. For this report, data were analyzed using robust multivariate regression. Five variables were associated with significant positive or negative bias of absolute lymphocyte subset counts: (i) platform methodology (i.e., single-platform assays yielded lower CD4+ and CD8+ T-cell counts than did dual-platform assays); (ii) sample preparation technique (i.e., assays based on mononuclear cells isolation yielded lower T-cell counts than those based on red cell lysis); (iii) gating strategies based on CD45 and sideward scatter gating of lymphocytes yielded higher CD4+ T-cell counts than those based on "backgating" of lymphocytes guided by CD45 and CD14); (iv) stabilized samples were generally associated with higher lymphocyte subset counts than nonstabilized samples; and (v) laboratory. Platform methodology, sample stabilization, and laboratory also affected assay variability. With time, assay variability tended to decline; this trend was significant for B-cell counts only. In addition, significant bias and variability of results, independent of the variables tested for in this analysis, were also associated with individual laboratories. In spite of our recommendations, participants tended to standardize their techniques mainly with respect to sample preparation and gating strategies, but less with absolute counting techniques. Failure to fully standardize protocols may have led to only modest reductions in variability of results between laboratories. PMID- 17849486 TI - Calibration standards for antigen quantification in CLL. PMID- 17849487 TI - Dystonin/Bpag1--a link to what? AB - The dystonin/Bpag1 cytoskeletal interacting proteins play important roles in maintaining cytoarchitecture integrity in skin and in the neuromuscular system. The most profound phenotype observed in the dystonin mutant dystonia musculorum (dt) mice is a severe movement disorder, attributed in large part to sensory neuron degeneration. The molecular basis for this phenotype is currently not clear, despite several studies indicating possible causes for the pathology in dt mice. Complicating the picture of what essential dystonin functions are lost in dt mice is the fact that our understanding of the very nature of what dystonin is has evolved greatly over the past decade. Elucidating the roles of dystonin most relevant to neuronal function and survival should help to shed light on some of the common mechanisms underlying neurodegeneration. PMID- 17849488 TI - Developmental toxicity and uterotrophic studies with di-2-ethylhexyl terephthalate. AB - BACKGROUND: These studies were conducted to evaluate the potential adverse effects of di-2-ethylhexyl terephthalate (DEHT) exposure on in utero development in mice and rats. In addition, a uterotrophic assay for estrogenic activity was conducted in sexually immature rats. METHODS: In the developmental toxicity studies, diet containing DEHT was fed to four groups of mated female Crl:CD(SD)IGS BR rats (25/group) from gestation day (GD) 0-20 or Crl:CD1(ICR) mice (25/group) from GD 0-18. Concentrations within the feed were 0, 0.3, 0.6, and 1.0% for the rats and 0, 0.1, 0.3, and 0.7% for the mice. Laparohysterectomies were carried out on the last day of exposure and the numbers of fetuses, early and late resorptions, total implantations, and corpora lutea were recorded. The fetuses were weighed, sexed, and examined for external, visceral and skeletal malformations, and developmental variations. The dose rate from dietary DEHT exposure was 0, 226, 458, and 747 mg/kg/day in the rats and 197, 592, and 1382 mg/kg/day in the mice for the control, low, mid, and high exposure groups, respectively. RESULTS: DEHT exposure did not affect clinical observations. A slight reduction in body weight gain was noted in the high-dose level rat group; the remaining groups were unaffected. At necropsy, increased liver weights were noted in the high-dose rat group and the mid- and high-dose mouse groups. Mean numbers of implantation sites and viable fetuses, mean fetal weights, and mean litter proportions of preimplantation loss, early resorptions, late resorptions, and fetal sex ratios were unaffected by DEHT exposures. No test article-related malformations or variations were observed at any concentration level in the rat and mouse developmental toxicity studies. In the uterotrophic assay for estrogenic activity, sexually immature female rats received oral gavage doses 20, 200, or 2000 mg DEHT/kg bw/day from postnatal day (PND) 19-21. A slight reduction in rate of body weight gain was noted on the first day of dosing in the high dose group, but no other indications of toxicity were evident. DEHT exposure did not affect wet or blotted uterine weight parameters in any of these dose groups. The NOEL for developmental toxicity in rats was 747 mg/kg/day and 1382 mg/kg/day in mice. The NOEL for estrogenic activity was 2000 mg/kg/day. The NOEL for maternal toxicity was 458 mg/kg/day in rats and 197 mg/kg/day in mice. CONCLUSIONS: The lack of adverse developmental effects with DEHT exposure are in contrast to the adverse developmental effects noted after di-2-ethylhexyl phthalate (DEHP) exposure. The difference between the effects noted with the ortho-constituent (DEHP) and the lack of effects reported with the para constituent (DEHT) is due most likely to differences in metabolism and the formation of the stable monoester, mono-2-ethylhexyl phthalate (MEHP) from the DEHP moiety. PMID- 17849490 TI - Inferential testing for linkage with GENEHUNTER-MODSCORE: the impact of the pedigree structure on the null distribution of multipoint MOD scores. AB - The asymptotic distribution of [MOD] scores under the null hypothesis of no linkage is only known for affected sib pairs and other types of affected relative pairs. We have extended the GENEHUNTER-MODSCORE program to allow for simulations under the null hypothesis of no linkage to determine the empirical significance of MOD-score results in general situations. We performed simulations with families of different size (one million replicates of 500 families per simulation setting) to thoroughly investigate the impact of the pedigree size on the null distribution of multipoint MOD scores. It is shown that the distribution is dependent on the size and structure of the pedigrees under study. By performing simulations in the context of MOD-score analysis, our new tool efficiently explores the linkage data in a comprehensive way and also provides a valid method to inferentially test for linkage. PMID- 17849491 TI - A principal components regression approach to multilocus genetic association studies. AB - With the rapid development of modern genotyping technology, it is becoming commonplace to genotype densely spaced genetic markers such as single nucleotide polymorphisms (SNPs) along the genome. This development has inspired a strong interest in using multiple markers located in the target region for the detection of association. We introduce a principal components (PCs) regression method for candidate gene association studies where multiple SNPs from the candidate region tend to be correlated. In this approach, the total variance in the original genotype scores is decomposed into parts that correspond to uncorrelated PCs. The PCs with the largest variances are then used as regressors in a multiple regression. Simulation studies suggest that this approach can have higher power than some popular methods. An application to CHI3L2 gene expression data confirms a significant association between CHI3L2 gene expression level and SNPs from this gene that has been previously reported by others. PMID- 17849492 TI - Empirical significance values for linkage analysis: trait simulation using posterior model distributions from MCMC oligogenic segregation analysis. AB - Variance-components (VC) linkage analysis is a powerful model-free method for assessing linkage, but the distribution of VC logarithm of the odds ratio (LOD) scores may deviate substantially from the assumed asymptotic distribution. Typically, the null distribution of the VC-LOD score and other linkage statistics has been estimated by generating new genotype data independently of the trait data, and computing a linkage statistic for many such marker-simulated data sets. However, marker simulation is susceptible to errors in the assumed marker and map model and is computationally intensive. Here, we describe a method for generating posterior distributions of linkage statistics through simulation of trait data based on the original sample and on results from an initial scan using a Bayesian Markov-chain Monte Carlo (MCMC) approach for oligogenic segregation analysis. We use samples of oligogenic trait models taken from the posterior distribution to generate new samples of trait data, which were paired with the original marker data for analysis. Empirical P-values obtained from trait and marker simulation were similar when derived for several strong linkage signals from published linkage scans, and for analysis of data with a known, simulated, trait model. Furthermore, trait simulation produces the expected null distribution of VC-LOD scores and is computationally fast when marker identity-by-descent estimates from the original data could be reused. These results suggest that trait simulation gives valid estimates of statistical significance of linkage signals. Finally, these results also demonstrate the feasibility of obtaining empirical significance levels for evaluating Bayesian oligogenic linkage signals with either marker or trait simulation. PMID- 17849494 TI - Porphyrin light-harvesting arrays constructed in the recombinant tobacco mosaic virus scaffold. AB - We have demonstrated the construction of multiple porphyrin arrays in the tobacco mosaic virus (TMV) supramolecular structures by self-assembly of recombinant TMV coat protein (TMVCP) monomers, in which Zn-coordinated porphyrin (ZnP) and free base porphyrin (FbP) were site-selectively incorporated. The photophysical properties of porphyrin moieties incorporated in the TMV assemblies were also characterized. TMV-porphyrin conjugates employed as building blocks self assembled into unique disk and rod structures under the proper conditions as similar to native TMV assemblies. The mixture of a ZnP donor and an FbP acceptor was packed in the TMV assembly and showed energy transfer and light-harvesting activity. The detailed photophysical properties of the arrayed porphyrins in the TMV assemblies were examined by time-resolved fluorescence spectroscopy, and the energy transfer rates were determined to be 3.1-6.4x10(9) s(-1). The results indicate that the porphyrins are placed at the expected positions in the TMV assemblies. PMID- 17849495 TI - Supramolecular assembly of zinc salphen complexes: access to metal-containing gels and nanofibers. PMID- 17849496 TI - Structure of the Homoleptic Thorium(IV) Aqua Ion [Th(H2O)10]Br4. PMID- 17849497 TI - Regio- and enantioselective direct oxyamination reaction of aldehydes catalyzed by alpha,alpha-diphenylprolinol trimethylsilyl ether. PMID- 17849498 TI - MRI with diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) assessment in the evaluation of normal and abnormal fetal kidneys: preliminary experience. AB - OBJECTIVE: To investigate apparent diffusion coefficient (ADC) mapping with the measurement of renal tissue ADC value of normal and pathological fetal kidneys at various gestational ages (GAs). METHODS: Fifty pregnant women underwent magnetic resonance images (MRI) after ultrasound (US) for suspected fetal genitourinary disorders (16) or for suspected disorders in other organs (34). A multiplanar study of urinary system was obtained by using conventional T2-weighted sequences and echo planar imaging (EPI); Diffusion-weighted images and ADC maps were evaluated. The renal tissue ADC value was measured for all normal and abnormal fetuses and related to GA. RESULTS: MRI confirmed urinary anomalies in 15 fetuses [2 renal developmental variants, 2 nephropathies, 4 multicystic dysplastic kidneys (MCDK), 7 renal tract dilatations] and detected normal kidneys in the remaining 35 fetuses. Normal renal parenchyma showed bright signal on diffusion weighted images with ADC values ranging from 1,065 to 1,327 microm(2)/s with a tendency to decrease over GA. A pathological ADC was detected in cases of bilateral MCDK, huge dilatations and in cases of nephropathies. CONCLUSION: Diffusion-weighted imaging (DWI) with ADC mapping can be used in the evaluation of fetal renal parenchyma and may become a tool of assessing function of the fetal kidney by means of measurement of renal tissue ADC values. PMID- 17849499 TI - Chromosome topology in normal and aneuploid blastomeres from human embryos. AB - OBJECTIVES: To find whether chromosomes 13, 16, 18, 21, 22, X and Y in blastomeres of human embryos are nonrandomly localized, whether their aneuploidy affects their localization and if eventual early inactivation of chromosome X with peripheral localization is present. METHODS: Relative distances from the nucleus center and edge of 1,198 fluorescence in situ hybridization signals in 98 human blastomeres were measured in digital images for comparison with a mathematical model of random distribution in spherical nucleus. RESULTS: Comparison with the mathematical model revealed that localization of chromosomes 13, 16, 21, 22, X and Y in normal and aneuploid blastomeres and that of chromosome 18 in normal blastomeres was not significantly different from random distribution. Similarly, chromosome X in blastomeres with more than one X did not appear to have a preferential localization. Only chromosome 18 in aneuploid blastomeres was differently distributed (p < 0.0001) with a shift to the nuclear periphery (p =or < 0.0001). CONCLUSIONS: Peripheral localization of chromosome 18 in aneuploid blastomeres is related to embryo aneuploidy. Conversely, a peripheral localization of the inactive X chromosome was not found in blastomeres from 3-4 day old embryos. These results open the possibility to improve embryo selection after pre-implantation diagnosis. PMID- 17849500 TI - Prenatal diagnosis of a 9q34.3 microdeletion by array-CGH in a fetus with an apparently balanced translocation. AB - OBJECTIVES: Use high-resolution genome analysis to clarify the genomic integrity in a fetus with a cytogenetically balanced translocation t(2;9)(q11.2;q34.3). METHODS: High resolution molecular cytogenetic analyses including G-banded chromosome analysis, fluorescence in situ hybridization (FISH), and array comparative genomic hybridization (CGH) were performed on cultured cells, and DNA extracted from chorionic villus sample (CVS), amniotic fluid cells and fetal tissue. In addition, a custom fosmid-based tiling path 9q34.3 microarray with a resolution of 35-40 kb was used for array-CGH. RESULTS: GTG-banding analysis showed an apparently balanced de novo translocation between the long arms of chromosomes 2 and 9; t(2;9)(q11.2;q34.3). Array-CGH using a targeted chromosomal microarray analysis (CMA) uncovered a submicroscopic deletion of the subtelomeric region of 9q34.3 revealing the unbalanced nature of the rearrangement. These results were confirmed independently by FISH. The deletion was delimited to 2.7 Mb in size using the 9q34.3 fosmid-based tiling path array-CGH. CONCLUSION: Array CGH is a powerful tool for rapid detection of genomic imbalances associated with microdeletion/duplication syndromes and for the evaluation of de novo apparently balanced translocation to enable high-resolution genomic analysis at the breakpoints. Prenatal diagnosis of chromosomal rearrangements involving dosage sensitive genomic regions is an important adjuvant to prenatal care and provides more accurate information for counseling and informed decision making. PMID- 17849501 TI - Comment on 'Estimation and prediction of the HIV-AIDS-epidemic under conditions of HAART using mixtures of incubation time distributions' by S. H. Heisterkamp, R. de Vries, H. G. Sprenger, G. A. A. Hubben, M. J. Postma, Statistics in Medicine, DOI: 10.1002/sim.2974. PMID- 17849502 TI - Optimal phase I dose-escalation trial designs in oncology--a simulation study. AB - In phase I oncology trials conducted over the past few decades, the maximum tolerated dose (MTD) has usually been estimated by the traditional escalation rule (TER), which traces back to 1973. In the meantime, new methods have been proposed which hope to estimate the true MTD more precisely than the TER while using less patients. In this simulation study, TER is compared with the accelerated titration dose design (ATD), two up-and-down designs (biased coin design, r-in-a-row (RIAR)), the maximum likelihood version of the continual reassessment method (CRML), and a Bayesian method that is implemented in the software Bayesian ADEPT (assisted decision-making in early phase trials). Each design was applied to 50,000 simulated studies. The designs were then compared for accuracy in detecting the true MTD (which is known here), while taking into account the average number of patients and toxicities per run. In terms of accuracy, ADEPT outperformed the other methods in the scenario with medium toxicity and was close to the best methods in the low and high toxic scenarios. The average number of patients needed per run was the lowest for TER in the scenario with low toxicity and for ADEPT in the remaining scenarios. The longer the escalation path to the target region of the MTD, the more the difference in the average number of patients per run pronounced between TER and ADEPT. TER induced least toxicities in all scenarios. ADEPT turned out to be quick and accurate in determining the MTD, while TER was the safest but least accurate method. CRML was as accurate as TER, and the up-and-down designs did not excel. Bayesian ADEPT is considered a valuable tool for the conduct of phase I dose escalation trials in oncology, but careful preparation is indispensable before its practical use. PMID- 17849504 TI - Determination and pharmacokinetic study of norcantharidin in human serum by HPLC MS/MS method. AB - A sensitive, simple and selective high-performance liquid chromatography-tandem mass spectrometry method was developed and applied to the determination of norcantharidin concentration in human serum. Norcantharidin (NCTD) and cyclophosphamide (IS) in serum were extracted with acetone, separated on a C18 reversed-phase column, gradiently eluted with a mobile phase of acetonitrile water containing 2 mm ammonium acetate and 0.1% formic acid (pH 3), ionized by positive ion pneumatically assisted electrospray and detected in the multi reaction monitoring mode using precursor-->product ions of m/z 169.3-->123.1 for NCTD and 261.2-->140.2 for IS, respectively. The linear range of the calibration curve for NCTD was 2.5-50 ng/mL, with a lowest limit of quantification of 2.5 ng/mL, and the intra/inter-day RSD was less than 10%. The method was suitable for determination of low NCTD concentration in human serum after therapeutic oral doses, and has been successfully used for pharmacokinetic studies in healthy Chinese volunteers. PMID- 17849503 TI - GSK3 promotes arsenite-induced apoptosis via facilitation of mitochondria disruption. AB - Arsenic is an environmental toxicant that recently has been shown to have anticancer activity against a number of types of cancer cells by inducing apoptosis. Glycogen synthase kinase-3 (GSK3), a serine/threonine kinase, is an important pro-apoptotic signaling enzyme. Although GSK3 has been shown to promote apoptosis caused by a wide variety of insults, a role for GSK3 in arsenic-induced apoptosis has not yet been identified. Investigation of the involvement of GSK3 in arsenite-induced apoptosis demonstrated that arsenite induced apoptosis in SH SY5Y human neuroblastoma cells, activating the executioner caspase-3 which caused cleavage of poly-ADP ribose-polymerase (PARP). Two selective GSK3 inhibitors, lithium and SB216763, attenuated caspase-3 activation and PARP cleavage induced by arsenite treatment indicating that GSK3 contributed to arsenite-induced apoptosis. Apoptotic signaling following exposure to arsenite involved cytochrome C release from mitochondria, and this was reduced by inhibition of GSK3 indicating that GSK3 promotes arsenite-induced apoptotic signaling upstream of mitochondrial disruption. Moreover, arsenite induced the translocation of Bax and p53 to the mitochondria and the activation-associated oligomerization of Bax, and these crucial events were reduced by inhibition of GSK3, indicating that GSK3 promotes arsenite-induced apoptosis by facilitating signals leading to mitochondrial apoptotic events. Taken together, the findings from this study reveal that GSK3 promotes arsenite-induced apoptosis by facilitating signaling leading to disruption of mitochondria. PMID- 17849505 TI - Determination of glucosamine in horse plasma by liquid chromatography tandem mass spectrometry. AB - Glucosamine is an amino sugar involved in the biosynthesis of glycosylated proteins and lipids. Recently, with increased public interest in natural products medicine, glucosamine has been widely used to treat osteoarthritis, even though demonstrations of its actual efficacy remain relatively unknown. Information related to the pharmcokinetics of glucosamine is sparse. A recent analytical method published used 13C-glucosamine as an internal standard to analyse study samples. The method lacked accuracy owing to an important natural isotopic contribution of glucosamine to 13C-glucosamine ion abundance. This manuscript describes a simple method to quantify glucosamine in horse plasma. Glucosamine was extracted by protein precipitation with acetonotrile containing 0.1% formic acid. The chromatography was performed on a Agilent Hypersil-ODS 100x2.1 mm column with a mobile phase composed of acetonitrile and 0.5% formic acid in water (45:55) at a flow rate of 0.3 mL/min. A linear (1/x) relationship was used to perform the calibration over an analytical range of 10-1000 ng/mL. The inter batch precision and accuracy ranged from 5.3 to 11.3% and from 87.8 to 107.2% in horse plasma, respectively. The mean endogenous level of glucosamine in horse plasma was 14.4 ng/mL (n=6). This LC-ESI/MS/MS method for the determination of glucosamine in horse plasma provided results within generally accepted criteria used for bioanalytical assay. PMID- 17849506 TI - Simultaneous determination of dipyridamole and salicylic acid in human plasma by high performance liquid chromatography-mass spectrometry. AB - A sensitive, rapid and simple high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) method for simultaneous determination of dipyridamole and salicylic acid in human plasma has been developed and validated. After the addition of diazepam and rosiglitazone as internal standard (IS), plasma samples were prepared by liquid-liquid extraction followed by an isocratic elution with methanol:2 mM ammonium acetate buffer (pH 4.25; 70/30, v/v) on a Shimadzu VP-ODS C(18) column (5 microm, 150 x 2.0 mm I.D.). Detection was performed on a quadrupole mass spectrometer with ESI interface operating in the positive-ion mode for dipyridamole and negative-ion mode for salicylic acid. Calibration curves were linear (r(2) > 0.99) over the concentration range 10-2500 ng/mL for dipyridamole and 30-4000 ng/mL for salicylic acid with acceptable accuracy and precision, respectively. The intra- and inter-batch precisions were less than 15% of the relative standard deviation. The limits of detection of dipyridamole and salicylic acid were 1 and 15 ng/mL, respectively. The validated HPLC-ESI-MS method was successfully applied to a preliminary pharmacokinetic study of fixed-dose combination of sustained-release dipyridamole/aspirin in Chinese healthy male volunteers. PMID- 17849507 TI - Proceedings of the 34th International Congress on Electrocardiology and 48th International Symposium on Vectorcardiography, Istanbul, Turkey, 27-30 June 2007. PMID- 17849508 TI - Abstracts of the XXth Annual Research Meeting of the Kind-Philipp Foundation for Leukemia Research, June 6-9, 2007. PMID- 17849509 TI - Current awareness in human psychopharmacology. PMID- 17849510 TI - Hormones and heart disease in women: the timing hypothesis. AB - Largely on the basis of results from meta-analyses of observational studies, postmenopausal estrogen was widely prescribed to prevent coronary heart disease. However, epidemiologic studies, no matter how consistent and coherent, are not sufficient to recommend mass preventive therapy to healthy women. In fact, all three large clinical trials failed to confirm estrogen's expected cardiac protection. The most persistent explanatory hypothesis for the "trial failure" was the age of the participants, based on the thesis that estrogen in recently menopausal women could prevent the development of coronary artery plaque but, given to older women with vulnerable plaque, would have a null or even harmful effect. The timing hypothesis is plausible, but the prespecified subgroup analyses in both Women's Health Initiative trials showed no significant interaction with age or years since menopause. The best opportunity to test the timing hypothesis was lost when 1,000 Women's Health Initiative women younger than 60 years had coronary artery calcium scans to evaluate the effect of estrogen on plaque burden, but no women 60 years or over were similarly examined. Therefore, this ancillary study can examine the effect of estrogen treatment on coronary calcium in women younger than 60 years but will not be able to determine if the effect is different in older women. In the meantime, publicized statements in multiple venues have promoted the timing hypothesis as fact, confusing patients and physicians who do not realize that the hypothesis is stronger than the evidence. PMID- 17849511 TI - Bibliography. Current world literature. Forensic psychiatry. PMID- 17849512 TI - Abstracts of the 37th Annual Meeting of the International Continence Society, Rotterdam, The Netherlands, 20-24 August 2007. PMID- 17849513 TI - Abstracts of the 23rd International Conference on Pharmacoepidemiology and Therapeutic Risk Management, Quebec City, Canada, 19-22 August 2007. PMID- 17849514 TI - Editorial comment: factor that influence serum prostate-specific antigen levels in terms of maintaining quality within a PSA screening system. PMID- 17849515 TI - Across the arches of the years. PMID- 17849516 TI - Unravelling the genome: a review of molecular genetic research in schizophrenia. AB - BACKGROUND: Schizophrenia is a common and complex mental illness that affects approximately 1% of the population worldwide. Despite intensive research over the years, the aetiology and pathogenesis of schizophrenia is poorly understood. However, it has long been recognised that schizophrenia is highly familial suggesting a possible genetic aetiology. AIM: To review recent molecular genetic research in schizophrenia. METHODS: Medline and Embase search. RESULTS: Over the past decade, with the completion of the Human Genome Project, molecular genetic research has now identified a number of genes that are very likely to predispose to schizophrenia. CONCLUSION: This article discusses the methodologies that have been used to identify schizophrenia susceptibility genes and provides a review of recently identified genes thought to play a role in the pathogenesis of this illness. PMID- 17849517 TI - Construction-related eye injuries in Irish nationals and non-nationals: attitudes and strategies for prevention. AB - BACKGROUND: Construction-related ocular injuries are an important cause of vision loss but few studies on the incidence, epidemiology and nature of these injuries exist. AIMS: Due to the perceived increase in occupation-related eye injuries in non-nationals we aimed to investigate the nature of such injuries presenting to a single eye unit over a two-month period. METHODS: One hundred and fifty-five patients presenting to the accident and emergency department with construction related ocular injury were examined. RESULTS: Of 155 patients, 80 were Irish and 75 nonnational, of whom 60, 21.3 and 6.7% were Polish, Lithuanian and Romanian, respectively. Common causative factors included hammering, grinding, drilling and splash injury. Average rate of eyewear protection usage was 35%, with attendance at safety courses highest in Irish nationals. A penetrating eye injury rate of 4.9% overall was observed, all in non-nationals. CONCLUSION: Construction related ocular injury is a serious cause of visual loss in non-nationals. Greater adherence to safety regulations and training is required. PMID- 17849518 TI - The evolution of trauma services at Beaumont Hospital. AB - OBJECTIVE: To review and examine the epidemiology, severity and management of trauma admissions at the national neurosurgical teaching hospital. METHODS: An extensive audit of volume, type and severity of injury and the management requirements of the trauma population admitted to the hospital. RESULTS: The vast majority of severely injured patients were referred from outside the catchment area of the hospital with only 26% being admitted directly through the Emergency Department. As a consequence, 73% of patients arrived out of normal working hours, which posed problems in providing skilled trauma specialists. CONCLUSIONS: The management of patients with serious injury is complex. The large proportion of patients with critical injuries, some of whom were paediatric, highlighted the need for 24 h cover by senior trauma personnel and the provision of radiology and operating facilities to meet their needs. The inclusion of indicators of alterations in innate or adaptive immune responses may improve the predictive power of severity of injury scores. PMID- 17849519 TI - Introduction of an early pregnancy assessment unit: audit on the first 6 months of service. AB - BACKGROUND: Women experiencing bleeding in early pregnancy suffer considerable anxiety. Waiting for a considerable time for a diagnosis adds to their grievance. Early Pregnancy Assessment Unit (EPAU) is a dedicated service that provides quick and easy accessibility to diagnosis, treatment and support service. AIM: To monitor the first 6 months of the EPAU service in the Rotunda Hospital, to identify its shortcomings, so that we can ensure effective EPAU care in future. METHODS: A retrospective audit between July and December 2002 was performed. RESULTS: A majority of patients (83.4%) were self-referrals. All patients were seen between 1 and 3 h. In the miscarriage group, 218/278 (78.4%) was managed surgically by evacuation and a further 60/278 (21.6%) received conservative or medical treatment. Among 13 ectopic pregnancies, 5/13 (39%) had laparoscopic management. CONCLUSION: This clinic has enabled us to manage early pregnancy bleeding in an effective manner within a satisfactory time period. The high surgical intervention rate for miscarriages is highlighted to support the need for greater emphasis on medical and expectant management. PMID- 17849520 TI - Limited options: a report on GP access to services. AB - BACKGROUND: The Structure of Irish General Practice over 23 years was the third in a series of national studies that examined the development of general practice in 1982, 1992, and 2005. AIMS: This study analysed specific data from the 2005 survey to determine the types of services offered by GPs, and to examine the changes in access to diagnostic/treatment services from 1982 to 2005. METHODS: A questionnaire was sent to a stratified random sample of Irish GPs seeking information on their practice. RESULTS: 476 (87%) valid questionnaires were returned. The range of services offered by GPs had increased. Access to diagnostic/treatment services was limited, and varied considerably depending on the type of practice. Access to chest X-rays and skeletal X-rays had decreased. CONCLUSIONS: Access to existing services must be increased, and significant resources must be put into the development of dedicated primary care services. PMID- 17849521 TI - Transfusion requirements and outcomes in patients undergoing abdominal aortic surgery using intra-operative cell salvage. AB - BACKGROUND: Intraoperative cell salvage (ICS) is the recovery, anticoagulation, filtration and reinfusion of blood lost during surgery. The aim of this study is to determine the safety and efficacy of ICS in emergency and elective abdominal aortic surgery. METHODS: This study reviews volumes of blood loss, blood salvaged with ICS, allogenic blood requirements, and clinical outcomes in patients undergoing abdominal aortic surgery using ICS. RESULTS: Seventy-nine patients undergoing abdominal aortic surgery are included. Supplemental allogenic blood was not required in 45/79 (57%) of all patients. Transfusion with allogenic blood was not necessary in 41/63 (66%) of elective abdominal aortic aneurysm repairs. ICS was associated with no major complications. CONCLUSION: ICS is a safe procedure and substantially reduces the need for blood transfusion in patients undergoing abdominal aortic surgery. It may substantially alleviate shortages of allogenic blood and should be part of the armamentarium of vascular units. PMID- 17849522 TI - Are routine peritoneal fluid cultures during appendicectomy justified? AB - BACKGROUND: To determine the impact of obtaining routine peritoneal fluid cultures during appendicectomy, on the treatment and the clinical outcomes. METHODS: The case notes of 137 consecutive patients having appendicectomy, selected from the microbiology database over a period of 1 year were reviewed. The microorganisms in peritoneal cultures, selection of antibiotics and clinical outcomes were recorded. Patients were subdivided into two groups; group I: uncomplicated appendicitis and group II: complicated appendicitis. RESULTS: The study included 137 patients with a median age of 19 years. Cultures were obtained from 79.5% of patients (group I: 67/84, group II: 42/53). Cultures were positive in 28.3% (19/67) patients in group I and 69% (29/ 42) in group II. Wound infection (5.6%), prolonged ileus (7.5%) and intra-abdominal abscess (3.7%) were the recorded complications in group II. Antibiotics were modified in 3 out of 109 patients. CONCLUSION: Intra-operative peritoneal cultures during appendicectomy do not significantly contribute towards patient management. PMID- 17849523 TI - Practice patterns in flexor tendon repair. AB - BACKGROUND: There is a considerable volume of literature describing new and supposedly superior methods of flexor tendon repair. AIM: The purpose of this study was to assess the flexor tendon techniques currently used in the Republic of Ireland. METHODS: A postal survey was conducted of all consultant plastic surgeons and consultant orthopaedic surgeons who were members of the Irish Hand Surgery Society. RESULTS: The response rate was 90% (27/30). A simple running peripheral suture was used by 73% (P = 0.03) and the Kessler was the core suture of choice for 68% (P = 0.06). A significant number of respondents use non absorbable suture materials for core (P = 0.0028) and peripheral suture (P < 0.0001). Seventy-seven percent sutured the flexor sheath where possible (P = 0.009). CONCLUSIONS: Notwithstanding the proposed advantages of newer techniques, it is evident from this study that the two-stranded Kessler core and simple running peripheral suture remains the most popular flexor tendon repair, with sheath closure preferred by the majority of respondents. PMID- 17849524 TI - All that is hypogonadal in haemochromatosis is not due to iron deposition. AB - BACKGROUND: Hereditary haemochromatosis (HH) is an autosomal recessive condition resulting in excessive gastrointestinal absorption of iron, which may be deposited in various organs. Apart from diabetes, hypogonadism is the most common endocrinopathy associated with HH and is usually secondary to excess iron deposition in the anterior pituitary gland. AIMS AND METHODS: We present three patients with HH and hypogonadism. RESULTS: Careful clinical and biochemical analysis revealed that the hypogonadism was due to causes other than iron deposition. CONCLUSIONS: This series illustrates the importance of having a high degree of clinical suspicion, even when dealing with what may clinically appear to be a straight-forward clinical problem. PMID- 17849525 TI - Wilms' tumour in adults: a case report and review of the literature. AB - BACKGROUND: Wilms' tumour is a very rare adult malignancy representing 1% of adult renal tumours. It is however the most common renal tumour of childhood, and adult patients are treated in accordance with paediatric protocols. AIM: To review modern day management of adult Wilms' tumour. METHODS: We report a case of adult Wilms' tumour and discuss the management including the use of newer treatment modalities. RESULTS: Following diagnostic nephrectomy, our patient was treated with chemotherapy in accordance with North American paediatric protocols and PET scanning was used to diagnose early relapse. CONCLUSION: In the absence of randomised controlled data, central reporting of cases of adult Wilms' Tumour may help improve management. The incorporation of newer chemotherapeutic agents, high-dose therapy and PET scanning into treatment protocols should improve outcome for these patients. PMID- 17849526 TI - Acute dystonic reaction secondary to prochlorperazine use in the treatment of hyperemesis gravidarum. PMID- 17849527 TI - Early detection saves an elderly woman. PMID- 17849528 TI - The game of the name: terminology in clinical forensic medicine. PMID- 17849603 TI - Bereavement rituals in the Muscogee Creek tribe. AB - A qualitative, collective case study explores bereavement rituals in the Muscogee Creek tribe. Data from interviews with 27 participants, all adult members of the tribe, revealed consensus on participation in certain bereavement rituals. Common rituals included: (a) conducting a wake service the night before burial; (b) never leaving the body alone before burial; (c) enclosing personal items and food in the casket; (d) digging graves by hand; (e) each individual throwing a handful of dirt into the grave before covering, called giving a "farewell handshake"; (f) covering the grave completely by hand; (g) building a house over the grave; (h) waiting 4 days before burial; (i) using medicine/purification; and (j) adhering to socialized mourning period. Cultural values of family, community, religion, importance of the number 4, Indian medicine, and the meaning of death contributed to the development of these rituals. PMID- 17849604 TI - Does education matter? Major League Baseball players and longevity. AB - The authors used duration analysis to examine the longevity of Major League Baseball players. Using data on players who were born between 1945 and 1964, the authors found that the hazard rate of death for players who only attended high school was almost 2.0 times higher than those players who attended a 4-year university, evidence that the educaton [sic]-health link applies to professional athletes. Another important determinant of longevity was race. In addition, a player's body mass index was positively associated with a higher hazard of death. Compared with the general population, the death rate of baseball players was lower--the observed number of deaths in the dataset was only 31% of the expected number. Findings in this article are likely attributable to education being correlated with other variables that affect longevity, most likely intelligence and time preference. PMID- 17849605 TI - Letters from a suicide. AB - A linguistic analysis of a series of letters written by a young man who died by suicide to 1 friend over a period of 2 years prior to his death revealed several trends, including a decrease in negative emotion words and an increase in death words. The implication of these trends was discussed. PMID- 17849606 TI - Profiles of posttraumatic growth following an unjust loss. AB - The dominant model of posttraumatic growth (PTG) suggests that growth is precipitated by significant challenges to one's identity or to core assumptions that give one's life meaning, and develops as one goes through meaning-making or schema reconstruction processes. Other perspectives suggest, however, that such growth occurs by other means. We use a numerically aided phenomenological approach to elucidate common profiles of growth in a sample of 52 adults who lost a loved one in a traumatic mine explosion 8 years earlier. Of the three clusters extracted, 1 captured the essence of the PTG model, including threat to sense of self, meaning-making, and personal growth; 1 featured an inability to find meaning and an absence of growth; and 1 featured minimal meaning threat with modest growth. Those most likely to report PTG interpreted the experience as threat to self, with growth coming from development of new self-understanding. The data suggest that a better understanding of the processes of PTG may be realized by taking a more refined approach to the assessment of loss and growth, and by drawing distinctions between personal growth and benefits. PMID- 17849607 TI - [Deletion of spiramycin 3-O-acyltransferase gene from Streptomyces spiramyceticus F21 resulting in the production of spiramycin I as major component]. AB - Spiramycin (SP) belongs to the 16-member macrolide antibiotics. It contains three components,namely SP I, SP II and SP III, which differ structurally in the acylation moieties on the C3 of the lactone. The SP I component contains a hydroxyl group at C3. SP II, and SP III are formed by further acetylation or propionylation of the C3 of SP I, by the same 3-O-acyltransferase (3-O-AT) . The study focused on simplifying spiramycin components. Theoretically, disruption/deletion of the 3-O-AT gene will reduce/stop the acylation of SP I to SP II and SP III. In this study, degenerated primers were designed according to the conserved regions of 3-O-acyltransferase, MdmB and AcyA in the medicamycin and carbomycin producers of S. mycarofaciens and S. thermotolerans, respectively, and an 878bp DNA fragment was amplified from the spiramycin-producer of S. spiramyceticus F21. Blast analysis of the 878bp DNA fragment suggested that it encoded the 3-O-acyltransferase (3-0-AT, sspA) gene for spiramycin biosynthesis. The flanking regions of this 878bp DNA fragment were then amplified by single oligonucleotide-nested PCR, and a total of 4.3 kb DNA was obtained (3457nt among the 4.3kb fragment was sequenced, and deposited in GenBank DQ642742),covering the whole putative 3-O-acyltransferase gene, sspA. The sspA was then deleted from the S. spiramyceticus F21 genome by double cross-over homologous recombination, mediated by temperature-sensitive plasmid pKC1139. A comparison was done of the components of spiramycins produced by the sspA-deleted mutant strain with that of the parent strain by HPLC analysis, which showed that sspA-deleted mutant produced SP I (72%), SP II (18%), and SP III (9.6%), whereas parent strain produced SP I (7.8%), SP II (67%), and SP III (25%), respectively, demonstrating the role of ssp A in the acylation of SP I into SP II and SP III. The ssp A deleted mutant strain obtained in this study may be used for the production of SP I, or may serve as a good starter for the construction of spiramycin derivatives. PMID- 17849609 TI - A retrospective of atrial septal defect closure devices. PMID- 17849608 TI - Scientifically unsupported therapies in the treatment of young children with autism spectrum disorders. AB - Our understanding of ASD has changed over the past decades, and diagnostic tools have assisted in earlier identification and referral for intervention. Appropriate intervention appears to impact positively on overall outcome for a pervasive developmental disorder for which there is currently no known cure. Novel and controversial therapies will come and go, and therefore physicians should familiarize themselves with these interventions, as advice about these alternative approaches will be sought. Discussions of nontraditional therapies should include the placebo effect, possibly undesirable, or potentially dangerous outcomes of a treatment, and the importance of scientifically sound research studies of that treatment. Addressing the use of complementary and alternative therapies in families with medically-compromised or developmentally disabled children is crucial to providing complete care to the patient and in the maintenance of a medical home. PMID- 17849610 TI - Toward a description of deaf college students' written English: overuse, avoidance, and mastery of function words. AB - The use of function words in 135 essays written by deaf college underclassmen in developmental and credit-bearing English composition classes is described and compared with Standard English (SE) versions of teh same essay. If student and SE version were the same, this was considered mastery; if the student omitted a word, this was considered avoidance; and if the student added a word, this was considered overuse. The deaf students varied from SE more for function than for content words. They demonstrated low mastery of independent clause markers, demonstratives, third-person singular neuter pronouns, and modals related to possibility, but had relatively high mastery of the first-person singular; and some punctuation. These students strongly avoided some dependent clause markers, some demonstratives, the indefinite article, punctuation except for periods and commas, and the modal verbs may, might and should , but greatly overused other dependent clause markers, the second person and third-person pronouns, quantifiers, the verb do, and the modals could and will. They were also more likely to produce run-ons than fragments. PMID- 17849612 TI - Educational programs for deaf students. Schools and programs in Canada. PMID- 17849611 TI - Educational programs for deaf students. Schools and programs in the United States. PMID- 17849613 TI - Educational programs for deaf students. Postsecondary programs. PMID- 17849614 TI - University and college programs for personnel in deafness. PMID- 17849615 TI - Programs for deaf-blind children and adults. PMID- 17849617 TI - Research on deafness. Doctoral dissertations. PMID- 17849616 TI - Advocacy, professional, support, and rehabilitation programs. PMID- 17849618 TI - Accelerated partial breast irradiation as sole radiotherapy after breast conserving surgery for early stage breast cancer. PMID- 17849619 TI - Imogene M. King over the years. PMID- 17849620 TI - Madeleine Leininger over the years. PMID- 17849621 TI - The Theory of Caritative Caring: a vision. PMID- 17849622 TI - The power of one: confidence in our evolving future. PMID- 17849623 TI - Nursing research in 2050. PMID- 17849624 TI - What will count as evidence in the year 2050? PMID- 17849625 TI - A Human Becoming perspective on quality of life. PMID- 17849626 TI - Living nursing presence with soldiers returning from Iraq and Afghanistan: quality of life issues for returning soldiers. PMID- 17849627 TI - Quality of life issues in an acute health crisis. PMID- 17849628 TI - Quality of life issues in the student experience. PMID- 17849629 TI - Quality of life issues in nursing leadership. PMID- 17849630 TI - Imagining nursing practice: the Neumann Systems Model in 2050. PMID- 17849631 TI - Imagining nursing practice in the year 2050: through a Rogerian looking glass. PMID- 17849632 TI - The proper focus for FDA regulations: why the fundamental right to self preservation should allow terminally ill patients with no treatment options to attempt to save their lives. PMID- 17849633 TI - Low health literacy puts patients at risk. PMID- 17849634 TI - Top 25 women in healthcare. PMID- 17849635 TI - Maturational effects of the vestibular system: a study of rotary chair, computerized dynamic posturography, and vestibular evoked myogenic potentials with children. AB - Maturational effects were investigated in two age groups (N = 30 per group) of children with normal hearing sensitivity, using rotary chair (RC), computerized dynamic posturography (CDP), and vestibular evoked myogenic potential (VEMP) measures. Children recruited within the younger group were three through six years of age, and children within the older group were nine through eleven years of age. Data obtained for each pediatric group were compared with clinic and/or published adult normative data for each measure. Significant age effects were seen on many CDP subtests (sensory organization test and motor control test); VEMP latencies; and RC gain, phase, and step velocity measures. The results of this study demonstrate significant maturational effects from preschool age through adulthood and suggest that adult normative data may not be appropriate when interpreting pediatric test results. Since adult techniques should oftentimes not be utilized, a proposed test battery is described that may be efficiently utilized with pediatric patients. PMID- 17849636 TI - Short-term and long-term hearing aid benefit and user satisfaction: a comparison between two fitting protocols. AB - Currently published hearing aid fitting protocols recommend speech-in-noise testing and loudness measures, but it remains unclear how these measures affect hearing aid benefit and user satisfaction. This study compared two protocols in their effects on benefit and satisfaction. Protocol A included an electroacoustic analysis, real-ear measures, and hearing aid adjustments based on users' comments. Protocol B included all of Protocol A and a speech-in-noise test, loudness discomfort levels, and aided loudness. Thirty-two participants completed the Abbreviated Profile of Hearing Aid Benefit (APHAB) and the Satisfaction with Amplification in Daily Life (SADL) at 45 days and three months post-initial fitting. Fewer hearing aid adjustments were made to the hearing aids for participants fitted with Protocol B than participants fitted with Protocol A, but final gains were similar for both groups. Although similar APHAB scores were obtained for both protocols, SADL scores decreased between 45 days and three months for Protocol A. PMID- 17849637 TI - Evaluation of the subjective effect of middle ear implantation in hearing impaired patients with severe external otitis. AB - The subjective benefit of middle ear implantation was studied in a group of 23 hearing-impaired patients who could not use conventional hearing aids owing to severe chronic external otitis. Changes in hearing disability (Abbreviated Profile of Hearing Aid Benefit [APHAB]) and changes in quality of life (Glasgow Benefit Inventory [GBI]) were determined. Mean benefit value on the APHAB for the subscale Ease of Communication was close to the mean reference value for conventional hearing aids. For the subscales Reverberation and Background Noise, a poorer result was found. Individual analysis of the APHAB scores showed significant benefit in 12 out of the 23 patients. According to the GBI, 16 out of 17 patients reported that middle ear implantation had made a positive impact on their quality of life. It is concluded that middle ear implantation has a positive effect on hearing difficulties and quality of life in hearing-impaired subjects who cannot use conventional devices. The APHAB outcomes were not better than those reported for conventional devices. PMID- 17849638 TI - Hearing aid maximum output and loudness discomfort: are unaided loudness measures needed? AB - The purpose of this study was to evaluate a clinical protocol for setting hearing aid maximum output (MPO) in adult users. The protocol consisted of matching prescriptive targets for MPO followed by aided loudness validation and adjustment. Twenty-eight adults fit with multichannel hearing aids during the previous two years were recalled for unaided loudness measures. During the recall visit, unaided frequency-specific loudness discomfort levels were measured for frequencies between 250 and 3000 Hz. These values were converted to real-ear levels by adding individually measured real-ear dial differences. Real-ear saturation responses (RESR) were measured using a 90 dB pure-tone sweep and compared to the real-ear loudness discomfort levels. All participants completed the APHAB Aversiveness scale and Munro-Patel loudness questionnaire. A subset of participants (n = 20) completed the Profile of Aided Loudness. The average RESR UCL difference was -5.7 dB, and the maximum difference was 15 dB. For all but one participant, the average RESR values (.5-3 kHz) were either less than or no more than 5 dB above the LDLs, and the aided APHAB Aversiveness scores were below the 80th percentile. There were no significant correlations between the scores on the loudness questionnaires and the differences between RESR and LDL values. Results suggest that unaided LDL measures may be redundant if aided loudness validation measures are completed. PMID- 17849639 TI - Binaural interference in a child: a case study. AB - A case study of a child (KB) who demonstrated binaural interference is reported. KB wore unilateral amplification from 1.6 to 4.6 years of age, at which time word recognition scores under phones were markedly asymmetric, reflecting significantly better performance for the aided ear than the unaided ear, despite similar unaided pure-tone sensitivity. Suspecting the asymmetry in word recognition performance might be the result of auditory deprivation, bilateral amplification was prescribed at 4.6 years of age. Three months later, adverse changes in the child's behavior were reported. At 5.3 years, significant interaural asymmetry was noted in word-recognition scores under phones, in unilateral-aided word-recognition scores (90% vs. 36%), and in the bilateral aided score (56%), supporting the presence of binaural interference. PMID- 17849640 TI - The Words-in-Noise (WIN) test with multitalker babble and speech-spectrum noise maskers. AB - The Words-in-Noise (WIN) test uses monosyllabic words in seven signal-to-noise ratios of multitalker babble (MTB) to evaluate the ability of individuals to understand speech in background noise. The purpose of this study was to evaluate the criterion validity of the WIN by comparing recognition performances under MTB and speech-spectrum noise (SSN) using listeners with normal hearing and listeners with hearing loss. The MTB and SSN had identical rms and similar spectra but different amplitude-modulation characteristics. The performances by the listeners with normal hearing, which were 2 dB better in MTB than in SSN, were about 10 dB better than the performances by the listeners with hearing loss, which were about 0.5 dB better in MTB with 56% of the listeners better in MTB and 40% better in SSN. The slopes of the functions for the normal-hearing listeners (8-9%/dB) were steeper than the functions for the listeners with hearing loss (5-6%/dB). The data indicate that the WIN has good criterion validity. PMID- 17849641 TI - The ethics of withdrawal from study participation. AB - We investigated whether consent forms adhere to Federal Common Rule regulations pertaining to withdrawal from research, described the language of withdrawal provisions, and assessed differences in studies by withdrawal provisions. A random sample of 114 consent forms from a midwestern, academic medical center were examined for descriptive content of withdrawal parameters stated within consent forms. All consent forms included the required statement about withdrawal pursuant to the Code of Federal Regulations (CFR) 45 CFR (46.116(a)(8)), and all adhered to regulation 45 CFR (46.116(b)(4)) by including a statement that withdrawal will have no affect on care provided. Of 114 studies, thirty (26%) studies explicitly requested subjects/participants to engage in a further behavior before withdrawing from the study. Safety was mentioned in only 4 (13%) instances as the reason for an additional visit or test. None of the consent forms provided information about the consequences to the subject's health or well being by withdrawing from study participation. Consent forms generally conform to current regulations. Future research should examine subjects' experiences of withdrawing from research in order to help clinical investigators and Institutional Review Boards (IRBs) assess the extent to which consent forms indicate barriers to withdrawal and for compliance with Federal Common Rule regulations. PMID- 17849642 TI - Gender, racial, and ethnic disclosure in NIH K-Award funded diabetes and obesity clinical trials. AB - In 1993, the National Institutes of Health (NIH) passed The Revitalization Act (Subtitle B) which mandated that all NIH funded clinical trials have "appropriate representation" of minority and women subjects. Our aim was to evaluate the impact of the mandate by examining the reporting and inclusion of minority and female subjects into NIH K-Award funded clinical trials, addressing the minority predominant diagnoses of diabetes and clinical obesity. Using the CRISP search engine and PUBMED, we selected publications published by the National Institute on Aging (NIA) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) K-grant recipients during 1989-2004, associated with all the diabetes and obesity clinical trials. Studies were stratified into three timeline categories (1989-1993, pre-mandate; 1993-1996, post-mandate, and 1997-present, well past mandate) to evaluate trends in the recruiting of minorities and women before, during, and after the passing of the Revitalization Act. Of the 165 papers, only 37% disclosed race, a number that did not improve over time (p=.15), whereas 92% disclosed gender. Clinical trials that focused on females increased across the 3 timeframes (p < .001) for diabetes studies but not obesity studies. Overall, disclosure of race declined over the 3 timeframes whereas individually, the disclosure of African Americans improved. PMID- 17849643 TI - Comparison of conflict of interest policies and reported practices in academic medical centers in the United States. AB - The authors reviewed the conflict of interest policies of 9 academic medical centers in the United States and interviewed members of the Institutional Review Boards (IRBs) and Conflict of Interest Committees (COICs) at those institutions. They found that many institutions used processes for reporting and managing conflicts of interest that were more decentralized than the processes described in their policies. Also, most institutions had no clear and comprehensive policy to guide investigators regarding disclosure of conflicts of interest to potential research participants. Considerable differences in understanding of conflict of interest policies were observed between IRB and COIC officials. PMID- 17849644 TI - Embryonic, fetal and post-natal animal-human mixtures: an ethical discussion. PMID- 17849645 TI - Unity and variety of ethical principles: human dignity endangered. PMID- 17849646 TI - Harris on Quintavalle and the ethics of stem-cell research. PMID- 17849647 TI - Evidence-based practice: a reliable source to access interventions for youth risk behaviors. PMID- 17849648 TI - Vulnerable populations and health care disparities. PMID- 17849649 TI - The concept of vulnerability and the protection of human subjects of research. AB - This article provides an overview of the concept of vulnerability through the lens of the U.S. federal regulations for the protection of human subjects of research. General issues that emerge for nurse researchers working with regulated vulnerable populations are identified. Points of current controversy in the application of the regulations and current discourse about vulnerable groups are highlighted. Suggestions for negotiating the tension between federally regulated human subject requirements and the realities of research with vulnerable subjects are given. The limitations of the designation of vulnerable as a protection for human subjects will also be discussed. PMID- 17849650 TI - The usefulness of the community nursing practice model in grounding practice and research: narratives from the United States and Africa. AB - A community nursing practice (CNP) model is presented as the synthesis of a decade of experience of caring for persons and communities. Values form the basis of the model and provide the grounding for practice. Transcendent values of respect, caring, and wholeness are explicated in the actualizing values of primary health care: access, essentiality, empowerment, intersectoral collaboration, and community participation. Usefulness of the CNPM in providing a framework for community nursing practice at school-based community wellness centers in both the United States and Africa is described. Narratives of practice and research presented in the unique voice of three faculty members illuminate the model's values and paradigmatic view of person, nursing, community, and environment. These narratives provide insight into how the CNPM has served as a heuristic in the design of creative responses to calls for nursing in community nursing practice, education, and research. PMID- 17849651 TI - Resistance, health, and latent tuberculosis infection: Mexican immigrants at the U.S.-Mexico border. AB - Mexican immigrants living in the U.S.-Mexico border region are confronted with different national explanations about latent tuberculosis infection (LTBI) and preventive treatment. The purpose of this study was to explore how a group of Mexican immigrant women (N = 8) at risk of LTBI treatment failure interpreted and ultimately resisted LTBI preventive treatment. A critical ethnographic methodology, grounded in asymmetrical power relations that are historically embedded within the U.S.-Mexico border culture, was used to examine the encounters between the participants and the health care provider. The study findings are discussed from the perspective of women who experienced oppression and resistance in the U.S.-Mexico border region, providing an account of how Mexican immigrant women become entangled in U.S.-Mexico TB health policies and through resistance manage to assert control over health care choices. In the context of the U.S.-Mexico border region, health care professionals must be skilled at minimizing asymmetrical power relations and use methods that elicit immigrant voices in reconciling differences in health beliefs and practices. PMID- 17849652 TI - Evaluating the effect of teaching modules on underserved clients' perceived health. AB - Underserved individuals need comprehensive health care. Educational resources that meet health care needs can promote wellness. This descriptive study evaluated effects of preferred teaching modules on perceived health of underserved clients of a nurse-managed center. Participants (N = 101) were between 19 and 61 (M = 38.7); the majority was female (68.3%) with a high-school education (M = 12.17). Most participants (65%) identified health education as very important; 92% used at least one teaching module. Age, gender, and education were not related to importance of health education. Use of various teaching modules was positively correlated with perceived improved health (p < .05). Participants who used a combination of videos and pamphlets reported the greatest improvement (p < .000). PMID- 17849653 TI - NPSGs target anticoagulation therapy, patient deterioration. AB - Maintaining therapeutic levels is critical clinical component of anticoagulation therapy goal. Joint Commission does not mandate use of Rapid Response Teams in addressing patient deterioration. Regular review of performance and progress, proactive approach can keep you ahead of the curve. PMID- 17849654 TI - Solucient 'Top 100' hospital scores 'three-peat'. AB - Quality, safety focus must be driven by board and senior staff leadership. Set new targets and goals each year to ensure continuous improvement. Non-punitive culture of safety is necessary to encourage staff to report adverse events. PMID- 17849655 TI - Physician backing critical to QI turnaround. AB - Risk stratification tool helps staff avoid unnecessarily risky surgeries. Cardiologists take the lead, and help get surgeons on board with new approach. Hospital quality staff work side by side with consultants to implement initiative. PMID- 17849656 TI - Simple test can prevent pneumonia after a stroke. AB - Annual cost of pneumonia could be nearly $459 million. Doing swallow test could reduce likelihood of pneumonia by 50%. Despite benefits, best practice use is at discouragingly low levels. PMID- 17849657 TI - Link seen between working conditions, infections. AB - ICUs with higher staffing had lower incidence of central line-associated bloodstream infections. Overall work environment also directly affected patient safety outcomes. Cross-trained float nurses can be used to overcome staffing shortages. PMID- 17849658 TI - Sleeping better at night: investigators' experiences with certificates of confidentiality. PMID- 17849659 TI - Research participant safety and systems factors in general clinical research centers. PMID- 17849660 TI - Medical ethics' appropriation of moral philosophy: the case of the sympathetic and the unsympathetic physician. AB - Philosophy textbooks typically treat bioethics as a form of "applied ethics" i.e., an attempt to apply a moral theory, like utilitarianism, to controversial ethical issues in biology and medicine. Historians, however, can find virtually no cases in which applied philosophical moral theory influenced ethical practice in biology or medicine. In light of the absence of historical evidence, the authors of this paper advance an alternative model of the historical relationship between philosophical ethics and medical ethics, the appropriation model. They offer two historical case studies to illustrate the ways in which physicians have "appropriated" concepts and theory fragments from philosophers, and demonstrate how appropriated moral philosophy profoundly influenced the way medical morality was conceived and practiced. PMID- 17849661 TI - Selective appropriation, medical ethics, and health politics: the complementarity of Baker, McCullough, and me. AB - Baker and McCullough (2007) criticize a 1979 article by this author for insufficiently appreciating how physicians have appropriated ideas from moral philosophy. This rejoinder argues that the two articles are complementary. The 1979 article summarized evidence that leading physicians in the nineteenth and twentieth centuries appropriated ideas from moral philosophy and related disciplines that reinforced their political goals of self-regulation and dominance of the allocation of resources for health. In retrospect the 1979 article also urged bioethicists to appropriate ideas from other disciplines, including moral philosophy, which would contribute to improving the health of populations. PMID- 17849662 TI - Turning the history of medical ethics from its head onto its feet: a critical commentary on Baker and McCullough. AB - The paper provides a critical commentary on the article by Baker and McCullough on Medical Ethic's Appropriation of Moral Philosophy. The author argues that Baker and McCullough offer a more "pragmatic" approach to the history of medical ethics that has the potential to enrich the bioethics field with a greater historical grounding and sound methodology. Their approach can help us to come to a more nuanced understanding about the way in which medical ethics has connected, disconnected, and reconnected with philosophical ideas throughout the centuries. The author points out that Baker and McCullough's model can run the danger of overemphasizing the role of medical ethicists whilst marginalizing the influence of philosophers and of other historical actors and forces. He critically reviews the two case studies on which Baker and McCullough focus and concludes that scholars need to bear in mind the levels of uncertainty and ambivalence that accompany the process of transformation and dissemination of moral values in medicine and medical practice. PMID- 17849663 TI - How to appropriate appropriately: a comment on Baker and McCullough. AB - The article by Baker and McCullough in this issue posits that bioethics has generally applied moral theories to practical problems. They propose that, rather than this "application," bioethicists should "appropriate" aspects of ethical theory. This article disagrees that bioethical writing is primary "application." It agrees that "appropriation" is the most suitable approach to bioethical analysis but claims that the description of appropriation provided by Baker and McCullough is inadequate. It must be supplemented by the rhetorical concept of "invention." PMID- 17849665 TI - Roles of moral philosophy in appropriated bioethics: a response to Baker and McCullough. AB - Strong arguments support the notion that much of modern bioethics is a result of appropriation rather than strict application of traditional moral philosophy. Nevertheless, it is important to recognize these sources and approaches associated with them, even when working with appropriated theories, since traditional ethical theory does and should influence modern bioethics. PMID- 17849664 TI - History and theory in "applied ethics". AB - Robert Baker and Laurence McCullough argue that the "applied ethics model" is deficient and in need of a replacement model. However, they supply no clear meaning to "applied ethics" and miss most of what is important in the literature on methodology that treats this question. The Baker-McCullough account of medical and applied ethics is a straw man that has had no influence in these fields or in philosophical ethics. The authors are also on shaky historical grounds in dealing with two problems: (1) the historical source of the notion of "practical ethics" and (2) the historical source of and the assimilation of the term "autonomy" into applied philosophy and professional ethics. They mistakenly hold (1) that the expression "practical ethics" was first used in a publication by Thomas Percival and (2) that Kant is the primary historical source of the notion of autonomy as that notion is used in contemporary applied ethics. PMID- 17849666 TI - Virginia Tech. PMID- 17849667 TI - Trivial and frivolous legislation and litigation--there ought to be a law. PMID- 17849668 TI - An analysis of the efficacy and safety of enhanced external counterpulsation at West Virginia University Hospitals. AB - A retrospective analysis was conducted of 79 consecutive patients who underwent enhanced external counterpulsation (EECP) at West Virginia University Hospitals during the period of November 1998 to September 2005 to determine its efficacy and safety in treating angina. A chart review and/or phone survey was performed to analyze pertinent clinical data (sublingual nitroglycerin use and angina class) pre and post EECP. A total of 60 (76%) patients who were referred for EECP successfully finished the 35 treatments. Seventy-five percent of the patient population improved at least one angina class after a full course of treatment. Therapy was discontinued due to adverse effects in 12 (15%) patients. Statistically significant improvements in angina class and reduction in anti angina medications were observed in every co-morbid subgroup analyzed, including patients with peripheral vascular disease, diabetes, hyperlipidemia, hypertension, smoking, Post-MI, and LVEF < 40% (P < .05, Wilcoxon Signed-Rank test). Overall, EECP was effective in improving angina as reflected in a substantial reduction in antiangina medications in 59 (75%) patients. PMID- 17849669 TI - Brain death: a challenging diagnosis in trauma patients. AB - Brain death is a catastrophic consequence of trauma, and diagnosing it can be a challenging for physicians because it presents in numerous ways. Since existing recommendations are not applicable to all hospitals because of the requirement of special equipment and highly-trained personnel, a committee of health care professionals at Charleston Area Medical Center in Charleston decided to review the available literature and create a new set of protocols regarding brain death. This article summarizes the findings of the committee and provides recommendations for physicians working with trauma patients. PMID- 17849670 TI - Aldosterone-secreting adrenal cortical carcinoma: a case report. AB - We present a case of aldosterone-secreting adrenal cortical carcinoma. The patient had an isolated elevation of aldosterone levels. This diagnosis should be suspected in patients first seen with hypertension and hypokalemia since this tumor may not always be considered in the differential diagnosis. PMID- 17849671 TI - Transperitoneal migration of multiple ova in a didelphic uterus: a case report. AB - Transperitioneal migration of the ova takes place frequently. This condition is often diagnosed during ectopic pregnancies. There are no case reports of such an occurrence in a multiple pregnancy with a didelphic uterus. PMID- 17849672 TI - It's time for a comprehensive interdisciplinary patient safety taxonomy. PMID- 17849673 TI - Pay for performance--neither necessary nor sufficient for quality improvement, yet vital for success. PMID- 17849674 TI - Making the Patient Safety and Quality Improvement Act of 2005 work. AB - Potential reasons for failure to report medical errors include concerns about adverse publicity, fear of litigation and professional sanctions, the burden of reporting, uncertainty about what information is required to be reported, and lack of feedback. The Patient Safety Quality and Improvement Act of 2005 (PSQIA) was passed by the U.S. Congress as a response to these issues. Successful implementation of PSQIA requires changes such as moving toward an incentive-based system or providing continuing education programs for healthcare providers. In addition, the reform of residency programs will help in the implementation of PSQIA by future healthcare providers. PMID- 17849675 TI - Simulation-based medical error disclosure training for pediatric healthcare professionals. AB - Ethical and regulatory guidelines recommend disclosure of medical errors to patients and families. Yet few studies examine how to effectively train healthcare professionals to deliver communications about adverse events to family members of affected pediatric patients. This pilot study uses a preintervention postintervention study design to investigate the effects of medical error disclosure training in a simulated setting for pediatric oncology nurses (N=16). The results of a paired t test showed statistically significant increases in nurses' communication self-efficacy to carry out medical disclosure (t = 6.68, p < .001). Ratings of setting "realism" and simulation effectiveness were high (21 out of 25 composite score). Findings provide preliminary support for further research on simulation-based disclosure training for healthcare professionals. PMID- 17849676 TI - Reliability and validity of hand hygiene measures. AB - Hand hygiene is undoubtedly the most important strategy in combating the increasing incidence and debilitating effects of multidrug-resistant organisms in healthcare. Research on effective approaches for increasing compliance with hand hygiene is imperative, but the first step is to identify how to reliably and validly measure hand hygiene. This article examines publications between the years 1990 and 2006 that address measures of hand hygiene. The findings indicate that further research is needed to identify reliable and valid measures of hand hygiene. PMID- 17849677 TI - E. Scott Geller on people-based healthcare safety. Interview by Susan V White. PMID- 17849678 TI - Tania Daniels on the Minnesota Alliance for Patient Safety. Interview by Susan V White. PMID- 17849679 TI - Medication reconciliation: Harvard Pilgrim Health Care's approach to improving outpatient medication safety. AB - Hospitals and long-term care facilities have been addressing the issue of patient safety for some time. As a result of the increasing number of outpatient medication errors leading to adverse drug events (ADEs), interest in preventing outpatient medication errors has increased. Research indicates that the rate of outpatient ADEs may be about four times as high as that reported in hospital studies and that more than one third of these events are preventable (Gandhi et al., 2003). Harvard Pilgrim Health Care introduced its Medication Reconciliation Program in an effort to enhance patient safety by improving medication use and safety. PMID- 17849680 TI - Evaluating initiatives to reduce seclusion and restraint. AB - The use of institutional measures of control such as seclusion and restraint within psychiatric hospitals is common and arguably countertherapeutic; however, little is known about how best to reduce the use of these measures. The development and implementation of new institutional strategies to reduce the use of seclusion and restraint are important. Although traditional performance improvement (PI) project methodology might seem well-suited to helping managers and administrators identify effective hospital-wide interventions to decrease seclusion and restraint rates, the Logic of the standard PI model precludes managers from making valid inferences about which interventions actually cause change. This article presents a model (derivative of the multiple baseline time series design with randomization) for testing individual elements of a Large scale PI project to reduce the use of seclusion and restraint in a behavioral healthcare organization. The proposed model is flexible, accommodates overlapping organizational initiatives, and simultaneously allows for meaningful inferences to be made about the active components of the interventions. The ability to make meaningful inferences is important because, if the initiatives to reduce seclusion and restraint rates work, other healthcare organizations would benefit from knowing Key Words which specific interventions actually Lead engagement model to change and which interventions have multiple baseline design Little impact on secLusion and restraint performance improvement rates. Early experiences with this model psychiatry from a hospital manager's perspective sanctuary trauma are discussed, along with the costs and benefits of using it. PMID- 17849681 TI - Determinants of oral health behaviour among Iranian dentists. AB - AIM: To study the oral health behaviour of Iranian dentists. DESIGN: A cross sectional study. SETTING: Two annual dental meetings in Tehran, Iran. PARTICIPANTS: 1,033 dentists responded, 980 were eligible for this study. METHOD: Data were collected using a self-administered questionnaire which covered dentists' oral self-care, dental attendance, and smoking. Recommended oral self care (ROSC) included tooth brushing > 1/day, eating sugary snacks < daily, and regularly using fluoride toothpaste. Knowledge of preventive dental care was assessed by nine Likert-scale statements. Dentist's gender, age, and professional reading were recorded. Statistical evaluation was by the Chi-square test and logistic regression. RESULTS: In total, 59% of respondents reported brushing their teeth at least 2/day, 59% consumed sugary snacks < daily, 74% used fluoride toothpaste regularly, and 76% were non-smokers. Of all, 27% followed ROSC. Women reported desirable behaviours more frequently than did the men (p < 0.01). Female gender (OR 1.4-2.3), being a non-smoker (OR 1.3-1.5), and wider professional reading (OR = 1.2) were the major factors that contributed to dentists' desirable oral health behaviour. CONCLUSIONS: That only a small number of Iranian dentists follow the ROSC calls for more attention to behavioural contributions to oral diseases and its consequences with general and oral health, regarding both dental curriculum and continuing education. PMID- 17849682 TI - Effects of dentifrices on artificial caries like lesions: an in vitro pH cycling study. AB - AIM: To evaluate remineralising effects of three dentifrices, Vicco by Vicco Labs, India, Perioe Cavity Care by LG Care, Korea and Colgate Total by Colgate Palmolive, Thailand on artificial caries like lesions. DESIGN: In vitro single section and pH cycling model. METHODS: Extracted third molars were painted with nail varnish, leaving 1 mm wide windows before placing demineralising solution for 96h to produce artificial carious lesions 150-200 miocrom deep. Teeth were then cut longitudinally into 100-150 microm thick sections and randomly assigned to three groups. Polarised light microscopy and microradiography were used to evaluate lesion depth, before and after the 10 day pH cycle. Sections in Group A were treated with Vicco by Vicco Labs, India (-ve control), Group B were treated with Perioe Cavity Care by LG Care, Korea and Group C were treated with Colgate Total by Colgate-Palmolive, Thailand. RESULTS: Mean lesion depths in Groups B and C reduced by 7% and 12% respectively, whereas lesion depth increased by 13% in Group A. Comparisons made among groups using ANOVA and Student-Newman-Keuls tests showed that three groups were significantly different from each other (p < 0.05). CONCLUSIONS: Perioe Cavity Care and Colgate Total remineralised initial carious lesions. However, the remineralising potential of Colgate Total was higher than that of Perioe Cavity Care. PMID- 17849683 TI - Oral aspects of obesity. AB - Obesity (Body Mass Index > or = 30 kg/m2) has a high prevalence of 15-30% among European and American populations. It is an incurable chronic disease with a considerable mortality and co-morbidity. The co-morbidity can be reduced substantially by a moderate weight loss of 5-15%. The main cause of obesity is an imbalance between energy intake and energy expenditure. Therefore, the treatment starts with an energy restricted diet, a reduction of sedentary lifestyle, increased physical activity, and behavioural therapy to change eating habits. When necessary, this treatment can be followed by pharmacotherapy or surgery. Obesity is related to several aspects of oral health, such as caries, periodontitis and xerostomia. In addition, obesity may have implications for the dental treatment plan. PMID- 17849684 TI - Preterm low birth weights associated with periodontal disease in the Fiji Islands. AB - AIM: To determine any association between pre-term low birth weight (PTLBW) neonates and periodontal disease during the mother's pregnancy. DESIGN: A multi centered prospective case cohort study. SETTING: Ante-natal clinics at the Colonial War Memorial and Lautoka Hospitals, Fiji from 1st January to 30th June 2004. PARTICIPANTS: 670 multiethnic pregnant women. METHODS: Participants were interviewed to identify confounding variables--medical conditions, smoking, alcohol consumption, maternal age and history of preterm birth. Oral examination was conducted and included the Community Periodontal Index of Treatment Needs (CPITN). Delivery outcome was recorded for each woman. RESULTS: The mean age of participants was 25.80 +/- 5.56 years. 1.9% (n=13) women delivered preterm babies. More than 50% of this group displayed moderate to severe periodontitis compared with 13% of women who had a normal delivery. Preterm birth was also associated with the mother having had a previous preterm birth and who was more likely to be Indo-Fijian (p < 0.01). There was no significant association with where the mother lived; however, rural women with PTLBW babies had more severe periodontal disease (p = 0.0001). CONCLUSION: There is a highly significant association between pre-term birth and moderate to severe periodontal disease (p = 0.0001). PMID- 17849685 TI - Future project concerning mass disaster management: a forensic odontology prospectus. AB - The world has experienced a plethora of mass disasters in recent years: acts of terrorism, bombings, earthquakes, hurricanes, typhoons, air crashes and other transportation mishaps, not to mention armed conflicts and migrants drowned in the Mediterranean Sea. In reviewing mass disasters to date, the principal difficulties have not changed: (1) large numbers of humans fragmented, co mingled, and burned remains; (2) difficulty in determining who was involved in the disaster; (3) acquisition of useful medical and dental records and radiographs; (4) legal, jurisdictional, organisational, and political issues; (5) internal and external documentation and communication problems; (6) application of universal human forensic identification codes. Forensic dentistry plays a major role in victim identification. DNA and dental identification of human remains depends on sufficient availability of ante mortem information, existence of sufficient post mortem material and a comparison or match between ante and post mortem details. Forensic odontology is a specialty with a specific training, and cannot simply be carried out by dentists without such training. Strategies for developing an international forensic odontology capacity and resources are needed for the management of dead bodies following a mass disaster, together with universal guidelines and codes. To this end, Interpol's forms have proved to be a good starting point to meet these requirements. PMID- 17849686 TI - Utilisation of dental auxiliaries--attitudinal review from six developed countries. AB - OBJECTIVE: To identify reasons for the development of dental auxiliaries across six developed countries and to explore attitudes towards them. DESIGN: Literature review; semistructured interviews with key informants. SETTING: Interviews in each selected country; Belgium, Greece, Finland, U.K., Canada and New Zealand. MATERIALS AND METHODS: For each country, representatives of key informants were interviewed. RESULTS: The introduction of dental auxiliaries in many countries was as a result of workforce shortages. There has been no development of dental auxiliaries in Belgium or Greece largely because of perceived lack of need by the representative respondents. In Canada, Finland, New Zealand and the U.K. the introduction of clinical dental auxiliaries was a result of shortages of workforce and high levels of disease. Concerns amongst dentists were about the pace of the increased scope of practice for auxiliaries and by auxiliaries about lack of career development. CONCLUSIONS: Two distinct professional attitudes towards dental auxiliaries were found--in Belgium and Greece, there is little or no support compared with the other countries, where, in general, professional attitudes support the use of dental hygienists but are less supportive of therapists and denturists. PMID- 17849687 TI - Education of dentists in Thailand. AB - Thailand is geographically located in southeast Asia and its population is 63 million. Little has been published on dental education in Thailand. This paper provides information about Thailand regarding its dental history, dental school system including curriculum and dental licensure. There are eight public and one private dental school in Thailand. A six-year dental education leads to the DDS degree. On graduation from the public dental schools, dentists are required to work in the public system for three years. Currently, there are approximately 8000 active dentists, with a dentist: population ratio of approximately 1:7000. PMID- 17849688 TI - Outcome of career expectancies and early professional burnout among newly qualified dentists. AB - OBJECTIVES: To measure burnout development, outcome of expectations with regard to dental career and feelings of being unprepared for practice among newly graduated general dental practitioners. METHODS: In 1997, 50 dentists were approached to fill in the Maslach Burnout Inventory, Dutch version (UBOS) and some additional variables between six months and one year after graduation at the Academic Centre for Dentistry Amsterdam (ACTA) (76% response). Six years later, in 2003, the same 50 dentists, plus another 60 who had graduated in the same period at ACTA, were approached (78% response). RESULTS: Using Repeated Measures analysis, mean scores of dentists for whom two measurements were available on the three UBOS subscales (N=24) showed no statistically significant changes over six years on Emotional Exhaustion, Depersonalisation, or Personal Accomplishment. The same was true for group means of all in 1997 (N=33) compared with all in 2003 (N=82). However, according to manual criteria, varying percentages (7.2% - 24.4%) of dentists showed an unfavourable level on either one of the UBOS dimensions. Factors most frequently mentioned to be responsible for being unprepared for practice were: law and insurance matters (61.2%), practice organisation (56.6%) and staff management (55.2%). Most frequently reported factors that came out (much) worse than expected were: stressfulness of work (45.1%), and staff management (43.4%). CONCLUSIONS: Burnout appears no threat for the average newly qualified dentist. However, some individuals report alarmingly high burnout scores at an early professional stage. Practice management is the professional aspect about which young professionals worry most. It is recommended that dental schools pay attention to practice management skills and the stressfulness of work in the curriculum. Also, longitudinal monitoring of dental students and newly qualified dentists on burnout development is strongly advocated. PMID- 17849689 TI - Subcutaneous cervical emphysema induced by a dental air syringe: a case report. AB - Subcutaneous emphysema is one potential complication of dental procedures, although most cases of emphysema implicate operative procedure. We present a rare case of subcutaneous emphysema which arose due to using an air syringe to dry the gingiva in the lower jaw. PMID- 17849690 TI - The kidney in the critically ill. AB - Acute kidney injury (AKI) is a common and serious complication in the intensive care setting. It seldom occurs in isolation, but is mostly part of a multiple organ dysfunction syndrome. The pathogenesis is frequently multifactorial, with sepsis contributing to 50% of the cases.The development of AKI in critically-ill patients is "bad news": patients with AKI have a high morbidity and mortality. In addition, AKI, even in its mildest from, is not only a marker of illness severity but appears to be independently associated with mortality. Prevention of AKI is therefore a major goal to improve outcome of critically-ill patients. Treatment of established AKI is largely supportive. The optimal modality for renal replacement therapy in critically-ill patients still remains a matter of debate). The majority of survivors recover renal function. PMID- 17849691 TI - Kidney transplantation: current issues and future prospects. PMID- 17849692 TI - The effect of infliximab treatment on insulin resistance in patients with rheumatoid arthritis. AB - AIM: It is well known that increased insulin resistance is associated with the development of cardiovascular disease in patients with rheumatoid arthritis and that tumour necrosis factor-alpha plays an important role in this process. Infliximab is a chimeric monoclonal anti-tumour necrosis factor-alpha antibody. This study investigates the effects of long term infliximab treatment on insulin resistance in patients with rheumatoid arthritis. MATERIALS AND METHODS: Seven rheumatoid arthritis patients (6 female and 1 male; mean age: 44.6 +/- 12.3, mean duration of disease: 6.8 y) for whom infliximab treatment had been planned at the rheumatology and internal medicine clinics were included. Patients were evaluated during and at the end of the study with a mean follow-up duration of 9.6 months. Fasting plasma glucose, fasting plasma insulin levels and serum lipid profile were assessed at baseline and throughout the treatment period (prior to every infusion). Homeostasis Model Assessment of Insulin Resistance model was used for the assessment of insulin sensitivity. RESULTS: Fasting insulin and Homeostasis Mode Assessment of Insulin Resistance levels decreased after treatment (from 19.4 +/- 7.7 microU/ml to 8.9 +/- 4.1 microU/ml and from 2.4 +/- 1 to 1.1 +/- 0.5, respectively; p < 0.05 for both). No significant change was observed in other parameters. CONCLUSION: An improvement in insulin sensitivity was observed in patients receiving long term infliximab treatment for rheumatoid arthritis. PMID- 17849694 TI - The diabetic foot: established and emerging treatments. AB - The diabetic foot is a major cause of morbidity and mortality. The present review aims to outline current treatment options for this ghastly diabetic complication. Although considerable progress has been achieved over the past years, there is still a long way to go. Indeed, the International Working Group of the Diabetic Foot reported 2 years ago that a lower extremity was amputated every 30 seconds due to diabetes somewhere in the world. Established therapeutic modalities (revascularisation, casting and debridement) remain the cornerstone of management. At the same time, new treatments (e.g. growth factors, bioengineered skin substitutes, extracellular matrix proteins, etc.) are continuously being developed and explored to improve treatment. Nonetheless, it should not be underestimated that both new and old treatments must be incorporated in a prudent and zealous therapeutic strategy. Essentially, only multidisciplinary foot clinics have demonstrated that the reduction of amputation rates is feasible. The endeavour should be coupled with widespread education on the elementary rules to achieve both primary and secondary prevention. PMID- 17849693 TI - A Belgian registry of interleukin-2 administration for treatment of metastatic renal cell cancer and confrontation with literature data. AB - In an effort to map the use of interleukin-2 (IL-2) treatment in patients with clear cell renal cell cancer (RCC) in Belgian hospitals, 44 cases were registered from 9 hospitals between February 2003 and June 2006. It was demonstrated that the majority of these patients were treated with subcutaneous (SC) IL-2. Other methods such as the inhalation of the drug in case of intrathoracic disease or high dose intravenous (IV) administration were much less frequent (3 and 0 cases in this registry, respectively). The results of antitumour activity (around 16% partial response-absence of complete responses) and toxicity of this drug correlate with observations from the literature with the SC administration. In view of the poor results and tolerance with the currently used cytokines (IL-2 or interferon-alfa), much hope is directed towards the development of the novel targeted drugs like sunitinib or sorafenib used alone or in combination with cytokines in this disease. PMID- 17849695 TI - Extensive emphysematous pyelonephritis. AB - We report an unusually severe case of emphysematous pyelonephritis with very extensive kidney necrosis that led to unilateral nephrectomy. We discuss the diagnosis and treatment options in this very rare complication of pyelonephritis almost exclusively encoutered in diabetic patients. PMID- 17849696 TI - Bilateral adrenal masses as the sole clinical key for diagnosing a Histoplasma capsulatum infection. AB - We describe a case of a 52-year-old man presenting with bilateral adrenal masses. A Histoplasma capsulatum infection was diagnosed on the basis of culture, pathological findings, Histoplasma antigen detection and molecular testing. The patient was treated with itraconazole and initially showed a good response. However, after discontinuation of one year of therapy, a relapse was seen and therapy was restarted. This case illustrates that histoplasmosis should be considered in the differential diagnosis of patients presenting with bilateral adrenal enlargement. Of all the diagnostic tests that are available, serology and antigen detection are the only rapid and non-invasive tests. Antigen detection can also be used for further follow-up of the disease. PMID- 17849697 TI - The cat conundrum. PMID- 17849698 TI - Hot on the trail of the rabies cure. PMID- 17849699 TI - Clinical snapshot. Biliary adenoma. PMID- 17849700 TI - Gastroenteropathy in Norwegian Lundehunds. AB - Norwegian Lundehunds are often affected by gastrointestinal disease, the most common clinical signs of which are intermittent diarrhea, vomiting, weight loss, lethargy, ascites, and subcutaneous edema of the hind legs. The most frequent laboratory changes include hypoalbuminemia (with or without hypoglobulinemia), hypocalcemia, a decrease in the serum cobalamin concentration, and an increase or decrease in the serum folate concentration, reflecting microbial synthesis or malabsorption, respectively. Histopathologic abnormalities can include chronic atrophic gastritis, intestinal lymphangiectasia, and lymphoplasmacytic enteritis. Because the underlying cause of gastroenteropathy in Norwegian Lundehunds has not been identified, treatment is symptomatic. PMID- 17849701 TI - The use of thrombolytic agents. AB - Thrombi and thromboemboli are organized fibrin clots that may result in partial or total occlusion of arterial or venous blood flow. Consequences of occlusion of blood flow vary with the organ affected.Thrombolytic agents have been used for the dissolution of pathologic thrombi since the 1980s. While similar in their mechanisms of action and side effects, these agents differ in their specificity for fibrin and duration of activity. Newer thrombolytic agents have been developed to improve clot dissolution and minimize side effects. Their use in veterinary medicine has been reported, but guidelines for such use have not been published. PMID- 17849702 TI - Human feet are not mice: how to treat human-directed feline aggression. PMID- 17849703 TI - Noninfectious inflammatory central nervous system diseases in dogs. AB - Inflammatory diseases of the central nervous system are often challenging to diagnose. Necrotizing meningoencephalitis, necrotizing leukoencephalitis, and granulomatous meningoencephalomyelitis have characteristic locations of lesions on histopathologic examination and, therefore, characteristic findings from advanced imaging. Together with clinical signs and clinicopathologic data, these characteristic imaging findings may aid in establishing an accurate antemortem diagnosis. Prompt diagnosis can lead to initiation of treatment using a combination of immunosuppressive drugs. PMID- 17849704 TI - Check-in procedures for plant cell entry by biotrophic microbes. AB - Significant advances in the cell biology of plant-microbe interactions have been achieved recently, to a large extent based on new technical approaches such as the use of fluorescent protein tags in model plants exploited in conjunction with available genetic resources. They have highlighted the pivotal role played by epidermal cells as the first site at which direct cell-to-cell contact takes place between the plant and microbes it may host. Here, we compare the cellular aspects of early biotrophic interactions with symbiotic and pathogenic microbes and evaluate the hypothesis that their hosting by plant cells share common traits related to the necessity of preserving host-cell integrity. The cellular events that accompany cell entry by the different biotrophs are divided into three categories, depending on whether the cellular changes are triggered by diffusible molecules, direct contact, or cell lumen penetration. Similarities and differences mirror the nutritional and developmental strategies of each plant interacting organism, underlining the fact that plant cell entry represents a key aspect in the establishment of biotrophy. PMID- 17849705 TI - Pattern recognition receptors: from the cell surface to intracellular dynamics. AB - Detection of potentially infectious microorganisms is essential for plant immunity. Microbial communities growing on plant surfaces are constantly monitored according to their conserved microbe-associated molecular patterns (MAMPs). In recent years, several pattern-recognition receptors, including receptor-like kinases and receptor-like proteins, and their contribution to disease resistance have been described. MAMP signaling must be carefully controlled and seems to involve receptor endocytosis. As a further surveillance layer, plants are able to specifically recognize microbial effector molecules via nucleotide-binding site leucine-rich repeat receptors (NB-LRR). A number of recent studies show that NB-LRR translocate to the nucleus in order to exert their activity. In this review, current knowledge regarding the recognition of MAMPs by surface receptors, receptor activation, signaling, and subcellular redistribution are discussed. PMID- 17849706 TI - Nodulation studies in the model legume Medicago truncatula: advantages of using the constitutive EF1alpha promoter and limitations in detecting fluorescent reporter proteins in nodule tissues. AB - The Cauliflower mosaic virus 35S promoter currently is being used in RNAi-based approaches for attenuating host gene expression during legume root nodule development and also for the expression of fluorescent reporters in nodule tissues. In this study, we have evaluated the expression of this promoter in the indeterminate nodules of the model plant Medicago truncatula. Our results clearly show that the 35S promoter is inactive in both the nodule meristem and in bacteroid-containing cells of the nodules. On the other hand, the Arabidopsis thaliana EF1alpha promoter was found to be strongly expressed both in the nodule meristem and in all nodule-invaded cells. Therefore, we conclude that the constitutive EF1alpha promoter is far superior for mRNAi or overexpression studies in nodule tissues compared with the commonly used 35S promoter. In addition, our experiments have revealed that the intensity of fluorescent markers such as green fluorescent protein is severely attenuated within invaded cells in the nitrogen-fixation zone of the nodule, most likely by fluorescence quenching. This phenomenon may hinder the use of these tools for live-cell imaging in nodule tissue. PMID- 17849707 TI - Inhibition of Agrobacterium-induced cell death by antiapoptotic gene expression leads to very high transformation efficiency of banana. AB - The death of plant cells in culture following exposure to Agrobacterium tumefaciens remains a major obstacle in developing Agrobacterium-mediated transformation into a highly efficient genotype-independent technology. Here, we present evidence that A. tumefaciens exposure induces cell death in banana cell suspensions. More than 90% of embryogenic banana cells died after exposure to A. tumefaciens and cell death was accompanied by a subset of features associated with apoptosis in mammalian cells, including DNA laddering, fragmentation, and formation of apoptotic-like bodies. Importantly, these cellular responses were inhibited in cells expressing the animal antiapoptosis genes Bcl-xL, Bcl-2 3' untranslated region, and CED-9. Inhibition of cell death resulted in up to 90% of cell clumps transformed with Bcl-xL, a 100-fold enhancement over vector controls, approaching the transformation and regeneration of every "transformable" cell. Similar results using sugarcane, a crop plant known for recalcitrance to Agrobacterium transformation, suggest that antiapoptosis genes may inhibit these phenomena and increase the transformation frequency of many recalcitrant plant species, including the major monocot cereal crop plants. Evidence of inhibition of plant cell death by cross-kingdom antiapoptotic genes also contributes to the growing evidence that genes for control of programmed cell death are conserved across wide evolutionary distances, even though these mechanisms are not well understood in plants. PMID- 17849708 TI - Laser microdissection reveals that transcripts for five plant and one fungal phosphate transporter genes are contemporaneously present in arbusculated cells. AB - The establishment of a symbiotic interaction between plant roots and arbuscular mycorrhizal (AM) fungi requires both partners to undergo significant morphological and physiological modifications which eventually lead to reciprocal beneficial effects. Extensive changes in gene expression profiles recently have been described in transcriptomic studies that have analyzed the whole mycorrhizal root. However, because root colonization by AM fungi involves different cell types, a cell-specific gene expression pattern is likely to occur. We have applied the laser microdissection (LMD) technology to investigate expression profiles of both plant and fungal genes in Lycopersicon esculentum roots colonized by Glomus mosseae. A protocol to harvest arbuscule-containing cells from paraffin sections of mycorrhizal roots has been developed using a Leica AS LMD system. RNA of satisfactory quantity and quality has been extracted for molecular analysis. Transcripts for plant phosphate transporters (LePTs), selected as molecular markers for a functional symbiosis, have been detected by reverse-transcriptase polymerase chain reaction assays and associated to distinct cell types, leading to novel insights into the distribution of LePT mRNAs. In fact, the transcripts of the five phosphate transporters (PTs) have been detected contemporaneously in the same arbusculated cell population, unlike from the neighboring noncolonized cells. In addition, fungal H(+)ATPase (GmHA5) and phosphate transporter (GmosPT) mRNAs were found exclusively in arbusculated cells. The discovery that five plant and one fungal PT genes are consistently expressed inside the arbusculated cells provides a new scenario for plant-fungus nutrient exchanges. PMID- 17849709 TI - Characterization of the nonconserved hpaB-hrpF region in the hrp pathogenicity island from Xanthomonas campestris pv. vesicatoria. AB - The interaction of the gram-negative phytopathogenic bacterium Xanthomonas campestris pv. vesicatoria with its host plants pepper and tomato is mediated by a type III secretion (T3S) system that translocates bacterial effector proteins into the plant cell. The T3S system is encoded by the chromosomal hrp (hypersensitive response and pathogenicity) gene cluster. Here, we report on the analysis of the hpaB-hrpF region, which encodes the novel virulence factor HpaE, the effector protein XopF1, and two proteins with unknown functions, HpaD and HpaI. Promoter and transcript analyses revealed that the corresponding genes are coexpressed with the hrp genes and that hpaD, hpaI, and xopF1 form a novel operon. In vitro and in vivo assays showed that the efficient T3S and translocation of XopF1 depends on the global T3S chaperone HpaB and the putative lytic transglycosylase HpaH, which specifically contributes to the secretion of a certain set of effectors. Taken together, our data suggest that the efficient secretion of effector proteins in X. campestris pv. vesicatoria requires the contribution of several different Hpa proteins. PMID- 17849710 TI - The same allele of translation initiation factor 4E mediates resistance against two Potyvirus spp. in Pisum sativum. AB - Pathogenicity of two sequenced isolates of Bean yellow mosaic virus (BYMV) was established on genotypes of Pisum sativum L. reported to carry resistance genes to BYMV and other potyviruses. Resistance to the white lupin strain of BYMV (BYMV W) is inherited as a recessive gene named wlv that maps to linkage group VI together with other Potyvirus resistances. One of these, sbm1, confers resistance to strains of Pea seedborne mosaic virus and previously has been identified as a mutant allele of the eukaryotic translation initiation factor 4E gene (eIF4E). Sequence comparison of eIF4E from BYMV-W-susceptible and -resistant P. sativum genotypes revealed a polymorphism correlating with the resistance profile. Expression of eIF4E from susceptible plants in resistant plants facilitated BYMV W infection in inoculated leaves. When cDNA of BYMV-W was agroinoculated, resistance mediated by the wlv gene frequently was overcome, and virus from these plants had a codon change causing an Arg to His change at position 116 of the predicted viral genome-linked protein (VPg). Accordingly, plants carrying the wlv resistance gene were infected upon inoculation with BYMV-W derived from cDNA with a His codon at position 116 of the VPg coding region. These results suggested that VPg determined pathogenicity on plants carrying the wlv resistance gene and that wlv corresponded to the sbm1 allele of eIF4E. PMID- 17849711 TI - The role of cellulose and O-antigen capsule in the colonization of plants by Salmonella enterica. AB - Numerous salmonellosis outbreaks have been associated with vegetables, in particular sprouted seed. Thin aggregative fimbriae (Tafi), a component of the extracellular matrix responsible for multicellular behavior, are important for Salmonella enterica attachment and colonization of plants. Here, we demonstrate that the other surface polymers composing the extracellular matrix, cellulose, and O-antigen capsule also play a role in colonization of plants. Mutations in bacterial cellulose synthesis (bcsA) and O-antigen capsule assembly and translocation (yihO) reduced the ability to attach to and colonize alfalfa sprouts. A colanic acid mutant was unaffected in plant attachment or colonization. Tafi, cellulose synthesis, and O-antigen capsule, all of which contribute to attachment and colonization of plants, are regulated by AgfD, suggesting that AgfD is a key regulator for survival outside of hosts of Salmonella spp. The cellulose biosynthesis regulator adrA mutant was not affected in the ability to attach to or colonize plants; however, promoter probe assays revealed expression by cells attached to alfalfa sprouts. Furthermore, quantitative reverse-transcriptase polymerase chain reaction revealed differential expression of agfD and adrA between planktonic and plant-attached cells. In addition, there was no correlation among mutants between biofilm formation in culture and attachment to plants. Outside of animal hosts, S. enterica appears to rely on an arsenal of adhesins to persist on plants, which can act as vectors and perpetuate public health concerns. PMID- 17849712 TI - The chitin-binding Cladosporium fulvum effector protein Avr4 is a virulence factor. AB - The biotrophic fungal pathogen Cladosporium fulvum (syn. Passalora fulva) is the causal agent of tomato leaf mold. The Avr4 protein belongs to a set of effectors that is secreted by C. fulvum during infection and is thought to play a role in pathogen virulence. Previous studies have shown that Avr4 binds to chitin present in fungal cell walls and that, through this binding, Avr4 can protect these cell walls against hydrolysis by plant chitinases. In this study, we demonstrate that Avr4 expression in Arabidopsis results in increased virulence of several fungal pathogens with exposed chitin in their cell walls, whereas the virulence of a bacterium and an oomycete remained unaltered. Heterologous expression of Avr4 in tomato increased the virulence of Fusarium oxysporum f. sp. lycopersici. Through tomato GeneChip analyses, we demonstrate that Avr4 expression in tomato results in the induced expression of only a few genes. Finally, we demonstrate that silencing of the Avr4 gene in C. fulvum decreases its virulence on tomato. This is the first report on the intrinsic function of a fungal avirulence protein that has a counter-defensive activity required for full virulence of the pathogen. PMID- 17849713 TI - GcSTUA, an APSES transcription factor, is required for generation of appressorial turgor pressure and full pathogenicity of Glomerella cingulata. AB - Glomerella cingulata, which infects a number of different hosts, gains entry to the plant tissue by means of an appressorium. Turgor pressure generated within the appressorium forces a penetration peg through the plant cuticle. A visible lesion forms as the fungus continues to grow within the host. A G. cingulata homolog (GcSTUA) of the genes encoding Asm1, Phd1, Sok2, Efg1, and StuA transcription factors in Magnaporthe grisea and other fungi was cloned and shown to be required for infection of intact apple fruit and penetration of onion epidermal cells. Mobilization of glycogen and triacylglycerol during formation of appressoria by the GcSTUA deletion mutant appeared normal and melanization of the maturing appressoria was also indistinguishable from that of the wild type. However, GcSTUA was essential for the generation of normal turgor pressure within the appressorium. As is the case for its homologs in other fungi, GcSTUA also was required for the formation of aerial hyphae, efficient conidiation, and the formation of perithecia (sexual reproductive structures). PMID- 17849714 TI - Induction of a grapevine germin-like protein (VvGLP3) gene is closely linked to the site of Erysiphe necator infection: a possible role in defense? AB - Germin-like proteins (GLP) have various proposed roles in plant development and defense. Seven novel GLP cDNA clones were isolated from grapevine (Vitis vinifera cv. Chardonnay). Reverse transcriptase-polymerase chain reaction expression analysis revealed that the VvGLP genes exhibit diverse and highly specific patterns of expression in response to a variety of abiotic and biotic treatments, including challenge by Erysiphe necator, Plasmopara viticola, and Botrytis cinerea, suggesting a diversity of roles for each of the GLP family members. Significantly, one of the grapevine GLP genes, VvGLP3, is induced specifically by E. necator infection and expression is closely linked to the site of infection. Subcellular localization of VvGLP3 determined by transient expression of a VvGLP3:GFP fusion construct in onion cells indicated that the recombinant protein was targeted to the cell wall. Recombinant VvGLP3 was successfully expressed in Arabidopsis thaliana and the partially purified recombinant protein was demonstrated to have superoxide dismutase activity. This data has provided an insight into the diverse nature of the GLP family in grapevine and suggests that VvGLP3 may be involved in the defense response against E. necator. PMID- 17849715 TI - Elevated genetic variation within virulence-associated Botrytis cinerea polygalacturonase loci. AB - Botrytis cinerea, or gray mold, is a necrotrophic fungal pathogen of hundreds of plant species. The genetic diversity of B. cinerea may contribute to its broad host range; however, the level and structure of genetic variation at pathogenesis associated loci has not been described. B. cinerea possesses six distinct cell wall-degrading polygalacturonases (PGs), enzymes of demonstrated importance to pathogenesis and interaction with host plant defenses. Sequencing a collection of 34 B. cinerea isolates at three PG-encoding loci, BcPG1, BcPG2, and BcPG3, revealed limited evidence of host-mediated genetic subdivision within loci, yet suggested differences in the action of evolutionary forces among loci. BcPG1 and BcPG2 are highly polymorphic, particularly when compared with previously published data from nonpathogenicity loci, whereas BcPG3 is relatively conserved. Sequence variation at BcPG1 and BcPG2 did not appear to be associated with virulence on Arabidopsis leaves; however, BcPG2 variation showed a statistically significant association with growth rate on pectin. Rather than providing evidence for host-mediated genetic subdivision at individual PG loci, our data support specialization among PGs and the potential diversification of PGs interacting directly with host defenses. PMID- 17849717 TI - The Colletotrichum acutatum gene encoding a putative pH-responsive transcription regulator is a key virulence determinant during fungal pathogenesis on citrus. AB - Postbloom fruit drop of citrus and Key lime anthracnose (KLA) are caused by different pathotypes of Colletotrichum acutatum. Both pathotypes are pathogenic to citrus flowers, resulting in blossom blight and induction of young fruit abscission. Two fungal mutants defective in pathogenicity were recovered from a KLA pathotype after Agrobacterium-mediated mutagenesis. A PacC(KLAP2) gene encoding a polypeptide that resembles many pH-responsive PacC/ Rim101 transcription regulators in fungi was identified from one of the mutants, and functionally characterized to play a crucial role in pathogenesis to both Key lime leaves and citrus flowers. Gene disruption at the Pac(KLAP2) locus created fungal mutants that were hypersensitive to alkaline pH, altered in conidium and appressorium production and germination, and concomitant with reduced virulence to both tissues. The pacC(KLAP2) null mutants had lower alkaline phosphatase and protease activities, but increased pectolytic and lipolytic activities. The mutants initiated penetration and incited lesion formation on Key lime, indistinguishable from the wild type, when a functional copy of PacC(KLAP2) was reintroduced or the leaves were wounded prior to inoculation. The null mutants were blocked at the penetration stage and, thus, failed to initiate the necrotrophic phase. The PacC(KLAP2) transcript was barely detectable when the fungus was grown on medium buffered to pH 3 or 4, yet accumulated to high levels at a pH between 5 and 7. The Pac(KLAP2) transcript was detected 2 days postinoculation on Key lime leaves, correlating with the time of lesion formation. We conclude that PacC(KLAP2) is essential for C. acutatum pathogenesis by regulating multiple physiological and developmental processes. PMID- 17849718 TI - Biochemical and molecular mechanisms involved in monogenic resistance responses to tomato powdery mildew. AB - The monogenic genes Ol-1, ol-2, and Ol-4 confer resistance to tomato powdery mildew Oidium neolycopersici via different mechanisms. The biochemical mechanisms involved in these monogenic resistances were studied by monitoring through time the association of H2O2 and callose accumulation with hypersensitive response (HR) and papilla formation. Our results showed that H2O2 and callose accumulation are coupled with both Ol-1- and Ol-4-mediated HR-associated resistance as well as with the ol-2-mediated papillae-associated resistance. Further, the transcriptomal changes related to these monogenic resistances were studied by using cDNA-amplification fragment length polymorphism. The expression profiling clarified that 81% of DE-TDF (differentially expressed transcript-derived fragments) were up-regulated upon inoculation with O. neolycopersici in both the compatible and Ol-1-mediated incompatible interactions, though with a difference in expression timing. Of these DE-TDF, more than 70% were not detected in the Ol 4-mediated resistance, while 58% were expressed in the ol-2-mediated resistance, generally at later timepoints. Sequence information suggested that most of these DE-TDF are related to genes involved in either basal defense or establishment of compatibility. In addition, DE-TDF (19%) specifically expressed in different incompatible interactions were identified. Expression patterns of some DE-TDF and marker gene GluB suggested that papillae-associated resistance exploits a different defense pathway from that of HR-associated resistance. PMID- 17849716 TI - Genomic organization and evolutionary insights on GRP and NCR genes, two large nodule-specific gene families in Medicago truncatula. AB - Deciphering the mechanisms leading to symbiotic nitrogen-fixing root nodule organogenesis in legumes resulted in the identification of numerous nodule specific genes and gene families. Among them, NCR and GRP genes encode short secreted peptides with potential antimicrobial activity. These genes appear to form large multigenic families in Medicago truncatula and other closely related legume species, whereas no similar genes were found in databases of Lotus japonicus and Glycine max. We analyzed the genomic organization of these genes as well as their evolutionary dynamics in the M. truncatula genome. A total of 108 NCR and 23 GRP genes have been mapped that were often clustered in the genome. These included 29 new NCR and 17 new GRP genes. Reverse transcription-polymerase chain reaction analyses of the novel genes confirmed their exclusive nodule specific expression similar to the previously identified members. Protein alignments and phylogenetic analyses revealed traces of several duplication events in the history of GRP and NCR genes. Moreover, microsyntenic evidences between M. truncatula and L. japonicus validated the hypothesis that these genes are specific for the inverted repeat-lacking clade of hologalegoid legumes, which allowed dating the appearance of these two gene families during the evolution of legume plants. PMID- 17849719 TI - As reimbursement shifts, efficient patient throughput becomes critical. PMID- 17849720 TI - CMs' role in patient throughput initiatives. PMID- 17849721 TI - Dry-erase board improves communication, discharge. PMID- 17849722 TI - Persistence pays off when placing difficult patients. PMID- 17849723 TI - CMs take lead in discharge improvement initiatives. PMID- 17849724 TI - Reduce your hospital's preventable readmissions. PMID- 17849725 TI - Respiratory section added to Standard Precautions. PMID- 17849726 TI - Getting ahead of the Pharmacy and Therapeutics Committee learning curve. PMID- 17849727 TI - The effect of the Medicare Part D benefit on medication management. PMID- 17849728 TI - Rheumatoid arthritis: a rapidly evolving treatment paradigm. PMID- 17849729 TI - Current management of rheumatoid arthritis. AB - Rheumatoid arthritis (RA), the most common form of inflammatory arthritis, is a chronic, inflammatory, progressive disease. Most patients have moderate disease, with a variable disease course and symptomatic flares interspersed with periods of relatively lower disease activity. Over the last 2 decades, the treatment of RA has evolved dramatically, from use of disease-modifying antirheumatic drugs to newer biologics. None of these therapies represents a cure for RA; however, the availability and the efficacy of multiple treatments has made remission of the disease a realistic target. PMID- 17849730 TI - A conversation with Arthur Kavanaugh. AB - Biologic therapies play a greater role in the treatment of human autoimmune diseases than they did in the past. Arthur Kavanaugh, MD, Professor of Clinical Medicine, University of California, San Diego, School of Medicine, talked with Managed Care Interface about the use of these agents, ongoing research in this area, and genetic factors that can come into play when treating rheumatoid arthritis. PMID- 17849731 TI - Back to the future: the managed care approach to rheumatoid arthritis. AB - Biologic disease-modifying antirheumatic drugs have been proven effective in the treatment of rheumatoid arthritis, but their efficacy literally comes at quite a high price to health plans. Therefore, MCOs are examining various strategies to provide coverage for these agents in a more cost-effective manner. PMID- 17849732 TI - Direct economic effect following mupirocin therapy failure among patients with uncomplicated skin and skin-structure infections in a large population-based cohort. AB - The goal of the study was to derive initial costs associated with failure of initial mupirocin therapy among patients diagnosed with uncomplicated skin and skin-structure infections (uSSSIs). A retrospective observational analysis of medical, pharmacy, and enrollment records was conducted using data from the National Managed Care Benchmark Database. Patients were classified as failing treatment with mupirocin if they either filled a second antibiotic commonly used to treat uSSSIs five to 30 days after their index mupirocin prescription fill or experienced a uSSSI-related hospitalization within 30 days after the index mupirocin prescription fill. Among 12,650 failure episodes, 11,867 (93.8%) required a second antibiotic contributing a mean cost of $62 per prescription. Approximately 4,782 (37.8%) had an associated outpatient encounter resulting in a mean cost of $221 per encounter. Nine percent of failures required a hospitalization with a mean cost of $6,597 per hospitalization. These medical, hospital, and pharmacy costs translated into an expected cost of $735.45 per mupirocin failure among patients with uSSSIs. The management of uSSSIs is costly in terms of health care resource use and direct health care expenditures when initial therapy with mupirocin fails. PMID- 17849733 TI - Thinking differently about health. PMID- 17849734 TI - Changes since the turn of the century. PMID- 17849735 TI - Disorders of sexual development--still a big challenge! PMID- 17849736 TI - Bariatric surgery in pediatrics--is it time? AB - In view of the increasing prevalence of obesity all over the world, we have seen morbid obesity occurring at earlier ages, and especially in adolescents. The first and main approach has been a conservative one, including change of lifestyle - implying better feeding habits and physical activity. However, our weapons to deal with this 'pandemic of obesity' have not solved a large number of cases, and we have to admit that bariatric surgery should be contemplated in special cases. Many different approaches have been devised by bariatric surgeons and although the complications over the short- and long-term are high and potentially severe, in some cases it is the only approach that has the potential to put the patient back to a more 'normal' metabolic situation with a significant weight loss. We discuss the main surgical approaches for morbid obesity and we comment on the pros and cons of each of them. PMID- 17849737 TI - LWPES 35 years: our heritage and our destiny. PMID- 17849739 TI - Low-dose adrenocorticotropic hormone stimulation testing in term infants. AB - BACKGROUND: Low-dose adrenocorticotropic hormone (ACTH) stimulation testing is a commonly accepted way to evaluate adrenal function in children. However, there are no published data on the use of this test in term infants less than 12 months of age outside the newborn period. METHODS: We identified 14 infants at our center who were full term and had one or more ACTH tests at less than 12 months of age to evaluate for secondary adrenal insufficiency (AI). We retrospectively assessed peak cortisol response in these infants to determine whether a cut-off of 20 microg/dl is appropriate to distinguish normal from abnormal adrenal function in this age group. RESULTS: Five infants had peak cortisol > or =20 microg/dl on their first ACTH test and had a clinical picture consistent with normal adrenal function. Nine infants had peak cortisol <20 microg/dl on their first ACTH test. When retested later in infancy, four of these patients achieved peak cortisol > or =20 microg/dl. CONCLUSIONS: In term infants, the low-dose ACTH stimulation test is useful for demonstrating normal adrenal function but is of limited value in diagnosing secondary AI. For infants with peak cortisol <20 microg/dl, clinical observation and repeat ACTH testing later in infancy clarified diagnosis. PMID- 17849738 TI - Congenital goiter in premature twins due to propylthiouracil treatment. PMID- 17849740 TI - Adrenal function in children with severe asthma treated with high-dose inhaled glucocorticoids: recommended screening tests in outpatient conditions. AB - BACKGROUND: A number of previous studies have suggested that adrenal suppression occurs in asthmatic children treated with high-doses of inhaled glucocorticoids (IGC). This study was designed to determine the frequency of adrenal suppression in children with severe asthma treated with recommended doses of IGC: namely 500 1,000 microg/day of fluticasone propionate or the equivalent of budesonide (1,000 2,000 microg/day) for a period of at least 12 months. METHODS: Early morning cortisol (F) and ACTH serum levels were measured in 27 severe asthmatics aged 6 16 years old. The children underwent a low dose ACTH test (1 microg/1.73 m2) with a parallel glucose measurement. Twenty-four hour urine collection was performed before examination for free F (UfF) and creatinine levels. There were no clinical manifestations of adrenal hypofunction in the analyzed children. RESULTS: Of the 27 patients, 22 had normal basal and post-stimulatory levels of F and normal UfF, and the other five (18.5%) had basal serum F levels of <400 nmol/l. Four of the five also had normal post-stimulatory levels of F and normal UfF. One child had a subnormal peak F value of 484 nmol/l during the ACTH test. None of the patients had a suppressed serum ACTH level, but an elevated ACTH level was found in four children. This study provided biochemical evidence of suboptimal adrenal function in one child in the examined group (3.7%) and a good response to stimulation in all the others, even in those with slightly reduced basal cortisol levels. CONCLUSION: This study showed that the use of fluticasone in doses of up to 1,000 microg/day (or the equivalent of budesonide) as long-term treatment of children with severe asthma did not substantially affect their adrenal function. PMID- 17849741 TI - Prevalence of micropenis among boys from different regions of Bulgaria. AB - AIMS: Micropenis is a normally formed penis whose length is more than 2.5 SD below the mean penile length for age. However, the definition of this disorder depends on penile length norms. METHODS: Penile length, circumference and anthropometric values of 310 boys under one year of age from five regions in Bulgaria were investigated. RESULTS: The mean penile length for all boys was 3.55 +/- 0.46 cm, thus micropenis could be defined as a penile length below 2.40 cm. However, regional differences were observed in penile length and circumference. According to regional mean values and the appropriate definition of micropenis, only two of the children had micropenis. CONCLUSIONS: In a prospective study of Bulgarian boys we established wide regional variations of normal penile length. Consequently, the diagnostic and therapeutic approach to micropenis should consider the mono-ethnic inter-regional differences. PMID- 17849743 TI - Usefulness of the long-acting insulin analogue glargine in basal-bolus therapy for Japanese children and adolescents with type 1 diabetes mellitus. AB - The aim of this study was to evaluate the efficacy of long-acting insulin analogue glargine (G) changing from NPH in basal-bolus therapy for Japanese children and adolescents with type 1 diabetes mellitus (DM1). Thirty patients (11 M, 19 F) with DM1 aged 13.3 +/- 4.5 years were included in the study. Mean fasting blood glucose level was significantly decreased (baseline: 142.5 +/- 39.3 vs 127.1 +/- 24.0, 129.0 +/- 29.1, 121.1 +/- 26.0 mg/dl at 3, 6, 12 months, respectively, p <0.01), and mean HbA(1c) was significantly decreased (baseline: 8.06 +/- 0.85 vs 7.69 +/- 0.89, 7.57 +/- 0.93, 7.36 +/- 0.95%, at 3, 6, 12 months, respectively, p <0.01) after changing to G from NPH. Severe hypoglycemia rarely occurred during the study period. In conclusion, basal-bolus therapy using G resulted in improved overall glycemic control with a low risk of severe hypoglycemia in Japanese pediatric patients with DM1. PMID- 17849742 TI - C-reactive protein levels and their relationship with metabolic syndrome and insulin resistance in Mexican adolescents. AB - OBJECTIVE: To investigate the relationship of high sensitive C-reactive protein (hs-CRP) with metabolic syndrome components and insulin resistance in Mexican adolescents. METHODS: 325 adolescents, 182 girls and 143 boys, aged 12-16 years were studied. Standardized clinical measurements and plasma lipids, glucose, insulin and hs-CRP were determined. For metabolic syndrome (MS), the NCEP-ATP III definition was used. RESULTS: MS prevalence was 13%. The most frequent MS components were low HDL-C (50%), high triglycerides (35%), and high waist circumference (28%). hs-CRP median and 75th percentile values for all children were 0.42 and 0.97 mg/dl, respectively. The highest values of hs-CRP were found in children who had MS, p <0.007. hs-CRP was positively correlated with waist circumference, triglycerides, and negatively with HDL-C, p <0.01, and positively with insulin, p <0.001. In stepwise multiple regression analysis, body mass index and HOMA-IR accounted for 10.4% and 12.7% of hs-CRP levels, respectively. CONCLUSIONS: Body mass index and insulin resistance have an independent effect on high hs-CRP levels, and explain a large part of hs-CRP concentrations in adolescents. Central adipose tissue might induce an inflammatory state that could be identified from adolescence. PMID- 17849744 TI - Prevalence of vitamin D insufficiency in obese children and adolescents. AB - OBJECTIVE: Recent studies have shown a broad prevalence of vitamin D deficiency in adults. Serum 25-hydroxyvitamin D (25-OHD) levels were reported to be inversely related to body mass index (BMI) and body fat content and correlated directly with hypertension, degree of insulin resistance and progression to diabetes mellitus. We sought to determine the prevalence of vitamin D insufficiency and markers of metabolic syndrome in an obese pediatric population. METHODS: Charts of 217 obese (weight >95th percentile for age and sex) children (118 females, 99 males; mean BMI 32.2 +/- 6.4 kg/m2; mean age 12.9 2 5.5; age range 7-18 years) who had received a standard physical examination at the pediatric endocrine clinic of the Infants and Children's Hospital of Brooklyn at Maimonides, Brooklyn, NY, were retrospectively analyzed. Data obtained included age, sex, weight, BMI, height and systolic and diastolic blood pressure. The routine bloodwork panel for obesity at our pediatric endocrine facility includes fasting 25-OHD, total cholesterol, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides, ALT, AST, thyroid stimulating hormone (TSH), total T4, and insulin and glucose. Insulin sensitivity as calculated by quantitative insulin-sensitivity check index (QUICKI = 1/[log(I0) + log(G0)], where I0 is fasting insulin and G0 is fasting glucose) was computed following the visit. RESULTS: Overall, 55.2% of patients were vitamin D insufficient (25-OHD <20 ng/ml). Severely low vitamin D levels (25-OHD < or =10 ng/ml) were seen in 21.6% of 217 patients, which represents almost half of the insufficient group. In the 25-OHD <20 ng/ml group age, BMI, and SBP were significantly higher than in the 25-OHD 220 ng/ml group, while QUICKI (<0.35 is consistent with insulin resistance) was borderline low in the <20 ng/ml group. HDL-C was significantly lower in the 25-OHD < or =10 ng/ml group. The 25-OHD levels correlated negatively with BMI and positively with HDL-C. No other findings were significant. CONCLUSION: More than half of the obese children had vitamin D levels <20 ng/ml with equal gender distribution. Vitamin D insufficiency was associated with increased age, BMI, and SBP, and decreased HDL C. PMID- 17849746 TI - Infantile systemic hyalinosis with early thyroid dysfunction. AB - Infantile systemic hyalinosis is an autosomal recessive disorder characterized by diffuse hyaline deposits in the skin, gastrointestinal tract, muscles and glands. The molecular basis of infantile systemic hyalinosis is unknown. The main pathological feature is widespread hyalinosis of many tissues and organs. We present an 18 month-old girl with infantile systemic hyalinosis and hypothyroidism. Newly diagnosed children with infantile systemic hyalinosis should have thyroid studies as a routine part of diagnostic work-up. PMID- 17849745 TI - Identification of a novel mutation in the human growth hormone receptor gene (GHR) in a patient with Laron syndrome. AB - Deletions and mutations in the growth hormone receptor (GHR) gene are the underlying etiology of Laron syndrome (LS) or growth hormone (GH) insensitivity syndrome (GHIS), an autosomal recessive disease. Most patients are distributed in or originate from Mediterranean and Middle-Eastern countries. Sixty mutations have been described so far. We report a novel mutation in the GHR gene in a patient with LS. Genomic DNA sequencing of exon 5 revealed a TT insertion at nucleotide 422 after codon 122. The insertion resulted in a frameshift introducing a premature termination codon that led to a truncated receptor. We present clinical, biochemical and molecular evidence of LS as the result of this homozygous insertion. PMID- 17849747 TI - Can insulinoma cause generalised epilepsy? AB - Insulinoma is a common cause of seizures due to recurrent hypoglycemic crises. Surgical treatment usually results in disappearance of such seizures. We describe a previously healthy 17 year-old girl who became epileptic after the onset of insulinoma with persistent seizures after surgical removal of the tumour. Insulinoma must be taken into account for differential diagnosis with convulsions of unknown origin, and even after metabolic normalization it may cause epilepsy. PMID- 17849748 TI - Tumor induced hypercalcemia in a patient with mediastinal synovial sarcoma. AB - Tumor-induced hypercalcemia is a frequent complication of advanced cancers, but it has been rarely reported in patients with sarcoma. We report a 16 year-old boy presenting with polyuria, polydipsia and severe dehydration. Laboratory examination revealed severe hypercalcemia (serum calcium 23 mg/dl) which caused emaciation and was accompanied by low serum phosphorus and suppressed parathyroid hormone. Diagnostic imaging revealed a huge anterior mediastinal mass. Hypercalcemia was successfully treated with pamidronate, a bisphosphonate, and the patient underwent surgical resection. Pathological and immunohistochemical analyses confirmed a diagnosis of biphasic synovial sarcoma. To our knowledge, this is the first case of mediastinal synovial sarcoma presenting with hypercalcemia. PMID- 17849749 TI - Measure for measure: developing benchmarks for clinical engineering activities: a methodology. PMID- 17849750 TI - The road less traveled: alternate careers for BMETs. PMID- 17849751 TI - Flipping the switch...teamwork, communication help hospital avert potential disaster. PMID- 17849752 TI - Children's Hospital of Philadelphia...smaller patients, but no smaller challenges. PMID- 17849753 TI - Dialysis: a complex modality for life. PMID- 17849754 TI - The basics of power cord specs. PMID- 17849755 TI - E-mail alerts help biomed department manage its business. PMID- 17849756 TI - Suction devices: troubleshooting in a vacuum. PMID- 17849757 TI - TIFF, GIF, and PNG: get the picture? AB - GIF, JPEG, and PNG are most likely the best formats to use for three reasons. First, they're standardized and open formats for anyone to use. In addition, JPEG is an ISO standard and PNG is an IETF RFC (Internet Engineering Task Force Request for Comments-www.ietf.org) and W3C recommendation (World Wide Web Consortium-www.w3.org). Second, they're compressible. GIF files are generally compressed at 5:1, JPEG at 10:1 or 20:1 and PNG at about 7:1. Finally, they're all supported by web browsers. Well, pretty much. Microsoft's Internet Explorer doesn't support the alpha channel transparency for PNG-but, on the other hand, GIF and JPEG don't have the alpha channel at all. Use TIFF to archive your original pictures as it is a lossless format. Check out the summary table and sidebar for more information regarding these picture file formats. PMID- 17849758 TI - Pacemakers. PMID- 17849759 TI - Risk-based validation of multilingual medical devices. PMID- 17849760 TI - State of the surveys: 18 months of joint commission unannounced visits. PMID- 17849761 TI - Patient safety: clinical engineering in the trenches at Hamilton Health Sciences. PMID- 17849762 TI - Standards and copyright: finding a balance. PMID- 17849763 TI - Stethoscopes: what are we hearing? AB - This paper develops an objective methodology to test the audio quality of stethoscopes, classifies stethoscopes into five functional categories, and compares the audio performance of each of the five categories. These categories, based on the manufacturer's recommended use, are basic assessment, cardiology, disposable, high-end cardiology, and physical assessment. The classification into categories is based on the intended performance of the stethoscopes as provided by the manufacturers. After developing the procedures and running more than 500 tests, the stethoscope with the least amount of loss over the spectrum was chosen from each of the five categories; the five were then compared to one another. Thirty-nine stethoscopes from 11 manufacturers were used in this study. The objective test methodology allows for side-by-side comparison of stethoscopes from various manufacturers that is independent of the manufacturer's published test results. PMID- 17849764 TI - A designed experiment for evaluation of the OPA method for cleaning studies of medical devices. AB - This study reports the results of a designed experiment to evaluate the use of the o-phthalic dialdehyde (OPA) method for residual protein, with a testsoilderivedfrom blood, dehydrated hog mucin, and egg yolk, and its application in validating the automated cleaning of surgical instruments in a laboratory setting. The ruggedness and robustness of the OPA method was determined by means of a Plackett-Burman experimental design and assessed the automated cleaning of a microkeratome for use in patients undergoing lamellar resection of the cornea during refractive surgery. The outcome of the study indicates that the OPA method for residual protein is rugged and robust for the factors evaluated and is an effective means for validating the cleaning of complex medical devices under controlled laboratory conditions. The components of the microkeratome contaminated with the test soil were successfully cleaned in an automated washer-disinfector using a neutral pH detergent and the procedure as described. PMID- 17849765 TI - On sculpture, baseball, and benchmarking... PMID- 17849766 TI - The cost of cutting family health services. PMID- 17849767 TI - How accessible is child care today? AB - The Government's 10-year child care strategy and the Childcare Act 2006 have established the framework for improving the provision of good quality child care for parents who need it in the UK. The number of day places for child care has increased, especially for full-time care and out-of-school clubs. There is now one place for every three children aged under eight years, but much needs to be done before care is available to all parents who need it. The cost of child care has risen above inflation and care for one child currently costs about one-third of the weekly earnings of a mother on an average wage. This puts child care beyond the reach of some low-income parents. There is a shortage of places for children with disabilities and for children of parents working outside normal office hours. Although efforts are being made to establish a better qualified and professional child care workforce, low pay and status make it difficult to recruit and retain suitable, high quality staff. More investment is needed in day care to bring the UK up to the level of Scandinavian countries. PMID- 17849768 TI - Where do parents go for child care advice? AB - Parenting advice is now available from a wide range of sources. Informal networks and written literature provide first-line support, but advice from health care professionals remains highly important. The health professional's skill centres on knowing what advice and approach to information giving is appropriate for an individual situation. It is also important to respect and understand cultural influences in individual communities, and work with such forces to ensure that the community as a whole understands why specific child care practices are important. PMID- 17849769 TI - Fat--our genes or our fault? PMID- 17849770 TI - Encouraging healthier lifestyles--3. Healthy living for all the family! AB - The link between good nutrition, exercise and health is well established, but many people in the U.K. still do not follow the nationally recommended guidelines for either nutrition or exercise. The problem affects children and young people as well as adults and puts them at risk of several chronic diseases in later life such as diabetes, heart disease and obesity. This article looks at some practical ways of tackling poor nutrition and lack of exercise in families, since the family has a strong and lasting influence on children's health behaviours and parents are powerful role models for their children. PMID- 17849771 TI - Does childhood nutrition matter? AB - Nutrition in childhood influences both the child's present and future health. Health professionals need to educate parents from all socioeconomic groups about good nutrition for their children from birth onwards. They should give priority to including this during consultations. All parents must be made aware of the nutritional benefits of breast-feeding. Since most babies receive formula at some stage during the first year of life, health professionals also have a responsibility to be aware of current developments in infant formulae (e.g. nucleotides, long chain polyunsaturated fatty acids, prebiotics) so they can give accurate information. Weaning is an important nutritional milestone with implications for present and future health. Advice on good weaning practice should be a priority and can help avoid several nutritional problems later on, such as excessively faddy eating, faltering growth, constipation, iron deficiency anaemia and obesity. The last two are key problems in children in the U.K. today. Families should be encouraged to cook, eat and enjoy food together as often as they can, which in itself has been shown to have nutritional benefits, as well as considering the quality of the food they eat. PMID- 17849772 TI - Baby-feeding support: a view from the coalface. AB - The author gives her views on some of the problems of baby-feeding support in the community. There appear to be inconsistencies in the way "breast-feeding" is defined, which can lead to confusing data and may inflate the figures for hospital breast-feeding rates. Early discharge of mothers after a birth and shortage of community midwives make it more difficult for mothers to establish breast-feeding. Support for both breast-feeding and bottle-feeding mothers is often lacking. The author describes an inclusive support group that welcomes mothers whether they are exclusively breast-feeding, partially breast-feeding, or bottle feeding. PMID- 17849773 TI - Neurofibromatosis: a guide to care in the community. AB - Neurofibromatosis (Nf) comprises a group of conditions that cause benign tumours on the nervous system. It encompasses at least two distinct disorders, neurofibromatosis type 1 (Nf1) and neurofibromatosis type 2 (Nf2). These two conditions differ genetically, but both pose complex health problems. The Nf1 gene was identified on chromosome 17 in 1990 and the Nf2 gene on chromosome 22 in 1992. If the genetic mutation is identified in an individual, genetic prenatal testing is possible. The genetic variability, the range of multisytem clinical features and the unpredictability of the disorder fill many people with fear and anxiety. Nf has significant impact on quality of life through alteration of the patient's health and appearance, and there is no doubt that it affects the lives of the patient's whole family. In the U.K., the charity The Neurofibromatosis Association (NfA) offers information and support for patients, families and health professionals and funds specialist advisers in regional genetics centres throughout the UK. Where specialist advisers are in post, a number of specialist Nf1 and Nf2 clinics have evolved. The role involves direct liaison with schools to provide guidance on educational problems, as well as responding to the needs of the individual and family. PMID- 17849774 TI - Passionate about community midwifery! PMID- 17849775 TI - Who needs vitamin supplements? PMID- 17849776 TI - Practice guideline for the treatment of patients with obsessive-compulsive disorder. PMID- 17849777 TI - [Dislocated port system. Twisted life]. PMID- 17849778 TI - [Pregnant after rape. Is late abortion justifiable?]. PMID- 17849779 TI - [Dangers in diving under and in coming up]. PMID- 17849780 TI - [With new strategies against vaccination gaps in adulthood]. PMID- 17849781 TI - [Kidney transplantation--standard method for terminal kidney failure. More sucess through living donation]. PMID- 17849782 TI - [The blood group incompatible living kidney transplantation]. AB - Until recently, living kidney donations between donors and recipients of different blood groups were contraindicated. Since 2004, blood group incompatible kidney transplantations have been performed in Germany. Through the use of the anti-CD20 antibody rituximab and a highly selective immunoadsorption treatment, the recipient's antibodies against the foreign blood group are removed before the transplantation to minimize the risk of an antibody-mediated acute rejection reaction after the transplantation. PMID- 17849783 TI - [Kidney transplantation with simultaneous nephrectomy: inappropriate or sensible?]. AB - In conventional single kidney transplantation, the patient's kidneys are left in place. However, in certain patient collectives, the removal of the kidney may be indicated under some circumstances. This applies especially to patients whose own kidney may be a source of infection, bleeding, severe proteinuria and physical impairment due to a considerable increase in the kidney volume (cystic kidneys). Up until now, the procedure planned for either a bilateral nephrectomy after inclusion on the waiting list or a sequential procedure, which involves nephrectomy of one kidney and the removal of the other after kidney transplantation (sandwich technique). The concept presented here, kidney transplantation with concomitant ipsilateral nephrectomy is a safe procedure that leads to neither a significant increase in the incidence of surgical complications nor to a decrease in patient-and transplant survival. The major advantage of this method, in addition to a high measure of patient satisfaction, is the definitive surgical restoration of the kidney transplant recipient on the transplanted side with only one surgical intervention. PMID- 17849784 TI - [Emergency checklist: angioedema]. PMID- 17849785 TI - [Active treatment and sustained compression. Venous leg ulcer--exemplary care]. PMID- 17849786 TI - [ECG quiz for the family doctor]. PMID- 17849787 TI - [Pioglitazone protects the type-2-diabetes patient from myocardial infarction and stroke]. PMID- 17849789 TI - [Pioneers with partners]. PMID- 17849790 TI - [Fee charges are fully to be claimed]. PMID- 17849792 TI - [Prevalence of hymenoptera sting allergy in veterinary medicine students from Monterey, Nuevo Leon, Mexico]. AB - BACKGROUND: The reported prevalence of allergic systemic reactions to hymenoptera venom occur in up to 3.3% and large local reactions occur in 17% in the general population. OBJECTIVE: To investigate the prevalence of hymenoptera sting allergy in a group of veterinary medicine students from Monterrey, Nuevo Leon, Mexico. PARTICIPANTS AND METHODS: A transverse and observational study was done with 64 students of veterinary medicine. We conducted a questionnaire about the students' history of insect allergy and atopy. Skin test with allergenic extracts of bee and ant were practiced to all subjects. We performed aeroallergen skin prick test to the subjets with suspected atopy. RESULTS: Students age ranged from 17 to 25 years (mean 20.2) and 37 were males. Twenty students (31.3%) had clinical history of atopy and positive skin tests to aeroallergens. On the other hand, 5 students (7.8%), including 2 atopic, had suffered large local reactions, but none of them had suffered systemic reactions. Bee and ant skin tests were positive in 15.6% and 31.3% of the students respectively. There was no difference in the prevalence of hymenoptera allergy between atopic and non atopic subjects (p < 0.05). Further, the frequency of atopy in subjects with positive skin tests for bee and ant was 50%. CONCLUSION: The prevalence of large local reactions and hymenoptera sensitization found in this group was similar to that found in other epidemiologic studies. PMID- 17849791 TI - [Effects of methimazole on the evolution of the allergic rhinitis of patients with Graves' disease]. AB - BACKGROUND: The methimazole has long been used for treating Graves' disease to decrease thyroid hormone production and obtain a thyroid normofunction, but this drug has also immunosuppressive and immunomodulation effects. OBJECTIVE: To analyze in patients with Graves' disease treated with methimazole and allergic rhinitis, the clinical evolution of the allergic rhinitis with the immunosuppressive and immunomodulation effects of the methimazole. PATIENTS AND METHODS: A comparative and observational study was done in the Mexico's General Hospital, in twenty-six patients with Graves' disease treated with methimazole 10 mg, thyroid profile was done, and when subjects obtained a thyroid normofunction continued with the same doses of methimazole and received also 12.5 mcg/day of levothyroxine. All the patients were diagnosed with allergic rhinitis, and they were divided into two groups (11 females and 2 males each). Both groups continued with the same treatment of methimazole and levothyroxine, but group II was given also antihistamines H1 of second-generation (loratadine) daily, and specific immunotherapy during six months. We described and compared the clinical evolution of the allergic rhinitis of the two groups with the treatment. RESULTS: In the group I, changes in the clinical evolution of the allergic rhinitis after six months were not observed. In the group II, by week 10 the symptoms of the allergic rhinitis were controlled in 80% of the patients, and by week 14 all the patients of this group were asymptomatic. CONCLUSIONS: In patients with allergic rhinitis and Graves' diseases with methimazole-thyroid normofunction we observed that there is not influence of methimazole on clinical evolution of the allergic rhinitis. PMID- 17849793 TI - [Costs due to asthma medical care in a group of children from northeastern Mexico]. AB - BACKGROUND: In 1998 the economic burden of asthma in the United States was estimated in 12.7 billion dollars. In Mexico the annual direct costs for asthma could be approximately from 32 to 35 million dollars. OBJECTIVE: To estimate the healthcare costs in asthmatic children in the Northeast of Mexico. MATERIAL AND METHODS: A descriptive cross-sectional study was performed. We applied a questionnaire to the parents of 60 asthmatic children. They attended to a conference about asthma and allergy illnesses. In this questionnaire the parents answered some questions that provided us information about expenditures because of the treatment of their children with asthma during the last year. RESULTS: Fifty-six questionnaires were answered correctly. The mean age of children was 10.8 +/- 2.5 years and 64.3% of them were males. The annual costs reported by patient were < or = 225 USD for medical consultation (76.8%) and < or = 134 USD for immunotherapy (81.6%). On the other hand, the costs for emergency department visits and hospitalization were < or = 45 USD and < or = 180 USD by each event respectively. CONCLUSIONS: The costs of asthma treatment in children are considerable and cause a huge impact in the family economy. It is necessary further research in bigger groups and doing comparative studies among different groups will help clarify the extent of the economic burden of asthma in Mexico. PMID- 17849794 TI - [Adverse reactions to vaccines]. AB - Vaccination is one of the medicine's achievements to control and/or eradicate certain infectious diseases. Vaccines contain antigenic doses derived from microorganisms and/or its toxins, besides they are composed of other substances such as aluminum, gelatin, egg proteins, mercury components (as thimerosal), and antibiotics; therefore, these substances can produce hypersensitivity reactions. The above-mentioned reactions can be evidenced with itch, edema, hives, asthmatic crisis, hypotension and even anaphylactic shock. Due to the importance of vaccination, especially in childhood, it is essential to know the benefits of vaccines, their impact in morbidity and mortality decrease of certain infected contagious diseases, as well as the adverse effects and the allergic reactions to their application. As immunizations prevent natural infections, they might contribute to a free infectious environment that would allow atopic response. This paper reviews the allergic reactions to vaccines and their influence on the development of atopic disease. PMID- 17849795 TI - [Uncommon manifestations of atopic dermatitis]. AB - Atopic dermatitis is an inflammatory process characterized by a series of cutaneous alterations of typical morphology and distribution, with intense pruritus of nocturnal predominance, of chronic evolution, stational appearance, and with personal and family history of atopy. On genetically predisposed skin, dry and hypersensitive, the immune factors and other types are implicated in determining the abnormal reactions to multiple endogenous and environmental factors. The diagnosis is clinical, generally obtained by a group of signs and symptoms known as the Hanifin and Rajka criteria. The patients with atopic dermatitis can present with clinical typical manifestations, or minimized and localized variations as well, considered a stigma of atopic constituent. In some patients there can be observed clinical and morphological variations with special localizations denominated atypical variations of atopic dermatitis. The identification of these atypical presentations of atopic dermatitis leads to the differential diagnosis, with an early establishment of the disease's diagnosis and the appropriate and early treatment. PMID- 17849796 TI - [Clinical effects of metformin in patients with polcystic ovarian syndrome]. AB - OBJECTIVE: To verify the medical effects of metformin in polycystic ovary syndrome patients. METHOD: 10 women with polycystic ovary syndrome were including in this prospective clinical study. After a baseline workup, body mass index (BMI) and waist hip index (WHI) were measured; the diagnosis of polycystic ovary syndrome was achieved with the following basal clinical studies: vaginal ultrasound, prolactin, thyroid profile, glucose, insulin, testosterone, androstenedione, 17-hidroxiprogesterone, dehydroepiandrosterone sulfate and cortisol. The diagnosis of insulin resistance was achieved by model homeostasis assessment and the relationship glucose/insulin. Patients were given 500 mg of metformin twice a day for 3 months and reevaluated. RESULTS: 8 of 10 patients who completed treatment, showed significant improvement in insulin resistance (only by homeostasis model); there were decrease in hirsutism (mean of 35.07%), without improve menstrual cyclicity, although we achieved at least one menstruation in 42.85% in cases with amenorrhea after 2 or 3 months of treatment. There were no changes in weight, BMI neither in ovarian volume and number of follicles. CONCLUSION: A 3 month course of metformin therapy in women with polycystic ovary syndrome did not improve menstrual cyclicity, albeit significant decrease in insulin, insulin resistance and hirsutism was obtained. PMID- 17849797 TI - [Ureteral injury at the National Institute of Perinatology]. AB - OBJECTIVES: To evaluate the incidence of ureteral injury at Instituto Nacional de Perinatologia and to know the variables associated to ureteral injury as a ginecoobstetric surgery complication, and to do a theme review. MATERIAL AND METHODS: We conducted a study including patients with ureteral injury from January 1st 1992 to July 1st 2005. Files were registered for age, parity, surgery associated to the injury, injury type, diagnostic time and methods, management type and evolution. The study was observational, transversal, and retrospective. We analyzed the results with descriptive statistics. RESULTS: We included 39,405 surgeries; a total of 32 injuries were identified, and in 41% the injured ureter was the left one, in 42% was the right one and both in 17%. We included patients from the Instituto and from another hospital. Mean age was 38.9 years, media 43 and mode 44 years. Principal surgery related was the gynecological histerectomy. Patients' evolution was satisfactory. The most frequent surgery to repair the ureter was the reimplantation, followed by the immediate reparation with simple stitches. CONCLUSIONS: The ureteral injury frequency was 0.04%, in relation principally with gynecological histerectomy. The most frequent injury type was the ligation in the distal third. In three cases there was a ureter-bladder fistula. The ureteral reimplantation was the most frequent surgical repair. PMID- 17849798 TI - [Correlation between Doppler fluxometry of middle cerebral artery/umbilical and non stress test as methods of antepartum fetal surveillance]. AB - OBJECTIVE: To determine the correlation between Doppler fluxometry of middle/umbilical cerebral artery and the non-stress test as methods of antepartum fetal surveillance. PATIENTS AND METHODS: We made a cross-sectional study. There were included 161 patients with high risk pregnancies. We carried out the non stress test and the middle/umbilical cerebral artery resistance index in these women. Apgar score and perinatal outcome of the newborns were registered. Correlation coefficient as well as the sensitivity, specificity and predictive values of the tests were calculated. RESULTS: For the non-stress test in perinatal death, a sensitivity of 0% and a specificity of 84% were obtained; for Apgar at five minutes, sensitivity was 50% and specificity was 85%. In relation to perinatal death, the middlelumbilical cerebral artery resistance index has a sensitivity and specificity of 100 and 91%, respectively; for Apgar score at five minutes, the values were 100 and 92%, respectively. Correlation coefficient for the middle/umbilical cerebral artery resistance index and the non-stress test was -0.257 (p = 0.0009). CONCLUSION: We found a correlation between the middle/umbilical cerebral artery resistance index and the non-stress test. This index had more sensitivity and specificity for diagnosing perinatal death and Apgar score, for this reason we recommend it as a first choice method of antepartum fetal surveillance. PMID- 17849799 TI - [Change of pulsatile release and luteinizing hormone response to naloxone related to testicle damage]. AB - OBJECTIVE: To compare the pulsatile release of LH, the tone of endogenous opioids and the mass of LH secreted after a naloxone infusion in healthy subjects and patients with normogonadotropic oligospermia (NO) in a model of progressive testicular damage. PATIENTS AND METHODS: Pulsatile secretion of LH was analyzed in a period of 8 hours in a group of healthy subjects (group 3, n=5), in patients with NO and FSH/LH ratio <1.6 (group 1, n=5) and in patients with NO and FSH/LH ratio >1.6 (group 2, n=5). The area under the curve of LH response after naloxone infusion was also calculated. RESULTS: Free serum testosterone concentration was lower (p < 0.01) and estradiol concentration higher in patients with NO than control subjects (1 vs. 3: p = 0.01; 2 vs. 3: p = 0.001). Frequency of pulses in group 1 was 3.33 +/- 0.57/8 h, in group 2: 4 +/- 1/8 h; and in group 3: 2.66 - 0.57/8 h (2 vs. 3 p < 0.01; 2 vs. 1 p = 0.05). The area under the curve after naloxone infusion was 19,300.44 +/- 11,403.31 in group 1, 5696.09 +/- 1753.44 in group 2; and 3080.97 +/- 1159.78 in group 3 (1 vs. 3 Anova p = 0.01). CONCLUSIONS: The data indicate that patients with NO have a subclinical pantesticular failure and that the opioid tone is increased at the initial phase of testicular dysfunction, but it decreases at more advanced stages of testicular damage. PMID- 17849800 TI - [Cervical cancer and DNA microarrays: tumour marker identification]. AB - Microarray technology has remarkably accelerated the understanding of the molecular events of neoplasias. By means of gene expression profiles, a molecular subclassification of cancer patients and the identification of thousand of genes involved in this pathology have been achieved. Herein, the general use of DNA microarrays in cervical cancer tumorigenesis is reviewed. Finally, putative molecular tumour markers as useful factors in diagnosis, prognosis, and tailor made therapy for this disease are proposed. PMID- 17849801 TI - [Umbilical cord rupture and vasa previa: a report of a case]. AB - Vasa previa is a rare condition, frequently lethal, in which fetal blood vessels coming from the placenta or the umbilical cord cross the entrance of the childbirth channel before presentation. The abnormal blood vessels are result of a velamentous cord insertion or a placental alteration. It happens in 1:3000 births, with a high perinatal mortality. A 16 years-old primigest patient, at 34.6 week of gestation, was admitted to the labor, which has a good evolution, without any complication. A male new born was obtained without hearth rate or vitality, Apgar scale 0-0, weight 2800 grams, who presented an umbilical cord rupture 3 centimeters from its abdominal insertion, no where the fetal blood vessels are unprotected. It is necessary an adequate prenatal care, diagnosis and accurate management, to avoid the mortality by this rare clinical entity. PMID- 17849802 TI - [Cornual ectopic pregnancy. A report of a case and five-year-retrospective review]. AB - This article presents a clinical report of a cornual ectopic pregnancy as well as a five-year restrospective review of ectopic gestations at Hospital General de Matamoros Dr. Alfredo Pumarejo L, Tamaulipas, Mexico. The list with histopatological reports was checked up from January 2001 to May 2006. There were 66 results, of which only 31 files were complete. The presentation ages in these patients were between 16 and 39 years old, with a media of 25.6 years old and a mode of 21 years. The circumstances why patients attended to the hospital were: transvaginal bleeding and abdominal pain in 14 cases (45.1%), abdominal pain only in 12 cases (38.7%), and transvaginal bleeding only in five cases (16.2%). The clinical presentation was acute in 19 patients (61.3%), and it was insidious in 12 (38.7%). All women presented menstrual delay. Diagnoses were done by clinical findings in 12 women (38.7%), by clinical findings and ultrasonography in 18 (58.1%), and due to clinical findings and culdocentesis in just one patient (3.2%). Ectopic pregnancy was located in different places on each patient, such as: ampula, 24 cases (77.5%); isthmus, four patients (12.8%); fimbria, one case (3.2%); ovary, one woman (3.2%), and cornual in one patient (3.2%). Twenty-seven cases of broken ectopic pregnancies (87%), were found as transoperative findings, and the other four (13%) were not broken ectopic. There were not demises. Cornual ectopic pregnancy represents 1.5% of the ectopic gestations, as it is reported in the literature. PMID- 17849804 TI - [Deontological and ethical problems in gynecology. 1952]. PMID- 17849803 TI - [Diabetes insipidus and pregnancy]. AB - Diabetes insipidus is an uncommon pathology; its incidence varies from two to six cases in 100,000 pregnancies. It has multiple etiologies and it is classified in central and neurogenic. Patients with diabetes insipidus generally show intense thirst, polyuria, neurologic symptoms and hypernatremia. It does not seem to alter the patient's fertility. Diabetes insipidus is usually associated with pre eclampsia, HELLP syndrome, and fatty liver disease of pregnancy. This is a report of a case seen at the Hospital General de Cholula, in Puebla, Mexico. A 19 year old female, with 37.2 weeks of pregnancy, had a history of Langerhans cell histiocytosis since she was four years. Patient was treated with intranasal desmopressin until 2005. She went to an obstetric evaluation; laboratory and cabinet studies were obtained. A healthy 1900 g female was obtained through vaginal delivery, with a 7/9 Apgar score. We should be familiarized with this uncommon pathology because of its association with several obstetric emergencies. PMID- 17849805 TI - [Seminal quality and hormones in patients with diabetes mellitus type 2]. AB - INTRODUCTION: The role of the series of metabolic derangements associated to diabetes mellitus type 2 on the function of the hypothalamic-pituitary-testicular axis and on semen quality is still controversial due in part to the lack of information about the selection criteria of subjects included in previously published studies. This is important due to the high prevalence of occult pathology of the seminal tract. OBJECTIVE: To determine if diabetes mellitus type 2 is related to hormonal or seminal disorders. PATIENTS AND METHODS: In this retrospective study serum concentration of the hormones that regulate the hypothalamic-pituitary-testicular axis and semen quality were analyzed comparatively in patients with diabetes mellitus type 2 and normoglycemic subjects. In both groups occult seminal disorders and conditions associated to the hypothalamic-pituitary-testicular axis dysfunction were discarded. RESULTS: Serum concentration of FSH was higher in patients with diabetes mellitus type 2 than in controls (6.06 +/- 2.28 vs. 4.74 +/- 1.92, p = 0.04). Serum concentration of prolactin was lower in diabetics than in controls (6.71 +/- 1.28 vs. 8 +/- 1.97, p = 0.002). The only seminal abnormality found in patients with diabetes mellitus type 2 was a lower progressive mobility (46.52 +/- 17.77 vs. 58.88 +/- 16.81, p = 0.003). CONCLUSION: This suggests that the patients with diabetes mellitus type 2 have subclinical tubular dysfunction manifested by a low sperm progressive mobility and that this might be associated to subfertility. PMID- 17849806 TI - [Major and multiple birth defects in newborns of women attended in a tertiary care hospital]. AB - OBJECTIVE: To identify the frequency and type of major and multiple birth defects in live newborns of pregnant women attending at a tertiary care hospital. PATIENTS AND METHODS: A cross-sectional study was carried out during one year. There were included pregnant women who delivered neonates with a single major birth defect, or three minor birth defects, or one single major birth defect with two minor birth defects. A control group matched for sex without birth defects was included. We registered data of the mother, pregnant, newborn outcome and perinatal deaths caused by birth defects. RESULTS: Overall 17,546 pregnant women were included. There were 98 live newborns with birth defects (5.5 per 1000 live newborns). The most frequent birth defects were heart diseases (15.3%), gastrointestinal malformations (14.2%) and specific genetic syndromes (13.2%). Ten (13.2%) perinatal deaths were registered caused by birth defects. There were no difference between the groups in relation to maternal age, occupation, administered medications and number of appointments in antenatal care. Thirteen birth defects were diagnosed antenatal by ultrasound scanning. CONCLUSION: Since the repercussion of birth defects in the families and in hospital centers, it is important the collaborative work of a multidisciplinary team for diagnosing and treating these complications. These actions will contribute to enhance the outcome of the mother and newborn. PMID- 17849807 TI - [Hysteroscopy findings in patients with postmenopausal genital bleeding]. AB - OBJECTIVE: To describe morphological and histological findings in postmenopausal patients with abnormal uterine bleeding. PATIENTS AND METHODS: An open, descriptive, observational, retrospective and cross sectional study was done at Clinica de Histeroscopia at Hospital Dr. Manuel Gea Gonzalez, in Mexico City. There were included 372 patients with postmenopausal abnormal uterine bleeding diagnosis without hormone replacement therapy. Hysteroscopy study was made with a 5 mm surgical hysteroscope using warm saline solution (280C) as a medium of distension, and a trans-hysteroscopy endometrial biopsy was taken for histopathological correlation. Statistic analysis was obtained using SPSS program version 10 for windows with a kappa test. In order to analyze more than two samples, we used the chi-square test. RESULTS: Endometrial atrophy was the most frequent hysteroscopic diagnosis (202 patients, 54.3%), followed by polyps (93 patients, 25%), cancer (14 patients, 4%) and hyperplasia (11 patients, 2.95%). Correlated results between hysteroscopic findings and hystopathological biopsy diagnosis obtained were: atrophy (157 cases, 63.3%), polyps (76 cases, 77.55%), endometrial cancer (14 cases, 93.05%), endometrial hyperplasia (10 cases, 90.63%) and miomatosis (three cases, 16.20%). CONCLUSION: It can be stated that there is a high level of concordance between findings of hysteroscopic studies and the directed endometrial biopsy. So, we recommend initially the use of hysteroscopy for diagnosis and treatment of endometrial cavity malignant and benign pathology. PMID- 17849808 TI - [Relationship between domestic violence during pregnancy and risk of low weight in the newborn]. AB - OBJECTIVES: To determine the prevalence and characteristics of domestic violence before and during pregnancy, and its impact on obstetrical and perinatal outcomes, as well as to identify the main variables associated to domestic violence during pregnancy. PATIENTS AND METHODS: From August to September 2004, 288 consecutive women in the puerperium period were screened for a cross sectional study in the Hospital General Dr. Manuel Gea Gonz6lez. The Abuse Assessment Screen and the IPPF screening instrument were used to measure emotional and physical abuse during pregnancy. Outcome data included miscarriage, cesarean delivery, gestational age, birth weight and Apgar score. Odds ratios and 95% confidence intervals were calculated to measure the associations between maternal characteristics, perinatal outcome and violence. RESULTS: The prevalence of domestic violence during pregnancy was 39.24%. Emotional abuse was the most prevalent type before and during pregnancy (94.71 and 96.46%, respectively) whereas the frequency of physical and sexual decreased during pregnancy. Domestic violence 12 months before pregnancy increased risk of low birth weight (OR: 1.69; 95% CI: 1.01-2.81), and miscarriage (OR: 2.09; 95% CI 1.14-3.83). The exposure to domestic violence anytime before pregnancy (OR: 3.13; 95% CI 1.48-6.63) and 12 months before pregnancy (OR: 12.79; 95% CI 6.38-25.6) increased risk of domestic violence during pregnancy. CONCLUSIONS: Violence before and during pregnancy is common and is associated with adverse maternal and perinatal outcomes. There is a critical need to include a routine screening in the obstetric and gynecologic services and to provide medical and social services. PMID- 17849809 TI - [Psychological symptoms in a group of climacteric women, before and after a psychotherapeutic process]. AB - BACKGROUND: Two of each three women in their menopause present climacterical syndrome, showing frequently psychological symptoms, which is translated in diminution of the personal satisfaction, which generates the necessity of specialized attention. OBJECTIVE: To know the presence and frequency of psychological symptoms, before and after a psychotherapeutic process with a psychodynamic approach, in a group of women in their menopause. PATIENTS AND METHOD: The sample consisted of 41 women divided in two groups, with pre and post application of the survey of symptoms, group 1 received psychotherapy and group 2 did not, although it required it, for this reason it was considered the control. The psychotherapy consisted of 17 sessions and the used techniques most frequently were: confrontation, clarification and interpretation. RESULTS: Differences in the diminution as in the absence of symptoms were observed as much after the psychotherapeutic process. CONCLUSIONS: The psychoanalytic psychotherapy is functional in this type of patients for the diminution and in some cases the disappearance of psychological symptoms. PMID- 17849810 TI - [Antiphospholipid syndrome and human reproduction]. AB - Recurrent pregnancy loss is secondary to multiple illnesses. An important cause sometimes undiagnosed is the antiphospholipid syndrome, an autoimmune disease with various clinical alterations (miscarriage, hypertensive disorders, preterm delivery, vascular thrombosis, intrauterine retard growth, death intrauterine, abruption placentae). There are major and minor clinical criteria and precise indications that guide the physician to its recognition. Antibodies related with the syndrome are anticardiolipin and lupic anticoagulant, but other phospholipids seems to be implicated on this pathology and its participation on trombotic events is even unknown. Opportune diagnosis is of vital importance for fetomaternal morbidity and mortality. The repercussions are important during gestational stage, but effects c an persist o r even appear during the puerperium, predisposing t o trombotic events. The antiphospholipid s yndrome th at accompanies gestation, requires of efficient valuation and a special treatment, with a narrow prenatal surveillance. The best therapy for reproductive future which has less undesirable effects, is with heparin and acetylsalicylic acid administration; prednisone (steroids) is used in cases of active illness. The current knowledge about this disease makes possible that a pregnancy at term can be achieved with the least as possible number of complications. PMID- 17849811 TI - [Cardiovascular disease as a current threat of older women. Relation to estrogens]. AB - Cardiovascular disease (CVD) is the leading cause of death in women around the world. Cardiovascular disease risk increases after the menopause which may be related to metabolic and hormonal changes. The decline in ovarian function with menopause is associated with spontaneous increases in proinflammatory cytokines. Chronic inflammation is a major factor that drives the progression of atherosclerosis and atherothrombosis. Measurement of the inflammatory markers has been postulated as a method of determining increased risk of cardiovascular disease in apparently healthy older women. Endogenous estrogen appears to be cardioprotective and several observational epidemiological studies have suggested that hormone therapy reduces the risk of coronary events in healthy postmenopausal women. However, recent clinical studies failed to show such beneficial effect. Among the mechanism that may account for the effects of hormone therapy on cardiovascular disease is inflammation. PMID- 17849812 TI - [Contemporaneous history: complex techniques of assisted reproduction]. AB - The work begins with historical considerations about the development of embryology at the beginning of the twentieth century and the vast advance obtained to the arriving of complex assisted reproductive techniques. Afterwards it is reviewed the development of variants and possibilities of the techniques. Finally, it is proposed four historic periods regarding the development of complex assisted reproductive technologies. PMID- 17849813 TI - ["Memory note" on Dr. Mario Lopez Llera]. PMID- 17849814 TI - [Clinical assessment of ectopic pregnancy. 1952]. PMID- 17849815 TI - "Medicover": a proposal for national health insurance. PMID- 17849816 TI - Preventing under-equipped medical facilities from killing heart attack patients: correcting inefficiencies in the current regulatory paradigm for providing critical health care services to patients with acute coronary syndrome. PMID- 17849817 TI - Should it be illicit to solicit? A legal analysis of policy options to regulate solicitation of organs for transplant. PMID- 17849818 TI - Familial consent for registered organ donors: a legally rejected concept. PMID- 17849819 TI - Improper bedside manner: why state partner notification laws are ineffective in controlling the proliferation of HIV. PMID- 17849820 TI - State v. Physicians et al.: legal standards guiding the mature minor doctrine and the bioethical judgment of pediatricians in life-sustaining medical treatment. PMID- 17849821 TI - Pulmonary function prediction equations of male gold miners in Ghana. AB - OBJECTIVES: To determine the reference values and prediction equations for the Ghanaian gold miner and to compare the lung function indices with those working in other parts of Africa. DESIGN: Descriptive study of the lung functions of life long non smoking underground gold miners Prediction equations and reference values were then derives from best fitting equations and compared with previously published reference equations. SETTING: The study was conducted at the Obuasi gold mini in Ghana. SUBJECTS: Tests were conducted on 1 210 male miners. MAIN OUTCOME MEASURE: To assess the lung functions of the Ghanaian gold miner. RESULTS: The estimated prediction equations were as follows FVC (1) = -4.068 to 0.0210 x age (y) + 0496 x height (cm); FEV1(1) = -2.555 to 0.0210 age (y) +0.0360 x height (cm) and FET(25-75%) = -0.515 to 0.0157 x age (y)+ 0.0249 x height(cm). The closest fitting reference value was that of the European Community for Steel and Coal (ECCS) with a conversion factor (CF) of 0.87. CONCLUSION: The lung function indices of the Ghanaian gold miners are similar to those obtained from other west African countries, but lower than those from the southern and eastern Africa countries. The ECCS equation with a conversion factor of 0.87 fitted best for Ghanaian gold miners. Exposure to gold mine dust did not influence lung functions in this study. PMID- 17849822 TI - Stigma and discrimination: coping behaviours of people living with HIV and AIDS in an urban community of Mabvuku and Tafara, Harare, Zimbabwe. AB - OBJECTIVES: To assess how people living with HIV and AIDS reacted to the knowledge of the infection and how they are coping with stigma and discrimination. SETTINGS: The study was conducted in the two high density urban suburbs of Mabvuku and Tafara in Harare, Zimbabwe. DESIGN: The study was a descriptive cross sectional survey. SUBJECTS: A total of 600 participants (160 men and 440 women) who had received their HIV results after Voluntary Counselling and Testing for HIV at the Zimbabwe AIDS Prevention and Support Organization (ZAPSO) Mabvuku/Tafara Voluntary Counselling and Testing Centre were interviewed. MAIN OUTCOME MEASURES: Reactions to the diagnosis of HIV, disclosure of sero status, experiences of self, family and community induced stigma and discrimination, coping mechanisms and desired interventions to reduce stigma. RESULTS: The majority, 61.7%, had been diagnosed HIV positive less than two years at the time of the study. While 33.3% felt hurt, 41% were immediately depressed when they discovered they were HIV positive. Eighty five percent had not disclosed their sero-status to anyone. While 55% experience self induced stigma, 56.7% experienced family induced and 38.3% experienced community induced stigma. People living with HIV and AIDS were coping with stigma through withdrawal (60%); joining support groups (83.3%); seeking counselling (95%) and praying (86.7%). Encouraging community counselling and HIV testing with disclosure of status was perceived by 98.3% of the respondents as an effective method to reduce HIV and AIDS related stigma and discrimination. CONCLUSION: While non disclosure of sero status is still high, self, family and community induced stigma pose a big challenge. Withdrawal (used mostly by men), seeking counselling and joining support groups (used mostly by older women) are the common coping behaviours being used by HIV positive clients. There is need to improve counselling capacities so as to meet the demands from a stigma reduction perspective as well as from a coping perspective. PMID- 17849823 TI - Attitude of rural Nigerian pregnant women to antenatal HIV screening. AB - OBJECTIVE: To assess the knowledge and attitude of rural Nigerian women to the incorporation of HIV screening as part of the routine antenatal screening test at booking. METHODS: 1 820 women were interviewed using a close ended questionnaire at the antenatal clinic of the Federal Medical Centre (FMC) Owo, Nigeria over a period of 12 months. RESULTS: Though the majority of the women were of low socio economic status (85.9%) with 20% having less than six years of formal education, 98.6% of them were aware and knowledgeable (89.1%) about HIV/AIDS. The majority (89.9%) of the women accept routine HIV screening as part of antenatal screening. CONCLUSION: Based on the above findings, obstericians practicing in this locality are encouraged to incorporate HIV screening into their antenatal care. PMID- 17849824 TI - How are condoms used in a family planning setting: evidence from Zimbabwe. AB - OBJECTIVES: (To determine the level and consistency of condom use among family planning clients at three family planning clinics in Zimbabwe.) DESIGN: A prospective cross sectional study. SETTING: The study was carried out at three Zimbabwe National Family Planning Council clinics. SUBJECTS: We interviewed 899 consecutive women seeking family planning services at these three clinics using a structured questionnaire. MAIN OUTCOME MEASURES: The prevalence of condom use among this population of family planning clients and the factors predicting condom use were the main outcome measures. We define dual method use (DMU) as the use of condoms in conjunction with another highly effective contraceptive and dual purpose use (DPU) as the use of condoms for both pregnancy and STI/HIV prevention. We measured self-reported condom use during the last 30 days prior to each interview. RESULTS: The prevalence of condom use among this population of family planning clients was 38%. Of all the study participants, 32% were DMU clients while 5% were DPU clients. Fifty eight percent of the DMU clients and 89% of the DPU clients clients reported consistent condom use respectively. Logistic regression analysis showed that young age and reporting high risk sexual behaviour were predictors of condom use. CONCLUSIONS: The level of condom use among this population of family plannig clients is too low for a country with such a high HIV prevalence. Condom users were more likely to report DMU than DPU. Those reporting DPU were more likely to report consistent condom use. PMID- 17849825 TI - Pathogenesis of hyperparahyroidism in renal osteodystrophy. PMID- 17849826 TI - 401(k) plan asset allocation, account balances, and loan activity in 2006. PMID- 17849827 TI - Beyond the anti-kickback statute: new entities, new theories in healthcare fraud prosecutions. AB - The authors analyze existing and developing trends in healthcare fraud litigation. They first review the traditional use of the Medicare-Medicaid Anti Kickback Statute to prosecute such fraudulent activity. They then consider newer theories that have been employed, or may be employed, in cases involving payors, middlemen, agents, and fiduciaries. These include the use of the Civil False Claims Act, the Federal Travel Act, and the Public Contracts Anti-Kickback (sometimes incorporating violations under state commercial bribery and similar state legislation to form the basis of a federal claim or prosecution). The Article then turns to a discussion and warning of attorneys' potential liability for a client's kickback arrangements. Finally, the Article takes a very brief look at relationships under Medicare Part D that may well prove to be a fertile area of problematic conduct, public and congressional scrutiny, and prosecutions utilizing some of these theories. PMID- 17849828 TI - Prescription or proscription? The general failure of attempts to litigate and legislate against PBMS as "fiduciaries," and the role of market forces allowing PBMS to contain private-sector prescription drug prices. AB - Pharmacy benefit managers (PBMs), which generally administer prescription drug benefits as one component of an employer's or other sponsor's health insurance plan, have come under fire in recent years for turning profits at a time when consumer advocates and employers are struggling to contain the costs of health insurance and prescription drugs. Lawsuits alleging that PBMs are breaching certain fiduciary duties to the health plans they serve, however, have failed for the most part on grounds that PBMs are not "fiduciaries" under the Employee Retirement Income Security Act (ERISA). Moreover, states' attempts to regulate PBMs through legislation imposing fiduciary obligations and other related requirements have also generally failed for many different reasons. This Article examines the PBM industry, recent legal developments concerning PBMs' status as ERISA "fiduciaries", the arguments being made for and against stricter regulation of PBMs' business practices, and why litigation and legislation attempting to impose fiduciary obligations upon PBMs have generally failed. The authors conclude that it is market forces and competition, rather than litigation or legislation, that will effectively motivate PBMs to play a role in the cost containment of prescription drugs in the years ahead. PMID- 17849829 TI - Pharma on the hot seat. AB - The pharmaceutical industry has been receiving greater scrutiny lately due in large part to the many public and private legal enforcement actions taken against pharmaceutical manufacturers. These enforcement actions, along with legal developments such as the OIG Compliance Guidance for Pharmaceutical Manufacturers, the Sarbanes-Oxley Act's statutory guidelines for public corporations, the HIPAA privacy regulations, and the Medicare Modernization Act, have the potential to encourage the pharmaceutical industry to self-regulate beyond the bounds currently required by the law. After a brief overview of enforcement actions and compliance programs directed toward the pharmaceutical industry, this Article reviews a similar situation the hospital industry faced when Medicare promulgated major reimbursement modifications. The Article proposes that the pharmaceutical industry, in the face of such intense scrutiny and uncertainty, should implement more rigorous self-regulation. Without more stringent self-regulation, this intense interest in the pharmaceutical industry may result in a regulatory push that establishes unanticipated and cumbersome measures for the industry. PMID- 17849830 TI - Caracci and the valuation of exempt organizations. AB - In Caracci v. Commissioner, the Internal Revenue Service faced an important test in its application of Excess Benefit Taxes to disqualified persons of a nonprofit corporation that converted to for-profit status. This Article, written by the taxpayers' valuation expert, details the difficulties in the IRS case and demonstrates the reasons for the Fifth Circuit's reversal of the Tax Court's judgment in favor of the IRS. The author concludes with a number of lessons that taxpayers can take from Caracci. PMID- 17849831 TI - Seven years until electronic health records: the negative effects of the new Stark exceptions and anti-kickback safe harbors. AB - Last year's introduction of an exception to the Stark Regulations and a new Anti Kickback safe harbor allows donors (mainly hospitals) to assist recipients (mainly physicians) with the establishment of electronic health records systems. This Article analyses the new regulations and makes the case that, among other negative effects, they will create an undesirable shift in physician referrals in the short term. PMID- 17849832 TI - Survey of local public health workers' perceptions toward responding to an influenza pandemic. AB - BACKGROUND: Current national preparedness plans require local health departments to play an integral role in responding to an influenza pandemic, a major public health threat that the World Health Organization has described as "inevitable and possibly imminent". To understand local public health workers' perceptions toward pandemic influenza response, we surveyed 308 employees at three health departments in Maryland from March - July 2005, on factors that may influence their ability and willingness to report to duty in such an event. RESULTS: The data suggest that nearly half of the local health department workers are likely not to report to duty during a pandemic. The stated likelihood of reporting to duty was significantly greater for clinical (Multvariate OR: 2.5; CI 1.3-4.7) than technical and support staff, and perception of the importance of one's role in the agency's overall response was the single most influential factor associated with willingness to report (Multivariate OR: 9.5; CI 4.6-19.9). CONCLUSIONS: The perceived risk among public health workers was shown to be associated with several factors peripheral to the actual hazard of this event. These risk perception modifiers and the knowledge gaps identified serve as barriers to pandemic influenza response and must be specifically addressed to enable effective local public health response to this significant threat. (See chart at end of article). PMID- 17849833 TI - Use of force in private security: a primer. AB - The need for private security to provide an effective response to physical threats has become more important, according to the author. Both the security director and administrator, he states, must determine an effective policy in advance. The article outlines such a use of force policy as well as discussing other considerations that are involved in carrying it out. PMID- 17849834 TI - A model response to combative patient behavior. AB - This article discusses a relatively simple behavioral model that can be used by hospital staff to understand the actions of potentially combative patients. The model can be used, the author says, as a common guideline for the actions of staff members responding to potentially assaultive behavior by patients. PMID- 17849835 TI - Unique emergency training for healthcare safety/security officers. AB - The need for emergency preparedness and other training courses for healthcare safety/security staffs is being met by the American Red Cross, according to the author, who describes in detail what training is available from local chapters of that organization. PMID- 17849836 TI - Suicide bombers: are you a target? What can you do? AB - Since 9/11 the way major disasters are analyzed and prepared for has taken a new slant. Terrorism and its affect on the health care environment, according to the author, is an always-present factor in disaster planning. This article addresses some of the characteristics of suicide bombers, their possible motivations and behavior indicators in an effort to provide more tools to reduce the likelihood of a suicide bomb event affecting your facility. PMID- 17849837 TI - Encouraging staff involvement in the security effort. AB - Developing greater rapport between the security department and other hospital employees is essential to a successful security effort. In this article, the author describes a number of methods which can be used to better integrate the security program into the culture of the hospital. PMID- 17849838 TI - Diversity in action; dealing with a transgender issue. AB - The problem of gays in the military, police, and security has received considerable publicity in recent years, but what happens when a male security officer, with an excellent performance record, decides to announce a gender change? How a hospital's security and resources departments handled the transition, and what transpired afterwards, is described in this detailed and frank article. PMID- 17849839 TI - Obtaining CHPA certification: was it worth it? AB - Required to achieve CHPA certification late in his career, the author relates his doubts about undertaking the challenge, his stress in studying for and taking the exam, and the new challenges he is facing after passing it. PMID- 17849840 TI - Strategic security management: risk assessments in the environment of care. AB - Securing the environment of care is a challenging and continuous effort for most healthcare security managers, who face unique challenges in balancing the open campus environment with the protection needs of the hospital's patients, employees, and other assets. By conducting a comprehensive risk assessment, hospital security managers can prioritize identified risks, develop an effective hospital security program, and reduce risk to a manageable and acceptable level. This article discusses a 5-step risk assessment process that enhances the hospital security program by effectively mitigating risks to the hospital. PMID- 17849841 TI - Access management: will raising the drawbridge keep your healthcare facility safe? AB - A Campus Access Management Plan that enables a hospital facility to better survive a disaster is described by the author. The plan, which has been developed by a number of neighboring healthcare facilities, recognizes that since potential disasters will be community based, a community-wide approach to disaster survival is called for. PMID- 17849842 TI - Taking a strategic approach to campus parking. AB - Building a new parking facility in a campus setting - such as a hospital or medical center - is not an easy assignment. By taking a strategic planning approach, according to the author, campus planners can meet the needs of most of their constituents for convenient, easily accessible and safe parking. PMID- 17849843 TI - Controlled chaos: managing your access control system for future success. AB - How a medical center's protective services department is keeping pace with and planning for future changes in the face of unprecedented rapid growth. PMID- 17849844 TI - Designing a hospital-wide crime prevention program. AB - The article is designed as a generic guide and checklist to assist hospital security departments in defining the roles and responsibilities of departments, managers and personnel in preventing crime. PMID- 17849845 TI - Understanding the role of the security design consultant. AB - As the employment of new and more complicated devices to meet security needs has grown, so has the need for special expertise in this area. The role of the security design consultant and the advantages of utilizing such services are explained by the author. PMID- 17849846 TI - Putting vendors to the test. AB - Replacing or upgrading security systems requires that all parties involved acceptably test each component of the system before the system is turned over to the owner. This process, called commissioning, according to the authors, has enabled their hospital to preempt problems that could otherwise have plagued new systems after installation. PMID- 17849847 TI - Incorporating ecologically relevant measures of pesticide effect for estimating the compatibility of pesticides and biocontrol agents. AB - The compatibility of biological control agents with pesticides is a central concern in integrated pest management programs. The most common assessments of compatibility consist of simple comparisons of acute toxicity among pest species and select biocontrol agents. A more sophisticated approach, developed by the International Organisation of Biological Control (IOBC), is based on a tiered hierarchy made up of threshold values for mortality and sublethal effects that is used to determine the compatibility of pesticides and biological control agents. However, this method is unable to capture longer term population dynamics, which is often critical to the success of biological control and pest suppression. In this article, we used the delay in population growth index, a measure of population recovery, to investigate the potential impacts that the threshold values for levels of lethal and sublethal effects developed by the IOBC had on three biocontrol agents: sevenspotted lady beetle, Coccinella septempunctata L.; the aphid parasitoid Diaeretiella rapae (M'Intosh), and Fopius arisanus (Sonan), a parasitoid of tephritid flies. Based on life histories of these economically important natural enemies, we established a delay of 1-generation time interval as sufficient to disrupt biological control success. We found that delays equivalent to 1-generation time interval were caused by mortality as low as 50% or reductions of offspring as low as 58%, both values in line with thresholds developed by the IOBC. However, combinations of mortality and reduction of offspring lower than these values (from 32 to 43% each) over a simulated 4-mo period caused significant population delays. Furthermore, the species used in these simulations reacted differently to the same levels of effect. The parasitoid D. rapae was the most susceptible species, followed by F. arisanus and C. septempunctata. Our results indicate that it is not possible to generalize about potential long-term impacts of pesticides on biocontrol agents because susceptibility is influenced by differences in life history variables. Additionally, populations of biocontrol agents may undergo significant damage when mortality approaches 50% or when there is mortality of -30% and a 30% reduction in offspring caused by a sublethal effect. Our results suggest that more ecologically relevant measures of effect such as delays in population growth may advance our knowledge of pesticide impacts on populations of beneficial species. PMID- 17849849 TI - Colony dynamics of the Formosan subterranean termite in a frequently disturbed urban landscape. AB - The success of evaluating areawide control of the Formosan subterranean termite, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae), in urban landscapes hinges on detailed understanding of colony movement and plasticity of the breeding system. Most previous studies of colony affiliation and breeding systems of C. formosanus have been conducted in relatively undisturbed park-like areas. However, disturbance in the form of landscaping, construction, and nearby treatment may impact termite colony dynamics in urban habitats. Therefore, we used microsatellite genotyping to identify the number of colonies, assess colony movement, and investigate the breeding structure of colonies surrounding the Supreme Court Building in New Orleans, LA. During 4 yr, 18 distinct colonies were identified in the study area. In contrast to earlier studies in park-like areas, which indicated stable foraging areas, colonies in this study moved frequently into and out of inground stations. Five colonies were simple families; two of these colonies were headed by inbred nestmate pairs, and three of these colonies were headed by outbred unrelated pairs. Thirteen colonies were extended families headed by fewer than five neotenic reproductives. During the study, the predominant breeding system shifted; simple family colonies either moved or were eliminated, and they were replaced with new extended family colonies. In one case, a generation turnover within a colony from simple to extended family was observed. PMID- 17849848 TI - Species-diagnostic single-nucleotide polymorphism and sequence-tagged site markers for the parasitic wasp genus Nasonia (Hymenoptera: Pteromalidae). AB - Wasps of the genus Nasonia are important biological control agents of house flies and related filth flies, which are major vectors of human pathogens. Species of Nasonia (Hymenoptera: Pteromalidae) are not easily differentiated from one another by morphological characters, and molecular markers for their reliable identification have been missing so far. Here, we report eight single-nucleotide polymorphism and three sequence-tagged site markers derived from expressed sequenced tag libraries for the two closely related and regionally sympatric species N. giraulti and N. vitripennis. We studied variation of these markers in natural populations of the two species, and we mapped them in the Nasonia genome. The markers are species-diagnostic and evenly spread over all five chromosomes. They are ideal for rapid species identification and hybrid recognition, and they can be used to map economically relevant quantitative trait loci in the Nasonia genome. PMID- 17849850 TI - Role of Myzus persicae (Hemiptera: Aphididae) and its secondary hosts in plum pox virus propagation. AB - Plum pox virus (family Potyviridae, genus Potyvirus, PPV) is one of the most important viral pathogens of plants in the genus Prunus, particularly Prunus persica L. The role of the Myzus persicae (Sulzer) (Hemiptera: Aphididae) as a vector of PPV-M, and its role in spreading PPV-M, was investigated. PPV-M infected peach trees were used as inoculum sources, and transmission to 15 herbaceous species commonly present in and around peach orchards was evaluated. The presence of PPV-M in secondary hosts after aphid transmission was verified by reverse transcription-polymerase chain reaction tests. The results indicate that Saponaria ocymoides L., Pisum sativum L., Trifolium repens L., Trifolium pratense L., Lepidium sativum L., Matricaria chamomilla L., Centaurea cyanus L., Bellis perennis L., Papaver rhoeas L., and Zinnia elegans L. became infected. Although Lupinus polyphyllus Lindley, Taraxacum officinale L., Achillea millefolium L., Amaranthus retroflexus L., and Linum rubrum L. did not become infected, they are hosts of M. persicae. Among the 10 positive species that were infected, the species most common in peach orchards, T. pratense, T. repens, B. perennis, and M. chamomilla, were used as source plants for the transmission studies to the peach tree. Our study reveals the ability of M. persicae to transmit PPV-M from herbaceous hosts to peach trees, describes PPV-M symptoms in herbaceous species, and discusses the role of M. persicae and its hosts as a source of PPV-M in peach orchards. PMID- 17849851 TI - Toxicity of seven foliar insecticides to four insect parasitoids attacking citrus and cotton pests. AB - Laboratory studies were carried out to compare the toxicity of seven foliar insecticides to four species of adult beneficial insects representing two families of Hymenoptera: Aphelinidae (Aphytis melinus Debach, Eretmocerus eremicus Rose & Zolnerowich, and Encarsiaformosa Gahan) and Mymaridae (Gonatocerus ashmeadi Girault) that attack California red scale, Aonidiella aurantii (Maskell); sweetpotato whitefly, Bemisia tabaci (Gennadius) (both E. eremicus and E. formosa); and glassy-winged sharpshooter, Homalodisca vitripennis (Germar), respectively. Insecticides from four pesticide classes were evaluated using a petri dish bioassay technique across a range of concentrations to develop dosage-mortality regressions. Insecticides tested included acetamiprid (neonicotinoid); chlorpyrifos (organophosphate); bifenthrin, cyfluthrin, and fenpropathrin (pyrethroids); and buprofezin and pyriproxyfen (insect growth regulators [IGRs]). Chlorpyrifos was consistently the most toxic pesticide to all four species of beneficial insects tested based on LC50 values recorded 24 h posttreatment compared with 48-h LC50 values with the neonicotinoid and pyrethroids or 96 h with the IGRs. Among the three pyrethroids, fenpropathrin was usually less toxic (except similar toxicity to A. melinus) than was cyfluthrin, and it was normally less toxic (except similar toxicity with E. formosa) than was bifenthrin. Acetamiprid was generally less toxic than bifenthrin (except similar toxicity with G. ashmeadi). The IGRs buprofezin and pyriproxyfen were usually less toxic than the contact pesticides, but we did not test for possible impacts on female fecundity. For all seven pesticides tested, A. melinus was the most susceptible parasitoid of the four test species. The data presented here will provide pest managers with specific information on the compatibility of select insecticides with natural enemies attacking citrus and cotton, Gossypium hirsutum L., pests. PMID- 17849852 TI - Development of a meridic diet for Hylobius transversovittatus (Coleoptera: Curculionidae) and the role of carbohydrates in feeding, growth, and survival of larvae. AB - The root-feeding weevil Hylobius transversovittatus Goeze (Coleoptera: Curculionidae) is used for biological control of the invasive plant purple loosestrife, Luthrum salicaria L. (Lythraceae). A simple rearing system for this weevil was developed with the goals of improving production techniques and increasing the availability of insects for field introduction. Additionally, the dietary effects of digestible and indigestible carbohydrates were explored. A meridic diet for rearing H. transversovittatus was formulated through nutritional alterations of a boll weevil, Anthonomus grandis grandis Boheman, diet. Diet attractiveness was evaluated on two levels: first, by recording the incidence of initial tunneling, and second, by estimating the larval establishment rate. The performance of test diet formulations was further assessed by measuring developmental and survival rates of H. transversovittatus. Sucrose, starch, and three types of indigestible carbohydrates were tested as components to improve diet performance. Physical properties of the diet, modified by fillers in test formulations, produced major effects on the initial tunneling of hatchlings. The establishment of hatchlings was affected by chemical properties of the diet. Increases in sucrose concentration decreased larval establishment, decreased the rate of larval development, and decreased larval survival. However, omitting sucrose from the diet, or replacing it with starch, increased mortality of first instars. In advanced stages of larval development, omitting sucrose from the diet did not significantly affect larval survival. The developmental rate of larvae was increased when the amount of digestible carbohydrate was reduced. To date, seven generations of the univoltine H. transversovittatus have been successfully produced on this new meridic diet. PMID- 17849853 TI - Enhanced efficacy of Beauveria bassiana for red flour beetle with reduced moisture. AB - Red flour beetle, Tribolium castaneum (Herbst), is a major pest of stored and processed grains that is tolerant of Beauveria bassiana (Balsamo) Vuillemin under most conditions. Laboratory assays demonstrated that desiccating conditions improved the efficacy of the fungus. For T. castaneum larvae exposed to B. bassiana at different vapor pressure deficits (VPDs), the LC50 potency ratios were 2.3 for 2.42 kPa and 3.9 for 3.31 kPa compared with 1.06 kPa. There were significant effects of moisture on B. bassiana-associated mortality even with brief exposure to low VPD before or at the beginning of exposure to fungus. When T. castaneum larvae were held at 3.31 kPa 1 d before exposure to B. bassiana and/or in the first 1 or 2 d of exposure to the fungus, there was significantly greater mortality for all of the low moisture treatments than occurred with continuous incubation at 1.06 kPa. B. bassiana efficacy for adult T. castaneum was significantly better for VPDs of 3.56 or 3.78 than 1.06 kPa. Weight gain over 4 d of incubation with moisture held constant was significantly less at a VDP of 3.31 kPa than at 1.87 or 1.06 kPa. Treatment with fungus did not affect weight gain significantly. There was no significant difference in larval water content among treatments. PMID- 17849854 TI - Enhancement of nucleopolyhedrovirus infectivity against Mamestra brassicae (Lepidoptera: Noctuidae) by proteins derived from granulovirus and a fluorescent brightener. AB - The synergistic enhancement of nucleopolyhedrovirus (NPV) infection by granuloviruses (GVs) is well documented; and a GV granule protein, named viral enhancin, has been identified as an active contributor to this effect. We detected the presence of two proteins with molecular mass of 93 and 108 kDa in granules of a GV isolated from Xestia c-nigrum (L.) (XecnGV) as candidates for enhancin, and we confirmed that at least the 108-kDa protein enhances the infectivity of Mamestra brassicae nucleopolyhedrovirus (MabrNPV). We tested the effect of virion-free proteins obtained from XecnGV granules (GVPs) on MabrNPV infection, and we made a comparison with an enhancing chemical, the stilbene derived fluorescent brightener Tinopal. Bioassay was performed employing the diet contamination method, by using second instars of Mamestra brassicae (L.) (Lepidoptera: Noctuidae). The enhancing effects of GVPs (0.1 mg/g diet) and Tinopal (1 mg/g diet) were estimated to be 70.7-81.5-fold and 26.9-33.7-fold, respectively, as calculated from the LC50 values of MabrNPV with or without the additives. The additives reduced the lethal time of MabrNPV-infected larvae and they caused death at a younger instar. These results suggest that GVPs can enhance MabrNPV infection as effectively as Tinopal. PMID- 17849855 TI - Ethyl formate as a postharvest fumigant for selected pests of table grapes. AB - Ethyl formate (EF) in combination with CO2 was tested for control of arthropods commonly infesting California table grapes. In addition, table grape tolerance to EF exposure was evaluated. LC99 estimates were developed for target pests by using a range of EF concentrations (0.04-4.7% EF). Response to treatments varied greatly between species, as well as life stages within species. Western flower thrips, Frankliniella occidentalis (Pergande), and adult and crawler stages of grape mealybug, Pseudococcus maritimus (Ehrhorn), were most susceptible to EF treatments. Least susceptible were grape mealybug eggs; Pacific spider mite, Tetranychus pacificus McGregor; and omnivorous leafroller, Platynota stultana Walsingham. The LC99 for target pests fell within the range of EF concentrations tolerated by table grapes with the exception of 1-, 3-, and 5-d-old omnivorous leafroller pupae. PMID- 17849856 TI - Hot-water immersion quarantine treatment against Mediterranean fruit fly and Oriental fruit fly (Diptera: Tephritidae) eggs and larvae in litchi and longan fruit exported from Hawaii. AB - Immersion of litchi fruit in 49 degrees C water for 20 min followed by hydrocooling in ambient (24 +/- 4 degrees C) temperature water for 20 min was tested as a quarantine treatment against potential infestations of Mediterranean fruit fly, Ceratitis capitata (Wiedemann); and oriental fruit fly, Bactrocera dorsalis Hendel, eggs or larvae in Hawaiian litchi, Litchi chinensis Sonnerat. The 49 degrees C hot-water immersion of litchi provided probit 9 (99.9968% mortality with >95% confidence) quarantine security against eggs and first instars. There were no survivors from 15,000 each feeding and nonfeeding Mediterranean fruit fly or oriental fruit fly third instars immersed in a computer-controlled water bath that simulated the litchi seed-surface temperature profile during the 49 degrees C hot-water immersion treatment. Litchi served as the model for longan, Dimocarpus longan Lour., a closely related fruit that is smaller and also has commercial potential for Hawaii. Modified fruit infestation and holding techniques used to obtain adequate estimated treated populations from poor host fruit, such as litchi and longan, are described. Data from these experiments were used to obtain approval of a hot-water immersion quarantine treatment against fruit flies for litchi and longan exported from Hawaii to the U.S. mainland. PMID- 17849857 TI - Thermal requirement for development of Sancassania rodionovi (Acari: Acaridae) on mushrooms. AB - The free-living mite species Sancassania rodionovi (Zachvatkin) (Acari: Acaridae), is a serious pest of mushrooms in Iran. Studies were conducted to examine the development of this mite in relation to temperature on two mushroom species: Agaricus bisporus Lange (button mushroom) and Pleurotus ostreatus Kummer (oyster mushroom). The developmental time of this acarid mite was studied at eight constant temperatures, ranging from 5 to 40 degrees C, and developmental rates were modeled as a function of temperature. Sancassania rodionovi completed immature development in 17.35 +/- 0.58 and 20.17 +/- 0.88 d at 25 degrees C on button and oyster mushrooms, respectively. When the mite fed on button mushroom, the rate of development increased gradually from 10 to 35 degrees C. Using a linear model, the developmental zero was estimated to be 3.50 degrees C with a thermal constant of 357.14 degree-days. The Logan 10, Briere 1, and Thermodynamic models adequately described the data for this mite and yielded R2 values >0.95; these models provided estimates of optimum temperature for development of 33.244, 32.145, and 32.148 degrees C, respectively. Understanding the influence of temperature on development of S. rodionovi is discussed with respect to pest management in mushroom production. PMID- 17849858 TI - Population dynamics of a Western corn rootworm (Coleoptera: Chrysomelidae) variant in east central Illinois commercial maize and soybean fields. AB - Three on-farm sites in Iroquois County, IL, each containing an adjacent 16.2-ha commercial production maize, Zea mays L., and soybean, Glycine max (L.) Merr., field, were monitored for western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), adults from June through September 1999 2001. Mean captures of D. v. virgifera adults as measured with Pherocon AM yellow sticky traps were significantly greater in maize than in soybean. Overall mean numbers of D. v. virgifera adults captured with vial traps were significantly greater in soybean than in maize. Emergence cage data revealed that after 50% emergence of D. v. virgifera adults occurred, peak captures of D. v. virgifera adults occurred in maize as measured with vial and Pherocon AM traps. After maize reached the R2 (blister stage, 10-14 d after silking) stage of development and 90% emergence of D. v. virgifera adults had occurred, peak captures of D. v. virgifera adults were observed in soybean by using vial and Pherocon AM traps. Also, after maize reached the R2 stage of development, numbers of females significantly increased in soybean and decreased in maize. Captures of female D. v. virgifera adults frequently exceeded published economic thresholds in soybean, regardless of trap type used. Estimated survival of variant D. v. virgifera (egg to adult) in these commercial rotated maize fields was 10.7 and 9.4% from 1999 to 2000 and from 2000 to 2001, respectively. This compares with nonvariant D. v. virgifera survival estimates in continuous maize production systems in Iowa of 6.7 and 11% from 1983 to 1984 and from 1984 to 1985, respectively. PMID- 17849859 TI - Effect of age and mating status on adult European corn borer (Lepidoptera: Crambidae) dispersal from small-grain aggregation plots. AB - The European corn borer, Ostrinia nubilalis (Hubner) (Lepidoptera: Crambidae), is often controlled with genetically modified corn, Zea mays L., hybrids (Bacillus thuringiensis [Bt] corn) in the United States. If Bt-resistant insects are detected in the field, mitigation-remediation tactics must be implemented to sustain the efficacy of insecticidal, transgenic corn. Mass releasing laboratory reared, susceptible adults near aggregation sites to mate with locally emerging resistant adults is a possible remediation tactic, but it is imperative that the former remain in or near the release site long enough to mate. Understanding adult dispersal behavior relative to the timing of mating is important, because it directly affects patterns of gene flow and the rate at which Bt resistance moves through a population. Previous work shows that newly eclosed adults do not remain in proximity to their natal field. However, moth age, reproductive development, or mating status may influence the propensity to disperse. The objectives of this study were to determine the effect of adult age (0-3, 4-6, and 7-10 d old) and mating status on dispersal of adults released in small-grain aggregation plots. Less than 1% of the marked adults released in the aggregation plots remained after one night. More males than females were recovered. Age influenced dispersal, with mostly 4-6-d old adults being recovered. Conversely, mating status did not affect the number of adults recovered. Given the paucity of marked adult moths recovered near their release sites, mass releases of adults may not be a viable tactic to combat the spread of resistance to Bt corn. PMID- 17849860 TI - Field captures of wild melon fly (Diptera: Tephritidae) with an improved male attractant, raspberry ketone formate. AB - Field-trapping evaluations of the new male attractant, formic acid 4-(3-oxobutyl) phenyl ester (raspberry ketone formate [RKF]) were conducted in Hawaii with wild populations of melon flies, Bactrocera cucurbitae Coquillett (Diptera: Tephritidae), to determine its activity in the field and to evaluate new plastic matrix formulations. All tests were compared with the standard melon fly attractant 4-(4-acetoxyphenyl) -2-butanone (cuelure [CL]), which is the attractant of choice for detection programs aimed at melon fly and other cuelure responding Bactrocera fruit flies. Results of these tests over a range of doses on cotton wicks showed that at a 1-g dose raspberry ketone formate was 1.5-2 times more attractive compared with cuelure for up to 11 wk in the field. Lower doses applied on cotton wicks were less active, presumably due to hydrolysis of RKF to raspberry ketone. Raspberry ketone formate embedded in a plastic plug formulation also was field tested, and it was shown to be more attractive to male melon fly compared with cuelure. The use of this new attractant in control and detection programs is discussed. PMID- 17849861 TI - Influence of plant severing on movement of Ostrinia nubilalis larvae in Zea mays hybrid seed production fields. AB - Genetically engineered corn hybrids that contain a cry gene from the bacterium Bacillus thuringiensis Berliner (Bt) are gaining popularity for controlling the corn pest Ostrinia nubilalis (Hubner). Continuous use of Bt corn, however, could select for O. nubilalis that are resistant to this corn. Monitoring for insect resistance is important, because it could help maintain the Bt technology. A possible monitoring method is to collect larval insects in commercial drying bins after harvest from Bt seed production fields. A drawback to this method is that these collections may be contaminated by insects that moved as later instars from severed non-Bt male rows into the adjacent Bt female rows. These larvae have little to no exposure to Bt toxin, resulting in possible "false positives." The objectives of this study were to first find which combination of planting and severing dates produces the least number of larvae that move from non-Bt male plants to Bt female plants and to assess O. nubilalis larval movement from severed non-Bt male rows to Bt female rows. Field studies in 2002 and 2003 were designed to simulate a hybrid seed production field. Results suggest that movement of O. nubilalis larvae from male corn is minimized when corn is planted early and male plants are severed by 2 wk post-anthesis. This reduces the likelihood of false positives by reducing the number of susceptible larvae moving between Bt and non-Bt plants. Also, larvae moved to all four female rows that were adjacent to the severed rows, but there were significantly more larvae found in the closest row compared with the other three. These results could be used to develop a monitoring program to find O. nubilalis larvae with resistance to Bt corn in field populations of O. nubilalis. PMID- 17849862 TI - Distributions of lesser mealworm (Coleoptera: Tenebrionidae) in litter of a compacted earth floor broiler house in subtropical Queensland, Australia. AB - Distributions of lesser mealworm, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae), in litter of a compacted earth floor broiler house in southeastern Queensland, Australia, were studied over two flocks. Larvae were the predominant stage recorded. Significantly low densities occurred in open locations and under drinker cups where chickens had complete access, whereas high densities were found under feed pans and along house edges where chicken access was restricted. For each flock, lesser mealworm numbers increased at all locations over the first 14 d, especially under feed pans and along house edges, peaking at approximately 26 d and then declining over the final 28 d. A life stage profile per flock was devised that consisted of the following: beetles emerge from the earth floor at the beginning of each flock, and females lay eggs, producing larvae that peak in numbers at approximately 3 wk; after a further 3 to 4 wk, larvae leave litter to pupate in the earth floor, and beetles then emerge by the end of the flock time. Removing old litter from the brooder section at the end of a flock did not greatly reduce mealworm numbers over the subsequent flock, but it seemed to prevent numbers increasing, while an increase in numbers in the grow-out section was recorded after reusing litter. Areas under feed pans and along house edges accounted for 5% of the total house area, but approximately half the estimated total number of lesser mealworms in the broiler house occurred in these locations. The results of this study will be used to determine optimal deployment of site-specific treatments for lesser mealworm control. PMID- 17849863 TI - Comparison of two synthetic food-odor lures for captures of feral Mexican fruit flies (Diptera: Tephritidae) in Mexico and implications regarding use of irradiated flies to assess lure efficacy. AB - Feral Mexican fruit flies, Anastrepha ludens (Loew) (Diptera: Tephritidae), were trapped in a citrus orchard in Mexico by using two types of synthetic food-odor lures, the AFF lure (Anastrepha fruit fly lure, APTIV, Inc., Portland, OR) and the BioLure (two-component MFF lure, Suterra LLC, Inc., Bend, OR). In Multilure traps (Better World Manufacturing, Inc., Miami, FL) containing water, BioLures captured about the same numbers of flies as AFF lures. In Multilure traps containing antifreeze solution, BioLures captured 2 and 5 times more flies than AFF lures in two experiments. BioLures, and AFF lures did not differ in attractiveness when used on sticky traps (Intercept trap, APTIV, Inc.; and sticky cylinder trap). Multilure traps captured >4 times as many flies as sticky traps with the exception that captures of females did not differ between Multilure and sticky traps baited with AFF lures. The percentage of females captured in Multilure traps was greater when traps were baited with BioLures compared with AFF lures, but the reverse was true for sticky traps. Sticky cylinder traps captured a higher percentage of females than Multilure traps. The most effective trap/lure combination was the Multilure trap baited with BioLure and antifreeze. In comparison with tests of these two lures in Texas, results were similar for Multilure traps, but they differed for sticky cylinder traps in that AFF lures were consistently more attractive than BioLures in Texas, but not in Mexico. PMID- 17849864 TI - Irradiation of Anastrepha ludens (Diptera: Tephritidae) revisited: optimizing sterility induction. AB - Irradiation doses currently applied to sterilize Mexican fruit flies, Anastrepha ludens (Loew) (Diptera: Tephritidae), for release under the sterile insect technique eradication campaign in Mexico, were reviewed in an effort to increase sterile male performance in the field. A dose maximizing sterility induction into wild populations was sought by balancing somatic fitness with genetic sterility. Doses of 40, 60, and 80 Gy induced 95% or more sterility in all males, which in turn induced similar degrees of sterility into a cohort of wild flies in the laboratory. However, a low dose of 40 Gy was sufficient to completely suppress egg production in females. Similarly, a mild carryover of genetic damage might have been transferred to the F1 progeny of males irradiated at 40 Gy crossed with fertile wild females. Our results suggest that the 80-Gy dose currently applied in Mexico can be lowered substantially without jeopardizing program goals. This view could be strengthened by comparing performance of males irradiated at different doses under more natural settings. In general, we discuss the value of determining irradiation doses for pest species where females are more radiosensitive than males, by selecting the dose that causes 100% sterility in females. PMID- 17849865 TI - Within-plant distribution of Bemisia tabaci (Homoptera: Aleyrodidae) adults and immatures on greenhouse-grown winter cucumber plants. AB - Within-plant distribution of adults, pupae, nymphs, and eggs of Bemisia tabaci (Gennadius) (Homoptera: Aleyrodidae) on leaves of greenhouse-grown winter cucumber, Cucumis sativum L., plants were studied in field plots for integrated pest management decision making. Distribution of specific life stages depended on the leaf positions. The leaves with most abundance and low or lowest variation of whiteflies were leaves 8-12 for adults, 8-11 for pupae, 6-12 for nymphs, and 6-9 for eggs. In light of the criterion in selecting within-plant sample sites with pest abundance and low variation, these leaves were considered as the most convenient for sampling specific life stages of B. tabaci. Single a and b values for each life stage of the whitefly were calculated by Taylor's power law and were used to estimate minimum sample sizes at a precision of 0.25 (SE/mean). The minimum sample size decreased with increasing density of adults on leaves 8-12, of nymphs on leaves 7 and 8, and of eggs on leaf 6, but slightly increased with increasing density of pupae on leaves 8-11, of nymphs on leaves 6 and 9-12, and of eggs on leaves 7-9. PMID- 17849866 TI - Shifts in developmental diet breadth of Lymantria xylina (Lepidoptera: Lymantriidae). AB - The moth Lymantria xylina Swinhoe (1903) (Lepidoptera: Lymantriidae) is a major defoliator of hardwood and fruit trees in Taiwan. Although the plants identified as host plants of L. xylina usually refer to plants used as food or as shelter, most of the host plant identifications have not considered the role of these hosts on larval development. This study investigated various instars feeding on different plants to assess the developmental diet breath of L. xylina. Forty seven plant species, belonging to 25 families were used in feeding trials. Various bioassays, including first instar survival and long-term feeding trials, indicated the most suitable host plants for the different developmental stages. Results of the first instar survival trial indicated that first instars could survive only on 13 of the tested plant species. In addition, first instars could only successfully grow to pupa on seven of these 13 test plants species. To assess the developmental diet breath shifts of this moth, 38 plant species (excluding those nine plant species that the first instars did not feed upon) were fed to third and fifth instars in long-term feeding trials. Survival to pupa was noted on 12 and 13 test plant species for the third and fifth instars, respectively. In short, we found that the larvae performed differently when fed on various host plants and that the host plant range increased with the larval stage. Therefore, it is necessary to adjust the host plant range of this moth and to consider host plant breadth together with the developmental stages of caterpillars. PMID- 17849867 TI - Calling behavior of mass-reared and wild Anastrepha serpentina (Diptera: Tephritidae). AB - The calling behavior of mass-reared and wild males of Anastrepha serpentina (Wiedemann) (Diptera: Tephritidae) was studied both in the laboratory and in field cage tests. In the laboratory, density (1, 5, and 10 males per container), age, and hour of day significantly affected calling behavior. Mass-reared males called independently of density, whereas wild males only called at densities of 5 and 10 individuals. Males of both strains started calling when they were 5-7 d old. The daily pattern of male calling was similar in both strains, starting at 0730 hours, and reaching a peak at 1330-1630 hours. Field cage tests showed that mass-reared males started calling when they were 5d old; the period of peak calling was when males were 8-9 d old. In contrast, wild males began calling when they were 10 d old, reaching peaks when males were 13, 15, and 18 d old. Wild males tended to form leks to call during each day of the experiment, whereas mass reared males only formed leks during 2 d, both strains displaying very low levels. During field cage tests, males, independently of strain, displayed two calling peaks, one peak in the morning and one peak in the afternoon, whereas males observed in the laboratory only showed a single calling peak. The results are discussed in view of the effects of mass rearing A. serpentina males in relation to potential use of the sterile insect technique. PMID- 17849868 TI - Age-dependent variation in mating success of sterile male Mediterranean fruit flies (Diptera: Tephritidae): implications for sterile insect technique. AB - The sterile insect technique (SIT) is widely used in integrated programs against the Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae). Unfortunately, the mass-rearing procedures inherent to the SIT often lead to a reduction in the mating ability of the released males. To counter this deficiency, SIT programs rely upon the production and release of large numbers of sterile males to achieve high overflooding (sterile:wild male) ratios. To ensure a high release volume, emergence facilities release adult males at a young age (2 d old in some cases). The primary objective of this study was to describe age-dependent variation in the mating propensity and competitiveness of sterile males of C. capitata. Males that were 2 or 3 d old had lower mating propensity than males that were > or =4 d old, and 3-d-old males had lower mating competitiveness than males that were > or =4 d old. Given these results, we measured the effect of a longer holding period on male mortality in storage boxes. With delayed food placement, males held in storage boxes for 4 d after emergence showed no higher mortality than males held for only 2 d (the standard interval). Using large field enclosures, we compared the levels of egg sterility attained via releases of 2- versus 4-d-old sterile males at two overflooding ratios (5:1 and 100:1). At the lower ratio, the proportion of unhatched eggs observed for trials involving 2-d-old sterile males was not, on average, significantly higher than that observed for matings between wild flies (33 versus 25%, respectively), whereas the level of egg sterility observed for releases of 4 d old sterile males was 62%. At the 100:1 overflooding ratio, the proportion of unhatched eggs associated with the 2-d-old sterile males was 58%, a level not significantly different from that induced by 4-d-old sterile males at the 5:1 ratio and significantly lower than the level (79%) observed for 4-d-old sterile males at 100:1 overflooding ratio. The implications of these results for SIT are discussed. PMID- 17849869 TI - Changes in levels of juvenile hormone and molting hormone in larvae and adult females of Chilo suppressalis (Lepidoptera: Pyralidae) after imidacloprid applications to rice. AB - Insect hormones regulate growth and development and fecundity of insects. The current study investigated changes in juvenile hormone (JH) and molting hormone (MH) levels in fourth instars and adult females of Chilo suppressalis (Walker) (Lepidoptera: Pyralidae) after imidacloprid application to rice, Oryza sativa L. The results showed that JH level in fourth instars that developed feeding on Fengyouxiangzhan rice plants sprayed with 15, 30, and 60 ppm imidacloprid was significantly higher than that of larvae that developed on control plants, increasing by 5.04, 6.39, and 4.89 times, respectively. The relationships between JH level and imidacloprid concentrations showed a significant negative correlation. In contrast, molting hormone (MH) level in larvae fed on control plants was significantly higher than that on treated plants. JH:MH values in fourth instars developed from larvae feeding on rice plants treated with 15, 30, 60, 80, and 100 ppm imidacloprid increased by 49.17, 39.43, 13.48, 15.80, and 0.2 times, respectively, compared with control. JH and JH:MH ratio in larvae fed on Wujing 15 plants treated with imidacloprid were significantly lower than those fed on Fengyouxiangzhan under the same treatments. JH level in adult females that developed from larvae feeding on rice plants sprayed with imidacloprid significantly decreased with increase in imidacloprid concentration, but it increased compared with control. JH level in adult females was associated with times of imidacloprid application. JH level in adult females developed from larvae feeding on rice plants after double spray with 30 ppm imidacloprid was significantly higher than control, increasing by 61.6 and 116.5%, respectively, compared with a single spray and the control. Moreover, hormone levels in the larvae were related to the application method of imidacloprid. JH level in fourth instars after root application and topical application of imidacloprid was significantly lower than in control. Thus, the dynamics of JH and MH in insects after insecticide applications are an extremely interesting problem, because hormones are related to insect growth and development. PMID- 17849870 TI - Overwintering locations and hosts for onion thrips (Thysanoptera: Thripidae) in the onion cropping ecosystem in New York. AB - Identifying locations where onion thrips, Thrips tabaci Lindeman (Thysanoptera: Thripidae), overwinter and subsequently disperse is important for designing control strategies. In upstate New York from 2003 through 2006, potential overwintering sites in the commercial onion, Allium cepa L., cropping system were investigated early in the spring before onion seedling emergence and again late in the season after onions were harvested. Onion thrips adults were sampled directly from the soil and indirectly from the soil by using emergence cages. Sampling locations included onion field interiors and edges and areas outside of these fields, including woods. Host material sampled included onion culls; volunteer onions, which sprout from cull onions left behind after harvest; and weeds. Onion thrips adults were found in all sections of onion fields and in locations outside of onion fields, with the fewest emerging from woods. Emergence began in early May and extended into June. Peak emergence occurred during the last half of May, at which time 50-75% of the population had emerged. Adults colonized volunteer onions as early as late March and as late as mid-November. No adults were found overwintering in onion cull piles. Adults also colonized several weed species, especially pigweed, Amaranthus hybridis L., and lambsquarters, Chenopodium album L., late in the fall. Our results indicate that onion thrips adults overwinter in the soil within and near onion fields and that they probably colonize volunteer onion plants before subsequent generations infest the onion crop in the spring. Volunteer onions and weeds also provide onion thrips with a host after onions are harvested. Consequently, onion thrips management strategies should include tactics that reduce volunteer onion and weed abundance. PMID- 17849871 TI - Comparisons of ecorational and chemical insecticides against crucifer flea beetle (Coleoptera: Chrysomelidae) on canola. AB - Studies were done comparing the insecticides SpinTor (spinosad), BotaniGard (Beauveria bassiana), Neemix (azadirachtin), and Surround (kaolin, a clay) with conventional chemical insecticides Capture (bifenthrin) and Helix XTra (thiamethoxam), all applied at seven rates in a 7-d assay to assess their impact on adult crucifer flea beetle, Phyllotreta cruciferae (Goeze) (Coleoptera: Chrysomelidae). Lethal time (LT) required for 25, 50, and 75% mortality (LT25, LT50, and LT75) and relative potencies for the insecticide concentration groupings (0, 1X-1.5X, and 2X- 4X) were estimated for each treatment by using survival functions. P. cruciferae mortality increased in response to increasing concentrations, especially for Helix XTra, Capture and SpinTor. After 2 d of exposure in 2002, mortality ranged from 54 to 78% for Helix XTra, from 60 to 94% for Capture, and from 66 to 92% for SpinTor across concentrations. In 2003, flea beetle mortality ranged from 37 to 60%, from 29 to 63%, and from 23 to 52% on exposure to Helix XTra, Capture, and SpinTor, respectively, for 2 d. The LT50 and relative potencies of the insecticides were in the order of Helix XTra, Capture, and SpinTor > BotaniGard, Neemix, and Surround. In 2002, LT50 values were 1 and 2 d for Capture and SpinTor, 2 d for BotaniGard, and 3 d for Neemix and Surround. In 2003, LT50 values occurred between 2 and 4 d after exposure to Helix XTra, Capture, and SpinTor, with LT50 values of 5-7 d on exposure to BotaniGard, Neemix, and Surround. SpinTor seems to be a suitable ecorational insecticide in canola, Brassica napus L., for P. cruciferae management. PMID- 17849872 TI - Laboratory studies to elucidate the residual toxicity of eight insecticides to Anystis baccarum (Acari: Anystidae). AB - Anystis baccarum (L.) [=Anystis agilis (Banks)] (Acari: Anystidae) is a common predatory mite recently identified in apple (Malus spp.) orchards and in vineyards (Vitus spp.) in Quebec, Canada. Studies of its susceptibility to pesticides used in these crops need to be carried out to encourage integrated pest management programs. A laboratory evaluation of methoxyfenozide, acetamiprid, thiamethoxam, imidacloprid, spinosad, phosmet, carbaryl, and lambda cyhalothrin showed that residues of lambda-cyhalothrin, phosmet, and carbaryl were highly toxic in 48-h petri dish bioassays. The field rate of lambda cyhalothrin is 0.0184 g (AI) /liter, which is 26-fold the estimated LC50 of 0.0007 g (AI) /liter) for this predator. The field rate for phosmet is 0.6000 g (AI) /liter, which is 118-fold the LC50 for phosmet, which is 0.0051 g (AI) /liter), and the field rate for carbaryl is 1.960 g (AI) /liter, which is 784 fold the estimated LC50 of 0.0025 g (AI) /liter). Five other insecticides, methoxyfenozide, acetamiprid, thiamethoxam, imidacloprid, and spinosad, were evaluated and found to be nontoxic. PMID- 17849873 TI - Insecticidal activity of Citrus aurantium fruit, leaf, and shoot extracts against adult olive fruit flies (Diptera: Tephritidae). AB - Solvent extracts of differing polarity from Citrus aurantium (L.) (Rutaceae) fruit, leaves, and shoots were evaluated for biological activity against adults of the olive fruit fly, Bactrocera oleae (Gmelin) (Diptera: Tephritidae). Using a petri dish residual exposure bioassay, we found that the petroleum ether extract from fruit alone showed insecticidal activity against the flies. The extract of the three fruit tissues (flavedo [peel], albedo, and flesh) indicated that bioactivity was limited to the flavedo, and this activity was significantly higher than that of the whole fruit extract. The most effective extract was obtained when fresh flavedo was used, whereas extracts of oven-dried flavedo were inactive. Fruit maturity also affected bioactivity; extracts of ripe fruit were more effective than those of unripe fruit. Our results suggest that C. aurantium flavedo contains secondary metabolites with insecticidal activity against B. oleae adults. PMID- 17849874 TI - Feeding behavior and growth of corn earworm (Lepidoptera: noctuidae) larvae on Bacillus thuringiensis-treated (dipel 4L) and untreated meridic diet. AB - The effect of Dipel 4L in artificial diet on feeding behavior, occurrence on a specific diet, and growth of corn earworm, Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae), was assessed in short-term tests. Third-, fourth-, and fifth-stage laboratory-reared and feral corn earworm larvae were evaluated. Arenas used for each assay included a non-Dipel diet, Dipel-containing diet, and a combination of the two diets. Larval activity was observed immediately after exposure to diet and at 6 and 18 h for third instars and at 6, 8, and 24 h for fourth and fifth instars, respectively. Feral and laboratory-reared third, fourth, and feral fifth instars avoided Dipel-treated diet when more suitable food was available. Third and fourth instars consistently preferred non-Dipel-containing diet when presented a choice of foods. Corn earworm growth was delayed when larvae were subjected to Dipel-treated diet in choice and no-choice assays compared with larvae provided untreated diet. Larvae presented a choice of diets grew more rapidly than those presented Dipel-treated diets in no choice arenas. Larval feeding frequency and weight gain were superior when larvae were supplied untreated diet than when restricted solely to a Dipel-treated diet. Larvae presented a choice of diets spent more time feeding and fed more frequently on untreated diet than Dipel-treated food. These data indicate that corn earworm presented a choice of Bacillus thuringiensis (Bt) and non-Bt diets may have an increased probability of completing development compared with those restricted to Bt-laced sources. PMID- 17849875 TI - Threecornered alfalfa hopper (Hemiptera: Membracidae): seasonal occurrence, girdle distribution, and response to insecticide treatment on peanut in South Carolina. AB - A survey of threecornered alfalfa hopper, Spissistilus festinus (Say) (Hemiptera: Membracidae), damage in 60 South Carolina peanut, Arachis hypogaea L., fields showed that 89 and 58% of plants had feeding girdles during 2003 and 2004, respectively. Use of a foliar insecticide for other target pests reduced hopper damage. Hopper damage was not affected by sampling distance from the field edge; therefore, injury was adequately assessed at 10 m from field borders. In-furrow insecticide choice, planting date, soil texture, previous crop, or tillage did not measurably affect girdling. Subsequent field experiments demonstrated a cultivar effect on threecornered alfalfa hopper injury, with the standard runner type cultivar ('Georgia Green') more susceptible than the standard Virginia-type ('NC-V11'). More than 50% of stem girdling occurred on the basal quarter (first five internodes) of the plant. Most feeding occurred on secondary branches of main and lateral stems. Weekly sampling of seven grower fields showed that adult hoppers colonize peanut during June and produce two generations on peanut. Only low levels of plant girding were observed in June, but plant girdling increased gradually through late July, when girdling markedly increased contemporary with peak populations of first generation nymphs and adults. A second increase in plant girdling, observed in early September, coincided with the second generation of nymphs on peanut. Foliar treatments at 45- 60 d after planting (DAP) were most effective in suppressing injury. Granular chlorpyrifos treatment also suppressed hopper injury. There was no yield response to insecticide treatments at the hopper injury levels in these tests (up to six girdles per plant). Although the economic injury level (EIL) for this pest has not been defined, our data indicate that a critical interval for monitoring hopper activity is the first 3 wk of July, before the occurrence of significant injury. Where growers have a consistent risk of economic injury, applying foliar treatment in mid-July would be most effective in suppressing damage. PMID- 17849876 TI - Role of insecticides in reducing thrips injury to plants and incidence of tomato spotted wilt virus in Virginia market-type peanut. AB - Tomato spotted wilt virus (family Bunyaviridae, genus Tospovirus, TSWV), transmitted by many thrips species, is a devastating pathogen of peanut, Arachis hypogaea L. TSWV has become a serious problem in the Virginia/Carolina peanut growing region of the United States. During 2002, TSWV was present in 47% of the North Carolina hectarage and caused a 5% yield reduction in Virginia. Factors influencing levels of TSWV in runner market-type peanut cultivars, which are primarily grown in Alabama, Flordia, Georgia, and Texas, have been integrated into an advisory to help those peanut growers reduce losses. An advisory based on the southeast runner market-type version is currently under development for virginia market-type peanut cultivars that are grown primarily in the Virginia/ Carolina region. A version based on preliminary field experiments was released in 2003. One factor used in both advisories relates to insecticide use to reduce the vector populations and disease incidence. This research elucidated the influence of insecticides on thrips populations, thrips plant injury, incidence of TSWV, and pod yield in virginia market-type peanut. Eight field trials from 2003 to 2005 were conducted at two locations. In-furrow application of aldicarb and phorate resulted in significant levels of thrips control, significant reductions in thrips injury to seedlings, reduced incidence of TSWV, and significant increases in pod yield. Foliar application of acephate after aldicarb or phorate applied in the seed furrow further reduced thrips plant injury and incidence of TSWV and improved yield. These findings will be used to improve the current virginia market-type TSWV advisory. PMID- 17849877 TI - Impact of combining planting date and chemical control to reduce larval densities of stem-infesting pests of sunflower in the central plains. AB - The guild of stem-infesting insect pests of sunflower, Helianthus annuus L., within the central Plains is a concern to producers chiefly due to losses caused by plant lodging from the sunflower stem weevil, Cylindrocopturus adspersus (LeConte) (Coleoptera: Curculionidae), and Dectes texanus texanus LeConte (Coleoptera: Cerambycidae). The incidence of a root boring moth, Pelochrista womonana (Kearfott) (Lepidoptera: Tortricidae), also has increased. Experiments were conducted in three locations in Colorado and Kansas during 2001-2003 to investigate the potential of combining planting date and foliar and seed treatment insecticide applications to lower insect stalk densities of these three pests. The impact of these strategies on weevil larval parasitoids also was studied. Eight sunflower stem weevil larval parasitoid species were identified. All were Hymenoptera and included the following (relative composition in parentheses): Nealiolus curculionis (Fitch) (42.6%), Nealiolus collaris (Brues) (3.2%) (Braconidae), Quadrastichus ainsliei Gahan (4.2%) (Eulophidae), Eurytoma tylodermatis Ashmead (13.1%) (Eurytomidae), Neocatolaccus tylodermae (Ashmead) (33.7%), Chlorocytus sp. (1.6%), Pteromalus sp. (0.5%) (Pteromalidae), and Eupelmus sp. (1.0%) (Eupelmidae). The results from this 3-yr study revealed that chemical control was often reliable in protecting the sunflower crop from stem pests and was relatively insensitive to application timing. Although results in some cases were mixed, overall, delayed planting can be a reliable and effective management tool for growers in the central Plains to use in reducing stem infesting pest densities in sunflower stalks. Chemical control and planting date were compatible with natural mortality contributed by C. adspersus larval parasitoids. PMID- 17849878 TI - Economic threshold for soybean aphid (Hemiptera: Aphididae). AB - Soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), reached damaging levels in 2003 and 2005 in soybean, Glycine max (L.) Merrill, in most northern U.S. states and Canadian provinces, and it has become one of the most important pests of soybean throughout the North Central region. A common experimental protocol was adopted by participants in six states who provided data from 19 yield-loss experiments conducted over a 3-yr period. Population doubling times for field populations of soybean aphid averaged 6.8 d +/- 0.8 d (mean +/- SEM). The average economic threshold (ET) over all control costs, market values, and yield was 273 +/- 38 (mean +/- 95% confidence interval [CI], range 111-567) aphids per plant. This ET provides a 7-d lead time before aphid populations are expected to exceed the economic injury level (EIL) of 674 +/- 95 (mean +/- 95% CI, range 275-1,399) aphids per plant. Peak aphid density in 18 of the 19 location-years occurred during soybean growth stages R3 (beginning pod formation) to R5 (full size pod) with a single data set having aphid populations peaking at R6 (full size green seed). The ET developed here is strongly supported through soybean growth stage R5. Setting an ET at lower aphid densities increases the risk to producers by treating an aphid population that is growing too slowly to exceed the EIL in 7 d, eliminates generalist predators, and exposes a larger portion of the soybean aphid population to selection by insecticides, which could lead to development of insecticide resistance. PMID- 17849879 TI - Population dynamics of soybean aphid and biotic mortality at the edge of its range. AB - The soybean aphid, Aphis glycines Matsumura, was introduced to north central North America from Asia in 2000, and it has become a major pest of soybean, Glycine max (L.) Merr. Understanding how natural enemies impact aphid populations in the field is an important component in developing a comprehensive management plan. We examined the impact of naturally occurring predators in the field by using exclusion cages during July-August 2004 and 2005. Field cages of different mesh diameters were used to exclude different sizes of natural enemies from aphid infested plots. Plots were surveyed twice weekly for A. glycines and natural enemies. Densities were recorded. Cage effects on mean temperature and soybean growth were found to be insignificant. Significant differences in aphid density were found between treatments in both years of the study (2004 and 2005); however, aphid densities between years were highly variable. Orius insidiosus (Say) was the most commonly occurring predator in the field. Other natural enemies were present in both years but not in high numbers. Parasitoids were present in both years, but their numbers did not suppress aphid densities. Treatment differences within years were related to the abundance of natural enemies. The large differences in aphid abundance between years were associated with the higher number of O. insidiosus found in the field in 2005 (416 total O. insidiosus) than in 2004 (149 total O. insidiosus). This study suggests that naturally occurring predators, primarily O. insidiosus, can have a large impact on A. glycines populations when predator populations are established before initial A. glycines colonization. PMID- 17849880 TI - Mating attraction by Stenotus rubrovittatus (Heteroptera: Miridae) females and its relationship to ovarian development. AB - Stenotus rubrovittatus (Matsumura) (Heteroptera: Miridae) causes brown or black marks on rice, Oryza sativa L., grains (pecky rice), and it is becoming of increasing importance in Japan. Attractiveness of adult females or males of S. rubrovittatus to conspecific individuals was examined in the field in 2003 and 2004. Unmated female-baited traps captured significantly more males than did the unmated male-baited traps. However, the numbers of females captured by female- or male-baited traps were low, and they were not significantly different from the numbers caught by the control traps. No nymphs were captured by any traps. In 2004, we examined the effects of age and mating experience on female attraction ability with the goal of understanding the role of reproductive development in the observed behavior. The daily number of males captured by young unmated female (3-d-old)-baited traps increased from the first day until the fourth day of experiments, and then capture started to decrease. The peak in the number of captured males corresponded to the preoviposition period. When we observed ovarian development of S. rubrovittatus females under 25 degrees C and a photoperiod of 16:8 (L:D) h, we found that vitellogenesis had already started in approximately 30-50% of 1-d-old individuals. By the fifth day after emergence, 50 70% of individuals had mature eggs. These results indicated that the attractiveness of females is the strongest when egg laying becomes possible. Therefore, S. rubrovittatus females attract males selectively for mating, and it is probable that females use a sex pheromone for the attraction. PMID- 17849881 TI - Most susceptible stage of rice panicle development to Oebalus pugnax (Hemiptera: Pentatomidae). AB - Oebalus pugnax (F.) (Hemiptera: Pentatomidae) damage to rice, Orya savita L., reduces rough and head rice yields, and grain quality. O. pugnax feeds on developing kernels, introducing pathogenic fungi and causing a discoloration of the grain known as "peck." The objective of this study was to determine the stage of rice panicle development most susceptible to O. pugnax attack. During 2005 and 2006, in greenhouse and field experiments, rice plants were caged at the boot stage and then infested with adult or nymphal O. pugnax. Plants were infested during one of three stages of panicle development: heading, milk, or soft dough. Insects were allowed to feed on the plants for the duration of each stage and then killed. After maturation, panicles were harvested, and grain was hulled and milled. Grain weight, percentage of pecky grain, and percentage of whole grain after milling were recorded. No differences were found in the weight of rough, brown, or milled rice infested with O. pugnax during different stages of panicle development. Number of filled grains per cage was not affected by O. pugnax, and number of empty grains per cage was affected in two of four experiments. Higher percentage of peck was found in grain from panicles infested during dough and milk than in grain from panicles infested during heading. Adult O. pugnax caused higher percentage of peck than nymphs in all stages of panicle development. An inverse relationship was found between percentage of peck and percentage of whole grain weight only in one of the experiments. PMID- 17849882 TI - Distribution and hosts of Callidiellum rufipenne (Coleoptera: Cerambycidae), an asian cedar borer established in the eastern United States. AB - The distribution and hosts of the exotic cedar-boring beetle, Callidiellum rufipenne (Motschulsky) (Coleoptera: Cerambycidae), were determined in five northeastern U.S. states by capturing adults on cedar trap logs and by rearing adults from various conifers. This beetle was detected in the coastal states of Massachusetts, Rhode Island, Connecticut, New York, and New Jersey. In these states, adults emerged from the live or dead wood of four genera and eight species of Cupressaceae; species of Pinaceae were not hosts. Through its entire range, C. rufipenne is reported to infest at least 14 species of Cupressaceae, four species of Pinaceae, and one species of Taxaceae; but, records of Pinaceae and possibly Taxaceae are suspect. Based on the number of adults that emerged from coniferous poles in a five-way choice test in the field, the infestation level was significantly greater in Chamaecyparis thyoides (L.) Britton, Sterns, and Poggenburg and Juniperus virginiana L. than in Pinus rigida Miller, Pinus strobus L., and Tsuga canadensis (L.) Carribre (last three species uninfested). In a second test of host preference in the wild, beetles infested four cupressaceous species, but not Abies balsamea (L.) Miller, Picea rubens Sargent, Pinus rigida, P. strobus, and Ts. canadensis in the Pinaceae. Infestation level was highest in Ch. thyoides, followed in decreasing order by Juniperus communis L., Thuja occidentalis L., and J. virginiana. In a comparison of live and dead J. virginiana, beetles developed to adults only in dead trees (36 beetles per tree). When trunk sections of Th. occidentalis with and without bark were offered to females in cages, beetles of the next generation emerged exclusively from wood with bark. In the Northeast, only species of Cupressaceae apparently are suitable hosts for C. rufipenne. Infestation of these species may be prevented or reduced by proper care of live plants and by debarking trees after harvesting. PMID- 17849883 TI - Acaricidal activity of Juglans regia leaf extracts on Tetranychus viennensis and Tetranychus cinnabarinus (Acari: Tetranychidae). AB - Leaf extracts of the walnut, Juglans regia L., were evaluated under laboratory conditions to determine their acaricidal activity on the mites Tetranychus cinnabarinus (Boisduval) and Tetranychus viennensis Zacher (Acari: Tetranychidae). Extracts had both contact and systemic toxicity to these mites. The four solvents tested for preparing crude extracts were petroleum ether, chloroform, ethyl acetate, and methanol. Methanol was the most efficient solvent, with an extraction rate from 17.06 + 0.80 to 20.27 +/- 0.28%. Petroleum ether was the least effective solvent, with extraction rates from 2.30 +/- 0.13 to 2.71 +/- 0.13%. However, the crude extracts with petroleum ether resulted in the highest mite mortality (79.04 +/- 0.52%) in a slide dip bioassay. Mites mortalities from the concentrated extracts prepared by chloroform, ethyl acetate, methanol, or distilled water were significantly lower than petroleum ether. The mean lethal concentrations (LC50) of the extracts from petroleum ether, chloroform, ethyl acetate, methanol, and distilled water to the two mite species were 0.73 +/- 0.04, 1.66 +/- 0.28, 4.96 +/- 0.35, 7.45 +/- 0.67, and 9.91 +/- 0.32 mg/ml, respectively. After liquid chromatography and thin-layer chromatography, the concentrated extracts of petroleum ether were separated into eight fractions and tested for acaricidal activity. Fraction 6 produced significantly higher mite mortality rates than the other groups, killing approximately 90% of both species. PMID- 17849884 TI - Effects of chipping, grinding, and heat on survival of emerald ash borer, Agrilus planipennis (Coleoptera: Buprestidae), in chips. AB - The emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), a phloem-feeding insect from Asia, was identified in 2002 as the cause of widespread ash (Fraxinus sp.) mortality in southeastern Michigan and Essex County, Ontario. Most larvae overwinter as nonfeeding prepupae in the outer sapwood or thick bark of large trees. In a series of studies, we evaluated effects of grinding, chipping, and heat treatment on survival of A. planipennis prepupae in ash material. Heavily infested ash bolts containing roughly 8,700 prepupae were processed by a horizontal grinder with either a 2.5- or 10-cm screen. There was no evidence of A. planipennis survival in chips processed with the 2.5-cm screen, but eight viable prepupae were recovered from chips processed with the 10-cm screen. We chiseled additional sentinel chips with prepupae from ash logs and buried 45 in each chip pile. In total, six prepupae in sentinel chips survived the winter, but we found no sign of adult A. planipennis emergence from the processed chips. Subsequently, we assessed prepupal survival in chips processed by a chipper or a horizontal grinder fit with 5-, 10-, or 12.7-cm screens. An estimated 1,565 A. planipennis prepupae were processed by each treatment. Chips from the chipper were shorter than chips from the grinder regardless of the screen size used. No live prepupae were found in chips produced by the chipper, but 21 viable prepupae were found in chips from the grinder. Infested wood and bark chips chiseled from logs were held in ovens at 25, 40, or 60 degrees C for 8, 24, or 48 h. Prepupal survival was consistently higher in wood chips than bark chips at 40 degrees C, whereas no prepupae survived exposure to 60 degrees C for eight or more hours. In a second study, prepupae in wood chips were exposed to 40, 45, 50, 55, or 60 degrees C for 20 or 120 min. Some prepupae survived 20 min of exposure to all temperatures. No prepupae survived exposure to 60 degrees C for 120 min, but 17% survived exposure to 55 degrees C for 120 min, suggesting that some fraction of the population may survive internationally recognized phytosanitary standards (ISPM-15) for treatment of wood packing material. PMID- 17849885 TI - Development and evaluation of an emulsified paraffin wax dispenser for season long mating disruption of Grapholita molesta in commercial peach orchards. AB - The University of California at Davis patented the use of emulsified wax to release pheromones for mating disruption. Advantages of these dispensers include low cost, self-adhesion, and biodegradation. We compared the efficacy and practicality of Confuse-OFM, a commercial emulsified wax formulation of oriental fruit moth, Grapiholita molesta (Busck), pheromone with those of Check-Mate OFM-F sprayable pheromone and Isomate-M 100 polyethylene tube dispensers in commercial peach (Prunus spp.) orchards. Efficacy was measured with male captures in pheromone-, virgin female-, and liquid attractant-baited bucket traps as well as by noting injury to shoots and fruit. Two applications of Confuse-OFM were as effective as two applications of CheckMate OFM-F and one application of Isomate-M 100. However, Confuse-OFM was tedious to apply and wasted pheromone with an initially high release rate. We developed a new emulsified wax formulation (Wax Dollops) that maintained release rates above a 5 mg/ha/h threshold twice as long as Confuse-OFM in the laboratory. Field trials confirmed that one application of 3-ml dollops (590 dollops per ha) provided season-long (approximately 15 wk) control equivalent to that of Isomate-M 100 and Confuse-OFM applied as described above. Several applicators were developed for Wax Dollops, including a pneumatic gun that shot dollops >2 m. However, the most efficient method for application was wiping dollops onto tree branches by using a flat-bladed spatula. This research was the basis for a new line of commercial pheromone pest control products equally effective to current commercial formulations but with advantages in cost and flexibility. PMID- 17849886 TI - Potential management strategies for the linden borer (Coleoptera: Cerambycidae) in urban landscapes and nurseries. AB - The linden borer, Saperda vestita Say (Coleoptera: Cerambycidae), is a native insect species that is common throughout north central and northeastern North America. Over the past decade, increasing occurrence of damage associated with the linden borer has been reported on Tilia spp. in city street trees and nurseries throughout Wisconsin, probably because of increased use of these trees. Our objective was to gain a better understanding of the seasonal biology and potential management strategies for this important pest. We evaluated the effectiveness of three systemic insecticides, imidacloprid, thiamethoxam, and disulfoton, and a mechanical control method of chipping linden borer-infested wood as a means of reducing S. vestita larval survival, subsequent emergence, and oviposition. Autumn and spring soil injections of imidacloprid to linden borer infested Tilia cordata'Greenspire' nursery stock (< 11.4 cm in diameter at breast height [dbh]) provided >90% control. Autumn soil injections of imidacloprid and thiamethoxam and a spring granular soil application treatment of disulfoton applied to larger (>22 cm dbh) Tilia spp. did not effectively control linden borer at the application rates tested. Chipping infested Tilia spp. effectively destroyed linden borer larvae, pupae, and adults. Arborists and landscape managers should consider chipping felled Tilia spp. trees infested with S. vestita to prevent adults from potentially attacking nearby susceptible trees. PMID- 17849887 TI - Host plant susceptibility to the swede midge (Diptera: Cecidomyiidae). AB - The relative resistance and susceptibility of various cruciferous plants to swede midge, Contarinia nasturtii (Kieffer) (Diptera: Cecidomyiidae), damage was investigated to provide growers with planting recommendations and to identify potential sources of resistance to the swede midge. Broccoli cultivars experienced more severe damage than cabbage, cauliflower, and Brussels sprouts. The broccoli 'Paragon', 'Eureka', and 'Packman' are highly susceptible to the swede midge, whereas 'Triathlon' and 'Regal' showed reduced susceptibility to damage and slower development of damage symptoms. No differences were found between normal and red cultivars of cabbage and cauliflower in damage severity and progression of damage symptoms. Four new plant species (Brassica juncea Integlifolia group, Erucastrum gallicum (Willd.) O. E. Shulz., Lepidium campestre (L.) R.Br., and Capsella bursa-pastoris (L.) Medic.) are reported as hosts of the swede midge. The weed species Descurainia sophia (L.) Webb, Camelina microcarpa Andrz. ex Dc., and Erysimum cheiranthoides L. exhibited no damage symptoms, and they seem to be nonhost crucifers for the swede midge. PMID- 17849888 TI - Distribution, abundance, and seasonal ecology of Listronotus maculicollis (Coleoptera: Curculionidae) on golf courses in Quebec, Canada. AB - The weevil Listronotus maculicollis Dietz (Coleoptera: Curculionidae) is a major pest of annual bluegrass, Poa annua L., on golf courses in northeastern North America. To determine the distribution, abundance, and seasonal ecology of L. maculicollis on golf courses in Quebec, Canada, we sampled 19 golf courses (GC1 GC19) from different geographic and climatic conditions during 2001, 2002, and 2003. L. maculicollis was found on all golf courses except GC19, which was located in northeastern Quebec. In most sites, L. maculicollis completed two generations per year. A linear regression model comparing L. maculicollis larval densities as a function of spatial coordinates revealed that L. maculicollis were more abundant in western Quebec than in eastern Quebec. Pearson correlations on the probability of both L. maculicollis larval and pupal presence with soil parameters indicated significant positive correlations for fine sand (larvae) and soil pH (pupae) and negative correlations for gravel. PMID- 17849889 TI - Effect of diatomaceous earth and Trichoderma harzianum T-22 (Rifai strain KRL AG2) on the fungus gnat Bradysia sp. nr. coprophila (Diptera: Sciaridae). AB - This study, consisting of three experiments, was designed to assess whether diatomaceous earth, when applied to the surface of growing media, reduces adult fungus gnat Bradysia sp. nr. coprophila (Diptera: Sciaridae) emergence or inhibits the females from laying eggs; and whether fungus gnat adults are attracted to the fungus Trichoderma harzianum T-22 (Rifai strain KRL-AG2) under laboratory conditions. In the first two experiments, diatomaceous earth was applied at two different thicknesses (3.1 and 6.3 mm) and conditions (dry and moist) to the surface of a growing medium (Universal SB 300 Mix) after the growing medium had been artificially inoculated with second or third instars of fungus gnats, or before female fungus gnat adults were released into each deli squat container. In the third experiment, preparations of the fungus T. harzianum at the highest recommended label rate (0.889 kg/m3) were amended into the growing medium and processed 24, 48, or 72 h before use in a series of three two-choice trials with a two-armed experimental arena. In the first two experiments, the dry or moist layers of diatomaceous earth, in general, did not affect fungus gnats in terms of preventing adult emergence or egg laying by the females. During the course of these experiments, we observed that the diatomaceous earth dry treatments expanded as a result of absorbing moisture from the growing medium, creating fissures that allowed the fungus gnat larvae to pupate and females to lay eggs. In the third experiment, fungus gnat adults were not attracted to the T. harzianum treatments in any of the trials. PMID- 17849890 TI - Sprayable microencapsulated sex pheromone formulations for mating disruption of four tortricid species: effects of application height, rate, frequency, and sticker adjuvant. AB - Several application parameters of microencapsulated (MEC) sex pheromone formulations were manipulated to determine their impact on efficacy of disruption for codling moth, Cydia pomonella (L.); oriental fruit moth, Grapholita molesta (Busck); obliquebanded leafroller, Choristoneura rosaceana (Harris); and redbanded leafroller, Argyrotaenia velutinana (Walker). Depending on the experiment, the formulations evaluated were those formerly manufactured by 3M Canada (London, ON, Canada) or those that are currently available from Suterra LLC (Bend, OR). The efficacy of MEC formulations applied by air-blast sprayer evenly throughout the entire canopy of 2-3-m-tall apple (Malus spp.) trees was equivalent to treatments in which targeted applications of MECs were made to the lower or upper 1.5 m of the canopy (at equivalent overall rates) for oriental fruit moth and both leafroller species. The realized distribution of deposited microcapsules within the tree canopy corresponded well with the intended heights of application within the canopy. The additional coapplication of the pine resin sticker Nu-Film 17 increased efficacy but not longevity of MEC formulations for oriental fruit moth; this adjuvant had no added effects for codling moth or leafroller formulations. Increasing the rate of active ingredient (AI) per hectare by 20-30-fold (range 2.5-75.0 g/ha) did not improve the disruption efficacy of MECs for codling moth or either leafroller species when both low and high rates were applied at equivalent frequencies per season. A low-rate, high frequency (nine applications per season) application protocol was compared with a standard protocol in which two to three applications were made per season, once before each moth generation for each species. The low-rate, high-frequency protocol resulted in equivalent or better disruption efficacy for each moth species, despite using two-fold less total AI per hectare per season with the former treatment. The low-rate, frequent-application protocol should make the use of MEC formulations of synthetic pheromone more economical and perhaps more effective. PMID- 17849891 TI - Evaluation of treatment success and patterns of reinfestation of the Formosan subterranean termite (Isoptera: Rhinotermitidae). AB - Spread of the Formosan subterranean termite, Coptotermes fornwsanus Shiraki (Isoptera: Rhinotermitidae), is connected with the transport of infested wood, in particular, railroad ties. Therefore, efficient treatment of infestations, especially along railroads, is imperative to prevent further termite damage and spread. Evaluation of treatment success hinges on the ability to assign infestation sites to colonies and compare colony identity before and after treatment. Because colonies of the Formosan subterranean termite can be headed by a pair of reproductives (simple families) or by multiple reproductives (extended families), the question arises whether the breeding system of a colony influences treatment success and whether treatment of an area might have an impact on the breeding system. We used microsatellite genotyping to compare colony affiliation and breeding systems of Formosan termites infesting the Riverfront Railroad, New Orleans, LA, before and after treatment with 0.5% noviflumuron. Before treatment, four colonies were simple families, and 11 colonies were extended families. A year after treatment began, all treated colonies had vanished and did not reappear during this study. One colony from an untreated monitoring station moved into a nearby station after treatment. Colonies that were detected after treatment consisted of 12 simple families and six extended families; extended families found after treatment contained a higher number of reproductive neotenics than the extended families found before treatment. Extended families were more likely than simple families to move into inground stations that had been previously occupied by termite colonies. PMID- 17849892 TI - Foraging populations and distances of the desert subterranean termite, Heterotermes aureus (Isoptera: Rhinotermitidae), associated with structures in southern Arizona. AB - Mark-release-recapture studies were conducted on foraging populations of Heterotermes aureus (Snyder) (Isoptera: Rhinotermitidae) associated with three structures in Tucson, AZ. Foraging population estimates ranged from 64,913 to 307,284 termites by using the Lincoln Index and from 75,501 to 313,251 termites using the weighted mean model. The maximum distance between monitors ranged from 26 to 65 m, with minimum total foraging distance ranging between 297 and 2,427 m. Characterizations of the cuticular hydrocarbons of foraging groups were qualitatively identical. Quantitative similarities within sites and differences among sites suggested that each site was occupied by a single colony during the sampling period. The colony at each site had a proportion of soldiers (0.135, 0.069, and 0.040) that was significantly different from the colonies at each of the other sites. From this study, we question the assumption of equal mixing of marked H. aureus foragers throughout the occupied collars around structures. PMID- 17849893 TI - Field evaluation of potential control strategies against the invasive eastern subterranean termite (Isoptera: Rhinotermitidae) in Chile. AB - Four different termite control strategies consisting of two soil treatments with cypermethrin and fipronil and two bait treatments with hexaflumuron and sulfluramid were evaluated for their efficacy and potential for controlling the invasive eastern subterranean termite, Reticulitermes flavipes (Kollar) (Isoptera: Rhinotermitidae), in Quillota and Valparaiso, Chile. Monitoring stations were installed at all sites to measure the overall termite activity next to and at distances up to 30 m away from infested structures, most being 3-5 m. Foraging activity was extremely seasonal with the maximum consumption rates occurring from January to April. Termite foraging activity was low from July to September. After treatments in January 2003, there was a significant decrease in wood consumption, percentage of active stations, and numbers of termites in traps for the first 6 mo with hexaflumuron baits. No significant change in R. flavipes foraging activity was observed on wood consumption and percentage of active stations for sulfluramid bait or cypermethrin and fipronil soils treatments. The seasonal pattern of foraging activity remained unchanged for all treatments in 2004 and 2005, except structures baited with hexaflumuron. Feeding activity at the monitors in the area surrounding the hexaflumuron baits declined to 0 after January 2004. Alate flights occurred in approximately 38% of the structures treated with cypermethrin and sulfluramid bait in 2003 and in approximately 40% of the structures treated with cypermethrin, fipronil, and sulfluramid bait in 2004. Sulfluramid baits and cypermethrin soil treatments did not have any impact within a 15-m radius of the structures. Soils treatments of fipronil and cypermethrin prevented termites access in 75% of the homes. The number of active monitoring stations only declined within 2 m of the fipronil-treated zone. Hexaflumuron exhibited a reduction in activity for at least a 15-m radius. PMID- 17849894 TI - Distribution of Formosan subterranean termite (Isoptera: Rhinotermitidae) in Mississippi. AB - An extensive monitoring and survey program in Mississippi was conducted from 2000 to 2004 to investigate the distribution of the Formosan subterranean termite, Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae). Seventy-two towns from 22 counties in southern Mississippi were monitored with a total of 3914 traps that catch alates during the swarming season. In addition, 259 licensed pest management professionals in Mississippi were surveyed to determine the locations of termite infestations treated. The alates of C. formosanus were recovered in 12 counties with light traps, and termite infestations were documented in an additional 13 from data collected in the termite survey. Infestations of C. formosanus have been documented in urban, urban cluster, rural, and forested areas of Mississippi. However, the distribution in mean total capture of alates for 4 yr differed significantly among the four ecological areas with the highest percentage in forested areas (31%) and the lowest percentage in urban cluster areas (17%). Most of the infestations of C. formosanus were geographically distributed along the coastal areas of southern Mississippi from Gulfport to Pascagoula. The greatest total number of alates captured in light traps was documented in Pearl River County. Mass swarming of C. formosanus occurred primarily in May or June, depending on weather conditions. The number of documented counties with the evidence of large and widely dispersed swarms of C. formosanus in different ecological areas, and the increase in total annual alate captures from 2000 to 2003, suggest that this invasive termite species is now firmly established in Mississippi. PMID- 17849895 TI - Comparisons of malathion susceptibility, target sensitivity, and detoxification enzyme activity in nine field populations of Oxya chinensis (Orthoptera: Acrididae). AB - The malathion susceptibility, acetylcholinesterase (AChE) sensitivity, and the activity of selected detoxification enzymes including general esterase (EST) and glutathione S-transferase (GST) were compared among field populations of the grasshopper Oxya chinensis (Thunberg) (Orthoptera: Acrididae) collected from nine regions of China. Bioassay results showed that these populations had various levels of the susceptibility to malathion with the LDo values ranging from 1.4- to 22.6-fold compared with the most susceptible population (Xiangyuan or XY). The Jinnan (JN) population seemed to be malathion resistant (22.6-fold), whereas other populations exhibited 1.4- to 6.8-fold reduced malathion susceptibility with a rank order of Changan > Baodi > Hanzhong > Xinxiang > Yinchuan > Beidagang > Jinyuan. It seemed that the observed malathion resistance in the JN population was attributed to at least two resistance mechanisms, including increased EST activity (2.2-fold) and reduced sensitivity of AChE to inhibition by malaoxon (4.6-fold) compared with those of the XY population. In contrast, differential malathion susceptibilities in other populations may be due to increased activities of certain detoxification enzymes (e.g., EST and GST), reduced sensitivity of AChE, or other factors, which were not consistent across the populations examined. Such differential susceptibilities to malathion were likely due to different population habitats (e.g., grasslands, rice [Oryza sativa L.] producing regions) with very different insecticide application histories and pest management practices. PMID- 17849896 TI - Bean alpha-amylase inhibitors in transgenic peas inhibit development of pea weevil larvae. AB - This glasshouse study used an improved larval measurement procedure to evaluate the impact of transgenic pea, Pisum sativum L., seeds expressing a-amylase inhibitor (AI)-1 or -2 proteins on pea weevil, Bruchus pisorum L. Seeds of transgenic 'Laura' and 'Greenfeast' peas expressing alpha-(AI)-1 reduced pea weevil survival by 93-98%. Larval mortality occurred at an early instar. Conversely, in nontransgenic cultivars, approximately 98-99% of the pea weevils emerged as adults. By measuring the head capsule size, we determined that larvae died at the first to early third instar in alpha-(AI)-1 transgenic peas, indicating that this inhibitor is highly effective in controlling this insect. By contrast, transgenic Laura and 'Dundale' expressing alpha-(AI)-2 did not affect pea weevil survival, but they did delay larval development. After 77 d of development, the head capsule size indicated that the larvae were still at the third instar stage in transgenic alpha-(AI)-2 peas, whereas adult bruchids had developed in the nontransgenic peas. PMID- 17849897 TI - Baseline responses of Alphitobius diaperinus (Coleoptera: Tenebrionidae) to spinosad, and susceptibility of broiler populations in Eastern and Southern Australia. AB - Spinosad was proposed as a potential chemical for control of lesser mealworm, Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae), in Australian broiler houses after the detection of strong cyfluthrin resistance in many beetle populations. In 2004-2006, spinosad susceptibility of 13 beetle populations from eastern and southern Australian broiler houses and a cyfluthrin/fenitrothion resistant reference population was determined using topical application, and was compared with the susceptibility of an insecticide-susceptible reference population. Comparisons of dose-response curves and baseline data showed that all populations, including the insecticide-susceptible population, were roughly equivalent in their response to spinosad, indicating no preexisting spinosad resistance. Two field populations, including the resistant reference population, which had confirmed cyfluthrin/fenitrothion-resistance, showed no cross resistance to spinosad. There was no significant correlation between beetle weight and LC9.9. A discriminating concentration of 3% spinosad was set to separate resistant and susceptible individuals. Considering the levels of spinosad resistance that have been recorded in other insect pests, the sustained future usefulness of spinosad as a broiler house treatment will rely on effective integrated beetle management programs combined with carefully planned chemical use strategies. PMID- 17849898 TI - Effects of proportion and configuration of Bacillus thuringiensis cotton on pest abundance, damage, and yield. AB - Bacillus thuringiensis (Bt) transgenic cotton, Gossypium hirsutum L., kills several economically important pests, reducing injury and increasing yields. Refuges of non-Bt cotton are currently planted with Bt cotton in different designs to slow pest resistance evolution. To compare the effects of differences in Bt/non-Bt plant heterogeneity found in different refuge designs on square (flower bud) damage, abscissions, sap-feeding herbivore densities, and yield in cotton, four types of 24-row cotton plots were planted in 2001 and 2002: 1) seed mixtures of Bt and non-Bt varieties, 2) 12-row strips of Bt and non-Bt, 3) solid Bt, and 4) solid non-Bt. For both years cotton bollworm, Helicoverpa zea (Boddie), damage was less in solid Bt plots than strips and mixtures and all were less than solid non-Bt plots. Cotton fleahopper, Pseudatomoscelis seriatus (Reuter), damage was affected by refuge, but only in 2002 when damage was greater in solid Bt plots than all other plots and greater in strips than solid non-Bt plots. Abscissions were least in solid non-Bt plots, and less in mixtures and strips than solid Bt plots. In 2001, western flower thrips, Frankliniella occidentalis (Pergande), density was greatest in mixtures, whereas sweetpotato whitefly, Bemisia tabaci (Gennadius), was greatest in solid Bt plots, and greater in mixtures than solid non-Bt plots. Yield also was affected by refuge, it was greater for solid Bt plots than for solid non-Bt plots and mixtures in 2001, but the reverse was true in 2002. PMID- 17849899 TI - Effects of pyriproxyfen on California red scale (Hemiptera: Diaspididae) development and reproduction. AB - Two life stages of a laboratory colony of California red scale, Aonidiella aurantii (Maskell) (Hemiptera: Diaspididae), were exposed to 10 concentrations of pyriproxyfen to evaluate the effect of this insect growth regulator (IGR) on scale development and fecundity. First instars exposed to pyriproxyfen responded with mortality during the first and second molts. Second instars were more tolerant of pyriproxyfen than were first instars, indicating that growers should treat California red scale in the field before the first molt to achieve maximum efficacy. Male scales responded with an LC50 12-fold lower and an LC90 47-fold lower than was observed for female scales. Female scales that survived first instar exposure to pyriproxyfen experienced reduced fecundity with increasing pyriproxyfen concentration. Reduced fecundity was due to reduced survival of the females rather than sterility. Results from this study provide baseline California red scale susceptibility data for pyriproxyfen, and they suggest that 1 ppm pyriproxyfen can be used as a concentration that would discriminate between susceptible and resistant populations of scales. Field monitoring for incipient pyriproxyfen resistance in California red scale should be implemented in the San Joaquin Valley of California, and if resistance is detected, integrated resistance management strategies should be used to slow the progression of resistance. PMID- 17849900 TI - A novel molecular approach to assess mating success of sterile Ceratitis capitata (Diptera: Tephritidae) males in sterile insect technique programs. AB - Areawide sterile insect technique (SIT) programs against Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), are increasingly implemented worldwide. A key issue in SIT is to assess mating success of released sterile males, which could be currently estimated by egg hatchability and by stored sperm head measurements. We report here on a novel molecular approach that would allow detecting the presence of Mediterranean fruit fly sterile male sperm in the female spermathecae under field conditions, as a precise marker to assess mating performance. The simplicity (only two polymerase chain reactions) and reliability of this method, jointly with the capability to detect Vienna sperm in wild Mediterranean fruit fly maintained in monitoring traps for 7 d under field conditions, suggest that it could be an efficient tool when coupled with areawide SIT programs. PMID- 17849901 TI - Quantitative trait loci mapping of resistance to Laodelphax striatellus (Homoptera: Delphacidae) in rice using recombinant inbred lines. AB - Laodelphax striatellus Fallen (Homoptera: Delphacidae), is a serious pest in rice, Oryza sativa L., production. A mapping population consisting of 81 recombinant inbred lines (RILs), derived from a cross between japonica' Kinmaze' and indica' DV85' rice, was used to detect quantitative trait loci (QTLs) for the resistance to L. striatellus. Seedbox screening test (SST), antixenosis test, and antibiosis test were used to evaluate the resistance response of the two parents and 81 RILs to L. striatellus at the seedling stage, and composite interval mapping was used for QTL analysis. When the resistance was measured by SST method, two QTLs conferring resistance to L. striatellus were mapped on chromosome 11, namely, Qsbph11a and Qsbph11b, with log of odds scores 2.51 and 4.38, respectively. The two QTLs explained 16.62 and 27.78% of the phenotypic variance in this population, respectively. In total, three QTLs controlling antixenosis against L. striatellus were detected on chromosomes 3, 4, and 11, respectively, accounting for 37.5% of the total phenotypic variance. Two QTLs expressing antibiosis to L. striatellus were mapped on chromosomes 3 and 11, respectively, explaining 25.9% of the total phenotypic variance. The identified QTL located between markers XNpb202 and C1172 on chromosome 11 was detected repeatedly by three different screening methods; therefore, it may be important to confer the resistance to L. striatellus. Once confirmed in other mapping populations, these QTLs should be useful in breeding for resistance to L. striatellus by marker-assisted selection of different resistance genes in rice varieties. PMID- 17849902 TI - Assessing stink bug resistance in soybean breeding lines containing genes from germplasm IAC-100. AB - Sixty-five soybean, Glycine max (L.) Merr., breeding lines containing the stink bug resistant 'IAC-100' in their pedigrees were evaluated for their resistance to stink bug, primarily southern green stink bug, Nezara viridula L., feeding in replicated field trials from 2001 to 2005. Plots were sampled throughout the season for stink bug abundance, and, at harvest, seed samples were rated for stink bug-induced kernel damage. Individual seeds were categorized as having none, light, moderate, or heavy damage plus 100-seed wt and plot yields were determined. Both ground cloth and sweep net sampling procedures were used to compare stink bug densities between the soybean entries. Stink bug densities varied between years; however, in the years when populations exceeded four per row-meter or six per 25 sweeps, there were more damaged soybean seeds (>25%) in the entries with higher stink bug numbers. During the first 2 yr of evaluations, the mean stink bug-damaged soybean seeds ranged from 10.0 to 38.2%. From these differential responses, 28 entries were selected for continued study in 2003 2004. In 2003, stink bug-damaged soybean seeds were low, with damage ranging from 2.9 to 18.2%. In 2004, stink bug damage ranged from 8.8 to 53.2%. From these 28 lines, 12 entries were selected for an advanced field screening trial in 2005, including the IAC-100 and 'Hutcheson'. Damaged soybean seeds ranged from 18.5 to 54.1% among these 12 entries in 2005, under heavy stink bug pressure. From these evaluations, four breeding lines with either Hutcheson X IAC-100 or IAC-100 x 'V71-370' in their genealogy were identified as possible breeding material for future soybean stink bug resistance cultivar development. PMID- 17849903 TI - Resistance to Aphis glycines (Hemiptera: Aphididae) in various soybean lines under controlled laboratory conditions. AB - The soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), a pest of soybean, Glycine max (L.) Merr., native to Asia, has recently become a principal pest of this crop in many areas of North America. Insecticides are currently used to manage A. glycines, but host plant resistance is a potential alternative management tool. Tests were conducted to determine resistance to A. glycines among soybean lines. 'Cobb,' 'Tie-feng 8,' and 'Jackson' were resistant to population growth of A. glycines compared with 'Cook' and '91B91,' a susceptible control. Antibiosis was evident in Cobb, Jackson, and Tie-feng 8 from lowered survival of first generation A. glycines, and in Cobb, Jackson, Tie-feng 8, and 'Braxton' from diminished reproduction by first generation aphids. Antixenosis was apparent in Cobb and Jackson during initial infestation of aphid population growth tests, because A. glycines were unsettled and dispersed readily from placement points on unifoliolate leaves. Decreased nymphiposition by A. glycines occurred on Cobb and Jackson, and it may have been caused by antibiotic chemicals in these lines, failure of aphids to settle, or both. Differences in distribution of A. glycines between unifoliolate leaves and other shoot structures suggest that unifoliolate leaves were acceptable feeding sites on 91B91 and Cook, whereas unifoliolate leaves and other shoot structures were roughly equally acceptable feeding sites on Braxton, Tie-feng 8, Jackson, and Cobb. However, Jackson and Cobb had relatively low counts of A. glycines on shoots that may have been due to abandonment of plants by aphids, decreased aphid survival, or both. Results confirm earlier findings that Jackson is a strong source of resistance to A. glycines, and they suggest that Tie-feng 8, Braxton, and especially Cobb are potentially useful sources of resistance. PMID- 17849904 TI - Genetic basis of resistance to fall armyworm (Lepidoptera: Noctuidae) and southwestern corn borer (Lepidoptera: Crambidae) leaf-feeding damage in maize. AB - Leaf-feeding damage by first generation larvae of fall armyworm, Spodopter frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), and southwestern corn borer, Diatraea grandiosella Dyar (Lepidoptera: Crambidae), cause major economic losses each year in maize, Zea mays L. A previous study identified quantitative trait loci (QTL) contributing to reduced leaf-feeding damage by these insects in the maize line Mp704. This study was initiated to identify QTL and their interactions associated with first generation leaf-feeding damage by fall armyworm and southwestern corn borer. QTL associated with fall armyworm and southwestern corn borer resistance in resistant line Mp708 were identified and compared with Mp704. Multiple trait analysis (MTA) of both data sets was then used to identify the most important genetic regions affecting resistance to fall armyworm and southwestern corn borer leaf-feeding damage. Genetic models containing four and seven QTL explained southwestern corn borer and fall armyworm resistance, respectively, in Mp708. Key genomic regions on chromosomes 1, 5, 7, and 9 were identified by MTA in Mp704 and Mp708 that confer resistance to both fall armyworm and southwestern corn borer. QTL regions on chromosomes 1, 5, 7, and 9 contained resistance to both insects and were present in both resistant lines. These regions correspond with previously identified QTL related to resistance to other lepidopteran insects, suggesting that broad-spectrum resistance to leaf feeding is primarily controlled by only a few genetic regions in this germplasm. PMID- 17849905 TI - Influence of wolbachia infection on the fitness of the stored-product pest Liposcelis tricolor (Psocoptera: Liposcelididae). AB - Wolbachia are maternally inherited intracellular bacteria (Rickettsiaceae) that infect a wide range of arthropods and nematodes and that are associated with various reproductive abnormalities in their hosts. In this study, the effects of removal of Wolbachia infection on development, survival, and reproduction of Liposcelis tricolor Badonnel (Psocoptera: Liposcelididae) were investigated in laboratory. The Wolbachia-free strain was obtained by the removal of Wolbachia infection by using 1% rifampicin treatment on the Wolbachia-infected strain (control) for 4 wk, and no Wolbachia gene product was detected in this strain throughout the experiment. The results showed that the removal of Wolbachia infection had negative effects on the fitness of L. tricolor. Compared with the control strain, the Wolbachia-free strain (both in the first [F1] and second [F2] generation) had prolonged developmental times, reduced survivorship of immature stages, and reduced fecundity and longevity, resulting in much smaller rm values. Using rm values, the fitness for Wolbachia-free F1 and F2 relative to the control were calculated as 0.45 and 0.27, respectively. The results of this study further confirmed our previous conclusion that Wolbachia infection have positive effects on fecundity and fertility of L. tricolor, and for optimal reproduction of L. tricolor, Wolbachia must be present in psocids. PMID- 17849906 TI - Survival of indianmeal moth and navel orangeworm (Lepidoptera: Pyralidae) at low temperatures. AB - Concerns over insect resistance, regulatory action, and the needs of organic processors have generated renewed interest in developing nonchemical alternative postharvest treatments to fumigants used on dried fruits and nuts. Low temperature storage has been identified as one alternative for the Indianmeal moth, Plodia interpunctella (Hiibner), and navel orangeworm, Amyelois transitella (Walker) (Lepidoptera: Pyralidae), common postharvest pests in California dried fruits and nuts. The response of eggs, nondiapausing larvae, and pupae of both species to exposure to low temperatures (0, 5, and 10 degrees C) was evaluated. Eggs of both species were the least tolerant of low temperatures. At 0 and 5 degrees C, pupae were most tolerant, but at 10 degrees C, nondiapausing larvae of both species were most tolerant, with lethal time (LT)95 values of 127 and 100 d for Indianmeal moth and navel orangeworm, respectively. The response of diapausing Indianmeal moth larvae to subfreezing temperatures also was evaluated. Diapausing larvae were very cold tolerant at -10 degrees C, with LT95 values of 20 and 17 d for long-term laboratory and recently isolated cultures, respectively. Diapausing larvae were far less tolerant at lower temperatures. At 15 degrees C, LT95 values for both cultures were <23 h, and at -20 degrees C, LT95 values were <7 h. Refrigeration temperatures of 0-5 degrees C should be useful in disinfesting product contaminated with nondiapausing insects, with storage times of 3 wk needed for adequate control. Relatively brief storage in commercial freezers, provided that the temperature throughout the product was below -15 degrees C for at least 48 h, also shows potential as a disinfestation treatment, and it is necessary when diapausing Indianmeal moth larvae are present. PMID- 17849907 TI - House fly (Diptera: Muscidae) activity near baits containing (Z)-9-tricosene and efficacy of commercial toxic fly baits on a southern California dairy. AB - Sticky card captures of house flies, Musca domestica L. (Diptera: Muscidae), were used to compare efficacy of screen-covered baits containing sugar, sugar and 0.1% (Z)-9-tricosene, sugar and 1.0% (Z)-9-tricosene, Golden Malrin [1.1% methomyl and 0.049% (Z)-9-tricosene], and Quick-Bayt [0.5% imidacloprid and 0.1% (Z)-9 tricosene]. The QuickBayt treatment caught more flies per hour (mean = 116.5) than sugar alone (mean = 81.0), but the addition of (Z)-9-tricosene to sugar did not increase fly capture compared with sugar alone. More males (65% of total) than females were collected on the sticky cards for all treatments. Fly kill by plain sugar (control) and the commercial baits Golden Malrin, QuikStrike Fly Abatement strips (1.0% nithiazine), and QuickBayt was tested over a 90-min period. An average of 1.4, 5.6, 363.0, and 1,266.0 flies were killed using sugar, Golden Malrin, QuikStrike, and QuickBayt, respectively. The similarity between Golden Malrin and plain sugar reflects severe resistance to this once effective methomyl bait. A no-choice feeding assay using lab-reared methomyl-susceptible and methomyl-resistant house flies was conducted with and without (Z)-9 tricosene. Adult mortality was significantly higher in the methomyl-susceptible strain exposed to treatments containing methomyl. Lower consumption of the methomyl treatments by resistant flies suggested resistance was behavioral and mortality was not influenced by (Z)-9-tricosene for either fly strain. PMID- 17849908 TI - [Post-mortem diagnosis of leptospirosis in two dogs]. AB - Leptospirosis was diagnosed post-mortem in a 2-year-old male Dogo Argentino and a 7-week-old male Foxhound puppy. The two cases were unrelated. Clinical symptoms were mainly confined to the gastro-intestinal tract. Pathological lesions were suggestive of acute leptospirosis. Leptospires infection was confirmed by serological (indirect IgM/Ig6 ELISA and MAT) and immunohistochemical techniques. PMID- 17849909 TI - [Diagnostic aspects of Borrelia-infections in dogs]. AB - This paper discusses the problem of diagnosing borreliosis (Lyme disease) in dogs. A prospective cohort study in the Kempen district, a known Borrelia focus in The Netherlands, showed that dogs with the presumptive symptoms of borreliosis, episodic malaise and lameness, had significantly higher and longer lasting anti-Borrelia IgG titers than asymptomatic dogs. A small part of these dogs also had antibodies directed against the IR6 (C6) antigen which indicates persistent active Borrelia infection. A few typical case histories are presented. Dogs with episodic malaise and lameness with persistent high IgG titers are suspect of suffering from borreliosis. IR6 antibodies make this diagnosis likely. Initially, such patients should be treated with doxycyclin (10 mg/kg 1dd) for 10 days. If the symptoms recurr within a few months, a longer treatment (eg 6 weeks) should be considered. Bernese mountain dogs were strongly over-represented among the borreliosis patients in the cohort study and most high titered samples among those submitted for--diagnostic--serology appear to come from this breed, which suggests that these dogs have difficulties with clearing this tick-borne infection. PMID- 17849910 TI - [Efficacy of an emergency vaccine against foot and mouth disease in pigs]. PMID- 17849911 TI - [Euthanasia without beauty contest price]. PMID- 17849912 TI - [Research on demand. Veterinarian in the business world]. PMID- 17849913 TI - ["A large society has a louder voice". New chairman for the interest of veterinarians on the pay role]. PMID- 17849914 TI - [Internet commerce versus expensive veterinary clinic]. PMID- 17849915 TI - [Again, mismanagement]. PMID- 17849916 TI - [Medicine and veterinary medicine. Extraordinarily many comparisons but still different]. PMID- 17849917 TI - [Metacam and joint pathology in cats]. PMID- 17849918 TI - Clear communication--accept nothing less. PMID- 17849919 TI - Evidence base for developing a palliative care service. AB - A retrospective study was designed to collect objective data to support need for a palliative care service at Mayo Clinic Hospital. Based on the results, a pilot program was initiated. PMID- 17849920 TI - Postoperative continuous peripheral nerve blockade in the lower extremity total joint arthroplasty population. AB - In certain patient populations, postoperative pain management increasingly relies on more localized anesthetic methods rather than systemic medications. Use of methods such as continuous peripheral nerve blockade demonstrates improved patient satisfaction and decreased length of hospital stay. This technique of pain management and its associated use in patients following total joint arthroplasty are examined. PMID- 17849921 TI - Development of an evidence-based protocol for reduction of indwelling urinary catheter usage. AB - Studies indicate 40% of indwelling urinary catheters are unnecessary in hospitalized patients (Gardam, Amihod, Orenstein, Consolacion, & Miller, 1998; Gokula, Hickner, & Smith, 2004). The results of a protocol developed to limit catheter use are described. PMID- 17849922 TI - Advance directives: curriculum content and preparation of nursing students. AB - The amount of didactic content on advance directives in nursing curricula is addressed. Conclusions have relevance to the limited knowledge of practicing nurses on the subject of advance directives. PMID- 17849923 TI - A clinical advancement process revisited: a descriptive study. AB - Clinical advancement programs are not evaluated often for effectiveness and participant satisfaction. The advancement committee at this community hospital made the commitment to evaluate participant satisfaction periodically. Revisions were made in the program based on the evaluation findings and implemented in 2002. This re-evaluation was conducted to determine participant satisfaction. PMID- 17849924 TI - Medication errors in a rural hospital. AB - The purpose of this investigation was to compare and contrast three nursing shifts in a small rural Midwestern hospital with regard to the number of reported medication errors, the units on which they occurred, and the types and severity of errors. Results can be beneficial in planning and implementing a quality improvement program in the area of medication administration with the nursing staff. PMID- 17849925 TI - Positive steps towards negative pressure wound therapy. PMID- 17849926 TI - An overview of stem cell transplant as a treatment for cancer. PMID- 17849927 TI - Critique of 'advance directives: curriculum content and preparation of nursing students'. AB - This research study reflects an important topic for the practice of nursing and nursing education. The descriptive design utilized clear sampling methods. Clear research questions were identified; however, other data analysis methods may have been more appropriate. Recommendations to increase advance directive content in educational programs should be preceded by an investigation of knowledge retention and other factors impacting staff nurses' comfort in working with advance directives in the clinical setting. PMID- 17849928 TI - Are you 'nuts'? Lessons from Southwest Airlines. PMID- 17849929 TI - The art of truth telling: handling failure with disclosure and apology. AB - How the leader handles failures determines how people perceive the true character of the leader. The power of transparency and apology is an option that leaders haven't universally embraced as rapidly as clinicians. However, there is a plethora of information that tells us there is almost magic in the power of the process of truth telling and apology. There are sentinel events and near misses associated with leadership and management, as well as the clinical process of health care. PMID- 17849930 TI - Hypnotic sedative drugs. PMID- 17849931 TI - A template for safe and concise handovers. PMID- 17849932 TI - Assessing pain in persons with dementia. PMID- 17849933 TI - Asthma. PMID- 17849934 TI - Validation of the Adolescent Concerns Measure (ACM): evidence from exploratory and confirmatory factor analysis. AB - This article reports the development and initial validation of scores obtained from the Adolescent Concerns Measure (ACM), a scale which assesses concerns of Asian adolescent students. In Study 1, findings from exploratory factor analysis using 619 adolescents suggested a 24-item scale with four correlated factors- Family Concerns (9 items), Peer Concerns (5 items), Personal Concerns (6 items), and School Concerns (4 items). Initial estimates of convergent validity for ACM scores were also reported. The four-factor structure of ACM scores derived from Study 1 was confirmed via confirmatory factor analysis in Study 2 using a two fold cross-validation procedure with a separate sample of 811 adolescents. Support was found for both the multidimensional and hierarchical models of adolescent concerns using the ACM. Internal consistency and test-retest reliability estimates were adequate for research purposes. ACM scores show promise as a reliable and potentially valid measure of Asian adolescents' concerns. PMID- 17849935 TI - Peer group membership and a sense of belonging: their relationship to adolescent behavior problems. AB - This study explored three aspects of peer group membership in adolescence: peer group affiliation, the importance of group membership, and a sense of peer group belonging. Each is considered in relationship to adolescents' behavior problems as measured by the Achenbach Youth Self-Report. Participants included an ethnically and socioeconomically diverse sample of 733 adolescents ranging in age from 11 to 18 years. Girls reported more internalizing problems and boys reported more externalizing problems. Girls also reported a higher sense of peer group belonging than boys. When controlling for adolescent age, gender, ethnicity, parent's educational level, and family structure, a sense of peer group belonging was negatively related to internalizing and externalizing behavior problems. Adolescents who viewed peer group membership as very important to them and had a positive sense of peer group belonging had significantly fewer behavior problems than those who viewed peer group membership as very important but did not have a positive sense of peer group belonging. PMID- 17849936 TI - Social isolation, psychological health, and protective factors in adolescence. AB - This study investigates the relationships among social isolation, psychological health, and protective factors in adolescents. Feelings of social isolation may influence psychological health in adolescents, but protective factors such as family connectedness, school connectedness, and academic achievement may also play a key role. The sample included 4,746 adolescents from 31 middle and high schools. Participants responded to 221 survey questions regarding peer relationships, psychological health, school connectedness, family relationships, and academic achievement. The findings revealed that social isolation was associated with an increased risk for depressive symptoms, suicide attempts, and low self-esteem. Protective factors influenced associations between social isolation and psychological health. Implications for prevention such as building healthy peer relationships, promoting family connectedness, and developing school based interventions are discussed. PMID- 17849937 TI - Unique pathways to resilience across cultures. AB - An international mixed methods study of resilience of 14 sites in eleven countries identified seven tensions that youth resolve in culturally specific ways. Resolution of these tensions is foundational to experiences of resilience. This paper reports on the qualitative findings from interviews with 89 youth. Results support a culturally embedded understanding of positive youth development that better accounts for young people's resilience in western and non-western countries. Specifically, the seven tensions identified include: access to material resources, relationships, identity, cohesion, power and control, social justice, and cultural adherence. Findings show that no one pattern in the resolution of these tensions predicts resilience better than another. A case study of a Palestinian boy demonstrates the intersection of the seven tensions and the uniqueness of their resolution. The implications of this work for interventions is discussed. PMID- 17849938 TI - Psychosocial factors associated with reports of physical dating violence among U.S. adolescent females. AB - The present study, based upon the national 2005 Youth Risk Behavior Survey of U.S. high school students, provides the most current and representative data on dating violence among adolescent females (N = 7,179). The dependent variable was physical dating violence. The independent variables included four dimensions: violence, suicide, substance use, and sexual risk behavior. Unadjusted odds ratios (OR) and 95% confidence intervals (CI), were examined followed by multivariate logistic regression analyses, which included all significant independent variables from the bivariate analyses. Adjusted OR and 95% CI were computed to assess the significance of the relationships. In terms of prevalence, 10.3% of female adolescents reported experiencing physical dating violence. Black girls (OR = 1.47) and girls who reported sad/hopeless feelings (OR = 1.42) considered suicide (OR = 1.55), engaged in physical fighting (OR = 2.17), had recent sexual partners (OR = 2.10), or had unprotected sexual intercourse (OR = 1.70) were more likely to report physical dating violence. These findings suggest dating violence against adolescent females is widespread and associated with a host of other risk factors that deserve further attention through longitudinal research and intervention efforts. PMID- 17849939 TI - Differences in intelligence between nondelinquent and dropout delinquent adolescents. AB - This study examined differences in intelligence between dropout delinquent adolescents and nondelinquent adolescents in Israel. It was part of research aimed at using psychological tests to characterize dropout delinquents. The participants, 215 adolescents at a psychoeducational center, were divided into three groups and were tested using the WISC-R: dropout delinquent adolescents living in residential institutions, dropout delinquent adolescents living at home, and nondelinquent adolescents living at home and enrolled in the formal education system. Results showed significant differences among the three groups in Verbal IQ, Performance IQ, Total IQ, and the Freedom from Distractibility factor, and pointed out the relative weakness of the dropout delinquent groups. PMID- 17849940 TI - Feeling the beat: the meaning of rap music for ethnically diverse Midwestern college students--a phenomenological study. AB - Despite its national and international appeal, rap is considered one of the most controversial of music genres. Given the political charge it generates, rap music has spawned research across the social and health sciences. The majority of the research has investigated its impact on African Americans. Further, the research has tended to focus on negative aspects of the music; there has been a dearth of in-depth qualitative studies that explore how rap impacts the listener. Our phenomenological study explores that impact on ethnically diverse college students. Results indicate a profound psychological and educational effect and the discussion goes on to highlight the potential and innovative ways rap music can be utilized with adolescents in fields such as education, risk reduction programs, and counseling psychology. PMID- 17849941 TI - Effects of appearance-related testing on ethnically diverse adolescent girls. AB - The primary research question in this study was whether adolescents' experiences of and responses to teasing were related to the content of a tease and to particular ethnicity. Caucasian (n = 27) and African American adolescents (n = 22) between 12 to 17 years of age were asked to write about an experience of being teased regarding an aspect of appearance. Content analysis was used to examine responses. Participants' narrative revealed teasing about multiple aspects of their appearance including clothing, facial characteristics, weight, height, hair, and other physical characteristics. All participants voiced negative opinions about being teased. However, African Americans noted that some experiences with teasing were positive. Participants reported that they attempted to modify their appearance after being teased, especially about clothing. PMID- 17849942 TI - Cognitive and social influences on gang involvement among delinquents in three Chinese cities. AB - Inasmuch as research has held the increase in youth gang activities responsi ble for the escalating level of crime and delinquency in Chinese societies, ascertaining risk or protective factors of gang involvement among Chinese youths is crucial. The factors include those associated with social control, social learning, and cognitive development. To investigate these factors across different sociocultural contexts, we surveyed delinquents in three diverse Chinese cities-Hong Kong, Guangzhou, and Shanghai. Because of the sociocultural differences among the three cities, social control by parents and cognitive development are likely to be greater protective factors in terms of youths' gang involvement in Hong Kong, while social control by teachers is likely to be a greater protective factor in mainland cities. Results bear out these hypotheses. PMID- 17849943 TI - An investigation of Taiwanese early adolescents' self-evaluations concerning the Big 6 information problem-solving approach. AB - The study developed a Big 6 Information Problem-Solving Scale (B61PS), including the subscales of task definition and information-seeking strategies, information access and synthesis, and evaluation. More than 1,500 fifth and sixth graders in Taiwan responded. The study revealed that the scale showed adequate reliability in assessing the adolescents' perceptions about the Big 6 information problem solving approach. In addition, the adolescents had quite different responses toward different subscales of the approach. Moreover, females tended to have higher quality information-searching skills than their male counterparts. The adolescents of different grades also displayed varying views toward the approach. Other results are also provided. PMID- 17849944 TI - How instant messaging affects the satisfaction of virtual interpersonal behavior of Taiwan junior high school students. AB - Although Instant Messaging (IM) has established itself as one of the most popular modes of communication, little empirical research has explored how adolescents are affected by its use to satisfy their virtual interpersonal relationships. This research investigates cause and effect in the satisfaction of these relationships among adolescents in both their real and virtual life by using IM. Data were collected from 401 junior high school students via a questionnaire. Descriptive statistics, factor analysis, and SEM analysis methods were used to analyze the data. Primary findings indicate that (1) there is significant cause and effect on the adolescents' satisfaction with their interpersonal relationships between their real life and the virtual world (via IM); and (2) adolescents may enhance their interpersonal behavior by using IM, leading to an increase in satisfaction with their interpersonal relationships in the virtual world. PMID- 17849945 TI - Endothelial dysfunction in type 2 diabetes: effect of antioxidants. AB - Individuals with insulin resistance and diabetes mellitus have increased cardiovascular morbidity and mortality, caused in part by vascular complications. Endothelial dysfunction has been implicated in the pathogenesis of vascular diabetic disease. This abnormal function of the vasculature precedes cardiovascular disease and is associated with impaired endothelium-dependent vasorelaxation. The main etiology of the increased mortality and morbidity of type 2 diabetic patients is atherosclerosis. Increased production of free radicals is associated with the pathophysiology of diabetes, resulting in oxidative damage to lipids and proteins. Reduction of oxidative stress in diabetic patients may delay the onset of atherogenesis and the appearance of micro- and macrovascular complications. Alpha-lipoic acid (LA) is a multifunctional antioxidant that has been shown to have beneficial effects on polyneuropathy and on markers of oxidative stress in various tissues. This study was conducted to investigate the effects of LA on endothelial function in diabetic and hyperlipidemic animal models. Carbohydrate and lipid metabolism, endothelial function, plasma malondialdehyde (MDA) and urinary 8 hydroxydeoxyguanosine (8-OHdG) were assessed in non-diabetic controls (Wistar rats), untreated diabetic Goto-Kakizaki (GK) rats and, atherogenic diet (AD)-fed GK rats (fed with atherogenic diet only, treated with alpha-lipoic acid and treated with vehicle, for 3 months). AD resulted in a 3-fold increase in both total and non-HDL serum cholesterol levels and in a 2-fold increase triglyceride levels while endothelial function was significantly reduce MDA and 8-OHdG levels were higher in the GK and GK hyperlipidemic groups and were completely reversed by the antioxidant. Hyperlipidemic GK diabetic rats showed significantly reduced endothelial function that was partially improved with LA. Furthermore, lipoic acid significantly reduced serum cholesterol levels, without lowering HDL cholesterol. Alpha-lipoic acid supplementation represents an achievable adjunct therapy to improve endothelial function and reduce oxidative stress, factors that are implicated in the pathogenesis of atherosclerosis in diabetes. PMID- 17849946 TI - Pseudonormalization of transmitral pulsed doppler flow: A/e' ratio during the valsalva maneuver--a new discriminative index. AB - The Valsalva maneuver (VM) has frequently been suggested as a useful method in evaluation of left ventricular (LV) grade II diastolic dysfunction (DDII) through inversion of a pseudonormalized ratio between diastolic transmitral early (E) and late atrial (A) waves assessed by pulsed Doppler. The purpose of our study was to determine the sensitivity and specificity of E/A inversion during VM in LV DDII patients and its correlation with mitral annulus motion evaluated by tissue Doppler imaging (TDI). Using the echocardiographic criteria of the European Society of Cardiology for the diagnosis of diastolic dysfunction, we studied a group of 44 patients, 27 male, aged 59 +/- 14 years, with DDII (DDII-group) and compared them with a control group (N group) composed of 33 healthy individuals, 17 male, aged 36 +/- 9 years. Using transmitral pulsed Doppler analysis, we quantified the peak diastolic velocities of transmitral flow (E and A waves in cm/sec), pulmonary venous systodiastolic flow (PVF: S35 cm/sec) and the first aliasing LV diastolic flow propagation velocity by color M mode Doppler (PVF <45 cm/sec for LV DDII). Using TDI we measured the peak systolic (s'), and diastolic rapid filling (e') and atrial (a') velocities (Vm in cm/sec) at four points of the mitral annulus: adjacent to the interventricular septum (P4), and the lateral (P2), inferior (P3) and anterior (P4) LV walls. VM was performed by all patients, with repeated measurements of the above parameters (except for PVF) at the point of their maximum shift. RESULTS: Four patients in the DDII-group were excluded due to degradation of the acoustic window during VM. The sensitivity and specificity of E/A inversion during VM in diagnosing LV DDII were respectively 88% and 57%. On ROC curve analysis, the most discriminative index for DDII diagnosis A/e' > 4.06 in P2 during VM (area under ROC curve [AUROC] = 0.883 [0, 78, 0, 94]). There was a significant increase in AUROC (0.74 vs. 0.88, p = 0.006) during VM. For A/e' > 4.06, the sensitivity and specificity for DDII diagnosis were respectively 62% and 78% pre-VM and 85% and 78% during VM. CONCLUSIONS: Inversion of a pseudonormalized pulsed Doppler E/A ratio during VM has high sensitivity, but its low specificity makes it of little clinical use. An A/e' ratio > 4.1 during VM is a new, highly discriminative index that can be used in practice to diagnose LV grade II diastolic dysfunction in the presence of a pseudonormalized pulsed Doppler E/A ratio. PMID- 17849947 TI - Prevalence of microalbuminuria in non-diabetic hypertensive patients attended by Portuguese GPs. AB - OBJECTIVES: To determine the prevalence of microalbuminuria in a sample of non diabetic hypertensive patients and to correlate the presence of microalbuminuria with the patients' different clinical profiles. DESIGN: A descriptive, observational, cross-sectional and non-interventional enquiry based on strict respect for the standard general practitioner's medical practice and the physician-patient relationship. SETTING: Portuguese general practitioners (GPs) who had participated in a preliminary opinion survey on evaluation of renal function in hypertensive patients. POPULATION: Non-diabetic uncontrolled and controlled hypertensive patients. METHOD: Data were collected via written questionnaires completed by physicians at inclusion. Standard biochemical and microalbuminuria tests were performed by the laboratory chosen by each physician following the laboratory's usual practice. A Micral-Test"* to detect microalbuminuria was also performed on a spot morning urine collection. RESULTS: Between May and October 2003, 531 general practitioners recruited 1582 non diabetic hypertensive patients (58% female) with a mean age of 60.4 +/- 11.3 years; 11% of them were physically active and 10% were smokers. Almost all the patients (>95%) were under antihypertensive medication; 44% were also taking statins and 19% aspirin. Of the 1582 subjects, 57% (n=906) and 41% (n=652) had uncontrolled and controlled hypertension respectively, and 34% (n=539) had markers of renal function damage such as proteinuria, hematuria, microalbuminuria or albuminuria. Data for the Micral-Test were obtained in 98% of the patients and 29% (n=458) had a positive test. The mean albuminuria level was 12.34 +/- 37.88 mg/l. Seventy-six per cent of the patients (n=1196) had a normal urine test. Microalbuminuria was significantly more frequent in patients with uncontrolled (29%) than in controlled (20%) hypertension (p < 0.01), with left ventricular hypertrophy (LVH) (33%) than without (24%) (p < 0.01), with ventricular arrhythmias (35%) than without (25%) (p < 0.05) and with cerebral hemorrhage or transient ischemic attack (41%) than without (25%) (p < 0.001). CONCLUSION: This study confirmed that microalbuminuria is a powerful discriminator of high cardiovascular risk, and is associated with higher BP values and higher prevalence of LVH, ventricular arrhythmias and cerebrovascular disease in non diabetic hypertensive patients. PMID- 17849948 TI - Evaluation of systolic and systo-diastolic function: the Tei index in acute myocardial infarction treated with acute reperfusion therapy--early and late evaluation. AB - INTRODUCTION: Evaluation of systolic and diastolic function by non-invasive methods in the acute phase of myocardial infarction (MI) is of great importance for risk stratification and prognosis. Ejection fraction (EF), as determined by echocardiography using the Simpson method, is the main parameter for assessing left ventricular (LV) function. The Tei index (TI), a Doppler-derived index that reflects systolic and diastolic function in MI, has an excellent correlation with prognosis. OBJECTIVE: The purpose of this study was to evaluate systolic and systo-diastolic function in the acute and late phase of ST-elevation MI treated with acute reperfusion therapy. METHODS: Patients with ST-elevation MI who underwent acute reperfusion therapy were evaluated by echocardiography in the first 48 hours and after one week. The parameters studied were: EF, wall motion score index (WMSI), and TI. The values obtained at the first and second evaluation were compared and correlated with pain to reperfusion time (PRT) (<3 vs. > or =3 hours), presence of single or multivessel disease, ejection fraction, total CK (<1500 or > or =1500 UI/l), and MI location (anterior vs. other). RESULTS: 40 patients were studied and 19 were included, of whom 15 (80%) were male, mean age 57 +/- 14 years. Risk factors included hypertension (11 patients, 58%), smoking (14, 74%), diabetes (6, 30%), and dyslipidemia (12, 63%). MI location was anterior in 6 patients (32%) and inferior in 13 (68%). Five patients (26%) underwent fibrinolysis and 14 (74%) direct percutaneous coronary intervention. Mean pain to reperfusion time was 3.7 +/- 2.8 hours. Four patients (21%) had single vessel disease and 14 (74%) multivessel disease. Significant differences were found: (a) in mean EF and WMSI between the two evaluations (p < 0.0001 and p = 0.002 respectively); (b) between PRT and EF (p = 0.001) and WMSI (p = 0.020) at 48 hours; (c) between PRT and EF (p = 0.01) and TI (p = 0.033), and MI location and EF (p = 0.005) after one week. DISCUSSION AND CONCLUSIONS: Early systolic function and LV remodeling one week after MI were accurately evaluated by EF and WMSI. Early reperfusion therapy positively influences early and late systolic and systo-diastolic function. PMID- 17849949 TI - An unusual case of fungal endocarditis. AB - A case of fungal endocarditis in an unusual location is presented, in a patient with prolonged hospitalization due to extensive burns. The vegetations were located in the superior vena cava (probably adhering to a thrombus) at the site of a previous central venous catheter. The patient was treated with medical therapy only (voriconazole); after 5 months of therapy, she is without fever and transesophageal echocardiography shows that the thrombus and vegetations have disappeared. PMID- 17849950 TI - Prenatal diagnosis of congenital complete heart block. AB - Congenital complete heart block (CHB) is a conduction defect with an incidence in the general population of 1/15,000 to 1/22,000 live births. It is frequently associated with structural heart defects or maternal autoimmune disease. We describe a case of CHB associated with maternal systemic lupus erythematosus and review our previous cases and experience of CHB. PMID- 17849951 TI - Multiple complications of endocarditis. PMID- 17849952 TI - The effect of impact factor scores on the discipline of surgery. PMID- 17849953 TI - The 'modified triple staple' technique: a variant stapling technique for anastomosis after low anterior resection. AB - INTRODUCTION: Stapled techniques of coloanal anastomosis in anterior resection have gained widespread acceptance over hand anastomosis. We believe a modification of the 'triple staple technique' has ergonomic advantages over existing stapling methods and present our technique and experience here. METHODS: Fifty consecutive patients underwent anterior resection with a concomitant defunctioning ileostomy in 44 (86%) patients. A modified triple staple technique of side to end coloanal anastomosis was performed without the need of a purse string suture on the proximal and the distal segments. RESULTS: There were no major intra-operative complications. 2/50 (4%) clinical leaks and 2/37 (5.4%) radiological leaks were noted. A combined leak rate of 4/50 (8%) was reported. The incidence of anastomotic stricture encountered was 1/50 (2%). CONCLUSION: The modified triple staple technique for side to end anastomosis in anterior resection has ergonomic advantages and comparable safety to the existing techniques of stapling coloanal anastomosis. We believe this technique can be widely adopted as an added alternative to the current techniques of stapled anastomosis after anterior resection. PMID- 17849954 TI - Intramedullary reamings for the histological diagnosis of suspected pathological fractures. AB - The aim of this study was to evaluate how effective reamings taken at the time of surgery for fracture were in the diagnosis of malignancy. All histology reports over a five-year period were examined. Ninety cases, where reamings were taken, were identified and included. Reamings are commonly sent for histological diagnosis in orthopaedic practice. A definitive tissue diagnosis was established in 55 samples (60%). No diagnosis was established in 30 (33%), as the tissue sample was deemed inadequate, 17 of which were known to have a malignancy elsewhere. Five case reports were lost. The process by which the bone samples were obtained is believed to be very destructive, making histological diagnosis difficult and unreliable. Our study does not support the use of reamings for histology. An alternative technique should be used such as biopsy with the Harlow Wood trephine. PMID- 17849955 TI - Implications of sub-specialisation on the waiting times of general surgical clinics. AB - INTRODUCTION: Controversy around sub-specialisation in a district general hospital (DGH) has been ongoing for years. AIM: To study the effect of colorectal sub-specialisation on general surgical cases. METHODS: A retrospective audit between October 2002 and September 2003, including all referrals to the outpatient clinics of a single consultant surgeon in a DGH. RESULTS: 1,055 patients were seen in outpatient clinics, of which 53% (563) were seen in rapid access colorectal clinics. Overall, 87% (914) of patients were diagnosed to have colorectal pathology. The majority of the colorectal cases were referred using the designated referral forms. There were 427 urgent, 162 soon and 325 routine referrals with colorectal pathology, and 35 urgent, 22 soon and 84 routine referrals with non-colorectal pathology. Median waiting times for urgent, soon and routine referrals were 12, 61 and 91 days, respectively, for patients with colorectal pathology, in comparison with 44, 75 and 397 days for non-colorectal pathology. CONCLUSION: This audit confirms that colorectal sub-specialisation has resulted in a significant delay in the management of patients with non-colorectal diseases. This has major implications within a DGH setting. PMID- 17849956 TI - Routine laparoscopic repair of primary unilateral inguinal hernias--a viable alternative in the day surgery unit? AB - In September 2004 the NICE institute revised its guidelines on the management of primary inguinal hernias to include laparoscopic repair of unilateral hernias. While published trials have confirmed the equal efficacy of the two approaches, it is not clear what impact a switch to laparoscopic repairs would have on resources and patient throughput in a Day Surgery Unit. METHOD: All elective hernia repairs performed in a one-year period were considered. Data were obtained from operation notes, discharge summaries and out-patient records. Operating times are routinely documented in theatre. RESULTS: Of the 351 operations studied, 150 were performed laparoscopically predominantly by an extraperitoneal (TEP)approach. Six required conversion to an open procedure. There was no significant difference in operating times, total theatre time or recovery room times between the two groups (51 min, 75 min and 34 min for the laparoscopic group and 53 min, 74 min and 31 min for the open repair group). Among the laparoscopic repair group there were 48 bilateral hernias and 20 recurrent hernias while 190 of the 201 open repairs were for primary unilateral hernias. Rates of overnight stay and immediate complications were similar between the groups though haematoma was more common following open repair (7 vs 2). CONCLUSIONS: There is no difference in theatre times, immediate complication rates or rates of overnight stay between open and laparoscopic repair of inguinal hernia. Routine laparoscopic repair of primary unilateral inguinal hernia is a viable alternative within the Day Surgery Unit. PMID- 17849957 TI - Extremity amputation in Nigeria--a review of indications and mortality. AB - Amputation is a common surgical procedure in Nigeria but there are no national data on the subject. The objective was to determine the common indications for amputation in Nigeria, mortality rate, and regional differences in indications. Results of studies on amputation in Nigeria over a 15-year period were collated and analysed. The most frequent indications for amputation were trauma (34%); complication of traditional bonesetting (TBS) (23%); malignant tumours (14.5%); diabetic gangrene (12.3%); infections (5.1%); peripheral artery disease (2.1%); and burns (2.1%). In the southern regions, trauma is the most common indication while complications of traditional bonesetting are the most common in the northern and eastern regions. The average age of the Nigerian amputee is 33 years. Hospital mortality after amputation is 10.9%. The estimated prevalence of extremity amputation in Nigeria is 1.6 per 100,000. Peripheral artery disease is an uncommon indication for amputation in Nigeria while trauma, complication of traditional bonesetting, malignant tumours and diabetic gangrene are relatively much more common. The young male is frequently affected. PMID- 17849958 TI - Diabetic foot ulcers--a comprehensive review. AB - As the incidence of diabetes mellitus is increasing globally, complications related to this endocrine disorder are also mounting. Because of the large number of patients, foot ulcers developing in the feet of diabetics have become a public health problem. The predisposing factors include abnormal plantar pressure points, foot deformities, and minor trauma. Vulnerable feet usually already have vascular insufficiency and peripheral neuropathy. The complex nature of these ulcers deserves special care. The most useful prognostic feature for healing remains the ulcer depth, ulcers heal poorly if they clearly involve underlying tendons, ligament or joints and, particularly, when gangrenous tissue is seen. Local treatment of the ulcer consists of repeated debridement and dressing. No 'miraculous' outcome is expected, even with innovative agents like skin cover synthetics, growth factors and stem cells. Simple surgery like split skin grafting or minor toe amputations may be necessary. Sophisticated surgery like flap coverages are indicated for younger patients. The merits of an intact lower limb with an abnormal foot have to be weighed against amputation and prosthesis in the overall planning of limb salvage or sacrifice. If limb salvage is the decision, additional means like oxygen therapy, and other alternative medicines, might have benefits. The off-loading of footwear should always be a major consideration as a prevention of ulcer formation. PMID- 17849959 TI - On the transplantation, regeneration and induction of bone: the path to bone morphogenetic proteins and other skeletal growth factors. AB - The clinical and experimental transplantation of bone dates back to the seventeenth century and human allogeneic (homogeneic) bone has been successfully used as an alternative to autogenous bone since 1878, when Sir William Macewen reconstructed the right humerus of William Connell. This review describes how subsequent studies of bone transplantation led to the eventual discovery of a new family of secreted signalling molecules--the bone morphogenetic proteins (BMPs), and the realisation of the important role of polypeptide growth factors in mediating the growth, remodelling and regeneration of the skeleton. The development of suitable alternatives to both autogenous and allogeneic bone has been a goal of bone and biomaterials research for more than 30 years. The first requirement is a biocompatible, bioresorbable, osteoconductive framework supporting the ingrowth of host cells from the recipient bed. Many materials including collagen, calcium phosphate ceramics and synthetic polymers have been widely tested experimentally with varying success. The discovery of osteoinductive BMPs and their availability in recombinant human forms has given considerable impetus to the field. However, progress to date in engineering significant quantities of functional bone tissue in vivo has been disappointing; finding suitable carriers for BMPs has proven to be a greater challenge than expected. The dilemma for the clinician and the biotechnology industry, at present, is that, while recombinant human growth factors are readily available for clinical use, the lack of delivery systems that can adequately mimic both the physical properties and release kinetics of bone matrix remains a major handicap. PMID- 17849960 TI - Totally extra-peritoneal repair of inguinal hernia by a glove-balloon: technical innovation. AB - Totally extra-peritoneal (TEP) laparoscopic repair of an inguinalhernia involves the creation of an extra-peritoneal space by blunt dissection or the use of commercial balloons. This new technique demonstrates the use of a device to create this extra-peritoneal space, without the need for any commercial balloons. The extra-peritoneal space was created using a glove-balloon. A total of 107 consecutive TEP repairs were carried out using the glove-balloon technique, these included ten bilateral and 17 recurrent inguinal hernias. This method is simple, cost-effective and easy to teach. PMID- 17849961 TI - Primary squamous cell carcinoma of the thyroid gland: a case report and role of radiotherapy. AB - Primary squamous cell carcinoma is an extremely rare tumour of the thyroid gland. A case of an elderly lady who was diagnosed to have primary squamous cell carcinoma of the thyroid gland is presented and the role of radiotherapy is discussed. PMID- 17849962 TI - Re: J.M. Rehman, C.S. Seow, P.J. O'Dwyer. A case of Spigelian hernia at an unusually high anatomical location. J. R. Coll. Surg. Edin. 2000, 46;2: 196-97. PMID- 17849964 TI - Win-win-win. PMID- 17849963 TI - Re: Street et al. Audit of nasendoscope disinfection practice. Surgeon 2006, 4;1: 11-13. PMID- 17849965 TI - Articaine versus lidocaine: the author responds. PMID- 17849966 TI - The burning mouth. AB - Burning in the mouth in and of itself is not all that uncommon. It may result from a variety of local or generalized oral mucosal disorders, or may be secondary to referred phenomena from other locations. Primary burning mouth syndrome, on the other hand, is relatively uncommon. Burning mouth syndrome is an idiopathic pain disorder, which appears to be neuropathic in origin. Thoughts on management of secondary and particularly primary burning mouth syndrome are discussed. PMID- 17849967 TI - Diagnosis and management of oral lichen planus. AB - Oral lichen planus is a relatively common mucosal autoimmune disease that may be initially detected and diagnosed in the dental office. For asymptomatic patients, clinical characteristics including a generalized involvement of the oral mucosa are often sufficient to establish a working diagnosis. Symptomatic presentations of oral lichen planus, however, can mimic a variety of other potentially serious conditions and scalpel biopsy is recommended to determine an accurate diagnosis. Treatment strategies for the symptomatic patient are discussed. PMID- 17849968 TI - Diagnosis and management of oral lichenoid reactions. AB - Lichen planus is one of the most common mucocutaneous conditions seen in dental practice. A variety of other conditions known as lichenoid reactions can simulate lichen planus either clinically or histologically. This paper will discuss the more common lichenoid reactions seen in clinical practice and review the diagnosis and management of these conditions. PMID- 17849969 TI - Dental management of xerostomia--opportunity, expertise, obligation. AB - Xerostomia often goes undiagnosed and unmanaged. Failure to properly deal with this condition leaves patients at greater risk for other problems. Dentists have the opportunity, the expertise, and the obligation to identify and manage xerostomia and its complications. This article presents a practical approach to diagnosis and treatment of xerostomia and its complications. PMID- 17849970 TI - Open wide: here comes IntelliDrug. PMID- 17849971 TI - Anaerobic treatment of vinasses by a sequentially mixed moving bed biofilm reactor. AB - Wine distillery wastewater, commonly called vinasses, was treated by an anaerobic moving bed biofilm reactor (AMBBR) with 32.9 litre available volume. The reactor was filled with 66% cylindrical polyethylene supports with density 0.84 g cm(-3) as a biofilm carrier. The reactor was sequentially mixed by a submerged centrifugal pump fixed to the bottom, and each mixing time just lasted 1.25 minutes. The organic loading rate (OLR) of the reactor were increased from 1.6 to 29.6 g sCOD l(-1) d(-1) (soluble chemical oxygen demands--sCOD) and hydraulic retention time (HRT) was decreased from 6.33 to 1.55 days accordingly. Soluble COD removal efficiency was 81.3-89.2% at an OLR of 29.6 g sCOD l(-1) d(-1). At the end of the experiment, 83.4% total biomass was attached on support and the specific density of support in the reactor was 0.93-1.05 g cm(-3), which increased by about 10.7-25% compared with that at the beginning of the study. PMID- 17849972 TI - Treatment of wine distillery wastewater by high rate anaerobic digestion. AB - Wine distillery wastewaters (WDW) are acidic and have a high content of potential organic pollutants. This causes high chemical oxygen demand (COD) values. Polyphenols constitute a significant portion of this COD, and limit the efficiency of biological treatment of WDWs. WDW starting parameters were as follows: pH 3.83, 4,185 mg/l soluble COD (COD(s)) and 674.6 mg/l of phenols. During operation, amendments of CaCO3 and K2HPO4, individually or in combination, were required for buffering the digester. Volatile fatty acid concentrations were < 300 mg/l throughout the study, indicating degradation of organic acids present. Mean COD(s) removal efficiency for the 130 day study was 87%, while the mean polyphenol, removal efficiency was 63%. Addition of 50 mg/l Fe(3+) between days 86 and 92 increased the removal efficiencies of COD(s) to 97% and of polyphenols to 65%. Addition of Co(3+) improved removal efficiencies to 97% for COD(s) and 92% for polyphenols. Optimization of anaerobic treatment was achieved at 30% WDW feed strength. Removal efficiencies of 92% and 84% were recorded at increased feed strength from days 108 to 130. High removal efficiencies of COD(s) and polyphenols after day 82 were attributed to the addition of macronutrients and micronutrients that caused pH stability and thus stimulated microbial activity. PMID- 17849973 TI - Treatment of distillery vinasse in a high rate anaerobic reactor using low density polyethylene supports. AB - An anaerobic fixed bed reactor, filled with small floating supports of polyethylene material (Bioflow 30) as inert media, was operated for 6 months to treat vinasse (wine residue after distillation). Bioflow 30 has a density of 0.93 and a specific area of 320 m2/m3. The experimental results showed that the efficiency of the reactor in removal of soluble COD was very good with a maximum organic loading rate of more than 30 g of COD/L x d and a COD removal efficiency of more than 80%. Bioflow 30 showed a high capability of biomass retention with 4 6 g of dried solids per support. Thus, at the end of the experiment, the fixed biomass represented 57 g of solids/L of reactor. The visual observation of the supports and the specific activity (0.54 g COD/g solids x d) of the fixed solids, which remained close to the values obtained with suspended biomass, showed that entrapment was playing an important role in the retention of the biomass inside the reactor. It was then possible to operate the reactor with a very high loading rate as the result of the increase of the solids in the reactor and the maintaining of the specific activity. Bioflow 30 is then an excellent support for use in a high rate anaerobic fixed bed. PMID- 17849974 TI - Winery effluent treatment at an anaerobic hybrid USBF pilot plant under normal and abnormal operation. AB - A 1.1 m3 hybrid USBF fully instrumented pilot plant has been used for the treatment of diluted wine for four years. In this work, the performance of the wastewater treatment plant (WWTP) during start up and operation (normal operation and overload experiments) is shown. A complete description of the treatment process behaviour (gas and liquid phase composition and anaerobic sludge characteristics) is given by on-line and off-line monitoring of 28 process variables. The results presented here demonstrate the reliability of this technology for the treatment of wastewater from seasonal processes, such as winery wastewaters, during a long period of time (four years). Furthermore, the USBF reactor presented very short start up periods after short and long shut down of the WWTP and rapidly turned back to normal operation after suffering a complete destabilization due to organic overload. Both effluent and biogas were of good quality. Dissolved organic carbon concentration in the effluent was always lower than 100 mg DOC l(-1) under normal operation, while methane concentration in the biogas was in the range 70-74%, making it suitable for energy recovering. PMID- 17849975 TI - Anaerobic fluidized bed reactor application to tropical fruit wine effluent. AB - The influence of the organic loading rate (OLR), the fluidization level (FL) and the particle diameter of natural zeolite used as support (D(p)), was evaluated at a laboratory scale anaerobic fluidized bed reactor (AFBR), treating tropical fruit wine effluent (vinasse). The experiment was carried out at an OLR from 2-5 kg COD/m3 d, FL of 20 and 40% and D(p) from 0.25 to 0.80 mm. It was demonstrated that OLR and FL had a slight influence on chemical oxygen demand removal and strong influence on the methane production rate. The COD removal was slightly higher for the higher particle diameter used. Additionally using the scanning electron microscope (SEM), it was observed that natural zeolites have excellent physical characteristics as a support medium in AFBR. PMID- 17849976 TI - Selected experiences in Chile for the application of UASB technology for vinasse treatment. AB - One of the research areas is the agricultural use of treated wastewaters, because it represents a unique opportunity to solve the problem of water supply for irrigation and at the same time the disposal of treated water. Anaerobic digestion appears as an interesting alternative, since anaerobically treated wastewaters can be used for irrigation purposes. These considerations are applied to the Chilean pisco industry (a traditional alcoholic drink, prepared by distillation of wine made mainly from Muscatel grapes), where high concentrated wastewaters are produced: vinasses originate as a residue from the distillation operation. Two laboratory reactors fed with wine vinasses, a UASB and an EGSB, were used in order to study the anaerobic treatability of the wastewater. Then, a pilot reactor was built (60 m3 UASB digester) and treated water was used to irrigate eucalyptus trees. Finally a 300 m3 reactor, including biogas treatment for its reuse, was developed. Results showed, both at laboratory and full scale, that anaerobic treatment is suitable for pisco's wastewaters, and also that the nutrient content of treated water can be beneficial for plant growth, reducing the need for fertilizers. Another kind of investigation was carried out in order to study the stability of anaerobic granules and how it can be recovered. UASB and EGSB were fed with low, medium and high load wastewaters, in order to evaluate possible fluctuations in the productive process. From these results, it was possible to propose and to apply recovery techniques to the digesters when they are destabilized. PMID- 17849977 TI - Anaerobic co-digestion of winery wastewater. AB - The operational performance of anaerobic batch reactors treating winery wastewater (WW) combined with waste activated sludge (WAS) in different proportions was investigated under mesophilic conditions. In these experiments it was shown that for anaerobic digestion of WW alone, methane production rate was lower than the rates achieved when WW and WAS were treated together. When WW was mixed with WAS at a concentration of 50% WW resulted in the highest methane production rates. A simplified anaerobic model was used to determine the main kinetic parameters; maximum COD reduction rate (q(DA)) and maximum methane generation rate (k(max)). The maximum values of q(DA) and k(max) were 16.50 kgCOD COD(-1) d(-1) and 14.34 kgCOD kgCOD(-1) d(-1), respectively. PMID- 17849978 TI - Assessing the degradation of ochratoxin a using a bioassay: the case of contaminated winery wastewater. AB - In vineyards the presence of certain fungi may lead to the production of the mycotoxin ochratoxin A (OTA) and subsequent contamination of grapes and wine. Furthermore, winery wastewaters contaminated with OTA may represent an environmental hazard. Therefore, it is imperative to assess the fate of this mycotoxin in conventional wastewater treatment systems. The aim of the present work was to assess the biological degradation of OTA. Experimental work was carried out in batch experiments with initial OTA to biomass concentration ratios of 1.4 microg mg(-1), 7.4 microg mg(-1) and, 11.9 microg mg(-1). The assays were inoculated with activated sludge biomass unadapted to the substance under examination. The proposed bioassay demonstrates that OTA concentrations up to 100 microg L(-1) can be degraded by microbial activity in activated sludge. PMID- 17849979 TI - Treatment of winery wastewaters in a membrane submerged bioreactor. AB - Wine production is seasonal, and thus the wastewater flow and its chemical oxygen demand (COD) concentrations greatly vary during the vintage and non-vintage periods, as well as being dependant on the winemaking technologies used, e.g. red, white or special wines production. Due to this seasonal high variability in terms of organic matter load, the use of membrane biological reactors (MBR) could be suitable for the treatment of such wastewaters. MBR offers several benefits, such as rapid start up, good effluent quality, low footprint area, absence of voluminous secondary settler and its operation is not affected by the settling properties of the sludge. A pilot scale hollow fibre MBR system of 220 L was fed by adequately diluting white wine with tap water, simulating wastewaters generated in wineries. The COD in the influent ranged between 1,000 and 4,000 mg/L. In less than 10 days after the start up, the system showed a good COD removal efficiency. The COD elimination percentage was always higher than 97% regardless of the organic loading rate (OLR) applied (0.5-2.2 kg COD/m3 d), with COD concentrations in the effluent ranging between 20 and 100 mg/L. Although the biomass concentration in the reactor increased from 0.5 to 8.6 g VSS/L, the suspended solids concentration in the effluent was negligible. Apparent biomass yield was estimated in 0.14 g VSS/g COD. PMID- 17849980 TI - Continuous and sequencing membrane bioreactors applied to food industry effluent treatment. AB - This work focuses on the performances of two immersed membrane bioreactors used for the treatment of easily biodegradable organic matter present in food industry effluents, for the purpose of water reuse. Two reactor functioning modes (continuous and sequencing) were compared in terms of organic carbon removal and of membrane permeability. For each working mode, pollutant removal was very high, treated water quality presented a low COD concentration (< 125 mg x L(-1)), no solids in suspension and low turbidity (< 0.5 NTU). The quality of the treated water (including germ removal) enabled its reuse on site. Moreover, by developing high biomass concentrations in the reactor, excess sludge production remained very low (< 0.1 gVSS x gCOD(-1)). The performances appeared slightly better for the continuous system (lower COD concentration in the effluent, < 50 mg x L(-1), and lower sludge production). In terms of filtration, a distinct difference was observed between continuous and sequencing systems; transmembrane pressure showed a small and constant evolution rate in continuous membrane bioreactor (CMBR) although it appeared more difficult to control in sequencing membrane bioreactor (SMBR) probably due to punctually higher permeate flow rate and modified suspension properties. The rapid evolution of membrane permeability observed in SMBR was such that more frequent chemical cleaning of the membrane system was required. PMID- 17849981 TI - Treatment of winery wastewater in a conventional municipal activated sludge process: five years of experience. AB - A full-scale wastewater treatment plant where municipal and winery wastewaters were co-treated was studied for five years. The experimental results showed that suspended solids, COD, nitrogen and phosphorous were effectively removed both during the treatment of municipal wastewater and the cotreatment of municipal and winery wastewater. The sludge production increase from 4 tons to 5.5 tons per day during the harvesting and wine making period. In any case the specific sludge production was 0.2 kgMLVSS per kgCOD(removed) despite the organic loading increasing. About 70% of the COD was removed through respiration. Also the energy demand increased from 6,000 to 7,000 kWh per day. The estimated costs for the treatment of the winery wastewater was 0.2-0.3 Euros per m3 of treated wastewater. With reference to the process efficiency, the nitrogen removal was just 20%. The co-treatment of municipal and winery wastewater in conventional activated sludge processes can be a feasible solution for the treatment of these streams at relatively low costs. PMID- 17849982 TI - Photo-Fenton processes assisted by solar light used as preliminary step to biological treatment applied to winery wastewaters. AB - Winery wastewaters are difficult to treat by conventional biological processes, because they are seasonal and experience substantial flow variations. Photocatalytic advanced oxidation is a promising technology for wastewaters containing high amounts of organic matter. In this research work, solar assisted photo-Fenton processes of both heterogeneous and homogeneous phase are used in the pre-treatment of winery wastewaters. The results of these experiments have confirmed the suitability of the photo-Fenton processes, due to these treatments achieving purification levels of up to 50% (measured as total organic carbon). The intermediate effluents are treated adequately by aerobic biological treatment (activated sludge process), due to the decrease in organic matter concentration present in winery wastewaters. The possibility of a combined photo-Fenton process, based on the use of sunlight, and aerobic biological treatment (activated sludge) is suggested. PMID- 17849983 TI - Re-use of winery wastewaters for biological nutrient removal. AB - The aim of this study was to evaluate the feasibility of the re-use of the winery wastewater to enhance the biological nutrient removal (BNR) process. In batch experiments it was observed that the addition of winery wastewater mainly enhanced the nitrogen removal process because of the high denitrification potential (DNP), of about 130 mg N/g COD, of the contained substrates. This value is very similar to that obtained by using pure organic substrates such as acetate. The addition of winery wastewater did not significantly affect either phosphorus or COD removal processes. Based on the experimental results obtained, the optimum dosage to remove each mg of N-NO3 was determined, being a value of 6.7 mg COD/mg N-NO3. Because of the good properties of the winery wastewater to enhance the nitrogen removal, the viability of its continuous addition in an activated sludge pilot-scale plant for BNR was studied. Dosing the winery wastewater to the pilot plant a significant increase in the nitrogen removal was detected, from 58 to 75%. The COD removal was slightly increased, from 89 to 95%, and the phosphorus removal remained constant. PMID- 17849984 TI - Winery wastewater treatment by constructed wetlands and the use of treated wastewater for cash crop production. AB - A 45 m long, 4 m wide and 1 m deep wetland was constructed at Goudini in 2002 to treat distillery and winery effluent. After the plants were fully established, the wastewater with an average chemical oxygen demand (COD) of 14,000 mg/l was introduced to the wetland system at a rate of 4,050 litres per day. After treatment, wastewater at the outlet had an average COD of 500 mg/l, indicating more than 90% COD removal. After treatment, the wastewater was used to irrigate cash crops as part of poverty alleviation for farm workers. The experiment consisted of four treatment: clean irrigation water with fertilizer applied (B1); clean irrigation water without fertilizer applied (B2); wastewater irrigation with fertilizer applied (B3); and wastewater irrigation without fertilizer applied (B4). These were replicated seven times. Cabbage was cultivated as a cash crop. The results indicated that cabbage could be irrigated with winery wastewater treated by wetlands. The study found that there was significant difference between treatments that were fertilized compared with those that were not fertilized. The results indicated that wastewater irrigation improved the nutritional status of the soil. PMID- 17849985 TI - Heavy metal removal from winery wastewater in the case of restrictive discharge regulation. AB - In most cases of winery effluent, the heavy metal content, especially zinc (Zn) and copper (Cu), does not meet the limits for the discharge as imposed by the most restrictive regulations at international level (0.4 mgCu/L and 1.0 mgZn/L in the Italian regulations). An alternative for the reduction of Cu and Zn is the on site pre-treatment of wastewater at the winery in order to meet the limits for the discharge into the public sewerage. The purpose of this study is to evaluate the effectiveness of a pre-treatment based on chemical precipitation with chelating agents (TMT: 2,4,6-trimercaptotriazine), for the reduction of Cu and Zn from raw winery wastewater. The chemical precipitation was optimised at lab-scale through jar tests in order to evaluate the optimal dosages. An average dosage equal to 0.84 mL of TMT (15%) for 1 mg of Cu removed was estimated. Furthermore, the efficiency of the on-site chemical pre-treatment was investigated at pilot scale. The results confirmed the feasibility of using TMT treatment for the reduction of Cu and Zn in order to meet the limits for discharge into the sewerage. Contextually to the removal of heavy metals, the chemical pre-treatment allowed us to obtain the reduction of particulate COD and TSS. Finally, the costs for the operation and the management of the on-site pre-treatment were evaluated. PMID- 17849986 TI - Characterization, management and treatment of wastewater from white wine production. AB - During a 16 months period, the characteristics of the wastewaters generated in a Rias Baixas winery (Spain) producing white wine were determined: The characterization study showed that white wine wastewater had an average CODt and TSS values of 7.3 and 5.2 kg/m3, respectively being the ratio wastewater/wine produced of about 1.6-2.0 L/L and the ratio between load pollution and produced wine of 9.7 kg(CODt)/m3(WINE). A strategy for the management of wastes and wastewaters allowed for an important reduction of a 55% of wastewater generation to be achieved. In order to select a suitable technology for the treatment of wastewaters two configurations were tested at pilot scale: i) An Anaerobic Filter (AF) of 430 L followed by an activated sludge unit of 510 L and: ii) one activated sludge unit of 510 L. The results showed that the anaerobic/aerobic configuration was more flexible as it adapted quickly to the different loads and flows produced during the different phases through the year. Besides it allowed higher COD removals (98.5-99.2%) to be achieved and proved to permit a quicker re start up after starvation periods. PMID- 17849987 TI - Evaluation of rapid methods for in-situ characterization of organic contaminant load and biodegradation rates in winery wastewater. AB - Rapid methods for the in-situ evaluation of the organic load have recently been developed and successfully implemented in municipal wastewater treatment systems. Their direct application to winery wastewater treatment is questionable due to substantial differences between municipal and winery wastewater. We critically evaluate the use of UV-VIS spectrometry, buffer capacity testing (BCT), and respirometry as rapid methods to determine organic load and biodegradation rates of winery wastewater. We tested three types of samples: actual and treated winery wastewater, synthetic winery wastewater, and samples from a biological batch reactor. Not surprisingly, respirometry gave a good estimation of biodegradation rates for substrate of different complexities, whereas UV-VIS and BCT did not provide a quantitative measure of the easily degradable sugars and ethanol, typically the main components of the COD in the influent. However, our results strongly suggest that UV-VIS and BCT can be used to identify and estimate the concentration of complex substrates in the influent and soluble microbial products (SMP) in biological reactors and their effluent. Furthermore, the integration of UV-VIS spectrometry, BCT, and mathematical modeling was able to differentiate between the two components of SMPs: substrate utilization associated products (UAP) and biomass associated products (BAP). Since the effluent COD in biologically treated wastewaters is composed primarily by SMPs, the quantitative information given by these techniques may be used for plant control and optimization. PMID- 17849988 TI - Selection of variables using factorial discriminant analysis for the state identification of an anaerobic UASB-UAF hybrid pilot plant, fed with winery effluents. AB - Anaerobic wastewater treatment has become a widely used method for wastewater depuration, and has been applied in a wide range of situations, from urban wastewater to highly toxic industrial wastewater. Particularly it has been successfully applied to the treatment of the beverage industries effluents. To avoid the destabilization of the system a monitoring diagnosis and control system of the depuration processes is necessary. The cost of this system is an important issue, that depends on the number of parameters that must be controlled for an adequate performance of a wastewater plant control system. This work shows how the classic statistical classification techniques can be applied to determine the number variables that must be monitored to achieve an adequate performance of anaerobic UASB-UAF hybrid Pilot Plant monitoring and control system. The obtained results had not been unique, so different combinations of variables can be selected for a good wastewater treatment process control. Economic or technical criteria may be considered to determine the final variables set in each particular situation. PMID- 17849989 TI - Use of modelling to evaluate best control practice for winery-type wastewaters. AB - Winery wastewaters are high strength, and readily biodegradable, making them perfect for application of anaerobic digestion. However, inherent buffering against pH changes also requires some process knowledge and monitoring. They are therefore an important target for anaerobic process control. This has had limited application, but is emerging as an important research and development area. In this paper, we evaluate the use of model-based control analysis of a heavily loaded vinasse-fed reactor. Two controllers--both proportional-integral (PI)--on total volatile fatty acids (VFA) (< 500 mg/L), alkalinity (VFA/Total Alkalinity < 0.2) were evaluated in a fitted model, against the actual control mechanism used, which was model-based adaptive control. The two controllers were both less aggressive than the adaptive controller, producing less gas overall, but also using more caustic for pH control. The controllers were also evaluated against their ability to deal with noise, as PI controllers are relatively poor for controlling non-linear processes. The VFA controller was very poor with noise added, proving difficult to tune, and oscillatory. The alkalinity controller was effective with moderate detuning. This emphasizes the need to use effective controller inputs, when applying simple, linear controllers. Overall, use of a model was an effective method to evaluate the different controllers in a competitive way, in a standardized environment. PMID- 17849990 TI - Towards a benchmarking model for winery wastewater treatment and disposal. AB - We propose a benchmarking model for winery wastewater treatment systems and use it to quantitatively compare the performance of Chilean wine-making operations. The benchmarking model integrates three components: the influent characteristics, the wastewater treatment alternatives, and the location constraints. Four performance levels may be defined when plotting the available data of the wine production versus the ratio of wastewater to wine, for the French, US, and Chilean industries. Knowing where a certain system lies in this diagram helps to quantify the gap between the current and a target performance, and to set performance goals for planned expansions. The analysis of construction and operating costs of treatment systems currently in operation in Chile shows that similar compliance levels can be achieved at remarkably different costs. A steep decrease in the unitary cost is observed as wastewater flow increases; yet, the treatment alternative for achieving that cost may change. Further selection is obtained when location constraints are considered, including stringent discharge standards and proximity to urban settlements. The application of this simple benchmark model to three Chilean winery facilities shows how it produces meaningful quantitative and qualitative results. However, there is still ample room to improve this benchmarking model by considering additional complexity, including technical detail in the treatment options and costs related to technology conversion. PMID- 17849991 TI - The impact of CCA-treated posts in vineyards on soil and ground water. AB - Grapes in Marlborough are typically grown on a vertical shoot positioned trellis system (VSP). For this purpose Pinus radiata posts are treated with CCA, a mixture of copper (Cu), chromium (Cr) and arsenic (As), giving a wood concentration of 1,730, 3,020 and 2,410 mg/kg, respectively on a dry matter basis. The CCA levels around the posts in different soils were investigated and assessed for the potential leaching of CCA into ground water. An initial survey showed leaching of all three heavy metals from the treated posts into the soil surrounding the posts (0.2% of the total vineyard area) compared with the control, depending on vineyard age and soil type. The rate of movement out of the posts was calculated from posts placed in lysimeters. HortResearch's Soil Plant Atmosphere Model (SPASMO) was used to predict the leaching rate of CCA. For As, leaching was found to be 5 mg/post/month, with the Cr rate being about twice that. Further modelling revealed a steady plume of As moving downwards after about 200-300 years. However, long-term hydrogeological modelling showed that sufficient aquifer water flow prevented the accumulation of CCA in the ground water. The modelling approaches are discussed. PMID- 17849992 TI - Evaluation of six pesticides leaching indexes using field data of herbicide application in Casablanca Valley, Chile. AB - A field study was performed to evaluate the accuracy of six pesticide screening leaching indexes for herbicide movement. Adsorption, dissipation and soil movement were studied in a vineyard in a sandy loam soil during 2005 season. Simazine, diuron, pendimethalin, oxyfluorfen and flumioxazin were applied to bare soil at rates commonly used, and their soil concentrations throughout soil profile were determined at 0, 10, 20, 40 and 90 days after application (DAA). Herbicides were subjected to two pluviometric regimens, natural field condition and modified conditions (plus natural rainfall 180 mm). Leaching indexes utilized were: Briggs's Rf, Hamaker's Rf, LEACH, LPI, GUS and LIX. Simazine reached 120 cm, diuron 90 cm, flumioxazin 30 cm soil depth respectively. Pendimethalin and oxyfluorfen were retained up to 5 cm. None of the herbicides leaching was affected by rainfall regimen. Only flumioxazin field dissipation was clearly affected by pluviometric condition. The best representation of the herbicide soil depth movement and leaching below 15 cm soil depth were: Hamaker's Rf < Briggs's Rf < GUS < LPI, < LEACH < LIX. Field results showed a good correlation between herbicides K(d) and their soil depth movement and mass leached below 15 cm soil depth. PMID- 17849993 TI - Bioremediation of a wine distillery wastewater using white rot fungi and the subsequent production of laccase. AB - The aim of this work was to ascertain whether a submerged culture of a white rot fungus could be used to treat distillery wastewater, and whether the compounds present in the wastewater would stimulate laccase production. Trametes pubescens MB 89, Ceriporiopsis subvermispora, Pycnoporus cinnabarinus and UD4 were screened for their ability for the bioremediation of a raw, untreated distillery wastewater as well as distillery wastewater that had been pretreated by polyvinylpolypyrrolidone. Suitability of each strain was measured as a function of decreasing the chemical oxygen demand (COD) and total phenolic compounds concentration and the colour of the wastewater, while simultaneously producing laccase in high titres. After screening, T. pubescens MB 89 was used further in flask cultures and attained 79 +/- 1.1% COD removal, 80 +/- 4.6% total phenols removal, 71 +/- 1.6% decrease in colour at an absorbance of 500 nm and increased the pH from 5.3 to near-neutral. Laccase activity in flask cultures peaked at 4,644 +/- 228 units/l, while the activity in a 50 l bubble lift reactor peaked at 12,966 +/- 71 units/l. Trametes pubescens MB 89 greatly improved the quality of a wastewater known for toxicity towards biological treatment systems, while simultaneously producing an industrially relevant enzyme. PMID- 17849994 TI - Co-composting of distillery and winery wastes with sewage sludge. AB - The winery and distillery wastes (grape stalk and marc (GS and GM, respectively), wine lees (WL) and exhausted grape marc (EGM)) are produced in great amounts in the Mediterranean countries, where their treatment and disposal are becoming an important environmental problem, mainly due to their seasonal character and some characteristics that make their management difficult and which are not optimised yet. Composting is a treatment widely used for organic wastes, which could be a feasible option to treat and recycle the winery and distillery wastes. In this experiment, two different piles (pile 1 and 2) were prepared with mixtures of GS, GM, EG and sewage sludge (SS) and composted in a pilot plant by the Rutgers static pile composting system. Initially, GS, GM and EGM were mixed, the pile 1 being watered with fresh collected vinasse (V). After 17 days, SS was added to both piles as a nitrogen and microorganisms source. During composting, the evolution of temperature, pH, electrical conductivity, total organic C, total N, humic acid-like C and fulvic acid-like C contents, C/N ratio, cation exchange capacity and germination index of the mixtures were studied. The addition of V in pile 1 produced higher values of temperature, a greater degradation of the total organic C, higher electrical conductivity values and similar pH values and total N contents than in pile 2. The addition of this effluent also increased the cation exchange capacity and produced a longer persistence of phytotoxicity. However, both piles showed a stabilised organic matter and a reduction of the phytotoxicity at the end of the composting process. PMID- 17849995 TI - College faces toughest decision in its history. PMID- 17849996 TI - 'The NHS may get the best deal on its housekeeping but at what cost to care'? PMID- 17849997 TI - Overhauling nurse careers. What you think. PMID- 17849998 TI - Nursing the victims of gun crime. PMID- 17849999 TI - Improving mental health services for older people. PMID- 17850000 TI - Respiratory procedures. Part 3--use of a nebuliser. PMID- 17850001 TI - Palliative care emergencies. 2: Management. AB - This is the second of a two-part unit on palliative care emergencies. The first part looked at the signs and symptoms of conditions classed as palliative care emergencies. This part examines treatment regimens and related nursing care to ensure patient safety and comfort. PMID- 17850002 TI - [Between calm and frenzy there is, as Horace said. a "middle ground", a medium mor precious than gold]. PMID- 17850003 TI - [High-altitude related illness]. AB - Development of modern tourist industry facilitates access to high altitude for a growing population of non-acclimatized individuals who frequently are unaware of the hazards related to this environment, which is characterized by low ambient oxygen due to low atmospheric pressure. High-altitude related illnesses therefore represent an emerging medical issue, which may become of concern for every practitioner. Three clinical entities are classically described: acute mountain sickness (AMS), high altitude cerebral edema (HACE) and high altitude pulmonary edema (HAPE), the two latter representing vital emergencies. The present paper presents the current recommendations for their diagnostic, prophylactic and therapeutic management. PMID- 17850004 TI - [Autologous chondrocyte implantation for focal cartilage lesions: state of the art in 2007]. AB - Autologous chondrocyte implantation (ACI) is a frequently used procedure for full thickness cartilage lesions in the knee joint. However, to date, there are just a few prospective, randomized clinical studies and most publications are case series on small and heterogenic cohorts with short-term follow-up. To date, ACI is a surgical treatment option for single traumatic lesions on the distal femur in young active subjects with a recent lesion. Lesion size should be between 3 and 8 cm2, < 6 mm in depth, tidemark preserved without penetration of the subchondral bone. Absolute contraindications for ACI include osteoarthrosis, kissing lesions, lesions size greater than 10 cm2 or deeper than 8 mm, ligament instability, partial or total meniscectomy, axis malalignment > 5. Further studies are mandatory to determine the precise indications to the technique and to show its superiority on the established treatment of chondral lesions. PMID- 17850005 TI - [Inguinal pain in sportmen: clinical and radiological examinations]. AB - Pain of the inguinal region is a frequent but difficult diagnostic problem. It may be induced by accidents, overload due to sports or profession as well as daily life activities. Numerous anatomic structures of the inguinal or hip region may be injured, but one should also think about adjacent structures as the bowel, uro-genital system, spine and nerves. The goal of this article is to describe which clinical and imaging parameters allow to establish a correct diagnosis for each patient. PMID- 17850006 TI - [Groin pain in athletes]. AB - Groin pain is a common problem in athletes who engage in sports involving accelerations, decelerations and sudden direction changes. It is still a frustrating pathology which has significant overlap and multiple problems coexist frequently. The pathogeny remains unclear, but the hypothesis that imbalances between abdominal muscles and adductors exist, has a certain success. Some anatomic and biomechanic factors may play a role in this pathology. A good clinical examination is an important part of the diagnosis and imaging may be helpful to eliminate other causes of groin pain that wouldn't be mechanic. The conservative treatment is long and difficult and must be focused on functional strengthening and core stabilisation. PMID- 17850007 TI - [Tendinopathies: the most effective physiotherapeutic treatments]. AB - Tendinopathy, a current injury often falsely named tendinitis, is a lesion due to an excess load of the tendon with impairment of its collagen fibers. The repair of tendinous fibers requires many weeks; the treatment is a determining factor. There are numerous physiotherapy treatments. We have chosen the most usual ones, controlled their evidence of effectiveness according to the literature and shown which techniques with proven efficacy should be used in every tendinopathy treatment: cold, stretching, eccentric training. If these give no satisfactory results, shock waves could be useful. Ultrasonic therapy is worthless although widely used. Serious studies on other techniques are lacking. An evidence based physiotherapy is of prime importance for the future. PMID- 17850008 TI - [Symptomatic treatment of non-displaced avulsion and Jones fractures of the fifth metatarsal: a prospective study]. AB - The objective was to compare the results of a conservative treatment of non displaced Jones fractures and of avulsion fractures of the fifth metatarsal. In 2004/2005 29 fractures of the fifth metatarsal were distinguished into avulsion fractures (n = 21) and Jones fractures (n =8). Six patients with avulsion fractures were lost. We proposed the same treatment for the two groups: Elastic banding, pain killers, crutches if needed and thromboembolic prophylaxis with low molecular heparin. After twelve weeks none of the patients complained about pain. Radiographic consolidation of the fracture was noticed after 7.3 weeks for the Jone's fractures and after 7.1 weeks for the avulsion fractures. We propose symptomatic treatment for the non-displaced avulsion and Jones fractures. PMID- 17850009 TI - [Ceervicobrachial pain: what is the cause? (2). The view of the neurosurgeon]. PMID- 17850010 TI - [The nobility of the comma]. PMID- 17850011 TI - [An almost typical couple]. PMID- 17850012 TI - [Tracking down the possibility of prostatic cancer]. PMID- 17850013 TI - [Termination because of genetic susceptibility]. PMID- 17850014 TI - [Grief from recent lessons from Tripoli]. PMID- 17850015 TI - [The spirit of conquest]. PMID- 17850016 TI - [On the role of brain serotonin system in the pathway from gene to behaviour]. AB - This paper concentrates on involvement of protein elements in the brain neurotransmitter serotonin system (key enzymes in serotonin metabolism and 5 HT(1A) receptors) in the genetic control of behaviour. The data were obtained using Norway rats selected for more that 50 generations for lack of aggressive response and for aggressive behaviour towards humans (fear-induced aggression), inbred mouse strains, and MAO A knockout mice. The review provides converging line of evidence that: 1) brain serotonin contributes to critical mechanism underlying genetically defined individual differences in aggressiveness, and 2) genes encoding pivotal enzymes in serotonin metabolism (tryptophan hydroxylase, MAO A) and 5-HT(1A) receptors belong to a group of genes that modulate aggressive behaviour. PMID- 17850017 TI - [Discrimination of spectral patterns of sound signals in conditions of interfering noise]. AB - The method of probes with rippled spectra makes possible to measure the frequency resolving power (FRP) of human hearing using no frequency-selective masking techniques. This allows studying the influence of interfering noises on the FRP. In conditions of diotic presentation (parallel to both ears), FRP markedly decreases on- or low-frequency noise markedly decreases FRP. The dependence of this effect on sound intensity and noise-to-probe ratio is different for the on- and low-frequence noise, which indicates different mechanisms of action of these two kinds of interfering noise. However, in both cases, a loud enough interfering noise results in complete inability to discriminate the fine spectral pattern of the probe. On the contrary, in conditions of dichotic presentation (the probe to one ear and the noise to the other), the interfering noise does not influence FRP noticeably within a wide range of frequency relations of the probe and noise and noise-to-probe level ratios. Thus, almost entire dichotic release of influence of interfering noise on FRP takes place. This feature can be used for designing bearing aids. PMID- 17850018 TI - [Non-erythropoietic properties of erythropoietin]. AB - The review describes the capability oferythropoietin to activate and protect the CNS cells and myocardium against ischemia and hypoxia. PMID- 17850019 TI - [Stacking-interactions in the control-gear binding of kynurenic acid with NR2A- and GluR2-subunits of glutamate ionotropic receptors]. AB - Kynurenine products in tryptophan metabolism are of crucial importance in modulation of neurodegenerative processes in the CNS. Kynurenic acid (KYNA): the endogenous antagonist of ionotropic glutamate receptors, displays specific affinity towards glycine site ofNMDA-receptor NR1 subunit. Mechanisms for the selective interaction of KYNA and its derivatives with other glutamate receptor subtypes are studied insufficiently. Ab initio quantum chemical calculations for KYNA-imidazole dimer, as a model for ligand interaction with His88 fragment of NR2A-subunit, along with KYNA-phenol dimer, as a model for ligand interaction with Tyr61 fragment of GluR2-subunit, were carried out in order to investigate stacking-interaction role of KYNA binding by NR2A subunit of NMDA-receptor and GluR2 subunit of AMPA-receptor. Stacking-interaction energy of KYNA-H88 for the assumed ligand orientation in the binding site is 3.0-5.0 kcal/mol and 102. kcal/mol for the optimized dimer KYNA-imidazole geometry. Stacking-interaction energy of KYNA-Tyr61 for the assumed ligand orientation in the binding site is 6.7-8.5 kcal/mol. The obtained values are comparable with the energies of hydrogen bonds. Thus, stacking-interaction should be taken into account while studing ligand glutamate receptor binding mechanisms. Stacking-interaction is evidently important for the initial ligand orientation inside the receptor binding site after which the delicate tuning of hydrogen bonding pattern is realized. On the other hand, the specific affinity of KYNA derivatives to the receptor subunits could be explained by ligand-aromatic receptor aminoacid stacking-interaction geometry difference. PMID- 17850020 TI - [Vasopressin receptors: structure and stimulation by 1-deamino-arginine-vasotocin in rats]. AB - In experiments on non-anesthetized female Wistar rats, it has been shown that injection of 1-deamino-arginine-vasotocin (1dAVT) increases sodium excretion and solute-free water reabsorption. Antagonists of V1-receptors (OPC-31260, Otsuka Pharmaceutical Co., Ltd., Japan) eliminates the effect water reabsorption whereas antagonist of V1-receptors (OPC-21268, Otsuka Pharmaceutical Co., Ltd., Japan) decreases the 1dAVT-dependent increase of Na+ and water excretion. A model of V1 receptors an a supposed topography of their interaction with 1dAVT are constructed. PMID- 17850021 TI - [Glutamatergic regulation of citrulline extracellular level in the nucleus accumbens during acquisition and expression of conditioned emotional response]. AB - In Spregue-Dawley rats, by means of in vivo microdialysis combined with HPLC analysis, it was shown that acquisition and expression of conditioned emotional response increased extracellular level of citrulline: a nitric oxide coproduct, in the nucleus accumbens. Intraaccumbal infusion of MK-801 (100 microM): an NMDA antagonist, markedly attenuated the increase in extracellular citrulline in the n. accumbens produced by acquisition of the response, and completely prevented its conditioned rise observed during expression of the response. The data obtained suggest that, during acquisition and expression of the conditioned emotional response, glutamatergic input to the n. accumbens might act via NMDA receptors to stimulate NO production within this brain area. PMID- 17850022 TI - [Oxygen tension in cerebral microvessels in acute anaemia in rats]. AB - Using polarographic oxygen microelectrodes, distribution of oxygen tension (pO2) in the rat cerebral arterioles (with a lumen diameter of 8-80 microm) and venules (with a lumen diameter of 8-120 microm) has been studied in acute reduction of haemoglobin concentration in the blood. Isovolumic haemodilution with 5 % albumin solution has been performed stepwise from 14 g/dl (control) to 10 g/dl (step 1), 7 g/dl (step 2) and to 4.6 g/dl (step 3). It was shown that step 1 of haemodilution led to no impairment of oxygen supply to the brain cortex. Step 2 resulted in moderate increase of pO2 in arterioles, whereas in venules oxygen tension fell down substantially (on the average, to 32 mm Hg). Step 3 resulted insignificant increase of pO2 in arterioles. A further fall of pO2 (to 27 mm Hg) in studied venules was recorded. The portion of venules with low pO2 grew to 31% (only 3 % in control). Microregions with a near-to-zero pO2 were recorded in some capillaries. This indicates presence of hypoxic zones in brain tissue. Hypoxic and anoxic microregions originate at this stage of anemia in locations with relatively low and/or impaired blood supply. PMID- 17850023 TI - [The muscular blood flow in rats in ontogenesis as measured by the needle probe laser Doppler flowmeter "LAKK-01"]. AB - In anesthetized Wistar rats of the age of 4, 13, 30 and 90 days, blood flow in m. gracilis was measured with the aid of laser-Doppler flowmeter "LAKK-01" with a needle probe. The sharpest postnatal falling of a muscular blood flow was revealed in the first month of life. Features of measurement of the blood flow and biological background by a needle probe in skeletal muscles of rats of various age described. PMID- 17850024 TI - [Effects of chronic Semax administration on exploratory activity and emotional reaction in white rats]. AB - Effects of chronic intranasal administration of ACTH(4-10) analog Semax (MEHFPGP) on exploratory activity, anxiety level, and depression-like behaviour were studied in white rats. The peptide was injected daily in dose 0.05 mg/kg during 10 or 14 days. It was shown that chronic Semax administration at 1-2 weeks induced anxiolytic and antidepressant effects but did not influenced the exploratory activity in non-stressogenic environment. The Semax effects may be the results of activation of the brain serotoninergic system as well as increased BDNF expression in the rat hippocampus. PMID- 17850025 TI - [The role of lung afferent system in respiratory control during head-down tilt]. AB - The role of lung receptors in respiratory control during acute head-down tilt (AHDT, -30 degrees) was investigated in anesthetized, tracheostomized rats. The results show that AHDT increased the mechanical respiratory load, slowed inspiratory flow, reduced the end expiratory lung volume, tidal volume and minute ventilation. On the other hand, during AHDT a significant rise in inspiratory swings of oesophageal pressure was recorded indicated a compensatory increase in inspiratory muscle contraction force. These effects were reduced after transaction of the vagus nerve. It was also shown that respiratory response on added mechanical load was reduced during AHDT as compared with the value in horizontal position. This deference disappeared after vagotomy. The data obtained suggested that afferent information from lung receptors take part in compensation of respiratory effects of AHDT. The cause of reduction in respiratory response to loading during AHDT involves weakness of lung reflexes evoked by volume changes. PMID- 17850026 TI - [Europhysiom and virtual man]. PMID- 17850027 TI - How changes in the Pacific/Asia region are shaping social work education and practice in Hawai'i. PMID- 17850028 TI - Forrester Blanchard Washington and his advocacy for African Americans in the new deal. AB - Forrester Blanchard Washington (1887-1963) was an African American social work pioneer recruited to the first New Deal administration of Franklin Delano Roosevelt as director of Negro Work in the Federal Emergency Relief Administration. This role gave Washington a platform from which to object strenuously to the development of social policies that were predisposing African Americans to chronic dependence on welfare programs instead of creating equal opportunities for employment. Washington's policy analysis and recommendations represent social work's advocacy for equal employment opportunity long before the related civil rights legislation in the 1960s. An analysis is offered to explain Washington's decision to abort his federal career when the political agenda of the Roosevelt administration began to conflict with his values and professional goals. His actions are exemplary of resignation in protest--an aspect of advocacy more often discussed than used. This article is based on Washington's writings and materials found in the National Archives and Records Administration at College Park, Maryland. PMID- 17850029 TI - Situational approaches to direct practice: origin, decline, and re-emergence. AB - During the 1890s and the first three decades of the 20th century, social work in the United States developed a community-based direct practice approach to family assistance and social reform. The basis for this method was a situational view of social life that emphasized the use of interpersonal and transactional methods to achieve social and individual change. This article highlights important aspects of the genesis and development of this approach, emphasizing especially the contributions of its foremost exponents: Jane Addams, Mary Richmond, Ada Sheffield, Eduard Lindeman, and Mary Parker Follett. Also included are comments about current attempts in social work to revive this perspective for use by contemporary practitioners. PMID- 17850030 TI - Information technology acceptance in the social services sector context: an exploration. AB - Although computers and information technology (IT) have penetrated the field of social work, little research has systematically studied how users respond to this infusion. Information systems researchers have accumulated significant insights into IT acceptance in business organizations after decades of efforts. In this study, users in the social services were assessed for their acceptance of IT. A research model based on the decomposed theory of planned behavior was developed, arguing that attitudes toward using IT, subjective norms, and perceived behavioral control are important antecedents of intentions to use IT, which affect actual usage. In addition, users consider the benefits that they bring to their organizations and clients through using IT when forming their attitudes toward using IT. Data collected from users of a Homeless Management Information System in a northeastern U.S. state verified the research model. The results suggest new interventions to promote IT acceptance by users in the social services sector. PMID- 17850031 TI - Borrowing to save: a critique of recent proposals to partially privatize Social Security. AB - Concern over Social Security's forecasted long-run deficit is occurring at a time when the program has a short-term surplus. One proposed strategy to address this forecasted deficit is to allow the investment of a portion of payroll taxes into private savings accounts (PSAs). The author analyzes recent proposals for PSAs and concludes that PSAs are more likely to be a problem than a solution. Paradoxically, PSAs require the government to borrow to encourage current workers to save. The author recommends resources to help social workers remain informed about proposed program reforms and prepared to advocate for the concept of social insurance. PMID- 17850032 TI - Bending gender, ending gender: theoretical foundations for social work practice with the transgender community. AB - Gender is a ubiquitous social construct that wields power over every individual in our society. The traditional dichotomous gender paradigm is oppressive, especially for transgendered people whose sense of themselves as gendered people is incongruent with the gender they were assigned at birth. Transgendered individuals are targeted for mistreatment when others attempt to enforce conventional gender boundaries. This article discusses gender-based oppression and the resulting psychosocial difficulties experienced by many transgendered individuals. The discussion advances a critical analysis of the dominant gender paradigm using two alternative theoretical perspectives on gender--queer theory and social constructionism. The article argues that the transgender community is an at-risk population and that empowering practice with this population calls on social workers to target society's traditional gender dichotomy for change. An overview of practice implications and research needs is provided. PMID- 17850033 TI - Re-examining empathy: a relational-feminist point of view. AB - This article reviews the literature on the concept of empathy in the social work profession from the days of Mary Richmond to its use in traditional literature today. Empathy is re-examined in light of recent developments in feminist scholarship, in particular the relational-cultural theory developed at the Stone Center at Wellesley College. Moving beyond the more traditional definitions of empathy, this article presents a framework that conceptualizes empathy in an increasingly mutual, interactive, and humanist way. Case examples illustrate the need for connection and empathic responsiveness in which both worker and client feel the impact each has made on the other. Unlike earlier conceptualizations of empathy, this relational approach highlights the active participation of the worker and client system in a dynamic helping process and illustrates how the worker brings his or her own thoughts and feelings into the helping relationship. Implications for practice are discussed. PMID- 17850034 TI - Effects of service barriers on health status of older Chinese immigrants in Canada. AB - The authors examine the effects of service barriers on the health status of older Chinese immigrants in Canada. A survey was completed in seven Canadian cities by a random sample of 2,214 older Chinese immigrants age 55 years or older. Service barriers related to administrative problems, personal attitudes, and circumstantial difficulties were significant predictors of physical and mental health when controlling for the demographic factors. Empirically, the findings confirm that service barriers are detrimental to the health of older immigrants. The service barriers in the areas of ethnic, language, or cultural differences between the service providers or services themselves and the older Chinese clients also suggest that factors related to communication contribute to these older clients' perception of services or providers as culturally insensitive or unresponsive. Considering the individual, social, and economic costs incurred by adverse health consequences, barriers in service delivery must be addressed. PMID- 17850035 TI - Increasing safety for at-risk adults: screening in-home care providers. PMID- 17850036 TI - Perspective analysis: McKnight's Careless Society and the strengths-based approach to social work. PMID- 17850037 TI - In their words: secondary traumatic stress in social workers responding to the 9/11 terrorist attacks in New York City. PMID- 17850038 TI - The importance of revitalizing management education for social workers. PMID- 17850039 TI - Thoughts on health insurance expansions and the value of coverage. PMID- 17850040 TI - Public reporting and pay-for-performance: safety-net hospital executives' concerns and policy suggestions. AB - Safety-net hospitals (SNHs) may gain little financial benefit from the rapidly spreading adoption of public reporting and pay-for-performance, but may feel compelled to participate (and bear the costs of data collection) to meet public expectations of transparency and accountability. To better understand the concerns that SNH administrators have regarding public reporting and pay-for performance, we interviewed 37 executives at randomly selected California SNHs. The main concerns noted by SNH executives were that human and financial resource constraints made it difficult for SNHs to accurately measure their performance. Additionally, some executives felt that market-driven public reporting and pay for-performance may focus on clinical areas and incentive structures that may not be high-priority clinical areas for SNHs. Executives at SNHs suggested several policy responses to these concerns-such as offering training programs for SNH data collectors-that could be relatively inexpensive and might improve the cost benefit ratio of public reporting and pay-for-performance programs. PMID- 17850042 TI - Perverse incentives in the Medicare prescription drug benefit. AB - This paper analyzes some of the perverse incentives that may arise under the current Medicare prescription drug benefit design. In particular, risk adjustment for a stand-alone prescription drug benefit creates perverse incentives for prescription drug plans when making coverage decisions and/or for pharmaceutical companies when setting prices. This problem is new in that it does not arise with risk adjustment for other types of health care coverage. For this and other reasons, Medicare's drug benefit requires especially close regulatory oversight, now and in the future. We also consider a relatively minor change in financing the benefit that could lead to significant changes in how the benefit functions. In particular, if all plans were required to charge the same premium, there would be less diversity in quality, but also less need to regulate formulary composition, less budgetary uncertainty, and less upward pressure on drug prices. PMID- 17850043 TI - Nurse staffing, mortality, and length of stay in for-profit and not-for-profit hospitals. AB - The issue of differential quality in for-profit (FP) and not-for-profit (NFP) hospitals remains a critical health policy question. With research demonstrating a relationship between nurse staffing and quality, the question arises whether the relationship differs in these hospital types. Using Healthcare Cost and Utilization Project data from the period 1990-1995, we found that case mix adjusted registered nurse (RN) staffing was significantly lower in FPs than in NFPs, and we found a superior distribution of outcomes (mortality and length of stay) obtained with a lower level of RN staffing. The differences in mortality and length of stay disappeared, however, after controlling for population and market characteristics. PMID- 17850044 TI - Paying their way? Do nonprofit hospitals justify their favorable tax treatment? AB - This study addresses the effect of hospital ownership on the delivery of services to medically indigent patients and on their communities, using two alternative definitions of community benefits. Using data from hospitals in California, the study finds that in similar markets, the amount of community benefits provided by a tax-exempt private hospital is equivalent in value to that provided by an investor-owned hospital. These results are sensitive to the definition of community benefits, thus indicating need for a more explicit identification and minimum standard of the community benefits expected of nonprofit hospitals in return for their special tax treatment. PMID- 17850045 TI - Free-standing ambulatory surgery centers and hospital surgery volume. AB - This paper examines the association of free-standing ambulatory surgery centers (ASCs) with hospital surgery volume, using data from the 2002 Medicare Online Survey Certification and Reporting System and the American Hospital Association Annual Surveys of Hospitals. From 1993 to 2001, the number of ASCs per 100,000 population in metropolitan statistical areas (MSAs) increased by 150%. During the same period, hospital outpatient surgeries increased 28%, while inpatient surgeries decreased by 4.5%. MSA and year fixed-effects regression analyses suggest that an increase of one ASC per 100,000 people was associated with a 4.3% reduction in hospital outpatient surgical volume, but was not associated with inpatient surgical volume. PMID- 17850046 TI - Estimating regression standard errors with data from the Current Population Survey's public use file. AB - This study examines whether reasonable standard errors for multivariate models can be calculated using the public use file of the Current Population Survey's Annual Social and Economic Supplement (CPS ASEC). We restrict our analysis to the 2003 CPS ASEC and model three dependent variables at the individual level. income, poverty, and health insurance coverage. We compare standard error estimates performed on the CPS ASEC public use file with those obtained from the Census Bureau's restricted internal data that include all the relevant sampling information needed to compute standard errors adjusted for the complex survey sample design. Our analysis shows that the multivariate standard error estimates derived from the public use CPS ASEC following our specification perform relatively well compared to the estimates derived from the internal Census Bureau file. However, it is essential that users of CPS ASEC data do not simply choose any available method since three of the methods commonly used for adjusting for the complex sample design produce substantially different estimates. PMID- 17850047 TI - Ca, Cd, Zn, and their ions interacting with Cytosine: a theoretical study. AB - Metal atoms play a major role in the chemical behavior of biological systems. In this work, known issues of the metal-base interactions, such as the stabilization of different tautomers of cytosine that could be incompatible with the DNA double helix, are researched using DFT methods. Ca-, Zn-, and Cd-cytosine in neutral and ionic forms were studied at the B3LYP/LANL2DZ level. Several neutral and ionic isomers were found within an interval of 10 kcal/mol of relative stability, with the most stable isomer in each group being a compound derived from the canonical isomer of cytosine, except for the dications where two iso-energetic isomers were found. Interatomic lengths from each metal atom to the nearest atoms in cytosine's ring were larger than 2 A, discouraging the possibility of a covalent interaction, as supported by additional evidence from molecular orbitals. The interaction between metal and cytosine, electrostatic in nature, is reinforced with the increase of the metal's nuclear charge. Additionally, the ionization energies of the metal-cytosine compounds exhibit a significant reduction (below 6 eV) compared with that of plain cytosine (8.7 eV), posing an interesting possibility with respect to the experimental determination of the photoelectron spectra of these compounds. Analyses of the energetics of the global reactions to form cationic species show that metal cations bind more strongly to neutral cytosine than to neutral metals. Metal dications form the most stable compounds with neutral cytosine, and the stabilities of these systems decrease as (Zn cyt)2+ > (Cd-cyt)2+ > (Ca-cyt)2+. Aromaticities computed via the HOMA indexes also support the observation regarding the greater affinity of cytosine for metal cations. PMID- 17850048 TI - Carbon dioxide evolution in a Belousov-Zhabotinsky type oscillating reaction with acetonedicarboxylic acid. AB - Oscillations in the platinum redox potential during the reaction of bromate ions with acetonedicarboxylic acid catalyzed by Mn(II) ions were observed. The volume of gaseous carbon dioxide produced was measured. A nonoscillatory course was found both at the slow and rapid stirring rates for carbon dioxide evolution. The perturbation experiments suggest supersaturation during the Belousov-Zhabotinsky reaction with acetonedicarboxylic acid. Possible reasons for such observations are discussed. PMID- 17850049 TI - Thermochemistry and infrared spectroscopy of neutral and cationic iron-polycyclic aromatic hydrocarbon complexes of astrophysical interest: fundamental density functional theory studies. AB - This paper reports extensive calculations on the structural, thermodynamic, and mid-infrared spectroscopic properties of neutral and cationic model iron polycyclic aromatic hydrocarbon (PAH) complexes of astrophysical interest for three PAHs of increasing size, namely, naphthalene (C10H8), pyrene (C16H10), and coronene (C24H12). Geometry optimizations and frequency calculations were performed using hybrid Hartree-Fock/density functional theory (DFT) methods. The use of DFT methods is mandatory in terms of computational cost and efficiency to describe the electronic and vibrational structures of such large organometallic unsaturated species that present several low-energy isomers of different structures and electronic and spin states. The calculated structures for the low energy isomers of the model Fe-PAH and Fe-PAH+ complexes are presented and discussed. Iron-PAH binding energies are extracted, and the consequences of the coordination of iron on the infrared spectra of neutral and cationic PAHs are shown with systematic effects on band intensities and positions being demonstrated. The first results are discussed in terms of astrophysical implications. This work is the first step of an ongoing effort in our group to understand the photophysics and spectroscopy of iron-PAH complexes in the conditions of the interstellar medium using a synergy between observations, laboratory experiments, and theory. PMID- 17850050 TI - Kinetic approach for the study of noncovalent interaction between [Ru(NH3)5pz]2+ and gold nanoparticles. AB - Gold nanoparticles (AuNPs) capped with N-(2-mercaptopropionyl)glycine have been used to study the strength and character of the binding of a cationic metal complex, [Ru(NH3)5pz]2+ (pz = pyrazine), at pH = 8, to these nanoparticles. The strength of the binding has been studied using a kinetic approach consisting of the study of the kinetics of the oxidation of this ruthenium complex by S2O82- at different NaCl concentrations. When the ionic strength increases, the strength of the binding decreases, as a consequence of the partial neutralization of the charge on the AuNPs which, at pH = 8, has the tiopronin residue negatively charged. The increase of the ionic strength also produces a change in the character of the binding, which changes from anticooperative to noncooperative when the ionic strength increases. The nonelectrostatic and electrostatic components of the free energy of binding are determined. From the latter, we have obtained the values of the electrostatic potential differences at the AuNPs/solutions interface. PMID- 17850052 TI - Probing the influence of solvent effects on the conformational behavior of 1,3 diazacyclohexane systems. AB - The conformational behavior of a 1,3-diazacyclohexane system has been investigated using the DFT B3LYP/6-311+G** level of theory. The structural parameters and relative energies predicted that anomeric effects are operative in the conformations of 1,3-diazacyclohexane. The stability of conformers predicted in the solvent continuum model (water and acetonitrile) is similar to the gas phase results. The explicit water molecules stabilized the least-stable conformer, and the predictive trend is opposite to that of the gas-phase results. The stability of the conformers in the gas phase is a compromise between avoiding repulsions and maximizing hyperconjugative stabilization. The NBO analysis suggests that the interactions of explicit solvent molecules with 1,3 diazacyclohexane conformers attenuate the anomeric stabilization. The hydrogen bonding interactions of explicit solvent molecules with 1,3-diazacyclohexane swamped the anomeric effects to alter the conformational stability compared to the gas-phase and solvent continuum model studies. PMID- 17850051 TI - Photoinduced formation of N2 molecules in ammonium compounds. AB - Via fluorescence yield (FY) and resonant inelastic scattering spectroscopy in the soft X-ray range we find that soft X-rays induce formation of N2 molecules in solid NH4Cl and in related compounds. The nitrogen molecules form weak bonds in NH4Cl, so that a substantial fraction of the molecules remains in the sample. From measurements of the FY as a function of exposure and temperature, the rates for the photochemical processes are estimated. At elevated temperatures (363 K), several nitrogen atoms are removed from the sample per incoming photon. At lower temperatures (233 K), the rate is reduced to around 0.02 nitrogen atoms for each incoming photon. Virtually all these atoms form N2 molecules which are bound in the sample. The generality and implications of these results are briefly discussed. PMID- 17850053 TI - Theoretical and spectroscopic study of 2-substituted indan-1,3-diones: a coherent picture of the tautomeric equilibrium. AB - The structures of some 2-substituted indan-1,3-diones are investigated in the gas phase and solution using quantum chemical calculations and spectral (NMR, IR, and UV) measurements. The influence of the substituent at the 2-position on the tautomeric equilibrium of 2-substituted indan-1,3-diones in solvents with different polarity is evaluated. It is shown that the equilibrium in 2-formyl indan-1,3-dione and 2-acetyl-indan-1,3-dione is shifted to the 2 hydroxyalkylidene-indan-1,3-dione tautomer, while 2-carboxyamide-indan-1,3-dione exists as a mixture of two tautomers, 2-(hydroxyaminomethylidene)-indan-1,3-dione and 2-carboamide-1-hydroxy-3-oxo-indan, with extremely fast proton transfer between them. The situation for 2-carboxy-indan-1,3-dione is quite different - on the basis of the analysis of the obtained results, the possible existence of an anionic form of 2-carboxy-indan-1,3-dione in solution can be inferred. PMID- 17850054 TI - On the mechanism of electron-capture-induced dissociation of peptide dications from 15n-labeling and crown-ether complexation. AB - 15N-labeling of di- and tripeptides reveals that electron capture to doubly protonated peptides results almost exclusively in ammonia loss from the N terminal end, which clearly shows that a significant fraction of electron capture occurs at this end. In accordance with this finding, the competing channel of N Calpha bond breakage leads to z+* ions and neutral c fragments after electron capture to small dications. In larger peptides that live long enough for internal proton exchanges to occur, c+ ions are also formed and in some cases in dominant yield. Attachment of one or two crown ethers to ammonium groups is likely to reduce the probability of proton transfer, which enhances the formation of z+* relative to c+. The total yield of z+* and c+ is, however, more or less unchanged, which indicates that proton transfer or hydrogen transfer from a NH3 group to the amide group is not required for the N-Calpha bond breakage. PMID- 17850055 TI - Toward efficient drug screening by homogeneous assays based on the development of new fluorescent vasopressin and oxytocin receptor ligands. AB - A series of fluorescent ligands designed for vasopressin and oxytocin G protein coupled receptors was synthesized and characterized to develop fluorescence polarization or homogeneous time-resolved fluorescence (HTRF) binding assays. These ligands, labeled with europium pyridine-bis-bipyridine cryptate or with Alexa 488,546,647 selectively bound to the vasopressin V1a and oxytocin receptors with high affinities and exhibited antagonistic properties. The affinities of several unlabeled ligands determined by our homogeneous assays on membrane preparations or on intact cells into 96- and 384-well plate formats were similar to those determined by usual radioligand binding methods. Compared to other binding assays, the polarization and HTRF binding assays are nonradiaoactive, therefore safer to perform, yet very sensitive and homogeneous, therefore easier and faster to automate. These methods are thus suitable for efficient drug high throughput screening procedures and can easily be applied to other G protein coupled receptor models. PMID- 17850056 TI - Discovery of a new series of potent and selective linear tachykinin NK2 receptor antagonists. AB - Starting from 1 (MEN14268), a selective tachykinin NK2 receptor antagonist with an interesting in vitro pharmacological profile, a family of numerous antagonists was obtained through an optimization process focused on iterated structural modifications. The effects of the introduction of a wide variety of substituents on the lipophilic aromatic part of the molecule and the modulation of the structural constraint through the insertion of different achiral alpha,alpha dialkylamino acids were investigated. In particular, aromatic and benzofused heteroaromatic moieties were introduced at the pseudo-N-terminal residue to replace the 2-benzothiophene moiety, and a systematic investigation of the best positioning of substituents onto the aromatic platform was reported for the benzothiophene core. Studies on the modulation of the length and the rigidity of the hydrophilic pseudo-C-terminal pendant are presented. Many heteroaliphatic groups are well tolerated by the receptor in this part of the ligand. The product 48f (MEN15596), bearing a methyl substituent on the benzothiophene and a tetrahydropyranylmethylpiperidine pendant, was finally selected for its good in vivo activity after intravenous, intraduodenal, and oral administration in guinea pigs. PMID- 17850057 TI - Biological evaluation, structure-activity relationships, and three-dimensional quantitative structure-activity relationship studies of dihydro-beta-agarofuran sesquiterpenes as modulators of P-glycoprotein-dependent multidrug resistance. AB - Multidrug resistance (MDR) is one of the main challenges in the chemotherapy of cancer, malaria, and other important diseases. Here, we report the inhibitory activity of a series of 76 dihydro-beta-agarofuran sesquiterpenes, tested on NIH 3T3 cells expressing the human P-glycoprotein (Pgp) multidrug transporter, to establish quantitative comparisons of their respective abilities to block the drug transport activity. The screening was performed on the basis of the ability of sesquiterpenes to modulate the intracellular accumulation of the classical Pgp substrate daunorubicin. To understand the structural basis for inhibitory activity and guide the design of more potent Pgp inhibitors, we have performed a three-dimensional quantitative structure-activity relationship model using the comparative molecular similarity indices analysis (CoMSIA). The most salient features of these requirements are in the region of the substituents at the C-2, C-3, and C-8 positions, which seem to be critical for determining the overall effectiveness of sesquiterpenes as Pgp inhibitors. PMID- 17850059 TI - N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase. AB - Human neutrophil elastase (NE) plays an important role in the pathogenesis of pulmonary disease. Using high-throughput chemolibrary screening, we identified 10 N-benzoylpyrazole derivatives that were potent NE inhibitors. Nine additional NE inhibitors were identified through further screening of N-benzoylpyrazole analogues. Evaluation of inhibitory activity against a range of proteases showed high specificity for NE, although several derivatives were also potent inhibitors of chymotrypsin. Analysis of reaction kinetics and inhibitor stability revealed that N-benzoylpyrazoles were pseudoirreversible competitive inhibitors of NE. Structure-activity relationship (SAR) analysis demonstrated that modification of N-benzoylpyrazole ring substituents modulated enzyme selectivity and potency. Furthermore, molecular modeling of the binding of selected active and inactive compounds to the NE active site revealed that active compounds fit well into the catalytic site, whereas inactive derivatives contained substituents or conformations that hindered binding or accessibility to the catalytic residues. Thus, N-benzoylpyrazole derivatives represent novel structural templates that can be utilized for further development of efficacious NE inhibitors. PMID- 17850058 TI - Design, synthesis, and preliminary pharmacological evaluation of new quinoline derivatives as nicotinic ligands. AB - A series of nicotinic ligands, carrying a quinoline nucleus, and characterized by a pharmacophoric distance between the quinoline nitrogen (H-bond acceptor) and the cationic nitrogen atoms higher than that proposed in the classical pharmacophoric models, have been synthesized and tested for their affinity for the central nicotinic receptor. The enantiomers of the nicotine analogue 1-methyl 2-pyrrolidinyl-6-quinoline and of its methiodide display enantioselectivity in binding studies, but not when tested in vivo; on alpha7* nicotinic receptor enantioselectivity is inverted with respect to the alpha4beta2* subtype. N,N,N Trimethyl-4-(quinolin-6-yl)but-3-yn-1-ammonium iodide (3c) and trans-N,N,N trimethyl-4-(quinolin-6-yl)but-3-en-1-ammonium iodide (4c), showing pharmacophoric distances in the range 8.5-10.4 A, interact with the alpha4beta2* nicotinic receptor with Ki in the microM range; compound 3c shows preference for the alpha7* subtype. PMID- 17850060 TI - 4-[omega-[4-arylpiperazin-1-yl]alkoxy]phenyl)imidazo[1,2-a]pyridine derivatives: fluorescent high-affinity dopamine D3 receptor ligands as potential probes for receptor visualization. AB - Sixteen long-chain arylpiperazines bearing the fluorescent moiety 2 phenylimidazo[1,2-a]pyridine were synthesized as fluorescent dopamine D3 receptors ligands (385 nM < Ki < 0.72 nM). The most potent D3 compounds 15a and 19a (Ki = 1.6 and 0.72 nM, respectively) showed good Stokes shift and high quantum yield in ethanol (Phi = 0.74 and 0.66, respectively). In the first attempt, 15a was unable to visualize D3 receptors expressed in CHO cells by epifluorescence microscopy. PMID- 17850063 TI - Network scaling invariants help to elucidate basic topological principles of proteins. AB - The structural architecture of proteins continues to be an area of active research. Despite the difference in models dealing with the way proteins fold into their tertiary structures, it is recognized that small regions of proteins tend to fold independently and are then stabilized by interactions between these distinct subunits. However, there are a number of different definitions of what comprises an independent subunit. In the belief that an unequivocal definition of a domain must be based on the most fundamental property of protein 3D structure, namely, the adjacency matrix of inter-residues contact, we adopt a network representation of the protein. In this work, we used a well-established, global method for identifying modules in networks, without any specific reference to the kind of network being analyzed. The algorithm converges toward the maximization of the modularity of the given protein network and, in doing so, allows the representation of the residues of the protein in terms of their intramodule degree, z, and participation coefficient, P. We demonstrate that the labeling of residues in terms of these invariants allows for information-rich representations of the studied proteins as well as to sketch a new way to link sequence, structure, and the dynamical properties of proteins. We discovered a strong invariant character of protein molecules in terms of P/z characterization, pointing to a common topological design of all protein structures. This invariant representation, applied to different protein systems, enabled us to identify the possible functional role of high P/z residues during the folding process. Additionally, we observe a hierarchical behavior of protein structural organization that provides a sequence-secondary-tertiary structure link. The discovery of similar and repeatable scaling laws at different level of definitions going from hydrophobicity patterning along the sequence up to the size of an autonomous folding unit (AFU) and general contact distribution of the entire molecule suggest a hierarchical-like behavior of protein architecture. This implies the possibility to select different privileged scales of observation for deriving useful information on protein systems. PMID- 17850061 TI - Discovery and characterization of novel, potent, non-peptide parathyroid hormone 1 receptor antagonists. AB - A 1,3,4-benzotriazepine was identified as a suitable lead in our effort toward obtaining a non-peptide parathyroid hormone-1 receptor (PTH1R) antagonist. A process of optimization afforded derivatives displaying nanomolar PTH1R affinity, a representative example of which behaved as a PTH1R antagonist in cell-based cyclic adenosine monophosphate (cAMP) assays, with selectivity over PTH2 receptors. PMID- 17850064 TI - Differential recovery of peptides from sample tubes and the reproducibility of quantitative proteomic data. AB - Differential recovery of peptides due to nonspecific adsorption can seriously compromise reproducibility and quality of proteomic data for peptide analyses by liquid chromatography-mass spectrometry (LC-MS). This study demonstrates large variations in reproducibility and quantitation of LC-MS data for peptides derived from tryptic digests of BSA upon storage in different sample tubes. Notably, we show that highly improved consistency and lower errors in quantitation of BSA tryptic peptides in replicate measurements is achieved with low-retention tubes compared to regular eppendorf tubes. Furthermore, qualitative differences in peptides detected by LC-MS were observed in the two types of storage tubes. These results illustrate the necessity for careful evaluation of storage vessels and conditions to minimize variability in sample quality for LC-MS experiments. PMID- 17850065 TI - Structure, dynamics and ordering in structure i ether clathrate hydrates from single-crystal X-ray diffraction and 2H NMR spectroscopy. AB - The structure and dynamics of trimethylene oxide (TMO) and ethylene oxide (EO) structure I (sI) hydrates are reported from single-crystal X-ray diffraction and 2H NMR spectroscopic measurements. The guest molecule positions in the large cage were determined with considerable improvement over previous diffraction work so that a dynamic model that was consistent with these orientations could be developed to explain the 2H NMR data. Reorientations are shown to take place among both symmetry-related and symmetry-independent sites, 16 positions in all. Because of the prochiral nature of the molecules, both guests show 2H NMR line shapes with large asymmetry parameters, rather unusual for guest molecules in the sI hydrate large cage. The results also show that the dipolar axis of the TMO molecule lies close to the 4 bar axis of the cage on average, whereas for EO, this is not the case. For TMO, progressive alignment of the polar axis with decrease of temperature then allows the dipoles to interact more strongly until dipole reversal is quenched at the ordering transition. The lack of ordering of EO is consistent with the much weaker alignment of the molecular dipoles along the 4 bar axis. With the new complementary information on the structure and dynamics from crystallography and NMR, it is possible to understand why the large cage guests order in the large cage of sI hydrate for TMO hydrate but not for EO hydrate. PMID- 17850066 TI - Violation of distribution symmetry in statistical evaluation of absolute enantioselective synthesis. AB - Enantiomeric excesses obtained in absolute enantioselective synthesis by chiral autocatalysis (Soai-reaction) were statistically analyzed. Two sets of parallel experiments, which were performed under chemically different conditions, are available. One group contains 37, while the other contains 84 preparative results. The former group shows some interesting tendencies but does not give conclusive statistical results. The sample of 84 parallel experiments, providing 39 R- and 45 S-excesses have shown that these data represent two distinct, non symmetric sets with different non-Gaussian distributions. Clear S preference was found. PMID- 17850067 TI - Change in the acid hydrolysis mechanism of esters enforced by strongly acid microemulsions. AB - A kinetic study was carried out on the acid hydrolysis of 4-nitrophenylacetate and 4-nitrophenyllaurate in water/HOT/isooctane microemulsions. The substitution of Na+ in the sodium salt of bis(2-ethylhexyl)sulfosuccinate by H+ has permitted us to obtain a functionalized surfactant (HOT) and, consequently, strongly acid microemulsions. The use of HOT-based microemulsions allows us to reach concentrations of H+ in the aqueous core corresponding to a Hammett acidity function of H0 = -2. The rate constant at the interface and the distribution constants of the carboxylic esters throughout the different microenvironments of the microemulsion have been quantified by application of the pseudophase formalism. The results obtained show that the hydrolysis rate constant at the interface increases as the water content of the system decreases. The correlation of the rate constants at the interface of the microemulsion with the Hammett acidity function, H0 (on the basis of the Bunnett-Olsen criterion), has allowed us to confirm that the hydrolysis process takes place via an A2 mechanism for high water contents and through an A1 mechanism for values of W Se(II)) and the oxidation of phosphorus to the [R(3)P-X] cation (P(III) --> P(V)). The stepwise reduction of Se(IV) --> Se(II) --> Se(0) --> Se( II) occurs upon the successive addition of stoichiometric equivalents of Ph(3)P to SeCl(4), which can readily be monitored by 31P{(1)H} NMR spectroscopy. In the case of reacting SeX(4) with (i)Pr(2)IM, a similar two-electron reduction of the chalcogen is observed and there is the concomitant production of a haloimidazolium hexahaloselenate salt. The products have been comprehensively characterized, and the solid-state structures of [R(3)PX][SeX(3)] (9), [Ph(3)PCl](2)[TeCl(6)] (10), (i)Pr(2)IM-SeX(2) (11), and [(i)Pr(2)IM Cl](2)[SeCl(6)] (12) have been determined by X-ray diffraction analysis. These data all support two electron redox reactions and can be considered in terms of the formal reductive elimination of X2, which is sequestered by the Lewis base. PMID- 17850073 TI - Trinuclear platinum(II) 4,6-diphenyl-2,2'-bipyridyl complex with bis(diphenylphosphinomethyl)phenylphosphine auxiliary ligand: synthesis, structural characterization, and photophysics. AB - A trinuclear cyclometalated Pt(II) 4,6-diphenyl-2,2'-bipyridyl complex with bis(diphenylphosphinomethyl)phenylphosphine bridging ligand ([4-Ph(C--N- N)Pt](3)dpmp) has been synthesized and characterized. It exhibits a broad electronic absorption band from 400 to 600 nm because of its intramolecular Pt...Pt interactions that have been revealed by X-ray crystal structure analysis. This complex shows strong red emission in acetonitrile at room temperature and 77 K. The electronic and emission spectra exhibit concentration and temperature dependence. With increased concentrations, the UV band of the absorption spectrum gradually decreases and broadens, accompanied by an increase of the (1)[dsigma*,pi*] band between 400 and 600 nm. For emission spectra, the 550 nm band that originates from the mononuclear platinum(II) component gradually decreases with increased concentrations, while the band at approximately 700 nm that corresponds to the (3)[dsigma*,pi*] state increases. In addition, the UV-vis and emission spectra exhibit temperature and viscosity-dependence. The concentration-, temperature-, and viscosity-dependent characteristics indicate a conformational change of the complex arising from the rotation along the oligophosphine axis. This complex exhibits broad, positive, and strong transient difference absorption bands from the near-UV to near-IR spectral region. However, because of the increased ground-state absorption in the visible region, the nonlinear transmission of this trinuclear platinum complex decreases. PMID- 17850074 TI - Magnetic properties of synthetic libethenite Cu2PO4OH: a new spin-gap system. AB - Synthetic mineral libethenite Cu(2)PO(4)OH was prepared by the hydrothermal method, and its structure at 200 K was refined by single-crystal X-ray diffraction. The structure of Cu(2)PO(4)OH is built up from Cu2(2)O(6)(OH)2 dimers of edge-sharing Cu2O(4)(OH) trigonal bipyramids and [Cu1(2)O(6)(OH)(2)] proportional chains of edge-sharing Cu1O(4)(OH)(2) octahedra. Magnetic properties of Cu(2)PO(4)OH were investigated by magnetic susceptibility, magnetization, and specific heat measurements. Cu(2)PO(4)OH is a spin-gap system with a spin gap of about 139 K. It was shown by spin dimer analysis that, to a first approximation, the magnetic structure of Cu(2)PO(4)OH is described by an isolated square-spin cluster model defined by the Cu1-O-Cu2 superexchange J with Cu1...Cu2 = 3.429 A. The fitting analysis of the magnetic susceptibility data with a square-spin cluster model results in J/k(B) = 138 K. Specific heat data show that Cu(2)PO(4)OH does not undergo a long-range magnetic ordering down to 1.8 K. We also report vibrational properties studied with Raman spectroscopy and the thermal stability of Cu(2)PO(4)OH. PMID- 17850075 TI - Unprecedented 4(2)6(4) topological 2-D rare-earth coordination polymers from a flexible tripodal acid with additional amide groups. AB - Novel lanthanide(III) coordination polymers based on a flexible tripodal ligand with additional amide groups were obtained with interestingly unprecedented four connected 4(2)6(4) topology from the pyramidal nodes and reversible crystal-to amorphous transformation properties. PMID- 17850076 TI - Direct evidence on the existence of [Mo132]Keplerate-type species in aqueous solution. AB - We demonstrate the existence of discrete single molecular [Mo(132)] Keplerate type clusters in aqueous solution. Starting from a discrete spherical [Mo(132)] cluster, the formation of an open-basket-type [Mo(116)] defect structure is shown for the first time in solution using analytical ultracentrifugation sedimentation velocity experiments. PMID- 17850077 TI - Weak ferromagnetism in a semiconducting (ethylenedithiodiselena- dithiafulvalenoquinone-1,3-diselenolemethide)2.FeBr4 salt. AB - The 2:1 salts of a new bent donor molecule, ethylenedithiodiselenadithiafulvalenoquinone-1,3-diselenolemethide (EDT DSDTFVODS) and either an FeBr(4)- or a GaBr(4)- ion exhibit semiconducting properties and had small activation energies. The Fe(III) d spins of the FeBr(4)- salt are initially subject to a strong antiferromagnetic interaction and afterward exhibited a weak ferromagnetism at 3.8 K with a very small remanent magnetization of ca. 4 x 10(-2) mu(B) and a spin-flop near 25 kOe along the intercolumnar direction. PMID- 17850078 TI - Titanium-manganese compound with a chiral Mn3Ti center. AB - We have shown here for the first time a facile route to the molecular compound [Mn3Ti(mu3-OCH2CH2OCH3)2(mu-OCH2CH2OCH3)3(mu-Cl)Cl2(OiPr)2] with a Mn3Ti motif, where the Ti atom is in the chiral position and the Mn atoms occupy nonchiral sites. PMID- 17850079 TI - Hyperfine coupling to the bridging (17)O in the di-mu-oxo core of a Mn(III) Mn(IV) model significant to the core electronic structure of the O(2)-evolving complex in photosystem II. PMID- 17850080 TI - Insights into amine binding to biaryl phosphine palladium oxidative addition complexes and reductive elimination from biaryl phosphine arylpalladium amido complexes via density functional theory. AB - We present results on the binding of a variety amines to monoligated oxidative addition complexes of the type L1Pd(Ar)Cl, where L is 2-dicyclohexylphosphino 2',6'-dimethoxybiphenyl (SPhos, 1) or 2-dicyclohexylphosphino-2',4',6'-tri ispropylbiphenyl (XPhos, 2). The binding of an amine to oxidative addition complexes composed of 1 and 2 is more complex than with smaller ligands as intermediate Pd(II) complexes with bulky biaryl phosphine ligands disfavor amine binding to favorable conformations of oxidative addition complexes. Additionally, thermodynamic and kinetic parameters for reductive elimination from complexes of the type L1Pd(amido)Ph (where amido = EtNH, Me2N, PhNH) are discussed. From this data, we suggest a possible mechanism for (biaryl phosphine) Pd-catalyzed amination reactions that is more intricate than previously thought. PMID- 17850081 TI - Convergent preparation and photophysical characterization of dimaleimide dansyl fluorogens: elucidation of the maleimide fluorescence quenching mechanism. AB - Dimaleimide fluorogens are being developed for application to fluorescent protein labeling. In this method, fluorophores bearing two maleimide quenching groups do not fluoresce until both maleimide groups have undergone thiol addition reactions with the Cys residues of the target protein sequence [J. Am. Chem. Soc. 2005, 127, 559-566]. In this work, a new convergent synthetic route was developed that would allow any fluorophore to be attached via a linker to a dimaleimide moiety in a modular fashion. Series of dimaleimide and dansyl derivatives were thus prepared conveniently and used to elucidate the mechanism of maleimide quenching. Intersystem crossing was ruled out as a potential quenching pathway, based on the absence of a detectable triplet intermediate by laser flash photolysis. Stern Volmer rate constants were measured with exogenous dimaleimide quenchers and found to be close to the diffusion-controlled limits, consistent with electron transfer being thermodynamically favorable. The thermodynamic feasibility of the photoinduced electron transfer (PET) quenching mechanism was verified by cyclic voltammetry. The redox potentials measured for dansyl and maleimide confirm that electron transfer from the dansyl excited state to a pendant maleimide group is exergonic and is responsible for fluorescence quenching of the fluorogens studied herein. Taking this PET quenching mechanism into account, future fluorogenic protein labeling agents will be designed with spacers of variable length and rigidity to probe the structure-property PET efficiency relationship. PMID- 17850082 TI - Bisdeoxycoelenterazine derivatives for improvement of bioluminescence resonance energy transfer assays. PMID- 17850083 TI - Synthesis of tamiflu and its phosphonate congeners possessing potent anti influenza activity. PMID- 17850084 TI - Lithium hexamethyldisilazide-mediated enolizations: influence of chelating ligands and hydrocarbon cosolvents on the rates and mechanisms. AB - Enolizations of 2-methylcyclohexanone by lithium hexamethyldisilazide (LiHMDS) in the presence of three chelating ligands--trans-N,N,N',N' tetramethylcyclohexanediamine, N,N,N',N'-tetramethylethylenediamine, and dimethoxyethane--reveal an approximate 40-fold range of rates. NMR spectroscopic analyses and rate studies reveal isostructural transition structures based on monomeric LiHMDS for the diamines. Rate studies of LiHMDS/dimethoxyethane mediated enolizations implicate a substantial number of monomer- and dimer-based mechanisms. The rate laws vary for the three ligands because of ligand-dependent structural differences in both the reactants and the transition structures. The importance of LiHMDS-ketone complexes and the role of hydrocarbon cosolvents are discussed. PMID- 17850085 TI - Label-free electrochemical detection of DNA in blood serum via target-induced resolution of an electrode-bound DNA pseudoknot. PMID- 17850086 TI - Total synthesis of (+)-sarain A. AB - This article describes the details of our synthetic studies toward the complex marine alkaloid sarain A. Various strategies were conceived, setbacks encountered, and solutions developed, ultimately leading to a successful enantioselective total synthesis. Our route to (+)-sarain A features a number of key steps, including an asymmetric Michael addition to install the C4'-C3'-C7' stereotriad, an enoxysilane-N-sulfonyliminium ion cyclization to set the C3 quaternary carbon stereocenter, and assemble the diazatricycloundecane core, a ring-closing metathesis to construct the 13-membered ring, an intramolecular Stille coupling to fashion the unsaturated 14-membered macrocycle, and a late stage installation of the tertiary amine-aldehyde proximity interaction. PMID- 17850088 TI - Synthesis and properties of 2,3,6,7-tetraarylbenzo[1,2-b:4,5-b']difurans as hole transporting material. PMID- 17850087 TI - Photoswitchable molecular glue for DNA. PMID- 17850089 TI - Effect of soybean phospholipids on canthaxanthin lipoproteins transport, digestibility, and deposition in rainbow trout (Oncorhynchus mykiss) muscle. AB - This study was designed to assess the effect of dietary soybean phospholipids on canthaxanthin transport by serum lipoproteins and canthaxanthin muscle deposition in trout. Three groups of 12 immature trout in triplicate with a mean body weight of 130 g were fed with three experimental diets containing (1) canthaxanthin plus lecithin plus fish oil, (2) canthaxanthin plus lecithin, and (3) canthaxanthin alone, for 12 days. The two major lipoprotein classes in rainbow trout are high density lipoproteins, which transport principally carotenoids present in the serum, and low-density lipoproteins, which are responsible for the transport of cholesterol, both independently of the administered diet. In addition, very low density lipoproteins are responsible for triglyceride transport in serum. Nevertheless, the amount of canthaxanthin in the serum increased when carotenoid was associated with phospholipids plus fish oil. When canthaxanthin is transported by lecithin plus fish oil, the amount of phospholipids, cantaxanthin, and cholesterol deposited in muscle increased but not significantly. The highest apparent canthaxanthin digestibility coefficient was obtained when canthaxanthin was carried by lecithin plus fish oil. The administration of canthaxanthin carried by phospholipids improved its accumulation in the muscle of rainbow trout. This accumulation could be enhanced if the time of administration of canthaxanthin is increased. PMID- 17850090 TI - Interactions between flavan-3-ols and poly(L-proline) studied by isothermal titration calorimetry: effect of the tannin structure. AB - Interactions of proline-rich proteins (PRPs) with flavan-3-ols was studied using poly(L-proline) as a model protein by means of isothermal titration calorimetry (ITC). Several parameters were varied: (i) the galloylation and B-ring trihydroxylation of the flavan-3-ols (catechin, epicatechin, epicatechin gallate, and epigallocatechin gallate) and (ii) the degree of polymerization (monomers were compared to a mixture of oligomers with average degree of polymerization of 3.85). Large differences were observed between the flavan-3-ol monomers: no enthalpy change was measured when catechin and epicatechin were titrated by poly(L-proline), whereas thermodynamic parameters were determined in the case of galloylated monomers and mixture of oligomers. Stoichiometry ranged from 1 oligomer bound for each 12 proline units to 1 galloylated monomer for each 8 or 10 proline units. Association constants were in the range of 10(4)-10(5) M(-1), indicating a relatively high affinity of galloylated flavanols toward poly(L proline), and the coexistence of both enthalpy- and entropy-driven phenomena was suggested. Finally, the binding of grape seed tannins to proteins was shown to be a cooperative process. PMID- 17850091 TI - First total synthesis of vialinin A, a novel and extremely potent inhibitor of TNF-alpha production. AB - Vialinin A, a powerful inhibitor (IC50 90 pM) of TNF-alpha production, was synthesized from sesamol in 11 steps with 28% overall yield. The key reactions include a double Suzuki coupling of electron-rich aryl triflate with phenylboronic acid and an oxidative deprotection of bis-MOM ether. In addition, the related synthetic studies also suggest the necessity for structural revision of ganbajunin C, a positional isomer of vialinin A. PMID- 17850092 TI - Stereoselective syntheses of 4-oxa diaminopimelic acid and its protected derivatives via aziridine ring opening. AB - Regio- and stereoselective aziridine ring opening with oxygen nucleophiles derived from serine and threonine provides a route to stereochemically pure 4-oxa 2,6-diaminopimelic acid (oxa-DAP) and its methyl-substituted derivatives. Oxa-DAP is a substrate of DAP epimerase, a key enzyme for biosynthesis of l-lysine and formation of peptidoglycan precursors. Orthogonally protected analogues of lanthionine and beta-methyllanthionine wherein oxygen replaces sulfur were prepared that could be used for solid-supported peptide synthesis to make oxa derivatives of lantibiotics. PMID- 17850093 TI - A one-step fusion of 1,3-thiazine and pyrimidine cycles. AB - The chlorotrimethylsilane-promoted Biginelli type reactions of aldehydes, thiourea, and cyanoketones led to a diverse set of tetrahydropyrimidine-2(1H) thiones. Under similar conditions, thioureas, benzaldehyde, and cyanoacetamide reacted to give first representatives of hexahydro-5H-pyrimido[5,4-e][1,3]thiazin 5-ones in high preparative yield. PMID- 17850095 TI - The Wurtz-Fittig reaction in the preparation of C-silylated calixarenes. AB - The Wurtz-Fittig reaction of tetraiodo calixarene 3 with Na/Me3SiCl in DME gave a mixture of tetrakis- and tris-silylated calixarenes (6 and 7). Tris(silyl) calixarene 7 was assigned the flattened cone conformation. A model study using p bromoanisole and p-iodoanisole with Na/Me3SiCl gave the best results with p bromoanisole in toluene. Attempts to extend this reaction to the tetrabromo calixarene 4 resulted in slow reactions giving mixtures of products. However, the Wurtz-Fittig reaction of the bromo benzyloxycalixarene 5 was faster, giving the debenzylated silyl ether 12. PMID- 17850094 TI - Quinine synthesis studies: a radical-ionic annulation via Mn-mediated addition to chiral N-acylhydrazones. AB - A radical-ionic annulation approach to functionalized perhydroisoquinolines involving Mn-mediated coupling of alkyl iodides and chiral N-acylhydrazones was achieved using only 1.25 equiv of the alkyl iodide. Application of this reaction to alkene-containing substrates en route to quinine offered modest yields, decreasing on scaleup. Control experiments revealed that the alkene interfered with the coupling reaction. A revised approach involving prior oxidation of the alkene offered 93% yield in the Mn-mediated coupling, with the adduct obtained as a single diastereomer. PMID- 17850096 TI - Calix[4]arenes with siloxanes bridging opposite rings. AB - Several C-silylated (allyldimethylsilyl) calixarenes (1, 14, and 18) were treated with commercial TBAF in THF, giving the novel calixarenes 2, 15, and 19, in which the opposite rings were bridged by a Si-O-Si siloxane group. Compound 19 and the derived phenol 20 (as well as the dibromocalixarene precursor 17) were mixtures of cone and partial cone conformations according to NMR, while 2 and 15 (as well as 14 and the cone components of 17, 19, and 20) were in flattened cone conformations. PMID- 17850097 TI - Sequential Cu-catalyzed amidation-base-mediated camps cyclization: a two-step synthesis of 2-Aryl-4-quinolones from o-halophenones. AB - A direct two-step method for the preparation of 2-aryl- and 2-vinyl-4-quinolones that utilizes a copper-catalyzed amidation of o-halophenones followed by a base promoted Camps cyclization of the resulting N-(2-ketoaryl)amides is described. With CuI, a diamine ligand, and base as the catalyst system, the amidation reactions proceed in good yields for a range of aryl, heteroaryl, and vinyl amides. The subsequent Camps cyclization efficiently provides the desired 4 quinolones with the conditions that are described. PMID- 17850098 TI - Facial selectivity in the nucleophilic additions of vinylmagnesium bromide to bicyclo[2.2.2]oct-5-en-2-one derivatives. AB - The levels of diastereoselection attainable by addition of vinylmagnesium bromide to a selection of bicyclo[2.2.2]octenone derivatives 1-6 in the presence of various Lewis acids such as LiBr, CeCl3, TiCl4, ZnBr2, MgBr2, and Et2AlCl have been determined. The 1,2-addition of ketone 1 with vinylmagnesium bromide in THF provided a mixture of anti- and syn-isomers. The reactions of 2 with vinylmagnesium bromide at room temperature afforded anti- and syn-isomers with preference to anti-isomers in most cases. These reactions in the presence of Lewis acids afforded anti-isomers as the major product with an excellent stereoselectivity or as single isomers in some cases. The ketones 3 gave surprisingly different results providing anti-isomers predominantly even in the presence of Lewis acids. The bicyclic ketones 4 and 5 and all-carbon tricyclic ketone 6 furnished the syn-isomer as the main product. There is no significant effect of Lewis acid catalysis in the nucleophilic addition reactions of 1, 4, 5, and 6. The use of a preformed vinylmagnesium bromide-CeCl3 reagent for the addition reactions of 2d-f and 3d-f provided almost exclusively syn-isomers. The substituents and reaction conditions can influence facial selectivity in the nucleophilic additions to the bicyclo[2.2.2]oct-5-en-2-one derivatives. PMID- 17850099 TI - A comparative study of amphiphilic PAMAM dendrimers at the air-water interface with different hydrophobe attachment groups. AB - Generation 0 through 5 polyamidoamine (PAMAM) dendrimers with three different types of groups connecting to hydrophobic C12 tails and one type of group connecting to C18 tails were synthesized and studied as monolayers at the air water interface with a Langmuir trough. The molecular areas were significantly influenced by the size and the type of connecting group. Higher-generation (e.g., G4 and G5) amphiphilic PAMAMs with amide connecting groups were more responsive to changes in compression rate and subphase temperature and less stable than the corresponding opened epoxide- or ester-connected counterparts. Intramolecular (and possibly also intermolecular) attractive hydrogen-bond interactions between the amide connectors are proposed as the reason for this behavior. PMID- 17850100 TI - Electrochemically deposited palladium as a substrate for self-assembled monolayers. AB - The vast majority of reports of self-assembled monolayers (SAMs) on metals focus on the use of gold. However, other metals, such as palladium, platinum, and silver offer advantages over gold as a substrate. In this work, palladium is electrochemically deposited from PdCl2 solutions on glassy carbon electrodes to form a substrate for alkanethiol SAMs. The conditions for deposition are optimized with respect to the electrolyte, pH, and electrochemical parameters. The palladium surfaces have been characterized by scanning electron microscopy (SEM) and the surface roughness has been estimated by chronocoulometry. SAMs of alkane thiols have been formed on the palladium surfaces, and their ability to suppress a Faradaic process is used as an indication for palladium coverage on the glassy carbon. The morphology of the Pd deposit as characterized by SEM and the blocking behavior of the SAM formed on deposited Pd delivers a consistent picture of the Pd surface. It has been clearly demonstrated that, via selection of experimental conditions for the electrochemical deposition, the morphology of the palladium surface and its ability to support SAMs can be controlled. The work will be applied to create a mixed monolayer of metals, which can subsequently be used to create a mixed SAM of a biocomponent and an alkanethiol for biosensing applications. PMID- 17850101 TI - Intercalation of poly(oxyethylene) alkyl ether into a layered silicate kanemite. AB - Poly(oxyethylene) alkyl ether (CnEOm) is intercalated into the interlayer space of a layered silicate kanemite by using layered hexadecyltrimethylammonium (C16TMA) intercalated kanemite (C16TMA-kanemite) as the intermediate. C16TMA kanemite was treated with an aqueous solution of C16EO10, and the intercalation of C16EO10 was confirmed by the slight increase in the basal spacing (from 2.92 to 3.34 nm) with the increase in the carbon content, yielding C16EO10-C16TMA kanemite. The product was dispersed again in a C16EO10 aqueous solution, and then 1.0 M HCl was added to the suspension to remove C16TMA ions completely. The basal spacing was further increased (from 3.34 to 5.52 nm) and the content of nitrogen was virtually zero, indicating further intercalation of C16EO10 molecules and complete elimination of C16TMA ions simultaneously. Though C16EO10 molecules are not directly intercalated into kanemite, the mutual interactions among C16TMA ions, C16EO10 molecules, and the interlayer silicate surfaces effectively induce the intercalation of C16EO10. C16EO10-kanemite shows a reversible adsorption of n decane and water owing to the hydrophobicity and hydrophilicity of C16EO10, respectively, in the interlayer space. Layered CnEO10-kanemites (n = 12 and 18) were also synthesized in a manner similar to layered C16EO10-kanemite. PMID- 17850102 TI - Oriented nucleation of hydroxylapatite crystals on spider dragline silks. AB - Spider dragline silk as a protein fiber can be pictured as the oriented organization of protein nanocrystals along the long axis with their spacing filled by amorphous protein domains. We used the surface of the spider dragline silk as a biological template to nucleate bone mineral hydroxylapatite (HAP) site specifically from a HAP-supersaturated solution. HAP crystals were found to be nucleated on the surface of silks with their c axis preferentially oriented at an average angle of 72.9 degrees with respect to the long axis of the silks. The preferred orientation is nearly identical among the different mineralized silks that we studied. Other materials such as Au and CdS could be nucleated on the silks but did not show any preferred orientation. We believe that the oriented nucleation of HAP is directly related to the structures of silks and HAP. The mineralized silks will combine the good mechanical properties of the spider silks and the biocompatibility of HAP and may be assembled into ideal biomaterials as bone implants. PMID- 17850103 TI - Incomplete lipid chain freezing of sonicated vesicular dispersions of double tailed ionic surfactants. AB - Lipid freezing in dilute sonicated vesicular dispersions was studied using differential scanning calorimetry (DSC) and 1H NMR. For charged, anionic, or cationic lipids, approximately half of the lipids remain in a fluid state when cooled 20 degrees C below the main chain melting temperature. With a zwitterionic phospholipid, on the other hand, essentially no supercooling of the liquid state was observed. The observations are analyzed in terms of the nucleation and growth of flat solid domains in originally fluid spherical vesicles. As the solid domains grow, the remaining fluid domain is deformed, resulting in a curvature stress. Depending on the vesicle size and the bilayer bending rigidity, the solid domain growth may terminate as the gain in cohesive free energy is balanced by the curvature stress of the remaining fluid domain. It is argued that high bending rigidities are required for having a significant supercooling, which is why it is only observed for charged lipids. PMID- 17850104 TI - Anomalous behavior of amine oxide surfactants at the air/water interface. AB - A commonly stated requirement for the preparation of stable Langmuir monolayers of amphiphilic molecules at an air/water interface is that the surfactant must be insoluble in the subphase solution; however, a few prior studies have reported that some soluble surfactants can, under certain conditions, be compressed. The anomalous compression of soluble amphiphiles is extremely interesting and important, as it presents the possibility of greatly increasing the number of candidate compounds suitable for Langmuir monolayer studies and Langmuir-Blodgett deposition. The aim of this work was to obtain a better understanding of the factors that determine whether monolayers of a given water-soluble surfactant can be compressed. A series of amine oxide surfactants, including a novel gemini surfactant, were studied to explore the relationship between molecular structure and behavior at the air/water interface. Amine oxides are an especially interesting class of surfactants because their self-assembly in solution and at interfaces is pH-sensitive. Surface pressure-area isotherms show that the solubility of a surfactant in the subphase solution is not, in and of itself, a useful parameter in predicting whether the monolayer is compressible. Molecular modeling calculations suggest that the tendency of molecules to self-assemble plays a much more important role than solubility in this regard. The effect of pH was also investigated. We present a hypothesis that formation of dimers or small clusters of molecules at the interface inhibits the dissolution of these species into the subphase, and as a consequence the monolayer can be compressed. PMID- 17850105 TI - Solubilization of amphiphilic carboxylic acids in nonionic micelles: determination of partition coefficients from pKa measurements and NMR experiments. AB - The solubilization of octylamidotartaric acid (C8T) and octanoic acid (C8C) in Triton X-100 and Brij 58 nonionic micelles has been studied by pHmetric and 1H NMR self-diffusion experiments. As both C8C and C8T exhibit acid-base properties, a distinction between the partition of the neutral acidic form, in terms of the partition coefficient KPH, and the partition of the charged basic form, in terms of the partition coefficient KP-, has been made. The acidity constants, Ka, of C8T and C8C in the presence of micelles have been evaluated from pHmetric experiments. For both solutes, an increase in the pKa is observed in micellar media due to the difference in the partition of acidic and basic forms of the solutes. A model has been developed to determine KPH and KP- from the pKa shifts observed. The values obtained by this pKa shift modeling method and those from self-diffusion coefficient measurements are in good agreement. The acidic form of C8C is incorporated to a larger extent into the Brij 58 micelles than the acidic form of C8T, whereas the opposite trend is observed for the basic forms. Both the acidic and basic forms of C8T are more easily incorporated into Brij 58 micelles than into Triton X-100 micelles. The influence of the structure of the polar head on the solubilization properties is demonstrated. Moreover, evidence for the localization of the solutes in the micelles is obtained from the comparison of the partition coefficients and from 1H NMR data. PMID- 17850106 TI - Constituents of Ocimum sanctum with antistress activity. AB - Three new compounds, ocimumosides A (1) and B (2) and ocimarin (3), were isolated from an extract of the leaves of holy basil (Ocimum sanctum), together with eight known substances, apigenin, apigenin-7-O-beta-D-glucopyranoside, apigenin-7-O beta-D-glucuronic acid ( 4), apigenin-7- O-beta- d-glucuronic acid 6''-methyl ester, luteolin-7-O-beta-D-glucuronic acid 6''-methyl ester, luteolin-7-O-beta-D glucopyranoside, luteolin-5-O-beta-D-glucopyranoside, and 4-allyl-1-O-beta-D glucopyronosyl-2-hydroxybenzene (5), and two known cerebrosides. The structures of the new compounds were determined on the basis of extensive 1D and 2D NMR spectroscopic analysis. The new compounds (1- 3) and the known compounds 4 and 5 were screened at a dose of 40 mg/kg body weight for acute stress-induced biochemical changes in male Sprague-Dawley rats. Compound 1 displayed promising antistress effects by normalizing hyperglycemia, plasma corticosterone, plasma creatine kinase, and adrenal hypertrophy. Compounds 2 and 5 were also effective in normalizing most of these stress parameters. In contrast, compounds 3 and 4 were ineffective in normalizing any of these effects. PMID- 17850107 TI - Natural products in parallel chemistry--novel 5-lipoxygenase inhibitors from BIOS based libraries starting from alpha-santonin. AB - Recently, we developed a concept known as biology-oriented synthesis (BIOS), which targets the design and synthesis of small- to medium-sized compound libraries on the basis of genuine natural product templates to provide screening compounds with high biological relevance. We herein describe the parallel solution phase synthesis of two BIOS-based libraries starting from alpha-santonin (1). Modification of the sesquiterpene lactone 1 by introduction of a thiazole moiety followed by a Lewis-acid-mediated lactone opening yielded a first library of natural product analogues. An acid-mediated dienone-phenol rearrangement of 1 and a subsequent etherification/amidation sequence led to a second natural product-based library. After application of a fingerprint-based virtual screening on these compounds, the biological screening of 23 selected library members against 5-lipoxygenase resulted in the discovery of four potent novel inhibitors of this enzyme. PMID- 17850108 TI - Dexamethasone-conjugated low molecular weight polyethylenimine as a nucleus targeting lipopolymer gene carrier. AB - Dexamethasone, a glucocorticoid steroid, can dilate the nuclear pore complexes and translocate into the nucleus when it is bound to its glucocorticoid receptor, suggesting that the transport of DNA into the nucleus may be facilitated by the reagent. In this research, dexamethasone was conjugated to low molecular weight polyethylenimine (2 kDa) for efficient translocation of the polymer/DNA complex into the nucleus. Polyethylenimine (PEI)-dexamethasone (PEI-Dexa) was synthesized by one-step reaction using the Traut's reagent. In gel retardation assay, the PEI Dexa/DNA complex was completely retarded at or above 0.3/1 weight ratio (polymer/DNA). The average size distributions and zeta-potential values of the complexes were measured at various weight ratios. In vitro transfection assay showed that the PEI-Dexa/DNA complex had higher gene delivery efficiency compared to PEI 2kDa/DNA complex. The localization of PEI-Dexa/plasmid DNA complexes in the nucleus was confirmed by using total internal reflection fluorescence and Nomarski differential interference contrast microscope as well as confocal microscope. Therefore, with efficient nuclear translocation and low cytotoxicity, PEI-Dexa may be useful for nonviral gene therapy. PMID- 17850109 TI - Site-specific delivery of oligonucleotides to hepatocytes after systemic administration. AB - We previously complexed ODN with galactosylated poly( l-lysine) (Gal-PLL) to enhance its site-specific delivery to hepatocytes. To avoid the use of polycations, in this study we conjugated galactosylated poly(ethylene glycol) (Gal-PEG (MW of PEG: 3486 +/- 500 Da)) to ODN via an acid-labile ester linkage of beta-thiopropionate. Following tail vein injection into rats, Gal-PEG- 33P-ODN rapidly cleared from the circulation and 60.2% of the injected dose accumulated in the liver at 30 min postinjection, which was significantly higher than that deposited after injection of 33P-ODNs. The plasma concentration versus time profile of Gal-PEG- 33P-ODN was biphasic, with 4.38 +/- 0.36 min as t1/2 of distribution and 118.61 +/- 22.06 min as t1/2 of elimination. Prior administration of excess Gal-BSA decreased the hepatic uptake of Gal-PEG- 33P-ODN from 60.2% to 35.9%, suggesting galactose triggers the asialoglycoprotein receptor-mediated endocytosis of Gal-PEG- 33P-ODN by hepatocytes. A large proportion of the injected Gal-PEG- 33P-ODN was taken up by the hepatocytes as evidenced by determination of radioactivity in the digested liver cells upon liver perfusion and separation by centrifugation on a Nycodenz gradient. In conclusion, Gal-PEG-ODN conjugate may be used for treating a variety of liver diseases. PMID- 17850110 TI - Ionization and solubility of chitosan solutions related to thermosensitive chitosan/glycerol-phosphate systems. AB - Chitosan is a linear cationic biopolymer composed of glucosamine and N-acetyl glucosamine that is only soluble in acidic aqueous solutions and precipitates when neutralized. However, it was recently discovered that chitosan dissolved in solutions containing glycerol phosphate was soluble at near neutral pH and produced a sol-gel transition when heated. Understanding this unique thermogelling system requires improved characterization of the ionization and solubility behaviors of chitosan, in particular dependencies on temperature, salt, chitosan concentration, and fD, where fD is the fraction of glucosamine monomers (deacetylated monomers) in chitosan. In the current study we performed temperature-controlled titration and dilution experiments on chitosan solutions with fD of 0.72, 0.85, and 0.98 at concentrations ranging from 1.875 to 30 mM of its glucosamine monomer and with 0 to 150 mM added salt. Light transmittance measurements were performed during titration to indicate precipitation. We found the apparent proton dissociation constant of chitosan, pKap, to (1) decrease strongly with increased temperature, (2) increase strongly with increased salt, (3) increase strongly with increased chitosan concentration in low-salt conditions, and (4) decrease weakly with increasing fD. All of the above influences on chitosan pKap were accurately predicted using a mean-field Poisson Boltzmann (PB) cylindrical cell model where the only adjustable parameter was the temperature-dependent chitosan intrinsic monomeric dissociation constant pK0(T). The resulting chitosan pK0 values at 25 degrees C were in the range from 6.63 to 6.78 for all chitosans and salt contents tested. The temperature dependence of chitosan ionization was found to strongly reduce pK0(T) by 0.023 units per degrees C, for example, resulting in a reduction of chitosan pK0(T) from 7.1 at 5 degrees C to 6.35 at 37 degrees C for fD of 0.72 in 150 mM salt. A similar temperature-dependent reduction of the pKa of the glucosamine monomer was found ( 0.027 units per degrees C) while the pKa of glycerol phosphate did not change significantly with temperature. The latter result suggested that chitosan solutions heated in the presence of glycerol phosphate will become partly neutralized by transferring protons to glycerol phosphate and thereby allow attractive interchain forces to form a physically cross-linked gel under the appropriate conditions. Additionally, the degree of ionization of chitosan when it precipitates upon addition of a strong base was measured to be in the range from 0.25 to 0.55 and was found to (1) be insensitive to temperature, (2) increase strongly with increased salt, and (3) increase strongly with fD. The salt effect was accounted for by the PB model, while the influence of fD appeared to be due to acetyl groups impeding attractive chain-to-chain association to increase solubility and require reduced ionization levels to precipitate. PMID- 17850111 TI - Construction of viscoelastic biocompatible films via the layer-by-layer assembly of hyaluronan and phosphorylcholine-modified chitosan. AB - Films of hyaluronan (HA) and a phosphorylcholine-modified chitosan (PC-CH) were constructed by the polyelectrolyte multilayer (PEM) deposition technique and their buildup in 0.15 M NaCl was followed by atomic force microscopy, surface plasmon resonance spectroscopy (SPR), and dissipative quartz crystal microbalance (QCM). The HA/PC-CH films were stable over a wide pH range (3.0-12.0), exhibiting a stronger resistance against alkaline conditions as compared to HA/CH films. The loss and storage moduli, G' and G", of the films throughout the growth of eight bilayer assemblies were derived from an impedance analysis of the QCM data recorded in situ. Both G' and G" values were one order of magnitude lower than the moduli of HA/CH films. The fluid gel-like characteristics of HA/PC-CH multilayers were attributed to their high water content (50 wt %), which was estimated by comparing the surface coverage values derived from SPR and QCM measurements. Given the versatility of the PEM methodology, HA/PC-CH films are attractive tools for developing biocompatible surface coatings of controlled mechanical properties. PMID- 17850112 TI - A poly(cyclopentadithiophene) matrix suitable for electrochemically controlled DNA delivery. AB - A conducting polymer is tested for DNA delivery trials. The conducting matrix used is successful for electrochemical delivery of DNA accumulated by covalent immobilization. The electrochemical process consists of the reduction of arylsulfonamide moieties, which occur as linker groups. The specific design of the polymer allows the electronic properties to be promoted, making available the cleavage potential in physiological media. The amount of DNA released from a modified platinum electrode is investigated by quartz crystal microbalance. The released species used to prove the system performance are long sequences of DNA strands, which are amplified by PCR after liberation and identified by electrophoresis migration. PMID- 17850113 TI - Ion funnel trap interface for orthogonal time-of-flight mass spectrometry. AB - A combined electrodynamic ion funnel and ion trap coupled to an orthogonal acceleration (oa)-time-of-flight mass spectrometer was developed and characterized. The ion trap was incorporated through the use of added terminal electrodynamic ion funnel electrodes enabling control over the axial dc gradient in the trap section. The ion trap operates efficiently at a pressure of approximately 1 Torr, and measurements indicate a maximum charge capacity of approximately 3 x 10(7) charges. An order of magnitude increase in sensitivity was observed in the analysis of low concentration peptides mixtures with orthogonal acceleration (oa)-time-of-flight mass spectrometry (oa-TOF MS) in the trapping mode as compared to the continuous regime. A signal increase in the trapping mode was accompanied by reduction in the chemical background, due to more efficient desolvation of, for example, solvent related clusters. Controlling the ion trap ejection time was found to result in efficient removal of singly charged species and improving signal-to-noise ratio (S/N) for the multiply charged analytes. PMID- 17850114 TI - Carbohydrate recognition by a large sialidase toxin from Clostridium perfringens. AB - Myonecrotic isolates of Clostridium perfringens secrete multimodular sialidases, often termed "large sialidases", that contribute to the virulence of this bacterium. NanJ is the largest of the two secreted sialidases at 1173 amino acids and comprises 6 different modules which are, from the N-terminus, a family 32 carbohydrate binding module (CBM), a family 40 CBM, a family 33 glycoside hydrolase, a module of unknown function, a family 82 "X-module" of unknown function, and a module with amino acid similarity to fibronectin type III domains. The hydrolase activity of clostridial sialidases is quite well documented; however, the functions of their accessory domains are entirely uninvestigated. Here we describe the carbohydrate binding activity of the isolated family 32 CBM (CBM32) and the isolated family 40 CBM (CBM40). CBM32 is shown to bind galactose or N-acetylgalactosamine, while CBM40 is sialic acid specific, though both CBMs appear to bind with very low affinities. The crystal structure of CBM32 was determined at 2.25 A in complex with galactose. This revealed what appears to be a very simple galactose binding site. The crystal structure of CBM40 was determined at 2.20 A in complex with a sialic acid containing molecule that it fortuitously crystallized with, revealing the molecular details of the CBM40-sialic acid interaction. Overall, the results indicate that NanJ contains carbohydrate specific binding modules that likely function to target the enzyme to molecules or cells bearing mixed populations of glycans that terminate in either galactose/N-acetylgalactosamine or sialic acid. PMID- 17850115 TI - Scientific aspects of polymer electrolyte fuel cell durability and degradation. PMID- 17850116 TI - Photoinduced vibrational coherence transfer in molecular dimers. AB - At short times that are faster than dephasing, photoinduced evolution of the vibrational subsystem in an electron-phonon molecular structure depends strongly on the electronic evolution. As the electronic population shifts between the donor and acceptor states, in the diabatic description the state with the largest population determines the equilibrium positions and frequencies of the vibrational modes, which oscillate continuously and without loss of coherence. The vibrational coherence transfer between the electronic states detected recently in a number of systems is described theoretically by application of the quantized Hamiltonian dynamics (QHD) formalism [J. Chem. Phys. 2000, 113, 6557] to the coupled electronic and vibrational degrees of freedom of a model heterodimer. The observed coherent modulation of the frequency of the probe signal is represented with simple analytic and numeric QHD models. PMID- 17850117 TI - Structure and infrared spectroscopy of group 6 transition-metal carbonyls in the gas phase: DFT studies on M(CO)n (M = Cr, Mo, and W; n = 6, 5, 4, and 3). AB - B3LYP-based density functional theory (DFT) calculations with effective core potentials (ECPs) (LANL2DZ) on M and 6-311+G(2d) all-electron basis function sets on C and O are used to interpret the symmetry characteristic vibrational absorption patterns of CO ligands in the "naked" coordinatively unsaturated transition-metal carbonyls M(CO)n-1 (M = Cr, Mo, and W; n = 4-6) observed by a time-resolved infrared absorption spectroscopy after the UV pulse laser photolysis of M(CO)6 in the gas phase. The UV photolysis results can be reasonably explained by the trends in the calculated bond dissociation enthalpies of M(CO)n-1-CO for group 6 metal carbonyls. M(CO)n-1 produced through one CO elimination from M(CO)n is found out to keep its parent skeleton, resulting in the structure with symmetry of C4v for M(CO)5, C2v for M(CO)4, and C3v for M(CO)3. PMID- 17850118 TI - Kinetic study of heterogeneous reaction of deliquesced NaCl particles with gaseous HNO3 using particle-on-substrate stagnation flow reactor approach. AB - Heterogeneous reaction kinetics of gaseous nitric acid with deliquesced sodium chloride particles NaCl(aq) + HNO3(g) --> NaNO3(aq) + HCl(g) were investigated with a novel particle-on-substrate stagnation flow reactor (PS-SFR) approach under conditions, including particle size, relative humidity, and reaction time, directly relevant to the atmospheric chemistry of sea salt particles. Particles deposited onto an electron microscopy grid substrate were exposed to the reacting gas at atmospheric pressure and room temperature by impingement via a stagnation flow inside the reactor. The reactor design and choice of flow parameters were guided by computational fluid dynamics to ensure uniformity of the diffusion flux to all particles undergoing reaction. The reaction kinetics was followed by observing chloride depletion in the particles by computer-controlled scanning electron microscopy with energy-dispersive X-ray analysis (CCSEM/EDX). The validity of the current approach was examined first by conducting experiments with median dry particle diameter D(p) = 0.82 microm, 80% relative humidity, particle loading densities 4 x 10(4) 4)-d-glucan with 14 glucose units are also presented, demonstrating that the MS-CG algorithm is also applicable to the coarse-graining of other saccharide systems. PMID- 17850134 TI - Planar or nonplanar: what is the structure of urea in aqueous solution? AB - A combined quantum chemical statistical mechanical method has been used to study the solvation of urea in water, with emphasis on the structure of urea. The model system consists of three parts: a Hartree-Fock quantum chemical core, 99 water molecules described with a polarizable force-field, and a dielectric continuum. A free-energy profile along the transition of urea from planar to a nonplanar structure is calculated. This mode in aqueous solution is found to be floppy. That is, the structure of urea in water is not well-defined because the planar to nonplanar transition requires an energy of the order of the thermal energy at room temperature. We discuss the implications of this finding for simulation studies of urea in polar environments like water and proteins. PMID- 17850135 TI - Local structure refinement of disordered material models: ion pairing and structure in YCl3 aqueous solutions. AB - Hydrogen/deuterium isotopic neutron diffraction techniques have been used to investigate the structure of a 1 m aqueous solution of YCl3 at room temperature. Empirical potential structure refinement (EPSR) has been used to build a three dimensional model of the solution structure that is consistent with the bulk solvent correlations strongly probed by the neutron scattering technique. Optimization of the local structural environment of the Y3+ ion sites within the model has been performed through calculations of the yttrium K-edge, extended X ray absorption fine structure (EXAFS) spectrum of the solution, and detailed information has been extracted on the structure of the ion hydration shell and the extent of inner-sphere ion pairing within the solution. The results demonstrate the significant potential of this hybrid data analysis approach to circumvent the limitations of the individual experimental methods, to refine atomic potential models, and to produce accurate, quantitative structural models of the local environment of dilute atomic species within tightly constrained bulk network structures. PMID- 17850136 TI - Optimizing experimental parameters in isothermal titration calorimetry: variable volume procedures. AB - In the study of 1:1 binding, M + X right <==> MX, isothermal titration calorimetry is generally thought to be limited to reactions in which the key parameter, c = K[M]0, can be set in the range 1-1000. In fact, the range of applicability can be extended by a factor of 10-100 at the upper end and as much as 10(5) at the lower, with certain provisos. The present work emphasizes the low c regime, with the key heat parameter, h identical with DeltaH degrees [M]0, low, as well. Successful determination of K and DeltaH degrees in this region requires that the titration be extended to large excesses of titrant X over titrate M, and then the reaction heat is distributed strongly in favor of the early injections. With decreasing c, DeltaH degrees and the stoichiometry parameter n (often called site number) also become highly correlated and individually indeterminate. However, the product DeltaH degrees x n ( identical with Hn) is well-determined, so if n is known from other information, both K and DeltaH degrees can be determined to quite low c. By varying the titrant volume from injection to injection, one can significantly reduce the uncertainties in the estimated K and Hn values, permitting determination of K to better than 10% and Hn within 3% down to c = 10(-4), even for the low h value of 0.1 cal/L. The titrant volume optimization algorithm yields best results for the minimal number of injections - three when n is fitted, two when it is fixed. At low c, the resulting volume distributions depend nearly exponentially on injection number. This observation facilitates the derivation of similar, near-optimal volume distributions for five and four-injection procedures that offer two statistical degrees of freedom for analysis. The volume optimization results are tested on the Ba2+/18-crown-6 ether complexation reaction at c = 0.1 and h = 0.16 cal/L, illustrating some practical complications but confirming the utility of the variable-volume protocol. PMID- 17850137 TI - Structure and dynamics of lysozyme encapsulated in a silica sol-gel matrix. AB - Proteins entrapped in sol-gel matrices have been extensively studied during the last 15 years, showing that most of them can be encapsulated with retention of their native structure and functionality and with enhanced stability. However, relatively little is known about the structural and dynamical details of the biomolecule-matrix interactions. To achieve this goal, the model protein hen egg white lysozyme (HEWL) has been entrapped in sol-gel matrices prepared from tetraethyl orthosilicate through an alcohol-free sol-gel route, and the photophysical properties of its fluorescent tryptophans have been determined using both steady-state and time-resolved fluorescence techniques. By combining fluorescence spectra, quenching experiments, lifetimes, and time-resolved fluorescence anisotropy measurements, we have obtained information on the structure, dynamics, and solvation properties of the entrapped protein. Our results show that the environment of HEWL within the silica pore as well as its internal dynamics is similar to that in aqueous solution, except that the protein showed no or, depending on conditions, very much slower global motion but retained its internal angularly restricted (hindered) segmental rotation upon entrapment. The experiments carried out at different experimental conditions indicate that, below the isoelectric point of the protein, a strong electrostatic interaction is established between the protein molecule and the negatively charged sol-gel walls, which is ultimately responsible for the total arrest of the overall rotation of the protein, but without significant effect upon its segmental rotational relaxation. The electrostatic nature of the interaction is clearly established since either reducing the positive charge of the protein (by increasing the pH toward its isoelectric point) or increasing the ionic strength of the solution (shielding against the attractive interaction) leads to a situation in which the protein freely rotates within the matrix pore, albeit an order of magnitude more slowly than that in free solution under similar macroscopic solution conditions, and still retains its segmental rotational properties. PMID- 17850138 TI - Influence of molecular geometry on the adsorption orientation for oligophenylene ethynylenes on Au(111). AB - The adsorption structures formed from a class of oligophenylene-ethynylenes on Au(111) under ultrahigh vacuum conditions is compared based on high-resolution scanning tunneling microscopy (STM) measurements. The molecules consist of three or four benzene rings connected by ethynylene spokes and are all functionalized identically with an aldehyde, a hydroxyl, and a bulky tert-butyl group. Compounds with the conjugated spokes placed in the para, meta, and threefold configurations were previously found to exclusively form molecular layers with flat-lying adsorption geometries. In contrast, the associated compound with spokes in the ortho configuration surprisingly differs in its adsorption by forming only structures with an upright adsorption orientation. The packing density for the structures formed by the compound with the ortho configuration is less dense than that in conventional self-assembled monolayers while still keeping the conducting backbone in an upright orientation. These structures are thus interesting from the perspective of performing single-molecule conduction measurements on the oligophenylene-ethynylene backbones. PMID- 17850139 TI - Enhancement of conductivity by diameter control of polyimide-based electrospun carbon nanofibers. AB - Oxydianiline-pyromellitic dianhydride poly(amic acid) (ODA-PMDA PAA) was polymerized with a catalyst support of triethyl amine for controlling molecular weight. This polymer was used for electrospinning in the preparation of PAA nanofibers, a precursor of carbon nanofibers. Here the amount of catalyst and concentration of PAA solution were optimized to produce polyimide-based carbon nanofibers approximately 80 nm in diameter. The effects of molecular weight of PAA, bias voltage, and spinning rate on the morphology of electrospun PAA and polyimide nanofibers have been evaluated. We showed that the conductivity of the carbon nanofiber mat decreased with increasing nanofiber diameter, where the conductivity of polyimide-based carbon nanofiber mat was much higher than those of other types of carbon nanofiber mat. The key ingredient to increase conductivity in a carbon nanofiber mat was found to be the number of cross junctions between nanofibers. PMID- 17850140 TI - Copper(I) cyanide networks: synthesis, luminescence behavior and thermal analysis. Part 1. Diimine ligands. AB - Metal-organic networks of CuCN with diimines (L) = pyrazine (Pyz), 2 aminopyrazine (PyzNH(2)), quinoxaline (Qox), phenazine (Phz), 4,4'-bipyridyl (Bpy), pyrimidine (Pym), 2-aminopyrimidine (PymNH(2)), 2,4-diaminopyrimidine (Pym(NH(2))(2)), 2,4,6-triaminopyrimidine (Pym(NH(2))(3)), quinazoline (Qnz), pyridazine (Pdz), and phthalazine (Ptz) were studied. Open reflux reactions produced complexes (CuCN)(2)(L) for L = Qox, Phz, Bpy, PymNH(2), Pym(NH(2))(2), Qnz, and Pdz and (CuCN)(3)(L) complexes for L = Pyz, PyzNH(2), Qox, Bpy, Pym(NH(2))(3), and Pdz. Also produced were (CuCN)(3)(Pyz)(2), (CuCN)(PyzNH(2)), (CuCN)7(Pym)(2), (CuCN)(5)(Qnz)(2) and (CuCN)(5)(Ptz)(2). X-ray structures are presented for (CuCN)(2)(Pdz), (CuCN)(2)(PymNH(2)), and (CuCN)(7)(Pym)(2). Hydrothermal reactions yielded additional X-ray structures of (CuCN)(2)(PyzNH(2)), (CuCN)(3)(Pym(NH(2))(2)), (CuCN)(4)(Qnz), a second (CuCN)(2)(Pdz) phase, (CuCN)(5)(Pdz)2, (CuCN)(2)(Ptz), and (CuCN)(7)(Ptz)2. Structural trends, including cuprophilic interactions and cyano-bridged Cu(2)(CN)(2) dimer formation, are discussed. Particularly short Cu...Cu interactions are noted for the novel 4- and 5-coordinate Cu(2)(CN)(2) dimers. Thermal analyses show that most of the complexes decompose with loss of L around 160-180 degrees C. Luminescence behavior is relatively weak in the products. PMID- 17850141 TI - Synthesis, structural characterization, and biological studies of new antimony(III) complexes with thiones. The influence of the solvent on the geometry of the complexes. AB - Five new antimony(III) complexes with the heterocyclic thiones 2-mercapto benzimidazole (MBZIM), 5-ethoxy-2-mercapto-benzimidazole (EtMBZIM), and 2 mercapto-thiazolidine (MTZD) of formulas {[SbCl(2)(MBZIM)4]+.Cl-.2H(2)O. (CH(3)OH)} (1), {[SbCl(2)(MBZIM)4]+.Cl-.3H(2)O.(CH3CN)} (2), [SbCl(3)(MBZIM)2] (3), [SbCl(3)(EtMBZIM)(2)] (4), and [SbCl(3)(MTZD)2] (5) have been synthesized and characterized by elemental analysis, FT-IR, far-FT-IR, differential thermal analysis-thermogravimetry, X-ray diffraction, and conductivity measurements. Complex {[SbCl2(tHPMT)(2)]+Cl-}, (tHPMT = 2-mercapto-3,4,5,6-tetrahydro pyrimidine), already known, was also prepared, and its X-ray crystal structure was solved. It is shown that the complex is better described as {[SbCl3(tHPMT)(2)]} (6). Crystal structures of all other complexes (1-5) have also been determined by X-ray diffraction at ambient conditions. The crystal structure of the hydrated ligand, EtMBZIM.H2O is also reported. Compound [C(28)H(24)Cl(2)N(8)S(4)Sb.2H(2)O.Cl.(CH(3)OH)] (1) crystallizes in space group P2(1), with a = 7.7398(8) A, b = 16.724(3) A, c = 13.717(2) A, beta = 98.632(11) degrees, and Z = 2. Complex [C(28)H(24)Cl(2)N(8)S(4)S(b).Cl.3H(2)O.(CH(3)CN)] (2) corresponds to space group P2(1), with a = 7.8216(8) A, b = 16.7426(17) A, c = 13.9375(16) A, beta = 99.218(10) degrees , and Z = 2. In both 1 and 2 complexes, four sulfur atoms from thione ligands and two chloride ions form an octahedral (Oh) cationic [SbS(4)Cl(2)]+ complex ion, where chlorides lie at axial positions. A third chloride counteranion neutralizes it. Complexes 1 and 2 are the first examples of antimony(III) compounds with positively charged Oh geometries. Compound [C(14)H(12)Cl(3)N(4)S(2)S(b)] (3) crystallizes in space group P, with a = 7.3034(5) A, b = 11.2277(7) A, c = 12.0172(8) A, alpha = 76.772(5) degrees, beta = 77.101(6) degrees, gamma = 87.450(5) degrees, and Z = 2. Complex [C(18)H(20)Cl(3)N(4)O(2)S(2)S(b)] (4) crystallizes in space group P1, with a = 8.6682(6) A, b = 10.6005(7) A, c = 13.0177(9) A, alpha = 84.181(6) degrees, beta = 79.358(6) degrees, gamma = 84.882(6) degrees, and Z = 2, while complex [C(6)H(10)Cl(3)N(2)S(4)S(b)] (5) in space group P2(1)/c shows a = 8.3659(10) A, b = 14.8323(19) A, c = 12.0218(13) A, beta = 99.660(12) degrees, and Z = 4 and complex [C(8)H(16)Cl(3)N(4)S(2)S(b)] (6) in space group P1 shows a = 7.4975(6) A, b = 10.3220(7) A, c = 12.1094(11) A, alpha = 71.411(7) degrees, beta = 84.244(7) degrees, gamma = 73.588(6) degrees, and Z = 2. Crystals of complexes 3-6 grown from acetonitrile solutions adopt a square-pyramidal (SP) geometry, with two sulfur atoms from thione ligands and three chloride anions around Sb(III). The equatorial plane is formed by two sulfur and two chloride atoms in complexes 3-5, in a cis-S, cis-Cl arrangement in 3 and 5 and a trans-S, trans-Cl arrangement in 4. Finally, in the case of 6, the equatorial plane is formed by three chloride ions and one sulfur from the thione ligand while the second sulfur atom takes an axial position leading to a unique SP conformation. The complexes showed a moderate cytostatic activity against tumor cell lines. PMID- 17850142 TI - Importance of counterion reactivity on the deactivation of Co-salen catalysts in the hydrolytic kinetic resolution of epichlorohydrin. AB - Possible modes of deactivation of Jacobsen's Co-salen catalyst during the hydrolytic kinetic resolution (HKR) of epichlorohydrin were explored by UV-vis spectroscopy, X-ray absorption spectroscopy, and electrospray ionization mass spectrometry, combined with recycling studies. Although an active Co(III)-salen catalyst deactivated substantially after multiple cycles without regeneration, the catalyst maintained its +3 oxidation state throughout the runs. Thus, deactivation of Co-salen during HKR was not the result of Co reduction. The mass spectrum of a deactivated material showed that catalyst dimerization does not account for the loss of activity. Results from various catalyst pretreatment tests, as well as from catalysts containing various counterions (acetate, tosylate, chloride, iodide) indicated that the rate of addition of the Co-salen counterions to epoxide forming Co-OH during the reaction correlated with deactivation. The extent of counterion addition to epoxide was influenced by the exposure time and the nucleophilicity of the counterion. An oligo(cyclooctene) supported Co-OAc salen catalyst, which was 25 times more active than the standard Co-salen catalyst, was recycled multiple times with negligible deactivation. PMID- 17850143 TI - Bifunctional amine-tethered ruthenium(II) arene complexes form monofunctional adducts on DNA. AB - The tethered RuII half-sandwich complexes [eta(6):eta(1) C(6)H(5)(CH(2))(n)NH(2))RuCl(2)] 1 (n = 3) and 2 (n = 2) have been synthesized as potential bifunctional anticancer complexes, and their X-ray crystal structures have been determined. They hydrolyze rapidly in aqueous solution to give predominantly mono-aqua mono-chlorido species. Mono-9EtG adducts, where 9EtG = 9 ethylguanine, form rapidly, but the second 9EtG binds more slowly and more weakly. In the X-ray crystal structure of the di-9EtG adduct [(eta(6):eta(1) C(6)H(5)(CH(2))(3)NH(2))Ru(9EtG)2](CF(3)SO(3))(2).H(2)O (8.H(2)O), one of the Ru N7 bonds is significantly longer than the other (2.1588(18) vs 2.101(2) A). The bound guanine bases adopt a head-to-head configuration, stabilized by tether NH2 hydrogen bonding to C6O of 9EtG. The X-ray crystal structure of the dinitrato complex [(eta(6):eta(1)-C(6)H(5)(CH(2))(3)NH(2))Ru(NO(3))(2)] (3) showed both nitrates to be bound to ruthenium. This complex readily rutheniated calf thymus DNA but failed to produce stop sites on pSP73KB plasmid DNA during DNA transcription by an RNA polymerase. This suggested that only monofunctional DNA adducts formed, as did interstrand cross-linking assays. Also, the unwinding angle induced in negatively supercoiled DNA (9 +/- 1 degrees) was less than that induced by cisplatin (13 degrees). These findings may explain why complexes such as 1 and 2 exhibited low cytotoxicities (IC(50) values >100 microM) toward A2780 human ovarian cancer cells. PMID- 17850144 TI - [CH3NH2(CH2)2NH2CH3][M2(HCOO)6] (M = MnII and CoII): weak ferromagnetic metal formate frameworks of unique binodal 6-connected (4(12).6(3))(4(9).6(6)) topology, templated by a diammonium cation. AB - Two compounds of [dmenH(2)(2+)][M(2)(HCOO)(6)(2-)] (M = Mn(II) and Co(II)), synthesized using N,N'-dimethylethylenediammonium (dmenH(2)(2+)) as the template, possess anionic metal formate frameworks of a novel binodal 6-connected (4(12).6(3))(4(9).6(6)) topology. They are the first coordination examples of this unique network closely related to niccolite and colquiriite and exhibit 3D long-range antiferromagnetic ordering with small spin canting. PMID- 17850145 TI - Eu3(AsS4)2 and AxEu(3-y)As(5-z)S10 (A = Li, Na): compounds with simple and complex thioarsenate building blocks. AB - Eu(3)(AsS(4))(2) and A(x)Eu(3-y)As(5-z)S(10) (A = Li, Na) are the members of a new thioarsenate family. They feature As(5+) and As(3+) centers, respectively. The rhombohedral Eu(3)(AsS(4))(2) features a new structure type consisting of eight-coordinate Eu(2+) centers and AsS(4)(3-) anions, whereas the monoclinic A(x)Eu(3-y)As(5-z)S(10) (Li(0.73)Eu(3)As(4.43)S(10) and Na(0.66)Eu(2.86)As(4.54)S(10)) belong to the rathite sulfosalt family and are comprised of apparent [As(10)S(20)](10-) segments linked with Eu(2+) ions to give a three-dimensional network. They appear to be alkali-metal-stabilized derivatives of the putative parent phase "Eu(3)As(5)S(10)". PMID- 17850146 TI - Ferrimagnetic FeIII-MnIII zigzag chain formed by a new mer-positioned ironIII cyanide precursor. AB - A new cyanide-bearing molecular precursor, mer-[Fe(pzcq)(CN)(3)]- (1), and a zigzag chain, [Fe(pzcq)(CN)(3)][Mn(salen)].4H(2)O (2), were prepared and characterized in terms of structure and magnetism. Magnetic data reveal that intrachain antiferromagnetic couplings via cyanide ligands in 2 are clearly operating, resulting in a ferrimagnetic nature. PMID- 17850147 TI - Phenomenon of optical self-purification of chiral non-racemic compounds. PMID- 17850148 TI - Fluorescence amplification by electrochemically deposited silver nanowires with fractal architecture. AB - Electrochemically deposited silver structures with nanowires 50-100 nm in diameter show high fluorescence amplification and strongly reduced fluorescence lifetimes. Both quantities depend on the structure thickness. With increasing thickness the fluorescence amplification proportionally increases and the fluorescence lifetime decreases. This thickness dependence is caused by fluorophore interaction with a system of plasmon excitations in coupled nanowires extending over micrometer size regions. Thus the amplification is attributed to a combination of extended structure area and strong plasmonic coupling between nanowires which also help to radiatively scatter the fluorescence emission. PMID- 17850149 TI - Surface-assisted assembly of an ionic-complementary peptide: controllable growth of nanofibers. AB - Numerous studies have shown that a surface can direct and regulate molecular assembly. In this study, the nanofiber growth of an ionic-complementary peptide, EAK16-II, on a mica surface was investigated under various solution conditions via in situ atomic force microscopy. In comparison to the assembly in bulk solution, nanofiber growth of EAK16-II on mica is surface-assisted and involves two steps: (1) adsorption of nanofibers and fiber clusters (from the bulk solution) on the surface, serving as the "seeds"; (2) fiber elongation of the "seeds" from their active ends. The nanofiber growth can be controlled by adjusting the solution pH since it modulates the adsorption of the "seeds" on mica and their growth rates. The amount of the adsorbed "seeds" decreases with increasing solution pH, while the growth rate under different solution conditions is found to follow the order pure water > 1 mM HCl > 1 mM NaOH > 10 mM HCl approximately 10 mM NaOH approximately 0. The pH-dependent nanofiber growth is due to the surface charge of the peptides and peptide assemblies in various solutions as indicated by zeta-potential measurements. A simple model was proposed to describe surface-assisted nanofiber growth. This study provides insights into the assembly of peptide/protein on a surface, which is essential to understand such physiological protein aggregation systems as amyloid fibrillogenesis. In addition, the potential of this finding to construct biocompatible electrodes for biomolecular sensing is also discussed. PMID- 17850150 TI - Regioselective oxidative cation-olefin cyclization of poly-enes: catalyst turnover via hydride abstraction. PMID- 17850151 TI - Borate binding to siderophores: structure and stability. AB - Well-known as specific iron chelating agents produced by bacteria, it is shown that some, but not all, siderophore classes have an unexpected binding affinity for boron. The relevant criterium is the availability of a vicinal dianionic oxygen containing binding group (i.e., citrate or catecholate). The resulting boron complexes have been characterized by ESI-MS, multinuclear NMR, and DFT calculations. Detailed boron binding constants have been measured for vibrioferrin, rhizoferrin, and petrobactin. The observed affinity of certain siderophores for borate, a common chemical species in the marine but not the terrestrial environment, allows for small, but potentially significant, concentrations of B-siderophores to exist at oceanic pH. We hypothesize that these concentrations could be sufficient for them to function as cell signaling molecules or as mediators of biological boron uptake. In addition, binding of the tetrahedral boron to these siderophores results in a conformation that is different from either the free siderophore or its iron complex and would thus allow a distinction to be made between its iron uptake and any putative cell signaling roles. PMID- 17850152 TI - Directed hydrozirconation of propargylic alcohols. PMID- 17850153 TI - Isatisine A, a novel alkaloid with an unprecedented skeleton from leaves of Isatis indigotica. AB - 9alpha,13alpha-Dihydroxylisopropylidenylisatisine A (1), which was derived from isatisine A (2) and possessed an unprecedented fused pentacyclic skeleton, was isolated from the leaves of Isatis indigotica Fort. The structure and relative configuration were elucidated on the basis of extensive NMR analyses and finally determined by single-crystal X-ray diffraction. Compound 1 showed moderate anti HIV-1 activity with EC50 = 37.8 microM and SI = 7.98. PMID- 17850154 TI - From simple Ugi adducts to indanes and delta-amidomalonates: new manganese(III) induced radical cascades. AB - A complete change of the traditional Ugi adducts framework has been obtained using new radical cascades as Ugi post-condensation reactions. Indanes and delta amidomalonates were thus obtained in a one-pot procedure from aromatic aldehydes under a sequence involving Ugi addition followed by treatment of the adducts with Mn(III) and malonate or beta-ketoester. The radical step probably involves an intramolecular aryl transfer followed by an oxidative cleavage and final cyclization to indanes. PMID- 17850155 TI - Thin film organic transistors from air-stable heteroarenes: anthra[1,2-b:4,3 b':5,6-b'':8,7-b''']tetrathiophene derivatives. AB - A facile synthesis of air-stable anthra[1,2-b:4,3-b':5,6-b'':8,7 b''']tetrathiophene derivatives 1a and 1b has been developed for applications in organic thin film transistors. Both molecules tend to self-associate through pi pi stacking in solution and in different films. The hole mobility of 0.012 cm2 V( 1) s(-1) is obtained from 1a due to morphology changes in films from less ordered to highly ordered structures after thermal annealing. Good performance remained persistent over a period of 14 days, indicating the high stability of such transistors. PMID- 17850156 TI - Enantioselective Pd-catalyzed allylic alkylation of indoles by a new class of chiral ferrocenyl P/S ligands. AB - Chiral ferrocenyl heterobidentate P/S ligands bearing both central and planar chirality were prepared from (S)-Ugi's amine via a three-step modular synthesis. Through systematic screening and optimization, L8 was found to be the best ligand for Pd-catalyzed asymmetric allylic alkylation of indoles with ee's up to 96% being attained. PMID- 17850158 TI - Dynamic decomposition/recombination of hydrogen bonds in molecular duplex strands. AB - Dynamic decomposition/recombination of hydrogen bonds in the hydrazide based molecular duplex strands was explored by variable-temperature 1H NMR experiments. A shuttle-like dynamic process of the two constituent molecules of the duplex strands between two degenerate states was observed. PMID- 17850157 TI - Formation of ternary complexes between a macrotricyclic host and hetero-guest pairs: an acid-base controlled selective complexation process. AB - A triptycene-based cylindrical macrotricyclic host can include diquat and electron-rich aromatics simultaneously to form stable ternary complexes, which is stabilized not only by a charge-transfer (CT) interaction between electron-rich and electron-deficient guests but also by the face to face pi-stacking interactions between the host and the guests. Moreover, a selective complexation process between a ternary complex containing benzidine and a binary complex can be effectively controlled by the use of acid and base. PMID- 17850159 TI - Intramolecular palladium-catalyzed direct arylation of alkenyl triflates. AB - A catalyst generated from Pd(OAc)2 and dppp is effective for the direct intramolecular arylation of alkenyl triflates. Conjugated alkene-arene-containing carbocycles are produced in good yield. The process tolerates a variety of aryl substituents as well a simple heteroaryl groups. Electron-deficient aryl rings deliver faster reactions. PMID- 17850160 TI - The first example of a diastereoselective thio-Ugi reaction: a new synthetic approach to chiral imidazole derivatives. AB - The first example of a diastereoselective thio-Ugi reaction with chiral alpha methylbenzylamine is described. The reaction results in formation of two diastereomers of thioamides, the major of which was isolated. We have found that under similar conditions stereochemical results of the thio-Ugi reaction are opposite to stereochemical results of the Ugi reaction. Several chiral thioamides were synthesized. The reaction of thioamides with ammonia results in substituted amidines, which can be cyclized to imidazole derivatives in aqueous HCl. The synthesis of chiral imidazole derivatives was elaborated. Using certain approaches, both isomers of a key synthon in the synthesis of SB203386 (an orally bioactive HIV-1 protease inhibitor) were prepared. The scope, limitations, and stereochemistry of the approach are discussed. PMID- 17850162 TI - Characterization of equatorial and axial six-membered-ring peroxyl radicals. AB - Spectroscopic data are consistent with computations that show that, in their most stable conformations, the peroxyl moiety is equatorial in cyclohexylperoxyl radicals and axial in oxa- and most polyoxacyclohexyl-2-peroxyl radicals. PMID- 17850161 TI - Diastereoselective Prins-type reaction of cycloalkenylcyclopropanol silyl ethers and alpha,beta-unsaturated aldehyde acetals. AB - Electrophilic addition of 1-(1-cyclohexenyl)-1-cyclopropanol trimethylsilyl ether to alpha,beta-unsaturated aldehyde acetals under Lewis acidic conditions proceeds with good to excellent diastereoselectivity to afford spirocyclobutanones containing three contiguous stereocenters. A convenient entry to enantioselective syntheses is available by use of a nonracemic C2-symmetric acetal. Elaboration of the resulting adducts provides ready access to medium-sized carbocycles. PMID- 17850163 TI - Extending Pummerer reaction chemistry. Synthesis studies in the phakellin alkaloid area. AB - The syntheses of (+/-)-dibromophakellstatin and, from this species, (+/-) dibromophakellin are described. Oxidative cyclization of a phenylthiolated dihydrooroidin derivative triggered by a Pummerer reaction constitutes the key step in this biomimetic approach to this family of marine alkaloids. PMID- 17850164 TI - Hydrogen storage in molecular clathrates. PMID- 17850165 TI - Structure/function relationships of [NiFe]- and [FeFe]-hydrogenases. PMID- 17850166 TI - Comment on high-quality luminescent tellurium nanowires of several nanometers in diameter and high aspect ratio synthesized by a poly (vinyl pyrrolidone)-assisted hydrothermal process. PMID- 17850167 TI - Chemical force microscopy of single live cells. AB - Traditionally, cell surface properties have been difficult to study at the subcellular level, especially on hydrated, live cells. Here, we demonstrate the ability of chemical force microscopy to map the hydrophobicity of single live cells with nanoscale resolution. After validating the technique on reference surfaces with known chemistry, we probe the local hydrophobic character of two medically important microorganisms, Aspergillus fumigatus and Mycobacterium bovis, in relation with function. Applicable to a wide variety of cells, the chemically sensitive imaging method presented here provides new opportunities for studying the nanoscale surface properties of live cells and for understanding their roles in mediating cellular events. PMID- 17850168 TI - Hydrogen storage in Pd nanodisks characterized with a novel nanoplasmonic sensing scheme. AB - A novel nanoplasmonic sensing scheme is introduced based on remote real-time detection of induced electronic and shape/structural changes in a metal nanoparticle during the metal-hydride formation process. The localized surface plasmon resonance (LSPR) of the nanoparticle is utilized as signal transducer for optical readout. As a model system, hydrogen storage through metal-hydride formation is studied in Pd nanodisks. The experimentally obtained plasmonic response to hydrogen uptake yields pressure-LSPR-response isotherms. These isotherms are found to obey Sievert's law in the low-pressure range and exhibit a characteristic "plateau" at 18 Torr upon hydrogen charging and 7.5 Torr upon hydrogen discharging. An additional experiment also clearly shows the typical temperature dependence of the plateau pressure. Conversion of the LSPR signal to absolute hydrogen concentration, based on a proposed linear dependence of the LSPR response to hydrogen uptake, results in p-C isotherms in excellent agreement with those in the literature. This puts forward that the LSPR response is an extremely sensitive, remote, and real-time probe for "bulk" changes in a metal nanoparticle and can readily be used to study processes such as metal-hydride formation for hydrogen storage applications, alloying on the nanoscale, thermal reshaping, and so forth. PMID- 17850169 TI - The role of anti-inflammatory agents in Parkinson's disease. AB - There is ample and increasing evidence, from studies of human pathology, animal models and tissue culture, that chronic inflammation occurs in the basal ganglia in patients with Parkinson's disease. In such inflammatory states, activated glia can produce large quantities of free radicals and other neurotoxic materials. Dopaminergic neurons appear to be particularly vulnerable to these neurotoxins. The anti-inflammatory drugs that are presently in wide use act on peripheral players in the inflammatory process. Many experiments are under way to find agents that inhibit more potent contributors, such as the activated microglia or terminal complement proteins. Whether such drugs will slow the process of Parkinson's disease or reduce the high risk of dementia in such patients remains to be determined in future work. PMID- 17850170 TI - Hashimoto's encephalopathy : epidemiology, pathogenesis and management. AB - Hashimoto's encephalopathy is a term used to describe an encephalopathy of presumed autoimmune origin characterised by high titres of antithyroid peroxidase antibodies. In a similar fashion to autoimmune thyroid disease, Hashimoto's encephalopathy is more common in women than in men. It has been reported in paediatric, adult and elderly populations throughout the world. The clinical presentation may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms and myoclonus. Thyroid function is usually clinically and biochemically normal.Hashimoto's encephalopathy appears to be a rare disorder, but, as it is responsive to treatment with corticosteroids, it must be considered in cases of 'investigation negative encephalopathies'. Diagnosis is made in the first instance by excluding other toxic, metabolic and infectious causes of encephalopathy with neuroimaging and CSF examination. Neuroimaging findings are often not helpful in clarifying the diagnosis. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and nonparaneoplastic limbic encephalitis. In the context of the typical clinical picture, high titres of antithyroid antibodies, in particular antithyroid peroxidase antibodies, are diagnostic. These antibodies, however, can be detected in elevated titres in the healthy general population. Treatment with corticosteroids is almost always successful, although relapse may occur if this treatment is ceased abruptly. Other forms of immunomodulation, such as intravenous immune-globulin and plasma exchange, may also be effective. Despite the link to autoimmune thyroid disease, the aetiology of Hashimoto's encephalopathy is unknown. It is likely that antithyroid antibodies are not pathogenic, but titres can be a marker of treatment response. Pathological findings can suggest an inflammatory process, but features of a severe vasculitis are often absent. The links between the clinical pictures, thyroid disease, auto antibody pattern and brain pathology await further clarification through research. It may be that Hashimoto's encephalopathy will be subsumed into a group of nonvasculitic autoimmune inflammatory meningoencephalopathies. This group may include disorders such as limbic encephalitis associated with voltage-gated potassium channel antibodies. Some authors have suggested abandoning any link to Hashimoto and renaming the condition 'steroid responsive encephalopathy associated with autoimmune thyroiditis' to better reflect current, if limited, understanding of this condition. PMID- 17850171 TI - Mechanisms underlying postoperative nausea and vomiting and neurotransmitter receptor antagonist-based pharmacotherapy. AB - Postoperative nausea and vomiting (PONV) is one of the most common and distressing complications following surgery, and understanding the mechanism(s) underlying PONV is essential to providing optimal prophylaxis and/or treatment of PONV. The knowledge base of PONV physiology has significantly expanded over the past decade. This article reviews the risk factors for the development of PONV and the mechanisms of action of pharmacological agents (including antagonists of serotonin 5-HT(3), dopaminergic D(2), histamine H(1), muscarinic cholinergic, opioid and neurokinin NK(1) receptors) for the management (i.e. prophylaxis and treatment) of PONV. NK(1) receptor antagonists, with their unique mechanism of action, are a particularly promising area of research as they appear to be efficacious in preventing PONV during both the early and the late postoperative periods. A successful PONV management strategy includes: (i) identifying patients at risk; (ii) keeping the baseline risk low; and (iii) using a combination of antiemetics acting on different receptors in moderate- to high-risk patients. PMID- 17850172 TI - Ziprasidone for the treatment of acute manic or mixed episodes associated with bipolar disorder. AB - Ziprasidone, a benzisothiazolyl piperazine-type atypical antipsychotic agent, has a unique receptor-binding profile. A potent antagonist of serotonin 5-HT(2A) and dopamine D(2) receptors, ziprasidone has an affinity for 5-HT(2A) receptors >10 fold higher than its affinity for D(2) receptors. Ziprasidone has been shown to be effective in the treatment of bipolar disorder in patients experiencing manic or mixed episodes. It was significantly more effective than placebo in improving manic symptoms as early as day 2 of treatment in two 3-week placebo-controlled trials as monotherapy. In a 12-week, placebo-controlled trial of patients with acute mania, ziprasidone as monotherapy showed comparable efficacy with, and fewer movement-related adverse events than, haloperidol. It has demonstrated efficacy in two 1-year open-label extension trials, both as monotherapy and in combination with lithium. Ziprasidone has a generally favourable adverse effect profile. In short-term placebo-controlled trials, there were similar discontinuation rates in active treatment and placebo recipients. While twice as many patients treated with ziprasidone compared with placebo discontinued therapy because of adverse events, the number of events was small and adverse effects were generally mild or moderate. The favourable tolerability of ziprasidone has been confirmed in long-term extension studies and its use was not associated with weight gain or dyslipidaemia. Ziprasidone-related movement disorders occurred infrequently. PMID- 17850174 TI - Subcutaneous interferon-beta-1a : new formulation. AB - The new formulation of subcutaneous interferon-beta-1a was developed without serum-derived components with the aim of improving immunogenicity and injection tolerability in patients with relapsing forms of multiple sclerosis (MS). In a prospectively defined interim analysis at 48 weeks of an ongoing, single-arm, phase IIIb trial, 13.9% of MS patients receiving the new formulation of subcutaneous interferon-beta-1a 44 microg three times weekly had developed neutralising antibodies (NAbs). In the EVIDENCE trial, which served as an historical control, 24.4% of patients receiving the same dosage of the current formulation had developed NAbs at 48 weeks. The new formulation demonstrated similar pharmacokinetic activity to that of the current formulation in a phase I, double-blind, placebo-controlled study in healthy volunteers. About two-thirds of patients with MS who received the new formulation of subcutaneous interferon-beta 1a were relapse free in the interim, 48-week analysis of the single-arm trial; this is similar to results for the current formulation from historical data. A comparison of results from the interim, 48-week analysis with historical-control data from the EVIDENCE trial indicates that the new formulation of interferon beta-1a may be associated with a lower incidence of injection-site reactions and a higher incidence of influenza-like symptoms than the current formulation. Adverse events associated with the new formulation were mostly mild to moderate in severity PMID- 17850175 TI - Grand challenges in global health: the ethical, social and cultural program. PMID- 17850173 TI - Biological treatments for amfetamine dependence : recent progress. AB - Amfetamine abuse has grown into a worldwide epidemic. Methamfetamine, a derivative of amfetamine made from readily accessible chemicals, has plagued the US since the 1960s, with an alarming recent surge in the numbers of those meeting the criteria for amfetamine abuse and dependence. We review this problem using a computerised literature search (PubMed 1964-2007) to summarise knowledge from animal and human studies about treatments for amfetamine dependence, while exploring the potential of pharmacogenetics to help uncover new treatment targets. Several promising therapeutic targets have come from animal models of reward, drug-taking behaviour and withdrawal. Although preclinical and selected clinical results have been promising, clinical studies have yielded inconsistent results. To improve these outcomes, pharmacogenetic studies may be used to identify candidate alleles that predict therapeutic response. Exciting preclinical findings and a steady progression of clinical results offer hope for the development of a treatment for amfetamine dependence. PMID- 17850176 TI - Grand challenges in global health: ethical, social, and cultural issues based on key informant perspectives. PMID- 17850177 TI - Grand challenges in global health: engaging civil society organizations in biomedical research in developing countries. PMID- 17850178 TI - Grand challenges in global health: community engagement in research in developing countries. PMID- 17850179 TI - BDCA2/Fc epsilon RI gamma complex signals through a novel BCR-like pathway in human plasmacytoid dendritic cells. AB - Dendritic cells are equipped with lectin receptors to sense the extracellular environment and modulate cellular responses. Human plasmacytoid dendritic cells (pDCs) uniquely express blood dendritic cell antigen 2 (BDCA2) protein, a C-type lectin lacking an identifiable signaling motif. We demonstrate here that BDCA2 forms a complex with the transmembrane adapter Fc epsilon RI gamma. Through pathway analysis, we identified a comprehensive signaling machinery in human pDCs, similar to that which operates downstream of the B cell receptor (BCR), which is distinct from the system involved in T cell receptor (TCR) signaling. BDCA2 crosslinking resulted in the activation of the BCR-like cascade, which potently suppressed the ability of pDCs to produce type I interferon and other cytokines in response to Toll-like receptor ligands. Therefore, by associating with Fc epsilon RI gamma, BDCA2 activates a novel BCR-like signaling pathway to regulate the immune functions of pDCs. PMID- 17850180 TI - High-throughput in vivo analysis of gene expression in Caenorhabditis elegans. AB - Using DNA sequences 5' to open reading frames, we have constructed green fluorescent protein (GFP) fusions and generated spatial and temporal tissue expression profiles for 1,886 specific genes in the nematode Caenorhabditis elegans. This effort encompasses about 10% of all genes identified in this organism. GFP-expressing wild-type animals were analyzed at each stage of development from embryo to adult. We have identified 5' DNA regions regulating expression at all developmental stages and in 38 different cell and tissue types in this organism. Among the regulatory regions identified are sequences that regulate expression in all cells, in specific tissues, in combinations of tissues, and in single cells. Most of the genes we have examined in C. elegans have human orthologs. All the images and expression pattern data generated by this project are available at WormAtlas (http://gfpweb.aecom.yu.edu/index) and through WormBase (http://www.wormbase.org). PMID- 17850181 TI - Variants in a novel epidermal collagen gene (COL29A1) are associated with atopic dermatitis. AB - Atopic dermatitis (AD) is a common chronic inflammatory skin disorder and a major manifestation of allergic disease. AD typically presents in early childhood often preceding the onset of an allergic airway disease, such as asthma or hay fever. We previously mapped a susceptibility locus for AD on Chromosome 3q21. To identify the underlying disease gene, we used a dense map of microsatellite markers and single nucleotide polymorphisms, and we detected association with AD. In concordance with the linkage results, we found a maternal transmission pattern. Furthermore, we demonstrated that the same families contribute to linkage and association. We replicated the association and the maternal effect in a large independent family cohort. A common haplotype showed strong association with AD (p = 0.000059). The associated region contained a single gene, COL29A1, which encodes a novel epidermal collagen. COL29A1 shows a specific gene expression pattern with the highest transcript levels in skin, lung, and the gastrointestinal tract, which are the major sites of allergic disease manifestation. Lack of COL29A1 expression in the outer epidermis of AD patients points to a role of collagen XXIX in epidermal integrity and function, the breakdown of which is a clinical hallmark of AD. PMID- 17850183 TI - Developing, validating and using test batteries and tiered (hierarchical) testing schemes. PMID- 17850182 TI - High-resolution genome-wide dissection of the two rules of speciation in Drosophila. AB - Postzygotic reproductive isolation is characterized by two striking empirical patterns. The first is Haldane's rule--the preferential inviability or sterility of species hybrids of the heterogametic (XY) sex. The second is the so-called large X effect--substitution of one species's X chromosome for another's has a disproportionately large effect on hybrid fitness compared to similar substitution of an autosome. Although the first rule has been well-established, the second rule remains controversial. Here, we dissect the genetic causes of these two rules using a genome-wide introgression analysis of Drosophila mauritiana chromosome segments in an otherwise D. sechellia genetic background. We find that recessive hybrid incompatibilities outnumber dominant ones and that hybrid male steriles outnumber all other types of incompatibility, consistent with the dominance and faster-male theories of Haldane's rule, respectively. We also find that, although X-linked and autosomal introgressions are of similar size, most X-linked introgressions cause hybrid male sterility (60%) whereas few autosomal introgressions do (18%). Our results thus confirm the large X effect and identify its proximate cause: incompatibilities causing hybrid male sterility have a higher density on the X chromosome than on the autosomes. We evaluate several hypotheses for the evolutionary cause of this excess of X-linked hybrid male sterility. PMID- 17850184 TI - The selection of serum-independent PC12 cells for a more-reliable manganese cytotoxicity test. AB - A major issue concerning the protocols of heavy metal cytotoxicity tests with PC12 cells was the hypothesis that serum in the culture medium might sequester the metal, thus altering the results obtained. However, serum withdrawal impairs the viability of PC12 cells themselves, thus impeding cytotoxicity testing in the absence of serum. In this study, we repeatedly selected undifferentiated, totally non-adherent PC12 cells in Petri dishes. Surprisingly, we discovered that these cells could survive and proliferate in serum-free medium. Moreover, features such as NGF-responsiveness, resazurin reduction potential, doubling rate, protein content, and basal caspase-3 enzyme activity, were equivalent to those exhibited by standard PC12 cultures. Further experiments aimed at fully characterising these serum-independent PC12 cells are in progress. These cells enabled cytotoxicity experiments to be conducted with manganese, both in serum supplemented and in serum-deprived medium. The results demonstrated that serum removal decreased the LC50 of manganese from 250microM to 32microM, without affecting the internalisation of the metal. The data exclude an early competitive effect of serum on metal internalisation; rather, they suggest a late protective mechanism mediated by serum against the cytotoxic effect of the already internalised metal. PMID- 17850185 TI - In vitro effects of certain membrane-acting agents on superoxide and hydrogen peroxide production, protein synthesis and membrane ATPase activity in buffalo PMN cells. AB - Polymorphonuclear (PMN) cells play a key role in innate immunity, due to their ability to produce reactive oxidants such as superoxide (O(2-)) and hydrogen peroxide (H(2)O(2)), and to release antimicrobial proteins and peptides stored in their lysosomal granules. In the present study, the effects of the activation of buffalo PMN cells with various membrane-acting agents were evaluated in terms of O(2-) and H(2)O(2) production, the activities of membrane ATPases, and protein synthesis. Studies involving the incorporation of (35)S-methionine revealed significant protein-synthesising ability in resting PMN cells and in cells treated with lipopolysaccharide (LPS), as well as with opsonised zymosan (OZ). Protein synthesis, as judged by fluorography of the cytosolic fraction, showed more than 12 bands, whilst the cytoskeletal fraction showed 2-3 bands. PMN activation with concanavalin A (ConA), digitonin and sodium nitroprusside (SNP) resulted in increased O(2-) and H(2)O(2) production. However, in the presence of anti-inflammatory agents such as indomethacin and cortisol, the production of O(2 ) and H(2)O(2) by these cells was found to decline. Studies pertaining to membrane ATPases revealed that verapamil hydrochloride (VpHCl) significantly increased total ATPase and Na(+)K(+)ATPase activity. ConA treatment yielded only a moderate level of activity. Similarly, digitonin up to 24microM also caused a significant increase in ATPase activity. Our observations indicate that these membrane-acting agents influenced oxygen-dependent and oxygen-independent microbicidal mechanisms in buffalo PMN cells. PMID- 17850186 TI - A statistical model to allow the phasing out of the animal testing of demineralised bone matrix products. AB - Demineralised bone matrix (DBM) products are complex mixtures of proteins known to influence bone growth, turnover, and repair. They are used extensively in orthopaedic surgery, and are bioassayed in vivo prior to being used in clinical applications. Many factors contribute to the osteogenic potency of DBM, but the relative contributions of these factors, as well as the possibility of interactive effects, are not completely defined. The "gold standard" measure of the therapeutic value of DBM, the in vivo assay for ectopic bone formation, is costly, time-consuming, and involves the use of numerous animal subjects. We have measured the levels of five growth factors released by the collagenase digestion of DBM, and statistically related these levels with osteogenic potency as determined by a standard in vivo model, in order to determine which value or combination of values of growth factors best predict osteogenic activity. We conclude that the level of BMP-2 is the best single predictor of osteogenic potency, and that adding the values of other growth factors only minimally increases the predictive power of the BMP-2 measurement. A small, but significant, interactive effect between BMP-2 and BMP-7 was demonstrated. We present a statistical model based on growth factor (e.g. BMP-2) analysis that best predicts the in vivo assay score for DBM. This model allows the investigator to predict which lots of DBM are likely to exhibit in vivo bioactivity and which are not, thus reducing the need to conduct in vivo testing of insufficiently active lots of DBM. This model uses cut-point analysis to allow the user to assign an estimate of acceptable uncertainty with respect to the "gold standard" test. This procedure will significantly reduce the number of animal subjects used to test DBM products. PMID- 17850187 TI - Prediction of acute toxicity in HPCT-1E3 hepatocytoma cells with liver-like transport activities. AB - A battery of in vitro methods has been developed for the prediction of acute oral toxicity, to reduce the number of animals used for this purpose. However, the results of these tests correlate more closely with lethal serum concentrations than with lethal doses. To address this issue, we have further evaluated the HPCT 1E3 model, which may be better able to emulate toxicokinetic factors that occur in vivo, due to the presence in these hepatocytoma cells of endogenous transmembrane carriers and a basal activity of xenobiotic metabolism. IC50 values produced by using the MTT test after a 48-hour incubation with 20 randomly selected MEIC substances, correlated better with human oral LD50 values than with LC50 data, supporting this hypothesis. As with other models, the toxicity of receptor-specific rather than cytotoxic substances, for example digoxin, was underpredicted. When digoxin was removed from the correlation analysis, the coefficient of determination (r(2)) improved to 0.81, and none of remaining chemicals were wrongly predicted by more than one order of magnitude. IC50 values obtained with HepG2 cells under similar conditions (MEIC Test No. 3, 24 hours, MTT) correlated with human LD50 data with a r(2) value of 0.55. A direct comparison of HPCT-1E3 and HepG2 cells further suggested that the differences between them may be due to transport processes. In conclusion, the HPCT-1E3 model may be valuable in improving the prediction of lethal doses, rather than lethal serum concentrations. PMID- 17850188 TI - In vitro tests for detecting chemicals affecting the embryo implantation process. The report and recommendations of ECVAM workshop 62 -- a strategic workshop of the EU ReProTect project. PMID- 17850189 TI - ECVAM's approach to intellectual property rights in the validation of alternative methods. AB - In this article, we discuss how intellectual property rights affect the validation of alternative methods at ECVAM. We point out recent cases and summarise relevant EU and OECD documents. Finally, we discuss guidelines for dealing with intellectual property rights during the validation of alternative methods at ECVAM. PMID- 17850190 TI - Prolonged in vivo gene silencing by electroporation-mediated plasmid delivery of small interfering RNA. AB - For the successful application of RNA interference in vivo, it is desired to achieve (local) delivery of small interfering RNAs (siRNAs) and long-term gene silencing. Nonviral electrodelivery is suitable to obtain local and prolonged expression of transgenes. By intramuscular electrodelivery of a plasmid in which two opposing human polymerase III promoters (H1 and U6) drive the expression of siRNA constructs that form functional double-stranded siRNAs, in combination with in vivo bioluminescence imaging, we were able to knock down exogenous delivered luciferase for at least 100 days in murine calf muscles. This effect was sequence specific, because scrambled siRNA had no effect. Moreover, we were able to demonstrate in vivo reduction of endogenous TLR4 expression for at least 1 week, using a similar vector expressing an siRNA for TLR4 in the muscle. In this study, we demonstrate that in vivo suppression of both endogenous (for at least 1 week) and introduced genes (>100 days) is feasible via plasmid-driven siRNA expression after electroporation-mediated intramuscular gene transfer. With this approach the short-term effect of oligonucleotides and the drawbacks of viral gene delivery, like immunological responses, could be circumvented. Therefore, this application of RNA interference is a useful tool with which to investigate gene function and might be promising as a therapeutic tool for locally acting diseases such as restenosis or tumors. PMID- 17850193 TI - International symposium: theory and neuroinformatics in research related to deep brain stimulation. PMID- 17850194 TI - Deep brain stimulation: indications and evidence. AB - Deep brain stimulation is a minimally invasive targeted neurosurgical intervention that enables structures deep in the brain to be stimulated electrically by an implanted pacemaker. It has become the treatment of choice for Parkinson's disease, refractory to, or complicated by, drug therapy. Its efficacy has been demonstrated robustly by randomized, controlled clinical trials, with multiple novel brain targets having been discovered in the last 20 years. Multifarious clinical indications for deep brain stimulation now exist, including dystonia and tremor in movement disorders; depression, obsessive-compulsive disorder and Tourette's syndrome in psychiatry; epilepsy, cluster headache and chronic pain, including pain from stroke, amputation, trigeminal neuralgia and multiple sclerosis. Current research argues for novel indications, including hypertension and orthostatic hypotension. The development, principles, indications and effectiveness of the technique are reviewed here. While deep brain stimulation is a standard and widely accepted treatment for Parkinson's disease after 20 years of experience, in chronic pain it remains restricted to a handful of experienced, specialist centers willing to publish outcomes despite its use for over 50 years. Reasons are reviewed and novel approaches to appraising clinical evidence in functional neurosurgery are suggested. PMID- 17850195 TI - Basal ganglia local field potentials: applications in the development of new deep brain stimulation devices for movement disorders. AB - The analysis of neural rhythms measured in local field potentials (LFPs) through deep brain stimulation (DBS) electrodes have provided a new insight into brain mechanisms of information processing. The application of novel methodological approaches for LFP analysis is of key importance to uncover the complexity of such mechanisms, thereby clarifying the relationship between the LFP code and patient's clinical state. Thanks to a new device for recording artifact-free LFPs during high-frequency stimulation, DBS-induced neural rhythms modulations and their nonlinear features can be analyzed and used in the development of a new, adaptive DBS approach: the frequency, strength and site of DBS could be controlled, in a closed-loop system, through LFP-based variables obtained through the application of different methodological approaches. PMID- 17850196 TI - Computational analysis of deep brain stimulation. AB - Chronic, high-frequency electrical stimulation of subcortical brain structures (deep brain stimulation [DBS]) is an effective clinical treatment for several medically refractory neurological disorders. However, the clinical successes of DBS are tempered by the limited understanding of the response of neurons to applied electric fields and scientific definition of the therapeutic mechanisms of DBS remains elusive. In addition, it is presently unclear which electrode designs and stimulation parameters are optimal for maximum therapeutic benefit and minimal side effects. Detailed computer modeling of DBS has recently emerged as a powerful technique to enhance our understanding of the effects of DBS and to create a virtual testing ground for new stimulation paradigms. This review summarizes the fundamentals of neurostimulation modeling and provides an overview of some of the scientific contributions of computer models to the field of DBS. We then provide a prospective view on the application of DBS-modeling tools to augment the clinical utility of DBS and to design the next generation of DBS technology. PMID- 17850197 TI - Modeling the current distribution across the depth electrode-brain interface in deep brain stimulation. AB - The mismatch between the extensive clinical use of deep brain stimulation (DBS), which is being used to treat an increasing number of neurological disorders, and the lack of understanding of the underlying mechanisms is confounded by the difficulty of measuring the spread of electric current in the brain in vivo. In this article we present a brief review of the recent computational models that simulate the electric current and field distribution in 3D space and, consequently, make estimations of the brain volume being modulated by therapeutic DBS. Such structural modeling work can be categorized into three main approaches: target-specific modeling, models of instrumentation and modeling the electrode brain interface. Comments are made for each of these approaches with emphasis on our electrode-brain interface modeling, since the stimulating current must travel across the electrode-brain interface in order to reach the surrounding brain tissue and modulate the pathological neural activity. For future modeling work, a combined approach needs to be taken to reveal the underlying mechanisms, and both structural and dynamic models need to be clinically validated to make reliable predictions about the therapeutic effect of DBS in order to assist clinical practice. PMID- 17850198 TI - Desynchronizing the abnormally synchronized neural activity in the subthalamic nucleus: a modeling study. AB - A mathematical model of a target area for deep brain stimulation was used to investigate the effects of electrical stimulation on pathologically synchronized clusters of neurons. In total, three newly developed stimulation techniques based on multisite coordinated reset and delayed feedback were tested and compared with a high-frequency stimulation method that is currently used as a standard stimulation protocol for deep brain stimulation. By modeling both excitatory and inhibitory actions of the electrical stimulation, we revealed the desynchronization impacts of the novel stimulation techniques. This contrasts with standard high-frequency stimulation, which failed to desynchronize the target population and whose inhibitory effects blocked all neuronal activity. We also explored the demand-controlled character of the proposed methods, and demonstrated that the amount of stimulation current required was considerably smaller than that for high-frequency stimulation. These novel stimulation methods appear to be superior to standard high-frequency stimulation techniques, and we propose the methods now be used for deep brain stimulation. PMID- 17850199 TI - Pathological cerebral oscillatory activity in Parkinson's disease: a critical review on methods, data and hypotheses. AB - Although well-known for more than a century, a sound pathophysiological mechanism for Parkinson's disease (PD) was lacking for a long time. The recent availability of electrophysiological techniques, such as magnetoencephalography, high resolution electroencephalography and intra- and post-operative recordings in PD patients undergoing deep brain stimulation, allowed new approaches to record neuronal activity. Furthermore, the new application of signal analysis tools, such as the fast Fourier transformation, coherence, phase shifts, as well as causality measures, gave tremendous new insights into mechanisms of frequency dependent oscillatory coupling. This review highlights these new analysis approaches, reviews the noninvasive magnetoencephalography, electroencephalography and intra- and post-operative data on PD patients, and summarizes the modern hypothesis that PD results from pathological oscillatory synchronization in the human sensorimotor system. PMID- 17850200 TI - Neuroinformatics and modeling of the basal ganglia: bridging pharmacology and physiology. AB - The subthalamic nucleus (STN) is the primary target for the chronic deep brain stimulation treatment of Parkinson's disease. STN neurons exhibit a variety of characteristic properties that may play a key role in the overall population response to deep brain stimulation. Neuroinformatics techniques, in particular computational modeling, provide a method of bringing together pharmacological phenomena, such as the loss of dopamine, with electrophysiological characteristics. Developing accurate models of STN neurons plays an important part in the process of uncovering the link between the changes in STN pharmacology, physiology and synaptic input that occurs with Parkinson's disease and the effectiveness of treatments targeting the STN. We review a general procedure for developing computational models and present a model of STN neurons that reveals important membrane channel interactions. In particular, changes in these channel interactions under parkinsonian conditions may underlie changes in characteristic physiology, critical in determining the mechanisms of deep brain stimulation. PMID- 17850201 TI - Vaginal mesh for incontinence and/or prolapse: caution required! PMID- 17850203 TI - AIR Inhaled Insulin System: a novel insulin-delivery system for patients with diabetes. AB - Over time, most patients with Type 2 diabetes require insulin-replacement therapy to attain and sustain the increasingly stringent glycemic goals. Initiation of subcutaneous insulin may be delayed due to patient or provider resistance. This delay may increase the risk of complications from long-term hyperglycemia. The development of inhaled insulin-delivery systems has been pursued to facilitate earlier initiation and optimization of insulin therapy to achieve better treatment outcomes. The AIR((R)) Inhaled Insulin System utilizes relatively large, low-density particles, allowing efficient drug delivery to the deep lung from a simple inhaler. In clinical studies it has provided similar postprandial glycemic control compared with subcutaneously injected, short-acting insulin, and was preferred by more patients. The purpose of this article is to describe the AIR Inhaled Insulin System, provide an overview of other insulin-delivery systems and discuss future strategies for the treatment of diabetes. PMID- 17850204 TI - Percutaneous tibial nerve stimulation: the Urgent PC device. AB - Lower urinary tract disorders, with its main representative the overactive bladder, are an increasing problem that impact patients' quality of life tremendously. Neuromodulative treatment may fill the gap between conservative measures and invasive surgery. Percutaneous tibial nerve stimulation (Urgent PC) is a neuromodulation technique that is minimally invasive and easy to perform. Stimulation is carried out in 12 weekly sessions of 30 min each, through a percutaneously placed needle cephalad to the medial malleolus. Success can be obtained in approximately two-thirds of patients, but the therapy has the disadvantage of the necessity of maintenance therapy. The development of a small implantable device may be the future next step in the evolution of the technique. PMID- 17850205 TI - Allergan's silicone gel breast implants. AB - In the USA, women seeking breast implants for augmentation, revision or reconstruction can choose between saline-filled devices and round, silicone gel filled devices. Form-stable, highly cohesive silicone gel-filled breast implants are marketed in other countries and are currently under review by the US FDA. Allergan has conducted clinical studies to investigate the safety and effectiveness of its round and anatomical (Style 410) devices for US marketing approval. The most frequently reported complications were reoperation, implant removal with replacement, implant malposition and capsular contracture. The FDA approved the round devices in 2006. The weight of the scientific literature suggests that silicone gel-filled breast implants do not increase a patient's risk of cancer, autoimmune disease, reproductive effects or suicide. As differently shaped, cohesive breast implants continue to be introduced, breast implant surgery will become more customized to the patient's biological conditions and desires. PMID- 17850206 TI - From scrawny to brawny: the quest for neomusculogenesis; smart surfaces and scaffolds for muscle tissue engineering. AB - The successful generation of functional muscle tissues requires both an in-depth knowledge of muscle tissue physiology and advanced engineering practices. The inherent contractile functionality of muscle is a result of its high-level cellular and matrix organization over a multitude of length scales. While there have been many attempts to produce artificial muscle, a method to fabricate a highly organized construct, comprised of multiple cell types and capable of delivering contractile strengths similar to that of native smooth, skeletal or cardiac muscle has remained elusive. This is largely due to a lack of control over phenotype and spatial organization of cells. This paper covers state-of-the art approaches to generating both 2D and 3D substrates that provide some form of higher level organization or multiple biochemical, mechanical or electrical cues to cells in order to successfully manipulate their behavior, in a manner that is conducive to the production of contractile muscle tissue. These so-called 'smart surfaces' and 'smart scaffolds' represent vital steps towards surface-engineered substrates for the engineering of muscle tissues, showing confidently that cellular behavior can be effectively and reproducibly manipulated through the design of the physical, chemical and electrical properties of the substrates on which cells are grown. However, many challenges remain to be overcome prior to reaching the ultimate goal of fully functional 3D vascularized engineered muscle. PMID- 17850207 TI - Biomaterials for tissue reconstruction and bone substitution of the ear, nose and throat, face and neck. AB - The role of biomaterials has become more important in the last 30 years in otorhinolaryngology. Legal directives for their use and, more importantly, indications have been specified. Biomaterials are medical devices, designed for tissue substitution or reconstruction. Approval labeling is issued in the form of European Community certification and postmarketing medical device safety in Europe - completely independent from the US FDA's certification. The indications for biomaterials are generally similar to those of autografts. Their main advantage is that they limit the morbidity caused by autograft harvesting. The benefits are aesthetic, functional or both. The main indications are in otology, sinus surgery, cranio-maxillo-facial traumatology, osteosynthesis and orthognatic surgery, skeletal augmentation and anti-aging surgery, facial prosthetic rehabilitation and laryngology. The research fields are extremely varied (e.g., increased therapeutic properties, drug-delivery systems or tissue engineering). Increasingly, biomaterials are implanted and the surgical success of their use is dependent upon strict legal labeling and well-defined indications. PMID- 17850208 TI - Stents in the GI tract. AB - The application of stents in the GI tract has expanded tremendously. Stent placement is the most frequently used treatment modality for palliating dysphagia from esophageal or gastric cardia cancer. Newly designed esophageal stents, including the Polyflex stent and the Niti-S double stent, have been introduced to reduce recurrent dysphagia owing to migration or nontumoral or tumor overgrowth. Stents are also the treatment of choice for esophagorespiratory fistulas, for proximal malignant lesions near the upper esophageal sphincter, for recurrent carcinoma after esophagectomy or gastrectomy and for sealing traumatic or iatrogenic nonmalignant ruptures, such as Boerhaave's syndrome and leakages following surgery. Stents in the latter patient group should be removed within 4 8 weeks after placement to prevent the formation of granulation tissue or hyperplasia at the stent ends. For gastric outlet obstruction, many case series have been published. Only two, small, randomized controlled trials have compared stent placement with gastrojejunostomy to date, and a large, randomized trial is currently being conducted in The Netherlands. Obstructive jaundice caused by a malignancy in the common bile duct can be treated effectively with plastic or metal stent placement. However, a prognostic score needs to be developed that guides a treatment decision towards using either of these stents. Finally, colonic stents are applied successfully for acute malignant obstruction as a 'bridge to surgery' in patients with tumors that are deemed to be resectable, or as a palliative treatment for patients with locally advanced or metastatic disease. PMID- 17850209 TI - Structure and function of the cell surface (tethered) mucins. AB - Cell surface mucins are large transmembrane glycoproteins involved in diverse functions ranging from shielding the airway epithelium against pathogenic infection to regulating cellular signaling and transcription. Although hampered by the relatively recent characterization of cell surface mucins and the difficulties inherent in working with molecules of their size, numerous studies have placed the tethered mucins in the thick of normal and diseased lung physiology. This review focuses on the three best-characterized cell surface mucins expressed in the respiratory tract: MUC1, MUC4, and MUC16. PMID- 17850210 TI - Hypoxia-induced signaling in the cardiovascular system. AB - Low oxygen (O2) levels are a naturally occurring feature of embryonic development, adult physiology, and diseases such as those of the cardiovascular system. Although many responses to O2 deprivation are mediated by hypoxia inducible factors (HIFs), researchers are finding a growing number of HIF independent pathways that promote O2 conformance and hypoxia tolerance. Here, we describe HIF-independent responses and how they impact cardiovascular tissue homeostasis. PMID- 17850211 TI - Mechanisms and regulation of epithelial Ca2+ absorption in health and disease. AB - Ca2+ is essential for numerous physiological functions in our bodies. Therefore, its homeostasis is finely maintained through the coordination of intestinal absorption, renal reabsorption, and bone resorption. The Ca2+-selective epithelial channels TRPV5 and TRPV6 have been identified, and their physiological roles have been revealed: TRPV5 is important in final renal Ca2+ reabsorption, and TRPV6 has a key role in intestinal Ca2+ absorption. The TRPV5 knockout mice exhibit renal leak hypercalciuria and accordingly upregulate their intestinal TRPV6 expression to compensate for their negative Ca2+ balance. In contrast, despite their severe negative Ca2+ balance, TRPV6-null mice do not display any compensatory mechanism, thus resulting in secondary hyperparathyroidism. These results indicate that the genes for TRPV5 and TRPV6 are differentially regulated in human diseases associated with disturbed Ca2+ balance such as hypercalciuria, osteoporosis, and vitamin D-resistant rickets. PMID- 17850212 TI - Polarized calcium signaling in exocrine gland cells. AB - Cytosolic Ca2+ signals are crucial for the control of fluid and enzyme secretion from exocrine glands. The highly polarized exocrine acinar cells have evolved sophisticated and complex Ca2+ signaling mechanisms that exercise precise control of the secretory events occurring across the apical plasma membrane bordering the gland lumen. Ca2+ stores in the endoplasmic reticulum, the secretory granules, the lysosomes, and the endosomes all play important roles in the generation of the local apical Ca2+ spikes that switch on Cl(-) channels in the apical plasma membrane as well as exocytotic export of enzymes. The mitochondria are crucial not only for ATP generation but also for the physiologically important subcellular compartmentalization of the cytosolic Ca2+ signals. PMID- 17850213 TI - Structure and function of the polymeric mucins in airways mucus. AB - The airways mucus gel performs a critical function in defending the respiratory tract against pathogenic and environmental challenges. In normal physiology, the secreted mucins, in particular the polymeric mucins MUC5AC and MUC5B, provide the organizing framework of the airways mucus gel and are major contributors to its rheological properties. However, overproduction of mucins is an important factor in the morbidity and mortality of chronic airways disease (e.g., asthma, cystic fibrosis, and chronic obstructive pulmonary disease). The roles of these enormous, multifunctional, O-linked glycoproteins in health and disease are discussed. PMID- 17850215 TI - Lysosomal leakage and lack of adaptation of hepatoprotective enzyme contribute to enhanced susceptibility to ethanol-induced liver injury in female rats. AB - BACKGROUND: Women exhibit greater liver damage than men after chronic alcohol consumption. Similar findings are reported in animal models. Here, we determined whether differential liver injury occurred in male and female rats after feeding these animals liquid diets containing either ethanol or isocaloric dextrose with fish oil as the sole source of lipid. METHODS: Control and ethanol liquid diets containing fish oil were pair-fed to male and female rats for 8 weeks. Liver damage was evaluated by triglyceride accumulation, lipid peroxide formation, serum transaminases, histological evaluation, and the activities of selected lysosomal and hepatoprotective enzymes. RESULTS: Fatty liver was detected after ethanol feeding in both genders, but in female rats, triglyceride levels were 60% higher, lipid peroxides were 2-fold higher, and inflammatory cells were more evident than in males. A 2-fold elevation of cathepsin B in hepatic cytosol fractions, indicating lysosomal leakage, was detected in ethanol-fed female rats but no such elevation was observed in males. The basal activity of the hepatoprotective enzyme, betaine-homocysteine methyltransferase was 4-fold higher in livers of control male rats than females, and the enzyme activity was further elevated in ethanol-fed male rats but not in females. CONCLUSIONS: Thus, female rats given ethanol in a diet containing fish oil exhibited more severe liver damage than males. We propose that this difference results, in part, from a greater tendency by females to accumulate hepatic fat, thereby enhancing the potential for oxidative stress, which in turn leads to hepatic inflammation. In addition, our findings indicate that female rats have a higher susceptibility to liver damage because of a reduced capacity for hepatoprotection. PMID- 17850214 TI - The selectivity of protein kinase inhibitors: a further update. AB - The specificities of 65 compounds reported to be relatively specific inhibitors of protein kinases have been profiled against a panel of 70-80 protein kinases. On the basis of this information, the effects of compounds that we have studied in cells and other data in the literature, we recommend the use of the following small-molecule inhibitors: SB 203580/SB202190 and BIRB 0796 to be used in parallel to assess the physiological roles of p38 MAPK (mitogen-activated protein kinase) isoforms, PI-103 and wortmannin to be used in parallel to inhibit phosphatidylinositol (phosphoinositide) 3-kinases, PP1 or PP2 to be used in parallel with Src-I1 (Src inhibitor-1) to inhibit Src family members; PD 184352 or PD 0325901 to inhibit MKK1 (MAPK kinase-1) or MKK1 plus MKK5, Akt-I-1/2 to inhibit the activation of PKB (protein kinase B/Akt), rapamycin to inhibit TORC1 [mTOR (mammalian target of rapamycin)-raptor (regulatory associated protein of mTOR) complex], CT 99021 to inhibit GSK3 (glycogen synthase kinase 3), BI-D1870 and SL0101 or FMK (fluoromethylketone) to be used in parallel to inhibit RSK (ribosomal S6 kinase), D4476 to inhibit CK1 (casein kinase 1), VX680 to inhibit Aurora kinases, and roscovitine as a pan-CDK (cyclin-dependent kinase) inhibitor. We have also identified harmine as a potent and specific inhibitor of DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A) in vitro. The results have further emphasized the need for considerable caution in using small molecule inhibitors of protein kinases to assess the physiological roles of these enzymes. Despite being used widely, many of the compounds that we analysed were too non-specific for useful conclusions to be made, other than to exclude the involvement of particular protein kinases in cellular processes. PMID- 17850216 TI - S-adenosylmethionine attenuates oxidative liver injury in micropigs fed ethanol with a folate-deficient diet. AB - BACKGROUND: To demonstrate a causative role for abnormal methionine metabolism in the pathogenesis of alcoholic steatohepatitis (ASH), we measured the preventive effects of supplementing folate deficient and ethanol containing diets in the micropig with S-adenosylmethionine (SAM), a metabolite that regulates methionine metabolism. METHODS: Yucatan micropigs were fed folate-deficient diets as control, with ethanol at 40% of kcal, or with ethanol supplemented with SAM at 0.4 g/1000 kcal for 14 weeks. Histopathology, markers of liver injury, and regulatory enzymes were measured in terminal liver samples. RESULTS: Among the ethanol group, livers showed hepatocellular necrosis together with increased levels of S-adenosylhomocysteine (SAH) and reduced levels of SAM and its ratio to SAH and glutathione (GSH), together with increased malondialdehyde plus hydroxynonenol (MDA + HNE) and nitrotyrosine (NT), transcripts and protein levels of cytochrome P4502E1 (CYP2E1), activity of NADPH oxidase, and activity and protein levels of inducible nitric oxide (iNOS). These findings were attenuated partially or completely to control levels by SAM supplementation of the ethanol diet. CONCLUSIONS: The present results indicate that SAM supplementation attenuates ethanol induced liver injury through its effects on the expressions and activities of oxidative stress pathways, and are consistent with the concept that the pathogenesis of oxidative liver injury is regulated in part through altered hepatic methionine metabolism. PMID- 17850217 TI - Orexigenic peptides and alcohol intake: differential effects of orexin, galanin, and ghrelin. AB - BACKGROUND: The question is which hypothalamic systems for food intake might play a role in ethanol intake and contribute to alcohol abuse. The peptide orexin was found to exhibit similar properties to galanin in its relation to dietary fat and may therefore be similar to galanin in having a stimulatory effect on alcohol intake. METHODS: Rats were trained to drink 10% ethanol, implanted with brain cannulas, and then injected in the paraventricular nucleus (PVN), lateral hypothalamus (LH), or nucleus accumbens (NAc) with galanin, orexin-A, and for comparison, ghrelin. Ethanol, food, and water intake were measured at 1, 2, and 4 hours postinjection. RESULTS: In the PVN, both orexin and galanin significantly increased ethanol intake, whereas ghrelin increased food intake. In the LH, orexin again induced ethanol intake, while ghrelin increased eating. In the NAc, orexin failed to influence ethanol intake but did stimulate food intake. CONCLUSIONS: In ethanol-drinking rats, injection of orexin or galanin into the appropriate locus in the hypothalamus induced significant ethanol intake instead of food intake. Ghrelin, as a positive control, failed to influence ethanol intake at the same hypothalamic sites. In the NAc, as an anatomical control, orexin augmented eating but not ethanol intake. Thus orexin and galanin in the hypothalamus selectively stimulated ethanol intake at sites where other studies have shown that both ethanol and fat increase expression of the endogenous peptides. Thus, a neural circuit that evolved with the capability to augment food intake is apparently co-opted by ethanol and may serve as a potential positive feedback circuit for alcohol abuse. PMID- 17850219 TI - Mouse lines selected for alcohol consumption differ on certain measures of impulsivity. AB - BACKGROUND: Alcoholics and heavy drinkers score higher on measures of impulsivity than nonalcoholics and light drinkers. This may be due to factors that predate drug exposure (e.g. genetics) or to neuroadaptations associated with exposure to alcohol. The aim of this study was to examine the role of genetics by comparing impulsivity in short-term selected lines of mice bred to voluntarily drink either high (STDRHI2) or low (STDRLO2) amounts of 10% ethanol. METHODS: Independent sets of mice completed 2 experiments designed to measure impulsivity. Using the adjusting amount procedure, we examined preference for smaller, sooner rewards over larger but delayed rewards (delay discounting). This task determines the amount of immediate sucrose equivalent to the discounted value of a 20 microl sucrose reward given following a specific delay (0, 2, 4, 8, or 12 seconds). Using a Go/No-go task, we examined the ability of mice to inhibit nose-poking in response to specific cues. These tasks are commonly used to assess different aspects of impulsive behavior, and provide measures that are not highly correlated. RESULTS: No significant differences were found between STDRHI2 and STDRLO2 mice in delay discounting. In the Go/No-go task, STDRHI2 mice made more responses during the pre-cue period without committing more false alarms, compared with STDRLO2 mice. CONCLUSIONS: The results suggest that short-term selective breeding for high relative alcohol consumption may also select for animals that have impaired response inhibition. PMID- 17850220 TI - Decreased plasma brain-derived neurotrophic factor levels in patients with alcohol dependence. AB - BACKGROUND: Many reports have suggested possible relationships between brain derived neurotrophic factor (BDNF) and alcohol dependence. A protective effect of BDNF against ethanol-induced cell damage has been suggested, and this effect may contribute to the development or maintenance of alcohol dependence. This study was carried out in order to verify the significance of BDNF in alcohol dependence. METHODS: Peripheral BDNF levels were measured in alcohol-dependent patients and control subjects using an enzyme-linked immunosorbent assay. A physician's interview and standardized questionnaire were used to obtain information regarding each patient's history of alcohol consumption. RESULTS: The mean BDNF level was lower in the alcohol dependence group (389.5 +/- 501.7 pg/ml) than in the normal controls (822.5 +/- 420.7 pg/ml) by analysis of covariance (ANCOVA) (F = 25.79, p < 0.01). The mean BDNF level was lower in the alcohol dependent patients with a positive family history of alcohol dependence (247.6 +/ 289.2 pg/ml) than in those with a negative family history of alcohol dependence (583.9 +/- 652.8 pg/ml) by ANCOVA (F = 6.51, p = 0.01). The BDNF levels did not correlate significantly with any of the variables analyzed in this study, including Beck depression inventory, state and trait anxiety inventory (STAI-S and T), and various drinking behaviors. CONCLUSIONS: Changes in the levels of BDNF might play a role in the pathophysiology and inheritance of alcohol dependence. PMID- 17850218 TI - The impact of gonadectomy and adrenalectomy on acute withdrawal severity in male and female C57BL/6J and DBA/2J mice following a single high dose of ethanol. AB - BACKGROUND: Steroid hormones can influence neuronal excitability and subsequent seizure susceptibility through genomic and nongenomic mechanisms. For example, there are proconvulsant steroids such as estradiol and corticosterone and anticonvulsant steroids such as testosterone, progesterone, and their GABAergic metabolites. Recent findings indicated that a single, acute administration of ethanol increased levels of GABAergic steroids and that the source of this increase was peripheral organs such as the adrenals and gonads. Thus, the purpose of the present study was to determine the impact of removal of the adrenals and/or gonads on withdrawal severity following a single high dose of ethanol in 2 genotypes that differ in ethanol withdrawal severity. METHOD: Male and female C57BL/6J (B6) and DBA/2J (D2) mice were either left intact (SHAM), adrenalectomized (ADX), gonadectomized (GDX), or underwent ADX/GDX surgery. Seven days following surgery, baseline handling-induced convulsions (HICs) were measured prior to administration of a 4 g/kg dose of ethanol. HICs were assessed following the ethanol injection, then hourly for 12 hours and at 24 hours. A separate group of mice were used to measure the impact of surgical status on ethanol metabolism at 30, 60, 120, and 240 minutes after a single 4 g/kg dose of ethanol. RESULTS: ADX and ADX/GDX treatments in male B6 and D2 mice increased ethanol withdrawal severity following a single dose of ethanol, measured by area under the withdrawal curve and peak HIC scores. Acute ethanol withdrawal also was increased in female D2 mice that had undergone ADX/GDX. In contrast, surgical status did not alter ethanol withdrawal severity in female B6 mice. Surgical status had only minor effects on ethanol metabolism. CONCLUSIONS: Removal of peripherally derived steroids with anticonvulsant properties significantly increased HIC scores during acute ethanol withdrawal following a single dose of ethanol in male and female D2 mice and in male B6 mice. These increases were not due to changes in ethanol metabolism. PMID- 17850221 TI - Varieties of impulsivity in males with alcohol dependence: the role of Cluster-B personality disorder. AB - BACKGROUND/RATIONALE: Impulsivity has been associated with alcohol dependence, but impulsivity in alcohol-dependent subjects with a Cluster-B personality disorder (PD) has not been well characterized. Using a variety of laboratory measures of impulsivity, we assessed whether alcohol-dependent patients (ADP) with borderline personality disorder (BPD) exhibited the same pattern of behavioral impulsivity than ADP with antisocial personality disorder (AntPD). Also, differences between ADP without PDs and healthy controls were assessed. METHODS: A cross-sectional patient survey with a community comparison group. Diagnoses were made using the Structured Interview for DSM-IV. Sustained attention and rapid-response impulsivity were assessed using the continuous performance test. Inhibitory control was measured by the stop-signal task. Ability to delay reward task was assessed using differential reinforcement for low-rate responding (DRLR). A final sample of 247 males with alcohol-dependence recruited from 2 alcoholism treatment centers was compared with a matched nonsubstance-abusing comparison group (n = 96). RESULTS: Alcohol-dependent patients with BPD made more omission errors than ADP with AntPD, but individuals with AntPD exhibited the poorest efficiency in DRLR. ADPs with a Cluster-B PD displayed more impairment across all behavioral measures than ADP without PD and than controls. In contrast, with respect to controls ADP without a Cluster-B PD showed more impairment only in DRLR. CONCLUSIONS: Our findings support the suggestion of 2 paradigms in alcohol dependence. The first, based on inability to delay gratification, might be a vulnerability marker for alcohol dependence. The second was related to inhibitory control and might be specific for AntPD and BPDs. PMID- 17850222 TI - Lack of association of alcohol dependence and habitual smoking with catechol-O methyltransferase. AB - OBJECTIVE: To test whether variation in the gene encoding the enzyme catechol-O methyltransferase (COMT), which catalyzes the breakdown of dopamine and other catecholamine neurotransmitters, is associated with the risk for alcohol dependence and habitual smoking. METHODS: Single nucleotide polymophisms (SNPs) were genotyped in a sample of 219 multiplex alcohol-dependent families of European American descent from the Collaborative Study on the Genetics of Alcoholism (COGA). Family-based tests of association were performed to evaluate the evidence of association between the 18 SNPs distributed throughout COMT, including the functional Val158Met polymorphism, and the phenotypes of alcohol dependence, early onset alcohol dependence, habitual smoking, and comorbid alcohol dependence and habitual smoking. RESULTS: No significant, consistent evidence of association was found with alcohol dependence, early onset alcohol dependence, habitual smoking or the comorbid phenotype. There was no evidence that the functional Val158Met polymorphism, previously reported to be associated with these phenotypes, was associated with any of them. CONCLUSION: Despite the substantial size of this study, we did not find evidence to support an association between alcohol dependence or habitual smoking and variation in COMT. PMID- 17850223 TI - Intact preference conditioning in acute intoxication despite deficient declarative knowledge and working memory. AB - BACKGROUND: The impact of alcohol on implicit, emotional learning is not well understood, partly because family history, drug use, and task demands influence these processes. The conditioned pattern preference (CPP) task provides a more ecologically valid means to investigate implicit cognition in the lab because it has low demand awareness and relies on learning to associate nonverbal cues with reward. METHODS: This study examined the effects of acute alcohol intoxication on implicit learning using the CPP task in 83 intoxicated and 69 sober young adults. Information on individual drug use, family history, impulsivity, and alcohol expectancies was also collected. RESULTS: Alcohol intoxication affected explicit, but not implicit learning on the CPP task. In addition, participants who reported a positive family history of addiction (FH+) or individual recreational drug use did not exhibit a preference for cues previously paired with reward. CONCLUSIONS: Preference formation on the CPP task recruits motivational neurocircuitry, an effect that is unaltered by alcohol. Group differences in implicit emotional learning on this task may represent neurocognitive differences in individuals at risk for addiction. PMID- 17850224 TI - Thiopental and halothane dose-sparing effects of magnesium sulphate in dogs. AB - OBJECTIVE: To evaluate the effect of pre- and intraoperatively administered magnesium sulphate (MgSO(4)) on the induction dose of thiopental and of halothane for maintenance of anaesthesia in dogs undergoing ovariohysterectomy (OHE). STUDY DESIGN: Prospective, double-blind, randomized, placebo-controlled study. ANIMALS: Forty-six healthy, ASA physical status 1 dogs, scheduled for elective OHE. METHODS: The dogs were randomly assigned to receive a bolus of 50 mg kg(-1) MgSO(4) intravenously (IV), just before induction of anaesthesia, followed by a constant rate infusion (CRI) of 12 mg kg(-1) hour(-1) MgSO(4) intraoperatively (group Mg, n = 27) or a placebo bolus and CRI of 0.9% sodium chloride (NaCl) (group C, n = 19), approximately 30 minutes after premedication with acepromazine (0.05 mg kg(-1), intramuscularly, IM) and carprofen (4 mg kg(-1), subcutaneously, SC). Anaesthesia was induced with thiopental administered to effect and maintained with halothane in oxygen. End-tidal halothane (ET(hal)) was adjusted to achieve adequate depth of anaesthesia. Blood samples were obtained pre- and postoperatively for measurement of total serum magnesium concentration. RESULTS: The mean dose of thiopental was statistically lower (p < 0.0005) and the mean standardized ET(hal) concentration and end-tidal carbon dioxide partial pressure (Pe'CO(2)) areas under the curve were statistically smaller (p < 0.0005 and 0.014 respectively) in group Mg. Postoperatively the mean total serum magnesium concentration was statistically higher than the preoperative value (p < 0.0005) in group Mg, but not in group C. Nausea, associated with the MgSO(4) bolus injection, was observed in six dogs in group Mg, two of which vomited prior to induction of anaesthesia. CONCLUSIONS AND CLINICAL RELEVANCE: Magnesium sulphate administration reduced the induction dose of thiopental and ET(hal) concentration for maintenance of anaesthesia in dogs undergoing OHE. Observed side effects were nausea and vomiting. PMID- 17850225 TI - Comparison of peripheral and core temperatures in anaesthetized hypovolaemic sheep. AB - OBJECTIVE: To compare rectal (C(R) degrees ), coronary band (P(CB) degrees ) and ear base (P(E) degrees ) temperatures with pulmonary arterial temperature (C(PA) degrees ), and to investigate the relationship between core-peripheral temperature difference ([C - P]t degrees ) and cardiac output (Qt) in an acute ovine trauma model (PIL 60/9064). STUDY DESIGN: Observational study. ANIMALS: Thirteen mixed-breed male sheep, body mass (mean +/- SD) 45.50 +/- 4.21 kg, aged approximately 1 year. MATERIALS AND METHODS: Anaesthesia was induced with intravenous etomidate 0.5 mg kg(-1) and midazolam 0.5 mg kg(-1) and following endotracheal intubation maintained with halothane in a 2:1 N(2)O:O(2) mixture. The lungs were mechanically ventilated to maintain normocapnia. Core temperature was measured using a pulmonary arterial thermistor. Rectal temperature and peripheral temperatures at the thoracic limb coronary band and ear base were recorded using thermistor probes with a multi-channel recorder. Cardiac output was measured by continuous thermodilution. Recordings were taken hourly over a 24 hour period. After baseline data collection, hypovolaemia was induced by haemorrhage from bilateral femoral fractures. The development of hypovolaemic shock was confirmed by falling Qt, central venous pressure, mean arterial pressure and urine output. Resuscitation was attempted using intravenous fluids, inotropes and vasoconstrictors. Nine sheep received lumbosacral extradural bupivacaine. RESULTS: The rectal temperature correlated closely with pulmonary arterial temperature in all sheep (r(c) = 0.924). There was no consistent statistically significant relationship between Qt and [C - P]t degrees . CONCLUSIONS AND CLINICAL RELEVANCE: Rectal temperature accurately reflected core temperature in anaesthetized sheep but [C - P]t degrees was unrelated to Qt, under the conditions described in this study. PMID- 17850226 TI - The isoflurane-sparing and clinical effects of a constant rate infusion of remifentanil in dogs. AB - OBJECTIVE: To evaluate the isoflurane-sparing and clinical effects of two constant rate infusions of remifentanil in healthy dogs undergoing orthopaedic surgery. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: Forty-one American Society of Anesthesiologists I-II client-owned dogs (age, 7 months-9 years; body mass 11-59 kg). METHODS: Dogs were randomly assigned to one of three groups and received either: intramuscular (IM) meperidine 2 mg kg(-1) every 2 hours throughout surgery (control group (C); n = 13); remifentanil infused intravenously (IV) at 0.1 microg kg(-1) minute(-1) (low remifentanil group (L); n = 14) or remifentanil infused at 0.25 microg kg(-1) minute(-1) IV (high remifentanil group (H); n = 14). Anaesthesia was induced with thiopental administered to effect and maintained using isoflurane in 100% oxygen. During controlled ventilation when the end-tidal CO(2) was maintained between 4.65 and 5.98 kPa [35-45 mmHg], the end-tidal isoflurane concentration (e'iso%), mean arterial blood pressure (MAP) and heart rate (HR) were measured every 5 minutes. Bradycardia (HR < 40 minute(-1) lasting >5 minutes) was corrected with 0.01 mg kg(-1) IV glycopyrrolate. Data were analysed using the Kruskal-Wallis test with a post-hoc Mann-Whitney U-test and Bonferroni correction. Statistical significance was accepted at < or = 0.05. Data are expressed as mean +/- standard deviation. RESULTS: The e'iso% was reduced in a dose-dependent manner by remifentanil. In C, e'iso% was 1.28 +/-0.13 and was significantly different from L (0.78 +/- 0.17, p < 0.001) and H (0.65 +/- 0.16, p < 0.001). HR was significantly different between groups (p < 0.001). There were no significant differences in MAP between groups. Glycopyrrolate was required in two, three and six dogs in the C, L and H groups respectively. CONCLUSIONS: Remifentanil infusion reduced the isoflurane concentration required for surgical anaesthesia during orthopaedic surgery. CLINICAL RELEVANCE: Remifentanil infusions may be a useful additive to isoflurane anaesthesia in healthy dogs. PMID- 17850227 TI - Effects of propofol on ultrasonic indicators of haemodynamic function in rabbits. AB - OBJECTIVE: To evaluate the cardiovascular effects of intravenous propofol in rabbits. STUDY DESIGN: Randomized, prospective, experimental study. ANIMALS: Thirty-one female New Zealand White rabbits. METHODS: Rabbits were allocated to one of two groups [propofol (P) or conscious (C)]. In C (n = 16) vascular dimensions were measured using ultrasound of the left common carotid artery (ACC) and the abdominal aorta (AA). Group P (n = 15) received propofol 4.0-8.0 mg kg( 1) intravenously (IV). Anaesthesia was maintained with propofol at 1.2-1.3 mg kg( 1) minute(-1). Subsequently, three propofol injections (8 mg kg(-1)) were given. Before and for 10 minutes after each injection the following vascular and haemodynamic variables were recorded (a) at the ACC after the first injection; and (b) at the AA after the second injection: vessel diameter [D, (mm)], peak systolic, minimum diastolic, end-diastolic and average blood flow velocities [psBFV, mdBFV, edBFV, Vave (cm second(-1))], average volumetric flow [VFave (mL s(-1))], resistance index (RI) and pulsatility index (PI) mean arterial pressure (MAP), heart rate (HR), arterial oxygen saturation (SpO(2)) and end-tidal CO(2) (Pe'CO(2)). Echocardiography was performed after the third propofol bolus injection to investigate changes in cardiac parameters [fractional shortening, FS (%)]. RESULTS: Intravenous propofol injections caused a significant decrease in vessel diameter, volumetric flow and edBFV, and significant increases in psBFV, RI and PI. Baseline levels for vessel diameter and psBFV were restored 6-8 minutes after injection. Propofol injection decreased FS significantly by 7 minutes after injection while MAP and HR were significantly reduced for 4 minutes. CONCLUSION AND CLINICAL RELEVANCE: Injections of propofol (8 mg kg(-1)) produced an immediate, transient decrease in vascular diameters, a significant decrease in ventricular performance and an increase in peripheral vascular resistance (ACC and AA). Propofol should probably not be or only carefully used in rabbits with ventricular dysfunction. PMID- 17850228 TI - Comparison between analgesic effects of buprenorphine, carprofen, and buprenorphine with carprofen for canine ovariohysterectomy. AB - OBJECTIVE: To compare the analgesic effects of buprenorphine, carprofen, and their combination in dogs undergoing ovariohysterectomy. STUDY DESIGN: Prospective, randomized blinded clinical study. ANIMALS: 60 dogs. METHODS: Treatments were buprenorphine 0.02 mg kg(-1), intramuscularly (IM) (group B); carprofen 4 mg kg(-1), subcutaneously (SC) (group C); or a combination of both (group CB). Anesthesia was induced with propofol and maintained with isoflurane. A Dynamic Interactive Visual Analog Scale (DIVAS, 0-100 mm) and the Glasgow Composite Pain Scale (GCMPS, 0-24) were used to evaluate comfort and sedation at baseline, 2, 4, 6, and 24 hours after extubation. Rescue analgesia was provided with buprenorphine (0.02 mg kg(-1)). Wound swelling measurements (WM) and a visual inflammation score (VIS) of the incision were made after surgery and 2, 4, 6, and 24 hours later. p < 0.05 was considered significant. RESULTS: Group C required more propofol (5.0 +/- 1.4 mg kg(-1)) compared with B (3.3 +/- 1.1 mg kg(-1)) and CB (3.2 +/- 0.7 mg kg(-1)); respectively, p = 0.0002 and 0.0001. Rescue analgesia was required in nine dogs. B had a higher GCMPS and DIVAS III score at 6 hours (2.6 +/- 2.5) and (23 +/- 22.5 mm) compared with C (1.0 +/- 1.3, 6 +/- 7.3 mm) and CB (1.5 +/- 1.4, 8 +/- 10.7 mm); respectively, p = 0.02 and 0.006. Group C had a lower sedation score at 2 hours (43 +/- 23.6 mm) compared with B (68 +/- 32.1 mm) and BC (69 +/- 22.1 mm); respectively, p = 0.03 and 0.004. Group B had a higher WM score at 2 hours (3 +/- 0.8 mm) compared with C (2 +/- 0.6 mm) p = 0.01 and at 6 hours (3 +/- 1 mm) compared with C (2 +/- 0.8 mm) and CB (2 +/- 0.8 mm); respectively, p = 0.01 and 0.008. VIS was not different between groups. CONCLUSION AND CLINICAL RELEVANCE: All treatments provided satisfactory analgesia for the first 6 hours and at 24 hours. C and CB pain score and WS were superior to B at 6 hours. No superior analgesic effect was noted when the drugs were combined. PMID- 17850229 TI - Regulation of Arf activation: the Sec7 family of guanine nucleotide exchange factors. AB - The ADP ribosylation factors (Arfs) are a family of small, ubiquitously expressed and evolutionarily conserved guanosine triphosphatases that are key regulators of vesicular transport in eukaryotic cells (D'Souza-Schorey C, Chavrier P. ARF proteins: roles in membrane traffic and beyond. Nat Rev Mol Cell Biol 2006;7:347 358). Although Arfs are best known for their role in the nucleation of coat protein assembly at a variety of intracellular locations, it is increasingly apparent that they are also integral components in a number of important signaling pathways that are regulated by extracellular cues. The activation of Arfs is catalyzed by a family of guanine nucleotide exchange factors (GEFs), referred to as the Sec7 family, based on homology of their catalytic domains to the yeast Arf GEF, sec7p. While there are only six mammalian Arfs, the human genome encodes 15 Sec7 family members, which can be divided into five classes based on related domain organization. Some of this diversity arises from the tissue-specific expression of certain isoforms, but all mammalian cells appear to express at least six Arf GEFs, suggesting that Arf activation is under extensive regulatory control. Here we review recent progress in our understanding of the structure, localization and biology of the different classes of Arf GEFs. PMID- 17850230 TI - Increased SA in NPR1-silenced plants antagonizes JA and JA-dependent direct and indirect defenses in herbivore-attacked Nicotiana attenuata in nature. AB - The phytohormone jasmonic acid (JA) is known to mediate herbivore resistance, while salicylic acid (SA) and non-expressor of PR-1 (NPR1) mediate pathogen resistance in many plants. Herbivore attack on Nicotiana attenuata elicits increases in JA and JA-mediated defenses, but also increases SA levels and Na NPR1 transcripts from the plant's single genomic copy. SA treatment of wild-type plants increases Na-NPR1 and Na-PR1 transcripts. Plants silenced in NPR1 accumulation by RNAi (ir-npr1) are highly susceptible to herbivore and pathogen attack when planted in their native habitat in Utah. They are also impaired in their ability to attract Geocorus pallens predators, due to their decreased ability to release cis-alpha-bergamotene, a JA-elicited volatile 'alarm call'. In the glasshouse, Spodoptera exigua larvae grew better on ir-npr1 plants, which had low levels of JA, JA-isoleucine/leucine, lipoxygenase-3 (LOX3) transcripts and JA elicited direct defense metabolites (nicotine, caffeoyl putrescine and rutin), but high levels of SA and isochorismate synthase (ICS) transcripts, suggesting de novo biosynthesis of SA. A microarray analysis revealed downregulation of many JA elicited genes and upregulation of SA biosynthetic genes. JA treatment restored nicotine levels and resistance to S. exigua in ir-npr1 plants. We conclude that, during herbivore attack, NPR1 negatively regulates SA production, allowing the unfettered elicitation of JA-mediated defenses; when NPR1 is silenced, the elicited increases in SA production antagonize JA and JA-related defenses, making the plants susceptible to herbivores. PMID- 17850232 TI - Urodynamic evidence of successful rehabilitation of a severely contracted bladder after renal transplantation. PMID- 17850231 TI - In vivo magnetic resonance imaging of vascularization in islet transplantation. AB - To evaluate changes in neovascularization of transplanted islets in vivo, dynamic contrast (gadolinium) enhanced magnetic resonance imaging (MRI) was used. Both iron (Feridex)-labeled and unlabeled syngeneic murine subcapsular islet grafts were studied. Differences in dynamic contrast enhancement of islet grafts were quantified after gadolinium injection at post-transplant days 3 and 14. Normalized contrast concentrations at day 14 in transplanted islets were increased relative with that on day 3. Time to peak contrast enhancement was faster by 12 min at day 14 compared to day 3 islets (while kidney and muscle peak times remained the same). Areas under the curve for contrast concentration versus time plots were larger in 14-day relative to 3-day islet grafts. In conclusion, noninvasive assessment of neovascularization is achievable. In vivo dynamic contrast-enhanced MRI can be used to detect and quantify changes in vascularization following islet transplantation. This technique may be useful in developing pro-angiogenic strategies to improve the transplantation outcome in experimental and clinical settings. PMID- 17850233 TI - Hepatic veno-occlusive disease after liver transplantation: an unusual case report. PMID- 17850234 TI - Late onset of development of natural anti-nonGal antibodies in infant humans and baboons: implications for xenotransplantation in infants. AB - If an ABO-incompatible heart is transplanted into an infant before natural antibodies have developed to the specific donor carbohydrate A/B antigen(s), then B-cell tolerance to the donor A/B antigen is achieved, and these antibodies never develop. Anti-carbohydrate antibodies play a role in the rejection of wild type (WT) and alpha1,3-galactosyltransferase gene-knockout (GT-KO) pig xenografts. We investigated development of these antibodies in infant baboons and humans. Serum samples from infant baboons (n = 42) and humans (n = 42) were tested by flow cytometry for immunoglobulin M and immunoglobulin G binding to peripheral blood mononuclear cells from WT and GT-KO pigs, and for complement-dependent cytotoxicity. The presence of anti-blood group antibodies was tested in baboon serum. In infant baboons and humans, cytotoxic anti-Galalpha1,3Gal antibodies develop during the first 3 months, and steadily increase with age, whereas cytotoxic anti-nonGal antibodies are either absent or minimal in the majority of cases throughout the first year of life. Anti-blood group antibodies were not detected before 16 weeks of age. Our data suggest GT-KO pig organ/cell transplants could be carried out in early infancy in the absence of preformed cytotoxic anti-nonGalalpha1,3Gal antibodies. PMID- 17850235 TI - Renal transplantation from extended criteria cadaveric donors: problems and perspectives overview. AB - The critical shortage of organs available for renal transplantation has led to the consideration of alternative strategies for increasing the donor pool. Recently, the cadaveric kidney donor pool extended to donors who might have been deemed unsuitable in early times, leading to the concept of marginal donors and more recently to the notion of expanded criteria donors. Such organs are eligible for organ donation but, because of extreme age and other clinical characteristics, are expected to produce allograft at risk for diminished post transplant function. Thus, the challenge is now to reduce the difference between graft outcome from patients grafted with marginal and 'optimal' donors. This implies appropriate transplantation strategies during pre-, peri- and post transplantation phases including reduction of cold ischemia time, recipient selection, adaptation of immunosuppressive drug regimens, increase in nephron mass by dual kidney transplantation, and improvement in the graft selection process using histological criteria. This review summarizes current definition of a marginal donor and provides some guidance for clinical management of such transplant. PMID- 17850236 TI - Pharmacodynamic cyclosporine A-monitoring: relation of gene expression in lymphocytes to cyclosporine blood levels in cardiac allograft recipients. AB - Recently, we established a pharmacodynamic assay to monitor immunosuppressive effectiveness of cyclosporine A (CsA) in patients on standard CsA regimen. The aim of the present study was to extend this correlation to reduced CsA regimen and to compare pharmacodynamic and kinetic parameters to allow prediction of rejections and infections. In 53 heart allograft recipients, nuclear factor of activated T cells (NFAT)-regulated gene expression was quantified at trough (C0) and 2-h post-CsA dose (C2). Gene expression at C2 was calculated relative to C0 (residual gene expression, RGE) or relative to a healthy reference group (absolute gene expression, AGE). RGE correlated with CsA C2-levels in bimodal fashion: above 575 ng/ml correlation was seen with flat regression gradient. Below 575 ng/ml, correlation was excellent with markedly steeper gradient. At C0 in the low-C2 group (<575 ng/ml), AGE remained unchanged, whereas in the high-C2 group (>575 ng/ml) AGE was markedly reduced. In both groups, AGE at C2 was strongly inhibited. In patients contracting infection during follow-up, RGE was lower than in those without infections independent of CsA levels. CsA-monitoring by quantitation of NFAT-regulated gene expression is feasible with standard and reduced CsA regimens. It correlates better with the incidence of infections than measurement of CsA concentrations and might help in avoiding over immunosuppression. PMID- 17850237 TI - Splitting livers - balancing the gain and the pain. AB - Division of donor livers has allowed effective expansion of the donor pool and has been associated with a reduction in the mortality of children awaiting liver transplantation. However, adult recipients of a split graft tend to have inferior transplant survival, compared with recipients of a whole graft. We have analysed the impact of the splitting programme at a particular centre on the life-years lost or gained in both adult and paediatric recipients. We estimate that at 1 year after transplantation, splitting livers has resulted in a gain of five life years for the paediatric recipients with a loss of six adult patient years; at 5 years post-transplant, a gain of 25 life-years for the paediatric recipients balances a loss of 30 life-years for adult recipients. While this analysis is based on a number of assumptions, and so the results must be treated with caution, it does give rise to a number of ethical considerations which require open and public debate. PMID- 17850239 TI - The role of asymmetrical frontal cortical activity in aggression. AB - Aggression correlates with relatively greater left than right frontal electroencephalographic activity (inverse of EEG alpha power). The present experiment extends this research by manipulating frontal asymmetry and examining its effect on aggression. Participants were assigned to increase left frontal activation or increase right frontal activation by contracting their contralateral hand. They then received insulting feedback and played a game in which they could aggress toward the person who insulted them. Right-hand contractions caused greater left than right central and frontal activation and aggression as compared to left-hand contractions. Within the right-hand contraction condition, greater relative left frontal activity was associated with greater aggression. PMID- 17850240 TI - Age effects to negative arousal differ for self-report and electrodermal activity. AB - Affective processing and emotional experience may change with age. Because findings of age differences in affective experiences are mixed even in studies using standardized stimuli, this study assessed age differences along gradual increases in negative arousal. Younger (20-30 years) and older (70-80 years) healthy adults (n=78) viewed 110 neutral to negative pictures (IAPS) while intensity ratings and electrodermal activity were recorded. Results showed that age had opposite effects on intensity ratings and electrodermal activity over gradual increases in normative arousal. Whereas older adults showed greater increases in intensity ratings than younger adults, they showed attenuated electrodermal activity, especially at high negative arousal. Because self-reports of arousal capture various aspects of affective processes (e.g., physiological changes as well as experience), effects of age may vary for these different aspects. PMID- 17850238 TI - Influence of cognitive control and mismatch on the N2 component of the ERP: a review. AB - Recent years have seen an explosion of research on the N2 component of the event related potential, a negative wave peaking between 200 and 350 ms after stimulus onset. This research has focused on the influence of "cognitive control," a concept that covers strategic monitoring and control of motor responses. However, rich research traditions focus on attention and novelty or mismatch as determinants of N2 amplitude. We focus on paradigms that elicit N2 components with an anterior scalp distribution, namely, cognitive control, novelty, and sequential matching, and argue that the anterior N2 should be divided into separate control- and mismatch-related subcomponents. We also argue that the oddball N2 belongs in the family of attention-related N2 components that, in the visual modality, have a posterior scalp distribution. We focus on the visual modality for which components with frontocentral and more posterior scalp distributions can be readily distinguished. PMID- 17850241 TI - Dissociation of neural regions associated with anticipatory versus consummatory phases of incentive processing. AB - Incentive delay tasks implicate the striatum and medial frontal cortex in reward processing. However, prior studies delivered more rewards than penalties, possibly leading to unwanted differences in signal-to-noise ratio. Also, whether particular brain regions are specifically involved in anticipation or consumption is unclear. We used a task featuring balanced incentive delivery and an analytic strategy designed to identify activity specific to anticipation or consumption. Reaction time data in two independent samples (n=13 and n=8) confirmed motivated responding. Functional magnetic resonance imaging revealed regions activated by anticipation (anterior cingulate) versus consumption (orbital and medial frontal cortex). Ventral striatum was active during reward anticipation but not significantly more so than during consumption. Although the study features several methodological improvements and helps clarify the neural basis of incentive processing, replications in larger samples are needed. PMID- 17850242 TI - An investigation of concurrent ERP and self-paced reading methodologies. AB - Traditionally, event-related brain potential (ERP) studies of language processing have presented words at a fixed rate using rapid serial visual presentation. Recent studies suggest, however, that the processes engaged during sentence comprehension are contingent on word presentation rate. These findings underscore the importance of allowing participants to read at a natural pace. The present study employed simultaneous self-paced reading and ERP methodologies to examine behavioral and neural responses while participants read sentences containing pragmatic or morphosyntactic violations or no violations. ERP and self-paced reading results replicated previous findings. This novel combination of behavioral and ERP methodologies combines the high temporal resolution and direct neural measures offered by ERPs with the more natural reading environment and information about processing load provided by self-paced reading. PMID- 17850243 TI - Investigating dimensional organization in scripts using the pupillary response. AB - Scripts are mental representations of activities in memory and are thought to be organized dimensionally in a temporal dimension. We investigated the cognitive strategies during the processing of temporal order of an event sequence to gain insight into the organization of scripts. Subjects were presented with triplets of script events (A - B - C). Fifty percent of the items included sequence violations at different positions within the triplet (late: A - C - B, or early: C - A - B). Reaction times indicate that subjects use an economical strategy by comparing the relative temporal positions of event pairs (e.g., A vs. B and if necessary B vs. C) and only attend to information that is necessary. Pupil data and error rates indicate that the temporal information of the complete sequence affects the decision process even if the first event pair indicates that temporal order has been violated. Results are seen as evidence of a dimensional structure of scripts. PMID- 17850244 TI - Do ERP components triggered during attentional orienting represent supramodal attentional control? AB - Lateralized ERP components triggered during cued shifts of spatial attention (anterior directing attention negativity [ADAN], late directing attention positivity [LDAP]) have been observed during visual, auditory, and tactile attention tasks, suggesting that these components reflect supramodal attentional control processes. This interpretation has recently been called into question by the finding that the ADAN is absent in response to auditory attention cues. Here we demonstrate that ADAN and LDAP components are reliably elicited in a purely unimodal auditory attention task where auditory cues are followed by auditory imperative stimuli. The fact that the ADAN is not restricted to task contexts where visual or tactile stimuli are relevant is consistent with the hypothesis that this component is linked to supramodal attentional control. PMID- 17850245 TI - Effects of arterial and cardiopulmonary baroreceptor activation on simple and choice reaction times. AB - Variations in simple reaction time over the cardiac cycle could be due to cortical inhibition associated with activation of the arterial baroreceptors. It has been proposed that higher order cognitive processing may also be modulated and, moreover, that cardiopulmonary baroreceptors may have similar inhibitory effects. This study examined arterial and cardiopulmonary baroreceptor effects on simple and choice reaction times by presenting visual stimuli at one of six intervals after the R-wave of the electrocardiogram (0, 150, 300, 450, 600, 750 ms) while participants lay supine with their legs raised or lowered. Reaction times were slower early in the cardiac cycle compared to later whereas reaction time slopes were not different. No cardiopulmonary baroreceptor effects were found. Cardiac cycle effects on reaction time are consistent with the arterial baroreceptor hypothesis and appear to be confined to lower order sensory-motor processing. PMID- 17850246 TI - Unusual presentation of cytomegalovirus enteritis after liver and kidney transplantation. AB - Cytomegalovirus (CMV) is a cause of significant morbidity and mortality in solid organ transplant recipients. Gastrointestinal (GI) tract infection by CMV in this population can cause symptomatic disease, which typically manifests as fever, abdominal pain, nausea, and bloody diarrhea. Erosive lesions of the GI mucosa are often evident on endoscopic exam. We report an unusual presentation of CMV enteritis in a kidney and liver transplant recipient with the development of acute onset voluminous watery diarrhea in the absence of other typical symptoms and subsequent progression to hypovolemic shock and acute renal failure. This case emphasizes the atypical presentations of common opportunistic infections that may occur in immunosuppressed hosts. PMID- 17850247 TI - Cutaneous manifestations of cytomegalovirus disease in renal transplant recipients: a case series. AB - Cytomegalovirus (CMV) is an important and well-described opportunistic virus in the immunocompromised host, with infection occurring mainly after the first month in the new renal transplant recipient. CMV can present as primary infection, reinfection, or reactivation of latent disease. It is capable of protean manifestations. Cutaneous manifestations are variable, rare, and diagnosis often delayed. We present 3 cases of cutaneous CMV disease in renal transplant recipients. Manifestations in our patients included ulceration of the tongue and perianal areas, facial petechiae, and nodular lesion involving the ear. This case series serves to highlight the importance of early skin biopsy in the diagnosis and management of cutaneous CMV disease. PMID- 17850248 TI - Adaxial/abaxial specification in the regulation of photosynthesis and stomatal opening with respect to light orientation and growth with CO2 enrichment in the C4 species Paspalum dilatatum. AB - Whole-plant morphology, leaf structure and composition were studied together with the effects of light orientation on the dorso-ventral regulation of photosynthesis and stomatal conductance in Paspalum dilatatum cv. Raki plants grown for 6 wk at either 350 or 700 microl l(-1) CO(2). Plant biomass was doubled as a result of growth at high CO(2) and the shoot:root ratio was decreased. Stomatal density was increased in the leaves of the high CO(2)-grown plants, which had greater numbers of smaller stomata and more epidermal cells on the abaxial surface. An asymmetric surface-specific regulation of photosynthesis and stomatal conductance was observed with respect to light orientation. This was not caused by dorso-ventral variations in leaf structure, the distribution of phosphoenolpyruvate carboxylase (PEPC) and ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) proteins or light absorptance, transmittance or reflectance. Adaxial/abaxial specification in the regulation of photosynthesis results from differential sensitivity of stomatal opening to light orientation and fixed gradients of enzyme activation across the leaf. PMID- 17850249 TI - Can hybridization cause local extinction: a case for demographic swamping of the Australian native Senecio pinnatifolius by the invasive Senecio madagascariensis? AB - Hybridization between native and invasive species can have several outcomes, including enhanced weediness in hybrid progeny, evolution of new hybrid lineages and decline of hybridizing species. Whether there is a decline of hybridizing species largely depends on the relative frequencies of parental taxa and the viability of hybrid progeny. Here, the individual- and population-level consequences of hybridization between the Australian native Senecio pinnatifolius and the exotic Senecio madagascariensis were investigated with amplified fragment length polymorphism (AFLP) markers, and this information was used to estimate the annual loss of viable seeds to hybridization. A high frequency (range 8.3-75.6%) of hybrids was detected in open pollinated seeds of both species, but mature hybrids were absent from sympatric populations. A hybridization advantage was observed for S. madagascariensis, where significantly more progeny than expected were sired based on proportional representation of the two species in sympatric populations. Calculations indicated that S. pinnatifolius would produce less viable seed than S. madagascariensis, if hybridization was frequency dependent and S. madagascariensis reached a frequency of between 10 and 60%. For this native-exotic species pair, prezygotic isolating barriers are weak, but low hybrid viability maintains a strong postzygotic barrier to introgression. As a result of asymmetric hybridization, S. pinnatifolius would appear to be under threat if S. madagascariensis increases numerically in areas of contact. PMID- 17850250 TI - Origin and dissemination of the pollen-part mutated SC haplotype which confers self-compatibility in apricot (Prunus armeniaca). AB - In China, its centre of origin, apricot (Prunus armeniaca) is self-incompatible. However, most European cultivars are self-compatible. In most cases, self compatibility is a result of a loss-of-function mutation within the pollen gene (SFB) in the SC haplotype. Controlled pollinations performed in this work revealed that the cross 'Cegledi orias' (S8S9)x'Cegledi arany' (SCS9) set well, as expected, but the reciprocal cross did not. Apricot S8, S9 and SC haplotypes were analysed using a multilevel approach including fruit set evaluation, pollen tube growth analysis, RNase activity assays, polymerase chain reaction (PCR) analysis and DNA sequencing of the S-RNase and SFB alleles. SFB8 was revealed to be the first known progenitor allele of a naturally occurring self-compatibility allele in Prunus, and consequently SC=The first intron of SC-RNase is a phase one intron, indicating its more recent evolutionary origin compared with the second intron. Sequence analysis of different cultivars revealed that more single nucleotide polymorphisms accumulated in SC-RNase than in SFBC. New methods were designed to allow high-throughput analysis of S genotypes of apricot cultivars and selections. S-RNase sequence data from various sources helped to elucidate the putative origin and dissemination of self-compatibility in apricot conferred by the SC haplotype. PMID- 17850251 TI - Hybrid weakness controlled by the dosage-dependent lethal (DL) gene system in common bean (Phaseolus vulgaris) is caused by a shoot-derived inhibitory signal leading to salicylic acid-associated root death. AB - Certain crosses of common bean (Phaseolus vulgaris) result in temperature dependent hybrid weakness associated with a severe root phenotype. This is controlled by the interaction of the root- and shoot-expressed semidominant alleles dosage-dependent lethal 1 (DL(1)) and DL(2), which communicate via long distance signaling. Previously, apparent reciprocal effects on root growth and the restoration of normal root growth by exogenous sucrose led to the hypothesis that the dosage-dependent lethal (DL) system may control root-shoot carbon partitioning. Here, recombinant inbred lines were used to map the DL loci and physiological and biochemical analysis, including metabolite profiling, was used to gain new insights into the signaling interaction and the root phenotype. It is shown that the DL system does not control root-shoot carbon partitioning and that roots are unlikely to die from carbon starvation. Instead, root death likely occurs by defense-related programmed cell death, as indicated by salicylic acid accumulation. DL(2)-expressing cotyledons supply a potent inhibitory signal that is sufficient to cause such death in DL(1)-expressing roots. These data implicate the DL system in defense-related signaling and provide support for the recent hypothesis of defense-related autoimmunity as a potential isolating mechanism in plant speciation, in particular, setting a precedence for the potential roles of long-distance signaling and temperature dependence. PMID- 17850253 TI - Gradual activation of the response regulator DegU controls serial expression of genes for flagellum formation and biofilm formation in Bacillus subtilis. AB - In natural environments, bacteria fluctuate between growth as motile cells and growth as sessile, biofilm-forming cells. However, what controls the transition between these two-growth modes in Bacillus subtilis is not well understood yet. The degU mutation prevents both flagellum formation and biofilm formation, suggesting that one of the transition mechanisms may underlie regulation of the DegU activity. The expression profiles of DegU-regulated genes differed; flagellar genes and several unknown genes were expressed during the exponential phase, whereas other genes were induced in the stationary phase. The degS mutation did not affect transcription of the flgB-sigD operon, but reduced transcription of sigma(D)-dependent flagellar genes, degU and other DegU regulated genes. In addition, the degQ mutation did not affect transcription of flagellar genes but reduce transcription of other DegU-regulated genes. Purified DegQ protein stimulated phosphotransfer from phospho-DegS to DegU in vitro. Moreover, DegU binds the promoter region of flgB with a high affinity, whereas DegU binds to the promoter regions of other DegU-regulated genes with a low affinity and in a DegS-dependent manner. Taken together, we propose that a gradual increase in DegU and phospho-DegU levels induces a transition from growth as motile cells to growth as sessile, biofilm-forming cells. PMID- 17850252 TI - Mutational analysis reveals Escherichia coli oriC interacts with both DnaA-ATP and DnaA-ADP during pre-RC assembly. AB - Prior to initiating DNA synthesis, Escherichia coli oriC switches from ORC, comprising initiator DnaA bound at three high-affinity sites, to pre-RC, when additional DnaA molecules interact with low-affinity sites. Two types of low affinity sites exist: R boxes that bind DnaA-ATP and DnaA-ADP with equal affinity, and I-sites with a three- to fourfold preference for DnaA-ATP. To assess the regulatory role of weak DnaA interactions during pre-RC assembly in vivo, we compared the behaviour of plasmid-borne wild-type oriC with mutants having an increased or decreased number of DnaA-ATP discriminatory I-sites. Increasing the number of discriminatory sites by replacing R5M with I2 inactivated extrachromosomal oriC function. Mutants with no discriminatory sites perturbed host growth and rapidly replaced wild-type chromosomal oriC, but normal function returned if one I-site was restored at either the I2, I3 or R5M position. These observations are consistent with assembly of E. coli pre-RC in vivo from mixtures of DnaA-ATP and DnaA-ADP, with I-site interactions coupling pre-RC assembly to DnaA-ATP levels. PMID- 17850255 TI - A biosynthetic gene cluster for a secreted cellobiose lipid with antifungal activity from Ustilago maydis. AB - The phytopathogenic basidiomycetous fungus Ustilago maydis secretes large amounts of the glycolipid biosurfactant ustilagic acid (UA). UA consists of 15,16 dihydroxypalmitic or 2,15,16-trihydroxypalmitic acid, which is O-glycosidically linked to cellobiose at its terminal hydroxyl group. In addition, the cellobiose moiety is acetylated and acylated with a short-chain hydroxy fatty acid. We have identified a 58 kb spanning gene cluster that contains 12 open reading frames coding for most, if not all, enzymes needed for UA biosynthesis. Using a combination of genetic and mass spectrometric analysis we were able to assign functional roles to three of the proteins encoded by the gene cluster. This allowed us to propose a biosynthesis route for UA. The Ahd1 protein belongs to the family of non-haem diiron reductases and is required for alpha-hydroxylation of palmitic acid. Two P450 monooxygenases, Cyp1 and Cyp2, catalyse terminal and subterminal hydroxylation of palmitic acid. We could demonstrate that infection of tomato leaves by the plant pathogenic fungus Botrytis cinerea is prevented by co-inoculation with wild-type U. maydis sporidia. U. maydis mutants defective in UA biosynthesis were unable to inhibit B. cinerea infection indicating that UA secretion is critical for antagonistic activity. PMID- 17850254 TI - RrgA is a pilus-associated adhesin in Streptococcus pneumoniae. AB - Adherence to host cells is important in microbial colonization of a mucosal surface, and Streptococcus pneumoniae adherence was significantly enhanced by expression of an extracellular pilus composed of three subunits, RrgA, RrgB and RrgC. We sought to determine which subunit(s) confers adherence. Bacteria deficient in RrgA are significantly less adherent than wild-type organisms, while overexpression of RrgA enhances adherence. Recombinant monomeric RrgA binds to respiratory cells, as does RrgC with less affinity, and pre-incubation of epithelial cells with RrgA reduces adherence of wild-type piliated pneumococci. Non-adherent RrgA-negative, RrgB- and RrgC-positive organisms produce pili, suggesting that pilus-mediated adherence is due to expression of RrgA, rather than the pilus backbone itself. In contrast, RrgA-positive strains with disrupted rrgB and rrgC genes exhibit wild-type adherence despite failure to produce pili by Western blot or immunoelectron microscopy. The density of bacteria colonizing the upper respiratory tract of mice inoculated with piliated RrgA-negative pneumococci was significantly less compared with wild-type; in contrast, non piliated pneumococci expressing non-polymeric RrgA had similar numbers of bacteria in the nasopharynx as piliated wild-type bacteria. These data suggest that RrgA is central in pilus-mediated adherence and disease, even in the absence of polymeric pilus production. PMID- 17850256 TI - Aerobic TMAO respiration in Escherichia coli. AB - In the absence of oxygen, Escherichia coli can use alternative exogenous electron acceptors, including trimethylamine oxide (TMAO), to generate energy. In this study, we showed that in contrast to the other anaerobic respiratory systems, the TMAO reductase (Tor) system was expressed during both aerobiosis and anaerobiosis. By using a torA-lacZ fusion and quantitative reverse transcription polymerase chain reaction, we established that the torCAD operon encoding the Tor system was induced in the presence of TMAO mainly during exponential phase, and that optimal induction required a certain level of DNA supercoiling. We also showed that the presence of oxygen prevented neither the biogenesis of the Tor system nor the reduction of TMAO. The physiological role of TMAO reduction during aerobiosis has not been yet established, but our experiments suggest that alkaline TMA production could enhance the growth conditions by increasing the pH of the culture. PMID- 17850258 TI - Effects of physical connection and genetic identity of neighbouring ramets on root-placement patterns in two clonal species. AB - Root-placement patterns were examined in the clonal species Glechoma hederacea and Fragaria vesca when grown with different types of neighbours. Three different patterns were predicted as consequences of different types of interactions between roots: the avoidance pattern if root growth decreases in the presence of neighbouring roots; the intrusive pattern if root growth increases towards neighbouring roots; and the unresponsive pattern if root growth is unaffected by neighbouring roots. Experiments were conducted in which physical connection between ramets, and the genetic identity of neighbouring ramets, were manipulated. The patterns of distribution of entire root systems and elongation rates of individual roots were measured. Root systems and individual roots of G. hederacea avoided contact with roots of neighbouring ramets, irrespective of connection to the neighbour and its genetic or specific identity. In contrast, F. vesca roots grew equally towards and away from intraspecific ramet neighbours and their elongation was stimulated by contact with roots of G. hederacea ramets. These results demonstrate that root-placement patterns of plants grown with different types of neighbours vary between species, and suggest that factors additional to resource depletion could be involved in their development. PMID- 17850257 TI - Genome-wide analysis of T-DNA integration into the chromosomes of Magnaporthe oryzae. AB - Agrobacterium tumefaciens-mediated transformation (ATMT) has become a prevalent tool for functional genomics of fungi, but our understanding of T-DNA integration into the fungal genome remains limited relative to that in plants. Using a model plant-pathogenic fungus, Magnaporthe oryzae, here we report the most comprehensive analysis of T-DNA integration events in fungi and the development of an informatics infrastructure, termed a T-DNA analysis platform (TAP). We identified a total of 1110 T-DNA-tagged locations (TTLs) and processed the resulting data via TAP. Analysis of the TTLs showed that T-DNA integration was biased among chromosomes and preferred the promoter region of genes. In addition, irregular patterns of T-DNA integration, such as chromosomal rearrangement and readthrough of plasmid vectors, were also observed, showing that T-DNA integration patterns into the fungal genome are as diverse as those of their plant counterparts. However, overall the observed junction structures between T DNA borders and flanking genomic DNA sequences revealed that T-DNA integration into the fungal genome was more canonical than those observed in plants. Our results support the potential of ATMT as a tool for functional genomics of fungi and show that the TAP is an effective informatics platform for handling data from large-scale insertional mutagenesis. PMID- 17850259 TI - Chaperones specific for the membrane-bound [NiFe]-hydrogenase interact with the Tat signal peptide of the small subunit precursor in Ralstonia eutropha H16. AB - Periplasmic membrane-bound [NiFe]-hydrogenases undergo a complex maturation pathway, including cofactor incorporation, subunit assembly, and finally twin arginine-dependent membrane translocation (Tat). In this study, the role of the two accessory proteins HoxO and HoxQ in the maturation of the membrane-bound [NiFe]-hydrogenase (MBH) of Ralstonia eutropha H16 was investigated. MBH activity was absent in soluble as well as membrane fractions of cells with deletions in the respective genes. The absence of HoxO and HoxQ led to degradation of the small subunit precursor (preHoxK) of the MBH. The two accessory proteins directly interacted with preHoxK prior to assembly of active MBH dimer in the cytoplasm. MBH mutants with modified Tat signal peptides were disrupted in preHoxK/HoxO/HoxQ complex formation. Isolated HoxO and HoxQ proteins formed a complex in vitro with the chemically synthesized HoxK Tat signal peptide. Two functions of the two chaperones are discussed: (i) protection of the Fe-S cluster containing HoxK subunit under oxygenic conditions, and (ii) avoidance of HoxK export prior to dimerization with the large MBH subunit HoxG. PMID- 17850260 TI - Transketolase A, an enzyme in central metabolism, derepresses the marRAB multiple antibiotic resistance operon of Escherichia coli by interaction with MarR. AB - The Escherichia coli marRAB operon specifies two regulatory proteins, MarR (which represses) and MarA (which activates expression of the operon). The latter controls expression of multiple other chromosomal genes implicated in cell physiology, multiple drug resistance and virulence. Using randomly cloned E. coli DNA fragments in the bacterial adenylate cyclase two-hybrid system, we found that transketolase A (TktA) interacts with MarR. Purified (6H)-TktA immobilized on NiNTA resin-bound MarR. Overexpression or deletion of tktA showed that TktA interfered with MarR repression of the marRAB operon. Deletion of tktA increased antibiotic and oxidative stress susceptibilities, while its overexpression decreased them. Hydrogen peroxide induced tktA at 1 h treatment, while an increase in marRAB expression occurred only after 3 h exposure. This increase was dependent on the presence of tktA. Two MarR mutations which eliminated MarR binding to the marRAB operator and one which decreased dimerization of MarR had no effect on MarR interaction with TktA in the two-hybrid system. However, the interaction was disrupted by one of the three tested superrepressor mutant MarR proteins known to increase MarR binding to DNA. TktA inhibition of repression by MarR demonstrates a previously unrecognized level of control of the expression of marRAB operon. PMID- 17850261 TI - Mechanism of hcnA mRNA recognition in the Gac/Rsm signal transduction pathway of Pseudomonas fluorescens. AB - In the plant-beneficial bacterium Pseudomonas fluorescens CHA0, the expression of antifungal exoproducts is controlled by the GacS/GacA two-component system. Two RNA binding proteins (RsmA, RsmE) ensure effective translational repression of exoproduct mRNAs. At high cell population densities, GacA induces three small RNAs (RsmX, RsmY, RsmZ) which sequester both RsmA and RsmE, thereby relieving translational repression. Here we systematically analyse the features that allow the RNA binding proteins to interact strongly with the 5' untranslated leader mRNA of the P. fluorescens hcnA gene (encoding hydrogen cyanide synthase subunit A). We obtained evidence for three major RsmA/RsmE recognition elements in the hcnA leader, based on directed mutagenesis, RsmE footprints and toeprints, and in vivo expression data. Two recognition elements were found in two stem-loop structures whose existence in the 5' leader region was confirmed by lead(II) cleavage analysis. The third recognition element, which overlapped the hcnA Shine Dalgarno sequence, was postulated to adopt either an open conformation, which would favour ribosome binding, or a stem-loop structure, which may form upon interaction with RsmA/RsmE and would inhibit access of ribosomes. Effective control of hcnA expression by the Gac/Rsm system appears to result from the combination of the three appropriately spaced recognition elements. PMID- 17850262 TI - Microarray analysis of Mu transposition in Salmonella enterica, serovar Typhimurium: transposon exclusion by high-density DNA binding proteins. AB - All organisms contain transposons with the potential to disrupt and rearrange genes. Despite the presence of these destabilizing sequences, some genomes show remarkable stability over evolutionary time. Do bacteria defend the genome against disruption by transposons? Phage Mu replicates by transposition and virtually all genes are potential insertion targets. To test whether bacteria limit Mu transposition to specific parts of the chromosome, DNA arrays of Salmonella enterica were used to quantitatively measure target site preference and compare the data with Escherichia coli. Essential genes were as susceptible to transposon disruption as non-essential ones in both organisms, but the correlation of transposition hot spots among homologous genes was poor. Genes in highly transcribed operons were insulated from transposon mutagenesis in both organisms. A 10 kb cold spot on the pSLT plasmid was near parS, a site to which the ParB protein binds and spreads along DNA. Deleting ParB erased the plasmid cold spot, and an ectopic parS site placed in the Salmonella chromosome created a new cold spot in the presence of ParB. Our data show that competition between cellular proteins and transposition proteins on plasmids and the chromosome is a dominant factor controlling the genetic footprint of transposons in living cells. PMID- 17850263 TI - Pho85, a multifunctional cyclin-dependent protein kinase in budding yeast. AB - Pho85 is a multifunctional cyclin-dependent kinase (Cdk) in Saccharomyces cerevisiae that has emerged as an important model for the role of Cdks in both cell cycle control and other processes. Pho85 is targeted to its substrates by 10 different cyclins or Pcls. Three of these Pcls have specific roles in G1 phase of the cell cycle, both in regulating G1-specific gene expression and in controlling polarized growth. Many known substrates of the G1 forms of Pho85 are also phosphorylated by the homologous Cdk Cln-Cdc28, suggesting parallel or overlapping roles. Most of the remaining Pcls function in signalling: Pho85 is generally active when environmental conditions are satisfactory, phosphorylating proteins involved in transcription and other regulatory events to keep the stress response and inappropriate activities turned off. Recently, genetic screens for synthetic lethality and synthetic dosage lethality, and proteomic screens for in vitro Pho85 substrates, have revealed more details about how Pho85 functions to regulate a variety of cellular processes. PMID- 17850264 TI - Restrictive mating by females on black grouse leks. AB - In bird species with pair bonds, extra-pair matings could allow females to choose genetically superior males. This is not needed in lekking species because female choice is not constrained by pairing opportunities. However, polyandry has been reported in most lekking species studied so far. Using 12 microsatellite loci, we determined the paternity of 135 broods of black grouse sampled between 2001 and 2005 (970 hatchlings and 811 adult birds genotyped). The paternity assignments were combined to lek observations to investigate the mating behaviour of black grouse females. About 10% of the matings seemed to take place with males displaying solitarily. Forty per cent of the copulations between males displaying on the studied leks and radio-tagged females were not recorded. This was due to difficulties in identifying the females and because our observations did not cover all the possible time for matings. However, females of the undetected copulations had chosen males that were already known to be successful on the leks. There was a strong consistency between the observations and true paternity, even when the copulation was disturbed by a neighbouring male. Multiple mating and multiple paternities were rare. We can now confidently ascertain that most females mate only once with one male for the whole clutch. This mating behaviour requires that a single insemination is sufficient to fertilize a clutch and that females can determine whether the sperm has been successfully transferred. Grouse Tetraoninae with many lekking species may be the only bird taxon that has evolved these traits. PMID- 17850265 TI - Genetic isolation and cryptic variation within the Lycaena xanthoides species group (Lepidoptera: Lycaenidae). AB - Species exist as biological entities with patterns of discontinuous phenotypic variation. However, the distinctness of taxa is called into question when morphological intermediates exist in areas of sympatry, reflecting either gene flow among variants of a species or hybridization between different species. Studying the partitioning of genetic variation provides a means to discern between the two possibilities. We used genetic and morphometric approaches to investigate the degree of isolation among the three members of the Lycaena xanthoides species group. Lycaena xanthoides, L. editha, and L. dione are predominantly allopatric and have been treated both as three separate species and as a single polytypic species. Using 618 bp of the mitochondrial gene COII, we found little phylogenetic resolution, but significant among-taxa genetic variance partitioning. Divergence among these taxa has been relatively recent, as evidenced by relatively low pairwise sequence divergence. Also, the existence of two well-supported clades within L. xanthoides sensu stricto, concordant with the Transverse Ranges of southern California, indicates divergence within this taxon, and a possible cryptic species. Significant morphological differentiation between L. editha and L. xanthoides supports the hypothesis that these taxa represent separate gene pools. Populations occurring in a narrow zone where the two species' ranges approach are characterized by intermediate morphology, suggesting incomplete morphological divergence or recent hybridization. These findings highlight the utility of genetic data in inferring species boundaries and the identification of cryptic lineages. PMID- 17850266 TI - Collapse following gastrointestinal bleeding secondary to a congenital duodenal diverticulum in two littermate boxer pups. AB - Two littermates, a young male and female boxer, were admitted to the Utrecht University's Department of Clinical Sciences of Companion Animals within a three month period. Both dogs suffered from anaemia caused by chronic intestinal blood loss, vomiting and weight loss. In both cases, there was no response to conservative medical management. Eventually, the dogs suffered significant gastrointestinal haemorrhage that resulted in collapse. Gastroduodenoscopy and exploratory surgery showed a duodenal diverticulum in both dogs. This is the first report that describes this congenital anomaly in two siblings. PMID- 17850267 TI - First report of canine African trypanosomosis in the UK. AB - A six-year-old neutered male Jack Russell terrier was presented two years after importation into the UK from southern Africa with severe anaemia and abdominal distension. Abdominal ultrasonography revealed the presence of hepato splenomegaly and ascites. A diagnosis of trypanosomosis was made by blood smear examination. Shortly after admission the dog collapsed and died. PCR analysis revealed a single infection with Trypanosoma congolense savannah type. This is the first reported case of canine African trypanosomosis in Europe and suggests that chronic trypanosomosis may allow importation of the disease in apparently asymptomatic animals, even with extended quarantine periods. PMID- 17850268 TI - The origins of weedy rice. AB - Where do weeds come from? How do they evolve from nonweedy ancestors? In this issue of Molecular Ecology, Londo and Schaal examine the origin of weedy rice (Oryza sativa) populations in the USA. Analysing nuclear DNA sequence and microsatellite data, they show the importance of parallel evolution, hybridization, gene flow, and migration in the evolution of these weeds. PMID- 17850269 TI - Genetic response to rapid climate change: it's seasonal timing that matters. AB - The primary nonbiological result of recent rapid climate change is warming winter temperatures, particularly at northern latitudes, leading to longer growing seasons and new seasonal exigencies and opportunities. Biological responses reflect selection due to the earlier arrival of spring, the later arrival of fall, or the increasing length of the growing season. Animals from rotifers to rodents use the high reliability of day length to time the seasonal transitions in their life histories that are crucial to fitness in temperate and polar environments: when to begin developing in the spring, when to reproduce, when to enter dormancy or when to migrate, thereby exploiting favourable temperatures and avoiding unfavourable temperatures. In documented cases of evolutionary (genetic) response to recent, rapid climate change, the role of day length (photoperiodism) ranges from causal to inhibitory; in no case has there been demonstrated a genetic shift in thermal optima or thermal tolerance. More effort should be made to explore the role of photoperiodism in genetic responses to climate change and to rule out the role of photoperiod in the timing of seasonal life histories before thermal adaptation is assumed to be the major evolutionary response to climate change. PMID- 17850270 TI - Molecular and quantitative trait variation across the native range of the invasive species Hypericum canariense: evidence for ancient patterns of colonization via pre-adaptation? AB - To understand the success of invasive species, it is important to know whether colonization events are facilitated by adaptive evolution or are limited to sites where a species is pre-adapted to thrive. Studies of the ancient colonization patterns of an invader in its native range provide an opportunity to examine its natural history of adaptation and colonization. This study uses molecular (internal transcribed spacer sequence and amplified fragment length polymorphism) and common garden approaches to assess the ancient patterns of establishment and quantitative trait evolution in the invasive shrub Hypericum canariense. This species has an unusually small and discrete native range in the Canary Islands. Our data reveal two genetic varieties with divergent life histories and different colonization patterns across the islands. Although molecular divergence within each variety is large (pairwise FST from 0.18 to 0.32 between islands) and nearly as great as divergence between them, life-history traits show striking uniformity within varieties. The discrepancy between molecular and life-history trait divergence points to the action of stabilizing selection within varieties and the influence of pre-adaptation on patterns of colonization. The colonization history of H. canariense reflects how the relationship between selective environments in founding and source populations can dictate establishment by particular lineages and their subsequent evolutionary stasis or change. PMID- 17850272 TI - Shared quantitative trait loci underlying the genetic correlation between continuous traits. AB - We review genetic correlations among quantitative traits in light of their underlying quantitative trait loci (QTL). We derive an expectation of genetic correlation from the effects of underlying loci and test whether published genetic correlations can be explained by the QTL underlying the traits. While genetically correlated traits shared more QTL (33%) on average than uncorrelated traits (11%), the actual number of shared QTL shared was small. QTL usually predicted the sign of the correlation with good accuracy, but the quantitative prediction was poor. Approximately 25% of trait pairs in the data set had at least one QTL with antagonistic effects. Yet a significant minority (20%) of such trait pairs have net positive genetic correlations due to such antagonistic QTL 'hidden' within positive genetic correlations. We review the evidence on whether shared QTL represent single pleiotropic loci or closely linked monotropic genes, and argue that strict pleiotropy can be viewed as one end of a continuum of recombination rates where r=0. QTL studies of genetic correlation will likely be insufficient to predict evolutionary trajectories over long time spans in large panmictic populations, but will provide important insights into the trade-offs involved in population and species divergence. PMID- 17850273 TI - Treatment of pancreatitis-associated extrahepatic biliary tract obstruction by choledochal stenting in seven cats. AB - OBJECTIVES: To report the clinicopathological findings and outcome in cats with pancreatitis-associated extrahepatic biliary tract obstruction (EHBO) treated by choledochal tube stenting. METHODS: Medical records of cats with EHBO secondary to pancreatitis that underwent choledochal stenting were reviewed. Information on outcome was obtained by re-examination of the cat or by telephone interview with the owners. RESULTS: All cats had pancreatitis confirmed by histopathological examination of biopsy samples (n=6) or suspected based on gross examination at surgery (n=1). In six cats, a section of 3.5 to five French gauge red rubber catheter and in one cat a section of 22 G intravenous catheter were used as a choledochal stent. Two cats developed re-obstruction of the biliary tract within a week of the original surgery. One cat had confirmed episodes of ascending cholangitis postoperatively. Two cats had chronic intermittent vomiting in the postoperative period. Two cats died during the perioperative period. Five cats survived to discharge, three of which died seven to 24 months postoperatively and two of which remain alive to date. CLINICAL SIGNIFICANCE: Choledochal stenting is an alternative to biliary diversion for management of feline pancreatitis associated EHBO in select cases. However, there may be greater morbidity with this technique in cats compared with dogs. PMID- 17850274 TI - Methaemoglobinaemia caused by hydroxycarbamide (hydroxyurea) ingestion in a dog. AB - A three-year-old female neutered greyhound was presented after ingestion of its owner's hydroxycarbamide (hydroxyurea) tablets. The dog was found to be cyanosed, and methaemoglobinaemia was demonstrated by co-oximetry. Therapy included methylene blue, oxygen, packed red blood cell transfusion, N-acetylcysteine and crystalloid fluids. Methaemoglobinaemia resolved within 16 hours. Granulocyte colony-stimulating factor was administered for five days in an attempt to prevent severe neutropenia. Mild delayed transient myelotoxicity was suspected. The dog made a full recovery. PMID- 17850275 TI - A retrospective study of 61 cases of spontaneous canine epistaxis (1998 to 2001). AB - OBJECTIVES: To determine the prevalence and identify possible clinicopathologic indicators of the diseases associated with canine epistaxis. METHODS: The medical records of 61 dogs with epistaxis were reviewed. RESULTS: Systemic diseases, diagnosed in fifty-six dogs, included canine leishmaniasis in twenty-three dogs, canine monocytic ehrlichiosis in twenty-two, concurrent canine leishmaniasis and canine monocytic ehrlichiosis in six, rodenticide toxicity in two and primary immune-mediated thrombocytopenia, suspected oestrogen toxicity and systemic arterial hypertension in one dog each. Intranasal diseases were documented in the remaining five dogs, including transmissible venereal tumour in three dogs, and nasal adenocarcinoma and nasal aspergillosis in one dog each. Mucosal pallor and a generalised bleeding tendency were significantly more common among dogs with canine monocytic ehrlichiosis compared with those with canine leishmaniasis, whereas the opposite was true for peripheral lymphadenomegaly. Also, dogs with canine monocytic ehrlichiosis presented with pancytopenia more frequently compared with those with canine leishmaniasis; in the latter dogs, the median values of haematocrit, leucocyte and platelet counts and serum total protein concentrations were higher. CLINICAL SIGNIFICANCE: Canine leishmaniasis and canine monocytic ehrlichiosis are the leading causes of canine epistaxis in Greece. Mucosal pallor, bleeding tendency and pancytopenia are more likely to be indicative of canine monocytic ehrlichiosis, as opposed to peripheral lymphadenomegaly and hyperproteinaemia in canine leishmaniasis. PMID- 17850276 TI - Antibiotic susceptibility of bacteria isolated from cats with ulcerative keratitis in Taiwan. AB - OBJECTIVES: To assess the antibiotic susceptibility of bacteria isolated from corneal ulcers in cats. METHODS: A total of 92 cats with infected corneal ulcers were swabbed for bacterial culture and the antibiotic sensitivity of the isolates analysed. RESULTS: Bacteria were isolated from 54 of 92 infected eyes with corneal ulcers and purulent discharge. A total of 59 bacterial isolates were obtained from the 54 ulcers. The ratio of Gram-positive to Gram-negative isolates was approximately 3:1. The most commonly isolated Gram-positive bacteria were Staphylococcus species (51 per cent of all isolates), while Pseudomonas aeruginosa (13.5 per cent of all isolates) was the most common Gram-negative bacteria isolated. The Gram-negative isolates demonstrated a greater incidence of antibiotic resistance than the Gram-positive ones. The most effective antibiotics against the isolates were ciprofloxacin, tobramycin and gentamicin, with erythromycin and lincomycin showing the greatest number of resistant isolates. CLINICAL SIGNIFICANCE: Staphylococcus and Pseudomonas species were the most common Gram-positive and Gram-negative bacteria, respectively, isolated from feline eyes with ulcerative keratitis. The second-generation fluoroquinolone, ciprofloxacin and the aminoglycoside gentamicin were found to be highly effective against the majority of isolates. PMID- 17850277 TI - The use of magnetic resonance imaging in the management of pharyngeal penetration injuries in dogs. AB - OBJECTIVES: To investigate the correlation between the magnetic resonance imaging findings and subsequent surgical findings for a series of dogs presenting with suspected pharyngeal stick injuries to the Animal Health Trust, Newmarket, between 1995 and 2004. METHODS: Magnetic resonance imaging findings were reviewed for patients undergoing a scan of the pharyngeal or cervical area for suspected foreign bodies during the years 1995 to 2004. RESULTS: Case signalment, history and clinical signs were similar to those reported in previous studies. Magnetic resonance imaging demonstrated foreign material in six of seven cases where this was present. There was good correlation between diagnosis of a foreign body at magnetic resonance imaging and subsequent surgical identification. CLINICAL SIGNIFICANCE: Compared with other imaging modalities, magnetic resonance imaging is very helpful for this type of injury, especially in chronic cases where radiographic evidence of a foreign body is unlikely. It is a valuable aid in the diagnosis of pharyngeal penetration injury and in surgical planning. PMID- 17850278 TI - A study of inherited short tail and taillessness in Pembroke Welsh corgi. AB - OBJECTIVES: To study whether natural short tail in adult Pembroke Welsh corgi is associated with congenital spinal defects. To report anatomical defects in two newborn tailless puppies from short-tailed parents, and to check whether they were homozygous for the dominant mutation in the T-gene (C295G). METHODS: The vertebral column of 19 adult dogs with natural short tail, from short-tail x long tail crossings, was radiographically examined. Two tailless puppies were radiographed and submitted for necropsy. Samples from the puppies, their parents and five siblings were analysed for the mutation of the T-gene. RESULTS: No congenital spinal defects were diagnosed in any of the short-tailed dogs. The tailless puppies had anorectal atresia, had multiple spinal defects and were homozygous for the mutation in the T-gene. CLINICAL SIGNIFICANCE: As tail docking is forbidden in many countries, breeding Pembroke Welsh corgis with natural short tail is becoming increasingly common. Previous studies indicated that the mutation in homozygotes is lethal in early fetal life. It is of clinical significance that natural short tail is probably not associated with congenital spinal defects, as is known from studies of other species, and that homozygotes for this mutation with serious anatomical defects may be born. PMID- 17850279 TI - Ureteral spindle cell sarcoma in a dog. AB - A five-year-old, female spayed Labrador retriever was presented for further investigation of an intra-abdominal mass. Abdominal exploration showed a large mass arising from the right ureter and a ureteronephrectomy was performed. Histopathology of the ureteral mass was consistent with a spindle cell sarcoma. The patient recovered well, but five months later was diagnosed with another tumour, this time in her left abdominal wall. The owners decided not to pursue further treatment and euthanasia was performed a month later. PMID- 17850280 TI - Migration of a Kirschner wire to the heart in a Yorkshire terrier. AB - A 12-year-old, male Yorkshire terrier was presented for acute pulmonary oedema. Thoracic radiographs showed a linear metallic foreign body within the cardiac silhouette. Echocardiogram showed a hyperechoic line extending through the left ventricle, the mitral valve, leading into the left atrium. A 4 cm long Kirschner wire was surgically removed by left fourth thoracotomy. The dog died two days after surgery for acute pulmonary oedema. Necropsy showed thrombi on the mitral leaflets that impeded their movement. PMID- 17850281 TI - Parental investment with a superior alien in the brood. AB - When a parent's parentage differs across breeding attempts, established theory predicts that the parent should invest more in a brood when perceived parentage is high. We present a model of parental investment in which offspring unrelated to the parent have a competitive advantage over the parent's own offspring and take a larger share of investment. We show that this can weaken or, if the competitive advantage is great, reverse the predicted relationship between perceived parentage and parental investment. A moderate competitive advantage of extra-pair young over within-pair young could partly explain the lack of any clear relationship between paternal care and paternity in many studies, and could easily arise if females choose extra-pair partners for good genes. Our results are also relevant to interspecific avian brood parasitism. As parasites reared together with host offspring are often superior competitors, their hosts could benefit from increasing investment in response to suspected parasitism. PMID- 17850282 TI - Important changes in biochemical properties and function of mutated LLP12 domain of HIV-1 gp41. AB - The human immunodeficiency virus type 1 gp41 possesses an unusually long and conserved cytoplasmic region. Mutations in the LLP12 domain in this region have been shown to significantly affect viral competence. It is likely that the impaired infectivity of this mutated virus involves certain biochemical aspects of the peptide LLP12. To test our assumptions, some important biochemical properties and functions of LLP12 domain were studied. The recombinant peptide LLP12 (LLP12 domain on gp41, including LLP1 and LLP2 domains) was prepared via bacterial expression system. Biochemical analysis directly demonstrated its multimeric potential and membrane-binding ability. Several arginine residues in this domain were observed to be extremely highly conserved. Interestingly, the LLP12 mutants constructed by substitution of these arginine residues with alanine (separate mutations in LLP1 or LLP2 or both) showed apparent decreases in their multimeric potential and membrane-binding ability. Comparing our results with independent data on human immunodeficiency virus from other researchers, it appears that both the multimeric state and the membrane affinity of the LLP12 domain of human immunodeficiency virus type 1 gp41 could be involved in viral competence and in the mechanism of human immunodeficiency virus type 1 Env mediated cell fusion. PMID- 17850283 TI - Klippel-Feil syndrome with other associated anomalies in a medieval Portuguese skeleton (13th-15th century). AB - Klippel-Feil syndrome, or synostosis of the cervical spine, is the result of an abnormal division of somites during embryonic development. This report analyses an adult male (exhumed from a Portuguese graveyard dating from the 13th to the 15th century) with malformations in the cranium and vertebral column. Besides the lesions that are typical of Klippel-Feil syndrome type II, other defects usually linked to this pathology are described (occipito-atlantal fusion, hemivertebrae, butterfly vertebrae, cervical rib, changes in normal number of vertebral segments and a possible Sprengel deformity). PMID- 17850284 TI - Immunohistochemical analysis of Sonic hedgehog signalling in normal human urinary tract development. AB - Studies of mouse mutants have demonstrated that Sonic hedgehog (SHH) signalling has a functional role in morphogenesis and differentiation at multiple sites within the forming urinary tract, and urinary tract malformations have been reported in humans with mutations that disrupt SHH signalling. However, there is only strikingly sparse and fragmentary information about the expression of SHH and associated signalling genes in normal human urinary tract development. We used immunohistochemistry to demonstrate that SHH protein was localised in distinct urinary tract epithelia in developing normal humans, in the urothelium of the nascent bladder and in kidney medullary collecting ducts. The expression patterns of the SHH-transducing proteins Patched (PTCH) and Smoothened (SMO) were consistent with long-range paracrine signalling associated with detrusor smooth muscle differentiation in the urogenital sinus. In the developing kidney, SHH and PTCH were expressed in epithelia of the collecting system between 16-26 weeks- surprisingly, SMO was not detected. Analysis of cell proliferation and Cyclin B1 immunohistochemistry at 26 weeks, as compared with a 28 week sample in which SHH expression was down-regulated, was consistent with the idea that SHH and PTCH might influence medullary collecting duct growth by regulating the subcellular localisation of Cyclin B1 independently of SMO. Collectively, these descriptive results generate new hypotheses regarding SHH signal transduction in human urinary tract development and help to explain the varied urinary tract malformation phenotypes noted in individuals with mutations in the SHH pathway. PMID- 17850285 TI - Initial motor axon outgrowth from the developing central nervous system. AB - Rat and chick studies show that the earliest motor rootlet axon bundles emerge from all levels of the neural tube between radial glial end feet which comprise the presumptive glia limitans. The loose arrangement of the end feet at the time of emergence facilitates this passage. The points of emergence are regularly spaced in relation to the long axis of the neural tube and are not defined by any cell contact with its surface. Each rootlet carries a covering of basal lamina from the neural tube surface, which forms a sleeve around it. It is only after bundles of ventral rootlet axons have emerged that cells associate with them, forming clusters on the rootlet surface at a distance peripheral to the CNS surface of both species. A tight collar of glial end feet develops around the axon bundle at the neural tube surface shortly after initial emergence. These arrangements are in sharp contrast to those seen in the sensory rootlets, where clusters of boundary cap cells prefigure the sensory entry zones at the attachments of the prospective dorsal spinal and cranial sensory rootlets. Boundary cap cells resemble cluster cells and a neural crest origin seems the most likely for them. The study clearly demonstrates that no features resembling boundary caps are found in relation to the developing motor exit points. PMID- 17850286 TI - Age estimation in the Mediterranean bottlenose dolphin Tursiops truncatus (Montagu 1821) by bone density of the thoracic limb. AB - The determination of age is an important step in defining the life history traits of individuals and populations. Age determination of odontocetes is mainly based on counting annual growth layer groups in the teeth. However, this useful method is always invasive, requiring the cutting of at least one tooth, and sometimes the results are difficult to interpret. Based on the concept that bone matrix is constantly deposited throughout life, we analysed the bone mineral density of the arm and forearm of a series of bottlenose dolphins (Tursiops truncatus, Montagu 1821) stranded along the Italian coast of the Adriatic Sea or maintained in confined waters. The bone mineral density values we obtained were evaluated as possible age predictors of the Mediterranean population of this species, considering age as determined by counting growth layer groups in sections of the teeth and the total body length of the animal as references. Comparisons between left and right flipper showed no difference. Our results show that bone mineral density values of the thoracic limb are indeed reliable age predictors in Tursiops truncatus. Further investigations in additional odontocete species are necessary to provide strong evidence of the reliability of bone mineral density as an indicator of growth and chronological wear and tear in toothed-whales. PMID- 17850287 TI - Morphologic changes associated with functional adaptation of the navicular bone of horses. AB - Failure of functional adaptation to protect the skeleton from damage is common and is often associated with targeted remodeling of bone microdamage. Horses provide a suitable model for studying loading-related skeletal disease because horses are physically active, their exercise is usually regulated, and adaptive failure of various skeletal sites is common. We performed a histologic study of the navicular bone of three groups of horses: (1) young racing Thoroughbreds (n = 10); (2) young unshod ponies (n = 10); and (3) older horses with navicular syndrome (n = 6). Navicular syndrome is a painful condition that is a common cause of lameness and is associated with extensive remodeling of the navicular bone; a sesamoid bone located within the hoof which articulates with the second and third phalanges dorsally. The following variables were quantified: volumetric bone mineral density; cortical thickness (Ct.Th); bone volume fraction, microcrack surface density; density of osteocytes and empty lacunae; and resorption space density. Birefringence of bone collagen was also determined using circularly polarized light microscopy and disruption of the lacunocanalicular network was examined using confocal microscopy. Remodeling of the navicular bone resulted in formation of transverse secondary osteons orientated in a lateral to medial direction; bone collagen was similarly orientated. In horses with navicular syndrome, remodeling often led to the formation of intracortical cysts and development of multiple tidemarks at the articular surface. These changes were associated with high microcrack surface density, low bone volume fraction, low density of osteocytes, and poor osteocyte connectivity. Empty lacunae were increased in Thoroughbreds. Resorption space density was not increased in horses with navicular syndrome. Taken together, these data suggest that the navicular bone may experience habitual bending across the sagittal plane. Consequences of cumulative cyclic loading in horses with navicular syndrome include arthritic degeneration of adjacent joints and adaptive failure of the navicular bone, with accumulation of microdamage and associated low bone mass, poor osteocyte connectivity, and low osteocyte density, but not formation of greater numbers of resorption spaces. PMID- 17850288 TI - Electrical isolation of the superior vena cava: an adjunctive strategy to pulmonary vein antrum isolation improving the outcome of AF ablation. AB - PV isolation at the antrum (PVAI) has improved safety and efficacy of ablation procedures for atrial fibrillation (AF). AF triggers from the superior vena cava (SVC) may compromise the outcome of PVAI. PURPOSE: We evaluated the (1) incidence of SVC triggers, (2) feasibility of empiric SVC electrical isolation (SVCI) as an adjunct to PVAI, and (3) SVCI safety. METHODS AND RESULTS: Of 190 patients (group I), 24 (12%) showed SVC triggers. Following PVAI, seven patients had AT originating from the SVC and three had AF. After SVCI, all 24 patients were arrhythmia-free 450 +/- 180 days post procedure. In the subsequent 217 patients (group II), empirical SVCI was performed following PVAI. Sixty-six of all 407 patients (16%) experienced recurrence of AF. A repeat procedure in 25 of the 66 patients showed that five (20%) had AF recurrence initiated by SVC triggers, of whom four were among group I patients (4/190; 2%) and one was from group II (1/217; 0.4%), (P < 0.05). Transient diaphragmatic paralysis can be avoided by pacing at the lateral aspect of the SVC using high output (30 mA). There was no SVC stenosis on CT scans before or 3 months after the procedure. There was no sinus node injury. CONCLUSIONS: The SVC harbors the majority of non-PV triggers of AF. SVCI is feasible, safe, and may be considered as an adjunctive strategy to PVAI for ablation of AF. The long-term favorable outcome of this hybrid approach remains to be evaluated in a larger series of patients. PMID- 17850289 TI - Impact of heart rhythm status on registration accuracy of the left atrium for catheter ablation of atrial fibrillation. AB - INTRODUCTION: Registration accuracy is of crucial importance to the successful use of image integration technique to facilitate atrial fibrillation (AF) ablation. It is well known that a patient's heart rhythm can switch from sinus rhythm (SR) to AF or vice versa during an AF ablation procedure. However, the impact of the heart rhythm change on the accuracy of left atrium (LA) registration has not been studied. METHODS: This study included 10 patients who underwent AF ablation. Prior to the ablation procedure, the patients had contrast enhanced cardiac CT scan obtained during SR (n = 7) or AF (n = 3). Using an image integration system (CartoMerge, Biosense Webster Inc.), LA CT surface reconstruction was registered to the real-time mapping space represented by the LA electroanatomic map. To determine the effect of rhythm change on registration accuracy, LA registration was performed during both SR and AF in each study subject. The distance between the surface of the registered LA CT reconstruction and multiple real-time LA electroanatomic map points (surface-to-point distance) was used as an index for LA registration error. The position error after rhythm change was defined as the surface-to-point distance between the surface of the LA CT reconstruction registered in the initial rhythm and the LA electroanatomic map points sampled during the second rhythm. RESULTS: A total of 90 +/- 12 and 92 +/- 9.5 LA electroanatomic map points were sampled for registration during SR and AF, respectively. No significant difference was found in surface-to-point distance when comparing SR with AF as the underlying rhythm during registration (1.91 +/- 0.24 vs 1.84 +/- 0.38 mm, P = 0.60). The position error after rhythm change was not different from the surface-to-point distance of LA registration conducted during the initial rhythm (2.05 +/- 0.39 vs 1.96 +/- 0.29 mm, P = 0.4). The surface-to-point distance did not differ when comparing LA registration conducted during the same versus different rhythm from that during CT imaging (1.96 +/- 0.29 vs 1.79 +/- 0.32 mm, P = 0.13). CONCLUSIONS: Registration error did not differ between LA registrations conducted during the same versus different rhythm as was present during CT imaging. Rhythm changes between SR and AF did not introduce significant error to the LA registration process for catheter ablation of AF. These findings are reassuring and suggest that reregistration is not needed if a patient's rhythm changes from SR to AF or vice versa during an ablation procedure. PMID- 17850290 TI - The heart rate-lowering agent ivabradine inhibits the pacemaker current I(f) in human atrial myocytes. AB - INTRODUCTION: It has been speculated that pacemaker current (I(f)) in human atria could play a role in causing ectopic atrial automaticity. Ivabradine is a novel selective and specific I(f) inhibitor in the sinus node that reduces heart rate without any negative inotropic effect. The aim of the study was to explore possible effects of ivabradine on I(f) in atrial myocytes. METHODS AND RESULTS: Using patch-clamp technique, we studied effects of ivabradine on I(f) present in atrial myocytes isolated from human right appendages of patients undergoing cardiac surgery. The identification of HCN isoforms was obtained by means of multiplex single-cell RT-PCR. Ivabradine induced a marked concentration and use dependent I(f) inhibition with an IC50 at steady state of 2.9 microM. Time constant of block development (Tau(on)) decreases with the increase in the ivabradine concentration. Use-dependent inhibition induced by ivabradine (3 microM) was not modified in the presence of cAMP (10 microM) in the pipette solution. Multiplex single-cell RT-PCR indicates that the major HCN gene subtype detected in atria was HCN2. HCN4 is detected weakly and HCN1 is not significantly detected. CONCLUSIONS: Ivabradine inhibits I(f) current in the nonpacemaker cell with characteristics similar to those described previously in rabbit sinus node cells, but revealed a lesser sensitivity for I(f) recorded in human atrial cell than hHCN4 subunits considered as the major contributors to native f-channels in human sinoatrial node. A potential protection of atrial arrhythmias by ivabradine is discussed. PMID- 17850291 TI - Disruption of parent participation: nurses' strategies to manage parents on children's wards. AB - AIMS AND OBJECTIVES: To investigate parent participation in the hospitalized child's care from the perspectives of children, parents and nurses. BACKGROUND: Parent participation in the hospitalized child's care has been increasingly promoted in paediatric nursing for many years because it ameliorates the adverse aspects of hospitalization, avoids parental separation and contributes to quality care for sick children. Parent participation is assumed to be unproblematic but evidence exists that nurses often have difficulty caring for parents. DESIGN: Using grounded method, data were collected through in-depth interviews, questionnaires and observation with 12 nurses from four paediatric wards in two hospitals in England. RESULTS: The dominant process appeared to be the socialization of parents to their role on the ward through inclusionary and exclusionary tactics. Nurses controlled the nature of parents' participation and parents had to 'toe the line'. Although participation was presented as optional, parents were presented with no course other than acceptance. Parents were expected to stay with their child, behave properly and be involved in care. When parents did not adhere to these norms, they caused disruption to the order and routine of the ward. Compliance or non-compliance to the set of norms and rules was followed by reward or punishment. CONCLUSION: The nurses' dependence on parents' active participation in the organization and delivery of the work suggests that parent participation as it is practised is clearly about administrative efficiency, not consumer empowerment. RELEVANCE TO CLINICAL PRACTICE: Organizational and managerial issues must be examined to ensure that nurses are adequately prepared and resourced to support parents on the ward. Continuing assessment of parents' expectations though a structured assessment tool would help reduce misunderstandings and conflict. Nurses should assess the situational context before relying on subjective impressions and assumptions about parents' participation in care. PMID- 17850292 TI - Exploring the efficacy of a case management model using DOTS in the adherence of patients with pulmonary tuberculosis. AB - AIM: To explore the efficacy of hospitals using case management with Directly Observed Treatment - Short course (DOTS) to monitor the adherence of patients with pulmonary tuberculosis in Taiwan. BACKGROUND: Non-adherence to anti tuberculosis chemotherapy is the major problem in treating patients with tuberculosis. Community-based case management coupled with DOTS has been applied to patients with tuberculosis and has resulted in good results in some countries. Taiwan has a high incidence of tuberculosis, and although it has implemented DOTS, the expected increased efficacy has not yet been realized. DESIGN AND METHODS: The study used a quasi-experimental design. Using age and gender as matching factors, 96 subjects were randomly assigned to one of three groups in 2002-2003. Experimental group I was to receive DOTS case management comprising in hospital education, direct daily observation in the first two months and one home visit per week. Experimental group II received traditional case management comprising in-hospital education and one home visit per month. The control group did not receive any intervention. RESULTS: The adherence, the rate of completion, the treatment success, sputum conversion and chest X-ray improvement of experimental group I were significantly improved compared with experimental group II and the control group. The completion rate in experimental group I was higher than the general rate for Taiwan during the past six years and the treatment success rate met the standards of the World Health Organization. CONCLUSION: Hospitals using case management with DOTS can improve the adherence of tuberculosis patients and the control of tuberculosis-epidemic situations. Relevance to clinical practice. In a rapidly changing healthcare environment, clinical nurses can make a significant contribution to healthcare delivery for tuberculosis patients. This study has provided further insight into the implementation of hospital-to-community level case management using DOTS by nurses. PMID- 17850293 TI - The Chinese Childbirth Self-Efficacy Inventory: the development of a short form. AB - AIMS AND OBJECTIVES: To examine the validity and reliability of the short form of the Childbirth Self-Efficacy Inventory in a clinical Chinese pregnant population. BACKGROUND: Childbirth self-efficacy has become an important psychological construct for both childbirth educators and researchers because pregnant women's perception may influence the meaning and consequences of childbirth. Assessment done by the original Childbirth Self-Efficacy Inventory limits the scientific rigor for generating additional research into the construct, as its items were repetitive and its structure is lengthy. METHODS: This prospective study investigated 293 Chinese pregnant women in their third trimester of pregnancy. The women completed the short form of the Childbirth Self-Efficacy Inventory, the Chinese Self-efficacy Scale and the socio-demographic questionnaire in an interview room of the study hospital. The re-testing of the scale on the participants was carried out two weeks later in the same clinic. RESULTS: Factor analysis and item-subscale correlations supported the conceptual dimensions of the short form of the Chinese Childbirth Self-Efficacy Inventory. The Cronbach's alpha coefficients for both subscales were over 0.9. The convergent validity with the Chinese Self-Efficacy Scale was reflected by a moderate correlation for the two subscales. The efficacy expectancy subscale differentiated primigravid from multigravid women (t = 2.83, P < 0.01, CI = -2.33 to 2.34). CONCLUSIONS: The reliability and validity information presented in this paper supports the use of the short form of the Childbirth Self-Efficacy Inventory as a research instrument in measuring the childbirth self-efficacy among the Chinese population. Further validation of the measure is warranted. RELEVANCE TO CLINICAL PRACTICE: The reliable short form of the Childbirth Self-Efficacy Inventory could be used in routine clinical practice in maternity care services to provide a point of reference for future research and development in both childbirth education and clinical practice. PMID- 17850294 TI - Healthcare and support needs of women with suspected breast cancer. AB - AIM: This paper is a report of a study to investigate changes in the healthcare and support needs during the diagnostic period, and factors that affect these needs in women with suspected breast cancer. BACKGROUND: Although the needs of women with breast cancer are well recognized, few studies have examined the needs of women with suspected breast cancer during the diagnostic period. METHOD: This longitudinal study used an investigator-developed, self-administered questionnaire to collect data from 127 women in Taiwan on three occasions: notification of need for breast biopsy, before biopsy and after diagnosis. The data were collected from November 2004 to April 2005. FINDINGS: Participants had high need levels before and after diagnosis, with their top needs in the domains of healthcare services for diagnosis, follow-up and consultation, and information about the disease. They needed disease- and treatment-related information more than emotional support. Need levels were higher (P < 0.01) before diagnosis than after, highest before biopsy, and lowest after diagnosis. Furthermore, needs were higher (P < 0.01) before than after diagnosis for diagnostic services, disease information, and involvement of family and friends. Higher needs were found in married women with more education and no history of benign tumours. Need level did not differ statistically significantly by age, religious status, degree of social support, family history and breast symptoms. CONCLUSION: Need levels of women with suspected breast cancer vary during the diagnostic period, are highest before breast biopsy, and related to personal characteristics and cultural context. Therefore, during this period, nursing staff should provide patients and families with culturally sensitive, individualized, supportive care. PMID- 17850295 TI - Clinical decision-making skills on the developmental journey from student to Registered Nurse: a longitudinal inquiry. AB - AIM: This paper is a report of a study to explore, from the perspective of nursing students, how they acquire clinical decision-making skills and how well prepared they feel in this respect regarding their responsibilities as Registered Nurses. BACKGROUND: Previous research has focused mainly on exploring experienced nurses' judgement and decision-making. Some studies have elicited senior nursing students' understanding of the process, but none has explored the development of clinical decision-making skills throughout the educational programme and in the first year as a Registered Nurse. METHOD: A volunteer sample of 20 respondents, broadly representative of the student cohort regarding qualifications, age, gender and nursing specialty, was recruited. A longitudinal hermeneutic phenomenological study was carried out from 2000 to 2004, using interviews, reflective journals, care studies, critical incident analyses and document analysis. FINDINGS: Ten conceptions of nursing and 10 perceptions of clinical decision-making were identified and a growing pattern of inter-relationships between them became apparent. A 'matrix model' was developed by cross-referencing the two thematic categories within the timeline of respondents' developmental journey through significant milestones and changing contexts. As Registered Nurses they found having to 'think on your feet' without the 'comfort blanket' of student status both a stressful and formative learning experience. CONCLUSION: Further collaboration between education and health service partners is recommended to integrate clinical decision-making throughout the nursing curriculum, enhance the development of such vital skills, and facilitate the transition from student to Registered Nurse. PMID- 17850296 TI - Consumers' and professionals' perceptions of a breast cancer review clinic. AB - AIM: This paper is a report of a study to explore the healthcare needs of women attending consultant-led breast cancer review clinics from their own perspectives, how these healthcare needs were being met, and healthcare professionals' perceptions of ways in which the service could be delivered more efficiently and effectively. BACKGROUND: The value of routine medical follow-up both in terms of detection of recurrence and patient satisfaction has been questioned. However traditional, where routine follow-up continues, there are rising numbers of women with breast cancer attending review clinics. METHODS: A qualitative approach was adopted, using non-participant observation during seven outpatient oncology/surgical breast review sessions. Interviews were carried out in 2005 with a convenience sample of 21 women clinic attenders, two outpatient nurses, three breast care nurses, four oncologists, three surgeons and an outpatient sister. FINDINGS: Although women saw themselves as having returned to a precancer state, they still had fears of recurrence and a need for reassurance. This need was generally met through the review clinic but many psychosocial needs were unaddressed. However, nurses seemed to be under-used as a potential source of support. Medical and nursing staff perceived that women needed to be reviewed but acknowledged that appropriately prepared nurses could deliver a more holistic and efficient service. CONCLUSION: The number of women with breast cancer requiring ongoing review is likely to increase, but the current review service is not meeting all their needs. A nurse-led follow-up service could be an attractive alternative to routine medical follow-up. PMID- 17850297 TI - Receptor-mediated uptake of Legionella pneumophila by Acanthamoeba castellanii and Naegleria lovaniensis. AB - AIMS: Investigation of the attachment and uptake of Legionella pneumophila by Acanthamoeba castellanii and Naegleria lovaniensis, as these are two critical steps in the subsequent bacterial survival in both amoeba hosts. METHODS AND RESULTS: Initially, the mode of Legionella uptake was examined using inhibitors of microfilament-dependent and receptor-mediated uptake phagocytosis. Secondly, the minimum saccharide structure to interfere with L. pneumophila uptake was determined by means of selected saccharides. Bacterial attachment and uptake by each of the amoeba species occurred through a receptor-mediated endocytosis, which required de novo synthesis of host proteins. Legionella pneumophila showed a high affinity to the alpha1-3D-mannobiose domain of the mannose-binding receptor located on A. castellanii. In contrast, L. pneumophila bacteria had a high affinity for the GalNAcbeta1-4Gal domain of the N-acetyl-D-galactosamine receptor of N. lovaniensis. CONCLUSIONS: Our data pointed to a remarkable adaptation of L. pneumophila to invade different amoeba hosts, as the uptake by both amoeba species is mediated by two different receptor families. SIGNIFICANCE AND IMPACT OF THE STUDY: The fact that L. pneumophila is taken up by two different amoeba species using different receptor families adds further complexity to the host-parasite interaction process, as 14 amoeba species are known to be appropriate Legionella hosts. PMID- 17850298 TI - Penicillium strains as dominant degraders in soil for coffee residue, a biological waste unsuitable for fertilization. AB - AIMS: Coffee residue is an agricultural waste which inhibits the growth of several crops. Therefore coffee residue-degrading microbes in soil were screened, isolated and characterized. METHODS AND RESULTS: Forty isolates were obtained after enrichment culture of soil samples. Seven strains (fast degraders) showed strong degrading activity, while 18 strains (slow degraders) showed weak degrading activity. DNA analysis suggested that the fast degraders are Penicillium, and the slow degraders are Penicillium, Trichoderma/Hypocrea, Fusarium/Gibberella, Phaeoacremonium/Togninia or Acidocella. The all fast degraders are cellulolytic, mannolytic and pectinolytic. CONCLUSIONS: Although it is generally thought that fungi such as Trichoderma contribute largely to aerobic degradation of cellulosic biomass, our data suggested that Penicillium overwhelms them in coffee residue degradation. It was implied that polysaccharides in coffee residue are not degraded independently by different microbes, but degraded simultaneously by strains with cellulolytic, mannolytic and pectinolytic activity. Since there is no report of an ascomycete possessing all the three enzyme activities, the fast degraders are ecologically important and have the potential to be used as producers of the costly enzymes from agricultural wastes. SIGNIFICANCE AND IMPACT OF STUDY: The present results advance our understanding of microbial degradation of a phytotoxic agricultural waste, and offer a new tool for recycling it. PMID- 17850299 TI - Thermus thermophilus TMY isolated from silica scale taken from a geothermal power plant. AB - AIMS: To identify an extreme thermophile, strain TMY, isolated from silica scale from the geothermal electric power plant and to examine microdiversity of Thermus thermophilus strains. MATERIALS AND RESULTS: The isolated strain TMY was identified by morphological, biochemical and physiological tests. Phylogenetic comparison of the strain and other Thermus strains with 16S rDNA analysis, RAPD and ERIC-PCR fingerprinting were performed. Strain TMY was closely related to strain which was isolated from a hot spring in New Zealand and shown to belong to the Japanese Thermus cluster. However, there were considerable genetic differences between strain TMY and other Thermus species using DNA fingerprinting. CONCLUSIONS: Based on morphological, physiological and genetic properties, strain TMY could be a strain of T. thermophilus. The distinct properties of strain TMY suggest that microdiversity of T. thermophilus strains should be considered. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study have demonstrated genetic diversity within T. thermophilus strains, which were previously masked by an almost identical 16S rDNA sequence. RAPD and ERIC PCR could be potential methods for distinguishing between Thermus strains. PMID- 17850300 TI - Thiol redox state and oxidative stress affect sclerotial differentiation of the phytopathogenic fungi Sclerotium rolfsii and Sclerotinia sclerotiorum. AB - AIMS: To investigate the involvement of oxidative stress and thiol redox state (TRS) in sclerotial differentiation of Sclerotium rolfsii and Sclerotinia sclerotiorum. METHODS AND RESULTS: Oxidative stress in these fungi was assessed by lipid peroxidation, which was higher in comparison with their nonsclerotiogenic counterpart strains. TRS [measured as glutathione (GSH) and cysteine] was associated with oxidative stress and differentiation using the TRS modulator and antioxidant Nu-acetylcysteine (AcCSH) and the GSH biosynthesis inducer and inhibitor l-2-oxo-thiazolidine-4-carboxylate and L-buthionine-S,R sulphoximine (BSO) respectively. Differentiation and oxidative stress was decreased by AcCSH in both fungi. The decrease of differentiation by BSO was not associated with oxidative stress in these fungi. CONCLUSIONS: Differentiation and oxidative stress in both fungi depends on the availability of antioxidant noncytotoxic -SH groups and is not depended on any direct antioxidant role of GSH and its precursor cysteine. SIGNIFICANCE AND IMPACT OF THE STUDY: This study helps to understand the mechanism(s) of sclerotial differentiation in these agriculturally important phytopathogenic fungi and proposes that AcCSH can be used as potent fungicide by (i) acting as growth inhibiting cytotoxic oxidant and (ii) sustaining these fungi in their undifferentiated hyphal stage where they are vulnerable to degradation by soil micro-organisms. PMID- 17850301 TI - Genotypic characterization of Enterobacter sakazakii isolates by PFGE, BOX-PCR and sequencing of the fliC gene. AB - AIMS: Enterobacter sakazakii is an emerging food-borne pathogen that can cause rare but severe forms of neonatal meningitis, bacteraemia and necrotizing enterocolitis. A rapid typing method at the strain level is needed to determine the monoclonality or polyclonality of the isolates during outbreaks. METHODS AND RESULTS: The BOX-PCR fingerprinting technique, which targets the repetitive BOX sequences, and sequencing of the flagellin gene, fliC, were evaluated against a panel of 27 Ent. sakazakii strains from clinical and environmental sources. The typeability and discriminatory power of the techniques were compared with those of pulsed-field gel electrophoresis (PFGE), the reference genotyping method. BOX PCR results yielded 92% agreement with PFGE results, whereas fliC gene sequencing was poorly discriminative. CONCLUSIONS: In our study, BOX-PCR and PFGE were similarly discriminatory to type Ent. sakazakii strains. The weak variability of the Ent. sakazakii fliC gene was related to the absence of the variable central domain present in most fliC genes of Enterobacteriaceae. SIGNIFICANCE AND IMPACT OF THE STUDY: The BOX-PCR typing provides an accurate discrimination and a rapid answer to identify clonal isolates of Ent. sakazakii. PMID- 17850302 TI - Antifungal lactic acid bacteria with potential to prolong shelf-life of fresh vegetables. AB - AIM: The aim of this study was to isolate and identify antifungal lactic acid bacteria from fresh vegetables, and evaluate their potential in preventing fungal spoilage of vegetables. METHODS AND RESULTS: Lactic acid bacteria from fresh vegetables were enriched in MRS (de Man Rogosa Sharpe) broth and isolated by plating on MRS agar. All the isolates (359) were screened for activity against Aspergillus flavus of which 10% showed antifungal activity. Potent antifungal isolates were identified by phenotypic characters and confirmed by partial 16S rRNA gene sequencing. These were screened against additional spoilage fungi viz. Fusarium graminearum, Rhizopus stolonifer, Sclerotium oryzae, Rhizoctonia solani, Botrytis cinerea and Sclerotinia minor by overlay method. Most of the isolates inhibited wide range of spoilage fungi. When fresh vegetables were inoculated with either cell suspension (10(4) cells ml(-1)) or cell-free supernatant of Lact. plantarum, followed by application of vegetable spoilage fungi (A. flavus and F. graminearum, R. stolonifer, B. cinerea each with 10(4) conidia ml(-1)) the vegetable spoilage was significantly delayed than control. CONCLUSIONS: Fresh vegetables constitute a good source of lactic acid bacteria with ability to inhibit wide range of spoilage fungi. Such bacteria can be applied to enhance shelf-life of vegetables. In the present study, we report for the first time the antifungal activity of Weissella paramessenteroides and Lact. paracollinoides isolated from fresh vegetables, against wide range of food spoilage fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: Fresh vegetables can be used as a source of antifungal lactic acid bacteria. Their exploitation as biopreservative will help in prolonging shelf-life of fresh vegetables. PMID- 17850303 TI - Validation of growth as measurand for bacterial adhesion to food and feed ingredients. AB - AIMS: A miniaturized adhesion test was designed to study the binding capacity of food and feed ingredients for bacterial cells. METHODS AND RESULTS: Bacteria were allowed to adhere to different fibrous materials supplied as well coatings in microtitration plates. The amount of bacteria retained on the materials was determined in an automated way as growth after addition of liquid medium. The test principle was based on an inverse relationship between initial cell densities and the appearance of growth: The higher adhering cell numbers are, the shorter are the detection times of growth. The growth curves obtained were fitted by nonlinear regression analysis employing a sigmoidal curve model. Growth parameters as (i) the time after incubation at which half of the maximum growth yield was reached; (ii) the time-coordinate of the point of inflection; (iii) the detection time calculated as x-axis intercept of the maximum specific growth rate in the point of inflection; and (iv) the time-coordinate of a growth detection threshold at OD = 0.05 were highly separating for the binding capacity of different food and feed ingredients for bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: With growth as measurand for adhesion, a simple, high-throughput method was developed for the screening of huge numbers of different binding matrices and bacteria. PMID- 17850304 TI - Survival of Listeria innocua on hot and cold beef carcass surfaces. AB - AIMS: This study aimed to determine the survival and growth of Listeria innocua on hot and cold beef carcass surfaces. METHODS AND RESULTS: Four sites, the neck, outside round, brisket and foreshank/brisket, were inoculated with L. innocua (i) immediately after dressing while hot and (ii) when cold after chilling. After inoculation, all carcasses were stored at 4 degrees C for 72 h. Survival of L. innocua on cold surfaces declined during storage and was less than on hot carcasses at all times. Data on the survival of L. innocua in broth (maximum recovery diluent) indicated that counts could not be compared with those on carcasses, in particular on cold carcasses. CONCLUSIONS: The results indicate that L. innocua survives on hot carcass surfaces during chilling, but declines over time on cold surfaces. The decrease in L. innocua counts on cold surfaces may be related to a synergy between the combined stresses of low available water (a(w)) and low temperature. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to determine the effect of chilling on the survival and growth of Listeria on beef carcass surfaces. The information can potentially be used to determine the survival and growth of the pathogen, L. monocytogenes on beef surfaces. PMID- 17850305 TI - A simple multiplex PCR assay for diagnosing virulent Helicobacter pylori infection in human gastric biopsy specimens from subjects with gastric carcinoma and other gastro-duodenal diseases. AB - AIM: To evaluate and develop a multiplex polymerase chain reaction (PCR) assay for diagnosing and specific identification of virulent Helicobacter pylori strains and their main virulence genes cagA, cagE, cagT, vacA and hrgA. METHODS AND RESULTS: Genomic DNA from 82 gastric tissues was screened. A master pool of all the ingredients of multiplex reaction was prepared for amplification. Amplicons were sequenced to confirm the amplification of each target genes. Multiplex PCR assay was able to detect all the five target genes in 81.7% and deletions in one or more loci among 18.3%. Genotype cagT +ve/hrgA +ve/cagA +ve/cagE +ve/vacAs1 +ve was more predominant in this study population (67.07%). hrgA, cagT, cagE and cagA genes were present in 100%, 92.7%, 85.4% and 81.7% of the subjects, respectively. The vacAs1 subtype had higher prevalence frequency in patients with overt gastrointestinal disease (78.57%) than with GERD (gastro esophageal reflux disease) and NUD (non-ulcer dispepsia) (50%). CONCLUSIONS: The multiplex PCR assay developed herein was able to genotype H. pylori isolates based on the main virulence genes. SIGNIFICANCE AND IMPACT OF THE STUDY: The ability to identify H. pylori and the majority of their virulence gene markers by multiplex PCR assay represents a considerable advancement over other PCR-based methods for genotyping H. pylori from large population, and can be explored to gain insights at the genotypic variability exhibited by this pathogen. PMID- 17850306 TI - Patterns of switching phosphodiesterase type 5 inhibitors in the treatment of erectile dysfunction: results from the Erectile Dysfunction Observational Study. AB - AIMS: This report describes patterns of treatment changes with the phosphodiesterase type 5 (PDE5) inhibitors tadalafil, sildenafil and vardenafil, and variables associated with those treatment changes, during the 6-month, prospective, pan-European Erectile Dysfunction Observational Study (EDOS). METHODS: EDOS observed 8047 men > or = 18 years old with erectile dysfunction (ED), who began or changed ED therapy as part of their routine healthcare. Patients could change ED treatment at any time during EDOS. Data were collected at baseline and at 3 (+/- 1) and 6 (+/- 1) months. Analyses included ED treatment naive patients with complete follow-up who were prescribed a PDE5 inhibitor at baseline (n = 4026). RESULTS: Most patients, regardless of what PDE5 inhibitor they were prescribed at baseline, continued on that same PDE5 inhibitor throughout the study. Continuation rates were approximately 89% in the tadalafil cohort, vs. 63-64% in the sildenafil and vardenafil cohorts. The variables most strongly associated with increased risk of switching were prescription of sildenafil or vardenafil, vs. tadalafil, at baseline (odds ratios 4.43 and 4.14 respectively; p < 0.0001). Of patients who switched from tadalafil to another treatment, nearly 25% had switched back to tadalafil by study end. In contrast, of patients who switched from sildenafil or vardenafil, < 10% from each cohort had switched back to their original treatment by study end. CONCLUSION: The data suggest that tadalafil treatment in treatment-naive ED patients may increase their likelihood of treatment continuation. These findings should be interpreted conservatively due to the observational nature of the study. PMID- 17850307 TI - New agents in development for the management of obesity. AB - Obesity is fast becoming the major cause of premature death in the developed world. The rising prevalence of obesity and obesity-related comorbidities also elevates healthcare costs, and reduced quality of life. The National Institute of Clinical Excellence in the UK recommends pharmacotherapy, in conjunction with lifestyle modification, for obese individuals [i.e. body mass index (BMI) of 30 kg/m(2)] and for overweight persons with a BMI greater than 27 kg/m(2), accompanied by at least one comorbidity. However, the current pharmaceutical treatment available to combat this epidemic remains limited. We review the efficacy and pharmacology of the anti-obesity agents currently used in clinical practice as well as some of the potential agents in phase II and III trials. PMID- 17850308 TI - Preoperative smoking cessation: a questionnaire study. AB - BACKGROUND: Preoperative smoking cessation has been shown to improve postoperative outcomes. METHODS: A total of 120 anonymous questionnaires were distributed to non-vascular surgeons practising in four centres in the UK asking about their smoking cessation advice practices, and whether they appreciated both the benefits of preoperative smoking cessation, and the efficacy of smoking cessation interventions. RESULTS: Eighty-three questionnaires were returned (response rate 69%). Twenty-three gastrointestinal surgeons, 11 orthopaedic surgeons, 9 breast surgeons, 12 plastic surgeons, 13 neurosurgeons and 15 urologists took part in this study. Eighty-eight per cent of respondents had not referred any elective patients to smoking cessation services in the previous month. Most non-vascular surgeons underestimated both the benefits of preoperative smoking cessation on outcome, and the efficacy of smoking cessation interventions. CONCLUSIONS: This survey demonstrates that non-vascular surgeons underestimate the fact that preoperative smoking cessation can improve postoperative outcome, and that smoking cessation interventions are successful in helping patients to quit smoking. They largely do not refer patients to smoking cessation services. In order for patients to benefit postoperatively from this intervention it would be necessary to educate surgeons about the scale of the benefit, and the efficacy of smoking cessation interventions or to set up systematic frameworks to offer smoking cessation advice to preoperative patients who smoke. PMID- 17850309 TI - Identification of the agent from Lactobacillus plantarum KFRI464 that enhances bacteriocin production by Leuconostoc citreum GJ7. AB - AIM: To provide evidence that the production of bacteriocin by lactic acid bacteria can be enhanced by the presence of a bacteriocin-sensitive strain and identify the agent that is responsible for enhancing bacteriocin production. METHODS AND RESULTS: One bacteriocin-producing lactic acid bacterium was isolated from kimchi. The strain GJ7 was designated as Leuconostoc citreum GJ7 based on Gram staining, biochemical properties, and 16S rRNA gene sequencing. The isolate produced a heat- and pH-stable bacteriocin (kimchicin GJ7), which has antagonistic activity against a broad spectrum of micro-organisms. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified kimchicin GJ7 showed a single band of molecular weight c. 3500 Da. Cultures of Leuc. citreum GJ7 in the presence of thermally inactivated kimchicin GJ7-sensitive strains, Lactobacillus plantarum KFRI 464, Lactobacillus delbrueckii KFRI 347, or Leuconostoc mesenteroides KCTC 1628, increased bacteriocin production. This inducing factor was characterized and purified from Lact. plantarum KFRI 464, which showed the greatest enhancement of kimchicin GJ7 activity. The inducing factor was purified using a DEAE (diethyl aminoethyl)-Sephacel column and high performance liquid chromatography, and yielded a single band of c. 6500 Da. N terminal sequencing of the inducing factor identified 16 amino acids. The N terminal sequence of the inducing factor was synthesized and examined for the induction of kimchicin GJ7 activity, and was found to induce activity, but at a level about 10% lower than that of the entire molecule. CONCLUSIONS: The presence of a bacteriocin-sensitive strain, Lact. plantarum KFRI 464, acts as an environmental stimulus to activate the production of kimchicin GJ7 by Leuc. citreum GJ7. The inducing factor from Lact. plantarum KFRI 464 is highly homologous to the 30S ribosomal protein S16 from various micro-organisms. The N terminal sequence of the inducing factor examined in this study is a very important sequence related to the inducing activity. Nevertheless, the inducing factor may not be part of the ribosomal protein S16 itself. SIGNIFICANCE AND IMPACT OF THE STUDY: We believe that the present study is the first to identify an agent that is produced by one micro-organism and influences bacteriocin production in another. The bacteriocin-enhancing system described in this study could be effectively used to control the growth of other micro-organisms (sensitive cells) in food systems. Moreover, this enhancement of bacteriocin production can be applied usefully in industrial production of natural food preservatives. PMID- 17850310 TI - Survival kinetics of faecal bacterial indicators in spent broiler litter composting. AB - AIMS: The objective of this study was to deduce and analyse equations that best describe the behaviour of faecal bacterial indicators and two decomposition parameters during broiler litter composting. Mathematical models were fitted and the order of rate equations were identified. METHODS AND RESULTS: The Levenburg Marquardt algorithm was used to fit nonlinear mathematical models to total coliforms (TC), faecal coliforms (FC), Escherichia coli (EC), faecal enterococci (FE), organic-C and volatile solids reduction, VS Red, by the least squares procedure. The rate equations showed that TC, FC and EC reductions were expressed by second-order decay kinetics. FE reduction followed first-order decay. Temperature dependency of decomposition rate was effectively verified by applying empirically derived rate equations. CONCLUSIONS: The governing mathematical models critically compare the inactivation kinetics of faecal indicators. TC, FC and EC were rapidly destroyed while FE was more resistant. Temperature elevation, organic-C and VS Red dynamics provide an accurate understanding of composting induced decomposition of the broiler litter. SIGNIFICANCE AND IMPACT OF THE STUDY: The conservative performance of FE with respect to the other indicators has been established. Hence, FE presents better opportunities to encompass the totality of the composting process in terms of attainment of hygiene efficacy compared with EC. PMID- 17850311 TI - Selection and characterization of aerobic bacteria capable of degrading commercial mixtures of low-ethoxylated nonylphenols. AB - AIMS: Isolation and characterization of new bacterial strains capable of degrading nonylphenol ethoxylates (NPnEO) with a low ethoxylation degree, which are particularly recalcitrant to biodegradation. METHODS AND RESULTS: Seven aerobic bacterial strains were isolated from activated sludges derived from an Italian plant receiving NPnEO-contaminated wastewaters after enrichment with a low-ethoxylated NPnEO mixture. On the basis of 16S rDNA sequence, the strains were positioned into five genera: Ochrobactrum, Castellaniella, Variovorax, Pseudomonas and Psychrobacter. Their degradation capabilities have been evaluated on two commercial mixtures, i.e. Igepal CO-210 and Igepal CO-520, the former rich in low ethoxylated congeners and the latter containing a broader spectrum of NPnEO, and on 4-n-nonylphenol (NP). The strains degraded Igepal CO-210, Igepal CO 520 and 4-n-NP all applied at the initial concentration of 100 mg l(-1), by 35 75%, 35-90% and 15-25%, respectively, after 25 days of incubation. CONCLUSIONS: Some of the isolated strains, in particular the Pseudomonas strains BCb12/1 and BCb12/3, showed interesting degradation capabilities towards low ethoxylated NPnEO congeners maintaining high cell vitality. SIGNIFICANCE AND IMPACT OF THE STUDY: Increased knowledge of bacteria involved in NPnEO degradation and the possibility of using the isolated strains in tailored process for a tertiary biological treatment of effluents of wastewater treatment plants. PMID- 17850312 TI - Response of Wolfiporia cocos to iron availability: alterations in growth, expression of cellular proteins, Fe3+-reducing activity and Fe3+-chelators production. AB - AIMS: The main objective of this study was to evaluate the behaviour of the brown rot fungus Wolfiporia cocos under differential iron availability. METHODS AND RESULTS: W. cocos was grown under three differential iron conditions. Growth, catecholate and hydroxamate production, and mycelial and extracellular Fe3+ reducing activities were determined. Iron starvation slowed fungal growth and accelerated pH decline. Some mycelial proteins of low molecular weight were repressed under iron restriction, whereas others of high molecular weight showed positive iron regulation. Mycelial ferrireductase activity decreased as culture aged, while Fe3+-reducing activity of low molecular reductants constantly increased. Hydroxamates production suffered only limited iron repression, whereas catecholates production showed to be more iron repressible. CONCLUSIONS: W. cocos seems to possess more than one type of iron acquisition mechanism; one involving secretion of organic acids and ferrireductases and/or extracellular reductants, and another relying on secretion of catecholates and hydroxamates chelators. SIGNIFICANCE AND IMPACT OF THE STUDY: This paper is the first to report the kinetic study of brown-rot fungus grown under differential iron availability, and the information provided here contributes to address more traditional problems in protecting wood from brown decay, and also makes a contribution in the general area of the physiology of brown-rot fungi. PMID- 17850313 TI - Formation of diacetyl and acetoin by Lactococcus lactis via aspartate catabolism. AB - AIMS: To verify whether diacetyl can be produced by Lactococcus lactis via amino acid catabolism, and to investigate the impact of the pH on the conversion. METHODS AND RESULTS: Resting cells of L. lactis were incubated in reaction media at different pH values, containing L-aspartic acid or L-alanine as a substrate. After incubation, the amino acid and metabolites were analysed by HPLC and GC/MS. At pH 5 about 75% of aspartic acid and only 40% of alanine was degraded to pyruvate via a transamination step that requires the presence of alpha ketoglutarate in the medium, but diacetyl was only produced from aspartic acid. Three per cent of pyruvate was transformed to acetolactate of which 50% was converted into diacetyl. At pH 5 x 5 and above the pyruvate conversion into acetolactate was less efficient than at pH 5, and acetolactate was mainly decarboxylated to acetoin. CONCLUSIONS: Acetoin and diacetyl can be formed as a result of aspartate or alanine catabolism by L. lactis in the presence of alpha ketoglutarate in the medium. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactic acid bacteria exhibiting both glutamate dehydrogenase activity and high aspartate aminotransferase activity are expected to be good diacetyl producers during cheese ripening at pH close to 5. PMID- 17850314 TI - Cd (II) stress response during the growth of Aspergillus niger B 77. AB - AIMS: To investigate the relationship between growth, heavy metal ions uptake and participation of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the protection of Aspergillus niger B 77 against cadmium stress. METHODS AND RESULTS: The stress response of the model fungal strain, under conditions of a wide range of Cd (II) ion concentrations, was investigated by determining the biomass formation, protein biosynthesis, SOD and CAT activities and heavy metal uptake in growing cells. Exposure to heavy metal ions induced an increase in protein content, heavy metal uptake and SOD activity, and a heavy decrease in CAT activity. CONCLUSION: The results obtained indicated that the tolerance of A. niger to Cd (II) was correlated with the heavy metal uptake, reactive oxygen species generation in the cells and the efficiency of antioxidative defence system. SIGNIFICANCE AND IMPACT OF THE STUDY: Evidence is provided for the possibility that oxidative stress plays a major role in the effect of Cd (II) ions on A. niger. These data could offer useful information when creating new strategies and methodological improvements for bioremediation with the participation of fungi. PMID- 17850315 TI - Changes in the properties of Bacillus thuringiensis after prolonged culture in a rich medium. AB - AIM: To investigate the effect of repeated culture in a rich medium on certain genetic, metabolic, pathogenic and structural characteristics of fresh isolates of Bacillus thuringiensis. METHODS AND RESULTS: Four strains of B. thuringiensis, which had been isolated in vegetative form from leaf surfaces, were grown for 500 generations in batch culture in a rich medium. One of the strains, S4g, differed from the parent in the following respects: greater cell width; changed plasmid profile; complete loss of ability to produce delta-endotoxins; loss of ability to produce beta-exotoxin and disruption of vip3 gene; radically different fatty acid composition; and altered metabolic activity. Two of the other evolved strains (S1g and S6g) showed differences in fatty acid profiles compared with the parents. Genetic finger-printing showed that there were also mutations in the cry genes of two of the evolved strains (S1g and S2g). The delta-endotoxins of strain S6g were significantly less toxic to the larvae of Pieris brassica compared with those of the parent and it also differed in the plasmid content. CONCLUSION: Radical and unpredictable changes can occur in fresh isolates of B. thuringiensis when subjected to growth in the laboratory. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first analysis of a Gram positive and biotechnologically significant bacterium after repeated laboratory culture. It is of great relevance to the biotechnological exploitation of B. thuringiensis that prolonged growth of environmental isolates on laboratory culture media can have profound effects on their structure, genome and virulence determinants. PMID- 17850316 TI - A comparison of molecular typing methods for Moraxella catarrhalis. AB - AIMS: Three molecular typing techniques were examined to determine which method was the most discriminatory in order to perform epidemiological typing of Moraxella catarrhalis. METHODS AND RESULTS: Twenty-five Mor. catarrhalis isolates obtained from nasopharyngeal aspirates collected from Aboriginal and non Aboriginal children were subjected to random amplified polymorphic DNA (RAPD) analysis, automated ribotyping and pulsed field gel electrophoresis (PFGE). RAPD analysis determined two Mor. catarrhalis types, automated ribotyping with PstI determined four Mor. catarrhalis ribogroups and PFGE analysis with NotI determined 21 pulse field groups within the 25 isolates examined. CONCLUSIONS: Analysis of discrimination index and typeability demonstrated that PFGE is the most discriminatory method for typing Mor. catarrhalis. SIGNIFICANCE AND IMPACT OF THE STUDY: This study confirms that PFGE is the most appropriate molecular tool for the epidemiological study of Mor. catarrhalis. PMID- 17850317 TI - Characterization of antimicrobial susceptibility and virulence genes of Salmonella serovars collected at a commercial turkey processing plant. AB - AIMS: To determine the antimicrobial susceptibility profiles, distribution of class 1 integrons, virulence genes and genes encoding resistance to tetracycline (tetA, tetC, tetD and tetE) and streptomycin (strA, strB and aadA1) in Salmonella recovered from turkeys. METHODS AND RESULTS: The antimicrobial susceptibility of 80 isolates was determined using National Antimicrobial Resistance Monitoring System. The distribution of resistance genes, class 1 integrons and virulence genes was determined using PCR. Resistances to tetracycline (76 x 3%) and streptomycin (40%) were common. Sixty-two (77 x 5%) isolates displayed resistance against one or more antimicrobials and 33 were multi-drug resistant. tetA was detected in 72 x 5% of the isolates, while tetC, tetD and tetE were not detected. The strA and strB genes were detected in 73 x 8% of the isolates. Two isolates possessed class 1 integrons of 1 kb in size, containing the aadA1 gene conferring resistance to streptomycin and spectinomycin. Fourteen of the virulence genes were detected in over 80% of the isolates. CONCLUSIONS: This study shows that continuous use of tetracycline and streptomycin in poultry production selects for resistant strains. The Salmonella isolates recovered possess significant ability to cause human illness. SIGNIFICANCE AND IMPACT OF THE STUDY: Information from this study can be employed in guiding future strategies for the use of antimicrobials in poultry production. PMID- 17850318 TI - Diversity analysis of antagonists from rice-associated bacteria and their application in biocontrol of rice diseases. AB - AIMS: To understand the diversity, taxonomy and antagonistic potential of rice associated bacteria, and to discover new bacteria for biocontrol of rice foliar pathogens. METHODS AND RESULTS: Amplified ribosomal DNA restriction analysis (ARDRA), BOX-PCR and 16S rRNA gene sequence analysis were used to identify the diversity of 203 rice-associated antagonistic bacteria. Eleven potential biocontrol bacteria were used to test their biological control of rice blast in a natural field experiment. Eleven different genera were encountered in five divisions, including Bacilli, Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria and Deinococci. The most prominent genus in all microenvironments was Bacillus (68 x 5%). The efficacy of rice leaf blast biocontrol was 64 x 35% for strain 1Pe2, 57 x 86% for strain 2R37 and 56 x 44% for strain 1Re14. CONCLUSIONS: Biocontrol data from the field experiments demonstrated no positive correlation between antagonism, physiological characteristics and biocontrol efficacy. There was significant diversity among the rice-associated bacteria isolated from different microenvironments. The most prominent genus of all microenvironments was Bacillus. Brevibacillus brevis strain 1Pe2 and Deinococcus aquaticus strain 1Re14 have good potential for field application and commercial use. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first attempt to study the diversity and identification of rice-associated antagonistic bacteria from different microenvironments, and endophytic bacteria Deinococcus aquaticus strain 1Re14, Acidovorax sp. isolate 3Re21 and Brevibacillus brevis strain 1Pe2 are first reported as rice-associated bacteria. PMID- 17850319 TI - Effect of physical, chemical and environmental characteristics on arbuscular mycorrhizal fungi in Brachiaria decumbens (Stapf) pastures. AB - AIM: To evaluate the effects of soil physical and chemical factors (pH, conductivity, humidity, available phosphorus and organic matter) and environmental factors (temperature, relative air humidity, altitude and atmospheric pressure) on arbuscular mycorrhizal fungi (AMF)-Brachiaria decumbens grass relationship. Furthermore to establish patterns of microbiological responses that allow to differentiate the study sites in two relief types. METHODS AND RESULTS: Mycorrhizal characteristics (spore density, external hyphae and root colonizations by hyphae, vesicles and arbuscules), physical and chemical factors in soil and environmental factors were measured. CONCLUSIONS: The effect of physical, chemical and environmental factors on microbiological variables was related to the type of relief 'valley and hilly terrain'; the AMF behaviour was affected only over narrower ranges of evaluated variables. Similarly, the colonization of B. decumbens roots by AMF hyphae, vesicles and the mycorrhizal spore density follow different patterns according to the relief type. SIGNIFICANCE AND IMPACT OF THE STUDY: The type of relief is one of the factors to be taken into consideration to evaluate the AMF inoculum and root colonization of these pastures, because of the influence of slope - as physical property of soil on AMF. PMID- 17850320 TI - Persistence of Shiga toxin-producing Escherichia coli O26 in various manure amended soil types. AB - AIMS: To evaluate the behaviour of Shiga toxin-producing Escherichia coli (STEC) O26 strains inoculated in manure-amended soils under in vitro conditions. METHODS AND RESULTS: Four green fluorescent protein (GFP)-labelled STEC O26 strains were inoculated in duplicate (at 10(6) CFU g(-1)) in three different manure-amended soil types, including two loam soils (A and B) and one clay loam soil (C), and two incubation temperatures (4 and 20 degrees C) were tested. STEC counts and soil physical parameters were periodically monitored. STEC O26 cells were able to persist during extended periods in soil even in the presence of low moisture levels, i.e. less than 0 x 08 g H2O g(-1) dry soil. At 4 and 20 degrees C, STEC could be detected in soil A for 288 and 196 days, respectively, and in soils B and C for at least 365 days postinoculation at both temperatures. The ambient temperature (i.e. 20 degrees C) was significantly associated with the highest STEC count decline in all soils tested. CONCLUSIONS: The temperature and soil properties appear to be contributory factors affecting the long-term survival of STEC O26 in manure-amended soils. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides useful information regarding the ecology of STEC O26 in manure amended soils and may have implications for land and waste management. PMID- 17850321 TI - Protective effect of hop beta-acids on microbial degradation of thick juice during storage. AB - AIMS: This study assessed the value of a commercial alkaline solution of hop beta acids (HBA) for prevention of microbial degradation of thick juice, a concentrated intermediate product in the production of beet sugar. METHODS AND RESULTS: The antimicrobial effect of different concentrations of HBA against microbial degradation of thick juice was tested in a pilot-scale storage experiment. Chemical, biochemical and microbial parameters were monitored during thick juice storage. Thick juice degradation, indicated as a decrease in pH, was generally accompanied by an increase in the count of fastidious bacteria (FB) on Columbia Agar with Sheep Blood (CAwSB), which were mainly identified as Tetragenococcus halophilus. Addition of HBA delayed juice acidification and the development of FB in a concentration-dependent manner. The susceptibility of FB to HBA was determined by plating degraded thick juice (FB > 10(5) CFU ml(-1) on CAwSB plates with different concentrations of HBA (0-160 ppm). None of the HBA concentrations tested reduced the number of FB colonies formed, but increasing HBA concentrations extended the lag time of colony formation. CONCLUSIONS: HBA produce no measurable bactericidal effect, but retard the development of FB in thick juice. Moreover, HBA do not prevent the thick juice from deteriorating, but significantly delay its degradation. SIGNIFICANCE AND IMPACT OF THE STUDY: These results indicate that adding a commercially available HBA formulation can prolong the storage life of thick juice in the sugar industry, although degradation cannot be eliminated. Future research will focus on the detailed characterization of FB consistently isolated from degraded thick juice and on determining their role in thick juice degradation. PMID- 17850322 TI - Cost-effectiveness of raising HDL cholesterol by adding prolonged-release nicotinic acid to statin therapy in the secondary prevention setting: a French perspective. AB - AIM: To evaluate the cost-effectiveness of raising high-density lipoprotein cholesterol (HDL-C) with add-on nicotinic acid in statin-treated patients with coronary heart disease (CHD) and low HDL-C, from the French healthcare system perspective. METHODS AND RESULTS: Computer simulation economic modelling incorporating two decision analytic submodels was used. The first submodel generated a cohort of 2000 patients and simulated lipid changes using baseline characteristics and treatment effects from the ARterial Biology for the Investigation of the Treatment Effects of Reducing cholesterol (ARBITER 2) study. Prolonged-release (PR) nicotinic acid (1 g/day) was added in patients with HDL-C < 40 mg/dl (1.03 mmol/l) on statin alone. The second submodel used standard Markov techniques to evaluate long-term clinical and economic outcomes based on Framingham risk estimates. Direct medical costs were accounted from a third party payer perspective [2004 Euros (euro)] and discounted by 3%. Addition of PR nicotinic acid to statin therapy resulted in substantial health gain and increased life expectancy, at a cost well within the threshold (< 50,000 euros per life year gained) considered good value for money in Western Europe. CONCLUSIONS: Raising HDL-C by adding PR nicotinic acid to statin therapy in CHD patients was cost-effective in France at a level considered to represent good value for money by reimbursement authorities in Europe. This strategy was highly cost-effective in CHD patients with type 2 diabetes. PMID- 17850324 TI - Generic products of antiepileptic drugs (AEDs): is it an issue? AB - The availability of generic products of antiepileptic drugs (AEDs) has raised the following concerns: (1) Do generic AEDs work as well as brand AEDs in terms of their efficacy, safety and quality? (2) Can generic AEDs be used as substitutions for brand AEDs? and (3) Can generic products of AEDs be used interchangeably? The traditional average bioequivalence analysis addresses concern 1 but does not provide a complete adequate response to concerns 2 and 3. Drug interchangeability can be classified as drug prescribability or drug switchability. Drug prescribability refers to the situation where a patient is treated for the first time so that either a brand or a bioequivalent generic AED can be chosen. Drug switchability refers to the situation in which a brand AED is switched to a bioequivalent generic product of the same AED. The traditional average bioequivalence approach is sufficient to evaluate the prescribability of generic products, but does not ensure the switchability between prescribable formulations. The necessity of assuring switchability of two formulations can be addressed by individual bioequivalence. While the switch to generic AEDs is well tolerated by many patients and in general cost-effective, seizure control should not be sacrificed on the basis of cost alone, as the major end point in treating epilepsy with AEDs is seizure control without side effects. Until we have individual (within patient) bioequivalence data on generic AEDs and/or the tools to a priori identify the subset of patients susceptible to the generic switch, a switch of AED products in seizure-free patients is not recommended. PMID- 17850325 TI - The economics of haemophilia prophylaxis: governmental and insurer perspectives. Proceedings of the Second International Prophylaxis Study Group (IPSG) symposium. PMID- 17850323 TI - High risk of reading disability and speech sound disorder in rolandic epilepsy families: case-control study. AB - PURPOSE: Associations between rolandic epilepsy (RE) with reading disability (RD) and speech sound disorder (SSD) have not been tested in a controlled study. We conducted a case-control study to determine whether (1) RD and SSD odds are higher in RE probands than controls and (2) an RE proband predicts a family member with RD or SSD, hence suggesting a shared genetic etiology for RE, RD, and SSD. METHODS: Unmatched case-control study with 55 stringently defined RE cases, 150 controls in the same age range lacking a primary brain disorder diagnosis, and their siblings and parents. Odds ratios (OR) were calculated by multiple logistic regression, adjusted for sex and age, and for relatives, also adjusted for comorbidity of RD and SSD in the proband. RESULTS: RD was strongly associated with RE after adjustment for sex and age: OR 5.78 (95% CI: 2.86-11.69). An RE proband predicts RD in family members: OR 2.84 (95% CI: 1.38-5.84), but not independently of the RE proband's RD status: OR 1.30 (95% CI: 0.55-12.79). SSD was also comorbid with RE: adjusted OR 2.47 (95%CI: 1.22-4.97). An RE proband predicts SSD in relatives, even after controlling for sex, age and proband SSD comorbidity: OR 4.44 (95% CI: 1.93-10.22). CONCLUSIONS: RE is strongly comorbid with RD and SSD. Both RD and SSD are likely to be genetically influenced and may contribute to the complex genetic etiology of the RE syndrome. Siblings of RE patients are at high risk of RD and SSD and both RE patients and their younger siblings should be screened early. PMID- 17850326 TI - Identification of genes differentially expressed in the phytopathogenic fungus Cercospora nicotianae between cercosporin toxin-resistant and -susceptible strains. AB - Plant pathogens from the genus Cercospora produce cercosporin, a photoactivated fungal toxin that generates toxic reactive oxygen species. Mechanisms governing toxin auto-resistance in Cercospora spp. are poorly understood. In this work, suppressive subtractive hybridization was used to identify genes differentially expressed between the cercosporin-resistant wild-type (WT) Cercospora nicotianae and a sensitive strain lacking a transcription factor (CRG1) that regulates resistance. Out of 338 sequences recovered, 185 unique expressed sequence tags (ESTs) were obtained and classified into functional categories. The majority of genes showed predicted expression differences, and 38.5% were differentially expressed at least twofold between the WT and mutant strain. ESTs were recovered with homology to genes involved in detoxification of noxious compounds, multidrug membrane transporters and antioxidant and polyketide biosynthetic enzymes as well as to ATPases and ATP synthases. The findings suggest that CRG1 regulates genes involved in pH responses in addition to those involved in toxin resistance and biosynthesis. PMID- 17850327 TI - Coprinellus curtus (Hitoyo-take) prevents diseases of vegetables caused by pathogenic fungi. AB - A strain of Coprinellus curtus (designated GM-21), a basidiomycete that suppressed bottom-rot disease of Chinese cabbage, 'pak-choi' (Brassica campestris), caused by the pathogen Rhizoctonia solani Pak-choi 2 was isolated. The mechanism of plant disease suppression was discovered to be hyphal interference, a combative fungal interaction between strain GM-21 and the pathogen. The antifungal spectrum of strain GM-21 was shown to include R. solani and Fusarium sp., i.e. strain GM-21 showed disease-suppressive ability against bottom-rot disease of lettuce and Rhizoctonia-patch disease of mascarene grass caused by strains of R. solani. In addition, clear evidence of hyphal interference between strain GM-21 and Fusarium pathogens that cause crown (foot) and root-rot disease of tomato and Fusarium wilt of melon, respectively, was demonstrated. It was thus considered that GM-21 is effective for suppressing soil borne pathogens, and that GM-21 presents new possibilities for biological control of vegetable diseases. PMID- 17850328 TI - Construction and preliminary analysis of a metagenomic library from a deep-sea sediment of east Pacific Nodule Province. AB - The Pacific Nodule Province is a unique ocean area containing an abundance of polymetallic nodules. To explore more genetic information and discover potentially industrial useful genes of the microbial community from this particular area, a cosmid library with an average insert of about 35 kb was constructed from the deep-sea sediment. The bacteria in the cosmid library were composed mainly of Proteobacteria including Alphaproteobacteria, Gammaproteobacteria and Deltaproteobacteria. The end sequences of some cosmid clones were determined and the complete insert sequences of two cosmid clones, 10D02 and 17H9, are presented. 10D02 has a length of 40.8 kb and contains 40 predicted encoding genes. It contains a partial 16S rRNA gene of Alphaproteobacteria. 17H9 is 36.8 kb and predicted to have 31 encoding genes and a 16S-23S-5S rRNA gene operon. Phylogenetic analysis of 16S and 23S rRNA gene sequence on the 17H9 both reveals that the inserted DNA from 17H9 came from a novel Alphaproteobacteria and is closely related to Magnetospirillum species. The predicted proteins of ORF 1-11 also have high identity to those of Magnetospirillum species, and the organization of these genes is highly conserved among known Magnetospirillum species. The data suggest that the retrieved DNA in 17H9 might be derived from a novel Magnetospirillum species. PMID- 17850329 TI - Genotypic distribution of an indigenous model microorganism along an estuarine gradient. AB - Using the genus Desulfobulbus as an indigenous model, microbial distribution along an estuarine gradient was investigated. Denaturing gradient gel electrophoresis analysis indicated a sequential change in Desulfobulbus genotypes along the estuary with marine, brackish and freshwater genotypes detected. This differential distribution was significantly correlated with porewater concentrations of chloride, sulphate and nitrate. Temporal analysis indicated that there was a shift in the whole Desulfobulbus community towards to marine end of the estuary by the end of the winter compared with the late summer. This distribution pattern is similar to those seen with other estuarine organisms and, given the correlation with chloride and sulphate, is indicative of classic niche separation within this genus driven by gross environmental factors such as salinity. These results will help in developing a truly ecological description of microbial biodiversity. PMID- 17850331 TI - The heat shock protein 70 molecular chaperone network in the pancreatic endoplasmic reticulum - a quantitative approach. AB - Traditionally, the canine pancreatic endoplasmic reticulum (ER) has been the workhorse for cell-free studies on protein transport into the mammalian ER. These studies have revealed multiple roles for the major ER-luminal heat shock protein (Hsp) 70, IgG heavy chain-binding protein (BiP), at least one of which also involves the second ER-luminal Hsp70, glucose-regulated protein (Grp) 170. In addition, at least one of these BiP activities depends on Hsp40. Up to now, five Hsp40s and two nucleotide exchange factors, Sil1 and Grp170, have been identified in the ER of different mammalian cell types. Here we quantified the various proteins of this chaperone network in canine pancreatic rough microsomes. We also characterized the various purified proteins with respect to their affinities for BiP and their effect on the ATPase activity of BiP. The results identify Grp170 as the major nucleotide exchange factor for BiP, and the resident ER-membrane proteins ER-resident J-domain protein 1 plus ER-resident J-domain protein 2/Sec63 as prime candidates for cochaperones of BiP in protein transport in the pancreatic ER. Thus, these data represent a comprehensive analysis of the BiP chaperone network that was recently linked to two human inherited diseases, polycystic liver disease and Marinesco-Sjogren syndrome. PMID- 17850332 TI - Probing the determinants of coenzyme specificity in Peptostreptococcus asaccharolyticus glutamate dehydrogenase by site-directed mutagenesis. AB - Glutamate dehydrogenase (EC 1.4.1.2-4) from Peptostreptococcus asaccharolyticus has a strong preference for NADH over NADPH as a coenzyme, over 1000-fold in terms of kcat/Km values. Sequence alignments across the wider family of NAD(P) dependent dehydrogenases might suggest that this preference is mainly due to a negatively charged glutamate at position 243 (E243) in the adenine ribose-binding pocket. We have examined the possibility of altering coenzyme specificity of the Peptostreptococcus enzyme, and, more specifically, the role of residue 243 and neighbouring residues in coenzyme binding, by introducing a range of point mutations. Glutamate dehydrogenases are unusual among dehydrogenases in that NADPH-specific forms usually have aspartate at this position. However, replacement of E243 with aspartate led to only a nine-fold relaxation of the strong discrimination against NADPH. By contrast, replacement with a more positively charged lysine or arginine, as found in NADPH-dependent members of other dehydrogenase families, allows a more than 1000-fold shift toward NADPH, resulting in enzymes equally efficient with NADH or NADPH. Smaller shifts in the same direction were also observed in enzymes where a neighboring tryptophan, W244, was replaced by a smaller alanine (approximately six-fold) or Asp245 was changed to lysine (32-fold). Coenzyme binding studies confirm that the mutations result in the expected major changes in relative affinities for NADH and NADPH, and pH studies indicate that improved affinity for the extra phosphate of NADPH is the predominant reason for the increased catalytic efficiency with this coenzyme. The marked difference between the results of replacing E243 with aspartate and with positive residues implies that the mode of NADPH binding in naturally occurring NADPH-dependent glutamate dehydrogenases differs from that adopted in E243K or E243D and in other dehydrogenases. PMID- 17850333 TI - Receptor- and calcium-dependent induced inositol 1,4,5-trisphosphate increases in PC12h cells as shown by fluorescence resonance energy transfer imaging. AB - The production and further metabolism of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] require several calcium-dependent enzymes, but little is known about subsequent calcium-dependent changes in cellular Ins(1,4,5)P3. To study the calcium dependence of muscarinic acetylcholine receptor-induced Ins(1,4,5)P3 increases in PC12h cells, we utilized an Ins(1,4,5)P3 imaging system based on fluorescence resonance energy transfer and using green fluorescent protein variants fused with the pleckstrin homology domain of phospholipase C-delta1. The intracellular calcium concentration, monitored by calcium imaging, was adjusted by thapsigargin pretreatment or alterations in extracellular calcium concentration, enabling rapid receptor-independent changes in calcium concentration via store-operated calcium influx. We found that Ins(1,4,5)P3 production was increased by a combination of receptor- and calcium-dependent components, rather than by calcium alone. The level of Ins(1,4,5)P3 induced by the receptor was found to be half that induced by the combined receptor and calcium components. Increases in calcium levels prior to receptor activation did not affect the subsequent receptor-induced Ins(1,4,5)P3 increase, indicating that calcium does not influence Ins(1,4,5)P3 production without receptor activation. Removal of both the receptor agonists and calcium rapidly restored calcium and Ins(1,4,5)P3 levels, whereas removal of calcium alone restored calcium to its basal concentration. Similar calcium-dependent increases in Ins(1,4,5)P3 were also observed in Chinese hamster ovary cells expressing m1 muscarinic acetylcholine receptor, indicating that the observed calcium dependence is common to Ins(1,4,5)P3 production. To our knowledge, our results are the first showing receptor- and calcium-dependent components within cellular Ins(1,4,5)P3. PMID- 17850334 TI - Variation in gene content among geographically diverse Sulfolobus isolates. AB - The ability of competitive (i.e., comparative) genomic hybridization (CGH) to assess similarity across entire microbial genomes suggests that it should reveal diversification within and between natural populations of free-living prokaryotes. We used CGH to measure relatedness of genomes drawn from Sulfolobus populations that had been shown in a previous study to be diversified along geographical lines. Eight isolates representing a wide range of spatial separation were compared with respect to gene-specific tags based on a closely related reference strain (Sulfolobus solfataricus P2). For the purpose of assessing genetic divergence, 232 loci identified as polymorphic were assigned one of two alleles based on the corresponding fluorescence intensities from the arrays. Clustering of these binary genotypes was stable with respect to changes in the threshold and similarity criteria, and most of the groupings were consistent with an isolation-by-distance model of diversification. These results indicate that increasing spatial separation of geothermal sites correlates not only with minor sequence polymorphisms in conserved genes of Sulfolobus (demonstrated in the previous study), but also with the regions of difference (RDs) that occur between genomes of conspecifics. In view of the abundance of RDs in prokaryotic genomes and the relevance that some RDs may have for ecological adaptation, the results further suggest that CGH on microarrays may have advantages for investigating patterns of diversification in other free-living archaea and bacteria. PMID- 17850335 TI - Grinnellian and Eltonian niches and geographic distributions of species. AB - In the recent past, availability of large data sets of species presences has increased by orders of magnitude. This, together with developments in geographical information systems and statistical methods, has enabled scientists to calculate, for thousands of species, the environmental conditions of their distributional areas. The profiles thus obtained are obviously related to niche concepts in the Grinnell tradition, and separated from those in Elton's tradition. I argue that it is useful to define Grinnellian and Eltonian niches on the basis of the types of variables used to calculate them, the natural spatial scale at which they can be measured, and the dispersal of the individuals over the environment. I use set theory notation and analogies derived from population ecology theory to obtain formal definitions of areas of distribution and several types of niches. This brings clarity to several practical and fundamental questions in macroecology and biogeography. PMID- 17850336 TI - Sanio's laws revisited. Size-dependent changes in the xylem architecture of trees. AB - Early observations led Sanio [Wissen. Bot., 8, (1872) 401] to state that xylem conduit diameters and lengths in a coniferous tree increase from the apex down to a height below which they begin to decrease towards the tree base. Sanio's law of vertical tapering has been repeatedly tested with contradictory results and the debate over the scaling of conduit diameters with distance from the apex has not been settled. The debate has recently acquired new vigour, as an accurate knowledge of the vertical changes in wood anatomy has been shown to be crucial to scaling metabolic properties to plant and ecosystem levels. Contrary to Sanio's hypothesis, a well known model (MST, metabolic scaling theory) assumes that xylem conduits monotonically increase in diameter with distance from the apex following a power law. This has been proposed to explain the three-fourth power scaling between size and metabolism seen across plants. Here, we (i) summarized available data on conduit tapering in trees and (ii) propose a new numerical model that could explain the observed patterns. Data from 101 datasets grouped into 48 independent profiles supported the notions that phylogenetic group (angiosperms versus gymnosperms) and tree size strongly affected the vertical tapering of conduit diameter. For both angiosperms and gymnosperms, within-tree tapering also varied with distance from the apex. The model (based on the concept that optimal conduit tapering occurs when the difference between photosynthetic gains and wall construction costs is maximal) successfully predicted all three major empirical patterns. Our results are consistent with Sanio's law only for large trees and reject the MST assumptions that vertical tapering in conduit diameter is universal and independent of rank number. PMID- 17850337 TI - Phylogenetic concordance analysis shows an emerging pathogen is novel and endemic. AB - Distinguishing whether pathogens are novel or endemic is critical for controlling emerging infectious diseases, an increasing threat to wildlife and human health. To test the endemic vs. novel pathogen hypothesis, we present a unique analysis of intraspecific host-pathogen phylogenetic concordance of tiger salamanders and an emerging Ranavirus throughout Western North America. There is significant non concordance of host and virus gene trees, suggesting pathogen novelty. However, non-concordance has likely resulted from virus introductions by human movement of infected salamanders. When human-associated viral introductions are excluded, host and virus gene trees are identical, strongly supporting coevolution and endemism. A laboratory experiment showed an introduced virus strain is significantly more virulent than endemic strains, likely due to artificial selection for high virulence. Thus, our analysis of intraspecific phylogenetic concordance revealed that human introduction of viruses is the mechanism underlying tree non-concordance and possibly disease emergence via artificial selection. PMID- 17850338 TI - Anthrax lethal toxin-induced inflammasome formation and caspase-1 activation are late events dependent on ion fluxes and the proteasome. AB - Anthrax lethal toxin (LT) is cytotoxic to macrophages from certain inbred mouse strains. The gene controlling macrophage susceptibility to LT is Nalp1b. Nalp1b forms part of the inflammasome, a multiprotein complex involved in caspase-1 activation and release of interleukin (IL)-1beta and IL-18. We confirm the role of caspase-1 in LT-mediated death by showing that caspase inhibitors differentially protected cells against LT, with the degree of protection corresponding to each compound's ability to inhibit caspase-1. Caspase-1 activation and cytokine processing and release were late events inhibited by elevated levels of KCl and sucrose, by potassium channel blockers, and by proteasome inhibitors, suggesting that inflammasome formation requires a protein degradation event and occurs downstream of LT-mediated potassium efflux. In addition, IL-18 and IL-1beta release was dependent on cell death, indicating that caspase-1-mediated cytotoxicity is independent of these cytokines. Finally, inducing NALP3-inflammasome formation in LT-resistant macrophages did not sensitize cells to LT, suggesting that general caspase-1 activation cannot account for sensitivity to LT and that a Nalp1b-mediated event is specifically required for death. Our data indicate that inflammasome formation is a contributing, but not initiating, event in LT-mediated cytotoxicity and that earlier LT-mediated events leading to ion fluxes are required for death. PMID- 17850339 TI - Eleven novel OXA-51-like enzymes from clinical isolates of Acinetobacter baumannii. PMID- 17850340 TI - Clinical epidemiology of ciprofloxacin-resistant Proteus mirabilis isolated from urine samples of hospitalised patients. AB - This study investigated the clinical characteristics of ciprofloxacin-resistant Proteus mirabilis isolates from urine samples associated with nosocomial infection or colonisation, and identified the risk-factors for ciprofloxacin resistance. Data for patients with ciprofloxacin-resistant P. mirabilis isolates (n=13) were compared with those for randomly selected patients with ciprofloxacin susceptible P. mirabilis isolates (n=40) who were matched by temporal occurrence as control patients. The majority of ciprofloxacin-resistant P. mirabilis isolates were multiresistant, and ciprofloxacin resistance was associated significantly with previous use of fluoroquinolones and production of extended spectrum beta-lactamases. PMID- 17850341 TI - Prospective study of Clostridium difficile infections in Europe with phenotypic and genotypic characterisation of the isolates. AB - A 2-month prospective study of Clostridium difficile infections was conducted in 38 hospitals from 14 different European countries in order to obtain an overview of the phenotypic and genotypic features of clinical isolates of C. difficile during 2005. Of 411 isolates from diarrhoeagenic patients with suspected C. difficile-associated diarrhoea (CDAD), 354 were toxigenic, of which 86 (24.3%) were toxin-variant strains. Major toxinotypes included toxinotypes 0 (n = 268), V (n = 28), VIII (n = 22) and III (n = 25). MICs of metronidazole, vancomycin, erythromycin, clindamycin, moxifloxacin and tetracycline were determined using the Etest method. All the toxigenic strains were fully-susceptible to metronidazole and vancomycin. Resistance to erythromycin, clindamycin, tetracycline and moxifloxacin was found in 44.4%, 46.1%, 9.2% and 37.5% of the isolates, respectively. Sixty-six different PCR ribotypes were characterised, with the 027 epidemic strain accounting for 6.2% of isolates. This strain was positive for binary toxin genes, had an 18-bp deletion in the tcdC gene, and was resistant to both erythromycin and moxifloxacin. The mean incidence of CDAD was 2.45 cases/10 000 patient-days, but this figure varied widely among the participating hospitals. Patients infected with the 027 strain were more likely to have a severe disease (OR 3.29, 95% CI 1.19-9.16, p 0.008) and to have been specifically treated with metronidazole or vancomycin (OR 7.46, 95% CI 1.02-154, p 0.02). Ongoing epidemiological surveillance of cases of CDAD, with periodic characterisation of the strains involved, is required to detect clustering of cases in time and space and to monitor the emergence of specific highly virulent clones. PMID- 17850342 TI - Detection of human bocavirus in children with Kawasaki disease. AB - Human bocavirus (HboV) is an emerging virus that has been implicated as a cause of acute upper and lower respiratory tract infection in children. As no serological assay is available, PCR was used to screen nasopharyngeal, serum or stool samples from 16 patients with Kawasaki disease for HBoV nucleic acid. HBoV was identified by PCR in five (31.2%) patients, suggesting that this emerging virus may also play a pathogenic role in some cases of Kawasaki disease. PMID- 17850343 TI - Serological responses to Cryptosporidium in human populations living in areas reporting high and low incidences of symptomatic cryptosporidiosis. AB - One approach to investigating differences in the reported incidence of disease is to measure the extent of exposure to the organism in question by testing for a specific antibody response. IgG responses to Cryptosporidium sporozoite antigens of low molecular size in adults have been shown to be consistent and of sufficient intensity to act as reliable markers of exposure. This study used a western blot procedure to investigate the relative intensity of IgG antibody responses to the 15/17-kDa Cryptosporidium sporozoite antigen complex and the 27 kDa antigen in sera from two cities in north-west England: Liverpool (low numbers of clinical cases reported) and Preston (high numbers reported). The intensity of antibody response to the 15/17-kDa antigen complex was significantly greater in the Liverpool sera, but there was no significant difference in intensity of response to the 27-kDa antigen. The relationship between diagnosed and reported cryptosporidiosis infections and infections identified by serological testing is complex, but could indicate a protective effect resulting from either exposure to non-pathogenic strains or from repeated low-level exposure to pathogenic strains. PMID- 17850344 TI - Epidemiology of invasive Streptococcus pyogenes infections in Germany, 1996-2002: results from a voluntary laboratory surveillance system. AB - A nationwide voluntary laboratory-based surveillance study of invasive Streptococcus pyogenes (group A streptococcus; GAS) infections was conducted in Germany between 1996 and 2002. Demographical and clinical information concerning the patients was obtained from the medical files. Multiple logistic regression analysis was used to determine risk-factors for fatal outcome. Invasive isolates were obtained from 475 patients, with 251 (52.8%) of the isolates cultured from blood. The most frequent emm types were emm1 (36.4%), emm28 (8.8%) and emm3 (8%). The speA, speC and ssa genes were present at variable frequencies in different emm types. The highest frequencies of speA and speC were found in emm1 (speA, 93.6%) and emm4 (speC, 94.7%), respectively. The estimated annual incidence of invasive GAS disease for 1997-2002 was 0.1 cases/100 000 individuals. This apparently low incidence rate might be explained by the voluntary nature of the surveillance system, resulting in relatively few cases being referred to the laboratory. Complete clinical information was available for 165 cases. The overall case fatality rate was 40.6%, and was highest (65.2%) in the group aged 60-69 years. Shock, an age of >or=30 years and adult respiratory distress syndrome were predictors of a fatal outcome in a multiple logistic regression analysis. Overall, 6.7% of the cases were considered to be nosocomial, and nine cases of puerperal sepsis were observed. The study underscores the importance of invasive S. pyogenes disease in Germany. PMID- 17850345 TI - A PCR-based method to differentiate between Acinetobacter baumannii and Acinetobacter genomic species 13TU. AB - A new PCR-based method that exploits differences in gyrB gene sequences was developed to distinguish between Acinetobacter baumannii and Acinetobacter genomic sp. 13TU. Among 118 clinical and reference Acinetobacter strains, 102 of which were previously speciated by amplified rDNA restriction analysis as belonging to the Acinetobacter calcoaceticus-A. baumannii complex, the method correctly identified 31 A. baumannii and 54 Acinetobacter genomic sp. 13TU isolates to the species level. The method was rapid, specific and easy to interpret. PMID- 17850346 TI - Persistent strains of coagulase-negative staphylococci in a neonatal intensive care unit: virulence factors and invasiveness. AB - Coagulase-negative staphylococci (CoNS) are the major cause of nosocomial bacteraemia in neonates. The aim of this study was to investigate whether persistent strains of CoNS possess specific bacterial characteristics as compared with sporadic non-cluster isolates. In total, 180 blood culture isolates (95 contaminants and 85 invasive isolates) obtained from a single neonatal unit over a 12-year period were studied. Pulsed-field gel electrophoresis (PFGE) identified 87 persistent CoNS strains (endemic clones). The two largest PFGE clusters belonged to a single clonal complex according to multilocus sequence typing. Patients colonised or infected with endemic clones were of lower gestational age than those infected with non-cluster strains. One Staphylococcus haemolyticus cluster appeared to selectively colonise and infect the most extreme pre-term infants. Endemic clones were characterised by high levels of antibiotic resistance and biofilm formation. All 51 isolates belonging to the two largest PFGE clusters were ica operon-positive. Genes encoding Staphylococcus epidermidis surface protein B and the production of phenol-soluble modulins (PSMs) were also more prevalent among endemic clones than among non-cluster strains. However, endemic clones were not more prevalent among invasive isolates than among contaminants. These findings indicate that multiple selective factors, including antibiotic resistance, biofilm formation, surface proteins with adhesive properties, and PSMs regulated by agr, increase the ability of CoNS to persist in a hospital environment. It may be more prudent, when searching for new therapeutic targets, to focus on ubiquitous components of CoNS instead of putative virulence factors that do not clearly contribute to increased invasive capacity. PMID- 17850347 TI - High prevalence of carbapenem-hydrolysing oxacillinases in epidemiologically related and unrelated Acinetobacter baumannii clinical isolates in Spain. AB - Carbapenem-hydrolysing oxacillinases are reported increasingly in Acinetobacter baumannii. This study investigated the role of these beta-lactamases in causing resistance to carbapenems in 83 epidemiologically related and unrelated imipenem resistant A. baumannii clinical isolates. The isolates were also analysed for the presence of ISAba1 in the promoter region of the bla(OXA-51)-like gene in order to investigate the role of ISAba1 in OXA-51 expression. All clinical isolates contained a bla(OXA-51)-like gene, 20% contained a bla(OXA-58)-like gene, and 42% contained a bla(OXA-40)-like gene; bla(OXA-23)-like, bla(IMP) and bla(VIM) genes were not detected in any of the isolates investigated. ISAba1 was found in 24 (82.7%) of 28 pulsetypes, and was located in the promoter region of the bla(OXA 51)-like gene in five (20.8%) of these pulsetypes. Expression of bla(OXA-51) was detected in the five isolates with ISAba1 located in the promoter region, but was not detected in an isogenic imipenem-susceptible A. baumannii isolate that did not have ISAba1 located in the promoter region. It was concluded that there is a high prevalence of oxacillinases with activity against carbapenems among genetically unrelated A. baumannii clinical isolates from Spain, and that concomitant expression of two carbapenemases (OXA-51-like and either OXA-40-like or OXA-58-like) may take place. Insertion of an ISAba1-like element in the promoter of the bla(OXA-51)-like gene promotes the expression of this gene, although this did not seem to play a major role in carbapenem resistance. PMID- 17850348 TI - Occipital nerve blockade in chronic cluster headache patients and functional connectivity between trigeminal and occipital nerves. AB - Headache syndromes often involve occipital and neck symptoms, suggesting a functional connectivity between nociceptive trigeminal and cervical afferents. Although reports regarding effective occipital nerve blockades in cluster headache exist, the reason for the improvement of the clinical symptoms is not known. Using occipital nerve blockade and nociceptive blink reflexes, we were able to demonstrate functional connectivity between trigeminal and occipital nerves in healthy volunteers. The R2 components of the nociceptive blink reflex and the clinical outcome in 15 chronic cluster headache patients were examined before and after unilateral nerve blockade of the greater occipital nerve with 5 ml prilocain (1%) on the headache side. In contrast to recent placebo-controlled studies, only nine of the 15 cluster patients reported some minor improvement in their headache. Six patients did not report any clinical change. Exclusively on the injection side, the R2 response areas decreased and R2 latencies increased significantly after the nerve blockade. These neurophysiological and clinical data provide further evidence for functional connectivity between cervical and trigeminal nerves in humans. The trigeminocervical complex does not seem to be primarily facilitated in cluster headache, suggesting a more centrally located pathology of the disease. However, the significant changes of trigeminal function as a consequence of inhibition of the greater occipital nerve were not mirrored by a significant clinical effect, suggesting that the clinical improvement of occipital nerve blockades is not due to a direct inhibitory effect on trigeminal transmission. PMID- 17850349 TI - Migraine pain location at onset and during established headaches in children and adolescents: a clinic-based study from eastern India. AB - Literature documenting the location of pain at onset of migraine attacks and during established headaches in children and adolescents is sparse. Through a prospective study (2003-2005) of 200 children with migraine (ICHD-2: 1.1 and 1.2.1), we set out to document (i) the site of onset of pain and (ii) the location of pain during established attacks (on >50% of occasions) through semistructured interviews of patients and parents. Of the 200 children, the male:female ratio was 118 : 82 (1 : 0.69), the age range was 7-15 years (mean 11.8 years) and the duration of migraine 6 months to 4 years (mean 1.6 years). Ninety-three percent of subjects were ethnic Bengalis from the eastern Indian state of West Bengal, capital city Calcutta. Migraine types were: 1.1, 197 (98.5%); 1.2.1, three (1.5%). Location of pain at onset: 20.5% of subjects had unilateral onset; of these, 26.8% had eye pain, 65.9% frontal and 12.3% temporal pain. Thirty-three percent had bilateral location of pain, mostly bifrontal or ocular. None had vertex onset pain. However, in 35% of subjects, pain was holocranial at onset. Only 11.5% experienced pain in the occipito-cervical region at onset. Location of established headaches: in 53.7% of subjects with unilateral onset, headaches subsequently became holocranial. Hemicranial headaches occurred in only 19.5%. Of bilateral onset pains, 57.8% also became holocranial subsequently. In all, 73.5% of children ultimately experienced holocranial headaches. This study documents pain location at onset and during established headaches in children with migraine largely from a specific ethnic group. PMID- 17850350 TI - Tension-type headache and physical activity: an actigraphic study. AB - There have been some studies on the relationship between tension-type headache (TTH) and physical activity. However, most previous studies were not prospective and assessed physical activity by questionnaire. Therefore, this study was aimed to investigate the relationship between TTH intensity and physical activity prospectively utilizing computerized ecological momentary assessment and actigraphy. Thirty-one TTH patients wore watch-type computers equipped with actigraphy inside for 1 week to record momentary headache intensity and physical activity. Multilevel modelling was used to investigate the effect of headache intensity on the simultaneous and subsequent activity level. There were significant negative associations between headache intensity and the simultaneous and subsequent activity level, and activity level was significantly reduced at headache exacerbations. These results provide objective and quantitative evidence suggesting that TTH negatively affects physical activity. PMID- 17850351 TI - Nerve growth factor and ATP excite different neck muscle nociceptors in anaesthetized mice. AB - Neck muscle nociception probably plays a major role in the pathophysiology of tension-type headache. Recent studies have demonstrated sustained facilitation of brainstem nociception due to noxious neck muscle input evoked by nerve growth factor (NGF) or alpha,beta-methylene ATP (ATP) in mice. Hypothesized different afferent pathways in NGF and ATP models were addressed by local application of tetrodotoxin (TTX) in neck muscles. Brainstem nociception was monitored in 55 anaesthetized mice by the jaw-opening reflex elicited by electrical tongue stimulation. Sole administration of 100 nmol/l ATP or 0.8 micromol/l NGF evoked sustained reflex facilitation for at least 95 min. Preceding TTX administration prevented ATP-induced facilitation, but was without effect on NGF. Subsequent administration of 100 nmol/l TTX reversed ATP-evoked facilitation, but was ineffective on NGF. Divergent effects of TTX suggest preferential excitation of group III muscle afferents by ATP and group IV by NGF. Thus, both models address different pathways in pericranial pain. PMID- 17850352 TI - Cluster headache triggered by high-dose gestagens in the context of in vitro fertilization: a case report. PMID- 17850353 TI - Anne Frank's headache. AB - There are a significant number of famous people who suffered from frequent headaches during their lifetime while also exerting an influence of some kind on politics or the course of history. One such person was Anneliese Marie Frank, the German-born Jewish teenager better known as Anne Frank, who was forced into hiding during World War II. When she turned 13, she received a diary as a present, named it 'Kitty' and started to record her experiences and feelings. She kept the diary during her period in hiding, describing her daily life, including the feeling of isolation, her fear of being discovered, her admiration for her father and her opinion about women's role in society, as well as the discovery of her own sexuality. She sometimes reported a headache that disturbed her tremendously. The 'bad' to 'terrifying' and 'pounding' headache attacks, which were accompanied by vomiting and during which she felt like screaming to be left alone, matched the International Headache Society criteria for probable migraine, whereas the 'more frequent headaches' described by Anne's father are more likely to have been tension-type headaches than headaches secondary to ocular or other disorders. PMID- 17850354 TI - Migraine with isolated facial pain: a diagnostic challenge. AB - We present a series of seven migraine patients with typical features of a migraine attack without aura, but atypical pain localization in the face in one or both of the lower two distributions of the trigeminal nerve (V2 and V3). All of them responded well to triptans. Three patients responded to preventive treatment for migraine with beta-blockers (n = 2) or valproic acid (n = 1). These cases underline the heterogenic clinical presentation of migraine, which is sometimes difficult to diagnose even for headache specialists, and broaden the pathophysiological understanding of trigeminal nociceptive processing in migraine in the light of neuronal plasticity. PMID- 17850355 TI - Cytogenetically invisible microdeletions involving PITX2 in Rieger syndrome. AB - Axenfeld-Rieger syndrome (ARS) is a genetically heterogeneous autosomal dominant disorder mainly characterized by developmental defects of the anterior segment and extraocular anomalies. ARS shows great clinical variability and encompasses several conditions with overlapping phenotypes, including Rieger syndrome (RS). RS is characterized by developmental defects of the eyes, teeth and umbilicus, and the main causative gene is PITX2 (paired-like homeodomain transcription factor 2, or RIEG1) at 4q25. PITX2 mutations show great variety, from point mutations to microscopic or submicroscopic deletions, and apparently balanced translocations in few cases. We identified cytogenetically undetectable submicroscopic deletions at 4q25 in two unrelated patients diagnosed with RS. One patient had a t(4;17)(q25;q22)dn translocation with a deletion at the 4q breakpoint, and the other patient had an interstitial deletion of 4q25. Both deletions included only the PITX2 and ENPEP (glutamyl aminopeptidase) genes. PMID- 17850357 TI - Prenatal diagnosis of Miller-Dieker syndrome by ultrasound and molecular cytogenetic analysis. PMID- 17850358 TI - The antibody response to Propionibacterium acnes is an independent predictor of serum prostate-specific antigen levels in biopsy-negative men. AB - OBJECTIVE: To investigate whether the serum titres of Propionibacterium acnes antibodies in patients undergoing prostate biopsy are associated with prostate cancer or markers of prostate disease, including serum prostate-specific antigen (PSA) levels. PATIENTS AND METHODS: The cell wall-associated proteins from P. acnes types IA, IB and II were extracted and characterized by Western blotting and immunoblotting. We developed an enzyme-linked immunosorbent assay (ELISA) based on extracted proteins to determine the anti-P. acnes antibody titres in the sera of 68 patients undergoing prostate biopsy. Correlations between these titres and multiple markers of prostate disease were investigated. RESULTS: In patients with biopsies negative for cancer, a high anti-P. acnes antibody titre was associated with high serum PSA levels (>or=10.0 ng/mL, P = 0.04), and multiple linear regression analysis identified antibody titre as the predominant independent predictor of serum PSA level (P = 0.03). The titre was positively correlated with patient age, prostate volume and aggressive inflammation, suggesting an involvement with benign prostatic hyperplasia (BPH). However in patients with histologically detected cancer, the volume of cancer in the biopsy cores was the predominant independent predictor of serum PSA (P = 0.01). CONCLUSIONS: These results support our hypothesis that P. acnes might be involved in the development of inflammation-related prostate diseases, in particular with BPH. Our ELISA might be valuable for identifying P. acnes infection of the prostate gland in patients with elevated serum PSA levels but a negative biopsy, and might identify men at risk of developing clinical BPH. However, an investigation with more patients is needed to confirm these preliminary findings. PMID- 17850359 TI - Macroscopic, but not microscopic, perivesical fat invasion at radical cystectomy is an adverse predictor of recurrence and survival. AB - OBJECTIVE: To examine whether the presence of microscopic (pT3a) or macroscopic (pT3b) disease worsens the prognosis relative to pT2 disease at radical cystectomy, as the prognostic significance of pT3a vs pT3b perivesical fat invasion (pT3) is controversial. PATIENTS AND METHODS: In all, 242 patients with pT3 disease (pT3a in 88, pT3b in 121) had radical cystectomy and bilateral pelvic lymphadenectomy for transitional cell carcinoma of the urinary bladder; they were compared with 172 who had organ-confined muscle-invasive disease (pT2). For the analyses we used univariable and multivariable Cox regression models of recurrence and cancer-specific survival, adjusted for age, tumour grade, lymphovascular invasion and the presence of lymph node metastases. RESULTS: In multivariable analyses, microscopic perivesical fat extension (pT3a) was not associated with higher recurrence (P = 0.3) or the mortality rate (P = 0.06) vs pT2 disease. Conversely, the presence of deep perivesical fat extension (pT3b) was associated with 1.8 times the rate of recurrence (P = 0.002) and with twice the rate of death (P = 0.001) vs pT2 disease. CONCLUSION: These findings imply that a detailed assessment of the cystectomy specimen for the presence of microscopic perivesical fat invasion might not be necessary, as the presence of pT3a disease has no strong effect on recurrence or mortality. Moreover, patients with pT3a disease might not require more aggressive therapy than their counterparts with pT2 disease. However, further validation of our data is required. PMID- 17850360 TI - Bladder carcinoma among live-donor renal transplant recipients: a single-centre experience and a review of the literature. AB - OBJECTIVES: To present our experience with bladder cancer among a renal transplant population and to review critically the relevant literature. PATIENTS AND METHODS: In all, 1865 renal graft recipients were followed for a mean (SD) of 6.5 (5) years. Seven recipients (all men) developed a urothelial bladder tumour. The stage and grade of the tumours were determined. The method of the treatment was selected on the basis of the tumour characteristics and graft function. Patients were regularly followed; the endpoints were cancer-specific survival, recurrence or metastasis. RESULTS: All patients presented with gross haematuria. There was non-muscle-invasive disease in two patients who were treated by transurethral resection and adjuvant intravesical bacille Calmette-Guerin immunotherapy. One patient died 24 months later due to complications of end-stage renal disease. To date the second patient is alive and free of the recurrence. Five recipients with muscle-invasive disease had a radical cystectomy and orthotopic bladder substitution. The mean (sd) time to the last follow-up or death was 14.6 (3.1) months. Three patients died with stable graft function; two from distant metastasis and one from a cerebrovascular stroke. The remaining two patients are still alive, free of disease and with good graft function. CONCLUSIONS: Urothelial bladder tumours are generally uncommon. The presence of haematuria in renal allograft recipients should be thoroughly investigated. Early diagnosis and prompt treatment are required for managing such tumours, because they are aggressive. Orthotopic bladder substitution is feasible with a good functional outcome for patients in whom cystectomy is indicated. PMID- 17850361 TI - Active surveillance; a reasonable management alternative for patients with prostate cancer: the Miami experience. AB - OBJECTIVE: To examine the outcome of patients diagnosed with 'low-risk' prostate cancer managed by active surveillance (AS). PATIENTS AND METHODS: In all, 157 men with localized prostate cancer were followed on AS. The inclusion criteria for AS included: Gleason score of < or = 6, a serum prostate-specific antigen (PSA) level of < or = 15 ng/mL, stage < or = T2, low-volume disease and > 12 months of follow-up. The follow-up was rigorous, with PSA tests and a digital rectal examination every 3 months for 2 years, and a repeat biopsy 6-12 months after the initial diagnosis and yearly when indicated. Continuance of AS was based on the PSA doubling time, re-biopsy score, Gleason score, tumour volume, stage progression and patient preference. RESULTS: In all 99 patients met the inclusion criteria; their mean age at diagnosis was 66 years, their mean PSA level 5.77 ng/mL and the mean follow-up 45.3 months. On initial repeat biopsy, 63% had no cancer and 34% had a Gleason sum of < or = 6. Eight patients were treated (three with hormones; five with curative intent); two had radical prostatectomy (one had pT2c pNO Gleason 7 disease); three had radiotherapy. The probability is that 85% would remain treatment-free at 5 years; no patient died from prostate cancer. The PSA doubling time and clinical stage at diagnosis were predictive of progression. CONCLUSION: Patients who are followed on AS must be selected using narrowly defined inclusion criteria and closely followed with a standard regimen of PSA testing, digital rectal examination and repeat biopsy. PMID- 17850362 TI - The maximum tumour length in biopsy cores as a predictor of outcome after radical prostatectomy. AB - OBJECTIVES: To evaluate maximum tumour length (MTL) in biopsy cores as a predictor of prostate-specific antigen (PSA)-failure, systemic failure, and death from prostate cancer after radical prostatectomy (RP). PATIENTS AND METHODS: We assessed 209 men with clinically localized prostate cancer treated with RP; preoperative variables were correlated with unfavourable pathological characteristics in the RP specimens and with outcome after surgery, using univariate and multivariate analysis. RESULTS: The median (range) MTL was 4 (0.2 19) mm and correlated with adverse pathological findings, including specimen Gleason score (P = 0.003), pT3 (P < 0.001), seminal vesicle invasion (P < 0.001) and lymph node involvement (P = 0.019) in multivariate analysis. Preoperative PSA (P < 0.001), biopsy Gleason score (P = 0.002), and MTL (P = 0.045) were independent predictors of PSA failure, whereas only MTL remained a predictor of systemic-failure (P < 0.001) and death from prostate cancer (P = 0.004). The median (range) follow-up after surgery was 90 (17-152) months, during which 83 patients had PSA failure, 20 developed systemic failure and 15 died from prostate cancer. CONCLUSIONS: The MTL correlates well with adverse pathological findings and appears to be an independent predictor of outcome after RP. Patients with a greater MTL might have cancer with an aggressive phenotype and therefore be candidates for more aggressive therapies. PMID- 17850363 TI - Frozen section-guided wide local excision in the treatment of penoscrotal extramammary Paget's disease. AB - OBJECTIVE: To analyse the clinicopathological characteristics of penoscrotal extramammary Paget's disease (EMPD) and to discuss the outcomes after frozen section-guided wide local excision. PATIENTS AND METHODS: From 1990 to 2005, at our institution, 38 patients with penoscrotal EMPD received wide local excision with intraoperative frozen-section analysis. Their medical records were reviewed for patient demographics, lesion characteristics, surgical margin status, and clinical outcome. RESULTS: No patients had EMPD secondary to a non-cutaneous malignancy; 23 patients had intraepithelial EMPD, 12 had invasive EMPD and three had EMPD with underlying adnexal adenocarcinoma. The median (range) largest diameter of the lesion was 6 (1-20) cm. Of 38 patients, 12 (32%) had positive frozen-section results and had extended surgical excision until a negative margin was obtained. Additional margin examination of the gross specimen and final examination of the frozen sections showed that five patients had false-negative results. There was a microscopic positive margin in 15 of 38 (40%) patients when a conventional 2 cm clinical tumour-free border was maintained. Skin erythematous patches were significantly correlated with the spread of disease (P = 0.03). After a median (range) follow-up of 33.5 (3-140) months, six of 38 (16%) patients had recurrent disease, of whom only two had recurrent skin lesions, while four had systemic progression. CONCLUSION: Frozen section-guided wide local excision gave an acceptable recurrence rate in the treatment of penoscrotal EMPD. Primary EMPD with dermal invasion should be actively monitored for possible aggressive behaviour. PMID- 17850364 TI - Surveillance of patients with bladder carcinoma using fluorescent in-situ hybridization on bladder washings. AB - OBJECTIVES: To compare the sensitivity and specificity of the UroVysion (Abbott Laboratories Inc., Downers Grove, IL, USA) fluorescent in-situ hybridization (FISH) assay to that of urinary cytology obtained from bladder irrigation during cystoscopic surveillance in patients with bladder carcinoma. PATIENTS AND METHODS: The medical records were retrospectively reviewed for 41 consecutive patients screened at the authors' institution between August 2000 and December 2006 for recurrence of pathologically confirmed bladder cancer. All 162 cytology examinations and 141 FISH assay results obtained from bladder washing were included. Recurrence was determined by cystoscopy, bladder biopsy and upper-tract imaging. Sensitivity, specificity, positive predictive and negative predictive values were assessed using a chi-square distribution with one degree of freedom. RESULTS: There were 24 men and 17 women (male to female ratio 0.59), the mean (range) age was 56 (33-73) years and the mean follow-up 30 (2-57) months. At the initial diagnosis, 35 of the 41 patients (85%) had superficial tumours (stage or=T2). Twenty-six (63%) had low-grade and 15 (37%) had high-grade tumours. In 16 of 141 (11%) of the FISH assays and 16 of 162 (10%) of the cytological samples that were collected from bladder irrigations, there were too few cells for an adequate analysis. The FISH assay correctly correlated with subsequent cystoscopy, bladder biopsy or upper-tract imaging in 110/125 (88%) cases but not in 15/125 (12%). Cytology correctly correlated with the subsequent evaluation in 112/146 (77%) cases but did not in 34/146 (23%). When the FISH was compared with cytology in this setting, the sensitivity was 77% (30/39) vs 74% (37/50; P > 0.1), the specificity was 93% (80/86) vs 78% (75/96; P < 0.01), the positive predictive value was 83% (30/36) vs 64% (37/58; P < 0.05), and the negative predictive value was 90% (80/89) vs 85% (75/88; P > 0.1), respectively. CONCLUSION: The UroVysion FISH assay obtained from bladder washings during cystoscopic surveillance of patients with a history of bladder cancer provides a similar specificity but greater sensitivity than that of cytology for detecting bladder cancer recurrences. Given the better specificity and similar sensitivity of UroVysion compared with urine cytology obtained from bladder washings, a reasonable approach might be to use the UroVysion assay as the primary marker for recurrence, with urine cytology used as a complementary examination. PMID- 17850365 TI - Anandamide improves the impaired nitric oxide-mediated neurogenic relaxation of the corpus cavernosum in diabetic rats: involvement of cannabinoid CB1 and vanilloid VR1 receptors. AB - OBJECTIVE: To investigate the ability of acute administration of the endogenous cannabinoid, anandamide, in vitro to alter the nonadrenegic noncholinergic (NANC) mediated relaxation of corpus cavernosum (CC) in diabetic rats and the possible role of nitric oxide (NO), as it is well known that erectile dysfunction (ED) affects 35-75% of men with diabetes mellitus and several studies have been conducted to find appropriate strategies for treating diabetes-induced ED. MATERIALS AND METHODS: Diabetes was induced in rats by streptozotocin administration and was maintained for 8 weeks. The CC were removed and isolated in organ baths for pharmacological studies. Agonist-evoked or electrical-field stimulation (EFS)-evoked smooth muscle tensions in CC strips from control and diabetic rats were measured. RESULTS: The neurogenic relaxation of phenylephrine (7.5 microm)-precontracted isolated CC strips was impaired in diabetic rats. Anandamide (0.3, 1 and 3 microm) enhanced the relaxant responses to EFS in diabetic CC strips in a dose-dependent manner. This effect was antagonized by the selective cannabinoid CB(1) receptor antagonist AM251 (1 microm) and the selective vanilloid receptor antagonist capsazepine (3 microm). Concurrent administration of partially effective doses of l-arginine (10 microm) and anandamide (0.3 microm) exerted a synergistic improvement in EFS-induced relaxation of diabetic CC strips (P < 0.001). The relaxant responses to the NO donor, sodium nitroprusside, were similar between diabetic and control groups. CONCLUSION; For the first time, we show that acute administration of anandamide, an endogenous cannabinoid, alone or combined with l-arginine can improve nitrergic nerve-mediated relaxation of the CC in diabetic rats. This effect was mediated by cannabinoid CB(1) and vanilloid VR(1) receptors within the CC. PMID- 17850366 TI - Additional treatment for pT3 prostate cancer: now, later or never. PMID- 17850367 TI - Intermediate-term prospective results of radiofrequency-assisted laparoscopic partial nephrectomy: a non-ischaemic coagulative technique. AB - OBJECTIVE To report the first intermediate-term oncological outcomes of laparoscopic radiofrequency coagulation followed by laparoscopic partial nephrectomy (RF-LPN) to treat small renal masses, as LPN is limited by the technical difficulty of efficient tumour resection and parenchymal repair during warm ischaemia of the kidney. PATIENTS AND METHODS A prospective database was searched to identify patients treated with RF-LPN; in each case the tumour was first RF coagulated with a margin of normal parenchyma, and then excised. Only fibrin glue was applied to the haemostatic resection site to prevent urinary leaks. In all, 32 tumours were treated with this approach, and a radiographic follow-up was completed yearly. RESULTS All PNs were accomplished with no hilar clamping, with a mean blood loss of 80 mL; 72% of masses were renal cell carcinoma. There was a positive margin in four masses (13%); 29 tumours (mean size 1.9 cm) were eligible for analysis of oncological outcomes, with a mean follow-up of 31 months. There were no tumour recurrences at the last follow-up, giving a cancer-specific survival rate of 100%. CONCLUSIONS RF-LPN with no hilar clamping simplifies the surgical technique and appears to have excellent cancer control in the intermediate term. In the few patients with a positive surgical margin, it is possible that coagulation beyond the tumour margin kills any residual microscopic tumour, minimizing or obviating the risk of tumour recurrence. Nevertheless, vigilance during tumour excision and margin identification is mandatory. PMID- 17850368 TI - Prostate-specific antigen velocity in untreated, localized prostate cancer. AB - OBJECTIVE: To report the results of a prospective study of active surveillance of untreated prostate cancer, with a focus on baseline predictors of prostate specific antigen (PSA) velocity, as PSA velocity before treatment is an important predictor of prostate cancer mortality, and patients on active surveillance are monitored for several years to estimate the PSA velocity and thus select patients for radical treatment. PATIENTS AND METHODS: A prospective study of active surveillance for localized prostate cancer opened at the Royal Marsden Hospital in 2002. Eligible patients had clinical stage T1/T2a, N0/Nx, M0/Mx adenocarcinoma of the prostate with a serum PSA level of < 15 ng/mL, a Gleason score of < or = 7 with primary grade < or = 3, and less than half the biopsy cores positive. The PSA velocity before treatment was analysed in relation to baseline clinical characteristics. RESULTS: In all, 237 patients on surveillance were followed for a median of 24 months (median age 67 years; median initial PSA level 6.5 ng/mL; median pretreatment PSA velocity 0.44 ng/mL per year). On multivariate analysis, PSA density (i.e. serum PSA level/prostate volume) was the only significant determinant of PSA velocity (P < 0.001). Patients with a PSA density above or below the median (0.185 ng/mL/mL) had a median (interquartile range) PSA velocity of 0.92 (0.34-1.77) ng/mL per year and 0.35 (-0.06, 0.80) ng/mL per year, respectively. CONCLUSIONS: PSA density, which is readily available at the time of diagnosis, is an independent determinant of PSA velocity in untreated, localized prostate cancer. If this is confirmed, PSA density could be used to inform the often difficult choice between active surveillance and immediate radical treatment. PMID- 17850369 TI - The influence of prostate volume on prostate cancer detection using a combined approach of contrast-enhanced ultrasonography-targeted and systematic grey-scale biopsy. AB - OBJECTIVE: To evaluate the influence of prostate volume (PV) on the detection of prostate cancer using a combined approach of contrast-enhanced ultrasonography (CEUS) and grey-scale US-guided systematic biopsy (SB). PATIENTS AND METHODS: We evaluated 345 patients with prostate cancer and a total prostate-specific antigen (PSA) level of >/= 1.32 ng/mL (1.32-35.3, mean 6.6). Biopsies were taken by two independent examiners; one took five CEUS (Doppler) targeted biopsies of hypervascular regions in the peripheral zone, and subsequently the other took 10 systematic prostate biopsies. We assessed the cancer detection rates for the five different subgroups of prostate volumes, i.e. <20, 20-30, 30-40, 40-50 and > 50 mL. RESULTS: Each technique, SB and CEUS, detected 73.4% and 77.1% of all detected cancers, respectively, but there were statistically significant differences in detection rate only in small glands. Only 69.0% and 70.4% of all cancers were detected by SB in glands of <20 and 20-30 mL, respectively, whereas 88.1% and 80.8% were detected by CEUS. CONCLUSION: The prostate cancer detection rate for CEUS was significantly higher in prostates of <30 mL (48.1% of the study population) than for SB. Therefore the combined approach of CEUS and SB allows improved cancer detection in patients with small glands and low total PSA values. PMID- 17850370 TI - Lack of prognostic significance of prostate biopsies in metastatic androgen independent prostate cancer. AB - OBJECTIVE: To assess the significance of viable tumour in the prostate of patients with metastatic androgen-independent prostate cancer (AIPC). PATIENTS AND METHODS: We evaluated the clinicopathological features, including follow-up, of 40 men with metastatic AIPC who had a transrectal biopsy of the prostate. RESULTS: Prostate biopsies (median three cores per biopsy) showed viable tumour in 19 of 40 patients (48%). Of the 18 patients who had received radiotherapy (RT), nine had negative on-study biopsy results. A previous history of RT was not associated with overall survival in patients with biopsy-positive tumours (P = 0.84). Also, there was no statistically significant association between positive or negative biopsy status and overall survival (OS) in these 40 patients (P = 0.39), with a similar median OS of 19.6 months for biopsy-negative and 19.8 months for biopsy-positive patients, respectively. CONCLUSIONS: Taking prostate biopsies at the time of documented metastatic AIPC yielded tumour in about half the patients. A previous history of RT was not associated with a negative prostate biopsy; the latter appears to have no influence on the prognosis. PMID- 17850371 TI - The outcome with ureteric stents for managing non-urological malignant ureteric obstruction. AB - OBJECTIVE: To investigate the clinical outcome using ureteric stents to manage ureteric obstruction in advanced non-urological malignancies. PATIENTS AND METHODS: We retrospectively reviewed the use of ureteric stents (Endo-sof, Cook Urological, Spencer, IN, USA) placed for malignant ureteric obstruction from June 2001 to September 2006. The clinical and radiological variables for predicting the failure of stent insertion, functional stent failure and death were analysed. RESULTS: In all, 86 patients with a non-urological malignant ureteric obstruction were treated by ureteric stenting; 13 (15%) had failure of retrograde stent insertion, and of the remaining 73, 12 (16%) had stent failures during the subsequent follow-up. The risk of failure for stent insertion significantly increased with male gender (hazard ratio 6.45, P = 0.028) and the presence of bladder invasion (hazard ratio 27.04, P < 0.001). There was no independent predictor of stent failure in univariate analysis. Of the 86 patients, 54 (63%) died with a mean survival time of 8.6 months after an initial attempt to place a stent, and 41 (48%) died within 1 year. Multivariate analysis showed that low performance status, upper ureteric obstruction and no chemotherapy after stenting were independently associated with a poor prognosis (P = 0.03, 0.004 and 0.003, respectively). CONCLUSION: The method of diversion for a malignant ureteric obstruction should be carefully discussed with male patients or if there is bladder invasion. Patients with a low performance status, upper ureteric obstruction and no scheduled chemotherapy after stenting had a poor survival time. PMID- 17850372 TI - A 10-year retrospective audit of penile cancer management in the UK. AB - OBJECTIVE: To audit the penile cancer workload, management and outcome within a regional cancer network serving a population of approximately 1 million in the West Midlands (UK), comparing these data to that published by the British Association of Urological Surgeons National Cancer Registry, the UK National Institute of Clinical Excellence and the European Associations of Urology guidelines. PATIENTS AND METHODS: Patients diagnosed with or treated for penile cancer within the Arden Cancer Network over a 10-year period were identified retrospectively, and data relating to histology, local treatment, lymph node management, outcome and survival were recorded. RESULTS: Data were obtained for 65 patients; 61 (94%) had histologically confirmed squamous cell carcinoma (SCC) of the penis, equating to approximately 0.6 cases per 100 000 population per year. Their mean age at diagnosis was 63 years. Of SCCs, 86% were located on the glans and/or foreskin. Thirty-six patients had conservative primary local therapy, mostly for T0 or T1 disease. The 5-year relapse-free survival after radiotherapy was 63%, although survival after salvage penectomy was 75% at 4 years. Forty-seven patients had lymph node surveillance; 11 developed lymph node disease and had lymph node dissection (LND) with or with no radiotherapy, but survival was poor. Primary inguinal LND with or without radiotherapy was used in eight patients, and was associated with a good survival, although three were found to have negative histology after LND. Survival was strongly influenced by T and N stage at presentation and the 5-year survival for the whole group was 71%. CONCLUSION: The workload, incidence and overall mortality from penile cancer within the Arden Cancer Network are in line with those in the rest of the UK. Rates of conservative therapy were good in this group and associated with good survival. Survival could be improved by identifying and aggressively treating those patients at high risk of lymph node disease. PMID- 17850373 TI - Effect of letrozole on urinary bladder function in the female rabbit. AB - OBJECTIVE: To investigate the effect of letrozole (a potent aromatase inhibitor that effectively inhibit the synthesis of oestrogen) on bladder contraction with changes in morphology and biochemistry. MATERIALS AND METHODS: Sixteen female New Zealand white rabbits were separated into four equal groups; groups 1-3 were given oral letrozole for 1, 2 and 3 weeks, and group 4 was given saline and served as the control group. At the end of the medication period each rabbit was anaesthetized and the bladder muscle strips were used for contractile, histological and biochemical studies. RESULTS: The concentration of serum oestrogen was significantly lower and testosterone was significantly higher in letrozole-treated rabbits than in the control group. The rabbits treated for 1 week with letrozole showed significant decreases in the contractile responses to electrical field stimulation, ATP and carbachol, but not to KCl. Contractility returned to normal in the rabbits treated for 2 and 3 weeks. Letrozole resulted in an increased volume percentage of collagens and decreased bladder compliance. The volume percentage of the smooth muscle component also changed, with a significant decrease at 1 week and then a gradual increase at 2 and 3 weeks. Contractile dysfunction was absent at 2 and 3 weeks, which was consistent with no change in sarcoplasmic reticulum Ca(2+)-ATPase content or mitochondrial function. CONCLUSIONS: The bladder contractility decline in the first week and was restored at 2 and 3 weeks. The present study unexpectedly showed the possibility that testosterone might be as important as oestrogen in the contractile function of the female bladder. PMID- 17850374 TI - Effect of autologous blood transfusion on the rate of biochemical recurrence after radical prostatectomy. AB - OBJECTIVE: To test the association between autologous blood transfusion (ABT) and biochemical recurrence (BCR) after radical prostatectomy (RP) in a large group of contemporary patients. PATIENTS AND METHODS: We analysed 1291 patients treated with RP; Kaplan-Meier analysis was used to graphically explore the association between ABT and BCR. Cox regression models addressed the association between ABT and BCR in univariate and multivariate analyses, after adjusting for preoperative prostate specific antigen level, pathological Gleason sum, extracapsular extension, seminal vesicle invasion and lymph node invasion. RESULTS: Of all patients, 205 (15.4%) received perioperative ABT. The mean (median, range) follow up was 43.2 (40.9, 0.3-145) months. BCR was recorded in 347 (26.9%) patients and the time to BCR was 25.2 (20.5, 0.3-107) months. Neither in univariate (P = 0.053) nor in multivariate (P = 0.2) Cox regression analyses was ABT a statistically significant or independent predictor of BCR. CONCLUSION: Perioperative ABT does not predispose to a higher rate of BCR in patients after RP. PMID- 17850375 TI - Molecular markers and mortality in prostate cancer. AB - OBJECTIVE: To evaluate prognosis in prostate cancer by assessing the independent effect of selected molecular factors (e.g. markers of cell-cycle regulation), in addition to the effect of traditional clinical factors (e.g. anatomical stage, histological grade), in predicting long-term mortality among men newly diagnosed with prostate cancer. PATIENTS AND METHODS: In a community-based population of 64 545 USA veterans aged >/= 50 years and receiving ambulatory care during 1989-90 at nine Veterans Affairs (VA) medical centres in New England, 1274 had incident prostate cancer during 1991-95. We obtained the medical records and diagnostic tissue for these men, and then extracted demographic data and clinical information, and conducted immunohistochemical assays of molecular markers in biopsy tissue, as potential prognostic factors. In this interim analysis, data on 250 patients were analysed; the main outcome was overall mortality to 31 December 2003, providing 8-13 years of follow-up. RESULTS: In 228 (91%) patients with available medical record and laboratory data, the median age was 72 years and the median prostate-specific antigen level was 10.4 ng/mL. In adjusted (multivariate) analyses that included traditional prognostic factors, bcl-2 staining (hazard ratio 2.14, 95% confidence interval 1.27-3.58, P = 0.004) and high microvessel density (1.76, 1.19-2.60; P = 0.005) had an independent effect on the outcome. CONCLUSIONS: Bcl-2 and microvessel density are independent predictors of subsequent death among men with prostate cancer and might have a clinical role in assisting in deciding on treatment. PMID- 17850376 TI - Right laparoscopic donor nephrectomy and the use of inverted kidney transplantation: an alternative technique. AB - OBJECTIVES: To report a novel approach to overcome the problems associated with a short right renal vein harvested by clipping the vein during right laparoscopic donor nephrectomy (RLDN). PATIENTS AND METHODS: This prospective study included 32 donors and their recipients; all donors had transperitoneal RLDN. The right renal artery and vein were ligated by Hem-o-lok and titanium clips, which resulted in a very short renal vein (<1.5 cm). When the kidney was positioned inverted in the recipient, the renal vein was placed posteriorly, adjacent to the external iliac vein, making a safe and simple venous anastomosis possible. RESULTS: All RLDN were completed with no conversion or re-operation. The mean (range) warm ischaemia time was 9.59 (3-17) min and there was no malfunction of the vascular clips on the major vessels. After a mean follow-up of 14 months the recipient survival rate was 97%. Graft function was excellent, with a mean (sd) serum creatinine level of 1.35 (0.31) mg/dL at 3 months after surgery, and there was no renal artery or vein thrombosis in any of the grafts. There were two ureteric complications (6%), i.e. one ureterocutaneous fistula resolved by secondary ureteroureterostomy, and one stricture at the site of ureteric anastomosis, which was managed by ureteroneocystostomy. CONCLUSION: The right renal vein obtained by LDN, after clipping the renal vein, is quite short, but by placing the kidney upside-down in the right iliac fossa transplantation is possible with no increased incidence of vascular thrombosis. This simple modification might obviate the need for removing a patch from the inferior vena cava, which is a challenging procedure for laparoscopic surgeons during RLDN. PMID- 17850377 TI - The retroperitoneal laparoscopic Hellstrom technique for pelvi-ureteric junction obstruction from a crossing vessel. AB - OBJECTIVE: To report our experience with the treatment of pelvi-ureteric junction obstruction (PUJO) using the retroperitoneal laparoscopic Hellstrom (RLH) technique to relocate the crossing vessel. PATIENTS AND METHODS: We used the RLH technique selectively in eight patients with PUJO from an aberrant crossing vessel, according to observations during surgery. The crossing vessel was mobilized and embedded in the generous pelvic wall with 4-0 polyglactin sutures to relieve the PUJO. Follow-up studies included intravenous urography, ultrasonography and renal functional scintigraphy at 1 month after surgery and every 3 months thereafter. RESULTS: The mean (range) operative duration was 45 (40-60) min; the blood loss was negligible. Crossing vessels were identified to be anterior to the renal pelvis in two patients and posterior in six. The hospital stay after surgery was 5 (4-7) days. No paregoric was required after surgery. The collecting systems were intact and no JJ stent was required in any patient. The mean (range) follow-up was 13.6 (12-15) months. In all patients the obstruction was resolved or significantly improved, and there were no complications, e.g. urine leakage and infection. A long-term follow-up is mandatory. CONCLUSIONS: The RLH technique is a minimally invasive alternative for patients with PUJO caused by a crossing vessel. Embedding the crossing vessels in the pelvic wall is feasible and safe for such patients; empirical judgement during surgery is prudent for success. PMID- 17850378 TI - The incidence of chronic scrotal pain after vasectomy: a prospective audit. AB - OBJECTIVE: To assess the extent of scrotal pain in men before and after vasectomy, to produce accurate data for the benefit of men considering this procedure, and hence improved informed consent about the outcomes, as chronic scrotal pain after vasectomy is a poorly quantified clinical problem. PATIENTS AND METHODS: Between November 2004 and January 2006 nine surgeons carried out vasectomies in 625 men (mean age 39.9 years, sd 5.6) under local anaesthesia. A questionnaire was devised to establish the presence of any scrotal or testicular pain, and to characterize this discomfort; 6 months after the procedure a modified version of the same questionnaire was administered. RESULTS: In all, 593 (94.7%) men returned the preoperative questionnaires and were entered into the study; 488 (82.2%) of these completed the follow-up questionnaire, giving a mean (sd) follow-up of 6.8 (1.6) months. In all, 65 men reported new-onset scrotal pain at 7 months (14.7%). The mean visual analogue score for this pain was 3.4/10. Four men (0.9%) in the responding group described pain after vasectomy as 'quite severe and noticeably affecting their quality of life'. CONCLUSION: At 7 months after vasectomy about 15% of previously asymptomatic men have some degree of scrotal discomfort. These early data indicate that chronic scrotal pain after vasectomy is a genuine entity, but a longer-term follow-up in this group will be important to allow further evaluation of how this pain develops with time. PMID- 17850379 TI - Does a highly sensitive thyroglobulin (Tg) assay change the clinical management of low-risk patients with thyroid cancer with Tg on T4 < 1 ng/ml determined by traditional assays? AB - OBJECTIVE: To evaluate a highly sensitive thyroglobulin (Tg) assay [functional sensitivity (FS): 0.1 ng/ml] (Tg-ICMA) in low-risk patients with known Tg on T4 < or = 1 ng/ml measured by a traditional assay (FS: 1 ng/ml) (Tg-IRMA). METHODS: Tg ICMA was measured in serum samples stored at -70 degrees C. Samples were obtained 6 months or more after total thyroidectomy and remnant ablation with (131)I, during L-T4 therapy (TSH < 0.4 mIU/l). All patients had well-differentiated and completely resected tumours, no ectopic uptake on post-therapy whole-body scans and were considered to be at low risk for recurrence. On the occasion of collection and retesting for this study, Tg-IRMA was < or = 1 ng/ml in all samples and no antibody interference was observed. RESULTS: Tg-ICMA < or = 0.1 ng/ml was observed in 130/178 (73%) patients and recurrence was diagnosed in only 1/130 (0.8%). Tg-IRMA measured after L-T4 withdrawal was > 1 ng/ml in 5/130 (3.8%) patients. Forty-eight (27%) patients had Tg-ICMA > 0.1 ng/ml (0.12-1.6 ng/ml) and recurrence was diagnosed in 5/48 (10.5%). Tg-IRMA measured after L-T4 withdrawal was > 1 ng/ml in 20/48 (41.6%) patients. A negative predictive value of 100% was achieved with Tg-ICMA on T4 < or = 0.1 ng/ml combined with neck ultrasonography (US) or with stimulated Tg-IRMA < or = 1 ng/ml. CONCLUSIONS: Patients at low risk for recurrence with undetectable Tg on T4 measured by a highly sensitive assay (FS: 0.1 ng/ml) in the absence of antibody interference and with a negative sensitive neck US do not need to be submitted to Tg stimulation. Recurrence is rare in these cases and only a minority of patients convert to stimulated Tg > 1-2 ng/ml. PMID- 17850380 TI - Correspondence re commercially available allergoid products for birch pollen immunotherapy. PMID- 17850381 TI - The impact of aluminium in acid-suppressing drugs on the immune response of BALB/c mice. AB - BACKGROUND: Recently we have shown that anti-acid drugs lead to an enhanced risk of food allergy. This may be due to hindered peptic digestion, caused by an elevation of the gastric pH. Additionally, it is known that aluminium-linked antigens lead to an increased probability of sensitization. OBJECTIVE: Our aim in this study was to show whether sucralfate promotes sensitization not only by preventing peptic digestion but also by acting as a T-helper type 2 (Th2) adjuvant. METHODS: To avoid the effect of sucralfate on the gastric pH and to show only the adjuvant effect, BALB/c mice were immunized on the parenteral route with codfish extract plus sucralfate, and control groups with aluminium hydroxide (alum) (Th2 adjuvant) or monophosphoryl lipid A (MPL) (Th1 adjuvant). Antigen specific antibodies and cytokine levels were determined. The in vivo effect was investigated by intradermal skin tests. RESULTS: Codfish-specific high IgG1 and IgE antibody levels as well as elevated IL-4 and IL-5 levels in alum- and MPL treated mice, but more importantly also in sucralfate-treated mice, indicated a Th2 shift. Positive skin tests confirmed this Th2 response. CONCLUSIONS: Our data show that parenterally applied sucralfate is able to induce a Th2 response probably due to the aluminium content. This indicates that orally applied sucralfate may lead to an enhanced risk of food allergy not only by inhibiting peptic digestion but also by acting as a Th2 adjuvant. PMID- 17850382 TI - A double-blind, placebo-controlled trial of montelukast in adult atopic eczema. AB - BACKGROUND: Montelukast is an antagonist of cys-leukotriene receptors used mainly in the treatment of asthma- and seasonal-allergic rhinitis. Initial reports concerning the use of montelukast in atopic dermatitis (AD) have been encouraging, although not consistent. OBJECTIVES: We have undertaken a randomized, double-blind, parallel-group, placebo-controlled trial to investigate further the efficacy of montelukast in the treatment of atopic eczema. METHODS: Following a screening visit, subjects received placebo treatment for 2 weeks in a single-blind phase, followed after visit 2 by an 8-week, double-blind period of treatment with montelukast 10 mg daily or placebo. Subjects were patients aged 16 60 years under our care for treatment of AD of moderate severity, defined by a six-area, six-sign atopic dermatitis (SASSAD) score in the range 12-50. Response to treatment was assessed by investigators and by subjects using a seven-point scale, with response defined as marked improvement or better. In addition, the SASSAD score was used to monitor the severity of clinical signs. The proportion of skin involved was estimated and visual analogue scales were used to record the severity of pruritus and sleep disturbance. Topical corticosteroid usage was recorded using a five-point scale. Adverse events were recorded. RESULTS: Sixty subjects were recruited and 54 completed the study. The treatment groups were well matched for disease severity at baseline (SASSAD scores were 25 and 29 in the montelukast and placebo groups, respectively). There were no significant differences between the treatment groups in any of the parameters used to assess treatment response. The improvement in mean SASSAD score from baseline (visit 2) to the end of treatment was marginally superior in the placebo group, 1.41 points on montelukast vs. 1.76 on placebo, a difference of 0.35 (95% confidence interval -6.1 to 6.8). Adverse events were generally of a mild nature except for a brief septicaemic illness in one subject receiving montelukast. CONCLUSIONS: The data do not support previous reports of efficacy of montelukast in treatment of AD. PMID- 17850383 TI - Latex allergy: low prevalence of immunoglobulin E to highly purified proteins Hev b 2 and Hev b 13. AB - BACKGROUND: Hevea brasiliensis (Hev b) 2 and Hev b 13 have recently been identified as major latex allergens by detecting specific IgE antibodies in >50% of sera from Hev b latex-allergic individuals. OBJECTIVE: We assessed the prevalence rates for sensitization to extensively purified latex allergens in patients from three diverse geographical areas. METHODS: Native Hev b 2, Hev b 5, Hev b 6.01 and Hev b 13 were purified by non-denaturating chromatography and were used in ELISAs to assess sera from 215 latex-allergic patients and 172 atopic non sensitized controls from Finland, Spain and the United States to detect allergen specific IgE antibodies. RESULTS: Unexpectedly, even highly purified Hev b 13 contained epitope(s) to which Hev b 6-specific human IgE antibodies bound effectively. Further purification, however, reduced the prevalence of IgE antibody reactivity to low levels: 15%, 5% and 11% for Hev b 2, and 18%, 30% and 27% for Hev b 13 among latex-allergic Finnish, Spanish and American patients, respectively. Interestingly, Finnish patients had a lower prevalence of Hev b 5 specific IgE antibody (28%) as compared with Spanish (49%) and American (71%) patients. The prevalence of Hev b 6.01-specific IgE reactivity was uniformly >50% in all three populations. CONCLUSION: Neither Hev b 2 nor Hev b 13 appear to be major latex allergens when evaluated in serological assays using highly purified allergens. The reason(s) for the observed differences in published sensitization rates in various geographic regions requires further study. The purity of the allergen preparations has a marked impact on the accuracy of latex-specific IgE antibody detection in epidemiological studies and in the serological diagnosis of latex allergy. PMID- 17850384 TI - Why potential live renal donors prefer laparoscopic nephrectomy: a survey of live donor attitudes. AB - OBJECTIVES: To address donor attitudes and reasons for selecting either laparoscopic or open donor nephrectomy (LDN, ODN), as despite the increased interest in laparoscopic procedures, organ donation continues to lag behind the demand for organs, and many new initiatives have failed to reduce the gap. PATIENTS AND METHODS: This case series comprised a 10-year review of medical records and a transplant database on donor demographics, analgesic requirements, postoperative complications and length of hospital stay. A structured telephone interview was conducted for all live donors to evaluate donor awareness, reasons for selecting LDN and the psychosocial impact of DN on donors' rehabilitation. RESULTS: Between 1995 and 2004, 38 LDN and 38 ODN were carried out; 70% were women in both groups, with a respective mean age of 44.4 and 47.1 years. Three LDNs were converted to ODN due to technical difficulties. The mean operative duration for LDN (194.8 min) was 78 min longer than for ODN (116.8 min). As expected, the mean analgesia requirement and length of hospital stay was less for LDN than ODN, by 55.4 mg of morphine equivalent and 2.3 days. Although all renal donors were aware of the option of LDN, one patient chose ODN due to safety concerns. The primary source of donor information was derived predominantly from the donor assessment process. The main reason for choosing LDN was the earlier return to work (54%), followed by less postoperative pain (33%). In general, there was minimal psychosocial impact after renal transplantation and the overall donor experience was very positive (85%). CONCLUSION: LDN has remained a safe, less-invasive but effective technique for allograft procurement, with minimal morbidity. Overall, there is less postoperative pain and fewer surgical complications, and an earlier return to normal functioning. The level of satisfaction with the whole renal donation process was very positive, with minimal psychosocial impact. PMID- 17850385 TI - The early use of transurethral alprostadil after radical prostatectomy potentially facilitates an earlier return of erectile function and successful sexual activity. AB - OBJECTIVE: To assess whether early introduction of the Medicated Urethral System for Erection (MUSE(TM), Vivus Inc., Mountain View, CA, USA) after radical prostatectomy (RP) results in a shorter recovery time for the return to functional erections and successful sexual activity. PATIENTS AND METHODS: In a prospective study of 91 sexually active men who had a nerve-sparing RP for prostate cancer, 56 were treated with MUSE (125 or 250 microg three times per week for 6 months) while the remaining 35 had no erectogenic aids, except as necessary when attempting sexual activity. Self-administration of MUSE was initiated approximately 3 weeks after RP. Treatment efficacy was analysed by the patient's response to the Sexual Health Inventory for Men (SHIM) questionnaire. RESULTS: The mean patient age was approximately 59 years and the median follow-up 6 months; the compliance rate was 68%. Patients reported a significant improvement in all domains of the SHIM questionnaire after using MUSE. At the end of 6 months 74% of the patients who remained on MUSE were able to have successful vaginal intercourse. Of patients who completed the 6-month course of MUSE, half were able to have successful vaginal intercourse by the end of treatment. Most of these patients reported the recovery of spontaneous erections and required no additional erectogenic aids for successful intercourse. They had a mean SHIM score of 18.9. All 56 patients who received MUSE reported mild penile aching or urethral burning, and of these, 32% discontinued treatment. In the untreated control group, 37% regained erections sufficient for vaginal intercourse at the 6 month follow-up, with a mean SHIM score of 15.8. Of the control patients who recovered penile function, 71% were dissatisfied with the quality of their erections and sought adjuvant therapy. CONCLUSIONS: Initiating MUSE shortly after RP is safe and tolerable, and appears to shorten the recovery time to reagin erectile function. PMID- 17850386 TI - Prostate adenocarcinoma detected after high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. AB - OBJECTIVE: To review specific histological variables in patients with prostate cancer who previously had diagnoses of high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP), compared with those who had no such diagnoses. PATIENTS AND METHODS: The histological characteristics of prostate cancers which were detected after a previous diagnosis of HGPIN and/or ASAP during 1998-2005 were investigated and correlated with the biopsies from patients with prostate cancer but with no such previous diagnoses. RESULTS: HGPIN was followed by prostate cancer on repeat biopsy in 16.8% of patients, and ASAP in 26.7%. The mean age of patients with HGPIN or ASAP was higher than in those with no such diagnoses (P < 0.001). Similarly, patients with these previous diagnoses had a lower Gleason score (P = 0.017 and <0.001, respectively) and lower tumour volume variables (fewer tumour foci, P = 0.033 and 0.041, respectively) and shorter cancer (P = 0.048 and 0.030) in core biopsies than those without. CONCLUSIONS: Patients with prostate cancer who had previous biopsies with HGPIN or ASAP were older and has lower grade- and volume-cancers than those who had not. PMID- 17850387 TI - Outcomes using a fourth-generation lithotripter: a new benchmark for comparison? AB - OBJECTIVE: To evaluate the efficacy of a fourth-generation lithotripter, the Sonolith Vision (Technomed Medical Systems, Vaulx-en-Velin, France) for treating single previously untreated renal calculi, and to compare the results with the reference standard HM-3 (Dornier MedTech Europe GmbH, Wessling, Germany) in the same population originally studied by the USA Cooperative Study Group in 1986. PATIENTS AND METHODS: The Sonolith Vision uses an innovative electroconductive shock-wave generator with an elliptical reflector specially designed to give the maximum concentration of energy on the stone. We reviewed the treatment sessions from our prospectively maintained database of the first 1000 consecutive patients with urinary stone disease who were treated with the Sonolith Vision between September 2004 and March 2006. Patients with previously untreated solitary renal calculi in anatomically normal kidneys were included. The outcome was assessed by plain films for radio-opaque stones, and renal ultrasonography for radiolucent stones, at 1 and 3 months after lithotripsy; the results were analysed according to stone size and location. RESULTS: Data from 309 patients who had a complete follow-up and with 373 renal calculi that matched the above criteria were analysed. The initial fragmentation rate was 94%. The stone-free rate for stones of <10 mm was 77%, for 11-20 mm was 69% and for >20 mm was 50%. The overall stone free rate 3 months after lithotripsy was 75%. Within a month of lithotripsy, 221 patients (59%) became stone-free. Additional procedures to render patients stone free after lithotripsy were needed in only 22 cases (7%). The overall efficiency quotient was 62%. The stone-free rates for lower, upper, middle calyceal and renal pelvic calculi were 74%, 70%, 78.5% and 75%, respectively. There were no serious complications. CONCLUSIONS: When similar populations of stone formers were assessed the Sonolith Vision achieved a high success rate, comparable with that using the HM-3 machine but with lower analgesia requirements and very low re treatment rates. This method of comparison belies the commonly held view that newer lithotripters are less effective than the original spark-gap machines. PMID- 17850388 TI - A novel murine model for the study of human renal cryoablation. AB - OBJECTIVE: to develop a reproducible, non-debilitating in vivo murine model of human renal cryoablation using a standard closed argon-delivery system. MATERIALS AND METHODS: Custom engineered 2-mm conical tip cryoprobes for use on the standard argon-based cryoablation unit (Endocare, Inc. Irvine, CA, USA) were used to create small controllable iceballs (-160 degrees C) in the mouse kidney. The time to create a 4-mm cryolesion was compared using a contact vs puncture technique in 10 mice. To show consistency of the induced-freeze injury, a 4-mm iceball was created in 20 murine renal units and the time to creation and the size of the resultant cryolesion measured. To investigate lesion regression and histological changes, we created a 4-mm renal cryolesion in 28 mice and killed four each at 1, 3, 7, 14, 21, 28, and 35 days. The measured coronal cross sectional area of the cryoablation site at necroscopy was compared to the initial calculated area as a percentage. To assess renal preservation, blood urea nitrogen (BUN) and creatinine levels at 1 week after cryoablation or sham ablation was compared (10 mononephric mice in each group). RESULTS: The time to create the desired iceball was 1.9 times quicker using the puncture vs the contact technique. The mean (sd) time to forming a 4-mm iceball was 35.3 (4.8) s with a mean maximum length of the resultant post-thaw injury of 5.7 (0.5) mm and a 9% coefficient of variance. Regression analysis of the two-dimensional cross sectional coronal area of the cryolesion showed a statistically significant linear pattern of regression over time (P = 0.037) and classic histological findings. There was no significant difference in the BUN or creatinine levels in mononephric mice 1 week after cryotherapy compared with the sham-ablated controls. CONCLUSIONS: We describe a reproducible, non-debilitating, easily manipulated murine model for the study of human renal cryoablation. PMID- 17850389 TI - Protective effects of cranberries on infection-induced oxidative renal damage in a rabbit model of vesico-ureteric reflux. AB - OBJECTIVE: To evaluate the protective effects of cranberry fruit, which have known antioxidant effects, on infection-induced oxidative renal damage in a rabbit model of vesico-ureteric reflux (VUR). MATERIALS AND METHODS: In all, 36 New Zealand male rabbits were divided into five groups, with a sham operation in four rabbits serving as the control (group 1). To create unilateral VUR the roof of the left intravesical ureter was incised, and VUR confirmed 2 weeks after surgery. In all, 32 rabbits with VUR were divided into four groups; 2, VUR alone (with sterile urine); 3, a group infected with Escherichia coli; 4, with intravesical E. coli instillation but fed cranberries; and 5, intravesical E. coli instillation plus an intraperitoneal injection with melatonin group. At 3 weeks after surgery the rabbits were killed, the kidneys obtained and examined histopathologically to evaluate inflammation, fibrosis and tubular changes. Oxidative renal damage was evaluated by measuring malondialdehyde in the renal tissue. RESULTS: Grossly, the refluxing kidney was larger than the contralateral normal kidney, and the refluxing ureter was dilated and tortuous. Microscopy of tissues from the kidneys in group 3 showed apparent periglomerular mononuclear cell infiltration, tubular dilatation and atrophy, and interstitial fibrosis. The kidneys from groups 2, 4 and 5 showed mild mononuclear cell infiltration with no interstitial fibrosis. The level of malondialdehyde in the kidneys of group 3 was significantly higher than that in group 2, 4 and 5 (P < 0.05); the level in groups 4 and 5 did not differ significantly from that in group 2. CONCLUSIONS: This study shows that cranberries have an anti-inflammatory effect through their antioxidant function and might prevent infection-induced oxidative renal damage. Thus, clinically cranberries might be used as a beneficial adjuvant treatment to prevent damage due to pyelonephritis in children with VUR. PMID- 17850390 TI - A validated mouse model for orthotopic bladder cancer using transurethral tumour inoculation and bioluminescence imaging. AB - OBJECTIVES: To describe a technique for transurethral tumour inoculation, bioluminescence imaging (BLI) and validation of this approach using ex vivo magnetic resonance imaging (MRI), as a reproducible and quantifiable model of orthotopic bladder cancer is required to enable preclinical pharmacological studies of intravesically administered anticancer agents and the use of BLI provides a sensitive method to monitor tumour growth over time. MATERIALS AND METHODS: Human KU-7 bladder tumour cells were transduced with a lentiviral construct to stably express the firefly luciferase gene. These cells were then inoculated in female nude mice by intravesical instillation. BLI was performed weekly and the mice were killed after 4 weeks. Ex vivo MRI and whole-mount step sections were obtained to assess bladder tumour volume. RESULTS: KU-7 tumour cells were highly tumorigenic and were successfully inoculated in 96% of mice. After 4 weeks, all tumours were confined to the mucosa and submucosa (30 kg/m2). In patients who had achieved SSR by week 8, on-demand therapy for 2 months was started. The number of 40-mg esomeprazole tablets used per 4-wk period was recorded. RESULTS: SSR rates were lower in both the overweight and obese groups than in the control group (P < 0.001). During on-demand therapy, the mean number of tablets used per 4-wk period was lower in the control group than in either the overweight or the obese group (13.2 vs 15.3 or 16.2, P < 0.05). The failure rate of on-demand therapy increased with increasing BMI-2.4%, 5.3%, and 14.2%, respectively, for the control, overweight, and obese groups (P= 0.002). CONCLUSION: For RE-AB, a higher BMI decreases the rate of SSR after 8-wk of esomeprazole therapy, and increases the need for medication and the failure rate of on-demand therapy. PMID- 17850410 TI - FibroTest and FibroScan for the prediction of hepatitis C-related fibrosis: a systematic review of diagnostic test accuracy. AB - BACKGROUND: The accurate diagnosis of hepatitis C virus (HCV)-related fibrosis is crucial for prognostication and treatment decisions. Due to the limitations of biopsy, noninvasive alternatives including FibroTest and FibroScan have been developed. Our objective was to systematically review studies describing the accuracy of these tests for predicting HCV-related fibrosis. METHODS: Studies comparing FibroTest or FibroScan versus biopsy in HCV patients were identified via an electronic search. Random effects meta-analyses and areas under summary receiver operating characteristics curves (AUC) were examined to characterize test accuracy for significant fibrosis (F2-4) and cirrhosis. Heterogeneity was explored using meta-regression. RESULTS: Twelve studies were identified, 9 for FibroTest (N = 1,679) and 4 for FibroScan (N = 546). In heterogeneous analyses for significant fibrosis, the AUCs for FibroTest and FibroScan were 0.81 (95% CI 0.78-84) and 0.83 (0.03-1.00), respectively. At a threshold of approximately 0.60, the sensitivity and specificity of the FibroTest were 47% (35-59%) and 90% (87-92%). For FibroScan (threshold approximately 8 kPa), corresponding values were 64% (50-76%) and 87% (80-91%), respectively. Methodological quality, the length of liver biopsy specimens, and inclusion of special populations did not explain the observed heterogeneity. However, the diagnostic accuracy of both measures was associated with the prevalence of significant fibrosis and cirrhosis in the study populations. For cirrhosis, the summary AUCs for FibroTest and FibroScan were 0.90 (95% CI not calculable) and 0.95 (0.87-0.99), respectively. CONCLUSIONS: FibroTest and FibroScan have excellent utility for the identification of HCV-related cirrhosis, but lesser accuracy for earlier stages. Refinements are necessary before these tests can replace liver biopsy. PMID- 17850411 TI - Has toll-like receptor 4 been prematurely dismissed as an inflammatory bowel disease gene? Association study combined with meta-analysis shows strong evidence for association. AB - OBJECTIVES: Published association studies of the TLR4 Asp299Gly polymorphism and inflammatory bowel disease (IBD) in caucasian populations have inconsistent results. We tested two TLR4 variants for association with IBD in the New Zealand caucasian population and assessed the cumulative evidence for association of TLR4 Asp299Gly and IBD. METHODS: The TLR4 Asp299Gly and Thr399Ile polymorphisms were genotyped and tested for case-control frequency differences in a New Zealand white cohort of 389 Crohn's disease (CD) patients, 405 ulcerative colitis (UC) patients, and 416 population controls. Meta-analysis using a random effects model was performed to test whether 299Gly carriage was associated with UC, CD, or phenotypes of CD patients. RESULTS: There were no significant allele or genotype frequency differences between cases and controls or between CD phenotypes in our New Zealand data. Meta-analysis did not identify any significant associations between CD phenotypes and 299Gly carriage. However, meta-analysis demonstrated significantly higher 299Gly carrier frequencies in CD patients (odds ratio 1.45, 95% CI 1.11-1.90) and in IBD patients (odds ratio 1.36, 95% CI 1.01-1.84) compared to controls. CONCLUSIONS: The meta-analysis provides evidence that Asp299Gly is associated with CD and IBD in whites. Only the Asp299Gly polymorphism has been consistently genotyped in previous TLR4 studies with IBD patients, therefore other TLR4 variants with stronger associations with IBD may exist. Additional well-powered studies of Asp299Gly and other TLR4 variants are urgently needed. PMID- 17850412 TI - The impact of prolonged pH measurements on the diagnosis of gastroesophageal reflux disease: 4-day wireless pH studies. AB - INTRODUCTION: Prolonged, 4-day (96 h) measurement by the wireless Bravo system provides an opportunity to assess the variance, diagnostic reproducibility, and yield of 24- and 48-h pH and symptom association studies. METHOD: Retrospective analysis of 83 patients with suspected reflux symptoms undergoing wireless pH monitoring with the intention of 96-h measurement. Study periods were classified based on esophageal acid exposure, the DeMeester score (DMS), and the association of reflux events and symptoms (symptom index). The technical success of prolonged pH recording and diagnostic accuracy of 24-, 48-, and 72-h pH studies compared to the 96-h "gold standard" were assessed. RESULTS: Prolonged Bravo pH studies were possible and well tolerated in routine clinical practice. Complete 96-h recordings were available for 34/83 (41%) patients. Variation in pH measurements reduced with increasing study duration (24-h 45%vs 48-h 27%, P<0.01), but no change in reflux severity over time was observed (ANOVA, P=ns). Abnormal acid exposure was found in 7 (19%) on every test day and 21 (58%) on at least one of four test days. A diagnosis consistent with the 96-h "gold standard" was present in 22 (63%), 29 (83%), and 32 (91%) patients for 24-, 48-, and 72-h test periods, respectively, with a significant improvement of diagnostic sensitivity with study duration (P<0.01). Similar findings were present for symptom association. CONCLUSION: Increasing the duration of pH studies progressively improves measurement variance and the diagnostic reproducibility of reflux studies. Future studies must address the impact of prolonged pH studies on clinical management. PMID- 17850413 TI - Predictive and protective factors associated with upper gastrointestinal bleeding after percutaneous coronary intervention: a case-control study. AB - BACKGROUND: Hemorrhagic complications of acute coronary syndromes and percutaneous coronary intervention (PCI) are associated with increased mortality. Upper gastrointestinal (UGI) bleeding after PCI is a potential target for preventative strategies. OBJECTIVE: To evaluate the risk factors for UGI bleeding in a large cohort of contemporary PCI patients and assess the outcomes of medical and endoscopic management. METHOD: A case-control study evaluating UGI bleeding in the 30 days following PCI for stable angina and acute coronary syndromes, at one institution between 1998 and 2005. Cases were identified and outcomes assessed using linkage analysis of data from institutional PCI and endoscopy databases, statewide vital statistics and hospital discharge registries, and a detailed review of medical notes for each case and three matched controls. Analysis of the case and control groups for risk and protective factors was performed using the chi2 test with Fisher's exact P value and logistic regression. RESULTS: The incidence of UGI bleeding following PCI was 1.2% (70 of 5,673 patients). The etiologies of these bleeds were diverse. Risk factors for UGI bleeding were primary PCI (OR 27.80, 95% CI 6.28-123.05, P < 0.001), cardiac arrest (OR 6.17, 95% CI 1.82-20.84, P= 0.003), inotropic requirement (OR 5.85, 95% CI 1.98-17.27, P= 0.001), thienopyridine use before PCI (OR 2.40, 95% CI 1.04 5.53, P= 0.02), and advanced age (OR 1.08, 95% CI 1.04-1.12, P < 0.001). Proton pump inhibitor use after PCI (OR 0.08, 95% CI 0.02-0.40, P= 0.002) was accompanied by a reduced risk of UGI bleeding. Endoscopy provided therapeutic intervention in 33% of patients. There were no serious complications of endoscopy. The 30-day mortality for cases was 11.9% and 0.5% for controls (P= 0.001). CONCLUSION: UGI bleeding after PCI is relatively common and associated with increased mortality. Those undergoing PCI for acute myocardial infarction or in the presence hemodynamic instability are at highest risk. Proton pump inhibition following PCI may reduce the bleeding risk, though when UGI bleeding occurs, therapeutic endoscopy is safe. PMID- 17850414 TI - Biodegradability of naltrexone-poly(DL) lactide implants in vivo assessed under ultrasound in humans. AB - Ultrasound was used to assess the in vivo biodegradability of a sustained release poly(DL)lactide naltrexone implant in 71 persons previously treated for heroin dependence. We assessed 139 implant sites ranging from 2 to 1808 days post implant. Ultrasound assessment showed that implant tablets were initially well demarcated from each other and from the surrounding tissues. Biodegradation resulted in less demarcated tablets followed by clumping into a single mass-like structure. This mass subsequently dispersed by approximately 1201 days post implant with no implant material visualized by ultrasound. The biodegradation was also assessed by visual clinical examination and palpation of the implant site as well as patient self-report. These measures were generally well correlated with ultrasound results. Clinical assessment of the biodegradation process concluded that the implant changed from 'firm' to 'less firm' and from 'initial square edge' to 'rounded edge' tablets. Collectively, these data provide direct evidence of the in vivo absorption of the Go Medical implant over time, and its biodegradability in humans. PMID- 17850415 TI - Effects of chronic stress on nicotine-induced locomotor activity and corticosterone release in adult and adolescent rats. AB - We examined nicotine-induced locomotion and increase in corticosterone plasma levels in adolescent and adult animals exposed to chronic restraint stress. Adolescent [postnatal day (P) 28-37] and adult (P60-67) rats were restrained for 2 hours once daily for 7 days. Three days after the last exposure to stress, the animals were challenged with saline or nicotine (0.4 mg/kg subcutaneously). Nicotine-induced locomotion was recorded in an activity cage. Trunk blood samples were collected in a subset of adolescent and adult rats and plasma corticosterone levels were determined by radioimmunoassay. Exposure to stress did not affect the nicotine-induced locomotor- or corticosterone-activating effects in both ages. PMID- 17850416 TI - Long-lasting tolerance to alcohol following a history of dependence. AB - Tolerance to alcohol effects is one of the defining features of clinical alcohol dependence. Here, we hypothesized that the post-dependent state may include tolerance to sedative-hypnotic alcohol actions. To address this question, we used a recently developed animal model in which repeated cycles of alcohol intoxication and withdrawal trigger long-lasting behavioral plasticity. This animal model shares important features with the clinical condition. Animals were exposed to 7 weeks of intermittent alcohol vapor, allowed to recover for 3 weeks, and tested in protracted abstinence to exclude contributions from acute withdrawal. Post-dependent and control rats were injected with a hypnotic dose of alcohol (3 g/kg), and the loss of righting reflex (LORR) was recorded, blood alcohol levels were monitored, and the elimination rate was calculated. Post dependent animals showed a decrease in LORR. Alcohol metabolism and elimination kinetics did not differ between groups. In conclusion, a history of alcohol dependence induces long-lasting hypnotic tolerance. This process may play an important role in maintaining the dependent state. PMID- 17850417 TI - Teratogenic effects of maternal antidepressant exposure on neural substrates of drug-seeking behavior in offspring. AB - If neurotransmitter balance is upset in the developing nervous system by exposure to antidepressant drugs, structural and functional hedonic phenotypes of offspring may be affected. In order to test this hypothesis, two groups of pregnant Wistar dams were exposed to vehicle or fluoxetine by implantation on gestational day 14 of osmotic minipumps delivering 0 or 10 mg/kg/day fluoxetine for 14 days. The consequences of perinatal fluoxetine exposure on offspring conflict-exploratory behavior were quantified using the elevated plus-maze on postnatal day (PND) 30. Beginning on PND 60, the reinforcing properties of acutely administered cocaine were examined using a place conditioning procedure. Beginning on PND 90, a subset of rats were implanted with jugular catheters and allowed to acquire self-administration of cocaine in an operant environment. In support of the hedonic modulation hypothesis, perinatal fluoxetine produced a significant decline in both nucleus accumbens cell count (-9%) and serotonin transporter-like immunoreactivity in the raphe nucleus (-35%) on PND 120. In the elevated plus-maze, perinatal fluoxetine exposure decreased (-21%) overall activity. In the place conditioning trial, only the fluoxetine-treated group exhibited a significant place preference for the compartment paired previously with cocaine. In a cocaine self-administration extinction trial, there was a statistically significant increase (350%) in extinction response rate among fluoxetine-exposed offspring. These findings suggest that perinatal exposure to fluoxetine perturbs adult serotonergic neurotransmission and produces a positive hedonic shift for conditioned reinforcing effects of cocaine. PMID- 17850418 TI - Age-dependent differences in sensitivity and sensitization to cannabinoids and 'club drugs' in male adolescent and adult rats. AB - Lifelong substance abuse is often initiated during adolescence; yet, most pre clinical research in this area has been conducted in adult animals. Substantial evidence exists that the brain development that continues throughout adolescence may result in pharmacological responses that differ in a crucial manner from those of adults. The goal of this study was to evaluate age differences in motor activity following acute and repeated administration of drugs that are commonly abused by adolescents, including cocaine, Delta(9)-tetrahydrocannabinol (Delta(9) THC), and the club drugs, ketamine and 3,4-methylenedioxymethamphetamine (MDMA). Adolescent and adult male rats were injected once daily with saline or with a dose of one of the test drugs for two 5-day dosing periods, separated by a 2-day drug holiday during which they remained in their home cages. Following each injection, rats were placed in a locomotor chamber for a 20-minute session. The potencies of cocaine, ketamine and MDMA for producing motor stimulation were less in male adolescents than in male adults. Furthermore, sensitization to the club drug, ketamine, developed after repeated dosing in adults, but not adolescents. In contrast, adolescents were initially more sensitive to the stimulatory effects of low doses of Delta(9)-THC than were adults, although rapid tolerance occurred. These results suggest that adolescents are less sensitive to the acute and repeated stimulant effects of some, but not all, of the drugs that are preferentially abused by this age group. This differential sensitivity may contribute to the different patterns of use that have been noted in adolescent versus adult drug abusers. PMID- 17850419 TI - Resource use in patients with Crohn's disease treated with infliximab. AB - AIM: To estimate the impact of infliximab (IFX) on hospital resources for patients with Crohn's disease. METHODS: Resource use data for at least 1 year before (B-IFX) and after (A-IFX) infliximab administration were retrospectively collected for all patients treated with IFX at the Hospital Cabuenes (Spain). Direct costs calculated were: hospital-stays, surgeries, out-patient visits, diagnostic and laboratory tests, pharmacological treatments, and day-care hospitalization for IFX administration. RESULTS: Patients (n = 34; mean age at treatment: 43.6 years) with 9.8 and 4.3 years (B-IFX and A-IFX, respectively) had their costs estimated. Partial or complete response was achieved in 82% of patients. Total annual B-IFX costs per patient were Euro 4,464, of which 62.4% was for hospitalization, 3.1% for surgery, 8.7% for consultation visits, 16.2% for diagnostic and laboratory tests, and 9.6% for other treatments. Total annual A-IFX costs per patient were Euro 10,594; of which 6.4% was for hospitalization, 0.8% for surgery, 4.2% for consultation visits, 7.6% for diagnostic and laboratory tests, 5.5% for other treatments, and 75.5% for IFX and its administration. The primary cost item was hospitalization (Euro 2,783) during the B-IFX period as opposed to IFX itself (Euro 7,996) during the subsequent A-IFX period. CONCLUSIONS: In routine practice, IFX appears to be an effective treatment by reducing hospital-stays, but increases overall budgetary cost for patients with Crohn's disease. PMID- 17850420 TI - The role of hepatitis E virus testing in drug-induced liver injury. AB - BACKGROUND: Locally acquired hepatitis E is an emerging infection in developed countries and can be misdiagnosed as drug-induced liver injury. AIM: To study the role of hepatitis E virus (HEV) testing in drug-induced liver injury. METHODS: Retrospective review of a cohort of patients with suspected drug-induced liver injury (n = 69) and hepatitis E (n = 45). The standard criteria for drug-induced liver injury were applied. Patients with suspected drug-induced liver injury who met these criteria were retrospectively tested for HEV on stored sera taken at the time of presentation. The two cohorts were compared to determine variables that predicted either of the diagnoses. RESULTS: Forty-seven out of 69 patients had criterion-referenced drug-induced liver injury. 22/47 were HEV negative and thus had confirmed drug-induced liver injury. 19/47 were not tested for HEV, as there was no sera available from the time of presentation. 6/47 were HEV positive and thus did not have drug-induced liver injury, but had hepatitis E infection. Compared to patients with confirmed drug-induced liver injury, patients with hepatitis E were significantly more likely to be male (OR 3.09, CI 1.05-9.08); less likely to present in November and December (0.03, CI 0.01-0.52); have lower serum bilirubin (P = 0.015); and higher serum alanine aminotransferase (P < 0.001) and alanine aminotransferase/alkaline phosphatase ratio (P < 0.001). CONCLUSION: The diagnosis of drug-induced liver injury is not secure without testing for HEV. PMID- 17850421 TI - Selection bias in case-control studies on periodontitis: a systematic review. AB - In case-control studies the frequency of the exposure of interest is compared between a group of diseased subjects and a group of controls to determine whether an association exists between disease and exposure. Case-control studies are useful, but can be subject to several sources of bias if poorly conducted. Selection bias, which results in a lack of comparability between the groups being studied, is one of the most harmful types of bias. The aim of this study was to assess the information reported on case-control studies of periodontitis to identify sources of selection bias. We conducted an electronic search in PubMed, EMBASE, and Web of Science and evaluated the occurrence of sources of selection bias in case-control studies published in English during the year 2004. In relatively few studies did the authors provided information on recruitment periods for cases and controls (31.1% and 20%, respectively), sampling methods (26.7% and 31.1%, respectively), or participation rates (8.9% and 6.7%, respectively). The source of control subjects was appropriate in 15.6% of the studies, and the strategy used to select the controls was adequate in only 8.9% of the studies. It may be concluded that case-control studies on periodontitis are frequently inadequately conducted and reported. PMID- 17850423 TI - Cytokine expression pattern in compression and tension sides of the periodontal ligament during orthodontic tooth movement in humans. AB - Orthodontic tooth movement is achieved by the remodeling of periodontal ligament (PDL) and alveolar bone in response to mechanical loading and is believed to be mediated by several host mediators, such as cytokines. By means of real-time polymerase chain reaction (PCR), we studied the pattern of expression of mRNA encoding several pro- and anti-inflammatory cytokines in relation to several extracellular matrix and bone remodeling markers, in tension (T) and compression (C) sides of the PDL of human teeth subjected to rapid maxillary expansion. The PDL of normal teeth was used as a control. The results showed that both T and C sides exhibited significantly higher expression of all targets when compared with controls, except for type I collagen (COL-I) and tissue inhibitor of metalloproteinase-1 (TIMP-1) on the C side. Comparing C and T sides, the C side exhibited higher expression of tumor necrosis factor-alpha (TNF-alpha), receptor activator of nuclear factor-kappaB ligand (RANKL), and matrix metalloproteinase-1 (MMP-1), whereas the T side presented higher expression of interleukin-10 (IL 10), TIMP-1, COL-I, osteoprotegerin (OPG), and osteocalcin (OCN). The expression of transforming growth factor-beta (TGF-beta) was similar in both C and T sides. Our data demonstrate a differential expression of pro- and anti-inflammatory cytokines in compressed and stretched PDL during orthodontic tooth movement. PMID- 17850422 TI - Nerve growth factor beta/pro-nerve growth factor and their receptors in normal human oral mucosa. AB - Nerve growth factor beta (NGF-beta) and its precursor proNGF are important for the differentiation and survival of neurons and dermal keratinocytes. The aim of this study was to determine the role that NGF might play in the differentiation and wound healing of oral mucosa. Cultured normal human oral mucosal keratinocytes expressed mRNA for NGF-beta/proNGF and for their receptors TrkA and p75(NTR). Lysates from cultured oral mucosal keratinocytes did not contain detectable amounts of mature 14-kDa NGF-beta but did contain several NGF proforms with molecular weights between 32 and 114 kDa. Culture medium from oral mucosal keratinocytes contained 75 kDa proNGF. The addition of NGF-beta significantly enhanced the proliferation of oral mucosal keratinocyte cultures and in vitro scratch closure. Immunostaining of biopsies from normal oral mucosa showed the presence of proNGF in all epithelial layers. NGF staining was observed in the granular and upper spinous cell layers. TrkA immunoreactivity was detected in basal and parabasal cells, with weak to moderate staining in spinous and granular cell layers. p75(NTR) staining was seen in basal cell layers. These findings indicate that NGF-beta/proNGF have mitogenic and motogenic effects on oral mucosal keratinocytes and therefore may aid in the healing of oral wounds. Differential expression of NGF and NGF receptors throughout the epithelium suggests a role in epithelial differentiation. PMID- 17850424 TI - The adaptive response of Streptococcus mutans towards oral care products: involvement of the ClpP serine protease. AB - In the oral cavity a balanced physiological response is essential for Streptococcus mutans to survive various types of external challenges. In this study we examined the role of the ClpP serine protease in the response of S. mutans towards sodium fluoride, sodium chloride, hydrogen peroxide, and chlorhexidine. By constructing a clpP promoter-green fluorescent protein reporter strain, we showed increased fluorescence intensities under all types of stress, indicating a need for ClpP under all these challenges. We constructed a clpP knockout mutant, which proved to be more sensitive to all the challenges than the wild-type strain. This knockout strain also displayed a reduced growth rate, hyperaggregation, and increased biofilm formation. Furthermore, an increased resistance to toxic levels of hydrogen peroxide and chlorhexidine after pre incubation with sublethal levels of the corresponding compounds was found in the wild-type strain but not in the knockout mutant. In conclusion, ClpP is involved in the general stress response of S. mutans and assists the bacteria to resist killing through adaptation. PMID- 17850425 TI - Modulation of an inhibitory jaw reflex by remote noxious stimulation: effects of spatial conditioning factors. AB - In humans, inhibitory jaw reflexes can be depressed by painful stimulation of remote parts of the body. The underlying mechanisms may involve diffuse noxious inhibitory controls (DNIC). Animal experiments have shown that the neurons which may mediate DNIC show spatial encoding (i.e. their responses vary in relation to the size of the body area being stimulated). The aim of this study was to investigate whether the modulation of an inhibitory jaw reflex shows similar spatial dependency. Electromyographic recordings were made in 9 subjects, from a masseter muscle that was activated to a level equivalent to 10% of that obtained during a maximum voluntary contraction. Reflex inhibitions were evoked by electrical stimuli to the upper lip, either alone (controls) or during the application of conditioning stimuli (47 degrees C water) to the fingers, the hand, the half forearm or the whole forearm. Conditioning stimuli applied to the larger but not to the smaller areas resulted in significant modulations of the reflex. There was a significant correlation between stimulus area and reflex magnitude. These results demonstrate a spatial dependency for the modulation of an inhibitory jaw reflex by painful stimuli -- a further parallel with DNIC as studied on single neurons in animals. PMID- 17850426 TI - Influence of immigration and other factors on caries in 12- and 15-yr-old children. AB - In recent years the Valencia region has undergone mass immigration, mainly of people from eastern Europe, North Africa, and Latin America. The objective of this study was to assess the effect of immigration on caries prevalence and experience in 12- and 15-yr-old children in the Valencia region, and to relate this to other socio-economic and oral hygiene-related variables. The data were obtained from the epidemiological study of oral health carried out in the Valencia Region in 2004. The study group comprised 478, 12-yr-old children and 401, 15-yr-old children. Immigration status, age, toothbrushing frequency, and intake of cariogenic foods between meals showed significant association in a multiple linear regression model using the decayed, missing or filled teeth (DMFT) count as the dependent variable. Of all the predictive variables, the one that made the highest contribution to the model was immigration status. In a multiple logistic regression analysis with caries presence as the dependent variable, immigration status, intake of cariogenic foods, social class, and age were significantly associated with the presence of caries. As immigrant children have significantly higher caries levels than Spanish children, future public health service planning should pay attention to this risk group. PMID- 17850427 TI - Routine oral examination: clinical performance and management by general dental practitioners in primary care. AB - The aim of this clinical study was to explore the contents of routine oral examinations (ROE), carried out by Dutch general dental practitioners (GDPs), in relation to the oral health status of regularly attending patients. An observational study was performed, based on clinical case recording. Using The Data Station Project of the Dutch Dental Association as the study base, 215 GDPs were recruited, of whom 131 participated in the study. A clinical case-recording form was developed to document clinical behavior. The contents assessed concerned patient characteristics, contents of the ROE visit, diagnoses made, and clinical behavior in response to ROE findings. This study showed substantial variation in clinical behavior related to specific ROE domains, including patient history and record keeping, whereas GDPs acted consistently on other domains, such as clinical examination and recall length assessment. Furthermore, the ROE performance was more strongly associated with GDP characteristics than with patient characteristics. The mean ROE time was 10 min, and recall intervals were most frequently assigned at 6 months, irrespective of the oral condition. This study highlights a need for continuing education to promote risk-based oral screening. Further research is needed to identify factors responsible for the variation in GDP performance, just as research on clinical practice guideline implementation methods is warranted. PMID- 17850428 TI - Effects of toothbrushing on eroded dentine. AB - It is an established assumption that eroded dental hard tissues are particularly prone to toothbrush abrasion. Only a few studies have aimed to show this for dentine and, if so, disregarded the complex histological structure of this tissue. Therefore, the present study sought (i) to investigate the effects of toothbrushing on eroded dentine and (ii) to analyze how the organic matrix influences the outcome of established methods for quantifying dental hard tissue loss. The effects of brushing were investigated by optical (P-O) and mechanical (P-M) profilometry, by longitudinal microradiography (LMR), and by scanning electron microscopy (SEM). The SEM images showed that a demineralized organic layer had developed, which was unaffected by brushing. For substance loss, there was no significant difference between eroded and eroded/abraded samples. Considerable differences occurred, however, when results from the different methods were compared. P-O yielded the lowest (7.0 +/- 3.4 microm) and LMR the highest (109.8 +/- 10.7 microm) substance loss values. When the organic material was removed enzymatically, all methods gave comparable results. The results of this study do not lend support to the notion that brushing increases substance loss of eroded dentine. Profilometry was not suitable for measuring mineral loss, unless the organic material was removed. PMID- 17850429 TI - Patterns of cell death and cell cycle profiles of cultured WEHI 13 var fibroblasts exposed to eluates of composite resins used for direct and indirect restorations. AB - Previous studies have shown that in vitro exposure to single compounds released from composite resins may induce cell death. In the present study the effects of eluates from commercially available composite resins used for direct or indirect restorations were evaluated on the cell cycle progression and type of cell death of cultured WEHI 13 var fibroblasts. Cells exposed to eluates of the materials were assessed for cytotoxicity by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay for cell death, for cell cycle profiles by flow cytometry, for caspase-3 biochemically and by immunocytochemistry, and for morphological changes by fluorescence microscopy with acridine orange. The direct composite resin eluates induced extensive apoptosis, followed by secondary necrosis. This was accompanied by cell enlargement, micromultinucleation, chromatin disintegration, cell cycle arrest at different phases, and caspase-3 activation. The composites for indirect restorations were much less cytotoxic at all biological end-points investigated. The findings suggest that composite resins used for direct and indirect dental restorations differ in their cytotoxic potential and their ability to affect basic cellular functions. This underlines the impact of improved polymerization with respect to their biologic behavior. PMID- 17850430 TI - Factorial analysis of variables influencing mechanical characteristics of a single tooth implant placed in the maxilla using finite element analysis and the statistics-based Taguchi method. AB - The aim of this study was to determine the relative contribution of changes (design factors) in implant system, position, bone classification, and loading condition on the biomechanical response of a single-unit implant-supported restoration. Non-linear finite-element analysis was used to simulate the mechanical responses in an implant placed in the maxillary posterior region. The Taguchi method was employed to identify the significance of each design factor in controlling the strain/stress. Increased strain values were noted in the cortical bone with lateral force and an implant with a retaining-screw connection. Cancellous bone strain was affected primarily by bone type and increased with decreasing bone density. Implant stress was influenced mainly by implant type and position. The combined use of finite-element analysis and the Taguchi method facilitated effective evaluation of the mechanical characteristics of a single unit implant-supported restoration. Implants placed along the axis of loading exhibit improved stress/strain distribution. The reduction of lateral stress through implant placement and selective occlusal adjustment is recommended. An implant with a tapered interference fit connection performed better as a force transmission mechanism than other configurations. PMID- 17850431 TI - Hydrolytic stability of composite repair bond. AB - The hydrolytic stability of composite repairs is a desirable property. In the present study, the composite repair microtensile bond strength, failure mode distribution, and nanoleakage occurrence before and after thermocycling were evaluated. Standardized, 1-month-old composite substrates were roughened, cleaned, and randomly assigned to seven groups according to the intermediate agent applied. Resin-based, silane-based, and combined silane/adhesive coupling agents were investigated. The same resin composite as the substrate was used for repair. For each group, repaired samples were wet stored for 24 h (37 degrees C) or thermocycled (5,000 cycles, 5-55 degrees C). Failure mode and silver nitrate penetration were examined by stereomicroscopy. Intermediate agent, experimental condition, and their interaction were significant factors. Hydrophobic flowable composites resulted in statistically higher repair strengths, lower occurrence of adhesive failures, and good quality interfacial coupling without any silver uptake in both conditions. Light-curing, hydrophilic resin monomer-based intermediate agents, although not affected by thermocycling, showed a more pronounced silver penetration. The composite repair strength of a self-curing silane/adhesive agent was significantly affected by thermal stresses, despite the absence of silver uptake. A prehydrolized silane agent recorded the lowest repair strength, with minimal or no evidence of interfacial silver impregnation after thermocycling. In conclusion, flowability and hydrophobic nature can be considered important properties when selecting intermediate agents for composite repair. PMID- 17850432 TI - Early primary tooth eruption in neurofibromatosis 1 individuals. PMID- 17850433 TI - Fcgamma receptors mediate internalization of anti-Ro and anti-La autoantibodies from Sjogren's syndrome and apoptosis in human salivary gland cell line A-253. AB - BACKGROUND: The presence of serum anti-Ro and anti-La autoantibodies directed against the ribonucleoproteins Ro and La has been associated with Sjogren's syndrome (SS), an autoimmune rheumatic disease that targets salivary and lachrymal glands. There is increasing evidence of the direct involvement of autoantibodies in the pathogenesis of tissue injury and correlation of their presence with clinical manifestations in SS. The focus of this work was to explore the cellular apoptotic pathway triggered by binding and penetration of anti-Ro and anti-La autoantibodies in human salivary gland cell line A-253 and to identify the membrane receptors through which anti-Ro and anti-La could exert their effect. METHODS: Anti-Ro and anti-La autoantibodies were purified from IgG fractions, obtained from eleven healthy volunteers and patients with primary Sjogren's syndrome, using Sepharose 4B-Ro and Sepharose 4B-La affinity columns. Flow cytometry, RT-PCR, western blot and confocal microscopy analysis were used to visualize the FCgammaRI, FCgammaRII and FCgammaRIII receptors on the A-253 cell membrane. DNA laddering and western blot analysis of caspases activation were studied to evaluate in A-253 cells treated with anti-Ro and anti-La autoantibodies. RESULTS: The results yeilded the evidence of the presence of members of the Fcgamma receptors (FcgammaRs) family on the cell membrane of the human salivary gland cell line A-253. Furthermore, we demonstrated that, in the A 253 cell line, anti-Ro and anti-La autoantibodies can access the cells probably through Fcgamma receptors, and trigger apoptotis. CONCLUSIONS: We conclude that anti-Ro and anti-La autoantibodies have pathogenic effects that could depend on binding to Fcgamma receptors. PMID- 17850434 TI - Oral manifestations of systemic and cutaneous lupus erythematosus in a Venezuelan population. AB - BACKGROUND: The aim of this study was to characterize oral lesions in patients with systemic and cutaneous lupus erythematosus (LE) in a Venezuelan group. METHODS: Ninety patients with LE were studied. Oral biopsies were taken from patients who showed oral mucosal involvement. Tissue samples were investigated with histology and direct immunofluorescence techniques for the presence of immunoglobulins G, M, A and complement factor C3. RESULTS: In 90 patients with LE, 10 patients showed oral lesions related to the disease. Sixteen lesions were investigated. Oral ulcerations accompanied by white irradiating striae occurred in five patients, erythema was observed in five patients and a white homogeneous plaque in one patient. Fifteen lesions demonstrated vacuolar basal degeneration and 12 thickening of the basement membrane histologically. Direct immunofluorescence was negative in three samples. CONCLUSIONS: These findings corroborated that ulcers are not the only manifestation of LE in the oral mucosa. Clinical and histological examinations are significant as immunoproteins are not always found on the oral sample. PMID- 17850435 TI - Oral manifestation of chronic mucocutaneous candidiasis: seven case reports. AB - BACKGROUND: Chronic mucocutaneous candidiasis (CMC) is a rare disorder characterized by persistent or recurrent candidal infections of the skin, nails and mucous membranes or by a variable combination of endocrine failure as well as immunodeficiency. Oral clinicopathological features of CMC have seldom been described in detail. METHODS: Seven patients with CMC were reported in the study. The clinical and histological findings, etiological Candida species, immunological evaluation, and therapeutic pattern of oral lesions, were analyzed. RESULTS: Long-standing whitish hyperplastic and nodule-like lesions with exaggerated deep fissure were the typical and characteristic oral manifestations presented by all patients. The tongue was the most common site affected. Histologically, no obvious distinction was found between CMC and other forms of candidal infection. Abnormal proportions of T-lymphocyte subsets and positive titers of autoantibody were observed in three subjects (42.9%) and one patient (14.3%) respectively. Meanwhile, four subjects (57.1%) showed decreased albumin and increased globulin, three cases (42.9%) had high levels of ESR. But no iron deficiency was found. Candida albicans was the microorganism isolated from these patients. CONCLUSIONS: Multiple and widespread candidal infectious lesions can be observed on the oral cavity of CMC patients. Hyperplastic and nodule-like lesion with irremovable whitish patches and deep fissure are the most common oral manifestations of these patients. Dentists, otolaryngologists and pediatricians should be familiar with the clinical appearances of CMC to make an accurate diagnosis. Potential systemic disorders should be concerned to avoid the reoccurrence of oral candidiasis. PMID- 17850436 TI - Investigation of functional gene polymorphisms: IL-1B, IL-6 and TNFA in benign migratory glossitis in Brazilian individuals. AB - BACKGROUND: Benign migratory glossitis (BMG) is a very common immunological oral disease of unknown aetiology. METHODS AND SUBJECTS: Fifty-three consecutive subjects affected by BMG and 53 age- and sex-matched control subjects were genotyped for IL-1B, IL-6 and TNFA polymorphisms. Binary logistic regression models were fitted and values of P < 0.05 were considered significant. RESULTS: A significant difference in the distribution of IL-1B genotypes was observed in the group with BMG in univariate analyses (P = 0.01). The multivariate analyses showed that the CT genotype of the IL1-B gene was significantly associated with a high risk to develop BMG (P = 0.02, OR 2.76). The combined presence of IL-1beta high and intermediate producers genotypes was also associated with BMG in multivariate analyses (P = 0.01, OR 3.05). IL-6 and TNFA polymorphisms were not associated with BMG in the univariate and multivariate analyses. CONCLUSION: Our findings demonstrate that the polymorphism +3954 IL-1B is associated with an increased risk of BMG development and suggest a genetic basis for disease development. PMID- 17850437 TI - Solitary fibrous tumor of the oral cavity: the need for an extensive sampling for a correct diagnosis. AB - BACKGROUND: Solitary fibrous tumor (SFT) is an uncommon but well-characterized soft tissue tumor that was first described as a pleural lesion and now is considered ubiquitous, having been detected at many extra-pleural sites (abdominal cavity, orbit, upper respiratory tract, and oral cavity). Histologically, SFT may show wide morphological variability of both its cellular and stromal components, which may lead to incorrect diagnosis especially when dealing with small incisional biopsies. MATERIALS: We report on the clinical, morphological and immunohistochemical features of eight SFT occurring in the oral cavity. RESULTS: Microscopically all eight tumors showed widely variable morphological features in terms of cellular density and stromal architecture, thus simulating benign fibrous histiocytoma, schwannoma, hemangiopericytoma or low-grade sarcoma in distinct areas of the same lesion. Among these eight cases, five had been diagnosed as SFT, two as benign fibrous histiocytoma and one as low grade sarcoma. CONCLUSIONS: In consideration of the heterogeneous morphological appearance of SFT, inaccurate sampling of the mass may lead to misdiagnosis and inappropriate treatment. Therefore, an accurate histological examination of multiple tissue sections is advised, along with the use of appropriate immunostains. PMID- 17850438 TI - Immunohistochemical detection of phosphorylated JNK, p38 MAPK, and ERK5 in ameloblastic tumors. AB - BACKGROUND: To evaluate roles of mitogen-activated protein kinases (MAPKs) in oncogenesis and cytodifferentiation of odontogenic tumors, expression of phosphorylated JNK (p-JNK), p38 MAPK (p-p38 MAPK), and ERK5 (p-ERK5) was analyzed in ameloblastic tumors as well as in tooth germs. METHODS: Ten tooth germs, 47 ameloblastomas, and 5 malignant ameloblastic tumors were examined immunohistochemically with the antibodies against p-JNK, p-p38 MAPK, and p-ERK5. RESULTS: Immunoreactivity for p-JNK was detected in epithelial or neoplastic cells detached from the basement membrane in 7 tooth germs and 7 ameloblastomas, and the expression levels of p-JNK in ameloblastic tumors were significantly lower than that in tooth germs. Expression of p-p38 MAPK was found in epithelial or neoplastic cells in tooth germs and ameloblastic tumors except for two ameloblastomas, and increased expression was found in keratinizing cells of acanthomatous ameloblastomas. The expression level of p-p38 MAPK in ameloblastomas was significantly higher than the levels in tooth germs and malignant ameloblastic tumors. Immunoreactivity for p-ERK5 was found predominantly in epithelial or neoplastic cells near the basement membrane in tooth germs and ameloblastic tumors. The expression levels of p-ERK5 in ameloblastic tumors were slightly higher than that in tooth germs, and plexiform ameloblastomas showed significantly higher p-ERK5 expression than follicular ameloblastomas. CONCLUSION: Expression of p-JNK, p-p38 MAPK, and p-ERK5 in tooth germs and ameloblastic tumors suggests that these MAPK signaling pathways contribute to cell proliferation, differentiation, or apoptosis in both normal and neoplastic odontogenic tissues. Altered expression of these phosphorylated MAPKs in ameloblastic tumors may be involved in oncogenesis and tumor cell differentiation. PMID- 17850439 TI - Analysis of the neoplastic nature and biological potential of sporadic and nevoid basal cell carcinoma syndrome-associated keratocystic odontogenic tumor. AB - BACKGROUND: Keratocystic odontogenic tumor (KCOT), also known as odontogenic keratocyst, is a benign cystic neoplasm, which may be associated with nevoid basal cell carcinoma syndrome (NBCCS) and if it does, will occur as multiple cystic lesions. KCOT is locally destructive despite its bland histological features. However, the neoplastic nature of KCOT is not well established. Heparanase is an endo-d-glucuronidase enzyme that specifically cleaves heparan sulfate (HS) and the increase of its level in tumors promotes invasion, angiogenesis, and metastasis. METHODS: To investigate the neoplastic character of KCOT, we studied the localization patterns of heparanase in KCOT, focusing on the differences between sporadic and NBCCS-associated KCOTs, by immunohistochemistry and in situ hybridization. To compare the expression pattern of these cysts with non-tumorous odontogenic developmental cyst, dentigerous cyst was included. RESULTS: All the odontogenic cysts showed positive immunoreaction for heparanase protein in various intensities. The expression pattern of heparanase gene corresponded to that of protein expression. Interestingly, intense gene and protein expressions were observed in KCOT associated with NBCCS compared with sporadic ones and dentigerous cyst. CONCLUSIONS: The results implied that heparanase expression may be correlated with the neoplastic properties of KCOT, particularly in NBCCS-associated cases. PMID- 17850440 TI - Oromandibular limb hypogenesis syndrome, type IIA, hypoglossia-hypodactylia: a case report. AB - A patient with oromandibular limb hypogenesis syndrome, type IIA hypoglossia hypodactylia, is reported. The features essential for the diagnosis of this congenital defect include a reduction in tongue size (microglossia), micrognathic mandible and limb abnormalities of varying severity. Parents and the other sibling were normal. Past medical history for exposure of the mother to drugs during pregnancy was positive. PMID- 17850441 TI - Island of salivary gland in adipose tissue: a report of three cases. AB - Although uncommon, many variants of lipomatous lesions in or around salivary glands have been reported in the literature. We report a series of three such cases in the minor salivary gland region. The first case (oral floor) is a well circumscribed lipocytic lesion admixed with glandular components (mucous acini, serous demilunes and ducts). The second case (alveolar mucosa) is a diffuse lipomatous proliferation with entrapped salivary glandular elements, muscles and blood vessels. The third case (palate) is similar to the first case but the gland is located at the periphery of the lesion. The purpose of the article was to report these three lesions and discuss in relation to other pertaining lipomatous lesions (sialolipoma, lipoadenoma, lipomatosis, lipometaplasia in pleomorphic adenoma and infiltrating lipoma). PMID- 17850442 TI - How to name it: a rare case of odontogenic cyst. AB - Odontogenic cysts and tumors are well-recognized entities to the specialist oral pathologist and they seldom pose problems in differential diagnosis. This paper deals with an aggressive cystic lesion in the maxilla of a 65-year-old male that was characterized by a large radiographically multilocular lesion and a multicystic pattern microscopically. The categorization of this lesion was complicated by the presence of features suggestive of both glandular odontogenic cyst and cystic ameloblastoma with aggressive histologic phenotypes. PMID- 17850443 TI - Calcineurin inhibitor-associated oral inflammatory polyps after transplantation. AB - Calcineurin inhibitors (cyclosporine and tacrolimus) have been used as the mainstay immunosuppressive therapy for solid organ and hematopoietic cell transplantations (HCT) to prevent allograft rejection and for prophylaxis and treatment of the chronic graft-versus-host disease. Adverse effects of these drugs include nephrotoxicity, hepatotoxicity, neurotoxicity, hypertension and gingival hyperplasia. Association of oral non-gingival soft tissue hyperplasia with calcineurin inhibitor therapy has only recently been recognized and is thought to occur infrequently. We present four cases of oral non-gingival inflammatory fibro-vascular hyperplasias attributed to the use of calcineurin inhibitors following solid organ transplantation and HCT. These lesions interfere with function and must be differentiated from other oral lesions, and therefore should be surgically excised. PMID- 17850445 TI - Cellular and molecular susceptibility determinants for periodontitis. PMID- 17850446 TI - Human variability in innate immunity. PMID- 17850448 TI - B cells in periodontitis: friends or enemies? PMID- 17850449 TI - T-cell phenotype as a risk factor for periodontal disease. PMID- 17850450 TI - Interference with immune-cell-mediated bone resorption in periodontal disease. PMID- 17850447 TI - Oral mucosal dendritic cells and periodontitis: many sides of the same coin with new twists. PMID- 17850451 TI - Mendelian forms of periodontitis. PMID- 17850452 TI - Cytokines and inflammatory factors regulating immunoglobulin production in aggressive periodontitis. PMID- 17850453 TI - Diabetes-enhanced inflammation and apoptosis: impact on periodontal pathosis. PMID- 17850454 TI - Cross-susceptibility between periodontal disease and type 2 diabetes mellitus: an immunobiological perspective. PMID- 17850455 TI - Control of inflammation and periodontitis. PMID- 17850456 TI - Chronic stress and neural function: accounting for sex and age. AB - Cognitive responses to stress follow the temporally dependent pattern originally established by Selye (1) wherein short-term stressors elicit adaptive responses whereas continued stress (chronic) results in maladaptive changes--deleterious effects on physiological systems and impaired cognition. However, this pattern for cognitive effects appears to apply to only half the population (males) and, more specifically, to young, adult males. Females show different cognitive responses to stress. In contrast to impaired cognition in males after chronic stress, female rodents show enhanced performance on the same memory tasks after the same stress. Not only cognition, but anxiety, shows sex-dependent changes following chronic stress--stress is anxiolytic in males and anxiogenic in females. Moreover, behavioral responses to chronic stress are different in developing as well as aging subjects (both sexes) as compared to adults. In aged rats, chronic stress enhances recognition memory in both sexes, does not alter spatial memory, and anxiety effects are opposite to young adults. When pregnant dams are exposed to chronic stress, at adulthood the offspring display yet different consequences of stress on anxiety and cognition, and, in contrast to adulthood when the behavioral effects of stress are reversible, prenatal stress effects appear enduring. Changing levels of estradiol in the sexes over the lifespan appear to contribute to the differences in response to stress. Thus, theories of stress dependent modulations in CNS function--developed solely in male models, focused on peripheral physiological processes and tested in adults- may require revision when applied to a more diverse population (age- and sex wise) at least in relation to the neural functions of cognition and anxiety. Moreover, these results suggest that other stressors and neural functions should be investigated to determine whether age, sex and gonadal hormones also have an impact. PMID- 17850457 TI - Increased caloric intake on a fat-rich diet: role of ovarian steroids and galanin in the medial preoptic and paraventricular nuclei and anterior pituitary of female rats. AB - Previous studies in male rats have demonstrated that the orexigenic peptide galanin (GAL), in neurones of the anterior parvocellular region of the paraventricular nucleus (aPVN) projecting to the median eminence (ME), is stimulated by consumption of a high-fat diet and may have a role in the hyperphagia induced by fat. In addition to confirming this relationship in female rats and distinguishing the aPVN-ME from other hypothalamic areas, the present study identified two additional extra-hypothalamic sites where GAL is stimulated by dietary fat in females but not males. These sites were the medial preoptic nucleus (MPN), located immediately rostral to the aPVN, and the anterior pituitary (AP). The involvement of ovarian steroids, oestradiol (E(2)) and progesterone (PROG), in this phenomenon was suggested by an observed increase in circulating levels of these hormones and GAL in MPN and AP with fat consumption and an attenuation of this effect on GAL in ovariectomised (OVX) rats. Furthermore, in the same four areas affected by dietary fat, levels of GAL mRNA and peptide immunoreactivity were stimulated by E(2) and further by PROG replacement in E(2)-primed OVX rats and were higher in females compared to males. Because both GAL and PROG stimulate feeding, their increase on a fat-rich diet may have functional consequences in females, possibly contributing to the increased caloric intake induced by dietary fat. This is supported by the findings that PROG administration in E(2)-primed OVX rats reverses the inhibitory effect of E(2) on total caloric intake while increasing voluntary fat ingestion, and that female rats with higher GAL exhibit increased preference for fat compared to males. Thus, ovarian steroids may function together with GAL in a neurocircuit, involving the MPN, aPVN, ME and AP, which coordinate feeding behaviour with reproductive function to promote consumption of a fat-rich diet at times of increased energy demand. PMID- 17850458 TI - Effects of organisational oestradiol on adult immunoreactive oestrogen receptors (alpha and beta) in the male mouse brain. AB - Steroid hormones act on developing neural circuits that regulate the hypothalamic pituitary-gonadal axis and are involved in hormone-sensitive behaviours. To test the hypothesis that developmental exposure to oestradiol (E(2)) organises the quantity of adult oestrogen receptors (ERalpha and ERbeta), we used male mice with a targeted mutation of the aromatase enzyme gene (ArKO) and their wild-type (WT) littermates. These mice are unable to aromatise testosterone to E(2), but still express both ERalpha and beta. To evaluate adult responsiveness to E(2), gonadectomised males were implanted with Silastic capsules containing E(2), or an empty implant, 5 days prior to sacrifice. Immunoreactivity for ERalpha and ERbeta was quantified in the caudal ventromedial nucleus (VMN) and the medial preoptic area (POA). Regardless of genotype, adult treatment with E(2) reduced ERalpha immunoreactive (ir) and ERbeta-ir cell numbers in the POA, as well as ERbeta-ir, but not ERalpha-ir, cell numbers in the VMN. Genotype, and thus endogenous exposure to E(2), produced opposite effects on ER expression in the two brain areas. In the VMN, ArKO males had more ERalpha-ir and ERbeta-ir cells than did WT males. In the POA, ArKO males had fewer ERalpha-ir and ERbeta-ir cells than did WT males. Thus, numbers of immunoreactive neurones containing both ERs in the adult ArKO male were enhanced in the POA, but decreased in the VMN, and most likely these patterns were established during the developmental critical period. Furthermore, although both ERalpha and beta-ir cell numbers are altered by the disruption of the aromatase gene, ERbeta is altered in a more robust and region specific manner. PMID- 17850459 TI - Reproductive experience and expression of dopamine D(2) receptor mRNA: a possible mechanism for reduced prolactin secretion in primiparous rats. AB - Reproductive experience (i.e. pregnancy and lactation) leads to reduced levels of circulating prolactin in both women and rats. Stimulation of prolactin secretion by dopamine antagonists is also blunted following reproductive experience in both species. Whereas a parity-induced reduction in haloperidol-stimulated prolactin secretion is evident in ovariectomised rats, it is unknown whether a similar attenuation of prolactin secretion is present in reproductively experienced, cycling pro-oestrous rats. The present study examined this possibility. Moreover, to determine possible mechanisms involved in parity-mediated changes in prolactin secretion, both dopamine utilisation within the arcuate nucleus/median eminence and expression of dopamine D(2) receptor mRNA (short and long forms) in the anterior pituitary were measured across the afternoon of pro-oestrous in reproductively experience and inexperienced females. Prolactin secretion was lower on the afternoon of pro-oestrous in primiparous females compared to age matched, nulliparous controls. In addition, haloperidol-stimulated prolactin secretion was reduced in ovariectomised, reproductively experienced females. Although no differences in dopamine utilisation were observed as a function of reproductive experience, parity did affect the expression of both forms of D(2) receptor mRNA in the anterior pituitary. Compared with nulliparous controls, primiparous females had increased D(2 long) mRNA expression at 12.00 h on pro oestrous as well as increased D(2 short) mRNA expression at 14.00 h. Because the ratio of D(2 long)/D(2 short) can significantly effect lactotroph proliferation and prolactin secretion, a shift in relative expression of the two D(2) receptor isoforms within the anterior pituitary of parous females may help account for the reduction in prolactin secretion that occurs following reproductive experience. PMID- 17850460 TI - Changes of expression of genes related to the activity of the gonadotrophin releasing hormone pulse generator in young versus middle-aged male rats. AB - In females, it is well established that changes in the expression of neurotransmitters and peptides regulating the activity of the gonadotrophin releasing hormone (GnRH) pulse generator are altered during ageing. By contrast, little is known about whether those age-related changes also occur in males. Therefore, we designed an animal study with orchidectomised young and middle-aged male rats to investigate changes in luteinising hormone (LH) secretion profiles and changes in the mRNA expression of genes regulating the activity of the GnRH pulse generator. Our results demonstrate that middle-aged rats exhibit lower serum LH levels and relatively fewer LH pulses with attenuated amplitude compared to young animals. Furthermore, upon ageing, GnRH mRNA expression is up-regulated in the preoptic area and the septum where GnRH neurones reside. Analysis of mRNA levels of glutamate decarboxylase (GAD) enzymes revealed that GAD(65) and GAD(67) mRNA expression increased in the mediobasal hypothalamus (MBH) and that GAD(67) mRNA levels decreased in the suprachiasmatic nucleus. In addition, we observed an age-related increase of oestrogen receptor (ER)alpha mRNA in the MBH, and both ERalpha and ERbeta mRNA expression was up-regulated in the pituitary of middle aged rats compared to young animals. Taken together, our data support the existence of a male 'andropause' that is, like the menopause in females, accompanied by changes in neurotransmitter and hormone receptor expression that are involved in regulating the function of the GnRH pulse generator. PMID- 17850461 TI - Expression of ovarian steroid hormone receptors in tuberoinfundibular dopaminergic neurones during pregnancy and lactation. AB - During late-pregnancy, tuberoinfundibular dopaminergic (TIDA) neurones, a critical component of the negative-feedback loop regulating prolactin secretion, become unresponsive to the stimulatory effects of prolactin. The change in TIDA responsiveness to prolactin at this time results in a decrease in dopamine secretion and a prolactin surge. As the onset of parturition and the antepartum prolactin surge depend on the withdrawal of progesterone in the presence of oestrogen, it is likely that ovarian steroid hormones mediate this change in TIDA responsiveness. To determine whether ovarian steroids can directly modulate TIDA activity, and whether changes of receptor numbers might contribute to overall steroid-regulation of these neurones, we investigated the level of oestrogen receptor alpha (ERalpha) and progesterone receptor (PR) expression within TIDA neurones during pregnancy and lactation. Animals were sacrificed on dioestrous, days 12, 19 and 21 of pregnancy and day 5 of lactation, and the proportion of TIDA neurones expressing ERalpha or PR, as well as the total number of PR expressing cells within the arcuate nucleus, was determined. Approximately 75% and 55% of tyrosine hydroxylase neurones expressed ERalpha and PR, respectively. Levels of steroid receptor expression within TIDA neurones remained fairly constant, except for an increase in ERalpha on days 12 and 19 of pregnancy compared to dioestrous and lactation day 5. The presence of steroid receptors on TIDA neurones during pregnancy and lactation supports the concept of a direct effect of steroid hormones on these neurones at this time. Thus, steroid hormones may directly act on TIDA neurones to regulate maternal prolactin secretion. The relatively stable level of expression during late pregnancy suggests that a shift in steroid receptor expression during late pregnancy does not contribute to the change in TIDA responsiveness to prolactin at this time. PMID- 17850462 TI - Mapping brain c-Fos immunoreactivity after insulin-induced voluntary lard intake: insulin- and lard-associated patterns. AB - In addition to the inhibitory role of central insulin on food intake, insulin also acts to promote lard intake. We investigated the neural pathways involved in this facet of insulin action. Insulin or saline was infused into either the superior mesenteric or right external jugular veins of streptozotocin-diabetic rodents with elevated steady-state circulating corticosterone concentrations. After postsurgical recovery, rats were offered the choice of chow or lard to eat. Irrespective of the site of venous infusion, insulin increased lard and decreased chow intake. After 4 days, lard was removed for 8 h. On return for 1 h, only insulin infused into the superior mesenteric vein resulted in lard intake. This facilitated distinction between the effects of circulating insulin concentrations (similar in the two insulin-infused groups) and lard ingestion on the patterns of c-Fos(+) cells in the brain, termed insulin- and lard-associated patterns, respectively. Insulin-associated changes in c-Fos(+) cell numbers were evident in the arcuate nucleus, bed nucleus of the stria terminalis and substantia nigra pars compacta, concomitant with elevated leptin levels and reduced chow intake. Lard-associated changes in c-Fos(+) cell numbers were observed in the nucleus of the tractus solitarius, lateral parabrachial nucleus, central nucleus of the amygdala, ventral tegmental area, nucleus accumbens shell and the prefrontal cortex, and were associated with lower levels of triglycerides and free fatty acids. The anterior paraventricular thalamic nucleus exhibited both patterns. These data collectively fit into a framework for food intake and reward and provide targets for pharmacological manipulation to influence the choice of food intake. PMID- 17850463 TI - Neuroendocrine regulation of fluid and electrolyte balance by ovarian steroids: contributions from central oestrogen receptors. AB - Like other hormonally mediated mechanisms, maintenance of body fluid osmolality requires integrated responses from multiple signals at various tissue locales, a large number of which are open to modulation by circulating endocrine factors including the ovarian steroid, oestrogens (E(2)). However, the precise mechanism and the site of action of E(2) in regulating fluid osmolality are not properly understood. More importantly, the biological significance of this action is not clear and the physiological circumstances in which this modulation is engaged remain incomplete. The demonstration of oestrogen receptors (ER) in neural tissues that bear no direct relation to reproduction led us to examine and characterise the expression of ER in brain nuclei that are critical for the maintenance of fluid osmolality. In the rat, ERbeta is prominently expressed in the vasopressin magnocellular neuroendocrine cells of the hypothalamus, whereas ERalpha is localised extensively in the sensory circumventricular organ neurones in the basal forebrain. These nuclei are the primary brain sites that are engaged in defense of fluid perturbation, thus providing a neuroendocrine basis for oestrogenic influence on body fluid regulation. Plasticity in receptor expression that accompanies fluid disturbances at these central loci suggests the functional importance of the receptors and implicates E(2) as one of the fluid regulating hormones in water homeostasis. PMID- 17850464 TI - Oestrogen and progesterone reduce lipopolysaccharide-induced expression of tumour necrosis factor-alpha and interleukin-18 in midbrain astrocytes. AB - Besides microglia, astrocytes exert an important regulatory function in the initiation and control of neuro-inflammatory processes in the central nervous system. Clinical and experimental data suggest that sex steroids are neuroprotective and that neurological/neurodegenerative disorders display sex specific characteristics. Astroglia is known to respond to toxic stimuli by secretion of distinct pro-inflammatory/apoptotic cytokines. In the present study, we investigated the influence of oestrogen and progesterone on the expression of the cytokines tumour necrosis factor (TNF)-alpha and interleukin (IL)-18 in primary astrocytes obtained from neonatal mouse midbrain and cerebral cortex after the stimulation with lipopolysaccharides (LPS). LPS strongly induced the expression of TNF-alpha in astrocytes from both brain regions and IL-18 in those from midbrain. Oestrogen significantly attenuated LPS-induced TNF-alpha expression in the midbrain glia but not in the cortex glia. Combined treatment with oestrogen and progesterone together diminished LPS-induced IL-18 expression in the midbrain completely. Both steroid effects could be specifically antagonised by the steroid hormone receptor antagonists ICI 182 780 and mifepristone. We conclude that neuroprotective oestrogen and progesterone effects in the midbrain might be in part the consequence of a reduced pro-inflammatory response of astroglia. PMID- 17850465 TI - Androgen receptor expression in the levator ani muscle of male mice. AB - The spinal nucleus of the bulbocavernosus (SNB) is a sexually dimorphic group of motoneurones that innervates the bulbocavernosus (BC) and levator ani (LA), skeletal muscles that attach to the base of the penis. In many species, including mice, rats and hamsters, the LA and BC have been found to be highly responsive to androgen and, in rats, these muscles mediate several effects of androgen on the SNB system. However, characterising the SNB system in mice is important because of the availability of genetic models in this species. In the present study, we examined AR expression in skeletal muscles of C57/BlJ6 adult male mice using immunoblotting and immunocytochemistry, comparing the BC/LA to the androgen unresponsive extensor digitorum longus (EDL). We found similar differences in AR expression for these muscles in the mouse as previously reported for rats. In mice, the BC/LA contains more AR protein than does the EDL. At the cellular level, the LA contains a higher percentage of AR positive myonuclei and fibroblasts than does the EDL. Finally, AR expression is enriched at the neuromuscular junction of mouse LA fibres. The increased expression of AR in the LA compared to the EDL in both muscle fibres and fibroblasts indicates that each cell type may critically mediate androgen action on the SNB system in mice. PMID- 17850466 TI - Autoreactive T-cell responses: new technology in pursuit of an old nemesis. PMID- 17850468 TI - Autonomic function testing in children and adolescents with diabetes mellitus. AB - Cardiac autonomic neuropathy (CAN) is a common complication in type 1 diabetes mellitus (T1DM) and associated with an increased mortality. Early detection of CAN would be desirable for a better individual risk stratification. The aim of this study was to determine whether autonomic dysfunction can be diagnosed in young patients with a recent history of T1DM. Autonomic function was assessed in 20 pediatric patients with T1DM, aged 10-19 yr, and a control group of 136 non diabetic patients using four cardiorespiratory reflexes: heart rate and blood pressure response in standing position, deep breathing, and Valsalva maneuver. Furthermore, power spectral analyses of the low- and high-frequency band of heart rate variability (HRV) and baroreflex sensitivity (BRS) were tested with the non invasive Task force monitor (CNSystems, Graz, Austria). Cardiorespiratory reflexes were pathologic for at least one item in 75% of the diabetic and 60% in the healthy control group. A reduced BRS was always combined with abnormal HRV. We found this pattern in 30% of diabetic patients and never in the control group. In patients with impaired BRS, mean hemoglobin A1c (HbA1c) was 7.7% and duration of diabetes 6.5 yr. This did not differ from the overall value of the diabetic group: HbA1c level 8.4% and diabetes duration 7.3 yr. In conclusion, signs of autonomic dysfunction are not uncommon in an early stage of diabetes in young patients. Classical cardiorespiratory reflexes seem to be less specific than HRV and BRS as testing methods. PMID- 17850467 TI - Protein microarray analysis as a tool for monitoring cellular autoreactivity in type 1 diabetes patients and their relatives. AB - BACKGROUND: Autoreactive T cells have a crucial role in type 1 diabetes (T1D) pathogenesis. OBJECTIVES: The aim of our study was to monitor the in vitro production of cytokines by peripheral blood mononuclear cells (PBMCs) after stimulation with diabetogenic autoantigens. SUBJECTS: Ten T1D patients (tested at the time of diagnosis and 6 and 12 months later), 10 first-degree relatives of the T1D patients, and 10 controls underwent the study. METHODS: PBMCs were stimulated with glutamic acid decarboxylase 65 (GAD65) amino acids (a.a.) 247 279, 509-528, and 524-543; proinsulin a.a. 9-23; and tyrosine phosphatase (islet antigen-2)/R2 a.a. 853-872. Interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, IL-13, interferon (IFN)-gamma, tumor necrosis factor beta, transforming growth factor beta1, and granulocyte colony-stimulating factor (GCSF) were analyzed by protein microarray. RESULTS: Differences in cytokine(s) poststimulatory and mainly in basal production were observed in all groups. The most prominent findings were in controls, the higher basal levels of IL-2, IL-4, IL-5, IL-13, and GCSF were observed when compared with relatives (p < 0.05, for all). After stimulation in controls, there was a significant decrease in IL-2, IL-13, GCSF, and IFN-gamma (p < 0.05, for all). The group of relatives was the most variable in poststimulatory production. A strong correlation between cytokines production was found but groups differed in this aspect. CONCLUSION: By multiplex analysis, it may be possible, for example, to define the risk immunological response pattern among relatives or to monitor the immune response in patients on immune modulation therapy. PMID- 17850469 TI - Tobacco, alcohol, and illicit drug use in adolescents with diabetes mellitus. AB - BACKGROUND: Substance abuse in adolescents with diabetes mellitus (DM) is associated with the development of acute and chronic complications. OBJECTIVE: To determine the prevalence of alcohol, tobacco, and illicit drug consumption in adolescents with DM and compare it with the prevalence in a large contemporary control (C) group. METHODS: Adolescents with and without DM, who were attending 8th-12th grades, answered a structured written questionnaire, which evaluates the voluntary declaration of tobacco, alcohol, and illicit drug consumption. Subjects with DM were recruited from free diabetes camps or public hospitals (n = 193). The C group was obtained from a nationwide study of prevalence of substance abuse (n = 58,489). For illicit drugs (marijuana, cocaine, or cocaine sulfate), results are shown as life prevalence (ever used the substance). For alcohol and tobacco, results are shown as last month prevalence (the substance was used during the last month). RESULTS: Adolescents with DM showed a lower last month prevalence of tobacco and alcohol consumption than C (27.7 vs. 39.0%, p < 0.01 and 30.1 vs. 39.2%, p < 0.01, respectively). DM group had a lower life prevalence rate of illicit drugs than C group (9.6 vs. 22.2%, respectively; p < 0.01). A lower prevalence of tobacco, alcohol, and illicit drug use in DM group compared with C group was observed in grades 8, 9, and 10. However, a similar frequency of consumption was observed in 11th and 12th grades. CONCLUSION: Compared with healthy youth, DM patients use less tobacco, alcohol, and illicit drugs during the first years of adolescence but not later. PMID- 17850470 TI - Can the metabolic syndrome identify children with insulin resistance? AB - OBJECTIVE: The metabolic syndrome is associated with insulin resistance in adults. We defined pediatric metabolic syndrome using criteria analogous to Adult Treatment Panel III. The purpose of this study was to determine whether these criteria are reliable for insulin resistance in children. RESEARCH DESIGN AND METHODS: Out of 167 children (6.7 +/- 3 yr), 73 overweight [body mass index (BMI) > 95 percentile], 41 at risk of overweight (BMI > 85 < 95 percentile), and 53 normal-weight (BMI < 85 percentile) children matched for sex and age were examined. The results for waist circumference, blood pressure, oral glucose tolerance test, C-reactive protein, adiponectin, insulin, and lipids were obtained. RESULTS: There was a comparable prevalence of the metabolic syndrome in both sexes. The prevalence of the metabolic syndrome was 11.3% [95% confidence interval (CI) 6.56-16.19%] among the whole group and 21.9% (95% CI 12.24-31.0%) among overweight children. Waist circumference >75 percentile 53.2% (95% CI 45.73 60.86%) and low high-density lipoprotein 27.5% (95% CI 20.77-34.32%) were common in this sample. Compared with patients without any component of the metabolic syndrome, homeostasis model assessment insulin resistance (HOMA-IR) for patients with one through four components was higher (beta = 0.6, 95% CI 0.4-0.7, p < 0.0001, R(2) = 0.185). A logistic regression analysis using the metabolic syndrome as the dependent variable showed that HOMA-IR (odds ratio 1.52, 95% CI 1.2-2.0, p = 0.007) was the only independent risk factor for the metabolic syndrome, adjusted for age and sex. CONCLUSIONS: The importance of insulin resistance in the metabolic syndrome is supported by the results of logistic regression analysis. Early identification of children may be useful to predict future cardiovascular disease and type 2 diabetes. PMID- 17850471 TI - Parental preference of prandial insulin aspart compared with preprandial human insulin in a basal-bolus scheme with NPH insulin in a 12-wk crossover study of preschool children with type 1 diabetes. AB - OBJECTIVES: Preprandial insulin injection in preschool children is complicated by irregular eating habits. Postprandial injection of rapid-acting insulin analogs such as insulin aspart (IAsp) offers the convenience of adjusting insulin dose to match food consumed. This trial compared safety and efficacy - including parental treatment satisfaction - of two basal-bolus regimens [IAsp plus Neutral Protein Hagedorn (NPH) insulin vs. regular human insulin (HI) plus NPH] in preschool children with type 1 diabetes. METHODS: This study is a randomized, 12-wk, crossover trial comparing IAsp and regular HI in 26 children (17 boys and 9 girls; age: 2.4-6.9 yr). Regular HI was injected 30 min before and IAsp after or shortly before meals. Treatment satisfaction was assessed by a modified version of the WHO Diabetes Treatment Satisfaction Questionnaire (DTSQ-M). RESULTS: Glycemic control for IAsp treatment was not different from that for regular HI treatment as assessed by mean postprandial blood glucose increment (IAsp vs. regular HI: 2.0 vs. 1.6 mmol/L), fructosamine (300 vs. 302 micromol/L), and hemoglobin A(1c) (HbA(1c)) (7.7 vs. 7.6%). The relative risk of hypoglycemia was not significantly different [relative risk for IAsp/regular HI (95% CI): 1.06 (0.96-1.17), p = 0.225]. Mean total daily insulin dose (0.7 U/kg) remained constant throughout the trial with both treatments. The DTSQ-M score tended to be better for IAsp and reached statistical significance regarding the parental satisfaction with continuing IAsp treatment (p < 0.05). CONCLUSION: In preschool children, a basal-bolus treatment scheme with postprandial IAsp as bolus insulin was equally effective and safe compared with preprandial regular HI, although the parents showed a preference for the IAsp treatment. PMID- 17850472 TI - The Environmental Determinants of Diabetes in the Young (TEDDY) study: study design. AB - The primary objective of this multicenter, multinational, epidemiological study is the identification of infectious agents, dietary factors, or other environmental exposures that are associated with increased risk of autoimmunity and type 1 diabetes mellitus (T1DM). Factors affecting specific phenotypic manifestations such as early age of onset or rate of progression or with protection from the development of T1DM will also be identified. The Environmental Determinants of Diabetes in the Young (TEDDY) is an observational cohort study in which newborns who are younger than 4 months and have high-risk human leukocyte antigen alleles in the general population or are first-degree relatives (FDRs) of patients affected with T1DM will be enrolled. Six clinical centers in the USA and Europe will screen 361,588 newborns, of which it is anticipated that 17,804 will be eligible for enrollment with just over 7,800 followed. Recruitment will occur over 5 yr, with children being followed to the age of 15 yr. Identification of such factors will lead to a better understanding of disease pathogenesis and result in new strategies to prevent, delay, or reverse T1DM. PMID- 17850473 TI - The metabolic syndrome in children and adolescents - an IDF consensus report. PMID- 17850474 TI - Navigating pathways affecting type 1 diabetic kidney disease. PMID- 17850475 TI - Nutritional management in childhood and adolescent diabetes. PMID- 17850476 TI - Psychological care of children and adolescents with diabetes. PMID- 17850477 TI - Phagocytic cells. PMID- 17850478 TI - Phagocytosis in mosquito immune responses. AB - Anopheles mosquitoes are the only vectors of human malaria parasites. Mosquito parasite interactions are critical for disease transmission and therefore are a potential target for malaria control strategies. Mosquitoes mount potent immune responses that efficiently limit proliferation of a variety of infectious agents, including microbial pathogens and malaria parasites. The recent completion of the Anopheles gambiae genome sequencing project combined with the development of the powerful RNA interference-based gene silencing helped to identify major players of the immune defenses and uncovered evolutionarily conserved mechanisms in the anti-bacterial and anti-Plasmodium responses. The anti-bacterial responses are based on phagocytosis at early steps of infections, followed, several hours later, by the synthesis of anti-microbial peptides. The principal regulators of anti-parasitic responses are predominantly synthesized by the mosquito blood cells; however, the exact molecular mechanisms of parasite killing remain unclear. Several regulators of phagocytosis are also required for efficient parasite killing. Here, we summarize our current knowledge of the anti-bacterial and anti-parasitic responses, with the particular emphasis on the role of phagocytosis in mosquito immunity. PMID- 17850479 TI - Lipid signaling and the modulation of surface charge during phagocytosis. AB - Phagocytosis is an important component of innate and adaptive immunity. The formation of phagosomes and the subsequent maturation that capacitates them for pathogen elimination and antigen presentation are complex processes that involve signal transduction, cytoskeletal reorganization, and membrane remodeling. Lipids are increasingly appreciated to play a crucial role in these events. Sphingolipids, cholesterol, and glycerophospholipids, notably the phosphoinositides, are required for the segregation of signaling microdomains and for the generation of second messengers. They are also instrumental in the remodeling of the actin cytoskeleton and in directing membrane traffic. They accomplish these feats by congregating into liquid-ordered domains, by generating active metabolites that activate receptors, and by recruiting and anchoring specific protein ligands to the membrane, often altering their conformation and catalytic activity. A less appreciated role of acidic phospholipids is their contribution to the negative surface charge of the inner leaflet of the plasmalemma. The unique negativity of the inner aspect of the plasma membrane serves to attract and anchor key signaling and effector molecules that are required to initiate phagosome formation. Conversely, the loss of charge that accompanies phospholipid metabolism as phagosomes seal facilitates the dissociation of proteins and the termination of signaling and cytoskeleton assembly. In this manner, lipids provide a binary electrostatic switch to control phagocytosis. PMID- 17850480 TI - Mycobacterium tuberculosis and the environment within the phagosome. AB - Once across the barrier of the epithelium, macrophages constitute the primary defense against microbial invasion. For most microbes, the acidic, hydrolytically competent environment of the phagolysosome is sufficient to kill them. Despite our understanding of the trafficking events that regulate phagosome maturation, our appreciation of the lumenal environment within the phagosome is only now becoming elucidated through real-time functional assays. The assays quantify pH change, phagosome/lysosome fusion, proteolysis, lipolysis, and beta-galactosidase activity. This information is particularly important for understanding pathogens that successfully parasitize the endosomal/lysosomal continuum. Mycobacterium tuberculosis infects macrophages through arresting the normal maturation process of the phagosome, retaining its vacuole at pH 6.4 with many of the characteristics of an early endosome. Current studies are focusing on the transcriptional response of the bacterium to the changing environment in the macrophage phagosome. Manipulation of these environmental cues, such as preventing the pH drop to pH 6.4 with concanamycin A, abrogates the majority of the transcriptional response in the bacterium, showing that pH is the dominant signal that the bacterium senses and responds to. These approaches represent our ongoing attempts to unravel the discourse that takes place between the pathogen and its host cell. PMID- 17850481 TI - Salmonella sensing of anti-microbial mechanisms to promote survival within macrophages. AB - Salmonella enterica is a facultative intracellular pathogen that replicates within macrophages. The interaction of this pathogen with mammalian cells is a complex process involving hundreds of bacterial products that are sensed by and alter mammalian hosts. Numerous bacterial genes and their protein products have been identified that are required for Salmonella to resist killing by host innate immunity and to modify host processes. Many of these genes are regulated by a specific bacterial sensor, the PhoQ protein, which responds to the acidified phagosome environment. PhoQ is a sensor histidine kinase, which when activated in vivo within acidified macrophage phagosomes, regulates cell surface modifications that promote resistance to antimicrobial peptides and oxidative stress, alter the phagosome to promote intracellular survival, and reduce innate immune recognition. In this review, we discuss mechanisms by which Salmonella interacts with macrophages and focus in detail on recent reports describing the role of antimicrobial peptides and pH in PhoQ activation. PMID- 17850482 TI - Unveiling pathways used by Leishmania amazonensis amastigotes to subvert macrophage function. AB - This article provides a summary and discussion of properties of Leishmania amazonensis-loaded mouse macrophages. It illustrates how high-throughput analysis is expected to contribute to deciphering features displayed by macrophages when they are subverted as host cells for replicating Leishmania amastigotes. Firstly, we discuss features of mouse mononuclear phagocytes in steady-state conditions, including the phagocytosis of apoptotic cells. Secondly, we discuss results from ongoing investigations aimed at characterizing transcriptional signatures displayed by BALB/c mouse bone marrow-derived macrophages housing replicating L. amazonensis amastigotes. After a brief presentation on the feasibility of high throughput microscopy relying on our robust culture system, we share some perspectives on the perpetuation of L. amazonensis in their hosts. Within this latter context, a novel question is formulated and its relevance is discussed: do the Leishmania amastigotes that persist within the mammalian dermis reach a non replicating developmental stage? If so, is this developmental stage the only one displaying the features required for further development as promastigotes within the sand fly gut lumen? PMID- 17850483 TI - Collaboration between the innate immune receptors dectin-1, TLRs, and Nods. AB - Microbes are complex and present a wide variety of structures that phagocytes may recognize using innate immune receptors. Recognition triggers anti-microbial killing mechanisms and production of inflammatory cytokines and chemokines that orchestrate host defense. As a general rule, no single receptor is likely to be the sole mediator of activation of protective immune responses. Recent studies highlight the importance of collaboration between Toll-like receptors, the nucleotide oligomerization domain (Nod) proteins, and dectin-1 in regulating inflammatory responses. Studies on the molecular mechanisms of cross-talk and synergy between these receptors provide a framework in which to understand the importance of having multiple receptors recognize individual microbes. PMID- 17850484 TI - How human neutrophils kill and degrade microbes: an integrated view. AB - Neutrophils constitute the dominant cell in the circulation that mediates the earliest innate immune human responses to infection. The morbidity and mortality from infection rise dramatically in patients with quantitative or qualitative neutrophil defects, providing clinical confirmation of the important role of normal neutrophils for human health. Neutrophil-dependent anti-microbial activity against ingested microbes represents the collaboration of multiple agents, including those prefabricated during granulocyte development in the bone marrow and those generated de novo following neutrophil activation. Furthermore, neutrophils cooperate with extracellular agents as well as other immune cells to optimally kill and degrade invading microbes. This brief review focuses attention on two examples of the integrated nature of neutrophil-mediated anti-microbial action within the phagosome. The importance and complexity of myeloperoxidase mediated events illustrate a collaboration of anti-microbial responses that are endogenous to the neutrophil, whereas the synergy between the phagocyte NADPH (nicotinamide adenine dinucleotide phosphate) oxidase and plasma-derived group IIA phospholipase A(2) exemplifies the collective effects of the neutrophil with an exogenous factor to achieve degradation of ingested staphylococci. PMID- 17850485 TI - To activate or not to activate: distinct strategies used by Helicobacter pylori and Francisella tularensis to modulate the NADPH oxidase and survive in human neutrophils. AB - Neutrophils accumulate rapidly at sites of infection, and the ability of these cells to phagocytose and kill microorganisms is an essential component of the innate immune response. Relatively few microbial pathogens are able to evade neutrophil killing. Herein, we describe the novel strategies used by Helicobacter pylori and Francisella tularensis to disrupt neutrophil function, with a focus on assembly and activation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. PMID- 17850487 TI - Phagocytosis and antigen presentation in dendritic cells. AB - Like macrophages and neutrophils, dendritic cells (DCs) are considered professional phagocytes. Even if the three cell types phagocytose parasites, bacteria, cell debris, or even intact cells very efficiently, the functional outcomes of the phagocytic event are quite different. Macrophages and neutrophils scavenge and destroy phagocytosed particles, a critical step in innate immunity. DCs, in contrast, have developed means to 'preserve' useful information from the ingested particles that serve to initiate adaptive immune responses. Thus, both phagosomal degradation and acidification are much lower in DCs than in macrophages or neutrophils. Reduced degradation results in the conservation of antigenic peptides and in their increased presentation on major histocompatibility complex class I and II molecules. In this article, we review the mechanisms that control this delicate equilibrium between phagosomal degradation/cytotoxicity and antigen presentation in the different families of phagocytes. PMID- 17850486 TI - Dendritic cell subsets in health and disease. AB - The dendritic cell (DC) system of antigen-presenting cells controls immunity and tolerance. DCs initiate and regulate immune responses in a manner that depends on signals they receive from microbes and their cellular environment. They allow the immune system to make qualitatively distinct responses against different microbial infections. DCs are composed of subsets that express different microbial receptors and express different surface molecules and cytokines. Our studies lead us to propose that interstitial (dermal) DCs preferentially activate humoral immunity, whereas Langerhans cells preferentially induce cellular immunity. Alterations of the DC system result in diseases such as autoimmunity, allergy, and cancer. Conversely, DCs can be exploited for vaccination, and novel vaccines that directly target DCs in vivo are being designed. PMID- 17850488 TI - Complement receptors CD21 and CD35 in humoral immunity. AB - The complement system is a family of proteins that is involved in both innate and adaptive immunity. Complement receptors CD21 and CD35, which recognize activated products of C3 and C4, are predominantly expressed on B cells and follicular dendritic cells (FDCs) in the mouse. In this review, we focus on the role of FDC expressed CD21 and CD35 in humoral immunity. They are the principle receptors for uptake and retention of immune complexes. In their absence, memory B-cell survival is markedly impaired. This is likely because of the lack of antigen but could also reflect a role for complement C3d ligand. How antigen is transported to FDCs remains an open question. In recent unpublished work using multiphoton intravital imaging, we found that small protein antigens presented in the lymph drain rapidly into B-cell follicles and are taken up by FDCs in a complement dependent manner. PMID- 17850490 TI - Innate immunity, macrophage activation, and atherosclerosis. AB - Inflammation underpins the development of atherosclerosis. Initiation and progression of vascular inflammation involves a complex cellular network, with macrophages as major contributors. Activated macrophages produce proinflammatory mediators, bridge innate and adaptive immunity, regulate lipid retention, and participate directly in vascular repair and remodeling. Recent efforts to elucidate molecular mechanisms involved in the regulation of vascular inflammation in atherosclerosis have implicated several families of innate immune recognition receptors in inflammatory activation during the course of this disease. This article reviews our current understanding of innate immune recognition receptors, signaling pathways, and putative ligands implicated in activation of macrophages in the disease. In its final section, we propose a model for the role of macrophages in bridging inflammation and atherosclerosis from the perspective of innate immune recognition and activation. PMID- 17850493 TI - The evidence-based practice mentor: a promising strategy for implementing and sustaining EBP in healthcare systems. PMID- 17850489 TI - Mycobacterium tuberculosis, macrophages, and the innate immune response: does common variation matter? AB - Despite the discovery of the tuberculosis (TB) bacillus over 100 years ago and the availability of effective drugs for over 50 years, there remain a number of formidable challenges for controlling Mycobacterium tuberculosis (MTb). Understanding the genetic and immunologic factors that influence human susceptibility could lead to novel insights for vaccine development as well as diagnostic advances to target treatment to those who are at risk for developing active disease. Although a series of studies over the past 50 years suggests that host genetics influences resistance to TB, a comprehensive understanding of which genes and variants are associated with susceptibility is only partially understood. In this article, we review recent advances in our understanding of human variation of the immune system and its effects on macrophage function and influence on MTb susceptibility. We emphasize recent discoveries in human genetic studies and correlate these findings with efforts to understand how these variants alter the molecular and cellular functions that regulate the macrophage response to MTb. PMID- 17850494 TI - Managerial leadership for nurses' use of research evidence: an integrative review of the literature. AB - BACKGROUND: Integration of research evidence into clinical nursing practice is essential for the delivery of high-quality nursing care. Leadership behaviours of nurse managers and administrators have been identified as important to support research use and evidence-based practice. Yet minimal evidence exists indicating what constitutes effective nursing leadership for this purpose, or what kinds of interventions help leaders to successfully influence research-based care. AIMS: (1) To describe leadership activities of nurse managers that influence nurses' use of research evidence; and (2) to identify interventions aimed at supporting nurse managers to influence research use in clinical nursing practice. METHODS: A search of electronic databases was conducted for studies on behaviours or activities of nurse managers/administrators and the use of research evidence by nurses. Sifting, screening, and quality assessments were done by two reviewers. Results were synthesized by study type (quantitative and qualitative) and reported. RESULTS: Twelve studies met inclusion criteria (eight quantitative, four qualitative). Three activities were found in quantitative studies that influenced nurses' use of research: managerial support, policy revisions, and auditing. Qualitative studies showed organizational issues as barriers to managers' abilities to affect research use, while role modeling and valuing research facilitated research use. Four studies, one of which was experimental, included an intervention to support managers, but all had insufficient information about leadership development. CONCLUSIONS: To date, important descriptive work highlights the strategic role managers have in research transfer. Both facilitative and regulatory activities appear to be necessary for managers to influence research use. These findings have important implications for evolving theoretical models describing factors that affect the process of research utilization. It is time to move the science forward and test a hypothesis linking leadership to outcomes. Qualitative methods are essential for understanding the process of leadership for research transfer. PMID- 17850495 TI - Illuminating the processes of knowledge transfer in nursing. AB - RATIONALE: Over the past 10 years, there has been a propensity to translate research findings and evidence into clinical practice, and concepts such as knowledge transfer, research dissemination, research utilization, and evidence based practice have been described in the nursing literature. AIM: This manuscript shows a selective review of the definitions and utilization of these concepts and offers a perspective on their interrelationships by indicating how knowledge transfer processes are the basis of all the concepts under review. FINDINGS: Definitions and utilization of knowledge transfer in the literature have been influenced by educational and social perspectives and indicate two important processes that are rooted in the mechanisms of research dissemination, research utilization, and evidence-based practice. These processes refer to a cognitive and an interpersonal dimension. Knowledge transfer underlies a process involving cognitive resources as well as an interpersonal process where the knowledge is transferred between individuals or groups of individuals. CONCLUSION AND IMPLICATIONS: This manuscript can contribute to our understanding of the theoretical foundations linking these concepts and these processes by comparing and contrasting them. It also shows the value and empirical importance of the cognitive and interpersonal processes of knowledge transfer by which research findings and evidence can be successfully translated and implemented into the nursing clinical practice. PMID- 17850496 TI - Public health decision-makers' informational needs and preferences for receiving research evidence. AB - OBJECTIVES: The purpose of this study was to identify decision-makers' preferences for the transfer and exchange of research knowledge. This article is focused on how the participants define evidence-based decision-making and their preferences for receiving research evidence to integrate into the decision-making process. METHODS: Semistructured interviews were conducted with a purposive sample of 16 Ontario public health decision-makers from six Ontario public health units in this fundamental qualitative descriptive study. The sample included nine program managers, six directors, and one Medical Officer of Health. Participants were asked to define the term evidence-based decision-making and identify preferred research dissemination strategies. The interviews were audio-taped, transcribed verbatim, and coded for emerging concepts. RESULTS: Participants defined evidence-based decision-making as a process whereby multiple sources of information were consulted before making a decision concerning the provision of services. To facilitate integration of research evidence into the decision-making process, public health administrators appreciate receiving, in both electronic and hard copy, systematic reviews, executive summaries of research, and clear statements of implications for practice from health service researchers. CONCLUSIONS: Although consensus exists among participants concerning the definition of evidence based public health decision-making, ongoing efforts are required to continue to promote the use of research evidence in program planning and public health policy. It is also important to continue to improve the ease with which public health decision-makers access systematic reviews, as well as to ensure the relevance and applicability of the results to the practice setting. PMID- 17850503 TI - Regulating melanosome transfer: who's driving the bus? PMID- 17850497 TI - Teaching EBP: part 2 - making sense of Clinical Practice Guidelines. PMID- 17850504 TI - Melanoma senescence: HDAC1 in focus. PMID- 17850505 TI - Potent p53-independent tumor suppressor activity of ARF in melanoma-genesis. PMID- 17850506 TI - The HOG-GLI face of melanoma. PMID- 17850507 TI - Detection of melanoma cells in sentinel lymph nodes by PCR is not yet ready for prime time. PMID- 17850508 TI - Vitiligo puzzle: the pieces fall in place. AB - Over the years, the role of biochemical, immunological, genetic, and other biological aspects in the pathogenesis of vitiligo has been studied. So far, no convincing model describing the interplay of these contributing factors has been formulated. Based on existing research, we propose that vitiligo has a multi factorial etiology, characterized by multiple steps, but always involving an increase of external or internal phenol/catechol concentration, serving as a preferred surrogate substrate of tyrosinase, competing with its physiological substrate tyrosine. The conversion of these substrates into reactive quinones is reinforced by a disturbed redox balance (increasing hydrogen peroxide). Such reactive quinones can be covalently bound to the catalytic centre of tyrosinase (haptenation). This could give rise to a new antigen, carried by Langerhans cells to the regional lymph node, stimulating the proliferation of cytotoxic T cells. However, the activation of such cytotoxic cells is only a first step in skin melanocyte killing, which also depends on a shift in the balance between immune defence and tolerance, e.g. resulting from a decrease in properly functioning T regulatory cells. With this new model, based on a synthesis of several of the existing theories, in mind, the external and internal factors involved in the etiopathogenesis of vitiligo are reviewed, against the background of reported clinical data, experimental studies and existing and potential new therapies. A similar complex mechanism may also lead to some other autoimmune diseases. PMID- 17850509 TI - Neurogenic dysregulation, oxidative stress, autoimmunity, and melanocytorrhagy in vitiligo: can they be interconnected? AB - Several hypotheses have been proposed to explain vitiligo, including the neural theory, impaired redux status, autoimmunity, and more recently melanocytorrhagy arising from defective cell-cell adhesion. It is most likely that the loss of melanocytes in vitiligo arises through a combination of pathogenic mechanisms that act in concert. Here, we discuss the potential interconnection of several mechanisms that are likely to operate. These include the alteration of melanocyte specific factors by reactive oxygen species to produce neo-antigens and the role of hypoxia and oxidative stress in antigen presentation and the auto-immune destruction of melanocytes. PMID- 17850510 TI - MEK mediates in vitro neural transdifferentiation of the adult newt retinal pigment epithelium cells: Is FGF2 an induction factor? AB - Adult newts can regenerate their entire retinas through transdifferentiation of the retinal pigment epithelium (RPE) cells. As yet, however, underlying molecular mechanisms remain virtually unknown. On the other hand, in embryonic/larval vertebrates, an MEK [mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK) kinase] pathway activated by fibroblast growth factor-2 (FGF2) is suggested to be involved in the induction of transdifferentiation of the RPE into a neural retina. Therefore, we examined using culture systems whether the FGF2/MEK pathway is also involved in the adult newt RPE transdifferentiation. Here we show that the adult newt RPE cells can switch to neural cells expressing pan-retinal-neuron (PRN) markers such as acetylated tubulin, and that an MEK pathway is essential for the induction of this process, whereas FGF2 seems an unlikely primary induction factor. In addition, we show by immunohistochemistry that the PRN markers are not expressed until the 1-3 cells thick regenerating retina, which contains retinal progenitor cells, appears. Our current results suggest that the activation of an MEK pathway in RPE cells might be involved in the induction process of retinal regeneration in the adult newt, however if this is the case, we must assume complementary mechanisms that repress the MEK-mediated misexpression of PRN markers in the initial process of transdifferentiation. PMID- 17850511 TI - Melanocyte-keratinocyte interaction induces calcium signalling and melanin transfer to keratinocytes. AB - Physical contact between melanocytes and keratinocytes is a prerequisite for melanosome transfer to occur, but cellular signals induced during or after contact are not fully understood. Herein, it is shown that interactions between melanocyte and keratinocyte plasma membranes induced a transient intracellular calcium signal in keratinocytes that was required for pigment transfer. This intracellular calcium signal occurred due to release of calcium from intracellular stores. Pigment transfer observed in melanocyte-keratinocyte co cultures was inhibited when intracellular calcium in keratinocytes was chelated. We propose that a 'ligand-receptor' type interaction exists between melanocytes and keratinocytes that triggers intracellular calcium signalling in keratinocytes and mediates melanin transfer. PMID- 17850512 TI - The melanocytorrhagic hypothesis of vitiligo tested on pigmented, stressed, reconstructed epidermis. AB - Common generalized vitiligo is an acquired depigmenting disorder characterized by a chronic and progressive loss of melanocytes from the epidermis and hair follicles. We previously proposed a new theory that vitiligo involves the chronic detachment and transepidermal loss of melanocytes caused by autoimmune, neural and impaired redox mechanisms associated with mechanical trauma. In this study, we reconstructed epidermis on dead de-epidermized dermis with normal and/or non segmental non-lesional vitiligo (NSV) cells and tested catecholamines or sera or hydrogen peroxide. Under unstressed conditions, the number of melanocytes located in the basal layer was significantly lower in reconstructs made with melanocytes from non-lesional NSV skin and normal keratinocytes compared with controls made with autologous normal melanocytes. The number of non-lesional NSV melanocytes was even lower in reconstructs made with keratinocytes from non-lesional NSV skin. Epinephrine and H(2)O(2) could trigger the transepidermal loss of normal and vitiligo melanocytes. Some sera induced melanocyte detachment but without any clear correlation with disease activity in the donors. In conclusion, our results are the first step to obtaining a reproducible melanocytorrhagic model in vitro with some of the stressors investigated. They support the hypothesis that NSV melanocytes have an intrinsic defect, which limits their adhesion in a reconstructed epidermis, with an enhancer effect of the vitiligo keratinocyte milieu. PMID- 17850513 TI - A three-dimensional model of mammalian tyrosinase active site accounting for loss of function mutations. AB - Tyrosinases are the first and rate-limiting enzymes in the synthesis of melanin pigments responsible for colouring hair, skin and eyes. Mutation of tyrosinases often decreases melanin production resulting in albinism, but the effects are not always understood at the molecular level. Homology modelling of mouse tyrosinase based on recently published crystal structures of non-mammalian tyrosinases provides an active site model accounting for loss-of-function mutations. According to the model, the copper-binding histidines are located in a helix bundle comprising four densely packed helices. A loop containing residues M374, S375 and V377 connects the CuA and CuB centres, with the peptide oxygens of M374 and V377 serving as hydrogen acceptors for the NH-groups of the imidazole rings of the copper-binding His367 and His180. Therefore, this loop is essential for the stability of the active site architecture. A double substitution (374)MS(375) --> (374)GG(375) or a single M374G mutation lead to a local perturbation of the protein matrix at the active site affecting the orientation of the H367 side chain, that may be unable to bind CuB reliably, resulting in loss of activity. The model also accounts for loss of function in two naturally occurring albino mutations, S380P and V393F. The hydroxyl group in S380 contributes to the correct orientation of M374, and the substitution of V393 for a bulkier phenylalanine sterically impedes correct side chain packing at the active site. Therefore, our model explains the mechanistic necessity for conservation of not only active site histidines but also adjacent amino acids in tyrosinase. PMID- 17850514 TI - Vitiligo-associated multiple autoimmune disease is not associated with genetic variation in AIRE. PMID- 17850515 TI - Association of catalase T/C exon 9 and glutathione peroxidase codon 200 polymorphisms in relation to their activities and oxidative stress with vitiligo susceptibility in Gujarat population. PMID- 17850519 TI - Commentary: a progress report on AHRQ's Effective Health Care Program. PMID- 17850520 TI - The performance of performance measurement. PMID- 17850521 TI - Mortality of Department of Veterans Affairs patients undergoing coronary revascularization in private sector hospitals. AB - OBJECTIVE: A limitation of studies comparing outcomes of Veterans Affairs (VA) and private sector hospitals is uncertainty about the methods of accounting for risk factors in VA populations. This study estimates whether use of VA services is a marker for increased risk by comparing outcomes of VA users and other patients undergoing coronary revascularization in private sector hospitals. DATA SOURCES: Males 67 years and older undergoing coronary artery bypass graft (CABG; n=687,936) surgery or percutaneous coronary intervention (PCI; n=664,124) during 1996-2002 were identified from Medicare administrative data. Patients using VA services during the 2 years preceding the Medicare admission were identified using VA administrative files. STUDY DESIGN: Thirty-, 90-, and 365-day mortality were compared in patients who did and did not use VA services, adjusting for demographic and clinical risk factors using generalized estimating equations and propensity score analysis. RESULTS: Adjusted mortality after CABG was higher (p<.001) in VA users compared with nonusers at 30, 90, and 365 days: odds ratio (OR)=1.07 (95 percent confidence interval [CI], 1.03-1.11), 1.07 (95 percent CI, 1.04-1.10), and 1.09 (95 percent CI, 1.06-1.12), respectively. For PCI, mortality at 30 and 90 days was similar (p>.05) for VA users and nonusers, but was higher at 365 days (OR=1.09; 95 percent CI, 1.06-1.12). The increased risk of death in VA users was limited to patients with service-connected disabilities or low incomes. Odds of death for VA users were slightly lower using samples matched by propensity scores. CONCLUSIONS: A small difference in risk-adjusted outcomes for VA users and nonusers undergoing revascularization in private sector hospitals was found. This difference reflects unmeasured severity in VA users undergoing revascularization in private sector hospitals. PMID- 17850522 TI - The influence of staffing characteristics on quality of care in nursing homes. AB - OBJECTIVE: The influence staffing levels, turnover, worker stability, and agency staff had on quality of care in nursing homes was examined. DATA SOURCES/STUDY SETTING: Staffing characteristics came from a survey of nursing homes (N=1,071) conducted in 2003. The staffing characteristics were collected for Nurse Aides, Licensed Practical Nurses, and Registered Nurses. Fourteen quality indicators came from the Nursing Home Compare website report card and nursing home organizational characteristics came from the Online Survey, Certification, and Recording system. STUDY DESIGN: One index of quality (the outcome) was created by combining the 14 quality indicators using exploratory factor analysis. We used regression analyses to assess the effect of the four staffing characteristics for each of the three types of nursing staff on this quality index in addition to individual analyses for each of the 14 quality indicators. The effect of organizational characteristics as well as the markets in which they operated on outcomes was examined. We examined a number of different model specifications. PRINCIPAL FINDINGS: Quality of care was influenced, to some degree, by all of these staffing characteristics. However, the estimated interaction effects indicated that achieving higher quality was dependent on having more than one favorable staffing characteristic--the effect of quality was larger than the sum of the independent effects of each favorable staffing characteristic. CONCLUSIONS: Our results indicate that staff characteristics such as turnover, staffing levels, worker stability, and agency staff should be addressed simultaneously to improve the quality of nursing homes. PMID- 17850524 TI - Time allocation in primary care office visits. AB - OBJECTIVES: To use an innovative videotape analysis method to examine how clinic time was spent during elderly patients' visits to primary care physicians. Secondary objectives were to identify the factors that influence time allocations. DATA SOURCES: A convenience sample of 392 videotapes of routine office visits conducted between 1998 and 2000 from multiple primary care practices in the United States, supplemented by patient and physician surveys. RESEARCH DESIGN: Videotaped visits were examined for visit length and time devoted to specific topics--a novel approach to study time allocation. A survival analysis model analyzed the effects of patient, physician, and physician practice setting on how clinic time was spent. PRINCIPAL FINDINGS: Very limited amount of time was dedicated to specific topics in office visits. The median visit length was 15.7 minutes covering a median of six topics. About 5 minutes were spent on the longest topic whereas the remaining topics each received 1.1 minutes. While time spent by patient and physician on a topic responded to many factors, length of the visit overall varied little even when contents of visits varied widely. Macro factors associated with each site had more influence on visit and topic length than the nature of the problem patients presented. CONCLUSIONS: Many topics compete for visit time, resulting in small amount of time being spent on each topic. A highly regimented schedule might interfere with having sufficient time for patients with complex or multiple problems. Efforts to improve the quality of care need to recognize the time pressure on both patients and physicians, the effects of financial incentives, and the time costs of improving patient-physician interactions. PMID- 17850523 TI - A systematic review of measures of end-of-life care and its outcomes. AB - OBJECTIVE: To identify psychometrically sound measures of outcomes in end-of-life care and to characterize their use in intervention studies. DATA SOURCES: English language articles from 1990 to November 2005 describing measures with published psychometric data and intervention studies of end-of-life care. STUDY DESIGN: Systematic review of end-of-life care literature. EXTRACTION METHODS: Two reviewers organized identified measures into 10 major domains. Eight reviewers extracted and characterized measures from intervention studies. PRINCIPAL FINDINGS: Of 24,423 citations, we extracted 200 articles that described 261 measures, accepting 99 measures. In addition to 35 measures recommended in a prior systematic review, we identified an additional 64 measures of the end-of life experience. The most robust measures were in the areas of symptoms, quality of life, and satisfaction; significant gaps existed in continuity of care, advance care planning, spirituality, and caregiver well-being. We also reviewed 84 intervention studies in which 135 patient-centered outcomes were assessed by 97 separate measures. Of these, 80 were used only once and only eight measures were used in more than two studies. CONCLUSIONS: In general, most measures have not undergone rigorous development and testing. Measure development in end-of life care should focus on areas with identified gaps, and testing should be done to facilitate comparability across the care settings, populations, and clinical conditions. Intervention research should use robust measures that adhere to these standards. PMID- 17850525 TI - Factors associated with the income distribution of full-time physicians: a quantile regression approach. AB - OBJECTIVE: Physician income is generally high, but quite variable; hence, physicians have divergent perspectives regarding health policy initiatives and market reforms that could affect their incomes. We investigated factors underlying the distribution of income within the physician population. DATA SOURCES: Full-time physicians (N=10,777) from the restricted version of the 1996 1997 Community Tracking Study Physician Survey (CTS-PS), 1996 Area Resource File, and 1996 health maintenance organization penetration data. STUDY DESIGN: We conducted separate analyses for primary care physicians (PCPs) and specialists. We employed least square and quantile regression models to examine factors associated with physician incomes at the mean and at various points of the income distribution, respectively. We accounted for the complex survey design for the CTS-PS data using appropriate weighted procedures and explored endogeneity using an instrumental variables method. PRINCIPAL FINDINGS: We detected widespread and subtle effects of many variables on physician incomes at different points (10th, 25th, 75th, and 90th percentiles) in the distribution that were undetected when employing regression estimations focusing on only the means or medians. Our findings show that the effects of managed care penetration are demonstrable at the mean of specialist incomes, but are more pronounced at higher levels. Conversely, a gender gap in earnings occurs at all levels of income of both PCPs and specialists, but is more pronounced at lower income levels. CONCLUSIONS: The quantile regression technique offers an analytical tool to evaluate policy effects beyond the means. A longitudinal application of this approach may enable health policy makers to identify winners and losers among segments of the physician workforce and assess how market dynamics and health policy initiatives affect the overall physician income distribution over various time intervals. PMID- 17850526 TI - The effect of three-tier formulary adoption on medication continuation and spending among elderly retirees. AB - OBJECTIVE: To assess the effect of three-tier formulary adoption on medication continuation and spending among elderly members of retiree health plans. DATA SOURCES: Pharmacy claims and enrollment data on elderly members of four retiree plans that adopted a three-tier formulary over the period July 1999 through December 2002 and two comparison plans that maintained a two-tier formulary during this period. STUDY DESIGN: We used a quasi-experimental design to compare the experience of enrollees in intervention and comparison plans. We used propensity score methods to match intervention and comparison users of each drug class and plan. We estimated repeated measures regression models for each class/plan combination for medication continuation and monthly plan, enrollee, and total spending. We estimated logit models of the probability of nonpersistent use, medication discontinuation, and medication changes. DATA COLLECTION/EXTRACTION METHODS: We used pharmacy claims to create person-level drug utilization and spending files for the year before and year after three-tier adoption. PRINCIPAL FINDINGS: Three-tier formulary adoption resulted in shifting of costs from plan to enrollee, with relatively small effects on medication continuation. Although implementation had little effect on continuation on average, a small minority of patients were more likely to have gaps in use and discontinue use relative to comparison patients. CONCLUSIONS: Moderate cost sharing increases from three-tier formulary adoption had little effect on medication continuation among elderly enrolled in retiree health plans with relatively generous drug coverage. PMID- 17850527 TI - Cost-effectiveness of diabetes case management for low-income populations. AB - OBJECTIVE: To evaluate the cost-effectiveness of Project Dulce, a culturally specific diabetes case management and self-management training program, in four cohorts defined by insurance status. DATA SOURCES/STUDY SETTING: Clinical and cost data on 3,893 persons with diabetes participating in Project Dulce were used as inputs into a diabetes simulation model. STUDY DESIGN: The Center for Outcomes Research Diabetes Model, a published, peer-reviewed and validated simulation model of diabetes, was used to evaluate life expectancy, quality-adjusted life expectancy (QALY), cumulative incidence of complications and direct medical costs over patient lifetimes (40-year time horizon) from a third-party payer perspective. Cohort characteristics, treatment effects, and case management costs were derived using a difference in difference design comparing data from the Project Dulce program to a cohort of historical controls. Long-term costs were derived from published U.S. sources. Costs and clinical benefits were discounted at 3.0 percent per annum. Sensitivity analyses were performed. PRINCIPAL FINDINGS: Incremental cost-effectiveness ratios of $10,141, $24,584, $44,941, and $69,587 per QALY gained were estimated for Project Dulce participants versus control in the uninsured, County Medical Services, Medi-Cal, and commercial insurance cohorts, respectively. CONCLUSIONS: The Project Dulce diabetes case management program was associated with cost-effective improvements in quality adjusted life expectancy and decreased incidence of diabetes-related complications over patient lifetimes. Diabetes case management may be particularly cost effective for low-income populations. PMID- 17850528 TI - Public savings from the prevention of unintended pregnancy: a cost analysis of family planning services in California. AB - OBJECTIVE: To assess the short-term economic savings associated with the prevention of unintended pregnancies through California's Medicaid family planning demonstration project. DATA SOURCES: Secondary data from health and social service programs available to pregnant or parenting women at or below 200 percent of the federal poverty level in California in 2002 and data on the quantity and type of contraceptives dispensed to clients of California's 1115 Federal Medicaid demonstration project. STUDY DESIGN: The cost of providing publicly funded family planning services was compared with an estimate of public savings resulting from the prevention of unintended pregnancies. DATA COLLECTION: To estimate costs and participation rates in each health and social service program, we examined published program reports, government budgetary data, analyses conducted by federal and state level program managers, and calculations from national datasets. FINDINGS: The unintended pregnancies averted by California's family planning demonstration project in 2002 would have incurred $1.1 billion in public expenditures within 2 years and $2.2 billion within 5 years, significantly more than the $403.8 million spent on the project. Each dollar spent generated savings of $2.76 within 2 years and $5.33 within 5 years. CONCLUSIONS: The California 1115 Medicaid family planning demonstration project resulted in significant public cost savings. The cost of the project was substantially less than the public sector health and social service costs which would have occurred in its absence. PMID- 17850529 TI - Medicaid markets and pediatric patient safety in hospitals. AB - OBJECTIVE: To examine the association of Medicaid market characteristics to potentially preventable adverse medical events for hospitalized children, controlling for patient- and hospital-level factors. DATA SOURCES/STUDY SETTING: Two carefully selected Agency for Healthcare Research and Quality (AHRQ) pediatric patient safety indicators (decubitus ulcers and laceration) are analyzed using the new pediatric-specific, risk-adjusting, patient safety algorithm from the AHRQ. All pediatric hospital discharges for patients age 0-17 in Florida, New York, and Wisconsin, and at risk of any of these two patient safety events, are examined for the years 1999-2001 (N=859,922). STUDY DESIGN: Logistic regression on the relevant pool of discharges estimates the probability an individual patient experiences one of the two PSI events. DATA EXTRACTION METHODS: Pediatric discharges from the 1999 to 2001 State Inpatient Databases (SIDs) from the AHRQ Healthcare Cost and Utilization Project, merged with hospital-level data from the American Hospital Association's Annual Survey, Medicaid data obtained from the Centers for Medicare and Medicaid Services and state Medicaid offices, and private and Medicaid managed care enrollment data obtained from InterStudy, are used in the estimations. PRINCIPAL FINDINGS: At the market level, patients in markets in which Medicaid payers face relatively little competition are more likely to experience a patient safety event (odds ratio [OR]=1.602), while patients in markets in which hospitals face relatively little competition are less likely to experience an adverse event (OR=0.686). At the patient-discharge and hospital levels, Medicaid characteristics are not significantly associated with the incidence of a pediatric patient safety event. CONCLUSIONS: Our analysis offers additional insights to previous work and suggests a new factor--the Medicaid-payer market--as relevant to the issue of pediatric patient safety. PMID- 17850530 TI - Workforce perceptions of hospital safety culture: development and validation of the patient safety climate in healthcare organizations survey. AB - OBJECTIVE: To describe the development of an instrument for assessing workforce perceptions of hospital safety culture and to assess its reliability and validity. DATA SOURCES/STUDY SETTING: Primary data collected between March 2004 and May 2005. Personnel from 105 U.S. hospitals completed a 38-item paper and pencil survey. We received 21,496 completed questionnaires, representing a 51 percent response rate. STUDY DESIGN: Based on review of existing safety climate surveys, we developed a list of key topics pertinent to maintaining a culture of safety in high-reliability organizations. We developed a draft questionnaire to address these topics and pilot tested it in four preliminary studies of hospital personnel. We modified the questionnaire based on experience and respondent feedback, and distributed the revised version to 42,249 hospital workers. DATA COLLECTION: We randomly divided respondents into derivation and validation samples. We applied exploratory factor analysis to responses in the derivation sample. We used those results to create scales in the validation sample, which we subjected to multitrait analysis (MTA). PRINCIPAL FINDINGS: We identified nine constructs, three organizational factors, two unit factors, three individual factors, and one additional factor. Constructs demonstrated substantial convergent and discriminant validity in the MTA. Cronbach's alpha coefficients ranged from 0.50 to 0.89. CONCLUSIONS: It is possible to measure key salient features of hospital safety climate using a valid and reliable 38-item survey and appropriate hospital sample sizes. This instrument may be used in further studies to better understand the impact of safety climate on patient safety outcomes. PMID- 17850531 TI - Missing in action: care by physician assistants and nurse practitioners in national health surveys. AB - OBJECTIVE: To assess applicability of national health survey data for generalizable research on outpatient care by physician assistants (PAs) and nurse practitioners (NPs). DATA SOURCES: Methodology descriptions and 2003 data files from the National Ambulatory Medical Care Survey, the National Hospital Ambulatory Medical Care Survey, the Medical Expenditure Panel Survey, and the Community Tracking Study. STUDY DESIGN: Surveys were assessed for utility for research on PA and NP patient care, with respect to survey coverage, structure, content, generalizability to the U.S. population, and validity. National estimates of patient encounters, statistically adjusted for survey design and nonresponse, were compared across surveys. DATA COLLECTION/EXTRACTION METHODS: Surveys were identified through literature review, selected according to inclusion criteria, and analyzed based on methodology descriptions. Quantitative analyses used publicly available data downloaded from survey websites. PRINCIPAL FINDINGS: Surveys varied with respect to applicability to PA and NP care. Features limiting applicability included (1) sampling schemes that inconsistently capture nonphysician practice, (2) inaccurate identification of provider type, and (3) data structure that does not support analysis of team practice. CONCLUSIONS: Researchers using national health care surveys to analyze PA and NP patient interactions should account for design features that may differentially affect nonphysician data. Workforce research that includes NPs and PAs is needed for national planning efforts, and this research will require improved survey methodologies. PMID- 17850532 TI - Are the Current Population Survey uninsurance estimates too high? An examination of the imputation process. AB - RESEARCH OBJECTIVE: To determine whether the imputation procedure used to replace missing data by the U.S. Census Bureau produces bias in the estimates of health insurance coverage in the Current Population Survey's (CPS) Annual Social and Economic Supplement (ASEC). DATA SOURCE: 2004 CPS-ASEC. STUDY DESIGN: Eleven percent of the respondents to the monthly CPS do not take the ASEC supplement and the entire supplement for these respondents is imputed by the Census Bureau. We compare the health insurance coverage of these "full-supplement imputations" with those respondents answering the ASEC supplement. We then compare demographic characteristics of the two groups and model the likelihood of having insurance coverage given the data are imputed controlling for demographic characteristics. Finally, in order to gauge the impact of imputation on the uninsurance rate we remove the full-supplement imputations and reweight the data, and we also use the multivariate regression model to simulate what the uninsurance rate would be under the counter-factual simulation that no cases had the full-supplement imputation. POPULATION STUDIED: The noninstitutionalized U.S. population under 65 years of age in 2004. DATA EXTRACTION METHODS: The CPS-ASEC survey was extracted from the U.S. Census Bureau's FTP web page in September of 2004 (http://www.bls.census.gov/ferretftp.htm). PRINCIPAL FINDINGS: In the 2004 CPS ASEC, 59.3 percent of the full-supplement imputations under age 65 years had private health insurance coverage as compared with 69.1 percent of the nonfull supplement imputations. Furthermore, full-supplement imputations have a 26.4 percent uninsurance rate while all others have an uninsurance rate of 16.6 percent. Having imputed data remains a significant predictor of health insurance coverage in multivariate models with demographic controls. Both our reweighting strategy and our counterfactual modeling show that the uninsured rate is approximately one percentage point higher than it should be for people under 65 (i.e., approximately 2.5 million more people are counted as uninsured due to this imputation bias). CONCLUSIONS: The imputed ASEC data are coding too many people to be uninsured. The situation is complicated by the current survey items in the ASEC instrument allowing all members of a household to be assigned coverage with the single press of a button. The Census Bureau should consider altering its imputation specifications and, more importantly, altering how it collects survey data from those who respond to the supplement. IMPLICATIONS FOR POLICY DELIVERY OR PRACTICE: The bias affects many different policy simulations, policy evaluations and federal funding allocations that rely on the CPS-ASEC data. PRIMARY FUNDING SOURCE: The Robert Wood Johnson Foundation. PMID- 17850533 TI - Evaluation of three algorithms to identify incident breast cancer in Medicare claims data. AB - OBJECTIVE: To test the validity of three published algorithms designed to identify incident breast cancer cases using recent inpatient, outpatient, and physician insurance claims data. DATA: The Surveillance, Epidemiology, and End Results (SEER) registry data linked with Medicare physician, hospital, and outpatient claims data for breast cancer cases diagnosed from 1995 to 1998 and a 5 percent control sample of Medicare beneficiaries in SEER areas. STUDY DESIGN: We evaluate the sensitivity and specificity of three algorithms applied to new data compared with original reported results. Algorithms use health insurance diagnosis and procedure claims codes to classify breast cancer cases, with SEER as the reference standard. We compare algorithms by age, stage, race, and SEER region, and explore via logistic regression whether adding demographic variables improves algorithm performance. PRINCIPAL FINDINGS: The sensitivity of two of three algorithms is significantly lower when applied to newer data, compared with sensitivity calculated during algorithm development (59 and 77.4 percent versus 90 and 80.2 percent, p<.00001). Sensitivity decreases as age increases, and false negative rates are higher for cases with in situ, metastatic, and unknown stage disease compared with localized or regional breast cancer. Substantial variation also exists by SEER registry. There was potential for improvement in algorithm performance when adding age, region, and race to an indicator variable for whether the algorithm determined a subject to be a breast cancer case (p<.00001). CONCLUSIONS: Differential sensitivity of the algorithms by SEER region and age likely reflects variation in practice patterns, because the algorithms rely on administrative procedure codes. Depending on the algorithm, 3-5 percent of subjects overall are misclassified in 1998. Misclassification disproportionately affects older women and those diagnosed with in situ, metastatic, or unknown stage disease. Algorithms should be applied cautiously to insurance claims databases to assess health care utilization outside SEER-Medicare populations because of uneven misclassification of subgroups that may be understudied already. PMID- 17850534 TI - Quality by any other name?: a comparison of three profiling systems for assessing health care quality. AB - OBJECTIVE: Many performance measurement systems are designed to identify differences in the quality provided by health plans or facilities. However, we know little about whether different methods of performance measurement provide similar answers about the quality of care of health care organizations. To examine this question, we used three different measurement approaches to assess quality of care delivered in veteran affairs (VA) facilities. DATA SOURCES/STUDY SETTING: Medical records for 621 patients at 26 facilities in two VA regions. STUDY DESIGN: We examined agreements in quality conclusions using: focused explicit (38 measures for six conditions/prevention), global explicit (372 measures for 26 conditions/prevention), and structured implicit review physician rated care (a single global rating of care for three chronic conditions and overall acute, chronic and preventive care). Trained nurse abstractors and physicians reviewed all medical records. Correlations between scores from the three systems were adjusted for measurement error in each using multilevel regression models. RESULTS: Intercorrelations of scores were generally moderate to high across all three systems, and rose with adjustment for measurement error. Site-level correlations for prevention and diabetes care were particularly high. For example, adjusted for measurement error at the site level, prevention quality was correlated at 0.89 between the implicit and global systems, 0.67 between implicit and focused, and 0.73 between global and focused systems. CONCLUSIONS: We found moderate to high agreement in quality scores across the three profiling systems for most clinical areas, indicating that all three were measuring a similar construct called "quality." Adjusting for measurement error substantially enhanced our ability to identify this underlying construct. PMID- 17850537 TI - Neuroactive properties of reproductive steroids. AB - Migraine is 3 times more common in postpubertal women than in men. Migraine is frequently exacerbated perimenstrually and commonly occurs exclusively at that time. It is often benefited by pregnancy and menopause. Estrogen withdrawal has been implicated as a mechanism for triggering migraines. The mechanism, however, is not well understood. Reproductive steroids have neuroactive properties that can modulate neuronal morphology and physiology. Increasing evidence suggests that circulating reproductive steroid levels regulate the balance of neuroexcitatory and neuroinhibitory activities in some brain regions by influencing synaptic plasticity. Estrogen has neuroexcitatory, whereas progesterone has neuroinhibitory, effects in most preclinical and clinical models. Several neurotransmitter systems that are implicated in migraine vary with reproductive steroid levels during the reproductive cycle. Estrogen stabilization may provide effective treatment in susceptible women, especially for catamenially exacerbated migraine. PMID- 17850538 TI - Cortical spreading depression and estrogen. AB - Cortical spreading depression (CSD) is an electrophysiological phenomenon characterized by a wave of excitation followed by inhibition. The aura phase that precedes migraine headache in about 20-30% of migraineurs shares overlapping characteristics with CSD. Studies of rare autosomal-dominant forms of migraine with aura provide strong evidence that the threshold for evoking CSD and aura are related to neuronal excitability. Although the relationship between CSD and migraine without aura is not completely understood, the molecular abnormalities that predispose to migraine with aura illustrate the importance of physiologic events associated with neuronal hyperexcitability, and provide a basis for understanding a more generalized view of migraine. PMID- 17850539 TI - Understanding the causes and prevention of menstrual migraine: the role of estrogen. AB - Menstruation increases the risk of migraine in susceptible women. In a subpopulation of women with menstrual migraine, headaches occurring in association with onset of menses may be more severe and of longer duration than headaches experienced by the same woman at other times of her menstrual cycle. Although menstrual migraines share many clinical characteristics of other types of migraines, their occurrence is predictable provided that the patient has regular menstrual cycles. Therefore, short-term prevention regimens can be considered for women whose headaches are not adequately managed with acute therapies. PMID- 17850541 TI - Tracking the sudden oak death pathogen. AB - Invasive species are, by definition, unwelcome and pathogenic ones, especially so. Tracing the origins and spread of Phytophthora ramorum, the devastating 'Sudden Oak Death' pathogen, in the forests and nurseries of Oregon has revealed differences between forest and nursery pathogen populations that suggest discrete sources of primary inoculum initiate each type of outbreak. New information on the ecology and evolution of this pathogen is presented that helps gauge the effectiveness of quarantine and eradication programmes. PMID- 17850542 TI - Statistical analysis of amplified fragment length polymorphism data: a toolbox for molecular ecologists and evolutionists. AB - Recently, the amplified fragment length polymorphism (AFLP) technique has gained a lot of popularity, and is now frequently applied to a wide variety of organisms. Technical specificities of the AFLP procedure have been well documented over the years, but there is on the contrary little or scattered information about the statistical analysis of AFLPs. In this review, we describe the various methods available to handle AFLP data, focusing on four research topics at the population or individual level of analysis: (i) assessment of genetic diversity; (ii) identification of population structure; (iii) identification of hybrid individuals; and (iv) detection of markers associated with phenotypes. Two kinds of analysis methods can be distinguished, depending on whether they are based on the direct study of band presences or absences in AFLP profiles ('band-based' methods), or on allelic frequencies estimated at each locus from these profiles ('allele frequency-based' methods). We investigate the characteristics and limitations of these statistical tools; finally, we appeal for a wider adoption of methodologies borrowed from other research fields, like for example those especially designed to deal with binary data. PMID- 17850543 TI - Cross-species transfer of nuclear microsatellite markers: potential and limitations. AB - Molecular ecologists increasingly require 'universal' genetic markers that can easily be transferred between species. The distribution of cross-species transferability of nuclear microsatellite loci is highly uneven across taxa, being greater in animals and highly variable in flowering plants. The potential for successful cross-species transfer appears highest in species with long generation times, mixed or outcrossing breeding systems, and where genome size in the target species is small compared to the source. We discuss the implications of these findings and close with an outlook on potential alternative sources of cross-species transferable markers. PMID- 17850544 TI - Evolutionary trend of phylogenetic diversity of nitrogen fixation genes in the gut community of wood-feeding termites. AB - Nitrogen fixation by gut microorganisms is one of the crucial aspects of symbiosis in wood-feeding termites since these termites thrive on a nitrogen-poor diet. In order to understand the evolution of this symbiosis, we analysed the nitrogenase structural gene nifH in the gut microbial communities. In conjunction with the published sequences, we compared approximately 320 putatively functional NifH protein sequences obtained from a total of 19 termite samples that represent all the major branches of their currently proposed phylogeny, and from one species of the cockroach Cryptocercus that shares a common ancestor with termites. Using multivariate techniques for clustering and ordination, a phylogeny of NifH protein sequences was created and plotted variously with host termite families, genera, and species. Close concordance was observed between NifH communities and the host termites at genus level, but family level relationships were not always congruent with accepted termite clade structure. Host groups examined included basal families (Mastotermitidae, Termopsidae, Kalotermitidae, as well as Cryptocercus), the most derived lower termite family Rhinotermitidae, and subfamilies representing the advanced and highly diverse apical family Termitidae (Macrotermitinae, Termitinae, and Nasutitermitinae). This selection encompassed the major nesting and feeding styles recognized in termites, and it was evident that NifH phylogenetic divergence, as well as the occurrence of alternative nitrogenase-type NifH, was to some extent dependent on host lifestyle as well as phylogenetic position. PMID- 17850545 TI - Changes in composition of cuticular biochemicals of the facultatively polygynous ant Petalomyrmex phylax during range expansion in Cameroon with respect to social, spatial and genetic variation. AB - In social insects, biochemicals found at the surface of the cuticle are involved in the recognition process and in protection against desiccation and pathogens. However, the relative contribution of evolutionary forces in shaping diversity of these biochemicals remains largely unresolved in ants. We determined the composition of epicuticular biochemicals for workers sampled in 12 populations of the ant Petalomyrmex phylax from Cameroon. Genetic variation at 12 microsatellite markers was used to infer population history and to provide null expectations under the neutrality hypothesis. Genetic data suggest a recent southward range expansion of this ant species. Furthermore, there is a decline southward in the numbers of queens present in mature colonies. Here, we contrast the pattern of biochemical variation against genetic, social and spatial parameters. We thus provide the first estimates of the relative contribution of neutral and selective processes on variation of ant cuticular profile. Populations in migration-drift disequilibrium showed reduction of within-population variation for genetic markers as well as for cuticular profiles. In these populations, the cuticular profile became biased towards a limited number of high molecular weight molecules. Within- and among-population biochemical variation was explained by both genetic and social variation and by the spatial distribution of populations. We therefore propose that during range expansion of P. phylax, the composition of epicuticular compounds has been affected by a combination of neutral processes - genetic drift and spatially limited dispersal - and spatially varying selection, social organization and environmental effects. PMID- 17850546 TI - Molecular analysis of dispersal in giant pandas. AB - Although dispersal in the giant panda (Ailuropoda melanoleuca) is a demographic mechanism which can potentially counteract the negative effect of habitat fragmentation, little is known about dispersal in this species because of difficulties in observing individuals. Using data from faecal microsatellite genotyping, we compared the spatial distribution of giant pandas in two populations and the proximity of relatives in one key population to infer their dispersal pattern. We conclude that giant pandas exhibit female-biased dispersal because: (i) vAIc (variance of assignment index) for females was significantly larger than for males, suggesting that females comprise both 'local' and 'foreign' genotypes; (ii) the average spatial distance of related female dyads was significantly larger than that of males; (iii) larger r (relatedness), F(ST) (genetic variance among populations) and mAIc (mean of assignment index) values were found in males using the software FSTAT, although the differences were not significant; (iv) males set up territories neighbouring to their birth place; (v) significant population structure using microsatellites with a concomitant lack of mitochondrial structure was found in a previous study, possibly indicating more extensive female dispersal; and (vi) female-biased dispersal was strongly supported by evidence from concomitant ecological studies. Considering previous ecological data and life-history characteristics of the giant panda, female biased dispersal is most likely to be due to competition for birth dens among females, inbreeding avoidance and enhancing inclusive fitness among related males. PMID- 17850547 TI - Long distance pollen-mediated gene flow at a landscape level: the weed beet as a case study. AB - Gene flow is a crucial parameter that can affect the organization of genetic diversity in plant species. It has important implications in terms of conservation of genetic resources and of gene exchanges between crop to wild relatives and within crop species complex. In the Beta vulgaris complex, hybridization between crop and wild beets in seed production areas is well documented and the role of the ensuing hybrids, weed beets, as bridges towards wild forms in sugar beet production areas have been shown. Indeed, in contrast to cultivated beets that are bi-annual, weed beets can bolt, flower and reproduce in the same crop season. Nonetheless, the extent of pollen gene dispersal through weedy lineages remains unknown. In this study, the focus is directed towards weed to-weed gene flow, and we report the results of a pollen-dispersal analysis within an agricultural landscape composed of five sugar beet fields with different levels of infestation by weed beets. Our results, based on paternity analysis of 3240 progenies from 135 maternal plants using 10 microsatellite loci, clearly demonstrate that even if weedy plants are mostly pollinated by individuals from the same field, some mating events occur between weed beets situated several kilometres apart (up to 9.6 km), with rates of interfield detected paternities ranging from 11.3% to 17.5%. Moreover, we show that pollen flow appears to be more restricted when individuals are aggregated as most mating events occurred only for short-distance classes. The best-fit dispersal curves were fat-tailed geometric functions for populations exhibiting low densities of weed beets and thin-tailed Weibull function for fields with weed beet high densities. Thus, weed beet populations characterized by low density with geographically isolated individuals may be difficult to detect but are likely to act as pollen traps for pollen emitted by close and remote fields. Hence, it appears evident that interfield pollen-mediated gene flow between weed beets is almost unavoidable and could contribute to the diffusion of (trans)genes in the agricultural landscape. PMID- 17850548 TI - Historical and biological determinants of genetic diversity in the highly endemic triploid sea lavender Limonium dufourii (Plumbaginaceae). AB - Microsatellite markers were used to evaluate the genetic diversity and population genetic structure in the critically endangered Limonium dufourii (Plumbaginaceae), a highly endemic triploid species from the coasts of eastern Spain. Sixty-five alleles from 13 microsatellite regions were amplified in a sample of 122 individuals collected from the six extant populations. Microsatellite patterns were consistent with the triploid nature of L. dufourii. Alleles were unambiguously assigned to two different parental subgenomes in this hybrid species and the greater contribution of the diploid parental subgenome was confirmed. Eleven, 25 and 26 multilocus genotypes were recorded from the haploid, diploid and from the combined information of both subgenomes, respectively. Genetic diversity was mostly distributed among populations (72.06% of the total genetic variation). Genotypes from Marjal del Moro populations grouped into two highly structured clusters (88.41% of the total variance). The observed patterns of distribution of genetic diversity are interpreted to result from multiple hybridization events and isolation between populations. Threats to this species are mainly anthropogenic (urbanization and tourism pressure), although stochastic risks cannot be ignored. Therefore, in order to preserve extant genetic variation of L. dufourii, in situ strategies such as the preservation of its habitat are a high priority. Several recommendations in order to assist ex situ measures to guarantee the success of conservation strategies and maintain the relationships between individuals and populations are proposed. PMID- 17850549 TI - Population structure of a large blue butterfly and its specialist parasitoid in a fragmented landscape. AB - Habitat fragmentation may interrupt trophic interactions if herbivores and their specific parasitoids respond differently to decreasing connectivity of populations. Theoretical models predict that species at higher trophic levels are more negatively affected by isolation than lower trophic level species. By combining ecological data with genetic information from microsatellite markers we tested this hypothesis on the butterfly Maculinea nausithous and its specialist hymenopteran parasitoid Neotypus melanocephalus. We assessed the susceptibility of both species to habitat fragmentation by measuring population density, rate of parasitism, overall genetic differentiation (theta(ST)) and allelic richness in a large metapopulation. We also simulated the dynamics of genetic differentiation among local populations to asses the relative effects of migration rate, population size, and haplodiploid (parasitoid) and diploid (host) inheritance on metapopulation persistence. We show that parasitism by N. melanocephalus is less frequent at larger distances to the nearest neighbouring population of M. nausithous hosts, but that host density itself is not affected by isolation. Allelic richness was independent of isolation, but the mean genetic differentiation among local parasitoid populations increased with the distance between these populations. Overall, genetic differentiation in the parasitoid wasp was much greater than in the butterfly host and our simulations indicate that this difference is due to a combination of haplodiploidy and small local population sizes. Our results thus support the hypothesis that Neotypus parasitoid wasps are more sensitive to habitat fragmentation than their Maculinea butterfly hosts. PMID- 17850550 TI - The genetic structure of cattle populations (Bos taurus) in northern Eurasia and the neighbouring Near Eastern regions: implications for breeding strategies and conservation. AB - We investigated the genetic structure and variation of 21 populations of cattle (Bos taurus) in northern Eurasia and the neighbouring Near Eastern regions of the Balkan, the Caucasus and Ukraine employing 30 microsatellite markers. By analyses of population relationships, as well as by a Bayesian-based clustering approach, we identified a genetic distinctness between populations of modern commercial origin and those of native origin. Our data suggested that northern European Russia represents the most heavily colonized area by modern commercial cattle. Further genetic mixture analyses based on individual assignment tests found that native Red Steppe cattle were also employed in the historical breeding practices in Eastern Europe, most probably for incorporating their strong and extensive adaptability. In analysis of molecular variance, within-population differences accounted for approximately 90% of the genetic variation. Despite some correspondence between geographical proximity and genetic similarity, genetic differentiation was observed to be significantly associated with the difference in breeding purpose among the European populations (percentage of variance among groups and significance: 2.99%, P = 0.02). Our findings give unique genetic insight into the historical patterns of cattle breeding practices in the former Soviet Union. The results identify the neighbouring Near Eastern regions such as the Balkan, the Caucasus and Ukraine, and the isolated Far Eastern Siberia as areas of 'genetic endemism', where cattle populations should be given conservation priority. The results will also be of importance for cost-effective management of their future utilization. PMID- 17850551 TI - Comparative estimation of effective population sizes and temporal gene flow in two contrasting population systems. AB - Estimation of effective population sizes (N(e)) and temporal gene flow (N(e)m, m) has many implications for understanding population structure in evolutionary and conservation biology. However, comparative studies that gauge the relative performance of N(e), N(e)m or m methods are few. Using temporal genetic data from two salmonid fish population systems with disparate population structure, we (i) evaluated the congruence in estimates and precision of long- and short-term N(e), N(e)m and m from six methods; (ii) explored the effects of metapopulation structure on N(e) estimation in one system with spatiotemporally linked subpopulations, using three approaches; and (iii) determined to what degree interpopulation gene flow was asymmetric over time. We found that long-term N(e) estimates exceeded short-term N(e) within populations by 2-10 times; the two were correlated in the system with temporally stable structure (Atlantic salmon, Salmo salar) but not in the highly dynamic system (brown trout, Salmo trutta). Four temporal methods yielded short-term N(e) estimates within populations that were strongly correlated, and these were higher but more variable within salmon populations than within trout populations. In trout populations, however, these short-term N(e) estimates were always lower when assuming gene flow than when assuming no gene flow. Linkage disequilibrium data generally yielded short-term N(e) estimates of the same magnitude as temporal methods in both systems, but the two were uncorrelated. Correlations between long- and short-term geneflow estimates were inconsistent between methods, and their relative size varied up to eightfold within systems. While asymmetries in gene flow were common in both systems (58-63% of population-pair comparisons), they were only temporally stable in direction within certain salmon population pairs, suggesting that gene flow between particular populations is often intermittent and/or variable. Exploratory metapopulation N(e) analyses in trout demonstrated both the importance of spatial scale in estimating N(e) and the role of gene flow in maintaining genetic variability within subpopulations. Collectively, our results illustrate the utility of comparatively applying N(e), N(e)m and m to (i) tease apart processes implicated in population structure, (ii) assess the degree of continuity in patterns of connectivity between population pairs and (iii) gauge the relative performance of different approaches, such as the influence of population subdivision and gene flow on N(e) estimation. They further reiterate the importance of temporal sampling replication in population genetics, the value of interpreting N(e)or m in light of species biology, and the need to address long standing assumptions of current N(e), N(e)m or m models more explicitly in future research. PMID- 17850552 TI - Traces of ancient range shifts in a mountain plant group (Androsace halleri complex, Primulaceae). AB - Phylogeographical studies frequently detect range shifts, both expansions (including long-distance dispersal) and contractions (including vicariance), in the studied taxa. These processes are usually inferred from the patterns and distribution of genetic variation, with the potential pitfall that different historical processes may result in similar genetic patterns. Using a combination of DNA sequence data from the plastid genome, AFLP fingerprinting, and rigorous phylogenetic and coalescence-based hypothesis testing, we show that Androsace halleri (currently distributed disjunctly in the northwestern Iberian Cordillera Cantabrica, the eastern Pyrenees, and the French Massif Central and Vosges), or its ancestor, was once more widely distributed in the Pyrenees. While there, it hybridized with Androsace laggeri and Androsace pyrenaica, both of which are currently allopatric with A. halleri. The common ancestor of A. halleri and the north Iberian local endemic Androsace rioxana probably existed in the north Iberian mountain ranges with subsequent range expansion (to the French mountain ranges of the Massif Central and the Vosges) and allopatric speciation (A. rioxana, A. halleri in the eastern Pyrenees, A. halleri elsewhere). We have thus been able to use the reticulate evolution in this species group to help elucidate its phylogeographical history, including evidence of range contraction. PMID- 17850553 TI - Nuclear vs. plastid data: complex Pleistocene history of a circumpolar key species. AB - To fully understand the contemporary genetic structure of plants, both nuclear and plastid markers are needed. Three chloroplast DNA (cpDNA) lineages, which probably diverged before the major Pleistocene glaciations, have been identified in the circumpolar/circumboreal Vaccinium uliginosum. Here we investigate its nuclear DNA variation using nuclear ribosomal internal transcribed spacer (ITS) sequences, DNA ploidy level measurements and amplified fragment length polymorphisms (AFLPs). We also extend the cpDNA dataset. Two ITS lineages, corresponding to diploids and tetraploids, respectively, were identified. However, both main sequence types apparently occurred in most individual plants but showed ploidy-biased homogenization and possibly reflect paralogy predating the origin of V. uliginosum. The ploidy levels were largely consistent with the cpDNA lineages, suggesting that the initial cpDNA divergence followed early polyploidizations. Five main AFLP groups were identified, consistent with recent glacial refugia in Beringia, western Siberia, the southern European mountains and areas south/east of the Scandinavian and Laurentide ice sheets. Except from the southern European mountains, there has been extensive expansion from all refugia, resulting in several contact zones. Surprisingly, the presumably older ploidy and cpDNA patterns were partly inconsistent with the main AFLP groups and more consistent with AFLP subgroups. A likely major driver causing the inconsistencies is recent nuclear gene flow via unreduced pollen from diploids to tetraploids. This may prevent cytoplasmic introgression and result in overlayed patterns formed by processes dominating at different time scales. The data also suggest more recent polyploidizations, as well as several chloroplast capture events, further complicating this scenario. This study highlights the importance of combining different marker systems to unravel intraspecific histories. PMID- 17850554 TI - Interspecific phylogenetic analysis enhances intraspecific phylogeographical inference: a case study in Pinus lambertiana. AB - Pinus lambertiana (sugar pine) is an economically and ecologically important conifer with a 1600-km latitudinal range extending from Oregon, USA, to northern Baja California, Mexico. Like all North American white pines (subsect. Strobus), sugar pine is highly susceptible to white pine blister rust, a disease caused by the fungus Cronartium ribicola. We conducted a chloroplast DNA (cpDNA) survey of Pinus subsect. Strobus with comprehensive geographical sampling of P. lambertiana. Sequence analysis of 12 sugar pine individuals revealed strong geographical differentiation for two chloroplast haplotypes. A diagnostic restriction site survey of an additional 72 individuals demarcated a narrow 150 km contact zone in northeastern California. In the contact zone, maternal (megagametophtye) and paternal (embryo) haplotypes were identified in 31 single seeds, demonstrating bidirectional pollen flow extending beyond the range of maternal haplotypes. The frequencies of the Cr1 allele for white pine blister rust major gene resistance, previously determined for 41 seed zones, differ significantly among seed zones that are fixed for the alternate haplotypes, or contain a mixture of both haplotypes. Interspecific phylogenetic analysis reveals that the northern sugar pine haplotype belongs to a clade that includes Pinus albicaulis (whitebark pine) and all of the East Asian white pines. Furthermore, there is little cpDNA divergence between northern sugar pine and whitebark pine (dS = 0.00058). These results are consistent with a Pleistocene migration of whitebark pine into North America and subsequent chloroplast introgression from whitebark pine to sugar pine. This study demonstrates the importance of placing phylogeographical results in a broader phylogenetic context. PMID- 17850555 TI - Multiple paternity and kin recognition mechanisms in a guppy population. AB - Help directed toward kin (nepotism) is an important example of social behaviour. Such helping behaviour requires a mechanism to distinguish kin from nonkin. The prevailing kin recognition hypothesis is that when familiarity is a reliable cue of relatedness, other mechanisms of recognition will not evolve. However, when familiarity is an unreliable cue of relatedness, kin recognition by phenotype matching is instead predicted to evolve. Here we use genetic markers to show that guppies (Poecilia reticulata) from a population in a tributary of the Paria River in Trinidad are characterized by a high degree of multiple mating with 95% of broods having more than one sire and some dams having offspring sired by six males. These levels of multiple mating are the highest reported among live bearing fishes. The mean relatedness of brood-mates was 0.36 (as compared to 0.5 for full-siblings). Therefore, familiarity does not seem to be a reliable mechanism to assess full-sibling relatedness. Using two-choice behavioural trials, we found that juveniles from this population use both phenotype matching and familiarity to distinguish kin from nonkin. However, we did not find strong evidence that the guppies use these mechanisms to form shoals of related individuals as adults, which is similar to results from other guppy populations in Trinidad. The use of both familiarity and phenotype matching is discussed in the context of the Paria River guppy population's mating system and ecology. Overall, these data provide support for the kin recognition hypothesis and increase our understanding of the evolution of kin recognition systems. PMID- 17850556 TI - A spatial analysis method (SAM) to detect candidate loci for selection: towards a landscape genomics approach to adaptation. AB - The detection of adaptive loci in the genome is essential as it gives the possibility of understanding what proportion of a genome or which genes are being shaped by natural selection. Several statistical methods have been developed which make use of molecular data to reveal genomic regions under selection. In this paper, we propose an approach to address this issue from the environmental angle, in order to complement results obtained by population genetics. We introduce a new method to detect signatures of natural selection based on the application of spatial analysis, with the contribution of geographical information systems (GIS), environmental variables and molecular data. Multiple univariate logistic regressions were carried out to test for association between allelic frequencies at marker loci and environmental variables. This spatial analysis method (SAM) is similar to current population genomics approaches since it is designed to scan hundreds of markers to assess a putative association with hundreds of environmental variables. Here, by application to studies of pine weevils and breeds of sheep we demonstrate a strong correspondence between SAM results and those obtained using population genetics approaches. Statistical signals were found that associate loci with environmental parameters, and these loci behave atypically in comparison with the theoretical distribution for neutral loci. The contribution of this new tool is not only to permit the identification of loci under selection but also to establish hypotheses about ecological factors that could exert the selection pressure responsible. In the future, such an approach may accelerate the process of hunting for functional genes at the population level. PMID- 17850557 TI - Glucocorticoids for peri-operative analgesia: how far are we from general recommendations? PMID- 17850558 TI - Torsten Gordh celebrates his 100th anniversary. PMID- 17850559 TI - The effect of propofol on actin, ERK-1/2 and GABAA receptor content in neurones. AB - AIM: Interaction with the gamma-aminobutyric acid receptor (GABA(A)R) complex is recognized as an important component of the mechanism of many anaesthetic agents, including propofol. The aims of this study were to investigate the effect of propofol on GABA(A)R, to determine whether exposure of neurones to propofol influences the localization of GABA(A)R within the cell and to look for cytoskeletal changes that may be connected with activation, such as the mitogen activated protein kinase (MAPK) pathway. METHODS: Primary cortical cell cultures from rat, with and without pre-incubation with the GABA(A)R antagonist bicuculline, were exposed to propofol. The cells were lysed and separated into membrane and cytosolic fractions. Immunoblot analyses of filamentous actin (F actin), the GABA(A)beta(2)-subunit receptor and extracellular signal-regulated kinase-1/2 (ERK-1/2) were performed. RESULTS: Propofol triggers an increase in GABA(A)R, actin content and ERK-1/2 phosphorylation in the cytosolic fraction. In the membrane fraction, there is a decrease in GABA(A)beta(2)-subunit content and an increase in both actin content and ERK-1/2 phosphorylation. The GABA(A)R antagonist bicuculline blocks the propofol-induced changes in F-actin, ERK and GABA(A)beta(2)-subunit content, and ERK-1/2 phosphorylation. CONCLUSION: We believe that propofol triggers a dose-dependent internalization of the GABA(A)beta(2)-subunit. The increase in internal GABA(A)beta(2)-subunit content exhibits a close relationship to actin polymerization and to an increase in ERK 1/2 activation. Actin contributes to the internalization sequestering of the GABA(A)beta(2)-subunit. PMID- 17850560 TI - Oxygenation and release of inflammatory mediators after off-pump compared with after on-pump coronary artery bypass surgery. AB - BACKGROUND: In a previous study, we showed that oxygenation was impaired for up to 5 day after conventional coronary artery bypass grafting (CABG). As cardiopulmonary bypass (CPB) may have a detrimental effect on pulmonary function, we hypothesized that coronary revascularization grafting without the use of CPB (OPCAB) would affect post-operative oxygenation and release of inflammatory mediators less compared with CABG. METHODS: Low-risk patients scheduled for elective coronary revascularization were randomly assigned to one of two groups (CABG, n = 17 or OPCAB, n = 18). Two parameters of oxygenation, shunt (%) and ventilation-perfusions mismatch, described as DeltaPO(2) (kPa), were estimated for up to 5 days post-operatively. Systemic release of interleukin (IL)-6, -8 and -10, C-reactive protein (CRP) and neutrophils were measured in peripheral blood samples for up to 3 days post-operatively. The lungs participation in the cytokine response was evaluated from mixed venous blood samples taken within the first 16 h post-operatively. RESULTS: OPCAB was followed by a higher shunt (P = 0.047), with no difference (P = 0.47) in the deterioration of DeltaPO(2) between the groups. OPCAB was followed by an attenuated systemic release of IL-8 (P = 0.041) and IL-10 (P = 0.006), while the release of IL-6 (P = 0.94), CRP (P = 0.121) and neutrophils (P = 0.078) did not differ between the groups. Indications of an uptake of cytokines in the lungs were found after OPCAB. CONCLUSIONS: When comparing OPCAB with CABG, oxygenation was more affected and only part of the systemic inflammatory response was attenuated. PMID- 17850561 TI - Induced mild hypothermia reduces mortality during acute inflammation in rats. AB - BACKGROUND: Hypothermia has been proposed as a therapeutic possibility in brain trauma, cardiac arrest and hemorrhagic shock. Experimental studies have shown that hypothermia may act by modulating the inflammatory response during endotoxemia. This study was carried out to test whether hypothermia could protect rats from endotoxemic insult. METHODS: After general anesthesia and oro-tracheal intubation, Sprague-Dawley rats were randomly assigned to either a hypothermic group or normothermic group. In each group, rats received intraperitoneal lipopolysaccharide (LPS) (10 or 20 mg/kg). Blood samples were taken prior to and 2 h after LPS injection to measure blood gases, liver enzymes, muscular enzymes, tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) plasma levels. After 2 h of hypothermia, the rats were extubated and brought back to their cages. The mortality rate was observed for 7 days following endotoxemia. In a second set of experiments, hypothermia was induced 1 h after endotoxemia (10 mg/kg of intraperitoneal LPS) and the mortality rate was observed for the following 7 days. RESULTS: The survival rate was significantly increased in the hypothermic group relative to the normothermic group, regardless of LPS dose. This increased survival rate was also observed when hypothermia was induced 1 h after endotoxemia. In the hypothermic group, IL-10 and the DeltaIL-10/DeltaTNF alpha ratio were significantly increased relative to those in the normothermic group. CONCLUSION: Induced mild hypothermia reduces mortality during endotoxemia in rats. The modulation of the inflammatory response, with an increase in anti inflammatory cytokines, may be involved in this protective effect. PMID- 17850562 TI - Effect of levosimendan on ventriculo-arterial coupling in patients with ischemic cardiomyopathy. AB - BACKGROUND: Levosimendan, a novel calcium sensitizer, enhances myocardial contractility without affecting intracellular calcium concentration. It also dilates peripheral arterial vessels by acting on ATP-dependent K(+) channels. Ventriculo-arterial coupling, the relationship between myocardial contractility and the arterial system, describes the efficiency of the cardiovascular system by analysing the relationship between myocardial contractility expressed by ventricular elastance (E(es)) and arterial elastance (E(a)). The aim of this prospective clinical investigation was to evaluate the effects of levosimendan on ventriculo-arterial coupling in patients with ischemic cardiomyopathy. METHODS: Fifteen patients with stable angina and left ventricular dysfunction underwent elective coronary surgery. Before surgery started, ventriculo-arterial coupling and several variables of cardiovascular performance were assessed by invasive monitoring and transoesophageal echocardiography before and after administration of levosimendan (12 mug/kg bolus) in coronary patients under general anesthesia. RESULTS: The cardiac index and ejection fraction increased significantly [from 1.92 +/- 0.4 to 2.1 +/- 0.4 l/min/m(2) (P = 0.0004) and from 31% +/- 6 to 40% +/- 9 (P = 0.001), respectively], while mean arterial pressure and systemic vascular resistances decreased significantly [from 83 +/- 10 to 72 +/- 5 mmHg (P = 0.0016) and from 997 +/- 341 to 855 +/- 324 dyne s/cm(5) (P = 0.0002), respectively]. After administration of levosimendan, E(a) decreased significantly (from 4.3 +/- 1.8 to 3.2 +/- 1.3 mmHg/ml/m(2), P= 0.005), while E(es) significantly increased (from 2.8 +/- 1.6 to 4.4 +/- 2.3 mmHg/ml/m(2), P= 0.05); as a result, E(a)/E(es) decreased significantly (from 1.76 +/- 1 to 0.83 +/- 0.2, P= 0.002). CONCLUSION: Levosimendan improves ventriculo-arterial coupling and cardiovascular performance in coronary patients with left ventricular dysfunction by enhancing myocardial contractility and reducing arterial elastance. PMID- 17850563 TI - Mortality after discharge from the intensive care unit during the early weekend period: a population-based cohort study in Denmark. AB - BACKGROUND: As a result of a shortage of intensive care capacity, patients may be discharged prematurely early during weekends which may lead to an increased mortality and risk of readmission to intensive care units (ICU). We examined whether discharge from the ICU during the first part of the weekend was associated with an increased mortality and readmission to the ICU. METHODS: The study was conducted at a university clinic of internal medicine and included all patients admitted for the first time to the ICU, and discharged alive in the period 1 January 2001 to 31 December 2005. Patients were divided in those discharged between 00.00 h Friday and 24.00 h Saturday (weekend group) and those discharged Sunday to Thursday (non-weekend group). The main outcome was time from discharge from the ICU to the combined endpoint death or re-admission to ICU which ever came first. We used Kaplan-Meier analysis and Cox's proportional hazards regression to compute survival curves and risk ratio estimates. RESULTS: There were 228 patients in the weekend group and 555 patients in the non-weekend group. Crude and adjusted 28-day risk ratio of the combined endpoint was 1.50 [95% confidence interval (CI): 1.15-1.97] and 1.43 (1.09-1.87) in the weekend group. Although an increased risk of death was observed in the weekend group immediately after discharge from the ICU, the difference in mortality between the two groups had disappeared after 2 years. CONCLUSION: Medical patients discharged from the ICU early in the weekends seem to have an increased mortality and risk of readmission to the ICU. PMID- 17850564 TI - Tracheostomy: current practice on timing, correction of coagulation disorders and peri-operative management - a postal survey in the Netherlands. AB - BACKGROUND: Several factors may delay tracheostomy. As many critically ill patients either suffer from coagulation abnormalities or are being treated with anticoagulants, fear of bleeding complications during the procedure may also delay tracheostomy. It is unknown whether such (usually mild) coagulation abnormalities are corrected first and to what extent. The purpose of this study was to ascertain current practice of tracheostomy in the Netherlands with regard to timing, pre-operative correction of coagulation disorders and peri-/intra operative measures. METHODS: In October 2005, a questionnaire was sent to the medical directors of all non-pediatric ICUs with >/=5 beds suitable for mechanical ventilation in the Netherlands. RESULTS: A response was obtained from 44 (64%) out of 69 ICUs included in the survey. Seventy-five percent of patients receive tracheostomy within 2 days after the decision to proceed with a tracheostomy. Reasons indicated as frequent causes for delay were most often logistical factors. A heterogeneous attitude exists regarding values of coagulation parameters acceptable to perform tracheostomy. Fifty percent of the respondents have no guideline on correction of coagulation disorders or anticoagulant therapy before tracheostomy. Antimicrobial prophylaxis is almost never administered before tracheostomy. Forty-eight percent mentioned always using endoscopic guidance and 66% of ICUs only perform chest radiography on indication. CONCLUSIONS: There is a high variation in peri- and intra-operative practice of tracheostomy in the Netherlands. Especially on the subject of coagulation and tracheostomy there are different opinions and protocols are often lacking. PMID- 17850565 TI - The effects of vasoactive agents, platelet agonists and anticoagulation on thrombelastography. AB - BACKGROUND: Platelet activation is a critical step in primary hemostasis and clot formation. We tested a hypothesis that platelet stimulating effects of vasoactive agents or platelet agonists could be shown using thrombelastography (TEG) as faster onset or increased clot strength. We further examined if TEG could be modified to evaluate activated platelets as a reversal of anticoagulation in the presence of partial thrombin inhibition. METHODS: Blood samples were obtained from 126 non-cardiac surgical patients. Effects of vasoactive agents on TEG and aggregometry were examined using epinephrine, norepinephrine, vasopressin, desmopressin acetate, milrinone and olprinone (Experiment I). Platelet agonists (epinephrine, ADP and collagen) were separately tested on TEG (Experiment II). Effects of platelet agonists (ADP and collagen) on TEG under anticoagulation in the absence or presence of abciximab were studied (Experiment III). We also tested antiplatelet effects of milrinone and olprinone in the presence of anticoagulants on TEG (Experiment IV). RESULTS: Neither vasoactive agents nor platelet agonists affected TEG or aggregometry results except for milrinone and olprinone on aggregometry (Experiment I, II). Platelet agonists facilitated clotting in the presence of anticoagulants (Experiment III). Abciximab-treated platelets still exhibited procoagulant effects in the presence of heparin, while not in the presence of argatroban (Experiment III). Platelet inhibition on the modified TEG was more extensive with milrinone than olprinone, and it was dose dependent (Experiment IV). CONCLUSION: Modified TEG using heparin or argatroban might delineate the procoagulant effects of platelets by adding platelet specific agonist. PMID- 17850566 TI - Detection of tracheal malpositioning of nasogastric tubes using endotracheal cuff pressure measurement. AB - BACKGROUND: Insertion of a gastric tube (GT) in anaesthetized, paralyzed and intubated patients may be difficult. Tracheobronchial malposition of a GT may result in deleterious consequences. The purpose of this study was to determine the reliability of tracheal cuff pressure measurement to detect endobronchial malposition of GTs. We compared this new method with the measurement of exhaled CO(2) through the GT. METHODS: Thirty patients under general anesthesia and orotracheal intubation were analysed. First, the cuff pressure of the low-volume endotracheal tube (ET; ID 7.0-8.5 mm) was increased to 40 cmH(2)O. Then, in a randomized fashion, the GT (18 Charriere) was inserted consecutively into the trachea and oesophagus or vice versa. Cuff pressure was monitored continuously while advancing the GT. Furthermore, a capnograph was connected to the gastric tube and the aspirated PCO(2) was monitored. RESULTS: Advancement of the gastric tube into the oesophagus increased ET cuff pressure by 1 +/- 1 cmH(2)O, while endotracheal placement of the GT increased cuff pressure by 28 +/- 8 cmH(2)O (P < 0.001). Using an increase of >10 cmH(2)O in cuff pressure detected endotracheal malpositioning of the GT with 100% sensitivity and specificity. In 28 out of 30 cases, PCO(2) increased by more than 2.6 kPa. Thus, the PCO(2) approach failed to detect tracheal malpositioning in two cases resulting in a sensitivity of 93.3%. CONCLUSIONS: In intubated patients, cuff pressure measurement during insertion of a gastric tube is a new, simple and reliable bedside method to detect endotracheal malpositioning of a GT. PMID- 17850567 TI - Post-operative recovery after laparoscopic cholecystectomy. PMID- 17850569 TI - Endogenous glucose production during surgery and anaesthesia. PMID- 17850571 TI - Bronchoscopic removal of mucus casts in a boy with plastic bronchitis. PMID- 17850572 TI - Ketamine sedation to perform caudal anaesthesia in children in remote locations. PMID- 17850573 TI - The development of probiotics for the control of multiple bacterial diseases of rainbow trout, Oncorhynchus mykiss (Walbaum). AB - JB-1 and GC2, which were equated with Bacillus sp. and Aeromonas sobria respectively, were recovered from the digestive tract of rainbow trout, Oncorhynchus mykiss and ghost carp, Cyprinus sp. respectively, and demonstrated effectiveness as probiotics for the control of infections caused by Aeromonas salmonicida, Lactococcus garvieae, Streptococcus iniae, Vibrio anguillarum, Vibrio ordalii and Yersinia ruckeri. When administered to rainbow trout (average weight = 12 g) for 14 days in feed dosed at 2 x 10(8) cells g(-1) of feed, JB-1 led to a reduction in mortalities to 0-13% after challenge with a range of bacterial pathogens compared to 80-100% mortalities of the controls. Similarly, use of GC2 reduced mortalities to 0-16% following the challenge compared to 80 100% mortalities of the controls. The mode of action reflected nutrition, production of inhibitory substances and stimulation of the innate immune responses. Specifically, JB-1 and especially GC2 were positive for siderophore and chitinase production, and increased lysozyme, phagocytic and respiratory burst activity. PMID- 17850574 TI - Susceptibility of channel catfish, Ictalurus punctatus (Rafinesque), to Edwardsiella ictaluri challenge following copper sulphate exposure. AB - Channel catfish, Ictalurus punctatus (Rafinesque), with or without a preliminary 24 h exposure to 2 mg copper sulphate L(-1), were challenged with 7.5 x 10(6) colony forming units L(-1) of Edwardsiella ictaluri to determine the effect of copper sulphate on disease resistance. Catfish previously exposed to copper sulphate were significantly more resistant to the bacterial challenge than those not exposed. Catfish not exposed to copper sulphate suffered 35.5% mortality while catfish exposed to copper sulphate experienced 14.1% mortality. Copper concentrations were the same in tank waters of both exposed and control fish at the time of challenge, eliminating the possibility that copper in the water may have been toxic to bacteria. Copper concentrations in freeze dried and ground tissues of unexposed, exposed, and purged channel catfish were highest in fish before copper sulphate exposures suggesting that elevated tissue levels of copper were not responsible for the increased resistance to bacterial challenge. Competition for sites of bacterial attachment to gill or epithelial cells may account for the reduction in mortality; although this is not supported by the low copper content of fish tissue after copper exposure. PMID- 17850575 TI - Experimental exposure of zebrafish, Danio rerio (Hamilton), to Mycobacterium marinum and Mycobacterium peregrinum reveals the gastrointestinal tract as the primary route of infection: a potential model for environmental mycobacterial infection. AB - The natural route by which fish become infected with mycobacteria is unknown. Danio rerio (Hamilton) were exposed by bath immersion and intubation to Mycobacterium marinum and Mycobacterium peregrinum isolates obtained from diseased zebrafish. Exposed fish were collected over the course of 8 weeks and examined for the presence of mycobacteriosis. Mycobacteria were consistently cultured from the intestines, and often from the livers and spleens of fish exposed by both methods. Mycobacteria were not observed in the gills. Histological analysis revealed that fish infected with M. marinum often developed granulomas accompanied by clinical signs of mycobacteriosis, while infection with M. peregrinum infrequently led to clinical signs of disease. Passage of the bacteria through environmental amoebae (Acanthamoeba castellani) was associated with increased growth of M. peregrinum over the course of 8 weeks, when compared to infection with the bacteria not passed through amoebae. The results provide evidence that zebrafish acquire mycobacteria primarily through the intestinal tract, resulting in mycobacterial dissemination. PMID- 17850576 TI - Increased systemic vascular resistance in Atlantic salmon, Salmo salar L., affected with amoebic gill disease. AB - Previous investigations into the pathophysiology of amoebic gill disease (AGD) have suggested that there are probable cardiovascular effects associated with this disease. In the present study Atlantic salmon, Salmo salar L., were experimentally infected by cohabitation with diseased individuals. Two commonly used vasodilators, sodium nitroprusside (SNP) and captopril, the angiotensin converting enzyme (ACE) inhibitor, were used as tools to investigate possible vasoconstriction and/or renin-angiotensin system (RAS) dysfunction in AGD affected animals. Within the SNP trial, results showed that AGD-affected fish exhibited lowered cardiac output (Q), lowered cardiac stroke volume (V(S)) and a significantly elevated systemic vascular resistance (R(S)) compared with non affected naive counterparts. These effects were totally abolished following SNP administration (40 microg kg(-1)), however significant cardiovascular effects associated with SNP were not observed. Within the captopril trial, where AGD affected fish were more diseased compared with the SNP trial, a significant hypertension was observed in AGD-affected fish. Captopril administration (10(-4) mol L(-1) at 1 mL kg(-1)) resulted in a significant drop in dorsal aortic pressure (P(DA)) for both AGD-affected and naive control fish. In terms of peak individual responses, captopril administration effectively lowered P(DA) in both AGD-affected and naive control groups equally. The drop in P(DA) following SNP administration however was significantly greater in AGD-affected fish potentially suggesting disease-related vasoconstriction. The lack of significant cardiovascular effects directly associated with both SNP and captopril administrations possibly relate to the 6 h recovery period following surgical procedures. However, while variable, these results do suggest that there are significant cardiovascular effects including vasoconstriction and hypertension associated with AGD. PMID- 17850577 TI - Suspected myocardial necrosis in farmed Atlantic salmon, Salmo salar L.: a field case. AB - Arteriosclerosis of the coronary artery has been described as a 'fact of life' for Pacific and Atlantic salmonids due to the high prevalence in spawning fish. The lesions are believed to be the result of overstretching of the highly distensible bulbus arteriosus whereby the endothelium of the main coronary vessel becomes mechanically damaged and a smooth muscle proliferation ensues with resultant partial occlusion of the vessel. The physiological significance for the function of the heart has yet to be demonstrated, but experimental studies show that, for example, swimming performance is compromised in fish in which the coronary artery has been ligated. This paper describes a case of myocardial necrosis in harvest-size Atlantic salmon during and after transportation to the slaughterhouse. Mortality during this process reached 10% in some of the transports and affected fish showed characteristic signs of congestive cardiac failure. Histology revealed extensive myointimal proliferation in the coronary artery and patchy necrosis of the compact ventricular myocardium. Several unfavourable factors such as high water temperature, skeletal malformations and crowding all probably contributed to extra cardiac workload. To the best of our knowledge, this is the first reported field case showing a link between coronary lesions and severe cardiac pathology. PMID- 17850578 TI - Detection of infectious pancreatic necrosis virus (IPNV) from the environment in the vicinity of IPNV-infected Atlantic salmon farms in Scotland. AB - Infectious pancreatic necrosis virus (IPNV) has been isolated from mussels, sediment and surface water in the vicinity of clinically infected salmon farms, at shore bases supplying the farms and for several hundred metres distance from farms in the direction of current flow. There was evidence of decreasing prevalence of IPNV in mussels from Shetland once IPN outbreaks subsided, indicating they are an unlikely source of re-infection on farms. There was little evidence of persistence in the environment, although conclusions were complicated by the presence of IPNV on neighbouring farms 1 year after the outbreak. PMID- 17850579 TI - Fish genotype significantly influences susceptibility of juvenile rainbow trout, Oncorhynchus mykiss (Walbaum), to waterborne infection with infectious salmon anaemia virus. PMID- 17850581 TI - The immunological basis for treatment of multiple sclerosis. AB - During the last few years, the concept of multiple sclerosis (MS) as a pure inflammatory disease mediated by myelin reactive T cells has been challenged. Neither the specificity nor the mechanisms triggering or perpetuating the immune response are understood. Genetic studies have so far not identified therapeutic targets outside the HLA complex, but epidemiological and immunological studies have suggested putative pathogenetic factors which may be important in therapy or prevention, including the Epstein-Barr virus and vitamin D. Advances in the treatment of MS have been reached by manipulating the immune response where the pathogenesis of MS intersects experimental autoimmune encephalomyelitis, most recently by blocking T-cell migration through the blood-brain barrier. Antigen specific approaches are effective in experimental models driven by a focused immune response against defined autoantigens, but MS may not fit into this concept. Novel candidate autoantigens which are not constitutively expressed in the brain, such as protein alpha-B crystallin or IgG V-region idiotopes, as well as evidence of pathogenetic heterogeneity and complexity, suggest that treating MS by tolerizing the immune system against an universal MS antigen may be a fata morgana. Further characterization of MS subtypes may lead to individualized treatment. However, shared immunological features, such as intrathecal production of oligoclonal IgG, suggest that potential therapeutic targets may be shared by most MS patients. PMID- 17850582 TI - Expression of chemokine receptors CCR7 and CCR8 in the CNS during ChREAE. AB - Chemokines and their receptors are important players in organism homeostasis, development and immune response to inflammatory stimuli. It has been recently confirmed that they are also involved in the development of several autoimmune diseases. In this study, we analysed the expression of two recently identified CC chemokine receptors, CCR7 and CCR8, in the central nervous system (CNS) and in peripheral tissues during chronic relapsing experimental autoimmune encephalomyelitis (ChREAE) -- an animal model of the human demyelinating disease multiple sclerosis (MS). We observed upregulation of both chemokine receptors in the CNS during the first and second attacks of ChREAE, whereas disease remission was characterized by a lower expression of those receptors. An analysis of the kinetics of CCR7 and CCR8 expression in the CNS during the first attack of the disease showed a constant increase in the first few days after the onset of clinical signs. This expression correlated with the clinical severity of ChREAE. CCR7-positive mononuclear cells were detected mostly in perivascular inflammatory cuffs in the CNS. In peripheral tissues (the spleen and kidneys) expression of both receptors was not upregulated during active ChREAE. These findings suggest that CCR7 and CCR8 may play a significant role in the pathogenesis of EAE and probably MS. PMID- 17850583 TI - T cells from multiple sclerosis patients recognize multiple epitopes on Self-IgG. AB - The highly diversified variable regions of immunoglobulin (Ig) molecules contain immunogenic determinants denoted idiotopes. We have previously reported that T cells from multiple sclerosis (MS) patients recognize IgG from autologous cerebrospinal fluid (CSF), and mapped a T-cell epitope to an IgG idiotope. To test the ability of CSF IgG molecules to elicit a broad polyclonal T-cell response in MS, we have analysed T-cell responses in the blood and CSF against idiotope peptides spanning complementarity determining region (CDR) 3 and somatic mutations within the variable regions of monoclonal CSF IgG. Consistent with a diversified idiotope-specific T-cell repertoire, CD4(+) T cells from both patients recognized several idiotope peptides presented by HLA-DR molecules. Mutations were critical for T-cell recognition, as T cells specific for a mutated CDR1 peptide did not recognize corresponding germline-encoded peptides. One T cell clone recognized both an idiotope peptide and the B-cell clone expressing this idiotope, compatible with endogenous processing and presentation of this idiotope by B cells. These results suggest that mutated CSF IgG from MS patients carry several T-cell epitopes, which could mediate intrathecal IgG production and inflammation in MS through idiotope-driven T-B-cell collaboration. PMID- 17850584 TI - Differential locomotion of long- and short-term IL-2-activated murine natural killer cells in a model matrix environment. AB - Tumour infiltration by activated natural killer (A-NK) cells is a pre-requisite for tumour eradication by adoptive NK cell transfer. Extravasated A-NK cells do not always succeed in reaching the crucial target cell conjugation. Therefore, we wished to study A-NK cell locomotion and interactions with melanoma cells in a matrix environment (Matrigel) by electron, confocal and fluorescence microscopy. Two distinct patterns of A-NK cell-mediated matrix disintegration were revealed during incubation of tumour cells and A-NK cells in Matrigel: (1) A-NK cells pre cultured for 5 days altered the homogeneous texture of the Matrigel, an initial microporous appearance became a loose filamentous meshwork by 24 h. Matrix degrading protease inhibitors could not fully prevent this, but could delay the process; and (2) A-NK cells pre-cultured for 6 days or more, instead formed large excavations in the Matrigel leaving the remaining matrix less affected compared to the effects by the younger A-NK cells. By histochemical staining with Cupromeronic Blue, the excavations were shown to contain proteoglycan material. Protease inhibitors had no discernable effect on the development of the excavations. The conspicuous capacity of A-NK cells to disintegrate extracellular matrix and the formation of large excavations seems only partially to depend on matrix-degrading proteases. Formation of extracellular proteoglycan material is suggested to facilitate A-NK cell locomotion within a matrix environment. PMID- 17850585 TI - Participation of FLIP, RIP and Bcl-x(L) in Fas-mediated T-cell death. AB - Apart from the conventional Fas signalling pathway, alternative pathways including the mitochondrial caspase-dependent and RIP-mediated cell death routes have been proposed to operate during Fas-mediated cell death. To evaluate the contribution of different Fas signalling pathways, mice overexpressing FLIP(L), Bcl-x(L), a kinase-deficient form of RIP (RIPDeltakin) or combinations thereof were generated by retroviral gene transfer of haematopoietic stem cells. Such mice did not show overt abnormalities in haematopoietic development, defects in thymic deletion, accumulation of double-negative T cells or signs of autoimmunity. Fas-mediated death of mitogen-activated T cells was caspase dependent and could be blocked by FLIP(L) overexpression only with the minor involvement of Bcl-x(L) or RIPDeltakin inhibitable pathways. Fas-mediated death of resting CD4(+) and CD8(+) T cells was mainly caspase dependent but could only partly be blocked by FLIP(L) overexpression. Both Bcl-x(L) or RIPDeltakin expression resulted in partial protection of CD8(+) T cells against Fas-mediated cell death. These results indicate that yet uncharacterized signalling pathways from the Fas receptor are critically involved in lymphoproliferative and autoimmune disease observed in lpr mice and autoimmune lymphoproliferative syndrome patients. PMID- 17850586 TI - Demonstration of in vivo expression of a hypothetical open reading frame (ORF-14) encoded by the RD1 region of Mycobacterium tuberculosis. AB - Previously we identified a novel antigenic open reading frame (ORF), designated as ORF-14, on the RD1 region of Mycobacterium tuberculosis that was not originally predicted by Mahairas or by annotation of the M. tuberculosis H37 Rv genome. Here we show that anti-ORF-14 antibodies either from mice immunized with recombinant ORF-14 protein or isolated from serum samples from tuberculosis patients, react with a protein in culture filtrate but not in cytoplasmic or cell wall fractions from M. tuberculosis. Our data indicate that the ORF-14 protein is expressed as a secreted protein, representing one more secreted protein antigen not previously identified by genomics. PMID- 17850587 TI - Effects of LT-K63 and CpG2006 on phenotype and function of murine neonatal lymphoid cells. AB - The immature state of the immune system of neonates makes them vulnerable to infectious agents, including Streptococcus pneumoniae. The aim of our study was to analyse and compare the effects of Escherichia coli heat-labile enterototoxin (LT)-K63 and CpG2006 on cells and key molecules of the neonatal immune system, using a previously established immunization model with pneumococcal polysaccharide of serotype 1 conjugated to tetanus toxoid (TT) (Pnc1-TT). The cellular response was evaluated by measuring cytokine secretion and proliferation upon in vitro stimulation with TT, the protein moiety of Pnc1-TT, and antibody (Ab) to both the polysaccharide (PS) and protein parts of the vaccine were measured by enzyme-linked immunosorbent assay (ELISA). Antigen (Ag)-presenting and co-stimulatory capacity of neonatal B-cells was evaluated by staining for major histocompatibility complex (MHC)II, CD80, CD86 and CD40. The results showed that both LT-K63 and CpG2006 significantly enhanced the neonatal Ab response to Pnc1-TT. Spleen cells from mice receiving LT-K63 showed enhanced proliferation and interferon (IFN)-gamma, interleukin (IL)-4, IL-5 and IL-10 secretion upon TT stimulation, whereas cells from mice receiving CpG2006 could only enhance IL-10 secretion. LT-K63 and to a lesser extent CpG2006 enhanced the capacity of B-cells to up-regulate the expression of co-stimulatory and activation markers compared with those of mice receiving Pnc1-TT alone. Thus, we conclude that LT-K63 markedly improves T-cell activation whereas the direct adjuvant effect of CpG2006 on neonatal B-cells may partly compensate for lower T-cell help resulting in enhanced neonatal Ab responses to both the TT and PS parts of the vaccine by both adjuvants. PMID- 17850588 TI - Agonistic anti-4-1BB antibody promotes the expansion of natural regulatory T cells while maintaining Foxp3 expression. AB - The engagement of the 4-1BB (CD137) co-stimulatory pathway promotes the activation and proliferation of conventional CD4(+) T and CD8(+) T cells, but the role of 4-1BB co-stimulation in CD4(+) CD25(+) regulatory T cells (Treg) is less clear. In particular, whether 4-1BB stimulation affects the expression of Foxp3, a master gene for Treg, is unknown. This study demonstrates that co-stimulation of 4-1BB engaged by an agonistic antibody promotes the proliferation of Treg in a dependent manner of low-concentration interleukin-2 in vitro. The 4-1BB-expanded Treg maintain Foxp3 expression and their ability to suppress conventional CD4(+) T cells and their feature to produce no interleukin-2. However, the 4-1BB expanded Treg produce increased levels of interferon-gamma, whose significance is unknown. Thus, 4-1BB co-stimulation plays a role in the expansion of functional CD4(+) CD25(+) Treg cells without adversely affecting their suppressive activity. PMID- 17850589 TI - Capture of membrane components via trogocytosis occurs in vivo during both dendritic cells and target cells encounter by CD8(+) T cells. AB - Cytotoxic T lymphocytes recently stimulated by antigen-presenting cells (APC) display major histocompatibility class (MHC) I and II molecules inherited from APC. We have previously reported that, in vitro, transfer of MHC molecules and several other proteins occurs through trogocytosis, i.e. the active acquisition of target cell membrane fragments by T lymphocytes. Here, using the model of viral antigen LCMVgp33-41 recognition in transgenic P14 mice, we show that CD8(+) T cells perform trogocytosis in vivo, as detected by the capture of biotin- or fluorescence-labeled components of the APC surface. Trogocytosis occurs during interactions of CD8(+) T cells with at least two kinds of cells: target cells and dendritic cells (DC). In lymph nodes, CD8(+) T cells having performed trogocytosis with DC express the CD69 activation marker indicating that trogocytosis detects recently activated cells. Taken together, our findings suggest that trogocytosis may be a new in vivo marker of the recent interaction between a CD8(+) T cell and its cellular partners or targets. PMID- 17850590 TI - In active chronic rheumatoid arthritis, dipeptidyl peptidase IV density is increased on monocytes and CD4(+) T lymphocytes. AB - The effect of low-dose methotrexate (MTX) treatment on the CD26 density on circulating monocytes and CD4(+) T lymphocytes or levels of soluble CD26 (sCD26) has not yet been described in rheumatoid arthritis (RA). While CD26 in T lymphocytes is involved in the activation and proliferation of T lymphocytes, little is known of the role of CD26 in monocytes as it has only recently been localized to monocytes. We analysed the CD26 density by flow cytometry and levels of sCD26 in plasma before initiation of MTX treatment and 12 weeks later. This was done on 34 RA patients fulfilling the 1987 American College of Rheumatology (ACR) criteria followed for 16 weeks after starting MTX treatment. CD26 density on monocytes was increased in RA patients compared with healthy controls before MTX treatment (P < 0.01). After 12 weeks of MTX treatment, the CD26 density on monocytes decreased significantly in the ACR-50% group (P = 0.03), but not in the ACR-20% and the non-responder group (P = 0.15 and 0.87). The increased CD26 density on CD4(+) T lymphocytes (P < 0.01) was unaffected by the reduction in disease activity in relation to MTX treatment. The percentage of monocytes and CD4(+) T lymphocytes among peripheral blood circulating mononuclear cells did not change during MTX treatment. No effect of MTX treatment was observed on the plasma levels of sCD26. Active chronic RA is characterized by enhanced CD26 density on circulating monocytes and CD4(+) T lymphocytes. MTX treatment decreased CD26 density on monocytes in the ACR-50% responder group and was associated with decreased disease activity. The enhanced CD26 density on CD4(+) T lymphocytes was uninfluenced by MTX treatment. PMID- 17850591 TI - Biological variation in circulating levels of mannan-binding lectin (MBL) and MBL associated serine protease-2 and the influence of age, gender and physical exercise. AB - Mannan-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) are central components of the MBL pathway of complement activation, and may have potential as clinical biomarkers in colorectal cancer (CRC). Prior to clinical usage, knowledge of the biological variations of the molecules is needed. We here investigate variations of MBL and MASP-2 in healthy persons over time and in relation to gender, age and physical activity. MBL and MASP-2 concentrations were determined in serum from healthy adults over a 3-week period and this was repeated 6 months later (n = 32); during a 24-h period (n = 16); and in relation to physical exercise (n = 14). Concentrations in serum and plasma were compared (n = 198). No significant variation over 6 months and no circadian variation was found for MBL (P = 0.39 and P = 0.34 respectively) or MASP-2 (P = 0.54 and P = 0.55). Physical exercise did not affect the levels (P > 0.8). Serum and plasma levels were only marginally different, and were independent of age and gender. Circulating levels of MBL and MASP-2 are stable over time in healthy individuals, which is advantageous for their potential application as biomarkers. PMID- 17850592 TI - Antigen-specific T-cell immunity in multiple myeloma patients is restored following high-dose therapy: implications for timing of vaccination. AB - The present study analyses the influence of high-dose chemotherapy (HD) and autologous stem cell transplantation on natural and vaccine induced specific immunity in multiple myeloma patients. Peripheral blood was collected from six multiple myeloma (MM) patients at serial time points in connection with treatment and during a follow-up period of 3 months. T-cell response to cytomegalovirus (CMV), varicella zoster virus (VZV) and tetanus toxoid (TT) was determined by flow cytometry analysis for CD69, TNFalpha, IFNgamma, IL-4 expression and cell proliferation. At diagnosis and prior to induction chemotherapy TNFalpha expressing T cells in 5/6 patients were found specific for CMV, 3/6 for VZV and 4/6 for TT. Serial analyses during treatment conclude impaired immune response, however, 3 months post-transplantation all but one patient had regained cytokine expressing CD8(+) T cells specific for CMV, VZV and TT. The highest percentages of cytokine responding T cells were observed after stimulation with CMV antigen. A striking observation was the low cytokine reactivity (close to zero) measured in G-CSF mobilized blood at the time of leukapheresis. In spite of a general reduction of the CD4/CD8 ratio following transplantation, recovery of antigen specific CD4(+) T cells reactivity generally occurred prior to CD8(+) recovery and often to a higher level. In conclusion, the study demonstrates that natural as well as vaccine induced specific immunity present prior to HD was regained after stem cell transplantation, hence identifying a possible window for future vaccination trials. PMID- 17850593 TI - Efficacy of anti-CD20 treatment in patients with rheumatoid arthritis resistant to a combination of methotrexate/anti-TNF therapy. AB - Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and destruction. B cells play important role in modulating immune responses in RA. In the present study we assessed the impact of the B cell targeting as a third line treatment option. Forty-six patients with established erosive RA non-responding to combination treatment with DMARDs and TNF-alpha inhibitors were treated with anti-CD20 antibodies (rituximab). Rituximab was given intravenously once weekly on four occasions. All patients continued with the previous DMARD. Patients were followed by DAS28, levels of circulating B cells, frequency of immunoglobulin producing cells, immunoglobulins, and rheumatoid factor levels during the period of 12-58 months. Clinical improvement was achieved in 34 of 46 patients (73%) supported by a significant reduction in DAS28 (from 6.04 to 4.64, P < 0.001). Infusion of rituximab resulted in the elimination of circulating B cells in all but one patient. Within 12 months follow-up, B cells returned to circulation in 86% of patients. Fifty-three percent of the patients were successfully retreated with rituximab or re-started with anti-TNF-alpha treatment. Of the 11 non responders, five were retreated with anti-CD20 within 2 months, four of them with success, four patients received TNF-alpha inhibitors, the remaining two patients received an additional DMARD. Most of the RA patients resistant to TNF-alpha inhibitors may be effectively treated with anti-CD20 antibodies. The treatment is well tolerated and may be used repeatedly in the same patient and potentially increase sensitivity to previously inefficient treatment modalities. PMID- 17850594 TI - Helical cytokines and invertebrate immunity: a new field of research. PMID- 17850595 TI - Rudbeck's complaint: a 17th-century Latin letter relating to basic immunology. AB - Basic immunology can be said to have its origin in the mid-17th-century with the discovery of the peripheral lymphatics. They completed the gross anatomical picture of the lymphatic system, which is the basis for much of the immune response. Their recognition almost simultaneously by two Scandinavian anatomists led to a protracted war of words over priority of discovery, pitting a young Swedish medical student (Olof Rudbeck) against an honored Danish anatomy professor (Thomas Bartholin). In a 752-word letter in Latin, Rudbeck charged Bartholin with pre-dating a key observation, thereby giving priority of discovery to the latter. The purpose of this paper is to provide an English translation of this accusatory letter. It is a notable document in basic immunology, for it cites much of the knowledge then current in the field. And by raising the issue of priority, the letter indirectly piqued the interest of the scientific community in the lymphatic system and hastened its study. Examining the system's various functions in health and disease led to this new discipline. PMID- 17850596 TI - The genetic structure of Balkan populations of Drosophila subobscura. AB - Although Drosophila subobscura has been a model organism for European and American population geneticists, little information is available on the genetic structure of its natural populations. In this paper we report the estimates of some population parameters. We have used data from lethal allelism tests in four Balkan populations (Kamariste, Djerdap and Petnica in Serbia and Zanjic in Montenegro). In all populations, lethal genes were found to have a deleterious effect on heterozygotes. The N(e) values varied greatly from 370 (Petnica) to 19413 (Kamariste), depending on the habitat conditions and some environmental factors. Finally, gene flow between the Balkan populations was detected by the estimates of N(m) (from 4.68 in Petnica to 106.2 in Kamariste) and m (from 0.0041 in Djerdap to 0.0126 in Petnica). These results agree with those obtained in a previous study where the frequencies of allelism between populations were greater than predicted by independently arising lethal genes. PMID- 17850597 TI - Quantitative trait loci controlling cyanogenic glucoside and dry matter content in cassava (Manihot esculenta Crantz) roots. AB - Cassava (Manihot esculenta Crantz) is a starchy root crop grown in the tropics mainly by small-scale farmers even though agro-industrial processing is rapidly increasing. For this processing market improved varieties with high dry matter root content (DMC) is required. Potentially toxic cyanogenic glucosides are synthesized in the leaves and translocated to the roots. Selection for varieties with low cyanogenic glucoside potential (CNP) and high DMC is among the principal objectives in cassava breeding programs. However, these traits are highly influenced by the environmental conditions and the genetic control of these traits is not well understood. An S(1) population derived from a cross between two bred cassava varieties (MCOL 1684 and Rayong 1) that differ in CNP and DMC was used to study the heritability and genetic basis of these traits. A broad sense heritability of 0.43 and 0.42 was found for CNP and DMC, respectively. The moderate heritabilities for DMC and CNP indicate that the phenotypic variation of these traits is explained by a genetic component. We found two quantitative trait loci (QTL) on two different linkage groups controlling CNP and six QTL on four different linkage groups controlling DMC. One QTL for CNP and one QTL for DMC mapped near each other, suggesting pleiotrophy and/or linkage of QTL. The two QTL for CNP showed additive effects while the six QTL for DMC showed additive effect, dominance or overdominance. This study is a first step towards developing molecular marker tools for efficient breeding of CNP and DMC in cassava. PMID- 17850598 TI - Chromosomal evolution in the South American Nymphalidae. AB - We give the chromosome numbers of about 80 species or subspecies of Biblidinae as well as of numbers of neotropical Libytheinae (one species), Cyrestinae (4) Apaturinae (7), Nymphalinae (about 40), Limenitidinae (16) and Heliconiinae (11). Libytheana has about n=32, the Biblidinae, Apaturinae and Nymphalinae have in general n=31, the Limenitidinae have n=30, the few Argynnini n=31 and the few species of Acraeni studied have also mostly n=31. The results agree with earlier data from the Afrotropical species of these taxa. We supplement these data with our earlier observations on Heliconiini, Danainae and the Neotropical Satyroid taxa. The lepidopteran modal n=29-31 represents clearly the ancestral condition among the Nymphalidae, from which taxa with various chromosome numbers have differentiated. The overall results show that Neotropical taxa have a tendency to evolve karyotype instability, which is in stark contrast to the otherwise stable chromosome numbers that characterize both Lepidoptera and Trichoptera. PMID- 17850599 TI - Genetic diversity of Tunisian figs (Ficus carica L.) as revealed by nuclear microsatellites. AB - The present study portrays the achievement of the genetic polymorphism surveying and the establishment of an ecotypes identification key on the basis of simple sequence repeats data. Seventy-two Tunisian fig ecotypes in situ and ex situ conserved were analyzed using six microsatellite loci. A total of 58 alleles and 124 genotypes were revealed and permitted to evidence high degree of genetic diversity mainly explained at the intra group level. Cluster analysis based on genetic distances proved that a typical continuous genetic diversity characterizes the local germplasm. In addition, the microsatellite multilocus genotyping has permitted to unambiguously distinguish 70 well-defined ecotypes (resolving power of 97.22%). Data are discussed in relation with the reliability of the used markers to check the conformity of the plant material and to rationally manage the conservation of this crop. PMID- 17850600 TI - Cytogenetics of Danish species of Barbarea (Brassicaceae): chromocentres, chromosomes and rDNA sites. AB - Seventeen Danish accessions of five taxa of Barbarea, i.e. B. stricta, B. verna, B. intermedia and B. vulgaris ssp. vulgaris and ssp. arcuata including the two morphologically and biochemically differentiated P(pubescent)- and G(glabrous) types, and 4 P-xG-type hybrids were analysed cytologically using fluorescent in situ hybridization (FISH) and AgNO(3)-staining. The number of chromocentres varied among nuclei of somatic interphases (generally+/-2) centred around 18 in the P-type of B. vulgaris ssp. arcuata, and around 16 in the G-type, and in the other materials. The observations suggest preponderant chromosome numbers of 2n=18 and 2n=16 in root-tip cells. Chromosome numbers of metaphases supported the idea. In situ hybridization demonstrated the presence of a maximum of two rDNA sites in B. intermedia, four sites in B. stricta and B. vulgaris ssp. vulgaris, and six sites in a P-xG-type hybrid of ssp. arcuata and in B. verna. P- and G types of B. vulgaris ssp. arcuata both had accessions with four and six rDNA sites revealing polymorphism for the character. The sites differed pairwise in size in the taxa except in the P-type. P-type nuclei had peak numbers of four rDNA sites. Nuclei of other taxa had peak numbers of 2. In nuclei with six sites, one very small pair showed no transcriptional activity. Major rDNA sites presented a low frequency of association. The number of stronger rDNA signals agreed with the observation of maximally 2 AgNO(3)-stained nucleoli in B. intermedia and 3 or 4 nucleoli in the other taxa indicating 2 and 4 nucleolus organizing chromosomes in the genomes, respectively. PMID- 17850601 TI - Cigarette smoking and periodontal disease among 32-year-olds: a prospective study of a representative birth cohort. AB - BACKGROUND: Smoking is recognized as the primary behavioural risk factor for periodontal attachment loss (AL), but confirmatory data from prospective cohort studies are scarce. AIM: To quantify the association between cigarette smoking patterns and AL by age 32. METHODS: Periodontal examinations were conducted at ages 26 and 32 in a longstanding prospective study of a birth cohort born in Dunedin (New Zealand) in 1972/1973. Longitudinal categorization of smoking exposure was undertaken using data collected at ages 15, 18, 21, 26 and 32. RESULTS: Complete data were available for 810 individuals of whom 48.9% had ever smoked (31.5% were current smokers). Compared with never-smokers, long-term smokers (and other age-32 smokers) had very high odds ratios (ORs of 7.1 and 5.7, respectively) for having 1 +sites with 5 +mm AL, and were more likely to be incident cases after age 26 (ORs of 5.2 and 3.2, respectively). Two-thirds of new cases after age 26 were attributable to smoking. There were no significant differences in periodontal health between never-smokers and those who had quit smoking after age 26. CONCLUSIONS: Current and long-term smoking in young adults is detrimental to periodontal health, but smoking cessation may be associated with a relatively rapid improvement in the periodontium. PMID- 17850602 TI - Effect of non-surgical periodontal therapy on clinical and immunological response and glycaemic control in type 2 diabetic patients with moderate periodontitis. AB - OBJECTIVES: The purpose of this study was to compare the local efficacy of nonsurgical periodontal therapy between type 2 diabetic and non-diabetic patients and the effect of periodontal therapy on glycaemic control. BACKGROUND: A complex two-way relationship exists between diabetes mellitus and periodontitis. MATERIALS AND METHODS: After selection, 20 subjects (10 diabetic and 10 non diabetic) underwent baseline examination, periodontal clinical study and biochemical analysis of gingival crevicular fluid (GCF). After the pre-treatment phase, subgingival scaling and root planing were performed. Subsequently, all subjects continued the maintenance programme and were re-examined at 3 and 6 months. RESULTS: Diabetic and non-diabetic subjects responded well after therapy, showing a very similar progression during the follow-up period. Both groups showed clinically and immunologically significant improvements. Significant reductions were also found in the total volume of GCF and levels of interleukin 1beta and tumour necrosis factor-alpha. Diabetic subjects showed an improvement in their metabolic control. The change in glycosylated haemoglobin (HbA(1C)) was statistically significant at 3 and 6 months. CONCLUSIONS: The clinical and immunological improvements obtained were accompanied by a significant reduction in HbA(1C) values in type 2 diabetic subjects. Larger studies are needed to confirm this finding and establish whether periodontal therapy has a significant effect on glycaemic control. PMID- 17850603 TI - A life-course approach to assess psychosocial factors and periodontal disease. AB - BACKGROUND: Several models have been used to suggest the role of psychosocial factors in periodontal disease. None have adopted the life-course approach, which emphasizes the importance of exposures over time and at critical points of a person's life. OBJECTIVE: To investigate the relationship between psychosocial factors at two periods of life and periodontal diseases in Brazilian adult females. MATERIAL AND METHODS: The study design was a cross-sectional survey of 330 women randomly selected from a larger sample of mothers whose children participated in a study on chronic oral disease using a life-course framework. Each woman was clinically assessed for the presence of periodontal disease. An interview collected information on socioeconomic, behavioural and family-related factors at two periods of the participant's life (childhood and adulthood). The main outcome variable was loss of periodontal attachment. Data analysis used logistic regression. RESULTS: High levels of periodontal disease were predicted by <4 years of education, past and present smoking, high levels of paternal discipline in childhood and low levels of emotional support in adulthood. The influence of childhood factors was not attenuated by adulthood circumstances. CONCLUSION: Psychosocial factors in childhood and adulthood were associated with high levels of periodontal disease in adulthood. PMID- 17850604 TI - Periodontal conditions in Swiss army recruits: a comparative study between the years 1985, 1996 and 2006. AB - AIM: To compare the periodontal conditions of Swiss Army recruits in 2006 with those of previous surveys in 1996 and 1985. MATERIAL AND METHODS: A total of six hundred and twenty-six Swiss Army recruits were examined for their periodontal conditions, caries prevalence, stomatological and functional aspects of the masticatory system and halitosis. In particular, this report deals with demographic data, the assessment of plaque index (PlI), gingival index (GI) and pocket probing depth (PPD). RESULTS: Two per cent of all teeth were missing, resulting in a mean of 27.44 teeth per subject, and 77% of the missing teeth were the result of pre-molar extractions due to orthodontic indications. The mean PlI and GI were 1.33 and 1.23, respectively. On average, 27% of the gingival units bled on probing. The mean PPD was 2.16 mm (SD 0.64). Only 3.8% of the recruits showed at least one site of PPD > or = 5 mm, and 1.4% yielded more than one site with PPD > or = 5 mm. In comparison with previous, this survey yielded lower bleeding on probing (BOP) percentages than in 1985, but slightly higher scores than in 1996. This may be attributed to increased PlI scores in 2006. However, PPD remained essentially unaltered from 1996 to 2006 after having improved significantly from 1985. CONCLUSION: A significant improvement of the periodontal conditions of young Swiss males was demonstrated to have taken place between 1985 and 1996, but no further changes during the last decade were noticed. PMID- 17850605 TI - Trends in periodontal health among 35-year-olds in Oslo, 1973-2003. AB - AIM: The aim of the present study was to describe trends in periodontal health and oral hygiene using data available from four epidemiological studies on 35 year-olds in Oslo performed from 1973 to 2003. MATERIAL AND METHODS: Periodontal status of randomly selected 35-year-olds was assessed clinically and radiographically. Clinical registrations were based on the Community Periodontal Index of Treatment Needs (CPITN) and the Simplified Oral Hygiene Index. In addition, the proportion of individuals with marginal bone loss was assessed using available orthopantomograms. RESULTS: The proportion of persons with CPITN score 4 (one or more pockets > or = 6 mm) decreased from 21.8% in 1984 to 8.1% in 2003. In addition, the mean number of sextants with deep pockets per person was considerably lower in 2003 than previously. The proportion of persons without recorded bone loss increased from 46% in 1973 to 76% in 2003. An improvement in oral hygiene scores was also observed during this period. CONCLUSIONS: The results suggest that periodontal health and oral hygiene have been improving among 35-year-olds in Oslo during the last 30 years. PMID- 17850606 TI - Periodontopathic microorganisms in peripheric blood after scaling and root planing. AB - AIM: The objective of this study was to evaluate the frequency of periodontopathic and other subgingival anaerobic and facultative bacteria in the bloodstream following scaling and root planing (SRP). MATERIAL AND METHODS: Forty two patients with severe generalized chronic periodontitis (GChP) and generalized aggressive periodontitis (GAgP) were included in the study. Four samples of peripheric blood were drawn from the cubital vein at different times: Pre treatment: immediately before the SRP procedure (T1), immediately after treatment (T2), 15 min. post-treatment (T3) and 30 min. post-treatment (T4). In order to identify the presence of microorganisms in blood, subcultures were conducted under anaerobic conditions. RESULTS: 80.9% of the patients presented positive cultures after SRP and it occurred more frequently immediately after treatment; however, 19% of the patients still had microorganisms in the bloodstream 30 min. after the procedure. The periodontopathic microorganisms more frequently identified were Porphyromonas gingivalis and Micromonas micros. Campylobacter spp., Eikenella corrodens, Tannerella forsythensis, Fusobacterium spp. and Prevotella intermedia were isolated less often. Actinomyces spp. were also found frequently during bacteraemia after SRP. CONCLUSIONS: SRP induced bacteraemia associated with anaerobic bacteria, especially in patients with periodontal disease. PMID- 17850607 TI - Controlled-delivery chlorhexidine chip versus amoxicillin/metronidazole as adjunctive antimicrobial therapy for generalized aggressive periodontitis: a randomized controlled clinical trial. AB - BACKGROUND: Subgingival application of chlorhexidine via a controlled-delivery device (CHX chip) improves the clinical outcome of scaling/root planing (SRP) in therapy for chronic periodontitis. Generalized aggressive periodontitis (GAP) is commonly treated with SRP and adjunctive antimicrobial medication. To date, the efficacy of CHX chips in GAP therapy has not been evaluated. AIM: To compare SRP plus adjunctive CHX chip placement with SRP plus adjunctive systemic amoxicillin/metronidazole with regard to clinical efficacy in first-line therapy for GAP. MATERIAL AND METHODS: Thirty-six GAP patients were treated with SRP and randomly with either placement of CHX chips or systemic amoxicillin/metronidazole. Clinical attachment level (CAL), probing depth (PD), bleeding on probing (BoP) and suppuration (Pus) were measured at baseline, 3 and 6 months after therapy. RESULTS: CAL, PD, BoP and Pus were significantly reduced in both groups after 3 months. In the CHX chip group, PD significantly increased again between 3 and 6 months. Finally, amoxicillin/metronidazole patients presented significantly more CAL "gain", PD reduction and less remaining deep sites after 6 months. Pus remained detectable in CHX chip patients only. CONCLUSIONS: In first-line non-surgical therapy for GAP, SRP plus adjunctive systemic amoxicillin/metronidazole was more efficacious in clinically relevant measures of outcome than SRP plus adjunctive placement of CHX chips. PMID- 17850608 TI - A preliminary study of intra-pocket topical versus injected anaesthetic for scaling and root planing. AB - AIM: Compare the efficacy of topical benzocaine gel to injected lidocaine during scaling and root planing. MATERIALS AND METHODS: In each of 21 participants undergoing root planing, two dental quadrants were randomly assigned to receive topical 20% benzocaine gel delivered subgingivally (TOP) or injection anaesthesia using 2% lidocaine (INJ). Baseline, intra- and immediate post-operative pain was assessed using the Heft-Parker pain scale. Intra-subject differences (INJ-TOP) were analysed using paired t-tests and mixed models. RESULTS: Baseline and post operative pain did not differ between treatments (p>0.50). The injected anaesthetic, however, was associated with less intra-operative pain than the topical (INJ-TOP=-24.9 mm, p=0.005) Six participants required rescue (injected) anaesthesia during treatment with the topical. Eleven participants (52%) preferred topical over injected anaesthetic. Among these 11, intra-operative pain scores did not differ significantly (TOP=38.6 mm, INJ=28.4 mm, p=0.23). Among those who preferred the injected anaesthetic, intra-operative pain scores differed significantly (TOP=84.7 mm, INJ=43.8 mm, p=0.03). CONCLUSIONS: Intra pocket benzocaine gel is less effective than injected lidocaine in controlling pain during scaling and planing. Anaesthetic preference was related to the level of pain experienced during treatment with the topical. Larger studies are needed to confirm these findings. PMID- 17850609 TI - Comparison of gingival blood flow during healing of simplified papilla preservation and modified Widman flap surgery: a clinical trial using laser Doppler flowmetry. AB - AIM: This prospective randomized-controlled clinical trial compared the gingival blood flow responses following simplified papilla preservation (test) versus modified Widman flap (control). MATERIALS AND METHODS: Twenty contra-lateral upper sites with pocket depth > or = 5 mm after initial treatment in 10 chronic periodontitis patients were randomly assigned to either test or control treatment, using a split-mouth design. Laser Doppler flowmetry recordings were performed pre-operatively, following anaesthesia, immediately post-operatively and on days 1, 2, 3, 4, 7, 15, 30 and 60, at nine selected sites per flap. RESULTS: Significant ischaemia was observed at all sites following anaesthesia and immediately post-operatively. At the mucosal flap basis, a peak hyperaemic response was observed on day 1, which tended to resolve by day 4 at the test sites, but persisted until day 7 at the control sites. The buccal and palatal papillae blood perfusion presented the maximum increase on day 7 in both groups and returned to baseline by day 15. Both surgical modalities yielded significant pocket depth reduction, recession increase and clinical attachment gain. CONCLUSIONS: Periodontal access flaps represent an ischaemia-reperfusion flap model. The simplified papilla preservation flap may be associated with faster recovery of the gingival blood flow post-operatively compared with the modified Widman flap. PMID- 17850610 TI - Conceptual and methodological issues for research on tobacco-related health disparities. PMID- 17850611 TI - Identifying health disparities across the tobacco continuum. AB - AIMS: Few frameworks have addressed work-force diversity, inequities and inequalities as part of a comprehensive approach to eliminating tobacco-related health disparities. This paper summarizes the literature and describes the known disparities that exist along the tobacco disease continuum for minority racial and ethnic groups, those living in poverty, those with low education and blue collar and service workers. The paper also discusses how work-force diversity, inequities in research practice and knowledge allocation and inequalities in access to and quality of health care are fundamental to addressing disparities in health. METHODS: We examined the available scientific literature and existing public health reports to identify disparities across the tobacco disease continuum by minority racial/ethnic group, poverty status, education level and occupation. FINDINGS: Results indicate that differences in risk indicators along the tobacco disease continuum do not explain fully tobacco-related cancer consequences among some minority racial/ethnic groups, particularly among the aggregate groups, blacks/African Americans and American Indians/Alaska Natives. The lack of within-race/ethnic group data and its interactions with socio economic factors across the life-span contribute to the inconsistency we observe in the disease causal paradigm. CONCLUSIONS: More comprehensive models are needed to understand the relationships among disparities, social context, diversity, inequalities and inequities. A systematic approach will also help researchers, practitioners, advocates and policy makers determine critical points for interventions, the types of studies and programs needed and integrative approaches needed to eliminate tobacco-related disparities. PMID- 17850612 TI - Addressing tobacco-related health disparities. AB - AIMS: The aim of this review is to outline a transdisciplinary research framework for identifying, explaining and intervening to address tobacco-related health disparities (TRHD). We will show the importance of an approach that integrates the human life-cycle (developmental) and tobacco addiction cycle (behavioral) for interventions that address group-specific vulnerabilities. METHODS: The existing empirical knowledge base on tobacco-related health disparities is mapped onto a conceptual framework built around life-cycle and addiction cycle trajectories for disparate population groups. FINDINGS: Current knowledge about developmental trajectories of tobacco use is based on general population studies with minimal information on group differences. At the national level, early onset of tobacco use is associated with a high level of tobacco dependence, low number of quit attempts, long-term smoking history and tobacco-related health harm. These relationships cannot be assumed for all population groups: African Americans and Asian Americans typically have a later age of tobacco use onset compared to European Americans, yet health consequences of smoking are higher among African Americans but not Asian Americans. Even less is known about group differences in the temporal progression from smoking onset to daily smoking. Determining the time-frame from initial to regular smoking seems crucial for targeted secondary prevention, before the establishment of addictive tobacco use patterns. Group specific data characterizing the duration from daily tobacco use to a quit attempt or request for cessation treatment are also scant. CONCLUSIONS: A comprehensive, integrated, transdisciplinary framework is needed to guide efforts to understand tobacco-related health disparities and to increase the effectiveness of evidence-based interventions delivered in culturally appropriate and economically practicable ways, while optimizing the balance between demand for and access to services. PMID- 17850613 TI - A biopsychosocial approach to examining tobacco-related health disparities among racially classified social groups. AB - AIMS: To articulate a broader, multi-causal model that incorporates psychosocial and environmental factors that can differ systematically across racially classified social groups (RCSGs) and impact biological pathways related to the development of tobacco-related diseases. METHODS: This paper is built upon a review of the existing scientific literature on selected biopsychosocial factors (diet/nutrition, obesity, alcoholic intake, psychosocial stress, occupational/environmental exposures and exposure to other diseases and illnesses) and tobacco use in examining the biological contributions to differences in tobacco-related health outcomes among RCSGs. FINDINGS: Recent work has focused on RCSG genetic variations as a possible explanation for differences in tobacco-related health disparities. It is argued in this paper that, given the genetic heterogeneity 'within' RCSGs, it is unlikely that across RCSG genetic variations are likely to be the major source of differences impacting biological pathways in tobacco-related health outcomes. The evidence shows that results, even at the level of within-population genetic variations, have been limited and often inconsistent. A conceptual framework is proposed to account for biological pathways related to the development of tobacco-related diseases. CONCLUSIONS: Determinants of tobacco-related health disparities are not understood clearly. The contribution of biological factors may be important. Current efforts to determine biological differences in tobacco use and related diseases among RCSGs have focused primarily on genetic variations. However, this approach has limitations. An alternative biopsychosocial framework that examines the potential biological mechanisms through which life experiences and behavior might affect tobacco use and health outcomes in these population groups is needed, including those of life-style (e.g. diet/nutrition, obesity, physical exercise, alcohol consumption), psychosocial (e.g. stress and coping), occupational/environmental exposures and the presence of other diseases/illnesses. PMID- 17850614 TI - Racially classified social group tobacco-related health disparities: what is the role of genetics? AB - Certain racially classified social groups suffer disproportionately from tobacco caused morbidity and mortality. Recent advances in genetics are leading researchers to examine variables that may account for this. However, it is critical that investigators proceed with caution and utilize transdisciplinary approaches. A number of fundamental questions might be used to stimulate consensus building in this area of science. What is race and how should its complexity be operationalized? Is it possible/likely that pharmacogenetics will allow us to match smokers with cessation strategies based on a gene-psychological profile? What are the most important conceptual and methodological issues for a research agenda in this area? PMID- 17850615 TI - Overcoming confounding of race with socio-economic status and segregation to explore race disparities in smoking. AB - AIMS: We examined the nature of racial disparities in smoking status within a sample that accounts for two major confounding factors in health disparities research--racial segregation and socio-economic status. Also, we sought to determine the generalizability of our sample. DESIGN AND SETTING: Cross-sectional study based on data from the Exploring Health Disparities in Integrated Communities Study in south-west Baltimore, MD (EHDIC-SWB) and a subsample of respondents in the 2002 National Health Interview Survey (NHIS) that was matched to EHIDC-SWB. The final matched data set sample size was 2948 adults (1474 EHDIC SWB; 1474 matched NHIS). MEASUREMENTS: Our outcome variables were life-time and current smoking status and number of cigarettes smoked daily. Independent variables include race, age gender, educational attainment and income. FINDINGS: In the adjusted models, whites had greater odds than blacks of current smoking and reported smoking more cigarettes in the EHDIC-SWB sample, but there were no race differences in current smoking status or in the number of cigarettes smoked per day in the NHIS. The prevalence rates for both life-time and current smoking were substantially greater in the EHDIC-SWB sample, but in comparisons of blacks and whites across samples we found that the magnitude of the difference between the samples was greatest for whites. CONCLUSIONS: Unadjusted national estimates of race disparities as reported in national reports may be biased because of differential risk exposure among people of different race groups. Race differences in social and environmental contexts account partially for racial differences in smoking patterns. PMID- 17850616 TI - How reliable and valid is the Brief Sensation Seeking Scale (BSSS-4) for youth of various racial/ethnic groups? AB - AIMS: To assess the reliability and validity of the Brief Sensation Seeking Scale BSSS-4 by race/ethnicity. DESIGN: Six waves of nationally representative, cross sectional, Legacy Media Tracking Survey (LMTS) data. Analyses are based on a sample size of 24 328 individuals. Response rates for the individual survey administrations range from 60% to 30%. SETTING: Data were collected by telephone, from April 2001 to January 2004. PARTICIPANTS: Youth, aged 12-17 years, who completed the LMTS. MEASUREMENTS: Sensation seeking was measured using the four item scale, BSSS-4, published by Stephenson et al. in 2003. A series of items from the LMTS was used to measure youth intention to smoke and smoking behavior. FINDINGS: Mean sensation seeking scores increased as the risk for established smoking increased. African American youth who are open to smoking or have experimented with cigarettes had lower mean sensation seeking scores than their white and Hispanic counterparts. Coefficient alpha and average corrected item total correlations suggest that the BSSS-4 is a less reliable measure of sensation seeking for African American youth compared to white and Hispanic youth. CONCLUSIONS: The BSSS-4 is a useful tool for identifying youth at risk for smoking; however, it is less reliable and valid for African American youth compared with other youth. Future research should investigate whether other existing sensation seeking scales are equally reliable and valid across race/ethnicity, and whether an alternative scale could or should be developed that would measure sensation seeking more effectively among African American youth. PMID- 17850617 TI - The reliability and validity of the Brief Sensation Seeking Scale (BSSS-8) with young adult Latino workers: implications for tobacco and alcohol disparity research. AB - AIM: This study investigated the reliability and validity of the Brief Sensation Seeking Scale (BSSS-8) in both English and Spanish with Latinos, the fastest growing minority group in the United States, and the correlation between sensation seeking and tobacco and alcohol use. DESIGN: Cross-sectional survey, computer-assisted telephone interviews (CATI). SETTING: Dallas and Houston, Texas. PARTICIPANTS: A total of 789 Latinos participated in this study. Participants were currently in the work-force, not enrolled in college, and between the ages of 18 and 30 years. MEASUREMENTS: Participants completed a self report questionnaire (in either English or Spanish) consisting of items measuring tobacco and alcohol use as well as the eight-item Brief Sensation Seeking Scale. FINDINGS AND CONCLUSIONS: For English-speaking Latino participants, the BSSS factor structure was second-order unidimensional and correlated positively with life-time cigarette use, intention to smoke in the future and amount and frequency of alcohol consumption. For Spanish-speaking Latino participants, a four-subfactor solution for the BSSS provided the best fit to the data although correlations between the four subscales and cigarette use were small. PMID- 17850618 TI - Sensation seeking: a commentary. AB - AIMS: To discuss some of the conceptual and methodological issues about race/ethnicity and sensation seeking not discussed fully in the two empirical papers in this issue. METHODS: The authors of this commentary examined critically the papers in this issue by Vallone et al. and Stephenson et al. and asked if there were underlying or foundational issues that were ignored or not discussed adequately regarding the sensation seeking construct. After reviewing an initial list of those issues, a decision was made to discuss four of them. FINDINGS: There is inadequate attention paid to: (i) the developmental aspects of sensation seeking and the almost exclusive focus on youth; (ii) the possibility that sensation seeking is relevant primarily for initial events and not continuation, progression within and across drug classes, progression to dependence, regression, cessation and relapse; (iii) the putative multi-dimensionality of sensation seeking and the pervasive tendency of researchers to ignore the dimensions; and (iv) possible lack of validity of the construct within and across racial and ethnic groups. CONCLUSIONS: The two papers in this issue by Vallone et al. and Stephenson et al., each of which is focused on racial/ethnic differences in the relationship of sensation seeking to tobacco attitudes, intentions and tobacco use, suggest that it is time for more foundational research on the relevance of the multi-dimensional definition of the construct. The relationship of the putative dimensions to each other and to other variables, and the utility of the construct for segmenting audiences and predicting public health outcomes, is an area where more foundational research is needed. PMID- 17850619 TI - Differential impact of state tobacco control policies among race and ethnic groups. AB - AIMS: This paper describes patterns of racial and ethnic cigarette use in the United States and discusses changes in state-level tobacco control policies. Moreover, this paper reviews the existing econometric literature on racial and ethnic smoking and discusses the limitations of that research. Finally, this paper outlines an agenda for future research. METHODS: Patterns of racial and ethnic smoking and changes in state-level tobacco control policies in the United States were obtained from a variety of sources, including surveys and government and private documents and databases. After an extensive literature search was completed, the existing research was scrutinized and recommendations for much needed future research were put forth. FINDINGS: Despite the fact that certain racial and ethnic minorities bear a disproportionate share of the overall health burden of tobacco, less than a handful of econometric studies have examined the effects of state-level public policies on racial and ethnic smoking. The existing literature finds Hispanics and African Americans to be more responsive to changes in cigarette prices than whites. Only one study examined other state-level tobacco policies. The findings from that study implied that adolescent white male smoking was responsive to changes in smoke-free air laws, while adolescent black smoking was responsive to changes in youth access laws. CONCLUSIONS: While much has been learned from prior econometric studies on racial and ethnic smoking in the United States, the existing literature suffers from numerous limitations that should be addressed in future research. Additional research that focuses on races and ethnicities other than white, black and Hispanic is warranted. Furthermore, future studies should use more recent data, hold sentiment toward tobacco constant and control for a comprehensive set of tobacco policies that take into account not only the presence of the laws, but also the level of restrictiveness of each policy. PMID- 17850620 TI - Most Latino smokers in California are low-frequency smokers. AB - AIMS: We examine the phenomenon of low-frequency smoking (non-daily smoking or smoking G and 5370 C-->T in BRCA1 and 999del5 and 6503delTT in BRCA2, are recurrent Finnish founder mutations. These results add to the evidence of the geographical differences in distribution of Finnish BRCA1/BRCA2 mutations. This screen also provides further evidence for the presumption that the majority of Finnish BRCA1/BRCA2 founder mutations have been found and that the proportion of BRCA1/BRCA2 mutations in Finnish breast/ovarian cancer families is around 20%. PMID- 17850628 TI - Combined UGT1A1 and UGT1A7 variant alleles are associated with increased risk of Gilbert's syndrome in Taiwanese adults. AB - Gilbert's syndrome (GS) is caused by a reduction in the activity of hepatic bilirubin UDP-glucuronosyltransferase (UGT). This reduction is associated with UGT1A1*28 and UGT1A1*6 polymorphisms. Recent research also showed that carriage of UGT1A1*6 allele were significantly related with UGT1A7*3. Polymerase chain reaction-restriction fragment length polymorphism were utilized to determine UGT1A7 and UGT1A1 genes for 207 patients with GS and 207 gender/age-matched healthy controls. For the 207 healthy controls, linkage disequilibrium was observed between -57UGT1A7 and 622UGT1A7 loci (D' = 1.00 and r(2) = 1.00), 57UGT1A7 and 211UGT1A1 loci (D' = 0.72 and r(2) = 0.36), respectively. A dose response effect for number of at-risk allele of UGT1A1 and risk for GS was noted (odds ratio (OR) = 8.19 for heterozygous UGT1A1*28 genotype; OR = 124.96 for homozygous UGT1A1*28 genotype; and p for trend <0.05). Patients with combined genotypes carrying UGT1A7 variant alleles and UGT1A1 variant alleles (including UGT1A1*28 and UGT1A1*6) are associated with increased risk of GS (OR = 13.96 for patients with combined genotype carrying at least one variant allele of UGT1A1 and UGT1A7). In conclusion, the -57UGT1A7 (T>G) is highly associated with UGT1A7*3 and moderately associated with 211UGT1A1 (G>A). Certain UGT1A1/UGT1A7 combined genotypes are risk factors of GS. PMID- 17850629 TI - Identification of proximal 1p36 deletions using array-CGH: a possible new syndrome. AB - Monosomy 1p36 is the most common terminal deletion syndrome with an estimated occurrence of 1:5000 live births. Typically, the deletions span <10 Mb of 1pter 1p36.23 and result in mental retardation, developmental delay, sensorineural hearing loss, seizures, cardiomyopathy and cardiovascular malformations, and distinct facies including large anterior fontanel, deep-set eyes, straight eyebrows, flat nasal bridge, asymmetric ears, and pointed chin. We report five patients with 'atypical' proximal interstitial deletions from 1p36.23-1p36.11 using array-comparative genomic hybridization. Four patients carry large overlapping deletions of approximately 9.38-14.69 Mb in size, and one patient carries a small 2.97 Mb deletion. Interestingly, these patients manifest many clinical characteristics that are different from those seen in 'classical' monosomy 1p36 syndrome. The clinical presentation in our patients included: pre- and post-natal growth deficiency (mostly post-natal), feeding difficulties, seizures, developmental delay, cardiovascular malformations, microcephaly, limb anomalies, and dysmorphic features including frontal and parietal bossing, abnormally shaped and posteriorly rotated ears, hypertelorism, arched eyebrows, and prominent and broad nose. Most children also displayed hirsutism. Based on the analysis of the clinical and molecular data from our patients and those reported in the literature, we suggest that this chromosomal abnormality may constitute yet another deletion syndrome distinct from the classical distal 1p36 deletion syndrome. PMID- 17850630 TI - Distribution and frequencies of CDH23 mutations in Japanese patients with non syndromic hearing loss. AB - Mutations in the CDH23 gene are known to be responsible for both Usher syndrome type ID (USH1D) and non-syndromic hearing loss (DFNB12), and the molecular confirmation of the CDH23 gene has become important in the diagnosis of these conditions. The present study was performed to find whether the CDH23 mutations are also responsible for non-syndromic hearing loss in patients in the Japanese population. A total of 51 sequence variants were found in 64 Japanese probands with non-syndromic sensorineural hearing impairment from autosomal recessive families. Among them, at least four missense mutations in six patients from five families were confirmed to be responsible for deafness by segregation study. All mutations detected were missense mutations, corroborating the previous reports regarding DFNB12. The present data confirmed that CDH23 mutations are frequently found and significantly responsible in Japanese. Interestingly, the CDH23 mutation spectrum in Japanese is very different from that found in Caucasians. This Japanese spectrum may be representative of those in Eastern Asian populations and its elucidation is expected to facilitate the molecular diagnosis of DFNB12 and USH1D. PMID- 17850631 TI - Non-random maternal X-chromosome inactivation associated with PHACES. AB - The acronym PHACES is used to describe the association of posterior fossa malformations, hemangiomas, arterial anomalies (cardiovascular or cerebrovascular), coarctation of the aorta and cardiac defects, eye abnormalities, and sternal or ventral defects. We report a female patient with an uncommon variant of this neurocutaneous disorder who manifested a sternal cleft; supraumbilical raphe; hemangiomas of the face, chest, and extremities; micrognathia and cerebrovascular anomalies. A literature review of PHACES patients with both sternal cleft and supraumbilical raphe showed a marked female predilection. Taken together with cases of sternal cleft, supraumbilical raphe and facial hemangiomas tabulated by Gorlin et al. (1994), 91% (40/44) of patients are female. One affected male died shortly after birth. We hypothesized that the gender bias in PHACES results from mutation in an X-linked dominant gene often lethal in males, and performed X-inactivation analysis of the polymorphic androgen receptor locus in this family. We documented consistently skewed X inactivation (80%/20% in two independent analyses) in the unaffected mother and consistently random X-inactivation (47:53 and 61:39 in independent analyses) in the proband. These findings are consistent with favorably skewed X-inactivation producing a normal maternal phenotype, a phenomenon documented in X-linked dominant Rett syndrome. PMID- 17850632 TI - Molecular analysis and long-term clinical evaluation of three siblings with Alstrom syndrome. AB - Alstrom syndrome is a rare, autosomal recessive disorder characterized by a wide spectrum of clinical features including early-onset retinal degeneration leading to blindness, sensorineural hearing loss, short stature, obesity, type 2 diabetes, hyperlipidemia and dilated cardiomyopathy. Renal, hepatic and pulmonary dysfunction may occur in the later phases of the disease. The three affected sisters, from a consanguineous Turkish family, with the characteristic features of Alstrom syndrome, were clinically diagnosed in 1987 and followed for 20 years. DNA sequence analysis of ALMS1, the causative gene in Alstrom syndrome, identified a novel homozygous disease-causing mutation, c.8164C>T, resulting in a premature termination codon in exon 10 in each of the three affected sisters. Furthermore, we describe the longitudinal disease progression in this family and report new clinical findings likely associated with Alstrom syndrome, such as pes planus and hyperthyroidism. PMID- 17850633 TI - Movement and mood disorder in two brothers with Gaucher disease. AB - Gaucher disease (GD) is a lysosomal storage disorder with a wide spectrum of phenotypic presentations. We report the case histories of two adult brothers with GD who developed both parkinsonism and psychiatric symptoms. Direct sequencing and real-time polymerase chain reaction were used to establish that the patients were homozygous for mutation L444P. While parkinsonism has been described previously in GD, these patients had atypical features, including a complicated mood disorder. The comorbidity of GD and a mood disorder is a new finding, as psychiatric manifestations of GD have been described rarely. The etiology of the mental illness could be related to the processes contributing to the development of parkinsonism. PMID- 17850634 TI - Pure subtelomeric microduplications as a cause of mental retardation. AB - Submicroscopic subtelomeric aberrations are a common cause of mental retardation (MR). New molecular techniques allow the identification of subtelomeric microduplications, but their frequency and significance are largely unknown. We determined the frequency of subtelomeric, pure microduplications in a cohort of 624 patients with MR and/or multiple congenital anomalies using multiplex ligation dependent probe amplification (MLPA) and delineated the identified microduplications using array based comparative genomic hybridization (array CGH). In 11 patients, MLPA revealed a subtelomeric duplication without a concurrent deletion. Additional fluorescence in situ hybridization studies and parental analyses showed that three had occurred de novo: one duplication 5q34qter (12.7 Mb), one duplication 9q34.13qter (7.2 Mb) and one duplication 9p24.2pter (4.1 Mb). Five microduplications (9p, 11q, 12q, 15q and 16p) appeared to be inherited from an unaffected parent, while in three cases (9p, 12p and 17p) the parents were not available for testing. Based on our findings and data from the literature, the three de novo duplications were the only ones likely to be disease-causing, leading to a frequency of pathogenic subtelomeric, pure microduplications of 0.5%. Our study shows that subtelomeric microduplications are an infrequent cause of MR and that additional clinical and family studies are required to assess their clinical significance. PMID- 17850635 TI - Auditory pathology in cri-du-chat (5p-) syndrome: phenotypic evidence for auditory neuropathy. AB - 5p-(cri-du-chat syndrome) is a well-defined clinical entity presenting with phenotypic and cytogenetic variability. Despite recognition that abnormalities in audition are common, limited reports on auditory functioning in affected individuals are available. The current study presents a case illustrating the auditory functioning in a 22-month-old patient diagnosed with 5p- syndrome, karyotype 46,XX,del(5)(p13). Auditory neuropathy was diagnosed based on abnormal auditory evoked potentials with neural components suggesting severe to profound hearing loss in the presence of cochlear microphonic responses and behavioral reactions to sound at mild to moderate hearing levels. The current case and a review of available reports indicate that auditory neuropathy or neural dys synchrony may be another phenotype of the condition possibly related to abnormal expression of the protein beta-catenin mapped to 5p. Implications are for routine and diagnostic specific assessments of auditory functioning and for employment of non-verbal communication methods in early intervention. PMID- 17850636 TI - Negative genetic neonatal screening for cystic fibrosis caused by compound heterozygosity for two large CFTR rearrangements. PMID- 17850637 TI - Mosaic paternally derived inv dup(15) may partially rescue the Prader-Willi syndrome phenotype with uniparental disomy. PMID- 17850638 TI - Gene dosage influences the age at onset of SCA2 in a family from southern Italy. PMID- 17850639 TI - Germinal mosaicism in Simpson-Golabi-Behmel syndrome. PMID- 17850640 TI - Ethanol interactions with calcium-dependent potassium channels. AB - In most neurons and other excitable cells, calcium-activated potassium channels of small (SK) and large conductance (BK; MaxiK) control excitability and neurotransmitter release. The spontaneous activity of dopamine neurons of the ventral tegmental area is increased by ethanol. This ethanol excitation is potentiated by selective blockade of SK, indicating that SK channels modulate ethanol stimulation of neurons that are critical in reward and reinforcement. On the other hand, ethanol directly modulates BK channel activity in a variety of systems, including rat neurohypophysial nerve endings, primary sensory dorsal root ganglia, nucleus accumbens neurons, Caenorhabditis elegans type-IV dopaminergic CEP neurons, and nonneuronal preparations, such as rat pituitary cells, cerebrovascular myocytes and human umbilical vein endothelial cells. Ethanol action on BK channels can modify neuropeptide and growth hormone release, nociception, cerebrovascular tone, and endothelial proliferation. Ethanol modulates BK channels even when the drug is evaluated using recombinant BK channel-forming alpha (slo) subunits or channel reconstitution in artificial, binary lipid bilayers, indicating that the slo subunit and its immediate lipid microenvironment are the essential targets of ethanol. Consistent with this, single amino acid slo channel mutants display altered ethanol sensitivity. Furthermore, C. elegans slo1 null mutants are resistant to ethanol-induced motor incoordination. On the other hand, Drosophila melanogaster slo null mutants fail to acquire acute tolerance to ethanol sedation. Ethanol action on slo channels, however, may be tuned by a variety of factors, including posttranslational modification of slo subunits, coexpression of channel accessory subunits, and the lipid microenvironment, resulting in increase, refractoriness, or even decrease in channel activity. In brief, both SK and BK channels are important targets of ethanol throughout the body, and interference with ethanol effects on these channels could form the basis for novel pharmacotherapies to ameliorate the actions or consequences of alcohol abuse. PMID- 17850641 TI - Acoustic startle at baseline and during acute alcohol withdrawal in replicate mouse lines selectively bred for high or low alcohol preference. AB - BACKGROUND: Previous data in both rat and mouse genetic models suggest that there is a genetic relationship between acute alcohol withdrawal responses and innate alcohol drinking behavior. The purpose of the present study was to examine whether acute alcohol withdrawal responses, as measured by acoustic startle and prepulse inhibition (PPI) of acoustic startle, may be genetically related to innate differences in alcohol preference in 2 mouse lines selectively bred for high (HAP1 and HAP2) or low (LAP1 and LAP2) alcohol preference. Line differences in startle responses at baseline, prior to alcohol or saline treatment, were also measured. METHODS: Alcohol-naive, male and female HAP1 (n = 35) and LAP1 (n = 32) and HAP2 (n = 43) and LAP2 (n = 40) mice were tested under baseline conditions and during withdrawal from a single injection of 4.0 g/kg alcohol or equal volume of saline at 4, 8, and 12 hours post-injection. RESULTS: On most trial types, baseline startle responses and PPI were greater in both HAP lines than in both LAP lines, and startle responses were greater in males than in females. During acute alcohol withdrawal, both male LAP lines, and LAP1 females, showed reduced startle responses at the 4-hour time point during acute alcohol withdrawal. In contrast, both HAP1 males and females showed a trend toward enhanced startle at 4 hours in withdrawal. No clear differences in PPI during withdrawal were evident. CONCLUSIONS: These findings indicate good evidence for a genetic relationship between greater baseline acoustic startle responses and PPI and high alcohol preference. Modest support for a genetic correlation between low alcohol preference and reduced startle responses at 4 hours in withdrawal was found in male mice. The suppression in acoustic startle during acute alcohol withdrawal in male LAP lines but not in male HAP lines suggests that a genetic propensity toward low alcohol preference may be related to greater sensitivity to alcohol as measured by acoustic startle responses during acute alcohol withdrawal. PMID- 17850642 TI - Family-based association analyses of alcohol dependence phenotypes across DRD2 and neighboring gene ANKK1. AB - BACKGROUND: There is an extensive and inconsistent literature on the association of the dopamine D2 receptor gene (DRD2) with alcohol dependence. Conflicting results have been attributed to differences in the severity of the alcohol dependence phenotype across studies, failure to exclude related disorders from comparison groups, and artifacts of population-stratification. Recently the genetic polymorphism most widely analyzed in DRD2, Taq1A, has been discovered to reside in a neighboring gene, ankyrin repeat and kinase domain containing 1 (ANKK1), located 10 kb downstream from DRD2. METHODS: To more carefully characterize evidence for association across this region, we genotyped 26 single nucleotide polymorphisms (SNPs) spanning DRD2 and ANKK1 in a sample of 219 Caucasian families (n = 1,923) from the Collaborative Study on the Genetics of Alcoholism (COGA), making this the most extensive analysis to date of association between this region and alcohol dependence. We used family-based analyses robust to population-stratification, and we made use of rich phenotypic data to analyze alcohol dependence and subtypes hypothesized in the literature to be more directly influenced by DRD2. RESULTS: We found that the evidence for association is strongest in the 5' linkage disequilibrium block of ANKK1 (that does not contain Taq1A), with weak evidence of association with a small number of SNPs in DRD2. The association in ANKK1 is strongest among the subsets of alcoholics with medical complications and with antisocial personality disorder. CONCLUSIONS: More extensive genotyping across DRD2 and ANKK1 suggests that the association with alcohol dependence observed in this region may be due to genetic variants in the ANKK1 gene. ANKK1 is involved in signal transduction pathways and is a plausible biological candidate for involvement in addictive disorders. PMID- 17850643 TI - Association of the aldehyde dehydrogenase 2 promoter polymorphism with alcohol consumption and reactions in an American Jewish population. AB - BACKGROUND: Reduction in activity of the mitochondrial aldehyde dehydrogenase 2 (ALDH2) enzyme due to genetic deficiency causes reactions related to alcohol consumption and lowers the risk of alcoholism. ALDH2*2 is the only functionally significant polymorphism of the ALDH2 gene. An additional polymorphic locus in the promoter (G to A substitution approximately 360 bp from the translation start site) may influence ALDH2 activity through effects on transcriptional activity. The A allele is predicted to be less active transcriptionally than the G allele. Therefore, we hypothesized that individuals with 1 or 2 A alleles would have exaggerated reactions to alcohol. METHODS: Fifty-three Jewish college students from a Midwestern University and 76 Jewish individuals living in a large Midwestern city (all of Ashkenazi descent) were tested for associations between ALDH2*G and ALDH2*A alleles and self-reported alcohol consumption and responses to alcohol. Genotype determination was performed using PCR and slot-blot hybridization. As alcohol drinking behavior differed substantially between the college students and the general population, as well as between males and females, the analyses were performed separately in each group. RESULTS: The frequency of the ALDH2*A allele was 0.87 in the 129 Jewish individuals tested. Among the general Jewish population, those who were homozygous for ALDH2*A drank fewer drinks per occasion than individuals who were not homozygous for the ALDH2*A allele, but did not drink significantly less frequently. When the other covariates (ADH1B genotype, gender, and population) were controlled for, there was a marginal association between ALDH2A genotype and quantity of alcohol consumed and the number of drinks consumed before feeling drowsy. CONCLUSION: This study suggests that the ALDH2*A allele status may correlate with variations in alcohol consumption patterns among Jews, independent of the effect of ADH1B genotype. PMID- 17850644 TI - Unique facial features distinguish fetal alcohol syndrome patients and controls in diverse ethnic populations. AB - BACKGROUND: Effective management of fetal alcohol spectrum disorders (FASD) is dependent on the timely and reliable diagnosis of affected individuals. There are significant diagnostic difficulties because of the reduced prominence of facial features as children age to adulthood as well as potential population or ethnic differences in the most characteristic alcohol-related facial features. METHODS: A total of 276 subjects were recruited from 4 sites (Cape Town, South Africa; Helsinki, Finland; Buffalo, New York; and San Diego, California) and completed a detailed dysmorphology evaluation to classify subjects as either fetal alcohol syndrome (FAS; 43%) or control (57%). Computerized anthropometry was employed to identify facial features that could distinguish FAS patients from controls across a wide age range and across ethnically disparate study populations. RESULTS: Subjects were placed into 1 of 4 populations based on their ancestry (Cape Coloured, Finnish Caucasian, African American, or North American Caucasian). Analyses performed in each of the 4 study populations were able to identify a unique set of variables which provided excellent discrimination between the 2 groups (FAS, control). In each study group, at least one ocular-related measurement, shortened palpebral fissure, reduced outer canthal width, or reduced inner canthal width, was included in the final classification model. CONCLUSIONS: We found measurements that reflected reduced size of the eye orbit to be a consistent feature discriminating FAS and controls across each study population. However, each population had a unique, though often overlapping, set of variables which discriminated the 2 groups, suggesting important ethnic differences in the presentation of FAS. It is possible that these differences were accentuated by the wide age distribution of the study subjects. PMID- 17850645 TI - Binge drinking in Madrid, Spain. AB - BACKGROUND: In Mediterranean countries, the information on the prevalence of binge drinking and associated socio-demographic variables is very scarce. Moreover, there are no reported data on the amount of alcohol ingested and the type of beverage consumed during drinking episodes. This study describes the prevalence and characteristics of binge drinking in the adult population of Madrid, Spain. METHODS: Data were taken from a telephone survey conducted during the period 2000 to 2005 on 12,037 persons, representative of the population aged 18 to 64 years in the Madrid Region. Binge drinking was defined as the intake of >or=80 g of alcohol in men or >or=60 g in women, during any drinking session in the preceding 30 days. In this analysis, the threshold between moderate and heavy average weekly alcohol consumption was set at 40 g/d for men and 24 g/d for women. RESULTS: Prevalence of binge drinking was 14.4% (95% confidence interval, CI: 13.5 to 15.3%) in men and 6.5% (95% CI: 5.8 to 7.1%) in women. Prevalence was higher among persons: in the youngest age group (30.8% among men and 18.2% among women aged 18 to 24 years); having the highest educational level (14.5% in male and 9.2% in female university graduates); and with a heavy average consumption of alcohol (55.3% in men and 50.0% in women). However, 3 of 4 binge drinkers of both sexes showed a moderate average consumption. Among binge-drinkers, average monthly episodes of binge drinking were 3.2 in men and 2.6 in women, with 5.4 and 2 episodes/person/year, respectively. During each episode, a mean of 119 g of alcohol was ingested by men and 83 g by women, with spirits accounting for 72% of total alcohol intake. CONCLUSIONS: Prevalence of binge drinking is high in Madrid, particularly among younger men with higher education, and heavy average alcohol consumption. Binge drinking is characterized by frequent episodes, where large amounts of alcohol are ingested, mainly from spirits. PMID- 17850646 TI - Ethanol consumption modifies dendritic cell antigen presentation in mice. AB - BACKGROUND: Alcohol consumption impairs type 1 cell-mediated adaptive immune responses both in vivo and in vitro. The present study investigated the effect of alcohol consumption on antigen-presenting cell (APC) populations and cytokine production. METHODS: BALB/c were fed ethanol-containing, pair-fed isocaloric liquid control, or solid diets for 11 days. Macrophage and dendritic cell (DC) populations were isolated by paramagenetic bead separation and used to present ovalbumin (OVA) to highly purified syngeneic CD4+ T cells derived from DO11.10 T cell receptor transgenic mice in coculture. DC isolated from diet-fed mice were also used to present OVA to highly purified CD4+ T cells derived from antigen naive DO11.10Rag2-/- mice that are devoid of memory T cells. In vitro cytokine responses, interleukin (IL) -2, IL-6, IL-12, IL-13, IL-17A, and interferon-gamma (IFN-gamma) were measured by enzyme-linked immunosorbent assay. Flow cytometry measured cell surface molecule expression. RESULTS: Alcohol consumption impairs delayed hypersensitivity responses (type 1) and enhances serum IgE levels (type 2). CD11c+ DC, but not F4/80+ macrophages, support cytokine responses by purified CD4+ T cells. CD11c+ DC derived from ethanol consuming BALB/c mice show diminished ability to support IFN-gamma responses by purified CD4+ T cells derived from DO11.10 or DO11.10Rag2-/- mice. Subset analysis indicates that of the 3 "conventional" DC subsets found in mouse spleens, CD11c+CD8(alpha)+ DCs are both responsible for OVA presentation and susceptible to the effects of ethanol. Ethanol consumption does not overtly alter the percent of splenic DC, but does increase the surface density of CD11c on these cells. Data show that cocultures containing purified CD4+ T DO11.10 cells and APC derived from alcohol-consuming mice show decreased IL-6, IL-12, IL-17A, and IFN-gamma and increased IL-13 cytokine production in response to OVA stimulation. CONCLUSIONS: Ethanol alters CD11c+CD8(alpha)+ DC function, affecting cytokines responsible for adaptive immune responses. A unifying hypothesis for the underlying mechanism(s) of ethanol's effect upon adaptive immune function is proposed. PMID- 17850647 TI - Chest wall syndrome among primary care patients: a cohort study. AB - BACKGROUND: The epidemiology of chest pain differs strongly between outpatient and emergency settings. In general practice, the most frequent cause is the chest wall pain. However, there is a lack of information about the characteristics of this syndrome. The aims of the study are to describe the clinical aspects of chest wall syndrome (CWS). METHODS: Prospective, observational, cohort study of patients attending 58 private practices over a five-week period from March to May 2001 with undifferentiated chest pain. During a one-year follow-up, questionnaires including detailed history and physical exam, were filled out at initial consultation, 3 and 12 months. The outcomes were: clinical characteristics associated with the CWS diagnosis and clinical evolution of the syndrome. RESULTS: Among 24 620 consultations, we observed 672 cases of chest pain and 300 (44.6%) patients had a diagnosis of chest wall syndrome. It affected all ages with a sex ratio of 1:1. History and sensibility to palpation were the keys for diagnosis. Pain was generally moderate, well localised, continuous or intermittent over a number of hours to days or weeks, and amplified by position or movement. The pain however, may be acute. Eighty-eight patients were affected at several painful sites, and 210 patients at a single site, most frequently in the midline or a left-sided site. Pain was a cause of anxiety and cardiac concern, especially when acute. CWS coexisted with coronary disease in 19 and neoplasm in 6. Outcome at one year was favourable even though CWS recurred in half of patients. CONCLUSION: CWS is common and benign, but leads to anxiety and recurred frequently. Because the majority of chest wall pain is left-sided, the possibility of coexistence with coronary disease needs careful consideration. PMID- 17850648 TI - Age-structured gametocyte allocation links immunity to epidemiology in malaria parasites. AB - BACKGROUND: Despite a long history of attempts to model malaria epidemiology, the over-riding conclusion is that a detailed understanding of host-parasite interactions leading to immunity is required. It is still not known what governs the duration of an infection and how within-human parasite dynamics relate to malaria epidemiology. PRESENTATION OF THE HYPOTHESIS: Immunity to Plasmodium falciparum develops slowly and requires repeated exposure to the parasite, which thus generates age-structure in the host-parasite interaction. An age-structured degree of immunity would present the parasite with humans of highly variable quality. Evolutionary theory suggests that natural selection will mould adaptive phenotypes that are more precise (less variant) in "high quality" habitats, where lifetime reproductive success is best. Variability in malaria parasite gametocyte density is predicted to be less variable in those age groups who best infect mosquitoes. Thus, the extent to which variation in gametocyte density is a simple parasite phenotype reflecting the complex within-host parasite dynamics is addressed. TESTING THE HYPOTHESIS: Gametocyte densities and corresponding infectiousness to mosquitoes from published data sets and studies in both rural and urban Cameroon are analysed. The mean and variation in gametocyte density according to age group are considered and compared with transmission success (proportion of mosquitoes infected). Across a wide range of settings endemic for malaria, the age group that infected most mosquitoes had the least variation in gametocyte density, i.e. there was a significant relationship between the variance rather than the mean gametocyte density and age-specific parasite transmission success. In these settings, the acquisition of immunity over time was evident as a decrease in asexual parasite densities with age. By contrast, in an urban setting, there were no such age-structured relationships either with variation in gametocyte density or asexual parasite density. IMPLICATIONS OF THE HYPOTHESIS: Gametocyte production is seemingly predicted by evolutionary theory, insofar as a reproductive phenotype (gametocyte density) is most precisely expressed (i.e. is most invariant) in the most infectious human age group. This human age group would thus be expected to be the habitat most suitable for the parasite. Comprehension of the immuno-epidemiology of malaria, a requisite for any vaccine strategies, remains poor. Immunological characterization of the human population stratified by parasite gametocyte allocation would be a step forward in identifying the salient immunological pathways of what makes a human a good habitat. PMID- 17850649 TI - Successful downstream application of the Paxgene Blood RNA system from small blood samples in paediatric patients for quantitative PCR analysis. AB - BACKGROUND: The challenge of gene expression studies is to reliably quantify levels of transcripts, but this is hindered by a number of factors including sample availability, handling and storage. The PAXgene Blood RNA System includes a stabilizing additive in a plastic evacuated tube, but requires 2.5 mL blood, which makes routine implementation impractical for paediatric use. The aim of this study was to modify the PAXgene Blood RNA System kit protocol for application to small, sick children, without compromising RNA integrity, and subsequently to perform quantitative analysis of ICAM and interleukin-6 gene expression.Aliquots of 0.86 mL PAXgene reagent were put into microtubes and 0.3 mL whole blood added to maintain the same recommended proportions as in the PAXgene evacuated tube system. RNA quality was assessed using the Agilent BioAnalyser 2100 and an in-house TaqMan assay which measures GAPDH transcript integrity by determining 3' to 5' ratios. qPCR analysis was performed on an additional panel of 7 housekeeping genes. Three reference genes (HPRT1, YWHAZ and GAPDH) were identified using the GeNORM algorithm, which were subsequently used to normalising target gene expression levels. ICAM-1 and IL-6 gene expression were measured in 87 Malawian children with invasive pneumococcal disease. RESULTS: Total RNA yield was between 1,114 and 2,950 ng and the BioAnalyser 2100 demonstrated discernible 18s and 28s bands. The cycle threshold values obtained for the seven housekeeping genes were between 15 and 30 and showed good consistency. Median relative ICAM and IL-6 gene expression were significantly reduced in non-survivors compared to survivors (ICAM: 3.56 vs 4.41, p = 0.04, and IL-6: 2.16 vs 6.73, p = 0.02). CONCLUSION: We have successfully modified the PAXgene blood collection system for use in small children and demonstrated preservation of RNA integrity and successful quantitative real-time PCR analysis. PMID- 17850650 TI - Salmonella induces prominent gene expression in the rat colon. AB - BACKGROUND: Salmonella enteritidis is suggested to translocate in the small intestine. In vivo it induces gene expression changes in the ileal mucosa and Peyer's patches. Stimulation of Salmonella translocation by dietary prebiotics fermented in colon suggests involvement of the colon as well. However, effects of Salmonella on colonic gene expression in vivo are largely unknown. We aimed to characterize time dependent Salmonella-induced changes of colonic mucosal gene expression in rats using whole genome microarrays. For this, rats were orally infected with Salmonella enteritidis to mimic a foodborne infection and colonic gene expression was determined at days 1, 3 and 6 post-infection (n = 8 rats per time-point). As fructo-oligosaccharides (FOS) affect colonic physiology, we analyzed colonic mucosal gene expression of FOS-fed versus cellulose-fed rats infected with Salmonella in a separate experiment. Colonic mucosal samples were isolated at day 2 post-infection. RESULTS: Salmonella affected transport (e.g. Chloride channel calcium activated 6, H+/K+ transporting Atp-ase), antimicrobial defense (e.g. Lipopolysaccharide binding protein, Defensin 5 and phospholipase A2), inflammation (e.g. calprotectin), oxidative stress related genes (e.g. Dual oxidase 2 and Glutathione peroxidase 2) and Proteolysis (e.g. Ubiquitin D and Proteosome subunit beta type 9). Furthermore, Salmonella translocation increased serum IFN gamma and many interferon-related genes in colonic mucosa. The gene most strongly induced by Salmonella infection was Pancreatitis Associated Protein (Pap), showing >100-fold induction at day 6 after oral infection. Results were confirmed by Q-PCR in individual rats. Stimulation of Salmonella translocation by dietary FOS was accompanied by enhancement of the Salmonella-induced mucosal processes, not by induction of other processes. CONCLUSION: We conclude that the colon is a target tissue for Salmonella, considering the abundant changes in mucosal gene expression. PMID- 17850651 TI - Detection of the pediocin gene pedA in strains from human faeces by real-time PCR and characterization of Pediococcus acidilactici UVA1. AB - BACKGROUND: Bacteriocin-producing lactic acid bacteria are commonly used as natural protective cultures. Among them, strains of the genus Pediococcus are particularly interesting for their ability to produce pediocin, a broad spectrum antimicrobial peptide with a strong antagonistic activity against the food-borne pathogen Listeria monocytogenes. Furthermore, there is increasing interest in isolating new bacteriocin-producing strains of human intestinal origin that could be developed for probiotic effects and inhibition of pathogenic bacteria in the gut. In this work, we typed a new strain, co-isolated from baby faeces together with a Bifidobacterium thermophilum strain, and characterized its proteinaceous compound with strong antilisterial activity. RESULTS: The newly isolated strain UVA1 was identified as a Pediococcus acidilactici by carbohydrate fermentation profile, growth at 50 degrees C and 16S rDNA sequencing. The partially purified bacteriocin was heat resistant up to 100 degrees C, active over a wide range of pH (2 to 9) and susceptible to proteolytic enzymes. The molecular weight, estimated by SDS-PAGE, was similar to that of pediocin AcH/PA-1 (4.5 kDa). P. acidilactici UVA1 harboured a 9.5-kb plasmid that could be cured easily, which resulted in the loss of the antimicrobial activity. Southern hybridization using the DIG-labelled pedA-probe established that the bacteriocin gene was plasmid borne as for all pediocin described so far. Nucleotide sequence of the whole operon (3.5 kb) showed almost 100 % similarity to the pediocin AcH/PA-1 operon. The mRNA transcript for pedA could be detected in P. acidilactici UVA1 but not in the cured derivative, confirming the expression of the pedA-gene in UVA1. Using a new real-time PCR assay, eleven out of seventeen human faecal samples tested were found to contain pedA-DNA. CONCLUSION: We identified and characterised the first pediocin produced by a human intestinal Pediococcus acidilactici isolate and successfully developed a new real-time PCR assay to show the large distribution of pedA-containing strains in baby faecal samples. PMID- 17850652 TI - A discrete Single Delay Model for the Intra-Venous Glucose Tolerance Test. AB - BACKGROUND: Due to the increasing importance of identifying insulin resistance, a need exists to have a reliable mathematical model representing the glucose/insulin control system. Such a model should be simple enough to allow precise estimation of insulin sensitivity on a single patient, yet exhibit stable dynamics and reproduce accepted physiological behavior. RESULTS: A new, discrete Single Delay Model (SDM) of the glucose/insulin system is proposed, applicable to Intra-Venous Glucose Tolerance Tests (IVGTTs) as well as to multiple injection and infusion schemes, which is fitted to both glucose and insulin observations simultaneously. The SDM is stable around baseline equilibrium values and has positive bounded solutions at all times. Applying a similar definition as for the Minimal Model (MM) SI index, insulin sensitivity is directly represented by the free parameter KxgI of the SDM. In order to assess the reliability of Insulin Sensitivity determinations, both SDM and MM have been fitted to 40 IVGTTs from healthy volunteers. Precision of all parameter estimates is better with the SDM: 40 out of 40 subjects showed identifiable (CV < 52%) KxgI from the SDM, 20 out of 40 having identifiable SI from the MM. KxgI correlates well with the inverse of the HOMA-IR index, while SI correlates only when excluding five subjects with extreme SI values. With the exception of these five subjects, the SDM and MM derived indices correlate very well (r = 0.93). CONCLUSION: The SDM is theoretically sound and practically robust, and can routinely be considered for the determination of insulin sensitivity from the IVGTT. Free software for estimating the SDM parameters is available. PMID- 17850653 TI - Integrating sequence and structural biology with DAS. AB - BACKGROUND: The Distributed Annotation System (DAS) is a network protocol for exchanging biological data. It is frequently used to share annotations of genomes and protein sequence. RESULTS: Here we present several extensions to the current DAS 1.5 protocol. These provide new commands to share alignments, three dimensional molecular structure data, add the possibility for registration and discovery of DAS servers, and provide a convention how to provide different types of data plots. We present examples of web sites and applications that use the new extensions. We operate a public registry of DAS sources, which now includes entries for more than 250 distinct sources. CONCLUSION: Our DAS extensions are essential for the management of the growing number of services and exchange of diverse biological data sets. In addition the extensions allow new types of applications to be developed and scientific questions to be addressed. The registry of DAS sources is available at http://www.dasregistry.org. PMID- 17850654 TI - Alpha6beta1 integrin expressed by sperm is determinant in mouse fertilization. AB - BACKGROUND: Based on inhibition tests, the alpha6beta1 integrin was suggested to be a sperm receptor, but further experiments using gene deletion techniques have shown that neither oocyte alpha6, nor beta1 integrin subunits were essential for mouse fertilization. RESULTS: Using Western blot analysis and immunofluorescence, we showed that the mouse sperm expresses the alpha6beta1 integrin. As for oocyte, binding of GoH3 anti-alpha6 antibody to sperm induces a specific inhibition of sperm fertilizing ability. Comparing zona-intact and zona-free eggs in fusion tests, we showed that the removal of the zona pellucida by acid treatment bypasses fertilizing oocyte alpha6beta1 integrin's function in the adhesion/fusion process. CONCLUSION: These findings show that alpha6beta1 integrin is expressed by both gametes and is functional in their membranes interaction. These results and previous reports, about fertilization of alpha6 or beta1 integrin subunits deleted oocytes by wild type sperm, suggest that the presence of alpha6beta1 integrin on one of the two gamete membranes can rescue the fertilization process. This hypothesis is further supported by the exchange of membrane fragments occurring between gametes prior to fusion that we recently reported. PMID- 17850655 TI - Presence of depression and anxiety before and after coronary artery bypass graft surgery and their relationship to age. AB - BACKGROUND: Scientific literature on depression and anxiety in patients with coronary heart disease (CHD) consistently reports data of elevated anxiety and depression scores indicating clinically relevant quantities of these psychopathological conditions. Depression is considered to be a risk factor for the development of CHD and deteriorates the outcome after cardiac rehabilitation efforts. The aim of our study was to evaluate the presence of clinically relevant anxiety and depression in patients before and after coronary artery bypass grafting (CABG). Additionally we evaluated their relationship to age because of the increasing number of elderly patients undergoing CABG surgery. METHODS: One hundred and forty-two consecutive patients who underwent CABG in our hospital were asked to fill in the "Hospital Anxiety and Depression Scale - German Version (HADS)" to measure depression and anxiety scores two days before and ten days after CABG surgery. Differences between these pre- and post-surgical scores were then calculated as means for changes, and the amount of elevated scores were appraised. In order to investigate the relationship between age and anxiety and depression, respectively, Spearman correlations between age and the difference scores were calculated. In addition, ANOVA procedures with the factor "age group" and McNemar tests were calculated. Therefore the sample was divided into four equally sized age groups. RESULTS: 25.8% of the patients were clinically depressed before and 17.5% after surgery; 34.0% of the patients were clinically anxious before and 24.7% after surgery. This overall change is not significant. We found a significant negative correlation between age and the difference between the two time points for anxiety (Spearman rho = -.218; p = 0.03), but not for depression (Spearman rho = -.128; p = 0.21). ANOVA and McNemar-Tests revealed that anxiety scores and the number of patients high in anxiety declined statistically meaningful only in the youngest patient group. Such a relationship could not be found for depression. CONCLUSION: Our data show a relationship between age and anxiety. Younger patients are more anxious before CABG surgery than older ones and show a decline in symptoms while elderly patients show hardly any change. PMID- 17850656 TI - Access, use and perceptions regarding Internet, cell phones and PDAs as a means for health promotion for people living with HIV in Peru. AB - BACKGROUND: Internet tools, cell phones, and other information and communication technologies are being used by HIV-positive people on their own initiative. Little is known about the perceptions of HIV-positive people towards these technologies in Peru. The purpose of this paper is to report on perceptions towards use of information and communication technologies as a means to support antiretroviral medication adherence and HIV transmission risk reduction. METHODS: We conducted a qualitative study (in-depth interviews) among adult people living with HIV in two community-based clinics in Peru. RESULTS: 31 HIV-positive individuals in Lima were interviewed (n = 28 men, 3 women). People living with HIV in Peru are using tools such as cell phones, and the Internet (via E-mail, chat, list-serves) to support their HIV care and to make social and sexual connections. In general, they have positive perceptions about using the Internet, cell phones and PDAs for HIV health promotion interventions. CONCLUSION: Health promotion interventions using information and communication technology tools among people living with HIV in resource-constrained settings may be acceptable and feasible, and can build on existing patterns of use. PMID- 17850658 TI - A diagnostic dilemma following risk-reducing surgery for BRCA1 mutation - a case report of primary papillary serous carcinoma presenting as sigmoid cancer. AB - BACKGROUND: Women that carry germ-line mutations for BRCA1 or BRCA2 genes are at an increased risk of developing breast, ovarian and peritoneal cancer. Primary peritoneal carcinoma is a rare tumour histologically identical to papillary serous ovarian carcinoma. Risk-reducing surgery in the form of mastectomy and oophorectomy in premenopausal women has been recommended to prevent breast and ovarian cancer occurrence and decrease the risk of developing primary peritoneal cancer. CASE PRESENTATION: We present a case report of a woman with a strong family history of breast cancer who underwent risk-reducing surgery in the form of bilateral salpingo-oophorectomy following a mastectomy for a right-sided breast tumour. Following the finding of a BRCA1 mutation, a prophylactic left sided mastectomy was performed. After remaining well for twenty-seven years, she presented with rectal bleeding and altered bowel habit, and was found to have a secondary cancer of the sigmoid colon. She was finally diagnosed with primary papillary serous carcinoma of the peritoneum (PSCP). CONCLUSION: PSCP can present many years after risk-reducing surgery and be difficult to detect. Surveillance remains the best course of management for patients with known BRCA mutations. PMID- 17850657 TI - EDISA: extracting biclusters from multiple time-series of gene expression profiles. AB - BACKGROUND: Cells dynamically adapt their gene expression patterns in response to various stimuli. This response is orchestrated into a number of gene expression modules consisting of co-regulated genes. A growing pool of publicly available microarray datasets allows the identification of modules by monitoring expression changes over time. These time-series datasets can be searched for gene expression modules by one of the many clustering methods published to date. For an integrative analysis, several time-series datasets can be joined into a three dimensional gene-condition-time dataset, to which standard clustering or biclustering methods are, however, not applicable. We thus devise a probabilistic clustering algorithm for gene-condition-time datasets. RESULTS: In this work, we present the EDISA (Extended Dimension Iterative Signature Algorithm), a novel probabilistic clustering approach for 3D gene-condition-time datasets. Based on mathematical definitions of gene expression modules, the EDISA samples initial modules from the dataset which are then refined by removing genes and conditions until they comply with the module definition. A subsequent extension step ensures gene and condition maximality. We applied the algorithm to a synthetic dataset and were able to successfully recover the implanted modules over a range of background noise intensities. Analysis of microarray datasets has lead us to define three biologically relevant module types: 1) We found modules with independent response profiles to be the most prevalent ones. These modules comprise genes which are co-regulated under several conditions, yet with a different response pattern under each condition. 2) Coherent modules with similar responses under all conditions occurred frequently, too, and were often contained within these modules. 3) A third module type, which covers a response specific to a single condition was also detected, but rarely. All of these modules are essentially different types of biclusters. CONCLUSION: We successfully applied the EDISA to different 3D datasets. While previous studies were mostly aimed at detecting coherent modules only, our results show that coherent responses are often part of a more general module type with independent response profiles under different conditions. Our approach thus allows for a more comprehensive view of the gene expression response. After subsequent analysis of the resulting modules, the EDISA helped to shed light on the global organization of transcriptional control. An implementation of the algorithm is available at http://www ra.informatik.uni-tuebingen.de/software/IAGEN/. PMID- 17850659 TI - Knowledge and use of emergency contraception among women in the Western Cape province of South Africa: a cross-sectional study. AB - BACKGROUND: Emergency contraception (EC) is widely available free of charge at public sector clinics in South Africa. At the same time, rates of teenage and unintended pregnancy in South Africa remain high, and there are few data on knowledge of EC in the general population in South Africa, as in other resource limited settings. METHODS: We conducted a cross-sectional, interviewer administered survey among 831 sexually active women at 26 randomly selected public sector clinics in the Western Cape province. RESULTS: Overall, 30% of the women had ever heard of EC when asked directly, after the method was described to them. Only 15% mentioned EC by name or description spontaneously. Knowledge of EC was independently associated with higher education, being married, and living in an urban setting. Four percent of women had ever used EC. DISCUSSION: These data suggest that knowledge of EC in this setting is more common among women of higher socioeconomic status living in urban areas. For EC to play a role in decreasing unintended pregnancy in South Africa, specific interventions are necessary to increase knowledge of the method, where to get it, and the appropriate time interval for its use before the need for EC arises. Future health promotion campaigns should target rural and low socioeconomic status communities. PMID- 17850660 TI - Expression of HPV-11 L1 protein in transgenic Arabidopsis thaliana and Nicotiana tabacum. AB - BACKGROUND: We have investigated the possibility and feasibility of producing the HPV-11 L1 major capsid protein in transgenic Arabidopsis thaliana ecotype Columbia and Nicotiana tabacum cv. Xanthi as potential sources for an inexpensive subunit vaccine. RESULTS: Transformation of plants was only achieved with the HPV 11 L1 gene with the C-terminal nuclear localization signal (NLS-) encoding region removed, and not with the full-length gene. The HPV-11 L1 NLS- gene was stably integrated and inherited through several generations of transgenic plants. Plant derived HPV-11 L1 protein was capable of assembling into virus-like particles (VLPs), although resulting particles displayed a pleomorphic phenotype. Neutralising monoclonal antibodies binding both surface-linear and conformation specific epitopes bound the A. thaliana-derived particles and - to a lesser degree - the N. tabacum-derived particles, suggesting that plant-derived and insect cell-derived VLPs displayed similar antigenic properties. Yields of up to 12 microg/g of HPV-11 L1 NLS- protein were harvested from transgenic A. thaliana plants, and 2 microg/g from N. tabacum plants - a significant increase over previous efforts. Immunization of New Zealand white rabbits with approximately 50 microg of plant-derived HPV-11 L1 NLS- protein induced an antibody response that predominantly recognized insect cell-produced HPV-11 L1 NLS- and not NLS+ VLPs. Evaluation of the same sera concluded that none of them were able to neutralise pseudovirion in vitro. CONCLUSION: We expressed the wild-type HPV-11 L1 NLS- gene in two different plant species and increased yields of HPV-11 L1 protein by between 500 and 1000-fold compared to previous reports. Inoculation of rabbits with extracts from both plant types resulted in a weak immune response, and antisera neither reacted with native HPV-11 L1 VLPs, nor did they neutralise HPV 11 pseudovirion infectivity. This has important and potentially negative implications for the production of HPV-11 vaccines in plants. PMID- 17850663 TI - The effect of different skin-ankle brace application pressures on quiet single limb balance and electromyographic activation onset of lower limb muscles. AB - BACKGROUND: Several studies have been carried out in order to investigate the effect of ankle bracing on ankle joint function and performance. However, no study so far has examined the role of skin-brace interface pressure in neuromuscular control. The aim of this study was to investigate the effect of different skin-ankle brace interface pressures on quiet single limb balance and the electromyographic (EMG) activation sequence of four lower limb muscles. METHODS: Thirty three male physical education students who volunteered to take part in the study were measured under three ankle brace conditions: i) without brace, ii) with brace and 30 kPa application pressure and iii) with brace and 60 kPa application pressure. Single limb balance (anteroposterior and mediolateral parameter) was assessed on the dominant lower limb, with open and closed eyes, on a force platform, simultaneously with the EMG recording of four lower lower limb muscles' (gastrocnemius, peroneus longus, rectus femoris and biceps femoris) activation onset. RESULTS: The results showed that overall balance (total stability parameter) was not significantly affected in any of the three ankle brace conditions. However, the anteroposterior centre of pressure excursion and centre of pressure excursion velocity were significantly increased with the application of ankle brace, both with 30 and 60 kPa application pressures. Furthermore, it was found that single limb balance was significantly worse with closed eyes compared to open eyes. EMG measurements showed that the sequence of lower limb activation onset was not affected in any of the three ankle brace application conditions. The results of this study showed that the application of an ankle brace with two different skin-brace interface pressures had no effect on overall single limb balance and the sequence of lower limb muscle activation. CONCLUSION: These findings suggest that peripheral joint receptors are either not adequately stimulated by the brace application and therefore are not able to alter the balance control strategy of the CNS, or that they play a less important role in the control of single limb balance. Further research is needed in this area with more dynamic and functional measurements, before the safe use of ankle bracing can be widely recommended. PMID- 17850661 TI - Aging impacts transcriptomes but not genomes of hormone-dependent breast cancers. AB - INTRODUCTION: Age is one of the most important risk factors for human malignancies, including breast cancer; in addition, age at diagnosis has been shown to be an independent indicator of breast cancer prognosis. Except for inherited forms of breast cancer, however, there is little genetic or epigenetic understanding of the biological basis linking aging with sporadic breast cancer incidence and its clinical behavior. METHODS: DNA and RNA samples from matched estrogen receptor (ER)-positive sporadic breast cancers diagnosed in either younger (age or= 70 years) Caucasian women were analyzed by array comparative genomic hybridization and by expression microarrays. Array comparative genomic hybridization data were analyzed using hierarchical clustering and supervised age cohort comparisons. Expression microarray data were analyzed using hierarchical clustering and gene set enrichment analysis; differential gene expression was also determined by conditional permutation, and an age signature was derived using prediction analysis of microarrays. RESULTS: Hierarchical clustering of genome-wide copy number changes in 71 ER-positive DNA samples (27 younger women, 44 older women) demonstrated two age-independent genotypes; one with few genomic changes other than 1q gain/16q loss, and another with amplifications and low-level gains/losses. Age cohort comparisons showed no significant differences in total or site-specific genomic breaks and amplicon frequencies. Hierarchical clustering of 5.1 K genes variably expressed in 101 ER-positive RNA samples (53 younger women, 48 older women) identified six transcriptome subtypes with an apparent age bias (P < 0.05). Samples with higher expression of a poor outcome-associated proliferation signature were predominantly (65%) younger cases. Supervised analysis identified cancer-associated genes differentially expressed between the cohorts; with younger cases expressing more cell cycle genes and more than threefold higher levels of the growth factor amphiregulin (AREG), and with older cases expressing higher levels of four different homeobox (HOX) genes in addition to ER (ESR1). An age signature validated against two other independent breast cancer datasets proved to have >80% accuracy in discerning younger from older ER positive breast cancer cases with characteristic differences in AREG and ESR1 expression. CONCLUSION: These findings suggest that epigenetic transcriptome changes, more than genotypic variation, account for age-associated differences in sporadic breast cancer incidence and prognosis. PMID- 17850662 TI - One-year health status outcomes of unstable angina versus myocardial infarction: a prospective, observational cohort study of ACS survivors. AB - BACKGROUND: Unstable angina (UA) patients have lower mortality and reinfarction risks than ST-elevation (STEMI) or non-ST elevation myocardial infarction (NSTEMI) patients and, accordingly, receive less aggressive treatment. Little is known, however, about the health status outcomes (angina, physical function, and quality of life) of UA versus MI patients among survivors of an ACS hospitalization. METHODS: In a cohort of 1,192 consecutively enrolled ACS survivors from two Kansas City hospitals, we evaluated the associations between ACS presentation (UA, NSTEMI, and STEMI) and one-year health status (angina, physical functioning and quality of life), one-year cardiac rehospitalization rates, and two-year mortality outcomes, using multivariable regression modeling. RESULTS: After multivariable adjustment for demographic, hospital, co-morbidity, baseline health status, and treatment characteristics, UA patients had a greater prevalence of angina at 1 year than STEMI patients (adjusted relative risk [RR] = 1.42; 95% CI [1.06, 1.90]) and similar rates as NSTEMI patients (adjusted RR = 1.1; 95% CI [0.85, 1.42]). In addition, UA patients fared no better than MI patients in Short Form-12 physical component scores (UA vs. STEMI score difference -0.05 points; 95% CI [-2.41, 2.3]; UA vs. NSTEMI score difference 1.91 points; 95% CI [-4.01, 0.18]) or Seattle Angina Questionnaire quality of life scores (UA vs. STEMI score difference -1.39 points; 95% CI [-5.63, 2.85]; UA vs. NSTEMI score difference -0.24 points 95% CI [-4.01, 3.54]). Finally, UA patients had similar rehospitalization rates as MI patients (UA vs. STEMI adjusted hazard ratio [HR] = 1.31; 95% CI [0.86, 1.99]; UA vs. NSTEMI adjusted HR = 1.03; 95% CI [0.73, 1.47]), despite better 2-year survival (UA vs. STEMI adjusted HR = 0.51; 95% confidence interval (CI) [0.28, 0.95]; UA vs. NSTEMI adjusted HR = 0.40; 95% CI [0.24, 0.65]). CONCLUSION: Although UA patients have better survival rates, they have similar or worse one-year health status outcomes and cardiac rehospitalization rates as compared with MI patients. Clinicians should be aware of the adverse health status outcome risks for UA patients and consider close monitoring for the opportunity to improve their health status and minimize the need for subsequent rehospitalization. PMID- 17850664 TI - The United States Revised Uniform Anatomical Gift Act (2006): new challenges to balancing patient rights and physician responsibilities. AB - Advance health care directives and informed consent remain the cornerstones of patients' right to self-determination regarding medical care and preferences at the end-of-life. However, the effectiveness and clinical applicability of advance health care directives to decision-making on the use of life support systems at the end-of-life is questionable. The Uniform Anatomical Gift Act (UAGA) has been revised in 2006 to permit the use of life support systems at or near death for the purpose of maximizing procurement opportunities of organs medically suitable for transplantation. Some states have enacted the Revised UAGA (2006) and a few of those have included amendments while attempting to preserve the uniformity of the revised Act. Other states have introduced the Revised UAGA (2006) for legislation and remaining states are likely to follow soon. The Revised UAGA (2006) poses challenges to the Patient Self Determination Act (PSDA) embodied in advance health care directives and individual expression about the use of life support systems at the end-of-life. The challenges are predicated on the UAGA revising the default choice to presumption of donation intent and the use of life support systems to ensure medical suitability of organs for transplantation. The default choice trumps the expressed intent in an individual's advance health care directive to withhold and/or withdraw life support systems at the end-of-life. The Revised UAGA (2006) overrides advance directives on utilitarian grounds, which is a serious ethical challenge to society. The subtle progression of the Revised UAGA (2006) towards the presumption about how to dispose of one's organs at death can pave the way for an affirmative "duty to donate". There are at least two steps required to resolve these challenges. First, physicians and hospitals must fulfill their responsibilities to educate patients on the new legislations and document their preferences about the use of life support systems for organ donation at the end-of-life. Second, a broad based societal discussion must be initiated to decide if the Revised UAGA (2006) infringes on the PSDA and the individual's right of autonomy. The discussion should also address other ethical concerns raised by the Revised UAGA (2006), including the moral stance on 1) the interpretation of the refusal of life support systems as not applicable to organ donation and 2) the disregarding of the diversity of cultural beliefs about end of-life in a pluralistic society. PMID- 17850665 TI - Use of complementary and alternative medicine by cancer patients at the University of Nigeria Teaching Hospital, Enugu, Nigeria. AB - BACKGROUND: The use of Complementary and Alternative Medicine (CAM) by cancer patients is very common and varies between populations. The referenced English literature has no local study from Africa on this subject. This study was conducted to define the prevalence, pattern of use, and factors influencing the use of CAM by cancer patients at the University of Nigeria Teaching Hospital Enugu (UNTH-E), Nigeria METHOD: Face-to-face interviews using semi-structured questionnaire were used to determine the use of CAM by cancer patients. All consenting cancer patients were interviewed as they presented at the core surgical units of the UNTH- E, from June 2003 to September 2005. RESULTS: 160 patients were interviewed; 68 (42.5%) were males and 94 (57.5%) were females. Ages ranged from 13-86 years. Breast, urogenital system, gastrointestinal system, and soft tissue cancers predominated. One hundred and four patients (65.0%) have used CAM at some time during their current cancer illness; 56 (35.0%) patients have not used any form of CAM. There were more females than males among the non CAM users. The use of CAM was not affected by age, marital status, level of education, religious affiliation, or socioeconomic status. The most frequently used CAMs were herbs (51.9%), faith/prayer healing (49.4%), aloe vera (23.1%), Forever Living Products (16.3%), medicinal tea (14.4%), and Blackstone (12.5%). Over 23% of those who used CAM were satisfied, but 68.3% were disappointed. Most users (67.3%) did not see any benefit from the CAM, but 25% could describe some specific benefits. More than 21% of users reported various unwanted effects. While 86.5% of CAM users will use orthodox medicine instead of CAM in the future, 9.6% will use the two together to help each other. Most users (79.8%) will not repeat CAM or recommend its use for cancer. The majority of patients (55.8%) did not mention their use of CAM to their doctors - mostly because the doctor did not ask. CONCLUSION: CAM use is common among cancer patients in Nigeria. Most users do not obtain the expected benefits, and adverse events are not uncommon. Every clinician in the field of oncology should ask his/her patients about the use of CAM; this knowledge will enable them to better counsel the patients. PMID- 17850666 TI - Sensitivity and specificity of tritiated thymidine incorporation and ELISPOT assays in identifying antigen specific T cell immune responses. AB - BACKGROUND: Standardization of cell-based immunologic monitoring is becoming increasingly important as methods for measuring cellular immunity become more complex. We assessed the ability of two commonly used cell-based assays, tritiated thymidine incorporation (proliferation) and IFN-gamma ELISPOT, to predict T cell responses to HER-2/neu, tetanus toxoid (tt), and cytomegalovirus (CMV) antigens. These antigens were determined to be low (HER-2/neu), moderate (tt), and robustly (CMV) immunogenic proteins. Samples from 27 Stage II, III, and IV HER-2/neu positive breast cancer patients, vaccinated against the HER-2/neu protein and tt, were analyzed by tritiated thymidine incorporation and IFN-gamma ELISPOT for T cell response. RESULTS: Linear regression analysis indicates that both stimulation index (SI) (p = 0.011) and IFN-gamma secreting precursor frequency (p < 0.001) are significant indicators of antigen specific immunity. ROC curves plotted to assess the performance of tritiated thymidine incorporation and the ELISPOT assay indicate that SI is a significant indicator of low T cell response to the HER-2/neu vaccine (p = 0.05), and of moderate and robust responses to tt (p = 0.01) and CMV (p = 0.016), respectively. IFN-gamma precursor frequency is a significant indicator of a robust T cell response to CMV (p = 0.03), but not of moderate tt (p = 0.09), or low HER-2/neu (p = 0.09) T cell responses. CONCLUSION: These data underscore the importance of taking into consideration the performance characteristics of assays used to measure T cell immunity. This consideration is particularly necessary when determining which method to utilize for assessing responses to immunotherapeutic manipulations in cancer patients. PMID- 17850667 TI - Indivo: a personally controlled health record for health information exchange and communication. AB - BACKGROUND: Personally controlled health records (PCHRs), a subset of personal health records (PHRs), enable a patient to assemble, maintain and manage a secure copy of his or her medical data. Indivo (formerly PING) is an open source, open standards PCHR with an open application programming interface (API). RESULTS: We describe how the PCHR platform can provide standard building blocks for networked PHR applications. Indivo allows the ready integration of diverse sources of medical data under a patient's control through the use of standards-based communication protocols and APIs for connecting PCHRs to existing and future health information systems. CONCLUSION: The strict and transparent personal control model is designed to encourage widespread participation by patients, healthcare providers and institutions, thus creating the ecosystem for development of innovative, consumer-focused healthcare applications. PMID- 17850669 TI - Reliability of movement control tests in the lumbar spine. AB - BACKGROUND: Movement control dysfunction [MCD] reduces active control of movements. Patients with MCD might form an important subgroup among patients with non specific low back pain. The diagnosis is based on the observation of active movements. Although widely used clinically, only a few studies have been performed to determine the test reliability. The aim of this study was to determine the inter- and intra-observer reliability of movement control dysfunction tests of the lumbar spine. METHODS: We videoed patients performing a standardized test battery consisting of 10 active movement tests for motor control in 27 patients with non specific low back pain and 13 patients with other diagnoses but without back pain. Four physiotherapists independently rated test performances as correct or incorrect per observation, blinded to all other patient information and to each other. The study was conducted in a private physiotherapy outpatient practice in Reinach, Switzerland. Kappa coefficients, percentage agreements and confidence intervals for inter- and intra-rater results were calculated. RESULTS: The kappa values for inter-tester reliability ranged between 0.24 - 0.71. Six tests out of ten showed a substantial reliability [k > 0.6]. Intra-tester reliability was between 0.51 - 0.96, all tests but one showed substantial reliability [k > 0.6]. CONCLUSION: Physiotherapists were able to reliably rate most of the tests in this series of motor control tasks as being performed correctly or not, by viewing films of patients with and without back pain performing the task. PMID- 17850668 TI - A Marfan syndrome gene expression phenotype in cultured skin fibroblasts. AB - BACKGROUND: Marfan syndrome (MFS) is a heritable connective tissue disorder caused by mutations in the fibrillin-1 gene. This syndrome constitutes a significant identifiable subtype of aortic aneurysmal disease, accounting for over 5% of ascending and thoracic aortic aneurysms. RESULTS: We used spotted membrane DNA macroarrays to identify genes whose altered expression levels may contribute to the phenotype of the disease. Our analysis of 4132 genes identified a subset with significant expression differences between skin fibroblast cultures from unaffected controls versus cultures from affected individuals with known fibrillin-1 mutations. Subsequently, 10 genes were chosen for validation by quantitative RT-PCR. CONCLUSION: Differential expression of many of the validated genes was associated with MFS samples when an additional group of unaffected and MFS affected subjects were analyzed (p-value < 3 x 10-6 under the null hypothesis that expression levels in cultured fibroblasts are unaffected by MFS status). An unexpected observation was the range of individual gene expression. In unaffected control subjects, expression ranges exceeding 10 fold were seen in many of the genes selected for qRT-PCR validation. The variation in expression in the MFS affected subjects was even greater. PMID- 17850670 TI - Comparison of patient comprehension of rapid HIV pre-test fundamentals by information delivery format in an emergency department setting. AB - BACKGROUND: Two trials were conducted to compare emergency department patient comprehension of rapid HIV pre-test information using different methods to deliver this information. METHODS: Patients were enrolled for these two trials at a US emergency department between February 2005 and January 2006. In Trial One, patients were randomized to a no pre-test information or an in-person discussion arm. In Trial Two, a separate group of patients were randomized to an in-person discussion arm or a Tablet PC-based video arm. The video, "Do you know about rapid HIV testing?", and the in-person discussion contained identical Centers for Disease Control and Prevention-suggested pre-test information components as well as information on rapid HIV testing with OraQuick. Participants were compared by information arm on their comprehension of the pre-test information by their score on a 26-item questionnaire using the Wilcoxon rank-sum test. RESULTS: In Trial One, 38 patients completed the no-information arm and 31 completed the in-person discussion arm. Of these 69 patients, 63.8% had twelve years or fewer of formal education and 66.7% had previously been tested for HIV. The mean score on the questionnaire for the in-person discussion arm was higher than for the no information arm (18.7 vs. 13.3, p < or = 0.0001). In Trial Two, 59 patients completed the in-person discussion and 55 completed the video arms. Of these 114 patients, 50.9% had twelve years or fewer of formal education and 68.4% had previously been tested for HIV. The mean score on the questionnaire for the video arm was similar to the in-person discussion arm (20.0 vs. 19.2; p < or = 0.33). CONCLUSION: The video "Do you know about rapid HIV testing?" appears to be an acceptable substitute for an in-person pre-test discussion on rapid HIV testing with OraQuick. In terms of adequately informing ED patients about rapid HIV testing, either form of pre-test information is preferable than for patients to receive no pre-test information. PMID- 17850671 TI - Use of a population-based survey to determine incidence of AIDS-defining opportunistic illnesses among HIV-positive persons receiving medical care in the United States. AB - BACKGROUND: Diagnosis of an opportunistic illness (OI) in a person with HIV infection is a sentinel event, indicating opportunities for improving diagnosis of HIV infection and secondary prevention efforts. In the past, rates of OIs in the United States have been calculated in observational cohorts, which may have limited representativeness. METHODS: We used data from a 1998 population-based survey of persons in care for HIV infection to demonstrate the utility of population-based survey data for the calculation of OI rates, with inference to populations in care for HIV infection in three geographic areas: King County Washington, selected health districts in Louisiana, and the state of Michigan. RESULTS: The overall OI rate was 13.8 per 100 persons with HIV infection in care during 1998 (95% CI, 10.2-17.3). In 1998, an estimated 11.3% of all persons with HIV in care in these areas had at least one OI diagnosis (CI, 8.8-13.9). The most commonly diagnosed OIs were Pneumocystis jiroveci pneumonia (PCP) (annual incidence 2.4 per 100 persons, CI 1.0-3.8) and cytomegalovirus retinitis (annual incidence 2.4 per 100 persons, CI 1.0-3.7). OI diagnosis rates were higher in Michigan than in the other two geographic areas, and were different among patients who were white, black and of other races, but were not different by sex or history of injection drug use. CONCLUSION: Data from population-based surveys and, in the coming years, clinical outcomes surveillance systems in the United States - can be used to calculate OI rates with improved generalizability, and such rates should be used in the future as a meaningful indicator of clinical outcomes in persons with HIV infection in care. PMID- 17850672 TI - Differential regulation of iron chelator-induced IL-8 synthesis via MAP kinase and NF-kappaB in immortalized and malignant oral keratinocytes. AB - BACKGROUND: Interleukin-8 (IL-8) is a cytokine that plays an important role in tumor progression in a variety of cancer types; however, its regulation is not well understood in oral cancer cells. In the present study, we examined the expression and mechanism of IL-8 in which it is involved by treating immortalized (IHOK) and malignant human oral keratinocytes (HN12) cells with deferoxamine (DFO). METHODS: IL-8 production was measured by an enzyme-linked immunoabsorbent assay and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Electrophoretic mobility shift assays was used to determine NF-kappaB binding activity. Phosphorylation and degradation of the I-kappaB were analyized by Western blot. RESULTS: IHOK cells incubated with DFO showed increased expression of IL-8 mRNA, as well as higher release of the IL-8 protein. The up-regulation of DFO-induced IL-8 expression was higher in IHOK cells than in HN12 cells and was concentration-dependent. DFO acted additively with IL-1beta to strongly up regulate IL-8 in IHOK cells but not in HN12 cells. Accordingly, selective p38 and ERK1/2 inhibitors for both kinases abolished DFO-induced IL-8 expression in both IHOK and HN12 cells. Furthermore, DFO induced the degradation and phosphorylation of IkappaB, and activation of NF-kappaB. The IL-8 inducing effects of DFO were mediated by a nitric oxide donor (S-nitrosoglutathione), and by pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB, as well as by wortmannin, which inhibits the phosphatidylinositol 3-kinase-dependent activation of NAD(P)H oxidase. CONCLUSION: This results demonstrate that DFO-induced IL-8 acts via multiple signaling pathways in immortalized and malignant oral keratinocytes, and that the control of IL-8 may be an important target for immunotheraphy against human oral premalignant lesions. PMID- 17850673 TI - Distance to food stores & adolescent male fruit and vegetable consumption: mediation effects. AB - BACKGROUND: The physical environments in which adolescents reside and their access to food stores may influence their consumption of fruit and vegetables. This association could either be direct or mediated via psychosocial variables or home availability of fruit and vegetables. A greater understanding of these associations would aide the design of new interventions. The purpose of this study was to examine associations between distance to food stores and restaurants and fruit and vegetable consumption and the possible mediating role of psychosocial variables and home availability. METHODS: Fruit and vegetable consumption of 204 Boy Scouts was assessed by a food frequency questionnaire in 2003. Participant addresses were geo-coded and distance to different types of food stores and restaurants calculated. Fruit and vegetable preferences, home availability and self-efficacy were measured. Regression models were run with backward deletion of non-significant environmental and psychosocial variables. Mediation tests were performed. RESULTS: Residing further away from a small food store (SFS) (convenience store and drug store) was associated with increased fruit and juice and low fat vegetable consumption. Residing closer to a fast food restaurant was associated with increased high fat vegetable and fruit and juice consumption. Vegetable preferences partially mediated (26%) the relationship between low fat vegetable consumption and distance to the nearest SFS. CONCLUSION: Distance to SFS and fast food restaurants were associated with fruit and vegetable consumption among male adolescents. Vegetable preferences partially mediated the distance to low fat vegetable relationship. More research is needed to elucidate how environmental variables impact children's dietary intake. PMID- 17850674 TI - The assessment of depression awareness and help-seeking behaviour: experiences with the International Depression Literacy Survey. AB - BACKGROUND: Depression causes substantial disease burden in both developed and developing countries. To reduce this burden, we need to promote understanding of depression as a major health condition. The International Depression Literacy Survey (IDLS) has been developed to assess understanding of depression in different cultural and health care settings. METHODS: Four groups of Australian university students completed the survey: medical students in second (n = 103) and fourth (n = 82) years of a graduate course, ethnic Chinese students (n = 184) and general undergraduate students (n = 38). RESULTS: Differences between the student groups were evident, with fourth year medical students demonstrating greater general health and depression literacy than second year medical students. Australian undergraduate students demonstrated better depression literacy than those from ethnic Chinese backgrounds. Ethnicity also influenced help seeking and treatment preferences (with more Chinese students being inclined to seek help from pharmacists), beliefs about discrimination and perceptions regarding stigma. CONCLUSION: The IDLS does detect significant differences in understanding of depression among groups from different ethnic backgrounds and between those who differ in terms of prior health training. These preliminary results suggest that it may be well suited for use in a wider international context. Further investigation of the utility of the IDLS is required before these results could be extrapolated to other populations. PMID- 17850675 TI - Metabolic syndrome in a Taiwanese metropolitan adult population. AB - BACKGROUND: Metabolic syndrome (MS) is a combination of medical disorders that increase one's risk for cardiovascular disease and diabetes. Little information exists on the prevalence of MS in a general adult population in Taiwan. METHODS: We did a cross-sectional survey in a representative sample of 2,359 Chinese adults aged 40 years and over who lived in a metropolitan city, Taiwan in 2004 05. MS was defined by Adult Treatment Panel III criteria modified for Asians. RESULTS: The prevalence of MetS was 35.32% and 43.23% in men aged 40-64 years and 65 years and over, respectively, and 24.19% and 51.82% in women aged 40-64 years and 65 years and over. Older age, postmenopausal status, higher body mass index, current smoking, low education attainment, low household income, no alcohol consumption, lower level of occupation physical activity, and a family history of diabetes were associated with increased odds of MetS. CONCLUSION: MetS was present in more than 30% of the Taiwan adult population aged 40 years and over in a metropolitan area; there were substantial variations by age and body mass index groups. PMID- 17850676 TI - My worries are no longer behind me. PMID- 17850677 TI - Tumour necrosis factor blockade and the risk of osteoporosis: back to the future. AB - Osteoporosis is a common clinical problem, especially in patients with rheumatoid arthritis (RA). A reduction in bone mineral density (BMD) of the axial and appendicular skeleton ranging from 7% to 15% has been reported in RA in studies employing a variety of densitometric techniques. Reports consistent with a beneficial effect of tumour necrosis factor blockade on BMD have begun to emerge in recent years, and in Arthritis Research and Therapy, a case control study reports that patients treated with infliximab for RA had preservation of BMD in the lumbar spine and femoral neck compared to those treated with methotrexate. PMID- 17850678 TI - Factor VII and the brain: time to get this research done! AB - Traumatic brain injury is the leading killer after trauma, in part because of coagulopathy. Factor VIIa may be a useful therapy in this setting, depending on the relative risk for thromboembolic complications. Kluger and coworkers recently conducted a retrospective review of patients with traumatic brain injury from a previous factor VIIa and trauma trial. It documents an encouragingly low rate of complications, and should provide a strong incentive to conduct a prospective study of factor VIIa in patients with severe traumatic brain injury. PMID- 17850679 TI - Measuring sleep in critically ill patients: beware the pitfalls. AB - Survivors of critical illness frequently report poor sleep while in the intensive care unit (ICU), and sleep deprivation has been hypothesized to lead to emotional distress, ICU delirium and neurocognitive dysfunction, prolongation of mechanical ventilation, and decreased immune function. Thus, the careful study of sleep in the ICU is essential to understanding possible relationships with adverse clinical outcomes. Such research, however, must be conducted using sleep measurement techniques that have important limitations in this unique setting. Polysomnography (PSG) is considered the gold standard but is cumbersome, time consuming, and expensive. As such, alternative methods of sleep measurement such as actigraphy, processed electroencephalography monitors, and subjective observation are often used. Though helpful in some instances, data obtained using these methods can often be inaccurate and misleading. Even PSG itself must be interpreted with caution in this population due to effects of critical illness and associated treatments. PMID- 17850680 TI - Is there more to glycaemic control than meets the eye? AB - Tight glycaemic control has emerged as a major focus in critical care. However, the struggle to repeat, improve and standardize the results of the initial landmark studies is ongoing. The prospective computerized glycaemic control study by Shulman et al. highlights two emerging and often overlooked aspects of intensive insulin therapy protocols beyond simple glycaemic performance. First, the clinical ergonomics and ability to integrate into the critical care unit workflow must be considered as they may impact results and definitely affect uptake. Second, the real lessons of any protocol's performance are likely to be best realized by comparison with other results, a task that is very difficult without a consensus method of reporting that allows such comparisons across studies. Embracing these issues will take the field closer to accepted, repeatable approaches to tight glycaemic control. PMID- 17850681 TI - Number needed to treat = six: therapeutic hypothermia following cardiac arrest- an effective and cheap approach to save lives. AB - In 2005, the European Resuscitation Council (ERC) guidelines stated: Unconscious adult patients with spontaneous circulation after out-of-hospital ventricular fibrillation cardiac arrest should be cooled to 32 to 34 degrees C for 12 to 24 hours. Patients with cardiac arrest from a non-shockable rhythm, in-hospital patients and children may also benefit from hypothermia. There is no argument to wait. We have to treat the next unconscious cardiac arrest patient with hypothermia. PMID- 17850682 TI - Dextran-70 to modulate inflammatory response after cardiopulmonary bypass: potential for a novel approach? AB - Potential deleterious effects of cardiopulmonary bypass (CPB) and cardioplegic cardiac arrest are known to influence outcome. The inflammatory response after CPB may have unfavourable effects especially in high-risk patients, for example, the very elderly. Thus, to blunt the release of pro-inflammatory mediators seems to be a promising approach. So far, numerous attempts at immune modulation have been performed. However, the management of cardiac surgery patients needs further improvement. In this context, Gombocz and colleagues investigated the potential anti-inflammatory effect of dextran-70. Their results suggest that compared to gelatine, dextran-70 reduces the inflammatory response in patients after CPB. PMID- 17850684 TI - Different small-dose remifentanil blunting the cardiovascular response to laryngoscopy and intubation in children: a randomized double-blind comparison. AB - BACKGROUND: The available data provide inconsistent results on the efficacy of small-dose remifentanil attenuating the cardiovascular response to intubation in children. Therefore, this randomized double-blind study was designed to assess the ability of different small doses of remifentanil on the cardiovascular intubation response in children, with the aim of determining the optimal dose of remifentanil for this purpose. METHODS: One hundred and twenty-four children aged 3-9 yr were randomized to one of four groups to receive the following in a double blind manner: normal saline (Group 1), remifentanil 0.75 microg kg(-1) (Group 2), remifentanil 1 microg kg(-1) (Group 3) and remifentanil 1.25 microg kg(-1) (Group 4). Non-invasive blood pressure and heart rate were recorded before anaesthesia induction (baseline value), immediately before intubation (postinduction values), at intubation and at 1 min intervals for 5 min after intubation. RESULTS: Tracheal intubation caused significant increases in systolic blood pressure and heart rate in Groups 1-3 compared with the baseline values. The maximum percent increases of systolic blood pressure and heart rate were 10% and 26% of the baseline values, respectively, in Group 2; 5% and 14% in Group 3; and 1% and 8% in Group 4 compared with 27% and 37% in Group 1. Except for the Group 3 vs. Group 4 comparison, there were significant differences among the four groups in the maximum percent increases of systolic blood pressure and heart rate. CONCLUSIONS: When used as part of anaesthesia induction with propofol and vecuronium in children, bolus administration of remifentanil resulted in a dose-related attenuation of the cardiovascular intubation response. PMID- 17850685 TI - Cardiac output measurements with electrical velocimetry in patients undergoing CABG surgery: a comparison with intermittent thermodilution. AB - BACKGROUND AND OBJECTIVE: The purpose was to study the agreement between cardiac output measurements with electrical velocimetry vs. intermittent thermodilution before and after coronary artery bypass graft surgery. METHODS: Cardiac output was measured simultaneously with electrical velocimetry and intermittent thermodilution before and immediately after coronary artery bypass graft surgery, and in the intensive care unit. Measurements were performed in three different body positions. The results were analysed according to Bland and Altman. RESULTS: The mean bias of all 150 paired measurements in 16 patients was 0.21 +/- 0.78 L min(-1), and the mean error was 40%. Before skin incision the mean bias was 0.04 +/- 0.41 L min(-1), and the mean error was 25%. After skin closure the mean bias was 0.57 +/- 0.92 L min(-1), and the mean error was 42%. In the intensive care unit the mean bias was 0.26 +/- 0.68 L min(-1), and the mean error was 32%. CONCLUSIONS: The agreement between cardiac output measurements with electrical velocimetry and intermittent thermodilution was clinically acceptable only before skin incision in coronary artery bypass graft surgery. The mean error was unacceptably high immediately after skin closure and was at a borderline level in the intensive care unit. Thus, the overall accuracy of cardiac output measurements with the electrical velocimetry technique during coronary artery bypass graft surgery is not clinically unacceptable. PMID- 17850686 TI - Vertigo, dizziness and imbalance in the elderly. AB - OBJECTIVE: The aim of this retrospective analysis was to evaluate the diagnosis of vertigo, dizziness and imbalance in elderly patients in two tertiary neurotology clinics. DESIGN AND SETTING: Six hundred and seventy-seven patients aged over 65 years were assessed by the same senior author, and 601 patients were enrolled in the study. RESULTS: The most frequent diagnoses were benign paroxysmal positional vertigo (42.43 per cent), idiopathic vestibulopathy (20.29 per cent), migraine vestibulopathy (13.15 per cent), Meniere's disease (12.47 per cent) and acute vestibular attack (6.49 per cent). CONCLUSION AND SIGNIFICANCE: This retrospective study showed that 93.5 per cent of the elderly patients studied had been diagnosed with peripheral vertigo. The majority of patients had been classified as having benign paroxysmal positional vertigo, idiopathic vestibulopathy or migraine vestibulopathy. PMID- 17850687 TI - Abortion index and mortality of offspring among women of different age, caste and population groups of north Indian Muslims. AB - The Muslims of Aligarh city are predominantly Sunnis, although there are also a considerable number of Shias. Among the Sunnis, approximately a quarter belong to Syed, Sheikh, Moghal and Pathan groups, and three-quarters belong to various lower biradaris. In the present study, 304 women attending the Primary Health Centre of the J. N. Medical College and Hospital, Aligarh Muslim University, Uttar Pradesh, were surveyed and the following recorded among Muslim women of high-rank (Ashraf) and low-rank (Ajlaf) castes: incidence of marriage, age of the mother at the time of marriage, present age of the mother, abortions, still births, pre-reproductive mortality and overall mortality. The Ashraf are comprised of the Sheikh, Syed and Pathan, whereas the Ajlafs have Qureshi, Saifi and Ansari biradaris. Maternal age was scored as above and below 45 years in each biradari. Significant effects of maternal age were seen on mortality of offspring, whereas populations did not show consistent differences, except when Ashrafs and Ajlafs were considered separately. The results show higher mortality and abortions for various groups. This may be due to various biological and socio cultural factors, including hidden inbreeding in the remote past. PMID- 17850688 TI - Rapid fertility decline in Iran: analysis of intermediate variables. AB - The remarkable decline in fertility in Iran, which saw the total fertility rate fall from 7 children per woman in 1986 to 2 in 2000, has received only limited analysis in the demographic literature. Using the 2000 Iran Demographic and Health Survey and Bongaarts' age-specific fertility model, this paper examines the role of the major proximate determinants of fertility in bringing about the rapid decrease in fertility in Iran. The analysis indicates that contraception had the largest effect on fertility, accounting for 61% of the reduction in fertility from its theoretical maximum. The fertility-inhibiting effect of marriage patterns accounted for an additional 31% reduction, and was most important among the young. Further analysis of contraceptive behaviour suggests that the current period fertility rate of 2.0 children per woman is an outcome of a synchronization of delaying and spacing of births among younger women with stopping of childbearing among women in the middle and late reproductive ages. The policy implications of the results are discussed. PMID- 17850683 TI - Cells of the synovium in rheumatoid arthritis. Dendritic cells. AB - Dendritic cells are the major antigen-presenting and antigen-priming cells of the immune system. We review the antigen-presenting and proinflammatory roles played by dendritic cells in the initiation of rheumatoid arthritis (RA) and atherosclerosis, which complicates RA. Various signals that promote the activation of NF-kappaB and the secretion of TNF and IL-1 drive the maturation of dendritic cells to prime self-specific responses, and drive the perpetuation of synovial inflammation. These signals may include genetic factors, infection, cigarette smoking, immunostimulatory DNA and oxidized low-density lipoprotein, with major involvement of autoantibodies. We propose that the pathogenesis of RA and atherosclerosis is intimately linked, with the vascular disease of RA driven by similar and simultaneous triggers to NF-kappaB. PMID- 17850689 TI - Modelling control measures to reduce the impact of pandemic influenza among schoolchildren. AB - We coupled the Wells-Riley equation and the susceptible-exposed-infected-recovery (SEIR) model to quantify the impact of the combination of indoor air-based control measures of enhanced ventilation and respiratory masking in containing pandemic influenza within an elementary school. We integrated indoor environmental factors of a real elementary school and aetiological characteristics of influenza to estimate the age-specific risk of infection (P) and basic reproduction number (R(0)). We combined the enhanced ventilation rates of 0.5, 1, 1.5, and 2/h and respiratory masking with 60%, 70%, 80%, and 95% efficacies, respectively, to predict the reducing level of R0. We also took into account the critical vaccination coverage rate among schoolchildren. Age-specific P and R(0) were estimated respectively to be 0.29 and 16.90; 0.56 and 16.11; 0.59 and 12.88; 0.64 and 16.09; and 0.07 and 2.80 for five age groups 4-6, 7-8, 9-10, 11-12, and 25-45 years, indicating pre-schoolchildren have the highest transmission potential. We conclude that our integrated approach, employing the mechanism of transmission of indoor respiratory infection, population-dynamic transmission model, and the impact of infectious control programmes, is a powerful tool for risk profiling prediction of pandemic influenza among schoolchildren. PMID- 17850691 TI - ? PMID- 17850690 TI - Epidemiological features of Mediterranean spotted fever, murine typhus, and Q fever in Split-Dalmatia County (Croatia), 1982-2002. AB - We determined the epidemiological features of three zoonoses in hospitalized patients in southern Croatia. Patients were diagnosed by serological testing. Clinical and epidemiological data were also collected. Between 1982 and 2002, Mediterranean spotted fever (MSF) was diagnosed in 126 (incidence rate 1.27/100,000 per year), murine typhus (MT), in 57 (incidence rate 0.57/100,000 per year), and Q fever in 170 (incidence rate 1.7/100,000 per year) patients. MSF and Q fever were characterized by a marked seasonality. Incidences of Q fever and of MSF were higher for males than for females (P<0.0001 and P=0.0024, respectively). The most frequent of the three zoonoses in children was MSF. Q fever and MT cases were mostly seen in the 21-50 years age group. We found no statistically significant differences between season- and gender-specific incidence rates of MT. Whereas infections due to rickettsiae decreased, the incidence of Q fever increased over the last 12 years of the study. PMID- 17850692 TI - [Distribution of hepatitis B virus genotypes in patients with chronic hepatitis B virus infection among 12 cities in China]. AB - OBJECTIVE: To investigate the distribution of hepatitis B virus (HBV) genotypes in patients with chronic HBV infection among 11 cities of China. METHODS: A total of 1214 serum samples from patients with chronic HBV infection were collected in 11 cities of China, including Beijing, Qingyuan, Shenzhen, Shijiazhuang, Hanchuan, Nanjing, Changchun, Liaocheng, Jinan, Ningbo and Wenzhou. Genotypes of the 1214 HBV strains were identified by PCR method with type specific primers. Parts of the results were confirmed by direct sequencing analysis of PCR products. RESULTS: Among the 1214 patients with chronic HBV infection, 0.7% (9/1214)were genotype A, 28.4% (345/1214)genotype B, 58.4% (709/1214) genotype C, and 12.4% (151/1214) genotype B and genotype C mixed infection. No other genotypes were found. Genotype C was predominant in the northern part of China, such as Changchun, Beijing, Shijiazhuang,while genotype B was more commonly seen in south of China. 71.4% (20/28) for patients from Qingyuan and 63.6% (70/110) from Shenzhen were infected with genotype B. CONCLUSION: HBV genotypes had distinct geographic distribution. Genotype B and C the predominant strains in patients with chronic HBV infection in China. Genotype C was predominantly identified in the northern part of China versus genotype B the south. PMID- 17850693 TI - [Studies on the status of immune memory after completion of hepatitis B vaccination]. AB - OBJECTIVE: To study the immune memory in vaccinees after the completion of a full schedule hepatitis B immunization. METHODS: One thousand and two hundred one infants born in 1987 -1989 were immunized with 3 doses of plasma derived hepatitis B vaccine, while 2484 newborn babies during 1996-1999 were injected with 3 doses of the yeast recombinant hepatitis B vaccine. All of the infants under observation were tested for HBsAg, anti-HBs and anti-HBc, in 2005. Of 959 individuals negative for anti-HBs (< 10 mIU/ml), HBsAg and anti-HBc, 228 were immunized with plasma-derived vaccine and 731 with yeast recombinant vaccine after birth. All of them were detected for anti-HBs 15 days after a booster of 10 Ipg yeast recombinant vaccine. In addition, interleukin-2 (IL-2) was detected in 11 non-responders and 22 responders after boostering, using an enzyme-linked immunospot (ELISPOT). The anti-HBs levels of 190 individuals (91 with plasma derived vaccine and 99 with yeast recombinant vaccine) who had had quantitative data on their antibody status after the primary hepatitis B vaccination, were compared with that after the boostering. RESULTS: Among the individuals who received plasma derived vaccine 16-18 years ago, 79.82% of them showed the signs of immune memory after one booster, with a geometric mean titer (GMT)of 325.69 mIU/ml. Of the individuals who received the yeast recombinant vaccine 6-9 years ago, 95.62% showed immune memory after one booster,with its GMT of 745.18 mIU/ml. Anti-HBs levels induced by the booster were associated with that after the primary immunization. The positive rate of IL-2 was 40.91% in subjects with good immune memory. However, IL-2 was not detected in non-responders after the booster (P < 0.01). CONCLUSION: Most of the individuals who had received a completed schedule of primary hepatitis B vaccination and seroconverted from anti-HBs positive to negative,showed the signs of having immune memory after the booster. Only a small proportion of the vaccinees had lost their immune memory during the long term follow-up period, suggesting that these individuals should receive a booster of hepatitis B vaccine in the highly endemic areas of hepatitis B. Hepatitis B virus; Immune memory; Booster immunization PMID- 17850694 TI - [Study on the efficacy of hepatitis B virus vaccination and its influencing factors among children in rural area of Jiangsu province]. AB - OBJECTIVE: To evaluate the efficacy of hepatitis B viruse (HBV) vaccination and its influencing factors among children in rural area of Jiangsu province. METHODS: Twenty-five hundred and twenty-two children born after 1998 in rural area were selected as the study population using multistage cluster sampling method. HBsAg and anti-HBs were detected by enzyme linked immunoassay (ELISA) and radio-immunoassay (RIA), respectively. Anti-HBs negative children were boosted using different hepatitis B vaccines and the efficacy was compared. Factors causing HBV infection in HBsAg positive children were also investigated. RESULTS: HBsAg positive rates in 1-7 year olds were 0.28%-1.28%, and the anti-HBs positive rates decreased from 76.7% to 45.5%. The HBsAg positive rate in children not timely vaccinated was significantly higher than those with HBV vaccine injection within 24 hours after birth (1.4% vs. 0.5%, P = 0.031). More than 90% of the anti HBs negative children had protective level of anti-HBs after boosted with HBV vaccine. CONCLUSION: HBsAg positive rate in children born after 1998 in rural area of Jiangsu province decreased significantly, with an average of 0.8%. The reason for HBsAg carriage in children might be attributed to mother-to-infant transmission or not timely HBV vaccination. PMID- 17850696 TI - ? PMID- 17850695 TI - [Study on the kinesis of cellular immunity in adults vaccinated with recombinant hepatitis B vaccine]. AB - OBJECTIVE: To evaluate the kinesis of cellular immunity in adults who were vaccinated with yeast recombinant hepatitis B(rHB) vaccine and the correlation between cellular and humoral immune responses induced by the vaccine. METHODS: Eight adults were vaccinated with rHB vaccine according to 0, 1,2 month schedule. The peripheral blood mononuclear cells(PBMCs) were collected at the 3, 8, 21, 34 and 65 days after the first dose. The high purity of CD4+ and CD8+ T cells obtained by sorting from PBMCs were restimulated with recombinant hepatitis B surface antigens (rHBsAg) or peptides. The spot forming cell (SFC) of IFN-gamma, IL-2 and IL-4 of CD4+ and CD8+ T cells were detected by enzyme-linked immunospot (ELISPOT). RESULTS: The characteristics of IFN-gamma, IL-2 and IL-4 of CD4+ and CD8+ T cells appeared different after immunization with rHB vaccine. IFN-gamma of CD8+ and CD4+ T cells could be detected early with stable SFC, while the IL-2 and IL-4 of CD4+ T cells appeared late but increased after the second and third dose of vaccination. The positive rate of IL-4 of CD4+ T cells were significantly correlated with the positive rate of anti-HBs, while the SFCs of IL-4 and IL-2 of CD4+ T cells were also significantly related to the titers of anti-FIBs. CONCLUSION: IFN-gamma could be detected early after rHB vaccination in adults, and the positive rates of IL-4 and IL-2 were correlated with that of anti-HBs. PMID- 17850697 TI - [Interruption failure of heptitis B virus vaccination in mother-to-infant transmission and heptitis B virus genotypes and preC/BCP mutations]. AB - OBJECTIVE: To investigate the association of heptitis B virus (HBV) genotypes and precore(PreC)/basal core promoter(BCP) mutation with interruption failure of HBV vaccination in mother-to-infant transmission. METHODS: A total number of 208 serum samples were collected from infants and mothers,including 16 infants who had become HBsAg-positive despite a complete and timely course of immunization and another 88 infants successfully protected from mother-to infant HBV transmission. HBV genotypes were determined by type-specific primers PCR method. PreC/BCP mutations were detected by direct sequencing of PCR products, and Clustal W 1.8 software was applied to analyzing the sequences. RESULTS: Of 16 mothers who were having vaccine failure infants, 15 (93.8%) were HBeAg positive and infected with genotype C (15/15, 100%). Among 88 mothers of having children being protected by vaccine, 51 (58.0%) were HBeAg positive, with 45.1% (23/51) of genotype C. The proportion of genotype C in HBeAg mothers of infants with vaccine failure, was significantly higher than that of mothers with vaccine protected infants (chi2 = 14.3, P = 0.003). However, the frequencies of T1762/A1764 mutations had no significant differences between genotype C HBeAg positive mothers with vaccine failure or protected infants (33.3% and 13.3%, respectively, P = 0.4). No A1896 mutation was found in these two groups. CONCLUSION: HBV genotype C might contribute to the immune failure of HBV vaccination in mother-to infant transmission, while PreC/BCP mutation might not have correlation with it. PMID- 17850698 TI - [Role of mutations on the "hepatitis B virus 'a' determinant hotpoint" to the efficacy of hepatitis B vaccine]. AB - OBJECTIVE: To study how hepatitis B virus(HBV) 'a' determinant hotpoint mutations were influecing the hepatitis B vaccine efficacy. METHODS: Primers were designed in HBV conservative region, and the degenerate probes for detecting 16 'a' determinant hotpoint mutations were developed for gene chips. Sensitivity and specificity of the gene chips were evaluated by clone sequencing. Sera of 47 pairs of mothers and infants with immune failure and 323 mothers of children with immune protection of HB vaccine were detected by the gene chips. RESULTS: Result from clone sequencing demonstrated that the gene chips were specific for the detection of 'a' determinant hotpoint mutations. The wild type of HBV was still dominant, with the prevalence of 78.66%, and the mutation frequencies of 126A, 145R, 126S-1, 126S-2, 129H, 144A, and 129R were 11.27%, 5.76%, 5.28%, 4.56%, 1.20%, 0.72% and 0.24%, respectively. The prevalence of 126A mutation was significantly higher than that of other mutations(P < 0.01). No significant differences were found in mother-infant transmission rates of 126A, 126S-1, 126S 2 and 145R variants. CONCLUSION: The currently available hepatitis B vaccine could block mother-infant transmission of 126A, 126S and 145R variants. It appears that there is no need to develop a new hepatitis B vaccine against 126 and 145 variants at present, but the consistent epidemiological surveillance on HBV mutants should be carried out. PMID- 17850699 TI - [Study on the antiviral therapy program among people with human immunodeficiency virus in Guangxi Zhuang Authority]. AB - OBJECTIVE: To explore the reconstitution of immune function and viral suppression condition and to analyze the occurrence of drug resistance HIV-1 variants and its prevalence after using HAART in Guangxi Autonomy Region. METHODS: From July 2004 to October 2005, 133 HIV infected individuals who had received HAART for more than three months were recruited, and 58 infected persons with no antiviral therapy were selected as controls. Questionnaire was used to collect information about the adherence of HAART therapy. Immune reconstruction and viral suppress conditions were obtained by CD4+ counts and viral load and RT-PCR were used to amplify the PR and RT regions of HIV-1 genome while HIV-1 drug resistance rates were analyzed to show the occurrence and prevalence in both treated and naive patients. RESULTS: In terms of CD4+ T cell counts: 70.69% of the treated patients showed obvious increase and 23.28% had no apparent change but 6.03% of them went down. 70.48% of the patients who had received antiviral therapy more than 3 months had their viral load lower than the low detectable limitation. When comparing the log of viral load between treated and untreated cohort, the mean value of the treated was obviously less than the untreated (P < 0.05). However,the result of drug resistance showed no obvious difference between the treated and untreated groups. CONCLUSION: The antiviral therapy being used in Guangxi region, had achieved obvious effect on the reconstruction of immune system and the suppression of viral replication in vivo under good adherence while the occurrence of drug-resistant HIV strain did not show obvious difference between treated and naive patient groups. PMID- 17850700 TI - [A three-year follow-up study on sera specific antibody in severe acute respiratory syndrome cases after the onset of illness]. AB - OBJECTIVE: To study the variation of specific antibody among convalescent of severe acute respiratory syndrome (SARS) patients through a three-year program. METHODS: Sera samples were collected from SARS cases in the 5th, 20th and 35th month after onset of the illness. The SARS-CoV specific antibody was detected for all of them by ELISA and neutralized test simultaneously. The titer of neutralizing antibodies was calculated using Reed-Muench method, and the comparison between different time groups was analyzed regarding the variance of data on repeated measures after logarithm conversion. RESULTS: 13, 17 and 13 sera samples were collected in the 5th, 20th and 35th month after onset. Results showed that despite the fact that the positive rates of ELISA antibody were 100%, 82.4% and 84.6% respectively,the neutralizing antibody was still positive for all the samples. The average neutralizing antibody titers were 1:43 (1:16-1:203), 1:36 (1:17-1:59) and 1:21 (1:10-1:39) on the 5th, 20th and 35th month after onset, and the differences were statistically significant (F = 60.419, P < 0.001). On the 35th month after the onset, 30.8% (4/13) of the patients were still having the neutralizing antibody level of above 1:36, but the neutralizing antibody level in another 30.8% (4/13) of the patients had decreased to as low as 1:10, when the cut-off level was set as 1:8. CONCLUSION: Results of the study indicated that the neutralizing antibody of SARS cases could last for at least three years, but the sera specific antibody in SARS cases decreased gradually when time went by. However, neutralizing antibody in some of the cases decreased to a lower level on the 35th month. Further follow-up study was worthwhile to observe the long-lasting profile of antibody existence on SARS cases. PMID- 17850701 TI - [Study on the molecular typing and epidemiology of non-polio enteroviruses isolated from Yunnan province, China]. AB - OBJECTIVE: This report presented an overview on the epidemiology of enterovirus in Yunnan province, the People's Republic of China. METHODS: A total of 210 strains of non-polioviruses isolated under acute flaccid paralysis surveillance during a 5-year study period from 1997 to 2000 and 2004 were examined. Of the 210 non-polioviruses strains, a total of 12 strains of adenoviruses were serologically identified. The remaining 198 isolates were used for molecular typing, and the viral genomes of 195 nonpolio enteroviruses (NPEVs) were translated to corresponding amino acid sequences and compared with those of the prototype strains. RESULTS: Based on molecular typing, 5 isolates were classified into 5 serotypes of human enterovirus A species while 158 isolates into 34 serotypes of B and 32 isolates into 6 serotypes of C species. However, we did not isolate any viruses which belonged to human enterovirus D species. Thus, under acute flaccid paralysis surveillance, human enterovirus B species accounted for 75.2% of the 210 isolates and was considered as the predominant one, followed by human enterovirus C (12.2%), adenovirus (5.7%), and human enterovirus A (2.4%). CONCLUSION: Although the epidemiological characteristics of NPEVs from Yunnan province remained "unknown", the molecular typing method had provided us a breakthrough to understand the epidemiology of these viruses. PMID- 17850702 TI - [Correlates of and willingness to participate in HIV voluntary counseling and testing among migrants in a city of Shanxi province]. AB - OBJECTIVE: To determine the correlates of and willingness to participate(WTP) in HIV voluntary counseling and testing (VCT) among migrants in Shanxi province. METHODS: Through quota sampling, a total of 1280 migrants were recruited from 6 different venues where migrants were most likely employed to administer a face-to face anonymous interview. RESULTS: Knowledge of VCT among migrants was low. Only 56.6% of migrants had heard of HIV voluntary counseling and testing. 64.5% reported willingness to accept VCT after participants were informed that HIV counseling and testing was offered free of charge Centers for Disease Prevention and Control (48.7%), hospital (27.0%) and home (18.5%) were most preferred places for VCT service. Logistic regression analysis indicated that the willingness was associated with having a history of HIV test, having better knowledge of HIV, no discrimination against people with HIV, and high HIV/AIDS perception. CONCLUSION: Community-based health education programs for improving HIV/AIDS knowledge, promoting acceptance of VCT and eliminating discrimination to HIV-infected persons were called for. PMID- 17850703 TI - [Study on the relations between concentration of endotoxin in dwelling and atopic asthma in school-age children]. AB - OBJECTIVE: To explore the effect of endotoxin concentration in dwellings on the prevalence of atopic asthma in children. METHODS: Standardized questionnaires of asthma were distributed to the parents of 2986 school children aged between 8 and 12 years and endotoxin content in children's mattress was measured by a kinetic limulus assay. A radioallergosorbent technique--fluorescence enzyme immunoassay (RAST-FEIA) was used to measure the level of specific IgE in serum. RESULTS: Complete data was available for 904 children with males more than females. There were both negative associations seen between endotoxin levels and both atopic asthma (OR = 0.48, 95% CI: 0.32-0.72, P < 0.05) and atopic sensitization (OR = 0.65, 95% CI: 0.49-0.94, P < 0.05) but not with non-atopic asthma and wheeze. Comparing with normal people, patients with atopic sensitization, atopic wheeze and atopic asthma had a higher levels of endotoxin (M-W U: 15 138.0, P < 0.01, M W U: 4858.0, P < 0.01, M-W U: 4041.0, P < 0.01). CONCLUSION: Exposure to endotoxin in early lives of children might have a protective effect on atopic asthma and sensitization. PMID- 17850704 TI - ? PMID- 17850706 TI - ? PMID- 17850705 TI - [An epidemiological study on carotid atherosclerosis among veterans in Beijing]. AB - OBJECTIVE: To investigate the prevalence and risk factors of carotid atherosclerosis (CAS) among veterans in Beijing. METHODS: 820 individuals, aged 60 or above, were randomly selected out from 8202 individuals, 21 military cadre retirement centers in Beijing. Each individual answered a questionnaire and received Doppler ultrasonic examination for an observation of the Internal-Media Thickness and structure of the carotid. A logistic regression analysis was also made to identify possible risk factors and their powers on the prevalence of CAS. RESULTS: The prevalence of carotid atherosclerosis by ultrasonic examinations among the veterans in Beijing was 44.0%, of which males taked 53.8% and females taked 33.5%. The prevalence rised with the increase of age. Among them, the prevalence ratio of CAS for ages of 60-69, 70-79, and 80 or above were 30.4%, 51.8%, 65.27%, respectively. Logistic regression was done to provide the following results: CAS risk factors include the age, sex, obesity, smoking, hypertention and diabetes mellitus. CONCLUSION: The prevalence of CAS among the veterans in Beijing rises with the increase of age. CAS risk factors include age, sex, obesity, smoking, hypertention and diabetes mellitus. PMID- 17850707 TI - [Study on the determinants of 'signing agreements' to establish smoke-free homes among 2019 parents of the secondary school students]. AB - OBJECTIVE: To explore the determinants of 'signing a agreement for establishing smoke-free homes' among the parents of secondary school students. METHODS: 2019 parents were surveyed with self-administered questionnaires on their socio demographic characteristics, smoking behaviors, attitude toward tobacco control at home and related data of their children. At the same time, parents were asked to sign an agreement for making the 'home as smoking-free'. 'Parents signing the agreement' was defined as dependent variable (0=no, 1=yes), and parent's age, gender, educational level, etc. were defined as independent ones. Multi-variant logistic regression analysis was conducted for identifying the determinants of the parents to sign an agreement for establishing 'smoking-free homes'. RESULTS: Of the 2019 surveyed parents, 1047 (51.86%) had signed the agreement including 49.25% of the fathers and 55.73% of the mothers. The results from multi-variant logistic regression analysis indicated that father's 'signing action' was significantly associated with (a) their intention of carrying out the agreements (OR = 3.37), (b) to teach their children about the consequence between smoking and health (OR = 2.10), (c) knowing tobacco control program at school (OR = 1.38), (d) reading tobacco control material provided by school (OR = 1.38), (e) being current smoker (OR = 0.53) compare to that the mother's 'signing action' was significantly associated to (a) intention to carrying out agreements (OR = 2.36), (b) teaching children not to smoke (OR = 2.22), (c) reading tobacco control material provided by school (OR = 1.57). CONCLUSION: Changing parental cognition and attitude toward smoking was beneficial to promote parental participation in tobacco control campaign and to establish 'smoking-free homes'. PMID- 17850708 TI - [Surveillance on the dynamics of leptospirosis epidemics in the Chongqing Section of the Three Gorges dam area]. AB - OBJECTIVE: To analyze the changes of leptospirosis epidemic characteristics before and after the Phase 2 'reservoir store water project' in Chongqing section of the Three Gorges dam area and to provide prevention, control and intervention measures to prevent the spread of leptospirosis from infectious focus to the Three Gorges dam area and downstream region of Changjiang River. METHODS: Changshou district and Fengdu county were selected as surveillance sites. We monitored the source of infection through examining the serum antibody of patients, healthy groups together with farm cattle measured by micro agglutination test (MAT). RESULT: Sporadic cases were reported before and after the storage of water in the reservoir. There was no significant difference found between mouse density before and after the Phase 2 reservoir project (chi2 = 1.00, P > 0.05). The main species of rat were Sewer rat before and Insectivorea after the storage of water. The germ-carrying rate of rats was 1.72% (10/583) and positive carrying rate of rats was 16.51% (18/109) when using PCR. Results showed a significant difference when comparing it to culture method (chi2 = 51.80, P < 0.01). Positive rate of leoptopirosis appeared in the serum of patients was 73.33% (33/45) with the major serum group as the Australia group. The rate of infection among the healthy group was 26.84% (233/868). There was significant difference seen between the serum antibody positive rate of epidemic prophase (23.85%) and epidemic anaphase (29.86%) of the healthy group (chi2 = 3.99, P < 0.05). The GMRT of ox serum antibody of leoptopirosis was 29.97 with Bailen group as the predominant microbial population. CONCLUSION: There was no epidemics of leptopirosis occurred in the Three Gorges dam area. There was no significant difference between mouse density before and after the storage of water in the reservoir. However, the major species of rats had a change. The natural infection level of people living in the dam area was low, but there existed potential of leoptopirosis outbreak. PMID- 17850709 TI - [Analysis on the status of Shigella spp antimicrobial resistance through data from the National Shigellosis Surveillance System in China, in 2005]. AB - OBJECTIVE: The Ministry of Public Health released the National Surveillance project on Shigellosis in August, 2005. This study was to reveal the antimicrobial resistance status of Shigella isolates through the National Shigellosis Surveillance System in 2005 in China, so as to provide evidence for the development of surveillance, prevention and cure of Shigellosis. METHODS: All the lab assistants received training from Chinese Center for Disease Control and Prevention. The project prescribed the uniform experimentation, quality control method, reagent, etc. Disc diffusion test(K-B) was carried out, following the CLSI methods. Data were analyzed by WHONET 5.4 software. RESULTS: (1) 3 serotypes were identified and S. flexneri was common that accounted for 75.5% of all Shigella isolates followed by 24.4% of S. sonnei, but only 1 strain of S. dysenteriae was separated. (2) The resistant rates to tetracycline and ampicillin in Shigella spp were quite high, as over 90.0%. However, the resistant rate to Cefotaxime was the lowest, only 6.1%. The resistant rates were different between serotypes with the resistant rates of S. flexneri to ampicillin, ampicillin/clavulanate and ciprofloxacin were higher than those of S. sonnei (P < 0.001). (3) The multiple-antibiotic-resistance status in Shigella spp was quite serious and the resistant rate to five and more antimicrobials was 54.9%. The most common resistant patterns were seen on ampicillin, nalidixin, tetracycline and sulfamethoxazole. (4) There were some differences in subtypes and antimicrobial resistance among different provinces. CONCLUSION: Cefotaxime seemed the best in curing Shigellosis at the clinic level. Programs regarding monitoring subtypes and antimicrobial resistance of Shigella should be in a continuous manner so as to understand the pathogens timely and to control the disease pertinently. PMID- 17850710 TI - ? PMID- 17850711 TI - [Analysis on the epidemiologic characteristics of human rabies in all the 31 provinces in China, from 1991 to 2005]. AB - OBJECTIVE: To study the epidemic intensity and trend of human rabies from 1991 to 2005 among 31 provinces, metropoli and municipalities in China so as to increase the awareness of the disease. METHODS: Contrastive analyses were performed and the annual publishing data by the Chinese Center for Disease Control and Prevention were used. RESULTS: The total number of reported cases was 14 942 from 1991 to 2005 with an annual average mortality rate as 0.080/100000. The increase of five-years mortality ratio on relative ratio with circular base of mortality rate were--66.24% (1996-2000 to 1991-1995) and 506.13% (2001-2005 to 1996-2000). When comparing incidence rates between 2000-2005 and 1991-1995, the relative ratio with fixed base increase became 104.62%. CONCLUSION: Among the 31 provinces, metropolis and municipalities, 27 had reported human rabies cases. The enzootic areas mainly distributed in the drainage area along the Yangtze River. The incidence rates of Guangxi, Hunan, Guizhou, Jiangxi and Guangdong were the highest. PMID- 17850712 TI - [Multi-PCR identification and virulence genes detection of Campylobacter jejuni isolated from China]. AB - OBJECTIVE: This study was to simultaneously identify Campylobacter jejuni and Campylobacter coli isolates in China by Multi-PCR assay and to study the prevalence of six virulence and toxin genes on them. METHODS: A multi-PCR method with three sets of primers specifically designed for application of a 16S rRNA as a universal control, mapA, ceuE based on the specific sequence of C. jejuni and C. coli, was applied to detect 65 Campylobacter isolates from China. Another two separately PCR Primers were directed towards the hippuricase gene (hipO) characteristic of C.jejuni and glyA gene characteristic of C. coli were performed for further confirmation. The presence of the cadF, virB11, flaA, cdtA, cdtB, cdtC genes among these 65 strains were investigated by PCR. RESULTS: From multi PCR detection, 42 isolates belonged to C. jejuni, other 23 isolates belong to C. coli. Data showing the identification were 100% in concordance with the separated PCR for hipO and glyA amplification. The efficiency (100%) of identification by these three primers multi-PCR method was higher than the biochemical test (83.1%). The cadF and flaA genes were detected from 100% (65/65) of the isolates and the PCR product of each gene were identical with each isolate. Only 10.8% (7/65) of the isolates were positive for virB11. The cdtA gene was found in 92% (60/65) of the isolates. 97.6% (41/42) of C. jejuni had cdtB gene, whereas no PCR product with this primers for all the C. coli isolates. cdtC was presented in all the isolates but the lengths of PCR products were different. For C. jejuni, it was 555 bp, for C. coli, it was about 465 bp. CONCLUSION: This three primers simultaneous multi-PCR method seemed to be useful for the identification of C. jejuni and C. coli isolates from China since cadF and flaA genes were widely spread in Campylobacter isolates in this country. The present report on virB11 was similar to previous reports from other countries, but the distribution of cdt gene cluster in Campylobacter species isolated from China might be different. PMID- 17850714 TI - ? PMID- 17850713 TI - [Study on the carbapenemase genotype and molecular epidemiology of Acinetobacter baumannii]. AB - OBJECTIVE: To investigate antibiotic resistance, clonal relatedness and carbapenemase genotype among carbapenem-resistant Acinetobacter baumannii collected from 3 comprehensive hospitals in Ningbo city, Zhejiang province. METHODS: 28 strains of carbapenem resistant Acinetobacter baumannii were collected from Ningbo Li Hui-li Hospital, Ningbo Li Hui-li Hospital, Ningbo First Hospital, and N ingbo Second Hospital. The minimum inhibitory concentrations (MIC) of these strains were examined by agar dilution and E-test method. Homology of these isolates was analyzed by pulse-field gel electrophoresis (PFGE) and Genotype of carbapenemases were analyzed by PCR and verified by DNA sequencing. RESULTS: 28 strains of Acinetobacter baumanii were highly resistant to all of the antibiotics except polymyxin E. They were classified into 4 clones based on PFGE pattern. Clone A and B had been spreading widely. All of the 28 strains produced carbapenemases which were confirmed as OXA-23 by PCR and sequencing. Metallo-beta lactamase was not detected in any of the isolates. CONCLUSION: All of t hecarbapenem-resistant Acinetobacter baumannii collected from Ningbo were producing OXA-23 carbapenemase, suggesting that the transmission of clones had occurred in the 3 hospitals. PMID- 17850715 TI - [Study on the detection of positive selected codons on HA1 sequence of human influenza A subtype H3N2]. AB - OBJECTIVE: To elucidate the evolution pattern of human influenza virus A H3 subtype by detecting positive selected codons in hemagglutinin gene. METHODS: All H3 sequences in NCBI GenBank and influenza sequence database were downloaded and two step cluster method was applied to divide sequences into six groups, which were corresponding to different period by turns. Fixed Effect Model was applied to detect positive selected codons in each group, and two step cluster method was then used again to summarize variation patterns of selective pressure among sites. RESULTS: Positive selected codons were different in groups corresponding different periods. 50 amino acid codons had been identified as positive selected sites in at least one time span. Among them, 42 codons belonged to one of the five known antigen-combinng regions. A larger amount of sites as well as relatively higher selection pressure were identified in antibody combining regions A and B. Results showed that the 50 sites could be divided into seven different patterns. While other six patterns corresponding to positive selected codons at only one time span, the sites of the seventh pattern were under positive selection in several periods. CONCLUSION: Positive selection codons in evolution of H3A1 strains were alternated in different time period whereas antibody combining regions A and B played more important roles in the evolution process. Other 8 identified codons out of the antibody combining regions might belong to unknown antigen regions. PMID- 17850716 TI - [A retrospective study on the survival rate and risk factors of mortality among 617 inpatients with ischemic stroke]. AB - OBJECTIVE: The purpose of this study was to describe survival status and risk factors of mortality on inpatients with ischemic stroke. METHODS: 617 patients with continuous ischemic stroke cases were collected from January 2002 to June 2005 retrospectively in the Department of Neurology, Xijing Hospital, Fourth Military Medical University. In order to perceive relevant information on survival and the cause of death. All patients were followed through phone calls or mailing. The follow-up program was completed in January 2006. Kaplan-Meier methods were used for survival description. Monovariant and multivariant Cox's proportional hazard regression model were used to analyze prognostic factors on mortality. RESULTS: The longest time in the follow-up program was 47 months with 59 dropped-out cases, making the dropout rate as 9.5%. Of these patients, 80 cases died during the period of study(60 for ischemic stroke,3 for cerebral hemorrhage, 10 for cardiac disease, 7 for other cause). The median survival time was 42. 16 months. The survival rates of one-year, two-year and three-year period were 91.9%, 89.4% and 85.3%, respectively. Monovariant and multivariant Cox's proportional hazard regression model showed that the risk factors associated with mortality were old age (RR = 1.043, 95% CI: 1.013-1.074), lower Glasgow scores (RR = 0.855, 95% CI: 0.742-0.985) ,poor conscious levels(RR = 4.085, 95% CI: 2.128-7.844) and having complication (RR = 1.765, 95% CI: 1.108-2.812). CONCLUSION: The results of this study suggested that the risk factors were old age, lower Glasgow scores, poor conscious levels and having complication on mortality of ischemic stroke. PMID- 17850717 TI - [Study on the association between STK15 Phe31Ile polymorphisms and esophageal squamous cell carcinoma]. AB - OBJECTIVE: To study the relation between single nucleotide polymorphism(SNP) at the 91T-->A(Phe31Ile) position of the STK15 gene and the susceptibility of esophageal squamous cell carcinoma (ESCC) in She county--a ESCC high incidence region in North China. METHODS: Polymerase-chain reaction(PCR)-restriction fragment length polymorphism (RFLP) analysis was used to detect the genotypes of STKl5 Phe31Ile(91T-->A) SNP, and the samples came from 296 ESCC patients and 302 healthy controls. RESULTS: The risk of ESCC significantly increased in the group which had been smoking or having a family history of upper gastrointestinal cancer (UGIC) (the OR = 1.68 and 1.77, 95% CI: 1.34-2.10 and 1.44-2.19, respectively). Rates of the three genotypes (Phe/Phe, Phe/Ile, Ile/Ile) of the STK15 Phe31Ile (91T-->A) SNPs in ESCC patients were 11.5%, 34.8% and 53.7%, respectively, and were not significantly different from that in the healthy group (11.9%, 36.8% and 51.3%) (chi2 = 0.35, P = 0.84). When compared to Phe/Phe genotype, Phe/Ile and Ile/Ile of STK15 91T-->A(Phe31Ile)did not show effect on the risk of ESCC according to the odds ratio results which were 0.98 (95% CI: 0.57-1.69) and 1.09 (0.65-1.82) respectively. STK15 91T-->A (Phe31Ile) SNP also did not significantly influence on the development of ESCC even the samples were stratified by sex, smoking status and family history of upper gastrointestinal cancer. CONCLUSION: The STK15 Phe31Ile(91T-->A) polymorphisms seemed irrelevant with the risk of ESCC in She county. PMID- 17850718 TI - [An applied multilevel model used in the study on behavior of smoking]. AB - OBJECTIVE: To introduce the nature and its application of a multilevel model. METHODS: Data was analyzed from a baseline survey of smoking behavior among middle school students sponsored by a WHO smoking controll project. Multilevel analysis was used on available data and to compare the results from logistic regression. RESULTS: The outcomes of null multilevel model approved that there was hierarchical structure on data. The influencing factors of middle school students smoking appeared to be gender, age, attitude, environment and public education at schools. When the variable of public education by classes was not included, the standard errors by multilevel analysis became smaller than the corresponding standard errors through logistic regression method. CONCLUSION: Multilevel model seemed a good method for analyzing data with hierarchical or cluster structure, it could be applied in stratified or cluster sampling of epidemiological or community-based investigation. PMID- 17850719 TI - [Research advancement of human Streptococcus suis epidemiology]. PMID- 17850721 TI - ? PMID- 17850722 TI - ? PMID- 17850720 TI - [Progress on the study of disease burden and economic impact of next influenza pandemic]. PMID- 17850723 TI - [Multivariate analysis on the relationship between G protein beta3 subunit gene 825C/T polymorphism and essential hypertension]. PMID- 17850724 TI - [Analysis on the status of hepatitis B vaccine rate in floating among one-year old children]. PMID- 17850725 TI - ? PMID- 17850726 TI - Streptococcus penumoniae meningitis. Clinical and experimental studies. PMID- 17850727 TI - Acute stroke--a dynamic process. PMID- 17850728 TI - The pattern of contact with general practice and casualty departments of immigrants and non-immigrants in Copenhagen, Denmark. AB - In the past 30 years Denmark has experienced immigration from non-Western countries, but little is known about immigrants' use of health care. The purpose of this study was to compare and quantify the contact patterns with general practice and casualty departments of immigrants of non-Western origin and non immigrants in Copenhagen City, Denmark. Descriptive register-based study including 2,041,454 daytime contacts in general practice, 202,179 out-of-hours services and 112,733 attendances to casualty departments by 423,201 inhabitants living in Copenhagen throughout 1998. The data was analyzed using Poisson regression models. Immigrants and non-immigrants showed in broad outline the same sex and age-related pattern of contact except for ages above 60 years, where the pattern was more inconclusive. Children of immigrants aged 1-18 years had lower contact rates than non-immigrants during the daytime and in the out-of-hours services/casualty departments. Most immigrant groups aged 19-59 years made greater use of both daytime and out-of-hours services/casualty departments, especially males from Lebanon and the stateless, than non-immigrants, but the level of contact rates varied according to country of origin. The share of telephone consultations in the daytime and the out-of-hours service was much lower for immigrants than for non-immigrants. Marked differences between immigrants and non-immigrants' use of health care services were related to age and country of origin. More research is needed to explain these findings. PMID- 17850732 TI - What's in a name? A paradigm shift for clinical research. PMID- 17850733 TI - Clinical research and drug development in Latin America: weighing the pros and cons, talking about the future. AB - Two decades ago, clinical trials were carried out only in developed countries. Drug development and the need to speed up clinical trials lead the conduction of clinical trials to other countries. Among the regions of interest, Latin America (LA) has played its role successfully. LA has a large number of naive patients, qualified investigators, established regulatory systems and reasonable costs. Furthermore, LA might be also considered as a new option for any company looking for international patterns on drug research and development. The region has good professionals with scientific qualifications, well-established multinational pharmaceutical bases and an expansive pharmaceutical regional market. This work summarizes the recent advances that have occurred in drug research and development in the region and the expansion of the clinical trial market in the last couple of years. PMID- 17850734 TI - Effect of pioglitazone therapy on myocardial and hepatic steatosis in insulin treated patients with type 2 diabetes. AB - High levels of myocardial and hepatic triglyceride are common in obesity and type 2 diabetes. Monotherapy with thiazolidinedione agents reduces hepatic steatosis by up to 50% in patients with type 2 diabetes. It is not known if treatment with a thiazolidinedione added to insulin has a similar beneficial antisteatotic effect. The aim of our study was to determine whether the addition of pioglitazone to insulin treatment in patients with type 2 diabetes has antisteatotic action in the heart and the liver. Thirty-two patients were randomized to 6 months of treatment with insulin or insulin plus pioglitazone. In addition to blood tests, we evaluated myocardial and hepatic triglyceride content, as well as subcutaneous and visceral fat mass at the L2 level, by magnetic resonance spectroscopy and imaging, respectively. Despite weight and subcutaneous fat mass gain, hemoglobin A1c was significantly reduced by both treatments. Myocardial and hepatic triglyceride contents were reduced by the treatment with pioglitazone plus insulin (p = .02 and .03, respectively) but not by the treatment with insulin. Systolic and diastolic blood pressure and heart function remained unchanged in both groups. The addition of pioglitazone to insulin therapy reduced myocardial and hepatic steatosis, consistent with the reported ability of the thiazolidinedione agents to redistribute fat from nonadipose to subcutaneous adipose depots. PMID- 17850735 TI - Relationship of apolipoprotein B levels to the number of risk factors for metabolic syndrome. AB - Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid lowering therapy. However, all lipoproteins containing apolipoprotein B (apo B) appear to be atherogenic. Preferred targets of therapy therefore may include either the cholesterol in all apo B-containing lipoproteins (non-high-density lipoprotein cholesterol [non-HDL-C]) or total apo B itself. Apo B can be measured by three methods: chemically, by nuclear magnetic resonance (NMR), and by immunoassay. This study compares the first two methods as a function of the number of metabolic risk factors in patients with metabolic syndrome. Plasma lipid, lipoprotein cholesterol, and apo B levels were measured in 274 adults with varying numbers of metabolic syndrome components. Low-density lipoprotein (LDL) particle sizes were measured by gel electrophoresis and by NMR. Total apo B was estimated chemically and by conversion of NMR lipoprotein particle number, assuming one apo B molecule per lipoprotein particle. As the number of metabolic syndrome components increased, apo B rose by both chemical and NMR methods, but by chemical methods, increases were in the triglyceride-rich fraction, whereas by NMR, they were in LDL. The correlation between total apo B measured by the two methods was only moderate (r = .73). Further, non-HDL-C was more highly correlated with total apo B measured chemically than either LDL-C or total apo B by NMR. Non-HDL-C correlates highly with total apo B in patients with metabolic syndrome and had advantages as a target of therapy over LDL-C or NMR apo B. PMID- 17850736 TI - Catabolism of glycoconjugates in chronic otitis media with cholesteatoma. AB - Chronic ear disease with cholesteatoma is characterized by an intrusion of keratinizing stratified squamous epithelium into the middle ear manifesting bone resorption at the interface of the perimatrix. The aim of our study was to investigate the markers of a catabolic process associated with several chronic inflammatory states. We assessed the level of catabolism of glycoconjugates in assays of cholesteatoma extracts, quantifying two lysosomal exoglycosidases: alpha-mannosidase (alpha-MAN) and beta-galactosidase (beta-GAL). Cholesteatomas (n = 15) and normal adult postauricular skin served as controls (n = 15) were collected from the patients during surgery owing to chronic otitis media. To assess exoglycosidase activity, release of p-nitrophenol from p-nitrophenol derivatives of alpha-mannose and beta-galactose was used. In 13 of 15 specimens, we observed significantly higher activity of investigated enzymes in cholesteatoma tissue compared with control tissue (postauricular skin). The mean activity of alpha-MAN from the cholesteatoma cells was 1.76 +/- 1.10 nkat/g wet tissue and 0.61 +/- 0.21 nkat/g wet tissue in the control probes. The mean activity of beta-GAL from the cholesteatoma cells was 1.77 +/- 1.07 nkat/g wet tissue and 0.87 +/- 0.20 nkat/g wet tissue in the control probes. Catabolic reactions involving glycoproteins, glycolipids, and proteoglycans may play a role in cholesteatoma-related bone resorption. The present data indicating that the lysosomal exoglycosidases alpha-MAN and beta-GAL are significantly and consistently elevated suggest the need to further correlations assessment between levels of alpha-MAN and beta-GAL and cholesteatoma behavior. Further research should also evaluate the relative importance of these particular exoglycosidases in manifesting bone resorption in considering the spectrum of identified inflammatory mediators. PMID- 17850737 TI - Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients with breast cancer and effects on prognostic factors. AB - The aims of the present study were to investigate the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in breast cancer patients and the association between ACE genotypes and clinicopathologic features, as well as their effects on prognosis. We assessed the I/D polymophism of the ACE gene by using polymerase chain reaction from peripheral blood in breast cancer and healthy age-matched women. The clinicopathologic parameters of breast cancer patients were obtained from medical records. Of the 57 patients, 31 (54.4%) had DD, 24 (42.1%) had ID, and 2 (3.5%) had II genotypes. In control subjects, 33 (63.5%) had DD, 12 (23.1%) had ID, and 7 (13.4%) had II genotypes. The ID genotype was seen more commonly in breast cancer patients (p = .03). When the combination of ID and II genotypes was used as a reference group, the DD genotype was associated with negative hormone receptor status (p = .003), tumor size (p = .054), and lymph node involvement (p = .07) but not histologic high grade and c-erb B2 overexpression. These results suggest that the DD genotype may accompany poor prognostic factors and influence the tumor course. PMID- 17850739 TI - Cyclic nucleotide-regulated ion channels: spotlight on symmetry. AB - In this issue of Structure, Chiu et al. (2007) report the 16 A EM structure of the prokaryotic cyclic nucleotide-regulated K(+) channel MloK1. This structure reveals that the channel is arranged as a four-fold symmetric tetramer. PMID- 17850740 TI - How to get all "A"s in polyadenylation. AB - In an elegant study in this issue of Structure, Balbo and Bohm (2007) report the crystal structure of yeast poly(A) polymerase in a ternary complex with its substrate MgATP and the elongating poly(A) tail, providing molecular insights into the mechanism of polyadenylation. PMID- 17850741 TI - Another window into disordered protein function. AB - Multiple crystal structures of the same proteins often have specific regions that switch between structure and disorder. In this issue of Structure, Zhang et al. (2007) show that these "dual personality fragments" are distinct from both structured and disordered protein and are functionally important. PMID- 17850742 TI - Caught in the act: an ABC transporter on the move. AB - The latest structure of the vitamin B12 permease reported in Science by Hvorup and colleagues represents an unexpected, asymmetric state of an ABC transporter, and indicates that the translocation cycle may be even more complex than previously thought (Hvorup et al., 2007). PMID- 17850743 TI - Structure and function of a chlorella virus-encoded glycosyltransferase. AB - Paramecium bursaria chlorella virus-1 encodes at least five putative glycosyltransferases that are probably involved in the synthesis of the glycan components of the viral major capsid protein. The 1.6 A crystal structure of one of these glycosyltransferases (A64R) has a mixed alpha/beta fold containing a central, six-stranded beta sheet flanked by alpha helices. Crystal structures of A64R, complexed with UDP, CMP, or GDP, established that only UDP bound to A64R in the presence of Mn(2+), consistent with its high structural similarity to glycosyltransferases which utilize UDP as the sugar carrier. The structure of the complex of A64R, UDP-glucose, and Mn(2+) showed that the largest conformational change occurred when hydrogen bonds were formed with the ligands. Unlike UDP glucose, UDP-galactose and UDP-GlcNAc did not bind to A64R, suggesting a selective binding of UDP-glucose. Thus, UDP-glucose is most likely the sugar donor for A64R, consistent with glucose occurring in the virus major capsid protein glycans. PMID- 17850744 TI - Ensemble refinement of protein crystal structures: validation and application. AB - X-ray crystallography typically uses a single set of coordinates and B factors to describe macromolecular conformations. Refinement of multiple copies of the entire structure has been previously used in specific cases as an alternative means of representing structural flexibility. Here, we systematically validate this method by using simulated diffraction data, and we find that ensemble refinement produces better representations of the distributions of atomic positions in the simulated structures than single-conformer refinements. Comparison of principal components calculated from the refined ensembles and simulations shows that concerted motions are captured locally, but that correlations dissipate over long distances. Ensemble refinement is also used on 50 experimental structures of varying resolution and leads to decreases in R(free) values, implying that improvements in the representation of flexibility observed for the simulated structures may apply to real structures. These gains are essentially independent of resolution or data-to-parameter ratio, suggesting that even structures at moderate resolution can benefit from ensemble refinement. PMID- 17850745 TI - The structure of the prokaryotic cyclic nucleotide-modulated potassium channel MloK1 at 16 A resolution. AB - The gating ring of cyclic nucleotide-modulated channels is proposed to be either a two-fold symmetric dimer of dimers or a four-fold symmetric tetramer based on high-resolution structure data of soluble cyclic nucleotide-binding domains and functional data on intact channels. We addressed this controversy by obtaining structural data on an intact, full-length, cyclic nucleotide-modulated potassium channel, MloK1, from Mesorhizobium loti, which also features a putative voltage sensor. We present here the 3D single-particle structure by transmission electron microscopy and the projection map of membrane-reconstituted 2D crystals of MloK1 in the presence of cAMP. Our data show a four-fold symmetric arrangement of the CNBDs, separated by discrete gaps. A homology model for full-length MloK1 suggests a vertical orientation for the CNBDs. The 2D crystal packing in the membrane-embedded state is compatible with the S1-S4 domains in the vertical "up" state. PMID- 17850746 TI - Structural insights into the interaction of insulin-like growth factor 2 with IGF2R domain 11. AB - The insulin-like growth factor II/mannose-6-phosphate receptor (IGF2R) mediates trafficking of mannose-6-phosphate (M6P)-containing proteins and the mitogenic hormone IGF2. IGF2R also plays an important role as a tumor suppressor, as mutation is frequently associated with human carcinogenesis. IGF2 binds to domain 11, one of 15 extracellular domains on IGF2R. The crystal structure of domain 11 and the solution structure of IGF2 have been reported, but, to date, there has been limited success when using crystallography to study the interaction of IGFs with their binding partners. As an approach to investigate the interaction between IGF2 and IGF2R, we have used heteronuclear NMR in combination with existing mutagenesis data to derive models of the domain 11-IGF2 complex by using the program HADDOCK. The models reveal that the molecular interaction is driven by critical hydrophobic residues on IGF2 and IGF2R, while a ring of flexible, charged residues on IGF2R may modulate binding. PMID- 17850747 TI - Functional linkages can reveal protein complexes for structure determination. AB - In the study of protein complexes, is there a computational method for inferring which combinations of proteins in an organism are likely to form a crystallizable complex? Here we attempt to answer this question, using the Protein Data Bank (PDB) to assess the usefulness of inferred functional protein linkages from the Prolinks database. We find that of the 242 nonredundant prokaryotic protein complexes shared between the current PDB and Prolinks, 44% (107/242) contain proteins linked at high confidence by one or more methods of computed functional linkages. Similarly, high-confidence linkages detect 47% of known Escherichia coli protein complexes, with 45% accuracy. Together these findings suggest that functional linkages will be useful in defining protein complexes for structural studies, including for structural genomics. We offer a database of inferred linkages corresponding to likely protein complexes for some 629,952 pairs of proteins in 154 prokaryotes and archaea. PMID- 17850748 TI - Fragile X mental retardation syndrome: structure of the KH1-KH2 domains of fragile X mental retardation protein. AB - Fragile X syndrome is the most common form of inherited mental retardation in humans, with an estimated prevalence of about 1 in 4000 males. Although several observations indicate that the absence of functional Fragile X Mental Retardation Protein (FMRP) is the underlying basis of Fragile X syndrome, the structure and function of FMRP are currently unknown. Here, we present an X-ray crystal structure of the tandem KH domains of human FMRP, which reveals the relative orientation of the KH1 and KH2 domains and the location of residue Ile304, whose mutation to Asn is associated with a particularly severe incidence of Fragile X syndrome. We show that the Ile304Asn mutation both perturbs the structure and destabilizes the protein. PMID- 17850749 TI - Cryo-EM study of the Pseudomonas bacteriophage phiKZ. AB - The phiKZ virus is one of the largest known bacteriophages. It infects Pseudomonas aeruginosa, which is frequently pathogenic in humans, and, therefore, has potential for phage therapy. The phiKZ virion consists of an approximately 1450 A diameter icosahedral head and an approximately 2000 A long contractile tail. The structure of the phiKZ tail has been determined using cryo-electron microscopy. The phiKZ tail is much longer than that of bacteriophage T4. However, the helical parameters of their contractile sheaths, surrounding their tail tubes, are comparable. Although there is no recognizable sequence similarity between the phiKZ and T4 tail sheath proteins, they are similar in size and shape, suggesting that they evolved from a common ancestor. The phiKZ baseplate is significantly larger than that of T4 and has a flatter shape. Nevertheless, phiKZ, similar to T4, has a cell-puncturing device in the middle of its baseplate. PMID- 17850750 TI - Study of recombinant antibody fragments and PAI-1 complexes combining protein protein docking and results from site-directed mutagenesis. AB - Elevated plasma levels of plasminogen activator inhibitor-1 (PAI-1) have been correlated with cardiovascular diseases such as myocardial infarction and venous thrombosis. PAI-1 has also been shown to play an important role in tumor development, diabetes, and obesitas. Monoclonal antibodies MA-8H9D4 and MA 56A7C10, and their single-chain variable fragments (scFv), exhibit PAI-1 neutralizing properties. In this study, a rigid-body docking approach is used to predict the binding geometry of two distinct conformations of PAI-1 (active and latent) in complex with these antibody fragments. Resulting models were initially refined by using the dead-end elimination algorithm. Different filtering criteria based on the mutagenesis studies and structural considerations were applied to select the final models. These were refined by using the slow-cooling torsion angle dynamic annealing protocol. The docked structures reveal the respective epitopes and paratopes and their potential interactions. This study provides crucial information that is necessary for the rational development of low molecular weight PAI-1 inhibitors. PMID- 17850751 TI - Mechanism of poly(A) polymerase: structure of the enzyme-MgATP-RNA ternary complex and kinetic analysis. AB - We report the 1.8 A structure of yeast poly(A) polymerase (PAP) trapped in complex with ATP and a five residue poly(A) by mutation of the catalytically required aspartic acid 154 to alanine. The enzyme has undergone significant domain movement and reveals a closed conformation with extensive interactions between the substrates and all three polymerase domains. Both substrates and 31 buried water molecules are enclosed within a central cavity that is open at both ends. Four PAP mutants were subjected to detailed kinetic analysis, and studies of the adenylyltransfer (forward), pyrophosphorolysis (reverse), and nucleotidyltransfer reaction utilizing CTP for the mutants are presented. The results support a model in which binding of both poly(A) and the correct nucleotide, MgATP, induces a conformational change, resulting in formation of a stable, closed enzyme state. Thermodynamic considerations of the data are discussed as they pertain to domain closure, substrate specificity, and catalytic strategies utilized by PAP. PMID- 17850752 TI - A structural characterization of human SCO2. AB - Human Sco2 is a mitochondrial membrane-bound protein involved in copper supply for the assembly of cytochrome c oxidase in eukaryotes. Its precise action is not yet understood. We report here a structural and dynamic characterization by NMR of the apo and copper(I) forms of the soluble fragment. The structural and metal binding features of human Cu(I)Sco2 are similar to the more often studied Sco1 homolog, although the dynamic properties and the conformational disorder are quite different when the apo forms and the copper(I)-loaded forms of the two proteins are compared separately. Such differences are accounted for in terms of the different physicochemical properties in strategic protein locations. The misfunction of the known pathogenic mutations is discussed on the basis of the obtained structure. PMID- 17850753 TI - Between order and disorder in protein structures: analysis of "dual personality" fragments in proteins. AB - In their natural environment, three-dimensional structures of proteins undergo significant fluctuations and are often partially or completely disordered. This phenomenon recently became the focus of much attention, as many proteins, especially from higher organisms, were shown to contain large intrinsically disordered regions. Such disordered regions may become ordered only under very specific circumstances, if at all, and can be recognized by specific amino acid composition and sequence signatures. Here, we suggest that the balance between order and disorder is much more subtle in that many regions are very close to the order/disorder boundary. Specifically, analysis of redundant sets of experimental models of protein structures, where emphasis is put on comparison of structures of identical proteins solved in different conditions and functional states, shows hundreds of fragments captured in two states: ordered and disordered. We show that such fragments, which we call here "dual personality" (DP) fragments, have distinctive features that differentiate them from both regularly folded and intrinsically disordered fragments. We hypothesize, and show on several examples, that such fragments are often targets of regulation, either by allostery or posttranslational modifications. PMID- 17850754 TI - Bombyx mori pheromone-binding protein binding nonpheromone ligands: implications for pheromone recognition. AB - Insect pheromone-binding proteins (PBPs) transport sex pheromones through the aqueous layer surrounding G protein-coupled receptors that initiate signaling events leading to mating. This PBP-receptor system strongly discriminates between ligands with subtle structural differences, but it has proved difficult to distinguish the degree of discrimination of the PBP from that of the G protein coupled receptor. The three-dimensional structures of the PBP of Bombyx mori, the silkworm moth, both with and without its cognate ligand bombykol ([E,Z]-10,12 hexadecadienol), have been determined by X-ray crystallography and NMR. In this paper, the structures of the same binding protein with bound iodohexadecane and bell pepper odorant were determined at 1.9 and 2.0 A, respectively. These structures illustrate the remarkable plasticity in the ligand binding site of the PBP, but suggest the protein might still act as a filter during pheromone signal processing. PMID- 17850755 TI - Simultaneous processing of visual information and planning of hand movements in a visuo-manual search task. AB - When searching for a target with eye movements, saccades are planned and initiated while the visual information is still being processed. If hand movements are needed to perform a search task, can they too be planned while visual information from the current position is still being processed? To find out we studied a visual search task in which participants had to move their hand to shift a window through which they could see the items. The task was to find an O in a circle of Cs. The size of the window and the sizes of the gaps in the Cs were varied. Participants made fast, smooth arm movements between items and adjusted their movements, when on the items, to the window size. On many trials the window passed the target and returned, indicating that the next movement had been planned before identifying the item that was in view. PMID- 17850756 TI - Schistosoma mansoni: gene expression of the nucleotide excision repair factor 2 (NEF2) during the parasite life cycle, and in adult worms after exposure to different DNA-damaging agents. AB - DNA is often damaged by many environmental agents, which lead to the up regulation of several genes involved in different repair pathways. Schistosoma mansoni has a complex life cycle, being exposed to a subset of DNA-damaging agents, such as those present in the environment and host immune response. Recently, studies showed that nucleotide excision repair (NER) is an indispensable mechanism for removing a broad spectrum of different DNA lesions. In the present report, we showed the gene expression of nucleotide excision repair factor 2 (NEF2) SmRad23 and SmRad4, in different developmental stages of S. mansoni, as well as the differential expression of these genes in S. mansoni adult worms treated with DNA-damaging agents. Furthermore, it was revealed the correlation of these genes with their orthologues in other eukaryotes. Our reports suggest that NER is an important repair pathway during the complex life cycle of S. mansoni. PMID- 17850757 TI - Electrotransfer of proteins in an environmentally friendly methanol-free transfer buffer. AB - Western blot transfer buffer was modified to substitute the acute poison methanol, with the common rubbing alcohol, isopropanol in concentrations of as low as 5 % for protein electrotransfer. Commercially available molecular weight markers and rabbit serum were run on polyacrylamide gels and shown to be transferred adequately to both nitrocellulose and polyvinylidene difluoride membranes under either wet or semi-dry conditions with similar results in all cases. This procedure was successfully used for immunodetection of the rabbit IgG heavy chain from serum. Therefore, this represents a good alternative for less toxic and environmentally friendly conditions for western immunoblotting of proteins. PMID- 17850758 TI - Endocrine function in a 48,XXYY adult with type 2 diabetes: case report with a review of the literature. AB - We present the clinical, biological, endocrinal and psychological characteristics of a 48,XXYY adult. The 43-year-old male examined is the first reported case of this XY polysomy concomitant with type 2 diabetes. Endocrine investigations suggested dysfunction of Leydig and Sertoli cells whereas the pituitary function appeared normal. We compare the phenotypic, behavioral and pathological features of the syndrome in our patient with other reports in the literature. PMID- 17850759 TI - [A radiological case of sinusology: a schwannoma localized in the sinuses]. AB - INTRODUCTION: In daily practice, the otorhinolaryngologist may face cases of facial tumors of sinonasal origin. Their diagnosis remains difficult based on clinical findings alone. Therefore, imaging techniques can guide the surgeon toward the correct diagnosis. METHODS: A 14-year-old male presented with a history of headaches and nasal obstruction. Physical examination revealed a mass in the right nasal fossa. RESULTS: A computed tomography scan showed an isodense lesion in the posterior half of the right nasal fossa, extending into the maxillary sinus, orbital floor, pterygopalatine fossa, and infratemporal fossa. Magnetic resonance imaging showed great enhancement upon gadolinium administration. The diagnosis of schwannoma was suggested after angiography was performed. The tumor was then resected via a transfacial approach with maxillozygomatic osteotomy. Pathologic examination confirmed the diagnosis of schwannoma. CONCLUSION: The definite diagnosis of a sinonasal tumor can be confirmed only histologically. However, preoperative radiological data can direct the surgeon toward the correct diagnosis and above all the most appropriate surgical approach. PMID- 17850760 TI - Ergonomic effects of load carriage on the upper and lower back on metabolic energy cost of walking. AB - We examined the effects of load carriage position on the energy cost of walking defined as the ratio of the 2-min steady-state oxygen consumption to the speed and economical speed. Fourteen healthy men walked on a treadmill at various speeds without and with load on the lower and upper back, which corresponded to 15% of their body mass. The energy cost of walking significantly decreased during walking with load than without load at slower speeds. A significant decrease in the energy cost of walking was also observed while carrying the load on the upper back than on the lower back at 60-80 m/min. The economical speed significantly decreased when carrying the load on the upper and lower back, and it was significantly correlated with body height. These findings suggest that an optimal carrying method is evident to reduce physical stress during walking with loads. PMID- 17850761 TI - Modelling relationships between cognitive variables during and following public speaking in participants with social phobia. AB - Cognitive models of social phobia predict that several cognitive processes will mediate the relationship between trait levels of social anxiety and the extent of anxiety experienced in a specific social-evaluative situation. The current study aimed to provide a test of these relationships. Over 200 clinical participants with social phobia completed measures of their general social anxiety and a week later performed a brief impromptu speech. They completed a measure of state anxiety in response to the speech as well as questionnaires assessing several cognitive constructs including focus of perceived attention, perceived performance, and probability and cost of negative evaluation. A week later, they completed measures of negative rumination experienced over the week, as well as a measure of the recollection of their perceived performance. Path analysis provided support for a model in which the cognitive factors mediated between general social anxiety and the degree of anxiety experienced in response to the speech. A second model supported the theory that negative rumination mediated between characteristic social anxiety and negative bias in the recollection of performance. PMID- 17850762 TI - Aromatic residues of Caveolin-1 binding motif of alpha-hemolysin are essential for membrane penetration. AB - We have created single cysteine Caveolin-1 binding motif mutants (SCCBMMs) of staphylococcal alpha-HL for understanding assembly and penetration. All SCCBMMs have normal folding like alpha-HL as examined by limited proteolysis, intrinsic fluorescence emission, no hemolytic activity and do not form hetero oligomers with alpha-HL indicating that the conformational changes occurred at the cell membrane are different to that of alpha-HL. While modification of SCCBMMs with a membrane impermeant reagent has resulted in reduced binding, badan modification has resulted in the enhancement of badan fluorescence with time of assembly (incubation time) indicating the change in environment of the badan and the need for the penetration of the aromatic amino acids. Our studies indicate that the conformational changes are probably initiated at the Caveolin-1 binding motif and provide a basis for differential mode of interaction of the Caveolin-1 binding motif depending upon the nature of the target cell membrane. PMID- 17850763 TI - Dynamic SPR monitoring of yeast nuclear protein binding to a cis-regulatory element. AB - Gene expression is controlled by protein complexes binding to short specific sequences of DNA, called cis-regulatory elements. Expression of most eukaryotic genes is controlled by dozens of these elements. Comprehensive identification and monitoring of these elements is a major goal of genomics. In pursuit of this goal, we are developing a surface plasmon resonance (SPR) based assay to identify and monitor cis-regulatory elements. To test whether we could reliably monitor protein binding to a regulatory element, we immobilized a 16bp region of Saccharomyces cerevisiae chromosome 5 onto a gold surface. This 16bp region of DNA is known to bind several proteins and thought to control expression of the gene RNR1, which varies through the cell cycle. We synchronized yeast cell cultures, and then sampled these cultures at a regular interval. These samples were processed to purify nuclear lysate, which was then exposed to the sensor. We found that nuclear protein binds this particular element of DNA at a significantly higher rate (as compared to unsynchronized cells) during G1 phase. Other time points show levels of DNA-nuclear protein binding similar to the unsynchronized control. We also measured the apparent association complex of the binding to be 0.014s(-1). We conclude that (1) SPR-based assays can monitor DNA nuclear protein binding and that (2) for this particular cis-regulatory element, maximum DNA-nuclear protein binding occurs during G1 phase. PMID- 17850764 TI - Protein synthesis in liposomes with a minimal set of enzymes. AB - In a significant step towards the construction of the semi-synthetic minimal cell, a protein expression system with a minimal set of pure and specific enzymes is required. A novel cell-free transcription and translation system named PURESYSTEM (PS), consisting of a specified set of 36 enzymes and ribosomes, has been entrapped in POPC liposomes for protein synthesis. The PS has been used to transcribe and translate an Enhanced Green Fluorescent Protein (EGFP) gene from plasmid DNA. The synthesis is confirmed by the EGFP fluorescence emitting liposomes on fluorometric analysis and on confocal microscopy analysis. Furthermore the PS encapsulated into POPC liposomes can drive the expression of the plsB and plsC genes encoding for the sn-glycerol-3-phosphate acyltransferase (GPAT) and 1-acyl-sn-glycerol-3-phosphate acyltransferase (LPAAT) involved in the first step of the "salvage pathway" for synthesis of POPC. The expression of GPAT and LPAAT in liposomes would in principle allow the production of the cell boundary from within. PMID- 17850765 TI - Interactions of TRF2 with model telomeric ends. AB - Telomeres are DNA-protein complexes at the ends of eukaryotic chromosomes, the integrity of which is essential for chromosome stability. An important telomere binding protein, TTAGGG repeat factor 2 (TRF2), is thought to protect telomere ends by remodeling them into T-loops. We show that TRF2 specifically interacts with telomeric ss/ds DNA junctions and binding is sensitive to the sequence of the 3', guanine-strand (G-strand) overhang and double-stranded DNA sequence at the junction. Association of TRF2 with DNA junctions hinders cleavage by exonuclease T. TRF2 interactions with the G-strand overhang do not involve the TRF2 DNA binding domain or the linker region. However, mobility shifts and atomic force microscopy show that the previously uncharacterized linker region is involved in DNA-specific, TRF2 oligomerization. We suggest that T-loop formation at telomere ends involves TRF2 binding to the G-strand overhang and oligomerization through both the known TRFH domain and the linker region. PMID- 17850766 TI - Requirement for protein kinase R in interleukin-1alpha-stimulated effects in cartilage. AB - Interleukin-1 (IL-1) has pleiotropic effects in cartilage. The interferon induced, double stranded RNA-activated protein kinase PKR that phosphorylates eukaryotic initiation factor 2 (eIF2) alpha has been implicated in cytokine effects in chondrocytes. A compound was recently identified that potently suppresses PKR autophosphorylation (IC50 approximately 200 etaM) and partially restores PKR-inhibited translation in a cell-free system with significant effect in the nanomolar range. The objectives of this study were to exploit this potent PKR inhibitor to assess whether PKR kinase activity is required for catabolic and proinflammatory effects of IL-1alpha in cartilage and to determine whether IL 1alpha causes an increase in eIF2alpha phosphorylation that is antagonized by the PKR inhibitor. Cartilage explants were incubated with the PKR inhibitor and IL 1alpha. Culture media were assessed for sulfated glycosaminoglycan as an indicator of proteoglycan degradation and for prostaglandin E(2). Cartilage extracts were analyzed by Western blot for cyclooxygenase-2 and phosphorylated signaling molecules. Nanomolar concentrations of the PKR inhibitor suppressed proteoglycan degradation and cyclooxygenase-2 accumulation in IL-1alpha-activated cartilage. The PKR inhibitor stimulated or inhibited PGE(2) production with a biphasic dose response relationship. IL-1alpha increased the phosphorylation of both PKR and eIF2alpha, and nanomolar concentrations of PKR inhibitor suppressed the IL-1alpha-induced changes in phosphorylation. The results strongly support PKR involvement in pathways activated by IL-1alpha in chondrocytes. PMID- 17850767 TI - Behavioral modulation of neuronal calcium/calmodulin-dependent protein kinase II activity: differential effects on nicotine-induced spinal and supraspinal antinociception in mice. AB - Recent studies have implicated the involvement of Ca(2+)-dependent mechanisms, in particular calcium/calmodulin-dependent protein kinase II (CaM kinase II) in nicotine-induced antinociception using the tail-flick test. The spinal cord was suggested as a possible site of this involvement. The present study was undertaken to investigate the hypothesis that similar mechanisms exist for nicotine-induced antinociception in the hot-plate test, a response thought to be centrally mediated. In order to assess these mechanisms, i.c.v. administered CaM kinase II inhibitors were evaluated for their effects on antinociception produced by either i.c.v. or s.c. administration of nicotine in both tests. In addition, nicotine's analgesic effects were tested in mice lacking half of their CaM kinase II (CaM kinase II heterozygous) and compare it to their wild-type counterparts. Our results showed that although structurally unrelated CaM kinase II inhibitors blocked nicotine's effects in the tail-flick test in a dose-related manner, they failed to block the hot-plate responses. In addition, the antinociceptive effects of systemic nicotine in the tail-flick but not the hot-plate test were significantly reduced in CaM kinase II heterozygous mice. These observations indicate that in contrast to the tail-flick response, the mechanism of nicotine induced antinociception in the hot-plate test is not mediated primarily via CaM kinase II-dependent mechanisms at the supraspinal level. PMID- 17850768 TI - Mood and neuroendocrine response to a chemical stressor, metyrapone, in buprenorphine-maintained heroin dependence. AB - BACKGROUND: Heroin dependence is associated with a hyperactive hypothalamic pituitary-adrenal (HPA) axis, proposed as a biological correlate of craving. Maintenance treatment with methadone normalizes HPA axis activity. Here, we examined HPA axis activity under maintenance treatment with the increasingly utilized partial opiate agonist buprenorphine. METHODS: Responses to a metyrapone challenge were compared in 20 buprenorphine-maintained heroin addicts and 20 healthy volunteers (10 received a single 50 mg naltrexone dose [NTX+] and 10 received no naltrexone [NTX-]). Patients were 16 male subjects and 4 female subjects, aged 30 to 38 years, heroin-dependent and relapse-free under buprenorphine maintenance (BUP) for a minimum of 6 months. Healthy volunteers were 9 male subjects and 11 female subjects, aged 36 to 49 years, with no history of dependence. Serial measures were obtained of plasma adrenocorticotropic hormone (ACTH) and cortisol and Profile of Mood States (POMS) ratings over time. Subjects were genotyped for the OPRM1 118A/G polymorphism. RESULTS: Buprenorphine maintenance showed a dampened HPA axis response to metyrapone, with OPRM1 118G carriers showing a significantly attenuated response compared with 118A carriers. The response of the NTX+ group was markedly increased. In contrast, negative affect was elevated in the BUP group but did not differ between NTX- and NTX+. Buprenorphine maintenance and NTX- groups did not differ in positive affect, whereas the NTX+ group was lower. CONCLUSIONS: In contrast to exaggerated HPA axis responsiveness reported in untreated heroin dependence, response to metyrapone was subnormal in heroin addicts maintained on buprenorphine. Despite this, increased measures of negative affect were seen in this group. This implies a dissociation of HPA axis responsiveness and affect in heroin dependence. PMID- 17850769 TI - The expression of Troponin T1 gene is induced by ketamine in adult mouse brain. AB - The glutamatergic system has been implicated in neuropsychiatric disorders, such as schizophrenia, bipolar disorder and Alzheimer's disease, which also have a high prevalence of metabolic syndrome. Treatment with ketamine, a non-competitive glutamate N-methyl-d-aspartic acid (NMDA) receptor antagonist, is known to have paradoxical effects of neuroprotection and neurotoxicity. We investigated gene expression in brain tissue of adult mice treated with ketamine to characterize the expression profiles and to identify the affected metabolic pathways. Adult male mice were treated by a single intraperitoneal (i.p.) injection of either s(+)ketamine (80 mg/kg) or distilled water (as the control). Fifty genes were differentially expressed in ketamine-treated mouse brains compared with control mice using oligonucleotide microarray analysis, and the expression of Troponin T1 (Tnnt1) gene was consistently elevated (2- to 4-fold) (p<0.001). Ketamine-induced Tnnt1 expression was confirmed and characterized using RNA in situ hybridization techniques in paraffin embedded brain tissue sections. Tnnt1 expression was induced in the granule layer of the hippocampus, amygdala, hypothalamus, Purkinje cells of cerebellum (p<0.0001), and cerebral cortex. Tnnt1 gene is known to interact directly with FoxO1, which is involved in multiple peripheral metabolic pathways and central energy homeostasis. Our findings suggest that the induction of Tnnt1 gene expression in adult mouse brains by ketamine may illustrate the genes involved in the metabolic syndromes observed in neuropsychiatric disorders. PMID- 17850771 TI - Effects of systemic PSI administration on catecholaminergic cells in the brain, adrenal medulla and carotid body in Wistar rats. AB - Traditional Parkinson's disease models in rats have several disadvantages. A promising alternative in terms of a more physiological model was proposed by McNaught et al. [McNaught, K.S., Perl, D.P., Brownell, A.L., Olanow, C.W., 2004. Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease. Ann. Neurol. 56, 149-162.] inhibiting the proteasomal protein degradation in vivo where they observed in Sprague-Dawley rats distinct symptoms of Parkinson's disease, a typical slow progredient loss of dopaminergic neurons in the substantia nigra and a lack of dopaminergic afferences in the striatum. We administered to Wistar rats a synthetic proteasome inhibitor (PSI) analogous to the published method. Locomotor changes were analysed by a footprint test. Brain slices containing the substantia nigra and the striatum were stained immunohistochemically against tyrosine hydroxylase, neuronal nuclei antigen, glial fibrillary acidic protein, alpha-synuclein and microglia. Standard histological stainings (haematoxylin eosin or Nissl) were also performed. The proteasome inhibitor effect on the glomerular layer of the olfactory bulb, the adrenal medulla and the carotid body was examined. We observed no PSI-induced motor deficits and loss of tyrosine hydroxylase immunoreactivity in the substantia nigra or the striatum. However, we detected a distinct increase of tyrosine hydroxylase immunoreactivity in the glomerular layer of the olfactory bulb and in the adrenal medulla. Our results fall in line with reports of other research groups which failed to reproduce the original report, but here for the first time McNaughts model could not be reproduced in Wistar rats. The observed effects on the olfactory bulb and peripheral catecholaminergic organs speak for an impermeability of the blood brain barrier for PSI. PMID- 17850770 TI - Early segregation of layered projections from the lateral superior olivary nucleus to the central nucleus of the inferior colliculus in the neonatal cat. AB - The central nucleus of the inferior colliculus (IC) is a laminated structure that receives multiple converging afferent projections. These projections terminate in a layered arrangement and are aligned with dendritic arbors of the predominant disc-shaped neurons, forming fibrodendritic laminae. Within this structural framework, inputs terminate in a precise manner, establishing a mosaic of partially overlapping domains that likely define functional compartments. Although several of these patterned inputs have been described in the adult, relatively little is known about their organization prior to hearing onset. The present study used the lipophilic carbocyanine dyes DiI and DiD to examine the ipsilateral and contralateral projections from the lateral superior olivary (LSO) nucleus to the IC in a developmental series of paraformaldehyde-fixed kitten tissue. By birth, the crossed and uncrossed projections had reached the IC and were distributed across the frequency axis of the central nucleus. At this earliest postnatal stage, projections already exhibited a characteristic banded arrangement similar to that described in the adult. The heaviest terminal fields of the two inputs were always complementary in nature, with the ipsilateral input appearing slightly denser. This early arrangement of interdigitating ipsilateral and contralateral LSO axonal bands that occupy adjacent sublayers supports the idea that the initial establishment of this highly organized mosaic of inputs that defines distinct synaptic domains within the IC occurs largely in the absence of auditory experience. Potential developmental mechanisms that may shape these highly ordered inputs prior to hearing onset are discussed. PMID- 17850772 TI - Two-pore-domain potassium channels contribute to neuronal potassium release and glial potassium buffering in the rat hippocampus. AB - Two-pore-domain potassium (K2P) channels have been suggested to be involved in neuronal K+ release and glial K+ uptake. We studied effects of the K2P channel blockers quinine (200 or 500 microM), quinidine (500 microM), and bupivacaine (200 microM) on stimulus-induced and iontophoretically induced transient increases of the extracellular potassium concentration ([K+]o) in area CA1 of rat hippocampal slices, always in presence of AMPA/kainate and NMDA receptor antagonists. Increases in [K+]o evoked by repetitive alvear stimulation (20 Hz) were blocked by quinine and quinidine but amplitudes of population spikes were only modestly reduced. Bupivacaine suppressed both rises in [K+]o and population spikes. In contrast, iontophoretically induced rises in [K+]o were moderately augmented by quinine and quinidine while bupivacaine had no effect. Barium at concentrations of 2 mM which should block both potassium inward rectifier (Kir) and some K2P channels doubled iontophoretically induced rises in [K+]o also in presence of quinine, quinidine, and bupivacaine. The data suggest that quinine/quinidine-sensitive K2P channels mediate K+ release from neurons and possibly contribute to glial K+ buffering. PMID- 17850773 TI - Variability in the carbazole assay for N-desulfonated/N-acylated heparin derivatives. AB - The carbazole assay is commonly employed to quantify heparin and other uronic acid-containing polysaccharides. Heparin-derived standard curves are often employed to quantify solutions of various natural and unnatural heparin structures that have different levels of sulfate substitution, different levels of N-sulfo and N-acetyl groups, and other structural changes as a consequence of reducing molecular weight. Recent studies in our laboratory have focused on chemically modified heparin derivatives comprised of structurally diverse N-acyl moieties substituted into heparin in place of N-sulfo groups. We report here that although differing degrees of 2-N-sulfo-, 2-N-acetyl- or 2-amino-d-glucosamine residues within heparin do not affect signal intensity in the carbazole assay, replacing N-sulfo groups in heparin with structurally diverse N-acyl moieties affords products that display significant variation in the assay. The structure of different N-acyl groups, and to a lesser extent the degree of N-acylation by individual N-acyl groups, is shown to variably alter signal intensity in the carbazole assay even though content and structure of uronic acid residues is unaltered. PMID- 17850774 TI - The multiple Maillard reactions of ribose and deoxyribose sugars and sugar phosphates. AB - Ribose 5-phosphate (R5P) undergoes the Maillard reaction with amines at significantly higher rates than most other sugars and sugar phosphates. The presence of an intramolecular phosphate group, which catalyzes the early stages of the Maillard reaction, provides the opportunity for the R5P molecule to undergo novel reaction paths creating unique Maillard products. The initial set of reactions leading to an Amadori product (phosphorylated) and to an alpha dicarbonyl phosphate compound follows a typical Maillard reaction sequence, but an observed phosphate hydrolysis accompanying the reaction adds to the complexity of the products formed. The reaction rate for the loss of R5P is partially dependent on the pK(a) of the amine but also is correlated to the protonation of an early intermediate of the reaction sequence. In the presence of oxygen, a carboxymethyl group conjugated to the amine is a major product of the reaction of R5P with N-acetyllysine while little of this product is generated in the absence of oxygen. Despite lacking a critical hydroxyl group necessary for the Maillard reaction, 2-deoxyribose 5-phosphate (dR5P) still generates an Amadori-like product (with a carbonyl on the C-3 carbon) and undergoes phosphate cleavage. Two highly UV-absorbing products of dR5P were amine derivatives of 5-methylene-2 pyrrolone and 2-formylpyrrole. The reaction of dR5P with certain amines generates a set of products that exhibit an interesting absorbance at 340nm and a high fluorescence. PMID- 17850775 TI - Facile synthesis of 1',2'-cis-beta-pyranosyladenine nucleosides. AB - 1',2'-cis-beta-Glycosyladenine nucleosides, such as beta-altroside, beta mannoside, and beta-idoside, were efficiently synthesized from the corresponding 1',2'-trans-beta-6-chloropurine derivatives, beta-glucoside, and beta galactoside. Nucleophilic substitution of the O-trifluoromethanesulfonyl groups at the C-2' and/or 3' was carried out using tetrabutylammonium acetate or cesium acetate under mild conditions. Subsequent deprotection and amidation afforded the desired compounds, 1',2'-cis-beta-pyranosyladenine nucleosides. PMID- 17850776 TI - ERK signaling is a central regulator for BMP-4 dependent capillary sprouting. AB - OBJECTIVE: Bone Morphogenetic Protein-4 (BMP-4) and Extracellular-Signal Regulated Kinases (ERK) play crucial roles in vascular diseases. Here, we demonstrate that BMP-4 not only signals through the classical Smad cascade but also activates ERK phosphorylation as an alternative pathway in human umbilical vein endothelial cells (HUVEC) and that Smad and ERK pathways communicate through signal crosstalk. METHODS: HUVECs were treated with BMP-4 and/or MEK inhibitors. Smad 6 and constitutively active (ca) MEK1 were overexpressed. Loss of function of Smad 4 and Smad 6 was achieved by specific siRNA transfection. Cell lysates were analyzed by western blotting for Smad and ERK phosphorylation. HUVEC spheroids were generated for angiogenesis quantification. RESULTS: Treatment with BMP-4 results in a dose- and time-dependent activation of the MEK-ERK 1/2 pathway in addition to activation of the Smad pathway and is blocked by MEK inhibitors. Quantitative in-gel angiogenesis assays in the presence or absence of MEK inhibitors demonstrate that ERK signals are necessary for BMP-4 induced capillary sprouting. Furthermore sprouting is not blocked by inhibition of the Smad signaling pathway. Overexpression of the inhibitory Smad 6 inhibits ERK phosphorylation and ERK-induced capillary sprouting, whereas loss of function of Smad 4 has no effect. CONCLUSIONS: We demonstrate that ERK1/2 functions as an alternative pathway in BMP-4 signaling in HUVECs. Capillary sprouting induced by BMP-4 is dependent on ERK phosphorylation. ERK is essential for efficient transduction of BMP signals and serves as a positive feedback mechanism. On the other hand, stimulation of Smad 6 inhibits ERK activation and thus results in a negative feedback loop to fine-tune BMP signaling in HUVECs. PMID- 17850777 TI - Plasticity of CD133+ cells: role in pulmonary vascular remodeling. AB - OBJECTIVE: Studies in pulmonary arteries (PA) of patients with chronic obstructive pulmonary disease (COPD) suggest that bone marrow-derived endothelial progenitor cells (CD133(+)) may infiltrate the intima and differentiate into smooth muscle cells (SMC). This study aimed to evaluate the plasticity of CD133(+) cells to differentiate into SMC and endothelial cells (EC) in both cell culture and human isolated PA. METHODS: Plasticity of granulocyte-colony stimulator factor (G-CSF)-mobilized peripheral blood CD133(+) cells was assessed in co-cultures with primary lines of human PA endothelial cells (PAEC) or SMC (PASMC) and in isolated human PA. We also evaluated if the phenotype of differentiated progenitor cells was acquired by fusion or differentiation. RESULTS: The in vitro studies demonstrated CD133(+) cells may acquire the morphology and phenotype of the cells they were co-cultured with. CD133(+) cells co-incubated with human isolated PA were able to migrate into the intima and differentiate into SMC. Progenitor cell differentiation was produced without fusion with mature cells. CONCLUSIONS: We provide evidence of plasticity of CD133(+) cells to differentiate into both endothelial cells and SMC, reinforcing the idea of their potential role in the remodeling process of PA in COPD. This process was conducted by transdifferentiation and not by cell fusion. PMID- 17850778 TI - Dimethylthiourea protects against mitochondrial oxidative damage induced by cisplatin in liver of rats. AB - Cisplatin is one of the most effective chemotherapeutic agents. However, at higher doses liver injury may occur. The purpose of this study was to explore whether the hydroxyl radical scavenger dimethylthiourea (DMTU) protects against cisplatin-induced oxidative damage in vivo and to define the mitochondrial pathways involved in cytoprotection. Adult male Wistar rats (200-220 g) were divided into four groups of eight animals each. The control group was treated only with an intraperitoneal (i.p.) injection of saline solution (1 ml/100 g body weight). The DMTU group was given only DMTU (500 mg/kg body weight, i.p), followed by 125 mg/kg body weight, i.p. (twice a day) until sacrifice. The cisplatin group was given a single injection of cisplatin (10 mg/kg body weight, i.p.). The DMTU+cisplatin group was given DMTU (500 mg/kg body weight, i.p.), just before the cisplatin injection (10 mg/kg body weight, i.p.), followed by injections of DMTU (125 mg/kg body weight, i.p.) twice a day until sacrifice (72 h after the treatment). DMTU did not present any direct effect on mitochondria and substantially inhibited cisplatin-induced mitochondrial damage in liver, therefore preventing elevation of AST and ALT serum levels. DMTU protected against (a) decreased hepatic ATP levels; (b) lipid peroxidation; (c) cardiolipin oxidation; (d) sulfhydryl protein oxidation; (e) mitochondrial membrane rigidification; (f) GSH oxidation; (g) NADPH oxidation; (h) apoptosis. Results suggest that antioxidants, particularly hydroxyl radical scavengers, protect liver mitochondria against cisplatin-induced oxidative damage. Several mitochondrial changes were delineated and proposed as interesting targets for cytoprotective strategy. PMID- 17850779 TI - Differential effects of soybean and fenugreek extracts on the growth of MCF-7 cells. AB - The effect of aqueous and ethanol extracts of soybean and fenugreek on the growth of MCF-7 cells, an estrogen receptor positive breast cancer cell line, has been examined in this study. Soybean is well known for the presence of phytoestrogens and fenugreek is reported to have medicinal use including anticancer properties. In a dose dependent manner soybean aqueous and ethanol extract promoted the growth and DNA synthesis in MCF-7 cells. On the contrary ethanol extract of fenugreek decreased the cell viability and induced early apoptotic changes such as flipping of phosphatidylserine and decrease of mitochondrial membrane potential. Degradation of cellular DNA into fragments comprising multiples of approximately 180-200 base pair was also observed. Cell cycle analysis by flow cytometry showed the presence of a subG1 apoptotic population which was more prominent at higher concentrations along with cell cycle arrest at G2/M phase. Our experiments show that while the soybean extract acts as a promoter of MCF-7 cell growth, the fenugreek extract induces apoptosis. PMID- 17850780 TI - Measurement of serum paraoxonase-1 activity as a potential biomarker for chronic liver impairment. PMID- 17850781 TI - Stable-isotope dilution measurement of isovalerylglycine by tandem mass spectrometry in newborn screening for isovaleric acidemia. AB - BACKGROUND: Recent neonatal screening for isovaleric acidemia by tandem mass spectrometry based on dried blood-spot levels of C5-acylcarnitines, including isovalerylcarnitine and its isomer, pivaloylcarnitine, which is derived from pivalate-generating antibiotics, has caused many false-positive results. We have developed a method to overcome this interference. METHODS: The amounts of isovalerylglycine were determined by a stable-isotope dilution electrospray tandem mass spectrometric analysis, using multiple-reaction monitoring with product ions of m/z 132, which were generated predominantly from quasi-molecular ions of isovalerylglycine butylester but apparently not from those of pivaloylglycine butylester. RESULTS: Isovalerylglycine concentrations in dried blood spots of control newborns were 0.17+/-0.03 nmol/ml, and those of patients with isovaleric acidemia ranged from 1.3 to 80.0 nmol/ml. Those of the newborns treated with antibiotics, which caused high C5-acylcarnitine levels (1.9+/-1.7 nmol/ml) in dried blood spots, were 0.22+/-0.05 nmol/ml. CONCLUSIONS: Our data showed that the present method is useful in eliminating the false-positive results due to antibiotics use in newborn screening for isovaleric acidemia. PMID- 17850783 TI - A G(s)-linked receptor maintains meiotic arrest in mouse oocytes, but luteinizing hormone does not cause meiotic resumption by terminating receptor-G(s) signaling. AB - The maintenance of meiotic prophase arrest in fully grown vertebrate oocytes depends on the activity of a G(s) G-protein that activates adenylyl cyclase and elevates cAMP, and in the mouse oocyte, G(s) is activated by a constitutively active orphan receptor, GPR3. To determine whether the action of luteinizing hormone (LH) on the mouse ovarian follicle causes meiotic resumption by inhibiting GPR3-G(s) signaling, we examined the effect of LH on the localization of Galpha(s). G(s) activation in response to stimulation of an exogenously expressed beta(2)-adrenergic receptor causes Galpha(s) to move from the oocyte plasma membrane into the cytoplasm, whereas G(s) inactivation in response to inhibition of the beta(2)-adrenergic receptor causes Galpha(s) to move back to the plasma membrane. However, LH does not cause a change in Galpha(s) localization, indicating that LH does not act by terminating receptor-G(s) signaling. PMID- 17850782 TI - Nodal signals mediate interactions between the extra-embryonic and embryonic tissues in zebrafish. AB - In many vertebrates, extra-embryonic tissues are important signaling centers that induce and pattern the germ layers. In teleosts, the mechanism by which the extra embryonic yolk syncytial layer (YSL) patterns the embryo is not understood. Although the Nodal-related protein Squint is expressed in the YSL, its role in this tissue is not known. We generated a series of stable transgenic lines with GFP under the control of squint genomic sequences. In all species, nodal-related genes induce their own expression through a positive feedback loop. We show that two tissue specific enhancers in the zebrafish squint gene mediate the response to Nodal signals. Expression in the blastomeres depends upon a conserved Nodal response element (NRE) in the squint first intron, while expression in the extra embryonic enveloping layer (EVL) is mediated by an element upstream of the transcription start site. Targeted depletion experiments demonstrate that the zebrafish Nodal-related proteins Squint and Cyclops are required in the YSL for endoderm and head mesoderm formation. Thus, Nodal signals mediate interactions between embryonic and extra-embryonic tissues in zebrafish that maintain nodal related gene expression in the margin. Our results demonstrate a high degree of functional conservation between the extra-embryonic tissues of mouse and zebrafish. PMID- 17850784 TI - GATA-2 functions downstream of BMPs and CaM KIV in ectodermal cells during primitive hematopoiesis. AB - In Xenopus, primitive blood originates from the mesoderm, but extrinsic signals from the ectoderm are required during gastrulation to enable these cells to differentiate as erythrocytes. The nature of these signals, and how they are transcriptionally regulated, is not well understood. We have previously shown that bone morphogenetic proteins (BMPs) are required to signal to ectodermal cells to generate secondary non-cell-autonomous signal(s) necessary for primitive erythropoiesis, and that calmodulin-dependent protein kinase IV (CaM KIV) antagonizes BMP signaling. The current studies demonstrate that Gata-2 functions downstream of BMP receptor activation in these same cells, and is a direct target for antagonism by CaM KIV. We show, using loss of function analysis in whole embryos and in explants, that ectodermal Gata-2 is required for primitive erythropoiesis, and that BMP signals cannot rescue blood defects caused by ectoderm removal or loss of ectodermal GATA-2. Furthermore, we provide evidence that acetylation of GATA-2 is required for its function in primitive blood formation in vivo. Our data support a model in which Gata-2 is a transcriptional target downstream of BMPs within ectodermal cells, while activation of the CaM KIV signaling pathway alters GATA-2 function posttranslationally, by inhibiting its acetylation. PMID- 17850785 TI - Pharmacological properties of the active metabolites of the antidepressants desipramine and citalopram. AB - Although major metabolites of some antidepressant drugs are known to be active, their pharmacological effects are poorly characterized. Two of the most selective antidepressants, desipramine (selectively inhibits norepinephrine reuptake) and citalopram (selectively inhibits serotonin reuptake) are frequently used in animal studies of antidepressant action, as well as being useful therapeutically. The primary aim of this study was to determine the affinity of desmethyldesipramine, an active metabolite of desipramine, for the rat norepinephrine and serotonin transporters, as well as for the rat alpha(2) adrenoceptor. The pharmacological characteristics of desmethyldesipramine and desmethylcitalopram, an active metabolite of citalopram, were also determined for various human transporters and neurotransmitter receptors. Competition binding studies using [(3)H]nisoxetine and [(3)H]citalopram showed desipramine to be 25 times more selective for the rat norepinephrine as compared to serotonin transporter (6.2 nM vs. 158 nM) whereas desmethyldesipramine is 12 times more selective for the serotonin over the norepinephrine transporter (12.8 nM vs. 153 nM). Interestingly, the affinity of desmethyldesipramine for the serotonin transporter is similar to the affinity of desipramine for the norepinephrine transporter. Desipramine and desmethyldesipramine were found to have a lower affinity for the rat alpha(2A(D))-adrenoceptor than the transporters, suggesting that this receptor is not a major site of action for either compound. Thus, the pharmacological effects of desipramine in rats may be attributed not only to the inhibition of the norepinephrine transporter by desipramine but also to the inhibition of serotonin transporter by the active metabolite desmethyldesipramine. PMID- 17850786 TI - The uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist memantine prolongs spatial memory in a rat delayed radial-arm maze memory task. AB - In the present study, we evaluated the effects of memantine in a delayed radial arm maze rat task, consisting of an acquisition phase followed 18 h later by a win-shift retrieval test. When administered 20 min before acquisition, memantine elicited an inverted U-shape dose-response relationship, with low doses (0.3 and 0.56 mg/kg) reducing the number of errors committed during the retrieval test, while high doses (3 and 10 mg/kg) disrupted maze running. Memantine given immediately after acquisition or 20 min before retrieval failed to affect performance. Co-administration of subthreshold doses of memantine with either the CB(1) receptor antagonist rimonabant or the acetylcholine esterase inhibitor donepezil failed to enhance performance. Thus, low doses of memantine enhance acquisition processes that lead to prolonged spatial memory. PMID- 17850787 TI - Haemostatic imbalance following carrageenan-induced rat paw oedema. AB - Carrageenan-induced rat paw oedema is a widely used model to investigate the physiopathology of an acute local inflammation. Recently, much attention has been focused on the link between haemostasis and inflammation, and on the impact that inflammation might have on thrombotic events. It is known that the systemic response to inflammation is the "acute phase reaction" that represents a highly complex reaction of the organism to a variety of injuries, aimed to restore homeostasis; one important feature of the acute phase reaction is the hepatic synthesis of proteins involved in the coagulation cascade. Much attention has been focused on the role that systemic inflammation might have on thrombotic events, while there is not much information on the role played by an acute local inflammation on haemostasis, that can lead toward a pro-thrombotic state. The present study was conducted to evaluate the haemostatic balance in the early and the late phase of carrageenan-induced rat paw oedema; i.e. at 3 h, when paw inflammation is maximally expressed, and 24 h following carrageenan injection, when there is an almost complete absence of local inflammatory symptoms. We found that in inflamed animals, 24 h following oedema induction, there was an increase in plasma fibrinogen levels, antithrombin III activity and serum interleukin-6 levels, concomitant to a shortened prothrombin time and to an increased platelet responsiveness to ADP. Furthermore, in inflamed tissues at 3 h there was an increase in antithrombin III proteic expression. Our results demonstrate that a haemostatic imbalance occurs following carrageenan-induced rat paw oedema. PMID- 17850788 TI - Taking Rho GTPases to the next level: the cellular functions of atypical Rho GTPases. AB - The Rho GTPases are influential regulators of signalling pathways that control vital cellular processes such as cytoskeletal dynamics, gene transcription, cell cycle progression and cell transformation. A vast majority of the studies involving Rho GTPases have been focused to the famous triad, Cdc42, Rac1 and RhoA, but this protein family actually harbours 20 members. Recently, the less known Rho GTPases have received increased attention. Many of the less studied Rho GTPases have structural, as well as, functional features which makes it pertinent to classify them as atypical Rho GTPases. This review article will focus on the critical aspects of the atypical Rho GTPases, RhoH, Wrch-1, Chp and RhoBTB. These proteins are involved in a broad spectre of biological processes, such as cytoskeletal dynamics, T-cell signalling and protein ubiquitinylation. We will also discuss the roles of atypical Rho GTPases as oncogenes or tumour suppressors, as well as their potential involvement in human diseases. PMID- 17850789 TI - Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCzeta. AB - Prostaglandins are lipid signaling intermediates released by keratinocytes in response to ultraviolet irradiation (UVR) in the skin. The main prostaglandin released following UVR is PGE(2), a ligand for 4 related G-protein-coupled receptors (EP(1), EP(2), EP(3) and EP(4)). Our previous work established that PGE(2) stimulates melanocyte dendrite formation through activation of the EP(1) and EP(3) receptors. The purpose of the present report is to define the signaling intermediates involved in EP(1)- and EP(3)-dependent dendrite formation in human melanocytes. We recently showed that activation of the atypical PKCzeta isoform stimulates melanocyte dendricity in response to treatment with lysophosphatidylcholine. We therefore examined the potential contribution of PKCzeta activation on EP(1)- and EP(3)-dependent dendrite formation in melanocytes. Stimulation of the EP(1) and EP(3) receptors by selective agonists activated PKCzeta, and inhibition of PKCzeta activation abrogated EP(1)- and EP(3)-receptor-mediated melanocyte dendricity. Because of the importance of Rho GTP binding proteins in the regulation of melanocyte dendricity, we also examined the effect of EP(1) and EP(3) receptor activation on Rac and Rho activity. Neither Rac nor Rho was activated upon treatment with EP(1,3)-receptor agonists. We show that melanocytes express only the EP(3A1) isoform, but not the EP(3B) receptor isoform, previously associated with Rho activation, consistent with a lack of Rho stimulation by EP(3) agonists. Our data suggest that PKCzeta activation plays a predominant role in regulation of PGE(2)-dependent melanocyte dendricity. PMID- 17850790 TI - Establishment of an appropriate animal model for lacritin studies: cloning and characterization of lacritin in monkey eyes. AB - Lacritin is a mitogen of human salivary gland cells as well as a stimulator of human corneal epithelial cells. It is expected to be an important factor in maintaining the surrounding ocular surface. The monkey would be a relevant animal model in which to study the role of lacritin in ophthalmic physiology and pathology. However, to our knowledge, no cDNA cloning or functional analysis of monkey lacritin has been performed. Thus, the purposes of this study were: (1) to clone the monkey ortholog of lacritin; (2) to characterize lacritin in tears from several species; and (3) to determine the tissues where lacritin is produced and secreted. cDNA for lacritin from rhesus macaque contained 547 bp, with 411 bp in an open reading frame (ORF) encoding a protein of 137 amino acids. Monkey lacritin showed 89% amino acid homology with human lacritin; one amino acid was deleted in all three monkey strains. The predicted MW of mature lacritin was 12.2 kDa, and the isoelectric point was 4.99. Lacritin showed anomalous migration at approximately 21.0 kDa on SDS-PAGE, as confirmed by immunoblotting and amino acid sequencing. Similar to native lacritin in monkey tears, a 21 kDa band was also detected in human tears. In contrast, no lacritin was observed at a similar position on SDS-PAGE in rat, rabbit and dog tears. In the monkey, lacritin mRNA was expressed highly in the lacrimal gland, moderately in the conjunctiva and the meibomian gland, and weakly in corneal epithelium. In primates, lacritin was produced in the lacrimal gland and secreted into tear fluid. These results suggest that lacritin might be important for the maintenance of the ocular surface in higher animals, such as monkeys and humans. PMID- 17850791 TI - Epidural stimulation: comparison of the spinal circuits that generate and control locomotion in rats, cats and humans. AB - Although epidural stimulation is a technique that has been used for a number of years to treat individuals with a spinal cord injury, the intended outcome has been to suppress plasticity and pain. Over the last decade considerable progress has been made in realizing the potential of epidural stimulation to facilitate posture and locomotion in subjects with severe spinal cord injury who lack the ability to stand or to step. This progress has resulted primarily from experiments with mice, rats and cats having a complete spinal cord transection at a mid-thoracic level and in humans with a complete spinal cord injury. This review describes some of these experiments performed after the complete elimination of supraspinal input that demonstrates that the circuitry necessary to control remarkably normal locomotion appears to reside within the lumbosacral region of the spinal cord. These experiments, however, also demonstrate the essential role of processing proprioceptive information associated with weight bearing stepping or standing by the spinal circuitry. For example, relatively simple tonic signals provided to the dorsum of the spinal cord epidurally can result in complex and highly adaptive locomotor patterns. Experiments emphasizing a significant complementary effect of epidural stimulation when combined with pharmacological facilitation, e.g., serotonergic agonists, and/or chronic step training also are described. Finally, a major point emphasized in this review is the striking similarity of the lumbosacral circuitry controlling locomotion in the rat and in the human. PMID- 17850792 TI - Trypanosoma brucei gambiense: study of population genetic structure of Central African stocks using amplified fragment length polymorphism (AFLP). AB - To understand the maintenance and resurgence of historical Human African Trypanosomiasis (HAT) foci, AFLP was used to genotype 100 Central African Trypanosoma brucei s.l. stocks. This technique confirmed the high genetic stability of T. b. gambiense group 1 stocks and the micro genetic variability within Central African T. b. gambiense stocks. It revealed several T. b. gambiense genotypes and allowed the identification of minor and major genotypes in HAT foci. The coexistence of these genotypes in the same focus suggests that clustering of stocks according to HAT focus does not provide the true genetic picture of trypanosome circulating within the disease focus because the minor genotypes are generally underestimated. The presence of minor and major genotypes in HAT foci may explain the persistence and the resurgence of Central African sleeping sickness foci. PMID- 17850793 TI - Eye-open at birth phenotype with reduced keratinocyte motility in LGR4 null mice. AB - We observed a consistent eye-open at birth (EOB) phenotype in mouse pups homozygous for a leucine-rich repeat containing G-protein coupled receptor 4 (Lgr4) allele deleting the whole transmembrane domain coding region. An in vitro wound-healing scratch assay showed notably reduced keratinocyte motility in the null mice. Phalloidin staining of F-actin in the eyelid epidermis was also reduced. We also generated keratinocyte-specific Lgr4 deficient mice, circumventing the embryonic/neonatal lethality and kidney abnormalities. Most of the conditional Lgr4 knockout mice showed the EOB phenotype. Thus, Lgr4 might be a novel gene class regulating cell motility. PMID- 17850794 TI - VEGF receptor Flk-1 plays an important role in c-kit expression in adipose tissue derived stem cells. AB - It is known that c-kit(+) cells are increased in heart after infarction. The exact origins of the cardiac c-kit(+) cells remain to be determined. We asked whether adipose tissue could be a potential source of c-kit(+) cells. Our data show that the number of c-kit(+) cells increased in adipose tissue derived stem cells when cultured with conditioned medium from neonatal cardiomyocytes grown under serum deprivation and hypoxia condition. We also found that VEGF receptor Flk-1 is involved in c-kit up regulation via ERK-mediated pathway. PMID- 17850795 TI - Homocysteine-induced endothelial cell adhesion is related to adenosine lowering and is not mediated by S-adenosylhomocysteine. AB - Hyperhomocysteinemia is a cardiovascular risk factor and may contribute to the pathogenesis of atherosclerosis by altering endothelial functions. The mechanism of homocysteine-induced cell adhesion has been here investigated using EA.hy 926 cells. Homocysteine induces a stereospecific, time- and dose-dependent cell adhesion which is prevented by adenosine. The dramatic increase of S adenosylhomocysteine induced by adenosine-2',3'-dialdehyde does not cause cell adhesion, indicating that no apparent relationship exists between this process and intracellular S-adenosylhomocysteine content. Homocysteine-induced cell adhesion is abolished by pre-treatment with adenosine-2',3'-dialdehyde, demonstrating that the adenosine depletion caused by reversal of S adenosylhomocysteine hydrolase reaction is responsible for homocysteine-induced cell damage. PMID- 17850796 TI - PrrC, a Sco homologue from Rhodobacter sphaeroides, possesses thiol-disulfide oxidoreductase activity. AB - PrrC is a Sco homologue in Rhodobacter sphaeroides that is associated with PrrBA, a two-component signal transduction system that induces photosynthesis gene expression in response to a decrease in oxygen tension. Although Sco proteins have been shown to bind copper the observation that they are structurally-related to thioredoxins suggested that they might possess thiol-disulfide oxidoreductase activity. Our results show that PrrC reduces Cu(2+) to Cu(+) and possesses disulfide reductase activity. These results indicate that some bacterial Sco proteins may have biochemical properties that are distinct from those of mitochondrial Sco proteins. PMID- 17850797 TI - A specific binding site for neoxanthin in the monomeric antenna proteins CP26 and CP29 of Photosystem II. AB - The location of the neoxanthin binding site in CP26 and CP29 was investigated by site-directed mutagenesis. The crystallographic structure of LHCII shows that the binding of neoxanthin to the N1 site is stabilised by an H bond with a tyrosine in the lumenal loop. This residue is conserved in CP26 and CP29. Mutation of this tyrosine into phenylalanine induced specific loss of neoxanthin without affecting violaxanthin binding. In contrast to previous proposals, it is thus concluded that also in these minor antenna complexes neoxanthin is accommodated in the N1 site. The characteristics of this binding site in the different antenna complexes are discussed. PMID- 17850798 TI - Pituitary and placental ovine growth hormone variants differ in their receptor binding ability and in their biological properties. AB - The wild-type (WT) GH2-N ovine growth hormone (oGH) and duplicated GH2-Z genes differ in their open reading frame by two nonsynonymous substitutions, predicting a two-amino-acid difference in their product (G9R/G63S). Three recombinant oGH muteins: G9R, G63S and G9R/G63S, were prepared by site-directed mutagenesis of the WT oGH gene, expressed in E. coli, refolded and purified as monomers with over 98% homogeneity. Gel-filtration experiments with WT oGH and the three muteins indicated formation of 1:2 complexes with oGH receptor extracellular domain (oGHR-ECD). Interactions of oGHR-ECD with the WT and the muteins were studied by surface plasmon resonance. Kinetics constants calculated using a two site model predicted that G9R/G63S has the highest affinity to oGHR-ECD, WT oGH the lowest, and G9R and G63S have intermediate affinities. These relative affinities were further investigated by radioreceptor assay with EC50 values were the lowest for G9R/G63S, highest for WT oGH, and intermediate for G9R and G63S. Bioactivity of the WT oGH and oGH muteins was determined by proliferation assay with FDC-P1-3B9 cells stably transfected with rabbit GHR. Relative proliferation rates of cells in cultures treated with the WT, G63S, G9R or G9R/G63S variants were 100%, 183%, 259% and 498%, respectively. In COS-7 transfected with oGHR, LHRE-TK-luciferase and beta-galactosidase plasmids G9R/G63S showed 18% higher activity than WT oGH (P<0.001). Thus the product of the oGH duplicated copy has higher affinity for GHR and higher somatogenic activity. As the GH2-Z gene copy is expressed in the placenta, allelic differences at the oGH locus may influence feto-placental development. PMID- 17850799 TI - Experimental dynamic characterizations and modelling of disk vibrations for HDDs. AB - Currently, the rotational speed of spindle motors in HDDs (Hard-Disk Drives) are increasing to improve high data throughput and decrease rotational latency for ultra-high data transfer rates. However, the disk platters are excited to vibrate at their natural frequencies due to higher air-flow excitation as well as eccentricities and imbalances in the disk-spindle assembly. These factors contribute directly to TMR (Track Mis-Registration) which limits achievable high recording density essential for future mobile HDDs. In this paper, the natural mode shapes of an annular disk mounted on a spindle motor used in current HDDs are characterized using FEM (Finite Element Methods) analysis and verified with SLDV (Scanning Laser Doppler Vibrometer) measurements. The identified vibration frequencies and amplitudes of the disk ODS (Operating Deflection Shapes) at corresponding disk mode shapes are modelled as repeatable disturbance components for servo compensation in HDDs. Our experimental results show that the SLDV measurements are accurate in capturing static disk mode shapes without the need for intricate air-flow aero-elastic models, and the proposed disk ODS vibration model correlates well with experimental measurements from a LDV. PMID- 17850800 TI - Validity of the ATP III diagnostic criteria for the metabolic syndrome in an elderly Italian Caucasian population: the Italian Longitudinal Study on Aging. AB - The metabolic syndrome (MetS) is represented by the co-occurrence of multiple metabolic and physiologic risk factors for both type 2 diabetes mellitus and atherosclerotic cardiovascular diseases. In spite of its high frequency and association with morbidity and mortality in the adult population, very little is known about its magnitude in the elderly and about the validity of the diagnostic criteria commonly used. The objective of this paper is to assess the prevalence rate of MetS and the validity of the Adult Treatment Panel III (ATP III) diagnostic criteria in an elderly Caucasian cohort, considering data from the Italian Longitudinal Study on Aging (ILSA), a population-based study with a sample of 5632 individuals aged 65-84 years at baseline (1992). Logistic regression models and ROC curve were used to test the validity of the cut off levels proposed. The prevalence of MetS was 31.5% in men, and 59.8% in women. The cut off levels suggested for both men and women by the ATP III panel indicated a significant association with the MetS for all components. Actually, the ROC analysis would suggest lower levels for glycaemia (106 mg/dl) in men, and higher levels for blood pressure in both men and women (145/95 and 135/90, respectively). Concluding, MetS is very common in the aged Caucasians and the diagnostic criteria proposed by the ATP III panel seem to be appropriate in older individuals. Small adjustments in the cut off levels could be suggested for glycaemia (men) and in blood pressure (men and women). PMID- 17850801 TI - Pigment epithelium-derived factor (PEDF) administration inhibits occlusive thrombus formation in rats: a possible participation of reduced intraplatelet PEDF in thrombosis of acute coronary syndromes. AB - OBJECTIVES: Although remarkable therapeutic advances in the treatment of acute coronary syndromes (ACS) have been made with anti-platelet therapy, the therapeutic options may be limited by considerable side effects. Pigment epithelium-derived factor (PEDF) has anti-oxidative properties and may play a protective role against atherosclerosis. In this study, we investigated whether PEDF prevented occlusive thrombus formation in rats. METHODS AND RESULTS: Occlusive thrombus formation was induced by treating rats with ligation and cuff placement at the left common carotid artery. Intravenous injection of PEDF dose dependently inhibited thrombus formation and blocked the increase in immunoreactivity of P-selectin, a marker of platelet activation, NADPH oxidase activity and superoxide generation in thrombi. In vitro, PEDF significantly decreased collagen-induced reactive oxygen species generation in platelets and subsequently suppressed the platelet activation and aggregation. Plasma and intraplatelet levels of PEDF in the coronary circulation in patients with ACS were significantly lower than those in age- and gender-matched controls without coronary artery disease. CONCLUSIONS: These results demonstrated that PEDF administration could inhibit occlusive thrombus formation by blocking the platelet activation and aggregation through its anti-oxidative properties. Our present study suggests that pharmacological up-regulation or substitution of PEDF may offer a promising strategy for the treatment of arterial thrombosis. PMID- 17850802 TI - Surfactant coated fullerenes C60 as pseudostationary phase in electrokinetic chromatography. AB - In the present paper, surfactant coated fullerenes C(60) (SC-C(60)) have been proposed as a novedous pseudostationary phase to improve separation of different aromatic compounds. The target analytes were beta-lactams antibiotics, non steroidal anti-inflammatory drugs and amphenicols. In all cases, the analytes interacted with the pseudostationary phase producing an important enhancement on resolution. The results were compared with those obtained with surfactant coated carbon nanotubes (single-walled and multi-walled nanotubes), showing that in the proposed conditions, fullerenes C(60) were advantageous as interactions between the analytes and the pseudostationary phase were more effective. Finally, the procedure was applied to pharmaceuticals and urine samples, with satisfactory results. PMID- 17850803 TI - Ice chromatography modification of solute retention on water-ice stationary phase. AB - Ice chromatography, in which water-ice particles are used as the stationary phase, has high potential as a separation tool, and is an efficient approach to probe the molecular interaction occurring on the water-ice surface. In the present paper, to modify solute retention, several methods are proposed, that is, changing the mobile phase composition, the surface modification of water-ice, and the implantation of functional molecules into water-ice. The retention mechanism of ice chromatography is discussed through these retention modifications. PMID- 17850804 TI - Trace analysis of impurities in bulk gases by gas chromatography-pulsed discharge helium ionization detection with "heart-cutting" technique. AB - A method has been developed for the detection of low-nL/L-level impurities in bulk gases such as H(2), O(2), Ar, N(2), He, methane, ethylene and propylene, respectively. The solution presented here is based upon gas chromatography-pulsed discharge helium ionization detection (GC-PDHID) coupled with three two-position valves, one two-way solenoid valve and four packed columns. During the operation, the moisture and heavy compounds are first back-flushed via a pre-column. Then the trace impurities (except CO(2) which is diverted to a separate analytical column for separation and detection) together with the matrix enter onto a main column, followed by the heart-cut of the impurities onto a longer analytical column for complete separation. Finally the detection is performed by PDHID. This method has been applied to different bulk gases and the applicability of detecting impurities in H(2), Ar, and N(2) are herewith demonstrated. As an example, the resulting detection limit of 100 nL/L and a dynamic range of 100 1000 nL/L have been obtained using an Ar sample containing methane. PMID- 17850805 TI - A high-efficiency capillary electrophoresis-based method for characterizing the sizes of Au nanoparticles. AB - In this paper, we present a highly efficient capillary electrophoresis (CE)-based method for characterizing the sizes of Au nanoparticles (NPs). We used the reversed electrode polarity stacking mode (REPSM) of CE for on-line enhancement of the detection and separation of Au NPs. Under the on-line enhancement separation conditions [buffer: SDS (70 mM) and 3-cyclohexylamino-1 propanesulfonic acid (10 mM) at pH 10.0; applied voltage: 20 kV; using the REPSM for sample concentration], the detection sensitivity toward the Au NPs improved by up to 260-fold. A linear relationship (R(2)=0.994) existed between the electrophoretic mobilities and the sizes of the Au NPs within the range of diameters from 5.3 to 59.9 nm; the relative standard deviations of the electrophoretic mobilities for these NPs were below 0.6%. When using these conditions to analyze Au NPs produced through seed-assisted synthesis, a good correlation existed between the sizes obtained using CE and those provided by transmission electron microscopy. Furthermore, the analyses performed using CE were rapid (<4 min) and required very low sample volumes (several nanoliters), yet they proceeded with high sensitivity. These findings confirm that CE is an efficient tool for characterizing the sizes of NPs. PMID- 17850806 TI - Trilinear decomposition method applied to removal of three-dimensional background drift in comprehensive two-dimensional separation data. AB - A novel technique for removal of three-dimensional background drift in comprehensive two-dimensional (2D) liquid chromatography coupled with diode array detection (LCxLC-DAD) data is proposed. The basic idea is to perform trilinear decomposition on the instrumental response data, which is based on the alternating trilinear decomposition (ATLD) algorithm. In model construction, the background drift is modeled as one component or factor as well as the analytes of interest, hence, the drift is explicitly included into the calibration. The method involves performing trilinear decomposition on the raw data, then extracting the background component and subtracting this background data from the raw data, leaving the analytes' signal on a flat baseline. Simultaneous evaluation of three-dimensional background drift and true signals may improve the quality of the data. This method is applied to the determination and removal of three-dimensional background drifts in simulated multidimensional data as well as experimental comprehensive two-dimensional liquid chromatographic data. It is shown that this technique yield a good removal of background drift, without the need to perform a blank chromatographic run, and required no prior knowledge about the sample composition. PMID- 17850807 TI - Simulation of flux during electro-membrane extraction based on the Nernst-Planck equation. AB - The present work has for the first time described and verified a theoretical model of the analytical extraction process electro-membrane extraction (EME), where target analytes are extracted from an aqueous sample, through a thin layer of 2-nitrophenyl octylether immobilized as a supported liquid membrane (SLM) in the pores in the wall of a porous hollow fibre, and into an acceptor solution present inside the lumen of the hollow fibre by the application of an electrical potential difference. The mathematical model was based on the Nernst-Planck equation, and described the flux over the SLM. The model demonstrated that the magnitude of the electrical potential difference, the ion balance of the system, and the absolute temperature influenced the flux of analyte across the SLM. These conclusions were verified by experimental data with five basic drugs. The flux was strongly dependent of the potential difference over the SLM, and increased potential difference resulted in an increase in the flux. The ion balance, defined as the sum of ions in the donor solution divided by the sum of ions in the acceptor solution, was shown to influence the flux, and high ionic concentration in the acceptor solution relative to the sample solution was advantageous for high flux. Different temperatures also led to changes in the flux in the EME system. PMID- 17850808 TI - Quantitative determination of 4-ethylphenol and 4-ethyl-2-methoxyphenol in wines by a stable isotope dilution assay. AB - The deuterium-labelled standards 4-ethylphenol-d(3) and 4-ethyl-2-methoxyphenol d(3) were synthesized and utilized in a rapid, sensitive, and accurate stable isotope dilution assay for 4-ethylphenol and 4-ethyl-2-methoxyphenol in wine. For a 5-mL sample of a Merlot wine, quantitation was reliable down to 500 ng/L for 4 ethylphenol and 100 ng/L for 4-ethyl-2-methoxyphenol at estimated signal-to-noise ratio of 3:1, respectively. The concentrations of 4-ethylphenol and 4-ethyl-2 methoxyphenol were also measured in 54-barrelled red commercial wines from the Okanagan Valley in British Columbia. The results indicate significantly different internal standard recoveries for the two analytes, demonstrating the need for individual stable isotope derivatives to reliably quantitate 4-ethylphenol and 4 ethyl-2-methoxyphenol in wines. PMID- 17850809 TI - Simultaneous quantification of sulfamethoxazole and trimethoprim in whole egg samples by column-switching high-performance liquid chromatography using restricted access media column for on-line sample clean-up. AB - This work reports the application of restricted access media (RAM) column, in a multidimensional configuration, for simultaneous analysis of sulfamethoxazole (SMX) and trimethoprim (TMP) in whole eggs with ultraviolet detection. The proteins were partially precipitated by adding 0.5 mL of acetonitrile into 1.0 mL of blended egg followed by centrifugation. The supernatant was injected (250 microL) directly into the multidimensional system. At the first dimension, a restricted access medium (RAM) bovine serum albumin (BSA) octadecyl column (100 mm x 46 mm I.D., Luna silica, 10 microm particle size and 100 A pore size), was used for extraction and concentration of the analytes and at second dimension, an octadecyl column (150 mm x 46 mm I.D., Luna silica, 10 microm particle size and 100 A pore size), for analysis. The developed method showed good selectivity, accuracy and precision for quantification of these different compounds in eggs, and the limits of quantification were 80 ng/mL, for both compounds. The validated method is reliable and sensitive for monitoring residues in whole eggs samples and thus, to determine withdraw period for laying hens using veterinary medicine having SMX-TMP combination. PMID- 17850810 TI - Using supercritical fluid chromatography to determine diffusion coefficients of 1,2-diethylbenzene, 1,4-diethylbenzene, 5-tert-butyl-m-xylene and phenylacetylene in supercritical carbon dioxide. AB - The binary diffusion of 1,2-diethylbenzene, 1,4-diethylbenzene, 5-tert-butyl-m xylene and phenylacetylene at infinite dilution in supercritical carbon dioxide were measured between 15.0 and 35.0 MPa and in the temperature range of 313.16 to 333.16K by the Taylor-Aris chromatographic method. The effect of temperature, pressure, viscosity and density was discussed. In the case of temperature dependence, additional measurements were done for 5-tert-butyl-m-xylene from 308.16 to 398.16K at 35.0 MPa. The measured diffusivities of the four solutes were compared with the calculated ones by several predictive formulas. PMID- 17850811 TI - Interaction of colloidal particles of NH(4)(+)-montmorillonite with activated carbon. AB - The interaction between negative colloidal particles of NH(4)(+)-montmorillonite and particles of activated carbon was studied as a function of particle concentration, pH, and time of contact. The results show that carbon particles act as a support/bridge for clay particles, the type of resulting clay/carbon/clay associations depending on the pH and the clay/carbon ratio in the system. The relation between clay and carbon particles can be described by equations of the Langmuir type. For the same carbon particle concentration in the system, the relation varies from 6820 to 36,100 and is dependent on pH. The interaction coefficients at pH 6.5 correspond to reaction of pseudo-first (k(1)=4.14 x 10(-3) to 1.93 x 10(-3) s(-1)) and pseudo-second order (k(2)=9.36 x 10(-14) to 2.47 x 10(-14) cm(3)s(-1)) for different clay/carbon ratios. By using the Dubinin-Radushkevich equation, the interaction energy (+/-22.42, +/-685.0, and +/-14.63 J mol(-1)) was obtained for three different pH values (5, 6.7, and 7.6), demonstrating that the reaction is mainly physical. PMID- 17850812 TI - Synthesis and characterization of CdSe nanorods using a novel microemulsion method at moderate temperature. AB - CdSe nanoparticles have been successfully synthesized using a novel microemulsion method at moderate temperature. It is found that with a combination of the surfactant AOT and hydrazine hydrate, it is possible to control the morphology of the nanoparticles. The hydrazine hydrate acts as both a reducing agent and a templating agent that favors the formation of a rodlike structure. The composition, morphology and optical properties of the CdSe nanoparticles were investigated using powder X-ray diffraction (XRD), transmission electron microscopy (TEM), ultraviolet-visible (UV-vis) absorption spectroscopy, photoluminescence (PL) spectroscopy, energy dispersive X-ray spectroscopy (EDX) and Fourier transform infrared (FT-IR) spectroscopy. The nucleation and growth mechanism for this system is also proposed based on a time-dependent study. This synthesis route provides a moderate temperature (100 degrees C) method for synthesizing rodlike CdSe, hence reducing the possibility of oxidation of this chalcogenide compound. PMID- 17850813 TI - Effect of friction between particles in the dynamic response of model magnetic structures. AB - A simple particle-level simulation model that takes into account interparticle friction forces is developed to describe the dynamic response of magneto rheological fluids. The results obtained for single-width particle chains are found to be in good agreement with slender body theory predictions [J. de Vicente, M.T. Lopez-Lopez, J.D.G. Duran, G. Bossis, J. Colloid Interface Sci. 282 (2005) 193]. The addition of side chains to a single-width one results in one order of magnitude increase of storage modulus and relaxation. The double logarithmic plot of storage and loss moduli vs frequency gives a limiting slope of one when including friction forces between particles. Simulation results are found to be in agreement with experimental measurements on an iron/kerosene model MR-fluid. PMID- 17850814 TI - ArgR-dependent repression of arginine and histidine transport genes in Escherichia coli K-12. AB - In Escherichia coli L-arginine is taken up by three periplasmic binding protein dependent transport systems that are encoded by two genetic loci: the artPIQM artJ and argT-hisJQMP gene clusters. The transcription of the artJ, artPIQM and hisJQMP genes and operons is repressed by liganded ArgR, whereas argT, encoding the LAO (lysine, arginine, ornithine) periplasmic binding protein, is insensitive to the repressor. Here we characterize the repressible Esigma70 P artJ, P artP and P hisJ promoters and demonstrate that the cognate operators consist of two 18 bp ARG boxes separated by 3 bp. Determination of the energy landscape of the ArgR operator contacts by missing contact probing and mutant studies indicated that each box of a pair contributes to complex formation in vitro and to the repressibility in vivo, but to a different extent. The organization of the ARG boxes and promoter elements in the control regions of the uptake genes is distinct from that of the arginine biosynthetic genes. The hisJQMP operon is the first member of the E. coli ArgR regulon, directly repressed by liganded ArgR, where none of the core promoter elements overlaps the ARG boxes. Single round in vitro transcription assays and DNase I footprinting experiments indicate that liganded ArgR inhibits P artJ and P artP promoter activity by steric exclusion of the RNA polymerase. In contrast, ArgR-mediated repression of P hisJ by inhibition of RNA polymerase binding appears to occur through topological changes of the promoter region. PMID- 17850815 TI - The crystal structure of human E-cadherin domains 1 and 2, and comparison with other cadherins in the context of adhesion mechanism. AB - Cell adhesion mediated by type I cadherins involves homophilic "trans" interactions that are thought to be brought about by a strand exchange mechanism involving the N-terminal extracellular domain. Here, we present the high resolution crystal structure of the N-terminal two domains of human E-cadherin. Comparison of this structure with other type I cadherin structures reveals features that are likely to be critical to facilitate dimerization by strand exchange as well as dimer flexibility. We integrate this structural knowledge to provide a model for type I cadherin adhesive interactions. Intra-molecular docking of the conserved N-terminal "adhesion arm" into the acceptor pocket in monomeric E-cadherin appears largely identical to inter-molecular docking of the adhesion arm in adhesive trans dimers. A strained conformation of the adhesion arm in the monomer, however, may create an equilibrium between "open" and "closed" forms that primes the cadherin for formation of adhesive interactions, which are then stabilized by additional dimer-specific contacts. By contrast, in type II cadherins, strain in the adhesion arm appears absent and a much larger surface area is involved in trans adhesion, which may compensate the activation energy required to peel off the intra-molecularly docked arm. It seems that evolution has selected slightly different adhesion mechanisms for type I and type II cadherins. PMID- 17850816 TI - Substrate-induced conformational changes and dynamics of UDP-N acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase-2. AB - O-Glycan biosynthesis is initiated by the transfer of N-acetylgalactosamine (GalNAc) from a nucleotide sugar donor (UDP-GalNAc) to Ser/Thr residues of an acceptor substrate. The detailed transfer mechanism, catalyzed by the UDP-GalNAc polypeptide:N-acetyl-alpha-galactosaminyltransferases (ppGalNAcTs), remains unclear despite structural information available for several isoforms in complex with substrates at various stages along the catalytic pathway. We used all-atom molecular dynamics simulations with explicit solvent and counterions to study the conformational dynamics of ppGalNAcT-2 in several enzymatic states along the catalytic pathway. ppGalNAcT-2 is simulated both in the presence and in the absence of substrates and reaction products to examine the role of conformational changes in ligand binding. In multiple 40-ns-long simulations of more than 600 ns total run time, we studied systems ranging from 45,000 to 95,000 atoms. Our simulations accurately identified dynamically active regions of the protein, as previously revealed by the X-ray structures, and permitted a detailed, atomistic description of the conformational changes of loops near the active site and the characterization of the ensemble of structures adopted by the transferase complex on the transition pathway between the ligand-bound and ligand-free states. In particular, the conformational transition of a functional loop adjacent to the active site from closed (active) to open (inactive) is correlated with the rotameric state of the conserved residue W331. Analysis of water dynamics in the active site revealed that internal water molecules have an important role in enhancing the enzyme flexibility. We also found evidence that charged side chains in the active site rearrange during site opening to facilitate ligand binding. Our results are consistent with the single-displacement transfer mechanism previously proposed for ppGalNAcTs based on X-ray structures and mutagenesis data and provide new evidence for possible functional roles of certain amino acids conserved across several isoforms. PMID- 17850817 TI - Episomally driven antisense mRNA abrogates the hyperinducible expression and function of a unique cell surface class I nuclease in the primitive trypanosomatid parasite, Crithidia luciliae. AB - Here, we show that Crithidia luciliae, a primitive trypanosomatid, purine auxotroph, up-expressed its unique, bi-functional, surface membrane 3' nucleotidase/nuclease (Cl 3'NT/NU) activity by approximately 1000-fold in response to purine starvation. A second surface membrane phospho-monoesterase, i.e. a tartrate-resistant acid phosphatase (Cl MAcP) was also found to be up expressed in such purine-starved cells. Here, we used homologous episomal expression of an antisense construct of the Cl3'NT/NU to dissect the functional expression of these two surface membrane enzymes. In antisense transfected cells, a large excess of the antisense transcript was produced and no trace of any endogenous Cl3'NT/NU sense message was detected. Further, the purine-starvation hyper-induced levels of 3'NT/NU enzyme activity were completely abrogated in these transfected cells versus controls. Moreover, such antisense transcription completely abolished the ability of these transfectants to grow in poly(A) containing medium demonstrating the essential nature of the 3'NT/NU for the growth/survival of this parasite. In contrast, antisense transcription had no apparent deleterious effects on either endogenous or purine-starvation-induced levels of MAcP enzyme activity, its steady-state mRNA levels, or the constitutive expression of house-keeping genes (e.g. Cl alpha-tubulin) in these transfectants. Cumulatively, results of our antisense experiments demonstrated that the functional nuclease activity of the surface membrane Cl 3'NT/NU was, in fact, critical/essential for the growth and development of these primitive parasites. PMID- 17850818 TI - Molecular mechanism of the redox-dependent interaction between NADH-dependent ferredoxin reductase and Rieske-type [2Fe-2S] ferredoxin. AB - The electron transfer system of the biphenyl dioxygenase BphA, which is derived from Acidovorax sp. (formally Pseudomonas sp.) strain KKS102, is composed of an FAD-containing NADH-ferredoxin reductase (BphA4) and a Rieske-type [2Fe-2S] ferredoxin (BphA3). Biochemical studies have suggested that the whole electron transfer process from NADH to BphA3 comprises three consecutive elementary electron-transfer reactions, in which BphA3 and BphA4 interact transiently in a redox-dependent manner. Initially, BphA4 receives two electrons from NADH. The reduced BphA4 then delivers one electron each to the [2Fe-2S] cluster of the two BphA3 molecules through redox-dependent transient interactions. The reduced BphA3 transports the electron to BphA1A2, a terminal oxygenase, to support the activation of dioxygen for biphenyl dihydroxylation. In order to elucidate the molecular mechanisms of the sequential reaction and the redox-dependent interaction between BphA3 and BphA4, we determined the crystal structures of the productive BphA3-BphA4 complex, and of free BphA3 and BphA4 in all the redox states occurring in the catalytic cycle. The crystal structures of these reaction intermediates demonstrated that each elementary electron transfer induces a series of redox-dependent conformational changes in BphA3 and BphA4, which regulate the interaction between them. In addition, the conformational changes induced by the preceding electron transfer seem to induce the next electron transfer. The interplay of electron transfer and induced conformational changes seems to be critical to the sequential electron-transfer reaction from NADH to BphA3. PMID- 17850819 TI - Solvation and desolvation dynamics in apomyoglobin folding monitored by time resolved infrared spectroscopy. AB - Solvation and desolvation dynamics around helices during the kinetic folding process of apomyoglobin (apoMb) were investigated by using time-resolved infrared (IR) spectroscopy based on continuous-flow rapid mixing devices and an IR microscope. The folding of apoMb can be described by the collapse and search mechanism, in which the initial collapse occurring within several hundreds of microseconds is followed by the search for the correct secondary and tertiary structures. The time-resolved IR measurements showed a significant increase in solvated helix possessing a component of amide I' at 1633 cm(-1) within 100 mus after initiating the folding by a pD jump from pD2.2 to 6.0. In contrast, there was a minor increase in buried helices having amide I' at 1652 cm(-1) in this time domain. The observations demonstrate that the initially collapsed conformation of apoMb possesses a large amount of solvated helices, and suggest that much water is retained inside the collapsed domain. The contents of solvated and buried helices decrease and increase, respectively, in the time domain after the collapse, showing that the stepwise desolvation around helices is associated with the conformational search process. Interestingly, the largest changes in solvated and buried helices were observed at the final rate-limiting step of the apoMb folding. The persistence of the solvated helix until the final stage of apoMb folding suggests that the dissociation of hydrogen bonds between water and main-chain amides contributes to the energy barrier in the rate-determining step of the folding. PMID- 17850820 TI - Protein folding kinetics provides a context-independent assessment of beta-strand propensity in the Fyn SH3 domain. AB - Structural database-derived propensities for amino acids to adopt particular local protein structures, such as alpha-helix and beta-strand, have long been recognized and effectively exploited for the prediction of protein secondary structure. However, the experimental verification of database-derived propensities using mutagenesis studies has been problematic, especially for beta strand propensities, because local structural preferences are often confounded by non-local interactions arising from formation of the native tertiary structure. Thus, the overall thermodynamic stability of a protein is not always altered in a predictable manner by changes in local structural propensity at a single position. In this study, we have undertaken an investigation of the relationship between beta-strand propensity and protein folding kinetics. By characterizing the effects of a wide variety of amino acid substitutions at two different beta strand positions in an SH3 domain, we have found that the observed changes in protein folding rates are very well correlated to beta-strand propensities for almost all of the substitutions examined. In contrast, there is little correlation between propensities and unfolding rates. These data indicate that beta-strand conformation is well formed in the structured portion of the SH3 domain transition state, and that local structure propensity strongly influences the stability of the transition state. Since the transition state is known to be packed more loosely than the native state and likely lacks many of the non-local stabilizing interactions seen in the native state, we suggest that folding kinetics studies may generally provide an effective means for the experimental validation of database-derived local structural propensities. PMID- 17850821 TI - Neuro-Behcet's disease mimicking multiple brain tumors: diffusion-weighted MR study and literature review. AB - A 47-year-old man with Behcet's disease presented with a five day history of right side weakness and dysarthria. Ten years ago, he was diagnosed as Behcet's disease. Since then, he was treated with low dose steroids. T1-weighted magnetic resonance images with gadolinium injection revealed ring enhancing lesions with internal hypointensities at the left side of the pons and at the left parietal cortex suggesting multiple metastatic tumors. Diffusion-weighted image and ADC map revealed central hyperintensity on diffusion with low ADC values at both lesions. The histopathology of stereotactic biopsy specimen showed frequent perivascular lymphocytic cuffings, focal necrotic lesions and reactive gliosis. The most common neuropathologic findings in neuro-Behcet's disease are focal necrotic lesions, but the location in cerebral cortex has not been reported before. Long term steroid therapy and antibiotics were administered and the patient recovered gradually. Neuro-Behcet's disease could be presented as brain tumor like lesion, and stereotactic biopsy should be considered in such situation. PMID- 17850822 TI - Peripheral and central neurologic complications in type 2 diabetes mellitus: no association in individual patients. AB - Diabetes mellitus is associated with end-organ complications in the peripheral and central nervous system. It is unknown if these complications share a common aetiology, and if they co-occur in the same patient. The aim of the present study was to relate different measures of peripheral neuropathy in patients with type 2 diabetes mellitus (DM2) to cognition and brain MRI. A standardized neurological examination and questionnaire, neuropsychological examination and brain MRI were performed in 122 patients with DM2 and 56 matched controls. Measures of peripheral neuropathy were vibration threshold, a sensory examination sum score and the Toronto Clinical Neuropathy Scoring System. Neuropsychological test scores were expressed in standardized z-values across five predetermined cognitive domains. White matter lesions and cortical and subcortical atrophy were rated on MRI. Overall 38% of the patients with DM2 and 12% of the controls were classified as having any neuropathy (p<0.001). Patients with DM2 had a lower performance on the neuropsychological tests, more white matter lesions (p<0.01) and more atrophy (p<0.01) than controls. Within the DM2 group none of the measures of peripheral neuropathy was related to MRI abnormalities or cognitive dysfunction (linear regression analyses, adjusted for age, education, sex). We conclude that peripheral neuropathy in patients with DM2 is not related to cognitive dysfunction and brain abnormalities. This indicates that central and peripheral neurological complications of DM2 might have different etiologies. PMID- 17850823 TI - Progressive myopathy with a combined respiratory chain defect including Complex II. AB - Biochemical defects in the respiratory chain are mostly associated with deficiencies in Complexes I, III and IV, caused by nuclear or mitochondrial DNA mutations. Combined defects including Complex II have been reported very rarely and have muscular symptoms as the main manifestation, including muscle weakness, exercise intolerance and myoglobinuria. We report a patient with a fatal progressive myopathy and muscle biopsy showing diffuse reduction in succinate dehydrogenase activity, ragged red fibers and intense lipid accumulation. Cytochrome c oxidase (COX) histochemistry demonstrated 30% of fibers with increased subsarcolemmal staining while 27% were COX negative. Western blotting analysis showed reduction in the expression of the 39 kDa subunit of Complex I, subunit II of Complex IV and the 70 kDa subunit of Complex II. Our findings suggest that the patient had a complex pattern of mitochondrial dysfunction affecting multiple respiratory chain complexes (I, II and IV) and fatty acid metabolism. This report adds a new histological pattern associated to combined deficiencies of respiratory chain with involvement of Complex II and shows that this disease may be fatal with a rapid progression. PMID- 17850824 TI - Analysis of a minimal model for p53 oscillations. AB - Oscillatory behaviours in genetic networks are important examples for studying the principles underlying the dynamics of cellular regulation. Recently the team of Alon has reported a surprisingly rich oscillatory response of the p53 tumor suppressor to irradiation stress et al. [Lahav, G., Rosenfeld, N., Sigal, A., Geva-Zatorsky, N., Levine, A.J., Elowitz, M.B., Alon, U., 2004. Dynamics of the p53-Mdm2 feedback loop in individual cells. Nat. Genet. 36 (2), 147-150; Geva Zatorsky, N., Rosenfeld, N., Itzkovitz, S., Milo, R., Sigal, A., Dekel, E., Yarnitzky, T., Liron, Y., Polak, P., Lahav, G., Alon, U., 2006. Oscillations and variability in the p53 system. Mol. Syst. Biol. 2, 2006.0033]. Several models for this system have been proposed by different groups, based essentially on negative feedback loops. In this paper we investigate in detail oscillations and stability in a deterministic time delayed differential model of the core circuit for p53 expression. This model is representative of a class of modelling approaches of this system, based on a "minimal" set of well-established biomolecular regulations. Depending on the protein degradation rates we show the existence of bifurcations between a stable steady state and oscillations both in presence and absence of stress. PMID- 17850825 TI - Zoledronic acid-induced IPP/ApppI production in vivo. AB - Bisphosphonates are currently the most important class of anti-resorptive drugs used for the treatment of diseases involving excess bone resorption. Recently we discovered a new mechanism of action for bisphosphonates. Previously it has been shown that nitrogen-containing bisphosphonates (N-BPs) are not metabolized. However, our studies revealed that N-BPs induce formation of a novel pro apoptotic ATP analog (ApppI), as a consequence of the inhibition of FPP synthase in the mevalonate pathway, and the subsequent accumulation of isopentenyl pyrophosphate (IPP) in vitro. The primary aim of the current study was to determine whether zoledronic acid (a N-BP) induces IPP/ApppI formation in vivo. Mass spectrometry was used to identify whether in vivo administration of zoledronic acid-induced IPP/ApppI production by mouse peritoneal macrophages or bone marrow cells. IPP/ApppI could be detected in extracts from peritoneal macrophages isolated from zoledronic acid-treated animals. Increasing IPP/ApppI accumulation was determined up to 7 days after drug injection, indicating prolonged FPP synthase inhibition by zoledronic acid. Importantly, this is the first report of in vivo production of ApppI, supporting the biological significance of this molecule. PMID- 17850826 TI - NT-702 (parogrelil hydrochloride, NM-702), a novel and potent phosphodiesterase inhibitor, improves reduced walking distance and lowered hindlimb plantar surface temperature in a rat experimental intermittent claudication model. AB - NT-702 (parogrelil hydrochloride, NM-702), 4-bromo-6-[3-(4-chlorophenyl)propoxy] 5-[(pyridin-3-ylmethyl)amino]pyridazin-3(2H)-one hydrochloride, a novel phosphodiesterase (PDE) inhibitor synthesized as a potent vasodilatory and antiplatelet agent, is being developed for the treatment of intermittent claudication (IC) in patients with peripheral arterial disease. We assessed the efficacy of NT-702 in an experimental IC model as compared with cilostazol and additionally investigated the pharmacological property in vitro and ex vivo. NT 702 selectively inhibited PDE3 (IC(50)=0.179 and 0.260 nM for PDE3A and 3B) more potently than cilostazol (IC(50)=231 and 237 nM for PDE3A and 3B) among recombinant human PDE1 to PDE6. NT-702 inhibited in vitro human platelet aggregation induced by various agonists (IC(50)=11 to 67 nM) and phenylephrine induced rat aortic contraction (IC(50)=24 nM). Corresponding results for cilostazol were 4.1 to 17 microM and 1.0 microM, respectively. NT-702 (3 mg/kg or more) significantly inhibited ex vivo rat platelet aggregation after a single oral dose. For cilostazol, 300 mg/kg was effective. In a rat femoral artery ligation model, NT-702 at 5 and 10 mg/kg repeated oral doses twice a day (BID) for 13 days significantly improved the reduced walking distance while the lowered plantar surface temperature was improved at 2.5 mg/kg and more. Cilostazol also improved the walking distance and surface temperature at 300 mg/kg BID but significant difference was only observed for surface temperature on day 8. These results suggest that NT-702 can be expected to have therapeutic advantage for IC. PMID- 17850827 TI - Plasma lysophosphatidic acid level and serum autotaxin activity are increased in liver injury in rats in relation to its severity. AB - Lysophosphatidic acid (LPA) is a lipid mediator with multiple biological actions. We have reported that LPA stimulates hepatic stellate cell proliferation and inhibits DNA synthesis in hepatocytes, suggesting that LPA might play some role in the liver. We have found that plasma LPA level and serum autotaxin (ATX) activity were increased in patients with chronic hepatitis C. However, the clinical significance of LPA and its synthetic enzyme, autotaxin (ATX), is still unclear. To determine whether the increase of plasma LPA level and serum ATX activity might be found generally in liver injury, we examined the possible modulation of them in the blood in rats with various liver injuries. Plasma LPA level and serum ATX activity were increased in carbon tetrachloride-induced liver fibrosis correlatively with fibrosis grade, in dimethylnitrosamine-induced acute liver injury correlatively with serum alanine aminotransferase level or in 70% hepatectomy as early as 3 h after the operation. Plasma LPA level was correlated with serum ATX activity in rats with chronic and acute liver injury. ATX mRNA in the liver was not altered in carbon tetrachloride-induced liver fibrosis. Plasma LPA level and serum ATX activity are increased in various liver injuries in relation to their severity. Whether increased ATX and LPA in the blood in liver injury is simply a result or also a cause of the injury should be further clarified. PMID- 17850828 TI - Gonadotropin regulation of RIP140 messenger ribonucleic acid expression in the rat ovary. AB - Female mice null for receptor-interacting protein 140 (RIP140) are infertile because of the failure of follicle rupture. The present study examined gonadotropin regulation of RIP140 expression in immature rat ovary. Treatment with PMSG increased ovarian RIP140 mRNA and protein levels. In contrast, hCG treatment rapidly inhibited RIP140 mRNA and protein levels within 1-3 h. RIP140 mRNA was detected in theca cells of growing follicles in untreated ovary and in granulosa cells in PMSG-treated ovary. Interestingly, hCG treatment reduced RIP140 mRNA levels in granulosa cells of preovulatory follicles, but not of growing follicles. Neither treatment of immature rats with diethylstilbestrol in vivo nor of immature granulosa cells with FSH in vitro affected RIP140 mRNA levels. Treatment of immature granulosa cells with 17beta-estradiol in vitro, however, stimulated RIP140 mRNA levels. In cultured preovulatory granulosa cells, RIP140 mRNA levels were stimulated at 1 h and then declined to below control levels by 3 h after LH treatment. Treatment with MDL-12,330A, an inhibitor of adenylate cyclase, or chelerythrine chloride, an inhibitor of protein kinase C (PKC), inhibited LH-stimulated RIP140 gene expression. Furthermore, forskolin or TPA treatment for 1 h mimicked the stimulatory action of LH, indicating the involvement of both adenylate cyclase and PKC pathways. These results demonstrate the stimulation by PMSG and inhibition by hCG of RIP140 expression in granulosa cells of preovulatory follicles in the rat ovary. PMID- 17850829 TI - Role of the Met(287)Thr polymorphism in the AS3MT gene on the metabolic arsenic profile. AB - Chronic exposure to arsenic involves a biotransformation process leading to the excretion of methylated metabolites, such as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), as well as the parental inorganic species (As(III) and As(V)). Inter-individual variations in arsenic biotransformation have been reported and polymorphisms affecting the genes involved in arsenic biotransformation have been considered as one of the plausible explanations for this variation. Coding and flanking regions of the human arsenic methyltransferase (AS3MT) gene have been analysed in 50 Chilean men exposed to arsenic. Nine polymorphisms were found, including one non-synonymous SNP at exon 9 (Met(287)Thr) with an allele frequency of 0.14. Other four changes occurred at potentially regulatory regions: a variable number of tandem repeats (VNTR) at the 5'-untranslated region (UTR5'), a G/C substitution at the promoter region, a GC/AT substitution inside the VNTR, and a G/A substitution at the 3'-untranslated region (UTR3'). The rest of polymorphisms were located in non-coding regions: a T/G substitution in intron 1, a CTC deletion in intron 2 and a TTT and ATT insertions in intron 5. In addition, the individual urinary arsenic profiles were analysed. Our results indicate that genetic polymorphisms in AS3MT contribute to inter-individual variation in arsenic biotransformation and, therefore, may contribute to inter-individual variations in risk of arsenic toxicity and arsenic carcinogenesis. Individuals with the Met(287)Thr polymorphism displayed increased arsenic methylation and might be at increased risk for toxic and genotoxic effects of arsenic exposure if, as the classical arsenic metabolic pathway indicates, methylation enhances toxicity. PMID- 17850830 TI - Histone acetylation and chromatin signature in stem cell identity and cancer. AB - Cancers are traditionally viewed as a primarily genetic disorder, however this view has recently been modified by compelling evidence arguing that epigenetic events play important roles in most human cancers. Deregulation of epigenetic information (encoded in DNA methylation and histone modification patterns) in cells with pluripotent potential may alter defining properties of stem cells, self-renewal and differentiation potential, leading to cancer initiation and progression. The level of compaction of chromatin dictates accessibility to genomic DNA and therefore has a key role in establishing and maintaining distinct gene expression patterns and consequently pluripotent state and differentiation fates of stem cells. Unique properties of stem cells defined as "stemness" may be determined by acetylation and methylation of histones near gene promoters that regulate gene transcription, however these histone modifications elsewhere in the genome may also be important. In this review, we discuss new insights into possible mechanisms by which histone acetyltransferases (HATs) and histone acetylation in concert with other chromatin modifications may regulate pluripotency, and speculate how deregulation of histone marking may lead to tumourigenesis. PMID- 17850831 TI - Reduced implicit and explicit sequence learning in first-episode schizophrenia. AB - A high prevalence of deficits in explicit learning has been reported for schizophrenic patients, but it is less clear whether these patients are impaired in implicit learning. Deficits in implicit learning indicative of a fronto striatal dysfunction have been reported using a serial reaction-time task (SRT), but the impact of typical neuroleptic medication and chronicity remains controversial. The present study compared 37 patients with first-episode schizophrenia treated with atypical neuroleptics and 37 healthy matched control participants on two sequence learning tasks: a modified SRT for implicit sequence learning and a serial generation task (SGT) for explicit sequence learning. The two tasks were designed to be procedurally equivalent, in order to provide better comparability between implicit and explicit performance. Although unaffected in global cognitive functioning, schizophrenic patients were significantly impaired in implicit and explicit sequence learning. Deficient sequence learning in schizophrenic patients was neither related to psychopathology nor to chlorpromazine equivalent daily dosage. As performance was impaired even though patients were exclusively treated with atypical neuroleptics, the present findings concur with converging evidence of a sequence learning deficit inherent in schizophrenia. This deficit would be consistent with a fronto-striatal dysfunction and might constitute a crucial factor for the acquisition of new information. PMID- 17850832 TI - Is the parietal lobe necessary for recollection in humans? AB - An intriguing puzzle in cognitive neuroscience over recent years has been the common observation of parietal lobe activation in functional neuroimaging studies during the performance of human memory tasks. These findings have surprised scientists and clinicians because they challenge decades of established thinking that the parietal lobe does not support memory function. However, direct empirical investigation of whether circumscribed parietal lobe lesions might indeed be associated with human memory impairment has been lacking. Here we confirm using functional magnetic resonance imaging that significant parietal lobe activation is observed in healthy volunteers during a task assessing recollection of the context in which events previously occurred. However, patients with parietal lobe lesions that overlap closely with the regions activated in the healthy volunteers nevertheless exhibit normal performance on the same recollection task. Thus, although the processes subserved by the human parietal lobe appear to be recruited to support memory function, they are not a necessary requirement for accurate remembering to occur. PMID- 17850834 TI - Sesquiterpene lactones as chemotaxonomic markers in genus Anthemis. AB - Sesquiterpene lactones isolated from the genus Anthemis are used as chemotaxonomic markers. The obtained results support with some exceptions the botanical classification in Flora Europaea. Discrepancy between the lactone profile, cluster analysis and classification of A. melampodina, A. macedonica and A. austriaca in the genus Anthemis is discussed. The lactone composition of the undescribed as an European species A. plutonia correlates well with the guaianolide containing group of sect. Hiorthia. PMID- 17850833 TI - Meta-analysis of Go/No-go tasks demonstrating that fMRI activation associated with response inhibition is task-dependent. AB - FMRI studies of response inhibition consistently reveal frontal lobe activation. Localization within the frontal cortex, however, varies across studies and appears dependent on the nature of the task. Activation likelihood estimate (ALE) meta-analysis is a powerful quantitative method of establishing concurrence of activation across functional neuroimaging studies. For this study, ALE was used to investigate concurrent neural correlates of successfully inhibited No-go stimuli across studies of healthy adults performing a Go/No-go task, a paradigm frequently used to measure response inhibition. Due to the potential overlap of neural circuits for response selection and response inhibition, the analysis included only event-related studies contrasting No-go activation with baseline, which allowed for inclusion of all regions that may be critical to visually guided motor response inhibition, including those involved in response selection. These Go/No-go studies were then divided into two groups: "simple" Go/No-go tasks in which the No-go stimulus was always the same, and "complex" Go/No-go tasks, in which the No-go stimulus changed depending on context, requiring frequent updating of stimulus-response associations in working memory. The simple and complex tasks demonstrated distinct patterns of concurrence, with right dorsolateral prefrontal and inferior parietal circuits recruited under conditions of increased working memory demand. Common to both simple and complex Go/No-go tasks was concurrence in the pre-SMA and the left fusiform gyrus. As the pre-SMA has also been shown to be involved in response selection, the results support the notion that the pre-SMA is critical for selection of appropriate behavior, whether selecting to execute an appropriate response or selecting to inhibit an inappropriate response. PMID- 17850835 TI - Polyhydroxyserratane triterpenoids from Diphasiastrum complanatum. AB - Serratane triterpenoids were identified from Diphasiastrum complanatum (L.) Holub, including serratane-3alpha,14alpha,15alpha,20beta,21beta,24,29-heptol (1), 3alpha,20beta,21beta-trihydroxyserrat-14-en-24-oic acid (2), 3beta,20beta,21beta trihydroxyserrat-14-en-24-oic acid (3), 3alpha,20beta,21beta-trihydroxy-16 oxoserrat-14-en-24-oic acid (4), and 16-oxolyclanitin-29-yl E-4'-hydroxyl-3' methoxycinnamate (5) on the basis of their spectroscopic data as well as nine known analogs. PMID- 17850836 TI - Genetic characterization of Indian peste des petits ruminants virus (PPRV) by sequencing and phylogenetic analysis of fusion protein and nucleoprotein gene segments. AB - Peste des petits ruminants (PPR) is an important viral disease of sheep and goats, endemic in India. The study was undertaken to characterize the local PPRV by sequencing fusion (F) protein and nucleoprotein (N) gene segments and phylogenetic analysis, so as to focus on genetic variation in the field viruses. Selected regions of PPRV genome were amplified from clinical samples collected from 32 sheep and goats by RT-PCR and the resulting amplicons were sequenced for phylogenetic analysis. The phylogenetic tree based on the 322bp F gene sequences of PPRV from five different locations clustered them into lineage 4 along with other Asian isolates. While the 425bp N gene sequences revealed a different pattern of branching, yielding three distinct clusters for Nigerian, Turkey and Indian isolates. Thus, classification of PPRV into lineages based on the N gene sequences appeared to yield better picture of molecular epidemiology for PPRV. PMID- 17850837 TI - Synthesis of chalcone derivatives on steroidal framework and their anticancer activities. AB - Chalcone derivatives on estradiol framework have been synthesized. Some of the derivatives showed potent anticancer activity against some human cancer cell lines. Compounds 9 and 19 showed potent activity against MCF-7, a hormone dependent breast cancer cell line. Chalcone 7 was further modified to the corresponding indanone derivative (19) using the Nazarov reaction, which showed better activity than the parent compound against the MCF-7 breast cancer cell line. Active anticancer derivatives were also evaluated for osmotic hemolysis using the erythrocyte as a model system. It was observed that chalcone derivatives showing cytotoxicity against cancer cell lines did not affect the fragility of erythrocytes and hence may be considered as non-toxic to normal cells. PMID- 17850838 TI - Priming dose of phenylhydrazine protects against hemolytic and lethal effects of 2-butoxyethanol. AB - Protection against a high dose of a toxicant by prior exposure to another toxicant is called heteroprotection. Our objective was to establish a heteroprotection model in RBCs. Female Sprague Dawley rats treated with an LD90 dose of 2-butoxyethanol (BE, 1500 mg/kg in water, 5 ml/kg po) 14 days after priming with 0.9% NaCl suffered 90% mortality by 15 days, whereas all rats receiving the LD90 dose of BE 14 days after priming with phenylhydrazine (PHZ, 125 mg/kg in 0.9% NaCl, 3 ml/kg po) survived. Hematocrit decreased from normal 45% to 24% by day 3 after PHZ priming and improved thereafter. Increasing the time interval between the priming and LD90 dose to 21 days abolished the heteroprotection. RBCs obtained on days 7 and 14 after PHZ priming unlike those on day 21 were resilient to the hemotoxic metabolite of BE, butoxyacetic acid (BAA). Unaltered hepatic alcohol and aldehyde dehydrogenase activities upon PHZ priming suggested that bioactivation of BE to BAA was unaffected. Lower renal (6 and 12 h) and hepatic (12 h) BAA levels and 3 fold higher excretion of BAA in PHZ primed rat urine suggested a protective role of toxicokinetics. Higher erythropoietin, reticulocytes, and resiliency of PHZ-primed rat RBCs indicated that newly formed RBCs are resilient to hemolytic BAA. The antioxidant levels in the PHZ-primed rat RBCs did not indicate a protective role in heteroprotection. In conclusion, the resistance of PHZ-primed rats against BE-induced hemotoxicity and lethality is mediated by a combination of altered toxicokinetics, robust erythropoiesis, and resiliency of new RBCs. PMID- 17850839 TI - Intrathecal injection of glutamate receptor antagonists/agonist selectively attenuated rat pain-related behaviors induced by the venom of scorpion Buthus martensi Karsch. AB - The present study investigated the involvement of spinal glutamate receptors in the induction and maintenance of the pain-related behaviors induced by the venom of scorpion Buthus martensi Karsch (BmK). (5R,10S)-(+)-5-methyl-10,11-dihydro-5H dibenzo[a,d]-cyclohepten-5-10-imine hydrogen maleate (MK-801; 40nmol; a non competitive NMDA receptor antagonist), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 40nmol; a non-NMDA receptor antagonist), dl-amino-3-phosphonopropionic acid (dl-AP3; 100nmol; a group I metabotropic glutamate receptor antagonist) and 4-aminopyrrolidine-2,4-dicarboxylate (APDC; 100nmol; a group II metabotropic glutamate receptor agonist) were employed. On intrathecal injection of glutamate receptor antagonists/agonist before BmK venom administration by 10min, BmK venom induced spontaneous nociceptive responses could be suppressed by all tested agents. Primary thermal hyperalgesia could be inhibited by MK-801 and dl-AP3, while bilateral mechanical hyperalgesia could be inhibited by CNQX and dl-AP3 and contralateral mechanical hyperalgesia could be inhibited by APDC. On intrathecal injection of glutamate receptor antagonists/agonist after BmK venom injection by 4.5h, primary thermal hyperalgesia could be partially reversed by all tested agents, while bilateral mechanical hyperalgesia could only be inhibited by APDC. The results suggest that the role of spinal glutamate receptors may be different on the various manifestations of BmK venom-induced pain-related behaviors. PMID- 17850840 TI - An unsupervised learning model of neural plasticity: Orientation selectivity in goggle-reared kittens. AB - The selectivities of neurons in primary visual cortex are often considered to be adapted to the statistics of natural images. Accordingly, simple cell-like tuning emerges when unsupervised learning models that seek sparse representations of input probabilities are trained on natural scenes. However, orientation tuning develops before structured vision starts, rendering these previous results moot as models of activity-dependent development. A more stringent examination of such models comes from experiments demonstrating altered neural response properties in goggle-reared kittens. We show that an unsupervised learning model of cortical responsivity accounts well for the dramatic effects of stimulus driven development during goggle-rearing. PMID- 17850841 TI - Contribution of post-receptoral cells to the a-wave of the human photopic electroretinogram. AB - ERGs were recorded to red flashes (0.01-50 phcdsm(2)) presented against a steady background (2000 sctd) or 0-300 ms after its suppression. The cone a-wave was altered in form and increased in amplitude in the dark. Peak amplitudes were doubled when the dark period was 50-100 ms and also when it was 150-200 ms. Measurement of the a-wave at fixed times showed that amplitude increase occurred at times later than 6-8 ms. The a-wave receives a significant negative-signal contribution from two post-receptoral mechanisms. These are adapted by weak backgrounds and recover their sensitivity extremely rapidly in the dark. The cone photocurrent alone contributes 40-70% of peak amplitude depending on stimulus intensity. PMID- 17850842 TI - Air concentrations of PCDD/Fs, PCBs and PCNs using active and passive air samplers. AB - The concentrations of polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), polychlorinated biphenyls (PCBs) and polychlorinated naphthalenes (PCNs) were determined in air samples collected at four sampling sites located in two zones of Barcelona (Spain): near a municipal solid waste incinerator (MSWI) and a combined cycle power plant (3 sites), and at a background/control site. Samples were collected using high-volume active samplers. Moreover, 4 PUF passive samplers were deployed at the same sampling points during three months. For PCDD/Fs, total WHO-TEQ values were 27.3 and 10.9 fg WHO-TEQm(-3) at the urban/industrial and the background sites, respectively. The sum of 7 PCB congeners and the Sigma PCN levels were also higher at the industrial site than at the background site. In order to compare active and passive sampling, the accumulated amounts of PCDD/Fs, PCBs and PCNs in the four passive air samplers, as well as the total toxic equivalents in each sampling site were also determined. To assess the use of PUF passive samplers as a complementary tool for PCDD/F, PCB and PCN monitoring, sampling rates were calculated in accordance with the theory of passive air samplers. PUF disks allowed establishing differences among zones for the POP levels, showing that they can be a suitable method to determine POP concentrations in air in areas with various potential emission sources. Although both particle and gas phase were sorbed by the PUFs, data of gas phase congeners are more reproducible. PMID- 17850843 TI - Thermal desorption of polychlorobiphenyls from contaminated soils and their hydrodechlorination using Pd- and Rh-supported catalysts. AB - This paper reports about a combined technology for soil remediation from PCBs using the thermal desorption technique coupled with the catalytic hydrogenation of recovered PCBs. The reactor is a bench scale rotating desorption furnace through which nitrogen is flushed and used as carrier gas of desorbed PCBs. The latter are condensed into an hexane or hexane-acetone (1:1 v/v) solution that is then hydrogenated using phosphate-supported Pd or Rh as catalyst. The analysis of the treated soil, under variable operative conditions (temperature and desorption time), shows that the total (99.8%) decontamination from PCBs occurs. The recovery yield of the desorbed PCBs is better than 75% and the subsequent hydrogenation reaches 63% of the collected PCBs in 5h or 100% in 12h. PMID- 17850844 TI - Quantum-chemical descriptors for estimating hemolytic activity of aliphatic and aromatic methacrylates. AB - Methacrylates such as methyl methacrylate (6), triethyleneglycol dimethacrylate (5) and bisphenol A glycidyldimethacrylate, bis-GMA, (8) are widely used as materials in dental resins perturbation of the phosphatidylcholine-cholesterol interaction. Such effects of aromatic methacrylates may be involved in their marked hemolytic action. PMID- 17850845 TI - Sorption of imidazolium-based ionic liquids to aquatic sediments. AB - Ionic liquids (ILs) have received much attention as "green" alternatives to traditional solvents because they do not evaporate, eliminating concerns over fugitive emissions. However, if ionic liquids are used in industrial applications, they may enter aquatic systems via effluent, and their fate and transport may be influenced by sorption to sediments. In this study, we conducted batch mixing experiments with four alkylmethylimidizolium-based ILs and four types of aquatic sediments to asses the capacity for natural aquatic sediments to remove these chemicals from the water column. The concentration isotherms were non linear with point estimates of the distribution coefficient (K(d)) decreasing with increasing concentration. Apparent distribution coefficients ranged from 7.9 to 95.7l kg(-1) at an initial concentration of 0.5mM and were positively related to sediment organic matter (SOM) content. These K(d) values indicate that the ILs did not sorb strongly to the tested sediments. Increased alkyl chain length did not lead to increased sorption suggesting that hydrophobic interactions were not the most important sorption mechanism. We conclude that aquatic sediments have a limited capacity to sorb alkylmethylimidazolium ILs and that the transport of these contaminants in aquatic systems will not be strongly attenuated by sediments. PMID- 17850846 TI - In vitro toxicity assay using human bronchial epithelial cell, Beas-2B, for the screening of toxicological risk of dioxin-like compounds sampled from small sized Korean waste incineration plants. AB - To test the suitability of cell bioassay as a tool for screening the toxicological risk of dioxin-like compounds, an in vitro toxicity assay was performed using samples obtained from small sized Korean waste incineration plants. Stress-related gene expression, cell viability, apoptosis, DNA damage and cell cycles were investigated as toxicological indicators of the polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDDs/DFs) exposed human bronchial epithelial cell, Beas-2B. Of the stress-related genes, the expressions of the aryl hydrocarbon receptor (AhR), cytochrome P450 (CYP) and p53 genes were most significantly induced by exposure to PCDDs/DFs. Exposure of Beas-2B cells to PCDDs/DFs sampled from waste incinerators was sufficient for the expression of noticeable cytotoxic and genotoxic effects. Increased number of cells in the G1 phase in PCDDs/DFs treated samples suggests PCDDs/DFs might lead to alteration in the cell cycle. Statistical tests revealed significant correlations between the PCDDs/DFs concentration and the AhR and CYP gene expression/cell viability/DNA damage. Different from AhR-mediated bioanalytical assay using genetically modified cell line, the present study has been focused on the evaluation of toxicological effects of dioxin-like compounds using normal human cell line. The results of this study have demonstrated that PCDDs/DFs samples from waste incinerators can be applied to cell bioassays for the evaluation of the toxicity of dioxin-like compounds obtained from field samples, and the use of stress related gene expression assay and cytotoxic/genotoxic test systems would appear to be relevant for preliminary screening of the risk associated with dioxin-like chemicals from waste incinerators. PMID- 17850847 TI - Concentrations of polychlorinated biphenyls (PCBs) in water, sediment, and aquatic biota in the Houston Ship Channel, Texas. AB - Polychlorinated biphenyls (PCBs) were quantified in water, sediment, and catfish and crab tissue collected from the Houston Ship Channel (HSC) in Texas. The total concentrations of the 209 PCB congeners ranged from 0.49 to 12.49 ng l(-1), 4.18 to 4601 ng g(-1) dry wt, 4.13 to 1596 ng g(-1) wet wt, and 3.44 to 169 ng g(-1) wet wt, in water, sediment, catfish and crab tissue, respectively. All media showed maximum concentrations greater than studies in other regions with the highest concentrations occurring in the most industrialized segments of the channel. Inter-media correlations suggested that sediment is a source to water. Galveston Bay sediment concentrations compared to a previous study showed a declining trend though the rate of the decline may be slowing. Detailed homolog profiles revealed that the industrialized part of the channel may be receiving PCB-laden sediment from its tributaries. An unusually high fraction of the deca chlorinated congener (PCB-209) was found in all media. Seen in only a few other studies and in previous air concentrations in the channel, this may point to unusual Aroclor mixtures used in the history of the HSC or to contemporary sources from local industry. A comparison of PCB concentrations obtained using Aroclor, representative congener, and all congener methods, indicated that Aroclors are not an appropriate surrogate for total PCBs and that the NOAA NST method is more representative than the NOAA EPA method. PMID- 17850848 TI - Evaluation of the corrosivity of the soil through its chemical composition. AB - The study of the soil as a corrosive environment has become necessary, since material deterioration caused by physico-chemical interactions between the material and the environment has been displayed. In this work, the corrosivity of the soil in the Southeastern region of Brazil has been studied. In this region, 16 samples have been collected at varied points located at the vicinity of a slurry pipeline. For a better understanding of the soil corrosivity, the following analyses were conducted in solutions prepared with the soil samples: chromatographic analyses for ion determination; plasma emission for metal determination and pH measurements. It was concluded that the number of elements present in the soil composition is important for the determination of the corrosivity action of this environment. The assessment of the soil corrosivity is important to select efficient methods to protect buried structures and avoid soil contamination induced by pipeline failures. PMID- 17850849 TI - Mercury transport and bioaccumulation in riverbank communities of the Alvarado Lagoon System, Veracruz State, Mexico. AB - The Alvarado Lagoon System (ALS) is located within the Papaloapan River Basin in southern Veracruz, Mexico. The ALS is a shallow system (2 m) connected to the Gulf of Mexico through a narrow sea channel. There are a large number of riverbank communities within the ALS that are dependent upon its biological productivity for comestible and economic subsistence. The purpose of this project was to determine the levels of mercury in water, sediment, fish, and hair samples from within the Papaloapan River Basin and to characterize the risk of Hg exposure to the individuals that reside in these communities. Water and fish samples were collected during the wet (September 2005) and dry (March 2003 and 2005) seasons. Hair samples, dietary surveys, and sediment samples were obtained during the wet and dry seasons of 2005. Total Hg in the water column ranged from 1.0 to 12.7 ng/L. A strong correlation (R(2)=0.82; p<0.001) between total Hg and total suspended solids in the water column suggests that particulate matter is a transport mechanism for Hg within the lagoon system. Total Hg in the sediments ranged from 27.5 to 90.5 ng Hg/g dry weight with no significant difference between the 2005 wet and dry seasons. There was a mild, but significant, correlation between total Hg and % carbon for the March 2005 sediment samples (R(2)=0.435; p=0.020), suggesting that Hg is associated with organic matter on the solid phase. Concentrations of total Hg in fish and shellfish harvested from the ALS ranged from 0.01 to 0.35 microg Hg/g wet. The levels of total Hg in hair ranged from 0.10 to 3.36 microg Hg/g (n=47) and 58% of the samples were above 1.00 microg Hg/g. The findings from this study suggest that individuals who frequently consume fish and shell fish containing low levels of Hg (<0.3 microg/g) can accumulate low to moderate body burdens of Hg, as indicated by hair Hg concentrations>1.0 microg/g, and may be at risk for experiencing low dose mercury toxicity. PMID- 17850850 TI - Retrievable vena cava filters: key considerations. AB - Retrievable filters are a new generation of inferior vena cava (IVC) filters and represent an attractive option because they may be either left in place permanently or safely retrieved after a quite long period when they become unnecessary. In this review the currently available literature regarding retrievable IVC filters is summarized and their efficacy and safety is discussed. Moreover, the appropriate indications for their use are reviewed. Retrievable filters are becoming safer and easier to use; in fact the bioengineering research has optimized the technical characteristics of these devices, in order to reduce the incidence of possible complications. However, there are important unresolved issues, including the appropriate maximum implantation time, the possibility to safely and efficaciously remove the filters without being compromised by entrapped clots, and the use of anticoagulation during the implantation and periremoval periods. Large prospective cohort studies or randomized trials are strongly warranted to definitely clarify the beneficial role of these devices. PMID- 17850851 TI - Inherited platelet function disorders versus other inherited bleeding disorders: an Indian overview. AB - Inherited deficiencies of plasma proteins involved in blood coagulation generally lead to lifelong bleeding disorders, whose severity is directly proportional to the degree of factor deficiency. Platelet and other coagulation factors play an important role in the haemostasis mechanism. We attempted to study the prevalence of inherited platelet function disorders (PFDs) and correlate with other coagulation factor disorders in the Indian population. Patients with PFDs and other coagulation factor disorders who presented at our hospital during the 5 year period (from January, 2001 to December, 2005) were the subjects of the study. A total of 1576 patients were diagnosed to have congenital bleeding disorders including PFDs, von Willebrand disease, haemophilia A and B and rare coagulation disorder cases. Haemophilia A (HA) was the most common and was seen in 52.31% of the patients followed by total PFDs seen in 27.77% of the patients. Based on severity of the disease, the results of PFDs were highly significant when compared to haemophilia and von Willebrand disease (VWD) (p=0.000). Severity was found higher in HA (77.8%) followed by HB (69.6%) and was found lower for PF3 availability defect (9.0%). It has been concluded that the prevalence of PFDs is relatively low as compared to coagulation factors related disorder and also it has been established that type-1 VWD is relatively less frequent in India as compared to the West. PMID- 17850852 TI - Characterization of the effects of ryanodine, TTX, E-4031 and 4-AP on the sinoatrial and atrioventricular nodes. AB - AIMS: To characterize the effects of inhibition of Ryanodine receptor (RyR), TTX sensitive neuronal Na+ current (iNa), "rapidly activating" delayed rectifier K+ current (iKr) and ultrarapid delayed rectifier potassium current (IKur) on the pacemaker activity of the sinoatrial node (SAN) and the atrioventricular node (AVN) in the mouse. METHODS: The structure of mouse AVN was studied by histology and immunolabelling of Cx43 and hyperpolarization-activated, cyclic nucleotide binding channels (HCN). The effects of Ryanodine, TTX, E-4031 and 4-AP on pacemaker activities recorded from mouse intact SAN and AVN preparations have been investigated. RESULTS: Immuno-histological characterization delineated the structure of the AVN showing the similar molecular phenotype of the SAN. The effects of these inhibitors on the cycle length (CL) of the spontaneous pacemaker activity of the SAN and the AVN were characterized. Inhibition of RyR by 0.2 and 2 microM Ryanodine prolonged CL by 42+/-12.3% and 64+/-18.1% in SAN preparations by 163+/-72.3% and 241+/-91.2% in AVN preparations. Inhibition of TTX-sensitive iNa by 100 nM TTX prolonged CL by 22+/-6.0% in SAN preparations and 53+/-13.6% in the AVN preparations. Block of iKr by E-4031 prolonged CL by 68+/-12.5% in SAN preparations and 28+/-3.4% in AVN preparations. Inhibition of iKur by 50 microM 4 AP prolonged CL by 20+/-3.4% in SAN preparations and 18+/-3.0% in AVN preparations. CONCLUSION: Mouse SAN and AVN showed distinct different response to the inhibition of RyR, TTX-sensitive INa, IKr and iKur, which reflects the variation in contribution of these currents to the pacemaker function of the cardiac nodes in the mouse. Our data provide valuable information for developing virtual tissue models of mouse SAN and AVN. PMID- 17850853 TI - Percent surface area involvement is a predictor of lymph node metastasis in endometrial cancer. AB - OBJECTIVE: To determine if percent surface area involvement (SAI) of tumor in endometrial cancer is predictive of lymph node metastasis. METHODS: A retrospective study was performed of all patients diagnosed with endometrial cancer at Magee Women's Hospital between January 1990 and December of 1995. Papillary serous and clear cell histologic subtypes were excluded. Pathology reports were reviewed for percent SAI, myometrial invasion, grade, histologic subtype, lymphovascular space invasion, and lymph node metastasis. Percent SAI was categorized into three groups: <35%, 35-80%, and >80%. The primary outcome variables were pelvic or periaortic lymph node metastasis. Univariate and multivariate analysis logistic regression models were used to determine predictors of nodal metastasis. RESULTS: Of 558 patient records reviewed, 319 had lymph node dissections performed and 42 (13%) of those patients had positive lymph nodes. Two of 79 (3%) patients with <35% SAI had lymph node metastasis, 17 of 165 (10%) patients with 35-80% SAI had lymph node metastasis, and 23 of 75 (31%) patients with >80% SAI had lymph node metastasis. The percent SAI was significantly associated with lymph node metastasis (p<0.001). Multivariate logistic regression indicated that for patients with >80% SAI, the odds of having lymph node metastasis were 10.8 times (CI 1.3-90.4) that for patients with similar tumor histology, grade, and invasion, but <35% SAI (p=0.03). A subset analysis of patients with superficial myometrial invasion was performed and 16% of patients with <50% myometrial invasion and >80% SAI had positive lymph nodes, while only 1.4% of patients with <50% myometrial invasion and <35% SAI had positive lymph nodes (p=0.02). CONCLUSION: Our analysis indicates that percent SAI is an independent risk factor for lymph node metastasis. Furthermore, assessing SAI with myometrial invasion gives a more accurate prediction of lymph node metastasis than myometrial invasion alone. This becomes clinically relevant when assessing risk factors for lymph node metastasis intraoperatively. PMID- 17850855 TI - Inverse decision theory with applications to screening and diagnosis of cervical intraepithelial neoplasia. AB - OBJECTIVE: Medical decision makers would like to use decision theory to determine optimal treatment strategies for patients, but this requires priors, likelihoods, and losses. It can be very difficult to specify a loss or utility function in a medical setting, especially when considering both patient health outcomes and economic costs. These issues led to the development of Inverse Decision Theory (IDT), which involves determining the set of losses under which a given decision rule is optimal. METHODS: We apply IDT to the current standard of care for the diagnosis and treatment of precancerous lesions to the cervix, using a Bayesian approach to estimate the probabilities associated with diagnostic tests and make inferences about the region of optimality. There are two ways in which Inverse Decision Theory can be useful: (i) if the decision rule of interest is optimal, then we obtain information about the losses for the optimal treatment strategy, and (ii) if the decision rule of interest is not optimal, then we characterize the losses under which it would be optimal, and assess whether or not it contains reasonable values of the losses. RESULTS: This paper introduces important clinical results: in particular, we find that the current standard of care for cervical precancer is probably not optimal, and a new decision rule which requires a confirmatory biopsy for all patients with a positive Pap smear test result is better. CONCLUSION: We have developed a very general and flexible approach for evaluating treatment strategies that could prove useful in a variety of medical applications. PMID- 17850856 TI - Diets enriched in unsaturated fatty acids enhance early embryonic development in lactating Holstein cows. AB - We hypothesized that a diet enriched in alpha-linolenic acid would enhance embryonic development relative to diets enriched in linoleic or saturated fatty acids. Twenty-four lactating Holstein cows (86+/-22 d postpartum) were assigned to one of three diets containing saturated fatty acids (SAT; high in palmitic and stearic acids), whole flaxseed (FLX; high in alpha-linolenic acid) or sunflower seed (SUN; high in linoleic acid). Rations were formulated to provide 750 g supplemental fat/cow/d in all dietary groups. Ovulation (Day 0) was synchronized approximately 20 d after diets began. Ultrasound-guided follicular ablation of all follicles >8 mm was performed 5 d after ovulation; super stimulatory treatments began 2 d after follicular ablation, and embryos were collected non surgically 7 d after AI. Fertilization rate, numbers of follicles and ovulations, and total and transferable embryos did not differ (P>0.05) among dietary groups. Sixty-one transferable embryos were stained and total blastomere number determined. Blastomere number was affected by diet (P<0.01); without regard to stage of development, embryos collected from cows fed SAT had lower (P<0.01) blastomere numbers (mean+/-S.E.M.; 77.1+/-3.9) than those from cows fed FLX (93.4+/-3.3) or SUN (97.2+/-3.5). Differences were most evident in the expanded blastocyst stage; at this stage, embryos of cows fed FLX and SUN diets had more blastomeres (P<0.02) than those of cows fed SAT (115.4+/-6.3, 132.3+/-8.3, and 89.3+/-9.6 cells, respectively). Although our hypothesis was only partially supported, embryonic development was enhanced in Holstein cows fed unsaturated fatty acids compared to those fed saturated fatty acids. PMID- 17850857 TI - Estimation of the potential fertility based upon non-return rates of bulls: using polyacrylamide gel instead of cervical mucus in the sperm penetration test. AB - In the present study, we aimed to develop a polyacrylamide gel that could be used instead of bovine cervical mucus in the cervical mucus penetration test (CMPT) to obtain coherent and replicable results in bulls. The frozen semen samples of six Holstein bulls, which were divided into two fertility groups as low and high according to their non-return rate (NRR), were used. In this study, the modified CMPT (mCMPT) was carried out within 0.25 mL transparent plastic straws with an inner diameter 1.7 mm. The penetration ability of spermatozoa to bovine cervical mucus and to polyacrylamide gels swollen with two different solutions [NaCl (G1) and PBS (G2)] was compared. For the penetration test, the straws filled with cervical mucus and both gels were dipped into thawed semen samples and incubated at 37 degrees C for 15 min. After the incubation, straws were frozen in liquid nitrogen vapour and stored at -20 degrees C. On the evaluation day, the frozen straws were cut at 1.5-1.75 cm (penetration distance range=PDR1), 3.25-3.5 cm (PDR2) and 5.0-5.25 cm (PDR3), beginning from open-end of the straws. The separated frozen parts were then immediately transferred onto special counting slides by pushing with a mandrel and left to thaw. Thawed samples were covered with cover glass and penetrated spermatozoa in these parts were counted. The relation between the results and fertility of bulls was determined. In the tests performed using mucus, the number of spermatozoa determined in the high fertility group was found to be higher at PDR3 (p<0.0001) compared to the low fertility group, while in G1 spermatozoa number was significantly higher at PDR1 and PDR3 (p<0.0001). However, in G2 medium, no significant difference was observed between either of the fertility groups with respect to spermatozoa number determined at all distance ranges. In the study, we have determined that the gel swollen with NaCl produces better results and this gel can be used instead of bovine cervical mucus for the CMPT. Therefore, we have concluded that the penetration test performed by polyacrylamide gel swollen with NaCl can be a suitable technique for estimation of the potential fertility of bull spermatozoa. PMID- 17850858 TI - Western analyses of pregnancy-associated glycoprotein family (PAG) in placental extracts of various mammals. AB - The present study was conducted in order to analyze the immunoreactivity of placental extracts of several animal species and humans against the following three groups of PAG antisera: anti-boPAG-I (R#497), -boPAG-II (R#435), and -caPAG (R#706). Placental proteins were obtained after extraction at neutral pH, followed by ammonium sulfate (A.S.) precipitation, dialysis, and lyophilization. The immunoreactivity of different placental extracts was revealed by the use of monodimensional SDS-PAGE, followed by blotting on nitrocellulose membrane and the identification of immunoreactive proteins after incubation with PAG antisera (Western blot technique). A strong immunoreactivity of proteins from synepitheliochorial placenta (cattle, sheep, goat, bison, buffalo, and deer) was demonstrated in both 20-50% and 50-80% A.S. fractions using the three antisera. Proteins from species with epitheliochorial placenta presented variable profiles of detected PAG-like proteins: in the sow, many immunoreactive forms were revealed by antisera boPAG-I and boPAG-II, whereas in the dromedary, only two forms were revealed by anti-boPAG-II. Concerning other species, our protocols showed for the first time a cross-reaction between PAG antisera with proteins extracted from dog, alpaca, dromedary, sea lion, and human placenta. PMID- 17850859 TI - Predicting interacting and interfacial residues using continuous sequence segments. AB - Development of sequence-based methods for predicting putative interfacial residues is an extremely important task in modeling 3D structures of protein protein complexes. In the present paper we used non-gapped sequence segments to predict both interacting and interfacial residues. We demonstrated that continuous sequence segments do occur at the protein-protein interfaces and showed that continuous interacting interfacial segments (CIIS) of length nine are presented on average, in approximately 37% of the complexes in our dataset. Our results indicate that CIIS consist mostly of interacting strands and/or loops, while the CIIS involving the helixes are scarce. We performed scoring of CIIS using four different scoring mechanisms and found that scores of CIIS differ significantly from the scores calculated for random stretches of residues. We argue that such statistical difference inferred thought the corresponding Z scores could be used for detecting putative interfacial residue segments without using any structural information. This hypothesis was tested on our dataset and benchmarking resulted to 10-60% prediction accuracy depending on type of benchmarking and scoring scheme used in calculations. Such predictions that do not depend on the availability of the 3D structures of monomers can be quite valuable in modeling 3D structures of obligatory complexes, for which structures of separated monomers do not exist. PMID- 17850860 TI - Effect of polyamines on the structure, thermal stability and 2,2,2 trifluoroethanol-induced aggregation of alpha-chymotrypsin. AB - Naturally occurring polyamines are known to interact with a variety of biomolecules and critically involve in some important physiological processes. They have also been shown to influence protein aggregation in vitro in some cases. The aim of the present study was to investigate how polyamines may influence the structure and thermal stability of alpha-chymotrypsin and modulate alcohol-induced aggregation of this protein. Various techniques, including turbidity measurements, tensiometry, DSC, intrinsic fluorescence and far- and near-UV circular dichroism spectroscopy were used to examine the effect of putrescine and spermidine on alpha-chymotrypsin. While slight changes in the secondary and tertiary structure of the protein was observed, a clear stabilizing effect against its thermal unfolding was achieved. Moreover, the polyamines were found to inhibit TFE-induced aggregation at 32% TFE and promote formation of non native alpha-helices in the protein structure. Based on the observed increase in surface tension induced by polyamines, it is suggested that their effects on enhancing thermal stability and alcohol-induced alpha-helices formation may be due to their kosmotropic properties. PMID- 17850861 TI - In vitro three-stage continuous fermentation of wheat arabinoxylan fractions and induction of hydrolase activity by the gut microflora. AB - In vitro fermentations were carried out by using a model of the human colon to stimulate microbial activities of gut bacteria. The model consisted of a three stage culture system. Bacterial populations were evaluated under the effect of three types of arabinoxylan, a nonstarch polysaccharide derived from wheat, the water-unextractable arabinoxylan fraction (WU-AX), WU-AX pretreated with exogenous xylanase and the soluble water-extractable arabinoxylan fraction (WE AX). The xylanase pretreated (WU-AX) had a stimulatory effect upon colonic bifidobacteria throughout all three vessels. Counts of Bacteroides spp. and Clostridium spp. were also both significantly reduced. Addition of the WU-AX substrates to the first vessel resulted in induction of bacterial synthesis of extracellular hydrolytic enzymes xylanase and ferulic acid esterase which are both required for bacterial metabolism of WU-AX; this induction was significantly greater with the xylanase treated WU-AX. PMID- 17850862 TI - Porcine small intestinal submucosa sheets as a scaffold for human bone marrow stem cells. AB - Native small intestinal submucosa (SIS) sheet was prepared by removal of inside and outside layer of porcine jejunum. The acid treated SIS sheet was also prepared by dipping of native SIS sheet in acetic acid solution. The native or acid treated SIS sheets exhibited elastic and soft property on touch. The surface of native SIS sheet appears to be covered with thin and long collagen fibers entangled into networks. The fibers and fibrils at acid treated SIS sheet disappeared due to the acidic erosion of collagen fiber. The water uptake of acid treated SIS sheet (1300%) was higher than that of the native SIS sheet (500%). The cell morphology and proliferation of human bone marrow stem cells (hBMSCs) on SIS sheet was examined. The hBMSCs on the SIS sheet showed a flattened morphology, while cells in the polyglycolic acid (PGA) mesh showed rounded cell morphology. The cell viability on native or acid treated SIS sheet was higher than that of PGA mesh. The hBMSCs in both native and acid treated SIS sheet were grown at a similar rate. The number of adhering hBMSCs increased with incubation time. Thus, we could confirm that native or acid treated SIS sheet could act as a potential scaffold to enhance the hBMSCs proliferation by providing probably natural environments. PMID- 17850863 TI - The role of endothelial cell attachment to elastic fibre molecules in the enhancement of monolayer formation and retention, and the inhibition of smooth muscle cell recruitment. AB - The endothelium is an essential modulator of vascular tone and thrombogenicity and a critical barrier between the vessel wall and blood components. In tissue engineered small-diameter vascular constructs, endothelial cell detachment in flow can lead to thrombosis and graft failure. The subendothelial extracellular matrix provides stable endothelial cell anchorage through interactions with cell surface receptors, and influences the proliferation, migration, and survival of both endothelial cells and smooth muscle cells. We have tested the hypothesis that these desired physiological characteristics can be conferred by surface coatings of natural vascular matrix components, focusing on the elastic fiber molecules, fibrillin-1, fibulin-5 and tropoelastin. On fibrillin-1 or fibulin-5 coated surfaces, endothelial cells exhibited strong integrin-mediated attachment in static conditions (82% and 76% attachment, respectively) and flow conditions (67% and 78% cell retention on fibrillin-1 or fibulin-5, respectively, at 25 dynes/cm2), confluent monolayer formation, and stable functional characteristics. Adhesion to these two molecules also strongly inhibited smooth muscle cell migration to the endothelial monolayer. In contrast, on elastin, endothelial cells attached poorly, did not spread, and had markedly impaired functional properties. Thus, fibrillin-1 and fibulin-5, but not elastin, can be exploited to enhance endothelial stability, and to inhibit SMC migration within vascular graft scaffolds. These findings have important implications for the design of vascular graft scaffolds, the clinical performance of which may be enhanced by exploiting natural cell-matrix biology to regulate cell attachment and function. PMID- 17850864 TI - Bovine caruncular epithelial cell line (BCEC-1) isolated from the placenta forms a functional epithelial barrier in a polarised cell culture model. AB - In the bovine synepitheliochorial placenta key sites of fetal-maternal interaction are placentomes consisting of maternal caruncles interdigitating with fetal cotyledons. The aim of this study was to establish an epithelial cell line from caruncles of pregnant cows and to develop a model to study restricted trophoblast invasion, pathogenesis of pregnancy associated diseases and pathways of infection and transport. Primary epithelial cells were isolated, successfully subcultured for 32 passages and cryopreserved at various stages. The cultures were termed bovine caruncular epithelial cell line-1 (BCEC-1). Cytokeratin, zonula occludens-1 protein and vimentin but neither alpha-smooth muscle actin nor desmin were detected by immunofluorescence performed every 5 (+/-1) passages. These results were confirmed by Western blotting. BCEC-1 were then cultured either without matrix or on fibronectin or collagen coated Transwell polyester membrane inserts, respectively, enabling separate access to the basal or apical epithelial compartments. Transmission and scanning electron microscopy of BCEC-1 revealed ultrastructural features also observed in vivo, such as apical microvilli and junctional complexes. Transepithelial electrical resistance (TEER) was measured regularly and revealed an increase with advancing confluence in all cultures. Cultures on coated inserts reached confluence and corresponding TEER levels at an earlier stage. In addition, the cells were tested negative for bovine virus diarrhoea (BVD) virus, but were permissive for the virus. In conclusion, the BCEC-1 cell line retained characteristics of maternal caruncular epithelial cells as observed in vivo and in primary cell cultures and thus will be a highly useful tool for future studies of pathways of invasion, fetal maternal communication, transport and infection. PMID- 17850865 TI - RNF24, a new TRPC interacting protein, causes the intracellular retention of TRPC. AB - TRPCs function as cation channels in non-excitable cells. The N-terminal tails of all TRPCs contain an ankyrin-like repeat domain, one of the most common protein protein interaction motifs. Using a yeast two-hybrid screening approach, we found that RNF24, a new membrane RING-H2 protein, interacted with the ankyrin-like repeat domain of TRPC6. GST pull-down and co-immunoprecipitation assays showed that RNF24 interacted with all TRPCs. Cell surface-labelling assays showed that the expression of TRPC6 at the surface of HEK 293T cells was greatly reduced when it was transiently co-transfected with RNF24. Confocal microscopy showed that TRPC3 and TRPC6 co-localized with RNF24 in a perinuclear compartment and that RNF24 co-localized with mannosidase II, a marker of the Golgi cisternae. Using a pulse-chase approach, we showed that RNF24 did not alter the maturation process of TRPC6. Moreover, in HEK 293T cells, RNF24 did not alter carbachol-induced Ca(2+) entry via endogenous channels or TRPC6. These results indicate that RNF24 interacts with TRPCs in the Golgi apparatus and affects TRPC intracellular trafficking without affecting their activity. PMID- 17850866 TI - Regulation of the cellular localization and function of human transient receptor potential channel 1 by other members of the TRPC family. AB - Members of the Canonical Transient Receptor Potential (TRPC) family of ionic channels are able to form homo- and heterotetrameric channels. Depending on the study, TRPC1 has been detected on both the surface and inside the cell, probably in the endoplasmic reticulum (ER). Likewise, TRPC1 has been described both as a store-operated channel and as one unable to function when forming a homotetramer. It is possible that the apparent differences in the expression and function of TRPC1 are due to its association with other proteins, possibly from the same TRPC family. In the present study we used confocal microscopy and a fluorescently tagged TRPC1 to examine the localization of this protein when co-expressed with other members of the TRPC family. Whole-cell and single channel electrophysiological recordings were conducted to study the function of TRPC1 expressed alone or co-expressed with other members of the TRPC family. A FRET based calcium sensor fused to TRPC1 was used to assess the functionality of the intracellular TRPC1. Our results showed that TRPC4 and TRPC5 were able to increase the amount of membrane-expressed TRPC1 as evaluated by confocal microscopy and patch clamp recordings. The FRET-based calcium sensor fused to TRPC1 strongly suggests that this protein forms ER-expressed functional homotetrameric channels activated by agonists coupled to the IP(3) cascade. These results indicate that TRPC1 is a multifunctional protein able to form intracellular calcium release channels when expressed alone, and plasma membrane channels when co-expressed with TRPC4 or TRPC5, but not TRPC3 or TRPC6. Both (ER and plasma membrane) forms of the channel are activated upon addition of agonists coupled to the IP(3) cascade. PMID- 17850867 TI - Lower leukocytes at initial diagnosis may predict poor outcome of very late relapse of acute lymphoblastic leukemia. AB - We have reported a rare case of acute lymphoblastic leukemia (ALL) recurring 19 years after the first presentation. Since 1984, 36 relapse cases 10 years or more after the first diagnosis have been reported. All cases were childhood ALL with a low to standard risk. Twenty-six attained CR2, and 18 of them remained in sustained CR2. The sustained CR2 ratio was 80% without transplantation. Sustained CR2 ratio was significantly lower in patients with lower leukocytes (<10 x 10(9)l(-1)) at initial presentation. A very late relapse of ALL remains chemosensitive, and its prognosis is not unfavorable. PMID- 17850868 TI - Molecular cloning and expression analysis of the ASC gene from mandarin fish and its regulation of NF-kappaB activation. AB - Apoptosis-associated speck-like protein containing a CARD (ASC) is an adaptor protein that has a bipartite domain structure, an N-terminal PYRIN domain and a C terminal caspase-recruitment domain (CARD). In this study, we cloned the mandarin fish ASC cDNA (mfASC), which consisted of 899bp with a 115bp 5'-UTR and a 181bp 3'-UTR. The open reading frame encoded 201 amino acids. The mfASC shows 37% identity to an ASC orthologue from zebrafish. The mfASC has two protein-protein interaction domains, an N-terminal PYRIN domain and a C-terminal CARD domain. The mfASC gene structure was determined and had a length of 3954bp with four exons separated by three introns. Northern blot analysis showed that mfASC mRNA is constitutively expressed in the head kidney, gill, hind kidney, spleen and intestine. In vitro studies, mfASC fused with green fluorescent protein appeared as a speck in the transfected 293T cells. When transiently overexpressed in 293T cells, mfASC inhibited NF-kappaB activity with or without tumor necrosis factor (TNFalpha) or lipopolysacharide (LPS) stimulation. PMID- 17850869 TI - Identification of a lepidopteran matrix metalloproteinase with dual roles in metamorphosis and innate immunity. AB - Matrix metalloproteinases (MMPs) are key enzymes in mammalian tissue remodeling and inflammation. Recently, we postulated that an endogenous MMP expressed in the lepidopteran model Galleria mellonella during metamorphosis causes degradation of collagen-IV, which in turn results in activation of innate immunity. Here, we report that degradation of collagen-IV by hemocytes is enhanced upon injection of bacterial lipopolysaccharide (LPS), and that this activity is sensitive to the MMP-inhibitor GM6001. Therefore, we screened for enzymes behind this activity and identified the first MMP from Lepidoptera (Gm1-MMP), and the third from insects. Gm1-MMP shares homology with the first MMP from Drosophila (Dm1-MMP) known to be essential for tissue remodeling during metamorphosis. Using quantitative real time reverse transcriptase polymerase chain reaction (RT-PCR) analysis, we confirmed up-regulation of Gm1-MMP expression after pupation, when extracellular matrix breakdown of larval tissues occurs. In addition, we determined that LPS challenge induces Gm1-MMP expression in hemocytes, implicating its participation in collagen-IV degradation upon septic injury. These results suggest dual roles of Gm1-MMP in innate immunity and metamorphosis. Interestingly, our phylogenetic analysis elucidates that Gm1-MMP share highest similarity with human MMP-19 and MMP-28, whose functions in mammalian wounding and inflammatory response have recently been demonstrated; hence, the present findings may provide insights into the evolutionarily conserved features of MMPs. PMID- 17850870 TI - National monitoring of PCDD/DFs in environmental media around incinerators in Korea. AB - To examine the levels of PCDD/DFs pollution in environmental samples in the vicinity of various incinerators, the levels of PCDD/DFs in air and soil samples collected near 17 incinerators and stack emission gases were investigated between 2003 and 2006. A total of 434 soil, 28 stack emission gas, and 38 air samples were analyzed for their PCDD/DFs concentrations. The PCDD/DFs concentrations in the flue gas samples ranged from 0.02 to 16.41 ng I-TEQ/Sm(3), with an arithmetical mean value of 3.13 ng I-TEQ/Sm(3). The PCDD/DFs concentrations in the air samples ranged from 0.032 to 0.965 pg I-TEQ/Sm(3). The soil samples contained between N.D. and 153.23 pg I-TEQ/g-dry, with an average of 7.36 pg I TEQ/g-dry. These levels were generally consistent with or lower than many previous studies. The average PCDD/DFs levels in the soil samples decrease with increasing distance from the incinerator. From the PCDD/DFs level gradient from each plant, a distance of 500 m is suggested as being under the influence of an incinerator. PMID- 17850871 TI - Immunogenicity and therapeutic efficacy of phage-displayed beta-amyloid epitopes. AB - In vitro and in vivo studies indicate that Alzheimer's Disease (AD) could be prevented or treated by active immunization against self-peptide beta-amyloid. In this study, we compared the immunogenicity of different regions of beta-amyloid, displayed on filamentous phages. We established that a filamentous phage displaying epitope 2-6 (AEFRH) of beta-amyloid at the N-terminus of Major Capside Protein (phage fdAD(2-6)) is more immunogenic than a phage displaying epitope 1-7 (DAEFRHD) that differs only in flanking residues. Monthly injections of fdAD(2-6) trigger a robust anti-beta-amyloid antibody response, and afford a significant reduction of plaque pathology in a mouse model of AD, whereas the same treatment, performed with phage fdAD(1-7), induces a lower anti-beta-amyloid titer and does not protect from amyloid deposition. "Memory" anti-amyloid antibodies induced by a single prime-boost cycle with vaccine fdAD(2-6), that have a lower titer compared to antibodies induced by monthly restimulations, do not prevent plaque pathology. Our data show that optimization of epitope display is essential in vaccine design, and suggest that the titer of the anti-amyloid response is the crucial parameter to obtain therapeutic efficacy in vivo. PMID- 17850872 TI - Spatial distribution of histone methylation during MHC class II expression. AB - We have previously reported that Major Histocompatibility Complex (MHC) class II can be induced by histone deacetylase inhibitors (HDACi) in the absence of class II transactivator (CIITA). Here we characterized the histone modifications associated with the CIITA-dependent (IFN-gamma induced) and -independent (HDACi induced) MHC class II expression. We demonstrate that both IFN-gamma and HDACi induced MHC class II expression exhibited enhanced histone H3, H4 acetylation and H3K4me3 at the MHC class II promoter while H3K9me3 was decreased. In contrast, high levels of H3K36me3 were detected at exons 3 and 5 but not at the promoter or the locus control region (LCR). Interestingly, high levels of H3K79me2 were only detected at the promoter and exon 3 of the B cell lines while the level remained low and unchanged despite active MHC class II expression induced by either IFN gamma or HDACi treatment. Constitutive expression of the CIITA protein by stable transfection of a CIITA deficient B cell line restored the H3K79me2 to a level comparable to its cell of origin. This data demonstrates that, although regulated by different pathways, both IFN-gamma and HDACi treatments resulted in similar patterns of histone modifications and that HDACi induce both histone methylation and acetylation. In addition, the different spatial distribution of the lysine methylation markers along the gene suggests that these modifications play a distinctive role during different phases of the transcription process. PMID- 17850873 TI - Molecular cloning, genomic organization and recombinant expression of a crustin like antimicrobial peptide from black tiger shrimp Penaeus monodon. AB - A novel crustin-like antimicrobial peptide (Crus-likePm) was identified from haemocytes of Penaeus monodon. The deduced amino acid sequence of a Crus-likePm consists of 124 amino acid residues of the mature peptide and a signal peptide of 17 amino acid residues. The mature peptide contains a glycine-rich domain at the N-terminus and 12 conserved cysteine residues containing a single WAP domain at the C-terminus. Phylogenetic tree and sequence comparison clearly confirmed a distinct between a Crus-likePm and other shrimp crustins. Genomic organization and upstream region of a Crus-likePm gene was investigated. The gene consisted of two exons and one intron. The 5'-flanking regions of a Crus-likePm gene contain multiple putative transcription factor binding sites. mRNA transcript of a Crus likePm was found to be abundantly expressed in haemocyte and highly up-regulated after Vibrio harveyi injection. The mature Crus-likePm was cloned into the pET28b with an N-terminal hexa-histidine tag fused in-frame, and expressed in E. coli. The purified recombinant Crus-likePm showed strong antimicrobial activity against both Gram-positive and Gram-negative bacteria including V. harveyi, a major pathogenic bacteria in shrimp aquaculture. PMID- 17850874 TI - Time-related changes in constitutive and inducible nitric oxide synthases in the rat striatum in a model of Huntington's disease. AB - Excitotoxicity and oxidative stress are mechanisms involved in the neuronal cell death induced by the intrastriatal injection of quinolinic acid (QUIN) as a model of Huntington's disease. Production of nitric oxide by nitric oxide synthase (NOS) has been proposed to participate in QUIN-induced neurotoxicity; however, the precise role of NOS in QUIN-induced toxicity still remains controversial. In order to provide further information on the role of NOS isoforms in QUIN toxicity, we performed real time RT-PCR and immunohistochemistry of inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (nNOS) and determined Ca(2+) dependent and Ca(2+)-independent NOS activity in a temporal course (3-48h), after an intrastriatal injection of QUIN to rats. NOS isoforms exhibited a transitory expression of mRNA and protein after QUIN infusion: eNOS increased between 3 and 24h, iNOS between 12 and 24h, while nNOS at 35 and 48h. Ca(2+)-independent activity (iNOS) did not show any change, while Ca(2+)-dependent activity (constitutive NOS: eNOS/nNOS) exhibited increased levels at 3h. Our results support the participation of Ca(2+)-dependent NOS isoforms during the toxic events produced at early times after QUIN injection. PMID- 17850875 TI - Impaired mitochondrial energy metabolism and neuronal apoptotic cell death after chronic dichlorvos (OP) exposure in rat brain. AB - The present study elucidates a possible mechanism by which chronic organophosphate exposure (dichlorvos 6 mg/kg bw, s.c. for 12 weeks) causes neuronal degeneration. Mitochondria, as a primary site of cellular energy generation and oxygen consumption represent itself a likely target for organophosphate poisoning. Therefore, the objective of the current study was planned with an aim to investigate the effect of chronic dichlorvos exposure on mitochondrial calcium uptake, oxidative stress generation and its implication in the induction of neuronal apoptosis in rodent model. Mitochondrial preparation from dichlorvos (DDVP) treated rat brain demonstrated significant increase in mitochondrial Ca(2+) uptake (644.2 nmol/mg protein). Our results indicated decreased mitochondrial electron transfer activities of cytochrome oxidase (complex IV) along with altered mitochondrial complex I, and complex II activity, which might have resulted from elevated mitochondrial calcium uptake. The alterations in the mitochondrial calcium uptake and mitochondrial electron transfer enzyme activities in turn might have caused an increase in malondialdehyde, protein carbonyl and 8-hydroxydeoxyguanosine formation as a result of enhanced lipid peroxidation, and as well as protein and mtDNA oxidation. All this could have been because of enhanced oxidative stress, decreased GSH levels and also decreased Mn-SOD activity in the mitochondria isolated from dichlorvos treated rat brain. Thus, chronic organophosphate exposure has the potential to disrupt cellular antioxidant defense system which in turn triggers the release of cytochrome c from mitochondria to cytosol as well as caspase-3 activation in dichlorvos treated rat brain as revealed by immunoblotting experiments. Low-level long-term organophosphate exposure finally resulted in oligonucleosomal DNA fragmentation, a hallmark of apoptosis. These studies provide an evidence of impaired mitochondrial bioenergetics and apoptotic neuronal degeneration after chronic low-level exposure to dichlorvos. PMID- 17850876 TI - Effect of hydrazine deproteination on bone mineral phase: a critical view. AB - Over the last 30 years several techniques have been developed to separate bone matrix and bone mineral, in order to allow for a study of each component independently of the other. Preservation of original characteristics of the phase studied after isolation has always been a great challenge for all such techniques. The hydrazine deproteination procedure, first proposed by Termine, has been one of the processes most widely used for studying bone mineral. It is found to be one of the most effective, notwithstanding controversy over its efficiency in bone deproteination and criticism regarding possible changes it could make to the characteristics of bone mineral. In this work, we have studied the possible chemical and physical alterations caused by the hydrazine deproteination process to bone mineral from rats and to other materials of biological interest. Materials were characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), X-ray diffractometry (XRD), inductive coupled plasma-optical emission spectroscopy (ICP-OES), C-H-N analysis and infrared spectroscopy (FTIR), before and after hydrazine deproteination. Finally, here we present a comprehensive discussion on the criticism of hydrazine deproteination. The experimental results obtained in this work, even when compared to the results in the literature, show that most widespread criticism to the hydrazine deproteination process is not completely justified. PMID- 17850877 TI - Use of different thresholds of prior antimicrobial use in defining exposure: impact on the association between antimicrobial use and antimicrobial resistance. AB - OBJECTIVES: Although many studies have explored the association between antimicrobial use and antimicrobial resistance, definitions of "exposure" (i.e., prior antimicrobial use) differ across such studies. Specifically, it has been noted that some studies define "exposure" as any antimicrobial use, while others require the administration of at least 24 or 48 h of an antimicrobial to constitute "exposure." The impact of different definitions of exposure on final study results is unknown. We conducted the current study to determine the impact of varying the minimum threshold of prior antimicrobial use to define exposure status in studies of antimicrobial resistance. METHODS: We used a dataset from a prior study of risk factors for fluoroquinolone (FQ) resistant Pseudomonas aeruginosa (FQRPA) to address the study aim. Four separate multivariable models of risk factors for FQRPA were built. Each model defined a different threshold for the duration of antimicrobial administration to determine "exposure" to that antimicrobial: (1) no threshold (i.e., a subject is considered exposed if any use of the antimicrobial was documented); (2) >24 h of use of the antimicrobial is necessary to be considered exposed; (3) >48 h of use is required; and (4) >72 h of use is required. Except for these definitions, the four multivariable models were built in exactly the same way, each using prior FQ use as the primary risk factor of interest. RESULTS: Among 872 P. aeruginosa isolates included in the original dataset, 332 (38.2%) were FQ-resistant. Each of the four multivariable models identified prior FQ use as an independent risk factor for FQRPA. However, as increasingly strict thresholds were used, the association between FQ use and FQRPA increased. Furthermore, prior use of an agent with activity against anaerobic bacteria was associated with FQRPA in models 2, 3 and 4, but not in model 1. CONCLUSIONS: The use of different thresholds to define prior "exposure" to antimicrobials altered the associations between antimicrobial use and resistance. Stricter thresholds resulted in a higher estimate of the association between antimicrobial use and resistance. Furthermore, different risk factors may be identified depending on how exposure is defined. Greater attention to this issue is necessary to optimize identification of modifiable risk factors for resistance as well as accurately compare results across studies. PMID- 17850879 TI - Antidepressant monotherapy in pre-bipolar depression; predictive value and inherent risk. AB - OBJECTIVE: To identify specific treatment-emergent symptoms in response to antidepressant therapy in depression preceding bipolar disorder. METHODS: Retrospective chart review of response to antidepressants in "pre-bipolar" depression, compared to a matched unipolar sample. RESULTS: Family history of completed suicide (p=0.0003) and bipolar disorder (p=0.004) were more common in the pre-bipolar subgroup. Earlier age of onset of diagnosed depression (p=0.005) as well as even earlier episodes of untreated retrospectively diagnosed major depression (p<0.0001) were associated with a future bipolar course. The pre bipolar group was less likely to respond to antidepressant treatment (p=0.009). Treatment-emergent "mixed" symptoms (two or more symptoms of DSM IV mania, mood lability, irritability/rage with co-existing depression) and in particular, "serious symptoms" (treatment emergent or increased agitation, rage or suicidality) occurred more commonly in the bipolar group. The two variables that best accounted for the between-group differences in logistic regression, were early age at first symptoms of depression and treatment-emergent agitation. CONCLUSIONS: Family history of completed suicide and/or bipolar disorder, early onset of depressive symptoms as well as treatment-emergent "mixed" symptoms are common in depression preceding the diagnosis of bipolar disorder. PMID- 17850878 TI - Neuroprogesterone: key to estrogen positive feedback? AB - In the cycling female rat, estradiol and progesterone induce reproductive behavior and the surge of luteinizing hormone (LH) needed for ovulation. Circulating estradiol of ovarian origin induces progesterone receptors in the preoptic area and hypothalamus. Sequential activation of estrogen receptors (ER) and progesterone receptors coordinates reproductive physiology and behavior. In ovariectomized and adrenalectomized (ovx/adx) rats, administration of estradiol alone is sufficient to initiate an LH surge, and central infusion of aminoglutethimide (AGT), a blocker of the P450 side chain cleavage enzyme, disrupted the estrous cycle of intact rats without affecting peripheral estradiol levels, suggesting that an endogenous source of progesterone remains in these animals. In ovx/adx rats, progesterone levels in the hypothalamus increase prior to the LH surge, and inhibition of progesterone synthesis prevents the LH surge, suggesting that hypothalamic neuroprogesterone is necessary for estrogen positive feedback. In support of the idea that estradiol induces neuroprogesterone, estradiol increased expression of the progesterone-synthesizing enzyme 3beta hydroxysteroid dehydrogenase (3beta-HSD) in the hypothalamus before the LH surge. Further, in vitro experiments demonstrate that estradiol stimulates progesterone synthesis in astrocytes, considered to be the most active steroidogenic cells in the CNS. To stimulate neurosteroidogenesis, estradiol acts through membrane ER and type 1a metabotropic glutamate receptors (mGluR1a) to increase free cytoplasmic calcium ([Ca(2+)](i)) via activation of the PLC-IP(3) pathway. Estradiol-induced progesterone synthesis is mimicked by thapsigargin-induced release of IP(3) receptor-sensitive Ca(2+) stores in astrocyte cultures. Thus, estradiol-induced progesterone synthesis is dependent on membrane ERs that act through mGluR1a to activate the PLC-IP(3) pathway. This neuroprogesterone also facilitated proceptive behavior. Blocking either progesterone synthesis or progesterone receptor in estrogen-primed ovx/adx prevented proceptive but not receptive behaviors. PMID- 17850880 TI - Interleukin-18 and interleukin-12 in maternal serum and spontaneous preterm delivery. AB - INTRODUCTION: Mice disrupted for the interleukin (IL)-18 gene appear more disposed to preterm delivery (PTD) induced by inflammation. A synergy between IL 18 and IL-12 has been suggested. The objective of this study was to investigate a possible relation between human maternal serum levels of IL-18, IL-12 and spontaneous PTD. MATERIALS AND METHODS: A cohort of 93 consecutive women with symptoms of threatening PTD on admission was enrolled at the delivery ward, Aarhus University Hospital, Denmark. MEASURES: Serum IL-18 and IL-12 measured using Luminex xMAP technology. Endpoint: PTD before 34 weeks gestation. RESULTS: Pregnant women admitted with symptoms of threatening PTD and delivering before 34 weeks of gestation had significantly lower levels of IL-18 compared to women delivering at or after 34 weeks of gestation (medians: 14.5 versus 26.6 pg/ml; p=0.035). IL-12 levels were not different in women delivering before or after 34 weeks of gestation. Patients having low IL-18 (below the 25-percentile) and high IL-12 (above the 75-percentile) had a twofold increase in risk of delivering before 34 weeks of gestation (RR 2.1 [1.7-2.6]). CONCLUSION: Results from this study indicate, that low serum IL-18 level could be associated with PTD in women with symptoms of PTD. A possible interaction between IL-18 and IL-12 was found, as the risk of delivering before 34 weeks is increased with the combination of low IL-18 and high IL-12, but further studies are warranted to investigate these interleukins and their possible role in PTD. PMID- 17850881 TI - Catechol-O-methyltransferase gene and obsessive-compulsive symptoms in patients with recent-onset schizophrenia: preliminary results. AB - The catechol-O-methyltransferase (COMT) gene is a candidate gene for schizophrenia because of its role in the breakdown of dopamine in the prefrontal cortex. The COMT gene contains a functional polymorphism changing enzyme activity that has been associated with some neuropsychiatric (endo)phenotypes, e.g. cognitive performance and anxiety. In this study we investigated the association between the COMT Val(158)Met polymorphism and obsessive-compulsive symptoms in patients with schizophrenia. Severity of obsessive-compulsive symptoms in 77 male patients with recent-onset schizophrenia was assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and the COMT Val(158)Met polymorphism was genotyped for these patients. We found a significant effect of the COMT genotype on Y-BOCS scores: the Val/Val genotype was associated with the highest Y-BOCS scores, whereas patients with the Met/Met genotype had the lowest Y-BOCS scores. Our data suggest that the COMT high-activity Val allele is associated with more obsessive-compulsive symptoms in young patients with schizophrenia. These results support the hypothesis that the COMT Val(158)Met polymorphism may be a modifier gene for the symptomatology of schizophrenia. PMID- 17850882 TI - Characterization of mast cell numbers and subtypes in biopsies from the gastrointestinal tract of dogs with lymphocytic-plasmacytic or eosinophilic gastroenterocolitis. AB - It has been suggested but not proven that hypersensitivity type I reactions are involved in the pathogenesis of canine inflammatory bowel disease (IBD). The main effector cells in type I hypersensitivity reactions are mast cells (MCs). Canine MCs, as human MCs, can be subdivided into three subtypes according to their content of mast cell-specific proteases: tryptase (MCT), chymase (MCC), or tryptase and chymase bearing MCs (MCTC). In this study, numbers and subsets of mast cells were investigated in biopsies from the gastrointestinal tract of dogs with histopathologically confirmed lymphocytic-plasmacytic enteritis (LPE) (n=4), lymphocytic-plasmacytic colitis (LPC) (n=1) and eosinophilic gastroenterocolitis (EGE) (n=11). Paraffin sections of formalin-fixed samples from the stomach, small intestine (duodenum, jejunum, ileum) and colon were stained by using a metachromatic staining method (kresylecht-violet; KEV) and a combined enzyme histochemical and immunohistochemical technique for chymase and tryptase. Additionally, immunohistochemistry with antibodies against T cells (CD3), macrophages (myeloid/histiocyte antigen) and IgA, IgG and IgM bearing cells was conducted. Quantitative evaluation of mast cells and semiquantitative scoring of immunohistochemically stained cells were performed. Between the two histopathologically defined groups clear differences concerning mast cell numbers were detected. In most affected intestinal tissue locations of dogs with LPE/LPC a decrease in metachromatically (kresylecht-violet) stained granule-containing MCs and immunohistochemically stained MCT,C,TC was found. This reduction could be due to mast cell degranulation, a T helper cell 1 dominated reaction pattern or a "thinning out" due to increasing T cells, IgA and IgG bearing cells. Dogs with EGE displayed higher variability in mast cell numbers but most of the affected large and small intestinal locations had increased numbers of MCs. In these cases, T cells, IgA bearing cells and macrophages also increased. Increased numbers of MCs and eosinophils seen in the intestinal mucosa of dogs with EGE could indicate the presence of a type I hypersensitivity reaction (T helper cell 2 pattern) in response to dietary antigens. Changes in cell numbers occurred also in unaffected locations of dogs with LPE/LPC and EGE which showed reduced MCT,C,TC, increased KEV positive cells and partially increased leucocytes and macrophages. PMID- 17850883 TI - Molecular characterization of goose-type lysozyme homologue of large yellow croaker and its involvement in immune response induced by trivalent bacterial vaccine as an acute-phase protein. AB - Lysozyme acts as an innate immunity molecule against the invasion of bacterial pathogens. Here, the cDNA of a goose-type lysozyme (g-lysozyme) was cloned from large yellow croaker (Pseudosciana crocea) by expressed sequence tags (EST) and RACE-PCR techniques. The full-length cDNA of large yellow croaker g-lysozyme (LycGL) is 716 nucleotides (nt) encoding a protein of 193 amino acids (aa), with a theoretical molecular weight of 21.3kDa. The deduced LycGL possessed the typical structural features of g-lysozyme, including three catalytic residues (E71, D84, D101) and four substrate binding sites (L97, L121, L128, G152). Genomic analysis revealed that the LycGL gene consisting of 2383nt, contained five exons interrupted by four introns and exhibited a similar exon-intron organization to its homologues in Japanese flounder and Chinese perch, except for having a much longer intron 1 in the LycGL gene. Recombinant LycGL produced in Pichia pastoris exhibited obvious lytic activity against Micrococcus lysodeikticus and several fish pathogenic bacteria such as Aeromonas sobria, Vibrio alginolyticus, Vibrio parahaemolyticus and Vibrio vulnficus. Tissue expression profile analysis showed that LycGL mRNA was constitutively expressed in all tissues examined, such as spleen, head kidney, intestine, liver, gills and heart, although at a different level. Upon stimulation with trivalent bacterial vaccine, LycGL mRNA levels in intestine, spleen and head kidney were quickly up regulated and had 10.32-, 10.2- and 8.26-fold increases, respectively, and LycGL transcripts in intestine and head kidney reached their peak levels at 24h post induction and then decreased gradually while LycGL mRNA in spleen increased to its highest level at 48h. These results suggest that LycGL may be involved in antibacterial immune response activated by bacterial vaccine as an acute-phase molecule. PMID- 17850884 TI - The role of Blimp-1 in the GC reaction: differential expression of Blimp-1 upon immunization with TD and TI antigens. AB - Humoral responses against thymus-dependent (TD) antigens are characterized by Ig class switch, somatic hypermutations (SHM) and generation of memory. These processes are thought to occur in the specialized environment of the germinal center (GC). Some thymus-independent (TI) antigens, such as native dextran B512 (Dx) can also induce formation of GCs, but the responses do not undergo substantial affinity maturation or induction of memory. Immunization with TI Dx affects later TD responses against the same epitope, reducing Dx specific IgG1. We have studied if the different outcome of the TI- and TD-induced GC reaction is due to differences in plasma cell differentiation. The transcriptional repressor B lymphocyte-induced maturation protein, Blimp-1, was used as a marker for differentiation of plasma cells. We show that TI GCs contain Blimp-1 in early and mature GCs, in contrast to TD-induced GCs which strongly express Blimp-1 only in established GCs. Furthermore, the intensity of the Blimp-1 staining is stronger in TI GCs. In addition, we demonstrate that in TD responses after TI priming the pattern of Blimp-1 expression is a mixture of both TI and TD responses. This is novel evidence since these TD humoral responses against Dx display a TI isotype pattern. PMID- 17850885 TI - The effect of recurrent tonsillitis and adenotonsillectomy on growth in childhood. AB - OBJECTIVE: Tonsil and adenoid hypertrophy may cause recurrent tonsillitis and upper airway obstruction in children. A reduced dietary intake and failure to gain weight is frequently reported by parents of children with a history of recurrent acute tonsillitis and adenotonsiller hypertrophy. The purpose of this prospective study was to evaluate whether surgical treatment of adenotonsillar hypertrophy affects the circulating concentrations of insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) along with IGF-1 SDS and IGFBP-3 SDS's adjusted to age which are more important in evaluating growth in childhood. METHODS: Thirty-eight prepubertal children 24 boys and 14 girls participated in this study. The mean age at surgery was 6.66+/-1.84 years (range 4-10 years). Weight, height, IGF-1 and IGFBP-3 levels and standard deviation scores were evaluated before and 12-18 months after adenotonsillectomy (T&A). RESULTS: The number of infections in a year reduced from 8.6+/-4.4 to 0.37+/-0.68 after operation. The mean weight standard deviation score (SDS) increased significantly after T&A (p<0.01). The mean IGFBP-3 level increased from 1912+/-511.5 to 2989+/ 1125ng/ml (p<0.001) and IGFBP-3 SDS increased from -3.0+/-0.58 SDS to -1.96+/ 1.27 SDS (p: 0.001). However, the mean serum IGF-1 level increased from 80.3+/ 48.5 to 116.8+/-105.9ng/ml (p: 0.135), and IGF-1 SDS increased from -1.36+/-0.51 SDS to -1.31+/-1.14 SDS (p: 0.701), which were both not statistically significant. CONCLUSIONS: We have demonstrated postoperative weight gain and significant increase in IGFBP-3 concentrations and IGFBP-3 SDS, accompanying significant decrease in the number of tonsillitis episodes after adenotonsillectomy. PMID- 17850886 TI - Parental understanding and attitudes of pediatric obstructive sleep apnea and adenotonsillectomy. AB - OBJECTIVE: To explore parental perceptions and knowledge of pediatric obstructive sleep apnea (OSA) and adenotonsillectomy. DESIGN: Cross-sectional study. SETTING: National polling organization. PARTICIPANTS: Population-based sample of 584 parents. INTERVENTION: Online surveys. MAIN OUTCOME MEASURES: Responses to questions regarding knowledge of pediatric OSA and treatment with adenotonsillectomy. RESULTS: Ninety-five percent of parents acknowledged that pediatric OSA is a "serious condition". Fifteen percent considered themselves to be "knowledgeable" about it. One fifth understood that untreated OSA could lead to cardiopulmonary disease, failure to thrive, or behavioral problems, such as attention deficit hyperactivity disorder. Less than 20% knew that pediatric OSA could be treated with adenotonsillectomy. Thirty-seven percent believed adenotonsillectomy to be an "outdated" procedure. Upon learning that adenotonsillectomy can treat OSA, 82% reported they would be eager to have a child with OSA undergo adenotonsillectomy. CONCLUSIONS: The majority of parents do not understand symptoms, consequences and treatment of pediatric OSA secondary to adenotonsillar hypertrophy. Otolaryngologists should be diligent in communicating issues of this disorder with parents and pediatricians. PMID- 17850887 TI - Chemotherapy-induced oral complications in leukemic patients. AB - The adverse effects of chemotherapy frequently involve the oral cavity, but the severity of oral complications caused by different chemotherapy protocols is unknown. OBJECTIVE: To compare the frequency of oral complications in patients with acute lymphoblastic leukemia treated with the GBTLI-93 and BFM protocols. PATIENTS AND METHODS: Twenty patients ranging in age from 2 to 13 years were submitted to visual and tactile examination of the teeth, periodontium and soft tissues on the day of admission and over the 3 weeks following the first phase of chemotherapy. RESULTS: No significant difference in the proportion of patients with complications was observed between the two protocols over the 3 weeks. Complications were more frequent immediately after administration of the chemotherapeutic agents, with a gradual decline over the following 3 weeks. CONCLUSIONS: Oral complications occur in patients with acute lymphoblastic leukemia irrespective of the chemotherapy protocol used for treatment, with a higher frequency being observed in the first week after the beginning of antineoplastic therapy. PMID- 17850888 TI - Safe reliable atraumatic replacement of misplaced paediatric tracheostomy tubes. AB - OBJECTIVE: Displacement of tracheostomy tubes, especially soon after insertion has a high morbidity and mortality rate. We present a safe atraumatic reliable method of tracheostomy tube replacement. SETTING: Tertiary paediatric centre. MATERIALS AND METHODS: The method involves using a suction catheter placed in the trachea. Its position can be confirmed by suctioning tracheal secretions. The catheter can be used to employ the Seldinger technique for replacement of the tracheostomy tube and can be used to jet ventilate the patient if there is failure to site a tube. This buys time while a surgical airway is placed. We also outline the minimum contents of the emergency box, which should be carried at all times by the carers of a child with a tracheostomy. CONCLUSIONS: Use of a suction catheter is a safe reliable atraumatic way of replacing a tracheostomy tube. PMID- 17850890 TI - Failed extubation in the neonatal intensive care unit. AB - OBJECTIVE: To determine the causes of failed extubation in the Neonatal Intensive Care Unit (NICU) and the need for airway intervention. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care children's hospital. PATIENTS: We identified all premature infants (gestational age <37 weeks) admitted to the NICU of a tertiary care children's hospital from January 1998 until December 2006 who underwent direct laryngoscopy and bronchoscopy (DLB) in the operating room (OR) for failed extubation. Data was collected on weight, gestational age, co morbid conditions, number of failed extubations, findings at DLB and whether or not a tracheostomy was performed. RESULTS: DLBs were performed on 63 patients to evaluate the cause of failed extubation. Group A comprised of 50 patients who underwent tracheostomy. They had an average gestational age of 30.0 weeks, birth weight of 1457g and number of failed extubations 2.68. Group B consisted of 13 patients who did not undergo tracheostomy. They had an average gestational age of 34.5 weeks, birth weight of 2309g and number of failed extubations 1.33. 56.0% of the tracheostomy group and 38.5% of the non-tracheostomy group had chronic lung disease (CLD). At endoscopy, 44% of Group A and 23.1% of Group B had some degree of subglottic stenosis. CONCLUSION: Abnormal laryngotracheal findings are common in neonates who fail extubation. When compared to their counterparts with similar co-morbidities, neonates with CLD, gestational age of 30 weeks or below and low birth weight are twice as likely to have subglottic edema and fail extubation. They are also likely to be candidates for a tracheostomy. PMID- 17850891 TI - Inactivation of orthopoxvirus for diagnostic PCR analysis. AB - Diagnoses of ongoing viral infections commonly rely on PCR methodology. Sample material that may contain hazardous virus should be efficiently inactivated in biological containment or bed-side before diagnostic PCR analysis. Surprisingly little documentation is available for inactivation of human viral pathogens by inactivation reagents that allow for subsequent PCR diagnostics. It is now shown that pathogenic DNA viruses (orthopoxvirus) are completely inactivated by a commercially available Roche MagNA Pure lysis/binding buffer as evaluated by subsequent cell culture. However, inactivation reagents are typically toxic and therefore problematic in cell culture. Using the relatively large orthopoxvirus, a method was developed in which virus is precipitated by high-speed centrifugation after inactivation but prior to application onto the target cells, thereby eliminating the cytotoxic effect of the lysis buffer. The results from quantitative PCR analysis indicate that the viral DNA from the completely inactivated virus particles, remain associated to macromolecules and aggregates. The use of inactivation buffers for bed-side inactivation of special patient samples taken for PCR diagnostics should be considered in cases where high containment would otherwise be required. PMID- 17850892 TI - Specific identification of feline panleukopenia virus and its rapid differentiation from canine parvoviruses using minor groove binder probes. AB - Taking into account reports of the isolation of canine parvoviruses (CPVs) from faecal samples of cats, we developed a real-time PCR assay, based on minor groove binder (MGB) probe technology, for rapid discrimination between true feline panleukopenia viruses (FPLVs) from CPVs. The assay takes advantage of a single nucleotide polymorphism at position 3753 of the viral genome (corresponding to residue 323 of the capsid VP2 protein) and of the ability of MGB probes to bind specifically only to perfectly complementary sequences. The FPV/CPV assay was proven to be highly specific, sensitive and reproducible and correlated well with a TaqMan assay able to recognise canine as well as feline parvoviruses. Using this assay for extensive molecular surveys will provide precise information on the real circulation of the CPV antigenic variants, including the new variant 2c, in cat population worldwide. PMID- 17850893 TI - A quantitative assay for measuring clearance of adenovirus vectors by Kupffer cells. AB - Kupffer cells are a major barrier to systemic adenovirus (Ad) gene therapy because they rapidly and efficiently clear virions from the circulation. The lack of a straightforward quantitative technique for selectively measuring uptake of Ad by Kupffer cells has made it difficult to study the mechanisms by which they recognize Ad. A new method was developed that relies on immunofluorescent detection of Ad within Kupffer cells in mouse liver sections, followed by confocal microscopy and computerized image analysis. The method is sensitive, quantitative and reproducible, with a linear range spanning two orders of magnitude. As an example of the utility of this method, it was found that pre injecting mice with polyinosinic acid reduces accumulation of Ad in Kupffer cells by approximately 90%. PMID- 17850894 TI - Porcine plasma ficolin binds and reduces infectivity of porcine reproductive and respiratory syndrome virus (PRRSV) in vitro. AB - Ficolins are collagenous lectins that bind N-acetylated glycans and participate in innate immune responses, including phagocytosis and complement activation. Related collagenous lectins such as mannan binding lectin (MBL) and surfactant proteins A and D possess antiviral activity, but this activity has not been demonstrated for ficolins. In these studies, we used purified porcine plasma ficolin alpha and recombinant ficolin alpha to assess their ability to bind and neutralize porcine reproductive and respiratory virus (PRRSV) in various assays. Recombinant ficolin alpha was designed with a C-terminal 6-histidine tag using a pcDNA3.1 expression vector system in CHO K1 cells. Plasma-purified and recombinant ficolin alpha reduced cytopathic effect of PRRSV-infected Marc-145 cells in neutralization assays and inhibited replication of infectious viral particles in a GlcNAc-dependent manner. In vitro replication determined by plaque assay was inhibited in the presence of plasma-purified ficolin alpha and recombinant ficolin. Immunoreactive plasma ficolin alpha and recombinant ficolin alpha also bound PRRSV-coated wells in a GlcNAc-dependent manner. These studies indicate that porcine ficolin can bind and neutralize a common arterivirus that is a major pathogen of swine. PMID- 17850895 TI - Transplantation of rat neural stem cells reduces stereotypic behaviors in rats after intrastriatal microinfusion of Tourette syndrome sera. AB - Tourette syndrome (TS) is a heterogenous neuropsychiatric disorder. In most cases, tics are self-limited or can be treated by behavioral or pharmacological therapy. However, for some individuals, tics can cause lifelong impairment and life-threatening symptoms, which are intractable to traditional treatment. Neural stem cell (NSC) is a potential tool to treat certain neurological diseases. In this study, we proposed to use neural stem cell transplantation as a novel therapy to treat TS and discussed its efficacy. Wistar rats were microinfused with TS sera into the striatum followed by the transplantation of NSCs or vehicle at the infusion site. The sera of the TS patients were identified to have enriched antineural antibodies. Prior to grafting, rat embryonic NSCs were co cultured with 5-bromodeoxyuridine (Brdu) for 24 h. Stereotypic behaviors were counted at 1, 7, 14 and 21 days after transplantation of NSCs. Morphological analyses revealed that NSCs survived and differentiated into neurons and astrocytes in the striatum 3 weeks after grafting. To sum it up, rat embryonic neural stem cell grafts survived and differentiated in the striatum of TS rat may help relieve stereotypic behaviors of the host. Our results suggest that transplantation of NSCs intrastriatum may have therapeutic potential for TS. PMID- 17850896 TI - Naphthalene disrupts pheromone induced mate search in the amphipod Corophium volutator (Pallas). AB - Many crustaceans communicate with pheromones during mating. In the infaunal amphipod Corophium volutator (Pallas), females release gender-specific waterborne pheromones that guide males in their search for receptive burrowed females. Pollutants that affect the pheromone release or impair the ability of males to detect and respond to chemosensory cues, could profoundly affect mating. C. volutator is commonly found on shallow soft sediments in estuaries and coastal waters, and their reproductive season coincides with intense traffic of leisure boats, which discharge high concentrations of fuel into the water and sediment of these areas. This study shows that sublethal exposure to naphthalene, a polycyclic aromatic hydrocarbon abundant in motor fuel, disturbs chemical communication in C. volutator. This was demonstrated in Y-maze bioassays, where males were allowed to follow female pheromones after separately exposing the males or females to naphthalene spiked sediments (0, 0.5, 5 or 50 microg g(-1) dw, nominal concentrations) for 3 days. The results show that exposure to naphthalene at the two lower concentrations significantly affects the males' response to female pheromones (p<0.05 and p<0.01, respectively). Male search activity was reduced by 27-45% and males could no longer find females by the use of the olfactory sense. Analysed sediment samples, however, indicate that the naphthalene concentrations causing this effect were 2-20 times lower than nominal concentrations. At the highest naphthalene treatment, no significant difference from the controls was found, probably explained by a different exposure regime for these amphipods since they seemingly avoided burrowing in sediments. Female C. volutator produce and release pheromones, despite naphthalene exposure. Disrupted chemical communication in C. volutator may affect the reproductive fitness of males and females with possible consequences for populations in contaminated areas. PMID- 17850897 TI - Limited genetic diversity of the Plasmodium falciparum aquaglyceroporin gene. AB - In Plasmodium falciparum small solutes like water, ammonium, glycerol and others are transported by a parasite-encoded channel into the parasite. The gene encoding this channel is termed P. falciparum aquaglyceroporin (PfAQP) and is a single-copy gene and highly homologous to other aquaporins from other protozoa. Aquaporins are considered to be attractive targets for drug treatment and more so since the human and parasite aquaporins show considerable sequence differences. To investigate whether PfAQP may be suitable as a conserved target for potential aquaporin blocking agents we determined the DNA sequences of PfAQP from 65 parasite strains, either from in vitro cultured laboratory strains or from parasites obtained in an malaria-endemic region of Gabon. Only two non-synonymous mutations were found and functionally tested by a methylamine efflux assay. The efflux activity of all variants tested was similar. The lack of functionally variability suggests an invariable protein core, which may restrict parasite populations from evading therapeutic pressure if PfAQP inhibitors will be found. PMID- 17850898 TI - Cloning, site-directed mutagenesis and expression of cathepsin L-like cysteine protease from Uronema marinum (Ciliophora: Scuticociliatida). AB - A cysteine protease gene (ScCtL) homologous to the cathepsin L genes was isolated from a cDNA library of the scuticociliate parasite (Uronema marinum). To express the ScCtL recombinant protein in heterologous system, 17 codons were redesigned to conform to the standard eukaryotic genetic code using PCR-based site-directed mutagenesis. The synthetic U. marinum procathepsin L (proScCtL) was expressed at high levels in E. coli BL21 (DE3) with pGEX-4T-1 vector, and successfully refolded and purified into a functional and enzymatically active form. The optimal pH for protease activity was found to be 4.5. Like any typical cysteine protease, the enzyme was inhibited by E-64 and leupeptin. A dot-blot immunoassay was conducted in an attempt to determine the reaction abilities and sensitivity of the anti-proScCtL polyclonal antibody to the cytosol and to the membrane fraction from the scuticociliate. Our results suggest that the biochemical characteristics of the recombinant ciliate proScCtL protein are similar to that of the cathepsin L-like cysteine protease, and that the PCR-based site-direct mutated ciliate gene was successfully expressed in a biochemically active form. PMID- 17850899 TI - Detection, purification and characterisation of a secretory alkaline phosphatase from Onchocerca species. AB - An Onchocerca secretory alkaline phosphatase (E.C. 3.1.3.1) of molecular weight 90 kDa when in crude extract, but which dimerises to about 180 kDa upon purification, was detected, purified and characterised. The enzyme was found to be secreted by both O. ochengi and O. volvulus worms. It was shown to be of Onchocerca origin by Western blotting with bovine onchocerciasis sera and by its time-dependent release in cultures. The O. ochengi enzyme was purified to near homogeneity by a combination of polyethylene glycol precipitation, DEAE-cellulose chromatography and preparative electrophoresis. About 0.96 mg of the active enzyme was purified from 48.4 mg of the crude parasite-released products, giving a purification fold of 71.45 and a yield of 8.7%. The purified enzyme exhibited a typical Michaelis-Menten kinetics with optimum activity on p-nitrophenylphosphate (p-NPP) at pH 10.2. Its apparent K(m) for p-NPP was 0.56+/-0.03 mM and it required Mg(2+) and dithiothreitol (DTT) for stability throughout its purification. Sodium dodecyl sulphate at 2% (w/v) did not inhibit the enzyme activity, but apparently stabilised it during freezing. Inorganic phosphate inhibited the enzyme competitively with an apparent inhibition constant (K(i)) of 3.33+/-0.04 mM, whereas l-phenylalanine inhibited it in a mixed way with a K(i) of 3.18+/-0.03 mM. While contributing to the understanding of metabolism in Onchocerca, the present apparently unique enzyme which is likely to serve in the nutrition of the parasite could be further characterised as a macrofilaricide target or diagnostic marker in onchocerciasis. PMID- 17850900 TI - Characterization of beta-tubulin genes in hookworms and investigation of resistance-associated mutations using real-time PCR. AB - Human hookworms (Ancylostoma duodenale, Necator americanus) are a major cause of malnutrition and anemia, particularly in children, and high worm burdens can lead to stunted growth and mental retardation. Mass drug administration (MDA) with benzimidazole (BZ) anthelmintics has the potential to greatly reduce morbidity and infection prevalence. However, such treatment strategies may apply significant selection pressure on resistance alleles. In several Strongylid parasites of livestock, resistance to BZ drugs is associated with single nucleotide polymorphisms (SNPs) in the beta-tubulin isotype-1 gene at codons 167 and 200. As an initial investigation into the possible development of BZ resistance in hookworms, we have cloned and sequenced the beta-tubulin isotype-1 genes of the canine hookworm Ancylostoma caninum and the two human hookworm species A. duodenale and N. americanus. The genomic sequences are highly conserved as evidenced by a similar structure of exons and introns; the 10 exons are of the same length in all three species and code for the same amino acids. The genomic sequences were then used to develop a real-time PCR assay for detecting polymorphisms in codons 167 and 200 in all three species. Hookworm specimens previously obtained from Pemba Island school children who had demonstrated a reduced response to treatment with mebendazole were then examined using the real-time PCR assay. None of the samples revealed significant levels of polymorphisms at these loci. If BZ resistance is present in the hookworm populations examined, the results do not support the hypothesis that changes in codons 167 and 200 of beta-tubulin isotype-1 are responsible for any resistance. PMID- 17850902 TI - Involvement of angiotensin-(1-7) in the hypothalamic hypotensive effect of captopril in sinoaortic denervated rats. AB - The role of anterior hypothalamic angiotensin-(1-7) (Ang-(1-7)) on blood pressure regulation was studied in sinoaortic denervated (SAD) rats. Since angiotensin converting enzyme inhibitors increase endogenous levels of Ang-(1-7), we addressed the involvement of Ang-(1-7) in the hypotensive effect induced by captopril in SAD rats. Wistar rats 7 days after SAD or sham operation (SO) were anaesthetized and the carotid artery was cannulated for monitoring mean arterial pressure (MAP). A needle was inserted into the anterior hypothalamus for drug administration. Intrahypothalamic administration of Ang-(1-7) (5 pmol) was without effect in SO rats but reduced MAP in SAD rats by 15.5+/-3.2 mm Hg and this effect was blocked by 250 pmol [D-Ala(7)]-Ang-(1-7), a Mas receptor antagonist. Angiotensin II (Ang II) induced an increase in MAP in both groups being the effect greater in SAD rats (DeltaMAP=15.8+/-1.4 mm Hg) than in SO rats (DeltaMAP=9.6+/-1.0 mm Hg). Ang-(1-7) partially abolished the pressor response caused by Ang II in SAD rats. Whilst the captopril intrahypothalamic injection did not affect MAP in SO animals, it significantly reduced MAP in SAD rats (DeltaMAP=-13.3+/-1.9 mm Hg). Either [D-Ala(7)]-Ang-(1-7) or an anti-Ang-(1-7) polyclonal antibody partially blocked the MAP reduction caused by captopril. In conclusion, whilst Ang-(1-7) does not contribute to hypothalamic blood pressure regulation in SO normotensive animals, in SAD rats the heptapeptide induces a reduction of blood pressure mediated by Mas receptor activation. Although Ang-(1 7) is not formed in enough amount in the AHA of SAD animals to exert cardiovascular effects in normal conditions, our results suggest that enhancement of hypothalamic Ang-(1-7) levels by administration of captopril is partially involved in the hypotensive effect of the ACE inhibitor. PMID- 17850903 TI - Chromatin dynamics during DSB repair. AB - We show that double strand breaks (DSBs) induced in chromatin of low as well as high density by exposure of human cells to gamma-rays are repaired in low-density chromatin. Extensive chromatin decondensation manifested in the vicinity of DSBs by decreased intensity of chromatin labelling, increased H4K5 acetylation, and decreased H3K9 dimethylation was observed already 15 min after irradiation. Only slight movement of sporadic DSB loci for short distances was noticed in living cells associated with chromatin decondensation around DSBs. This frequently resulted in their protrusion into the low-density chromatin domains. In these regions, the clustering (contact or fusion) of DSB foci was seen in vivo, and in situ after cell fixation. The majority of these clustered foci were repaired within 240 min, but some of them persisted in the nucleus for several days after irradiation, indicating damage that is not easily repaired. We propose that the repair of DSB in clustered foci might lead to misjoining of ends and, consequently, to exchange aberrations. On the other hand, the foci that persist for several days without being repaired could lead instead to cell death. PMID- 17850901 TI - Characterization of a novel Taenia solium oncosphere antigen. AB - Infections due to Taenia solium in humans (taeniasis/cysticercosis) remain a complex health problem, particularly in developing countries. We identified two oncosphere proteins that might protect the porcine intermediate host against cysticercosis and therefore help prevent disease in humans. One of these proteins was further identified by two-dimensional gel electrophoresis and micro sequencing. The gene encoding this protective protein was also identified, cloned and characterized. The native 31.5 kDa protein Tso31 has four variants at the cDNA level. The longest sequence from which the others seem to derive, encodes a 253 amino acid peptide. The predicted protein has a molecular weight of 25.1 kDa, one putative N-glycosylation site, two fibronectin type III domains, and one C terminal transmembrane domain. The gene structure of the protein consists of four exons and three introns. The finding of one gene and four different cDNAs for Tso31 suggests the existence of a possible mechanism of differential splicing in this parasite. The Tso31 protein is exclusive to T. solium oncospheres with a putative protein structure of an extra-cellular receptor-like protein. The Tso31 protein was expressed as a recombinant protein fused to GST and tested in a vaccine to determine its effectiveness in protecting pigs against cysticercosis. Only two pigs out of eight vaccinated were protected and although the total median number of cyst decreased in vaccinated pigs compared to controls this decrease was not statistically significant (P = 0.09). PMID- 17850905 TI - Survivability and causes of loss of broody-hen chicks on smallholder households in Bangladesh. AB - We determined the flock sizes and rates of loss caused by different factors in broody-hen chicks (BHC) up to 60 days of age on 600 randomly selected smallholdings in Bangladesh. The smallholders were beneficiaries of a village poultry production chain called 'Smallholder Livestock Development Project-2' (SLDP-2) which was undertaken with the financial assistance of the Danish International Development Agency (DANIDA). For estimating survival time of BHC, we observed chicks in 80 smallholdings. SLDP-2 aims at ameliorating poverty among women by poultry rearing at village level; in total, 104,000 key rearers, constituting 96% of all of the beneficiaries of the SLDP-2 area, were enrolled in 26 upazilas (a lower administrative unit of Bangladesh). A key rearer is a smallholder who rears at least five 'Sonali' (RIR x Fayoumi) and some indigenous (desi) chickens in a semi-scavenging system. Sonali chickens are supplied from the development project, and have higher egg production while the broodiness of the desi hens is exploited to get chicks hatched for future stocks; thus, the chicks hatched and reared to 60 days old at key rearers' households are called BHC. In this study 32% of the smallholders had BHC each month. At the beginning of a month, the median number of chicks in a flock was 8, and the mean survival time was 50.5 days. Incidence rates of loss of BHC from disease, predation, selling and slaughtering were 0.102, 0.086, 0.009 and 0.002 per chick-month at risk, respectively. The major predators were crows, mongooses and eagles with incidence rates of loss being 0.018, 0.016 and 0.010 per chick-month at risk, respectively. Colibacillosis (both single and mixed infections) contributed to the death of 21% of dead BHC collected; Newcastle disease and salmonellosis contributed to the next highest (14 and 12%) proportional mortalities. PMID- 17850906 TI - A survey on biosecurity and management practices in Belgian pig herds. AB - We surveyed Belgian pig herds to describe their biosecurity status and management practices. Our written questionnaire was sent to a stratified random sample of 609 pig farms. We achieved a 71.6% response, and 421/609 farmers (69.1%) returned questionnaires suitable for analysis. We used multiple-correspondence analysis followed by a two-step clustering procedure. Herd size, herd type and occupation (commercial or hobby herd) were used to describe different groups. We differentiated four biosecurity groups, which we interpreted as indicating low- to high-biosecurity status. Although we felt that most farms had acceptable biosecurity, few used measures such as showering (2.1%) and quarantine periods for people entering the premises (7.1%). We also found three management-practices clusters, although their interpretation was not straightforward. Despite the industrialised character of pig production in Belgium, 9.4% of pig herds were small, hobby herds that reported different biosecurity and management characteristics (such as the equipping pigs on pasture and feeding kitchen waste). PMID- 17850907 TI - Influence of dietary catechols on the growth of enteropathogenic bacteria. AB - The dietary constituents that may act, in the broadest sense, as co-factors to enable bacterial enteropathogens to replicate in gastrointestinal environments are still largely unknown. Recent work has demonstrated that certain non nutritional components of food, such as the catecholamines, can contribute to the ability of Gram-negative pathogens to replicate in iron-restrictive media that may be reflective of gastrointestinal environments. The present report examines whether other, non-catecholamine, dietary catechols, which occur widely in plant foods, can also influence enteropathogen growth in an iron-restrictive environment such as might be found in the gastrointestinal tract. In the present study, we have examined the ability of a range of catechol-rich foodstuffs, ranging from beverages (tea and coffee) to fruit and vegetable extracts, as well as purified preparations of commonly consumed dietary catechols (catechins, chlorogenic acid, caffeic acid and tannic acid), to modulate the growth of the Gram-negative enteric pathogens Escherichia coli O157:H7 and Salmonella enterica SV Enteriditis. Time-dependent growth in response to dietary catechols (0.05-5.0% v/v of beverage or fruit/vegetable extracts; 10-200 microM of purified catechols) was examined in an iron-replete, rich medium as well as in an iron-limited, basal medium designed to reflect the iron-restricted environment that is more characteristic of human and animal tissues. Results obtained in iron-replete, rich medium demonstrated dose-dependent bacteriostatic effects for certain catechols, consistent with previous studies. However, in iron-restricted medium, all of the dietary catechols produced marked growth stimulation of up to 4 logs greater than non-supplemented controls. Mechanistic studies measuring the uptake of radiolabelled (55)Fe from (55)Fe-labelled lactoferrin and transferrin in bacteria grown in the presence or absence of dietary catechols demonstrated that the ability of catechols to stimulate bacterial growth was dependent on the provision of iron from iron-sequestering glycoproteins. Urea gel analysis of transferrin incubated in the presence of the dietary catechols confirmed that these compounds were directly chelating and removing transferrin-complexed iron. Analysis using E. coli O157:H7 entA and tonB mutants further showed that a functional siderophore synthesis and uptake system was required for the growth stimulatory response. In contrast to previous studies, which have reported the anti-microbial activity of dietary catechols, the present study demonstrates that these non-nutritional components of foods can, under iron-restrictive conditions, provide iron and enable the growth of enteric bacterial pathogens. PMID- 17850908 TI - Regioselectivity of enzymatic modification of poly(methyl acrylate). AB - Enzymes are potentially useful catalysts for polymerization as well as modification of polymers. While lipases have been used previously for polymerization reactions, they have not been used for modification of polymers. In this report, lipases were used to determine regioselective modification of ester functions in a telomer of poly(methyl acrylate). The influence of chain length on the extent of transesterification of methyl acrylate telomers of DP(n) 6-50 was studied by examining the relationship between the extents of enzymic modification to other telomerization parameters. The regioselectivity was observed when the average DP(n) of telomers is in a range of 6-22. At a higher DP(n) (>22), however, the average number of reacting ester functions per telomer strongly deviated from the theoretically predicted value. This phenomenon was suspected as a result of steric hindrance caused by folding of longer telomer chains. To verify this hypothesis, acrylate telomers at a DP(n) ranging from 10 to 42 were synthesized using a shorter telogen, i.e., 2,2'-ethanedithiol. The transesterification of these telomers showed a deviation in a degree of conversion when DP(n) was greater than 10, possibly indicating the inhibition caused by steric hindrance. Therefore, regioselective modification of acrylic polymers, which is difficult to achieve by conventional chemical methods, may be accomplished enzymatically. PMID- 17850909 TI - Differential gene responses in endothelial cells exposed to a combination of shear stress and cyclic stretch. AB - We developed a compliant tube-type flow-loading apparatus that allows simultaneous application of physiological levels of shear stress and cyclic stretch to cultured cells and examined gene responses to a combination of the two forces. Human umbilical vein endothelial cells were exposed to shear stress and/or cyclic stretch for 24h, and changes in the mRNA levels of endothelin-1 (ET 1), a potent vasoconstrictor, and endothelial nitric oxide synthase (eNOS), which catalyzes the production of a potent vasodilator, NO, were determined by reverse transcriptase/PCR. Cyclic stretch (10%, 1 Hz) alone increased ET-1 mRNA levels approximately 1.6-fold, but had no effect on eNOS mRNA levels. A shear stress of 7 dynes/cm(2) and 15 dynes/cm(2) alone decreased ET-1 mRNA levels to around 83% and 61%, respectively, of the basal level, but increased the eNOS mRNA level to around 2.2-fold and 3.2-fold, respectively. When cyclic stretch and shear stress were applied simultaneously, ET-1 mRNA levels did not change significantly, but the eNOS mRNA level increased to a level equivalent to the increase in response to shear stress alone. These results indicate that the response of endothelial genes to shear stress or cyclic stretch depends on whether the two forces are applied separately or together. PMID- 17850911 TI - Glycoprotein gene relocation in rabies virus. AB - Unlike vesicular stomatitis virus, rabies virus glycoprotein gene has not been successfully relocated closer to promoter-proximal regions by reverse genetics. Here we describe an efficient system for the Evelyn-Rokitnicki-Abelseth (ERA) rabies virus with the glycoprotein gene switched with the matrix protein gene, creating a reshuffled virus ERAgm (gene order N-P-G-M-L). With the aid of an autogene plasmid, the T7 RNA polymerase containing a nuclear location signal from the SV40 large T antigen facilitated virus recovery. The rearranged ERAgm rabies virus replicated as well as the parental ERA (gene order N-P-M-G-L) virus, reaching 10(9) ffu/ml in infected BSR cells. The altered glycoprotein gene position in viral genome presented an alternative way to study the pathogenicity of rabies virus. This also provides a potential novel method for rabies vaccine development. PMID- 17850910 TI - The interaction between KSHV RTA and cellular RBP-Jkappa and their subsequent DNA binding are not sufficient for activation of RBP-Jkappa. AB - Kaposi's sarcoma-associated herpesvirus (KSHV) replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. RTA activates promoters by several mechanisms. RTA can bind to sequences in viral promoters and activate transcription. In addition, RTA interacts with the cellular recombination signal sequence-binding protein-J kappa (RBP-Jkappa), a transcriptional repressor, converts the repressor into an activator and activates viral promoters via RBP-Jkappa. Because RBP-Jkappa is required for RTA to activate lytic replication, it is important to understand how RTA cooperates with RBP-Jkappa protein to activate KSHV lytic replication program. Previously, we identified an RTA mutant, RTA-K152E, which has a defect in its direct DNA-binding activity. In this report, the effect of the mutant RTA on KSHV activation via RBP-Jkappa protein is examined. We demonstrate that RTA K152E interacts with RBP-Jkappa physically and the mutant RTA and RBP-Jkappa complex binds to target DNA properly in vivo and in vitro. However, the complex of RTA-K152E and RBP-Jkappa does not activate transcription. Furthermore, the RTA mutant (RTA-K12E) inhibits cellular Notch-mediated RBP-Jkappa activation. These data collectively suggest that the complex between KSHV RTA and cellular RBP Jkappa and the subsequent DNA binding by the complex are not sufficient for the activation of RBP-Jkappa protein. Other factor(s) whether additional cofactor(s) in the complex or the intrinsic conformation of RTA, are predicted to be required for the activation of RBP-Jkappa protein by RTA. PMID- 17850912 TI - What is the interest of rehabilitation in physical medicine and functional rehabilitation ward after total hip arthroplasty? Elaboration of french clinical practice guidelines. AB - OBJECTIVES: To develop clinical practice guidelines concerning the interest of post-operative rehabilitation in a physical medicine and functional rehabilitation (PMR) ward after total hip arthroplasty (THA). METHOD: The SOFMER (French Physical Medicine and Rehabilitation Society) methodology, associating a systematic literature review, collection of everyday clinical practice, and external review by a multidisciplinary expert panel, was used. Main outcomes were impairment, disability, medico-economic implications and postoperative complications. RESULTS: Post-operative rehabilitation in a PMR ward after THA is recommended for frail patients because of their functional status, and/or associated co-morbidities, and/or post-operative complications. For patients in whom sustained rehabilitation is not necessary, but who cannot return home, a stay in a non-specific (non-PMR) post-operative center could be recommended. Post operative rehabilitation in a PMR ward after THA could reduce the length of stay in a surgical ward and increase the functional status of patients. The total cost of the different modalities of post-operative rehabilitation after THA needs evaluation. CONCLUSION: This study suggests a value of rehabilitation in a PMR ward after THA, but good methodological quality studies are needed to evaluate the cost/benefit ratio of rehabilitation in a PMR ward after THA in the French health care system. PMID- 17850913 TI - The influence of obesity on the oxidative stress status and the concentration of leptin in type 2 diabetes mellitus patients. AB - The aim of this study was to determinate both the oxidative stress/anti-oxidative defense status and the concentration of leptin in obese, overweight and normal weight type 2 diabetes mellitus patients to seek possible association between oxidative stress and hyperleptinemia. Oxidative stress status parameters [thiobarbituric acid-reacting substances (TBARS), superoxide anion (O(2)(-)), superoxide dismutase (SOD) activity and total sulphydryl groups] and the concentration of leptin were measured in 312 subjects (178 patients and in 134 control subjects). Obese patients had a significantly higher concentration of leptin compared to obese subjects in the control population (P<0.001). They also had significantly higher plasma concentrations of TBARS, O(2)(-) and SOD activity in combination with a lower sulphydryl group concentration when compared to control subjects. Obese patients had significantly higher concentrations of both TBARS and O(2)(-) and increased SOD activity compared to normal weight patients. The odds ratio for the degree of association between oxidative stress status parameters and hyperleptinemia was strongest for TBARS [odds ratio 2.66, 95% CI (1.02-6.94), P=0.045]. The observed positive correlation between TBARS and leptin (rho=0.29, P<0.01) in obese patients suggests that increased oxidative stress and hyperleptinemia, both consequences of obesity, may play a role in type 2 diabetes mellitus development. PMID- 17850914 TI - Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): a population based study. AB - BACKGROUND/AIMS: Weight loss is considered therapeutic for patients with NAFLD. However, there is no epidemiological evidence that dietary habits are associated with NAFLD. Dietary patterns associated with primary NAFLD were investigated. METHODS: A cross-sectional study of a sub-sample (n=375) of the Israeli National Health and Nutrition Survey. Exclusion criteria were any known etiology for secondary NAFLD. Participants underwent an abdominal ultrasound, biochemical tests, dietary and anthropometric evaluations. A semi-quantitative food-frequency questionnaire was administered. RESULTS: After exclusion, 349 volunteers (52.7% male, mean age 50.7+/-10.4, 30.9% primary NAFLD) were included. The NAFLD group consumed almost twice the amount of soft drinks (P=0.03) and 27% more meat (P<0.001). In contrast, the NAFLD group consumed somewhat less fish rich in omega 3 (P=0.056). Adjusting for age, gender, BMI and total calories, intake of soft drinks and meat was significantly associated with an increased risk for NAFLD (OR=1.45, 1.13-1.85 95% CI and OR=1.37, 1.04-1.83 95% CI, respectively). CONCLUSIONS: NAFLD patients have a higher intake of soft drinks and meat and a tendency towards a lower intake of fish rich in omega-3. Moreover, a higher intake of soft drinks and meat is associated with an increased risk of NAFLD, independently of age, gender, BMI and total calories. PMID- 17850915 TI - Endotoxin measures in patients' sample: how valid are the results? PMID- 17850916 TI - Helitrons on a roll: eukaryotic rolling-circle transposons. AB - Rolling-circle eukaryotic transposons, known as Helitron transposons, were first discovered in plants (Arabidopsis thaliana and Oryza sativa) and in the nematode Caenorhabditis elegans. To date, Helitrons have been identified in a diverse range of species, from protists to mammals. They represent a major class of eukaryotic transposons and are fundamentally different from classical transposons in terms of their structure and mechanism of transposition. Helitrons seem to have a major role in the evolution of host genomes. They frequently capture diverse host genes, some of which can evolve into novel host genes or become essential for helitron transposition. PMID- 17850917 TI - A SAS macro for estimation of direct adjusted survival curves based on a stratified Cox regression model. AB - Often in biomedical research the aim of a study is to compare the outcomes of several treatment arms while adjusting for multiple clinical prognostic factors. In this paper we focus on computation of the direct adjusted survival curves for different treatment groups based on an unstratified or a stratified Cox model. The estimators are constructed by taking the average of the individual predicted survival curves. The method of direct adjustment controls for possible confounders due to an imbalance of patient characteristics between treatment groups. This adjustment is especially useful for non-randomized studies. We have written a SAS macro to estimate and compare the direct adjusted survival curves. We illustrate the SAS macro through the examples analyzing stem cell transplant data and Ewing's sarcoma data. PMID- 17850918 TI - Caveolin-1 expression is significantly associated with drug resistance and poor prognosis in advanced non-small cell lung cancer patients treated with gemcitabine-based chemotherapy. AB - Caveolin-1 was up-regulated in different drug-resistant cancer cell lines and was suggested to confer drug resistance by different mechanisms. However, the relation of caveolin-1 expression and the clinical response to chemotherapy and prognosis in non-small cell lung cancer (NSCLC) remains unknown. Total 73 NSCLC (stages IIIB and IV) patients who received gemcitabine-based chemotherapy and also had tumour specimens available before treatment were assessed for caveolin-1 expression using immunohistochemistry. Immunoreactivity of caveolin-1 was correlated with the response to chemotherapy, the clinicopathologic features, and the progression-free survival (PFS) and overall survival (OS) of all patients. Positive caveolin-1 immunostaining was found in 12 (16.4%) of the 73 patients. Eight of the twelve had disease progression and the other four patients remained stable after chemotherapy. Patients with caveolin-1 expression had a significantly lower response rate (complete or partial response, 0% versus 37.7%; P=0.01) and a poor PFS and OS (median survival time: PFS, 4.6 months versus 6.1 months, P=0.005; OS, 7.0 months versus 14 months, P<0.001) than those without caveolin-1 expression. Moreover, multivariate analyses indicated that caveolin-1 positivity was an independent prognostic factor for disease-free survival (DFS) (P=0.003) and OS (P=0.008), respectively. Caveolin-1 expression significantly correlated with drug resistance and a poor prognosis in advanced NSCLC patients treated with gemcitabine-based chemotherapy. PMID- 17850919 TI - Ensuring the right PET scan for the right patient. AB - Guidelines issued by the National Institute for Clinical Excellence (NICE) in the England and Wales recommend that rapid access to (18)F-deoxyglucose positron emission tomography (FDG-PET) is made available to all appropriate patients with non-small-cell lung cancer (NSCLC). The clinical evidence for the benefits of PET scanning in NSCLC is substantial, showing that PET has high accuracy, sensitivity and specificity for disease staging, as well as pre-therapeutic assessment in candidates for surgery and radical radiotherapy. Moreover, PET scanning can provide important information to assist in radiotherapy treatment planning, and has also been shown to correlate with responses to treatment and overall outcomes. If the government cancer waiting time targets are to be met, rapid referral from primary to secondary healthcare is essential, as is early diagnostic referral within secondary and tertiary care for techniques such as PET. Studies are also required to explore new areas in which PET may be of benefit, such as surveillance studies in high-risk patients to allow early diagnosis and optimal treatment, while PET scanning to identify treatment non responders may help optimise therapy, with benefits both for patients and healthcare resource use. Further studies are needed into other forms of lung cancer, including small-cell lung cancer and mesothelioma. In conclusion, PET scanning has the potential to improve the diagnosis and management of lung cancer for many patients. Further studies and refinement of guidelines and procedures will maximise the benefit of this important technique. PMID- 17850920 TI - Ecosystem assembly and terrestrial carbon balance under elevated CO(2). AB - Research aimed at understanding how the global carbon balance will change with elevated CO(2) has largely ignored the responses of individual species and genotypes. Yet, plant traits strongly influence the biogeochemical cycling of carbon. Here, we illustrate how differences in inter- and intraspecific responses to elevated CO(2) affect not only physiology and growth, but also higher order biotic interactions and lifetime fitness, ultimately leading to new ecosystem assemblages. We assert that the unique combination of inter- and intraspecific traits in these ecosystem assemblages ultimately determine how ecosystems respond to elevated atmospheric CO(2). Thus, the identity of species and genotypes in an ecosystem is a crucial element to consider in forecasts of global carbon balance. PMID- 17850921 TI - The synthetic melanocortin (CKPV)2 exerts broad anti-inflammatory effects in human neutrophils. AB - Natural melanocortin peptides exert broad effects on the host and they have remarkable therapeutic potential. However, successful use of melanocortins as therapeutic agents depends on the design of molecules that have more stable pharmacological profiles. The synthetic peptide (CKPV)(2), based on the C terminal sequence of alpha-melanocyte stimulating hormone (alpha-MSH), has anti tumor necrosis factor-alpha (TNF-alpha) effects in vitro and in vivo and is a promising candidate to treat inflammation. Because neutrophil activity is a major target for anti-inflammatory therapies, we determined whether (CKPV)(2) modulates human neutrophil functions in vitro. Incubation of freshly-separated human neutrophils with 10(-12)-10(-6)M (CKPV)(2) significantly inhibited activities relevant to the inflammatory reaction. Neutrophil migration toward the two chemoattractants interleukin 8 (IL-8) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) was significantly inhibited by (CKPV)(2). (CKPV)(2) also inhibited reactive oxygen intermediate (ROI) production induced by phorbol 12-myristate 13 acetate (PMA), but not that induced by fMLP. Because these effects of (CKPV)(2) were abolished by the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine (ddAdo), they appear to be cAMP-dependent. Finally, the peptide reduced lipopolysaccharide (LPS)-stimulated expression of TNF-alpha, interleukin-1beta (IL-1beta), interleukin-8 (IL-8), and intercellular adhesion molecule 1 (ICAM-1), as well as TNF-alpha protein release in cell supernatants. The data indicate that (CKPV)(2) modulates broad cAMP-dependent, anti-inflammatory pathways in human neutrophils. PMID- 17850922 TI - Neurosteroids in the fetus and neonate: potential protective role in compromised pregnancies. AB - Complications during pregnancy and birth asphyxia lead to brain injury, with devastating consequences for the neonate. In this paper we present evidence that the steroid environment during pregnancy and at birth aids in protecting the fetus and neonate from asphyxia-induced injury. Earlier studies show that the placental progesterone production has a role in the synthesis and release of neuroactive steroids or their precursors into the fetal circulation. Placental precursor support leads to remarkably high concentrations of allopregnanolone in the fetal brain and to a dramatic decline with the loss of the placenta at birth. These elevated concentrations influence the distinct behavioral states displayed by the late gestation fetus and exert a suppressive effect that maintains sleep like behavioral states that are present for much of fetal life. This suppression reduces CNS excitability and suppresses excitotoxicity. With the availability of adequate precursors, mechanisms within the fetal brain ultimately control neurosteroid levels. These mechanisms respond to episodes of acute hypoxia by increasing expression of 5alpha-reductase and P450scc enzymes and allopregnanolone synthesis in the brain. This allopregnanolone response, and potentially that of other neurosteroids including 5alpha tetrahydrodeoxycorticosterone (TH-DOC), reduces hippocampal cell death following acute asphyxia and suggests that stimulation of neurosteroid production may protect the fetal brain. Importantly, inhibition of neurosteroid synthesis in the fetal brain increases the basal cell death suggesting a role in controlling developmental processes late in gestation. Synthesis of neurosteroid precursors in the fetal adrenal such as deoxycorticosterone (DOC), and their conversion to active neurosteroids in the fetal brain may also have a role in neuroprotection. This suggests that the adrenal glands provide precursor DOC for neurosteroid synthesis after birth and this may lead to a switch from allopregnanolone alone to neuroprotection mediated by allopregnanolone and TH-DOC. PMID- 17850923 TI - Capillary liquid chromatography combined with tandem mass spectrometry for the study of neurosteroids and oxysterols in brain. AB - Neurosteroids and neurosterols are found in brain at low levels (ng/g-microg/g) against a high background of cholesterol (mg/g). As such their analysis can be challenging. Traditionally, these molecules have been analysed by gas chromatography (GC)-mass spectrometry (MS), however, the absence of molecular ions in GC-MS spectra, even from derivatised molecules, can make the discovery and identification of novel neurosteroids/sterols difficult. To avoid this scenario, liquid chromatography (LC) combined with desorption ionisation methods are employed. In this review we discuss the application of LC-MS and LC-tandem mass spectrometry (MS/MS) for the identification of neurosteroids/sterols, paying particular attention to the use of low-flow-rate LC to maximise chromatographic and mass spectrometric performance. PMID- 17850925 TI - Abeta(1-42) stimulated T cells express P-PKC-delta and P-PKC-zeta in Alzheimer disease. AB - The protein kinase C (PKC) family of enzymes is a regulator of transmembrane signal transduction, and involvement of some PKC isoforms in T-cell activation has been demonstrated. Nevertheless, very little is known about their involvement in the Amyloid beta (Abeta)-dependent molecular signals in the T lymphocytes of Alzheimer disease (AD) patients. Therefore, the aim of this study was to investigate the involvement of PKC-alpha, PKC-delta and PKC-zeta expression and activity in the signaling machinery activated in Abeta-reactive T cells, in adult healthy individuals, elderly healthy subjects, and from patients with AD. The results show that in peripheral T-cells from early AD patients, Abeta(1-42) produced a distinct subpopulation highly expressing P-PKC-delta, while in severe AD patients the same treatment induced two distinct P-PKC-delta and P-PKC-zeta T cell subpopulations. Such subpopulations were not noticeable following CD3/CD28 treatment of the same samples or after treatment of peripheral T cells from healthy adult or elderly subjects with Abeta(1-42) or with CD3/CD28. We believe that these findings may be of help in possible attempts to develop further diagnostic strategies useful for the characterization of AD. PMID- 17850926 TI - An MRI-based method for measuring volume, thickness and surface area of entorhinal, perirhinal, and posterior parahippocampal cortex. AB - Several quantitative MRI-based protocols have been developed for measuring the volume of entorhinal (ERC), perirhinal (PRC), and posterior parahippocampal (PPHC) cortex. However, since the volume of a cortical region is a composite measure, relating directly to both thickness and surface area, it would be ideal to be able to quantify all of these morphometric measures, particularly since disease-related processes, such as Alzheimer's disease (AD), may preferentially affect thickness. This study describes a novel protocol for measuring the thickness, surface area, and volume of these three medial temporal lobe (MTL) subregions. Participants included 29 younger normal subjects (ages 18-30), 47 older normal subjects (ages 66-90), and 29 patients with mild AD (ages 56-90). Cortical surface models were reconstructed from the gray/white and gray/cerebrospinal fluid boundaries, and a hybrid visualization approach was implemented to trace the ERC, PRC, and PPHC using both orthogonal MRI slice- and cortical surface-based visualization of landmarks. Anatomic variants of the collateral sulcus (CS) were classified in all 105 participants, and the relationship between CS variants and corresponding morphometric measures was examined. One CS variant - deep, uninterrupted CS not connected with nearby sulci - was the most common configuration and was associated with thinner cortex within the ERC and PRC regions. This novel protocol enables the reliable measurement of both the thickness and surface area of ERC, PRC, and PPHC. PMID- 17850924 TI - DNA methylation impacts on learning and memory in aging. AB - Learning and memory are two of the fundamental cognitive functions that confer us the ability to accumulate knowledge from our experiences. Although we use these two mental skills continuously, understanding the molecular basis of learning and memory is very challenging. Methylation modification of DNA is an epigenetic mechanism that plays important roles in regulating gene expression, which is one of the key processes underlying the functions of cells including neurons. Interestingly, a genome-wide decline in DNA methylation occurs in the brain during normal aging, which coincides with a functional decline in learning and memory with age. It has been speculated that DNA methylation in neurons might be involved in memory coding. However, direct evidence supporting the role of DNA methylation in memory formation is still under investigation. This particular function of DNA methylation has not drawn wide attention despite several important studies that have provided supportive evidence for the epigenetic control of memory formation. To facilitate further exploration of the epigenetic basis of memory function, we will review existing studies on DNA methylation that are related to the development and function of the nervous system. We will focus on studies illustrating how DNA methylation regulates neural activities and memory formation via the control of gene expression in neurons, and relate these studies to various age-related neurological disorders that affect cognitive functions. PMID- 17850927 TI - The PPAR-alpha gene in Alzheimer's disease: lack of replication of earlier association. AB - Recently, a single nucleotide polymorphism (SNP, rs1800206) in the peroxisome proliferator-activated receptor alpha (PPAR-alpha) gene has been proposed to be associated with Alzheimer's disease (AD). To verify this finding, we analyzed the PPAR-alpha SNP in 461 patients with AD and 1395 controls. In subgroups, PPAR alpha gene data could be investigated in relation to biochemical and neuropathological markers for AD. We found no significant differences in genotype or allele distributions between AD patients and controls. None of the PPAR-alpha gene variants influenced markers for AD. PMID- 17850929 TI - [Diabetes insipidus revealing chronic myelomonocytic leukemia]. AB - INTRODUCTION: Central diabetes insipidus is most frequently reported to occur after a trauma from surgery or accident. However, between 30 and 50% of cases are considered idiopathic. It's a rare complication of myelodysplastic syndrome. CASE REPORT: A 61-year-old patient presented central diabetes insipidus revealing, 17 months before, chronic myelomonocytic leukemia. Cytogenetics studies revealed monosomy 7. Acute myeloid leukemia appears 3 months after training rapid patient's death. DISCUSSION: Blood examination is necessary before to conclude idiopathic central diabetes insipidus. The discovery of chronic myelomonocytic leukemia implicates a rapid managing before its possible acute myeloid leukemia transformation. Indeed, prognosis of central diabetes insipidus and acute myeloid leukemia associated, in presence of monosomy 7, is very poor. PMID- 17850928 TI - Regenerative capacity of neural precursors in the adult mammalian brain is under the control of p53. AB - The question of whether or not stem cell loss drives aging in the brain has not been fully resolved. Here, we used mice over-expressing the short isoform of p53 (DeltaNp53 or p44) as a model of aging to gain insight into the cellular mechanisms underlying age-related functional deficits in the brain. By BrdU labeling, we observed an accelerated decline in the number of subventricular zone proliferating cells with age in p44Tg mice compared to mice with normal p53 expression. A 2-3-fold reduction in the number of slowly dividing stem cells was evident in the subventricular zone of 9-12-month-old p44Tg mice, but not in younger p44Tg mice or in normal mice. Consequently, the supply of new olfactory bulb neurons was also reduced. The number and size of neurospheres generated from subventricular zone cells from p44Tg mice was significantly reduced, and cells derived from these neurospheres had limited self-renewal and amplification capacities. At the cellular level, p44 lengthened the cell cycle and affected cell cycle reentry properties, evident by an increased proportion of cells in G0. At the functional level, p44 expression resulted in impaired olfactory discrimination in 15-16-month-old mice. This phenotype is driven by constitutive activation of p53 and constitutive expression of p21(Cip1/waf1) in neural stem cells. Our results demonstrate that p53 plays a crucial role in the maintenance of the regenerative capacity of the brain by regulating the proliferation of stem and progenitor cells. PMID- 17850930 TI - Long-lasting balanced immunity and protective efficacy against respiratory syncytial virus in mice induced by a recombinant protein G1F/M2. AB - Respiratory syncytial virus (RSV) is the primary cause of serious lower respiratory tract illness in young children. We have engineered a recombinant candidate vaccine G1F/M2, consisting of a cytotoxic T lymphocyte (CTL) epitope of RSV-M2 protein and a domain of RSV-G protein. In this study, the long-term immunogenicity and protective effect were evaluated. In G1F/M2-immunized mice, special antibodies lasted for more than 19 weeks, and the IgG1/IgG2a ratio remained a balanced level till the end of the study, suggesting mixed Th1/Th2 type of responses. Concomitantly, G1F/M2 elicited long-lived RSV-specific CTL activity that was detectable at 12 weeks after the final immunization. Stronger CTL responses were induced with immunization once more at 13 weeks after the last immunization in G1F/M2-primed mice than those in F/M2-primed mice. These results suggest that G1F/M2-induced long-lasting balanced humoral and cellular immunity responses, and immunological memory in mice. Furthermore, following RSV challenge, long-term protective efficacy was observed. RSV replication in lungs of G1F/M2-primed mice elicited also mixed Th1/Th2 responses, a property that is considered advantageous for the safety of an RSV vaccine. Therefore, G1F/M2 is a promising RSV subunit vaccine. PMID- 17850931 TI - 'It's just the normal thing to do': exploring parental decision-making about the 'five-in-one' vaccine. AB - This qualitative study explored parental decision-making about the DTaP/IPV/Hib 'five-in-one' vaccine. Semi-structured interviews were conducted with 22 parents of babies aged between 4 and 13 weeks old, recruited from four practices in southern England. A modified Grounded Theory approach identified that although parents had some concerns, most complied with the recommended programme rather than making an informed decision. Other themes related to perceived importance of immunisation; beliefs about how immunisation works; trust; perceptions of vulnerability; feelings of guilt and responsibility; and practicalities. It is important to explore how parents' attitudes change over the preschool years and to develop ways of addressing uncertainties about immunisation, including the safety of combining antigens and the need for boosters. PMID- 17850932 TI - Response to letter to the editor "Zink TK. Vaccine 2007;25(15):2766-7". PMID- 17850933 TI - Alphavirus replicon particles encoding the fusion or attachment glycoproteins of respiratory syncytial virus elicit protective immune responses in BALB/c mice and functional serum antibodies in rhesus macaques. AB - Respiratory syncytial virus (RSV) is a major cause of acute respiratory tract disease in humans. Towards development of a prophylactic vaccine, we genetically engineered Venezuelan equine encephalitis virus (VEEV) replicons encoding the fusion (Fa) or attachment (Ga or Gb) proteins of the A or B subgroups of RSV. Intramuscular immunization with a formulation composed of equal amounts of each replicon particle (3vRSV replicon vaccine) generated serum neutralizing antibodies against A and B strains of RSV in BALB/c mice and rhesus macaques. When contrasted with purified natural protein or formalin-inactivated RSV formulated with alum, the 3vRSV replicon vaccine induced balanced Th1/Th2 T cell responses in mice. This was evident in the increased number of RSV-specific IFN gamma(+) splenocytes following F or G peptide stimulation, diminished quantity of eosinophils and type 2 T cell cytokines in the lungs after challenge, and increased in vivo lysis of RSV peptide-loaded target cells. The immune responses in mice were also protective against intranasal challenge with RSV. Thus, the replicon-based platform represents a promising new strategy for vaccines against RSV. PMID- 17850934 TI - Chloride - a precursor in the formation of volatile organochlorines by forest plants? AB - Two plants, a fern (Athyrium filix-femina) and a moss (Polytrichum commune Hedw.), both commonly occurring in Northern Temperate forests, were exposed in a laboratory study to a solution of (36)Cl-chloride. The uptake of (36)Cl-chloride by the plants was investigated and the emission of volatile chlorine 36 by the plants was determined. Furthermore, speciation of the emitted volatile organochlorine compounds (VOCls) was investigated. For the fern and the moss a rapid uptake of (36)Cl-chloride was observed within a 1-h exposure period. The uptake rates for the fern and the moss, respectively, were 16 microg (36)Cl chloride g(-1) fresh weight (FW) h(-1) and 3.0 microg (36)Cl-chloride g(-1) FW h( 1), respectively. The study also suggested that after uptake by the plants (36)Cl chloride is incorporated into VOCls, which were emitted by the plants into the atmosphere. Speciation analysis of the VOCls revealed the emission of chloroform, tetrachloromethane and 1,1,1-trichloroethane. PMID- 17850935 TI - An approach to assessing the probability of unsatisfactory radon in air conditioned offices of Hong Kong. AB - In order to maintain an acceptable Indoor Air Quality (IAQ), policies, strategies and guidelines have been developed worldwide and exposure concentrations of the indoor radon have been specified. Mapping indoor radon levels for a region could be done with intensive measurements on a large number of samples. To obtain the most accurate estimate of the levels with the uncertainties specified, a statistical model has been developed in this study to predict the fractions of samples in a region having an average radon level above the action levels of 150Bqm(-3) and 200Bqm(-3). The model was based on a transformation of the variation from a small sample set of data to a population geometric distribution via an estimator, known as the 'sample correction factor'. Using a dataset from a cross-sectional measurement of indoor radon levels in 216 Hong Kong offices, where the mean was 37.2Bqm(-3) and the 68% range was from 17.3Bqm(-3) to 80.3Bqm( 3), the 'sample correction factor' was evaluated and tested by the Monte-Carlo simulations. The model estimates of the fractions above the indoor radon action levels 150Bqm(-3) and 200Bqm(-3) (1.2-7.7% and 0.4-4.1% for a sample size of 20, 2.8-5.1% and 0.8-2.4% for a sample size of 60) were demonstrated to be consistent with those determined from the dataset (3.5% and 1.4%). With the 'sample correction factor' thus quantified, it will be possible to provide the required data for the policymakers making appropriate decisions on resources and manpower management. PMID- 17850936 TI - Oral mucosal disease: recurrent aphthous stomatitis. AB - Recurrent aphthous stomatitis (RAS; aphthae; canker sores) is common worldwide. Characterised by multiple, recurrent, small, round, or ovoid ulcers with circumscribed margins, erythematous haloes, and yellow or grey floors, it usually presents first in childhood or adolescence. Its aetiology and pathogenesis is not entirely clear, but there is genetic predisposition, with strong associations with interleukin genotypes, and sometimes a family history. Diagnosis is on clinical grounds alone, and must be differentiated from other causes of recurrent ulceration, particularly Behcet disease - a systemic disorder in which aphthous like ulcers are associated with genital ulceration, and eye disease (particularly posterior uveitis). Management remains unsatisfactory, as topical corticosteroids and most other treatments only reduce the severity of the ulceration, but do not stop recurrence. PMID- 17850937 TI - An exploratory study to assess the acceptability of an antenatal quality-of-life instrument (the Mother-generated Index). AB - OBJECTIVE: to assess whether the Mother-generated Index (MGI), a validated postnatal tool, was acceptable during late pregnancy; minor modifications to the wording of the existing tool were made. The MGI allows for qualitative and quantitative assessment. DESIGN: face-to-face interviews were conducted by a single researcher using the modified MGI and the General Health Questionnaire (GHQ-30). The women wrote up to eight comments describing the most important areas of their lives, indicated whether these were positive, negative or neither, and then scored and ranked them. SETTING: two health centres in East Scotland, during a scheduled antenatal clinic visit. PARTICIPANTS: 35 women (20 nulliparous and 15 parous) in the third trimester of pregnancy. FINDINGS: interviews lasted for 15-25 mins and none of the women found the MGI difficult to complete. The mean number of comments was 4.9 (standard deviation 1.1); most were directly related to the pregnancy and some were life issues that remained pertinent during the pregnancy. Face validity was good; criterion validity could not be assessed formally, but the MGI scores and the GHQ-30 scores were well correlated (Pearson r=-0.62; p<0.001). While some comment categories were universally positive ('looking forward to baby', 'relationship with partner') and others were universally negative ('tiredness', 'aches and pains'), other categories were mixed (e.g. 'social life', 'work'). Women who expected their birth partner to be 'very helpful' had significantly higher MGI scores than women without such expectations (t=2.5, degrees of freedom=33; p=0.018). KEY CONCLUSIONS: in this comparatively small study, the MGI was acceptable to pregnant women as an assessment tool during late pregnancy. While the sample size precluded definitive statistical evaluation, the apparently logical associations between overall MGI scores and particular comments, and the good correlation between MGI and GHQ-30 scores suggest that the MGI is a feasible tool for use in late pregnancy. IMPLICATIONS FOR PRACTICE: holistic care is advocated; this subjective tool allows pregnant women to state what is most important to them, thus avoiding a 'top-down' pathological approach. The MGI can help to uncover important quality of-life issues that may not appear obvious to the midwife, and which may otherwise be missed. A larger study is required for formal evaluation of the quantitative potential of the antenatal MGI. PMID- 17850938 TI - Nausea and vomiting in pregnancy: what advice do midwives give? AB - OBJECTIVE: to determine what advice and support midwives give to women experiencing nausea and/or vomiting in pregnancy, with a particular interest in if and how herbal and alternative therapies are prescribed. DESIGN: cross sectional survey. SETTING: a public, tertiary maternity hospital in Melbourne, Australia. PARTICIPANTS: forty-nine midwives who provide antenatal care. FINDINGS: the advice most commonly given to women experiencing nausea and/or vomiting was to eat frequent small meals and snacks (91%). Other common advice was given by half the midwives or less: avoidance of fatty/spicy foods (53%); eating before rising in the morning, e.g. consumption of dry biscuits/toast (51%); and keeping hydrated (49%). Most midwives (39/46, 85%) included some form of vitamin or herbal supplement in their advice for nausea and vomiting in pregnancy; however, many were unaware of potential harmful side effects or what would constitute appropriate doses. KEY CONCLUSIONS: advice for nausea and vomiting in pregnancy was generally consistent with that documented in the literature. The findings suggest that it is likely that herbal medicines and alternative treatments are often included in common advice given for nausea and vomiting of pregnancy; however, there is little evidence to guide practice in this area. Similarly, common advice for nausea and vomiting in pregnancy is based more on anecdotal evidence than rigorous scientific evidence, highlighting a need for more research in this area. IMPLICATIONS FOR PRACTICE: it is crucial that midwives support women experiencing nausea and vomiting in pregnancy, and that the issue is not treated as merely something women need to 'cope with' as part of pregnancy. Advice given to pregnant women needs to include what is known about the safety and efficacy of various treatments in pregnancy, so they can make informed choices. There is a need for increased awareness of the issues around the safety and efficacy (or otherwise) of herbal supplements and alternative treatments when prescribed or used during pregnancy, and midwives need to be aware of the evidence for any treatment or supplement they suggest to women. Due to the small size of this study and the lack of other literature on this topic, further research would be of benefit. PMID- 17850939 TI - Biomechanical assessment of the sitting posture maintenance in patients with stroke. AB - BACKGROUND AND PURPOSE: Regaining control of sitting posture is one of the first goals in the rehabilitation of patients with stroke. So, it requires a precise quantification of this postural behaviour. The purpose of the present investigation was thus to assess postural control during sitting in people with hemiparesis through a biomechanical analysis. METHODS: Centre-of-pressure displacements were recorded by means of a force platform on which 10 patients with stroke and 10 age-matched healthy subjects were sitting. Centre-of-pressure trajectories were processed through space-time and frequency analyses. RESULTS: These centre-of-pressure displacements of the patients with stroke were characterised by an increased control for maintaining sit position and by reduced postural performance, as enlightened by the larger surfaces covered by the centre of-pressure displacements (P<.05) and increased velocities (P<.001), respectively. As shown from the frequency analysis, the impairment have affected predominantly the displacements occurring along the antero-posterior axis (P<.05). INTERPRETATIONS: The analysis of centre-of-pressure displacements during sitting posture indicates an increased postural disturbance in patients with stroke. A platform device, because of the non-invasive, easy and fast measures carried out, should thus be viewed as an attractive tool for assessing the postural dysfunctioning encountered in sat patients with stroke. This tool could also be used for evaluating, the rehabilitation process following stroke. PMID- 17850940 TI - Mobility assessment of patients with facioscapulohumeral dystrophy. AB - BACKGROUND: Facioscapulohumeral muscular dystrophy is the third most common form of inherited myopathies with a prevalence of 1:20,000. Since both muscle involvement and disease progression are heterogeneous and unpredictable, quantitative assessment tools are needed to evaluate the effects of pharmacological and physical training treatments. METHODS: The instrumented movement analysis of 12 patients with facioscapulohumeral dystrophy and 12 control subjects was conducted using a 9-camera stereophotogrammetric system and 2 force platforms. Subjects performed four tasks of different difficulties: arm movement, level walking, step ascending, and squatting. Manual muscle test, clinical severity scale and magnetic resonance imaging were used to clinically assess the patients. FINDINGS: Walking speed and centre of mass vertical displacement during squatting were reduced in patients and can be used to assess their motor capacity. Features common in the patient sample were: the reduction of shoulder range of motion, the excessive ankle plantar-flexion during walking and step ascending, and the reduction of knee flexion-extension moment during squatting. These parameters were correlated with magnetic resonance imaging results at relevant structure level and can be used to assess the corresponding body functioning. Furthermore, instrumented movement analysis was able to distinguish from normal controls also a group of patients in which clinical assessments did not show any obvious abnormalities and had been evaluated as normal. INTERPRETATION: The quantitative assessment tool devised in this study provides suitable information in terms of both motor capacity and impairment severity of patients with facioscapulohumeral dystrophy, and, thus, encouraging its use for the evaluation of therapeutic trial outcomes for this disease. PMID- 17850941 TI - POEMS syndrome. AB - POEMS syndrome is a rare paraneoplastic syndrome secondary to a plasma cell dyscrasia. Recognition of the complex of a combination of peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasmaproliferative disorder, skin changes, papilledema, extravascular volume overload (peripheral edema, pleural effusions, ascites), sclerotic bone lesions, thrombocytosis, Castleman disease is the first step in effectively managing the disease. A rise in the blood levels of vascular endothelial growth factor is usually confirmatory. More than 95% of patients will have monoclonal lambda sclerotic plasmacytoma(s) or bone marrow infiltration. In patients with a dominant sclerotic plasmacytoma, first line therapy should include radiation to the lesion. Retrospective analysis and personal experience would dictate that systemic therapy be considered for patients with diffuse sclerotic lesions or absence of any bone lesion and for those who have not demonstrated stabilization of their disease 3 to 6 months after completing radiation therapy. For those patients with diffuse disease, systemic therapy is indicated. Useful approaches include therapy with corticosteroids, low dose alkylator therapy, and high dose chemotherapy with peripheral blood stem cell transplant. Until the pathogenesis is fully understood, these are the mainstays of treatment for patients with POEMS syndrome. The role of anti-VEGF therapies, immune modulatory drugs, and proteasome inhibitors has not yet been defined, but drugs with known high rates of treatment related neuropathy should not be considered as first line therapy. PMID- 17850942 TI - Fate and behaviour of phenanthrene in the natural and artificial soils. AB - OECD artificial soil has been used routinely as a standardized substrate for soil toxicity tests. However, can be the fate, behaviour and effects of contaminants in artificial soil extrapolated to natural soils? The aim of our study was to verify this hypothesis by comparing the loss, extraction, and bioavailability of phenanthrene in three artificial and three natural soils of comparable organic carbon content. Soils were spiked with 14C-phenanthrene and total 14C-activity change, the fractions extracted by dichloromethane, 70% ethanol, and hydroxypropyl-beta-cyclodextrin, the fraction mineralized by Pseudomonas sp., and taken up by Enchytraeus albidus were measured after 1, 14, 42, and 84 d aging. The loss, extraction, biodegradation and uptake were several times lower in the artificial than natural soils and these differences increased with increasing soil-phenanthrene contact time. These results imply that artificial soil should be used cautiously for the prediction of fate and behaviour in natural soils. PMID- 17850943 TI - Staging data: theatre as a tool for analysis and knowledge transfer in health research. AB - Over the past several decades, researchers have taken an interest in theatre as a unique method of analysing data and translating findings. Because of its ability to communicate research findings in an emotive and embodied manner, theatre holds particular potential for health research, which often engages complex questions of the human condition. In order to evaluate the research potential of theatre, this article critically examines examples of evaluated health research studies that have used theatre for the purposes of data analysis or translation. We examine these studies from two perspectives. First, the literature is divided and categorized into four theatre genres: (1) non-theatrical performances; (2) ethnodramas, which can be interactive or non-interactive; (3) theatrical research based performances; and (4) fictional theatrical performances. This categorization highlights the importance of these genres of theatre and provides an analysis of the benefits and disadvantages of each, thus providing insight into how theatre may be most effectively utilized in health research. Second, we explore the efficacy of using theatre for the purposes of data analysis and knowledge transfer, and critically examine potential approaches to the evaluation of such endeavours. PMID- 17850944 TI - Do diseases have a prestige hierarchy? A survey among physicians and medical students. AB - Surveys have shown that the prestige of medical specialities is ordered hierarchically. We investigate whether similar tacit agreement in the medical community also applies to diseases, since such rankings can affect priority settings in medical practice. A cross-sectional survey was performed in three samples of physicians and medical students in Norway in 2002. A questionnaire was sent to 305 senior doctors (response rate, 79%), 500 general practitioners (response rate, 65%) and 490 final-year medical students (response rate, 64%). Outcome measures were ratings on a 1-9 scale of the prestige these respondents believed most health personnel would accord to a sample set of 38 different diseases as well as 23 medical specialities. Both diseases and specialities were clearly and consistently ranked according to prestige. Myocardial infarction, leukaemia and brain tumour were among the highest ranked, and fibromyalgia and anxiety neurosis were among the lowest. Among specialities, neurosurgery and thoracic surgery were accorded the highest rank, and geriatrics and dermatovenerology the lowest. Our interpretation of the data is that diseases and specialities associated with technologically sophisticated, immediate and invasive procedures in vital organs located in the upper parts of the body are given high prestige scores, especially where the typical patient is young or middle-aged. At the other end, low prestige scores are given to diseases and specialities associated with chronic conditions located in the lower parts of the body or having no specific bodily location, with less visible treatment procedures, and with elderly patients. PMID- 17850945 TI - Serum lipid levels and suicidality among male patients with schizoaffective disorder. AB - Suicidal behavior in schizoaffective disorder is a serious problem and suicide risk during lifetime ranges between 5%-10%. Neurobiology of suicidal behavior has not been studied sufficiently, and a high number of studies are oriented toward lipid investigation. The aim of our study was to investigate whether there were differences in the level of lipids (cholesterol, HDL-cholesterol, LDL cholesterol, triglycerides) in hospitalized suicidal (n=20) and non-suicidal (n=20) patients with schizoaffective disorder. The study also included male healthy control subjects (n=20). Hamilton Depression Rating Scale (HDRS-17), and Positive and Negative Syndrome Scale (PANSS) were used to confirm the level of psychopathology in patients with schizoaffective disorder. Severity of suicidality was measured by Scale for Suicide Ideation (SSI) at time of admission. Results of the study indicated significantly lower concentrations of cholesterol (p<0.001), LDL-cholesterol (p<0.01) and HDL-cholesterol (p<0.01). There were no differences in the number of previous hospitalization and previous suicide attempts between suicidal and non-suicidal patients (p>0.05). Duration of the illness was significantly (p<0.05) shorter in suicidal patients. Suicidal patients also had a significantly higher score on HDRS-17 (p<0.001) and PANSS (p<0.01) compared to non-suicidal patients. PMID- 17850946 TI - A case-control association study of the polymorphism at the promoter region of the DRD4 gene in Korean boys with attention deficit-hyperactivity disorder: evidence of association with the -521 C/T SNP. AB - Recent genetic studies at the 5' end of the dopamine D4 receptor (DRD4) gene have identified several polymorphisms having a possible relationship with attention deficit-hyperactivity disorder (ADHD). This study examined the association between the -521 and -376 promoter single nucleotide polymorphisms (SNPs) of the DRD4 gene and ADHD through a case-control association study in Korean boys, who constitute a single ethnic population. Ninety-four ADHD and ninety-five control boys were enrolled in this study. All of the ADHD subjects completed a comprehensive and standardized diagnostic and psychological evaluation battery including the ADHD Rating Scale-IV (ARS). Genotyping for the 2 promoter SNPs was performed. There were significant differences in the genotype and allele frequencies of the -521 C/T SNP between the ADHD and control groups (chi2=6.28, p=0.043 and chi2=6.22, p=0.013, respectively). However, the distribution of the 376 C/T genotypes and alleles were similar in the ADHD and control groups. The subtypes of ADHD were not related to either of these two SNPs. In the ADHD subjects, the -521 TT genotype group had a higher score in the inattentive subscale and a lower score in the hyperactive subscale of the parents version of ARS, although these differences did not attain statistical significance (p=0.146, p=0.082). In conclusion, there was a significant association between the -521 C/T SNP and ADHD in Korean boys. These results suggest a role of the -521 C/T SNP in the susceptibility for ADHD. PMID- 17850947 TI - [Allotransplantation, literature and movie]. AB - Writers and movie makers have always dreamed of creating a human being, changing completely a face or giving new hands. The legend of Saint Come and Saint Damien is the first example of miraculous allotransplantation. Mary Shelley's Frankenstein is considered as founder work of modern science fiction. In the 19th and 20th century, authors used the advances in medicine to imagine diabolic practitioners or brilliant surgeons to transplant entire faces or hands. Cinema uses special effects to show spectacular operations. The author presents examples of books and movies treating directly or indirectly with composite allotransplantations. PMID- 17850948 TI - Solution equilibria of the i-motif-forming region upstream of the B-cell lymphoma 2 P1 promoter. AB - The 5'-end of the P1 promoter of the B-cell lymphoma-2 (bcl-2) gene contains a highly guaninecytosine-rich region, which has a role in the regulation of bcl-2 transcription. Whereas the guanine-rich region has been the focus of recent studies, little attention has been paid to the cytosine-rich strand. Here we examine the structural transitions of the cytosine-rich sequence by means of acid base, mole-ratio and melting experiments monitored by molecular absorption, circular dichroism, and NMR spectroscopies. Two intramolecular i-motif structures have been detected in the pH range 2-7, with maximal formation at pH 4 and 6, respectively. At pH 7.6 the majority species has been associated with a hairpin involving Watson-Crick base pairs. Upon addition of the quadruplex-interacting ligand TmPyP4, bcl-2c structures at pH 6.1 and 7.6 yield identical interaction species with stoichiometries 1:2 (DNA:ligand) and logarithms of formation constant 12.4+/-0.2 and 11.7+/-0.1, respectively. The initial i-motif structure at pH 6.1 is lost upon interaction with TmPyP4. PMID- 17850949 TI - The initiating proteases of the complement system: controlling the cleavage. AB - The complement system is a vital component of the host immune system, but when dysregulated, can also cause disease. The system is activated by three pathways: classical, lectin and alternative. The initiating proteases of the classical and lectin pathways have similar domain structure and employ similar mechanisms of activation. The C1r, C1s and MASP-2 proteases have the most defined roles in the activation of the system. This review focuses on the mechanisms whereby their interaction with substrates and inhibitors is regulated. PMID- 17850950 TI - Prostate-specific antigen in the serum of women with benign breast disease. AB - OBJECTIVES: Fibrocystic mastopathy is the most common benign breast disease. Available evidence suggests that the presence of breast cysts increases the risk of breast cancer. The purpose of the study was to evaluate and compare the detection rate of total and free prostate-specific antigen (PSA) in the serum samples of healthy women and in those of women with cystic mastopathy. Moreover, we compared PSA concentrations in the serum samples of the study groups. STUDY DESIGN: The study population included 114 women with fibrocystic breast disease, with cysts measuring <10mm (Group I) and 62 with macrocysts measuring >10 mm (Group II). Forty-six healthy volunteers were enrolled in the study as a control group. We analyzed the frequency of the detection level and the mean serum concentrations of total and free PSA in women with mastopathy and in healthy participants. Total PSA (PSA-T) and free PSA (PSA-Free) were measured by an ultrasensitive fluoroimmunometric DELFIA assay (Prostatus PSA Free/Total Wallac, Turku, Finland). The detection limits was 0.01 ng/ml. RESULTS: Our results showed the statistical significance of the fact that the detection rate of free and total PSA was higher in all women with mastopathy (Group I with II) than it was in the control group. There were no differences between Group I and Group II regarding the detection rate of the two forms of antigen and between the control group and Group II in the detection rate of total PSA. We also demonstrated that the mean concentration levels of both free and total PSA were significantly higher in the serum of women with mastopathy than in the control group. CONCLUSION: These findings suggest that women with mastopathy, regardless of the size of the cysts, produce and release more PSA into the serum than women without breast pathology. The PSA may be a new marker for the assessment of benign breast disease. PMID- 17850951 TI - Adsorption kinetics of c-Fos and c-Jun to air-water interfaces. AB - The kinetics of adsorption to air-water interfaces of the biomembrane active transcription factors c-Fos, c-Jun and their mixtures is investigated. The adsorption process shows three distinct stages: a lag time, a fast pseudo zero order stage, and a halting stage. The initial stage determines the course of the process, which is concentration dependent until the end of the fast stage. We show that c-Fos has faster adsorption kinetics than c-Jun over all three stages and that the interaction between both proteins is apparent in the adsorption profiles of the mixtures. Protein molecular reorganization at the interface determines the transition to the final adsorption stage of the pure proteins as well as that of the mixtures. PMID- 17850952 TI - On how environmental stringency influences adoption of best management practices in agriculture. AB - There are relatively few Federal environmental regulations that influence agricultural production in the US. However, many local and state environmental rules may influence the management practices on US farms as might interactions between urban population centers and agricultural producers. Detailed analysis of corn farms gives insight into these relationships and suggests that stringent environmental regulations could increase the likelihood of adoption of certain conservation practices, all else being constant, but that the interaction between urban populations has less of an effect on the adoption decisions. PMID- 17850953 TI - Emergence of cortistatin as a new immunomodulatory factor with therapeutic potential in immune disorders. AB - Identification of the factors that regulate the immune tolerance and control the appearance of exacerbated inflammatory conditions is crucial for the development of new therapies of autoimmune diseases. Some neuropeptides and hormones have emerged as endogenous agents that participate in the regulation of the processes that ensure self-tolerance. Among them, cortistatin, an endogenous cyclic neuropeptide relative of somatostatin, has recently shown therapeutic potential for a variety of immune disorders. Here we examine the latest research findings, which indicate that cortistatin participates in maintaining immune tolerance in two distinct ways: by regulating the balance between pro-inflammatory and anti inflammatory factors, and by inducing the emergence of regulatory T cells with suppressive activity against autoreactive T cell effectors. PMID- 17850954 TI - Leptomeningeal disease in chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the western hemisphere, with an annual incidence of 3:100000. Commonly patients are asymptomatic but not rarely disease progression occurs in the setting of lymphadenopathy and extensive leukemic burden. Leptomeningeal involvement in patients with CLL is infrequent, with presenting symptoms of headache (23%), acute or chronic changes in mental status (28%), cranial nerve abnormalities (54%) including optic neuropathy (28%), weakness of lower extremities (23%) and cerebellar signs (18%). In this report, we discuss a CLL patient with leptomeningeal involvement, who presented with neurological symptoms as the first clinical sign, and a diagnosis of leptomeningeal was made based on CSF cytology and flow cytometry. Treatment consisted of radiation therapy and intrathecal chemotherapy with arabinoside-cytosine and systemic chemotherapy. On the basis of this patient-report together with 37 other previously reported cases, the clinical characteristics together with treatment options and outcome of leptomeningeal involvement in CLL are reviewed. Our case together with data from the literature indicate that a timely diagnosis and intensive treatment of leptomeningeal disease of CLL may lead to longstanding and complete resolution of neurological symptoms. PMID- 17850955 TI - Investigation of the role of SMN1 and SMN2 haploinsufficiency as a risk factor for Hirayama's disease: clinical, neurophysiological and genetic characteristics in a Spanish series of 13 patients. AB - OBJECTIVE: The effect of the number of copies in the SMN1 and SMN2 genes - the most extensively studied susceptibility and modifying genetic factors in adult onset motor neuron diseases - as a genetic risk factor for Hirayama's disease (HirD) has never been studied. The purpose of this study was to investigate the influence of the number of copies of the SMN1/SMN2 genes on the resulting phenotype in 13 HirD Spanish patients. PATIENTS AND METHODS: We performed a qualitative and quantitative SMN1/SMN2 gene analysis in 13 unrelated HirD patients. The phenotype-genotype correlation was investigated, paying particular attention to the effect of the SMN1/SMN2 copy number on the disease's phenotype. RESULTS: No patient had a homozygous deletion of the SMN1 or SMN2. No differences were found when comparing the SMN1 and SMN2 copy number distributions of the healthy population and HirD patients, and they do not therefore appear to be a susceptibility factor. There was also no correlation found between the number of copies of the SMN1 and SMN2 and the severity of the resulting phenotype. CONCLUSION: Our results suggest that SMN1 and SMN2 are not predisposing factors for HirD and therefore support a lack of association between these genes and the resulting phenotype. PMID- 17850956 TI - Characteristics and treatability of oil-bearing wastes from aluminum alloy machining operations. AB - Enomoto Industry Co., exclusively uses water-based cutting fluids in its aluminum alloy machining operations. Since the cost of disposal can be much greater than the cost of purchase, the treatability of spent cutting fluids is becoming a major criterion for cutting fluid selection. Samples were collected from the machining lines at Enomoto's facility to determine their characteristics and evaluate their treatability with centrifugation, chemical coagulation and electrochemical coagulation. As expected, oil and grease (O&G) and total suspended solids (TSS) are the main reasons that spent cutting fluids are prohibited from being discharged into local swage systems. The average O&G found in the spent cutting fluids is 87,354 mg/L with TSS of more than 70,000 mg/L. Both O&G and TSS are the major contributors to the high turbidity of these waste effluents. A centrifuge with a relative centrifugal force of 1318 x g, was able to reduce 60% of the turbidity. By adding the coagulant aluminum chloride, the oil-water emulsion was destabilized, and the turbidity was reduced from 3249 Formazin Attenuation Units (FAU) to around 314 FAU. With freshly generated aluminum ions in the spent cutting fluid, the electrochemical process destabilized the oil-water emulsion system. The coalesced oil droplets were adsorbed onto the highly dispersed aluminum coagulant. The oil-rich sludge that was generated in the operation was then floated to the surface, forming a blanket that was removed by skimming. The electrochemical treatment was able to reduce the turbidity to less than 14 FAU, which is the detection limit of the Hach DR/4000 UV-vis spectrophotometer. PMID- 17850957 TI - Dispersion of chitosan on perlite for enhancement of copper(II) adsorption capacity. AB - Chitosan coated perlite beads were prepared by drop-wise addition of slurry, made of chitosan dissolved in oxalic acid and perlite, to an alkaline bath (0.7 M NaOH). The beads that contained 32% chitosan enhanced the accessibility of OH and amine groups present in chitosan for adsorption of copper ions. The experiments using Cu(II) ions were carried out in the concentration range of 50-4100 mg/L (0.78-64.1 mmol/L). Adsorption capacity for Cu(II) was pH dependent and a maximum uptake of 104 mg/g of beads (325 mg/g of chitosan) was obtained at pH 4.5 when its equilibrium concentration in the solution was 812.5 mg/L at 298 K. The XPS and TEM data suggested that copper was mainly adsorbed as Cu(II) and was attached to amine groups. The adsorption data could be fitted to one-site Langmuir adsorption model. Anions in the solution had minimal effect on Cu(II) adsorption by chitosan coated perlite beads. EDTA was used effectively for the regeneration of the bed. The diffusion coefficient of Cu(II) onto chitosan coated beads was calculated from the breakthrough curve and was found to be 2.02 x 10(-8) cm(2)/s. PMID- 17850958 TI - Photocatalytic degradation of C.I. Direct Red 23 in aqueous solutions under UV irradiation using SrTiO3/CeO2 composite as the catalyst. AB - The photocatalytic degradation of C.I. Direct Red 23 (4BS) in aqueous solutions under UV irradiation was investigated with SrTiO3/CeO2 composite as the catalyst. The SrTiO3/CeO2 powders had more photocatalytic activity for decolorization of 4BS than that of pure SrTiO3 powder under UV irradiation. The effects of catalytic dose, pH value, initial concentration of dye, irradiation intensity as well as scavenger KI were ascertained, and the optimum conditions for maximum degradation were determined. Under the irradiation of a 250 W mercury lamp, the best catalytic dose was 1.5 g/L and the best pH was 12.0. Light intensity exhibited a significant positive effect on the efficiency of decolorization, whereas the initial dye concentration showed a significant negative effect. Under the conditions of a catalytic dose of 1.5 g/L, pH of 12.0, initial dye concentration of 100mg/L, light intensity of 250 W, and air flow rate of 0.15 m3/h, complete decolorization, as determined by UV-visible analysis, was achieved in 60 min, corresponding to a reduction in chemical oxygen demand (COD) of 69% after a 240 min reaction. A tentative degradation pathway based on the sensitization mechanism of photocatalysis is proposed. PMID- 17850959 TI - Bromide ion removal from contaminated water by calcined and uncalcined MgAl-CO3 layered double hydroxides. AB - A fundamental investigation on the uptake of bromide ion from contaminated water by calcined and uncalcined MgAl-CO3 layered double hydroxides (LDHs) were conducted in batch mode. The uptake capacity of calcined LDHs (CLDH) is higher than that of uncalcined LDHs, due to their different mechanisms which are confirmed by powder X-ray diffraction, FT-IR spectroscopy and TG-MS measurements. The former mechanism is based on the reconstruction of CLDH to Br-LDHs, whilst the latter is related to the surface adsorption. It has been found that the LDHs calcined at 500 degrees C with Mg/Al molar ratio of 4 represents the highest capacity to remove bromide ion from aqueous solution. The equilibrium isotherms of uptake of bromide by CLDH were well fitted by the Langmuir equation, and thermodynamic parameters such as Delta G0, Delta H0 and Delta S0 were calculated from Langmuir constants. The negative value of Delta H0 confirms the exothermic nature of adsorption. Three kinetics models were used to fit the kinetics experimental data, and it was found that the pseudo-second order kinetics model could be used to describe the uptake process appropriately. The value of Ea was calculated to be 79.9 kJ/mol, which suggests that the process of uptake bromide is controlled by the reaction rate of bromide with the CLDH rather than diffusion. PMID- 17850960 TI - Selection of surfactants for enhancing diesel hydrocarbons-contaminated media bioremediation. AB - The use of surfactants represents a valuable method to enhance the access of the microorganisms to low-soluble and recalcitrant compounds in bioremediation techniques. The choice of surfactants is the first step of feasibility studies for this application. So far, no defined procedures are present in literature to select the most suitable surfactant for the treatment of a specific contaminated site. Furthermore, the characterisation of physico-chemical parameters is important to understand the reason of successes and failures. In this paper a step procedure to select and characterise a commercial surfactant to be used in bioremediation enhancement of hydrocarbon-contaminated media was developed. Among the commercial surfactants, the procedure was applied to alkyl polyethoxylates (Brij family) and sorbitan derivates (Tween family). The selection resulted in the application of Brij 56 and Tween 80 as biodegradation-enhancer in different lab scale systems for remediation of diesel contamination. In liquid systems, Tween 80 greatly increased biodegradation of highly branched and high-molecular weight hydrocarbons, while Brij 56 enhanced degradation of highly branched hydrocarbons. Based on these results, the potential applications and the limitations of these surfactants at full scale level were estimated. PMID- 17850961 TI - Determination of heavy metals by ICP-OES and F-AAS after preconcentration with 2,2'-bipyridyl and erythrosine. AB - The applicability of 2,2'-bipyridyl and erythrosine co-precipitation method for the separation and preconcentration of some heavy metals, such as Cd, Co, Cu, Ni, Pb and Zn in actual samples for their determination by ICP-OES and F-AAS was studied. Experimental conditions influencing the recovery of the investigated metals, such as pH, molar ratio of 2,2'-bipyridyl to erythrosine, the effect of time on co-precipitation were optimized. The analytical characteristics of the method (e.g. limit of detection, sensitivity, linear range and preconcentration factor) were obtained. The limits of detection LOD (ng mL(-1)) of the ICP-OES (F AAS) method were: Cd: 4.0 (7.75), Co: 3.1 (57.2), Cu: 18 (10.3), Ni 21.3 (32.8), Pb: 35.9 (29.2) and Zn: 10.2 (6.90). The recovery of all the elements tested was more than 93%. The influence of inorganic matrix was examined. The proposed method was applied to determination of Cd, Co, Cu, Ni, Pb and Zn in vegetables and certified reference material (NCS ZC85006 Tomato). PMID- 17850962 TI - Isolation and characterization of phenanthrene-degrading strains Sphingomonas sp. ZP1 and Tistrella sp. ZP5. AB - Two bacteria strains Sphingomonas sp. strain ZP1 and Tistrella sp. strain ZP5 were identified as phenanthrene-degrading ones, based on Gram staining, oxydase reaction, biochemical tests, FAME analysis, G+C content and 16S rDNA gene sequence analysis. We isolated these two bacteria strains Sphingomonas sp. ZP1 and Tistrella sp. ZP5 from soil samples contaminated with polycyclic aromatic hydrocarbon (PAH)-containing waste from oil refinery field in Shanghai, China. Strain Sphingomonas sp. ZP1 was able to degrade naphthalene, phenanthrene, toluene, methanol and ethanol, salicylic acid and Tween 80. Moreover, it can remove nearly all the phenanthrene at 0.025% concentration in 8 days. Strain Tistrella sp. ZP5 cannot degrade phenanthrene individually but it can increase the speed of phenanthrene degradation together with ZP1. The growth conditions of strain Sphingomonas sp. ZP1 were optimized. The result also indicated that the degradation rate of phenanthrene ranged from 250 to 1000 ppm with strain ZP1 remained nearly the same, i.e., a high concentration of phenanthrene did not inhibit both the growth of microbial strains and the phenanthrene-degradation ability. Besides, the effect of non-ionic surfactants such as Brij 30, Triton X 100 and Tween 80 on the phenanthrene degradation was determined. Such two strains may be useful for bioremediation applications. PMID- 17850963 TI - Removal of lead ions in aqueous solution by hydroxyapatite/polyurethane composite foams. AB - We have prepared hydroxyapatite/polyurehthane (HAp/PU) composite foams with two different HAp contents of 20 and 50 wt.% and investigated their removal capability of Pb2+ ions from aqueous solutions with various initial Pb2+ ion concentrations and pH values of 2-6. HAp/PU composite foams synthesized exhibited well-developed open pore structures which provide paths for the aqueous solution and adsorption sites for Pb2+ ions. With increasing the HAp content in the composites, the removal capability of Pb2+ ions by the composite foams increases owing to the higher adsorption capacity, whereas the removal rate is slower due to the less uniform dispersity of HAp in composite foams. The removal rate of Pb2+ ions is also slower with increasing the initial Pb2+ ion concentration in aqueous solutions. The removal mechanism of Pb2+ ion by the composites is varied, depending on the pH value of aqueous solution: the dissolution of HAp and precipitation of hydroypyromorphite is dominant at lower pH 2-3, the adsorption of Pb2+ ions on the HAp/PU composite surface and ion exchange reaction between Ca2+ of HAp and Pb2+ in aqueous solution is dominant at higher pH 5-6, and two removal mechanisms compete at pH 4. The equilibrium removal process of Pb2+ ions by the HAp/PU composite foam at pH 5 was described well with the Langmuir isotherm model, resulting in the maximum adsorption capacity of 150 mg/g for the composite foam with 50 wt.% HAp content. PMID- 17850964 TI - Delayed hyperbaric oxygenation is more effective than early prolonged normobaric hyperoxia in experimental focal cerebral ischemia. AB - Hyperbaric (HBO) and normobaric (NBO) oxygen therapy have been shown to be neuroprotective in focal cerebral ischemia. In previous comparative studies, NBO appeared to be less effective than HBO. However, the experimental protocols did not account for important advantages of NBO in the clinical setting such as earlier initiation and prolonged administration. Therefore, we compared the effects of early prolonged NBO to delayed HBO on infarct size and functional outcome. We also examined whether combining NBO and HBO is of additional benefit. Wistar rats underwent filament-induced middle cerebral artery occlusion (MCAO) for 150 min. Animals breathed either air, 100% O(2) at ambient pressure (NBO; initiated 30 min after MCAO) 100% O(2) at 3 atm absolute (HBO; initiated 90 min after MCAO), or a sequence of NBO and HBO. Infarct volumes and neurological outcome (Garcia score) were examined 7d after MCAO. HBO (174+/-65 mm(3)) significantly reduced mean infarct volume by 31% compared to air (251+/-59 mm(3)) and by 23% compared to NBO treated animals (225+/-63 mm(3)). In contrast, NBO failed to decrease infarct volume significantly. Treatment with NBO+HBO (185+/ 101 mm(3)) added no additional benefit to HBO alone. Neurological deficit was significantly smaller in HBO treated animals (Garcia score: 13.3+/-1.2) than in animals treated with air (12.1+/-1.4), but did not differ significantly from NBO (12.4+/-0.9) and NBO+HBO (12.8+/-1.1). In conclusion, HBO is a more effective therapy than NBO in transient experimental ischemia even when accounting for delayed treatment-onset of HBO. The combination of NBO and HBO results in no additional benefit. PMID- 17850965 TI - An association study between the genetic polymorphisms within TBX1 and schizophrenia in the Chinese population. AB - The strong association between common psychiatric disorders and the 22q11.2 microdeletion suggests that haploinsufficiency of one or more genes in the region confers susceptibility to these disorders. Recent mouse studies have shown that the T-box 1 (TBX1) gene in the 22q11.2 region can cause prepulse inhibition (PPI) impairment in the heterozygous state. A study has also shown that phenotypic features of 22q11 deletion syndrome (22q11DS) were segregated with an inactivating mutation of TBX1 in one family, suggesting that the TBX1 gene plays a role in the pathogenesis of some psychiatric disorders. We performed an association study between three single nucleotide polymorphisms (SNPs) in the TBX1 gene and schizophrenia. However, we found no significant difference in the genotype or allele distributions between the 328 schizophrenics and 288 controls for any of the polymorphisms, nor was there any haplotype association. Our data suggest that the genetic polymorphisms within TBX1 do not confer an increased susceptibility to schizophrenia in the Chinese population. PMID- 17850966 TI - Transient receptor potential V2 expressed in sensory neurons is activated by probenecid. AB - Temperature-activated transient receptor potential ion channels (thermoTRPs) are known to function as ambient temperature sensors and are also involved in peripheral pain sensation. The thermoTRPs are activated by a variety of chemicals, of which specific activators have been utilized to explore the physiology of particular channels and sensory nerve subtypes. The use of capsaicin for TRPV1 is an exemplary case for nociceptor studies. In contrast, specific agents for another vanilloid subtype channel, TRPV2 have been lacking. Here, we show that probenecid is able to activate TRPV2 using electrophysiological and calcium imaging techniques with TRPV2-expressing HEK293T cells. Five other sensory thermoTRPs-TRPV1, TRPV3, TRPV4, TRPM8 and TRPA1-failed to show a response to this drug in the same heterologous expression system, suggesting that probenecid is a specific activator for TRPV2. Probenecid-evoked responses were also reproduced in a distinct subset of cultured trigeminal neurons that were responsive to 2-aminoethoxydiphenyl borate, a TRPV1-3 activator. The probenecid-sensitive neurons were mainly distributed in a medium to large-diameter population, in agreement with previous observations with TRPV2 immunolocalization. Under inflammation, probenecid elicited nociceptive behaviors in in vivo assays. These results suggest that TRPV2 is specifically activated by probenecid and that this chemical might be useful for investigation of pain related TRPV2 function. PMID- 17850967 TI - Long-range projections of Adelta primary afferents in the Lissauer tract of the rat. AB - Electrical microstimulation has been used to activate fine myelinated primary afferents running within the Lissauer tract. Stimulation of the tract at the L2/L3 border produced antidromic volleys which were recorded on the dorsal roots of more caudal spinal segments. Antidromic volleys were present in all cases for roots as far caudal as the S2 segment (L3, n=12; L4, n=6; L5, n=6; L6, n=9; S1, n=3; S2, n=6; observations in a total of 15 rats). These fibres were collaterals of primary afferents with conduction velocities in the dorsal root of up to 17.3+/-2.3 ms(-1) (mean+/-S.D., n=6; range 14-20 ms(-1)). Conduction velocities within the Lissauer tract were slower; the fastest contributing fibres had conduction velocities of 9.2+/-2.2 ms(-1) (range 6-12 ms(-1)). Lesions of the Lissauer tract caudal to the stimulation site abolished the volleys on roots lying caudal to the lesion. Most previous works have suggested that primary afferents project in the Lissauer tract for only one or two spinal segments. The present study shows that some fibres project rostrally for up to seven spinal segments (L2-S2). PMID- 17850968 TI - Does the location of the touch from the contralateral finger application affect grip force control while lifting an object? AB - It was recently shown that the magnitude of grip force used to lift and transport a hand-held object decreased if a light finger touch from the contralateral arm was provided to the wrist of the target arm [A.S. Aruin, Support-specific modulation of grip force in individuals with hemiparesis, Arch. Phys. Med. Rehabil. 86 (2005) 768-775]. In this study, we investigated whether the location of the finger touch along the target arm affects the way grip force is reduced. Subjects performed the same task of lifting and transporting an instrumented object with no involvement of the contralateral arm and when an index finger touch of the contralateral arm was provided to the wrist, thumb, mid-forearm, and the hand-held object. Grip force was reduced by approximately the same amount in all conditions with the finger touch compared to the no touch condition suggesting that its reduction was not associated with a particular point of contact of the finger with the target arm. The results of the study provide additional evidence to support of the use of a second arm in the performance of activities of daily living and stress the importance of future studies investigating contralateral arm sensory input on grip force control. PMID- 17850970 TI - The effect of a metaphylactic treatment with diclazuril (Vecoxan) on the oocyst excretion and growth performance of calves exposed to a natural Eimeria infection. AB - A multicenter field efficacy study was performed in six farms located in Belgium, France and Germany with a history of suspected coccidiosis outbreaks and the proven presence of Eimeria bovis and/or Eimeria zuernii. At each of these trial sites the calves were randomly allocated to two groups (T, treated; C, control) of similar size. In total, 231 calves were included in the study. Group T calves (n=116) were drenched with a single dose of diclazuril (Vecoxan, 1mg/kg body weight) close to the time of expected outbreak of coccidiosis (day 1 of the study period), group C calves (n=115) served as placebo-treated controls. Although E. bovis and/or E. zuernii were identified at all trial sites, clinical coccidiosis was only noted in 16% of the group C calves. At day 5 of the study period (4 days after treatment), faecal oocyst counts (opg, oocysts per gram) were substantially lower in group T ("short-term effect") compared to group C. At four trial sites, the respective values of groups T and C were significantly different (P=0.0132 to P=0.0001) in favour of group T. For the pooled data of all trial sites, this effect was highly significant (P<0.0001). The overall faecal oocyst counts from day 3 until day 21 of the study period ("Area Under the Curve") was significantly reduced in group T by 87.2-99.5% ("long-term effect") at five trial sites (P=0.0139 to P<0.0001). The pooled data revealed a highly significant effect of treatment on oocyst excretion over the observation period (P<0.0001). On five of the six trial sites, the average weight gain was higher in group T than in group C. On those trial sites, the average weight gain of group T calves exceeded that of the controls by 95-268g/day and by 2.0-6.0kg over the study period. This effect was statistically significant (P<0.01) at one trial site. Altogether the calves of group T gained on average 129g more weight daily than the controls (+2.7kg over the study period). For these pooled data, statistical analysis confirmed the positive effect of treatment of calves exposed to coccidiosis on growth performance (P=0.003). In conclusion, metaphylactic treatment with diclazuril efficiently controls coccidiosis in calves thus reducing environmental contamination with oocysts and preventing negative effects of natural exposure to coccidiosis on growth performance of calves. PMID- 17850969 TI - Evidence of altered epidermal nerve fiber morphology in adults with self injurious behavior and neurodevelopmental disorders. AB - The purpose of this preliminary study was to examine the morphology and neuropeptide density of epidermal nerve fibers quantified through skin biopsy samples from three adults with neurodevelopmental disorders and chronic self injurious behavior (SIB) secondary to mental retardation compared with non-SIB normal IQ controls. A cross-sectional design was used with 3mm punch skin biopsies collected from each participant from non-self-injurious body sites and compared with site-matched existing normal control skin samples. The study was conducted at an outpatient clinic. The primary dependent measure for the morphology analyses was the coefficient of variation (CV) to quantify the mean gap length between epidermal nerve fibers for each subject. Visual microscopic examination and quantitative analysis of the microscopy images suggested there were morphological abnormalities (increased CV) in the epidermal nerve fibers among the chronic SIB cases. Substance P (SP) fiber density was increased with 2 3 times as many fibers in SIB subjects as control subjects. Additional empirical work is needed to clarify the relation between sensory innervation of the skin and self-injury to improve assessment and treatment outcomes. PMID- 17850971 TI - Combined PCR-oligonucleotide ligation assay for detection of dairy cattle-derived Cyclospora sp. AB - A rapid and sensitive assay for the detection of Cyclospora species in dairy cattle faecal specimens has been developed. The method utilizes a nested PCR to amplify a 168-bp DNA fragment of the 18S rRNA gene of cattle-derived Cyclospora sp. and an enzyme-linked immunosorbent assay (ELISA)-based oligonucleotide ligation assay (OLA) to detect the amplified product. In this study, the OLA technique was compared with conventional gel electrophoresis for the detection of amplified product. In evaluating the PCR-OLA for Cyclospora sp. and non Cyclospora parasites, A(405) reading value for Cyclospora species was significantly higher than those for non-Cyclospora control. At known concentrations of purified amplicons from cattle-derived Cyclospora sp., the OLA was able to detect more than 0.5 ng of the amplified DNA. Of 168 clinical specimens collected from four dairy cattle farms, 6 were positive by both PCR-gel electrophoresis and the PCR-OLA procedure, and 2 were positive only by PCR-OLA, indicating the PCR-OLA procedure was more sensitive than the common way with gel electrophoresis. The results indicated that the PCR-OLA is simple, rapid and suitable in clinical detection of cattle-derived Cyclospora species. PMID- 17850972 TI - Isolation of Neospora caninum from dairy zero grazing cattle in Israel. AB - First Israeli Neospora caninum isolates were obtained from brain tissues of aborted fetuses (NcIs491 and NcIs580) from dairy farms endemic for neosporosis and maintaining cattle on zero grazing. Tissues from different parts of the fetus brains were used to infect Vero cells. Tachyzoites of N. caninum were first observed in cultures from days 30 and 32 after infection. To confirm the identity of the isolated parasites, DNA extracts from brains and cultures were tested by PCR with specific primers based on the Nc5 gene. Specific fragments were amplified by PCR from infected cultures of both fetuses on day 25. Susceptible seronegative gerbils (Meriones tristrami) were inoculated intraperitoneally with 10(3) to 10(5) tenfold dilutions of subculture tachyzoites. The inoculated gerbils developed specific antibodies to N. caninum, with end-point serum dilution of 1:4096 in the IFA assay, whereas no neurological signs or deaths were seen during 4 months of observation. PMID- 17850973 TI - Molecular diagnosis of certain nematode infections can save life and beauty, and preserve breeds of socially relevant and sporting animals. AB - The recognition that the health and welfare of some humans are improved through contact and relationships with animals is now established. Two commonly recognized assistance animals are dogs and horses. Both provide therapeutic benefits to humans with some physical and mental illnesses and both assist people with disabilities. Moreover, the public and scientific attention to the health and conservation of many animal breeds is also increasing worldwide. In the past few years, two potentially life-threatening nematode infections that can induce tumours or tumour-like masses in canids and equids, spirocercosis and draschiosis/habronemosis, respectively, are emerging in several areas of the world. This article reviews and comments how recent insights into the molecular early diagnosis of these diseases can save and preserve life, beauty and breeds of socially relevant and sporting animals. PMID- 17850974 TI - The distally based neurocutaneous sural flap: a good choice for reconstruction of soft tissue defects of lower leg, foot and ankle due to fourth degree burn injury. AB - OBJECTIVE: Debridment of fourth degree burn wound usually leads to soft tissue loss. If these wound are on distal one-third of lower leg and ankle, a simple wound changes to a complex problem. Options are available for these conditions, but each of them have advantages and disadvantages. The distally based neurocutaneous sural flap is one recent flap available for this problem which has excellent results and decreased disadvantages. METHODS: Between 2000 and 2004, all patients with acute fourth degree burns or unstable scar on the distal third of lower leg, foot or ankle that referred to our hospital were scheduled for reconstruction by sural flap. The success rate and ability of the flap to create stable durable coverage at these sites were evaluated. RESULTS: Fifteen patients from 1.5 to 75 years old were included to this study. We had excellent result with this type of flap in 14, we had 100% success rate without necrosis. Only in one patient (a 75 years old man with a history of diabetes mellitus) we had a 0.5cm necrosis of distal margin of flap which healed completely after one session of debridement. All patients were completely satisfied with this flap. CONCLUSION: Because of few drawbacks of this flap and high success rate and relative simple operative technique, we recommend sural flap as a prime option for repair of fourth degree burn, at distal leg, foot and ankle. PMID- 17850975 TI - Experimental study on repairing of nude mice skin defects with composite skin consisting of xenogeneic dermis and epidermal stem cells and hair follicle dermal papilla cells. AB - OBJECTIVE: To investigate the influence of hair follicle dermal papilla cells (DPCs) on biological features of composite skin. METHODS: In the test group, xenogeneic acellular dermal matrix was employed as the frame, DPCs were seeded on the subcutaneous side, and epithelial stem cells onto the dermal papilla side of the dermal frame so as to construct a composite skin. In the control group, there was no DPC in the frame. The two kinds of composite skin were employed to cover skin defects on the back of the nude mice. Wound healing was observed 4 weeks after grafting and area was analyzed and contraction rate was calculated. The tissue samples in the grafted area were harvested for HE staining and the state of the composite skin was observed. The stress-strain curve of the sampled skin was measured, so as to calculate the maximal breaking power of the sample. The data were collected and statistically analyzed. RESULTS: HE staining indicated that the epithelial depth was increased (more than 10 layers of cells) in test group, with only 6-7 layers in control group. The skin contraction rate in test group on the 4th week after skin grafting (3.94+/-0.013)% was much lower than that in control group (29.07+/-0.018)% (P<0.05). It was indicated by biomechanical test that the stress-strain curve of the composite skin in the test group was closer to that of normal nude mice skin in comparison to that in control group. The maximal breaking force of the composite skin in test group was (1.835+/-0.035)N (Newton), while that in control group was (1.075+/-0.065)N (P<0.01). CONCLUSION: Reconstruction of epidermis in composite skin was promoted by dermal DPCs seeded in the dermal matrix frame. As a result, there was less skin contraction in the composite skin with DPCs, so that the biological characteristics of the skin were improved. PMID- 17850976 TI - Reducing the risk of distant metastases in breast cancer patients: role of aromatase inhibitors. AB - Breast cancer continues to be one of the most prominent causes of cancer death among women worldwide. Mortality in breast cancer is most commonly caused by the occurrence of distant metastases. Thus, treatments that reduce the risk of distant metastases are likely to improve survival. The third-generation aromatase inhibitors (AIs), including anastrozole, letrozole, and exemestane, have been investigated as alternatives to tamoxifen for the adjuvant treatment of early, endocrine-responsive breast cancer. Results from several large trials have established the superior efficacy of the AIs over tamoxifen in reducing the risk of recurrences when used as upfront, switch, and extended adjuvant therapy. Here, we review recent updated results obtained with AIs as adjuvant therapy, in terms of reducing the risk of distant metastases. PMID- 17850977 TI - The neuroscience of remote spatial memory: a tale of two cities. AB - Most of our everyday activities take place in familiar environments learned in the past which we need to constantly navigate. Despite our obvious reliance on these remote spatial memories, until quite recently relatively little was known about how they are instantiated in the human brain. Here we will consider developments in the neuropsychological and neuroimaging domains where innovative methodologies and novel analysis techniques are providing new opportunities for exploring the brain dynamics underpinning the retrieval and use of remotely learned spatial information. These advances allow three key questions to be considered anew: What brain areas in humans support the retrieval and use of remotely learned spatial information? Where in the brain are spatial memories stored? Do findings relating to remote spatial memory inform theoretical debates about memory consolidation? In particular, the hippocampus, parahippocampus, retrosplenial and parietal cortices are scrutinized, revealing new insights into their specific contributions to representing spaces and places from the past. PMID- 17850978 TI - Valproic acid and other histone deacetylase inhibitors induce microglial apoptosis and attenuate lipopolysaccharide-induced dopaminergic neurotoxicity. AB - Valproic acid (VPA), a widely prescribed drug for seizures and bipolar disorder, has been shown to be an inhibitor of histone deacetylase (HDAC). Our previous study has demonstrated that VPA pretreatment reduces lipopolysaccharide (LPS) induced dopaminergic (DA) neurotoxicity through the inhibition of microglia over activation. The aim of this study was to determine the mechanism underlying VPA induced attenuation of microglia over-activation using rodent primary neuron/glia or enriched glia cultures. Other histone deacetylase inhibitors (HDACIs) were compared with VPA for their effects on microglial activity. We found that VPA induced apoptosis of microglia cells in a time- and concentration-dependent manner. VPA-treated microglial cells showed typical apoptotic hallmarks including phosphatidylserine externalization, chromatin condensation and DNA fragmentation. Further studies revealed that trichostatin A (TSA) and sodium butyrate (SB), two structurally dissimilar HDACIs, also induced microglial apoptosis. The apoptosis of microglia was accompanied by the disruption of mitochondrial membrane potential and the enhancement of acetylation levels of the histone H3 protein. Moreover, pretreatment with SB or TSA caused a robust decrease in LPS-induced pro inflammatory responses and protected DA neurons from damage in mesencephalic neuron-glia cultures. Taken together, our results shed light on a novel mechanism whereby HDACIs induce neuroprotection and underscore the potential utility of HDACIs in preventing inflammation-related neurodegenerative disorders such as Parkinson's disease. PMID- 17850979 TI - Inactivation of prefrontal cortex abolishes cortical acetylcholine release evoked by sensory or sensory pathway stimulation in the rat. AB - Sensory stimulation and electrical stimulation of sensory pathways evoke an increase in acetylcholine release from the corresponding cortical areas. The pathways by which such sensory information reaches the cholinergic neurons of the basal forebrain that are responsible for this release are unclear, but have been hypothesized to pass through the prefrontal cortex (PFC). This hypothesis was tested in urethane-anesthetized rats using microdialysis to collect acetylcholine from somatosensory, visual, or auditory cortex, before and after the PFC was inactivated by local microdialysis delivery of the GABA-A receptor agonist muscimol (0.2% for 10 min at 2 microl/min). Before PFC inactivation, peripheral sensory stimulation and ventral posterolateral thalamic stimulation evoked 60 and 105% increases, respectively, in acetylcholine release from somatosensory cortex. Stimulation of the lateral geniculate nucleus evoked a 57% increase in acetylcholine release from visual cortex and stimulation of the medial geniculate nucleus evoked a 72% increase from auditory cortex. Muscimol delivery to the PFC completely abolished each of these evoked increases (overall mean change from baseline = -7%). In addition, the spontaneous level of acetylcholine release in somatosensory, visual, and auditory cortices was reduced by 15-59% following PFC inactivation, suggesting that PFC activity has a tonic facilitatory influence on the basal forebrain cholinergic neurons. These experiments demonstrate that the PFC is necessary for sensory pathway evoked cortical ACh release and strongly support the proposed sensory cortex-to-PFC-to-basal forebrain circuit for each of these modalities. PMID- 17850980 TI - Quantitative analysis of parvalbumin-immunoreactive cells in the human epileptic hippocampus. AB - Hippocampal sclerosis is the most frequent pathology encountered in mesial temporal structures resected from patients with intractable temporal lobe epilepsy and it mainly involves hippocampal neuronal loss and gliosis. These alterations are accompanied by changes in the expression of a variety of molecules in the surviving neurons, as well as axonal reorganization in both excitatory and inhibitory circuits. The alteration of a subpopulation of GABAergic interneurons that expresses the calcium binding protein parvalbumin (PV) is thought to be a key factor in the epileptogenic process. We investigated the distribution and density of parvalbumin-immunoreactive (PV-ir) neurons in surgically resected hippocampal tissue from epileptic patients with and without sclerosis. Using quantitative stereological methods, we show for the first time that there is no correlation between total neuronal loss and PV-ir neuronal loss in any of the hippocampal fields. We also observed higher values of the total neuronal density in the sclerotic subiculum, which is accompanied by a lower density of PV-ir when compared with non-sclerotic epileptic and autopsy hippocampi. These findings suggest that, the apparently normal subiculum from sclerotic patients also shows unexpected changes in the density and proportion of PV-ir neurons. PMID- 17850981 TI - Purinergic modulation of glutamate release under ischemic-like conditions in the hippocampus. AB - The aim of the present study was to explore whether endogenous activation of different purine receptors by ATP and adenosine contributes to or inhibits excess glutamate release evoked by ischemic-like conditions in rat hippocampal slices. Combined oxygen-glucose deprivation (OGD) elicited a substantial, [Ca(2+)](o) independent release of [(3)H]glutamate, which was tetrodotoxin (1 microM) sensitive and temperature-dependent. The P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 0.1-10 microM), and the selective P2X(7) receptor antagonist Brilliant Blue G (1-100 nM), decreased OGD-evoked [(3)H]glutamate efflux indicating that endogenous ATP facilitates ischemia-evoked glutamate release. The selective A(1)-receptor antagonist 1,3 dipropyl-8-cyclopentylxanthine (DPCPX, 0.1-250 nM) and the selective A(2A) receptor antagonists 4-(2-[7-amino-2-)2-furyl(triazolo-[1,3,5]triazin-5 ylamino]ethyl)phenol (ZM241385, 0.1-20 nM) and 7-(2-phenylethyl)-5-amino-2-(2 furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH58261, 2-100 nM) decreased OGD-evoked [(3)H]glutamate efflux, indicating that endogenous adenosine also facilitates glutamate release under these conditions. The effect of DPCPX and ZM241385 was reversed, whereas the action of P2 receptor antagonists was potentiated by the selective ecto-ATPase inhibitor 6-N,N-diethyl-D-beta,gamma dibromomethyleneATP (ARL67156, 50 microM). The binding characteristic of the A(2A) ligand [(3)H]CGS21680 to hippocampal membranes did not change significantly in response to OGD. Taken together these data suggest that while A(1) receptors might became desensitized, A(2A) and P2X receptor-mediated facilitation of glutamate release by endogenous ATP and its breakdown product adenosine remains operational under long-term OGD. Therefore the inhibition of P2X/A(2A) receptors rather than the stimulation of A(1) adenosine receptors could be an effective approach to attenuate glutamatergic excitotoxicity and thereby counteract ischemia-induced neurodegeneration. PMID- 17850982 TI - Calcium-binding proteins as markers of layer-I projecting vs. deep layer projecting thalamocortical neurons: a double-labeling analysis in the rat. AB - The thalamus contains two main populations of projection neurons that selectively innervate different elements of the cortical microcircuit: the well-known "specific" or "core" (C-type) cells that innervate cortical layer IV, and, the "matrix" (M-type) cells that innervate layer I. Observations in different mammal species suggest that this may be a conserved, basic organizational principle of thalamocortical networks. Fragmentary observations in primate sensory nuclei suggest that M-type and C-type cells might be distinguished by their selective expression of calcium binding-proteins. In adult rats, we tested this proposal in a systematic manner throughout the thalamus. Applying Fast-Blue (FB) to a large swath of the pial surface in the lateral aspect of the cerebral hemisphere we labeled a large part of the M-type cell populations in the thalamus and subsequently examined FB co-localization with calbindin or parvalbumin immunoreactivity in thalamic neuron somata. FB-labeled cells were present in large numbers in the ventromedial, interanteromedial, posterior, lateral posterior and medial geniculate nuclei. Distribution of the FB-labeled neuron somata was roughly coextensive with that of the calbindin immunolabeled somata, while parvalbumin immunoreactive somata were virtually absent from dorsal thalamus. Co-localization of FB and calbindin immunolabeling ranged from >95% in the ventromedial and interanteromedial nuclei, to 30% in the dorsal lateral geniculate. Moreover, in the ventromedial and interanteromedial nuclei nearly all of the calbindin-immunoreactive neurons were also labeled with FB. In most other nuclei, however, a major population of M-type cells cannot be identified with calbindin immunolabeling. Consistent with studies in primates and carnivores, present data show that in rats M-type cells are numerous and widely distributed across the rat thalamus; however, calbindin is expressed only by a fraction, albeit a large one, of these cells. PMID- 17850983 TI - A new device for collecting saliva for cortisol determination. AB - Saliva for measurement of cortisol is generally sampled by swabbing the mouth with a cotton roll, but this method has drawbacks. In the present study, we evaluated the use of an eye sponge as an oral collection device for saliva cortisol. The eye sponge was compared with commercial cotton rolls, and tested for use in infants as well as adults. Our results show that the eye sponge has adequate cortisol recoveries, even after samples have been kept at 4-8 degrees C for up to a week. In adults, volumes of 200-250 microl are obtained without problem; although smaller volumes are obtained in young infants, they are sufficient for assays requiring only 50-100 microl of saliva. In conclusion, the eye sponge is a valid and adequate collection device for saliva cortisol. Additional advantages as compared to cotton rolls are: more comfortable sampling, tastelessness, no need to manipulate the absorbing material, and the ease with which the untrained eye can determine that enough saliva has been collected. PMID- 17850985 TI - Microbial antigen treatment in sarcoidosis--a new paradigm? AB - Increasing evidence suggests that the risk for sarcoidosis is related to exposure to microbes, particularly molds. Microbial cell wall agents, even in the absence of clinical infection, could cause a late hypersensitivity reaction leading to the formation of granulomas. A few interventions studies using antimicrobial treatment demonstrate improvement in sarcoidosis. It is suggested that diagnostic tools for the presence of microbes are used in patients with sarcoidosis and that antimicrobial treatment is considered in cases resistant to corticosteroids. PMID- 17850984 TI - Systemic growth hormone-releasing hormone (GHRH) impairs sleep in healthy young women. AB - In young male subjects peripherally administered growth hormone-releasing hormone (GHRH) enhances GH and slow wave sleep (SWS) and blunts cortisol. In contrast, in a sample of females 19-76-year old, GHRH impairs sleep and enhances adrenocorticotropic hormone (ACTH) and cortisol. In the latter study, the days of investigation were not adapted to the menstrual cycle and premenopausal and postmenopausal women as well were included. Placebo and GHRH were given during consecutive nights. In order to confirm or reject the sexual dimorphism of the effects of GHRH on sleep we applied an improved study design. In the present study we examined the effect of pulsatile administration of two dosages of GHRH (4x25 or 4x50 microg intravenously, respectively) on sleep electroencephalogram (EEG) and nocturnal hormone secretion in healthy young women according to a randomized schedule. To rule out the influence of gonadal hormone activity, the study was adapted to the phase of the menstrual cycle and was performed at 4-6th day of menstrual cycle. A carry-over effect was excluded by the interval of at least 4 weeks between examinations. Compared to placebo rapid-eye-movement sleep decreased during the first half of the night after 4x25 microg GHRH and sleep stage 4 decreased after 4x50 microg GHRH. After both dosages GH increased whereas ACTH and cortisol remained unchanged. This study confirms that systemic GHRH impairs sleep in women. PMID- 17850986 TI - Incompletely differentiated (unclassified) sex cord/gonadal stromal tumor of the testis with a "pure" spindle cell component: report of a case with diagnostic and histogenetic considerations. AB - The group of incompletely differentiated (unclassified) sex cord/gonadal stromal tumors includes rare cases with predominant spindle cell morphology. We report a rare case of a "pure" spindle cell tumor of the testis with morphological and immunohistochemical features consistent with the diagnosis of "incompletely differentiated sex cord/gonadal stromal tumor". Given the spindle cell morphology, the differential diagnosis with other benign and malignant spindle cell lesions is discussed. The concurrent presence of some morphological and immunohistochemical features of both Leydig and granulosa cell lines in the tumor suggests its origin from a stromal stem cell, possibly capable of dual differentiation, but with an arrest of maturation at an early phase of differentiation. PMID- 17850987 TI - Toxicity and anthelmintic efficacy of crude aqueous of extract of the bark of Sacoglottis gabonensis. AB - The water extract of the stem bark of Sacoglottis gabonensis was evaluated for its preliminary acute toxicity and anthelmintic efficacy against gastro intestinal nematodes of small ruminants and mice in both in vitro and in vivo studies. Intra-peritoneal administration of doses ranging from 400 to 3200 mg/kg of the aqueous stem bark extract produced varying degrees of toxicity manifested as depression, drowsiness and unsteady gait, paralysis of the hind limbs, dyspnoea, coma and death. The pathological lesions noted at necropsy were mainly congestion and edema of the lungs, bronchi and bronchioles and hepatomegally with focal necrosis of liver cells. The severity of the clinical symptoms and pathological lesions were dose-related. In the in vitro study, the extract significantly (P<0.05) reduced the hatching of strongyline nematode eggs from naturally infected small ruminants. The 100 mg/ml concentration of the extract produced the highest (94.4%) inhibition on nematode egg hatch and the result was comparable to similar effect produced by either levamisole (100% at 15 mg/ml) or albendazole (99.7% at 6.25 mg/ml). In rats experimentally infected with Heligmosomoides polygyrus, treatment with the S. gabonensis stem bark aqueous extract significantly (P<0.05) reduced adult worm burden and completely inhibited faecal egg output 5 days post treatment. PMID- 17850988 TI - Stimulation of gastric acid secretion and intestinal motility by Vernonia amygdalina extract. AB - Aqueous extract of Vernonia amygdalina infused intragastrically at a dose of 10 mg/ml to rats induced a significant increase in acid output which was reduced by, ranitidine (5 mg/kg b.w.) or atropine (1.2 microMol/kg b.w.). Moreover the extract evoked a dose-dependent contraction of the guinea pig ileum at a dose range of 0.6 mg/ml to 66 mg/ml which was inhibited by atropine (2.4 x 10(-8)-2.4 x 10(-6) M). PMID- 17850989 TI - Anti-diabetic activity of flowers of Hibiscus rosasinensis. AB - The ethanol extract of flowers of Hibiscus rosasinensis at doses of 250 mg/kg and 500 mg/kg significantly reduced the blood glucose level in both acute (1, 3, 5 h) and sub acute (1, 3, 5, 7 days) treatments. PMID- 17850990 TI - [Current practices of oocyte donation in France and Europe]. AB - This review aims to evaluate, in France, oocyte donation, an assisted reproductive technique (ART), for which 25 years of experience have shown its efficacy for the palliative treatment of infertility caused by ovarian exocrine failure. Its indications have since been expanded to cover certain genetic diseases and document failures of other ART attempts. Oocyte donation is performed within the framework of French legislation - bioethics laws 94-653 and 94-654 of 29 July 1994, and the revised bioethics law 2004-800 of 6 August 2004. Its main fundamental principles are: voluntary, free, anonymous donation, for which regulated confidentiality is assured and now - judicial decree 2004-606 of 24 June 2004 - and the synchronization of donor-recipient cycles with fresh embryo transfer in accordance with established safety procedures. According to the 2004 results of the French Group for the Study of Oocyte Donation (GEDO) for French centers actively involved in ART, the chance of pregnancy was increased to 43.4% for synchronized cycles with fresh embryo transfers versus 18.7% for deferred cycles with frozen-thawed embryos (P<0.01). In addition, follow-up studies reported the excellent family relationships and physical and psychological development of these children. The major difficulties encountered in the daily practice of oocyte donation concern the recruitment and management of donors, but also, and above all, the lack of optimal means to exercise this medical specialty, due to the lack of recognition of the organizational duties incurred, which are the cornerstone of the character-specific functioning of this type of ART. In comparison, we foresee that the discrepancies of this ART practice in Europe, with it differential facets, will lead to medical nomadism for those couples financially able to do so, when national conditions of access fail because of prohibitions but also as a consequence of insufficient means to perform the inherent tasks. Today, it seems essential to provide information on the particularity and practice of oocyte donation required for the comprehension of its obligations for the different players with the aim of obtaining the means necessary for the perpetuation of its practice. PMID- 17850991 TI - Gender differences in the comorbidity of smoking behavior and major depression. AB - OBJECTIVE: The present investigation sought to determine whether smoking behavior was associated with current or lifetime major depression and whether this association was greater in women. METHODS: Data were derived from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Wave 1, 2001 2002, n=42,565). Relationships between smoking status (daily, occasional, prior) and DSM-IV major depression (current or lifetime) by gender were assessed in terms of odds ratios using logistic regressions. RESULTS: Current (daily, occasional) and prior smoking significantly increased odds of having current or prior major depression. These associations varied as a function of gender. Women with prior smoking were at significantly higher risk of current and past depression than men (OR: 1.53 vs 1.36; 1.72 vs 1.36), as was true for current occasional (OR: 1.92 vs 1.39; 1.90 vs 1.30) and daily smoking (OR: 2.52 vs 1.95; 1.84 vs 1.48). CONCLUSIONS: The association between smoking and current or past depression is not necessarily limited to smoking that meets criteria for nicotine dependence, and is more potent in women. Smoking cessation interventions for this population should consider the role that depression may play in failure to quit and smoking relapse, particularly in women. PMID- 17850992 TI - Pathways to ecstasy use in young adults: anxiety, depression or behavioural deviance? AB - AIMS: To investigate pathways to ecstasy use disorders from pre-birth to early adulthood with particular attention to the relationship between early depressive and anxiety symptoms and later ecstasy use disorders. DESIGN: Prospective, longitudinal, population-based study started in Brisbane, South East Queensland (Australia) in 1981. Participants were 2143 young adults, followed up from pre birth to young adulthood. MEASUREMENTS: Ecstasy use disorders were assessed with the composite international diagnostic interview (CIDI-Auto). Maternal socio economic position and mental health status were assessed at baseline (antenatal visit); maternal substance use was measured at the 5-year follow-up, adolescents' behaviour at the 5- and 14-year follow-up and tobacco and alcohol use were assessed at the 14-year follow-up. FINDINGS: Eight syndrome scales of childhood behaviour were examined. After adjustment for important confounders, delinquent and aggressive behaviour in early adolescence remained significantly associated with ecstasy use disorders in early adulthood. The associations became statistically non-significant when adolescent tobacco and alcohol use were included in the model [OR=1.50 (95%CI=0.75, 3.01) for delinquency and OR=1.69 (95%CI=0.92, 3.12) for aggression]. Formal mediation tests were statistically significant (p=0.001 for delinquent behaviour and p=0.05 for aggressive behaviour). CONCLUSIONS: Our findings suggest a pathway from early deviant behaviour to ecstasy use disorders, possibly mediated through licit drug experimentation in early adolescence. PMID- 17850993 TI - HIV risk behavior among patients with co-occurring bipolar and substance use disorders: associations with mania and drug abuse. AB - BACKGROUND: Bipolar and substance use disorders frequently co-occur, and both are associated with impulsivity, impaired judgment, and risk-taking. OBJECTIVES: This study aimed to: (1) describe the rates of HIV sexual and drug risk behaviors among patients with co-occurring bipolar and substance use disorders, (2) test whether acute mania, psychiatric severity, and drug severity independently predict HIV risk, and (3) examine the relationship between specific substance dependencies and sexual risk behaviors. METHOD: Participants (N=101) were assessed for psychiatric diagnoses, substance abuse, and HIV risk behavior using structured clinical interviews and self-report questionnaires. RESULTS: The majority (75%) were sexually active in the past 6 months and reported high rates of sexual risk behaviors, including unprotected intercourse (69%), multiple partners (39%), sex with prostitutes (24%, men only), and sex trading (10%). In a multivariate linear regression model, recent manic episode, lower psychiatric severity, and greater drug severity were independent predictors of total HIV risk. Cocaine dependence was associated with increased risk of sex trading. CONCLUSIONS: Results underscore the importance of HIV prevention for this population. PMID- 17850994 TI - Necrotic enteritis-producing strains of Clostridium perfringens displace non necrotic enteritis strains from the gut of chicks. AB - We inoculated broiler chicks with mixtures of Clostridium perfringens strains to investigate the single strain dominance observed in natural cases of necrotic enteritis (NE) [Nauerby, B., Pedersen, K., Madsen, M., 2003. Analysis by pulsed field gel electrophoresis of the genetic diversity among Clostridium perfringens isolates from chickens. Vet. Microbiol. 94, 257-266]. Pre-inoculation bacteriologic culture of chick intestines yielded up to six pulsed-field gel electrophoresis (PFGE) types of C. perfringens. Birds developed typical NE lesions in response to administration (2x per day for 4 days) of a combined inoculum comprising one NE strain (JGS4143, PFGE pattern 8) and four non-NE strains (from piglet necrotizing enteritis, chicken normal flora, human gas gangrene, and bovine neonatal enteritis). After inoculation commenced, only the NE strain was recovered through the first post-inoculation day, in spite of intense efforts to recover pre-challenge flora strains and the other challenge strains. Thereafter, pre-inoculation and previously undetected PFGE types were found, and JGS4143 became undetectable. Birds inoculated simultaneously with five NE strains (from disease in chickens or turkeys, and including JGS4143) also developed lesions, but again only JGS4143 was recovered through the 1st day post challenge. At that time, birds began to be repopulated with pre-challenge PFGE types. Two NE strains (JGS4143 and JGS4064) produced bacteriocins, which inhibited each other and normal flora strains (n=17), while normal flora strains inhibited neither NE strains nor each other. Thus, it appears that naturally occurring dominance of the gut by NE strains can be reproduced experimentally. Bacteriocins directed against normal flora could possibly provide the necessary advantage, although inhibition of one NE strain by another suggests that other factors may be partially or completely responsible for the dominance. PMID- 17850995 TI - Influence of oxidative stress and metabolic adaptation on PON1 activity and MDA level in transition dairy cows. AB - Serum PON1 is a HDL-associated enzyme that protects lipoproteins, both LDL and HDL, against oxidation and it is considered as an antioxidative/anti-inflammatory component of HDL. Dairy cows are highly susceptible to oxidative stress which commonly occurs in late pregnancy and early lactation. During the transition period, increased production of reactive oxygen species is associated to processes of metabolic adaptation to a low-energy balance. We investigated serum paraoxonase-1 (PON1) activity and malondialdehyde (MDA) concentration to assess the antioxidative/prooxidative status during pregnancy and the postpartum period. In order to evaluate metabolic homeostasis, common metabolic parameters (glucose, triglyceride, total cholesterol, HDL-C and albumin concentrations) were determined as well. A significantly lower PON1 activity was found in late pregnancy and early postpartum (P<0.05) compared to the first and the second trimester of pregnancy and the mid-lactation. MDA level was significantly higher (P<0.05) in the dry period compared to pregnant lactating and postpartum cows. Serum glucose concentration (P<0.001) was lower in the early and late puerperium indicating low-energy balance in the early lactation. Serum triglyceride and albumin concentrations were lower in late puerperium (P<0.001), while total cholesterol and HDL-C were lower during the dry period (P<0.05) as well as in early postpartum (P<0.001). Significant correlations of PON1 activity with glucose (P<0.05), albumin (P<0.05), total cholesterol (P<0.001) and HDL-C (P<0.001) were also found. The observed lower serum PON1 activity and higher MDA level in late pregnancy and early postpartum could indicate a prooxidants/antioxidants imbalance influenced by reproductive stress and metabolic adaptation in the transition period of dairy cows. PMID- 17850996 TI - Selectivity of folate conjugated polymer micelles against different tumor cells. AB - Folate or folic acid has been employed as a targeting moiety of various anticancer agents to increase their cellular uptake within target cells since folate receptors are vastly overexpressed in several human tumors. In this study, a biodegradable polymer poly(d,l-lactide-co-glycolide)-poly(ethylene glycol) folate (PLGA-PEG-FOL) was used to form micelles for encapsulating anticancer drug doxorubicin (DOX). The drug loading content, encapsulation efficiency and in vitro release were characterized. To evaluate the targeting ability of the folate conjugated micelles, the cytotoxicity and cellular uptake of DOX-loaded micelles on three cancer cell lines with different amount of folate receptors (KB, MATB III, C6) and normal fibroblast cells (CCL-110) were compared. The cytotoxicity of PLGA-PEG-FOL micelles to cancer cells was found to be much higher than that of normal fibroblast cells, demonstrating that the folate conjugated micelles has the ability to selectively target to cancer cells. For normal cells, the cellular uptake of PLGA-PEG-FOL micelles was similar to PLGA-PEG micelles without folate conjugation, and was substantially lower than that of cancer cells. In addition, the cell cycle analysis showed that the apoptotic percentage of normal fibroblasts was substantially lower compared with the cancer cells after exposing to DOX-loaded PLGA-PEG-FOL micelles. An optimal folate amount of approximately 40 65% on the micelles was found to be able to kill cancer cells but, at the same time, to have very low effect to normal cells. PMID- 17850997 TI - Zero-order delivery of a highly soluble, low dose drug alfuzosin hydrochloride via gastro-retentive system. AB - A composite gastro-retentive matrix for zero-order delivery of highly soluble drug alfuzosin hydrochloride (10mg) has been designed and characterized. Two systems containing polyethylene oxide (PEO), hydroxypropylmethylcellulose (HPMC), sodium bicarbonate, citric acid and polyvinyl pyrrolidone were dry blended and compressed into triple layer and bi-layer composite matrices. Dissolution studies using the USP 27 paddle method at 100 and 50rpm in pH 2.0 and 6.8 were performed using UV spectroscopy at 244nm, with automatic sampling over a 24h period using a marketed product as a reference to calculate the "f(2)" factor. Textural characteristics of each layer, the composite matrix as a whole, and floatation potential were determined under conditions similar to dissolution. Percent matrix swelling and erosion along with digital images were also obtained. Both systems proved to be effective in providing prolonged floatation, zero-order release, and complete disentanglement and erosion based on the analysis of data with "f(2)" of 68 and 71 for PEO and HPMC based systems, respectively. The kinetics of drug release, swelling and erosion, and dynamics of textural changes during dissolution for the designed composite systems offer a novel approach for developing gastro-retentive drug delivery system that has potential to enhance bioavailability and site-specific delivery to the proximal small intestine. PMID- 17850998 TI - Click-evoked otoacoustic emissions (CEOAEs) recorded from neonates under 13 hours old using conventional and maximum length sequence (MLS) stimulation. AB - Maximum length sequence (MLS) stimulation allows click evoked otoacoustic emissions (CEOAEs) to be averaged at very high stimulation rates. This enables a faster reduction of noise contamination of the response, and has been shown to improve the signal-to-noise ratio (SNR) of CEOAEs recorded from adult subjects. This study set out to investigate whether MLS averaging can enhance the SNR of CEOAEs recorded in newborns within the first day after birth, and so improve the pass rates for OAE screening in this period, when false alarm rates are very high. CEOAEs were recorded in a neonatal ward from 57 ears in 37 newborns ranging from 6 to 13h old, using both conventional (50/s) and high rate (5000/s) MLS averaging. SNR values and pass rates were compared for responses obtained within equal recording times at both rates. MLS averaging produced an SNR improvement of up to 3.8dB, with the greatest improvement found in higher frequency bands. This SNR advantage resulted in pass rate improvement between 5% and 10%, depending on pass criterion. A significant effect of age was found on both SNR and pass rate, with newborns between 6 and 10h old showing significantly lower values than those tested between 10 and 13h after birth, as well as a much greater improvement due to MLS averaging. The findings show that MLS averaging can reduce false alarm rates by up to 15% in very young neonates in a neonatal ward setting. PMID- 17850999 TI - Auditory brainstem activity in children with 9-30 months of bilateral cochlear implant use. AB - Bilateral cochlear implants aim to restore binaural processing along the auditory pathways in children with bilateral deafness. We assessed auditory brainstem activity evoked by single biphasic pulses delivered by an apical or basal electrode from the left, right and both cochlear implants in 13 children. Repeated measures were made over the first 9-30 months of bilateral implant use. In children with short or long periods of unilateral implant use prior to the second implantation, Wave eV of the auditory brainstem response was initially prolonged when evoked by the naive versus experienced side. These differences tended to resolve in children first implanted <3 years of age but not in children implanted at older ages with long delays between implants. Latency differences were projected to persist for longer periods in children with long delays between implants compared with children with short delays. No differences in right versus left evoked eV latency were found in 2 children receiving bilateral implants simultaneously and their response latencies decreased over time. Binaural interaction responses showed effects of stimulating electrode position (responses were more detectable when evoked by an apical than basal pair of implant electrodes), and duration of delay between implants (measured by latency delays). The trends shown here suggest a negative impact of unilateral implant use on bilateral auditory brainstem plasticity. PMID- 17851000 TI - Glandular hamartoma of the larynx: report of a case. AB - Glandular hamartoma is an extremely rare congenital malformation of the larynx. Presenting symptoms result from airways obstruction and may include slowly rising respiratory distress, stridor, changes in voice, eating and activity levels. Management consists in local mass excision with a good functional result and prognosis. Recurrences are usually associated with incomplete removal. We present a 3-month-old infant with a history of stridor and respiratory distress caused by a firm 0.4cm wide and 1.4cm long mass arising in the supraglottic region and detected with endoscopic approach. The lesion was excised endoscopically with an uneventful postoperative course and an excellent long-term prognosis. Histopathologically the lesion consisted of mature tissues with abnormal growth and disorganized architecture, chiefly composed of mature glandular structures, smooth muscular fibers, mature fat, surrounded by fibrous stroma and covered by typical squamous epithelium. The aim of our report is to underline how this condition must be considered by physicians, paediatricians and anaesthetists as an important cause of airway obstruction. PMID- 17851001 TI - Management of thyroid gland invasion in laryngopharyngeal cancer. AB - BACKGROUND AND OBJECTIVES: The incidence of thyroid gland involvement in laryngopharyngeal cancer ranges from 0 to 23%. Therefore, ipsilateral hemithyroidectomy and isthmusectomy are routinely performed with total laryngectomy in many clinics. Hemithyroidectomy causes hypothyroidism in 63% of patients, and if combined with radiotherapy, the incidence increases to 89% of patients. But there is no consensus about using thyroid surgery in the treatment of laryngopharyngeal cancer. The purpose of this study was to identify criteria to use in the decision of whether, in cases of laryngopharyngeal cancer, hemithyroidectomy should be performed with total laryngectomy. MATERIALS AND METHODS: The study group consisted of 28 patients with a mean age of 63.2 years (range 42-77 years). All patients were treated by thyroidectomy with total laryngectomy. We evaluated the incidence of thyroid gland invasion, clinical predisposing factors, pathologic features, and prognosis in cases of laryngopharyngeal cancer. RESULTS: The incidence of thyroid gland invasion was 14% (4/28). Subglottic extension was the only statistically significant factor in thyroid invasion. All cases of laryngopharyngeal cancer that invaded the thyroid gland had vocal cord fixation, anterior commissure invasion, and were advanced stage. The most common mechanism of spread to the thyroid was by direct extension through thyroid cartilage and anterior commissure. While the prognosis of patients with thyroid gland invasion was worse than that of patients with no invasion, the difference was not statistically significant. CONCLUSION: Prophylactic thyroidectomy should be performed in cases of laryngopharyngeal cancer where there is subglottic extension of the tumor. PMID- 17851002 TI - Synchronous bilateral carotid body tumor and vagal paraganglioma: a case report and review of literature. AB - We present a case of synchronous bilateral carotid body tumor and vagal paraganglioma in a 49-year-old man who presented with 3 months history of tenderness and palpable neck masses bilaterally. An encapsulated mass which was thought to be a carotid body tumor and an incidental 3 cm x 2 cm, 5 cm x 1 cm, 5 cm mass which seemed to be originated from vagus nerve were dissected from the left side. Pathology revealed carotid body tumor and vagal paraganglioma. Six months after the first operation, the carotid body tumor on the right side was totally excised. A discussion of this case is followed by a review of the literature surrounding this rare clinic and pathological entity. PMID- 17851004 TI - Middle ear hemangiona: a case report. AB - A middle ear hemangioma was detected in a 51-year-old man who suffered from fullness and hearing loss in the left ear. This case is presented with a review of the relevant literature. The mass was surgically resected for diagnostic and therapeutic reasons, and pathologic examination revealed a benign hemangioma. The CT, MRI, angiography, and light microscopy findings of the tumor are documented and compared with those a glomus tumor. The significance of this diagnosis is also discussed. PMID- 17851003 TI - First-bite syndrome: a review of 29 patients with parapharyngeal space tumor. AB - OBJECTIVE: The aim of this study is to clarify the etiology of first-bite syndrome. METHODS: A total of 29 consecutive patients treated with a surgical resection for parapharyngeal space tumor between April 1999 and April 2005 were retrospectively reviewed. RESULTS: Nine cases of first-bite syndrome were developed. Eight of those patients had undergone surgical ablation of the cervical sympathetic chain and/or external carotid artery. In two patients who underwent ablation of the sympathetic chain but in whom first-bite syndrome did not develop, the superior cervical ganglion was probably preserved. CONCLUSION: The present findings strongly indicate that loss of sympathetic innervation to the parotid gland from the superior cervical ganglion causes first-bite syndrome. They also suggest that some residual or autonomous activity of the superior cervical ganglion could prevent development of first-bite syndrome even if the lower sympathetic trunk was ablated. PMID- 17851005 TI - Penetrating air gun wound in the neck. AB - BACKGROUND: Injuries from air weapons can be serious and potentially fatal. It has been estimated that up to four million such weapons exist in UK households. CASE REPORT: We present the case of an 8-year-old boy who sustained a penetrating neck wound from an air gun. Use of the flexible laryngoscope in the resuscitation room allowed localization of the gun pellet in the airway. CONCLUSIONS: This approach, combined with careful clinical assessment led to immediate removal by direct laryngoscopy, thus avoiding the morbidity of unnecessary surgical exploration. PMID- 17851006 TI - [Infrarenal aortic pseudo-aneurism due to Coxiella burnetii]. AB - Peripheral vascular expressions of Coxiella burnetti Q fever are not well known. Endocarditis with negative blood culture is the most frequent clinical presentation of chronic Q fever. To date, very few cases of aneurisms or vascular grafts infections have been described. We report the case of a 54-year-old man who presented an infrarenal abdominal aorta infection, leading to a giant pseudo aneurismal formation. Blood serology and polymerase chain reaction amplification identified C. burnetti from the aortic thrombus after pseudo aneurism surgery. The treatment associated infrarenal abdominal aorta repair using a cryopreserved aorta allograft, and long-term antibiotic therapy. PMID- 17851007 TI - [Colorectal cancers in Martinique: incidence and mortality rates over a period of 20 years]. AB - BACKGROUND: Colorectal cancer is the second leading cause of cancer death in Western countries, with an incidence progressively increasing in developing countries. Worldwide, colorectal cancer is the second and third leading cause of death by cancer in females and males respectively. According to the Martinique Cancer Register data, colorectal cancer is the second leading cause of death by cancer in women, and the fourth in men. Colorectal cancer exhibits a variable distribution worldwide. This study was conducted to observe variations in colorectal incidence and mortality rates observed over a twenty-year period. Such data will be useful for monitoring changing trends related to onset of an organized screening program. METHOD: Patients with colorectal cancer diagnosed from 1981 to 2000 in Martinique were included in this study. Data are obtained from the Martinique Cancer Register. RESULTS: The incidence of colorectal cancer in Martinique (16/100,000 and 17/100,000 in the female and male population respectively in the year 2000) is intermediary compared with other countries worlwide. There is a current trend towards increased incidence and mortality. The incidence has increased for cancers localized in the proximal colon, the sigmoid colon and the rectum. CONCLUSION: The increasing incidence of colorectal cancer in all localisations raises concern in Martinique. A significant predominance of colorectal cancer incidence among the male population in Martinique was not observed. Gender and age do not appear to imply any preferential localisation of colorectal cancer. PMID- 17851008 TI - [Determination of vital status by linkage of anonymised hospital and national mortality data]. AB - BACKGROUND: A subject's vital status is essential for epidemiological studies. This information may be obtained for large numbers of patients with different methods, but these are often expensive. This study was aimed at assessing the performance of patient vital status determination using a record linkage method between hospital data and national mortality data once the information was made anonymous in compliance with French legislation. METHODS: All patients hospitalised in the Gustave-Roussy Institute, a cancer center in Villejuif France, were eligible for inclusion if they lived in France (mainland or Overseas Departments). The study cohort included patients admitted for the first time for malignant or suspected malignant-tumor during the period 1998-2000. Nominal data from the Gustave Roussy Institute hospital files as well as from the French National Institute of Statistics and Economic Studies (INSEE) mortality databases were then anonymised using irreversible hash coding. Once anonymised, the Gustave Roussy Institute and INSEE mortality databases were linked using the Jaro probabilistic method. Record linkage involved the following variables: birth name, first given name and birth date, along with the INSEE code of birth place. RESULTS: 10,089 patients were included. The linkage record results were very satisfactory for all the patients included; the percentage of those properly classified was 97.2%, sensitivity was 94.8% and specificity 99.5%. The performance of the probabilistic record linkage method on anonymised data was very satisfactory (sensitivity 96.8% and specificity 99.8%) for determining vital status for patients born in France, suffering from cancer and in-patients at the Institute Gustave-Roussy. Results were inferior for patients born abroad (sensitivity 82.8% and specificity 97.7%) but the method achievements may be enhanced by additional manual validation steps. CONCLUSION: Probabilistic linkage on data rendered anonymous enables to obtain information on vital status for a great number of subjects at low cost, in compliance with French legislation. PMID- 17851009 TI - [Cell Phones and Risk of brain and acoustic nerve tumours: the French INTERPHONE case-control study]. AB - BACKGROUND: Use of cell phones has increased dramatically since 1992 when they were first introduced in France. Certain electromagnetic fields (at extremely low frequency) have been recognized as possibly carcinogenic by the International Agency for Research on Cancer. Given the use of radiofrequency technology in cell phones, the rapid increase in the number of cell phones has generated concerns about the existence of a potential health hazard. To evaluate the relationship between the use of cell phones and the development of tumors of the head, a multicentric international study (INTERPHONE), coordinated by the International Agency for Research on Cancer, was carried out in 13 countries. This publication reports the results of the French part of the INTERPHONE study. METHODS: INTERPHONE is a case-control study focused on tumors of the brain and central nervous system: gliomas, meningiomas and neuromas of cranial nerves. Eligible cases were men and women, residents of Paris or Lyon, aged 30-59, newly diagnosed with a first primary tumor between February 2001 and August 2003. The diagnoses were all either histologically confirmed or based upon unequivocal radiological images. Controls were matched for gender, age (+/-5 years) and place of residence. They were randomly drawn from electoral rolls. Detailed information was collected for all subjects during a computer-assisted face-to-face interview. Conditional logistic regression was used to estimate the odds ratio (OR) for an association between the use of cell phones and risk of each type of cancer. RESULTS: Regular cell phone use was not associated with an increased risk of neuroma (OR=0,92; 95% confidence interval=[0.53-1.59]), meningioma (OR=0,74; 95% confidence interval=[0.43-1.28]) or glioma (OR=1.15; 95% confidence interval=[0.65-2.05]). Although these results are not statistically significant, a general tendency was observed for an increased risk of glioma among the heaviest users: long-term users, heavy users, users with the largest numbers of telephones. CONCLUSION: No significant increased risk for glioma, meningioma or neuroma was observed among cell phone users participating in Interphone. The statistical power of the study is limited, however. Our results, suggesting the possibility of an increased risk among the heaviest users, therefore need to be verified in the international INTERPHONE analyses. PMID- 17851010 TI - Norepinephrine treatment and aging lead to systemic and intracellular oxidative stress in rats. AB - Reactive oxygen species (ROS) play important roles in cellular senescence and organismic aging. Furthermore, they have been implicated in some of the adverse effects of chronic stress due to elevated peripheral levels of catecholamines. Here, we applied three different techniques to individually compare the systemic and intracellular oxidative stress in aged (23 months) and young (5 months) Sprague-Dawley rats, and in young rats treated for 12 or 24 h with norepinephrine (NE). Thiol groups of blood serum proteins (RSH) were determined by means of Ellman's reaction. Intracellular ROS were assessed in spleen cells and peripheral blood lymphocytes (PBL) by carbonylation of cellular (spleen) proteins as determined by immunoblotting (Oxyblot) and/or by means of 2',7' dichlorofluorescein (DCF) fluorescence. As compared to the young, untreated controls, both old rats and NE treated young rats showed similarly lowered RSH values paralleled by elevated intracellular ROS levels or enhanced Oxyblot signals. Individual RSH values were highly significantly, negatively correlated with respective Oxyblot data as well as with DCF fluorescence. The results confirm the roles of ROS in aging and adrenergic stress in the rat model, and suggest that the decrease in RSH of blood serum may be taken as a valid indicator for the enhanced oxidative stress in lymphocytes. PMID- 17851011 TI - Late enhancement using multidetector row computer tomography: a feasibility study with low dose 80 kV protocol. AB - AIMS: Detecting stenoses of coronary arteries with multidetector row computer tomography (MDCT) is a well feasible non-invasive method. However, there is still the problem of deciding whether a stenosis is hemodynamically relevant or not. Objective of the present study was to validate the feasibility of a low dose protocol for MDCT using 80 kV for detecting late enhancement. METHODS AND RESULTS: Using a Alderson-Rando Phantom evaluation of the effective dose of this LE protocol was performed. Ten patients (six male, four female, mean age 61) with known coronary artery disease and scheduled for a conventional coronary angiogram in our facility were subsequently recruited. All patients underwent CT angiography (CTA) 1 day prior to magnetic resonance imaging. Five minutes after the application of 100ml contrast agent for the CTA scan, a low dose late enhancement scan (80 kV, 400 mA s maximum, ECG pulsed scan, 64 mm x 0.6mm collimation, 0.33 s tube rotation) was performed. Phantom dose measurements showed an effective dose for this protocol of 1.19 mSv (male) and 1.61 mSv (female). Fifty-six percent (5/9) of the patients showed a late enhancement on the MRI scan. Three transmural late enhancements and all four negative findings were correctly identified by CT. This represents a sensitivity of 78% (3/5), specificity of 100% (3/3), NPV of 100% (4/4) and a PPV of 97%. CONCLUSION: We were able to show that the low dose protocol is feasible and, furthermore, preliminary results look promising. PMID- 17851012 TI - Vascular emergencies in liver trauma. AB - The use of CT in the diagnosis and management of liver trauma is responsible for the shift from routine surgical versus non-surgical treatment in the management of traumatic liver injuries, even when they are of high grade. The main cause of complication and of death in liver trauma is related to vascular injury. The goal of this review focussed on the vascular complications of liver trauma is to describe the elementary lesions shown by CT in liver trauma including laceration, parenchymal hematoma and contusions, partial devascularisation, subcapsular hematomas, hemoperitoneum, active bleeding, pseudoaneurysm of the hepatic artery, bile leak, and periportal oedema, to illustrate the possible pitfalls in CT diagnosis of liver trauma and to underline the key-points which may absolutely be present in a CT report of liver trauma. Then we will remind the grading system based on the CT features and we will analyze the interest and limitations of such grading systems. Last we will discuss the diagnostic strategy at the early phase in patients with suspected liver trauma according to their clinical conditions and underline the conditions of arterial embolization, and then we will discuss the diagnosis strategy at the delayed phase according to the suspected complications. PMID- 17851013 TI - Estimation of the transition temperature for an enantiotropic polymorphic system from the transformation kinetics monitored using Raman spectroscopy. AB - Polymorphism is a frequently encountered phenomenon in organic materials and is particularly important for pharmaceuticals. For enantiotropically related polymorphs, one important property of the polymorphic pair is the thermodynamic transition temperature. The transition temperature is sometimes difficult to determine experimentally due to the rapid transformation between the two polymorphic forms in solution. Due to its relatively rapid spectral acquisition rate, as well as the possibility of in-line monitoring, Raman spectroscopy is ideally suited to monitoring the kinetics of transformation between different solid-state forms. In this study, it was demonstrated that the transition temperature could be estimated from polymorphic transformation profiles obtained from real-time in situ Raman data. Using this method, the estimated transition temperature for flufenamic acid was in good agreement with the previously published value. These results suggest that Raman spectroscopy may be a useful method to determine transition temperatures in systems not amenable to other methods. PMID- 17851014 TI - Study of ascorbic acid interaction with hydroxypropyl-beta-cyclodextrin and triethanolamine, separately and in combination. AB - Complexation between ascorbic acid, hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and triethanolamine (TEA), separately and in combination, was studied in solution and solid state. The freeze-drying method was used to prepare solid complexes, while physical mixtures being obtained by simple blending. These complexes were characterized in the solid state using differential scanning calorimetry (DSC) and infrared spectroscopy (IR). Nuclear magnetic resonance spectroscopy ((1)H and (13)C NMR) was used in aqueous solutions to obtain information about the mode of interaction. The degradation rate of each complex in solution was determined, and the stability constant of the complexes and the degradation rate of the ascorbic acid within the complexes were obtained. NMR studies provided clear evidence of partial inclusion into the HP-beta-CD cavity, but the stability constant value was very small indicating a weak host-guest interaction. The influence of complexation on the degradation rate of ascorbic acid was evaluated, and the data obtained showed a pronounced enhancement of aqueous stability with the TEA association complex, while this effect was lower with the HP-beta-CD inclusion complex. NMR experiments showed evidence of the formation of aggregates. PMID- 17851015 TI - Development of an instrument to measure seniors' patient safety health beliefs: the Seniors Empowerment and Advocacy in Patient Safety (SEAPS) survey. AB - OBJECTIVE: To develop a survey to measure seniors' embracement of ambulatory patient safety self-advocacy behaviors, the Senior Empowerment and Advocacy in Patient Safety (SEAPS) survey. METHODS: Content was developed by review of published recommendations combined with interviews and focus groups with community members; items were generated for subscales based on the health belief model (HBM). Psychometric characteristics were assessed by cluster and correlation analyses on a pilot test of 143 community dwelling seniors; the ability of the subscales and demographic variables to predict reported behavior was investigated by multiple regression. RESULTS: The four subscales of the SEAPS were outcome efficacy (OE), attitudes (ATT), self-efficacy (SE) and behaviors (BEH). Cronbach alphas were 0.74 for ATT, 0.79 for BEH, and 0.91 for OE and SE. Analysis of variance showed that there were no differences in any subscale score by race, education level or frequency of doctor visits, but women were noted to have significantly higher scores (p<.01) on the ATT and SE subscales and for the total of all the scales. Multiple regressions showed that SE significantly predicted self-reported behavior (p<.001). OE was a significant predictor for whites (p<.001) but not for African-Americans (p=.24). CONCLUSIONS: We have developed a short, 21-item self-administered survey to assess seniors' views about their participation in safety tasks. PRACTICE IMPLICATIONS: We believe the SEAPS shows promise to be a tool for evaluating interventions and training programs aimed at improving seniors' self-advocacy skills. Effective interventions may improve the involvement of patients in their own safety in the clinical setting. PMID- 17851016 TI - Determinants and patient-reported long-term outcomes of physician empathy in oncology: a structural equation modelling approach. AB - OBJECTIVE: The aim of the present cross-sectional study was to explore patient- and physician-specific determinants of physician empathy (PE) and to analyse the influence of PE on patient-reported long-term outcomes in German cancer patients. METHODS: A postal survey was administered to 710 cancer patients, who had been inpatients at the University Hospital Cologne (response rate 49.5%). PE was measured with the German translation of the consultation and relational empathy (CARE) measure, and patient-reported long-term outcomes were assessed using the major (ICD-10) depression inventory (MDI) and the EORTC quality of life (Qol) questionnaire QLQ-C30. Hypotheses were tested by structural equation modelling. RESULTS: PE had (a) a moderate indirect effect on "depression" and a smaller indirect effect on "socio-emotional-cognitive Qol" by affecting "desire for more information from the physician regarding findings and treatment options" and (b) a moderate indirect effect on "socio-emotional-cognitive Qol" and a smaller effect on "depression" via "desire for more information about health promotion". The determinant with the greatest importance was "patient-perceived general busyness of hospital staff": it had a strong negative influence on PE, indirectly influencing "desire for more information from the physician regarding findings and treatment options" and also patients' "depression". CONCLUSION: PE seems to be an important pre-requisite for information giving by physicians and through this pathway having a preventive effect on depression and improving Qol. Conversely, physicians' stress negatively influences these relationships. PRACTICE IMPLICATIONS: The research findings suggest that reducing physicians' stress at the organizational and individual may be required to enhance patient physician communication. Empathy, as an outcome-relevant professional competence needs to be assessed and developed more intensively in medical students and physicians. PMID- 17851017 TI - The desmopressin stimulation test in dogs with Cushing's syndrome. AB - Desmopressin is a synthetic analogue of the hypothalamic peptide vasopressin and binds to specific pituitary vasopressin (V3) receptors. The V3-receptor is overexpressed in pituitary corticotrope tumors and the injection of desmopressin induces a marked ACTH and cortisol release in human patients with pituitary- (PDH), but not adrenal tumor (AT) dependent hyperadrenocorticism. In this prospective study, we investigated the effects of desmopressin on serum cortisol levels in 80 dogs suspected of Cushing's syndrome. The aim was to find a sensitive and specific test to exclude AT. According to standard tests the dogs were divided into 3 groups (group 1=other disease, n=27; group 2=PDH, n=46; group 3=AT, n=7). Desmopressin was injected as an i.v. bolus of 4microg and serial blood samples were collected before and after 30, 60 and 90min. Desmopressin significantly stimulated cortisol release in dogs with PDH (median 51%, range -24 to 563%; p<0.0001), whereas no increase was seen in dogs with AT (median -12%, range -44 to 5%; p=0.063) and in controls (median +7%, range -36 to 196%; p=0.131). Using a cut off value of 10% increase over baseline, it was possible to exclude AT in 75% of patients. The results of this study suggest that the desmopressin test could be a useful tool in differentiating pituitary from adrenal dependent Cushing's syndromes. Additional dogs with adrenocortical tumor must be tested in order to recommend its use in clinical practice. PMID- 17851018 TI - Expression of cytochrome P450 aromatase transcripts in buffalo (Bubalus bubalis) ejaculated spermatozoa and its relationship with sperm motility. AB - The cytochrome P450 aromatase (aromP450) deficient mice are infertile due to an impairment of spermatogenesis associated with a decrease in sperm motility and inability to fertilize oocytes. The sperm analysis showed decreased sperm motility in humans, having Cyp19 gene mutations. Further, in human, it was hypothesized that aromatase could be used as marker of sperm quality, particularly in the acquisition of its motility. However, there is no information regarding the expression of aromP450 in spermatozoa of farm animals including cattle and buffalo. In the present study, the expression of aromP450 in ejaculated buffalo spermatozoa and its relationship with sperm motility of ejaculated spermatozoa was studied by RT-PCR using total RNA isolated from buffalo-ejaculated spermatozoa. The results showed that conventional RT-PCR could not amplify aromatase transcript, while a nested PCR detected the presence of P450arom mRNA in buffalo-ejaculated spermatozoa. RT reaction followed by nested PCR was performed to compare the expression of aromatase transcripts in buffalo ejaculated spermatozoa of two category semen graded on the basis of mass motility and motile and non-motile spermatozoa separated by swim-up. A higher (P<0.01) expression of aromP450 transcript was found in spermatozoa obtained from the good quality semen (higher mass motility) to that in spermatozoa of poor quality semen (low mass motility). Similarly, higher (P<0.01) expression of aromP450 mRNA was observed in the motile spermatozoa as compared to non-motile spermatozoa separated from good quality semen by swim-up. It is concluded that the present study demonstrates a positive relation between aromatase transcript and mass motility of buffalo-ejaculated spermatozoa, which could be a putative marker for the quality of semen in farm animals, particularly the acquisition of sperm motility. PMID- 17851019 TI - The value of sentinel lymph node biopsy in ductal carcinoma in situ (DCIS) and DCIS with microinvasion of the breast. AB - AIM: Ductal carcinoma in situ (DCIS) refers to the preinvasive stage of breast carcinoma and should not give axillary metastases. Its diagnosis, however, is subject to sampling errors. The role of sentinel lymph node biopsy (SLNB) in management of DCIS or DCISM (with microinvasion) remains unclear. The purpose of this study was to review our experience with SLNB in DCIS and DCISM. METHODS: A review of 51 patients with a diagnosis of DCIS (n=45) or DCISM (n=6), who underwent SLNB and a definitive breast operation between January 1999 and December 2006, was performed. RESULTS: In 10 patients (19.6%) definitive histology revealed an invasive carcinoma. SLN (micro)metastases were detected in 5 out of 51 patients, of whom 2 had a preoperative diagnosis of grade III DCIS and 3 of DCISM. Three patients (75%) had micrometastases (< 2 mm) only. In 2 patients, histopathology demonstrated a macrometastasis (> 2 mm). All 5 patients underwent axillary dissection. No additional positive axillary lymph nodes were found. CONCLUSIONS: In case of a preoperative diagnosis of grade III DCIS or a grade II DCIS with comedo necrosis and DCIS with microinvasion, an SLNB procedure has to be considered because in almost 20% of the patients an invasive carcinoma is found after surgery. In this case the SLNB procedure becomes less reliable after a lumpectomy or ablation has been performed. SLN (micro)metastases were detected in nearly 10% of the patients. The prognostic significance of individual tumour cells remains unclear. PMID- 17851020 TI - Percutaneous radiofrequency ablation for the treatment of hepatocellular carcinoma in the caudate lobe. AB - AIMS: This study aimed to evaluate the efficacy and safety of percutaneous radiofrequency ablation (PRFA) for hepatocellular carcinoma (HCC) in the caudate lobe. PATIENTS AND METHODS: Between January 2001 and December 2006, 17 patients (twelve males and five females) who were between 33 and 68years old (mean 54.3), with caudate lobe HCC [2.0-6.5cm in diameter (mean 3.1)] were treated with either PRFA alone (n=14), or PRFA with percutaneous ethanol injection (n=3) under ultrasound guidance. The right or the anterior approach was used in 12 and 5 patients, respectively. RESULTS: All procedures were performed successfully. There was no mortality and major morbidity due to PRFA. Fourteen tumors (82%) were completely ablated after one to two sessions of treatment. During follow-up (range 3-60, mean 29.1months), two (14%) developed local recurrence. Intrahepatic metastases developed in 9 of 17 patients (53%). No distant metastasis was found. Four patients died (24%), 3 from tumor progression and 1 from hepatic failure. The 1-, 2-, and 4-year overall survivals were 88%, 80%, and 72%, respectively, and the progress free survivals were 47%, 20%, and 10%, respectively. CONCLUSIONS: PRFA is efficacious and safe for patients with HCC in the caudate lobe. PMID- 17851021 TI - [About high-doses of mannitol]. PMID- 17851022 TI - [Needle exsufflation could be the first line treatment of complete primary spontaneous pneumothorax at emergency room]. AB - Primary spontaneous pneumothorax (PSP) is associated with a low attributable morbidity-mortality because of absence of acute respiratory consequences in young and health subjects with normal baseline respiratory functions. In opposite, intercostal tube drainages, first-line surgical drainage or chemical pleurodesis are associated around 5% of complications or adverse effects. Guidelines were controversial, primary exsufflation becomes recommended, from now on. We report a case of a complete PSP coursed from four days in a current smoker patient. Needle exsufflation was first and once performed with mural suction associated with high oxygen treatment allowed denitrogenation. Pneumothorax was resolved. Re-expansion oedema and subcutaneous emphysema occurred consecutively aspiration, immediately. Simple and favourable outcome occurred, secondarily. Because of simplicity, safety, immediate efficacy and its reproducibility, needle aspiration could be first purposed in complete PSP in absence of haemodynamic or gasometrical consequences even if several days delay is present. PMID- 17851023 TI - [Secondary ischaemic lesions: how to prevent?]. AB - In addition to the initial lesions related to the brain injury, the final outcome depends also largely on the secondary ischaemic lesions. These lesions result from hypoperfusion whatever the mechanisms. It is then essential to detect early the conditions at risk of ischaemia, to be treated aggressively since the initial care. The multimodal monitoring is the only way to diagnose these conditions, to provide information about the mechanisms, and then to better adapt the treatment. Such an early detection helps to limit the consequences of the initial trauma, and may improve outcome. PMID- 17851024 TI - [Transfusion-related acute lung injury. A case report]. AB - A transfusion-related acute lung injury (Trali) is a noncardiogenic lung oedema occurring within six hours following the infusion of a blood component. It is a under-recognized transfusional accident, for which the aetiology and physiopathology are still controversial, evoking immunological or nonimmunological mechanisms which do not seem sufficient per se to cause this accident. A predisposing condition, associated with leucostasis in pulmonary vessels, is required. The pulmonary lesion is due to the activation of neutrophils in contact with endothelial cells of lung micro-capillary vessels. We report a case of Trali following the transfusion of the first red blood cells unit to a 26-year-old young woman. PMID- 17851025 TI - [About high-doses of mannitol]. PMID- 17851027 TI - 5-Aza-2'-deoxycytidine increases the expression of anti-angiogenic vascular endothelial growth factor 189b variant in human lung microvascular endothelial cells. AB - Vascular endothelial growth factor (VEGF) is involved in angiogenesis, growth, and tumour cell metastasis. VEGF is expressed as alternative splice variants, which exhibit angiogenic and anti-angiogenic properties. We determined the effect of 5-Aza-2'-deoxycytidine (5-dAzaC) DNA methyltransferase (DNMTs) inhibitor on angiogenic and anti-angiogenic VEGF variants expression in immortalized human lung microvascular endothelial cells (HLMEC). Employing reverse transcription, real-time quantitative PCR (RQ-PCR), and Western blot analysis, we determined that 5-dAzaC decreased VEGF(121a) and VEGF(165a) angiogenic, and VEGF(121b) and VEGF(165b) anti-angiogenic variants expression in HLMEC. However, this DNMTs inhibitor significantly increases expression of VEGF(189b) anti-angiogenic variant transcript and protein in HLMEC. Our results suggest that the DNMTs activity may have an influence on the expression of angiogenic and anti angiogenic VEGF variants in human lung microvascular endothelial cells. PMID- 17851026 TI - Cholesterol levels in HIV-HCV infected patients treated with lopinavir/r: results from the SCOLTA project. AB - BACKGROUND: It is not known whether antiretroviral therapy (ART) including lopinavir/r has a different effect on the lipid metabolism in HIV patients co infected with HCV. This study investigated changes in lipid levels, comparing patients with HIV infection alone and those with HCV too, in the lopinavir/r cohort of the SCOLTA project. METHODS: We analyzed the data for the lopinavir/r nationwide cohort from 25 Italian infectious disease departments, which comprises 743 HIV-infected patients followed prospectively, comparing subjects with HIV-HCV co-infection and those with single-infection. RESULTS: At enrolment, co-infected patients had significantly lower mean cholesterol than HCV negative cases (162+/ 43mg/dL vs. 185+/-52mg/dL, p=0.0009). Total and non-HDL cholesterol and triglycerides rose significantly from baseline in HIV single-infection patients, but not in those with co-infection. The patients with dual HIV-HCV infection, treated with an ART regimen including lopinavir/r, have only limited increases in total and non-HDL cholesterol and triglycerides. CONCLUSIONS: Changes in serum lipids in co-infected patients differed significantly from those in patients without HCV. It remains to be seen whether this is associated with a lower risk of progression of atherosclerotic disease. PMID- 17851028 TI - [Is surgery required for patients with isolated adrenal metastasis of non-small cell lung carcinoma?]. AB - BACKGROUND: No consensus yet governs management of solitary adrenal metastasis of non-small cell lung cancer (NSCLC). Although classically considered incurable, various case reports and small series indicate that surgical treatment may improve long-term survival. The aim of this study was to review our experience and to identify factors that may affect survival. METHODS: From January 1989 through June 2006, 26 patients (21 men and 5 women; mean age: 54+/-10 years) underwent complete resection of an isolated adrenal metastasis after surgical treatment of NSCLC. The adrenal metastasis was diagnosed at the same time as the NSCLC in 6 patients and subsequently in 20 patients. Median disease-free interval for patients with metachronous metastasis was 13.8 months (range: 4.5 to 60.1 months). RESULTS: The overall 5- and 10-year survival rates were 31 and 21% respectively. Univariate and multivariate analysis showed that a disease-free interval longer than 6 months was a significant independent predictor of longer survival in patients after adrenalectomy. All patients with a disease-free interval of less than 6 months died within 2 years of surgery. After resection of an isolated adrenal metastasis diagnosed more than 6 months after lung resection, the 5-year survival rate was 49%. Adjuvant therapy and pathological staging of NSCLC did not affect survival. CONCLUSION: Surgical resection of subsequent isolated adrenal metastasis with a disease-free interval longer than 6 months can lead to long-term survival in patients with previous complete resection of the primary NSCLC. PMID- 17851029 TI - Poly-N-acetylglucosamine mediates biofilm formation and detergent resistance in Aggregatibacter actinomycetemcomitans. AB - Clinical isolates of the periodontopathogen Aggregatibacter actinomycetemcomitans form matrix-encased biofilms on abiotic surfaces in vitro. A major component of the A. actinomycetemcomitans biofilm matrix is poly-beta-1,6-N-acetyl-d glucosamine (PGA), a hexosamine-containing polysaccharide that mediates intercellular adhesion. In this report, we describe studies on the purification, structure, genetics and function of A. actinomycetemcomitans PGA. We found that PGA was very tightly attached to A. actinomycetemcomitans biofilm cells and could be efficiently separated from the cells only by phenol extraction. A. actinomycetemcomitans PGA copurified with LPS on a gel filtration column. (1)H NMR spectra of purified A. actinomycetemcomitans PGA were consistent with a structure containing a linear chain of N-acetyl-d-glucosamine residues in beta(1,6) linkage. Genetic analyses indicated that all four genes of the pgaABCD locus were required for PGA production in A. actinomycetemcomitans. PGA mutant strains still formed biofilms in vitro. Unlike wild-type biofilms, however, PGA mutant biofilms were sensitive to detachment by DNase I and proteinase K. Treatment of A. actinomycetemcomitans biofilms with the PGA-hydrolyzing enzyme dispersin B made them 3 log units more sensitive to killing by the cationic detergent cetylpyridinium chloride. Our findings suggest that PGA, extracellular DNA and proteinaceous adhesins all contribute to the structural integrity of the A. actinomycetemcomitans biofilm matrix. PMID- 17851030 TI - Role of Toll-like receptor 2 in innate resistance to Group B Streptococcus. AB - The Gram-positive bacterium Group B Streptococcus (GBS) is an important cause of serious neonatal and adult infections. Toll-like receptor 2 (TLR2) recognizes components of the cell wall of Gram-positive bacteria and is critical for defense against certain invasive pathogens. In GBS, penicillin-binding protein 1a (PBP1a), encoded by ponA, is required for virulence. PBPs participate in cell wall synthesis and in previous studies; the absence of PBP1a was shown to result in subtle changes in the cell wall ultrastructure. Here, we examine the role of TLR2 in defense against GBS infection and the impact of mutation of ponA on TLR2 mediated host responses. We demonstrate TLR2-recognition of both wild-type (WT) GBS and the ponA mutant in vitro. TLR2(-/-) mice were significantly more susceptible than WT mice to infection with either strain of GBS, indicating a crucial role for TLR2 in defense against GBS. Additionally, the ponA mutant was severely attenuated for virulence in both strains of mice. The mutation in ponA did not affect cytokine expression by WT or TLR2(-/-) mice. These data indicate that TLR2 is required for host defense against GBS and this response is unaffected by the absence of PBP1a and the resultant changes in cell wall ultrastructure. PMID- 17851031 TI - Relationship of the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) to functional, emotional, and neuropsychological outcomes. AB - OBJECTIVE: To explore the relationship of the Multiple Sclerosis Neuropsychology Questionnaire (MSNQ; [Benedict, R. H. B., Cox, D., Thompson, L. L., Foley, F., Weinstock-Guttman, B., & Munschauer, F. (2004). Reliable screening for neuropsychological impairment in multiple sclerosis. Multiple Sclerosis, 10, 675 678; Benedict, R. H. B., Munschauer, F., Linn, R., Miller, C., Murphy, E., Foley, F., et al. (2003). Screening for multiple sclerosis cognitive impairment using a self-administered 15-item questionnaire. Multiple Sclerosis, 9, 95-101]), a self report screening measure of neuropsychological functioning in multiple sclerosis (MS), with everyday life functioning, neuropsychological functioning, and mood in MS. Additionally, to investigate the validity, sensitivity, and specificity of the MSNQ to predict cognitive impairment in persons with MS. STUDY DESIGN: Cross sectional, correlational analyses; analyses of sensitivity and specificity. SETTING: Neuropsychology lab-based study with adults from the community including persons with MS (n=48) and healthy adults (n=40). MAIN OUTCOME MEASURES: Subjective and objective measures of everyday life functioning, neuropsychological functioning, and mood; ROC curve of MSNQ-Self report and MSNQ Informant report, sensitivity and specificity of MSNQ-S and MSNQ-I. RESULTS: Correlational analyses indicate the MSNQ-S is significantly correlated with mood and self-reports of functioning, but not with objectively measures daily functioning and to only few neuropsychological tests. The MSNQ-I was not significantly correlated to mood, self-report of daily functioning or objectively measured daily functioning, but was significantly correlated with several measures of neuropsychological functioning. CONCLUSION: The MSNQ-S was not supported as a sensitive screen for neuropsychological impairment in MS. However, the MSNQ-I was supported as a valid and sensitive screen of cognitive impairment in persons with MS, although further research is needed to determine an optimal cutoff score for this measure. PMID- 17851032 TI - Visual and cognitive predictors of driving safety in Parkinson's disease patients. AB - This study assessed the clinical utility of contrast sensitivity (CS) relative to attention, executive function, and visuospatial abilities for predicting driving safety in participants with Parkinson's disease (PD). Twenty-five, non-demented PD patients completed measures of contrast sensitivity, visuospatial skills, executive functions, and attention. All PD participants also underwent a formal on-road driving evaluation. Of the 25 participants, 11 received a marginal or unsafe rating on the road test. Poorer driving performance was associated with worse performance on measures of CS, visuospatial constructions, set shifting, and attention. While impaired driving was associated with a range of cognitive and visual abilities, only a composite measure of executive functioning and visuospatial abilities, and not CS or attentional skills, predicted driving performance. These findings suggest that neuropsychological tests, which are multifactorial in nature and require visual perception and visual spatial judgments are the most useful screening measures for hazardous driving in PD patients. PMID- 17851033 TI - An examination of the fear of bodily sensations and body hypervigilance as predictors of emotion regulation difficulties among individuals with a recent history of uncued panic attacks. AB - Recent studies have demonstrated that individuals with a history of uncued panic attacks exhibit heightened difficulties in emotion regulation, including experiential avoidance, emotional non-acceptance, and lack of emotional clarity. The purpose of this study was to extend these findings by examining whether the fear of bodily sensations predicted the presence of experiential avoidance and emotional non-acceptance and whether body hypervigilance predicted a lack of emotional clarity in a sample of 91 individuals with a recent history (past year) of uncued panic attacks. Findings indicated that the fear of bodily sensations predicts experiential avoidance, emotional non-acceptance, and lack of emotional clarity above and beyond other panic-relevant variables. No evidence was found for a relationship between body hypervigilance and any emotion regulation difficulty. Findings are discussed in terms of their implications for improving the understanding of the development and treatment of emotion regulation difficulties among individuals with a history of panic attacks. PMID- 17851034 TI - The relationship between psychiatric symptomatology and motivation of challenging behaviour: a preliminary study. AB - In addition to explaining challenging behaviour by way of behaviour analytic, functional analyses, challenging behaviour is increasingly explained by way of psychiatric symptomatology. According to some researchers, the two approaches complement each other, as psychiatric symptomatology may form a motivational basis for the individual's response to more immediate environmental challenges, like deprivation and aversive conditions. The most common example may be that depressive mood may render task demands aversive. Consequently, the person may show escape-motivated challenging behaviour in the presence of demands. The question becomes whether, or to what extent, relationships between psychiatric symptomatologies and particular functions of challenging behaviour exist. In the present, preliminary study, PAS-ADD checklist, a psychiatric screening instrument, and motivation assessment scale (MAS) were employed in order to investigate this issue. The results show that symptomatologies are largely unrelated to particular behavioural functions. Practical implications are discussed. PMID- 17851035 TI - GFAM: evolving Fuzzy ARTMAP neural networks. AB - This paper focuses on the evolution of Fuzzy ARTMAP neural network classifiers, using genetic algorithms, with the objective of improving generalization performance (classification accuracy of the ART network on unseen test data) and alleviating the ART category proliferation problem (the problem of creating more than necessary ART network categories to solve a classification problem). We refer to the resulting architecture as GFAM. We demonstrate through extensive experimentation that GFAM exhibits good generalization and is of small size (creates few ART categories), while consuming reasonable computational effort. In a number of classification problems, GFAM produces the optimal classifier. Furthermore, we compare the performance of GFAM with other competitive ARTMAP classifiers that have appeared in the literature and addressed the category proliferation problem in ART. We illustrate that GFAM produces improved results over these architectures, as well as other competitive classifiers. PMID- 17851036 TI - Modeling and simulation of intravenous levetiracetam pharmacokinetic profiles in children to evaluate dose adaptation rules. AB - PURPOSE: To develop a pharmacokinetic model for intravenous levetiracetam in children, based on adult intravenous data and pediatric oral data. METHODS: Data from two adult Phase-I studies in which levetiracetam was given intravenously were utilized to develop the adult population pharmacokinetic two-compartment intravenous model. After model qualification, combination with an existing pediatric one-compartment oral population pharmacokinetic model enabled simulation of twice-daily intravenous infusions of levetiracetam in children. Median and 90% confidence intervals for C(trough), C(max) (end of infusion) and AUC(tau) were simulated for 2000 children and compared to the values observed in adults. RESULTS: The population pharmacokinetic two-compartment model successfully described intravenous levetiracetam pharmacokinetics in healthy adults. After combination with the oral pediatric population model, steady-state concentrations at the end of 15-, 30- and 60 min b.i.d. levetiracetam intravenous infusions in children were predicted to be 29-41, 17-24 and 6-13% higher than those observed after oral dosing of 30 mg/kg b.i.d. Concentrations returned to the range of oral exposures within 1h after the infusion peak. The combined model predicted that steady-state peak plasma concentrations and AUC(tau) in children receiving 30 mg/kg twice daily as 15 min intravenous infusions were within the range of predicted and observed C(max,ss) and AUC(tau )values of adults receiving 15 min intravenous infusions of 1500 mg levetiracetam. CONCLUSIONS: The simulations suggest that levetiracetam may be administered intravenously in children as 15 min infusions. PMID- 17851037 TI - Intersubject variability in the anterior extent of the optic radiation assessed by tractography. AB - INTRODUCTION: Temporal lobe resection for epilepsy involves a risk of damaging the anterior part of the optic radiation, Meyer's loop, causing a contralateral upper quadrant visual field defect. This study aims to assess the intersubject variability in the course of Meyer's loop in vivo by diffusion tensor imaging and tractography. METHODS: Seven healthy volunteers and two patients with previous temporal lobe resection were recruited. Diffusion tensor imaging and tractography were used to visualize the optic radiation. The distances from the anterior edge of Meyer's loop to landmarks in the temporal lobe were calculated. RESULTS: In the healthy subjects, the mean distance between the most anterior part of Meyer's loop and the temporal pole was 44 mm (range 34-51 mm). Meyer's loop did not reach the tip of the temporal horn in any subject. A disruption in Meyer's loop could be demonstrated in the patient with quadrantanopia after temporal lobe resection. CONCLUSIONS: Meyer's loop has a considerable variability in its anterior extent. Tractography may be a useful method to visualize Meyer's loop, and assess the risk of a visual field defect, prior to temporal lobe resection. PMID- 17851038 TI - Usefulness of a morning routine EEG recording in patients with juvenile myoclonic epilepsy. AB - OBJECTIVE: To evaluate if a standard awake EEG recording in the morning is superior to afternoon awake EEG session in detecting generalized epileptiform discharges (GEDs) in patients with juvenile myoclonic epilepsy (JME). METHODS: The study group included 29 consecutive patients (23 women; mean age 22.3+/-6.3 years; age at onset of JME 15.4+/-3.4 years) with JME. Out of 29 patients 5 were untreated, 9 patients were treated with valproate, 8 with lamotrigine, 6 with levetiracetam and 1 patient with valproate plus phenobarbital. Two routine consecutive interictal EEG recordings were performed at 9a.m. and at 3p.m., respectively, while the subject was awake, on the same day after a a regular nocturnal sleep at own home. RESULTS: The morning EEG recording showed GEDs (i.e., generalized polispike and waves, photoparoxysmal response, or both). in 20/29 patients. In 15 of these 20 patients, the afternoon recording was normal and this difference was statistically significant (p < or = 0.001). Moreover, there was a striking reduction of GEDs in three of the remaining five patients. Nine/29 patients had both morning and afternoon EEG recording normal. CONCLUSIONS: The results of this study have illustrated a significant greater rate of detection of generalized epileptiform abnormalities by performing standard awake EEG in the morning in comparison with an afternoon session. PMID- 17851039 TI - Commentary on the effects of a ketogenic diet enriched with omega-3 polyunsaturated fatty acids on plasma phospholipid fatty acid profile in children with drug-resistant epilepsy. PMID- 17851040 TI - Lamotrigine-associated exacerbation of positive symptoms in paranoid schizophrenia. PMID- 17851041 TI - Association between PNPO and schizophrenia in the Japanese population. AB - Accumulating evidence suggests that both homocysteine metabolism and monoaminergic neurotransmitter systems are important in schizophrenia pathology. We hypothesized that the gene PNPO (pyridoxine 5'-phosphatase oxidase gene) might be a candidate for susceptibility to schizophrenia because PNPO encodes pyridoxamine 5'-phosphate oxidase (EC 1.4.3.5), a rate-limiting enzyme in pyridoxal 5'-phosphate (PLP, vitamin B(6)) synthesis. PLP is a metabolically active form of vitamin B(6) and thus, is required as a co-factor for enzymes involved in both homocysteine metabolism and synthesis of neurotransmitters such as catecholamine. We examined 8 single nucleotide polymorphisms (SNPs) in PNPO and its 5'-flanking regions in 359 schizophrenia patients and 582 control subjects. Four marker regions of PNPO showed significant levels of allelic associations with schizophrenia (the highest was rs2325751, P=0.004). In addition, the haplotype case-control study revealed a significant association (permutation P<0.00001) between PNPO and schizophrenia. These findings suggest that variations in PNPO may contribute to overall genetic risk for schizophrenia in the Japanese population. PMID- 17851042 TI - Association of symptomatology and cognitive deficits to functional capacity in schizophrenia. AB - PURPOSE: This study aimed to evaluate the association of positive and negative symptoms, as well as of neurocognition to functional status in patients with schizophrenia. Participants were 309 veterans with DSM-IV-diagnosed schizophrenia or schizoaffective disorder who were enrolled in a 12-month double-blind clinical trial and randomized to receive either 5 to 20 mg/d of oral olanzapine or haloperidol. Patients were assessed at study entry and at 3, 6 and 12-months on the PANSS and measures of verbal memory, verbal fluency, fine motor coordination, visual sequencing/set shifting, and conceptual reasoning. Functional status was evaluated by the Heinrichs-Carpenter Quality of Life Scale (QLS) and by days of employment in the past 30. Hierarchical regression models examined the association of functional status with symptomatology and three neurocognitive factors (motor skills, memory and card sorting), controlling for demographics and visit number. A mixed effects model was used to adjust for repeated observations from the same subjects. RESULTS: The PANSS explained 16% additional variance in QLS total score after accounting for demographics and visit number (p<.001), while the neurocognitive factors explained only 4% additional variance beyond the effect of symptoms. When neurocognition was entered before symptoms, it explained an additional 8% of the variance on the QLS total score, while the PANSS explained an additional 12% over and above neurocognition. CONCLUSIONS: These findings suggest that symptoms may pose an equal or greater impediment to functional capacity independent of neurocognition, at least in younger non institutionalized people with schizophrenia. PMID- 17851043 TI - Predictors of the evolution towards schizophrenia or mood disorder in patients with schizophreniform disorder. AB - In this study, 56 patients affected by schizophreniform disorder (SFD), as their first lifetime mental disorder, were re-evaluated 7.9+/-4.7 yrs (2-17 yrs) after their first hospitalization. At follow-up, schizophrenia (SC) was diagnosed in 25 patients (46%), a mood disorder (MD) in 19 (35%), a non-SC psychotic disorder in 10 (18%) and no disorder in 2 (4%). The evolution towards SC was predicted by the presence of blunted affect (OR: 1.88) and by poor pre-morbid functioning (OR: 1.10) at the index hospitalization. Our data suggest that SFD may represent the first psychotic presentation of different disorders and the evolution towards SC or a MD seems to be influenced by the pre-morbid level of functioning and by the presence of blunted affect. PMID- 17851044 TI - Schizophrenia and the inferior parietal lobule. AB - OBJECTIVE: Studies of the neuroanatomical localization of schizophrenia have not given sufficient attention to the inferior parietal lobule (IPL). METHODS: A search of the medical literature was carried out for links between schizophrenia and the IPL. RESULTS: Structural differences in the IPL in schizophrenia were reported by 10 recent neuroimaging studies, although the studies did not all agree with each other. Functional differences in the IPL in schizophrenia have been prominently reported in four areas: sensory integration, body image, concept of self, and executive function. CONCLUSION: The IPL appears to be an important, but relatively neglected, component of the frontal-limbic-temporal-parietal neural network involved in the schizophrenia disease process. To encourage histopathological research of this area, the Stanley Medical Research Institute is making available a new collection of sucrose-fixed IPL tissue from 25 individuals with schizophrenia and 25 matched controls. Additional imaging and functional studies are needed to better define the network and role of the IPL. PMID- 17851046 TI - Human umbilical cord epithelial cells express Notch1: implications for its epidermal-like differentiation. AB - BACKGROUND: Notch1 receptor, a member of the Notch signaling pathway, is involved in the terminal differentiation process of epidermal keratinocytes. Human umbilical cord epithelia are continuous with embryonic and fetal epidermis during development, display cellular stratification and express differentiation markers related to the epidermis. As such, we hypothesized that Notch1 may be present in human umbilical cord epithelial cells (HUCEC). OBJECTIVE: To investigate the expression of Notch1 in HUCEC in vivo and in vitro. METHODS: Umbilical cord sections were probed with antibodies specific for Notch1, -2, -3, and -4. Expression of Notch transcripts in HUCEC in vitro was examined by RT-PCR analysis and protein expression was identified using immunocytochemistry and western blotting analysis. Using a three-dimensional organotypic culture system that promotes epidermal terminal differentiation, Notch1 expression was examined and changes in expression level were analysed using real-time quantitative PCR. RESULTS: Immunostaining of cord epithelia revealed expression of all four Notch receptors, with differential spatial distribution. Notch mRNA and protein were expressed in HUCEC in vitro. Specifically, western blotting revealed the presence of the transmembrane unit of the mature Notch1 heterodimeric receptor in HUCEC and epidermal keratinocytes. In organotypic culture, Notch1 mRNA was expressed in HUCEC with protein localised to the upper epithelial layers. Interestingly, Notch1 gene expression was down-regulated in HUCEC in organotypic culture compared to cells in submerged monolayer culture. CONCLUSION: HUCEC express Notch1 as in epidermal keratinocytes. The presence of Notch1 has implications for its involvement in the differentiation program of cord epithelia as a stratified epithelial tissue. PMID- 17851045 TI - Neuromagnetic evidence of broader auditory cortical tuning in schizophrenia. AB - Deficits in basic auditory perception have been described in schizophrenia. Previous electrophysiological imaging research has documented a structure function disassociation in the auditory system and altered tonotopic mapping in schizophrenia. The present study examined auditory cortical tuning in patients with schizophrenia. Eighteen patients with schizophrenia and 15 comparison subjects were recorded in a magnetoencephalographic (MEG) experiment of auditory tuning. Auditory cortical tuning at 1 kHz was examined by delivering 1 kHz pure tones in conjunction with pure tones at 5 frequencies surrounding and including 1 kHz. Source reconstruction data were examined for evidence of frequency specificity for the M100 component. There was a significant broadening of tuning in the schizophrenia group evident for the source amplitude of the M100. The frequently reported reduction in anterior-posterior source asymmetry for individuals with schizophrenia was replicated in this experiment. No relationships between symptom severity ratings and MEG measures were observed. This finding suggests that the frequency specificity of the M100 auditory evoked field is disturbed in schizophrenia, and may help explain the relatively poor behavioral performance of schizophrenia patients on simple frequency discrimination tasks. PMID- 17851047 TI - In vitro activity of essential oil of Myrtus communis L. against Helicobacter pylori. PMID- 17851048 TI - High prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae in Nepal. PMID- 17851049 TI - Urinary Tract Infections Supplement: International Symposia on Urinary Tract Infection, Weimar and Munich, Germany. Preface. PMID- 17851050 TI - Comparative activities of colistin, rifampicin, imipenem and sulbactam/ampicillin alone or in combination against epidemic multidrug-resistant Acinetobacter baumannii isolates producing OXA-58 carbapenemases. AB - This study evaluated the activity of colistin, rifampicin, imipenem and sulbactam/ampicillin alone or in combination against nine epidemic multidrug resistant Acinetobacter baumannii isolates producing OXA-58 carbapenemase in Naples, Italy. The isolates were susceptible to colistin but differed in their resistance to imipenem and rifampicin. Time-kill studies showed a bactericidal effect for colistin but not for imipenem, rifampicin or sulbactam/ampicillin used as single agents. Synergism was observed with combinations of rifampicin+imipenem or sulbactam/ampicillin for all isolates and with colistin+rifampicin for isolates showing higher minimum inhibitory concentrations for rifampicin. Combined use of the antimicrobials tested may provide good therapeutic options for OXA-58 carbapenemase-producing A. baumannii infections. PMID- 17851051 TI - Development of an aciclovir implant for the effective long-term control of herpes simplex virus type-1 infection in Vero cells and in experimentally infected SKH-1 mice. AB - Human herpes simplex virus type-1 (HSV-1) is treatable with oral doses of an antiviral agent such as aciclovir (ACV), a drug that has poor bioavailability. An alternative for delivering ACV would employ a long-lived subcutaneous implant that would allow for near zero-order drug delivery kinetics. This study aimed to develop an implant composed of a matrix of silicone and ACV that is capable of sustained long-term release of ACV. Once the implants had been created, release of ACV from the implants was determined and quantified in vitro using a spectrophotometric assay for the drug. Solvent-exposed surface area of the implant (2.86 mm(2), 6.28 mm(2), 34.62 mm(2) and 100.48 mm(2)) had a significant effect on release kinetics, whereas temperature (37 degrees C, 25 degrees C and 4 degrees C) and pH (6.0, 7.0 and 8.0) did not. The implants were also used successfully to suppress HSV-1 (KOS)-induced cytopathic effect in cultured Vero cells. The implants protected HSV-1-infected SKH-1 mice from viral reactivation (n = 37; P = 0.0367) via ultraviolet light compared with mice that were untreated (n = 37). Furthermore, mice that received silicone-only implants had no lowered risk of reactivation (n = 34; P = 0.7268), demonstrating the antiviral efficacy of the ACV implants. PMID- 17851052 TI - Exposure to quinolones is associated with carbapenem resistance among colistin susceptible Acinetobacter baumannii blood isolates. AB - In this study, we explored risk factors associated with bacteraemia caused by colistin-susceptible/carbapenem-resistant (Co(S)/Ca(R)) Acinetobacter baumannii. A retrospective cohort study of hospitalised patients with A. baumannii bacteraemia was performed at a tertiary care hospital over a 44-month period. Thirty-nine patients with bacteraemia due to A. baumannii (35 Intensive Care Unit and 4 ward patients) were included in the analysis. Twenty-five patients (64%) had bacteraemia due to Co(S)/Ca(R)A. baumannii and 14 patients (36%) had bacteraemia due to colistin-susceptible/carbapenem-susceptible A. baumannii. Mortality was 56% (14/25) and 35.7% (5/14) for patients in the two groups, respectively (P=0.22). Bivariate analysis showed that prior exposure to fluoroquinolones (P=0.01) and antipseudomonal penicillins (P=0.004) as well as a higher number of antibiotics in use on the day of bacteraemia (P=0.02) were associated with isolation of a Co(S)/Ca(R) strain among patients with A. baumannii bacteraemia. Multivariate analysis using a backward logistic regression model showed that only exposure to fluoroquinolones was associated with development of Co(S)/Ca(R)A. baumannii bacteraemia (odds ratio=11.6; 95% confidence interval 2.4-55.9; P=0.02). The appearance of Co(S)/Ca(R)A. baumannii infections represents a major threat to critically ill hospitalised patients. Exposure to fluoroquinolones is an independent risk factor for development of Co(S)/Ca(R)A. baumannii bacteraemia. PMID- 17851053 TI - Fabrication and in vitro drug release study of microsphere drug delivery systems based on amphiphilic poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide]-g-poly(L lactide) graft copolymers. AB - Biodegradable amphiphilic graft copolymers with different compositions were synthesized by grafting poly(L-lactide) (PLLA) sequences onto a water-soluble poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA) backbone. The critical micelle concentration (CMC) of the graft polymers was determined by fluorescence probe technique. Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide) assay, the graft polymers were proved to have low cytotoxicity. Based on the specific physicochemical property of the graft copolymers, submicron sized microsphere drug delivery systems were prepared by a very convenient "ultrasonic dispersion method", which did not involve toxic organic solvents. The drug-loaded microspheres had a regular spherical shape with a narrow size distribution. A hydrophobic drug, prednisone acetate, was encapsulated into polymeric microspheres and the in vitro drug release was studied. PMID- 17851054 TI - Evaluation of rule interestingness measures in medical knowledge discovery in databases. AB - OBJECTIVE: We discuss the usefulness of rule interestingness measures for medical KDD through experiments using clinical datasets, and, based on the outcomes of these experiments, also consider how to utilize these measures in postprocessing. METHODS AND MATERIALS: We first conducted an experiment to compare the evaluation results derived from a total of 40 various interestingness measures with those supplied by a medical expert for rules discovered in a clinical dataset on meningitis. We calculated and compared the performance of each interestingness measure to estimate a medical expert's interest using f-measure and correlation coefficient. We then conducted a similar experiment for hepatitis. RESULTS AND CONCLUSION: The comprehensive results of experiments on meningitis and hepatitis indicate that the interestingness measures, accuracy, chi-square measure for one quadrant, relative risk, uncovered negative, and peculiarity, have a stable, reasonable performance in estimating real human interest in the medical domain. The results also indicate that the performance of interestingness measures is influenced by the certainty of a hypothesis made by the medical expert, and that the combinational use of interestingness measures will contribute to support medical experts to generate and confirm their hypotheses through human-system interaction. PMID- 17851055 TI - A multiple kernel support vector machine scheme for feature selection and rule extraction from gene expression data of cancer tissue. AB - OBJECTIVE: Recently, gene expression profiling using microarray techniques has been shown as a promising tool to improve the diagnosis and treatment of cancer. Gene expression data contain high level of noise and the overwhelming number of genes relative to the number of available samples. It brings out a great challenge for machine learning and statistic techniques. Support vector machine (SVM) has been successfully used to classify gene expression data of cancer tissue. In the medical field, it is crucial to deliver the user a transparent decision process. How to explain the computed solutions and present the extracted knowledge becomes a main obstacle for SVM. MATERIAL AND METHODS: A multiple kernel support vector machine (MK-SVM) scheme, consisting of feature selection, rule extraction and prediction modeling is proposed to improve the explanation capacity of SVM. In this scheme, we show that the feature selection problem can be translated into an ordinary multiple parameters learning problem. And a shrinkage approach: 1-norm based linear programming is proposed to obtain the sparse parameters and the corresponding selected features. We propose a novel rule extraction approach using the information provided by the separating hyperplane and support vectors to improve the generalization capacity and comprehensibility of rules and reduce the computational complexity. RESULTS AND CONCLUSION: Two public gene expression datasets: leukemia dataset and colon tumor dataset are used to demonstrate the performance of this approach. Using the small number of selected genes, MK-SVM achieves encouraging classification accuracy: more than 90% for both two datasets. Moreover, very simple rules with linguist labels are extracted. The rule sets have high diagnostic power because of their good classification performance. PMID- 17851056 TI - p53AIP1 expression can be a prognostic marker in non-small cell lung cancer. AB - AIMS: p53AIP1 is a potential mediator of p53-dependent apoptosis that is mutated in many kinds of carcinoma. To investigate the role of this gene for non-small cell lung cancer, we compared the relationship between p53AIP1 gene expression and clinicopathological status of lung cancer. MATERIALS AND METHODS: Seventy samples from non-small cell lung cancer patients were obtained between 1997 and 2003. For quantitative evaluation of RNA expression by polymerase chain reaction (PCR) we used the Taqman PCR methods. Exons 5-8 of the p53 gene were analysed using PCR-single-stranded conformation polymorphism and sequenced for mutation analysis. RESULTS: p53AIP1 gene expression levels in the lymph node metastasis positive group were significantly lower than in the negative group (positive 35.1+/-83.9; negative 64.2+/-113.4; P=0.0486). The overall survival of the p53AIP1 low expression group was significantly worse than that of the p53AIP1 high expression group (P=0.0206). In the multivariate Cox proportional hazard model, p53AIP1 (P=0.0489) was the independent predictor for overall survival. When we investigated mutation analyses of the p53 gene, we could find several point mutations in 15.7% of all samples. However, there was no relationship between p53AIP1 expression and p53 status. CONCLUSIONS: These data suggest that the p53AIP1 gene is important for non-small cell lung cancer progression and may be a possible prognostic marker. PMID- 17851057 TI - Dexamethasone-loaded poly(epsilon-caprolactone) intravitreal implants: a pilot study. AB - PURPOSE: Poly(epsilon-caprolactone) (PCL) is a biodegradable and biocompatible polymer that presents a very low degradation rate, making it suitable for the development of long-term drug delivery systems. The objective of this pilot study is to evaluate the feasibility and characteristics of PCL devices in the prolonged and controlled intravitreous release of dexamethasone. METHODS: The in vitro release of dexamethasone was investigated and the implant degradation was monitored by the percent of mass loss and by changes in the surface morphology. Differential scanning calorimetry was used to evaluate stability and interaction of the implant and the drug. The short-term tolerance of the implants was studied after intravitreous implantation in rabbit eye. RESULTS: PCL implant allows for a controlled and prolonged delivery of dexamethasone since it releases 25% of the drug in 21 weeks. Its low degradation rate was confirmed by the mass loss and scanning electron microscopy studies. Preliminary observations show that PCL intravitreous implants are very well tolerated in the rabbit eye. CONCLUSION: This study demonstrates the PCL drug delivery systems allowed to a prolonged release of dexamethasone in vitro. The implants demonstrated a strikingly good intraocular short-term tolerance in rabbits eyes. The in vitro and preliminary in vivo studies tend to show that PCL implants could be of interest when long-term sustained intraocular delivery of corticosteroids is required. PMID- 17851059 TI - Weight loss and asthma control in severely obese asthmatic females. AB - BACKGROUND: Obesity is proposed to represent an important predisposing condition to serious respiratory disturbances including asthma. The effects of consistent weight loss on asthma control are not well known. We investigated the effect of weight reduction induced by bariatric surgery on asthma control in severely obese asthmatic patients. PATIENTS AND METHODS: A consecutive series of 12 asthmatic obese females who had laparoscopic adjustable gastric banding (OB group) and 10 non-operated asthmatic obese females as control group (CG). Body mass index (BMI), Asthma Control Test (ACT), pulmonary function test (PFT), exhaled nitric oxide (NO) were evaluated at baseline and after 1 year. RESULTS: Mean BMI (kg/m(2)) of OB group decreased from 45.2+/-4.7 before surgery to 34.8+/-4.2 post operatively. After surgery the overall ACT score in OB group significantly improved from 18.7 to 22.2 (p<0.001), while it remained unchanged in CG (from 18.8 to 18.6, p=0.73). In particular, in OB group the parameters of shortness of breath and rescue medication use were significantly improved respectively from 3.2 and 3.9 before surgery to 4.2 and 4.6 after surgery (always p<0.05). Accordingly, none of the CG who did not experience any weight loss was able to obtain a full asthma control. In the OB group after the surgery PFT significantly improved as compared to CG. No significant difference in exhaled NO was found both in OB group after surgery as compared to before surgery. CONCLUSION: Consistent weight loss in severely obese patients with asthma is associated to improvement in respiratory symptoms and lung function. However, the mechanisms underlying the effect of large body mass changes on asthma would require further studies. PMID- 17851060 TI - Anti-endothelial cell antibodies in patients with interstitial lung diseases. AB - BACKGROUND: Anti-endothelial cell antibodies (AECA) are circulating antibodies that bind to endothelial antigens and induce endothelial cell damage. AECA have been detected in patients with collagen vascular disease (CVD) and their presence is associated with interstitial lung disease (ILD) in cases of CVD. However, the prevalence of AECA in patients with idiopathic interstitial pneumonias (IIPs) is not known. METHODS: We investigated the prevalence of AECA in patients with IIPs. We also examined whether the expression of AECA differed among the histologic subgroups usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP), and compared the values with those of CVD-associated ILD (CVD ILD). Twenty patients with IIPs and 24 patients with CVD-ILD were studied. Serum samples were examined for AECA by cellular enzyme-linked immunosorbent assay (ELISA) using human umbilical vein endothelial cells. Values are expressed as ELISA ratios (ER). RESULTS: All sera from patients with idiopathic pulmonary fibrosis (IPF)/UIP were negative for AECA, whereas 5 out of 10 with idiopathic NSIP, 5 out of 14 with CVD-UIP and 4 out of 10 with CVD-NSIP tested positive (p<0.05). ER values were significantly lower in patients with IPF/UIP than idiopathic NSIP, CVD-UIP or CVD-NSIP (p<0.05). Among idiopathic NSIP, CVD-NSIP and CVD-UIP patients, the ER values did not differ. CONCLUSIONS: Among IIP patients, only those with idiopathic NSIP, not IPF/UIP, tested positive for AECA. The prevalence of AECA in idiopathic NSIP patients was similar to that in CVD-ILD patients. These results may provide important information to understand the distinct pathophysiology of each form of IIPs. PMID- 17851061 TI - Organometals of tin, lead and mercury compounds in landfill gases and leachates from Bavaria, Germany. AB - Organo-Sn, -Pb and -Hg compounds were monitored in gases and leachates of 11 municipal waste landfills and one hazardous waste landfill from Bavaria, Germany, with the objectives to estimate the methylation of Sn, Pb and Hg and to assess the risk of their release into the adjacent environment. In the gases, tetramethyl Sn predominated (>80% of total gaseous Sn) with concentrations up to 160 microg Sn m(-3). Dimethyl-Hg and tetramethyl-Pb were only occasionally detected with concentrations up to 2.9 and 2.1 microg m(-3) as Hg or Pb, respectively. In all leachates, trimethyl-Sn dominated with a maximum concentration of 2100 ng Sn L(-1). No organo-Pb compounds were found, and monomethyl-Hg was detected in only one leachate. The concentrations of trimethyl Sn were up to 100-fold higher in the condensate water than in leachates, and the concentrations of organo-Sn compounds were lower in the adjacent groundwater than in the corresponding leachates. The high abundance of methylated Sn species in the gases and leachates indicates Sn methylation, suggesting the landfill as a source for organo-Sn compounds. In comparison, methylation of Hg and Pb was of little importance, probably due to low Hg concentrations and low rates of Pb methylation in the landfill. The risks of organo-Sn compounds release to the adjacent air is low due to flaring of landfill gases. However, there is probable release of organo-Sn compounds, especially trimethyl-Sn, to the adjacent groundwater. PMID- 17851062 TI - An analytic network process model for municipal solid waste disposal options. AB - The aim of this paper is to present an evaluation method that can aid decision makers in a local civic body to prioritize and select appropriate municipal solid waste disposal methods. We introduce a hierarchical network (hiernet) decision structure and apply the analytic network process (ANP) super-matrix approach to measure the relative desirability of disposal alternatives using value judgments as the input of the various stakeholders. ANP is a flexible analytical program that enables decision makers to find the best possible solution to complex problems by breaking down a problem into a systematic network of inter relationships among the various levels and attributes. This method therefore may not only aid in selecting the best alternative but also helps decision makers to understand why an alternative is preferred over the other options. PMID- 17851063 TI - Study of thin biocovers (TBC) for oxidizing uncaptured methane emissions in bioreactor landfills. AB - Bioreactor landfills are designed to accelerate municipal solid waste biodegradation and stabilization; however, the uncaptured methane gas escapes to the atmosphere during their filling. This research investigates the implementation of a novel methane emission control technique that involves thin biocovers (TBC) placed as intermediate waste covers to oxidize methane without affecting the operation of bioreactor landfills. Batch incubation experiments were conducted for selecting the optimum TBC materials, capable of oxidizing methane to carbon dioxide by methanotrophic bacteria. Column experiments were performed to investigate the TBC performance under varying moisture content, compost-to-sawdust ratio, methane flow rate, and biocover thickness. Overall, the optimum TBC is comprised of a 30-cm thick bed of 0-10mass% sawdust mixed with compost, having a moisture content of 52% ww, which showed 100% CH4 oxidation efficiency over an extended period of time even at a relatively high methane inlet load of 9.4gm(-3)h(-1). PMID- 17851064 TI - Landfill gas upgrading with countercurrent water wash. AB - A pilot-scale countercurrent absorption process for upgrading landfill gas to produce vehicle fuel was studied using absorption and desorption units and water as absorbent. The height-to-diameter ratio of the absorption column used was 3:1 instead of the more conventionally used 20:1 ratio, and a higher pressure was used along with a lower water flow rate. The effects of pressure (10-30 bar) and water and gas flow-ratios on the upgrading process were studied. Methane content in the product gas increased to near or above 90% with both gas flows (50 and 100 l/min) used at over 20 bar pressure with 10 l/min water flow and at 30 bar pressure with 5l/min water flow. Carbon dioxide content with these upgrading parameters ranged from 3.2% to 4.8%. The remaining fraction of the product gas was nitrogen (from 6% to 7%), while hydrogen sulphide was removed to below the detection limit with all of the upgrading parameters used. The methane content of exhaust gas increased with increasing pressure. In conclusion, the pilot-scale gas upgrading process studied here appears to be able to produce gas with high energy content (>90% methane), apparently suitable as vehicle fuel, from landfill gas. PMID- 17851065 TI - Slurry phase bioremediation of PAHs in industrial landfill samples at laboratory scale. AB - The effect of Tween 80 and selected bacteria additions on the bioremediation of PAH contaminated landfill soil (70.38mgkg(-1)) was evaluated in a slurry phase bioreactor. A phenanthrene-degrading consortium was selected by enrichment cultures and used as autochthonous inoculum. The Tween 80 addition increased the aqueous concentration of both high and low molecular weight PAHs. In the experiment with Tween 80 and inoculum addition, added microorganisms improved (>90%) the biodegradation of two- and three-ring PAHs as well as of the four-ring PAHs pyrene and fluoranthene. Biodegradation of the higher molecular weight PAHs was about 30% in experiments with Tween 80 addition, with and without inoculum addition. PMID- 17851066 TI - Variations of metal distribution in sewage sludge composting. AB - In the study, the variations of heavy metal distributions (of Cu, Mn, Pb, and Zn) during the sewage sludge composting process were investigated by sequential extraction procedures. The total content of Cu and Zn in the composted mixture increased after the composting process. Mn and Zn were mainly found in mobile fractions (exchangeable fraction (F1), carbonate fraction (F2), and Fe/Mn oxide fraction (F3)). Cu and Pb were strongly associated with the stable fractions (organic matter/sulfides fraction (F4) and residual fraction (F5)). These five metal fractions were used to calculate the metal mobility (bioavailability) in the sewage sludge and composted mixture. The mobility (bioavailability) of Mn, Pb, and Zn (but not Cu) increased during the composting process. The metal mobility in the composted mixture ranked in the following order: Mn>Zn>Pb>Cu. PMID- 17851067 TI - A cytokine immunosensor for multiple sclerosis detection based upon label-free electrochemical impedance spectroscopy. AB - A biosensor for the serum cytokine, interleukin-12 (IL-12), based upon a label free electrochemical impedance spectroscopy monitoring is described. Overexpression of IL-12 has been correlated to the diagnosis of multiple sclerosis (MS). The prototype biosensor was fabricated on a disposable gold coated silver ribbon electrode by immobilizing anti-IL-12 monoclonal antibodies (mAbs) onto the surface of the electrode. This technique was advantageous as the silver electrodes provided a more rigid and conductive substrate than thin gold foil electrodes and helped in obtaining more reproducible data when used with the electrode holder. Results indicate that IL-12 can be detected at physiological levels, <100 fM with p<0.05 in a label-free and real-time manner. The cost effective approach described here can be used for diagnosis of diseases (like MS) with known biomarkers in body fluids and for monitoring physiological levels of biomolecules with healthcare, food, and environmental relevance. PMID- 17851068 TI - Perspectives on science and art. AB - Artists try to understand how we see, sometimes explicitly exploring rules of perspective or color, visual illusions, or iconography, and conversely, scientists who study vision sometimes address the perceptual questions and discoveries raised by the works of art, as we do here. PMID- 17851069 TI - Chemical probes shed light on protein function. AB - Site-specific protein labeling with synthetic dyes is an emerging technique for live cell imaging. A protein or peptide tag fused to the protein of interest provides the means for attachment of a fluorophore or other small molecule probe, to allow non-invasive imaging of the dynamics of protein localization. The past two years have seen significant advances in such methods, the publication of a number of new tags for labeling, and the imaginative application of established techniques to tackle previously intractable biological questions. PMID- 17851070 TI - Single-particle reconstruction from EM images of helical filaments. AB - Helical filaments were the first structures to be reconstructed in three dimensions from electron microscopic images, and continue to be extensively studied due to the large number of such helical polymers found in biology. In principle, a single image of a helical polymer provides all of the different projections needed to reconstruct the three-dimensional structure. Unfortunately, many helical filaments have been refractory to the application of traditional (Fourier-Bessel) methods due to variability, heterogeneity, and weak scattering. Over the past several years, many of these problems have been surmounted using single-particle type approaches that can do substantially better than Fourier Bessel approaches. Applications of these new methods to viruses, actin filaments, pili and many other polymers show the great advantages of the new methods. PMID- 17851071 TI - Insulin receptor structure and its implications for the IGF-1 receptor. AB - The insulin receptor (isoforms IR-A and IR-B) and the type-I insulin-like growth factor receptor (IGF-1R) are homologous, multi-domain tyrosine kinases that bind insulin and IGF-1 with differing specificity. IR is involved in metabolic regulation and IGF-1R in normal growth and development. IR-A also binds IGF-2 with an affinity comparable to IGF-1R and, like the latter, is implicated in a range of cancers. The recent structure of the IR ectodomain dimer explains many features of ligand-receptor binding and provides insight into the structure of the intact ligand-binding site in both receptors. The structures of the L1-CR-L2 fragments of IR and IGF-1R reveal major differences in the regions that govern ligand specificity. The IR ectodomain X-ray structure raises doubts about that obtained by STEM reconstruction. PMID- 17851072 TI - Impacts of sterilization, microwave and ultrasonication pretreatment on hydrogen producing using waste sludge. AB - Hydrogen production by sterilization, microwave and ultrasonication pretreated waste sludge was investigated in this study. A new strain of Pseudomonas sp. GZ1 (EF551040) was inoculated in pretreated waste sludge to produce hydrogen. The experimental results showed that different pretreated sludge had evident differences in the yield of hydrogen production and lag time. Sterilized sludge had the largest yield of hydrogen production, and the maximum yield was 15.02 ml/gTCOD. The lag time of using sterilized sludge was 15 h, longer than other two pretreated sludge. Using the ultrasonicated sludge, the hydrogen production yield was smallest and lag time was shortest in the three pretreated sludge. Protein and carbohydrate could be released from waste sludge by pretreatment. Protein was the main nutrient used for hydrogen production. The concentration of protein, carbohydrate and SCOD increased after pretreatment and fermentation. The impacts of different pretreatments on hydrogen production were also discussed in detail. PMID- 17851073 TI - Structure-activity relationship (SAR) investigations of substituted imidazole analogs as TRPV1 antagonists. AB - A novel series of 4,5-biarylimidazoles as TRPV1 antagonists were designed based on the previously reported 4,6-disubstituted benzimidazole series. The analogs were evaluated for their ability to block capsaicin- or acid-induced calcium influx in TRPV1-expressing CHO cells. These studies led to the identification of a highly potent and orally bioavailable TRPV1 antagonist, imidazole 33. PMID- 17851074 TI - Synthesis and TNF expression inhibitory properties of new thalidomide analogues derived via Heck cross coupling. AB - A library of new thalidomide analogues containing an olefin functionality were synthesised using a Heck cross coupling reaction from their aryl halogenated precursor. All analogues were tested for their ability to inhibit the synthesis of the proinflammatory cytokine Tumour Necrosis Factor (TNF). Compounds 22, 29, 33 and 37 were the most effective in this assay inhibiting TNF expression 50%, 69%, 52% and 50%, respectively. PMID- 17851075 TI - Inactivation of soybean sterol 24-C-methyltransferase by elongated sterol side chains at C26. AB - The enzymatic C-methylation reaction catalyzed by the Glycine max sterol 24-C methyltransferase was studied with substrate analogs containing a cycloartenol nucleus (CA) and a double bond (8) or triple bond (14) attached to C26. The production of the corresponding C24(28)-methylene olefin and time-dependent inhibition kinetics of k(inact) 0.24 min(-1) (CA-8) or 0.06 min(-1) (CA-14) indicates an active-site directed process and partitioning to produce novel products. PMID- 17851076 TI - 4-arylcyclohexylalanine analogs as potent, selective, and orally active inhibitors of dipeptidyl peptidase IV. AB - A novel series of 4-arylcyclohexylalanine DPP-4 inhibitors was synthesized and tested for inhibitory activity as well as selectivity over the related proline specific enzymes DPP-8 and DPP-9. Optimization of this series led to 28 (DPP-4 IC(50)=4.8 nM), which showed an excellent pharmacokinetic profile across several preclinical species. Evaluation of 28 in an oral glucose tolerance test demonstrated that this compound effectively reduced glucose excursion in lean mice. PMID- 17851077 TI - Prospective evaluation of concomitant tumour bed boost with whole breast irradiation in patients with locally advanced breast cancer undergoing breast conserving therapy. AB - BACKGROUND AND PURPOSE: To evaluate prospectively the feasibility of concomitant weekly tumour bed electron boost along with whole breast radiotherapy (RT) following breast-conserving therapy (BCT) in patients with locally advanced breast cancer (LABC) with the aim of reducing overall treatment time. MATERIALS AND METHODS: Thirty patients with LABC suitable for BCT following neoadjuvant chemotherapy (CAF/CEF) were accrued in the study. Conventional RT (CRT) to the whole breast was delivered 5 days a week to a dose of 50Gy using 6-10MV photons. In addition, an electron boost to the tumour bed was delivered every Saturday, eventually delivering 5 such weekly fractions to a boost dose of 12.5Gy. Patients were evaluated for acute reactions during the treatment and cosmetic evaluation was done before, at the end of radiation therapy and at follow up by 2 independent observers blinded to each other. The study population (concomitant boost (CB) group) was compared with a similar cohort of 32 patients treated conventionally with tumour bed boost of 15Gy in 6 fractions delivered after the completion of whole breast irradiation (CRT group). RESULTS: All patients completed RT within the stipulated time with no grade IV skin toxicity in either group. At conclusion of RT, in the CB group, confluent moist desquamation (grade III) developed within the tumour bed region in 1 patient (3.3%) and outside tumour bed region in 3 patients (10%). In the CRT group, 3 and 4 patients (9.4% and 12%) developed moist desquamation within and outside the tumour bed regions, respectively. CB did not affect the global cosmesis as compared with CRT group (p=0.23) at the end of 3 years. CONCLUSION: Concomitant tumour bed boost along with whole breast RT appears to be safe and feasible in a select group of patients. As the treatment is completed earlier by 6-10 days than conventional practice, it has favourable time and resource implications, particularly attractive for patients travelling long distances for treatment. Based on these encouraging results, we are planning to confirm the results in an appropriately designed and powered randomised trial. PMID- 17851078 TI - Mitochondria-endoplasmic reticulum choreography: structure and signaling dynamics. AB - Mitochondria and endoplasmic reticulum (ER) have different roles in living cells but they interact both physically and functionally. A key aspect of the mitochondria-ER relationship is the modulation of Ca(2+) signaling during cell activation, which thus affects a variety of physiological processes. We focus here on the molecular aspects that control the dynamics of the organelle organelle interaction and their relationship with Ca(2+) signals, also discussing the consequences that these phenomena have, not only for cell physiology but also in the control of cell death. PMID- 17851079 TI - Design, synthesis and biological evaluation of novel lipoamino acid-based glycolipids for oral drug delivery. AB - A series of lipoamino acid-based glycolipids were synthesised. Suitably derivatised lipoamino acid derivatives were prepared and conjugated to monosaccharides (including glycosyl azides, isothiocyanates, thiols and sulphones) to yield novel O-, N-, S- and C-linked glycolipids in good yields. Their potential to improve the oral absorption of piperacillin is reported. PMID- 17851080 TI - A new opioid designed multiple ligand derived from the micro opioid agonist endomorphin-2 and the delta opioid antagonist pharmacophore Dmt-Tic. AB - Opioid compounds with mixed micro agonist/delta antagonist properties could be used as analgesics with low propensity to induce tolerance and dependence. Here we report the synthesis of a new designed multiple ligand deriving from the micro selective agonist endomorphin-2 and the delta selective antagonist pharmacophore Dmt-Tic. As predicted, the resulting bivalent ligand showed a micro agonist/delta antagonist profile deriving from the corresponding activities of each pharmacophore. PMID- 17851081 TI - Myricetin inhibits Escherichia coli DnaB helicase but not primase. AB - Primase and DnaB helicase play central roles during DNA replication initiation and elongation. Both enzymes are drug targets because they are essential, persistent among bacterial genomes, and have different sequences than their eukaryotic equivalents. Myricetin is a ubiquitous natural product in plants that is known to inhibit a variety of DNA polymerases, RNA polymerases, reverse transcriptases, and telomerases in addition being able to inhibit kinases and helicases. We have shown that myricetin inhibits Escherichia coli DnaB helicase according to a mechanism dominated by noncompetitive behavior with a K(i) of 10.0+/-0.5 microM. At physiological ATP concentration, myricetin inhibits E. coli DnaB helicase with an inhibitory concentration at 50% maximal (IC(50)) of 11.3+/ 1.6 microM. In contrast, myricetin inhibited E. coli primase at least 60-fold weaker than DnaB helicase and far weaker than any other polymerase. PMID- 17851082 TI - Synthesis and HMG CoA reductase inhibition of 4-thiophenyl quinolines as potential hypocholesterolemic agents. AB - A series of novel 4-thiophenyl quinoline-based mevalonolactone derivatives were synthesized from ethyl 6,7,8-trisubstituted-4-chloro-quinoline-3-carboxylates by several reactions and evaluated for their ability to inhibit the rat HMG CoA reductase in vitro. It was found that substitution with a variety of thiophenyl groups at position 4 in quinoline resulted in retention or enhancement of the inhibition and the preferable groups were 4-isopropyl-thiophenyl and 3-methoxy thiophenyl. (4R,6S)-6-[(E)-2-(6,7,8-trifluoro-4-isopropylthiophenyl-quinoline-3 yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (A16) and (4R, 6S)-6 [(E)-2-(6-fluoro-4,7-di-(3-methoxy-thiophenyl)-quinoline-3-yl)-ethenyl]-3,4,5,6 tetrahydro-4-hydroxy-2H-pyran-2-one (A23) were approximately three times more potent than rosuvastatin or pitavastatin in inhibiting HMG CoA reductase and selected as the hypocholesterolemic candidates for further evaluation. PMID- 17851083 TI - Preparation and antitubercular activities of alkylated amino alcohols and their glycosylated derivatives. AB - A series of N- and C-alkylated amino alcohols and of their protected galactopyranosyl derivatives was synthesized and evaluated for antitubercular activity. Five of these compounds displayed good activity, with a MIC below 12.5mug/mL. The presence of the carbohydrate slightly affected the antibacterial activity. PMID- 17851084 TI - Inhibitors of type III secretion in Yersinia: design, synthesis and multivariate QSAR of 2-arylsulfonylamino-benzanilides. AB - Compound 1, 2-(benzo[1,2,5]thiadiazole-4-sulfonylamino)-5-chloro-N-(3,4-dichloro phenyl)-benzamide, was identified as a putative type III secretion inhibitor in Yersinia, and the compound thus has a potential to be used to prevent or treat bacterial infections. A set of seven analogues was synthesized and evaluated in a type III secretion dependent reporter-gene assay with viable bacterial to give basic SAR. A second set of 19 compounds was obtained by statistical molecular design in the building block and product space and by subsequent synthesis. Evaluation in the reporter-gene assay showed that the compounds ranged from non active to compounds more potent than 1. Based on the data multivariate QSAR models were established and the final Hi-PLS model showed good correlation between experimentally determined % inhibition and the calculated % inhibition of the reporter-gene signal. PMID- 17851085 TI - Evaluation of different counting methods for use in radiochemical purity testing procedures for 99mTc-labelled radiopharmaceuticals. AB - The efficiency and accuracy of different methods for quality control of radiopharmaceutical preparations for diagnostic purpose were studied. The radiochemical purity of (99m)Tc Tetrafosmin, (99m)Tc Exametazime, (99m)Tc Sestamibi and (99m)Tc Oxidronate was evaluated by different thin layer chromatography systems, followed by cutting of the strips into two or three sections and by the measurement of radioactivity distribution by dose calibrator or gamma counter. In addition, to confirm the accuracy of these routine procedures, the strips were cut into a number of micro-sections (14-25) and each of them evaluated by the gamma counter. The three tested procedures gave similar results and revealed a good and comparable accuracy. The radioactivity measurement with the dose calibrator remains the most practicable because of the rapidity of execution. PMID- 17851086 TI - Enhanced tolerance to sulfur dioxide and salt stress of transgenic Chinese cabbage plants expressing both superoxide dismutase and catalase in chloroplasts. AB - To explore the possibility of overcoming the highly phytotoxic effect of SO(2) and salt stress, we introduced the maize Cu/ZnSOD and/or CAT genes into chloroplasts of Chinese cabbage (Brassica campestris L. ssp. pekinensis cv. Tropical Pride) (referred to as SOD, CAT and SOD+CAT plants). SOD+CAT plants showed enhanced tolerance to 400 ppb SO(2), and visible damage was one-sixth that of wild-type (CK) plants. In addition, when SOD+CAT plants were exposed to a high salt treatment of 200 mM NaCl for 4 weeks, the photosynthetic activity of the plants decreased by only 6%, whereas that of CK plants decreased by 72%. SOD plants had higher total APX and GR activities than CK plants. As expected, SOD plants showed levels of protection from SO(2) and salt stress that were moderately improved compared to CK plants. However, CAT plants showed inhibition of APX activity and provided only limited improvements in plant stress tolerance. Moreover, SOD+CAT plants accumulated more K(+), Ca(2+) and Mg(2+) and less Na(+) in their leaves compared with those of CK plants. These results suggest that the expression of SOD and CAT simultaneously is suitable for the introduction of increased multiple stress protection. PMID- 17851087 TI - Prospective study of interleukin-6 and the risk of malignant ventricular tachyarrhythmia in ICD-recipients--a pilot study. AB - OBJECTIVE: We investigated the relationship between interleukin-6 (IL-6) and the risk of experiencing spontaneous ventricular tachyarrhythmia (VT/VF) in patients with an implantable cardioverter-defibrillator (ICD). BACKGROUND: Cytokine levels predict outcome in patients with advanced heart failure and are elevated in patients with coronary artery disease (CAD). Regarding heart rhythm disturbances, proinflammatory activity could predict the occurrence of atrial fibrillation. There is no data on cytokine levels and the risk of spontaneous VT/VF. METHODS: IL-6 serum concentrations were determined at baseline and follow-up in 47 consecutive ICD-patients with CAD and idiopathic dilated cardiomyopathy (IDC). Data were prospectively correlated with VT/VF-incidence. RESULTS: Thirty-six patients (76.6%) suffered from CAD and 11 (23.4%) from IDC. Mean serum concentrations of IL-6 at baseline and at 9 months follow-up were 6.12+/-4.98 and 4.63+/-6.97. 88 spontaneous VT/VF-events occurred in 13/47 patients (27.7%). Patients with VT/VF had significantly higher IL-6 levels as compared to patients without VT/VF (8.96+/-5.97 vs. 5.04+/-4.16pg/ml at baseline (p =0.03), 7.8+/-4.88 vs. 3.42+/-6.32pg/ml at follow-up (p =0.01)). CONCLUSIONS: Elevated IL-6 serum concentrations were prospectively associated with an increased risk of spontaneous VT/VF-events in ICD-patients with CAD or IDC. These preliminary findings support a possible association of proinflammatory activity and an increased susceptibility to spontaneous VT/VF-events. PMID- 17851088 TI - Resource consumption and costs of treating pain in patients affected by cancer in a district of northeast Italy. AB - WHO declared that pain is a relevant problem in public health and that opioids are the gold standard therapy for the treatment of moderate to severe pain. The present retrospective, epidemiological, observational study is aimed to evaluate resource consumption therapy in patients treated with opioids and died with a diagnosis of cancer in Treviso, a district in northeast Italy. For the monetisation of resource consumed, the Italian National Health Service perspective was adopted. For each patient, resource monetized were drugs (opioids, NSAIDs and adjuvants), hospitalizations with cancer diagnosis, diagnostic examinations and laboratory tests. All databases were linked in order to obtain patient profile of resource consumption. A total of 935 patients were included in the study. The incident opioid prescribed were for 60% morphine, 37% fentanyl, and 2.5% buprenorphine. The average length of treatment with opioids was 105+/-73 days. Of the patients included in the study, 79% received an anti inflammatory drug (traditional NSAIDs and/or COX2 inhibitors), while 21% of patients treated with opioids never had an anti-inflammatory reimbursed prescription during the observation period. The average length of anti inflammatory treatment was 133+/-83 days. For the vast majority of prescribed anti-inflammatory drugs, the received daily dose (RDD) was widely greater then the defined daily dose (DDD) before and during treatment with opioids, while for opioids the RDD was in line with the revised DDD for fentanyl, and less than the DDD for morphine and buprenorphine. The total daily cost per patient before the first prescription of opioids was euro 11.36 while after the first prescription of opioids, it increased to euro 21.12. This study confirms the under utilization of opioids in Italy both in terms of dosages and length of therapy. PMID- 17851089 TI - The cytokine TNFalpha increases the proportion of DRG neurones expressing the TRPV1 receptor via the TNFR1 receptor and ERK activation. AB - TNFalpha is involved in the generation of hyperalgesia in pathological states such as neuropathy and inflammation. The pronociceptive action of TNFalpha may be mediated at least in part by activation of the TRPV1 receptor which transduces heat stimuli in primary nociceptive afferents and mediates thermal hyperalgesia. In the present study, we investigated in cultured dorsal root ganglion (DRG) neurones, the somata of primary afferent fibres, whether TNFalpha increases TRPV1 receptor expression. We found that long-term exposure of DRG neurones of both rat and mouse to TNFalpha significantly increased the proportion of DRG neurones expressing TRPV1 receptor-like immunoreactivity. This TNFalpha effect was abolished in mice DRG neurones when DRG cultures were obtained from tnfr1/2-/- and tnfr1-/-, but not from tnfr2-/- mice. Furthermore, we found that activation of ERK but not of p38 kinase or cyclooxygenases is critically involved in the TNFalpha-induced increase of TRPV1 receptor expression. PMID- 17851090 TI - The C-terminal PDZ-ligand motif of the neuronal glycine transporter GlyT2 is required for efficient synaptic localization. AB - The neuronal glycine transporter 2 (GlyT2) belongs to the large SLC6 family of Na+/Cl--dependent neurotransmitter transporters. At its extreme C-terminus, GlyT2 carries a type III PDZ domain binding motif (PDZ-ligand motif), which interacts with the PDZ domain protein syntenin-1. Here, we investigated the physiological role of the GlyT2 PDZ-ligand motif by a loss-of-function approach. Inactivation of the PDZ-ligand motif did not impair the localization, glycosylation and transport function of recombinant GlyT2 expressed in HEK293T cells. However, in transfected hippocampal neurons, the synaptic localization of GlyT2 was significantly reduced upon PDZ-ligand motif inactivation. Co-localization of GlyT2 with marker proteins of excitatory and inhibitory synapses was decreased by down to 50% upon PDZ-ligand motif deletion as compared to the wild-type protein. These data indicate that the C-terminal PDZ-ligand motif of GlyT2 plays an important role in transporter trafficking to and/or stabilization at synaptic sites. PMID- 17851091 TI - Parafoveal-on-foveal and foveal word priming are different processes: behavioral and neurophysiological evidence. AB - Parafoveal-on-foveal priming refers to the presentation of an item (the prime) in parafoveal vision followed by the presentation of an item (the target) in foveal vision. In natural reading, the 'parafoveal preview benefit' subserves fluent reading as, e.g., reading times increase when such information is not available. Yet, the neural correlates of reading are mostly studied with foveally presented stimuli and little is known of this parafoveal influence. Here, we used complementary information from a behavioral study and a magnetoencephalography experiment to clarify the relationship between parafoveal-on-foveal and foveal priming. Unlike foveal priming, parafoveal-on-foveal priming was present only at short prime-to-target delay (<100 ms). Behaviorally, the parafoveal priming effect was influenced by the prime visual field (left/right) and target lexical type (word/non-word), suggesting emphasis on perceptual analysis for LVF primes and on conceptual analysis for RVF primes. At the neural level, the overall sequence of activation was similar for foveal and parafoveal primes followed by foveal word targets, but the priming effects were bilateral for foveal primes versus left-lateralized for RVF primes. No neural effects of priming appeared for LVF primes, in line with the RVF preference imposed by the Western writing system. These results highlight the role of the left hemisphere in linguistic analysis and point out possible limitations of foveal stimulus presentation for drawing conclusions about natural reading. PMID- 17851092 TI - Individual differences in mathematical competence predict parietal brain activation during mental calculation. AB - Functional neuroimaging studies have revealed that parietal brain circuits subserve arithmetic problem solving and that their recruitment dynamically changes as a function of training and development. The present study investigated whether the brain activation during mental calculation is also modulated by individual differences in mathematical competence. Twenty-five adult students were selected from a larger pool based on their performance on standardized tests of intelligence and arithmetic and divided into groups of individuals with relatively lower and higher mathematical competence. These groups did not differ in their non-numerical intelligence or age. In an fMRI block-design, participants had to verify the correctness of single-digit and multi-digit multiplication problems. Analyses revealed that the individuals with higher mathematical competence displayed stronger activation of the left angular gyrus while solving both types of arithmetic problems. Additional correlational analyses corroborated the association between individual differences in mathematical competence and angular gyrus activation, even when variability in task performance was controlled for. These findings demonstrate that the recruitment of the left angular gyrus during arithmetic problem solving underlies individual differences in mathematical ability and suggests a stronger reliance on automatic, language mediated processes in more competent individuals. PMID- 17851093 TI - Volumes, spatial extents and a probabilistic atlas of the human basal ganglia and thalamus. AB - The basal ganglia and thalamus are involved in processing all physiological behaviors and affected by many diseases. Accurate localization is a crucial issue in neuroimaging, particularly when working with groups of normalized images in a standard stereotaxic space. Here, manual delineation of the central structures (thalamus; nucleus caudatus and accumbens; putamen, pallidum, substantia nigra) was performed on 30 high resolution MRIs of healthy young adults (15 female, median age 31 years) in native space. Protocol inter-rater reliabilities were quantified as structure overlap (similarity indices, SIs). Structural volumes were calculated in native space, and after spatial normalization to stereotaxic space (MNI/ICBM152) and in relation to hemispheric volumes. Spatial extents relative to the anterior commissure (AC) were extracted. The 30 resulting atlases were then used to create probabilistic maps in stereotaxic space. Inter-rater SIs were high at 0.85-0.92 except for the nucleus accumbens. In native space, caudate, nucleus accumbens and putamen were significantly larger on the left, and the globus pallidus larger in males. After normalizing for brain volume, the nucleus accumbens, putamen and thalamus were larger on the left, with the gender difference in the globus pallidus still detectable. Some of these volume differences translated into significantly different distances from the AC. The probabilistic maps showed that overall the central structures' boundaries are relatively unchanged after spatial normalization. We present a comprehensive assessment of thalamic and basal ganglia volumetric and geometric data in both native and stereotaxic spaces. Probabilistic maps in MNI/ICBM152 space will allow accurate localization in group analyses. PMID- 17851095 TI - Short-term effects of energy changes on plasma leptin concentrations and glucose tolerance in healthy ponies. AB - To determine whether plasma leptin concentrations and glucose tolerance are affected by changes in energy balance, nine healthy Shetland ponies were fed at 140% followed by 75% of their maintenance requirements for 13 days in each of the two periods. Bodyweight was recorded every three days. Blood samples were taken every two days and analysed for leptin and cortisol. An oral glucose tolerance test was performed on day 7 of each period. Serial blood samples were analysed for glucose and insulin. Although bodyweight was not affected, plasma leptin concentrations increased (P<0.001) initially during overfeeding, but returned to previous values after 7 days. During underfeeding, plasma leptin concentrations decreased (P<0.001). Underfeeding was associated with a higher AUC for plasma glucose (P=0.02) and plasma insulin (P=0.05) resulting in a decreased glucose tolerance (AUC glucose/AUC insulin; P=0.008), probably due to a plasma cortisol increase caused by the reduced feed intake. It is concluded that changes in energy balance, without altering bodyweight, can influence plasma leptin concentrations in ponies. PMID- 17851094 TI - CMV-specific T cell therapy. AB - Human cytomegalovirus (CMV) infection continues to be one of the most important and life threatening complications after allogeneic stem cell transplantation (SCT). The reconstitution of CMV-specific T cell responses after SCT has been demonstrated to be protective against the development of CMV disease. To improve T cell immunity against CMV in bone marrow transplant patients, different strategies were explored. On one hand, CMV-specific T cells can be selected from the donor, and can be transferred to the patient without any further in vitro expansion. On the other hand, CMV-specific T cells can be activated and expanded in vitro by stimulation with antigen presenting cells (APCs) loaded with specific proteins or peptides. Here, we review the therapeutic application of CMV-specific T cells to fight CMV infection. PMID- 17851096 TI - The pharmacokinetics and metabolism of ivermectin in domestic animal species. AB - The pharmacokinetic properties of drugs are closely related to their pharmacological efficacy. The kinetics of ivermectin are characterised, in general terms, by a slow absorption process, a broad distribution in the organism, low metabolism, and slow excretion. The kinetics vary according to the route of administration, formulation, animal species, body condition, age, and physiological status, all of which contribute to differences in drug efficacy. Characterisation of ivermectin kinetics can be used to predict and optimise the value of the parasiticide effects and to design programmes for parasite control. This article reviews the pharmacokinetics of ivermectin in several domestic animal species. PMID- 17851097 TI - Significant rising antibody titres to influenza A are associated with an acute reduction in milk yield in cattle. AB - Sporadic cases of an acute fall in milk production, "milk drop", were investigated in a Holstein Friesian dairy herd in Devon. The investigation was a case control study with two controls per case. Paired blood samples demonstrated that rising antibody titres to human influenza A/England/333/80 (H1N1) and human influenza A/Eng/427/88 (H3N2) were associated with an acute fall in milk production. Rising titres to bovine respiratory syncytial virus (BRSV), bovine virus diarrhoea virus (BVD), infectious bovine rhinotracheitis (IBR) and parainfluenza virus 3 (PI3) were not associated with an acute fall in milk production. Cases with rises in antibody to influenza A had significantly higher respiratory scores and rectal temperatures than their controls. The mean loss of milk production for the cases with rises in antibody to influenza A compared to their controls was 159.9L. This study provides further evidence that influenza A persists in cattle and causes clinical disease. PMID- 17851098 TI - Internal thoracic artery-caudal epigastric artery as a collateral pathway in a dog with aortic occlusion: a case report. AB - Aortic occlusion is a rare vascular disorder in the dog. This report describes the clinical feature of an aged Boxer with complete occlusion of the abdominal aorta caused by an intraluminal thrombus. Angiography evidenced a collateral circulation, represented by the internal thoracic artery, the cranial epigastric artery and the caudal epigastric artery, providing adequate blood flow to the pelvis and pelvic limbs. This vascular network has only recently been recognised as one of the major collateral pathways for arterial blood supply to the pelvis and lower extremities in humans with chronic aorto-iliac occlusive disease (CAOD). Furthermore, a femoral artery Doppler waveform, characterised by low amplitude, a monophasic systolic wave with blunted parabolic flow profile and a small spectral window, peculiar to humans with CAOD, is documented for the first time in a dog with aortic occlusion. PMID- 17851099 TI - Isolation and characterisation of cancer stem cells from canine osteosarcoma. AB - There is increasing evidence that cancer is a stem cell disease. This study sought to isolate and characterise cancer stem cells from canine osteosarcoma. One human and three canine cell lines were cultured in non-adherent culture conditions using serum-starved, semi-solid media. Primitive sarcosphere colonies from all cell lines were identified under these conditions and were characterised using molecular and cytochemical techniques for embryonic stem cell markers. Expression of the embryonic stem cell-associated genes Nanog, Oct4 and STAT3 indicated a primitive phenotype. Sarcospheres could be reproduced consistently when passaged multiple times and produced adherent cell cultures when returned to normal growth conditions. Similarities between human and canine osteosarcoma cell lines add credence to the potential of the dog as a model for human disease. PMID- 17851100 TI - How long will equestrian traditionalism resist science? PMID- 17851101 TI - Virucidal efficacy of nine commercial disinfectants against porcine circovirus type 2. AB - A number of commercially available disinfectants are commonly used on pig breeding farms and are authorised by the French Agricultural Ministry. However, the efficacy of these disinfectants is unknown with regard to the emergent porcine circovirus type 2 (PCV2). The virucidal efficacy of nine disinfectants was evaluated by testing a suspension of PCV2 isolated in France. The assays were performed at 20 degrees C and the efficacy determined after 30 min contact time between virus and disinfectant. After this time, the mixture was passed through a detoxification column and then diluted to remove compounds toxic to the virus and the porcine kidney cell line. The filtrate was serially diluted and inoculated onto cell culture. The infectivity of PCV2 was determined by an immunoperoxidase monolayer assay. No reduction in PCV2 titre was demonstrated with iodine and phenolic products. Significant PCV2 titre reductions (1.61 log(10)) were noted for the seven other products. For five disinfectants, namely a product composed of potassium monopersulfate, two products comprising a quaternary ammonium with one or three aldehyde(s), sodium hypochlorite, and sodium hydroxide, the concentration that significantly reduced the PCV2 titre was equal or 1.5-4 times lower than the authorised use concentration. Only two disinfectants, one composed of potassium monopersulfate, the other containing peracetic acid with hydrogen peroxide, reduced the PCV2 titre with a product concentration at best equal or two times higher than the authorised use concentration. PMID- 17851102 TI - Give a dog a genome. AB - In 2004 the dog became only the fifth mammal to have its entire genome fully sequenced. The canine genome was sequenced in the hope that it would help scientists understand the complex evolutionary mechanisms that shape genes and genomes and provide a powerful tool for identifying genetic factors that contribute to human health and disease. It is expected that over the coming years the genome of man's best friend will help in the understanding of the genetic cause of many inherited diseases that humans and dogs have in common. Not only of obvious benefit to humans, these studies will enable the development of DNA diagnostic tests that breeders can use to identify which of their dogs carry mutations that put them at risk of developing particular conditions and thus, over time, eliminate those diseases from the breed. PMID- 17851103 TI - Spectroscopic imaging with volume selection by unpaired adiabatic pi pulses: theory and application. AB - In NMR spectroscopy, volume selection can be advantageously achieved using adiabatic pi pulses, which enable high bandwidth and B(1) insensitivity. In order to avoid the generation of non-linear phase profiles and the subsequent signal loss caused by incoherent averaging, adiabatic pi pulses are usually used in pairs for volume selection in each spatial dimension. Alternatively, when performing spectroscopic imaging (SI), a high enough spatial resolution results in negligible phase dispersion within each pixel. This allows using only one pulse per selected spatial dimension, resulting in a reduced echo-time and reduced power deposition. In this work, the feasibility of such an approach is explored theoretically and numerically, allowing the derivation of explicit conditions to obtain SI images without artifact. Adequate spatial and spectral post-processing procedures are described to compensate for the effect of non linear phase profiles. These developments are applied to SI in the rat brain at 9.4 T, using a new adiabatic sequence named Pseudo-LASER. PMID- 17851104 TI - Stearoyl-CoA desaturase mRNA expression during bovine adipocyte differentiation in primary culture derived from Japanese Black and Holstein cattle. AB - Stearoyl-CoA desaturase (SCD) catalyzes the synthesis of monounsaturated fatty acids (MUFAs). In cattle, the MUFAs are related to softness and flavor of meat. In order to investigate gene expression profile during bovine preadipocyte differentiation, we isolated stromal-vascular cells from perirenal adipose tissues of Japanese Black and Holstein steers. Gene expression level of adipocyte type fatty acid binding protein (FABP4), SCD, sterol regulatory element binding protein 1 (SREBP1) and CCAAT/enhancer binding protein alpha (C/EBP-alpha) were elucidated by real-time PCR assay. The levels of SCD mRNA expression were significantly increased to 10.8 and 6.3-fold in Japanese Black and Holstein, respectively, on day 1 of the culture. The difference in SCD expression between the two breeds may reflect differences in the fat development characteristics of the cattle breeds. Although transcription factors SREBP1 and C/EBP-alpha are supposed to regulate SCD expression, expression levels of the two factors were not completely consistent with that of SCD. PMID- 17851105 TI - The ON-OFF dichotomy in visual processing: from receptors to perception. AB - Vision scientists long ago pointed to black and white as separate sensations and saw confirmation in the fact that in the absence of light, one perceives the visual field as gray against which the negative after-image of a bright light appeared blacker. The first recordings from optic nerve fibers in vertebrates revealed ON and OFF signals, later associated with separate streams, arising already at the synapse between receptors and bipolar cells. These can be identified anatomically and physiologically and remain distinct all the way to the lateral geniculate nucleus, whose fibers form the input to the primary visual cortex. The dichotomy has been probed by electroretinography and analyzed by means of pharmacological agents and dysfunction due to genetic causes. The bi- rather than a unidirectional nature of the retinal output has advantages in allowing small signals to remain prominent over a greater dynamic range. The two streams innervate cortical neurons in a push-pull manner, generating receptive fields with spatial sensitivity profiles featuring ON and OFF subregions. Manifestations of the dichotomy appear in a variety of simple visual discriminations where there are often profound threshold differences in patterns with same polarity as compared with mixed contrast-polarity components. But even at levels in which the spatial, contrast and color attributes have already been securely established and black and white elements participate equally, a categorical difference between blackness and whiteness of a percept persists. It is an opponency, akin to the ones in the color domain, derived from the original ON and OFF signals and subsequently bound with the other attributes to yield a feature's unitary percept. PMID- 17851106 TI - Subjective cognitive dysfunction associated with drug-induced parkinsonism in schizophrenia. AB - The authors investigated the subjective cognitive dysfunction associated with drug-induced parkinsonism (DIP) among 58 stabilized schizophrenic outpatients. Subjective cognitive dysfunction was comprehensively assessed using the Frankfurt Complaint Questionnaire (FCQ). Multivariate analysis revealed that the DIP group scored significantly higher on the total FCQ score than the non-DIP group. In phenomenological subscale scores, the DIP group had significantly higher scores on "deterioration of discrimination", "psychomotor disorder", and "perceptual disorder" than the non-DIP group. These results suggest that DIP is significantly associated with subjective cognitive-perceptual dysfunction, reflecting the complex nature of DIP that includes motor and cognitive aspects. PMID- 17851107 TI - Phosphorylation of Tat-interactive protein 60 kDa by protein kinase C epsilon is important for its subcellular localisation. AB - Tat-interactive protein 60 kDa is a nuclear acetyltransferase that both coactivates and corepresses transcription factors and has a definitive function in the DNA damage response. Here, we provide evidence that Tat-interactive protein 60 kDa is phosphorylated by protein kinase C epsilon. In vitro, protein kinase C epsilon phosphorylates Tat-interactive protein 60 kDa on at least two sites within the acetyltransferase domain. In whole cells, activation of protein kinase C increases the levels of phosphorylated Tat-interactive protein 60 kDa and the interaction of Tat-interactive protein 60 kDa with protein kinase C epsilon. A phosphomimetic mutant Tat-interactive protein 60 kDa has distinct subcellular localisation compared to the wild-type protein in whole cells. Taken together, these findings suggest that the protein kinase C epsilon phosphorylation sites on Tat-interactive protein 60 kDa are important for its subcellular localisation. Regulation of the subcellular localisation of Tat interactive protein 60 kDa via phosphorylation provides a novel means of controlling Tat-interactive protein 60 kDa function. PMID- 17851109 TI - Fragment-based screening using X-ray crystallography and NMR spectroscopy. AB - Approaches which start from a study of the interaction of very simple molecules (fragments) with the protein target are proving to be valuable additions to drug design. Fragment-based screening allows the complementarity between a protein active site and drug-like molecules to be rapidly and effectively explored, using structural methods. Recent improvements in the intensities of laboratory X-ray sources permits the collection of greater amounts of high-quality diffraction data and have been matched by developments in automation, crystallisation and data analysis. Developments in NMR screening, including the use of cryogenically cooled NMR probes and (19)F-containing reporter molecules have expanded the scope of this technique, while increasing the availability of binding site and quantitative affinity data for the fragments. Application of these methods has led to a greater knowledge of the chemical variety, structural features and energetics of protein-fragment interactions. While fragment-based screening has already been shown to reduce the timescales of the drug discovery process, a more detailed characterisation of fragment screening hits can reveal unexpected similarities between fragment chemotypes and protein active sites leading to improved understanding of the pharmacophores and the re-use of this information against other protein targets. PMID- 17851108 TI - LSD1 and the chemistry of histone demethylation. AB - The recent discovery that histone demethylation can be catalyzed by the flavin dependent amine oxidase LSD1 has ushered in a new chapter in the chromatin remodeling community. Herein, we discuss the rapid progress of the histone demethylase field including the recent identification of the non-heme iron dependent histone demethylases (JmjC family), the basis for LSD1 substrate site specificity and the newly emerging potential for inhibition of these enzymes in structural and functional analysis. PMID- 17851110 TI - How females become complex: cell differentiation in the gametophyte. AB - In contrast to animals, gametes in plants form a separate haploid generation, the gametophyte. The female gametophyte of flowering plants consists of just four different cell types that play distinct roles in the reproductive process. Differentiation of the distinct cell fates is tightly controlled and appears to follow regional cues that are arranged along a polar axis. Mutant analysis suggests that important aspects of gametophyte patterning are gametophytically regulated. Additionally, structural and molecular changes following misspecification indicate that the female gametophyte is a remarkably versatile structure with enormous respecification potential. Recently, new tools have been developed that open fascinating possibilities to access and analyze those processes that ultimately ensure successful fertilization. PMID- 17851111 TI - Molecular encounters at microtubule ends in the plant cell cortex. AB - The cortical arrays that accompany plant cell division and elongation are organized by a subtle interplay between intrinsic properties of microtubules, their self-organization capacity and a variety of cellular proteins that interact with them, modify their behaviour and drive organization of diverse, higher order arrays during the cell cycle, cell growth and differentiation. As a polar polymer, the microtubule has a minus and a plus end, which differ in structure and dynamic characteristics, and to which different sets of partners and activities associate. Recent advances in characterization of minus and plus end directed proteins provide insights into both plant microtubule properties and the way highly organized cortical arrays emerge from the orchestrated activity of individual microtubules. PMID- 17851112 TI - Ubiquitin ligases mediate growth and development by promoting protein death. AB - The ubiquitin proteasome system (UPS) allows plants to effectively and efficiently alter their proteome so as to ensure developmental plasticity and environmental adaptation. Recent work has demonstrated that the UPS is an integral part of multiple hormone-signaling pathways, which modulate cell growth and differentiation. In response to variation in hormone levels, the UPS regulates the abundance of signaling factors, mainly hormone-responsive transcription factors, which mediate cellular responses. Recent exciting studies have shown that hormones directly or indirectly modulate substrate ubiquitination by regulating E3-substrate interaction. Other avenues of regulation include regulating E3 mRNA abundance. PMID- 17851113 TI - Assessment of the genotoxicity of olive mill waste water (OMWW) with the Vicia faba micronucleus test. AB - The present study concerns the genotoxicity of olive mill waste water (OMWW) generated in mills producing olive oil in Morocco. The Vicia faba micronucleus test was used to evaluate the genotoxicity of OMWW and the six major phenolic compounds identified by HPLC in this effluent. Five dilutions of OMWW were tested: 0.1, 1, 5, 10 and 20%. Maleic hydrazide was used as a positive control. The results showed that OMWW was genotoxic at 10% dilution. In order to investigate the components involved in this genotoxicity, the six major phenols present in this effluent, oleuropein, gallic acid, 4-hydroxyphenyl acetic acid, caffeic acid, paracoumaric acid and veratric acid, were studied at concentrations corresponding to the genotoxic concentration of the OMWW itself. Two phenols, gallic acid and oleuropein induced a significant increase in micronucleus frequency in Vicia faba; the four other phenols had no significant genotoxic effect. These results suggest that under the experimental conditions of our assay, OMWW genotoxicity was associated with gallic acid and oleuropein. PMID- 17851114 TI - Different cytotoxic and clastogenic effects of epigallocatechin gallate in various cell-culture media due to variable rates of its oxidation in the culture medium. AB - Positive genotoxicity results are often observed using mammalian cells in culture with agents that are not in vivo genotoxins. We here illustrate one possible explanation: interaction of test chemicals with the cell-culture media used. We find that the toxicity and clastogenicity of epigallocatechin gallate (EGCG) to Chinese Hamster ovary (CHO) cells is affected by the culture medium used and appears largely or entirely due to variable rates of formation of hydrogen peroxide (H(2)O(2)) by chemical reactions of EGCG with the culture media. Catalase decreased EGCG toxicity substantially. Of seven different types of commonly used media evaluated, F-10 and F-12 nutrient mixtures were the least prone to produce this artefact. Although it generated H(2)O(2) in the culture media, ascorbate was not toxic to CHO cells because the H(2)O(2) levels achieved were insufficient to kill these cells. Thus, the culture medium, the cell type and the presence or absence of catalase (e.g. its variable amounts in S9 fractions) must be taken into account in in vitro genotoxicity testing. PMID- 17851115 TI - Protective action of melatonin against oxidative DNA damage: chemical inactivation versus base-excision repair. AB - Melatonin is a hormone-like substance that has a variety of beneficial properties as regulator of the circadian rhythm and as anti-inflammatory and anti-cancer agent. The latter activity can be linked with the ability of melatonin to protect DNA against oxidative damage. It may exert such action either by scavenging reactive oxygen species or their primary sources, or by stimulating the repair of oxidative damage in DNA. Since such type of DNA damage is reflected in oxidative base modifications that are primarily repaired by base-excision repair (BER), we tried to investigate in the present work whether melatonin could influence this DNA-repair system. We also investigated the ability of melatonin to inactivate hydrogen peroxide, a potent source of reactive oxygen species. Melatonin at 50 microM and its direct metabolite N(1)-acetyl-N(2)-formyl-5-methoxykynuramine reduced DNA damage induced by hydrogen peroxide at approximately the same ratio. Melatonin stimulated the repair of DNA damage induced by hydrogen peroxide, as assessed by the alkaline comet assay. However, melatonin at 50 microM had no impact on the activity in vitro of three glycosylases playing a pivotal role in BER: Endo III, Fpg and ANPG 80. On the other hand, melatonin chemically inactivated hydrogen peroxide, reducing its potential to damage DNA. And finally, melatonin did not influence the repair of an a-basic (AP) site by cellular extracts, as was evaluated by a functional BER assay in vitro. In conclusion, melatonin can have a protective effect against oxidative DNA damage by chemical inactivation of a DNA-damaging agent as well as by stimulating DNA repair, but key factors in BER, viz. glycosylases and AP-endonucleases, do not seem to be affected by melatonin. Further study with other components of the BER machinery and studies aimed at other DNA-repair systems are needed to clarify the mechanism underlying the stimulation of DNA repair by melatonin. PMID- 17851116 TI - Malaria infection modulates effects of genotoxic chemicals in the mouse bone marrow micronucleus test. AB - Malaria has been reported to modulate the activity of cytochrome-P450 enzymes (CYP). Since CYPs are involved both in the activation and detoxication of xenobiotics, we investigated whether malaria would modify the effects of chemical carcinogens in the bone-marrow micronucleus assay. Female C57BL6 mice were infected with Plasmodium berghei (ANKA) and treated (ip route) with cyclophosphamide (CPA, 25 mg/kg body weight), 7,12-dimethylbenz[a]anthracene (DMBA, 50mg/kg body weight) or ethyl methanesulfonate (EMS, 150 mg/kg body weight), on post-infection days 9-12 when parasitemia was > or =9% of RBC. Controls were age-paired non-infected mice. Bone marrows were sampled at 24 and 48 h (CPA), 24 h (EMS) or 48 h (DMBA) after treatment. The background incidence of polychromatic erythrocytes with micronuclei (MN-PCE) in malaria-infected mice was approximately twofold the background incidence in non-infected controls. Effects of indirect clastogens (CPA and DMBA) in the micronucleus assay were attenuated while the effect of EMS, a direct clastogen, was enhanced by infection. In a separate experiment, malaria was shown to decrease activities of ethoxy-(EROD, a marker for CYP1A) and benzyloxy-(BROD, CYP2B) resorufin-O dealkylases in liver microsomes. The foregoing findings are consistent with the hypothesis that malaria-caused attenuation of genotoxicity arose from a down modulation of CYP isoforms that convert CPA (CYP2B) and DMBA (CYP1A) into their active metabolites. PMID- 17851117 TI - Sensitivity of the erythrocyte micronucleus assay: dependence on number of cells scored and inter-animal variability. AB - Until recently, the in vivo erythrocyte micronucleus assay has been scored using microscopy. Because the frequency of micronucleated cells is typically low, cell counts are subject to substantial binomial counting error. Counting error, along with inter-animal variability, limit the sensitivity of this assay. Recently, flow cytometric methods have been developed for scoring micronucleated erythrocytes and these methods enable many more cells to be evaluated than is possible with microscopic scoring. Using typical spontaneous micronucleus frequencies reported in mice, rats, and dogs we calculate the counting error associated with the frequency of micronucleated reticulocytes as a function of the number of reticulocytes scored. We compare this counting error with the inter animal variability determined by flow cytometric scoring of sufficient numbers of cells to assure that the counting error is less than the inter-animal variability, and calculate the minimum increases in micronucleus frequency that can be detected as a function of the number of cells scored. The data show that current regulatory guidelines allow low power of the test when spontaneous frequencies are low (e.g., < or =0.1%). Tables and formulas are presented that provide the necessary numbers of cells that must be scored to meet the recommendation of the International Working Group on Genotoxicity Testing that sufficient cells be scored to reduce counting error to less than the inter-animal variability, thereby maintaining a more uniform power of detection of increased micronucleus frequencies across laboratories and species. PMID- 17851118 TI - Gene-mutation induction by arsenic compounds in the mouse lymphoma assay. AB - Arsenic compounds are generally considered as poor inducers of gene mutations. To investigate the mutagenicity of several arsenic compounds at the thymidine kinase (Tk) gene, a reporter gene for mutation induction, we used the mouse lymphoma assay (MLA). This test is widely applied and detects a broad spectrum of mutational events, from point mutations to chromosome alterations. The selected arsenic compounds were two inorganic (sodium arsenite and arsenic trioxide) and four organic compounds (monomethylarsonic acid, dimethylarsinic acid, tetraphenylarsenium and arsenobetaine). The results show that sodium arsenite, arsenic trioxide, monomethylarsonic acid and dimethylarsinic acid are mutagenic, showing a clear dose-response pattern. On the other hand, tetraphenylarsenium and arsenobetaine are not mutagenic. Inorganic arsenic compounds are the more potent agents producing significant effects in the micromolar range, while the mutagenic organic arsenic compounds induce similar effects but in the millimolar range. PMID- 17851119 TI - Modulation of gamma-ray-induced apoptosis in human peripheral blood leukocytes by famotidine and vitamin C. AB - To study the radioprotective effects of vitamin C and famotidine against radiation-induced apoptosis in human peripheral blood leukocytes, peripheral blood was obtained from six healthy volunteers including three males and three females. Twelve microlitres of blood sample diluted in 1 ml complete RPMI-1640 medium was irradiated with various doses of gamma-rays (4, 8 and 12 Gy) in the presence or absence of various doses of vitamin C and famotidine. After 48 and 72 h incubation in a 37 degrees C CO(2) incubator, neutral comet assay was performed for all samples. At least 1000 cells were analyzed for each sample for presence of apoptosis. Data were statistically evaluated using Mann-Whitney non-parametric and ANOVA tests. Results show a significant increase in apoptosis induction following gamma-irradiation with a dose dependent manner compared to controls (p<0.001). Presence of famotidine at 200 microg/ml produced a significant protective effect against radiation-induced apoptosis for various doses of radiation. Similar effects were observed for vitamin C at much lower doses (10 microg/ml). Dose reduction factor (DRF) calculated for famotidine treatment was about 1.5, and above 2 for vitamin C treatment. These results suggest that both vitamin C and famotidine suppresses radiation-induced apoptosis when used with various doses of gamma-irradiation (4-12 Gy) probably via *OH radical scavenging and an intracellular antioxidation mechanism. PMID- 17851120 TI - Metabolic activation of carcinogenic aristolochic acid, a risk factor for Balkan endemic nephropathy. AB - Aristolochic acid (AA), a naturally occurring nephrotoxin and carcinogen, is associated with tumor development in patients suffering from Chinese herbs nephropathy (now termed aristolochic acid nephropathy, AAN) and may also be a cause for the development of a similar type of nephropathy, the Balkan endemic nephropathy (BEN). Major DNA adducts [7-(deoxyadenosin-N6-yl)-aristolactam and 7 (deoxyguanosin-N2-yl)aristolactam] formed from AA after reductive metabolic activation were found in renal tissues of patients with both diseases. Understanding which human enzymes are involved in AA activation and/or detoxication is important in the assessment of an individual's susceptibility to this plant carcinogen. This paper reviews major hepatic and renal enzymes responsible for AA-DNA adduct formation in humans. Phase I biotransformation enzymes play a crucial role in the metabolic activation of AA to species forming DNA adducts, while a role of phase II enzymes in this process is questionable. Most of the activation of AA in human hepatic microsomes is mediated by cytochrome P450 (CYP) 1A2 and, to a lower extent, by CYP1A1; NADPH:CYP reductase plays a minor role. In human renal microsomes NADPH:CYP reductase is more effective in AA activation. Prostaglandin H synthase (cyclooxygenase, COX) is another enzyme activating AA in human renal microsomes. Among the cytosolic reductases, NAD(P)H:quinone oxidoreductase (NQO1) is the most efficient in the activation of AA in human liver and kidney. Studies with purified enzymes confirmed the importance of CYPs, NADPH:CYP reductase, COX and NQO1 in the AA activation. The orientation of AA in the active sites of human CYP1A1, -1A2 and NQO1 was predicted from molecular modeling and explains the strong reductive potential of these enzymes for AA detected experimentally. We hypothesized that inter-individual variations in expressions and activities of enzymes activating AA may be one of the causes responsible for the different susceptibilities to this carcinogen reflected in the development of AA-induced nephropathies and associated urothelial cancer. PMID- 17851121 TI - Resonance light-scattering spectrometric study of interaction between enzyme and MPA-modified CdTe nanoparticles. AB - This paper described a novel assay of enzyme based on the measurement of enhanced resonance light-scattering (RLS) signals resulting from the electrostatic and coordination interaction of functionalized CdTe nanoparticles with enzyme. The CdTe nanoparticles which were modified with 3-mercaptocarboxylic acid (MPA) have abundant carboxylic groups (COOH). So the nanoparticles are water-soluble, stable and biocompatible. At pH 8.3 phosphate buffered saline (PBS), the RLS signals of functionalized nano-CdTe are greatly enhanced by bromelain and papain in the region of 220-800 nm characterized by the peak around 318-314 nm, respectively. The optimization conditions of the reaction were also examined and selected. Under the selected conditions, the enhanced RLS intensity is linearly proportional to the concentration of bromelain and papain. The liner range is (0.09-0.9) x 10(-6)mol/L for bromelain and (0.048-0.702) x 10(-6)mol/L for papain. The influences of some foreign substances were also examined. This method can be applied to the determination of enzyme. PMID- 17851122 TI - C-bis-pivot lariat ethers: synthesis and spectral investigations on new 15- and 17-membered coronands containing dimethoxyphosphoryl groups. AB - The reactions of dibenzo-diaza crown ethers (coronands) (1 and 2) with dimethylphosphite led to the formation of the mixture of meso and racemic C-bis pivot lariat ethers (3 and 4) containing dimethoxyphosphoryl groups. We have failed to make the resolution of the mixture, nevertheless, the detailed characterization and spectral investigations of compounds 3 and 4 have been made by elemental analyses, FTIR, (1)H NMR, (13)C NMR, (31)P NMR, COSY, DEPT, HETCOR and HMBC spectral data. The salient features of the spectral data of these compounds have been presented. PMID- 17851123 TI - The luminescent carbon-bearing microinclusion enigma in the Kimi Unit, Rhodope, Greece: Raman microscopic point analyses and mapping with different lasers. AB - The Kimi Unit of the Rhodope Metamorphic Province (RMP), NE Greece, experienced ultrahigh-pressure metamorphism (UHPM), as documented by the unequivocal presence of diamond microinclusions in metapelitic garnet porphyroblasts. Certain peculiar lozenge-shaped 2-8 microm sized inclusions in diamond-bearing garnets reveal a broad composite and asymmetric triplet band (phase XXX) at approximately 1331 cm( 1) in their Raman spectra acquired with a 632.8 nm He-Ne laser, initially attributed to an sp(3)-hybridized C-polymorph. These have been meticulously re investigated by means of combined 2-wavelength (514.5 nm/632.8 nm laser) Raman microscopy. Raman mapping has been extensively employed in order to examine the spatial distribution of phase XXX and of other phases in these polyphase inclusions and to explore for additional Raman bands. The triplet band at approximately 1331 cm(-1) measured with the 632.8 nm laser shifts to much higher wavenumbers ( approximately 4966 cm(-1)) when excited with a 514.5 nm Ar(+) laser, proving that the XXX triplet is not a real Raman band but a luminescence one at approximately 691.1 nm. Numerous hypotheses on the nature of the mysterious phase XXX (e.g. Cr(3+)-bearing mineral, carbonate, C polymorph, gas, organic phase) are explored and discussed but all are shown to be unsatisfactory. It is suggested that XXX occurs as nanocrystals that luminesce strongly giving the appearance (in Raman maps) of being larger. PMID- 17851124 TI - Estimation of source infrared spectra profiles of acetylspiramycin active components from troches using kernel independent component analysis. AB - Kernel independent component analysis (KICA), a kind of independent component analysis (ICA) algorithms based on kernel, was preliminarily investigated for blind source separation (BSS) of source spectra profiles from troches. The robustness of different ICA algorithms (KICA, FastICA and Infomax) was first checked by using them in the retrieval of source infrared (IR), ultraviolet (UV) and mass spectra (MS) from synthetic mixtures. It was found that KICA is the most robust method for retrieval of source spectra profiles. KICA algorithm is subsequently adopted in the analysis of diffuse reflection IR of acetylspiramycin (ASPM) troches. It is observed that KICA is able to isolate the theoretically predicted spectral features corresponding to the ASPM active components, excipients and other minor components as different independent (spectral) component. A troche can be authenticated and semi-quantified using the estimated ICs. KICA is an useful method for estimation of source spectral features of molecules with different geometry and stoichiometry, while features belonging to very similar molecules remain grouped. PMID- 17851125 TI - Spectroscopic characterization of the 1-substituted 3,3-diphenyl-4-(2' hydroxyphenyl)azetidin-2-ones: application of (13)C NMR, (1)H-(13)C COSY NMR and mass spectroscopy. AB - The article deals with spectroscopic characterization of azetidin-2-ones. The presence of substituents like hydroxyl, fluoro, methoxy and benzhydryl, etc., on the azetidin-2-one ring significantly affects the IR absorption and (13)C NMR frequencies of the carbonyl group present in these compounds. The presence of an ester carbonyl group or too many methine protons in the molecule has been observed to limit the scope of IR and (1)H NMR spectroscopy in unambiguous assignment of the structure. The application of (13)C NMR, 2D NMR ((1)H-(13)C COSY) and mass spectroscopy in characterization of complex azetidin-2-ones is discussed. An application of the latter two techniques is described in deciding unequivocally between an azetidin-2-one ring and chroman-2-one ring structure for the product obtained by treatment of the 1-substituted 3,3-diphenyl-4-[2'-(O diphenylacyl)hydroxyphenyl]-2-azetidinones with ethanolic sodium hydroxide at room temperature. PMID- 17851126 TI - Prospective study of Human Bocavirus (HBoV) infection in a pediatric university hospital in Germany 2005/2006. AB - BACKGROUND: Human Bocavirus (HBoV), a new species of the genus parvovirus newly detected in 2005, seems to be a worldwide distributed pathogen among children with respiratory tract infection (prevalence 2%-18%). Recently published retrospective studies and one prospective birth cohort study suggest that HBoV primary infection occurs in infants. METHODS: Prospective single center study over one winter season (November 2005-May 2006) with hospitalized children without age restriction using PCR-based diagnostic methods. RESULTS: HBoV DNA was detected in 11 (2.8%) of 389 nasopharyngeal aspirates from symptomatic hospitalized children (median age 9.0 months; range: 3-17 months). RSV, HMPV, HCoV, and Influenza B were detected in 13.9% (n=54), 5.1% (n=20), 2.6% (n=10), and 1.8% (n=7), respectively. There was no influenza A DNA detected in any of the specimens. The clinical diagnoses were acute wheezing (bronchitis) in four patients, radiologically confirmed pneumonia in six patients (55%) and croup syndrome in one patient. In five to six patients with pneumonia, HBoV was the only pathogen detected. While no patient had to be mechanically ventilated, 73% needed oxygen supplementation. In four (36.4%) patients at least one other viral pathogen was found (plus RSV n=3; 27.3%; Norovirus n=1; 9.1%). CONCLUSION: HBoV causes severe respiratory tract infections in infants and young children. Its role as a copathogen and many other open questions has to be defined in further prospective studies. PMID- 17851127 TI - C-reactive protein and interleukin-18 levels in relation to coronary heart disease: prospective cohort study from Busselton Western Australia. AB - BACKGROUND: Elevated levels of inflammatory markers are associated with incident coronary heart disease (CHD), but it remains controversial whether these markers provide incremental predictive value to conventional risk factors. We investigated the relationship between C-reactive protein (CRP) and interleukin-18 (IL-18) levels and risk of CHD in men and women without initial cardiovascular disease. METHODS: A prospective case-cohort design over the period 1981-2001 involving 253 incident CHD cases and a random sub-cohort of 441 subjects was used. Cox proportional hazards regression was used to estimate the relative risks (RRs) of CHD for continuous and tertiles of CRP and IL-18 after controlling for conventional risk factors. RESULTS: The multivariate-adjusted RR of CHD associated with one unit increase in log CRP in the overall population was 1.29 (1.07, 1.55; trend P=0.008). Men and women in the top compared to bottom third of CRP distribution had an adjusted RR for CHD of 1.65 (1.03-2.65; P=0.036). The multivariate RR for continuous log IL-18 was 1.34 in men, 1.63 in women and 1.36 overall, and none reached statistical significance. CONCLUSIONS: Baseline CRP but not IL-18 levels are independently predictive of future CHD. However CRP provides only modest additional predictive value over conventional risk factors and the benefit of a prevention strategy based on CRP still needs to be established. PMID- 17851128 TI - Percutaneous closure of left ventricular free wall rupture with associated false aneurysm to prevent cardioembolic stroke. AB - Left ventricular (LV) false aneurysm is an uncommon complication of myocardial infarction. Conventional treatment mandates surgical repair but is associated with significant perioperative risk. We present a case of successful percutaneous closure of a LV false aneurysm in a patient at high operative risk who suffered cardioembolic stroke related to thrombus within the aneurysm. The primary aim of treatment was to prevent recurrent embolic event. PMID- 17851129 TI - Expression of choline kinase alpha to predict outcome in patients with early stage non-small-cell lung cancer: a retrospective study. AB - BACKGROUND: Adequate prognostic markers to predict outcome of patients with lung cancer are still needed. The aim of this study was to assess whether choline kinase alpha (ChoKalpha) gene expression could identify patients with different prognoses. ChoKalpha is an enzyme involved in cell metabolism and proliferation and has a role in oncogene-mediated transformation in several human tumours, including lung cancer. METHODS: 60 patients with non-small-cell lung cancer (NSCLC) who had undergone surgical resection in a single centre were enrolled into the study as the training group. We used real-time reverse-transcriptase PCR (RT-PCR) to measure ChoKalpha gene expression and analyse the association between ChoKalpha expression and survival in evaluable patients. Additionally, a second group of 120 patients with NSCLC from a different hospital were enrolled into the study as the validation group. We did an overall analysis of all 167 patients who had available tissue to confirm the cut-off point for future studies. The primary endpoints were lung-cancer-specific survival and relapse-free survival. FINDINGS: Seven of the 60 patients in the training group were not evaluable due to insufficient tissue. In the 53 evaluable patients, the cut-off for those with ChoKalpha overexpression was defined by receiver operator under the curve (ROC) methodology. 4-year lung-cancer-specific survival was 54.43% (95% CI 28.24-80.61) for 25 patients with ChoKalpha expression above the ROC-defined cut-off compared with 88.27% (75.79-100) for 28 patients with concentrations of the enzyme below this cut-off (hazard ratio [HR] 3.14 [0.83-11.88], p=0.07). In the validation group, six of the 120 enrolled patients were not evaluable due to insufficient tissue. For the other 114 patients, 4-year lung-cancer-specific survival was 46.66% (32.67-59.65) for those with ChoKalpha expression above the ROC-defined cut-off compared with 67.01% (50.92-81.11) for patients with concentrations of ChoKalpha below the cut-off (HR 1.87 [1.01-3.46], p=0.04). A global analysis of all 167 patients further confirmed the association between ChoKalpha overexpression and worse clinical outcome of patients with NSCLC: 4-year lung cancer-specific survival for ChoKalpha expression above the ROC-defined cut-off was 49.00% (36.61-60.38) compared with 70.52% (59.80-76.75) for those with concentrations of ChoKalpha below the cut-off (HR 1.98 [1.14-3.45], p=0.01). The overall analysis confirmed the cut-off for ChoKalpha expression should be 1.91 times higher than concentrations noted in healthy tissues when ChoKalpha is used as an independent predictive factor of relapse-free and lung-cancer-specific survival in patients with early-stage NSCLC. INTERPRETATION: ChoKalpha expression is a new prognostic factor that could be used to help identify patients with early-stage NSCLC who might be at high risk of recurrence, and to identify patients with favourable prognosis who could receive less aggressive treatment options or avoid adjuvant systemic treatment. New treatments that inhibit ChoKalpha expression or activity in patients with lung cancer should be studied further. PMID- 17851130 TI - Technical outcomes of sentinel-lymph-node resection and conventional axillary lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial. AB - BACKGROUND: The goals of axillary-lymph-node dissection (ALND) are to maximise survival, provide regional control, and stage the patient. However, this technique has substantial side-effects. The purpose of the B-32 trial is to establish whether sentinel-lymph-node (SLN) resection can achieve the same therapeutic goals as conventional ALND but with decreased side-effects. The aim of this paper is to report the technical success and accuracy of SLN resection plus ALND versus SLN resection alone. METHODS: 5611 women with invasive breast cancer were randomly assigned to receive either SLN resection followed by immediate conventional ALND (n=2807; group 1) or SLN resection without ALND if SLNs were negative on intraoperative cytology and histological examination (n=2804; group 2) in the B-32 trial. Patients in group 2 underwent ALND if no SLNs were identified or if one or more SLNs were positive on intraoperative cytology or subsequent histological examination. Primary endpoints, including survival, regional control, and morbidity, will be reported later. Secondary endpoints are accuracy and technical success and are reported here. This trial is registered with the Clinical Trial registry, number NCT00003830. FINDINGS: Data for technical success were available for 5536 of 5611 patients; 75 declined protocol treatment, had no SLNs removed, or had no SLN resection done. SLNs were successfully removed in 97.2% of patients (5379 of 5536) in both groups combined. Identification of a preincision hot spot was associated with greater SLN removal (98.9% [5072 of 5128]). Only 1.4% (189 of 13171) of SLN specimens were outside of axillary levels I and II. 65.1% (8571 of 13 171) of SLN specimens were both radioactive and blue; a small percentage was identified by palpation only (3.9% [515 of 13 171]). The overall accuracy of SLN resection in patients in group 1 was 97.1% (2544 of 2619; 95% CI 96.4-97.7), with a false-negative rate of 9.8% (75 of 766; 95% CI 7.8-12.2). Differences in tumour location, type of biopsy, and number of SLNs removed significantly affected the false-negative rate. Allergic reactions related to blue dye occurred in 0.7% (37 of 5588) of patients with data on toxic effects. INTERPRETATION: The findings reported here indicate excellent balance in clinical patient characteristics between the two randomised groups and that the success of SLN resection was high. These findings are important because the B-32 trial is the only trial of sufficient size to provide definitive information related to the primary outcome measures of survival and regional control. Removal of more than one SLN and avoidance of excisional biopsy are important variables in reducing the false-negative rate. PMID- 17851131 TI - Increased frequency of CD4(+)CD25(high) Treg cells inhibit BCG-specific induction of IFN-gamma by CD4(+) T cells from TB patients. AB - Cell-mediated immunity plays a considerable role in the protection against Mycobacterium tuberculosis infection. The immune response to tuberculosis (TB) was dominated by both CD4(+) T cells with the T helper 1 type cytokines and CD8(+) T cells. Recent studies have suggested that the circumstances in which protective or tissue-damaging T cell responses to microbes are affected by the activity of Treg (CD4(+)CD25(high)) cells. In the present study, we demonstrated that the frequencies of CD4(+)CD25(+) and CD4(+)CD25(high) T cells in TB patients were significantly higher compared to normal individuals. These Treg cells expressed CTLA-4 and Foxp3 at protein level and displayed activation and memory phenotypes as assessed by flow cytometric analysis. The frequencies of CD4(+)CD25(high)CTLA-4(+) and CD4(+)CD25(high)Foxp3(+) T cells within the total CD4(+) T cell population were significantly increased in the blood of TB patients compared to healthy donors. Moreover, the expression of GITR on Treg cells was higher in TB patients than in normal donors. The phenotypic analysis demonstrated that CD4(+)CD25(high) Treg expressed higher levels of CD45RO and HLA-DR, and lower levels of CD45RA compared to CD4(+)CD25(low) and CD4(+)CD25(-) T cells. The addition of CD4(+)CD25(high) T cells back to cultures could significantly suppress the antigen-specific production of IFN-gamma induced by BCG-stimulated CD4(+)CD25(-) T cells, suggesting that Treg might play a key role in the control of cellular immune responses in TB infection. PMID- 17851132 TI - Femoral versus antecubital vein contrast injection. PMID- 17851133 TI - Transesophageal guided left atrial positioning of a percutaneous ventricular assist device. AB - Cardiogenic shock in the setting of myocardial infarction continues to represent a high proportion of immediate mortality in this patient population, despite ongoing advances in thrombolytics, PCI, and medical management of AMI. We present a case of peri-MI cardiogenic shock necessitating deployment of a percutaneous ventricular assist device (pVAD). TEE guidance played a crucial role in optimal positioning of the venous cannula in the left atrium. PMID- 17851134 TI - Systolic aortic regurgitation. AB - Aortic regurgitation is normally a diastolic phenomenon. Echocardiographic images of systolic aortic regurgitation in a patient with atrial fibrillation and heart failure are presented, and haemodynamic interpretation is provided. PMID- 17851135 TI - Adjunctive therapy of uncontrolled partial seizures with levetiracetam in Australian patients. AB - OBJECTIVE: The goal of the work described here was to explore the efficacy, safety, and tolerability of adjunctive therapy with levetiracetam and associated changes in health-related quality of life in Australian patients with uncontrolled partial seizures. METHODS: A phase IV open-label 16-week clinical trial was undertaken. Patients received adjunctive levetiracetam, adjusted according to clinical response to a final daily dose of 1000-3000 mg. Seizure frequency and adverse events were recorded. A quality-of-life questionnaire (QOLIE-10-P) was administered at the start and end of therapy. RESULTS: The intention-to-treat population (N=152) experienced a median reduction in total seizure frequency of 57.7%. The 50% responder rate was 56.6%, and 12.5% of patients were free of seizures throughout the trial. Adverse events were mostly mild or moderate, leading to discontinuation in 9.9%. The most common adverse events were somnolence, fatigue, headache, and dizziness. Behavioral adverse events occurred in approximately one-quarter of patients, including two-thirds of those who withdrew because of adverse events. There was an improvement in the QOLIE-10-P score. CONCLUSION: Levetiracetam is effective and well tolerated when added to existing therapy in patients with uncontrolled partial seizures. PMID- 17851136 TI - Higher heart rate and reduced heart rate variability persist during sleep in chronic fatigue syndrome: a population-based study. AB - Autonomic nervous system (ANS) dysfunction has been suggested in patients with chronic fatigue syndrome (CFS). In this study, we sought to determine whether increased heart rate (HR) and reduced heart rate variability (HRV) parameters observed in CFS patients during wakefulness persist during sleep. To this end, we compared heart rate (HR) and HRV as indicators of ANS function in CFS subjects and non-fatigued (NF) controls in a population-based, case-control study. Thirty subjects with CFS and 38 NF controls, matched for age-, sex- and body mass index, were eligible for analysis. Main outcome measures included mean RR interval (RRI), HR, and HRV parameters derived from overnight ECG. Plasma aldosterone and norepinephrine levels, medicines with cardiovascular effect, and reported physical activity were examined as covariates. General Linear Models were used to assess significance of associations and adjust for potential confounders. Compared to controls, CFS cases had significantly higher mean HR (71.4 vs 64.8 bpm), with a shorter mean RRI [840.4 (85.3) vs 925.4(97.8) ms] (p<0.0004, each), and reduced low frequency (LF), very low frequency (VLF), and total power (TP) of HRV (p<0.02, all). CFS cases had significantly lower plasma aldosterone (p<0.05), and tended to have higher plasma norepinephrine levels. HR correlated weakly with plasma norepinephrine (r=0.23, p=0.05) and moderately with vitality and fatigue scores (r=-0.49 and 0.46, respectively, p<0.0001). Limitation in moderate physical activity was strongly associated with increased HR and decreased HRV. Nevertheless, among 42 subjects with similar physical activity limitations, CFS cases still had higher HR (71.8 bpm) than respective controls (64.9 bpm), p=0.023, suggesting that reduced physical activity could not fully explain CFS associated differences in HR and HRV. After adjusting for potential confounders case-control differences in HR and TP remained significant (p<0.05). CONCLUSION: the presence of increased HR and reduced HRV in CFS during sleep coupled with higher norepinephrine levels and lower plasma aldosterone suggest a state of sympathetic ANS predominance and neuroendocrine alterations. Future research on the underlying pathophysiologic mechanisms of the association is needed. PMID- 17851137 TI - The distribution of HIV-1 recombination breakpoints. AB - We find that recombination breakpoints are non-randomly distributed across the genomes of HIV-1 intersubtype recombinants. In particular we find two recombination prone regions, "hot spots", located approximately either side of the envelope gene. To investigate this, we test whether there is a correlation between the distribution of the recombinant breakpoints with (1) genetic similarity, (2) predicted locations of secondary RNA structure, (3) regions identified as recombinant hot spots from experimental studies and (4) the predicted locations of positively selected sites. No detectable relationship with RNA secondary structure was found. A weak relationship with genetic similarity exists but it does not account for the recombination hot spots. The comparison with the published experimental studies indicated that the identified recombination hot spots differ in their locations, indicating that selection is having an impact on HIV-1 recombinant structures in infected individuals. We observe an association between recombination prone regions and strong positive selection across the envelope gene in support of this hypothesis. PMID- 17851138 TI - Turning off the G2 DNA damage checkpoint. AB - In response to DNA damage, cells activate checkpoints to delay cell cycle progression and allow time for completion of DNA repair before commitment to S phase or mitosis. During G2, many proteins collaborate to activate Chk1, an effector protein kinase that ensures the mitotic cyclin-dependent kinase remains in an inactive state. This checkpoint is ancient in origin and highly conserved from fission yeast to humans. Work from many groups has led to a detailed description of the spatiotemporal control of signaling events leading to Chk1 activation. However, to survive DNA damage in G2, the checkpoint must be inactivated to allow resumption of cell cycling and entry into mitosis. Though only beginning to be understood, here we review current data regarding checkpoint termination signals acting on Chk1 and its' upstream regulators. PMID- 17851139 TI - Fragile X repeats are potent inducers of complex, multiple site rearrangements in flanking sequences in Escherichia coli. AB - (CGG.CCG)n repeats induce the formation of complex, multiple site rearrangements and/or gross deletions in flanking DNA sequences in Escherichia coli plasmids. DNA sequence analyses of mutant clones revealed the influence of (a) the length (24, 44 or 73 repeats), (b) the orientation of the CGG.CCG region relative to the unidirectional origin, and (c) its transcription status. Complex rearrangements had occurred in the mutant clones since some products contained deletions, inversions and insertions and some products had only gross deletions. Furthermore, the CGG.CCG repeats repeatedly induced, up to 22 times, the formation of identical (to the bp) mutagenic products indicating the powerful nature of the complex processes involved. Also, the mutations were bidirectional from the CGG.CCG tract. The healed junctions had CG-rich microhomologies of 1 6bp, CG-rich regions and putative cruciforms and slipped structures. Hence, the fragile X syndrome mutagenic spectrum has been found, at least in part, in our model system. PMID- 17851141 TI - Simultaneous determination of gemcitabine and gemcitabine-squalene by liquid chromatography-tandem mass spectrometry in human plasma. AB - Gemcitabine-squalene is a new prodrug that self-organizes in water forming nanoassemblies. It exhibits better anti-cancer properties in vitro and in vivo than gemcitabine. A liquid chromatography/tandem mass spectrometry assay of gemcitabine-squalene and gemcitabine was developed in human plasma in order to quantitate gemcitabine and its squalene conjugate. After protein precipitation with acetonitrile/methanol (90/10, v/v), the compounds were analyzed by reversed phase high performance liquid chromatography and detected by tandem mass spectrometry using multiple reaction monitoring. The method was linear over the concentration range of 10-10,000 ng/ml of human plasma for both compounds with an accuracy lower than 10.4% and a precision below 14.8%. The method showed a lower limit of quantitation of 10 ng/ml of human plasma for dFdC and dFdC-SQ. A preliminary in vivo study in mice was shown as application of the method as no significant difference between human and mice plasma for the analysis of dFdC and dFdC-SQ was demonstrated. PMID- 17851140 TI - Effect of sildenafil on hypoxia-induced changes in pulmonary circulation and right ventricular function. AB - Hypoxia leads to pulmonary vasoconstriction in healthy men. However, the consequences on right ventricular function are not known. The effects of hypoxia on systolic pulmonary artery pressure (sPAP) and right ventricular function index (TEI) were assessed by Doppler echocardiography. Fourteen members of a Mount Everest expedition were monitored during acute hypoxic challenge at sea level, environmental hypoxia exposure at altitudes of 3440 m and 5245 m and 2 weeks after return to sea level. Subjects received either placebo or 50mg sildenafil in a double-blind randomised cross-over design. Under normoxia at baseline, mean sPAP was 17.1(S.E.M. 1.3) mm Hg, and TEI was 0.13(0.004). Both increased during acute hypoxia: sPAP 29.6(2.6) mm Hg, and TEI 0.35(0.06) (each p<0.01). At 5245 m sPAP was 29.1(1.7) and TEI was 0.43(0.05) in the placebo group, while in the sildenafil group, both sPAP and TEI were reduced to 22(1.5) mm Hg and 0.23(0.03) (each p<0.005), respectively. We conclude that in healthy individuals, exposure to acute hypoxia and sojourns at high altitude result in a small but significant increase in sPAP accompanied by an impairment of right ventricular function. Sildenafil significantly decreases sPAP and improves right ventricular function. PMID- 17851142 TI - Determination of 17-dimethylaminoethylamino-17-demethoxygeldanamycin in human plasma by liquid chromatography with mass-spectrometric detection. AB - An analytical method was developed and validated for the quantitative determination of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG; NSC707545), a novel heat shock 90 inhibitor, in human plasma. Calibration curves were linear in the concentration range of 1-500 ng/mL. Sample pretreatment involved a liquid-liquid extraction of 0.2 mL aliquots of plasma with ethyl acetate. 17-DMAG and the internal standard, beclomethasone, were separated on a Zorbax SB C18 column (75 mm x 2.1 mm, 3.5 microm), using a mobile phase composed of methanol and 0.2% formic acid (55:45, v/v). The column effluent was monitored by mass spectrometry with electrospray ionization. For the quality control samples at four different concentrations that were analyzed in quintuplicate, on four separate occasions, the accuracy and precision ranged from 93.8% to 99.5% and 1.4% to 3.3%, respectively. The assay modifications significantly improve upon our original, validated method. The developed method was subsequently applied to study the pharmacokinetics of 17-DMAG in a group of 23 patients. PMID- 17851143 TI - Isolation and purification of iridoid glycosides from Gardenia jasminoides Ellis by isocratic reversed-phase two-dimensional preparative high-performance liquid chromatography with column switch technology. AB - A two-dimensional column-switching system without sample loop trapping, where two columns were switched directly via a six-port two-position switching valve, was successfully applied for the first time to the isolation and purification of six iridoid glycosides including geniposide, gardenoside, shanzhiside, scandoside methyl ester, deacetyl-asperulosidic acid methyl ester and genipin-1-beta-D gentiobioside from Gardenia jasminoides Ellis, a plant used in the traditional Chinese medicine. The introduction of the six-port switching valve instead of sample loop assured 100% recovery from the first dimension to the second, and the injection volumes of the second dimension could reach 20 ml. In this mode of operation, the sample size of the two-dimensional approach was more than 1.3 times that of conventional gradient methods with even less solvent consumption. And the simultaneous operations of the two dimensions allowed the cycle time to be less than 19 min, compared with that (90 min) in the gradient elution single dimension mode of operation. All of the six isolated iridoid glycosides were isolated at high purities of over 99% with approximately 96% recoveries. PMID- 17851144 TI - Liquid chromatography-tandem mass spectrometric method for determination of mosapride citrate in equine tissues. AB - A simple method for determination of mosapride citrate and its metabolite, des-p fluorobenzyl mosapride (M-1), in equine muscle, liver, kidney, adipose tissue and intestine by liquid chromatography-tandem mass spectrometry has been developed. (+/-)-4-Amino-5-chloro-2-ethoxy-N-[[4-(2 chlorobenzyl)morpholinyl]methyl]benzamide was used as an internal standard. The analytes and internal standard were spiked and extracted from tissues by acetonitrile. The chromatographic separation was performed on a reversed-phase TSK-GEL SUPER ODS column with a mobile phase of acetonitrile-0.05% (v/v) formic acid containing 5 mmol/L nonafluoropentanoic acid (2:3, v/v). The method exhibited a large linear range from 0.0005 to 0.2 microg/mL for both mosapride citrate and M-1 (r>0.9976). In the intra-day assay (n=5), the relative standard deviations (RSDs) ranged from 1.1 to 7.8% for mosapride citrate and 1.6 to 7.2% for M-1. In the inter-day assay (n=3), the RSDs ranged from 1.0 to 13% for mosapride citrate and 0.8 to 11% for M-1. The extraction recovery at 1.28 microg/g of mosapride citrate from equine tissues ranged from 97 to 107%. The lower limit of quantification for mosapride citrate was found to be 0.004 microg/g. Stability studies were carried out at different storage conditions. The method reported is reliable, precise, and accurate and it has the capacity to be used for determination of mosapride citrate and its metabolite in tissue samples. PMID- 17851145 TI - Development and validation of a selective and sensitive bioanalytical procedure for the quantitative determination of gaboxadol in human plasma employing mixed mode solid phase extraction and hydrophilic interaction liquid chromatography with tandem mass spectroscopic detection. AB - A selective and sensitive hydrophilic interaction liquid chromatography tandem mass spectrometric bioanalytical method for the quantitative determination of gaboxadol in human heparinized plasma was developed and validated. Gaboxadol and the stable isotope labeled internal standard were extracted from plasma by mixed mode solid phase extraction and analyzed on an Asahipak NH2P HPLC column with a mobile phase composed of 70% acetonitrile and 30% ammonium acetate (20 mM, pH 4). The analytes were detected by a SCIEX API 4000 triple quadropole instrument using turbo electrospray ionization and multiple reaction monitoring negative mode. The method was validated over the concentration range of 0.5-100 ng/mL. The intra-day precision of the assay, as measured by the coefficient of variation (CV%), was within 4%. The intra-day assay accuracy was found to be within 2.2% of the nominal concentration for all the standards. The average recovery of gaboxadol was about 87% and the ion suppression was approximately 8%. To eliminate late eluters including the glucuronides, a "front cut" column switching procedure was added to the chromatographic system. The effectiveness of the column switching in eliminating the absolute matrix effect caused by late eluters was demonstrated by the low variation (CV<3.5%) in the peak areas of the internal standard during the assessment of the inter-day precision and accuracy and no significant relative matrix effect was observed as illustrated by the excellent intra-day precision (CV<1.5%) from the assessment of standard samples prepared in five different lots of control plasma. The described bioanalytical method has been successfully utilized for the analysis of gaboxadol in post-dose samples (>8000) from various clinical studies. Inter-day precision and accuracy were assessed from the daily mean (n=2) of QC values from 52 runs, i.e. more than 3000 samples. The inter-day precision of the assay, based on the coefficient of variation of QC, ranged from 2.1 to 5.1%. The inter-day assay accuracy was found to be within 4% of the nominal concentration for all QC samples. PMID- 17851146 TI - Liquid chromatography method for detecting native fluorescent bioamines in urine using post-column derivatization and intramolecular FRET detection. AB - Liquid chromatography (LC) with fluorescence detection is described for simultaneous determination of native fluorescent bioamines (indoleamines and catecholamines). This is based on intramolecular fluorescence resonance energy transfer (FRET) in an LC system following post-column derivatization of native fluorescent bioamines' amino groups with o-phthalaldehyde (OPA). OPA fluorescence was achieved through an intramolecular FRET process when the molecules were excited at maximum excitation wavelength of the native fluorescent bioamines. Bioamines separated by reversed-phase LC on ODS column were derivatized with OPA and 2-mercaptoethanol. This method provides sufficient selectivity and sensitivity for the determination of normetanephrine, dopamine, tyrosine, 5 hydroxytryptamine, tryptamine, and tryptophan in healthy human urine without prior sample purification. PMID- 17851147 TI - Improved endothelial cell adhesion and proliferation on patterned titanium surfaces with rationally designed, micrometer to nanometer features. AB - Previous in vitro studies have demonstrated increased vascular endothelial cell adhesion on random nanostructured titanium (Ti) surfaces compared with conventional (or nanometer smooth) Ti surfaces. These results indicated for the first time the potential nanophase metals have for improving vascular stent efficacy. However, considering the structural properties of the endothelium, which is composed of elongated vascular endothelial cells aligned with the direction of blood flow, it has been speculated that rationally designed, patterned nano-Ti surface features could further enhance endothelial cell functions by promoting a more native cellular morphology. To this end, patterned Ti surfaces consisting of periodic arrays of grooves with spacings ranging from 750 nm to 100 microm have been successfully fabricated in the present study by utilizing a novel plasma-based dry etching technique that enables machining of Ti with unprecedented resolution. In vitro rat aortic endothelial cell adhesion and growth assays performed on these substrates demonstrated enhanced endothelial cell coverage on nanometer-scale Ti patterns compared with larger micrometer scale Ti patterns, as well as controls consisting of random nanostructured surface features. Furthermore, nanometer-patterned Ti surfaces induced endothelial cell alignment similar to the natural endothelium. Since the re establishment of the endothelium on vascular stent surfaces is critical for stent success, the present study suggests that nanometer to submicrometer patterned Ti surface features should be further investigated for improving vascular stent efficacy. PMID- 17851148 TI - Selective cord coagulation in acardiac twins. AB - The twin reverse arterial perfusion (TRAP) sequence is a serious complication of monochorionic multiple pregnancies in which the affected twin is reversely perfused from the healthy co-twin, resulting in severely abnormal or absent cardiac development, severe malformations, and massive hydrops fetalis. The acardiac twin threatens the survival of the pump twin either by increasing the risk of congestive cardiac failure or by the development of polyhydramnios, preterm premature rupture of membranes, preterm labour and premature delivery. A wide spectrum of surgical interventions has been applied in the management of TRAP; however, because of the rarity of this condition and the heterogeneity of its presentation, no single technique has been shown to be unequivocally optimal. In our experience, fetoscopic laser coagulation of the placental vascular anastomoses or the umbilical cord of the acardiac twin, with the possibility of applying bipolar forceps as an additional minimally invasive surgical technique, offers an effective treatment option in the management of the TRAP sequence; this treatment has a survival rate of 80%, and 67% of pregnancies with surviving pump twins go beyond 36 weeks of gestation without further complications. PMID- 17851149 TI - Comparison of breaking forces of the linear, W and Z plasty incisions. PMID- 17851150 TI - Ring chromosome 20 syndrome without deletions of the subtelomeric and CHRNA4- KCNQ2 genes loci. AB - Ring chromosome 20 (r(20)) syndrome is a rare disease characterized by refractory epilepsy, moderate mental retardation and particular electroencephalographic disorder with non-convulsive status epilepticus. Here, we report a new case of r(20) syndrome in a 12 year old female who presented minimal dysmorphism, generalised tonic-clonic and absence seizures refractory to medical therapy and behavioural troubles. Among 20 cytogenetically analysed cells, 14 (70%) exhibited a 46,XX,r(20)(p13q13.3) karyotype and 6 (30%) showed a normal 46,XX caryotype. Interphasic FISH using centromeric probe of chromosome 20 detects the presence of a chromosome 20 monosomy in 7% and a duplicated ring chromosome 20 in 8% of studied cells. Metaphase FISH using chromosome 20 telomeric probes and specific probes of CHRNA4 and KCNQ2 genes detects the absence of any deletion in the ring chromosome 20. Clinical symptoms of r(20) syndrome are attributed to telomeric partial monosomy generated by ring chromosome and causing an haploinsufficiency of two epilepsy genes CHRNA4 and KCNQ2. However, our patient presents the typical epilepsy disorder but no detectable deletion in the ring chromosome 20. We speculate that clinical features of ring chromosome 20 syndrome are caused by low mosaicism of chromosome 20 monosomy caused by the loss of the ring chromosome 20. PMID- 17851151 TI - Area summation in human vision at and above detection threshold. AB - The initial image-processing stages of visual cortex are well suited to a local (patchwise) analysis of the viewed scene. But the world's structures extend over space as textures and surfaces, suggesting the need for spatial integration. Most models of contrast vision fall shy of this process because (i) the weak area summation at detection threshold is attributed to probability summation (PS) and (ii) there is little or no advantage of area well above threshold. Both of these views are challenged here. First, it is shown that results at threshold are consistent with linear summation of contrast following retinal inhomogeneity, spatial filtering, nonlinear contrast transduction and multiple sources of additive Gaussian noise. We suggest that the suprathreshold loss of the area advantage in previous studies is due to a concomitant increase in suppression from the pedestal. To overcome this confound, a novel stimulus class is designed where: (i) the observer operates on a constant retinal area, (ii) the target area is controlled within this summation field, and (iii) the pedestal is fixed in size. Using this arrangement, substantial summation is found along the entire masking function, including the region of facilitation. Our analysis shows that PS and uncertainty cannot account for the results, and that suprathreshold summation of contrast extends over at least seven target cycles of grating. PMID- 17851152 TI - Probing the localized-to-delocalized transition. AB - Detailed understanding of the transition between localized and delocalized behaviour in mixed valence compounds has been elusive as evidenced by many interpretations of the Creutz-Taube ion, [(NH3)5Ru(pz)Ru(NH3)5]5+. In a review in 2001, experimental protocols and a systematic model to probe this region were proposed and applied to examples in the literature. The model included: (i) multiple orbital interactions in ligand-bridged transition metal complexes, (ii) inclusion of spin-orbit coupling which, for dpi5-dpi6 complexes, leads to five low-energy bands, two from interconfigurational (dpi-->dpi) transitions at the dpi5 site and three from intervalence transfer transitions, (iii) differences in time scale between coupled vibrations and solvent modes which can result in solvent averaging with continued electronic asymmetry defining 'class II-III', an addition to the Robin-Day classification scheme, and (iv) delineation of coupled vibrations into barrier vibrations and 'spectator' vibrations. The latter provide direct insight into localization or delocalization and time scales for electron transfer. In this paper, the earlier model is applied to a series of mixed valence molecules. PMID- 17851153 TI - Anaesthesia for CEA-Regional or General. PMID- 17851154 TI - Gene therapy in the management of cardiovascular diseases. AB - Gene therapy is about to create a revolution in the available methods to limit and correct many of the common disease processes involving the heart. Since the human genome was published in draft form a year ago there has been an explosion of scientific activity to translate the DNA code into a language which we can understand in terms of molecular biology and function. The technology is now readily available to test for small variations in the DNA code (Single Nucleotide Ploymorphisms or SNPs) which can explain individual susceptibility to hypertension, hyperlipidaemia, thrombosis, inflammatory response, infection, multiple organ failure and countless other common complications of cardiac surgery. PMID- 17851155 TI - Carotid endarterectomy under regional analgesia:a retrospective study (1988 1999). AB - The procedure of carotid endarterectomy is more or less standardized. Controversies persist on many technical issues, one of which is general versus regional anaesthesia. We retrospectively evaluated the influence of regional analgesia on perioperative complications, the hospital stay and the perioperative mortality after carotid endarterectomy in 53 patients. All the patients in the study received deep cervical block regional anaesthesia (Winne's technique) for carotid endarterectomy. Indications for surgery included transient ischaemic haemodynamically significant stenosis. Shunt was used in 7 cases (13.2%). General anaesthesia was supplemented in 2 patients (3.8%). There was no perioperative mortality. Permanent non-fatal neurologic deficit occurred in 1 patient (1.9%) and temporary neurologic Deficit occurred in 1 patient (1.9%). The mean ICU stay was 1.85 (+/-0.82) days and the hospital stay was 5.2 (+/-1.14) days. On the basis of our data we believe that under regional anaesthesia carotid endarterectomy can be performed with acceptable complications and that regional anaesthetic technique is safe and well tolerated by the patients. PMID- 17851156 TI - Post-operative Pain Relief by PCA v/s Oral Tramadol in Cardiac Surgery. AB - Pain relief is pivotal in anaesthesiology practice. Postoperative cardiac surgical patients need good pain relief for haemodynamic stability, early extubation, cooperation for chest physiotherapy and prevention of pulmonary dysfunction; thus reducing and prevention of pulmonary the ICU stay. This prospective study was carried out is 50 patients undergoing coronary artery bypass graft (CABG) to assess postoperative pain relief with patient controlled analgesia (PCA) tramadol as compared to oral tramadol after extubation. Visual analogue scale for pain relief, tidal volumes by spirometry, arterial blood gas, and oxygen saturations were the parameters used to compare both groups. [Study group(Group I) -receiving PCA tramaol and Control group (Group II) -receiving oral tramadol]. PCA tramadol was found to be very effective after 4 hrs post operatively. PMID- 17851157 TI - A comparison of the inotropic effects of milrinone and piroximone. AB - Patients with low cardiac output syndrome often have a reduced sensitivity to inotropes acting via the beta-adrenergic receptors. In this situation, drugs such as milrinone and piroximone may have a therapeutic advantage. Strips of human right atrial appendage were used to examine the inotropic actions of phosphodiesterase (PDE) inhibitors, measured as an increase in isometric tension in response to electrical stimulation at a frequency of 1 Hz. Cumulative concentration response curves were established for piroximone (an imidazalone derivative) and Milrinone (a bipyridine derivative.) Concentration response curves were then recorded to adrenaline in the presence or absence of the EC50 of each PDE inhibitor. The results indicate that these drugs, under the conditions employed in these experiments, have a significant inotropic effect when used alone. They also have a significant additive and potentiating effect when used in combination with adrenaline. Milrinone produced a significantly greater maximum tension as a percentage of basal tension, and has a lower EC50 than Piroximone. PMID- 17851158 TI - Changes in transfusion therapy guided by thromboelastograph in cardiac surgery. AB - This study was conducted to determine the use of thromboelastograph in predicting excessive postoperative bleeding, detecting coagulopathy related bleeding, reducing usage of blood and blood products and aiding reexploration decisions. One hundred fifty patients undergoing coronary artery bypass graft surgery under cardiopulmonary bypass were randomized and studied prospectively in two equal groups. In the study group, celite activated heparinase pretreated blood samples, 30 minutes after protamine administration were subjected to thromboelastographic analysis and blood and blood component therapy was administered based on thromboelastograph values, if they had significant bleeding. In the control group transfusion therapy was based on routine coagulation tests and clinical judgement of the surgeon. Patients who bled 100ml / hour in the first three hours or 300 ml in the first three hours and 75 ml/hour in the next three hours were considered significant bleeders. Haematocrit at 0,6,12,18,24,30 and 36 hours of shifting to intensive care unit were noted. Accuracy of thromboelastograph in predicting excess postoperative bleeding was found to be 92%. Consumption of whole blood, packed red blood cells and fresh frozen plasma (p values 0.03, 0.05, 0.001 respectively) was significantly less in the study group. There was poor correlation between postoperative bleeding and platelet count but those who did not bleed had a significantly higher platelet count as compared to those who did. Except at 30 hours, haematocrit was significantly higher in the study group up to 36 hours. Thromboelastograph is a useful diagnostic tool to detect coagulopathies following cardiopulmonary bypass. It helps in instituting appropriate blood and blood component therapy thereby avoiding unnecessary transfusion and associated risks. Accurate detection of coagulopathy is possible with heparinase pretreatment of the blood sample. PMID- 17851159 TI - Combination of autologous Transfusion and Retrograde Autologous Priming Decreases Blood Requirements. AB - In a prospective study, 60 patients posted for coronary artery bypass graft (CABG) surgery on cardiopulmonary bypass (CPB) were assigned to 2 groups of 30 each. (group A =combination of acute normovolaemic haemodilution (ANH) and retrograde autologous priming (RAP), group B=control). The aim was to investigate whether retrograde autologous priming reduces haemoditution as compared to control cases. Patients who had a history of previous cardiac surgery and patients with severe left ventricular dysfunction, were excluded. Group A patients were subjected to pre-CPB intraoperative autologous blood collection prior to heparin administration. Heparin was given (300IU/Kg) and the aorta was cannulated. In addition, prior to bypass, if the patients had a systolic BP>100 mm Hg, 300cc of their blood was withdrawn in a retrograde manner via aortic cannula into the CPB circuit up to the arterial filter, while the 'displaced' asanguinous prime was diverted into a transfer bag. The total bank blood (whole blood) used intra-op was 26 units in the study group [mean 0.86 unit per patient] versus 52 units in the control group (mean 1.73 units per patient) (P<0.001). Blood components and products were not used in this study. The average fall in haematocrit (Hct) on CPB was 27.03% in the study group versus 39.5% in the control group (P < 0.001). Thus retrograde autologous griming in combination with autologus transfusion significantly reduces the need for bank blood. PMID- 17851160 TI - Critical stenosis of bicarotid trunk and left subclavian artery with severe coronary artery disease - a management dilemma. AB - A 48 yr. old patient suffering from bicarotid trunk and left subclavian artery stenosis with severe coronary artery disease was managed successfully by angioplasty and stenting of the bicarotid trunk and subclavian artery. This was followed by coronary artery bypass grafting after one month. He was free of angina and cerebrovascular symptoms at one and a half year follow up. PMID- 17851161 TI - Shone's Anomaly - A Case Report. AB - Shone's anomaly, a rare congenital cardiac malformation consists of multiple levels of left heart obstruction - supravalvar mitral ring, parachute mitral value, subaortic stenosis and coarctation of the aorta. Although they present with a wide spectrum of major anatomical and haemodynamic abnormalities, a satisfactory outcome is possible for most patients. The operative mortality and outcome is affected by the severity of mitral value disease and the need for multiple operative procedures. We report one such case with this anomaly who presented to us in the third decade. He underwent a two - stage procedure in a single sitting successfully. PMID- 17851162 TI - An unusual way to use an endobronchial blocker. AB - The techniques for lung isolation in infants are, endobronchial intubation and bronchical blockade with Fogarty catheter or a univent tube. Unlike endobronchial intubation, bronchial blockade has the advantage that lung can be segregated at will. Endobronchial blocker is usually placed as a planned procedure just after induction of anaesthesia either under vision with the help of a fibreoptic bronchoscope or alternatively a rigid bronchoscope is used to position it in either bronchus and later the trachea. We report here a rather unusual and desperate way of using a Fogarty catheter halfway through the surgery due to unforeseen bleeding during thoracotomy. The pros and cons of attempting selective segregation and regional ventilation of lung under these circumstances is discussed. PMID- 17851163 TI - Successful post-cardiopulmonary resuscitation urokinase therapy for massive perioperative pulmonary embolism - a case report. AB - We report a case of hip arthroplasty done under epidural and general anaesthesia. The patient had two episodes of acute massive pulmonary embolism perioperatively. He received cardiopulmonary resuscitation for the cardiovascular collapse that ensued and was administered a single dose of urokinase inspite of having relative (major) contraindications to the same. PMID- 17851164 TI - Viscoelasticity of human whole saliva collected after acid and mechanical stimulation. AB - The rheology of saliva is highly important due to its influence on oral health and physiochemical processes within the oral environment. While the rheology of human whole saliva (HWS) is considered important for its functionality, its measurement is often performed erroneously and/or limited to the viscosity at a single shear rate. To ensure accurate rheological measurements, it is necessary to test HWS immediately after expectoration and to apply a thin layer of surfactant solution around the rim of the rheometer plates so that protein adsorption is minimized at the air-liquid interface. It is shown for the first time that the viscosity and viscoelasticity of HWS depends greatly upon the method of stimulation. Mechanical action stimulates slightly shear-thinning and relatively inelastic saliva, while acidic solutions (e.g. 0.25% citric acid) stimulate secretion of saliva that is highly elastic and shear-thinning. However, both acidic solutions and mechanical action stimulate similar volumes of saliva. For acid-stimulated saliva, the ratio of the primary normal stress difference to the shear stress is of order 100 and the viscosity at high shear rates is only marginally above that of water. This extremely high stress ratio for such a low viscosity fluid indicates that saliva's elastic properties dominate its flow behavior and may assist in facilitating lubrication within the oral cavity. It is anticipated that the variation in saliva rheology arises because the individual glands secrete saliva of different rheology, with the proportion of saliva secreted from each gland depending on the method of stimulation. The steady-shear rheology and linear viscoelasticity of HWS are described reasonably well using a FENE-P constitutive model and a 3-mode Maxwell model respectively. These models indicate that there are several long relaxation modes within saliva, possibly arising from the presence of large flexible macromolecules such as mucin glycoproteins. PMID- 17851165 TI - Investigation of platelet margination phenomena at elevated shear stress. AB - Thrombosis is a common complication following the surgical implantation of blood contacting artificial organs. Platelet transport, which is an important process of thrombosis and strongly modulated by flow dynamics, has not been investigated under the shear stress level associated with these devices, which may range from tens to several hundred Pascal.The current research investigated platelet transport within blood under supra-physiological shear stress conditions through a micro flow visualization approach. Images of platelet-sized fluorescent particles in the blood flow were recorded within microchannels (2 cm x 100 microm x 100 microm). The results successfully demonstrated the occurrence of platelet sized particle margination under shear stresses up to 193 Pa, revealing a platelet near-wall excess up to 8.7 near the wall (within 15 microm) at the highest shear stress. The concentration of red blood cells was found to influence the stream-wise development of platelet margination which was clearly observed in the 20% Ht sample but not the 40% Ht sample. Shear stress had a less dramatic effect on the margination phenomenon than did hematocrit. The results imply that cell-cell collision is an important factor for platelet transport under supra physiologic shear stress conditions. It is anticipated that these results will contribute to the future design and optimization of artificial organs. PMID- 17851166 TI - Participation of caspase-3-like protease in oxidation-induced impairment of erythrocyte membrane properties. AB - Erythrocytes are very susceptible to oxidative stress, having a high content of intracellular oxygen and hemoglobin. In the present study, exposure to oxidative stress resulted in a significant impairment of erythrocyte membrane functions, such as deformability and anion exchange. Band 3 protein, also known as anion exchanger-1, plays an important role in these two functions. We show that oxidative stress activated caspase-3 inside the erythrocytes, which resulted in band 3 protein cleavage. Interestingly, inhibition of the caspase-3 with its specific inhibitor not only suppressed the digestion of band 3 protein, but also blunted the functional damage to erythrocytes, such as deformability and anion exchange, without changing the level of peroxidation of membrane lipids. These results provide experimental evidence that activation of caspase-3 plays an important role in the oxidative stress-induced impairment of membrane functions of erythrocytes. PMID- 17851167 TI - Hydrodynamic interaction between erythrocytes and leukocytes affects rheology of blood in microvessels. AB - Hydrodynamic interaction between erythrocytes (RBC) and leukocytes (WBC) in a microvessel of size 20-40 micron, typical of a postcapillary venule, is studied using a two-dimensional computational model. The model is based on immersed boundary method, and it takes into consideration the particulate nature of blood by explicitly modeling individual blood cell, and cell deformation. Due to their highly flexible nature, RBC drift away from the wall and toward the center of a vessel creating a cell-free layer. It is shown here that the lateral motion of RBC is strongly affected in presence of a WBC, and is dependent on whether the WBC is non-adherent or firmly adhered. When the WBC is non-adherent, some RBC, depending on their initial radial locations and vessel size, may be deflected closer toward the wall, resulting in a decrease in the cell-free layer. The apparent viscosity of the whole blood containing both RBC and WBC is computed, and shown to be much higher than that containing RBC only. The increased viscosity cannot be accounted for by the contribution due to WBC only. This observation is in agreement with a previous in vivo measurement. Here we show that the additional flow resistance is due to the decrease in the cell-free layer resulting from the WBC-RBC interaction. It can be accounted for by a two-layer model of blood when the reduced values of the cell-free layer thickness are used. When the WBC is firmly adhered, RBC easily move away from the wall, and the cell free layer is not significantly changed. In such cases, the major contribution to whole blood viscosity comes from the WBC alone. The hydrodynamic interaction between WBC and RBC, though it exists, does not contribute significantly when WBC are adhered. PMID- 17851168 TI - Structural and chemical changes in ultra-high-molecular-weight polyethylene due to gamma radiation-induced crosslinking and annealing in air. AB - Ultra-High-Molecular-Weight-Polyethylene (UHMWPE) is the material of choice for one of the articulating surfaces in many total joint replacements, notably hip and knee prostheses. The various methods used by the orthopaedic biomaterials industry to sterilize and anneal UHMWPE components, and the resulting oxidation and crosslinking, affect the mechanical wear resistance properties in ways still unknown at the microscopic and molecular levels. Transmission electron microscopy and chemical pyrolysis were used to quantify crosslinking induced by gamma irradiation and annealing in air. Changes in lamellar stacking and the amount of crosslinking suggest two types of crosslinking: relatively unstable crosslinks in the amorphous region initially resulting from gamma irradiation which are later replaced by more thermally stable crosslinks resulting from rearrangements at the annealing temperature. Lamellar mobility, the ability of crystalline lamellae to flow in the material, is enhanced during the transition from one type of bond to the other, and this appears to optimize near eight hours of annealing time. Results from decomposition and percent crystallinity measurements provide further support for this theory. PMID- 17851169 TI - Effect of chondrocyte passage number on histological aspects of tissue-engineered cartilage. AB - Transplantation of cultured chondrocytes can regenerate cartilage tissue in cartilage defects. This method requires serial cell passages to expand chondrocytes to a large number of cells for transplantation. However, as chondrocytes are expanded in number in monolayer culture, the cells gradually lose their differentiated phenotype and may not form cartilage tissue. This study investigated whether chondrocytes cultured through various passages maintain their potential to reexpress a chondrogenic phenotype in three-dimensional scaffolds and form cartilage tissue in vitro and in vivo. The growth rate, viability, synthesis of collagen type I and II, and apoptotic activity of chondrocytes with passage number of 1, 2 and 5 were compared during in vitro culture. As the passage number increased, the cell growth rate and viability decreased and apoptotic cell increased. Passage 2 chondrocytes exhibited a high expression of collagen type II and a low expression of collagen type I. In contrast, passage 5 chondrocytes exhibited a low expression of collagen type II and a high expression of collagen type I, indicating chondrocyte dedifferentiation. To examine the ability of chondrocytes to regenerate cartilage tissues in vitro and in vivo, chondrocytes were expanded in vitro to passage number of 1 or 5, seeded onto biodegradable polymer scaffolds, and maintained in vitro or implanted into subcutaneous spaces of athymic mice for 1 month. Histological and immunohistochemical analyses of cartilage tissues engineered in vitro and in vivo with passage 1 chondrocytes showed mature and well-formed cartilage and the presence of highly sulfated glycosaminoglycans and type II collagen, a collagen type produced by differentiated chondrocytes. In contrast, tissues engineered in vitro and in vivo with passage 5 chondrocytes did not have chondrocyte morphology or cartilage-specific extracellular matrices (i.e., glycosaminoglycans and type II collagen). The results of this study show that chondrocyte passage number is an important factor affecting the quality of cartilage tissue-engineered with the chondrocytes, and that chondrocytes. PMID- 17851170 TI - Hollow calcium phosphate microcarriers for bone regeneration: in vitro osteoproduction and ex vivo mechanical assessment. AB - Synthetic grafting materials, such as calcium phosphates (hydroxyapatite, HA; tricalcium phosphate, TCP), polymers, or composites thereof, can be used as osteoconductive scaffolds and delivery vehicles for osteoinductive growth factors. Carrier materials must be engineered to deliver these factors in a controlled fashion at a rate and dose consistent with the biological need and responsiveness of the system to optimize bone formation and ingrowth. They should also simultaneously provide mechanical support and slowly resorb as new bone is formed. This investigation assessed the elution characteristics of BMP-7 (OP-1) from hollow calcium phosphate spheres of varying chemical composition (HA/beta TCP) and porosity (dense/porous). The pharmacokinetics indicated a bimodal trend of protein release with protein elution peaking between fifteen and thirty minutes in solution (bolus release) and continuing through the eight-week time point (sustained release). Eluted OP-1 bioactivity was characterized over a three week period using mesenchymal stem cell (MSC) cultures and included assessment of the protein's differential, proliferative, and calcified nodule forming abilities. Alkaline phosphatase enzyme (ALP) activity in MSCs peaked between 12 and 16 days post-OP-1 exposure. Elutant from the HA dense treatment group induced the highest degree of ALP expression while elutant from the beta-TCP treatment groups induced the formation of significantly higher numbers of calcified nodules in culture. The aggregate modulus of a clinically relevant 2 cc dose of carriers was quantified using custom designed testing fixtures to investigate the effects of carrier size, porosity, chemical composition, and the presence of a central hole on mechanical integrity. Significant increases in moduli were noted for carrier size and chemical composition (HA>beta-TCP). These preliminary in vitro and ex vivo results indicate the clinical potential of the hollow calcium phosphate carriers as successful load-bearing delivery vehicles for OP-1. PMID- 17851171 TI - RF-magnetron sputtering technique for producing hydroxyapatite coating film on various substrates. AB - A sputtering technique is an effective method for surface modification of materials, but there are many complex process parameters to influence on the physical and chemical properties of the sputtered coating films. In this paper the process parameters were investigated when the hydroxyapatite (HA) was coated onto various substrates including titanium (Ti), alumina ceramic (Al(2)O(3)) and stainless steel (SUS) plates under various sputtering conditions, target type, Ar gas pressure, and discharge power. The deposition rate of HA was much higher in a solid plate target than in a powder lump target owing to the difference of apparent density 75%, 18%, respectively. Ar gas pressure little influenced on the deposition rate. The HA coating thickness increased in proportion with discharge power. After hydrothermal treatment the thickness of HA slightly decreased, on the other hands Ca/P ratio slightly raised. The surface of the HA coating was smooth, homogeneous and dense. PMID- 17851172 TI - Vertebral fractures fixation with composite patch fibre reinforced adhesives. AB - PURPOSE: The aim is to investigate fixation of cervical vertebral fractures by patching it with a composite laminate of adhesive and fibres, in comparison with use of only adhesives. MATERIAL AND METHODS: The composite fixation was tested on bonded roe deer vertebrae. 25 specimens were sawed in two halves, creating a generic fracture, and thereafter bonded. The adhesives used were a dental system, Scotchbond XT, and a cyanoacrylate, M-bond 200. The fibres used were unidirectional carbon fibres and randomly distributed E-glass fibres. The composites were applied as a 7 mm wide patch circumferential along the induced fracture. Reference specimens for comparison were also made. The ultimate tensile strength was tested in an Instron 5567. The failure site was examined with a microscope. Strain vectors were tracked using Digital Speckle Analysis. RESULTS: Scotchbond XT + E-glass fibres gave best results, with a tensile strength of 3.5 N/mm circumferential length (24.3% of reference). All composites had lower stiffness than cortical bone. The dental adhesive fibre composites gave better results than the cyanoacrylate fibre composites. In all cases fibre reinforced adhesive composite gave better results than adhesive without fibre reinforcement. CONCLUSION: Fibre-adhesive composite is a promising technique for fixating cervical vertebral fractures. PMID- 17851173 TI - Effects of chitosan addition to self-setting bone cement. AB - The Cementek is a self-setting bone cement composed of a solid phase and a liquid phase. After mixing these two phases, it sets in situ to form an hydroxyapatite (HAp) as the only end product. It is difficult to introduce a new component into this cement without modifying the final product and its mechanical properties. In order to improve the mechanical properties of the Cementek, a natural polymer (chitosan) was added in the initial formulation. Two types of chitosan were added into the Cementek, at various concentration, in either the liquid or the solid phase. The effects of chitosan addition on the properties of the self-setting bone cement are examined. The different composites were characterized by the determination of the setting time, the chemical transformation by X-ray diffraction and mechanical tests. The chemical transformations were not affected by the addition of chitosan neither in the liquid nor in the solid phase. The maturation towards HAp appeared to be complete for all the composites. The setting time was decreased by the addition of chitosan in the solid phase. However the setting time value of each composite remained compatible with a practical use in situ. This study shows that the maturation mode of the samples directly affects the mechanical properties of the obtained composites. The sterilization of the cement with chitosan has been studied. PMID- 17851174 TI - In vitro study on influence of a discrete nano-hydroxyapatite on leukemia P388 cell behavior. AB - Influence of a discrete nano-hydroxyapatite crystal (nano-HAp) on lymphatic leukemia P388 cell behavior was investigated by an in vitro technique using an MTT test and FITC analysis. The discrete nano-HAp was prepared by decanting upside clear layer of the nano-HAp suspension which was synthesized by a wet method using calcium hydroxide suspension and phosphoric acid solutions. The nano HAp was identified as hydroxyapatite by the X-ray powder diffraction pattern and an infrared spectroscopy. The nano-HAp with concentrations of 8-40 microg/ml was dispersed into PRMI 1640 media with leukemia cells derived from BALB/C mice. The survival ratio of the cells decreased with the amounts of the nano-HAp increasing. Apoptosis rates of leukemia P388 cells on co-culturing with the nano HAp of 35 microg/ml for 24, 48 h were 14.5% and 45.8%, respectively, and higher than those of 10.4% and 34% in controls. The G0/G1 peak values in leukemia P388 cell cycle were declined to reduce and the S peak values increased with extension time of co-culture. These results proved that the discrete nano-HAp can cause apoptosis of the leukemia P388 cells, and selectively act on G1 phase and arrest the G1 phase in cell cycle of the leukemia P388. PMID- 17851175 TI - More than just sunshine with implantation of resorbable (p(DLLA-epsilon-CL)) biomaterials. PMID- 17851176 TI - Cholesterol secoaldehyde, an ozonation product of cholesterol, induces amyloid aggregation and apoptosis in murine GT1-7 hypothalamic neurons. AB - Aldehydic products from ozonation of cholesterol and peroxidation of phospholipids have been shown to accelerate aggregation of amyloid-beta (Abeta) in vitro. Here, we show that 3beta-hydroxy-5-oxo-5,6-secocholestan-6-al (ChSeco), an ozonation product of cholesterol, induces Abeta aggregation, generation of reactive oxygen species (ROS), and cytotoxicity in murine GT1-7 hypothalamic neurons. The formation of Abeta aggregates in situ was dose-dependent at ChSeco concentrations ranging from 1 to 20 microM. The increase in insoluble Abeta aggregates at increasing concentrations of ChSeco was accompanied by a decrease in soluble Abeta as evidenced by Western blot analysis. The formation of ROS in neuronal cells was found to be dose- and time-dependent with the magnitude being higher at 20 microM compared to 10 microM ChSeco or untreated controls. The increase in ROS was associated with depletion of GSH. The cytotoxicity induced by ChSeco involved changes in phosphatidylserine translocation, DNA fragmentation, and caspase 3/7 activity that are characteristic of apoptosis. Pretreatment of neuronal cells with Trolox, a water-soluble analog of alpha-tocopherol offered partial, but significant protection against ChSeco-induced cell death, whereas, N acetyl-L-cysteine (NAC) completely prevented the cytotoxic effects of ChSeco. NAC and Trolox were without any effects on ChSeco-induced Abeta aggregation. Fibrillogenesis inhibitors, which inhibited Abeta aggregation, did not inhibit cell death induced by ChSeco, implying that ROS generation, and not Abeta aggregation, plays a major role in the observed cytotoxicity. However, since Alzheimer's and other neurodegenerative diseases are slow and progressive, the formation of Abeta aggregates in vivo by ChSeco may have long-term pathological consequences. PMID- 17851177 TI - gamma-Secretase is differentially modulated by alterations of homocysteine cycle in neuroblastoma and glioblastoma cells. AB - Multiple aspects of homocysteine metabolism were studied to understand the mechanism responsible for hyperhomocysteinemia toxicity in Alzheimer disease. Besides oxidative stress and vascular damage, homocysteine has also a great importance in regulating DNA methylation through S-adenosylmethionine, the main methyl donor in eukaryotes. Alterations of S-adenosylmethionine and methylation were evidenced in Alzheimer disease and in elderly. In order to clarify whether DNA methylation can provide the basis for amyloid-beta overproduction, we used human SK-N-BE neuroblastoma and A172 glioblastoma cell lines. We tested the effects of folate, B12 and B6 deprivation and S-adenosylmethionine addition on methylation metabolism. Our results indicate that homocysteine accumulation induced through vitamin B deprivation could impair the "Methylation Potential" with consequent presenilin 1, BACE and amyloid-beta upregulation. Moreover, we found that homocysteine alterations had an effect on neuroblastoma but not on glioblastoma cells; this suggests a possible differential role of the two cell types in Alzheimer disease. PMID- 17851178 TI - Substituted organosiloxanes as potential therapeutics for treatment and prevention of neurodegenerative diseases. AB - Extensive testing of hydrolysates of commercially available organosilanes has identified a number of bifunctional organosiloxane compounds that show potential as therapeutics for treatment of diseases characterized by amyloid deposition such as Alzheimer's disease (AD). All of these compounds protect from and/or reverse the metal-induced aggregation of amyloid Abeta(1-42) peptide in dynamic light scattering (DLS) assays in trifluoroethanol (TFE) solutions, protect from and/or reverse the metal-induced loss of alpha-helical structure in TFE solutions of amyloid Abeta(1-42) as measured by circular dichroism (CD), and are able to cross blood-brain barrier models at rates above background using Caco-2 and MDCK cell permeation assays. Based on these studies, we conclude that members of this class of bifunctional organosiloxanes are promising candidates for testing in treatment and/or prevention of AD and other diseases characterized by amyloid deposition. PMID- 17851179 TI - Organosilicon therapy in Alzheimer's disease? PMID- 17851181 TI - IL-8 induces expression of matrix metalloproteinases, cell cycle and pro apoptotic proteins, and cell death in cultured neurons. AB - Neuronal cell loss is a critical feature of age-related neurodegenerative diseases such as Alzheimer's disease (AD). In the AD brain, a marked increase in pro-inflammatory cytokines and chemokines, including IL-8, has been documented. The objective of this study was to determine the effect of IL-8 on cell viability and expression of neurotoxic, apoptotic, and cell cycle proteins in cultured neurons. Incubation of cultured neurons with IL-8 for 24 h resulted in neuronal cell death. RT-PCR analysis of primary rat neuronal cultures treated with IL-8 for 24 h showed induction of genes for matrix metalloproteinases (MMP-2 and MMP 9), proinflammatory proteases with neurotoxic properties. Gelatin zymography demonstrated IL-8 induced MMP-2 and MMP-9 activity. Western blot analysis showed that IL-8 also increased levels of the pro-apoptotic protein Bim (Bcl-2 interacting mediator of cell death). In addition, message levels of the cell cycle protein cyclin D1, an early marker for G1/S transition and a protein implicated as a regulator of neuronal apoptosis, were elevated after IL-8 exposure. These results suggest that IL-8 could be an important mediator of neuronal death in AD both via its effects on release of neurotoxins such as MMPs as well as by induction of cell cycle and pro-apoptotic proteins. PMID- 17851182 TI - Alzheimer's disease and smoking: bias in cohort studies. AB - The discrepancy between cohort and case-control studies regarding the association between smoking and Alzheimer's disease (AD) has been attributed to the competing risk of early mortality of smokers. A simulation study was conducted to show that the bias favoring smokers acts also on cohort studies. In the model, individuals {grow older} and have smoking habits according to published year-age-gender specific patterns, with morbidity and mortality according to their demographic and smoking profiles. Those individuals dying of smoking-related causes ("phantoms") remain at risk of AD and of death from other causes. Three scenarios were considered: no association of AD and smoking, increased risk for smokers, and decreased risk for smokers. For each simulation of a cohort study, two incidence density ratios (IDR) were computed: one including the phantoms that developed AD (thus ignoring smoking-related deaths) and another excluding them (thus mimicking real-life studies). For all scenarios, the simulations show that smoking-related death creates a bias, resulting in smokers having an understated risk of AD compared to non-smokers. The speculation that the conflicting results of case-control and cohort studies are solely due to the increased mortality in smokers thus appears unjustified. Other factors must also be considered to explain the discrepancy in results. PMID- 17851183 TI - Detecting cognitive impairment in primary care: performance assessment of three screening instruments. AB - Early detection of Alzheimer's disease and related disorders (ADRD) is important, especially in primary care settings. We compared performances of two common screening tests, the Mini-Mental State Exam (MMSE) and Clock Drawing Test (CDT), with that of the MCI Screen ({MCIS}) in 254 patients over 65. None had previous diagnosis of ADRD, and 81% were asymptomatic by Functional Assessment Staging Test ({FAST}) (FAST=1). 215 patients completed all screening tests - 141 had >or= 1 abnormal result, 121/141 completed standardized diagnostic assessment, and the remaining 74/215 (34%) screened entirely normally and weren't further evaluated. Potential bias due to unevaluated cases was statistically adjusted. Among diagnosed cases: AD=43%, cerebrovascular disease=36%, other causes=21%. Bias adjusted MCI prevalence for FAST stages 1 and 1-3 were 13.9-20.3% and 23.0-28.3%. Bias-adjusted results for the CDT, MMSE and MCIS were: clinical diagnosis validity (kappa statistic)={-0.02 (p=0.61), 0.06 (p=0.23), 0.92 (p< 0.0001)}; sensitivity={59%, 71%, 94%}; specificity={39%, 36%, 97%}; overall accuracy={54%, 62%, 96%}; positive predictive value={16%, 17%, 86%}; and negative predictive value={83%, 87%, 96%}. The MMSE and CDT were not valid for early detection, while the MCIS had high validity and accuracy in the primary care cohort. PMID- 17851184 TI - Height and Alzheimer's disease: findings from a case-control study. AB - The purpose of this study is to examine the relationship of height, Apolipoprotein E genotype (APOE) and Alzheimer's disease (AD). Using a case control design, subjects were recruited from the research registry of the University Memory and Aging Center of Case Western Reserve University and University Hospitals of Cleveland. On entry to the study, height was measured on 239 probable or possible AD patients and 341 healthy controls living in northeast Ohio. Risk of AD was modeled as a function of quartile of height, APOE genotype, years of education and year of birth. Analyses were stratified by gender. For men, cases were more likely to be shorter when compared to controls (p=0.001). There was only a small difference in mean height between AD cases and controls among women (p=0.05). For men, height in the highest quartile [>179.7 cm (70.75 in)] had a 59% lower risk of developing AD that in the lowest quartile [< 169.5 cm (66.75 in)], controlling for year of birth, and education (p=0.03). For women without an APOE epsilon4 allele, increasing height was associated with lower risk for AD (OR=0.88; p=0.01) but no significant association was found for women with at least one epsilon4 allele (OR=1.03; p=0.56). PMID- 17851185 TI - AICD and its adaptors - in search of new players. AB - In view of the emerging evidence that amyloid-beta load in the brain and neuronal deficits are possibly independent events and the increasing importance of downstream molecular cascades in Alzheimer's Disease (AD) pathogenesis, the role of Amyloid Intracellular C-terminal Domain (AICD) is evaluated. This C-terminal fragment of Amyloid-beta protein precursor (AbetaPP) is cytotoxic and is a major component of AD brain. Different portions of AICD bind to different 'adaptors' and are seen to take part in various cellular events including AbetaPP processing and trafficking, apoptosis, neuronal growth and regulation of gene transcription. Phosphorylation also plays an important role in terms of choice of binding partners. The review emphasizes the dynamics of the network created by AICD interactions and points to possible alternative routes of AD like neurodegeneration. PMID- 17851186 TI - Environmental enrichment delays the onset of memory deficits and reduces neuropathological hallmarks in a mouse model of Alzheimer-like neurodegeneration. AB - Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive memory deficits and cognitive decline. We explored the possibility that Environmental Enrichment (EE) may reduce the disease progression in a comprehensive mouse model for AD like neurodegeneration, the AD11 mice. AD11 mice, which express anti nerve growth factor (NGF) antibodies, develop an age dependent neurodegeneration which encompasses all hallmarks of human AD. We have tested the efficacy of EE starting from 2 months of age, that is before the onset of behavioural deficits in AD11 mice. At 7 months of age, visual recognition memory was tested with the Object Recognition Test (ORT), spatial memory with the Morris Water Maze (MWM) and the presence of AD pathological hallmarks (Abeta clusters, presence of hyperphosphorylated tau and cholinergic deficit) was assessed immunohistochemically. We found that in AD11 mice exposed to EE from 2 to 7 months of age performance in both memory tests was significantly better than in non EE AD11 mice and indistinguishable from that in wild-type mice of the same age. Exposure to EE from 2 to 7 months significantly reduce the appearance of AD neuropathological hallmarks. A group of AD11 mice was tested also at 12 months of age: we found that 12 months old AD11 mice exposed to EE from 2 to 7 months of age performed significantly better than non EE AD11 mice of the same age and did not differ from 12 months old wt mice. Thus, EE is able to prevent the onset of memory deficits up to at least 12 months of age and to restrain the progression of neurodegeneration in a mouse model of AD. PMID- 17851187 TI - A rabbit model of Alzheimer's disease: valid at neuropathological, cognitive, and therapeutic levels. AB - Supplementing a rabbit's diet with 2% cholesterol alone or with a trace amount of copper created neuropathological changes that resembled those seen in Alzheimer's disease (AD). AD model rabbits were impaired in eyeblink classical conditioning; a form of learning severely impaired in AD. Our aim was to replicate AD rabbit model neuropathology, test eyeblink conditioning in this model, and determine if galantamine (Razadyne) would ameliorate impaired conditioning. In Experiment 1 rabbit chow with 2% cholesterol and drinking water with 0.12 mg/liter copper sulfate were administered for 10 weeks. Control rabbits received normal food and water. Rabbit brains were probed for neuropathology. AD model rabbits had significant neuronal loss in frontal cortex, hippocampus and cerebellum. Changes in neurons in the hippocampus were consistent with neurofibrillary degeneration and cytoplasmic immunoreactivity for amyloid-beta and tau. In Experiment 2 AD model rabbits were injected daily with vehicle or 3.0 mg/kg galantamine and tested on 750 ms trace and delay eyeblink conditioning. Galantamine improved eyeblink conditioning significantly over vehicle. The AD rabbit model has validity from neuropathological to cognitive levels and offers a promising addition to the available animal models of AD. Galantamine ameliorated impaired eyeblink conditioning, extending the validity of the AD rabbit model to treatment modalities. PMID- 17851188 TI - Kalirin is under-expressed in Alzheimer's disease hippocampus. AB - To identify genes aberrantly expressed in the brain of individuals with Alzheimer's Disease (AD), we analyzed RNA extracts from the hippocampus and cerebellum from 19 AD patients and 15 age- and sex-matched control subjects. Our analysis identified a number of genes that were over-expressed or under-expressed specifically in AD hippocampus. Among these genes, kalirin was the most consistently under-expressed in AD hippocampus, which was verified by semi quantitative RT-PCR and real time PCR. Kalirin is predominantly expressed in the brain, particularly in the hippocampus, and plays crucial roles in neuronal stability and growth. Our observation is the first to relate kalirin to AD and a human disease. In addition to kalirin, the genes for voltage-gated Ca++ channel gamma subunit 3 and visinin-like protein 1 (a Ca++ sensor protein) were under expressed, whereas inositol 1,4,5-triphosphate 3-kinase B was over-expressed in AD hippocampus. Collectively, these differential expressions could severely impair calcium homeostasis. Remarkably, these aberrant gene expressions in AD hippocampus were not observed in AD cerebellum. Furthermore, housekeeping genes such as ribosomal protein genes are not affected by AD. These results provide new insights into the biochemistry of AD. PMID- 17851190 TI - Our aging societies: ethical, moral, and policy challenges. AB - The aging of industrialized nations poses grave ethical, moral, and policy challenges for health professionals and our societies. The demand for both acute and long-term health care for the elderly will increasingly strain the economic resources of older persons and our nations. These pressures generate a number of difficult issues for our aging societies. Three of the most important issues are: (1) How aggressive should curative medical treatment be for severely demented patients?; (2) How should the financial burden of long-term care be distributed between the public and private sectors?; (3) Should public policies establish old age-based limits on acute medical care in order to conserve resources? These issues are complex, of great importance, and require substantial reflection and discussion by health care professionals and the public at-large. PMID- 17851191 TI - Brain reserve hypothesis in dementia. AB - The concept of brain reserve refers to the ability to tolerate the age-related changes and the disease related pathology in the brain without developing clear clinical symptoms or signs. A considerable body of biological research has documented that a number of factors including education, work complexity, social network, and leisure activities may contribute to this reserve allowing cognitive function to be maintained in old ages. Epidemiological studies have also related these factors to the development of dementia, suggesting that intellectual challenges experienced across the whole life span may increase the brain reserve and be crucial for the occurrence of dementia symptoms in late life. This paper is a systematic review of the published epidemiological studies on this topic. The availability of numerous epidemiological and biological data investigating the reserve hypothesis in dementia permits some preliminary conclusions. High education, adult-life occupational work complexity, as well as a mentally and socially integrated lifestyle in late life could postpone the onset of clinical dementia and AD. The relevance of physical activity itself remains in debate, as most physical activities include also social and mental stimulation. Leisure activities with all three components--physical, mental and social--seem to have the most beneficial effect. Delaying dementia onset by five years would halve dementia prevalence and substantially decrease the number of dementia cases in the community. PMID- 17851192 TI - Mild cognitive impairment: a systematic review. AB - MCI is a nosological entity proposed as an intermediate state between normal aging and dementia. The syndrome can be divided into two broad subtypes: amnestic MCI (aMCI) characterized by reduced memory, and non-amnestic MCI (naMCI) in which other cognitive functions rather than memory are mostly impaired. aMCI seems to represent an early stage of AD, while the outcomes of the naMCI subtypes appear more heterogeneous--including vascular dementia, frontotemporal dementia or dementia with Lewy bodies--but this aspect is still under debate. MCI in fact represents a condition with multiple sources of heterogeneity, including clinical presentation, etiology, and prognosis. To improve classification and prognosis, there is a need for more sensitive instruments specifically developed for MCI as well as for more reliable methods to determine its progression or improvement. Current clinical criteria for MCI should be updated to include restriction in complex ADL; also the diagnostic and prognostic role of behavioral symptoms and motor dysfunctions should be better defined. A multidisciplinary diagnostic approach including biological and neuroimaging techniques may probably represent the best option to predict the conversion from MCI to dementia. In this review we discuss the most recent aspects related to the epidemiological, clinical, neuropathological, neuroimaging, biochemical and therapeutic aspects of MCI, with specific attention to possible markers of conversion to dementia. PMID- 17851193 TI - One hundred years after the discovery of Alzheimer's disease. A turning point for therapy? AB - Following the introduction of cholinesterase inhibitors in 1986 and a 20-yr long period of successful clinical application in mild, moderate and severe patients, the treatment of AD has turned to modify the course of pathological processes thought to comprise the disease. Several active and passive vaccines are presently under investigation for efficacy, reducing amyloid-beta in the brain of patients with mild-moderately advanced disease. Three large international immunization trials are in progress in US and Europe on mild-moderate AD patients. Among these, the most advanced trial in time is the humanized antibody trial. In addition, drugs aiming to reduce tau phosphorylation (GSK3 inhibitors) are about to enter clinical phases of development. Due to intrinsic difficulties, the developments of gamma-and beta-secretase inhibitors have not yet reached clinical stages. Only one anti-amyloid-aggregation, an aminoglycan compound, and one anti-APO-E approach with rosiglitazone are currently in clinical testing. Stem-cell therapy and gene-replacing therapy remain experimental and far from clinical application. Based on experimental evidence that NGF (nerve growth factor) treatment could provide prolonged protection of the central cholinergic system, i.c.v. infusion of NGF, with genetically modified fibroblasts or gene therapy are under current investigation. NGF treatment could probably double the clinical effect of ChEIs in time. Given the level of scientific and clinical activity it is reasonable to expect that within the next five to ten years a new therapy for AD will, by blocking disease progression, both produce long term stabilization of at least 5 years in patients with AD and prevent or delay emergence in persons at risk for AD. PMID- 17851194 TI - Pharmacological therapy for people with Alzheimer's disease: the balance of clinical effectiveness, ethical issues and social and healthcare costs. AB - The drive for evidence based practice and cost-effective use of pharmacological therapies has advantages, but can also be problematic. These difficulties are particularly challenging in the context of long-term conditions, such as Alzheimer's disease. The complexity of the illness, the variable and complex pattern of service use and the difficulty of conducting long term clinical trials are extremely difficult to factor into a meaningful cost effectiveness model. In Alzheimer's disease, the additional impact on caregivers as well as the person with dementia should be considered. In the current article we give a brief overview of the clinical effectiveness of cholinesterase inhibitors for the treatment of Alzheimer's disease, discuss in detail the NICE appraisal of these treatments in the UK as an example of an attempt at a standardised evaluation of cost-effectiveness and discuss a proposed way forward to achieve a unified and consistent approach to the assessment of cost-effectiveness for anti-dementia therapies. PMID- 17851195 TI - Redox proteomics identification of oxidatively modified brain proteins in Alzheimer's disease and mild cognitive impairment: insights into the progression of this dementing disorder. AB - Alzheimer disease is a common age-related neurodegenerative disease characterized pathologically by senile plaques, neurofibrillary tangles, synaptic disruption, and progressive neuronal deficits. The senile plaques contain amyloid-beta (1-42) and amyloid-beta (1-40), that has been shown by a number of laboratories to induce oxidative stress and as well as neurodegeneration, although the exact mechanisms remained to be defined. Our laboratory showed an increased oxidative stress in AD and MCI brain as indexed by protein oxidation and lipid peroxidation. In the present review, we summarize our finding of oxidatively modified proteins using a redox proteomics approach in AD and MCI brain to investigate the mechanism that may be involved in MCI and AD pathogenesis and discuss our findings in terms of AD progression and pathogenesis. PMID- 17851196 TI - Genetics of Alzheimer's disease. A rapidly evolving field. AB - Genetic factors have a variable impact on Alzheimer's Disease (AD), ranging from familial forms that are transmitted in an autosomal dominant fashion to sporadic AD, where a polygenic component is present. Most genes conferring susceptibility to AD are related to amyloid-beta deposition (APP; PS1; PS2; APOE; Cystatin-C; ubiquilin-1), oxidative stress (NOS2; NOS3) and inflammatory response (IL-1 alpha; IL-1 beta; IL-6; TNF-alpha). Genome-wide analyses, transcriptomics and proteomics approaches have pointed also to proapoptotic genes as increasing AD liability. Depression and psychotic symptoms that occur in a large proportion of AD patients have been associated with monoamine genes coding for metabolic enzymes (COMT), transporters (5-HTTLPR) and receptors (DRD1; DRD3). Genetic testing may be useful to confirm the diagnosis of AD in individuals with clinical signs of dementia, while it is generally not recommended as a predictive testing for AD in asymptomatic individuals. Drugs currently in use to treat AD are effective in only 20% of patients; their therapeutic effect is predominantly under genetic control (CYP26 gene; APOE). Environmental factors have been shown to moderate the effects of genes on psychiatric disorders such as depression, schizophrenia and ADHD. The study of gene-environment interactions in AD, that are still poorly understood, is essential to predict disease-risk in asymptomatic individuals. Genomics will provide a dynamic picture of biological processes in AD and new targets for the forthcoming anti-AD drugs. PMID- 17851197 TI - Unfolded p53: a potential biomarker for Alzheimer's disease. AB - The identification of biological markers of AD can improve diagnostic accuracy and therapy follow-up as well as provide information on the pathogenesis of the disease. We recently found that fibroblasts derived from AD patients expressed an altered conformational status of p53 and were less sensitive to p53-dependent apoptosis compared to fibroblasts from non-AD subjects. When investigating the mechanism of such alteration, we found that the exposure to nanomolar concentrations of amyloid-beta (Abeta) 1-40 peptide induced the expression of an unfolded p53 protein isoform in fibroblasts derived from non-AD subjects. These data suggest that the tertiary structure of p53 and the sensitivity to p53 dependent apoptosis is influenced by low concentrations of soluble Abeta. On this basis, we hypothesized that low amounts of soluble Abeta induce early pathological changes at cellular level that may precede the amyloidogenic cascade. One of these changes is the induction of a novel conformational state of p53. If low amounts of Abeta peptide, not resulting in cytotoxic effects, are responsible for p53 structure changes, it could be possible to consider the unfolded p53 both as an agent participating to the early pathogenesis and as a specific marker of the early stage of AD. PMID- 17851198 TI - Zinc dyshomeostasis, ageing and neurodegeneration: implications of A2M and inflammatory gene polymorphisms. AB - Zinc maintains brain functions because involved in glutaminergic transmission, in antioxidant response and in conferring biological activity to brain enzymes and growth factors. Zinc turnover is mediated by Metallothioneins (MT) which regulate the intracellular free zinc ions [Zn](i). Alterations in zinc homeostasis are associated to various brain dysfunctions, including brain inflammatory status, but little is known about its implication in the aging brain and neurodegeneration. Literature data in experimental animals suggest that zinc dyshomeostasis may occur in aging associated to a decline in brain functions. One of the causes may be an altered homeostasis of MT and other zinc-binding proteins, such as alpha2 macroglobulin (A2M), which are of protection against stress and inflammation during young/adult age but turn into being harmful in aging. In fact, despite total brain zinc content is unchanged in the brain of aged animals, with respect to the young/adult, the activity of some zinc dependent enzymes is impaired and large amount of zinc has been found in the core of Alzheimer's disease senile plaques. The role played by MT and A2M is reported in ageing and Alzheimer's disease and on some polymorphisms of A2M and inflammatory genes (cytokines and their receptors) because some of them may be affected by zinc, via MT homeostasis. PMID- 17851199 TI - Water governance, resilience and global environmental change - a reassessment of integrated water resources management (IWRM). AB - Integrated Water Resource Management (IWRM) is gaining increased acceptance among water policy makers and researchers as a way to create more effective governance institutions, leading towards integrated water development solutions for poverty alleviation, while addressing social, economic and environmental aspects of water challenges. However, global environmental change poses fundamental challenges to water policy makers as it implies vast scientific, and hence, policy uncertainty; its implications for international water governance initiatives remain unspecified, effectively hindering dialogue on how current IWRM initiatives should be modified. This paper addresses the lag between our growing understanding of resilient interconnected freshwater resources (and their governance) and the reforms being promoted by policy makers. In particular, there is a need to rethink some of IWRM's key components to better tackle the challenges posed by the complex behaviour of interconnected social-ecological systems and global environmental change. PMID- 17851200 TI - Flood risk mapping at European scale. AB - The aim of this article is to illustrate a framework for flood risk mapping at pan-European scale produced by the Weather-Driven Natural Hazards (WDNH) action of the EC-JRC-IES. Early results are presented in the form of flood risk index maps. We assess several flood risk factors that contribute to the occurrence of flood disasters. Among the causal factors of a flood disaster one is triggering a natural event in the form of extreme precipitation and consequently extreme river discharge and extreme flood water levels. The threatening natural event represents the hazard component in our assessment. Furthermore exposure and vulnerability are anthropogenic factors that contribute also to flood risk. In the proposed approach, flood risk is considered on the light of exposure, vulnerability and hazard. We use a methodology with a marked territorial approach for the assessment of the flood risk. Hence, based on mathematical calculations, risk is the product of hazard, exposure and vulnerability. Improvements on datasets availability and spatial scale are foreseen in the next phases of this study. This study is also a contribution to the discussion about the need for communication tools between the natural hazard scientific community and the political and decision making players in this field. PMID- 17851201 TI - Climate change and the EU Water Framework Directive: how to deal with indirect effects of changes in hydrology on water quality and ecology? AB - In order to set ecological goals and determine measures for the European Water Framework Directive, the effects of climate change on lake ecosystems should be estimated. It is thought that the complexity of lake ecosystems makes this effect inherently unpredictable. However, models that deal with this complexity are available and well calibrated and tested. In this study we use the ecosystem model PCLake to demonstrate how climate change might affect the ecological status of a shallow peaty lake in 2050. With the model PCLake, combined with a long-term water and nutrient balance, it is possible to describe adequately the present status of the lake. Simulations of future scenarios with increasing precipitation, evaporation and temperature, showed that climate change will lead to higher nutrient loadings. At the same time, it will lead to lower critical loadings. Together this might cause the lake to shift easier from a clear water to a turbid state. The amount of algae, expressed as the concentration Chl-a, will increase, as a consequence turbidity will increase. The outcome of this study; increasing stability of the turbid state of the lake, and thus the need for more drastic measures, is consistent with some earlier studies. PMID- 17851202 TI - New climate change scenarios for the Netherlands. AB - A new set of climate change scenarios for 2050 for the Netherlands was produced recently. The scenarios span a wide range of possible future climate conditions, and include climate variables that are of interest to a broad user community. The scenario values are constructed by combining output from an ensemble of recent General Climate Model (GCM) simulations, Regional Climate Model (RCM) output, meteorological observations and a touch of expert judgment. For temperature, precipitation, potential evaporation and wind four scenarios are constructed, encompassing ranges of both global mean temperature rise in 2050 and the strength of the response of the dominant atmospheric circulation in the area of interest to global warming. For this particular area, wintertime precipitation is seen to increase between 3.5 and 7% per degree global warming, but mean summertime precipitation shows opposite signs depending on the assumed response of the circulation regime. Annual maximum daily mean wind speed shows small changes compared to the observed (natural) variability of this variable. Sea level rise in the North Sea in 2100 ranges between 35 and 85 cm. Preliminary assessment of the impact of the new scenarios on water management and coastal defence policies indicate that particularly dry summer scenarios and increased intensity of extreme daily precipitation deserves additional attention in the near future. PMID- 17851203 TI - Climate change and floods - findings and adaptation strategies for flood protection in Baden-Wurttemberg. AB - The climatic conditions in Southern Germany have changed noticeably in the 20th century, especially during the last three decades. Both in specific regions and interannually, the trends found exceed the natural margins of deviation previously known from long measurement series for some measured quantities. The mean and also the extreme floods are expected to increase significantly, although the results of the model chain global model-regional climate models-water balance models are still uncertain. As a precaution an adaptation strategy has been developed for the field of flood protection which takes into consideration the possible development for the next decades and also takes into account the uncertainties. PMID- 17851204 TI - Impact of summer droughts on water quality of the Rhine River - a preview of climate change? AB - It is generally recognized that climate change will affect the discharge regime of the Rhine River. Especially the anticipated increase in extreme river discharges (floods and droughts) poses serious problems to water management, both with regard to water quantity and water quality. Water quality effects of climate change are not sufficiently recognized, however. The purpose of this study is to investigate the impact of droughts on the water quality of the River Rhine. Time series of river flow and water quality were analyzed for station Lobith, located at the Dutch-German border. Over the past three decades, three major droughts were identified, occurring in the years 1976, 1991, and 2003. The water quality during these dry years was compared with the water quality in reference years, characterized by average hydrological conditions and similar chemical pollution. Four groups of water quality parameters were investigated: 1, general variables (water temperature, dissolved oxygen, chlorophyll-a); 2, major ions (chloride, sodium, sulfate, fluoride, bromide); 3, nutrients; and 4, heavy metals. It was found that water quality is negatively influenced by (summer) droughts, with respect to water temperature, eutrophication, major ions and heavy metals. Effects on nutrient concentrations were small for ammonium and could not be demonstrated for nitrate, nitrite and phosphate. The decline in water quality during summer droughts is both related to the high water temperatures and to low river discharges (limited dilution of the chemical load from point sources). Moreover, the impact of the 1976 drought on water quality was far more important than that of the 2003 drought, indicating that the impact of droughts on water quality will be greater when the water quality is already poor. PMID- 17851205 TI - Vulnerability of Korean water resources to climate change and population growth. AB - Freshwater availability is affected by changes in climate and growth. We assessed the freshwater vulnerability for five major Korean river basins for 2015 and 2030. We used a regional climate model based on the IPCC SRES A2 scenario, US Geological Survey's Precipitation Rainfall Simulation Model, and population and industrial growth scenarios for impact assessment. The model simulation results suggest increasing spatial and temporal variations of water stress for the basins that are already developed. While freshwater is more vulnerable to growth scenarios than the climate change scenario, climate change alone could decrease mean annual runoff by 10% in four major river basins by 2030. As the first national assessment of climate change, we suggest possible adaptive water resource management and policy strategies for reducing climate related risks in Korea. PMID- 17851206 TI - Raising awareness on water and climate related risks - an overview. AB - Climate change is not an easy subject from the perspective of communications studies: it is widely regarded as a most important issue, but its global scope and the lack of consensus on its consequences can make it hard to encompass. This article aims to structure the field and set out the domains of communicative action that are involved, as well identify the actors involved and their role in the overall debate. The different modalities of communication and the dynamics in the use of media in the present time are considered, before discussion of some basic issues with regard to communication, such as the meaning of (scientific) information versus more emotional cues, the opportunities for action that can be offered to citizens/consumers, and the issue of trust in responsible agencies. PMID- 17851207 TI - Framing climate change and spatial planning: how risk communication can be improved. AB - Taking the role of frames into account may significantly add to the tools that have been developed for communication and learning on complex risks and benefits. As part of a larger multidisciplinary study into climate-related forms of sense making this paper explores which frames are used by the citizens of Western European countries and, in particular, the Netherlands. Three recent multi national public opinion surveys were analysed to examine beliefs about climate change in the context of beliefs about energy technology and concerns about other environmental issues, such as natural disasters. It appeared that many citizens had only vague ideas about the energy situation and that these do not constitute an unequivocal frame for climate issues. In contrast, the results suggest that the long-lasting rainfall and severe floods in Central Europe have had a significant impact. Climate change was often framed in a way that articulates its associations with rain- and river-based problems. This result is extremely important for risk communication, because especially in the Netherlands with its vulnerable coastal zones climate change may produce many more consequences than rain- and river-based problems only. PMID- 17851208 TI - Exploring local knowledge of the flooding risk of the Scheldt Estuary. AB - 'The public should be involved in the decision making process' is an oft heard statement, but the practice of public participation remains a worrisome issue for policy makers and planners. In this paper we describe local knowledge of flooding risk in the vicinity of the Scheldt Estuary derived through in-depth, semi structured interviews with fourteen inhabitants. We compare and contrast this knowledge with that of scientists involved in the assessment of the flooding hazard posed by the tidal Scheldt and with that of Dutch and Flemish policy advisors. We identify areas of common knowledge, confirm the accuracy of much local knowledge and recognize the percipience of a number of the questions posed by local inhabitants. This exploratory study serves to confirm that background local knowledge can be a valuable tool in designing responsible policy processes for flood risk management. PMID- 17851209 TI - Application of scenario technique in flood risk management. AB - It is now commonly accepted that the management of flood risks has to be fulfilled within an integrated framework. About two decades ago flood risk was managed from a limited perspective predominantly by means of structural measures aimed at flood control. In contrast integrated flood risk management incorporates the complete management cycle consisting of the phases prevention, protection and preparedness. In theory it is a well described concept. In the stage of implementation, however, there is often a lack of support although a consistent policy framework exists. Consequently, the degree of implementation must be rated as inadequate in many cases. In particular this refers to the elements which focus on preparedness and prevention. The study to which this paper refers emphasises the means and potentials of scenario technique to foster the implementation of potentially appropriate measures and new societal arrangements when applied in the framework of integrated flood risk management. A literature review is carried out to reveal the state-of-the-art and the specific problem framework within which scenario technique is generally being applied. Subsequently, it is demonstrated that scenario technique is transferable to a policy making process in flood risk management that is integrated, sustainable and interactive. The study concludes with a recommendation for three applications in which the implementation of measures of flood damage prevention and preparedness is supported by scenario technique. PMID- 17851210 TI - Integrated flood management. AB - While there have been a number of international initiatives centred around hydrological sciences and technical approaches, the social, economic, environmental, and legal and institutional aspects of flood management have been dealt with sporadically and in a limited manner. WMO and the Global Water Partnership have established the Associated Programme on Flood Management (APFM) to address these issues and developed a concept of Integrated Flood Management (IFM) in 2002. This article is the result of the integrated flood management approaches through pilot projects and multi-disciplinary approaches launched by the initiative since the establishment of the IFM concept. This approach seeks to integrate land- and water-resources development in a river basin, within the context of Integrated Water Resources Management (IWRM) and aims at maximizing the benefits from floodplains and at the same time reducing loss of life from flooding. This approach identified the key elements of IFM and recommended that these can be put in place by: adopting a basin approach to flood management; adopting a multi-disciplinary approach in flood management; reducing vulnerability to and risks from flooding; enabling community participation; and preserving ecosystems; and addressing climate change and variability, supported by enabling mechanism through appropriate legislation and regulations. PMID- 17851211 TI - Tensions in water management: Dutch tradition and European policy. AB - Present-day worldwide water problems require new management tools and sustainable system innovations. At Delft University of Technology research is being carried out into water resources and management development aimed at forming such tools and innovations, focused on Integrated River Basin Management (IRBM). One of the case-studies deals with Dutch water management and technology in the context of European IRBM in the form of the 2000 Water Frame Directive. The Netherlands experience many water problems and European IRBM could bring help by offering a framework for both international cooperation and technological innovations. To work as an adequate management tool European IRBM should be tailored to the Dutch water tradition, which recently culminated in Integrated Water Management. Both approaches are in some respects contradicting. Europe pursues, for example, centralized control; while the Dutch have their strongly water boards based decentralized administration. The tensions between both approaches require mutual adaptation, for which the concept of subsidiarity might offer points of departure. This paper describes the first results of the case-research into Dutch water management and technology in the context of Europe as well as the backgrounds and the set-up of the research as a whole. PMID- 17851212 TI - From optimal to practical safety standards for dike-ring areas. AB - After the flood disaster in 1953 in the southwestern part of the Netherlands, Van Dantzig tried to solve the economic decision problem concerning the optimal height of dikes. His solution has a fixed probability of flooding after each investment. However, when there is economic growth, not the probability of flooding but the expected yearly loss by flooding is the key variable in the real optimal safety strategy. Under some conditions, it is optimal to keep this expected loss within a constant interval. Therefore, when the potential damage increases by economic growth, the flooding probability has to decline in the course of time in order to keep the expected loss between the fixed boundaries. The purpose of the paper is to show the implications of the optimal solution in case there are differences between costs and benefits among dike-ring areas. Further, the paper focuses on the translation of the theoretical results into new legal standards that can work well in practice. PMID- 17851213 TI - Transboundary flood management in the Rhine basin: challenges for improved cooperation. AB - An appropriate institutional set up is essential for efficient transboundary flood management in the Rhine basin, particularly in view of future uncertainties like climate change. Flood management factors are identified based on a historical comparison in the Netherlands and Germany. They include differences in the perception of the problem and how to solve it; in the understanding of key items and how to address them; in administrative responsibilities and the political will to act. Suggestions are made to improve cooperation, in particular to generate a common problem perception and problem analysis, to develop a common vision for future flood strategies and to create a network of discussion platforms to promote social learning and to prepare, decide and implement flood management issues. PMID- 17851214 TI - When climate change is a fact! Adaptive strategies for drinking water production in a changing natural environment. AB - Climate change increases water system dynamics through temperature changes, changes in precipitation patterns, evaporation, and water quality and water storage in ice packs. Water system dependent economical stakeholders, such as drinking water companies in the Netherlands, have to cope with consequences of climate change, e.g. floods and water shortages in river systems, upcoming of brackish ground water, salt water intrusion, increasing peak demands and microbiological activity due to temperature rise. In the past decades, however, both water systems and drinking water production have become more and more inflexible; water systems have been heavily regulated aiming at maximum security and economic functions and the drinking water supply in the Netherlands has grown into an inflexible, but cheap and reliable, system. At a water catchment scale, flexibility and adaptation are solutions to overcome climate change related consequences. Flexible adaptive strategies for drinking water production comprise new sources for drinking water production, application of storage concepts in the short term, and a redesign of large centralized systems, including flexible treatment plants, in the long term. Transition to flexible concepts will take decades because investment depreciation periods of assets are long. These strategies must be based on thorough knowledge of current assets to seize opportunities for change. PMID- 17851215 TI - Participatory dam systems modelling: a case study of the transboundary Guadiana River in the Iberian Peninsula. AB - Modelling tools have been widely used to investigate best management practices. But in contrast to the plethora of modelling studies, the practical implementation of outcomes is comparatively small. There is an urgent need to implement results and to show the practical validation of the concept developed, especially against the context of water stress mitigation. The participative development of modelling studies as a joint effort of stakeholders and modellers is seen as a key to achieve a wider identification, acceptance, trust and applicability of results. Participatory planning in the water sector is also increasingly requested in water management, where tasks have been for clarified decades through different institutional arrangements and national laws. Stakeholder involvement in water resources management have been limited to what was long time seen as participation, merely information on action to be taken. In the last decade the need for participation has been reflected in different ways. In Europe, the implementation of the Water Framework Directive (WFD) under Art. 14, requires all the European countries to involve stakeholders in decision making processes on water resource management. The aim of this paper is to present and discuss the research framework and possible results of investigating dam modelling through participatory systems modelling. We introduce a structured approach to use participatory modelling (PM) for stimulating the integration of modelling and decision making, also as a way of implementation of some articles of the WFD. The results and the framing of this paper are part of the AQUASTRESS Project. The conceptual modelling has been developed by a multidisciplinary research team, local stakeholders and local experts. Some results are discussed and recommendations made. PMID- 17851216 TI - The climate footprint: a practical tool to address climate change. AB - Waternet supplies clean and safe drinking water to the homes of almost one million Amsterdam citizens, and also collects and treats the resulting wastewater, ensuring its safe discharge back into the water system. Climate change poses a growing challenge. Firstly Waternet is affected by the consequences of climate change, such as longer periods of drought and heavier bursts of rainfall. Secondly, the company also plays a role in causing climate change, as emissions from the Amsterdam water chain contribute to global warming. This paper aims to focus attention on mitigation as an inseparable part of adaptation-programmes. The Climate Footprint methodology is applied to the integrated Amsterdam water chain: from the point of withdrawing water from the surface/groundwater water system for drinking water production, to the point of returning the purified wastewater to the surface water/groundwater system. In between, the water is pre-treated with chemicals, transported, purified by dune filtration, again treated for drinking water quality, distributed over the area of Amsterdam, used in households and industries, collected from there by sewers and pumps, transported to purification plants and finally again treated with chemicals and purified to end with acceptable surface water quality. The whole process generates CO(2)-emissions in three different ways: * Sewage treatment transforms the remains of human food consumption into CO(2). These emissions do not originate from fossil fuels, but from food. They remain in a short carbon cycle and do not contribute to global warming. In fact, the sludge remaining from the purification plant is an important energy source. * Transport and purification processes require energy; this results in direct emissions e.g. in the case of fuel or natural gas use, and indirect emissions in the case of electricity. * The use of chemicals and materials for construction, transport systems, and all other facilities and services to keep the system running does require suppliers of these goods and services to consume energy and thus causes indirect emission. An inventory of these three different types of emissions is made for the (about) 1990 situation, the 2004 situation, and prognosticated for the 2007 situation. The 2004 situation reveals a 0.16 ton CO(2) equivalent emission per person. Compared to the worldwide 4 ton emission per person, this would mean a 4% contribution from the urban water system. With all the improvements scheduled, a 50% elimination of greenhouse gas emissions looks attainable for the 2007 situation. Further possibilities for emission reductions may be found by talking to suppliers about the indirect emissions. PMID- 17851217 TI - The closed city as a strategy to reduce vulnerability of urban areas for climate change. AB - Urbanization, land subsidence and sea level rise will increase vulnerability to droughts in the urbanized low-lying areas in the western part of the Netherlands. In this paper a possibility is explored to decrease vulnerability of urban areas by implementing an alternative water supply option. A four component vulnerability framework is presented that includes threshold capacity, coping capacity, recovery capacity and adaptive capacity. By using the vulnerability framework it is elaborated that current water supply strategies in the Netherlands mainly focus on increasing threshold capacity by constructing improved water storage and delivery infrastructure. A complete vulnerability decreasing strategy requires measures that include all four components. Adaptive capacity can be developed by starting experiments with new modes of water supply. A concept which is symbolically called 'the closed city' uses local urban rainfall as the only source of water supply. The 'closed city' can decrease the water dependence of urban areas on (1) the surrounding rural areas that are diminishing in size and that are increasingly under strain and (2) river water resources that will probably be less constant and reliable as a result of climate change. PMID- 17851218 TI - Toxic encephalopathy and noise-induced hearing loss. AB - In several laboratory animal studies, it has been documented that the hearing, vision, and brain can be injured due to exposure to organic solvents. This finding formed the background for a pilot study (n=16) aimed at identifying new ways of qualifying diagnostics, treatment, and rehabilitation of patients suffering from brain injury due to exposure to organic solvents, also referred to as toxic encephalopathy. Diagnosing toxic encephalopathy is complicated because the symptoms of this type of diffuse brain injury are non-specific. So, it was initially hypothesised that some of the difficulties involved in diagnosing toxic encephalopathy could be minimized by extending the diagnostic procedure. Apart from clinical interviewing and neuropsychological testing, the diagnosis should include the examination of hearing and vision. This will help in achieving new measures that could improve in diagnosing toxic encephalopathy with more certainty. On the basis of ranking, only one patient in the pilot study was considered to have a normal neuropsychological test profile, which was defined as a test profile without any marked deviations when compared with a normal population. A total of 10 patients were considered to have "discrete problems." These patients had a test profile showing either a few strikingly negative results or an array of results slightly below the expected level when compared with a normal population. A total of four patients were considered to suffer from "moderate problems" and one patient from "severe problems." The patients with "moderate problems" and "severe problems" showed consistent negative results and an unambiguous negative test profile. However, the overall results of all neuropsychological examinations performed revealed a dispersed picture. Quite remarkably, all the 13 patients who had their hearing examined showed a loss of hearing, 7 patients complained about tinnitus, and all patients had a history of exposure to both noise and organic solvents, which had not been observed at the initial examination, but seemed to have serious implications for their prognosis and future life. PMID- 17851219 TI - The use of hearing protection devices by older adults during recreational noise exposure. AB - A population-based study to assess the use of hearing protection devices by older adults during noisy recreational activities was performed. The population-based Epidemiology of Hearing Loss Study was designed to measure the prevalence of hearing loss in adults residing in Beaver Dam, Wisconsin. The use of hearing protection devices during noisy recreational activities was assessed by performing three examinations over a period of 10 years (1993-1995, no. of participants (n)=3753, aged 48-92 years; 1998-2000, n=2800, aged 53-97 years; 2003-2005, n=2395, aged 58-100 years). The recreational activities included hunting, target shooting, woodworking/carpentry, metalworking, driving loud recreational vehicles, and performing yard work using either power tools or a chain saw. The prevalence of using hearing protection devices during any of these activities increased with time (9.5%, 15.0%, and 19.9% at baseline, 5 years, and 10 years, respectively). However, the use of hearing protection devices remained low for most activities. Those under the age of 65 were twice as likely to use hearing protection devices during noisy activities than were older adults. Men, those with a hearing handicap, and those with significant tinnitus were more likely to use hearing protection devices. Smokers and the less educated were less likely to use hearing protection devices. The results demonstrated that many adults expose themselves to potentially damaging recreational noise, leaving them at risk for hearing loss. PMID- 17851220 TI - The development of Weinstein's noise sensitivity scale. AB - Many studies have shown the significant correlation between noise annoyance and noise sensitivity identified by Weinstein's noise sensitivity scale (WNS). However, the validity of the scale has not been sufficiently assessed. This study was designed to investigate the validity of each question in WNS and to develop a more valid noise sensitivity measurement scale. A questionnaire study was conducted in a residential area along trunk roads in Kusatsu, Japan, and 301 responses were collected. In this paper, noise sensitivity was defined as the factor that induced individual variability in reactions caused by noise exposure and that is not affected by the noise exposure. The relationship between noise exposure and answers to each question in WNS was investigated by multiple logistic regression analysis, and the influence of response bias on the score of WNS was examined. The results showed that WNS contained some questions that were inappropriately related to noise exposure level and that the score was affected by response bias. The reported correlation between annoyance and the score of WNS could be confounded by noise exposure and response bias. A noise sensitivity measurement scale named WNS-6B was newly developed, excluding the biased questions from the original WNS and applying binary coding to six-response options in order to reduce the response bias. WNS-6B seemed to be more appropriate to assess noise sensitivity than the original scale. PMID- 17851221 TI - Associations between noise sensitivity and sleep, subjectively evaluated sleep quality, annoyance, and performance after exposure to nocturnal traffic noise. AB - In order to determine the influence of noise sensitivity on sleep, subjective sleep quality, annoyance, and performance after nocturnal exposure to traffic noise, 12 women and 12 men (age range, 19-28 years) were observed during four consecutive nights over a three weeks period. After a habituation night, the participants were exposed with weekly permuted changes to air, rail and road traffic noise. Of the four nights, one was a quiet night (32 dBA), while three were noisy nights with exposure to equivalent noise levels of 39, 44, and 50 dBA in a permuted order. The traffic noise caused alterations of most of the physiological parameters, subjective evaluation of sleep, annoyance, and performance. Correlations were found between noise sensitivity and subjective sleep quality in terms of worsened restoration, decreased calmness, difficulty to fall asleep, and body movements. The results suggest that alterations of subjective evaluation of sleep were determined by physical parameters of the noise but modified by individual factors like noise sensitivity. PMID- 17851222 TI - The reliability of the noise sensitivity questionnaire in a cross-national analysis. AB - Noise sensitivity is regarded as a relevant predictor for annoyance reactions. Since many studies have focused on noise sensitivity at an international level, the present analysis was conducted to detect national peculiarities concerning noise sensitivity. Using the approach of the generalizability theory, reliability of the noise sensitivity questionnaire was analyzed taking into consideration relevant facets assumed to contribute to the measurement error. A total of 126 individuals from seven European countries participated in this study. The reliability coefficients for the global noise sensitivity score ranged from 0.90 to 0.91. It was determined that the translated questionnaires are comparable. PMID- 17851223 TI - The development of the noise sensitivity questionnaire. AB - The existing questionnaires for determining the noise sensitivity of individuals provide information only about global noise sensitivity, although empirical data suggest that measuring noise sensitivity for different situations in daily life might be more logical. Therefore, the "Noise-Sensitivity-Questionnaire" (NoiSeQ) was developed to measure global noise sensitivity as well as the sensitivity of five domains of daily life, namely, leisure, work, habitation, communication, and sleep. The assessment of the measurement characteristics was based on the Generalizability (G) theory. The results of the G-study (N=66) proved that a single application of the questionnaire is sufficient for determining an individual's noise sensitivity. Furthermore, the ratings are age and gender independent. The subsequently conducted Decision (D)-study (N=288) provides information on the reliability of NoiSeQ. If the questionnaire is used for measuring global noise sensitivity, the reliability (relative and absolute G coefficient) reaches a value above 0.90. According to ISO 10075-3, the questionnaire satisfies the precision level 1 "accurate measurement" in this case. The G-coefficients for all the subscales exceed the lower limit 0.70, with the exception of subscale leisure, which did not prove satisfactory. However, this subscale can reach a reliability of more than 0.70 if additional items are included. The validity of the instrument was proven for the subscales habitation (N=72) and work (N=72). In both the studies, the participants were asked to rate the annoyance in the presence of several rail and traffic noise scenarios. The subjects were characterized as low and high noise sensitive according to their sensitivity values obtained from NoiSeQ. In conclusion, a significant difference in annoyance rates was observed between the low and high noise sensitive groups for both the subscales habitation and work. This data support the validity of NoiSeQ. PMID- 17851224 TI - AL amyloidosis with renal involvement. AB - Primary (AL amyloidosis) is a systemic disease characterized by an amyloid deposition process in many organs, with unsatisfactory survival of patients. The monoclonal light chains form the fibrils that deposit and accumulate in tissues. Renal involvement is very frequent in AL amyloidosis and could lead to development of nephrotic syndrome followed by the renal failure in many cases. Classic therapeutic combination melphalan and prednisone has been supplemented with drugs with different mechanisms of action in this group of patients: high dose dexamethasone, high-dose dexamethasone with melphalan, combination of vincristine, doxorubicin, and dexamethasone or newly high-dose melphalan supported by peripheral blood stem cell transplantation. This progressive therapy leads to the better survival and prognosis in the majority of patients. Alternative therapeutic approaches include thalidomide (alone or in combination with cyclophosphamide), lenalidomide, iododoxorubicin, etanercept and rituximab. The development of immunotherapy is expected in the near future. PMID- 17851225 TI - MDR1 single nucleotide polymorphisms predict response to vinorelbine-based chemotherapy in patients with non-small cell lung cancer. AB - BACKGROUND: The polymorphisms of genes participate in metabolism and transport, and therefore may have an impact on the response to vinorelbine. OBJECTIVES: To investigate whether genotypes of CYP3A5, MDR1 and cyclooxygenase-2 (COX-2) are associated with the response to vinorelbine in non-small cell lung cancers (NSCLC). METHODS: We determined the genotypes of CYP3A5(*3), MDR1 (2677G-->T at exon 21 and 3435C-->T at exon 26 and their haplotypes) and COX-2 (-1195G-->A) polymorphisms by PCR-RFLP and chemotherapy response in 69 Chinese Han patients with NSCLC who received a combination chemotherapy of vinorelbine-cisplatin (VC). The chi(2) test was used to investigate potential associations between genotypes and response to chemotherapy. Odds ratios and 95% confidence intervals were calculated. RESULTS: The 3435 CC genotype was associated with a significantly better chemotherapy response compared with the combined 3435 CT and TT genotypes (p = 0.025). The 2677 GG genotype was also associated with a better chemotherapy response compared with the combined 2677 GT and TT genotype, although it was not statistically significant. Moreover, we analyzed the haplotypes of MDR1 3435 2677: patients harboring the 2677G-3435C haplotype had a statistically significantly better response to chemotherapy compared with those with the other haplotypes combined (p = 0.015). CYP3A5*3 is not likely to correlate with sensitivity to vinorelbine in NSCLC. COX-2 (-1195G) is likely to result in a better response to vinorelbine (nonsignificant). CONCLUSIONS: Our findings suggest that MDR1 2677G-->T/A and 3435C-->T polymorphisms can be used to predict treatment response to VC chemotherapy in NSCLC patients. PMID- 17851226 TI - Roles of ghrelin and leptin in the control of reproductive function. AB - Reproductive function in mammals, defined as the capacity to generate viable male and female gametes, and to support pregnancy and lactation selectively in the female, is sensitive to the metabolic state of the organism. This contention, long assumed on the basis of intuitive knowledge, became formulated on a scientific basis only recently, with the identification of a number of neuroendocrine signals which crucially participate in the joint control of energy balance and reproduction. A paradigmatic example in this context is the adipocyte derived hormone, leptin; a satiety factor which signals the amount of body energy (fat) stores not only to the circuits controlling food intake but also to a number of neuroendocrine axes, including the reproductive system. More recently, the reproductive dimension of another metabolic hormone, namely the orexigenic stomach-secreted peptide, ghrelin, has been disclosed by observations on its putative roles in the control of gonadal function and gonadotropin secretion. Of note, leptin and ghrelin have been proposed to act as reciprocal regulators of energy homeostasis. However, their potential interplay in the control of reproduction remains largely unexplored. Based on the comparison of the biological actions of leptin and ghrelin at different levels of the hypothalamic pituitary-gonadal axis, reviewed in detail herein, we propose that, through concurrent or antagonistic actions, the leptin-ghrelin pair is likely to operate also as modulator of different reproductive functions, thereby contributing to the physiological integration of reproduction and energy balance. PMID- 17851227 TI - Progression of fibrosis in usual interstitial pneumonia: serial evaluation of the native lung after single lung transplantation. AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Usual interstitial pneumonia (UIP) is the histopathological pattern identifying patients with the clinical entity of IPF. Despite aggressive immunosuppressive therapy the clinical course is usually dismal. For selected patients only lung transplantation improves prognosis and quality of life. After lung transplantation patients often receive a potent cyclosporine-based immunosuppressive therapy. Some reports suggest that cyclosporine has the potential to prevent progression of fibrosis. OBJECTIVE: In patients with single lung transplantation (sLTx) for UIP we evaluated the effect of cyclosporine-based immunosuppressive therapy on progression of fibrosis using a high-resolution computed tomography (HRCT) scoring system. METHODS: This retrospective observational study included 13 patients (24-64 years old) with histologically confirmed UIP who had HRCT scans preceding and following sLTx and who survived at least 6 months after sLTx. All patients were initially treated with cyclosporin A, prednisone and azathioprine. Three radiologists analyzed HRCT scans by setting a score regarding fibrosis [fibrosis score (FS); range 0-5 for each lobe] and ground-glass opacity [ground-glass score (GGS); range 0-5 for each lobe]. A comparison of serial changes (interval: 12-96 months posttransplant, 2-4 HRCT examinations/patient) was performed with the sign test. RESULTS: Mean pretransplant FS and GGS of the nontransplanted lung were 1.80 and 1.61, respectively. Comparing pre- and posttransplant HRCT scans, mean lung FS significantly increased (0.35 +/- 0.15/year; p = 0.00024), while GGS tended to decrease (0.06 +/- 0.26/year; p = 0.5). CONCLUSION: A cyclosporin A based triple immunosuppressive regimen following sLTx does not seem to prevent progression of the fibrotic changes of the native lung in patients with IPF. PMID- 17851228 TI - Mitral valvular interstitial cells demonstrate regional, adhesional, and synthetic heterogeneity. AB - BACKGROUND/AIMS: Because various regions of the mitral valve contain distinctive extracellular matrix enabling the tissues to withstand diverse mechanical environments, we investigated phenotype and matrix production of porcine valvular interstitial cells (VICs) from different regions. METHODS: VICswere isolated from the chordae (MCh), the center of the anterior leaflet (AlCtr), and the posterior leaflet free edge (PlFree), then assayed for metabolic, growth, and adhesion rates; collagen and glycosaminoglycan (GAG) production, and phenotype using biochemical assays, flow cytometry, and immunocytochemistry. RESULTS: The AlCtr VICs exhibited the fastest metabolism but slowest growth. PlFree cells grew the fastest, but demonstrated the least smooth muscle alpha-actin, vimentin, and internal complexity. AlCtr VICs secreted less collagen into the culture medium but more 4-sulfated GAGs than other cells. Adhesion-based separation resulted in altered secretion of sulfated GAGs by MCh and AlCtr cells but not by the PlFree cells. CONCLUSIONS: VICs isolated from various regions of the mitral valve demonstrate phenotypic differences in culture, corresponding to the ability of the mitral valve to accommodate the physical stresses or altered hemodynamics that occur with injury or disease. Further understanding of VIC and valve mechanobiology could lead to novel medical or tissue engineering approaches to treat valve diseases. PMID- 17851229 TI - Sexual dysfunction in peritoneal dialysis patients. AB - BACKGROUND/AIMS: Sexual dysfunction in patients undergoing peritoneal dialysis (PD) is highly prevalent, but studies addressing this issue are scarce. This cross-sectional study aims to evaluate sexual dysfunction and the determinants among PD patients. METHODS: All chronic PD patients in 8 PD centers were asked to complete a self-reported questionnaire - the International Index of Erectile Function (IIEF) for men and the Index of Female Sexual Function (IFSF) for women so that sexual function could be assessed. They also answered the Beck Depression Inventory (BDI) to measure depressive symptoms. RESULTS: Among 294 patients invited for study, 54 men (mean age 48.8 +/- 10.8 years) and 45 women (mean age 43.6 +/- 7.4 years) were willing to and completed the sexual function questionnaires. The median IIEF score in the men was 56.25. The prevalence of erectile dysfunction, identified by the score in erectile domain of IIEF T transition at -1306 displayed a strong association with several cancers. Our study investigated whether or not the MMP-2 -1306C>T polymorphism contributed to the development of breast cancer (BC) in a Mexican population. METHODS: 90 patients with BC and 96 control subjects were analyzed to detect MMP-2 -1306C>T polymorphism. RESULTS: The frequency of MMP-2 CC genotype was significantly higher in BC patients when compared with the control group (OR 2.15; 95% CI 1.1-4.1). MMP-2 CC genotype frequency was more pronounced in younger subjects (< or =50 years) at diagnosis (OR 2.66; 95% CI 1.04-6.96). CONCLUSION: The data suggest that MMP-2 -1306C>T polymorphism strongly contributes to the development of BC in the population studied, especially among women 50 years old and younger. PMID- 17851254 TI - Nonlinear analyses of heart rate variability in monochorionic and dichorionic twin fetuses. AB - AIMS: To examine whether the heart rate dynamics of a monochorionic diamniotic (MD) twin fetus is different from a dichorionic diamniotic (DD) twin fetus by nonlinear methods of time series analysis. METHODS: 32 fetal heart rate (FHR) recordings from healthy MD twin fetuses and 58 recordings from healthy DD twin fetuses were used. Nonlinear analyses included attractor reconstruction, calculation of the largest Lyapunov exponents, and estimation of correlation dimension. RESULTS: FHR of healthy twin fetuses was shown to have unique nonlinear characteristics. The largest Lyapunov exponent significantly increased during the pregnancy period. In 30-36 weeks, correlation dimension in MD twins was significantly lower than that in DD twins. In DD twins, we observed a significant increase of correlation dimension from 22-29 to 30-36 weeks. In 22-29 weeks, the difference of the values of correlation dimension in each MD twin pair was significantly lower than that in each DD twin pair. CONCLUSIONS: The heart rate dynamics of healthy MD and DD twin fetuses becomes more chaotic according to gestational age. From the viewpoint of the FHR-regulating system, a pair of MD twins seems to have a more strict binding than a pair of DD twins before 30 weeks' gestation. PMID- 17851255 TI - Placenta percreta leading to spontaneous complete uterine rupture in the second trimester. Example of a fatal complication of abnormal placentation following uterine scarring. AB - A 30-year-old gravida 2 para 1 was admitted to hospital 2 years after cesarean section at 20 weeks' gestation with acute onset of abdominal pain and hypovolaemic shock. Emergency laparotomy revealed a uterine rupture located in the anterior uterine wall caused by a placenta percreta and supracervical hysterectomy was performed. This site of invasion and finally rupture was in projection of the previous lower-segment cesarean section. This report illustrates the dramatic consequences of abnormal placentation after prior uterine surgery, which can already occur early during pregnancy and prior to the onset of labour. PMID- 17851256 TI - Ligation of Toll-like receptor 3 differentially regulates M2 and M3 muscarinic receptor expression and function in human airway smooth muscle cells. AB - BACKGROUND: Viral infection causes asthma exacerbations and airway hyperreactivity. Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA) of viral or synthetic origin in a fashion different from protein kinase R (PKR). The aim of this study was to examine the expression and function of TLR3 in human airway smooth muscle (ASM) cells. METHODS: Expression of TLR3 and muscarinic receptor (MR), histamine receptor (HR), and cysteinyl leukotriene receptor (CysLTR) subtypes was analyzed by quantitative real-time PCR, flow cytometry, or Western blotting. It was assessed whether ASM cells respond to polyinosinic-polycytidylic acid (poly I:C), a synthetic analog of dsRNA, with alterations in M2R, M3R, H1R, and CysLT1R expression. The function of these subtypes was evaluated by cholinergic regulation of forskolin-stimulated cyclic AMP accumulation or by mobilization of intracellular calcium upon stimulation. RESULTS: ASM cells expressed TLR3 and PKR, and intracellular TLR3 expression was demonstrated. Poly I:C caused decreased M2R and increased M3R expression, without affecting H1R and CysLT1R expression. Poly I:C-treated cells showed decreased cholinergic inhibition of forskolin-stimulated cyclic AMP accumulation and enhanced calcium flux in response to acetylcholine, but not to histamine and LTD4. These modulating effects of poly I:C were reversed by chloroquine, but not by 2-aminopurine. CONCLUSIONS: The data indicate that poly I:C internalized by ASM cells differentially regulates M2R and M3R expression and function by interacting with TLR3 rather than with PKR, suggesting that these changes may contribute to airway hyperreactivity. PMID- 17851257 TI - Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. AB - BACKGROUND: Several lines of evidence suggest a role of inflammatory processes in Parkinson disease, although it is still unclear whether inflammation is a cause or rather a consequence of neurodegeneration. METHODS: In a prospective population-based cohort study among 6,512 participants aged >or=55 years, with repeated in-person examination, we evaluated the association between cumulative use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of Parkinson disease. Complete information on filled prescriptions was available from automated pharmacy records. Data were analyzed by means of Cox proportional hazards regression analysis, adjusted for age, sex, smoking habits and coffee consumption. RESULTS: After an average 9.4 years of follow-up, 88 new cases of Parkinson disease were detected. No association was found between use of NSAIDs and the risk of Parkinson disease (adjusted hazard ratio for any NSAID use, 1.50; 95% confidence interval, 0.95-2.37). CONCLUSION: Our findings do not support the hypothesis that NSAIDs might decrease the risk of Parkinson disease. PMID- 17851258 TI - Mortality from neurodegenerative disease and exposure to extremely low-frequency magnetic fields: 31 years of observations on Swiss railway employees. AB - AIMS: The objective of the present study was to investigate the relationship between extremely low-frequency magnetic field (ELF-MF) exposure and mortality from several neurodegenerative conditions in Swiss railway employees. METHODS: We studied a cohort of 20,141 Swiss railway employees with 464,129 person-years of follow-up between 1972 and 2002. For each individual, cumulative exposure was calculated from on-site measurements and modelling of past exposure. We compared cause-specific mortality in highly exposed train drivers (mean exposure: 21 microT) with less exposed occupational groups (for example station masters: 1 microT). RESULTS: The hazard ratio for train drivers compared to station masters was 1.96 [95% confidence interval (CI) = 0.98-3.92] for senile dementia and 3.15 (95% CI = 0.90-11.04) for Alzheimer's disease. For every 10 microT years of cumulative exposure senile dementia mortality increased by 5.7% (95% CI = 1.3 10.4), Alzheimer's disease by 9.4% (95% CI = 2.7-16.4) and amyotrophic lateral sclerosis by 2.1% (95% CI = -6.8 to 11.7). There was no evidence for an increase in mortality from Parkinson's disease and multiple sclerosis. CONCLUSIONS: This study suggests a link between exposure to ELF-MF and Alzheimer's disease and indicates that ELF-MF might act in later stages of the disease process. PMID- 17851259 TI - Carotid intima-media thickness and cognitive function in elderly women: a population-based study. AB - OBJECTIVE: Several vascular risk factors have been linked to cognitive decline. However, little is known about the association between the atherosclerotic process and cognitive impairment. We investigated whether carotid intima-media thickness (IMT) predicts the risk of cognitive impairment and whether the putative impairment is specific for some cognitive domains. METHODS: A 12-year population-based follow-up study was performed for a total of 91 women, aged 60 70 years at baseline. Ultrasonographically assessed carotid artery IMT and the Mini-Mental State Examination test were performed at baseline and 12-year follow up. A detailed cognitive evaluation for memory and cognitive speed was performed in 2003. The mean of left and right carotid bifurcation IMT was used in the analyses for association with the risk for poor cognitive speed and memory. RESULTS: Increased IMT at baseline was an independent predictor for poor memory (beta = -5.004, 95% confidence interval = -7.74 to -2.27; p = 0.001) and cognitive speed (beta = 2.562, 95% confidence interval = 1.19-4.94; p = 0.035) at 12-year follow-up after adjustment for age, education, depression, plasma LDL cholesterol, systolic blood pressure, cardiovascular disease, hormone replacement therapy, smoking, alcohol consumption and physical activity. The risk for poor memory (p = 0.023 for linear trend) and cognitive speed (p = 0.070 for linear trend) increased with increasing IMT tertiles. CONCLUSIONS: Carotid IMT predicts an increased risk for cognitive impairment, particularly poor memory and cognitive speed, in elderly women. PMID- 17851260 TI - Plasma titers of antibodies against Epstein-Barr virus BZLF1 and risk of multiple sclerosis. AB - BACKGROUND/AIMS: Results of recently conducted prospective studies have demonstrated that the presence of high titers of anti-EBNA-1 or anti-EBNA complex IgG antibodies in healthy individuals is a strong risk factor for multiple sclerosis (MS). Antibodies to BZLF1, the product of the homonymous early lytic gene, have been found to be related to risk of nasopharyngeal carcinoma, but have not been previously measured in MS studies. METHODS: We examined whether high levels of anti-BZLF1 IgG antibodies also predict MS risk in a nested case-control study among women in the Nurses Health Study and Nurses Health Study II cohorts. RESULTS: Results of this prospective study suggest that antibody titers to EBNAs are the strongest predictor of MS risk. CONCLUSION: Little further contribution may be provided by measuring anti-BZLF1 antibodies in regard to MS risk. PMID- 17851261 TI - Prevalence of stroke in an urban, mixed-income community in Lagos, Nigeria. AB - BACKGROUND: The burden of cerebrovascular disease in developing countries is projected to be on the rise. However, data on the current epidemiology of stroke in Africa are sparse. METHODS: Using a 3-staged method, we conducted a door-to door study of stroke in an urban, mixed-income community in Lagos, Nigeria. We used a modification of the WHO protocol in the first stage, a stroke-specific questionnaire in the second stage and neurological examination of all persons screening positive for stroke in the third stage. We also examined an equal number of stroke-negative persons. RESULTS: Overall, the crude prevalence rate of stroke in urban Nigeria was 1.14/1,000 (males: 1.51; females: 0.69). The age adjusted prevalence rates per 1,000 (adjusted to the USA population 2000) in mid decade strata showed a trend of increasing prevalence with advancing age as follows: 35-44 years = 0.009, 45-54 years = 0.33, 55-64 years = 0.71, 65-74 years = 0.98, 75-84 years = 2.04 and >85 years = 0.74. CONCLUSIONS: Stroke prevalence rates in urban Nigeria are lower than those in most developed countries. The lower rates may be related to lower incidence and higher stroke mortality in developing countries. PMID- 17851262 TI - A phase I study of concurrent chemoradiotherapy with S-1 for T2N0 glottic carcinoma. AB - OBJECTIVE: Chemoradiation based on S-1, a novel oral antitumor agent of fluorinated pyrimidines, is the treatment for T2N0 glottic carcinoma; however, the optimal scheduling and dosing have still not been established. A phase I study was conducted to determine the maximum tolerated dose of S-1 with radiotherapy of 2 Gy/day for 5 days a week to a total dose of 60 Gy. Endpoints of this study were to examine the toxicity profile of this regimen and to determine the recommended dose of S-1. METHODS: Concomitant administration with the above mentioned radiotherapy of S-1 once a day for 2 weeks, beginning on the day therapy was started, followed by 2 weeks off the drug and 2 weeks on the drug with the dose escalating from S-1 60 mg/body (level 1) to 80 mg/body/day (level 2), and then to 100 mg/body/day (level 3). RESULTS: Twenty-one patients were valid for safety. Eighteen patients were enrolled in the dose-escalation phase. In all patients, S-1 was administered. The maximum tolerated dose was determined to be 100 mg/body/day and the dose-limiting toxicity was indicated by the onset of grade 3 chemoradiation dermatitis. Therefore, the determined recommended dose of S-1 was 80 mg/body/day. Objective response according to Response Evaluation Criteria in Solid Tumors were observed in 20 of 21 patients who had measurable disease (95.2%). CONCLUSION: Concurrent S-1 and radiotherapy was feasible and well tolerated, and was suggested to produce a worthwhile response in T2N0 glottic carcinoma. These results warrant further investigation, and a phase II has already been started. PMID- 17851263 TI - Do elderly cancer patients achieve an adequate dose intensity in common clinical practice? AB - BACKGROUND: Elderly patients rarely receive adequate dose intensity (DI) using conventional regimens. Possible causes are improper patient assessment, the chemotherapy (CT) regimen chosen, the number and severity of comorbidities, patient compliance and physician experience. To explore this issue, DI was retrospectively analyzed in elderly patients treated with conventional CT regimens for advanced solid cancer. PATIENTS AND METHODS: Patients > or =69 years were evaluated. All patients had metastatic solid tumors. Comorbidities, performance status (PS), toxicities, number of CT cycles, dose reduction and discontinuation of treatment were recorded. Relative DI (RDI) was calculated and regressed against these parameters. RESULTS: 108 patients were eligible. The most frequent diagnoses were: lung, head-and-neck and colorectal cancer. In 48 patients (44%), their initially scheduled treatment was modified. Mean RDI was 79% (range 19-100%, SD 20.6). Grade 3/4 non-hematological and hematological toxicity occurred in 27 (35/130) and 8% of patients (11/130), respectively. In regression analysis, RDI was significantly associated with hematological toxicity. RDI affected response rate but not overall survival. CONCLUSIONS: RDI is significantly affected by toxicity. These data suggest the importance of the treatment schedule and patient selection as predictorsof adequate treatment. Some non-ratable variables, however, might also play a role regarding the dose intensity delivered. PMID- 17851264 TI - Transport barriers in transscleral drug delivery for retinal diseases. AB - Transscleral delivery has emerged as an attractive method for treating retinal disorders because it offers localized delivery of drugs as a less invasive method compared to intravitreal administration. Numerous novel transscleral drug delivery systems ranging from microparticles to implants have been reported. However, transscleral delivery is currently not as clinically effective as intravitreal delivery in the treatment of retinal diseases. Transscleral drug delivery systems require drugs to permeate through several layers of ocular tissue (sclera, Bruch's membrane-choroid, retinal pigment epithelium) to reach the neuroretina. As a result, a steep drug concentration gradient from the sclera to the retina is established, and very low concentrations of drug are detected in the retina. This steep gradient is created by the barriers to transport that hinder drug molecules from successfully reaching the retina. A review of the literature reveals 3 types of barriers hindering transscleral drug delivery: static, dynamic and metabolic. While static barriers have been examined in detail, the literature on dynamic and metabolic barriers is lacking. These barriers must be investigated further to gain a more complete understanding of the transport barriers involved in transscleral drug delivery. PMID- 17851265 TI - Intrafamilial clinical heterogeneity associated with a novel mutation of the retinal degeneration slow/peripherin gene. AB - AIMS: To identify the phenotypic variations in 6 related individuals affected by a novel mutation in the retinal degeneration slow/peripherin gene. METHODS: Ten family members underwent ophthalmologic assessment with slit-lamp biomicroscopy, dilated fundus examination, fundus photography, autofluorescence imaging and electrophysiological tests. Genomic DNA was extracted from blood samples of all family members (n = 15) using the standard salting-out procedure. RESULTS: The novel C165R mutation was identified in 8 individuals. Of these 8 patients, only 6 gave consent to the clinical study. They had a retinal disease characterized by an adulthood onset of symptoms, and their best corrected visual acuity was between 20/50 and 20/20. Fundus examination showed that 3 patients had typical fundus flavimaculatus: 1 had butterfly-shaped pattern dystrophy and 2 had incipient retinal changes. CONCLUSION: We identified a novel mutation of the retinal degeneration slow/peripherin gene in a family affected by different patterns of retinal dystrophy. This is the first report of an association of fundus flavimaculatus with butterfly-shaped pattern dystrophy. PMID- 17851266 TI - Protective effect of viscoelastics against retina lipid peroxidation. AB - Viscoelastics or ophthalmic viscosurgical devices are routinely used during anterior segment surgery and also in posterior segment surgery. Studies of the harmful effects of phacoemulsification on corneal endothelial cells suggest that much of this damage is mediated by free radicals. In this study, we compare the possible effects against lipid peroxidation in the retina of three different viscoelastic substances: Viscoat, Healon and Visiol. Herein we demonstrate for the first time that viscoelastics are effective to protect the retina against lipid peroxidation, as can be seen by the slight increase of malondialdehyde in the homogenates incubated with viscoelastic exposed to light and to a temperature of 37 degrees C when compared with the control homogenates. PMID- 17851267 TI - Effects of tear substitutes on conjunctival epithelium of mice. AB - AIM: The effects of the administration of three tear substitutes on normal conjunctival epithelium of the mouse, with particular regard to goblet cells, were studied. METHODS: Three-month-old Swiss CD 1 mice were divided into four groups of 7 animals each. Group 1 was untreated (control). The other animals were treated with the instillation of 5 drops/day for 10 days as follows: group 2, 0.2% sodium hyaluronate (SH); group 3, 0.5% hydroxypropylmethylcellulose (HPMC); group 4, 0.9% NaCl. The entire conjunctiva was processed for light and electron microscopy. A morphometric study was performed to evaluate: the number and size of goblet cells and the number, size and optical density of mucin granules. Furthermore, Alcian blue/periodic acid-Schiff (AB/PAS) staining for goblet cells was carried out. RESULTS: The SH-treated group showed that the area and number of goblet cells were similar to the untreated group; the mucin granules were reduced in number and optical density but increased in size. The HPMC-treated group showed a reduced area of goblet cells with reduced optical density of mucin granules. The saline-treated group showed that goblet cells were reduced in area and number; mucin granules showed a reduction in number and optical density and an increased size. The AB/PAS stain showed that each treatment was able to induce a treatment-specific modification of the staining characteristics of goblet cells. CONCLUSION: Our results strongly suggest that tear substitutes can induce treatment-specific modifications of the conjunctival epithelium with particular regard to goblet cell structure and ultrastructure. PMID- 17851268 TI - The relationship between the adhesion characteristics of acrylic intraocular lens materials and posterior capsule opacification. AB - PURPOSE: To investigate the relationship between the adhesion characteristics of similarly designed hydrophobic acrylic intraocular lenses (IOLs) and posterior capsule opacification (PCO). METHODS: Three similarly shaped hydrophobic acrylic IOLs with a sharp-edged optic were used. Adhesive force of IOLs was measured with a tackiness tester. Human lens epithelial cells (LECs) were grown on each IOL for 48 h. LECs were then stained with crystal violet, which served as an index of the amount of cells attached to IOLs. Cellular migration and proliferation assays were performed using chamber inserts containing a collagen membrane. After 96 h of incubation, the collagen membranes were stained with hematoxylin and eosin for analysis. Three similarly shaped IOLs were implanted in rabbits. The eyes were enucleated 3 weeks later and analyzed for PCO area. RESULTS: Hydrophobic acrylic IOLs were classified into three groups: A (less adhesive), B (moderately) and C (highly). The migration area of LECs on the collagen membrane was 5.65 +/- 4.5% in group A, 2.83 +/- 2.1% in group B, and 1.41 +/- 1.5% in group C, with a significant difference between groups A and C (p < 0.05). The mean percentage area of PCO in the rabbit eye was 19.4 +/- 16.7% in group A, 17.5 +/- 8.5% in group B, and 5.5 +/- 3.8% in group C, with a significant difference between groups A and C (p < 0.05). CONCLUSION: Adhesive force of hydrophobic acrylic IOLs may play an important role in preventing PCO. Among the similarly shaped hydrophobic acrylic IOLs, IOLs of highly adhesive material inhibited LEC migration and PCO more than IOLs of less adhesive material. PMID- 17851269 TI - Multifocal electroretinogram responses of the clinically normal retinal areas in diabetes. AB - AIMS: To investigate the degree of implicit time delay in aretinopathic hexagons according to the grading of diabetic retinopathy and factors that affect the mfERG responses of aretinopathic areas. METHODS: MfERG was recorded using the RETIscan system (Roland consult, Brandenbrug, Germany) in 40 eyes of 20 nondiabetic controls, 32 eyes of 16 diabetic patients without retinopathy, and 96 eyes of 48 diabetic patients with nonproliferative diabetic retinopathy (NPDR). Hexagons are divided into retinopathic and aretinopathic hexagons, which were selected using fundus photographs and fluorescence angiography. Relative amplitude and implicit time delay were compared between patient groups and controls. RESULTS: The mean implicit time delay in aretinopathic hexagons was significantly different between each subject group and correlated with the retinopathy severity of the whole retina, as well as in retinopathic hexagons. In all three NPDR groups, implicit time was significantly more delayed in retinopathic hexagons compared to aretinopathic hexagons. Relative amplitude was significantly decreased only in the severe NPDR group in both retinopathic and aretinopathic hexagons. The duration of diabetes and glycemic control status did not correlate with the local mfERG responses. CONCLUSIONS: Local mfERG showed considerable implicit time delays in clinically normal retinal areas that correlated significantly with the severity of diabetic retinopathy of the whole retina. PMID- 17851270 TI - Analysis of the diagnostic value of plasma endothelin for diabetic retinopathy using the receiver operating characteristic curve. AB - AIM: To investigate the diagnostic efficacy and clinical application value of plasma endothelin-1 for diabetic retinopathy using receiver operating characteristic (ROC) curve analysis. METHODS: This was a prospective investigational study. Funduscopy and fundus fluorescein angiography were used as gold standards for the diagnosis of diabetic retinopathy. Plasma endothelin-1 was measured in 96 diabetic patients with retinopathy (the case group) and 144 diabetic patients without retinopathy (the control group). Enumerative data were listed in a fourfold table. The measurement data were analyzed by Student's t test and evaluated by cross-table analysis and ROC curve analysis. RESULTS: (1) The plasma endothelin-1 concentration was higher in the case group than the control group (p = 0.002 < 0.01). (2) If the plasma endothelin-1 level of 162 pg/ml was adopted as the threshold for clinical diagnosis of diabetic retinopathy, the diagnostic sensitivity was 71.2%, diagnostic specificity 58% and diagnostic accuracy 66%. The positive predictive value was 69.81% and the negative predictive value 59.46%, and the positive likelihood ratio was 1.69 and the negative likelihood ratio 0.50. (3) When plasma endothelin-1 was used as a diagnostic criterion for diabetic retinopathy, the area under the ROC curve was 0.737. CONCLUSIONS: Plasma endothelin-1 plays an important role in the development and progression of diabetic retinopathy. When 162 pg/ml of plasma endothelin-1 was adopted as the diagnostic threshold, the diagnostic accuracy was medium; hence, the plasma endothelin-1 level can be used as the first step for diabetic retinopathy screening. PMID- 17851271 TI - Diabetic retinopathy and IGF-1 gene polymorphic cytosine-adenine repeats in a Southern Indian cohort. AB - BACKGROUND/AIMS: Growth factors have been implicated in the pathogenesis of diabetic retinopathy (DR). IGF-1 is known to trigger a critical cascade of molecular events that initiate retinal angiogenesis. Increased vitreous IGF-1 levels have been correlated with the severity of ischemia-associated diabetic retinal neovascularization. In the present study, a cytosine-adenine (CA)(n) repeat in the promoter of the IGF-1 gene is studied for association with DR. METHODS: A total of 127 patients with retinopathy (cases: DR+) and 81 patients without retinopathy (controls: DR-) who had type 2 diabetes were recruited for the study. Patients underwent detailed clinical examination and DR was graded based on stereoscopic digital fundus photographs. Frequencies of alleles and genotypes between the two groups were analyzed for significance using relevant statistical tests. (CA)(17) and (CA)(18) repeats were the more frequent alleles. RESULTS: The frequency of the 18-repeat genotype was significantly higher in DR+ patients when compared to DR- patients and found to confer a 2.4 times (95% CI: 1.2-5.0) and 2.8 times (95% CI: 1.1-7.5) higher risk for developing DR and proliferative DR, respectively, when compared to <18-repeat genotypes. CONCLUSIONS: Our study suggests that the 18-repeat genotype is a susceptibility genotype for DR and its clinical severity in a Southern Indian cohort. PMID- 17851272 TI - Daptomycin does not exert immunomodulatory effects in an experimental endotoxin model of human whole blood. AB - BACKGROUND: Recent studies have shown that distinct classes of antimicrobial agents might exert immunomodulatory effects in experimental settings. Daptomycin is the first member of the class of cyclic lipopeptide antibiotics, which exert their antimicrobial activity via a unique mode of action on the bacterial cytoplasmic membrane. Thus, we tested its ability to influence pro-inflammatory cytokines by use of an established experimental model of human endotoxemia. METHODS: A controlled experimental study design with 4 parallel groups was used. Whole blood from 10 healthy male volunteers was incubated either with saline (negative control), daptomycin (40 microg/ml, control), lipopolysaccharide (LPS; 50 pg/ml, positive control), or the combination of daptomycin plus LPS for 4 h. Real-time polymerase chain reaction was utilized for the measurement of selected pro-inflammatory cytokines, namely IL-1 beta, IL-6 (high sensitivity) and TNF alpha on the mRNA level. Protein concentrations of these respective cytokines were measured in the supernatant using a commercially available ELISA. RESULTS: Incubation of whole blood with LPS significantly increased protein and mRNA levels of cytokines compared to baseline (p < 0.05). However, the combination of daptomycin plus LPS did not exert any significant effect on mRNA and protein levels of IL-1 beta, IL-6 (high sensitivity) and TNF-alpha after 2 and 4 h of incubation compared to LPS incubation alone. CONCLUSION: Daptomycin does not affect pro-inflammatory cytokines in the early phase of endotoxemia. This is most likely due to the unique mode of action of daptomycin, its low potential to penetrate into human cells and its high affinity to bacterial cytoplasmic membranes. PMID- 17851273 TI - Penetration of pollen proteins into the skin. AB - Atopic dermatitis is a chronic remittent skin disease. In the extrinsic form of atopic dermatitis, type IgE-mediated reactions play an important pathophysiological role. The aim of the present study was to examine whether type I allergens can penetrate into the skin. Therefore, pollen proteins were labeled with fluorescein isothiocyanate (FITC), and their penetration profile was studied qualitatively. Solutions of FITC-labeled pollen proteins were applied in vitro on porcine skin and in vivo on human skin. In vitro, the FITC-labeled proteins were observed within the complete stratum corneum (SC) and inside the hair follicles even 15 min after application. They were also distributed inside the dermis around the hair follicles. In vivo, a similar pattern of distribution within the SC and the hair follicles was observed. These results indicate penetration via the SC lipid layers and a faster penetration via the hair follicles. The FITC labeled proteins entered the dermis via the follicular pathway. Therefore, the follicular penetration should be considered in the development of skin protection strategies. To evaluate such strategies, the developed method can be used, and further studies in atopic dermatitis patients are necessary to determine whether the penetration of type I allergens is increased. PMID- 17851274 TI - Skin viscoelasticity displays site- and age-dependent angular anisotropy. AB - One of the dominant characteristics of skin aging is loss of elasticity. Although the changes in the mechanical properties of the skin over several decades of life are substantial, objective measurements have failed to capture their magnitude thus far. Moreover, the mechanical properties of the skin are not uniform in all directions, and there is a need to understand this angular anisotropy. In this work we present a methodology of documenting the angular anisotropy of skin elasticity with high sensitivity and dynamic range using the Reviscometer RVM 600 (Courage & Khazaka Electronic GmbH, Cologne, Germany). The method is based on determining the directional dependence of the speed of an acoustic shear wave on the skin surface at intervals of 3 degrees . Based on the angular distribution of the resonance running time, we define two parameters: the anisotropy and the angular dispersion width. We find that with increasing age the anisotropy increases, while the angular dispersion width decreases. The ratio of these values provides a sensitive parameter for the assessment of the directional behavior of the skin mechanical properties. This parameter provides a large effective dynamic range capable of demonstrating close to an order of magnitude differences in skin viscoelasticity from infants up to adults 75 years of age. Furthermore, we show that the direction of the angular anisotropy relates to the direction of the dermal cleavage lines as defined by Langer, indicating that the anisotropy of the mechanical properties of skin stems from structural parameters. Based on these results, we conclude that the proposed methodology is able to capture accurately the age-dependent changes of the mechanical properties of the skin and to demonstrate a structure-function relationship. PMID- 17851275 TI - Intermittent pressure decreases human keratinocyte proliferation in vitro. AB - BACKGROUND: The aim of this study was to investigate the correlation between pressure changes and keratinocyte proliferation by determining whether keratinocytes exposed to altered mechanical pressures would proliferate at different rates compared to control cells not subjected to pressure changes. METHODS: Tissue culture flasks of human keratinocytes plated at an approximate density of 15,000 cells/cm(2) undergoing an intermittent cyclic pressure of 362 mm Hg at a frequency of 2.28 or 5.16 cycles/min (0.038 or 0.086 Hz) for 8 h were compared to control flasks grown at ambient room pressure. An in-line pressure transducer was used to monitor and adjust pressure within the cell chambers, using a solenoid valve. A thymidine incorporation assay assessed the amount of cell proliferation in each set of experiments. RESULTS: Differences in proliferation between keratinocytes subjected to cyclic pressure changes and control cells were found to be statistically significant (p < 0.05) in 4 out of 5 proliferation assays. Also, a higher frequency of pressure changes consistently generated a reduced proliferation rate compared to that seen in cells exposed to a lower frequency of pressure changes. CONCLUSION: These data indicate that keratinocytes undergoing intermittent pressure changes exhibit decreased proliferation rates compared to controls. Furthermore, an increased frequency rate seems to have a greater effect on proliferation than low-frequency rate pressure changes, suggesting that the stress caused by frequently changed pressure may play a greater role in reducing keratinocyte proliferation than the actual magnitude of load applied to the cells. Our results support the current treatment protocol of reducing speed and duration of walking on the site of the wound to promote healing of foot ulcers. PMID- 17851276 TI - Rising prostate-specific antigen after primary treatment of prostate cancer: sequential hormone manipulation. AB - OBJECTIVE: To evaluate systematically the current endocrine treatment options for patients with biochemical recurrence after radical prostatectomy or radiation therapy for localized prostate cancer. METHODS: Literature search of PubMed documented publications and abstracts from international meetings. Key items included timing and type of salvage hormone therapy, length of its application and handling of side effects. RESULTS: The majority of patients with isolated prostate-specific antigen (PSA) relapse are not candidates for salvage treatment with curative intent. The PSA threshold that triggers initiation of hormonal therapy is debatable and should be based also on pretreatment risk assessment. Intermittent androgen suppression is an emerging concept to circumvent the unresolved controversy of early versus deferred endocrine therapy. Since the tumor load at time of recurrence is low, peripheral androgen blockade with an antiandrogen and a 5alpha-reductase inhibitor is an acceptable first choice. In case of progression, addition of a LHRH analogue would be the next step. Antiandrogen withdrawal and second-line antiandrogens are clinically of limited value. CONCLUSIONS: Biochemical-only progression after definitive treatment in curative intent is different from objective or even symptomatic relapse and allows for sequential hormonal therapy with a variety of compounds. PMID- 17851277 TI - Surgical implantation of the new FlowSecure artificial urinary sphincter in the female bladder neck. AB - OBJECTIVE: To report implantation of the new FlowSecure artificial urinary sphincter with conditional occlusion in a female bladder neck, describe surgical technique and suggest minor modifications to accommodate the device for universal female implantation. PATIENT AND METHODS: A spina bifida female patient with urodynamically proven stress incontinence due to sphincteric incompetence associated to atonic detrusor was implanted with the new artificial sphincter. Operating time was one and a half hours. The cuff was adjusted to the bladder neck with no problems. Excess belt removed from the cuff was preserved and used for loose fixation of tubing and reservoirs in the right paravesical space. The control pump was placed in the right labia. The prosthesis was implanted at atmospheric pressure zero. RESULTS: The device was easily implanted. There were no perioperative complications. Catheter was removed 24 h post-implantation and patient achieved immediate total continence. There was no need for device pressurization at subsequent follow-up. The patient needed intermittent self catheterization for emptying her bladder because of impaired detrusor contractility. CONCLUSIONS: Despite that the new FlowSecure artificial urinary sphincter has only been used for bulbar urethral implantation, we have successfully implanted the device in a female bladder neck with excellent clinical results. Cuff lengthening and connecting tubes shortening would probably enable all female patients to be suitable for implantation. To the best of our knowledge, this is the first time the device has been implanted in a bladder neck. PMID- 17851278 TI - Clinical significance of platelet count in patients with renal cell carcinoma. AB - INTRODUCTION: During the last decades numerous prognostic factors have been studied for predicting survival of renal cell carcinoma (RCC). Platelet count has previously been reported to correlate with prognosis in RCC. The aim of the this study was to evaluate the significance of thrombocytosis in determining prognosis in patients with localized RCC who underwent radical nephrectomy. PATIENTS AND METHODS: The study included 118 consecutive patients. Patients were divided into a normal platelet count group (group 1) and a thrombocytosis group (group 2) according to the preoperative platelet count. Thrombocytosis was defined as a platelet count greater than 400,000/microl. The data about stage distribution, grade, tumor size, histological subtype, hemoglobin level, Body Mass Index (BMI), age, ECOG score, gender, and survival rate of tumors between these two groups were compared. Survival estimates were compared with the Kaplan-Meier method and multivariate analysis was performed using a Cox model. RESULTS: The mean age of the patients was 61.4 years (range 30-78), and the mean follow-up period was 52.7 +/- 19.6 months (range 9-96). Thrombocytosis was present in 23 patients (19.49%). Fourteen (60.86%) of 23 patients with thrombocytosis died of disease progression. Patients with thrombocytosis had a worse prognosis than patients without thrombocytosis (p = 0.001). Thrombocytosis was noted in 8 (10.81%) of 74 patients with stage pT1-pT2 disease and in 15 (34.09%) of 44 patients with stage pT3-pT4 disease (p = 0.004). In univariate analysis, platelet count was correlated with T stage, hemoglobin level, lymph node positivity, ECOG score, and tumor size. Controlling for established prognostic indicators of pathologic stage, tumor size, platelet count, and lymph positivity using Cox's regression test, the difference in survival between the groups remained significant (p < 0.05). CONCLUSION: The platelet count can be considered a useful prognostic factor in patients with RCC who undergo radical nephrectomy. PMID- 17851279 TI - Does age affect the prognosis of patients with testicular germ cell tumor? AB - INTRODUCTION: In this study, the effect of age on the prognosis of testicular germ cell tumors in patients over 40 was investigated. MATERIALS AND METHODS: Ninety-three patients with testicular germ cell tumor who were 40 years old and over were identified in our germ cell tumor database. Patients were grouped according to their age with those between 40 and 44, 45 and 49 and 50 and over constituting groups I, II and III, respectively. RESULTS: Only 15% of the patients of group III had localized disease (p = 0.002). Group III patients had a significantly lower response rate to initial chemotherapy and a higher disease progression rate during therapy (complete response rate: 33.3%, progression rate: 44.4%, p = 0.035). The multivariate analysis revealed that advanced stage was the only independent prognostic factor for survival (p = 0.0011). CONCLUSION: Testicular germ cell tumor patients over 50 years old presented with a more advanced stage and had higher disease progression and disease mortality rates. PMID- 17851280 TI - Clinical predictors of stone fragmentation using slow-rate shock wave lithotripsy. AB - AIM: To determine efficacy and clinical predictors of stone fragmentation when using slow-rate shock wave lithotripsy (SWL). PATIENTS AND METHODS: In total, 116 patients with radiopaque urinary tract stones were randomized into two groups: 57 patients were treated with SWL at 90 shocks/min, and 59 patients were treated with SWL at 120 shocks/min. The efficacy of SWL was evaluated within 1 month after treatment. Patient characteristics, features of stones, and SWL conditions were reviewed. Success rates relating to individual parameters were assessed by using chi-square and Student t tests. All factors were further entered into multivariate logistic regression analysis. RESULTS: There were no statistically significant differences between the two groups with regard to age, sex, site and size of the stones, renal function, and total number of shock waves. In univariate analysis, the success rate was significantly related to shock wave frequency (p = 0.023), length and width of the stones (p < 0.001), total number of shock waves (p = 0.047), and age (p = 0.049). In multivariate analysis, however, only shock wave rate and stone length remained statistically significant (p = 0.021 and p = 0.046, respectively). The overall success rate was significantly higher in the group treated with 90 shocks/min (p = 0.02). However, this higher success rate was statistically significant only in patients with a stone length > or = 10 mm (50.0 vs. 18.5%, p = 0.019). CONCLUSION: SWL at 90 shocks/min yielded better outcomes than SWL at 120 shocks/min, particularly in patients with stone lengths > or = 10 mm. PMID- 17851281 TI - Does lower-pole caliceal anatomy predict stone clearance after shock wave lithotripsy for primary lower-pole nephrolithiasis? AB - AIM: In order to have an idea about the success rates after extracorporeal shock wave lithotripsy (SWL) in patients with lower-pole stones, we reviewed the caliceal anatomy of the patients treated in our clinic. PATIENTS AND METHODS: One hundred and ninety-eight patients having at least a 3-month follow-up period, with a single stone located in the lower pole, were included. Lower infundibulopelvic angle (LIP-A), infundibular width, and infundibular length were measured from standard intravenous urograms taken before initial ESWL. RESULTS: One hundred and thirty patients (65%) were male, and 68 patients (35%) were female. We found no impact of age, sex, and affected side on the results of ESWL. The overall stone-free rate was 61.1% after 3 months of follow-up. The stone-free rates were 47.8 and 81.4% in patients with an acute (< 70 degrees) and an obtuse (> or = 70 degrees) LIP-A, respectively (p = 0.007). Taking the infundibular width into consideration, the stone-free rates were 85.4 and 43.2% for favorable and unfavorable angles and widths (p = 0.003). However, infundibular length and stone sizes were not found to have important effects on a stone-free status (p = 0.546 and p = 0.283). CONCLUSION: We conclude that LIP-A (> or = 70 degrees) has the greatest impact on the clearance of residual fragments produced by SWL. PMID- 17851282 TI - Factors affecting renal scar development in children with spina bifida. AB - BACKGROUND/AIMS: Prevention of renal scarring is the main therapeutic goal in children with spina bifida. We aimed to determine factors affecting renal scar development in these patients. MATERIALS AND METHODS: Records of 312 children admitted between 1994 and 2005 with spina bifida were reviewed. Age on admission, gender, presence of previous febrile urinary tract infections (UTIs), vesicoureteral reflux (VUR), and initial urodynamic findings were noted. Patients were grouped regarding presence/absence of renal scars on DMSA scans. Chi2 and Student's t tests were used for statistical evaluation. RESULTS: Seventy-two patients had renal scars on admission. Mean age was 4.62 +/- 4.59 years for patients without renal scars and 6.35 +/- 4.9 years for patients with scars. Male/female ratio was 1:1 in the scarless group and 1:2 in the group with scars. Previous febrile UTI was present in 11 of 240 scarless patients in contrast to 7 out of 72 patients in the scar group (p > 0.05). VUR was present in only 16.3% of cases without scars, whereas 36.1% of patients in the scar group had VUR. Detrusor overactivity and detrusor sphincter dyssynergia were observed in 67.1% of scarred patients, whereas this figure was 42.4% in the scarless group. The comparison of age on admission, gender, detrusor overactivity, and detrusor sphincter dyssynergia revealed significant differences between patients with and without renal scars. CONCLUSIONS: Late referral, female gender, overactive detrusor, and detrusor sphincter dyssynergia have detrimental effects on renal parenchymal function in spina bifida patients. Patient selection for aggressive treatment using these features may prevent renal parenchymal deterioration. PMID- 17851283 TI - Retroperitoneoscopic nephrectomy for autosomal dominant polycystic kidney disease: initial experience. AB - INTRODUCTION: Nephrectomy for autosomal dominant polycystic kidney disease (ADPKD) has been reported to have significant morbidity and mortality. Because of the large kidney size, laparoscopic nephrectomy is technically demanding and there have been only few reports on this subject. We describe our retroperitoneoscopic technique and review the literature. METHODS: Retroperitoneoscopic nephrectomy was performed in 2 patients. A four-port retroperitoneal access was used, after hilar control the kidney was freed and extracted. RESULTS: The mean operative time was 155 min, the mean intraoperative blood loss was 125 ml. There were no intraoperative complications. A postoperative retroperitoneal hematoma in 1 of the patients was managed conservatively with transfusion. CONCLUSION: Retroperitoneoscopic nephrectomy for ADPKD is feasible. The main advantages of this technique compared to transperitoneal laparoscopy are the quick and easy access to the hilar vessels even in large polycystic kidneys and the strict extraperitoneal route. PMID- 17851284 TI - Laparoscopic treatment of simultaneous tumors in the liver and kidney. AB - BACKGROUND/AIMS: To report our experience with laparoscopic treatment of liver tumors during right-sided transperitoneal laparoscopic nephrectomy. METHODS: Two patients undergoing transperitoneal laparoscopic radical nephrectomy on the right side each had a concomitant tumor in the right lobe of the liver. The first patient was incidentally found to have a lesion suspicious for metastatic disease. The second had a known asymptomatic giant hemangioma of the liver. RESULTS: Total operative time was 130 and 101 min. Estimated blood loss was 400 and 300 ml. There were no complications. The first patient had bilateral papillary renal cell carcinoma and concomitant fibroadipose tissue within the liver. The second patient presented with clear cell carcinoma of the right kidney and a cavernous hemangioma of the liver. CONCLUSIONS: When indicated, simultaneous right-sided kidney and liver tumors may be treated by a combined laparoscopic transperitoneal approach. Laparoscopic expertise is advised. PMID- 17851285 TI - Metastasectomy without systemic therapy in metastatic renal cell carcinoma: comparison with conservative treatment. AB - AIM: The objective of this study was to evaluate the efficacy of metastasectomy after nephrectomy in patients with metastatic renal cell carcinoma who had not received systemic therapy. PATIENTS AND METHODS: A total of 62 patients were included in the study. The patients were categorized according to their surgical treatment: the metastasectomy group (n = 21) and the nonmetastasectomy group (n = 41). RESULTS: In the metastasectomy group, the median overall survival was 36.5 (range 4.0-182.7) months, whereas the patients of the nonmetastasectomy group reached a median overall survival of 8.4 (range 0.9-63.7) months (p < 0.001). The 1-, 3-, and 5-year overall survival rates were calculated at 71.4 and 34.1%, 47.6 and 9.8%, and 9.8 and 2.4%, respectively (p < 0.001). When the patients were stratified according to their characteristics, the overall survival was lower in the nonmetastasectomy group than in the metastasectomy group in the younger patients (p = 0.002), in both male (p = 0.001) and female (p = 0.030) patients, in patients with a poor performance status (p = 0.027), in patients with a shorter time between diagnosis of the primary tumor and development of metastases (p < 0.001), and in patients with a solitary metastasis (p = 0.005). Multivariate analysis using the Cox proportional hazards model showed that only the metastasectomy status was an independent predictor of the overall survival (Hazard ratio 2.57, 95% confidence interval 1.21-5.44; p = 0.014). CONCLUSION: Our findings suggest that for the management of metastatic renal cell carcinoma, complete surgical resection of the metastatic lesions may prolong survival even in patients with some poor prognostic factors who cannot or are not willing to receive systemic therapy. PMID- 17851286 TI - Is antegrade endopyelotomy really less invasive than open pyeloplasty? AB - OBJECTIVE: We investigated the invasiveness of antegrade endopyelotomy and open pyeloplasty in two consecutive series of patients with ureteropelvic junction obstruction. PATIENTS AND METHODS: 98 patients were treated by open pyeloplasty from 1980 to 1991, and 137 patients by antegrade endopyelotomy from 1991 to 1999. Diagnosis of ureteropelvic junction obstruction was made by excretory urogram and/or antegrade pyelography, diuretic renography and retrograde pyelography. Invasiveness was evaluated by the postoperative need for analgesics, the complication rate and the residual long-term symptoms after surgery. RESULTS: The postoperative need for opiate analgesics was significantly higher in patients after open pyeloplasty than after antegrade endopyelotomy. Ten percent of the patients complained of problems with the lumbotomy scar after open pyeloplasty, which was not encountered after endopyelotomy. Complications after open pyeloplasty occurred in 24% and were more severe than the 11% seen after endopyelotomy. The primary success rate after open pyeloplasty was 98 and 89% after antegrade endopyelotomy. The long-term success rate, > or = 24 month postoperatively, was 96% (median follow-up 37 (24-196) months) and 76% (median follow-up 32 (24-73) months), respectively. CONCLUSION: Open pyeloplasty and endopyelotomy both have a high success rate with better patency results after open pyeloplasty. Open pyeloplasty is more invasive and has a higher morbidity. Endopyelotomy is a minimally invasive procedure with faster recovery, fewer and minor complications, significantly less need for peri- and postoperative analgesics, less residual pain due to the access, and no functional and esthetic sequelae of lumbotomy. PMID- 17851287 TI - Elucidation of the mechanism of crystal-cell interaction using fibronectin overexpressing Madin-Darby canine kidney cells. AB - INTRODUCTION: Attachment of newly formed crystals to renal epithelial cells is considered to be a critical step in stone formation. Previously, we reported that exogenous fibronectin (FN; 220-240 kDa) had an inhibitory effect against renal tubular cell injury in Madin-Darby canine kidney (MDCK) cells. However, the exact mechanism of FN is not fully understood. To examine the role of FN in crystal cell interaction, we generated stably transfected MDCK cells that overexpress FN. MATERIALS AND METHODS: MDCK cells were transfected with rat FN cDNA. First, we assessed cell injury by addition of calcium oxalate monohydrate (COM) crystals. Next, we examined the effect of FN on the adhesion of COM crystals. Finally, we studied the association of COM crystals by scanning electron microscopy. RESULTS: Cell injury was significantly reduced in the transfected cells relative to control MDCK cells. In the inhibitory assay, crystal adhesion decreased markedly as compared with control MDCK cells. Morphological study showed that few crystals were attached to the surface of the transfected cells. CONCLUSIONS: We elucidated the relationship between crystal-cell interaction and FN by using FN overexpressing MDCK cells. We suppose that FN inhibits the adhesion of crystals to cells by coating the renal tubular epithelial cells. PMID- 17851288 TI - Heterogeneous p27(Kip1) expression within primary renal cell cancers, their invasive margins and peritumoral renal parenchyma correlation with pathological and prognostic features. AB - INTRODUCTION: The expression of the negative cell cycle regulator p27(Kip1) is frequently found to be deregulated in various human cancer types. Whether expression of p27(Kip1) can be used as prognostically relevant biological variables for renal cell cancer patients still remains to be clarified. Therefore, in the present investigation the expression within different tissue areas obtained from renal cell carcinomas was determined. PATIENTS AND METHODS: For analysis of p27(Kip1) in 420 tumor nephrectomy specimens obtained from 420 consecutively included patients, tissue microarrays were used comprising of 1,260 tissue samples each obtained from the tumor itself, the invasive front as well as non-malignant surrounding parenchyma. A sufficient follow-up after surgical therapy was available in 251 cases. RESULTS: In univariate survival analysis, decreased expression of p27(Kip1) within tissue cores obtained from the invasion front was significantly correlated with the patients' disease-specific long-term survival (p = 0.02, log-rank test). In contrast, expression of p27(Kip1) protein within the primary tumors was not identified to reveal any prognostically important information. In Cox regression analysis, histological stage and grade (p < 0.01), the presence of regional lymph node (p < 0.01) or distant metastases at the time of surgery (p < 0.01) as well as decreased expression of p27(Kip1) (p = 0.04) within the invasion front tissue samples independently predicted the disease-specific long-term survival following surgery. CONCLUSION: Our analysis demonstrated that p27(Kip1) is heterogeneously expressed in renal cell carcinomas. Moreover, the result of the present study supports the prognostic value of p27(Kip1) protein expression for patients diagnosed with renal cell carcinoma. PMID- 17851289 TI - Altered regulation of renin-angiotensin, endothelin and natriuretic peptide systems in rat kidney with chronic unilateral ureteral obstruction. AB - BACKGROUND: The present study was designed to investigate the role of the local renin-angiotensin-aldosterone system (RAAS), endothelin (ET) and the natriuretic peptide system (NPS) for the development of renal fibrosis and progressive renal disease in experimental unilateral ureteral obstructed (UUO) rats. METHODS: Male Sprague-Dawley rats (180-200 g) were unilaterally obstructed by ligation of the proximal ureters for 14 days. Control rats were treated in the same way, except that no ligature was made. The mRNA expressions of local renin-angiotensin system, aldosterone synthase (CYP11B2), ET-1 and NPS was determined in the cortex by real-time polymerase chain reaction. RESULTS: Following the unilateral ureteral obstruction, the mRNA expressions of angiotensin-converting enzyme 1, ET 1 and transforming growth factor-beta1 (TGF-beta1) were increased, while angiotensin-converting enzyme 2 was decreased in the obstructed kidney compared with the controls. Angiotensin II type 1 receptor was decreased and TGF-beta1 was not changed in contralateral kidney compared with the controls. Atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide expressions were increased in UUO kidneys compared with the controls, while natriuretic peptide receptor-A was decreased in UUO kidneys. CONCLUSION: The local RAAS and ET-1 was upregulated which may play a role in the progressive renal fibrosis in obstructed kidneys in rats with UUO. The enhanced activity of NPS in UUO kidney may play a role to compensate against progressive renal fibrosis in chronic obstructive uropathy. PMID- 17851290 TI - Cytomegalovirus and Clostridium difficile ischemic colitis in a renal transplant recipient: a lethal complication of anti-rejection therapy? AB - Intestinal ischemia is reported to be the most common gastrointestinal complication of renal transplantation and a potential cause of morbidity and mortality. The recent use of more potent immunosuppressive drug regimens has reduced the incidence of acute rejection, increasing the incidence of potentially fatal infectious complications, such as clinically important cytomegalovirus (CMV) infection. A 42-year-old kidney transplant recipient experienced on postoperative day 10 a dehiscence of the ureterovesical anastomosis, associated with a 7-cm longitudinal tear graft on the lower pole of the kidney and an ureteral ischemia. A graft biopsy demonstrated a mild acute rejection for which the patient received an unsuccessful administration of steroids, with progression of the rejection, so that 1 mg/kg/day antithymocyte globulin was administered. Two days later the patient presented with fever (39.5 degrees C), diffuse abdominal pain with tenderness and bloody diarrhea, and diagnosis of CMV colitis was achieved; rectal samples were taken for histologic examination, and Clostridium difficile toxin was isolated. A subtotal colectomy with Hartmann's procedure was performed, but the patient died 13 days later of a multiple organ failure. The risk of lethal CMV colitis is increased in patients being treated with anti-rejection therapy for severe acute rejection; the occurrence of simultaneous infection, such as pseudomembranous colitis, usually characterized by a favorable prognosis, increases the mortality rate in these patients. PMID- 17851291 TI - Bladder stone formation after a tension-free vaginal tape procedure: report on two cases. AB - We present 2 cases of large bladder stones formed on a tension-free vaginal tape (TVT) which was inadvertently passed through the bladder during the continence procedure. The stones together with the intravesical portion of the slings were removed using a suprapubic approach. High clinical suspicion of bladder complications is necessary when evaluating patients with urinary symptoms after a TVT operation. PMID- 17851292 TI - Laparoscopic management of patent urachus in an adult man. AB - A 35-year-old man presented with recurrent urinary discharge from the umbilicus. A diagnosis of persistent patent urachus was established by magnetic resonance imaging. Radical excision of urachal remnant tissue was accomplished by laparoscopic surgery using four ports. Magnetic resonance imaging is diagnostic in urachal remnants. Radical excision of urachal remnants may safely be done by laparoscopic access. PMID- 17851293 TI - Ureteroappendiceal fistula due to gossypiboma. AB - A case of gossypiboma (retained surgical sponge) is described which caused ureteroappendiceal fistula 4 years after an open right ureterolithotomy operation. The patient was treated by removal of the retained sponges, appendectomy and ureteral stent insertion. PMID- 17851294 TI - Is the presence of perineural and perivascular invasion a risk factor for positive surgical margins during neurovascular bundle preservation radical prostatectomy procedure? PMID- 17851296 TI - Optimizing on smoke free legislation making the most of the opportunity. AB - Stop smoking service provision faces significant challenges in optimizing the opportunities raised through the smoke free legislation, which prohibits smoking in a public place. There are a number of innovations in service provision allowing a more tailored and flexible approach to stopping smoking, where the patient requirements are central. Innovations such as cut down then stop (CDTS), combination nicotine replacement therapy (NRT) use, and new drug therapy Champix all provide increased options for the smoker. PMID- 17851297 TI - Blood glucose monitoring: reducing the cost, increasing the benefit. AB - The level of self blood glucose monitoring in patients who have diabetes has escalated over recent years following the results of two main research studies which identified a strong correlation between 'tight' blood glucose control and the reduction in diabetes related complications. This article analyses the effectiveness of self blood glucose monitoring for people with diabetes. Based on the research presented it goes on to discuss which patients should be encouraged to self blood glucose monitor and identify those for whom it may not be beneficial. Self blood glucose monitoring is discussed in relation to those receiving insulin therapy and those on diet and oral medication. Appropriate monitoring regimens are highlighted to ensure the effects of diet and medication on blood glucose level is assessed. Finally, strategies to look for patterns and trends in blood glucose levels are considered. PMID- 17851298 TI - Stoma care nursing: what the community nurse needs to know. AB - The transition from hospital to home can be a worrying period of time for a patient with a newly formed stoma. It is well documented that community care is important, however this transition has been seen as a weak link in the care for a patient with a stoma (Allison 1996). In most cases following discharge from hospital, the nurse specialist in stoma care will visit the patient at home as a means of maintaining continuity of care. It is also important that the patient's GP, district nurse and other relevant community services are introduced to ensure a cohesive approach to the patients care at home (Taylor, 2003). This article therefore aims to offer the community nurse an overview of stoma care nursing in order to provide the continuity of care much needed by this group of patients. PMID- 17851299 TI - Urinary catheterization: selection and clinical management. AB - Urinary catheterization is a common medico-nursing procedure in both acute and primary care. There is a variety of catheters and associated equipment available on prescription in the UK, how do nurses and other healthcare staff ensure that patients are able to access the most appropriate products for their individual needs? This article will look at the common reasons for catheterization and the rationale for the selection procedures in selecting the optimum method of catheterization, equipment selection and management options to ensure best practice for patient care. Different methods of catheterization, intermittent and indwelling, both urethral and suprapubic, will be considered in regard to preventing infection and providing optimum catheter management. PMID- 17851300 TI - Policy update: practice based commissioning in community nursing. AB - This article looks at the importance of practice-based commissioning (PBC) as an activity to determine what care and services are provided to patients and communities. It gives examples of where community nurses are, and could be, involved in the process of PBC, and calls for the provision of information and support to enable nurses to join other practice based commissioners in the developing PBC groups. It acts as a policy update for community nurses. PMID- 17851301 TI - Managing a common dermatological problem: incontinence dermatitis. AB - Incontinence dermatitis is an under-recognized and under-researched problem that mostly affects older people who have continence problems. Nurses who are aware of the risk factors can provide care that reduces the risk of this distressing problem. If incontinence dermatitis occurs, evidence-based care can be used to treat the person and reduce the risks of further complications. PMID- 17851302 TI - Pain relief in osteoarthritis and rheumatoid arthritis: TENS. AB - Pain is a common symptom experienced by people with osteoarthritis and rheumatoid arthritis and impacts upon mobility and quality of life. This article reviews the limited evidence relating to TENS for pain relief which suggests that it is beneficial for some patients and does no harm. More research is needed to clarify optimal treatments regimes and its cost-effectiveness compared to conventional analgesia. PMID- 17851303 TI - Improving engagement with older people. AB - This article seeks to explore how the older person can be involved and informed in making policy at a local level. Their experience and expertise is invaluable and older people are best placed to voice where services are falling down and their needs are not being met. Government needs to engage with the older person much more effectively. PMID- 17851304 TI - Care pathways: a legal sword or shield? AB - District nurses use care pathways to ensure the efficient delivery of evidence based high quality care. However, many health professionals, including district nurses have expressed concern that comparing the actual care delivered with a care pathway makes them more susceptible to litigation should the patient suffer harm during the course of treatment. In this article Richard Griffith considers the legal implications of care pathways. PMID- 17851305 TI - Commissioning for tomorrow's healthcare. PMID- 17851307 TI - Clostridium difficile: dealing with a silent menace. AB - Clostridium difficile infection is a growing problem and infection is not confined to acute hospitals. People with C. difficile may be cared for in community hospitals or at home. Some people with C. difficile suffer recurrent bouts of infection, others are left with ongoing bowel problems as a result of the infection. Prevention, wherever possible, through prudent antibiotic prescribing and scrupulous infection control procedures can reduce infection risks. Prompt diagnosis and treatment can reduce the risks of life threatening colitis or chronic bowel problems. PMID- 17851308 TI - Home enteral feeding: part 2 current issues in community practice. AB - Part 1 provided an overview of enteral tube feeding and management in the community. Due to the limited evidence base there are many aspects of the practical management of patients on home enteral tube feeding (HETF) that has as yet not been standardized, particularly around issues such as the type of syringes and water that should be used in HETF. There are also some areas where the guidelines are clear but difficult to apply in the community (such as with maximum feed 'hanging times') or where further guidance is required (such as for confirming the position of nasogastric tubes in patients on acid-reducing therapy). Finally, as NHS trusts look at further ways to save money, enteral feeding is being increasingly scrutinised and needs to be carefully managed, with the involvement of healthcare professionals who understand patient needs and the commercial HETF market. This article is based on personal views and local discussions about the issues in question and, until further research and national standards are available, are subject to local interpretation. PMID- 17851309 TI - Infection control: worlds apart primary and secondary care. AB - Healthcare associated infection continues to be a major cause of morbidity and mortality in healthcare. The fact that most of what has been written on the subject of infection control and prevention relates to the hospital setting is perhaps understandable given the proximity and immune status of patients in secondary care. However, the change of term from hospital-acquired infection to healthcare-associated infection acknowledges that a similar burden may exist in community settings. Influential reports suggest that community infection control is ill-defined and there is ongoing debate whether community-based infection control nursing involves the same or different approaches to hospital infection nursing. This paper explores some of the differences between infection control practice in primary and secondary care and examines the reasons for this. PMID- 17851310 TI - A call for greater flexibility in the use of public transport. AB - This article, brought to you in association with Help the Aged, looks at the difficulties involved in using public transport for the older person. Help the Aged is calling for a flexible transport system which provides a free bus pass or travel tokens depending on what works for individuals. PMID- 17851311 TI - Actiq: an effective oral treatment for cancer-related breakthrough pain. AB - As a result of improved survival in cancer and the transfer of care from hospital to primary care, community nurses are taking increasing responsibility for the management of patients at all stages of the disease. Persistent or background pain is common, but between 40% and 80% of patients with advanced cancer also experience breakthrough pain (BTP), a sudden, rapidly escalating flare of pain occurring against a background of otherwise well-controlled persistent pain. While background pain can be successfully managed in most patients, BTP presents a particular challenge to community nurses, because short-acting, 'normal release' oral opioid drugs are absorbed too slowly to treat the typical episode. As this article explains, Actiq is an effective strong opioid with a rapid onset and short duration of action that closely matches the characteristics of an episode of BTP. PMID- 17851312 TI - Termination of pregnancy: a case for a change in the law. AB - In recent months there has been renewed public and parliamentary debate on whether the abortion law in the United Kingdom should be reformed. Parliament has debated the issue on three occasions and now the House of Commons Select Committee on Science and Technology are calling for evidence in support of their inquiry into reform of the Abortion Act 1967. The inquiry gives district nurses the opportunity to inform the debate and ensure that their voices are heard given that topics for reform include nurse-led abortions and home abortions. In this article Richard Griffith and Cassam Tengnah review the development of the law relating to abortion and highlight the areas of reform to be considered by the select committee. PMID- 17851313 TI - Like children, older people deserve protection. PMID- 17851314 TI - Safer care for acutely ill patients. PMID- 17851315 TI - New challenges and new thinking in sickle screening. PMID- 17851316 TI - Moral dilemmas associated with the withdrawal of artificial hydration. AB - Withholding artificial hydration from unconscious terminally ill patients is a complex phenomenon identified as terminal dehydration. Towards the end of a terminal illness it is acknowledged that a patient's desire for fluid and food diminishes, followed by a period of unconsciousness (McAulay, 2001). Inconsistent care philosophies produce divergent opinions and often diametrically conflicting treatments (Craig, 1994). Additionally, literature disputes the detrimental effects of dehydration; therefore, decisions pivot on legal and ethical considerations. Consequently, the viewpoints of the medical and nursing staff can vary; furthermore, recognition must be made to the psychological impact of the relatives. As terminal illness is boundless, all areas of healthcare can be affected. Further investigation into this dilemma is required to identify the most appropriate care management plan. PMID- 17851317 TI - Spiritual distress and integrity in palliative and non-palliative patients. AB - Twenty-two patients in a Midlands acute hospital Trust supplied recorded narratives of their experience of spiritual distress, their hopes for spiritual integrity, and any means that were proving helpful in moving from distress to integrity. The research subjects included both patients in palliative care and those undergoing various therapies. There was little difference between the responses of these two groups. The most frequently expressed spiritual distress centred on the sense of 'not being myself', and concern for the family. The most frequently expressed spiritual integrities, were the hope to help others, and to use the illness as an opportunity for personal growth and acceptance. Support from hospital staff was seen as most important in facilitating change from distress to integrity. PMID- 17851318 TI - Globalization, commodification and mass transplant of nurses: Part 1. AB - This two-part article examines the mass transplantation of nurses within the context of globalization. Part one focused on the international data regarding the global shortage of nurses, the increase in nurse migration from 'underdeveloped' to 'Western' countries, definitions and descriptions of global health and summarized the debate so far, such as it is. Part two draws attention to how this group of migrating nurses is more often than not comprised disproportionately of women and accordingly, draws on critical feminist ideas to demonstrate how such mass transplantation of nurses adds to the idea of women as a commodity. It then draws attention to other similar examples of the commodification of women and highlights the impacts of the loss of this labour force on the 'exporting' countries. The article concludes by joining with others who have proffered constructive suggestions for addressing this problem. PMID- 17851319 TI - Testicular self-examination: the person with learning difficulties. AB - People with learning disabilities are at just as much risk as the general population are of contracting cancer. Mainstream men's healthcare needs are often neglected and this is also true for men who have learning disabilities. Testicular self-examination (TSE) is seen as an important activity that men should be taught to detect any early changes that may be signs of physiological significance. While testicular cancer is rare, its incidence is rising. In the majority of cases of testicular cancer, over 90% are curable (Cancer Research UK, 2002). TSE, for the purposes of this article, is seen as an activity that can be carried out independently (by the man himself) or with the assistance of another person (for example, carer or partner). This article discusses the importance of TSE and, in particular, with men who have a learning disability. PMID- 17851320 TI - Abuse by care professionals. Part 1: an introduction. AB - It is often the most vulnerable members of society that suffer from the physical, psychological, sexual, financial, neglectful and/or discriminatory maltreatment that characterizes the multifaceted nature of abuse. Individuals dependent on care, whether in the remit of health and social care or educational support, may suffer from abuse at the hands of care professionals. This article introduces a series on abuse with a focus on the various definitions of abuse and the historical and international context of mistreatment. PMID- 17851321 TI - Is nursing still the dominant voice? PMID- 17851322 TI - Evaluating student nurse learning in the clinical skills laboratory. AB - This small study was undertaken at Coventry University as part of a wider Nursing and Midwifery Council (NMC) project to determine whether learning that occurs in the clinical skills laboratories (CSLs) can be counted as practice hours or should remain as theory hours. At Coventry University, 3rd-year student nurses were educated on how to teach drug administration skills. They then delivered this teaching to 1st-year student nurses. Both adult and mental health students were involved in this process. All participants in the study were asked for their views of this learning experience. Mentors in practice were also asked how this learning impacted on the students' performance in placement. The findings identify that students considered this to be a good way to learn because the safe environment of the CSL built up their confidence. Mentors also identified it as useful because students came better prepared to their placement, thereby reducing their workload. PMID- 17851323 TI - Regulatory codes of conduct and the common law. Part 2: confidentiality. AB - In Part One, three aspects of the principles that underpin the law of confidentiality were identified from a review of case law. Public interest(s), public safety and the protection of vulnerable people were identified as producing a matrix whereby health providers could see that the rules relating to confidentiality were viewed by all in society as being of the utmost importance. This article concentrates on the codes of conduct that two regulatory bodies have produced to guide the practice of health professionals. The General Medical Council (GMC) and the Nursing and Midwifery Council (NMC) have codes of conduct that are very similar in their guidance. This is not surprising given that the central importance of confidentiality is reflected at the highest possible levels of judicial and political thinking. PMID- 17851324 TI - Development of family interventions: a 9-month pilot study. AB - This article outlines the introduction and development of a team of like-minded people utilizing family interventions (FIs) in a NHS Trust. FIs can be described as therapy sessions for families of people experiencing psychosis, which involve the family, client and therapist. The sessions focus on key elements, such as engagement and assessment, psycho-education, communication skills, problem solving and relapse prevention. Through this focus, problems are analysed and ultimately the interventions are decided and agreed upon. The analysis of the team utilizing FIs in a NHS Trust raises many questions, identifies problems encountered in its conception and highlights managerial difficulties that occurred when trying to balance caseload demands and something envisaged as resource- and time-hungry. The Trust, however, views FIs as one of the ways of addressing part of the National Institute for Health and Clinical Excellence (2002) guidelines, Schizophrenia: Core Interventions in the Treatment of Schizophrenia in Primary and Secondary Care, and lately, Organising and Delivering Psychological Therapies (Department of Health, 2004), and are keen to improve the quality of the service user and carer experience. PMID- 17851325 TI - Naughty nurses during the Crimean War: BJN over 100 years ago. PMID- 17851326 TI - Real life death: has reality TV gone too far? PMID- 17851327 TI - Informal carers--where is the support? PMID- 17851328 TI - Preventing falls in hospital--time to change step? PMID- 17851329 TI - From Council to the coffee room. PMID- 17851330 TI - Management of intestinal failure and high-output stomas. AB - Intestinal failure and a high faecal output from a stoma or fistula are rare gastrointestinal complications. Intestinal failure occurs when the intestine fails to absorb sufficient fluids and nutrients to maintain life, and can result from bowel resection or malabsorption. The management of these conditions raises many issues which nurses caring for affected patients need to consider. This article will discuss those relating to feeding, appliances and medication. Two methods of feeding that can be useful in patients with intestinal failure, namely parenteral nutrition (intravenous feeding) and fistuloclysis (feeding via an intestinal fistula), will be explored. Finally, a short case study will be presented to highlight the effects of some of these interventions and the problems that they can cause for patients. PMID- 17851331 TI - Assessing the value of silicone and hydrocolloid products in stoma care. AB - Intact skin among many other functions provides a protective barrier between the body and its environment, which is critical in regulating transepidermal water loss (Wilkinson and Moor, 1982). The frequent application and removal of adhesives can damage skin by stripping away the outer epidermal layers. Older people, very young children and those with an underlying skin disorder may be particularly at risk (Gibelli et al, 1999; Lyons and Smith, 2003). Hydrocolloid adhesives, which hold moisture in the adhesive mass, are more skin friendly than the acrylic adhesives they now replace and have now become the material of choice for ostomy flanges and flange extenders (Smith et al, 2007). To understand stoma care nurses' awareness of the value of technologically advanced silicone and hydrocolloid products, the authors undertook a nationwide postal survey. The survey, commissioned by four companies in the United Kingdom, who make silicone and hydrocolloid products that can be used in stoma care, were keen to evaluate the awareness of these products to confirm their importance to the patient and why they should be appropriately categorized for reimbursement by the Department of Health. PMID- 17851332 TI - The impact of preoperative education on postoperative pain. Part 2. AB - The second of this two-part article examines the impact of preoperative education on postoperative anxiety, pain and recovery. The first part (Oshodi, 2007) explored the general concept of preoperative education. Surgery can be physically and psychologically stressful for patients. It is hypothesized that education before surgery reduces anxiety and enhances postoperative outcomes. This article critically reviews some of the published research in this field since 1994 through a rigorous methodology to evaluate the impact of preoperative education on postoperative outcomes. Despite inconsistencies in the evidence, the studies all point to the fact that preoperative education is beneficial to adult surgical patients. Based on the evidence presented, implications for nursing are discussed and recommendations for practice are made. PMID- 17851333 TI - Recognizing and reducing interference on 12-lead electrocardiograms. AB - The 12-lead electrocardiogram (ECG) is a diagnostic test used in many different clinical settings. Healthcare professionals who record ECGs as part of their role are often unable to recognize interference that disrupts the quality of the ECG recording. This interference can lead to a reduction in diagnostic quality. Nurses who record ECGs should be able to recognize the commonly encountered forms of interference, and be able to take steps to eliminate, or substantially reduce, this interference whenever possible to ensure the highest possible quality of ECG recording. PMID- 17851334 TI - Infection control and antiseptic methods: the BJN over 100 years ago. PMID- 17851335 TI - Back to basics: finding an optimal cerumenolytic (earwax solvent). AB - An in vitro study was conducted to assess the effectiveness of the commonly used aqueous and organic cerumenolytic (earwax solvent). Three agents were included in the study: olive oil, sodium bicarbonate and urea-hydrogen peroxide complex 5% in glycerol. Distilled water was used as a control. The disintegration of preformed wax plug was noted at specific intervals. The test tube containing distilled water as a control was found to be most effective and fastest in completely disintegrating the wax. This was closely followed by sodium bicarbonate. In contrast, the organic products, namely urea-hydrogen peroxide complex 5% in glycerol showed very little cerumenolytic effect. Olive oil, the most commonly used solution, was ineffective in disintegrating the wax plug even after 24 hours. The study shows aqueous cerumenolytics are more effective than organic agents. PMID- 17851337 TI - End-of-life issues: common law and the Mental Capacity Act 2005. AB - The preceding articles in this group of the series have thus far identified the common law principles in the sections of the Mental Capacity Act 2005 in respect of certain groups of people--those who retain their capacity to organize their own health-related affairs, those who have lost their capacity to self-determine their health choices on a temporary basis, and those who are no longer competent but who had previously identified their choices in respect of treatments and care. One common theme attaches to these groups--they all fall within the common law principles that underpin the health-related needs of those whose lives are supposed to continue after the decisions have been identified. This article, the last in this group, addresses specifically the legal principles, the ethical and moral dimensions, and the practical aspects of decisions where the consequence will be death--the so called 'end-of-life issues'. PMID- 17851336 TI - The psychological impact of aggression on nursing staff. AB - Aggression and violence towards nursing staff in UK health care is a growing problem. While the National Institute for Health and Clinical Excellence's (NICE, 2005a) guidelines 'The Short-Term Management of Disturbed/Violent Behaviour in In Patient Psychiatric Setting and Emergency Department' offer a way forward in managing aggression for healthcare staff, the psychological impact of aggression remains an area of concern. Post-incident review has been identified as an approach to considering untoward incidents of aggression, yet post-incident support and interventions for staff experiencing the psychological effects of aggression remain inconsistent and curtailed in many areas. This article discusses the care of a nurse who experienced post-traumatic stress disorder as a result of aggression in the workplace. The process of assessment and treatment is presented with underpinning theories of trauma used to illuminate the discussion. Practical use of current recommended treatments of cognitive behavioural therapy and eye movement desensitization and reprocessing is offered as a method of addressing a growing problem in UK health care. PMID- 17851338 TI - A review of maternal nutrition and fetal gene expression. AB - Research suggests that nutrient imbalances during pregnancy may result in alterations in fetal gene expression. A thorough review of the literature appears to identify that maternal dietary intake of B vitamins, choline and methionine may reduce the expression of potentially harmful genes. This short review aims to evaluate how the maternal diet can affect gene expression and explain how this knowledge can be incorporated within the nursing practice to improve the long term health status of the next generation. PMID- 17851340 TI - A written assessment is an invalid test of numeracy skills. AB - Nurses need good clinical numeracy skills to aid them in their clinical practice. There is some concern, however, that the calculation skills learned during pre registration nurse education have little practical application to nurses. This article discusses the Fitness for Practice initiatives from the Nursing and Midwifery Council which aim to ensure new registrants are numerate. The article argues that written numeracy assessment tools are not a valid test of the numeracy skills candidates will require for clinical practice and that nurse education needs to focus on researching and examining how best to support, assess and develop the numeracy skills of nursing students within their clinical practice placements to ensure that at the point of registration they are fit for practice. PMID- 17851339 TI - Nurse-led triage of acute medical admissions: accurate and time-efficient. AB - In many hospitals a variety of triage systems are used by senior medical staff to identify likely length of stay (LOS) of acute medical admissions and thus facilitate a streamlined admission under either acute medicine or general internal medicine (GIM). The authors evaluated if senior nursing staff on the medical assessment unit could triage patients depending on their predicted LOS as accurately as consultant acute physicians. Each of 193 medical admissions were independently triaged by both groups to either acute medicine (<48 hours) or GIM (>48 hours) depending on predicted LOS. The accuracy of patient triage was identical for senior nursing staff and consultants (80.8% vs 81.9%), when 95% confidence intervals are taken into account. Nursing staff triaged patients a mean of 8.5 hours earlier than consultants. This study demonstrates that triage of acute medical admissions is a practical extension of the senior nursing role and has been successfully implemented, with accuracy of nursing triage (83.5%) being maintained in a repeat study 6 months later. PMID- 17851341 TI - My timely view of the profession of nursing today. PMID- 17851343 TI - Gut Week - an important and easily digestible initiative. PMID- 17851344 TI - Parental mental illness: the effects on children and their needs. AB - Parental mental health problems can have a major impact on children and studies indicate that they increase the risk of children developing behavioural, social, emotional and educational problems (Royal College of Psychiatrists, 2004). While this impact has been acknowledged for some time, there appear to be few interventions in the UK to help reduce the effect that parental mental illness has on children. This article discusses the impact of parental mental illness on children and gives examples of interventions that have been found to be useful in other countries. Potential interventions that mental health services in the UK could adopt are also discussed. PMID- 17851345 TI - The petals of recovery in a mental health context. AB - In the last 10 years the concept of recovery has entered the discussion on mental health. Since then it has been surrounded in debate - from advocates who suggest that there is a need to build mental health services on recovery principles, to people who suggest that there is insufficient 'empirical' evidence to support a reorientation of services. The focus of this article is on exploring the concept of recovery as both a process and an approach to care. PMID- 17851347 TI - The problems of being a private nurse: the BJN over 100 years ago. PMID- 17851346 TI - Rectal irrigation in the management of functional bowel disorders: a review. AB - Faecal incontinence and constipation are examples of functional bowel disorders that can lead to distressing psychological and physical symptoms which seriously impact upon quality of life. Rectal irrigation has been introduced as a treatment option for such patients. This article critically reviews and evaluates the current evidence on the effectiveness of rectal irrigation as a management option for functional bowel disorders. The review was conducted using BIOSIS, AHMED, CINAHL, MEDLINE, and Web of Knowledge. From 1051 articles identified through the literacy search, only nine were specifically concerned with the evaluation of rectal irrigation as a treatment option for functional bowel disorders. The results of the literature review do indicate that rectal irrigation could be a successful treatment option for some people, however, variations between studies and methodological limitations mean evidence of the effectiveness of rectal irrigation is lacking. PMID- 17851348 TI - Problems experienced by haemodialysis patients in Greece. AB - Even though Greece has a disproportionate number of haemodialysis stations for the treatment of end-stage renal disease (ESRD), and a rapidly rising number of patients on dialysis, there has been no study of the lived experience of haemodialysis treatment in Greece. ESRD and dialysis drastically impact patients' everyday life, therefore expectations and desires play a major role in adapting to alterations and restrictions. An understanding of these culturally-influenced expectations and desires is essential for the delivery of holistic nursing care. This study aimed to explore how Greek patients receiving long-term haemodialysis perceived their problems and to describe the impact of haemodialysis on their lives. Using a grounded theory approach, 23 patients with ESRD receiving haemodialysis were purposively recruited from two hospital dialysis centres in Athens, Greece. Data were collected during 2006 by personal interviews. Given a distinctive patient experience of haemodialysis, some insight into their common concerns can facilitate provision of healthcare services that adequately meets their needs. By developing an understanding of the experience of renal illness and therapy for a group of people using dialysis, this study was intended as a contribution towards enabling healthcare professionals to provide more effective support to people who are living with this chronic condition. PMID- 17851349 TI - Legal principles of confidentiality and other public interests: Part 1. AB - The principles of confidentiality are of paramount importance to nurses and all health professionals. This is explicitly so as the Common Law recognizes confidentiality and supports its importance. However, current practice must take cognizance of the realities of 21st century healthcare delivery - we live in an age of electronic data that is potentially very difficult to keep secret. New rules, protocols and guidelines are being formulated, and regulatory bodies such as the Nursing and Midwifery Council (NMC) reflect such rules in their codes of professional conduct. There is, however, a debate that is suggesting that the rules that relate to confidentiality may need to expand or even bend a little as innovate ways of obtaining, storing, utilizing and communicating data continue to occupy the minds of government and those who formulate legal principles (British Medical Association, 2005). This series of three articles will explore these issues. The first part is a review of case law that explores the fundamental legal principles that underpin confidentiality. The second will concentrate on a review of the guidelines that are to be found in professional regulatory documentation - the NMC and the General Medical Council as they relate to the legal principles. The third and last part will review and reflect on issues that relate expressly to the implementation of electronic patient records, with a review of appropriate statutory legislation and principles of common law. PMID- 17851350 TI - Globalization, commodification and mass transplant of nurses: Part 1. AB - The world is currently facing a shortage of nurses and this is predicted to worsen as a result of the looming en masse retirement of the so-called 'baby boom' generation. Moreover, this problem is foreseen to be far more pronounced in Western countries where the post-Second World War 'baby-boom' demographic was (and is) most prominent. Data collected by various international organizations illustrates a corresponding recent increase in nurse migration and that such mass transplantation inevitably involves the unidirectional movement of nurses from developing countries to developed Western countries. As a result, this two-part article examines this mass transplantation within the context of globalization. Part one provides compelling international data regarding the global shortage of nurses and the corresponding increase in nurse migration from 'underdeveloped' to 'Western' countries. It then situates the phenomenon in the context of global health and highlights the extent of the debate so far, such as it is. PMID- 17851351 TI - Discharge planning: communication, education and patient participation. AB - For the most part, discharge from hospital is routine and uneventful. However, for a percentage of people, discharge from acute care requires careful planning to ensure continuity of care. This is particularly the case with older patients who have complex medical needs. This literature review reveals that the essential elements for discharge planning are: communication, coordination, education, patient participation and collaboration between medical personnel. Outcomes measures of successful discharge planning include patient satisfaction and quality of life. Smooth and efficient coordination of this process reduces stress and anxiety for the patient, family, nurse, doctor, hospital and community services. PMID- 17851352 TI - Thinking and writing at Masters level: a reflective passage. AB - This article identifies key characteristics of Masters level writing and the underpinning relationship of these characteristics to reflective thought. Classical models of reflective writing are reviewed and their focus on reflection as a progressive process is debated. A linear model of reflection is proposed and its application to reflective writing for Masters level assessments is examined. The classical authors tend to present reflection as a process in which the outcomes of reflection becomes deeper at advanced levels. While this is an appropriate application of the concept of reflection for the traditional academic essay, it might not always be so appropriate for other more applied aspects of thinking and writing particularly in the development of advanced nursing practice. A linear model of reflective writing which offers a more pragmatic perspective on reflection is developed. PMID- 17851353 TI - A patient survey of nursing practice philosophy in 2001 and 2005. AB - The nursing philosophy group at St Bartholomew School of Nursing and the London NHS Trust came together to review the existing nursing philosophy, which had been in place since 1996. A new philosophy was circulated in June 2000 and it was viewed as essential that this document be reviewed regularly in response to patient needs. A patient survey was produced to assess patients' understanding of the philosophy and how it related to their inpatient stay. It was an important management tool, which enabled the development of patient-centred nursing based on real patient experience. The philosophy was updated in 2003 and the patient survey has since been repeated in 2005. Results have been delivered back to the Trust's Nursing Policy Board and action plans have been agreed based on the results of the survey in 2005 within the Trust's shared governance framework. PMID- 17851354 TI - Brown's agenda for the next changes in NHS reform. PMID- 17851356 TI - Nutritional care for older people in hospitals. PMID- 17851357 TI - Pain management: setting up a nurse-led femoral nerve block service. AB - Managing pain following a fractured neck of femur is challenging for a number of reasons. This group of patients are typically older people and frail with multiple co-morbidities and are often on numerous medications. In addition to a hip fracture, they commonly present with acute medical problems. Fractures cause significant pain, which can be difficult to manage safely and effectively with the traditional analgesics. A femoral nerve block has been shown to be a safe and effective preoperative intervention for managing pain in this patient group while they wait for surgery. This article describes how an acute pain team have developed protocols and training to establish a nurse-led service for providing preoperative femoral nerve blocks to patients with fractured neck of femur. PMID- 17851358 TI - The impact of preoperative education on postoperative pain. Part 1. AB - This article, the first of two parts, explores the general concept of preoperative education through a literature review. The relatively complex relationships between the ways people perceive a threatening situation, their levels of anxiety, coping styles and postoperative pain is explored. In dealing with these complex relationships, teaching strategies and forms of presentation of preoperative education are also discussed. The second part will examine the impact of preoperative education on postoperative anxiety, pain and recovery. This will be achieved by analysing the evidence available to provide a rigorous appraisal of the literature. PMID- 17851359 TI - Skin barrier function and the use of emollients in dermatological nursing. AB - Nurses will be observing the skin on a daily basis while caring for their patients. Many may appear to have a dry skin or have a skin disease with dryness being the presenting feature in conditions such as atopic eczema, contact dermatitis (irritant and allergic) psoriasis and the ichthyoses. This article explores the barrier function of the skin, factors which influence skin barrier function and the use of emollients for dry skin and skin conditions. PMID- 17851360 TI - A comparative review of clinical governance arrangements in the UK. AB - This article provides a comparative review of the interpretation and implementation of clinical governance frameworks within the four home countries of the UK--England, Northern Ireland, Scotland and Wales. Clinical governance has become one of most significant and important concepts in modern health care. The article considers the policy background and the many definitions of clinical governance, but specifically compares the various strategic and operational approaches to delivery of clinical governance in different parts of the UK. It is suggested that these variations in approach, by each of the four UK countries, can lead to confusion for healthcare professionals in trying to understand, implement and monitor elements of clinical governance in practice. PMID- 17851361 TI - Assessing the effectiveness of the British Army's mental health service. AB - The Ministry of Defence's commitment to modernizing and improving mental health (MH) care for Armed Forces personnel has resulted in considerable changes to frontline services. The last remaining United Kingdom (UK) military psychiatric hospital closed on 1 April 2004 with the move to a clear, integrated care pathway between primary healthcare, military departments of community mental health (DCMHs) and secondary healthcare. The Army's eight UK DCMHs provide a patient centred, occupational MH service grounded in the military MH philosophy of local, easily accessible, effective treatment (O'Brien, 1998). These MH services have been exposed to significant media interest and this article will attempt to quantify the correct state of affairs through patient, customer and staff satisfaction surveys. Clinical groups in the customer survey recorded a satisfaction rate of 87%, the staff survey 72% and the patient survey 94%. The Army has excellent access to specialist MH support and a common theme emerging in these surveys is the perception that the MH teams provide a high quality of service. The three surveys provide valuable direction to improve patient care and highlight strengths such as 97% of patients receiving appointments compatible with their duties. PMID- 17851362 TI - Osteoporosis: not only in women, but in men too. AB - Osteoporosis is a chronic disease where the nurse specialist can make a significant impact. The osteoporosis nurse specialist has an important role, not only in the prevention and management of osteoporosis but also in the promotion of skeletal health across the public health and social care arenas and in the continuing development of services across primary and secondary care. The scale of the problem in women and the potential role of hormone replacement therapy in the prevention and treatment of osteoporosis has played down the problem of osteoporosis and osteoporotic fractures in men, thus facilitating a negligent attitude. This article summarizes the outcome of a dedicated male osteoporosis clinic, which was started by the lead clinicians in metabolic bone disease and falls and subsequently was run by the osteoporosis nurse specialist. A clinic proforma which can be used as a standard in clinical practice is presented. In addition, an algorithm for the management of men with osteoporosis is discussed. PMID- 17851363 TI - Step-by-step guide to critiquing research. Part 2: Qualitative research. AB - As with a quantitative study, critical analysis of a qualitative study involves an in-depth review of how each step of the research was undertaken. Qualitative and quantitative studies are, however, fundamentally different approaches to research and therefore need to be considered differently with regard to critiquing. The different philosophical underpinnings of the various qualitative research methods generate discrete ways of reasoning and distinct terminology; however, there are also many similarities within these methods. Because of this and its subjective nature, qualitative research it is often regarded as more difficult to critique. Nevertheless, an evidenced-based profession such as nursing cannot accept research at face value, and nurses need to be able to determine the strengths and limitations of qualitative as well as quantitative research studies when reviewing the available literature on a topic. PMID- 17851364 TI - Best interests. An holistic approach: Part 2(b). AB - In the last article principles and guidelines were discussed that related to the ways in which nurses have to work with the best interests of their patients in mind. Where a person is ordinarily capable of consenting to or refusing to consent to, a proposed course of treatment or care but has temporarily lost that capacity, there are certain legal guidelines to follow to ensure that the minimum interventions occur until the person regains their capacity to act in their own interests. However, also highlighted was that that certain people have never attained capacity, or do not yet have capacity or have lost capacity on a permanent basis. For these people, there are legal principles that are incorporated in the Mental Capacity Act and these have to be abided by. This article is dedicated to a review of the situation where, sadly, a person has been assessed as not being legally competent to make their own health decisions. However, where a programme of treatment and care has been clinically proposed, the person refuses to co-operate. The situation of enforced treatment and care is a delicate one. Staff have to be aware of the legal principles that apply, with reference to the Mental Capacity Act. PMID- 17851365 TI - Experiences of children in hospital: BJN 100 years ago. PMID- 17851367 TI - Protecting the vulnerable older person. PMID- 17851366 TI - Renal nursing and the Human Tissue Act 2004. AB - The Human Tissue Act of 2004 was introduced in the UK on 1 September 2006. It replaced all Acts that previously governed the procurement and utilization of tissues, cells and organs. It has promoted changes in requirements predominantly in transplantation settings. Past research has highlighted a shortage of organs for transplantation, particularly in renal donation. The new act hopes to remedy this so that future renal transplantations will occur more frequently, therefore improving choice and quality of life for patients with end stage renal disease. For UK renal nurses, the implementation of the Human Tissue Act 2004 presents challenges requiring adaptations of prior learning with new nursing roles. Recommendations can be made to help during the change process. Kurt Lewin's model of change provides a foundation for the understanding and recognition of change processes that occur in the implementation of individual and organizational change. PMID- 17851368 TI - Psychological and physical care of malodorous fungating wounds. AB - To be given a diagnosis of cancer is devastating, but to develop a malodorous fungating tumour can only serve as a constant reminder of the power this disease has over a person's life. It can have a profound effect on quality of life, and the patient often experiences depression, shame, embarrassment and alteration of body image, sometimes leading to social isolation. A literature review looking at the management of these wounds demonstrated limited clinical research on which to base evidence of the best care and although much is written about the psychological effects, there is little to show that these needs are being met. The aim of this article is to explore if nurses are equipped to care for the psychological problems of these patients and briefly considers the psychological issues the nurses caring for these patients may have. PMID- 17851369 TI - E-learning in wound care: developing pressure ulcer prevention education. AB - Patients with pressure ulcers suffer pain and distress from wounds that can require treatment for many months following discharge from hospital (Havard, 2007). This initial and ongoing treatment accounts for around four per cent of the NHS annual budget (Bennett et al, 2004), therefore pressure ulcer prevention and management is beneficial not only to patients but also the NHS. Education for healthcare professionals is an important factor in the prevention and management of pressure ulcers; however, in the current climate releasing staff to attend study days is becoming difficult. In some locations staff have to travel long distances in order to attend while locally-based study days are poorly attended. Developing e-based learning was seen as a realistic option for nurses working in Trust within a large geographical area. PMID- 17851370 TI - Bioactive dressings: old ideas, new technology. PMID- 17851371 TI - Addressing a deficit: wound care and mental health nursing. AB - This article details the development and implementation of a teaching session introduced to address one of the key clinical skills that mental health nurses require in the practice setting--wound management. The session was introduced to equip a group of final year mental health nursing students with the knowledge, skills and attitudes they will need for practicing in a professional environment. The sessions were evaluated to determine their effectiveness in terms of the students' satisfaction with the teaching process, the clinical value and relevance of the content, and to improve the quality of future clinical skills teaching. PMID- 17851372 TI - A review of the treatment for venous leg ulcers. AB - Venous ulcers, sometimes termed varicose or stasis ulcers, are a consequence of damage to the valves in the veins of the legs, leading to raised venous pressure. They are characterized by a cyclical pattern of healing and recurrence. There is a need to have a thorough assessment of patients with leg ulcers by an appropriately experienced clinician to maximize the chance of healing the ulcer. The main treatment is the application of compression, either in the form of compression bandages or hosiery. Dressings are applied beneath the compression with a view to controlling exudate, comfort and to aid healing. There are a large number of dressing products and types available but the evidence to justify their use is poor. The main treatment for venous ulcers should therefore be the application of compression therapy with a simple, low adherent dressing. PMID- 17851373 TI - Allowing the voice in writing. PMID- 17851374 TI - Palliative care for patients with end-stage renal disease: experiences from Hong Kong. AB - As the number of patients with end-stage renal disease continues to grow in Hong Kong, many are opting to be managed conservatively without dialysis. A new service was initiated in Tuen Mun Hospital in 2004 aimed at offering palliative care to dying patients with renal failure. This paper presents retrospective data reflecting our dealings with patients who decided not to initiate or considered discontinuation of dialysis. In total, 107 patients received palliative care from the inception of the new service in August 2004 until July 2006. The findings illustrate that decisions related to initiation or withdrawal of dialysis are often related to personal beliefs and sentiments. Further exploration using qualitative methodology is recommended. The case history expounds a situation in which the patient cannot participate in decision-making concerning treatment options and offers some exploration of the ethical intricacies involved in treating very sick patients with dialysis therapy. PMID- 17851375 TI - Implementation of SIGN 44 guidelines for managing cancer pain in a community setting. AB - This paper discusses the realistic evaluation of an evolving managed clinical network (MCN) in palliative care. The primary focus of this community-based MCN was to improve cancer patients' pain by implementing clinical guidelines. The methods of evaluation included three case studies which featured interviews with patients, relatives and health professionals involved in their care. The results of the case studies were fed back to the network executive group during focus group interviews. The case studies and focus group interviews were carried out at approximately five-monthly intervals. The model of care being implemented by health professionals was refined by the network executive group following each focus group interview. The context, mechanisms and outcomes which evolved from the evaluation contained some elements of a best practice model for controlling pain for patients with advanced cancer. PMID- 17851376 TI - Treating cancer-related breakthrough pain: the oral transmucosal route. AB - Between 40 and 80% of patients with advanced cancer experience breakthrough pain (BTP), a sudden, rapidly escalating flare of pain occurring against a background of otherwise well-controlled persistent pain. Patients often have up to four episodes of BTP each day, with a typical episode reaching its peak intensity in three to five minutes and lasting about 30 minutes in total. It is essential to provide fast and effective relief since BTP reduces the quality of life of patients and their families, and increases health care costs. The usual approach is to treat BTP with a short-acting, 'normal release' oral opioid, but this is absorbed too slowly to treat the typical episode of BTP. As this article explains, oral transmucosal fentanyl citrate (Actiq) is an effective strong opioid that has a rapid onset and short duration of action that closely matches the characteristics of an episode of BTP. PMID- 17851377 TI - Macmillan nurse facilitators for palliative care: evaluation of a pilot project. AB - AIM: to describe and evaluate the implementation of two Macmillan nurse facilitator posts. METHOD: a case study design was adopted with data collection in two main phases. A range of data collection techniques were used, including interview, questionnaire and observation. Various sampling strategies were adopted for the different data collection methods. The use of multiple sources of data supported the triangulation of evidence in order to increase the strength and rigour of the analysis. FINDINGS: two Macmillan nurse facilitator posts were set up with the overall aims of enhancing the quality of palliative care to patients in the community by mobilising the existing skills and supporting the development of new competencies by community nurses. The Macmillan nurse facilitators have been active in three areas directly linked to community nurses' clinical practice: educational programmes, establishment of a palliative resource nurse network and support of clinical guidelines in nursing and primary care teams. The model of peer facilitation whereby the Macmillan nurse facilitators continue to work as district nurses for part of the week has been highly valued by community nurses. CONCLUSIONS: the single most important factor identified in facilitating successful implementation of these posts has been the 'dual role' nature of the posts. This has been key to acceptance of the posts by a generic workforce. The posts provide an effective model for supporting and enhancing the palliative clinical skills and knowledge of generic community-based staff. PMID- 17851378 TI - The challenge of providing palliative care in the nursing home part II: internal factors. AB - Nursing homes are increasingly becoming the place of care and site of death for growing numbers of frail older people dying of chronic progressive illnesses. Despite this increase, empirical evidence suggests that providing palliative care in nursing homes is replete with challenges. In a previous publication, the authors examined challenges external to the nursing home that influence the provision of palliative care, and which may be beyond the nursing home's control (Wowchuk et al, 2006). This paper reviews the primary internal factors identified in the literature that affect the provision of palliative care and are, to some extent, under the nursing home's control. The internal factors include: i) lack of care provider knowledge about the principles and practices of palliative care; ii) care provider attitudes and beliefs about death and dying; iii) staffing levels and lack of available time for dying residents; iv) lack of physician support; v) lack of privacy for residents and families; vi) families' expectations regarding residents' care; vii) hospitalisation of dying residents. Suggestions for practice, education and research are provided. PMID- 17851379 TI - Health professionals' resistance to euthanasia and assisted suicide: a personal view. AB - This commentary evaluates the motives of health professionals' opposition to the legislation of assisted dying. We argue that there are no rational or justifiable grounds for such opposition in the case of patients who are suffering unbearably and whose request to be helped to die is competent, enduring and voluntary. We then engage in plausible speculation about what other, more hidden motives of health professionals might lead to them reject the legislation of assisted dying. We assert that, while these hidden motives are understandable from a psychological perspective, they also suffocate the self-determination of palliative patients. Therefore, the challenge is for health professionals to reconsider extending their own limits in order to fully support their patients' needs. Finally we discuss the consequences of NOT legalising assisted dying, and conclude that this position might be more detrimental than legalising it. PMID- 17851380 TI - Loss and bereavement: a child's perspective. PMID- 17851381 TI - Assessment and monitoring of nutritional status in patients with advanced cancer: part 1. AB - Using a qualitative approach, this study set out to explore nurses' management of patients with advanced cancer, weight loss and eating-associated problems. Extreme weight loss is commonly seen in patients with incurable solid tumour cancer and, to date, it has proved difficult to manage successfully. Currently, little is known about how nurses (often directly involved in the delivery of palliative care) assess weight loss and nutritional status in everyday practice in order to provide appropriate support. In this study, 14 semi-structured interviews were conducted with nurses from both hospital and community settings. The findings revealed that many nurses did not routinely provide early identification and assessment of nutritional status including weight loss, nor did they continue to monitor the patient's progress or deterioration. Many nurses were reluctant to initiate conversations with cancer patients about weight loss, but instead waited for patients and relatives to raise their concerns. As a result, it is likely that informal assessment may have resulted in the reactive style of nutritional management seen. However, nurses interviewed received limited training, but were keen to learn more about nutritional assessment and management. PMID- 17851382 TI - Caring for patients dying at home from heart failure: a new way of working. AB - This article explores the difficult journey that heart failure patients frequently experience when trying to access palliative care. It describes how a team of Macmillan and heart failure nurse specialists attempted to address the problem using the specialist role to effect change. Individual and group learning needs were identified and addressed while the use of reflective practice and group working helped the nurses to manage and implement change. This project, with management support, empowered the specialist teams to think creatively about nursing practice and improve patient care. It has encouraged working with clinical nurse specialists from other disciplines, thus avoiding a narrowness of outlook. Although this project initially focused on a small number of patients, it has enabled the teams to become established in partnership working; the collaborative approach to providing palliative care for end-stage cardiac failure patients has since continued to grow and flourish. It is hoped that, in the future, further studies can take place to gain more detailed information from patients and their families about how partnership working can continue to meet the needs of this group. PMID- 17851383 TI - A qualitative study assessing mental health issues in two hospices in the UK. AB - This study is a qualitative investigation into the experiences of assessing mental health issues by members of staff from two hospices in the UK. Nine individual interviews were held with doctors and nurses from the two hospices using semi-structured interviews. The research method used was grounded theory and the emerging data were analysed using the computer software Atlas.ti. The analysis was conducted around the four main research questions: 'How is mental health assessed in the hospices?', 'What are the staff members' feelings about doing these assessments?', 'How does assessment information inform clinical practice?' and 'What are the perceived training needs of staff?' The findings show that mental health is, to some extent, being assessed within these two hospices; however, no formal assessment strategy is in place. The majority of staff interviewed had very limited experience and/or training in the field of mental health and expressed a lack of confidence when dealing with mental health related issues. A list of training needs has been identified. On the basis of these findings, recommendations have been made to improve the assessment procedures currently used within these two hospices. PMID- 17851384 TI - A survey of commitment and compassion among nurses in residential aged care. AB - AIM: To assess the views and attitudes of aged care staff providing direct care towards palliative care and to identify their learning needs. DESIGN: Survey design using purposive sampling methods. FINDINGS: Nurses and care assistants (n=222) employed within nine residential aged care facilities in regional Australia completed the survey. The majority had received 'on the job training' and were committed to providing end-of-life care. Differences in the level of confidence to deal with patient/family interactions and manage complex palliative care scenarios were evident between nurses and care assistants (p<0.05). Both nurses and care assistants perceived a need for further education in symptom management and communication, yet their content need differed significantly between groups. CONCLUSIONS: Nurses and care assistants in residential aged care facilities demonstrate commitment to the delivery of palliative care and express a need for increased palliative care competencies. The heterogeneity of roles and educational preparation within the aged care workforce indicate that tailored palliative care education initiatives are required to meet the learning needs of aged care nurses and care assistants, particularly in relation to end-of-life care. These data have implications for skill-mix and model of care development. PMID- 17851385 TI - Coping strategies, emotional outcomes and spiritual quality of life in palliative care nurses. AB - It is in accompanying the dying that palliative care nurses say they find meaning in their work. To further explore this phenomenon, consideration of coping strategies is proposed. The main objective of this correlational study was to describe the association between coping strategies (using a revised version of the COPE scale (Carver et al, 1999)), emotional outcomes (distress and vigour; profile of mood states (POMS)), and spiritual quality of life (using the Functional Assessment of Chronic Illness Therapy - Spiritual Wellbeing Scale (FACIT-sp)). A sample of 120 nurses providing palliative care in acute care hospitals and the community in Quebec was included. Positive reinterpretation (beta=.27; p<.01) and turning to religion (beta=.33; p<.001), two strategies related to meaning-making coping and disengagement (beta=-.19; p<.05), were the best predictors, accounting for 22% of variance of spiritual quality of life. These findings are consistent with recent studies and highlight the importance of meaning-making strategies in psychological adjustment to bereavement for palliative care nurses. PMID- 17851386 TI - Comparison of chemical composition and free radical scavenging ability of glycosidically bound and free volatiles from Bosnian pine (Pinus heldreichii Christ. var. leucodermis). AB - The results obtained show that Bosnian pine is rich in glycosidically bound volatile compounds with strong free radical scavenging properties. Since volatiles can be released from nonvolatile glycoside precursors, these compounds can be considered as a hidden potential source of antioxidant substances and may contribute to the total free radical scavenging ability of Bosnian pine. PMID- 17851387 TI - Modeling of acetylene pyrolysis under steel vacuum carburizing conditions in a tubular flow reactor. AB - In the present work, the pyrolysis of acetylene was studied under steel vacuum carburizing conditions in a tubular flow reactor. The pyrolysis temperature ranged from 650 degrees C to 1050 degrees C. The partial pressure of acetylene in the feed mixture was 10 and 20 mbar, respectively, while the rest of the mixture consisted of nitrogen. The total pressure of the mixture was 1.6 bar. A kinetic mechanism which consists of seven species and nine reactions has been used in the commercial computational fluid dynamics (CFD) software Fluent. The species transport and reaction model of Fluent was used in the simulations. A comparison of simulated and experimental results is presented in this paper. PMID- 17851388 TI - Syntheses and biological activities of 6-aryl-3-(3-hydroxypropyl)-7H-1,2,4 triazolo[3,4-b][1,3,4]thiadiazines. AB - A series of 6-aryl-3-(3-hydroxypropyl)-7H-1,2,4-triazolo[3,4-b][1,3,4] thiadiazines were synthesized by the reaction of 4-amino-3-(3-hydroxypropyl)-5 mercapto-1,2,4-triazole (1) with substituted omega-haloacetophenones. Their structures were confirmed by elemental analysis, IR, 1H-NMR, and 13C-NMR. Tests of plant growth regulating effects showed that the title compounds display remarkable inhibitory activities on the growth of radish and wheat. PMID- 17851389 TI - Effective oxidation of sulfides to sulfoxides with hydrogen peroxide under transition-metal-free conditions. AB - A "green" highly selective oxidation of organic sulfides to the corresponding sulfoxides was developed using hydrogen peroxide and glacial acetic acid under transition metal-free and mild conditions. The oxidation procedure is very simple and the products are easily isolated in excellent yields (90-99%). PMID- 17851390 TI - Mistletonone, a novel antioxidative diarylheptanoid from the branches and leaves of Viscum coloratum. AB - Mistletonone, a novel diarylheptanoid, was isolated from the branches and leaves of Viscum coloratum (Kom.) Nakai (Loranthaceae). It was identified as 1,7-di-(p hydroxyphenyl)-5-hydroxyl-cis-2,3-epoxy-1-one on the basis of spectral evidence. The compound showed significant scavenging effects on hydroxyl radicals and superoxide anion radicals in the direct assay using the electron spin resonance (ESR) technique. PMID- 17851391 TI - Oxidative degradations of the side chain of unsaturated ent-labdanes. Part I. AB - A selective route for the degradation of the unsaturated side chain of ent labdanes has been devised, giving two useful synthons: 2beta-acetoxy-14,15,17 trinor-ent-labdane-8,13- dione (5) and 2beta-acetoxy-14,15-dinor-ent-labd-8(17) en-13-one (7), the use of which for the preparation of terpenylquinone derivatives shall be reported elsewhere. PMID- 17851392 TI - Acylated flavone glycosides from the roots of Saussurea lappa and their antifungal activity. AB - The isolation of four novel acylated flavonoid glycosides from the roots of Saussurea lappa and their identification using a combination of 1D and 2D NMR and mass spectrometry is described. The in vitro antifungal and antibacterial activities of the isolated compounds and their mixture were tested on nine fungal and four bacterial strains, using the microdilution method. The compounds and mixture showed moderate to high antifungal activity against most of the fungi tested, compared to a miconazole standard, while only one compound and the mixture showed antibacterial activity against all strains tested. PMID- 17851393 TI - Synthesis of new 1,3-disubstituted-2,3-dihydro-1H-naphth[1,2e][1,3]oxazines. AB - 1,3-Disubstituted-2,3-dihydro-1H-naphth[1,2-e][1,3]oxazines were prepared through the ring-closure reactions of the aminobenzylnaphthols with substituted aryl- and heteroarylaldehydes. PMID- 17851394 TI - New diterpenoid alkaloids from the roots of Delphinium tiantaishanense. AB - Four new diterpenoid alkaloids: tiantaishansine (1), tiantaishannine (2), tiantaishanmine (3), and tiantaishandine (4) have been isolated from the roots of Delphinium tiantaishan. Their structures were elucidated by chemical evidence and spectral analyses, including ESI-MS, HR-EI-MS, 1D- and 2D-NMR. PMID- 17851395 TI - An efficient synthesis of pyrazolo[3,4-b]quinolin-3-amine and benzo[b][1,8]naphthyridine derivatives. AB - 2-Oxo-4-phenyl-1,2,5,6,7,8-hexahydroquinoline-3-carbonitrile (10) reacted with hydrazine hydrate, phenylisothiocyanate or benzoyl chloride to give derivatives 12, 13 and 15, respectively. The latter two products were treated with hydrazine hydrate to afford pyrozole[3,4-b]quinolines derivatives 14 and 16, respectively. Compound 10 also reacted with acetonitrile dimer or malononitrile dimer to yield benzo[b][1,8]-naphthyridine derivatives. A single crystal X-ray crystallographic analysis was performed on compound 10, confirming its structure. PMID- 17851397 TI - Volatile chemical constituents of Piper aduncum L and Piper gibbilimbum C. DC (Piperaceae) from Papua New Guinea. AB - Exhaustive hydro-distillation of the leaves of Piper aduncum and fruits of Piper gibbilimbum (Piperaceae) afforded colorless and pale orange colored oils in 0.35 and 0.30 % yields, respectively. Detailed chemical analysis by GC/MS indicated the volatile constituents of Piper aduncum to be composed of dill apiole (43.3%), beta-caryophyllene (8.2%), piperitione (6.7%) and alpha-humulene (5.1%), whilst the oil of P. gibbilimbum is dominated by the gibbilimbols A-D (74.2%), with the remaining major constituents being the terpenes camphene (13.6%) and alpha-pinene (6.5%). PMID- 17851396 TI - Phase I and phase II ocular metabolic activities and the role of metabolism in ophthalmic prodrug and codrug design and delivery. AB - While the mammalian eye is seldom considered an organ of drug metabolism, the capacity for biotransformation is present. Compared to the liver, the metabolic capabilities of the eye are minuscule; however, phase I and phase II metabolic activities have been detected in various ocular structures. The careful consideration of ocular tissue metabolic processes within the eye has important implications for controlling the detoxification of therapeutic agents and for providing the potential for site-specific bio-activation of certain drug molecules, thus enabling significant improvements in drug efficacy and the minimization of side-effect from either local or systemic drug delivery to the eye. Knowledge of these processes is important to prodrug and codrug development and to researchers involved in the design, delivery and metabolism of ophthalmic drugs. This present article reviews the progress in ocular prodrug and codrug design and delivery in light of ocular metabolic activities. PMID- 17851398 TI - Functionalisation of artemisinin and its ring-contracted derivatives. AB - Isoxazoline analogues of artemisinin were obtained in low yield and low diastereoselectivity from the 1,3-dipolar cycloaddition of nitrile oxides. Alternatively, starting from the aldehyde 7, a number of transformations--Wittig reaction and reduction, Henry reaction and cyanohydrin formation--were achieved in significantly higher yields. In the cases where a new stereocenter was introduced this occurred diastereoselectively. PMID- 17851399 TI - The synthesis and natural distribution of the major ketone constituents in Echinacea pallida. AB - The first synthesis of a series of ketones naturally occurring in E. pallida is described. The natural distribution of these ketones among different Echinacea species is also reported. PMID- 17851400 TI - N-methyl-(R)-3-(tert-butyl)-sulfinyl-1,4-dihydropyridine: a novel NADH model compound. AB - We have synthesized a novel chiral NADH model compound, N-methyl-(R)-3-(tert butyl)-sulphinyl-1,4-dihydropyridine with high enantioselectivity and used it in the reduction of methyl benzoylformate, producing (S)-methyl mandelate in 95% ee. The absolute structure of its precursor, 3-(tert-butyl)sulfinyl pyridine, was determined by X-ray analysis. PMID- 17851401 TI - Phenolic antioxidants identified by ESI-MS from Yerba mate (Ilex paraguariensis) and green tea (Camelia sinensis) extracts. AB - Aqueous extracts of green yerba mate (Ilex paraguariensis) and green tea (Camellia sinensis) are good sources of phenolic antioxidants, as already described in the literature. The subject of this study were organic extracts from yerba mate, both green and roasted, and from green tea. Their phenolic profiles were characterized by direct infusion electrospray insertion mass spectrometry (ESI-MS) and their free radical scavenging activity was determined by the DPPH assay. Organic extracts containing phenolic antioxidants might be used as natural antioxidants by the food industry, replacing the synthetic phenolic additives used nowadays. Ethanolic and aqueous extracts from green yerba mate, roasted yerba mate and green tea showed excellent DPPH scavenging activity (>89%). The ether extracts from green and roasted yerba mate displayed a weak scavenging activity, different from the behavior observed for the green tea ether extract. The main phenolic compounds identified in green yerba mate water and ethanolic extracts were: caffeic acid, quinic acid, caffeoyl glucose, caffeoylquinic acid, feruloylquinic acid, dicaffeoylquinic acid and rutin. After the roasting process two new compounds were formed: caffeoylshikimic acid and dicaffeoylshikimic acid. The ethanolic extracts from yerba mate, both roasted and green, with lower content of phenolic compounds (3.80 and 2.83 mg/mL) presented high antioxidant activity and even at very low phenolic concentrations, ether extract from GT (0.07 mg/mL) inhibited DPPH over 90%. PMID- 17851402 TI - N,N'-ethylene-bis(benzoylacetoniminato) copper (II), Cu(C22H22N2O2), a new reagent for aromatization of Hantzsch 1,4-dihydropyridines. AB - A variety of Hantzsch 1,4-dihydropyridines were oxidized to their corresponding pyridines in high yields in the presence of Cu(C22H22N2O2) in refluxing acetic acid. PMID- 17851403 TI - Solventless lactam synthesis by intramolecular cyclizations of alpha-iminoester derivatives under microwave irradiation. AB - We have previously reported a new synthesis of amides from esters and amines under microwave irradiation, offering much higher yields than those achieved with conventional heating [1]. We have now extended these studies to the ring closure of neat iminoesters I2, I3 and I4-I6 to give five- and six-membered ring lactams L5, L6 and larger lactams L7-L9 (where I means imine and L means lactam), respectively, under both classical heating conditions and microwave irradiation. PMID- 17851404 TI - Occurrence, biological activities and synthesis of kaurane diterpenes and their glycosides. AB - This paper presents a review on kaurane diterpenes and their glycoside derivatives, covering aspects of their occurrence, biological activities and the synthesis of these natural products and their analogues. First, it shows and classifies diterpenes, in accordance with the already established structural criteria in the literature. Then, kaurane diterpenes are presented, focusing on their chemical structures, occurrence in the plant kingdom and their main, recently described, biological activities. Moreover, the most significant works, published between 1964 and November 2006, which describe the total synthesis or structural transformations of some kaurane diterpenes, including either semisynthetic and/or microbiological methodologies, are consisely reviewed. At this point, some general considerations on glycosides are introduced, and kaurane glycosides are presented and discussed on the basis of their toxic importance and occurrence in the plant kingdom, having focused on related aspects of their biological activities and the relationships between these activities and the structural factors of their molecules. Finally, the principal methods of glycosidation by enzymatic and chemical processes are both presented, and a few papers on the synthesis of kaurane glycosides are succinctly discussed. PMID- 17851405 TI - Effect of extraction conditions on measured total polyphenol contents and antioxidant and antibacterial activities of black tea. AB - Black tea was extracted for 2, 8 and 18 h with absolute acetone, N,N-dimethyl formamide (DMF), ethanol and methanol and their 50% aqueous solutions. The extracts were screened for total polyphenol contents, antioxidant and antibacterial activities. The polyphenol content of the extracts was found to be in the range of 0.44-114.01 mg gallic acid equivalents (GAE)/g dry weight tea, depending on the solvent used and the length of the extraction process. In general, aqueous acetone or DMF extracts displayed the highest polyphenol contents and antioxidant activity, while absolute acetone was the least efficient solvent. Antioxidant activities of tea extracts tested using the reducing power and 2,2-diphenyl-1-picryhydrazyl (DPPH) radical methods ranged from 0.09 to 1.18 and from 2.60 to 95.42 %, respectively, depending on the extraction conditions and the antioxidant activities correlated well with the polyphenol concentrations. Aqueous solvent black tea extracts also possessed antibacterial activity, depending on the solvent used and bacterial species tested. Staphylococcus aureus was found to be the most sensitive to all tea extracts, except for the methanol extract. Tea extracts were not effective against Y. enterocolitica, L. monocytogenes and E. coli O157:H7. PMID- 17851406 TI - Facile synthesis of some novel pyrido[3',2':4,5]thieno[2,3-b][1,4]thiazine-8 carboxylic acids. AB - Model tetrahydropyrido[3',2':4,5]thieno[2,3-b][1,4]thiazines 9a-c were synthesized via reductive lactamization, using sodium dithionite, of the respective 2-[(carboxyalkyl)thio]-3-nitro-4,7-dihydrothieno[2,3-b]pyridine-5 carboxylic acids 7a-c. The latter derivatives were made via interaction of 2 chloro-7-cyclopropyl-3-nitro-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylic acid (6) with each of alpha-mercaptoacetic, alpha-mercaptopropionic, and alpha mercaptosuccinic acids and triethylamine in aqueous acetone at room temperature. The structures of 7a-7c and 9a-9c are supported by microanalytical and spectral (IR, MS, NMR) data. Compounds 9a and 9c showed potent inhibitory activity against the IGROV1 (Ovarian Cancer) cell line. PMID- 17851407 TI - Isoselenocyanates: a powerful tool for the synthesis of selenium-containing heterocycles. AB - Selenium-containing heterocyclic compounds have been well recognized, not only because of their remarkable reactivities and chemical properties, but also because of their diverse pharmaceutical applications. In this context, isoselenocyanates have been emerged as a powerful tool for the synthesis of selenium-containing heterocycles, since they are easy to prepare and store and are safe to handle. In this review the recent advances in the development of synthesis methods for selenium-containing heterocycles from isoselenocyanates are presented and discussed. PMID- 17851408 TI - New cytotoxic steroid from Stachyurus imalaicus var. himalaicus. AB - A phytochemical study of the ethanolic extract of Stachyurus imalaicus var. himalaicus was undertaken and as a result a new polyoxygenated steroid, named stachsterol ((20S)-20, 25-dihydroxy-4-cholesten-3-one, 1) and three known ecdysteroids, 20-hydroxyecdysone (2), 20-hydroxyecdysone-20, 22-monoacetonide (3) and polypodine B-20,22-monoacetonide (4), were isolated. Their structures were elucidated by spectroscopic methods, including UV, NMR, MS and HR-MS. The purified product 1 was found to have in vitro cytotoxic activity against human Hela cell lines with an IC50 value of 2.5 microg/mL. This is the first time that phytoecdysteroids have been found in the genus Stachyurus. PMID- 17851409 TI - Microwave-promoted facile and efficient preparation of N-(alkoxycarbonylmethyl) nucleobases--building blocks for peptide nucleic acids. AB - A simple, rapid, and regioselective approach for the synthesis of N-(methoxy carbonylmethyl)- and N-(n-propoxycarbonylmethyl) nucleobases was developed. By using DMF as the solvent and in the presence of K2CO3 as the base, all the desired products were obtained in moderate yields within 8 min under microwave irradiation. PMID- 17851410 TI - Preparative separation and identification of the flavonoid phlorhizin from the crude extract of Lithocarpus polystachyus Rehd. AB - The flavonoid phlorhizin is abundant in the leaves of Sweet Tea (ST, Lithocarpus Polystachyus Rehd). Phlorhizin was preparatively separated and purified from a crude ST extract containing 40% total flavonoids by static adsorption and dynamic desorption on ADS-7 macroporous resin and neutral alumina column chromatography. Only water and ethanol were used as solvents and eluants throughout the whole separation and purification process. Using a phlorhizin standard as the reference compound, the target compound separated from the crude ST extracts was analyzed by thin layer chromatography (TLC), high performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (EIS-MS) and identified as 99.87% pure (by HPLC-UV) phlorhizin. The results showed that 10 g of the target compound could be obtained from 40 g of the crude extracts in a single operation, indicating a 40% recovery. Therefore, this represents an efficient and environmentally-friendly technology for separating and purifying phlorhizin from ST leaves. PMID- 17851411 TI - Symmetrically and unsymmetrically bridged methylenebis(allopurinols): synthesis of dimeric potential anti-gout drugs. AB - Liquid-liquid phase transfer alkylation of 4-methoxy-pyrazolo[3,4-d]-pyrimidine (1a) with a dichloromethane/dibromomethane mixture (3:1, v/v) gave the regioisomeric methylenebis(heterocycles) 3a-5a. These were converted by dilute aqueous sodium hydroxide containing dimethylsulfoxide (DMSO) at concentrations between 0 and 60 vol-% into the methylenebis(allopurinols) 3b-5b by nucleophilic SNAr reactions at C(4). The effect of DMSO on the reaction kinetics was investigated. PMID- 17851412 TI - Phenolic content and antioxidant properties of soybean (Glycine max (L.) Merr.) seeds. AB - The contents and antioxidant ability of various classes of phenolic compounds present in the seeds of twenty soybean hybrids were evaluated. Total phenolics, tannins and proanthocyanidins were determined spectrophotometrically, after extraction of seeds with 70% aqueous acetone. In addition, the flavonoid contents were determined. The antioxidant activity of aqueous acetone extracts was evaluated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity assay. The highest contents of total phenolics were found in Serbian cultivar 1511 and Chinese cultivar LN92-7369, which also displayed the highest total antioxidant activity. Conversely, genotypes poor in phenolics also showed low levels of DPPH-radical scavenging activity. The results suggested that besides protein and oil contents, the phenolic contents should be also considered as an important characteristic feature of soybean seeds, and as a potential selection criterion for antioxidant activity in soybean. PMID- 17851413 TI - Proteasome and NF-kappaB inhibiting phaeophytins from the green alga Cladophora fascicularis. AB - Chemical examination of the green alga Cladophora fascicularis resulted in the isolation and characterization of a new porphyrin derivative, porphyrinolactone (1), along with five known phaeophytins 2-6 and fourteen sterols and cycloartanes. The structure of 1 was determined on the basis of spectroscopic analyses and by comparison of its NMR data with those of known phaeophytins. Compounds 1-6 displayed moderate inhibition of tumor necrosis factor alpha (TNF alpha) induced nuclear factor-kappaB (NF-kappaB) activation, while 2 and 4 displayed potential inhibitory activity toward proteasome chymotripsin-like activation. The primary structure-activity relationship was also discussed. PMID- 17851414 TI - Characterization of flavonoid subgroups and hydroxy substitution by HPLC-MS/MS. AB - HPLC-DAD coupled with mass spectrometry in the positive ionization mode was applied to study the fragmentation of twelve selected flavonoids. Compounds belonging to all the major subgroups found in common plants, i.e. flavonols, flavones, dihydroflavonols, flavanones and flavanols were studied. Compound standards were injected into the spectrometer and produced characteristic mass spectra. The fragmentation of each compound was studied and it was shown that the dehydration and carbon monoxide losses from the [M+H]+ ion by the members of each subgroup produced specific fragments, thus allowing the characterization of the flavonoid subgroups. Moreover, fragments resulting from fission of the C-rings are specific of each subgroup and revealed the substitution pattern of A- and B rings. In order to verify the identifying efficiency of the positive ionization mode through these characteristic fragmentations, the unknown flavonoids of an Origanum vulgare diethyl ether extract were separated with the HPLC system and the major peaks were successfully identified with the mass spectrometer. PMID- 17851415 TI - Methyl jasmonate and salicylic acid induced oxidative stress and accumulation of phenolics in Panax ginseng bioreactor root suspension cultures. AB - To investigate the enzyme variations responsible for the synthesis of phenolics, 40 day-old adventitious roots of Panax ginseng were treated with 200 microM methyl jasmonate (MJ) or salicylic acid (SA) in a 5 L bioreactor suspension culture (working volume 4 L). Both treatments caused an increase in the carbonyl and hydrogen peroxide (H2O2) contents, although the levels were lower in SA treated roots. Total phenolic, flavonoid, ascorbic acid, non-protein thiol (NPSH) and cysteine contents and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical reducing activity were increased by MJ and SA. Fresh weight (FW) and dry weight (DW) decreased significantly after 9 days of exposure to SA and MJ. The highest total phenolics (62%), DPPH activity (40%), flavonoids (88%), ascorbic acid (55%), NPSH (33%), and cysteine (62%) contents compared to control were obtained after 9 days in SA treated roots. The activities of glucose 6-phosphate dehydrogenase, phenylalanine ammonia lyase, substrate specific peroxidases (caffeic acid peroxidase, quercetin peroxidase and ferulic acid peroxidase) were higher in MJ treated roots than the SA treated ones. Increased shikimate dehydrogenase, chlorogenic acid peroxidase and beta-glucosidase activities and proline content were observed in SA treated roots than in MJ ones. Cinnamyl alcohol dehydrogenase activity remained unaffected by both MJ and SA. These results strongly indicate that MJ and SA induce the accumulation of phenolic compounds in ginseng root by altering the phenolic synthesis enzymes. PMID- 17851416 TI - Synthesis and in vitro evaluation of new benzothiazole derivatives as schistosomicidal agents. AB - A series of benzothiazol-2-yl-dithiocarbamates 3a-d along with their copper complexes 4a-c were synthesized via the reaction of suitable alkyl, aralkyl or heteroaryl halides with the sodium salt of benzothiazol-2-yl-dithiocarbamic acid, followed by complexation with copper sulphate. N-(4-Acetyl-5-aryl-4,5-dihydro 1,3,4-thiadiazol-2-yl)-N-benzothiazol-2-yl-acetamides 7a-c were synthesized by cyclization of the appropriate thiosemicarbazones 6a-c in acetic anhydride. Selected compounds were screened for in vitro schistosomicidal activity against Schistosoma mansoni at three different dosage levels (10, 50 and 100 microg/mL). Three of these products, 4a-c, showed schistosomicidal activity similar to praziquantel, with 100% worm mortality at 10 microg/mL. These compounds would constitute a new class of potent schistosomicidal agents. PMID- 17851417 TI - Synthesis of 5-acetoxymethyl- and 5-hydroxymethyl-2-vinyl-furan. AB - 5-Acetoxymethyl- and 5-hydroxymethyl-2-vinylfuran were synthesized by two routes. The first route starts from 2-methylfuran and the second from furfuryl acetate. The latter route, involving successive Vilsmeier-Haack and Wittig reactions, is suitable for producing 5-acetoxymethyl-2-vinylfuran and 5-hydroxymethyl-2 vinylfuran in 68% and 60%yields, respectively. PMID- 17851418 TI - Novel aflatoxin derivatives and protein conjugates. AB - Aflatoxins, a group of structurally related mycotoxins, are well known for their toxic and carcinogenic effects in humans and animals. Aflatoxin derivatives and protein conjugates are needed for diverse analytical applications. This work describes a reliable and fast synthesis of novel aflatoxin derivatives, purification by preparative HPLC and characterisation by ESI-MS and one- and two dimensional NMR. Novel aflatoxin bovine serum albumin conjugates were prepared and characterised by UV absorption and MALDI-MS. These aflatoxin protein conjugates are potentially interesting as immunogens for the generation of aflatoxin selective antibodies with novel specificities. PMID- 17851419 TI - Identification of the products of oxidation of quercetin by air oxygen at ambient temperature. AB - Oxidation of quercetin by air oxygen takes place in water and aqueous ethanol solutions under mild conditions, namely in moderately-basic media (pH approximately 8-10) at ambient temperature and in the absence of any radical initiators, without enzymatic catalysis or irradiation of the reaction media by light. The principal reaction products are typical of other oxidative degradation processes of quercetin, namely 3,4-dihydroxy-benzoic (proto-catechuic) and 2,4,6 trihydroxybenzoic (phloroglucinic) acids, as well as the decarboxylation product of the latter--1,3,5-trihydroxybenzene (phloroglucinol). In accordance with the literature data, this process involves the cleavage of the gamma-pyrone fragment (ring C) of the quercetin molecule by oxygen, with primary formation of 4,6 dihydroxy-2-(3,4-dihydroxybenzoyloxy)benzoic acid (depside). However under such mild conditions the accepted mechanism of this reaction (oxidative decarbonylation with formation of carbon monoxide, CO) should be reconsidered as preferably an oxidative decarboxylation with formation of carbon dioxide, CO2. Direct head-space analysis of the gaseous components formed during quercetin oxidation in aqueous solution at ambient temperature indicates that the ratio of carbon dioxide/carbon monoxide in the gas phase after acidification of the reaction media is ca. 96:4%. Oxidation under these mild conditions is typical for other flavonols having OH groups at C3 (e.g., kaempferol), but it is completely suppressed if this hydroxyl group is substituted by a glycoside fragment (as in rutin), or a methyl substituent. An alternative oxidation mechanism involving the direct cleavage of the C2-C3 bond in the diketo-tautomer of quercetin is proposed. PMID- 17851420 TI - Synthesis of gefitinib from methyl 3-hydroxy-4-methoxy-benzoate. AB - This paper reports a novel synthesis of gefitinib starting from methyl 3-hydroxy 4-methoxybenzoate. The process starts with alkylation of the starting material, followed by nitration, reduction, cyclization, chlorination and two successive amination reactions. The intermediates and target molecule were characterized by 1H-NMR, 13C-NMR, MS and the purities of all these compounds were determined by HPLC. This novel synthetic route produced overall yields as high as 37.4%. PMID- 17851421 TI - Screening non-colored phenolics in red wines using liquid chromatography/ultraviolet and mass spectrometry/mass spectrometry libraries. AB - Liquid chromatography/ultraviolet (LC/UV) and mass spectrometry/mass spectrometry (MS/MS) libraries containing 39 phenolic compounds were established by coupling a LC and an ion trap MS with an electrospray ionization (ESI) source, operated in negative ion mode. As a result, the deprotonated [M-H]- molecule was observed for all the analyzed compounds. Using MS/MS hydroxybenzoic acid and hydroxycinnamic acids showed a loss of CO2 and production of a [M-H-44]- fragment and as expected, the UV spectra of these two compounds were affected by their chemical structures. For flavonol and flavonol glycosides, the spectra of their glycosides and aglycones produced deprotonated [M-H]- and [A-H]- species, respectively, and their UV spectra each presented two major absorption peaks. The UV spectra and MS/MS data of flavan-3-ols and stilbenes were also investigated. Using the optimized LC/MS/MS analytical conditions, the phenolic extracts from six representative wine samples were analyzed and 31 phenolic compounds were detected, 26 of which were identified by searching the LC/UV and MS/MS libraries. Finally, the presence of phenolic compounds was confirmed in different wine samples using the LC/UV and LC/MS/MS libraries. PMID- 17851422 TI - Fast and highly efficient solid state oxidation of thiols. AB - A fast and efficient solid state method for the chemoselective room temperature oxidative coupling of thiols to afford their corresponding disulfides using inexpensive and readily available moist sodium periodate as the reagent is described. The reaction was applicable to a variety of thiols giving high yields after short reaction times. Comparison of yield/time ratios of this method with some of those reported in the literature shows the superiority of this reagent over others under these conditions. PMID- 17851423 TI - Investigation on the binding of polycyclic aromatic hydrocarbons with soil organic matter: a theoretical approach. AB - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants of the terrestrial environment that have been designated as Environmental Protection Agency (EPA) Priority Pollutants. In this study, molecular modeling was used to examine the physical and chemical characteristics of soil organic matter (SOM), fulvic acid (FA) and humic acid (HA), as well as their binding interactions with PAHs. The molecular structures of 18 PAHs were built by using the SYBYL 7.0 program and then fully optimized by a semiempirical (AM1) method. A molecular docking program, AutoDock 3.05, was used to calculate the binding interactions between the PAHs, and three molecular structure models including FA (Buffle's model), HA (Stevenson's model) and SOM (Schulten and Schnitzer's model). The pi pi interactions and H-bonding interactions were found to play an important role in the intermolecular bonding of the SOM/PAHs complexes. In addition, significant correlations between two chemical properties, boiling point (bp) and octanol/water partition coefficient (Log K(ow)) and final docking energies were observed. The preliminary docking results provided knowledge of the important binding modes to FA, HA and SOM, and thereby to predict the sorption behavior of PAHs and other pollutants. PMID- 17851424 TI - Synthesis and X-ray structure of the inclusion complex of dodecamethylcucurbit[6]uril with 1,4-dihydroxybenzene. AB - The synthesis, and X-ray crystal structure of the inclusion host-guest complex of dodecamethylcucurbit[6]uril (DDMeQ[6]) with 1,4-dihydroxybenzene (DHOBEN) are reported. The complex crystallizes in the space group P21/c (No.14) with a =12.2847(4), b = 12.6895(4), c = 15.1310(4) A, alpha = 74.6960(10), beta = 71.4090(10), gamma = 86.5090(10) degrees and Z = 1. A novel approach to dodecamethylcucurbit[6]uril synthesis is also described. To separate dodecamethylcucurbit[6]uril, 1,4-dihydroxybenzene is used as a guest molecule for crystallization of the fully methyl-substituted cucurbituril. The driving force for the self-assembled inclusion host-guest complex can be attributed to not only the cavity interaction of dodecamethylcucurbit[6]uril (host), but also to the hydrogen bonding between the carbonyl oxygen at the portals of the host and the hydroxy groups of the guest. PMID- 17851425 TI - Multi-step redox systems with NIR-fluorescence based on 4H-imidazoles. AB - A new class of 4H-imidazoles was synthesized starting from fused-ring aromatic dinitriles. Strong bathochromic shifts of the longest wavelength absorptions were observed in the corresponding UV/vis spectra due to a conversion of the merocyanine chromophores into cyanines/(aza)oxonoles upon protonation/deprotonation of the 4H-imidazoles. Novel boratetraazapentalenes were synthesized via a cyclization reaction with boron trifluoride. These mesoionic species bearing a cyanine chromophore not only show NIR-fluorescence, they also participate as part of a quasi-reversible multi-step redox system. Large calculated semiquinone formation constants K(SEM) (3x10(10) to 5x10(11)) indicate a high thermodynamic stability of the corresponding radical anions (SEM). PMID- 17851426 TI - Synthesis of (R)-dihydropyridones as key intermediates for an efficient access to piperidine alkaloids. AB - The efficient transformation of D-glucal to (2R)-hydroxymethyldihydropyridinone 5 in seven steps and 35 % overall yield is reported. Dihydropyridone 5 constitutes a versatile chiral building block for the synthesis of various piperidine alkaloids. In this regard, 5 was converted to piperidinol 13 and piperidinone 15, that may be further elaborated for the syntheses of (+)-desoxoprosophylline (1) and deoxymannojirimycin (3) or D-mannolactam (4), respectively. PMID- 17851427 TI - Litchi flavonoids: isolation, identification and biological activity. AB - The current status of the isolation, identification, biological activity, utilization and development prospects of flavonoids found in litchi fruit pericarp (LFP) tissues is reviewed. LFP tissues account for approximately 15% by weight of the whole fresh fruit and are comprised of significant amount of flavonoids. The major flavonoids in ripe LFP include flavonols and anthocyanins. The major flavanols in the LFP are reported to be procyanidin B4, procyanidin B2 and epicatechin, while cyanindin-3-rutinside, cyanidin-3-glucoside, quercetin-3 rutinosde and quercetin-3-glucoside are identified as the important anthocyanins. Litchi flavanols and anthocyanins exhibit good potential antioxidant activity. The hydroxyl radical and superoxide anion scavenging activities of procyanidin B2 are greater than those of procyanidin B4 and epicatechin, while epicatechin has the highest alpha,alpha-diphenyl-beta-picrylhydrazyl radical (DPPH*) scavenging activity. In addition to the antioxidant activity, LFP extract displays a dose- and time-dependent inhibitory effect on human breast cancer, which could be attributed, in part, to its inhibition of proliferation and induction of apoptosis in cancer cells through upregulation and down-regulation of multiple genes. Furthermore, various anticancer activities are observed for epicatechin, procyanidin B2, procyanidin B4 and the ethyl acetate fraction of LFP tissue extracts. Procyanidin B4 and the ethyl acetate fraction show a stronger inhibitory effect on HELF than MCF-7 proliferation, while epicatechin and procyanidin B2 have lower cytotoxicities towards MCF-7 and HELF than paclitaxel. It is therefore suggested that flavonoids from LFP might be potentially useful components for functional foods and/or anti-breast cancer drugs. PMID- 17851428 TI - Evaluation of the antioxidant properties of litchi fruit phenolics in relation to pericarp browning prevention. AB - Phenolics were extracted from litchi fruit pericarp (LFP) tissues, purified and their antioxidant properties analyzed. LFP phenolics strongly inhibited linoleic acid oxidation and exhibited a dose-dependent free-radical scavenging activity against alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH*) and hydroxyl radicals and superoxide anions. The degradation of deoxyribose by hydroxyl radicals was inhibited by phenolics acting mainly as iron ion chelators, rather than by directly scavenging the radicals. Phenolics from litchi fruit pericarp were found to display similar reducing power activity as ascorbic acid. The effect of phenolic compound treatment on pericarp browning and electrolyte leakage of litchi fruit was also evaluated and it was observed that application of exogenous litchi phenolics to harvested litchi fruit significantly prevented pericarp browning and delayed increases in electrolyte leakage. These results suggest that litchi pericarp tissue phenolics could be beneficial in scavenging free radicals, maintaining membrane integrity and, thereby inhibiting pericarp browning of litchi fruit. PMID- 17851429 TI - Chemical composition and antimicrobial activity of the essential oil of Algerian Phlomis bovei De Noe subsp. bovei. AB - The chemical composition of essential oil obtained by steam distillation of dried aerial parts of Phlomis bovei De Noe subsp. bovei collected from Algeria, was analyzed by GC and GC/MS. Seventy five constituents (corresponding to 86.37% of the total weight) were identified. The main components were: germacrene D, beta caryophyllene, beta-bournonene, thymol and hexahydrofarnesyl acetone. Furthermore, the antimicrobial activity of the oil was evaluated against six gram (+/-) bacteria and three pathogenic fungi, using the agar dilution technique. It was found that the oil exhibited strong antimicrobial activity against most of the tested microorganisms. PMID- 17851430 TI - Complexes of 3d(n) metal ions with thiosemicarbazones: synthesis and antimicrobial activity. AB - The chelating behavior of the thiosemicarbazone derivatives of 2-hydroxy-8-R tricyclo[7.3.1.0.(2,7)]tridecane-13-one (where R = H, CH3, C6H5) towards Co(II), Ni(II) and Cu(II) has been investigated by elemental analysis, molar conductivity measurements, UV-VIS, IR, ESR spectroscopy and thermal studies. It was deduced from the experiments performed that the ligands coordinate to metal ions in different ways--neutral bidentate or mononegative bidentate--depending on the nature of R. Also, if metal acetates are used instead of metal chlorides, the ligands coordinate in a mononegative bidentate fashion, regardless of the nature of R or the thiosemicarbazone type ligand. The antimicrobial activity of the ligands and of the complexes towards samples of Acinetobacter boumanii, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa was determined. PMID- 17851431 TI - Synthesis of alpha,beta-unsaturated ketones as chalcone analogues via a S(RN)1 mechanism. AB - An electron-transfer chain reaction between 2-nitropropane anion and alpha bromoketones derived from nitrobenzene and nitrothiophene was demonstrated by mechanistic study and a specific convenient synthetic protocol. Thus, 2-bromo-1 (5-nitrothiophen-2-yl)ethanone or 2-bromo-1-(4-nitrophenyl)ethanone were reacted with several cyclic nitronate anions to form alpha,beta-unsaturated ketones via a S(RN)1 mechanism. This new method can be used to synthesize a wide variety of chalcone analogues. PMID- 17851432 TI - Molecularly imprinted polymers for 5-fluorouracil release in biological fluids. AB - The aim of this work was to investigate the possibility of employing Molecularly Imprinted Polymers (MIPs) as a controlled release device for 5-fluorouracil (5 FU) in biological fluids, especially gastrointestinal ones, compared to Non Imprinted Polymers (NIPs). MIPs were synthesized using methacrylic acid (MAA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent. The capacity of the polymer to recognize and to bind the template selectively in both organic and aqueous media was evaluated. An in vitro release study was performed both in gastrointestinal and in plasma simulating fluids. The imprinted polymers bound much more 5-Fu than the corresponding non-imprinted ones and showed a controlled/sustained drug release, with MIPs release rate being indeed much more sustained than that obtained from NIPs. These polymers represent a potential valid system for drug delivery and this study indicates that the selective binding characteristic of molecularly imprinted polymers is promising for the preparation of novel controlled release drug dosage form. PMID- 17851433 TI - Bis(4-hydroxybenzyl)sulfide: a sulfur compound inhibitor of histone deacetylase isolated from root extract of Pleuropterus ciliinervis. AB - A sulfur compound, bis(4-hydroxybenzyl)sulfide (1) was isolated from the root extract of Pleuropterus ciliinervis. Its structure was elucidated using NMR spectroscopic techniques and mass spectrometric analysis. Compound 1 showed potent inhibitory activity in a histone deacetylase (HDAC) enzyme assay. It also exhibited growth inhibitory activity on five human tumor cell lines and more sensitive inhibitory activity on the MDA-MB-231 breast tumor cell line. PMID- 17851434 TI - Different supramolecular coordination polymers of [N,N'-di(pyrazin-2-yl)-pyridine 2,6-diamine]Ni(II) with anions and solvent molecules as a result of hydrogen bonding. AB - Ni(II) complexes of N,N'-di(pyrazin-2-yl)pyridine-2,6-diamine (H2dpzpda) with different anions were synthesized and their structures were determined by X-ray diffraction. Hydrogen bonds between the amino groups and anions assembled the mononuclear molecules into different architectures. The perchlorate complex had a 1-D chain structure, whereas switching the anion from perchlorate to nitrate resulted in a corresponding change of the supramolecular structure from 1-D to 3 D. When the nitrate complex packed with the co-crystallized water, a double chain structure was formed through hydrogen bonding. The magnetic studies revealed values of g = 2.14 and D = 3.11 cm(-1) for [Ni(H2dpzpda)2](ClO4)2 (1) and g = 2.18 and D = 2.19 cm(-1) for [Ni(H2dpzpda)2](NO3)2 (2), respectively. PMID- 17851435 TI - Cytotoxic triterpenoid saponins from the roots of Platycodon grandiflorum. AB - Bioguided fractionation of the ethanol extracts obtained from Platycodon grandiflorum roots led to isolation of two new triterpenoid saponins, characterized as 3-O-beta-D-glucopyranosyl-2beta,12alpha,16alpha,23,24 pentahydroxyoleanane-28(13)-lactone (1) and 3-O-beta-D-glucopyranosyl-(1-->3) beta-D-glucopyranosyl-2beta,12alpha,16alpha,23alpha-tetrahydroxyoleanane-28(13) lactone (2) by 1D- and 2D-NMR and MS techniques, as well as chemical means. Both compounds showed cytotoxic activity against human ECA-109 cells. PMID- 17851436 TI - Identification of major phenolic compounds of Chinese water chestnut and their antioxidant activity. AB - Chinese water chestnut (CWC) is one of the most popular foods among Asian people due to its special taste and medical function. Experiments were conducted to test the antioxidant activity and then determine the major phenolic compound components present in CWC. CWC phenolic extract strongly inhibited linoleic acid oxidation and exhibited a dose-dependent free-radical scavenging activity against alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) radicals, superoxide anions and hydroxyl radicals, which was superior to ascorbic acid and butylated hydroxytoluene (BHT), two commercial used antioxidants. Furthermore, the CWC extract was found to have a relatively higher reducing power, compared with BHT. The major phenolic compounds present in CWC tissues were extracted, purified and identified by high-performance liquid chromatograph (HPLC) as (-)-gallocatechin gallate, (-)-epicatechin gallate and (+)-catechin gallate. This study suggests that CWC tissues exhibit great potential for antioxidant activity and may be useful for their nutritional and medicinal functions. PMID- 17851437 TI - Molecular complexes based on tetrathiafulvalene and dialkylviologens. AB - Three kinds of molecular complexes based on tetrathiafulvalene (TTF) and dialkylviologens were prepared and their crystal structures elucidated. While TTF dimethylviologen complex forms a mixed stack arrangement of donors and acceptors in its crystal structure, TTF donors aggregate with long alkyl groups by CH/pi and/or van der Waals interactions in a couple of TTF-heptylviologen complexes. PMID- 17851438 TI - C(aryl)-O bond formation from aryl methanesulfonates via consecutive deprotection and S(N)Ar reactions with aryl halides in an ionic liquid. AB - An efficient K3PO4-mediated synthesis of unsymmetrical diaryl ethers using the ionic liquid [Bmim]BF4 (1-butyl-3-methylimidazolium tetrafluoroborate) as solvent has been developed. The procedure involves consecutive deprotection of aryl methane-sulfonates and a nucleophilic aromatic substitution (S(N)Ar) with activated aryl halides. PMID- 17851439 TI - Microwave-assisted isolation of essential oil of Cinnamomum iners Reinw. ex Bl.: comparison with conventional hydrodistillation. AB - Microwave-assisted hydrodistillation was used to isolate an essential oil from the leaves of Cinnamomum iners Reinw. ex Bl., and the results compared with those obtained by conventional hydrodistillation. The composition of the oil from both methods was found to be similar, and (-)-linalool was found as the main component (30-50%). The antioxidant activity of the essential oil obtained by both methods was evaluated using DPPH, ABTS, FRAP and lipid peroxidation methods, all of which indicated the same but insignificant activity. PMID- 17851440 TI - How many drugs are catecholics. AB - By examination of the 8659 drugs recorded in the Comprehensive Medicinal Chemistry (CMC) database, 78 catecholics (including five pyrogallolics) were identified, of which 17 are currently prescribed by FDA. Through analyzing the substituent patterns, ClogPs and O-H bond dissociation enthalpies (BDEs) of the catecholic drugs, some molecular features that may benefit circumventing the toxicity of catecholics were revealed: i) strong electron-donating substituents are excluded; ii) ClogP 3; iii) an energy penalty exists for quinone formation. Besides, the present analyses also suggest that the clinical usage and dosage of currently prescribed catecholic drugs are of importance in designing or screening catecholic antioxidants. PMID- 17851441 TI - Synthesis and activity of a new series of (Z)-3-phenyl-2-benzoylpropenoic acid derivatives as aldose reductase inhibitors. AB - During the course of studies directed towards the discovery of novel aldose reductase inhibitors for the treatment of diabetic complications, we synthesized a series of new (Z)-3-phenyl-2-benzoylpropenoic acid derivatives and tested their in vitro inhibitory activities on rat lens aldose reductase. Of these compounds, (Z)-3-(3,4-dihydroxyphenyl)-2-(4-methylbenzoyl)propenoicacid (3k) was identified as the most potent inhibitor, with an IC50 of 0.49 microM. The theoretical binding mode of 3k was obtained by simulation of its docking into the active site of the human aldose reductase crystal structure. PMID- 17851442 TI - 4'-Acetamidochalcone derivatives as potential antinociceptive agents. AB - Nine acetamidochalcones were synthesized and evaluated as antinociceptive agents using the mice writhing test. Given intraperitoneally all the compounds were more effective than the two reference analgesic drugs (acetylsalicylic acid and acetaminophen) used for comparison. N-{4-[(2E)-3-(4-nitrophenyl)prop-2 enoyl]phenyl}acetamide (6) was the most effective compound and was therefore selected for more detailed studies. It caused dose-related inhibition in the writhing test, being about 32 to 34-fold more potent than the standard drugs. It was also effective in the second phase of the formalin test and the capsaicin test. These acetamidochalcones, especially compound 6, might be further used as models to obtain new and more potent analgesic drugs. PMID- 17851443 TI - Determination of the three-dimensional structure of Gynoside A in solution using NMR and molecular modeling. AB - The three-dimensional structure of Gynoside A, an ocotillone-type triterpenoid glycoside isolated from Gynostemma pentaphyllum, was determined in pyridine-d5 and DMSO-d6 solution through constrained molecular modeling using constraints derived from proton NMR spectra. The calculation yielded well-defined global minima. Except for some quantitative details the overall structure of Gynoside A in pyridine-d5 shared many common features with that in DMSO-d6. The structure in pyridine-d5 had lower energies than that in DMSO-d6 solution. PMID- 17851444 TI - Effects of different carriers on the production of isoflavone powder from soybean cake. AB - The objectives of this study were to use soybean cake as the raw material for the production of isoflavone powder and compare the effects of different carriers as well as drying methods on the powder quality. Results showed that with spray drying, a level of 40% maltodextrin as carrier produced the highest yield (mass) of isoflavone powder, followed by 10% gelatin and 1% sodium alginate. However, a reversed trend was observed for the isoflavone content. With 1% sodium alginate, freeze drying generated the greatest yield of isoflavone powder, followed by vacuum drying and spray drying. The isoflavone content also exhibited the same tendency. With poly-gamma-glutamic acid (gamma-PGA) as carrier, all six levels studied (0.57, 0.28, 0.14, 0.028, 0.014 and 0.003%) were capable of forming powder containing high amounts of total isoflavone, which was comparable to that using 1% sodium alginate by freeze drying. Both high- and low-molecular-weight gamma-PGA showed similar effects in terms of powder yield and isoflavone content. PMID- 17851445 TI - Ocular and respiratory illness associated with an indoor swimming pool--Nebraska, 2006. AB - On December 26, 2006, the Nebraska Department of Health and Human Services (NDHHS) received a report of a child hospitalized in an intensive care unit for severe chemical epiglottitis and laryngotracheobronchitis after swimming in an indoor motel swimming pool. The pool was inspected the same day and immediately closed by NDHHS because of multiple state health code violations. NDHHS initiated an outbreak investigation to identify additional cases and the cause of the illness. This report describes the results of that investigation, which indicated that 24 persons became ill, and the outbreak likely was the result of exposure to toxic levels of chloramines that had accumulated in the air in the enclosed space above the swimming pool. This outbreak highlights the potential health risks from chemical exposure at improperly maintained pools and the need for properly trained pool operators to maintain water quality. PMID- 17851446 TI - Colorectal cancer test use--Maryland, 2002-2006. AB - During 2000-2004, Maryland had the thirteenth highest mortality rate for colorectal cancer (CRC) among the 50 states and the District of Columbia. The American Cancer Society (ACS), the U.S. Preventive Services Task Force, and other organizations recommend that adults begin CRC screening at age 50 years if they are at average risk for CRC and before age 50 years if they are at increased risk. For those at average risk, ACS recommends screening with 1) a fecal occult blood test (FOBT) or fecal immunochemical test (FIT) every year, 2) flexible sigmoidoscopy every 5 years, 3) an annual FOBT or FIT combined with flexible sigmoidoscopy every 5 years, 4) double-contrast barium enema (DCBE) every 5 years, or 5) colonoscopy every 10 years. In 2002, the Maryland Department of Health and Mental Hygiene initiated the Maryland Cancer Survey (MCS) to assess testing prevalence and risk behaviors for seven types of cancer, including CRC. Reducing CRC mortality and disparities in CRC incidence and mortality are goals described in Maryland's Comprehensive Cancer Control Plan (MCCCP). As milestones toward these goals, Maryland set the following targets for 2008 for persons aged > or =50 years: 1) decrease the percentage of Maryland residents who have never been screened for CRC to < or =15% (from a 2002 baseline of 25.9%); 2) increase the percentage of residents who are up to date with CRC screening (per ACS guidelines) to > or =73% (from a 2002 baseline of 63.8%); and 3) increase the percentage of residents who have been screened with either colonoscopy in the past 10 years, or FOBT in the past year plus flexible sigmoidoscopy in the past 5 years, to > or =57% (from a baseline of 46.5% in 2002). This report describes trends in CRC test use based on results from MCS surveys completed in 2002, 2004, and 2006. The results indicated a significant decline (6.1 percentage points) in the percentage of Maryland residents aged > or =50 years who had never been tested for CRC, a 5.4 percentage-point increase in prevalence of up-to-date testing by any method, and a 13.9 percentage-point increase in prevalence of either colonoscopy in the past 10 years or FOBT in the past year plus flexible sigmoidoscopy in the past 5 years. However, Maryland residents who were neither white nor black (i.e., persons of other races) had a significantly lower prevalence of ever having a CRC test, as did persons without health insurance or those without a recent checkup. Although overall increases in CRC testing reflect substantial progress in Maryland, additional measures are needed to increase CRC testing among racial minority groups and the medically underserved. PMID- 17851447 TI - West Nile virus update--United States, January 1-September 11, 2007. AB - This report summarizes 2007 West Nile virus (WNV) surveillance data reported to CDC through ArboNET as of 3 a.m. Mountain Daylight Time, September 11, 2007. A total of 38 states have reported 1,395 cases of human WNV illness to CDC. A total of 770 (56%) cases for which such data were available occurred in males; median age of patients was 49 years (range: 15 months-96 years). Dates of illness onset ranged from January 8 to September 7; a total of 38 cases were fatal. PMID- 17851448 TI - Exposure scenarios for workers. AB - The new European chemicals legislation REACH (Registration, Evaluation, Authorisation and restriction of Chemicals) requires the development of Exposure Scenarios describing the conditions and risk management measures needed for the safe use of chemicals. Such Exposure Scenarios should integrate considerations of both human health and the environment. Specific aspects are relevant for worker exposure. Gathering information on the uses of the chemical is an important step in developing an Exposure Scenario. In-house information at manufacturers is an important source. Downstream users can contribute information through direct contact or through their associations. Relatively simple approaches (Tier 1 tools, such as the ECETOC Targeted Risk Assessment and the model EASE) can be used to develop broad Exposure Scenarios that cover many use situations. These approaches rely on the categorisation of just a few determinants, including only a small number of risk management measures. Such approaches have a limited discriminatory power and are rather conservative. When the hazard of the substance or the complexity of the exposure situation require a more in-depth approach, further development of the Exposure Scenarios with Tier 2 approaches is needed. Measured data sets of worker exposure are very valuable in a Tier 2 approach. Some downstream user associations have attempted to build Exposure Scenarios based on measured data sets. Generic Tier 2 tools for developing Exposure Scenarios do not exist yet. To enable efficient development of the worker exposure part of Exposure Scenarios a further development of Tier 1 and Tier 2 tools is needed. Special attention should be given to user friendliness and to the validity (boundaries) of the approaches. The development of standard worker exposure descriptions or full Exposure Scenarios by downstream user branches in cooperation with manufacturers and importers is recommended. PMID- 17851449 TI - Maternal amalgam dental fillings as the source of mercury exposure in developing fetus and newborn. AB - Dental amalgam is a mercury-based filling containing approximately 50% of metallic mercury (Hg(0)). Human placenta does not represent a real barrier to the transport of Hg(0); hence, fetal exposure occurs as a result of maternal exposure to Hg, with possible subsequent neurodevelopmental disabilities in infants. This study represents a substudy of the international NIH-funded project "Early Childhood Development and polychlorinated biphenyls Exposure in Slovakia". The main aim of this analysis was to assess the relationship between maternal dental amalgam fillings and exposure of the developing fetus to Hg. The study subjects were mother-child pairs (N=99). Questionnaires were administered after delivery, and chemical analyses of Hg were performed in the samples of maternal and cord blood using atomic absorption spectrometry with amalgamation technique. The median values of Hg concentrations were 0.63 microg/l (range 0.14-2.9 microg/l) and 0.80 microg/l (range 0.15-2.54 microg/l) for maternal and cord blood, respectively. None of the cord blood Hg concentrations reached the level considered to be hazardous for neurodevelopmental effects in children exposed to Hg in utero (EPA reference dose for Hg of 5.8 microg/l in cord blood). A strong positive correlation between maternal and cord blood Hg levels was found (rho=0.79; P<0.001). Levels of Hg in the cord blood were significantly associated with the number of maternal amalgam fillings (rho=0.46, P<0.001) and with the number of years since the last filling (rho=-0.37, P<0.001); these associations remained significant after adjustment for maternal age and education. Dental amalgam fillings in girls and women of reproductive age should be used with caution, to avoid increased prenatal Hg exposure. PMID- 17851450 TI - Multimedia measurements and activity patterns in an observational pilot study of nine young children. AB - A pilot observational exposure study was performed to evaluate methods for collecting multimedia measurements (air, dust, food, urine) and activity patterns to assess potential exposures of young children to pesticides in their homes. Nine children (mean age=5 years) and their caregivers participated in this study, performed in the Duval County, Florida, in collaboration with the Centers for Disease Control and Prevention and the Duval County Health Department. For all nine children, the total time reported for sleeping and napping ranged from 9.5 to 14 h per day, indoor quiet time from 0 to 5.5 h per day, indoor active time from 0.75 to 5.5 h per day, outdoor quiet time from 0 to 1.5 h per day, and outdoor active time from 0.5 to 6.5 h per day. Each home had one to three pesticide products present, with aerosols being most common. Pesticide inventories, however, were not useful for predicting pesticide levels in the home. Synthetic pyrethroids were the most frequently identified active ingredients in the products present in each home. Fifteen pesticide active ingredients were measured in the application area wipes (not detected (ND) to 580 ng/cm(2)), 13 in the play area wipes (ND-117 ng/cm(2)), and 14 in the indoor air samples (ND-378 ng/m(3)) and the socks (ND-1000 ng/cm(2)). Cis-permethrin, trans permethrin, and cypermethrin were measured in all nine homes. Chlorpyrifos was measured in all nine homes even though it was not reported used by the participants. All urine samples contained measurable concentrations of 3 phenoxybenzoic acid (3-PBA). The median 3-PBA urinary concentration for the nine children was 2.2 mug/l. A wide variety of pesticide active ingredients were measured in these nine homes at median concentrations that were often higher than reported previously in similar studies. These data highlight the need for additional observational studies in regions where pesticides are used in order to understand the factors that affect young children's exposures and the education/mitigation strategies that can be used to reduce children's exposures. PMID- 17851451 TI - Homozygous PMS2 germline mutations in two families with early-onset haematological malignancy, brain tumours, HNPCC-associated tumours, and signs of neurofibromatosis type 1. AB - Heterozygous germline mutations in mismatch repair (MMR) genes MLH1, PMS2, MSH2, and MSH6 cause Lynch syndrome. New studies have indicated that biallelic mutations lead to a distinctive syndrome, childhood cancer syndrome (CCS), with haematological malignancies and tumours of brain and bowel early in childhood, often associated with signs of neurofibromatosis type 1. We provide further evidence for CCS reporting on six children from two consanguineous families carrying homozygous PMS2 germline mutations. In family 1, all four children had the homozygous p.I590Xfs mutation. Two had a glioblastoma at the age of 6 years and one of them had three additional Lynch-syndrome associated tumours at 15. Another sibling suffered from a glioblastoma at age 9, and the fourth sibling had infantile myofibromatosis at 1. In family 2, two of four siblings were homozygous for the p.G271V mutation. One had two colorectal cancers diagnosed at ages 13 and 14, the other had a Non-Hodgkin's lymphoma and a colorectal cancer at ages 10 and 11, respectively. All children with malignancies had multiple cafe-au-lait spots. After reviewing published cases of biallelic MMR gene mutations, we provide a concise description of CCS, revealing similarities in age distribution with carriers of heterozygous MMR gene mutations. PMID- 17851452 TI - Unexpected genetic heterogeneity in a large consanguineous Brazilian pedigree presenting deafness. AB - Nonsyndromic autosomal recessive deafness accounts for 80% of hereditary deafness. To date, 52 loci responsible for autosomal recessive deafness have been mapped and 24 genes identified. Here, we report a large inbred Brazilian pedigree with 26 subjects affected by prelingual deafness. Given the extensive consanguinity found in this pedigree, the most probable pattern of inheritance is autosomal recessive. However, our linkage and mutational analysis revealed, instead of an expected homozygous mutation in a single gene, two different mutant alleles and a possible third undetected mutant allele in the MYO15A gene (DFNB3 locus), as well as evidence for other causes for deafness in the same pedigree. Among the 26 affected subjects, 15 were homozygous for the novel c.10573delA mutation in the MYO15A gene, 5 were compound heterozygous for the mutation c.10573delA and the novel deletion c.9957_9960delTGAC and one inherited only a single c.10573delA mutant allele, while the other one could not be identified. Given the extensive consanguinity of the pedigree, there might be at least one more deafness locus segregating to explain the condition in some of the subjects whose deafness is not clearly associated with MYO15A mutations, although overlooked environmental causes could not be ruled out. Our findings illustrate a high level of etiological heterogeneity for deafness in the family and highlight some of the pitfalls of genetic analysis of large genes in extended pedigrees, when homozygosity for a single mutant allele is expected. PMID- 17851453 TI - Apolipoprotein D is elevated in oligodendrocytes in the peri-infarct region after experimental stroke: influence of enriched environment. AB - Injury to the brain (e.g., stroke) results in a disruption of neuronal connectivity and loss of fundamental sensori-motor functions. The subsequent recovery of certain functions involves structural rearrangements in areas adjacent to the infarct. This remodeling of the injured brain requires trafficking of macromolecular components including cholesterol and phospholipids, a transport carried out by apolipoproteins including apolipoprotein D (apoD). We investigated the changes in the levels of apoD mRNA and protein, and its cellular localization during a recovery period up to 30 days after experimental stroke in the rat brain. In the core of the brain infarct, apoD immunoreactivity but not mRNA increased in dying pyramidal neurons, indicative of cellular redistribution of lipids. During 2 to 7 days of recovery after stroke, the apoD levels increased in the peri-infarct and white matter areas in cells identified as mature oligodendrocytes. The apoD expressing cells were conspicuously located along the rim of the infarct, suggesting a role for apoD in tissue repair. Furthermore, housing animals in an enriched environment improved sensori-motor function and increased the apoD levels. Our data strongly suggest that apoD is involved in regenerative processes and scar formation in the peri-infarct area presumably by enhancing lipid trafficking. PMID- 17851454 TI - Inducible nitric oxide synthase does not mediate brain damage after transient focal cerebral ischemia in mice. AB - Nitric oxide produced by the inducible nitric oxide synthase (iNOS) is believed to participate in the pathogenic events after cerebral ischemia. In this study, we examined the expression of iNOS in the brain after transient focal cerebral ischemia in mice. We detected differential expression of exons 2 and 3 of iNOS mRNA (16-fold upregulation at 24 to 72 h after middle cerebral artery occlusion, MCAO) compared with exons 6 to 8, 12 to 14, 21 to 22, and 26 to 27 (2- to 5-fold upregulation after 72 and 96 h), which would be compatible with alternative splicing. Expression levels of iNOS mRNA were too low for detection by the Northern blot analysis. Using specific antibodies, we did not detect any iNOS immunoreactivity in the mouse brain 1 to 5 days after MCAO, although we detected iNOS immunoreactivity in the lungs of mice with stroke-associated pneumonia, and in mouse and rat dura mater after lipopolysaccharide administration. In chimeric iNOS-deficient mice transplanted with wild-type bone marrow (BM) cells expressing the green fluorescent protein (GFP) or in wild-type mice transplanted with GFP(+) iNOS-deficient BM cells, no expression of iNOS was detected in GFP(+) leukocytes invading the ischemic brain or in resident brain cells. Moreover, both experimental groups did not show any differences in infarct size. Analysis of three different strains of iNOS-deficient mice and wild-type controls confirmed that infarct size was independent of iNOS deletion, but strongly confounded by the genetic background of mouse strains. In conclusion, our data suggest that iNOS is not a universal mediator of brain damage after cerebral ischemia. PMID- 17851455 TI - Acute astrocyte activation in brain detected by MRI: new insights into T(1) hypointensity. AB - Increases in the T(1) of brain tissue, which give rise to dark or hypointense areas on T(1)-weighted images using magnetic resonance imaging (MRI), are common to a number of neuropathologies including multiple sclerosis (MS) and ischaemia. However, the biologic significance of T(1) increases remains unclear. Using a multiparametric MRI approach and well-defined experimental models, we have experimentally induced increases in tissue T(1) to determine the underlying cellular basis of such changes. We have shown that a rapid acute increase in T(1) relaxation in the brain occurs in experimental models of both low-flow ischaemia induced by intrastriatal injection of endothelin-1 (ET-1), and excitotoxicity induced by intrastriatal injection of N-methyl-D-aspartate (NMDA). However, there appears to be no consistent correlation between increases in T(1) relaxation and changes in other MRI parameters (apparent diffusion coefficient, T(2) relaxation, or magnetisation transfer ratio of tissue water). Immunohistochemically, one common morphologic feature shared by the ET-1 and NMDA models is acute astrocyte activation, which was detectable within 2 h of intracerebral ET-1 injection. Pretreatment with an inhibitor of astrocyte activation, arundic acid, significantly reduced the spatial extent of the T(1) signal change induced by intrastriatal ET-1 injection. These findings suggest that an increase in T(1) relaxation may identify the acute development of reactive astrocytes within a central nervous system lesion. Early changes in T(1) may, therefore, provide insight into acute and reversible injury processes in neurologic patients, such as those observed before contrast enhancement in MS. PMID- 17851456 TI - Conflict of interests and consensus meetings. PMID- 17851457 TI - The new law: public law 109-462 for dietary supplements. PMID- 17851458 TI - Dietary patterns of urban adults in Benin: relationship with overall diet quality and socio-demographic characteristics. AB - OBJECTIVES: To identify dietary patterns of urban Beninese adults and explore their links with overall diet quality and socio-demographics. SUBJECTS AND METHODS: A sample of 200 men and women aged 25-60 years was randomly selected in 10 neighbourhoods. Food intake was assessed through three non-consecutive 24 h food recalls. Dietary patterns were examined using cluster analysis. Diet quality was assessed based on diversity, a micronutrient adequacy score (MAS) and a healthfulness score (HS). Socio-demographics were documented using a questionnaire. RESULTS: Two distinct dietary patterns emerged: a 'traditional' type (66% of the subjects) and a 'transitional' type (34%). Subjects with a 'transitional diet' were predominantly from the upper socioeconomic status or born in the city. Compared with the traditional type, the 'transitional diet' had a significantly higher percentage of energy from fat (17.6 vs 15.5%), saturated fat (5.9 vs 5.2%) and sugar (6.3 vs 5.0%). It was also significantly higher in cholesterol and lower in fibre. The 'transitional diet' was more diversified, but it also showed a lower HS than the 'traditional diet'. Mean intake of fruit was low in both clusters (<16 g day(-1)). A higher intake of vegetables was associated with both a higher MAS (P<0.001) and a higher HS (P<0.001). CONCLUSIONS: The dietary transition is evidenced in this study, although both dietary patterns were still low in fat and sugar. Programmes focusing on the prevention of diet-related chronic diseases in this population should encourage the maintenance of the healthful elements of the diets, while emphasizing consumption of fruits and vegetables. PMID- 17851459 TI - Effects of differences in postprandial glycaemia on cognitive functions in healthy middle-aged subjects. AB - OBJECTIVE: To find useful methods for the studies of cognitive function during a postprandial period, and to use these methods to evaluate function after test meals differing in post meal glycaemia. SUBJECTS/METHODS: Forty healthy volunteers aged 49-70 years were studied. A glucose solution (glucose 50 g) was provided through either a bolus or sipping regimen at breakfast to simulate a high-GI or a low-GI breakfast, respectively. Cognitive tests of working memory (WM) were performed at 35, 90, 120 and 150 min after commencing the breakfast, and a test of selective attention (SA) was performed at 170 min. RESULTS: Subjects with higher glucose tolerance performed better in the cognitive tests (P<0.05). After entering glucose tolerance as covariate, the subjects performed better in the working memory test at 90 min (P<0.034) and in the selective attention test at 170 min (P<0.017) after the simulated low-glycaemic index (GI) breakfast compared with the simulated high-GI breakfast. CONCLUSION: Possibly, the cognitive functions tested were enhanced by avoiding a sharp decline in blood glucose concentration and by maintaining a higher glycaemia in the late postprandial period, respectively. A low-GI diet is preferable in the prevention of the risk of cognitive decline as a result of less efficient glucose regulation. PMID- 17851460 TI - The effect of Lactobacillus helveticus fermented milk on sleep and health perception in elderly subjects. AB - OBJECTIVE: To study the effect of Lactobacillus helveticus fermented milk on sleep and health perception in elderly healthy subjects. SUBJECTS: The study included 29 healthy elderly subjects aged 60-81 years. METHODS: Prospective, randomized, double-blind and placebo-controlled, with a crossover design. The study included two intervention periods of 3 weeks each, separated by a 3-week washout period. Subjects took 100 g of fermented milk drink or a placebo drink (artificially acidified milk) daily in the first supplementary period and the other drink in the second supplementary period. For each period, we measured sleep quality by means of actigraphy and a sleep questionnaire, and assessed the quality of life (QOL) by SF-36 health survey. RESULTS: There was a significant improvement in sleep efficiency (P=0.03) and number of wakening episodes (P=0.007) in actigraph data after intake of fermented milk, whereas no significant changes were observed for the placebo. Fermented milk did not improve the SF-36 scores significantly from the baseline period. In the GH domain (general health perception) of the SF-36, however, there was marginal improvement as compared to the baseline period. Although the difference between fermented milk and placebo was not statistically significant for any of the sleep or QOL parameters, fermented milk produced slightly greater mean values for many parameters. CONCLUSION: This short-term (3-week) intervention study indicates that Lactobacillus helveticus fermented milk may have a more favorable effect on improving sleep in healthy elderly people as compared with placebo. PMID- 17851461 TI - Dietary intake and status of folate and vitamin B12 and their association with homocysteine and cardiovascular disease in European populations. AB - BACKGROUND/OBJECTIVES: Folate and vitamin B12 have been suggested to play a role in chronic diseases like cardiovascular diseases. The objectives are to give an overview of the actual intake and status of folate and vitamin B12 in general populations in Europe, and to evaluate these in view of the current vitamin recommendations and the homocysteine concentration. METHODS: Searches in Medline with 'folic acid', 'folate' and 'vitamin B12', 'B12' or 'cobalamin' as key words were combined with the names of the European countries. Populations between 18 and 65 years were included. RESULTS: Sixty-three articles reporting on studies from 15 European countries were selected. Low folate intakes were observed in Norway, Sweden, Denmark and the Netherlands. Low intakes of vitamin B12 were not common and only seen in one small Greek study. In the countries with a low intake of folate, the recommended levels were generally not achieved, which was also reflected in the folate status. Vitamin B12 intake was not strongly associated with the vitamin B12 status, which can explain why in the Netherlands and Germany the vitamin B12 status was inadequate, despite sufficient intake levels. In countries with a low folate intake in particular, the Hcy concentration was higher than ideal. CONCLUSIONS: Populations from the Nordic countries, the Netherlands, Germany and Greece may need to improve their intakes of folic acid, B12 or both to either meet the recommendations or to optimize their statuses. This could be achieved via a food-based approach, food fortification or supplements. PMID- 17851462 TI - The effect of different protein hydrolysate/carbohydrate mixtures on postprandial glucagon and insulin responses in healthy subjects. AB - OBJECTIVES: To study the effect of four protein hydrolysates from vegetable (pea, gluten, rice and soy) and two protein hydrolysates from animal origin (whey and egg) on glucagon and insulin responses. SUBJECTS/METHODS: Eight healthy normal weight male subjects participated in this study. The study employed a repeated measures design with Latin square randomization and single-blind trials. Protein hydrolysates used in this study (pea, rice, soy, gluten, whey and egg protein hydrolysate) consisted of 0.2 g hydrolysate per kg body weight (bw) and 0.2 g maltodextrin per kg bw and were compared to maltodextrin alone. Postprandial plasma glucose, glucagon, insulin and amino acids were determined over 2 h. RESULTS: All protein hydrolysates induced an enhanced insulin secretion compared to maltodextrin alone and a correspondingly low plasma glucose response. A significant difference was observed in area under the curve (AUC) for plasma glucagon between protein hydrolysates and the maltodextrin control drink (P<0.05). Gluten protein hydrolysate induced the lowest glucagon response. CONCLUSIONS: High amino-acid-induced glucagon response does not necessarily go together with low insulin response. Protein hydrolysate source affects AUC for glucagon more profoundly than for insulin, although the protein load used in this study seemed to be at lower level for significant physiological effects. PMID- 17851463 TI - Benzodiazepine use and mortality of incident dialysis patients in the United States. AB - Benzodiazepines and other omega-receptor agonists are frequently used for sleep and anxiety disorders. We studied the rates, correlates, and safety of individual benzodiazepines and zolpidem use from the records of 3690 patients in a national cohort of Dialysis Morbidity and Mortality Study Wave 2 data. We assessed drug utilization and an association between drug use and all-cause mortality. Overall, 14% of incident dialysis patients used a benzodiazepine or zolpidem. Women, Caucasians, current smokers, and patients with chronic obstructive pulmonary disease were more likely to use these drugs, whereas patients with cerebrovascular disease were less likely to use these drugs. In adjusted analyses, benzodiazepine or zolpidem use was associated with a 15% higher mortality rate. Chronic obstructive pulmonary disease significantly modified this association, suggesting that these patients were at higher risk. No association was found between benzodiazepine use and greater risk for hip fracture. We conclude that benzodiazepine or zolpidem use is common in incident dialysis patients and may be associated with greater mortality. Further studies are needed to elucidate the safety of these drugs in the dialysis population, which may lead to cautious and restrictive utilization of omega-receptor agonists in dialysis patients. PMID- 17851464 TI - Receptor-interacting protein 2 is a marker for resolution of peritoneal dialysis associated peritonitis. AB - There are no predictive factors for peritoneal dialysis-associated peritonitis; however, its resolution correlates with a cell-mediated Th1 immune response. We tested the hypothesis that induction of receptor-interacting protein 2 (RIP2), an assumed kinase linked with Th1 responses, is a useful marker in this clinical setting. Basal RIP2 expression was measured in human immune cells and during dialysis-associated peritonitis. RIP2 increased with bacterial toxin cell activation and the temporal profile for this differed depending on immune cell involvement in the innate or adaptive phases of the response. Importantly, RIP2 expression increased in peritoneal immune cells during dialysis-associated peritonitis and this upregulation correlated with clinical outcome. An early induction in peritoneal CD14(+) cells correlated with rapid resolution, whereas minimal induction correlated with protracted infection and with catheter loss in 36% of patients. These latter patients had higher levels of MCP-1 consistent with a delayed transition from innate to adaptive immunity. Our study shows that upregulation of RIP2 is a useful marker to monitor dialysis-associated peritonitis and in predicting the clinical outcome of these infections. PMID- 17851465 TI - Smad7 gene transfer inhibits peritoneal fibrosis. AB - Fibrosis mediated by transforming growth factor-beta (TGF-beta) is a common cause of peritoneal dialysis (PD) failure. In a model of peritoneal fibrosis, we tested the effect of Smad7, an inhibitor of TGF-beta signaling, using an ultrasound microbubble-mediated delivery system. Rats were given daily PD for 4 weeks and received Smad7 or control plasmid transfer. The ultrasound technique enhanced Smad7 expression in a dose-dependent manner in more than 80% of the peritoneal cells after 3 days. The expression decreased by 14 days, but this was corrected by a second gene transfer. The overexpression of Smad7 substantially inhibited Smad2/3 activation, TGF-beta, plasminogen activator inhibitor-1, extracellular matrix, and myofibroblast mRNA, and protein expression in the peritoneal cells. The decreased peritoneal injury included the rise of mass transfer of glucose, a reduction of the ultrafiltration rate, and fibrotic thickening. Our studies suggest that ultrasound-mediated Smad7 gene delivery may be useful in the prevention or treatment of dialysis-induced peritoneal fibrosis. PMID- 17851466 TI - Apoptosis in the kidneys of patients with type II diabetic nephropathy. AB - The occurrence and extent of apoptosis in the kidneys of patients with diabetic nephropathy is largely unknown. We evaluated apoptosis in renal biopsies obtained from patients with early or advanced type II diabetic nephropathy. Apoptosis was about 6- and 3-fold higher, respectively, in glomeruli and tubules in kidneys of patients with early nephropathy than in the normal kidney and this was not further increased in advanced diabetic nephropathy. Glomerular apoptosis was related directly to hemoglobin A1(c) and systolic blood pressure, whereas tubular cell apoptosis correlated to diabetes duration and low-density lipoprotein cholesterol. Fas, Fas ligand, and p38 mitogen-activated protein kinase expressions were enhanced in glomeruli and tubules; however, this did not correlate with apoptosis. In patients with proteinuria, apoptosis was associated with the subsequent loss of kidney function. When these parameters were subjected to multivariate analysis, only glomerular apoptosis retained a significant independent predictive value. Our findings suggest that apoptosis might be a clinically relevant mechanism of glomerular and tubular cell loss in proteinuric type II diabetic patients. PMID- 17851467 TI - Controversies in nephrology: response to 'renal albumin handling, facts, and artifacts'. AB - For 40 years indirect measurements of the glomerular sieving coefficient of albumin yielded very low values. The first direct measurement by 2-photon microscopy by Russo et al (Kidney Int (2007) 71, 504-513) gives values 50-times higher. This demonstrated that relatively large quantities of albumin are normally filtered based on size selectivity alone. Most of this albumin is retrieved and returned to the blood supply. These new discoveries represent a paradigm shift in our understanding of albumin processing by the kidney. They also serve to explain several anomalous aspects of previous studies on glomerular filtration and mechanism of albuminuria and support the fact that glomerular charge selectivity is not a major factor controlling glomerular permselectivity. PMID- 17851468 TI - Antiglomerular basement membrane disease with normal renal function. PMID- 17851469 TI - P-glycoprotein-deficient mice have proximal tubule dysfunction but are protected against ischemic renal injury. AB - The multidrug resistance gene 1 product, P-glycoprotein (P-gp), is expressed in several excretory organs, including the apical membrane of proximal tubules. After inducing acute renal failure, P-gp expression is upregulated and this might be a protective function by pumping out toxicants and harmful products of oxidative stress. We characterized renal function of P-gp knockout mice and studied its consequences in renal ischemic damage. Compared with wild-type mice, knockout mice have a lower glomerular filtration rate and renal plasma flow. An augmented urinary excretion of sodium, numerous amino acids, calcium, glucose, and low molecular weight proteins was observed along with an increased diuresis. A higher lithium plasma clearance in the knockout mice suggested proximal tubular dysfunction. Electron microscopy showed mitochondrial abnormalities in proximal tubular cells that could account for decreased adenosine triphosphate levels in the cortex. After inducing ischemia, wild-type mice showed a decrease in creatinine clearance and severe proximal tubular necrosis. In contrast, knockout mice had no signs of tubular damage. Our data indicate that P-gp knockout mice have impaired renal function but are protected against ischemic renal injury. PMID- 17851470 TI - Hypertension and albuminuria in chronic kidney disease mapped to a mouse chromosome 11 locus. AB - Chronic kidney disease (CKD) is a key cause of hypertension and a potent independent risk for cardiovascular disease. Epidemiological studies suggest a strong genetic component determining susceptibility for renal disease and, by inference, the associated cardiovascular risk. With a subtotal nephrectomy model of kidney disease, we found the 129S6 mouse strain to be very susceptible to the development of hypertension, albuminuria, and kidney injury, whereas the C57BL/6 strain is relatively resistant. Accordingly, we set out to map quantitative trait loci conferring susceptibility to hypertension and albuminuria using this model with F2 mice. We found significant linkage of the blood pressure trait to two loci. At D11Mit143, mice homozygous for the 129S6 allele had significantly higher systolic blood pressure than mice heterozygous or homozygous for the C57BL/6 allele. Similarly, at D1Mit308, there was an excellent correlation between genotype and the blood pressure phenotype. The effect of the chromosome 11 locus was verified with a separate cohort of F2 mice. For the albuminuria trait, a significant locus was found at D11Mit143, which overlaps the blood pressure trait locus. Our studies have identified a region spanning approximately 8 cM on mouse chromosome 11 that is associated with susceptibility to hypertension and albuminuria in CKD. PMID- 17851474 TI - Meeting obligations. Climate change should take ever-increasing priority in the Asia-Pacific region. PMID- 17851475 TI - Peer review reviewed. PMID- 17851476 TI - Turkey's transformation. PMID- 17851479 TI - Borysiewicz to head UK medical council. PMID- 17851480 TI - Russian scientists see red over clampdown. PMID- 17851481 TI - Long-held theory is in danger of losing its nerve. PMID- 17851482 TI - Mystery ox finds its identity. PMID- 17851484 TI - Interferon discovery and ferret flu. Jean Lindenmann interviewed by Alison Abbott. PMID- 17851487 TI - A commodity no more. PMID- 17851485 TI - Gorillas on the list. PMID- 17851488 TI - Accelerator physics: the plasma revolution. PMID- 17851489 TI - Fungal roles in soil ecology: underground networking. PMID- 17851491 TI - The Vietnam War added a motive to go on studying. PMID- 17851490 TI - Starstruck science should appreciate philosophy. PMID- 17851492 TI - Researchers' ethical duties are not to be outsourced. PMID- 17851493 TI - Cover story may obscure the plane truth. PMID- 17851494 TI - Cover: choosing the right gecko is a sticky business. PMID- 17851500 TI - Extrasolar planets: the one that got away. PMID- 17851495 TI - Universities and the money fix. PMID- 17851501 TI - Epigenetics: perceptive enzymes. PMID- 17851502 TI - Chemistry: molecular socks in a drawer. PMID- 17851503 TI - Ecology: scaling laws in the drier. PMID- 17851505 TI - Atomic physics: a whiff of antimatter soup. PMID- 17851506 TI - Evolutionary genetics: you are what you ate. PMID- 17851507 TI - Obituary: Ernst Otto Fischer (1918-2007). PMID- 17851509 TI - Lost in translation. PMID- 17851510 TI - A tough transition. PMID- 17851511 TI - The path to new medicines. PMID- 17851512 TI - Mission possible. PMID- 17851513 TI - A prescription for drug delivery. PMID- 17851514 TI - Patent sense. PMID- 17851515 TI - At what price? PMID- 17851516 TI - The road to recovery. PMID- 17851517 TI - A giant planet orbiting the 'extreme horizontal branch' star V 391 Pegasi. AB - After the initial discoveries fifteen years ago, over 200 extrasolar planets have now been detected. Most of them orbit main-sequence stars similar to our Sun, although a few planets orbiting red giant stars have been recently found. When the hydrogen in their cores runs out, main-sequence stars undergo an expansion into red-giant stars. This expansion can modify the orbits of planets and can easily reach and engulf the inner planets. The same will happen to the planets of our Solar System in about five billion years and the fate of the Earth is matter of debate. Here we report the discovery of a planetary-mass body (Msini = 3.2M(Jupiter)) orbiting the star V 391 Pegasi at a distance of about 1.7 astronomical units (au), with a period of 3.2 years. This star is on the extreme horizontal branch of the Hertzsprung-Russell diagram, burning helium in its core and pulsating. The maximum radius of the red-giant precursor of V 391 Pegasi may have reached 0.7 au, while the orbital distance of the planet during the stellar main-sequence phase is estimated to be about 1 au. This detection of a planet orbiting a post-red-giant star demonstrates that planets with orbital distances of less than 2 au can survive the red-giant expansion of their parent stars. PMID- 17851518 TI - Dynamics of ice ages on Mars. AB - Unlike Earth, where astronomical climate forcing is comparatively small, Mars experiences dramatic changes in incident sunlight that are capable of redistributing ice on a global scale. The geographic extent of the subsurface ice found poleward of approximately +/-60 degrees latitude on both hemispheres of Mars coincides with the areas where ice is stable. However, the tilt of Mars' rotation axis (obliquity) changed considerably in the past several million years. Earlier work has shown that regions of ice stability, which are defined by temperature and atmospheric humidity, differed in the recent past from today's, and subsurface ice is expected to retreat quickly when unstable. Here I explain how the subsurface ice sheets could have evolved to the state in which we see them today. Simulations of the retreat and growth of ground ice as a result of sublimation loss and recharge reveal forty major ice ages over the past five million years. Today, this gives rise to pore ice at mid-latitudes and a three layered depth distribution in the high latitudes of, from top to bottom, a dry layer, pore ice, and a massive ice sheet. Combined, these layers provide enough ice to be compatible with existing neutron and gamma-ray measurements. PMID- 17851519 TI - The production of molecular positronium. AB - It has been known for many years that an electron and its antiparticle, the positron, may together form a metastable hydrogen-like atom, known as positronium or Ps (ref. 1). In 1946, Wheeler speculated that two Ps atoms may combine to form the di-positronium molecule (Ps2), with a binding energy of 0.4 eV. More recently, this molecule has been studied theoretically; however, because Ps has a short lifetime and it is difficult to obtain low-energy positrons in large numbers, Ps2 has not previously been observed unambiguously. Here we show that when intense positron bursts are implanted into a thin film of porous silica, Ps2 is created on the internal pore surfaces. We found that molecule formation occurs much more efficiently than the competing process of spin exchange quenching, which appears to be suppressed in the confined pore geometry. This result experimentally confirms the existence of the Ps2 molecule and paves the way for further multi-positronium work. Using similar techniques, but with a more intense positron source, we expect to increase the Ps density to the point where many thousands of atoms interact and can undergo a phase transition to form a Bose Einstein condensate. As a purely leptonic, macroscopic quantum matter-antimatter system this would be of interest in its own right, but it would also represent a milestone on the path to produce an annihilation gamma-ray laser. PMID- 17851520 TI - Coupling of surface temperatures and atmospheric CO2 concentrations during the Palaeozoic era. AB - Atmospheric carbon dioxide concentrations seem to have been several times modern levels during much of the Palaeozoic era (543-248 million years ago), but decreased during the Carboniferous period to concentrations similar to that of today. Given that carbon dioxide is a greenhouse gas, it has been proposed that surface temperatures were significantly higher during the earlier portions of the Palaeozoic era. A reconstruction of tropical sea surface temperatures based on the delta18O of carbonate fossils indicates, however, that the magnitude of temperature variability throughout this period was small, suggesting that global climate may be independent of variations in atmospheric carbon dioxide concentration. Here we present estimates of sea surface temperatures that were obtained from fossil brachiopod and mollusc shells using the 'carbonate clumped isotope' method-an approach that, unlike the delta18O method, does not require independent estimates of the isotopic composition of the Palaeozoic ocean. Our results indicate that tropical sea surface temperatures were significantly higher than today during the Early Silurian period (443-423 Myr ago), when carbon dioxide concentrations are thought to have been relatively high, and were broadly similar to today during the Late Carboniferous period (314-300 Myr ago), when carbon dioxide concentrations are thought to have been similar to the present-day value. Our results are consistent with the proposal that increased atmospheric carbon dioxide concentrations drive or amplify increased global temperatures. PMID- 17851521 TI - A link between large mantle melting events and continent growth seen in osmium isotopes. AB - Although Earth's continental crust is thought to have been derived from the mantle, the timing and mode of crust formation have proven to be elusive issues. The area of preserved crust diminishes markedly with age, and this can be interpreted as being the result of either the progressive accumulation of new crust or the tectonic recycling of old crust. However, there is a disproportionate amount of crust of certain ages, with the main peaks being 1.2, 1.9, 2.7 and 3.3 billion years old; this has led to a third model in which the crust has grown through time in pulses, although peaks in continental crust ages could also record preferential preservation. The 187Re-187Os decay system is unique in its ability to track melt depletion events within the mantle and could therefore potentially link the crust and mantle differentiation records. Here we employ a laser ablation technique to analyse large numbers of osmium alloy grains to quantify the distribution of depletion ages in the Earth's upper mantle. Statistical analysis of these data, combined with other samples of the upper mantle, show that depletion ages are not evenly distributed but cluster in distinct periods, around 1.2, 1.9 and 2.7 billion years. These mantle depletion events coincide with peaks in the generation of continental crust and so provide evidence of coupled, global and pulsed mantle-crust differentiation, lending strong support to pulsed models of continental growth by means of large-scale mantle melting events. PMID- 17851522 TI - Placing late Neanderthals in a climatic context. AB - Attempts to place Palaeolithic finds within a precise climatic framework are complicated by both uncertainty over the radiocarbon calibration beyond about 21,500 14C years bp and the absence of a master calendar chronology for climate events from reference archives such as Greenland ice cores or speleothems. Here we present an alternative approach, in which 14C dates of interest are mapped directly onto the palaeoclimate record of the Cariaco Basin by means of its 14C series, circumventing calendar age model and correlation uncertainties, and placing dated events in the millennial-scale climate context of the last glacial period. This is applied to different sets of dates from levels with Mousterian artefacts, presumably produced by late Neanderthals, from Gorham's Cave in Gibraltar: first, generally accepted estimates of about 32,000 14C years bp for the uppermost Mousterian levels; second, a possible extended Middle Palaeolithic occupation until about 28,000 14C years bp; and third, more contentious evidence for persistence until about 24,000 14C years bp. This study shows that the three sets translate to different scenarios on the role of climate in Neanderthal extinction. The first two correspond to intervals of general climatic instability between stadials and interstadials that characterized most of the Middle Pleniglacial and are not coeval with Heinrich Events. In contrast, if accepted, the youngest date indicates that late Neanderthals may have persisted up to the onset of a major environmental shift, which included an expansion in global ice volume and an increased latitudinal temperature gradient. More generally, our radiocarbon climatostratigraphic approach can be applied to any 'snapshot' date from discontinuous records in a variety of deposits and can become a powerful tool in evaluating the climatic signature of critical intervals in Late Pleistocene human evolution. PMID- 17851523 TI - Positive feedbacks promote power-law clustering of Kalahari vegetation. AB - The concept of local-scale interactions driving large-scale pattern formation has been supported by numerical simulations, which have demonstrated that simple rules of interaction are capable of reproducing patterns observed in nature. These models of self-organization suggest that characteristic patterns should exist across a broad range of environmental conditions provided that local interactions do indeed dominate the development of community structure. Readily available observations that could be used to support these theoretical expectations, however, have lacked sufficient spatial extent or the necessary diversity of environmental conditions to confirm the model predictions. We use high-resolution satellite imagery to document the prevalence of self-organized vegetation patterns across a regional rainfall gradient in southern Africa, where percent tree cover ranges from 65% to 4%. Through the application of a cellular automata model, we find that the observed power-law distributions of tree canopy cluster sizes can arise from the interacting effects of global-scale resource constraints (that is, water availability) and local-scale facilitation. Positive local feedbacks result in power-law distributions without entailing threshold behaviour commonly associated with criticality. Our observations provide a framework for integrating a diverse suite of previous studies that have addressed either mean wet season rainfall or landscape-scale soil moisture variability as controls on the structural dynamics of arid and semi-arid ecosystems. PMID- 17851524 TI - Spatial vegetation patterns and imminent desertification in Mediterranean arid ecosystems. AB - Humans and climate affect ecosystems and their services, which may involve continuous and discontinuous transitions from one stable state to another. Discontinuous transitions are abrupt, irreversible and among the most catastrophic changes of ecosystems identified. For terrestrial ecosystems, it has been hypothesized that vegetation patchiness could be used as a signature of imminent transitions. Here, we analyse how vegetation patchiness changes in arid ecosystems with different grazing pressures, using both field data and a modelling approach. In the modelling approach, we extrapolated our analysis to even higher grazing pressures to investigate the vegetation patchiness when desertification is imminent. In three arid Mediterranean ecosystems in Spain, Greece and Morocco, we found that the patch-size distribution of the vegetation follows a power law. Using a stochastic cellular automaton model, we show that local positive interactions among plants can explain such power-law distributions. Furthermore, with increasing grazing pressure, the field data revealed consistent deviations from power laws. Increased grazing pressure leads to similar deviations in the model. When grazing was further increased in the model, we found that these deviations always and only occurred close to transition to desert, independent of the type of transition, and regardless of the vegetation cover. Therefore, we propose that patch-size distributions may be a warning signal for the onset of desertification. PMID- 17851525 TI - A general integrative model for scaling plant growth, carbon flux, and functional trait spectra. AB - Linking functional traits to plant growth is critical for scaling attributes of organisms to the dynamics of ecosystems and for understanding how selection shapes integrated botanical phenotypes. However, a general mechanistic theory showing how traits specifically influence carbon and biomass flux within and across plants is needed. Building on foundational work on relative growth rate, recent work on functional trait spectra, and metabolic scaling theory, here we derive a generalized trait-based model of plant growth. In agreement with a wide variety of empirical data, our model uniquely predicts how key functional traits interact to regulate variation in relative growth rate, the allometric growth normalizations for both angiosperms and gymnosperms, and the quantitative form of several functional trait spectra relationships. The model also provides a general quantitative framework to incorporate additional leaf-level trait scaling relationships and hence to unite functional trait spectra with theories of relative growth rate, and metabolic scaling. We apply the model to calculate carbon use efficiency. This often ignored trait, which may influence variation in relative growth rate, appears to vary directionally across geographic gradients. Together, our results show how both quantitative plant traits and the geometry of vascular transport networks can be merged into a common scaling theory. Our model provides a framework for predicting not only how traits covary within an integrated allometric phenotype but also how trait variation mechanistically influences plant growth and carbon flux within and across diverse ecosystems. PMID- 17851526 TI - Dscam diversity is essential for neuronal wiring and self-recognition. AB - Neurons are thought to use diverse families of cell-surface molecules for cell recognition during circuit assembly. In Drosophila, alternative splicing of the Down syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 closely related transmembrane proteins of the immunoglobulin superfamily, each comprising one of 19,008 alternative ectodomains linked to one of two alternative transmembrane segments. These ectodomains show isoform-specific homophilic binding, leading to speculation that Dscam proteins mediate cell recognition. Genetic studies have established that Dscam is required for neural circuit assembly, but the extent to which isoform diversity contributes to this process is not known. Here we provide conclusive evidence that Dscam diversity is essential for circuit assembly. Using homologous recombination, we reduced the entire repertoire of Dscam ectodomains to just a single isoform. Neural circuits in these mutants are severely disorganized. Furthermore, we show that it is crucial for neighbouring neurons to express distinct isoforms, but that the specific identity of the isoforms expressed in an individual neuron is unimportant. We conclude that Dscam diversity provides each neuron with a unique identity by which it can distinguish its own processes from those of other neurons, and that this self-recognition is essential for wiring the Drosophila brain. PMID- 17851529 TI - A histone H3 lysine 27 demethylase regulates animal posterior development. AB - The recent discovery of a large number of histone demethylases suggests a central role for these enzymes in regulating histone methylation dynamics. Histone H3K27 trimethylation (H3K27me3) has been linked to polycomb-group-protein-mediated suppression of Hox genes and animal body patterning, X-chromosome inactivation and possibly maintenance of embryonic stem cell (ESC) identity. An imbalance of H3K27 methylation owing to overexpression of the methylase EZH2 has been implicated in metastatic prostate and aggressive breast cancers. Here we show that the JmjC-domain-containing related proteins UTX and JMJD3 catalyse demethylation of H3K27me3/2. UTX is enriched around the transcription start sites of many HOX genes in primary human fibroblasts, in which HOX genes are differentially expressed, but is selectively excluded from the HOX loci in ESCs, in which HOX genes are largely silent. Consistently, RNA interference inhibition of UTX led to increased H3K27me3 levels at some HOX gene promoters. Importantly, morpholino oligonucleotide inhibition of a zebrafish UTX homologue resulted in mis-regulation of hox genes and a striking posterior developmental defect, which was partially rescued by wild-type, but not by catalytically inactive, human UTX. Taken together, these findings identify a small family of H3K27 demethylases with important, evolutionarily conserved roles in H3K27 methylation regulation and in animal anterior-posterior development. PMID- 17851530 TI - Snapshots of nuclear pore complexes in action captured by cryo-electron tomography. AB - Nuclear pore complexes reside in the nuclear envelope of eukaryotic cells and mediate the nucleocytoplasmic exchange of macromolecules. Traffic is regulated by mobile transport receptors that target their cargo to the central translocation channel, where phenylalanine-glycine-rich repeats serve as binding sites. The structural analysis of the nuclear pore is a formidable challenge given its size, its location in a membranous environment and its dynamic nature. Here we have used cryo-electron tomography to study the structure of nuclear pore complexes in their functional environment, that is, in intact nuclei of Dictyostelium discoideum. A new image-processing strategy compensating for deviations of the asymmetric units (protomers) from a perfect eight-fold symmetry enabled us to refine the structure and to identify new features. Furthermore, the superposition of a large number of tomograms taken in the presence of cargo, which was rendered visible by gold nanoparticles, has yielded a map outlining the trajectories of import cargo. Finally, we have performed single-molecule Monte Carlo simulations of nuclear import to interpret the experimentally observed cargo distribution in the light of existing models for nuclear import. PMID- 17851531 TI - Structural basis for AMP binding to mammalian AMP-activated protein kinase. AB - AMP-activated protein kinase (AMPK) regulates cellular metabolism in response to the availability of energy and is therefore a target for type II diabetes treatment. It senses changes in the ratio of AMP/ATP by binding both species in a competitive manner. Thus, increases in the concentration of AMP activate AMPK resulting in the phosphorylation and differential regulation of a series of downstream targets that control anabolic and catabolic pathways. We report here the crystal structure of the regulatory fragment of mammalian AMPK in complexes with AMP and ATP. The phosphate groups of AMP/ATP lie in a groove on the surface of the gamma domain, which is lined with basic residues, many of which are associated with disease-causing mutations. Structural and solution studies reveal that two sites on the gamma domain bind either AMP or Mg.ATP, whereas a third site contains a tightly bound AMP that does not exchange. Our binding studies indicate that under physiological conditions AMPK mainly exists in its inactive form in complex with Mg.ATP, which is much more abundant than AMP. Our modelling studies suggest how changes in the concentration of AMP ([AMP]) enhance AMPK activity levels. The structure also suggests a mechanism for propagating AMP/ATP signalling whereby a phosphorylated residue from the alpha and/or beta subunits binds to the gamma subunit in the presence of AMP but not when ATP is bound. PMID- 17851532 TI - Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors. AB - Lineage commitment and differentiation to a mature cell type are considered to be unidirectional and irreversible processes under physiological conditions. The commitment of haematopoietic progenitors to the B-cell lineage and their development to mature B lymphocytes critically depend on the transcription factor encoded by the paired box gene 5 (Pax5). Here we show that conditional Pax5 deletion in mice allowed mature B cells from peripheral lymphoid organs to dedifferentiate in vivo back to early uncommitted progenitors in the bone marrow, which rescued T lymphopoiesis in the thymus of T-cell-deficient mice. These B cell-derived T lymphocytes carried not only immunoglobulin heavy- and light-chain gene rearrangements but also participated as functional T cells in immune reactions. Mice lacking Pax5 in mature B cells also developed aggressive lymphomas, which were identified by their gene expression profile as progenitor cell tumours. Hence, the complete loss of Pax5 in late B cells could initiate lymphoma development and uncovered an extraordinary plasticity of mature peripheral B cells despite their advanced differentiation stage. PMID- 17851533 TI - Light adaptation in cone vision involves switching between receptor and post receptor sites. AB - We see over an enormous range of mean light levels, greater than the range of output signals retinal neurons can produce. Even highlights and shadows within a single visual scene can differ approximately 10,000-fold in intensity-exceeding the range of distinct neural signals by a factor of approximately 100. The effectiveness of daylight vision under these conditions relies on at least two retinal mechanisms that adjust sensitivity in the approximately 200 ms intervals between saccades. One mechanism is in the cone photoreceptors (receptor adaptation) and the other is at a previously unknown location within the retinal circuitry that benefits from convergence of signals from multiple cones (post receptor adaptation). Here we find that post-receptor adaptation occurs as signals are relayed from cone bipolar cells to ganglion cells. Furthermore, we find that the two adaptive mechanisms are essentially mutually exclusive: as light levels increase the main site of adaptation switches from the circuitry to the cones. These findings help explain how human cone vision encodes everyday scenes, and, more generally, how sensory systems handle the challenges posed by a diverse physical environment. PMID- 17851534 TI - Crystal structure of the heterotrimer core of Saccharomyces cerevisiae AMPK homologue SNF1. AB - AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis in mammals and is an attractive target for drug discovery against diabetes, obesity and other diseases. The AMPK homologue in Saccharomyces cerevisiae, known as SNF1, is essential for responses to glucose starvation as well as for other cellular processes, although SNF1 seems to be activated by a ligand other than AMP. Here we report the crystal structure at 2.6 A resolution of the heterotrimer core of SNF1. The ligand-binding site in the gamma-subunit (Snf4) has clear structural differences from that of the Schizosaccharomyces pombe enzyme, although our crystallographic data indicate that AMP can also bind to Snf4. The glycogen-binding domain in the beta-subunit (Sip2) interacts with Snf4 in the heterotrimer but should still be able to bind carbohydrates. Our structure is supported by a large body of biochemical and genetic data on this complex. Most significantly, the structure reveals that part of the regulatory sequence in the alpha-subunit (Snf1) is sequestered by Snf4, demonstrating a direct interaction between the alpha- and gamma-subunits and indicating that our structure may represent the heterotrimer core of SNF1 in its activated state. PMID- 17851535 TI - Acute physiological and behavioral effects of intranasal methamphetamine in humans. AB - Intranasal methamphetamine abuse has increased dramatically in the past decade, yet only one published study has investigated its acute effects under controlled laboratory conditions. Thus, the current study examined the effects of single dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Eleven nontreatment-seeking methamphetamine abusers (two females, nine males) completed this four-session, in-patient, within-participant, double-blind study. During each session, one of four intranasal methamphetamine doses (0, 12, 25, and 50 mg/70 kg) was administered and methamphetamine plasma concentrations, cardiovascular, subjective, and psychomotor/cognitive performance effects were assessed before drug administration and repeatedly thereafter. Following drug administration, methamphetamine plasma concentrations systematically increased for 4 h postdrug administration then declined. Methamphetamine dose dependently increased cardiovascular measures and 'positive' subjective effects, with peaks occurring approximately 5-15 min after drug administration, when plasma levels were still ascending. In addition, cognitive performance on less complicated tasks was improved by all active methamphetamine doses, whereas performance on more complicated tasks was improved only by the intermediate doses (12 and 25 mg). These results show that intranasal methamphetamine produced predictable effects on multiple behavioral and physiological measures before peak plasma levels were observed. Of interest is the dissociation between methamphetamine plasma concentrations with cardiovascular measures and positive subjective effects, which might have important implications for potential toxicity after repeated doses. PMID- 17851537 TI - Stress, depression, and neuroplasticity: a convergence of mechanisms. AB - Increasing evidence demonstrates that neuroplasticity, a fundamental mechanism of neuronal adaptation, is disrupted in mood disorders and in animal models of stress. Here we provide an overview of the evidence that chronic stress, which can precipitate or exacerbate depression, disrupts neuroplasticity, while antidepressant treatment produces opposing effects and can enhance neuroplasticity. We discuss neuroplasticity at different levels: structural plasticity (such as plastic changes in spine and dendrite morphology as well as adult neurogenesis), functional synaptic plasticity, and the molecular and cellular mechanisms accompanying such changes. Together, these studies elucidate mechanisms that may contribute to the pathophysiology of depression. Greater appreciation of the convergence of mechanisms between stress, depression, and neuroplasticity is likely to lead to the identification of novel targets for more efficacious treatments. PMID- 17851538 TI - Anxiety as a developmental disorder. AB - There is increasing recognition that many psychiatric disorders including anxiety disorders are neurodevelopmental in their origins. Here, we review and integrate data from human studies and from animal models that point to a critical period during which neural circuits that mediate anxiety develop. We then postulate that this highly plastic critical period is a time of heightened responsiveness that is particularly susceptible to adverse events. We discuss these concepts in the context the current heightened interest in gene by environment interactions in psychiatric illness emphasizing the importance of the temporal relationship between gene action and environmental milieu. PMID- 17851536 TI - Persistent alterations in mesolimbic gene expression with abstinence from cocaine self-administration. AB - Cocaine-responsive gene expression changes have been described after either no drug abstinence or short periods of abstinence. Little data exist on the persistence of these changes after long-term abstinence. Previously, we reported that after discrete-trial cocaine self-administration and 10 days of forced abstinence, incubation of cocaine reinforcement was observable by a progressive ratio schedule. The present study used rat discrete-trial cocaine self administration and long-term forced abstinence to examine extinction responding, mRNA abundance of known cocaine-responsive genes, and chromatin remodeling. At 30 and 100 days of abstinence, extinction responding increased compared to 3-day abstinent rats. Decreases in both medial prefrontal cortex (mPFC) and nucleus accumbens c-fos, Nr4a1, Arc, and EGR1 mRNA were observed, and in most cases persisted, for 100 days of abstinence. The signaling peptides CART and neuropeptide Y (NPY) transiently increased in the mPFC, but returned to baseline levels following 10 days of abstinence. To investigate a potential regulatory mechanism for these persistent mRNA changes, levels of histone H3 acetylation at promoters for genes with altered mRNA expression were examined. In the mPFC, histone H3 acetylation decreased after 1 and 10 days of abstinence at the promoter for EGR1. H3 acetylation increased for NPY after 1 day of abstinence and returned to control levels by 10 days of abstinence. Behaviorally, these results demonstrate incubation after discrete-trial cocaine self-administration and prolonged forced abstinence. This incubation is accompanied by changes in gene expression that persist long after cessation of drug administration and may be regulated by chromatin remodeling. PMID- 17851539 TI - Alcohol relapse induced by discrete cues activates components of AP-1 transcription factor and ERK pathway in the rat basolateral and central amygdala. AB - Alcohol-related cues may induce relapse to heavy alcohol drinking and promote molecular adaptations in discrete brain regions. An exact nature of these molecular alterations is still unknown. In the present study, rats trained to self-administer ethanol were tested for cue-induced reinstatement of ethanol seeking after 30 days of abstinence. Next, a detailed immunocytochemical analysis of c-Fos activation was performed within seven nuclei of the amygdala. In the second experiment, c-Fos activation after reinstatement of ethanol seeking induced by discrete cues was compared with the activation pattern of its putative partner (c-Jun) and regulators (extracellular signal-regulated kinases and c-Jun N-terminal kinases). Reexposure to ethanol-associated context cues (an extinction session) potentiated c-Fos expression within the basolateral and central amygdala. Repeated presentation of ethanol-associated discrete cues in an extinction/reinstatement session led to even stronger c-Fos activation in the latter nuclei. In the second experiment, reexposure to the ethanol-associated context and discrete cues activated both c-Jun and extracellular signal-regulated kinases (ERK1/2) in the basolateral amygdala. Our observations suggest that the basolateral and central amygdala may be specifically involved in alcohol-seeking behavior induced by discrete cues. PMID- 17851540 TI - AMPA receptor potentiation can prevent ethanol-induced intoxication. AB - We present a substantial series of behavioral and imaging experiments, which demonstrate, for the first time, that increasing AMPA receptor-mediated neurotransmission via administration of potent and selective biarylsulfonamide AMPA potentiators LY404187 and LY451395 reverses the central effects of an acutely intoxicating dose of ethanol in the rat. Using pharmacological magnetic resonance imaging (phMRI), we observed that LY404187 attenuated ethanol-induced reductions in blood oxygenation level dependent (BOLD) in the anesthetized rat brain. A similar attenuation was apparent when measuring local cerebral glucose utilization (LCGU) via C14-2-deoxyglucose autoradiography in freely moving conscious rats. Both LY404187 and LY451395 significantly and dose-dependently reversed ethanol-induced deficits in both motor coordination and disruptions in an operant task where animals were trained to press a lever for food reward. Both prophylactic and acute intervention treatment with LY404187 reversed ethanol induced deficits in motor coordination. Given that LY451395 and related AMPA receptor potentiators/ampakines are tolerated in both healthy volunteers and elderly patients, these data suggest that such compounds may form a potential management strategy for acute alcohol intoxication. PMID- 17851541 TI - High-frequency afferent stimulation induces long-term potentiation of field potentials in the ventral tegmental area. AB - Excitatory synapses on dopamine neurons in the VTA can undergo both long-term potentiation and depression. Additionally, drug-induced plasticity has been found at VTA synapses, and is proposed to play a role in reward-related learning and addiction by modifying dopamine cell firing. LTP at these synapses is difficult to generate experimentally in that it requires an undisturbed intracellular milieu and is often small in magnitude. Here, we demonstrate the induction of LTP as a property of evoked field potentials within the VTA. Excitatory field potentials were recorded extracellularly from VTA neurons in acute horizontal midbrain slices. Using extracellular and intracellular recording techniques, we found that evoked field potentials originate within the VTA itself and are largely composed of AMPA receptor-mediated EPSPs and action potentials triggered by activation of glutamatergic synapses on both dopamine and GABA neurons. High frequency afferent stimulation (HFS) induced LTP of the field potential. The induction of this LTP was blocked by application of the NMDAR antagonist, d-APV, prior to HFS. As reported previously, glutamatergic synapses on GABA neurons did not express LTP while those on dopamine neurons did. We conclude that the potentiation of glutamatergic synapses on dopamine neurons is a major contributor to NMDA receptor-dependent LTP of the field potential. Field potential recordings may provide a convenient approach to explore the basic electrophysiological properties of VTA neurons and the development of addiction-related processes in this brain region. PMID- 17851542 TI - Brain neuroplasticity in healthy, hyperactive and psychotic children: insights from neuroimaging. AB - Noninvasive brain imaging permits longitudinal studies of anatomic brain development in healthy and psychiatrically ill children. The time course for gray matter maturation varies by region and parallels earlier histological studies, indicating dynamic patterns of overproduction and regression. Developmental trajectories vary in relation to gender, intelligence, and overall functioning. Twin studies show high heritability for brain volumes, which varies with region and with age. Diagnostically specific, illness-related changes as well as outcome associated plastic response are observed as illustrated for two pediatric populations, childhood-onset schizophrenia and attention-deficit/hyperactivity disorder, conditions which may be, in part, disorders of brain plasticity. PMID- 17851543 TI - Emerging roles of proteases in tumour suppression. AB - Proteases have long been associated with cancer progression because of their ability to degrade extracellular matrices, which facilitates invasion and metastasis. However, recent studies have shown that these enzymes target a diversity of substrates and favour all steps of tumour evolution. Unexpectedly, the post-trial studies have also revealed proteases with tumour-suppressive effects. These effects are associated with more than 30 different enzymes that belong to three distinct protease classes. What are the clinical implications of these findings? PMID- 17851544 TI - Molecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis. AB - Human breast cancers are heterogeneous, both in their pathology and in their molecular profiles. This suggests the hypothesis that breast cancers can initiate in different cell types, either breast epithelial stem cells or their progeny (transit amplifying cells or committed differentiated cells). In this respect, breast cancer could be viewed as being similar to haematological malignancies for which an analogous model has been proposed. Drawing such parallels might help to unravel the molecular nature of the initiating events in breast cancer and might have substantial clinical implications. PMID- 17851545 TI - The correct application of Mage's Johnson SB procedure for fitting exposure data. PMID- 17851546 TI - Application of a disease-regulated promoter is a safer mode of local IL-4 gene therapy for arthritis. AB - The application of disease-regulated promoters in local gene therapy for rheumatoid arthritis potentiates the development of a sophisticated treatment that relies on a restricted and fine-tuned supply of biologicals. Although several studies have investigated regulated promoters for achieving effective transgene expression during arthritis, none have explored their potential for minimizing deleterious effects arising from constitutive overexpression of transgenes under naive conditions. Using naive and collagen-induced arthritic mice, we examined the applicability of a hybrid interleukin-1 enhancer/interleukin-6 proximal promoter for achieving efficacious murine interleukin-4 gene therapy under arthritic conditions, while minimizing interleukin-4-induced inflammation under naive conditions. We found strong upregulation of transgene expression in virally transduced knee joints under arthritic conditions compared to levels in naive animals. Besides its responsiveness, the promoter strength proved sufficient for generating therapeutically efficacious levels interleukin-4, as demonstrated by the successful protection against cartilage erosion in collagen-induced arthritis. Most importantly, promoter-mediated restriction of the potent chemotactic interleukin-4 in naive animals strongly reduced the amounts of inflammatory cell influx. This study suggests the suitability of the interleukin-1 enhancer/interleukin-6 proximal promoter for the development of a local gene therapy strategy for rheumatoid arthritis that requires fine-tuned and restricted expression of transgenes with a pleiotrophic nature. PMID- 17851547 TI - Cell-specific and efficient expression in mouse and human B cells by a novel hybrid immunoglobulin promoter in a lentiviral vector. AB - The expression of genes specifically in B cells is of great interest in both experimental immunology as well as in future clinical gene therapy. We have constructed a novel enhanced B cell-specific promoter (Igk-E) consisting of an immunoglobulin kappa (Igk) minimal promoter combined with an intronic enhancer sequence and a 3' enhancer sequence from Ig genes. The Igk-E promoter was cloned into a lentiviral vector and used to control expression of enhanced green fluorescent protein (eGFP). Transduction of murine B-cell lymphoma cell lines and activated primary splenic B cells, with IgK-E-eGFP lentivirus, resulted in expression of eGFP, as analysed by flow cytometry, whereas expression in non-B cells was absent. The specificity of the promoter was further examined by transducing Lin(-) bone marrow with Igk-E-eGFP lentivirus and reconstituting lethally irradiated mice. After 16 weeks flow cytometry of lymphoid tissues revealed eGFP expression by CD19+ cells, but not by CD3+, CD11b+, CD11c+ or Gr-1+ cells. CD19+ cells were comprised of both marginal zone B cells and recirculating follicular B cells. Activated human peripheral mononuclear cells were also transduced with Igk-E-eGFP lentivirus under conditions of selective B-cell activation. The Igk-E promoter was able to drive expression of eGFP only in CD19+ cells, while eGFP was expressed by both spleen focus-forming virus and cytomegalovirus constitutive promoters in CD19+ and CD3+ lymphocytes. These data demonstrate that in these conditions the Igk-E promoter is cell specific and controls efficient expression of a reporter protein in mouse and human B cells in the context of a lentiviral vector. PMID- 17851548 TI - Myocarditis following adeno-associated viral gene expression of human soluble TNF receptor (TNFRII-Fc) in baboon hearts. AB - Sequestration of tumor necrosis factor-alpha (TNFalpha) by TNF-receptor immunoglobulin G (IgG)-Fc fusion proteins can limit heart failure progression in rodent models. In this study we directly injected an adeno-associated viruses (AAV)-2 construct encoding a human TNF receptor II IgG-Fc fusion protein (AAV TNFRII-Fc) into healthy baboon hearts and assessed virally encoded gene expression and clinical response. Adult baboons received direct cardiac injections of AAV-TNFRII-Fc ( approximately 5 x 10(12) viral/genomes/baboon) or an equivalent dose of AAV-2 empty capsids, and were analyzed after 5 or 12 weeks. Viral genomes were restricted to the myocardium, and routine analyses (blood cell counts, clinical chemistries) remained unremarkable. Echocardiograms were unchanged but electrocardiograms revealed marked ST- and T-wave changes consistent with myocarditis only in baboons receiving AAV-TNFRII-Fc. TNFRII serum levels peaked at approximately 3 times the baseline levels at 1-2 weeks postinjection and subsequently declined to baseline levels. TNFRII-Fc protein and transcripts were detected in the heart at harvest. After AAV injection, anti-AAV 2 antibody levels increased in all baboons, while anti-TNFRII-Fc could not be detected. Baboons that received AAV-TNFRII-Fc developed myocardial infiltrates including CD8+ cells. Thus, a cellular immune response to cardiac delivery of AAV encoding foreign proteins may be an important consideration for AAV-based cardiac gene therapy. PMID- 17851549 TI - Analysis of the exon 12 and 14 mutations of the JAK2 gene in Philadelphia chromosome-positive leukemia. PMID- 17851550 TI - Validation of NG2 antigen in identifying BP-ALL patients with MLL rearrangements using qualitative and quantitative flow cytometry: a prospective study. PMID- 17851552 TI - A new case with rare e6a2 BCR-ABL fusion transcript developing two new resistance mutations during imatinib mesylate, which were replaced by T315I after subsequent dasatinib treatment. PMID- 17851551 TI - MLL-AF9 and FLT3 cooperation in acute myelogenous leukemia: development of a model for rapid therapeutic assessment. AB - Human leukemias harboring chromosomal translocations involving the mixed lineage leukemia (MLL, HRX, ALL-1) gene possess high-level expression, and frequent activating mutations of the receptor tyrosine kinase FLT3. We used a murine bone marrow transplant model to assess cooperation between MLL translocation and FLT3 activation. We demonstrate that MLL-AF9 expression induces acute myelogenous leukemia (AML) in approximately 70 days, whereas the combination of MLL-AF9 and FLT3-ITD does so in less than 30 days. Secondary transplantation of splenic cells from diseased mice established that leukemia stem cells are present at a very high frequency of approximately 1:100 in both diseases. Importantly, prospectively isolated granulocyte macrophage progenitors (GMPs) coinfected with MLL-AF9 and FLT3-ITD give rise to a similar AML, with shorter latency than from GMP transduced with MLL-AF9 alone. Cooperation between MLL-AF9 and FLT3-ITD was further verified by real-time assessment of leukemogenesis using noninvasive bioluminescence imaging. We used this model to demonstrate that MLL-AF9/FLT3-ITD induced leukemias are sensitive to FLT3 inhibition in a 2-3 week in vivo assay. These data show that activated FLT3 cooperates with MLL-AF9 to accelerate onset of an AML from whole bone marrow as well as a committed hematopoietic progenitor, and provide a new genetically defined model system that should prove useful for rapid assessment of potential therapeutics in vivo. PMID- 17851553 TI - A novel nude mice model of human extranodal nasal type NK/T-cell lymphoma. AB - A novel nude mice model of human extranodal nasal type NK/T-cell lymphoma was established by subcutaneously implanting the sample taken from the patient with secondary extranodal nasal type NK/T-cell lymphoma of the stomach into the right axillary region of a BALB/c (nu/nu) nude mouse. This model had been successfully transplanted in vivo for thirty-two generations with a stable growth cycle. The survival rates of both resuscitation and transplantation were 100%. Histologically, the tumor cells were medium to large size and arranged in sheets, with a little mesenchyma, and disseminated almost in all passages of the lymphoma bearing nude mice. Immunologically, the tumor cells were positive for CD56, cytoplasmic CD3, granzyme B or TIA-1 and LMP1, sometimes for CD8 but negative for surface CD3, CD7, CD20 and CD1a. EBER1/2 was found. No T-cell receptor gamma gene rearrangement was detected in the transplanted tumors. Furthermore, both human sequencing-tagged sites SY14 and Y chromosome were detected by PCR or fluorescent in situ hybridization, respectively, in the transplanted tumor. The transplanted tumor in this novel nude mice model maintained the essential features of human extranodal nasal type NK/T-cell lymphoma, and it would be an ideal tool in vivo for further research of the tumor. PMID- 17851554 TI - Comparison of nilotinib and imatinib inhibition of FMS receptor signaling, macrophage production and osteoclastogenesis. PMID- 17851555 TI - Pulmonary arterial hypertension in primary myelofibrosis is common and associated with an altered angiogenic status. PMID- 17851556 TI - Recurrent in-frame insertion in C/EBPalpha TAD2 region is a polymorphism without prognostic value in AML. PMID- 17851557 TI - Non-specific amplification of patient-specific Ig/TCR gene rearrangements depends on the time point during therapy: implications for minimal residual disease monitoring. PMID- 17851559 TI - High incidence of acute promyelocytic leukemia in children in northwest Italy, 1980-2003: a report from the Childhood Cancer Registry of Piedmont. PMID- 17851558 TI - FLT3 regulates beta-catenin tyrosine phosphorylation, nuclear localization, and transcriptional activity in acute myeloid leukemia cells. AB - Deregulated accumulation of nuclear beta-catenin enhances transcription of beta catenin target genes and promotes malignant transformation. Recently, acute myeloid leukemia (AML) cells with activating mutations of FMS-like tyrosine kinase-3 (FLT3) were reported to display elevated beta-catenin-dependent nuclear signaling. Tyrosine phosphorylation of beta-catenin has been shown to promote its nuclear localization. Here, we examined the causal relationship between FLT3 activity and beta-catenin nuclear localization. Compared to cells with wild-type FLT3 (FLT3-WT), cells with the FLT3 internal tandem duplication (FLT3-ITD) and tyrosine kinase domain mutation (FLT3-TKD) had elevated levels of tyrosine phosphorylated beta-catenin. Although beta-catenin was localized mainly in the cytoplasm in FLT3-WT cells, it was primarily nuclear in FLT3-ITD cells. Treatment with FLT3 kinase inhibitors or FLT3 silencing with RNAi decreased beta-catenin tyrosine phosphorylation and nuclear localization. Conversely, treatment of FLT3 WT cells with FLT3 ligand increased tyrosine phosphorylation and nuclear accumulation of beta-catenin. Endogenous beta-catenin co-immunoprecipitated with endogenous activated FLT3, and recombinant activated FLT3 directly phosphorylated recombinant beta-catenin. Finally, FLT3 inhibitor decreased tyrosine phosphorylation of beta-catenin in leukemia cells obtained from FLT3-ITD-positive AML patients. These data demonstrate that FLT3 activation induces beta-catenin tyrosine phosphorylation and nuclear localization, and thus suggest a mechanism for the association of FLT3 activation and beta-catenin oncogeneic signaling in AML. PMID- 17851560 TI - A simple FISH assay for the detection of 3q26 rearrangements in myeloid malignancy. PMID- 17851561 TI - The JAK2(V617F) mutation may be present several years before the occurrence of overt myeloproliferative disorders. PMID- 17851562 TI - Metabolic syndrome: from global epidemiology to individualized medicine. AB - The metabolic syndrome (MetS) encompasses a constellation of metabolic abnormalities that are thought to place patients at higher risk for the development of diabetes and cardiovascular (CV) disease. The underlying pathophysiology is still a point of contention among various professional organizations leading to inconsistencies in the manner in which MetS is defined. Each definition has its advantages and disadvantages. Nonetheless, there is an agreement that insulin resistance and obesity are likely the central contributing factors. Because the prevalence of obesity has been increasing at a frightening rate in the past few decades, MetS represents a major public health problem that should be identified clinically in individual patients. This review describes the changing epidemiology of obesity and of MetS and discusses its importance in CV disease. We outline the existing controversies that surround MetS and discuss the role of lifestyle, pharmacological, surgical, and novel approaches in its management. PMID- 17851563 TI - IMPDH1 gene polymorphisms and association with acute rejection in renal transplant patients. AB - Inosine 5'-monophosphate dehydrogenase 1 (IMPDH1) catalyzes the rate-limiting step of the de novo pathway for purine synthesis and is a major target of the immunosuppressive drug mycophenolic acid (MPA). Few variants of the IMPDH1 gene have been reported. The objective of this study was to identify and characterize IMPDH1 variants to determine whether genetic variation contributes to differences in MPA response and toxicity in transplant patients. Seventeen genetic variants were identified in the IMPDH1 gene with allele frequencies ranging from 0.2 to 42.7%. In this study, 191 kidney transplant patients who received mycophenolate mofetil were genotyped for IMPDH1. Two single-nucleotide polymorphisms, rs2278293 and rs2278294, were significantly associated with the incidence of biopsy-proven acute rejection in the first year post-transplantation. Future studies of the multifactorial nature of acute rejection must consider IMPDH1 polymorphisms in MPA-treated patients. PMID- 17851564 TI - PK/PD model of indisulam and capecitabine: interaction causes excessive myelosuppression. AB - The anticancer agent indisulam was evaluated in a dose-escalation study in combination with capecitabine. Severe myelotoxicity was observed after multiple treatment cycles. We hypothesized that capecitabine inhibits the synthesis of CYP2C9, which metabolizes indisulam. The objectives were to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the combination treatment and to estimate the impact of a drug-drug interaction on the safety of various dose levels. NONMEM was used to develop a PK/PD model, including the impact of capecitabine coadministration on indisulam pharmacokinetics. A simulation study was performed to evaluate the risk of dose-limiting neutropenia. A time-dependent pharmacokinetic drug-drug interaction resulted in increased exposure to indisulam and in increased myelotoxicity. The risk of dose-limiting neutropenia increased with treatment duration and with dose. The excessive myelosuppression after multiple cycles may be explained by a pharmacokinetic interaction between indisulam and capecitabine. The combination of 550 mg/m(2) indisulam and 1,250 mg/m(2) capecitabine twice daily was considered safe. PMID- 17851565 TI - The effect of herbal medicine baicalin on pharmacokinetics of rosuvastatin, substrate of organic anion-transporting polypeptide 1B1. AB - The aim of this study was to explore potential herb-drug interaction between baicalin and rosuvastatin, a typical substrate for organic anion-transporting polypeptide 1B1 (OATP1B1) related to different OATP1B1 haplotype groups. Eighteen unrelated healthy volunteers who were CYP2C9*1/*1 with different OATP1B1 haplotypes (six OATP1B1*1b/*1b, six OATP1B1*1b/*15, and six OATP1B1*15/*15) were selected to participate in this study. Rosuvastatin (20 mg orally) pharmacokinetics after coadministration of placebo and 50-mg baicalin tablets (three times daily orally for 14 days) were measured for up to 72 h by liquid chromatography-mass spectrometry in a two-phase randomized crossover study. After baicalin treatment, the area under the plasma concentration-time curve (AUC)(0 72) and AUC(0-infinity) of rosuvastatin decreased by 47.0+/-11.0% (P=0.001) and 41.9+/-7.19% (P=0.001) in OATP1B1*1b/*1b, 21.0+/-20.6% (P=0.035) and 23.9+/-8.66% (P=0.004) in OATP1B1*1b/*15, and 9.20+/-11.6% (P=0.077) and 1.76+/-4.89% (P=0.36) in OATP1B1*15/*15, respectively. Moreover, decreases of both AUC(0-72) and AUC(0 infinity) of rosuvastatin among different haplotype groups were significantly different (P=0.002 and <0.001). Baicalin reduces plasma concentrations of rosuvastatin in an OATP1B1 haplotype-dependent manner. PMID- 17851566 TI - CYP2C9 genotype-guided warfarin prescribing enhances the efficacy and safety of anticoagulation: a prospective randomized controlled study. AB - Warfarin anticoagulation effect is characterized by marked variability, some of which has been attributed to CYP2C9 polymorphisms. This study prospectively examines whether a priori knowledge of CYP2C9 genotype may improve warfarin therapy. Patients were randomly assigned to receive warfarin by a validated algorithm ("control", 96 patients) or CYP2C9 genotype-adjusted algorithms ("study", 95 patients). The first therapeutic international normalized ratio and stable anticoagulation were reached 2.73 and 18.1 days earlier in the study group, respectively (P<0.001). The faster rate of initial anticoagulation was driven by a 28% higher daily dose in the study group (P<0.001). Study group patients spent more time within the therapeutic range (80.4 vs 63.4%, respectively, P<0.001) and experienced less minor bleeding (3.2 vs 12.5%, P<0.02, respectively). In conclusion, CYP2C9 genotype-guided warfarin therapy is more efficient and safer than the "average-dose" protocol. Future research should focus on construction of algorithms that incorporate other polymorphisms (VKORC1), host factors, and environmental influences. PMID- 17851568 TI - Molecular medicine hones therapeutic arts to science. PMID- 17851571 TI - Nutraceuticals: miracle or meme? AB - Nutraceuticals, widely becoming adopted as a catchall term to refer to vitamins, minerals, herbs, and various other supplements, continue to gain popularity among large segments of the population, despite little proof of any benefit of most of these compounds. PMID- 17851572 TI - An assessment of direct-to-consumer advertising of prescription drugs. AB - Advertising is widely seen by economists and regulators as beneficial to markets and consumers. The prescription drug market offers exceptional opportunities for direct-to-consumer advertising (DTCA) to provide new-product information, improve compliance, alleviate widespread underdiagnosis and undertreatment, and motivate new-product development.5 DTCA can also induce excess or even dangerous prescribing, however, partly because patients are poorly informed and usually pay far less than the full cost of drugs. Empirical research can help resolve these issues. PMID- 17851573 TI - Direct-to-consumer advertising of prescription drugs: balancing benefits and risks, and a way forward. PMID- 17851574 TI - Drug discovery and development in the age of molecular medicine. AB - Drug discovery might be better termed drug invention. Discoveries take place globally, and many arise from academia and research institutes. The job of the biotechnology and pharmaceutical industry is to identify those that stand the greatest chance of being turned into medicines to improve health-in other words, to invent a practical outcome on the basis of discovery. In this commentary we identify some of the areas in which molecular medicine has had the greatest impact and continues to change the invention of medicines. PMID- 17851575 TI - Beyond genomics. AB - The sequencing of the human genome has already had an enormous impact on medicine, particularly with single-gene changes that predispose to a serious disease such as cystic fibrosis or the overexpression of Her2 in about one-third of breast cancers. Genetic technology has led to some very important therapeutic innovations, including the use of imatinib mesylate (Gleevec) in BCR-ABL chronic myeloid leukemia and of trastuzumab (Herceptin) in Her2-positive breast cancer, but the much anticipated explosion of new effective treatments has been more modest than expected. PMID- 17851576 TI - Targeting cell death. AB - Functional consequences of myocardial or cerebral infarction are the result of excessive cell death. It is patent that preventing cell death is the therapeutic goal in any ischemia-reperfusion setting. Mitochondria amplify apoptotic cascades and have emerged as crucial organelles in ischemia-reperfusion. Changes in mitochondrial inner membrane permeability and in the morphology of the organelle are regulated, perhaps interconnected processes that are starting to emerge as novel therapeutic targets for reducing cell death induced by ischemia reperfusion. PMID- 17851577 TI - Translation of pharmacogenetics into clinically relevant testing modalities. AB - Pharmacogenetics (PGx) relies on the genetic makeup of an individual to predict drug response and efficacy, as well as potential adverse drug events. Significant advances in PGx research have been made since inherited differences in response to such drugs as isoniazid and succinylcholine were explored in the 1950s, and the clinical utility and application of PGx are especially apparent in some subspecialty areas of chemotherapeutic, psychotropic drug, and anticoagulant therapies. PMID- 17851578 TI - Molecular medicine: how, what, and when? AB - Integrating molecular medicine into clinical practice will create many challenges. But the existing genetic testing paradigm may not be the right model for introducing these new technologies. PMID- 17851579 TI - Low hepatic cytochrome P450 3A activity is a risk for corticosteroid-induced osteonecrosis. PMID- 17851581 TI - To study hypoactive sexual desire disorder in a fragile X carrier female successfully treated with local testosterone application. AB - There is still considerable controversy concerning the role of androgen therapy for hypoactive sexual desire disorder in females. Clinical trials have shown that exogenous testosterone therapy improves arousability, sexual desire and fantasy, frequency of sexual activity and orgasm, and satisfaction and pleasure from the sexual act. We report our experience of 36-year-old fragile X carrier female presented to our department with low sex drive and subjectively poor arousal for the past 1 year. We decided to treat her with local testosterone in a pump form (1% 5 g twice a week). She responded very well to the treatment, and in 3 weeks her libido and sexual functions improved dramatically. We decided to continue the same treatment for almost 1 year following up her free and total testosterone, complete lipid profiles, liver functions and complete blood picture every 3 months. During the whole course of treatment, she had mild facial acne, which was resolved in 2 months after completing treatment with testosterone. This is our first and only case of this syndrome with low sexual desire disorder treated with local testosterone in a pump form. Based upon our 1 year follow-up, low-dose testosterone is a safe and effective approach in treating hypoactive sexual desire disorder in a fragile X carrier female, provided the patient is monitored every 3 months for blood counts, lipid profiles, liver functions and free and total testosterone levels. PMID- 17851582 TI - 'Off-label' drug use in sexual medicine treatment. AB - Phosphodiesterase type 5 inhibitors are the only drugs approved for a specific sexual function disorder. All other drugs used in the treatment of sexual disorders are used 'off-label.' This paper reviews the use of drugs in the treatment of premature ejaculation, Peyronie's disease and female hypoactive sexual desire disorder (HSDD). While the treatment of premature ejaculation is quite well documented and supported by evidence of good quality in the medical literature, there is little evidence for the use of the variety of medications in use for the treatment of Peyronie's disease. In particular, the use of verapamil is not supported by any double-blind studies whatsoever. The use of testosterone patch for treatment of HSDD in postmenopausal women is well documented, but not in premenopausal women. PMID- 17851583 TI - Segmental infarction of the testis: an exceptional complication of diabetes microangiopathy. AB - We report a case of segmental infarction of the testis in a 55-year-old man. Past medical history included 12 years of type II diabetes and hypertension. The patient presented with a 2-month history of testicular pain and was found clinically and sonographically to have a testicular tumour. The pathological examination of the partial orchiectomy specimen revealed segmental infarction of the testicle secondary to diabetes microangiopathy. We propose diabetes microangiopathy as a localization and aetiology of segmental testicular infarction. A possible testicular sparing procedure through an inguinal approach may be considered in cases of testicular masses for which the clinical and imaging findings are suggestive of focal testicular infarction. PMID- 17851584 TI - Crucial roles of MZF1 and Sp1 in the transcriptional regulation of the peptidylarginine deiminase type I gene (PADI1) in human keratinocytes. AB - Peptidylarginine deiminases (PADs) catalyze the conversion of protein-bound arginine residues into citrulline residues in a calcium-dependent manner. The PAD1 gene (PADI1) is expressed in a few tissues, including the epidermis, where the protein is detected with a higher level in the more differentiated keratinocytes. Using quantitative reverse transcription-PCR experiments, we show that PADI1 mRNAs are more abundant in keratinocytes cultured with 1.2 than 0.15 mM calcium. We cloned and characterized the promoter region using human keratinocytes transfected with variously deleted fragments of the 5'-upstream region of PADI1 coupled to the luciferase gene. We found that as few as 195 bp upstream from the transcription initiation site were sufficient to direct transcription of the reporter gene. Mutations of MZF1- or Sp1-binding sites markedly reduced PADI1 promoter activity. Chromatin immunoprecipitation assays revealed that MZF1 and Sp1/Sp3 bind to this region in vivo. Furthermore, MZF1 or Sp1 small interfering RNAs (siRNAs) effectively diminished PADI1 expression in keratinocytes cultured in both low- and high-calcium-containing medium. In addition, the expression of MZF1 and PAD1 increased in parallel when normal human epidermal keratinocytes underwent differentiation. These data indicate that MZF1 and Sp1/Sp3 binding to the promoter region drive the PADI1 expression. PMID- 17851585 TI - Phase- and stage-related proportions of T cells bearing the transcription factor FOXP3 infiltrate primary melanoma. AB - Although tumor-infiltrating lymphocytes (TILs) of primary cutaneous melanoma (PCM) include cytolytic T cells able to exert anti-PCM immunity, progression of PCM most frequently occurs, raising the hypothesis that the PCM microenvironment may also exert suppressive forces, for example, possibly developed by regulatory T (T(REG)) lymphocytes. The aim of this study was to investigate whether TILs of PCMs include lymphocytes bearing the transcription factor forkhead box protein P3 (FOXP3), which is the T(REG) lineage specification molecule in mice, and is debated to have a similar role in humans. Fourteen patients with PCM were selected, of which four had radial growth phase (RGP) stage I melanoma, five had vertical growth phase (VGP) stage I melanoma, and five had VGP stage III-IV melanoma. Formalin-fixed, paraffin-embedded sections were utilized for immunohistochemical single and double stainings. TILs of PCMs included FOXP3 bearing lymphocytes, which predominantly were CD20- and CD8-negative, but CD3-, CD4-, and CD25-positive, thus consistent with the standard immunophenotypical characteristics of "natural" T(REG) cells. Further, the proportions of FOXP3 bearing lymphocytes were higher in vertical than in RGP (P=0.001), as well as in late than in early melanoma stages (P<0.001). Should these FOXP3-bearing lymphocytes actually exert regulatory capabilities within the PCM microenvironment, they may suppress "in vivo" the local anti-PCM immune response, thus favoring melanoma progression. PMID- 17851586 TI - Five new CYLD mutations in skin appendage tumors and evidence that aspartic acid 681 in CYLD is essential for deubiquitinase activity. AB - Brooke-Spiegler syndrome, familial cylindromatosis, and familial trichoepithelioma are autosomal-dominant genetic predispositions for benign tumors of skin appendages caused by mutations in the CYLD gene localized on chromosome 16q12-q13. The encoded protein functions as ubiquitin-specific protease (UBP), which negatively regulates NF-kappaB and c-Jun N-terminal kinase (JNK) signaling. We investigated five families affected with these skin neoplasms and identified four premature stop codons and the novel missense mutation D681G in a family in which 11 of 12 investigated tumors were trichoepitheliomas. CYLD protein harboring this missense mutation had a significant reduced ability to inhibit TNF receptor-associated factor (TRAF)2- and TRAF6-mediated NF-kappaB activation, tumor necrosis factor-alpha (TNFalpha)-induced JNK signaling, and to deubiquitinate TRAF2. CYLD-D681G was coimmunoprecipitated by TRAF2, but was unable to cleave K63-linked polyubiquitin chains. Aspartic acid 681 is highly conserved in CYLD homologues and other members of the UBP family, but does not belong to the Cys and His boxes providing the CYLD catalytic triad (Cys601, His871, and Asp889). As reported previously, the homologous residue D295 of HAUSP/USP-7 forms a hydrogen bond with the C-terminal end of ubiquitin and is important for the enzymatic activity. These results underline that D681 in CYLD is required for cleavage of K63-linked polyubiquitin chains. PMID- 17851587 TI - Mice expressing a mutant Krt75 (K6hf) allele develop hair and nail defects resembling pachyonychia congenita. AB - KRT75 (formerly known as K6hf) is one of the isoforms of the keratin 6 (KRT6) family located within the type II cytokeratin gene cluster on chromosome 12 of humans and chromosome 15 of mice. KRT75 is expressed in the companion layer and upper germinative matrix region of the hair follicle, the medulla of the hair shaft, and in epithelia of the nail bed. Dominant mutations in members of the KRT6 family, such as in KRT6A and KRT6B cause pachyonychia congenita (PC) -1 and 2, respectively. To determine the function of KRT75 in skin appendages, we introduced a dominant mutation into a highly conserved residue in the helix initiation peptide of Krt75. Mice expressing this mutant form of Krt75 developed hair and nail defects resembling PC. This mouse model provides in vivo evidence for the critical roles played by Krt75 in maintaining hair shaft and nail integrity. Furthermore, the phenotypes observed in our mutant Krt75 mice suggest that KRT75 may be a candidate gene for screening PC patients who do not exhibit obvious mutations in KRT6A, KRT6B, KRT16, or KRT17, especially those with extensive hair involvement. PMID- 17851589 TI - Human embryonic stem cells create their own niche. PMID- 17851588 TI - Metabolic enzymes link morphine withdrawal with metabolic disorder. PMID- 17851590 TI - Responses to Drs. Kim and Dionne regarding comments on Diatchenko, et al. Catechol-O-methyltransferase gene polymorphisms are associated with multiple pain evoking stimuli. Pain 2006; 125: 216-24. PMID- 17851591 TI - Energetics and kinetics of vacancy diffusion and aggregation in shocked aluminium via orbital-free density functional theory. AB - A possible mechanism for shock-induced failure in aluminium involves atomic vacancies diffusing through the crystal lattice and agglomerating to form voids, which continue to grow, ultimately resulting in ductile fracture. We employ orbital-free density functional theory, a linear-scaling first-principles quantum mechanics method, to study vacancy formation, diffusion, and aggregation in aluminium under shock loading conditions of compression and tension. We calculate vacancy formation and migration energies, and find that while nearest-neighbor vacancy pairs are unstable, next-nearest-neighbor vacancy pairs are stable. As the number of nearby vacancies increases, we predict that vacancy clusters preferentially grow through next-nearest-neighbor vacancies. The energetics are found to be greatly affected by expansion and compression, leading to insight as to how vacancies behave under shock conditions. PMID- 17851592 TI - Single-colloidal-particle microcontact printing. AB - We have utilized colloidal probe atomic force microscopy (AFM) in conjunction with microinterferometry to study the forces acting in the microcontact printing process. The procedure we have developed yields well defined asymmetric imprints on colloidal probes, which could find further application in interaction force measurements between Janus-type particles and surfaces. PMID- 17851593 TI - FTIR spectroscopy combined with quantum chemical calculations to investigate adsorbed nitrate on aluminium oxide surfaces in the presence and absence of co adsorbed water. AB - Surface reactions of nitrogen oxides with aluminium oxide particles result in the formation of adsorbed nitrate. Specifically, when alpha-Al(2)O(3) and gamma Al(2)O(3) particles are exposed to gas-phase NO(2) and HNO(3) adsorbed nitrate forms on the surface. In this study, Fourier transform infrared (FTIR) spectroscopy is combined with quantum chemical calculations to further our understanding of the adsorbed nitrate product on aluminium oxide particle surfaces in the presence and absence of co-adsorbed water at 296 K. FTIR spectra of adsorbed nitrate on alpha-Al(2)O(3) and gamma-Al(2)O(3) particles are interpreted using calculated vibrational frequencies of nitrate coordinated to binuclear Al oxide cluster models. Comparison of the calculated and experimental vibrational frequencies of adsorbed nitrate establishes different modes of coordination (monodentate, bidentate and bridging) of the nitrate ion to the surface in the absence of adsorbed water. In the presence of co-adsorbed water, the nitrate ion becomes fully solvated, as shown by a comparison of the experimental nitrate infrared spectra as a function of relative humidity with the calculated nitrate vibrational frequencies for binuclear Al cluster compounds which contain both coordinated nitrate ions and water molecules. These calculations also suggest that adsorbed water can displace nitrate from direct coordination to the surface, leading to an outer-sphere nitrate adsorption complex as well as an inner-sphere complex. Furthermore, the relative humidity dependence of the spectra suggest that water does not evenly wet the surface even at high relative humidity, as there are open or bare surface sites where nitrate ions are not solvated. Besides adsorbed mondendate, bidendate, bridging and solvated nitrate, the presence of ion bound nitrate ion, partially solvated nitrate, molecular nitric acid, hydronium ion and H(3)O(+):NO(3)(-) ion pairs on the oxide surface are also discussed. PMID- 17851594 TI - Supersonic jet studies of solvation effects on the spectroscopy and photophysics of 4-diethylaminopyridine. AB - We present the results of spectroscopic and photophysical investigations of 4 diethylaminopyridine (DEAP) and its 1 : 1 complexes with a number of protic solvents such as water and various alcohols of different acidity isolated under supersonic jet conditions. While a double resonance vibrational spectroscopic method was employed to investigate the size and geometrical structure of jet cooled clusters, laser-induced fluorescence spectroscopy was used to examine the changes of photophysics induced by complexation of DEAP with solvent molecule(s). The results obtained from ab initio calculations enable the assignment of geometries and of the vibrational spectra of the clusters in the OH-stretch region. The comparison of the experimental and calculated vibrational spectra indicates that the solvent molecule is hydrogen-bonded to the pyridine nitrogen atom. Dual luminescence is observed only for the complexes with alcohols of relatively strong acidity. PMID- 17851595 TI - FTIR spectroscopy and thermodynamics of hydrogen adsorbed in a cross-linked polymer. AB - The adsorption of H(2) in a cross-linked poly(styrene-co-divinylbenzene) (St-DVB) microporous polymer (BET surface area 920 m(2) g(-1)) is studied by volumetric and gravimetric methods, FTIR spectroscopy at variable temperature (300-14 K) and ab initio calculations. At 77 K the polymer reversibly stores up to 1.3 mass% H(2) at a pressure of 1 bar and 1.8 mass% at 10 bar. The adsorption process involves the specific interaction of H(2) with the structural phenyl rings through weak dispersive forces. The interacting molecules become IR active and give rise to vibrational and rotational-vibrational manifestations which are affected by the temperature, the contact time and the H(2) equilibrium pressure. The spectra of the H(2)/St-DVB system reported here represent the first IR evidence of the adsorption of hydrogen on unsaturated molecules. The adsorption enthalpy is evaluated by the VTIR (variable temperature IR spectroscopy) method (C. Otero Arean et al., Phys. Chem. Chem. Phys., 2007, DOI: 10.1039/b615535a) and compared with the results of ab initio calculations for the H(2)/benzene interaction and with literature data. PMID- 17851596 TI - Benchmark RI-MP2 database of nucleic acid base trimers: performance of different density functional models for prediction of structures and binding energies. AB - A new database of nucleic acid base trimers has been developed that includes 141 geometries and stabilization energies obtained at the RI-MP2 level of theory with the TZVPP basis set. Compared to previously compiled biologically oriented databases, this new construct includes considerably more complicated structures; the various intermolecular interactions in the trimers are quite heterogeneous and in particular include simultaneous hydrogen bonding and stacking interactions, which is similar to the situation in actual biopolymers. Validation against these benchmark data is therefore a more demanding task for approximate models, since correct descriptions of all energy terms are unlikely to be accomplished by fortuitous cancellations of systematic errors. The density functionals TPSS (both with and without an empirical dispersion term), PWB6K, M05 2X, and BH&H, and the self-consistent charge density functional tight binding method augmented with an empirical dispersion term (SCC-DFTB-D) were assessed for their abilities accurately to compute structures and energies. The best reproduction of the BSSE corrected RI-MP2 stabilization energies was achieved by the TPSS functional (TZVPP basis set) combined with empirical dispersion; removal of the dispersion correction leads to significantly degraded performance. The M05 2X and PWB6K functionals performed very well in reproducing the RI-MP2 geometries, but showed a systematic moderate underestimation of the magnitude of base stacking interactions. The SCC-DFTB-D method predicts geometries in fair agreement with RI-MP2; given its computational efficiency it represents a good option for initial scanning of analogous biopolymeric potential energy surfaces. BH&H gives geometries of comparable quality to the other functionals but significantly overestimates interaction energies other than stacking. PMID- 17851597 TI - Laser-operated chiral molecular switch: quantum simulations for the controlled transformation between achiral and chiral atropisomers. AB - We report quantum dynamical simulations for the laser controlled isomerization of 1-(2-cis-fluoroethenyl)-2-fluorobenzene based on one-dimensional electronic ground and excited state potentials obtained from (TD)DFT calculations. 1-(2-cis fluoroethenyl)-2-fluorobenzene supports two chiral and one achiral atropisomers, the latter being the most stable isomer at room temperature. Using a linearly polarized IR laser pulse the molecule is excited to an internal rotation around its chiral axis, i.e. around the C-C single bond between phenyl ring and ethenyl group, changing the molecular chirality. A second linearly polarized laser pulse stops the torsion to prepare the desired enantiomeric form of the molecule. This laser control allows the selective switching between the achiral and either the left- or right-handed form of the molecule. Once the chirality is "switched on" linearly polarized UV laser pulses allow the selective change of the chirality using the electronic excited state as intermediate state. PMID- 17851598 TI - Thermal effect on C-H stretching vibrations of the imidazolium ring in ionic liquids. AB - We have studied temperature dependent IR spectra of the C-H stretching modes of the imidazolium ring in [bmim][PF(6)], [bmim][Tf(2)N], [emim][Tf(2)N], [hmim][Tf(2)N], and [bmim][BF(4)]. Temperatures in this study are from 278 to 348 K at an interval of 10 K. Spectra of the C-H stretching modes have been deconvoluted using our previous computer program of the Voigt-lineshape function. Frequency shifts, Lorentzian spectral widths, and band absorbance were examined as a function of temperature. In order to interpret the observed behaviors, we have developed a simple mechanical model as well as a chemical equilibrium model. The model analyses suggest that enthalpy changes for the cluster and/or ion-pair breaking reactions in the liquid state are several kJ mol(-1) endothermic, and the degree of dissociations of ion pairs or hydrogen bonded clusters is in the range from 0.3 to 0.9 with different magnitudes for the five ionic liquids. PMID- 17851599 TI - Spectroscopic properties of trichlorofluoromethane CCl(3)F calculated by density functional theory. AB - Density functional theory is used to generate local potential energy surfaces in normal coordinates for several chlorine isotopomers of trichlorofluoromethane (CCl(3)F, CFC11). An examination of predicted structures suggested that the PBE0 functional would be suitable. Anharmonic surfaces around the equilibrium geometries are reported, as determined by energies, gradients, and second derivatives. Vibrational levels for fundamentals, overtones and combination bands are reported, as well as harmonic frequencies, anharmonic constants, rotational constants, isotope shifts, and infrared intensities. These are compared with experimental information. PMID- 17851600 TI - Reaction of phenylperoxy radicals with NO(2) at 298 K. AB - In the present work, phenylperoxy radicals were generated by stationary 254 nm photolysis of iodobenzene and nitrosobenzene in the presence of O(2) and NO(2) at 298 K and a total pressure of 1 bar (M = N(2)). Experiments were performed on time scales of seconds or minutes in a temperature controlled photoreactor made of quartz (v = 209 L). Major gas phase products identified and quantified in situ by long-path IR absorption include N(2)O(5), NO, HONO, HNO(3), CO, and o nitrophenol. In addition, evidence is presented for the formation of an aerosol consisting of p-nitrophenol. The occurrence of N(2)O(5) as a major product in both reaction systems, the strong loss of NO(2) in the iodobenzene system and the comparison of measured product distributions with the results of numerical model calculations suggest that the reaction C(6)H(5)O(2) + NO(2) --> C(6)H(5)O + NO(3), k(5)occurs in both photolysis systems, a major part of the NO(3) being scavenged as N(2)O(5). The results of ab initio calculations imply that proceeds via a short-lived peroxynitrate intermediate. In the photolysis of nitrosobenzene NO(2)-O(2)-N(2) mixtures, NO and NO(2) compete for C(6)H(5)O(2) radicals. Comparison of measured and modelled product distributions allows to set a lower limit of k(5) > 1 x 10(-12) cm(3) molecule(-1) s(-1) at 298 K. This lower limit is consistent with the assumption that k(5) is equal to the high pressure recombination rate constant of RO(2) + NO(2) --> RO(2)NO(2) reactions, i.e. with k(5) approximately 7 x 10(-12) cm(3) molecule(-1) s(-1) at 298 K, 1bar. PMID- 17851601 TI - Advances on the nanostructuration of magnetic molecules on surfaces: the case of single-molecule magnets (SMM). AB - SMMs exhibit slow magnetization relaxation rates characteristic of nanodomain particles whose origin is however on individual molecules. For this reason, they have attracted much interest due to their potential applications in high-density information storage devices and quantum computing applications, where for instance, each molecule can be used as a magnetic bit of information. However, for this to become a reality, several basic studies such as their deposition on surfaces are still highly required. Here we will revise all the experimental approximations that have been so far reported for their addressing, nanostructuration and study on surfaces, from the use of stamps as templates to their anchorage to gold surface through the use of thiol-based ligands. It is also important to emphasize that the results and methodologies described along this review are applicable not only to SMMs but to any molecular material. PMID- 17851602 TI - Hydroxyquinolines with extended fluorophores: arrays for turn-on and ratiometric sensing of cations. AB - 8-Hydroxyquinoline-based ligands with extended conjugated fluorophores were designed to provide turn-on and ratiometric signal output optimized for use in fluorescence-based sensor arrays, where the changes in blue and green channels of the RGB signal are used to distinguish between cationic analytes. PMID- 17851603 TI - Configurationally stable propeller-like triarylphosphine and triarylphosphine oxide. AB - Configurationally stable, propeller-like triarylphosphine and triarylphosphine oxide can be synthesized; a chiral scaffold based on Lissoclinum-cyclopeptides linked via three peptide bonds with a triphenylphosphine and triphenylphosphine oxide moiety, respectively, prevents effectively epimerization at the chiral phosphorus atom. PMID- 17851604 TI - Novel application of Leuckart-Wallach reaction for synthesis of tetrahydro-1,4 benzodiazepin-5-ones library. AB - A novel and efficient strategy has been developed to synthesize privileged tetrahydro-1,4-benzodiazepines with excellent yields and purities; this synthetic pathway was established by the revitalization of the Leuckart-Wallach (LW) reaction via solid-phase synthesis. PMID- 17851605 TI - Binding of an acetonitrile molecule inside the ethereal cavity of a hexaarylbenzene-based receptor via a synergy of C-H...O/C-H...pi interactions. AB - A pair of hexaarylbenzene-based receptors, which contain a circular, as well as a partially-broken, ethereal fence around the central benzene ring, bind acetonitrile molecules via a synergy of C-H...O and C-H...pi interactions, as probed by X-ray crystallography. PMID- 17851606 TI - Template-free method to prepare polymer nanocapsules embedded with noble metal nanoparticles. AB - In this paper, polymer nanocapsules embedded with noble metal nanoparticles and showing a good catalytic activity were prepared by a novel and convenient method. PMID- 17851607 TI - A reversible metal-ligand bond break associated to a spin-crossover. AB - The [Fe(II)L(CN)(2)].H(2)O complex, dicyano[2,13-dimethyl-6,9-dioxa-3,12,18 triazabicyclo[12.3.1]octadeca-1(18),2,12,14,16-pentaene]iron(II) monohydrate, exhibits a thermal induced metal-ligand bond break reversible in the solid state and associated to a spin crossover that corresponds to an unprecedented structurally characterized modification of the coordination metal environment from a hepta-coordinate high spin state to a hexa-coordinate low spin state. PMID- 17851608 TI - A dual near-infrared pH fluorescent probe and its application in imaging of HepG2 cells. AB - A dual near-infrared pH fluorescent probe has been designed, synthesized and applied to HepG2 cells, with a pK(a) value of 5.14 under acidic conditions and 11.31 under basic conditions, which is valuable for studying acidic organelles in living cells and pH changes in chemical systems. PMID- 17851610 TI - Threaded structure and blue luminescence of (CuCN)20(Piperazine)7. AB - The structurally unique and highly luminescent 20 : 7 complex of CuCN with piperazine (Pip) was formed under aqueous conditions; its structure reveals two interpenetrated 2D sub-networks in 6 : 1 ratio: (CuCN)2(Pip) and (CuCN)8(Pip), the latter consisting of Cu18(CN)16(Pip)2 macrocycles. PMID- 17851609 TI - Simple and rapid colorimetric enzyme sensing assays using non-crosslinking gold nanoparticle aggregation. AB - Non-crosslinking gold nanoparticle (AuNP) aggregation induced by the loss (or screen) of surface charges is applied for enzymatic activity sensing and potentially inhibitor screening. PMID- 17851611 TI - Simple and sensitive aptamer-based colorimetric sensing of protein using unmodified gold nanoparticle probes. AB - We describe herein simple and sensitive aptamer-based colorimetric sensing of protein (alpha-thrombin in this work) using unmodified gold nanoparticle probes. PMID- 17851612 TI - A shape-dependent hydrophobic effect for tetrazoles. AB - An adaptive tetrazole-derived host provides insight into tetrazolate-biomolecule interactions, and is the first member of a new family of receptors that function in pure water. PMID- 17851613 TI - Phenothiazine derivatives for efficient organic dye-sensitized solar cells. AB - Novel organic dyes based on the phenothiazine (PTZ) chromophore were designed and synthesized for dye-sensitized solar cells, which give solar energy-to electricity conversion efficiency (eta) of up to 5.5% in comparison with the reference Ru-complex (N3 dye) with an eta value of 6.2% under similar experimental conditions. PMID- 17851614 TI - Unprecedented (3,4)-connected metal-organic frameworks (MOFs) with 3-fold interpenetration and considerable solvent-accessible void space. AB - Via solvothermal synthesis, the self-assembly of CuCl(2), 1,3,5 benzenetricarboxylic acid, and N,N'-bis(4-pyridylformamide)-1,4-benzene in DMF generated a novel coordination polymer containing an unprecedented (3,4) connected network; 3-fold interpenetration and considerable solvent-accessible cavities occupied by reversible guest water molecules were also observed. PMID- 17851615 TI - Glycosidase inhibitors as conformational transition state analogues. AB - A method for estimating the conformational similarity between hexopyranose rings is presented and used to probe the behaviour of various glycosyl hydrolase inhibitors as conformational transition state analogues. PMID- 17851616 TI - Facile synthesis of silver nano/micro-ribbons or saws assisted by polyoxomolybdate as mediator agent and vanadium(IV) as reducing agent. AB - Original and effective syntheses of crystalline silver wires and saw bundles, using reduced Keggin polyoxomolybdovanadate (POM) as mediator and reducing agent, were performed in acetonitrile at room temperature; several parameters influencing the final silver 1D-structures, with micrometric length and nanometric thickness, were varied: the nature of the POM, silver salts, vanadium(iv) source and the mild conditions. PMID- 17851617 TI - Encapsulation of titanium(IV) oxide particles in hollow silica for size-selective photocatalytic reactions. AB - A core-shell composite of TiO2 particles encapsulated in a hollow silica was fabricated, and the core-shell composite showed size-selective photocatalytic activity for decomposition of organics without reducing the intrinsic activity of the naked TiO2 core. PMID- 17851618 TI - A novel cyclization reaction between 2,3-bis(trimethylsilyl)buta-1,3-diene and acyl chlorides with straightforward formation of polysubstituted furans. AB - A novel cyclization process of 2,3-bis(trimethylsilyl)buta-1,3-diene with various acyl chlorides in the presence of aluminium trichloride affords 2,5-disubstituted or 2,3,5-trisubstituted furans in short reaction time; a subsequent acylation process of the furan ring occurs if the reaction time is prolonged. PMID- 17851619 TI - Mild lanthanide(III) catalyzed formation of 4,5-diaminocyclopent-2-enones from 2 furaldehyde and secondary amines: a domino condensation/ring opening/electrocyclization process. AB - Lewis acid catalyzed reaction of 2-furaldehyde and secondary amines results in the formation of 4,5-diaminocyclopent-2-enones exclusively as the trans diastereomers: computational studies support the stereochemistry of the adducts as arising from a thermal conrotatory pi4a electrocyclization of an initial ring opened intermediate (a deprotonated Stenhouse salt). PMID- 17851620 TI - Multifunctionalised cationic fullerene adducts for gene transfer: design, synthesis and DNA complexation. AB - Cationic poly-N,N-dimethylfulleropyrrolidinium derivatives have been designed and synthesised to complex plasmid DNA for gene delivery. PMID- 17851621 TI - N-Methyl substituted 2',4'- BNANC: a highly nuclease-resistant nucleic acid analogue with high-affinity RNA selective hybridization. AB - Oligonucleotides modified with a novel BNA analogue, 2', 4'-BNA(NC)[N-Me], were synthesized, and in comparison to 2',4'-BNA (LNA), have similarly high RNA affinity, better RNA selectivity and much higher resistance to nuclease degradation, suggesting that the novel BNA analogue may be particularly useful for antisense approaches. PMID- 17851622 TI - Linear, redox modified DNA probes as electrochemical DNA sensors. AB - We show here that hybridization-linked changes in the dynamics of a redox modified, electrode-bound linear (as opposed to stem-loop) probe DNA produce large changes in Faradaic current, allowing for the ready detection of target oligonucleotides. PMID- 17851623 TI - Highly recoverable pyridinium-tagged Hoveyda-Grubbs pre-catalyst for olefin metathesis. Design of the boomerang ligand toward the optimal compromise between activity and reusability. AB - Whereas the boomerang ligand of Hoveyda-Grubbs pre-catalysts can be modified by attachment of a pyridinium tag to its benzylidene moiety, a precise adjustment of the length of the spacer allows the optimum balance to be reached between the activity of the catalyst and its recoverability, exceeding 98% after 6 catalytic runs in the best case. PMID- 17851624 TI - Efficient synthetic routes to aromatic compounds using ring-closing olefin metathesis followed by dehydration, oxidation, and tautomerization. AB - A simple synthetic approach to aromatic compounds using combinations of RCM, dehydration, oxidation, and tautomerization is described. PMID- 17851625 TI - Surface modification of gold nanorods with synthetic cationic lipids. AB - Colloidal gold nanorods (GNRs), which were passivated with cationic cerasome forming lipids having triethoxysilyl groups, were obtained in the aqueous phase by sonication of the mixture of lipids and GNRs. PMID- 17851626 TI - Reusable, label-free electrochemical aptasensor for sensitive detection of small molecules. AB - We report a sensitive electrochemical aptasensor for adenosine based on electrochemical impedance spectroscopy measurement, which gives not only a label free but also a reusable platform to make the detection of small molecules simple and convenient. PMID- 17851627 TI - Ameliorating effect of chloride on nitrite toxicity to freshwater invertebrates with different physiology: a comparative study between amphipods and planarians. AB - High nitrite concentrations in freshwater ecosystems may cause toxicity to aquatic animals. These living organisms can take nitrite up from water through their chloride cells, subsequently suffering oxidation of their respiratory pigments (hemoglobin, hemocyanin). Because NO(2)(-) and Cl(-) ions compete for the same active transport site, elevated chloride concentrations in the aquatic environment have the potential of reducing nitrite toxicity. Although this ameliorating effect is well documented in fish, it has been largely ignored in wild freshwater invertebrates. The aim of this study was to compare the ameliorating effect of chloride on nitrite toxicity to two species of freshwater invertebrates differing in physiology: Eulimnogammarus toletanus (amphipods) and Polycelis felina (planarians). The former species presents gills (with chloride cells) and respiratory pigments, whereas in the latter species these are absent. Test animals were exposed in triplicate for 168 h to a single nitrite concentration (5 ppm NO(2)-N for E. toletanus and 100 ppm NO(2)-N for P. felina) at four different environmental chloride concentrations (27.8, 58.3, 85.3, and 108.0 ppm Cl(-)). The number of dead animals and the number of affected individuals (i.e., number of dead plus inactive invertebrates) were monitored every day. LT(50) (lethal time) and ET(50) (effective time) were estimated for each species and each chloride concentration. LT(50) and ET(50) values increased with increases in the environmental chloride concentration, mainly in amphipods. Results clearly show that the ameliorating effect of chloride on nitrite toxicity was more significant in amphipods than in planarians, likely because of the absence of gills (with chloride cells) and respiratory pigments in P. felina. Additionally, this comparative study indicates that the ecological risk assessment of nitrite in freshwater ecosystems should take into account not only the most sensitive and key species in the communities, but also chloride levels in the aquatic environment. PMID- 17851628 TI - B-natriuretic peptide: a helpful clinical marker after Norwood I. AB - Amplified cardiac B-natriuretic peptide (BNP) expression results from ventricular volume or pressure overload. Clinicians have used BNP levels when evaluating cardiac performance in patients with varied clinical conditions. We report a case in which BNP levels helped guide early catheterization intervention in a patient after stage 1 Norwood palliation. PMID- 17851629 TI - Giant coronary aneurysms in Kawasaki disease. PMID- 17851630 TI - Correlation between peripheral and central venous pressures in children with congenital heart disease. AB - Central venous pressure (CVP) measurement is a reliable method for evaluating intravascular volume status and cardiac function, but it is an invasive method that results in some complications such as arterial puncture, pneumothorax, and development of infection. The current study was performed to compare CVP measurements between central and peripheral catheters in infants and children with congenital heart disease referred for right-sided heart catheterization. The CVP and peripheral venous pressure (PVP) in 45 patients were measured simultaneously. The mean difference between CVPs measured from the central and peripheral catheters was 8 +/- 4 cm H(2)O. The linear regression equation showed that CVP = 0.32 PVP + 3.8 (r = 0.67; p < 0.005). There was no difference in CVP measurements depending on the intravenous cannula and chest diameters, arm diameter, arm length, body surface area, patient's age (< or =10 years and >10 years), and type of congenital heart disease (cyanotic or noncyanotic). In conclusion, although CVP measured from a peripheral intravenous catheter in infants and children with congenital heart disease is not as accurate as the measurement in adults, the aforementioned linear regression equation based on measurement of PVP gives a reliable estimate of CVP. PMID- 17851631 TI - Ultrasound-guided versus landmark-guided femoral vein access in pediatric cardiac catheterization. AB - BACKGROUND: This study aimed to evaluate whether an ultrasound-guided technique can improve upon a landmark-guided technique in achieving femoral vein access in pediatric cardiac catheterization. METHODS: This study examined 87 consecutive subjects with a median age of 2 years (range, 1 month to 19 years) who had congenital or other heart disease. Femoral vein puncture was attempted using either an ultrasound-guided technique (US group, n = 43) or a landmark-guided technique (LM group, n = 44). The patients were assigned alternately to either an ultrasound- or landmark-guided group. Overall success and traumatic complication rates were compared between the two groups, as well as the influence of patient size and age. RESULTS: The overall rate of success in achieving femoral vein access did not differ between the two groups. Among the successful cases in the two groups, there were no significant differences in patient size or age. Inadvertent femoral artery puncture occurred with 3 (7%) of 43 patients in the US group and with 14 (31.8%) of 44 patients in the LM group, for a significantly higher complication rate in the LM group (p < 0.01). CONCLUSIONS: Ultrasound guided access to the femoral vein minimizes the complication of inadvertent arterial puncture as compared with the landmark-guided approach. PMID- 17851632 TI - Documented transient third-degree atrioventricular block and asystole in a child with familial dysautonomia. AB - An 11-year-old boy with familial dysautonomia presented with palpitations. Continuous 24-h Holter monitoring revealed intermittent high-grade atrioventricular block and asystole. The unopposed parasympathetic tone in patients with dysautonomia may make them susceptible to bradycardia and atrioventricular block. We recommend routine 24-h Holter monitoring screening and, when indicated, consideration of pacemaker implantation to reduce the high risk of sudden death phenomena in this patient population. PMID- 17851633 TI - Not all symptoms disappear after vascular ring division: a pathophysiological interpretation. AB - Vascular rings are a group of cardiovascular lesions due to faulty embryological development derived from an abnormality of neural crest cells (cephalic neurocristopathy). In addition to peculiar symptoms due to compression on the trachea and/or the esophagus, patients with vascular rings might present further features of neural crest-related defects. We report on a case of a child with complete vascular ring, affected both by compressive symptoms and by autonomic disturbances and minor facial anomalies. The autonomic disturbances are clinical features of maturational dysautonomia and tend to disappear with aging, whereas major compressive symptoms are solved by surgery. PMID- 17851634 TI - Morphometric study of the shoulder and subclavicular innervation by the intermediate and lateral branches of supraclavicular nerves. AB - BACKGROUND: The supraclavicular (intermediate) and supra-acromial (lateral) branches of supraclavicular nerves contribute to the innervation of the thorax, shoulder, and neck. Despite their clinical and surgical interest, they are not often considered for descriptive anatomy. The goal of this work was to clarify the morphometric knowledge of these two branches and to discuss the clinical relevance of the anatomical features. METHODS: Intermediate and lateral branches of supraclavicular nerves of 14 necks (8 embalmed cadavers) were dissected using magnifying glasses. Macroscopic parameters were measured and nerve relationships were recorded. RESULTS: In 12 cases, the intermediate and lateral branches arose from a common trunk behind the posterior border of the sternocleidomastoideus muscle, at a mean distance of 96 mm (70-137) from the sternal angle. The intermediate branch divided into two or three secondary rami. Its most internal ramus crossed the middle third of the clavicle and its most external ramus crossed the second lateral quarter of the bone. The distance between the two farthest nerve endings of this branch was at mean of 98 mm (85-125). The mean distance of the most distal nerve ending from the clavicle was 46 mm (30-63). The lateral branch divided into two or three rami in eight cases and did not divide in six cases. Its most anterior rami crossed the trapezius muscle at a mean distance from the clavicular insertion of 17 mm (12-24). In 13 cases, these rami ended posteriorly or at the level of the anterior border of the acromion process and in 12 cases, they ended laterally or at the level of the acromion process with a mean distance 10.4 mm (0-24). CONCLUSION: In case of deficiency of these nerves, pain or sensitive deficit can occur without motor trouble. The factors of acute or chronic injury are direct compression, nerve stretching, repetitive stresses, and direct wound. Moreover, several neck or shoulder surgical approaches are dangerous for these nerves. PMID- 17851635 TI - Both endogenous and exogenous ACh plays antinociceptive role in the hippocampus CA1 of rats. AB - The present study examines the effect of acetylcholine (ACh), muscarinic acetylcholine receptors (mAChRs) agonist pilocarpine and mAChRs antagonist atropine on the pain-evoked response of pain-excited neurons (PEN) and pain inhibited neurons (PIN) in the hippocampal CA1 of rats. The trains of electric impulses applied to the sciatic nerve were used as noxious stimulation. The discharges of PEN and PIN in the hippocampal CA1 were recorded by glass microelectrode. The results showed that intrahippocampal microinjection of ACh (2 microg/1 microl) or pilocarpine (2 microg/1 microl) decreased the frequency of discharge of PEN, and increased the frequency of discharge of PIN evoked by the noxious stimulation in the hippocampal CA1, while intrahippocampal administration of atropine (0.5 microg/1 microl) produced opposite response. On the basis of the above findings, we can deduce that ACh and mAChRs are involved in the modulation of nociceptive information transmission in the hippocampal CA1. PMID- 17851636 TI - U7 snRNA-mediated correction of aberrant splicing caused by activation of cryptic splice sites. AB - A considerable fraction of mutations associated with hereditary disorders and cancers affect splicing. Some of them cause exon skipping or the inclusion of an additional exon, whereas others lead to the inclusion of intronic sequences or deletion of exonic sequences through the activation of cryptic splice sites. We focused on the latter cases and have designed a series of vectors that express modified U7 small nuclear RNAs (snRNAs) containing a sequence antisense to the cryptic splice site. Three cases of such mutation were investigated in this study. In two of them, which occurred in the PTCH1 and BRCA1 genes, canonical splice donor sites had been partially impaired by mutations that activated nearby intronic cryptic splice donor sites. Another mutation found in exonic region in CYP11A created a novel splice donor site. Transient expression of the engineered U7 snRNAs in HeLa cells restored correct splicing in a sequence-specific and dose dependent manner in the former two cases. In contrast, the third case, in which the cryptic splice donor site in the exonic sequence was activated, the expression of modified U7 snRNA resulted in exon skipping. The correction of aberrant splicing by suppressing intronic cryptic splice sites with modified U7 is expected be a promising alternative to gene replacement therapy. PMID- 17851639 TI - 9th National Conference on Anticoagulant Therapy. Preface. PMID- 17851637 TI - A multicenter phase II trial of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine) and gemcitabine in advanced non-small-cell lung cancer with pharmacokinetic evaluation using peripheral blood mononuclear cells. AB - BACKGROUND: We tested the hypothesis that 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine) may enhance response to re-treatment with gemcitabine by enhancing intracellular uptake of gemcitabine in a phase II study. METHOD: Patients who had prior exposure to gemcitabine as a first-line treatment of advanced non-small-cell lung cancer (NSCLC) were given weekly infusions of 3 AP and gemcitabine for 3 weeks followed by 1 week of rest, repeated every 28 days. Plasma and peripheral blood mononuclear cells (PBMCs) were collected to evaluate the effect of 3-AP on pharmacokinetics and intracellular uptake of gemcitabine. RESULT: Twelve patients were treated with a median of two treatment cycles without objective response, hence the study was terminated at interim analysis. Four patients had stable disease and the median time to progression was 3 months (95% confidence interval, CI: 1.7 to 9.1 months). Grade 3 toxicities included neutropenia (two patients), hypoxia (three patients) and dyspnea (one patient). Four patients developed reversible symptomatic methemoglobinemia during 3-AP infusion, with mild to moderately elevated methemoglobin levels that ranged from 7.8 to 17.6% of the total hemoglobin concentration. Limited pharmacokinetic data did not suggest any clinically relevant pharmacological influence of 3-AP on gemcitabine. CONCLUSION: 3-AP did not enhance clinical response to gemcitabine in this cohort of patients with prior exposure to gemcitabine for advanced NSCLC. Further development of 3-AP in lung cancer is challenged by its potential of causing methemoglobinemia and hypoxia, which could be problematic in patients with compromised pulmonary reserves. PMID- 17851638 TI - Pharmacological evaluation of C-3 modified Betulinic acid derivatives with potent anticancer activity. AB - In vitro and in vivo pharmacological screening of Betulinic acid (BA) and five dihydro-BA derivatives modified at C-3 position [4-nitrobenzyl-oximino (1), 2-4 difluoro-benzoyloxy (2), 2-4-difluoro-benzylidene-amino (3), benzoyl-hydrazono (4), and 4-fluorophenyl-hydrazono (5)], having potent in vitro anti-cancer activity was carried out using ADME, animal PK and tumor studies. We found that BA and the derivatives had poor aqueous solubility (<0.1 microg/ml), low to moderate permeability (log Pe<-5.0) and high plasma protein binding (>70%). Although BA and 5 were metabolized by human liver microsomes, derivatives 1, 2, 3 and 4 possessed good in vitro metabolic stability. Except 3 which inhibited CYP1A2 isoform by more than 50% none of the other compounds inhibited key cytochrome P450 enzyme isoforms (CYP1A2, CYP2C9, CYP2D6 and CYP3A4) at 10 microM. Based on in vitro results one derivative 1 was tested in rodent PK and tumor studies. We found that 1 exhibited favorable pharmacokinetic characteristics of a systemically administered drug and showed better in vivo anti-tumor efficacy as compared to BA in a human colon cancer xenograft model. Our results show that BA derivatives are potential anti-cancer compounds which need to be explored in detail. PMID- 17851640 TI - Conjugative transfer of the IncP-7 carbazole degradative plasmid, pCAR1, in river water samples. AB - The transfer of the IncP-7 carbazole degradative plasmid pCAR1 from Pseudomonas putida SM1443 (derived from strain KT2440) into bacteria of river water samples was monitored using a reporter gene encoding red fluorescent protein (RFP). The number of transconjugants drastically increased in the presence of carbazole, and most appeared to belong to the genus Pseudomonas. The results suggest that the presence of carbazole benefits the appearance of transconjugants belonging to the genus Pseudomonas. Intriguingly, we also detected the transfer of pCAR1 into non Pseudomonas, Stenotrophomonas-like bacteria. PMID- 17851641 TI - Estimation of the fraction of biologically active methyl tert-butyl ether degraders in a heterogeneous biomass sample. AB - The fraction of biologically active methyl tert-butyl ether degraders in reactors is just as important for prediction of removal rates as knowledge of the kinetic parameters. The fraction of biologically active methyl tert-butyl ether degraders in a heterogeneous biomass sample, taken from a packed bed reactor, was determined using a batch kinetic based approach. The procedure involved modeling of methyl tert-butyl ether removal rates from batch experiments followed by parameter estimations. It was estimated to be 5-14% (w/w) of the measured volatile suspended solids concentration in the reactor. PMID- 17851642 TI - [Exostoses of the external auditory canal. Is the cold water hypothesis valid for patients in continental areas?]. AB - INTRODUCTION: Exostoses of the external auditory meatus are benign masses of tympanal bone that can lead to infections of the external auditory meatus in advanced cases and then need surgical treatment. Regular irritation of the auditory meatus by exposure to cold water was implicated in the causation of exostoses long ago. The present study investigates the cold water hypothesis in a patient group of continental origin. The surgical procedures and results are discussed. STUDY DESIGN: Retrospective study. MATERIALS AND METHODS: We present the epidemiological and aetiological data and postoperative findings recorded for 144 patients (167 procedures) who underwent surgical removal of exostoses from the external auditory meatus in the hospital in Wurzburg within 11 years. In attempt to glean further information about the aetiology, patients were also asked to complete a questionnaire on participation in water sports and their symptoms before and since the operation. RESULTS: Most of the patients (94%) had taken part in water sports for some years, more than 80% of them several times weekly. The most common indication for surgical removal was recurrent infection of the external ear. Although 50% of the patients reported improved hearing, no higher sound threshold was observed. Reversible complications (ear drum performation, tinnitus, opening of mastoid cells) were observed in 18% of the patients. One patient had a stenosis of the auditory canal caused by scar tissue. CONCLUSIONS: Surgical removal of exostoses in the external auditory canal is frequently fraught with controllable complications. The indications for their surgical removal should be strictly applied; the presence of exostoses in isolation is not an acceptable indication for surgery. Removal of exostoses is an adequate way of avoiding recurrent external ear infections. Improved hearing can be expected only if the self-cleaning function of the external auditory meatus is improved. PMID- 17851643 TI - Inhibitors of histone deacetylases induce tumor-selective cytotoxicity through modulating Aurora-A kinase. AB - The molecular basis of the antitumor selectivity of histone deacetylase inhibitors (HDIs) remains unclear. Centrosomal Aurora-A kinase regulates chromosomal segregation during mitosis. The overexpression or amplification of Aurora-A leads to genetic instability, and its inhibition has shown significant antitumor effects. In this paper, we report that structurally related hydroxamate LAQ824 and SK-7068 induce tumor-selective mitotic defects by depleting Aurora-A. We found that HDI-treated cancer cells, unlike nontransformed cells, exhibit defective mitotic spindles. After HDI, Aurora-A was selectively downregulated in cancer cells, whereas Aurora-B remained unchanged in both cancer and nontransformed cells. LAQ824 or SK-7068 treatment inhibited histone deacetylase (HDAC) 6 present in Aurora-A/heat shock protein (Hsp) 90 complex. Inhibition of HDAC6 acetylated Hsp90 and resulted in dissociation of acetylated Hsp90 from Aurora-A. As a result, Hsp70 binding to Aurora-A was enhanced in cancer cells, leading to proteasomal degradation of Aurora-A. Overall, these provide a novel molecular basis of tumor selectivity of HDI. LAQ824 and SK-7068 might be more effective HDIs in cancer cells with Aurora-A overexpression. PMID- 17851644 TI - The renin-angiotensin and "drinking" behavior. PMID- 17851645 TI - [Anticoagulation for stroke prevention. An update]. AB - Given the projected rising prevalence of atrial fibrillation in the near future, an increasing number of older patients will have to be treated in order to prevent stroke and systemic embolism. This article summarizes recent developments in antithrombotic treatment and risk stratification for patients with atrial fibrillation and intends to abate the still prevailing reluctance towards anticoagulation in elderly patients. PMID- 17851646 TI - [Prolonged migrainous aura and acute ischemic insult. Differential diagnosis by diffusion- and perfusion-weighted cMRI]. AB - BACKGROUND: According to the "time is brain" concept, differential diagnosis of acute stroke and prolonged migrainous aura is of vital importance in this era of systemic thrombolysis for acute cerebral ischemia. We demonstrate the value of cerebral magnetic resonance imaging (cMRI) in acute situations by presenting two patients. PATIENTS AND METHODS: Two patients were sent to our hospital for lysis treatment after the sudden appearance of global aphasia and slight right-sided hemiparesis. Further exploration was impossible due to the aphasia, and therefore we performed diffusion- and perfusion-weighted cMRI. RESULTS: We excluded acute cerebral infarction by the aid of diffusion-weighted cMRI, however left-sided cerebral hypoperfusion was seen in both patients. After resolution of neurologic symptoms, unilateral headache occurred and both patients reported pre-existing migraine with aura. CONCLUSION: Hypoperfusion of the malfunctioning brain region contralateral to the affected side of the body has been described on cMRI in only a few patients with prolonged migrainous aura. We conclude from our two cases that--provided rapid availability--cMRI can add important information for differential diagnosis, in particular when lysis therapy is a treatment option. PMID- 17851647 TI - Identification and characterization of a major QTL responsible for erect panicle trait in japonica rice (Oryza sativa L.). AB - Panicle erectness (PE) is one of the most important traits for high-yielding japonica cultivars. Although several cultivars with PE trait have been developed and released for commercial production in China, there is little information on the inheritance of PE traits in rice. In the present study, 69 widely cultivated japonica cultivars and a double haploid (DH) population derived from a cross between a PE cultivar (Wuyunjing 8) and a drooping panicle cultivar (Nongken 57) were utilized to elucidate the mechanisms of PE formation and to map PE associated genes. Our data suggested that panicle length (PL) and plant height (PH) significantly affected panicle curvature (PC), with shorter PL and PH resulting in smaller PC and consequently more erect. A putative major gene was identified on chromosome 9 by molecular markers and bulk segregant analysis in DH population. In order to finely map the major gene, all simple sequence repeats (SSR) markers on chromosome 9 as well as 100 newly developed sequence-tagged site (STS) markers were used to construct a linkage group for quantitative trait locus (QTL) mapping. A major QTL, qPE9-1, between STS marker H90 and SSR marker RM5652, was detected, and accounted for 41.72% of PC variation with pleiotropic effect on PH and PL. another QTL, qPE9-2, was also found to be adjacent to qPE9-1. In addition, we found that H90, the nearest marker to qPE9-1, used for genotyping 38 cultivars with extremely erect and drooping panicles, segregated in agreement with PC, suggesting the H90 product was possibly part of the qPE9-1 gene or closely related to it. These data demonstrated that H90 could be used for marker aided selection for the PE trait in breeding and in the cloning of qPE9-1. PMID- 17851648 TI - Relationship between glycated haemoglobin levels and mean glucose levels over time. AB - AIMS/HYPOTHESIS: HbA(1c), expressed as the percentage of adult haemoglobin that is glycated, is the most widely used measure of chronic glycaemia. Achieving near normal HbA(1c) levels has been shown to reduce long-term complications and the HbA(1c) assay is recommended to determine whether treatment is adequate and to guide adjustments. However, daily adjustments of therapy are guided by capillary glucose levels (mmol/l). We determined the relationship between an accurate measure of mean glucose levels over time and the HbA(1c) level, and whether HbA(1c) can be expressed in the same units as self-monitoring results. METHODS: Twenty-two participants with diabetes and three non-diabetic participants were included in this longitudinal observational study. Mean glucose levels were measured by continuous glucose monitoring (CGM), which measures interstitial glucose levels every 5 min, for 12 weeks. Capillary measurements were obtained four times per day to confirm the accuracy of CGM. HbA(1c) was measured at baseline and every 4 weeks. RESULTS: The HbA(1c) results at weeks 8 and 12 correlated strongly (r = 0.90) with the CGM results during the preceding 8 and 12 weeks. A curvilinear (exponential) relationship and a linear regression captured the relationship with similarly high correlations, which allowed transformation of HbA(1c) values to a calculated mean glucose level. CONCLUSIONS AND INTERPRETATION: HbA(1c) correlates closely with a complete measure of average glycaemia over the preceding 8-12 weeks. The translation of HbA(1c) to an average glucose level for reporting and management purposes is feasible. PMID- 17851649 TI - Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study. AB - AIMS/HYPOTHESIS: Raised maternal plasma total homocysteine (tHcy) concentrations predict small size at birth, which is a risk factor for type 2 diabetes mellitus. We studied the association between maternal vitamin B12, folate and tHcy status during pregnancy, and offspring adiposity and insulin resistance at 6 years. METHODS: In the Pune Maternal Nutrition Study we studied 700 consecutive eligible pregnant women in six villages. We measured maternal nutritional intake and circulating concentrations of folate, vitamin B12, tHcy and methylmalonic acid (MMA) at 18 and 28 weeks of gestation. These were correlated with offspring anthropometry, body composition (dual-energy X-ray absorptiometry scan) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-R]) at 6 years. RESULTS: Two-thirds of mothers had low vitamin B12 (<150 pmol/l), 90% had high MMA (>0.26 micromol/l) and 30% had raised tHcy concentrations (>10 micromol/l); only one had a low erythrocyte folate concentration. Although short and thin (BMI), the 6-year-old children were relatively adipose compared with the UK standards (skinfold thicknesses). Higher maternal erythrocyte folate concentrations at 28 weeks predicted higher offspring adiposity and higher HOMA-R (both p < 0.01). Low maternal vitamin B12 (18 weeks; p = 0.03) predicted higher HOMA-R in the children. The offspring of mothers with a combination of high folate and low vitamin B12 concentrations were the most insulin resistant. CONCLUSIONS/INTERPRETATION: Low maternal vitamin B12 and high folate status may contribute to the epidemic of adiposity and type 2 diabetes in India. PMID- 17851650 TI - Detection of early signals of hepatotoxicity by gene expression profiling studies with cultures of metabolically competent human hepatocytes. AB - Xenobiotic induced liver injury is a leading cause for drug withdrawal and toxicogenomics may help to identify molecular causes. Here we report studies with cultures of human hepatocytes to detect early responses of liver toxicity upon treatment with the hepatotoxin Aroclor 1254. We studied transcript abundance of 302 genes with biological functions in detoxification, cell proliferation, tumor development, stress response, signal transduction, apoptosis and cell cycle regulation. More than 40 genes were regulated by at least twofold change, the majority coding for xenobiotic defense. In the case of CYP monooxygenases induction of coded protein was confirmed by Western immunoblotting whereas catalytic activities were determined by assaying for testosterone hydroxylase activity. There was good agreement between gene and protein expression and enzyme activity of CYP monooxygenases. In conclusion, xenobiotic induced hepatotoxicity may arise via several mechanisms and gene expression profiling helps to pinpoint location and pathways perturbed by drugs and chemicals. PMID- 17851651 TI - Determination of impurities in magnesium niobate by slurry introduction axially viewed inductively coupled plasma optical emission spectrometry. AB - A simple preparation scheme is described for the quantitative analysis of a magnesium niobate sample using slurry introduction axially viewed inductively coupled plasma optical emission spectrometry. Relationships between the stability of slurries and the conditions, such as particle size, pH, dispersant and amount of dispersant, were investigated experimentally. The MgNb(2)O(6) slurry sample was prepared by adding the dispersant sodium polyacrylate and agitation in an ultrasonic bath to ensure good dispersion. Under optimization of pH and amount of dispersant, an analysis of minor and trace impurities (Ba, Ca, Cr, Cu, Fe, Mn, Ni, Pb) in magnesium niobate was accomplished. Applying a paired t test, we showed that the results were in agreement at a 95% confidence level with the reference values obtained by a fusion method for a magnesium niobate sample, which verified that the calibration curves could be established by aqueous standards. Analytical results demonstrate that the factors that affected the accuracy of determination for MgNb(2)O(6) are mainly the particle size of the sample and the stability of slurry. PMID- 17851653 TI - Prediction of retention times of polycyclic aromatic hydrocarbons and n-alkanes in temperature-programmed gas chromatography. AB - We have developed an iterative procedure for predicting the retention times of polycyclic aromatic hydrocarbons (PAHs) and n-alkanes during separations by temperature-programmed gas chromatography. The procedure is based on estimates of two thermodynamic properties for each analyte (the differences in enthalpy and entropy associated with movements between the stationary and mobile phases) derived from data acquired experimentally in separations under isothermal conditions at temperatures spanning the range covered by the temperature programs in ten-degree increments. The columns used for this purpose were capillary columns containing polydimethylsiloxane-based stationary phases with three degrees of phenyl substitution (0%, 5%, and 50%). Predicted values were mostly within 1% of experimentally determined values, implying that the method is stable and precise. PMID- 17851654 TI - A DNA electrochemical sensor prepared by electrodepositing zirconia on composite films of single-walled carbon nanotubes and poly(2,6-pyridinedicarboxylic acid), and its application to detection of the PAT gene fragment. AB - Carboxyl group-functionalized single-walled carbon nanotubes (SWNTs) and 2,6 pyridinedicarboxylic acid (PDC) were electropolymerized by cyclic voltammetry on a glassy-carbon electrode (GCE) surface to form composite films (SWNTs/PDC). Zirconia was then electrodeposited on the SWNTs/PDC/GCE from an aqueous electrolyte containing ZrOCl2 and KCl by cycling the potential between -1.1 V and +0.7 V at a scan rate of 20 mV s(-1). DNA probes with a phosphate group at the 5' end were easily immobilized on the zirconia thin films, because of the strong affinity between zirconia and phosphate groups. The sensors were characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). EIS was used for label-free detection of the target DNA by measuring the increase of the electron transfer resistance (R(et)) of the electrode surface after the hybridization of the probe DNA with the target DNA. The PAT gene fragment and polymerase chain reaction (PCR) amplification of the NOS gene from transgenically modified beans were satisfactorily detected by use of this DNA electrochemical sensor. The dynamic range of detection of the sensor for the PAT gene fragment was from 1.0 x 10(-11) to 1.0 x 10(-6) mol L(-1) and the detection limit was 1.38 x 10(-12) mol L(-1). PMID- 17851655 TI - Vesicular release of glutamate from hippocampal neurons in culture: an immunocytochemical assay. AB - Glutamate, the main excitatory neurotransmitter in the brain, may cause excitotoxic damage through excessive release during a number of pathological conditions. We have developed an immunocytochemical assay to investigate the mechanisms and regulation of glutamate release from intact, cultured neurons. Our results indicate that cultured hippocampal neurons have a large surplus of glutamate available for release upon chemically induced depolarization. Long incubations with high K(+)-concentrations, and induction of repetitive action potentials with the K(+)-channel blocker 4-aminopyridine (4-AP), caused a significant reduction in glutamate labeling in a subset of boutons, demonstrating that transmitter release exceeded the capacity for replenishment. The number of boutons where release exceeded replenishment increased continuously with time of stimulation. This depletion was Ca(2+)-dependent and sensitive to bafilomycin A1 (baf), indicating that it was dominated by vesicular release mechanisms. The depletion of glutamate from cell bodies and dendrites was also Ca(2+)-dependent. Thus, under the present conditions, cytosolic glutamate is taken up in vesicles prior to release, and the main escape route for the amino acid is through vesicular exocytosis. Depolarization with lower concentrations of K(+) caused sustainable release of glutamate, i.e., without full depletion. PMID- 17851656 TI - Tone-sequence analysis in the auditory cortex of awake macaque monkeys. AB - The present study analyzed neuronal responses to two-tone sequences in the auditory cortex of three awake macaque monkeys. The monkeys were passively exposed to 430 different two-tone sequences, in which the frequency of the first tone and the interval between the first and the second tone in the sequence were systematically varied. The frequency of the second tone remained constant and was matched to the single-tone frequency sensitivity of the neurons. Multiunit activity was recorded from 109 sites in the primary auditory cortex and posterior auditory belt. We found that the first tone in the sequence could inhibit or facilitate the response to the second tone. Type and magnitude of poststimulatory effects depended on the sequence parameters and were related to the single-tone frequency sensitivity of neurons, similar to previous observations in the auditory cortex of anesthetized animals. This suggests that some anesthetics produce, at the most, moderate changes of poststimulatory inhibition and facilitation in the auditory cortex. Hence many properties of the sequence sensitivity of neurons in the auditory cortex measured in anesthetized preparations can be applied to neurons in the auditory cortex of awake subjects. PMID- 17851657 TI - Ectopic cervical thymic tissue: can imaging obviate biopsy and surgical removal? AB - Thymic tissue rests can be found all along the route of thymic descent from the neck into the anterior mediastinum and are frequently misinterpreted as pathological masses, which leads to biopsy or surgical removal. We present a case of ectopic thymic tissue in the neck and review the imaging characteristics of our patient and those found in the literature to determine if biopsy for this normal variation can be avoided. US findings of ectopic tissue reveal the exact tissue characteristics of normal thymus. The ectopic thymus may have an angulated configuration and mold over adjacent structures rather than displacing or invading them. If further verification is needed, T1-weighted MR images show homogeneous isointense or slightly hyperintense tissue compared with muscle and T2-weighted images show hyperintensity. The mass has the same structure as the normal thymus. We believe, on the basis of these findings, that one can confidently avoid the need for biopsy to prove that the discovered mass is ectopic thymus tissue. PMID- 17851658 TI - Spider silk softening by water uptake: an AFM study. AB - We have investigated the mechanical properties of spider dragline fibers of three Nephila species under varied relative humidity. Force maps have been collected by atomic force microscopy. The Young's modulus E was derived from the indentation curves of each pixel by the modified Hertz model. An average decrease in E by an order of magnitude was observed upon immersion of the fiber in water. Single fiber stretching experiments were carried out for comparison, and also showed a strong dependence on relative humidity. However, the absolute values of E are significantly higher than those obtained by indentation. The results of this work thus show that the elastic properties of spider silk are highly anisotropic, and that the silk softens significantly for both tensile and compressional strain (indentation) upon water uptake. In addition, the force maps indicate a surface structure on the sub-micron scale. PMID- 17851659 TI - Transcriptional profile induced by furazolidone treatment of Shigella flexneri. AB - Shigella flexneri is a facultative intracellular pathogen responsible for endemic shigellosis especially in developing countries. Furazolidone, a nitrofuran derivative, is very effective against the infection with S. flexneri. To examine potential effects of furazolidone on this germ, a whole-genome DNA microarray was constructed and transcriptional profiles of the responses to furazolidone were determined. The expressing data revealed adaptive responses of S. flexneri to oxidative stress induced by furazolidone treatment. Iron metabolism was found to be disturbed by furazolidone through derepression of the iron uptake regulon. In addition, energy metabolism, amino acid metabolism, cofactors metabolism, and DNA repair system were also affected by the drug. These data establish a potential for furazolidone to enhance free radical reactions through reductive activation by oxygen-sensitive nitroreductase. Moreover, we provide evidence that furazolidone is able to cause metabolic dysfunction, which cannot always be attributed to oxidative stress, and interactions between reductive metabolites of furazolidone and S. flexneri should be considered. PMID- 17851661 TI - Density-dependent dispersal in integrodifference equations. AB - Many species exhibit dispersal processes with positive density- dependence. We model this behavior using an integrodifference equation where the individual dispersal probability is a monotone increasing function of local density. We investigate how this dispersal probability affects the spreading speed of a single population and its ability to persist in fragmented habitats. We demonstrate that density-dependent dispersal probability can act as a mechanism for coexistence of otherwise non-coexisting competitors. We show that in time varying habitats, an intermediate dispersal probability will evolve. Analytically, we find that the spreading speed for the integrodifference equation with density-dependent dispersal probability is not linearly determined. Furthermore, the next-generation operator is not compact and, in general, neither order-preserving nor monotonicity-preserving. We give two explicit examples of non-monotone, discontinuous traveling-wave profiles. PMID- 17851662 TI - [Hypopigmented melanocytic tumors with spindle cells. A review]. AB - Hypopigmented and achromatic melanocytic tumors with spindle cells represent a diagnostic challenge. Spindle cell nevi resemble neural tumors. Desmoplastic nevi imitate dermatofibromas. Hypopigmented and amelanotic blue nevi are variants of the common and cell-rich blue nevus with an enhanced difficulty to make a correct diagnosis due to the lack of pigment. All of the above benign melanocytic tumors with proliferations of hypopigmented spindle cells can more or less show aspects of desmoplastic melanoma. The differential diagnosis of these entities demands a combination of clinical and histological parameters as well as supporting immunostaining. Regarding desmoplastic melanoma, diagnoses frequently made are benign spindle cell neoplasms, scar or unspecific inflammatory condition. As the histological aspects can be so misleading, attention is necessary in order to make the correct diagnosis. Particular care must be taken to rule out desmoplastic melanoma in the case of spindle cell proliferations, a cicatricial or inflammatory process in the classical settings of face, volar skin, or mucous membranes. The spindle cell melanoma must be distinguished from other types of malignant spindle cell neoplasms, which can involve the skin. The differential diagnosis with such tumors is entrusted mainly to immunostaining. PMID- 17851660 TI - Immunopathogenesis of IgAN. AB - The defining hallmark of IgA nephropathy (IgAN) is deposition of polymeric IgA1 in the glomerular mesangium accompanied by a mesangial proliferative glomerulonephritis. The mechanisms involved in mesangial polymeric IgA1 deposition and the initiation of inflammatory glomerular injury remain unclear. This lack of a complete understanding of the pathogenesis of IgAN has meant that there is still no treatment known to modify mesangial deposition of IgA. Increasing evidence, however, supports the importance of IgA-containing immune complex formation as a pivotal factor driving mesangial IgA deposition and triggering of glomerular injury. A number of potentially important changes to the IgA1 molecule have been identified in IgAN, which may contribute to immune complex formation. These changes suggest that the polymeric IgA1 that deposits in IgA nephropathy is derived from mucosally primed plasma cells. The presence of this IgA in the circulation reflects displacement of mucosal B lineage cells to systemic sites and may be the result of mishoming of lymphocytes trafficking along the mucosa-bone marrow axis. PMID- 17851663 TI - Embryogenesis and plant regeneration of hot pepper (Capsicum annuum L.) through isolated microspore culture. AB - We report high frequencies of embryo production and plant regeneration through isolated microspore culture of hot pepper (Capsicum annuum L.). Microspores cultured in modified NLN medium (NLNS) divided and developed to embryos. Globular and heart-shaped embryos were observed from 3 weeks after the beginning of culture, and many embryos reached the cotyledonary stage after 4 weeks of culture. These cotyledonary embryos developed to plantlets after transfer to solid B5 basal medium. We also optimized conditions for embryo production by varying the pretreatment media, the carbon sources, and culture densities. Heat shock treatment in sucrose-starvation medium was more effective than in B5 medium. Direct comparisons of sucrose and maltose as carbon sources clearly demonstrated the superiority of sucrose compared to maltose, with the highest frequency of embryo production being obtained in 9% (w/v) sucrose. Microspore plating density was critical for efficient embryonic induction and development, with an optimal plating density of 8 x 10(4)-10 x 10(4)/ml. Under our optimized culture conditions, we obtained over 54 embryos, and an average of 5.5 cotyledonary embryos when 10 x 10(4) microspores were grown on an individual plate. PMID- 17851664 TI - Value of contrast-enhanced ultrasonography for detecting renal infarcts proven by contrast enhanced CT. A feasibility study. AB - The effectiveness of contrast-enhanced ultrasonography (CEUS) in the evaluation of patients with acute renal infarcts was investigated, using contrast-enhanced helical computed tomography (CT) as the reference imaging procedure. Twenty-seven consecutive patients with acute renal infarcts detected with contrast-enhanced helical CT underwent CEUS. Digital cine-clips of CEUS were evaluated by two independent readers blinded to CT findings. Image quality was rated subjectively on a four-point scale. Then, readers were asked to assign a confidence level in diagnosis of renal infarct at the upper pole, medium portion, and lower pole of each kidney according to a five-degree scale, ranging from definitely absent to definitely present. ROC curve analysis was employed to assess the overall confidence of diagnosis of infarct, and weighted kappa values were calculated to assess inter-reader agreement. The subjective image quality of CEUS was lower than the image quality of CT at the upper poles. However, the diagnostic performance of CEUS was excellent (area under receiver-operator characteristic curve 0.992 +/- 0.006 for reader 1; 0.991 +/- 0.007 for reader 2), with very good inter-reader agreement (weighted kappa value = 0.83). CEUS is a reproducible tool to detect acute renal infarcts in men, with a diagnostic performance approaching that of CT. PMID- 17851665 TI - High-resolution myocardial stress perfusion at 3 T in patients with suspected coronary artery disease. AB - To implement a high-resolution first-pass myocardial perfusion imaging protocol (HRPI) at 3 T, and to evaluate the feasibility, image quality and accuracy of this approach prospectively in patients with suspected CAD. We hypothesized that utilizing the gain in SNR at 3 T to increase spatial resolution would reduce partial volume effects and subendocardial dark rim artifacts in comparison to 1.5 T. HRPI studies were performed on 60 patients using a segmented k-space gradient echo sequence (in plane resolution 1.97 x 1.94 mm(2)). Semiquantitative assessment of dark rim artifacts was performed for the stress studies on a slice by-slice basis. Qualitative visual analysis was compared to quantitative coronary angiography (QCA) results; hemodynamically significant CAD was defined as stenosis >or=70% at QCA. Dark rim artifacts appeared in 108 of 180 slices (average extent 1.3 +/- 1.2 mm representing 11.8 +/- 10.8% of the transmural myocardial thickness). Sensitivity, specifity, and test accuracy for the detection of significant CAD were 89%,79%, and 85%. HRPI studies at 3 T are feasible in a clinical setting, providing good image quality and high accuracy for detection of significant CAD. The presence of dark rim artifacts does not appear to represent a diagnostic problem when using a HRPI approach. PMID- 17851666 TI - Dual-source computed tomography in patients with acute chest pain: feasibility and image quality. AB - The aim of this study was to determine the feasibility and image quality of dual source computed tomography angiography (DSCTA) in patients with acute chest pain for the assessment of the lung, thoracic aorta, and for pulmonary and coronary arteries. Sixty consecutive patients (32 female, 28 male, mean age 58.1+/-16.3 years) with acute chest pain underwent contrast-enhanced electrocardiography gated DSCTA without prior beta-blocker administration. Vessel attenuation of different thoracic vascular territories was measured, and image quality was semi quantitatively analyzed by two independent readers. Image quality of the thoracic aorta was diagnostic in all 60 patients, image quality of pulmonary arteries was diagnostic in 59, and image quality of coronary arteries was diagnostic in 58 patients. Pairwise intraindividual comparisons of attenuation values were small and ranged between 1+/-6 HU comparing right and left coronary artery and 56+/-9 HU comparing the pulmonary trunk and left ventricle. Mean attenuation was 291+/ 65 HU in the ascending aorta, 334+/-93 HU in the pulmonary trunk, and 285+/-66 HU and 268+/-67 HU in the right and left coronary artery, respectively. DSCTA is feasible and provides diagnostic image quality of the thoracic aorta, pulmonary and coronary arteries in patients with acute chest pain. PMID- 17851667 TI - Ontogeny of flight initiation in the fly Drosophila melanogaster: implications for the giant fibre system. AB - There are two modes of flight initiation in Drosophila melanogaster-escape and voluntary. Although the circuitry underlying escape is accounted for by the Giant fibre (GF) system, the system underlying voluntary flight initiation is unknown. The GF system is functionally complete before the adult fly ecloses, but immature adults initially fail to react to a stimulus known to reliably evoke escape in mature adults. This suggests that escape in early adulthood, approximately 2-h post-eclosion, is not automatically triggered by the hard-wired GF system. Indeed, we reveal that escape behaviour displays a staged emergence during the first hour post-eclosion, suggesting that the GF system is subject to declining levels of suppression. Voluntary flight initiations are not observed at all during the period when the GF system is released from its suppression, nor indeed for some time after. We addressed the question whether voluntary flight initiation requires the GF system by observing take-off in Shak-B ( 2 ) mutant flies, in which the GF system is defunct. While the escape response is severely impaired in these mutants, they displayed normal voluntary flight initiation. Thus, the escape mechanism is subject to developmental modulation following eclosion and the GF system does not underlie voluntary flight. PMID- 17851668 TI - The prevalence of colorectal neoplasia in patients with end-stage renal disease: a case-control study. AB - BACKGROUND AND PURPOSE: The scarcity of organs for transplantation has led to aggressive pretransplant evaluations. Many younger kidney transplant patients with end-stage renal disease, who would be ordinarily at average risk for colorectal cancer, undergo screening colonoscopy as part of this evaluation. The purpose of this study was to determine the prevalence of colorectal neoplasia in patients with end-stage renal disease who are potential transplant candidates. MATERIALS AND METHODS: We performed a retrospective chart review analysis on 57 kidney transplant candidates who underwent pretransplant screening colonoscopy between August 1999 and December 2004. The control group was comprised of 60 age- and gender-matched subjects without end-stage renal disease who underwent routine screening colonoscopy. RESULTS: The prevalence of polyps in end-stage renal disease patients was 37 vs 22% in the control group (p=0.07, not significant). None of the risk factors studied were found to predict the presence of polyps in the study group. CONCLUSION: These results suggest that screening guidelines for colorectal cancer for the general population should be adequate for potential kidney transplant recipients. PMID- 17851669 TI - [Expert assessment in cases of osteoporosis]. AB - There are about 8 million people in German-speaking countries who suffer from osteoporosis, making it the most common bone disease. Osteoporotic fractures can significantly impair quality of life and working ability in those affected, and they also give rise to huge expenditures in the healthcare system. Expert assessments should be based on estimated risk of fracture, risk of falling, pain, fitness for work, degree of disability, need for rehabilitation, and causality. PMID- 17851670 TI - [Medico-legal assessment of systemic sclerosis]. AB - Diagnosis and management of the rare disease systemic sclerosis (scleroderma) is a challenge for the physician, not least due to the possible multitude of organ systems involved. The medico-legal assessment is important for the patient claiming insurance benefits or applying for early retirement due to scleroderma. Both the specialist for sclerosis and the impartial medico-legal assessor have to cooperate and understand the respective partner's requirements and terminology. Evaluations of individual organ impairments, handicaps and disabilities have to be taken into account when assessing the degree of impairment of occupational activity. PMID- 17851671 TI - [Current status of ambulatory rheumatologic health care in Germany. Structure of health care and range of services]. AB - AIM: To gather information on current organizational structures in rheumatologic ambulatory health care in Germany. Based on the results recommendations on future structures will be discussed. METHODS: This study involved data collection and statistical analysis via a structured 10-page questionnaire among the members of the German Association of Rheumatologists. The questions concerned a variety of topics including information on office structures, patient structure, structure of services offered, co-operation with colleagues and hospitals, quality assurance measures, economic factors, and a subjective assessment of the health care structures in rheumatology by the participants. RESULTS: Data obtained from 197 rheumatologists who participate in health care were analyzed. In this paper results concerning the organizational as well as the medical ambulatory health care structure will be presented. Data on economic factors will be presented in part 2 of this study. CONCLUSIONS: The organization of ambulatory treatment regarding processes and treatment differences between office-based physicians and rheumatologic outpatient departments in hospitals was very homogeneous. However, physicians in the eastern regions treated significantly more patients compared with the western parts of Germany. This difference was also observed between the north and south. Differences in patient groups (e.g. underlying diseases) were reported between different sub-groups of rheumatologists (e.g. internal specialists vs. GP vs. orthopedic rheumatologists). Integrated health care, as promoted by German social law, did not play a major role. Overall there was a high level of self-initiated training of physicians and participation in education of patients and other physicians. PMID- 17851672 TI - Obstetric outcomes in nulliparous women aged 35 and over with singleton pregnancies conceived by in vitro fertilization. AB - OBJECTIVE: To investigate obstetric outcomes in singleton pregnancies conceived by in vitro fertilization (IVF) to nulliparous women older than 35 compared to those of their younger counterparts. METHODS: Nulliparous women 35 years and older at delivery conceived by IVF (n = 89) were compared with nulliparous women 34 years and younger at delivery conceived by IVF (n = 48). Data included antenatal data, gestational age at delivery, maternal and neonatal complications and mode of delivery. RESULTS: The incidence of pregnancy-induced hypertension in the younger group was significantly higher than that in the elderly group (13 vs. 3.4%, P = 0.043). There were no measurable differences in other obstetric outcomes such as placental abnormality, premature delivery or neonatal asphyxia between the two groups. CONCLUSION: The current results suggest that obstetric complications in pregnancies conceived IVF are attributed to mechanisms other than those depend on advanced maternal age. PMID- 17851673 TI - Pregnancy rates after hysteroscopic polypectomy depending on the size or number of the polyps. AB - OBJECTIVE: To assess the reproductive benefits of hysteroscopic polypectomy in previous infertile women depending on the size or number of the polyps. DESIGN AND METHODS: In this retrospective study, from February 2000 to September 2005, totally 83 selected women were included with: a) diagnoses of primary or secondary infertility, endometrial polyp/polyps and abnormal uterine bleeding. Endometrial polyps were diagnosed by transvaginal ultrasound followed by diagnostic hysteroscopy, to confirm diagnosis, and hysteroscopic polypectomy. All 83 subjects who consisted the study group, met inclusion criteria: age under 35 years, at least 12 months of infertility, from 3 to 8 months menstrual disorders (intermenstrual bleeding or spotting, menometrorrhagia or menorrhagia) and from 3 to 18 months of follow-up with attempts to conceive after hysteroscopic polypectomy. The endometrial polyp/polyps appeared to be the only reason to explain their infertility after infertility workup of the couples. There was a comparison of fertility rates after hysteroscopic polypectomy between patients having endometrial polyp < or = 1 cm and patients with bigger or multiple polyps. RESULTS: Of the 83 subjects, all were found to have endometrial polyps in diagnostic hysteroscopy, confirmed at histologic examination after hysteroscopic polypectomy. Among patients of the study group, there were no significant differences in age, type or length of infertility, or follow-up period after the procedure. The mean size of the endometrial polyps was 1.9 +/- 1.4.cm. Thirty-one patients had endometrial polyp < or = 1 cm and 52 patients had bigger or multiple endometrial polyps. Following polypectomy, menstrual pattern was normalized in 91.6% of patients. Spontaneous pregnancy and delivery at term rates, in the total population of the study, increased after the procedure and were 61.4% and 54.2% respectively. There was no statistical difference in fertility rates between patients having polyps < or = 1 cm and patients having >1 cm polyps or multiple polyps. Spontaneous abortion rate in the first trimester of pregnancy was 6% of the total number of patients and there was no statistical difference between patients with small or bigger/multiple polyps. Type of infertility did not affect fertility rates after hysteroscopic polypectomy. Complication rate after hysteroscopic polypectomy was as low as 2.4%, while recurrence rate of the procedure reached 4.9% of patients. CONCLUSION: Hysteroscopic polypectomy of endometrial polyps appeared to improve fertility and increase pregnancy rates in previous infertile women with no other reason to explain their infertility, irrespective of the size or number of the polyps. Type of infertility of patients seems not to affect fertility rates after hysteroscopic polypectomy. Menstrual pattern was normalized in the majority of patients after hysteroscopic polypectomy. In addition, hysteroscopic polypectomy is a safe procedure with low complication rate. PMID- 17851674 TI - Complete surgical resection of retroperitoneal leiomyosarcoma in pregnancy: a case report. AB - Retroperitoneal soft tissue sarcoma (RPS) is extremely rare in pregnancy, so there has been little experience in dialing with this condition. We report our experience of a pregnant patient with a retroperitoneal soft tissue sarcoma, which was treated by complete surgical resection at 17 weeks gestation. After regular follow-up, the patient admitted to our hospital in labor, in the 38th gestational week and vaginally delivered a male fetus weighing 3,200 g with Apgar score of 8 and 10 at 1 and 5 min respectively. Adjuvant radiotherapy and chemotherapy is controversial in RPS and due to postoperative continuation of pregnancy in our case, the adjuvant therapy was not practiced. The patient had an uneventful recovery, and no recurrence was detected for 20 months in the follow up period. PMID- 17851675 TI - The evaluation of the tensor veli palatini muscle function with electromyography in chronic middle ear diseases. AB - Although there are several factors affecting the pathogenesis of chronic otitis, the pathological process has not been entirely defined yet. One of the theories suggested for the development of middle ear diseases is tubal dysfunction. The aim of the study is to analyze the function of the tensor veli palatini (TVP) muscle electromyographically in chronic middle ear pathologies and to evaluate the role of this muscle in eustachian tube dysfunction and pathogenesis of associated middle ear diseases by comparing with the results of healthy individuals. STUDY DESIGN: A prospective, controlled, clinical trial. We enrolled 24 patients with chronic middle ear pathologies into our study and 18 controls without any previous ear problem. Electromyographic (EMG) needle was inserted into the TVP muscles in all patients transnasally. Functions of the TVP muscle were analyzed by using the amplitudes of the motor unit potential (MUP) and MUP durations detected on EMG. MUP amplitudes and MUP durations were compared statistically in all groups. When the mean MUP amplitudes and durations obtained from TVP muscles of all ears from the patient group were compared to the mean MUP amplitudes and durations obtained from healthy individuals, no statistically significant difference was observed between sick ears and control ears. Values obtained from the sick ears needed to be compared with mean values obtained from the control group separately, since absence of statistically significant difference cannot mean that we should ignore individual muscle dysfunction. The results we obtained from our study support that in the formation of different middle ear pathologies, myogenic defects in the eustachian tube have limited effects, except for existence of a predisposing factor like palate pathology. In all patients with chronic middle ear disease it is not appropriate to expect functional muscle dysfunction, however evaluation of TVP muscle function correctly may be helpful for bringing up the underlying possible muscle and nerve pathologies not in all patients. PMID- 17851676 TI - Dental superimposition: a pilot study for standardising the method. AB - Dental superimposition is becoming more and more important because of the increasing number of illegal immigrants (at least in Italy), with no clinical history, no personal effects or relatives useful for genetic comparison, whose friends and acquaintances can usually only produce photographs. Very few authors have been involved in devising and using this method. The goal of the present study is to establish whether it is possible, and under which conditions, to identify individuals by dental superimposition of teeth visible in an ante-mortem photograph and dental casts of an unidentified body, and to develop a protocol for the spatial orientation analysis of the dentition and qualitative and semi quantitative analysis of superimpositions. A non-mathematical scoring system has been applied to each superimposition as a first step towards the optimisation of a cheap, quick, semi-quantitative method of identifying individuals when other more used methods are not applicable. PMID- 17851677 TI - Differential expression of the keratan sulphate proteoglycan, keratocan, during chick corneal embryogenesis. AB - Keratan sulphate (KS) proteoglycans (PGs) are key molecules in the connective tissue matrix of the cornea of the eye, where they are believed to have functional roles in tissue organisation and transparency. Keratocan, is one of the three KS PGs expressed in cornea, and is the only one that is primarily cornea-specific. Work with the developing chick has shown that mRNA for keratocan is present in early corneal embryogenesis, but there is no evidence of protein synthesis and matrix deposition. Here, we investigate the tissue distribution of keratocan in the developing chick cornea as it becomes compacted and transparent in the later stages of development. Indirect immunofluorescence using a new monoclonal antibody (KER-1) which recognises a protein epitope on the keratocan core protein demonstrated that keratocan was present at all stages investigated (E10-E18), with distinct differences in localisation and organisation observed between early and later stages. Until E13, keratocan appeared both cell associated and in the stromal extracellular matrix, and was particularly concentrated in superficial tissue regions. By E14 when the cornea begins to become transparent, keratocan was located in elongate arrays, presumably associated along collagen fibrils in the stroma. This fibrillar label was still concentrated in the anterior stroma, and persisted through E15-E18. Presumptive Bowman's layer was evident as an unlabelled subepithelial zone at all stages. Thus, in embryonic chick cornea, keratocan, in common with sulphated KS chains in the E12-E14 developmental period, exhibits a preferential distribution in the anterior stroma. It undergoes a striking reorganisation of structure and distribution consistent with a role in relation to stromal compaction and corneal transparency. PMID- 17851678 TI - Mutational analysis of ErbB2 intracellular localization. AB - In the present study, the sub-cellular localization of ErbB2 and its mutants expressed as GFP-tagged proteins in MCF-7 cells or endogenous ErbB2 in SKBR3 cells was examined. The data presented here demonstrate that the full-length ErbB2 was localized at the cytoplasmic membrane and ErbB2 ICD localized in the nucleus predominantly. The sequence of ErbB2 ICD contains the information supporting its nuclear translocation and cytoplasmic retention. A region (residues 721-970) harboring an arginine triplet is essential for the cytoplasmic trafficking of ErbB2. The results indicate that differential sub-cellular localization of ErbB2 ICD and the full-length ErbB2 is dependent on their structural determinants. The present results give initial clues for further analysis of the mechanism of ErbB2 intracellular localization. PMID- 17851679 TI - Hyperplastic polyps and sessile serrated 'adenomas' of the colon and rectum display gastric pyloric differentiation. AB - The serrated polyp-neoplasia pathway is a novel concept that has been demonstrated to differ from the conventional adenoma-carcinoma pathway. To characterize the phenotypic patterns of differentiation in colorectal serrated polyps, we examined the immunohistochemical expression profile of gastric (MUC5AC, TFF1, MUC6, GlcNAcalpha1 --> 4Gal --> R, and PDX1) and intestinal (MUC2, TFF3, and CDX2) epithelial markers in 15 hyperplastic polyps (HPs), 29 sessile serrated adenomas (SSAs),12 traditional serrated adenomas (TSAs), and 16 conventional adenomas (CAs). MUC5AC and TFF1 were upregulated in the HPs, SSAs, and TSAs. MUC6 was expressed in the HPs and SSAs. GlcNAcalpha1 --> 4Gal --> R was expressed only in the SSAs. Although MUC2 expression was preserved, TFF3 was downregulated in the HPs, SSAs, and TSAs. PDX1 was upregulated in the HPs, SSAs, and TSAs. On the other hand, CDX2 was downregulated in the HPs and SSAs. The colorectal serrated polyps showed higher expression of gastric makers than CAs. The HPs and SSAs showed gastric and intestinal mixed phenotype expression with gastric pyloric organoid differentiation and almost identical, but different from the TSAs, marker profile. PDX1 up-regulation and CDX2 down-regulation could be important for the induction of a gastric pyloric pattern of cell differentiation in colorectal serrated polyps. PMID- 17851680 TI - Kinetics of creatine ingested as a food ingredient. AB - The aim of the present study was to test if the consumption of creatine incorporated in food bars modifies creatine plasma kinetics, erythrocyte retention and loss in urine and in feces when compared with its consumption in the form of an aqueous solution (AS). Seventeen healthy young men ingested 2 g creatine either in the form of AS, or incorporated in a protein (PP)- or in a beta-glucan (BG)-rich food bar. Kinetics of plasma creatine was measured for 8-h duration and urinary excretion for 24 h. Then, the subjects received the same treatment thrice a day for 1 week at the end of which creatine contents were determined in erythrocytes and in feces (n = 4 for feces). The three crossover treatments were interspaced by a 40 +/- 1.2-day wash-out. Absorption of creatine was slowed down by 8-fold in the presence of BG (P < 0.001) and by 4-fold with PP (P < 0.001) whereas the velocity rate constant of elimination and the area under the curve were not modified. Urinary loss of creatine in the first 24 h following ingestion was 15 +/- 1.9% in AS and 14 +/- 2.2% in PP conditions (NS), whereas it was only 8 +/- 1.2% with BG (P = 0.004). Increase in creatine concentration in erythrocyte was similar in whatever form the creatine was ingested. Creatine seems to be totally absorbed since no creatine or creatinine was detectable in feces. No side effects were reported. In conclusion, ingestion of creatine combined with BG facilitates its retention by slowing down its absorption rate and reducing its urinary excretion. PMID- 17851681 TI - Effect of caffeine ingestion on one-repetition maximum muscular strength. AB - Multiple studies corroborate the ergogenic properties of caffeine (CAF) for endurance performance, yet fewer investigations document the efficacy of acute caffeine intake for intense, short-term exercise. The aim of the study was to determine the ergogenic potential of caffeine during testing of muscular strength and endurance. Twenty-two resistance-trained men ingested CAF (6 mg/kg) or placebo (PL) 1 h pre-exercise in a randomized, double-blind crossover design. They refrained from caffeine intake and strenuous exercise 48 and 24 h, respectively, pre-visit. Initially, resting heart rate and blood pressure were obtained followed by one-repetition maximum (1-RM) testing on the barbell bench press and leg press. Upon determination of 1-RM, participants completed repetitions to failure at 60%1-RM. Heart rate, blood pressure, and rating of perceived exertion (RPE) were measured after the final repetition. Compared to PL, there was no effect (P > 0.05) of caffeine on muscular strength, as 1-RM bench press (116.4 +/- 23.6 kg vs. 114.9 +/- 22.8 kg) and leg press (410.6 +/- 92.4 kg vs. 394.8 +/- 95.4 kg) were similar. Total weight lifted during the 60% 1 RM trial was 11 and 12% higher for the bench press and leg press with caffeine compared to placebo, yet did not reach significance. RPE was similar at the end of resistance exercise with CAF vs. PL. Acute caffeine intake does not significantly alter muscular strength or endurance during intense bench press or leg press exercise, yet the practical importance of the increased muscular endurance remains to be explored. PMID- 17851682 TI - Influence of exercise intensity on time spent at high percentage of maximal oxygen uptake during an intermittent session in young endurance-trained athletes. AB - The purpose of this study was to compare, during a 30s intermittent exercise (IE), the effects of exercise intensity on time spent above 90% VO2max(t90VO2max) and time spent above 95% VO2max(t95VO2max) in young endurance trained athletes. We hypothesized that during a 30sIE, an increase in exercise intensity would allow an increase in t90VO2max and t95VO2max due to a decrease in time to achieve 90% or 95% of VO2max. Nine endurance-trained male adolescents took part in three field tests. After determination of their VO2max and maximal aerobic velocity (MAV), they performed, until exhaustion, two intermittent exercise sessions alternating 30s at 100% of MAV (IE(100)) or 110% of MAV (IE(110)) and 30s at 50% of MAV. Mean time to exhaustion (t (lim)) values obtained during IE(100) were significantly longer than during IE(110) (p < 0.01). Moreover, no significant difference was found in t90VO2max or t95VO2max) expressed in absolute or relative (%t (lim)) values between IE(100) and IE(110). In conclusion, an increased of 10% of exercise intensity during a 30s intermittent exercise model (with active recovery), does not seem to be the most efficient exercise to solicit oxygen uptake to its highest level in young endurance-trained athletes. PMID- 17851683 TI - Locus coeruleus noradrenergic neurons and CO2 drive to breathing. AB - The Locus coeruleus (LC) has been suggested as a CO(2) chemoreceptor site in mammals. In the present study, we assessed the role of LC noradrenergic neurons in the cardiorespiratory and thermal responses to hypercapnia. To selectively destroy LC noradrenergic neurons, we administered 6-hydroxydopamine (6-OHDA) bilaterally into the LC of male Wistar rats. Control animals had vehicle (ascorbic acid) injected (sham group) into the LC. Pulmonary ventilation (plethysmograph), mean arterial pressure (MAP), heart rate (HR), and body core temperature (T (c), data loggers) were measured followed by 60 min of hypercapnic exposure (7% CO(2) in air). To verify the correct placement and effectiveness of the chemical lesions, tyrosine hydroxylase immunoreactivity was performed. Hypercapnia caused an increase in pulmonary ventilation in all groups, which resulted from increases in respiratory frequency and tidal volume (V (T)) in sham operated and 6-OHDA-lesioned groups. The hypercapnic ventilatory response was significantly decreased in 6-OHDA-lesioned rats compared with sham group. This difference was due to a decreased V (T) in 6-OHDA rats. LC chemical lesion or hypercapnia did not affect MAP, HR, and T (c). Thus, we conclude that LC noradrenergic neurons modulate hypercapnic ventilatory response but play no role in cardiovascular and thermal regulation under resting conditions. PMID- 17851684 TI - Absence of hardly pursued updating in a running memory task. AB - In a running memory span task, the participants are presented with a list of items (e.g. numbers or words) of an unknown length, because this length varies from trial to trial. In one variation of the procedure the participants must report a certain fixed number of items (e.g. four) from the end of the list. According to Morris and Jones (British Journal of Psychology, 81, 111-121, 1990), the recalled items must be updated in memory as the presentation of the list progresses. Ruiz, Elosua and Lechuga (The Quarterly Journal of Experimental Psychology, 5, 887-905, 2005) noted that an active strategy implies an inhibition in memory of the final discarded items, and did not find results which supported this hypothesis. The aim of this study is to check whether or not participants adopt an active processing strategy in extreme conditions. Experiment 1 uses catch trials, which induce the participants not to discard the first items of the lists, and also short lists (of 4, 7, 8, 9 and 10 items); these could be considered optimal conditions for updating. However, it should also be pointed out that with an upper limit of 10 items per list, participants could try to memorise the whole list in most of the trials. One way to discourage this strategy is including lists well over span (e.g. 14-26 items). The purpose of Experiment 2 was to analyse the 10-item lists in two conditions: within a context of much longer lists (well over span) in most of the trials and within a context of shorter lists (data of Experiment 1). Results in both experiments, from the analysis of location errors, indicate that even in these conditions the participants do not seem to carry out the supposed active updating of the memory set. PMID- 17851685 TI - Transient occurrence of vasa-expressing cells in nongenital segments during embryonic development in the oligochaete annelid Tubifex tubifex. AB - The primordial germ cells (PGCs) in the oligochaete annelid Tubifex tubifex are mesodermal in origin and are located in the two midbody segments X and XI in which the testis and the ovary are formed, respectively. To identify a molecular marker for the Tubifex PGCs, we isolated the Tubifex homologue (Ttu-vas) of the Drosophila vasa gene. Using whole-mount in situ hybridization, we examined the spatial expression patterns of Ttu-vas from one-cell stage through juvenile stage. Ttu-vas messenger ribonucleic acid (RNA) is present as a maternal transcript distributed broadly throughout the early stages. Ttu-vas is expressed in all of the early cleavage blastomeres, in which Ttu-vas RNA associates with mitotic spindles and pole plasms. Expression of Ttu-vas gradually becomes restricted, first to teloblasts, then to their blast cell progeny comprising the germ bands (GBs), and finally to a set of large ventral cells (termed VE cells) in a variable set of midbody segments including the genital segments (X and XI). At the end of embryogenesis, VE cells are confined to genital segments where they are presumably germline precursors in the juvenile. Staining with a cross reacting anti-Vasa antibody suggested that VE cells express Ttu-vas protein to the same extent irrespective of their positions along the anteroposterior axis. A set of cell ablation experiments suggested that VE cells are derived from the mesodermal teloblast lineage and that the emergence of VE cells takes place independently of the presence of the ectodermal GBs that normally overlay the mesoderm. These results suggest that T. tubifex generates supernumerary presumptive PGCs during embryogenesis whose number is variable among embryos. PMID- 17851686 TI - Mixed germ cell sex cord-stromal tumours of the testis. PMID- 17851687 TI - COX-2 localization within plasma membrane caveolae-like structures in human lobular intraepithelial neoplasia of the breast. AB - Cyclooxygenase-2 (COX-2) is highly expressed in human intraepithelial neoplasia of the breast and takes part in the molecular pathway implicated in progression of breast cancer. Recently, we demonstrated that COX-2 protein is mainly located in plasma membrane of lobular intraepithelial neoplasia (LIN) cells suggesting a localization in caveolae-like structures. The aim of the present study is to establish subcellular locations of COX-2 and its colocalization with caveolin-1 (CAV-1) to caveolae structures in LIN. To establish a relationship between COX-2 and CAV-1, 39 LINs were studied by immunohistochemistry and confocal microscopy analysis. COX-2 and CAV-1 expression was observed respectively in 79.5 and in 94.9% of LIN studied. A positive correlation was found between membrane COX-2 staining pattern and CAV-1 expression, while no correlation was found between cytoplasm COX-2 staining pattern and CAV-1. Confocal analysis showed that COX-2 localized to plasma membrane was strictly associated to CAV-1 suggesting that an amount of COX-2 protein is placed in caveolae-like structures. Our results show that COX-2 is localized within caveolae compartment and colocalized with CAV-1 protein in LIN lesions. Because caveolae are rich in signaling molecules, this COX-2 compartment may play an important role in diverse breast cancer carcinogenesis processes. PMID- 17851688 TI - A new technique for feeding Pseudolynchia canariensis (Macquart, 1839) (Diptera, Hippoboscidae) under laboratory conditions. AB - The objective of this work was to present a new technique for feeding Pseudolynchia canariensis, reducing both fly-host and researcher-host contact. Flies obtained from pigeons caught in Juiz de Fora, MG, Brazil were housed in screen top test tubes and kept at 27 degrees C 80%RH. Three infestation-free pigeons were kept in screen cages as their food source. Pigeons were restrained on a wooden frame with test tube supports and a muzzle and twine to immobilize the head and wings, respectively. To minimize bird stress, both feeding wing and birds were alternated. Using this new technique, 60 flies were kept under laboratory conditions for an average of 12 +/- 17.8 days. This method allowed up to six flies per time to be fed in a short space of time, thus helping reduce stress for the animals used. PMID- 17851689 TI - Parasitic infection of the appendix as a cause of acute appendicitis. AB - The association between parasitic infection of the appendix and acute appendicitis has been widely investigated. The aim of this retrospective study was to evaluate the prevalence of parasitic infection of the appendix in a tropical area at southeast Brazil and to assess its possible relation to acute appendicitis in surgically removed appendices. Of the 1,600 appendectomies performed during a 10-year period, 24 (1.5%) were found to have helminths within the appendix. Enterobius vermicularis was observed in 23 of the 24 specimens (95.8%), and Taenia sp. was detected in only one case. Sixteen patients (66.7%) were less than 10 years old; 15 patients were male and nine female; 21 patients were white, and three were nonwhites. Pathologic analysis disclosed acute neutrophilic inflammation in the appendix wall in 12 of the 24 specimens and lymphoid hyperplasia in 10 of the 24 appendices. Gangrenous appendicitis was diagnosed in three cases, and peritonitis was found in 11 of the 24 infected appendices. The results of the present study indicate that E. vermicularis is the commonest worm found in the appendix and that its presence can cause pathologic changes ranging from lymphoid hyperplasia to acute phlegmonous inflammation with life-threatening complications like gangrene and peritonitis. PMID- 17851690 TI - Investigations on the biology, epidemiology, pathology and control of Tunga penetrans in Brazil. VI. Natural history of the infestation in laboratory-raised Wistar rats. AB - Tungiasis is endemic in many countries in Latin America, the Caribbean and sub Saharan Africa, and it is associated with severe morbidity. The pathophysiological and immunological characteristics of the ectoparasitosis are not well understood, and no effective therapy is currently available. The aim of this study was to describe the natural history of tungiasis in laboratory-raised Wistar rats. The rats were exposed in the laboratory to the parasite or were kept in a natural environment with an intense transmission of Tunga penetrans. The time course of the infestation was determined, and lesions were photographed, described clinically in detail and biopsied. Biopsies were examined histopathologically and by light and scanning electron microscopy. Based on these findings, the natural history of tungiasis in Wistar rats was described and divided in five stages. Our data show that the natural history of tungiasis in Wistar rats and humans is almost identical, except that in the animals, the basement membrane disrupts 5 days after penetration and provokes an intense infiltration of the dermis, while in humans, the basement membrane remains intact. The study indicates that the Wistar rat is an appropriate model for the study of clinical and pathological aspects of tungiasis. Using this model should enable a better understanding of the pathophysiology and immunology of the ectoparasitosis. PMID- 17851691 TI - Apoptosis-related gene expressions in hamsters re-infected with Opisthorchis viverrini and re-treated with praziquantel. AB - Our objective was to reveal whether host immune response in hamster opisthorchiasis post-praziquantel treatment could induce apoptotic cell death in inflammatory cells. We, therefore, investigated apoptosis-related gene expression in hamsters re-infected with Opisthorchis viverrini (OV) and re-treated with praziquantel. Hamsters were re-infected with OV metacercariae then re-treated with praziquantel. The expression of apoptosis-related genes (i.e. apoptosis gene Bcl-2 associated protein X [BAX], caspase 9, p53 and protein kinase B [PKB]) was detected by real-time reverse transcription-polymerase chain reaction. Histopathological analyses of liver tissues were performed by staining the sections with haematoxylin and eosin using light microscopy. The results show that BAX, Akt/PKB, p53 and caspase 9 expression levels were significantly increased on day 30 post-infection and at 6 h post-treatment and gradually decreased to a level near the uninfected control and at 24 h post-treatment, perhaps because of a decrease in inflammatory cells. Apoptotic cell death was observed at the nuclei of epithelial cells of the bile ducts and of T cells. Our results suggest that repeated infection with OV and re-treatment with praziquantel induces a host immune response that increases inflammatory cells, which in turn leads to increase, apoptosis-related gene expression in the short term post-treatment. PMID- 17851692 TI - The random versus fragile breakage models of chromosome evolution: a matter of resolution. AB - Conserved synteny--the sharing of at least one orthologous gene by a pair of chromosomes from two species--can, in the strictest sense, be viewed as sequence conservation between chromosomes of two related species, irrespective of whether coding or non-coding sequence is examined. The recent sequencing of multiple vertebrate genomes indicates that certain chromosomal segments of considerable size are conserved in gene order as well as underlying non-coding sequence across all vertebrates. Some of these segments lost genes or non-coding sequence and/or underwent breakage only in teleost genomes, presumably because evolutionary pressure acting on these regions to remain intact were relaxed after an additional round of whole genome duplication. Random reporter insertions into zebrafish chromosomes combined with computational genome-wide analysis indicate that large chromosomal areas of multiple genes contain long-range regulatory elements, which act on their target genes from several gene distances away. In addition, computational breakpoint analyses suggest that recurrent evolutionary breaks are found in "fragile regions" or "hotspots", outside of the conserved blocks of synteny. These findings cannot be accommodated by the random breakage model and suggest that this view of genome and chromosomal evolution requires substantial reassessment. PMID- 17851693 TI - Gender specific differences in levels of DNA methylation at selected loci from human total blood: a tendency toward higher methylation levels in males. AB - Abnormal patterns of DNA methylation are observed in many diseases such as tumors and imprinting disorders. Little is known about inter-individual and gender specific variations. Here, we report on accurate and sensitive quantitative measurements of methylation in DNA from total blood in 96 healthy human males and 96 healthy human females. Global methylation was estimated by studying two repetitive DNA elements, namely Line-1 and Alu repeats, while single loci were investigated for three differentially methylated regions (DMRs) at PEG3, NESP55 and H19 imprinted genes and two additional loci at Xq28 (F8 gene) and at 19q13.4 (locus between PEG3 and ubiquitin specific protease 29). We observed inter individual correlations in the degree of methylation between Alu and Line-1 repeats. Moreover, all studied CpGs showed slightly higher methylation in males (P < 0.0003-0.0381), with the exception of DMRs at imprinted genes (P = 0.0342 0.9616) which were almost equally methylated in both sexes with only a small tendency towards higher methylation in males. This observed difference could be due to the process of X chromosome inactivation or merely to the presence of an additional X chromosome in female cells or could be a result of downstream effects of sex determination. PMID- 17851694 TI - RAAS gene polymorphisms influence progression of pediatric hypertrophic cardiomyopathy. AB - Hypertrophic Cardiomyopathy (HCM) is a disease with variable rate of progression. Young age is an independent risk factor for poor outcome in HCM. The influence of renin-angiotensin-aldosterone (RAAS) genotype on the progression of HCM in children is unknown. Children with HCM (n = 65) were enrolled prospectively across two centers (2001-2005). All subjects were genotyped for five RAAS gene polymorphisms previously associated with LV hypertrophy (pro-LVH): AGT M235T, ACE DD, CMA-1903 A/G, AGTR1 1666 A/C and CYP11B2-344 C/T. Linear regression models, based on maximum likelihood estimates, were created to assess the independent effect of RAAS genotype on LV hypertrophy (LVH). Forty-six subjects were homozygous for <2 and 19 were homozygous for > or =2 pro-LVH RAAS polymorphisms. Mean age at presentation was 9.6 +/- 6 years. Forty children had follow-up echocardiograms after a median of 1.5 years. Indexed LV mass (LVMI) and LV mass z scores were higher at presentation and follow-up in subjects with > or =2 pro-LVH genotypes compared to those with <2 (P < 0.05). Subjects with > or =2 pro-LVH genotypes also demonstrated a greater increase in septal thickness (IVST) and in LV outflow tract (LVOT) obstruction on follow-up (P < 0.05). On multivariate analysis, a higher number of pro-LVH genotypes was associated with a larger effect size (P < 0.05). Pro-LVH RAAS gene polymorphisms are associated with progressive septal hypertrophy and LVOT obstruction in children with HCM. Identification of RAAS modifier genes may help to risk-stratify patients with HCM. PMID- 17851695 TI - IL-6 gene variation is associated with IL-6 and C-reactive protein levels but not cardiovascular outcomes in the Cardiovascular Health Study. AB - Interleukin-6 (IL-6) and C-reactive protein (CRP) levels increase with age and likely play a role in adverse health outcomes in older adults. The relationship between IL-6 gene tag single nucleotide polymorphisms (SNPs) and circulating IL-6 and CRP levels, cardiovascular disease (CVD) outcomes, and mortality in Caucasian (CA) and African American (AA) participants of the Cardiovascular Health Study (CHS) was evaluated using ANCOVA and Cox proportional hazards models. The minor allele of the promoter SNP 1510 and intronic SNP 3572 associates with significantly higher serum IL-6 and CRP levels in CA but not AA. The CRP association persisted after CA and AA populations were combined and after accounting for multiple comparisons. These associations did not carry through to cardiovascular disease outcomes. Decreased risk of stroke was identified in CA, with the minor allele of SNP 1111 (HRR 0.71, 95% CI 0.52, 0.95), P = 0.02, and increased risk of CVD and all-cause mortality (HRR 1.31, 95% CI 1.05-1.64) in AAs heterozygote for SNP 2989. While genetic variation in the IL-6 gene was associated with circulating IL-6 and especially with CRP concentrations in this study, there is little evidence for association between common IL-6 gene variation and adverse health outcomes in this population of older adults. PMID- 17851696 TI - Methods to impute missing genotypes for population data. AB - For large-scale genotyping studies, it is common for most subjects to have some missing genetic markers, even if the missing rate per marker is low. This compromises association analyses, with varying numbers of subjects contributing to analyses when performing single-marker or multi-marker analyses. In this paper, we consider eight methods to infer missing genotypes, including two haplotype reconstruction methods (local expectation maximization-EM, and fastPHASE), two k-nearest neighbor methods (original k-nearest neighbor, KNN, and a weighted k-nearest neighbor, wtKNN), three linear regression methods (backward variable selection, LM.back, least angle regression, LM.lars, and singular value decomposition, LM.svd), and a regression tree, Rtree. We evaluate the accuracy of them using single nucleotide polymorphism (SNP) data from the HapMap project, under a variety of conditions and parameters. We find that fastPHASE has the lowest error rates across different analysis panels and marker densities. LM.lars gives slightly less accurate estimate of missing genotypes than fastPHASE, but has better performance than the other methods. PMID- 17851697 TI - Novel human pathological mutations. Gene symbol: PRNP. Disease: dementia. PMID- 17851698 TI - Expression and cellular pattern of relaxin mRNA in porcine corpora lutea during pregnancy. AB - We developed an in situ hybridization method for detecting relaxin mRNA in the porcine corpus luteum (CL) by employing a non-radioactive probe and microwave fixation. We subsequently examined the expression and cellular patterns of relaxin mRNA in the CL during pregnancy and then evaluated whether relaxin mRNA was a factor limiting hormone production by the CL. Digoxigenin (DIG)-labeled RNA probes complementary to porcine relaxin mRNA were produced by in vitro transcription. The specificity was validated by showing, by Northern analysis, that the anti-sense probe hybridized to a 1.0-kb relaxin transcript in the CL. Microwave fixation (2-min irradiation in a conventional microwave oven) combined with DIG-labeled cRNA probes allowed precise and reliable analysis of relaxin mRNA, with superior retention of the mRNA and a higher resolving power. Application of this method to the porcine CL during pregnancy demonstrated that the relaxin mRNA level per cell and the percentage of mRNA-expressing cells increased as gestation progressed, with a marked decline near term. Northern analysis revealed the cellular pattern of relaxin mRNA localization, showing that the increase of relaxin mRNA with advancing pregnancy was attributable to an increase of both the cellular mRNA level and the percentage of mRNA-expressing cells. The present findings, taken together with known relaxin levels in the CL, reveal that changes of relaxin mRNA are correlated with changes of the hormone in the CL during pregnancy, suggesting that the relaxin level is determined by the amount of mRNA available for translation. PMID- 17851699 TI - Detecting the role of individual species for overyielding in experimental grassland communities composed of potentially dominant species. AB - Several studies have shown that the contribution of individual species to the positive relationship between species richness and community biomass production cannot be easily predicted from species monocultures. Here, we used a biodiversity experiment with a pool of nine potentially dominant grassland species to relate the species richness-productivity relationship to responses in density, size and aboveground allocation patterns of individual species. Aboveground community biomass increased strongly with the transition from monocultures to two-species mixtures but only slightly with the transition from two- to nine-species mixtures. Tripartite partitioning showed that the strong increase shown by the former was due to trait-independent complementarity effects, while the slight increase shown by the latter was due to dominance effects. Trait-dependent complementarity effects depended on species composition. Relative yield total (RYT) was greater than 1 (RYT>1) in mixtures but did not increase with species richness, which is consistent with the constant complementarity effect. The relative yield (RY) of only one species, Arrhenatherum elatius, continually increased with species richness, while those of the other species studied decreased with species richness or varied among different species compositions within richness levels. High observed/expected RYs (RYo/RYe>1) of individual species were mainly due to increased module densities, whereas low observed/expected RYs (RYo/RYe<1) were due to more pronounced decreases in module density (species with stoloniferous or creeping growth) or module size (species with clearly-defined plant individuals). The trade-off between module density and size, typical for plant populations under the law of constant final yield, was compensated among species. The positive trait independent complementarity effect could be explained by an increase in community module density, which reached a maximum at low species richness. In contrast, the increasing dominance effect was attributable to the species-specific ability, in particular that of A. elatius, to increase module size, while intrinsic growth limitations led to a suppression of the remaining species in many mixtures. PMID- 17851700 TI - Intermittent or daily administration of 1-alpha calcidol for nephrectomised infants on peritoneal dialysis? AB - Secondary hyperparathyroidism and renal osteodystrophy are major problems in patients with end-stage renal failure and may result in poor growth in children on dialysis. Whether vitamin D sterols should be given intermittently or daily remains a controversial issue. We studied 16 bilaterally nephrectomised infants with congenital nephrosis of the Finnish type (median age 0.54 years), all on peritoneal dialysis. Nine of them were receiving intermittent 1-alpha calcidol therapy and seven daily 1-alpha calcidol therapy. The target serum parathyroid hormone (PTH) level was 2-3 times the upper limit of normal (ULN). There were no statistically significant differences in PTH values between the groups (1.7-times vs 0.5-times the ULN at 3 months and 3.1-times vs 3.4-times the ULN at 6 months, respectively). The required weekly doses of 1-alpha calcidol were low, and there were no significant differences between the intermittent and daily groups (0.06 microg/kg vs 0.04 microg/kg at 3 months and 0.09 microg/kg vs 0.05 microg/kg at 6 months, respectively). The infants on intermittent 1-alpha calcidol showed significant catch-up growth during dialysis after nephrectomy relative to the infants on daily 1-alpha calcidol (-1.6 SD to -0.7 SD vs -1.4 SD to -1.0 SD, respectively; P < 0.05). Our results indicate that either intermittent or daily vitamin D analogue therapy, if started early, will prevent secondary hyperparathyroidism equally well in children on peritoneal dialysis (PD), but intermittent therapy might be more favourable for growth. PMID- 17851702 TI - MDCT diagnosis of ruptured tubal pregnancy with massive hemoperitoneum. AB - We report a case of ruptured tubal pregnancy with massive life-threatening hemoperitoneum. The 38 year-old woman presented with gynaecologic haemorrhage, pelvic pain and hypovolemic shock. Without any ambiguity, the diagnosis was directly made during contrast enhanced Multidetector Computed Tomography (MDCT). Massive hemoperitoneum with fresh blood clots in the hypogastric area, active free peritoneal extravasation of intravascular contrast material and dramatic peripheral enhancement, - "ring of fire" sign - of an adnexal cystic structure were the key signs. These signs must be known by the emergency radiologist because of the more and more use of CT as the first imaging modality in emergency departments particularly for patients with abdominal pain and presenting life threatening symptoms. PMID- 17851701 TI - The positive effect of posterolateral lumbar spinal fusion is preserved at long term follow-up: a RCT with 11-13 year follow-up. AB - INTRODUCTION: Few studies have investigated the long-term effect of posterolateral lumbar spinal fusion on functional outcome. AIM: To investigate the long-term result after posterolateral lumbar spinal fusion with and without pedicle screw instrumentation. METHODS: Questionnaire survey of 129 patients originally randomised to posterolateral lumbar spinal fusion with or without pedicle screw instrumentation. Follow-up included Dallas Pain Questionnaire (DPQ), Oswestry Disability Index (ODI), SF-36 and a question regarding willingness to undergo the procedure again knowing the result as global outcome parameter. RESULTS: Follow-up was 83% of the original study population (107 patients). Average follow-up time was 12 years (range 11-13 years). DPQ-scores were significantly lower than preoperatively in both groups (P < 0.005) and no drift towards the preoperative level was seen. No difference between the two groups were observed (instrumented vs. non-instrumented): DPQ Daily Activity mean 37.0 versus 32.0, ODI mean 33.4 versus 30.6, SF-36 PCS mean 38.8 versus 39.8, SF 36 MCS mean 49.0 versus 53.3. About 71% in both groups were answered positively to the global outcome question. Patients who had retired due to low back pain had poorer outcome than patients retired for other reasons, best outcome was seen in patients still at work (P = 0.01 or less in all questionnaires, except SF-36 MCS P = 0.08). DISCUSSION: Improvement in functional outcome is preserved for 10 or more years after posterolateral lumbar spinal fusion. No difference between instrumented fusion and non-instrumented fusion was observed. Patients who have to retired due to low back pain have the smallest improvement. PMID- 17851704 TI - [Notification of the Professional Association of German Internists Inc]. PMID- 17851703 TI - Choice determinants of the mobility in the Dutch health insurance market. AB - We estimate a Logit model for the choice determinants of the mobility in the Dutch market for health insurance in 2006. The results highlight that socio economic, geographical, and health-related factors matter in the decision to switch health care insurer. Moreover, previous contact with the insurer and the former type of health policy are also of influence. PMID- 17851708 TI - Different patterns of disease manifestations of parvovirus B19-associated reactive juvenile arthritis and the induction of antiphospholipid-antibodies. AB - Children with rheumatic oligo- and polyarthritis frequently establish persistent parvovirus B19 infections, which may be associated with the production of antiphospholipid antibodies. Reported in this paper are the data of five girls with polyarticular rheumatic diseases of different types and persistent parvovirus B19 infection associated in four cases with the presence of antibodies against phospholipids. Clinical parameters, virus load, and antiphospholipid-IgG levels were determined during an observation period up to 92 months. In two patients, erythema infectiosum preceded the development of arthritis and B19 viremia persisted. Two other girls showed antibodies against parvoviral structural proteins at time of the manifestation of the rheumatic disease. Subsequent samples also revealed persistent B19 infection. In the fifth patient, parvovirus B19-specific IgG antibodies were detected for the first time after 120 months of progressing disease at an age of 11 1/2 years. Five years later, quantitative polymerase chain reaction (PCR) revealed viral DNA. In a synovial tissue specimen subsequently obtained, parvovirus B19 structural proteins could be detected by immunohistochemistry. Three of five patients recovered completely without severe sequels. One patient is in remission under immunosuppressive therapy. The fifth patient suffers from progressive erosions despite intensive therapeutical efforts. In consequence, parvovirus B 19 should generally be taken into consideration as a trigger of various forms of juvenile arthritis and persistence of infection should be evaluated. PMID- 17851709 TI - Quality of life assessments with SF 36 in different musculoskeletal diseases. AB - The aim of this study is to evaluate comparatively the life quality of patients with knee osteoarthritis (KO), shoulder impingement syndrome(SIS), fibromialgia(FM), or osteoporosis(OP) using SF 36 and establish the impact of these diseases on quality of life (QoL). A total of 193 patients with one of the above-mentioned different diagnoses completed SF 36 scale. The diseases were compared to each other with SF 36 subgroups scores. There were significant differences among patients with KO and SIS, SIS and FM with respect to all SF 36 subgroups scores. According to these assessments, QoL of KO and FM patients was worst than that of SIS. The QoL scores of KO patients were worse than those of FM patients considering the physical function, while QoL scores of FM patients were lower than those of KO patients with respect to their general well-being. Scores of physical function and pain in KO patients were lower than those of OP patients. In domains of social functioning, emotional role, energy, pain, and general health condition QoL of FM patients was worse than that of OP patients. Quality of life of SIS patients was less affected than the patients of the other disease groups. In spite of their young age, FM patients appear to be the group with the worst quality of life scores. PMID- 17851710 TI - Diversity of assimilatory nitrate reductase genes from plankton and epiphytes associated with a seagrass bed. AB - Assimilatory nitrate reductase gene fragments were isolated from epiphytes and plankton associated with seagrass blades collected from Tampa Bay, Florida, USA. Nitrate reductase genes from diatoms (NR) and heterotrophic bacteria (nasA) were amplified by polymerase chain reaction (PCR) using two sets of degenerate primers. A total of 129 NR and 75 nasA clones from four clone libraries, two from each of epiphytic and planktonic components, were sequenced and aligned. In addition, genomic DNA sequences for the NR fragment were obtained from Skeletonema costatum and Thalassiosira weissflogii diatom cultures. Rarefaction analysis with an operational taxonomic unit cut-off of 6% indicated that diversity of the NR and nasA clone libraries were similar, and that sequencing of the clone libraries was not yet saturated. Phylogenetic analysis indicated that 121 of the 129 NR clones sequenced were similar to diatom sequences. Of the eight non-diatom sequences, four were most closely related to the sequence of Chlorella vulgaris. Introns were found in 8% of the Tampa Bay NR sequences; introns were also observed in S. costatum, but not T. weissflogii. Introns from within the same clone library exhibited close similarity in nucleotide sequence, position and length; the corresponding exon sequences were unique. Introns from within the same component were similar in position and length, but not in nucleotide sequence. These findings raise questions about the function of introns, and mechanisms or time evolution of intron formation. A large cluster of 14 of the 75 nasA sequences was similar to sequences from Vibrio species; other sequences were closely related to sequences from Alteromonas, alpha-proteobacteria and Marinomonas-like species. Biogeographically consistent patterns were observed for the nasA Tampa Bay sequences compared with sequences from other locations: for example, Tampa Bay sequences were similar to those from the South Atlantic Bight, but not the Barents Sea. The Tampa Bay NR clone libraries contained sequences that exhibited phylogenetic similarity with sequences from coastal New Jersey and Monterey Bay, USA. For both NR and nasA, the sequences formed phylogenetic clusters containing nitrate reductase gene fragments that were common to both plankton and epiphyte components, and sequences that were unique to just one component. The implication that some organisms may be differentially represented in epiphytic versus planktonic components of the community suggests that local environmental conditions may have ramifications for regulation of nitrate assimilation processes, community composition, and ecosystem function. PMID- 17851711 TI - Biliary complications after orthotopic liver transplantation: MRCP findings. AB - Orthotopic liver transplantation is a widely accepted treatment for end-stage liver disease and selected cases of hepatocellular carcinoma. Despite surgical progresses, biliary complications after transplantation remain a serious cause of morbidity, mortality, and graft dysfunction or failure in recipients. Early complications occur within a few weeks after transplantation and are mainly represented by bile leakage. Late complications, which become evident from 3 months to years, include strictures, stones, intraductal debris or sludge formation, kinking and ampullary dysfunction. Donor-to-recipient common bile duct disproportion has been reported as a borderline condition. Diagnosis is challenging because of the low specificity of clinical and biologic findings. Sonography does not provide projectional images of the biliary tract or direct evaluation of the anastomoses. Moreover, direct cholangiographic procedures have an unacceptable rate of complications to be used in patients with low clinical suspicion. Magnetic resonance cholangiography is a safe and accurate tool, playing an increasing role in the diagnosis and management of biliary complications. Heavily T2-weighted images provide panoramic, detailed evaluation of the biliary tract, showing biliary complications as a variable combination of bile duct dilatation, strictures, filling defects, fluid collections and peculiar morphologic changes, as described in this paper. PMID- 17851712 TI - The owl technique combined with the inferior pedicle in mastopexy. AB - Mastopexy patients usually are concerned with aesthetic outcomes, making the procedure a challenging one. Besides recreating a youthful, firm breast, a major concern is reducing the extent of scarring. Over recent decades, a number of short-scar techniques have emerged as alternatives. In 2002, Ramirez reported the owl technique, which combines the features of the periareolar and the vertical techniques. Nevertheless, the ideal technique also should improve shape and breast contour to withstand the test of time. The authors aim to show the results from combining the owl technique with the inferior pedicle for the treatment of patients who have mammary ptosis with or without hypertrophy. PMID- 17851713 TI - Aesthetic treatment of pectus excavatum: a new endoscopic technique using a porous polyethylene implant. AB - BACKGROUND: Pectus excavatum is the most frequent malformation of the rib cage. Functional aspects associated with this malformation often are absent even in adults not involved in competitive sports activities. Overall, these patients often live with extreme psychological discomfort when the malformations are minor. Traditionally, the correction of these malformations has been geared toward interventions that modify the architecture of the rib cage. However, all these interventions, even the most recent, involve considerably invasive major surgery. In fact, optimal results are not always achieved with corrective surgery using the insertion of silicone prosthesis, and patients often experience complications. METHODS: To correct intermediate and modest pectus excavatum in a stable manner and with the least amount of invasiveness, the authors developed a camouflage technique that uses porous prostheses made from high-density linear polyethylene. This material is generally used for reconstruction of the brain case. Between February 2001 and March 2006, in the I Unit of Plastic Surgery of the authors' Institute, 11 adult pectus excavatum patients with no previous cardiorespiratory symptoms underwent the authors' surgical technique. The average patient age was 29 years. RESULTS: Surgical repair was successful in all cases, and the average hospital stay was short. There were no complications during the follow-up period. The described approach repairs nonfunctional pectus excavatum in the adult with satisfying aesthetic and stable results, short hospital stay, and high patient popularity ratings. CONCLUSIONS: The best therapeutic option for pectus excavatum, especially with intermediate or moderate severity, is still controversial: thoracic surgery or camouflage surgery with implant? Trying to address those issues we propose a new technique by a multidisciplinary, not aggressive approach using a high density linear polyethylene implant and Omentus flap and the early analysis of our data. PMID- 17851714 TI - Microvascular transplantation of adipose tissue and serum level of adipocyte products. PMID- 17851715 TI - The histidinol phosphate phosphatase involved in histidine biosynthetic pathway is encoded by SCO5208 (hisN) in Streptomyces coelicolor A3(2). AB - Through the screening of a Streptomyces coelicolor genomic library, carried out in a histidinol phosphate phosphatase (HolPase) deficient strain, SCO5208 was identified as the last unknown gene involved in histidine biosynthesis. SCO5208 is a phosphatase, and it can restore the growth in minimal medium in this HolPase deficient strain when cloned in a high or low copy number vector. Moreover, it shares sequence homology with other HolPases recently identified in Actinobacteria. During this work a second phosphatase, SCO2771, sharing no homologies with SCO5208 and all so far described phosphatases was identified. It can complement HolPase activity mutation only at high copy number. Sequence analysis of SCO5208 and SCO2771, amplified from the HolPase mutant strain, revealed that SCO5208 shows a mutation in a conserved amino acid, whereas SCO2771 does not show any mutation. All these results show that S. coelicolor SCO5208, recently renamed hisN, is the HolPase involved in histidine biosynthesis. PMID- 17851717 TI - Critical role of P-selectin and lymphocyte function antigen-1 in radiation induced leukocyte-endothelial cell interactions in the colon. AB - PURPOSE: Radiation therapy is frequently used in treating different types of tumors, although associated with serious side effects, such as fibrosis and complicated diarrhea. This study was designed to define the adhesive mechanisms behind radiotherapy-induced leukocyte recruitment in the colon. METHODS: All mice, except control animals, were radiated with a single dose of 20 Gy. Mice were pretreated with an isotype-matched control antibody or a monoclonal antibody directed against P-selectin. In separate experiments, lymphocyte function antigen 1-deficient animals were used. Leukocyte rolling and firm adhesion were determined by use of inverted intravital fluorescence microscopy 16 hours after radiation. RESULTS: It was found that immunoneutralization of P-selectin reduced leukocyte rolling by 83 percent and adhesion by 87 percent in radiated mice. Moreover, radiation-induced leukocyte adhesion in LFA-1-deficient mice was decreased by 94 percent compared with wild-type animals. CONCLUSIONS: This study demonstrates that leukocyte rolling is mediated by P-selectin and that firm leukocyte adhesion is supported by lymphocyte function antigen-1 in radiation induced enteritis. Moreover, P-selectin-dependent leukocyte rolling is a precondition for subsequent leukocyte adhesion in radiation-induced intestinal injury. Thus, targeting P-selectin and/or lymphocyte function antigen-1 may protect against pathologic inflammation in the colon induced by radiotherapy. PMID- 17851716 TI - Optimising the use of computed radiography in pediatric chest imaging. AB - The objective of this study was to analyze image quality of chest examinations in pediatric patients using computed radiography (CR) obtained with a wide range of doses to suggest the appropriate parameters for optimal image quality. A sample of 240 chest images in four age ranges was randomly selected from the examinations performed during 2004. Images were obtained using a CR system and were evaluated independently by three radiologists. Each image was scored using criteria proposed by the European Guidelines on Quality Criteria in Pediatrics. Mean global scoring and scoring of individual criteria more sensitive to noise were used to evaluate image quality. Agfa dose level (DL) was in the range 1.20 to 2.85. It was found that there was not significant correlation (R < 0.5) between image quality and DL for any of the age ranges for either global score or for individual criteria more related to noise. The mean value of DL was in the ranges 1.9-2.1 for the four age bands. From this study, a DL value of 1.6 is proposed for pediatric CR chest imaging. This could yield a reduction of approximately a factor of 2.5 in mean patient entrance surface doses. PMID- 17851718 TI - Management of acute diverticulitis in the East Anglian region: result of a United kingdom regional survey. PMID- 17851719 TI - Percutaneous embolization of enterocutaneous fistulas. PMID- 17851720 TI - Early vs. delayed elective laparoscopic-assisted colectomy in sigmoid diverticulitis: timing of surgery in relation to the acute attack. AB - PURPOSE: The timing of elective surgery in acute sigmoid diverticulitis in relation to the acute attack is not clear. Early elective surgery during the same hospitalization as the acute attack or delayed surgery after an interval of several weeks are the options. This study was designed to evaluate the influence of timing on morbidity, conversion rate, histologic findings, and costs. METHODS: A total of 178 patients with elective laparoscopic-assisted sigmoid resections for diverticulitis between 1997 and 2005 were retrospectively assessed; 77 patients underwent early and 101 delayed surgery. Outcomes were surgical morbidity, conversion rate, histologic findings, and financial impact of timing. RESULTS: The two groups showed no significant difference apart from a higher body mass index in the delayed group (25.5 vs. 26.6 kg/m2, P = 0.035). Surgical morbidity was not significantly different. Conversion rate was significantly higher in the early group (P < 0.001). Converted patients had an increased surgical morbidity of 23.8 vs. 19.1 percent (P = 0.323) and hospitalization was significantly longer (13.5 vs. 10.5 days; P < 0.001). Histology revealed inflammation in 75.3 percent in the early group compared with 23.8 percent in the delayed group. Total treatment costs were not different between groups, whereas total earnings were higher in the delayed group resulting in a lower hospital deficit. CONCLUSIONS: Early elective surgery in patients with acute sigmoid diverticulitis results in a higher conversion rate. If patients respond to initial antibiotic therapy, delayed colectomy after an interval of six weeks or more is recommended. PMID- 17851721 TI - Physician-patient communication about colorectal cancer screening. AB - BACKGROUND: Despite the documented benefits of colorectal cancer screening, patient participation rates remain low. Physician recommendation has been identified as a significant predictor of screening completion. OBJECTIVE: The aim of this study is to investigate how primary care physicians perceive colorectal cancer screening communication tasks, as well as to explore the form and content of actual screening discussions. DESIGN: The research design includes a mailed physician survey and a separate observational study in a sample of videotaped medical encounters. PARTICIPANTS AND DATA SOURCES: The participants were 270 primary care physicians who completed a mailed questionnaire (57.9% response rate) and 18 physician-patient encounters that included discussions of colorectal cancer screening. MEASUREMENT: The questionnaire focused on perceived importance and accomplishment of communication tasks relevant to colorectal cancer screening. Two of the authors reviewed transcripts of videotaped physician encounters to determine whether the same communication tasks assessed in the survey were accomplished. Interrater reliability was high across all of the mutually exclusive coding categories (Kappa > .90). RESULTS: Physicians rated colonoscopy as the most important screening option to discuss; self-reports indicate that colonoscopy (84.8%) is more frequently mentioned than fecal occult blood test (FOBT; 49.4%), flexible sigmoidoscopy (34.1%), or computed tomography (CT) imaging (18.1%). Explaining benefits and risks, describing test procedure and frequency, eliciting patient preferences, and making a plan for screening were all viewed as very important. Self-reported accomplishment of these communication tasks was considerably higher than that observed in our separate videotape sample. CONCLUSION: Most physicians recognize and espouse the importance of recommending colorectal cancer screening to eligible patients. However, findings from both the physician survey and observational study suggest that physicians tend to overestimate the extent of discussions about screening. Interventions may be warranted to improve clinical practice. PMID- 17851722 TI - Extrahepatic portal vein aneurysm--report of six patients and review of the literature. AB - Extrahepatic portal vein aneurysm is a rare condition. We report six patients with extrahepatic portal vein aneurysm, four of whom were surgically treated. In addition, a review of the literature was performed to examine natural history, management, and outcomes regarding portal vein aneurysm. Patients seen at our institution with extrahepatic portal vein aneurysm greater than 1.9 cm in diameter were reviewed (1998 to 2006). There were five females and one male; median age was 66.5 (30-77). Computed tomography (CT) scan was utilized for diagnosis in all cases. The median diameter of the aneurysm was 4.7 cm (2.7-6.0). Indications for surgery included gallstone pancreatitis, mass effect on the adjacent duodenum, a peripancreatic mass, and liver cirrhosis. Three patients underwent aneurysm resection, and one patient had an orthotropic liver transplant. Two patients were managed with observation. The median follow-up from first presentation and surgery was 50 months (9-181) and 5 months (2-73), respectively. At last follow-up, five patients were alive with radiologically proven portal vein patency. One patient died 2 months after liver transplantation. There was no case of aneurysmal rupture. One patient had intramural thrombus at presentation that resolved with conservative treatment. This report suggests that symptomatic aneurysms can be safely resected with excellent patency. PMID- 17851724 TI - Clinical significance of the metastatic lymph-node ratio in early gastric cancer. AB - The metastatic lymph-node ratio has important prognostic value in gastric cancer; this study focused on its significance in early gastric cancer. In total, 1,472 patients with early gastric cancer underwent curative gastrectomy between 1992 and 2001. Of these, 166 (11.3%) had histologically proven lymph-node metastasis. Prognostic factors were identified by univariate and multivariate analyses. Metastasis was evaluated using the Japanese Classification of Gastric Carcinoma (JGC) and the Union Internationale Contre le Cancer/Tumor, Node, Metastasis (UICC/TNM) Classification. The metastatic lymph-node ratio was calculated using the hazard ratio. The cut-off values for the metastatic lymph-node ratio were set at 0, <0.15, >or=0.15 to <0.30, and >or=0.30. The numbers of dissected and metastatic lymph nodes were correlated, but the number of dissected lymph nodes and the metastatic lymph-node ratio was not related. The JGC and UICC/TNM classification demonstrated stage migration and heterogeneous stratification for disease-specific survival. The metastatic lymph-node ratio showed less stage migration and homogenous stratification. The metastatic lymph-node ratio may be a superior method of classification, which provides also accurate prognostic stratification for early gastric cancer patients. PMID- 17851723 TI - Treatment of unresectable cholangiocarcinoma with gemcitabine-based transcatheter arterial chemoembolization (TACE): a single-institution experience. AB - BACKGROUND: Survival for patients with unresectable cholangiocarcinoma is reported to range from only 5-8 months without treatment. Systemic chemotherapy has not been shown to significantly improve survival, but newer regimens involving gemcitabine have shown increased response rates. Transcatheter arterial chemoembolization (TACE) has been shown to prolong survival in hepatocellular carcinoma patients, but experience using TACE in the treatment of cholangiocarcinoma is limited. We report our experience treating cholangiocarcinoma with TACE using chemotherapeutic regimens based on the well tolerated drug gemcitabine. METHODS: Forty-two patients with unresectable cholangiocarcinoma were treated with one or more cycles of gemcitabine-based TACE at our institution. Chemotherapy regimens used for TACE included: gemcitabine only (n=18), gemcitabine followed by cisplatin (n=2), gemcitabine followed by oxaliplatin (n=4), gemcitabine and cisplatin in combination (n=14), and gemcitabine and cisplatin followed by oxaliplatin (n=4). RESULTS: Patients were 59 years of age (range 36-86) and received a median of 3.5 TACE treatments (range 1-16). Thirty-seven patients (88%) had central cholangiocarcinoma, and five (12%) had peripheral tumors. Nineteen patients (45%) had extrahepatic disease. Grade 3 adverse events (AEs) after TACE treatments were seen in five patients, whereas grade 4 AEs occurred in two patients. No patients died within 30 days of TACE. Median survival from time of first treatment was 9.1 months overall. Results did not vary by patient age, sex, size of largest initial tumor, or by the presence of extra-hepatic disease. Treatment with gemcitabine-cisplatin combination TACE resulted in significantly longer survival (13.8 months) compared to TACE with gemcitabine alone (6.3 months). CONCLUSIONS: Our report represents the largest series to date regarding hepatic-artery-directed therapy for unresectable cholangiocarcinoma and provides evidence in favor of TACE as a promising treatment modality in unresectable cholangiocarcinoma. Our results suggest that gemcitabine-based TACE is well tolerated and confers better survival when given in combination therapy (with cisplatin or oxaliplatin) for patients with unresectable cholangiocarcinoma. PMID- 17851725 TI - Isolation murine mesenchymal stem cells by positive selection. AB - Isolation and purification of mesenchymal stem cells (MSCs) from mouse via plastic adherent cultures is arduous because of the unwanted growth of hematopoietic cells and non-MSCs. In this work, homogenous populations of CD34(+) MSCs from mouse bone marrow were isolated via positive selection. For this purpose, C57Bl/6 mice were killed and bone marrow cells were aspirated before incubation with magnetic bead conjugated to anti-CD34 antibody. A sample of positively selected CD34(+) cells were prepared for flow cytometry to examine the expression of CD34 antigen and others were subcultured in a 25-cm(2) culture flask. To investigate the mesenchymal nature, the plastic adherent cultivated cells were induced to differentiate along osteoblastic and adipogenic lineages. Furthermore, the expression of some surface markers was investigated by flow cytometry. According to the result, purified populations of fibroblast-like CD34(+) cells were achieved in the first passage (1 wk after culture initiation). The cells expressed CD34, CD44, Sca-1, and Vcam-1 antigens (markers) but not CD11b and CD45. They were capable of differentiating into osteocytes and adipocytes. This study indicated that our protocol can result in the efficient isolation of homogenous populations of MSCs from C57BL/6 mouse bone marrow. We have shown that murine bone marrow-derived CD34(+) cells with plastic adherent properties and capability of differentiating into skeletal lineages in vitro are MSCs. PMID- 17851726 TI - Late-onset deep mesh infection after inguinal hernia repair. PMID- 17851727 TI - Long-term sequelae after 1,311 primary inguinal hernia repairs. AB - BACKGROUND: Aim of this study was to analyze long-term sequelae, risk factors, and satisfaction after inguinal hernia primary repair. METHODS: A postal questionnaire was mailed to all patients operated between January 1997 and December 2004 for inguinal hernia repair. Patients who had a lump in the groin and patients who experienced chronic problems were invited for a physical examination. Patients who reported having chronic pain were asked to fill out the short-form McGill Pain Questionnaire (SF-MPQ). RESULTS: Chronic pain was present in 18.1% of cases. The strongest risk factors were presence of recurrence, use of heavyweight mesh, and age younger than 66 years. By means of the SF-MPQ, we found that the pain reported by most patients was sensory-discriminative in quality, with "tender" and "aching" being the most common descriptors used. About 71.3% of replies used descriptors typical of nociceptive pain, 8.9% of neuropathic pain, and 19.8% of nociceptive plus neuropathic. Chronic pain was severe in 2.1% of patients and interfered with normal activities, work, and exercise. The cumulative recurrence rate was 2.1%. There was a strong correlation between lump and recurrence. Patients declared themselves satisfied with the result of the operation in 93.1% of cases. Due to chronic pain, 6.5% of patients were unsatisfied. CONCLUSIONS: This study demonstrates that the main problem after inguinal hernia repair remains chronic pain, which was the primary reason of dissatisfaction. The SF-MPQ is feasible and easy to administer to all patients and provides important information about qualitative features of the pain. PMID- 17851728 TI - Comparison of recurrence with lightweight composite polypropylene mesh and heavyweight mesh in laparoscopic totally extraperitoneal inguinal hernia repair: an audit of 1,232 repairs. AB - BACKGROUND: In Edinburgh a group of surgeons agreed to convert to a lightweight, composite mesh (Ultrapro-Ethicon) for totally extraperitoneal (TEP) inguinal hernia surgery. The aim of this study was to compare the outcome following the use of a new lightweight vs a standard heavyweight mesh during TEP hernia repair. METHODS: Patients undergoing TEP using lightweight (LWM) or heavyweight meshes (HWM) between March 2004 and March 2006 were identified from the Lothian Surgical Audit database. The patients who re-presented with recurrence of hernia were studied in greater detail. Date of re-attendance at a clinic with recurrence was used as a surrogate for date of recurrence. RESULTS: Two hundred and fifty one patients had 371 hernia repairs with LWM. A total of 16 (4.3%) recurred with a median follow-up of 14.5 months. A concurrent group of 326 patients had 425 repairs with standard mesh and have had 12 (2.82%) recurrences with a median follow-up of 22.4 months. A group of patients operated immediately prior to the introduction of LWM consisted of 328 patients who had 436 repairs using HWM, of whom 13 (2.98%) have recurred with a median follow-up of 43 months. Whilst there are no statistically significant differences in recurrence rates between these groups, we are concerned that the LWM group has the highest recurrence rate despite the shortest follow-up. CONCLUSION: In view of increased patient comfort, we continue to recommend LWM for laparoscopic inguinal hernia surgery but would recommend that, in larger hernias and possibly for all, the surgeon should improve mesh adhesion. PMID- 17851729 TI - Effect of suture material on tensile strength and complication rate in abdominal fascial defects repaired with acellular dermal matrix. AB - BACKGROUND: Repair of ventral hernias represents a challenging problem for surgeons. AlloDerm (LifeCell, Branchburg, NJ, USA), an acellular dermal matrix (ADM) product derived from cadaveric human skin, has gained in popularity in the management of abdominal hernias because of its ability to support neovascularization and therefore resist infection. Surgeons have traditionally used nonabsorbable suture when using ADM in this setting, perhaps because of concerns regarding wound strength. This study was undertaken to examine the influence of suture material on wound breaking strength and complication rates in abdominal wall defects closed with ADM. METHODS: Full-thickness abdominal defects were created in athymic rats and immediately repaired with an ADM interposition graft using either interrupted Prolene or Maxon suture. Complications were recorded over time and the animals were sacrificed at 1 month intervals. The abdominal repair complex was harvested and wound strength was measured using a tensiometer. RESULTS: There were no hernias in any of the groups. There were also no cases of major adhesions to the AlloDerm. Two rats in the Prolene group developed a stitch extrusion through the ventral skin. Wound breaking strength increased significantly from the second to third month after surgery in both suture groups (p=0.0000, LSD test). The breaking strength of the abdominal fascia ADM complex increased over the course of the experiment in both test groups, but no significant difference was found between the groups at any time point (p=0.3157). At 3 months, the breaking strength of the Prolene group and Maxon group was nearly identical (27.1 N +/- SD 7.4 and 29.7 N +/- SD 9.6, respectively). CONCLUSIONS: We were unable to identify a significant difference in breaking strength at the interface between ADM and normal, native fascia when using permanent versus resorbable sutures. PMID- 17851730 TI - Characterization of R peptide of murine leukemia virus envelope glycoproteins in syncytium formation and entry. AB - The C-terminal R peptide of ecotropic murine leukemia virus (MLV) envelope protein (Env) negatively controls membrane fusion activity. The R peptide cleavage during virion maturation activates its fusogenicity and is required for viral entry. We analyzed fusogenicity and transduction efficiency of mutant Env proteins of ecotropic, amphotropic, polytropic, and xenotropic MLVs. As the result, we found that the hydrophobic amino acid residues around the R peptide cleavage site are important for membrane fusion inhibition by the R peptide. In addition, we found that Env complexes with R peptide-truncated and -containing Env proteins have lower fusogenicity and transduction efficiency than those with the R-peptide-truncated Env alone, suggesting that efficient R peptide cleavage is required for efficient MLV vector transduction. The role of R peptide cleavage in amphotropic, polytropic, and xenotropic MLV infection has not been investigated. We found in this study that the R peptide cleavage is required for amphotropic, xenotropic, and polytropic MLV vector transduction, like with ecotropic MLV. The R-peptide-truncated Env proteins of the xenotropic and polytropic MLVs, however, had much lower fusogenicity than those of the ecotropic and amphotropic MLVs. These results provide valuable information for construction of efficient MLV vectors and for understanding the retroviral entry mechanism. PMID- 17851731 TI - Genetic variation of the norovirus GII-4 genotype associated with a large number of outbreaks in Chiba prefecture, Japan. AB - Between October and December, 2006, high activity of three genetically distinct norovirus GII-4 subtypes was observed in Chiba prefecture, Japan. One subtype was newly identified in this period and it was detected in 85% of outbreaks. PMID- 17851732 TI - Antiviral aptamers. AB - Aptamers are rare nucleic acid ligands, which can be concocted in the laboratory from the randomized pool of molecules by affinity and amplification processes. Aptamers have several properties as they can be applied complementarily to antibodies and have several advantages over antibodies. In the past, several aptamers have been selected with a view to develop antiviral agents for therapeutic applications. This review summarizes potent antiviral aptamers and their strategies to prevent the viral replication. PMID- 17851733 TI - Non-transferrin-bound iron in plasma following administration of oral iron drugs. AB - Non-transferrin-bound iron (NTBI) was detected in serum samples from volunteers with normal iron stores or from patients with iron deficiency anaemia after oral application of pharmaceutical iron preparations. Following a 100 mg ferrous iron dosage, NTBI values up to 9 muM were found within the time period of 1-4 h after administration whereas transferrin saturation was clearly below 100%. Smaller iron dosages (10 and 30 mg) gave lower but still measurable NTBI values. The physiological relevance of this finding for patients under iron medication has to be elucidated. PMID- 17851734 TI - Modulation of Sirt1 by resveratrol and nicotinamide alters proliferation and differentiation of pig preadipocytes. AB - Sirt1, a NAD(+)-dependent histone deacetylase, may regulate senescence, metabolism, and apoptosis. In this study, primary pig preadipocytes were cultured in DMEM/F12 medium containing 10% fetal bovine serum (FBS) with or without reagents affecting Sirt1 activity. The adipocyte differentiation process was visualized by light microscopy after Oil red O staining. Proliferation and differentiation of preadipocytes was measured using methylthiazolyldiphenyl tetrazolium bromide (MTT) and Oil red O extraction. Expression of Sirt1, FoxO1, and adipocyte specific genes was detected with semi-quantitive RT-PCR. The results showed that Sirt1 mRNA was widely expressed in various pig tissues from different developmental stages. Sirt1 mRNA was expressed throughout the entire differentiation process of pig preadipocytes. Resveratrol significantly increased Sirt1 mRNA expression, but decreased the expression of FoxO1 and adipocyte marker gene PPARgamma2. Resveratrol significantly inhibited pig preadipocyte proliferation and differentiation. Nicotinamide decreased the expression of Sirt1 mRNA, but increased the expression of FoxO1 and adipocyte specific genes. Nicotinamide greatly stimulated the proliferation and differentiation of pig preadipocytes. In conclusion, these results indicate that Sirt1 may modulate the proliferation and differentiation of pig preadipocytes. Sirt1 may down-regulate pig preadipocytes proliferation and differentiation through repression of adipocyte genes or FoxO1. PMID- 17851736 TI - Comparison of various mixtures of beta-chitin and chitosan as a scaffold for three-dimensional culture of rabbit chondrocytes. AB - With the use of a recently created chitosan neutral hydrogel, we have been able to create various mixtures of chitin and chitosan without changing their characteristics even at room temperature. The aim of this study was the initial comparison of various mixtures of beta-chitin and chitosan as a scaffold for rabbit chondrocyte culture. We created five types of sponges: pure beta-chitin, pure chitosan, 3:1, 1:1, and 1:3 beta-chitin-chitosan. The absorption efficiencies of chondrocytes in all five types of sponges were found to be around 98%. The mean concentrations of chondroitin sulfate were statistically different neither at week 2 nor at week 4 postculture between the types of sponges. The content of hydroxyproline in the beta-chitin sponge was significantly greater than in other sponges at week 4 postculture. From the histochemical and immunohistochemical findings, the cartilage-like layer in the chondrocytes-sponge composites of all five types of sponges was similar to hyaline cartilage. However, only immunohistochemical staining of type II collagen in the pure beta chitin sponge was closer to normal rabbit cartilage than other types of sponges. The pure beta-chitin sponge was superior to other sponges concerning the content of extracellular matrices of collagen. PMID- 17851735 TI - Characterization of collagen II fibrils containing biglycan and their effect as a coating on osteoblast adhesion and proliferation. AB - Collagen has been used as a coating material for titanium-based implants for bone contact and as a component of scaffolds for bone tissue engineering. In general collagen type I has been used, however very little attention has been focussed on collagen type II. Collagen-based coatings and scaffolds have been enhanced by the incorporation of the glycosaminoglycan chondroitin sulphate (CS), however the proteglycan biglycan, which is found in bone and contains glycosaminoglycan chains consisting of CS, has not been used as a biomaterial component. The study had the following aims: firstly, five different collagen II preparations were compared with regard to their ability to bind CS and biglycan and the changes in fibril morphology thereby induced. Secondly, the effects of biglycan on the adhesion of primary rat osteoblasts (rO) as well as the proliferation of rO, primary human osteoblasts (hO) and the osteoblast-like cell line 7F2 were studied by culturing the cells on surfaces coated with collagen II fibrils containing biglycan. Fibrils of the collagen II preparation which bound the most biglycan were used to coat titanium surfaces. Bare titanium, titanium coated with collagen II fibrils and titanium coated with collagen II fibrils containing biglycan were compared. It was found that different collagen II preparations showed different affinities for CS and biglycan. In four of the five preparations tested, biglycan reduced fibril diameter, however the ability of a preparation to bind more biglycan did not appear to lead to a greater reduction in fibril diameter. Fibrils containing biglycan promoted the formation of focal adhesions by rO and significantly enhanced the proliferation of hO but not of rO or 7F2 cells. These results should encourage further investigation of biglycan as a component of collagen-based scaffolds and/or coatings. PMID- 17851737 TI - Characterization of alkali-treated collagen gels prepared by different crosslinkers. AB - We have developed a naturally-derived crosslinker named malic acid derivative (MAD). In the present study, we prepared alkali-treated collagen (AlCol) gels with different crosslinkers including MAD and commercially available crosslinkers such as 1-ethyl-3-(3('-dimethylaminopropyl) carbodiimide (EDC) and glutaraldehyde (GA). There are named as AlCol-MAD, AlCol-EDC, and AlCol-GA. We then compared their physicochemical properties. The residual amino groups in AlCol-MAD were not detected at MAD concentrations higher than 30 mM. On the other hand, the residual amino groups in AlCol-EDC and AlCol-GA were detected at crosslinker concentrations of 30 mM. The swelling ratios of AlCol-MAD, AlCol-EDC, and AlCol GA decreased with increasing crosslinker concentration. Enzymatic degradation rate of AlCol-GA was slower than that of AlCol-MAD and AlCol-EDC. The cytotoxicity of MAD was clearly lower than that of EDC and GA. The number of adhered L929 on AlCol-MAD was higher than on AlCol-EDC and AlCol-GA after incubation for 1 day. After the culture for 3 and 7 days, excellent growth of L929 was observed on AlCol-MAD. These results suggested that MAD was excellent crosslinker for the reactivity with amino groups and cytocompatibility. Therefore, the resulting AlCol-MAD has potential for various biomedical applications like tissue engineering scaffolds and carrier for drug delivery systems. PMID- 17851738 TI - Comparison of albumin uptake in rat alveolar type II and type I-like epithelial cells in primary culture. AB - PURPOSE: To elucidate and compare the activity and mechanism of albumin uptake in primary cultured alveolar type II and type I-like epithelial cells. MATERIALS AND METHODS: Type II epithelial cells isolated from rat lungs were cultured for 2 days at 5 x 10(6) cells/35-mm dish or for 6 days at 2 x 10(6) cells/35-mm dish. The mRNA expression of marker genes and FITC-albumin uptake were examined. RESULTS: The cells cultured for 2 days exhibited cuboidal type II epithelial morphology with lamellar bodies inside the cells, while the cells cultured for 6 days exhibited squamous type I epithelial morphology. These morphological characteristics were consistent with the changes in mRNA expression pattern of marker genes. FITC-albumin uptake in both cells was temperature-dependent and was inhibited by metabolic inhibitors and bafilomycin A1. The rate of uptake was much higher in type II cells than type I-like cells. In both cells, FITC-albumin uptake was inhibited by clathrin mediated-endocytosis inhibitors, but not by caveolae mediated-endocytosis inhibitors. CONCLUSIONS: These findings indicate that albumin in alveolar lining fluid is internalized into type II and type I epithelial cells via clathrin-mediated endocytosis, and the rate of albumin uptake is higher in type II cells than type I cells. PMID- 17851739 TI - Contiguous X-chromosome deletion syndrome encompassing the BTK, TIMM8A, TAF7L, and DRP2 genes. AB - X-linked agammaglobulinemia (XLA) is characterized by low levels of B-lymphocytes with early-onset, recurrent, microbial infections occasionally causing neurological symptoms. We observed an atypical clinical course of XLA, complicated since early childhood with neurological impairment, progressive sensorineural deafness, and dystonia in six boys of four unrelated families. The neurologic symptoms suggested the diagnosis of Mohr-Tranebjaerg syndrome, caused by mutations in the TIMM8A gene, previously known as DDP1, and located centromerically of BTK. Deafness dystonia peptide (DDP1) participates in neurological development and is a part of the mitochondrial protein import pathway. Mutation analysis of the BTK gene revealed gross deletions of different lengths in all patients, in one case extending approximately 196 kb, including the genes TIMM8A, TAF7L, and DRP2. The most prominent clinical findings of this contiguous deletion syndrome are the combination of immunodeficiency and sensorineural deafness, which were present in all affected boys. The severity of symptoms, however, did not correlate with the extent of the deletion. PMID- 17851740 TI - Characterization of protein-protein interfaces. AB - We analyze the characteristics of protein-protein interfaces using the largest datasets available from the Protein Data Bank (PDB). We start with a comparison of interfaces with protein cores and non-interface surfaces. The results show that interfaces differ from protein cores and non-interface surfaces in residue composition, sequence entropy, and secondary structure. Since interfaces, protein cores, and non-interface surfaces have different solvent accessibilities, it is important to investigate whether the observed differences are due to the differences in solvent accessibility or differences in functionality. We separate out the effect of solvent accessibility by comparing interfaces with a set of residues having the same solvent accessibility as the interfaces. This strategy reveals residue distribution propensities that are not observable by comparing interfaces with protein cores and non-interface surfaces. Our conclusions are that there are larger numbers of hydrophobic residues, particularly aromatic residues, in interfaces, and the interactions apparently favored in interfaces include the opposite charge pairs and hydrophobic pairs. Surprisingly, Pro-Trp pairs are over represented in interfaces, presumably because of favorable geometries. The analysis is repeated using three datasets having different constraints on sequence similarity and structure quality. Consistent results are obtained across these datasets. We have also investigated separately the characteristics of heteromeric interfaces and homomeric interfaces. PMID- 17851741 TI - IF(1) distribution in HepG2 cells in relation to ecto-F(0)F (1)ATPsynthase and calmodulin. AB - F(0)F(1)ATPsynthase is now known to be expressed as a plasma membrane receptor for several extracellular ligands. On hepatocytes, ecto-F(0)F(1)ATPsynthase binds apoA-I and triggers HDL endocytosis concomitant with ATP hydrolysis. Considering that inhibitor protein IF(1) was shown to regulate the hydrolytic activity of ecto-F(0)F(1)ATPsynthase and to interact with calmodulin (CaM) in vitro, we investigated the subcellular distributions of IF(1), calmodulin (CaM), OSCP and beta subunits of F(0)F(1)ATPsynthase in HepG2 cells. Using immunofluorescence and Western blotting, we found that around 50% of total cellular IF(1) is localized outside mitochondria, a relevant amount of which is associated to the plasma membrane where we also found Ca(2+)-CaM, OSCP and beta. Confocal microscopy showed that IF(1) colocalized with Ca(2+)-CaM on plasma membrane but not in mitochondria, suggesting that Ca(2+)-CaM may modulate the cell surface availability of IF(1) and thus its ability to inhibit ATP hydrolysis by ecto F(0)F(1)ATPsynthase. These observations support a hypothesis that the IF(1) Ca(2+)-CaM complex, forming on plasma membrane, functions in the cellular regulation of HDL endocytosis by hepatocytes. PMID- 17851742 TI - Neuronal cell death in hepatic encephalopathy. AB - It is generally assumed that neuronal cell death is minimal in liver failure and is insufficient to account for the neuropsychiatric symptoms characteristic of hepatic encephalopathy. However, contrary to this assumption, neuronal cell damage and death are well documented in liver failure patients, taking the form of several distinct clinical entities namely acquired (non-Wilsonian) hepatocerebral degeneration, cirrhosis-related Parkinsonism, post-shunt myelopathy and cerebellar degeneration. In addition, there is evidence to suggest that liver failure contributes to the severity of neuronal loss in Wernicke's encephalopathy. The long-standing nature of the thalamic and cerebellar lesions, over 80% of which are missed by routine clinical evaluation, together with the probability that they are nutritional in origin, underscores the need for careful nutritional management (adequate dietary protein, Vitamin B(1)) in liver failure patients. Mechanisms identified with the potential to cause neuronal cell death in liver failure include NMDA receptor-mediated excitotoxicity, lactic acidosis, oxidative/nitrosative stress and the presence of pro-inflammatory cytokines. The extent of neuronal damage in liver failure may be attenuated by compensatory mechanisms that include down-regulation of NMDA receptors, hypothermia and the presence of neuroprotective steroids such as allopregnanolone. These findings suggest that some of the purported "sequelae" of liver transplantation (gait ataxia, memory loss, confusion) could reflect preexisting neuropathology. PMID- 17851743 TI - Lung epithelial cells modulate the inflammatory response of alveolar macrophages. AB - The goal of this study was to examine the effect of alveolar epithelial cells on inflammatory responses in macrophages. Lung epithelial cells (either rat RLE-6TN or human A549 cells) reduced LPS-induced NO production in alveolar macrophages (AM) in a contact-independent mechanism. The inhibitory effect of the epithelial cells was present already at the transcriptional level: LPS-induced inducible NO synthase (iNOS) expression was significantly smaller. Surfactant protein A (SP-A) induced NO production by alveolar macrophages was also reduced in the presence of A549 cells, though, by a different kinetics. LPS-induced interleukin-6 (IL-6) production (another inflammatory pathway) by alveolar macrophages was also reduced in the presence of RLE-6TN cells. These data suggest a role for lung epithelial cells in the complicated modulation of inflammatory processes, and provide an insight into the mechanism underlying. PMID- 17851744 TI - Silencing of African horse sickness virus VP7 protein expression in cultured cells by RNA interference. AB - RNA interference (RNAi) is the process by which double-stranded RNA directs sequence-specific degradation of homologous mRNA. Short interfering RNAs (siRNAs) are the mediators of RNAi and represent powerful tools to silence gene expression in mammalian cells including genes of viral origin. In this study, we applied siRNAs targeting the VP7 gene of African horse sickness virus (AHSV) that encodes a structural protein required for stable capsid assembly. Using a VP7 expression reporter plasmid and an in vitro model of infection, we show that synthetic siRNA molecules corresponding to the AHSV VP7 gene silenced effectively VP7 protein and mRNA expression, and decreased production of infectious virus particles as evidenced by a reduction in the progeny virion titres when compared to control cells. This work establishes RNAi as a genetic tool for the study of AHSV and offers new possibilities for the analysis of viral genes important for AHSV physiology. PMID- 17851745 TI - Genetic characterization of porcine circovirus type 2 (PCV2) from pigs in high seroprevalence areas in southeastern China. AB - Increasing evidences indicate that porcine circovirus type 2 (PCV2) is the causative agent of the post-weaning multisystemic wasting syndrome (PMWS). In this study, the prevalence of PCV2 infection in swine herds in southeastern China was investigated by ELISA and PCR, as well as the genetic characteristics by nucleic acid sequencing. Seroprevalence of PCV2 in samples collected from 89 swine herds was significantly higher by ELISA in post-weaning (54.1%) and growing piglets (49.9%) than that of suckling pigs (33.3%) with an average rate of 46.0% (819/1779). Seventy-eight cases out of 159 diseased pigs from these herds were PCV2 positive by PCR. Furthermore, the PCV2-positve rate at herds level in 2005 and 2006 were much higher than that in 2004 (65.63% or 69.23% vs. 32.26%, respectively), indicating that PCV-2 infection expanded rapidly over the past two years. To provide new insights into the extent of genetic heterogeneity of PCV2 isolates in southeastern China, the ORF2 genes of 27 isolates from the area during January 2004-March 2007 were sequenced and aligned. While closely related to each other with identity of 98.0-100%, these isolates displayed lower homologies to those from other regions of China (90.6-100%) or to some foreign isolates (91.3-98.9%). Alignment of deduced amino acid sequences of capsid protein identified two major hyper-variable regions (positions 53-91 and 185-215) in isolates obtained in this study, which were within or close to the putative epitope domains. The substitutions consequently resulted in higher hydrophilicity of the epitope region (positions 47-85). Phylogenetic analysis revealed two clusters of 48 isolates including those from Genbank: the large cluster I consisting of two subgroups and cluster II containing most of foreign isolates owing to the residue substitutions in epitope domains (amino acid positions 80, 86, 88 and 91). While the subgroup Ib contained all the isolates with ORF2 of 705 bp in length, the 27 isolates we sequenced were clustered exclusively in subgroup Ia together with some other Chinese strains. We conclude that PCV2 isolates prevailing in southeastern China were genetically different from those of other countries. PMID- 17851746 TI - Differences in gait across the menstrual cycle and their attractiveness to men. AB - We investigated variations in gait between women at high and at low conception probability, and how men rated those variations. Women participated in a motion capture study where we recorded the kinematics of their walking patterns. Women who were not using hormonal contraception (n = 19) repeated the study during the late follicular stage and the luteal stage of their menstrual cycle. Using a discriminant function analysis, we found significant differences in walking behavior between naturally cycling women at their follicular and luteal phases, with 71% of the walks classified correctly. However, there was no difference between walks of women in their follicular stage and women using hormonal birth control (n = 23). We compared structural and kinematic characteristics of the women's walking patterns that appeared to be characteristic of women in the specific conception risk groups, but found no significant differences. In a second study, 35 men rated the walks of women not using hormonal contraception as slightly more attractive during the luteal stage of the cycle compared to the late follicular stage. Thus, for women not using hormonal birth control, it would appear that some information regarding female fertility appears to be encoded in gait. PMID- 17851747 TI - Physical women, emotional men: gender and sexual satisfaction in midlife. AB - In late midlife, heterosexual women report markedly lower levels of sexual satisfaction than heterosexual men. This article explored the social factors contributing to this difference, using data from 1,035 sexually-active heterosexual adults, aged 40-59 years, who participated in the National Health and Social Life Survey (NHSLS). Conducted in 1992, NHSLS interviewed a nationally representative random sample of U.S. adults about diverse aspects of sexual life (Laumann et al., 1994, The social organization of sexuality: Sexual practices in the United States. Chicago: University of Chicago Press). Contrary to gender stereotypes, women's emotional satisfaction was closely associated with bodily sexual practices, whereas men's physical pleasure was linked to relational factors. Lower levels of sexual satisfaction at older ages appeared to stem from differences between the Baby Boom and older generations rather than from aging per se. PMID- 17851748 TI - Predictors of secondary abstinence in U.S. college undergraduates. AB - This study examined (1) the percentage of participants who practiced secondary sexual abstinence and (2) factors associated with its practice among a sample of U.S. college students. College undergraduate men and women (n = 1,133) in Texas completed a web-based survey assessing abstinence status and predictors of abstinent behavior. Results revealed that 12.5% of participants practiced secondary abstinence. Of eight variables, five significantly predicted secondary abstinence (following sexual initiation). Predictors were positive attitude toward abstinence, subjective norm supporting abstinence, greater religious ties, and previous negative sexual experiences. The fifth variable, participation in abstinence education, however, was associated with a significantly reduced likelihood of secondary abstinence. Fewer perceived barriers, less environmental manipulation (efforts to make physical and social environments supportive of abstinence), and greater religious ties significantly predicted self-efficacy for secondary abstinence. Findings provide an estimate of the percentage of participants who practiced secondary abstinence and suggest focal points for future research. PMID- 17851749 TI - Self-perceived effects of pornography consumption. AB - The self-perceived effects of "hardcore" pornography consumption were studied in a large representative sample of young adult Danish men and women aged 18-30. Using a survey that included the newly developed Pornography Consumption Effect Scale, we assessed participants' reports of how pornography has affected them personally in various areas, including their sexual knowledge, attitudes toward sex, attitudes toward and perception of the opposite sex, sex life, and general quality of life. Across all areas investigated, participants reported only small, if any, negative effects with men reporting slightly more negative effects than women. In contrast, moderate positive effects were generally reported by both men and women, with men reporting significantly more positive effects than women. For both sexes, sexual background factors were found to significantly predict both positive and negative effects of pornography consumption. Although the proportion of variance in positive effects accounted for by sexual background factors was substantial, it was small for negative effects. We discuss how the findings may be interpreted differently by supporters and opponents of pornography due to the reliance in this study on reported self-perceptions of effects. Nonetheless, we conclude that the overall findings suggest that many young Danish adults believe that pornography has had primarily a positive effect on various aspects of their lives. PMID- 17851750 TI - Negotiating a friends with benefits relationship. AB - Friends with benefits (FWB) refers to "friends" who have sex. Study 1 (N = 125) investigated the prevalence of these relationships and why individuals engaged in this relationship. Results indicated that 60% of the individuals surveyed have had this type of relationship, that a common concern was that sex might complicate friendships by bringing forth unreciprocated desires for romantic commitment, and ironically that these relationships were desirable because they incorporated trust and comfort while avoiding romantic commitment. Study 2 (N = 90) assessed the relational negotiation strategies used by participants in these relationships. The results indicated that people in FWB relationships most often avoided explicit relational negotiation. Thus, although common, FWB relationships are often problematic for the same reasons that they are attractive. PMID- 17851751 TI - Parent-child relationships and ADHD symptoms: a longitudinal analysis. AB - Evidence both from psychological research and clinical intervention studies suggests that there are bidirectional influences between overt child behavior problems and parent-child relations. Very little research however, has considered the pattern of relations that exists between Attention Deficit Hyperactivity Disorder (ADHD) and the parent-child relationship within a longitudinal context. Using a longitudinal community sample from the United Kingdom which included 194 school aged children (46% male and 54% female) and both parents, this study examined the relationship between child ADHD symptoms and displays of rejection in the parent-child relationship. These relationships were investigated separately for mothers and fathers using cross-lagged panel correlation and reciprocal effects analysis. Mothers and fathers reported on ADHD symptoms and children reported on their feelings of rejection in the mother-child and father child relationships. Results suggested differences in the direction of effects linking mother- and father-child rejection and child ADHD symptoms; with ADHD symptoms affecting the mother-child relationship and the converse pattern of effects noted for fathers. Implications for future research focusing on the link between ADHD symptoms and parent-child relationships are discussed. PMID- 17851752 TI - Children's affect expression and frontal EEG asymmetry: transactional associations with mothers' depressive symptoms. AB - Although parents and children are thought to influence one another's affect and behavior, few studies have examined the direction of effects from children to parents, particularly with respect to parental psychopathology. We tested the hypothesis that children's affective characteristics are associated with the course of mothers' depressive symptoms. Children's affect expression was observed during a series of mother-child interaction tasks, and children's resting frontal electroencephalogram (EEG) asymmetry was assessed in a psychophysiology laboratory. Mothers' depressive symptoms were assessed at two time points, approximately one year apart, at the mother-child interaction visits. Depressive symptoms increased over time for mothers with a history of childhood-onset depression whose children exhibited right frontal EEG asymmetry. Depressive symptoms were associated with high child negative affect at both time points for mothers whose children exhibited right frontal EEG asymmetry. Cross-lagged models with a subset of participants provided some evidence of both parent-to-child and child-to-parent directions of effects. Findings suggest that akin to other interpersonal stressors, children's affective characteristics may contribute to maternal depressive symptoms. PMID- 17851753 TI - Ovarian protection with goserelin during adjuvant chemotherapy for pre-menopausal women with early breast cancer (EBC). AB - PURPOSE: Ovarian failure and infertility following adjuvant chemotherapy for early breast cancer are major concerns for some young women. Techniques for oocyte harvesting are associated with delay in starting treatment, potentially undesirable estrogen stimulation and a relatively low success rate. We report an audit of our experience with the luteinising hormone-releasing hormone agonist, goserelin, to achieve transient ovarian suppression during chemotherapy as a means of preserving ovarian function. PATIENT AND METHODS: Pre-menopausal women were offered goserelin 3.6 mg by subcutaneous injection every 28 days during chemotherapy, starting 0-14 days prior to treatment. The primary end-point was recovery of menstruation. Serum luteinising hormone, follicle stimulating hormone and oestradiol were measured at recovery of menstruation or at first year follow up if amenorrhoea persisted. Subsequent pregnancies were recorded. RESULTS: Fifty one evaluable women were audited. Amenorrhoea occurred in all but one. All received combination anthracycline-containing chemotherapy regimens with a mean cumulative cyclophosphamide dose of 3.9 g/m(2). Forty-five (90%) recovered menstruation during the first year of follow-up; mean time to recovery 5 months. Eight pregnancies in 10 women attempting this so far. CONCLUSION: Using goserelin concurrently with chemotherapy is associated with a high rate of ovarian function preservation. PMID- 17851754 TI - Post-diagnosis statin use and breast recurrence sites in early stage breast cancer survivors. PMID- 17851755 TI - Standardization of pathologic complete response rates in breast cancer treatment. PMID- 17851756 TI - Lymphedema in women with breast cancer: characteristics of patients screened for a randomized trial. AB - INTRODUCTION: Accrual rates for a randomized trial of decongestive therapy in breast cancer patients with lymphedema were lower than anticipated. In two centres, patients presenting to lymphedema clinic were screened for eligibility to understand the accrual process and help define the patient population. MATERIALS AND METHODS: All breast cancer patients presenting to two lymphedema clinics in regional cancer centres were screened for study entry. Circumferential arm measurements were taken and volumes calculated. Patients were then screened for trial eligibility. All report forms were sent to the trial coordinating centre. RESULTS: A total of 408 patients were screened. Median arm volume excess was 239 ml (9.5%). One third of patients had little or no excess volume. Only 28.3% of patients had sufficient excess volume for trial eligibility. Of these, a significant number of patients were excluded because of active malignancy or previous decongestive therapy. CONCLUSIONS: The finding of moderate to severe lymphedema observed in clinics screening for trial eligibility was less than expected. The natural history of lymphedema in breast cancer patients is potentially changing. Some patients may be presenting with sensory changes suggestive of lymphedema but due to other causes, such as nerve disruption following axillary dissection. PMID- 17851757 TI - A phase II, randomized, blinded study of the farnesyltransferase inhibitor tipifarnib combined with letrozole in the treatment of advanced breast cancer after antiestrogen therapy. AB - BACKGROUND: This study assessed the clinical efficacy of the farnesyltransferase inhibitor, tipifarnib, combined with letrozole in patients with advanced breast cancer and disease progression following antiestrogen therapy. PATIENTS AND METHODS: Postmenopausal women with estrogen-receptor-positive advanced breast cancer that had progressed after tamoxifen were given 2.5 mg letrozole once daily and were randomly assigned (2:1) to tipifarnib 300 mg (TL) or placebo (L) twice daily for 21 consecutive days in 28-day cycles. The primary endpoint was objective response rate. RESULTS: Of 120 patients treated with TL (n = 80) or L (n = 40), 113 were evaluable for response. Objective response rate was 30% (95% CI; 20-41%) for TL and 38% (95% CI; 23-55%) for L. There was no significant difference in response duration, time to disease progression or survival. Clinical benefit rates were 49% (TL) and 62% (L). Tipifarnib was generally well tolerated; a higher incidence of drug-related asymptomatic grade 3/4 neutropenia was observed for TL (18%) than for L (0%). Tipifarnib population pharmacokinetics were similar to previous studies, with no significant difference in trough letrozole concentrations between the TL and L groups. CONCLUSIONS: Adding tipifarnib to letrozole did not improve objective response rate in this population of patients with advanced breast cancer. PMID- 17851758 TI - Breast cancer in elderly women. Optimizing the treatment. AB - The elderly population is on the rise. Breast cancer is the most common cancer in western women and its incidence increases with age. Despite the epidemiological burden of this condition, there is a lack of knowledge regarding the management of older patients, as treatment planning is mainly based on personal preferences rather than hard data. Older women are often offered sub-optimal treatment when compared to their younger counterpart at any particular stage. This is due to various reasons, including the lack of scientific evidence from well-conducted clinical trials. Reluctance to prescribe systemic treatments may be explained by the complexity of cost-benefit evaluations in such patients. It is also an ethical dilemma to decide how aggressive one should be when it comes to treat cancer in the elderly in view of the higher rate of cognitive impairment and specific patients' expectations. This paper reviews the currently available evidence and attempts presenting and discussing chemoprevention of breast cancer, risk and benefit of hormone replacement therapy and the various treatment options for older women with breast cancer. PMID- 17851759 TI - A phase II study of pemetrexed and carboplatin in patients with locally advanced or metastatic breast cancer. AB - BACKGROUND: Pemetrexed and carboplatin have demonstrated activity in breast cancer. Their potential synergism in experimental models and the proven efficacy of pemetrexed/platinum in other indications make pemetrexed/carboplatin an attractive combination in breast cancer. Thus, this two-stage, sequential, open label, multicenter, phase II study assessed the efficacy and safety of pemetrexed plus carboplatin as first-line therapy in patients with locally advanced breast cancer (LABC) or metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients >or= 18 years with a histologic/cytologic diagnosis and no prior chemotherapy for LABC or MBC received pemetrexed 600 mg/m(2) and carboplatin AUC 5.0 on day 1 every 21 days with folic acid and vitamin B(12) supplementation. RESULTS: From June 2003 to April 2005, 50 patients with stage IIIB (30.0%) and stage IV (70.0%) disease were enrolled at 3 study centers. Twenty-eight percent of patients previously received adjuvant chemotherapy, 46.0% had visceral metastases, and 36.0% had >or=3 organs involved. Partial responses (RECIST criteria) were achieved in 27 (54.0%) patients (ORR = 54.0%; 95% CI, 39.3-68.2%). The median response duration was 11.1 months (95% CI, 6.5-14.0 months) and the median time to disease progression was 10.3 months (95% CI, 8.3-14.6 months). CTC hematologic toxicities were grade 3/4 neutropenia (58.0%/28.0%) and grade 3 thrombocytopenia (10.0%) and anemia (18.0%). Two (4.0%) patients had febrile neutropenia, 1 of whom died. No grade 4 non-hematologic toxicities occurred. Grade 3 non hematologic toxicities were ALT (4.0%) and AST elevation, and edema, fatigue, pruritus, rash/desquamation, and renal toxicity (2.0% each). CONCLUSIONS: Results of this study suggest that the combination of pemetrexed and carboplatin has promising efficacy and an acceptable safety profile. Further assessment of this combination in a randomized trial of various breast cancer patient populations is warranted. PMID- 17851760 TI - Antibodies to 46-kDa retinal antigen in a patient with breast carcinoma and cancer-associated retinopathy. AB - Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome usually associated with small-cell lung carcinoma and serum autoantibodies against recovering. We report the breast cancer woman with visual impairments and electrophysiological abnormalities characteristic of CAR. Her serum contained high-titer antibodies against alpha-enolase but not against other retinal proteins. This suggests that anti-enolase antibodies could be responsible for the development of CAR symptoms. PMID- 17851761 TI - Extracellular matrix, Rac1 signaling, and estrogen-induced proliferation in MCF-7 breast cancer cells. AB - Estrogen receptor positive (ER+), estrogen (E) responsive MCF-7 breast cancer cells cultured on the extracellular matrix (ECM) protein laminin (LM), exhibit significantly reduced E-induced proliferation compared with cells cultured on collagen I (Col I) that is not due to a loss of ER. Based on reported differences in integrin-activated pathways on Col I vs. LM, we investigated the potential role of Rac1/c-jun-N-terminal kinase (JNK) activation and downstream regulation of cyclin D1 by E on Col I vs.LM. E-induced proliferation was increased on LM in MCF-7 cells expressing constitutively active Rac1 (CA Rac1) and decreased in dominant negative Rac1-(DN Rac1) expressing cells on Col I. siRNA knockdown established the specificity and requirement for Rac1 activation for E-induced regulation of cyclin D1. More robust c-Jun activation occurred on Col I than on LM and E-induced proliferation was abolished after treatment with a JNK inhibitor. These results provide evidence that Rac1/JNK/c-Jun activation promotes E-induced proliferation on Col I and reduced Rac1/JNK/c-Jun activation on LM contributes significantly to reduced E-induced proliferation in MCF-7 cells on LM. These results identify a novel role for extracellular matrix (ECM)-integrin regulation of Rac1-JNK pathway in E-regulated proliferation in ER+ breast cancer cells. These findings suggest that tumor stromal environment, i.e., ECM composition, may contribute to loss of E regulation in ER+ breast cancers. Defining molecular markers for early identification of ER+ tumors that are ER+ but antiestrogen resistant would allow the design and use of alternative therapies to inhibit tumor growth and improve survival. PMID- 17851762 TI - Genetic variants in the H2AFX promoter region are associated with risk of sporadic breast cancer in non-Hispanic white women aged G [rs643788], -1420G > A [rs8551], and -1187T > C [rs7759] in the H2AFX promoter region and 1057C > T [rs7350] in the 3' untranslated region (UTR)) in 467 patients with sporadic breast cancer and 488 cancer-free controls. All female subjects were non-Hispanic whites aged T polymorphism. Therefore, we believe that H2AFX promoter polymorphisms may contribute to the etiology of sporadic breast cancer in young non-Hispanic white women. Larger association studies and related functional studies are warranted to confirm these findings. PMID- 17851763 TI - The prevalence of BRCA1 and BRCA2 germline mutations in high-risk breast cancer patients of Chinese Han nationality: two recurrent mutations were identified. AB - To have an overview of the role of BRCA1 and BRCA2 genes among Chinese high-risk breast cancer patients, we analyzed 489 such high-risk breast cancer patients from four breast disease clinical centers in China, by using PCR-DHPLC or SSCP DNA sequencing analysis. Allelotype analysis was done at five short tandem repeat (STR) markers in or adjacent to BRCA1 on the recurrent mutation carriers. For those analyzed both genes, 8.7% of early-onset breast cancer cases and 12.9% of familial breast cancer cases had a BRCA1 or BRCA2 mutation, as compared with the 26.1% of cases with both early-onset breast cancer and affected relatives. For those reporting malignancy family history other than breast/ovarian cancer, the prevalence of BRCA1/2 mutation is about 20.5%, and it was significantly higher than the patients only with family history of breast/ovarian cancer (P = 0.02). The family history of ovarian cancer (26.7% vs. 11.9%) and stomach cancer (23.8% vs. 11.8%) doubled the incidence of BRCA1/2, but the difference did not reach the statistical significance. Two recurrent mutations in BRCA1, 1100delAT and 5589del8, were identified. The recurrent mutations account for 34.8% BRCA1 mutations in our series. Similar allelotypes were detected in most STR status for those harboring the same mutations. The BRCA1 associated tumors were more likely to exhibit a high tumor grade, negative C-erbB-2/neu status and triple negative (ER, PgR and C-erbB-2/neu negative) status (P < 0.05). We recommended the BRCA1 and BRCA2 genetic analysis could be done for high-risk breast cancer patient in Chinese population, especially for those with both early-onset breast cancer and affected relatives. There may be some degree of shared ancestry for the two recurrent BRCA1 mutations in Chinese. PMID- 17851764 TI - Intra-hepatic Mitomycin C bolus infusion in the treatment of extensive liver metastases of breast cancer. AB - BACKGROUND: In the treatment of extensive liver metastasis of breast cancer (LMBC), locally administered Mitomycin C (MMC) to the liver might be an effective approach with limited toxicity. PATIENTS AND METHODS: We retrospectively reviewed the records of 30 patients with LMBC treated with intra-hepatic MMC at our institution. MMC (12 mg) was administered by transcatheter bolus infusion into the hepatic arteries every 4 weeks. Tumour response according to RECIST criteria, progression free survival (PFS), overall survival (OS) and duration of response (DR) were used to evaluate efficacy. RESULTS: There was a local response in the liver and a global response in respectively 33 and 26%. The median PFS, DR and OS were 3, 4 and 7 months, respectively. There was more benefit in patients without documented metastases outside the liver and without severe liver dysfunction. Thrombocytopenia, leucocytopenia and an allergic reaction were observed after MMC administration in 20 (67%), 12 (40%) and 4 patients (13%), respectively. CONCLUSION: Intra-hepatic MMC bolus infusion as treatment of extensive LMBC is associated with limited toxicity and has a significant response rate in the liver. Prospective investigations are required to define the place of this modality for treating patients with breast cancer liver metastases. PMID- 17851765 TI - Symptom measurement in the Breast Cancer Prevention Trial (BCPT) (P-1): psychometric properties of a new measure of symptoms for midlife women. AB - PURPOSE: To evaluate scalability of a symptom scale administered to women enrolled in the Breast Cancer Prevention Trial (BCPT) (P-1) conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP). PATIENTS AND METHODS: Responses of 11,064 women recruited into a study of 20 mg daily tamoxifen versus placebo to prevent breast cancer in high-risk women were analyzed. Exploratory factor analyses of the 12 month data were conducted on a random subset of 4,000 women to estimate the factor structure. Baseline data on these same 4,000 women were analyzed to confirm the structure. The remaining sample was divided randomly into two data sets. Data on each set were then grouped by age (35-49, 50-59, or > or = 60 years) and treatment (tamoxifen or placebo) to corroborate these analyses. Correlations between the obtained symptom clusters and two standard instruments (SF-36 and CES-D) were examined. Content analysis of open-ended responses was also conducted. RESULTS: Eight clinically interpretable clusters of symptoms were identified and confirmed: Cognitive symptoms, musculoskeletal pain, vasomotor symptoms, nausea, sexual problems, bladder problems, body image, and vaginal symptoms. Scoring for each scale represented by these eight clusters is provided. Content analysis of open-ended responses suggested four items that are additional candidates: fatigue, back problems, abdominal pain, and leg/foot cramps or pain. CONCLUSIONS: Symptoms associated with hormone therapy for breast cancer can vary. Nevertheless, the BCPT Eight Symptom Scale (BESS) can be clustered into clinically relevant and reproducible factors that may be useful in future outcomes research. PMID- 17851766 TI - First evidence of polyploidy in Psylloidea (Homoptera, Sternorrhyncha): a parthenogenetic population of Cacopsylla myrtilli (W. Wagner, 1947) from northeast Finland is apomictic and triploid. AB - This paper reports results of the first cytogenetic study of parthenogenetic psyllids, carried out on an asexual population of the holarctic species Cacopsylla myrtilli W. Wagner from northeast Finland. Preparations of mature eggs extracted from females revealed 39 univalent chromosomes in prophase and metaphase cells. Hence, female meiosis is of apomictic type and replaced by a modified mitosis. The karyotype consists of 3n = 39 (36 + XXX). Clearly, the population is triploid, the haploid number being n = 12 + X as characteristic of the genus Cacopsylla as a whole. As typical for Psylloidea, the chromosomes are holokinetic, only slightly varying in size and without any visible markers, rendering impossible the precise identification of triplets of homologous chromosomes in the triploid complement. The distribution of bisexual and parthenogenetic populations of C. myrtilli throughout the world is briefly given, and a possible origin of the triploid parthenogenetic population is discussed. PMID- 17851767 TI - Search for effective natural enemies of Tetranychus evansi (Acari: Tetranychidae) in northwest Argentina. AB - The mite Tetranychus evansi Baker & Pritchard (Tetranychidae) probably originated in South America. Because of its importance as a tomato pest in Africa, an extensive project has been conducted to detect potentially effective natural enemies in South America for the classical biological control of the pest in Africa. A search for the natural enemies of T. evansi was conducted in the Province of Tucuman, northwestern Argentina, in December 2004, and this report describes the results. One hundred predatory mites of the family Phytoseiidae referring to 11 species were collected on 11 examined species of solanaceous plants. The most abundant phytoseiid species collected were Neoseiulus californicus (McGregor) and Euseius concordis (Chant). Adults and immatures of those species, as well as of Neoseiulus idaeus Denmark & Muma, Phytoseiulus fragariae Denmark & Schicha and Proprioseiopsis cannaensis (Muma) were found in association with T. evansi, suggesting that they were developing on the pest. However, because of the possible biological differences between populations of a given species, biological studies evaluating T. evansi as a prey for those predators seem desirable. PMID- 17851768 TI - Laboratory rearing of Theileria annulata-free Hyalomma anatolicum anatolicum ticks. AB - Hyalomma anatolicum anatolicum is a three-host tick which transmits Theileria annulata infection in Indian cattle. Laboratory rearing of ixodid ticks is an essential requirement of any laboratory engaged with research on ticks and tick borne diseases. The Entomology laboratory of Indian Veterinary Research Institute is fully equipped with all the facilities and skilled manpower to maintain a homogenous H. a. anatolicum population throughout the year. The continuous supply of eggs, larvae and adults of H. a. anatolicum is maintained to meet out the demand of different experiments viz., preparation of tick antigens for immunization of animals, experimental challenge, isolation of genomic DNA and RNA. Maintenance of a H. a. anatolicum colony free of T. annulata infection is imperative for the experimental challenge infestation on cross-bred (Bos indicus x B. taurus) calves, in order to prevent the transmission of T. annulata infection to the experimental animals. A system has been developed in the laboratory in which the larvae of H. a. anatolicum were fed on New Zealand white rabbits and the dropped fed nymphs molted to adults are fed on cross-bred calves free of T. annulata infection. This synthetic cycle prevents the transstadial transmission of T. annulata as the rabbits are unsusceptible to T. annulata infection and only the adults were fed on cross-bred animals. Moreover, absence of transovarial transmission of T. annulata prevents the chance of carry over infection to experimental animals in the next cycle. PMID- 17851770 TI - Boron intake and prostate cancer risk. AB - INTRODUCTION: Experimental studies suggest that boron may prevent prostate cancer. Only one small epidemiological study has been conducted of boron, which found that those in the highest quartile of boron intake had less than half the risk of prostate cancer versus those in the lowest quartile. METHODS: We evaluated the association between boron intake and prostate cancer within the VITamins And Lifestyle (VITAL) cohort. A total of 35,244 men completed the baseline supplement and food frequency questionnaire (FFQ) in 2000-2002. A boron database was constructed from published sources to estimate boron intake from the FFQ and from multivitamins. A total of 832 men developed prostate cancer from baseline to 31 December 2004. RESULTS: Dietary boron intake and total boron intake from diet plus multivitamins were not associated with prostate cancer risk. The hazard ratio of prostate cancer for those in the highest versus lowest quartile of total boron intake was 1.17 (95% CI 0.85, 1.61). This risk did not vary by prostate cancer stage or Gleason score. Furthermore, none of the foods high in boron content was associated with a decreased risk of prostate cancer. DISCUSSION: This cohort study provides no evidence for a preventive role of boron intake on prostate cancer. Since few studies exist on this topic, future research is needed to better elucidate any role that boron may play in the prevention of prostate cancer. PMID- 17851771 TI - Lactation performance of transgenic goats expressing recombinant human butyryl cholinesterase in the milk. AB - The production of recombinant proteins in the milk of transgenic animals has attracted significant interest in the last decade, as a valuable alternative for the production of recombinant proteins that cannot be or are inefficiently produced using conventional systems based on microorganisms or animal cells. Several recombinant proteins of pharmaceutical and biomedical interest have been successfully expressed in high quantities (g/l) in the milk of transgenic animals. However, this productivity may be associated with a compromised mammary physiology resulting, among other things, from the extraordinary demand placed on the mammary secretory cells. In this study we evaluated the lactation performance of a herd of 50 transgenic goats expressing recombinant human butyryl cholinesterase (rBChE) in the milk. Our findings indicate that high expression levels of rBChE (range 1-5 g/l) are produced in these animals at the expense of an impaired lactation performance. The key features characterizing these transgenic performances were the decreased milk production, the reduced milk fat content which was associated with an apparent disruption in the lipid secretory mechanism at the mammary epithelium level, and a highly increased presence of leukocytes in milk which is not associated with mammary infection. Despite of having a compromised lactation performance, the amount of rBChE produced per transgenic goat represents several orders of magnitude more than the amount of rBChE present in the blood of hundreds of human donors, the only other available source of rBChE for pharmaceutical and biodefense applications. As a result, this development constitutes another successful example in the application of transgenic animal technology. PMID- 17851769 TI - Olfactory epithelium progenitors: insights from transgenic mice and in vitro biology. AB - The rodent olfactory epithelium (OE) is capable of prolonged neurogenesis, beginning at E10 in the embryo and continuing throughout adulthood. Significant progress has been made over the last 10 years in revealing the signals that drive induction, differentiation and survival of its Olfactory Receptor Neurons (ORNs). Our understanding of the identity of specific progenitors or precursors that respond to these signals is, however, less well developed, and the search is still on for the elusive, definitive multipotent neuro-glial OE "Stem cell". Here, we review several lines of evidence that support the existence of a heterogeneous population of neural and glial progenitors in the olfactory mucosa, and highlight the differences in the identity and activity of progenitors found in the embryonic and adult OE. In particular, we show how recent advances in mouse transgenesis, and in the development of in vitro assays of progenitor activity, have helped to demonstrate the existence of multiple classes of olfactory mucosa-based progenitors. PMID- 17851772 TI - Rapid zygosity determination in mice by SYBR Green real-time genomic PCR of a crude DNA solution. AB - We examined whether crude DNA extracts prepared from gene-engineered mouse tissues are suitable as a template for zygosity determination by SYBR Green real time genomic PCR. A crude DNA solution was prepared by brief incubation with lysis buffer containing ear, tail, or fetus of ROSA26 mouse, a gene-trapped strain carrying the beta-galactosidase (beta-gal) gene. Five serially diluted crude DNA samples (original, 2-, 4-, 8-, 16-diluted) were next prepared and then subjected to three-step (95 degrees C, 60 degrees C and 72 degrees C) reactions of real-time PCR to detect the beta-gal gene and the receptor-activity-modifying protein 3 (ramp3) gene (as an internal reference gene). The slopes of standard curves obtained from the real-time PCR indicated that amplification efficiency was approximately 99%, and the efficiencies of target and reference were almost equal. With this system, we next determined the zygosity of mice derived from mating heterozygous ROSA26 females and males, and found a sharp distinction in zygosity, wild-type, heterozygous and homozygous. Assessment of crude DNA samples from other gene-engineered mice including B6ZP3Cre-Tg, B6rAM-Tg, and Ramp2-gene targeted strains revealed that our method was effective for determination of zygosity. The present method is more convenient and rapid than formerly published methods employing purified genomic DNA as a template. Our method will be particularly useful for experiments requiring rapid and accurate genotyping of gene-modified animals/fetuses. PMID- 17851773 TI - Cry3Bb1 protein from Bacillus thuringiensis in root exudates and biomass of transgenic corn does not persist in soil. AB - The Cry3Bb1 protein, insecticidal to the corn rootworm complex (Diabrotica spp.), of Bacillus thuringiensis (Bt) subsp. kumamotoensis was released in root exudates of transgenic Bt corn (event MON863) in sterile hydroponic culture (7.5 +/- 1.12 ng/ml after 28 days of growth) and in nonsterile soil throughout growth of the plants (2.2 +/- 0.62 ng/g after 63 days of growth). Kitchawan soil, which contains predominantly kaolinite (K) but not montmorillonite (M), was amended to 3 or 6% (vol./vol.) with K (3K and 6K soils) or M (3M and 6M soils) and with 1, 3, 5, or 10% (wt./wt.) of ground biomass of Bt corn expressing the Cry3Bb1 protein and incubated at 25 +/- 2 degrees C at the -33-kPa water tension for 60 days. Soils were analyzed for the presence of the protein every 7 to 10 days with a western blot assay (ImmunoStrip) and verified by ELISA. Persistence of the protein varied with the type and amount of clay mineral and the pH of the soils and increased as the concentration of K was increased but decreased as the concentration of M was increased. Persistence decreased when the pH of the K amended soils was increased from ca. 5 to ca. 7 with CaCO(3): the protein was not detected after 14 and 21 days in the pH-adjusted 3K and 6K soils, respectively, whereas it was detected after 40 days in the 3K and 6K soils not adjusted to pH 7. The protein was detected for only 21 days in the 3M soil and for 14 days in the 6M soil, which were not adjusted in pH. These results indicate that the Cry3Bb1 protein does not persist or accumulate in soil and is degraded rapidly. PMID- 17851774 TI - Development of an in planta method for transformation of alfalfa (Medicago sativa). AB - Conventional methods in transforming alfalfa (Medicago sativa) require multiple tissue culture manipulations that are time-consuming and expensive, while applicable only to a few highly regenerable genotypes. Here, we describe a simple in planta method that makes it possible to transform a commercial variety without employing selectable marker genes. Basically, young seedlings are cut at the apical node, cold-treated, and vigorously vortexed in an Agrobacterium suspension also containing sand. About 7% of treated seedlings produced progenies segregating for the T-DNA. The vortex-mediated seedling transformation method was applied to transform alfalfa with an all-native transfer DNA comprising a silencing construct for the caffeic acid o-methyltransferase (Comt) gene. Resulting intragenic plants accumulated reduced levels of the indigestible fiber component lignin that lowers forage quality. The absence of both selectable marker genes and other foreign genetic elements may expedite the governmental approval process for quality-enhanced alfalfa. PMID- 17851775 TI - Enhancing the carotenoid content of Brassica napus seeds by downregulating lycopene epsilon cyclase. AB - The accumulation of carotenoids in higher plants is regulated by the environment, tissue type and developmental stage. In Brassica napus leaves, beta-carotene and lutein were the main carotenoids present while petals primarily accumulated lutein and violaxanthin. Carotenoid accumulation in seeds was developmentally regulated with the highest levels detected at 35-40 days post anthesis. The carotenoid biosynthesis pathway branches after the formation of lycopene. One branch forms carotenoids with two beta rings such as beta-carotene, zeaxanthin and violaxanthin, while the other introduces both beta- and epsilon-rings in lycopene to form alpha-carotene and lutein. By reducing the expression of lycopene epsilon-cyclase (epsilon-CYC) using RNAi, we investigated altering carotenoid accumulation in seeds of B. napus. Transgenic seeds expressing this construct had increased levels of beta-carotene, zeaxanthin, violaxanthin and, unexpectedly, lutein. The higher total carotenoid content resulting from reduction of epsilon-CYC expression in seeds suggests that this gene is a rate limiting step in the carotenoid biosynthesis pathway. epsilon-CYC activity and carotenoid production may also be related to fatty acid biosynthesis in seeds as transgenic seeds showed an overall decrease in total fatty acid content and minor changes in the proportions of various fatty acids. PMID- 17851776 TI - The Chitinase A from the baculovirus AcMNPV enhances resistance to both fungi and herbivorous pests in tobacco. AB - Biotechnology has allowed the development of novel strategies to obtain plants that are more resistant to pests, fungal pathogens and other agents of biotic stress. The obvious advantages of having genotypes with multiple beneficial traits have recently fostered the development of gene pyramiding strategies, but less attention has been given to the study of genes that can increase resistance to different types of harmful organisms. Here we report that a recombinant Chitinase A protein of the Autographa californica nuclear polyhedrosis virus (AcMNPV) has both antifungal and insecticide properties in vitro. Transgenic tobacco plants expressing an active ChiA protein showed reduced damages caused by fungal pathogens and lepidopteran larvae, while did not have an effect on aphid populations. To our knowledge, this is the first report on the characterisation and expression in plants of a single gene that increases resistance against herbivorous pests and fungal pathogens and not affecting non-target insects. The implications and the potential of the ChiA gene for plant molecular breeding and biotechnology are discussed. PMID- 17851777 TI - Impact of single-gene and dual-gene Bt broccoli on the herbivore Pieris rapae (Lepidoptera: Pieridae) and its pupal endoparasitoid Pteromalus puparum (Hymenoptera: Pteromalidae). AB - Transgenic brassica crops producing insecticidal proteins from Bacillus thuringiensis (Bt) are being investigated as candidates for field release to control lepidopteran pests. Information on the potential impact of Bt brassica crops on pests and non-target natural enemies is needed as part of an environmental risk assessment prior to the commercial release. This first tier study provides insight into the tritrophic interactions among Bt broccoli plants, the herbivore Pieris rapae and its parasitoid Pteromalus puparum. We first evaluated the efficacy of three types of Bt broccoli plants, cry1Ac, cry1C and cry1Ac + cry1C, on different instars of P. rapae. Bt broccoli effectively controlled P. rapae larvae, although later instars were more tolerant. The efficacy of different Bt broccoli plants on P. rapae larvae was consistently cry1Ac > cry1Ac + cry1C > cry1C. When the parasitoid P. puparum developed in a P. rapae pupa (host) that had developed from Bt plant-fed older larvae, developmental time, total number and longevity of the P. puparum generated from the Bt plant-fed host were significantly affected compared with those generated from the non-Bt control plant-fed host. Simultaneously, negative effects on P. rapae pupae were found, i.e. pupal length, width and weight were significantly reduced after older P. rapae larvae fed on different Bt plants for 1 or 2 days. Cry1C toxin was detected using ELISA in P. rapae pupae after older larvae fed on cry1C broccoli. However, no Cry1C toxin was detected in newly emerged P. puparum adults developing in Bt-fed hosts. Only a trace amount of toxin was detected from entire P. puparum pupae dissected from the Bt plant-fed host. Moreover, no negative effect was found on the progeny of P. puparum developing from the Bt plant-fed host when subsequently supplied with a healthy host, P. rapae pupae. The reduced quality of the host appears to be the only reason for the observed deleterious effects on P. puparum. Our data suggest that the effects on P. puparum developing in Bt plant-fed P. rapae are mediated by host quality rather than by direct toxicity. PMID- 17851778 TI - Antibacterials as anti-inflammatory agents: dual action agents for oral health. AB - BACKGROUND: Inflammatory processes with a range of specialized cells and biochemical mediators form a complex network of inter-related signal transducing pathways that relay information to preserve normal functions. Advances in molecular analyses of the information relay pathways for their constituents and principal ligands along with mechanisms utilized by the host for microbial recognition have stimulated interest in therapeutic agents with dual functionalities i.e. antibacterial and anti-inflammatory effects. AIM: This review examines clinically tested agents for oral health applications with both antimicrobial and anti-inflammatory effects to include antibiotics, antimicrobials and phenolics. RESULTS: Bis-phenols such as triclosan, representing a unique dual functional therapeutic for routine oral hygiene, with its demonstrated clinical effects on inhibiting the dental plaque biofilm, reducing inflammation (gingivitis) and subsequent periodontitis is described. Cyclines, comprising another class of approved anti-inflammatory agents used at the patient level for oral health is discussed. Dual active agents in current clinical practice for systemic conditions are highlighted to summarize the clinical validity of dual function agents as an emerging therapeutic strategy. CONCLUSIONS: Clinical studies demonstrate therapeutic benefits of agents with dual functionality with their effects on microorganisms and the concomitant host inflammatory response. Advances in microbial pathogenesis and resultant inflammation will facilitate progress in this emerging area poised to be a significant milestone for dental therapeutics. PMID- 17851779 TI - Identification and preliminary analysis of a new PCP promoter from Brassica rapa ssp. chinensis. AB - The promoter of Brassica campestris Male Fertile 5 (BcMF5), a pollen coat protein member, class A (PCP-A) gene family, was isolated from Brassica rapa L. ssp. chinensis Makino (Chinese cabbage-pak-choi) by Thermal Asymmetric Interlaced Polymerase Chain Reaction (TAIL-PCR). Sequence analysis suggested that the 605-bp promoter of BcMF5 appears to be a pollen promoter. In an attempt to confirm the promoter activity of BcMF5 promoter, -609 to +3 bp and -377 to +3 bp fragments of the upstream sequence of BcMF5 were inserted at the site upstream of the coding region of the uidA gene in the sense orientation to construct two deletion expression vectors. Transient expression analysis in onion epidermal cells by particle bombardment showed that both -609 to +3 bp and -377 to +3 bp fragments of BcMF5 promoter were capable of driving beta-glucuronidase gene expression. Furthermore, by Agrobacterium-mediated genetic transformation method, Arabidopsis transgenic Kan(R) plants were obtained. GUS assay analysis revealed that the promoter of BcMF5 induced gene expression at the early stage of anther development and drove high levels of GUS expression in anther walls, upper regions of petals, pollen, and pollen tubes in the middle and late stage of anther development, but did not drive any expression in sepals and pistils. PMID- 17851780 TI - [Surgical treatment for patients with gastric cancer: report of 2335 cases]. AB - OBJECTIVE: To clarify the important factors affecting the prognosis of patient with gastric carcinoma. METHODS: The data of 2335 cases of resected gastric carcinoma from Jan. 1996 to Dec. 2005 were studied by using univariate analysis and multivariate regression analysis. RESULTS: Male patients accounted for 81.0% and female patients 19.0%. The ratio of male to female was 4.2: 1.0. Patients under 50 years old accounted for 77.2%. Two hundred and seventy-five cases were early gastric cancer, accounting for 11.8%, and another 2060 cases were advanced gastric cancer, accounting for 88.2%. Tumor diameter of 72.8% patients was more than 4 cm and 69.6% cases suffered with low differentiated cancer. Curative resections were performed in 1690 patients (72.4%) and palliative operation in other patients. After operation, 1538 cases (65.9%) received comprehensive treatment. For all cases, the 1-, 3- and 5-year survival rates were 71.9%, 45.3% and 40.1% respectively. The independent risk factors influencing prognosis of these patients were Borrmann classification,TNM staging, curative resection and multidisciplinary treatment through univariate and multivariate analyses. CONCLUSION: The factors influencing prognosis of patient with gastric carcinoma after resection are Borrmann classification,TNM staging, curative resection and multidisciplinary treatment. Early and curative resection is the most important management to improve therapeutic efficacy of stomach cancer. PMID- 17851781 TI - [Clinical values of extended lymph node dissection for gastric cancer:a meta analysis for D1 versus D2 gastrectomy]. AB - OBJECTIVE: To evaluate the survival, complication and postoperative mortality after D(1) or D(2) lymph node dissection for gastric cancer. METHODS: All the randomized clinical trials about nodal dissection for gastric cancer published within the last 20 years were collected. Quality assessment was done on each trial and relevant data were extracted from qualified trials. Meta-analysis was performed with the use of RevMan 4.2 (Cochrane) for statistic analysis. RESULTS: Three hundred and ninety-four trials were yielded at the initial search. Four trials, recruited 1316 cases of gastric cancer in total, were included after quality assessment. Results of Meta-analysis showed that standard D(2) dissection could effectively improve patients' long-term survival [RR 1.35, 95%CI(1.12 1.62), NNT=9] as compared with D(1) dissection. If splenectomy (or pancreatico splenectomy) was involved, D(2) dissection only improved the clinical outcome of T(3)-staged cases [RR 1.80,95%CI(1.03-3.15), NNT=13]. D(2) dissection produced higher rates of postoperative complication [RR 1.72,95%CI(1.46-2.03), NNT=6] and mortality [RR 2.12,95%CI(1.39-3.25), NNT=21] than D(1) dissection. CONCLUSIONS: Standard D(2) dissection can increase the overall survival rate when compared with D(1) dissection. If splenectomy (or pancreatico-splenectomy) cases are involved,D(2) dissection can only improve the survival rate of T(3)-staged patients. D(2) dissection yields higher postoperative morbidity and mortality than D(1) dissection. PMID- 17851782 TI - [Prognostic significance of metastatic lymph nodes ratio in patients with T2-T3 stage gastric cancer]. AB - OBJECTIVE: To evaluate the prognostic significance of metastatic lymph nodes ratio in patients with T(2)~T(3) stage gastric cancer. METHODS: Clinical data of 238 patients with T(2)-T(3) stage gastric cancer undergone radical gastrectomy and D(2) lymphadenectomy, at least 15 lymph nodes was dissected per patient, were analyzed retrospectively. Spearman correlation analysis was used to determine the correlation coefficient. Survival was determined by the Kaplan-Meier method and differences were assessed by the Log-rank test. Multivariate analysis was performed using the Cox proportional hazard regression model in forward stepwise regression. Receiver working characteristic curve was used to compare the accuracy of the metastatic lymph nodes ratio in predicting the death of patients 5 years postoperatively and that of metastatic lymph nodes number. RESULTS: The metastatic lymph nodes ratio didn't correlate with the total number of dissected lymph nodes, whereas metastatic lymph nodes number did. Kaplan-Meier survival analysis demonstrated the metastatic lymph nodes ratio significantly influenced the postoperative survival time and Cox proportional hazard regression model analysis showed the metastatic lymph nodes ratio was an independent poor prognostic factor. There was no significant difference between the area under the receiver working characteristic curve of metastatic lymph nodes ratio and metastatic lymph nodes number in predicting the death of patients 5 years postoperatively. CONCLUSIONS: The metastatic lymph nodes ratio in T(2)-T(3) stage gastric cancer patients is not correlated with the total number of dissected lymph nodes if at least 15 lymph nodes are dissected. The metastatic lymph nodes ratio is a major independent poor prognostic factor of the patients of T(2)-T(3) stage gastric cancer. The ability of the metastatic lymph nodes ratio in predicting the death of T(2)-T(3) stage gastric cancer patients 5 years postoperatively is the same as that of metastatic lymph nodes number. PMID- 17851783 TI - [Correlation analysis of gastric cancer with extranodal metastasis]. AB - OBJECTIVE: To evaluate the correlations between extranodal metastasis(EM)and clinicopathologic features of gastric cancer and the relationship between EM and prognosis of gastric cancer. METHODS: Data of patients with histologically proven adenocarcinoma were studied retrospectively to evaluate the prognostic factors in gastric cancer by univariate and multivariate analyses of Cox regression with SPSS 13.0 software. Two hundred and seventy-six patients with primary gastric cancer undergone operation in Tianjin Cancer Hospital from Jan. 2001 to Dec. 2001 were studied and followed up until Dec. 2006 or death. RESULTS: EMs were found in 58(21.0%) of the 276 patients. The overall 2-, 3-, and 5-year survival rates of the patients without EM were 71.2%, 55.4%, and 45.1% respectively. The overall 2 , 3-, and 5-year survival rates of the patients with EM were 24.1%, 15.5%, and 8.0% respectively. Postoperative overall survival rates were significantly lower for patients with EM than those without EM(P=0.000). EM was correlated with differentiation (r=0.163, P=0.008), invasive depth (r=0.215, P=0.003), lymph node metastasis (r=0.368, P=0.000), distant metastasis (r=0.375, P=0.000), advanced stage(r=0.441, P=0.000), and tumor size (r=0.167, P=0.007). Multivariate analysis identified EM as an independent prognostic factor. CONCLUSIONS: EM is correlated with many clinicopathological features of gastric cancer. EM is an independent prognostic factor of gastric cancer. PMID- 17851784 TI - [Rational approach to the management of IV stage gastric carcinoma with hepatic metastasis]. AB - OBJECTIVE: To investigate the benefit of surgical resection on the prognosis of patients with advanced gastric carcinoma and liver metastasis. METHODS: Data of 102 cases of advanced gastric carcinoma with liver metastases from 1993 to 2004 were studied retrospectively. RESULTS: The half-, one- and two-year postoperative survival rates of gastric carcinoma patients with H(1) metastasis undergone palliative resections were 69%, 44% and 6% respectively, which were significantly better than those of patients not undergone resection(accepted by-pass procedure or exploratory laparotomy) (P=0.009). The half-, one- and two-year postoperative survival rates of gastric carcinoma patients with H(2) metastasis undergone palliative resections were 56%,13% and 6% respectively, which were not significantly different compared with those of patients not undergone resection(P=0.068). The half-, one- and two-year postoperative survival rates of gastric carcinoma patients with H(3) metastasis undergone palliative resections were 25%, 13% and 0, which were not significantly different compared with those of cases not undergone resection (P=0.157). Regardless of peritoneal metastases, there were no significant differences between the survival rate of resection group and that of non-resection group. CONCLUSIONS: Gastric carcinoma patients with H(1) metastasis would benefit from palliative resection regardless of peritoneal metastasis. Gastric carcinoma patients with H(2) or H(3) metastasis are not benefit from surgical resection. PMID- 17851785 TI - [Clinical study of Ligasure versus conventional surgery for D2 lymphadenectomy of gastric cancer]. AB - OBJECTIVE: To examine the utility of the Ligasure vessel-sealing system in D(2) lymphadenectomy of gastric cancer, and compare with conventional hand tie method. METHODS: One hundred and twenty-four consecutive patients undergone D(2) lymphadenectomy of gastric cancer from Jan. to Oct. 2005 were enrolled in this study. Operations of 62 patients were performed with Ligasure, whereas the other 62 patients with hand tie method. Operative duration, volume of intraoperative hemorrhage and postoperative course were analyzed. RESULTS: There was significant difference in operative duration (187.3 min vs 210.5 min, P< 0.05) and no significant differences in volume of intraoperative hemorrhage, postoperative course, or duration of postoperative drainage between Ligasure group and conventional method group. No significant difference was observed in the frequency of postoperative complications between the two groups. CONCLUSION: D(2) lymphadenectomy of gastric cancer using Ligasure instead of conventional hand tie method appears to be technically feasible and easy. PMID- 17851786 TI - [Clinical value of routine haematoxylin-eosin stain in diagnosing submucosal lymphatic vessel infiltration in early gastric cancer]. AB - OBJECTIVE: To evaluate the value of routine haematoxylin-eosin(HE) stain for submucosal lymphatic vessel infiltration in early gastric cancer. METHODS: Four thousand four hundred and twenty early gastric cancer patients underwent D2 operation. Submucosal lymphatic vessel was detected by routine HE stain. The results were compared with pathological lymph node metastasis. RESULTS: In early gastric cancer, the sensitivity, specificity, accuracy, positive predicting value (PPV), and negative predicting value (NPV) of routine HE stain for submucosal lymphatic vessel infiltration were 54.5%, 82.0%, 78.9%, 27.4%, and 93.5% respectively. In early gastric cancer limited in mucosa, these indexes were 14.5%, 98.0%, 95.8%, 15.8%, and 97.8% respectively. In early gastric cancer infiltrated to submucosa, they were 60.3%, 57.8%, 58.3%, 28.1%, and 84.2% respectively. There were significant differences of submucosal lymphatic vessel infiltration with lymph node metastasis (P< 0.001), but no significant difference with survival rate. The 5-year survival rates of submucosal lymphatic vessel infiltration positive and negative group were 84.4% and 87.3%, median survival time was 6998 d and 7237 d, and mean survival time was 6163.9 d and 6042.6 d respectively (P=0.2495). CONCLUSION: The accuracy of routine HE stain is too low, thus it is not suitable for diagnosing submucosal lymphatic vessel infiltration in early gastric cancer. PMID- 17851787 TI - [Expression of ATP-binding cassette transporter ABCG2 in gastric carcinoma and its significance]. AB - OBJECTIVE: To investigate the expression of ATP-binding cassette transporter (ABCG2) in gastric carcinoma and its clinical significance. METHODS: Expression of ABCG2 protein was examined by immunohistochemical technique in specimens from 45 gastric carcinoma tissues and 30 surrounding normal tissues. The expression of ABCG2 mRNA was measured by RT-PCR and real-time quantitative PCR in specimens from 30 gastric carcinoma tissues and 30 surrounding normal gastric mucosa respectively. RESULTS: ABCG2 protein expression was observed in 28 of 45 (62.2%) cases by immunohistochemical analysis, while in 2 of 30 (6.7%) normal tissues (P< 0.05). In ABCG2-positive tumors, adjacent non-neoplastic tissue was similarly analyzed and revealed that ABCG2 was up-regulated in gastric carcinoma. The positive rates of ABCG2 expression in poorly differentiated and/or undifferentiated carcinoma were significantly higher than those in well and/or moderately-differentiated carcinoma (P< 0.05). The mRNA expression of ABCG2 was significantly higher in gastric carcinoma tissue than that in normal gastric mucosa (P< 0.05). CONCLUSIONS: ABCG2 expression is up-regulated in gastric carcinoma. ABCG2 may be an important factor in the research of gastric cancer stem cell. PMID- 17851788 TI - [Nuclear expression of S100A4 is associated with lymph node metastasis in gastric carcinoma]. AB - OBJECTIVE: To investigate the intracellular localization of S100A4 in gastric carcinoma cells and the relationship between S100A4 expression status and lymph node metastasis of gastric carcinoma. METHODS: Western blotting analysis was performed to locate the expression of S100A4 protein in sub-fraction components of frozen tissues. S100A4 protein expression was also determined by immunohistochemical method in 131 samples of gastric cancer and 20 samples of matched metastatic lymph nodes. RESULTS: Thirty-two of 131 (24.4%) gastric carcinoma showed positive S100A4 nuclear expression and 50/131 (38.2%) carcinoma showed positive cytoplasmic expression. In 32 samples with positive S100A4 nuclear expression, 30 (93.8%) carcinomas had positive lymph node metastases. S100A4 nuclear expression level was higher in gastric carcinoma with lymph node metastasis (29.1%) than that without lymph node metastasis (7.1%) (P=0.016). CONCLUSION: Nuclear expression of S100A4 is associated with lymph node metastasis of gastric carcinoma. PMID- 17851789 TI - [Expression and clinical significance of costimulatory molecule B7-H3 mRNA and B7 H3 protein in gastric carcinoma]. AB - OBJECTIVE: To study the expression of B7-H3 mRNA and B7-H3 protein in gastric carcinoma and their clinical significance. METHODS: The expression of B7-H3 mRNA and B7-H3 protein in gastric carcinoma and the nearby normal tissue of 38 patients was detected by real-time RT-PCR and immunohistochemical assay respectively. RESULTS: B7-H3 mRNA was expressed both in gastric carcinoma and nearby normal tissue, but the expression level in gastric carcinoma was much lower than that in nearby normal tissue. There were no significant differences of B7-H3 mRNA expression among gender, age, histological type, tumor size, lymph node metastasis and invasive depth (all P >0.05). The positive rate of B7-H3 protein expressed in gastric carcinoma was 39.5%. There were no significant differences of B7-H3 protein expression among gender, age, histological type, tumor size, lymph node metastasis and invasive depth (all P >0.05), but there were significant differences among groups of clinical stage (P=0.022) and pathological grade (P=0.039). Kaplan-Meier analysis revealed that disease-free survival or overall survival of the patients with positive B7-H3 expression were significantly longer than those with negative B7-H3 expression (P=0.009 and P=0.010 respectively). CONCLUSION: Detection of B7-H3 expression in gastric carcinoma will be beneficial to the judgment of the prognosis of gastric carcinoma and the choice of individualized treatment. PMID- 17851790 TI - [Effects of Tiam 1 antisense oligodeoxynucleotides transfection on the morphology and invasive migration potential of gastric cancer cells]. AB - OBJECTIVE: To investigate the effects of T lymphoma invasion and metastasis inducing factor 1 antisense oligodeoxynucleotides (Tiam 1 ASODN) transfection on the morphology and invasive migration potential of gastric cancer cells. METHODS: The higher invasive and migratory subgroup (M(H)) were separated from human gastric cancer cell line MKN-45 (M(0)) by laminin adhesion method in vitro. Tiam 1 ASODN was transfected into M(H) cells with liposome, and the expression of Tiam 1 mRNA and protein was determined by RT-PCR and flowcytometry respectively. The changes in morphology, the invasive and migratory potential between Tima 1 ASODN transfected M(H) cells and no transfected M(H) cells were observed by HE stain, cytoskeletal protein stain, scanning electronic microscope (SEM) and Boyden chamber test. RESULTS: Compared with the control, the expression of Tiam 1 mRNA and protein in M(H) cells was significantly decreased after transfected with 0.43 micromol/L ASODN(P< 0.01). The invasive and migratory potential of M(H) cells in vitro was also much more decreased than that of no transfected cells (P< 0.05 or P< 0.01). At the same time, transfected M(H) cells had less membrane surface projections, fewer or shorter pseudopodia, less irregular cytoskeletal network and less spotted-like actin bodys than no transfected M(H) cells did. CONCLUSION: Tiam 1 ASODN transfection can effectively suppress the expression of Tiam 1 in gastric cancer cells and impair its invasive and migratory potential in vitro, which may be fulfilled through modulating the reconstruction of cytoskeleton and decreasing the deforming and migratory potential of gastric cancer cells. PMID- 17851791 TI - [Effect of valproate acid sodium on apoptosis of human gastric cancer cells and its mechanism study]. AB - OBJECTIVE: To study the effect of valproate acid sodium(VPA) on apoptosis of human gastric cancer cell BGC-823 and to explore its possible mechanism. METHODS: Cell growth inhibition was examined by MTT assay. Apoptosis rate was detected by FCM with Annexin V/PI staining. The activities and protein expression levels of caspase 3, caspase 8 and caspase 9 were examined by spectrophotometry and indirect immunofluorescence technique respectively. RESULTS: The growth inhibition rate and apoptosis rate of human gastric cancer cells, treated with 0.75-4.00 mmol/L VPA for 24 h and 48 h, elevated in time- and dose-dependent manner. Apoptosis rates of VPA 0.75 mmol/L 24 h and 48 h were (7.2 +/- 0.5)% and (9.2 +/- 1.0)%, of VPA 4.00 mmol/L 24 h and 48 h were (16.7 +/- 2.2)% and (20.4 +/- 1.6)% respectively, which were significantly different as compared to the control [24 h, (4.9 +/- 0.2)%, 48 h, (5.1 +/- 0.8)%] (P< 0.001). The activities and protein expression levels of caspase 3 and caspase 9 were up-regulated compared with the control group (P< 0.001), meanwhile the activity and protein expression of caspase 8 enhanced slightly after VPA treatment for 48 h. CONCLUSION: VPA can inhibit the growth and induce the apoptosis of BGC-823 cells mainly through the activation of caspase 9 pathway. PMID- 17851792 TI - [Relationship of biological behavior and the prognosis in gastric carcinoid]. AB - OBJECTIVE: To examine the relationship of biologic behavior and prognosis in patients with gastric carcinoid. METHODS: A total of 26 gastric carcinoid patients proven by pathology from Jan. 1964 to Jan. 2005 were enrolled. All the patients survived after operations. Tumor size, invasion depth, regional lymph node metastasis, liver metastasis, adjuvant chemotherapy and 5-year survival were analyzed retrospectively. A univariate analysis of survival rate with respect to gastric wall infiltration, regional lymph node metastasis, liver metastasis, and adjuvant chemotherapy were accomplished by Kaplan-Meier estimation method. The Log-rank test was used to evaluate the level of significance. RESULTS: The average age of 26 patients was 58 years. Infiltration beyond the serosa occurred in 18 patients (69.2%), and regional lymph node metastases in 12 patients (46.2%). During the follow-up period, liver metastases occurred in 14 patients (53.8%). Tumor size was not associated with gastric serosa invasion, regional lymph node metastasis, liver metastasis and 5-year survival (P>0.05). Analysis of cumulative survival showed different survival time depending on gastric serosa invasion, regional lymph node metastasis and liver metastasis. The difference was significant (P< 0.05). In patients with gastric serosa invasion, regional lymph node metastasis and liver metastasis, estimated 5-year cumulative survivals were 16.7%, 16.7% and 0 respectively. Their prognosis was poor. Adjuvant chemotherapy was administrated in 10 patients (38.5%) and was not beneficial to prolong the survival time and increase the 5-year survival rate. The difference was not statistically significant (P>0.05). CONCLUSIONS: Surgical resection is the major strategy for the treatment of gastric carcinoid, and adjuvant chemotherapy is not proved to produce obvious effects. The prognosis of gastric carcinoid depends on the tumor infiltration of gastric wall, regional metastasis and liver metastasis. PMID- 17851793 TI - [Comparative study on clinical characteristics of gastric carcinoma between young and elderly patients]. AB - OBJECTIVE: To compare the clinical characteristics of gastric cancer between young and elderly patients,and bring forward corresponding countermeasures. METHODS: Clinical characteristics, treatment and prognosis between 79 young (or= 65 years old) patients were compared. RESULTS: The constituent ratio of gender between young and elderly group was not significantly different (P=0.226). There was no particularity of early symptom in young patients, but they had shorter course of disease (165 d vs 400 d, P=0.029) and more frequent inferior part of cancer (49.4% vs 41.7%, P=0.038) as compared to elderly patients. There was significant difference between two groups in pathological stage ratio (P=0.027). The median total survival time of young and elderly patients was 1006 d and 530 d respectively, which was not significantly different (P=0.108). Furthermore, median survival time of young and elderly patients after radical resection were 1197 d and 919 d respectively, and the difference was not significant as well (P=0.242). CONCLUSIONS: Characteristics of young patients with gastric cancer are lower incidence, larvaceous symptoms, more malignancy and quick development, which still remain general features of gastric cancer. By correct therapy, the efficacy of above young patients is similar to elderly patients. The key to improve prognosis is to further fortify cognition for gastric cancer and elevate early diagnostic rate. PMID- 17851794 TI - [Application of sandostatin in malignant bowel obstruction]. AB - OBJECTIVE: To investigate the effects of sandostatin in the treatment of malignant bowel obstruction(MBO). METHODS: The data of 51 patients with MBO from Aug. 1996 to June. 2004 were analyzed retrospectively. All the patients were divided into two groups: routine treatment group (n=19) and sandostatin combined with routine treatment group (n=32). Symptoms, gastrointestinal secretions, nasogastric tube(NGT) removing and effects of sandostatin on different obstructive location were observed. RESULTS: The symptom improvement in sandostatin group was 20/32 (63.1%) which was significantly higher than 4/19 (21.1%) in routine treatment group (P< 0.01). The average G-I secretion was (398 +/- 152) ml and (834 +/- 306) ml in sandostatin and traditional group respectively and the difference was significant (P< 0.05). No severe side and toxic effects were found during therapy. CONCLUSION: Sandostatin can effectively relieve clinical symptoms and improve life quality in the bowel obstruction cases with advanced cancers. PMID- 17851795 TI - [Study of the anti-tumor effect of anti-vascular endothelial growth factor McAb 5 fluorouracil loaded polylactic acid nanoparticles]. AB - OBJECTIVE: To explore the anti-tumor efficacy of anti- vascular endothelial growth factor (VEGF) McAb 5-fluorouracil (5-FU) loaded polylactic acid (PLA) nanoparticles (NPS) in human gastric carcinoma xenografts of nude mice. METHODS: Anti-VEGF McAb 5-FU loaded PLA NPS were made by ultrasound emulsification. Nude mice model of human gastric carcinoma xenografts was established. Therapeutic effects of drugs on human gastric carcinoma xenografts and side effects concerned were observed. RESULTS: The tumor inhibition rates of control group, nanosphere without 5-FU group, 5-FU (20 mg/kg) group, anti-VEGF McAb nanosphere without 5-FU group, anti-VEGF McAb group, nanosphere with 5-FU group, 5-FU (20 mg/kg) combined with anti-VEGF McAb group, anti-VEGF McAb 5-FU loaded nanosphere group was 0, 6.61%, 24.26%, 27.94%, 35.29%, 37.50%, 39.71% and 52.21% respectively, and there were no significant differences between anti-VEGF McAb 5-FU loaded nanosphere group and nanosphere group without 5-FU in WBC count, serum alanine transferase level or creatinine level. Compared with control group and anti-VEGF McAb 5-FU loaded nanosphere group, the 5-FU group decreased by 34.43% and 37.38% respectively in WBC count (P< 0.05), and increased by 93.17% and 66.56% respectively in alanine transferase. There were significant differences between experimental groups and control group in apoptosis index, especially between anti VEGF McAb 5-FU loaded nanosphere group and control group (P< 0.05). The microvessel density (MVD) of experimental groups containing anti-VEGF McAb was significantly lower than that of control group or groups containing 5-FU (P< 0.05). CONCLUSION: Anti-VEGF McAb 5-FU loaded nanosphere can increase the tumor inhibitory rate of 5-FU, induce apoptosis by inhibiting tumor angiogenesis with less side effect, and then enhance therapeutic effect, which indicate its potential as a novel, safe nano-tumor-targeting drug. PMID- 17851796 TI - Endogenous antioxidant defences in plasma and erythrocytes of pregnant women during different trimesters of pregnancy. AB - BACKGROUND: To assess the antioxidant capacity of pregnant women in Ogun State, Nigeria. METHODS: The activities of total superoxide dismutase (total SOD), manganese superoxide dismutase (Mn-SOD), catalase (CAT), glutathione transferase(GST), aminolevulinic acid dehydratase (ALAD), and the concentrations of glutathione (GSH), were determined in the plasma and red blood cells of non pregnant (n=20), normal healthy pregnant women during different trimesters of pregnancy (n=90), and pregnant women with pre-eclampsia (n=7). RESULTS: A 2-fold increase in erythrocyte CAT activity was observed in the pregnant women (p<0.05), while CAT activity in the pre-eclamptic women was not significantly different from control (p0.05). A 3-fold increase in plasma Mn-SOD was observed in the pregnant women including those with pre-eclampsia (p<0.05). ALAD activities in the first, second and third trimesters of pregnancy were 35, 51 and 55% of control, respectively (p<0.05), while in the women with pre-eclampsia it was 31% of control (p<0.05). Total SOD also decreased significantly in the erythrocytes of the pre-eclamptic women (p<0.05). Other antioxidants (GST and GSH) were not affected. CONCLUSIONS: Results suggest that oxidative stress is higher in pregnancy than in non-pregnant state. Our findings also suggest that while plasma Mn-SOD might play a significant role in detoxifying the superoxide anions produced in the placenta, the decomposition of hydrogen peroxide in erythrocytes is mainly due to CAT activity. Whether inhibition of ALAD contributes to the etiology of pre-eclampsia remains to be elucidated. PMID- 17851797 TI - Use of recombinant activated factor VII for massive postpartum hemorrhage. AB - OBJECTIVE: We hypothesised that patients with massive postpartum hemorrhage (PPH), defined as blood loss >1,500 ml,may benefit from the use of activated recombinant factor VII (rFVIIa). Design. Retrospective cohort study. Setting.Department of Obstetrics & Gynaecology, Dow University of Health Sciences. POPULATION: Thirty-four women with a diagnosis of massive PPH. METHODS: All patients with PPH who were admitted to the Department of Obstetrics &Gynecology and Surgical Intensive Care Unit of Civil Hospital Karachi, Pakistan, were included in the study. From March 2005 to October 2006, 34 patients fulfilled the criteria of massive PPH, of which 18 received rFVIIa to control bleeding, and 16 patients did not. Availability and cost of rFVIIa were the factors in drug allocation. Main outcome measures. Maternal mortality, correction of coagulopathy, the amount of blood products transfused and preservation of fertility. RESULTS: Patients receiving rFVIIa had lower maternal mortality (5/18, 28% versus 8/16, 50%, OR: 0.04 (0.002, 0.83)), and received a lower number of packed red cell transfusions (4.0 +/- 4.46 versus 9.61 +/- 6.7, p value 0.007), against the comparison group. Patients receiving rFVIIa had lower activated partial thromboplastin (median: 13.0; 25-75th percentile: -25.0, -8.0, signed rank p<0.0001), and lower prothrombin times (median: -8.8; 25-75th percentile: 24.2, -4.8), after administration of drug.There was no significant difference in the rate of hysterectomy between the 2 groups (11/18 (61%) versus 6/16 (38%)). No adverse event attributable to rFVIIa was observed in the study. CONCLUSION: Activated recombinant factor VII can be a lifesaving drug in patients with massive PPH. PMID- 17851798 TI - Cardiovascular and cortisol responses to a psychological stressor during pregnancy. AB - BACKGROUND: The goal of this study was to describe the physiological reactions of pregnant women confronted with an experimental psychosocial stressor, and to determine whether the protocol is adequate for stress testing during pregnancy. METHODS: Healthy primiparae (n=120) took part in a public speaking and mental arithmetic test. RESULTS: The protocol was found to induce significant increases in saliva cortisol, systolic and diastolic blood pressure and heart rate. The physiological reactions were relatively large compared to those of earlier published studies using physical and psychological stressors during pregnancy, but comparable or slightly lower than those of a group of non-pregnant participants (n=31) tested with a similar protocol. Also, inter-individual variability in reactivity was found, with subjects differing substantially in the magnitude of their reactions to the experimental situation. The cardiovascular responses were correlated to each other and to the overall level of cortisol during the test. Finally, reactivity showed circadian variations with cortisol and systolic blood pressure reactions significantly different (i.e. smaller or even absent) in subjects tested in the morning compared to those tested in the afternoon. Testing in the afternoon hours is recommended. CONCLUSIONS. The protocol described in this paper appears to constitute an adequate tool for studying differences in maternal stress reactivity during pregnancy, and as such,can be valuable for studies on maternal prenatal stress. PMID- 17851799 TI - Low predictive value of traditional risk factors in identifying women at risk for gestational diabetes. AB - BACKGROUND: There is no worldwide agreement on the best way to screen for gestational diabetes mellitus (GDM), and different diagnostic methods have been developed in order to identify women at risk. The aim of this study was to evaluate the prevalence and predictive value of the traditional risk indicators for GDM in a large group of Caucasian women. METHODS: We evaluated the frequency distribution of age, body mass index (BMI), prior macrosomia, prior GDM, and family history of diabetes of 1,414 pregnant women with GDM and 1,011 healthy pregnant women. RESULTS: The distribution of risk factors in both groups was different and significantly higher in GDM women. The cut-off value for age was 28 years, and 23 kg/m2 for BMI. The accumulation of two or more risk factors was frequent in GDM, but not in healthy women. By multiple logistic regression, there were significant interactions between independent variables of interest and GDM (OR: 3.19; p<0.001; sensitivity: 57.9%, specificity: 69.8%). The strongest predictors were prior GDM (OR: 4.35;95% CI: 2.42-7.82) and a family history of diabetes (OR: 3.03; 95% CI: 2.47-3.72); less predictive were age (OR: 1.69;95% CI: 1.44-1.99), BMI (OR: 1.50; 95% CI: 1.28-1.77), and prior macrosomia (OR: 1.64; 95% CI: 1.19-2.26). CONCLUSIONS: Selective screening based on traditional risk factors for GDM had relatively low sensitivity, and identified <60% of Caucasian women at risk. The cut-off value for BMI as a risk indicator (23 kg/m2) was lower than that proposed by guidelines about screening for GDM. PMID- 17851800 TI - Timing of induction of labour analgesia: what does an obstetrician need to know? PMID- 17851801 TI - Alterations in the 'local umbilical cord blood renin-angiotensin system' during pre-eclampsia. AB - BACKGROUND: Local autocrine-paracrine renin-angiotensin system (RAS), independently functioning from the circulating RAS, is present in major organs of the female reproductive tract. We have previously demonstrated 'a local RAS in human umbilical cord' via verifying the corresponding ACE, renin, and angiotensinogen mRNAs. The aim of this study is to search alterations of the local umbilical cord RAS during pre-eclampsia. METHODS: Cord blood samples were obtained from 19 patients with pre-eclampsia (aged mean 26.6 +/- 5.83 (range 18 42) years) and 20 women with normal pregnancy (aged mean 28.26 +/- 7.30 (range 19 37) years). Women with uncomplicated pregnancy formed the control group. Real time quantitative PCR analysis for ACE, renin and angiotensinogen gene expressions were carried out using a LightCyclerTM instrument. RESULTS: The mean expression ratios were 0.0029 +/- 0.0015 for renin, 0.153 +/- 0.166 for angiotensinogen, and 0.220 +/- 0.294 for ACE, in control samples. The mean expression ratios of pre-eclamptic patients were 0.0061 +/- 0.00068, 0.035 +/- 0.008, and 0.030 +/- 0.006 for renin, angiotensinogen and ACE genes, respectively. While renin expressions increased in the local cord blood of pre eclampsia in comparison to the normal cord blood, unpredictable decrements in the angiotensinogen and ACE expressions were observed within the same pre-eclamptic samples. There were no statistically significant differences between intrauterine growth restriction (IUGR) and appropriate for gestational age (AGA) newborns in respect to renin, angiotensinogen and ACE gene expressions. CONCLUSIONS: These findings indicate that the gene expression in the major components of the local RAS does not represent a constant mathematical model, but is affected from the ongoing pathobiological events associated with the disease course. Local umbilical cord blood RAS alterations at the basis of genetic expression are evident in pre-eclampsia. PMID- 17851802 TI - Lactose intolerance and long-standing pelvic pain after pregnancy: a case control study. AB - BACKGROUND: Long-standing pelvic pain during pregnancy and after delivery (PPP) is common. Its causes are not fully understood. A scientifically, undocumented, clinical observation is PPP patients often reporting unspecific abdominal pain and adverse reactions to milk. The main objective in this pilot study was to investigate if lactose intolerance, celiac disease or allergic propensity are risk factors for developing pelvic pain after delivery. METHODS: A matched, case control study,where consecutive patients consulting a registered physiotherapist specialised in treating women with postpartum pelvic pain were compared to matched controls. RESULTS: Lactose intolerance was found in 10 of 15 patients, and in 3 of 15 matched, healthy controls (p=0.05). No difference was seen between groups in the prevalence of celiac disease or allergic propensity. CONCLUSION: This study suggests that lactose intolerance might be a possible risk factor for pelvic pain after delivery. PMID- 17851803 TI - Completeness of registration of oral clefts in a medical birth registry: a population-based study. AB - BACKGROUND: Epidemiological surveillance and research on birth defects require accurate diagnosis and adequate registration. In this regard, the performance of national birth registries is not well described. METHODS: We linked clinical data from all 3,616 cleft cases treated in Norway between 1967 and 1998 with data from the Medical Birth Registry of Norway, and calculated the proportion of clinically verified cases reported to the Registry, stratified by severity. RESULTS: The cleft type most completely ascertained was cleft lip and palate (CLP), of which 94% were reported. Ascertainment was less complete for cleft lip alone (83% recorded), and cleft palate only (CPO) (57% recorded). For each of the three types of clefts, completeness of reporting depended on severity of the cleft. For example, 71% of cases with severe CPO were reported, while only 11% of cases with mild CPO were reported. CONCLUSIONS: Ascertainment was strongly related to cleft type and severity. To the degree that severity of birth defects may be related to their cause, these patterns of registration have implications for surveillance of birth defects as well as the conduct of etiologic studies. The large proportion of cleft palate cases unrecorded at birth suggests that clinical examination of the newborn palate is often inadequate. PMID- 17851804 TI - The effect of vaginal distension on the female urinary bladder and urethral sphincters. AB - AIMS: A mention of effect of vaginal distension, as induced by penile thrusting at coitus, on urinary bladder (UB) and urethral sphincters could not be traced in literature. We investigated the hypothesis that, upon vaginal distension, UB undergoes inhibited activity, while external and internal urethral sphincters (IUS) exhibit increased activity in order to guard against urine leakage during coitus. METHODS: Response of UB and external and IUS to vaginal balloon distension was recorded in 28 healthy women (age 35.6+/-3.3 years). A vaginal condom was inflated with air in increments of 50 up to 200 ml, and vesical pressure as well as electromyographic (EMG) activity of external and IUS were registered. The test was repeated after separate anaesthetisation of vagina, UB and external and IUS. RESULTS: On vaginal distension, vesical pressure was reduced in the ratio of expansion of vaginal volume up to a certain capacity, beyond which vesical pressure ceased to decline when distending volume was augmented. Similarly, IUS EMG activity increased progressively on incrementally added vaginal distension up to 150-ml distension, beyond which any further vaginal distension did not produce an additional increase of EMG activity; the external urethral sphincter (EUS) EMG activity showed no response. Vaginal distension, while the vagina, UB and external and IUS had been separately anaesthetised, produced no significant change. CONCLUSION: Vaginal balloon distension seems to effect vesical wall relaxation and increase IUS tone. This appears to provide a mechanism that prevents urine leak during coitus. Vesical and IUS response to vaginal distension are suggested to be mediated through a reflex we term 'vagino-vesicosphincteric reflex', which seems to be evoked by vaginal distension during penile thrusting. The reflex may prove of diagnostic significance in sexual disorders. PMID- 17851805 TI - Leisure time physical activity during pregnancy and impact on gestational diabetes mellitus, pre-eclampsia, preterm delivery and birth weight: a review. AB - BACKGROUND: It has been questioned whether leisure time physical activity (LTPA) during pregnancy is beneficial or deleterious to pregnancy outcome, and whether a sedentary lifestyle during pregnancy has a negative impact on pregnancy. Answers to these questions are of general interest, since some young women are very physically active during leisure time, while others have a sedentary lifestyle. METHOD: In this review, we analysed the association between LTPA and the selected pregnancy outcomes, gestational diabetes mellitus (GDM), pre-eclampsia, preterm delivery, and birth weight. RESULTS: The prevailing literature clearly indicates that LTPA before and/or during pregnancy has a protective effect on the development of GDM and pre-eclampsia. Furthermore, LTPA does not seem to have a negative impact on the rate of preterm delivery or on birth weight. CONCLUSION: Thus, it seems relevant that health authorities recommend 30 min of daily physical activity to healthy pregnant women. PMID- 17851806 TI - Laparoscopic laser resection of rectovaginal pouch and rectovaginal septum endometriosis: the impact on pelvic pain and quality of life. AB - BACKGROUND: The aim of this study was to assess the impact on pelvic pain and quality of life of laparoscopic resection of the rectovaginal pouch (RV) and RV septum in patients with endometriosis. METHODS: The design was a descriptive retrospective study. The study included 48 women presenting to the Department of Obstetrics and Gynaecology with RV pouch and RV septum endometriosis, between 1 January 2003 and 1 January 2006. The setting was a university teaching hospital, one of two referral centres in Denmark for the surgical treatment of stage III and IV endometriosis. Questionnaires and Visual Analogue Scale (VAS) scores for a number of different symptoms associated with endometriosis were used. The main outcome measures were: effect of laparoscopic excision on pain scores and quality of life, operative findings, type of surgery, duration of surgery, and incidence of intra- and postoperative complications. RESULTS: Significant statistical differences were found between preoperative and postoperative pain scores, quality of life, frequency of sexual activity, percentage taking analgesics or non-steroidal anti-inflammatory drugs, percentage having work difficulties due to pain, and percentage of women having sick-leave. CONCLUSION: Endometriosis in the RV pouch and RV septum can be effectively treated with laser laparoscopy performed by experienced endoscopic gynaecologists. PMID- 17851807 TI - Fetal gender screening by ultrasound at 11 to 13(+6) weeks. AB - BACKGROUND: To survey the accuracy of fetal gender determination during first trimester screening and scan for congenital anomalies. METHODS: A prospective observational study was performed on 496 singleton pregnancies at the first trimester ultrasound screening. The doctor was a certified sonographer of first trimester screening by the Fetal Medicine Foundation(FMF). Ultrasound examination was performed on a GE Voluson 730 Pro, transabdominally, between 11 and 13(+6) weeks. Both transverse and mid-sagittal planes of a section of the fetal genital tubercle were performed to identify the gender. The subsequent gender at birth was obtained from karyotyping reports or hospital birth records. RESULTS: During the study, 496 patients requested gender information at the time of first trimester screening. Of the patients it was possible to determine gender (441 out of 496), the scan achieved an overall success rate of 91.8% in correctly identifying gender. The success rate for correctly identifying fetal gender (where identification was possible) increased with gestational age, from 71.9% at 11 weeks, 92% at 12 weeks, and 98.3% at 13 weeks, respectively, where gestational age was calculated from the crown-rump length in conjunction with menstrual or ovulation dating (p<0.001). Of the 55 cases where no identification of gender was possible, 39 were in the 11-week gestational age group, representing 40.6% of this category. The overall fetal gender accuracy rate for male fetus was slightly better than female (92.5 versus 91.2%), but was not statistically significant. CONCLUSIONS: This study demonstrated that the gestational age of the fetus has a material effect on the accuracy rate of gender determination. At 12 weeks and over, the average success rate for correctly identifying gender, where gender identification was possible, was 94.8%, with the accuracy at 13 weeks of 98.3% approaching that achieved by invasive testing. Fetal gender identification at 11 PMID- 17851808 TI - Characteristics and outcome of fetal cystic hygroma diagnosed in the first trimester. AB - OBJECTIVE: The aim of this study was to determine the course of pregnancy and the neonatal outcome of fetuses with cystic hygroma diagnosed at 10-14 weeks' gestation. METHODS: Maternal and fetal data (nuchal translucency, karyotype, pregnancy outcome) in cases of fetal cystic hygroma, admitted or referred to our antenatal diagnostic centre, were prospectively entered into a computer database. Paediatric outcome was analysed when relevant. RESULTS: Some 72 fetuses had cystic hygroma. The mean size of the cystic hygroma was 7.9 mm. Chromosomal abnormalities were present in 52.7% of cases (38/72), including 14 cases (36.8%) of Down syndrome. A total of 34 chromosomally normal pregnancies gave rise to 18 live births (52.9%), with no visible serious structural abnormalities. The outcome of pregnancy was unfavourable (miscarriage, elective termination, serious structural abnormalities) in 77.7% of cases (56/72). The 18 live-born infants were followed up for 17-98 months. Sixteen infants developed normally, while 1 developed Noonan's syndrome and 1 had a urinary tract abnormality (pyelo-ureteral junction; PUJ). CONCLUSION: These data suggest that the prognosis of fetal cystic hygroma detected during the first trimester is poor, and show that sonographic evaluation of fetal nuchal translucency thickness in the first trimester is crucial. PMID- 17851809 TI - The application of 'endovaginal' sonography during a laparoscopy-assisted Vecchietti operation. AB - BACKGROUND: Many types of operations are described to create a neovagina in a patient with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, that sometimes result in injury of the surrounding organs. Many trials are detailed in the literature to avoid these complications. Our goal was to examine the benefit of 'endovaginal' sonography during a laparoscopy-assisted Vecchietti operation to avoid bladder injuries. METHODS: A neovagina was created in 15 women with MRKH syndrome by the method of Vecchietti assisted by laparoscopy. The method was modified with the use of'endovaginal' sonography, in order to reduce bladder and rectal injuries. The vaginal ultrasound transducer, placed in front of the vaginal dimple, can guide penetration from the perineum into the peritoneal cavity. With this technique, the narrow space between the bladder and rectum can be well identified. RESULTS: All operations were successful, without any complication, forming a well-functioning 8-10 cm long neovagina, allowing easy introduction of two fingers in all cases, and with good quality of sexual life for the couples. CONCLUSION: Creation of a neovagina by any method in MRKH syndrome may sometimes result in injury of the bladder or rectum due to the narrow space between the bladder and rectum. The placement of the endovaginal ultrasound transducer in front of the vaginal dimple seems to be a promising method to avoid these complications during a laparoscopy-assisted Vecchietti operation. PMID- 17851810 TI - FDG-PET in cervical cancer: staging, re-staging and follow-up. AB - BACKGROUND: Correctly visualising the extent of the disease in cervical cancer is difficult with today's conventional imaging modalities. This paper presents the interim analysis of an on-going prospective study to evaluate the potential role of FDG-PET with software fusion with CT images in 3 different clinical settings of cervical cancer. METHODS: In Group 1, 10 patients with early stage cervical cancer underwent FDG-PET 6 months after surgery. Group 2 consisted of 17 patients with locally advanced cervical cancer who underwent FDG-PET as part of the staging procedure. In Group 3, 12 patients with verified relapse and 3 patients with a strong suspicion thereof underwent FDG-PET before starting any therapy. The FDG-PET results were compared with the results of the standard conventional work-up. All patients had a follow-up time of at least 6 months. RESULTS: All FDG PET scans in Group 1 were true negative. In Group 2, FDG-PET detected previously unknown locations of metastases in 4 patients, and a synchronous pulmonary carcinoma in 1 patient, resulting in a change in treatment plan for 4 patients. One false negative FDG-PET result was recorded. In Group 3, FDG-PET results led to a change in treatment plan for 3 patients. CONCLUSIONS: We conclude that FDG PET provides crucial information in the pre-treatment staging procedure in patients with locally advanced or relapsed cervical cancer. However, in the follow-up of early cervix cancer, FDG-PET 6 months post-operatively offered no clinical benefit in this small group of patients. PMID- 17851811 TI - Attitudes towards and management of single embryo transfer among Nordic IVF doctors. AB - BACKGROUND: The objective of this study was to investigate the attitudes towards and management of single embryo transfer(SET) among Nordic in vitro fertilisation (IVF) doctors, and to present the rate of SET and multiple pregnancies in the different countries. METHODS: A questionnaire was sent to all IVF doctors in the Nordic countries (n=198, 78.5% responded). Pregnancy rates, SET and multiple births rates were extracted from registries. Main outcome measure was attitudes and management of SET. RESULTS: Almost all doctors thought that a twin pregnancy compared unfavourably to a singleton. A twin rate >10% was acceptable for 5% of Swedish doctors. Corresponding figures for Finnish, Danish and Norwegian doctors were 21, 35 and 35%, respectively. For a woman <36 years, performing her first cycle and with two good quality embryos, almost all doctors would recommend SET. For a woman >= 36 years in a similar situation, SET would be recommended only in Sweden and Finland. The pregnancy rate per embryo transfer (ET), the SET rate 2003, the multiple birth rate, and the estimated SET rate 2004 were 33.3, 21.5, 22.7 and 25% (Denmark), 31.3, 43.4, 14 and 51%(Finland), 40.5, 10.5, 26.5 and 16% (Iceland), 30.6, 18, 25.2 and 26% (Norway), and 35.3, 55.1, 11.8 and 71% (Sweden). CONCLUSIONS: The SET and multiple birth rates reflect the attitudes of Nordic IVF doctors to SET and multiple births well.When introducing SET, the attitude of the IVF doctor seems to be important. PMID- 17851812 TI - Reliability of an automatic ultrasound system for detecting postpartum urinary retention after vaginal birth. AB - BACKGROUND: Urinary retention is a common postpartum condition which may lead to short- and long-term complications.Objective. To assess the reliability of a commercially available automatic bladder volume scanner in the puerperium, and to specifically identify women with a post-void residual volume of 400 ml or more. METHODS: A prospective comparison of ultrasound estimated bladder volume and urine volume measurement after catheterisation in 100 women at risk for postpartum urinary retention (PUR) after vaginal delivery. RESULTS: The mean difference between the ultrasound estimates and the catheter volume measurements was 26 ml, with the corresponding 95% confidence interval (2.6, 49.4 ml). The sensitivity and specificity for the scanner, using the clinically desired value of a 400-ml threshold, are 0.76 and 0.96,respectively. With a perfect classification for sensitivity at a 300-ml threshold, specificity may drop to about 50%. Even using this cut-off point, the number of women catheterised would be reduced by half compared to a procedure of catheterising all women at risk for postpartum urine retention diagnosed by clinical judgment alone. CONCLUSION: The ultrasound scanner is a reliable screening instrument for detecting PUR after vaginal birth. PMID- 17851813 TI - Does childbirth after fertility treatment influence sense of coherence? A longitudinal study of 1,934 men and women. AB - BACKGROUND: Infertility is a severe, stressful experience. Sense of coherence (SOC) is an individual attribute which reflects the ability to resist severe strain. According to Antonovsky, SOC is stable throughout adulthood, but there is little empirical evidence to support this. In a prospective study, we focused on 2 research questions: (i) Does childbirth after assisted reproductive technology (ART) result in high SOC? (ii) Does the level of SOC at baseline influence the association between childbirth after ART and SOC at 1-year follow-up? METHODS: The study included a consecutive sample of patients in ART from a prospective, longitudinal survey in Denmark; baseline response rate 80.0%, 1-year follow-up 87.7% (n=1,934). The dependent variable was SOC at 1-year follow-up measured by Setterlind's 9-item scale. The independent variable was having achieved childbirth after ART. Data were analysed by logistic regression analysis adjusted for baseline SOC. RESULTS: Having achieved childbirth after ART was associated with higher SOC at 1-year follow-up (women OR=1.81,95% CI: 1.202.74; men OR=1.27, 95% CI: 0.881 - 86). Unexpectedly, the association between achieving childbirth after ART and high SOC at 1-year follow-up was significant among women who had low SOC at baseline. There was no association among participants with high SOC at baseline. CONCLUSIONS: The study indicated that SOC is not necessarily stable throughout adulthood, since a successful outcome of ART among women was associated with a significant increase in SOC. PMID- 17851814 TI - Diabetes and urinary incontinence - prevalence data from Norway. AB - BACKGROUND: Few large epidemiological studies have investigated whether diabetes might increase the risk for, or cause greater severity of, urinary incontinence. The aim of the present study was to investigate the association between diabetes and urinary incontinence, including the possible influence of diabetes on the severity of incontinence. METHODS: The study was a cross-sectional, population based, study from the county of Nord-Trondelag, Norway, from 1995 to 1997. Data were collected by means of questionnaires, simple clinical measurements, and some blood tests. A total of 21,057 women, 20 years or older, answered the questions on both diabetes and incontinence, and 685 women were identified with diabetes. RESULTS: The prevalence of incontinence among women with diabetes was 39% compared to 26% in women without diabetes. The women with diabetes had more urge and mixed incontinence. The associations between diabetes and urge incontinence (OR: 1.49; 95% CI: 1.03-2.16), mixed incontinence (OR: 1.32; 95% CI: 1.05-1.67), and severe incontinence (OR: 1.54; 95% CI: 1.21-1.96) were still significant after adjusting for age, body mass index, parity and smoking. CONCLUSION: We found a strong association between diabetes and urinary incontinence, especially for urge incontinence and severe degree of incontinence. PMID- 17851815 TI - Is operative delivery associated with postnatal back pain at eight weeks and eight months? A cohort study. AB - BACKGROUND: Back pain is very common during pregnancy and postnatally, and is a serious cause of morbidity. This research investigates the prevalence of antenatal back pain and the associations between mode of delivery and postnatal back pain at 8 weeks and 8 months. METHODS: A prospective population-based cohort based in Avon, UK. Some 14,663 women were recruited antenatally, due between 1 April 1991 and 31 December 1992. Of these, 12,944 women with singleton, liveborn, term fetuses were included. Self-reported postal questionnaires were used to assess back pain antenatally and postnatally. The main outcome measures were postnatal back pain at 8 weeks and 8 months. RESULTS: Back pain was very common with a prevalence of 80% at 32 weeks antenatally. Postnatally, back pain affected 68% of women at 8 weeks, and 60% at 8 months. Postnatal back pain was not associated with elective or emergency caesarean section (e.g. adjusted 8 weeks OR: 1.23, 95% CI: 0.89, 1.70, and OR: 0.89, 95% CI: 0.65, 1.22, respectively) nor with assisted versus spontaneous vaginal delivery (OR: 0.99, 95% CI: 0.82, 1.20). Very similar patterns were observed at 8 months. CONCLUSIONS: Antenatal and postnatal back pain are common. Elective caesarean section does not protect against postnatal back pain. Neither emergency caesarean section nor assisted vaginal delivery increases the risk of postnatal back pain compared with spontaneous delivery. PMID- 17851816 TI - Use of insulin glargine during pregnancy. AB - BACKGROUND: Good metabolic control maintained throughout pregnancy reduces maternal and fetal complications in diabetic women. The long-acting insulin analogue glargine has 24-h persistence and a peakless action profile, and could contribute to more stable daily plasma glucose levels and improved glycemic control. We evaluated the metabolic control associated with insulin glargine during pregnancy in comparison with conventional basal insulin therapy. METHODS: Retrospective case-control analysis of glycemic control and pregnancy complications in 100 type 1 diabetic pregnancies with intermediate-acting NPH insulin or insulin glargine prior to conception and throughout pregnancy. RESULTS: Overall,glycemic control was not different between the groups, though the decrease in HbA1c from the first to the third trimester was greater with insulin glargine (0.8 versus 0.3%, p=0.04). The rate of hypoglycemia was comparable. CONCLUSIONS: Our findings suggest that, as regards metabolic control, insulin glargine in women with type 1 diabetes is comparable with NPH insulin as basal insulin therapy. No adverse effects were associated with glargine use at the time of conception and during pregnancy. PMID- 17851817 TI - Postmenopausal endometriosis. AB - BACKGROUND: Postmenopausal endometriosis is rare. The purpose of this presentation is to give a review of the topic based on existing literature. METHODS: A Medline search concerning postmenopausal endometriosis was carried out. Hormone therapy and risk of malignancy in these patients are discussed. RESULTS: Some 32 case reports on postmenopausal endometriosis were found. The most common location is in the ovaries. Estrogens stimulate endometriosis. There is a risk of recurrence or de novo occurrence of endometriosis after the menopause in patients who take hormone therapy (HT); especially estrogen only therapy (ET). So far, treatment has primarily been surgery (hysterectomy (TAH) and bilateral oophorectomy (BSO)).There is little experience with medical treatment (aromatase inhibitors). The risk of malignant transformation of premenopausal endometriosis is around 1%. Furthermore, patients with endometriosis have an increased risk of ovarian cancer, and, apparently, other malignancies. The risk of malignant transformation appears to be further elevated in patients who take ET, although this subject is not fully elucidated. CONCLUSIONS: Although the condition is rare, it is important to be aware of endometriosis after the menopause. Postmenopausal endometriosis infers a risk of recurrence and malignant transformation. Although solid evidence is lacking, the risk of malignant transformation appears to be lower during combined HT compared to ET. Thus, hormone replacement therapy should generally be reserved for patients with severe climacteric complaints, and if indicated, combined therapy should be used. PMID- 17851818 TI - Organisation and quality of primary surgical intervention for ovarian cancer in Denmark. AB - BACKGROUND: The positive effect on survival of maximal primary cytoreductive surgery for ovarian cancer is well established, and the highest rates of optimal cytoreduction are achieved by gynecological oncologists. Danish women have not only one of the highest incidences of ovarian cancer, but also the highest mortality rate. From 1981 to 1989, the overall Danish optimal debulking rate was 25% in patients with stage III and IV tumors. The primary aim of the present study was, therefore, to evaluate the organisation and quality of current primary surgical intervention for ovarian cancer in Denmark. METHODS: All women diagnosed with epithelial ovarian carcinoma (DC56) were identified through the Danish National Patient Registry during the study period from 1 July 2002 to 31 December 2003, and surgical notes and histopathology were evaluated by a board of 7 gynecological-oncologists, focusing on maximal cytoreduction. RESULTS: For stage III, the nationwide optimal debulking rate was 39%, significantly higher in the major hospitals (49%) versus other hospitals (29%) (p<0.005). In 19% of cases, there was insufficient information to evaluate debulking from the surgical notes, significantly less at the major hospitals versus other hospitals (12 versus 25%, p<0.001). CONCLUSIONS: In Denmark, the quality of the primary surgical intervention for ovarian cancer is not optimal. In order to enhance survival, compliance with international guidelines and improved registration of the surgical procedures in clinical databases are mandatory. PMID- 17851819 TI - Maternal anxiety about first trimester nuchal translucency screening and impact of positive screening results. AB - BACKGROUND: To assess pre- and post-procedural maternal anxiety about nuchal translucency thickness screening for Down syndrome in the first trimester of pregnancy, and the psychological impact of positive screening results. METHODS: A total of 172 women whose screens were positive for excess fetal nuchal translucency thickness, and 180 women whose screens were within normal limits (controls) were recruited. Anxiety levels were measured with the Spielberger State-Trait Anxiety Inventory just before screening, 1 week after screening, at 22 weeks' gestation, and 6 weeks after delivery. After delivery, all women were asked to respond using a Likert-type scale regarding their attitudes toward fetal nuchal translucency screening. RESULTS: Women with positive screening results reported significantly greater psychological distress on state-anxiety scores after the full report was received. The trait- and state-anxiety scores before screening, at 22 weeks' gestation, and after delivery did not differ between groups. Both groups of women were strongly positive about nuchal translucency screening, both in the current pregnancy and in future pregnancies. CONCLUSION: Women with positive screening results did not have a sustained increase in anxiety and remained supportive about the value of screening. Clinician concerns about causing maternal anxiety should not be an impediment to screening. PMID- 17851820 TI - Preferences for involvement in treatment decision-making among Norwegian women with urinary incontinence. AB - BACKGROUND: Current health policies advocate patient participation in treatment decision-making. Objective. To explore whether role preferences among women with urinary incontinence (UI) change depending on the treatment decision-making context. We also explore what factors are associated with role preferences and changes in role preferences. METHODS: A national telephone survey of 265 women with UI identified from 1,000 randomly selected Norwegian women aged 18 or over. The interview included questions on socioeconomic factors, general health status, UI-related factors, and role preferences. Women were categorised as preferring an 'active', 'collaborative', or 'passive' role in treatment decision-making based on their selection of a response from the Control Preferences Scale. RESULTS: Women's preferences changed significantly when considering UI treatment decision making compared to treatment decision-making generally (p<0.001). A total of 60% preferred an active role in UI treatment decisions compared to 38% when considering treatment decision-making generally. Multivariable analyses found that higher education was significantly associated with preferring an active role in general treatment decision-making. For UI treatment decision-making, women aged 60 or over and those who were married or had a partner were less likely to prefer an active compared to a collaborative role. CONCLUSIONS: Women with UI prefer a more active role when considering UI treatment decision-making compared to treatment decision-making generally. Factors associated with role preferences vary depending on the decision-making context, with older women and those who were married or had a partner less [corrected] likely to prefer an active role when considering UI treatment decision-making. PMID- 17851821 TI - Sulforaphane induces growth arrest and apoptosis in human ovarian cancer cells. AB - OBJECTIVES: Isothiocyanates (ITC) from broccoli and other cruciferous vegetables have long been shown to have chemopreventive properties, as demonstrated in cancer models in rodents. Sulforaphane (SFN) is a major ITC present in broccoli. We examined the effects of SFN on the growth of the OVCAR-3 and SKOV-3 ovarian carcinoma cell lines. METHODS: Cell cycle phase determination was performed using a Coulter flow cytometer. DNA strand breaks in apoptotic cells were measured by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labelling (TUNEL). RESULTS: There was a concentration dependent decrease in cell density. Approximately 50% decrease was observed after 48 h of incubation with SFN (2 MUM). Analysis of cell cycle phase progression revealed a decrease in the cell populations in S and G2M phases, with an increase of G1 cell population, indicating a G1 cell cycle arrest. The degree of decrease in the replicating population was concentration and time dependent. Incubation of OVCAR-3 cells in cultures with concentrations of 2, 10 and 50 MUM of SFN showed 6, 8 and 17% apoptosis, respectively. In addition, when OVCAR-3 cells were exposed to SFN for various time periods (1, 2 or 3 days), the percentage of cells undergoing apoptosis was directly proportional to the incubation period. In this regard, while 18% of the cells underwent apoptosis after 2 days, 42% of the cells showed apoptosis after 3 days of incubation. CONCLUSIONS: These results clearly demonstrated an effect of SFN in inducing growth arrest and apoptosis in ovarian carcinoma cell lines. PMID- 17851822 TI - Surgical repair of posterior compartment prolapse: preliminary results of a novel transvaginal procedure using a four-armed polypropylene mesh with infracoccygeal and pararectal suspension. AB - BACKGROUND: Anatomical defects of the posterior vaginal compartment are a common reason for pelvic floor reconstructive surgery. The implantation of a four-armed monofilamentous polypropylene mesh with infracoccygeal and pararectal suspension is a recently introduced innovative technique, which is believed to reduce the risk of mesh retraction and prolapse recurrences, and additionally, allows a tension-free adjustment of the mesh. METHODS: In this preliminary case series, we aimed to evaluate feasibility, intraoperative complications and short-term follow up results of this novel surgical procedure in a multicentre approach. Seventy three patients undergoing surgery for posterior vaginal compartment prolapse were enrolled. The mean follow-up time was 3.8 months (range: 2-6 months), and follow up information was available in 60/73 (82.2%) women. RESULTS: Intraoperative complications were observed in 4.2% of cases, 2 patients with blood loss >500 ml, and one bladder injury occurring during concomitant anterior compartment surgery. Importantly, there were no intraoperative complications directly related to the implantation technique (e.g. rectum perforations), and no prolapse recurrences at follow-up examinations 3-6 months postoperatively. Our short-term mesh erosion rate was 3.1%. CONCLUSIONS: We conclude that this innovative procedure is a feasible and safe technique for the treatment of posterior vaginal compartment prolapse. Further prospective and multicentre trials are warranted. PMID- 17851823 TI - Correlations between unsatisfactory colposcopy, cytology, and biopsy in patients with cervical abnormalities. AB - BACKGROUND: The main purpose of this study is to review the clinical features of negative loop electrosurgical procedure(LEEP)-cones, in order to lower their rate. METHODS: Some 162 patients with LEEP-cones were reviewed. Control cytology,satisfactory-unsatisfactory colposcopy, biopsies and endocervical curettage (ECC) were compared to the presence or absence of cone pathology. Statistical analysis, t -tests and Pearson x2 tests were performed, with a significance level of p<0.05. RESULTS: Negative cones are associated with unsatisfactory colposcopy in 47/60 cases (78.3%) compared to 13/60(21.8%) for satisfactory colposcopy (p=0.011). Unsatisfactory colposcopy is associated with a negative ECC in 53/74(71.6%) cases, compared to 21/74 (28.4%) for satisfactory colposcopy (p=0.024). Finally, negative ECC are associated with negative cones in 32/41 (78%) compared to 9/41 (22%) for positive ECC (p=0.002). CONCLUSIONS: Low grade cytology, CIN1 biopsies and ECC should be followed for at least 1 year. This results in a lowering of cone negativity from 60/162(37%) to 32/162 (19.8%). PMID- 17851824 TI - Prevalence of polyhydramnios at a Danish hospital--a population-based study. AB - BACKGROUND: The purpose of this study was to determine the incidence of polyhydramnios, the related maternal and perinatal morbidity, and to estimate the association between perinatal outcome and the degree of polyhydramnios in a Danish population. METHODS: The study population consisted of 168 women with singleton pregnancies and polyhydramnios diagnosed by ultrasound as a largest two diameter pocket of > 50 cm2. Mild polyhydramnios defined as > 50 and < 100 cm2, and severe polyhydramnios defined as > or = 100 cm2. The background population consisted of 8,347 pregnant women from the same hospital. Outcome measures were compared using chi2 test or Fisher's exact test. RESULTS: The incidence of polyhydramnios was 2%, with 66.7% of cases mild, and 33.3% were severe polyhydramnios. The study population had an increased risk of emergency (19 versus 10.5%, p<0.001) and elective (11.3 versus 5.0%, p<0.001) caesarean section, as well as perinatal death (1.2 versus 0.3%, p<0.05) compared to the background population. In cases of severe polyhydramnios, there was an increased risk of caesarean section (44.6 versus 23.1%, p<0.005), birth weight > 4,000 g (28.6 versus 14.3%, p<0.05), and need for neonatal care (8.9 versus 0.9%, p<0.01) compared to mild cases. Apgar score < 7, perinatal death and structural malformations only occurred in women with severe polyhydramnios. CONCLUSION: It is reasonable to distinguish between mild and severe polyhydramnios regarding special attention and follow-up, as caesarean section and perinatal morbidity and mortality are related to the degree of polyhydramnios. A two-diameter pocket > or = 100 cm2 could be used to separate mild from severe cases. PMID- 17851825 TI - MRI urethrovesical junction mobility is associated with global pelvic floor laxity in female stress incontinence. AB - OBJECTIVE: To assess in a population of stress incontinent patients without genital prolapse whether urethrovesical junction mobility is associated with global pelvic floor laxity. METHODS: Dynamic MRI of 40 patients referred prior to surgery for urinary stress incontinence were reviewed retrospectively. The orientation of the urethrovesical junction was evaluated at rest and at straining in reference to the pubococcygeal line, and defined as the bladder neck pubococcygeal angle. The urethrovesical junction mobility was calculated as the difference between the bladder neck pubococcygeal angles at rest and at straining. Urethrovesical junction mobility and bladder neck pubococcygeal angles at rest and at straining were tested for correlations with the resting and straining position of different pelvic organs, urogenital hiatus size, levator plate angle, and anterior rectal bulging when straining. RESULTS: Urethrovesical junction mobility was correlated with the position of the bladder neck (p<0.0001), bladder base (p<0.0001) and uterine cervix (p<0.0001) at straining, as well as the hiatus length (p=0.0012) and width (p=0.0002), and levator plate angle (p <0.0001). The bladder neck pubococcygeal angle at rest was correlated with the resting position of the bladder neck (p <0.0001), bladder base (p <0.0001), uterine cervix (p=0.02), and the hiatus length (p=0.0004) and width (p=0.045) at rest, whereas the bladder neck pubococcygeal angle at straining was correlated with the straining position of the bladder neck (p <0.0001), bladder base (p=0.0001), uterine cervix (p <0.0001), and hiatus length (p=0.0005) and width (p=0.0004), and levator plate angle (p <0.0001) at straining. CONCLUSION: In a population of stress incontinent patients, the urethrovesical junction mobility was correlated with global pelvic floor laxity. PMID- 17851826 TI - Outcomes of temporomandibular joint disorder therapy: observations over 13 years. AB - OBJECTIVE: To evaluate the outcome of temporomandibular joint (TMJ) disorder therapy with different kinds of splints. METHODS: One-hundred-and-twenty-nine patients with TMJ disorders and meeting the primary selection criterion of reporting pain in the TMJ region were clinically evaluated. Magnetic resonance imaging of the TMJ was performed at baseline 1993-94. A protrusion splint was used whenever joint clicking could be eliminated by protrusion. In the other cases, a pivot or a Michigan splint was inserted. Re-evaluation of the patients after 12 months included a clinical examination. After 5 and 13 years, all patients were examined by means of a questionnaire. RESULTS: Pain was significantly reduced in the case of more than two-thirds of the patients 1 year after the first consultation. After 5 and 13 years, the percentages of patients with reported pain had increased only slightly. However, the therapy did not reduce joint noises or mouth opening. The prevalence of joint noises was reduced to less than a quarter after 1 year, but during the next 13 years increased to the former level. Initially, one-third of the patients had mouth-opening reduction. This proportion dropped to one-third of these cases after 1 year, but increased to 40% after 13 years. CONCLUSIONS: Treatment using splints reduced pain in approximately two-thirds of the patients, but with no difference between the three types of splints used. PMID- 17851827 TI - Effect of supplementary amine fluoride gel in caries-active adolescents. A clinical QLF study. AB - OBJECTIVE: To investigate whether supplementary daily use of amine fluoride toothpaste with weekly brushing with amine fluoride gel enhances the remineralization of white spot lesions on smooth surfaces and also to investigate the possible effect of this treatment on salivary bacterial counts and oral hygiene. MATERIAL AND METHODS: The participants comprised 135 caries-active adolescents living in suburban Stockholm. They were given an amine fluoride dentifrice (1250 ppm F) to be used twice a day, and either a test gel (4000 ppm F) or a placebo gel for brushing for 2 min once a week. During the 12-month study period, the subjects were recalled every 3rd month (baseline, 3, 6, 9, and 12 months). At each visit, DF(average change in fluorescence, in%) and lesion area (in mm2) were measured using quantitative light-induced fluorescence(QLF), followed by dietary counseling, oral hygiene instruction, and professional tooth cleaning. At baseline, 6, and 12 months, saliva was sampled for Streptococcus mutans and lactobacillus counts, and gingival bleeding index was registered. RESULTS: QLF indicated no enhancement of remineralization of white spot lesions by additional weekly brushing with amine fluoride gel. No inter-group differences emerged with regard to salivary bacterial counts. However, the oral hygiene of both groups improved, with a strong significance over time. CONCLUSION: Adjunctive weekly brushing of amine fluoride gel achieved no significant enhancement of remineralization of white spot lesions monitored with the QLF method. PMID- 17851828 TI - Association of the polymorphisms in promoter and intron regions of the interleukin-4 gene with chronic periodontitis in a Turkish population. AB - OBJECTIVES: The etiology of periodontitis is related to the interaction between micro-organisms and host responses. Host modifying factors, such as genetic predisposition, may increase the severity of periodontitis. Recent works have shown that the levels of cytokine expression are regulated by genetic polymorphisms, and that these variations can interfere with progression of the disease. This study therefore aimed to evaluate whether interleukin (IL) 4 gene polymorphisms are associated with severe generalized chronic periodontitis. MATERIAL AND METHODS: Seventy-five severe generalized chronic periodontitis patients and 73 healthy subjects were examined. Blood samples were taken and genomic DNA was amplified by polymerase chain reaction (PCR). Identification of 70 base-pair repeat polymorphisms in intron 2 and C-->T polymorphisms at -590 position of the promoter region was performed through PCR-restriction fragment length polymorphism (RFLP). RESULTS: No significant differences were found in the allele and genotype frequencies between the control and periodontitis group. CONCLUSION: The IL-4 polymorphisms were not related to severe generalized chronic periodontitis in a Turkish population. PMID- 17851829 TI - Prolonged effect of a mother-child caries preventive program on dental caries in the permanent 1st molars in 9 to 10-year-old children. AB - OBJECTIVE: To evaluate the prevalence of caries in the permanent 1st molars of a group of 9 to 10-year-old children, and to determine the long-term effect of a mother-child preventive dental program (PDP) that started when the women were pregnant and continued until the children were 6 years of age. MATERIAL AND METHODS: The permanent 1st molars of 37 children in the PDP group were evaluated for caries, both clinically and radiographically, and compared with those of a control group of 42 children who had not participated in the PDP. RESULTS: Of children in the PDP group, 70% were caries free compared to 33% in the control group (p<0.001). Of permanent 1st molars in the PDP group, 87% were caries-free compared to 61% in the control group (p<0.001). The mean DFS of the PDP children 10 years of age was 0.519+/-0.93 versus 1.57+/-1.38 for the control children (p=0.002). CONCLUSIONS: Examination of children 4 years after discontinuation of a caries preventive program reflected a long-term reduction in the DFS score of permanent 1st molars. PMID- 17851830 TI - Potential of dental adhesives to induce mucosal irritation evaluated by the HET CAM method. AB - OBJECTIVE: This study was undertaken to determine the potential of dental adhesive products to induce mucosal irritation based on their ability to damage the blood vessels of the chorioallantoic membrane (CAM) in fertilized hen's egg. MATERIAL AND METHODS: Twenty-seven dental adhesive products (total 36 solutions) covering the four adhesive concepts,etch and rinse with two or three steps procedure and self-etch with one or two steps procedure, were evaluated using the hen's egg test-CAM method (HET-CAM). The blood vessels on the CAM of a fertilized hen's egg were used as the test system, and severity of the irritation was based on an assessment of the reaction of the blood and the blood vessels to the test chemical during 5 min of exposure. Three specific end-points - coagulation of blood, lyses of blood and rupture of blood vessel - were evaluated and their time points for appearance noted. RESULTS: Coagulation of the blood was the most frequent injury, and was observed within less than a minute's exposure in 25 of the 36 tested solutions. Seventeen of the solutions were rated as moderate irritants and 16 as strong irritants. The type and severity of reaction could not be linked to the type of solvent (water, ethanol, acetone) nor to the presence of 2-hydroxylethyl methacrylate (2-HEMA) in the products. Conclusions. Most dental adhesives damage the blood vessels of the CAM, indicating irritant effects on mucous membranes. PMID- 17851831 TI - Esophageal cancer in Stockholm county 1978-1995. AB - BACKGROUND: Most studies regarding esophageal cancer are based on a selection of patients, influencing the prognosis as well as other variables measured. Sweden may be unique in that it has registries that cover the whole population, permitting population based studies regarding diseases such as esophageal cancer. This also makes it possible to study the true nature of a population of patients and to describe changes in that population over time. METHOD: Retrospective analysis of the files of all 1284 patients diagnosed with esophageal cancer in Stockholm County 1978-1995. The study period was divided into three six-year intervals (periods I, II and III). RESULTS: A total of 201 patients were diagnosed at autopsy. They were only analyzed regarding histopathological and demographic parameters. A statistically significant increased survival for the whole group of patients was found, but this improvement in survival was not found among resected patients. No survival benefit was noted for patients operated on at large centers compared to patients operated on at surgical clinics with few yearly resections performed. The well-known increase in the incidence of adenocarcinoma in the esophagus among men was documented. A tendency (non significant) of an increase in the incidence of adenocarcinoma among women was also noted. CONCLUSIONS: Survival seems to have increased among esophageal cancer patients, but this survival benefit is not dependent on improved surgery. The number of yearly operations in a clinic did not correlate to long-term survival in this study. PMID- 17851832 TI - Unusual intensification of skin reactions by chloroquine use during breast radiotherapy. PMID- 17851833 TI - Casting-type calcifications on the mammogram suggest a higher probability of early relapse and death among high-risk breast cancer patients. AB - INTRODUCTION: A retrospective analysis of the relation between the presence of casting-type calcifications on the mammogram and the prognosis of breast cancer was performed. MATERIALS AND METHODS: The mammographic tumor features and other characteristics (invasive tumor size, histological tumor type, grade, nodal, hormone receptor and HER2 status, presence of lymphovascular invasion) of 55 high risk breast cancers were studied. RESULTS: After a median follow-up time of 29.1 months, the median relapse-free survival and overall survival times among breast cancer patients with tumors associated with casting calcifications were 26.6 and 29.6 months, respectively. The corresponding parameters among patients with tumors not accompanied by casting calcifications were 54.4 and > 58.5 months, respectively. Significant associations were found between the presence of casting calcifications and the risks of relapse (HR = 3.048, 95% CI: 1.116-8.323, p = 0.030) or death (HR = 3.504, 95% CI: 1.074-11.427, p = 0.038). Positive associations were found between casting calcifications and ER/PR negativity (p = 0.015 and p = 0.003, respectively) and HER2 overexpression (p = 0.019). DISCUSSION: Our findings support the theory that breast tumors associated with casting-type calcifications at mammography comprise a disease entity which exhibits significantly more aggressive behavior and a poorer outcome than do cancers with other mammographic tumor features. PMID- 17851834 TI - Association of angiotensin-converting enzyme gene insertion/deletion polymorphism with increased risk for oral cancer. AB - INTRODUCTION: In light to recently found contribution of factors associated with thrombosis and inflammation to carcinogenesis, we investigated the possible association of angiotensin I- converting enzyme (ACE) with increased risk for oral cancer. MATERIALS AND METHODS: In DNA samples of 160 patients with oral squamous cell carcinoma and 153 healthy controls of comparable ethnicity, age and sex, we studied the insertion/deletion (I/D) polymorphism in the ACE gene, which affects its transcription. RESULTS: The I allele frequencies were significantly increased in patients compared to controls, 40.6% versus 27.5% (p < 0.001), respectively. The II homozygotes had a three-fold greater risk for developing oral cancer (odds ratio 3.17, 95% C.I. 1.32-7.61). A significant increase of I alleles was observed in patients regardless their smoking or alcohol consumption habits, early or advanced stage of cancer, presence or absence of a family history for cancer or thrombophilia (Fischer values p < 0.05). DISCUSSION: These findings suggest that the I/D polymorphism, by affecting the ACE gene expression, is associated with the progress of oral oncogenesis. PMID- 17851835 TI - Interleukin-18 gene promoter polymorphisms and the risk of esophageal squamous cell carcinoma. AB - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is multifactorial, and the genetic background may be a crucial etiologic factor. Interleukin-18 (IL-18) is a multifunctional cytokine that induces interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. Variations in the DNA sequence in the IL 18 gene promoter may lead to altered IL-18 production and/or activity, and so this can modulate an individual's susceptibility to ESCC. To test this hypothesis, we investigated the relationship of IL-18 gene promoter -137 G/C and 607 C/A polymorphisms and their haplotypes with the risk of ESCC in a Chinese population. METHODS: Two hundred and thirty five patients with ESCC and 250 age- and sex-matched controls, using sequence specific primers-polymerase chain reaction (PCR-SSP). RESULTS: Two polymorphisms, -137 G/C and -607 C/A were in strong linkage disequilibrium (LD). There were significantly differences in the genotype and allele distribution of -137 G/C polymorphism of the IL-18 gene among cases and controls. The -137 GC and CC genotypes were associated with a significantly increased risk of ESCC as compared with the -137 GG genotypes (OR = 1.91, 95% CI, 1.29-2.82, p = 0.001 and OR = 2.95, 95% CI, 1.23-7.04, p = 0.012, respectively). Consistent with the results of the genotyping analyses, the -137 C/ -607 A haplotype was associated with a significantly increased risk of ESCC as compared with the -137G/-607 C haplotype (OR = 1.61; 95% CI, 1.16-2.23; p = 0.004). CONCLUSION: This study shows for the first time an association between IL 18 gene promoter -137 G/C polymorphism may contribute represent a genetic risk factor for ESCC in a Chinese population. PMID- 17851836 TI - The nimorazole regimen in patients with head and neck cancer can increase the effect of vitamin K antagonists. PMID- 17851837 TI - Epidermal growth factor (EGF) A61G polymorphism and EGF gene expression in normal colon tissue from patients with colorectal cancer. AB - INTRODUCTION: EGF/EGFR interactions are important mechanisms behind colorectal tumour development and growth. Recently a single nucleotide polymorphism in the EGF gene has been identified (EGF A61G). It may be a potential predictor for survival of patients receiving EGFR-inhibitor cetuximab treatment, but the clinical importance and the functional influence on EGF gene expression levels in colorectal cancer (CRC) patients have not yet been further assessed. The aim of the present study was to investigate the relationship between EGF A61G genotype and EGF gene expression levels in colorectal adenocarcinomas and normal colon tissue. MATERIAL AND METHODS: Eighty-one CRC patients were included in the study. Tissue samples from normal colon, adenocacinomas and corresponding blood samples were analysed by real-time PCR for EGF gene expression and EGF A61G genotype, respectively. RESULTS: Thirty-three percent were AA, 48% and 19% A/G and G/G respectively. We found a significantly lower median age in the A/A group compared to the G/G group, suggesting a later time of diagnosis in the G/G patients. There was a significant difference between the median EGF gene expression among the three genotypes in normal colon (p < 0.001) but not in adenocarcinomas. Furthermore, the median EGF gene expression was lower in CRC tissue than in normal colon samples, (0.13 (range 0.01-6.4) vs. 0.76, (range 0.013-5.55)). CONCLUSION: We suggest that EGF A61G genotype has a functional influence on EGF gene expression in normal colon in CRC patients. The clinical implications warrant further investigations in prospective trials. PMID- 17851838 TI - Metronomic chemotherapy dosing-schedules with estramustine and temozolomide act synergistically with anti-VEGFR-2 antibody to cause inhibition of human umbilical venous endothelial cell growth. AB - The effects of 'metronomic' or extended chemotherapy dosing schedules (ECS) are mediated through poorly understood anti-angiogenic mechanisms. ECS combined with biological anti-angiogenic agents have produced promising pre-clinical results. MATERIALS AND METHODS: We have expanded the list of agents with an in vitro ECS profile to include the methylating agent temozolomide (Temodal) and the anti mitotic agent estramustine (Estracyt). These agents were also combined with a specific anti-angiogenic inhibitor IMC-1C11 and a non-specific agent with anti angiogenic properties, Compound 5h. The in vitro HUVEC ECS model system was optimised and cell proliferation assays undertaken. RESULTS: As a single agent, estramustine inhibited endothelial cell proliferation with an IC50 of 4.5 microM and was active at 10-33% of the maximum tolerated dose (MTD) from clinical schedules, whilst temozolomide had IC50 of 6.6 microM and was active at 1-6% of MTD. In combination, significant synergy was seen with IMC-1C11 in combination with either drug, whilst modest additive effects were observed with Compound 5h. None of the combinations resulted in significant cytotoxicity or apoptosis. DISCUSSION: The results show that ECS of temozolomide and estramustine can be significantly enhanced when combined with specific anti-angiogenic inhibitors in an in vitro HUVEC system. PMID- 17851839 TI - An unusual case of spontaneous acute tumor lysis syndrome associated with acute lymphoblastic leukemia: a case report and review of the literature. PMID- 17851840 TI - Atypical presentation of retinoic acid syndrome that mimics septic arthritis in a patient with acute promyelocytic leukemia. PMID- 17851841 TI - Diagnosis and treatment of primary signet-ring cell carcinoma of the prostate. PMID- 17851842 TI - Incidence of carcinoma of the oesophagus and gastric cardia. Changes over time and geographical differences. AB - BACKGROUND: The incidence of adenocarcinoma of the oesophagus is rising in many western countries including Sweden. METHODS: We have studied the latest data concerning this as well as trends in the incidence of squamous cell carcinoma and adenocarcinoma of gastric cardia. Data was extracted from the Swedish cancer registry and analyzed regarding gender, age, region, histology and location of tumour. RESULTS: The results show an increasing incidence of adenocarcinoma in both oesophagus and gastric cardia. Squamous cell carcinomas show a more stable development with a slight decrease of incidence. Adenocarcinoma is now the most common histological type of cancer in the oesophageal/cardia region in Sweden. Results also suggest a possible drift in location of adenocarcinoma from gastric cardia towards oesophagus. Overall a higher incidence was found in the male population and no trends in patient age at onset could be found. Squamous cell carcinoma is still slightly more common in urban regions. PMID- 17851843 TI - MRI demonstration of the effect of neoadjuvant radiotherapy on rectal carcinoma. AB - BACKGROUND AND PURPOSE: In patients with locally advanced rectal cancer, neoadjuvant long course (45-54 Gy in 25-30 fractions) chemoradiotherapy (CRT) may reduce tumour size and result in downstaging. In patients with primary resectable tumour short course (25 Gy in 5 fractions) radiotherapy (SCRT) reduces local recurrence but downstaging the disease or altering tumour size has not been described. We aimed to assess change in tumour size on MRI after SCRT or CRT. MATERIALS AND METHODS: Nineteen patients with rectal carcinoma underwent MRI before and after SCRT or CRT. In each case, tumour length and width were documented and number of locoregional lymph nodes recorded. Total mesorectal excision was performed in 15 patients and MR findings correlated with histopathology. RESULTS: Ten patients received SCRT and nine CRT. Tumour length reduced by 19% overall (15% following SCRT, 23% following CRT). Greater than 30% reduction (partial response) in maximum tumour thickness was seen in 4/10 (40%) following SCRT and 5/9 (56%) following CRT. CONCLUSIONS: Significant reduction in tumour size can be achieved with preoperative long course CRT and SCRT. This unexpected finding following SCRT has not been previously described. PMID- 17851844 TI - Dose-volume relationships between enteritis and irradiated bowel volumes during 5 fluorouracil and oxaliplatin based chemoradiotherapy in locally advanced rectal cancer. AB - PURPOSE: Radiation enteritis is the main acute side-effect during pelvic irradiation. The aim of this study was to quantify the dose-volume relationship between irradiated bowel volumes and acute enteritis during combined chemoradiotherapy for rectal cancer. MATERIAL AND METHODS: Twenty-eight patients with locally advanced rectal cancer received chemoradiotherapy. The radiation therapy was given with a traditional multi-field technique to a total dose of 50 Gy, with concurrent 5-Fluorouracil (5-FU) and oxaliplatin (OXA) based chemotherapy. All patients underwent three-dimensional CT-based treatment planning. Individual loops of small and large bowel as well as a volume defined as "whole abdomen" were systematically contoured on each CT slice, and dose volume histograms were generated. Diarrhea during treatment was scored retrospectively according to the NCR common Toxicity Criteria scale. RESULTS: There was strong correlation between the occurrence of grade 2 + diarrhea and irradiated small bowel volume, most notably at dose > 15 Gy. Neither irradiated large bowel volume, nor irradiated "whole abdomen" volume correlated significantly with diarrhea. Clinical or treatment related factors such as age, gender, hypertension, previous surgery, enterostomy, or dose fractionation (1.8 vs. 2.0 Gy/fraction) did not correlate with grade 2 + diarrhea. DISCUSSION: This study indicates a strong dose-volume relationship between small bowel volume and radiation enteritis during 5-FU-OXA-based chemoradiotherapy. These findings support the application of maneuvers to minimize small bowel irradiation, such as using a "belly board" or the use of IMRT technique aiming at keeping the small bowel volume receiving more than 15 Gy under 150 cc. PMID- 17851845 TI - Occult brain metastases in HER2-positive breast cancer patients: frequency and response to radiotherapy. PMID- 17851846 TI - Accelerated hyperfractionated radiotherapy and concomitant chemotherapy in small cell lung cancer limited-disease. Dose response, feasibility and outcome for patients treated in western Sweden, 1998-2004. AB - Addition of thoracic radiation therapy (TRT) to chemotherapy (CHT) can increase overall survival in patients with small cell lung cancer limited-disease (SCLC LD). Accelerated fractionation and early concurrent platinum-based CHT, in combination with prophylactic cranial irradiation, represent up-front treatment for this group of patients. Optimised and tailored local and systemic treatment is important. These concepts were applied when a new regional treatment programme was designed at Sahlgrenska University Hospital in 1997. The planned treatment consisted of six courses of CHT (carboplatin/etoposide) + TRT +/- prophylactic cranial irradiation (PCI). Standard TRT was prescribed at 1.5 Gy BID to a total of 60 Gy during 4 weeks, starting concomitantly with the second or third course of CHT. However, patients with large tumour burdens, poor general condition and/or poor lung function received 45 Gy, 1.5 Gy BID, during 3 weeks. PCI in 15 fractions to a total dose of 30 Gy was administered to all patients with complete remission (CR) and "good" partial remission (PR) at response evaluation. Eighty consecutive patients were treated between January 1998 and December 2004. Forty six patients were given 60 Gy and 34 patients 45 Gy. Acute toxicity occurred as esophagitis grade III (RTOG/EORTC) in 16% and as pneumonitis grade I-II in 10%. There were no differences in toxicity between the two groups. Three- and five year overall survival was 25% and 16%, respectively. Medica survival was 20.8 months with no significant difference between the two groups. In conclusion, TRT with a total dose of 60 to 45 Gy is feasible with comparable toxicity and no difference in local control or survival. Distant metastasis is the main cause of death in this disease; the future challenge is thus further improvement of the systemic therapy combines with optimised local TRT. PMID- 17851847 TI - Gliofibroma: a report of three cases and review of literature. PMID- 17851848 TI - Eyelid metastasis from mediastinal teratoma with malignant transformation. PMID- 17851849 TI - Selective palliative transcatheter embolization of bony metastases from renal cell carcinoma. AB - To examine whether transcatheter embolization of bone metastases is an effective palliative option for patients with renal cell carcinoma (RCCa). A retrospective review of 21 patients presenting for palliative embolization of painful RCCa skeletal metastases was performed. Details regarding anatomic sites, procedural details, and embolization materials were collected. The clinical response of the patient was assessed from clinic visits and analgesic use. Thirty separate embolization procedures were used to treat 39 metastatic lesions (18 pelvic, 8 lower extremity, 3 upper extremity, 5 rib/chest well, and 5 vertebral lesions). Five patients underwent more than one embolization. Polyvinyl alcohol was used in all 30 embolization procedures. Additional embolic materials were used in 16 of 30 procedures. A clinical response was achieved at 36 treated sites; the mean duration fo the response was 5.5 months. Selective embolization of bony renal cell carcinoma metastases can provide effective palliation in a patient population which has limited therapeutic options. PMID- 17851850 TI - Geometrical pre-planning for conformal radiotherapy. AB - The optimum selection of beams and arcs in conformal techniques is of the outmost importance in modern radiotherapy. In this work we give a description of an analytic method to aid optimum selection, which is based on minimizing the intersection between beams and organs at risk (OAR) and on minimizing the intersection between the beam and the planning target volume (PTV). An arc selection function that permits selection of irradiation arcs based on individual beam feasibility is introduce. The method simulates the treatment process by defining a computed beam feasibility, for every possible set of gantry-table angles, by taking into account accurately computer intersection volumes between the OAR and beams. The beams are shaped to conform the target using realistic parameters for the treatment process. The results are displayed on a virtual sphere centred at the isocenter with color-coded regions indicating beam feasibility. Arcs selections are performed by searching the map for successive gantry positions at a certain table angle, with feasibility values greater than a user-specified threshold. The accuracy of the method was confirmed by using geometrical regular shapes, as well as real clinical cases. PMID- 17851851 TI - Absence of JH2 domain mutation of the tyrosine kinase JAK2 in renal cell carcinomas. PMID- 17851852 TI - Radiotherapy in oncological emergencies--final results of a patterns of care study in Germany, Austria and Switzerland. AB - Radiotherapy (RT) is an important treatment option for emergencies in oncology. A multicenter patterns of care study (PCS) was conducted in all RT institutions in Germany, Austria and Switzerland. In 2003 a standardized structured questionnaire was sent to all RT institutions. Number and type of staff involved, number of patients, over time distribution and expense, treatment indications and concepts of emergency RT were assessed. In addition, treatment outcome for the different indications was evaluated. The PCS was structured and analyzed according to the model for quality assessment set up by Donabedian in three major components: structure, process and outcome. One hundred and forty institutions (70%) answered the questionnaire. For the baseline of 2003 a total of 3244 emergency radiotherapy indications with a mean of 28 per institution were reported. Forty percent of all institutions provide a special 24 h service at night or weekends. Seventy percent of the emergency indications were irradiated between Monday and Thursday, 30% between Friday and Sunday. Ninety percent of all emergencies were referred to RT between 8 a.m. and 6 p.m., 10% between 6 p.m. and 8 a.m. The applied doses for emergency RT ranged between 2 Gy and 8 Gy (median: 3.5 Gy). Time expense was reported with a median of 90 min. The outcome analysis based on the treatment results of 1 033 patients: There was an improvement of myelocompression in 50% of the cases, vena cava superior compression in 70%, bronchial obstruction in 70% and bleedings in 80%. A clear dose-response relationship could not be established, but single doses of over 3 Gy in vena cava superior syndrome exhibited a significant advantage. This study represents the largest database in literature on emergency RT. RT was shown to be fast, time sparing and a very effective treatment option for special oncological emergencies. PMID- 17851853 TI - Gemcitabine and cisplatin in locally advanced and metastatic bladder cancer; 3- or 4-week schedule? AB - BACKGROUND: Chemotherapy with gemcitabine and cisplatin (GC) is an active regimen in advanced transitional cell carcinoma (TCC). Traditionally, GC has been administered as a 4-week schedule. However, an alternative 3-week schedule may be more feasible. Long-term survival data for the alternative 3-week schedule and comparisons of the feasibility and toxicity between the two schedules have not previously been published. MATERIAL AND METHODS: We performed a retrospective analysis of patients with stage IV TCC, treated with GC by a standard 4-week or by an alternative 3-week schedule. RESULTS: A total of 212 patients received GC (3-week; n = 151, 4-week; n = 61). We found no statistical differences in overall survival between the two schedules (hazard ratio 1.15, 95% CI 0.83-1.59), p = 0.40). Five-year survival rates were 14.9% and 11.8% for the 3- and 4-week schedule, respectively (p = 0.94). Response rates were 59.7% and 55.6%, respectively (p = 0.61). Toxicity was less pronounced in the 3-week schedule with regards to neutropenia, thrombocytopenia, and transfusion rates. Hematologic toxicity at day 15 in the 4-week schedule was common, leading to dose omissions in 47% of cycles. Dose intensity for gemcitabine was accordingly lower in the 4 week-schedule. The higher dose intensity of cisplatin in the 3-week schedule, did not lead to increased renal toxicity. In 13 patients with impaired renal function, cisplatin was split into 2 days, which was feasible and efficient. CONCLUSION: Efficacy parameters for the GC 3-week schedule were comparable to those for the 4-week schedule, whereas toxicity was less pronounced. The 3-week schedule may be an effective and feasible alternative GC-schedule. PMID- 17851854 TI - Radiation-induced oesophageal carcinoma after breast carcinoma: a report of five cases including three successfully treated by radiochemotherapy. PMID- 17851855 TI - Patient assessed symptoms are poor predictors of objective findings. Results from a cross sectional study in patients treated with radiotherapy for pharyngeal cancer. AB - INTRODUCTION: The aim of the study was to assess the value of the EORTC questionnaires C30 and H&N35, as an instrument for the study of side effects. PATIENTS AND METHODS: We invited all recurrence free patients, treated with radical radiotherapy for pharyngeal cancer between 1998 and 2002 at our institution, to participate in the study. Data was retrieved using questionnaires, functional endoscopic evaluation of swallowing, dental examination with orthopantomography and saliva flow measurements. Thirty-five (55% of invited) participated. RESULTS: Side effects were omnipresent and often severe. The value of patient assessed symptom scores to predict equivalent objective changes was varied: We found a sensitivity of 0.59-0.93, specificity of 0.40-0.81, positive predictive value of 0.28-0.81 and a negative predictive value of 0.46-0.94. CONCLUSION: The questionnaire should be used to retrieve information on subjective side effects and objective examination should be used for objective changes. One cannot conclude from one to the other. PMID- 17851856 TI - No association between TNF-alpha-238 polymorphism and colorectal cancer in Iranian patients. PMID- 17851857 TI - A 25-year follow-up of a population screened with faecal occult blood test in Finland. AB - The aim of the study was to assess the feasibility of and possible selection to attend in colorectal cancer screening. MATERIAL AND METHODS: During the years 1979-1980, 1 785 men and women (born in 1917-1929) were invited to a pilot screening project for colorectal cancer. The screening method used was a guaiac based faecal occult blood test repeated once if the initial test was positive. RESULTS: Compliance was 69% and the test was positive in 19% of those attending. In a record linkage with the Finnish Cancer Registry, 47 colorectal cancer cases and 24 deaths from colorectal cancer were observed by the end of 2004. In all, the particular test method was not regarded specific enough for population screening. There was, however, no difference in cancer incidence between those who complied and those who did not when compared to the general population of same age and gender. CONCLUSION: Compliance was found high enough to make screening feasible and there was no self selection of persons with low cancer risk to attend screening. PMID- 17851858 TI - Daily low-dose/continuous capecitabine combined with neo-adjuvant irradiation reduces VEGF and PDGF-BB levels in rectal carcinoma patients. AB - Metronomic low-dose chemotherapy regimen was found to have an antiangiogenic effect in tumors. However, its effect on levels of circulating pro-angiogenic and anti-angiogenic factors is not fully explored. MATERIALS AND METHODS: The levels of both VEGF and PDGF-BB were measured in three time points, in the serum of 32 rectal carcinoma patients receiving daily reduced-dose/continuous capecitabine in combination with preoperative pelvic irradiation. RESULTS: We found a significant decrease in VEGF and PDGF-BB serum levels during the combination treatment (p < 0.0001), followed by an increase in the successive rest-period (p < 0.0001). In addition, substantial changes in platelets counts were observed during treatment in correlation with the changes of VEGF and PDGF-BB serum levels. DISCUSSION: These results suggest that combined chemo-irradiation affect levels of pro angiogenic factors during treatment, and may reflect an anti-angiogenic window induced during this treatment. The potential implications of this inducible phenomenon, including a possible clinical benefit from the administration of long lasting metronomic chemotherapy immediately following combined chemo-irradiation, would warrant further investigation. PMID- 17851859 TI - Surgical specimen can be replaced by core samples in assessment of ER, PR and HER 2 for invasive breast cancer. AB - OBJECTIVE: To compare 14-gauge SCNB (stereotactic core needle biopsy) with surgery and to investigate tissue-heterogeneity of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth-factor receptor (HER-2) for nonpalpable breast cancers. To determine the number of cores needed for assessment of these factors. MATERIALS AND METHODS: Cores of 41 invasive cancers were collected in three containers: the 1st into A, the 2nd and 3rd into B and subsequent cores into C. ER, PR and HER-2 were scored by immunohistochemistry and if 2+ or 3+, by chromogenic-in-situ-hybridisation (CISH) for containers and for surgical specimen. RESULTS: Between SCNB and surgical specimen concordance was 83% (kappa = 0.39) for ER, 88% (kappa = 0.69) for PR and HER-2 and 93% (kappa = 0.63) for HER-2 after CISH. For the most discordant cases, status was positive in cores but negative in surgery: 5/7 for ER (p = 0.459), 5/5 for PR (p = 0.063), and 4/5 for HER-2 (p = 0.375), after CISH 3/3 (p = 0.250), but the difference was not statistically significant. Concordances between containers of cores was 100% (kappa = 1), 85% (kappa = 0.66) and 85% (kappa = 0.66), respectively. With more than three cores, sensitivities of 95%, 100% and 100% were reached. CONCLUSIONS: SCNB is at least as sensitive as surgery in assessment of ER, PR and HER-2. Three cores are needed for reliable assessment of HER-2 after adding CISH and more than three cores for PR, possibly due to tissue heterogeneity. For ER sensitivity remained lower, 95%, even in multiple cores, therefore ER-negative cases should be further investigated from surgical specimens. PMID- 17851860 TI - Effects of blood transfusion with leucocyte depletion on length of hospital stay, respiratory assistance and survival after curative surgery for colorectal cancer. AB - PURPOSE: To investigate effects of blood transfusion, with/without leucocyte depletion, on duration of hospital stay, need for respiratory support, mortality and long-term survival after curative surgery for colorectal cancer. METHODS: The trial was a prospective, randomised, multicenter study. Six hundred and forty two patients with colorectal cancer were included. Blood transfusion was given when needed during and/or after operation, randomised to packed red blood cells (RBC) or leucocyte-depleted red blood cells (LDB) using leucocyte filtration. Assisted ventilation in ICU, hospital stay, malignant and nonmalignant specific mortality and overall survival were outcome measures. RESULTS: The RBC group had higher need for assisted ventilation post-operatively (8.1% vs. 3.6%) and significantly higher proportion of patients with prolonged (> 20 days) hospital stay. After median follow-up time of 99.5 months there was no significant difference in mortality or long-term survival between the groups. The median cumulative survival time of 55 months in LDB vs. 36 months in RBC group did not reach significance level. Non-transfused patients had a significantly lower proportion of prolonged hospital stay, and significantly increased survival, compared to transfused patients. CONCLUSION: Leucocyte depleted transfusions improved the postoperative course following surgery for colorectal cancer, compared with packed red blood cell transfusions. PMID- 17851861 TI - Factors associated with increased breast cancer-related lymphedema volume. AB - BACKGROUND: Upper limb lymphedema occurs in approximately 15-20% of women after breast cancer treatment. We analysed the factors associated with lymphedema volume. METHOD: Cross-sectional study of 807 patients with secondary arm lymphedema was performed in a single lymphology unit. Data collected included patient characteristics, characteristics of breast cancer treatment, past history of cellulitis, Body Mass Index, delay from cancer to onset of lymphedema and duration of lymphedema. Lymphedema volume was calculated for each 5-cm segment by utilizing the formula for a truncated cone. Univariate and multivariate regression models were fitted to study the factors associated with increased lymphedema volume. RESULTS: In univariate analysis, factors associated with lymphedema volume were duration of lymphedema, Body Mass Index, mastectomy, and past history of cellulitis. Treatment with anti-estrogen drugs was negatively associated with lymphedema volume (p = 0.02). In multivariate analysis, factors associated with lymphedema volume were duration of lymphedema (p < 0.001), Body Mass Index (p < 0.001), delay from cancer to onset of lymphedema (p = 0.002), mastectomy (p = 0.02) and past history of cellulitis (p = 0.011). CONCLUSION: Early diagnosis and management of lymphedema, weight control and advices to avoid cellulitis are the main controllable parameters in women to prevent severity of breast cancer-related lymphedema. PMID- 17851862 TI - Risk of isolated nodal failure for non-small cell lung cancer (NSCLC) treated with the elective nodal irradiation (ENI) using 3D-conformal radiotherapy (3D CRT) techniques--a retrospective analysis. AB - PURPOSE: To estimate retrospectively the rate of isolated nodal failures (INF) in NSCLC patients treated with the elective nodal irradiation (ENI) using 3D conformal radiotherapy (3D-CRT). MATERIALS/METHODS: One hundred and eighty-five patients with I-IIIB stage treated with 3D-CRT in consecutive clinical trials differing in an extent of the ENI were analyzed. According to the extent of the ENI, two groups were distinguished: extended (n = 124) and limited (n = 61) ENI. INF was defined as regional nodal failure occurring without local progression. Cumulative Incidence of INF (CIINF) was evaluated by univariate and multivariate analysis with regard to prognostic factors. RESULTS: With a median follow up of 30 months, the two-year actuarial overall survival was 35%. The two-year CIINF rate was 12%. There were 16 (9%) INF, eight (6%) for extended and eight (13%) for limited ENI. In the univariate analysis bulky mediastinal disease (BMD), left side, higher N stage, and partial response to RT had a significant negative impact on the CIINF. BMD was the only independent predictor of the risk of incidence of the INF (p = 0.001). CONCLUSIONS: INF is more likely to occur in case of more advanced nodal status. PMID- 17851863 TI - Changes in alcohol intake and risk of upper digestive tract cancer. AB - INTRODUCTION: Alcohol intake measured at one point in time is a strong predictor for later development of cancer of the oral cavity, pharynx, larynx and esophagus. In this prospective cohort study, we examined whether changes in individual alcohol intake resulted in subsequent altered risk of these cancers. MATERIAL AND METHODS: In the Copenhagen City Heart Study we assessed alcohol intake among 4 896 men and 6 239 women who participated at both the first (1976 1978) and second (1981-1983) examination of the study. Alcohol intake changes on risk of upper digestive tract cancer 1981-2002 were examined by a Cox model adjusted for potential confounders. RESULTS: Despite a small number of cases (n = 105), alcohol intake increase > 14 drinks/week was associated with significantly elevated risk (hazard ratio = 2.5; 95% confidence interval, 1.1-5.3), while suggestively decreased risk was observed for persons lowering alcohol intake > 7 drinks/week (0.5; 0.1-2.5). The trend test was highly significant (p < 0.0001). CONCLUSIONS: These findings support public health messages of not increasing alcohol intake and lowering consumption among people with high alcohol intake. PMID- 17851864 TI - High-intensity strength training improves quality of life in cancer survivors. AB - INTRODUCTION: Cancer rehabilitation programs mainly involve endurance training, and little attention is paid to strength training. Cancer survivors are generally advised to train at much lower workloads than the standard guidelines for strength training suggest. The purpose of this study is to evaluate the effectiveness of an 18-week high-intensity strength training program in cancer survivors. METHODS: Fifty-seven patients (age 24 to 73 years) who had received chemotherapy for lymphomas, breast, gynecologic, testicular, or colorectal cancer completed the program. Outcome measures were changes in muscular strength (one repetition maximum), cardiopulmonary function (VO2 max), maximal short exercise capacity (MSEC), body composition and health-related quality of life (HRQOL) between baseline and follow-up. DISCUSSION: The high-intensity strength training was well tolerated by all patients. Significant improvements in muscle strength were found, with effect sizes varying from 1.32 to 2.68. VO2 max increased significantly by 10% in men and by 13% in women. Different functional scales of HRQOL improved (p < 0.01), with effect sizes varying from 0.47 to 0.82. Muscle strength correlated significantly with physical functioning before and after the training program. CONCLUSION: We conclude that a supervised, high-intensity strength training program seems to be an effective means to improve muscle strength, cardiopulmonary function, and HRQOL and should be incorporated in cancer rehabilitation programs. Further randomized trials are needed to confirm the results. PMID- 17851865 TI - Consequences of inadvertent radioiodine treatment of Graves' disease and thyroid cancer in undiagnosed pregnancy. Can we rely on routine pregnancy testing? AB - INTRODUCTION: Radioiodine and most cytostatic treatments are contraindicated in pregnancy. Still, inadvertent therapy does occur. Radioiodine was given to two pregnant women with Graves' disease and thyroid cancer respectively, both in their 20th gestational week. Routine pregnancy tests based on urinary beta-hCG had failed to indicate pregnancy in both cases. METHODS: Estimation of doses to the foetuses and foetal thyroids. Scrutiny of pregnancy testing. RESULTS AND CONCLUSIONS: Doses to foetal thyroids were ablative (250-600 Gy). Total foetal dose in the Graves' patient was 100 mGy and compatible with survival, whereas a foetal dose of approximately 700 mGy together with induced hypothyroidism was fatal for the foetus of the cancer patient. Routine pregnancy tests may fail early and late in pregnancy. The possibility of pregnancy should be considered in all fertile women before therapy with radionuclides or cytostatic regimens, and a clinical investigation undertaken on wide indications with determination of serum beta-hCG, preferably together with an ultrasound examination. PMID- 17851866 TI - Selective in vitro cytotoxic effect of human cancer cells by bluetongue virus-10. AB - Bluetongue viruses (BTVs) infect primarily domestic cattle and wild ruminants but have never been shown to infect normal human cells. Thus, humans are sero negative towards BTVs. The selective and differential effects of BTV serotype 10 (BTV-10) infection were investigated with five cell lines including primary human embryo lung fibroblast (HEL) and primary murine embryos fibroblast(MEF), human hepatic carcinoma 3B cell line (Hep-3B), human lung carcinoma cell line (A549) and mouse fibroblast cell line (NIH 3T3). In this study, comparative analyses of differential cytopathic effects (CPEs), survival rates using different Multiplicities of Infection (MOI), ultra-structural changes by transmission electron microscopy, and the preferential cell cycle changes of infected cells by flow cytometry were made among these cells. Detection of the presence of BTV genome and kinetic analysis of virus titers in TCID50 were also made. We provided the first analytical demonstration and evidence that BTV-10 could selectively infect and degrade human cancer cells but not cultured primary normal cells. No CPE or viral mRNAs could be detected within these normal cells, while various degrees of CPE could be found in Hep-3B and A549, as well as in NIH 3T3 under similar conditions. Before death, BTV-infected human cancer cells were directly arrested in the sub-G1 phase and the diversity of BTV infection as shown by the MTT method had significant difference (F = 95.635, p < 0.01). Above results suggested that this viral dose-dependent cytotoxic effect is caused by both effective virion amplification and induced apoptosis. Cellular distinctive transformation status may contribute to the selectivity. Thus, selective degradation of human cancer cells but not normal diploid cells by the newly discovered oncolytic potential of BTV would provide a very attractive approach for cancer therapy in the future. PMID- 17851867 TI - Will haptic feedback speed up medical imaging? An application to radiation treatment planning. AB - Haptic technology enables us to incorporate the sense of touch into computer applications, providing an additional input/ output channel. The purpose of this study was to examine if haptic feedback can help physicians and other practitioners to interact with medical imaging and treatment planning systems. A haptic application for outlining target areas (a key task in radiation therapy treatment planning) was implemented and then evaluated via a controlled experiment with ten subjects. Even though the sample size was small, and the application only a prototype, results showed that haptic feedback can significantly increase (p < 0.05) the speed of outlining target volumes and organs at risk. No significant differences were found regarding precision or perceived usability. This promising result warrants further development of a full haptic application for this task. Improvements to the usability of the application as well as to the forces generated have been implemented and an experiment with more subjects is planned. PMID- 17851868 TI - Incidence and tumor characteristics of breast cancer diagnosed before and after implementation of a population-based screening-program. AB - BACKGROUND: Randomized controlled trials and service screening programs have shown that breast cancer screening reduces the mortality from the disease. Several years of monitoring are needed to prove such an effect. In the meantime attention should be paid to early surrogate measures, such as histopathological tumor characteristics. The Norwegian Breast Cancer Screening Program started November 1995. This study compares incidence, prognostic tumor characteristics and surgical treatment in breast cancer cases diagnosed in the pre-screening (1987-1995, n=2 618) and screening period (1996-2004, n=5 417), in women aged 50 69 years, residing in the first four counties implementing the screening program. The screening period is divided into those invited versus those not invited to the screening program, and those exposed (participants) versus those not exposed to the program (non-participants). RESULTS: The incidence of invasive breast cancer rose from 170 per 100 000 women years (wy) in 1987 to 355 per 100 000 wy in 1997. The proportion of DCIS was 5% in the pre-screening period, and 14% in the screening period. Tumors 20 mm or less were diagnosed in 56% of the invasive cases in the pre-screening period, in 74% of the invited, and in 77% of the exposed women. The relative risk of diagnosing breast cancer with metastases was 0.85 (95% CI 0.84-0.87) for invited and 0.82 (95% CI 0.81-0.84) for exposed women, relative to those diagnosed in the pre-screening period. Ablation was performed in 85% of the invasive cases diagnosed in the pre-screening period, and in 45% of the cases in the screening period. CONCLUSION: Breast cancer diagnosed in the screening period had prognostically favorable tumor characteristics compared to breast cancer diagnosed in the pre-screening period. Implementation of organized population based screening and the time trend are considered possible reasons. PMID- 17851869 TI - Techniques of tumour bed boost irradiation in breast conserving therapy: current evidence and suggested guidelines. AB - Breast conservation surgery followed by external beam radiotherapy to breast has become the standard of care in management of early carcinoma breast. A boost to the tumour bed after whole breast radiotherapy is employed in view of the pattern of tumour bed recurrences in the index quadrant and was particularly considered in patients with some adverse histopathological characteristics such as positive margins, extensive intraductal carcinoma (EIC), lymphovascular invasion dose in patients even without such factors and for all age groups. The maximum absolute reduction of local recurrences by the addition of boost is especially seen in young premenopausal patients. At the same time, the addition of boost is associated with increased risk of worsening of cosmesis and no clear cut survival advantage. Radiological modalities such as fluoroscopy, ultrasound and CT scan have aided in accurate delineation of tumour bed with increasing efficacy. A widespread application of these techniques might ultimately translate into improved local control with minimal cosmetic deficit. The present article discusses the role of radiotherapy boost and the means to delineate and deliver the same, identify the high risk group, optimal technique and the doses and fractionations to be used. It also discusses the extent of adverse cosmetic outcome after boost delivery, means to minimise it and relevance of tumour bed in present day scenario of advanced radiotherapy delivery techniques like Intensity modulated radiation therapy (IMRT). PMID- 17851870 TI - LRIG1 expression in colorectal cancer. AB - In the present study the expression of LRIG1 (leucine rich repeats and immunoglobin-like domains 1) and its relation to EGFR (epidermal growth factor receptor) was examined in tumour samples and adjacent non-neoplastic tissues from 30 patients with colorectal cancer. The LRIG1 gene, at chromosome 3p14, encodes an intergral membrane protein, which counteracts signalling by receptor tyrosine kinases belonging to the ERBB (epidermal growth factor receptor) family. LRIG1 is expressed in all tissues and organs analysed to date, including breast, brain, skin, kidney, spleen and colon. Overexpression of EGFR is seen in 70 - 90% of colorectal cancers, and is associated with a poor survival. Western blot analysis showed LRIG1 upregulation in 43% and downregulation in 43% of the colorectal cancers compared to adjacent non-neoplastic tissue. No correlation was evident between LRIG1, analysed by Western Blot and the expression of EGFR analysed by immunohistochemistry. FISH (fluoroscence in situ hybridisAtion) analysis showed increased LRIG1 copy number in one of nine tumours. Four colorectal cancer cell lines demonstrated two LRIG1 gene copies. In conclusion, there was a great heterogeneity in the expression of the LRIG1 protein in colorectal cancer, which was not related to gene dosage of the LRIG1 gene. Further studies can be of interest to evaluate whether alteration in LRIG1 expression in colorectal cancer is of biological or clinical significance. PMID- 17851871 TI - The Late Effects Clinic in action: for survivors of childhood malignancy. AB - BACKGROUND: Long-term survivors of childhood malignancy are a newly emergent patient group with a unique but wide range of survivorship issues. There are rising demands for long-term, medical follow-up and social support for this potentially vulnerable group. These demands stem from improving survival rates and the progressively increasing incidence of late physical, psychological and social sequelae. CASE-STUDIES AND DISCUSSION: The ideal method to facilitate this long-term followup is unclear, and faces the problems of health-care system limitations coupled with the paucity of outcomes-based research to guide evidence based, clinical practice. We discuss how the Late Effects Clinic operates in our institution: optimising the involvement of the multi-disciplinary medical and allied health care teams to meet the physical and psychological needs of long term survivors, and to assist with the social issues surrounding survivorship. This model involves a co-operative team approach, thereby alleviating the sole responsibility from general practitioners or individual physicians with a restricted realm of expertise. We present three case reports illustrating the value of a formal late effects follow-up programme, and demonstrating the integration of the Late Effects Clinic into medical practice. PMID- 17851872 TI - Loss of histidine decarboxylase as a marker of malignant transformation and dedifferentiation of B-cells infiltrating the skin. A case report of a therapy resistant multiple myeloma complicated by skin infiltration. PMID- 17851873 TI - Secondary acute lymphoblastic leukaemia following oxaliplatin for adjuvant chemotherapy in colon cancer. PMID- 17851874 TI - Primary low grade follicular lymphoma of cranial vault mimicking lipoma at presentation. PMID- 17851875 TI - Parent distress in childhood cancer: a comparative evaluation of posttraumatic stress symptoms, depression and anxiety. AB - The aim was to assess symptoms consistent with posttraumatic stress (PTS; cognitive intrusions, avoidance, arousal) related to the child's illness, and generic distress (anxiety, depression) in parents of childhood cancer patients. Outcomes were compared to normative and relevant reference data, and analysed for their dependence on time passed since diagnosis. Swedish parents (266 mothers, 208 fathers) were recruited at two centres. Data from a clinical sample of posttraumatic stress disorder (PTSD) patients and parents of healthy children were used for comparison. The Impact of Events Scale (IES-R) was used for assessing PTS symptoms, and self-report scales for anxiety and depression. Elevated stress and generic distress varied as a function of time from diagnosis. Up to 12% of parents for whom >5 years had passed since diagnosis still reported equally, or more intrusive thoughts, avoidance and arousal when contrasted to patients suffering from PTSD. Parents of recently diagnosed children had more cancer-related intrusive thoughts than those of long-term survivors. Heightened anxiety and depression was most prominent in mothers and fathers up to 2.5 years after diagnosis. In conclusion, severe generic distress characterises the first years after diagnosis, and initially common PTS symptoms are found in a considerable portion of parents years after diagnosis. Clinically, attention should be paid to continuous parent support needs. Individual variation vis-a-vis distress vulnerability should be acknowledged, and presupposed gender differences avoided. When treatment situation asks the most of parents' collaboration, many are under pressure of severe stress. PMID- 17851876 TI - Deafness associated with the use of Bortezomib in multiple myeloma. PMID- 17851877 TI - Effect of interferon and 5-fluorouracil on serum VEGF levels in neuroendocrine tumours. PMID- 17851878 TI - Effective palliation without normal tissue toxicity using low-dose ultrafractionated re-irradiation for tumor recurrence after radical or adjuvant radiotherapy. PMID- 17851879 TI - Accuracy of MRI for estimating residual tumor size after neoadjuvant chemotherapy in locally advanced breast cancer: relation to response patterns on MRI. AB - BACKGROUND: This study evaluated the accuracy of magnetic resonance imaging (MRI) for estimating residual tumor size after neoadjuvant chemotherapy in patients with locally advanced breast cancer and assessed whether the tumor pattern on MRI after chemotherapy influenced the accuracy of the MRI measurement of the residual tumor size. PATIENTS AND METHODS: Fifty patients who received neoadjuvant chemotherapy with doxorubicin and docetaxel for locally advanced breast cancer were evaluated with MRI before and after chemotherapy. We compared the residual tumor size measured by MRI with the pathologically determined size and investigated the influence of the residual tumor pattern on MRI (shrinkage, nest or rim, and mixed) and pathologic characteristics on the accuracy of the MRI measurement. RESULTS: The correlation coefficient between the residual tumor sizes determined by MRI and by pathology was 0.645. The MRI measurement agreed with the pathologically determined size in 36 patients (72%) and disagreed in 14 patients 928%), overestimating the size in 13 (26%) and underestimating the size in one (2%). disagreement appeared to be more frequent in the cases showing a nest or rim pattern than in those exhibiting a shrinkage pattern, although this was not statistically significant (p = 0.119). CONCLUSIONS: MRI is an accurate method for predicting the extent of residual tumor after neoadjuvant chemotherapy; however, it may overestimate the residual disease, especially in cases showing a nest or rim tumor pattern and in those having combined lesions with ductal carcinoma in situ or multiple scattered nodules after neoadjuvant chemotherapy. PMID- 17851880 TI - Incidence and characteristics of peripheral neuropathy during oxaliplatin-based chemotherapy for metastatic colon cancer. AB - AIM: The current prospective study sought to trace the incidence and severity of oxaliplatin-induced peripheral neuropathy (OXLIPN) and to determine its clinical and electrophysiological pattern. PATIENTS AND METHODS: Twenty-five adult patients scheduled to be treated with 12 courses of the oxaliplatin-based regimen, FOLFOX-4, for metastatic colon cancer participated in this study. Patients were clinically and electrophysiologically monitored at baseline and followed-up during chemotherapy. The severity of OXLIPN was summarized by means of a modified Total Neuropathy Score (TNS). RESULTS: Evidence of OXLIPN was disclosed in 16 of the 25 patients (64%). The mean TNS values for patients manifesting some grade of OXLIPN were 13.9 +/- 5.8 (range 7-28). All longitudinal comparisons concerning the motor conduction parameters failed to reach significance. By contrast, comparisons of the median changes at baseline and each of the follow-up studies revealed significant decrease in all sensory action potentials examined. CONCLUSION: Our results indicate that the majority of patients treated with the FOLFOX-4 regimen would manifest an axonal, predominately sensory peripheral neuropathy, of mild to moderate severity. PMID- 17851883 TI - Squamous cell carcinoma of the oral tongue in young patients: a matched-pair analysis. AB - CONCLUSIONS: Young patients with squamous cell carcinoma (SCC) of the oral tongue developed fewer locoregional recurrences. The overall survival and disease specific survival rates were better in the young patient population. OBJECTIVES: To compare the survival rates of patients under 45 years of age and diagnosed with SCC of the oral tongue with those of patients older than 45 years. PATIENTS AND METHODS: A retrospective review of 20 patients under 45 years of age with SCC of the oral tongue was performed. These patients were matched to an older population by sex and clinical stage. Overall survival, disease-free survival, disease-specific survival, and rates of local, regional and distant metastases were determined for both populations. RESULTS: Stage and treatment modality were similar in the two age groups. There were significant differences in overall survival (p=0.013) and disease-specific survival (p=0.046) favoring young patients. Rates of locoregional recurrence and distant metastasis were higher in the older patients. PMID- 17851884 TI - Successful palliative chemotherapy for peristomal recurrence of laryngeal metastasis from colon adenocarcinoma. PMID- 17851885 TI - The prevalence and clinical course of patients with 'incidental' acoustic neuromas. AB - CONCLUSIONS: This study suggests that among patients diagnosed with 'incidental' acoustic neuromas (ANs), a substantial portion are discovered incidentally. Small and medium-sized ANs that are found incidentally may have a more benign nature, and may be less likely to require interventions. OBJECTIVE: To estimate the prevalence of ANs, and to compare the prognosis and progression of the disease between those diagnosed incidentally verse symptomatically with an AN. PATIENTS AND METHODS: This was a retrospective evidence-based case series of patients with AN treated at a tertiary medical center between November 1999 and January 2005. An MRI with gadolinium was performed on all patients to establish the diagnosis of AN. A medical chart review of these patients was searched for sex distribution, age, presenting symptoms, hearing loss, speech discrimination scores, tumor characteristics by imaging, intervention performed, and time between diagnosis and intervention. The studied population was divided into those patients with pre-imaging audiovestibular symptoms provoking a clinical suspicion of AN (symptomatic group) and those without a pre-imaging suspicion of AN (incidental group). RESULTS: The charts of 120 patients with ANs were analyzed and categorized as either incidentally or symptomatically discovered. Incidentally discovered ANs accounted for 12% of patients with the diagnosis of AN in our population. The average age at diagnosis was 55.7 and 52.8 years (p = 0.50) in the symptomatic and incidental groups, respectively. The gender distribution was not different between the groups (p = 0.08). Audiometry revealed a speech discrimination score asymmetry greater in the symptomatic group (p < 0.0001). Tumor size by imaging performed at diagnosis in the incidental population was 1.09 cm on average, compared with 1.5 cm in the symptomatic patients (p = 0.08). A greater proportion of patients with symptomatically discovered AN underwent intervention by surgical resection, stereotactic radiosurgery, or radiation compared with patients with incidentally discovered AN (76% versus 47%, p = 0.02). PMID- 17851886 TI - Nitric oxide synthase inhibitor reduces noise-induced cochlear damage in guinea pigs. AB - CONCLUSION: The results obtained in this study indicate that NG-nitro-L-arginine methyl ester (L-NAME) protects cochlear damage from acoustic trauma through reducing the production of nitric oxide (NO). OBJECTIVES: This study aimed to explore whether NO synthase inhibitor L-NAME could reduce cochlear damage in acoustic trauma. MATERIALS AND METHODS: Seventy guinea pigs (300-350g) were divided randomly into four groups (n=20 in groups I, III, and IV; n=10 in group II). Two days consecutively and 30min before noise exposure (4kHz octave band, 115dB SPL 5h), subjects received an injection of 5ml saline/kg (groups I and III) or 10mg/kg L-NAME (groups II and IV). Sham-exposed guinea pigs were listed as groups I and II. Protection was assessed physiologically by the change in auditory brainstem response (ABR) threshold and histologically by survival of outer hair cells (OHCs). NO level of cochlear tissue was assayed 3days after noise exposure. RESULTS: Group III showed significantly greater OHC loss, threshold shifts and NO level compared with group I and group IV. Compared with group III, noise-induced elevation in NO level in the cochlea was significantly attenuated by L-NAME (p<0.001). PMID- 17851887 TI - Spontaneous nystagmus and canalithiasis preceding a loss of vestibular function. AB - The patient, a 45-year-old female with Meniere's disease, was submitted to endolymphatic sac surgery because of frequent spells of vertigo. The day after surgery she became dizzy and lost the hearing in the operated ear. She presented with a brisk nystagmus towards the healthy ear; however, a remaining vestibular function on the operated side was still present. The head impulse test was normal and in the positioning test, when turning to the operated ear, the spontaneous nystagmus was replaced by a transient horizontal nystagmus in the opposite direction. It is likely that this geotropic nystagmus was elicited from the operated ear because of debris that had accumulated in the lateral semicircular canal. Due to a suspicion of post surgical edema, the patient was treated with prednisolone, but the progression of the lesion could not be arrested. The signs of canalithiasis disappeared, but the head impulse test became pathologic as did the caloric reaction. The patient remained deaf in the operated ear. PMID- 17851888 TI - Temporal bone pathological study on maxillary sinus carcinoma with bilateral temporal bone metastasis. AB - We report a case in which metastasis occurred from a left-side maxillary carcinoma to bilateral temporal bones through different routes, manifested by rapidly progressing left-side mixed hearing loss, left-side vestibular dysfunction, and serous otitis media. Later the left-side hearing threshold became severely elevated, suggesting profound sensory hearing loss. Histopathology of the temporal bones revealed that the side with the lesion was severely damaged by tumor through direct and hematogenous metastasis. On the contralateral side, it showed four findings: (i) sparse and separate tumor invasion of the petrous bone, the mastoid cavity, and the facial canal (hematogenous spread); (ii) tumor involvement in the lower part of the cochlear aqueduct without invasion of the internal acoustic canal or cochlea, implying early meningeal carcinomatosis; (iii) vascular stria atrophy, spiral ganglion diminution, and well preserved hair cells; and (iv) diffuse effusion in the middle ear and mastoid cavity. Our observations revealed that tumor cells dispersed to the same side through different routes, whereas early metastasis to the contralateral side was mainly through hematogenous and subarachnoid spread. PMID- 17851889 TI - Cogan's syndrome: a case report. AB - Cogan's syndrome is a rare autoimmune disorder connecting ophthalmologic and audiovestibular signs. A case of a young patient is reported, describing the evolution of her illness, and diagnostic and therapeutic measures performed. Response to treatment, including glucocorticoid therapy and hyperbaric oxygenation, is discussed. A synoptic review of knowledge of this rare disorder is incorporated. PMID- 17851890 TI - Concurrent chemoradiotherapy with carboplatin and uracil-f tegafur (UFT) for patients with poor performance status with locally advanced squamous cell carcinoma of the head and neck (SCCHN). AB - CONCLUSIONS: Concurrent chemoradiotherapy with carboplatin and uracil-f tegafur (UFT) seems to be a promising and appropriate regimen for patients with poor performance status (PS) with locally advanced squamous cell carcinoma of the head and neck (SCCHN). OBJECTIVE: We designed a regimen based on divided low-dose administration to reduce toxicity for patients with poor PS with locally advanced SCCHN. PATIENTS AND METHODS: Sixty-two patients with previously untreated stage III-IV SCCHN and PS of 2 or 3 were entered into this study. They received radiotherapy: 70 Gy/35 fractions. The chemotherapy consisted of a combination of carboplatin (Calvert's formula: (GFR+25) x AUC (=5)/4 mg/week; where AUC area under the curve and GFR = glomerular filtration rate) and UFT (300 mg/day, per os). RESULTS: The overall clinical response rate and the pathological complete response (CR) were 90% (56/62) and 61% (38/62), respectively. Grade > or =3 mucositis occurred in only 6% of patients (4/62) and grade 2 > or =3 leukocytopenia and neutropenia occurred in only 5% (3/62). PMID- 17851891 TI - Expression of MCP-4 by TLR ligand-stimulated nasal polyp fibroblasts. AB - CONCLUSION: These results indicate that nasal polyp fibroblasts contribute to innate immunity and eosinophilic inflammation such as nasal polyposis. OBJECTIVE: It is generally accepted that type 2 T helper (Th2) cytokines and some chemoattractants play an essential role in the pathogenesis of nasal polyposis. Nasal polyposis is characterized by chronic eosinophilic inflammation. The mechanisms that cause the predominance of eosinophilic infiltration in nasal polyposis have yet to be clarified. There is growing evidence that fibroblasts could be a major source of Th2 chemokines. Because the nasal and paranasal mucosae are the first respiratory tissues that environmental agents encounter, those tissues are exposed to injurious agents, including microorganisms and their breakdown products. We investigated whether nasal polyp fibroblasts produce a C-C chemokine, MCP-4, when stimulated with the breakdown products of microorganisms and a Th2 cytokine (interleukin (IL)-4). MATERIALS AND METHODS: Fibroblast lines were established from nasal polyp tissues. The expression of MCP-4 mRNA was evaluated by real-time RT-PCR. The amount of MCP-4 in the supernatants was measured by ELISA. RESULTS: TLR2, 3, 4 and 5 ligands, but not TLR7/8 or 9 ligands, induced small amounts of MCP-4. TLR2, 3, 4 and 5 ligands synergized with IL-4 to induce the production of MCP-4. PMID- 17851892 TI - Speech and music perception with the new fine structure speech coding strategy: preliminary results. AB - CONCLUSIONS: Taking into account the excellent results with significant improvements in the speech tests and the very high satisfaction of the patients using the new strategy, this first implementation of a fine structure strategy could offer a new quality of hearing with cochlear implants (CIs). OBJECTIVE: This study consisted of an intra-individual comparison of speech recognition, music perception and patient preference when subjects used two different speech coding strategies with a MedEl Pulsar CI: continuous interleaved sampling (CIS) and the new fine structure processing (FSP) strategy. In contrast to envelope based strategies, the FSP strategy also delivers subtle pitch and timing differences of sound to the user and is thereby supposed to enhance speech perception in noise and increase the quality of music perception. PATIENTS AND METHODS: This was a prospective study assessing performance with two different speech coding strategies. The setting was a CI programme at an academic tertiary referral centre. Fourteen post-lingually deaf patients using a MedEl Pulsar CI with a mean CI experience of 0.98 years were supplied with the new FSP speech coding strategy. Subjects consecutively used the two different speech coding strategies. Speech and music tests were performed with the previously fitted CIS strategy, immediately after fitting with the new FSP strategy and 4, 8 and 12 weeks later. The main outcome measures were individual performance and subjective assessment of two different speech processors. RESULTS: Speech and music test scores improved statistically significantly after conversion from CIS to FSP strategy. Twelve of 14 patients preferred the new FSP speech processing strategy over the CIS strategy. PMID- 17851893 TI - Effects of inflammatory changes in the middle ear mucosa on middle ear total pressure. AB - CONCLUSIONS: Inflammation of the middle ear mucosa leads to inhibition of transmucosal carbon dioxide (CO2) diffusion. Furthermore, CO2 diffusion is inhibited more severely in ears with a histologically higher grade of inflammation. OBJECTIVES: To investigate the effect of inflammatory changes in the middle ear mucosa on transmucosal gas exchange, and the relationship between the histologic inflammation grade of the middle ear mucosa and the middle ear total pressure (METP). MATERIALS AND METHODS: Twenty-six rabbits were used for this study. Changes in the METP and the oxygen partial pressure in the middle ear (PmO2) were measured in the otitis media group and the untreated group, and were compared between the two groups. Inflammatory changes in the middle ear mucosa were classified into four grades histologically, and the relationship between the histologic inflammatory grade and the maximum METP was examined. RESULTS: The maximum METP in the otitis media group was significantly decreased compared with the untreated group (p < 0.05), but there was no difference between the two groups in the rate of decrease of the PmO2. Furthermore, the maximum METP in grade III inflammation was significantly decreased compared with that in grade II inflammation (p < 0.05). PMID- 17851894 TI - Glycoconjugate expression in perennial allergic rhinitis: a lectin histopathological study. AB - CONCLUSIONS: The data show that differences in the concentrations of glycoconjugates of patients with perennial allergic rhinitis (PAR) and normal controls are modest, thus indicating that the composition of the mucus in allergic patients largely resembles that of healthy individuals. The findings may point to the need for volume reduction methods controlling mucus production in patients with PAR. OBJECTIVES: We aimed to study the composition and concentration of inferior turbinate glycoconjugates of patients with PAR. MATERIALS AND METHODS: Six specific oligosaccharides found in the inferior turbinate mucosa were stained with a battery of 10 lectins. The samples recruited for study were 15 sections from patients with PAR and 17 from healthy individuals who had no nasal disease and underwent rhinoplasty surgery for cosmetic reasons. Both groups were matched for age (p = 0.208). Results. No significant difference in the concentration of galactose, fucose, sialic acid, N-acetylglucosamine, and N-acetylgalactosamine in the epithelium and submucosal glands of the inferior turbinate was found between the groups. Likewise, neuraminidase digestion of peripheral sialic acid revealed similar concentration of the penultimate galactose residue. The only significant difference was a higher concentration of mannose in submucosal serous glands of patients with PAR compared with normal controls (p = 0.04). PMID- 17851895 TI - Determination of lymph node micrometastases in patients with supraglottic carcinoma. AB - CONCLUSIONS: The frequency of loss of heterozygosity (LOH) at D9S 171 microsatellite locus on 9p21 may serve as an available method to evaluate occult micrometastases in laryngeal squamous cell carcinoma. High frequency of LOH was associated with a decreased probability of survival time. OBJECTIVE: To explore an available and sensitive method to detect cervical lymph node micrometastases in patients with laryngeal squamous cell carcinoma, the frequency of LOH at D9S171 microsatellite locus on 9p21 was studied. PATIENTS AND METHODS: Twenty samples from supraglottic cancer and 182 lymph nodes from neck dissections were examined by LOH comparing immunohistochemical (IHC) staining using cytokeratin 19 (CK19), and hematoxylin and eosin (H&E) staining. The frequency of lymph node metastasis and the clinical relevance were analysed. RESULTS: The frequency of LOH was 37.4% of lymph nodes and all of the primary tumors. Occult micrometastases were present in 9 of 20 cases; 23.6% of lymph nodes were positive for CK19 by IHC; 16.5% of lymph nodes were positive by H&E. There was a highly significant difference among the three methods. The highest rate of positive lymph nodes was at level II of the neck. There was a highly significant difference between overall survival time and lymph node metastasis with LOH and CK19 analysis. PMID- 17851896 TI - Meniett therapy may avoid vestibular neurectomy in disabling Meniere's disease. AB - CONCLUSION: In those patients for whom vestibular neurectomy has been selected due to the disabling recurrence of vertigo spells, Meniett therapy has been shown to allow avoidance of this surgical procedure in a fairly high percentage of patients with Meniere's disease (MD). Our data would also support a better result when pressure treatment is acting on MD of short duration. OBJECTIVE: To test the possibility that low pressure treatment (Meniett) could avoid vestibular neurectomy in patients with MD that was refractory to medical treatment. PATIENTS AND METHODS: The setting was a tertiary referral centre in a university hospital. Thirty-six MD patients, for whom vestibular neurectomy was indicated, underwent Meniett treatment and composed a group in which a long-term (>2 years) follow-up was achieved. Additionally, different durations of MD ('young' and 'old' MD) were distinguished and analysed separately. RESULTS: Twenty-five patients (69.4%) were treated satisfactorily by using Meniett treatment and therefore avoided vestibular neurectomy. In half of them only one cycle of treatment was necessary. PMID- 17851897 TI - FDG-PET interpretation in tonsillar lymphoma. PMID- 17851898 TI - Mapping of Ki-67 protein distribution on whole organ serial sections of the larynx. AB - CONCLUSIONS: Immunostaining of whole organ serial sections of the larynx is feasible and will allow analysis of cellular alterations in the undisturbed anatomical context of whole organ serial sections of the larynx. OBJECTIVES: Whole organ serial sections of the larynx have to date been used for conventional macroscopic evaluation of laryngeal tissues. The aim of this study was to establish a protocol for immunohistochemistry of whole organ sections of the larynx. MATERIALS AND METHODS: Five laryngectomy specimens were obtained during surgery for advanced laryngeal carcinoma. Using a novel method for paraffin embedding, we chose the proliferation marker Ki-67 antigen as a model target for immunoreactivity on serial sections. RESULTS: We were able to produce whole organ serial sections that could then be immunostained for Ki-67. A complete mapping of proliferating cells throughout the tumour, at the tumour front and in skip lesions was subsequently obtained. PMID- 17851899 TI - Connectivity can be used to identify key genes in DNA microarray data: a study based on gene expression in nasal polyps before and after treatment with glucocorticoids. AB - CONCLUSIONS: The presented analysis of nasal polyposis using connectivity based on the PubGene literature co-citation network demonstrates that this tool can be used to identify key genes in DNA microarray studies of human polygenic diseases. OBJECTIVES: DNA microarray studies of complex diseases may reveal differential expression of hundreds of genes. According to network theory and studies of yeast cells, genes that are connected with several other genes appear to have key regulatory roles. This study aimed to examine if this principle can be translated to DNA microarray studies of human disease, using nasal polyposis as a base for the analysis. MATERIALS AND METHODS: The connectivity of differentially expressed genes from a previously described microarray study of nasal polyposis before and after treatment with glucocorticoids was determined. This was done using the literature co-citation network PubGene. RESULTS: In all, 166 genes were differentially expressed; 39 of these were previously defined as inflammatory and considered important for nasal polyposis. The connectivity of all differentially expressed genes was analysed using the PubGene literature co-citation network. Seventy-four of the 166 genes were connected to other genes. By contrast, the average number of connected genes among 100 sets of 166 randomly chosen genes was 31.5. A small number of the differentially expressed genes were highly connected, while most genes had few or no connections. This indicated a scale-free network. The most connected gene was interleukin-8, an inflammatory gene of known importance for nasal polyposis. Twenty-eight of the 74 connected genes were inflammatory (38%), compared with 11 of the 92 unconnected genes (12%), p < 0.0001. Since most evidence suggests that nasal polyps are inflammatory in their nature, this supports the hypothesis that connected genes have more disease relevance than unconnected genes. PMID- 17851900 TI - Changes in the audiograms of a nasopharyngeal cancer patient during the course of treatment: a temporal bone histopathological study. AB - This report shows the changes that occurred in consecutive audiograms of a patient who underwent chemotherapy and radiotherapy for nasopharyngeal cancer and the histopathological examination of the temporal bones. Both conductive and sensorineural hearing loss developed, but followed different modes of progression. In the left ear, an air-bone gap appeared and deepened, while in the right ear, severe conductive hearing loss was present upon admission and improved after treatment. Sensorineural hearing loss was worse in the right ear, but deteriorated gradually in both ears. Histology revealed tumor invasion in the right temporal bone. Both middle ears showed effusion, but no radiation-induced changes that may be responsible for the conductive loss. The main changes in the cochlea were vascular stria degeneration, spiral ligament atrophy, and spiral ganglion cell depletion, while the hair cells were only occasionally missing. Apart from confirming what has been established previously by other authors, some interesting findings were observed: (1) in addition to the high frequency hearing loss typically caused by cis-platinum and by radiation, there was also low frequency hearing loss, and (2) the cochlear damage was most severe in the vascular stria and spiral ganglions, sparing the hair cells. PMID- 17851901 TI - Habitual sniffing and postoperative configuration of the posterior meatal wall reconstructed with soft tissue. AB - CONCLUSIONS: Habitual sniffing is a significant contributing factor to the development of postoperative retraction of the reconstructed posterior meatal wall and tympanic membrane, although it still seems a multifactorial event. OBJECTIVE: To examine the possible contribution of habitual sniffing to retraction-type middle ear pathology in a more direct way than previous reports. PATIENTS AND METHODS: The correlation between habitual sniffing and the postoperative configuration of the posterior meatal wall was examined in 58 patients with cholesteatoma who underwent tympanoplasty with reconstruction of the soft meatal wall. RESULTS: The postoperative configuration of the posterior meatal wall showed severe retraction in 7 of 8 patients with habitual sniffing, but only 22 of 47 without habitual sniffing. Habitual sniffing was significantly associated with postoperative severe retraction (Fisher's exact test, p<0.05). PMID- 17851902 TI - Hippocampal volume measurement in patients with Meniere's disease: a pilot study. AB - CONCLUSION: No signs of chronic stress as in hippocampal atrophy were present in patients with Meniere's disease. OBJECTIVE: To evaluate the effect of chronic stress (allostatic load) by measuring hippocampal volume in patients with Meniere's disease. SUBJECTS AND METHODS: Ten patients with Meniere's disease and 10 healthy controls were evaluated for absolute and relative hippocampal volumes measured on MRI scans, saliva cortisol levels and frequency of daily stressors. The study was performed in a prospective, controlled setting with two raters who were blinded as to subject identity. RESULTS: Saliva cortisol levels and presence of daily stressor scores were similar in both groups. The first rater measured mean hippocampal volumes of 2.80 +/- 0.36 cm3 vs 3.15 +/- 0.52 cm3 (right) and 2.49 +/- 0.32 cm3 vs 3.06 +/- 0.46 cm3 (left), for the Meniere's disease and control group, respectively. The second rater measured 3.44 +/- 0.35 cm3 vs 3.60 +/- 0.52 cm3 (right) and 3.00 +/- 0.40 cm3 vs 3.42 +/- 0.45 cm3 (left), respectively. The volume of the left hippocampus was significantly smaller in patients with Meniere's disease compared with the controls for both raters (p < 0.05) and the right hippocampal volume was not different between the two groups. With correction for variation in head size (partial brain and partial intracranial volume) no significant differences in relative hippocampal volumes were observed between patients with Meniere's disease and the control group. PMID- 17851903 TI - Prognostic significance of DNA cytometry in combination with AgNOR investigation. AB - CONCLUSION: While most results concerning DNA and nucleolar organizer region (AgNOR) parameters fit with previous studies, the percentage of aneuploidy looks like a promising prognostic parameter. The observed intratumoral heterogeneity could represent a possible source of conflicting and inconsistent results. OBJECTIVES: The aims of our study were to determine the prognostic relevance of different DNA and AgNOR parameters in laryngeal squamous cell carcinoma (SCC) and compare these findings with established prognostic factors including tumor stage and grade, as well as the detection of possible intratumoral heterogeneity. MATERIALS AND METHODS: Sections from 62 laryngeal SCCs were analyzed for DNA content, DNA index, S-phase, percentage of aneuploidy, and AgNOR. Of 62 samples, 31 morphologically similar tumor samples were analyzed for the same parameters in three different tumor areas defined as tumor center, invasive tumor margin, and transformation margin between tumor and normal-appearing mucosa. RESULTS: Our study showed that DNA and AgNOR parameters correlated with T stage, lymph node involvement, and histologic grade regardless of tumor areas. Significant correlation was found between mean number of AgNOR per nucleus and percentage of aneuploidy. Clinical stage and percentage of aneuploidy correlated with survival (p<0.02). Heterogeneity DNA study revealed aneuploidy in central portions of 90% of tumors, while in margins aneuploidy was demonstrated in about half of the patients. PMID- 17851904 TI - Is dissection of levels 4 and 5 justified for cN0 laryngeal and hypopharyngeal cancer? AB - CONCLUSION: Dissecting levels 2 and 3 and sparing the dissection of level 4 and the contralateral neck when frozen section results are negative are reasonable options for the selective dissection of cN0 necks. Our findings show that dissection of level 5 is considered unnecessary, unless there is overt metastasis. OBJECTIVE: The level of node involvement and recurrence rates were assessed in cN0 laryngeal and hypopharyngeal carcinoma patients in order to develop appropriate guidelines for the treatment of the neck. MATERIALS AND METHODS: A total of 328 cN0 necks operated with selective dissection were reviewed retrospectively. Patients were monitored for at least 24 months and regional recurrences were evaluated. RESULTS: The prevalence of level 4 occult metastases was 3.4%; 1.5% of them were isolated to level 4. We observed regional recurrence in 5.6% of the necks. No case of metastasis or regional relapse was observed in level 5. PMID- 17851905 TI - Carbamazepine reduces the behavioural manifestations of tinnitus following salicylate treatment in rats. AB - CONCLUSION: The results are consistent with the hypothesis that carbarmazepine (CBZ) has efficacy against tinnitus in humans. OBJECTIVE: CBZ is an anti epileptic drug that is widely used for the treatment of tinnitus. Despite this, there are relatively few clinical trials or preclinical studies supporting its efficacy. In an effort to increase the amount of information available on CBZ, the aim of this study was to investigate the efficacy of CBZ in salicylate induced tinnitus in rats MATERIALS AND METHODS: We investigated the effects of CBZ in an animal model of tinnitus induced by the injection of salicylate using a conditioned lick suppression paradigm. RESULTS: We found that CBZ, at a dose of 15 mg/kg i.p., but not at 5 mg/kg or 30 mg/ kg, significantly suppressed the behavioural manifestations of tinnitus. PMID- 17851906 TI - Differential diagnosis of true and pseudo-bilateral benign positional nystagmus. AB - CONCLUSIONS: Two patients showing two rotational axes of their positional nystagmus had canalolithiasis in bilateral posterior semicircular canals (PSCCs), leading to the diagnosis of true bilateral benign paroxysmal positional nystagmus (P-BPPN). Another 18 patients had a single rotation axis of their positional nystagmus with short time constant (TC) on one side and long TC on the other. Since canalolithiasis in the uppermost PSCC may be transient cupulolithiasis, evoking positional nystagmus with long TC, the diagnosis of the latter patients should be pseudo-bilateral P-BPPN. OBJECTIVE: To differentiate the true bilateral posterior canal type of P-BPPN from pseudo-bilateral P-BPPN. PATIENTS AND METHODS: The rotational axis and TC of positional nystagmus were three dimensionally analyzed in 20 patients showing geotropic torsional nystagmus on the left and right Dix-Hallpike (D-H) maneuvers. RESULTS: Two patients showed two rotational axes of their positional nystagmus, which were perpendicular to the plane of the PSCCs. There were no differences in TCs of their positional nystagmus between bilateral D-Hs. Another 18 patients showed a single rotational axis of their positional nystagmus, which was perpendicular to the plane of either the left or right PSCC. TCs of their positional nystagmus were short on one side and long on the other. PMID- 17851907 TI - Pressure equilibration in the penguin middle ear. AB - CONCLUSIONS: King penguins have a venous structure in the form of a corpus cavernosum (CC) in their middle ear (ME) submucosa. The CC may be viewed as a special organelle that can change ME volume for pressure equilibration during deep-sea diving it is a pressure regulating organelle (PRO). A similar CC and muscles also surround the external ear (EE) and may constrict it, isolating the tympanic membrane from the outside. A CC was previously found also in the ME of marine diving mammals and can be expected to exist in other deep diving animals, such as marine turtles. OBJECTIVES: Marine animals require equalization of middle ear (ME) pressure when diving hundreds or thousands of meters to catch prey. We investigated what mechanism enables king penguins to protect their ME when they dive to great depths. MATERIALS AND METHODS: Biopsies and serial sections of the ME and the EE of the deep diving king penguin (Aptenodytes patagonicus) were examined microscopically. RESULTS: It was demonstrated that the penguin ME has an extensive network of small and large submucosal venous sinuses. This venous formation, a corpus cavernosum, can expand and potentially 'flood' the ME almost completely on diving, thus elevating ME pressure and reducing the ME space. The EE has a similar protective mechanism. PMID- 17851908 TI - Middle ear mucosa regeneration by grafting of artificial mucosa. AB - CONCLUSION: Artificial middle ear mucosa (AMEM), a sheet of mucosal cells grown on collagen gel populated with fibroblasts, is useful as graft material that is able to promote mucosal regeneration after middle ear surgery. OBJECTIVES: Regeneration of the middle ear mucosa and pneumatization of the mastoid cavity is critical for good prognosis. We examined whether implantation of AMEM into damaged middle ear cavity would promote mucosal regeneration. MATERIALS AND METHODS: AMEM was prepared as described previously using epithelial cells and fibroblasts isolated from the rabbit middle ear. We implanted AMEM into rabbit middle ear from which mucosa had been surgically removed and evaluated its histological and functional recovery 8 weeks later. Three other groups were used for comparison: a normal control group, a mucosa-eliminated group, and a collagen implanted group. RESULTS: AMEM grew to be morphologically similar to the native middle ear mucosa. Electron microscope studies showed that implanted AMEM has basal lamina and cilia. AMEM implantation suppressed bone hyperplasia and granulation, leading to better mucosal regeneration. Mucosal gas exchange was also significantly improved after implantation. PMID- 17851909 TI - Cochlear modiolus and lateral semicircular canal in sudden deafness. AB - CONCLUSION: This study demonstrated that precise analysis shows that the inner ear shape in sudden deafness (SD) is different from that in controls in that the fluid-filled area of SD labyrinths is significantly larger than that of controls. Reduced cochlear modiolus area and inner area of the lateral semicircular canal (LSCC) may be associated with insufficient maturation of the inner ear. OBJECTIVE: The aim of this study was to quantify the morphologies of the cochlea and LSCC using magnetic resonance imaging (MRI) and to evaluate their relationships with clinical symptoms in SD. SUBJECTS AND METHODS: Twenty-six unilateral SD patients with vertigo, 26 unilateral SD patients without vertigo and a matched control group without hearing loss were studied. The areas of cochlear modioli and LSCCs were traced on the MRI console and compared between SD patients with or without vertigo and control subjects. The ratio of the LSCC fluid-filled area to the total LSCC area was used to index the degree of dysplasia. RESULTS: The cochlear modiolus area was significantly less in SD ears (4.1+/-0.2 mm2) than in controls (4.3+/-0.4 mm2). The LSCC inner area was significantly less in SD ears (6.9+/-1.7 mm2) than in controls (9.1+/-1.8 mm2). These results suggest that the fluid-filled area of SD labyrinths is significantly larger than controls. Morphology did not differ between affected and contralateral sides or between ears with or without vertigo in SD patients. PMID- 17851910 TI - Effect of acute endolymphatic hydrops overload on the endolymphatic sac. AB - CONCLUSIONS: Homeostasis of endolymph volume is a complex mechanism, in which the endolymphatic sac (ES) may play an important role. OBJECTIVES: To elucidate the effect of acute endolymphatic hydrops (EH) on the ES and to gain further information about the volume and pressure regulative function of the ES. MATERIALS AND METHODS: Distilled water was injected into the middle ear cavity of adult CBA/J mice. The ESs were studied morphologically by light and transmission electron microscopy. RESULTS: Mild EH was found, particularly in the upper turn of the cochlea. Acute EH led to an increase in the size of the ES lumen, accompanied by collapse of the lateral intercellular spaces and dense perisaccular tissue, changes which had reversed 2 h after the injection. PMID- 17851911 TI - Dexamethasone and methylprednisolone do not inhibit neuritic outgrowth while inhibiting outgrowth of fibroblasts from spiral ganglion explants. AB - CONCLUSION: Dexamethasone and methylprednisolone do not inhibit neuritic outgrowth while inhibiting fibroblastic outgrowth from spiral ganglion micro explants. OBJECTIVES: To demonstrate reduced fibroblastic outgrowth while maintaining neurite outgrowth for several corticosteroids using an in vitro test system of neonatal rat spiral ganglion micro-explants. MATERIALS AND METHODS: The in vitro test system comprised 3-day-old rat spiral ganglion micro-explants. Dexamethasone, methylprednisolone, triamcinolone acetonide, and human recombinant brain-derived neurotrophic factor (hrBDNF) were tested in vitro. The control was ganglion micro-explants in supplemented Dulbecco's modified Eagle's medium. Areas of the ganglion explant, neurite and fibroblast outgrowth of ganglion explants after 10 days in vitro were imaged, digitized, and analyzed using Image Tool 3.00 on a PC workstation. Areas of neurite and fibroblast outgrowth from the experimental explants were compared against values obtained from control explants. RESULTS: Dexamethasone gave the best result of the three corticosteroids tested for inhibiting fibroblast outgrowth while not inhibiting neurite outgrowth from the ganglion micro-explants. Media containing hrBDNF (10 ng/ml) stimulated significantly greater neurite outgrowth than outgrowth from control explants (p < 0.001). Ganglion micro-explants treated with dexamethasone (0.02 mg/ml) and methylprednisolone (0.5 mg/ml) provided the greatest inhibition of fibroblast outgrowth compared with control explants (p < 0.001). PMID- 17851912 TI - Simultaneous bilateral stapes surgery--a pilot study. AB - CONCLUSIONS: The short-term postoperative results of bilateral stapes surgery were satisfactory. Hearing results between the two ears were comparable and there was no increased complication risk for the second ear. The results are encouraging, although a larger series and longer follow-up time are needed to confirm them. OBJECTIVE: The purpose of our study was to evaluate the preliminary outcome of simultaneous bilateral stapes operation. PATIENTS AND METHODS: Eight patients suffering from bilateral otosclerosis and one from osteogenesis imperfecta were prospectively included in the pilot study. Both ears were operated under general anesthesia by the same surgeon. Inclusion criteria were mean conductive hearing loss of 15 dB or more at frequencies 0.5-4.0 kHz and negative Rinne fork test (256 Hz) on both sides. Patients with mean thresholds for sensorineural hearing over 40 dB or other otoneurological diseases or medications were excluded. Pure tone audiogram was performed 3 months after the operation. RESULTS: The air-bone gap diminished from 28 (range 19-41) to 10 (range 4-23) dB in the first ear and from 24 (range 16-40) to 8 (range 3-19) dB in the second. Four patients experienced mild, temporary dizziness during rapid head movements, but that resolved fully. No patient suffered significant sensorineural hearing loss. PMID- 17851913 TI - The clinical utility of search coil horizontal vestibulo-ocular reflex testing. AB - CONCLUSION: Testing of the horizontal vestibulo-ocular reflex (VOR) with head rotations (including head impulses) using the magnetic scleral search coil technique (SCT HHI) provides valuable additional diagnostic information in patients with persistent dizziness, oscillopsia or imbalance. It identifies high and low frequency/acceleration vestibular abnormalities that are frequently missed using other methods. OBJECTIVES: To evaluate the diagnostic utility of SCT measurement of the horizontal VOR in the multidisciplinary neurotology clinic of a tertiary referral centre. PATIENTS AND METHODS: The records of 127 consecutive patients referred for persistent dizziness, oscillopsia, imbalance, or with clinical findings suggestive of high frequency/acceleration vestibular dysfunction were reviewed. All had been tested with clinical head impulses, bithermal calorics and vestibular-evoked myogenic potentials. VOR gain (peak eye velocity/peak head velocity) had been measured both in response to sinusoidal oscillations in a rotating chair (0.1-11 Hz) and to manually delivered horizontal head rotations (peak head velocities 50-500 degrees/s) using SCT. RESULTS: Agreement between the different test modalities of horizontal semicircular canal function was moderate. Relative to SCT HHI, clinical HHI showed the highest sensitivity and the lowest specificity (both 70%). SCT HHI appeared to have the greatest diagnostic yield, when compared with calorics and SCT ROT (23% of all abnormalities shown were detected only by SCT HHI) and also allowed detection of significant asymmetries in patients with bilateral vestibular dysfunction. PMID- 17851914 TI - Changes in slow phase eye velocity and time constant of positional nystagmus at transform from cupulolithiasis to canalolithiasis. AB - Changes in slow phase eye velocity (SPEV) and time constant (TC) of benign paroxysmal positional nystagmus in horizontal canal type were examined at transitional period from cupulolithiasis (apogeotropic nystagmus) into canalolithiasis (geotropic nystagmus) in two patients. SPEV and TC of positional nystagmus were tri-dimensionally analyzed. The first patient showed an apogeotropic nystagmus. Head rotation to the left in supine position induced a right-beating nystagmus with an initial SPEVof 15.3 degrees/s and a TC of 133 s. The nystagmus then gradually declined with a TC of 31.3 s after reaching a maximum SPEV of 28.8 degrees/s. After the nystagmus disappeared, he showed a geotropic nystagmus. The second patient showed a left-beating nystagmus with an initial SPEV of 2.5 degrees/s and a TC of 141 s when his head was rotated to the right in supine position. The nystagmus then gradually declined with a TC of 8.05 s after reaching a maximum SPEV of 16.7 degrees/s. After the nystagmus disappeared, he showed a geotropic nystagmus. The present findings suggested that in both patients, at the period of an increase of SPEV of the positional nystagmus with the shortening of its TC, cupulolithiasis transformed into canalolithiasis. PMID- 17851915 TI - Expression of epidermal growth factor receptor, transforming growth factor-alpha and Ki-67 in relationship to malignant transformation of pleomorphic adenoma. AB - CONCLUSION: Quantitative assessment is more sensitive as a measure of cellular protein content as compared with standard optical density measurements. The data support the hypothesis that increased epidermal growth factor receptor (EGFR) and transforming growth factor (TGF)-alpha expression is associated with early events in malignant transformation of pleomorphic adenoma (PA). OBJECTIVE: In the present study, we attempted to identify EGFR and TGF-alpha expression and Ki-67 index in carcinoma ex-pleomorphic adenoma (Ca ex-PA) and PA. We also compared the presence of EGFR and TGF-alpha and Ki-67 index with clinical data. MATERIALS AND METHODS: The tissues were stained with monoclonal antibodies to EGFR, TGF-alpha and Ki-67. The results were analysed using quantitative immunohistochemical analysis. We also analysed the association of patients' prognosis with clinical parameters and the histological classification of the carcinomatous component. RESULTS: As regards the association of patients' prognosis with EGFR staining and Ki-67 index, a significant increase was observed in patients who died or had residual disease compared with patients who were alive without disease. In the immunohistochemical analysis of EGFR and TGF-alpha and Ki67 index, a significant increase was observed in Ca ex-PA, especially with adenocarcinoma, compared with PA and sialadenitis. PMID- 17851916 TI - Therapeutic effectiveness over time of intratympanic dexamethasone as salvage treatment of sudden deafness. AB - CONCLUSION: Intratympanic dexamethasone (ITD) within 1 month after initial treatment failure should be utilized as salvage treatment for refractory sudden sensorineural hearing loss (SSNHL). OBJECTIVE: To investigate the therapeutic efficacy over time of ITD as salvage treatment in SSNHL. MATERIALS AND METHODS: We retrospectively reviewed the medical records and audiograms of 99 SSNHL patients who were refractory to 2 weeks of oral steroid treatment, from August 2003 to October 2006. Patients were divided into those receiving no further treatment (control group) and those receiving ITD within 2 weeks (early-ITD), between 2 weeks and 1 month (mid-ITD), and between 1 and 2 months (late-ITD) after initial treatment failure. ITD was performed in the supine position on four separate occasions over the course of 2 weeks. Final assessment of hearing was carried out 3 months after outbreak of SSNHL. Hearing improvement was defined as a > 15 dB decrease in four-tone average (FTA). RESULTS: Overall hearing improvement was observed in 8 of 50 (16.0%) control patients, 7 of 16 (43.8%) early ITD patients, 6 of 20 (30.0%) mid ITD patients, and 2 of 13 (15.4%) late ITD patients. PMID- 17851917 TI - Influence of allergy in patients with nasal polyposis after endoscopic sinus surgery. AB - CONCLUSION: Allergy does not modify the symptoms and steroid consumption (oral and local) of nasal polyposis (NP) patients after functional endoscopic sinus surgery (FESS). OBJECTIVES: To assess the role of allergy in the evolution after FESS of patients presenting with the diagnosis of NP. PATIENTS AND METHODS: This was a prospective study of 63 consecutive patients with NP (57% males, mean age 45.8 years), who were analyzed to detect whether the results of a surgical treatment of NP were influenced by the presence of positive allergic tests (Phadiatop). Three nasal criteria were scored: nasal obstruction, posterior rhinorrhea, and the loss of smell. The frequency of asthma was evaluated. Medical treatment of NP after FESS consisted of washing of the nasal cavities, steroid spray, and oral steroid administration. The amount of consumption of steroids (prednisolone and beclomethasone) was studied. RESULTS: Decrease of all nasal symptoms was not statistically different in the two groups of patients with and without allergy. Cumulative consumption of prednisolone and beclomethasone after surgery was similar in the two groups. PMID- 17851918 TI - Nystagmus induced by high frequency vibrations of the skull in total unilateral peripheral vestibular lesions. AB - CONCLUSION: The skull vibration-induced nystagmus test (SVINT) is a useful complementary test to the caloric test, which evaluates very low frequencies, and the head shaking test (HST), which explores medium range frequencies. These three tests are fully correlated in total unilateral vestibular lesions (tUVL) with a sensitivity of 98% and a specificity of 94% for the SVINT. The results of the interference of the SVINT with the cold caloric test on the intact ear suggest that different vestibular sensory cells are involved in these two tests. The stimulus location optimization suggests that vibrations directly stimulate the inner ear on the intact side. OBJECTIVES: The aim of this study was to establish the effectiveness of a rapid, non-invasive test used to detect vestibular asymmetry at 30, 60 and 100 Hz stimulation in tUVL. PATIENTS AND METHODS: The high frequency vibration test applied to the skull using the SVINT was compared to the results of HST and caloric test in 134 patients and 95 normal subjects: 131 patients had a total unilateral vestibular dysfunction and 3 had a bilateral total lesion (tBVL). The effects of stimulus frequency, topography and head position were studied using a video-nystagmograph. RESULTS: In tUVL, the SVINT always revealed a lesional nystagmus beating toward the healthy side at all frequencies. The mastoid site was more efficient than the cervical and vertex sites (p0.005). The mean skull vibratory nystagmus (SVN) slow phase velocity (SPV) is 10.7 degrees (SD =7.5; n=20). Mastoid stimulation efficiency was not correlated with the side of stimulation. SVN SPV was correlated with the total caloric efficiency on the healthy ear (p=0.03). The interference of the SVINT during the cold caloric test on the intact ear demonstrated a reversal of the caloric nystagmus at each application of the vibrator. In tBVL, SVINT revealed no nystagmus. PMID- 17851919 TI - Protective effect of edaravone against endolymphatic hydrops. AB - CONCLUSION: Our findings suggest that edaravone prevented the production of reactive oxygen species (ROS). Edaravone also delayed the formation of endolymphatic hydrops in guinea pigs, but had no effect on endolymphatic hydrops. OBJECTIVE: To analyse the protective effect of a free radical scavenger, edaravone, on endolymphatic hydrops. MATERIALS AND METHODS: Guinea pigs were subjected to surgical obliteration of the endolymphatic duct (ED). For the detection of ROS, group 1 received intraperitoneal injections of edaravone (3 mg/kg/day) for 2 days, group 2 received edaravone for 2 weeks, group 3 saline for 2 days, and group 4 saline for 2 weeks. ROS production by the organ of Corti and stria vascularis was examined by using dihydrotetramethylrosamine. For the morphological analysis, guinea pigs were divided into five groups, i.e. 2 or 4 weeks after ED obliteration, 2 weeks with edaravone, first or last 2 weeks with edaravone and sacrificed 4 weeks after ED obliteration. Increases in the ratios of the cross-sectional area of scala media were analysed quantitatively to assess the degree of endolymphatic hydrops among the above-mentioned five groups of the hydropic cochlea. RESULTS: ROS was detected both in the organ of Corti and in the lateral wall of cochleae 2 days after ED obliteration. Edaravone prevented the production of ROS and also attenuated the formation of endolymphatic hydrops in the acute hydrops group. PMID- 17851920 TI - Sentinel lymph node biopsy as an alternative to wait and see policy in patients with small T1 oral cavity squamous cell carcinoma. AB - CONCLUSION: Although sentinel lymph node (SLN) biopsy is not yet validated for clinical use to replace elective neck dissection in patients with oral squamous cell carcinoma, it can be recommended for patients who do not fulfil the criteria for elective neck treatment according to current treatment protocols. OBJECTIVE: To examine the benefits of SLN biopsy in oral cancer patients who have a small risk for occult metastasis and therefore are not considered candidates for elective neck treatment. PATIENTS AND METHODS: Thirteen consecutive patients with a small T1 oral cavity squamous cell carcinoma, clinically staged NO, and who did not meet the indications for elective neck treatment, underwent SLN biopsy. The SLNs were cut at 1-2 mm intervals and stained with haematoxylin and eosin and cytokeratin AE1/AE3. RESULTS: Histopathological examination of SLNs revealed micrometastases in two patients. A selective neck dissection was performed on these patients and no further metastases were encountered. All patients had a minimum follow-up of 12 months and no cervical or other recurrences were encountered. PMID- 17851921 TI - Evaluation of brainstem function in patients with spasmodic dysphonia using vestibular evoked myogenic potentials and auditory brainstem responses. AB - CONCLUSION: The vestibular area is closer than the auditory region to nucleus ambiguus. If a 'shared' lesion involves regions of adjacent nuclei of the brainstem in patients with spasmodic dysphonia then vestibular area involvement is more possible than that of the auditory region. OBJECTIVES: The authors hypothesize that lower brainstem lesions and involvement of descending pathways of the spinal tract may be the site of lesion in patients with spasmodic dysphonia. PATIENTS AND METHODS: Ten patients with spasmodic dysphonia were tested using the auditory brainstem response (ABR) and vestibular evoked myogenic potentials (VEMPs). RESULTS: No ABR abnormalities were found in right ears. Results of ABR on the left ear showed that one patient had abnormal ABR. This patient had severe sensorineural hearing loss on the left side. VEMPs displayed normal response in two patients bilaterally. First positive (p13) and second negative (n23) waves of VEMP could not be recorded in three cases unilaterally and in five patients bilaterally. PMID- 17851922 TI - Clinical significance of vertical component of caloric response including its second phase in vertiginous patients. AB - CONCLUSIONS: Up-beating vertical component recorded in the caloric first phase was attributed mainly to the inhibitory endolymph flow in the anterior canal. Down-beating vertical component recorded in the caloric second phase provoked by a positional change could be explained by a reversed endolymph flow in vertical canal(s). OBJECTIVE: To investigate the origin of a vertical component in caloric response. MATERIALS AND METHODS: We analyzed electronystagmography (ENG) of caloric responses, which had measurable horizontal component in the caloric first phase in both ears in 200 ears of 100 vertiginous patients. A caloric first phase was provoked by cold water in the supine position with the lateral semicircular canal earth-vertical. A caloric second phase was provoked by re-orienting the lateral canal from the earth-vertical to earth-horizontal after the cessation of the first phase (provoked second phase). The nystagmus of the whole procedure was recorded by two-dimensional ENG. RESULTS: We recorded the vertical component in 103/200 ears in the caloric first phase, which was directed mostly upward (92/103 ears). We also recorded the vertical component in 91/200 ears in the provoked second phase, which was directed almost exclusively downward (90/91 ears). PMID- 17851923 TI - Laryngeal myxoma. AB - Myxoma is a rare benign tumor, and occurs most commonly in the mandible and maxilla in the head and neck region. Myxoma of the larynx is extremely rare and is frequently misdiagnosed as a vocal polyp. We present the first female case of myxoma on a vocal cord and review the literature on this subject. The patient was 74 years old. She had undergone laryngomicrosurgery for a vocal cord polyp 20 years previously, but did not know the histological diagnosis. We performed laryngomicrosurgery for bilateral edematous vocal cords. Microscopic laryngoscopy demonstrated a mass in the submucosal space of the right vocal cord. The pathologic diagnosis of the mass was myxoma. Myxoma is a connective tissue tumor composed of multinucleate stellate cells suspended in an edematous, mucopolysaccharide-rich stroma. Since myxomas may infiltrate surrounding tissue, they have a high incidence of local recurrence. To prevent recurrence, myxoma should be surgically excised with surrounding normal tissue. Although no local recurrence has been detected, as myxoma is characterized by a slow growth rate, long-term follow-up is needed in this case. PMID- 17851924 TI - Complications following cochlear implantation in patients with anomalous inner ears: experiences in Asan Medical Center. AB - CONCLUSION: Although the rate of postoperative complications was higher in patients with anomalous inner ears than in patients with normal inner ears, most were minor and could be managed conservatively. These findings suggest that cochlear implantation (CI) is safe even for patients with anomalous inner ears in experienced hospitals. OBJECTIVE: To report complications encountered in patients with various types of anomalous inner ears undergoing CI in Asan Medical Center. PATIENTS AND METHODS: We retrospectively analyzed 388 patients who underwent CI between April 1999 and July 2006; of these, 80 patients had various inner ear anomalies. Immediate complications were defined as those occurring within 1 week of implantation and delayed complications as those occurring after 1 week. Minor and major complications were defined by severity requiring further management. RESULTS: Of the 80 patients with anomalous inner ears, 20 cases (25.0%) had postoperative complications, including 5 (6.3%) with major complications: facial nerve palsy, recurrent meningitis, device failure, and cerebrospinal fluid (CSF) leakage. Re-implantations were performed in three patients (3.8%). PMID- 17851925 TI - Induction of inducible nitric oxide synthase and apoptosis by LPS and TNF-alpha in nasal microvascular endothelial cells. AB - CONCLUSION: This study demonstrates that the co-administration of lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) (LPS/TNF alpha) can induce the expression of inducible nitric oxide synthase (iNOS), which results in the generation of apoptosis in cultured human nasal microvascular endothelial cells (HNMECs). Since LPS and TNF-alpha have been suggested to play an important role in the pathophysiology of nasal disease, we conclude that microvascular leakage may therefore contribute to the inflammatory process in nasal disease, such as allergic rhinitis and asthma. MATERIALS AND METHODS: The HNMECs were obtained from the inferior turbinate and subsequently cultured. The expression of iNOS induced by both the LPS and TNF-alpha was investigated by fluorescent immunohistochemistry, using confocal laser microscopy. The DNA binding dye, Hoechist 33342, was also used to analyze the apoptosis in the HNMECs. RESULTS: The fluorescent immunohistochemistory study demonstrated that LPS and TNF-alpha induced the expression of iNOS in HNMECs. LPS/TNF-alpha remarkably augmented the expression of iNOS in HNMECs in comparison to stimulation by either LPS or TNF-alpha alone. LPS/TNF-alpha also induced apoptosis in HNMECs. 1400W, a highly selective inhibitor of iNOS, inhibited both the expression of iNOS and the apoptosis induced by LPS/TNF-alpha. PMID- 17851926 TI - Benign paroxysmal positional vertigo: a series of eight singular neurectomies. AB - CONCLUSION: The singular neurectomy as described by Gacek in 1974 is an efficient procedure to control symptoms in case of intractable benign paroxysmal positional vertigo (BPPV), with an acceptable risk of postoperative sensorineural hearing loss (SNHL). We postulate that this complication may not be a direct consequence of the surgical procedure but rather may be consecutive to the reactivation of the biological phenomenon that caused the BPPV. We also observed in one patient that BPPV may exist although no nystagmus can be elicited by provocative manoeuvres. OBJECTIVE: To report our experience of the surgery, and to analyse the rate and causes of complications. PATIENTS AND METHODS: The eight patients operated in the department between August 1997 and April 2006 were evaluated in June 2006. One had been operated because he had a typical history of BPPV, but no nystagmus could be elicited by the Hallpike's manoeuvre. RESULTS: All patients were free of vertigo and considered their quality of life improved. The Hallpike's manoeuvre was negative in all cases. A SNHL occurred in two patients, immediately after surgery in one and several months later in the second. The patient with a negative Hallpike's manoeuvre before surgery went back to work 3 weeks after surgery. PMID- 17851928 TI - Postoperative results of simple underlay myringoplasty in better hearing ears. AB - CONCLUSIONS: Simple underlay myringoplasty with fibrin glue (SUM) is indicated for repair of tympanic membrane (TM) perforation in the better hearing ear because postoperative hearing deterioration is extremely rare. OBJECTIVE: To evaluate the postoperative results, including the hearing and the re-perforation rate, in the better hearing ear. MATERIALS AND METHODS: The procedure of SUM is removal of the perforation edge and bonding of the graft to the remnant TM with a few drops of fibrin glue by underlay technique. This method was applied to 75 patients with a perforated TM in the better hearing ear. The postoperative hearing and the re-perforation rate were investigated. RESULTS: The mean of the postoperative hearing gain was 10.3 dB and no cases of postoperative hearing loss were observed. Although postoperative re-perforation was found in 18 cases (24.0%), the re-perforation was closed in 16 of these cases in the outpatient department by the same procedure using frozen autologous tissue that had been harvested previously in surgery. Including these cases, the total success rate was 97.3%. PMID- 17851927 TI - Idiopathic sudden sensorineural hearing loss: results drawn from the Swedish national database. AB - CONCLUSION: The first results from 300 patients in a Swedish national database for sudden sensorineural hearing loss (SSNHL) demonstrate that corticosteroids or 'no treatment at all' are the treatment options in use today. No significant difference in outcome was seen between treated and non-treated patients. Since spontaneous recovery might be the cause, a placebo-controlled randomized study is required before a positive effect of corticosteroids can be asserted. OBJECTIVES: To investigate the treatment policy for SSNHL in Sweden, the effect on outcome, and which variables are of value in predicting the outcome. PATIENTS AND METHODS: A national database was developed in Sweden which gathers data from patients with SSNHL. A form is used for data collection covering background, current disease, examinations, and treatment. Audiograms at the onset of SSNHL and after 3 months are analyzed. RESULTS: Of 300 patients, 208 were considered to have idiopathic SSNHL; 50% were treated with corticosteroids, 44% did not receive any treatment. The treated patients had the same outcome as the non-treated patients. The time interval from onset of SSNHL to start of treatment was of importance for the outcome irrespective of type of audiogram or results from laboratory tests. Higher age and heredity for hearing loss gave a significantly lower chance of improvement. PMID- 17851929 TI - Clinical characteristics and genotype-phenotype correlation of hearing loss patients with SLC26A4 mutations. AB - CONCLUSIONS: The present study confirmed the clinical characteristics of patients with SLC26A4 mutations: congenital, fluctuating, and progressive hearing loss usually associated with vertigo and/or goiter during long-term follow-up. This clarification should help to facilitate appropriate genetic counseling and proper medical management for patients with these mutations, but there was no particular genotype-phenotype correlation among them, suggesting that other factors may contribute to such variability. OBJECTIVES: Due to the wide range of phenotypes caused by SLC26A4 mutations, there is controversy with regard to genotype phenotype correlation. The present study was performed: (1) to determine phenotypic range in patients with biallelic SLC26A4 mutations, and (2) to evaluate whether possible genotype-phenotype correlation exists. SUBJECTS AND METHODS: Phenotypes in 39 hearing loss patients with SLC26A4 mutations were summarized and genotype-phenotype correlation was analyzed. RESULTS: Hearing level varied in the individuals from mild to profound severity. Most of the patients had fluctuating and progressive hearing loss that may have been of prelingual onset. Twenty-four (70.6%) patients had episodes of vertigo, and 10 (27.8%) patients had goiter, which had appeared at age 12 or older. In contrast to such phenotypic variabilities, no apparent correlation was found between these phenotypes and their genotypes. PMID- 17851930 TI - Prevalence of human immunodeficiency virus seropositivity in head and neck malignancies in sub-Saharan Africa. AB - CONCLUSION: Salivary gland diseases should be handled with a high index of suspicion. Although an inference could be drawn it is not clear from this study if primary head and neck cancers (HNCs) have a significant association with HIV/AIDS. OBJECTIVE: HIV/AIDS manifestations and malignancies do occur in the head and neck region. The head and neck surgeon is thus involved in the early identification and management of this group of patients. This study evaluated the prevalence of HIV seropositivity in head and neck malignancies (HNMs) in our centre. MATERIALS AND METHODS: This was a 10 year (January 1996-June 2006) study of all consecutive cases of histologically confirmed HNMs seen in the ENT department of our centre. Participants had HIV screening by ELISA; those with reactive results had a further confirmatory test (mainly Western blot). Pre-test counselling preceded informed consent of each participant. Seropositive participants had post test counselling. All had surgical biopsy for histology. RESULTS: A total of 521 HNCs (6.6%) were seen in 7941 otolaryngologic consultations within the study period. Males constituted 67.4% and females 32.6% (M:F ratio 2.1:1). Their mean age was 22.1+/-13.7 years (age range 8-85 years). HNCs were most common in the sixth decade. Ten participants (six males and four females) of the study population were HIV seropositive - a prevalence of 1.9% with 70% being in the 17-45 years age group. Laryngeal cancer (n=163, 31.3%) was the most common HNC. Four (36.4%) of the 11 cases of malignant salivary gland cancers (all parotid) were HIV seropositive. More cases of HIV seropositivity were observed during the HNC peak period of 2004-2006. PMID- 17851931 TI - Association of body position with sleep architecture and respiratory disturbances in children with obstructive sleep apnea. AB - CONCLUSIONS: Sleep position in children with obstructive sleep apnea (OSA) did not affect the sleep architecture. Supine position had a significant influence on respiratory parameters and gas exchange. Lateral position did not affect respiratory parameters in children aged 3-5 years and little affected gas exchange except right lateral decubitus (RLD) position in children aged 11-13 years. Children with OSA breathe best when in the left lateral decubitus (LLD) position. OBJECTIVE: To analyze the relationship between OSA and body position during sleep in children. SUBJECTS AND METHODS: A total of 45 consecutive children (age class A: 3-5 years, n = 15; B: 6-10 years, n = 14; C: 11-13 years, n = 16) with OSA were studied. The following variables were evaluated: apnea hypopnea index (AHI) in supine, LLD, and RLD positions, sleep architecture, respiratory parameters, and oxygen saturation. RESULTS: There were no no significant differences in AHI between LLD AHI, RLD AHI, and supine position in age class A, LLD AHI was significantly lower than supine AHI in age classes B and C. There was no correlation between position AHI and sleep architecture. There was no correlation between lateral position AHI and the parameters of respiratory disturbance in age class A. The parameters of respiratory disturbance were related to LLD and RLD position in age class B; supine and RLD position in age class C were similar. Position AHI was related to some of the parameters of gas exchange except for RLD AHI in age classes A and B. PMID- 17851932 TI - Frequency discrimination with sequential or simultaneous stimulation in MED-EL cochlear implants. AB - CONCLUSION: Amplitude weighting using the bell-shaped filter design within the OPUS speech processors allows the creation of pitches intermediate to those of two adjacent electrodes. This mechanism can be used for both sequential and simultaneous stimulation. OBJECTIVES: This paper describes frequency discrimination experiments which are based on amplitude weighting of two adjacent electrodes. The effects of sequential versus simultaneous stimulation of the electrode pair were investigated. MATERIALS AND METHODS: The experiment was performed using a laboratory system emulating the signal processing using bell shaped filters in the MED-EL speech processors. The system transformed input files (wav-files) into the stimulation data stream which was transmitted to the implant via the OPUS processor coil. Pitch discrimination was assessed for up to three electrode pairs in each subject, using an adaptive test method. Results for sequential stimulation were collected in eight subjects, a comparison between sequential and simultaneous stimulation was made in five subjects. RESULTS: Results show an average frequency discrimination of 8.8% for sequential stimulation and 11.2% for simultaneous stimulation, of the nominal test frequency. Frequency discrimination ability varied across subjects and test electrode pairs. The difference in performance between sequential and simultaneous stimulation was not statistically significant. PMID- 17851933 TI - Activation patterns of the primary auditory cortex in normal-hearing subjects: a functional magnetic resonance imaging study. AB - CONCLUSIONS: These results demonstrate that functional magnetic resonance imaging (fMRI) is an optimal tool to investigate the auditory cortex. The study suggests that there is a medio-lateral gradient of responsiveness to high frequencies medially and low frequencies laterally. The contralateral auditory cortex is more responsive than the ipsilateral cortex to tones presented monaurally. OBJECTIVES: To demonstrate the activation of the primary auditory cortex in normal-hearing subjects using fMRI and to examine the response and topographic location of activation in the human auditory brain to stimulation with two different frequencies in a large group of volunteers. SUBJECTS AND METHODS: Scanning was performed on a 1.5 Tesla MR with head gradient coils and a birdcage radiofrequency coil. Multiplanar echo-planar images were acquired in 32 subjects aged between 18 and 49 years. Two groups were defined, according to age (group A, 18 to <35 years old; group B, 35 to <50 years old). We studied normal-hearing subjects scanned while listening to auditory stimuli: narrative text in one volunteer and non-speech noise (pure tones 750 Hz and pure tones 2 KHz) in all subjects. RESULTS: For both tone frequencies, auditory activation was observed bilaterally across the supratemporal plane in 29 of the 32 subjects (90.62%) with a probability level of p<0.001. In Heschl's gyrus (HG) contralateral to the stimulated ear, the extent of activation was generally greater than in homolateral HG. There were no statistical differences in HG activation according to age or sex. The 750 Hz tone activated more voxels in the medial area of the transverse temporal gyrus (TTG) whereas the 2000 Hz tone activated more voxels in the lateral TTG. PMID- 17851934 TI - Topical steroid therapy using the Silverstein Microwick in sudden sensorineural hearing loss after failure of conventional treatment. AB - CONCLUSIONS: Local administration of steroids to the inner ear through the round window route improves hearing in patients after failure of conventional therapy. OBJECTIVES: To determine if delivery of methylprednisolone to the round window can improve hearing after failure of conventional treatment for sudden sensorineural hearing loss (SSHL) administered for 10 days after the onset of the hearing loss. PATIENTS AND METHODS: A Silverstein microwick was placed in the round window niche under local anesthesia and endoscopic control, allowing self administration of methylprednisolone twice a day for 3 weeks. Treated patients were compared to a control group composed of similar patients, treated with the same systemic regimen but who did not receive local therapy. RESULTS: Of the 12 patients enrolled in this nonrandomized prospective study, 8 patients showed an improvement of the pure tone average (PTA) and 4 remain stable. Of those who responded to perfusion, eight patients demonstrated a significant mean 24.5 +/- 12 dB improvement in PTA, and seven patients had a mean 17.5 +/- 18% improvement in discrimination, with five patients reaching 100% speech discrimination score (SDS). Patients in the control group did not show any improvement of the PTA. PMID- 17851935 TI - Bacteriology of chronic suppurative otitis media--a multicenter study. AB - CONCLUSIONS: Bacterial predominance and antibiotic sensitivity have changed over time, making continuous and periodic surveillance necessary in guiding appropriate antibacterial therapy. OBJECTIVES: With the development and widespread use of antibiotics, the types of pathogenic microorganisms and their resistance to antibiotics have changed. Knowledge of the species and resistance rates of current pathogens is important for determining the appropriate antibiotics for patients with chronic suppurative otitis media. We investigated the current bacteriology of chronic suppurative otitis media. SUBJECTS AND METHODS: This was a retrospective study of 1102 patients with chronic suppurative otitis media seen at six hospitals in Korea from January 2001 to December 2005. RESULTS: The most commonly identified pathogenic bacterial species was Pseudomonas, with the next most prevalent being methicillin-resistant Staphylococcus aureus (MRSA). PMID- 17851936 TI - Mucin gene expression in hypertrophic adenoids. AB - CONCLUSION: Membrane-bound mucin MUC4 represents the predominant mucin expressed in the adenoid epithelium followed by MUC5AC (gel-forming mucin). This may suggest that membrane-bound mucins could be involved in pathogen binding and immunological stimulation. OBJECTIVES: The aim of this study was to investigate mucin expression in hypertrophic adenoids. MATERIALS AND METHODS: Adenoidal samples were obtained from 12 children. The expression of eight mucin genes, MUC1 4, MUC5AC, 5B, 6 and 7 was studied by in situ hybridization utilizing digoxigenin labelled oligonucleotide probes. RESULTS: The dominant mucin genes were MUC4, 3 and 5AC, while MUC1, 2, 5B and 7 were sparsely expressed and MUC6 was not expressed. Expression patterns were very different from those in the upper airways. Most samples expressed two membrane-bound mucins (MUC4 and 3) and one secretory mucin (MUC5AC). PMID- 17851937 TI - Gustatory function after microlaryngoscopy. AB - CONCLUSION: Quantitative gustatory alterations are rare after microlaryngoscopy (MLS), whereas transient qualitative taste distortions occur more often. Patients undergoing MLS should know that mild but transient qualitative taste disorders may occur. OBJECTIVE: Suspension MLS requires neck extension and tongue compression. Little is known about taste disorders following MLS. To investigate qualitative and quantitative gustatory function after MLS we tested and questioned patients before and several weeks after the MLS. SUBJECTS AND METHODS: This was a prospective controlled study carried out in a tertiary care centre. Forty-three patients participated, 33 of whom underwent MLS and 10 septoplasty. Tongue compression time was recorded during MLS. Patients received taste evaluation before and at 1 and 14 days after the intervention. Patients were asked to indicate subjectively changed taste perceptions. RESULTS: Psychophysical (quantitative) taste results showed no significant differences before and at 1 and 14 days after the intervention (p = 0.60). Tongue compression time (MLS group) had no influence on measured post-MLS taste scores. In the MLS group four patients reported distorted taste perception the day after the MLS, whereas no patient in the septoplasty group did so. In all, four patients distorted taste perception, had disappeared after 14 days. PMID- 17851938 TI - Human auditory nerve compound action potentials and long latency responses. AB - CONCLUSION: The compound action potential (CAP) is followed by a long latency response (LLR), attributable to the post-auricular musculature. The LLR to one pulse may overlap with the CAP to a subsequent one, contributing to the clinically observed reduction in CAP at high pulse rates. OBJECTIVES: To measure refractory and other influences on CAPs in humans and guinea pigs. MATERIALS AND METHODS: CAPs were obtained from humans using trans-tympanic and extra-tympanic electrocochleography and from anaesthetized guinea pigs. Stimuli were single pulses presented at a slow rate, pairs of pulses, and 100 ms pulse trains where the inter-pulse interval alternated between 4 and 6 ms. RESULTS: For single pulses, the CAP shape was similar across species. For pairs of pulses, the CAP to the second pulse was smaller than that to the first, and decreased with increasing inter-pulse interval in a way that was similar across species. For pulse trains, CAPs were observed in response to each pulse in the train for the guinea pigs, but not for humans. For both filtered and unfiltered single pulses, there was a large LLR in humans, but not in guinea pigs, with peaks at latencies of 10-12 and 20-25 ms. Posture affected the LLR in a way consistent with the post auricular response. PMID- 17851939 TI - Evaluation of the systemic use of riluzole in post-traumatic facial nerve regeneration: experimental study in rabbits. AB - CONCLUSIONS: Riluzole promoted increase and/or preservation of axon density in the animals treated with this drug as compared to the control group; it did not increase the mean diameter of facial nerve fibres as compared to the non-treated group; and it did not provide a better functional motor recovery than in the control group. OBJECTIVE: Traumatic peripheral facial paralysis is a frequent affection. In incomplete nerve injuries, systemic drugs acting on regeneration may decrease the patient's period of morbidity. This study aimed to determine the effect of the drug riluzole on regeneration of the facial nerve of rabbits submitted to post-traumatic facial paralysis. MATERIALS AND METHODS: Eighteen rabbits were submitted to compression of the facial nerve and divided into control (A) and treated (B) groups. The animals were sacrificed 4 weeks after the injury and their nerves were studied regarding density of myelinated axons and measure of external axon diameters. RESULTS: Partial functional recovery was observed within 2 weeks and complete recovery 5 weeks after injury. Mean neural density was 12,679.7 axons/mm2 (SD+/-237.5) in group A, and 19,073.8 axons/mm2 (SD+/-3549.9) in group B. Group A presented less than two-thirds the density of group B. There was no statistical difference in axon diameters between the studied groups. PMID- 17851940 TI - Long-term results of surgical treatment for recurrent respiratory papillomatosis. AB - CONCLUSIONS: The presented results add further support to the observation that laser microsurgery is the preferential surgical treatment for recurrent respiratory papillomatosis (RRP). A meticulous follow-up for early recognition of local recurrence and malignant transformation is recommended. OBJECTIVES: Endoscopic microsurgery continues to be the treatment of choice for RRP. The aim of this study was to evaluate the outcome of patients treated surgically. We focused on demographic data, recurrence rates, and treatment-related complications. PATIENTS AND METHODS: The charts of 194 patients treated at our institution between 1963 and 1993 were analyzed retrospectively. RESULTS: In all, 64 patients (33%) underwent a total of 137 operations using the CO2 laser; 130 patients (67%) underwent a total of 565 microlaryngeal operations by surgery with cold instruments. Five percent of the patients treated with conventional microlaryngeal surgery and none of the patients treated with laser surgery required tracheostomy (p<0.05). Postoperative glottic webs and scar formations were found in 6% of all patients after laser surgery and 20% after conventional surgery (p<0.05). The different methods of treatment did not affect the rate of recurrence (p=0.61) Malignant transformation or secondary airway carcinoma were observed in 4% of all patients. PMID- 17851941 TI - Treatment of hypertrophic palatine tonsils using bipolar radiofrequency-induced thermotherapy (RFITT.). AB - CONCLUSION: Radiofrequency volume reduction of palatine tonsils is a gentle and safe treatment method in selected patients, which should carefully be considered as an alternative to tonsillectomy or tonsillotomy. OBJECTIVES: The aim of this study was the evaluation of bipolar radiofrequency-induced thermotherapy (RFITT) compared to standard blunt dissection tonsillectomy (TE) for the volume reduction of palatine tonsils in chronic tonsillar hypertrophy. PATIENTS AND METHODS: A total of 137 patients (98 children) were treated in two groups in a prospective controlled, randomized clinical trial. The TE group underwent standard tonsillectomy using blunt dissection. The RFITT group underwent interstitial RF ablation. Perioperative blood loss and duration of surgery were monitored. Tonsil volume reduction in the RFITT group was measured by sonography. Postoperative pain, as well as difficulty in swallowing and speaking, were evaluated using visual analog scales. RESULTS: In the RFITT group, we found an average tonsil volume reduction of 40%, at about 3 weeks after treatment. Postoperative pain, swallowing and speaking difficulties, and perioperative blood loss were significantly lower, and the duration of surgery was significantly shorter (all p<0.05) in the RFITT group. Preservation of the treatment results was monitored until 6 months after treatment, with no after effects during this time period. PMID- 17851942 TI - Otologic T-tube in endonasal dacryocystorhinostomy: a new approach. AB - CONCLUSION: Otologic T-tubes had a success rate of 73% if implanted during endoscopic dacryocystorhinostomy (DCR). We suggest that they can be used successfully in endoscopic DCR, and are promising as an alternative to silicone stent intubations. OBJECTIVE: To evaluate the efficacy of endoscopic DCR using otologic T-tube. MATERIALS AND METHODS: Twenty patients (22 eyes) with nasolacrimal duct obstruction underwent endoscopic DCR. After creating an aperture in the medial wall of the lacrimal sac, the otologic T-tube (1.15 mm diameter, Invotec, Jacksonville, FL, USA) was inserted into the sac transnasally. The T-tube was left in the lacrimal sac for between 3 and 6 months. The patients were followed up for between 6 and 24 months (mean 12.4 months). The improvement in patients' epiphora complaint was grouped as very good, good, or no change. RESULTS: Eleven eyes (50%) proved to be 'very good', whereas five eyes (23%) were good, and six eyes (27%) had no change. Of six eyes that were reported to have no change after the operation, three experienced spontaneous tube loss in the early period, one eye was a recurrent case, and the other two were primary cases. PMID- 17851943 TI - Immunohistochemical evidence of BMP-2, -4 and -7 activity in otospongiosis. AB - CONCLUSION: This study is the first to show that bone morphogenetic proteins (BMP)-2, -4 and -7 play a role in active phase otosclerotic bone remodelling (otospongiosis). OBJECTIVES: The role of BMPs in various tissue growth and repair mechanisms is an ongoing topic in the literature. BMP-2, -4 and -7 are known to be of major importance in bone formation and repair. Their role in otosclerotic bone transformation has not been analysed previously. The main goal of this study was to perform an immunohistological analysis of BMP-2, -4 and -7 in otoclerosis. MATERIALS AND METHODS: Parts of the stapedial footplates, collected during partial stapedectomies in 30 patients with clinical otosclerosis, were analysed for histological otosclerotic lesions after staining haematoxylin and eosin. Immunohistochemical analysis was performed using polyclonal IgG antibodies for BMP-2, -4 and -7, as well as biotinylated secondary antibodies, avidin-biotin peroxidase complex reaction and alkaline phosphatase staining. RESULTS: In all, 14 specimens contained otosclerosis; 3 of these were otospongiotic, 8 fibrotic, 2 sclerotic and 1 had both sclerotic and fibrotic lesions. Thus in total 14/30 specimens (47%) showed histological otosclerosis. Only the multiple osteoblasts and osteoclasts in those specimens exhibiting an otospongiotic phase showed distinct immunochemical staining for BMP-2, -4 and -7. PMID- 17851944 TI - Laminin expression in juvenile angiofibroma indicates vessel's early developmental stage. AB - CONCLUSION: This study confirms the wide range of vascular architecture in juvenile angiofibromas. Proof of laminin alpha2 expression in tumour vessels is suggested to indicate presence of vessels of early developmental stage in juvenile angiofibromas, supporting the concept that plexus remnants of the first branchial arch artery contribute to the vascular tumour component. OBJECTIVES: Laminins, one of the major components of vascular wall basement membranes, have been implicated in tumour growth and have been shown to have developmentally regulated expression patterns. The goal of this study was to analyse the expression of laminins in juvenile angiofibromas. MATERIALS AND METHODS: A detailed analysis of the laminin isoform expression was performed by immunofluorescence staining for laminin chains alpha1, alpha2, alpha3, alpha4, alpha5, beta1, beta2, beta3, gamma1, gamma2, and gamma3 on cryosections of 10 juvenile angiofibromas and inferior nasal turbinate tissue for control. RESULTS: Vascular staining of the different laminin chains revealed areas of differential vessel density in juvenile angiofibromas and irregularities in vessel size, configuration and architecture. Similar to vessels in nasal turbinates, laminins alpha4, alpha5, beta1, beta2 and gamma1 were found to be expressed in juvenile angiofibroma vessels. In contrast to vessels of nasal turbinates, staining for alpha2 and alpha3 chains was only detected in vessels of juvenile angiofibromas. PMID- 17851945 TI - Primary tumor volume calculation as a predictive factor of prognosis in nasopharyngeal carcinoma. AB - CONCLUSIONS: Primary tumor volume (PTV) has a close relationship with survival rates of patients with nasopharyngeal carcinoma (NPC) who were treated with concurrent chemoradiotherapy (CCRT) or radiotherapy. Besides the current AJCC staging system, measurement of PTV may be needed to predict prognosis of NPC and adjust treatment strategy. OBJECTIVES: We conducted a retrospective study to elucidate the effect of PTV on treatment outcomes in patients with NPC who were treated with CCRT or radiotherapy. PATIENTS AND METHODS: A total of 66 patients with newly diagnosed NPC were enrolled in this study. Computed tomography (CT) derived or magnetic resonance imaging (MRI)-derived PTV was calculated. The correlation between AJCC disease stage, PTV, and disease-specific survival was analyzed. Correlations between different prognostic factors were assessed using a Cox regression model. RESULTS: The median PTV for the whole series was 12.01 ml (range 1.25-166.58 ml). The median PTV was 3.45 ml in T1 disease, 7.96 ml in T2 disease, 17.95 ml in T3 disease, and 64.73 ml in T4 disease. Disease stage and T stage carried no prognostic significance (p=0.25 and p =0.30, respectively). Four categories of PTV (<12.5 ml, 12.5-25 ml, 25-50 ml and >50 ml) had prognostic significance (p=0.02). Survival analysis demonstrated a significant difference in overall survival with larger tumor volume (risk ratio 5.447; p=0.044). PMID- 17851946 TI - Deep neck infection with dental origin: analysis of 85 consecutive cases (2000 2006). AB - CONCLUSIONS: Diagnostic work-up should include contrast-enhanced computed tomography (CT) and mandible orthopantogram. When a dental origin of deep neck infection is suspected, the intravenous antibiotic regimen has to be active against gram-positive bacteria, both aerobes and anaerobes. Surgical exploration and drainage may be mandatory at presentation, or in cases not responding to medical therapy within the first 24 h. OBJECTIVES: Deep neck infections are still associated with significant morbidity and mortality rates when complications occur. Despite worldwide improvement in dental care and oral hygiene, a significant prevalence of deep neck infections caused by dental infections has been described recently (> 40%). PATIENTS AND METHODS: We analysed retrospectively 85 cases of deep neck infection with dental origin out of 206 consecutive cases of deep neck infection diagnosed in our institution between 2000 and 2006. RESULTS: The most frequent dental source was a periapical infection of the first mandibular molar, followed by second and third molar, respectively. Submandibular space infection involvement was diagnosed in 73 of 85 patients (85.9%), masticatory space infection in 28 (32.9%); in 56 patients (65.9%) the infection involved more than one space. Twenty-four patients (28.2%) were treated only with intravenous antibiotic therapy; 61 patients (71.8%) required both medical and surgical procedures. PMID- 17851947 TI - The benefits of sequential bilateral cochlear implantation for hearing-impaired children. AB - CONCLUSION: Sequential bilateral implantation offers listening advantages demonstrable on speech recognition in noise and for lateralization. Whilst the trend was for shorter inter-implant intervals and longer implant experience to positively impact binaural advantage, we observed no contraindications for binaural advantage. OBJECTIVE: To evaluate the benefits of sequential bilateral cochlear implantation over unilateral implantation in a multicentre study evaluating speech recognition in noise and lateralization of sound. SUBJECTS AND METHODS: Twenty children, implanted bilaterally in sequential procedures, had the following characteristics: they were native German-speaking, were3 years or older and had a minimum of 1 year inter-implant interval and had between 2 months and 4 years 7 months binaural listening experience. Binaural advantage was assessed including speech recognition in noise using the Regensburg modification of the Oldenburger Kinder-Reimtest (OLKI) and lateralization of broadband stimuli from three speakers. RESULTS: A significant binaural advantage of 37% was observed for speech recognition in noise. Binaural lateralization ability was statistically superior for the first and second implanted ear (p = 0.009, p = 0.001, respectively). Binaural experience was shown to correlate moderately with absolute binaural speech recognition scores, with binaural advantage for speech recognition and with binaural lateralization ability. The time interval between implants correlated in an inverse direction with binaural advantage for speech recognition. PMID- 17851948 TI - Planned neck dissection before combined chemoradiation for pyriform sinus carcinoma. AB - CONCLUSIONS: A pretreatment neck dissection in a chemoradiation regimen for pyriform sinus carcinoma provides no delay for radiation, low complication rates, optimal radiation doses and a high nodal disease control. OBJECTIVES: The aims of this study were to evaluate the clinical feasibility, therapeutic consequences and neck nodes control of a pretreatment neck dissection in a chemoradiation regimen for organ preservation strategy for pyriform sinus carcinoma. PATIENTS AND METHODS: Seventy-six patients with untreated stage III and IV squamous cell carcinoma of the pyriform sinus were included in this study. Eighty neck dissections were performed according to the N status. Dose of radiotherapy was delivered according to the pathologic finding of neck dissections. RESULTS: The mean time between neck dissection and the chemoradiation was 24 days (+/-12 days). Only two patients (2.5%) experienced wound complications. A 'boost' radiation of 14 Gy was delivered after 49 neck dissections (61%) in patients with extracapsular spread. The rate of disease control within the regional nodes was 90%. The Kaplan-Meier 1- and 2- year overall survival rates were 78% and 43%, respectively, and specific survival rates were 88% and 67%, respectively. PMID- 17851949 TI - Gram-negative pathogen Klebsiella oxytoca is associated with spontaneous chronic otitis media in Toll-like receptor 4-deficient C3H/HeJ mice. AB - CONCLUSION: This report confirms the presence of gram-negative Klebsiella bacteria in the middle ear of the C3H/HeJ mouse by culture, polymerase chain reaction (PCR), and electron microscopy. Identification of the bacterial pathogen supports the C3H/HeJ mouse as an excellent model for spontaneous chronic otitis media and its effects on the middle and inner ear. OBJECTIVES: The C3H/HeJ mouse has a single amino acid substitution in its Toll-like receptor 4, making it insensitive to endotoxin and suppressing initiation of the innate immune system. This study explored the bacteriology of the resultant middle ear infection by culture, PCR, histology, and electron microscopy. MATERIALS AND METHODS: Twelve month-old C3H/ HeJ mice were screened positive for spontaneous otitis media. Tympanocentesis and blood cultures of mice were carried out under sedation. Middle ear aspirate material and blood samples were then sent for culture and PCR. Mice were then sacrificed for bright-field and electron microscopy analysis. RESULTS: All tympanocentesis and blood specimens grew gram-negative Klebsiella oxytoca, which was confirmed by PCR. Histopathology confirmed an intense inflammatory reaction and gram-negative bacteria in the middle and inner ears. Electron microscopy of the middle ears revealed abundant rod-shaped Klebsiella bacteria, both free and being engulfed by neutrophils. PMID- 17851950 TI - The effect of unilateral multichannel cochlear implant on bilaterally perceived tinnitus. AB - CONCLUSIONS: Available multichannel cochlear implants (CIs) provide effective tinnitus suppression. More sophisticated speech strategies are more effective than analogue or slow strategies. The mechanisms by which tinnitus is suppressed by CIs are unclear; however, both acoustic masking and reorganization of the right auditory association cortex induced by the CI are possible mechanisms. CI significantly reduced the tinnitus-related Handicap as assessed by the Tinnitus handicap Inventory (THI). OBJECTIVE: The objective of the study was to evaluate the effects of a unilateral CI on bilaterally perceived tinnitus. PATIENTS AND METHODS: Forty-one profoundly deaf patients implanted with a multichannel CI reporting bilateral tinnitus were evaluated. All patients were asked to complete a questionnaire that evaluated the presence, location and intensity of tinnitus before and after cochlear implantation. RESULTS: Seven patients (17%) reported the perception of a 'new tinnitus' after surgery. With the CI off tinnitus was abolished in 23 patients (56.1%) in the implanted ear and in 22 patients (53.6%) in the contralateral ear. With the CI on tinnitus was abolished in the ipsilateral ear in 27 patients (65.8%) and in the contralateral ear in 27 patients (65.8%). Statistical analysis showed a significant reduction of the total THI score and of each subscale score (p < 0.001). PMID- 17851951 TI - Vitamin E and vitamin C in the treatment of idiopathic sudden sensorineural hearing loss. AB - CONCLUSION: The results of this study suggest that the administration of vitamin E and vitamin C to patients with idiopathic sudden sensorineural hearing loss (ISSHL) has beneficial effects by reducing the level of reactive oxygen metabolites produced by inner ear ischaemia and reperfusion injury after treatment. OBJECTIVES: The purpose of this study was to investigate the efficacy of antioxidant vitamin E and vitamin C in the treatment of ISSHL. PATIENTS AND METHODS: In a retrospective chart review, a total of 87 patients were enrolled who fulfilled the following inclusion criteria: 1) sudden onset of sensorineural hearing loss, 2) cause of hearing loss unknown, 3) hearing loss did not fluctuate, 4) arithmetic mean of hearing levels at 250, 500, 1000, 2000 and 4000 Hz exceeded 40 dB and 5) treatment was started within 14 days from the onset of hearing loss. All the patients were treated with steroids and/or alprostadil. In the study group, patients additionally received vitamin E (tocopherol nicotinate, 600 mg/day) and vitamin C (1200 mg/day) orally. RESULTS: The hearing gain after therapy was 29.4 dB and the improvement rate was 63.3% in the study group, compared with 18.5 dB and 44.0% in the control group. Significant improvement was seen in the hearing gain and recovery rate in the study group. PMID- 17851952 TI - Odiosoft-Rhino versus rhinomanometry in healthy subjects. AB - CONCLUSION: Odiosoft-Rhino (OR) is a non-invasive test that is completed in an extremely short period of time. It is easy to perform and little patient cooperation is needed. OR is safe and could be used in the rhinological setting if further improved. OBJECTIVE: To evaluate nasal obstruction objectively with a new technique, OR, and to compare the results with a widely accepted method, rhinomanometry, in normal subjects. SUBJECTS AND METHODS: OR and anterior RMM were performed in 79 subjects without any rhinologic symptoms and signs. Visual analogue scales (VAS) of nasal obstruction, nasal airway resistance and nasal expiratory and inspiratory sounds were analysed. RESULTS: VAS of nasal obstruction was found to be correlated with OR findings of expiration at 2000 4000 Hz frequency interval on both sides (r = 0.564, p < 0.01 for the left side, r = 0.533, p < 0.01 for the right side). Correlations were found (p < 0.05) between left 2000-4000 Hz in expiration OR and left expiration RMM, left 4000 6000 Hz in expiration OR and left expiration RMM, right 2000-4000 Hz in expiration OR and right expiration RMM, and right 4000-6000 Hz in expiration OR and right expiration RMM. No correlation was seen between VAS, anterior RMM and OR at inspiration in any interval. PMID- 17851953 TI - Epidemiological aspects of vertigo in the general population of the Autonomic Region of Valencia, Spain. AB - CONCLUSION: Vertigo, defined as an illusion of unequivocal rotatory motion, is a common symptom in the general population that frequently requires individuals to seek medical attention in a primary care centre. OBJECTIVES: To evaluate the annual incidence of patients who suffer vertigo, and to examine some of the variables associated, in a sample of the general population of the Autonomic Region of Valencia, Spain. SUBJECTS AND METHODS: The study was designed as an observational, incidence study. The study area included six primary care centres with a total population of 10760 inhabitants. The parameters studied were age, sex, working status, de novo presentation or recurrent vertigo crisis. RESULTS: A total of 191 patients (17.8 patients per 1000 inhabitants) sought medical attention because of vertigo over the year of the study. Of these, 82 patients (7.6 per 1000 inhabitants) experienced vertigo for the first time, a de novo crisis. Women were more often affected and the crises occurred more frequently in individuals between 50 and 60 years of age. The work status had influence on the results obtained. PMID- 17851954 TI - Dynamics of canal response to head-shaking test in benign paroxysmal positional vertigo. AB - CONCLUSIONS: Time constant and maximum slow phase velocity (SPV) of head-shaking nystagmus (HSN) demonstrated a differential canal response to head shaking in 24% of patients with posterior canal benign paroxysmal positional vertigo (BPPV). We suggest that vestibular lithiasis has a limited contribution to the mechanism that generates HSN. OBJECTIVE: To determine the canal response to head shaking in BPPV. PATIENTS AND METHODS: This was a case-control study including 104 individuals with BPPV. The diagnosis was based on the presence of vertigo and nystagmus during the positional test. Subjects were examined by the horizontal and vertical head-shaking test. Eye movements were recorded on a video camera to analyze the nystagmus. The head was shaken passively in the horizontal and sagittal planes, respectively, for horizontal and vertical HSN at a frequency of 2 Hz. HSN was considered when six consecutive beats of nystagmus with an SPV of at least 2 degrees/s were detected. Main outcome measures were the presence of horizontal and vertical HSN, maximum SPV of HSN, time constant of HSN, and canal paresis. RESULTS: Maximum SPV of vertical HSN was higher in BPPV patients with posterior canal BPPV (n = 10) than in controls (p = 0.04). Moreover, the time constant of vertical HSN was significantly lower for posterior canal BPPV when compared with controls (p < 0.02). PMID- 17851955 TI - Treatment results and prognostic factors in locally advanced hypopharyngeal cancer. AB - CONCLUSIONS: We suggest that concurrent chemoradiation (CCRT) is an effective definitive treatment for patients with advanced hypopharyngeal carcinoma who are unfit for or refuse surgery. A high dose of radiation (> 70 Gy) should be given to achieve acceptable local control rates and survival. OBJECTIVES: The purpose of this retrospective study was to compare the treatment results of locally advanced hypopharyngeal carcinoma with two different protocols. PATIENTS AND METHODS: From December 1995 to December 2004, 74 patients with locally advanced hypopharyngeal cancer were treated with CCRT or surgery plus postoperative radiotherapy (SRT). Their treatment results were reviewed by retrospective analysis. The study points included outcome, toxicity, and prognostic factors. RESULTS: There was no significant difference in T and N status between the two treatment groups, nor were there significant differences in overall or disease free survival or the incidence of distant metastasis (p >0.05). In the CCRT group and SRT group, the estimated 3-year overall survival was 39% and 44%, respectively. The SRT group had better local control than the CCRT group (p <0.05). Relatively, 27% patients retained their larynx function for more than 2 years in the CCRT group. Radiation doses >70 Gy yielded significantly better survival and local control than doses <70 Gy (p <0.05). PMID- 17851956 TI - Laryngeal fractures: clinical findings and considerations on suboptimal outcome. AB - CONCLUSION: We recommend early surgical exploration and fixation for patients with dislocated or comminuted laryngeal fractures to avoid long-term voice complications. One-third of 33 fracture patients rated their voice after the fracture had healed as fair but altered. OBJECTIVES: To examine the indications for and the outcome of surgical management in patients with laryngeal fractures. PATIENTS AND METHODS: The study was carried out in a tertiary care referral university hospital and was a retrospective study of case series. Thirty-three consecutive patients, aged 14-84 years, presented with various types of laryngeal fractures. Patients were staged according to the type of the fracture and surgical correction was performed when indicated. Voice outcome was documented and patients with subjectively suboptimal result were further evaluated by phoniatric specialist. RESULTS: In all, 32 of 33 laryngeal fracture patients had blunt trauma and the main causative factors were sport injuries (39%) and physical assault (33%). All of the 33 laryngeal fracture patients had a good airway outcome. The subjective voice outcome was good for 20 (61%) and fair for 13 (39%) patients. The mean follow-up time was 39.5 months (range 2-114 months). In phoniatric evaluation most (six of eight) patients with fair voice outcome could not produce high pitched voices because of inability to stretch the vocal folds. PMID- 17851957 TI - Prostaglandin E1 in combination with hyperbaric oxygen therapy for idiopathic sudden sensorineural hearing loss. AB - CONCLUSIONS: Prostaglandin E1 (PGE1) is less effective than stellate ganglion block (SGB) in the treatment of idiopathic sudden sensorineural hearing loss (ISSNHL) patients with severe hearing losses when used together with hyperbaric oxygen (HBO) therapy. In contrast with the systemic action of intravenous PGE1, SGB's localized vasodilating action may explain its advantage over intravenous PGE1. OBJECTIVES: To investigate the effect of PGE1 plus HBO therapy on ISSNHL in comparison with that of SGB plus HBO therapy. PATIENTS AND METHODS: We retrospectively analyzed 205 consecutive patients with ISSNHL (hearing levels > or = 40 dB; time from the onset of hearing loss to the start of treatment < or = 30 days). Ninety-five patients underwent intravenous PGE1 plus HBO therapy (PG group) and 110 underwent SGB plus HBO therapy (SGB group). Hearing recovery was evaluated by grade assessment and by hearing improvement compared to that in the unaffected contralateral ear. RESULTS: The overall hearing outcome was not statistically different between the two groups. For patients with initial hearing levels <80 dB, the groups had roughly equivalent hearing outcomes, whereas in patients with initial hearing levels > or = 80 dB, the hearing improvement rate was significantly higher in the SGB group than in the PG group (53.0 +/- 5.0% vs 35.3 +/- 6.8%; p <0.05). PMID- 17851958 TI - Partial middle turbinectomy during endoscopic sinus surgery for extended sinonasal polyposis: short- and mid-term outcomes. AB - CONCLUSIONS: The 23 patients with extensive sinonasal polyposis who had undergone partial resection of the middle turbinate during functional endoscopic sinus surgery (FESS) showed no differences in nasal airway resistance and in postoperative complication rate (1-year follow-up period) in comparison with the 25 patients who had FESS with middle turbinate preservation. OBJECTIVE: The aim of the study was to investigate the outcomes of partial middle turbinectomy during FESS in patients with sinonasal polyposis. PATIENTS AND METHODS: A retrospective analysis of 48 consecutive patients who had undergone surgery for extended sinonasal polyposis was performed. Twenty-three patients underwent FESS with middle turbinate head resection; 25 patients underwent FESS with preservation of middle turbinate. We endoscopically scored polyposis extension and evaluated nasal airflow resistance (NAR) preoperatively and postoperatively. RESULTS: We found an improvement of endoscopic score (high to low grade of polyposis extension) and a statistically significant reduction of NAR after both surgical techniques. There was no statistically significant difference in the mean NAR values before and after the two techniques. PMID- 17851959 TI - Activities of matrix metalloproteinases and tissue inhibitor of metalloproteinase 2 in idiopathic hemotympanum and otitis media with effusion. AB - CONCLUSION: The expression profile of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-2 (TIMP-2) was specific to the type of middle ear effusion. Further studies are necessary for elucidating its correlation with the sequelae of otitis media with effusion (OME) and idiopathic hemotympanum. OBJECTIVES: We aimed to investigate the relative activities of gelatinases (MMP-2 and -9), stromelysin-1 (MMP-3), and matrilysin-1 (MMP-7), as well as measuring TIMP-2 levels in the serous and mucous effusions of OME and hemorrhagic effusion of the idiopathic hemotympanum. MATERIALS AND METHODS: Middle ear effusions were collected from patients with OME and idiopathic hemotympanum, and were classified as mucoid, serous, or hemorrhagic. MMP activity in the effusion samples was examined by gelatin and casein zymography. Levels of TIMP-2 were measured by ELISA. Human temporal bone sections, with and without otitis media (OM), were examined histologically. RESULTS: One case showed tympanic membrane thinning in the OM group, but none in the control group. While MMP-2 was present in all effusions, the active form of MMP-2 was found only in mucous effusions. MMP-3 and MMP-7 activity was detected only in the mucous effusions. MMP-9 exhibited activity in all effusions, with the highest levels in mucous effusions. TIMP-2 levels were markedly elevated in serous effusions. PMID- 17851960 TI - A new animal model for Meniere's disease. AB - CONCLUSION: A new murine model for the study of Meniere's disease has been developed by treatment with both lipopolysaccharide (LPS) and aldosterone. Induction of vestibular dysfunction in the hydropic animal model may entail additional stress such as reduced inner ear blood flow, and sudden acute changes in endolymph volume and/or pressure. OBJECTIVE: The purpose of this study was to develop a more suitable animal model, showing closer resemblance to the pathophysiological process in Meniere's disease. MATERIALS AND METHODS: Adult CBA/J mice were treated by intratympanic injection of LPS, intraperitoneal injection of aldosterone, or injection of both LPS and aldosterone. Morphological analyses were performed in the cochlea and endolymphatic sac. RESULTS: All experimental animals showed mild to moderate endolymphatic hydrops. Those treated with both LPS and aldosterone showed reversible vestibular dysfunction after the intratympanic injection of epinephrine. PMID- 17851961 TI - Speech-in-noise intelligibility does not correlate with efferent olivocochlear reflex in humans with normal hearing. AB - CONCLUSION: According to the presented data, speech-in-noise intelligibility (SI) does not correlate with olivocochlear efferent activity - as measured by contralateral suppression (CS) of distortion product otoacoustic emissions (DPOAE) in humans with normal auditory threshold. OBJECTIVES: Literature data indicate a possible role of the medial olivocochlear efferents in speech intelligibility, especially in background noise. The objective of this study was to investigate this relationship. MATERIALS AND METHODS: SI was evaluated in three independent sessions by determining the ratio speech level/noise level, at which 50% of the words are understood (i.e. speech reception threshold, SRT). Efferent activity was inferred measuring CS of DPOAE, using two different paradigms with extensive variation of stimulus parameters and duplicate measurements. RESULTS: For optimum measurement of CS, the study was restricted to subjects (n =49) with valid DPOAE down to primary tone levels L1=47/L2 =20 dB SPL. Average SRT was -6.66 dB (-4.50 to -7.65 dB, SD 0.63 dB). CS increased with decreasing primary tone levels, with mean absolute CS values in the range of 0.6 6 dB SPL. Test-retest repeatability was good. Statistical evaluation revealed no significant relationship between SI and CS of DPOAE. PMID- 17851963 TI - Hearing progress and fluctuations in bimodal-binaural hearing users (unilateral cochlear implants and contralateral hearing aid). AB - CONCLUSIONS: Mean scores achieved using a cochlear implant (CI) plus a hearing aid (HA) were consistently higher (statistically non-significant) than those for CI alone. The addition of a contralateral HA partially compensated for the negative hearing fluctuations as well as for the slow initial progress with the CI. OBJECTIVES: To examine hearing progress over the first 3 years after unilateral cochlear implantation in users who had residual hearing in the non implanted ear at the time of surgery and continued to use a HA in that ear thereafter. PATIENTS AND METHODS: Thirteen patients were followed up for 36 months after continuous concomitant use of a CI and a contralateral HA. To evaluate hearing progress, sentence identification in background noise (presentation level, 55 dB; S/N ratio, +10 dB) was tested for CI alone and for CI with contralateral HA (CI+HA). Subjects were tested after 6, 12, 18, 24, and 36 months of concomitant use of both devices. Mixed regression model was used to evaluate the group's progression of scores and the added value of a contralateral HA over time. RESULTS: When last tested (36 months after CI) the mean group score for CI alone was 72.6% +/- 19.3%, and 12/13 patients scored at least 65% with either CI alone or CI+HA. Mean scores achieved using CI+HA were consistently higher than those for CI alone. Percentage improvement in CI+HA relative to CI alone was highest (19.2%) after 18 months of concomitant usage and then diminished gradually to 7.7% at 36 months. Most patients showed some negative fluctuations in performance with CI alone at some point during the 36 months of post-CI follow-up. PMID- 17851962 TI - Age-related differences in parameters of vestibular evoked myogenic potentials. AB - CONCLUSIONS: The statistically significant correlations between vestibular evoked myogenic potential (VEMP) parameters and age may be due to hair cell loss of the otolith organ and/or to degenerative changes of the vestibular neural pathway. These findings indicate that age should be taken into account when interpreting VEMP results. It is also important to determine a standard method for performing VEMP and a universal index for comparison among laboratories. OBJECTIVES: VEMP, which measures the surface electric potential from the cervical muscle evoked by sufficiently loud sounds, is a useful tool to evaluate vestibule-colic reflex function. We have assayed the effect of age on VEMP results. SUBJECTS AND METHODS: After excluding subjects with a previous history of dizziness, middle ear pathology, or other inner ear symptoms, a total of 97 healthy volunteers (194 ears) were included. All VEMP parameters were analyzed to find differences related to side and gender, as well as the relationship between age and each VEMP parameter. RESULTS: Age was correlated with all VEMP parameters. Latency of p13, n23 showed a negative correlation and amplitude of p13-n23 showed a positive correlation with age. Differences between the right and left sides were not significant. PMID- 17851964 TI - Quantitative analysis of mRNA in human temporal bones. AB - CONCLUSION: Well-preserved mRNA could be extracted from frozen human inner ears. Therefore, this study demonstrates that analysis of mRNA could be performed to study the molecular mechanisms of inner ear disorders using human specimens. OBJECTIVES: Analysis of RNA as well DNA is requisite to study the molecular mechanisms of inner ear disorders. Methods of isolating RNA from experimental animals have been established, while isolation of RNA from human inner ears is much more challenging. In the present study, we demonstrate a method by which messenger RNA (mRNA) was extracted from human inner ears and quantitatively analyzed. MATERIALS AND METHODS: COCH mRNA as well as GAPDH mRNA was extracted from membranous labyrinths dissected from three formalin-fixed and three frozen human temporal bones, removed at autopsy. The length of COCH mRNA and quantity of GAPDH mRNA was compared between the two groups by quantitative RT-PCR. RESULTS: COCH mRNA could be amplified as much as 976 bp in all three frozen specimens. By contrast, it was amplified to 249 bp in two of the three formalin-fixed specimens, with no amplification observed in the remaining. The quantity of amplifiable GAPDH mRNA in the formalin specimens was only 1% of that of the frozen specimens. PMID- 17851965 TI - Influence of nerve branch of origin and extracanalicular extension of the tumor on hearing after middle fossa removal of vestibular schwannoma. AB - CONCLUSION: Neither nerve branch of origin nor extracanalicular (up to 1 cm) extension of a vestibular schwannoma (VS) influence the postoperative hearing outcome in patients operated via a middle cranial fossa (MCF) approach. OBJECTIVE: To test whether the nerve branch of tumor origin and an extracanalicular, up to 1 cm, tumor extension influences hearing outcome after MCF VS surgery. PATIENTS AND METHODS: This was a retrospective case review of 50 patients with postoperative pure-tone audiogram (PTA) performed later than 90 days after surgery. Twenty patients had a superior vestibular nerve (SVN) tumor and 27 patients had an inferior vestibular nerve (IVN) tumor. In three patients the nerve branch of origin of the VS could not be unequivocally determined. Thirty-four patients had a purely intracanalicular (IC) tumor and 16 patients had an extracanalicular extension in the cerebello-pontine angle. The differences between preoperative and postoperative air-conduction pure-tone hearing thresholds at 500, 1000, 2000, 3000, and 4000 Hz were compared between groups using the Mann-Whitney-Wilcoxon test. RESULTS: Neither vestibular nerve branch of origin nor extracanalicular tumor extension (up to 1 cm) caused any significant difference in the degree of postoperative hearing change at any of the tested PTA frequencies. PMID- 17851966 TI - Thirty-year trends in sudden deafness from four nationwide epidemiological surveys in Japan. AB - CONCLUSIONS: The estimated annual number of patients with sudden deafness treated in Japan has increased during the last 30 years, especially in the elderly population. Hypertension and diabetes mellitus could contribute to the etiology of this disorder. OBJECTIVES: To investigate the epidemiological trends of sudden deafness in Japan over the past 30 years by analyzing data from national surveys. MATERIALS AND METHODS: Nationwide epidemiological surveys on sudden deafness were conducted four times by the Research Committee of the Ministry of Health and Welfare in Japan. The first, second, third, and fourth surveys were performed in 1972, 1987, 1993, and 2001, respectively. RESULTS: The estimated annual numbers of patients with sudden deafness treated in Japan were 4000 in 1972; 16,700 in 1987; 24,000 in 1993, and 35,000 in 2001. The average ages of patients at onset were 39.1, 45.4, 49.3, and 51.3 years, respectively. Thus, both the number of patients and the average age of patients with sudden deafness have increased during the past 30 years. Patients with sudden deafness in the fourth survey exhibited hypertension and diabetes mellitus more frequently than did patients in the first survey; this trend was particularly noticeable among elderly patients. PMID- 17851967 TI - Anatomic study of maximum intensity projection of the membranous labyrinth and the internal auditory meatus - MRI scan in 16 Chinese adults. AB - CONCLUSION: Three-dimensional reconstruction of maximum intensity projection (MIP) might document objectively, stereoscopically and directly the minute structures of the membranous labyrinth and internal auditory meatus. In this study, we establish magnetic resonance imaging (MRI) measurement criteria of the inner ear in Chinese adults. OBJECTIVE: The goal of this study was to provide an anatomic basis for otolosurgery and neurosurgery in Chinese adults. MATERIALS AND METHODS: Sixteen healthy volunteer subjects were scanned by a GE-signa 1.5T MRI scanner. All original images were transferred to an MRI workstation and all the structures of the inner ear were reconstructed, rotated at various angles and measured with an MIP program. RESULTS: Anatomic structures of the membranous labyrinth and internal auditory meatus were well demonstrated in MIP images in all volunteers. All inner ear structures including utricle, saccule, cochlear duct, internal auditory meatus and three semicircular ducts produced high intensity signals. PMID- 17851968 TI - Quality of life, drinking to cope, alcohol consumption and smoking in successfully treated HNSCC patients. AB - CONCLUSION: The level of coping by alcohol consumption is broadly associated with level of general quality of life (QoL) in patients with successfully treated head and neck squamous cell carcinoma (HNSCC). OBJECTIVE: The aim of this study was to investigate the association between self-reported level of general coping, drinking to cope (DTC), reported alcohol and tobacco use as well as QoL in successfully treated HNSCC patients. PATIENTS AND METHODS: We employed a cross sectional design. Sample I included all patients <80 years old who had been diagnosed with HNSCC in Western Norway in the period from 1992 to 1997, and who were disease-free in the year 2000. The patients were interviewed at a routine follow-up visit. Sample II included all Norwegian laryngectomized patients. General coping and DTC were assessed by the COPE questionnaire and the QoL was assessed by the EORTC-QLQ (C30/H&N35) questionnaire. Reported level of alcohol consumption was associated with global QoL (r = -0.22) and with DTC (r = 0.31). Reported smoking level was associated with DTC (r = 0.26) and inversely with C30 functional/symptom sum QoL scores (r = -0.31/0.27). Level of DTC was associated with C30 global (r = -0.30) and C30 functional/symptom sum QoL scores (r = 0.31/0.27) and this association was still present after adjustment for gender, age, levels of neuroticism and avoidance coping. PMID- 17851969 TI - Vestibulo-ocular reflex (VOR) preserved in bilateral severe vestibular malformations with internal auditory canal stenosis. AB - A 60-year-old woman, who has suffered from bilateral deafness throughout her life, visited our outpatient clinic. Computed tomography (CT) revealed inner ear malformations, which comprise cochlear aplasia with hypoplastic vestibule in the right ear and a common cavity in the left ear, and narrow internal auditory canals. We performed electronystagmography with caloric stimulation and stimulation of earth-vertical axis rotation (EVAR) or off-vertical axis rotation (OVAR), and studied vestibular evoked myogenic potentials (VEMPs) and vestibular ocular reflex (VOR). Slight horizontal nystagmus was induced by the stimulation of EVAR but not by caloric stimulation. Slight vertical nystagmus was observed during OVAR, whereas the VEMP test elicited no response. The result of horizontal or vertical VOR performed in the dark was almost normal. These findings suggest that VOR can be acquired even with severe malformation of the inner ear whose labyrinthine functions markedly reduce bilaterally until nystagmus is slightly induced by rotation stimulation. PMID- 17851970 TI - The relevance of migraine in patients with Meniere's disease. AB - CONCLUSION: Coexistent migraine affects relevant clinical features of patients with Meniere's disease (MD). OBJECTIVE: Epidemiological studies have shown an association between migraine and MD. We sought to determine whether the coexistence of migraine affects any clinical features in patients with MD. PATIENTS AND METHODS: In this retrospective case-control study of University Neurotology Clinic patients, 50 patients meeting 1995 AAO-HNS criteria for definite MD were compared to 18 patients meeting the same criteria in addition to the 2004 IHS criteria for migraine (MMD). All had typical low frequency sensorineural hearing loss and episodes of rotational vertigo. Outcome measures included: sex, age of onset of episodic vertigo or fluctuating hearing loss, laterality of hearing loss, aural symptoms, caloric responses, severity of hearing loss, and family history of migraine, episodic vertigo or hearing loss. RESULTS: Age of onset of episodic vertigo or fluctuating hearing loss was significantly lower in patients with MMD (mean +/- 1.96*SE = 37.2 +/- 6.3 years) than in those with MD (mean +/- 1.96*SE = 49.3 +/- 4.4 years). Concurrent bilateral aural symptoms and hearing loss were seen in 56% of MMD and 4% of MD patients. A family history of episodic vertigo was seen in 39% of MMD and 2% of MD patients. PMID- 17851971 TI - Breast MRI in the evaluation of locally recurrent or new breast cancer in the postoperative patient: correlation of morphology and enhancement features with the BI-RADS category. AB - BACKGROUND: While breast magnetic resonance imaging (MRI) is a highly sensitive test for detecting breast carcinoma, its specificity is lower, and several methods have been described on how to optimize specificity. PURPOSE: To compare the specificity and sensitivity of the BI-RADS category with the Fischer score in breast MRI for diagnosing cancer in women previously treated for breast cancer. MATERIAL AND METHODS: Women referred for evaluation of possible local recurrence or new breast cancer underwent breast MRI examination. Morphologic and kinetic enhancement characteristics were evaluated. BI-RADS category and Fischer score were assigned for each enhancing lesion and compared using a chi-square test. Sensitivity, specificity,and positive predictive values for 27 morphologic and enhancement characteristics were calculated. Pathologic diagnosis was obtained in all patients with enhancing lesions who had ultrasound or mammographic correlation. In those without correlate, 6-, 12-, and 24-month follow-up breast MRIs were obtained. Interobserver kappa correlation was determined for each variable studied. RESULTS: 34 benign and 32 malignant lesions were identified in 26 of 30 patients. BIRADS category yielded a specificity of 77.1% and a sensitivity of 81.8%. Fischer score had a lower specificity and sensitivity (62.9% and 72.7%, respectively) (P<0.0001). Of the 27 variables studied, >100% enhancement was more sensitive than BI-RADS for malignant lesions. Specificity was highest for rim enhancement (97.1%), but sensitivity was low (24.2%). Interobserver kappa correlation was good for all 27 characteristics(k=0.84), and highest for BI-RADS assessment (k=0.91). CONCLUSION: BI-RADS category in breast MRI had the highest combination of specificity and sensitivity, and the highest interobserver correlation. Fischer score and other morphologic and enhancement features lack sensitivity or specificity and do not have high positive predictive values when analyzed as single independent variables. PMID- 17851972 TI - Extensive coronary thrombus causing full thickness myocardial infarction. AB - A young male presented 22 h following onset of symptoms with an anterior ST elevation myocardial infarction. He was transferred for rescue angioplasty after failing to reperfuse with thrombolytic therapy. On arrival, his symptoms had settled. Following administration of intracoronary abciximab and passage of an angioplasty wire into the distal LAD, extensive thrombus was demonstrated in the left anterior descending artery extending from the ostium to the distal vessel Figure 1(a). Further intervention with attempted thrombectomy was considered but it was postponed pending a viability study because of the risks of displacing thrombus down the circumflex. A cardiac MRI scan with delayed gadolinium hyper enhancement demonstrated the classical appearance of full-thickness infarction in the LAD territory Figure 1(b). No further intervention was therefore indicated. At one-year follow-up, the patient remains free of angina with NYHA Class 1 symptoms of heart failure. PMID- 17851973 TI - Combined percutaneous coronary intervention and atrial septal defect closure in an adult patient. AB - A case of combined percutaneous coronary intervention and ostium secundum atrial septal defect closure in an elderly patient is reported. The procedure was successful and uneventful. The report demonstrates feasibility of combined percutaneous revascularization and intra- atrial shunt closure even in advanced age. PMID- 17851974 TI - Near-normal coronary angiography in a patient, who is entirely asymptomatic 24 years after successful intracoronary thrombolysis for ST elevation myocardial infarction. Follow-up of the historically first Czech intracoronary thrombolysis patient. AB - Extremely long-term follow-up (24 years) of the historically first Czech myocardial infarction patient, treated by intracoronary thrombolysis, is presented. His current coronary angiography confirmed the finding 24 years ago, that this was a case of smoking-induced thrombosis in otherwise healthy coronary arteries. Experience with 76 similar cases among 4093 consecutive coronary angiograms (including 778 done acutely for STEMI) is briefly described. PMID- 17851975 TI - Arrhythmic acute coronary syndrome and anomalous left main stem artery: culprit or innocent bystander. PMID- 17851976 TI - Impact of catheter sizes and intracoronary glyceryl trinitrate on the TIMI frame count when digital angiograms are acquired at lower frame rates during elective angiography and PCI. AB - The TIMI frame count (TFC) is a useful measure of coronary flow. To be widely applicable, the effect of different catheter sizes and the use of intracoronary glyceryl trinitrate (ICGTN) must be determined when films are acquired at lower acquisition rates (12.5 frames/s, f/s). METHODS: We compared 6F versus 5F diagnostic catheters (n = 44), 6F versus 7F diagnostic catheters (n = 45) and 6F diagnostic versus 7F guide catheters (n = 44). In the nitrate angiography group (n = 141), coronary angiography was performed before and after 200 micrograms of ICGTN. In the nitrate percutaneous coronary intervention (PCI) group (n = 48), coronary angiography was performed before and after 200 micrograms of ICGTN after the completion of the elective PCI procedure. RESULTS: The mean difference in the uncorrected TFC using 6F and 5F was 0.02 (95 % CI -0.5, 0.6; P = 0.9); using 6F and 7F diagnostic catheters it was 0.3 (95% CI -0.49, 1.1; p = 0.4); and using 6F diagnostic and 7F guide catheters it was 0.4 (95% CI -2.6, 3.4; P = 0.7) respectively. In the nitrate angiography group, the uncorrected TFC before and after ICGTN was 13.1+/-6.2 and 15+/-7.5 (equivalent to 31.4+/-14.9 and 36+/-2 at 30 f/s), with a mean difference of 1.9 (95% CI 1.3, 2.5; P = or <0.0001). In the nitrate PCI group, the uncorrected TFC before and after ICGTN administration was 9.2+/-3.7 and 10.3+/-4.2 (equivalent to 22.6+/-9.6 and 25.2+/-11 at 30 f/s) respectively with a mean difference between the two injections of 1.2 (95% CI 0.4, 1.9; P = 0.003). CONCLUSION: We have demonstrated that the catheter sizes did not significantly affect the TFC when angiography was performed at 12.5f/s. The use of ICGTN significantly increased the TFC in both normal and diseased coronary arteries. This effect was also observed when ICGTN was administered into the culprit vessels after the completion of the elective PCI procedure. This effect must be considered when investigating the impact of specific treatments or drugs on coronary flow. PMID- 17851977 TI - High prevalence of gastroesophageal reflux in patients with clinical unstable angina and known coronary artery disease. AB - OBJECTIVES: Esophageal disease may mimic acute anginal pain. However, the prevalence of gastroesophageal reflux in the acute setting of patients with clinically unstable angina (UA) pectoris is not known. The aim of this study was to determine the co-existence of coronary artery disease (CAD) and gastroesophageal reflux in UA, and to study the feasibility of esophageal investigation in the chest pain unit. DESIGN: 22 patients with clinical UA and confirmed CAD were monitored by continuous vector cardiography and pH-measurement during 24 h of observation. Symptoms of chest pain and episodes of ischemia and reflux were recorded. RESULTS: 11 patients (50%) showed abnormal gastroesophageal reflux and another three (14%) had an increased number of reflux episodes. pH measurements and esophageal manometry were well tolerated. Few chest pain episodes were recorded during the study period, and no association between chest pain, reflux, and ischemia could be shown. CONCLUSION: Esophageal reflux is common in patients with UA and established CAD. As reflux-related chest pain may imitate angina pectoris, it is clinically important that gastroesophageal examination in patients with UA seems to be feasible and well tolerated in the 'acute setting'. PMID- 17851978 TI - Typical intellectual engagement and cognition in old age. AB - Typical Intellectual Engagement (TIE) comprises the preference to engage in cognitively demanding activities and has been proposed as a potential explanatory variable of individual differences in cognitive abilities. Little is known, however, about the factorial structure of TIE, its relations to socio-demographic variables, and its influence on intellectual functioning in old age. In the present study, data of 364 adults (65-81 years) from the Zurich Longitudinal Study on Cognitive Aging (ZULU) were used to investigate the factorial structure of TIE and to examine the hypothesis that TIE is associated more strongly with crystallized intelligence than with fluid intelligence in old age. A measurement model of a second order factor based on a structure of four correlated first order factors (Reading, Problem Solving, Abstract Thinking, and Intellectual Curiosity) evinced an excellent fit. After controlling for age, sex, and formal education, TIE was more strongly associated with crystallized intelligence than with fluid intelligence, comparable to results in younger persons. More detailed analyses showed that this association is mostly defined via Reading and Intellectual Curiosity. PMID- 17851980 TI - Age and flexible thinking: an experimental demonstration of the beneficial effects of increased cognitively stimulating activity on fluid intelligence in healthy older adults. AB - The disuse hypothesis of cognitive aging attributes decrements in fluid intelligence in older adults to reduced cognitively stimulating activity. This study experimentally tested the hypothesis that a period of increased mentally stimulating activities thus would enhance older adults' fluid intelligence performance. Participants (N=44, mean age 67.82) were administered pre- and post test measures, including the fluid intelligence measure, Cattell's Culture Fair (CCF) test. Experimental participants engaged in diverse, novel, mentally stimulating activities for 10-12 weeks and were compared to a control condition. Results supported the hypothesis; the experimental group showed greater pre- to post-CCF gain than did controls (effect size d=0.56), with a similar gain on a spatial-perceptual task (WAIS-R Blocks). Even brief periods of increased cognitive stimulation can improve older adults' problem solving and flexible thinking. PMID- 17851981 TI - Aging and inhibition of a prepotent motor response during an ongoing action. AB - Inhibitory functions are key mechanisms underlying age related decline (Park & Gutchess, 2000, in: Cognitive aging: A primer. Hove: Psychology Press), yet few studies have investigated their impact on everyday tasks involving action as well as cognition. Using an everyday-based go/no-go task we devised a motor analogy of traditional neuropsychological tests to investigate in 134 older (aged 60-88) and 133 younger adults (aged 20-59) the ability to inhibit a prepotent motor response during an ongoing action. Older adults produced more inhibition failures as expected, but more strikingly inhibitory errors were not all or none; even when the inappropriate response was successfully inhibited, difficulties controlling ongoing movements emerged from as young as people in their 40s. The ability to inhibit therefore does not ensure control of ongoing tasks, and traditional cognitive tests may be unable to detect such difficulties. Furthermore, performance did not covary with education or action speed. Implications for neuropsychological theory and assessing/enhancing functional ability are discussed. PMID- 17851983 TI - Adult age differences in function concept learning. AB - Function concept learning and knowledge use was explored across adulthood. During training older and younger adults predicted an amount of physiological arousal produced as a negative and positive function of a chemical substance. Knowledge use was evaluated with two transfer conditions requiring a switch between contextual contingencies: a relationship inversion, predicting the chemical amount given the physiological arousal, and a change from graphic based to text based stimuli. Older adults were impaired in applying the negative slope concept. However, there was no relative deficit in switching between the negative and positive function slopes or inverting the learned relationship. Our results suggest that age-related differences in relational reasoning tasks vary not only with processing efficiency, but also task related conceptual knowledge. PMID- 17851985 TI - Time of day affects episodic memory in older adults. AB - The neuropsychological test scores of 2030 cognitively normal older adults were examined to evaluate performance patterns as they related to time of day (TOD) at which testing was initiated. Multiple regression analyses were used to examine the association of TOD with scores on seven neuropsychological tests used in the clinical evaluation of dementia. Episodic memory performance was significantly related to TOD, while memory span and verbal fluency were not. Best performance occurred during early morning hours and late afternoon; worst performance occurred mid-day (i.e., noon). These findings may have implications for clinical assessment, the design of research on dementia, and the daily functioning of older adults. PMID- 17851986 TI - Age-related differences in acquisition of perceptual-motor skills: working memory as a mediator. AB - Aging is associated with reduced performance on information processing speed, memory, and executive functions tasks. Although older adults are also less apt in acquiring new perceptual-motor skills, it is unclear whether and how skill acquisition difficulties are associated with age-related general cognitive differences. We addressed this question by examining structural relations among measures of cognitive resources (working memory) and indices of perceptual-motor skill acquisition (pursuit rotor and mirror tracing) in 96 healthy adults aged 19 80 years of age. Three competing structural models were tested: a single (common) factor model, a dual correlated factors model, and a hierarchical dual-factor model. The third model provided the best fit to the data, indicating age differences in simple perceptual-motor skill are partially mediated by more complex abilities. PMID- 17851984 TI - Associative learning over trials activates the hippocampus in healthy elderly but not mild cognitive impairment. AB - The ability to form associations between choice alternatives and their contingent outcomes is an important aspect of learning that may be sensitive to hippocampal dysfunction in memory disorders of aging such as amnestic mild cognitive impairment (MCIa), or early Alzheimer disease. In this preliminary study we examined brain activation using functional magnetic resonance imaging (fMRI) in 12 healthy elderly participants and nine patients with MCIa during an associative learning task. Using a high-field 3.0-Tesla MRI scanner, we examined the dynamic neural response during associative learning over trials. The slope of signal attenuation associated with learning was analyzed for differences between groups within an a priori defined hippocampal region. Results indicated dynamic signal attenuation associated with learning in the healthy elderly sample, but not in MCIa. The absence of an associative learning effect in the MCIa sample reaffirms an important link between the learning difficulties that are commonly encountered in MCIa and the mesial temporal region. PMID- 17851987 TI - Event Timing and age deficits in higher-order sequence learning. AB - Recent studies have reported age deficits in learning sequences that contain subtle sequential regularities (e.g., Curran (1997) Psychological Research, 60(1 2), 24; D. V. Howard et al. (2004) Psychology and Aging, 19(1), 79; Howard, J. H. Jr, & Howard, D. V. (1997). Psychology and Aging, 12(4), 634). This finding is of potential theoretical interest, but the contribution of sequence event timing to this deficit has not been investigated. This study used an alternating serial reaction time task to examine implicit sequence learning in young adults when event timing mimicked that experienced by older adults in previous research. We varied the response-to-stimulus interval directly in Experiment 1 and indirectly by degrading the stimuli to influence response time in Experiment 2. Results indicate that these "aged" young adults learned the higher-order sequence structure implicitly, but they learned less than young controls and more than old adults on some measures of implicit learning in both experiments. In addition, these two different experimental manipulations produced distinct patterns of deficits despite having nearly identical effects on event sequence timing. These findings suggest that event timing alone cannot explain the age deficits observed in high-order implicit sequence learning. PMID- 17851989 TI - HIV vaccine preparedness studies in the organization for economic co-operation and development (OECD) countries. AB - HIV vaccine development remains an urgent priority. This article is a systematic review of HIV vaccine preparedness studies in the high-income 30 Organization for Economic Co-operation and Development countries, to identify factors important for HIV vaccine trial development in injection drug users (IDU), men who have sex with men (MSM), and women at heterosexual risk (WAHR) across these countries. Of 27 articles we identified, willingness to participate (WTP) was assessed in eight studies involving IDU, 11 involving MSM, and one involving WAHR. WTP ranged in IDU at 41-86%, MSM at 23-94%, and in WAHR, it was at 81%. Studies reported recruitment of high-risk individuals. Retention was assessed in eight studies involving IDU, five involving MSM, and three involving WAHR. IDU were retained at a range of 3-98%, MSM at 70-95% and WAHR at 67-92%. This review provides an in depth summary of HIV vaccine preparedness studies that were conducted in the Organization for Economic Co-operation and Development countries. PMID- 17851990 TI - Sexual dysfunction in HIV-positive men is multi-factorial: a study of prevalence and associated factors. AB - To establish the prevalence of sexual dysfunction amongst HIV-positive men and to determine the factors associated with dysfunction we conducted a cross-sectional study in seven European HIV treatment centres. Data on medical history, antiretroviral treatment and laboratory results were collected by interview and case record review. Sexual function was evaluated by the participant self completion of a questionnaire based on the International Index of Erectile Function (IIEF) 711/929. Seventy-seven percent of participants returned the questionnaire. Data from 668 (72%) respondents were included. Thirty-three percent (95%CI: 29.4-36.5%) had moderate/severe erectile dysfunction (EDF) and 24% (95%CI: 20.9-27.3%) had moderate to severe impairment of sexual desire. Variables significantly associated with EDF in multivariable analysis were older age (greater than 40 years), heterosexual status, non-alcohol drinking status, depression, antidepressants, psychotropic medications and duration of ARV therapy. Low sexual desire (LSD) was associated with older age (greater than 40 years), depression and black African ethnicity. We establish that EDF and LSD are common in both ARV naive and ARV experienced, HIV-positive individuals. Erectile dysfunction was associated with long duration of ARV treatment, with a significantly increased risk of dysfunction in the quartile with the longest period of exposure. No significant association was seen with specific classes of anti-retrovirals. Older age, and depression were the variables most consistently associated with both EDF and LSD. PMID- 17851991 TI - Sexual practices of church youths in the era of HIV/AIDS: playing the ostrich. AB - The church could be a powerful force for social and behavioural change, particularly in the current efforts to combat the HIV/AIDS pandemic. Anecdotal evidence suggests that church youths are sexually active but few studies have documented the sexual practices of these youths. We looked at the sexual practices of 341 youths in two churches in southern Nigeria. Sixty-five percent were sexually experienced; age at first sexual intercourse for males was seven years and eight years for females. By 19 years of age, 42% of the females and 44% of the males had become sexually active. In the 12 months preceding the study, 19% of the sexually experienced youths abstained from sex, 30% had one sexual partner and 28% had more than one sexual partner; 60% had used condoms 24% of whom used them always. These results suggest that sexual practices of committed church youths might be similar to those of youths in the wider society. More might be achieved by a more pro-active engagement of the church in young people's sexual and reproductive health matters. PMID- 17851992 TI - Contexts of condom use and non-condom use among young adolescent male perpetrators of dating violence. AB - The purpose of this study was to examine qualitatively the context of and reasons for condom use and non-use among adolescent male perpetrators of dating violence. Semi-structured anonymous interviews were conducted with 19 adolescent males recruited from intervention programs for adolescent perpetrators of dating violence. Interviews included questions about dating violence perpetration, sexual relationships and risk behaviors. Interviews were analyzed using a content analysis approach and coded to examine boys' condom use and non-use behaviors and contexts. Participants (n=19) were aged 17-21 years and were predominantly white (n=9; 47%) or black (n=4; 21%). Half (n=10; 53%) indicated four or more sex partners in the past three months; half (n=10; 53%) reported no or inconsistent condom use in the past three months. Qualitative findings from this study revealed condom use in high-risk casual sex encounters, including 'trains' (1-2 girls having sex with several boys sequentially). Non-use of condoms was more common in steady, often abusive, relationships, although boys reported sexual infidelity in these relationships. These results indicate that non-use of condoms is occurring among adolescent male perpetrators of dating violence, particularly in the context of their steady relationships and despite reports of very high risk sexual activity including sexual infidelity, involvement in 'trains' and multiple sex partners. Sexual health interventions integrated with dating violence and sexual assault prevention efforts and tailored to adolescents are needed. PMID- 17851993 TI - Skinning the goat and pulling the load: transactional sex among youth in Dar es Salaam, Tanzania. AB - Transactional sex has been associated with risk of HIV infection in a number of studies throughout sub-Saharan Africa. Urban young women are economically vulnerable and at heightened risk of HIV infection in Tanzania; yet there are few studies that have explored relationship dynamics, including transactional sex, in this setting. This paper sheds light on the broader context of sexual relationships among youth at risk for HIV, how transactional sex plays out in these relationships, and how the transactional nature of relationships affects women's risk for HIV. We conducted 60 in depth interviews and 14 focus group discussions with young men and women, 16-24 years old, in Dar es Salaam, Tanzania. These data guided the development of a community based HIV and violence prevention intervention for young men. Youth described the exchange of sex for money or other material goods in all types of sexual relationships. While the exchange was explicit in casual relationships, young women voiced material and monetary expectations from their committed partners as well. Young men described their pursuit of multiple partners as sexually motivated, while women sought multiple partners for economic reasons. Young men were aware of the expectations of material support from partners, and acknowledged that their ability to provide for a partner affected both the longevity and exclusivity of their relationships. Youth described a deep mistrust of the motivations and commitment of their sexual partners. Furthermore, young women's financial dependence on men impacted their ability to negotiate safe sexual behaviors in both casual and committed relationships. Programs designed to reduce HIV risk among Tanzanian youth need to take into account the transactional component of sexual relationships and how such exchanges differ according to partner type. PMID- 17851994 TI - Patient preferences among third agent HIV medications: a US and German perspective. AB - The objective is to assess patient preferences for attributes associated with third agent HIV medications, including fosamprenavir/ritonavir (FPVr), fosamprenavir (FPV), lopinavir/ritonavir (LPVr), atazanavir (ATZ), and efavirenz (EFV). Subjects with HIV were recruited in the US and Germany to complete a computerized adaptive conjoint survey that assessed 13 attributes, including moderate to severe side effects, regimen convenience, drug resistance and efficacy. Literature on the target third-agent HIV drugs was used to identify percentage risk and severity level descriptions for each attribute. The derived preference (utility) weights for each attribute level informed the calculation of relative importance estimates for each attribute and the desirability of combinations of attributes matching the respective target third agents. The analysis included 288 HIV-positive participants (US: 132; Germany: 156), 205 of whom were treatment-experienced and 83 of whom were treatment-naive. Of the 13 medication attributes evaluated, developing drug resistance, the risk of lipodystrophy, the risk of gastronitestinal side effects (diarrhoea, nausea and vomiting) and regimen convenience had the greatest impact on preferences. The profile based on FPVr was most preferred. Differences in the risk of developing drug resistance, risk of lipodystrophy, risk of gastrointestinal side effects and regimen convenience would likely be most influential in the perceived relative value of a third-agent medication. Physicians may wish to consider these features, especially when discussing HIV treatment options with their patients. PMID- 17851995 TI - Sex, condoms, gender roles, and HIV transmission knowledge among adolescents in Leon, Nicaragua: implications for HIV prevention. AB - There are few peer-reviewed studies of HIV/AIDS-related knowledge, attitudes, beliefs and practices among adolescents in Central America. A population-based cross-sectional survey was conducted among 246 adolescents in Leon, Nicaragua, where there is reason for concern about a rise in HIV infections. In many respects, Leon adolescents were typical of those in other Latin American countries, with a mixture of correct and incorrect knowledge about transmission of HIV and sexually transmitted infections, a higher proportion of males than females reporting having had sex or using condoms, and inconsistent condom use. While some sexual attitudes conformed to the ideology of machismo, others did not, providing an opening for prevention interventions. Some dimensions of HIV/AIDS stigma were high, and most adolescents disapproved of same-sex sexual behaviour. Intervention against homosexuality-related stigma is particularly urgent because a concentrated HIV epidemic may be emerging in Nicaragua among men who have sex with men. Personal religious beliefs did not appear to pose a barrier to condom use. In a multivariate model, being out of school was a significant correlate of having had sex and of insufficient HIV/AIDS-related knowledge. Accordingly, HIV prevention interventions must reach adolescents both in and out of school. A multi-component approach to prevention is needed, including programmes based in schools, communities, the mass media and health facilities. PMID- 17851996 TI - Cost-effectiveness of clinical interventions for AIDS wasting. AB - Economic studies of HIV/AIDS interventions are important for providing cost effective care. This paper presents a costeffectiveness study of a three-arm clinical trial conducted at Tufts University School of Medicine/New England Medical Center in Boston, Massachusetts that treated 50 patients with AIDS wasting from March 1998 through January 2001. This study compared the costs and impacts of a nutritional counseling intervention alone (NC arm), the nutrition intervention with oxandrolone (OX arm), and the nutrition intervention with progressive resistance training (PRTarm) for the treatment of AIDS wasting. The cost of each intervention was derived for both the three-month clinical trial and a six-month estimated community model (ECM), its projected adaptation to community-based medical care. The cost determination involved obtaining and multiplying unit economic costs and quantities expended of each resource within each study arm. The ECM average cost per client in the cost-effectiveness analysis incorporated both institutional and societal perspectives. The costeffectiveness analysis compared the cost of each intervention to its quality adjusted life-year (QALY) gain (Zeckhauser and Shepard, 1976). From a societal perspective, for the NC arm, the cost per client totaled US dollars 983 for the actual and US dollars 596 under the ECM. For the OX arm, the cost per client totaled US dollars 3,772 for the actual study and US dollars 3,385 under the ECM. For the PRT arm, the cost per client totaled US dollars 3,189 for the actual study and US dollars 2,987 under the ECM. Under the societal perspective the cost per QALY was US dollars 55,000 (range: US dollars 51,000 to US dollars 83,000) for the NC arm, US dollars 151,000 (range: US dollars 149,000 to US dollars 171,000) for the OX arm, and US dollars 65,000 (range: US dollars 44,000 to US dollars 104,000) for the PRTarm. When using only an institutional perspective, the cost per QALY was US dollars 45,000 (range: US dollars 42,000-US dollars 64,000) for the NC arm, US dollars 147,000 (range: US dollars 147,000 to US dollars 163,000) for the OX arm, and US dollars 31,000 (US dollars 21,000 to US dollars 44,000) for the PRTarm. This paper shows that cost and cost-effectiveness analyses can be adapted to a community setting by combining information from community practice and costs with data from a randomized trial. Compared to other AIDS treatments, such as highly active antiretroviral therapies, all three interventions were affordable, but their cost-effectiveness was intermediate. Oxandrolone was the least cost effective of the interventions, even compared to nutrition alone, as it included similar or somewhat greater costs for less of an increase in quality of life. PRT was the most cost-effective treatment for AIDS wasting, particularly from an institutional perspective. Third party payers should consider coverage of PRT. PMID- 17851997 TI - Validation of the HIV/AIDS Stigma Instrument - PLWA (HASI-P). AB - This article describes the development and testing of a quantitative measure of HIV/AIDS stigma as experienced by people living with HIV/AIDS. This instrument is designed to measure perceived stigma, create a baseline from which to measure changes in stigma over time, and track potential progress towards reducing stigma. It was developed in three phases from 2003-2006: generating items based on results of focus group discussions; pilot testing and reducing the original list of items; and validating the instrument. Data for all phases were collected from five African countries: Lesotho, Malawi, South Africa, Swaziland and Tanzania. The instrument was validated with a sample of 1,477 persons living with HIV/AIDS from all of the five countries. The sample had a mean age of 36.1 years and 74.1% was female. The participants reported they knew they were HIV positive for an average of 3.4 years and 46% of the sample was taking antiretroviral medications. A six factor solution with 33 items explained 60.72% of the variance. Scale alpha reliabilities were examined and items that did not contribute to scale reliability were dropped. The factors included: Verbal Abuse (8 items, alpha=0.886); Negative Self-Perception (5 items, alpha=0.906); Health Care Neglect (7 items, alpha=0.832); Social Isolation (5 items, alpha=0.890); Fear of Contagion (6 items, alpha=0.795); and Workplace Stigma (2 items, alpha=0.758). This article reports on the development and validation of a new measure of stigma, HIV/AIDS Stigma Instrument - PLWA (HASI-P) providing evidence that supports adequate content and construct validity, modest concurrent validity, and acceptable internal consistency reliability for each of the six subscales and total score. The scale is available is several African languages. PMID- 17851998 TI - Impact on HIV test providers of giving a positive test result. AB - The provision of a positive HIV antibody test result and the direction and support given to the test recipient are critical components of care and prevention. There has been little research that describes what happens in such interactions between recipient and provider. The impact on the test provider of delivering the HIV test result is an important issue to consider. The discomfort experienced by some health providers in giving a positive test result may have adverse effects on the client interaction or may carry over into subsequent client interactions. Utilizing a thematic analysis on interview data from 24 HIV test providers, we describe the impact of delivering a positive test result on HIV test providers, identify the factors that influence this impact, and describe strategies used to manage the impact. As with other health care professionals communicating "bad news,"HIV test providers experience a variety of impacts. While a small number of providers indicated little or no impact of delivering the HIV positive test result because the diagnosis is ''not the end of the world,'' most indicated it was difficult as it was anticipated that the test recipient would (or did) find the news distressing. Several coping strategies were identified. PMID- 17851999 TI - Predictors of workplace sexual health policy at sex work establishments in the Philippines. AB - Based on the literature, we identified manager and establishment characteristics that we hypothesized are related to workplace policies that support HIV protective behavior. We developed a sexual health policy index consisting of 11 items as our outcome variable. We utilized both bivariate and multivariate analysis of variance. The significant variables in our bivariate analyses (establishment type, number of employees, manager age, and membership in manager association) were entered into a multivariate regression model. The model was significant (p<.01), and predicted 42) of the variability in the development and management of a workplace sexual health policy supportive of condom use. The significant predictors were number of employees and establishment type. In addition to individually-focused CSW interventions, HIV prevention programs should target managers and establishment policies. Future HIV prevention programs may need to focus on helping smaller establishments, in particular those with less employees, to build capacity and develop sexual health policy guidelines. PMID- 17852000 TI - Acceptability of tenofovir gel as a vaginal microbicide by US male participants in a Phase I clinical trial (HPTN 050). AB - We studied the acceptability of tenofovir gel among HIV-infected and uninfected men who were exposed to it during vaginal intercourse. The gel was found to be highly acceptable to most men, the large majority indicating they would probably use it in the future if they were concerned about HIV and the product were available. Men liked the gel's transparency and odorless qualities, although reactions to its viscosity were more varied. Men acknowledged women's rights to self-determination concerning HIV-prevention, yet considered that women's covert use of the product was more acceptable in the context of 'one-night-stands' than in stable relationships, for which dialogue on protection measures was preferred. Restrictions to couples' habitual sexual repertoire and the protocol requirement to use condoms resulted in complaints. Microbicide trials that do not require condom use from men who don't typically use them may provide a more accurate assessment of acceptability. Consistent microbicide use may be contingent on its ease of incorporation into typical sexual practices, type of sexual partnership and contextual issues. PMID- 17852001 TI - Condom use behaviours among 18-24 year-old urban African American males: a qualitative study. AB - The purpose of this pilot project was to develop, administer and assess a brief male-focused and behavioural-driven condom promotion programme for young adult African American males in an urban setting. To achieve the aims of this study, linkages with local community centres were initially fostered and both quantitative and qualitative research methods were employed. Based on relevant tenets of the social cognitive theory and the stages of change model, a series of focus groups were conducted among the target population, recruited from non traditional urban settings, to identify and further explore their perceived condom use barriers and facilitators in order to support programme development. Specifically, the topical items addressed those young men's perceptions of sexuality and condom use within three broad contexts: general sexual behaviours, condom use behaviours, and the relationship between condoms and substance use. The focus group discussions were audiotaped and the transcribed data summarized and analysed based on those thematic topics. The findings revealed that significant myths, misconceptions and knowledge gaps exist regarding HIV/STD related prevention, condom promotion and substance use. The findings imply that there is a critical need to develop target group suitable condom promotion programmes in order to successfully promote, foster and sustain condom use among high-risk populations. PMID- 17852003 TI - Antiretroviral therapy in the lives of women of colour with HIV. AB - Non-adherence to antiretroviral medication is associated with adverse patient outcomes. Considerable research and clinical work has focused on issues surrounding patient compliance to prescribed regimens. Few studies have explored the essence of antiretroviral medications in the lives of women of colour with HIV. A qualitative study of HIV-infected women of colour was undertaken in response to the question: What is the role of antiretroviral medication in your life? Taped interviews were conducted with graduate psychology students and commercially transcribed. Transcriptions were analyzed by Spiegelberg's category cluster-theme process by four different reviewers. Three themes were distilled: trust/mistrust, approach/avoidance motivation and 'constantly tethered'. Strategies designed to increase medication adherence may need to consider these basic themes in order to be successful. PMID- 17852004 TI - Determinants and evolution of squamous intraepithelial lesions in HIV-infected women, 1991-2004. AB - This study presents a case-control nested analysis of cervical squamous intraepithelial lesions (SIL) in a cohort of 423 HIV-infected women with registered Pap smears between 1991 and 2004. Data on Pap smear results, CDC HIV classification, CD4 cell count and antiretroviral therapy were prospectively collected. Pap smears were classified using the Bethesda classification. Women had a median of three Pap smears registered in the database. The first Pap smear was registered 0.05). In comparison with patients in Tobago, diabetic patients in Trinidad, irrespective of gender, had significantly higher prevalence of IDF critical components such as raised BP, raised triglycerides and reduced HDL-cholesterol (all, p < 0.001). Thus, while more patients in Trinidad were diagnosed with MetS based on three or four components, more patients in Tobago were diagnosed based on two components (p < 0.001). CONCLUSIONS: There were high prevalence rates of the components of the MetS in both the islands of Tobago and Trinidad. Quantitatively, the aggregation of the components is higher in patients in Trinidad, which constitute greater risk for adverse cardiovascular outcome. Controlling central obesity should be the target in preventing MetS in the two islands. PMID- 17852051 TI - John Bowlby and ethology: an annotated interview with Robert Hinde. AB - From the 1950s, John Bowlby, one of the founders of attachment theory, was in personal and scientific contact with leading European scientists in the field of ethology (e.g., Niko Tinbergen, Konrad Lorenz, and especially Robert Hinde). In constructing his new theory on the nature of the bond between children and their caregivers, Bowlby profited highly from their new approach to (animal) behavior. Hinde and Tinbergen in their turn were influenced and inspired by Bowlby's new thinking. On the basis of extensive interviews with bowlby's colleague and lifelong friend Robert Hinde and on the basis of archival materials, both the relationship between John Bowlby and Robert Hinde and the cross-fertilization of ethology and attachment theory are described. PMID- 17852052 TI - Prediction and selection of vocabulary for two leisure activities. AB - People who use augmentative or alternative communication (AAC) need access to a relevant, socially valid vocabulary if they are to communicate successfully in a variety of contexts. Many people with complex communication needs who utilize some form of high technology or low technology AAC rely on others to predict and select vocabulary for them. In this study the ability of one speech pathologist, nine leisure support workers, and six people with cerebral palsy to accurately predict context-specific vocabulary was explored. Participants predicted vocabulary for two leisure activities - sailing session and Internet cafe - using the blank page method of vocabulary selection to identify the vocabulary items they considered important for each activity. This predicted vocabulary was then compared with the actual vocabulary used in each of the activities. A total of 187 (68%) of the words predicted for the sailing session were used during recorded conversations, with 88 words (32%) not appearing in the recorded samples. During the visit to the Internet cafe only 104 (47%) of the words predicted occurred in the recorded samples, with 117 words (53%) not occurring at all. These results support the need to socially validate any vocabulary in order to ensure that it is relevant and useful for the person using the AAC system. PMID- 17852054 TI - Long-term outcomes for individuals who use augmentative and alternative communication: Part III--contributing factors. AB - In order to improve outcomes for individuals who use augmentative and alternative communication (AAC), it is important to understand what factors contribute to or detract from positive outcomes. Seven young men who had used AAC systems for at least 15 years, their family members, and professionals who had worked with them, participated in the study. Qualitative interviews were used to identify contextual factors that may have contributed (both positively and negatively) to the young men's outcomes. Factors that impeded positive outcomes included: attitude barriers, cultural differences, technological barriers, and service delivery limitations. Contributions to positive outcomes included: community support, parent and family support, personal characteristics, and appropriate and high-quality AAC services. The results are discussed with implications for clinical practice and directions for future research. PMID- 17852056 TI - Intentional communication acts expressed by children with severe disabilities in high-rate contexts. AB - The purpose of this study was to identify the rates of communication expressed by 17 children with severe disabilities in high-rate school contexts while piloting a new coding system for intentional communication acts (ICAs). The following nine characteristics were used when coding ICAs expressed in both child initiated and adult initiated communicative interactions: joint attention, form of communication, use of pause, persistence, repetition, repair, expression of pleasure or displeasure when understood or misunderstood, expression of pleasure or displeasure to communication partner's message, and evidence of comprehension. Children communicated 1.7 - 8.0 ICAs per minute in the highest rate contexts. Nine of the 34 high-rate contexts were speech clinical sessions, six were activities that included eating, 30 were familiar activities, and four were novel activities. PMID- 17852057 TI - Children's ideas for the design of AAC assistive technologies for young children with complex communication needs. AB - This study examined children's preferences and priorities for the design of assistive technologies to enhance communication for children with complex communication needs. Six children without disabilities were provided with drawing and craft materials and were asked to develop low-tech prototypes of inventions to support the communication of a young child who had significant speech and motor impairments. The design process and the inventions were analyzed using qualitative methods. Results showed that the children's inventions differed significantly from the designs of current AAC technologies. Their inventions were not simply speech prostheses; rather, they integrated multiple functions (e.g., communication, social interaction, companionship, play, artistic expression, telecommunications) and provided dynamic contexts to support social interactions with others, especially peers. The children characterized the systems as companions and utilized innovative names, bright colors, lights, transformable shapes, popular themes, humor, and amazing accomplishments to capture interest, enhance appeal, build self-esteem, and establish a positive social image. The systems were easily personalized to reflect the user's age, personality, attitude, interests, and preferences. Re-designing AAC technologies to incorporate these types of functions and features may increase their appeal and make them easier for young children to learn and use. Results are discussed with reference to implications for future research and development. PMID- 17852059 TI - The Psychiatrists Training Initiative: developing an educational framework for international medical graduates in rural psychiatry. AB - OBJECTIVE: The aim of this paper is to outline challenges and responses in providing a holistic approach to designing and delivering education to international medical graduates (IMGs) undertaking the role of consultant psychiatrists in a rural setting. This paper examines processes underpinning the educational framework with consideration to acculturation issues in Latrobe Regional Hospital's (LRH) Psychiatrists Training Initiative. CONCLUSIONS: To engage and encourage consultant psychiatrist IMGs in an Australian rural setting, it is paramount that educational frameworks incorporate strong elements of communication skills, cross cultural communication and language, with focus on the individual and the group as part of the community. PMID- 17852060 TI - Cricketers and mental health concerns. AB - OBJECTIVE: The aim of this paper is to examine cricket history in order to illustrate some of the mental health issues present in Australia through the years. CONCLUSIONS: Mood disorders, suicide, and drug and alcohol issues are among problems that have beset top level cricketers. A range of factors have contributed to the psychiatric problems that cricketers have encountered. Educating players may be a beneficial preventative strategy. PMID- 17852061 TI - No-suicide contracts and no-suicide agreements: a controversial life. AB - OBJECTIVE: In this paper we describe the origins of suicide prevention contracting, identify the historical factors that led to the adoption of the intervention, and describe legal tensions that have emerged during its use. CONCLUSIONS: It would appear that one of the most frequently used clinical interventions for responding to suicidality has established a place in clinical practice without evidence attesting to its efficacy. We develop some propositions about how and why this clinical technique has been able to consolidate its place in mental health practice and, in so doing, suggest that the original technique was able to secure a clinical place without much apparent resistance because of the confluence of a number of emerging theories and community trends. PMID- 17852062 TI - Mental health care for our ageing Australian population. AB - OBJECTIVE: In the context of the National Strategy for an Ageing Australia, the aim of this paper was to highlight some of the challenges for aged mental health services as our population ages. CONCLUSIONS: The demand for greater consumer participation in treatment planning and provision, and the increasing complexity of managing medical and psychiatric comorbidity in our 'old-old' population will be major drivers for improving our models of clinical practice and forging stronger partnerships between the public and private sectors. PMID- 17852063 TI - Towards a developmental framework of consumer and carer participation in child and adolescent mental health services. AB - OBJECTIVE: This paper examines the concept of consumer participation in the context of developmental changes in parent/child relationships and associated differences in the utilization of child and adolescent mental health services. METHOD: Existing definitions and characteristics of mental health service delivery for children and young people are examined to answer the question,"Who is the consumer in the context of clinical services for young clients and their parents, and does this change with the child or young person's developmental stage?". RESULTS: As children, young people and parents utilize services in this area of mental health, the roles of consumer and carer need redefinition to accommodate both young clients and parents as consumers, and parents also as carers. CONCLUSION: The proposed framework addresses the changing roles of parents and young clients from infancy to early adulthood to guide consumer and carer participation strategies. If child and adolescent mental health services are to apply a developmental perspective and engage both young clients and parents as 'consumers', they need to address challenges related to the differences in expectations and capacities of young clients and parents, to the complexity associated with dual roles, and to promoting meaningful participation. PMID- 17852064 TI - Stop Using Stuff: trial of a drug and alcohol intervention for young people with comorbid mental illness and drug and alcohol problems. AB - OBJECTIVE: Substance abuse is a significant problem in the treatment of young people with their first psychosis. This study reports a randomized trial of a brief manualized cognitive behavioural therapy for substance abuse in young people with psychosis. METHOD: Subjects were randomized between the study treatment and a group treated as usual. Treatment was a four to six session brief cognitive behavioural therapy (CBT) intervention developed specifically for this patient group - Stop Using Stuff (SUS). RESULTS: Both groups improved across the trial. However, those exposed to the active treatment improved significantly on measures of the frequency of cannabis and alcohol abuse. CONCLUSIONS: Brief interventions in substance abuse in young people with psychosis can help moderate substance use in this difficult to treat group. PMID- 17852065 TI - Exploration of structure-antifouling relationships of capsaicin-like compounds that inhibit zebra mussel (Dreissena polymorpha) macrofouling. AB - Macrofouling of aquatic man-made structures by zebra mussels (Dreissena polymorpha) poses significant economic burdens on commercial freshwater shipping and facilities utilising raw water. The negative environmental impact of some current antifouling technologies has limited their use and prompted investigation of non-organometallic and non-oxidising antifoulants as possible environment friendly alternatives. The plant-derived natural product capsaicin and 18 other compounds with one or more capsaicin-like structural features were tested for their potential to inhibit zebra mussel byssal attachment at a single high concentration of 30 microM. Of these, three compounds displaying the highest levels of attachment inhibition where selected for further concentration-response testing. This testing revealed that capsaicin (8-methyl-N-vanillyl-trans-6 nonenamide), N-vanillylnonanamide, and N-benzoylmonoethanolamine benzoate all inhibited byssal attachment with potency values (EC(50)) in the micromolar range. None of these compounds were lethal to adult specimens of the water flea, Daphnia magna, at concentrations that inhibited mussel byssal attachment. PMID- 17852066 TI - Species-specific engineered antifouling topographies: correlations between the settlement of algal zoospores and barnacle cyprids. AB - Novel, non-toxic antifouling technologies are focused on the manipulation of surface topography to deter settlement of the dispersal stages of fouling organisms. This study investigated the effect of the aspect ratio (feature height/feature width) of topographical features engineered in polydimethylsiloxane, on the settlement of cyprids of Balanus amphitrite and zoospores of Ulva linza. The correlation of relative aspect ratios to antifouling efficacy was proven to be significant. An increase in aspect ratio resulted in an increase of fouling deterrence for both zoospores and cyprids. The spore density of Ulva was reduced 42% with each unit increase in aspect ratio of the Ulva specific Sharklet AF topography. Similarly, the number of settled cyprids was reduced 45% with each unit increase in aspect ratio. The newly described barnacle specific Sharklet AF topography (40 microm feature height, aspect ratio of 2) reduced cyprid settled by 97%. Techniques have been developed to superimpose the smaller Ulva-specific topographies onto the barnacle-specific surfaces into a hierarchical structure to repel both organisms simultaneously. The results for spore settlement on first-generation hierarchical surfaces provide insight for the efficacious design of such structures when targeting multiple settling species. PMID- 17852067 TI - Use of artificial substrata by introduced and cryptogenic marine species in Paranagua Bay, southern Brazil. AB - Ports are important locations for the introduction of marine species, while marinas and pontoons often serve as secondary habitats for these species. In a marina near Paranagua Port, a major international port in southern Brazil, the encrusting community was studied to (i) identify possibly introduced species, and (ii) examine the use of artificial substrata by these species. Samples (20 x 20 cm) were taken from fibreglass floats (boardwalks and boat hulls) and concrete columns. A total of 85 species were found of which 50 were classified into three categories: four introduced, 33 cryptogenic and 13 native. The introduced species were the hydrozoan Garveia franciscana (on floats, boats and submerged concrete), the polychaete Polydora cornuta (more abundant on floats and submerged concrete) and the barnacles Amphibalanus reticulatus (equally abundant on the three substrata) and Striatobalanus amaryllis (only on floats and submerged concrete). Organisms were most abundant on floating boardwalks, while species richness and composition were similar to that on boat hulls (32 and 37, respectively), which are an important vector for intraregional transport. All substrata supported at least three of the four introduced, and many of the cryptogenic species. The proportion of introduced to the total number of species was greater than observed in other ports. This demonstrates that the introduction potential is great in Paranagua Bay, especially considering that this study was restricted to one site and sampled only hard substrata. None of the introduced species has yet been identified as invasive, but all are generalists with respect to substratum, indicating their invasive potential. The ability to colonise stable concrete walls shows that they could also colonise the natural granite rocky substrata in the bay, and the ability to colonise floating surfaces indicate their capability of spreading in the region on the hulls of recreational boats. PMID- 17852068 TI - Effects of coating roughness and biofouling on ship resistance and powering. AB - Predictions of full-scale ship resistance and powering are made for antifouling coating systems with a range of roughness and fouling conditions. The estimates are based on results from laboratory-scale drag measurements and boundary layer similarity law analysis. In the present work, predictions are made for a mid sized naval surface combatant at cruising speed and near maximum speed. The results indicate that slime films can lead to significant increases in resistance and powering, and heavy calcareous fouling results in powering penalties up to 86% at cruising speed. The present estimates show good agreement with results from full-scale ship power trials. PMID- 17852069 TI - Evaluation of techniques used in the assessment of subtidal epibiotic assemblage structure. AB - A comparative study was carried out to evaluate the efficiency of a number of techniques commonly used for assessing the structure of subtidal epifaunal communities. Assessments were made of the epifaunal assemblages fouling two substrata: concrete and PVC plastic. Where possible, each technique was undertaken in three ways, namely, in situ underwater, in the laboratory and using image analysis on photographs taken in situ. Comparisons were also made of biomass estimates made on samples taken in situ and in the laboratory. All method and technique combinations assessed detected differences in the epibiotic communities associated with the two fouling substrata. Sampling in situ, in the laboratory and using image analysis gave similar estimates of percent cover. However, there were significant differences in measurements made for most taxa with respect to abundance and frequency counts depending on how the technique was carried out. Laboratory-based sampling of abundance and frequency counts and biomass determinations, rather than in situ or image-analysis based sampling, are recommended for use in future studies of epifaunal fouling. PMID- 17852070 TI - Mini review: hydrodynamics of larval settlement into fouling communities. AB - Flowing water delivers planktonic larvae to surfaces, but also dislodges them. This paper reviews experiments in the field and in laboratory flumes, as well as mathematical models, which have revealed how the interaction of ambient water motion with a developing fouling community affects larval settlement. Although mean current velocities across fouling communities in harbours are low, instantaneous velocities can be much higher due to turbulence and to the velocity oscillations of wind chop and ship wakes. As a fouling community develops, its topography becomes more complex and the range of flow microhabitats on the spatial scale of larvae increases. In spite of the prevalence of waves in shallow coastal habitats, and in spite of the importance to settlement of the fine-scale instantaneous velocities encountered by larvae, most studies of flow effects on larval settlement have focused on unidirectional currents and on temporally- and spatially-averaged aspects of the flow. PMID- 17852071 TI - Enzyme-based antifouling coatings: a review. AB - A systematic overview is presented of the literature that reports the antifouling (AF) protection of underwater structures via the action of enzymes. The overall aim of this review is to assess the state of the art of enzymatic AF technology, and to highlight the obstacles that have to be overcome for successful development of enzymatic AF coatings. The approaches described in the literature are divided into direct and indirect enzymatic AF, depending on the intended action of the enzymes. Direct antifouling is used when the enzymes themselves are active antifoulants. Indirect antifouling refers to the use of enzymes to release an active biocide with AF activity. For direct AF, several patents have been granted, and a commercial product has been launched. However, the achievement of an efficient broad-spectrum AF coating based on a single or a few enzymes has not yet been achieved. An indirect AF coating is not yet available commercially. The technology is mainly limited by the instability of substrate supply, whether the substrates are found in the surrounding seawater or in the coating itself. Legislative issues regarding which part(s) of an enzyme system should be regarded as biocidal for product registration purposes are also considered. The above question currently remains unanswered for technologies utilising indirect enzymatic AF. PMID- 17852072 TI - Evaluation of cartilage damage by measuring collagen degradation products in joint extracts in a traumatic model of osteoarthritis. AB - The objective of this work was to investigate whether collagen degradation products in protein extract from joints could provide quantitative information on cartilage damage. Osteoarthritis (OA) was surgically induced in rat knee joints. Joints were isolated 7, 14 and 28 days after surgery for protein extraction and histology. C-terminal telopeptide of type III collagen (CTX-II), CTX-I and hydroxyproline were measured in protein extracts. Matrix metalloproteinase (MMP) 2 and -9 activity was evaluated by gelatinase zymography and joint pathology was visualized by histology and immunohistochemistry. The results showed that levels of CTX-II were significantly increased in anterior cruciate ligament transection (ACLT)-operated compared with sham-operated knee joints on days 7 and 28, whereas the levels of hydroxyproline and CTX-I epitopes showed no difference. MMP activity was slightly increased in ACLT-operated joints. The CTX-II epitope was highly expressed and co-localized to damaged articular cartilage in ACLT-operated joints. We have therefore demonstrated an increased type II collagen degradation in knees after surgical induction of OA, and propose assessment of collagen degradation epitopes as a quantitative measure of cartilage damage. PMID- 17852073 TI - Correlation between two markers of inflammation, serum C-reactive protein and interleukin 6, and indices of oxidative stress in patients with high risk of cardiovascular disease. AB - As evidence of the involvement of inflammation and oxidative damage in pathogenesis of age-related chronic diseases is growing, epidemiologists need to develop measures of both conditions to study their relationships in human populations. One way of searching for appropriate biomarkers is to examine correlations between different inflammatory markers and oxidative indices. We examined cross-sectional correlations between two inflammatory markers, serum C reactive protein (CRP) and interleukin (IL)-6, and three oxidative indices, plasma levels of alpha-tocopherol and beta-carotene, and urinary levels of 2,3 dinor-5,6-dihydro-15-F2t-isoprostane (F2-IsoP), in 60 individuals at high risk of cardiovascular disease. Correlations between the biomarkers were examined graphically and using the Pearson correlation coefficient. No correlation was found between plasma levels of alpha-tocopherol and either of the inflammatory markers. Plasma beta-carotene inversely correlated with IL-6 (r = -0.46, p=0.0002) and CRP (r = -0.41, p = 0.001). Although urinary F2-IsoP did not correlate with IL-6, this biomarker positively correlated with CRP (r = 0.31, p = 0.002). As only urinary F2-IsoP levels have been validated against known oxidative assaults, their positive association with CRP levels is interpreted as evidence of an interconnection between low-level inflammation and oxidative status. Urinary levels of F2-IsoP and serum levels of CRP represent appropriate biomarkers for future studies of inflammation and oxidative status in humans. PMID- 17852074 TI - Biomonitoring of workers cleaning up ammunition waste sites. AB - 2,4,6-Trinitrotoluene (TNT) is an important occupational and environmental pollutant. In TNT-exposed humans, notable toxic manifestations have included aplastic anaemia, toxic hepatitis, cataracts, hepatomegaly and liver cancer. Therefore, it is important to develop protection measures and to monitor workers involved in the clean-up of ammunition sites. Haemoglobin (Hb) adducts of TNT, 4 amino-2,6-dinitrotoluene (4ADNT) and 2-amino-4,6-dinitrotoluene (2ADNT), and the urine metabolites of TNT, 4ADNT and 2ADNT were found in 22-50% of the exposed workers, but not in the control group. The exposed workers were wearing protective equipment. The levels of erythrocytes, haemoglobin, creatinine, serum glutamic pyruvic transaminase and lymphocyte levels were significantly lower in the exposed workers than in the non-exposed workers. The levels of blood urea and reticulocytes were significantly higher in the exposed workers than in the non exposed workers. Headache (26%), mucous membrane irritation (16%), sick leave (18%), lassitude (8%), anxiety (6%), shortness of breath (3%), nausea (5%) and allergic reactions (8%) were reported by the exposed workers. In a further analysis the U-4ADNT levels and the Hb-adduct levels were compared to the blood parameter and the health effects. The blood parameters were not significantly different between the U-4ADNT positive and U-4ADNT-negative group. Headache, mucous membrane irritation, sick leave, lassitude, anxiety, shortness of breath and allergic reactions were statistically not different between the two groups. Also in the workers with Hb-4ADNT adducts no significant negative changes were seen in regards to the changes of the blood parameters or the health effects. According to the results of the present study, it appears that the blood parameter changes and the health effects are more influenced by other factors than by the internal exposure to TNT. PMID- 17852075 TI - Pre-analytical and biological variability in circulating interleukin 6 in healthy subjects and patients with rheumatoid arthritis. AB - Interleukin (IL)-6, a key player in the inflammatory response, may be a useful biomarker in rheumatoid arthritis (RA). The aim was to determine analytical variability, a reference interval in healthy subjects, and long- and short-term variation in serum and plasma IL-6 in healthy subjects and RA patients. An enzyme linked immunosorbent assay from R&D was used for determination of serum and plasma IL-6. The IL-6 concentration did not depend on the type of anticoagulant used or the 3-h time delay between sampling and processing or repeated freeze thaw cycles. The median plasma and serum IL-6 in 318 healthy subjects were 1.3 pg ml(-1) (range 0.33-26) and 1.4 pg ml(-1) (range 0.25-23), respectively. The median coefficient of variation in plasma IL-6 in 27 healthy subjects during 1 month, and repeated after 6 and 12 months were 27%, 31% and 26%, respectively. No significant long-term changes were observed in serum IL-6 over a 3-year period (14%, p = 0.33). Exercise (cycling) increased serum IL-6 in healthy subjects but not in RA patients. In conclusion, circulating IL-6 is stable regarding sample handling and shows little variation over time. Changes in IL-6 concentrations > 60% (2 times the biological variation) are likely to reflect changes in disease activity and not only pre-analytical or normal biological variability. PMID- 17852076 TI - Clinical evaluation of the simultaneous determination of CA 15-3, CA 125 and sHER2 in breast cancer. AB - OBJECTIVE: We investigated serum levels of CA 15-3, sHER2 and CA 125, and their usefulness in the detection of metastatic disease in breast cancer patients. METHODS: The levels of CA 15-3, sHER2 and CA 125 tumour markers were determined in 60 patients, 40 with localized and 20 with metastatic breast carcinoma. The control group consisted of 10 healthy women. RESULTS: We found that, at the time of diagnosis, serum levels of all three tumour markers were elevated in patients with distant metastases, but of minute importance in the detection of any breast cancer. When the data for the individual markers were combined the overall sensitivity of metastases detection with all three markers improved. In this regard, 90% of patients with distant metastases had an increase in serum level of at least one of tested tumour markers. Similar results were obtained using receiver operating characteristic curve (ROC). Moreover, using ROC we defined cut off values for metastasis detection for each of the tested markers. CONCLUSION: Our findings indicate that measurement of CA 15-3 serum values in conjunction with sHER2 and CA 15-3 can increase sensitivity in metastasis detection. PMID- 17852078 TI - Characterization of oxidative stress in blood from diabetic vs. hypercholesterolaemic patients, using a novel synthesized marker. AB - In the present study, we extend our novel concept of designing and using exogenous markers for the characterization of oxidative stress (OS) and OS associated diseases. The aim was to use such a synthetic compound as a tool for studying OS in blood from diabetic and hypercholesterolaemic (Hc) patients. The marker used N-linoleoyl tyrosine (LT) was constructed from tyrosine and linoleic acid (LA); both components are known to be easily oxidized upon exposure to different types of reactive oxygen/nitrogen species (ROS/RNS), and to generate specific oxidized products, depending on the type of oxidants present in vivo. Using the LT probe, we showed that the ratios of oxidized LT to total LT (Ox LT/LT) is significantly higher in blood samples obtained from diabetic patients, than in Hc patients or healthy control subjects. LC/MS analysis revealed that blood from diabetic patients oxidizes the marker with predominant formation of Ox LT hydroperoxide (LT-OOH) and epoxide (epoxy-LT), where the LA moiety is oxidized to hydroperoxide and to epoxide, respectively. Analysis of oxysterol levels in these samples (GC/MS) revealed that the blood of both diabetic and Hc patients contained significantly more oxysterols than blood of control subjects. Consumption of pomegranate juice by diabetic patients for 3 months suppressed their blood capacity to oxidize the LT and similarly also reduced their blood oxysterol/total cholesterol ratio by 93%. The use of an exogenous marker to characterize OS in blood samples yields important information on the extent of OS, and can provide a fingerprint for the early identification of different pathological conditions associated with OS. PMID- 17852077 TI - Metallothionein responses in the Asiatic clam (Corbicula fluminea) after exposure to trivalent arsenic. AB - The main objective of this work was to evaluate arsenic effects on metallothionein (MT) induction by exposing a freshwater Asiatic clam (Corbicula fluminea) to different concentrations of this metalloid. The presence of MT-like proteins was detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis and compared with a standard rabbit MT. In addition, the polarographic response showed good correspondence between standard MT and MT-like curves from C. fluminea, allowing MT quantification. The results show that clams exposed to different concentrations of arsenic are able to induce significant levels of MTs. Although variability was found in MT induction, significant differences in MT levels were found after 28 days of exposure in all treatments in comparison with the controls, suggesting that exposure to arsenic induced MT like proteins in C. fluminea. PMID- 17852079 TI - IFN-gamma promoter gene polymorphism in psoriasis vulgaris. AB - This study was performed to investigate the association between interferon (IFN) gamma single nucleotide polymorphism (SNP) and susceptibility for psoriasis vulgaris. DNA from 78 patients with psoriasis vulgaris (54 patients with type I psoriasis, 24 with type II psoriasis) and 74 healthy volunteers was investigated. IFN-gamma promoter gene SNP in position 874 was evaluated by polymerase chain reaction with sequence-specific primers (PCR-SSP) and the results were compared between a group of psoriatic patients, divided into early onset of psoriasis (type I) and late onset of psoriasis (type II) subgroups, and healthy control subjects. A significant difference in the genotype frequencies between psoriasis patients and healthy controls was found (p < 0.02) and no significant differences were observed analyzing subsets of psoriatic patients (gender, type of disease) also in carriage and allele frequencies. The results suggest that IFN-gamma polymorphism is associated with susceptibility to psoriasis vulgaris. PMID- 17852080 TI - Biomarkers of leukocyte traffic and activation in the vaginal mucosa. AB - Development of novel vaginal spermicides and anti-human immunodeficiency virus (HIV) microbicides requires careful assessment of their potential to recruit and activate CD4+ HIV-1 host cells in the female genital tract mucosa, two events that facilitate HIV-1 infection. Leukocyte traffic and activation are mediated by proinflammatory cytokines and chemokines, e.g. interleukin (IL)-1, IL-6 and IL-8, which have been detected in vaginal secretions in association with epithelial damage and infections. These proinflammatory mediators, however, have bidirectional, destructive as well as beneficial, effects on the mucosal barrier, and may be counterbalanced by endogenous inhibitors. Here we propose additional biomarkers for the evaluation of compound-induced cervicovaginal mucosal inflammation. Displaying different temporal patterns of detection, the levels of soluble E-selectin, vascular adhesion molecule-1, CD14 and myeloperoxidase in vaginal secretions reflected the mucosal leukocyte reaction to proinflammatory compounds being evaluated for safety in an improved rabbit vaginal irritation model. These biomarkers, which were also detected in human vaginal secretions, may be used to enhance the characterization of mucosal safety of vaginally applied compounds, both in animal as well as clinical studies. PMID- 17852081 TI - Effects of salicylic acid on post-ischaemic ventricular function and purine efflux in isolated mouse hearts. AB - Acetyl salicylic acid (aspirin) is one of the most widely used drugs in the world. Various plasma concentrations of aspirin and its predominant metabolite, salicylic acid, are required for its antiarthritic (1.5-2.5 mM), anti inflammatory (0.5-5.0 mM) or antiplatelet (0.18-0.36 mM) actions. A recent study demonstrated the inhibitory effects of both aspirin and salicylic acid on oxidative phosphorylation and ATP synthesis in isolated rat cardiac mitochondria in a dose-dependent manner (0-10 mM concentration range). In this context, the present study was conducted to determine the effects of salicylic acid on inosine efflux (a potential biomarker of acute cardiac ischaemia) as well as cardiac contractile function in the isolated mouse heart following 20 min of zero-flow global ischaemia. Inosine efflux was found at significantly higher concentrations in ischaemic hearts perfused with Krebs buffer fortified with 1.0 mM salicylic acid compared with those without salicylic acid (12575+/-3319 vs. 1437+/-348 ng ml(-1) min(-1), mean+/-SEM, n=6 per group, p<0.01). These results indicate that 1.0 mM salicylic acid potentiates 8.8-fold ATP nucleotide purine catabolism into its metabolites (e.g. inosine, hypoxanthine). Salicylic acid (0.1 or 1.0 mM) did not appreciably inhibit purine nucleoside phosphorylase (the enzyme converts inosine to hypoxanthine) suggesting the augmented inosine efflux was due to the salicylic acid effect on upstream elements of cellular respiration. Whereas post ischaemic cardiac function was further depressed by 1.0 mM salicylic acid, perfusion with 0.1 mM salicylic acid led to a remarkable functional improvement despite moderately increased inosine efflux (2.7-fold). We conclude that inosine is a sensitive biomarker for detecting cardiac ischaemia and salicylic acid induced effects on cellular respiration. However, the inosine efflux level appears to be a poor predictor of the individual post-ischaemic cardiac functional recovery in this ex vivo model. PMID- 17852082 TI - Very low C-reactive protein in apparently healthy individuals: physiological status or just a reflection of an improved health profile. AB - The objective of our study was to determine whether the very low concentrations of C-reactive protein (CRP) detected by high-sensitivity CRP (hs-CRP) assays that one encounters from time to time in apparently healthy individual represent a physiological status or are just a reflection of an improved general health profile. The concentration of hs-CRP was determined by using the Behring BN II nephelometer. The arbitrary cut-off point of hs-CRP ( or = 2) (346.0 +/- 98.1 vs 260.7 +/- 75.6 micromol/l, p<0.0001). After adjusting for potential confounders, including age, sex, body mass index, blood pressure, lipids and creatinine, we found that SUA levels were independently associated with CFR impairment (beta = -0.417, p<0.0001). We also found that SUA levels were a good predictor of low CFR at the receiver-operating characteristic curve. Area under the curve was 76% (95% CI 0.64-0.88), and SUA levels were significantly predictive of low CFR (p<0.0001). CONCLUSIONS: These results support a role for SUA level as an independent marker of target organ damage in hypertension. PMID- 17852090 TI - Ascending aortic blood pressure waveform is related to coronary atherosclerosis in hypertensive as well as in normotensive subjects. AB - Ascending aortic blood pressure-derived indices were shown to be related to coronary atherosclerosis. However, no study so far has analyzed the relation between ascending aortic pulsatility and the extent of coronary atherosclerosis in normotensives. Therefore, the aim of the present analysis was to assess the relation between central blood pressure-derived indices and the presence and extent of coronary artery disease in patients with and without hypertension. The study group consisted of 821 patients (590 men and 231 women; mean age: 57.3 +/- 10.0 years) with preserved left ventricular function (ejection fraction>50%) undergoing coronary angiography. Hypertension was diagnosed in 639 (77.8%) patients. Ascending aortic blood pressure during catheterization was measured. After multivariate stepwise adjustment the odds ratio (OR) and confidence interval (CI) of coronary artery disease was: pulsatility per standard deviation (SD) OR 1.36 (95% CI 1.01-1.82) in hypertensives and OR 3.96 (1.95-8.07) in normotensives; pulsatility index per SD OR 1.36 (95% CI 1.01-1.85) in hypertensives and OR 4.41 (2.03-9.56) in normotensives. Stepwise linear regression analysis revealed that pulsatility is related to the mean stenosis in the coronary tree in hypertensives (beta = 0.0862, SE = 0.0448, p<0.05) as well as in normotensives (beta = 0.1704, SE = 0.0718, p<0.05). In conclusion, ascending aortic pulsatility is related to the extent of coronary atherosclerosis irrespectively of the presence of hypertension. PMID- 17852091 TI - Awareness of hypertension guidelines in primary healthcare in Poland. AB - The study was aimed at evaluating knowledge of the recent ESH-ESC Guidelines for the management of hypertension among Polish primary care physicians. A validated questionnaire including 30 multiple-choice questions was developed. A representative sample of primary care physicians in Poland was asked to complete the questionnaire. The influence of physicians' characteristics and features of their practices on the quality of the answers was analyzed. The sample included 192 physicians; 125 of them responded to the questionnaire. The mean number of correct answers was 13.4+/-3.1. The best results were observed with regard to treatment (61.2% correct answers), with weaker scores for diagnosis of hypertension (35.2%) and diagnostic tests (31.8%). The results were significantly better among female physicians and physicians working in large towns. The final score was significantly correlated with length of professional experience in practice (r = -0.246, p<0.01). A similar but non-significant correlation with the age of the physician was observed. The study showed that knowledge of hypertension guidelines among primary care physicians in Poland is modest. Educational programs must be especially directed at practitioners with longer primary care experience and those from smaller towns and villages. PMID- 17852092 TI - The pulsatile component of blood pressure: its role in the pathogenesis of atherosclerosis. AB - Pulse pressure (PP) is traditionally believed to increase cardiovascular risk because of an increase in afterload leading to left ventricular hypertrophy. It has also been emphasized that low diastolic blood pressure, being in part responsible for high PP, leads to an impairment of myocardial perfusion with all its adverse consequences. More recently, however, a direct role of pulsatile blood pressure changes in the pathogenesis of atherosclerosis and its complications has become better known. Experimental studies indicate that there is a cause-and-effect type of relationship between the pulsatile component of blood pressure and atherosclerotic process. A significant relationship between the parameters of the pulsatile blood pressure component and the extent of coronary atherosclerosis was also demonstrated. Currently the presence of a bidirectional link between atherosclerosis and PP is commonly postulated, meaning that an increased PP may be both a cause and an effect of atherosclerosis. This may result in a vicious circle wherein the pulsatile blood pressure component induces/enhances the development of atherosclerosis, which in its turn reduces the arterial compliance and enhances pulse wave reflection, thereby leading to an increase in PP. Currently new drug classes are being investigated, which might reduce the pulsatile blood pressure component without changing mean blood pressure level. Their clinical usefulness should become known over the next few years. PMID- 17852093 TI - Master blood pressure variation in office, by self, and in sleep recordings. AB - Variation inherent to each session in any recording situation has to be mastered to obtain informative mean values and differences. Variation due to time trend and unsteady consecutive readings versus inter-arm variations in blood pressure (BP) in the operator-initiated, self-initiated, and sleep recordings were studied by oscillometry. They were small in operator-initiated recordings, increased in self-recordings, and were paramount in sleep. A passive supine patient and simultaneous recordings with cuffs placed in equal horizontal positions are essential conditions for the estimation of a real mean inter-arm difference. The relative variation of pulse pressure (PP), compared with other components, was largest within each situation. Most of the systolic BP (SBP)/diastolic BP (DBP) variation in sleep was due to unequal vertical cuff distances to the heart level. Only sleep PP was independent of the vertical position of cuffs. A plot of inter arm differences can visualize systematic errors in sequences of sleep SBP/DBP. As is well known, every doubling of variation (SD) requires quadrupling the number of independent recordings in order to retain the same size of confidence interval (CI) for a mean value. PMID- 17852094 TI - Awareness, treatment and control of hypertension in Denmark. The Inter99 study. AB - OBJECTIVE: We describe the current status of awareness, treatment and control of hypertension in Denmark and identify predictors for not being optimally treated. METHODS: A population-based sample, the Inter99 study, of 6784 individuals aged 30-60 years completed a questionnaire about lifestyle and risk factors for cardiovascular disease and had a physical examination including at least two blood pressure (BP) measurements. Hypertension was defined as BP >or= 140/90 mmHg or receiving medical treatment for hypertension. Predictors for awareness, treatment and control were analysed in logistic regression models. RESULTS: Nearly 40% were diagnosed with hypertension and more than 60% were not aware of the diagnosis. Half of those aware of the diagnosis did not receive medical treatment and among those who did, only 21% had their hypertension controlled. Only 10% of all persons aware of their hypertension had a BP below 140/90 mmHg. A higher degree of awareness and treatment of hypertension was positively associated with female sex, diabetes, cardiovascular disease, age, contact to general practitioner, healthy diet and increasing body mass index and age. We did not identify predictors for control of hypertension. CONCLUSION: There is a major gap between how hypertensive patients are managed in Denmark and the current treatment goals and recommendations of hypertension. PMID- 17852095 TI - Blood pressure in young adulthood and later disability pension. A population based study on 867 672 men from Sweden. AB - Hypertension is a common chronic condition and can lead to an economic burden for society because of the costs of treatment for high blood pressure and most likely also because of disabilities related to hypertension and its co-morbidities. The aim of this study was to investigate to what extent moderate/severe hypertension in young adulthood increases the risk of becoming a disability pensioner later in life. All Swedish men born 1951 to 1970, who had their systolic blood pressure measured at age 18-19 years in the compulsory military conscription examination were followed from 1990 to 2001 with respect to receiving disability pension. Among 867 672 men (84.3% of the target population), the hazard ratio was 1.33 (95% CI 1.15-1.52) for being granted disability pension because of moderate/severe hypertension compared with men with normal systolic blood pressure after adjustment for conscription centre, body mass index and socio economic conditions in childhood and adulthood. Men with mild hypertension had also an increased hazard ratio (1.09, 95% CI 1.05-1.13) compared with men with normal systolic blood pressure. This study showed that hypertension in young adulthood increased the risk of disability pension in later life. PMID- 17852096 TI - Proportion of isolated clinical hypertension in primary care settings. Comparison of target organ damage in patients with isolated clinical hypertension and patients with sustained arterial hypertension. AB - The aim of this study was to determine the proportion of isolated clinical hypertension (ICH) in newly diagnosed hypertensive patients, and to compare the incidence of target organ damage (TOD) in ICH and sustained hypertension patients. Participants. In a multi-centre study involving 14 primary care centres in Girona, Spain, 140 researchers recruited 214 newly diagnosed hypertensive patients 15-75 years of age, without history of cardiovascular events. Period of study. 2004-6. Method. Self-blood pressure monitoring (SBPM) and ambulatory blood pressure monitoring (ABPM). Evaluation. Anamnesis including blood pressure, physical examination and analysis (creatinine, albumin/creatinine index), electrocardiogram (left ventricular hypertrophy) and retinography (fundus damage). Results. In 129 (60.3%) subjects with sustained hypertension and 85 (39.7%) with ICH, no significant differences were found relative to gender, age, body mass index or blood pressure (155/90 vs 154/90 mmHg, respectively). Cholesterol levels were significant differences between both groups (5.97 mmol/l in sustained hypertension vs 5.64 mmol/l in ICH, p = 0.029). The proportion of ICH was approximately 40%. TOD incidence in sustained hypertensives was similar to that of ICH patients. PMID- 17852097 TI - Rehabilitation of word deafness due to auditory analysis disorder. AB - BACKGROUND: Word deafness refers to an inability to understand spoken words despite intact hearing. In a cognitive approach, word deafness could be explained by a deficiency at the lower perceptive level of the auditory process. The impairment of the auditory analysis system would explain a disorder of identification of speech sounds. Only few studies addressed rehabilitation of central auditory processing and have described therapy focused on phoneme discrimination. OBJECTIVE: To determine whether a specific auditory analysis rehabilitation addressing phoneme discrimination and phoneme recognition may improve oral comprehension and communication. METHOD: A single-case experimental design was used in a 65 year-old woman, with word deafness consecutive to a cerebral infarction which occurred 10 months before. Verbal naming, written expression and written comprehension were normal. Verbal comprehension, repetition and phoneme discrimination and recognition were impaired. In terms of cognitive model of auditory processing, the patient showed impairment of the auditory analysis system affecting verbal comprehension. A computerized rehabilitation of auditory analysis system was carried out in two consecutive tasks: phoneme discrimination and phoneme recognition. Errorless learning therapy was used, with a difficulty hierarchy practised from the easier to the most difficult phoneme and systematic visual cues which were progressively delayed and suppressed. This study tested the efficacy and the specificity of this therapy on the addressed tasks (phoneme discrimination and recognition), related tasks (oral comprehension and repetition), independent tasks (recognition of environmental sounds) and daily life (questionnaire). RESULTS: The phoneme discrimination and recognition impairment was stable over 4 months before therapy. After therapy, phoneme discrimination (p < 0.001) and phoneme recognition (p < 0.0001) were improved. The improvement was specific to verbal sounds recognition, while non verbal sounds recognition was unchanged. An improvement occurred for repetition (p < 0.05) and oral comprehension (p < 0.01). The communication disability decreased (p < 0.05). CONCLUSION: In a case of word deafness, this study demonstrates not only the efficacy of a specific phoneme processing therapy but also its efficacy in the improvement of higher level of cognitive treatment such as oral comprehension and its transfer in daily life. The role of errorless therapy using systematic visual cues and difficulty hierarchy must be underlined. PMID- 17852098 TI - A report of two 'traumatic encephaloceles'; an unrecognized entity. AB - PURPOSE: An unusual complication following severe head trauma in two infants is described. METHOD: 'Acute traumatic encephalocele' or 'extracalvarial herniation' is presented as an entity, different from 'growing skull fracture'. RESULTS: The acuteness of presentation and non-progressive calvarial fracture aperture, along with increasing size of herniated contents is the hall-mark of such pathology. CONCLUSION: Repair of dural defect with a patch after excision of gliosed brain provides satisfactory outcome. PMID- 17852099 TI - Comment on 'Assessment of intra-cranial pressure after severe traumatic brain injury by transcranial Doppler ultrasonography' by Splavski et al. PMID- 17852100 TI - Parental alcohol misuse is a powerful predictor for the risk of traumatic brain injury in childhood. AB - BACKGROUND: Although the positive relationship between parental alcohol use and children's injuries is well established, it is not known whether parental alcohol misuse is a risk factor for traumatic brain injuries (TBIs) of their children and whether subjects with childhood TBI have hazardous drinking habits in adolescence. METHODS: The authors conducted a longitudinal cohort study at Oulu University Hospital. The cohort consisted of 12 058 subjects born in 1966, of which 207 had sustained TBI before the age of 14 years. Data on parental alcohol problems were obtained from the Finnish Hospital Discharge Register and the adolescents' drinking habits were analysed based on a postal inquiry at the age of 14 years. RESULTS: Parental alcohol misuse (RR 1.99, CI 1.19-3.33) and male gender (RR 1.53, CI 1.12-2.08) significantly predicted the risk of childhood TBI. Drinking to intoxication at the age of 14 was significantly associated with parental alcohol misuse (RR 1.62, CI 1.34-1.96), belonging to a one-parent family (RR 1.80, CI 1.61-2.02) and mild TBI (RR 1.67, CI 1.20-2.33). CONCLUSIONS: It was observed that parental alcohol misuse is a major risk factor for TBI in children and drinking to intoxication is a common drinking pattern of adolescents who have sustained TBI in childhood. PMID- 17852101 TI - Spondylodiscitis (disc space infection) associated with negative microbiological tests: comparison of outcome of suspected disc space infections to documented non tuberculous pyogenic discitis. AB - Discitis, an infection of the disc space, is an uncommon diagnosis that, if missed, can lead to spinal deformity and neurological deterioration, although as many as 30% of these patients will have negative microbiological cultures. It was unclear, however, whether the prognosis differed between patients who had positive or negative cultures. A retrospective case note review was carried out to assess the differences in presentation and outcome between these two groups. There were 26 and 43 patients in the negative and positive groups, respectively. Those with a positive culture were more likely to present with pyrexia, have a neurological deficit and not be independently mobile at presentation. The mean CRP recorded at the time of presentation was 96 and 157 in the negative and positive groups respectively (p = 0.004). Similarly, the mean ESR in the positive group was 88 compared with 69 in the negative group (p = 0.02). In conclusion, these patients may be at different ends of a clinical spectrum: those patients with a positive culture having a greater local and systemic inflammatory reaction to the disc space infection. PMID- 17852103 TI - Bryan cervical disc prosthesis: 12-month clinical outcome. AB - A prospective observational clinical study was carried out to determine whether Bryan disc replacement surgery is a suitable alternative to arthrodesis for cervical disc disease. PMID- 17852104 TI - 'Scapula alata' as a consequence of park bench position for a retro-mastoid craniectomy. AB - We report on a patient who developed winged scapula on the contralateral side to the approach for a cerebellopontine tumour excision, an unreported complication following this procedure. We think this was due to damage of the long thoracic nerve in the dependant side, while in the park bench position. PMID- 17852105 TI - Survival of patients with glioblastoma multiforme has not improved between 1993 and 2004: analysis of 625 cases. AB - Glioblastoma is the most common primary brain tumour. The aim of this study was to determine trends in survival over a 12-year period. Survival data were collected retrospectively for 625 patients who had surgery for histologically confirmed glioblastoma between 1993 and 2004 in a single centre. Data including age, sex, preoperative Karnofsky performance score, tumour site, date of surgery, and type of surgical and adjuvant treatment were collected. Overall median survival was 189 days; there was no significant change in survival over 12 years. Multivariate analysis identified the following independent positive prognostic factors: age <60 years (p < 0.0005), Karnofsky score > or = 70 (p < 0.0001), tumour debulking, rather than biopsy (p < 0.001), right-sided lesion (p < 0.05), unilateral tumour (p < 0.05) and radiotherapy (p < 0.0001). Despite neurosurgical advances, the survival of patients with glioblastoma has not changed for more than a decade. Although, overall, glioblastoma has a short survival, our data show that individual patient survival is heterogeneous. PMID- 17852106 TI - Gustatory disturbance due to a cerebellar hemangioblastoma. PMID- 17852107 TI - Long-term follow-up of an infratentorial primary paraganglioma: a case report. AB - We report a case of infratentorial primary paraganglioma for which we have a 10 year incomplete pretreatment clinical and radiological follow-up. Partial surgical removal followed by external radiotherapy resulted in stable disease at 6 years follow-up. We compare our patient's case with similar cases reported in the literature. PMID- 17852108 TI - Treatment of subtotally resected intracranial plasma cell granuloma with steroids: a case report. AB - Primary intracranial plasma cell granuloma (PCG) is a rare form of inflammatory pseudotumour often characterized by non-neoplastic proliferation of plasma cells. The following case indicates a potential role for steroid therapy after subtotal resection. PMID- 17852109 TI - Bi-occipital decompressive craniectomy in refractory post traumatic intracranial hypertension: first report of one case. AB - Decompressive craniectomy (DC) is considered a 'second tier' therapy to control posttraumatic intracranial hypertension refractory to maximal medical treatment. The authors present a case of refractory intracranial hypertension due to diffuse brain swelling and a large (>25 ml) non-surgically-treatable haematoma of the splenium of the corpus callosum successfully treated with bi-occipital DC and augmentative duraplasty. PMID- 17852110 TI - Surgical treatment of aneurysmal subarachnoid haemorrhage in the presence of 24-h endovascular availability: management and results. AB - Endovascular treatment of ruptured intracranial aneurysms increasingly supersedes surgical repair. This study focuses on the management and results in 109 individuals treated surgically when both treatment modalities were available. The management principles were immediate identification of the origin of haemorrhage, early aneurysm repair, minimal brain retraction during surgery and rigorous prevention of secondary brain damage. Predominantly, aneurysms located on the middle cerebral artery and those of the posterior communicating artery were allocated to surgery. Despite of ultra-swift care, aneurysm rebleeds remained a challenge. Although one-third of the patients presented in a poor clinical grade, outcome was good with 87 (80%) of the individuals being independent, 16 (15%) being dependent and six patients (6%) dying. Results of surgical aneurysm repair are good presupposed the untiring ongoing efforts of an inter-disciplinary team of dedicated physicians and nurses. PMID- 17852111 TI - Multiple extra-axial adenocarcinomas mimicking meningiomas: a case report. AB - We present the case of multiple meningeal tumours in the right sphenoid ridge and left parafalcine region. Magnetic resonance imaging disclosed homogenous enhancement. The histopathological examination revealed metastatic adenocarcinoma of both lesions. Metastatic adenocarcinoma should be considered in the differential diagnosis of dural-base lesions and the definitive diagnosis should only be established after the histopathological report. PMID- 17852112 TI - Association of intracranial hypertension without ventriculomegaly and Chiari malformation: a dangerous combination. AB - With the increased use of MRI, tonsillar ectopia, the hallmark of the adult Chiari malformation (ACM) is being more frequently recognized. However, in some cases, the patient's symptoms do not fit with the classical presentation for ACM, but are similar to intracranial hypertension (IH). The latter may be difficult to diagnose in absence of ventricular enlargement. We report a case of ACM and IHWV due to carcinomatous meningitis. PMID- 17852113 TI - Tension pneumoventricle following exposure of shunt chamber. AB - Pneumocephalus is the presence of air within the intracranial vault. Intraventricular pneumocephalus, also known as pneumoventricle is relatively rare and commonly occurs following cerebrospinal fluid diversion procedures. This may occur immediately or be delayed. Although a small amount of pneumoventriculus is asymptomatic and may not require any treatment, when present under tension it needs to be evacuated. We present a case of tension pneumoventricle following exposure of the shunt chamber, which resulted in deterioration of the patients' neurological condition and required evacuation. PMID- 17852114 TI - Fractionated (split dose) radiosurgery in patients with recurrent brain metastases: implications for survival. AB - Radiosurgery is conventionally prescribed for brain metastases with a single dose of radiation. Fractionation has been advocated to improve tumour control. A multivariate analysis of prognostic factors including fractionation has been performed in two consecutive prospective radiosurgery protocols with and without fractionation in order to identify an association, if any, between fractionation and survival. A surgically applied stereotactic head frame was used. Radiosurgery planning was based on a contrast-enhanced CT. Sixty-nine patients underwent the two-fraction regimen and 35 patients had a single treatment. Multivariate analysis showed that the presence of extracranial malignancy, performance status, multiple brain metastases, patient gender and the time from the initial treatment to radiosurgery were independent determinants for survival. Fractionation was also an independent determinant with two-fraction patients surviving a median of 30 weeks versus single fraction patients who survived a median of 16 weeks. Fractionated radiosurgery was associated with improved survival and deserves further investigation. PMID- 17852115 TI - Multiple bilateral sacral perineural cysts unusually distal to the exit foramina. PMID- 17852116 TI - Antitumor necrosis factor (TNF-a) antibodies in the treatment of renal cell cancer. AB - The kinase inhibitors sorafinib and sunitinib have demonstrated significant activity in renal cell carcinoma (RCC), and are now approved by the FDA for use in advanced disease. There still remains a need for novel therapies. Our group were the first to demonstrate activity of thalidomide in RCC, believed to be in part related to the modulation of tumor necrosis factor (TNF-a), a cytokine secreted by RCC with a number of tumor promoting properties. We subsequently conducted a phase II trial of the TNF-a monoclonal antibody infliximab in patients with previously treated advanced RCC. The drug was well tolerated. The response rate was 16% and stability was achieved in a further 16% of patients. Anti-TNF-a therapy may represent an important approach in the treatment of this disease. PMID- 17852117 TI - Dose-intense PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) in advanced pancreatic adenocarcinoma: a dose-finding study. AB - The aim of this study was to assess the maximum tolerated dose (MTD) of an intensified PEFG regimen administered every 14 days to patients with Stage III or metastatic pancreatic adenocarcinoma. Twenty-nine patients received fixed doses of both epirubicin (30 mg/m2) and 5-fluorouracil (200 mg/m2/day on Days 1-14) and of escalating doses of cisplatin and gemcitabine. The MTD was cisplatin 30 mg/m2 and gemcitabine 800 mg/m2. With respect to classical PEFG, intensified regimen potentially improved the dose-intensity of both cisplatin and epirubicin by 50 percent and of gemcitabine by 33 percent, reduced Grade 3-4 haematological toxicity and the number of outpatient accesses. PMID- 17852118 TI - Urticaria and angioedema in renal cell cancer patients treated with IL-2. AB - Interleukin-2 therapy has produced significant improvement in a proportion of patients with renal cell cancer. Dermatologic side effects, such as erythema, have been very common. However, we could find only 2 reports of urticaria in the medical literature. Here, we report 8 patients with renal cell cancer who developed urticaria in association with interleukin-2 therapy. The hives tended to occur at the end of a treatment cycle. Skin tests with IL-2 were negative in two patients. Urticaria did not worsen or consistently occur with repeated courses of interleukin-2 and anaphylaxis was not observed in any patient. Six of the 8 patients previously had urticaria unrelated to IL-2 therapy. PMID- 17852119 TI - To what extent does bilingualism affect children's performance on the NEPSY? AB - Twenty-seven monolingual and 27 bilingual children aged between 6 and 7 years were assessed using the core subtests of the NEPSY, a children's neuropsychological assessment. Bilingual children scored lower than monolingual children in the Language domain and their performance was comparable with the monolingual children in the domains of Attention/Executive Functioning, Sensorimotor, Visuospatial, and Memory. The NEPSY correlates well with measures of academic achievement. It is concluded that the NEPSY is relatively insensitive to cultural factors and appears to be insensitive to bilingualism in the neuropsychological assessment of bilingual children in the United Kingdom. PMID- 17852120 TI - Sense of time and executive functioning in children and adults. AB - A number of patient studies suggest that impairments in frontal lobe functions are associated with disorders in temporal information processing. One implication of these findings is that subjective experience of time should be related to executive functions regardless of etiology. In two experiments, we examined sense of time in relation to components of executive functioning in healthy children and adults. In Experiment 1, children between 8 to 12 years completed six experimental tasks that tapped three components of executive functioning: inhibition, updating, and mental shifting. Sense of time was examined in a duration judgment task in which participants reproduced stimulus durations between 4 to 32 s. In Experiment 2, adult participants completed the time reproduction task under varying concurrent task demands. Both experiments showed selective effects in that time reproduction errors were related to the inhibition and updating, but not to the shifting, components of executive functioning. However, the observed effects were modulated by task demands and age-related differences in cognitive competence. We conclude that individual differences in executive functioning are only weakly related to time reproduction performance in healthy children and adults. PMID- 17852121 TI - Cognitive associations of bimanual haptico-visual recognition in preschoolers. AB - We have investigated the relation between haptico-visual recognition of objects and cognitive tasks in two large samples of preschoolers (n = 534; n = 750). Children aged 6 years completed a cross-modal task in which they have first to haptically explore an object and second to visually recognize it; they also performed phonological, verbal semantic, and visual tasks. For two consecutive years, bimanual haptico-visual recognition was significantly correlated to performance at all the cognitive tasks. The meaning of this relationship is discussed. The study supports the view that haptico-visual recognition tasks should be used as screening tools for early identification of children at risk of learning difficulties. PMID- 17852122 TI - Global and local processing in Williams syndrome: drawing versus perceiving. AB - It has been hypothesized that a local processing bias underlies overall visuospatial impairments in Williams syndrome (WS). However, recent studies have challenged this hypothesis by providing evidence against a local processing bias at the perceptual level. The aim of the present study was to further examine drawing and perceptual skills in children with WS using closely matched hierarchical stimuli. In the drawing task children with WS exhibited a local processing bias. However, no significant preferential bias was found in the perceptual task. This indicates that children with WS do not systematically present a preferential bias for local information. Taken together the findings of the present study suggest that perceptual processing deficits per se are unlikely to explain local processing biases in visuoconstructive tasks often described in people with WS. PMID- 17852123 TI - Predictors of quantitative and qualitative Halstead finger-tapping scores in low socioeconomic status school-age children. AB - Two hundred and thirteen low socioeconomic school-age children in grades 1 through 8 were administered the Halstead Finger Oscillation (or Tapping) Test (HFTT). All children were age appropriate for their grade in school and were not requiring special education services. Hierarchical multiple regression analysis revealed that a composite age/grade classification score, gender, and estimated level of intelligence accounted for approximately 40% of the variability in dominant and nondominant hand scores for these children (multiple R = .627, R(2) = +.393 for the dominant and multiple R = +.607, R(2) = +.368 for the nondominant hand). Only the age/grade level of the child (R(2) = .168) predicted the ability to inhibit adjacent finger movements when performing the HFTT task. Regional normative data for low socioeconomic school-age children are presented. Neurodevelopmental changes in the cortical and subcortical systems underlying finger movement may account for some of the variability observed in children when performing the HFTT. PMID- 17852125 TI - Learning, attention, writing, and processing speed in typical children and children with ADHD, autism, anxiety, depression, and oppositional-defiant disorder. AB - Learning, attention, graphomotor, and processing speed scores were analyzed in 149 typical control children and 886 clinical children with normal intelligence. Nonsignificant differences were found between control children and children with anxiety, depression, and oppositional-defiant disorder. Control children performed better than children with ADHD and autism in all areas. Children with ADHD and autism did not differ, except that children with ADHD had greater learning problems. Attention, graphomotor, and speed weaknesses were likely to coexist, the majority of children with autism and ADHD had weaknesses in all three areas, and these scores contributed significantly to the prediction of academic achievement. PMID- 17852124 TI - Left-right differences on timed motor examination in children. AB - Age-related change in the difference between left- and right-side speed on motor examination may be an important indicator of maturation. Cortical maturation and myelination of the corpus callosum are considered to be related to increased bilateral skill and speed on timed motor tasks. We compared left minus right foot, hand, and finger speed differences using the Revised Physical and Neurological Assessment for Subtle Signs (PANESS; Denckla, 1985); examining 130 typically developing right-handed children (65 boys, 65 girls) ages 7-14. Timed tasks included right and left sets of 20 toe taps, 10 toe-heel alternation sequences, 20 hand pats, 10 hand pronate-supinate sets, 20 finger taps, and 5 sequences of each finger-to-thumb apposition. For each individual, six difference scores between left- and right-sided speeded performances of timed motor tasks were analyzed. Left-right differences decreased significantly with age on toe tapping, heel-toe alternations, hand pronation-supination, finger repetition, and finger sequencing. There were significant gender effects for heel-toe sequences (boys showing a greater left-right difference than girls), and a significant interaction between age and gender for hand pronation-supination, such that the magnitude of the left-right difference was similar for younger, compared with older girls, while the difference was significantly larger for younger, compared to older boys. Speed of performing right and left timed motor tasks equalizes with development; for some tasks, the equalization occurs earlier in girls than in boys. PMID- 17852126 TI - The impact of stimulants on a clinical measure of attention in children with ADHD. AB - The effect of stimulant medication on the attentional functioning of 23 children (8-12 yrs) with attention deficit/hyperactivity disorder (ADHD) was investigated. Significant main effects of medication and TEA-Ch subtests were found, however there was no significant interaction. Planned contrasts showed that stimulants improved performance on the sustained attention, but not the selective or divided attention, subtests. Similar to previous studies, the results indicate that stimulants improve sustained attention in children with ADHD. Significant effects of stimulants on selective and divided attention, however, were not as apparent. Therefore, care must be taken when using TEA-Ch subtests to assess performance change subsequent to stimulant administration. PMID- 17852127 TI - Effect of treatment with stimulant medication on nonverbal executive function and visuomotor speed in children with attention deficit/hyperactivity disorder (ADHD). AB - This study used a novel hidden maze learning test to examine the nature and magnitude of impairment on separable aspects of executive function in 36 children with ADHD. A within-subject analysis of children with ADHD was also conducted to assess cognitive effects of open-label stimulant treatment. Compared to 31 age matched controls, unmedicated children with ADHD were slower and made significantly more errors that were indicative of relative impairment in prepotent response inhibition and ability to "maintain set" while using simple rules to complete the task. Open-label administration of stimulant medication led to faster and more efficient performance, with children with ADHD making fewer perseverative and rule-break errors than when off medication. This instrument might be useful in monitoring treatment response in specific aspects of executive function and in assisting with dose-titration decisions. PMID- 17852128 TI - Motor response inhibition and execution in the stop-signal task: development and relation to ADHD behaviors. AB - The main aim of this study was to investigate the developmental course of motor response inhibition and execution as measured by the stop-signal task in a population-based sample of 525 4- to 12-year-olds. A further aspiration of the study was to enhance the limited knowledge on how the various stop-signal measures relate to ADHD behaviors in a normal sample. We also wanted to contribute to the theoretical understanding of the various stop-signal measures by examining the relations between the stop-signal measures and performance on tasks reflecting other aspects of response inhibition and execution. Our results showed that the ability to inhibit as well as to execute a motor response as measured by the stop-signal task improved with age during childhood. Of specific interest are the findings suggesting that this task captures the development of motor response inhibition in the late preschool years (age 5 years). Both of the inhibition measures derived from the stop-signal task (i.e., SSRT and probability of inhibition) related significantly to teacher ratings of inattention as well as to performance on tasks tapping other aspects of inhibition. The data provided by this study have thus contributed to the scarce knowledge on early development of motor response inhibition, as well as suggested that the stop-signal task may be a valuable tool for capturing deficient motor response inhibition in ADHD behaviors in normal samples. PMID- 17852129 TI - Development of inattention, impulsivity, and processing speed as measured by the d2 Test: results of a large cross-sectional study in children aged 7-13. AB - The development of three aspects of selective attention was studied in 451 Dutch schoolchildren attending second to sixth grade. Selective attention was measured with the d2 Test of attention. The largest age differences were found for processing speed that continued to improve until the sixth grade. Impulsivity, as measured by the percentage of errors of commission, decreased until the fourth grade. Inattention, measured by the percentage of errors of omission, was stable in all grades. Processing speed and impulsivity were correlated with the score on the Attention Problems subscale of the Child Behavior Checklist. These results imply that selective attention continues to develop, at least, until the end of elementary school. The findings are support for a step-wise model of cognitive development (P. Anderson, 2002). PMID- 17852130 TI - How many is enough? Determining optimal sample sizes for normative studies in pediatric neuropsychology. AB - The purpose of this investigation was to determine how confidence intervals (CIs) for pediatric neuropsychological norms vary as a function of sample size, and to determine optimal sample sizes for normative studies. First, the authors calculated 95% CIs for a set of published pediatric norms for four commonly used neuropsychological instruments. Second, 95% CIs were calculated for varying sample size (from n = 5 to n = 500). Results suggest that some pediatric norms have unacceptably wide CIs, and normative studies ought optimally to use 50 to 75 participants per cell. Smaller sample sizes may lead to overpathologizing results, while the cost of obtaining larger samples may not be justifiable. PMID- 17852131 TI - Salience and temporal sequencing of time-related actions in boys with attention deficit/hyperactivity disorder. AB - Twenty-four 8- to 12-year-old boys with ADHD and 24 non-ADHD boys matched on age and IQ viewed an edited, nondialogue portion of a humorous television program to examine performance on a task requiring attention to and recall of temporal information. Participants were required to retell the story as closely as possible, to complete a picture-prompted sequencing task taken from the story, and to identify time-saving actions taken by the central character. Measures were also obtained of the number of prospective, retrospective, or present time related references made and whether participants correctly identified the overarching time theme of the story. Significant group differences in favor of the comparison boys were evident in the total number of actions recalled and the number of events recalled in sequence. When controlling for poorer memory performance in boys with ADHD, however, there was no significant main effect of diagnostic group. A logistic regression analysis controlled for poorer memory performance indicated no significant differences between the number of boys with and without ADHD who correctly identified the overarching time theme of the story. PMID- 17852132 TI - Independence of speed and accuracy in visual search: evidence for separate mechanisms. AB - Data from two studies that tested children's attention using visual search for a series of targets in a complex display and a sustained-attention task waiting for signals in a similar display were subjected to Factor Analysis to explore previous indications that speed and accuracy (the number of false alarms to nontargets) on this task reflect different mechanisms. The two factors identified confirmed the separation of these two measures and also suggested that the speed factor was related to Mental Age, while the accuracy factor was related to ratings of attentional ability. It is suggested that ratings of attentional ability reflect the efficiency of executive functions, displayed in the ability to inhibit responses to nontargets in these tasks, while speed of search is related to processing speed in the nervous system. Therefore intelligence and attentional ability depend on different underlying features of the nervous system. PMID- 17852133 TI - Language outcome after perinatal stroke: does side matter? AB - The goal of this study was to examine structured language skills in children with perinatal strokes. Participants were 28 school-age children with early focal brain lesions (17 with left hemisphere [LH] damage, 11 with right hemisphere [RH] damage), and 57 controls. A standardized test of language (Clinical Evaluation of Language Fundamentals-Revised) was administered. Receptive, Expressive, and Total Language scores, as well as subtest scores, were analyzed. Control participants scored within the normal range, whereas the LH and RH groups scored significantly more poorly than did controls. There were no differences between the LH and RH groups on any of the language scores, and all scores were below the 14th percentile. Within the lesion group as a whole, scores were not related to lesion laterality, site, or severity. Results also were not accounted for by socioeconomic status or IQ. However, children who experienced seizures demonstrated significantly poorer performance than did children who did not experience seizures. Damage to either the LH or RH early in development adversely affects later language abilities, particularly on tasks with structured and complex linguistic demands. Although lesion side has little effect, the presence or absence of seizures is a major contributor to language outcome. PMID- 17852135 TI - Poor readers but compelled to read: Stroop effects in developmental dyslexia. AB - We studied a group of 24 children with dyslexia in second to fifth primary school grades by using a discrete-trial computerized version of the Stroop Color-Word Test. Since the classic Stroop effect depends on the interference of reading with color naming, one would expect these children to show no interference or, at least, less interference than normal readers. Children with dyslexia showed, however, a Stroop effect larger than normal readers of the same age. This suggests that reading, although difficult and slow, is an inescapable step that precedes naming both in poor and in normal readers. PMID- 17852137 TI - Press statement. Breast cancer and hormone therapy: a looking-glass mirror? PMID- 17852138 TI - New hormonal therapies and regimens in the postmenopause: routes of administration and timing of initiation. AB - Since the publication of the Women's Health Initiative (WHI) study followed by the results of the Million Women Study (MWS), the role of hormonal therapy in postmenopausal women has been further challenged. The risks attributed to hormone therapy have been overestimated and the data has been wrongly extrapolated to the whole class of therapies. The trends in postmenopausal hormonal therapy seem now to favor the non-oral delivery routes for both the estrogen and the progestin for women with an intact uterus, based on the assumption that a lesser stimulation of the liver proteins and a neutral metabolic profile would be more favorable in terms of cardiovascular and venous risk. The combination of non-oral administration of estradiol and local delivery of progesterone or a progestin such as levonorgestrel by means of gels, sprays, vaginal rings or intrauterine systems would represent new methods of replacement therapy for the menopausal woman, improving compliance and minimizing the risks of hormone replacement. Several of these systems are either available or in development. Long-term studies on the risk/benefit of various non-oral formulations are certainly warranted. PMID- 17852139 TI - Acupuncture in managing menopausal symptoms: hope or mirage? AB - There is an increased interest amongst women in seeking alternatives for hormone replacement therapy because of their fear of side-effects. It is claimed that acupuncture is effective for curing menopausal symptoms, and to be a safe treatment in the hands of well-trained and qualified practitioners. About one million acupuncture treatments are given in the National Health Service and two million privately each year in England for various indications. However, because its mechanism of action is not fully understood in physiological terms, acupuncture is considered by many clinicians to be of no value. This article reviews the currently available evidence as regards the effectiveness and safety of acupuncture in treating menopausal symptoms. PMID- 17852140 TI - Is osteoporosis in postmenopausal female patients related to previous pregnancies and/or miscarriages? AB - OBJECTIVE: To investigate if osteopenia and osteoporosis in postmenopausal female patients are related to previous pregnancies and/or miscarriages. PATIENTS AND METHODS: We studied 81 postmenopausal female patients, 40 with osteopenia or osteoporosis and 41 without osteopenia or osteoporosis, carefully matched for age (control group). In the two groups, the presence or not of osteopenia, osteoporosis, or both, were analyzed and compared with the number of childbirths and/or miscarriages. RESULTS: Overall, no statistical difference was found among the 40 patients with one, two, three or more than three childbirths and osteopenia or osteoporosis compared with the control group (p=0.5363, p=0.5782, p=0.0763, p=0.1931, respectively). Similarly, no differences were found between the osteopenia/osteoporosis group and the control group in relation to previous one, two, three or more than three miscarriages. When both childbirths and miscarriages were added together (three, four, five, six, more than six), again no statistical difference was found between the osteopenia/osteoporosis group and the control group. CONCLUSIONS: In postmenopausal women, the obstetric history of previous childbirths and/or miscarriages, independent of the number, did not seem to be a risk factor for osteopenia or osteoporosis. PMID- 17852141 TI - Could androgens protect middle-aged women from cardiovascular events? A population-based study of Swedish women: The Women's Health in the Lund Area (WHILA) Study. AB - OBJECTIVE: The aim of this analysis was to delineate perceived associations between androgens and cardiovascular events in perimenopausal women. DESIGN: A cross-sectional, population-based study of 6440 perimenopausal women aged 50-59 years, living in Southern Sweden. In all, 461 (7.1%) women were premenopausal (PM), 3328 (51.7%) postmenopausal without hormone therapy (HT) (PM0) and 2651 (41.2%) postmenopausal with HT (PMT). For further comparisons, 104 women (1.6%) who reported cardiovascular disease (CVD) were studied in detail; 49 had had a myocardial infarction, 49 a stroke and six women both events. For each woman with CVD, two matched controls were selected (n=208). RESULTS: In the matched controlled series, androstenedione levels were lower (p<0.005) in cases. Cases with hormone therapy had also lower testosterone levels than matched controls (p=0.05). In the total cohort, by using multiple logistic regression analyses, testosterone was positively associated with low density lipoprotein cholesterol (p<0.001) and high density lipoprotein cholesterol (HDL-C) (p<0.001) in all women, but negatively associated with levels of triglycerides in both the PM0 (p<0.001) and PMT (p<0.001) groups. Androstenedione levels were positively associated with HDL-C (p<0.05) and negatively with triglycerides (p<0.05) in the PM group. CONCLUSION: Women with cardiovascular disease had lower serum androgen levels, particularly women using hormone replacement therapy, even when controlled for lipids and other potential risk factors. PMID- 17852142 TI - Menopause alters the metabolism of serum serotonin precursors and their correlation with gonadotropins and estradiol. AB - OBJECTIVE: Tryptophan, the serotonin (5-HT) precursor, is circulating in blood in both free (FT) and protein-bound forms. The free form crosses the hematoencephalic barrier and is converted into 5-HT. During the fertile years, tryptophan levels are negatively correlated to gonadotropin concentrations. The present study aims to evaluate the correlation between circulating tryptophan, gonadotropin and estradiol (E2) levels postmenopause. METHODS: Serum levels of total tryptophan (TT, free + protein-bound) and FT, and plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), and E2 were determined in 15 postmenopausal women and 15 cycling women during follicular (days 7-10), periovulatory (days 13-16) and luteal (days 21-24) phases of the menstrual cycle. Data were analyzed by ANOVA, linear correlation coefficients and hierarchical cluster analysis of variables. RESULTS: TT, but not FT, levels were significantly (p<0.05) higher in postmenopausal (12.07+/-0.40 microg/ml) than fertile women in the periovulatory period (10.46+/-0.36 microg/ml). In postmenopausal women, there was no significant correlation between TT and FT, nor between these tryptophan forms and gonadotropins, but only between FT and E2. Cluster analysis showed that the main cluster composed by FSH-LH-TT-FT observed in fertile women was absent in postmenopause, since both serum tryptophan forms were distant from gonadotropins. CONCLUSION: High TT levels circulate in postmenopausal women, with lack of correlation between TT and FT, and FT/TT and gonadotropins. Since estrogens play a pivotal role on central 5-HT metabolism, estrogen deprivation may alter the brain tryptophan utilization for 5-HT synthesis and its relation to gonadotropin release. PMID- 17852144 TI - Changes in activity level in women aged 40-80 years. AB - OBJECTIVES: The purpose of this study was to report habitual physical activity levels in women and document the change in level of activity and factors affecting this change over a 5-year period. METHODS: A 5-year prospective cohort design was used. Women aged 40-80 years, living independently in the community, were recruited via the electoral role. The effects were investigated, first, of age, activity level, history of falls, number of co-morbidities and medications, body mass index and stability at baseline on change in activity level and, second, change in these demographics on activity level over the study period. RESULTS: Data from 459 women who completed our study are reported. Only activity level and body mass index at baseline significantly affected change in activity level (p<0.000). Change in activity level was not influenced by change in demographics over the study period. The forties and fifties cohorts accounted for the baseline body mass index effect on activity change (p<0.04). In the forties cohort, number of medical conditions at base line (p<0.03) and, in the sixties cohort, increase in number of medical conditions (p=0.011) affected activity level change. CONCLUSIONS: Activity level at baseline and body mass index in younger women were most likely to affect change over time. Being unsteady or having already fallen did not stimulate change. PMID- 17852143 TI - The differential effect of estrogen, estrogen-progestin and tibolone on coagulation inhibitors in postmenopausal women. AB - OBJECTIVES: Hormone therapy increases the risk of venous thromboembolism, possibly through a negative effect on coagulation inhibitors. The aim of the study was to assess the effect of conjugated equine estrogens alone or in combination with medroxyprogesterone acetate, low-dose 17beta-estradiol combined with norethisterone acetate and tibolone on inhibitors of coagulation. METHODS: Two hundred and sixteen postmenopausal women received orally either conjugated equine estrogens 0.625 mg (CEE, n=24) or tibolone 2.5 mg (n=24) or CEE+medroxyprogesterone acetate 5 mg (CEE/MPA, n=34) or 17beta-estradiol 1 mg+norethisterone acetate 0.5 mg (E2/NETA, n=66) or no therapy (control, n=68) for 12 months. Plasma antithrombin, protein C and total protein S were measured at baseline and at 12 months. RESULTS: CEE, CEE/MPA and E2/NETA treatment were associated with a significant decrease in antithrombin levels (CEE: baseline 235.6+/-47.6 mg/l, follow-up 221.3+/-48.3 mg/l, p=0.0001; CEE/MPA: baseline 251.1+/-38.6 mg/l, follow-up 225.0+/-42.6 mg/l, p=0.009; E2/NETA: baseline 257.1+/-59.4 mg/l, follow-up 227.1+/-50.4 mg/l, p=0.007; tibolone: baseline 252.6+/-62.4 mg/l, follow-up 261.9+/-59.1 mg/l, p=0.39). Protein C decreased significantly in the CEE and CEE/MPA groups (CEE: baseline 3.64+/-1.17 mg/l, follow-up 2.48+/-1.47 mg/l, p=0.004; CEE/MPA: baseline 3.24+/-1.23 mg/l, follow up 2.61+/-1.38 mg/l, p=0.001; E2/NETA: baseline 3.24+/-1.10 mg/l, follow-up, 3.15+/-1.11 mg/l, p=0.08; tibolone: baseline 3.26+/-1.25 mg/l, follow-up 3.09+/ 1.32 mg/l, p=0.37). Protein S decreased significantly only in the CEE/MPA group (CEE: baseline 19.4+/-2.76 mg/l, follow-up 18.0+/-2.45 mg/l, p=0.56; CEE/MPA: baseline 18.4+/-3.42 mg/l, follow-up 14.5+/-3.43 mg/l, p=0.005; E2/NETA: baseline 19.0+/-3.11 mg/l, follow-up 19.5+/-3.43 mg/l, p=0.18; tibolone: baseline 18.5+/ 3.09 mg/l, follow-up 18.0+/-4.09 mg/l, p=0.32). CONCLUSIONS: Estrogen and estrogen-progestin therapy are associated with a reduction in coagulation inhibitors, the extent of which depends on the regimen administered. Tibolone appears to have no effect on inhibitors of coagulation. PMID- 17852145 TI - Uterotropic effects of dietary equol administration in ovariectomized Sprague Dawley rats. AB - AIM: The aim of the present study was to evaluate the uterotropic effects of the administration of dietary equol, a metabolite of soy-derived daidzein or formononetin present in red clover, in an ovariectomized rat model of menopause. METHOD: Two doses of racemic equol were used (50 mg/kg of chow and 400 mg/kg of chow) and the results were compared with two doses of estradiol-3 benzoate (E2B) (4.3 mg/kg of chow and 17.3 mg/kg of chow). After 3 months, animals were sacrificed and the uteri were removed, weighed and paraffin-embedded for morphometrical and immunohistochemical evaluation. The expression of selected uterine estrogen-responsive genes was also measured using real-time reverse transcription-polymerase chain reaction. RESULTS: Compared to controls, uterine weights in animals treated with high-dose equol were significantly higher, presented histologic features of mild estrogenic stimulation and had greater epithelial height and thickness of the uterine stroma and myometrium. Staining for the presence of the proliferating cell nuclear antigen (PCNA) also showed a greater prevalence of the PCNA-positive cells in the uterine stroma in animals treated with high-dose equol. Conversely, the percentage of PCNA-positive cells in the uterine epithelium was lower compared to the controls. Dietary high-dose equol treatment also increased significantly levels of uterine insulin-like growth factor 1, progesterone receptor and complement protein 3 mRNA. Although statistically significant, all these effects were, however, lower in magnitude compared to the effects of low- and high-dose E2B treatment. Low-dose equol did not have any effects on the above-studied parameters. CONCLUSION: Long-term high dose dietary equol administration to ovariectomized rats exerts uterotropic effects at the cellular and molecular level which question the safety of uncontrolled and unlimited consumption of soy or red clover supplements by postmenopausal women with intact uteri. PMID- 17852146 TI - Estradiol, FSH and LH profiles in nine ethnic groups of postmenopausal Asian women: the Pan-Asia Menopause (PAM) study. AB - OBJECTIVES: Significant differences in the prevalence of menopausal symptoms and in lipid profiles have previously been reported for nine ethnic groups of postmenopausal Asian women participating in the Pan-Asia Menopause (PAM) study. Based on these findings, we tested the hypothesis that reproductive hormone profiles differ among the nine ethnic groups under investigation in the PAM study. METHODS: Baseline serum samples from postmenopausal women (n=1020) representing nine ethnic groups were analyzed at a central laboratory by electro chemiluminescence immunoassay methods. Hormone concentrations were measured for estradiol (E2), follicle stimulating hormone (FSH) and luteinizing hormone (LH). RESULTS: The hormone levels for the overall study population (mean+/-SD) were: E2=74.1+/-125.1 pmol/l (n=1015); FSH=81.2+/-31.4 IU/l (n=1013); LH=36.8+/-15.6 IU/l (n=1015). Estradiol levels ranged from 50.0 pmol/l in Chinese women to 106.8 pmol/l in Vietnamese women; FSH ranged from 68.2 IU/l in Korean women to 90.8 IU/l in Malay women; and LH ranged from 30.7 IU/l in Korean women to 44.1 IU/l in Malay women. There was an inverse correlation between log E2 and FSH levels and a positive correlation between FSH and LH levels. The concentrations of E2, FSH and LH were significantly associated with ethnicity after adjustment for age and body mass index. Additionally, the concentrations of all three hormones were significantly associated with body mass index, whereas E2 and LH levels were associated with age, but FSH levels were not. CONCLUSION: The levels of FSH, LH and particularly of E2 differ substantially among ethnic groups of postmenopausal Asian women. The clinical significance, if any, of these differences remains to be investigated. The inverse correlation of E2 and FSH levels suggests that E2 at the postmenopausal state still affects pituitary FSH output. PMID- 17852147 TI - Metabolic syndrome in postmenopausal women: higher prevalence in the Northeastern Region of Brazil than in other Latin American countries and the influence of obesity and socioeconomic factors. PMID- 17852148 TI - Comment on osteonecrosis of the jaws and bisphosphonates. PMID- 17852150 TI - Word juncture behaviours in young children's spontaneous speech production. AB - The present study explores word boundary behaviours in the spontaneous speech of a group of 6 preschool children. Speech collected in play settings is examined for the presence of normal and atypical connected speech behaviours, and to identify specific instances of open and close word juncture behaviours. The findings suggest that developmental and adult-like features co-exist in the speech of typically-developing children and that developmental changes occur in connected speech behaviours between the ages of 2-3 years. In particular, a shift from equal numbers of close and open junctures, to a preference for close junctures is noted. Individual differences are also apparent between speakers, and these are discussed. PMID- 17852151 TI - Variability in cortical representations of speech sound perception. AB - Recent brain mapping studies have provided new insights into the cortical systems that mediate human speech perception. Electrocortical stimulation mapping (ESM) is a brain mapping method that is used clinically to localize cortical functions in neurosurgical patients. Recent ESM studies have yielded new insights into the cortical systems that mediate speech perception and how these systems vary as a function of individual differences. ESM methods are described and findings from recent ESM studies of speech perception are reviewed. The clinical implications of these findings are discussed as they relate to current understanding of how individual differences in listening abilities are reflected in the underlying cortical representations. PMID- 17852152 TI - Dislocations as a developmental marker in French language: a preliminary study. AB - In a previous study, Parisse suggested that subject dislocations in French language (e.g. "la fille elle dort") could be considered as a marker of morphosyntactic development in children with normal language development. The present study aimed to develop this proposition and to confirm it with experimental data, more specifically the fact that this development would go through a four-step process. Our prediction was that children would produce forms that correspond to successive steps in the developmental process (for example, forms [1] and [2], or [2] and [3]), but not forms that were very different (for example, forms [1] and [4], or [2] and [4]). In order to test this hypothesis, a sentence repetition task was administrated to 27 children aged 4 to 5. The results confirm the presence of a developmental trend in the use of dislocation in spontaneous language. At age 4, dislocations were frequent (30%), and tended to respect the gender (stage 3 and 4). At age 5, dislocations were rare (stage 4). Previous stages (1 and 2) would be observed in younger children. PMID- 17852153 TI - Fluency variation in adolescents. AB - The Speech Fluency Profile of fluent adolescent speakers of Brazilian Portuguese, were examined with respect to gender and neurolinguistic variations. Speech samples of 130 male and female adolescents, aged between 12;0 and 17;11 years were gathered. They were analysed according to type of speech disruption; speech rate; and frequency of speech disruptions. Statistical analysis did not find significant differences between genders for the variables studied. However, regarding the phases of adolescence (early: 12;0-14;11 years; late: 15;0-17;11 years), statistical differences were observed for all of the variables. As for neurolinguistic maturation, a decrease in the number of speech disruptions and an increase in speech rate occurred during the final phase of adolescence, indicating that the maturation of the motor and linguistic processes exerted an influence over the fluency profile of speech. PMID- 17852154 TI - Voicing status of word final plosives in Friedreich's Ataxia dysarthria. AB - In a previous study, the authors identified final plosive voicing contrast as the highest single error source in dysarthria associated with Friedreich's Ataxia in a group of Irish English-speaking participants. This study aimed to determine the acoustic features underlying misperceptions of voicing status and implications for clinical management. Words with final plosives were extracted from recordings of ten speakers with Friedreich's Ataxia. Various measures of the syllable rhyme were compared with intelligibility scores. Vowel duration, voicing in the closure, F1 frequency at mid-vowel and a drop in F1 at vowel termination accounted for 58% of the variance in the relevant intelligibility scores, with vowel duration being most heavily implicated. While inappropriate vowel duration is the factor most likely to lead to misperceptions of final plosive voicing status, other factors may overcome its effect. Therapeutic intervention with this population should be based on a comparison of intelligibility assessment with acoustic measurement. PMID- 17852155 TI - Refractory shock and asystole related to tramadol overdose. AB - INTRODUCTION: Tramadol use is largely considered safe. However, several lethal cases of tramadol intoxication were reported, suggesting an underestimated toxicity. We report for a tramadol overdose case in combination with other central nervous system depressants, leading to refractory shock requiring extracorporeal life support. CASE REPORT: A 33-year-old man was admitted in our intensive care unit for drug intoxication with coma, seizures, and hypotension without signs of heart failure. A few hours later, he developed a ventricular tachycardia, followed by a brief cardiac arrest in asystole with refractory shock requiring an extracorporeal life support, vasopressors, and hemofiltration. With this aggressive support, his overall status gradually improved. Repeated echocardiography showed an improvement in the cardiac function. The patient was weaned off extracorporeal life support on day eight and discharged on day 12. On admission, a urine analysis, using gas chromatography-mass spectrometry, showed high peaks of tramadol and desmethyltramadol with the presence of hydroxyzine, gabapentine, and clonazepam. The tramadol blood concentration measured by the high-performance liquid chromatography method-diode array detector was 23.9 mg/L, much higher than many previously reported fatal overdoses. No other drugs with potential cardiac toxicity, such as beta-blockers, calcium antagonists, antiarrythmic, antidepressants, meprobamate, or other xenobiotics were detected. CONCLUSION: This case illustrates that tramadol overdose may cause refractory shock and asystole when taken in combination with CNS depressants, and reminds all physicians to be vigilant with regard to the potential toxic effects of tramadol. PMID- 17852156 TI - Cessation of nail growth following Bajiaolian intoxication. AB - Bajiaolian (Dysosma pleianthum), a species in the Mayapple family (Podophyllum pelatum), has been widely used as a traditional Chinese herbal medication for the remedies of snake bite, tumor growth, post-partum recovery, and acne. It has also been used in western medicine, especially topically for various skin lesions. Both oral ingestion and dermal application may result in severe toxicity. The clinical presentations reported after Bajiaolian poisoning include nausea, vomiting, diarrhea, abdominal cramps, tachycardia, orthostatic hypotension, paralytic ileus, urinary retention, hepatorenal dysfunction, leukocytosis followed by leukopenia, thrombocytopenia, prolonged areflexia, prolonged paraethesia and sensory ataxia, dizziness, fever, memory impairment, hallucinations, paranoia, convulsion, fainting, and coma. There are no previous reports in the literature about the cessation of nail growth as a clinical presentation following Bajiaolian poisoning. We present a case of nail growth that was halted for more than seven years after a single case of Bajiaolian poisoning. PMID- 17852157 TI - Acute phenol poisoning: a life-threatening hazard of chronic pain relief. AB - BACKGROUND: Phenol (carbolic acid, a higher alcohol) has been used for local analgesic therapy for a long time. Several complications of phenol therapy can occur by exposure through inhalational, oral, and dermal routes. Renal and pulmonary toxicity arising from the exposure to injectable phenol, however, has only been reported in a few case reports. CASE PRESENTATION: A 50-year-old man inadvertently received 10 cc of 89% phenol injection. It resulted in the development of acute respiratory and renal failure requiring intubation and hemodialysis, respectively. He improved clinically with the recovery of renal function. However, the chest x-ray and CT scan showed persistent nodular pulmonary infiltrates which resolved by six months. CONCLUSION: We report here an unusual case of acute respiratory and acute renal failure following accidental overdose of phenol. The case highlights potential development of multiple organ failure with persistence of organ dysfunction, an unusual danger associated with the overdose of injectable phenol for neurolysis. PMID- 17852158 TI - Multivitamins and phospholipids complex protects the hepatic cells from androgenic-anabolic-steroids-induced toxicity. AB - INTRODUCTION: Androgenic-anabolic-steroids (AAS)-induced hepatotoxicity typically occurs with C-17 alkylated oral agents abused by exercising individuals at clinically recommended doses. Injectable compounds appear to have the same risk for hepatotoxicity, but are applied in doses three to six times higher than clinically recommended. AAS users occasionally try to avoid the well-known hepatotoxic effects associated with the abuse of a multitude of AAS agents, by using the pharmaceutical agent compound N a phospholipid/vitamin preparation. PRIMARY OBJECTIVE: The investigation of the actual hepatoprotective effect of compound N against AAS-induced toxicity. METHODOLOGY: This was an observational cohort study of 320 athletes; 160 were AAS users and the other 160 were not abusing any substances. Of the 160 users, 44 were using AAS and compound N (group A), and 116 were using solely AAS (group B). The 160 athletes abstaining from substances abuse acted as controls (group C). All athletes were tested for alterations in serum levels of hepatic enzymes. Enzyme levels before the study's onset and after the end of the 8-week AAS regimes were compared among the three groups, in order to delineate the hepatoprotective effect of compound N. RESULTS: Prior to our research all groups showed normal values in all enzymes except creatine kinase (CK). After the 8-week period, CK levels were slightly lower in group A, but without variation in Groups B and C; -Glutamyl Transferase (GT) levels remained normal. Groups A and C had no elevations in any of the enzymes, except CK, while in group B all enzymes' values were elevated above the normal range. The only factor differentiating AAS users in group A from those in group B was the use of compound N, thus the results being suggestive of the compound's detoxification effect. The severity of AAS abuse was positively associated with the degree of changes ( values) in all measured enzymes except GT and CK. CONCLUSIONS: Previous suggestions that serum hepatic enzyme elevations in exercising AAS abusers are connected to muscle fiber damage rather than the abuse itself, are contradicted by our results. Since all AAS abusing athletes were prone to exhibit elevations in enzymes' values, the mean values of group A were to be similar to those observed in group B, exceeding normal values. The group hepatic enzyme values of group B were significantly higher than the group C (control). Notably, group A did not have any statistically significant difference in the hepatic enzyme values compared to group C. The effect of exercise on these enzymes' elevations was ruled out by the comparability of training regimens and AAS toxicity was correlated to the severity of AAS abuse. PMID- 17852159 TI - Comment on "Ingestion of slow-release iron treated with gastric lavage - never say late". PMID- 17852160 TI - Osteonecrosis of the jaw and bisphosphonates: a comparison with white phosphorus, radium, and osteopetrosis. AB - INTRODUCTION: Recent reports of bisphosphonate-associated jaw osteonecrosis are reminiscent of earlier incidents in which a comparable syndrome was caused by occupational exposure to white phosphorus or radium. Osteonecrosis of the jaw is also caused by an inherited disease: osteopetrosis. This review analyzes the biomedical and social aspects of these four situations associated with jaw osteonecrosis. RESULTS: Clinical evidence is contradictory but suggests aminobisphosphonates cause rare cases of jaw necrosis. In addition to jaw problems, generalized skeletal defects characterize osteopetrosis and exposure to phosphorus or radium and there is evidence of decreased bone resorption in these conditions and with bisphosphonate therapy. CONCLUSION: Bisphosphonate-induced jaw necrosis appears to be an on-target toxicity as the same mechanism, inhibition bone resorption, probably underlies both the therapeutic and adverse effects. Since bisphosphonates are retained for long periods by bone the theoretical potential for skeletal toxicity is increased by using higher doses of potent aminobisphosphonates administered less frequently. PMID- 17852161 TI - Human methyl parathion poisoning. AB - BACKGROUND: Methyl parathion is classed as an extremely hazardous pesticide with a rodent LD50 of 6 to 24 mg/kg. It has been banned in numerous countries, but there are few reports of acute methyl parathion poisoning. METHODS: Plasma cholinesterase and acetylcholinesterase were measured in blood. Methyl parathion and the major metabolite 4-nitrophenol where measured in serum and urine. Based on the available concentration-time data, the pharmacokinetic parameters of methyl parathion were estimated for this patient. CASE REPORT AND RESULTS: A 29 year-old male ingested 50 to 100mL (12 to 24 g) of methyl parathion causing delayed and prolonged suppression of acetylcholinesterase but almost no clinical effects. Absorption was predicted to last for 30 hours and the bioavailability appeared to be very low. CONCLUSIONS: Although it is feasible the patient ingested much less, a tenth of his alleged ingestion dose is more than the oral LD50 in rats. Methyl parathion appears to be less toxic in humans than parathion for similar amounts ingested, which is not consistent with the two pesticides having similar rodent LD50. PMID- 17852162 TI - Hemodynamic effects of methadone and dihydrocodeine in overdose. AB - BACKGROUND: Opioid overdose is an increasing health problem worldwide. The cardiovascular toxicity of opioids contributes to morbidity and mortality in overdose but the hemodynamic effects of opioids reported in animal and human studies are contradictory. METHODS: We performed a prospective observational study of patients admitted to hospital following an overdose of methadone, dihydrocodeine, or low dose paracetamol (10 each). Basic cardiovascular indices including peripheral blood pressure, pulse rate, radial augmentation index and derived measures of aortic systolic, diastolic, pulse, and mean and end systolic pressures were measured every six hours for up to 18-23 hours after exposure or until hospital discharge. RESULTS: Dihydrocodeine and methadone significantly reduced peripheral and aortic systolic, mean and end systolic pressures. Both opioids significantly decreased peripheral pulse pressure, but only methadone decreased aortic blood pressure. Dihydrocodeine reduced systemic and aortic diastolic blood pressure, an effect not induced by methadone. Methadone significantly reduced peripheral pulse pressure. Augmentation index and heart rate, however, did not change. Both opioids decreased arterial oxygen saturation. CONCLUSION: These results suggest that dihydrocodeine and methadone in overdose both have a significant effect on central and peripheral hemodynamics. These effects might be expected to reduce cardiac afterload, providing a pharmacological explanation for the apparent benefit of opioids in cardiovascular diseases. PMID- 17852163 TI - Fatalities following skin exposure to arsenic. AB - Arsenic is a toxic metal that can cause death following exposure. In an unusual event, seven patients unintentionally applied a 30% arsenic solution to their entire body instead of a benzyl benzoate solution to treat their scabies. Hours later they developed severe skin reactions, including bullae, and were admitted to the hospital with gastrointestinal and cardiovascular disorders. Despite therapeutic interventions, three patients died and the rest were discharged from hospital with neurological sequelae. Toxicological analysis confirmed the presence of arsenic in the solution used by patients. PMID- 17852164 TI - Acute exenatide (Byetta) poisoning was not associated with significant hypoglycemia. PMID- 17852165 TI - Acute pulmonary edema associated with naphazoline ingestion. AB - In published reports of naphazoline ingestion, clinical effects are hypertension, bradycardia, pallor, diaphoresis, and respiratory distress. We report three cases of acute pulmonary edema after the intentional ingestion of naphazoline containing antiseptic first aid liquid. These cases presented with altered mental status, hypertension, bradycardia, and diaphoresis. Chest x-ray on admission revealed acute pulmonary edema. Two cases required mechanical ventilation. All of these clinical effects resolved within 24 hours and the patients were discharged with no sequelae. Since naphazoline stimulates the peripheral alpha-2 adrenergic receptor, we speculate that intense vasoconstriction may have elevated cardiac afterload and left atrial-ventricular blood volume and caused acute pulmonary edema. PMID- 17852166 TI - Illicit cathinone ("Hagigat") poisoning. AB - INTRODUCTION: Khat leaves (mainly cathinone and cathine) have been chewed for centuries as stimulants. Hagigat (capsules of 200 mg cathinone) have been marketed in Israel as a natural stimulant and aphrodisiac. The consequences of illicit exposure to cathinone are reported. METHODS: Prospective observational study of calls to the Poison Center regarding exposure to Hagigat during the course of 10 months. Demographic and clinical data were abstracted from patients' records and telephone follow up was performed. RESULTS: Data of 34 consecutive patients aged 16-54 years were analyzed. The amount consumed was (1/2)-6 capsules (ingestion-32, sniffing-2). Main clinical manifestations were headache, vomiting, hypertension, nausea, tachycardia, dyspnea, chest pain, and myalgia. Main complications were myocardial ischemia (3), pulmonary edema (2), and intracerebral hemorrhage (1), all in young subjects. Treatment was supportive; one patient underwent neurosurgery. CONCLUSION: Exposure to illicitly synthesized cathinone is associated with serious cardiovascular and neurological toxicity, even in young subjects. PMID- 17852167 TI - Dose-related illusions and hallucinations with zaleplon. PMID- 17852168 TI - All-E lutein and 3'-epilutein in the epidermis of chronic arsenic poisoning. AB - Identification and quantification of carotenoids in the epidermis of nine patients of chronic arsenic poisoning were done using isocratic reverse phase high performance liquid chromatography (HPLC). The major carotenoids in all the skin biopsies were all-E lutein and 3'-epilutein. Small amount of 2',3' anhydrolutein, all-E zeaxanthin, and 13-Z zeaxanthin were also present in some of the biopsy samples. Alpha-carotene, beta-carotene, and lycopene were not detected in any sample. The mean (+/- SD) concentration of all-E lutein in the epidermis of healthy volunteers was 1.09 +/- 0.26 microgram/g of wet tissue, whereas it was only 0.29 +/- 0.10 microgram/g in the diffuse dark brown spots of chronic arsenic poisoning. In raindrop-shaped discoloration spots of skin the mean concentration of all-E lutein was 0.86 +/- 0.29 microgram/g of wet tissue. The difference between the concentrations of all-E lutein in the epidermis of healthy volunteers versus patients was for the diffuse dark brown spots statistically significantly (p < 0.05) lower, while this was not significant for the raindrop-shaped discoloration spots. This study suggests that arsenic exposure reduces the number, as well as concentrations of, carotenoids in skin. PMID- 17852169 TI - Mass ethion poisoning with high mortality. AB - INTRODUCTION: Fifteen people who consumed a meal during a social ceremony at a remote farm developed symptoms and signs of organophosphate poisoning. METHODS: Information was gathered from villagers and doctors at the primary health center and district hospital. Serial measurements of plasma and red blood cell cholinesterase activity levels were carried out and the organophosphate compound was identified in blood samples. RESULTS: Clinical toxicity included abdominal pain, vomiting, diarrhea, excessive secretions, and respiratory distress. The victims were taken to a community health center about 30 km away where three people died. The others were taken to the district level hospital at Palanpur where five died. Of the seven remaining victims who were transferred to a tertiary care hospital at Ahmedabad, one died during transport and another succumbed within a few hours. The remaining five people were hospitalized. Three recovered within a week but two developed complications: one had a lung infection and the other had cerebral anoxia following cardiorespiratory arrest. The person with cerebral anoxia died after eight and a half months. Red blood cell cholinesterase levels on the day of admission correlated well with clinical severity and outcome of the patients. The pesticide was identified as ethion. CONCLUSIONS: Pesticide poisonings in developing countries have high morbidity and mortality rates, as facilities for immediate treatment are not readily available. Such incidents should sensitize clinical toxicologists, health authorities, and policy makers to the problems of pesticide poisoning in third world countries. PMID- 17852170 TI - Pediatric trichotillomania: descriptive psychopathology and an open trial of cognitive behavioral therapy. AB - In study 1, 46 children and adolescents with trichotillomania who sought treatment at 2 specialty outpatient clinics were assessed. Most children reported pulling hair from multiple sites on the body, presented with readily visible alopecia, reported spending 30-60 minutes per day pulling or thinking about pulling, and reported experiencing significant distress about their symptoms. Most were described by their parents as having significant problems in school functioning. Few children met criteria for obsessive-compulsive disorder or tic disorder. Child and family rates of other forms of psychopathology were high. In study 2, 22 of these children were enrolled in an open trial of individual cognitive behavioral therapy with particular attention to relapse prevention. Trichotillomania severity decreased significantly and 77% of children were classified as treatment responders at post-treatment and 64% at 6-month follow up. PMID- 17852171 TI - E-mailed standardized cognitive behavioural treatment of work-related stress: a randomized controlled trial. AB - The aim of this study was to assess the effects of a 7-week standardized cognitive behavioural treatment of work-related stress conducted via e-mail. A total of 342 people applied for treatment in reaction to a newspaper article. Initial screening reduced the sample to a heterogeneous (sub)clinical group of 239 participants. Participants were assigned randomly to a waiting list condition (n = 62), or to immediate treatment (n = 177). A follow-up was conducted 3 years after inception of the treatment. The outcome measures used were the Depression Anxiety Stress Scales (DASS-42) and the Emotional Exhaustion scale of the Maslach Burnout Inventory - General Survey (MBI-GS). Fifty participants (21%) dropped out. Both groups showed statistically significant improvements. Intention-to treat analysis of covariance (ANCOVAs) revealed that participants in the treatment condition improved significantly more than those in the waiting control condition (0.001

or = d > or = 0.5 (anxiety)). The between-group effects ranged from d = 0.6 (stress) to d = 0.1 (anxiety). At follow-up, the effects were more pronounced, but this result requires replication in view of high attrition at follow-up. The results warrant further research on Internet driven standardized cognitive behavioural therapy for work-related stress. Such research should include the direct comparison of this treatment with face-to-face treatment, and should address the optimal level of therapist contact in Internet driven treatment. PMID- 17852172 TI - Coding counsellor behaviour in motivational interviewing sessions: inter-rater reliability for the Swedish Motivational Interviewing Treatment Integrity Code (MITI). AB - The aim of this study was to evaluate inter-rater reliability when using the Swedish version of the Motivational Interviewing Treatment Code (MITI) as an adjunct to MI training, clinical practice and research. Coders were trained to use the MITI for scoring taped sessions. The 4-month basic training had a duration of 39 hours. Following training, 60 audio-taped live interviews were randomly assigned for MITI coding. Mean intra-class correlation (ICC) coefficients were calculated for 7 coders across all pairs of coders. Cronbach's alpha was calculated to estimate the covariance between each pair across their common interviews. Six months later, a second inter-rater reliability test was performed, when 5 coders coded the same 15 randomly selected tapes. At the second reliability testing the mean ICC was 0.81 and the mean Cronbach's alpha was 0.96. However, the ICC varied for different sub-variables of the MITI, ranging from 0.42 empathy to 0.79 for number of Closed questions. In conclusion, MITI shows promising potential to be a reliable tool to confirm and enhance MI training as well as practice in clinical settings and in evaluating MI integrity in clinical MI research. However, coder assessment of empathy and MI-spirit, "global" variables, requires further refinement. PMID- 17852173 TI - Post-traumatic growth and optimism as outcomes of an internet-based intervention for complicated grief. AB - This explorative study examines the effects of an internet-based cognitive behavioural therapy for complicated grief on post-traumatic growth and optimism. The study is part of a larger randomized controlled trial described in Wagner, Knaevelsrud, and Maercker (2006). The patients were randomly assigned to either a treatment group (n = 26) or a waiting list control condition (n = 25). The internet-based intervention consisted of exposure to bereavement cues, cognitive reappraisal exercises, and a module on integration and restoration. A short form of the Post-traumatic Growth Inventory (PTGI), the Life Orientation Test-Revised (LOT-R), and measures of complicated grief and psychopathological outcomes were administered. Results indicate that post-traumatic growth increased in the treatment group. No treatment effect was found for optimism. These findings contribute to the growing literature on personal growth in psychotherapy. PMID- 17852174 TI - Differentiating cognitive content between depressed and anxious outpatients. AB - Quantitative research suggests that depressed and anxious patients can be differentiated based on their cognitive content. This study used qualitative research methods to separate the specific components of open-ended depressive and anxious thought content in 79 psychiatric outpatients. Patients with major depressive disorder (MDD; n = 36), generalized anxiety disorder (GAD; n = 10), and other psychiatric disorders (PC; n = 33) were instructed to (a) describe their most bothersome problem; (b) imagine the worst possible negative outcome followed by the best possible positive outcome; and (c) describe associated thoughts and emotions for each scenario. The content of patients' responses were coded to examine (a) the types and severity of problems; (b) the presence or absence of hopelessness, catastrophizing, hopefulness, and unrealistic positive expectations; and (c) the presence or absence of particular emotions associated with imagined worst and best outcomes. More GAD patients than MDD and PC patients indicated anticipated anxious emotions associated with imagined worst outcomes, and fewer MDD patients than GAD and PC patients indicated anticipated happiness associated with imagined best outcomes. No group differences emerged for the other variables considered. These findings suggest that depressed and anxious patients differ in their cognitive expectancies about future life events in terms of their own anticipated emotional reactions. PMID- 17852175 TI - Engineered bone culture in a perfusion bioreactor: a 2D computational study of stationary mass and momentum transport. AB - Successful bone cell culture in large implants still is a challenge to biologists and requires a strict control of the physicochemical and mechanical environments. This study analyses from the transport phenomena viewpoint the limiting factors of a perfusion bioreactor for bone cell culture within fibrous and porous large implants (2.5 cm in length, a few cubic centimetres in volume, 250 microm in fibre diameter with approximately 60% porosity). A two-dimensional mathematical model, based upon stationary mass and momentum transport in these implants is proposed and numerically solved. Cell oxygen consumption, in accordance theoretically with the Michaelis-Menten law, generates non linearity in the boundary conditions of the convection diffusion equation. Numerical solutions are obtained with a commercial code (Femlab 3.1; Comsol AB, Stockholm, Sweden). Moreover, based on the simplification of transport equations, a simple formula is given for estimating the length of the oxygen penetration within the implant. Results show that within a few hours of culture process and for a perfusion velocity of the order of 10(-4) m s(-1), the local oxygen concentration is everywhere sufficiently high to ensure a suitable cell metabolism. But shear stresses induced by the fluid flow with such a perfusion velocity are found to be locally too large (higher than 10(-3) Pa). Suitable shear stresses are obtained by decreasing the velocity at the inlet to around 2 x 10(-5) m s(-1). But consequently hypoxic regions (low oxygen concentrations) appear at the downstream part of the implant. Thus, it is suggested here that in the determination of the perfusion flow rate within a large implant, a compromise between oxygen supply and shear stress effects must be found in order to obtain a successful cell culture. PMID- 17852176 TI - Confocal arthroscopy-based patient-specific constitutive models of cartilaginous tissues - II: prediction of reaction force history of meniscal cartilage specimens. AB - The theoretical framework developed in a companion paper (Part I) is used to derive estimates of mechanical response of two meniscal cartilage specimens. The previously developed framework consisted of a constitutive model capable of incorporating confocal image-derived tissue microstructural data. In the present paper (Part II) fibre and matrix constitutive parameters are first estimated from mechanical testing of a batch of specimens similar to, but independent from those under consideration. Image analysis techniques which allow estimation of tissue microstructural parameters form confocal images are presented. The constitutive model and image-derived structural parameters are then used to predict the reaction force history of the two meniscal specimens subjected to partially confined compression. The predictions are made on the basis of the specimens' individual structural condition as assessed by confocal microscopy and involve no tuning of material parameters. Although the model does not reproduce all features of the experimental curves, as an unfitted estimate of mechanical response the prediction is quite accurate. In light of the obtained results it is judged that more general non-invasive estimation of tissue mechanical properties is possible using the developed framework. PMID- 17852177 TI - Spinal stability and role of passive stiffness in dynamic squat and stoop lifts. AB - The spinal stability and passive-active load partitioning under dynamic squat and stoop lifts were investigated as the ligamentous stiffness in flexion was altered. Measured in vivo kinematics of subjects lifting 180 N at either squat or stoop technique was prescribed in a nonlinear transient finite element model of the spine. The Kinematics-driven approach was utilized for temporal estimation of muscle forces, internal spinal loads and system stability. The finite element model accounted for nonlinear properties of the ligamentous spine, wrapping of thoracic extensor muscles and trunk dynamic characteristics while subject to measured kinematics and gravity/external loads. Alterations in passive properties of spine substantially influenced muscle forces, spinal loads and system stability in both lifting techniques, though more so in stoop than in squat. The squat technique is advocated for resulting in smaller spinal loads. Stability of spine in the sagittal plane substantially improved with greater passive properties, trunk flexion and load. Simulation of global extensor muscles with curved rather than straight courses considerably diminished loads on spine and increased stability throughout the task. PMID- 17852178 TI - Human shoulder response to side impacts: a finite element study. AB - This study aimed at developing a shoulder finite element (FE) model able to simulate the dynamic behaviour and to predict injuries in case of side impacts. This model is an updated version of the initial Human Model for Safety (HUMOS) FE model of the human body. Simulations performed with the model have been compared to experimental results of side impact tests conducted previously at INRETS. The shoulder model response under lateral impact appears to be in good agreement with experimental data such as impact force and shoulder deflections for different impact speeds and impact directions. These results seem promising for future applications such as shoulder injury prediction in simulated car crashes. PMID- 17852179 TI - The influence of an elastic tendon on the force producing capabilities of a muscle during dynamic movements. AB - With increasing computer power, computer simulation of human movement has become a popular research tool. However, time to complete simulations can still be long even on powerful computers. One possibility for reducing simulation time, with models of musculo-skeletal system, is to simulate the muscle using a rigid tendon rather than the more realistic compliant tendon. This study examines the effect of tendon elasticity on muscle force output under different dynamic conditions. A single muscle, point mass model was used and simulations were performed varying the mass, the tendon length, the initial position, and the task. For simulations for relatively slow motion, as experienced for example in upper limb reaching motions or rising from a chair, tendon properties had little influence on muscle force, in contrast simulations of an explosive task similar to jumping or throwing tendon had a much larger effect. PMID- 17852180 TI - Modelling the effects of different fracture geometries and healing stages on ultrasound signal loss across a long bone fracture. AB - The effect on the signal amplitude of ultrasonic waves propagating along cortical bone plates was modelled using a 2D Finite Difference code. Different healing stages, represented by modified fracture geometries were introduced to the plate model. A simple transverse and oblique fracture filled with water was introduced to simulate the inflammatory stage. Subsequently, a symmetric external callus surrounding a transverse fracture was modelled to represent an advanced stage of healing. In comparison to the baseline (intact plate) data, a large net loss in signal amplitude was produced for the simple transverse and oblique cases. Changing the geometry to an external callus with different mechanical properties caused the net loss in signal amplitude to reduce significantly. This relative change in signal amplitude as the geometry and mechanical properties of the fracture site change could potentially be used to monitor the healing process. PMID- 17852181 TI - A fluid-immersed multi-body contact finite element formulation for median nerve stress in the carpal tunnel. AB - Carpal tunnel syndrome (CTS) is among the most important of the family of musculoskeletal disorders caused by chronic peripheral nerve compression. Despite the large body of research in many disciplinary areas aimed at reducing CTS incidence and/or severity, means for objective characterization of the biomechanical insult directly responsible for the disorder have received little attention. In this research, anatomical image-based human carpal tunnel finite element (FE) models were constructed to enable study of median nerve mechanical insult. The formulation included large-deformation multi-body contact between the nerve, the nine digital flexor tendons, and the carpal tunnel boundary. These contact engagements were addressed simultaneously with nerve and tendon fluid structural interaction (FSI) with the synovial fluid within the carpal tunnel. The effects of pertinent physical parameters on median nerve stress were explored. The results suggest that median nerve stresses due to direct structural contact are typically far higher than those from fluid pressure. PMID- 17852182 TI - A comparison of non-standard solvers for ODEs describing cellular reactions in the heart. AB - Mathematical models for the electrical activity in cardiac cells are normally formulated as systems of ordinary differential equations (ODEs). The equations are nonlinear and describe processes occurring on a wide range of time scales. Under normal accuracy requirements, this makes the systems stiff and therefore challenging to solve numerically. As standard implicit solvers are difficult to implement, explicit solvers such as the forward Euler method are commonly used, despite their poor efficiency. Non-standard formulations of the forward Euler method, derived from the analytical solution of linear ODEs, can give significantly improved performance while maintaining simplicity of implementation. In this paper we study the performance of three non-standard methods on two different cell models with comparable complexity but very different stiffness characteristics. PMID- 17852184 TI - The expression of TIMPs in cryo-preserved and freeze-dried amniotic membrane. AB - PURPOSE: To investigate the change of tissue inhibitor of metalloproteinase (TIMP) in cryopreserved amniotic membranes (AM) according to preservation time, and to evaluate the expression of TIMP in freeze-dried AM. METHODS: Cryopreserved or fresh AMs were incubated in dispase II for two hours at 37 degrees C and their epithelial cells were scraped with a cell scraper. Remaining stromal AM was minced and frozen in liquid nitrogen, and then treated with 0.1% diethyl pyrocarbonate. The mRNA levels of TIMP-1 and -2 were determined by reverse transcription-polymerase chain reaction (RT-PCR) in epithelial and stromal cells of fresh AM, AMs cryopreserved for 6 and 12 months, and freeze dried AM, respectively. Western blot analysis and immunohistochemical staining were performed to assess the expression of TIMP-1 in fresh, cryopreserved, and freeze dried AMs. RESULTS: RT-PCR revealed that mRNAs of TIMP-1 and -2 were expressed in the amniotic epithelial cells of both fresh and cryopreserved AMs, while the stromal cells of fresh or cryopreseved AMs and freeze-dried AM showed higher expression of TIMP-1 than TIMP-2 mRNA. On Western blot analysis, the level of TIMP-1 was more in fresh AMs than in cryopreserved or freeze-dried AM, but it was not statistically significant. CONCLUSION: TIMP-1 was expressed in cryopreserved AMs until 12 months, and the amount of expression was comparable to that in fresh AMs. PMID- 17852183 TI - Ocular surface expression and in vitro activity of antimicrobial peptides. AB - PURPOSE: Human ocular surface epithelia express four antimicrobial peptides (APs): beta -defensin (hBD) 1-3 and LL-37. Here the expression of additional APs (hBD 4-6, HE2beta 1; histatin-1, -3; liver expressed antimicrobial peptide-1, -2; macrophage inflammatory protein (MIP)-3alpha, and thymosin (T)beta -4) was sought and activity against common ocular pathogens studied. METHODS: AP expression was determined in human corneal and conjunctival epithelial cells (HCEC, HCjEC) by RT PCR and in corneal sections by immunostaining. Antimicrobial assays were performed to assess peptide (hBD 1-3, LL-37, MIP-3alpha, and Tbeta 4) activity against Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA), and Staphylococcus epidermidis (SE) in the presence of NaCl or tears. RESULTS: HCEC and HCjEC expressed MIP-3alpha and Tbeta 4. hBD 1-3, MIP-3alpha, and Tbeta 4 showed activity against PA. hBD-3 had potent activity against SA and SE, whereas hBD-2, MIP-3alpha and Tbeta 4 had moderate activity and hBD-1 had none. NaCl markedly attenuated, and tears almost completely inhibited the activity of hBD 1 2 and Tbeta 4, but not that of hBD-3. CONCLUSIONS: The ocular surface epithelia additionally express MIP-3alpha and Tbeta 4 which have moderate antimicrobial activity. The current data support a role for hBD-3 as an antimicrobial peptide in vivo, but call in to question the effectiveness of some other APs. However, further study is required to conclusively elucidate the physiological role of each AP. PMID- 17852185 TI - Necessary prone position time for human corneal endothelial precursor transplantation in a rabbit endothelial deficiency model. AB - PURPOSE: We previously performed human corneal endothelial precursor cell transplantation into the anterior chamber and maintenance of the prone position for 24 hours in a bullous keratopathy model. This time, we investigated the necessary postoperative time in the prone position for clinical application of precursor cell transplantation. METHODS: The sphere-forming assay was used to obtain precursors from cultured human corneal endothelial cells. Chloromethyl benzamidodialkylcarbocyanine (CM-DiI)-labeled precursor cells were injected into the anterior chamber of the eye in rabbits with corneal endothelial defects, and the prone position was maintained for 0, 1, 6, or 24 hours to allow attachment to Descemet's membrane. Rabbits maintained in the prone position for 24 hours without precursor cell transplantation were the controls. Each group was observed for 28 days after surgery, followed by histological examination and fluorescence microscopy. RESULTS: The mean corneal thickness of the rabbits kept in the prone position for 1, 6, or 24 hours after precursor cell transplantation was significantly less than that of the rabbits without adoption of the prone position after transplantation or the untransplanted rabbits at 14 days (p<0.005), 21 days (p<0.0001), and 28 days (p<0.0001) after surgery. And there was no significant differences in corneal thickness between the two groups kept in the prone position for 6 hours and 24 hours throughout the observation DiI positive human corneal endothelial-like hexagonal cells were detected on Descemet's membrane in the rabbits kept in the prone position for 1, 6, or 24 hours, but not in the control groups. Three of the six corneas in the 1-hour group showed focal edema and incomplete coverage of the endothelial defects. CONCLUSIONS: Our findings demonstrated that transplantation of human corneal endothelial precursors into the anterior chamber with adoption of the prone position for 6 hours treated bullous keratopathy in rabbits with similar efficacy to maintenance of the prone position for 24 hours after surgery. PMID- 17852186 TI - Effect of low fluence diode laser irradiation on the hydraulic conductivity of perfused trabecular meshwork endothelial cell monolayers. AB - OBJECTIVE: To determine the effect of low-fluence diode laser irradiation upon the fluid perfusion characteristics of cultured human trabecular meshwork cell monolayers when placed in a specially designed testing apparatus and subjected to fluid flow driven by a hydrostatic pressure gradient. METHODS: Two experimental series were conducted. In the first series, six low-fluence diode laser irradiation experiments were conducted using cultured human trabecular meshwork cell monolayers grown on filter supports. Upon reaching a steady state perfusion condition at approximately 5.0 mmHg, monolayers were irradiated at fluencies ranging from 0.2619 to 0.8571 J/cm2 using a diode laser (lambda=810 nm). Perfusion and data collection continued for 45 minutes post-irradiation, after which the monolayers were tested to determine post-experimental viability. Hydraulic conductivity values were analyzed for post-irradiation response in 2.5 minute intervals, grouped by viability. In the second series, a total of six irradiated experiments and six simultaneous nonirradiated control experiments were conducted. Fluence values of 0.3571 J/cm2 (n=3) and 0.4286 J/cm2 (n=3) were used. Hydraulic conductivity values were analyzed for post-irradiation response in 2.5-minute intervals, grouped by irradiated vs. nonirradiated control groups. RESULTS: In the first series, analysis showed that the viable monolayers exhibited a statistically significant increase in hydraulic conductivity (p<0.001) from 10 minutes post-irradiation onward. The non-viable monolayers exhibited a statistically significant decrease in hydraulic conductivity. In the second series, irradiated groups showed a significant difference (p<0.001) from nonirradiated controls from 10 minutes post-irradiation onward. CONCLUSION: Low fluence diode laser irradiation increases hydraulic conductivity in viable perfused TM cell monolayers when compared to baseline values or simultaneous nonirradiated controls while decreasing hydraulic conductivity in nonviable monolayers. PMID- 17852187 TI - Methotrexate delivery to the eye using transscleral hydrogel iontophoresis. AB - PURPOSE: To evaluate methotrexate penetration and distribution profile in ocular structures after short low current transscleral hydrogel iontophoresis. METHODS: Methotrexate iontophoresis was studied in rabbits using drug-loaded hydrogels mounted on a portable iontophoretic device. Drug distribution profile was evaluated 2, 4, and 8 hours after iontophoretic treatment of 1.6 mA/cm2 for 4 min. Ocular drug levels were also determined two hours after iontophoretic treatment of 5 mA/cm2, compared to mock iontophoresis and intravitreal injection of methotrexate. RESULTS: Therapeutic drug levels were maintained for at least 8 h at the sclera and retina and for 2 h at the aqueous humor following the iontophoretic treatment. After increasing the current density, a twice-higher concentration was achieved at the vitreous and 8 to 20 time higher concentrations at the retina and sclera. CONCLUSIONS: A short low current non-invasive iontophoretic treatment using methotrexate-loaded hydrogels has a potential clinical value in treating ocular inflammatory diseases and intraocular lymphoma. PMID- 17852188 TI - The experimental research of rabbit's sclerotomy sites undergoing transconjunctival sutureless vitrectomy. AB - AIMS: To investigate the healing mechanism of the rabbit's sclerotomy sites undergoing the Transconjunctival Sutureless Vitrectomy (TSV). METHODS: Thirty-two rabbits (Thirty-two eyes) were divided into four groups: The rabbits performed with the core vitrectomy and air tamponade were Group A, performed with the core vitrectomy as Group B, performed with the non-core vitrectomy and air tamponade as Group C, and the non-core vitrectomy as Group D. The sclerotomy sites were observed by the Ultrasound Biomicroscope (UBM model 840, Humphrey Instruments, San Leandro, CA, USA) on days 1, 3, 5, and 9 postoperatively, and the diameter of the internal and the external aperture was estimated on postoperative day 1. The pathological study of the sclerotomy sites on days 3, 5, and 9 postoperatively were investigated under the light microscope. RESULTS: The Ultrasound Biomicroscope and the pathological sections showed that the healing course of the sclerotomy sites lasted nine days. On postoperative day 1, the vitreous incarceration (19/32, 59.4%), the fluid cavity (18/32, 56.3%), and the air cavity under the conjunctiva (7/16, 43.8%) existed in some cases. The diameter of the internal aperture in Group A and Group B was less than Group C and Group D on day 1 postoperatively, P<0.001. The diameter of the external aperture did not show significant difference in any of the groups. The pathological study verified the healing course was the granulation reaction. CONCLUSION: The healing mechanism of the rabbit's sclerotomy sites undergoing the (TSV) is the granulation reaction accompanied with the elastic recovery of the sclera. PMID- 17852189 TI - Toxoplasma gondii detection by nested polymerase chain reaction in lens aspirate and peripheral blood leukocyte in congenital cataract patients: the first report from a tertiary eye hospital in India. AB - PURPOSE: To detect T. gondii DNA and specific antibodies in lens aspirates (LA) and peripheral blood leucocytes (PBL) of congenital cataract patients. METHODS: ELISA for T. gondii antibodies on sera nPCR for T. gondii DNA (B1 gene) on LA and PBL were performed for 52 patients. RESULTS: T. gondii DNA was detected in 29 (55.8%) of the 52 patients (LA-14, PBL-13, LA and PBL-2, and specific IgM in 2 sera). nPCR in PBL was more sensitive than ELISA (p<0.005). CONCLUSION: nPCR is a sensitive technique to detect T. gondii from LA and PBL in congenital cataract patients. PMID- 17852190 TI - Comparison of 2-methoxyestradiol and methotrexate effects on non-Hodgkin's B-cell lymphoma. AB - PURPOSE: Methotrexate (MTX) is the most commonly used chemotherapeutic agent to treat primary central nervous system lymphoma (PCNSL) and intraocular lymphoma (IOL). 2-methoxyestradiol (2ME2) is a potent antitumor and anti-angiogenesis agent which, unlike other cytotoxic drugs, has minimal toxicity. In this study, anti-proliferative, apoptotic, and cell-cycle effects of 2ME2 and MTX were compared to evaluate 2ME2 efficacy in human lymphoma cells, models for non Hodgkin B cell lymphomas. METHODS: The cells were cultured and incubated with varying concentrations of 2ME2 or MTX. A tetrazolium-based colorimetric assay was used to quantify the anti-proliferative effects of 2ME2 and MTX using a microplate reader. To detect apoptotic and cell cycle distribution changes induced by 2ME2 and MTX, the cells were stained with Annexin V-FITC and/or propidium iodide (PI) and analyzed by flow cytometry. RESULTS: Lymphoma cell proliferation was inhibited by 50% at concentrations ranging from 0.4 to 1 microM for 2ME2 and 0.06 to 0.2 microM for MTX. Induction of apoptosis by 2ME2 and MTX was observed in the tested cells. 2ME2 was a G2/M-phase specific blocker whereas MTX was an S-phase specific blocker in cell cycle analyses. At 1 microM concentration, 2ME2 and MTX showed similar anti-proliferative effect on the lymphoma cell lines. In previously reported studies, for normal endothelial cells, 1 microM 2ME2 showed no appreciable toxicity, while MTX at this same concentration exhibited significant cytotoxicity. 2ME2 at a therapeutic target concentration of 1 mu M may be an effective and relatively non-toxic drug for the treatment of PCNSL with IOL. CONCLUSIONS: Our study of the effect of 2ME2 and MTX on anti-proliferation, apoptosis, and cell cycling suggests that 2ME2 is a potential agent for treating PCNSL and IOL. PMID- 17852191 TI - Serum cytokine levels in active uveitis and remission. AB - Serum levels of interleukin(IL)-8, IL-6, and (TNF)-alpha were measured in 25 patients during active uveitis and uveitis in remission and compared to age matched controls. Levels of IL-8 and IL-6 were significantly elevated in patients with active disease and were decreased during remission. IL-8 levels were highest in patients with anterior uveitis, with greatest difference between active disease and remission. No consistent pattern was observed for TNF-alpha. In conclusion, serum cytokine levels are elevated in active noninfectious uveitis. The rise in IL-8 may suggest innate immune mechanisms in the acute disease, while IL-6 participates in modulation of inflammation in the chronic disease. PMID- 17852192 TI - Increase in Fe3+/Fe2+ ratio and iron-induced oxidative stress in Eales disease and presence of ferrous iron in circulating transferrin. AB - Eales disease was shown to be associated with oxidant stress and weak antioxidant defense. Total iron, ferrous iron, thiobarbituric acid reactive substances (TBARS), and ceruloplasmin were estimated in the blood samples of patients with inflammation, perivasculitis, and venous insufficiency. Levels of ferric iron were determined from the difference in those of total iron and ferrous iron. All biochemical parameters were estimated in age and sex-matched controls. Fe3+/Fe2+ ratio was greater in patients with Eales disease than in normal controls. Similar increase in TBARS and ceruloplasmin levels were noted. The patients were treated with prednisone and vitamins E and C, then Fe3+/Fe2+ ratios and TBARS decreased progressively; the active state of the disease was reduced to 16%. So Fe3+/Fe2+ ratio in addition to TBARS levels could be considered an index of the active state of the disease. Circulating transferrin in blood did contain ferrous iron. Binding of ferrous iron to transferrin was confirmed by estimating iron-binding capacity using ferrous ammonium sulphate. PMID- 17852193 TI - Identification of novel mutations in the XLRS1 gene in Chinese patients with X linked juvenile retinoschisis. AB - X-linked juvenile retinoschisis (XLRS) is a major cause of macular degeneration in young men. In this study we analyzed all six exons of the XLRS1 gene in four sporadic XLRS patients and in an affected family in China who were recently diagnosed. We found there are five different mutations with four containing missense point mutations and one having a frame-shift deletion. Among these mutations both c.644A>T and c.520delC are novel and have not been previously reported. Moreover all the second-generation offsprings and most of the third generation ones in the affected family were found to carry the mutations bearing X chromosome. The discovery of novel mutations in the XLRS1 gene would increase the available information about the spectrum of genetic abnormalities causing XLRS. Although the limited data failed to reveal a correlation between mutations and disease phenotypes our identification of novel mutations in the XLRS1 gene will facilitate early and correct diagnosis and genetic counseling regarding the prognosis of XLRS disease. PMID- 17852194 TI - The role of clusterin in in vitro ischemia of human retinal endothelial cells. AB - Clusterin has been reported to be up-regulated in diverse pathophysiological stresses, but its role is controversial. In this study, we investigated the role of clusterin under in vitro ischemia of human retinal endothelial cells (HRECs). When HRECs were exposed to oxygen-glucose deprivation (OGD), clusterin expression increased, whereas von Willebrand factor (vWF), occludin, and zonula occludens (ZO-1) markedly decreased. Interestingly, loss of tight junction proteins and death of HRECs in OGD conditions were restored by clusterin treatment. Our results suggest that the enhanced clusterin in OGD conditions may play a protective role against ischemia-induced tight junction protein loss and HRECs death. PMID- 17852195 TI - Effect of carbogen (95% O2/5% CO2) on retinal oxygenation in dark-adapted anesthetized cats. AB - This work assessed the relative effects of inspiring carbogen (95% O(2)/5% CO2) and 100% O2 on intraretinal PO2 and oxygen consumption in the cat retina. Oxygen microelectrodes were used to measure the distribution of oxygen in the central retina of dark-adapted anesthetized cats during normoxia, 100% O2 breathing, and carbogen breathing. Profiles of oxygen tension (PO2) as a function of retinal depth were recorded. Changes in PO2 caused by the transient administration of carbogen and 100% oxygen were also measured at selected retinal depths. Average PO2 values at the choroid, at the boundary between the inner and outer retina, and across the inner retina were significantly higher during inspiration of carbogen than 100% O2. There were no significant differences among conditions in outer retinal oxygen consumption. During the transient gas administration, average changes in PO2 generally increased with depth. At the end of gas administration, the decay of PO2 within the retina occurred quickly, meaning that short-term gas administration may have little therapeutic value. PMID- 17852196 TI - Screening of genes associated with termination of the critical period of visual cortex plasticity in rats. AB - PURPOSE: To investigate the molecular mechanism involved in the termination of the critical period of visual cortex plasticity in the rat. METHODS: The rats were divided into two groups, one group was dark-reared for 67 days after birth, while the other group was dark-reared for 60 days and then put under a normal light/dark cycle for 7 days. A subtracted cDNA library was constructed from the visual cortex, and differentially expressed genes were screened by nested PCR, reverse Northern hybridization, sequencing, and homology analysis. RESULTS: Fourteen genes were found to be up-regulated in the visual cortex. These included 13 known genes and a novel fragment (Genbank submission EB174193). Of the known genes, three genes encoding beta -tubulin, myelin basic protein, and cyclophilin were previously reported to be associated with visual cortex plasticity. CONCLUSION: A set of candidate genes related to the termination of the critical period was identified using the subtracted cDNA library. This work provides an important basis for understanding the molecular mechanisms involved in the termination of plasticity in the visual cortex. PMID- 17852197 TI - Neural correlate of vernier acuity tasks assessed by functional MRI (FMRI). AB - Vernier acuity refers to the ability to discern a small offset within a line. However, while Vernier acuity has been extensively studied psychophysically, its neural correlates are uncertain. Based upon previous psychophysical and electrophysiologic data, we hypothesized that extrastriate areas of the brain would be involved in Vernier acuity tasks, so we designed event-related functional MRI (fMRI) paradigms to identify cortical regions of the brain involved in this behavior. Normal subjects identified suprathreshold and subthreshold Vernier offsets. The results suggest a cortical network including frontal, parietal, occipital, and cerebellar regions subserves the observation, processing, interpretation, and acknowledgment of briefly presented Vernier offsets. PMID- 17852200 TI - Repression of transfusion-related acute lung injury: role of anti-cytokine and anti-chemokine Ab. PMID- 17852199 TI - Co-transfection of GK and mhPINS genes into HepG2 cells confers glucose stimulated insulin secretion. AB - BACKGROUND: The purpose of this study was to construct an 'artificial beta cell' that can exhibit physiologic glucose-stimulated insulin secretion for the treatment of type 1 diabetes. METHODS: Retroviral vector containing the glucokinase (GK) gene and mutated human proinsulin (mhPINS) gene was constructed. HepG2 cells were first infected with recombinant retrovirus carrying the GK and mhPINS genes, then selectively cultured with G418 to obtain the positive clones. GK and mhPINS gene transcription and expression were identified by radioimmunity, Western blot and RT-PCR techniques. Finally, the dose-response effect of glucose on insulin secretion from those HepG2 cells that expressed both GK and mhPINS genes was tested with HepG2 cells that only expressed the mhPINS gene as a control. RESULTS: HepG2 cells with transferred GK and mhPINS genes were selectively cultured with G418 and the positive clones were obtained in 3 weeks. Four clones with GK and mhPINS gene expression were selected from 20 positive clones by radioimmunity and Western blot. We picked up one clone with a strong GK and mhPINS gene expression and named it clone Beta. In clone Beta, differences in insulin secretion at 0.5 and 0.75 mmol/L glucose concentrations were not significant (P>0.05) and differences in insulin secretion at 2.0, 3.0, 4.0, 5.0 and 6.0 mmol/L glucose concentrations were not significant (P>0.05), while there were significant differences in insulin secretion at other glucose concentrations(P<0.05). The artificial beta cell, clone Beta, obtained a glucose stimulated insulin secretion with maximal insulin secretion at 1.75-2.00 mmol/L glucose concentrations. DISCUSSION: An artificial beta cell that exhibits glucose stimulated insulin secretion can be constructed successfully. PMID- 17852201 TI - UC blood infection with clinical strains of Mycobacterium tuberculosis: a novel model. AB - BACKGROUND: Use of unrelated cord blood transplantation (UCBT) is increasing, yet high rates of mortality secondary to infection remain a problem. We investigated the utility of using umbilical cord blood (UCB) as a model to study a naive cell population challenged by Mycobacterium tuberculosis. METHODS: Mononuclear cells were isolated from nine UCB samples and infected with each of four distinct strains of M. tuberculosis. The isolates used were two highly transmissible clinical strains, the virulent laboratory strain H37Rv and a unique strain isolated from only one case (i.e. non-virulent). CFU were assessed at 3 h post infection (day 0) and at day 7 to generate growth curves. Viability of the mononuclear cells was assessed prior to infection, 3 h post-infection and at days 3, 5 and 7 post-infection. IFN-gamma and TNF-alpha levels were determined at 24 h post-infection. RESULTS: All three of the virulent strains demonstrated rapid growth in UCB cells that was significantly faster than the growth rate observed for the non-virulent unique isolate. There was no significant decrease in UCB cell viability after the 7-day incubation period regardless of infecting isolate. UCB cells secreted IFN-gamma in response to infection, with no significant difference related to infection with different isolates. However, there was a significant increase in the amount of TNF-alpha elicited following infection with the non-virulent isolate compared with the virulent isolates. DISCUSSION: These results show that UCB can be used as a model to study infection, hopefully leading to new therapies for neonates and UCBT recipients. PMID- 17852202 TI - Localized and generalized disorders of the locomotor system--psychosocial and gender aspects: a ten year follow-up of rehabilitation. AB - PURPOSE: To evaluate localized disorders (LD) and generalized disorders (GD) of the locomotor system to differences in gender, personal and psychosocial factors in relation to outcome 10 years after the rehabilitation was initiated. METHOD: A total of 372 individuals (174 men and 198 women) representing two diagnostic groups, localized disorder (LD) and generalized disorder (GD) of the locomotor system, were followed for 10 years with regard to sick benefit (SB) and disability pension (DP) in relation to psychosocial background, Sense of Coherence (SOC) and Perceived Health (PH). RESULTS: Men with GD were more often single and had a lower SOC. Women with GD had more psychosocial markers and worse PH. Women with GD were more often on sick leave three years after rehabilitation and more often claim SB as well as DP after 10 years. Men with a low SOC and women with only compulsory school education had an increased risk of having a GD. CONCLUSION: The presence of GD of the locomotor system could be a reminder of the advisability to explore the patient's psychosocial condition in order to improve medical as well as vocational rehabilitation. PMID- 17852203 TI - The demand for rehabilitation therapists in Beijing health organizations over the next five years. AB - PURPOSE: To estimate the demand for rehabilitation therapists in Beijing health organizations over the next 5 years. METHODS: A literature search was carried out to confirm the distribution of rehabilitation therapists in Beijing health organizations in the past and to predict the demand for rehabilitation therapists in Beijing hospitals over the next 5 years by linear regression and logistic curve fitting. RESULTS: The total demand for rehabilitation therapists in Beijing in 2007 and 2010 will be 1480-1620 and 2240-2530, respectively. CONCLUSIONS: The allocation and training of manpower specialized in rehabilitation therapeutics for the rehabilitation departments of polyclinics in Beijing should be improved. PMID- 17852204 TI - Clinical prognostic factors for bladder function recovery of patients with spinal cord and cauda equina lesions. AB - OBJECTIVE: To investigate the relationship between lesion severity and other clinical factors and bladder function recovery. PATIENTS AND METHODS: The charts of 269 patients with traumatic and non traumatic spinal cord lesion (SCL) were reviewed and the following information was recorded: lesion to admission time, injury variables, length of stay and neurological status. At five months, urological outcome was assessed by voiding modalities, and urodynamics according to International Continence Society. Logistic approach with univariate and multivariate analysis. RESULTS: Both ASIA impairment at admission and age were significantly correlated with bladder function outcome. None of the patients with ASIA A impairment at admission reached volitional voiding at five months. ASIA B patients had a 90% lower probability of achieving good bladder control and ASIA C ones a 65% lower than ASIA D patients (p < 0.05). Older patients had a significant lower probability (60%) of achieving volitional voiding than younger ones (p < 0.05). Of the 121 patients with ASIA D impairment at discharge only 78 voided spontaneously and showed a higher frequency of cervical lesions and a lower frequency of detrusor-external sphincter dyssynergia. DISCUSSION AND CONCLUSION: Bladder recovery in patients with complete SCL is limited. ASIA B patients showed a better neurological recovery and, concurrently, better bladder function recovery than ASIA A patients, thus demonstrating the importance of sensation preservation for recovery. Younger patients show better bladder recovery than older ones, probably because of different efficiency of spinal cord plasticity. Finally, patients with good neurological recovery may not achieve volitional voiding. Patients with bladder function recovery show a higher frequency of central cord and Brown-Sequard syndromes (with better prognosis) and a lower frequency of detrusor-sphincter dyssynergia. PMID- 17852205 TI - Factors associated with life satisfaction in Japanese stroke outpatients. AB - PURPOSE: To measure life satisfaction in Japanese stroke outpatients and randomly sampled community residents and to investigate variables influencing their life satisfaction. METHOD: Data on the demographic and clinical profiles, Satisfaction in Daily Life (SDL), other measurements, were obtained from 869 stroke outpatients (552 males, 317 females) and 748 community-dwelling elderly (360 males, 388 females), aged 55 years and older. Differences in categorical variables and continuous variables were tested by chi-square test and ANCOVA with age as the covariate, respectively. RESULTS: The 11 SDL items were subjected to a factor analysis, which extracted two factors. Factor 1 (F1), labeled as 'satisfaction with one's own abilities', included satisfaction with housework, self-care, gait, physical health, hobby and leisure, social intercourse and mental health. Factor 2 (F2), 'satisfaction with external factors', included satisfaction with partner/ family relationship, economic state and social security, and house facilities. Both F1 and F2 scores were significantly lower for stroke outpatients (M = 19.7 and 10.9, respectively) than for community dwelling elderly (M = 28.2 and 12.0, respectively) (p < 0.001). Living conditions were significantly associated with F2, but not with F1. Males living alone scored lowest on F2 than the others for both groups. Among stroke outpatients, both F1 and F2 scores differed significantly by the type of hemiparesis and the severity of aphasia. CONCLUSIONS: SDL of stroke outpatients, which was lower than community-dwelling elderly, differed by the type of hemiparesis, the severity of aphasia, and living conditions. The effects of living conditions might vary with gender. PMID- 17852206 TI - Gender differences in amputation outcome. AB - PURPOSE: To assess the influence of gender on the success of limb-fitting after amputation. METHODS: One-hundred and five successive in-patients admitted to an amputee rehabilitation ward were followed to assess the success of limb-fitting at discharge. The influence of demographic, clinical and social factors on the success of lower limb-fitting was assessed using linear regression analysis and group comparisons. RESULTS: There were 35 (33%) women in a cohort of 105 successive admissions. Men and women were comparable in terms of age, length of stay, medical comorbidity and level of amputation. Women were less likely to be successfully fitted with a prosthetic limb at discharge than men (42.9% vs. 68.6%, p = 0.011), and more women lived alone (57.1% vs. 38.6%, p = 0.021). Linear regression revealed that gender was an independent significant factor in the success of limb-fitting; age, level and cause of amputation, co-morbidity and length of stay were not significant factors. CONCLUSIONS: Women were less likely to be successfully fitted with a lower limb prosthesis after amputation. PMID- 17852207 TI - Cognitive representations of disability behaviours in people with mobility limitations: consistency with theoretical constructs. AB - PURPOSE: Disability is conceptualized as behaviour by psychological theory and as a result of bodily impairment by medical models. However, how people with disabilities conceptualize those disabilities is unclear. The purpose of this study was to examine disability representations in people with mobility disabilities. METHOD: Thirteen people with mobility disabilities completed personal repertory grids (using the method of triads) applied to activities used to measure disabilities. Ten judges with expertise in health psychology then examined the correspondence between the elicited disability constructs and psychological and medical models of disability. RESULTS: Participants with mobility disabilities generated 73 personal constructs of disability. These constructs were judged consistent with the content of two psychological models, namely the theory of planned behaviour and social cognitive theory and with the main medical model of disability, the International Classification of Functioning Disability and Health. CONCLUSIONS: Individuals with activity limitations conceptualize activities in a manner that is compatible with both psychological and medical models. This ensures adequate communication in contexts where the medical model is relevant, e.g., clinical contexts, as well as in everyday conversation about activities and behaviours. Finally, integrated models of disability may be of value for theory driven interdisciplinary approaches to disability and rehabilitation. PMID- 17852208 TI - Clinical significance of specific spinal mobilization for patients with ankylosing spondylitis evaluated by quantitative assessments and patient interviews. AB - PURPOSE: To assess individual responses to specific spinal mobilization (SSM) in terms of spinal mobility, perceived stiffness, pain and activities of daily living (ADL) in patients with Ankylosis Spondylitis (AS), and whether and how interviews supported or supplemented the quantitative results. METHODS: Spinal mobility was recorded by the fingertip-to-floor distance, the Modified Schober Test, myerinometer, and the chest expansion test. The measures corresponding to sites targeted by SSM was used as effect variables, and the other as control variables. Visual analogue scales assessed pain and stiffness. The Bath Ankylosing Spondylitis Functional Index assessed ADL. A single subject experimental design was applied. The patients' experiences were investigated by semistructured qualitative interviews. RESULTS: Six patients completed 12 sessions of SSM. In five patients spinal mobility improved by 6-38%, and perceived stiffness reduced by 6-82%. Further improvements were found after three months. Improvements were not seen in the control variables. The interviews revealed that to become less stiff had various meanings for the patients, the SSM helped to get control of motion, and the conversations with the therapists enabled them to cope with the situation. CONCLUSIONS: The findings suggest that SSM can diminish spinal stiffness, but this had different meanings for the patients. What were important were what they experienced and learnt during the therapy process. PMID- 17852209 TI - Perceptual-motor coordination in persons with mild intellectual disability. AB - BACKGROUND: There is limited experimental evidence to support the view that individuals with intellectual disabilities (ID) have a deficit in motor control. This work is a first attempt to evaluate their motor coordination. PURPOSE: The study assessed the relationship between cognitive ability and sensorimotor integration. The clinical hypothesis is that adults with ID fall below non-ID adults in motor skills that involve hand-eye coordination. METHOD: A group of 42 adults with ID (ID group) was compared to 48 age-matched typical adults (TA) using a mixed experimental design ('Task' as the within-subjects factor and 'Group' as the between-subjects factor). Participants performed the following tests twice: Box-and-Blocks, 25-Grooved-Pegboard, Stick Catching and overhead Beanbag-Throw. Pearson correlations and ANOVAs were used to test the hypothesis (p < or = 0.05). RESULTS: As expected, TA outperformed the ID group in all tests regardless of the hand used during for the assessment. However, TA individuals scored significantly better with one hand (i.e., the preferred and dominant hand) as opposed to persons with ID, who exhibited no hand preference. Test-retest correlations among the first and second assessment scores yielded moderate-strong coefficients, depending on the type of test (Box-and-Blocks = 0.92 and 0.96, 25 Grooved-Pegboard = 0.69 and 0.83, Stick-Catching = 0.88 and 0.94, Beanbag-Throw = 0.58 and 0.91 for ID and TA, respectively). DISCUSSION: Difficulties in the integration of perceptual information into motor action may result in inadequate solutions to daily motor problems. As it stems from our results, intellectual disability relates to inability to integrate visual inputs and hand movements. In people with mild ID such inability is observed using both hands (i.e., they show no hand preferences). Poor perceptual-motor coordination might have a functional significance in that it may lead to exclusion from vocational and recreational activities, and a decreasing competence of ADL. Assessing coordination in adults with ID may contribute to understanding the nature of the ID condition and may encourage an early rehabilitation. PMID- 17852210 TI - Functional activities of the upper extremity of young adults with cerebral palsy: a limiting factor for participation? AB - PURPOSE: To assess functional activities of the upper extremity of young adults with cerebral palsy (CP) and to determine their relations with participant characteristics and participation. METHOD: Assessment of functional activities of the upper extremity was performed on 103 participants (aged 16-20 years) with the Melbourne assessment and the Abilhand Questionnaire. Participation was measured with the Life Habits Questionnaire. Participant characteristics included age, gender, limb distribution of the spastic paresis, educational level and gross and fine motor function. Relations among these variables were studied by means of correlation coefficients and linear regression analysis. RESULTS: Limitations in functional activities of the upper extremity were related to the limb distribution of the spastic paresis and were especially present in quadriplegic participants. Significant correlations between participant characteristics and measures of functional activities were present. Limitations in functional activities of the upper extremity, measured with the Abilhand Questionnaire, were an important determinant for participation, in addition to the gross motor function and educational level. CONCLUSION: Limitations in functional activities of the upper extremity are an important determinant for restrictions in participation in young adults with CP. It is recommended to include assessment of functional activities of the upper extremity in patients with CP. PMID- 17852212 TI - The experience of men using an upper limb prosthesis following amputation: positive coping and minimizing feeling different. AB - PURPOSE: Psychosocial factors are likely to play a crucial role in adjustment to upper limb amputation and prosthesis use, and yet have received only minimal exploration within the literature. This study therefore, sought to gain a rich understanding of the experience of living with an upper limb amputation and of using a prosthetic arm and hand. METHODS: The qualitative method of Interpretive Phenomenological Analysis was used. Purposive sampling culminated in a homogenous sample of 11 males with unilateral upper limb amputations, who wore a prosthesis at least weekly. Semi-structured interviews were carried out, transcribed and analysed according to the methodology. RESULTS: Participants identified a theme of ongoing awareness of difference in appearance and ability. Consequently, participants described themes of psychosocial and functional adjustment to minimize this sense of difference. This was facilitated by the participants' prostheses and their positive coping style. Within this, participants also identified the personal meanings of their prosthesis and highlighted the terms of its use. The minimization of their sense of difference resulted in participants regaining a sense of worth. CONCLUSIONS: The findings offer a greater psychological insight into adjustment from an upper limb amputation and the role of prostheses. These findings have implications for both the clinical rehabilitation of patients who undergo upper limb amputations, as well as for future research into the use and value of prostheses in facilitating the adjustment to this experience. PMID- 17852211 TI - Measuring participation in people living with multiple sclerosis: a comparison of self-reported frequency, importance and self-efficacy. AB - PURPOSE: To compare three dimensions related to participation in everyday situations in community-dwelling adults with multiple sclerosis (MS). METHODS: Mail survey was obtained from 112 respondents. Data were analyzed using Kendall's tau-b correlation coefficients between responses to participation items relative to three question dimensions (importance, frequency, and self-efficacy) and criterion variables (mobility, depression, general health, fatigue and pain). RESULTS: No significant associations were found between item responses in the importance dimension and the criterion variables. Weak associations were found for items in the frequency dimension, and stronger associations were found for items in the self-efficacy dimension. CONCLUSIONS: Different dimensions of participation in specific life situations yielded different responses and associations of those responses with key criterion measures. Subjective importance of participating in everyday situations is relatively independent of measures of mobility, general health, depression, fatigue and pain. Subjective judgments of self-efficacy for participation are more closely linked to these criterion measures. Caution is warranted when interpreting scales of participation because participation is a complex construct, potentially composed of several dimensions. PMID- 17852213 TI - A longitudinal comparison of consumer-directed and agency-directed personal assistance service programmes among persons with physical disabilities. AB - PURPOSE: To compare outcomes for persons who were enrolled in an agency-directed personal assistance services (PAS) programme and then changed to a consumer directed PAS programme. METHOD: A convenience sample was used for this longitudinal study. In-home interviews were conducted by a trained data collector from April 2000 to December 2001. RESULTS: Participants reported more satisfaction and safety with personal assistance, and fewer unmet needs after receiving consumer-directed services than after receiving agency-directed services. Other variables related to outcomes included race and ethnicity, employment, functional status, unmet needs, and the level of confidence in obtaining help if assistance is unavailable. Participants (74%) also reported high rates of unmet needs in the past month. CONCLUSIONS: Consumer-directed PAS enhances outcomes for many persons with disabilities. Self-reported outcomes are affected by many factors that could be addressed in PAS program development. PMID- 17852214 TI - Rehabilitation medicine in countries of Central/Eastern Europe. AB - PURPOSE: To describe attributes of rehabilitation medicine common to the five countries of Central Eastern Europe (CEE) and their implications for future challenges. METHODS: Critical collection and study of pertinent data on evolvement and present state of rehabilitation medicine in CEE countries by a coordinated team of rehabilitation experts from each of the relevant countries. RESULTS: CEE countries are similar in their need for rehabilitation medicine, its evolvement, present state and current practice. Settings largely emerged without strategic planning on the national level and lagged behind those in Central and Western Europe both in time and content. CONCLUSION: The framework that evolved in all except Slovenia is not appropriate to needs. In order to meet future challenges all five CEE countries need the incorporation of inpatient, outpatient and community-based rehabilitation into one system. PMID- 17852215 TI - The usage of functional wrist orthoses in patients with rheumatoid arthritis. AB - OBJECTIVE: To describe the usage of functional wrist orthoses and to identify factors contributing to usage in patients with rheumatoid arthritis (RA). METHODS: A multicentre, cross-sectional study, including a random selection of patients with RA visiting outpatient clinics. A total of 240/362 eligible patients (66%) completed questionnaires, a semi-structured interview and a clinical assessment. Usage was registered according to eight categories ranging from 'always' to 'never'. Factors potentially associated with usage included demographic variables, the presence of wrist and hand complaints, general disease characteristics, mental and physical functioning, coping strategies and satisfaction with functional wrist orthoses. Logistic regression analyses were used to determine which factors were associated with the usage of wrist splints. RESULTS: One hundred twenty-eight patients (53%) possessed functional wrist orthoses, whereas 74/128 (58%) were actually using them. Patients used them mainly during house keeping and cycling/driving. Main reasons for using the orthoses were relief of pain and joint protection, and main reasons for not using them were no need and problems with ease of use. Factors significantly associated with usage included the presence of wrist and hand complaints, worse physical functioning and greater satisfaction with comfort of the wrist orthoses. CONCLUSION: About half of patients with RA possessed functional wrist orthoses, with 58% of them actually being used. Apart from local complaints and general functional ability, satisfaction with comfort of the functional wrist orthoses appears to be an important factor for their usage. These results point at the need for additional research regarding modifiable factors associated with compliance, such as comfort and ease of use. PMID- 17852216 TI - Robotic gait trainer in water: development of an underwater gait-training orthosis. AB - PURPOSE: To develop a robotic gait trainer that can be used in water (RGTW) and achieve repetitive physiological gait patterns to improve the movement dysfunctions. METHOD: The RGTW is a hip-knee-ankle-foot orthosis with pneumatic actuators; the control software was developed on the basis of the angular motions of the hip and knee joint of a healthy subject as he walked in water. Three dimensional motions and electromyographic (EMG) activities were recorded in nine healthy subjects to evaluate the efficacy of using the RGTW while walking on a treadmill in water. RESULTS: The device could preserve the angular displacement patterns of the hip and knee and foot trajectories under all experimental conditions. The tibialis anterior EMG activities in the late swing phase and the biceps femoris throughout the stance phase were reduced whose joint torques were assisted by the RGTW while walking on a treadmill in water. CONCLUSION: Using the RGTW could expect not only the effect of the hydrotherapy but also the standard treadmill gait training, in particular, and may be particularly effective for treating individuals with hip joint movement dysfunction. PMID- 17852217 TI - Experience of physical activity in patients with fibromyalgia and chronic widespread pain. AB - PURPOSE: Patients with fibromyalgia (FM) and chronic widespread pain (CWP) find physical activity troublesome. The purpose was to develop a questionnaire to investigate the experience of physical activity in FM and CWP populations. METHOD: A questionnaire was developed from a qualitative study. After that, a total of 204 patients with FM or CWP completed the questionnaire. A factor analysis was conducted and the internal consistency was investigated. The relationship between the factors and pain, health status (the Fibromyalgia Impact Questionnaire, FIQ), distress (the Hospital Anxiety and Distress scale, HAD) and leisure time physical activity (the Leisure Time Physical Activity Instrument, LTPAI) was investigated. RESULTS: Five factors were identified: Physical Relaxation (PR), Well-being (WB), Activity Beliefs (AB), Activity-related Symptoms (AS) and Activity Habits (AH). Cronbach's alpha ranged from 0.57 to 0.86. The PR showed a correlation (rho 0.28, p < 0.01) with the FIQ Pain. The AS showed a correlation (rho 0.25, p < 0.01) with the FIQ total score, while the AH showed a correlation with the HAD Depression (0.26, p < 0.01) and with strenuous physical activity (LTPAI) (-0.32, p < 0.01). CONCLUSION: A new instrument was developed to study the experience of physical activity in persons with long lasting pain. Five factors were identified using factor analysis, and three of them showed fair associations with FM symptoms, distress or physical activity. PMID- 17852218 TI - Towards a biopsychosocial framework of osteoarthritis of the knee. AB - Research into the causes of osteoarthritis (OA) of the knee has traditionally followed a biomedical approach whereby the disease development and progression is regarded as an internal physiological process. As a result, treatment has focused on symptom reduction with limited modification of psychosocial variables. In fact, psychosocial factors such as environment and employment play a substantial role in the disease process and are important determinants of the overall level of disability of affected individuals. Thus, by placing greater importance on the biomedical aspects of knee OA, a complete representation of the health condition cannot be achieved thereby limiting treatment effectiveness. The purpose of this clinical commentary is to provide a rationale for the implementation of a biopsychosocial model of knee OA that can aid in more effective research and treatment for the disorder. PMID- 17852219 TI - Force production and EMG activity of neck muscles in adolescent headache. AB - PURPOSE: This study compared the maximal force, EMG/force ratio and co-activation characteristics of the neck-shoulder muscles between 30 adolescents with migraine type headache, 29 with tension-type headache, and 30 headache-free controls. METHOD: Force was measured with surface electromyography (EMG) from the cervical erector spinae (CES), the sternocleidomastoid (SCM) and trapezius muscles during the maximal isometric neck flexion, neck extension and shoulder flexion. RESULTS: Girls with migraine-type headache had higher EMG/force ratios between the EMG of the left agonist SCM muscle and the corresponding maximal neck flexion (p = 0.030) and neck rotation force to the right side (p = 0.024) than the girls with tension-type headache. Migrainous girls had more co-activation of right antagonist CES muscle during maximal neck flexion force than the girls without headache (p = 0.015). Neck force production showed no significant differences between girls. Girls with tension-type headache displayed lower left shoulder flexion force than girls with migraine-type headache (p = 0.005) or with no headache (p = 0.005). In boys, no significant differences were observed. CONCLUSIONS: Girls with tension-type headache and migraine-type headache have differences in neuromuscular function in the neck-shoulder muscles. The data amplify our knowledge of the neck-shoulder muscle dysfunction in adolescent headache, and may encourage the use of specific rehabilitation methods in the management of different types of headache. PMID- 17852220 TI - Daily occupations--performance, satisfaction and time use, and relations with well-being in women with limited systemic sclerosis. AB - PURPOSE: To describe activity level, operationalized as ADL capacity and performance of occupations, and occupational balance, operationalized as time use and satisfaction with occupations, in women with limited systemic sclerosis, and to investigate the relationship between these occupational factors and disease characteristics, demographic variables and wellbeing. METHOD: Forty-four women of working age and with long-standing limited systemic sclerosis were assessed regarding occupational factors, clinical variables, sociodemographic characteristics and well-being. RESULTS: The women exhibited a generally high activity level and were satisfied with their daily occupations. More time spent working was related to spending less time on household chores, greater satisfaction with occupations in general and greater well-being. Symptoms such as breathlessness, fatigue and pain, influenced ADL capacity and satisfaction with occupations negatively. CONCLUSIONS: Work seems to be an important factor for satisfaction with occupations and well-being. This emphasizes the importance of investigating risk factors for work disability in people with systemic sclerosis, and of developing strategies for people with a work disability to enable them to maintain routines and a structured day. The findings also demonstrate the importance of reinforcing performance in satisfying occupations in order to maintain a feeling of well-being. PMID- 17852221 TI - Social Security Disability Insurance (SSDI) in Parkinson's disease. AB - OBJECTIVE: Parkinson's disease (PD) causes significant economic burden for patients and caregivers. Social Security Disability Insurance (SSDI) provides insurance to workers in the United States who have been gainfully employed, but who are no longer able to work due to a medical condition. We performed a descriptive pilot study that examined PD patients' experience with SSDI. METHODS: PD patients who were diagnosed with PD prior to age 60 and were followed at an academic movement disorders center were consecutively invited to participate in a survey concerning their employment history and experience with SSDI. RESULTS: All 68 invited patients participated in the study (mean age 58 years, mean disease duration 9.5 years). Eighty-two percent of patients felt that they were too disabled to work full time at a mean of 3.4 years after PD diagnosis. Patients applied for SSDI at a mean of 5 years after diagnosis, and two-thirds of PD patients who applied for SSDI obtained it on their first attempt. The primary debilitating symptom that subjectively contributed to work disability was fatigue (49% of patients). Patients who successfully acquired SSDI had extensive documentation of physician visits, and the aid of a disability lawyer. CONCLUSIONS: Patients felt they were too disabled to work full time at a mean of 3.4 years after diagnosis. Those who applied for SSDI did so at a mean of 5 years after diagnosis. Patients who obtained SSDI awards had extensive documentation of medical records or the help of a disability lawyer. PMID- 17852222 TI - Medical and social aspects of the life course for adults with a skeletal dysplasia: a review of current knowledge. AB - PURPOSE: The paper examines the general literature and available research evidence on medical, health and social aspects of life for adults with skeletal dysplasia conditions causing profound short stature. METHOD: The paper reports on a literature review using available medical, psychological and social sources. RESULTS: There is a dearth of methodologically sound research evidence in this field, and this is particularly marked in areas such as transition to adulthood, ageing and medical, surgical and health experiences. CONCLUSIONS: There are serious gaps in the available literature and research evidence is sparse and often based on biased samples of limited numbers. This means that it is difficult to get information beyond the anecdotal in assessing the health and social needs of this group of people, and in particular to define needs that are currently unmet. It also limits the scope of advice and information available to health professionals and others in the field who offer support to adults with the conditions and parents of newly-diagnosed babies and young children. PMID- 17852223 TI - Evaluation of virtual shopping in the VMall: comparison of post-stroke participants to healthy control groups. AB - OBJECTIVE: To investigate the potential use of the VMall as an evaluation tool for rehabilitation by (1) describing its use with 14 post-stroke participants and (2) by comparing performance within the VMall of the post-stroke participants to healthy control participants. DESIGN: Criterion standard. SETTING: University of Haifa and the Chaim Sheba Medical Center. PARTICIPANTS: Fourteen post-stroke participants and 93 healthy participants from three age groups (children, young adults and older adults). PROCEDURE: The participants experienced the VMall and shopped for four grocery items and then completed feedback questionnaires. MAIN OUTCOME MEASURES: The experience of the stroke participants is described in detail. The duration and number of mistakes made during a four-item shopping task within the VMall, overall feedback, and perceived exertion. RESULTS: Significant differences were found between each of the three healthy groups and the stroke group for the mean total time to shop (F(3,97) = 23.28, P < 0.000). The participants' overall feedback on the VMall was positive with no differences between the groups. CONCLUSIONS: The VMall as used with the four-item shopping task was found to significantly differentiate between healthy to stroke participants. The shopping task was challenging for the stroke participants which have positive implications for treatment effectiveness. PMID- 17852224 TI - Become your own advocate: advice from women living with scleroderma. AB - PURPOSE: Systemic sclerosis (SSC) affects 300,000 people in the USA and has a significant effect on an individual's functional ability. The purpose of this study was to outline the key components of living with the illness and to identify the information that those who are newly diagnosed would need to initiate a successful course of disease self-management. The results will provide the groundwork for development and testing of a self-paced education program for patients with SSC. METHOD: Focus groups were conducted with 11 women diagnosed with SSC. RESULTS: Analysis of the transcripts yielded three themes, Secure Effective Medical Management, Live Your Life, and Learn Everything You Can. The thread Become Your Own Advocate wove these three themes together and illustrated that taking control of SSC is ultimately a function of self-advocacy. CONCLUSION: For patients with SSC, taking control of their illness was a necessary component of maintaining the highest quality of life possible. A positive attitude, a strong support system, a commitment to moving forward with life, and access to high-quality, timely information all provided the participants with the tools to develop and implement a strategy of self-advocacy in disease management. PMID- 17852225 TI - Validation of the human activity profile in stroke: a comparison of observed, proxy and self-reported scores. AB - PURPOSE: To assess the concurrent validity of the Human Activity Profile (HAP) with stroke and healthy control individuals, when reported by the subject or a proxy and compared to observed performance, used as gold standard; factors related to discrepancies; as well as to determine variables that could best predict physical activity levels. METHODS: A total of 24 stroke and 23 healthy control subjects took part in the study. Functional outcome measures included personal/demographic factors, HAP, the 10-meter walk, and cognition. RESULTS: Strong relationships were found between self-reported and observed scores for both groups (r=0.89-0.99). The relationships between proxy and observed scores were acceptable for stroke (r=0.80-0.87) but lower for control subjects (r=0.65 0.75), with intraclass correlation coefficients (ICCs) ranging from 0.69-0.89. Significant differences were found between proxy and observed scores for stroke, but not for control subjects. Discrepancies between scores showed little predictability from selected variables. For stroke subjects, the strongest variable explaining physical activity levels was walking speed (r2=43%) and the best combination of variables was walking speed plus cognition (r2=55%). CONCLUSIONS: Self-reported HAP was an excellent measure both for stroke and control subjects and related well to observed performance. Proxy reports appear to be valid for stroke subjects. HAP was significantly related to measures of walking speed. PMID- 17852226 TI - Outpatient spinal cord injury rehabilitation: managing costs and funding in a changing health care environment. AB - PURPOSE: To examine the literature describing the cost of outpatient rehabilitation for patients with spinal cord injury (SCI) as well as the effect of funding type on cost and outcome. A SCI rehabilitation planning and funding model is presented that calls for structured assessment of the client's economic environment, with follow through to promote full access to funding for rehabilitation plans. METHOD: Literature review of specific outpatient rehabilitation intervention costs and effect of funding type, followed by development of a funding model to improve access to available funding for SCI rehabilitation. RESULTS: There is insufficient economic data to draw conclusions about the relationship between an individual's rehabilitation needs and access to appropriate funding for outpatient rehabilitation. Consequently, health providers and payers need to adopt an approach that will improve consistency of payment decisions and access to necessary funding for rehabilitation. CONCLUSIONS: A model for a more formal approach to: (a) Assessment of a client's economic environment; (b) use of evidence-based SCI rehabilitation; and (c) use of available financial resources should promote better access to appropriate rehabilitation following SCI. PMID- 17852227 TI - Daily functioning of dyspnea, self-esteem and physical self in patients with moderate COPD before, during and after a first inpatient rehabilitation program. AB - PURPOSE: Inpatient rehabilitation improves dyspnea and increases self-esteem between admission and discharge in patients with moderate chronic obstructive pulmonary disease (COPD). Some researchers nevertheless argue that the changes may be due to nursing effects and thus that scores will decrease quickly at home after discharge. This study assessed the change in dyspnea, self-esteem and physical self mean scores and stability in patients with moderate COPD during three consecutive four-week periods: at home, during an inpatient rehabilitation program, and again at home post-discharge. METHODS: Twenty-three consecutive patients [63.9 years (SD 6.6)] with moderate COPD [FEV1 = 55.8% (SD 13.2)] were included. The participants responded to the Physical Self Inventory and rated dyspnea using a visual analogue scale twice a day. Exercise tolerance was assessed with the six-minute walk test (6MWT) at admission and discharge. RESULTS: 6MWT performance improved between admission and discharge [452.3 m. (SD 74.0) vs. 503.3 m. (SD 80.4), p < 0.001]. Dyspnea ratings improved (p < 0.001), as did the self-esteem and physical self scores between the two home periods (p < 0.001). The group showed less instability (SD and range) in their assessments of physical self-worth at home post-discharge compared to pre-admission (p < 0.01). Before rehabilitation, the correlation coefficients between dyspnea, and self esteem, the perceptions of physical condition and attractive body were all significant. After rehabilitation, the coefficients between dyspnea, and perceived physical condition, physical strength and sport competence were significant (p < 0.05). CONCLUSIONS: The results suggest that a first rehabilitation program increases the mean physical self scores in patients with moderate COPD and decreases their instability; the program also improves dyspnea. However, the impact of rehabilitation was greater on specific perceptions of physical abilities than on the global self-esteem. Randomized controlled trials are needed to confirm these changes, which were probably due to rehabilitation program. PMID- 17852228 TI - Postoperative hand therapy in Dupuytren's disease. AB - BACKGROUND: Postoperative hand therapy in patients after surgery for Dupuytren's contracture is common medical practice to improve outcomes. Until now, patients are referred for postoperative hand rehabilitation on an empirical basis. PURPOSE: To evaluate whether referral criteria after surgery because of Dupuytren's disease were actually adhered to, and, to analyse differences in outcomes between patients who were referred according to the criteria (correctly referred) and those who were not referred but should have been (incorrectly not referred). METHODS: Referral pattern was evaluated prospectively in 46 patients. Total active/passive range of joint motion (TAM/ TPM), sensibility, pinch force, Disability Arm Shoulder Hand questionnaire (DASH) and Michigan Hand outcomes Questionnaire (MHQ) were used as outcome measures preoperatively and 10 months postoperatively. RESULTS: In total 21 patients were referred correctly and 17 patients were incorrectly not referred. Significant improvements on TAM/TPM, DASH and MHQ were found at follow-up for the total group. No differences in outcomes were found between patients correctly referred and patients incorrectly not referred for postoperative hand therapy. CONCLUSION: Referral criteria were not adhered to. Given the lack of differences in outcomes between patients correctly referred and patients incorrectly not referred, postoperative hand therapy in Dupuytren's disease should be reconsidered. PMID- 17852229 TI - Identification of risk factors related to perceived unmet demands in patients with chronic stroke. AB - PURPOSE: To investigate the prevalence of unmet demands concerning autonomy and participation and to identify risk factors related to these unmet demands in patients with chronic stroke. METHOD: A cross-sectional study of 147 patients three years after stroke. We assessed perceived unmet care demands in relation to problems of participation and autonomy measured by the Impact on Participation and Autonomy Questionnaire (IPAQ). Socio-demographic and health characteristics were analysed as potential risk factors for the prevalence of unmet demands, using multivariate regression analysis. RESULTS: A total of 33% of the patients perceived at least one unmet demand in one of the IPAQ subdomains. Risk factors significantly related to the presence of unmet demands were younger age, motor impairment, fatigue and depressive symptoms. Findings indicate that the model including these factors was fairly accurate in identifying patients having unmet demands and those not having unmet demands. CONCLUSIONS: Unmet care demands were present in a substantial proportion of the stroke patients. The risk factors identified are helpful for clinicians and health care providers to recognize patients who are at risk of perceiving unmet care demands and to optimize care to patients with chronic stroke. PMID- 17852230 TI - The Spinal Cord Independence Measure (SCIM) version III: reliability and validity in a multi-center international study. AB - PURPOSE: To examine the third version of the Spinal Cord Independence Measure (SCIM III) for reliability and validity in a multi-center cohort study. METHOD: Four hundred and twenty-five patients with spinal cord lesions from 13 spinal cord units in six countries from three continents were assessed with SCIM III and the Functional Independence measure (FIM) on admission to rehabilitation and before discharge. RESULTS: Total agreement between raters was above 80% in most SCIM III tasks, and all kappa coefficients were statistically significant (P<0.001). The coefficients of Pearson correlation between the paired raters were above 0.9, and intraclass correlation coefficients were above 0.94. Cronbach's alpha was above 0.7. The coefficient of Pearson correlation between FIM and SCIM III was 0.790 (P<0.01). SCIM III was more responsive to changes than FIM in the subscales of Respiration and sphincter management and Mobility indoors and outdoors. CONCLUSIONS: The results support the reliability and validity of SCIM III in a multi-cultural setup. Despite several limitations of the study, the results indicate that SCIM III is an efficient measure for functional assessment of SCL patients and can be safely used for clinical and research trials, including international multi-center studies. PMID- 17852231 TI - Vegetative and minimally conscious state(s) survey: attitudes of clinical neuropsychologists and speech and language therapists. AB - PURPOSE: To gauge the understanding and opinions of clinical neuropsychologists and speech and language therapists (SLT) in relation to vegetative (VS) and minimally conscious (MCS) patients relative to available practice guidelines. METHOD: Semi-structured questionnaires were sent to all UK Practitioner Full Members of the BPS Division of Neuropsychology (307) and SLT managers (371) in March to April 2002 examining post qualification clinical practice, professional family involvement and views on neuro-rehabilitation access. Difference(s) in clinical practice among clinical neuropsychologists and SLTs were observed. RESULTS: Some 27% returned questionnaires (n=184). Despite significant working experience, most respondents poorly defined both VS and MCS. Among clinical neuropsychologists and speech and language therapists not working with these patients, less positive attitudes regarding the value of neuro-rehabilitation were endorsed. CONCLUSIONS: Despite the development of SMART training for VS, there is a dearth of specific training in MCS assessment and management. The need to improve professional understanding among these staff groups is highlighted. PMID- 17852232 TI - To regain participation in occupations through human encounters--narratives from women with spinal cord injury. AB - PURPOSE: To gain an understanding of how women with spinal cord injury (SCI) experienced human encounters in occupations and how these influenced their participation. METHOD: The data were collected through two or three in-depth interviews with 13 women (age 25-61 years) with SCI. Data analysis was carried out by using a paradigmatic analysis of narrative data, followed by an interpretation based on a narrative theory. RESULTS: The results showed a complexity where the women's experiences and acting in human encounters changed over time. In these human encounters the women struggled with conflicts, supported other persons that were insecure and revaluated their apprehension about persons in their social network. These multidimensional human encounters thereby enabled them to regain participation in occupations. CONCLUSIONS: This shows that human encounters are important for persons with disabilities so they can restructure their occupational identity and their needs for participation in occupations. The study also showed that the use of narratives as a tool within rehabilitation could lead to an increased understanding of the subjective changes that occur over time for a person with a disability. PMID- 17852233 TI - Guidelines for prevention of venous thromboembolism in immobile patients secondary to neurological impairment. AB - BACKGROUND: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in hospitalized patients and 7% of these cases are due to immobility secondary to a neurological impairment. Many guidelines are available to guide clinicians dealing with medical or surgical patients. However, and with the exception of spinal injuries, no guidelines are available to deal with other neurologically impaired patients at risk of VTE. AIM: Our study aimed at gathering evidence from the literature to enable us to deal with the main controversial issues of VTE prevention. Guidelines will be formulated. METHOD: A Clinical Standards Group is responsible for the development of clinical guidelines for the Greater Manchester Neurorehabilitation network with services covering a population of around 3 million. The development of VTE prevention guidelines started with the formulation of the main questions, then gathering evidence from the literature to address these questions. Wide consultation then took place. The guidelines were then put before the group for endorsement. RESULTS: Answers for the main questions such as duration of thromboprophylaxis, TEDS and antiplatelets drugs use were suggested. The resulting document was summarized as a flow chart for use. CONCLUSION: We feel that the proposed guidelines are a useful tool for clinicians as they reflect the evidence available from the literature at the moment. PMID- 17852234 TI - Blending activity and participation sub-domains of the ICF. AB - OBJECTIVE: The objective of the study was to test the supposition that distinct Activity and Participation sub-domains of the International Classification of Functioning, Disability, and Health (ICF) could be identified using physical function questionnaire items drawn from the Activity and Participation Measures for Post Acute Care. DESIGN: A cross-sectional survey design was employed. Subjects. The sample consisted of 272 patients who had received post acute care across inpatient and community care settings during the previous year. METHODS: Exploratory factor analysis with oblique rotation was used to identify interpretable dimensions underlying 83 physical functioning questionnaire items. RESULTS: Factor analysis findings revealed five distinct ICF conceptual sub domains that explained 61% of the total variance of the data, with root mean square residual equal to 0.089. These domains were labeled: (i) Daily activity, (ii) Applied cognitive, (iii) Role participation, (iv) Mobility, and (v) Social participation. These five factors were correlated to varying degrees and achieved acceptable levels of internal consistency with coefficient alphas from 0.59-0.93. CONCLUSION: These analyses suggest that clear distinctions between Activity and Participation sub-domains of the ICF could not be identified in a sample of adults who had recently received post acute care. We believe this is important evidence of the ability to measure blended Activity and Participation sub-domains that cut across distinct and interpretable areas of life functioning. PMID- 17852235 TI - Injury among 1107 Canadian students with self-identified disabilities. AB - PURPOSE: Students with disabilities are at risk for poor health outcomes; however, the causes and consequences of injury in this group are not well understood. The epidemiologies of injuries among students with and without disabilities were profiled and compared. METHODS: The cross-sectional, 2002 Health Behaviour in School-aged Children Survey, was administered to a representative sample of 7235 students (grades 6-10) from Canada. Students who reported at least one functional difficulty due to a health condition were classified as having a disability. Primary outcomes were: (i) Medically attended injury; (ii) multiple injuries, and (iii) serious injury experiences during a 12 month period. RESULTS: Some 16.3% of students reported a disability. Injuries were more common in students with disabilities compared to those without disabilities (67% vs. 51% annually, p < 0.01). Students with disabilities experienced 30% increases in the risk for medically attended injury, multiple injury, and serious injury as compared to their peers. Consistent and statistically significant associations (p < 0.05) were identified between different types of disability and all injury outcomes. CONCLUSIONS: Canadian students who report disabilities experience higher risks for injury than their peers, perhaps due to an inability to perceive and avoid environmental hazards. Injury prevention programmes are needed to address these unique risk profiles in order to prevent additional disability or secondary conditions. PMID- 17852237 TI - The utility of ICF for describing interaction in non-speaking children with disabilities--caregiver ratings and perceptions. AB - PURPOSE: The purpose of the study is to explore the utility of the International Classification of Functioning, Disability and Health (ICF) when assessing caregivers' perceptions of interaction and factors related to interaction in non speaking children with disability. METHOD: A questionnaire with focus on interaction and related factors was constructed by linking questions in existing instruments to ICF and was completed by 208 professionals and parents of 195 non speaking children with disabilities in Russia. Caregivers' descriptions of interaction in open-ended questions were qualitatively analysed and compared to selected caregivers' ratings of children's functioning and environment in the questionnaire based on ICF. RESULTS: In the open-ended questions about interaction the caregivers described modes of communication children used, situations in which interactions took place, positive and negative aspects of interactions. Thirty eight respondents described interaction with children negatively, 66 neutrally, and 76 positively. Statistical analyses revealed significant differences among the three groups of respondents concerning their ratings of children's functioning and environment in the ICF-based questionnaire. CONCLUSIONS: The ICF-related items in the questionnaire corresponded to caregivers' perceptions of interaction, which shows their relevance for the description of interactions. ICF is feasible in describing of interaction and interaction-related factors in non-speaking children with disabilities in Russia. PMID- 17852238 TI - Identity related to living situation in six individuals with congenital quadriplegia. AB - PURPOSE: This study was a preliminary examination of structural aspects of identity, particularly identity associated with living situation, in individuals who have quadriplegia due to cerebral palsy. METHOD: A hierarchical classes algorithm (HICLAS) was used to construct idiographic 'identity structure' models for three individuals who are living in an inpatient hospital setting and for three individuals living in community-based group residences. RESULTS: Indices derived from the models indicate that the identity 'myself as one who has a disability' was structurally superordinate (i.e., resided at a high hierarchical level) for all six participants, suggesting a high level of importance of this identity in participants' sense of self. The models also indicate that while identity associated with one's particular living situation was superordinate for persons living in the hospital, it was not for persons living in community residences. CONCLUSIONS: While conclusions based on this small sample are necessarily limited, the data suggest that identity associated with living situation might differ in structural centrality, and presumably subjective importance, for persons living in inpatient versus community-based settings. PMID- 17852239 TI - Women with Disabilities: cultural competence in rehabilitation psychology. AB - Women with Disabilities represent a cultural group with specific issues. Rehabilitation psychologists are encouraged to familiarize themselves with some of those issues in order to deliver culturally relevant treatment. An overview is provided of psychological guidelines for attending to cultural issues in assessment, treatment, and research. Broad issues faced by Women with Disabilities are described. Disability-specific safety concerns are discussed with attention to ways in which they might be addressed by rehabilitation psychologists. PMID- 17852240 TI - The complex array of antecedents of depression in women with physical disabilities: implications for clinicians. AB - PURPOSE: This article discusses the complex interrelation of elements of the physical, psychological, social, and environmental life context of women with physical disabilities and the association of these elements with significant disparities in rates of depression and access to mental health care for this population. METHODS: Literature and concept review. RESULTS: High rates of depression in women with physical disabilities are well documented in the literature. Many elements that are disproportionately common in the lives of women with physical disabilities, including socio-economic disadvantage, functional limitations, pain and other chronic health conditions, poor diet, physical inactivity, smoking, violence, low self-esteem, sexuality problems, chronic stress, environmental barriers, and barriers to health care, have also been linked with higher rates of depression and depressive symptomatology. Depression self-management interventions tailored for women with disabilities have been developed and proven effective. CONCLUSIONS: Many women who must deal with the stresses surrounding an array of health problems may experience symptoms of depression without necessarily meeting the criteria for clinical depression. Psychologists, counselors, primary care physicians, specialists, and other medical and rehabilitation professionals are challenged to recognize the symptoms of depression in women with physical disabilities and assist them in obtaining appropriate psychological and pharmacological interventions. PMID- 17852241 TI - The transition from hospital to home for individuals with acquired brain injury: a literature review and research recommendations. AB - PURPOSE: To review the literature relating to the transition from hospital to home for individuals with acquired brain injury (ABI) and make recommendations concerning the future direction of transition-specific research. METHOD: Relevant research articles were identified through searching existing database systems and by reviewing the reference lists of identified articles. Only articles in which the results directly related to individuals with ABI from the time of discharge to 1 year post-discharge were included in the review. RESULTS/DISCUSSION: A total of 50 articles were identified as meeting the criteria for inclusion in the review. The methodological quality of included articles was evaluated using a set of specific criteria. The articles were classified into the following categories: (i) The perspectives of individuals with ABI and their caregivers; (ii) outcomes for individuals with ABI following transition; (iii) post-discharge services; and (iv) transitional living services/programmes. The majority of articles were based on samples of individuals with stroke, typically aged over 65 years. A common theme identified in the review was that the transition from hospital to home is typically perceived as an exciting yet difficult period for individuals and their families and as such, post-discharge support is critical. CONCLUSION: Further ABI transition-specific research is necessary in order to: (i) Develop a comprehensive theoretical framework of the transition phase; and (ii) facilitate both the validation of current intervention strategies and the development of innovative/tailored intervention approaches. PMID- 17852243 TI - A survey of Australian adult users of altered auditory feedback devices for stuttering: use patterns, perceived effectiveness and satisfaction. AB - PURPOSE: Small portable devices that provide delayed auditory feedback (DAF) and/or frequency altered feedback (FAF) have been developed and marketed to clinicians and people who stutter as fluency enhancing aids for use in everyday speaking situations. The literature contains many laboratory-based reports about the impact of altered auditory feedback (AAF) on the speech of people who stutter but few reports about its use in everyday speaking situations. This paper investigates use patterns and perceptions of the effectiveness and satisfaction with AAF devices. METHODS: The current study surveys 14 Australian AAF users. RESULTS: The survey responses revealed varied opinions about AAF devices and their use and effectiveness in everyday speaking situations. Opinions were somewhat related to the type of device used. CONCLUSIONS: The results of this study provide some important directions for future research. In particular there is need to investigate the effectiveness of AAF devices when used in conjunction with other traditional treatments. PMID- 17852244 TI - The Multiple Sclerosis impact Profile (MSIP). Development and testing psychometric properties of an ICF-based health measure. AB - PURPOSE: The aim of this study was to develop and test the structure of the Multiple Sclerosis Impact Profile (MSIP), and to evaluate its reliability and validity within a large group of MS patients. METHOD: Data were obtained from a postal survey of 377 patients attending the Groningen MS centre of the university hospital and 153 patients from the MS patients' association. RESULTS: Factor analysis showed that the MSIP comprised domains representing the four components of the International Classification (ICF). The body functions component comprised two factors, which we divided into three scales: 'muscles and muscle movement functions' (MMF), 'excretion and reproductive functions' (ERF) and 'mental functions' (MF). The activities component comprised one factor, which we divided into two scales: 'basic movement functions' (BMF) and 'activities of daily living' (ADL). The participation component comprised one factor: 'participation in life situations' (PLS). The environmental factors component comprised one factor: 'environmental factors' (EF). Four clinically relevant 'symptom' items were added to the questionnaire as single items. The MISP scales yielded sufficient to good internal consistency coefficients. Analysis of the convergent, divergent and known-groups validity indicated that the MSIP measures the physical, psychological and social impact of MS and discriminates between categories of course of disease and disease severity. CONCLUSION: The MSIP seems to be a reliable and valid ICF-based outcome measure that covers a broad range of clinically relevant aspects of health. ICF can play an important role in measurement development and improvement of a unified and standard language in clinical practice and research. PMID- 17852246 TI - Validity of the impact on participation and autonomy questionnaire: a comparison between two countries. AB - PURPOSE: To evaluate the cross-cultural validity of the five subscales of the Impact on Participation and Autonomy (IPA) measure and the full 31-item scale. METHOD: Data from two validation studies (Dutch and English) were pooled (n = 106). Participants (aged 18-75), known to rehabilitation services or GP practices, had conditions ranging from minor ailments to significant disability. Validity of the five subscales and the total scale was examined using Rasch analysis (Partial Credit Model). P values smaller than 0.01 were employed to allow for multiple testing. RESULTS: A number of items in all the subscales except 'Outdoor Autonomy' needed rescoring. One 'Indoor Autonomy' item showed uniform DIF by country and was split by country. One 'Work and Education' item displayed uniform and non-uniform DIF by gender. All the subscales fitted the Rasch model and were invariant across country. A 30-item IPA also fitted the Rasch model. CONCLUSION: The IPA subscales and a 30-item scale are invariant across the two cultures and gender. The IPA can be used validly to assess participation and autonomy in these populations. Further analyses are required to examine whether the IPA is invariant across differing levels of disability and other disease groups not included in this study. PMID- 17852247 TI - Transfemoral amputees' experiences of the first meeting and subsequent interactions with hospital staff. AB - PURPOSE: To describe, by use of a phenomenological approach, how transfemoral amputees experience their first meeting and subsequent interaction with hospital staff in the acute phase, in the long term and suggestions for future care giving. METHOD: Eleven transfemoral amputees, median age 33.5 years, were interviewed. The amputations, performed in median 7.5 years before the interview, were caused by tumour, motorcycle accidents or work-related traumas. The participants were community dwelling and managed well indoors. All, except one, worked or studied full time. The interviews were tape-recorded and transcribed verbatim. RESULTS: Three themes emerged: (i) Communication/information - limitations in preparing the patient for the new situation, (ii) empathy and emotional support, and (iii) ability to meet the need of individually tailored rehabilitation. For future care-giving three categories emerged: (i) Individually tailored communication/information, (ii) rehabilitation to be prepared to adapt to one's new situation, and (iii) support in regaining control. CONCLUSION: The participants expressed a need for both professional and emotional support in the acute phase. Over time they preferred a patient-centred approach which improved coping skills and facilitated their own ability to gain control. Increased awareness of how meeting and interacting with hospital staff influences rehabilitation processes may further improve patient satisfaction and outcomes. PMID- 17852248 TI - Preliminary evaluation of a multidisciplinary pain management program for children and adolescents with chronic musculoskeletal pain. AB - PURPOSE: To describe the outcome of a multidisciplinary pain management program for children and adolescents with chronic musculoskeletal pain. METHODS: STUDY DESIGN: exploratory retrospective cohort study. The study sample consisted of a cohort of 70 children and adolescents (age: 8-21 years) with chronic musculoskeletal pain who completed a 3-month inpatient multidisciplinary pain management program. The program consisted of graded physical exercises, graded activities and counseling of the children and their parents. Assessed were motor and social activities, pain intensity, global assessment of physical functioning and psychosocial well-being (by patient and physician), understanding of the pain process and reduction of medical consumption. Assessments were performed at pre admission, day of admission, day of discharge and at three months after discharge. Data collection took place over a 10-year period. RESULTS: Compared to admission, at discharge there were significant improvements in motor performances, school attendance, reduction of pain scores, understanding of the chronic pain process and reduction of medical consumption. Results remained stable at follow-up after three months. CONCLUSION: The results of this study indicate that a multidisciplinary pain management program for children and adolescents with chronic musculoskeletal pain may be effective. PMID- 17852249 TI - Unique aspects of women's emotional responses to disability. AB - PURPOSE: To improve rehabilitation clinicians' awareness of gender differences in emotional responses to disability as a means of enhancing accuracy and sensitivity in diagnosis and treatment of persons in their care. METHOD: A prospective survey study using a new grief measure, the Loss Inventory (LI), with a diverse convenience sample of persons undergoing inpatient rehabilitation in the USA. Focused review of the bereavement, depression, and disability literatures related to observed gender differences. RESULTS: Study participants reported grief symptoms in varying intensities. Consistent with all literature reviewed, significant gender differences were found in kind and intensity of grief and depression symptoms reported. Ethnicity also significantly affected responses to disability by LI study participant responses. CONCLUSIONS: While persons with disabilities as a whole may not necessarily develop depression, gender is a risk factor for onset of mood problems after illness or injury related losses. As compared with study sample disabled men, disabled women reported more intense and different symptoms of grief and depression. Women with disabilities in the LI sample were twice as likely as disabled men to be depressed. Rehabilitation clinicians may wish to incorporate consideration of these differences in their mental health assessments, diagnoses, and treatment plans. PMID- 17852252 TI - Working after a stroke: survivors' experiences and perceptions of barriers to and facilitators of the return to paid employment. AB - PURPOSE: This paper examines respondents' relationship with work following a stroke and explores their experiences including the perceived barriers to and facilitators of a return to employment. METHOD: Our qualitative study explored the experiences and recovery of 43 individuals under 60 years who had survived a stroke. Participants, who had experienced a first stroke less than three months before and who could engage in in-depth interviews, were recruited through three stroke services in South East England. Each participant was invited to take part in four interviews over an 18-month period and to complete a diary for one week each month during this period. RESULTS: At the time of their stroke a minority of our sample (12, 28% of the original sample) were not actively involved in the labour market and did not return to the work during the period that they were involved in the study. Of the 31 participants working at the time of the stroke, 13 had not returned to work during the period that they were involved in the study, six returned to work after three months and nine returned in under three months and in some cases virtually immediately after their stroke. The participants in our study all valued work and felt that working, especially in paid employment, was more desirable than not working. The participants who were not working at the time of their stroke or who had not returned to work during the period of the study also endorsed these views. However they felt that there were a variety of barriers and practical problems that prevented them working and in some cases had adjusted to a life without paid employment. Participants' relationship with work was influenced by barriers and facilitators. The positive valuations of work were modified by the specific context of stroke, for some participants work was a cause of stress and therefore potentially risky, for others it was a way of demonstrating recovery from stroke. The value and meaning varied between participants and this variation was related to past experience and biography. Participants who wanted to work indicated that their ability to work was influenced by the nature and extent of their residual disabilities. A small group of participants had such severe residual disabilities that managing everyday life was a challenge and that working was not a realistic prospect unless their situation changed radically. The remaining participants all reported residual disabilities. The extent to which these disabilities formed a barrier to work depended on an additional range of factors that acted as either barriers or facilitator to return to work. A flexible working environment and supportive social networks were cited as facilitators of return to paid employment. CONCLUSION: Participants in our study viewed return to work as an important indicator of recovery following a stroke. Individuals who had not returned to work felt that paid employment was desirable but they could not overcome the barriers. Individuals who returned to work recognized the barriers but had found ways of managing them. PMID- 17852253 TI - The experiences of treatment from other people as narrated by people with moderate or severe traumatic brain injury and their close relatives. AB - PURPOSE: The aim of this study was to describe the treatment from other people as experienced by people with moderate or severe traumatic brain injury (TBI) and their close relatives. METHOD: Twelve people with moderate or severe TBI and eight of their close relatives were interviewed. The interviews were analysed using thematic content analysis. RESULTS: The results were described by the means of two themes: being excluded and missing confirmation. People with TBI and their close relatives had experiences of being avoided, being ruled by the authorities, being met with distrustfulness and being misjudged. They also searched for answers and longed for the right kind of help. People who listened to them, believed them and tried to understand and help them were appreciated. CONCLUSIONS: This study showed a lack of treatment which promotes well-being of the people with TBI and their close relatives. They experienced bad treatment also from authorities. Therefore, we emphasize that authorities should continuously reflect on how to make their practice a place which promotes dignity. Treatment of people with TBI and close relatives may be improved by increased knowledge about TBI, living with it and being a close relative to a person with TBI. This is a challenge to health care and rehabilitation professionals. PMID- 17852254 TI - Exploring ICF components in a survey among Xhosa speakers in Eastern & Western Cape, South Africa. AB - PURPOSE: To contribute to the testing and development of the ICF model by exploring the relationship between activity limitations, participation restrictions and environmental barriers. METHOD: Structured questionnaire-based interviews were carried out among a convenience sample of 950 households counting 4917 individuals in Eastern and Western Cape, South Africa. Approximately half of the households had at least one individual with disability, while the other half represented controls in the study. Activity limitations, participation restrictions and environmental barriers were operationalized by means of questions drawn directly from the ICF checklist. RESULTS: Principal component analyses supported a four-component solution for the activity and participation variables, and a two-component solution for the barrier variables. Scales for each sub-component were produced by adding the individual items under each sub component. Male respondents are more restricted than females when it comes to social activities, individual care, education and mobility barriers. While respondents in Western Cape scored higher (more limitations and restrictions) on the activity and participation sub-scales individual care, daily activities and education, Eastern Cape respondents scored higher on both the environmental barrier sub-scales. CONCLUSIONS: A viable structure of sub-components under the broader ICF concepts has been demonstrated. The study has provided some support to viewing activity limitations and participation restrictions as two independent dimensions, but also invites further studies and refinement of the model. PMID- 17852255 TI - The patient's view of recovery: an emerging tool for empowerment through self knowledge. AB - PURPOSE: To introduce Recovery Preference Exploration (RPE) as a new technique for studying the personal significance of being able to perform one type of functional activity over others. To determine if patients' concepts of function reflect the ADL, sphincter management, mobility and cognition (ASMC) domains established through the factor analyses of observed patient performance. METHODS: RPE involves an adapted card sort procedure. Patients sorted 18 cards each listing a single functional skill such as eating, walking, and memory into subjectively meaningful groups of activities based on how they see those skills relating to one another in their daily lives. They then ordered the groups from most to least important. Recovery preferences were explored for 32 patients with disabilities resulting from neurological or other conditions undergoing inpatient rehabilitation in the USA. RESULTS: The abilities to eat, bathe and toilet were the activities most frequently placed in the most valued pile. At times, the patient's card sorts mirrored the ASMC domains. At other times, patients grouped activities that tended to occur in a particular place or that were linked through cause and effect. Patients' narrative explanations reflected the uniqueness of their personal circumstances. CONCLUSIONS: RPE uncovers the life contexts that underlie patients' subjective beliefs about the meaning of being able to perform various types of activities. RPE might be applied in clinical practice and research to explore the idiosyncratic aspects of disability. PMID- 17852256 TI - Medically unexplained illness in short- and long-term disability applicants: prevalence and cost of salary reimbursement. AB - PURPOSE: Compared to patients with explained illness, patients with medically unexplained illness (MUI) may be at elevated risk of applying for disability. Accordingly, patients with MUI may account for a disproportionate number of disability claims and for a disproportionate percentage of salary reimbursement costs. The study was conducted to determine: (a) The prevalence of MUI among disability insurance claimants; (b) the cost of salary reimbursement; and (c) the impact of psychiatric comorbidity on length and cost of disability. METHOD: An insurance database of 26,451 short-term disability (STD) recipients with long term disability (LTD) coverage was analyzed to determine the prevalence and salary reimbursement costs of MUI. Applicants with medically explained and psychiatric illness were included for comparison. RESULTS: The prevalence of MUI among STD recipients was lower than clinical and community rates. Rates of application and receipt of LTD benefits for MUI were similar to explained illness. When LTD payments were projected to retirement age, costs associated with unexplained back pain and fibromyalgia were comparable to those of explained illness. The length of disability and salary reimbursement costs were greater when comorbid psychiatric illness was present. CONCLUSIONS: Patients with MUI did not account for a disproportionate number of disability claims or amount of the money spent on salary reimbursement. Comorbid psychiatric illness increased the length and cost of disability. PMID- 17852258 TI - REPAS, a summary rating scale for resistance to passive movement: item selection, reliability and validity. AB - PURPOSE: To establish: (i) item characteristics and item selection for the REPAS; (ii) internal consistency, inter-rater and test-retest reliability of the final REPAS version and its subtests; (iii) the association between the REPAS and selected other clinical scales of impairment and activity limitation. METHOD: Thirty-three neurological patients with central paresis. Two REPAS assessments with a one-week interval by two independent raters. Concurrent assessment of the Motricity Index, Box-and-Block test, Functional Ambulation Category, Timed walking, Barthel Index, Disability Rating Scale, Carer Burden Scale, and Hygiene Score. RESULTS: Twenty-six of 52 REPAS items fulfilled the item selection criteria. The final test version showed a high internal consistency, inter-rater and test-retest reliability (correlation coefficients: 0.87-0.97, no significant difference between raters or with test repetition). Reliability of the arm and leg subtests was substantial (correlation coefficients: arm subtest 0.63-0.98, leg subtest 0.56-0.96). REPAS scores were moderately associated with basic ADL competence and a carer's burden with arm or leg adductor spasticity. The REPAS, arm subtest scores, degree of arm paresis and gross manual dexterity showed a moderately high association. CONCLUSIONS: The Ashworth scale-based guidelines assured comparability of test administration and scoring. The REPAS is a reliable and valid summary rating scale for resistance to passive movement. PMID- 17852259 TI - Chronic low back pain: patients' experiences, opinions and expectations for clinical management. AB - PURPOSE: To explore the experiences, opinions and treatment expectations of chronic low back pain (LBP) patients in order to identify what components of treatment they consider as being of most value. METHOD: Three stand-alone focus groups were convened. All participants were experiencing chronic non-specific LBP (>3 months). Each group was facilitated by an independent moderator, and guided by a series of pre-determined questions. Participants were encouraged to freely air their personal opinions during the discussion. Transcribed data were organized into a series of 'categories' using the Qualitative Solutions for Researchers Nudist 6 package from which five common themes emerged. RESULTS: Each participant had typically experienced a variety of failed treatment approaches. Whilst the value of advice and exercise was recognized, participants typically questioned the appropriateness of such treatment given the fact that a precise diagnosis was rarely given, and symptoms often recurred. As a result, poor adherence with advice and exercise appeared to be a key factor limiting the potential effectiveness of long-term self-management strategies. CONCLUSIONS: Participants considered appropriate exercise (despite pain) and activity modification as important components for effective long-term self-management of symptoms. To enhance treatment effectiveness, participants welcomed the introduction of individually tailored advice and exercise programmes, with supervision and follow-up support, along with a better understanding of the physical and emotional impact of chronic LBP by practitioners. PMID- 17852260 TI - Reasons for recovery after stroke: a perspective based on personal experience. AB - PURPOSE: The purpose of this study was to learn more about individual beliefs and personal strategies used to support the period of recovery after stroke. It sought to identify the factors that were perceived to be enablers as well as challenges to recovery. Personal actions or experiences, which were perceived to be effective in influencing progress, would be identified. METHOD: Qualitative in depth interviews were carried out with 10 participants (mean age 61.8 years). Time following stroke onset ranged between 6 weeks and 13 months. All participants had some residual activity limitation and three participants had varying degrees of aphasia. The interviews were approximately 60 - 90 minutes and all data was subjected to content analysis. RESULTS: Analyses of interview data identified two main themes which were perceived to have influenced progress after stroke. The first related to internal factors such as personal control over progress, optimism and fears of dependency and the second included more external factors, such as the influence of therapeutic interactions and success with a specified marker of independence such as dressing, washing and walking. CONCLUSION: An important finding of this study was that individuals all identified a number of specific factors which had supported or hindered their own recovery. There were a diversity of both internal/personal and external factors which may not be surprising, given the complexity of stroke, but all participants stressed the importance of both factors. The findings from this study are preliminary and relate only to this particular group of participants, as such they cannot be generalizable to the stroke population as a whole. However, the interaction between the two themes identified requires further exploration, especially in relation to therapy which could have both a positive and negative influence on personal control. There is a clear need to understand how professionals can, in the first place, take time to identify each individual's preferences and personal goals and secondly, make sure that these are fully addressed in a planned treatment programme. This will ensure that progress in individuals after stroke is supported by professionals with a more eclectic, individualized approach. PMID- 17852261 TI - Organizing future research and intervention efforts on the impact and effects of gender differences on disability and rehabilitation: the usefulness of the International Classification of functioning, Disability and Health (ICF). AB - The International Classification of Functioning, Disability and Health (ICF) is discussed as being relevant to research and service delivery for women with disabilities. The personal meaning a disability has for a woman is shaped largely by Personal Factors. These, in turn, have historically been affected strongly by Environmental Factors such as culture and attitudes. Too often both Personal Factors, and how they are shaped by Environmental Factors, are not adequately addressed in our intervention programs. The interaction of Personal and Environmental Factors is illustrated by examples from the technology use and non use literature. PMID- 17852262 TI - Postnatal cerebral infection leading to hemiplegic cerebral palsy: clinical description of 13 children in Stockholm, Sweden. AB - PURPOSE: The aim of this research was to estimate the prevalence of postnatal cerebral infection leading to hemiplegic cerebral palsy (CP) in Stockholm County and to describe the motor impairments, associated impairments and involvement of the non hemiplegic side. METHOD: Children with hemiplegic CP subsequent to a cerebral infection in the perinatal period up to the age of seven years were identified. The assessments of child psychologists and speech therapists and EEG studies, CT-scan or MRI of the brain were extracted from the children's files. Thirteen children, with a mean age of 9.5 years, participated. The prevalence was 0.03/1000. RESULTS: Nine children suffered from mental retardation, seven took antiepileptic drugs and six had bilateral radiological anomalies. The non hemiplegic side was involved in six of the children. CONCLUSION: Cerebral infection at an early age can cause hemiplegic CP with a high frequency of associated impairments and with involvement of the non-hemiplegic side. The infectious origin probably gives rise to a more widespread brain injury. PMID- 17852263 TI - Psychosocial adjustment patterns of persons with spinal cord injury in Taiwan. AB - PURPOSE: The purpose of this study was to examine the psychosocial adjustment patterns of a community sample of persons with spinal cord injury in Taiwan. METHOD: A total of 102 participants were recruited from the Association of People with Spinal Cord Injury in Taipei City. Mean age of participants was 30.8 years (SD=11.39 years), and 77% were men. The participants were asked to complete a research packet containing a demographic questionnaire, the Psychosocial Adjustment to Illness Scale-Self Report Questionnaire, and the Sense of Coherence Questionnaire. RESULTS: Four distinct groups were found, representing different levels of psychosocial adjustment: (i) Well adjusted, (ii) Moderately adjusted, (iii) Moderately adjusted and sexually inexperienced, and (iv) Poorly adjusted. Employment status, age at the time of onset, injury level, and current age, as well as the motivational and behavioural aspects of coping, were identified as the functions discriminating the groups based on the demographic characteristics and sense of coherence, respectively. CONCLUSIONS: Vocational, sexual, and leisure areas of adjustment were found to be the most problematic for individuals with SCI in Taiwan. Counseling and other rehabilitation intervention efforts should focus on these identified needs of people with SCI in Taiwan. PMID- 17852264 TI - Urban/rural differences in health insurance coverage among people with multiple sclerosis. AB - PURPOSE: To present urban/rural analyses of health insurance coverage among people with multiple sclerosis (MS). This research also combined all survey respondents from each urban/rural area into one group of people with MS in health maintenance organizations (HMOs)/managed care and another group of people with MS who have other health insurance plans to compare any differences in coverage. METHODS: We interviewed 1,518 people with MS living in all 50 states. Survey results were analyzed using SPSS. RESULTS: Most people with MS in each urban/rural area had health insurance coverage (92-95%), with significant urban/rural differences observed in HMO/managed care enrollments. We found no urban/rural differences among people with MS in HMOs/managed care, or among people with MS with other health insurance plans, in satisfaction with coverage of routine care and MS-focused care, or with perceptions of how coverage enables utilization of health services. However, we found that people with MS in HMOs/managed care were more satisfied than people with MS with other health insurance with their coverage of routine care and perceived that their coverage enabled greater utilization of routine care and needed medications. CONCLUSIONS: We found no significant differences in satisfaction with MS-focused care or with perceptions of how well coverage enables utilization of MS-focused care or needed assistive devices between people with MS in HMOs/managed care and people with MS who have other health insurance. PMID- 17852265 TI - Posturographic testing and motor learning predictability in gymnasts. AB - PURPOSE: One aim of this study was to find if there was a difference between balance and stability between elite level gymnasts and non-gymnasts. Another aim was to find if there was a relationship between dynamic posturographic scores associated with sway fatigue or adaptability and the ability to learn new gymnastic routines. The ultimate aim of the study was to improve gymnastic performance while reducing the probability of injury. METHODS: Computer dynamic posturography (CDP) provided stability scores, fatigability ratios and adaptation ratios in elite level gymnasts and non-gymnasts controls. Relationships between the postural integrity of gymnasts and non-gymnasts were calculated. The gymnasts were trained in a novel gymnastic routine and performance outcomes were compared to the CDP outcomes. RESULTS: Tests of postural stability have shown that gymnasts have greater postural stability than non-gymnasts. Gymnasts whose adaptability scores were higher were able to learn and perform new motor routines better than those with lower adaptability scores or high fatigability ratios. CONCLUSIONS: While gymnasts have greater postural integrity than do non-gymnasts, CDP can identify individuals whose ability to perform new motor activities might be impaired. Methodology to improve functional stability not associated with the motor task may contribute to increased sports performance and decreased probability of injury. PMID- 17852266 TI - Characteristics of disability pensioners returning to work: an interview study among individuals with musculoskeletal disorders. AB - PURPOSE: To explore adaptation patterns among disability pensioners with musculoskeletal disorders returning to work by means of the Swedish law on 'resting disability pension'. METHOD: Qualitative analyses of interviews with 17 individuals going back to work. RESULTS: Three adaptation patterns were identified: The Go-getter, the Realist and the Indifferent. These differed regarding influence factors, own expectations, motive, morals and mentality. CONCLUSION: Several actors may support a return to work for individuals who received a disability pension due to musculoskeletal disorders. In order to succeed, however, it is essential that the disability pensioner is motivated for a reconstruction of his/her life. PMID- 17852267 TI - Pattern of disability among patients attending Taif Rehabilitation Center, Saudi Arabia. AB - PURPOSE: Despite the growing awareness of the community about the economic, psychological and medical impact of disability, limited research has been carried out to determine the pattern of disabilities in Saudi Arabia. METHODS: This is a cross-sectional study of hospital records of patients who were admitted to Armed Forces Rehabilitation Center, Taif, Saudi Arabia, during the period from 1999 2005. A total of 850 patient records were reviewed. Data were collected on age, sex, nationality, data of admission and discharge and type of disability. Univariate and multivariate logistic regression analyses were performed to determine predictors of long stay at the hospital. RESULTS: Trauma as an etiology of disability was more common than non-traumatic incidents among male and middle age patients (16-45 years). Traumatic accidents mostly result in quadriplegia (72.8%). Male, single, less than 45 years old, patients with traumatic accidents and patients with paralytic types of disability were significantly more likely to stay longer at the hospital (>or=6 months). CONCLUSIONS: The home care program should be expanded to minimize duration of stay at the rehabilitation centers with lower cost as well as health education of the public would help in encouraging disabled patients to adapt to daily life activities. PMID- 17852269 TI - Dysphagia in patients with Duchenne muscular dystrophy evaluated with a questionnaire and videofluorography. AB - PURPOSE: To investigate swallowing problems in patients with Duchenne muscular dystrophy (DMD) using a questionnaire and videofluorography (VF). METHOD: A questionnaire survey was performed of swallowing-related symptoms and VF in 31 male patients with DMD (mean age 19.9 years, range 9 - 26 years). The relationships among age, frequency of symptoms and VF abnormalities were analysed using Spearman's rank correlation. The differences in VF abnormalities among different food textures were analysed with the Kruskal - Wallis test. RESULTS: Symptoms related to pharyngeal phase dysfunction were more frequent than those related to oral and oesophageal phases. Coughing while eating was seen in 71% of the patients, choking while eating in 32% and the need to clear the throat in 26%. VF abnormalities were observed in 30 patients (96.8%). Common VF abnormalities included pooling in the valleculae (90.3%) and in the pyriform sinus (90.3%). Pharyngo-oral regurgitation was seen in 35.5% of the patients. Pooling in the pyriform sinus after repeated swallowing seen in VF correlated significantly with symptoms related to the pharyngeal phase (Spearman's rho 0.356 - 0.544). CONCLUSION: Because oropharyngeal dysphagia in DMD was evident in teenage patients as well as those without clinical symptoms, VF is recommended in patients with DMD. PMID- 17852272 TI - Immediate and long-term functional impact of repetitive locomotor training as an adjunct to conventional physiotherapy for non-ambulatory patients after stroke. AB - PURPOSE: The aim of the present study was to assess the heart rate intensity during gait training and to evaluate the relationship between heart rate intensity during gait training and walking ability of patients after stroke. METHODS: We included non-ambulatory patients within six weeks after first stroke. Over four weeks patients were trained five times a week, with either 20 minutes of repetitive locomotor training and 25 min of physiotherapy (RLT-PT), or 45 min of PT alone. We assessed the heart rate intensity during training period. Additionally we assessed walking ability (Functional Ambulation Categories) and the rate of independent ability to perform activities of daily life (Barthel Index) at the end of study and six months and three years later on. RESULTS: We included 30 patients in each group. Patients in RLT-PT group exercised longer in the HR target zone than in the PT group (16.1+/-11.8 min vs. 5.3+/-5.6 min, p<0.001). Higher heart rates were associated with independent walking at the end of study, at six months and at three years after the end of study (Fishers exact test, p=0.014, p=0.012 and p=0.017, respectively). CONCLUSIONS: Higher heart rate intensities during gait-training of non-ambulatory post-stroke patients may improve walking function. PMID- 17852273 TI - Rehabilitation psychology: meeting the needs of individuals with acquired disabilities in Ireland. AB - PURPOSE: The current articles reviews the epidemiology of disability in Ireland, discusses the political and social factors which have increased focus on disability issues and offers training guidelines for rehabilitation psychology based on those of the APA's Rehabilitation Psychology Division. RATIONALE: With the growing number of individuals with acquired (vs developmental) disabilities in Ireland, there is increased recognition of the need to train psychologists to assist persons with acquired disabilities (e.g. spinal cord injury, acquired brain injury, stroke, etc.) in adjusting to their impairments, reintegrating back into their communities and reducing the long-term financial costs associated with disability. CONCLUSION: Social and political factors suggest that the time is right to develop rehabilitation psychology as a specialty in Ireland given the increased focus on disability in Ireland, including recently passed disability legislation (i.e. 2005 Disability Bill), international events (e.g. 2003 Dublin World Special Olympics) and increases in rehabilitation training programmes (i.e. medicine; physio, occupational and speech therapy). PMID- 17852274 TI - Long-term outcome of superficialis-to-profundus tendon transfer in patients with clenched fist due to spastic hemiplegia. AB - BACKGROUND: Spastic hemiplegia is a common feature after stroke, which can result in a clenched fist deformity with secondary hygienic problems and pain. Operative treatment can improve these problems, although literature about its long-term effects is lacking. PURPOSE: To determine whether Superficialis-to-Profundus tendon (StP-) transfer procedure leads to permanent improvement of hygiene and reduction of pain in patients with clenched fist due to spastic hemiplegia following stroke. METHOD: Patients who underwent a StP-transfer in 2003-2005 were evaluated on skin condition, upper extremity joint mobility, resting position and muscle tone and with VAS scores on hygiene maintenance and pain in the hand. RESULTS: Six patients (mean age 54 years; duration after stroke 10 years) were included. Indications to operate were hygienic problems only (3) or combined with pain (3). The average follow-up period was 19 months. After 6 weeks of post operative splinting, no standard follow-up was applied. Serious post-operative complications were not reported. At follow-up no hygienic problems were present and pain was decreased in all except one patient. All hands could passively be fully opened. In resting position, flexion was seen in the MCP-joints (60-90 degrees). Muscle tone was raised in flexors of the wrist and fingers and m. adductor pollicis (Ashworth 1-2). Given the same pre- and post-operative circumstances, all patients would agree to have the surgery over again. CONCLUSION: Even 19 months after the StP-transfer for clenched fist, all operated hands could still be fully opened and there was a permanent improvement of hygiene and pain reduction. PMID- 17852275 TI - 'No going back' to institutional care for people with severe disability: reflections on practice through an interpretive study. AB - PURPOSE: This paper evaluated quality of life for people with a disability with high health and high support needs following a move from a congregate care institution to community housing. The study explored residents' perceptions of the service, level of community involvement, lifestyle choices, and input into decision-making. METHOD: An exploratory interpretative study was conducted using semi structured interviews with nine community house residents, ten community house staff and five family members. RESULTS: Participants were clear they definitely would not go back to the institution, but the relocation experience was not without difficulties. These issues related to 'site', 'staff' & 'skills'. CONCLUSIONS: Direct support staff hold considerable power to increase or diminish residents' quality of life. A targeted programme addressing specific site, staff & skill issues would strengthen quality of life for these very dependent residents. PMID- 17852276 TI - Participation in age-related activities and influence of cultural factors- comments from youth and parents of children with postnatal post infectious hemiplegia in Stockholm, Sweden. AB - PURPOSE: To investigate whether children with postnatal post-infectious hemiplegic cerebral palsy, and their parents, felt that participation in activities typical for the child's age and gender was affected. To identify factors, intra- and extra-personal that influenced disability with emphasis on factors related to immigration. METHOD: Interviews with six youths and 15 caregivers regarding the child's ability to participate in age-related activities, the consequences of disability in their home country compared to Sweden, and whether immigration influenced being a parent to a disabled child. RESULTS: All reported large difficulties participating in age-related activities. Positive and negative differences in participation in different cultures were described. War, culture, eating habits, hygiene habits, and school could differ and create difficulties when in Sweden. Language skills and intra personal factors influenced information gathering and participation in parental activities. CONCLUSIONS: Surprisingly large difficulties in participation may separate those with a postnatal post-infectious aetiology from hemiplegia of other aetiologies. High degrees of additional impairments may influence participation more than the physical disability. Language skills and cultural factors influence ability to seek and gain information. A mutual process where both Swedes and immigrants know traditions of care for disabled in both places may create understanding and improved dialogue. PMID- 17852277 TI - Developing a therapeutic relationship with a blind client with a severe intellectual disability and persistent challenging behaviour. AB - PURPOSE: A blind, severely intellectually impaired boy aged 17 with Down syndrome and persistent serious challenging behavior received attachment-based behavior modification treatment. The aim was to study the effect of the treatment and the development of the therapeutic attachment relationship. METHOD: In a single-case study, attachment therapy sessions alternated with control sessions. Treatment started with attachment therapy (phase 1), followed by behavior modification (phase 2). The instruments used were: Residential observation lists for challenging behavior, video analyses of attachment behavior in therapy sessions and physiological indicators of affect regulation measuring the pre-ejection period (PEP) and respiratory sinus arrhythmia (RSA) as indices of cardiac sympatho-vagal activity. RESULTS: The client exhibited less frequent and less intensely challenging behavior. The data indicated more appropriate replacement behavior and less PEP arousal during the behavior modification treatment given by the attachment therapist compared to the control therapist who used the same protocol. The client showed more active and longer-lasting attachment behavior, especially proximity seeking, towards the attachment therapist than towards the control therapist. CONCLUSIONS: Attachment-based psychotherapy proved successful in eliciting attachment behavior in a severely intellectually disabled, socially deprived, behaviorally and affectively dysregulated adolescent. The resulting relationship proved to be a therapeutic platform conducive to behavior change. PMID- 17852278 TI - Assessment of GPs' beliefs relating to the care of people with intellectual disabilities: a Taiwan-based, opportunity-guided approach. AB - PURPOSE: This study was designed to investigate general practitioners' (GPs) beliefs about the perceived importance of their role in, and their satisfaction with, providing healthcare to people with intellectual disabilities. The identification of healthcare issues with potential for improvement was assessed using gap analysis and an opportunity-guided method. METHOD: A cross-sectional census survey by a mail-structured questionnaire recruited 331 GPs (response rate -16%) who provided information on healthcare for people with intellectual disabilities in 2006 in Taiwan. RESULTS: The results indicated that GPs considered their role in providing healthcare for people with intellectual disabilities to be important (mean score 7.2-8.3). However, the respondents generally did not feel satisfied (mean score 4.6-5.5) with their achievements in treating patients with intellectual disabilities. We found that the gender and educational level of the respondents were statistically correlated to the perceived importance they considered their work to have, while the factors of age, medical practice setting and training experience in intellectual disability were statistically correlated to GPs' perceived satisfaction in providing healthcare to people with intellectual disabilities (p < 0.05). Those healthcare issues of'training and experience in intellectual disability', 'multi disciplinary and multi-sectoral cooperation', 'adequate competence in disability diagnosis', 'genetic consulting services', 'duty of disease prevention and health promotion', and 'adequate medical consultation time' were the five most promising areas to be improved in healthcare for people with intellectual disabilities according to the opportunity-guided analysis. CONCLUSIONS: This study highlights that health professionals need to examine carefully healthcare issues pertaining to people with ID, and that much more effort is required to develop appropriate healthcare policies based on the opportunity-guided health issues identified here. PMID- 17852280 TI - Interface pressure measurements: visual interpretation of pressure maps with MS clients. AB - PURPOSE: Pressure mapping systems provide useful information for pressure care assessment. Healthcare professionals tend to rely upon their colour-coded pressure maps to assist clinical decision-making, based on ranking these from best to worst pressure distribution. The current study investigated whether such ranking is an appropriate method of assessment when compared to use of the numerical output of average and maximum pressure values (mmHg), yielded by the system. METHOD: This community-based correlational study involved 27 multiple sclerosis clients (15 wheelchair users; 12 non-wheelchair users). Pressure maps were recorded on each participant's current seating surface and on six pressure reducing cushions, using the Force Sensing Array pressure mapping system. Outcome measures included (1) rank order of pressure maps based on visual interpretation by two occupational therapists, (2) average pressure (mmHg) and (3) maximum pressure (mmHg). Visual ranking of the colour-coded pressure maps was correlated with average and maximum pressure values for each map. RESULTS: Correlations between visual ranking of maps and maximum pressures were high for six out of seven surfaces (p < 0.05) for non-wheelchair users; however, they were much less between average pressures and visual interpretation for the same cohort. Similarly, correlations between visual ranking of maps and average pressures for wheelchair users was minimal and was only noted as being high (p < 0.05) on two surfaces when considering maximum pressures and visual interpretation. CONCLUSIONS: This study contests the usefulness of the visual ranking of pressure maps in interpreting interface pressures with MS clients, especially with wheelchair users. Visual interpretation of pressure maps by clinicians may be useful in eliminating inappropriate support surfaces from a selection, or those that display easily identifiable 'extremes' of pressure values. Clinicians need to incorporate and interpret the numerical data as well as pressure maps when conducting their assessment and making provision. PMID- 17852281 TI - Clinometric properties of a clinical spasticity measurement tool. AB - PURPOSE: To investigate clinometric properties of an Anglo-Dutch spasticity measurement tool (ADSMT), an objective tool providing information about both neurophysiological and biomechanical aspects of spasticity about the wrist joint in the clinical setting. METHOD: ADSMT measurements were performed with 12 healthy and 11 participants with post-stroke spasticity, and consisted of assessing the maximum range of passive wrist movement (pROM) and passive wrist extension at different cycle rates. Outcome measures were wrist angle, flexor and extensor activation, and resistance to movement. Intra-class Correlation Coefficients (ICCs) were calculated for inter-rater and test-retest reliability. Validity was investigated by calculating Spearman's rho between ADSMT outcome measures and the Modified Ashworth Scale (n=12), the Action Research Arm Test (n=6), and a validated wrist rig (n=6). RESULTS: Impaired participants had higher flexor activity and higher resistance to movement during passive wrist extension compared to unimpaired participants. For all outcome measures inter-rater and test-retest reliability were satisfactory to good and concurrent validity was sufficient. CONCLUSIONS: Outcome measures related to wrist flexor activity and resistance to movement during extension are promising for spasticity assessment using the ADSMT. Further knowledge on reference values and practicality is necessary for this tool to become incorporated in the clinical setting. PMID- 17852282 TI - Prediction of hand function after occupational hand injury by evaluation of initial anatomical severity. AB - PURPOSE: To examine the relationship between initial anatomic severity evaluated by the Hand Injury Severity Scoring (HISS) system and recovered hand function evaluated by the Purdue Pegboard after occupational hand injury. METHOD: In the retrospective cohort study, 95 patients hospitalized between 1 January 2000 and 31 December 2003 for surgery due to occupational hand injury were recruited. The HISS scores were obtained by chart review by a surgeon. The Purdue Pegboard was performed at least 6 months after the injury by well-trained occupational therapists. The Purdue Pegboard scores were compared with the initial HISS scores by simple regression, multiple regression and logistic regression analysis. RESULTS: The total HISS score was negatively correlated with scores of the Purdue Pegboard subtests, including injured-hand, both-hands, and assembly. The risk of having low injured-hand score (<13) was significantly increased in workers with initial major severity (HISS >or= 101), with OR 9.57 (95% CI 1.4-94.8). The risk of having low both-hands score (<10) was significantly increased in workers with initial severe and major severity (HISS of 51-100 and >or=101), with OR 4.5 (95% CI 1.1-21.8) and OR 25 (95% CI 3.5-263). The risk of having low assembly score (<25) was significantly increased in workers with initial major severity (HISS >or= 101), with OR 9.0 (95% CI 1.3-72.5). CONCLUSION: The study showed that after occupational hand injury, initial anatomic severity evaluated by the HISS system could predict hand function after recovery. PMID- 17852283 TI - Understanding the role of sex differences in work injuries: implications for primary care practice. AB - PURPOSE: Primary care physicians care for work-injured women and men, yet there is little information on sex differences in outcomes and factors contributing to post-injury outcomes to guide their evaluation and recommendations. METHODS: Two self-administered questionnaires were sent to a large sample of women and men with work injuries reported to the New Hampshire (USA) Department of Labour between November 2000 and March 2002. Factors associated with the work injury and outcomes were assessed. RESULTS: A total of 3001 persons (1448 women and 1553 men) completed the first questionnaire and 67% completed the second questionnaire. Work-injured women were significantly younger, more educated, more likely to be single, had more pre-injury comorbidities, and worked in less physically demanding occupations as compared to work-injured men. Women's injuries were more often a result of routine job tasks and of gradual onset. Women had worse long-term outcomes including job stability and post-injury income. In multivariate analyses, being female was independently associated with a negative employer response and greater future work concerns. CONCLUSIONS: Women and men differ in terms of work injury circumstances and factors contributing to post-injury outcomes. Primary care providers should consider sex when evaluating and treating work-injured adults. PMID- 17852284 TI - The Everyday Memory Questionnaire-revised: development of a 13-item scale. AB - PURPOSE: The Everyday Memory Questionnaire (EMQ) was developed as a subjective measure of memory failure in everyday life. Previous studies have investigated the factor structure of the EMQ in both healthy participants and people with multiple sclerosis (MS). The aim of the present study was to confirm the factor structure of the EMQ, to determine the internal consistency and criterion validity of the scale and to develop a shortened version. METHOD: A retrospective design, including participants from a study on MS patients and their carers and a study on stroke patients. Psychometric properties of the EMQ-28 were explored, and the measure was further revised from comparative analyses between the clinical and non-clinical groups. RESULTS: Reliability and factor analysis of the EMQ-28 identified two main factors, general memory and attentional function, showing some concordance with previous research. Further analysis reduced the questionnaire to a 13-item measure (EMQ-R), with two main factors (Retrieval and Attentional tracking), strong internal reliability, and good discriminatory properties between clinical and control groups. CONCLUSIONS: The 28-item questionnaire consistently differentiated between two broad systems of memory and attention, with some differentiation of visual and verbal, or language systems. Results showed some consistency with previous findings. The revised, 13-item questionnaire is a valid and reliable tool that has good face validity for use with neurological patients. Further exploration of the revised EMQ is recommended to provide information regarding its psychometric and clinical properties. PMID- 17852285 TI - Development of a framework for the evidence-based choice of outcome measures in neurological physiotherapy. AB - BACKGROUND: Neurological physiotherapists recognize the need to include standardized outcome measures (OMs) in clinical practice but lack of information about the OMs available hampers utilization. This paper reports on the first stage of a project to identify the most robust OMs for use in neurological physiotherapy. OBJECTIVE: To identify what physiotherapists perceive that they need to measure during a neurological assessment. METHODS: Three separate workshops were held using patient vignettes to represent the acute, rehabilitation and community settings. Thirty senior neurological physiotherapists participated and were asked: 'What would you observe, test or measure if assessing this patient?' Data were analysed using thematic content analysis performed independently by each of the authors. Internal and external member checking ensured validity. In addition, the authors produced definitions of the items and domains identified in the data collection and subsequent content analysis. RESULTS: Items from the data collection were classified into 16 domains that physiotherapists need to measure: Weakness; range of movement/contracture; pain; muscle tone/spasticity; sensation; ataxia/co-ordination; personal fatigue; oedema; subluxation; postural and balance impairment; walking impairment; upper limb; balance disability; walking disability; mobility disability and falls. CONCLUSIONS: The domains that physiotherapists need to measure during clinical assessment were identified. In the second stage of the project these domains will inform systematic reviews to identify the most robust outcome measures for use in clinical practice. PMID- 17852286 TI - Reliability of four scales on balance disorders in persons with multiple sclerosis. AB - PURPOSE: Balance rehabilitation is an important component of the retraining program in people with multiple sclerosis (MS). Measuring balance is fundamental for an accurate assessment and therapy selection. The aim of this study was to compare interrater and test-retest reliability of the Berg Balance Scale, the Dynamic Gait Index, the Dizziness Handicap Inventory and the Activities-specific Balance Confidence. METHOD: A group of 25 persons were enrolled in the study. The group consisted of 8 males and 17 females, mean age 41.7 years (12.5 years, SD). The onset of pathology was 8.7 years (8.8 years SD) before the beginning of the study. To assess the test-retest reliability two consecutive assessments were collected by the same rater. To assess the inter-rater reliability persons were concurrently assessed by two raters. RESULTS: The Intraclass Correlation Coefficients (ICCs) for interrater reliability ranged between 0.94 and 0.96. The ICCs for test-retest reliability ranged between 0.85 and 0.96. CONCLUSION: The inter-rater reliability of the instruments proved to be satisfactory. Lower but acceptable results were obtained for the test-retest paradigm. The data obtained in this study suggest that these scales are reliable tools for assessing balance function in persons suffering from MS. PMID- 17852287 TI - Disseminating the WHO International Classification of Functioning Health and Disability (ICF) in the Veneto region of Italy. AB - PURPOSE: To show the feasibility and effect of a large formation effort focused on the International Classification of Functioning, Disability and Health (ICF), which may introduce a revolutionary new conceptual framework for people involved in rehabilitation services. METHODS: We here describe the large information/formation project launched by the Regional Direction for Social Services of the Veneto region (Italy). Here we describe the first of the two steps of the project, aimed to reach 900 health professionals throughout the whole region. They were exposed to a structured modular course consisting of a mix of frontal lectures and workshop sessions. During the workshop sessions the participants were confronted with questions referring to the actual application of ICF in their services. RESULTS: The results show that the attendance (90%) was very high. The workshop sessions provided interesting indications on the possible applications of ICF in the clinical settings, as well as points of strength and potential problems that the implementation of ICF may have in the Regional Health Service. CONCLUSIONS: To our knowledge this is the largest alphabetization effort on ICF attempted in a public health system, and it indicates a possible effective approach to its controlled diffusion and future implementation. PMID- 17852288 TI - Operationalizing community participation in community-based rehabilitation: exploring the factors. AB - PURPOSE: The purpose of this article is to critically discuss issues that pertain to the operationalization of community participation in community-based rehabilitation (CBR). METHOD: Data were drawn from an international, questionnaire-based survey of occupational therapists involved in CBR conducted through the World Federation of Occupational Therapists. A search of CINAHL. PsychInfo and Medline databases for articles on CBR was performed and both descriptive articles and analytical ones were included. RESULTS: Although there are guidelines on the nature of CBR these do not always match its application in practice. Active involvement of local communities in CBR projects is often limited, threatening the sustainability of CBR programmes. Furthermore, the failure to acknowledge the sociopolitical underpinnings and the cultural nature of disability is likely to compromise the nature of disabled people's involvement in CBR. CONCLUSIONS: There is confusion and lack of clarity about the nature of CBR. Educational modules on CBR should be made available to professionals. These should consider the importance of community involvement and context-specific and culture-sensitive programmes in practice. PMID- 17852289 TI - Self-reported hearing difficulties, communication strategies and psychological general well-being (quality of life) in patients with acquired hearing impairment. AB - PURPOSE: The aims were to (i) translate the Amsterdam Inventory for Auditory Disability and Handicap (AIADH) into Swedish and evalute its usefulness, (ii) describe hearing difficulties and psychological well-being (quality of life) and (iii) explore variables related to psychological well-being in a Swedish population. METHOD: Seventy-nine consecutive patients, referred to the hearing clinic for hearing examination and audiological rehabilitation, formed the study sample. Along with pure-tone audiometry, the AIADH, the Psychological General Well-being index and the Communication Strategies Scale were used. RESULTS: Men had significantly worse hearing on the high frequencies (2, 3, 4 and 6 kHz) than women but their quality of life was significantly higher than for women. Men scored significantly lower on 'auditory localization' and adopted non-verbal communication strategies less often than women. A stepwise regression analysis showed that 'maladaptive behaviours' and 'intelligibility in quiet' explained 48% of the variance in quality of life. CONCLUSION: Psychosocial consequences of hearing loss, such as lowered quality of life, cannot be predicted from audiometric data alone. The adverse relationship between maladaptive behaviour and quality of life emphasizes the relevance of developing training programs aiming to improve coping with the consequences of a hearing impairment. The AIADH may be useful in assessing self-reported difficulties among patients with hearing problems, but needs to be further developed in terms of psychometric evaluations and reliability testings based on a larger representative sample. PMID- 17852291 TI - The impact of psychological factors in recovery following surgery for hip fracture. AB - PURPOSE: To increase awareness of psychological factors in recovery from hip fracture and to describe strategies that can be used to help patients in the process of recovery. METHOD AND RESULTS: Psychological theory, case examples and clinical observation are used to propose three frameworks for understanding the psychological factors which can impede recovery. Indication of key strategies for assessment and intervention which can be used in rehabilitation services is provided. CONCLUSIONS: An understanding of the psychological factors which can impede recovery in hip fracture is important for all professionals involved in rehabilitation. Psychologists can provide consultation and support for staff working in physical rehabilitation and can work directly with cases where there is complexity. There is still relatively little known about this important area and further research is needed to provide a clear evidence base. PMID- 17852292 TI - The effect of Qigong on fibromyalgia (FMS): a controlled randomized study. AB - PURPOSE: To evaluate the effect of a 7-week Qigong intervention on subjects with Fibromyalgia Syndrome (FMS). METHODS: The study was a controlled randomized study with repeated measures. Fifty-seven FMS female subjects were randomly assigned to an intervention group (n = 29) or a waiting-list control group (n = 28). After completion of the experimental part, the control group received the same intervention. Collection of data was made at pre- and post-treatment and at 4 month follow-up for both groups. RESULTS: During the experimental part of the study, significant improvements were found for the intervention group, at posttreatment, regarding different aspects of pain and psychological health and distress. Almost identical results were found for the combined group. At 4-month follow-up, the majority of these results were either maintained or improved. CONCLUSION: The overall results show that Qigong has positive and reliable effects regarding FMS. A high degree of completion, 93%, and contentment with the intervention further support the potential of the treatment. The results of the study are encouraging and suggest that Qigong intervention could be a useful complement to medical treatment for subjects with FMS. PMID- 17852293 TI - Effects of transcutaneous electrical stimulation combined with locomotion-like movement in the treatment of post-stroke gait disorder: a single-case study. Short report. AB - PURPOSE: This study was designed to examine the effects of electrical stimulation combined with locomotion-like movement (ES/LM) for improving gait disorder in a stroke patient. METHOD: A four-phase ABAB single-subject design with five therapy sessions per phase was employed. In the intervention phases, transcutaneous electrical stimulation was applied to the tibialis anterior (at the end of the hip extension phase and in the initial hip flexion phase) and the soleus (in the initial hip extension phase) during passive hip flexion and extension. To assess improvement, the soleus H-reflex and the ambulatory function were measured (gait velocity and step length). RESULTS: Application of ES/LM resulted in a decrease of the soleus H-reflex and significant increase of gait velocity and step length. CONCLUSION: These findings suggest that ES/LM is a feasible treatment method for impaired ambulatory function in stroke patients at the subacute stage after the event. PMID- 17852294 TI - Development of a measure of functioning for stroke recovery: the functional recovery measure. AB - PURPOSE: To develop a parsimonious measure of functioning for persons after stroke. METHOD: A sub-set of 206 community-dwelling subjects with a first stroke from a larger cohort was interviewed within 9 months using 39 items from five indices assessing functioning. Information was collected on influencing variables: age, stroke type and severity, and previous health. Two statistical methods, factor analysis and Rasch analysis, confirmed the item structure, hierarchy and dimensionality of the measure. Statistics confirmed fit to the model; internal consistency was also assessed. Items were deleted iteratively based on fit and relationship to the construct. RESULTS: The subjects were predominately male (63%) aged on average 68-years-old. A 12-item unidimensional functioning measure was developed. All items and persons fit the Rasch model with stable item-person reliability indices of 0.98 and 0.91, respectively. Item precision (standard errors) ranged from 0.14-0.37 logits. Gaps in measurement occurred at the extremes of the measure and there was a small ceiling effect. CONCLUSIONS: A 12-item measure captured the concept of functioning that could be used as a prototype to quantify recovery post-stroke. These items could form the basis for a measure of functioning. PMID- 17852295 TI - Intrathecal phenol: an old treatment revisited. AB - PURPOSE: Severe bilateral leg spasticity can cause severe symptoms and reduced quality of life in affected individuals. It is often unresponsive to treatment. The objective of this study was to review the effectiveness of intrathecal phenol in the treatment of severe bilateral leg spasticity. METHOD: A retrospective case notes review of patients treated with intrathecal phenol by a rehabilitation service was performed. A simple rating scale based on comments in the case notes was used to identify changes in spasticity and treatment goals. RESULTS: Forty patients were identified as having been treated with intrathecal phenol over a 10 year period. All patients had improvements in their spasticity, 34 of which were rated as substantial or excellent. All patients (in whom the effect was documented), except one, had short-term improvement in the goals for treatment, 31 having substantial or excellent improvement. The effect was long lasting in many of the patients. Seven patients required repeat injections with similar outcomes. Seven patients experienced temporary side-effects. CONCLUSION: Intrathecal phenol is a useful alternative in treating selected patients with chronic severe bilateral leg spasticity that is unresponsive to other treatments. PMID- 17852296 TI - Manual dexterity and related functional limitations in hereditary motor and sensory neuropathy. An explorative study. AB - PURPOSE: To explore impairments in manual dexterity and perceived limitations in upper extremity-related activities in subjects with Hereditary Motor and Sensory Neuropathy (HMSN). METHOD: Cross-sectional study of 20 HMSN subjects. Manual dexterity was assessed using the Jebsen test of hand function. Perceived limitations were assessed using the Rehabilitation Activities Profile (RAP) and the Disabilities of Arm, Shoulder and Hand questionnaire (DASH). RESULTS: Impaired manual dexterity was found in four out of seven Jebsen sub-tests. Turning over cards, lifting large light and large heavy objects were most impaired, as reflected by median z scores of 5.7, 12.0 and 16.9, respectively. Perceived limitations, as reflected by median and percentile (P25; P75) sum scores, were 7.5 (3; 11.7) for the RAP domains of personal care (scale 0-69) and 6.0 (1.25; 15.5) for the domains of occupation (scale 0-42). The median (P25; P75) DASH score (scale 0-100) was 13.3 (2.7; 48.1). Jebsen test scores were significantly associated with RAP and DASH scores. CONCLUSIONS: Manual dexterity of HMSN subjects, especially requiring the manipulation of flat and of large objects, was impaired and associated with the amount of perceived limitations in upper extremity function. Major limitations were perceived in activities related to upper extremity function by 25% of HMSN subjects. Measurement of manual dexterity and perceived limitations should be incorporated into the evaluation and treatment of HMSN subjects. PMID- 17852297 TI - Assessment of fatigue in patients with fibromyalgia and chronic widespread pain. Reliability and validity of the Swedish version of the MFI-20. AB - OBJECTIVES: Fibromyalgia (FM) and Chronic Widespread Pain (CWP) are common diseases in primary care and, in addition to the pain they cause, fatigue is a major problem. Fatigue is regarded as a multidimensional concept and instruments assessing fatigue should therefore cover several different dimensions. The Multidimensional Fatigue Inventory (MFI-20) measures five different dimensions of fatigue. The aim of the study was to investigate the test-retest reliability and convergent construct validity of the Swedish version of the MFI-20 in female patients with FM or CWP. METHODS: To investigate the convergent construct validity, 166 female patients with FM or CWP completed the Swedish version of the MFI-20 and a Visual Analogue Scale (VAS) measuring global fatigue. Thirty-six of the 166 patients completed the Swedish version of the MFI-20 on two occasions, one day apart to evaluate the test-retest reliability. RESULTS: Spearman's correlation coefficient revealed a significant association between each of the five subscales of the MFI-20 and the VAS for global fatigue. General Fatigue had the highest correlation with the VAS (rs = 0.62, p < 0.001), while Reduced Motivation had the lowest (rs = 0.32, p <0.001). The intra-class correlation coefficients (ICC) were satisfactory for all the five subscales of the MFI-20. CONCLUSION: The results of this study indicate that the Swedish version of the MFI-20 is a reliable tool for assessing the degree of fatigue in patients with FM or CWP. This study also supports the theory that fatigue is a multidimensional concept and different aspects of fatigue should be measured separately. PMID- 17852298 TI - Back to work--evaluation of a multidisciplinary rehabilitation programme with emphasis on musculoskeletal disorders. A two-year follow-up. AB - PURPOSE: The aim of this study was to evaluate the 2-year outcome of a multidisciplinary rehabilitation programme for working-age people, regarding sick leave and mental health. METHOD: The test persons consisted of 40 women and 20 men (mean age 46.8 +/- SD 7.9) with musculoskeletal disorders, mainly neck and back pain. The rehabilitation programme was individually adapted and consisted of physical activity in several forms, relaxation, theoretical and practical education and individual guidance. Before, during and after the programme all participants were evaluated with the Global Self-Efficacy Index, Hospital Anxiety and Depression Scale, and stress test. RESULTS: At the 2-year follow-up full-time sick leave had decreased by 37% (p < 0.0001) in the women, and by 25% (p < 0.05) in the men. Both women and men showed an increased quality of life (QoL) and decreased anxiety, depression and self-experienced stress at the 2-year follow-up compared with the start of the rehabilitation programme. CONCLUSIONS: The most important conclusion was that the effects of the rehabilitation programme persisted for up to 2 years. At 2 years the majority of the participants were still physically active, their QoL was increased, and most participants had returned to work. PMID- 17852299 TI - Relationship between executive functions and productivity outcomes following stroke. AB - PURPOSE: Stroke occurs in many individuals of working age and can considerably disrupt their capacity for employment and other productive activities. Few studies have examined the relationship between loss of productivity and cognitive impairment, particularly deficits in executive function. The present study examined whether performance on tests of executive function is related to employment and productivity at 12-months follow-up. METHOD: Twenty-seven individuals (mean age = 47.3 years, SD = 10.7) on average 2.1 years (SD = 1.6) post-stroke were recruited from hospital and community rehabilitation services and administered a theory-driven battery of executive function tests (i.e. Health and Safety sub-test, FAS Test, Five-Point test, Key Search Test and Tinkertoy Test). A 12-month follow-up assessment of employment outcome ('employed' or 'unemployed') and productivity (measured by the Sydney Psychosocial Reintegration Scale) was conducted. RESULTS: A series of between-group comparisons identified that a measure of purposive behaviour and self-regulation (i.e. the Tinkertoy Test) best distinguished between the employed and unemployed groups (p < 0.01) irrespective of time since injury and neglect. Level of post-stroke productivity was significantly correlated with measures of planning (p < 0.05), self monitoring (p < 0.01) and self-regulation (p < 0.05), as well as time since injury (p < 0.05) and functional status (p < 0.01). CONCLUSIONS: These findings highlight the importance of routinely assessing executive functions to guide cognitive rehabilitation interventions following stroke. PMID- 17852300 TI - 'It was hard but you did it': the co-production of 'work' in a clinical setting among spinal cord injured adults and their physical therapists. AB - PURPOSE: This paper focuses on what takes place during the rehabilitation of spinal cord injured (SCI) adults. It analyses the cardinal rehabilitation task of transforming the compromised, limited and injured corporeal style of newly injured adults (best described phenomenologically as an 'I cannot do' or 'I no longer can') into a new style of embodiment, one in which 'I am newly abled'. This transformation is not a passive, surrendering experience. Rather, as informants repeatedly noted, 'rehabilitation is hard work'. This paper examines that 'work'. METHOD: This paper draws from observational and interview data collected over an 18-month period in a metropolitan rehabilitation centre in the Midwestern United States. It presents an exemplar case of a clinical setting, that between a physical therapist and her SCI client. RESULTS: The interactional and meaning-making nature of clinical encounters are explicated, revealing the collaborative and situational constitution of rehabilitation work. CONCLUSIONS: Experience-near, phenomenologically informed, research is shown to be a valuable way of understanding rehabilitation practices and how they might affect inpatients and staff. PMID- 17852301 TI - User satisfaction with mobility assistive devices: an important element in the rehabilitation process. AB - BACKGROUND: An assistive device often means an evident change in a person's ability, more easy to notice than the effects of most of other types of physiotherapy or occupational therapy intervention. In spite of this, there is very little evidence in this area. PURPOSE: The objective was to follow-up user satisfaction with and the use and usefulness of rollators and manual wheelchairs. The objective was also to determine any difference in satisfaction between users of the two different types of mobility assistive products. METHODS: A random sample of 262 users participated in the study, 175 rollator users and 87 wheelchair users. The Quebec User Evaluation of Satisfaction with Assistive Technology-QUEST 2.0 and an additional questionnaire were used for data collection. RESULTS: Overall satisfaction with both types of device was high and most clients reported use of their device on a daily basis. There was a difference in how the users estimated the usefulness and other characteristics as well as some service aspects related to prescription and use of the two types of device. Most users reported not having had any follow-up; however, most users had not experienced any need for one. CONCLUSIONS: A standardized follow-up will give rehabilitation professionals continuous and valuable information about the effect of and satisfaction with assistive devices. PMID- 17852302 TI - What do referred patients with upper extremity musculoskeletal disorders expect of a multidisciplinary treatment and what is the perceived value? AB - PURPOSE: To describe reasons for not starting and to determine expectations and perceived value of multidisciplinary treatment among referred patients, sick listed due to upper extremity musculoskeletal disorders METHOD: Twenty-six randomly chosen referred patients who did not start the treatment were interviewed by telephone to identify their reasons for not starting and 24 randomly chosen patients who participated in the treatment were interviewed face to-face to explore their expectations and experiences of multidisciplinary treatment. RESULTS: Reasons for not starting the treatment are mainly intrinsic to the treatment. The most important reason was that the treatment was thought to be too psychological in nature. Most treated patients had no prior expectations but saw it as a last resort for their complaints. The psychological (cognitive behavioural) component was perceived as the most useful part that acquired the ability to cope with their complaints and developed an increased self-awareness. Most treated patients are satisfied, although some said the treatment did not meet their expectations, because their complaints had not disappeared. CONCLUSION: The most important reason for not starting the treatment was the assumption that the treatment is too psychological in nature, while in treated patients the psychological sessions were perceived as most useful treatment component. PMID- 17852303 TI - No advantages of Gamma nail over sliding hip screw in the management of peritrochanteric hip fractures: a meta-analysis of randomized controlled trials. AB - PURPOSE: There is a lack of consensus regarding the best option for the operative treatment of peritrochanteric fractures. A meta-analysis was performed to assess the surgical outcomes of peritrochanteric fractures. METHODS: Only prospective, randomized studies comparing Gamma nail and sliding hip screw (SHS) fixation in adults were included. Eleven studies met the inclusion criteria: the target population consisted of patients with peritrochanteric fractures, while subtrochanteric fractures were not included; the intervention was SHS compared with Gamma nail; the study was a published randomized trial. Each outcome measure tested was assessed for heterogeneity. If significant heterogeneity was present, data from the studies were not combined. If there was no significant heterogeneity, a combined relative risk was calculated using a fixed effects model and a Z-test was performed to test the overall effect. RESULTS: A total of 1344 peritrochanteric fractures entered into the included studies. There were no differences of mortality, cut-out, non-union, re-operation, wound infection, intra-operative fractures of femur, blood loss or surgical time. CONCLUSIONS: It seemed that there were no obvious advantages of Gamma nail fixation over SHS fixation in treating peritrochanteric fractures. PMID- 17852304 TI - Evaluation of gross motor abilities and self perception in children with amblyopia. AB - PURPOSE: The present study evaluates gross motor abilities and self perception about the physical abilities of pre-school children with amblyopia, in comparison to their unaffected peers. METHOD: Twenty-two children with amblyopia, and 25 children with normal vision, aged 4-7, were included in this study. Gross motor abilities were evaluated by the Movement Assessment Battery for Children (MABC). The Pictorial Scale of Perceived Competence and Social Acceptance for Young Children were used to measure physical self perception. Parents completed a questionnaire about everyday situations revolving around the child's balance and posture abilities. RESULTS: Amblyopic children performed significantly worse than the controls according to the MABC subtests and the parents' questionnaire total score. In the scale of perceived competence evaluation the amblyopic children had lower scores in half of the items as well as in the total mean score, but the differences between the groups were not significant. Among the study group, significant correlations were found between several items in the parents' questionnaire and the children's' mean balance score in MABC. CONCLUSIONS: Amblyopia may negatively impact children's motor abilities as expressed by the objective measures in daily living, while self perception is less affected. PMID- 17852305 TI - The use of classification models in the evaluation of CBR programmes. AB - Classification models for community-based rehabilitation (CBR) create conceptual order in the many types of rehabilitation programmes that exist in developing countries. Several models have been developed but none of the models appears to be widely accepted or being used in the evaluation process. PURPOSE: To review classification models and assess its usability. METHODS: Literature review. RESULTS: Sixteen documents were found describing 11 different models. These models vary from simply listing different types of CBR to multidimensional configurations encircling principles, methods and outcomes of CBR. The models are only incidentally used in the evaluation of CBR programmes. The more recent models have been used to develop, select and group indicators. CONCLUSIONS: Classification models can indeed structure the evaluation and comparison of CBR programs that are, by nature, very different from each other. Indicators can be developed within a theoretical framework provided by the classification model. In order to be widely accepted the models should be made less complex and focus on outcomes that are meaningful for the people involved in the evaluation as well as for policymakers and researchers. PMID- 17852306 TI - Factors associated with health-related quality of life in patients with severe Guillain-Barre syndrome. AB - PURPOSE: To compare the health-related quality of life (HRQOL) in control subjects and patients with severe Guillain-Barre syndrome (GBS) 6 months after rehabilitation. To determine the relationship of several sociodemographic and medical factors with the HRQOL of the GBS survivors. METHODS: Thirty-one patients with severe GBS and 31 control subjects were included in the study. Demographic and medical variables were recorded. The functional outcome was measured using the Functional Independence Measure (FIM), both at admission and discharge and also at the 6-month follow-up examination. The HRQOLs were assessed by the Nottingham Health Profile (NHP) at the 6-month follow-up examination. RESULTS: There were significant improvements in functional status as measured by the FIM at discharge and also at 6 months. The scores of all of the NHP dimensions of the GBS patients were significantly higher than in the control subjects. Functional disability scores were highly related to the energy level, physical mobility and emotional reactions of the NHP domains. Education, gender, employment, mechanical ventilation and tendency to depression were the factors most related to the NHP domains. Age and marital status showed no significant correlation with the NHP scores. CONCLUSION: The HRQOL of the GBS patients remains lower than that of the control subjects. In addition to functional scores, several sociodemographic and medical variables, such as education, psychological factors, gender, mechanical ventilation and employment may play a crucial role in determining the quality of life in persons with GBS. PMID- 17852307 TI - Is part-time work a good or bad opportunity for people with disabilities? A European analysis. AB - PURPOSE: The purpose of this article is to analyse the incidence of part-time employment among people with disabilities within a European context. Particular attention is paid to the type of part-time employment (voluntary vs. involuntary) and the levels of job satisfaction that people with disabilities report. METHOD: Using data from the European Community Household Panel for the period 1995-2001, we estimate part-time rates, preferences and levels of job satisfaction for people with and without disabilities for 13 European countries. RESULTS: The results show that a higher number of people with disabilities work part-time, compared to non-disabled workers. This is mainly due to disabled part-time workers having a much higher preference for part-time working than people without disability. This finding is corroborated when we analyse the levels of job satisfaction for disabled part-time workers. CONCLUSIONS: Part-time employment becomes a relevant instrument for policy makers and employers to improve the social inclusion, income and labour conditions of the people with disabilities because it allows these people to achieve a much better balance between their personal and health needs and working life. PMID- 17852308 TI - Intrathecal Baclofen: a discussion on impact that medical advances can have on the individual and the implications this has for a society that is built on an ethic of social medicine. AB - PURPOSE: The intention of this article is to examine the impact of medical advances and new medical technologies on the lives of individuals with disabilities and chronic illness. It looks at the problem of balancing social expectation, cost and individuals quality of life. METHOD: A personal case study that looks at the use of Intrathecal Baclofen to relieve the spasticity related to cerebral palsy; improving personal function and enhancing quality of life. CONCLUSIONS: Advances in medical technology such as Intrathecal Baclofen can undoubtedly greatly enhance quality of life. We live in a society that has heath provision at its heart and an expectation that all needs will be met. With ever more costly treatments, will it ultimately prove to be need or cost that will define health treatment in the future? PMID- 17852309 TI - Cognitive-behavioural stimulation protocol for severely brain-damaged patients in the post-acute stage in developmental age. AB - PURPOSE: To present a cognitive-behavioural stimulation (CBS) protocol designed to help severely damaged patients in the early post-acute stage by describing the underlying methodology and assessing its efficacy compared to traditional rehabilitation methods. This protocol combines multisensory stimulation and cognitive-behavioural techniques to elicit and intensify the occurrence of adaptive responses and reduce maladaptive behavioural patterns. METHODS: A control group and an experimental group--both evaluated with the Levels of Cognitive Functioning Assessment Scale (LOCFAS)--were compared at the beginning of the rehabilitation programme and at the end of it. The control group consisting of patients assessed and treated before receiving the CBS protocol was enrolled in a traditional rehabilitation programme (only physical therapy and speech therapy). Besides the traditional therapy, the experimental group also received the CBS protocol. RESULTS: Patients on the CBS protocol show a greater improvement and are therefore more responsive than the control group after the 16 week remediation programme. The mean LOCFAS improvement of the experimental group is more marked during the first month of rehabilitation and is associated to the entry LOCFAS level, while in the control group the improvement on LOCFAS is considered to be 'spontaneous' and is associated to the aetiology of the brain damage. CONCLUSIONS: Our results show a better initial outcome for patients receiving the CBS protocol. PMID- 17852310 TI - Physiotherapy in Afghanistan--needs and challenges for development. AB - PURPOSE: The aim of this paper is to describe and analyse the current situation of the physiotherapy component of the Rehabilitation of Afghans with Disability (RAD) programme, in order to identify the needs and challenges for further development. METHOD: The study was conducted as a field study with an anthropological approach by means of participant observation, unstructured and semi-structured interviews and photography. RESULTS: The therapists in RAD work in isolation with little opportunity for further education or professional development. Their approach is mainly medical, where the work is dictated by the patients' expectations and doctors' recommendations. They use primarily passive methods of treatment, and their work is affected by cultural, religious and situational factors. They demonstrate a low capacity of clinical reasoning in their practical work. CONCLUSIONS: There is a need for further development of physiotherapy in Afghanistan. Active and individually adapted treatment methods, clinical reasoning processes and evidence-based practice should be encouraged. There are several challenges in this, based on Afghan culture and traditions, gender issues, religious factors, an authoritative society, a medical approach in treatment, and isolation and limitations in access to information. By means of an Action Research project the physiotherapists could be included in further development and research to promote a sustainable and culturally relevant development. PMID- 17852311 TI - Strategies for autonomy used by people with cervical spinal cord injury: a qualitative study. AB - PURPOSE: To identify strategies used by people with high cervical spinal cord injury (SCI) to function autonomously. A multidimensional concept of autonomy was used, with four dimensions: independence, self-determination, participation and identification. METHODS: Qualitative methods were used, involving literature study and semi-structured interviews with eight individuals with high SCI who had been discharged from the rehabilitation centre for several years and were members of a sports club. RESULTS: Strategies for independence included making independent functioning a personal challenge and learning from others with SCI. Strategies for self-determination included keeping oneself informed, setting personal goals and being assertive. Strategies for participation were making challenges out of barriers, planning and organizing, asking and accepting help, and dealing with reactions from others. Strategies for identification involved taking life as it comes and focussing on positive aspects of life. CONCLUSIONS: Different strategies are necessary for different dimensions of autonomy. Some strategies seem contradictory in terms of their effects on different dimensions of autonomy. Patients can be made aware of strategies for autonomy during the rehabilitation phase. PMID- 17852312 TI - A home-based rehabilitation program for the hemiplegic upper extremity by power assisted functional electrical stimulation. AB - PURPOSE: To assess the effects of daily power-assisted functional electrical stimulation (FES) home program therapy in chronic stroke. METHODS: A total of 20 consecutively enrolled stroke patients with spastic upper-extremity impairments > 1 year after stroke were recruited for this non-blinded randomized controlled trial. Subjects were assigned to control and FES groups and followed for 5 months. The FES group used a power-assisted FES device to induce greater muscle contraction by electrical stimulation in proportion to the integrated electromyography (EMG) signal picked up on surface electrodes. Target muscles were the extensor carpi radialis longus (ECRL) and extensor carpi radialis brevis (ECRB), extensor digitorum communis (EDC), extensor indicis proprius (EIP), and deltoid (Del). Patients underwent 30 approximately 60 min FES sessions at home about 6 days/week. Root mean square (RMS) of ECRL, EDC and Del maximum voluntary EMGs, active range of motion (ROM) of wrist and finger extension and shoulder flexion, modified Ashworth scale (MAS), and clinical tests were investigated before and after FES training. RESULTS: The FES group displayed significantly greater improvements in RMS, active ROM, MAS and functional hand tests, and was able to smoothly perform activities of daily life using the hemiplegic upper extremities. CONCLUSIONS: Daily power-assisted FES home program therapy can effectively improve wrist and finger extension and shoulder flexion. Proprioceptional sensory feedback might play an important role in power-assisted FES therapy. PMID- 17852313 TI - Gains and losses of structured information collection in the evaluation of 'rehabilitation in the community' programmes: ten lessons learnt during actual evaluations. AB - PURPOSE: Previously we have explored definitions of community-based rehabilitation (CBR) and proposed a way of classifying rehabilitation programmes by describing their essential characteristics. As the next step, we proposed two flow charts that guide the evaluator through a characterization of the programme and then indicate the information that should be collected. The present paper describes the application of this methodology in five actual evaluations of programmes aiming at socio-economic rehabilitation of persons affected by leprosy. METHOD: We compared the information as required by the flow charts to the information presented in the evaluation reports and asked: "Does this methodology adequately describe and reveal all relevant aspects of the rehabilitation programme?" RESULTS: Use of the flow charts led to discussion between evaluators and programme staff about how each would characterize the programme; this was a valuable step in the evaluation process and provided insight to the staff into their current practices and aspirations. The rehabilitation services as such were always well-described in the evaluation reports. More attention could have been given to the programme environment and provider-client relationships. More or more explicit attention than required by the flow charts could be given to linkages with other rehabilitation programmes and community organizations; questions of organizational capacity; systems to maintain and increase the quality of services; and conditions and constraints imposed by donor organizations. In order to show their effectiveness, rehabilitation programmes need to develop simple information systems which show progress of clients towards the rehabilitation goals defined for them, with them or by them. Impact can be demonstrated by an assessment one year after ending the intervention. This should include assessments of clients' psychological and social status. CONCLUSIONS: The original theoretical framework has proven its value in evaluation practice. The flow charts accommodate a variety of programmes and address the specific aims, contexts and developmental stages of the programmes evaluated. Taking the lessons learnt here into account will further improve the usefulness and practical relevance of the methodology we proposed. PMID- 17852314 TI - Validating the Falls Behavioural (FaB) scale for older people: a Rasch analysis. AB - PURPOSE: Rasch modelling was used to establish the validity and robustness of the Falls Behavioural (FaB) Scale for Older people. METHODS: The sample comprised 678 community-residing elderly people aged 65 - 98 years. Data were analysed by calculating goodness of fit statistics, principal components analysis of residuals and by exploring the effectiveness of the category rating response scale. RESULTS: A partial-credit rating scale was the best fitting solution and the major change to the original version of the FaB. Analysis supported a 29-item intervention version and a briefer 24-item outcome evaluation (research) version. The latter produced item mean infit statistics of 1.00 (Z = 0.0, SD = 0.33) and mean outfit statistics of 1.03 (Z = 0.0, SD = 0.53), a person separation of 2.36 and internal reliability of 0.85. CONCLUSION: The 29 item partial rating scale is valid, reliable and would be useful in clinical situations when used as a prompt for discussion and in raising clients' awareness of potential hazards; it also can be used as an outcome measure. The short form is a useful alternate for evaluating the effectiveness of fall reduction interventions that aim to encourage protective strategies when negotiating the environment, mobilizing and doing activities of daily living. Both scales would be improved by adding very difficult and very easy items to increase the range of ability levels of the people to whom it can be applied with precision. PMID- 17852315 TI - What can we learn from the personal insights of individuals living and coping with multiple sclerosis? AB - PURPOSE: The aim of this qualitative study was to explore the personal accounts of individuals with Multiple Sclerosis (MS). Hence the study presents individuals experiences of living with MS to date and the effective self-management strategies employed to cope in day-to-day life. METHODS: Thematic analysis was used to explore the personal narratives of thirteen individuals with MS in two focus group discussions. RESULTS: Participants in both groups identified similar themes related to the experiences of living and coping with MS. These were: Learning something was wrong (before diagnosis); getting a name (diagnosis); lack of professional support; unchanging family relationships, adjustments to employment circumstances and social life; challenges; successful coping via proactivity, perspective and control (self-management techniques); advice for others, and recommendations as to how services could be improved and developed. CONCLUSION: The most salient finding is that there is a need for a formal approach to the management of psychosocial problems and challenges associated with MS. This will require both users and health professionals working together to further the development of clinical guidelines and services for this population. PMID- 17852316 TI - Measuring participation of children with disabilities: issues and challenges. AB - PURPOSE: The aim of this paper is to examine conceptual issues that challenge development of valid and useful measures of children's participation. METHOD: Ambiguities in the current definition of participation in the International Classification of Functioning, Disability and Health (ICF) are examined along with their implications for developing valid measures for children and youth. RESULTS: Developers of new measures must address three key issues that will affect the ultimate meaning of participation data obtained from these instruments: uncertain criteria to distinguish activity from participation; lack of consensus on whether measures should address objective or subjective aspects of participation or both; and appropriate choice of respondent when children are the focus. Variations in how the participation construct is operationalized challenge one's ability to develop a coherent body of knowledge about children's participation and the factors that influence it. CONCLUSION: Given current variations in how participation is being defined, both developers and users of measures of participation need to be explicit about the definition of participation that a particular measure represents and the inferences that can be drawn from the scores. PMID- 17852317 TI - A computerised communication aid in severe aphasia: an exploratory study. AB - PURPOSE: To investigate the efficacy of TouchSpeak (TS), a handheld computerised communication aid for aphasia. METHOD: A pre-post one-group design was used with a referred sample of 34 patients with a severe aphasia and a need for alternative and augmentative communication (AAC). The participants were trained to use TS in two self-chosen communicative situations. The ability to navigate the hierarchical vocabulary and overall communicative ability were assessed. Participants rated their communicative success with and without TS. Three years after completion of the training, participants were interviewed about their present use of TS. RESULTS: In total, 76% used TS outside the clinic in two trained communicative situations. Overall communicative ability improved, as tested in untrained scenarios. Quality of communication with TS was rated higher than without TS. Fifty per cent obtained their own TS after the training and after 3 years 6% still used TS. CONCLUSIONS: Aphasic communication can be supported effectively by TS. Patients with a severe aphasia are able to master a hierarchical computerised vocabulary and to use it in daily life for specific communicative situations. In addition, TS may also have a generalised effect on overall communicative ability. For most patients, the supportive role of TS is temporary. PMID- 17852318 TI - The relative and absolute reliability of two balance performance measures in chronic stroke patients. AB - PURPOSE: To examine the relative reliability and absolute reliability of the Berg Balance Scale (BBS) and the Postural Assessment Scale for Stroke Patients (PASS) in chronic stroke patients. METHOD: A total of 52 mild to moderate stroke patients, who had a stroke more than 6 months previously, participated in the study. Both balance measures were administered twice, seven days apart, to the patients. A relative reliability index (intra-class correlation coefficient, ICC2,1) was used to examine the level of agreement between test and retest. Absolute reliability indices, including the Bland and Altman method, the standard error of measurement (SEM), and the smallest real differences (SRD), were used to define the extent to which a balance score varies on test-retest measurements. RESULTS: Test-retest agreements were high (ICC2,1: BBS = 0.98; PASS = 0.97), indicating excellent agreement from a relative perspective. The SEM of the BBS and PASS, representing the smallest change threshold that indicates a real improvement for a group of individuals, were 2.4 and 1.1, respectively. The SRD of the BBS and PASS were 6.7 and 3.2, respectively, exhibiting the smallest change threshold that indicates a real improvement for a single individual. CONCLUSIONS: The test-retest agreements of the BBS and PASS were high in mild to moderate chronic stroke patients. The thresholds of both measures to detect real change are acceptable in research and clinical settings. PMID- 17852319 TI - Survey of the current status of cancer rehabilitation in Japan. AB - PURPOSE: To elucidate the current status of cancer rehabilitation in institutions nationwide. METHOD: A questionnaire survey regarding the current status of cancer rehabilitation in 1693 healthcare institutions was conducted by mail. The survey first asked whether rehabilitation was being conducted for cancer patients and, in facilities in which it was being conducted, it then asked about the content of the rehabilitation, the stage of the cancer patients, etc. Facilities in which cancer rehabilitation was not being conducted were surveyed in regard to whether there was a need for cancer rehabilitation. RESULTS: Valid replies were obtained from 1045 (62.0%) institutions and 864 (82.7%) of them conducted rehabilitation for cancer patients. A high proportion of the content of the rehabilitation was found to be related to physical function. Activities of daily living guidance and training were also found to be conducted in a high proportion. Low proportions of the facilities conducted content that was specialized for cancer. Of the 181 facilities in which rehabilitation was not being conducted for cancer patients, 171 (94.5%) replied that they felt that rehabilitation was needed for cancer patients. CONCLUSIONS: Based on the results of this fact-finding survey it will be necessary to consider strategies for popularizing and developing rehabilitation programmes for cancer patients in Japan. PMID- 17852320 TI - Development of a tool to guide referral of patients with neuromuscular disorders to allied health services. Part one. AB - PURPOSE: Reasons for referral of patients with chronic, slowly progressive neuromuscular disorders (NMD) to occupational therapy (OT), physical therapy (PT) and speech therapy (ST) are often unclear. One-off consultations by OT, PT and ST can help patients and physicians to decide if therapy is needed. We present a construct for a questionnaire, the Perceived Limitations in Activities and Needs Questionnaire (PLAN-Q). Its aim is to signal problems and needs of patients with chronic, slowly progressive NMD with a view to referral for one-off consultations by OT, PT and ST. We report on the construct, item pool, response options and the item reduction procedure as the first development stages for the PLAN-Q. METHODS: The International Classification of Functioning, Disability and Health (ICF) served as source for items and response options. Five clinical health professionals of the Neuromuscular Center Nijmegen (NMCN) formed an expert panel. They were asked to reach consensus on construct, item pool and response options. Subsequently a sample of patients with NMD (n=21) that attended the NMCN was asked for their approval of the concept questionnaire. Data of a large cohort (n=208) of patients with a broad variety of chronic NMD were used to carry out item reduction. RESULTS: The expert panel reached consensus on the selection of 56 items covering eight activity categories relevant to OT, PT, and ST. They also reached consensus on response options regarding 'capacity' and 'need for therapy or advice'. The patient sample approved the concept PLAN-Q. The item reduction procedure resulted in a reduction to 25 items covering eight activity categories. CONCLUSION: The PLAN-Q has proceeded through the first stages of development and is now ready for further assessment of reliability and validity. PMID- 17852321 TI - Feasibility of a new community-based geriatric intervention programme: an exploration of experiences of GPs, nurses, geriatricians, patients and caregivers. AB - PURPOSE: To determine the feasibility of the Dutch Geriatric Intervention Programme (DGIP) in primary care. Within the DGIP, a nurse cooperates with a General Practitioner (GP) and a clinical geriatrician to assess and manage care for community-living older patients. The aim of this study was to describe both views of care receivers and those of professionals in order to identify facilitating factors and barriers for implementation of the DGIP. METHOD: Combined quantitative and qualitative data collection methods were used. Pre- and post-questionnaires were taken from GPs (n= 15), nurses (n = 6) and geriatricians (n = 2). These professionals were also interviewed. In addition patients (n = 11 out of total n = 54) and their carers (n = 37) were interviewed. RESULTS: GPs appreciated the support by the DGIP for problems in cognition, mood and mobility. Lack of knowledge and time restriction was the cause of their incapability at that point. In the cooperation between professionals, nurses felt that they had to initiate the contact. Personal contact helped the mutual communication. Involving the carer of the patient proved very important. All disciplines found this of crucial importance in order to deliver a tailored intervention and create conditions for optimal care. Barriers, for which the programme was tailored during the implementation, were: resistance in referrals of patients to the programme, nurses' and GPs' knowledge of diagnostic tests, communication problems and insufficient involvement of caregivers. CONCLUSIONS: The implementation of the DGIP was feasible, but several barriers need ongoing attention by implementation, like communication between disciplines. PMID- 17852322 TI - Development of a tool to guide referral of patients with neuromuscular disorders to allied health services. Part two. AB - PURPOSE: The Perceived Limitations and Needs Questionnaire (PLAN-Q) was developed to guide referral for a one-off consultation by occupational therapy (OT), physical therapy (PT), and speech therapy (ST) consultation, to provide a tailor made advice on allied health interventions. This article reports on the testing of validity and reliability of the PLAN-Q. METHODS: In the validation study, 208 patients with a broad spectrum of neuromuscular disorders completed the PLAN-Q, Medical Outcome Study short-form 36-item version (SF-36), and the Impact of Participation on Autonomy (IPA) questionnaires. A subsection of 51 patients, whose physical condition was stable, participated in the evaluation of the intra rater reliability of the questionnaire. The theoretical construct was tested with factorial analysis, subscales were constructed and reliability and validity of the PLAN-Q subscales were assessed. RESULTS: Factorial analysis resulted in an 18 item self-report questionnaire. Items were grouped into four subscales ('physical capacity', 'transferring', 'oropharyngeal capacity', and 'hand-use'), each with two dimensions ('capacity' and 'need for help'). The internal consistency of all subscales was good (Cronbach's alpha: 0.77-0.94) as well as the intra-rater reliability of the subscales 'physical capacity' and 'transferring' in the 'capacity' dimension (Kappa: 0.70-0.75). The 'need' dimension showed poor intra rater reliability suggesting that 'need for help' is a variable phenomenon that changes between two points of measurement. The construct validity of the subscales against the SF-36 and the IPA was satisfactory. CONCLUSION: The PLAN-Q is a valid self-report instrument that measures patients' perception of capacity and needs in domains relevant to referral for a one-off OT, PT, or ST consultation. PMID- 17852324 TI - Using stroke to explore the life thread model: an alternative approach to understanding rehabilitation following an acquired disability. AB - The purpose of this paper is to introduce the Life Thread Model, which incorporates established psychological and social theory related to identity change following an acquired disability. It is supported by a growing body of empirical evidence and can be used to broaden our understanding of service provision in rehabilitation. We suggest that a limited appreciation of social and psychological processes underpinning rehabilitation has led to different agendas for patients and professionals, lack of recognition of power relationships, negative views of disability, and insufficient professional knowledge about the management of emotional responses. The Life Thread Model, based on narrative theory and focusing on interpersonal relationships, has been developed following ten years of empirical research. Using the model, the balance of power between professionals and patients can be recognized. We suggest that positive emotional responses can be supported through (a) endorsing a positive view of self, (b) 'being' with somebody as well as 'doing' things for them; and (c) seeing acquired disability as a time of transition rather than simply of loss. This model highlights the usually hidden social processes which underpin clinical practice in acquired disability. Recognition of the importance of discursive as well as physical strategies widens the possibilities for intervention and treatment. PMID- 17852325 TI - Work and recreational changes among people with neurological illness and their caregivers. AB - BACKGROUND: Progressive neurological illnesses alter the health and well-being of people who experience them, and frequently lead to changes in the activities of both patients and their carers. Purpose. The current study investigated changes in work and recreational activities among people with four of these illnesses. METHOD: In total, the following numbers of people with neurological illnesses and their carers participated in the study: 28 with multiple sclerosis; 27 with motor neurone disease; 31 with Parkinson's; and 24 with Huntingtons disease. In addition, 28 professionals who worked with these populations participated in the study. Individual interviews were conducted with each of the above respondents to determine the impact of the neurological illness. RESULTS: The results demonstrated a high level of agreement from each of the participants. Most of the people with the illnesses and many of the carers had reduced their level of paid work. Generally, all groups of respondents perceived these changes as being negative. Changes in recreational activities were also seen to be primarily negative. CONCLUSIONS: These results are discussed in terms of proposed prevention and intervention programmes to prepare patients and their carers for the changes that result from the neurological illness, strategies to stay at work longer and to help them develop alternative strategies to assist them in filling the gap left in their lives that was previously occupied by paid work. PMID- 17852326 TI - Therapeutic effects of electrical stimulation on manual function of children with cerebral palsy: evaluation of two cases. AB - PURPOSE: To investigate changes in hand function associated with electrical stimulation for children with hemiplegic cerebral palsy. METHOD: An ABCA single subject design, replicated in two children, was used in this study. Each baseline (phase A) lasted 4 weeks. Intervention consisted of electrical stimulation of wrist extensors (phase B) and of wrist extensors and flexors (phase C) for 15 minutes three times a week. Intervention phases also lasted 4 weeks. Active wrist extension range of movement and three timed manual tasks were tested two times a week every week. Data analysis included the Celeration Line and Two Standard Deviation Band methods in addition to visual analysis. RESULTS: Significant performance gains were observed for both children, especially in phase C, when both extensors and flexors were stimulated. After intervention withdrawal, significant performance decreases were observed on most analysed variables. CONCLUSIONS: The observed performance changes seem to be associated with the presence of intervention and suggest that electrical stimulation can be a useful adjunct to improve hand function of children with cerebral palsy. PMID- 17852328 TI - Cloning and comparative bioinformatic analysis of feline glucose-6-phosphatase catalytic subunit cDNA. AB - Glucose-6-phosphatase is a multicomponent enzyme composed of a transporter subunit and a catalytic subunit that is involved in hepatic glucose production. The objective of the present study was to determine the complete nucleotide sequence of feline hepatic glucose-6-phosphatase catalytic subunit (G6Pc) cDNA and to perform comparative analysis of the molecular features of the feline G6Pc cDNA and protein. Feline G6Pc cDNA contains 2261 bases and encodes a 357 aa protein. The feline cDNA and protein are highly conserved with overall identity ranging from 73-86% to 86-95%, respectively, among mammalian species. Membrane topology, phosphatase consensus sequence, ER retention sequence, N-glycosylation sites and active site residues are conserved in the feline protein. Analysis of the putative feline G6Pc protein did not reveal any species-specific features to explain the unusual in vivo regulation of G6Pase activity reported in feline liver. PMID- 17852329 TI - Complete nucleotide mtDNA sequence of Barbary sheep (Ammotragus lervia). AB - In this report we describe the complete sequence of the mtDNA genome of Ammotragus lervia (Barbary sheep or aoudad) as obtained by PCR and sequencing with primer walking using flanking sequences. The molecule is 16,530 base pairs in length, resulting similar to those of goat and sheep. The genome organization matches to those of other mammalian mitochondrial genomes. The phylogenetic position of the Ammotragus relative to twelve other mammalian species was assessed based on protein-coding sequences. A goat-aoudad split of 9.9-8.9 MYBP has been estimated, whereas the divergence ancestor/caprines was dated at 12.1 10.8 MYBP. PMID- 17852330 TI - Cloning, genomic organization and expression of two glycosyl hydrolase family 10 (GHF10) genes from golden apple snail (Pomacea canaliculata). AB - Two cellulase cDNAs (GHF10-Pc1 and GHF10-Pc3) belonging to glycoside hydrolase family 10 (GHF10) were successfully isolated and characterized from stomach tissue of golden apple snail (Pomacea canaliculata), a kind of herbivorous mollusca. Sequencing analysis revealed full-length cDNAs of 1300 and 1277 bp in length, respectively. The open reading frame (ORF) of cellulase cDNA was 1188 and 1191 bp, encoding 395 and 396 amino acid, respectively. Sequence alignment revealed that GHF10-Pc1 and GHF10-Pc3 shared high identity with glycosyl hydrolase family 10 (GHF10) and had an overall similarity of 98 and 82% to those of Ampullaria crossean cellulase EGX. A neighbour-joining tree showed a clear differentiation between each species and also indicated that GHF10-Pc1 and GHF10 Pc3 from P. canaliculata and A. crossean EGX are closely related phylogenetically. The genomic organization of cellulase GHF10-Pc1 and GHF10-Pc3 genes was also investigated. The GHF10-Pc1 and GHF10-Pc3 genes spanned over 4937 and 4512 bp, respectively. Both genes contained 9 exons interrupted by eight introns. The result verified the endogenous origin of the GHF10-Pc1 and GHF10-Pc3 genes. Analysis of RNA by RT-PCR from several ages of P. canaliculata revealed that neither gene was expressed in eggs. GHF10-Pc1 was also expressed in 1- and 10-day-old juvenile snails whereas GHF10-Pc3 was expressed only in 1-day-old juvenile snails. The result showed that two GHF10-Pc transcripts were developmentally expressed. PMID- 17852331 TI - Cloning and characterization of the rabbit POU5F1 gene. AB - The product of the POUSF1 gene, Oct4, plays an important role both in embryonic development and in the self-renewal and differentiation of totipotent cells. To understand the function of Oct4 in rabbit ES cells, we cloned and sequenced the rabbit POU5F1 gene, as well as the cDNA encoded by the gene. The Oct4 cDNA contains a 1083 bp ORF encoding a 360 aa protein and a 241 bp 3' UTR sequence. Oct4 mRNA was expressed at a high level in rabbit ES cells and was barely detectable in the adult spleen, kidney, brain and muscle tissues. The POU5F1 gene is approximately 6 kb in length and includes five exons and four introns. Gene organization is similar to that of the mouse, human and bovine orthologs. Sequencing of the gene revealed an 82% (mouse), 90% (human) and 89% (bovine) overall identity at the protein level. The rabbit POUSF1 gene was mapped to chromosome 12q1.1 by PCR amplification of DNA from two putative POU5F1-containing BAC clones, which were previously mapped to chromosome 12q1.1. The cloning of the rabbit POU5F1 gene will facilitate studies on its roles in rabbit embryogenesis and ES cells. PMID- 17852332 TI - Identification of a gene encoding the light-harvesting chlorophyll a/b proteins of photosystem I in green alga Dunaliella salina. AB - There are four LhcII genes of Dunaliella salina have been submitted to the database of GenBank. However, little is known about Lhca genes of this green alga, although this knowledge might be available to study the composition and phylogenesis of Lhc gene family. Recently, one Lhca gene was been cloned from the green alga D. salina by PCR amplification using degenerate primers. This cDNA, designated as DsLhca1, contains an open reading frame encoded a protein of 222 amino acids with a calculated molecular mass of 27.8 kDa. DsLhca1 is predicted to contain three transmembrane domains and a N-terminal chloroplast transit peptide (cTP) with length of 33 amino acids. The genomic sequence of DsLhca1 is composed of five introns. The deduced polypeptide sequence of this gene showed a lower degree of identity (less than 30%) with LHCII proteins from D. salina. But its homology to Lhca proteins of other algae (Volvox carteri Lhca_AF110786) was higher with pairwise identities of up to 67.1%. Phylogenetic analysis indicated that DsLhcal protein cannot be assigned to any types of Lhca proteins in higher plants or in Chlamydomonas reinhardtii. PMID- 17852333 TI - Characterisation of the warm acclimated protein gene (wap65) in the Antarctic plunderfish (Harpagifer antarcticus). AB - Physiological adaptation to increased environmental temperatures has been studied experimentally in a number of fish species, with the up-regulation of several genes identified as being associated with the process, such as the warm acclimated protein (wap65). This article describes the cloning and characterisation of the wap65-2 gene from the Antarctic plunderfish (Harpagifer antarcticus). The transcriptional expression of this gene in response to elevated seawater temperatures over a time course series is presented. Initially there is strong down-regulation of this gene to a maximum of 40-fold within 4 h, followed by recovery to almost control levels within 48 h, indicating that this gene does not play a role in the potential temperature adaptation of H. antarcticus. PMID- 17852334 TI - Identification and cloning of a novel tetraspanin (TSP) homologue from Brugia malayi. AB - This is the first report of a tetraspanin (TSP)-like molecule in the lymphatic filarial parasites. Expressed sequence tag (EST) database search for TSP like molecules in the filarial genome resulted in three significant EST hits (two partial ESTs from Brugia malayi and one full length EST from Wuchereria bancrofti). The full length gene cloned from B. malayi showed significant similarity to Caenorhabditis elegans TSP and human TSP and hence the gene was named B. malayi TSP (BmTSP). Subsequent Genbank analysis with the predicted ORF of BmTSP showed additional homologous genes reported from Schistosoma mansoni and Taenia solium parasites. Structural analyses showed that BmTSP has four transmembrane domains and other conserved domains such as CCG and two other critical cysteine residues present within the large extracellular loop similar to other reported TSPs. In addition, putative post-translational modifications such as N-glycosylation, protein kinase c phosphorylation, casein kinase II phosphorylation and N-myristoylation sites have been found in BmTSP sequence. Further, PCR analyses showed that BmTSP is differentially transcribed, with highest level of expression being present in the adult stages followed by L3 and mf stages. This study thus describes a novel TSP cloned from B. malayi, its putative functions in cuticle biogenesis and role in protective immunity. PMID- 17852335 TI - Evolution and expression of gamma-aminobutyric acid type A receptor-associated protein from the amphioxus Branchiostoma belcheri. AB - The cDNA encoding a gamma-aminobutyric acid type A (GABA(A)) receptor-associated protein (GABARAP) was identified from the gut cDNA library of amphioxus Branchiostoma belcheri. It consisted of 1246 bp with a 354 bp open reading frame coding for a 117 amino acids protein of 13.9 kDa. The phylogenetic tree analysis showed that amphioxus GABARAP clustered with GABARAPs, separating from GABARAP like proteins including amphioxus GABARAPL2. Amphioxus GABARAP gene had an exon intron organization similar to human, mouse, zebrafish and sea squirt GABARAP homologs in terms of both exon number and sequence homology of each exon, hinting at the clue that GABARAP gene transcription is regulated similarly in all the chordates. In situ hybridization histochemistry revealed a ubiquitous expression pattern of amphioxus GABARAP gene, although it was temporally expressed specifically in the primitive gut of 2- to 10-day larvae, suggesting a conserved role of GABARAP in amphioxus as well as in mammalian species. PMID- 17852336 TI - Human interferon regulatory factor-1 gene and its promoter sequences revealed by population-based complete gene sequencing. AB - Interferon regulatory factor-1 (IRF-1) plays important roles in host immunity, cell proliferation and apoptosis. The current GenBank sequence for human IRF-1 (accession number: L05072) was derived from a human placenta DNA library and reported in 1992. In one recent population-based sequence study, we observed consistent discrepancies between our IRF-1 sequence data and GenBank reference sequences suggesting that, current IRF-1 reference sequence was not representative for all populations. By complete gene sequencing, we obtained a representative full-length IRF-1 sequence from a single subject. Compared to submission L05072, our population-based data contains: 35 nucleotide additions, 8 nucleotide removals and another 12 nucleotide replacements. A single nucleotide difference was observed in the IRF-1 promoter sequence compared to GenBank sequence (X53095). These changes were confirmed in 350 Kenyans and 28 non-African donors. The accuracy of a reference sequence is crucial for downstream genetic and functional studies and this study provides more complete and accurate data on the sequence of the human IRF-1 gene and its immediate promoter region. PMID- 17852337 TI - Mapping two genes in the purine metabolism pathway of soybean. AB - Mapping genes in biochemical pathways allow study of the genomic organization of pathways and geneic relationships within these pathways. Additionally, molecular markers located within the boundaries of a specific gene sequence represent important marker assisted selection resources. We report map locations of two geneic markers from the purine synthesis pathway in soybean (Glycine max (L. merr.)), utilizing a 90 plant F(2) population created from the cross of "DT97 4290" x "DS97-84-1". Primers were designed based on sequences from annotated soybean complimentary DNA. A polymorphic, co-dominant, sequence-characterized amplified region marker was created for hypoxanthine phosphoribosyl transferase (EC 2.4.2.8). Linkage analysis placed this gene on linkage group (LG) O. In addition, a single-nucleotide polymorphism (SNP) marker was developed for a urate oxidase gene (EC 1.7.3.3). Linkage analysis of the SNP placed the urate oxidase gene on LG I. For both genes, amplicon sequence data confirmed the identification of the respective gene. Mapping these genes represents the first step in understanding the genomic organization of the purine biochemical pathway in soybean. PMID- 17852338 TI - The narQP genes for a two-component regulatory system from the deep-sea bacterium Shewanella violacea DSS12. AB - Shewanella violacea DSS12 is facultative piezophile isolated from the deep-sea. The expression of cydDC genes (required for d-type cytochrome maturation) of the organism is regulated by hydrostatic pressure. In this study, we analyzed the nucleotide sequence upstream of cydDC in detail and found that there are putative binding sites for the NarL protein which is part of a two-component regulatory system also containing the sensor protein NarX. Furthermore, we identified the narQP genes (homologues of narXL) from S. violacea DSS12 and demonstrated the heterologous expression of narP in Escherichia coli. These results will be helpful in examining pressure regulation of gene expression in S. violacea at the molecular level. PMID- 17852339 TI - Molecular characters and expression analysis of the gene encoding eclosion hormone from the Asian corn borer, Ostrinia furnacalis. AB - Using rapid amplification of cDNA ends (RACE), the cDNA encoding eclosion hormone (EH) was cloned from the brain of Ostrinia furnacalis. The full Osf-EH cDNA is 986 bp and contains a 267 bp open reading frame encoding an 88 amino acid preprohormone, which including a hydrophobic 26 amino acid signal peptide and a 62 amino acid mature peptide. The mature Osf-EH shows high identity with Manduca sexta (95.2%), Helicoverpa armigera (91.9%) and Bombyx mori (85.5%), but low identify with Tribolium castaneum (63.6%), Drosophila melanogaster (56.5%) and Apis mellifera (54.8%). Using the HMMSTR Prediction Server, the 3D structure of Osf-EH was modeled. There are four beta-turns and three alpha-helixes predicted in Osf-EH, with the pattern of beta-beta-alpha-alpha-beta-beta-alpha. Northern blot analysis indicated a 1.0 kb transcript present only in the brain. The Osf-EH mRNA can not be detected in other neural tissues, such as the suboesophageal ganglion, thoracic ganglion, abdominal ganglion and other non-neural tissues, such as the midgut, fat body and epidermis. The Osf-EH mRNA content in the brain was measured using the combined method of quantitative RT-PCR and Southern blotting, which reached its highest level the day before the molt. PMID- 17852340 TI - Genome-wide analysis of SINA family in plants and their phylogenetic relationships. AB - SINA genes in plants are part of a multigene family with 5 members in Arabidopsis thaliana, 10 members in Populus trichocarpa, 6 members in Oryza sativa, at least 6 members in Zea mays and at least 1 member in Physcomitrella patens. Six members in maize were confirmed by RT-PCR. All SINAs have one RING domain and one SINA domain. These two domains are highly conserved in plants. According to the motif organization and phylogenetic tree, SINA family members were divided into 2 groups. In addition, through semi-quantitative RT-PCR analysis of maize members and Digital Northern analysis of Arabidopsis and rice members, we found that the tissue expression patterns are more diverse in monocot than in Arabidopsis. PMID- 17852341 TI - Molecular characterization of cDNA encoding B. taurus cathelicidin-7 like antibiotic peptide from bone marrow cells of Bubalus bubalis. AB - Cathelicidins represent a diverse family of endogenous cationic antibiotic peptide present in all mammalian species. In the present study, a novel cathelicidin cDNA was identified and characterized from bone marrow cells of buffalo (Bubalus bubalis) using RT-PCR based approach. The cDNA encodes a propeptide of 1.18 kDa with net positive charge at neutral pH. The precursor peptide possesses a signal peptide of 29 amino acids and a biologically active peptide of 34 residues. Comparison of sequences indicates only 66.1 and 64.1% identity at nucleotides and amino acids level respectively, with the already reported cathelicidin congener from the same species. However, high degree of similarity (92.8% nucleotides and 81.9% amino acids) was noticed with cathelicidin 7 sequence of Bos taurus suggesting interspecies conservation of cathelicidin peptides rather than intra-species within bovidae family. Phylogenetic trees analyses also support these data. Our findings, further justify the cloned cDNA as a unique cathelicidin member of B. bubalis, and may reasonably considered to be another example of structural diversity exhibited by cathelicidin-derived peptides as reported from other mammals. PMID- 17852342 TI - Molecular cloning and characterization of a transferrin cDNA from the white spotted flower chafer, Protaetia brevitarsis. AB - A full-length cDNA clone with high homology to insect transferrin genes was cloned by screening a Protaetia brevitarsis cDNA library. This gene (PbTf) had a total length of 2338 bp with an open reading frame (ORF) of 2163 bp, and encoded a predicted peptide of 721 amino acid residues. Like known cockroach, termite, and beetle transferrins, PbTf appears to have residues comprising iron-binding sites in both N- and C-terminal lobes. The deduced amino acid sequence of the PbTf cDNA was closest in structure to the beetle Apriona germari transferrin (68% protein sequence identity). Northern blot analysis revealed that PbTf exhibited fat body-specific expression and was upregulated by wounding, bacterial or fungal infection and iron overload, suggesting a functional role for PbTf in defense and stress responses. PMID- 17852343 TI - Isolation and characterization of two distinct classes of DXS genes in Hevea brasiliensis. AB - Two cDNAs encoding two distinct classes of DXSs were cloned from leaves (HbDXS1) and latex (HbDXS2) of Hevea brasiliensis by RT-PCR based methods. HbDXS1 encodes a protein of 720 amino acids, with a high homology to the class I of plant DXS proteins, and HbDXS2 encodes a protein predicted to contain 711 amino acids and with a high homology to the plant DXS class II proteins. Several important motifs and amino acid positions characteristic of DXS proteins are strictly conserved in both new HbDXS proteins. The two HbDXS genes were differentially expressed in various tissues of H. brasiliensis. The transcriptional levels of HbDXS2 were similar in both a high-yielding rubber clone (RRIM 600) and the wild type. Ethephon increased the latex yield and caused a transient increase of expression of the HbDXS2 gene. The expression of HbDXS2 in latex indicates that it may have a primary function in carotenoid biosynthesis rather than for natural rubber. PMID- 17852344 TI - Identification of coding polymorphisms in human circadian rhythm genes PER1, PER2, PER3, CLOCK, ARNTL, CRY1, CRY2 and TIMELESS in a multi-ethnic screening panel. AB - STUDY OBJECTIVE: In this study, the exonic regions of the circadian rhythm genes PER1, PER2, PER3, CLOCK, ARNTL, CRY1, CRY2 and TIMELESS were re-sequenced and coding changes identified in a panel of 95 individuals varying in ethnicity. STUDY PARTICIPANTS: DNA screening panel consisting of 95 DNA samples (17 American Caucasians, 17 African Americans, 8 Ashkenazi Jews, 8 Chinese, 8 Japanese, 5 Mexican Indians, 8 Mexicans, 8 Northern Europeans, 8 Puerto Ricans, and 8 South Americans) selected from the Coriell Institute Human Variation Panel. RESULTS: In addition to coding changes already identified in the database dbSNP, novel coding changes were identified, including PER1: Pro37Ser, Pro351Ser, Gln988Pro, Ala998Thr; PER2: Leu83Arg, Leu157Leu, Thre174Ile, Phe400Phe, Pro822Pro, Ala828Thr, Ala861Val, Phe876Leu, Val883Met, Val903Ile, Ala923Pro; PER3: Pro67Pro, Val90Ile, His638His, Ala820Ala, Leu929Leu; ARNTL: Arg166Gln, Ser459Phe; CLOCK: Ala34Ala, Ser208Cys, Phe233Phe, Ser632Thr, Ser816Ser; TIMELESS: Met870Val and CRY2: His35His. No coding polymorphisms were identified in CRY1. CONCLUSIONS: Considerable genetic variation occurs within the coding region of the genes regulating circadian rhythm. Many of the non-synonymous coding polymorphisms could affect protein structure/function with the potential to affect molecular regulation of the sleep/wake cycle. Many of the potential functional effects could be ethnic group specific. PMID- 17852345 TI - Molecular cloning and characterization of rat chitotriosidase. AB - Recent year some members of mammalian chitinases and chitinase-like proteins have been discovered, but rat counterpart of human and mouse chitotriosidase has not been identified. Moreover, the physiological functions of mammalian chitinases are not very clear. To facilitate the studies we cloned the cDNA encodes the rat chitotriosidase. The results revealed that it is differ from mouse and human chitotriosidase genes, it exist alternative splicing transcripts in several tissues we detected due to different transcriptional initiation sites and different exon usage, although all the open reading frame of these cDNAs predict a protein of 464 amino acids with a typical chitinase structure, including a signal peptide, a highly conserved catalytical domain and a chitin-binding structure. The predicted amino acid sequence is highly homologous to that of mouse and human chitotriosidase. Recombinant expression of the cloned cDNA demonstrated that the encoded protein is secreted extracellularly and has chitinolytic activity. PMID- 17852346 TI - Characterization of phosphatidylinositol-glycan biosynthesis protein class F gene in rice. AB - The glycosylphosphatidylinositol (GPI) anchors are linked to glycosylphosphatidylinositol-anchored proteins (GAPs) which are essential for the growth of mammalian, yeast and protozoan cells. The GPI anchor is covalently linked to GAP by amide bond formation between the carboxyl terminus and phosphoethanolamine attached at the third mannose and mediated by a transamidase complex. Mediation of GPI synthesis is by the sequential additions of GPI-N acetylglucosaminyltransferase (GPI-GnT) complex, the GlcN-PI de-N-acetylase, the GlcN-PI mannosyltransferases and the GPI lipid anchor phosphoethanolamine transferase complexes. We report a rice gene OsPIG-F that encodes a homolog to the human PIG-F protein, one of GPI lipid anchor phosphoethanolamine transferase complexes. The amino acid sequences of rice PIG-F consisted of six helix transmembrane domains, one glycosaminoglycan attachment site, one cGMP-dependent protein kinase phosphorylation site and a protein C phosphorylation site at the C terminus. This unique structure of rice PIG-F indicates the typical membrane bound structure of a protein. Polyclonal antibody for rice PIG-F was found to be cross-reactive with a protein extracted from the leaves of rice. The levels of rice PIG-F transcripts were found to be abundant in leaves, moderately in the milky stage of seed development and less in the floral spikelet, indicating that the rice PIG-F gene was differentially regulated in specific tissues. Furthermore, the levels of rice PIG-F transcription were up-regulated by growth hormones including GA(3), NAA and kinetin. These results indicated that the rice PIG-F gene expression may medicated by these growth regulators. PMID- 17852347 TI - Bluetongue virus serotype 17 sequence variation associated with neutralization. AB - Bluetongue virus (BTV) is an insect-transmitted orbivirus of importance to the cattle and sheep industry. The VP2 protein, encoded by L2, contains neutralizing epitopes. Previously, a panel of neutralizing monoclonal antibodies (MAbs) to the BTV serotype 17 (BTV-17) prototype strain was generated and it was determined that the neutralization domain consists of three overlapping epitopes. Over 30 amino acid changes were found between a neutralized BTV-17 prototype strain and a non-neutralized BTV-17 198 strain. In this study, the L2 genes from eight additional strains, representing both the neutralized and non-neutralized groups of BTV-17, were sequenced to determine the degree of conservation of the previously characterized differences. Comparison of the deduced amino acid sequences showed that 91% (30/33) of the previously noted changes were conserved within each group. The sequence of the M5 gene that encodes VP5 was also examined, since this surface protein has also been shown to affect neutralization. No consistent changes were noted between the neutralized and non neutralized groups of BTV-17 by analysis of the VP5 protein. Finally, the L2 sequences of five MAb neutralization escape mutants were determined to identify specific amino acids involved in neutralization and perhaps virulence. All five mutants contained 1-3 amino acid changes that were in close proximity to a previously described variable region. These amino acid changes likely define critical sites in the overlapping neutralization domains previously described. This is the first description of two BT virus populations that have distinct neutralization characteristics co-circulating in a defined geographical region. PMID- 17852348 TI - Cloning and characterization of TsMT3, a type 3 metallothionein gene from salt cress (Thellungiella salsuginea). AB - A full-length type 3 plant metallothionein cDNA was isolated from 200 mM NaCl stressed shoots of the salt cress (Thellungiella salsuginea). The 447 bp TsMT3 cDNA sequence has a 207 bp open reading frame (ORF) and encodes a deduced 69 residue peptide of molecular weight 7.52 kDa. Southern blot analysis indicates that, there is only one copy of TsMT3 in the T. salsuginea genome. The accumulation of TsMT3 mRNA is enhanced by the stress imposed by PEG6000, 200 mM NaCl, 50 microM ABA, 4 degrees C, 40 microM CuSO(4) or 25 microM CdCl2. The expression vector pET28-TsMT3 was heterologously expressed in Escherichia coli to define the contribution of TsMT3 to heavy metal tolerance. In the presence of 2 mM CuSO4, 0.3 mM Pb(NO3)2 or 0.4 mM CdCl2, TsMT3 expressing cells exhibited enhanced metal tolerance and accumulated more metal than the controls. We believe that TsMT3 is probably involved in the processes of metal homeostasis, tolerance, and reactive oxygen species (ROS) scavenging. PMID- 17852349 TI - Molecular cloning and characterization of the gene encoding squalene epoxidase in Panax notoginseng. AB - Squalene epoxidase (SE) is one of the rate-limiting enzymes in the triterpene saponins biosynthetic pathway. Panax notoginseng, one of the famous medicinal plants in China, produces bioactive triterpene saponins. Here we report the P. notoginseng SE, which was cloned from the root of P. notoginseng by PCR. The nucleotide sequence of the ORF (GenBank accession no. DQ386734) contains 1611 nucleotides and encodes 537 amino acid residues with molecular weight of 59.14 kDa and pI of 8.81. The gene has 98% identity with P. ginseng but different identities with other SE families. P. notoginseng SE has a FAD function domain, NAD(P)-binding Rossmann-fold domains, hydrophobicity and 4 transmembrane helices. This SE may be a microsomal membrane-associated enzyme. Real time quantitative PCR shows that the cDNA has different expression pattern and is highly expressed in root, especially in 3-year-old root. PMID- 17852350 TI - Characterization and phylogeny of two beta-cytoskeletal actins from Hemibarbus mylodon (Cyprinidae, Cypriniformes), a threatened fish species in Korea. AB - Complementary DNA and genomic sequences representing two different beta-actins were isolated from a threatened freshwater fish species Hemibarbus mylodon. The beta-actin 1 and 2 encoded an identical number of amino acids (375 aa), and shared 88.8 and 99.7% of identity at coding nucleotide and amino acid levels, respectively. Genomic open reading frame (ORF) sequences of both isoforms contained five translated exons interrupted by four introns with conserved GT/AG exon/intron boundary rule. Semi-quantitative RT-PCR showed that the two isoform mRNAs were ubiquitously detected in all tissues tested, but transcript levels were variable across tissues. Phylogenetic analysis showed that H. mylodon beta actin 1 and 2 were clustered into two distinct major and minor branches of Cypriniformes, respectively. Comparisons of the 5'-upstream region and 3'-UTR of H. mylodon beta-actin 1 also showed a high degree of homology with those of the major teleost beta-actins and warmblooded vertebrate beta-cytoskeletal actins, suggesting their more recent common origin. PMID- 17852351 TI - Sequence and organization of the complete mitochondrial genomes of spotted halibut (Verasper variegatus) and barfin flounder (Verasper moseri). AB - In this work, the mitochondrial genomes for spotted halibut (Verasper variegatus) and barfin flounder (Verasper moseri) were completely sequenced. The entire mitochondrial genome sequences of the spotted halibut and barfin flounder were 17,273 and 17,588 bp in length, respectively. The organization of the two mitochondrial genomes was similar to those reported from other fish mitochondrial genomes containing 37 genes (2 rRNAs, 22 tRNAs and 13 protein-coding genes) and two non-coding regions (control region (CR) and WANCY region). In the CR, the termination associated sequence (ETAS), six central conserved block (CSB A,B,C,D,E,F), three conserved sequence blocks (CSB1-3) and a region of 61-bp tandem repeat cluster at the end of CSB-3 were identified by similarity comparison with fishes and other vertebrates. The tandem repeat sequences show polymorphism among the different individuals of the two species. The complete mitochondrial genomes of spotted halibut and barfin flounder should be useful for evolutionary studies of flatfishes and other vertebrate species. PMID- 17852352 TI - Cloning and expression pattern of SsHKT1 encoding a putative cation transporter from halophyte Suaeda salsa. AB - Potassium is an essential element for plant, and high-affinity K+ uptake system plays a crucial role in potassium absorption and transportation. Here we report the isolation and characterization of a HKT1 homolog from C3 halophyte Suaeda salsa (L.) (SsHKT1), particularly under low K+ treatment. The SsHKT1 cDNA was 2033 nucleotides long including 1650 bp ORF for a 550 amino acids peptide and a predicted molecular mass of 63.0 kDa. The deduced amino acid sequence of SsHKT1 was 39-64% identical to other plant HKT-like sequences. A SsHKT1-specific antibody was prepared and reacted with a 63.0 kDa protein from S. salsa plasma membrane. Reverse transcriptase-PCR analysis showed that SsHKT1 was mainly expressed in leaf tissues and to a lesser extent, in root tissues. Amounts of SsHKT1 transcript were developmentally controlled and significantly up-regulated by K+ deprivation and NaCl treatment. The results suggested that SsHKT1 might play an important role in ion homeostasis and salt tolerance of S. salsa. PMID- 17852353 TI - Cloning and characterization of a cDNA encoding 14-3-3 protein with leaf and stem specific expression from wheat. AB - The 14-3-3 proteins, originally described as the mammalian brain proteins, are ubiquitous eukaryotic proteins and have been shown to exert an array of function. A great number of 14-3-3 sequences have been reported in Eudicotyledon. The data of 14-3-3 from the monocotyledon plants, however, are limited. In this report, a 14-3-3 cDNA (designated as Ta14A) was isolated from wheat. An extensive search in GenBank database revealed another 14 14-3-3 isoforms from monocotyledonous plants. These proteins plus 14-3-3 isoforms from Arabidopsis were used for phylogenetic reconstruction, which revealed two groups of 14-3-3 proteins in monocotyledonous plants, namely epsilon and non-epsilon, respectively. The epsilon isoforms were present in monocotyledonous plants. Therefore, the gene duplication to result in an epsilon and non-epsilon isoforms was likely to take place before the speciation of monocotyledon and Eudicotyledon plants. Structural analysis indicated that the different conserved domains and structural characters existed in the monocotyledon 14-3-3 isoforms, which will affect their interaction with other effector proteins. Ta14A was strongly expressed in leaf and stem, undetected in root, suggesting it may have the unique functions within these tissues. These data suggest that structure difference and spatial expression of 14-3-3 will be the important factors to confine its functional specificity. PMID- 17852354 TI - Comparison of promoter regions of SOX3, SOX14 and SOX18 orthologs in mammals. AB - SOX proteins constitute a large family of diverse and well conserved transcription factors implicated in the control of various developmental processes. Previously we have cloned and characterized human SOX3, SOX14 and SOX18 genes and performed functional characterization of their promoter regions. To better understand organization and function of SOX3, SOX14 and SOX18 promoters and to determine evolutionary conserved regulatory regions, we performed comparative genomic analyses of orthologous genes promoters. Mammalian orthologs of the human SOX3, SOX14 and SOX18 genes show high sequence identity in their promoter regions, particularly within basal promoters of the respective human genes. Binding sites for transcription factors NF-Y, Sp1 and USF1, previously shown to play critical roles in transcriptional regulation of these human genes, are highly conserved in sequence and position among diverse mammalian species. Conservation of binding sites might indicate their highly significant roles in maintaining the transcriptional regulation of these genes among different species. PMID- 17852355 TI - Molecular cloning and characterization of a novel H+-translocating pyrophosphatase gene in Zea mays. AB - A cDNA encoding a putative H+-translocating pyrophosphatase (H+-PPase) has been cloned from Zea mays by suppression subtractive hybridization (SSH) coupled with in silico cloning approach. The isolated 2974 bp full-length cDNA named ZmGPP contains a single 2400 bp open reading frame encoding a putative protein of 799 amino acids. The predicted protein has 16 transmembrane domains and is significantly similar to Golgi apparatus resident type-II H+-PPase from Arabidopsis thaliana. DNA gel blotting analysis shows that ZmGPP is a low-copy gene. Organ expression pattern analysis reveals that ZmGPPexpressed highly in leaf and tassel, followed by in stem, root, and ear. The Real-time RT-PCR assays showed that the expression of ZmGPP was up-regulated both in shoots and roots of maize seedlings under dehydration, cold and high salt stresses. Those results suggest that the ZmGPP product may play an important role in abiotic stress tolerance of Z. mays. PMID- 17852356 TI - Cloning and functional analysis of the swine eNOS promoter. AB - We have cloned the swine eNOS promoter and analyzed its function in newborn swine pulmonary artery endothelial cells (PAECs). Analysis of the 2.1 kb 5' flanking region revealed that the swine eNOS promoter is, like its counterparts in human and other species, a TATA-less promoter. The transcription start site, determined by 5' RLM-RACE, was located 62 bp upstream of the translation start codon. Promoter activity was demonstrated by transient transfection of 5' deletion promoter/luciferase constructs into swine PAECs, and indicated that the proximal region from -227 to -82 was necessary for basal promoter activity. Positive cis regulatory elements were present from -227 to -1290, while negative cis regulatory elements may be present from -1290 to -1926 bp. Electrophoretic mobility shift assay (EMSA) of the proximal region demonstrated that multiprotein complexes were formed in the conserved proximal region of the swine eNOS promoter and a novel Spl site at -68/-59 was involved in the formation of these complexes. PMID- 17852357 TI - Sequence analysis and characterization of vacuolar-type H+ -ATPase proteolipid transcript from Acanthus ebracteatus Vah1. AB - The vacuolar-type H+ -ATPase (V-ATPase) is a multimeric enzyme with diverse functions in plants such as nutrient transport, flowering, stress tolerance, guard cell movement and development. A partial sequence of V-ATPase proteolipid was identified among the expressed sequence tags (ESTs) generated from Acanthus ebracteatus, and selected for full-length sequencing. The 876-nucleotide cDNA consists of an open reading frame of 165 amino acids. The deduced amino acid sequence displays high similarity (81%) with its homologs from Arabidopsis thaliana, Avecinnia marina and Gossypium hirsutum with the four transmembrane domains characteristics of the 16 kDa proteolipid subunit c of V-ATPase well conserved in this protein. Southern analysis revealed the existence of several members of proteolipid subunit c of V-ATPase in A. ebracteatus. The mRNA of this gene was detected in leaf, floral, stem and root tissues, however, the expression level was lower in stem and root tissues. PMID- 17852358 TI - Molecular characterization of myostatin in black seabream, Acanthopagrus schlegelii. AB - Myostatin is a negative regulator of skeletal muscle growth and has a potential application in aquaculture. The black seabream myostatin gene was cloned and sequenced. It had three exons encoding a protein of 382 amino acids. A 90 bp 5' untranslated region (UTR) and a 536 bp 3'-UTR were obtained by RACE. Four microsatellite sequences, a (CAG)9, a (TC)12, a (CA)16 repeat and an "imperfect" (CA)25 microsatellite, were found in the myostatin. Two introns were 329 and 742 bp in length, respectively. The deduced amino acid sequence of the myostatin had a putative amino terminal signal sequence, a TGF-beta propeptide domain, a RXXR proteolytic processing site, a TGF-beta domain, and 12 conserved cysteine residues. The myostatin gene was expressed in four of the examined ten tissues and organs. The expression of myostatin was the strongest in the skeletal muscle and brain, intermediate in the eye, and low in the heart. PMID- 17852359 TI - Cloning and characterization of a novel human SPRYD4 gene encoding a putative SPRY domain-containing protein. AB - We report here the cloning and characterization of a novel human SPRYD4 gene which encodes a SPRY domain containing protein. The SPRYD4 gene is isolated from the human brain cDNA library, and mapped to 12q13.2 by searching the UCSC genomic database. The SPRYD4 cDNA is 1201 base pairs in length and contains an open reading frame encoding 207 amino acids. The SPRYD4 gene consists of two exons and encodes a putative protein with a SPRY domain ranging from 86 to 203 amino acids. The RT-PCR analysis reveals that SPRYD4 is ubiquitously expressed in 18 human tissues. However, it is strongly expressed in kidney, bladder, brain, thymus and stomach, while weakly expressed liver, testis, uterus, spleen and lung. Subcellular localization demonstrates that SPRYD4 protein is localized in the nuclear when overexpressed in COS-7 cell. PMID- 17852360 TI - 1A and 3D gene sequences of coxsackievirus B3 strain CC: variation and phylogenetic analysis. AB - Coxsackievirus B3 (CVB3) was thought to be the most common causative agent of life-threatening viral myocarditis. Coxsackievirus B3 strain CC (CVB3-CC) was isolated in China; however, no sequence data are available. The 1A and 3D regions of CVB3-CC were sequenced and phylogenetic analysis was done with reference to ten other CVB3 strains and all 36 prototype strains of human enterovirus B (HEV B). Sequence analysis showed that the 1A gene region of CVB3-CC consisted of 207 nucleotides, encoding 69 amino acids; and the 3D gene region was comprised of 1386 nucleotides, encoding 462 amino acids. Variation analysis showed that the 3D gene of CVB3 strain CC varied the least among the two regions. Phylogenetic tree analysis of the 1A and 3D regions indicated that CVB3-CC clustered together with CVB3 Nancy strain suggesting that there may be a close evolutionary relationship between the two strains. Incongruity was observed between the non-structural protein gene and the structural protein gene trees, according to the topological structure, indicating that recombination was occurred among these strains. PMID- 17852362 TI - Cloning and characterization of a novel PI-like MADS-box gene in Phalaenopsis orchid. AB - The specification of floral organ identity during development depends on the function of a limited number of homeotic genes, which are grouped into three classes. Most of these genes belong to the MADS-box gene family. The PISTILLATA (PI) family of MADS-box genes plays important roles in controlling the development of the petal and stamen of flowering plants. In an attempt to understand the molecular mechanisms behind floral development in the orchid, a MADS-box gene, PhPI10 was cloned from Phalaenopsis orchid. We provide phylogenetic evidence that PhPI10 is closely related to PI-like genes of angiosperms, which are required for establishing petal and stamen identity. In addition, there is a PI-motif in the C-terminal of the putative amino acid sequence of PhPI10. Southern analysis showed that a single copy of PhPI10 was present in the Phalaenopsis orchid genome. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that its transcription was only detectable in the top of the floral bud and undetectable in other vegetative organs. In the floral organs its expression was limited to the lip of the Phalaenopsis flower. PMID- 17852363 TI - Chitosan microparticles as oral delivery system for tetanus toxoid. AB - Systemic and local immune response against Chitosan encapsulated tetanus toxoid (CS-TT) microparticles is studied, prepared by ionic cross-linking using Sodium Tripolyphosphate (STPP). Final formulation was evaluated in terms of release of TT in 0.1 N HCl and PBS (pH 7.4), sedimentation profile and stability. CS-TT microparticles, TT in PBS and plain CS microparticles were orally administered to mice and TT (adsorbed) was administered through intramuscular route. Sera were analyzed for anti-TT IgG and intestinal lavage, faeces, intestinal washings for anti-TT IgA levels using an ELISA. Entrapment efficiency of about 100% was obtained. A dose dependent immune response was observed in mice vaccinated with Chitosan-TT microparticles. A strong enhancement of the systemic and local immune response against TT were found when compared with oral feeding of TT in PBS. The study shows the efficacy of chitosan microparticle suspension system, containing a high molecular protein (TT), in inducing the IgA in intestine and IgG in systemic circulation. This demonstrates that chitosan microparticles can prove to be a promising oral vaccine delivery system for mucosal and systemic immunity. PMID- 17852364 TI - Ocular permeability of pirenzepine hydrochloride enhanced by methoxy poly(ethylene glycol)-poly(D, L-lactide) block copolymer. AB - Methoxy poly(ethylene glycol)-poly(D, L-lactide) block copolymer was tested as an ocular permeation enhancer for pirenzepine hydrochloride. The block copolymers with the methoxy poly(ethylene glycol) to poly(D, L-lactide) weight ratio of 80/20, 50/50, 40/60 were synthesized by a ring-opening polymerization procedure. In vitro transcorneal experiments demonstrated that the block copolymer 80/20 significantly enhanced the transcorneal permeation of pirenzepine at the mass ratio of 1/1.4 (pirenzepine hydrochloride/copolymer). Interaction between pirenzepine and copolymer was identified by infrared spectroscopy analysis and dialysis experiments. Ocular pharmacokinetics of pirenzepine/copolymer preparation by in vivo instillation experiments confirmed that block copolymer could enhance the ocular penetration of pirenzepine. Ocular chronic toxicity experiments of block copolymer and pirenzepine/copolymer preparation were studied on rabbits, and no significant toxicity in both groups was observed within 9 months. It could conclude that pirenzepine/copolymer preparation is effective and safe in ocular delivery of pirenzepine. PMID- 17852365 TI - The influence of formulation factors on the kinetic release of metoprolol tartrate from prolong release coated minitablets. AB - The aim of this work was to study the possibility to obtain an oral extended release dosage forms with zero order kinetic release by coating minitablets (containing metoprolol tartrate) with insoluble methacrylate film coating (Eudragit NE 40D) in a fluidized bed system. To achieve this aim a full factorial experimental design with two factors and three levels was used in order to study de influence of the amount of polymer film formatting (Eudragit NE 40D) and the amount of pore generating excipient in polymeric insoluble film (low viscosity hydroxypropyl methylcellulose-Methocel E 15LV) on the in vitro drug release profile. PMID- 17852366 TI - The influence of content, task and sensory interaction on multimedia quality perception. AB - Human sensory interaction plays an important (but not yet fully understood) role in determining how individuals interact with the world around them. There are numerous types of sensory interaction and this paper examines the interaction of the auditory and visual senses for viewers of multimedia systems. This paper addresses two questions: first, does perception of quality in one modality affect the perception of quality in the other modality and, second, does focusing attention towards one modality affect the viewer's ability to detect errors in the other modality? The perception of audio quality and video quality are closely linked for certain multimedia content. To investigate this relationship, two experiments were conducted where participants were presented with multimedia content where varying distortion had been introduced into both the auditory and visual streams. Participants were asked to state their opinion of the audio, video or overall quality using a standardized scale. Results and subsequent statistical analysis showed that subjective audio quality varied with the video quality and vice versa. Furthermore, when a participant was attending to just one modality, they were less sensitive to reduced quality in the other modality. PMID- 17852367 TI - Perceived competence in computer use as a moderator of musculoskeletal strain in VDU work: an ergonomics intervention case. AB - Musculoskeletal strain and other symptoms are common in visual display unit (VDU) work. Psychosocial factors are closely related to the outcome and experience of musculoskeletal strain. The user-computer relationship from the viewpoint of the quality of perceived competence in computer use was assessed as a psychosocial stress indicator. It was assumed that the perceived competence in computer use moderates the experience of musculoskeletal strain and the success of the ergonomics intervention. The participants (n = 124, female 58%, male 42%) worked with VDU for more than 4 h per week. They took part in an ergonomics intervention and were allocated into three groups: intensive; education; and reference group. Musculoskeletal strain, the level of ergonomics of the workstation assessed by the experts in ergonomics and amount of VDU work were estimated at the baseline and at the 10-month follow-up. Age, gender and the perceived competence in computer use were assessed at the baseline. The perceived competence in computer use predicted strain in the upper and the lower part of the body at the follow up. The interaction effect shows that the intensive ergonomics intervention procedure was the most effective among participants with high perceived competence. The interpretation of the results was that an anxiety-provoking and stressful user-computer relationship prevented the participants from being motivated and from learning in the ergonomics intervention. In the intervention it is important to increase the computer competence along with the improvements of physical workstation and work organization. PMID- 17852361 TI - Initial analysis of tandemly repetitive sequences in the genome of Zhikong scallop (Chlamys farreri Jones et Preston). AB - Tandemly repetitive sequences are widespread in all eukaryotic genomes, but data on tandem repeats are limited in Zhikong scallop (Chlamys farreri). In the present study, paired-end sequencing of 2016 individual fosmid clones resulted in 3646 sequences. A total of 2,286,986 bp of genomic sequences were generated, representing approximately 1.84 per thousand of the Zhikong scallop genome. Using tandem repeats finder (TRF) software, a total of 2500 tandem repeats were found, including 313 satellites, 1816 minisatellites and 371 microsatellites. The cumulative length of tandem repeats was 552,558 bp, accounting for 24.16% of total length. Specifically, the length of microsatellites, minisatellites and satellites was 9425, 336,001 and 207,132 bp, accounting for 1.71, 60.81 and 37.49% of the length of tandem repeats, and 0.41, 14.69 and 9.06% of total length, respectively. The detailed information on the characteristic of all repeat units was also represented, which will provide a useful resource for physical mapping and better utilization of the existing genomic information in Zhikong scallop. PMID- 17852368 TI - Ready steady push--a study of the role of arm posture in manual exertions. AB - This study investigated arm posture and hand forces during bi-manual pushing. Nine male and eight female participants performed isometric exertions at two reach distances (0 and elbow-grip) and six different positions of the hand interface (handle), defined by the plane (longitudinal, lateral, horizontal) and orientation (0 degrees and 45 degrees). Electrogoniometer instruments were used to measure the displacements/postures of the wrist and elbow joints and the forearm, and force measuring strain gauges were used to measure the exerted hand forces (x-, y- and z-components). The results showed that ability to vary arm posture, particularly the forearm, is important during build up of force and that people tend to seek for a balance in the forces applied at the hands by exerting more in the vertical direction. Also, lateral plane handle positions permitted exertion of greater forces than longitudinal and horizontal plane positions. PMID- 17852369 TI - Ergonomics evaluation of Picture Archiving and Communication System implementations in two X-ray departments. AB - Two large X-ray departments in the County of Stockholm have changed from traditional analogue technology to digital imaging, including the implementation of Picture Archiving and Communication Systems (PACS). One of the departments was moved to a completely new purpose-built building and equipped with the latest technology, but for the other one the change merely meant rebuilding and adaptation of existing rooms on the premises. The objectives of the present study were to evaluate the ergonomics effects of the new technique in the two X-ray departments and to find out whether the implementation of digital imaging technique came up to expectations of improved ergonomics and work environment. Another purpose was to compare the outcomes for the two departments, in order to learn about the importance of the different implementation approaches. Questionnaires were sent out to the two departments both before the implementation of PACS and after the transition. The questionnaires covered several aspects of work conditions, such as working time, the physical and psychosocial environment, physical work load and musculoskeletal complaints, expectations from the digital technology, etc. The changeover went better than expected and even high expectations were fulfilled and surpassed. However, there were also some unexpected and distressing results; for example, a substantial increase in headaches and musculoskeletal symptoms as well as the use of pain killers among the radiologists of one of the X-ray departments. PMID- 17852370 TI - The effects of sensory impairments on product experience and personal well-being. AB - To determine the roles that the sensory modalities play in user product interactions, one modality was blocked during the execution of eight simple tasks. Participants reported how they experienced the products and how they felt during the experiment. Blocking vision resulted in the largest loss of functional information, increased task difficulty and task duration, and fostered dependency. On the other hand, the other senses were used more and product experiences increased in perceived intenseness. When touch was blocked, the perceived loss of information was smaller and participants reported that familiar products felt less like their own. Blocking audition resulted in communication problems and a feeling of being cut off. Blocking olfaction mainly decreased the intenseness of the experience. These outcomes suggest that vision mainly plays a functional role in everyday user-product interactions, whereas the main role for olfaction lies in the affective domain. Sensory impairments change the way people experience products. Blocking a single modality during everyday tasks gives insight into the impact of impairments. These insights can be used to develop products for multiple user groups (inclusive design) or products used under extreme environmental conditions. PMID- 17852371 TI - Perception and biomechanics data in a manual handling task: a comparative study. AB - This paper explores the use of subjective perception tasks and its correlations with biomechanical data in the evaluation of manual material handling. Three main dimensions were considered for perception: physical regroups sensations issued from a specific body area; operative regroups feelings related to the execution of the task; and performance regroups feelings that involve a judgement on the execution or reflect overall sensations. The following questions were then explored. To what extent are perception data related to biomechanics data? Do both approaches lead to similar conclusions or interpretations when effect of practice, format and off-centre were tested? How can they complement one another? The task consisted of transferring 50 series of three 15 kg loads in order to verify the impact of free practice, format (box/cylinder) and load centre of gravity position. Eleven subjects rated perception on a CR-10 scale (Borg 1982) after each series. The session was completed with an interview on perception. The net resulting moment was systematically found to be the best correlated with data perception. While all physical and performance items corresponded in various ways to biomechanics data, perceptions associated with operative dimension appeared to be less related with biomechanical data. As regards the impact of practice, format and off-centre, both approaches would lead to the same conclusions, except for the effect of the off-centre. Verbal data add rational information about how or why perception can or cannot be reflected in biomechanics data. How both approaches can be matched more closely in manual handling is discussed. PMID- 17852372 TI - The effects of prior warning and lifting-induced fatigue on trunk muscle and postural responses to sudden loading during manual handling. AB - This study investigated the effects of warning and lifting-induced fatigue on trunk muscle activity and postural responses to sudden loading. Thirty-one male subjects were subjected to sudden loading of a hand-held box with and without prior warning, before and after either lifting-induced fatigue or light callisthenic exercises. Results showed that warning did not alter the level of trunk muscle activity prior to sudden loading. Following warning, there was a reduction in all muscle and joint onset latencies and the magnitude of hip and knee flexion. Although fatigue did not influence muscle and joint initiation, it did negate the effects that warning had on reducing joint displacement. These findings indicate that warning prior to sudden loading may enhance postural responses, reduce ranges of joint motion and increase stability. However, the benefits of prior warning for reducing ranges of joint motion may not be present when a person is fatigued. Sudden unexpected loading and fatigue arising from manual handling practices in the workplace have been identified as contributing factors to the risk of low back injury. Findings from this study provide information that is important for the design of interventions intended to reduce the incidence of manual handling-related back injuries. PMID- 17852374 TI - Distribution and determinants of maximal physical work capacity of Korean male metal workers. AB - The distribution of maximal physical work capacity (MPWC) can be used to establish an upper limit for energy expenditure during work (EEwork). If physically demanding work has wearing effects, there will be a negative relationship between MPWC and workload. This study was conducted to investigate the distribution of MPWC among Korean metal workers and to examine the relationship between workload and MPWC. MPWC was estimated with a bicycle ergometer using a submaximal test. Energy expenditure was estimated by measuring heart rates during work. The study subjects were 507 male employees from several metal industries in Korea. They had a lower absolute VO2max than the Caucasian populations described in previous studies. The older workers had a lower physical capacity and a greater overload at work. A negative relationship was found between MPWC and workload across all age groups. Upper limits for EEwork for all age groups and for older age groups are recommended based on the 5th percentile value of MPWC. PMID- 17852373 TI - Two posture analysis approaches and their application in a modified rapid upper limb assessment evaluation. AB - This paper presents two posture risk quantification methods: first, an event based method where the most common and the worst postures are estimated in a task; second, a time-based method where posture distributions are calculated from random samples of observed postures in the task. A 'click-on-screen' posture data entry method was developed for the time-based posture analysis method to make the observation process easier and to reduce possible posture categorization bias. Both methods were used to quantify various work posture parameters among a study cohort of 733 subjects from a prospective epidemiological study of upper extremity musculoskeletal disorders. Composite posture indices using a modified Rapid Upper Limb Assessment (RULA) method were also computed using data obtained by the two posture analysis methods. Results showed that both methods were able to distinguish jobs with large differences in certain posture measures. However, they did not produce the same results and could not be used interchangeably. Risk evaluation criteria should be developed, either for specific posture parameters or as a composite index, with a well-defined postural analysis method, so that users can follow exact procedures and obtain comparable results. The event-based method is easy to use and may suit practitioners better, while the time-based method adds more information to the measurement and may suit users who want more detailed information about posture exposure. PMID- 17852375 TI - Estimation of compressive forces on lumbar spine from categorical posture data. AB - To combine estimates of trunk posture and force into an integrated measure of load on the low back, continuous variables for body angles were estimated by assuming specified distributions within corresponding posture categories with Monte-Carlo (MC) simulation. The estimated posture angles were compared with reference measurements from the Lumbar Motion Monitor and inclinometers. The lumbar compression estimates, generated from simulated posture angles and from direct measurement, were compared. Trunk flexion showed high correlation between direct measurements and simulated angles, as did L5/S1 compression. The MC approach to extracting continuous posture angles from categorized observations did not appear to introduce large error in the variables used to estimate spinal compressive forces. When instrumentation methods of postural assessment are not feasible, a simulation approach combined with biomechanical modelling could be used to integrate multiple external exposure variables into estimates of compressive forces acting on the low back. PMID- 17852376 TI - A biomechanical analysis of anterior load carriage. AB - Front load carriage is a common occupational task in some industries (e.g. agriculture, construction), but, as compared to lifting tasks, relatively little research has been conducted on the biomechanical loading during these activities. The focus of this study was to explore the low back biomechanics during these activities and, specifically, to examine the effects of load height and walking speed on trunk muscle activity and trunk posture. Eleven male participants participated in two separate front load-carriage experiments. The first experiment called for carrying a barbell (with weight corresponding to 20% of elbow flexion strength) at three heights (knuckle height, elbow height and shoulder height) at a constant horizontal distance from the spine. The second experiment called for participants to carry a bucket of potatoes weighing 14 kg at the same three heights, but with no further restrictions in technique. In both experiments, the participants performed this task while either standing still or walking at a self-selected speed. As they performed these tasks, the activity levels of the right-side muscle of the rectus abdominis, external oblique, biceps brachii, anterior deltoid and three levels (T9, T12 and L3) of the erector spinae were sampled. Mid-sagittal plane trunk posture was also quantified using three magnetic field-based motion sensors at T9, T12 and L3. The results showed a significant effect of both walking speed and load height on trunk posture and trunk muscle activity levels in both the barbell and bucket experiments. In the barbell experiment, the walking trials generated 43% more trunk muscle activity than the standing trials. Trials at shoulder height produced 11% more muscle activity than trials at elbow height in the T9 erector spinae muscles and 71% more muscle activity in the anterior deltoid. In the bucket experiment, trunk muscle activity responded in a similar fashion, but the key result here was the quantification of the natural hyperextension posture of the spine used to balance the bucket of potatoes. These results provide insight into muscle activation patterns in dynamic settings, especially (load) carrying biomechanics, and have implications in industrial settings that require workers to carry loads in front of their bodies. PMID- 17852377 TI - The effects of multifocal refractive lenses on occipital extension and forward head posture during a visual task. AB - The purpose of this study was to determine if a change in forward head posture and occipital extension occurred in participants who wore multifocal lenses vs. those persons with non-multifocal lenses while performing an 8-min visual reading task on a visual display unit (VDU). Forty-two healthy human participants were recruited for this study. Thirty-three participants completed the study. Fourteen participants wore multifocal lenses and 19 wore frames with non-multifocal lenses. To evaluate the degree of change of forward head posture and occipital extension digital photographs of cervical posture were taken at four different time intervals: prior to performing the reading task and at 3, 5 and 8 min during the reading task. The digital photographs were analysed utilizing a computer program. Two one-way ANOVA were utilized to determine the degree of change of forward head posture and occipital extension between groups. A significant difference was identified between groups for changes in degrees of forward head posture while performing a visual reading task on a VDU. However, no significant difference between groups was found for occipital extension while performing the same task. Multifocal wearers exhibit greater degrees of change in forward head posture and occipital extension than non-multifocal wearers. These postural changes may place them at a greater risk for musculoskeletal disorders and headaches. PMID- 17852378 TI - Stress-induced muscle effort as a cause of repetitive strain injury? AB - The influence of stress-induced muscle effort during computer utilization was tested in patients with repetitive strain injury (RSI). Twenty academic researchers with a formal medical diagnosis of RSI and 20 matched controls, randomly selected from a sample of 71 colleagues with and without RSI, typed after stress (induced via an intelligence/skill task under social pressure) and after relaxation. Results indicated that both groups had more electromyography (EMG) activity in the shoulder muscles during typing after stress than after relaxation, but that patients started with higher baseline muscle activity. Furthermore, EMG activity of different muscle groups during typing after stress correlated among controls, but not among patients. Finally, analysis of intake forms showed that patients scored higher than controls on neuroticism and alexithymia, but not on extraversion, openness, agreeableness and conscientiousness. It was concluded that deviations in muscle activity during computer utilization, as well as neuroticism and alexithymia, may be risk factors for RSI. PMID- 17852379 TI - Detection of dehydroepiandrosterone and androsterone in a traditional Chinese herbal product. AB - Dehydroepiandrosterone (DHEA) and androsterone (ADT) were detected in a traditional Chinese herbal product by gas chromatography-mass spectrometry (GC MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS). DHEA and ADT were tentatively identified by comparing their electron ionization (EI) mass spectra with those in the GC-MS Wiley database. A multiple reaction monitoring (MRM) scan was performed in LC-MS/MS to confirm the presence of the DHEA and ADT in the herbal product extract. Both the [M + H]+ and the [M + NH4]+ of DHEA and ADT were selected as the precursor ions. DHEA was detected with ion transitions m/z 306.4 --> 271.2, 306.4 --> 253.3, 289.2 --> 270.9, 289.3 --> 253.1 while ADT was detected with ion transitions m/z 308.5 --> 273.6, 308.5 --> 255.3, 291.5 --> 273.5, 291.5 --> 255.2, which confirmed the presence of the two steroid hormones in the herbal product. Limits of detection (LODs) of 0.2 microg ml(-1) for DHEA and 0.3 microg ml(-1) for ADT were found in methanolic standard solutions when [M +NH4]+ of DHEA and ADT were selected as the precursor ions, which allowed the detection of DHEA and ADT at trace level without time-consuming derivatization. PMID- 17852380 TI - Biodiversity of Aspergillus section Flavi in the United States: a review. AB - Fungi belonging to Aspergillus section Flavi are of great economic importance in the United States due to their ability to produce toxic and carcinogenic aflatoxins in agricultural commodities. Development of control strategies against A. flavus and A. parasiticus, the major aflatoxin-producing species, is dependent upon a basic understanding of their diversity in agricultural ecosystems. This review summarizes our current knowledge of species and population diversity in the United States in relation to morphology, mycotoxin production and genetic characters. The high genetic diversity in populations of aflatoxigenic fungi is a reflection of their versatile habits in nature, which include saprotrophic colonization of plant debris in soil and parasitism of seeds and grain. Genetic variation within populations may originate from a cryptic sexual state. The advent of intensive monoculture agriculture not only increases population size but also may introduce positive selective pressure for aflatoxin production due to its link with pathogenicity in crops. Important goals in population research are to determine how section Flavi diversity in agricultural ecosystems is changing and to measure the direction of this evolution. PMID- 17852381 TI - Levels of eight trace elements in edible mushrooms from a rural area. AB - Eight trace elements were determined using ICP-MS in 78 fruiting body samples of 22 edible mushroom species. The mushrooms were collected from four sites in a rural area, unpolluted by human activity. Median values (dry matter) were as follows: Arsenic (As) 1.45 mg kg(-1), barium (Ba) 1.41 mg kg(-1), cobalt (Co) 0.28 mg kg(-1), copper (Cu) 47.0 mg kg(-1), rubidium (Rb) 130 mg kg(-1), silver (Ag) 2.95 mg kg(-1), thallium (Tl) 0.02 mg kg(-1) and vanadium (V) 0.25 mg kg( 1). Higher trace element accumulation was observed in samples of Macrolepiota procera, Macrolepiota rhacodes, Lycoperdon perlatum, Lycoperdon gigantea and Xerocomus chrysenteron for As and Cu, and in samples of Cantharellus cibarius and of genera Boletus and Suillus for Rb. PMID- 17852382 TI - FTIR-ATR infrared spectroscopy for the detection of ochratoxin A in dried vine fruit. AB - A method of screening sultanas for ochratoxin A (OTA) contamination, using mid infrared spectroscopy/Golden Gate single-reflection ATR (attenuated total reflection), is described. The main spectral characteristics of sultanas from different sources were identified in a preliminary acquisition and spectral analysis study. Principal component analysis (PCA) showed that samples of various origins had different spectral characteristics, especially in water content and the fingerprint region. A lack of reproducibility was observed in the spectra acquired on different days. However, spectral repeatability was greatly improved when water activity of the sample was set at 0.62. A calibration curve of OTA was constructed in the range 10-40 microg OTA kg(-1). Samples with OTA levels higher than 20 microg kg(-1) were separated from samples contaminated with a lower concentration (10 microg OTA kg(-1)) and from uncontaminated samples. The reported methodology is a reliable and simple technique for screening dried vine fruit for OTA. PMID- 17852383 TI - Contribution of water and cooked rice to an estimation of the dietary intake of inorganic arsenic in a rural village of West Bengal, India. AB - Arsenic contamination of rice plants by arsenic-polluted irrigation groundwater could result in high arsenic concentrations in cooked rice. The main objective of the study was to estimate the total and inorganic arsenic intakes in a rural population of West Bengal, India, through both drinking water and cooked rice. Simulated cooking of rice with different levels of arsenic species in the cooking water was carried out. The presence of arsenic in the cooking water was provided by four arsenic species (arsenite, arsenate, methylarsonate or dimethylarsinate) and at three total arsenic concentrations (50, 250 or 500 microg l(-1)). The results show that the arsenic concentration in cooked rice is always higher than that in raw rice and range from 227 to 1642 microg kg(-1). The cooking process did not change the arsenic speciation in rice. Cooked rice contributed a mean of 41% to the daily intake of inorganic arsenic. The daily inorganic arsenic intakes for water plus rice were 229, 1024 and 2000 microg day(-1) for initial arsenic concentrations in the cooking water of 50, 250 and 500 microg arsenic l(-1), respectively, compared with the tolerable daily intake which is 150 microg day( 1). PMID- 17852384 TI - Mercury in fish: concentration vs. fish size and estimates of mercury intake. AB - Total mercury concentrations were determined in different fish size classes of commercial importance such as, conger eel (Conger conger), starry ray (Raja asterias), forkbeard (Phycis blennoides), frostfish (Lepidopus caudatus), striped mullet (Mullus barbatus), red gurnard (Aspitrigla cuculus) and yellow gurnard (Trigla lucerna) in order to evaluate variations in consumer exposure to mercury as a function of fish consumption of a spectrum of different sizes. The highest mean levels of total mercury were detected in conger eel (0.80 microg g(-1)) and starry ray (0.75 microg g(-1)). Forkbeard (0.67 microg g(-1)), frostfish (0.59 microg g(-1)) and striped mullet (0.55 microg g(-1)) showed slightly lower levels, while red gurnard (0.33 microg g(-1)) and yellow gurnard (0.22 microg g( 1)) exhibited the lowest concentrations. The results of linear regression analysis showed a significant relationship between mercury concentrations and fish size for all species. Consequently, dietary consumption of larger size specimens leads to an increase in the exposure level for consumers. Understanding by consumers of all factors leading to an increase of exposure to mercury is the first step to enable them to make decisions about eating fish. PMID- 17852385 TI - Sorption of aroma compounds in PET and PVC during the storage of a strawberry syrup. AB - The sorption of 14 aroma compounds into PET and PVC was monitored during storage of a strawberry syrup for 1 year. Concentrations in the syrup and in the polymer were determined during storage and compared with previously published results obtained with glass bottles. Apparent partition coefficients between the polymer and the syrup (noted K app) were estimated from experimental kinetics without reaching equilibrium K app values and optimally identified from the kinetic data obtained between 30 and 90 days. They exhibited a similar behaviour for both polymers with values were between 2 x 10(-5) and 2 x 10(-3), 4 x 10(-5) and 3 x 10(-2), respectively, for PET and PVC. The variation of K app values in PET was mainly correlated to the polarity of tested compounds as assessed by their log P values. By contrast, the variations in K app values for PVC were mainly related to their chain lengths. Due to slightly higher partition coefficients and diffusion coefficients in PVC compared with PET, the amount of absorbed aroma was four times higher in PVC than in PET; however, the amount of absorbed aroma compounds was less than 0.1% of the initial amount present into the syrup, except for octyl butanoate. The variation in concentration in the syrup was interpreted as a combination of a degradation process and a transport process into the packaging material. Both effects were particularly noticeable for both PET and unstable aroma compounds. PMID- 17852386 TI - Trace analysis of perchlorate anion in selected food products by reverse-phase liquid chromatography-tandem mass spectrometry. AB - An alternative, rapid, and reproducible method of analysis for perchlorate in selected food products (fruit and vegetable juice, milk, and bottled water) was developed and validated. Improvements over previous methods were achieved by the use of a rugged and inexpensive C18 column, a multi-mode OASIS HLB solid-phase extraction cartridge for sample clean-up, and acetic acid for pH adjustment and protein precipitation. The hydrophobicity of the perchlorate anion gives it good retention and separation characteristics on C18 chromatographic columns. The C18 column allowed for the use of 90% of acetonitrile at a low flow rate (0.3 ml min( 1)), without splitting, and could also be regenerated with organic solvents, unlike an ion-exchange column. Perchlorate levels in selected commercial food samples were: <1.0-2.1 ng g(-1) (fruit and vegetable juices, reported here for the first time), <1.0-5.0 ng g(-1) (milk), and <1.0 ng g(-1) (bottled water). PMID- 17852387 TI - Validation of an analytical method for the determination of carbadox and olaquindox in feedstuff by liquid chromatography coupled to UV and/or diode array detection. AB - The performance characteristics of an analytical method based on high-performance liquid chromatography (HPLC) for the detection of the banned growth promoters, carbadox and olaquindox, in feedstuff were determined via a collaborative study. The relative standard deviation of repeatability (RSDr) ranged 1.1-5.5% for carbadox and 2.5-6.2% for olaquindox. The relative standard deviation of reproducibility (RSDR) ranged 6.4-10.7% for carbadox and 12.8-20.0% for olaquindox. In all cases, the HORRAT values were equal or below the critical value of 1.5. Moreover, trueness in all cases was between the acceptance limits of 80 and 110%. Consequently, it was concluded that the method is suitable for quantitative evaluation. The method was also qualitatively assessed in terms of correct identification of the target analytes by examination of the UV spectrum when the more specific diode array detector was coupled to HPLC. In all cases, the percentage of correct identifications was >or=94% for olaquindox and carbadox, while the percentage of false negatives was 0.990), detection and quantification limits (between 0.001 and 0.1 microg g(-1) and between 0.005 and 0.5 microg g(-1), respectively), and precision (<19% at the quantification limits and from 6 to 14% at ten times higher concentrations). However, recoveries were not so good, ranging from 19 to 92%. Honey samples were found that were contaminated with bromophos ethyl, diazinon, fonofos, pirimiphos ethyl, pyrazophos, and temephos at estimated concentrations from 6.2 +/- 1.2 to 19 +/- 3 ng g(-1). PMID- 17852392 TI - NovaSil clay intervention in Ghanaians at high risk for aflatoxicosis. I. Study design and clinical outcomes. AB - A 3-month double-blind and placebo-controlled, phase IIa clinical trial was conducted in Ghana to investigate the safety, tolerance and aflatoxin-sorption efficacy of dietary NovaSil (NS). Volunteers (507 subjects) were clinically screened to evaluate their general health, pregnancy status and blood AFB(1) albumin adduct levels. Of these subjects, 177 were randomly assigned to three groups: high-dose (HD), low-dose (LD) and placebo-control (PL) groups receiving 3.0, 1.5 and 0 g NS day(-1) in capsules. Trained study-monitors supervised NS capsule administration to participants and recorded side-effects daily. Physical examinations were performed monthly. Blood and urine samples were collected for laboratory analysis. Approximately 92% of the participants (162 of 177) completed the study and compliance rate was over 97%. Overall, 99.5% of person x time reported no side-effects throughout the study. Mild to moderate health events ( approximately 0.5% of person x time) were recorded in some participants. Symptoms included nausea, diarrhea, heartburn and dizziness. These side-effects were statistically similar among all three groups. No significant differences were shown in hematology, liver and kidney function or electrolytes in the three groups. These findings demonstrate that NS clay is apparently safe and practical for the protection of humans against aflatoxins in populations at high risk for aflatoxicosis. PMID- 17852393 TI - Peanut and hazelnut traces in cookies and chocolates: relationship between analytical results and declaration of food allergens on product labels. AB - Accidental exposure to hazelnut or peanut constitutes a real threat to the health of allergic consumers. Correct information regarding food product ingredients is of paramount importance for the consumer, thereby reducing exposure to food allergens. In this study, 569 cookies and chocolates on the European market were purchased. All products were analysed to determine peanut and hazelnut content, allowing a comparison of the analytical results with information provided on the product label. Compared to cookies, chocolates are more likely to contain undeclared allergens, while, in both food categories, hazelnut traces were detected at higher frequencies than peanut. The presence of a precautionary label was found to be related to a higher frequency of positive test results. The majority of chocolates carrying a precautionary label tested positive for hazelnut, whereas peanut traces were not be detected in 75% of the cookies carrying a precautionary label. PMID- 17852394 TI - Fusarium toxins and total fungal biomass indicators in naturally contaminated wheat samples from north-eastern Poland in 2003. AB - Concentrations of fungal metabolites were measured in 32 wheat grain samples from north-eastern Poland in 2003. The samples originated from fields cultivated conventionally (but varying in chemical protection level) or cultivated organically. Concentrations of Fusarium toxins (HT-2, DON, 3-AcDON, NIV), trichodiene, microbial biomass indicators (fungal ergosterol and general adenosine 5'-triphosphate (ATP)) and seed vigour were assessed. A large variation between samples was observed, depending on their origin. Seed from organic farms contained similar amounts of Fusarium toxins but more ergosterol and ATP than conventionally grown and chemically protected seed. The highest levels of toxins and ergosterol were detected in samples from conventional cultivation lacking chemical protection. Intensive agronomic practices (including complete chemical protection) significantly lowered the levels of ergosterol, ATP and trichodiene, as compared with other cultivation systems. PMID- 17852395 TI - Solid-phase micro-extraction (SPME-GC) and sensors as rapid methods for monitoring lipid oxidation in nuts. AB - Dry foods with high fat content are susceptible to lipid oxidation, which involves a quality deterioration of the product, since this process is responsible for the generation of off-flavours. Hexanal is considered to be a good shelf-life indicator of such oxidation products. In addition, due to its high volatility, hexanal can be easily determined by fast headspace analytical techniques. For this reason an electronic nose comprising ten metal oxide semiconductors (MOS) and a solid-phase microextraction (SPME) coupled with gas chromatography and flame ionization detector (GC-FID) method were compared in order to determine hexanal formed in hazelnuts during storage under different conditions (room temperature, 40 degrees C, ultraviolet light, with and without oxygen scavenger). The results obtained by the two methods showed a good correlation, confirming the possibility of using a multi-sensor system as a screening tool for the monitoring of shelf-life and oxidation state of nuts. PMID- 17852396 TI - 4-hydroxy-2-alkenals in polyunsaturated fatty acids-fortified infant formulas and other commercial food products. AB - 4-Hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE) were determined using selected ion-monitoring gas chromatography-mass spectrometry (GC-MS) in 56 kinds of commercially available PUFA-fortified foods including infant formulas and baby foods. HHE and HNE, each specifically coming from the oxidation of n-3 and n-6 polyunsaturated fatty acids (PUFA), were observed at <10-77 and 41-132 microg kg( 1) in the infant formulas (n = 12) and at <10-52 and 36-116 microg kg(-1) in the baby foods (n = 7), respectively. 4-Hydroxy-2-alkenals in infant formulas and baby foods were further determined at 10 and 30 days after opening in an attempt to examine the time dependence of the levels of 4-hydroxy-2-alkenals. The values of HHE and HNE had increased appreciably to <10-220 and 79-792 microg kg(-1) in infant formulas and to <10-112 and 135-572 microg kg(-1) in baby foods, respectively, at 10 days and decreased, although statistically not significant, in most of the tested samples after 30 days, which suggested that the reactive compounds might interact with other constituents like proteins in the samples to form adducts or be decomposed with time. Based on the current study, it was calculated that 3-month to 1-year-old babies maintained exclusively on these commercially available PUFA-fortified infant formulas or baby foods could be exposed to a maximum of 20.2 microg kg(-1) body weight day(-1) of 4-hydroxy-2 alkenals, which is two orders of magnitude higher than the exposure of Korean adults estimated in a previous study of the authors' (2005). The present study may trigger future studies investigating the physiological influence of 4-hydroxy 2-alkenals originating from the diet on man at an early stage of development. PMID- 17852397 TI - Public information campaign on aflatoxin contamination of maize grains in market stores in Benin, Ghana and Togo. AB - Rotary International with the International Institute of Tropical Agriculture (IITA) conducted an information campaign from 2000 to 2004 to increase public awareness of aflatoxin in Benin, Ghana and Togo. Key informant interviews with 2416 respondents showed poor baseline knowledge of aflatoxin and its health risks. The campaign included monitoring of aflatoxin contamination in maize grains from market stores in 38 cities and towns. Aflatoxin concentration in contaminated samples ranged from 24 to 117.5 ng g(-1) in Benin, from 0.4 to 490.6 ng g(-1) in Ghana, and from 0.7 to 108.8 ng g(-1) in Togo. The campaign significantly increased public awareness that populations were exposed to high levels of aflatoxin. The number of maize traders who were informed about the toxin increased 10.3 and 3.2 times in Togo and Benin, respectively; at least 33% more traders believed the information in each of Benin and Togo; 11.4 and 28.4% more consumers sorted out and discarded bad grains in Benin and Ghana, respectively. This paper concludes that sustained public education can help reduce aflatoxin contamination. PMID- 17852398 TI - Toxic and essential metal concentrations in four tissues of red deer (Cervus elaphus) from Baranja, Croatia. AB - Kidney (n = 297), liver (n = 52), jawbone (n = 80) and muscle (n = 48) samples collected from red deer (Cervus elaphus) from north-eastern Croatia in the 2002- 05 hunting season were analysed for cadmium (Cd), copper (Cu), iron (Fe), mercury (Hg), lead (Pb), selenium (Se) and zinc (Zn) using atomic absorption spectrometry. Statistical evaluation of results showed age-related accumulations of renal cortex Cd and Zn, bone Pb, and muscle Zn. Renal cortex Cd and Zn were significantly associated. In addition, concentrations of Cd and Pb in muscle tissue were significantly correlated with Fe content. Found levels of toxic metals were not likely to affect the health status of animals. A total of 49% of the muscle, 60% of the kidney and 6% of the liver samples were unsuitable for human consumption according to Croatian regulations for Cd in food. However, the calculated intake of Cd through deer meat consumption is small and represents no health risk when consumption is moderate. PMID- 17852399 TI - Determination of ochratoxin A in grapes of Greek origin by immunoaffinity and high-performance liquid chromatography. AB - A simple analytical method for ochratoxin A (OTA) determination in grapes is described, using aqueous methanolic extraction, an immunoaffinity column clean-up step and high-performance liquid chromatography with fluorescence detection. Mean recovery was 94% (RSD = 4.0%) with a detection limit of 0.4 ng g(-1) and quantification limit of 1.20 ng g(-1). Repeatability (r) and reproducibility (R) were 1.17 and 1.34, respectively. OTA determinations were applied to 50 grape samples (23 different varieties) originating from representative regions of Greece. Results showed the presence of OTA in 86% of samples tested (n = 50). Traces were found in 56% of samples but OTA was not detectable in 14% of samples. Traces were also found in 4% of red, organically grown samples. The most contaminated were three samples of red grapes, two from Central Greece (2.69 and 1.41 ng g(-1)), both table and wine-making grapes. The third sample (1.46 ng g( 1)), originating from the island of Samos, was used only in wine-making. Mean (1.06 ng g(-1)) and median (0.76 ng g(-1)) OTA concentrations in red grapes were slightly higher compared to the mean (0.82 ng g(-1)) and median (0.65 ng g(-1)) concentrations in white grape samples. The study shows that the potential risk for a person of 60 kg ranged from 0.9 to 9 ng kg(-1) bw day(-1) and is dependent on the quantity of grapes consumed daily. PMID- 17852400 TI - Hair mercury levels in relation to fish consumption in a community of the Moroccan Mediterranean coast. AB - Coastal populations with high seafood consumption in the Mediterranean have a significant exposure to dietary methylmercury, and areas where environmental mercury pollution is an issue due to industrial activities are of special concern. The study was undertaken with the aim of assessing methylmercury exposure through fish consumption in a community of north Morocco and characterizing the relevant health risk. Concentrations of total mercury were determined in human hair, a biomarker of methylmercury exposure, and in locally consumed fish by cold vapour atomic absorption spectrophotometry. Based on consumption frequencies reported by the 108 subjects included in the study the weekly intake of methylmercury was estimated and biomarker data were evaluated in relation to the estimated intake and the sociodemographic characteristics of the population. Multiple regression analysis was employed for the interpretation of hair mercury data in relation to fish consumption frequency, gender and the age of individuals. Mercury concentrations in hair ranged from 0.22 to 9.56 microg g( 1) (geometric mean = 1.79 microg g(-1)) and were closely related to fish intake. Fisherman and their families consumed fish three to five times per week and were the most exposed population subgroup. A high proportion of women of child-bearing age (50%) had relatively high levels of mercury in their hair (3.08-7.88 microg g(-1)). PMID- 17852401 TI - Modelling non-systemic pesticide residues in fruits with initial deposit variability and weather effects. AB - A flexible and generic model was developed to predict the decline of residues of a non-systemic pesticide for both single and multi-spray situations as well as for different tree canopy zones. The model predicts not only the average residue levels, but also the confidence interval of the residues through either a deterministic or a stochastic approach. This generic model includes several key aspects of residue fates in the environment: initial deposit, physical loss and growth dilution. The model considers a tree canopy in three distinct zones for which initial deposition of pesticides may differ. In addition to predicting the average residue within each zone, it also estimates the 95 and 99% confidence intervals of residues on individual fruit within each zone. For the purpose of evaluation, this model was parameterized specifically for captan, one of the most important non-systemic fungicides used to control disease in horticultural crops. The observed average initial deposit for each zone was used in the evaluation. The overall correlation between predicted average residues and those observed on apple fruit in two applications was 0.93. Confidence intervals were also predicted accurately. PMID- 17852402 TI - Exposure to patulin from consumption of apple-based products. AB - Patulin is a mycotoxin produced by species of Penicillium, Aspergillus and Byssochylamys. Several Scientific Committees classify patulin as mutagenic, embryotoxic and immunotoxic. It has been found as a natural contaminant of processed apple products and its presence may be indicative of the quality of fruit used in production. In this work, a method for the analysis of patulin is described, based on a simple liquid-liquid extraction with acetonitrile; patulin is analyzed using liquid chromatography with UV detection. Patulin identity was confirmed by GC-MS after its reaction with N-methyl-N (trimethylsilyl)trifluoroacetamide. Fifty-three apple-containing products were analyzed and patulin was detected in 14 samples in a range 1.5-50.9 microg l(-1); six of which were above the maximum permitted level of the European Union. Based on these results and juice consumption by the Spanish adult population, patulin estimated intake was 0.42 ng kg(-1) body weight per day. PMID- 17852403 TI - Assessment of the stability of pesticides during the cryogenic processing of fruits and vegetables. AB - An evaluation of the stability of pesticides in fruit and vegetables during cryogenic sample processing (comminution of samples in the presence of dry ice) is reported. Pesticides were spiked onto the undamaged surface of individual units of fruit before freezing and comminution. The mean recoveries of pesticides spiked before and after comminution of the sample were compared to determine the relative stability of the individual pesticides during cryogenic sample processing. A stable internal deposition standard (IDS) was used to correct for physical losses and volumetric errors. Mean recovery results together with associated standard errors were obtained using restricted maximum likelihood (REML) analysis. A total of 134 pesticides in four commodities (apples, grapes, lettuce and oranges) were evaluated. The results demonstrated that 120 pesticides were stable (i.e. the mean difference in recovery of pesticides spiked pre- and post-processing was <20%) during cryogenic sample processing. Fourteen pesticides showed some instability or loss (i.e. the mean difference in recovery of pesticides spiked pre- and post-processing was >20%) during cryogenic sample processing: biphenyl, cadusafos, captan, chlorothalonil, dichlorvos, disulfoton, ethoxyquin, etridiazole, heptenophos, malaoxon, phorate, tebuconazole, tecnazene and trifluralin. PMID- 17852404 TI - Running exercise- and antidepressant-induced increases in growth and survival associated signaling molecules are IGF-dependent. AB - It is known that physical exercise increases hippocampal brain-derived neurotrophic factor (BDNF) mRNA and protein, as well as the expression of several pro-survival signaling proteins and that many of these effects depend on the uptake of peripheral insulin-like growth factor-1 (IGF-1) into the CNS. Because treatment with antidepressants has similar effects upon neurotrophin expression, we investigated whether antidepressant-induced BDNF changes also depend on IGF-1 uptake, as well as whether IGF-1 plays a role in the exercise/antidepressant induced expression of molecules associated with plasticity/growth (GAP-43, SCG 10) and the intracellular activation of molecules associated with neuronal survival (Akt, ERK1/2). We evaluated the effects of a well known monoamine oxidase inhibitor, tranylcypromine, on BDNF mRNA and protein levels and phospho Akt and phospho-ERK1/2 immunoreactivity, both with and without systemic blockade of IGF-1 uptake through the use of an antiserum raised against IGF-1. Anti-IGF-1 reversed the increase in BDNF mRNA and protein elicited by exercise as well as tranylcypromine. Exercise also significantly enhanced transcription of axon growth protein, GAP-43, an effect that was also evidenced to be IGF-1-dependent. The combination of exercise-plus-tranylcypromine also increased several cell survival signaling measures, but the BDNF changes associated with the combination treatment appeared to be independent of IGF-1 uptake. Together, these results indicate that the uptake of peripheral IGF-1 in the CNS is essential for antidepressant- as well as exercise-induced enhancement in hippocampal BDNF expression and thus, enhanced hippocampal neuronal survival and plasticity. PMID- 17852405 TI - VEGF-related protein isolated from Vipera palestinae venom, promotes angiogenesis. AB - Therapeutic angiogenesis is one of the major approaches in designing new therapies for cardiovascular diseases. vpVEGF was purified from Vipera palestinae venom using two steps of reverse-phase HPLC. Structurally, vpVEGF belongs to the VEGF-F1 family of snake venom proteins, and potently stimulated dHMVEC proliferation in a VEGFR-2 dependent manner. This growth factor appeared to be a chemoattractant for migration of these cells and stimulated their radial migration in a collagen gel. The stimulatory effect on dHMVEC was correlated with activation of the MAPK Erk1/2 signaling pathway. In vivo vpVEGF induced angiogenesis in a Japanese quail assay and in a Matrigel plug assay in mice. Although in the quail assay vpVEGF showed lower activity than hrVEGF-A165 in mammalian-related systems there were no significant differences. The experiments with dHMVEC, as well as angiogenesis in vivo suggest that the pro-angiogenic effect of vpVEGF is related to its interaction with VEGFR-2 (flk-1). PMID- 17852406 TI - A synthetic, bioactive PDGF mimetic with binding to both alpha-PDGF and beta-PDGF receptors. AB - A multi-domain peptide, PAB2-1c, was designed and synthesized as a bioactive mimic of PDGF. PBA2-1c bound to both alpha- and beta-PDGF receptors as determined by surface plasmon resonance (SPR). The equilibrium dissociation constant (Kd) of binding to alpha-PDGF receptors by PAB2-1c (1.7 x 10(-8) M) compared favorably rhPDGF-AA (1.34 x 10(-8) M). Binding to -PDGF receptor by PAB2-1c (2.2 x 10(-8) M) was less favorable than, that of recombinant human PDGFBB (1.59 x 10(-9) M). Interestingly, PBA2-1c bound to these two receptors with similar affinity suggesting that, PBA2-1c was not PDGF receptor selective. In a murine myoblast cell line C2C12, PBA2-1c increased the tyrosine phosphorylation on PDGF receptors and the phosphorylation of AKT and ERK1/2 in a concentration-related manner. PBA2 1c also stimulated an increase in cell proliferation, cell migration, and collagen gel contraction. In these cell-based assays, PAB2-1c was effective at 1 microg/ml or lesser. The results support the hypothesis that PBA2-1c is a mimetic of PDGF, although it has a more promiscuous receptor interaction. PMID- 17852407 TI - Differential effect of FGF and PDGF on cell proliferation and migration in osteoblastic cells. AB - It has been known that growth factors such as fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) can promote proliferation and migration in a variety of cell types including osteoblastic cells. However, the mechanism underlying their action has not been clearly defined. The present study was undertaken to examine the effect of FGF and PDGF on cell proliferation and migration and to determine the role of extracellular signal-regulated kinase (ERK) and Akt in action of FGF and PDGF in osteoblastic cells. FGF enhanced proliferation in a dose- and time-dependent manner, whereas it did not affect cell migration. FGF induced a transient activation of ERK, but not Akt, which was inhibited by an inhibitor of MEK, the upstream kinase of ERK, but not by inhibitors of PI3K/Akt (LY294002), epidermal growth factor receptor (EGFR, AG1478), and Src (PP2). FGF-induced proliferation was inhibited by inhibitors of MEK/ERK and Src pathways. Exposure of cells to FGF stimulated transition of cell cycle from the G1 phase to S phase and increased phosphorylation of Rb. FGF induced phosphorylation of Rb was attenuated by inhibitors of MEK/ERK and Src pathways. Cell migration studies indicated that PDGF stimulated migration, but it had no effect on cell proliferation. PDGF induced activation of ERK and Akt. The ERK activatin was inhibited by the Src inhibitor and the Akt activation was inhibited by inhibitors of EGFR and Src. PDGF-induced migration was inhibited by inhibitors of MEK/ERK, PI3K/Akt, EGFR and Src pathways. Taken together, these findings suggest that the MEK/ERK and Src pathways play an important role in the FGF-induced proliferation and signaling pathways involving MEK/ERK, EGFR, Src and PI3K/Akt mediate the PDGF-induced migration. These data are of importance in understanding the roles of these growth factors in osteoblastic cell proliferation and migration. PMID- 17852408 TI - Lack of BCL-2 confers interferon-alpha sensitivity to B-cell lymphomas. AB - Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder with pathological manifestations usually including splenomegaly and pancytopenia. Interferons (IFNs), specifically of the alpha subtypes, have shown a significant anti-tumor effect in HCL patients, with improvement of hematological parameters within the first few months of treatment. However, the therapeutic effect of IFN alpha is still rather limited. The mechanisms responsible for the beneficial action of IFN-alpha in HCL patients are unclear. A continuous line of cells (Eskol) from a patient diagnosed with HCL was established and shown to have several properties of HCL. Even though, Eskol cells are very resistant to anti proliferative activity of IFN-alpha, Daudi cells, another human B-cell-derived cell line, are very sensitive to anti-proliferative activity of IFN-alpha and are commonly used as a model cell to test anti-proliferative effect of IFN-alpha. To understand the molecular reason(s) behind the observed obvious differences to IFN sensitivity of above cells, we have analyzed the expression levels of BCL2, caspase-1, Laminin and PARP in these cells. We found that Daudi cells do not express BCL2 at all, and probably because of that, these cells have constantly cleaved, and probably activated form of caspase-1. However, when we over expressed BCL2 in these cells, they lost processed form of caspase-1 and became resistant to anti-proliferative activity of IFN-alpha. These results let us to suggest that IFN-alpha sensitivity of B-cell lymphomas, once again, depends on the presence or absence of BCL2. PMID- 17852409 TI - FGF-4 increases in vitro expansion rate of human adult bone marrow-derived mesenchymal stem cells. AB - Human bone marrow-derived mesenchymal stem cells (MSCs) exhibit limited in vitro growth. Fibroblast growth factors (FGFs) elicit a variety of biological responses, such as cell proliferation, differentiation and migration. FGF-4 represents one of the FGFs with the highest cell mitogenic activity. We studied the effect of FGF-4 on MSCs growth and pluripotency. MSCs duplication time (Td) was significantly reduced with FGF-4 compared to controls (2.2 +/- 0.2 vs. 4.1 +/ 0.2 days, respectively; p = 0.03) while BMP-2 and SCF-1 did not exert a significant growth effect. MSC expression of surface markers, differentiation into adipogenic and osteogenic lineages, and baseline expression of cardiomyogenic genes were unaffected by FGF-4. In summary, exogenous FGF-4 increases the rate at which MSC proliferate and has no significant effect on MSC pluripotency. PMID- 17852410 TI - Different regulation of p27 and Akt during cardiomyocyte proliferation and hypertrophy. AB - Postnatal cardiomyocytes normally grow by hypertrophy but show a limited proliferate response to certain stimuli. Although the proliferative capacity declines shortly after birth, neonatal cardiomyocytes can grow both by hypertrophy and by proliferation. Therefore, we have used neonatal cardiomyocytes to investigate the molecular differences between hypertrophic and proliferative growth of cardiomyocytes. Stimulation of neonatal cardiomyocytes with angiotensin II mainly induced hypertrophy, whereas PDGF only had a minor effect on the size of the myocytes. In contrast, PDGF induced significant proliferation in the cardiomyocyte cultures whereas angiotensin II treatment only resulted in a small increase in the number of cells. Measurement of cyclin D-dependent kinase specific phosphorylation of pRb by immunohistochemistry showed that, both stimuli activate the G1 phase of the cell cycle. By western blotting we found that PDGF induced proliferation correlates with activation of Akt, inactivation of GSK 3beta and downregulation of the cyclin-dependent kinase inhibitor p27, whereas angiotensin II only had a small effect on Akt, GSK-3beta and p27. Our data support the hypothesis that, the hypertrophic and proliferative responses are both activated by G1 cell cycle molecules. The difference between the two responses appears to be that high amounts of p27 are present during hypertrophic growth, whereas proliferation involves downregulation of p27 and GSK-3beta activity and upregulation of Akt. PMID- 17852411 TI - Controlled ovarian hyperstimulation using multi-dose gonadotropin-releasing hormone (GnRH) antagonist results in less systemic inflammation than the GnRH agonist long protocol. AB - OBJECTIVE: The aim of the study was to investigate whether controlled ovarian hyperstimulation (COH) using multi-dose gonadotropin-releasing hormone (GnRH) antagonist results in a lesser degree of systemic inflammation than the GnRH agonist long protocol. DESIGN: Prospective, observational study. PATIENTS AND METHODS: Blood was drawn three times during the COH cycle from patients undergoing the long GnRH-agonist protocol (agonist group) (n = 12) or the multi dose GnRH-antagonist protocol (antagonist group) (n = 15): the day on which adequate suppression was obtained (agonist group), or day 2 or 3 of the menstrual cycle and before gonadotropin treatment (antagonist group) (Day-0); the day of or prior to administration of human chorionic gonadotropin (Day-hCG); and the day of ovum pick-up (Day-OPU). Levels of sex steroids and serum C-reactive protein (CRP) were compared between the two study groups among the three time points. RESULTS: While no between-group differences were observed in patient age or ovarian stimulation characteristics, a significantly higher number of oocytes were retrieved in the antagonist compared with the agonist group. In both groups, serum CRP levels were significantly higher on Day-OPU than on Day-hCG and Day-0. While serum CRP levels were higher on Day-hCG than Day-0, the difference was statistically significant only for the agonist group (p < 0.05). Moreover, Day OPU serum CRP levels were significantly higher in the agonist than in the antagonist subgroup. CONCLUSION: COH using the multi-dose GnRH-antagonist protocol yields a lesser degree of systemic inflammation, as reflected by CRP levels, than the GnRH-agonist long protocol. PMID- 17852412 TI - The effect of estrogens on superoxide anion generation by human neutrophil granulocytes: possible consequences of the antioxidant defense. AB - The present study aimed to test whether, beyond the known antioxidant effect of estradiol, such a property is also possessed by estrone and estriol. For this purpose, an in vitro investigation of the effect of estrone and estriol on superoxide anion production by human neutrophil granulocytes was carried out. Blood samples were obtained from healthy volunteers and neutrophil granulocytes were separated for measurement of superoxide anion generation after incubation with estrone, estriol (10(-7), 10(-6) and 10(-5) M) and 17beta-estradiol (10(-7) M). Superoxide anion production of isolated neutrophil granulocytes was quantified by photometry and using the reduction of ferricytochrome-C. When adding estrone and estriol to neutrophil granulocyte suspensions, the production of superoxide anion fell (10(-5) M: 84.17 +/- 3.14% and 88.77 +/- 1.98% of control production, p < 0.01 and p < 0.05, respectively). Estradiol produced an antioxidant effect at lower concentration (10(-7) M: 72.91 +/- 7.94% of control production, p < 0.001). The weak estrogens estrone and estriol, similarly to estradiol, are also able to reduce the superoxide anion release in our experimental model. This may have importance in the antioxidant defense of biological systems. PMID- 17852413 TI - Ovarian reserve in women with polycystic ovary syndrome who underwent laparoscopic ovarian drilling. AB - OBJECTIVE: To evaluate ovarian reserve assessed by hormones and sonography in women with polycystic ovary syndrome (PCOS) undergoing laparoscopic ovarian drilling (LOD). METHODS: This was a cross-sectional study. Twenty-one PCOS women undergoing LOD were enrolled in the study (the LOD group). Their day-3 anti Mullerian hormone (AMH), inhibin B, follicle-stimulating hormone (FSH) levels, antral follicles count (AFC) and summed ovarian volume representing ovarian reserve were compared with those of PCOS women who did not undergo LOD (the PCOS group) and those of normal ovulatory women (the control group). RESULTS: There were no differences in age and body mass index between groups. AMH levels seemed to be lower in the LOD (4.60 +/- 3.16 ng/ml) than in the PCOS (5.99 +/- 3.36 ng/ml) groups, but did not reach statistical significance. Day-3 FSH levels were significantly higher and AFC was significantly lower in the LOD than in the PCOS group. AMH levels, AFC and summed ovarian volume were significantly greater, but FSH was significantly lower, in the PCOS group compared with the control group. There were no differences in inhibin B levels between groups. CONCLUSION: This study showed that ovarian reserve assessed by hormonal levels and sonography seems to be lower in the LOD than in the PCOS group. The PCOS women both with and without LOD had significantly greater ovarian reserve than the age-matched controls having normal ovulatory menstruation. PMID- 17852414 TI - Pioglitazone for treating polycystic ovary syndrome in non-obese women of reproductive age with different clinical presentations. AB - AIMS: To evaluate the effects of pioglitazone on menstruation and the metabolic parameters of non-obese women of reproductive age with polycystic ovary syndrome (PCOS) and compare the effects among different subgroups of PCOS patients with different clinical presentations. METHODS: Twenty-eight women of reproductive age with PCOS were recruited; 20 women finished the study. The women were divided into three groups according to clinical presentations: group A (n = 4) had chronic oligo- or anovulation with polycystic ovaries; group B (n = 5) had chronic oligo- or anovulation with hyperandrogenism; and group C (n = 11) had chronic oligo- or anovulation, hyperandrogenism and polycystic ovaries. Pioglitazone (15 mg/day) was given for 6 months and the therapeutic effects were evaluated. Menstrual cycle regularity and hormone levels (plasma luteinizing hormone (LH), follicle-stimulating hormone, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, glucose, insulin, C-peptide, free testosterone, homeostatic model assessment (HOMA)) were evaluated during and after pioglitazone treatment. RESULTS: Thirty percent and 45.5% of the patients showed improvement of menstrual cycle regularity immediately after completion of treatment and at 6 months after completion of pioglitazone treatment, respectively, although there were no statistical differences among the subgroups. There was a significant difference in the change of body mass index (BMI) throughout the study period among the subgroups (p = 0.008). The decrease in BMI was significantly higher in group B than in groups A and C at 3 months (p = 0.0381) and 6 months of treatment (p = 0.0054), as well as at 6 months after completion of treatment (p = 0.003). HDL-C concentrations increased throughout the period (p = 0.001) without a difference among the subgroups. LH levels decreased at 6 months of treatment and throughout the follow-up period (p = 0.0045), but this did not differ among subgroups. The free testosterone level decreased, but without significance. There was no statistical improvement in any of the parameters of insulin resistance, but baseline free testosterone levels were related to the improvement of the HOMA insulin sensitivity score (p = 0.0009). Patients with more than a 50% decrease of their HOMA insulin resistance (HOMA-IR) score showed higher baseline free testosterone levels (hyperandrogenic groups B and C) than did the patients with less than 50% HOMA-IR score improvement or those patients with an increased HOMA IR score. CONCLUSIONS: These preliminary results suggest that pioglitazone treatment for non-obese PCOS women of reproductive age may be effective to help the resumption of the menstrual cycle, and the patients showed a different response pattern according to their baseline free testosterone levels. PMID- 17852415 TI - Human endometrium mRNA profile assessed by oligonucleotide three-dimensional microarray. AB - Our purpose, in the present work, was to further comprehend the genetic events underlying the response to steroids of human endometrium from the mRNA as well as protein expression point of view. In order to achieve this goal we undertook 10,000-oligonucleotide, three-dimensional microarray analysis, followed by immunohistochemistry, on human normal endometrium in the proliferative and secretory phases of the menstrual cycle. The results revealed that a myriad of genes involved in immune response, calcium metabolism and thyroid hormone response were frequently overexpressed in the second or luteal phase of the menstrual cycle. During the follicular phase, in contrast, overexpression of genes was mainly restricted to those encoding proteins involved in cell proliferation. PMID- 17852416 TI - Downregulation of beta-catenin and transdifferentiation of human osteoblasts to adipocytes under estrogen deficiency. AB - BACKGROUND AND AIM: Postmenopausal osteoporosis, caused by estrogen deficiency, is characterized by the structural deterioration of bone accompanied by an increase in bone marrow adipocytes. Transgenic animal models have shown that there is a reciprocal relationship between osteoblastogenesis and adipogenesis in vivo. The present study investigated whether the estrogen and the canonical Wnt signaling pathways are linked together and regulate the phenotype and function, differentiation and proliferation of human osteoblasts using an in vitro estrogen deficiency model. METHODS: Human osteoblasts (hFOB 1.19) and fulvestrant, an estrogen receptor blocker, were used to mimic estrogen deficiency in vitro. Osteogenic and adipogenic differentiation was measured by using specific stains and microscopy, as well as by measuring the expression of bone cell-specific markers with reverse transcription polymerase chain reaction. Expression of estrogen receptor-alpha (ERalpha) and beta-catenin was detected in Western blots and by immunoprecipitation. RESULTS: The cells expressed the 46-kDa and the 77 kDa ERalpha isoforms and beta-catenin. Fulvestrant reduced expression of ERalpha and beta-catenin. beta-Catenin was co-immunoprecipitated with ERalpha, indicating that these two proteins form a new signaling complex and transcription factor. In addition, it induced intracellular lipid droplet accumulation and downregulation of bone cell markers, indicating adipocyte differentiation. PMID- 17852417 TI - Allopregnanolone serum concentrations and neurosteroid sensitivity during withdrawal from postmenopausal hormone therapy. AB - BACKGROUND: We have previously compared the pharmacodynamic response to a neuroactive steroid, pregnanolone, before and during sequential treatment with estradiol-only (E2-only) and estradiol together with progesterone (E2 + P) in postmenopausal women. The aim of the present study was to evaluate the pharmacodynamic response to pregnanolone during withdrawal from E2-only treatment and during withdrawal from treatment with E2 + P. METHOD: Twenty-six postmenopausal women were administered hormone therapy (HT) in a randomized, double blinded, placebo-controlled, crossover study. The women received 2 mg oral estradiol continuously during two 28-day cycles and 800 mg vaginal progesterone or placebo sequentially for the last 14 days of each treatment cycle. The pharmacodynamic response to pregnanolone was assessed during the last week of the last treatment cycle and 48 h after termination of the last treatment cycle (withdrawal) by comparing the effects of intravenous pregnanolone (3alpha-hydroxy 5beta-pregnan-20-one) on saccadic eye movements. RESULTS: During E2-only withdrawal the pregnanolone sensitivity was reduced compared with E2-only treatment. Pregnanolone sensitivity remained unaltered between the combined E2 + P treatment regimen and the withdrawal from these steroids. CONCLUSION: The study indicates that withdrawal from E2-only treatment might change neurosteroid sensitivity, whereas the immediate withdrawal from E2 + P results in unchanged neurosteroid sensitivity. PMID- 17852418 TI - Contraception: the need for a new contraceptive revolution. PMID- 17852419 TI - Post-exercise oxidative stress and obesity in postmenopausal women: the role of beta3-adrenergic receptor polymorphism. AB - AIM: Some studies indicate that the Trp64Arg polymorphism in the gene encoding the beta3-adrenergic receptor (ADRB3) is associated with obesity, insulin resistance and earlier onset of type 2 diabetes mellitus. The aim of the present study was to evaluate the frequency of this polymorphism and its relationship with obesity and oxidative stress in postmenopausal women. MATERIAL AND METHODS: We performed the study on 200 women, aged 50-60 years. Estimation of anthropometric parameters and total body fat, android and gynoid fat deposits was carried out using dual-energy X-ray absorptiometry. Oxidative stress was estimated by measurement of thiobarbituric acid-reactive substances (TBARS) in serum. Blood for analysis was collected before, directly after and 6 h after a 30 min physical test on a cycle ergometer. ADRB3 genotyping was performed by polymerase chain reaction. RESULTS: The frequency of Trp64/Arg64 genotype in the investigated population was 12%, and of Trp64/Trp64 was 87%. The Arg64/Arg64 genotype was present in only 1% of women. Women bearing the Trp64/Arg64 genotype did not differ in any measured anthropometric parameters from women bearing the Trp64/Trp64 genotype. Moreover, genotype had no influence on oxidative stress parameters. Likewise, in both groups, mean plasma level of TBARS was increased significantly (p < 0.05) directly after the endurance test and remained elevated 6 h after the test. CONCLUSIONS: The Trp64Arg polymorphism of ADRB3 seems to not be related to obesity in postmenopausal women. Moreover, the Trp64Arg polymorphism has no influence on oxidative stress intensification after standardized physical effort in postmenopausal women. PMID- 17852420 TI - Primary amenorrhea in a young Polish woman with complete androgen insensitivity syndrome and Sertoli-Leydig cell tumor: identification of a new androgen receptor gene mutation and evidence of aromatase hyperactivity and apoptosis dysregulation within the tumor. AB - Primary amenorrhea in 46,XY females can be due to complete androgen insensitivity syndrome (CAIS), pure gonadal dysgenesis, 17-hydroxysteroid dehydrogenase deficiency, or mixed gonadal dysgenesis. The present paper describes a new de novo non-sense mutation in exon 1 (K141Z) of the androgen receptor gene (AR) and the expression in CAIS testis of aromatase, estrogen receptors, as well as proliferation- and apoptosis-associated proteins. CAIS is a rare disease characterized by absent virilization in 46,XY individuals and the development of a female phenotype despite normal or even elevated androgen levels. CAIS is usually caused by a mutation in AR, which leads to organ resistance to androgens. Testicular tumors such as Sertoli-Leydig cell tumor often develop in patients with CAIS. The immunohistochemical findings in the testes of our CAIS patient suggest that the high expression of aromatase and other molecular changes in the testis may be responsible for pubertal breast development and the increased risk of testicular tumor. PMID- 17852421 TI - Chronic inflammation and elevated homocysteine levels are associated with increased body mass index in women with polycystic ovary syndrome. AB - BACKGROUND: Women with polycystic ovary syndrome (PCOS) are insulin-resistant and have increased risk for type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). But it is controversial whether the increased risk of CHD and T2DM is associated with endocrine abnormalities occurring as a consequence of PCOS or whether it is related to obesity or metabolic changes frequently seen in women with PCOS. OBJECTIVE: Since both homocysteine (Hcy) and C-reactive protein (CRP) are supposed to predict T2DM and CHD, we investigated their possible relationship with insulin resistance, obesity, hyperandrogenemia and metabolic alterations in 44 PCOS women and 26 healthy controls matched by age and body mass index (BMI). RESULTS: Hcy and CRP levels were significantly elevated in PCOS women compared with controls (13.30 +/- 4.81 vs. 9.02 +/- 3.36 micromol/l, p < 0.05 and 4.22 +/- 2.95 vs. 2.66 +/- 2.49 mg/l, p < 0.05). There was no correlation between Hcy and CRP (r = 0.171, p = 0.05) as two risk markers. While plasma Hcy levels were correlated with BMI, ratio of luteinizing hormone (LH) to follicle-stimulating hormone (FSH), total testosterone, free testosterone, triglyceride and insulin levels and homeostatic model assessment-insulin resistance index (HOMA-IR) (p < 0.05), CRP was correlated with BMI, total cholesterol, triglyceride, low-density lipoprotein cholesterol and insulin levels and HOMA-IR (p < 0.05). There was no correlation of CRP with parameters of PCOS such as testosterone and LH/FSH ratio (p > 0.05). Multiple regression analysis revealed BMI as the major factor examined that influenced both Hcy and CRP levels. CONCLUSIONS: In PCOS women, plasma levels of Hcy and CRP were significantly elevated compared with age- and BMI-matched controls. Although most of the PCOS-related endocrine and metabolic changes are related to elevated plasma Hcy and CRP levels in PCOS women, BMI seems to be the major factor determining CHD and T2DM in women with PCOS. PMID- 17852422 TI - Thyroid metastasis of endometrial carcinosarcoma associated with Graves' disease. AB - A 54-year-old woman who had undergone total abdominal hysterectomy and bilateral adnexial resection because of endometrial carcinosarcoma presented with thyrotoxicosis, rapidly enlarging neck mass, right cervical tenderness to the ears, palpitation, swelling and heat intolerance, 3 years after the operation. Her serum thyroid hormone levels confirmed hyperthyroidism. Triiodothyronine/thyroxine ratio was 18. The thyroid antibodies were markedly elevated. A thyroid scan showed a cold area corresponding to the thyroid nodule, with high radioiodine uptake in the remaining thyroid tissue. Antithyroid drugs were started to control the hyperthyroidism. In our patient, who had a history of malignancy, the rapidly enlarging neck mass was considered as metastasis to the thyroid gland. The patient underwent bilateral total thyroidectomy. Histopathological examination demonstrated findings compatible with Graves' disease on the left and a carcinosarcoma metastasis on the right thyroid lobe. We suggest that both destructive thyroiditis and Graves' disease contributed to our patient's thyrotoxicosis. Metastatic thyroid carcinoma and destructive thyroiditis should be considered in patients with rapidly enlarging neck mass and a prior history of visceral malignancy. PMID- 17852423 TI - Understanding hormone action: does route of administration matter? PMID- 17852424 TI - Maternal hyperandrogenism beginning from early pregnancy and progressing until delivery does not produce virilization of a female newborn. AB - A 33-year-old primagravida with a history of polycystic ovary syndrome was referred because of symptoms of moderate hyperandrogenism. Serum hormone levels, measured regularly from the 7th week of pregnancy until delivery, showed very high increases of testosterone, androstenedione and estradiol. Ultrasound showed no evidence of adrenal or ovarian masses. She delivered a female newborn with normal female external genitalia. Umbilical cord hormone levels were normal, except for a modest increase of serum testosterone. After delivery the androgen levels of the mother returned to normal and the symptoms of hyperandrogenism were also slightly improved. PMID- 17852425 TI - Impaired growth hormone secretion after glucose loading in non-obese women with polycystic ovary syndrome, possibly related to androgen but not insulin and free fatty acids. AB - BACKGROUND: Secretion of growth hormone (GH) is known to be suppressed in women with polycystic ovary syndrome (PCOS). The suppression may be implicated in the pathogenesis of PCOS. OBJECTIVE: To investigate the cause of suppressive GH secretion in PCOS. METHODS: In order to eliminate the influence of obesity on the variables, all subjects were non-obese. Standard oral glucose tolerance tests (OGTT) were performed in 13 normal women and 15 patients with PCOS. RESULTS: The serum GH level decreased progressively during the OGTT, and the mean area under the curve (AUC) for the GH response was significantly smaller in the PCOS group than in the normal group. A reduction in the level of serum free fatty acids (FFAs) was observed during OGTT, but only the fasting level of FFAs was significantly higher in the PCOS group than in the normal group. The mean AUCs for glucose, insulin and FFA responses in the PCOS group were significantly greater than those in the normal group. There was a significant negative correlation only between AUC(GH) and testosterone (r = -0.4557, p = 0.012). CONCLUSION: Our findings suggest that the cause of susceptibility for GH secretion to be suppressed after glucose loading in non-obese PCOS patients may be hyperandrogenemia. PMID- 17852426 TI - Association study between epidermal growth factor receptor and epidermal growth factor polymorphisms and endometriosis in a Japanese population. AB - OBJECTIVE: We investigated a possible association between endometriosis and polymorphisms in the genes encoding epidermal growth factor (EGF) receptor (EGFR) and EGF in a Japanese population. METHODS: We compared the distribution of the Egfr+2073 A/T and Egf+61 G/A polymorphisms by polymerase chain reaction restriction fragment length polymorphism analysis in 146 affected women and 181 controls. RESULTS: No significant differences in the frequency and genotype distribution of the Egfr+2073 A/T and Egf+61 G/A polymorphisms were found between endometriosis patients with all disease stages and controls. Stratification by disease stage had no effect on the results. CONCLUSION: The Egfr+2073 A/T and Egf+61 G/A polymorphisms are not associated with an increased risk of endometriosis in a Japanese population. PMID- 17852427 TI - Krukenberg tumor mimicking pregnancy luteoma. AB - BACKGROUND: Pregnancy-associated Krukenberg tumor is very rare, and the diagnosis in pregnancy is even more difficult. Usually symptoms are attributed to pregnancy luteomas, which are hormone-active benign neoplasms. CASE: A 22-year-old female presented at the 28th week of gestation with rapid onset of hirsutism and acne since the 20th week of gestation. Physical and ultrasonographic examinations revealed bilateral ovarian solid masses which were considered as pregnancy luteomas. The patient underwent exploratory laparotomy due to the onset of ascites and elevated tumor markers four months after delivery. Histopathologic examination revealed adenocarcinoma with signet-ring-type cells. CONCLUSION: Krukenberg tumors should be considered in the differential diagnosis of pregnancy luteomas. Otherwise, early diagnosis of the tumor can be delayed. PMID- 17852428 TI - Anti-Mullerian hormone levels and antral follicle count in women enrolled in in vitro fertilization cycles: relationship to lifestyle factors, chronological age and reproductive history. AB - The aims of this prospective study were to investigate the relationship between anti-Mullerian hormone (AMH) and antral follicle count (AFC), and to determine whether these markers of ovarian reserve correlate with lifestyle factors, ethnicity, chronological age and reproductive history. Participants were 136 normo-ovulatory women undergoing infertility work-up within 3 months of their first ovarian stimulation cycle for in vitro fertilization. On day 3 of a spontaneous menstrual cycle, a blood sample for measurement of plasma AMH levels was taken and a transvaginal ultrasound scan to determine the AFC (follicles measuring 2-5 mm in diameter) was performed. Information about smoking, body mass index, alcohol consumption, ethnic origin, chronological age, age at menarche, years since menarche and gravidity were recorded using a case report form. The main outcome measures were plasma AMH concentrations and total number of small antral follicles (AFC). Median plasma levels of AMH were 2.0 ng/ml (interquartile range 1.1-3.6) and AFC was 10 (interquartile range 7-15). A positive correlation between AMH and AFC (r = 0.54, p < 0.0001) was found. AMH and AFC correlated negatively with age (r = -0.30, p < 0.001 and r = -0.27, p = 0.001 respectively) and number of years since menarche (r = -0.23, p = 0.007 and r = -0.21, p = 0.015 respectively), but not with any of the other measures. Circulating AMH levels and AFC correlated with each other and declined significantly with age. There were only weak, non-significant, correlations with lifestyle factors and reproductive history. These putative markers could be used individually or together to assess the age-related decline of ovarian function in normo-ovulatory candidates for IVF. PMID- 17852429 TI - Characteristics of different phenotypes of polycystic ovary syndrome in a Bulgarian population. AB - AIM: Our aim was to investigate the percentage occurrence of different phenotypes of polycystic ovary syndrome (PCOS) in a Bulgarian population, and their clinical, biochemical and hormonal characteristics. METHODS: The study included 70 women with PCOS, diagnosed according to the European Society of Human Reproduction & Embryology/American Society for Reproductive Medicine criteria. The women were divided into four phenotypes: hyperandrogenism (HA) + oligo /anovulation (OA) + polycystic ovaries at ultrasound (PCO) (full-blown syndrome, phenotype A); HA + OA (former National Institutes of Health definition, phenotype B); OA + PCO (phenotype C); and HA + PCO (phenotype D). Serum levels of testosterone, immune-reactive insulin, sex hormone-binding globulin, dehydroepiandrosterone sulfate and lipid metabolism parameters were measured. Free androgen index and homeostasis model assessment of insulin resistance were calculated. Body mass index and waist-to-hip ratio were assessed. RESULTS: The percentages of phenotypes A, B, C and D in a Bulgarian population are 58.6%, 11.4%, 10.0% and 20.0%, respectively. The women with the classical form of PCOS (phenotypes A and B) were more obese, had more strongly expressed hyperandrogenemia, and were more insulin-resistant compared with the women of phenotypes C and D. CONCLUSION: There is a significant difference in anthropometric, hormonal and metabolic indices between the classical form and the clinical variants of PCOS in the studied Bulgarian population. PMID- 17852430 TI - Subhepatic retroperitoneal endometrioma: report of a case. AB - A 38-year-old woman with a history of pelvic endometriosis was referred to our surgical department for the treatment of a cystic lesion most probably originating from the liver. At the laparotomy a solitary cyst was found in the retroperitoneum, connected to the inferior surface of the liver, and was resected. Histopathological examination of the resected specimen revealed that it was an endometriotic cyst. The occurrence of endometriotic cyst in the upper abdomen is very rare: there are no published reports of an endometriotic cyst in that anatomic location. The literature on this subject is reviewed. PMID- 17852431 TI - Alterations of hemostasis after laparoscopic and open surgery. AB - BACKGROUND: After tissue injury caused by trauma or surgery, alterations of hemostasis are observed and there is a risk for postoperative thromboembolic complications. Laparoscopic surgery, by causing limited tissue injury, appears to be associated with a lower risk for thromboembolism than open surgery. We conducted a prospective randomized study in order to detect potentially existing differences in activation of coagulation and fibrinolytic pathways between open and laparoscopic surgery. METHODS: Forty patients suffering from chronic cholelithiasis were randomly assigned to undergo open (group A n = 20) or laparoscopic cholecystectomy (group B n = 20) by the same surgical and anesthesiology team. Demographic data were comparable. Blood samples were taken (a) preoperatively, (b) at the end of the procedure, (c) 24 h postoperatively and (d) 72 h postoperatively. The following parameters were measured and compared within each group and between groups: platelets (PLT), soluble fibrin monomer complexes (SFMC), fibrin degradation products (FDP), D-dimers (D-D), fibrinogen (FIB), activated partial thromboplastin time (APTT), prothrombin time (PT). Thrombin-antithrombin III complexes (TAT) were measured at 24 and 72 h postoperatively. Prothrombin fragment 1 + 2 (F1 + 2) was measured at 24 and 72 h postoperatively in 11 patients of group A and 13 patients of group B, respectively. RESULTS: Demographics were comparable between groups. Immediately postoperatively, TAT and F1 + 2 were significantly higher in group A as compared to group B (p < 0.05). They also increased significantly postoperatively as compared to preoperative levels within each group (p < 0.05). D-dimers were significantly higher in group A as compared to group B (p < 0.01) immediately postoperatively. D-dimers also increased significantly postoperatively in group B as compared to preoperative levels (p < 0.001). FIB decreased slightly in both groups at 24 h postoperatively but there was a significant increase in group A as compared to group B (p < 0.01). SFMC were detected twice in group A and only once group B. FDP levels over 5 mug/ml were detected more often in group A than in group B (p < 0.05). No patient from either group suffered thromboembolism or abnormal bleeding as a postoperative complication. CONCLUSIONS: Open surgery as compared to laparoscopic procedures leads to activation of the clotting system of a higher degree. Although of a lower degree, hypercoagulability is still observed in patients undergoing laparoscopic surgery and, therefore, routine thromboembolic prophylaxis should be considered. PMID- 17852432 TI - Protein phosphatase 2A (PP2A) has a potential role in CAPE-induced apoptosis of CCRF-CEM cells via effecting human telomerase reverse transcriptase activity. AB - Caffeic acid phenethyl ester (CAPE) is one of the most effective components of propolis which is collected by honey bees. The aim of this study was to investigate the cytotoxic and apoptotic effects of CAPE in the CCRF-CEM cell line and to clarify the role of serine/threonine protein phosphatase 2A (PP2A) and human telomerase reverse transcriptase (hTERT) activity as an underlining mechanism of CAPE-induced apoptosis. Trypan blue dye exclusion test and XTT methods were used to evaluate the cytotoxicity and ELISA based oligonucleotide detection, which can be seen during apoptosis, was used to determine apoptosis. Acridine orange/ethidium bromide dye technique was also used to evaluate apoptosis. The cytotoxic effect of CAPE was detected in a dose and time dependent manner with the IC(50) of 1 muM. ELISA and acridine orange/ethidium bromide methods have shown remarkable apoptosis at 48th hour in CAPE treated cells. To investigate the role of PP2A in CAPE-induced apoptosis of CCRF-CEM cells, we performed combination studies with CAPE and, Calyculin A and Okadaic acid, which are very well known inhibitors of PP2A, in IC(20) of inhibitors and IC(50) of CAPE. Combination studies revealed synergistic effect of both drugs by concomitant use. Western blot analyses of PP2A catalytic and regulatory subunits showed down-regulation of expression of PP2A catalytic subunit in CAPE treated cells at 48th hour. Since, PP2A is important in hTERT (telomerase catalytic subunit) activation and deactivation, we also performed hTERT activity in CAPE treated cells simultaneously. Treating cells with IC(50) of CAPE for 96 h with the intervals of 24 h showed marked reduction of hTERT activity. The reduction of hTERT activity in CAPE treated CCRF-CEM cells was more prominent in the initial 48 h. The variation of hTERT activity in CAPE treated CCRF-CEM cells may be the reason for the protein phosphatase interaction that occurred after treatment with CAPE. PMID- 17852433 TI - Mechanisms of cellular resistance to imatinib in human chronic myeloid leukemia cells. AB - A major advancement in the treatment of chronic myeloid leukemia (CML) has been the development of imatinib, which has shown striking activity in the chronic phase and the accelerated phase, but less so in the blast phase of the disease. Despite high rates of hematologic and cytogenetic responses to therapy, the emergence of resistance to imatinib has been recognized as a major problem in the treatment of patients with CML. Various cellular mechanisms may be involved in the nature of cellular resistance. Increased amount of target, alteration in structure of target proteins, decreased drug uptake and increased detoxification are well-known mechanisms of resistance. On the other hand, in some cases, even if anticancer drugs reach their sites of action, bypassing drug efflux system of the cells, some cells still may survive via the dysregulation of apoptotic signalling. In this study, mechanisms of resistance to imatinib-induced apoptosis in human Meg-01 CML cells were examined. Continuous exposure of cells to step wise increasing concentrations of imatinib resulted in the selection of 200- and 1000 nM imatinib-resistant sub-lines referred to as Meg-01/IMA-0,2 and Meg-01/IMA 1, respectively. MTT cell proliferation, cell cycle analyses and trypan blue dye exclusion analyses showed that Meg-01/IMA-1 cells were resistant to imatinib induced apoptosis as compared to parental sensitive cells. There was an increased expression of BCR/ABL, Bcl-2 and an increase in mitochondrial membrane potential (MMP) detected in resistant cells comparing to parental sensitive cells. There was no mutation detected in imatinib binding site of ABL kinase region. Various diverse mechanisms have been reported for their involvement in the multidrug resistance. In this study, it has been shown that the degree of BCR/ABL expression appears to be directly proportional to the levels of imatinib resistance. In addition, there have been BCR/ABL-independent mechanisms reported for deriving resistance against imatinib. Our results revealed that besides BCR/ABL overexpression, imatinib resistance also depends on the inhibition of apoptosis as a result of up-regulation of anti-apoptotic stimuli and down regulation of pro-apoptotic stimuli through MMP but does not depend on any mutation on imatinib binding site of ABL kinase. PMID- 17852434 TI - Serum levels, and bone marrow immunohistochemical expression of, vascular endothelial growth factor in patients with chronic myeloproliferative diseases. AB - Current data suggest that angiogenesis plays a significant role in the pathogenesis and progression of chronic myeloproliferative diseases (cMPDs). In the present study, we evaluated serum levels of vascular endothelial growth factor (VEGF) in 83 patients with cMPDs [myelofibrosis with myeloid metaplasia (MMM, n = 25), essential thrombocythaemia (ET, n = 40), polycythaemia vera (PV, n = 8) and chronic myeloid leukemia (CML, n = 10)] and in 27 healthy individuals. Serum VEGF levels were significantly increased in patients with cMPDs compared to healthy individuals (all p values were < or = 0.05) and were significantly correlated with bone marrow microvessel density (MVD) (p = 0.0013). In addition, the immunohistochemical expression of VEGF protein in bone marrow biopsy specimens were analyzed in 61 patients with cMPDs, (ET, n = 36 and MMM, n = 25) and in 27 healthy individuals. The cellular distribution of VEGF expression was similar in bone marrow specimens of patients and healthy individuals. VEGF protein was detected mainly in erythroid cells, whereas myeloid cells and megakaryocytes exhibited a variable expression of the protein. The percentage of bone marrow VEGF positive cells was positively correlated with serum levels of VEGF (p = 0.001). The results of the present study suggest that, VEGF is a major angiogenetic factor in patients with cMPDs and contributes to the pathogenesis of these diseases. PMID- 17852435 TI - Predictive factors of septic shock and mortality in neutropenic patients. AB - Neutropenia is a major risk factor for developing a serious infection. Bacteremia still causes significant mortality among neutropenic patients with cancer. The purpose of this study was to identify risk factors for septic shock and for mortality in neutropenic patients with leukemia and bacteremia. Consecutive samples from 20 patients with acute myeloid leukemia and bacteremia were studied during a 1 year period (January-December 2003). All patients received empirical antibiotic therapies for febrile episodes using ceftazidime plus amikacin. About 110 neutropenic febrile episodes were noted: clinically documented 14.54%, microbiologically documented 16.36% and fever of unknown origin 69.09%. Gram negative organism caused eight febrile episodes: Pseudomonas (5), Klebsiella (3). Gram-positive organism caused 10 episodes: Staphylococcus (6), Streptococci (2), Enterococci (2). Pulmonary infection accounted for 25% of clinically documented infections. About 14 of the 110 febrile episodes were associated with septic shock causing mortality in 7 patients. In a univariate analysis variables associated with septic shock were: pulmonary infection (OR = 17, p = 0.001), serum bicarbonate < 17 mmol/l (OR = 68, p < 0.001) and serum lactate >3 mmol/l (OR = 62, p < 0.001). Variables associated with mortality were: pulmonary infection (OR = 83, p < 0.001) and serum bicarbonate < 17 mmol/l (OR = 61, p < 0.001). In a multivariate analysis two variables were associated with septic shock: pulmonary infection (OR = 5, p = 0.043) and serum lactate >3 mmol/l (OR = 10, p = 0.003). An elevated serum lactate (>3 mmol/l) and low serum bicarbonate ( < 17 mmol/l) at the onset of bacteremia are useful biomarkers in predicting septic shock and mortality in neutropenic patients. PMID- 17852436 TI - Evaluation of bone mineral density in children with hemophilia: Mansoura University children hospital (MUCH) experience, Mansoura, Egypt. AB - BACKGROUND: Patients with hemophilia may be at risk for developing reduced bone mineral density (BMD) for a number of reasons such as recurrent hemoarthrosis and immobilization. AIM OF THE WORK: To assess the BMD in children with hemophilia and to correlate BMD with findings regarding the joint disease (hemophilic arthropathy). PATIENTS AND METHODS: Thirty hemophilic patients aged 4.97 +/- 3.64 years and 30 control healthy individuals (without joint disease) aged 5.09 +/- 3.64 years were selected from the hematology unit and outpatient clinic of MUCH respectively. Anthropometric measurements were carried out in all cases. Z-score was used for weight, height, and body mass index (BMI). Joint evaluation for hemophilic patients and controls was done using Colorado PE-0.5: Half point instrument before using dual energy X-ray absorptiometry (DEXA). DEXA scanning was performed in all hemophilic patients and controls focusing on L2-L4 vertebrae. RESULTS: There was no significant difference between hemophilic patients and controls as regard anthropometric measurements and their Z-score. There was a significant difference between hemophilic patients and controls as regard BMD and BMD Z-score (mean +/- SD) (BMD: 0.48 +/- 0.13 gm/m(2) for hemophilic patients vs. 0.55 +/- 0.14 gm/m(2) for control, p = 0.05, BMD Z-score: - 0.68 +/- 0.44 for hemophilic patients vs. 0.19 +/- 0.14 for controls p = 0.003). There was a significant difference between severe hemophilic patients (factor level assay less than 1%) and controls as regard BMD and BMD Z-score (BMD: 0.41 +/- 0.15 gm/m(2) for hemophilic patients vs. 0.55 +/- 0.14 gm/m(2) for controls, p = 0.01, BND Z-score: - 1.49 +/- 0.12 for hemophilic patients vs. 0.19 +/- 0.14 for controls p = 0.001). Also, in hemophilic patients, there was an inverse significant correlation between total joint evaluation scores and BMD Z score (r = - 0.365, p = 0.04). CONCLUSIONS: Children with hemophilia may have reduced BMD compared with age- and gender-matched controls. This reduction in BMD was independent of differences in age and body size. Children with more established hemophilic arthropathy exhibited the lowest BMD and BMD Z-score. RECOMMENDATIONS: (1) Early detection of osteopenic hemophilic children using DEXA scanning, (2) bisphosphonates plus calcium for hemophilic children with reduced BMD, (3) evaluation of the effect of on demand vs. prophylaxis replacement therapy in hemophilic patients on BMD and hemophilic arthropathy. PMID- 17852437 TI - First report from India of haemolytic disease of newborn by anti-c and anti-E in Rh (D) positive mothers. AB - In India, at the majority of the transfusion centers, antenatal antibody screening is done only in Rh (D) negative mothers. We report here two cases of haemolytic disease of newborn (HDN) by maternal alloimmunization to anti-c in one case, and both anti-c and anti-E in the second case. Both women were Rh (D) positive mothers and HDN was detected postnatally by a positive direct antiglobulin test (DAT) in their newborns. These cases highlight the importance of routine antenatal antibody screening even in Rh (D) positive females. A close follow-up throughout pregnancy is required if irregular antibodies are present so that antigen negative, crossmatch compatible blood can be provided in a timely manner for intra-uterine or exchange transfusions. PMID- 17852438 TI - IgA anti-red blood cell auto-antibodies in Evans syndrome. AB - In Evans syndrome, IgG auto-antibodies (Abs) and/or complement components are frequently detected on red blood cells (RBC) in the direct antiglobulin test (DAT). A 70-year-old man with Evans syndrome diagnosed four years previously presented with a persistent autoimmune haemolytic anaemia, despite immunosuppressive treatment and normalization of platelet count. The RBC allo- and auto-Abs screening and identification were performed by indirect antiglobulin test (IAT) and DAT. In March 2006, no circulating anti-RBC auto-Abs were found in IAT but the DAT was positive with anti-IgG (++), -C3d (weak) and -IgA (++). Follow up for 11 months revealed anti-RBC IgA auto-Abs on five out of six samples. IAT was positive for RBC auto-Abs on three samples. No correlation between the haemoglobin level and the strength of reactivity of IgG and IgA auto Abs was observed. IgA anti-RBC auto-Abs are present in Evans syndrome. To detect these Abs and characterize their role, DAT procedures should systematically include anti-IgA. PMID- 17852439 TI - Failure of puberty in Egyptian beta thalassemic patients: experience in north east region - Dakahlia province. AB - BACKGROUND: Endocrine complications in thalassemia major (TM) are classically considered to be the result of iron deposition in the endocrine glands. Hypogonadotropic hypogonadism, which still remains the commonest endocrinopathy in patients with TM, has been proven to be the result of hemosiderosis of the gonadotroph cells of the pituitary gland. THE AIM OF THE STUDY: To evaluate the prevalence of delayed puberty and hypogonadotropic hypogonadism in transfusion dependent patients with beta-TM. PATIENT AND METHODS: Growth and sexual development of 40 patients with TM (20 males, 20 females) aged 12-22 years were evaluated. Thirty healthy individuals aged 12-20 years served as a control group. The following parameters were measured in every patient: age, sex, height, weight, body mass index (BMI) and Tanner's pubertal staging. For all patients, the following investigations were done: ophthalmological evaluation, audiograms, skeletal survey, echocardiography, serum ferritin, liver function tests, hepatitis profile, serum calcium, phosphorus and blood sugar. Thyroid, parathyroid hormones, serum follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and estradiol (E2) hormone were also measured. RESULTS: Failure of puberty was present in 80% of boys and 75% of girls aged 12 22 years. Gonadotropin insufficiency was found in most of the patients with lack of puberty. Arrested puberty was noted in five boys (25%) and six girls (30%). Ten girls (50%) did not menstruate, two (10%) had oligomenorrhea, one (5%) had irregular menstrual cycles and two (10%) developed secondary amenorrhea. Using univariate analyses and stepwise logistic regression analysis after adjustment for confounding factors, serum ferritin at the time of the study was identified as an independent risk factor for hypogonadotropic hypogonadism, with an odds ratio of 28.40 (95% confidence interval 3.25-245.15), P = 0.003 with a B value of 3.24 (standard error, 1.12). CONCLUSIONS: We conclude that failure of puberty is common in our thalassemic patients which necessitates newer protocols of treatment, correct blood transfusion and chelation therapy. PMID- 17852440 TI - Once weekly recombinant human erythropoietin treatment for cancer-induced anemia in children with acute lymphoblastic leukemia receiving maintenance chemotherapy: a randomized case-controlled study. AB - BACKGROUND: Patients receiving chemotherapy for cancer often develop anemia, which can contribute to increased morbidity and reduced quality of life (QOL). Chemotherapy-induced anemia can be successfully treated using recombinant human erythropoietin (rHuEPO). AIM OF THE STUDY: To demonstrate the effectiveness of once-weekly (QW) rHuEPO dosing to effect improved hemoglobin levels, decreased transfusion use, and improved functional outcomes and QOL in pediatric leukemic patients (ALL) receiving maintenance chemotherapy. PATIENT AND METHODS: This was a prospective randomized, single-center, open-label, 12-week case-control study of epoetin alfa in pediatric patients with acute lymphoblastic leukemia (ALL) in remission receiving maintenance chemotherapy. Sixty patients were randomly assigned to receive either epoetin alfa (rHuEPO group = 30 cases, 17 males and 13 females, age; 6.8 +/- 2.33 years), or no epoetin alfa (control group = 30 cases, 16 males and 14 females, age; 6.76 +/- 2.28 years). Both groups were matched as regard age, sex, baseline Hb concentration, remission state, chemotherapy regimen, numbers and amount of blood transfusion, and leukemia state (both were low and standard risk). Epoetin alfa was administered at a dose of 450 IU/kg, once weekly, subcutaneously (s.c.) for 12 consecutive weeks. Endpoints were changes in hematologic and QOL parameters. RESULTS: Among the 30 patients evaluable for hematologic response, the mean increase in Hb from baseline to time of final evaluation was 3.08 +/- 1.48 g/dl (p < 0.001). An increase in Hb of > or = 2 g/dl, in the absence of blood transfusion, occurred in 70% of patients (21 of 30 patients) who were on the study for > or = 30 days. The overall response rate (Hb increase > or = 2 g/dl or Hb > or = 12 g/dl in the absence of blood transfusion) was 90% (27 of 30 patients). In 30 patients who were evaluable for QOL assessment, epoetin-alpha therapy was found to significantly (p < 0.001) improve mean cancer linear analog scale (CLAS) scores for energy level, ability to perform daily activity, and overall QOL from baseline to the time of final evaluation. QW epoetin-alpha was found to be well tolerated. CONCLUSION: Treatment with QW epoetin-alpha was found to increase Hb levels, decrease transfusion requirement, and improve functional status and QOL in anemic patients with ALL in maintenance receiving chemotherapy. The once-weekly schedule is convenient, safe, and may reduce the burden on patients, parents, and their caregivers by reducing the number of visits to the clinic. PMID- 17852441 TI - Isolated central nervous system relapse during cytologic and molecular hematologic remission in two patients with acute promyelocytic leukemia. AB - Extramedullary involvement in the absence of bone marrow disease is rare in patients with acute promyelocytic leukemia (APL). We report two patients with APL who had central nervous system (CNS) relapse without evidence of cytologic and molecular disease of bone marrow after all-trans-retinoic acid (ATRA) treatment. Both of the patients were treated successfully with combination of intrathecal chemotherapy and radiotherapy with or without systemic chemotherapy. Although increasing number of cases with extramedullary involvement of APL after ATRA including therapy have been reported, further studies with a large series of patients are necessary to determine whether ATRA increases the risk of development of extramedullary involvement of disease in patients with APL. PMID- 17852442 TI - Pattern of iron chelation therapy in Egyptian beta thalassemic patients: Mansoura University Children's Hospital experience. AB - BACKGROUND: The simultaneous use of deferoxamine (DFO) and deferiprone (DFP) has an additive effect in iron excretion in transfusion-dependent thalassemic patients. AIM OF THE WORK: To evaluate the efficacy and safety of a prospective alternating therapy with DFO and DFP in patients with beta-thalassemia major (TM) and increased serum ferritin with DFO monotherapy alone. PATIENT AND METHODS: Sixty patients with beta-TM (mean age +/- SD, 13.05 +/- 6.1, range 10-20 years) with iron overload (serum ferritin > 2000 ng/ml) were studied. They received DFO at a daily dose of 40 mg/kg/day for 5-7 nights/week for the past several years. These patients were randomly assigned either to continue treatment with DFO alone (DFO group, n = 30) or prospectively receive additional alternating therapy with DFP at 75 mg/kg/day for 4 days/week and DFO for the other 2 days/week (alternating therapy group, n = 30). The efficacy of both groups was assessed by measurements of serum ferritin, echocardiography, and 24 h urine iron excretion (UIE) levels throughout 1 year follow-up. RESULTS: In the 60 evaluable patients, the mean serum ferritin ( +/- SD) fell dramatically from 4500 ( +/- 1250) ng/ml at the start of the study to 1250 ( +/- 750) ng/ml (alternate therapy group; P < 0.001) at the end of the study. There was also a significant improvement in the myocardial function as assessed by the ejection fraction (P < 0.002) and fractional shortening (P < 0.01) in those patients on alternate therapy for 1 year. Their mean urinary iron excretion elevated from 0.41 +/- 0.27 to 0.76 +/- 0.49 mg/kg/24 h (P < 0.003). There was a significant difference between both groups as regard the studied parameters at the end of the study. Whereas, there was no statistical difference as regard the studied parameters at the start and the end of the study in the DFO group. No significant adverse effects had occurred in both groups that necessitated withdrawal from the study. CONCLUSIONS: beta-Thalassemic major patients with transfusional iron overload can be safely and effectively treated with an alternate therapy of DFO/DFP with a progressive fall in the mean serum ferritin and significant improvement of myocardial performance. PMID- 17852443 TI - Evaluation of growth parameters in patients with thalassemia major. AB - BACKGROUND: Thalassemia major is a severe hemolytic anemia and the most common single gene abnormality. It is very common in Iran, and needs thorough investigation. If not treated properly, growth failure is one of the most important complications of this disease. This study was designed to evaluate the growth parameters in thalassemic children and compare the obtained data with normal children. MATERIALS AND METHODS: This cross-sectional, descriptive, and analytical study was carried out on 121 thalassemic patients who received blood transfusion therapy in Yasuj, with respect to the physical growth parameters such as height, weight, sitting height and arm circumference. Collected data were compared with data obtained from normal children (chosen from the same sex, age and socioeconomic groups). RESULTS: According to statistical analysis, the weight of 53.7% of thalassemic and 17.1% of non-thalassemic patients, with the same age group, was under the 5th percentile (p < 0.0001). Height and mid-arm circumference were 66.9 vs. 17.1% and 72.7 vs. 32.5% respectively, under the 5th percentile. CONCLUSION: Considering the growth retardation of thalassemic patients, we recommend regular follow-ups with precise intervals for blood transfusion and desferal injection. PMID- 17852444 TI - Myelodysplastic syndrome associated with chronic valproic acid therapy: a case report and review of the literature. AB - This report is of a case of myelodysplastic syndrome occurring in a 63 year old female on long-term valproic acid therapy for seizure disorder. Valproic acid therapy is widely prescribed for seizure disorders and is often associated with thrombocytopenia, macrocytic anemia and a reversible dysmyelopoiesis. There are rare reports in the literature of acute myeloid leukemia arising in patients treated with valproic acid. This case represents the first case report of a cytogenetically confirmed myelodysplastic syndrome occurring in a patient on long term valproic acid therapy and further supports that valproic acid, a histone deacetylase inhibitor, may be leukemogenic. PMID- 17852445 TI - Apoptosis and proliferation differences between CD34+ and CD34- leukemic subpopulations in childhood acute leukemia. AB - In view of the clinical and biological significance of leukemic heterogeneity we studied the efficacy of spontaneous apoptosis and cell cycle distribution in CD34+ and CD34 - leukemic subpopulations. Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) leukemic samples with CD34 heterogeneous expression were separated into CD34+ and CD34 - fractions using fluorescence activated cell sorting. Cell cycle distribution, and apoptosis of the sorted subpopulations were estimated. CD34+ leukemic subpopulations had lower ability to apoptosis than that of CD34 - fractions in 6 out of 8 ALL samples and in 4 out of 5 AML samples. CD34+ fractions showed a higher percentage of proliferating cells compared to CD34 - cells in T-lineage ALL. These differences may lead to a more resistant phenotype of one of the subpopulations and reappearance this population in relapse. PMID- 17852446 TI - Recombinant human granulocyte colony-stimulating factor (rhG-CSF) promotes in vitro platelet aggregation. AB - rhG-CSF is increasingly used for stimulation of granulopoiesis and stem cell mobilization in healthy donors for allogeneic stem cell transplantation. However, a possible association between thrombosis and rhG-CSF administration has been reported. For that reason, in this study, we investigated the effect of rhG-CSF on platelet aggregation in whole blood of 10 healthy volunteers. Three concentrations of rhG-CSF solution (1, 10 and 100 ng/ml) were prepared. Each concentration of rhG-CSF solution and a control diluent without rhG-CSF were incubated with whole blood. Incubation with rhG-CSF solutions would result in 0.1, 1.0 and 10 ng/ml rhG-CSF concentrations in the blood. After incubation, aggregation responses were evaluated with ADP (5 and 10 microM) and collagen (2 and 5 microg/ml) in whole blood. When compared to control, preincubation with all dilutions of rhG-CSF augmented aggregation of platelets induced by ADP and collagen in a statistically significant manner (p < 0.05 for all comparisons). There was also a relationship between rhG-CSF concentration (1, 10 and 100 ng/ml) and augmentation of platelet aggregation response (p < 0.0001 for 5-10 microM ADP; p < 0.0001 for 2-5 microg/ml collagen). In conclusion, this study with an in vitro model showed that rhG-CSF administration may lead to platelet hyperaggregability. PMID- 17852447 TI - Pseudo-Gaucher cells in Hb E disease and thalassemia intermedia. AB - Pseudo-Gaucher cells are morphologic curiosities described in a number of conditions. We report their presence in a bone marrow biopsy and a spleen from 2 patients with hemoglobin E disease and thalassemia intermedia, respectively. The pathogenesis of these cells and their multiple known associations are discussed. PMID- 17852448 TI - Sub classification and clinico-hematological correlation of 40 cases of acute erythroleukemia - can proerythroblast/myeloblast and proerythroblast/total erythroid cell ratios help subclassify? AB - The clinico-hematological profile of 40 cases of acute erythroleukemia (AEL) was evaluated. These were subclassified into three types, namely AML M6a, M6b and M6c based on the myeloblast and proerythroblast percentages. The proerythroblast percentage has been shown to be a prognostic indicator by several studies. As AEL is biologically an "erythroid predominant" disease, two ratios (PE/MB, PE/TEC) with proerythroblasts as numerator have been formulated. An attempt has been made to assess the difference in these ratios in subclassified AEL. There were 29 M6a, 2M6b,and 9 M6 c patients, which were subclassified using the criteria proposed by Mazzella et al. The incidence of AEL in our study was 3.7%, predominantly affecting males with a predilection to younger age in contrast to Western studies. Both PE/MB and PE/TEC ratios were higher in M6b and M6c in comparison to M6a. The subclassification of AEL becomes essential especially in the era of lineage-targeted therapies, which can lead to the development and use of erythroid specific treatments in the near future. PMID- 17852449 TI - Outcome of pregnancy in women treated with all-trans retinoic acid; a case report and review of literature. AB - All-trans-retinoic acid (ATRA) has been proved to be an effective treatment for acute promyelocytic leukemia (APL), inducing remission in more than 90% of cases. Treatment of APL in pregnancy is controversial as the use of ATRA has been questioned due to the teratogenic effect of retinoids. We report a case of pregnancy in a woman exposed to ATRA during the first trimester. The baby was born healthy, without any anomalies. Review of all reported cases of the use of ATRA in pregnancy revealed no serious adverse outcomes or congenital anomalies although only very few cases had exposure in the first trimester. PMID- 17852450 TI - Multiple myeloma staging based on the combination of beta-2-microglobulin and albumin: the role of albumin in the model. AB - BACKGROUND AND OBJECTIVE: Since the prognostic significance of the combination of beta-2-microglobulin (beta(2)m) and albumin in multiple myeloma (MM) has been recognized, these two easily obtainable parameters were subsequently employed in the staging systems of Bataille et al. (BSS), the South West Oncology Group (SWOG SS) and most recently the International Myeloma Working Group (ISS). There is no consensus, however, regarding the cut off levels of beta(2)m and the stage, early or advanced, at which albumin should be added to the model. At the same time, Weber et al. demonstrated similar results using beta(2)m alone in identical cut offs with ISS (WSS). The aim of the present study is to apply these four staging systems in 504 MM patients, in order to discern the role of albumin in MM staging and evaluate if, and at which stage, albumin should be added to the model. METHODS: Median overall survival (OS) according to BSS, SWOG SS, ISS and WSS was estimated according to the Kaplan-Meier method. OS differences between the stages were assessed using the log-rank test. Patients with beta(2)m < 3.5 mg/l and albumin < 3.5 g/dl, who were classified in stage II according to ISS and in stage I according to WSS, were analyzed separately in order to detect in which prognostic group they practically belong. RESULTS: BSS and SWOG SS failed to distinguish stage II from stage III patients and stage III from stage IV patients, respectively. ISS and WSS achieved clear stratification of the patients into three distinct prognostic subgroups, but WSS I patients had a lower life expectancy than ISS I patients. This difference was due to false inclusion of patients with beta(2)m < 3.5 mg/l and albumin < 3.5 g/dl in stage I by WSS, while separate analysis of these patients proved that they belong, in fact, in stage II. In an attempt to improve its prognostic impact, WSS was then successfully modified by dividing WSS I patients in two substages, WSS IA: beta(2)m < 2.5 mg/l and WSS IB: 2.5 mg/l < or = beta(2)m < 3.5 mg/l, thus designating a low-risk and a low-intermediate-risk subgroup, respectively. CONCLUSION: Albumin appears to lose its prognostic value at high cut-off levels of beta(2)m, while it enhances the prognostic significance of beta(2)m at low cut-off levels of the latter. Albumin cannot be eliminated from the ISS, since it is absolutely necessary in order to identify true low-risk patients. The only possibility for albumin exclusion from the model, could be to decrease the beta(2)m low-risk cut-off from 3.5 to 2.5 mg/l. PMID- 17852451 TI - Application of PRV-1 mRNA expression level and JAK2V617F mutation for the differentiating between polycytemia vera and secondary erythrocytosis and assessment of treatment by interferon or hydroxyurea. AB - Increased PRV-1 mRNA expression and the presence of Jak2(V617F) mutation in peripheral blood granulocytes are specific markers for chronic myeloproliferative disorders (MPD), which facilitate the differential diagnosis between polycythemia vera (PV) and secondary erythrocytosis (SE) and may be helpful for monitoring treatment efficacy in MPD patients. We evaluated the presence of the Jak2V617F mutation and increased PRV-1 mRNA expression along with previously established markers - erythropoietin (EPO) independent colony formation (EEC) and erythropoietin level for diagnosis of PV and assessment of treatment efficiency. Increased PRV-1 expression was found in 37 out of 46 patients diagnosed with PV (80%), in 4 out of 15 patients diagnosed with essential thrombocythemia (ET) (27%) and in 4 out of 8 patients with chronic idiopathic myelofibrosis (CIMF) (50%), and increased PRV-1 expression plus EEC formation was observed in 19 of 36 examined MPD patients indicating the superiority of PVSG and WHO bone marrow criteria for the diagnosis of ET, PV and CIMF. We could confirm a very high sensitivity, specificity and utility of the Jak2(V617F) mutation for differential diagnosis between PV and SE. Spontaneous EEC, serum EPO levels, PRV-1 expression was evaluated in 22 PV patients who carried the Jak2(V617F) mutation. A concordance of increased PRV-1 expression and presence of Jak2(V617F) mutation in 19/22 (85%); of increased PRV-1/Jak2/EEC in 14/22 (63%); and of Jak2/PRV 1/EEC/low Epo level in 10/22 (45%) patients was found indicating the superiority of the presence of Jak2(V617F) mutation for the diagnosis of PV. IFN-alpha therapy in patients with PV was more effective then hydroxyurea treatment and significantly reduced increased PRV-1 expression together with higher levels of Jak2(V617F) mutation (50-100%) in PV patients treated with hydroxy urea (HU) and lower levels of Jak2(V617F) mutation (35-90%) in PV patients treated with IFN alpha. Normal PRV-1 expression level was observed in 44% of PV patients who achieved clinical remission and only in 3% of patient who did not. These preliminary observations indicate that the Jak2(V617F) mutation in particular and PRV-1 overexpression appear to be suitable markers for monitoring treatment efficiency in prospective randomised clinical studies comparing pegylated interferon and hydroxyurea in well defined PV patients with a clear indication for cytoreductive therapy. PMID- 17852452 TI - Myelofibrosis with myeloid metaplasia in a patient with relapsed Hodgkin's lymphoma who underwent autologous hematopoietic stem cell transplantation. AB - Second malignancies after autologous haematopoietic stem-cell transplantation (AHSCT) are well-known long-term complications. We present a case of a 24-year old male with relapsed Hodgkin lymphoma (HL) with no involvement of his bone marrow who underwent AHSCT. Four years later he developed mild anaemia and a computed tomography showed an enlarged spleen. As his anaemia worsened, a bone marrow was performed. There was no evidence of HL but intense reticular and collagen fibrosis with hypocellularity was detected. Cytogenetic studies could not obtain cells in metaphase in two occasions. PCR for V617F JAK2 mutation was positive. Until now, with 7 years of follow up from his diagnosis of myelofibrosis with myeloid metaplasia (MMM) he did not require specific treatment besides from red cell transfusions when anaemia worsened during a pneumocistis carinii infection. We present this case, because MMM is a infrequent second neoplasm after AHSCT. Revising the literature we could not find any case like this reported previously. PMID- 17852453 TI - Upregulation of multi drug resistance genes in doxorubicin resistant human acute myelogeneous leukemia cells and reversal of the resistance. AB - The major problem in the treatment of acute myeloid leukemia (AML) patients results from multidrug resistance to administered anticancer agents. Drug resistance proteins, MDR1 and MRP1, which work as drug efflux pumps, can mediate the multidrug resistance of human leukemia cells. In this study, the mechanisms of resistance to doxorubicin-induced cell death in human HL60 AML cells were examined. Continuous exposure of cells to step-wise increasing concentrations of doxorubicin resulted in the selection of HL60/DOX cells, which expressed about 10.7-fold resistance as compared to parental sensitive cells. The expression analyses of MRP1 and MDR1 drug efflux proteins in doxorubicin-sensitive and resistant HL60 cells revealed that there was an upregulation of MRP1 gene in HL60/DOX cells as compared to parental sensitive cells. On the other hand, while there was no expression of MDR1 gene in parental cells, the expression of MDR1 gene was upregulated in HL60/DOX cells. HL60/DOX cells also showed cross resistance to cytosine arabinoside (Ara-c). This resistance was reversed by a combination therapy of Ara-c and cyclosporine A. However, the expression levels of CD15 and CD16 surface markers were significantly decreased in HL60/DOX cells. PMID- 17852454 TI - Rapid transformation of atypical myeloproliferative disorder with consistent t(8;13) to B-cell acute lymphoblastic leukemia: a case report. AB - 8p11 myeloproliferative syndrome (EMS; also known as the stem cell leukemia syndrome-SCLL) is a rare atypical myeloproliferative disorder associated with chromosomal abnormalities involving the 8p11 chromosomal band. Translocations associated with this syndrome result in the fusion of the fibroblast growth factor receptor 1 (FGFR 1) gene with various partners, resulting in ligand independent FGFR activity. The most commonly observed translocation of this syndrome is t(8;13), which results in the expression of a chimeric ZNF198-FGFR1 tyrosine kinase. Disease phenotype associated with this translocation has some typical features such as poor prognosis, and transformation to mainly acute leukemia and non-Hodgkin lymphoma; commonly with a T-cell phenotype in which obtaining and maintenance of remission is difficult by conventional chemotherapy. We hereby present a case diagnosed as atypical chronic myeloproliferative disease with consistent t(8;13)(p12;q12) and transformed rapidly to pre-B-cell acute lymphoblastic leukemia which is a rare clinical presentation. PMID- 17852455 TI - Multidrug resistance inhibition by antisense oligonucleotide against MDR1/mRNA in P-glycoprotein expressing leukemic cells. AB - INTRODUCTION: Acute myeloblastic leukemia (AML) is the most common form of acute leukemia in adults. One major problem in this disease is the emergence of leukemic blast cells that are resistant to anticancer drugs. This phenomenon is termed multidrug resistance (MDR). One cause of MDR is the expression of the MDR1 gene and its product, P-glycoprotein (Pgp). AIM: In the present study, we tried to inhibit the MDR phenotype with MDR1/mRNA/Pgp in leukemic cells using different antisense sequences and two non-viral vectors. MATERIALS AND METHODS: The Pgp expressing cell line was established from a parental K562 (Erythroleukemia) cell line with increasing concentrations of doxorubicin, and named KDI/20. In order to reverse the MDR phenotype due to Pgp expression, four different sequences of sense, antisense and one random sequence with phosphorothioate (PTO) modification (PS-ODN) against MDR1/mRNA were synthesized. They were used on the KDI/20 cells in combination with two non-viral vectors: (1) Fugene 6 transfection reagent (cationic lipid) and (2) polyethylenimine (cationic polymer). The effect of PS ODN was assessed at the cellular level by flow cytometry (for Pgp detection), and Rhodamine 123 assay (for functional assessment of Pgp) at the molecular level by RT-PCR (for MDR1/mRNA detection) and MTT assay in order to assess the sensitivity of cell to doxorubicin. RESULTS: The results showed a decrease in the percentage of Pgp protein and MDR1/mRNA expression and an increase in the accumulation of Rh123 and drug sensitivity of cells to doxorubicin by antisense I and III. The reduction of MDR1/mRNA was more significant than its protein reduction. Therefore, our data showed that antisense can reverse the MDR phenotype at the transcription level and the PEI vector is more efficient than cationic lipid. PMID- 17852456 TI - Therapeutic evaluation and prognostic value of interim hybrid PET/CT with (18)F FDG after three to four cycles of chemotherapy in non-Hodgkin's lymphoma. AB - PURPOSE: Modern risk-adapted treatment requires accurate assessment of the patient's prognosis. This study assessed the value of hybrid PET/CT with 2 [18F]fluoro-2-deoxy-d-glucose ((18)F-FDG) after 3-4 cycles of chemotherapy for early evaluation of response to therapy and prediction of progression-free survival (PFS) in non-Hodgkin's lymphoma (NHL). METHODS: Sixty-one consecutive NHL patients (37 male and 24 female) were included. The (18)F-FDG hybrid PET/CT scans were performed prior to chemotherapy (initial scan) and after 3-4 cycles of chemotherapy (interim scan). Interim FDG findings were correlated to the PFS using Kaplan-Meier analysis. Regression analyses were employed to test for independence of established pretreatment prognostic factors. RESULTS: After 3-4 cycles of chemotherapy, positive (18)F-FDG lesions were found in 28 patients, minimal residual uptake (MRU) in 8 and negative scans in 25 patients. In FDG positive group, 22 patients showed progress and three died. Nine (18)F-FDG negative patients and 4 patients from the MRU group relapsed. Survival analyses showed highly significant associations between early interim FDG imaging and PFS (P < 0.0005). The 2-year PFS rate for FDG-negative patients was 72.2 and 23.0% for FDG-positive patients. The regression model showed that the predictive value of FDG imaging owed its significance to the very high hazard ratio between patients with positive FDG imaging and patients with negative FDG imaging (P < 0.001). CONCLUSIONS: Early interim FDG imaging is an excellent and independent predictor of PFS in NHL. An early assessment of chemotherapy response with FDG scans may provide useful information for selection of patients for alternative therapeutic strategies. PMID- 17852457 TI - Pearson syndrome in an infant heterozygous for C282Y allele of HFE gene. AB - BACKGROUND: Pearson syndrome is a rare mitochondrial disorder characterized by sideroblastic anemia, liver disease, renal tubulopathy and exocrine pancreas deficiency. OBSERVATIONS: We describe a female infant suffering from anemia since birth who gradually developed the complete picture of Pearson syndrome by 13 months. Iron overload was disproportionate to blood transfusions. The patient was heterozygous for HFE gene C282Y mutation (type I hemochromatosis). After an initial response to deferoxamine she presented with cutaneous zygomycosis and died after metabolic derangement and Pneumocystis jiroveci pneumonia. CONCLUSION: This is the second case of a Pearson syndrome individual who was also heterozygous for HFE gene mutation C282Y published. It is also the second case report of a Pearson patient suffering from severe iron overload and liver disease that responded to therapy with deferoxamine. PMID- 17852458 TI - Erythrocyte CD38 as a prognostic marker in cancer. AB - BACKGROUND: Surface antigen CD38 which is a multifunctional protein with enzymatic and receptorial properties is involved in many processes of cell proliferation and activation. It is widely expressed within the hematopoetic system, and its expression is stimulated by proinflammatory cytokines. CD38 associated enzymatic activities in erythrocytes from cancer patients were investigated in this context. METHODS: Erythrocyte NAD glycohydrolase and ADP ribosyl cyclase activities in normal individuals and cancer patients were compared and correlation of these activities to CEA values and anemia were determined. Changes in CD38-expression were followed by SDS-PAGE and Western blot analysis of erythrocyte membrane proteins. RESULTS: Erythrocyte NAD glycohydrolase and ADP-ribosyl cyclase activities were significantly increased in cancer, in parallel to enhancement of CD38 expression and in correlation with CEA values and anemia. CONCLUSIONS: An increased expression of CD38 which may be due to action of proinflammatory cytokines produced in tumor-host reactions appears to account for the elevations in erythrocyte CD38-associated enzyme activities in cancer patients. The changes in these enzyme activities may provide a prognostic outlook in view of their apparently close correlation to tumor progressions. PMID- 17852459 TI - Primary hemostasis in patients treated with LDL-apheresis for severe familiar hypercholesterolemia: a prospective pilot trial using PFA-100 analysis to rationalize therapeutic LDL-apheresis procedure. AB - LDL-apheresis is a method of extracorporeal elimination of serum LDL-cholesterol used for treating patients with severe hyperlipidemia resistant to diet and pharmacotherapy. A practically applicable marker that may possibly be used to ascertain the efficacy of this treatment in lowering the activity of atherosclerosis are still to be found and remains an unresolved problem. Activity of primary hemostasis plays an important role in the process of developing atherosclerotic complications. This fact led us to hypothesize that the investigation of primary hemostatic activity might be a useful marker for monitoring LDL-apheresis efficacy. The aim of this work was to verify this hypothesis. METHODS AND PATIENTS: Commercial analyzer Dade Behring PFA-100, Germany (PFA, platelet function analysis) was used for all investigations. This analyzer enables quantitative measurement of platelet-mediated hemostasis in uncoagulated (citrated) blood. The method simulates platelet activation by mechanical stress (shear stress), and also simulates contact of platelets with collagen. A total of nine long-term treated patients with familial hypercholesterolemia were included in the study group (4 females and 5 males). Ages ranged from 17 to 59 years (average 46.4, median 55). Two patients had homozygous hypercholesterolemia. Eighteen sample pairs were examined using collagen/epinephrine (COL/EPI) membrane and 17 pairs were examined using collagen/ADP (COL/ADP) membrane, the total number of samples amounted to 70. RESULTS: Closure time (CT) values were prolonged after separation in all cases but CT prolongation was not statistically significant (p < 0.14). No differences between homozygous and heterozygous patients were found (p < 0.05). CONCLUSION: Investigation of primary hemostasis using PFA-100 analyzer is not a suitable marker and should not be used to determine the optimal intensity of individual LDL-apheresis procedures. PMID- 17852461 TI - Ninety-six suspected transfusion related acute lung injury cases: investigation findings and clinical outcome. AB - Transfusion related acute lung injury (TRALI) is one of the complications of blood transfusion and can result in major morbidity or mortality. The diagnosis depends upon the application of strict clinical criteria defining acute lung injury (ALI) and a temporal relationship to blood transfusion. We present the clinical and immunogenetic findings of 96 suspected TRALI cases investigated between 1996 and 2004. During this time period the national haemovigilance scheme (UK) defined TRALI as a reaction occurring either during or within 24 h of blood transfusion. Using clinical, laboratory and post mortem evidence, 64/96 cases could be defined as TRALI in our series. Sensitive techniques were employed to screen for HLA class I, class II and granulocyte specific antibodies in donor serum. Donor derived antibodies were detected in 58/64 (90%) of cases. Recipient derived DNA or cells were not always available but incompatibility was confirmed by the presence of the cognate antigen on recipient leucocytes or by crossmatching in 47/64 (73%) of cases. Cases referred prior to 2001 were not tested for HLA class II antibodies. By applying strict clinical criteria and using sensitive techniques a white blood cell antibody mediated immunological pathophysiology can be implicated in the majority TRALI cases. PMID- 17852460 TI - Procoagulant factors in patients with cancer. AB - BACKGROUND: Clotting activation and thromboembolic manifestations are common features in patients with cancer. Tumor cells can directly activate the clotting through two procoagulants: tissue factor (TF) and cancer procoagulant (CP). AIMS: The aim was to evaluate the levels of TF and CP in patients with different tumors in order to: (1) establish an association between these markers and the tumor localization, (2) establish a correlation between the levels of procoagulants and the status of the disease, (3) evaluate if the treatment with chemotherapy induced some modifications on the levels of procoagulants, (4) evaluate the possibility of using procoagulants as predictors in the development of thrombosis. METHODS: Sixty-one patients with different types of cancer (lung, breast, digestive and genitourinary) and 20 normal controls were included. The activity of TF and CP was studied in serum samples. Statistical analysis of the data was performed by two-tailed Fisher exact test. RESULTS: The TF was increased in 72.5 and 0% (p < 0.01) of cancer patients and normal controls, respectively. PC was found to be increased in 88% of the cancer patients but in healthy controls it was increased in only 15% (p < 0.01). The patients with genitourinary cancer presented the highest values of both procoagulants coinciding with a major prevalence of thrombotic events. The activity CP was found in 93% of patients with stages I and II but in patients with stages II and IV disease it was found in 85% (not significant). There were no differences in the levels of both procoagulants between the patients treated with chemotherapy and those with other treatments. CONCLUSIONS: TF and CP are elevated in patients with cancer. The highest values of both procoagulants are in the genitourinary cancer group in agreement with the greater presence of thrombosis observed in this group. Clinical follow up is important in order to determine the potential value of these procoagulants and the tendency to develop thrombosis in patients with cancer. PMID- 17852462 TI - Fixed dose prothrombin complex concentrate for the reversal of oral anticoagulation therapy. AB - Warfarin reversal is frequently required in day to day haematology practice. Prothrombin complex concentrates (PCC) have replaced fresh frozen plasma as the agent of choice in warfarin reversal due to its safety profile. Ideal dose of PCC is still not known and many centres have local guidelines on using the product. We have successfully used PCC (Beriplex) at a fixed dose in our hospital, but we still need randomised control trials to identify the ideal dose of PCC which can result in rapid reversal of warfarin with minimum risk of thrombosis. PMID- 17852463 TI - New insights into paroxysmal nocturnal hemoglobinuria. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is an uncommon acquired hemolytic anemia that manifests with abdominal pain, esophageal spasm, fatigue, and thrombosis. The hallmark of PNH at the cellular level is a deficiency in cell surface glycosylphosphatidylinositol anchored proteins; this deficiency on erythrocytes leads to intravascular hemolysis. Free hemoglobin from hemolysis leads to circulating nitric oxide depletion and is responsible for many of the clinical manifestations of PNH, including fatigue, erectile dysfunction, esophageal spasm, and thrombosis. The recently FDA approved complement inhibitor eculizumab has been shown to decrease hemolysis, decrease erythrocyte transfusion requirements, and improve quality of life for PNH patients. PMID- 17852464 TI - Clonal evolution with +11q 13, t(1;7) and t(1;4) at relapse in a patient with Ph positive acute lymphocytic leukemia (ALL) treated with single agent front line imatinib followed by dasatinib. AB - Imatinib, a selective ABL kinase inhibitor has improved therapeutic outcome in patients with Philadelphia positive chronic or acute leukemia. In the present study, we describe a 56-year-old male with Philadelphia chromosome positive acute lymphocytic leukemia (ALL) who was treated with up-front single agent imatinib and achieved complete hematologic, cytogenetic and molecular remission. At relapse 11 months later, new chromosomal translocations involving chromosomes 1, 7 and 4 and cryptic addition to chromosome 11 were identified in Ph+ cells and the patient had rapid deterioration with progressive disease. The significance of additional chromosomal abnormalities in imatinib treated patients and secondary chromosomal abnormalities in Philadelphia positive chronic myeloid leukemia and ALL are discussed briefly in this report. PMID- 17852466 TI - Evaluation of different coloured carrot cultivars on antioxidative capacity based on their carotenoid and phenolic contents. AB - We compared five new carrot cultivars with a conventional cultivar in consideration of their content of carotenoids, phenolics and according antioxidative capacity. We chose the following cultivars: orange, white, yellow, red, solid-coloured purple and purple with an orange core. Examinations were conducted over two cultivation periods (2003 and 2004). The white, yellow and solid-coloured purple cultivars showed quite low contents of carotenoids, but the solid-coloured purple contained most phenolic compounds. The red cultivar was the only that contained lycopene. The content of carotenoids varied slightly between the two years; alpha-carotene showed noteworthy differences in the orange cultivar and the purple cultivar with an orange core. The higher alpha-carotene content resulted in a higher antioxidative capacity. Also, the lycopene content in the red cultivar was higher in 2004 than in 2003, which again lead to an increased antioxidative capacity. In the case of phenolics, higher values were found for the purple-coloured cultivars in 2004, which only in the case of the purple cultivar with an orange core, however, led to a higher antioxidative capacity. PMID- 17852467 TI - Effect of temperature and salt concentration on rheological behavior of whey protein isolate-starch mixed dispersions. AB - Extensive studies have been carried out on the effect of temperature and salt concentration on the theological behavior of whey proteins and different starches individually, but not on mixed dispersions of whey protein isolates and starches. In the present studies, the rheological behavior of cross-linked waxy maize starch and whey protein isolate mixed dispersions during heating at 60-85 degrees C was investigated. Further, the effect of CaCl2 (25-100 mM ionic strengths) on the gelatinization of these dispersions was determined. It was found that at a 2:3 ratio and a 3:2 ratio of cross-linked waxy maize starch to whey protein isolate mixed gels form a compatible networkmM concentration the solution viscosity was higher. PMID- 17852468 TI - Antioxidant properties of Viburnum opulus and Viburnum lantana growing in Turkey. AB - In the present study, antioxidant properties of the water extracts of different parts of Viburnum opulus and Viburnum lantana (Caprifoliaceae) were investigated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and superoxide anion scavenging methods. The extracts were prepared from the fruits, branches, and leaves of V lantana and V opulus species. The branch extracts of V lantana and V opulus inhibited superoxide anion in a concentration-dependent manner. Compared with t-tocopherol, the fruit extract of V lantana did not show any scavenging effect on superoxide anion formation. V lantana leaf extracts, however, showed a moderate scavenging effect on superoxide anion formation, whereas V lantana branch extracts showed a strong scavenging effect (IC50 = 3.1 mg/ml) on superoxide anion in higher concentration. On the other hand, all extracts exhibited a scavenging effect on the DPPH radical with various potencies. When compared with butylated hydroxytoluene, V opulus branch and V lantana leaf extracts, as well as V lantana branch, V opulus fruit and V lantana fruit extracts, showed strong DPPH radical scavenging activity with IC50 values of 0.014, 0.035, 0.052, 0.057 and 0.085 mg/ml, respectively. PMID- 17852469 TI - Ethnoecology of traditional leafy vegetables of the Luo people of Bondo district, western Kenya. AB - Diversity of traditional leafy vegetables consumed by the Luo people of Nyang'oma, Bondo District, western Kenya, was evaluated in relation to their ecological habitats. The study generally revealed high species diversity within different ecological areas. A total of 60 leafy vegetable species (domesticated and wild) belonging to 47 genera and 29 families were collected. Most of the vegetable species were gathered from the wild but a few were domesticated on farmlands and kitchen gardens. Plant families that comprised most leafy vegetable species were Fabaceae, Amaranthaceae, Acanthaceae, Asteraceae and Solanaceae. PMID- 17852470 TI - Changes in the quality of surimi made from thornback ray (Raja clavata, L. 1758) during frozen storage. AB - Surimi was prepared from the thornback ray (Raja clavata L. 1758) and divided into two groups. The first group was prepared with 4% sorbitol, 4% sucrose and 0.3% sodium tripolyphosphate as a cryoprotectant, while surimi in second group was prepared with 8% sorbitol and 0.3% sodium tripolyphosphate. The frozen surimi samples were stored at 23.8 +/- 2 degrees C for 6 months. The total volatile basic nitrogen (8.40 mg/100 g for group A, 6.30 mg/100 g for group B), trimethylamine nitrogen (2.55 mg/100 g for group A, 2.38 mg/100 g for group B), thiobarbituric acid (1.29 mg malondialdehyde/100 g for group A, 1.17 mg malondialdehyde/ 100 g for group B), and pH values (7.34 for group A, 6.98 for group B) of surimi increased during frozen storage but remained within the acceptable limits. Total psychrophilic aerobic bacteria counts and sensory evaluation points in both groups decreased during frozen storage. The results of this study showed that thornback ray was found to be suitable for surimi production and the surimis were still acceptable at the end of the 6-month storage period. PMID- 17852471 TI - Retinol and alpha-tocopherol concentrations in breast milk of Turkish lactating mothers under different socio-economic status. AB - Retinol and alpha-tocopherol levels in breast milk of Turkish mothers under different socioeconomic status were investigated. Mature milk samples were collected from 92 lactating mothers living in Izmir and in Manisa, cities of Turkey, who were at 60-90 days of the lactating period. Socio-economic, anthropometric, and dietary data were collected by means of a questionnaire. The body mass index was used to determine the nutritional status. The retinol and alpha-tocopherol contents of breast milk were determined by high-performance liquid chromatography; the concentration of alpha-tocopherol was 9.84 microg/ml whereas retinol levels were 81.5 microg/100 ml. The questionnaire survey was used to determine the level of these vitamins in the daily ration of the women. No significant differences were found in terms of milk retinol and alpha-tocopherol levels for the variables income, educational level and mothers' body mass index. PMID- 17852472 TI - Physico-chemical characteristics, nutrient composition and consumer acceptability of wheat varieties grown under organic and inorganic farming conditions. AB - PURPOSE: The aim of the investigation was to analyse physico-chemical characteristics, nutrient composition and consumer acceptability of wheat varieties grown under organic and inorganic farming conditions. METHODS: The seeds of five varieties of wheat (C-306, WH-283, WH-711, WH-896 and WH-912) grown under organic and inorganic farming conditions were ground in a Junior Mill to pass through 60-mesh sieves and were stored in air-tight containers until use. Standard methods were used to estimate the physico-chemical characteristics and nutrient composition. Consumer acceptability was studied by carrying out the organoleptic evaluation of wheat chapatis, a common item in diets of the Indian population. FINDINGS: The results of study revealed that inorganically grown wheat varieties had significantly higher 1,000-grain weight and more grain hardness as compared with organically grown wheat varieties, and a non significant difference was observed in their gluten content, water absorption capacity and hydration capacity. On average, wheat varieties grown under inorganic conditions contained significantly higher protein and crude fibre content as compared with varieties grown under organic conditions. WH-711 variety had maximum protein content. Protein fractions (i.e. albumin, globulin, prolamin and glutelin) were significantly higher in varieties grown under inorganic conditions than those of varieties grown under organic conditions. The variety WH 711 had the highest total soluble sugars and variety WH-912 had the highest starch content. Phytic acid and polyphenol contents were significantly higher in inorganically grown wheat varieties as compared with organically grown wheat varieties. The wheat varieties grown under organic conditions had significantly higher protein and starch digestibility than the wheat grown under inorganic conditions. The data revealed that there were significant differences in total calcium and phosphorus contents of wheat varieties grown under organic and inorganic conditions. The extractability of phosphorus and magnesium was significantly higher in wheat varieties grown under inorganic conditions as compared with grown under organic conditions. A significant difference was observed for the total zinc content of wheat varieties grown under organic and inorganic conditions. The total copper and manganese contents were significantly higher in inorganically grown wheat varieties as compared with organically grown wheat varieties. The organoleptic evaluation of chapatti prepared from varieties WH-711 and WH-912 both grown under organic and inorganic conditions showed no significant difference in their sensory attributes for colour, appearance, flavour, texture, taste and overall acceptability. RESEARCH IMPLICATIONS: The nutrient composition of both organic and inorganic wheat varieties is comparable and protein digestibility is higher in wheat varieties grown under organic conditions. The people of North India, where wheat is a staple cereal, can therefore be encouraged to use organically grown wheat varieties as they are free from hazardous effects of synthetic pesticides/fertilizers. PMID- 17852474 TI - Estimation of daily human intake of food flavonoids. AB - The daily intake of food flavonoids was determined using a semiquantitative food frequency questionnaire (FFQ) and a 4-day food record (4DFR) in a group of 45 female Flemish dietitians. The subjects were asked to report their food intake three times: day 1 using the FFQ (FFQ1); between days 2 and 13 using a 4-day non consecutive food diary (4DFR); and again using the FFQ on day 14 (FFQ2). The total flavonoid intakes (mean and standard deviation) as estimated with the different methods were: for FFQ1, 166.0 +/- 146.6 mg/day; for 4DFR, 203.0 +/- 243.2 mg/day; and for FFQ2, 158.3 +/- 151.8 mg/day. There was a significant different estimate for the amount of flavan-3-ols, flavanones and flavones when comparing the two FFQs with the 4DFR. The two research methods classified 88% of the 45 dietitians in the same or in an adjacent quartile for total flavonoid intake. The findings of this study indicate that the developed FFQ seems to be a simple and reliable method to assign subjects in quartiles of flavonoid intake. PMID- 17852477 TI - Effect of a blueberry nutritional supplement on macronutrients, food group intake, and plasma vitamin E and vitamin C in US athletes. AB - Antioxidants from a blueberry beverage may impact plasma vitamins. We examined vitamins/food selection in 12 college athletes during 30 days compared with placebo. Blood was collected before and after exercise at the beginning of the study (day 1) and then after a 30-day period of taking a daily supplemental beverage (day 30). The six trials involved blood that was drawn pre-beverage ingestion/pre-exercise (trials 1 and 4), post-beverage ingestion/pre-exercise (trials 2 and 5), and post-beverage ingestion/1 h post-exercise (trials 3 and 6), on day 1 (trials 1, 2, and 3) and day 30 (trials 4, 5, and 6). Analysis of variance revealed non-significant differences for macronutrient or gamma tocopherol and vitamin C intakes by food frequency questionnaire or plasma vitamins by liquid chromatography. There was a trend (P = 0.083) in the group x time interaction for alpha-tocopherol intake by repeated-measures analysis of variance. Blueberry alpha-tocopherol (23.91 +/- 9.31 mg) was significantly (P < 0.05) higher than placebo alpha-tocopherol intake (7.59 +/- 0.95 mg) on day 1, but not on day 30 (blueberry, alpha-tocopherol = 9.04 +/- 2.35 mg, placebo, alpha tocopherol = 11.46 +/- 3.65 mg) by pairwise comparisons. Blueberry supplementation did not affect plasma vitamin concentrations or gamma-tocopherol and vitamin C intakes, and may reduce alpha-tocopherol intake in those starting with a higher alpha-tocopherol intake, yet not altering athletes' eating habits. PMID- 17852478 TI - Determination of the mineral content of bee honeys produced in Middle Anatolia. AB - The mineral content of 43 honey samples from the middle regions of Turkey was investigated. Minerals were determined by inductively coupled plasma-atomic emission spectrophotometer. Calcium, potassium, sodium and phosphorus were the most abundant of the elements in all the studied honeys, with average concentrations ranging between 40.13 and 189.69 mg/kg for calcium, 161.01 and 598.62 mg/kg for potassium, 9.34 and 45.9 mg/kg for sodium, and 460.11 and 3,776.96 mg/kg for phosphorus. Cluster analysis of the honey data revealed that the mineral content of Corum and Konya honeys was closer as they formed a cluster at a similarity level of 60%. PMID- 17852479 TI - Preferences and perceptions of personal vegetable consumption: a study among young men in the Norwegian National Guard. AB - A survey was developed to assess the intake, main sources and preferences related to vegetables among 578 male recruits (response rate 78%), in addition to perceptions of personal vegetable consumption. The recruits' average vegetable intake (including potatoes) was 244 g/day. Six per cent of the recruits consumed the recommended 450 g/day or more of vegetables. However, 33% of all recruits stated that they consume enough vegetables. The most important sources of vegetables were potatoes and hot composite dishes for lunch and dinner. High (> or = 282 g/day) and low (< or = 182 g/day) consumers had distinctly different patterns of vegetable consumption. The hot dishes were a more important source among low than high vegetable consumers (P < 0.01). Several recruits reported liking raw (76%) and cooked (58%) vegetables, and preferences were positively related to the vegetable intake (P < 0.02) and (P < 0.001). The results suggest some optimistic bias among the recruits regarding their personal vegetable consumption. PMID- 17852480 TI - Influence of micronutrients on rheological characteristics and bread-making quality of flour. AB - Studies were carried out to see the influence of different iron and calcium salts along with some vitamins on the rheological characteristics and bread-making quality of wheat flour. Fortification with iron (30-90 ppm) from different sources showed a marginal increase in water absorption (2%). Calcium ranging between 800 and 1,600 ppm did not show any influence on the mixing properties of the dough. Except for ethylenediamine tetraacetic acid and calcium lactate, all other salts did not have any influence on the alveograph characteristics. The gelatinization temperature slightly increased by about 2-3 degrees C and the cold paste viscosity increased from 468 to 524 BU. Addition of micronutrient premix containing ferrous sulphate, calcium carbonate and vitamins such as thiamine (thiamine hydrochloride), riboflavin, niacin (nicotinic acid) and folic acid at different levels showed a marginal effect on the rheological parameters. There was no significant influence of micronutrient premix on the objective and subjective evaluation of the breads, except for the crumb colour. Fortification with the vitamin-mineral premix did not affect the theological parameters and bread-making quality of flour, even after storage. PMID- 17852481 TI - Food choice and food consumption frequency for Uruguayan consumers. AB - The aims of the present work were to study motives underlying Uruguayan consumers' food choice behaviour and to study the consumption frequency of some selected food items. A modification of the Food Choice Questionnaire and a food frequency questionnaire was administered to a group of 200 Uruguayan consumers. Feeling good and safety, sensory appeal and health and nutrient content were rated as the most important factors, while familiarity was rated as the least important. Using hierarchical cluster analysis, three clusters with different choice patterns were identified. Frequency of consumption of fruits, vegetables, milk and dairy products, and whole cereals, increased as the importance attributed to health and nutrition increased; consumption of fatty foods decreased. PMID- 17852482 TI - Vitamin A liver store: a case-control study. AB - The present study aims to assess the vitamin A liver store in individuals who died of several causes and to compare them with those who died of violent causes. A case-control study was performed with 60 individuals, where 30 died of violent causes (control) and 30 of other causes (cardiovascular diseases, infections, other chronic degenerative diseases, several causes). According to the cause of death, the mean retinol from liver stores was 281.5 +/- 63.50 mg/g for individuals who died of violent causes--a significantly higher amount (P < 0.05) than those observed in the other group (105.4 +/- 87.54 mg/g by cardiovascular diseases, 88.1 +/-78.03 mg/g by infections, 162.4 +/- 119.19 mg/g by other chronic degenerative diseases and 205.5 + 126.63 mg/g by several causes). The highest prevalence of low vitamin A was observed in individuals who died of infections and cardiovascular diseases, which emphasizes the role of vitamin A in these pathological processes. PMID- 17852483 TI - Content and in-vitro accessibility of pro-vitamin A carotenoids from Sri Lankan cooked non-leafy vegetables and their estimated contribution to vitamin A requirement. AB - Vitamin A deficiency is a public health problem in Sri Lanka, which affects especially pre-school children. Carrots (Daucus carota), pumpkins (Cucurbita maxima), squashes (Cucurbita moschata) and sweet potatoes (Ipomoea batatas) of orange, yellow-fleshed varieties are good sources of provitamin A carotenoids, but have not been studied in Sri Lanka in terms of the food as eaten. The content of carotenoids in each preparation method and the in-vitro accessibility of beta carotene and alpha-carotene were determined by high-performance liquid chromatography. The in-vitro method simulates the conditions in the human intestinal tract. The mean contents in dry weight (DW) in different carrot preparations ranged from 406.7 to 456.3, from 183.7 to 213.5 and from 29.0 to 39.6 microg/g for beta-carotene, alpha-carotene and lutein, respectively. The content of carotenoids in different pumpkin preparations varied from 282.1 to 294.4 microg/g DW for beta-carotene, from 155.6 to 157.7 microg/g DW for alpha carotene and from 218.0 to 228.2 microg/g DW for lutein. The squashes preparation had 44.6 and 40.0 microg/g DW for beta-carotene and alpha-carotene, respectively, and in sweet potatoes beta-carotene ranged from 204.3 to 210.3 microg/g DW. The results showed that the contribution to the recommended daily allowance is greater when these vegetables are prepared as a curry with coconut milk. The percentage contribution to recommended daily allowance from each vegetable cooked with coconut milk was 46.7, 21.8, 1.2 and 10.8 for carrots, pumpkins, squashes and sweet potatoes, respectively. PMID- 17852484 TI - Effect of extrusion cooking on anti-nutritional factor tannin in linseed (Linum usitatissimum) meal. AB - PRIMARY OBJECTIVE: Various oilseeds and their by-products usually constitute a major source of dietary protein as aquafeeds for warmwater herbivorous/omnivorous fish species. The oilseed meals available in India are fairly rich in protein and most of them are traditionally used as valuable feed for farm animals. However, among the factors that limit incorporation of these ingredients in aquafeeds are amino-acid imbalance and presence of anti-nutritional factors. Enhancement of the nutritive value of these ingredients and reduction (or removal) of anti nutritional factors can be attempted by processing so as to increase the bio availability of these nutrients. It has been found that various anti-nutritional factors can be destroyed by the process of extrusion cooking. Extrusion is a process whereby raw feed material is exposed to controlled conditions of high temperature, pressure and moisture. In the present experiment, extrusion cooking is used to reduce the anti-nutritional factor tannin in linseed (Linum usitatissimum) meal. RESEARCH DESIGN: A single-screw cooking extruder, designed and manufactured at the Indian Institute of Technology, Kharagpur, was used for the study. Experiments were carried out following a rotatable central composite design to determine the optimum values of the process variables for which maximum reduction of tannin (Y) occurs. The process variables selected for the study were: barrel temperature (X1) (60-100 degrees C), extruder speed (X2) (60-100 rpm) and oilseed moisture content (X3) (30-50%). Following the design, a second order response model was fitted. MAIN OUTCOMES AND RESULTS: The optimized values of the process variables were found to be X1 =82.5 degrees C, X2 = 90 rpm and X3 = 41.22%, and the value of the predicted response (i.e. reduction of tannin Y) was found to be 61.25%. PMID- 17852485 TI - Antioxidant activities of the water-soluble fraction in tempeh-like fermented soybean (GABA-tempeh). AB - Tempeh is a traditional fermented soyfood native to Central Java, Indonesia; tempeh is prepared by salt-free aerobic fermentation using Rhizopus. Similar to miso, tempeh is also reported to be antioxygenic. In this study, we used a tempeh like fermented soybean. First, soybean was incubated aerobically and then successively incubated anaerobically. Because the gamma-amino butyric acid (GABA) content was increased remarkably, we named this tempeh GABA-tempeh. The contents of other free amino acids and peptides were significantly higher in GABA-tempeh than in conventional tempeh. In this study, we compared the antioxidant activity of the water-soluble fraction in GABA-tempeh with that of soybean and conventional tempeh. The order of the antioxidant activity was shown as follows: GABA-tempeh > conventional tempeh > soybean. The components responsible for the antioxidant activity of GABA-tempeh were isoflavone aglycones, free amino acids, and peptides, which increased during aerobic and anaerobic fermentations. PMID- 17852487 TI - Evaluation of the microelement profile of Turkish hazelnut (Corylus avellana L.) varieties for human nutrition and health. AB - In this study, the levels of boron (B), cobalt (Co), copper (Cu), chromium (Cr), iron (Fe), lithium (Li), nickel (Ni), selenium (Se) and zinc (Zn) microelements in 16 hazelnut samples were determined by inductively coupled plasma mass spectrometry and atomic absorption spectroscopy after microwave digestion, and are discussed for human nutrition and health. Significant differences were observed between the microelement contents of the 16 varieties (P < 0.01). The average microelements concentrations in the varieties varied in the following ranges: B, 13.63-23.87; Co, 0.47-0.82; Cr, 0.22-0.52; Cu, 16.23-32.23; Fe, 31.60 51.60; Li, 0.035-0.042; Ni, 0.58-2.58; Se, 0.96-1.39; and Zn, 22.03-44.03 mg/kg. These results showed that hazelnuts can be an important microelement source for human nutrition and health. According to our trace element data, a daily consumption of 50 g hazelnut can supply easily about 6% for B, 9% for Co, 19% for Fe, 9% for Ni and 16% for Zn of the recommended daily allowance. On the other hand, Se, Cu and Cr levels of 50 g hazelnuts are higher than the respective daily requirements, but slight overdoses of these elements are non-toxic for human health. PMID- 17852488 TI - Influence of a deficit irrigation regime during ripening on berry composition in grapevines (Vitis vinifera L.) grown in semi-arid areas. AB - A study was made of the effects of irrigation management strategies during ripening on the quality of Spanish field-grown grapevine (Vitis vinifera L.) cultivars (Baladi, Airen, Montepila, Muscat Blanc a Petits Grains and Pedro Ximenez) grown under the "Montilla-Moriles" Appellation of Origin in Cordoba, Spain. From 1999 to 2002, two water-availability regimes were established: irrigation and non-irrigation. The study aimed to ascertain the effect of irrigation on berry development and ripening, and hence on grape juice quality. Changes in phenological stages, vegetative growth, vineyard yield, berry weight, total soluble solids, titrable acidity, pH, tartaric acid, malic acid, and potassium content were monitored. No significant differences were noted in phenological phases between the non-irrigation and deficit irrigation regimes. The Ravaz index, pruning weight, vineyard yield and berry weight were significantly higher in all varieties and years under deficit irrigation. Deficit irrigation induced higher titrable acidity, higher malic acid and potassium contents and a lower pH, but had no significant effects on berry sugar accumulation or tartaric acid content. Deficit irrigation thus appears to be a promising technique for the production of quality young wines in semi-arid areas. PMID- 17852489 TI - Nutritional quality evaluation of velvet bean seeds (Mucuna pruriens) exposed to gamma irradiation. AB - Effects of gamma irradiation on Mucuna pruriens seeds at various doses (0, 2.5, 5, 7.5, 10, 15 and 30 kGy) on the proximate composition, mineral constituents, amino acids, fatty acids and functional properties were investigated. Gamma irradiation resulted in a significant increase of crude protein at all doses, while the crude lipid, crude fibre and ash showed a dose-dependent decrease. Raw Mucuna seeds were rich in minerals (potassium, phosphorus, calcium, magnesium, iron and selenium). Sodium, copper and manganese were significantly decreased on irradiation at all the doses, while magnesium and iron showed a significant decrease only above 10 kGy. The essential amino acids of raw and gamma-irradiated Mucuna seeds were comparable with the FAO/WHO recommended pattern. A significant increase of in vitro protein digestibility was seen in seeds irradiated at 30 kGy. High amounts of unsaturated fatty acids in Mucuna seeds decreased significantly after irradiation. However, linoleic acid was not present in raw seeds but detected after irradiation and it was elevated to high level at 30 kGy. Behenic acid, a major anti-nutritional factor, was reduced significantly on irradiation, indicating the positive effect of gamma irradiation on Mucuna seeds. Significant enhancement in the water absorption and oil absorption capacities, protein solubility, emulsion activity and improvement in the gelation capacity was recorded after irradiation. Results of the present investigation reveal that application of gamma irradiation does not affect the overall nutritional composition and can be used as an effective method of preservation of Mucuna seed and their products. PMID- 17852490 TI - Some compositional properties and mineral contents of carob (Ceratonia siliqua) fruit, flour and syrup. AB - The approximate composition and mineral contents of carob fruit (Ceratonia siliqua), and the traditional foods produced from this fruit, carob flour and carob syrup, were studied. Protein, crude fiber and ash content and energy values of carob syrup were lower than the values of both carob fruit and carob flour. According to the results, the total sugar content, the most important constituents of carob products, were 48.35%, 41.55% and 63.88% for fruit, flour and syrup, respectively. These products contained high amounts of calcium, potassium, magnesium, sodium and phosphorus, which were the most abundant elements in carob fruits (P < 0.05). Among the samples, potassium, phosphorus and calcium had the highest values in carob syrup, respectively. Carob flour also contained these elements in high amounts, with the addition of sodium. We extended the notion that carob fruit, flour and syrup were rich sources of carbohydrates, proteins and minerals. PMID- 17852491 TI - Some quality aspects of fish patties prepared from an Indian major carp, Labeo rohita (Ham.). AB - Six different types of fish patties were prepared from de-boned meat of three weight groups (250 500 g, 501-750 g, and 751-1,000 g) of an Indian major carp, Labeo rohita, using two extenders (boiled potato and corn flour). The weight of the fish and the type of the extender affected the nutritional quality of the patties. Cooking lowered the crude protein but increased the total lipid, total soluble sugars, and contents of the patties. Cooking yield increased with an increase in the weight of the fish. Similarly, the use of corn flour as the extender resulted in a higher cooking yield and higher fat retention capacity than boiled potato. The type of extender had no effect on the water-holding capacity of the patties. The weight of the fish and the extender had no significant effect on appearance, colour, flavour, taste, and the overall acceptability of the product. However, the patties prepared from 250-500 g and 501-750 g weight groups with corn flour as the extender had a significantly higher score for their texture. The total plate count suggested that the patties were safe (from microbiological point of view) up to a storage period of 80 days. PMID- 17852492 TI - Effects of fully and partial substitution of NaCl by KCl on physico-chemical and sensory properties of white pickled cheese. AB - White pickled cheeses were produced with different salting treatments, vacuum packed in polyethylene containers, and stored at 4 +/- 1 degree C for 90 days. Five different concentrations of NaC1, KC1 or NaCl/KCl mixtures (sample A, 100% NaCl; sample B, 100% KCl; sample C, 75% NaCl + 25% KCl; sample D, 50% NaC1+50% KCl; sample E, 25% NaCl+75% KCl) were applied in the production of cheeses. Some physical, chemical and sensory properties of the samples were monitored at 0, 15, 30, 60 and 90 days of ripening. The results obtained indicated that the cheese could be produced with the mixture of 75% NaCl + 25% KCl without negative effects on cheese quality. PMID- 17852493 TI - Development and characterization of structured lipids containing capric and conjugated linoleic acids as functional dietary lipid molecules. AB - Recently, dietary oil with high diacylglycerol (DAG) contents, so called DAG-oil, was introduced in Japan and the USA. It was claimed that the oil mostly composed of DAG is metabolized differently from conventional triacylglycerol oil, reducing body weight and fat mass because DAG tends to be oxidized to provide energy rather than stored as fat in the body. Monoacylglcyerol and DAG could be prepared by lipase-catalyzed reactions including hydrolysis, esterification, and glycerolysis. In this study, modified lipid containing some DAG esterified with the health-beneficial medium-chain fatty acids and conjugated linoleic acid was produced by lipase-catalyzed reactions. Many health benefits of medium-chain fatty acids (C6:0-C12:0) and conjugated linoleic acid isomers have been reported, including anticarcinogenic and antiatherogenic activities, and being rapid energy sources for humans with little or no deposition as body fat. The produced lipid molecules in this study have potential applications as functional healthy dietary fats and oils. PMID- 17852496 TI - The antioxidant activities of natural sweeteners, mogrosides, from fruits of Siraitia grosvenori. AB - To search for antioxidant agents from natural resources, in this paper the in vitro antioxidant activities of two natural sweeteners, mogroside V and 11-oxo mogroside V isolated from the fruits of Siraitia grosvenori, were determined using chemiluminescence (CL). The results showed that these sweet glycosides, having cucurbitane triterpenoid aglycon, exhibited significant inhibitory effects on reactive oxygen species (O2-, H2O2 and *OH) and DNA oxidative damage. 11-oxo mogroside V showed a higher scavenging effect on O2- (concentration at which 50% of chemiluminescence intensity is inhibited [EC50] =4.79 microg/ml) and H2O2 (EC50 = 16.52 microg/ml) than those of mogroside V. However, mogroside V was more effective in scavenging *OH, with EC50 =48.44 microg/ml compared with that of 11 oxo-mogroside V (EC50 = 146.17 microg/ml). Further, 11 -oxo-mogroside V exhibited a remarkable inhibitory effect on *OH-induced DNA damage with EC50 = 3.09 microg/ml. PMID- 17852498 TI - Determination of mineral contents of bee honeys produced in Middle Anatolia. AB - The mineral contents of 43 honey samples from the middle regions of Turkey were investigated. Minerals were determined by inductively coupled plasma-atomic emission spectrophotometry. Calcium, potassium, sodium and phosphorus were the most abundant of the elements in all samples with average concentrations ranging between 40.13 and 189.69 mg/kg for calcium, 161.01 and 598.62 mg/kg for potassium, 9.34 and 45.9 mg/kg for sodium, and 460.11 and 3,776.96 mg/kg for phosphorus. Cluster analysis of the honeys' data revealed that mineral contents of Corum and Konya honeys were closer as they formed a cluster at a similarity level of 60%. PMID- 17852499 TI - Nutritional quality of organic, conventional, and seasonally grown broccoli using vitamin C as a marker. AB - Organically labeled vegetables are considered by many consumers to be healthier than non-organic or 'conventional' varieties. However, whether the organic labeled vegetables contain more nutrients is not clear. The purpose of this study is to examine the nutritional quality of broccoli using vitamin C, a fragile and abundant nutrient, in broccoli as a biomarker. The vitamin C content was assayed (2,6-dichlorophenolindophenol method) in broccoli samples obtained from supermarkets that are considered the point of consumer consumption. These samples were obtained during different seasons when the broccoli could be either harvested locally or shipped far distances. The findings indicate that vitamin C could be used as a marker under a controlled laboratory environment with some limitations and, although the vitamin C content of organically and conventionally labeled broccoli was not significantly different, significant seasonal changes have been observed. The fall values for vitamin C were almost twice as high as those for spring for both varieties (P=0.021 for organic and P=0.012 for conventional). The seasonal changes in vitamin C content are larger than the differences between organically labeled and conventionally grown broccoli. PMID- 17852500 TI - The potential of milk thistle (Silybum marianum L.), an Israeli native, as a source of edible sprouts rich in antioxidants. AB - The potential of wild plants in Israel as sources of edible sprouts has not been investigated until now. Milk thistle (Silybum marianum L.) is native to the Mediterranean basin and is now widespread throughout the world; its young fleshy stems are traditionally eaten by the local Arab sector in Israel, and its sprouts are rich in antioxidants and have been used as a traditional medicine for diseases of the liver and biliary tract. The active extract of milk thistle, silymarin, is a mixture of flavonolignans and is a strong antioxidant that has been proved to promote liver cell regeneration, to reduce blood cholesterol and to help prevent cancer. The present objective was to investigate the potential of milk thistle as a source of edible sprouts rich in antioxidants. We found that seed germination within 3-4 days was high (96%, except for striated seeds). Exposure to light significantly reduced sprout growth and significantly increased the polyphenol content and antioxidative capacity. The polyphenol content was 30% higher in seeds originating from purple inflorescences than in those from white ones. We thus found milk thistle to be a good candidate source of healthy edible sprouts. PMID- 17852501 TI - In vitro studies of polyphenol compounds, total antioxidant capacity and other dietary indices in a mixture of plants (Prolipid). AB - The best health and nutrition results can be achieved not only from the consumption of fruits and vegetables with high antioxidant capacities, but also from medicinal plants and herbs. Therefore, in the present investigation, the bioactive compounds (polyphenols and flavonoids) and the radical scavenging capacities of Prolipid, a mixture of herbs, were studied. Water extracts showed relatively high capacity of about 61.5% inhibition with the beta-carotene linoleic acid assay. In order to support the data obtained with beta-carotene linoleic acid assay, three different antioxidant assays were used: ferric reducing/antioxidant power, trolox equivalent antioxidant capacity, and 1,1 diphenyl-2-picrylhydrazyl radical with prolonged time of their reactions. It was found that the amounts of polyphenols in water and methanol extracts were 22.849+/-2.267 and 3.241+/-0.325 mg gallic acid equivalent/g dry weight, and the antioxidant capacities in same extracts as determined by the 2,2'-azinobis (3 ethylbenzothiazoline-6-sulfonic acid) test after 120 min were 275.81+/-27.58 and 62.25+/-6.11 micromole Trolox equivalents (microMTE) g dry weight, respectively. The correlation coefficients between polyphenols and antioxidant capacities of Prolipid with 1,1-diphenyl-2-picrylhydrazyl radical and beta-carotene linoleic acid assay were about 0.97 and 0.98. In conclusion, the bioactivity of Prolipid was high and the total polyphenols were the main contributors to the overall antioxidant capacity. The results of our investigation in vitro are comparable with other medicinal plants and fruits widely used in the treatment of humans without known side effects. Prolipid, a mixture of herbs, can therefore be used as a supplement for nutritional and healthy purposes. PMID- 17852502 TI - Partial replacement of NaCl can be achieved with potassium, magnesium and calcium salts in brown bread. AB - OBJECTIVE: To develop a reduced-sodium bread in which salt (NaCl) is partially replaced with potassium, magnesium and calcium salts. METHODS: Experimental bread was compared against standard brown bread, after a drop test (to assess whether bread quality deteriorates with abuse) and after the usual baking practices for baking properties (volume, crust colour, crumb colour and cell structure), sensory properties and nutritional composition. Plant production feasibility was evaluated in an industrial plant. Breads produced there were subjected to sensory evaluation using triangulation tests in a panel of 122 consumers. Twenty-four samples of both standard and experimental bread were laboratory-analysed for sodium, potassium, magnesium and calcium content. RESULTS AND CONCLUSION: A 32.3% reduced-sodium brown bread was developed that was acceptable in terms of baking qualities, appearance, texture and taste. The potassium, magnesium and calcium contents of the bread were increased by 55.2%, 69.0%, and 34.8%, respectively. PMID- 17852503 TI - Study on beta-galactosidase enzymatic activity of herbal yogurt. AB - Different types of herbal yogurts were developed by mixing standardized milk with pretreated herbs, namely tulsi leaf (Ocimum sanctum), pudina leaf (Mentha arvensis) and coriander leaf (Coriandrum sativum), with leaves separately and a 1:1 (v/v) mixture of the strains of lactic starter cultures---Lactobacillus acidophilus (NCIM 2903) and Lactobacillus plantarum (NCIM 2083)-followed by incubation at 40 degrees C for 6 h. The beta-galactosidase enzymatic activity of the abovementioned herbal yogurts was determined and interestingly noted to exhibit higher enzymatic activity compared with the control yogurt (without any herbs). Among all herbal yogurts, tulsi yogurt had the maximum beta-galactosidase activity. PMID- 17852504 TI - Biological properties of different protein extracts from selenium-enriched Ganoderma lucidum. AB - Our previous studies showed that Ganoderma lucidum bio-transformed 20-30% of inorganic selenium from substrate to organic forms by preferentially incorporating selenium into proteins. In the present study, four kinds of protein extracts from selenium-enriched G. lucidum were prepared with different extracting solvents, which contain water-soluble, alkaline-soluble, salt-soluble and alcohol-soluble protein extracts, and the effects on antioxidant activity of characterizations of protein extracts were studied. Results showed that water soluble extract showed strongest antioxidant properties among all extracts as suggested by spin trapping experiment due to its characterizations, followed by the alkaline-soluble > the salt-soluble > the alcohol-soluble protein extracts, a result demonstrating that selenium content and amino acids composition of the protein extracts play important and direct roles in enhancing their antioxidant activities, and the protein distribution and sugar content have an indirect effect by influencing the characters and structures. The activity of water soluble crude protein was verified by CuSO4 Phen-Vc-H2O2-DNA chemiluminescent analysis, and it should be selected as the subject to be studied and purified further. PMID- 17852508 TI - Changes in nutrient components during ageing of emerging juvenile bamboo shoots. AB - The newly emerging, tender juvenile shoots of bamboos that belong to the tribe Bambuseae, subfamily Bambusoideae of family Poaceae, are edible. Their rich content of amino acids, proteins, carbohydrates, vitamins, minerals and low fat content attracts many people to consume bamboo shoots. A study was conducted to determine the nutrient changes in emerging juvenile shoots of five commercially important bamboos. It was observed that whereas nutrient components of the shoots depleted in all the five species with ageing, the dietary fibre and moisture content were increased. Vitamins and mineral content also decreased in the older shoots. The present study indicates that the freshly emerging juvenile shoots are nutritionally superior to the older emerged shoots. PMID- 17852509 TI - Fatty acid composition of frequently consumed foods in Turkey with special emphasis on trans fatty acids. AB - Fatty acid compositions of frequently consumed foods in Turkey were analyzed by capillary gas chromatography with particular emphasis on trans fatty acids. The survey was carried out on 134 samples that were categorized as meat products, chocolates, bakery products and others. The meat products except chicken-based foods have trans fatty acids, arising as a result of ruminant activity, with an average content of 1.45 g/100 g fatty acids. The conjugated linoleic acid content of meat and chicken doner kebabs were found higher than other meat products. Chocolate samples contained trans fatty acids less than 0.17 g/100 g fatty acids, with the exceptional national product of chocolate bars and hazelnut cocoa cream (2.03 and 3.68 g/100 g fatty acids, respectively). Bakery products have the highest trans fatty acid contents and ranged from 0.99 to 17.77 g/100 g fatty acids. The average trans fatty acid contents of infant formula and ice-cream, which are milk-based products, were 0.79 and 1.50 g/100 g fatty acids, respectively. Among the analyzed foods, it was found that coffee whitener and powdered whipped topping had the highest saturated fatty acid contents, with an average content of 98.71 g/100 g fatty acids. PMID- 17852510 TI - Mineral content of traditional leafy vegetables from western Kenya. AB - Socio-economic changes that have taken place in Africa have influenced people's eating habits in both rural and urban set-ups. Most people prefer introduced foods to traditional foods, including plant foods whose consumption is widely regarded as a primitive culture manifesting poor lifestyles. However, recent studies on traditional plant foods have shown that some are highly nutritious; containing high levels of both vitamins and minerals. They also have potential as a remedy to counter food insecurity since most are well adapted to the local environment, enabling them to resist pests, drought and diseases. This paper describes the mineral (calcium, iron and zinc) contents in some 54 traditional vegetable species collected from Nyang'oma area of Bondo district, western Kenya. Atomic absorption spectroscopy was used to determine the mineral content. We found that most traditional leafy vegetables, domesticated and wild, generally contain higher levels of calcium, iron and zinc compared with the introduced varieties such as spinach (Spanacia oleracea), kale (Brassica oleracea var. acephala) and cabbage (Brassica oleracea var. capitata). The results of this study could contribute towards identification, propagation and subsequent domestication and cultivation promotion of nutrient-rich and safe species within the farming systems of the local communities in Kenya, sub-Saharan Africa or elsewhere. PMID- 17852511 TI - Composition of the non-protein nitrogen fraction of goat whole milk powder and goat milk-based infant and follow-on formulae. AB - The non-protein nitrogen fraction of goat whole milk powder and of infant and follow-on formulae made from goat milk was characterized and compared with cow milk powder and formulae. Goat milk infant formula contained 10% non-protein nitrogen, expressed as a proportion of total nitrogen, compared with 7.1% for cow milk formula. Goat follow-on formula contained 9.3% and cow 7.4% non-protein nitrogen. Urea, at 30%, was quantitatively the most abundant component of the non protein nitrogen fraction of goat milk and formulae, followed by free amino acids at 7%. Taurine, glycine and glutamic acid were the most abundant free amino acids in goat milk powders. Goat milk infant formula contained 4 mg/100 ml total nucleotide monophosphates, all derived from the goat milk itself. Goat milk has a very different profile of the non-protein nitrogen fraction to cow milk, with several constituents such as nucleotides at concentrations approaching those in human breast milk. PMID- 17852512 TI - Multifunctional in vitro antioxidant evaluation of strawberry (Fragaria virginiana Dutch.). AB - Berries have shown the highest potential antioxidant activity among fruits using a unique antioxidant method. The antioxidant activity of aqueous-organic extracts of strawberry (Fragaria virginiana Dutch., var. camarosa) were determined using three methods: 2,2-diphenyl-1-picrylhydrazyl (DPPH*) radical scavenging, antioxidant ferric-reducing power (FRAP), and inhibition of Cu(II)-catalysed in vitro human low-density lipoprotein (LDL) oxidation. A serving (100 g) of strawberry had a DPPH* activity equivalent to that of 183 mg vitamin C and to that of 483 mg vitamin E. In addition, strawberry extracts showed high efficiency in the FRAP assay and in the in vitro inhibition of LDL oxidation. Regression linear analysis between radical scavenging activity (EC50 parameter) and total phenol content from strawberry extracts gave a statistically significant correlation (r = 0.984, P < 0.05). In conclusion, strawberry showed significant antioxidant capacity in both aqueous and lipophilic models. PMID- 17852513 TI - Influence of phytin phosphorous and dietary fibre on in vitro iron and calcium bioavailability from rice flakes. AB - The study was undertaken with the objective of analysing the bioavailable iron, calcium and related constituents in rice flakes of four different thicknesses. Rice flakes of four different thicknesses were procured from four different commercial sources. They were analysed for moisture, mineral, iron, calcium, phosphorous, dietary fibre and phytin phosphorous using standard methods. Bioavailable iron and calcium were estimated using the equilibrium dialysis method. The thickness of flakes ranged from 0.08 to 1.20 mm for thin to thick flakes. The mineral content of the flakes ranged from 0.5 to 1.2 g, iron content from 3.38 to 6.86 mg and calcium content from 107 to 210 mg/100 g in samples of different thickness. Phosphorous (111-430 mg/100 g), phytin phosphorous (23-164 mg/100 g) and dietary fibre (5.64-11.5 g/100 g) reduced with the degree of flaking. The percentage of available iron ranged from 7% to 26% and that of available calcium from 8% to 25% from thick to thin flakes, but the differences were nonsignificant. Multiple regression analysis of the data showed a significant association of phytin phosphorous and dietary fibre (dependent variables) for binding of iron and calcium. PMID- 17852515 TI - Risk factors and geographical heterogeneity in unintentional home injuries incidence rate: new evidence based on Multiscopo survey in Italy. AB - Home injuries together, with road traffic accidents, are estimated to be the third cause of death in Italy (Arokiasamy and Krishnan 1994). However, as in most other countries, in Italy there is a lack of information on home injuries and on how differences in geographical patterns may influence the scope and magnitude of this phenomenon. By analysing a multipurpose large survey (Multiscopo) carried out annually, geographical heterogeneity in home injuries incidence rate can be investigated. The aim of this study is the assessment of possible differences in geographical patterns among the Italian regions making use of a re-analysis of Multiscopo home injury data. The study results show that Italian regions differ greatly in the number of home injuries. The geographical heterogeneity may be due to the unemployment rate and the incidence of poverty that is greater in the Southern and Insular regions than in other zones. Other socio-economic variables such as alcohol consumption can increase the risk of injury in the home. To prevent them it could be useful to organize campaigns aimed at increasing the awareness among people about this problem. PMID- 17852514 TI - Conductive interstitial thermal therapy device for surgical margin ablation: in vivo verification of a theoretical model. AB - PURPOSE: To demonstrate the efficacy and predictability of a new conductive interstitial thermal therapy (CITT) device to ablate surgical margins. METHOD: The temperature distributions during thermal ablation of CITT were calculated with finite element modelling in a geometrical representation of perfused tissue. The depth of ablation was derived using the Arrhenius and the Sapareto and Dewey (S&D) models for the temperature range of 90 to 150 degrees C. The female pig animal model was used to test the validity of the mathematical model. Breast tissues were ablated to temperatures in the range of 79-170 degrees C, in vivo. Triphenyltetrazolium chloride viability stain was used to delineate viable tissue from ablated regions and the ablation depths were measured using digital imaging. RESULTS: The calculations suggest that the CITT can be used to ablate perfused tissues to a 10-15 mm width within 20 minutes. The measured and calculated depths of ablation were statistically equivalent (99% confidence intervals) within +/- 1mm at 170 degrees C. At lower temperatures the equivalence between the model and the observations was within +/- 2 mm. CONCLUSION: The CITT device can reliably and uniformly ablate a 10-15 mm wide region of soft tissue. Thus, it can be used to secure negative margins following the resection of a primary tumor, which could impede local recurrences in the treatment of local diseases such as early staged, non-metastatic, breast cancer. PMID- 17852516 TI - Ability of children with language impairment to understand emotion conveyed by prosody in a narrative passage. AB - BACKGROUND: Several recent studies have indicated that children with language impairment experience difficulty with various aspects of emotion understanding. Because emotion understanding skills are critical to successful social interaction, it is possible that these deficits play a role in the social problems frequently experienced by children with language difficulties. AIMS: To explore further the emotion understanding skills of children with language impairment, the investigation examined the ability of these children to understand emotion conveyed by prosody in a narrative passage. METHODS & PROCEDURES: Nineteen children with language impairment and their chronological age-matched peers served as participants. Children were sampled from the age range of 8-10; 10 years. These children were presented with a seven-sentence narrative read by actors to express happiness, anger, sadness, and fear. They were then asked to indicate what emotion the speaker expressed. OUTCOMES & RESULTS: Children with language impairment performed significantly more poorly than their typical peers in identifying the emotion expressed in the passage. There were also differences between emotions, with happiness being the easiest emotion to identify and fear the most difficult. The interaction between group and emotion type was not statistically significant. CONCLUSIONS: The results provide additional evidence that children with language impairment may have impairments in emotion understanding. If these findings are replicated, interventions designed to facilitate emotion understanding as an aspect of social communication should be considered for some children with language impairment. PMID- 17852517 TI - Narrative skills, cognitive profiles and neuropsychiatric disorders in 7-8-year old children with late developing language. AB - BACKGROUND: A community-representative sample of screened and clinically examined children with language delay at 2.5 years of age was followed up at school age when their language development was again examined and the occurrence of neuropsychiatric/neurodevelopmental disorder (attention deficit/hyperactivity disorder (ADHD) and/or autism spectrum disorder (ASD)) was documented. AIMS: (1) To determine whether these 7-8-year-old children with a history of language delay have deficits in narrative skills compared with the age norms of standardized tests; and (2) to analyse if there is a relationship between narrative outcome, cognitive profile, and neuropsychiatric diagnosis. METHODS & PROCEDURES: Twenty one children recruited from a community sample and with a history of language delay underwent an in-depth multidisciplinary examination at 7-8 years of age. Their narrative and cognitive skills were examined using the Bus Story Test, the Narrative Memory Subtest from the Developmental Neuropsychological Assessment (NEPSY), and The Wechsler Intelligence Scale for Children III (WISC-III). OUTCOMES & RESULTS: The three measures of the Bus Story Test (information, sentence length, and subordinate clauses) were below age norms for all 21 children, of whom 13 also had a neuropsychiatric diagnosis, i.e. ADHD and/or ASD. Half of the children with language delay had problems on Bus Story Test Information and on the Narrative Memory subtest independently of co-occurrence of neuropsychiatric disorder. The only difference across the children with language delay pure and those who had language delay plus ADHD or language delay plus ASD was on Freedom from Distractibility, where children with ADHD and ASD scored low. In addition, children with ASD had a much lower overall cognitive level (FSIQ) and poorer results on Processing Speed. CONCLUSIONS: Swedish children with late developing language at 2.5 years of age have persisting difficulties with oral narrative skills at age 7-8 years. However, almost none of the children with language delay had problems when responding to story-related questions- irrespective of whether or not they had an additional diagnosis of ADHD or ASD. Thus, asking story-related questions may be a good intervention strategy when working with these children. Because narrative difficulties are a reflection of linguistic, cognitive and/or pragmatic/social difficulties, it is important for clinicians of different specialties to work in close collaboration in order to establish a reliable measure that can be used in clinical assessment. Poor results on the WISC-III Kaufman Freedom from Distractibility factor had a strong relationship with a neuropsychiatric diagnosis (not just ADHD), whereas poor results on Bus Story Test Information or NEPSY Narrative Memory (measured as Free Recall) did not. Narrative problems were present among the language delay children even in the presence of adequate speech and verbal comprehension. Thus, narrative assessment may be a useful tool for identifying children with more persistent subtle language and pragmatic problems who are at risk for academic failure. PMID- 17852518 TI - Comparing language profiles: children with specific language impairment and developmental coordination disorder. AB - BACKGROUND: Although it is widely recognized that substantial heterogeneity exists in the cognitive profiles of children with Developmental Coordination Disorder (DCD), very little is known about the language skills of this group. AIMS: To compare the language abilities of children with DCD with a group whose language impairment has been well described: children with Specific Language Impairment (SLI). METHODS & PROCEDURES: Eleven children with DCD and 11 with SLI completed standardized and non-standardized assessments of vocabulary, grammatical skill, non-word repetition, sentence recall, story retelling, and articulation rate. Performance on the non-standardized measures was compared with a group of typically developing children of the same age. OUTCOMES & RESULTS: Children with DCD were impaired on tasks involving verbal recall and story retelling. Almost half of those in the DCD group performed similarly to the children with SLI over several expressive language measures, while 18% had deficits in non-word repetition and story retelling only. Poor non-word repetition was observed for both the DCD and the SLI groups. The articulation rate of the children with SLI was slower than that of the DCD group, which was slower than that of typically developing children. CONCLUSIONS: Language impairment is a common co-occurring condition in DCD. The language profile of children with either DCD or SLI was similar in the majority of, but not all, cases. PMID- 17852519 TI - Phonological awareness, reading accuracy and spelling ability of children with inconsistent phonological disorder. AB - BACKGROUND: Although children with speech disorder are at increased risk of literacy impairments, many learn to read and spell without difficulty. They are also a heterogeneous population in terms of the number and type of speech errors and their identified speech processing deficits. One problem lies in determining which preschool children with speech disorder will have difficulties acquiring literacy skills. AIMS: Two studies are presented that investigate the relationship between speech disorders and literacy. The first examined the phonological awareness abilities of children with different types of speech difficulties. The second study investigated the literacy skills of children with a history of inconsistent speech disorder. METHODS & PROCEDURES: Experiment 1 measured the syllable segmentation, rhyme awareness and alliteration awareness of 61 preschool children: 46 with speech disorder (14 with delayed development, 17 who made consistent non-developmental errors, and 15 who made inconsistent errors) and 15 typically developing controls. Experiment 2 assessed the reading accuracy, spelling and phonological awareness abilities of nine 7-year-old children with a history of inconsistent phonological errors. OUTCOMES & RESULTS: The first study indicated unexpected patterns of performance. While the Delayed group performed less well than controls on all tasks, the Consistent group showed poor performance on rhyme and alliteration but appropriate performance on syllable segmentation. The Inconsistent group performed most poorly on syllable segmentation but no differently from controls on the other two tasks. The second study indicated that children with a history of inconsistent phonological disorder performed no differently from controls on measures of phonological awareness and reading, but less well on measures of spelling ability. CONCLUSIONS: The results support classification of speech disorders and show a differentiation of phonological awareness skills across groups. Children with consistent atypical speech errors have poor phonological awareness and are most at risk for literacy difficulties. Those with inconsistent phonological disorder are at increased risk of spelling difficulties. The findings indicate that phonological awareness and spelling skill are distinct processing systems and highlight the role of phonological assembly skills (i.e. storing and/or retrieving phonological output plans) in spelling output. The interactive processes between reading and spelling are discussed. PMID- 17852520 TI - Grounded theory as a method for research in speech and language therapy. AB - BACKGROUND: The use of qualitative methodologies in speech and language therapy has grown over the past two decades, and there is now a body of literature, both generally describing qualitative research, and detailing its applicability to health practice(s). However, there has been only limited profession-specific discussion of qualitative methodologies and their potential application to speech and language therapy. AIM: To describe the methodology of grounded theory, and to explain how it might usefully be applied to areas of speech and language research where theoretical frameworks or models are lacking. METHODS & PROCEDURES: Grounded theory as a methodology for inductive theory-building from qualitative data is explained and discussed. Some differences between 'modes' of grounded theory are clarified and areas of controversy within the literature are highlighted. The past application of grounded theory to speech and language therapy, and its potential for informing research and clinical practice, are examined. MAIN CONTRIBUTION: This paper provides an in-depth critique of a qualitative research methodology, including an overview of the main difference between two major 'modes'. The article supports the application of a theory building approach in the profession, which is sometimes complex to learn and apply, but worthwhile in its results. CONCLUSIONS: Grounded theory as a methodology has much to offer speech and language therapists and researchers. Although the majority of research and discussion around this methodology has rested within sociology and nursing, grounded theory can be applied by researchers in any field, including speech and language therapists. The benefit of the grounded theory method to researchers and practitioners lies in its application to social processes and human interactions. The resulting theory may support further research in the speech and language therapy profession. PMID- 17852521 TI - Children with specific language impairment: an investigation of their narratives and memory. AB - BACKGROUND: Narratives have been used by a number of researchers to investigate the language of children with specific language impairment (SLI). While a number of explanations for SLI have been proposed, there is now mounting evidence that children with SLI have limited memory resources. Phonological memory has been the focus of the research on memory with this population. However, the use of narrative tasks to investigate memory limitations in SLI has not previously been undertaken. AIMS: The aims of the research were to investigate the narrative and memory abilities of 6-year-old children with SLI and the association between narrative skills and memory. METHODS & PROCEDURES: Two studies were conducted. In Study 1 the performance of the children with SLI was compared with that of their peers with typical language development (AM), and to that of a younger group (LM) matched on expressive language (about 2 years younger). Children were asked to recall ('story recall') and show comprehension of a narrative they had been told, and also to tell a story based on a series of pictures ('story generation'), to recall their story and to answer comprehension questions about it. In Study 2 the children with SLI from Study 1 and the AM children from Study 1 were tested on four working memory tasks: word and digit span, the Recalling Sentences task from the Clinical Evaluation of Language Fundamentals--Third Edition, and a dual processing task. An inhibition task and an attention task were also included. It was predicted that children with SLI would perform more poorly than the AM group on measures of narrative telling, but comparably with the LM group. It was also predicted that the SLI group would perform more poorly than the AM group on both literal and inferencing comprehension questions but comparably with the LM group. The third prediction was that there would be significant associations between children's performance on the narrative tasks and the tasks measuring working memory. OUTCOMES & RESULTS: In Study 1 the children with SLI performed more like the younger group on recall of a narrative they had heard, but more like their peers when asked to generate and recall their own narrative based on a series of pictures. The children with SLI had difficulty with inferencing questions. In Study 2 the impaired group performed significantly worse on measures of memory, showing a lower working memory capacity. The children with SLI made more errors on the attention task, but no group differences were found on the inhibition task. In comparing results from Studies 1 and 2, significant correlations were found between performance on the narrative tasks and memory tasks, but the contribution of memory to the narrative task scores differed for the two stories. The Recalling Sentences memory task was found to be the best overall measure for predicting variance on story comprehension and recall. CONCLUSIONS: In support of previous research, the children with SLI showed problems with inferencing, linking directly observed or stated information to likely outcomes. They also showed a limited working memory capacity, and they were more likely to make errors in attention. A main finding was that the narrative abilities of the 6 year-old children were linked to their verbal working memory. The information the SLI group heard was harder to access than information they had been able to generate themselves based on a series of pictures. The findings suggest that children with SLI are likely to be at a disadvantage in classroom situations, particularly for information presented aurally and if the information is complex. The use of pictorial aids may help them encode the information. They would also benefit from having information broken into manageable units. PMID- 17852522 TI - Visuo-spatial processing and executive functions in children with specific language impairment. AB - BACKGROUND: Individual differences in complex working memory tasks reflect simultaneous processing, executive functions, and attention control. Children with specific language impairment (SLI) show a deficit in verbal working memory tasks that involve simultaneous processing of information. AIMS: The purpose of the study was to examine executive functions and visuospatial processing and working memory in children with SLI and in their typically developing peers (TLD). Experiment 1 included 40 children with SLI (age = 5; 3-6;10) and 40 children with TLD (age = 5; 3-6;7); Experiment 2 included 25 children with SLI (age = 8;2-11; 2) and 25 children with TLD (age = 8; 3-11; 0). It was examined whether the difficulties that children with SLI show in verbal working memory tasks are also present in visuo-spatial working memory. METHODS & PROCEDURES: In Experiment 1, children's performance was measured with three visuo-spatial processing tasks: space visualization, position in space, and design copying. The stimuli in Experiment 2 were two widely used neuropsychological tests: the Wisconsin Card Sorting Test-64 (WCST-64) and the Tower of London test (TOL). OUTCOMES & RESULTS: In Experiment 1, children with SLI performed more poorly than their age-matched peers in all visuo-spatial working memory tasks. There was a subgroup within the SLI group that included children whose parents and teachers reported a weakness in the child's attention control. These children showed particular difficulties in the tasks of Experiment 1. The results support Engle's attention control theory: individuals need good attention control to perform well in visuo-spatial working memory tasks. In Experiment 2, the children with SLI produced more perseverative errors and more rule violations than their peers. CONCLUSIONS: Executive functions have a great impact on SLI children's working memory performance, regardless of domain. Tasks that require an increased amount of attention control and executive functions are more difficult for the children with SLI than for their peers. Most children with SLI scored either below average or in the low average range on the neuropsychological tests that measured executive functions. PMID- 17852523 TI - Sentence production in students with dyslexia. AB - BACKGROUND: While spoken language deficits have been identified in children with developmental dyslexia, microanalysis of sentence production proficiency in these children is a largely unexplored area. AIMS: The current study examines proficiency of syntactic production in children and young adults with dyslexia and typically developing age-matched controls on a constrained sentence production task targeting two advanced argument structures, theme-experiencer verbs and irregular past participles. METHODS & PROCEDURES: Participants aged between 8 and 22 years produced sentences that included three stimulus words, a proper name, an inanimate noun and a verb from one of three categories: control verbs (agent-patient verbs with regular morphology); theme-experiencer verbs, which require an inanimate subject in active sentences (e.g. The book bored Sarah); and irregular past participles, which require awareness of the syntactic requirements associated with the -en past participle ending, i.e. that this verb form cannot be used as a simple past tense (e.g. *Mary ___ hidden the candy). OUTCOMES & RESULTS: Students with dyslexia produced more dysfluent, ungrammatical and incomplete responses than normal readers; however, the developmental trajectories of the verb types varied between groups. Normal readers performed similarly with both experimental verb types, but those with dyslexia were particularly impaired using irregular past participles in sentences. CONCLUSIONS: The findings support a model of lexical representation in which development of grammar hinges on the acquisition of lexical knowledge. Furthermore, the data suggest that individuals with dyslexia may have difficulties with sentence formulation that persist into adulthood. PMID- 17852524 TI - Intervention for lateral /s/ using electropalatography (EPG) biofeedback and an intensive motor learning approach: a case report. AB - BACKGROUND: Visual biofeedback using electropalatography (EPG) has been beneficial in the treatment of some cases of lateral /s/ misarticulation. While EPG intervention is motorically based, studies have not commonly employed a motor learning approach to treatment. Furthermore, treatment success is measured primarily by change to EPG tongue-palate contact patterns and listener ratings conducted by speech-language therapists. Studies have not commonly measured articulatory change without the palate in-situ using acoustic analysis and non professional listeners. AIMS: To determine if an intensive treatment programme including both visual biofeedback (EPG) and traditional articulation techniques within a motor learning paradigm would result in functional improvement to /s/ articulation in an 11-year-old girl with persistent lateral misarticulation. METHODS & PROCEDURES: Treatment involved 12 sessions of therapist-delivered treatment over 4 weeks followed by a 6-week home programme. Outcomes of the treatment programme were measured primarily using naive listener ratings and acoustic analysis of /s/ spectra. OUTCOMES & RESULTS: Improvements to both the perceptual and spectral characteristics of /s/ articulation occurred following the treatment programme. CONCLUSIONS: The study highlighted the benefit of an intensive approach to intervention incorporating both visual biofeedback and traditional articulation approaches. The inclusion of a 6-week structured home programme was beneficial and resulted in consolidation of treatment gains. PMID- 17852525 TI - Exploring the implementation and use of outcome measurement in practice: a qualitative study. AB - BACKGROUND: Outcome measurement is important to clinical practice--yet outcome many speech and language therapists find it difficult to apply measures in practice, and not all clinicians and services have been able to implement and/ or use outcome measurement successfully. To date there has been little research to explain why implementation is often unsuccessful, and to provide clinicians and managers with direction as to the likely barriers and facilitators which should be considered. AIMS: To develop a theoretical framework to explain the implementation and use of outcome measurement in clinical practice by speech and language therapists. METHODS & PROCEDURES: A qualitative, inductive theory building approach, using grounded theory methodology, was applied. This included theoretical sampling, constant comparison, memo writing, and theoretical integration. Participants were 16 Australian managers and clinicians who were using, or who had used, outcome measures. OUTCOMES & RESULTS: The resulting theoretical framework explains two interactive stages that occur when speech pathologists attempt to use outcome measurements in practice. First, clinicians must 'try on' outcome measurement in their own context, examining the way it fits with existing areas, such as their normal practices and priorities, and the wider group and organizational context. Having identified where outcome measurement does not 'fit', clinicians attempt to 'align' outcome measurement with the context (or vice versa), in order to create a better fit between the two. Strategies of 'tailoring' outcome measurement (e.g. using only parts of a measure) or 'accommodating' outcome measurement (e.g. changing routines to allow time for outcome measurement ratings) are possible, but are dependent on clinicians having a true picture of outcome measurement, the role and need for the data, and the existing context. Clinicians must also have control over the areas that need to change in order for outcome measurement and the context to 'align'. Where outcome measurement and the context can be aligned, outcome measures are more easily used. CONCLUSIONS: The theory provides a framework for considering the use of outcome measurement in clinical practice. Implications for implementing outcome measurement in clinical practice are discussed, including the need to clarify the role and need for the data; the requirement that clinicians understand how outcome measurement fits with context outside of their own personal purview; and the need for managers to support change to areas that are outside of the control of clinicians. PMID- 17852526 TI - Relationship between perceptual ratings of nasality and nasometry in children/adolescents with cleft palate and/or velopharyngeal dysfunction. AB - BACKGROUND: Nasometry has supplemented perceptual assessments of nasality, using speech stimuli, which are devoid of nasal consonants. However, such speech stimuli are not representative of conversational speech. A weak relationship has been found in previous studies between perceptual ratings of hypernasality and nasalance scores for passages containing nasal consonants. AIMS: This study aimed to evaluate the relationship between perceptual assessment and acoustic measurements of nasality using controlled speech stimuli. METHODS & PROCEDURE: A perceptual scale (the Temple Street Scale) describing nasality was devised for this study. Fifty children presenting with nasality were assessed using the Temple Street Scale and nasalance scores were obtained for specified speech samples using the Nasometer (Kay Elemetrics 6200.3). The relationship between the perceptual ratings and the nasometry results was evaluated using correlation analysis, test sensitivity, specificity, and overall efficiency. OUTCOMES & RESULTS: Correlation coefficients for perceptual ratings of nasality and nasalance scores ranged from 0.69 to 0.74. The sensitivity of the Nasometer ranged from 0.83 to 0.88; its specificity ranged from 0.78 to 0.95; while its overall efficiency was between 0.82 and 0.92. CONCLUSIONS: The strong relationship between perceptual and acoustic assessments of nasality indicated that the Temple Street Scale and the Nasometer are both valid clinical tools for the evaluation of nasality when a carefully constructed speech sample is used. The need to use the Nasometer as a supplement to perceptual assessment is highlighted. PMID- 17852527 TI - Case study using ultrasound to treat /r/. AB - BACKGROUND: Ultrasound has shown promise as visual feedback in remediation of /r/. AIMS: To compare treatment for /r/ with and without ultrasound. METHODS & PROCEDURES: A Canadian English-speaking adolescent participated in a case study with a no treatment baseline, alternating treatment blocks with and without ultrasound and a final no treatment period. OUTCOMES & RESULTS: Formant values and trained listener ratings of speech samples indicated improvement in /r/ production, particularly after the introduction of ultrasound. CONCLUSIONS: Ultrasound appeared to facilitate the acquisition of /r/ for the participant. Large-scale studies are needed to evaluate ultrasound further. PMID- 17852530 TI - Concordance rates between parent and teacher clinical evaluation of language fundamentals observational rating scale. AB - BACKGROUND: Research has shown that early identification of children with language issues is critical for effective intervention, and yet many children are not identified until school age. The use of parent-completed rating scales, especially in urban, minority populations, might improve early identification if parent ratings are found to be reliable and valid. AIMS: To evaluate the reliability and validity of the Observational Rating Scale (ORS) in an urban setting where it may be difficult to distinguish language difficulties from cultural language differences. METHODS & PROCEDURES: The present study examined the degree to which parent and teacher ORS scores for 73 7-10-year-old children (47 boys) had concordance for the four ORS dimensions of Listening, Speaking, Reading, and Writing, as well as for a composite ORS score. The relationship between the ORS ratings and the children's scores on the CELF-3, or CELF-4 Receptive and Expressive scores, and the WIAT Reading Composite scores were also examined. OUTCOMES & RESULTS: Parent and teacher concordance rates for the ORS were significant, but moderate for the Speaking, Reading, and Writing categories and for the overall ORS score. There were also significant relationships between the ORS scores and performance on standardized language and reading tests supporting the validity of the ORS. CONCLUSIONS: The reliability and validity of the ORS have been replicated and extended to a diverse, urban population. Further, parent ratings were shown to provide as least as good information about language function as teacher ratings. Finally, it was suggested that an overall ORS score may provide a better indicator of overall language function than the domain scores. PMID- 17852531 TI - Development and preliminary validation of a measure for assessing staff perspectives on the quality of clinical group supervision. AB - BACKGROUND: In the UK clinical supervision is regarded as an essential process supporting quality improvement within the clinical governance framework, and the Royal College of Speech and Language Therapists regards it as a tool for promoting critical reflective practice. There is limited evidence of the impact on practice or improvements in healthcare quality, and the need for an evaluation instrument specifically tailored to group supervision. AIMS: To develop a measure for assessing staff perspectives on the quality of clinical group supervision and its impact on the quality of care. METHODS & PROCEDURES: A self-completion questionnaire was devised to measure staff perceptions of purpose, process and impact of clinical group supervision. Items were developed through an inductive process of consultation, peer and literature review. The questionnaire's content validity was assessed. The questionnaire was then administered to 57 subjects who had received approximately 1 year of clinical supervision to evaluate acceptability, factor structure and convergent validity. OUTCOMES & RESULTS: Response rates were 91% (52/57). Principal component factor analysis suggested a three-factor structure, the first three factors accounting for 72.4% of the total variance. Items loaded appropriately onto purpose, process and impact. These three dimensions were positively and moderately correlated. Internal consistency reliability (Cronbach's alpha = 0.86) indicated that the 14 items could be regarded as a scale. The overall CSEQ score was positively correlated with a single question assessing 'general opinion' about the CS program (Spearman's rho = 0.79, p < 0.001) giving evidence for convergent validity. CONCLUSIONS: The questionnaire is concise, easy to complete and simple to analyse, and appears to be a reliable and valid measure of staff perceptions of quality of clinical group supervision. Further studies with larger sample sizes and including other groups of health professionals are needed to confirm the validity and reliability of the CSEQ. PMID- 17852532 TI - Comparing phonological skills and spelling abilities in children with reading and language impairments. AB - BACKGROUND: Bishop and Snowling (2004) proposed that children with language impairments (LI) and children with reading difficulties (RD) can be considered to be on a (phonological) continuum of risk for reading impairments. AIMS: The first aim of the present study was to address two specific hypotheses about the relationship between RD and LI. The severity hypothesis proposes that LI is a more severe form of RD. In contrast, the dyslexia-plus hypothesis proposes that children with LI share the same phonological deficit as children with RD, but also have impairments in non-phonological language skills. The second aim of the study was to further our understanding of the spelling skills of children with LI. METHODS & PROCEDURES: Twenty-three children with primary language impairments (LI) and 22 children with primary reading impairments (RD) matched on chronological and reading age were compared with typically developing children. The children's performance on tests of phoneme deletion, phonological memory, and spelling accuracy and phonetic spelling was compared. OUTCOMES & RESULTS: Children with LI showed poorer phonological memory performance than children with RD and age controls, whereas both clinical groups performed significantly worse than the age controls on the phoneme deletion task and comparably to reading-age controls. Children with LI and RD were impaired for their age at phonetic spelling, the children with LI showing the more severe impairment. Further exploration of the data identified two different profiles among children with LI; some of these children had poorer phonological skills than predicted from receptive vocabulary, supporting the severity hypothesis. The other group showed a profile with concurrent impairments in vocabulary and phonological skills, in line with the dyslexia-plus hypothesis. CONCLUSIONS: The findings suggest that a subgroup of children with LI may be experiencing a severe form of dyslexia. The results further suggest that children with LI have difficulty producing phonologically plausible spellings. PMID- 17852533 TI - 'Communication is everything I think.' Parenting a child who needs Augmentative and Alternative Communication (AAC). AB - BACKGROUND: Anecdotal and research evidence suggests that professionals may not fully understand the perspectives of families of children who need or use Augmentative and Alternative Communication (AAC). This may impact on the provision of appropriate services. AIMS: The aim was to explore the lived experience of parents of children in Britain who used AAC, with particular emphasis on the ways in which children's need for and use of AAC impacts on family life and communication. METHODS & PROCEDURES: The parents/carers of 11 children aged 3-10 years, who lived in Britain and who were in the early stages of using AAC, were recruited to take part in the study. Individual semi structured interviews were carried out in order to access rich descriptions of parents' experiences and views about having children who need to use AAC. The interviews were recorded, transcribed verbatim and analysed thematically to generate thematic networks. OUTCOMES & RESULTS: Analysis revealed three thematic networks. The three Global Themes represented by the networks were concerned with the following areas: the child's communication and interaction; wider societal issues; and parents' views and experiences. Each Global Theme contained lower order Organizational Themes and these in turn were comprised of Basic Themes. Parents shared many common concerns, but the data also revealed some diversity of views. The themes and sub-themes are described with illustrative and representative quotes. CONCLUSIONS: These parents are experts on their children and may also be experts on AAC. Many factors impact on parents and the level and type of involvement they have with their children and their upbringing. Speech and language therapists need to acknowledge parents' knowledge and expertise regarding their children. They need to recognize that there are parent, child, family and external factors which impact on parents' ability and willingness to be involved in speech and language therapist provision, and that these factors are not static over time. The use of ethnographic interviewing techniques should be considered a valuable aspect of speech and language therapist intervention. PMID- 17852534 TI - Thai Speech and Language Test for children between 1 and 2 years of age. AB - BACKGROUND: Children with delayed speech and language development are at considerable risk for later language impairment, social and behavioural problems, and illiteracy. Early diagnosis is needed for intervention planning and prevention. However, a speech and language test for Thai children has not been available. AIMS: To establish a Thai Speech and Language Test for Thai children between zero and 2 years of age. METHODS & PROCEDURES: The authors reviewed both Thai and international speech and language development tests and studies related to factors associated with speech and language development. A Thai Speech and Language Test for children between zero and 2 years of age (TSLT2) was then formulated. The test was used with 419 typically developing Thai children in Khon Kaen, north-east Thailand. OUTCOME & RESULTS: Language quotients were calculated to quantify/qualify Thai language development norms. Inter-rater reliability of the test ranged between 0.64 and 1, while internal consistencies ranged between 0.83 and 0.95 for tests on children between 1 and 2 years of age. CONCLUSIONS: Professionals or paraprofessionals can use the Thai Speech and Language Test for children between 1 and 2 years of age, which is the first Thai tool for the assessment, diagnosis and remediation planning of children with delayed speech and language development. It should be also adapted for use in other regions in Thailand. However, the test for children aged between 3 and 9 months should be revised and continue to be developed. PMID- 17852535 TI - Mapping practice onto theory: the speech and language practitioner's construction of receptive language impairment. AB - BACKGROUND: Receptive language impairment (RLI) is one of the most significant indicators of negative sequelae for children with speech and language disorders. Despite this, relatively little is known about the most effective treatments for these children in the primary school period. AIMS: To explore the relationship between the reported practice of speech and language practitioners and the underlying rationales for the therapy that they provide. METHODS & PROCEDURES: A phenomenological approach was adopted, drawing on the experiences of speech and language practitioners. Practitioners completed a questionnaire relating to their practice for a single child with receptive language impairment within the 5-11 age range, providing details and rationales for three recent therapy activities. The responses of 56 participants were coded. All the children described experienced marked receptive language impairments, in the main associated with expressive language difficulties and/or social communication problems. OUTCOME & RESULTS: The relative homogeneity of the presenting symptoms in terms of test performance was not reflected in the highly differentiated descriptions of intervention. One of the key determinants of how therapists described their practice was the child's age. As the child develops the therapists appeared to shift from a 'skills acquisition' orientation to a 'meta-cognitive' orientation, that is they move away from teaching specific linguistic behaviours towards teaching children strategies for thinking and using their language. A third of rationales refer to explicit theories but only half of these refer to the work of specific authors. Many of these were theories of practice rather than theories of deficit, and of those that do cite specific theories, no less than 29 different authors were cited many of whom might best be described as translators of existing theories rather than generators of novel theories. CONCLUSIONS: While theories of the deficit dominate the literature they appear to play a relatively small part in the eclectic practice of speech and language therapists. Theories of therapy may develop relatively independent of theories of deficit. While this may not present a problem for the practitioner, whose principal focus is remediation, it may present a problem for the researcher developing intervention efficacy studies, where the theory of the deficit will need to be well-defined in order to describe both the subgroup of children under investigation and the parameters of the deficit to be targeted in intervention. PMID- 17852536 TI - Individual variation in agrammatism: a single case study of the influence of interaction. AB - BACKGROUND: Agrammatic speech can manifest in different ways in the same speaker if task demands change. Individual variation is considered to reflect adaptation, driven by psycholinguistic factors such as underlying deficit. Recently, qualitative investigations have begun to show ways in which conversational interaction can influence the form of an agrammatic speaker's output. AIMS: To explore qualitative patterns of individual variation in the output of a single case, in order to address the following questions: (1) in what ways do grammatical structure, verbs and argument structure differ qualitatively between data samples?; and (2) what is the influence of interaction on the structure of utterances? METHODS & PROCEDURES: A man with severe and chronic agrammatism is videotaped completing tests of spoken sentence construction, composite, and cartoon strip picture descriptions and a story telling task. In addition, he independently videotapes a sample of conversation with a family member at home. Analyses of these data draw on cognitive neuropsychological, linguistic and psycholinguistic methodologies as well as the data-driven procedures of conversation analysis. OUTCOMES & RESULTS: The qualitative analysis uncovers considerable variation between data sets with respect to grammatical structure, verbs and argument structure. The agrammatic speaker appears more skilled at imposing order on his spontaneous speech than the results of sentence construction tests might predict. Interaction influences his output style. Adaptation is found to be a collaborative process that occurs between two speakers in the quest for mutual understanding, not something that takes place within an individual. CONCLUSIONS: It is concluded that an interactional approach to agrammatism has the potential to yield important insights into the characteristics of telegraphic speech and individual variation. The failure of sentence-level tests to capture this individual's skill in producing systematically structured utterances in conversation implies that the assessment of agrammatism could benefit from the additional sampling and analysis of conversational grammar. PMID- 17852537 TI - Comprehension problems in children with specific language impairment: does mental imagery training help? AB - BACKGROUND: Children with specific language impairment experience story comprehension deficits. Research with typically developing children, poor comprehenders and poor readers has shown that the use of mental imagery aids in the comprehension of stories. AIMS: To evaluate the effectiveness of an intervention programme in the use of mental imagery to improve the literal and inferential comprehension of children with specific language impairment. METHODS & PROCEDURES: Nine children with specific language impairment were trained to produce mental images for sentences and stories in five 30-min sessions. Their ability to answer literal and inferential questions about short narratives was assessed pre- and post-intervention and compared with the performance of 16 same age typically developing controls. OUTCOME & RESULTS: The intervention improved the question-answering performance of the children with specific language impairment for both literal and inferential questions: the improvement was only significant for the literal questions. CONCLUSIONS: The findings demonstrate that a relatively short intervention in the use of mental imagery is an effective way to boost the story comprehension of children with specific language impairment. PMID- 17852538 TI - Lingual kinematics and coordination in speech-disordered children exhibiting differentiated versus undifferentiated lingual gestures. AB - BACKGROUND: Electropalatographic investigations have revealed that a proportion of children with articulation/phonological disorders exhibit undifferentiated lingual gestures, whereby the whole of the tongue contacts the palate simultaneously during lingual consonant production. These undifferentiated lingual gestures have been interpreted to reflect a 'motor constraint', with the tongue tip and body incapable of operating independently. AIMS: The present study aimed to provide further insight into the speech motor control abilities of children with articulation/phonological disorders by using electromagnetic articulography to track the movements (velocity, acceleration, distance, duration) of, and the coordination between, the tongue tip and tongue body during lingual consonant production. METHODS & PROCEDURES: Comparisons were made between two children with persistent articulation/phonological disorders who exhibited differentiated electropalatographic gestures (9.58 and 10 years), one child with persistent articulation/phonological disorder who demonstrated undifferentiated lingual gestures (11 years), and a group of four control children (mean age=10.98 years, standard deviation=0.48). The children were asked to read aloud single syllable words containing word-initial /t, s, k/ consonants, with tongue tip and tongue body movements recorded using the electromagnetic articulography AG200 system (Carstens Medizinelektronik GmbH, Germany). OUTCOMES & RESULTS: Kinematic analysis revealed increased kinematic values for /s/ for the two children with articulation/phonological disorders and differentiated electropalatographic gestures compared with the control group. One of these children also exhibited increased /k/ duration. Reduced acceleration was exhibited by one child with differentiated electropalatographic gestures during /t/ production, and by the child with undifferentiated lingual gestures during /k/. Regarding coordination, lag times between the tongue tip and body were variable between and within children. Spatial contribution to consonant production discriminated between the children with differentiated electropalatographic gestures and undifferentiated lingual gestures, with excessive movement of the tongue body exhibited for alveolar consonants by the child with undifferentiated lingual gestures. CONCLUSIONS: All three of the children with articulation/phonological disorders demonstrated aberrant lingual kinematics. The child who exhibited undifferentiated lingual gestures further exhibited excess tongue body movement during alveolar consonants, suggestive of poor motor control, an immature or deviant bracing system, and/or a compensatory mechanism to counteract potential disturbances in tongue tip fine motor control. Electromagnetic articulography provided a means of examining speech motor control deficits, including disturbances in tongue movement and coordination, in children with articulation/phonological disorders. PMID- 17852539 TI - Reliability of speech diadochokinetic test measurement. AB - BACKGROUND: Measures of articulatory diadochokinesis (DDK) are widely used in the assessment of motor speech disorders and they play a role in detecting abnormality, monitoring speech performance changes and classifying syndromes. Although in clinical practice DDK is generally measured perceptually, without support from instrumental methods that display the acoustic waveform, no standard measurement procedures are employed and studies on inter- and intra-rater reliability are lacking. AIMS: To investigate the inter- and intra-rater reliability of perceptual DDK measurement and the possible impact of experience on rating performance. METHODS & PROCEDURES: Ten speech and language therapists and ten untrained controls rated 12 DDK speech samples, including two pairs of identical samples, of speakers with different neurological speech disorders. We compared timing for repetitions as close as possible to 5 s, for 5 s exactly, and for as long as the speaker could manage; as well as four qualitative features (rhythm, distinctness, loudness and overall impression). Counts by time were compared with objective outcomes from sound spectrograms. OUTCOMES & RESULTS: Inter- and intra-rater reliability was lower than should be acceptable for clinical diagnostic and outcome assessment. The most accurate and repeatable procedure (compared with objective measurement) was counting the syllables within the first 5 s. There was no unequivocal influence of clinical experience on accuracy. CONCLUSIONS: The findings suggest caution in employing and interpreting clinical DDK measures as diagnostic and outcome measures. More research is necessary to settle the influence of experience on time and count accuracy and what modifications to timing might bring increased agreement that permits DDK to realize its full potential in assessment. PMID- 17852540 TI - Site -2548 of the leptin gene is associated with gender-specific trends in newborn size and cord leptin levels. AB - OBJECTIVE: Circulating leptin levels positively correlate with adult BMI and size at birth. Previous studies found gender-specific associations between polymorphisms in the leptin gene and postnatal obesity-related traits or circulating leptin levels. We examined the relationships among leptin gene polymorphisms, size for gestational age, umbilical cord leptin, and gender. METHODS: Six single nucleotide polymorphisms (SNPs) were genotyped in the leptin gene in 261 newborns (72 low birth weight Caucasians, 189 randomly-selected African-Americans). In African-Americans, umbilical cord leptin and free testosterone levels were measured. Linear regression was used to identify significant predictors of size for gestational age or cord leptin levels and gender x genotype interaction effects. RESULTS: There is a significant interaction between gender and genotype at site -2548 (A/G). Among low birth weight Caucasians, the A allele was associated with an increase in female size for gestational age, while the A allele was associated with decreased male birth size. Among African-Americans, the A allele was associated with a decrease in umbilical cord leptin in females and with an increase in cord leptin in males. Cord testosterone levels were not a significant predictor of cord leptin levels either among all African-American newborns or among strata of -2548 genotypes and gender. CONCLUSION: In male and female fetuses, site -2548 of the leptin gene may differently affect the expression level of the leptin gene or the rate of fetal growth. This gender-specific effect does not appear to be mediated by the level of free testosterone at delivery. PMID- 17852541 TI - Resting energy expenditure, adiponectin and changes in body composition of young children (EarlyBird 34). AB - OBJECTIVE. Serum adiponectin levels are inversely related to adiposity and resting energy expenditure (REE) in adults yet may protect against excess weight gain. Little is known of these associations in children, in whom obesity is rising. The aim of this study was therefore to investigate the relationships between REE, adiponectin and weight gain in young children. METHODS. Adiponectin by ELISA, REE by indirect calorimetry, fat-free mass (FFM) and fat mass (FM) by DEXA were measured at 6.9 years, and repeated one year later in 151 healthy children, aged 7.9+/-0.3 years. RESULTS. There were no significant correlations between REE and adiponectin at 6.9 years or at 7.9 years (boys r=-0.02, p=0.88 and r=0.05, p=0.69, respectively; girls r=-0.11, p=0.35 and r=0.05, p=0.70, respectively). There was no link between REE at 6.9 years and subsequent weight gain or adverse change in body composition (all r<0.20, all p>0.08). Similarly, there were no correlations between adiponectin and weight change, but there was a significant inverse association between adiponectin at 6.9 years and FFM gain in boys (r=-0.27, p=0.02). CONCLUSIONS. The relationship between adiponectin and REE has yet to appear in young children. REE is not a significant predictor of future weight gain or adverse change in body composition and, although the period of follow-up was limited, adiponectin seems unlikely to confound such a relationship in healthy young children. PMID- 17852542 TI - Validity of thoracic gas volume equations in children of varying body mass index classifications. AB - OBJECTIVE: The aim of the study was to evaluate air-displacement plethysmography (ADP) thoracic gas volume (TGV) prediction equations in children representing a wide range of body mass index (BMI). METHODS: 254 children (5 to 17 years) were recruited from two centres (England and the United States). Subjects were stratified into three BMI categories according to the International Obesity TaskForce (IOTF) criteria: lean (48 male, 42 female), overweight (15 male, 29 female), and obese (52 male, 68 female). As part of the normal ADP procedure, TGV was measured (TGV(Meas)), predicted using child specific equations developed by Fields (TGV(Fields)) and adult derived equations by Crapo (TGV(Crapo)) with percentage body fat (PF) estimates subsequently calculated (PF(Meas), PF(Fields), PF(Crapo)). RESULTS: Compared with the mean TGV(Meas), the TGV(Fields) estimates were within+/-0.2 L in all groups, except obese males (+0.5 L), while the mean TGV(Crapo) estimates were greater than+/-0.3 L in all groups except lean males (+0.1 L). When converted to PF, the mean PF(Fields) estimates were within+/-1% of the measured value in all groups, except obese males (+1.1%), while the mean PF(Crapo) estimates were greater than+/-1% in all groups, except lean males (+0.5%). Using either prediction equation, Bland-Altman analysis revealed that the greatest PF+/-95% limits of agreement were in the lean and overweight groups and lowest in the obese groups. CONCLUSION: The Fields child-specific TGV prediction equations provide accurate mean PF estimates and appear better than using the Crapo equations if a measured TGV cannot be achieved in children of a wide range of BMI. However, individual predictions may result in large PF errors especially in lean children. PMID- 17852543 TI - US Food assistance programs and trends in children's weight. AB - OBJECTIVES. High rates of overweight and obesity among low-income children have led some to question whether participation in US domestic food assistance programs contributes to this health problem. We use multiple years of data to examine trends in children's body weight and participation in the Food Stamp Program (FSP) or Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). Specifically, we assess whether a consistent relationship between program participation and body weight exists over time. METHODS. Data from multiple waves of the National Health and Nutrition Examination Surveys (NHANES) are used to examine the relationship between children's body weight and food assistance programs between 1976 and 2002. Linear regression models are used to estimate BMI and logit models are used to predict the probabilities of at-risk of overweight and overweight. Food assistance program participants (either FSP or WIC participants depending on age) are compared with income eligible non participants and higher income children. RESULTS. Results show no systematic relationship over time between FSP participation and weight status for school aged children (age 5-17). For children aged 2-4, no differences in weight status between WIC participants and eligible non-participants were found. However, recent data show some differences between WIC participants and higher income children. CONCLUSIONS. Our analysis does not find evidence of a consistent relationship between childhood obesity and participation in the FSP or WIC programs. PMID- 17852544 TI - The prevalence of leisure time sedentary behaviour and physical activity in adolescent girls: an ecological momentary assessment approach. AB - STUDY OBJECTIVE: To use ecological momentary assessment to describe how adolescent girls in the United Kingdom spend their leisure time. DESIGN: Cross sectional, stratified, random sample from secondary schools in 15 regions within the United Kingdom. The data are from a larger study of adolescent lifestyles (Project STIL). PARTICIPANTS: A total of 923 girls with a mean age of 14.7 years (range 12.5-17.6 years). The majority were white-European (88.7%). MAIN RESULTS: Across all behaviours, television viewing occupied the most leisure time on both weekdays and weekend days. The five most time consuming sedentary weekday activities occupied on average 262.9 minutes per weekday and 400 minutes per weekend day. In contrast, only 44.2 minutes was occupied by active transport or sports and exercise per weekday, and 53 minutes per weekend day. Only a minority watched more than 4 hours of TV per day (3.3% on weekdays and 20.7% on weekend days). Computer use is low in this group. Some differences were noted in the means and prevalences between weekend and weekdays, most likely reflecting the greater discretionary time available at the weekend. Few age differences were noted. CONCLUSIONS: Adolescent girls engage in a variety of behaviours that contribute to an overall lifestyle that may be active or sedentary. Effective physical activity promotion strategies must focus on facilitating shifts towards healthy overall patterns of behaviour rather than shifts in any one single behaviour. PMID- 17852545 TI - Overweight and obesity are rapidly emerging among adolescents in Ho Chi Minh City, Vietnam, 2002-2004. AB - OBJECTIVE: To assess changes in the prevalence of overweight and obesity among adolescents in urban districts of Ho Chi Minh City between 2002 and 2004. METHODS: Two surveys were conducted among high school students (11-16 years) in 2002 (n = 1003 students) and 2004 (n = 2684). International Obesity Taskforce (IOTF) sex and age specific BMI cut-offs were used to define overweight and obesity. Underweight was defined as a BMI-for-age z-score <-2, based on the US Centers for Disease Control and Prevention (CDC) 2000 growth reference. In 2002, students completed a questionnaire about household assets. In 2004, parents answered questions about their weight, height, education, occupation, and ownership of 14 household assets. RESULTS: The prevalence of overweight and obesity increased from 5.0% and 0.6% in 2002, to 11.7% and 2.0% in 2004, respectively (p<0.001), while the prevalence of underweight decreased from 13.1% to 6.7%. There was a significant increase in prevalence of overweight and obesity by gender over the two years: the 113% increase in prevalence of overweight and obesity in boys was significantly greater than the 39% increase in girls (p<0.001). The percentage increase in overweight and obesity was considerably lower in adolescents from the poorest households (33%), than from the other quintiles of wealthier households (ranging from 77% to 124%) (p<0.001). CONCLUSIONS: The prevalence of overweight and obesity among adolescents in Ho Chi Minh City is increasing rapidly. There is an urgent need to implement strategies for prevention and control amongst the adolescents of Ho Chi Minh City and other urban areas in Vietnam. PMID- 17852546 TI - Foot structure in overweight and obese children. AB - OBJECTIVE. To analyse the association between overweight and obesity and foot structure in children older than 9 years of age, whose longitudinal medial arch (MLA) should be practically established. DESIGN, SETTING AND SUBJECT. A cross sectional study of 245 children (age: 13.22+/-1.8 years) from four randomly selected schools (Zaragoza, Spain). Body mass index (BMI) was calculated and normal-weight, overweight and obese groups were defined. Footprints for both feet were collected. MEASUREMENTS. Foot angle (FA) and Chippaux-Smirak index (CSI) were calculated from the footprints. Height and body mass were measured to calculate the BMI. RESULTS. Mean values of FA and CSI in the normal-weight group indicated the presence of a normal MLA; however, in the overweight they indicated an intermediary MLA and in the obese group, a low MLA. Comparison among the groups showed a decrease of FA (p<0.01) and an increase of CSI (p<0.01) with increasing weight associated with a lower MLA. A low but significant correlation (p<0.0001) was found between the z-score BMI and footprint parameters. CONCLUSIONS. In children aged 9 to 16.5 years, the increase of body mass is related to a lower MLA. The MLA is lower in these obese children than in the younger ones studied in previous works probably due to the continuous bearing of excessive mass from childhood. A lower MLA could cause health problems. An assessment of foot structure in these children is recommended as the classification of the foot arch type can help decide if treatment to avoid these problems is necessary. PMID- 17852547 TI - The effects of increasing outdoor play time on physical activity in Latino preschool children. AB - OBJECTIVE: A randomized controlled pilot study to test the hypothesis that increasing preschool children's outdoor free play time increases their daily physical activity levels. METHODS: Physical activity was assessed by accelerometers for four consecutive school days in thirty-two Latino children (3.6+/-0.5 years) attending a preschool for low-income families. After two days of baseline physical activity assessment, participants were randomly assigned to an intervention (RECESS; n =17) or control (CON; n =15) group. The RECESS group received two additional 30-minute periods of outdoor free play time per day for two days. The CON group followed their normal classroom schedule. Between group differences in physical activity variables were tested with a Wilcoxon rank-sum test. RESULTS: There were no statistically significant differences between groups in changes from baseline in average total daily (CON, 48.2+/-114.5; RECESS, 58.2+/-74.6) and during school day (CON, 64.6+/-181.9; RECESS, 59.7+/-79.1) counts per minute, or total daily (CON, 0.4+/-1.3; RECESS, 0.3+/-0.8) and during school day (CON, 0.6+/-2.1; RECESS, 0.5+/-0.8) percent of time spent in moderate to vigorous physical activity. CONCLUSIONS: Substantially increasing preschoolers' outdoor free play time did not increase their physical activity levels. PMID- 17852548 TI - Combined effect of body position, apparatus and distraction on children's resting metabolic rate. AB - OBJECTIVE: To verify the combined effect of body position, apparatus and distraction on children's resting metabolic rate (RMR). METHODS: Experiments were carried out on 14 children aged 8-12 (mean age = 10.1 years +/- 1.4). Each participant underwent two test sessions, one week apart under three different situations: a) using mouthpiece and nose-clip (MN) or facemask (FM); b) sitting (SEAT) or lying (LY); and c) TV viewing (TV) or no TV viewing. In the first session, following 20 min rest and watching TV, the protocol was: LY: 20 min stabilization; 10 min using MN and 10 min using FM. Body position was then changed to seated: 20 min stabilization; 10 min using FM; 10 min using MN. In the second session, FM and MN order was changed and participants did not watch TV. Data were analysed according to the eight combinations among the three studied parameters. RESULTS: Repeated measures ANOVA indicated statistically significant differences for VO2 (p =0.01) and RMR (p =0.02), with TVMNSEAT showing higher values than TVFMLY. Bland-Altman analysis showed a bias for VO2, VCO2, respiratory quotient (RQ) and RMR between TVFMLY and TVMNSEAT, respectively, of 17.8+/-14.5 (ml min), -8.8+/-14.5 (ml min), 0.03+/-0.05 and -115.2+/-101.9 (kcal/day). CONCLUSION: There were no differences in RMR measurements due to body position and apparatus when each variable was isolated. Analyses of distraction in three of four combinations indicated no difference between TV and no TV. Different parameter combinations can result in increased bias and variability, and thereby the reported differences among children's RMR measurement. PMID- 17852549 TI - Inflammatory markers are elevated in overweight Mexican-American children. AB - OBJECTIVE: The purpose of the present study was to determine the effect of body weight on blood lipid profile, insulin resistance and inflammatory biomarkers in Mexican-American children. METHODS: Children (13.3+/-0.1 year) were recruited from a local school and assigned to one of three groups as a volunteer sample: healthy weight (HW) (> or =10th and <85th BMI percentile; n=42), at risk of overweight (RO) (> or =85th and <95th; n =25) or overweight (OW) (> or =95th; n=42). Plasma concentrations of hsCRP, sCD14, sIL-6R, sTNF-alphaR1, sTNF-alphaR2, IL-6 and TNF-alpha were determined by ELISA. RESULTS: OW children had significantly greater plasma concentrations of hsCRP (P =0.003), sCD14 (P =0.013), sIL-6R (P =0.010), sTNF-alphaR1 (P<0.001), sTNF-alphaR2 (P=0.005), insulin (P=0.001), TC:HDL ratio (P<0.001) and triglycerides (P <0.001) than HW children. Also plasma concentrations of hsCRP, sIL-6R and sTNF-alphaR1 were significantly greater in OW compared with RO children. CONCLUSION: Overweight Mexican-American children had a higher concentration of inflammatory biomarkers than healthy weight children. To our knowledge, this is the first study to report that sCD14 is elevated in overweight compared with healthy weight Mexican American children. PMID- 17852550 TI - Factors associated with obesity in Indonesian adolescents. AB - OBJECTIVE. To investigate adolescent eating, activity, and behavioral patterns, and attitudes and their associations with obesity in selected communities in Indonesia. DESIGN. A cross-sectional questionnaire and physical measurement-based study in three communities of varying modernization levels in Indonesia (Yogyakarta, Kuta, and Jakarta). Subjects. 1758 middle school students (aged 12 15 years) recruited at six different schools: one public and one private school in each of the three target communities. MEASUREMENTS. The questionnaire collected data on demographic characteristics (age, gender, ethnicity, estimated household income); fast food eating habits (frequency, types of food/restaurant, general beliefs about fast foods); television, computer, and Play Station usage; physical activity (hrs/wk of participation in physical activity, transportation means for attending school); and eating habits (frequency of consuming selected foods and beverages). Student's height and weights were obtained, body mass index (BMI: weight [kg]/height [m(2)]) was calculated, and obesity was defined as >=95%, using the BMI-for-age cut-offs from the Centers for Disease Control and Prevention (CDC) charts. RESULTS. Chi-square analysis revealed associations between obesity and community setting, family income, use of a computer or Play Station, type of transportation to school, and beliefs about fast foods (P<0.01). According to the logistic regression analysis, adolescents from families with incomes over Rp 2 mil were three times as likely to be obese (95% CI 1.9, 4.9) and boys were 2.6 times more likely to be obese (95% CI 1.5, 4.5). CONCLUSION. Greater likelihood of obesity among Indonesian adolescents who spend greater amounts of time using a computer or Play Station suggests that such sedentary activities may be replacing physical activity, promoting an energy imbalance, and subsequently, an increased risk for obesity. PMID- 17852551 TI - Taste perception in massively obese and in non-obese adolescents. AB - OBJECTIVE: The purpose is to determine whether taste functions are different in massively obese adolescents as compared with non-obese adolescents, and to what extent metabolic disorders may interfere with taste perception, as suggested by the results of recent animal studies. RESEARCH METHOD AND PROCEDURES: We compared taste sensitivity and hedonic responses of 39 adolescents with severe early onset obesity (mean BMI: 39.5; min-max: 30.9-51.6) and 48 non-obese adolescents (mean BMI: 21.0; min-max: 16.5-27.9) of both sexes. We measured recognition thresholds for fructose, sucrose, citric acid and sodium chloride. Supra-threshold perceived intensity and hedonic responses were assessed for solutions of sucrose and sodium chloride. In obese subjects, the occurrence of the metabolic syndrome was assessed by measuring blood pressure and, in blood samples, fasting glycemia and insulinemia, the concentration of triglycerides and HDL cholesterol. HOMA modelling was used to assess insulin resistance. RESULTS: Massively obese adolescents present a higher sensitivity to sucrose and sodium chloride than non obese adolescents, with significantly lower recognition thresholds, and higher perceived intensities at supra-threshold levels for sucrose and salt. Hedonic responses are significantly lower for sodium chloride in the obese subjects. Among obese subjects, a significant positive correlation between taste responsiveness and the number of obesity-related metabolic disturbances is observed only in girls. CONCLUSION: Massively obese subjects have higher taste sensitivity than control subjects, especially for sucrose and salt. This can be explained, to some extent, by the influence of obesity-related metabolic disorders, which appears to be gender-specific. PMID- 17852552 TI - Calibration of an accelerometer during free-living activities in children. AB - OBJECTIVE: The aims of this study were to develop an equation to predict energy expenditure and to derive cut-points for moderate and vigorous physical activity intensity from the Actigraph accelerometer output in children aged 12 years. METHODS: The children performed a series of activities (lying, sitting, slow walking, fast walking, hopscotch and jogging) while wearing an Actigraph and a portable metabolic unit. The sample was divided into a developmental and a validation group. Random intercepts models were used to develop a prediction equation in the developmental group. The equation was assessed in the validation group by calculating limits of agreement (actual minus predicted energy expenditure). Thresholds for moderate and vigorous activity were derived by refitting the energy expenditure model with VO2 as the outcome. RESULTS: The developmental group comprised 163 children, while the validation group comprised 83 children. The equation, adjusted for age and gender, adequately predicted energy expenditure from accelerometer counts. Physical activity intensity cut points were derived from resting VO2. The lower threshold for moderate intensity (four METs), adjusted for age and gender, was 3581 counts per minute. The lower threshold for vigorous activity (six METs) was 6130 counts per minute. CONCLUSION: The prediction equation and the derived cut-points will help to better interpret the output of the Actigraph in children aged 12 years. The cut point for moderate to vigorous physical activity is higher than that reported previously. PMID- 17852553 TI - Low-intensity family therapy intervention is useful in a clinical setting to treat obese and extremely obese children. AB - AIMS: To study the influence of low-intensity solution-focused family therapy with obese and extremely obese pediatric subjects on body mass index (BMI) z scores and self-esteem. MATERIALS AND METHODS: Fifty-four obese children, aged 6 17 years, were referred to an outpatient obesity clinic. The families received solution-focused family therapy provided by a multidisciplinary team. Height and weight were recorded; BMI and BMI z-scores were derived. Self-esteem was assessed with a validated questionnaire, "I Think I Am." Parents completed "The Family Climate Scale" assessing family dynamics. RESULTS: Eighty-one percent of the children (n =44, mean age 11.9 years, mean BMI z-score 3.67, range 2.46-5.48) and their parents participated in the follow-up. Eleven children were treated for 6 12 months, and 33 for more than 12 months. On average, the families received 3.8 family therapy sessions. Intervention resulted in a mean decrease in BMI z-score of 0.12 (p =0.0001). Self-esteem on the global scale improved after intervention (p =0.002), and also on sub-scales, depicting physical characteristics (p <0.001), psychological well-being (p =0.026), and relations with others (p =0.046). The Family Climate Scale showed improvement in the sub-scales for Expressiveness (p = 0.002) and Chaos (p =0.002). CONCLUSIONS: Solution-focused family therapy provided by a multidisciplinary team to obese and extremely obese children may prove useful in the clinical setting, with a positive impact on obesity and self-esteem. PMID- 17852554 TI - LET dependence of the yield of single-, double-strand breaks and base lesions in fully hydrated plasmid DNA films by 4He(2+) ion irradiation. AB - PURPOSE: To characterize the complexity of DNA damage through determination of the yields of single (SSB) and double strand breaks (DSB), base lesions and clustered damage sites induced in fully hydrated plasmid DNA by direct radiation effects as a function of the ionizing density of the radiation using 4He(2+) ion irradiation with linear energy-transfer (LET) values in the range 19 to 148 keV/microm. MATERIALS AND METHODS: Hydrated plasmid DNA (pUC18) containing 34.5 water molecules/nucleotide was irradiated with He(2+) ions with LET values of 19, 63, 95, 121 and 148 keV/microm. From quantification of the conformational changes of the irradiated samples (closed circular, open or linear forms) analyzed by agarose gel electrophoresis, the yields of SSB and DSB were obtained. Base lesions were visualized as additional strand breaks by treatment with base excision repair enzymes (endonuclease III (Nth) and formamidpyrimidine DNA glycosylase (Fpg)). RESULTS: The yield of prompt SSB does not depend significantly on LET of the 4He(2+) ions, whereas the yield of prompt DSB increases with increasing LET. The yields of isolated base lesions, revealed by Nth and Fpg as additional SSB, decrease drastically with increasing LET. The sum of the yields of DSB and additional DSB revealed by Nth and Fpg increase with increasing LET of the 4He(2+) ions except at the highest LET investigated. CONCLUSION: The yields of clustered damage, revealed as DSB and non-DSB clustered damage sites, but not isolated lesions, namely SSB, increase with increasing ionization density of the 4He(2+) ions except at the highest LET investigated. PMID- 17852555 TI - Inactivation of chosen dehydrogenases by the products of water radiolysis and secondary albumin and haemoglobin radicals. AB - PURPOSE: Inactivation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), alcohol dehydrogenase (ADH) and lactate dehydrogenase (LDH) by products of water radiolysis and by secondary radicals localized on haemoglobin (Hb) and human albumin (HSA) was studied. MATERIALS AND METHODS: Aqueous solutions of ADH, GAPDH and LDH were irradiated under air and under nitrous oxide (N2O) in the absence and in the presence of Hb or HSA. In order to determine the effectiveness of inactivation of the enzymes by radicals localized on Hb and HSA, the inactivation efficiency determined experimentally was compared with that calculated under assumption that only hydroxyl radicals are responsible for the enzyme inactivation. RESULTS: In the absence of other proteins, under air, GAPDH showed the highest radiation sensitivity, followed by ADH and LDH. The sequence was reverse under anaerobic atmosphere. Oxygen increased considerably the inactivation of GAPDH and ADH. Secondary albumin and haemoglobin radicals brought about considerable inactivation of GAPGH and ADH. Albumin radicals (HSA) generated under N2O inactivated GAPDH and ADH more effectively than haemoglobin radicals (Hb). Under air, however, inactivation of GAPDH and ADH by haemoglobin peroxyl radicals was higher than by albumin peroxyl radicals. LDH was resistant to inactivation by haemoglobin and albumin radicals, and peroxides of these proteins. CONCLUSIONS: In the light of these results and literature data, the observed differences in the effectiveness of inactivation of the dehydrogenases studied by secondary protein radicals depend on the amino acid residues present at the active site and in its close neighborhood and on the number of amino acid residues available on the protein surface. PMID- 17852556 TI - Extremely low frequency (ELF) magnetic fields enhance chemically induced formation of apurinic/apyrimidinic (AP) sites in A172 cells. AB - PURPOSE: To detect the effects of extremely low frequency (ELF) magnetic fields, the number of apurinic/apyrimidinic (AP) sites in human glioma A172 cells was measured following exposure to ELF magnetic fields. MATERIALS AND METHODS: The cells were exposed to an ELF magnetic field alone, to genotoxic agents (methyl methane sulfonate (MMS) and hydrogen peroxide (H2O2)) alone, or to an ELF magnetic field with the genotoxic agents. After exposure, DNA was extracted, and the number of AP sites was measured. RESULTS: There was no difference in the number of AP sites between cells exposed to an ELF magnetic field and sham controls. With MMS or H2O2 alone, the number of AP sites increased with longer treatment times. Exposure to an ELF magnetic field in combination with the genotoxic agents increased AP-site levels compared with the genotoxic agents alone. CONCLUSIONS: Our results suggest that the number of AP sites induced by MMS or H2O2 is enhanced by exposure to ELF magnetic fields at 5 millitesla (mT). This may occur because such exposure can enhance the activity or lengthen the lifetime of radical pairs. PMID- 17852557 TI - Hypoxia inducible factor (HIf1alpha and HIF2alpha) and carbonic anhydrase 9 (CA9) expression and response of head-neck cancer to hypofractionated and accelerated radiotherapy. AB - PURPOSE: Tumor hypoxia and low intrinsic radiosensitivity may counteract the efficacy of standard radiotherapy for locally advanced head and neck cancer (HNC). We investigated the involvement of hypoxia-regulated proteins (Hypoxia inducible factors HIF1alpha, HIF2alpha and carbonic anhydrase CA9) in HNC resistance to accelerated and hypofractionated radiotherapy. MATERIALS AND METHODS: Thirty-nine patients with locally advanced HNC received 15 daily fractions of 3.4 Gy amounting to a total tumor dose of 51 Gy (equivalent to 63 Gy in four weeks--one week split); this was combined with platinum chemotherapy and amifostine cytoprotection administered subcutaneously. Immunohistochemical analysis of hypoxia-regulated proteins, namely HIF1alpha, HIF2alpha and CA9, was performed in formalin-fixed paraffin-embedded tissues obtained prior to radio chemotherapy. RESULTS: HIF1alpha and HIF2alpha were expressed in the nuclei and cytoplasm of cancer cells, while CA9 had a membrane reactivity. A high expression of HIF1alpha, HIF2alpha and CA9 was noted in 21/39 (53.8%), 20/39 (51.3%) and 23/39 (58.9%) cases, respectively. Complete response was obtained in 85.2% of patients and HIF1alpha was marginally related with persistent disease after RT (p = 0.05). HIF1alpha was significantly associated with poor local relapse free survival (LRFS) (p = 0.006) and overall survival (p = 0.008), whilst HIF2alpha was not. A significant association of CA9 expression with poor LRFS was noted (p = 0.01). CONCLUSION: In accord with previously reported studies, high levels of the hypoxia regulated proteins HIF1alpha and CA9 in HNC predict resistance to platinum based radio-chemotherapy. Whether HIF2alpha expressing tumors are more sensitive to larger radiotherapy fractions, compared to standard radiotherapy fractionation, is an issue that deserves further investigation. PMID- 17852558 TI - Long-lasting alterations of the immune system by ionizing radiation exposure: implications for disease development among atomic bomb survivors. AB - PURPOSE: The immune systems of the atomic-bomb (A-bomb) survivors were damaged proportionately to irradiation levels at the time of the bombing over 60 years ago. Although the survivor's immune system repaired and regenerated as the hematopoietic system has recovered, significant residual injury persists, as manifested by abnormalities in lymphoid cell composition and function. This review summarizes the long-lasting alterations in immunological functions associated with atomic-bomb irradiation, and discusses the likelihood that damaging effects of radiation on the immune system may be involved partly in disease development so frequently observed in A-bomb survivors. CONCLUSIONS: Significant immunological alterations noted include: (i) attrition of T-cell functions, as reductions in mitogen-dependent proliferation and interleukin-2 (IL 2) production; (ii) decrease in helper T-cell populations; and (iii) increase in blood inflammatory cytokine levels. These findings suggest that A-bomb radiation exposure perturbed one or more of the primary processes responsible for T-cell homeostasis and the balance between cell renewal and survival and cell death among naive and memory T cells. Such perturbed T-cell homeostasis may result in acceleration of immunological aging. Persistent inflammation, linked in some way to the perturbation of T-cell homeostasis, is key in addressing whether such noted immunological changes observed in A-bomb survivors are in fact associated with disease development. PMID- 17852559 TI - Extracellular matrix regulation of drug resistance in small-cell lung cancer. AB - PURPOSE: Lung cancer is the leading cause of cancer deaths in the developed world. Small cell lung cancer (SCLC) has the worst prognosis due to the emergence of resistance to chemotherapy. This article will review recent work that has defined mechanisms of chemo-resistance focusing on the role of integrins. RESULTS: SCLC is surrounded by an extensive stroma of extracellular matrix (ECM) and high levels of expression correlate with poor prognosis. ECM protects SCLC cells against chemotherapy-induced cell death by activating beta1 integrins leading to activation of phosphoinositide-3-OH kinase (PI3-kinase), which prevents etoposide-induced caspase-3 activation and subsequent apoptosis. Engagement of ECM prevents etoposide and radiation induced G2/M cell cycle arrest in SCLC cells by blocking the up-regulation of p21Cip1/WAF1 and p27Kip1 and the down-regulation of cyclins E, A and B. These effects are abrogated by pharmacological and genetic inhibition of PI3-kinase signalling. CONCLUSIONS: Thus, ECM via beta1 integrin-mediated PI3-kinase activation allows SCLC cells to survive treatment induced cell cycle arrest and apoptosis with persistent DNA damage, providing a model to account for the emergence of acquired drug resistance. Novel therapeutic strategies may therefore be directed at inhibiting integrin-mediated cell survival signals improving response rates and cure in this devastating cancer. PMID- 17852560 TI - Adoptive transfer of cytotoxic T-cells for treatment of residual disease after irradiation. AB - PURPOSE: To evaluate whether immunotherapy based on adoptively transferred cytotoxic T-cells (CTL) can improve the antitumour efficacy of irradiation. MATERIAL AND METHODS: The experiments were performed using the human squamous cell carcinoma line UT-SCC-15, which expresses human leukocyte antigen (HLA)-A2. The UT-SCC-15 cell-mediated activation of JB4 CTL in terms of interferon (IFN) gamma secretion and cytotoxic potential was determined by enzyme-linked immunosorbent assay and chromium release assay, the perforin content of JB4 cells by flow cytometry. In vivo, tumours were irradiated with 14 Gy. Subsequently, JB4 CTL were injected intra- and peritumourally. Volume doubling times were calculated as a marker of tumour growth delay. RESULTS: UT-SCC-15 tumour cells were well recognized by JB4 CTL in vitro, as indicated by profound IFN-gamma secretion and tumour cell lysis. This response was completely abrogated in the presence of an anti-HLA-A2 antibody. In vivo, adoptive transfer of JB4 CTL after irradiation did not delay tumour growth in comparison to irradiation alone. As a possible underlying mechanism, a loss of perforin content and cytolytic function of the CTL in the absence of interleukin (IL)- 2 or IL-15 was found in vitro. CONCLUSION: HLA-A2-alloreactive JB4 cells efficiently recognize and destroy UT SCC-15 tumour cells in vitro. However, the intratumoural application of JB4 cells after irradiation does not enhance the in vivo effect of radiotherapy alone, which might be caused by the reduced cytotoxic potential of JB4 cells in the absence of IL-2 or IL-15. Thus, co-administration of these cytokines might improve the efficacy of combined irradiation and CTL treatment. PMID- 17852561 TI - Sensors of ionizing radiation effects on the immunological microenvironment of cancer. AB - PURPOSE: When cancer develops in an immunocompetent host it represents the result of a successful deception of the immune system as to the nature of the danger and the type of response needed to reject the neoplastic tissue. We will briefly review some of the recently emerged evidence that irradiation of the tumor and its microenvironment can induce essential molecular signals required for an effective response of the immune system to the tumor. CONCLUSIONS: The subversion of a highly organized tissue architecture is a hallmark of cancer, and results in uneven distribution of oxygen and nutrients, interstitial pressure gradients and areas of patchy necrosis and inflammation. In this microenvironment, cancer cells that carry mutations favoring survival rather than cell death in response to stress find a selection advantage. Importantly, the signals derived from the disruption of orderly physiology within tissues are also what the immune system has evolved to respond to. The type of response is tuned to be adequate to the cause of the disruption. An infectious organism will carry or elicit from the involved tissue a number of 'danger signals' leading to development of cell mediated and humoral responses to both eliminating the invader and preventing future infections. In contrast, a simple wound will call for a repair response. The sensors of the type of damage are complex molecular interactions between the damaged organ and cells of the innate and adaptive immune system. Progress in the identification of these interactions elucidates which pathways are specifically altered in cancer. It also provides a novel understanding of the radiation induced effects on tumor immunogenicity. We propose that specific radiation induced effects could be successfully exploited to improve the effectiveness of immunotherapy. PMID- 17852562 TI - Integrins: signaling, disease, and therapy. AB - BACKGROUND: Integrins are a family of transmembrane receptors that mediate cell cell and cell-matrix adhesion. They are involved in stable cell adhesion and migration of cells. In addition, integrin-mediated interactions modulate the response to most, if not all growth factors, cytokines, and other soluble factors. PURPOSE: In this review, we briefly explain how integrins can affect the multitude of signal transduction cascades in control of survival, proliferation, and differentiation. Subsequently, we primarily focus on targeting integrins alpha5beta1 and alphanubeta3 in disease and we discuss how antagonists of these integrins, including disintegrins, RGD peptides, small molecules, and function blocking antibodies, may be of therapeutical value either alone or, especially in the treatment of cancer, in combination with existing therapeutical strategies. PMID- 17852563 TI - Effect of GSM-900 and -1800 signals on the skin of hairless rats. III: Expression of heat shock proteins. AB - PURPOSE: We previously reported the inability of Global System for Mobile communication (GSM) signals at 900 (GSM-900) and 1800 (GSM-1800) MegaHertz (MHz) to induce morphological and physiological changes in epidermis of Hairless rats. The present work aimed at investigating heat shock proteins (HSP) expression--as a cellular stress marker--in the skin of Hairless rats exposed to GSM-900 and 1800 signals. MATERIALS AND METHODS: We studied the expression of the Heat-shock cognate (Hsc) 70, and the inducible forms of the Heat-shock proteins (Hsp) 25 and 70. Rat skin was locally exposed using loop antenna and restrain rockets to test several Specific Absorption Rates (SAR) and exposure durations: (i) single exposure: 2 hours at 0 and 5 W/kg; (ii) repeated exposure: 2 hours per day, 5 days per week, for 12 weeks, at 0, 2.5, and 5 W/kg. HSP expression was detected on skin slices using immunolabeling in the epidermal area. RESULTS: Our data indicated that neither single nor repeated exposures altered HSP expression in rat skin, irrespective of the GSM signal or SAR considered. CONCLUSIONS: Under our experimental conditions (local SAR < 5 W/kg), there was no evidence that GSM signals alter HSP expression in rat skin. PMID- 17852564 TI - Comparative RNomics and modomics in Mollicutes: prediction of gene function and evolutionary implications. AB - Stable RNAs are central to protein synthesis. Ribosomal RNAs make the core of the ribosome and provide the scaffold for accurate translation of mRNAs by a set of tRNA molecules each carrying an activated amino acid. To fulfill these important cellular functions, both rRNA and tRNA molecules require more than the four canonical bases and have recruited enzymes that introduce numerous modifications on nucleosides. Mollicutes are parasitic unicellular bacteria that originated from gram-positive bacteria by considerably reducing their genome, reaching a minimal size of 480 kb in Mycoplasma genitalium. By analyzing the complete set of tRNA isoacceptors (tRNomics) and predicting the tRNA/rRNA modification enzymes (Modomics) among all sequenced Mollicutes (15 in all), our goal is to predict the minimal set of RNA modifications needed to sustain accurate translation of the cell's genetic information. Building on the known phylogenetic relationship of the 15 Mollicutes analyzed, we demonstrate that the solutions to reducing the RNA component of the translation apparatus vary from one Mollicute to the other and often rely on co-evolution of specific tRNA isoacceptors and RNA modification enzymes. This analysis also reveals that only a few modification enzymes acting on nucleotides of the anticodon loop in tRNA (the wobble position 34 as well as in position 37, 3'-adjacent to anticodon) and of the peptidyltransferase center of 23S rRNA appear to be absolutely essential and resistant to gene loss during the evolutionary process of genome reduction. PMID- 17852565 TI - What are prostasomes?. PMID- 17852566 TI - Identification and biochemical properties of Dps (starvation-induced DNA binding protein) from cyanobacterium Anabaena sp. PCC 7120. AB - DNA-binding Proteins from Starved cells (Dps) are anti-stress iron proteins preserving bacteria from oxidative damage. Based on sequence alignment, a 564-bp open reading frame (all1173) encoding product in Anabaena sp. PCC 7120 shared high similarity with Dps family proteins. RT-PCR showed all1173 is active at transcriptional level in Anabaena sp. PCC 7120 cells. We accordingly cloned the all1173 into prokaryotic expression system, purified the corresponding recombinant protein (Dps1173) and characterized its properties in vitro. According to CD spectrum and non-denaturing electrophoresis assays, recombinant Dps1173 was alpha helix riched, and was likely to form dodecametric oligomer under native conditions. Fluorescence titration experiment revealed two major iron binding sites within Dps1173 monomer, indicating its potential ferroxidase activity. Although phenomena of direct DNA binding was not observed in Electrophoretic mobility shift assay, Dps1173 could also protect DNA from H2O2 stress for its iron scavenging capacity. This is the first description of Dps from heterocystous cyanobacterium Anabaena sp. PCC 7120. PMID- 17852567 TI - How I became a biochemist: an honorary one! PMID- 17852568 TI - Functional connections and pathways of coenzyme Q10-inducible genes: an in-silico study. AB - Coenzyme Q10 (CoQ10, ubiquinone) is an essential cofactor in the electron transport chain, serves as a potent antioxidant in mitochondria and lipid membranes, and is often used as a dietary supplement for a number of diseases including cardiovascular diseases. Recently, we obtained evidence that CoQ10 (Kaneka Q10) affects the expression of hundreds of human genes. To decipher the functional and regulatory connections of these genes, a literature search combined with transcription factor binding site analysis was performed using Genomatix BiblioSphere and MatInspector. This in-silico analysis revealed 17 CoQ10-inducible genes which are functionally connected by signalling pathways of G-protein coupled receptors, JAK/STAT, integrin, and beta-arrestin. Promoter analysis of these CoQ10-inducible genes showed one group of NF B-regulated genes, namely IL5, thrombin, vitronectin receptor and C-reactive protein (CRP). Furthermore, a common promoter framework containing binding sites of the transcription factor families EVI1, HOXF, HOXC, and CLOX was identified in the promoters of IL5, CRP, and vitronectin receptor. The identified CoQ10-inducible genes and pathways play an important role in inflammatory response. Since these effects are based on an in-vitro study, the effect of CoQ10 on vascular health in vivo needs to be addressed in further animal and/or human intervention studies. PMID- 17852569 TI - Implication of PKC in the seasonal variation of the immune response of the hemocytes of Mytilus galloprovincialis Lmk. and its role in interleukin-2-induced nitric oxide synthesis. AB - The hemocytes are the cells responsible for the immune response in marine mollusks. The role of NO in processes related to the activation of the hemocytes has turned out evident over the late years. In the case of the mussel Mytilus galloprovincialis Lmk., hemocyte NO basal production varies throughout the year, showing a maximum in summer and a minimum in winter. IL-2 reverts the low winter NO basal production through a process mediated by cAMP-dependent protein kinase and by an apparent side effect of protein kinase C. The seasonal variation of NO production in the presence of the PKC inhibitor bisindolylmaleimide (BSM) allows suggesting a model in which PKC would modulate the activity of the enzymes responsible for nitric oxide production. PMID- 17852571 TI - Do nonribosomal peptide synthetases occur in higher eukaryotes? AB - Is There An Answer? is intended to serve as a forum in which readers to IUBMB Life may pose questions of the type that intrigue biochemists but for which there may be no obvious answer or one may be available but not widely known or easily accessible. Readers are invited to e-mail ascenzi@uniroma3.it if they have questions to contribute or if they can provide answers to questions that are provided here from time to time. In the latter case, instructions will be sent to interested readers. Answers should be, whenever possible, evidence-based and provide relevant references. Paolo Ascenzi PMID- 17852579 TI - Comparison of nondominant- and dominant-hand performances on the copy portion of the Rey Complex Figure Test (RCFT). AB - Road accidents and falls often result in injury to the dominant hand; however, few studies have evaluated whether the use of the nondominant hand confounds pen and paper assessments. This study used a counterbalanced within-subjects design to assess the copy accuracy on the Rey Complex Figure Test (RCFT) of 154 undergraduates using both their right and left hands. Handedness was determined using Briggs and Nebes's (1975) revision of Annett's Handedness Questionnaire. Two independent scorers used objective scoring criteria (Meyers & Meyers, 1995) with high interscorer reliability. Performance differences were statistically but not clinically significant. Nondominant- and dominant-hand performances did not differ from normative data: A total of 78.9% scored above the impairment cutoff score using the nondominant hand compared to 83.7% using their dominant hand. In the event an individual's dominant hand is compromised, performance using the nondominant hand on the RCFT could produce scores within the normative range and would not falsely suggest neuropsychological impairment. PMID- 17852584 TI - Spatial and temporal memories are affected by sleep fragmentation in obstructive sleep apnea syndrome. AB - This study evaluated episodic memory, with an emphasis on the recollection of spatial and temporal contexts, in 28 patients suffering from obstructive sleep apnea syndrome and 29 healthy controls. Recollection was assessed by means of the R/K paradigm and the process-dissociation procedure. Attentional abilities were also evaluated. A polysomnographic assessment, including nocturnal oxygen saturation and daytime sleepiness, was conducted. Recollection was strongly disturbed in patients, the number of microarousals being the best predictor of the memory deficit. Attention was only slightly disturbed. Results suggest a link between episodic memory deficit and those areas of the brain that are particularly sensitive to sleep fragmentation, in particular the hippocampus. PMID- 17852582 TI - Predictive validity of demographically adjusted normative standards for the HIV Dementia Scale. AB - The aim of the current study was to develop and validate demographically adjusted normative standards for the HIV Dementia Scale (HDS). Given the association between demographic variables and the HDS summary score, demographically adjusted normative standards may enhance the classification accuracy of the HDS. Demographically adjusted normative standards were derived from a sample of 182 seronegative healthy participants and were subsequently applied to a sample of 135 HIV-1 seropositive individuals with multidisciplinary case conference diagnoses of HIV-1-associated neurocognitive disorders (e.g., HIV-1-associated dementia and minor-cognitive/motor disorder) in proportions consistent with published epidemiologic reports. In the normative sample, age and education (and their interaction) emerged as the only demographic factors significantly associated with the HDS. In comparison to the traditional HDS cut score (raw score total 75% reduction in the PASI score, while in the hydroxycarbamide group only two (13.33%) patients showed similar results, signifying that methotrexate leads to a faster clearance of the disease. The methotrexate-related side effects, however, were also higher. CONCLUSIONS: Weekly doses of hydroxycarbamide can be used as an alternative to methotrexate in patients who either experience intolerable methotrexate side effects or have achieved its recommended cumulative dose. PMID- 17852636 TI - Methotrexate-betamethasone weekly oral pulse in psoriasis. AB - OBJECTIVES: Methotrexate in psoriasis helps to clear the lesions fast but remission is short. To produce long-term remission, methotrexate has been combined with betamethasone. METHODS: A total of 40 patients with psoriasis (plaque type: 36, erythrodermic: four) were included in an open randomized study. Twenty-eight patients received weekly 15 mg methotrexate and 3 mg betamethasone orally and 12 patients received weekly 15 mg methotrexate orally alone until the Psoriasis Area Severity Index (PASI) scores were reduced to 95-100% of the baseline scores. Follow-up was carried out until relapse of the lesions. RESULTS: Methotrexate combined with betamethasone orally weekly cleared the lesions in 27.13+/-2.39 (24.74-29.52) days with a remission period of 91.78+/-14.19 (77.59 105.97) days, whereas methotrexate alone took 33.09+/-5.61 (27.48-38.70) days to clear the lesions with a remission period of 20.30+/-2.50 (17.80-22.80) days. CONCLUSIONS: Methotrexate combined with betamethasone cleared the lesions faster and with a longer remission period compared with methotrexate alone. PMID- 17852637 TI - Thalidomide: an experience in therapeutic outcome and adverse reactions. AB - BACKGROUND: The US FDA-approved thalidomide for the treatment of chronic recurrent/severe erythema nodosum leprosum. Thalidomide is also useful in many other inflammatory dermatological conditions where patients have exhausted other treatment options. METHODS: The beneficial and adverse clinical effects of thalidomide were studied in 25 patients suffering from different inflammatory dermatological conditions that were poorly controlled with conventional therapies. RESULTS: Thalidomide was found to be effective in various inflammatory dermatological diseases other than chronic recurrent erythema nodosum leprosum such as Behcet's disease, disseminated and hypertrophic discoid lupus erythematosus, erosive lichen planus, discoid lupus erythematosus-lichen planus overlap, recurrent aphthous stomatitis and prurigo nodularis. Deep vein thrombosis due to thalidomide occurred in 20% of these patients and appears to be a significant side effect. CONCLUSION: Thalidomide appears promising in a number of inflammatory dermatological conditions and will probably find new usages in future. The treating physicians need to be wary of the thrombo-embolic complications due to thalidomide especially when glucocorticoids or other chemotherapeutic agents such as doxorubicin, gemcitabine, 5-fluorouracil or dexamethasone-cyclophosphamide pulse therapy are being used concomitantly, and in patients of metastatic renal carcinoma, myelodysplastic syndrome or multiple myeloma receiving thalidomide/chemotherapy. Antiphospholipid or anticardiolipin antibodies appear to be other possible risk factors for this complication. PMID- 17852638 TI - The imperatives of leprosy treatment in the pre- and post-global leprosy elimination era: appraisal of changing the scenario to current status. AB - Leprosy was supposed to be eliminated by WHO at the global level by the end of the year 2000; however, it still remains a significant public health problem at a national level in six countries, where India alone accounts for 64% of prevalence and 78% of new case detection, worldwide. The global registered prevalence of leprosy at the beginning of 2006 was 219,826 cases. The number of new cases reported during 2005 was 296,499. The clinical diagnosis of leprosy continues to be based on patients having one or more of the three cardinal signs: hypopigmented or reddish anesthetic skin lesion(s); involvement of the peripheral nerves, as demonstrated by definite thickening with loss of sensation in the area of distribution; and a positive skin smear for acid-fast bacilli. Multidrug therapy (MDT) for leprosy has proved to be highly effective, with low relapse rates resulting in a dramatic decrease in the global prevalence rate to less than one case per 10 000 by the end of the year 2000. It was thought to be worthwhile to review the progress made in the treatment of this neglected tropical disease from the time diaminodiphenylsulfone (dapsone) monotherapy was introduced in its management, to the rapidly changing situation following the advent of WHO recommended MDT and subsequently to short-course newer drug regimens with the prime objective to eliminate/eradicate leprosy from the world. Several permutations and combinations of drugs were utilized, the outline of which are succinctly depicted in the following account. Furthermore, a synopsis of the role of immunoprophylaxis therapy has briefly been reviewed to arrive at the possible current status. It is expected that this article is not only essential at this point in time but is also likely to make clear the intricacies surrounding its management. PMID- 17852639 TI - The use of oral cyclophosphamide with dexamethasone pulse therapy in the treatment of pemphigus vulgaris. AB - BACKGROUND: Pemphigus vulgaris (PV) is a severe acquired autoimmune disease. During the past 15 years we used dexamethasone pulse therapy (DP) and oral cyclophosphamide for treatment of our patients with PV. OBJECTIVES: To evaluate the efficacy and side effects of this treatment. METHOD: The study was a retrospective study. Medical records of 50 known cases of PV, who were treated with dexamethasone pulse therapy and oral cyclophosphamide were evaluated and the patients were re-examined and questioned about their current situations. RESULTS: Thirty-five females and 15 males were treated, out of which 38 finished the study. At the end of study, 21 patients were in remission, 10 patients were in the healing stage, five patients were partially healed and two patients died. The side effects of this method, especially the adverse effects of cyclophosphamide, were less than previously reported. CONCLUSION: Dexamethasone pulse therapy and oral cyclophosphamide is an effective regimen with few side effects in the treatment of mild to moderate PV. PMID- 17852640 TI - Coal tar in dermatology. AB - Coal tar is one of the oldest treatments for psoriasis and eczema. It has anti inflammatory, antibacterial, antipruritic and antimitotic effects. The short-term side effects are folliculitis, irritation and contact allergy. Coal tar contains carcinogens. The carcinogenicity of coal tar has been shown in animal studies and studies in occupational settings. There is no clear evidence of an increased risk of skin tumors or internal tumors. Until now, most studies have been fairly small and they did not investigate the risk of coal tar alone, but the risk of coal tar combined with other therapies. New, well-designed, epidemiological studies are necessary to assess the risk of skin tumors and other malignancies after dermatological use of coal tar. PMID- 17852641 TI - Washability and fabric-staining properties of a novel phospholipid-structured coal tar formulation. AB - BACKGROUND: Coal tar is one of the most preferred and frequently used medicinal agents in various dermatological diseases. However, the coal tar formulations available for clinical use suffer from the limitation of staining clothes and skin, eventually leading to a high degree of patient non-compliance. OBJECTIVE: To test the staining property of a lecithinized formulation vis-a-vis a conventional formulation of coal tar employing different types of fabric. METHODS: Six fabrics with different blends of cotton and polyester were employed to test the staining and washability of two coal tar formulations following application for 24 hours and 48 hours. RESULTS: The study revealed the distinct superiority of the lecithinized coal tar formulation vis-a-vis the conventional marketed formulation due to its markedly reduced staining and easier washability. A significant reduction in the staining of fabrics containing polyester was observed with the lecithinized formulation, with the stain becoming progressively worse as the proportion of polyester in the fabric increased. The stains washed off completely with detergent in the case of the lecithinized coal tar formulation, whereas stains from the conventional coal tar formulation remained intact. CONCLUSION: The developed lecithinized formulation, owing to its superior non-staining and washability characteristics, would potentially increase the acceptability of coal tar amongst patients. PMID- 17852642 TI - Efficacy and problems associated with using a wet-wrap garment for children with severe atopic dermatitis. AB - Use of a wet wrap for short-term relief of itch in children with severe atopic dermatitis has been advocated but objective determination of its efficacy has been difficult and many issues associated with its use are yet to be defined. We tested a new garment for the wet-wrap procedure in six patients with atopic dermatitis and objectively determined whether a 3-day usage could indeed relieve the distressing symptom of itch using a wrist motion monitor. The garments were effective in the short-term improvement of itching, severity of atopic dermatitis and quality of life in these children. Many issues associated with its use were identified. Clear instructions and individualized regimes (such as the choice of emollient, bathing ointment and topical corticosteroid) are essential for optimal outcome. PMID- 17852643 TI - Prolonged treatment with rituximab in patients with refractory pemphigus vulgaris. AB - OBJECTIVES: Recent reports have documented swift responses in refractory pemphigus vulgaris to rituximab, a monoclonal anti-CD20 antibody. Nevertheless, no standard protocol has yet been established for the administration of rituximab in patients with pemphigus vulgaris. We report the results of prolonged treatment with rituximab therapy in two patients with refractory pemphigus vulgaris. METHODS: A 22- and a 27-year-old man were diagnosed with pemphigus vulgaris according to clinical, histopathological and immunofluorescence criteria. They failed to respond after several years of steroid and immunosuppressive treatment and experienced adverse effects. Rituximab was administered intravenously at a dose of 375 mg/m2 once weekly for 4 weeks. RESULTS: Single infusions of rituximab 375 mg/m2 were repeated at 2-monthly intervals four times because of a delayed response. The treatment was well tolerated, no side effects were observed and the previous corticosteroid therapy could be progressively withdrawn. CONCLUSIONS: The good response of our patients suggests that rituximab may be a valuable treatment option for refractory pemphigus vulgaris. It is important that clinicians are aware that the response to rituximab in pemphigus may be delayed, and that prolonged treatment may have a good outcome. PMID- 17852646 TI - New less invasive approach for determination of the sodium concentration in human venous blood. AB - This paper presents a new, less invasive method for determination of sodium concentration in human venous blood. This new method is based on estimation of the blood sodium by measuring the sodium concentration in urine and potassium in blood. It allows the measurement of sodium concentration with an accuracy satisfying medical requirements. The main features of this method are that it is less invasive method in comparison with conventional methods for sodium concentration measurement in human blood, and it reduces the cost related to sodium analysis and measurement. Experimental verification of this method with results is also included. PMID- 17852647 TI - Finite element modeling of the thoracic aorta: including aortic root motion to evaluate the risk of aortic dissection. AB - OBJECTIVE: We propose that the aortic root motion plays an important role in aortic dissection. METHODS AND RESULTS: A finite element model of the aortic root, arch and branches of the arch was built to assess the influence of aortic root displacement and pressure on the aortic wall stress. The largest stress increase due to aortic root displacement was found at approximately 2 cm above the top of the aortic valve. There, the longitudinal stress increased by 50% to 0.32 MPa when 8.9 mm axial displacement was applied in addition to 120 mmHg luminal pressure. A similar result was observed when the pressure load was increased to 180 mmHg without axial displacement. CONCLUSIONS: Both aortic root displacement and hypertension significantly increase the longitudinal stress in the ascending aorta, which could play a decisive role in the development of various aortic pathologies, including aortic dissection. PMID- 17852648 TI - Advanced integrated technique in breast cancer thermography. AB - Thermography is a passive and non-contact imaging technique used extensively in the medical arena, but in relation to breast care, it has not been accepted as being on a par with mammography. This paper proposes the analysis of thermograms with the use of artificial neural networks (ANN) and bio-statistical methods, including regression and receiver operating characteristics (ROC). It is desired that through these approaches, highly accurate diagnosis using thermography techniques can be achieved. The suggested method is a multi-pronged approach comprising of linear regression, radial basis function network (RBFN) and ROC analysis. It is a novel, integrative and powerful technique that can be used to analyse large amounts of complicated measured data such as temperature values extracted from abnormal and healthy breast thermograms. The use of regression allows the correlation between the variables and the actual health status of the subject, which is decided by other traditional means such as the gold standard of mammography for breast cancer detection. This is important as it helps to select the appropriate variables to be used as inputs for building the neural network. RBFN is next trained to produce the desired outcome that is either positive or negative. When this is done, the RBFN possess the ability to predict the outcome when there are new input variables. The advantages of using RBFN include fast training of superior classification and decision-making abilities as compared to other networks such as backpropagation. Lastly, ROC is applied to evaluate the sensitivity, specificity and accuracy of the outcome for the RBFN test files. The proposed technique has an accuracy rate of 80.95%, with 100% sensitivity and 70.6% specificity in identifying breast cancer. The results are promising as compared to clinical examination by experienced radiologists, which has an accuracy rate of approximately 60-70%. To sum up, technological advances in the field of infrared thermography over the last 20 years warrant a re-evaluation of the use of high-resolution digital thermographic camera systems in the diagnosis and management of breast cancer. Thermography seeks to identify the presence of a tumour by the elevated temperature associated with increase blood flow and cellular activity. Of particular interest would be investigation in younger women and men, for whom mammography is either unsuitable or of limited effectiveness. The paper evaluated the high-definition digital infrared thermographic technology and knowledge base; and supports the development of future diagnostic and therapeutic services in breast cancer imaging. Through the use of integrative ANN and bio-statistical methods, advances are made in thermography application with regard to achieving a higher level of consistency. For breast cancer care, it has become possible to use thermography as a powerful adjunct and biomarker tool, together with mammography for diagnosis purposes. PMID- 17852649 TI - Three-part passive constitutive laws for the aorta in simple elongation. AB - A variety of uniaxial constitutive laws have been proposed for the characterization of the aorta's nonlinear passive response, but a detailed comparison of them appears to be lacking. In this study, a systematic presentation of all available phenomenological formulations is undertaken and explicit formulae of constitutive laws are provided for simple elongation tests performed on healthy aortic strips. Common to all derived laws is the use of three analytical functions to approximate the low, physiologic, and high-stress parts of the aortic response, and the very close and essentially equally accurate fits that they give to the experimental data over the full range of stresses. Another feature of the three-part laws is their compatibility with the biphasic nature of the aortic tissue under passive conditions, allowing direct microstructural interpretation of their parameters. Importantly, although it is found that the aorta displays strain softening, i.e. its passive response is dependent on the highest previously experienced stress, the three-part character of the laws seems to be unaffected by the preconditioning procedure. PMID- 17852650 TI - Difference in pulse transit time between populations: a comparison between Caucasian and Chinese children in Australia. AB - Pulse wave velocity (PWV) has shown to be a clinically important physiologic measure in the assessment of increased arterial stiffness that is linked to systolic hypertension. Pulse transit time (PTT), which is based on the principle of PWV, has become popular in childhood cardiovascular studies. A previous study has indicated PWV obtained from a Chinese population tends to be higher than that from their Caucasian counterpart of similar age but of different localities. In this study, 67 healthy children (55 Caucasian and 12 Chinese) were recruited to investigate the possible PTT difference between these two ethnic groups in the same region. However, the hypothesized PWV difference (p < 0.05) between them is not observed here in the corresponding PTT measurements (time-related PWV equivalent). Hence, preliminary results suggest that locality or inclusion of pre ejection period, which forms the major component of the PTT measurement, may contribute to this discrepancy. PMID- 17852651 TI - Reverse engineering techniques for cranioplasty: a case study. AB - This paper presents rapid prototyping and reverse engineering techniques applied to create an implant for the surgical reconstruction of a large cranial defect. A series of computed tomography (CT) images was obtained and purpose built software was used to extract the cranial geometry in a point cloud. The point cloud produced was used for: (a) the creation of a stereolithographic (STL) physical model for direct assessment of the cranial defect; and (b) the creation of a 3D mould model for the fabrication of the patient-specific implant. PMID- 17852652 TI - Preparation of polyurethane nanocapsules by miniemulsion polyaddition. AB - The encapsulation of organic liquids in polyurethane nanocapsules by interfacial miniemulsion polycondensation of isophorone diisocyanate and propanetriol has been performed. The influence of type and amount of encapsulated organic liquid has been studied and it was found that the encapsulation efficiency is dependent on the water solubility of the organic liquids, their interfacial tension against water and their compatibility with polyurethane. It was also shown how different types of surfactants and variations in pH and ionic strength of the continuous phase affected the stability during polymerization and the diameter of the miniemulsion droplets and the resulting nanocapsules. The long-chained anionic surfactant Disponil FES77 can be utilized over a larger pH range than SDS due to the contribution of steric stabilization. Relatively narrow size distributions were obtained. PMID- 17852653 TI - Remembering the pain: accuracy of pain recall in endometriosis. AB - Endometriosis diagnosis and treatment planning are guided primarily by retrospective pain recall, despite the facts that (1) there is only a tenuous relationship between pain reports and physical pathology, and (2) the accuracy of pain recall has never been assessed in this population. The current study investigated the accuracy of endometriotic pain recall for pain experienced over a 30-day period, as well as potential psychological mediators of pain recall accuracy, including psychological wellbeing, distress specific to infertility, passive and active coping, and pain present at time of recall in 100 women with endometriosis. Findings indicated that women were relatively accurate in their recall of pain. Only passive coping and pain present at recall were predictive of accuracy, with greater passive coping and lower pain at recall predictive of overestimation of past pain. Study implications are discussed, including: (1) report of pain over a 30-day duration appears credible for the majority of patients with endometriosis and (2) women exhibiting greater passive coping may benefit from psychological treatment in addition to medical intervention. PMID- 17852654 TI - Midwives' experiences of encountering women seeking an abortion. AB - In order to gain knowledge about midwives' clinical and emotional experiences of working with termination of pregnancy (TOP) and their perception of women's motives for having an abortion questionnaires were mailed to a representative sample of Swedish midwives (n = 258), and 84% responded. Responses to 17 statements were studied and interpreted. It was found that every third midwife had not at all worked with TOP, and every fifth had not done so in the preceding two years. Among those who had experienced this work, few midwives had considered changing their job or had had misgivings or feelings of inadequacy caused by encountering women seeking an abortion. Both working currently with TOP and for a longer period of time were found to evoke positive experiences in every other midwife. Midwives' perception of motives for abortion corresponded very well to motives provided by women themselves. Half the midwives had had misgivings concerning late abortions and somewhat fewer regarding surgical abortions. In general, religious belief did not influence midwives' views of TOP. Those midwives who had themselves had an abortion reported fewer misgivings about late abortions than those without personal experience of TOP. PMID- 17852655 TI - Psychological and behavioural aspects of patients with Turner syndrome from childhood to adulthood: a review of the clinical literature. AB - Turner syndrome (TS) is a chromosomal abnormality, which occurs in approximately one of every 2500 female births. Short stature, infertility, additional physical abnormalities, skeletal and medical problems may be present. Genetic, hormonal, and medical problems associated with TS are likely to affect psychosexual development of female adolescent patients, and thus influence their psychological functioning, behavior patterns, social interactions and learning ability. Although TS constitutes a chronic medical condition, with possible physical, social and psychological complications in a woman's life, hormonal and estrogen replacement therapy and assisted reproduction, are treatments that can be helpful for TS patients and improve their quality of life. Authors report on a review of the research literature clinical aspects of the syndrome as well as the beneficial effect of hormonal therapy in such patients. PMID- 17852656 TI - Early adverse emotional response to childbirth in Turkey: the impact of maternal attachment styles and family support. AB - Early adverse emotional response which is often detected in the form of depressive symptoms is a predictor of postpartum depression following the birth. The aim of our study is to highlight contextual and individual factors that have an impact on mothers' depressive symptoms during the early postpartum period. One hundred mothers participated in the study. Maternal depressive symptoms were screened by Edinburgh Postpartum Depression Scale (EPDS), and maternal anxiety level was assessed by State-Trait Anxiety Inventory (STAI) at early postpartum period (7-10 days). The Multidimensional Scale of Perceived Social Support (MSPSS) was used for the assessment of maternal social support. The Adult Attachment Scale (AAS) was used to determine the attachment style of the mother. The mean EPDS score of mothers who live in extended families is found to be significantly lower than others who live in nuclear families (extended families 7.13+/-7.39, nuclear families 11.77+/-5.96, p=0.006). Significant positive correlations were found between EPDS total scores and ambivalent attachment style group (r=.0436, p=.000), and avoidant attachment style group (r=.328, p=.001). The level of perceived family support also showed a negative correlation with EPDS total score (r=-.363, p=.000). The regression of EPDS total score with ambivalent attachment style and state anxiety level are positively predicted and the level of perceived family support and existence of wider social network negatively predict the EPDS total score in the first postpartum week. Maternal attachment patterns, living with the extended family and existence of family support have an important impact on early postpartum emotional adaptation. Early intervention strategies should count towards these individual and contextual factors when designing screening and preventive interventions for postpartum depression. PMID- 17852657 TI - Mothers' views of their childbirth experience two years after term breech delivery. AB - INTRODUCTION: This study was performed to evaluate mothers' views of their childbirth experience two years after term breech delivery. METHODS: Two years after delivery mothers were asked to fill out a questionnaire concerning their breech birth experience and their view about the care provided to them while giving birth. Outcomes of the planned cesarean section (CS) group were compared with outcomes of the planned vaginal delivery (VD) group, whether or not a vaginal birth was realized or an emergency cesarean section was performed. Any differences were further analyzed by use of logistic regression, controlling for potential confounders. RESULTS: Significantly more women in the planned CS group were reassured about their baby's health (67.4% vs. 37.9%, p=0.0006) at the time of delivery, whereas more women in the planned VD group recalled having been worried about their baby's health at the time of delivery (45.0% vs. 25.6%, p=0.02). Also, more women in the planned VD group experienced more pain during labor and delivery than expected (46.9% vs. 18.5%, p=0.008). In the planned VD group fewer women indicated they had an active say in decision-making (59.1% vs. 85.3%, p=0.001). CONCLUSIONS: Evaluation of the mothers' views of their childbirth experience two years after term breech delivery showed that more women in the planned VD group recalled having been worried about their child's health at the time of delivery, experienced more pain than expected, and reported less involvement in decision-making. PMID- 17852658 TI - Service use data analysis of pre-pregnancy psychiatric and somatic diagnoses in women with hyperemesis gravidarum. AB - INTRODUCTION: The purpose of this study was to redress weaknesses in past studies of a psychogenic etiology for hyperemesis gravidarum (HG) by (1) estimating from a known population what proportion of HG cases also have psychiatric diagnoses, (2) determining if psychiatric disorder preceded HG, and (3) re-considering whether non-pregnancy somatic conditions also precede HG. METHODS: We analyzed insurance data for all 11,016 members who gave birth to singletons in 2000-2004, 208 of whom had HG. RESULTS: Prevalence of HG was 1.8% overall, 3.8% with one psychiatric diagnosis, 5.8% with >1 psychiatric diagnosis. One in 10 HG cases had pre-pregnancy depression, anxiety, or substance abuse diagnoses. One in five HG cases had either a psychiatric or a somatic condition (e.g., chronic pelvic pain, dysmenorrhea) diagnosis prior to pregnancy. Pre-pregnancy psychiatric diagnosis doubled the adjusted odds of HG. Combined psychiatric and somatic diagnoses quadrupled the adjusted odds of HG. DISCUSSION: Vomiting is a non-specific sign that may have multiple etiologies. For 10-20% of HG sufferers, vomiting may be a physical comorbidity of a psychiatric condition occurring in the context of pregnancy. Psychobiological research with HG cases with past or current psychiatric diagnoses is needed to consider plausible mechanisms. PMID- 17852659 TI - The Hyperemesis Beliefs Scale (HBS): a new instrument for assessing beliefs about severe nausea and vomiting in pregnancy. AB - OBJECTIVE: The purpose of this research was to validate the Hyperemesis Beliefs Scale (HBS), a new instrument for assessing patient perception factors of hyperemesis gravidarum (HG) that influence reported patient satisfaction with medical care. METHODS: Patients' beliefs and their perception of their physicians' beliefs about the causal explanations of HG, seriousness of the illness, and the impact of the illness upon patients' daily lives were determined using a newly developed hyperemesis beliefs scale (HBS) in a sample of 96 women. Exploratory factor analyses of the patient and physician versions of the HBS were performed separately using principal factor analysis extraction and oblique rotation in SPSS. RESULTS: Exploratory factor analyses of patient and physician versions of the HBS demonstrated broad support for the hypothesized factor structure. However, two key differences appeared in the two versions of the HBS. First, the patient items exhibited two causal factors (general and personal), whereas the physician items showed only a single causal factor. Second, in the patient version, items assessing the impact of HG on the babies' health loaded separately from the rest of the items in the HBS, whereas the analyses of the corresponding physician items indicated that the baby items loaded well on the degree of seriousness factor. CONCLUSION: This scale may be of value in facilitating further research on HG illness representations, patient-physician relationship and patient satisfaction. Specifically, the HBS design provides data to show whether patient-physician agreement on particular measures is associated with better patient satisfaction outcomes. PMID- 17852661 TI - Depression scores and associated factors in pregnant and non-pregnant women: a community-based study in Turkey. AB - The aims of this study were to evaluate and compare the depression scores of pregnant and non-pregnant women, and to identify the factors associated with depression scores in the two groups. This community-based study was conducted in a primary health care center catchment area in Ankara (population: 17,838) in January 2003. At the beginning of the study, the trimesters of all pregnant women (n = 66) were determined and as a control group (n = 138), two non-pregnant women matched for age and parity characteristics living in the same area were selected for each pregnant woman. Each participant completed a questionnaire and the Beck Depression Inventory (BDI). One-way ANOVA, univariate correlation, and multiple linear regression analyses were used in statistical evaluation. Depression scores of pregnant and non-pregnant women, and women at different trimesters of pregnancy were similar. Using a cut-off score > or = 18 on the BDI, 26.5% of non pregnant women, 27.3% of pregnant women, 25.0% of pregnant women in their first and second trimester, and 30.0% of third trimester pregnant women were found to be depressive. According to multiple linear regression analysis, age, age at marriage, and the number of people living in the home were associated with depression in both groups. Depression scores were similar in pregnant women and non-pregnant controls. There were different associations between depression score and the study groups' characteristics. PMID- 17852662 TI - The second leg home advantage: evidence from European football cup competitions. AB - The home advantage is a widely acknowledged sporting phenomenon, especially in association football. Here, we examine the second leg home advantage, an effect that is discussed in the public domain but which has received very little scientific attention. The second leg home advantage effect occurs when on average teams are more likely to win a two-stage knock-out competition when they play at home in the second leg. That is, both teams have a home advantage but this advantage is significantly greater for the team that plays at home second. Examining data from three different European Cup football competitions spanning 51 years, we show that the second leg home advantage is a real phenomenon. The second leg home team has more than a 50% probability to qualify for the next round in the competition even after controlling for extra time and team ability as possible alternative explanations. The second leg home advantage appears, however, to have decreased significantly over the past decade. Possible reasons for its existence and subsequent decline are presented. PMID- 17852663 TI - Perceptions of elite coaches and sports scientists of the research needs for elite coaching practice. AB - A major objective of sports scientists and elite coaches is the enhancement of athletic performance. Despite this common goal, there is a general perception that research in sports science does not meet the needs of coaches. A study using survey and interview examined the perceptions of elite coaches and sports science researchers in Australia regarding the research needs of elite coaching. Congruence was found between coaches and researchers regarding research practice at the elite level. Both groups held common perceptions on the importance and application of research, the methods by which research questions are determined, and the qualities valued in elite coaches and sports science researchers. However, elite coaches perceived a need for more research in the area of sports psychology, dissemination of research findings via coaching clinics and sports specific magazines, and the use of more appropriate "lay" language in information dissemination. PMID- 17852665 TI - Prediction of maximal oxygen uptake in sedentary males from a perceptually regulated, sub-maximal graded exercise test. AB - The purpose of this study was to assess the validity of predicting the maximal oxygen uptake (VO2(max)) of sedentary men from sub-maximal VO2 values obtained during a perceptually regulated exercise test. Thirteen healthy, sedentary males aged 29-52 years completed five graded exercise tests on a cycle ergometer. The first and fifth test involved a graded exercise test to determine VO2(max). The two maximal graded exercise tests were separated by three sub-maximal graded exercise tests, perceptually regulated at 3-min RPE intensities of 9, 11, 13, 15, and 17 on the Borg ratings of perceived exertion (RPE) scale, in that order. After confirmation that individual linear regression models provided the most appropriate fit to the data, the regression lines for the perceptual ranges 9-17, 9-15, and 11-17 were extrapolated to RPE 20 to predict VO2(max). There were no significant differences between VO2(max) values from the graded exercise tests (mean 43.9 ml x kg(-1) x min(-1), s = 6.3) and predicted VO2(max) values for the perceptual ranges 9-17 (40.7 ml x kg(-1) x min(-1), s = 2.2) and RPE 11-17 (42.5 ml x kg(-1) x min(-1), s = 2.3) across the three trials. The predicted VO2(max) from the perceptual range 9-15 was significantly lower (P < 0.05) (37.7 ml x kg( 1) x min(-1), s = 2.3). The intra-class correlation coefficients between actual and predicted VO2(max) for RPE 9-17 and RPE 11-17 across trials ranged from 0.80 to 0.87. Limits of agreement analysis on actual and predicted VO2 values (bias +/ 1.96 x S(diff)) were 3.4 ml x kg(-1) x min(-1) (+/- 10.7), 2.4 ml x kg(-1) x min(-1) (+/- 9.9), and 3.7 ml x kg(-1) x min(-1) (+/- 12.8) (trials 1, 2, and 3, respectively) of RPE range 9-17. Results suggest that a sub-maximal, perceptually guided graded exercise test provides acceptable estimates of VO2(max) in young to middle-aged sedentary males. PMID- 17852666 TI - The relationships between exercise intensity, heart rate, and blood pressure during an incremental isometric exercise test. AB - Currently, it is not possible to prescribe isometric exercise at an intensity that corresponds to given heart rates or systolic blood pressures. This might be useful in optimizing the effects of isometric exercise training. Therefore, the aim of this study was to explore the relationships between isometric exercise intensity and both heart rate and systolic blood pressure during repeated incremental isometric exercise tests. Fifteen participants performed seated isometric double-leg knee extension, during which maximum voluntary contraction (MVC) was assessed, using an isokinetic dynamometer. From this, a corresponding peak electromyographic activity (EMG(peak)) was determined. Subsequently, participants performed two incremental isometric exercise tests (at least 48 h apart) at 10, 15, 20, 25, and 30% EMG(peak), during which steady-state heart rate and systolic blood pressure were recorded. In all participants, there were linear relationships between %EMG(peak) and heart rate (r at least 0.91; P < 0.05) and between %EMG(peak) and systolic blood pressure (r at least 0.92; P < 0.05). Also, when repeated tests were compared, there were no differences in the slopes (P > 0.50) or elevations (P > 0.10) for either of the relationships. Therefore, these linear relationships could be used to identify isometric exercise training intensities that correspond to precise heart rates or systolic blood pressures. Training performed in this way might provide greater insight into the underlying mechanisms for the cardiovascular adaptations that are known to occur as a result. PMID- 17852668 TI - Comparison of two Actigraph models for assessing free-living physical activity in Indian adolescents. AB - This aim of this study was to compare the new Actigraph (GT1M) with the widely used Model 7164. Seven days of free-living physical activity were measured simultaneously using both the Model 7164 and GT1M in 30 Indian adolescents (mean age 15.8 years, s = 0.6). The GT1M was on average 9% lower per epoch than model 7164, thus a correction factor of 0.91 is suggested for comparison between the two monitors. The differences between monitors increased in magnitude with intensity of activity (P < 0.001) but remained randomly distributed (r = 0.01, P = 0.96). No significant difference was observed between monitors for time spent in moderate (P = 0.31) and vigorous (P = 0.34) physical activity when using the same epoch length. The Model 7164 classified less time as sedentary (P < 0.001) and more time as light-intensity activity (P < 0.001) than the GT1M. In conclusion, data from the GT1M can be compared with historical data using average counts per minute with a correction factor, and the two models might be comparable for assessing time spent in moderate to vigorous physical activity in children when using the same epoch length. PMID- 17852669 TI - Stressors, coping, and coping effectiveness: gender, type of sport, and skill differences. AB - The aim of this study was to examine stressors, coping, and coping effectiveness as a function of gender, type of sport, and skill. The sample consisted of 749 undergraduate athletes (455 males, 294 females) aged 18-38 years (mean= 19.8 years). Skill was classified as international/national, county, university, and club standard. Participants completed a stressor and coping concept map (Novak & Gowin, 1984). The results revealed gender, type of sport, and skill differences in relation to stressor frequencies, coping strategy deployment, and coping effectiveness. In contrast to previous research, females used a variety of problem-focused (e.g. planning, communication, technique-orientated coping) strategies more frequently than males. Team sport athletes reported a variety of sport-specific stressors relating to the demands of playing in a team environment. The group of national/international athletes reported using more planning, blocking, and visualization, and also reported that their coping was more effective than that of less-skilled athletes. PMID- 17852670 TI - Post-exercise ingestion of a unique, high molecular weight glucose polymer solution improves performance during a subsequent bout of cycling exercise. AB - The aim of the present study was to determine the effect of post-exercise ingestion of a unique, high molecular weight glucose polymer solution, known to augment gastric emptying and post-exercise muscle glycogen re-synthesis, on performance during a subsequent bout of intense exercise. On three randomized visits, eight healthy men cycled to exhaustion at 73.0% (s = 1.3) maximal oxygen uptake (90 min, s = 15). Immediately after this, participants consumed a one litre solution containing sugar-free flavoured water (control), 100 g of a low molecular weight glucose polymer or 100 g of a very high molecular weight glucose polymer, and rested on a bed for 2 h. After recovery, a 15-min time-trial was performed on a cycle ergometer, during which work output was determined. Post exercise ingestion of the very high molecular weight glucose polymer solution resulted in faster and greater increases in blood glucose (P < 0.001) and serum insulin (P < 0.01) concentrations than the low molecular weight glucose polymer solution, and greater work output during the 15-min time-trial (164.1 kJ, s = 21.1) than both the sugar-free flavoured water (137.5 kJ, s = 24.2; P < 0.05) and the low molecular weight glucose polymer (149.4 kJ, s = 21.8; P < 0.05) solutions. These findings could be of practical importance for athletes wishing to optimize performance by facilitating rapid re-synthesis of the muscle glycogen store during recovery following prolonged sub-maximal exercise. PMID- 17852671 TI - The development and maintenance of mental toughness: perceptions of elite performers. AB - Seven participants from a previous study (Jones, Hanton, & Connaughton, 2002) agreed to be interviewed about the development of mental toughness. We also aimed to determine whether mental toughness requires maintenance. Semistructured interviews were conducted to elicit the participants' perceptions of how mental toughness is cultivated and retained. Findings indicated that the development of mental toughness is a long-term process that encompasses a multitude of underlying mechanisms that operate in a combined, rather than independent, fashion. In general, these perceived underlying mechanisms related to many features associated with a motivational climate (e.g. enjoyment, mastery), various individuals (i.e. coaches, peers, parents, grandparents, siblings, senior athletes, sport psychologists, team-mates), experiences in and outside sport, psychological skills and strategies, and an insatiable desire and internalized motives to succeed. It was also reported that once mental toughness had been developed, three perceived underlying mechanisms were required to maintain this construct: a desire and motivation to succeed that was insatiable and internalized, a support network that included sporting and non-sporting personnel, and effective use of basic and advanced psychological skills. Practical implications and future avenues of research are discussed. PMID- 17852672 TI - Indoor 16.1-km time-trial performance in cyclists aged 25- 63 years. AB - In this study, we assessed age-related changes in indoor 16.1-km cycling time trial performance in 40 competitive male cyclists aged 25-63 years. Participants completed two tests: (1) a maximal ramped Kingcycle ergometer test, with maximal ramped minute power (RMPmax, W) recorded as the highest mean external power during any 60 s and maximal heart rate (HRmax, beats min(-1)) as the highest value during the test; and (2) an indoor Kingcycle 16.1-km time-trial with mean external power output (W), heart rate (beats min(-1)), and pedal cadence (rev min(-1)) recorded throughout the event. Results revealed age-related declines (P < 0.05) in absolute and relative time-trial external power output [(24 W (7.0%) per decade], heart rate [7 beats min(-1) (3.87%) per decade], and cadence [3 rev min(-1) (3.1%) per decade]. No relationships (P > 0.05) were observed for mean power output and heart rate recorded during the time-trial versus age when expressed relative to maximal ramped minute power and maximal heart rate respectively. Strong relationships (P < 0.05) were observed for maximal ramped minute power and time-trial power (r= 0.95) and for maximal heart rate and time trial heart rate (r= 0.95). Our results show that indoor 16.1-km time-trial performance declines with age but relative exercise intensity (%RMPmax and %HRmax) does not change. PMID- 17852673 TI - Gross cycling efficiency is not altered with and without toe-clips. AB - The aim of this study was to examine the claim that reductions of 8-18% in submaximal oxygen consumption (VO2) could be due to changing components on a Monark ergometer, from standard pedals without toe-clips or straps (flat pedals) to racing pedals of that era, which included toe-clips and straps (toe-clip pedals). This previously untested assertion was evaluated using 11 males (mean age 22.3 years, s= 1.2; height 1.82 m, s= 0.07; body mass 82.6 kg, s= 8.8) who completed four trials in a randomized, counterbalanced order at 60 rev min(-1) on a Monark cycle ergometer. Two trials were completed on flat pedals and two trials on toe-clip pedals. The Douglas bag method was used to assess VO2 and gross efficiency during successive 5-min workloads of 60, 120, 180, and 240 W. The mean VO2 was 2.1% higher for toe-clip pedals than flat pedals and there was a 99% probability that toe-clip pedals would not result in an 8% lower VO2. These results indicate that toe-clip pedals do not reduce VO2. PMID- 17852674 TI - Ability of test measures to predict competitive performance in elite swimmers. AB - The purpose of this study was to quantify the relationship between changes in test measures and changes in competition performance for individual elite swimmers. The 24 male and 16 female swimmers, who were monitored for 3.6 years (s = 2.5), raced in a major competition at the end of each 6-month season (3.6 competitions, s = 2.2). A 7 x 200-m incremental swimming step-test and anthropometry were conducted in up to four training phases each season. Correlations of changes in step-test and anthropometry measures between training phases and seasons with changes in competition performance between seasons were derived with repeated-measures mixed-modelling and linear regression. Changes in competition performance were best tracked by changes in test measures between taper phases. The best single predictor of competition performance was skinfolds for females (r = -0.53). The best predictor from the step-test was stroke rate at a blood lactate concentration of 4 mmol x l(-1) (females: r = 0.46; males: r = 0.41); inclusion of the second-best step-test predictor in a multiple linear regression improved the correlations (females: r = 0.52 with speed in the seventh step included; males: r = 0.58 with peak lactate concentration included). In conclusion, a combination of fitness and technique factors is important for competitive performance. The step-test is a useful adjunct in a swimmer's training preparation for tracking large changes in performance. PMID- 17852675 TI - Effects of crowd size on referee decisions: analysis of the FA Cup. AB - Data were collected on the number of first yellow cards awarded during 857 games, over six seasons (1996 - 2002), played in the Football Association (FA) Cup. Overall, a significantly higher number of yellow cards were awarded against the away team, while a non-linear relationship between crowd size and yellow cards was observed. In general, the probability of a yellow card being awarded against the home team decreased as crowd size increased, but was attenuated for the largest crowd sizes. Crowd size may be related to the probability of the home team receiving a yellow card in two potential ways. Crowd noise may be a decision making heuristic whereby the likelihood that an incident is a foul is increased when accompanied by crowd noise. Alternatively, referees may seek to appease the crowd and are more likely to do so as crowd size increases. The present findings have implications for the training of match officials and for coaches and players as they prepare to play away from home. PMID- 17852676 TI - The influence of game location and outcome on behaviour and mood states among professional rugby league players. AB - In this study, we examined the relationship between home and away matches on mood. In addition, the relationships between game location, game outcome, behavioural factors, and mood were investigated among 12 professional English rugby league players competing in the Super League. Participants completed daily diaries for 27 days. The diary consisted of six analogue scales measuring mood (relaxed-tense, energetic-weary, depressed-elated, tired-alert, anxious-calm, cheerful-miserable) as well as behavioural factors and self-rated performance. There were no significant differences in self-reported mood states leading up to home or away matches except for players feeling more tired when playing away. Significant relationships between mood and behaviours (e.g. sleep and eating) and subjective performance were observed. The outcome of the match was found to influence mood, with a defeat resulting in decreased mood. Our results show that game location did not influence mood and therefore does not provide an explanation for the home advantage. PMID- 17852677 TI - Assessing pitcher and catcher influences on base stealing in Major League Baseball. AB - A formal statistical analysis is performed to determine the extent to which pitchers and catchers can influence stolen-base attempts and successes. Two response proportions, attempt/opportunity and success/attempt, are modelled separately using mixed-effects logistic regression models applied to situations with a runner on first and other bases empty. Data include the first innings of all Major League Baseball games played between 1978 and 1990, which encompasses over 48,000 opportunities and 9000 attempts. Pitchers and catchers are entered as random effects and various other factors thought to influence stolen-base attempts and successes are entered as fixed effects. Variance components are estimated and hypotheses tests indicate that the population variance components for both pitchers and catchers are significant for both response proportions. The presence of variation among players at the respective positions is interpreted as evidence that stolen-base defence is a real skill exhibited to varying extents by different players. Furthermore, the variance component for pitchers is greater than that for catchers for both response proportions, indicating that pitchers have greater potential to affect stolen-base attempts and successes. Under usual conditions, it is estimated that 95% of pitchers have first-inning stolen-base success/attempt probabilities between 0.50 and 0.84, while 95% of catchers have probabilities between 0.59 and 0.79. PMID- 17852678 TI - Track compliance does not affect sprinting performance. AB - The aim of this study was to test the hypothesis that sprint performance (time over a given distance) would be affected by track compliance, with better performances on the more compliant surface. Ten sprinters participated in the study. The athletes performed maximal sprints (60 m) on three different track configurations (hard, 5500 kN m(-1); soft, 2200 kN m(-1); spring, 550 kN m(-1)). A 60-m single-lane running surface was constructed. Plywood boards (1.2 cm thick) were placed on a 60 x 0.6 m wooden chipboard frame serving as the base surface. All participants ran two times on each track configuration in a randomized order. The athletes' kinematics were recorded using the Vicon 624 system with 12 cameras operating at 250 Hz. Four Kistler force plates (1250 Hz) were used to record ground reaction forces. Sprint performance (time over 60 m) was unaffected by the different track compliances (P= 0.57). In addition, there was no effect of track (P> 0.05) on the sprinting kinematics and kinetics of the ankle or knee joint. The hypothesis that sprint performance is affected by track compliance can be rejected because the sprinters recorded similar performances while sprinting over 60 m on all three track configurations. We conclude that: (1) the possible deformation of the track while sprinting is minor enough not to cause a specific adjustment in the leg mechanics affecting the effectiveness of the stretch shortening cycle of the sprinters; and (2) the energy exchange between sprinters and tracks has only a marginal effect on sprint performance due to its small magnitude. More research on tracks with lower stiffness is required. PMID- 17852679 TI - Effects of time of day and distance upon accuracy and consistency of throwing darts. AB - We examined variations in dart-throwing performance during the daytime in 12 participants. Two distances from the dartboard were investigated - the normal distance (short throws) and another 50% further away than this (long throws). Intra-aural temperature and subjective fatigue were measured, and errors in performance were assessed as the radial distances of throws from the bulls-eye and the standard deviation of these distances. Long-distance throws improved significantly throughout the daytime and correlated positively with intra-aural temperature (r= -0.49, P=0.002 and r= -0.49, P=0.002 for errors and standard deviation of errors, respectively), but not with subjective fatigue (r= -0.10, P=0.56 and r= -0.05, P=0.74 for errors and standard deviation of errors, respectively). Short-distance throws were associated less with intra-aural temperature (r= -0.46, P= 0.005 and r= -0.17, P=0.31 for errors and standard deviation of errors, respectively), and worsened with fatigue (r=+0.34, P= 0.040 for errors). Compared with the short-distance throws, the long-distance throws were performed significantly less well than could be accounted for by the increased distance (mean errors were increased 1.67-2.78 times and standard deviation of errors of errors 1.58-3.68 times), supporting the concept of a trade off between force of contraction and accuracy of performance. Throwing darts can be used as a model for investigating factors that influence motor performance, and our results indicate that the effects of time of day upon performance depend upon the relative importance of force and accuracy. PMID- 17852680 TI - Anthropometric characteristics of elite cricket fast bowlers. AB - The aims of this study were to describe the current anthropometric profiles of elite Australian female and male cricket fast bowlers and establish a set of reference values useful for future investigations on player selection, talent identification, and training programme development. The participants were 26 female (mean age 22.5 years, s = 4.5; height 1.71 m, s = 0.05; body mass 66.2 kg, s = 7.5) and 26 male (mean age 23.9 years, s = 3.5; height 1.88 m, s = 0.05; body mass 87.9 kg, s = 8.2) fast bowlers. The anthropometric profiles included the measurement of skinfolds, and segment lengths, breadths, and girths. A series of derived variables assessing the distribution of subcutaneous adipose tissue, the bivariate overlap zone, relative body size and proportionality, and somatotype were also calculated. The male bowlers had larger length, breadth, and girth measurements than their female counterparts. There were differences in proportionality between the sexes, with only the male bowlers exhibiting characteristics that could be considered "large" relative to height. The female bowlers had a higher sum of seven skinfolds (P < 0.001), were more endomorphic (F(1,50) = 30.18, P < 0.001), and less mesomorphic (F(1,50 = 10.85, P < 0.01) than the male bowlers. These reference data should be useful to practitioners and researchers interested in cricket. Further research is needed to clarify why only male fast bowlers had variables that were proportionally large relative to height. PMID- 17852681 TI - Intensity of exercise recovery, blood lactate disappearance, and subsequent swimming performance. AB - The aim of this study was to examine the effects of active versus passive recovery on blood lactate disappearance and subsequent maximal performance in competitive swimmers. Fourteen male swimmers from the University of Virginia swim team (mean age 20.3 years, s= 4.1; stature 1.85 m, s= 2.2; body mass 81.1 kg, s= 5.6) completed a lactate profiling session during which the speed at the lactate threshold (V(LT)), the speed at 50% of the lactate threshold (V(LT.5)), and the speed at 150% of the lactate threshold (V(LT1.5)) were determined. Participants also completed four randomly assigned experimental sessions that consisted of a 200-yard maximal-effort swim followed by 10 min of recovery (passive, V(LT.5), V(LT), V(LT1.5)) and a subsequent 200-yard maximal effort swim. All active recovery sessions resulted in greater lactate disappearance than passive recovery (P < 0.0001 for all comparisons), with the greatest lactate disappearance associated with recovery at V(LT) (P= 0.006 and 0.007 vs. V(LT.5) and V(LT1.5) respectively) [blood lactate disappearance was 2.1 mmol l(-1) (s= 2.0), 6.0 mmol l(-1) (s=2.6), 8.5 mmol l(-1) (s= 1.8), and 6.1 mmol l(-1) (s= 2.5) for passive, V(LT.5), V(LT), and V(LT1.5) respectively]. Active recovery at VLT and V(LT1.5) resulted in faster performance on time trial 2 than passive recovery (P=0.005 and 0.03 respectively); however, only active recovery at V(LT) resulted in improved performance on time trial 2 (TT2) relative to time trial 1 (TT1) [TT2- TT1: passive +1.32 s (s= 0.64), V(LT.5) +1.01 s (s= 0.53), V(LT) -1.67 s (s= 0.26), V(LT1.5) -0.07 s (s = 0.51); P < 0.0001 for V(LT)). In conclusion, active recovery at the speed associated with the lactate threshold resulted in the greatest lactate disappearance and in improved subsequent performance in all 14 swimmers. Our results suggest that coaches should consider incorporating recovery at the speed at the lactate threshold during competition and perhaps during hard training sessions. PMID- 17852682 TI - Reliability and validity of two tests of soccer skill. AB - Twenty-four players from the 1st/2nd (elite) and 24 players from the 3rd/4th (non elite) university football teams were recruited to evaluate the Loughborough Soccer Passing Test (LSPT) and Loughborough Soccer Shooting Test (LSST) as tools to assess soccer skill. The LSPT requires players to complete 16 passes as quickly as possible. The LSST requires players to pass, control, and shoot the ball to targets on a full-sized goal. Participants completed two main trials each separated by at least one day. During both trials, the participants were given practice efforts before recording the mean of the next two (LSPT) or 10 (LSST) attempts as the performance score. For the LSPT, the mean time taken, added penalty time, and overall performance time were less in the elite players (elite: 43.6 s, s = 3.8; non-elite: 52.5 s, s= 7.4; P= 0.0001). For the LSST, there was no difference in the mean points scored per shot between groups (elite: 1.34, s = 0.46; non-elite: 1.28, s = 0.53). However, the elite players had higher mean shot speed (elite: 80 km h(-1), s = 4.5; non-elite: 74 km h(-1), s = 4.2; P < 0.0001) and performed each shot sequence faster (elite: 7.87 s, s= 0.29; non-elite: 8.07 s, s= 0.35; P= 0.037) than the non-elite players. Performance on both tests was more repeatable in elite players. In conclusion, the LSPT and LSST are valid and reliable protocols to assess differences in soccer skill performance. PMID- 17852683 TI - The effects of work:rest duration on physiological and perceptual responses during intermittent exercise and performance. AB - In this study, we examined the effects of different work:rest durations during 20 min intermittent treadmill running and subsequent performance. Nine males (mean age 25.8 years, s = 6.8; body mass 73.9 kg, s = 8.8; stature 1.75 m, s = 0.05; VO(2max) 55.5 ml x kg(-1) x min(-1), s = 5.8) undertook repeated sprints at 120% of the speed at which VO(2max) was attained interspersed with passive recovery. The work:rest ratio was constant (1:1.5) with trials involving either short (6:9 s) or long (24:36 s) work:rest exercise protocols (total exercise time 8 min). Each trial was followed by a performance run to volitional exhaustion at the same running speed. Testing order was randomized and counterbalanced. Heart rate, oxygen consumption, respiratory exchange ratio, and blood glucose were similar between trials (P > 0.05). Blood lactate concentration was greater during the long than the short exercise protocol (P < 0.05), whereas blood pH was lower during the long than the short exercise protocol (7.28, s = 0.11 and 7.30, s = 0.03 at 20 min, respectively; P < 0.05). Perceptions of effort were greater throughout exercise for the long than the short exercise protocol (16.6, s = 1.4 and 15.1, s = 1.6 at 20 min, respectively; P < 0.05) and correlated with blood lactate (r = 0.43) and bicarbonate concentrations (r = 0.59; P < 0.05). Although blood lactate concentration at 20 min was related to performance time (r = - 0.56; P < 0.05), no differences were observed between trials for time to exhaustion (short exercise protocol: 95.8 s, s = 30.0; long exercise protocol: 92.0 s, s = 37.1) or physiological responses at exhaustion (P > 0.05). Our results demonstrate that 20 min of intermittent exercise involving a long work:rest duration elicits greater metabolic and perceptual strain than intermittent exercise undertaken with a short work:rest duration but does not affect subsequent run time to exhaustion. PMID- 17852684 TI - Morphology of the deltoid muscles in elite tennis players. AB - The aim of this study was to examine the deltoid muscle properties of the dominant and non-dominant arm of Greek professional male tennis players. Eight male tennis players (mean age 22.0 years, s = 3.2) were subjected to biopsy of the deltoid muscle of both arms. Adenosine triphosphate (ATPase) histochemistry and myosin heavy chain (MHC) composition were performed on the samples with homogenate electrophoresis. No significant differences were observed in the percentage of types I, IIa, IIab, and IIb muscle fibres between the deltoid muscles of the two arms. Types I, IIa, and IIx muscle fibres of the dominant and non-dominant deltoid muscles did not differ significantly for MHC isoform composition. Type IIab muscle fibres showed a similar cross-sectional area (CSA) percentage distribution between the two arms. The CSA percentage for types I, IIa, and IIb muscle fibers did not differ significantly between the dominant and the non-dominant arm. We conclude therefore that regular tennis training probably does not lead to any significant changes in the muscle fibre types of the dominant and non-dominant arms of elite tennis players. PMID- 17852685 TI - Effect of toss and weather on County Cricket Championship outcomes. AB - The principal competition in English professional cricket has become more competitive with the introduction of hierarchical divisions linked by promotion and relegation. Using regression analysis, we examine the effect on league points when teams suffer different degrees of weather disruption over the season and different amounts of luck in winning the toss for choice of first innings. The results are used to illustrate the sensitivity of championship, promotion, and relegation outcomes to such matters of chance and revised league tables are produced after applying adjustments to account for the influence of weather and toss. Policy recommendations are presented on how the influence of weather and toss might be lessened in future seasons. PMID- 17852686 TI - Optimization of oar blade design for improved performance in rowing. AB - The aim of the present study was to find a more optimal blade design for rowing performance than the Big Blade, which has been shown to be less than optimal for propulsion. As well as the Big Blade, a flat Big Blade, a flat rectangular blade, and a rectangular blade with the same curvature and projected area as the Big Blade were tested in a water flume to determine their fluid dynamic characteristics at the full range of angles at which the oar blade might present itself to the water. Similarities were observed between the flat Big Blade and rectangular blades. However, the curved rectangular blade generated significantly more lift in the angle range 0-90 degrees than the curved Big Blade, although it was similar between 90 and 180 degrees. This difference was attributed to the shape of the upper and lower edges of the blade and their influence on the fluid flow around the blade. Although the influence of oar blade design on boat speed was not investigated here, the significant increases in fluid force coefficients for the curved rectangular blade suggest that this new oar blade design could elicit a practically significant improvement in rowing performance. PMID- 17852687 TI - Energy balance of locomotion with pedal-driven watercraft. AB - In this study, we examined the mechanics and energetics of locomotion with a paddle-wheel boat and a water bike. Power output (Wtot) was measured directly on the water bike by means of an instrumented chain-ring. The simultaneous assessment of oxygen uptake (VO2) allowed the computation of the "overall" efficiency of locomotion (etao = Wtot/VO2). Mean etao was 0.27 (s = 0.02), which was unaffected by the speed, and was assumed to be the same for the two boats as both are semi-recumbent bicycles. For the paddle-wheel boat, Wtot was then obtained from etao and measures of VO2. The power to overcome (passive) drag was calculated as Wd = D x v (where D is the force measured by means of a load cell when towing the boats at given speeds). Propelling efficiency was calculated as etap = Wd/Wtot, which was lower with the paddle-wheel boat (mean 0.35, s = 0.01) than with the water bike (mean 0.57, s = 0.01). The observed differences in etap and Wd explain why at the highest speed tested (approximately 3 m s(-1), the energy required to cover a unit distance with the water bike is similar to that required to move the paddle-wheel boat at 1.3 m s-1). PMID- 17852688 TI - Elite football on artificial turf versus natural grass: movement patterns, technical standards, and player impressions. AB - The aim of the present study was to examine the movement patterns, ball skills, and the impressions of Swedish elite football players during competitive games on artificial turf and natural grass. Time - motion analyses (36 observations) and technical analyses (16 team observations) were performed and 72 male and 21 female players completed a questionnaire. No differences were observed between artificial turf and natural grass in terms of total distance covered (mean 10.19 km, s = 0.19 vs. 10.33 km, s = 0.23), high-intensity running (1.86 km, s = 0.10 vs. 1.87 km, s = 0.14), number of sprints (21, s = 1 vs. 22, s = 2), standing tackles (10, s = 1 vs. 11, s = 1) or headers per game (8, s = 1 vs. 8, s = 1), whereas there were fewer sliding tackles (P < 0.05) on artificial turf than natural grass (2.1, s = 0.5 vs. 4.3, s = 0.6). There were more short passes (218, s = 14 vs. 167, s = 12) and midfield-to-midfield passes (148, s = 11 vs. 107, s = 8) (both P < 0.05) on artificial turf than natural grass. On a scale of 0-10, where 0 = "better than", 5 = "equal to", and 10 = "worse than", the male players reported a negative overall impression (8.3, s = 0.2), poorer ball control (7.3, s = 0.3), and greater physical effort (7.2, s = 0.2) on artificial turf than natural grass. In conclusion, the running activities and technical standard were similar during games on artificial turf and natural grass. However, fewer sliding tackles and more short passes were performed during games on artificial turf. The observed change in playing style could partly explain the male players' negative impression of artificial turf. PMID- 17852689 TI - What static and dynamic properties should slalom skis possess? Judgements by advanced and expert skiers. AB - Flexural and torsional rigidity are important properties of skis. However, the flexural and torsional rigidity that lead to optimal performance remain to be established. In the present study, four pairs of slalom skis that differed in flexural and torsional rigidity were tested by advanced and expert skiers. Using a 10-item questionnaire, different aspects of the skis' performance were rated on a 9-point scale. For each pair of skis, physical measurements were compared with the ratings of the two groups of skiers. Correlations (Spearman) were then determined between (i) different mechanical properties of the skis (static and dynamic), (ii) subjective assessments of the participants, and (iii) properties of the skis and the participants' assessments. The latter showed that expert skiers rate the aspects of the skis more accurately than advanced skiers. Most importantly, expert skiers are particularly sensitive to torsion of the skis. These results suggest that such highly rated elements should be addressed in future ski designs. PMID- 17852690 TI - The respiratory time and flow profile at volitional exercise termination. AB - In this study, we examine the effect of exercise on the time and flow characteristics of the respiratory cycle profile at the point of volitional exercise termination. Eight males (mean age 29 years, s = 10; body mass 74 kg, s = 7; height 1.75 m, s = 0.04) undertook a cycle test to volitional exhaustion on a cycle ergometer, which allowed peak oxygen uptake (VO(2peak)) to be measured (mean 51 ml x kg(-1) x min(-1), s = 7). At a later date, two sub-maximal tests to volitional exhaustion were completed in a random order at 76% (s = 6) and 86% VO(2peak) (s = 7). As expected, the magnitude of the respiratory flow and time characteristics varied with the three exercise intensities, as did the point of exercise termination and terminal ventilation rates, which varied from 7 to 27 min and 112 to 132 litres x min(-1) respectively. More importantly, however, at exercise termination some of the characteristics were similar, particularly the breathing frequency (at termination 49 breaths x min(-1)), the ratio between inspiration and total breath time (0.5), and the later occurrence of peak inspiratory flow (0.24-0.48 s). The coincident unity of these time and flow profile characteristics at exercise termination illustrates how the integration of timing and flow during breathing influence exercise capacity in non-elite athletes. PMID- 17852691 TI - The role of a short post-lunch nap in improving cognitive, motor, and sprint performance in participants with partial sleep deprivation. AB - The aim of this study was to determine the effects of a post-lunch nap on subjective alertness and performance following partial sleep loss. Ten healthy males (mean age 23.3 years, s = 3.4) either napped or sat quietly from 13:00 to 13:30 h after a night of shortened sleep (sleep 23:00-03:00 h only). Thirty minutes after the afternoon nap or control (no-nap) condition, alertness, short term memory, intra-aural temperature, heart rate, choice reaction time, grip strength, and times for 2-m and 20-m sprints were recorded. The afternoon nap lowered heart rate and intra-aural temperature. Alertness, sleepiness, short-term memory, and accuracy at the 8-choice reaction time test were improved by napping (P < 0.05), but mean reaction times and grip strength were not affected (P > 0.05). Sprint times were improved. Mean time for the 2-m sprints fell from 1.060 s (s(x) = 0.018) to 1.019 s (s(x) = 0.019) (P = 0.031 paired t-test); mean time for the 20-m sprints fell from 3.971 s (s(x) = 0.054) to 3.878 s (s(x) = 0.047) (P = 0.013). These results indicate that a post-lunch nap improves alertness and aspects of mental and physical performance following partial sleep loss, and have implications for athletes with restricted sleep during training or before competition. PMID- 17852692 TI - Relationships between sprinting, agility, and jump ability in female athletes. AB - The aim of this study was to assess the relationships between various field tests in female athletes. Altogether, 83 high school soccer, 51 college soccer, and 79 college lacrosse athletes completed tests for linear sprinting, countermovement jump, and agility in a single session. Linear sprints (9.1, 18.3, 27.4, and 36.6 m) and agility tests (Illinois and pro-agility) were evaluated using infrared timing gates, while countermovement jump height was assessed using an electronic timing mat. Pearson's product-moment correlation coefficients (r) were used to determine the strength and directionality of the relationship between tests and coefficients of determination (r2) were used to examine the amount of explained variance between tests. All of the performance scores were statistically correlated with each other; however, the coefficients of determination were low, moderate, and high depending on the test pairing. Linear sprint split times were strongly correlated with each other (r= 0.775 to 0.991). The relationship between countermovement jump height and linear sprinting was stronger with the longer distances (27.4 and 36.6 m) than with the shorter distances (9.1 and 18.3 m), and showed a stronger relationship within the college athletes (r= -0.658 to -0.788) than high school soccer players (r= -0.491 to -0.580). The Illinois and pro agility tests were correlated (r > or = 0.600) with each other as well as with linear sprint times. The results of this study indicate that linear sprinting, agility, and vertical jumping are independent locomotor skills and suggest a variety of tests ought to be included in an assessment protocol for high school and college female athletes. PMID- 17852693 TI - The role of upper torso and pelvis rotation in driving performance during the golf swing. AB - While the role of the upper torso and pelvis in driving performance is anecdotally appreciated by golf instructors, their actual biomechanical role is unclear. The aims of this study were to describe upper torso and pelvis rotation and velocity during the golf swing and determine their role in ball velocity. One hundred recreational golfers underwent a biomechanical golf swing analysis using their own driver. Upper torso and pelvic rotation and velocity, and torso-pelvic separation and velocity, were measured for each swing. Ball velocity was assessed with a golf launch monitor. Group differences (groups based on ball velocity) and moderate relationships (r > or = 0.50; P < 0.001) were observed between an increase in ball velocity and the following variables: increased torso-pelvic separation at the top of the swing, maximum torso-pelvic separation, maximum upper torso rotation velocity, upper torso rotational velocity at lead arm parallel and last 40 ms before impact, maximum torso-pelvic separation velocity and torso-pelvic separation velocity at both lead arm parallel and at the last 40 ms before impact. Torso-pelvic separation contributes to greater upper torso rotation velocity and torso-pelvic separation velocity during the downswing, ultimately contributing to greater ball velocity. Golf instructors can consider increasing ball velocity by maximizing separation between the upper torso and pelvis at the top of and initiation of the downswing. PMID- 17852694 TI - The influence of carbohydrate and protein ingestion during recovery from prolonged exercise on subsequent endurance performance. AB - Ingesting carbohydrate plus protein following prolonged exercise may restore exercise capacity more effectively than ingestion of carbohydrate alone. The objective of the present study was to determine whether this potential benefit is a consequence of the protein fraction per se or simply due to the additional energy it provides. Six active males participated in three trials, each involving a 90-min treadmill run at 70% maximal oxygen uptake (run 1) followed by a 4-h recovery. At 30-min intervals during recovery, participants ingested solutions containing: (1) 0.8 g carbohydrate x kg body mass (BM)(-1) h(-1) plus 0.3 g kg( 1) h(-1) of whey protein isolate (CHO-PRO); (2) 0.8 g carbohydrate x kg BM(-1) h( 1) (CHO); or (3) 1.1 g carbohydrate x kg BM(-1) h(-1) (CHO-CHO). The latter two solutions matched the CHO-PRO solution for carbohydrate and for energy, respectively. Following recovery, participants ran to exhaustion at 70% maximal oxygen uptake (run 2). Exercise capacity during run 2 was greater following ingestion of CHO-PRO and CHO-CHO than following ingestion of CHO (P< or = 0.05) with no significant difference between the CHO-PRO and CHO-CHO treatments. In conclusion, increasing the energy content of these recovery solutions extended run time to exhaustion, irrespective of whether the additional energy originated from sucrose or whey protein isolate. PMID- 17852695 TI - Changes in jump performance and muscle activity following soccer-specific exercise. AB - The jump performance of ten youth soccer players (mean age 15.8 years, s= 0.4) was assessed before and after 42 min of soccer-specific exercise performed on a non-motorized treadmill. A squat, countermovement, and drop jump were performed on a force platform and simultaneously surface EMG activity of four lower limb muscles was collected. Jump height deteriorated across all conditions with mean reductions of - 1.4 cm (s = 1.6; P < 0.05), - 3.0 cm (s = 2.9; P < 0.05), and 2.3 cm (s = 1.7; P < 0.01) in the squat, countermovement, and drop jump respectively. The impact force in the drop jump was the only force variable to show a significant change with fatigue (P < 0.05). Following the prolonged exercise, reductions in total muscle activity were non-significant for the squat jump, approached significance for the counter-ovement jump (P = 0.07), and achieved significance for the drop jump (P < 0.05). The results showed that completing soccer-specific exercise reduced performance in all jump tasks. Reductions in muscle activity were greatest for the drop jump, suggesting an influence of muscle stretch and loading on reduced muscle activity when fatigued. PMID- 17852696 TI - Relationships between training load, injury, and fitness in sub-elite collision sport athletes. AB - The purpose of this study was to develop statistical models that estimate the influence of training load on training injury and physical fitness in collision sport athletes. The incidence of training injuries was studied in 183 rugby league players over two competitive seasons. Participants were assessed for height, body mass, skinfold thickness, vertical jump, 10-m, 20-m and 40-m sprint time, agility, and estimated maximal aerobic power in the off-season, pre-season, mid-season, and end-season. Training load and injury data were summarised into pre-season, early-competition, and late-competition training phases. Individual training load, fitness, and injury data were modelled using a logistic regression model with a binomial distribution and logit link function, while team training load and injury data were modelled using a linear regression model. While physical fitness improved with training, there was no association (P=0.16-0.99) between training load and changes in physical fitness during any of the training phases. However, increases in training load during the early-competition training phase decreased (P= 0.04) agility performance. A relationship (P= 0.01-0.04) was observed between the log of training load and odds of injury during each training phase, resulting in a 1.50 - 2.85 increase in the odds of injury for each arbitrary unit increase in training load. Furthermore, during the pre-season training phase there was a relationship (P= 0.01) between training load and injury incidence within the training load range of 155 and 590 arbitrary units. During the early and late-competition training phases, increases in training load of 175-620 arbitrary units and 145-410 arbitrary units, respectively, resulted in no further increase in injury incidence. These findings demonstrate that increases in training load, particularly during the pre-season training phase, increase the odds of injury in collision sport athletes. However, while increases in training load from 175 to 620 arbitrary units during the early-competition training phase result in no further increase in injury incidence, marked reductions in agility performances can occur. These findings suggest that reductions in training load during the early-competition training phase can reduce the odds of injury without compromising agility performances in collision sport athletes. PMID- 17852697 TI - Hemispheric asymmetries in feature integration during visual word recognition. AB - Although the definitive source of the left hemisphere's superiority for visual word recognition remains illusive, some argue that the left (LH) and right (RH) hemispheres engage different strategies during early perceptual processes involved in stimulus encoding. In particular, it is proposed that the LH treats a word as a unitary perceptual group whereas the RH processes the letters comprising a word as a series of individual perceptual units. The present study investigated support for this processing distinction by examining hemispheric strategies for temporal integration using Prinzmetal and Millis-Wright's (1984) feature-binding paradigm. A total of 20 participants identified the colour and identity of a target letter, presented within a three-letter word (e.g., ART) or nonword (e.g., HRF), directed to their left or right visual field. Errors were classified on the basis of whether they involved substitution of a colour present within the stimulus but at a different location (ON error), or the substitution of a colour not present within the stimulus (OFF error). As anticipated, for word stimuli there was a higher proportion of OFF errors associated with trials directed to the RH, consistent with the notion that the LH treats words as single perceptual units and is hence biased toward miscombination of perceptual information present within the stimulus. The pattern of ON errors across stimulus type provided clear evidence of RH sequential encoding effects, with the number of errors increasing markedly across the ordinal position of the letters comprising the stimulus string. As such, these data provide new evidence that the LH's advantage for visual word recognition arises, at least in part, from the ability to encode verbal stimuli as single perceptual units. PMID- 17852698 TI - Laterality in coiling behaviour of snakes: another interpretation. AB - The direction of coiling was periodically recorded for two species of viperid snakes--copperheads (Agkistrodon contortrix) and cottonmouths (Agkistrodon piscivorus). Overall, neither species showed a significant preference for coiling in a particular direction. Only 1 of 22 snakes exhibited an individual preference, a result within expectation for random direction of coiling when using a 5% rejection level for statistical testing. A previously published claim for laterality in coiling direction by cottonmouths presented similar results but came to the opposite conclusion. The data from the combined studies suggest that if laterality in coiling direction does occur, it is extremely weak and inconsistent. PMID- 17852699 TI - Hippocampal asymmetry in serotonergic modulation of learning and memory in rats. AB - The modulation of learning and memory after left or right microinjections of the selective 5-HT1A receptor agonist 8-OH-DPAT and of the 5-HT1A receptor antagonist NAN190 into the hippocampal CA1 area of male Wistar rats was studied. Microinjections of 8-OH-DPAT (1 microg) into the right or left CA1 hippocampal area produced a significant decrease in the number of avoidances in a shuttle box. The impairing effect of 8-OH-DPAT was more pronounced when injected into the right hippocampus compared to the left one. Microinjections of NAN190 (1 microg) into the right or left CA1 hippocampal area produced a significant increase in the number of avoidances in a shuttle box. Right microinjections of NAN190 increased the number of avoidances more strongly than compared to left injections. These effects on learning and memory were more pronounced after injection of either of the serotonergic agents into the right CA1 hippocampal area compared to the left. The stronger memory-modulating effect after injection of 8-OH-DPAT or NAN190 into the right CA1 hippocampal area suggests a rightward bias in the rat. PMID- 17852700 TI - The influence of musical experience on lateralisation of auditory processing. AB - The influence of musical experience on free-recall dichotic listening to environmental sounds, two-tone sequences, and consonant-vowel (CV) syllables was investigated. A total of 60 healthy right-handed participants were divided into two groups according to their active musical competence ("musicians" and "non musicians"). In both groups, we found a left ear advantage (LEA) for nonverbal stimuli (environmental sounds and two-tone sequences) and a right ear advantage (REA) for CV syllables. Dichotic listening to environmental sounds was uninfluenced by musical experience. The total accuracy of recall for two-tone sequences was higher in musicians than in non-musicians but the lateralisation was similar in both groups. For CV syllables a lower REA was found in male but not female musicians in comparison to non-musicians. The results indicate a specific sex-dependent effect of musical experience on lateralisation of phonological auditory processing. PMID- 17852701 TI - Tests of the right shift genetic model for two new samples of family handedness and for the data of McKeever (2000). AB - Two new family samples are described for handedness in parents and children. In the first sample, drawn from the general population, questionnaires were completed for each individual (a self-report sample). In the second sample students completed a handedness questionnaire and described the handedness of their parents (indirect report sample). The percentages of left-handed children in the various family types (R x R, R x L etc., father x mother) were tested for goodness of fit to the predictions of the right shift genetic model, along with tests for the findings of McKeever (2000). Fits for the self-report sample were good for all family types. For the indirect report sample fits were good for many family types but there were more left-handed daughters than expected in R x L families and fewer than expected in L x R families. In the McKeever sample there was a shortfall of sons in L x R families but the fit for sons in R x L families was excellent. It is concluded that differences between samples here, and in the literature, are variable and probably due to sampling errors when the assessment of parental handedness depends on indirect report. Findings for sex differences do not suggest a need for hypotheses about X-linked mechanisms. PMID- 17852702 TI - Auditory priming of frequency and temporal information: effects of lateralised presentation. AB - Asymmetric distribution of function between the cerebral hemispheres has been widely investigated in the auditory modality. The current approach borrows heavily from visual local-global research in an attempt to determine whether, as in vision, local-global auditory processing is lateralised. In vision, lateralised local-global processing likely relies on spatial frequency information. Drawing analogies between visual spatial frequency and auditory dimensions, two sets of auditory stimuli were developed. In the high-low stimulus set we manipulate frequency information, and in the fast-slow stimulus set we manipulate temporal information. The fast-slow stimuli additionally mimic visual hierarchical stimulus structure, in which the arrangement of local patterns determines the global pattern. Unlike previous auditory stimuli, the current stimulus sets contain the experimental flexibility of visual local-global hierarchical stimuli allowing independent manipulation of structural levels. Previous findings of frequency and temporal range priming were replicated. Additionally, by presenting stimuli monaurally, we found that priming of frequency ranges (but not temporal ranges) was found to vary by ear, supporting the contention that the hemispheres asymmetrically retain traces of prior frequency processing. These results contribute to the extensive literature revealing cerebral asymmetries for the processing of frequency information, and extend those results to the realm of priming. PMID- 17852703 TI - Handedness in Great Britain. AB - Two large British databases of handedness assessed by writing hand at 10-11 years of age were analysed by geographical region. Left-handedness was found to vary significantly across regions according to one survey but not the other. In both data sets, left-handed writing was significantly more frequent in England than in Scotland and Wales combined. Possible reasons for this difference are discussed. PMID- 17852704 TI - Does Irish-dance training influence lower-limb asymmetry? AB - Irish-dance is a dance form where asymmetry is required. This study investigated the influence of Irish-dance training on four lower-limb asymmetries by comparing 100 Irish-dancers and 100 non-dancers. All four asymmetries showed significant differences between the dancers and the non-dancers: the rigidity of the dance training influencing those asymmetries. PMID- 17852705 TI - Failure to find asymmetry in auditory gap detection. AB - Several previous studies have demonstrated a right ear advantage in the detection of a brief silent gap in a broadband noise, with one study indicating that such an asymmetry does not exist. If such an asymmetry reflects more efficient temporal processing of auditory stimuli in the left hemisphere of the brain, then an asymmetry may be expected to exist regardless of the experimental procedure. Three sequential studies are summarised that use both adaptive threshold measurements and yes/no procedures to assess auditory gap detection performance both with and without the presence of a dichotic masker. These studies fail to reveal any systematic bias in performance towards one ear, and it is suggested that the right ear advantage demonstrated in previous studies may not reflect auditory gap detection performance per se, but may reflect the participants' response bias in the particular type of tasks used. PMID- 17852706 TI - Spinal epidural lipomatosis in myeloma. PMID- 17852707 TI - Promoter hypermethylation of multiple genes in gastric lymphoma. AB - Aberrant hypermethylation of CpG islands in the promoter region of tumor suppressor and other important genes in neoplastic cells of lymphoma has been demonstrated to be one of the mechanisms for epigenetic loss of gene function. In this study, we analyzed promoter hypermethylation of the following genes in 49 cases of primary gastric lymphoma (PGL): ATM, p16INK4a(CDKN2A), hMLH1, MGMT, DAPK, and CDH1(ECAD). The PGL cases studied included 26 (53%) cases of diffuse large B-cell lymphoma (DLBCL), 12 (25%) cases of extranodal marginal zone lymphoma (MZL), 7 (14%) cases of MZL with large cell transformation (MZL/DLBCL), 1 (2%) case of follicular lymphoma (FL), one (2%) case of Burkitt-like lymphoma (BL), one case (2%) of lymphoplasmacytic lymphoma (LPL) and one case (2%) of peripheral T-cell lymphoma. Available pathologic data regarding to extragastric involvement at the time of resection of the PGLs were reviewed and correlated. Promoter hypermethylation was detected in 6 of 49 (12.2%) cases for ATM; 13 of 49 (26.5%) for p16INK4a, 19 of 49 (38.8%) for hMLH1; 22 of 49 (44.9%) for MGMT; 27 of 49 (55.1%) for DAPK and 16 of 49 (32.7%) for CDH1. A total of 85% of the PGLs had promoter hypermethylation in at least one of these genes. With different histologic subtypes, promoter hypermethylation of DAPK, hMLH1, and CDH1 genes occurred in 70%, 42%, and 42% respectively for DLBCL, which appeared to be higher than combined MZL and MZL/DLBCL subgroup. Approximately 81% PGLs demonstrated H. pylori infection by immunohistochemistry. H. pylori status did not appear to be statistically correlated with promoter hypermethylation of the genes. Of 37 PGL cases, 19 cases had extragastric involvement at the time of resection, indicating relatively higher stage disease. The frequencies of promoter methylation in those cases were 58% for DAPK, 42% for hMLH1, 37% for CDH1, 26% for p16INK4a and 11% for ATM respectively. The promoter methylation at MGMT gene was significantly higher in the PGLs without extragastric involvement (61%) as compared to those with extragastric involvement (26%). PMID- 17852709 TI - Primary testicular precursor B-lymphoblastic lymphoma: a rare entity. PMID- 17852708 TI - Higher rates of t(11;18) in Chinese patients with transformed type of MALT lymphoma suggest novel pathways for progression of the disease. AB - To detect the t(11;18) chromosome translocation in different stages of mucosa associated lymphoid tissue (MALT) lymphoma, we established a RT-PCR method by adopting three new primer pairs and using the RNA extracted from the paraffin tissues to amplify the t(11;18) fusion gene API2-MALT1 in shorter lengths. Our results showed five key findings, which are (a) higher detection rates of t(11;18) (21.13%) in Chinese patients with transformed MALT lymphoma, (b) lower detection rates of t(11;18) in stomach MALT lymphoma, (c) different organ localizations of MALT lymphoma in Chinese patients, (d) higher nuclear expression rates of Bcl-10 in low grade MALT (51.72%), and (e) lower response rates (50% CR, and 50% PR) to anti-H.-pylori therapy. These findings suggest novel pathways for low-grade MALT lymphoma to be progressed into transformed MALT lymphoma. This study also suggests that amplification of shorter length of PCR products from the paraffin-fixed tissues increases sensitivity, which is significant in improving the selection of the therapeutic regimen and assessing the prognosis of the disease. PMID- 17852710 TI - Clofarabine: past, present, and future. AB - Clofarabine is a good generation purine nucleoside analogue designed to overcome the limitations and to incorporate the best qualities of both cladribine and fludarabine. Clofarabine is thought to work via three mechanisms: inhibition of ribonucleotide reductase; incorporation to DNA; and induction of apoptosis. Given these mechanism of action, clofarabine would be predicted to act synergistically with other chemotherapeutic agents such as other purine nucleoside analogues and DNA damaging or cross linking agents such as anthracyclines and platinum-based compounds. Intravenous clofarabine showed significant efficacy in pediatric leukemias (specifically, acute lymphoblastic leukemia (ALL)) and, in 2004, it was approved by the United States Food and Drug Administration (FDA) for the treatment of pediatric relapsed/refractory ALL after at least two regimens. In adults, clofarabine has shown significant efficacy in hematologic malignancies including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) alone and in combinations. Ongoing and future studies will examine the use of clofarabine in elderly patients with AML for whom standard regimens are too toxic, and in MDS intravenous and oral forms of the drug. PMID- 17852711 TI - Pulmonary hypertension in patients with essential thrombocythemia and reactive thrombocytosis. AB - Increased incidence of pulmonary hypertension (PH) has been reported in patients with chronic myeloproliferative disorders. The exact incidence of PH in essential thrombocythemia (ET) is unknown. Most of the reported literature consists of case reports or small studies. We designed this study to asses the incidence of PH in patients with ET and reactive thrombocytosis. Previously or newly diagnosed 46 patients with ET, and 40 patients with reactive thrombocytosis secondary to iron deficiency anemia were found to be eligible for this study. Diagnosis of PH was established via transthoracic echocardiography. PH was found in 22 (47.8%) out of 46 patients with ET. Seven patients with PH were newly diagnosed ET, 5 patients with PH were in low, and the other patients with PH were in intermediate or high risk category. We found statistically significant difference in terms of platelet counts between ET patients with PH and without PH (p = 0.027). None of the patients with reactive thrombocytosis had PH. In conclusion, PH appears to be common in patients with ET. Therefore, all patients with ET should be evaluated for PH. Larger and prospective studies are required to clarify the long-term impact of PH on the survival of these patients. Future studies are also needed to determine whether cytoreductive treatment and aspirin prevent the development of PH, and to determine the effects of cytoreductive treatments and aspirin on the prognosis of PH. The effect of PH on ET prognosis should also be determined in low risk ET patients. PMID- 17852713 TI - Hearing and phonetic criteria in voice measurement: clinical applications. AB - Quantitative clinical voice analysis is discussed with special reference to four factors: 1) measurement criteria that are based on well established auditory parameters; 2) voice material that is modelled on the connected speech of ordinary spoken communication rather than sustained vowels; 3) direct monitoring so as to provide both acoustic and vocal fold contact signals; and 4) phonetic structural similarities across what are ordinarily regarded as highly dissimilar languages. These factors have motivated the development and clinical application of physical analyses that provide measurements related both to vocal fold function and to the perceptual attributes of pitch, loudness, and an important aspect of voice quality. PMID- 17852714 TI - The relative effectiveness of vocal hygiene training and vocal function exercises in preventing voice disorders in primary school teachers. AB - Voice disorders in teachers have a significant impact on their occupational functioning and well being. Teachers are believed to have a high prevalence of voice problems because of the unfavourable acoustic environments in which they work and the high vocal demands and stress levels associated with teaching. Although the types of voice problems teachers experience should be preventable because they are caused by factors that teachers can change, there is limited information available regarding the effectiveness of different preventative strategies. Therefore, the aim of this study was to investigate the effectiveness of vocal hygiene training (VH) and vocal function exercises (VFE) in reducing vocal symptoms and vocal misuse, and increasing knowledge of voice care, maximum phonation time, and maximum phonational frequency range in school teachers. Thirty-seven teachers from four schools in Melbourne, Australia, participated in the study. Schools were randomly allocated to one of three groups: VH, VFE, and no-treatment control. The VH and VFE participants reported improved vocal characteristics and voice knowledge after training while the control group showed deterioration on most variables. The VH participants showed greater improvements than the VFE participants. These fundings indicate that preventative voice training for teachers is likely to be effective. PMID- 17852715 TI - The resonance tube method in voice therapy: description and practical implementations. AB - Phonation into glass tubes, keeping the free end of the tube in water, has been a frequently used voice therapy method in Finland for more than four decades. These so-called resonance tubes, introduced by Professor Sovijarvi in the 1960s, are used in different ways depending on the patient's diagnosis and the goal of the voice therapy. In this paper, some of the most common ways of using the tube are presented. PMID- 17852716 TI - Successfully treated Candida krusei infection of the lumbar spine with combined caspofungin/posaconazole therapy. AB - Candidal vertebral osteomyelitis represents an extremely rare invasive mycosis and can be difficult to treat due to poor drug penetration into bony tissue. We report on a case of vertebral osteomyelitis caused by Candida krusei in a patient who had neutropenia as a result of chemotherapy for acute myelogenous leukaemia. The patient received prophylactic liposomal amphotericin B during chemotherapy but became febrile and experienced severe lumbar pain. Magnetic resonance imaging revealed vertebral osteochondrosis. C. krusei was recovered from blood cultures and voriconazole monotherapy was initiated but proved unsuccessful. The patient was then started on caspofungin monotherapy, which was discontinued after Candida krusei was no longer recoverable from blood cultures. However, as lumbar pain increased and spinal biopsy confirmed the presence of Candida krusei, caspofungin therapy was resumed. Oral posaconazole was added to the regimen when the patient did not improve after 30 days of caspofungin therapy. Combined antimycotic therapy resulted in a successful outcome. PMID- 17852718 TI - Chronic mucocutaneous candidiasis and oesophageal cancer. AB - Chronic mucocutaneous candidiasis (CMC) is often accompanied by endocrine or inflammatory disorders. The association of CMC with squamous cell carcinoma of the oral cavity or oesophagus have been described in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). We describe three cases of CMC and oesophageal cancer without the APECED syndrome. The first case refers to a 41-year-old man with Candida paronychia and oral infection and selective IgA deficiency since childhood, who later developed an oesophageal cancer. The second case is a 30-year-old man who presented CMC features at the age of 2 together with selective IgA deficiency. Later on he was diagnosed with an oesophageal squamous cell carcinoma. His mother, the third case reported, had oral thrush since childhood and at the age of 29 she presented with an oesophageal squamous cell carcinoma. The three patients reported died due to oesophageal cancer. This is the first case report describing the development of oesophageal cancer in patients with CMC without the APECED syndrome. Patients with CMC need close follow-up with good oral hygiene and aggressive treatment of oral and oesophageal candidiasis. Routine endoscopic screening for patients with CMC that develop symptoms of oesophageal candidiasis and for patients with CMC with a family history of oesophageal cancer is suggested. Avoidance of additional risk factors for oral and oesophageal cancer like cigarette smoking and excessive alcohol consumption are also warranted. PMID- 17852717 TI - Discovering the secrets of the Candida albicans agglutinin-like sequence (ALS) gene family--a sticky pursuit. AB - The agglutinin-like sequence (ALS) family of Candida albicans includes eight genes that encode large cell-surface glycoproteins. The high degree of sequence relatedness between the ALS genes and the tremendous allelic variability often present in the same C. albicans strain complicated definition and characterization of the gene family. The main hypothesis driving ALS family research is that the genes encode adhesins, primarily involved in host-pathogen interactions. Although adhesive function has been demonstrated for several Als proteins, the challenge of studying putative adhesins in a highly adhesive organism like C. albicans has led to varying ideas about how best to pursue such investigations, and results that are sometimes contradictory. Recent analysis of alsdelta/alsdelta strains suggested roles for Als proteins outside of adhesion to host surfaces, and a broader scope of Als protein function than commonly believed. The availability and use of experimental methodologies to study C. albicans at the genomic level, and the ALS family en masse, have advanced knowledge of these genes and emphasized their importance in C. albicans biology and pathogenesis. PMID- 17852720 TI - Promoting self-awareness and reflection through an experiential mind-body skills course for first year medical students. AB - BACKGROUND: This research examines student evaluations of their experience and attitudes in an 11 week mind-body skills course for first year medical students. AIMS: The aim is to understand the impact of this course on students' self awareness, self-reflection, and self-care as part of their medical education experience. METHODS: This study uses a qualitative content analysis approach to data analysis. The data are 492 verbatim responses from 82 students to six open ended questions about the students' experiences and attitudes after a mind-body skills course. These questions queried students' attitudes about mind-body medicine, complementary medicine, and their future as physicians using these approaches. RESULTS: The data revealed five central themes in students' responses: connections, self discovery, stress relief, learning, and medical education. CONCLUSIONS: Mind-body skills groups represent an experiential approach to teaching mind-body techniques that can enable students to achieve self-awareness and self-reflection in order to engage in self-care and to gain exposure to mind-body medicine while in medical school. PMID- 17852721 TI - Linking thought suppression and recovered memories of childhood sexual abuse. AB - There are two types of recovered memories: those that gradually return in recovered memory therapy and those that are spontaneously recovered outside the context of therapy. In the current study, we employed a thought suppression paradigm, with autobiographical experiences as target thoughts, to test whether individuals reporting spontaneously recovered memories of childhood sexual abuse (CSA) are more adept at suppressing positive and anxious autobiographical thoughts, relative to individuals reporting CSA memories recovered in therapy, relative to individuals with continuous abuse memories, and relative to controls reporting no history of abuse. Results showed that people reporting spontaneously recovered memories are superior in suppressing anxious autobiographical thoughts, both in the short term and long term (7 days). Our findings may partly explain why people with spontaneous CSA memories have the subjective impression that they have "repressed" their CSA memories for many years. PMID- 17852722 TI - Short report: the effect of expertise in hiking on recognition memory for mountain scenes. AB - The nature of an expert memory advantage that does not depend on stimulus structure or chunking was examined, using more ecologically valid stimuli in the context of a more natural activity than previously studied domains. Do expert hikers and novice hikers see and remember mountain scenes differently? In the present experiment, 18 novice hikers and 17 expert hikers were presented with 60 photographs of scenes from hiking trails. These scenes differed in the degree of functional aspects that implied some action possibilities or dangers. The recognition test revealed that the memory performance of experts was significantly superior to that of novices for scenes with highly functional aspects. The memory performance for the scenes with few functional aspects did not differ between novices and experts. These results suggest that experts pay more attention to, and thus remember better, scenes with functional meanings than do novices. PMID- 17852723 TI - Temporal distribution of favourite books, movies, and records: differential encoding and re-sampling. AB - The reminiscence bump is the effect that people recall more personal events from early adulthood than from childhood or adulthood. The bump has been examined extensively. However, the question of whether the bump is caused by differential encoding or re-sampling is still unanswered. To examine this issue, participants were asked to name their three favourite books, movies, and records. Furthermore,they were asked when they first encountered them. We compared the temporal distributions and found that they all showed recency effects and reminiscence bumps. The distribution of favourite books had the largest recency effect and the distribution of favourite records had the largest reminiscence bump. We can explain these results by the difference in rehearsal. Books are read two or three times, movies are watched more frequently, whereas records are listened to numerous times. The results suggest that differential encoding initially causes the reminiscence bump and that re-sampling increases the bump further. PMID- 17852724 TI - Situation models and memory: the effects of temporal and causal information on recall sequence. AB - Participants watched an episode of the television show Cheers on video and then reported free recall. Recall sequence followed the sequence of events in the story; if one concept was observed immediately after another, it was recalled immediately after it. We also made a causal network of the show's story and found that recall sequence followed causal links; effects were recalled immediately after their causes. Recall sequence was more likely to follow causal links than temporal sequence, and most likely to follow causal links that were temporally sequential. Results were similar at 10-minute and 1-week delayed recall. This is the most direct and detailed evidence reported on sequential effects in recall. The causal network also predicted probability of recall; concepts with more links and concepts on the main causal chain were most likely to be recalled. This extends the causal network model to more complex materials than previous research. PMID- 17852725 TI - The impact of eyewitness identifications from simultaneous and sequential lineups. AB - Recent guidelines in the US allow either simultaneous or sequential lineups to be used for eyewitness identification. This paper investigates how potential jurors weight the probative value of the different outcomes from both of these types of lineups. Participants (n=340) were given a description of a case that included some exonerating and some incriminating evidence. There was either a simultaneous or a sequential lineup. Depending on the condition, an eyewitness chose the suspect, chose a filler, or made no identification. The participant had to judge the guilt of the suspect and decide whether to render a guilty verdict. For both simultaneous and sequential lineups an identification had a large effect,increasing the probability of a guilty verdict. There were no reliable effects detected between making no identification and identifying a filler. The effect sizes were similar for simultaneous and sequential lineups. These findings are important for judges and other legal professionals to know for trials involving lineup identifications. PMID- 17852726 TI - Are memories for sexually traumatic events "special"? A within-subjects investigation of trauma and memory in a clinical sample. AB - According to a long-standing clinical tradition, sexually traumatic experiences are processed and recalled differently from other experiences, often leading to memory impairment. In this study, we compared the characteristics of traumatic memories for sexual violence and two other types of emotional experiences. N=44 women recruited from a local sexual trauma agency were asked to recall and describe three autobiographical events: sexual abuse/assault, a non-sexual trauma, and a positive emotional event. The characteristics of the three memory types were compared on both subjective and objective measures. Further, the potential influences of level of traumatic impact and dissociation were assessed. Results indicated that memories for sexual trauma were not impaired or fragmented relative to other memories. Instead, memories for sexual trauma were associated with a remarkably high level of vividness, detail, and sensory components. Further, high levels of traumatic impact were not associated with memory impairment. Implications for the ongoing traumatic memory debate are discussed. PMID- 17852727 TI - Trauma and memory: effects of post-event misinformation, retrieval order, and retention interval. AB - The present study concerned effects of misinformation, retrieval order, and retention interval on eyewitness memory for a traumatic event (a vivid murder). Relations between misinformation acceptance and compliance were also examined. The classic three-stage misinformation paradigm (Loftus, 1979) was employed, with a multi-component recognition test added. Either immediately or 2 weeks after viewing a distressing film, 232 adults read a narrative (misleading or control) about the murder and then took a recognition test that tapped memory for central and peripheral details. Test-item order either matched the chronology of the film or was randomly determined. Significant misinformation effects were obtained. Moreover, control participants were more accurate in response to questions about central than peripheral information; however, this was not so for misinformed participants. Sequential but not random retrieval order resulted in a higher proportion of correct responses for central as opposed to peripheral misinformation questions. Compliance was significantly related to misinformation effects. Delay increased participants' suggestibility, impaired memory accuracy, and produced higher confidence ratings for misinformed participants compared to controls. Findings indicate that even for a highly negative event, adults' memory is not immune to inaccuracies and suggestive influences. PMID- 17852728 TI - The effect of emotional stress on involuntary and voluntary conscious memories. AB - Clinical theories of post-traumatic stress disorder often claim that intrusive (involuntary) memories favour emotionally stressful material and that these memories come with more sensory imagery and emotional reliving compared to voluntary memories. However, these assumptions have not been verified experimentally. Here we obtained recordings of emotional reactions to aversive pictures at the time of encoding, as well as records of involuntary and voluntary memories of these pictures in a subsequent diary study. A comparison of individual ratings, obtained during encoding, of pictures recalled involuntarily and voluntarily showed that emotional stress at encoding increased overall accessibility, independent of whether recall was voluntary or involuntary. However at the time of recall, voluntary memories scored higher on narrative content and on measures of imagery. The findings are compatible with research on emotion and memory in general, but challenge clinical claims of differential involuntary versus voluntary access to emotionally stressful events. PMID- 17852729 TI - Memory consistency for traumatic events in Dutch soldiers deployed to Iraq. AB - Retrospective accounts of traumatic events are consistently associated with symptoms of post-traumatic stress disorder (PTSD). This has often been interpreted as causal impact of such events on psychological functioning, but recent studies suggest that the causal direction is (partly) reversed: high levels of PTSD symptoms may be associated with amplified recollections of precipitating traumatic events. The aim of this prospective study was to index the consistency with which Dutch Army soldiers reported traumatic stressors and nontraumatic stressors on their deployment to Iraq, and to examine to what extent PTSD symptoms and pre-existing reporting biases, such as that arising from neuroticism, affect memory inconsistency. Retrospective accounts of stressors were highly variable over time. Individuals with higher levels of PTSD symptoms and neuroticism, lower levels of extraversion, and fewer prior missions, were more prone to increased reporting over time. PMID- 17852730 TI - The effects of local and global processing orientation on eyewitness identification performance. AB - Recent work has demonstrated that performance on a simultaneous target-present photographic line-up can be enhanced by prior global processing orientation, and hindered by prior local processing orientation induced by processing Navon letter stimuli. A series of studies explore the generality of this processing bias effect using either videotaped scenarios or live interactions. Five experiments demonstrate that these effects are seen across a range of test stimuli, test formats, and test instructions. These data inform the processes engaged in by witnesses when making line-up identifications and indicate that it may be possible to improve the accuracy of witnesses making such judgements. PMID- 17852731 TI - A novel therapeutic approach to non-parasitic splenic cysts: laparoscopic fenestration and endothelium obliteration. AB - Splenic cyst is a relatively rare disease; true splenic cysts are classified as parasitic and non-parasitic cysts. Although most cysts are asymptomatic, large cyst cases show clinical symptoms, consisting mainly of dyspepsia and fullness in the upper left abdomen. Surgical intervention is recommended primarily for large cysts to prevent complications such as rupture, hemorrhage, and infection. This paper presents our experience of eleven laparoscopic procedures for non-parasitic splenic cysts. Laparoscopic fenestration was performed in all cases, and the cyst endothelium was destroyed . All operations were accomplished successfully. The mean operative time was 56 minutes (range 40-90 minutes). Intraoperative bleeding was 15 ml (range 5-30 ml), oral food intake was started on the first postoperative day. The median duration of postoperative hospitalization was 2.8 days (range 1-7 days). There were no postoperative complications. All cases were followed up for a period of 21 months to 5.5 years, and no recurrence occurred. Laparoscopic fenestration and endothelium obliteration is an advantageous approach to large non-parasitic splenic cysts with little postoperative pain, fast recovery, splenic tissue and splenism preservation, low complication rates, and a short hospital stay; it is easily accepted by patients. It yields favorable medium-term results. Our study confirms that good results can be achieved with an approach of laparoscopic fenestration and endothelium obliteration for simple non parasitic splenic cysts. PMID- 17852732 TI - Minimally invasive vertebroplasty managed by a two C-arm fluoroscopic technique. AB - One C-arm fluoroscope is widely considered to be sufficient for effectively monitoring minimally invasive vertebroplasty. However, rotating the C-arm fluoroscope for different radiographic views of the spine can be time-consuming, causing delay in detecting cement leakage. We retrospectively reviewed the results of minimally invasive vertebroplasty utilizing two C-arm fluoroscopes in the treatment of osteoporotic vertebral fractures. Forty-two patients (50 vertebrae) were treated with minimally invasive vertebroplasty under the guidance of two C-arm fluoroscopes. The mean operation time, patient satisfaction rate and the incidences of cement leakage or infection were used to evaluate the feasibility and efficacy of the two C-arm fluoroscopic technique in performing minimally invasive vertebroplasty. The mean follow-up duration was 17.4 months (range 6 approximately 36). The mean operation time was 37+/-14 minutes. Thirty patients (71%) were very satisfied or satisfied with the procedure. Cement leakages were identified in nine patients (nine vertebrae, 18%). Only one vertebra had a posterior leakage into spinal canal, which did not cause neurologic deficits. No wound infection was observed. This study indicates that the two C-arm fluoroscopic technique provides simultaneous antero-posterior and lateral radiographic views, and therefore may reduce the operation time. No symptomatic cement leakage or wound infection was noted in this investigation. Moreover, no additional staff is needed to rotate the C-arm for fluoroscopy. The proposed technique has been shown to be effective and useful for performing minimally invasive vertebroplasty. PMID- 17852733 TI - Endoscope-assisted supraorbital keyhole approach for the resection of benign tumors of the sellar region. AB - The objective of the study was to evaluate the effectiveness of the supraorbital "keyhole" approach with endoscope assistance in surgical treatment of benign tumors around the sellar region. Thirty-five patients, including 19 pituitary tumors, 11 craniopharyngiomas and five tuberculum sellae meningiomas, were enrolled in this study. The tumors were resected through an endoscope-assisted supraorbital keyhole approach via a small skin incision within the eyebrow. Complete removal of the sellar region tumors was achieved in all 35 cases by endoscope-assisted supraorbital keyhole approach. Mean length of hospital stay after surgery was 10.2 days (range 5 - 17). There was no patient with evidence of residual or recurrent tumor during the follow-up period. There was no infection, bleeding, further vision impairment, oculomotor nerve injury or other cranial nerve injury symptom owing to surgery. Though some patients suffered from insipidus, hyperprolactinemia, subcutaneous edema or other postoperative complications, they eventually recovered with or without drug administration. The supraorbital "keyhole" approach with endoscopic assistance in the surgical treatment of benign tumors around the sellar region is an ideal pattern. PMID- 17852734 TI - Syntaxin 16 is enriched in neuronal dendrites and may have a role in neurite outgrowth. AB - Polarized membrane traffic to different domains of the neuron is well documented, and is required for both establishment and maintenance of neuronal polarity. Some soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins, particularly syntaxin 12/13 and TI-VAMP/VAMP7, have known roles in the neuron. We report here that the brain-enriched SNARE syntaxin 16 (Syn 16) is specifically enriched in neuronal dendrites and found at Golgi outposts, thus confirming that Golgi outposts are endowed with a trans-Golgi network (TGN) component. Over-expression of wild type syntaxin 16 moderately stimulates, whereas that of an N-terminal deletion mutant (Syn 16-DeltaNt) inhibits, neurite outgrowth in both mouse Neuro-2a cells and primary cortical neurons. Consistent with an inhibited neurite growth, cells over-expressing Syn 16-DeltaNt have diminished betaIII-tubulin and F-actin labeling. RNA interference-mediated silencing of syntaxin 16 in primary cortical neurons significantly retards neurite outgrowth. Syntaxin 16 may thus play a role in neurite outgrowth and perhaps other specific dendritic anterograde/retrograde traffic. PMID- 17852735 TI - Effects of 2-hydroxyoleic acid on the structural properties of biological and model plasma membranes. AB - Genetic hypertension is associated with alterations in lipid metabolism, membrane lipid composition and membrane-protein function. 2-Hydroxyoleic acid (2OHOA) is a new antihypertensive molecule that regulates the structure of model membranes and their interaction with certain peripheral signalling proteins in vitro. While the effect of 2OHOA on elevated blood pressure is thought to arise through its influence on signalling proteins, its effects on membrane lipid composition remain to be assessed. 2OHOA administration altered the lipid membrane composition of hypertensive and normotensive rat plasma membranes, and increased the fluidity of reconstituted liver membranes from hypertensive rats. In spontaneously hypertensive rats (SHR), treatment with 2OHOA increased the cholesterol and sphingomyelin content while decreasing that of phosphatidylserine phosphatidylinositol lipids. In addition, monounsaturated fatty acid levels increased as well as the propensity of reconstituted membranes to form HII phases. These data suggest that 2OHOA regulates lipid metabolism that is altered in hypertensive animals, and that it affects the structural properties of liver plasma membranes in SHR. These changes in the structural properties of the plasma membrane may modulate the activity of signalling proteins that associate with the cell membrane such as the Galphaq/11 protein and hence, signal transduction. PMID- 17852736 TI - Sesquineolignans from the flowers of Centaurea furfuracea Coss. et Dur. (Asteraceae). AB - Two new sesquineolignans, Furfuraceol A (1) and Furfuraceol B (2), have been isolated from the flowers of Centaurea furfuracea as a mixture of two isomers. Their structures have been determined by spectroscopic methods including 2D NMR spectroscopy COSY, HMQC, HMBC and NOESY. PMID- 17852737 TI - Antinociceptive and anthelmintic activity of Canna indica. AB - Dried, coarsely powdered leaves, flowers, rhizomes and seeds of Canna indica were successively extracted with benzene and methanol in Soxhlet apparatus. The effect of benzene and methanol extracts of various parts of C. indica on nociceptive response using writhing test and hot plate method in mice was examined. All the extracts of C. indica showed significant central and peripheral analgesic activity in hot plate method and acetic acid-induced writhing test, respectively, at the dose of 50 mg kg(-1) intraperitoneally. Methanolic extract of leaves of C. indica showed highest increase in reaction time in hot plate method while benzene extract of leaves of C. indica showed more inhibitory effect on writhing induced by acetic acid. Anthelmintic activity of these extracts was evaluated on Pheritima posthuma. Results showed that the methanolic extract of rhizomes of the plant took less time to cause paralysis of the earthworms. PMID- 17852738 TI - Diterpenoid alkaloids from Delphinium gracile. AB - Two highly oxygenated hetisine-type diterpenoid alkaloids, delphigraciline (1), 14-hydroxyhetisinone N-oxide (2), and the norditerpenoid alkaloid 8 methoxykarakoline (3), were isolated from a neutral extract of Delphinium gracile. Their structures were elucidated on the basis of spectroscopic data and by comparison with previously reported spectroscopic data of similar alkaloids. Their antiparasitic and insecticidal activities are also discussed. PMID- 17852739 TI - A new isocoumarin from Hypericum annulatum. AB - A new isocoumarin, annulatomarin (1), together with the known physcion and beta sitosterol were isolated from the aerial parts of Hypericum annulatum. The structure of the new compound was established as 6,8-dihydroxy-7-methoxy-3-phenyl 3,4-dihydro-1H-isochromen-1-one on the basis of detailed spectroscopic analysis. Annulatomarin exhibited a modest growth-inhibitory activity in vitro against human chronic myeloid leukaemia LAMA-84 cells with an IC(50) = 111 microM. PMID- 17852740 TI - Endemic species of sardo-corso-balearic area: molecular composition and biological assay of Teucrium. AB - Teucrium marum and T. subspinosum have been extracted with different polarity solvents, each crude extract was analysed with (1)H-NMR to compare the overall metabolic component. The polar extracts showed antioxidant activity in vitro. Verbascoside and arabinosyl-verbascoside were isolated and identified. Their concentrations were in connection to the antioxidant activity. PMID- 17852741 TI - New xenicanes from Xenia viridis. AB - The dichloromethane extract of Xenia viridis afforded two new xenicane diterpenoids (3 and 4) by silica gel chromatography. The oxirane ring of 3 was found to be susceptible to a slow ring opening under acidic conditions to afford 5. Their structures were elucidated by extensive 1D and 2D NMR spectroscopy. PMID- 17852742 TI - Identification and characterization of phenolic compounds in castor seed. AB - Phenolic compounds, polyphenols, and flavonoids occur ubiquitously in plant kingdom, because they are important in plants for normal growth development and defense against infection and injury. Currently, there are no reports available on the phenolic compounds obtained from the residues of the oil-extracting process from defatted castor seed powder. Our studies, for the first time, in methanol-ether extract showed five low-molecular weight phenolic compounds namely p-coumaric acid, ferulic acid, o-coumaric acids, syringic, and cinnamic acids, which were in the soluble ether fractions. All these compounds showed strong absorbance at 240 nm. PMID- 17852743 TI - Iridoids from Gardenia jasminoides. AB - The dichloromethane extract of the air-dried flowers of Gardenia jasminoides Ellis. afforded a new iridoid natural product (1), and a diastereomeric mixture of two new iridoids (2a and 2b) in a 2 : 1 ratio. Their structures were elucidated by extensive 1D and 2D NMR spectroscopy. Antimicrobial tests on 1 indicated that it was moderately active against Candida albicans; slightly active against E. coli, Pseudomonas aeruginosa, Staphylococcus. aureus, and Trichophyton mentagrophytes; and inactive against Bacillus subtilis and Aspergillus niger. PMID- 17852744 TI - 11,20-Epoxybriaranes from the gorgonian coral Ellisella robusta (Ellisellidae). AB - Chemical investigation on the organic extract of the gorgonian coral Ellisella robusta furnished two 11,20-epoxybriaranes 1 and 2. The structures of briaranes 1 and 2 were assigned on the basis of spectroscopic evidence. The natural products of this type (11,20-epoxybriarane) were found to be a chemical marker for the gorgonian corals belonging to the family Ellisellidae. PMID- 17852745 TI - Microwave-assisted rapid extraction of red dye from Caesalpinia sappan heartwood. AB - Since ancient times Caesalpinia sappan heartwood dye has been well-known for its medicinal and dyeing properties. Isolation of the red dye using both conventional and newly developed microwave method was carried out. The conventional heating of 2 h provided 0.656 +/- 0.049 g of the dye and by microwave heating at 540 W for 20 min, the yield obtained was 0.747 +/- 0.047 g. Both the dyes were found to be the same as evidenced by UV, TLC and HPTLC studies. Antioxidant activity of the dyes was also carried out using DPPH and nitric oxide methods to confirm the similarity in their biological activity. The procedure developed can be used for the fast extraction of the red dye of C. sappan without affecting the nature of the product. PMID- 17852746 TI - Easy DNA extraction for rapid detection of Panax ginseng C. A. Meyer in commercial ginseng products. AB - An investigation was carried out in order to obtain an easy and rapid detection of Panax ginseng in commercial herbal products by using molecular techniques (polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP)). Two protocols and one commercial kit for DNA extraction were used. Four forms of commercial products were considered, i.e., dried body roots, dried root tails, dried root prongs and dried extracts. The RFLP of DNA amplified products by 18df/28ccr primers, obtained using Inf I, Sau 3A1 and Taq I endonucleases, allowed the identification of P. ginseng and its differentiation from P. quinquefolium. The presence of adulterants, as Mirabilis jalapa L. and Phytolacca acinosa Roxb. was excluded in the examined commercial samples. P. ginseng was detected in 63% of the considered samples according to the declaration of the labels, whereas negative results were obtained with the dried extract form. Therefore, the Invitrogen DNA extraction kit let the easy extraction of useful amounts of DNA and a standardisation of routine work, in comparison with the other molecular protocols so far used. PMID- 17852747 TI - In vitro anti-inflammatory activity of 4-arylcoumarins from endophytic Streptomyces aureofaciens CMUAc130 in murine macrophage RAW 264.7 cells. AB - This research was undertaken to find the in vitro inflammatory action of 5,7 dimethoxy-4-p-methoxylphenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin produced by Streptomyces aureofaciens CMUAc130. We investigated the effects of 5,7 dimethoxy-4-p-methoxylphenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin not only on the formation of nitric oxide (NO), PGE(2), TNF-alpha, IL-6 and IL-1beta, but also on inducible NO synthase and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced murine macrophage RAW 264.7 cells. The data obtained were consistent with the modulation of iNOS enzyme expression. A similar fashion was also observed when LPS-induced PGE(2) release and COX-2 expression were tested. The significant inhibitory effects were shown in concentration-dependent manners. In addition, 5,7-dimethoxy-4-p-methoxylphenylcoumarin and 5,7-dimethoxy-4 phenylcoumarin also mildly but significantly reduced the formation of TNF-alpha. These findings support the application of 5,7-dimethoxy-4-p methoxylphenylcoumarin and 5,7-dimethoxy-4-phenylcoumarin as anti-inflammatory agents. PMID- 17852748 TI - Xylopyrine-A and xylopyrine-B, two new peptide alkaloids from Zizyphus xylopyra. AB - Two new 13-membered cyclopeptide alkaloids, xylopyrine-A and xylopyrine-B have been isolated from Zizyphus xylopyra, and their structures established by spectral and chemical evidences. PMID- 17852749 TI - Antioxidant activity and total phenolic content of aqueous and methanolic extracts of Jordanian plants: an ICBG project. AB - As part of an International Cooperative Biodiversity Groups (ICBG) program to study Jordan's biodiversity, the relative levels of antioxidant activity and the total phenolic content of aqueous and methanolic extracts of a total of 95 plant species, all of Jordanian origin and those collected at random, have been measured. The total phenolic content of aqueous and methanolic extracts of the investigated plant species ranged from 4.4 to 78.3 mg and from 2.1 to 52.8 mg gallic acid equivalents g(-1) dry weight, respectively, while the total antioxidant capacity ranged from 20.0 to 916.7 and from 15.1 to 915.6 micromol Trolox equivalents g(-1) dry weight, respectively. Based on this collection, approximately 5% of assayed plants showed high levels of antioxidant activity. There was a significant linear correlation between antioxidant activity and total phenolic content for aqueous and methanolic extracts, suggesting that phenolic compounds were the predominant antioxidant components in the investigated plant species. Interestingly, a few of the collected plants had high-antioxidant activity yet "low" phenolic content includes Ceratonia siliqua and Viscum cruciatum. These plants may serve as sources of antioxidants with new chemotypes. PMID- 17852750 TI - Estimating sparse spectro-temporal receptive fields with natural stimuli. AB - Several algorithms have been proposed to characterize the spectro-temporal tuning properties of auditory neurons during the presentation of natural stimuli. Algorithms designed to work at realistic signal-to-noise levels must make some prior assumptions about tuning in order to produce accurate fits, and these priors can introduce bias into estimates of tuning. We compare a new, computationally efficient algorithm for estimating tuning properties, boosting, to a more commonly used algorithm, normalized reverse correlation. These algorithms employ the same functional model and cost function, differing only in their priors. We use both algorithms to estimate spectro-temporal tuning properties of neurons in primary auditory cortex during the presentation of continuous human speech. Models estimated using either algorithm, have similar predictive power, although fits by boosting are slightly more accurate. More strikingly, neurons characterized with boosting appear tuned to narrower spectral bandwidths and higher temporal modulation rates than when characterized with normalized reverse correlation. These differences have little impact on responses to speech, which is spectrally broadband and modulated at low rates. However, we find that models estimated by boosting also predict responses to non-speech stimuli more accurately. These findings highlight the crucial role of priors in characterizing neuronal response properties with natural stimuli. PMID- 17852751 TI - Artists portray human faces with the Fourier statistics of complex natural scenes. AB - When artists portray human faces, they generally endow their portraits with properties that render the faces esthetically more pleasing. To obtain insight into the changes introduced by artists, we compared Fourier power spectra in photographs of faces and in portraits by artists. Our analysis was restricted to a large set of monochrome or lightly colored portraits from various Western cultures and revealed a paradoxical result. Although face photographs are not scale-invariant, artists draw human faces with statistical properties that deviate from the face photographs and approximate the scale-invariant, fractal like properties of complex natural scenes. This result cannot be explained by systematic differences in the complexity of patterns surrounding the faces or by reproduction artifacts. In particular, a moderate change in gamma gradation has little influence on the results. Moreover, the scale-invariant rendering of faces in artists' portraits was found to be independent of cultural variables, such as century of origin or artistic techniques. We suggest that artists have implicit knowledge of image statistics and prefer natural scene statistics (or some other rules associated with them) in their creations. Fractal-like statistics have been demonstrated previously in other forms of visual art and may be a general attribute of esthetic visual stimuli. PMID- 17852753 TI - Salamander locomotion-induced head movement and retinal motion sensitivity in a correlation-based motion detector model. AB - We report on a computational model of retinal motion sensitivity based on correlation-based motion detectors. We simulate object motion detection in the presence of retinal slip caused by the salamander's head movements during locomotion. Our study offers new insights into object motion sensitive ganglion cells in the salamander retina. A sigmoidal transformation of the spatially and temporally filtered retinal image substantially improves the sensitivity of the system in detecting a small target moving in place against a static natural background in the presence of comparatively large, fast simulated eye movements, but is detrimental to the direction-selectivity of the motion detector. The sigmoid has insignificant effects on detector performance in simulations of slow, high contrast laboratory stimuli. These results suggest that the sigmoid reduces the system's noise sensitivity. PMID- 17852755 TI - Complex cell pooling and the statistics of natural images. AB - In previous work, we presented a statistical model of natural images that produced outputs similar to receptive fields of complex cells in primary visual cortex. However, a weakness of that model was that the structure of the pooling was assumed a priori and not learned from the statistical properties of natural images. Here, we present an extended model in which the pooling nonlinearity and the size of the subspaces are optimized rather than fixed, so we make much fewer assumptions about the pooling. Results on natural images indicate that the best probabilistic representation is formed when the size of the subspaces is relatively large, and that the likelihood is considerably higher than for a simple linear model with no pooling. Further, we show that the optimal nonlinearity for the pooling is squaring. We also highlight the importance of contrast gain control for the performance of the model. Our model is novel in that it is the first to analyze optimal subspace size and how this size is influenced by contrast normalization. PMID- 17852756 TI - Behavioural variant frontotemporal dementia: not all it seems? AB - BACKGROUND: The diagnosis of the behavioural variant of frontotemporal dementia (bvFTD) can be challenging. At present there is a paucity of prospective work addressing the specificity of current diagnostic criteria for bvFTD with respect to long-term outcome (i.e., false positives versus true positives). METHODS: Here we report two individuals who met current clinical criteria for bvFTD and who underwent detailed long-term clinical and neuropsychological follow-up. In addition, both had serial volumetric MRI and functional metabolic (FDG-PET) imaging separated by 5 years. RESULTS: One case had a slow clinical decline as well as both progressive atrophy and hypometabolism in a frontotemporal distribution, consistent with a neurodegenerative FTD syndrome. However, the second developed neither atrophy nor hypometabolism and remained clinically stable, a decade from symptom onset. CONCLUSION: We propose that these cases illustrate that while there may be a slow evolution in bvFTD, it is possible that some cases who meet current criteria may not have a neurodegenerative syndrome. If correct, this hypothesis has important implications for the current diagnostic criteria. A potential hierarchy for diagnostic certainty in bvFTD is suggested. PMID- 17852757 TI - Traumatic brain injury and the construction of identity: a discursive approach. AB - Using discourse analysis, this paper explores the co-construction of identity for individuals who have sustained a severe traumatic brain injury (TBI). An analysis of discourse, obtained through interviewing six adults with a TBI, each with one or two significant others, suggested four main interpretative repertoires which informed participants' co-construction of identity: "Medical model referencing", "dependence as intrinsic to TBI", "TBI as deficit" and "progression and productivity as key life-defining features". Medical model referencing is discussed in relation to the common, passive positioning of individuals with TBI, which often occurred in relation to memory loss. The construction of abandonment was also common, due to participants" dependence on the provision of specialist, expert services in the community. Clinical implications are discussed in terms of facilitating individuals in the co-constructing and re-authorship of more empowering and inclusive narratives and providing community services that promote meaningful social identities, separate from medical discourse. PMID- 17852758 TI - Reliability and normative data for the comprehensive assessment of prospective memory (CAPM). AB - The Comprehensive Assessment of Prospective Memory (CAPM) is a questionnaire designed to evaluate frequency of prospective memory (PM) failures in people with brain injury. The aims of this study were to investigate the psychometric properties of the CAPM, including test-retest reliability and internal consistency, and to establish normative data by comparing CAPM scores between groups on the basis of sex, age, and education. Data were collected on 95 people aged 15-60 years living in the community, with no history of brain injury, using the CAPM. The results showed that the test-retest reliability and internal consistency for the CAPM were within acceptable ranges, indicating that the CAPM provides a stable and homogenous measure of an individual's self-report of PM failures. Normative data are presented in two age groups based on the significant difference found between the age groups 15-30 years and 31-60 years. These established norms can be used to describe perceived or observed behaviours indicative of PM failure in patients with brain injury by comparing CAPM ratings from significant others with the norms. The CAPM questionnaire provides researchers or clinicians with a stable and reliable assessment option that specifically focuses on PM for individuals with brain injury. PMID- 17852759 TI - Learning face-name associations in early-stage dementia: comparing the effects of errorless learning and effortful processing. AB - Some recent studies suggest that errorless learning principles may be beneficial in memory rehabilitation for people with dementia, while others indicate that effortful processing may be more important. The present study compared the effects of four different learning techniques, varying in level of effort required and number of errors elicited, on free recall, cued recall and recognition of novel and previously known associations among people with early stage dementia. Ten participants with a diagnosis of early-stage Alzheimer's, vascular or mixed dementia learned novel and previously familiar face-name associations with each of four techniques--vanishing cues, forward cues, target selection, and paired associate learning--in a within-subjects design. All conditions produced significant learning for both novel and familiar associations. There were no significant differences between conditions, although mean scores were slightly higher for errorful conditions. Reducing errors did not produce any benefits. Enhancing level of effort had no significant effects for familiar associations, but high-effort conditions were significantly more effective than low-effort conditions in facilitating cued recall of novel associations. The results confirm that memory rehabilitation techniques can produce significant benefits, but do not support the view that error reduction during learning facilitates greater improvement in early-stage dementia. Effort enhancement may be more important, especially when learning novel associations. PMID- 17852760 TI - Treating deficits in emotion perception following traumatic brain injury. AB - The present research aimed to investigate whether social perception deficits commonly experienced in the adult traumatic brain injury (TBI) population can be successfully remediated through cognitive rehabilitation. Twelve outpatient volunteers (11 male, 1 female; age range 20-57 years) with severe, chronic TBI (mean length of post-traumatic amnesia 121 days, range 58-210 days; mean months post- injury 93.58, range 17-207 months) participated in a randomised controlled trial. Participants were randomly allocated to treatment and waitlist control groups following assessment on a range of emotion perception and psychosocial measures. Treatment comprised 25 hours, across 8 weeks, of a programme specifically designed to address emotion perception which incorporated a variety of remediation techniques shown to be effective with the TBI population. Results indicated that participants significantly improved both in judging basic emotional stimuli when presented in a naturalistic format (i.e., video vignettes) and in making social inferences on the basis of speaker demeanour. This is the first known treatment study dealing with emotion perception deficits in individuals with TBI. PMID- 17852761 TI - The dilemma of the control condition in experience-based cognitive and behavioural treatment research. AB - Rehabilitation using cognitive and behavioural treatment methods (i.e., experience-based interventions) faces particular challenges in improving its evidence base through rigorous studies such as randomised controlled trials (RCTs). Experience-based treatments are often complex, with multiple "active ingredients" that may be difficult to characterise. In addition to the difficulty in specifying treatment ingredients, experience-based rehabilitation researchers face challenges in designing or selecting appropriate control or comparison conditions to test the efficacy of complex treatments. Based on lessons learned in designing a cognitive-behavioural intervention for anger self-management for people with traumatic brain injury (TBI) for the National Institutes of Health (NIH)-funded TBI Clinical Trials Network, we review the advantages, disadvantages and applications of a variety of control conditions for experience-based interventions. We discuss controls in which active treatments are withheld (no treatment controls, waitlist controls, and placebo-analogue designs); controls that involve comparison to naturally occurring or devised usual care treatments; and conditions that compare active treatments (dismantling designs, dose controls, and equivalence trials). Recommendations for selecting and developing control groups that maximise both equipoise and participant enrolment/retention are discussed. PMID- 17852762 TI - Neglect treatment by prism adaptation: what recovers and for how long. AB - Previous findings showed that a prism adaptation (PA) treatment can induce a long lasting recovery of hemispatial neglect, at least up to five weeks after the end of the treatment programme (Frassinetti et al., 2002). The present study further evaluated the effects of PA by investigating: (1) the long-term duration of the benefits assessed one week, and one, three and six months after the treatment; (2) the generalisation of the effects to different visual and non-visual functions; and (3) the index of visuo-motor responses (adaptation effect or after effect) that better predict neglect recovery by PA. To these aims, 21 neglect patients were submitted to PA treatment for 10 daily sessions over a period of two weeks, and their performance was assessed for visual, tactile, proprioceptive, motor and oculomotor functions. The results showed a consistent and stable amelioration of visuo-spatial abilities, both for personal and extrapersonal space. The improvement seems to be partially multimodal, since an amelioration was found for tactile modality, but not for proprioception and motor functions. Finally, neglect amelioration appeared to depend on patients' ability to adapt to prism optical displacement during the fist week of PA, since patients who were not able to correct pointing errors under prism exposure in the first week of treatment showed less neglect and oculomotor system recovery at the end of treatment. PMID- 17852763 TI - Elaborated spaced-retrieval and prospective memory in mild Alzheimer's disease. AB - Prospective memory, or the timely remembering of a planned action, is conceptualised as a cognitive process demanding episodic memory and executive attention. Impairments in these skills are characteristic of the cognitive decline in early Alzheimer's disease, providing an expectation of prominent prospective memory difficulties in this population, and yet surprisingly, memory performance in early Alzheimer's disease has rarely been evaluated within a prospective memory framework. In a preliminary study we demonstrated that older adults with early Alzheimer's disease (n=14), as compared to healthy older adults (n=14), were significantly impaired in a simple experimental paradigm of prospective remembering (a text-reading task). In a subsequent intervention study, we investigated the efficacy of spaced-retrieval for improving the prospective remembering performance of older adults with early Alzheimer's disease (n=16) compared to healthy older adults (n=16) under two learning conditions: a spaced-retrieval technique alone or spaced-retrieval combined with elaborated encoding of task. The majority of the Alzheimer's disease group (63%) demonstrated benefit in prospective remembering in the combined condition as compared to spaced-retrieval alone. Participants with Alzheimer's disease who demonstrated better executive attention (Trail Making- set-shifting) and/or better retrospective memory (Hopkins Verbal Learning Test-Revised- recognition) were more successful in the combined learning condition. PMID- 17852764 TI - Adult recall of tobacco advertising on the Internet. AB - This study examined the prevalence and characteristics of New Jersey adults who reported seeing tobacco products advertised on the Internet and described the means by which these products were advertised. Data were analyzed from the New Jersey Adult Tobacco Survey (NJATS), a repeated, cross-sectional, random-digit dial telephone survey conducted with a statewide representative sample. We used logistic regression to determine factors associated with recall of tobacco Internet advertising, adjusting for demographics, smoking behavior variables, and receipt of tobacco industry direct mail. Participants included 3,930 adults who completed the 2001 NJATS, 4,004 adults who completed the 2002 survey, and 3,062 adults who completed the 2005 survey. The proportion of adult Internet users reporting exposure to tobacco product advertising on the Internet has increased each year (6.9% in 2001, 15.6% in 2002, 17.8% in 2005). Based on 2005 data, recall of tobacco product advertising on the Internet was higher among males young adults aged 18-24 years, Asians, adults who reported receipt of direct mail advertising, and adults with a postcollege education. In addition, adult Internet users most often reported seeing tobacco products advertised on the Internet via pop-up or banner ads (60.7%), followed by E-mail messages (24.6%), and Web sites (14.9%). Recall of tobacco advertising by Internet users increased between 2001 and 2005 and was particularly high among certain subgroups. An urgent need exists for expanded surveillance of Internet tobacco sales and marketing practices. PMID- 17852765 TI - Secondhand smoke exposure in Mexican discotheques. AB - This study describes the impact of exposure to secondhand smoke for subjects who spend time in a discotheque, by comparing within-subject baseline and postexposure urinary cotinine levels. A total of 100 nonsmoking volunteers from a central region of Mexico provided a urine sample before entering a discotheque and another sample an average of 6 hr after the end of exposure. Concentrations of cotinine and its metabolite, trans-3'-hydroxycotinine, were measured in the urine by liquid chromatography-mass spectrometry. In females the average preexposure level of urinary cotinine was 2.2 ng/ml, and the average postexposure level was significantly higher, at 15.7 ng/ml. In males the average preexposure level of cotinine was 3.7 ng/ml, compared with 49.1 ng/ml in the postexposure assessment. The highest postexposure values were found in men younger than 22 years old with a value of 469.5 ng/ml. Exposure to secondhand smoke is a serious health risk. Our findings are important given that many of our subjects were exposed to substantial amounts of secondhand smoke in discotheques, as evidenced by the high urinary cotinine and 3'-hydroxycotinine concentrations. These findings support the need to prohibit smoking in discotheques to protect nonsmokers' health. PMID- 17852766 TI - Misclassification of maternal smoking status and its effects on an epidemiologic study of pregnancy outcomes. AB - Reliance on self-reported smoking status among pregnant women can result in exposure misclassification. We used data from the Calcium for Preeclampsia Prevention trial, a randomized study of nulliparous women conducted from 1992 to 1995, to characterize tobacco exposure misclassification among women who reported at study enrollment that they had quit smoking. Urinary cotinine concentration was used to validate quit status, and factors associated with exposure misclassification and the effects of misclassification on associations between smoking and pregnancy outcomes were evaluated using logistic regression. Of 4,289 women enrolled, 508 were self-reported smokers and 771 were self-reported quitters. Of 737 self-reported quitters with a valid cotinine measurement, 21.6% had evidence of active smoking and were reclassified as smokers. Women who reported having quit smoking during pregnancy were more likely to be reclassified than women who reported quitting before pregnancy (p<.001). Among smokers, factors independently associated with misclassification of smoking status included fewer cigarettes smoked per day and fewer years smoked. After reclassification the odds ratio for a small-for-gestational-age birth among smokers decreased by 14%, and the smoking-related reduction in birth weight decreased by 15%. Effects of misclassification on the association with hypertensive disorders of pregnancy were present but less dramatic. In conclusion, use of self-reported smoking status collected at the time of study enrollment resulted in the introduction of bias into our study of smoking and pregnancy outcomes. The potential for this type of bias should be considered when conducting and interpreting epidemiologic studies of smoking and pregnancy outcomes. PMID- 17852767 TI - Stressful life events and smoking behaviors in Chinese adolescents: a longitudinal analysis. AB - The associations between stressful life events and smoking have been established among adolescents in the United States. However, whether these relationships are similar in adolescents from other non-Western cultures is unknown. Understanding these relationships in adolescents may help to provide opportunities to reduce the smoking rates in those cultures by providing positive coping methods that do not include smoking. In this longitudinal study, the associations between nine stressful life events scales and smoking behaviors were examined in a sample of Chinese adolescents. Six of these scales, positive school-related, negative school-related, positive family-related, positive peer-related, negative peer related, and negative health-related had significantly different means among females and males. Among males, positive school-related stress was a protective factor for smoking susceptibility. Among females, positive school-related stress was a protective factor and negative school-related stress was a risk factor for lifetime smoking, and negative family-related stress was a risk factor for smoking susceptibility. Findings indicate that smoking among male adolescents in China may not be the result of stress; however, in females stress may contribute to the decision to smoke. Future directions are discussed. PMID- 17852768 TI - Do increases in cigarette prices lead to increases in sales of cigarettes with high tar and nicotine yields? AB - We used scanner data on cigarette prices and sales collected from supermarkets across the United States from 1994 to 2004 to test the hypothesis that cigarette prices are positively correlated with sales of cigarettes with higher tar and nicotine content. During this period the average inflation-adjusted price for menthol cigarettes increased 55.8%. Price elasticities from multivariate regression models suggest that this price increase led to an increase of 1.73% in sales-weighted average tar yields and a 1.28% increase in sales-weighted average nicotine yields for menthol cigarettes. The 50.5% price increase of nonmenthol varieties over the same period yielded an estimated increase of 1% in tar per cigarette but no statistically significant increase in nicotine yields. An ordered probit model of the impact of cigarette prices on cigarette strength (ultra-light, light, full flavor, unfiltered) offers an explanation: As cigarette prices increase, the probability that stronger cigarette types will be sold increases. This effect is larger for menthol than for nonmenthol cigarettes. Our results are consistent with earlier population-based cross-sectional and longitudinal studies showing that higher cigarette prices and taxes are associated with increasing consumption of higher-yield cigarettes by smokers. PMID- 17852769 TI - Endotoxins in tobacco smoke: shifting tobacco industry positions. AB - In the 1980s, the tobacco industry started a campaign to divert attention away from secondhand tobacco smoke (SHS) as a major source of indoor air pollution in workplaces by highlighting the roles of other indoor air pollutants. The industry, working through "third parties," highlighted endotoxins, naturally occurring substances that cause numerous inflammatory reactions in humans, as an alternative explanation to SHS as causing indoor air problems. In 1995, Hasday and colleagues were the first to present findings that cigarette smoke contains significant quantities of endotoxins. This discovery surprised tobacco industry scientists. The 1999 publication of the full Hasday et al. findings received only limited media attention but got the full attention of Philip Morris scientists concerned about a new public health issue and a new basis for regulation of workplace smoking by the U.S. Occupational Safety and Health Administration, which already regulated workplace endotoxin exposures from other sources. Philip Morris undertook an internal endotoxin research project to test the Hasday et al. findings and to determine if endotoxin-free cigarettes were possible. Although experiments were conducted to remove endotoxin from the tobacco, there is no evidence that they were successful. Following confirmation of SHS as an important source of endotoxins, the scientist promoting endotoxins as an important indoor air pollutant for the tobacco industry softened his position on the role of endotoxins as indoor pollutants. The presence of endotoxins in SHS provides an additional mechanism for the adverse effects of SHS that should be researched further, and the risk of exposure should be assessed. PMID- 17852770 TI - Role of reactive nitrogen species in blood platelet functions. AB - Blood platelets, in analogy to other circulating blood cells, can generate reactive oxygen/nitrogen species (ROS/RNS) that may behave as second messengers and may regulate platelet functions. Accumulating evidence suggest a role of ROS/RNS in platelet activation. On the other hand, an increased production of ROS/RNS causes oxidative stress, and thus, may contribute to the development of different diseases, including vascular complications, inflammatory and psychiatric illnesses. Oxidative stress in platelets leads to chemical changes in a wide range of their components, and platelet proteins may be initial targets of ROS/RNS action. It has been demonstrated that reaction of proteins with ROS/RNS results in the oxidation and nitration of some amino acid residues, formation of aggregates or fragmentation of proteins. In oxidized proteins new carbonyl groups and protein hydroperoxides are also formed. In platelets, low molecular weight thiols such as glutathione (GSH), cysteine and cysteinylglycine and protein thiols may be also target for ROS/RNS action. This review describes the chemical structure and biological activities of reactive nitrogen species, mainly nitric oxide ((*)NO) and peroxynitrite (ONOO(-)) and their effects on blood platelet functions, and the mechanisms involved in their action on platelets. PMID- 17852771 TI - Thiosulfinates modulate platelet activation by reaction with surface free sulfhydryls and internal thiol-containing proteins. AB - Thiosulfinates are characteristic flavors of Allium vegetables, with a highly reactive S-S=O group, that we previously showed to inhibit platelet aggregation through calpain-dependent mechanisms. With the aim to clarify the mode of action of these redox phytochemicals, we studied their effect on extracellular free sulfhydryls in relation to their effect on platelet responses (Ca2+ signals, release reaction, and aIIb3 integrin activation state). At the platelet surface, thiosulfinate dose-dependently increased the basal level of free sulfhydryls, independently of protein disulfide isomerase activity. This generation of new free sulfhydryls was associated with: (i) a three fold increase in labeling of resting platelets with an anti ligand-induced binding site antibody and (ii) marked inhibition of subsequent aIIb3 activation by agonists. Thiosulfinates increased the basal intracellular Ca2+ level of platelets. In activated platelets, they markedly inhibited the Ca2+ mobilization independently of the external Ca2+, the calpain-induced SNAP-23 cleavage and the granule release. In platelet free systems, thiosulfinates inhibited the activity of purified calpain and the free sulfhydryl of glutathione without any reducing properties on disulfides. The results demonstrate for the first time that thiosulfinates rapidly interact with sulfhydryls both at the platelet surface and inside the cell on intracellular cysteine-proteins, especially calpain. Inhibition of free cysteine and glutathione in whole blood may also contribute to their anti aggregant properties. Such sulfur compounds are of interest for the development of a new class of antithrombotic agents. PMID- 17852772 TI - The effect of rosuvastatin treatment on the mean platelet volume in patients with uncontrolled primary dyslipidemia with hypolipidemic diet treatment. AB - Platelet activation and aggregation are central processes in the pathophysiology of coronary heart disease. Mean platelet volume (MPV), a determinant of platelet activation, is a newly emerging risk marker for atherothrombosis. Rosuvastatin, a new hydrophilic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), is approved as an adjunct to diet in patients with dyslipidemia. In this study, we evaluated the effects of rosuvastatin on the MPV levels in patients with uncontrolled primary dyslipidemia with hypolipidemic treatment. We selected 30 age, sex and body mass index matched patients with uncontrolled primary dyslipidemia and hypolipidemic diet treatment and 30 normolipidemic healthy subjects. Dyslipidemic patients were treated with 10 mg/day rosuvastatin for 12 weeks. Metabolic parameters and MPV were measured at baseline and after rosuvastatin treatment in dyslipidemic group. At baseline, the dyslipidemic group had significantly higher MPV levels than in the healthy control group (8.4 +/-1.2 fl vs. 8.1 +/-0 1.0 fl, p < 0.005). The level of MPV decreased significantly after rosuvastatin treatment from a mean of 8.4 +/- 1.2 fl to 8.1 +/- 1.3 fl, (p < 0.001). The changes in MPV levels with rosuvastatin treatment were not correlated to changes in plasma lipids (p > 0.05). In addition to its well-known hypolipidemic effect, rosuvastatin also possesses significant anti-platelet activation properties. This antiplatelet effect of rosuvastatin treatment could play a role in reducing cardiovascular complications in primary hyperlipidemic patients. PMID- 17852773 TI - Hypersensitivity of platelets to adenosine diphosphate in patients with stable cardiovascular disease predicts major adverse events despite antiplatelet therapy. AB - Enhanced platelet activity correlates with early markers of myocardial damage in patients with cardiovascular disease. However, the extent to which enhanced platelet function signals subsequent adverse clinical outcomes in patients with cardiovascular disease is unknown. Blood from patients with stable cardiovascular disease receiving aspirin (325 mg/day) as the only antiplatelet therapy was tested for closure time (CT) with the Dade PFA-100 Platelet Function Analyzer system collagen/adenosine diphosphate (ADP) [CADP] cartridge and platelet aggregometry using 10 microM ADP. This study intentionally focused on those patients defined as aspirin sensitive by previously established criteria of arachidonic acid- and ADP-induced platelet aggregometry, and separately by collagen/epinephrine (CEPI) CT using the PFA-100. Follow up averaged 22 months for the adverse clinical events of death, myocardial infarction or cerebrovascular accident. For aspirin sensitivity determined by aggregometry, patients with CADP CT < 90 seconds (125/296 = 42.2%) had a composite endpoint rate of 19.2% (24/125), while those with CADP CT 90 seconds (171/296 = 57.8%) had an endpoint rate of 5.3% (9/171). Patients with CADP CT <90 seconds had a relative risk (RR) of 3.65 (95% CI.: 1.76-7.57) for recurrent events and 6.56 (95% CI.: 1.93-22.35) for death compared to patients with CADP CT 90s. Nearly identical results were obtained when patients were categorized as aspirin sensitive by CEPI CT. Platelet aggregometry with 10 microM ADP yielded no significant RR for the selected outcomes. Platelet function testing using the PFA 100 system appears to identify a subgroup of stable cardiovascular disease patients with increased risk of major adverse events that is associated with hypersensitivity to ADP, regardless of apparently effective aspirin therapy. PMID- 17852774 TI - Clopidogrel anti-platelet effect: an evaluation by optical aggregometry, impedance aggregometry, and the platelet function analyzer (PFA-100). AB - Platelet aggregation inhibition by clopidogrel may be suboptimal in 4-30% of patients. Traditionally, optical aggregometry is used to assess clopidogrel's anti-platelet effects by inhibition of ADP-induced aggregation in platelet rich plasma. Red blood cells are an important source of ADP and, thus, are known to modulate platelet function. Because the whole blood aggregation by impedance method assesses platelet function in a physiological milieu, we compared clopidogrel response by this method with the optical method in platelet rich plasma (PRP) and the Platelet Function Analyzer (PFA-100). Platelet function studies were performed in 17 healthy subjects at baseline and after 10 days of clopidogrel intake (75 mg/day). Optical and impedance aggregometry were performed after addition of ADP (10 and 20 microM) and collagen (1 and 2 microg/mL). For PFA-100 analysis, whole blood closure time was measured in collagen-coated cartridges with ADP and epinephrine. All subjects except one showed a decrease in ADP-induced aggregation using both aggregation methods. However, ADP-induced platelet aggregation was significantly inhibited when assessed in whole blood as compared to the optical method (71+/- 34% vs. 34.2+/- 23%, p = 0.0002); this suggests that whole blood aggregometry is more sensitive in the detection of clopidogrel effect in the presence of red cells, which are known to modulate platelet function. The PFA-100 ADP closure time was slightly prolonged above the reference interval in only 5/17 (29%) subjects, suggesting that this instrument is not able to detect clopidogrel effect. We conclude that whole blood aggregation appears to be more sensitive in detecting clopidogrel effect compared with the platelet rich plasma method; the PFA-100 was unable to detect clopidogrel effect in the majority of the subjects. PMID- 17852775 TI - Increased platelet activation markers in rheumatoid arthritis: are they related with subclinical atherosclerosis? AB - Atherosclerotic cardiovascular mortality is increased in rheumatoid arthritis (RA) patients. We evaluated the association of inflammatory response with platelet, endothelial, coagulation activation parameters; and subclinical atherosclerosis in RA patients. We included 27 RA patients (21 female; six male) and 19 healthy subjects (14 female; five male). Disease activity score (DAS28) in RA patients was calculated; and patients were divided into two groups as active and inactive. Flow cytometry was used to determine platelet CD62P expression, platelet microparticles (PMP), platelet-monocyte (PMC) and platelet-neutrophil complexes (PNC). Plasma E-selectin, thrombin-antithrombin (TAT) complex, and serum sCD40L levels were determined by ELISA. The intima-media thickness (IMT) of carotid arteries was determined by B-mode ultrasonography. In RA patients, platelet CD62P expression (p < 0.001), PMC (p = 0.037) and sCD40L (p < 0.001) levels were increased when compared to the control group. PNC (p = 0.07) and TAT levels (p = 0.1) were non-significantly higher, and PMP level (p = 0.075) was nonsignificantly lower in RA patients. Soluble E-selectin level was significantly higher in the active RA group than in the inactive RA group (p = 0.009). There was no correlation between carotid IMT and activity markers, the evaluated parameters (p > 0.05).The increase in markers of active platelets, CD62P and sCD40L, and PMC levels might be associated with the increased cardiovascular mortality in RA. Nevertheless, none of these parameters were associated with carotid IMT: this suggests that one cross-sectional value might not be a good marker for atherosclerosis PMID- 17852776 TI - The association of mean platelet volume levels with hypertensive retinopathy. AB - The pathophysiological mechanism of hypertensive retinopathy (HR) is not fully established. Elevated blood pressure alone does not fully account for the extent of retinopathy so other pathogenic mechanisms may be involved, such as increased platelet activation. Mean platelet volume (MPV) is a marker of platelet activation. Therefore, this study was designed to answer the following questions: Do MPV levels change in HR? and is there any relation between degree of HR and MPV levels? This study included newly diagnosed and 57 untreated essential hypertensive patients with HR. The hypertensive patients were divided into two groups according to the Keith, Wagener classification. Group 1 comprised 29 hypertensive patients with grade 1 HR with a mean age of 56.8 +/- 9.7 years. Group 2 comprised 28 hypertensive patients with grade 2 HR with a mean age of 58.1 +/- 10.3 years. Twenty-seven normotensive subjects who were the healthy participants and had undergone the check-up program were used as the control group. Fundoscopic examination, metabolic parameters and MPV levels were measured in all groups. The level of MPV in group 2 was significantly higher than in group 1 (8.9 +/-0 0.8 fl vs. 8.3 +/- 0.8 fl, p = 0.02) and the normotensive control group (8.9 +/- 0.8 fl vs 7.8 +/- 0.7 fl, p < 0.001). It was also higher in group 1 than in normotensive control group (8.3 +/- 0.8 fl vs.7.8 +/- 0.7 fl, p < 0.01). In addition, MPV showed a positive correlation with the degree of HR in the hypertensive group (r = 0.41, p = 0.015). Our study suggests that platelet activation, a mechanism known to be involved in vascular lesions, may promote the development of HR. PMID- 17852777 TI - Gait changes over time in stance control orthosis users. AB - This report presents objective motion analysis measurements of 14 stance control orthoses (SCO) users during a prospective open-enrollment 6-month clinical field trial. Participants were fitted with a Dynamic Knee Brace System (DKBS) which is a novel electromechanical SCO developed by the authors. Seven of the 14 subjects that had been prescribed but did not use a KAFO at the time of enrollment were defined as novice users. Those subjects who at the time of enrollment were using a locked KAFO for ambulation were defined as experienced users. Results showed that all subjects significantly increased peak knee flexion from 49.0 +/- 15.5 degrees to 55.9 +/- 11.4 degrees between the initial and six month tests (p = 0.02). They also tended to increase peak hip flexion from 39.6 +/- 13.4 degrees to 46.0 +/- 14.5 degrees between the 3 month and 6 month tests (p = 0.09). Novice users significantly increased velocity from 74.7 +/- 19.4 cm/s to 81.2 +/- 19.0 cm/sec between the initial and 3-month tests (p = 0.005). These same users increased stride length from 109 +/- 15.3 cm to 112 +/- 16.6 cm over the same time period (p = 0.008). Experienced KAFO users, however, tended to increase velocity from 68.8 +/- 20.5 cm/s to 83.2 +/- 16.8 cm/s at 3 months (p = 0.06). This was combined with a significant increase in cadence from 76.2 +/- 14.1 steps/min to 83.9 +/- 8.3 steps/min between the initial and 3 month tests (p = 0.05). Joint kinetics showed no changes for users over the duration of the testing period. These results indicate that KAFO users make significant gains in temporodistance measures, while changes in joint kinematics take longer to develop. PMID- 17852778 TI - Children with limb deficiencies: demographic characteristics. AB - The aim of this study is to determine the demographic data for amputations in children in relation of age, sex, level and cause of amputation. Data were collected from the records of amputees who attended the prosthetic clinic at the Royal Rehabilitation Center, King Hussein Medical Centre, Jordan, between 1 January 1995 and 31 December 2005. Demographic data (age, sex, level and cause of amputation) were analyzed. Some 120 children with different levels of amputation were included with mean age of 6.2 years. There were 64 (53.3%) males and 56 (46.7%) females. Male to female ratio was 1.15:1. The dominant level of amputation was trans-radial in 10 patients (15.62%) in the upper limb and trans tibial in 18 patients (28.12%) in the lower limb. The dominant cause of amputation was congenital deficiency in 56 patients (46.67%) followed by trauma in 48 (40%). The results of this study presented greater similarities to others in the literature, congenital limb deficiency being the dominant cause of amputation in children. This study helps in planning the needs for materials and budgets for the treatment of amputee children in Jordan. PMID- 17852779 TI - Usefulness of BNP-administration in cardiac surgery: animal model. AB - OBJECTIVE: The pharmacologic properties of Brain natriuretic peptide make it a favourable substance to use after cardiac operations. The goal of this study was to evaluate the effect of BNP following cardio-pulmonary bypass (CPB). METHOD: Nineteen pigs were operated on using CPB. One group received BNP and the control group received placebo. A 30-minute ischemic episode was simulated. Following declamping, BNP was administered by an IV bolus, followed by an infusion for 60 minutes. Hemodynamic and clinical chemistry parameters were documented, as well as the amount of catecholamines. RESULTS: The Cardiac output and Cardiac Index in the BNP group were significantly higher 60 minutes after ending CPB. Seven of ten animals in the control group needed catecholamines at the end of the experiment, whereas none of the animals in the BNP group did at this juncture. Creatine kinase and Lactate were significantly lower. CONCLUSION: BNP is a well-tolerated agent that could present a new treatment option for heart failure following cardiac surgery. Hemodynamics are greatly improved with almost no need for pharmacological support. PMID- 17852780 TI - Epidermal growth factor levels are related to diastolic blood pressure and carotid artery stiffness. AB - OBJECTIVES: The epidermal growth factor (EGF) is believed to be involved in vascular remodelling. EGF receptors are expressed in human atherosclerotic tissue. DESIGN: In order to study the role of EGF in vascular remodelling and early progression of atherosclerosis, 17 men and 16 women aged 20 to 45 years were recruited. Common Carotid Artery Stiffness index (CCA SI) and blood pressure were evaluated. In addition, serum levels of EGF and blood lipids were measured. RESULTS: The levels of serum EGF were significantly correlated to diastolic blood pressure (p<0.05) and CCA SI (p<0.05). Subjects with EGF concentrations in the upper median had significantly lower levels of HDL (High Density Lipoproteins) (p<0.05) and ApoA1 (Apolipoprotein) (p<0.05) than those with EGF concentrations in the lower median. DISCUSSION: High serum level of EGF is associated with elevated diastolic blood pressure and increased vessel stiffness suggesting a possible functional role of EGF in the cardiovascular system in a healthy population. PMID- 17852781 TI - Effect of lifestyle and/or statin treatment on soluble markers of atherosclerosis in hypertensives. AB - OBJECTIVES: To investigate the independent and combined effects of lifestyle changes and statin treatment on soluble markers of atherosclerotic activity. DESIGN: The study was a randomised, 2 x 2 factorial 1 year intervention trial. Participants (n=177) were sedentary, drug-treated, hypertensive men (aged 40-74 years). They were randomised to placebo, lifestyle intervention (diet and physical activity), fluvastatin 40 mg, or the combination of lifestyle and fluvastatin. RESULTS: Lifestyle intervention significantly reduced intercellular adhesion molecule-1 (sICAM-1) compared to usual care (p=0.003). Thrombomodulin level remained higher among individuals receiving lifestyle intervention (p=0.025). sICAM-1 was less reduced among fluvastatin treated participants compared to the placebo treated (p=0.029). Changes of blood pressure, weight or waist circumference were not significantly different between treatment groups. Individuals who achieved improvement of classical risk factors also had a significant reduction of endothelial markers (E-selectin, von Willebrands factor, tissue plasminogen activator antigen). CONCLUSIONS: One year of lifestyle intervention reduced the level of sICAM-1 in sedentary, drug-treated hypertensives, in spite of no impact on traditional risk factors. Low dose fluvastatin had no beneficial effect on the measured markers. PMID- 17852782 TI - The relationship between ASAT, CKMB, troponin-T and mortality after cardiac surgery. AB - OBJECTIVE: To investigate the relationship between ASAT, CKMB, troponin-T and mortality after cardiac surgery. DESIGN: ASAT, CKMB and TnT were analysed in 116 patients. Correlation, sensitivity, specificity and predictive values for permanent myocardial injury (defined as TnT > or = 2.0 microg/l postoperative day four) were calculated. In the second part our clinical protocol (ASAT on postoperative day 1 and TnT on day 3-4 in patients with ASAT above 2.5 microkat/l) was evaluated. Mortality was compared between patients with ASAT < 2.5 microkat/l (ASAT-), 2. ASAT > or = 2.5 microkat/l and TnT < 2.0 microg/l (ASAT+/TnT-) and 3. ASAT > or = 2.5 microkat/l and TnT > or = 2.0 microg/l (ASAT+/TnT+). RESULTS: Both ASAT and CKMB had irrespectively of cut-off level, low positive and high negative predictive value of permanent myocardial injury. Early and mid-term mortality did not differ significantly between ASAT- and ASAT+/TnT- patients. CONCLUSIONS: ASAT and CKMB can be used to exclude but not to diagnose permanent myocardial injury after cardiac surgery. Increased postoperative ASAT in the absence of increased TnT is not associated with worse clinical outcome than after normal postoperative ASAT. PMID- 17852783 TI - Left ventricular hypertrophy persists after successful treatment for coarctation of the aorta. AB - OBJECTIVES: To evaluate cardiac size and function in patients with coarctation of the aorta (CoA) before and after treatment. DESIGN: Ventricular size and function were examined by 2- and 3-dimensional echocardiography, and concentrations of natriuretic peptides measured in 15 paediatric patients before repair, and one, 6, and 12 months thereafter. Controls comprised 15 children. RESULTS: Before repair, mitral inflow velocities and left ventricular (LV) size and wall thickness were higher in patients. Thicknesses of interventricular septum and LV posterior wall decreased after repair but increased to initial level one year thereafter. The LV end-diastolic diameter remained larger than in controls despite successful repair. The size of right ventricle increased and levels of natriuretic peptides decreased during follow-up. Levels of natriuretic peptides correlated with the smallest diameter of CoA segment and diastolic indices of LV function. CONCLUSION: LV hypertrophy persists and LV size remains larger than in controls after successful repair even in normotensive patients with normal growth of CoA segment. This may be due to remodelling of ventricles and the aorta caused by CoA. PMID- 17852784 TI - TNFR gene-modified mesenchymal stem cells attenuate inflammation and cardiac dysfunction following MI. AB - OBJECTIVES: To investigate the protective effect of tumor necrosis factor receptor (TNFR) gene modified mesenchymal stem cells (MSCs) transplantation against inflammation and cardiac dysfunction following acute myocardial infarction (AMI). DESIGN: MSCs were extracted from the tibias and femurs of rats and transfected with recombinant adeno-associated viral (rAAV) expressing EGFP (enhanced green fluorescent protein) or p75 (human 75 kilodalton) TNFR at multiplicity of infection of 10(5) particles/cell. Rats with AMI induced by occlusion of the left coronary artery were randomized to MSCs-TNFR transplantation group, MSCs-EGFP transplantation group and MI control group. RESULTS: The effects of MSCs-TNFR transplantation on cardiac inflammation and left ventricular dysfunction were observed after 2 weeks of MI. We found that: 1) MSCs-TNFR transplantation attenuated protein production and gene expression of inflammatory cytokines TNF-, IL-1beta and IL-6; 2) MSCs-TNFR transplantation inhibited cardiomyocytes apoptosis and 3) MSCs-TNFR transplantation improved left ventricular function. CONCLUSIONS: The experimental data show that transplantation with rAAV-TNFR transfected MSCs improves left ventricular function following MI through anti-apoptotic and anti-inflammatory mechanisms. PMID- 17852785 TI - Gene expression of kinin receptors B1 and B2 in PBMC from patients with cardiac syndrome X. AB - INTRODUCTION: Cardiac syndrome X (CSX) is defined by typical chest pain, ST segment depression on ECG and normal coronary angiography. Pathology of CSX may involve microvascular dysfunction related to inflammation and abnormal pain sensitivity. Kinins are labile peptides participating in vasodilation, inflammation and pain. Their effects are mediated by two receptors: B1 and B2. The aim of the study was to assess gene expression of kinin receptors in peripheral blood mononuclear cells (PBMC) from patients with CSX. METHODS: The study was carried out in 34 patients with cardiac syndrome X, 13 with unstable angina and ten healthy subjects. Total mRNA was extracted from PBMC and the number of mRNA copies was assessed by quantitive reverse transcriptase polymerase chain reaction. RESULTS AND CONCLUSION: The study showed 7-fold higher transcriptional activity of B1R in CSX vs. control and 3.5 higher vs. UA. B2R expression was 2.5-fold higher in CSX group vs. control and UA, while in the letter two groups it was similar. Such disturbance in kinin signaling may participate in local vasoconstriction and may reflect disturbances in kinin signaling leading to nociceptive disturbances in these patients. PMID- 17852786 TI - Depressive symptoms and six-year cardiovascular mortality in elderly patients with and without heart failure. AB - OBJECTIVES: To evaluate whether depressive symptoms (DS) in elderly patients with heart failure (HF) in the community is associated with increased mortality. DESIGN: A cohort of 510 elderly patients (65-82 years) in a primary healthcare setting with symptoms associated with HF underwent a clinical and echocardiographic examination. A left ventricular ejection fraction (LVEF) <40% indicated HF. The mental health index scale was used to screen for DS. Cardiovascular and all-cause mortality was registered over 6 years. RESULTS: After adjustments those with DS had an increased risk (HR) of 3.0 (CI 95% 1.6 5.5, p=0.0001) and 2.2 (CI 95% 1.3-3.7, p=0.0004) of cardiovascular and all-cause mortality, respectively. Patients with HF and DS had the highest risk of cardiovascular mortality, HR 15.7 (CI 95% 4.8-52.2) compared to patients with HF without DS and those with LVEF > or = 50% and normal left ventricular diastolic function with and without DS. CONCLUSION: DS in elderly patients with HF is independently associated with increased mortality. Screening for DS is recommended as part of the clinical routine in managing patients with HF. PMID- 17852787 TI - Computed tomography of the coronary arteries: an alternative? AB - Multislice Computed Tomography Coronary Angiography (CTCA) has emerged as a promising non-invasive modality for the detection of coronary artery stenosis. Image quality is still limited when compared to conventional coronary angiography. However, CTCA has been demonstrated to be highly reliable to rule out coronary artery stenosis. Technological improvements and the combination of CTCA with other non-invasive modalities are expected to further increase diagnostic accuracy. Although CTCA has clearly left the research environment, the precise role of CTCA in the diagnostic work-up of coronary artery disease needs further research. PMID- 17852788 TI - Low perfusion pressure during CPB may induce cerebral metabolic and ultrastructural changes. AB - BACKGROUND: Recently we reported on cerebral metabolic changes suggesting ischemia in piglets during nitroprusside-induced low-pressure CPB. We here investigated whether a mean arterial pressure (MAP) of 40-45 mmHg could provoke similar changes by a NO-independent intervention. METHODS: Piglets underwent 60 minutes normothermic followed by 90 minutes hypothermic CPB. The LP-group (n=8) had MAP of 40-45 mmHg by phentolamine while the HP-group (n=8) had MAP of 60-80 mmHg by norepinephrine. Cerebral glucose, lactate, pyruvate and glycerol were determined. In the last two animals of each group, cerebral tissue was examined by electron microscopy. RESULTS: Cerebral lactate was higher in the LP-group than the HP-group during normothermic CPB. Compared with baseline, cerebral glucose of the LP-group decreased whereas lactate/pyruvate-ratio, lactate and glycerol concentrations increased during normothermic CPB. In the HP-group these parameters remained unchanged. Electron microscopy showed 31.2% and 8.3% altered mitochondria in the cortical micrographs taken from the LP- and the HP-group, respectively (p<0.001). CONCLUSION: MAP below 45 mmHg during CPB was associated with cerebral biochemical and morphological changes consistent with anaerobic metabolism and subcellular injury. PMID- 17852789 TI - Hypercoagulability and platelet inhibition after OPCAB. Randomized intervention with clopidogrel. AB - OBJECTIVE: Data on graft patency after Off-Pump Coronary Artery Bypass (OPCAB) suggest that the incidence of early graft closure is not increased compared to conventional coronary artery bypass surgery. However, hypercoagulability following OPCAB is still of concern, and acetylsalicylic acid as thromboembolic prophylaxis might be insufficient in the first weeks following OPCAB surgery. DESIGN: Twenty nine patients were randomly assigned to+/- 75 mg of clopidogrel until 30 days after OPCAB surgery. The follow-up time was 2 months including standard blood samples and thrombelastography (TEG) with a specific platelet inhibition assay, which was evaluated as a part of the study. RESULTS: In both groups a significant increase in TEG maximum amplitude was found 5 days after surgery. Platelet inhibition showed great variations but was significantly increased in the clopidogrel group (34.1%) vs. control group (11.0%) after 1 month. CONCLUSION: Hypercoagulability was seen 5 days after OPCAB and could not be demonstrated after 1 month. No clinical effects of the hypercoagulability were observed, and further research is needed to determine if clopidogrel should be recommended after OPCAB. PMID- 17852790 TI - Alpha-2 adrenergic antagonism enhances risk of ventricular tachycardia during acute ischemia. AB - OBJECTIVE: In this study we tested the hypothesis that alpha-2 adrenergic antagonism could facilitate induction of previously non-inducible ventricular tachycardia (VT) during acute ischemia. Previous reports suggest that VT during ischemia may be modulated by (alpha-2 adrenergic agonists. DESIGN: The left anterior descending artery was occluded after instrumentation of the ischemic risk zone with 21 multipolar plunge needles, each recording 6 bipolar electrograms. Three dimensional mapping characterized the mechanism of VT induced with extrastimuli. RESULTS: Of 16 non-inducible dogs included, eight which were given the alpha-2 adrenergic antagonist yohimbine all had inducible VT, while all eight in the control group remained non-inducible (p < 0.05). Six of the VTs were of focal Purkinje origin. The cycle length of the VTwas 119 +/- 4 ms. Mean arterial pressure (81+/- 8 to 82 +/- 8 mmHg, p = ns), ventricular effective refractory period (146 +/- 6 to 144 +/- 5 ms, p = ns) and ischemic zone size (55 +/-6% vs. 61 +/- 4%, p = 0.45) were not altered by yohimbine indicating minimal central or pre-junctional effects of the drug. CONCLUSIONS: Yohimbine facilitates induction of VT, especially those with focal Purkinje fiber origin, suggestive of an effect mediated through antagonism of post-junctional alpha-2 adrenoceptors on Purkinje fibers. PMID- 17852791 TI - Gender-related differences in the management of non-ST-elevation acute coronary syndrome patients. AB - OBJECTIVES: To compare management and outcome of female and male non-ST-elevation acute coronary syndrome (ACS) patients. DESIGN: FINACS Studies are prospective registries of non-ST-elevation ACS patients conducted in 2001, 2003, and 2005 in nine hospitals. RESULTS: The studies enrolled 1,399 patients from which 39% were women. During hospitalisation women were treated less often than men with aspirin (odds ratio [OR]) for women 0.60, 95% confidence interval [CI] 0.41 to 0.88, p=0.03). Women underwent less often in-hospital coronary angiography than men (adjusted OR 0.71, 95% CI 0.55 to 0.93, p=0.01). Also in the subgroup of younger (<75 years) high-risk patients, female sex was independent predictor for not performing in-hospital angiography (OR 0.64, 95% CI 0.42 to 0.97, p=0.04). Age adjusted mortality at 6 months was similar between men and women. CONCLUSIONS: Compared to men women received less often aspirin. Women were referred less often to in-hospital coronary angiography. Under-use of in-hospital angiography was evident also in patients with high-risk features when guidelines recommend early invasive treatment. PMID- 17852792 TI - Effect of acute changes in oxygen tension on flow-mediated dilation. Relation to cardivascular risk. AB - OBJECTIVE: Oxygen-dependent changes in vascular diameters may be detrimental when the endothelium is dysfunctional. DESIGN: Endothelial responsiveness was evaluated by brachial ultrasound and flow-mediated/nitroglycerin-mediated dilation (FMD/NMD). FMD/NMD was investigated in males with increased risk of cardiovascular disease (mean age 44+/-2 years, n=10) and matched controls without risk factors (44+/-2 years, n=10). FMD/NMD was assessed during normoxia (21% O2, 79% N2), while inhaling hypoxic gas (12.5% O2, FMDHyp/NMD), and 100% O2 supplementation (FMDO2/NMD). In a second study we addressed the effect of lipid lowering. Twenty persons with cardiovascular risk (mean age 50+/-2 years) were treated with atorvastatin (80 mg/day) and FMD/NMD was measured during normoxia, hypoxia and oxygen supplementation before, after 1 day and 3 months. RESULTS: Oxygen supplementation evoked vasoconstriction, while FMDHyp/NMD was reduced compared to FMD/NMD. Atorvastatin significantly lowered total cholesterol, LDL cholesterol, and ADMA after 1 day of treatment, while triglycerides, ApoB and hsCRP were lowered after 3 months. Atorvastatin did not change FMD/NMD irrespective of oxygen tension. CONCLUSION: Irrespective of risk factors or atorvastatin, hypoxia reduced endothelial vasodilation while oxygen supplementation evoked vasoconstriction. PMID- 17852793 TI - New mini-extracorporeal circulation system (ECC.O) is a safe technique in coronary surgery. AB - OBJECTIVES: Cardiopulmonary bypass (CPB) is known to cause the systemic inflammatory reaction after cardiac surgery. New coated and closed loop circuit systems may reduce this inflammation response and improve the surgical outcome. This study was designed to evaluate the safety and efficacy of the mini extracorporeal circulation system (ECC.O) in CABG patients. DESIGN: Forty patients undergoing elective coronary surgery were randomized into two groups, the ECC.O group and the standard CPB group. Routine hemodynamic monitoring and biochemical measurements were registered according to the hospital practice. RESULTS: The clinical outcome of the patients was similar in both groups. There were no significant differences between the groups in the duration of intubation following surgery, the length of intensive care unit-stay or the total hospital stay. The haemoglobin level was significantly higher (p=0.0069) during and after the perfusion in the ECC.O group. CONCLUSIONS: The ECC.O system can be safely used in CABG patients and it maintains haemoglobin level better than conventional CPB. PMID- 17852794 TI - Higher Thrombelastograph platelet reactivity in cardiac surgery patients than in blood donors. AB - OBJECTIVES: Platelet reactivity, evaluated by Thrombelastograph (TEG) predicts the recurrence of ischemic events in patients undergoing percutaneous coronary intervention (PCI). The aim of this study was to investigate the platelet hyperreactivity and the variability in platelet reactivity due to ADP in cardiac surgery patients and donors. METHODS: Preoperative blood samples from 22 patients undergoing CABG surgery and 43 blood donors were analysed by the TEG Platelet Mapping assay. Maximal platelet reactivity and platelet reactivity response to ADP stimulation (MAADP) were evaluated. RESULTS: Maximal platelet reactivity (MAThrombin) and MAADP was higher in the CABG patients than in the blood donors, p=0.001 for MAThrombin and p<0.0001 for MAADP. Six patients (27.2%) had a MAThrombin above the normal reference range compared to only one (2.3%) of the healthy donors (p=0.005). CONCLUSIONS: The identification of a higher subpopulation of CABG patients compared to donors presenting with platelet reactivity above the normal range together with increased platelet responsiveness to ADP may reflect the higher risk for ischemic events in this cohort. PMID- 17852795 TI - Fewer centers will increase quality and safety in cardiothoracic transplantation. PMID- 17852796 TI - Autoantibodies to the proteasome in monosymptomatic optic neuritis may predict progression to multiple sclerosis. AB - OBJECTIVE: Proteasome autoantibodies (PAB) have been found in multiple sclerosis (MS) patient sera and cerebrospinal fluid (CSF). Presence of PAB could thus be a possible diagnostic marker for MS. We investigated whether PAB serum status in acute monosymptomatic optic neuritis (ON) and MS differed significantly from that of healthy controls, and whether or not PAB status is predictive of later MS development in patients with ON. MATERIAL AND METHODS: Sera from ON patients, MS patients and healthy donors were analysed retrospectively using ELISA. Subsequently, a small group of PAB-positive samples were subjected to SDS-PAGE, immunoblotting and 2-D PAGE. RESULTS: We found that 20 % (6/30) ON patients, 47 % (22/47) MS patients and 9 % (7/81) controls tested PAB positive using ELISA analysis. High PAB levels were found in 2 (4 %) MS patients, 1 (3 %) ON patient and 2 (3 %) controls. PAB positivity in ELISA was confirmed by immunoblotting. Separation of proteasome subunits by 2D PAGE followed by immunoblotting revealed no particular PAB subunit preference. CONCLUSIONS: A retrospective search in available patient files revealed that 6 of 6 (100.0 %) PAB-positive ON patients developed MS over time. Eight of 24 (33 %) PAB-negative ON patients developed MS over time and 47 % (14/30) of all ON patients developed MS. A series of patient CSF was analysed by ELISA to assess the possible correlation between PAB status of concurrent serum and CSF samples, but no correlation was found. However, the results from the six PAB-positive ON patients could potentially be of prognostic value. PMID- 17852797 TI - Cardiovascular disease and type 2 diabetes mellitus: a multifaceted symbiosis. AB - Chronic hyperglycaemia (e.g. type 2 diabetes mellitus (T2DM) and prediabetes) in humans is associated with an increased risk of cardiovascular (CV) complications, and, vice versa, the presence of CV complications (e.g. myocardial infarction, stroke or intermittent claudication) among patients heightens the risk of T2DM or prediabetes. In both cases (i.e. chronic hyperglycaemia and CV complications), significant diagnostic and treatment challenges resulting from a broad range of factors may serve as barriers to reducing the deleterious societal impact of T2DM and prediabetes. These challenges often include clinicians: failing to intervene early and aggressively enough among patients with T2DM to achieve CV risk factor control; failing to efficaciously identify T2DM patients with already established CV complications; and failing proactively to assess individuals at high risk for T2DM. This review discusses the apparent symbiosis between CV disease and T2DM, with a focus on identifying patients with established T2DM or at risk for T2DM; traditional and novel risk factors and markers for CV disease in T2DM; challenges related to diagnosing CV disease in T2DM; and organization of T2DM care in order to prevent CV complications. These are issues that require attention because identifying patients at high risk for T2DM can halt or reduce their further glycaemic deterioration if addressed properly, and because novel markers and non invasive tests could be applied in patients with T2DM as a means of detecting and possibly treating unrecognized CV disease in time. Furthermore, several approaches for T2DM care can be effective in controlling the CV risk factors contributing to CV complications. PMID- 17852798 TI - The osmotic link between hypoglycaemia and hypovolaemia. AB - OBJECTIVE: Hypoglycaemia is regularly accompanied by hypovolaemia. To suggest a mechanism for this phenomenon, we reviewed data from eight studies conducted by our group and examined the circumstances under which rebound hypoglycaemia develops after intravenous infusion of glucose solutions. MATERIAL AND METHODS: Forty healthy volunteers and 40 patients received a total of 122 infusions of glucose solutions at different rates, volumes and concentrations. Plasma glucose and the haemodilution were measured repeatedly during and for at least 2 h after the infusions ended. Glucose kinetics was calculated using a one-compartment turnover model and the plasma volume expansion was estimated from changes in Hb. RESULTS: A strong linear correlation was found between the glucose level and the plasma volume expansion in all series of experiments (p<0.001). After infusion, there was a risk of hypoglycaemia and hypovolaemia developing in healthy volunteers with a high glucose clearance and when infusing glucose solutions of higher concentrations than 2.5 %. Few and mild hypoglycaemic events occurred in patients with insulin resistance, such as in diabetics and in those undergoing surgery. The immediate linear relationship between hypoglycaemia and hypovolaemia suggests an osmotic link between the two parameters. More specifically, infused fluid accompanies glucose during uptake into the cells, while volume expansion by the same fluid has already elicited an effective diuretic response. CONCLUSION: Hypovolaemia is a consequence of hypoglycaemia after intravenous infusion of glucose solution and is caused by the osmotic translocation of fluid from the extracellular to the intracellular fluid space that occurs despite effective renal elimination. PMID- 17852799 TI - Prediction of relative glomerular filtration rate in adults: new improved equations based on Swedish Caucasians and standardized plasma-creatinine assays. AB - OBJECTIVE: To evaluate newly developed equations predicting relative glomerular filtration rate(GFR) in adult Swedish Caucasians and to compare with the Modification of Diet in Renal Disease(MDRD) and Mayo Clinic equations using enzymatic and zero-calibrated plasma creatinine assays. MATERIAL AND METHODS: GFR was measured with iohexol clearance adjusted to 1.73 m(2). One population sample (n=436/Lund) was used to derive an equation based on plasma creatinine/age/gender, and a second with the addition of lean body mass (LBM). Both equations were validated in a separate sample (n=414/Malmo). The coefficients of the equations were eventually fine-tuned using all 850 patients and yielding Lund-Malmo equations without (LM) and with LBM-term (LM(LBM)). Their performance was compared with the MDRD(CC) (conventional creatinine calibration), MDRD(IDMS) (isotope dilution mass spectroscopy traceable calibration) and Mayo Clinic equations. RESULTS: The Lund equations performed similarly in both samples. In the combined set, the Mayo Clinic/MDRD(CC) resulted in +19.0/+10.2 % median bias, while bias for the other equations was < 10 %. LM(LBM) had the highest accuracy (86 % of estimates within 30 % of measured GFR), significantly (p < 0.001) better than for MDRD(IDMS) (80 %). In men with BMI < 20 kg/m(2), MDRD(IDMS)/LM had +46 %/+19 % median bias. MDRD(IDMS) also overestimated GFR by 22 %/14 % in men/women above 80 years of age. The LM(LBM) equation had < 10 % bias irrespective of BMI, age or GFR except for a 15 % negative bias at GFR > 90 mL/min/1.73 m(2). CONCLUSION: The newly developed Lund-Malmo equations for GFR estimation performed better than the MDRD(IDMS) and Mayo Clinic equations in a Swedish Caucasian sample. Inclusion of an LBM term improved performance markedly in certain subgroups. PMID- 17852800 TI - Temporal changes of the plasma levels of cystatin C, beta-trace protein, beta2 microglobulin, urate and creatinine during pregnancy indicate continuous alterations in the renal filtration process. AB - OBJECTIVE: To determine the plasma levels of the renal functional markers creatinine, urate, cystatin C, beta2-microglobulin and beta-trace protein in samples from the first, second, early third and late third trimesters of 398 healthy women with uncomplicated singleton pregnancies. MATERIAL AND METHODS: Plasma samples from 58 healthy non-pregnant women served as controls. The creatinine levels were significantly lower at all time-points in pregnancy, whereas the urate levels were lower during the first and second trimesters but increased in the late third trimester. The cystatin C, beta2-microglobulin and beta-trace protein levels displayed similar changes with increased levels in the third trimester but unaltered levels during the first and second trimesters. RESULTS: The results indicate an increased filtration of low-molecular weight molecules during pregnancy, particularly during the first and second trimesters, whereas filtration of 10-30 kDa molecules is decreased in the third but unaltered in the first and second trimesters. The levels of albumin and alph2-macroglobulin were measured in the same samples. CONCLUSIONS: The albumin levels decreased in the second and third trimesters, whereas the levels of chi2-macroglobulin were unchanged, which is compatible with a virtually unaltered transfer of chi2 macroglobulin between the intra- and extravascular space during pregnancy and a significantly increased extravascular fraction of albumin. PMID- 17852801 TI - Estimated glomerular filtration rate (eGFRCystC) from serum cystatin C shows strong agreement with iohexol clearance in patients with low GFR. AB - OBJECTIVE: Estimation of glomerular filtration rate (eGFR) is essential in the diagnosis and monitoring of patients with kidney disease and for correct dosage of drugs eliminated from the circulation by the kidneys. Cystatin C has been shown in several studies to be superior to creatinine in estimating eGFR. However, there are few studies on the performance of cystatin C estimated eGFR (eGFRCystC) in patients with advanced kidney disease and low GFR. MATERIAL AND METHODS: We measured serum cystatin C, together with serum creatinine, during iohexol clearance in patients with iohexol clearance below 30 mL/min/1.73 m2. The cystatin C values were used to calculate eGFRCystC using the formula eGFR (mL/min/1.73 m2) = 79.901*(cystatin C value in mg/L)-1.4389. RESULTS: There was good correlation between eGFRCystC and iohexol clearance (r = 0.88) in patients with iohexol clearance <30 mL/min/1.73 m2 and none of the patients had a difference between eGFRCystC and iohexol clearance exceeding 50 %. The Modification of Diet in Renal Disease (MDRD) equation and corrected MDRD eGFR showed a positive bias and weaker correlations with iohexol eGFR (MDRD = 5.32+1.22*iohexol clearance; corrected MDRD = 4.76+1.10*iohexol clearance; r = 0.59). For MDRD eGFR, 42 of 94 (44.7%) samples showed more than 50% difference to iohexol clearance. CONCLUSIONS: eGFRCystC is an efficient, practical and cost effective alternative to iohexol clearance in patients with reduced GFR. PMID- 17852802 TI - Potassium channel KCNH2 K897T polymorphism and cardiac repolarization during exercise test: The Finnish Cardiovascular Study. AB - OBJECTIVE: Cardiac repolarization is regulated, in part, by the KCNH2 gene, which encodes a rapidly activating component of the delayed rectifier potassium channel. The gene expresses a functional single nucleotide polymorphism, K897T, which changes the biophysical properties of the channel. The objective of this study was to evaluate whether this polymorphism influences two indices of repolarization--the QT interval and T-wave alternans (TWA)--during different phases of a physical exercise test. MATERIAL AND METHODS: The cohort consisted of 1,975 patients undergoing an exercise test during which on-line electrocardiographic data were registered. Information on coronary risk factors and medication was recorded. The 2690A>C nucleotide variation in the KCNH2 gene corresponding to the K897T amino acid change was analysed after polymerase chain reaction with allele-specific TaqMan probes. RESULTS: Among all subjects, the QTc intervals did not differ between the three genotype groups (p> or =0.31, RANOVA). Women with the CC genotype tended to have longer QT intervals during the exercise test, but the difference was statistically significant only at rest (p = 0.011, ANOVA). This difference was also detected when the analysis was adjusted for several factors influencing the QT interval. No statistically significant effects of the K897T polymorphism on TWA were observed among all subjects (p = 0.16, RANOVA), nor in men and women separately. CONCLUSIONS: The K897T polymorphism of the KCNH2 gene may not be a major genetic determinant for the TWA, but the influence of the CC genotype on QT interval deserves further research among women. PMID- 17852803 TI - Quality specifications for seminal parameters based on clinicians' opinions. AB - BACKGROUND: The aim of this study was to identify analytical quality specifications for seminal parameters based on clinicians' opinions, and to compare with those based on biological variability and state of the art. MATERIAL AND METHODS: Two questionnaires with case histories were sent to laboratories participating in the Spanish programme of external quality on semen analysis for distribution to as many specialist clinicians as possible. Our intention was to determine the critical difference (CD), defined as the difference needed between two consecutive results obtained from semen analysis to be 95 % confident that the two results actually are different. Subsequently, we calculated the specifications of analytical quality in accordance with the clinicians' opinions. RESULTS: The CDs obtained from the median value of the differences between the initial value and that given in the clinicians' replies were similar in clinical situations of improvement or worsening in the infertile normozoospermic male, and also in worsening situations for male patients presenting a significant alteration in seminal parameters. For improvement in this latter case, the CD cited as necessary in the clinicians' opinion was much higher than that for the other clinical situations. At a desirable level of quality, for concentration and total motility the coefficients of variation in the clinicians' opinion were below those based on biological variability and the state of the art. However, for type "a+b" motility, type "a" motility, morphology and vitality the coefficients of variation based on the clinicians' opinions were higher than those based on biological variability and lower than those based on the state of the art. CONCLUSIONS: Quality specifications for seminal parameters based on clinicians' opinions depend to a large extent on the clinical situation and on the seminal parameter being analysed. PMID- 17852804 TI - Determination of testosterone in serum by liquid chromatography-tandem mass spectrometry. AB - Commercial direct immunoassays for serum testosterone sometimes result in inaccuracies in samples from women and children, leading to misdiagnosis and inappropriate treatment. The diagnosis of male hypogonadism also requires an accurate testosterone assay method. We therefore developed a sensitive and specific stable-isotope dilution liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for serum testosterone at the concentrations encountered in women and children. Testosterone was extracted with ether-ethyl acetate from 250 microL or 500 microL of serum. Instrumental analysis was performed on an API 2000 tandem mass spectrometer in the multiple-reaction monitoring (MRM) mode after separation on a reversed-phase column. The MRM transitions (m/z) were 289/97 for testosterone and 291/99 for d(2) testosterone. The calibration curves exhibited consistent linearity and repeatability in the range 0.2-100 nmol/L. Interassay CVs were 4.2-7.6 % at mean concentrations of testosterone of 3.3-45 nmol/L. Total measurement uncertainty (U, k = 2) was 12.9 % and 13.4 % at testosterone levels of 2.0 nmol/L and 20 nmol/L, respectively. The limit of detection was 0.05 nmol/L (signal-to-noise ratio = 3) and the overall method recovery of testosterone was 95 %. Correlation (r) with our in-house extraction RIA was 0.98 and with a commercial RIA 0.92. Reference intervals for adult males and females in age groups 18-30, 31-50, 51-70 and over 70 years were established. Sensitivity and specificity of the LC-MS/MS method offer advantages over immunoassay and make it suitable for use as a high-throughput assay in routine clinical laboratories. The high equipment costs are balanced by higher throughput together with shorter chromatographic run times. PMID- 17852805 TI - Biomarkers of alcoholism: an updated review. AB - Alcoholic beverages, and the problems they engender, have been familiar in human societies since the beginning of recorded history. Among a variety of blood tests used to aid the diagnosis of alcohol consumption and related disorders, laboratory tests are particularly useful in settings where cooperativeness is suspected or when a history is not available. Biochemical and haematological tests, such as gamma-glutamyltransferase activity, aspartate aminotransferase activity and erythrocyte mean corpuscular volume, are established markers of alcohol intake. Carbohydrate-deficient transferrin is the only test approved by the FDA for the identification of heavy alcohol use. Total serum sialic acid and sialic acid index of Apolipoprotein J have the potential to be included in a combination of measurements providing an accurate, more exact, assessment of alcohol consumption in a variety of clinical and research settings. Several other markers with considerable potential for measuring recent alcohol intake include beta-hexosaminidase, acetaldehyde adducts and the urinary ratio of serotonin metabolites, 5-hydroxytryptophol and 5-hydroxyindoleacetic acid. These markers provide hope for more sensitive and specific aids to diagnosis and improved monitoring of alcohol intake. PMID- 17852806 TI - Renal effects of urodilatin in healthy subjects are independent of blockade of the cyclooxygenase and angiotensin II receptor. AB - OBJECTIVE: Little is known about the role of the renin-angiotensin-aldosterone system and the renal prostaglandins in modulating the renal vasoconstrictive and natriuretic effects of synthetic urodilatin (URO) in healthy humans. MATERIAL AND METHODS: Twelve volunteers were pretreated in a randomized, single-blind, crossover study with losartan 50 mg a day or placebo for 5 days. Another 12 healthy subjects received indomethacin 25 mg three times a day or placebo for 4 days and a single dose on day 5. All subjects received a URO infusion (15 ng kg( 1) min(-1)) on day 5. Radioactive tracers and the lithium clearance technique were used. RESULTS: The effective renal plasma flow (ERPF) decreased significantly during URO infusion: losartan pretreatment 573+/-63 to 461+/-76 mL/min versus placebo 540+/-89 to 432+/-90 mL/min. The urinary sodium excretion rate (UNa) increased significantly during URO infusion: losartan 335+/-115 to 502+/-134 umol/min (micromol/min) (UNa) versus placebo 386+/-142 to 476+/-137 umol/min (micromol/min) (UNa). In the indomethacin pretreated subjects, ERPF decreased significantly from 530+/-109 to 446+/-55 mL/min versus 533+/-89 to 449+/-69 mL/min in the placebo group. UNa increased significantly from 395+/-142 to 768+/-254 umol/min (micromol/min) (UNa) in the indomethacin group versus 282+/ 117 to 552+/-242 umol/min (micromol/min) (UNa) in placebo. CONCLUSION: The renal vasoconstrictive and natriuretic effects of synthetic URO are not modified by sustained inhibition of the angiotensin II receptor or the cyclooxygenase in man in a sodium replete state. PMID- 17852807 TI - Effect of smoking cessation on markers of inflammation and endothelial cell activation among individuals with high risk for cardiovascular disease. AB - OBJECTIVE: To prospectively determine the effect of smoking cessation on markers of inflammation and endothelial cell activation. MATERIAL AND METHODS: Thirty male and 22 female smokers of >7 cigarettes daily, aged 32-64 years with cardiovascular disease (CVD) or additional risk factors to smoking, participated in a program of smoking cessation with a follow-up period of 1 year. Cessation was validated by carbon monoxide measurement in expired breath, and 41 of the patients completed the study (17 quitters and 24 non-quitters). Plasma samples were drawn at baseline and after 1 year, and inflammatory markers were analyzed by enzyme immunoassays. Peripheral blood mononuclear cells (PBMCs) were isolated at baseline and 1 year in 6 quitters and 6 smokers and mRNA levels of interleukin 8 (IL-8), tumor necrosis factor x (TNFx) and intercellular adhesion molecule 1 (ICAM-1) were analyzed by real-time quantitative RT-PCR. RESULTS: Our main findings were: (i) While the concentration of soluble (s) ICAM-1 decreased in quitters, it increased in smokers, with a significant difference in changes between the groups (p=0.04). (ii) While there was only minor change in mRNA levels of IL-8 in smokers, those who stopped smoking showed a decrease in the gene expression of IL-8 (p < 0.09; comparing difference in changes). (iii) Concentrations of the other measured parameters (E-selectin, IL-6, sCD40 ligand, TNFx, von Willebrand factor, and C-reactive protein) were unchanged during follow up in both groups. CONCLUSION: Smoking cessation induced a reduction in ICAM-1, suggesting a novel mechanism for the rapid reduction in the risk of CVD following smoking cessation. PMID- 17852808 TI - Comparison of rocket and crossed immuno-electrophoresis assays for determination of the level of actin complexing of Gc globulin. AB - OBJECTIVE: Gc globulin (vitamin D-binding protein) is a component of the extracellular actin scavenger system. The level of Gc globulin is reduced in patients with fulminant hepatic failure, septic shock and trauma. Furthermore, low levels of Gc globulin in patients with fulminant hepatic failure and multiple trauma have been found to correlate with the morbidity and mortality of patients. Owing to a large increase in the turnover of Gc globulin upon complex formation with actin, it may be important to determine both the total Gc globulin concentration and the degree of complexing with actin for estimating the clinical prognosis of a patient. For this reason, we have compared a crossed immuno electrophoresis method (CIE), suitable for visualizing the degree of complexing with actin, with a rocket immuno-electrophoresis method (RIE), previously used for determination of the complex degree. MATERIAL AND METHODS: Sera from healthy donors and from patients with acetaminophen-induced liver disease or trauma were investigated using CIE, RIE and enzyme-linked immunosorbent assay (ELISA). RESULTS: Using the CIE, no Gc globulin-actin complexes were detected among healthy donors. Complexes were present in 21 of 39 patients with liver disease and 3 of 37 trauma patients. High complex ratios (> 20 %) were found in 6 of 7 patients with hepatic encephalopathy. Using the RIE, complexes were detected in most samples. CONCLUSION: The results show that the CIE method may be used for determining the degree of actin complexing in conjunction with ELISA or RIE in determining the levels of total Gc globulin. PMID- 17852809 TI - Faecal and serum levels of eosinophil cationic protein in a healthy paediatric population. AB - BACKGROUND: Eosinophil cationic protein (ECP) has been regarded as an excellent marker of eosinophil activation in various diseases where eosinophil-mediated inflammation plays a role. Recently, it has been suggested as a faecal marker of intestinal inflammation in several immune-mediated diseases with gastrointestinal expression. Owing to the scarcity of information at paediatric age, the establishment of reference values is necessary before further clinical studies. OBJECTIVE: To determine faecal and serum ECP levels in healthy children and their association with other biological parameters, thereby providing background additional validation data for this age group. METHODS: Faecal and serum ECP levels were available from healthy Caucasian children recruited at a regular outpatient clinic. Exclusion criteria were: chronic illnesses, acute illness, mucosal bleeding and recent pharmacological medication. Faecal and serum ECP levels and faecal a1AT were determined by commercial radioimmunoassay and serum IgE by fluoroenzyme immunoassay Uni-CAP. RESULTS: Mean and median faecal ECP levels were 1.93 microg/g and 1.20 microg/g, respectively (range 0.41 22.20),while the corresponding serum ECP levels were 13.50 microg/L and 9.54 microg/L, respectively (range 0.20-74.8). The cut-offs found were 2.80 microg/g and 16.89 microg/L for faecal and serum ECP, respectively. A significant (p=0.001) increase in serum, but not in faecal, ECP levels was found among patients with high peripheral eosinophil blood count. Neither faecal nor serum ECP levels were influenced by serum IgE levels. CONCLUSIONS: Faecal and serum ECP levels, as determined in the present study, add background information concerning reference levels at paediatric age for further studies indifferent clinical settings. PMID- 17852810 TI - Experimental hyperhomocysteinemia disturbs bone metabolism in rats. AB - OBJECTIVE: To investigate whether experimental hyperhomocysteinemia (HHCY) can induce adverse changes in bone metabolism. METHODS: Blood and urine samples were collected from rats fed with a methionine-enriched diet (HHCY, n = 18) or an isocaloric control diet (control, n = 10) for 12 weeks. Biochemical bone turnover markers (osteocalcin, hydroxyproline, N-terminal collagen I telopeptides and homocysteine (HCY), folate and vitamin B12) were measured. Whole body bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry. RESULTS: HCY was significantly higher in HHCY than in control rats (16.2 versus 3.2 micromol/L; p = 0.0006). Bone resorption parameters hydroxyproline (1.60 +/- 0.6 versus 0.85 +/- 0.4; p<0.05) and N-terminal collagen I telopeptides (150.8 +/- 78 versus 48.1 +/- 26 nmol/L BCE; p<0.05) increased, whereas bone formation marker osteocalcin (9.01 +/- 3.8 versus 15.07 +/- 4.2 ng/mL; p<0.05) decreased in HHCY compared to control rats. The relation N-terminal collagen I telopeptides/osteocalcin significantly increased in HHCY compared to control rats (13.14 +/- 3.1 versus 4.14 +/- 1.9). BMD measurement did not reveal any differences between groups. CONCLUSION: These findings demonstrate a significant modification of bone turnover in HHCY rats. The relation between bone resorption and formation indicates a shift toward bone resorption, which might be a plausible explanation for the relation between HHCY and fracture risk. PMID- 17852811 TI - Serum tumour markers in patients with chronic kidney disease. AB - OBJECTIVE. Tumour markers are widely used for monitoring cancer patients and for screening certain tumours. It has recently been shown that the concentrations of some tumour markers are higher in patients with chronic kidney disease (CKD) than in healthy subjects. We analysed the influence of renal function and hemodialysis treatment on the serum levels of CA19-9, CA125, alpha fetoprotein (AFP), CA15.3, CA72.4, CYFRA 21-1, neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC-Ag). MATERIAL AND METHODS: 232 non-dialysis patients with CKD and 37 uraemic patients treated with maintenance hemodialysis were enrolled in this study. The nondialysis patients were divided into three groups depending on their creatinine clearance (Ccr) levels: group 1 = Ccr < or =25 mL/min; group 2 = 25.1 49.9 mL/min; group 3 = Ccr > or =50 mL/min. For comparison, we chose 37 non dialysis patients with similar Ccr, age and same gender as controls. RESULTS: The serum concentrations of CA19-9, CA125 (male), CYFRA 21-1, NSE and SCC-Ag correlated negatively with Ccr, while there were no significant differences in the concentrations of CA125 (female), AFP, CA15.3, CA72.4. The serum levels of CA19-9, CA125, AFP, CA15.3, CA72.4, CYFRA 21-1, NSE and SCC-Ag showed no differences between hemodialysis patients and non-dialysis controls (p > 0.017). CONCLUSIONS: The increase in the serum levels of CA19-9, CA125 (in males), CYFRA 21-1, NSE and SCC-Ag in patients with CKD affects the specificity of these markers in the diagnosis of cancer. Hemodialysis does not affect the serum levels of CA19-9, CA125, AFP, CA15.3, CA72.4, CYFRA 21-1, NSE and SCC-Ag. PMID- 17852812 TI - External quality assessment in the measurement of haemoglobin by blood gas analysers in Belgium. AB - OBJECTIVE: The Belgian national External Quality Assessment Scheme (EQAS) for haematology organized a survey to assess the reliability of haemoglobin (Hb) measurements with the blood gas analysers (BGAs) currently available in Belgian hospitals. MATERIAL AND METHODS: All hospital laboratories received two specimens of fresh EDTA anticoagulated whole blood and were asked to determine the Hb concentration using both the conventional haematology analyser (HA) and all BGAs in the hospital. Ninety-seven hospital laboratories participated in the study and a total of 166 results were reported. The BGAs used (grouped according to technology) were Rapidlab 845, 855, 865 (Bayer 1, n = 41), Rapidlab 1245, 1265, Rapidpoint 405 (Bayer 2, n = 19), GEM Premier 3000 (Instrumentation Laboratory, IL, n = 13), ABL 500 and 600 series (Radiometer 1, n = 13), ABL 700 and 800 series (Radiometer 2, n = 35), Omni C, S5 (Roche 1, n = 7), Omni 3, 6, 9, S2, S4, S6 (Roche 2, n = 21). RESULTS: For the BGAs from Bayer, Radiometer and Roche, interlaboratory variation ranged from 0.6 % to 4.1 %, indicating good precision and close agreement between centres. A significant negative bias observed on the GEM Premier 3000 using the EDTA anticoagulated blood samples did not appear to be present in fresh heparinized whole blood samples. There was no significant difference in imprecision and bias between Hb measurements on BGA situated in and outside the central laboratory. PMID- 17852813 TI - Effect of freeze-thaw cycles on serum measurements of AFP, CEA, CA125 and CA19-9. AB - AFP, CEA, CA125 and CA19-9 are commonly used serum tumour markers (TMs) in clinical practice, although their quantification by immunoassay may be influenced by pre-analytical sample handling. Though the effect of repetitive freeze-thaw cycles is generally recognized, it is not clear in detail. The present study measured (CLIA) these TMs in serum samples freshly separated and after each of five freeze-thaw cycles, in which the samples were frozen at -40 degrees C for 10 months at cycle 4 and 2 h at other cycles. Statistical analysis with the General Linear Model for Repeated Measures revealed significant decreases in the measurements of the four TMs, with the least decrease of 6.8 % for CA125 and the most decrease of 18.2 % for CA19-9 after the last cycle, and an overwhelming single cycle decrease of mean 7.7 % at cycle 4 for AFP, CEA and CA125, of 7.5 % and 9.3 % at cycles 4 and 5 for CA19-9. So it seems that measurements of AFP, CEA and CA125 are more readily affected by long-term frozen storage compared with frequent freezing-thawing, while CA19-9 is relatively unstable under both conditions. PMID- 17852814 TI - Functional DNA repair system analysis in haematopoietic progenitor cells using host cell reactivation. AB - Deficiencies in individual DNA repair systems are involved in both de novo and therapy-related acute myeloid leukaemia (t-AML), as indicated by genetic markers involving nucleotide excision repair (NER gene polymorphisms), double-strand break (DSB) or mismatch repair (microsatellite instability (MSI)). We modified a host cell reactivation (HCR) assay for functional DNA repair system analysis of living primary haematopoietic cells; 2 x 10(5) normal peripheral blood lymphocytes (PBLs) and cord blood CD34+ progenitor cells were cryopreserved, thawed and transfected with 75-250 ng luciferase reporter plasmid (pCMVLuc) using DEAE-dextran (0.1 mg/mL) in a transfection volume of 250 microL. We obtained luciferase activities of approximately 300-fold above background in CD34+ progenitor cells and approximately 2000-fold in PBLs, thus rendering these cells applicable for DNA repair analysis. We then evaluated the NER (UV-irradiated pCMVLuc) and DSB repair capacity (linearized pCMVLuc) of normal lymphocytes and several leukaemic cell lineages. Kasumi-1 and HL-60 AML cells exhibited a reduced NER capacity compared to normal GM03715 lymphocytes, PBLs and CD34+ progenitor cells (6.2 +/- 0.9%, 6.5 +/- 0.9% vs. 12.3 +/- 1.8%, 13.5 +/- 0.7% and 13.5 +/- 2.0%, respectively). Kasumi-1 AML tells exhibited a reduced DSB repair capacity compared to AG10107 and GM03715 normal lymphocytes as well as CEM acute T-cell lymphoblastic leukaemia cells (6.4 +/- 0.8% vs. 10.8 +/- 0.7%, 27.3 +/- 1.1% and 20.5 +/- 1.6%, respectively). The modified HCR assay can be used for functional DNA repair analysis in living cells of patients with pre- and post-leukaemic conditions as well as in leukaemic blasts to elucidate the role of DNA repair in de novo and t-AML leukaemogenesis and to determine the individual susceptibility to t-AML prior to chemotherapy. PMID- 17852815 TI - Association between nitric oxide and oxidative stress in continuous ambulatory peritoneal dialysis patients with peritonitis. AB - BACKGROUND: Peritonitis is a major complication in continuous ambulatory peritoneal dialysis (CAPD) patients, and the mechanisms involved in the pathology are important if the success rate of treatment strategies is to increase. MATERIAL AND METHODS: A total of 50 CAPD patients (25 with 25 episodes of peritonitis and 25 with no clinical or laboratory signs of infection) were included in the study. Malondialdehyde (MDA) and nitric oxide (NO) metabolites in serum and dialysate effluents were determined. RESULTS: The dialysate/serum (D/S) ratio of the NO metabolites and serum NO metabolite concentrations were significantly higher in the peritonitis group. Serum and dialysate MDA concentrations were also significantly higher in the peritonitis group. The D/S ratio of MDA was significantly higher in the control group. CONCLUSIONS: Local peritoneal NO production and oxidative stress seem to increase in CAPD patients during the peritonitis attack. PMID- 17852816 TI - Angiotensin-converting enzyme gene polymorphism and coronary reactivity in young men. AB - The purpose of the study was to examine whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene affects the vasodilatory properties of coronary arteries in healthy men. The ACE genotypes of 128 men (mean age 35 +/- 4 years) were determined and related to myocardial blood flow. The blood flow was measured by positron emission tomography at rest and during vasodilation caused by adenosine or dipyridamole infusion. The coronary flows and resistances at rest and during stimulation with adenosine or dipyridamole did not differ between the ACE genotypes. Furthermore, this polymorphism had no effect on coronary flow reserve corrected by a rate-pressure product. In conclusion, the ACE I/D polymorphism does not seem to affect myocardial reactivity--an early indicator of atherosclerosis--in healthy subjects. PMID- 17852817 TI - Age-dependent biochemical quantities: an approach for calculating reference intervals. AB - OBJECTIVE: A parametric method is often preferred when calculating reference intervals for biochemical quantities, as non-parametric methods are less efficient and require more observations/study subjects. Parametric methods are complicated, however, because of three commonly encountered features. First, biochemical quantities seldom display a Gaussian distribution, and there must either be a transformation procedure to obtain such a distribution or a more complex distribution has to be used. Second, biochemical quantities are often dependent on a continuous covariate, exemplified by rising serum concentrations of MUC1 (episialin, CA15.3) with increasing age. Third, outliers often exert substantial influence on parametric estimations and therefore need to be excluded before calculations are made. MATERIAL AND METHODS: The International Federation of Clinical Chemistry (IFCC) currently recommends that confidence intervals be calculated for the reference centiles obtained. However, common statistical packages allowing for the adjustment of a continuous covariate do not make this calculation. RESULTS: In the method described in the current study, Tukey's fence is used to eliminate outliers and two-stage transformations (modulus-exponential normal) in order to render Gaussian distributions. Fractional polynomials are employed to model functions for mean and standard deviations dependent on a covariate, and the model is selected by maximum likelihood. Confidence intervals are calculated for the fitted centiles by combining parameter estimation and sampling uncertainties. Finally, the elimination of outliers was made dependent on covariates by reiteration. CONCLUSIONS: Though a good knowledge of statistical theory is needed when performing the analysis, the current method is rewarding because the results are of practical use in patient care. PMID- 17852818 TI - The association of HDL cholesterol concentration with the -629C>A CETP promoter polymorphism is not fully explained by its relationship with plasma cholesteryl ester transfer. AB - OBJECTIVE: HDL cholesterol is associated with the -629C>A cholesteryl ester transfer protein (CETP) promoter polymorphism. This relationship may in part be explained via effects on plasma cholesteryl ester transfer (CET), which reflects the activity of CETP in the context of endogenous lipoproteins, but also via CET independent pathways involved in HDL metabolism. In this study, we determined the contributions of the CETP -629 C>A genotype, plasma CETP mass and cholesteryl ester transfer to HDL cholesterol. MATERIAL AND METHODS: The -629 C>A CETP gene promoter polymorphism, plasma CETP mass, CET, HDL cholesterol, lipids and apolipoprotein (apo) A-I were measured in 220 non-diabetic men without cardiovascular disease. RESULTS: Plasma CETP mass (p<0.001) and CET (p<0.001) were higher, whereas HDL cholesterol (p<0.05) and plasma apo A-I levels (p<0.05) were lower in CC compared to AA carriers. Univariate regression analysis showed that plasma CET was related to the CETP genotype (p = 0.004), plasma CETP mass (p<0.001) and triglycerides (p<0.001). In a multiple linear regression model, HDL cholesterol was related to CETP genotype (p = 0.04) and plasma triglycerides (p<0.001) without independent contributions of plasma CETP mass and CET (p>0.20 for both). CONCLUSIONS: This study suggests that, despite a relationship between a common CETP gene variation and plasma cholesteryl ester transfer, the association between CETP gene and HDL cholesterol appears to be at least in part unexplained by the plasma cholesteryl ester transfer process. PMID- 17852819 TI - Body weight and oral contraceptives are the most important modulators of serum CRP levels. AB - BACKGROUND: C-reactive protein (CRP) levels are modulated by endogenous and exogenous factors independently of inflammation. The present study investigated the impact of oral contraceptives, endogenous oestrogens, age, gender, smoking, body mass index (BMI) and lipid levels on CRP concentrations in a healthy collective. METHODS: Highly sensitive CRP, total cholesterol, HDL-cholesterol and LDL-cholesterol levels were measured in 850 blood donors (438 M, 412 F); 227 women in this group used oral contraceptive formulations (OC). Additionally, serum samples from 58 women undergoing in vitro fertilization cycles (IVF) were tested for CRP. Results. The 97.5th percentile of CRP levels of the blood donors was 4.91 mg/L in men, 7.52 mg/L in OC non-users and 11.95 mg/L in OC users. Overweight gives a 2-fold increase of median CRP levels in men and women. The combination of overweight and OC use in women resulted in 6-fold median CRP levels. Age, smoking and lipid levels were influencing factors of lower significance. In IVF patients the elevated oestradiol levels had no influence on CRP concentrations in multivariance analysis. CONCLUSION: The diagnostic and predictive value of CRP levels is most affected by BMI and oral contraceptive use, which suggests the need for further investigations into the role of CRP modulating factors in monitoring infectious diseases. PMID- 17852820 TI - Pleural fluid ADA, IgA-ELISA and PCR sensitivities for the diagnosis of pleural tuberculosis. AB - The diagnosis of pleural tuberculosis (pTB) is difficult, and more sensitive and specific techniques are needed. In the period August 1998 to November 2002, we evaluated 132 patients with a pleural effusion submitted to a thoracentesis and pleural biopsy in a tertiary care hospital in Rio de Janeiro, Brazil. Three tests were performed and compared in the pleural fluid: ADA activity measurement, IgA ELISA for two combined specific Mycobacterium tuberculosis antigens, and polymerase chain reaction (PCR) for detection of M. tuberculosis DNA. Ninety-five patients (72%) were given a final diagnosis of pTB. Overall histopathologic sensitivity was 77%. The sensitivities of pleural fluid culture and AFB smear were 42% and 1%, respectively. Twenty-one (22%) additional patients had a clinical diagnosis of pTB. Median follow-up time of all TB patients after the completion of antituberculous treatment was 13 months. Sensitivities of ADA, IgA ELISA and PCR were 91%, 78% and 82%, while specificities were 93%, 96% and 85%, respectively. Only ADA sensitivity was significantly higher than the histopathologic examination (McNemar chi2 test; p = 0.002) and also significantly higher than ELISA (p = 0.049), but not higher than PCR (p = 0.143). We conclude that the routine use of ADA activity measurement in pleural fluid can obviate the need for a pleural biopsy in the initial diagnostic approach to pleural effusions, while IgA-ELISA and PCR techniques, potentially more specific tests, need further refinement to improve their accuracy. PMID- 17852821 TI - Biexponential model for the kinetics of the substitution reaction in the radioimmunoassay of triiodothyronine. AB - The influence of initial concentrations, ionic strength, viscosity and temperature on the substitution reaction of 125I-triiodothyronine (T3) (M) by unlabelled T3 (Q) in the immunocomplex PM (P = anti-T3 antibody) has been studied, and a kinetic model is proposed. The apparent rate constant is dependent on the initial concentration of labelled and unlabelled T3, viscosity and temperature, and independent of ionic strength. The reaction is endothermic and is not controlled by diffusion. The results obtained are in line with the proposed model. We propose some modifications for optimizing the technique. PMID- 17852822 TI - Health-associated reference values for arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) measured with high-performance liquid chromatography. AB - OBJECTIVE: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide production. It has been implicated in various pathological processes, especially processes involving the cardiovascular system. Plasma concentration of ADMA (p-ADMA) has been measured in several studies with different techniques, and a wide range of normal values has been published. With use of high performance liquid chromatography (HPLC) with fluorescence detection, we have established health-associated reference values for p-ADMA, p-arginine, p SDMA and the p-arginine/p-ADMA and p-arginine/p-SDMA ratios. MATERIAL AND METHODS: Blood samples were taken from 238 blood donors (112 F and 126 M). HPLC was used to analyse arginine, ADMA and SDMA. Reference values are presented as 2.5 and 97.5 percentiles estimated by the bootstrap method. RESULTS: The reference interval for p-ADMA is 0.40-0.77 micromol/L for the whole population, 0.41-0.79 micromol/L for men, 0.38-0.73 micromol/L for women 45 years or less, and 0.41-0.84 micromol/L for women >45 years. CONCLUSIONS: Age affects p-ADMA in healthy women, but not in men. PMID- 17852823 TI - Dramatic reduction of erythrocyte glucose-6-phosphate dehydrogenase activity in athletes participating in the ultradistance foot race "Spartathlon". AB - OBJECTIVE: To investigate the effect of a long-distance endurance exercise "Spartathlon" on erythrocyte glucose-6-phosphate dehydrogenase (G(6)PD) activity. MATERIAL AND METHODS: The study comprised 15 male runners, median age 36.5 years. Blood samples were obtained in the 15 min before the race and again within 15 min after the end of the race. Erythrocyte glutathione (GSH and GSSG) and plasma malonyldialdehyde were measured with HPLC methods, and total antioxidant capacity (TAC), total hyperoxides and G(6)PD activity with commercial kits. Lipids, uric acid and total bilirubin were determined with a clinical chemistry analyser. RESULTS: Total hyperoxides were found statistically reduced, whereas total bilirubin was measured elevated post-race. Interestingly, GSSG levels were found increased (167.3+/-12.0 versus 219.5+/-20.3 micromol/L; p<0.005) as well as GSSG/GSH ratio (16.0+/-1.3 versus 20.60+/-1.65; p<0.05) post-race. In contrast, G(6)PD activity was found remarkably decreased (8.72+/-3.10 versus 3.8+/-2.5 U/g Hb; p<0.0001) pre versus post the event. CONCLUSION: Red blood cell G(6)PD activity in athletes may be reduced post-race as a consequence of the modulation of NADP/NADPH levels and elevation of the erythrocyte GSSG, and especially GSSG/GSH ratio, resulting in an impairment of the hexose monophosphate shunt. PMID- 17852824 TI - Performance of automated measurement of antibodies to cyclic citrullinated peptide in the routine clinical laboratory. AB - OBJECTIVE: To evaluate the performing technical and clinical characteristics of an automated system for routine measurement of anticyclic citrullinated peptide antibodies (aCCP), a new marker for rheumatoid arthritis (RA). MATERIAL AND METHODS: Reproducibility, repeatability and linearity of aCCP, as measured by an automated fluorescent enzyme immunoassay (FEIA/Phadia), were evaluated and compared with the performance of a manual ELISA technique (Axis Shield Diagnostics). Clinical verification of both methods included estimation of sensitivity in RA patients (n = 42) and specificity in well-characterized non-RA autoimmune disease controls (n = 49) and healthy subjects (n = 39). RESULTS: Precision studies showed a coefficient of variation between 4.9 % and 10 % for the FEIA technique and between 6.35% and 19% for the ELISA technique. Both systems showed good linear response. Sensitivity of aCCP for RA was 74% for FEIA and 79% for ELISA. Specificity was 100% for both methods, as calculated for healthy subjects. For non-RA-diseased controls, specificities of 98% and 94% were obtained for FEIA and ELISA, respectively. Both methods were concordant in 97% of cases. Increasing the cut-off for the ELISA system from >5 U/mL to >11 U/mL resulted in lower sensitivity (71.4%) but higher specificity (98.0%), i.e. improved discriminating power between RA and non-RA and 100% agreement between both methods. CONCLUSION: Automated FEIA measurement of aCCP in the routine clinical laboratory improves imprecision compared to the manual ELISA. Our preliminary results suggest that an increase in cut-off for the ELISA can improve specificity to RA from 94% to 98 %. PMID- 17852825 TI - Q-T interval (QT(C)) in patients with cirrhosis: relation to vasoactive peptides and heart rate. AB - OBJECTIVE: Prolonged Q-T interval (QT) has been reported in patients with cirrhosis who also exhibit profound abnormalities in vasoactive peptides and often present with elevated heart rate (HR). The aim of this study was to relate QT to the circulating level of endothelins (ET-1 and ET-3) and calcitonin gene related peptide (CGRP) in patients with cirrhosis. In addition, we studied problems with HR correction of QT. MATERIAL AND METHODS: Forty-eight patients with cirrhosis and portal hypertension were studied during a haemodynamic investigation. Circulating levels of ETs and CGRP were determined by radioimmunoassays. Correction of QT for HR above 60 beats per min was performed using the methods described by Bazett (QT(C)) and Fridericia (QT(F)). RESULTS: Prolonged QT(C) (above 440 ms), found in 56% of the patients, was related to the presence of significant portal hypertension and liver dysfunction (p < 0.05 to 0.001), but not to elevated ET-1, ET-3 or CGRP. When corrected according to Bazett, QT(C) showed no significant relation to differences in HR between patients (r = 0.07, ns). QTF showed some undercorrection of HR (r = -0.36; p < 0.02). During HR variation in the individual patient, QT(C) revealed a small but significant overcorrection (2.6 ms per heartbeat per min; p < 0.001). This value was significantly (p < 0.02) smaller with QTF (1.2 ms per heartbeat per min). CONCLUSIONS: The prolonged QT(C) in cirrhosis is related to liver dysfunction and the presence of portal hypertension, but not to the elevated powerful vasoconstrictor (ET-1) or vasodilator (CGRP, ET-3) peptides. The problems with correction of the QT for elevated HR in cirrhosis are complex, and the lowest HR should be applied for determination of the QT. PMID- 17852826 TI - Biological variation and reference intervals for circulating osteopontin, osteoprotegerin, total soluble receptor activator of nuclear factor kappa B ligand and high-sensitivity C-reactive protein. AB - OBJECTIVE: Monitoring inflammatory diseases and osteoclastogenesis with osteopontin (OPN), osteoprotegerin (OPG), total soluble receptor activator of nuclear factor kappa B ligand (total sRANKL) and high-sensitivity C-reactive protein (hsCRP) has recently attracted increased interest. The purpose of our study was to determine reference intervals, variability caused by sampling time, biological variation and stability after repeated freeze-thaw cycles of circulating levels of OPN, OPG, total sRANKL and hsCRP. MATERIAL AND METHODS: Plasma OPN and plasma OPG concentrations were determined with sandwich ELISA; serum total sRANKL concentration was determined using a two-site sandwich ELISA; and hsCRP was analysed by turbidimetry in 300 Danish blood donors (183 M and 117 F) with a median age of 43 years (range 18-64 years). Variability due to biological variation and sampling time was studied in serial samples from 38 healthy subjects. RESULTS: The 95th percentiles in the donors were 76 microg/L for OPN, 4.2 pmol/L for OPG, 40.2 nmol/L for total sRANKL and 12 mg/L for hsCRP. The overall medians for both genders were 51 microg/L, 2.2 pmol/L, 0.66 nmol/L and 1.0 mg/L, respectively. We found a significant correlation between hsCRP and OPN (rho = 0.173; p<0.003). The biological within-subject variations were calculated to be 8.2 % for OPN, 8.8% for total sRANKL and 50% for hsCRP. CONCLUSIONS: Reference intervals have been established with a high analytic performance for OPN and an acceptable analytic performance for OPG and total sRANKL. The study revealed low biological variation for OPN and total sRANKL and high biological variation for hsCRP. PMID- 17852827 TI - Improvement of myocardial blood flow by lipid-lowering therapy with pravastatin is modulated by apolipoprotein E genotype. AB - OBJECTIVE: Apolipoprotein E (apoE) polymorphism affects the risk of advanced coronary artery disease, but its role in early atherosclerosis remains unknown. We used positron emission tomography (PET) to study whether coronary reactivity or its response to pravastatin is related to the apoE genotype. MATERIAL AND METHODS: Samples from 44 mildly hypercholesterolaemic men (aged 35 +/- 4 years) of an earlier trial were re-analysed according to apoE genotype. Subjects were randomized to receive either 40 mg/day pravastatin or placebo for 6 months. To assess coronary reactivity, myocardial blood flow was measured by PET at rest and during adenosine infusion. PET studies and lipid analyses were done at baseline and after 6 months of therapy. RESULTS: There were no differences between apoE epsilon3/3 and epsilon4/3 genotypes in basal or adenosine-stimulated flow or in coronary flow reserve (CFR) at baseline. There was a significant apoE genotype-by treatment group interaction regarding the change in adenosine-stimulated flow (ANCOVA; p = 0.018) and CFR (p = 0.020) at the end of the study. In the pravastatin group, the adenosine-stimulated flow increased by 32.5 % in subjects with epsilon3/3 (n = 9), but decreased non-significantly (-14.4 %) in subjects with epsilon4/3 (n = 9) (p = 0.0009). The corresponding changes in CFR were +17.8 % for epsilon3/3 and (-11.9 % for epsilon4/3 (p = 0.05). There were no significant changes from the baseline values in placebo recipients. After pravastatin treatment, both genotype groups showed a similar decrease in serum total and low-density lipoprotein cholesterol (p<0.0001 for both). CONCLUSIONS: Coronary function improves by 6 months of pravastatin in subjects with the apoE epsilon3/3 genotype, but not in those with the epsilon4/3. PMID- 17852828 TI - High expression of CD7 on CD34+ cells is not linked to deletion of derivative chromosome 9 or lack of dendritic cells in chronic myeloid leukaemia. AB - OBJECTIVE: High expression of CD7 on CD34+ cells (>20 %) has been shown to be associated with inferior prognosis in chronic myeloid leukaemia (CML), but the reason has not been unravelled. We set out to investigate whether lack of dendritic cells or der(9)t(9;22)(q34;q11) deletions might be correlated with increased CD7 expression on CD34+ cells in CML. MATERIAL AND METHODS: We identified 43 patients in our cohort of CML patients in the first chronic phase in whom we were able to assess the expression of CD7 on CD34+ cells. der(9)t(9;22) deletions were evaluated by FISH (fluorescent in situ hybridization) analyses and the proportions of plasmacytoid and myeloid dendritic cells were assessed by flow cytometry. RESULTS: High and low expressions of CD7 on CD34+ cells were found in 19 and 24 patients, respectively. Two out of 20 patients examined had a der(9)t(9;22)(q34;11) deletion, one patient with high expression and one with low expression of CD7 on CD34+ cells. The proportions of plasmacytoid dendritic cells (PDCs) and myeloid dendritic cells (MDCs) were reduced in a majority of patients in our cohort, but no correlation was found between high or low expression of CD7 on CD34+ cells and the proportion of dendritic cells. CONCLUSIONS: A high proportion of CD34+CD7+ cells in patients with CML is not associated with der(9)t(9;22)(q34;q11) deletions. Nor did we find any correlation between CD7 expression on CD34+ cells and lack of dendritic cells. High expressions of CD7 on CD34+ cells and der(9)t(9;22)(q34;q11) deletions seem to be independent prognostic markers in CML. PMID- 17852829 TI - Comparison of different culture conditions for human mesenchymal stromal cells for clinical stem cell therapy. AB - OBJECTIVE: Mesenchymal stromal cells (MSCs) from adult bone marrow (BM) are considered potential candidates for therapeutic neovascularization in cardiovascular disease. When implementing results from animal trials in clinical treatment, it is essential to isolate and expand the MSCs under conditions following good manufacturing practice (GMP). The aims of the study were first to establish culture conditions following GMP quality demands for human MSC expansion and differentiation for use in clinical trials, and second to compare these MSCs with MSCs derived from culture in four media commonly used for MSC cultivation in animal studies simulating clinical stem cell therapy. MATERIAL AND METHODS: Human mononuclear cells (MNCs) were isolated from BM aspirates by density gradient centrifugation and cultivated in a GMP-accepted medium (EMEA medium) or in one of four other media. RESULTS: FACS analysis showed that the plastic-adherent MSCs cultured in EMEA medium or in the other four media were identically negative for the haematopoietic surface markers CD45 and CD34 and positive for CD105, CD73, CD90, CD166 and CD13, which in combined expression is characteristic of MSCs. MSC stimulation with vascular endothelial growth factor (VEGF) increased expression of the characteristic endothelial genes KDR and von Willebrand factor; the von Willebrand factor and CD31 at protein level as well as the capacity to develop capillary-like structures. CONCLUSIONS: We established culture conditions with a GMP compliant medium for MSC cultivation, expansion and differentiation. The expanded and differentiated MSCs can be used in autologous mesenchymal stromal cell therapy in patients with ischaemic heart disease. PMID- 17852830 TI - Elevated serum erythropoietin concentration is associated with coordinated changes in red blood cell and reticulocyte indices of pregnant women at term. AB - The aim of this study was to evaluate the relationship between the erythropoietin (EPO) concentration and both the advanced cellular indices reflecting the haemoglobin contents of red blood cells and reticulocytes and the serum markers of iron status. The study population comprised pregnant women at term (n = 210). The serum EPO, transferrin receptor (TfR), ferritin, the percentages of hypochromic red blood cells (%HYPOm) or reticulocytes (%HYPOr) and the cellular haemoglobin in mature red blood cells (CHm) or in reticulocytes (CHr) were measured in maternal blood before delivery. The EPO concentration was elevated above the reference limit (>31.5 mIU/mL) in 16 % of all pregnant women, and appeared to correlate in a linear fashion, especially with %HYPOm (r = 0.52, p<0.001), %HYPOr (r = 0.57, p<0.001) and CHr (r = -0.45, p<0.001). The significant (p<0.05) predictors of EPO in the multivariate stepwise regression analysis were %HYPOr, Hb, %HYPOm and MCV. In general, the lower the cellular haemoglobin content, the higher the overall maternal EPO production. In conclusion, elevated %HYPOm and %HYPOr reflecting iron-deficient erythropoiesis are associated with an increase in EPO concentration in maternal blood. This could be explained by subclinical iron deficiency being accompanied by a compensatory EPO response. PMID- 17852831 TI - Genotyping of the reduced folate carrier-1 c.80G>A polymorphism by pyrosequencing technology: importance of PCR and pre-PCR optimization. AB - When developing a genotyping assay by Pyrosequencing(trade mark) technology for the RFC1 (SLC19A1) c.80G>A polymorphism (rs1051266), unequal peak heights in the pyrograms were observed, probably due to unequal amplification of the mutated and wild-type alleles. This rarely occurring problem could potentially render assignment of heterozygous genotypes uncertain. When the PCR conditions were studied, it was found that substitution of the dGTP nucleotide in the master mix by dGTP and dITP in proportion 1:1 largely overcame this problem. Heat denaturation of the DNA at 95 degrees C before PCR also counteracted the problem. A combination of these two modifications of the standard pyrosequencing PCR protocol gave the best results. We conclude that, with these modifications, the RFC1 c.80G>A SNP can be reliably assayed by pyrosequencing. PMID- 17852832 TI - Decreased serum endoglin level in patients with amyotrophic lateral sclerosis: a preliminary report. AB - OBJECTIVES: Angiogenic mechanisms may have a role to play in the neurodegeneration observed in amyotrophic lateral sclerosis (ALS). The aim of the present study was to measure serum angiogenic factor endoglin (ENG) levels in patients with ALS. MATERIAL AND METHODS: The study involved 25 ALS patients and 25 controls. Concentrations of ENG in serum samples were measured using a human Endoglin/CD105 ELISA kit (R&D Systems, Minneapolis, Minn., USA). RESULTS: Serum ENG concentrations were 14 % lower in the patients with ALS compared to controls (4.57 versus 3.97 ng/mL; p<0.05). There was no significant difference in serum ENG levels between subgroups of patients with ALS subdivided depending on clinical state, type of ALS onset and duration of the disease (p>0.05). The correlation between serum ENG levels and clinical parameters of ALS was not significant either (p>0.05). CONCLUSIONS: Results indicate that ENG may be implicated in the pathomechanism of ALS. A decrease in ENG levels, as observed in this study, may accelerate neurodegeneration of motor neurons in ALS through chronic ischaemia caused by impaired perfusion. PMID- 17852833 TI - Post-ischaemic restituted intestinal mucosa is more resistant to further ischaemia than normal mucosa in the pig. AB - OBJECTIVE: Ischaemic preconditioning may protect the intestine from subsequent prolonged ischaemia. This study evaluates whether a much longer initial ischaemia, encountered clinically, may modify intestinal resistance to further ischaemia in a pig model. MATERIAL AND METHODS: After cross-clamping of the superior mesenteric artery for 1 h, the intestine was either reperfused for 8 h or a second cross-clamping for 1 h was performed at 4 h of reperfusion. Based on microarray analysis of intestinal samples at 1, 4 and 8 h of reperfusion, mRNA of selected genes was measured with QRT-PCR. RESULTS: The first ischaemic period caused exfoliation of surface epithelial cells from the basement membrane comprising about 90 % of the villi tips, a marked increase in permeability and depletion of ATP. The second ischaemic challenge caused about 30 % less denudation of the basement membrane (p = 0.008), no increase in permeability (p = 0.008) and less depletion of ATP (p = 0.039). mRNAs for superoxide dismutase 2, heat shock proteins and signal transducer and activator of transcription 3, which may protect against ischaemia/reperfusion injury, were up-regulated throughout the reperfusion period. mRNAs for matrix metalloproteinase 1, connexin 43 and peripheral myelin 22, which may be associated with cell migration or tight junctions, showed a particular up-regulation at 4 h of reperfusion. CONCLUSION: One hour of initial ischaemia followed by 4 h of reperfusion is associated with increased intestinal resistance to further ischaemia. The differential regulation of genes identified in this study provides working hypotheses for mechanisms behind this observation. PMID- 17852834 TI - Fecal calprotectin: assessment of a rapid test. AB - BACKGROUND: Calprotectin, a protein found mainly in neutrophil granulocytes, is used as an inflammatory marker, while the fecal concentration of the protein is used to detect gastrointestinal (GI) inflammation. MATERIAL AND METHODS: Fecal calprotectin in 100 stool samples was measured by the ELISA method and by a new rapid test. Eighty-two patients had fecal calprotectin measured for clinical reasons and delivered 95 stool samples. The rest were delivered by healthy volunteers. RESULTS: The association between the two tests was statistically significant (p<0.0001, chi(2) test). With calprotectin values <15 microg/g, the sensitivity and specificity of the new rapid test was 96 % (95 % confidence interval (CI), 87-100 %) and 70 % (CI, 55-83 %), respectively, with a negative predictive value of 94 % (CI, 81-99 %). With values >15 microg/g, the rapid test was less accurate, thus rendering results in this range difficult to interpret. CONCLUSIONS: The new rapid test is useful as a screening test for excluding GI inflammation when the cut-off of 15 microg/g is used. With fecal calprotectin concentrations >15 microg/g, the rapid test should be supplemented by quantitative measurement. PMID- 17852835 TI - Regulation of desaturase expression in HL60 cells. AB - The expression of delta 5 desaturase (D5D), delta 6 desaturase (D6D) and delta 9 desaturase (D9D) was determined by RT-PCR in the human promyelocytic cell line HL60. During 72 h of culture with 10% FBS, D5D and D6D were upregulated 5 to 6 fold, whereas D9D approximately doubled. The addition of fatty acids (FAs) to the culture medium suppressed upregulation of all desaturases. N-3 and n-6 FA appeared to be more effective than n-9 or saturated FA. When FAs were added after 72 h, further upregulation during the next 24 h was suppressed for nearly all desaturases and FAs tested, except for D5D when oleic acid (OA) or stearic acid (SA) was added. In cells cultured with restricted amounts of FBS, desaturase expression increased with decreasing concentrations of FBS. Cellular FA content decreased by 60% in the neutral lipid fraction, whereas that of the phospholipid fraction decreased by 10% during 72 h of culture. The largest decrease occurred in the sum of n-3 and n-6 FA of the neutral lipid fraction, which was reduced by 83%, whereas the content of these FAs in the phospholipid fraction decreased by 32%. The results indicate that when the supply of FA to HL60 cells is limited, the intracellular content of n-3 and n-6 FA decreases and this leads to upregulation of the desaturases, particularly D5D and D6D. Since HL60 cells resemble human leukocytes, the results suggest that desaturase expression in leukocytes may be exploited as a biomarker for FA status. PMID- 17852836 TI - Butyrylcholinesterase K variants increase the risk of coronary artery disease in the population of western Iran. AB - The conflicting results of several studies suggest that there is an association between the butyrylcholinesterase-K variant (BCHE-K, G1615A/Ala539Thr) and the risk of developing coronary artery disease (CAD) in diabetes and non-diabetic subjects. The objective of this study was to determine whether the presence of the BCHE-K variant exacerbates the risk of CAD in patients from western Iran with and without type 2 diabetes mellitus (T2DM). This case-control study comprised 464 subjects undergoing their first coronary angiography. They were matched and randomly assigned into four groups: CAD+T2DM+ (CAD/T2DM), CAD+DM(-) (CAD/ND), CAD(-)DM+ (T2DM/NCAD) and CAD(-)DM(-)(control). The BCHE-K variant was detected by PCR-RFLP. The BCHE-K allele frequency in CAD patients with and without T2DM [total CAD (TCAD)] and separately for each group (CAD/T2DM and CAD/ND) was significantly higher than in the control group (21.1 % versus 13.3 % (p = 0.001), 22.4 % versus 13.3 % (p = 0.001) and 19.7 % versus 13.3 % (p = 0.015), respectively). The odds ratios (ORs) for the BCHE-K heterozygous and homozygous variants in TCAD subjects were 1.65 (95 % CI 1.17-2.3; p = 0.004) and 4.3 (1.05 19.4; p = 0.048); for CAD/T2DM individuals 1.76 (1.2-2.6; p = 0.004) and 4.73 (0.96-23.3; p = 0.052); and for CAD/ND patients 1.53 (1.05-2.3; p = 0.029) and 3.88 (0.8-19.7; p = 0.7), respectively. The OR of the BCHE-K allele was found to be 1.74 (1.1-2.4; p = 0.001) in TCAD subjects, 1.87 (1.12-1.48; p = 0.001) in the CAD/T2DM group and 1.59 (1.04-1.4; p = 0.016) in CAD/ND subjects. These data suggest that the BCHE-K allele increases the risk of CAD in the population (with and without DM) in western parts of Iran, and its presence intensifies the risk of CAD in T2DM. The fact that the BCHE-K allele, even in the heterozygous form, exacerbates the risk of CAD in this population, suggests that a specific therapeutic intervention should be considered for this particular group of patients. PMID- 17852837 TI - Telmisartan-enhanced hypercholesterolaemic serum-induced vascular endothelial growth factor expression in immortalized human umbilical vascular endothelial cells. AB - OBJECTIVE: To clarify whether hypercholesterolaemia can increase vascular endothelial growth factor (VEGF) expression in human umbilical vascular endothelial cells (HUVECs) through the phosphatidylinositol 3-kinase (PI3K) pathway, and whether a special angiotensin II receptor blocker, telmisartan, can attenuate VEGF expression induced by hypercholesterolaemia. METHODS: Levels of VEGF expression, PI3K activity and angiogenesis in vitro were determined by various methods after HUVECs were incubated with hypercholesterolaemic serum or combined with telmisartan and/or wortmannin. RESULTS: We found that hypercholesterolaemic serum (cholesterol > or = 0.08 mmol/L) can increase VEGF expression in HUVECs and that telmisartan cooperates with hypercholesterolaemic serum in promoting VEGF expression. The increased VEGF expression was associated with enhanced PI3K activity and could be significantly inhibited by wortmannin, a potent PI3K inhibitor. Likewise, hypercholesterolaemic serum significantly promoted angiogenesis in vitro, which could be inhibited when PI3K activity was suppressed. CONCLUSIONS: Our study suggests that hypercholesterolaemic serum induces VEGF expression through PI3K in HUVECs and that telmisartan cooperates with hypercholesterolaemia in promoting VEGF expression. PMID- 17852838 TI - Patient-centred care--preanalytical factors demand attention: a questionnaire study of venous blood sampling and specimen handling. AB - OBJECTIVE: Most mistakes in laboratory medicine are the result of human error occurring before the blood sample reaches the laboratory. This survey of preanalytical procedures was designed to identify sources of error and potential targets for quality improvement strategies. MATERIAL AND METHODS: The staff in a highly specialized surgical ward at a university hospital completed a questionnaire addressing the collection and handling of venous blood samples in plastic vacuum test-tubes for general clinical chemistry testing. RESULTS: The results suggest that venous blood sampling instructions are not always followed. When uncertain about how a sample should be collected, the majority of respondents rely on potentially poor sources of information, such as out-of-date printed instructions or the advice of a colleague, rather than consult up-to-date electronic instructions. Furthermore, they do not always report errors and the referrals are not always handled according to sampling instructions. The respondents were highly motivated, however, and had a strong interest in receiving further education in, and assuming increased responsibility for, venous blood sampling procedures in the ward. CONCLUSIONS: We believe that the introduction of standardized routines and regular staff training, combined with an exchange of the existing paper-based referral management system with an electronic system for managing referrals, could increase safety in the preanalytical process, with positive effects on patient safety. Given the importance of venous blood samples in patient care, a more extensive study covering other hospital wards and primary health-care centres is needed. PMID- 17852839 TI - Incidence rates and causes of cirrhosis in a Norwegian population. AB - OBJECTIVE: To investigate the incidence rate and causes of cirrhosis in a Norwegian population. We also sought to assess the degree of underreporting of cirrhosis to the Norwegian Death Registry. MATERIAL AND METHODS: All 1264 patients treated at Aker University Hospital in the period January 1999 to March 2004 who were given a diagnosis indicating cirrhosis, chronic liver disease or symptoms possibly attributable to cirrhosis were screened retrospectively. A search in the registry of histological diagnoses at Department of Pathology was also carried out. Based on the results of histological examinations and non histological criteria, cirrhosis was confirmed in 194 patients. Calculations of the incidence rate of cirrhosis and frequencies of the various etiologies were based on 93 patients living in the catchment area of the hospital. Causes of death were retrieved from the Norwegian Death Registry. RESULTS: The incidence rate of cirrhosis was 134 per million per year. The majority of cases were due to alcoholic liver disease (53%), followed by viral liver disease (12%), various autoimmune liver diseases (12%), hemochromatosis (4%) and non-alcoholic steatohepatitis (NASH) (3%). No etiology was established in 16%, a group with a high prevalence of diabetes mellitus, indicating that some of these cases were possibly caused by NASH. Among 105 deaths in this cohort of 194 cirrhotic patients, the diagnosis of cirrhosis was absent in the Norwegian Death Registry in 30% of cases. CONCLUSIONS: The incidence of cirrhosis in Norway is relatively low, with alcohol as the most important etiologic factor. Significant underreporting to the Norwegian Death Registry was observed. PMID- 17852840 TI - Mutations in CARD15 and smoking confer susceptibility to Crohn's disease in the Danish population. AB - OBJECTIVE: Three CAspase Recruitment Domain (CARD15) mutations have shown to predispose to Crohn's disease in Caucasian populations. The aim of this study was to investigate the mutation frequency in patients with inflammatory bowel disease and in healthy controls in Denmark. MATERIAL AND METHODS: Genotyping of the three common CARD15 mutations was carried out on 388 patients with Crohn's disease, 565 patients with ulcerative colitis and 796 healthy controls using real-time PCR. Allele and genotype frequencies in the three groups were compared. A possible additive effect of smoking on CARD15 mutations was also examined. RESULTS: Carrying at least one CARD15 mutation was significantly more common in patients with Crohn's disease compared with healthy controls (21% versus 10%; p <0.001). A gene-dosage effect was observed (ORadj.smoking 22.2; p <0.001 for carrying two CARD15 mutations versus ORadj.smoking 1.8; p=0.01 for carrying one CARD15 mutation). The 1007insC protein truncating mutation was the major contributing mutation. Ileal involvement was more common in Crohn's disease patients with CARD15 mutations as opposed to patients without CARD15 mutations (ORadj.smoking 3.6; p <0.001). Smoking was independently associated with Crohn's disease (OR 1.8; p <0.001), but no multiplicative effect of smoking on CARD15 genotypes was found. CONCLUSIONS: In the Danish population, CARD15 mutations were found to be associated with Crohn's disease, hence supporting the hypothesis of a genetic component contributing to the disease. Further research for other genes possibly involved in Crohn's disease may result in the use of genetic testing for diagnosis or treatment of Crohn's disease in the future. PMID- 17852841 TI - Gastrointestinal symptoms are associated with hypothalamic-pituitary-adrenal axis suppression in healthy individuals. AB - OBJECTIVE: The brain-gut axis has been proposed to influence symptoms in irritable bowel syndrome (IBS). In animal studies corticotropin-releasing hormone (CRH) challenge has been associated with decreased upper gastrointestinal motility and increased colonic motility. The purpose of this study was to investigate the association between gastrointestinal symptoms and the effect of CRH on the hypothalamic-pituitary-adrenal (HPA) axis using a weight-adjusted low dose dexamethasone test in a group of healthy individuals (n = 157). MATERIAL AND METHODS: Pre- and post-dexamethasone morning serum cortisol was analysed. All participants completed questionnaires regarding symptoms of IBS (GSRS-IBS (Gastrointestinal Symptom Rating Scale-IBS) and symptoms of anxiety and depression (HADS (Hospital Anxiety and Depression Scale)). After exclusions, 124 subjects were available for analysis (F/M: 60/64, mean age 55.8 years, SD 15.4, range 21-80 years). RESULTS: A positive correlation was found between the GSRS IBS score and HADS score (rs =0.36; p <0.001). There was no linear correlation between either pre- (rs = 0.145; p = 0.11) or post-dexamethasone cortisol levels (rs =0.087; p =0.337) and GSRS-IBS scores. By subgrouping the subjects at the lower and higher 25th percentiles of their post-dexamethasone morning cortisol levels, we found a trend towards a higher GSRS-IBS score (median 7.0 versus 5.0; p =0.069) (multivariate adjusted OR 2.6; CI 0.80-8.3) and a significantly higher diarrhoea score (median 2 versus 0; p = 0.021) (multivariate adjusted OR 5.7; CI 1.5-22), and a higher early satiety score (p=0.008) (multivariate adjusted OR 6.7; CI: 1.9-23) in the subjects with high post-dexamethasone cortisol levels (low HPA suppression) compared with the subjects with intermediate post dexamethasone cortisol levels. Furthermore, individuals with low post dexamethasone cortisol levels (high HPA suppression) showed a significant, higher score for diarrhoea (median 2.0 versus 0; p =0.010) (multivariate adjusted OR 6.1; CI 1.8-20) and early satiety (p=0.076) (multivariate adjusted OR 3.2; CI 1.0 10) compared with those with intermediate cortisol levels. CONCLUSIONS: A trend toward a non-linear relationship between IBS-like symptoms and post-dexamethasone cortisol levels was observed in healthy individuals, with significantly more symptoms of diarrhoea and early satiety in individuals with high or low post dexamethasone cortisol levels in comparison with those with intermediate post dexamethasone cortisol levels. PMID- 17852842 TI - Polymorphism in the promoter region of the NFKB1 gene increases the risk of sporadic colorectal cancer in Swedish but not in Chinese populations. AB - OBJECTIVE: An insertion/deletion polymorphism (-94ins/delATTG) in the promoter region of the NFKB1 gene correlates to an increased risk of ulcerative colitis, a known risk factor for colorectal cancer, but this polymorphism has not been studied in colorectal cancer patients. The purpose of this study was to investigate whether this polymorphism is related to colorectal cancer risk and clinicopathological variables. MATERIAL AND METHODS: Case samples were taken from four groups of Swedish patients: 193 unselected patients, 90 patients with > or =3 affected 1st-degree relatives, 85 patients with 2 affected 1st-degree relatives, and 109 sporadic cancer patients, and one group of 193 unselected Chinese patients. Controls included 439 Swedish and 458 Chinese healthy individuals. Genotypes were determined by polymerase chain reaction (PCR) restriction fragment length polymorphism. RESULTS: The deletion increased the risk of colorectal cancer among Swedish unselected patients (OR =3.81, 95% CI: 2.17-6.69, p <0.0001 for heterozygote deletion, and OR=4.65, 95% CI: 2.43-8.89, p <0.0001 for homozygote deletion) and sporadic cancer patients (OR =7.73, 95% CI: 3.06-19.57, p <0.0001 for heterozygote deletion, and OR =6.58, 95% CI: 2.35 18.43, p <0.0001 for homozygote deletion) compared to homozygote insertion (wild type), but not among the other Swedish or Chinese patients (p >0.05). Similar evidence was seen in age-adjusted analyses (p <0.0001). The polymorphism did not correlate to clinicopathological variables (p >0.05). CONCLUSIONS: Deletion of the polymorphism was associated with increased susceptibility to sporadic colorectal cancers in the Swedish population, but not in the Swedish patients with a family history of colorectal cancer or in Chinese patients. PMID- 17852843 TI - Gastrointestinal investigation of iron deficiency anaemia detected by pre-blood donation screening. PMID- 17852844 TI - Influence of resistant starch alone or combined with wheat bran on gastric emptying and protein digestion in healthy volunteers. AB - OBJECTIVE: Resistant starch (RS) is not absorbed in the small intestine, but is partly fermented in the colon and may positively influence putative risk factors for colon cancer. The purpose of the study was to investigate the influence of RS type 3 (retrograded amylose) alone or combined with wheat bran on gastric emptying (GE) and protein assimilation. MATERIAL AND METHODS: GE and protein assimilation were investigated by means of breath-test technology in 20 healthy volunteers who were randomly divided into two groups, each subject performing two tests. In each test, the volunteers received a labelled test meal either as such or in combination with, respectively, 15 g RS3 or 15 g RS3 combined with 6 g wheat bran (WB). Breath samples were collected during the 6 h after administration of a test meal containing egg proteins, intrinsically labelled with (13)C-leucine, to measure protein digestion and sodium-(14)C-octanoate for measurement of GE. RESULTS: Intake of RS3 +WB did not influence GE time compared to baseline values, whereas intake of RS3 seemed to hasten GE: from 93 +/- 32 min to 55 +/- 15 min (p = 0.012). The overall protein assimilation parameters at baseline were not significantly different from those obtained after simultaneous intake of RS3 +WB, whereas RS3 significantly shortened the time of maximum excretion compared to baseline, but the extent of protein digestion after RS3 intake was not affected (12.54 +/- 3.60% versus 13.43 +/- 3.40%). CONCLUSIONS: The presence of RS3 alone or in combination with wheat bran demonstrates that there are no adverse effects on protein digestion and no influence on the nitrogen supply to the colon. PMID- 17852845 TI - Gastric emptying: a comparison of three methods. AB - OBJECTIVE: A better understanding of the clinical relevance of delayed gastric emptying (e.g. in diabetes) requires a simple, easily accessible and inexpensive method for measuring it. Two "new" methods for measuring gastric emptying of liquids (the paracetamol absorption test and the 13C-acetate breath test) are compared with the gold standard (gastric emptying scintigraphy (GES)). MATERIAL AND METHODS: The three techniques were used simultaneously in 10 healthy subjects. A gastric emptying time-retention curve was drawn for each technique and the results were compared at the 75%, 50% and 25% retention quartiles. RESULTS: Agreement was found between the paracetamol absorption test and GES (p=0.95; Hotelling's T 2 test). Using the Wagner-Nelson one compartment correction produced a retention curve for the 13C-acetate breath test statistically significantly below GES (p<0.01). CONCLUSION: In healthy subjects, the paracetamol absorption test produced results comparable to those of liquid GES, but not to the results of the 13C-acetate breath test. PMID- 17852846 TI - Renal function and cognitive impairment in patients with liver cirrhosis. AB - OBJECTIVE: Cognitive impairment is a common problem in patients with liver cirrhosis. Its pathogenesis is multifactorial and ammonia is considered to play a central role. Renal function has been shown to be important for ammonia metabolism in cirrhosis. Although renal dysfunction is common in cirrhotic patients, its effect on cognitive function is largely unexplored. MATERIAL AND METHODS: A total of 128 consecutive cirrhotic patients were prospectively evaluated for the presence of cognitive dysfunction according to the West-Haven criteria and by means of two psychometric tests. Serum creatinine, sodium and potassium as well as plasma ammonia concentrations were assessed. Glomerular filtration rate was also measured by (51)Cr- EDTA clearance in a subgroup of patients. RESULTS: Forty-one patients (32%) were found to have cognitive dysfunction (clinical evaluation and/or psychometric tests). Sixteen patients (13%) found with serum creatinine levels above reference values had cognitive dysfunction more frequently than patients with creatinine within the normal range (69% versus 31%; p = 0.001), but did not differ in aetiology or severity of cirrhosis (p >0.1). Patients with loop diuretics versus without did not differ in creatinine values (p >0.1). Multivariate analysis showed that cognitive dysfunction was related to hospital admission at inclusion in the study, international normalized ratio and serum creatinine (p <0.05 for all), but not to potassium or sodium levels. Plasma ammonia concentration was related to serum creatinine (r = 0.26, p = 0.004) and the glomerular filtration rate (r = -0.44, p = 0.023). CONCLUSIONS: Renal dysfunction seems to be related to cognitive impairment in patients with liver cirrhosis and might be implicated in the pathogenesis of hepatic encephalopathy. PMID- 17852847 TI - Influence of socio-economic deprivation on outcomes for patients diagnosed with oesophageal cancer. AB - OBJECTIVE: To determine the influence of deprivation on outcomes for patients with oesophageal cancer. MATERIAL AND METHODS: A total of 1196 consecutive patients with oesophageal carcinoma presenting to a regional multidisciplinary team between 1 January 1998 and 31 August 2005 were studied prospectively and deprivation scores calculated using the Indices of Multiple Deprivation (IMD) of the National Assembly for Wales. The patients were subdivided into quintiles for analysis. RESULTS: Inhabitants of the most deprived areas (quintile 5) were younger at presentation (median age 67 years versus 70 years, p = 0.01) and were more likely to have squamous cell carcinomas (SCCs) (p = 0.002) in comparison with patients from the least deprived areas (quintile 1). Stage of disease and morbidity did not correlate with deprivation quintile, but operative mortality was greater in quintile 1 versus 5 (1.9% versus 5.8%, p = 0.281). Overall 5-year survival for those patients undergoing oesophagectomy was unrelated to deprivation quintile (1 versus 5, 24% versus 33%, p = 0.8246), but was lower following definitive chemoradiotherapy (dCRT) for the least deprived quintiles (1, 2 & 3 versus 4 & 5, 35% versus 16%, p = 0.0272). CONCLUSIONS: Although deprivation was associated with younger age, SCC and a trend towards higher operative mortality, survival after diagnosis and oesophagectomy were unrelated to deprivation. PMID- 17852848 TI - No increased seroprevalence of anti-Yersinia antibodies in patients with type 1 (C282Y/C282Y) hemochromatosis. PMID- 17852849 TI - Prevalence and determinants of histological abnormalities of the gastric cardia in volunteers. AB - OBJECTIVE: The findings of studies examining the prevalence and major risk factors of histological abnormalities of the gastric cardia have been inconsistent. Selection bias was possible in these studies depending on whether patients were referred for ulcer or gastroesophageal reflux disease (GERD). There have been no studies on non-patient populations. The aim of this study was to mitigate the potential effects of selection bias. MATERIAL AND METHODS: In a study comprising health-care workers, we distributed symptom questionnaires and invitations to undergo upper endoscopy. A single endoscopist performed standard endoscopy and biopsy examinations (2 antral, 2 corporal, and 2 cardiac biopsies). Staining was done using triple stain. Two pathologists, who were blinded to the results of the questionnaires and endoscopy, interpreted and recorded the histological findings. RESULTS: A total of 226 participants underwent endoscopy. Gastric cardia, as defined by the presence of mucous glands, was identified in 191 subjects; mean age of the subjects was 45 years, 117 (61%) were women, and 49% were black. Active gastritis of the cardia was present in 58 (30.4%), chronic gastritis in 133 (69.6%), intestinal metaplasia (IM) in 29 (15.2%), and pancreatic metaplasia in 25 (13%). Direct (organisms) or indirect evidence (active anywhere or chronic gastritis in antrum or corpus) for Helicobacter pylori was present in all participants with active gastritis, 60% of subjects with chronic gastritis, and approximately half of those with IM of the cardia. Approximately 15% with chronic carditis had neither H. pylori nor GERD symptoms. There were also no significant differences in the prevalence of heartburn or acid regurgitation, or the use of histamine-2-receptor antagonists (H2RAs) or proton pump inhibitors (PPIs) between groups with and without active or chronic gastritis, IM, or pancreatic metaplasia, whereas active or chronic gastritis in the antrum or corpus and H. pylori infection were more frequent (1.5- to 2-fold) among those with histological abnormalities of the cardia. CONCLUSIONS: Active and chronic gastritis as well as intestinal metaplasia of the gastric cardia are relatively common in health-care worker volunteers. Although GERD symptoms are not significantly associated with these abnormalities, H. pylori infection is a strong risk factor. However, a considerable number of participants with chronic gastritis of the cardia have neither H. pylori nor GERD. PMID- 17852850 TI - Quantitative measurement of nitric oxide and hydrogen peroxide in Helicobacter pylori-infected Mongolian gerbils in vivo. AB - OBJECTIVE: Peroxynitrite formation, as reflected by nitrotyrosine expression, is low in Helicobacter pylori-infected Mongolian gerbils despite pronounced expression of radical-forming enzymes. The aim of the present study was to investigate in vivo whether H. pylori inhibits either one or both of the nitro- and oxyradical formation pathways. MATERIAL AND METHODS: Male Mongolian gerbils were infected with two different H. pylori strains, TN2GF4 and SS1. Six months after inoculation, direct measurement of NO and H2O2 was performed in vivo using electrochemical microsensors positioned in close proximity to the gastric mucosa. RESULTS: In the TN2GF4-infected animals the level of NO was significantly lower than that in controls. No significant difference in NO levels was detected between the SS1-infected group and the controls. H2O2 was significantly increased in the SS1 animals compared with that in controls after 6 months. The H2O2 level in the TN2GF4 group did not differ from that in controls. CONCLUSIONS: The results indicate that H. pylori infection is associated with strain-dependent functional inhibition of both the NO and oxyradical formation pathways in the gastric mucosa. PMID- 17852851 TI - Why do subjects with irritable bowel syndrome seek health care for their symptoms? AB - OBJECTIVE: Irritable bowel syndrome (IBS) is common in the population, but not all subjects seek professional health care for their symptoms. The aim of this study was to compare consulters in secondary/tertiary care with those in primary care and non-consulters by using questionnaires to investigate factors of importance for health-care seeking in IBS. MATERIAL AND METHODS: The study included 218 subjects with IBS: 70 non-consulters, 53 patients from primary care and 95 from secondary/tertiary care. The subjects completed questionnaires on gastrointestinal (GI) and psychological symptoms, coping resources, health related quality of life (HRQOL) and reasons for not seeking health care. RESULTS: Consulters (primary and secondary/tertiary care combined) had poorer HRQOL, more severe psychological symptoms, higher levels of GI-specific anxiety and poor coping resources compared with non-consulters, but the GI symptom severity was similar. Mental health and poor social, emotional and physical functioning were independently predictive of being a health-care seeker (r (2)=0.41). Independent predictors for being a consulter in secondary/tertiary care were a high degree of anxiety, low scores on physical functioning, physical role and food (IBSQOL) (r (2)=0.65). Several non-consulters reported mild symptoms and ability to control symptoms as reasons for not seeking health care. Having a close relative with similar symptoms reduced the need to seek health care. Thirty-six non-consulters had sought alternative care or advice from friends and/or relatives about their GI symptoms. CONCLUSIONS: GI symptom severity alone cannot explain the illness behavior in IBS. HRQOL and psychological symptoms are important for experience of GI symptoms and the health-care seeking pattern in IBS. PMID- 17852852 TI - Multiple inflammatory-, tissue remodelling- and fibrosis genes are differentially transcribed in the livers of Abcb4 (-/ - ) mice harbouring chronic cholangitis. AB - OBJECTIVE: Abcb4 (-/-) mice secrete phosphatidylcholine-free, cytotoxic bile and develop chronic cholangitis. The aim of this study was to identify differentially transcribed genes whose products contribute to the liver tissue pathology during this disease. MATERIAL AND METHODS: Hepatic gene transcription was measured in 3 , 6-, 9- and 20-week-old Abcb4 (-/-) mice (FVB.129P2-abcb4(tm1Bor)/J) using cDNA microarrays, with FVB/NJ Abcb4 (+/+) mice serving as controls. Focus was on inflammatory-, remodelling- and fibrosis genes. Marked differential transcription of inflammatory-, tissue remodelling- and fibrosis genes found by cDNA microarrays was verified by real-time polymerase chain reaction (PCR). Liver pathology was quantified by histopathology scoring. RESULTS: Transcription of clade A3 Serpin genes showed early, marked down-regulation. The chemokine genes Ccl2, Ccl20 and Cxcl10 were markedly up-regulated. Tissue remodelling- and fibrosis genes exhibiting markedly up-regulated transcription included: Ctgf, Elf3, Lgals3, Mmp12, Mmp15, Spp1, Loxl2, Pdgfa, Pdgfrb, Sparc, Tgfb1, Tgfb2, Tgfbi, Tgfbr2 and Col1a1, Col1a2, Col2a1, Col3a1, Col4a1 genes. Microarray-based recordings of differential gene transcription of the majority of these genes harmonized with the liver histopathology score. Thus, cDNA microarray-based analysis showed increasing differential transcription of several inflammatory-, tissue remodelling- and fibrosis genes during the first 9 weeks of disease and a tendency towards differential transcription to stabilize at an elevated level from 9 to 20 weeks of disease. CONCLUSIONS: Multiple genes regulating inflammation, tissue remodelling and fibrosis not previously linked to Abcb4 (-/ ) cholangitis are identified as being differentially transcribed in Abcb4 (-/-) livers, where they contribute to the pathogenesis of liver tissue pathology. PMID- 17852853 TI - Multidetector CT in patients with esophageal stent as a palliative treatment for stenosing esophageal cancer: a feasibility study. AB - OBJECTIVE: The self-expanding metallic stent (SEMS) is widely used in the palliative treatment of stenosing esophageal cancer. Multidetector computed tomography (MDCT) allows volumetric investigation including virtual endoscopy. The aim of this study was to determine the feasibility of MDCT follow-up of esophageal SEMS and to describe the imaging patterns encountered as well as correlating them with fibroscopic evaluation. MATERIAL AND METHODS: Thirteen consecutive patients (10 M, mean age 64 years) with esophageal SEMS as a palliative treatment underwent MDCT for recurrent dysphagia (n =7), chest pain and fever (n = 1) or follow-up without symptoms (n = 5). Patency and esophageal wall patterns were studied and compared with diagnosis by fibroscopy. RESULTS: No metallic artefact related to the SEMS was observed. At the SEMS level, MDCT revealed a tissular lump (n = 1), a thin recurrent layer of tissue (n = 1), extrinsic compression (n = 1), fluid stasis (n =7) and intussusception of the gastric wall into the SEMS (n =4). The esophageal wall was analyzed by MDCT (peripheral thickening around the stent (n = 8), tumor overgrowth under or above the SEMS level (n = 8)) and showed tracheal compression (n = 3). At the level of the SEMS, fibroscopy showed tumor recurrence (n = 2), a thin recurrent layer of tissue (n = 1), a distorted SEMS (n = 1) and a tumor overgrowth under or above the SEMS level (n = 6). In comparison with fibroscopy, MDCT satisfactorily diagnosed the SEMS patency in 92% of cases and the esophageal wall in 73%. CONCLUSIONS: Morphology, patency of the SEMS and analysis of the esophageal wall can be performed by MDCT with a good degree of accuracy as compared to fibroscopy. In such patients in palliative care, a non-invasive investigation is worth promoting as a first-line procedure. PMID- 17852855 TI - Hepatitis C virus and splenic marginal zone lymphoma with villous lymphocytes: away from conventional therapy. PMID- 17852854 TI - Coeliac disease and hearing loss: preliminary data on a new possible association. AB - OBJECTIVE: Coeliac disease (CD), an autoimmune gluten-dependent enteropathy, can be associated with several extra-intestinal manifestations, including neurological disorders. At present, no data are available on the presence of hearing loss disorder in coeliac patients. The aim of the present study was to investigate the prevalence of hearing loss in coeliac patients compared with that in healthy controls. MATERIAL AND METHODS: Twenty-four adult coeliac patients and 24 healthy subjects matched for gender, age, smoking and drinking habits were enrolled in the study. Among the coeliac patients, 6 were newly diagnosed and 18 patients were on a gluten-free diet for at least one year. RESULTS: A hearing loss was found in 10 (47.1%) coeliac patients and 2 (9.1%) healthy controls. All CD patients with hearing loss presented a sensorineural hearing loss. The prevalence of hearing loss was significantly higher in coeliac patients than in healthy controls (p = 0.01) but it was not significantly different between untreated (33.3%) and treated (44.4%) coeliac patients (p: NS). CONCLUSIONS: Despite the low number of subjects evaluated, the present study showed a higher prevalence of hearing loss in coeliac patients than in healthy controls, suggesting an association between CD and hearing loss. Immunological processes such as ear-specific and non-specific autoantibodies and vasculitis could be the basis of this association. Further longitudinal investigations on a larger sample size will be necessary to confirm the present data. PMID- 17852856 TI - Bile acids induce overexpression of homeobox gene CDX-2 and vascular endothelial growth factor (VEGF) in human Barrett's esophageal mucosa and adenocarcinoma cell line. AB - OBJECTIVE: Barrett's esophagus (BE) is an acquired precancerous condition that develops from mucosal injury incurred after chronic gastroesophageal acid and bile reflux. The mechanism of progression of carcinogenesis in BE is still not fully understood. Recently, the role of bile acids and the homeobox gene transcription factor CDX-2 has been suggested in the pathogenesis of BE. The aims of the present study were 1) to compare the mRNA and protein expression of CDX-2 in biopsies obtained from patients with BE and normal squamous epithelium and 2) to study the effect of two different bile salts, ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA), on the mRNA expression of CDX-2 and vascular endothelial growth factor (VEGF) in Barrett's the adenocarcinoma cell line (OE-33). MATERIAL AND METHODS: CDX-2 expression was measured in Barrett's mucosa and normal esophageal mucosa obtained from 15 patients with BE histologically diagnosed by immunohistochemistry, Western blot, and quantitative reverse transcriptase polymerase chain reaction (RT-PCR). In in vitro experiments, OE-33 cells were incubated with DCA (100 microM) and UDCA (100 microM) in neutral and shortly acidified media (pulse acidification). The expression of CDX-2 and VEGF was assessed by quantitative RT-PCR. RESULTS: Both mRNA and protein expression of CDX 2 were significantly up-regulated in Barrett's mucosa as compared to normal esophageal mucosa. In neutral medium, OE-33 cells showed an increase in CDX-2 expression after incubation with DCA or UDCA. After short acidification of the medium, expression of CDX-2 in OE-33 cells was significantly higher than that in cells incubated in neutral pH. The addition of DCA and UDCA did not cause any further alteration in CDX-2 expression. In neutral and acidified medium, VEGF mRNA expression was only significantly up-regulated by DCA, but not by UDCA. CONCLUSIONS: Bile acids, especially in acidic medium, increase expression of CDX 2. DCA appears to be a stronger stimulant of the expression of VEGF than UDCA in the Barrett's carcinoma cell line, indicating a stronger carcinogenic potential of this bile salt. PMID- 17852857 TI - A rare surgical case of metachronous double carcinoma of the biliary tract. AB - We report on a rare case of metachronous double carcinoma of the biliary tract, occurring in a 65-year-old male. The patient was admitted to the hospital with jaundice in March 2004. Ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) scans of the abdomen showed a minimally dilated intrahepatic biliary tree with normal-appearing choledocus. Obstruction of the common hepatic duct was revealed by endoscopic retrograde cholangiopancreatography (ERCP). The patient underwent a resection of the middle third of the extrahepatic duct and cholecystectomy (cholangiocarcinoma, pT1N0M0), with the surgical margins of resection showing as negative. After 2 years, during follow-up, the findings of a positron emission tomography (PET)-CT scan suggested a possible cholangiocarcinoma of the distal part of the biliary tract; CT and MRI scanning of the abdomen showed mild dilatation of the distal common hepatic duct; an ERCP showed mild dilatation of the retropancreatic remnant of the biliary tree with endoluminal defects. Eventually the patient underwent pancreaticoduodenectomy. The histopathological diagnosis of the resected specimen confirmed a cholangiocarcinoma; 10 lymph nodes were negative (pT1N0M0). At 6 months post-op after the second operation the patient is progressing well with no signs of recurrence. Patients with cholangiocarcinoma - in whom survival is prolonged with surgical resection - should undergo careful follow-up for both recurrence and second primary cancer. PET scanning seems to play the most important diagnostic role. PMID- 17852858 TI - Autologous blood as a submucosal fluid cushion for endoscopic mucosal therapies: results of an ex vivo study. AB - OBJECTIVE: Submucosal injection of fluid is used to elevate lesions in order to prevent perforation, which is the most calamitous complication during endoscopic resection therapies. There are several injection options when performing mucosal elevation (normal saline (NS), sodium hyaluronate (SH), etc.). Submucosal injection of fresh, autologous blood offers some advantages because of its specific properties: corpuscular components ensure prolonged elevation and procoagulatory constituents prevent post-interventional bleeding. The purpose of this study was to compare the ex vivo performance of autologous blood as a submucosal fluid cushion (SFC) with that of NS, SH and DW (dextrose water). MATERIAL AND METHODS: The proximal third of a resected porcine stomach was cut into squares. One millilitre NS, DW, SH and fresh porcine blood was injected into the submucosa. The height and duration of the submucosal injections were objectively measured during 1 h. Mucosal elevations were resected using an electro snare. RESULTS: The initial height and width of the mucosal elevations were comparable for SH and blood, and significantly higher compared with NS and DW. Mucosal elevation after injecting autologous blood persisted significantly longer compared with NS (p <0.05), but did not differ from hyaluronate. Histopathological examination of the resected specimen confirmed the appropriate submucosal injection of these substances. CONCLUSIONS: Submucosal injection of autologous blood with a standard endoscopic injection needle is possible and generates adequate mucosal elevation for the resection of high-quality specimens. This procedure could offer a "gratis" option for SFC as opposed to the expensive SH. Further clinical studies are needed to substantiate its use. PMID- 17852859 TI - Clinical effectiveness of probiotics therapy (BIO-THREE) in patients with ulcerative colitis refractory to conventional therapy. AB - OBJECTIVE: Intestinal microflora has been implicated in the etiology of ulcerative colitis (UC). Over the past few years, the use of probiotics in UC has gained attention. The aim of this study was to evaluate the efficacy of probiotics therapy for mild to moderate distal UC refractory to conventional therapies. MATERIAL AND METHODS: Twenty patients with mild to moderate distal UC took 9 BIO-THREE tablets per day for 4 weeks. Clinical symptoms and endoscopic findings were evaluated as ulcerative colitis disease activity index (UCDAI) scores before and after administration of BIO-THREE. Fecal samples were collected from all patients before and after probiotics administration, and fecal microflora was analyzed by the terminal restriction fragment length polymorphism (T-RFLP) method. RESULTS: Remission (UCDAI score < or =2) was observed in 45% (9/20) of the patients; response (decrease in UCDAI > or = 3, but final score > or = 3) in 10% (2/20); no response in 40% (8/20); and worsening (UCDAI > 3) in 5% (1/20). T-RFLP analysis indicated that the principal alteration in microflora was an increase in bifidobacteria. CONCLUSIONS: This study showed that administration of BIO-THREE improved the clinical symptoms and endoscopic findings in patients with UC, indicating that administration of BIO-THREE is safe and efficacious for the treatment of UC. PMID- 17852860 TI - Relationship between fecal lactoferrin and inflammatory bowel disease. AB - OBJECTIVE: Lactoferrin as a glucoprotein that can reflect the activity of neutrophil leukocytes is a specific and sensitive indicator in the evaluation of intestinal inflammation. The aim of this study was to evaluate the relationship between fecal lactoferrin and intestinal inflammation by quantitative analysis and the effect of fecal lactoferrin in measuring the activity of inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD). MATERIAL AND METHODS: A total of 177 fresh stool samples were collected from 42 active UC, 17 inactive UC, 13 active CD, 5 inactive CD, 41 infectious bowel disease, 25 irritable bowel syndrome (IBS) and 34 healthy volunteers. IBD-SCAN was used quantitatively to measure the level of fecal lactoferrin. A modified Harvey-Bradshaw Active Index was used to evaluate the activity of IBD. RESULTS: Fecal lactoferrin was 3.15+/-1.60 microg/g in healthy volunteers, 2.54+/-1.49 microg/g in IBS, 83.3+/-29.9 microg/g in infectious bowel disease, 1126.29+/ 431.21 microg/g in active UC, 1035.25+/-456.59 microg/g in active CD, 96.58+/ 82.46 microg/g in inactive UC and 133.52+/-88.89 microg/g in inactive CD. Fecal lactoferrin was significantly higher in active IBD than in inactive IBD, IBS and infectious bowel disease. The sensitivity and specificity of fecal lactoferrin were 92% and 88%, respectively, for UC, and 92% and 80%, respectively, for CD. CONCLUSIONS: Fecal lactoferrin is a sensitive and specific marker in measuring the activity of IBD. It provides us with a valid method in discriminating between inflammatory and non-inflammatory bowel disease. In addition, an elevated fecal lactoferrin level can lead us to exclude IBS in clinical practice. PMID- 17852861 TI - Corticosteroid-binding globulin: a possible early predictor of infection in acute necrotizing pancreatitis. AB - OBJECTIVE: Infected pancreatic necrosis is the main cause of death in patients with acute pancreatitis, and therefore its early prediction is of utmost importance. Endogenous cortisol metabolism plays a basic role both in the course of acute pancreatitis and in the process of infection. The purpose of this study was to analyze corticosteroid-binding globulin (CBG), total cortisol, calculated free cortisol and adrenocorticotropic hormone as potential early predictors in order to differentiate between infected pancreatic necrosis and sterile pancreatic necrosis in patients with acute pancreatitis. MATERIAL AND METHODS: Serum levels of CBG, total cortisol, calculated free cortisol, and plasma levels of adrenocorticotropic hormone were determined in 109 consecutive patients with acute pancreatitis. C-reactive protein was measured as the control parameter. Thirty-five patients developed necrotizing pancreatitis and 10 developed infection of the necrosis. Blood was monitored for 6 days after the onset of pain; 30 healthy individuals served as controls. RESULTS: Of all parameters only CBG showed a significant difference (p = 0.0318) in its peak levels measured in the first 48 h in patients with sterile (26.5 microg/ml, range 21.3-34.7) and infected (16.0 microg/ml, range 15.2-25.0) necrosis at a cut-off level of 16.8 microg/ml. That difference was further preserved for the first 6 days after onset of pain. CONCLUSIONS: In our group of patients, a decreased CBG level below 16.8 g/ml within the initial 48 h of acute pancreatitis was an early predictor of later infected pancreatic necrosis, with a positive predictive value of 100% and a negative predictive value of 87.5%. PMID- 17852862 TI - MMP-1 (collagenase-1) expression in primary colorectal cancer and its metastases. AB - OBJECTIVE: The role of MMP-1 (collagenase-1) in the development of a metastatic phenotype in colorectal cancer (CRC) has not been fully studied. The aim of this study was to investigate the mechanisms involved in the dissemination of CRC by examining the expression of MMP-1 in the primary tumours and their metastases, with special reference to standard clinicopathological features and disease outcome. MATERIAL AND METHODS: Surgical specimens from the primary tumours (P) and their metastatic (M) lesions were available from 30 patients with Stage II, III and IV CRC, and were subjected to immunohistochemical (IHC) staining for MMP 1. Both cytoplasmic expression in cancer cells (CC) and stromal (ST) expression were related to pertinent clinical and follow-up data. RESULTS: In a pairwise comparison of P-M pairs, CC expression (but not ST expression) in P and M was significantly different (Wilcoxon rank test, p=0.037). Strong CC expression in P was significantly related to the presence of lymph node involvement at diagnosis (p=0.008). CC expression in M was intense only in metachronous metastases (Stage II/III disease) but never in synchronous metastases (Stage IV) (p=0.034). There was a significant down-regulation of CC (p=0.004) in liver metastasis (n=9) in comparison with all other metastatic sites (n=21). ST expression in P (but not in M) showed a linear decrease in parallel with increasing stage (p=0.028 for linear trend). MMP-1 expression was not significantly associated with any other clinicopathological variables, including age, gender, carcinoembryonic antigen (CEA) or patients' disease-free or overall survival. CONCLUSIONS: These data suggest that MMP-1 may play an important role in tumour invasion and metastasis of CRC. PMID- 17852863 TI - Nitrogenous chemicals generated from acidification of saliva influence transient lower oesophageal sphincter relaxations. AB - OBJECTIVE: Saliva contains high concentrations of nitrite derived from the enterosalivary recirculation of dietary nitrate and its reduction by buccal bacteria. Acidic gastric juice converts the swallowed nitrite to varying proportions ofnitrous acid and nitric oxide (NO) depending upon ascorbic acid availability. Neuronally generated NO is the key in the pathway of transient lower oesophageal sphincter relaxations in vivo. Furthermore, in vitro NO and nitrous acid relax the smooth muscle of the stomach, lower oesophageal sphincter (LOS) and oesophageal body. The objective of this article was to determine whether luminal administration of NO or nitrous acid affects the generation of transient LOS relaxations following a meal. MATERIAL AND METHODS: Fifteen healthy subjects were studied on three separate days. A manometry catheter was used to record oesophageal, LOS and gastric pressures, and two oesophageal pH probes were used to record reflux. One of three solutions was infused each day into the cardia after a standardized meal: 1) control solution ofhydrochloric acid pH 1.0, 2) nitrous acid and 3) nitrous acid plus ascorbic acid to generate NO. The solutions were randomized and double-blinded. RESULTS: The frequency of transient LOS relaxations was increased by the NO-generating solution at 5.2/h compared with both the control (3.5, p <0.01) and nitrous acid solution (3.1, p <0.0001). The NO-generating solution also increased oesophageal acid exposure to 62.2%, compared with both the control (37.5%, p <0.03) and nitrous acid solution (36.6%, p <0.002). CONCLUSIONS: Luminal NO at the gastro-oesophageal junction increases the generation of transient LOS relaxations following a meal. Chemicals generated by the acidification of salivary nitrite may contribute to gastro-oesophageal motility disorders. PMID- 17852864 TI - Fecal pyruvate kinase: a potential new marker for intestinal inflammation in children with inflammatory bowel disease. AB - OBJECTIVE: Inflammatory bowel disease (IBD) in children creates diagnostic and clinical challenges. Clinical data, endoscopic appearance and the histopathological assessment of biopsies are essential for diagnosis. However, new methods are required for non-invasive follow-up. Recently, we demonstrated that the dimeric isoform of pyruvate kinase (PK) detected in stool might serve as a potential non-invasive screening tool in inflamed pouch mucosa. The aim of this study was to investigate whether this test could be used to detect intestinal inflammation in pediatric IBD patients. MATERIAL AND METHODS: Fecal PK immunoreactivity was assessed in 75 patients with proven ulcerative colitis (UC) and 32 with Crohn's disease (CD). Pediatric Crohn Disease Activity Index (PCDAI) and Truelove-Witts scores were determined in CD and UC patients, respectively. Thirty-five healthy subjects (HS) served as a control group. RESULTS: Increased PK levels were documented in 94.1% and 100% active CD patients with a cut-off level of 5 U/g and a cut-off level of 4 U/g, respectively, and in 94.3% of active UC patients regardless of cut-off level. Enzyme immunoreactivity was significantly higher in all IBD patients than in HS. Abnormal PK results were documented in 71.7% of all IBD patients (65.3% and 84.4 for UC and CD patients, respectively). Enzyme levels in UC remission were significantly lower than in the active phase. Enzyme immunoreactivity significantly correlated to both scoring systems. CONCLUSIONS: The measurement of stool PK could be a potentially useful marker of IBD activity in children. However, its clinical value demands further studies for comparison with other tests. PMID- 17852865 TI - Double-balloon enteroscopy versus magnetic resonance enteroclysis in diagnosing suspected small-bowel Crohn's disease: results of a pilot study. AB - OBJECTIVE: Small-bowel manifestations are common complications in Crohn's disease (CD) but can often be underestimated because of diagnostic limitations. Double balloon enteroscopy (DBE) is a new endoscopic method that provides complete visualization and biopsy sampling of the small bowel with potential implications for diagnosis and therapy. The purpose of this study was to compare the diagnostic yield of DBE and magnetic resonance enteroclysis (MRE) in patients suspected of having small-bowel CD. MATERIAL AND METHODS: Ten patients were consecutively selected and included in the study. In all patients a DBE of the small bowel was performed, the endoscopist being unaware of the radiological findings. Evaluation criteria included the presence of pathology, localization, degree, and extension of affection according to predefined morphologic criteria. Samples for histopathological investigation were taken in all patients with abnormal mucosa. RESULTS: In 50% of the patients (5 out of 10) with suspected small-bowel CD, DBE revealed pathological results. Here, in four patients, CD was verified histologically. A new diagnosis had to be established in one patient diagnosed for malignant lymphoma. The medical management had to change in five patients. In two patients, both DBE and MRE showed no pathological results; in three patients, superficial lesions were identified by MRE, whereas DBE was normal. CONCLUSIONS: In selected patients with suspected small-bowel lesions, DBE is a promising tool in the diagnostic work-up and provides the advantage of biopsy sampling. In contrast, non-invasive MRE delivers excellent information about extraluminal pathology associated with CD. Both MRE and DBE have the potential to become diagnostic standards that complement each other in patients with suspected complex small-bowel CD. PMID- 17852866 TI - Tissue levels of tumor necrosis factor-alpha correlates with grade of inflammation in untreated ulcerative colitis. AB - OBJECTIVE: The immune characterization of ulcerative colitis (UC) has been unclear and controversial. One possible explanation for the discrepancies between earlier cytokine studies in UC may be the fact that the patients included were on immunosuppressive therapy. Thus, the aim of this study was to determine the tumor necrosis factor-alpha (TNF-alpha) level and T(H)1/T(H)2 cytokine expression (mRNA) profile in patients with untreated UC. MATERIAL AND METHODS: Forty-four untreated UC patients, 10 untreated Crohn's disease (CD) patients and 28 healthy controls were included in the study. Colon biopsies were processed for quantitative measurements of TNF-alpha, interleukin (IL)-10, IL-18, IL-4 and interferon-gamma (IFN-gamma) mRNA using real-time polymerase chain reaction (PCR). TNF-alpha expression in T-cell lymphocytes (CD3) and macrophages (CD68) were further characterized by immunohistochemistry (IHC). RESULTS: Compared with the level in normal controls, the TNF-alpha mRNA level in UC patients was clearly increased, especially in patients with moderate to severe disease. The levels of TNF-alpha mRNA increased in proportion to the UC Disease Activity Index (UCDAI) score in UC patients. Differences were also observed between UC and controls for IFN-gamma IL-18, IL-4 and IL-10. Only minor quantitative differences in cytokines were observed between UC and CD, and they were more or less similar when comparing moderate to severe UC and CD. CD3+ lymphocytes and macrophages in lamina propria from CD and UC lesions showed increased intracellular staining of TNF-alpha. CONCLUSIONS: TNF-alpha is highly expressed in UC and correlates to the grade of inflammation. The sources of TNF-alpha were observed both in CD3+ lymphocytes and in macrophages. Cytokine expression (mRNA) profiles seem to be similar in patients with moderate to severe UC and CD. PMID- 17852867 TI - Association between CDH1 haplotypes and gastric cancer risk in a Japanese population. AB - OBJECTIVE: A c. -285C >A single nucleotide polymorphism (SNP) in the promoter region of the E-cadherin (CDH1) gene, which is a tumor suppressor in gastric cancer (GC), has been shown to decrease gene transcription, but GC case-control studies of this SNP have yielded controversial results. A haplotype study in an Italian population showed that haplotypes based on three SNPs, including the c. 285C >A, are associated with susceptibility to GC. Hence, the purpose of the present study was to carry out a more comprehensive genetic analysis of CDH1 using haplotype-tagging SNPs (htSNPs) in a Japanese case-control study to identify the CDH1 haplotype associated with susceptibility to GC in a Japanese population. MATERIAL AND METHODS: First, 11 SNPs in the CDH1 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 30 healthy individuals. Haplotype frequencies were estimated with the expectation-maximization algorithm, and 7 common haplotypes of the CDH1 gene whose frequency was at least 3.3% were identified. Next, 5 htSNPs (c. -285C >A, c.48+6T >C, c.164 -3159T >C, c.2076C >T, and c.2296 -616G >C) were genotyped in a hospital-based case-control study of 148 GC patients and 292 age- and gender matched healthy controls, and haplotype frequencies based on the 5 htSNPs were estimated. RESULTS: Although none of the 5 htSNPs was related to an overall risk of GC, frequencies of the ATCTG and CTTTG haplotypes were significantly higher and lower, respectively, in the GC cases than in the controls (p<0.05). CONCLUSIONS: These results suggest that the ATCTG and CTTTG CDH1 haplotypes may be associated with an increased risk and decreased risk, respectively, of GC in the Japanese population. PMID- 17852868 TI - Right-side shift of metachronous colorectal adenomas after polypectomy. AB - OBJECTIVE: In our previous study, we showed that the development of adenomas in the right-side colon increased with aging in subjects with no colorectal neoplasms. The aim of the present study was to investigate the location of metachronous colorectal adenomas after endoscopic polypectomy. MATERIAL AND METHODS: The records of a colonoscopic follow-up study on 2900 subjects after polypectomy were analyzed. The location was classified as the right-side colon and left-side colon at the splenic flexure. Subjects were classified into three groups according to distribution of adenomas at the initial two colonoscopies: those with adenomas located only in the left side (LL), adenomas in both the left side and right side (LR), and adenomas only in the right side (RR). Distribution of initial and metachronous adenomas was evaluated according to age. RESULTS: The annual incidence rates of colorectal adenomas in the left-side colon were estimated to be 8.56%, 11.2%, and 5.71% in the LL, LR, and RR groups, respectively. The rates in the right side were 5.91%, 15.5%, and 9.38%, respectively. The incidence rates in the left side in the age groups <40, 40-49, 50-59, and > or =60 years were 6.93%, 8.08%, 8.33%, and 8.48%/year, respectively. Those in the right side were 4.91%, 7.27%, 9.86%, and 12.41%/year, respectively. CONCLUSIONS: Although there may be individual predilection for right-side or left side location of colorectal adenomas, aging tends to increase the number of adenomas in the right-side colon, while only modestly affecting those in the left side colon. PMID- 17852869 TI - Serum and mucosal S100 proteins, calprotectin (S100A8/S100A9) and S100A12, are elevated at diagnosis in children with inflammatory bowel disease. AB - OBJECTIVE: Various markers characterize the complex inflammatory processes seen in chronic inflammatory bowel disease (IBD) including calprotectin, a complex of two S100 proteins, which has been evaluated and validated as a faecal marker of inflammation. However, the systemic and mucosal expression patterns of calprotectin and related S100 proteins are not well characterized in this disease. The objective of this study was to assess serum and mucosal levels of calprotectin, S100A12 and soluble receptor for advanced glycation end products (sRAGE), a putative S100 ligand, in a paediatric population with IBD. MATERIAL AND METHODS: Children were enrolled at diagnosis of IBD, along with groups of children without IBD. Standard inflammatory markers and disease activity scores were collated. Calprotectin, S100A12 and sRAGE levels in serum and biopsy culture supernatants were measured by ELISA and tissue distribution of S100 proteins was investigated by immunohistochemistry. RESULTS: Serum and mucosal calprotectin and S100A12 levels were increased in children with IBD as compared with non-IBD controls. Serum calprotectin levels correlated with S100A12 levels and with disease activity scores in children with IBD. sRAGE levels were not increased in IBD. S100A8, S100A9 and S100A12 were abundantly expressed throughout the lamina propria and epithelium in inflamed mucosa. In contrast, these proteins were present in the lamina propria, but not the epithelium, in non-inflamed mucosa. CONCLUSIONS: Serum calprotectin and S100A12 are increased in children with IBD and indicate disease activity. Elevated levels of these proteins are present in the colonic mucosa and may contribute to the pathogenesis of IBD. Furthermore, an imbalance between sRAGE and S100A12 may contribute to inflammatory changes present in IBD. PMID- 17852870 TI - Systematic expression profiling of the gastric H+/K+ ATPase in human tissue. AB - OBJECTIVE: The potassium-competitive acid blockers (P-CABs), comprise a new, innovative group of competitive and reversible inhibitors of the gastric H+/K+ ATPase. Our aim was to identify sites of expression of the H+/K+ ATPase that are potential targets of these compounds by examining the expression profile of the gastric H+/K+ ATPase in the human body from a broad range of tissues. MATERIAL AND METHODS: Expression profiling was done by quantitative mRNA analysis (TaqMan PCR). Tissues that were mRNA-positive for the alpha subunit were investigated further by Western blot and immunohistochemistry (IHC) for the presence of gastric H+/K+ ATPase protein. RESULTS: In addition to the very high expression levels in the stomach, the adrenal gland, cerebellum and pancreas gave unexpectedly positive mRNA signals for the alpha subunit of gastric H +/K+ ATPase. However, they were negative for mRNA of the beta subunit, and Western blot and IHC were negative for alpha and beta subunit protein. Another group of tissues with low alpha subunit mRNA expression including the frontal cortex, cortex grey matter, testis, thymus and larynx submucosa were also found negative for both alpha and beta subunit protein. In contrast to mouse kidney, no gastric H+/K+ ATPase could be detected in human kidney. CONCLUSIONS: We therefore conclude that the only organ in humans expressing significant levels of the P-CAB target gastric H+/K+ ATPase is the stomach. PMID- 17852871 TI - A multiprofessional education programme for patients with inflammatory bowel disease: a randomized controlled trial. AB - OBJECTIVE: Health-related quality of life is impaired in patients with inflammatory bowel disease and improved disease-related information can improve this situation. The aims of this study were to create an education programme that could be readily applicable at the clinic and would be suitable for newly diagnosed patients with inflammatory bowel disease, and to investigate whether the programme could improve their health-related quality of life. MATERIAL AND METHODS: Ninety-three patients with inflammatory bowel disease in remission were included and randomized to an intervention group or a control group. The intervention group attended a multiprofessional education programme while the control group received regular information. Four questionnaires were used for measuring health-related quality of life. Both groups completed the questionnaires at baseline and after 6 months. The intervention group also completed the questionnaires after 1 month. RESULTS: No significant differences were found when comparing the two groups at 6 months. However, the multi professional education programme was highly appreciated by the patients. CONCLUSIONS: In the present study no improvement could be seen in health-related quality of life in patients with inflammatory bowel disease after participating in an education programme in comparison with the control group. This might be due to the fact that the questionnaires were not sensitive enough or that some patients were not in clinical remission. The patients' enthusiasm for the multiprofessional education programme has led to its being part of the regular care at the clinic. PMID- 17852872 TI - Barrett's oesophagus: intestinal metaplasia is not essential for cancer risk. AB - OBJECTIVE: Barrett's oesophagus is the main identifiable risk factor for oesophageal adenocarcinoma. It has been suggested that only patients with intestinal metaplasia are at risk of cancer, but the British Society of Gastroenterology (BSG) guidelines suggest that glandular mucosa is all that is needed. The aim of this study was to quantify the risk of adenocarcinoma in columnar-lined lower oesophagus, with or without specialized intestinal metaplasia. MATERIAL AND METHODS: All patients who had endoscopic biopsies of the lower oesophagus between 1980 and 1994 in a single-centre teaching hospital were included in the study. All histological specimens were re-examined and reported according to whether they contained columnar epithelial-lined lower oesophagus, glandular mucosa, with or without intestinal metaplasia. The primary outcome measure was the development of adenocarcinoma. RESULTS: In total, 712 patients were identified. Of these, 379 (55.1%) were found to have specialized intestinal metaplasia (SIM), and the remaining 309 (44.9%, p = NS) were reported as having glandular mucosa (GM). The median follow-up for patients was 12 years (range 8-20 years). Twenty-eight patients went on to develop adenocarcinoma (4.1%) during the follow-up period - 17 in the SIM group (4.5%) and 11 in the GM group (3.6%, p =NS). The oesophageal malignancy rate was 0.34% per year (SIM 0.37%, GM 0.30%; p =NS). CONCLUSIONS: Patients who have glandular mucosa on biopsy without intestinal metaplasia have a similar cancer risk to those with specialized intestinal metaplasia. PMID- 17852874 TI - Dihydroxy bile acids increase mucosal permeability and bacterial uptake in human colon biopsies. AB - OBJECTIVE: Bile acids in mM concentrations are known to increase chloride secretion and alter mucosal permeability in animal colon. Increased mucosal permeability is believed to play an important role in the development of intestinal inflammation. The aim of this study was to investigate the influence of microM concentrations of dihydroxy bile acids on permeability and bacterial uptake in the normal human colon. MATERIAL AND METHODS: Endoscopic biopsies from the sigmoid colon of 18 subjects with normal colonic histology were mounted in modified Ussing chambers. Chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) were added to the mucosal compartment. Short-circuit current (Isc) and transepithelial resistance (TER) were studied for 120 min. Cr-EDTA and horseradish peroxidase (HRP) were used to assess paracellular and transcellular permeability, respectively. The transmucosal passage of chemically killed Escherichia coli was quantified and investigated using confocal microscopy. RESULTS: A significant decrease in TER was seen after 60 min of exposure to 1000 micromol/l CDCA and DCA. The combination of E. coli and 100 micromol/l CDCA gave a decrease in TER compared to controls (p = 0.06). DCA showed a dose-related increase in Cr-EDTA permeability, which was most pronounced at 1000 micromol/l (p = 0.02). Increased E. coli uptake was induced by 500 micromol/l (p = 0.01) and 1000 micromol/l CDCA (p = 0.04). Bacterial uptake was increased at 100 micromol/l by exposure to DCA (p = 0.03). Confocal microscopy revealed the presence of E. coli bacteria in the lamina propria after 15 min of exposure to 1000 micromol/l CDCA and DCA. CONCLUSIONS: Our study suggests that dihydroxy bile acids in microM concentrations alter barrier function in normal human colon biopsies, causing increased antigen and bacterial uptake; thereby bile acids may contribute to the development of intestinal inflammation. PMID- 17852875 TI - Factors associated with non-attendance at outpatient endoscopy. AB - OBJECTIVE: Non-attendance at endoscopy procedures leads to wasted resources and increased costs. The purpose of this study was to investigate the factors associated with non-attendance. MATERIAL AND METHODS: All patients who attended the outpatient clinic for gastroscopy or colonoscopy examinations were included in the study. Patients who missed their appointment were identified and their data were collected prospectively. Patients who kept their appointment in the same period of time served as controls. RESULTS: Between August 2002 and February 2003, 1051 gastroscopies and 756 colonoscopies were scheduled. A total of 265 patients (14.7%) missed their appointment. No significant differences were found between attendees and non-attendees for mean age, gender, type of examination and day of the week on which the examination was scheduled. The time on the waiting list was longer in patients who did not keep their appointment than in those who did. Fewer appointments were missed in patients with a preferent referral, and among patients referred by their general practitioner a higher percentage failed to keep their appointment compared with those referred by a specialist. In the multivariate analysis, length of time on the waiting list and the source of referral were the only two independent predictive factors for non-attendance. CONCLUSIONS: A longer time on the waiting list and referral by a general practitioner are factors associated with patients failing to keep their endoscopy appointment. PMID- 17852876 TI - Rectal nitric oxide and fecal calprotectin in inflammatory bowel disease. AB - OBJECTIVE: The assessment of intestinal inflammation in patients with inflammatory bowel disease (IBD) remains a difficult challenge. Both rectal nitric oxide (NO) and fecal calprotectin can be measured using non-invasive methods and are emerging as promising inflammatory markers in IBD. In this study the aim was to compare calprotectin and NO levels in IBD patients. MATERIAL AND METHODS: Rectal NO was measured tonometrically in 23 healthy volunteers and 32 patients with IBD. In addition, we collected stool samples from all subjects for measurement of fecal calprotectin and nitrate/nitrite (NO metabolites). RESULTS: Patients with IBD had greatly increased NO and calprotectin levels compared to healthy volunteers (p <0.001). In addition, the nitrate levels were slightly increased in IBD patients. A weak correlation was found between rectal NO levels, disease activity and number of loose stools in IBD patients (Spearman's rho 0.37 and 0.51, respectively; p <0.05). Fecal calprotectin correlated only with age (Spearman's rho 0.51; p <0.01). However, no correlation was found between NO and calprotectin. CONCLUSIONS: Both rectal NO and fecal calprotectin are greatly increased during bowel inflammation, but they may reflect different parts of the inflammatory process. Future studies will elucidate the clinical usefulness of these two markers. PMID- 17852877 TI - Elevated B cell-activating factor of the tumour necrosis factor family in coeliac disease. AB - OBJECTIVE: The B cell-activating factor of the tumour necrosis factor (TNF) family (BAFF) was recently described as a critical survival factor for B cells, and its expression is increased in several autoimmune diseases. Abnormal production of BAFF disturbs immune tolerance allowing the survival of autoreactive B cells and participates in the progression of B-cell lymphomas. Coeliac disease (CD) is a common autoimmune disorder induced by gluten intake in genetically predisposed individuals, associated with autoantibody production and with an increased risk of lymphoma at follow-up. The purpose of this study was to investigate the possible implications of BAFF in CD. MATERIAL AND METHODS: Seventy-three patients with small-bowel biopsies and laboratory-proven diagnosis of CD were included in the study. All serum samples were analysed before the start of a gluten-free diet (GFD). In 12 cases, one or more samples were analysed during follow-up of the GFD. Seventy-seven blood donors were taken as controls. Serum BAFF levels and anti-transglutaminase (a-tTG) antibodies were assessed by ELISA and endomysial antibodies by indirect immunofluorescence. RESULTS: Serum BAFF levels appeared to be significantly more elevated in CD patients than in controls (p<0.0001) and, compared with other autoimmune diseases where BAFF is increased, a much larger percentage (80.8%) of CD patients presented BAFF levels above the normal range. In addition, serum BAFF levels were found to correlate with a-tTG antibody levels (p =0.0007) and there was a significant reduction of BAFF after introduction of a GFD. CONCLUSIONS: BAFF may represent a possible pathogenic factor in CD. Its implications for the diagnosis, prognosis and treatment of CD should also be assessed. PMID- 17852878 TI - Resurrection of gliadin antibodies in coeliac disease. Deamidated gliadin peptide antibody test provides additional diagnostic benefit. AB - OBJECTIVE: Circulating antibodies against naive, whole gliadin have been replaced by more accurate endomysial and tissue transglutaminase antibody tests in the diagnosis of coeliac disease. The purpose of this study was to compare these serological tests with a new test recognizing antibodies against deamidated and defined gliadin peptides. MATERIAL AND METHODS: The study population comprised selected coeliac disease patients in a tertiary clinic: newly detected patients before and after a gluten-free diet, patients with persistent small-bowel mucosal villous atrophy despite a strict gluten-free diet and non-coeliac controls reporting abdominal symptoms after ingestion of cereals. Comparisons were made between serum IgA-class gliadin peptide, endomysial, tissue transglutaminase and conventional gliadin antibodies. RESULTS: The deamidated gliadin peptide antibody test showed a sensitivity of 91% and a specificity of 98% in coeliac disease. The tissue transglutaminase antibody test performed equally well. The specificity of endomysial antibody was just as high, but its sensitivity was lower, 80%. The conventional gliadin antibody test showed poor sensitivity and specificity. Combination of the deamidated gliadin peptide and tissue transglutaminase tests offered the best sensitivity without loss of specificity in the diagnosis of coeliac disease. All antibody levels declined in line with mucosal recovery. The deamidated gliadin peptide antibody test showed six of the nine cases with small bowel mucosal damage persisting on a gluten-free diet, whereas tissue transglutaminase detected only two cases and endomysial antibody none. CONCLUSIONS: The new gliadin peptide antibody test proved highly accurate in the diagnostic work-up and follow-up of coeliac disease and can be endorsed in combination with the tissue transglutaminase test. PMID- 17852879 TI - Laparoscopic observations of the liver in hereditary hemorrhagic telangiectasia. PMID- 17852880 TI - Gut microflora associated characteristics in first-degree relatives of children with celiac disease. AB - OBJECTIVE: In celiac disease (CD), enteropathy of the small bowel results from a T-cell-mediated reaction to gluten in the diet. In addition to gluten, other environmental and genetic factors participate in the disease pathogenesis. We have recently reported the finding of a significantly different short-chain fatty acid (SCFA) profile in fecal samples from children with CD compared to healthy controls reflecting an aberrant gut microflora. The aim of the present study was to make a functional evaluation of the gut microflora status in non-celiac 1st degree relatives of children with CD. MATERIAL AND METHODS: Fecal samples from 76 symptom-free, non-celiac, 1st degree CD relatives and from 91 aged-matched healthy controls were analyzed for fecal tryptic activity (FTA) and a number of SCFAs. RESULTS: There was a significantly lower level of acetic acid and total SCFAs as well as a significantly increased level of i-butyric acid and FTA in relatives compared to healthy controls. CONCLUSIONS: The FTA and the SCFA profiles in fecal samples from 1st degree relatives of children with CD are different from those of healthy individuals. The implication of this observation provides insight into the pathogenesis of CD and opens up the possibility of future new diagnostic, therapeutic and prophylactic strategies. PMID- 17852881 TI - WITHDRAWN: Peroxisome proliferator-activated receptor gamma Plo12Ala polymorphism influences the susceptibility of a Japanese population to gastric cancer. AB - Objective. Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) has been shown to inhibit the proliferation of gastric cancer (GC) cells and suppress gastric mucosal inflammation induced by Helicobacter pylori infection. The Plo12Ala polymorphism affects codon12 of the PPARgamma gene and alters its promoter activity. The aim of this study was to investigate the influence of PPARgamma gene Plo12Ala polymorphism on the occurrence of (GC) and on the severity of H. pylori-induced gastritis in a Japanese population. Material and methods. The study included 215 patients with GC and 201 patients without GC as a control group. Plo12Ala polymorphism of PPARgamma was investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in all of the subjects. The gastritis score of non-cancerous antral mucosa was calculated by the updated Sydney system. Results. The Plo12Ala genotype of PPARgamma had a significantly higher frequency in GC patients than in controls (OR = 2.43; 95% CI = 1.04-5.67). The Plo12Ala genotype was associated with an increased risk of non-cardiac GC (OR = 2.39; 95% CI = 1.02-5.65), lower-third GC (OR = 3.56; 95% CI = 1.31-9.71), advanced cancer (OR = 2.93; 95% CI = 1.13-7.58), and Lauren's intestinal cancer (OR = 2.94; 95% CI = 1.13-7.66). Among 151 GC subjects, the atrophy and metaplasia scores of the antral mucosa adjacent to cancer tended to be higher in those with the12Ala allele. Conclusions. Our data suggest that the 12Ala allele of PPARgamma may be associated with gastric mucosal atrophy in H. pylori-infected patients, and could increase the risk of GC in the Japanese population. PMID- 17852883 TI - Avenins from different cultivars of oats elicit response by coeliac peripheral lymphocytes. AB - OBJECTIVE: The avoidance of oats in coeliac patients is still controversial. If oats is confirmed to be safe, it would be a valuable component and offer more variation in a gluten-free diet. The aim of this work was to evaluate whether avenins from different varieties of oats show different abilities in the activation of coeliac peripheral lymphocytes. MATERIAL AND METHODS: In order to assess whether the immunogenic effect of oats varies according to the cultivar, peripheral lymphocytes from 10 coeliac children were exposed to avenins from four different oats varieties: Lampton, Astra, Ava and Nave. Lymphocyte proliferation and interferon-gamma (IFN-gamma) release in the culture medium were measured as indexes of immune activation. RESULTS: All the varieties of oats tested were immunogenic, with Lampton and Ava avenins inducing lymphocyte activation similar to that activated by wheat gliadin, while Astra and Nave avenins showed less immunogenicity, but still with a measurable effect. CONCLUSIONS: There are still concerns about the suitability of including oats in a gluten-free diet. Coeliac patients consuming oats-containing food should be carefully monitored, until there is more evidence to show the safety of oats and varieties of low-toxicity oats. PMID- 17852882 TI - Gastrointestinal stromal tumors of the rectum: Clinical, pathologic, immunohistochemical characteristics and prognostic analysis. AB - OBJECTIVE: To describe the clinical, pathological and immunohistochemical characteristics of rectal gastrointestinal stromal tumors (GISTs) and to correlate them with clinical outcomes. MATERIAL AND METHODS: A retrospective review of 29 patients with surgically treated rectal GISTs during the period from 1997 to 2005 was undertaken. The NIH (National Institute of Health Consensus) criteria were applied. RESULTS: All the rectal GISTs in our series originated in the lower half of the rectum and patients underwent primary surgery for complete resections; High-risk, intermediate-risk, low-risk and very low-risk GISTs were found in 11, 6, 5 and 7 patients, respectively. Necrosis, adjacent (mucosal or serosa) invasion and marked pleomorphisms were found in 10, 7 and 20 patients, respectively. Positive expression of CD117, CD34, SMA and S-100 was found in 28, 28, 7 and 3 patients, respectively. Twelve patients had recurrence or metastasis within the median disease-free survival time of 41 months. Among the patients who underwent local resections, the recurrence rate for low-risk and very low-risk GISTs was only 1/10; for intermediate-risk and high-risk GISTs, the recurrence rate after local resections was 3/4, which was higher than the recurrence and metastasis rate of 8/13 after laparotomy. Of the 12 patients with adverse outcomes, 4 patients underwent secondary complete resections; however, all 4 patients had further recurrences. On univariate analysis, risk classification (p = 0.0002), necrosis (p = 0.0205), adjacent invasion (p = 0.0090) and marked pleomorphism (p = 0.0480) were significant predictors of disease-free survival. In the Cox regression model, only the risk classification (p = 0.012) was found to be an independent factor. CONCLUSION: We found that rectal GISTs arise predominantly in the lower half of the rectum and have high CD117 and CD34 expression. Local resection may be a good choice for very-low-risk and low-risk GISTs, but aggressive surgery may be more beneficial for high-risk and intermediate-risk GISTs. For patients with disease recurrence, the results of secondary surgery were poor. Only the NIH risk classification proved to be an independent prognostic factor for rectal GISTs, whereas the proof for other factors was insufficient. PMID- 17852884 TI - Value of routine clinical tests in predicting the development of infected pancreatic necrosis in severe acute pancreatitis. AB - OBJECTIVE: Fine-needle aspiration (FNA) is the procedure of choice for accurate diagnosis of infected necrosis. However, invasive procedures increase the risk of secondary pancreatic infection and the timing of FNA is still a matter for debate. Our objective was to assess the value of routine clinical tests to determine the minimal risk for infected necrosis, thereby optimizing timing and selection of patients for image-guided FNA. MATERIAL AND METHODS: This prospective, non-randomized study comprised 90 patients with acute necrotizing pancreatitis. The data of 52 patients were used for discriminant function analysis to determine the differences between patients with infected necrosis and those with sterile necrosis. Cut-off points for variables were established using receiver operating characteristic (ROC) curve analysis and logistic regression was performed to determine the risk of infected necrosis. The clinical relevance of the defined diagnostic system was prospectively tested in a further 38 consecutive patients with acute necrotizing pancreatitis (ANP). RESULTS: Discriminant function analysis showed that C-reactive protein (CRP) and white blood cell (WBC) values were significant discriminators between patients with sterile necrosis and those with infected necrosis. Cut-off values of 81 mg/l for CRP and 13 x 10(9)/l for WBC were established. The predicted risk for infected necrosis is approx. 1.4% if both tests are below the defined cut-off values. Consequently, we found FNA unnecessary in this subset of patients, unless otherwise indicated, as this invasive procedure per se carries a certain risk of bacterial contamination. CONCLUSIONS: Routine clinical tests are helpful in diagnosing the development of infected necrosis. Based on the application of classification functions, the timing and selection of patients for image-guided FNA can be optimized. PMID- 17852885 TI - Early inflammatory response in acute pancreatitis is little affected by body mass index. AB - OBJECTIVE: Obesity is a known risk factor for severe acute pancreatitis (AP), but the mechanism by which it affects the severity of AP is not fully understood. The main objective of this study was to investigate the relationship between obesity and inflammatory markers in AP. MATERIAL AND METHODS: Thirty patients with AP who developed organ failure (Group I) and 87 patients with AP who survived without organ failure (Group II) were studied. Patients' height and weight were measured at admission for calculation of body mass index (BMI). Blood samples were taken at admission for measurement of plasma interleukin (IL)-1beta, IL-6, IL-10, IL-1 receptor antagonist, procalcitonin, C-reactive protein (CRP) and monocyte human leucocyte antigen (HLA)-DR expression. RESULTS: Group I patients had higher BMI values (median 26.2 kg/m2) than Group II patients (25.2 kg/m2), p =0.033. Both CRP values and monocyte HLA-DR expression showed a significant correlation with BMI (Spearman's rank correlation r=0.32, p =0.003 and r= -0.33, p = 0.002, respectively). The correlation between BMI and monocyte HLA-DR expression was significant in Group II patients (r = -0.34, p =0.002) but not in Group I patients (r = -0.02, p >0.05). There was no correlation between BMI and IL-1beta, IL-6, IL-10, IL-1 receptor antagonist or procalcitonin. CONCLUSIONS: BMI did not affect either proinflammatory or anti-inflammatory cytokine levels in early AP. However, in patients with mild AP, BMI correlated positively with CRP levels and inversely with monocyte HLA-DR expression, which might reflect an amplified inflammatory response in these patients. Taken together, acute inflammatory response in AP, which ultimately determines the severity of AP, was little affected by BMI. PMID- 17852886 TI - Atypical clinical presentation of laboratory-acquired meningococcal disease. AB - We report a case of laboratory-acquired meningococcal disease in a 31-y-old female research assistant. The clinical presentation of the case was atypical with polyserositis affecting knees, pleura and pericardium, without septicaemia or meningitis. The diagnosis was made by positive PCR for Neisseria meningitidis (genogroup C, genosubtype P1.7, 16, 35 and without mutations of the penA gene) in the patient's right knee. Serology confirmed the diagnosis after recovery. This case had an atypical clinical picture, exemplifies the use of non-culture methods for diagnosis and characterization, and reminds us about the importance of safe routines for the laboratory work. PMID- 17852887 TI - Propionibacterium endocarditis: a case series from the International Collaboration on Endocarditis Merged Database and Prospective Cohort Study. AB - Propionibacterium species are occasionally associated with serious systemic infections such as infective endocarditis. In this study, we examined the clinical features, complications and outcome of 15 patients with Propionibacterium endocarditis using the International Collaboration on Endocarditis Merged Database (ICE-MD) and Prospective Cohort Study (ICE-PCS), and compared the results to 28 cases previously reported in the literature. In the ICE database, 11 of 15 patients were male with a mean age of 52 y. Prosthetic valve endocarditis occurred in 13 of 15 cases and 3 patients had a history of congenital heart disease. Clinical findings included valvular vegetations (9 patients), cardiac abscesses (3 patients), congestive heart failure (2 patients), and central nervous system emboli (2 patients). Most patients were treated with beta-lactam antibiotics alone or in combination for 4 to 6 weeks. 10 of the 15 patients underwent valve replacement surgery and 2 patients died. Similar findings were noted on review of the literature. The results of this paper suggest that risk factors for Propionibacterium endocarditis include male gender, presence of prosthetic valves and congenital heart disease. The clinical course is characterized by complications such as valvular dehiscence, cardiac abscesses and congestive heart failure. Treatment may require a combination of medical and surgical therapy. PMID- 17852888 TI - Prevalence of Campylobacter jejuni and enteric bacterial pathogens among hospitalized HIV infected versus non-HIV infected patients with diarrhoea in southern India. AB - A prevalence study on Campylobacter jejuni and other enteric bacterial pathogens was carried out in 200 HIV infected and 200 non-HIV infected subjects with diarrhoeal symptoms at an AIDS Hospital in southern India. Diarrhoeal specimens were inoculated onto standard culture media as well as onto Columbia and Campylobacter blood agar media for C. jejuni isolation. All the C. jejuni isolates were tested for antimicrobial susceptibility using Kirby-Bauer's method. A significant difference in recovery rates was observed between the 2 groups in relation to C. jejuni (p < or = 0.02; 95% CI 5.5 (1-10) and Shigella spp. (p < or = 0.02; 95% CI 6.5 (1-12). 21 isolates of Shigella spp., 16 C. jejuni, 5 Salmonella typhi, 3 Arcobacter spp., 3 Yersinia enterocolitica, and 2 Aeromonas hydrophila were recovered from the HIV infected cases. All the C. jejuni isolates were sensitive to ciprofloxacin whereas 1 strain was resistant to nalidixic acid. Interestingly, all the 29 Shigella spp. (21 from HIV and 8 from non-HIV cases) were resistant to erythromycin and most were resistant to many other antibiotics used. Our observations underline the need for epidemiological investigations to screen C. jejuni and Shigella spp. in HIV infected subjects with diarrhoea and analyse their antibiograms periodically to minimize disease burden in HIV/AIDS. PMID- 17852889 TI - Consequences of inappropriate initial empiric parenteral antibiotic therapy among patients with community-acquired intra-abdominal infections in Spain. AB - To assess the association between inappropriate antibiotic therapy and clinical outcomes for complicated community-acquired intra-abdominal infections in Spain, patient records from October 1998 to August 2002 in 24 hospitals were reviewed. Initial empiric therapy was classified appropriate if all isolates were sensitive to at least 1 of the antibiotics administered. Multivariate analyses were performed to assess associations between appropriateness of therapy and patient outcomes. Healthcare resource use was measured as hospital length of stay (LOS) and d on intravenous antibiotic therapy. A total of 425 patients were included. Of these, 387 (91%) received appropriate initial empiric therapy. Patients on inappropriate therapy were less likely to have clinical success (79% vs 26%, p<0.001), more likely to require additional antibiotic therapy (40% vs 7%, p<0.01) and more likely to be re-hospitalized within 30 d of discharge (18% vs 3%, p<0.01). Multivariate analyses also showed that inappropriate therapy was associated with an almost 16% increase in LOS (p<0.05) and 26% in d of intravenous antibiotic therapy compared with appropriate therapy (p<0.05). Inappropriate initial antibiotic therapy was associated with a significantly higher proportion of unsuccessful patient outcomes (including death, re operation, re-hospitalization or additional parental antibiotic therapies), increased length of stay and length on therapy. PMID- 17852890 TI - Bartonella henselae in the human environment in Poland. AB - The aim of the study was to determine the occurrence of Bartonella henselae reservoir and vectors of infection in the close surroundings of human beings in urban areas of central Poland. The study included mammals (54 dogs, 137 cats) and 102 adult Ixodes ricinus ticks removed from cats and dogs. Blood samples were drawn from each animal and cultured on chocolate agar plates and in mouse fibroblasts L-929 cell line culture. The levels of Bartonella henselae IgG antibodies were determined by indirect immunofluorescence assay. Bartonella spp. strains were isolated from blood of 14 cats (10.2%). Isolates were identified by PCR methods as: B. henselae (18), B. clarridgeiae (1). Blood samples from dogs were consistently negative for Bartonella spp. 59 (45.0%) of 131 tested cats had B. henselae antibodies. B. henselae antibodies were present in 50% of tested dogs, although mostly (96.2%) in low titres 50 y of age. Recommending preventative measures, including vaccination against TBE, to individuals who reside in or regularly visit TBEV endemic areas is suggested. PMID- 17852897 TI - Candidaemia and risk of intraocular infection: a Danish hospital-based cohort study. AB - Intraocular infection is a feared complication in patients with candidaemia. We therefore assessed the current risk and prognosis in Danish candidaemia patients. Candidaemia patients at a Danish university hospital were identified prospectively during a 10-y period, 1995-2004, and ophthalmologic records were retrieved retrospectively. Among 203 incident cases of candidaemia, 86 (42%) were examined at least once by an ophthalmologist. Nine patients had retinitis and 1 patient had endophthalmitis; eye involvement was bilateral in 8 and monocular in 2 patients. Lesions were generally mild and progression was observed in only 1 patient. Surgical treatment was not indicated and the median duration of systemic antifungal therapy was 19 d. The median survival time was 77 d for candidaemia patients with eye involvement, 480 d in candidaemia patients without such an involvement, and only 9 d in candidaemia patients without an ophthalmologic examination. In conclusion, the cumulative rate of intraocular infection was 11.6%, but we suspect an underestimation due to the circumstances of the eye examinations and the rapid death of many patients. We continue to recommend eye examinations for candidaemia patients, but timing seems not to be critical if overt signs of infection are absent, thereby facilitating the use of improved diagnostic methods. PMID- 17852898 TI - Risk factors and outcomes of bloodstream infections with metallo-beta-lactamase producing Acinetobacter. AB - The spread of Gram-negative bacilli with acquired metallo-beta-lactamase (MBL) threatens the successful treatment of major nosocomial infections. The objective of this study was to evaluate the differences in the clinical characteristics of bacteremia caused by MBL-producing Acinetobacter species and MBL non-producing isolates. Two retrospective case-control studies were conducted using data on patients with Acinetobacter bacteremia, who were admitted between January 2001 and December 2005 at a 1500-bed, tertiary-care teaching hospital. Case group 1 (n=27) included patients from whom imipenem-resistant Acinetobacter was isolated in blood culture, and case group 2 (n=7) consisted of those patients from group 1 who yielded MBL-producing isolates. The control group (n=41) included patients from whom carbapenem-susceptible Acinetobacter isolates were isolated in blood culture. Multivariate analysis revealed that the independent risk factors for imipenem-resistant Acinetobacter bacteremia were neutropenia and prolonged use of carbapenem. The independent risk factors for MBL-producing Acinetobacter bacteremia were neutropenia and prolonged use of cephalosporins. The results of this study suggest that a prolonged use of cephalosporins may be associated with MBL-producing Acinetobacter bacteremia. PMID- 17852899 TI - Long-term use of daptomycin for MRSA osteomyelitis and joint infection. AB - This case describes almost continual daptomycin use for approximately 18 months in a patient with osteomyelitis caused by methicillin-resistant Staphylococcus aureus. The case is notable for only a brief episode of myalgia-associated creatine kinase elevations, which quickly resolved. Daptomycin demonstrated efficacy against this strain, which was tolerant to other antibiotics. PMID- 17852900 TI - In-hospital mortality of infective endocarditis: prognostic factors and evolution over an 8-year period. AB - Infective endocarditis (IE) remains severe. Few predictors of prognosis have been identified. It is not known whether mortality of IE has decreased during recent decades. 559 definite cases of IE were collected in a prospective population based survey in 1999 in France. In-hospital death rate was 17%. It was lower in operated patients (14.4% vs 19.3%), although not significantly so. In multivariate analysis, the following variables were independent and significant predictors of mortality: history of heart failure (odds ratio: 2.65), history of immunosuppression (OR: 3.34), insulin-requiring diabetes mellitus (OR: 7.82), left-sided IE (OR: 1.97), heart failure (OR: 2.19), septic shock (OR: 4.33), lower Glasgow coma scale score (OR: 4.09), cerebral haemorrhage (OR: 9.46), and higher C-reactive protein level (OR: 2.60). Adjusted mortality was significantly lower in 1999 than in 1991 (22%): OR: 0.64 (p = 0.03). Thus, in a large and unselected cohort of patients hospitalized for IE in 1999, in-hospital mortality rate was lower than in 1991. Multivariate analysis identified factors classically known as having an impact on mortality. However, other factors, such as age and responsibility of Staphylococcus aureus, were not retained in the model. PMID- 17852901 TI - Clinical evaluation of the recombinant 38 kDa protein of Mycobacterium tuberculosis. AB - The diagnosis of tuberculosis remains among public health concerns due to shortcomings of the purified protein derivative (PPD). Recombinant truncated 38 kDa protein (rTPA38) of Mycobacterium tuberculosis was evaluated to screen new tuberculosis-specific tuberculin. 539 patients, 1133 healthy controls, and 55 guinea pigs were recruited to assess their sensitivity and specificity to rTPA38; 221 healthy controls, with negative responses to rTPA38 and PPD, were vaccinated with M. bovis BCG to determine their cross-reactions with M. bovis BCG. The Mantoux technique was adopted to perform skin tests. No difference in the sensitivity of skin tests was detected between rTPA38 and PPD (78.2% vs 83.4%), but there was a significant difference in the specificity of skin tests between rTPA38 and PPD (75.2% vs 47.0%). Compared to PPD, rTPA38 elicited low positive responses for those recruitments vaccinated with M. bovis BCG. The rTPA38 had significant skin reactions in M. tuberculosis-sensitized guinea pigs, and the opposite was true for both M. fortuitum- and M. kansasii-sensitized guinea pigs. These findings indicate that rTPA38 may have potential as a tuberculosis-specific skin test antigen. PMID- 17852902 TI - Home sampling and pooling of vaginal samples are effective tools for genetic screening of Chlamydia trachomatis among high school female students in Lithuania. AB - The aims were 1) to estimate the prevalence of C. trachomatis infection among sexually active female students in Kaunas, Lithuania; 2) to investigate the usefulness of personal invitation, self-sampling, and pooling of samples for screening; and 3) to evaluate the costs of the approaches used. A cross-sectional study inviting 795 female students (18-31 y of age) from 7 high schools and 1 college in Kaunas was performed. The response rate was 67% (533/795). Self obtained vaginal samples were analysed, individually and pooled (n = 3), using Digene Hybrid Capture II CT/NG Test. The overall prevalence of C. trachomatis infection was 5.6%. Among the sexually active female students 20-24 y of age (n = 424), the prevalence was 7.1%; however, the prevalence varied from 0% to 14.2% at the different schools. For estimation of the population prevalence based solely on identification of C. trachomatis positive pools, the pooling strategy reduced the costs by 85%. For estimation of population prevalence and for diagnosis of each individual sample, pooling reduced the costs by 70%. Targeted screening, using pooling to reduce the expenses, mainly of 3rd and 4th y Lithuanian female students could be recommended. By extended personal contact and internet-based communication, increased participation rates may be attained. PMID- 17852903 TI - Severe Actinobacillus ureae meningitis in an immunocompromised patient: report of one case and review of the literature. AB - 27 cases of Actinobacillus ureae infections including 14 cases of meningitis have been reported. We describe 1 case of Actinobacillus ureae meningitis in a 75-y old patient. Risk factors, clinical outcome and treatment of Actinobacillus ureae infections are discussed. Actinobacillus ureae may behave as an opportunistic pathogen causing severe infections in immunocompromised patients. PMID- 17852904 TI - Is hospital-in-the-home (HITH) treatment of bacterial endocarditis safe and effective? AB - Although serious infections such as bacterial endocarditis (BE) are being increasingly treated with parenteral antibiotics via Hospital-in-the-Home (HITH) programmes in Australia, there are few published data to confirm the safety and efficacy of this treatment modality, especially among patients with BE due to pathogens other than streptococci. In a 12-month prospective, multi-site study we assessed HITH treatment outcomes for all cases of BE. Among the 40 BE cases (29 'definite', 11 'possible'; Duke criteria) caused by a range of pathogens (16 staphylococci spp., 11 streptococci, 4 other, 9 culture-negative), cure was achieved in 37 (93%) cases. BE due to Staphylococcus aureus was significantly associated with an inferior outcome (p =0.046). Adverse events were relatively common (9/40), but most were not severe and were managed with continuation of HITH care. BE can be safely managed via HITH, but particular care in patient selection is necessary, especially for cases due to S. aureus. PMID- 17852905 TI - Seroprevalence of Rickettsia spp. infection among tick-bitten patients and blood donors in Sweden. AB - Serum samples from 236 Swedish patients with symptoms of infectious disease appearing after a tick bite were analysed for the presence of antibodies to Rickettsia helvetica, the only rickettsial species so far isolated from ticks in Sweden. Of these subjects, 137 had tested seropositive for Borrelia burgdorferi. For control purposes, sera from 161 healthy blood donors were examined. A total of 10/397 samples (2.6%) showed IgG-antibodies to R. helvetica at or above a titre of 1/80 as cut-off. 6/137 (4.4%) belonged to the Borrelia positive group, 3/99 (3.0%) to the tick-bitten but Borrelia negative group and 1/161 (0.6%) to the control group. The difference between the tick-exposed groups and the control group was significant in Pearson's 2-sided chi(2) test. In 1 serum sample the presence of antibodies to R. helvetica was further confirmed by Western immunoblot. The study shows that infection with Rickettsia spp. as well as coinfection with Lyme borreliosis needs to be considered in the diagnosis of tick transmitted infections in Sweden. Owing to a known occurrence of immunological cross-reactivites, however, the results must be cautiously interpreted with regard to species of Rickettsia involved. PMID- 17852906 TI - Biofilm formation of the pathogens of fatal bacterial granuloma after trauma: potential mechanism underlying the failure of traditional antibiotic treatments. AB - The pathogen of a new type of disease - fatal bacterial granuloma after trauma (FBGT) - was found to be Propionibacterium acnes (P. acnes). Although in vitro studies showed that the pathogenic P. acnes are sensitive to conventional antibiotics, treatments of FBGT patients with these antibiotics were ineffective. The underlying mechanisms were not clear. Since P. acnes are able to form biofilm on orthopaedic biomaterials in vitro, and pathogenic P. acnes of acnes vulgaris was known to form biofilm in vivo, we hypothesize that the pathogens of FBGT are also able to form biofilm during the pathogenesis, which may be 1 of the reasons for antibiotics tolerance of FBGT. Biofilm forming capacity of the pathogens of FBGT were examined with XTT reduction method, as well as with scanning electron microscope. The effect of long-term subminimal inhibitory concentration (MIC) lincomycin on the biofilm forming ability of the pathogens was also tested. Our results show that both the type strain (NCTC737) and the pathogenic P. acnes of FBGT can form biofilm in vitro. These data demonstrated the biofilm formation of the FBGT pathogens in vitro, and its acceleration by lincomycin, which may be 1 of the major mechanisms for the failure of antibiotic treatment. PMID- 17852907 TI - TBscore: Signs and symptoms from tuberculosis patients in a low-resource setting have predictive value and may be used to assess clinical course. AB - We developed a clinical score to monitor tuberculosis patients in treatment and to assess clinical outcome. We used the WHO clinical manual to choose signs and symptoms, including cough, haemoptysis, dyspnoea, chest pain, night sweating, anaemia, tachycardia, lung-auscultation finding, fever, low body-mass index, low mid-upper arm circumference giving patients a TBscore from 0 to 13. We validated the score with data from a cohort of 698 TB patients, assessing sensitivity to change and ability to predict mortality. The TBscore declined for 96% of the surviving patients from initiation to end of treatment, and declined with a similar pattern in HIV-infected and HIV-uninfected patients, as well as in smear negative and smear positive patients. The risk of dying during treatment increased with higher TBscore at inclusion. For patients with a TBscore of >8 at inclusion, mortality during the 8 months treatment was 21% (45/218) versus 11% (55/480) for TBscore <8 (p< 0.001). TBscore assessed at end of treatment also strongly predicted subsequent mortality. The TBscore is a simple and low-cost tool for clinical monitoring of tuberculosis patients in low-resource settings and may be used to predict mortality risk. Low TBscore or fall in TBscore at treatment completion may be used as a measure of improvement. PMID- 17852908 TI - Outcome of aortic homograft implantation in 24 cases of severe infective endocarditis. AB - The objective of the study was to evaluate the results of treatment of severe aortic endocarditis with an aortic homograft (an aortic valve and root from a donor) in combination with antibiotic therapy. 24 patients with either aortic prosthetic valve endocarditis (n=16) or severe aortic native valve endocarditis (n=8) with destruction of 1 or more cusps, paravalvular abscess formation and/or cardiac fistulas caused by aggressive bacteria, underwent surgery in 1997-2006. Staphylococcal species were the most common pathogens followed by streptococci. Intravenous antibiotic therapy was started before surgery and continued for at least 4-6 weeks. Three patients with prosthetic valve endocarditis died within the first 24 h after surgery from heart failure. Two of these patients required an additional implantation of a mitral valve prosthesis. Five patients died from non-cardiac causes within 1-7 y of surgery. Within the follow-up period no patients had relapse of endocarditis, and only 1 episode of recurrent endocarditis in an intravenous drug abuser was registered. In conclusion, an aortic homograft in combination with intravenous antibiotics is an excellent option for treatment of severe aortic endocarditis. PMID- 17852909 TI - Acute Q fever: an emerging and endemic disease in southern Taiwan. AB - Acute Q fever is a worldwide zoonosis caused by Coxiella burnetii infection. In Taiwan, cases of acute Q fever increased during 3 y of observation, especially at Kaohsiung County and City in southern Taiwan. From 15 April 2004 to 15 April 2007, a total of 67 cases of acute Q fever were identified at E-Da hospital located at Kaohsiung County. 19 (28.4%) patients had a history of travel in rural areas and only 1 had been outside southern Taiwan. 21 (31.3%) patients had a history of animal contact. 20 (30.8%) of the 65 examined patients had underlying chronic hepatitis B or hepatitis C virus infection. Fever (98.5%), chills (79.1%), headache (79.1%), relative bradycardia (44.8%), elevated aminotransferases (100%), and thrombocytopenia (74.6%) were common manifestations. 12 (19.0%) cases had abnormal findings on chest X-ray. Fatty liver (50.0%) and hepatomegaly and/or splenomegaly (41.9%) were found by abdominal image examinations. 42 (76.4%) of 55 cases had defervescence within 3 d after treatment, whereas 4 (7.3%) had spontaneous remission. Acute Q fever is an endemic infectious disease with hepatitis rather than pneumonia as the major presentation in southern Taiwan and the emergence of Q fever is due to increased alertness for the disease by physicians. PMID- 17852910 TI - Herpes simplex virus type 2 infections of the central nervous system: A retrospective study of 49 patients. AB - Herpes simplex virus type 2 (HSV-2) infections of the central nervous system (CNS) are rare with meningitis as the most common clinical presentation. We have investigated the clinical spectrum of CNS infections in 49 adult consecutive patients with HSV-2 genome in the cerebrospinal fluid (CSF). HSV-2 in the CSF was determined by polymerase chain reaction (PCR), and patients were diagnosed as encephalitis or meningitis according to predefined clinical criteria by retrospective data information from consecutive clinical journals. The annual crude incidence rate of HSV-2 CNS disease was 0.26 per 100,000. 43 (88%) had meningitis of whom 8 (19%) had recurring lymphocytic meningitis. Six patients (12%) had encephalitis. 11 of 49 patients (22%) had sequelae recorded during follow-up. None died as a result of HSV-2 CNS disease. Thus, the clinical presentation of HSV-2 infection of the CNS is mainly meningitis but encephalitis does occur and neurological sequelae are common. Recurring lymphocytic meningitis is associated with reactivation of HSV-2 and the condition might be underdiagnosed. PMID- 17852911 TI - Incidence and risk factors for surgical infection after total knee replacement. AB - Surgical site infection (SSI) after total knee replacement (TKR) is a devastating complication. We performed a retrospective study of all consecutive TKRs performed during a 2-y period. Surgical site infection (SSI) was defined by standard criteria. All patients were examined 1 y following surgery. Of 180 patients undergoing TKR, 10 (5.6%) developed a superficial (3, 1.7%) or deep (7, 3.9%) SSI. Two independent risk factors for SSI were detected: left knees became infected more often (9/ 92, 9.8%) than right knees (1/88, 1.1%) (Relative Risk 6.7 +/- 95% CI 1.7-26.8); and 7/72 (9.7%) patients receiving a type-1 prosthesis developed infection versus 3/104 (3.1%) receiving a type-2 prosthesis (RR 4.7, 95% CI 1.18-18.4). Investigation of the operating room revealed 3 problems: there was significant traffic through the door on the left of the patient; a nonstandard horizontal-flow air conditioner had been installed above that door; a tool-washing sink was in use on the other side of that door. Infection control guidelines were rehearsed: the sink was removed, the air conditioner was disconnected, and the door was locked. In a prospective survey performed 2 y later only 1/45 patients (2.2%) undergoing TKR developed a superficial SSI (p = 0.5). Correction of independent risk factors for infection following TKR led to a decrease in SSI rate. PMID- 17852912 TI - Burkholderia pseudomallei: in vitro susceptibility to some new and old antimicrobials. AB - The treatment of melioidosis currently involves the use of antimicrobials such as ceftazidime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate and doxycycline. Evaluation of other antimicrobials with activity against the organism continues to be pursued, however, as the causative organism, B. pseudomallei, may not always be susceptible to the above antimicrobials. This study aimed to test the susceptibility of Malaysian isolates of B. pseudomallei against imipenem, meropenem, ertapenem, moxifloxacin and azithromycin. 80 previously stocked clinical isolates collected between 1978 and 2003 from the UMMC, Kuala Lumpur were tested for in vitro susceptibility to these antimicrobials using the E-test minimum inhibitory concentration method. 100% of isolates were sensitive to imipenem and meropenem, 97.5% were sensitive to trimethoprim-sulfamethozaxole, 37.5% to moxifloxacin, and only a minority was sensitive to ertapenem (7.5%). Using breakpoints for Staphylococcus and Haemophilus, 5.0%-6.3% of isolates were sensitive to azithromycin. In conclusion, our findings support the in vitro efficacy of imipenem, meropenem and trimethoprim-sulfamethoxazole against B. pseudomallei. Moxifloxacin, ertapenem and azithromycin cannot be recommended for the treatment of melioidosis; however, further studies are needed to test the efficacy of azithromycin in combination with quinolones. PMID- 17852913 TI - Clinical presentation of adults with pulmonary tuberculosis with and without HIV infection in Nigeria. AB - Our aim was to describe the frequency of HIV infection among patients with tuberculosis and compare their characteristics with patients with TB but not infected with HIV. Patients with cough >3 weeks duration attending 8 hospitals in Abuja, Nigeria were screened with smear microscopy and culture and tested for HIV. Chest X-rays were graded by 2 readers. 731 (62%) of 1186 patients had positive cultures and 353 (48%) of these 731 patients were smear positive. 1002 (85%) patients were tested for HIV and 546 (55%) were positive. 53% (329/625) of the culture positive patients and 58% (217/377) of the culture negative patients were HIV positive. Anorexia, weight loss, low BMI (<18.5), haemoglobin (<11 gm/dl) and albumin and high ESR and liver enzymes were more frequently observed among patients with TB coinfected with HIV than in patients without HIV. Coinfected patients had less cavitations and lung involvement on X-rays than patients without HIV. In conclusion, the prevalence of HIV is very high among patients with TB in Abuja, Nigeria. The presence of HIV decreases the sensitivity of smear microscopy and complicates the diagnosis of TB. Selected clinical and laboratory parameters could be used to identify individuals with TB who are likely to be coinfected with HIV. PMID- 17852914 TI - Clonal diversity of Salmonella enterica serotype Typhi isolated from patients with typhoid fever in Tehran. AB - In this study, antimicrobial susceptibility test and genetic typing were used to characterize 15 Salmonella enterica serotype Typhi (S. Typhi) isolates recovered from sporadic cases of typhoid fever in Tehran, Iran during 2004. Antimicrobial susceptibility test showed that all isolates were susceptible to 20 antimicrobials examined in this study. Analysis of insertion elements showed that 2 IS200 types with 10 and 11 copies were present. 11 of the 15 isolates were found to possess 10 IS200 elements residing on fragments from 23 to 2.3 kb. Comparison of the RiboPrinter (automated ribotyping) patterns of S. Typhi showed that 60% (9/15) of the isolates belonged to a single ribotype. PCR based random amplified polymorphic DNA analysis (RAPD) and enterobacterial repetitive intergenic consensus (ERIC) and pulsed-field gel electrophresis (PFGE) were also performed. ERIC and RAPD-PCR method showed 2 and 3 genotyping patterns amongst the isolates, respectively. The PFGE typing was carried out by using XbaI restriction enzyme, and 7 restriction patterns were observed. Overall, the molecular typing methods applied in this study showed that the isolated S. Typhi populations were highly polyclonal as shown by PFGE. PMID- 17852915 TI - Early diagnosis of tuberculosis using an INF-gamma assay in a child with HIV-1 infection and a very low CD4 count. AB - An 11-y-old girl diagnosed with HIV-1, presented with prolonged pyrexia and a non reactive tuberculin skin test. An INF-gamma assay (ELISpot) was positive and led to administration of tuberculosis treatment. Positive cultures for Mycobacterium tuberculosis followed 6 weeks later. INF-gamma assays should be considered as first line investigations in HIV-1 infected subjects when TB is a diagnostic possibility. PMID- 17852916 TI - Group G Streptococcus spinal epidural abscess: case report and review of the literature. AB - Group G streptococci have been identified as a recently emerging pathogen. Spinal epidural abscess is an infrequent but well described infection of the central nervous system that may present with non-specific clinical symptoms and physical examination findings. Group G streptococci are a rare cause of spinal epidural abscess that should be considered in the clinical picture so that appropriate therapy can be initiated in a timely fashion. PMID- 17852917 TI - Candida albicans masquerading as gram-negative bacilli in the clinical laboratory. AB - We report misidentification of Candida albicans as Gram-negative bacilli owing to colony morphology on MacConkey agar and subsequent inoculation into GN-ID/VITEK 2. ATCC and clinical Candida strains (n = 24) masqueraded as various bacterial species when experimentally inoculated into GN-ID cards. This phenomenon should be considered when peculiar taxa or susceptibility are encountered. PMID- 17852918 TI - HSV presence in the CSF of a head trauma patient: cause or result? PMID- 17852919 TI - Demographics of Giardia infections in Bergen, Norway, subsequent to a waterborne outbreak. AB - Young women have previously been reported as the predominant group infected during a waterborne giardiasis outbreak, due to elevated water consumption. Here, the demographics of those subsequently infected are described, and young women again predominate. As secondary cases were not waterborne, this cannot be attributed to drinking habits. PMID- 17852920 TI - Toxic-febrile neurobrucellosis, clinical findings and outcome of treatment of four cases based on our experience. AB - Central nervous system (CNS) involvement is uncommon in brucellosis. Neurological complications of brucellosis may be divided into 2 major groups: 1) those related to the acute-febrile state that occurs in acute disease (toxic-febrile neurobrucellosis), and 2) those related to actual invasion and localization of the pathogen in the CNS (classical neurobrucellosis). In this paper, we present 4 cases of toxic-febrile neurobrucellosis and discuss clinical findings and outcome of treatment in these cases. All patients had fever, headache, stupor or coma with neuropsychiatric symptoms such as hallucination, delirium, convulsion, dysarthria, psychosis, and night raving. Peripheral and cranial vasculitis was present in case 3 and bilateral sensorioneural hearing loss in case 4. Neither pleocytosis nor hyperproteinorrachia was present in any patient in lumbar puncture. Brucella melitensis was isolated in case 3 from bone marrow, and in case 4 both from blood and bone marrow. All patients received combined treatment consisting of ceftriaxone, rifampicin, and doxycycline. They were discharged from the hospital with full recovery. No recurrence or any complaint was observed during the follow-up. In conclusion, despite the rapid course and serious complications, outcome from febrile-toxic neurobrucellosis is excellent especially when effective antimicrobial therapy is started early in the course of illness. PMID- 17852921 TI - Long term failure of miltefosine in the treatment of refractory visceral leishmaniasis in AIDS patients. AB - We carried out a retrospective and descriptive study of 4 HIV infected patients with relapsing visceral leishmaniasis (VL) seen at 2 tertiary-care hospitals in Spain during the last 6 y, in whom miltefosine was used as a compassionate use treatment at a dosage of 50 mg b.i.d. Patients had a medium CD4 lymphocyte count of 69 cells/microl and were C stage. All patients received at least 2 different anti-leishmanial drugs and had at least 3 relapses before miltefosine treatment (range 3-7). Three patients were treated with miltefosine at a standard dose of 50 mg b.i.d. for 28 d, and the other during 12 months. Despite an initial symptomatic improvement, miltefosine treatment failed to eradicate the infection in all cases. We conclude that the use of miltefosine alone is not strong enough to cure relapsing VL in HIV-1 controlled infected patients. PMID- 17852922 TI - High Bartonella spp. seroprevalence in a Swedish homeless population but no evidence of trench fever. AB - Blood samples and epidemiological data were collected from 50 homeless patients in central Stockholm, Sweden. Sera were analysed for antibodies to B. henselae, B. quintana, B. elizabethae and B. grahamii. Whole blood was cultured and used as substrate for a newly developed quantitative real time polymerase chain reaction (QPCR) specifically targeting Bartonella spp. DNA. 61 matched blood donor sera were used as controls. Homeless patients were significantly more often seropositive to Bartonella spp. than controls (OR 7.58 (3.30-17.39), p<0.05). Reactivity to the B. elizabethae antigen was dominating, although the difference between patients and controls was most significant in seroreactivity to the B. henselae antigen. There was no evidence of an ongoing B. quintana epidemic. The absence of louse infestation could explain the lack of B. quintana bacteraemia and the failure to amplify Bartonella DNA. PMID- 17852923 TI - A longitudinal investigation of Plasmodium falciparum malaria in children in northern India. AB - A group comprising 27 young children (1-4 y of age) suffering from uncomplicated falciparum malaria were studied to characterize the isolates and to measure humoral immune responses during acute infection and after recovery. Finger prick blood from each individual was collected on d 1. After treatment with chloroquine, a further blood sample was collected from each child on d 7, 30, 90 and 180 for assay of antibody responses to P. falciparum antigens. Isolates from individual patients were incubated in vitro for demonstration of rosette formation, assay of plasmodial growth rate and analysis of Pfcrt gene polymorphism. Out of 27 isolates of P. falciparum, 20 showed formation of rosettes in vitro. The growth rate at 96 h varied widely among the isolates. In Pfcrt gene analysis at 76-codon site, 14 showed wild-type Lys 76, 7 showed mutant type Thr 76 and 6 had mixed type. 14 children, all with anaemia on d 7, showed a positive direct antiglobulin test (DAT). Sera positive by ELISA IgG on d 90 also showed parasite growth inhibitory activity in vitro. Significant levels of IgG, IgG1 and IgG3 subclass antibodies against MSP1 were detected in 14 sera collected on d 90. On d 180, there was a decline in IgG and its subtypes. These findings suggest that a variability in isolates may occur in one and the same seasonal area, making children prone to infection. As a consequence, they develop antibodies during recovery phase from an acute attack, which remain in circulation for a period of 4-5 months. After that, a decline in antibody level may again make them susceptible to the disease. Prevalence of different serotypes in a small area may suggest the complexity of malaria transmission. PMID- 17852924 TI - Epidemiology and clinical outcome of candidaemia among Jordanian newborns over a 10-year period. AB - This retrospective study includes all newborn patients with culture proved candidaemia who were admitted to the neonatal intensive care unit of Jordan University Hospital through the period January 1995 to June 2006. Among 24 patients included, 13 (54.2%) died. The incidence of candidaemia was 0.27%, the mean age at diagnosis 25.9 d and the mean gestational age at birth 34.6 weeks. Species most frequently isolated were Candida albicans (50%) and C. krusei (20%). Previous gastrointestinal pathology was present in 41.7% of the cases. A comparison of cases due to C. albicans with those due to other species of Candida revealed no statistical differences in terms of demographic factors, age at onset of disease, mortality, clinical manifestations or risk factors. Based on our results, empirical antifungal therapy should be considered in neonates who have gastrointestinal pathology and other risk factors. PMID- 17852925 TI - Long-term effect on body composition and metabolic parameters after treatment with recombinant human growth hormone (r-hGH) in HIV-1 infected patients with lipodystrophy. AB - Several studies have shown reduction of visceral adipose tissue (VAT) using recombinant human growth hormone (r-hGH) in HIV-1+ patients, but whether these effects are maintained after the end of treatment is unknown. In a prospective, randomized study we previously studied the effects of r-hGH 4 mg daily vs 3 times/week over 12 weeks, followed by a 2 mg daily maintenance dose for an additional 12 weeks. T1 weighted MRI flash sequences were performed of the face, abdomen and at mid-thigh level (MTF) at baseline, week 12, week 24 and at follow up. Of 20 subjects who completed the 24-week study, follow-up is available for 16 patients (15 male, mean age 44.8 y, mean duration of HIV infection 13.5 y). After a median time of follow-up of 9 months, VAT remained overall 18% below baseline level (p =0.005). MTF was significantly reduced by 12% compared to its baseline level (p =0.03). Fasting glucose levels significantly improved by 21% compared to baseline (p =0.006). These results suggest that the achieved reduction of VAT using r-hGH in lipodystrophic HIV+ patients is in part maintained after a median follow-up of 9 months. PMID- 17852926 TI - Invasive candidiasis in long-term patients at a multidisciplinary intensive care unit: Candida colonization index, risk factors, treatment and outcome. AB - The incidence of fungal infections in hospitalized patients has increased, and due to demographic changes and increasingly advanced medical methods, the intensive care units (ICU) have emerged as epicentres for fungal infections. The aim of the present study was to investigate Candida colonization pattern and colonization index (CI), in combination with other risk factors and its relation to invasive candida infection (ICI), in 59 consecutive patients with at least 7 d length of stay (LOS) at a multidisciplinary ICU. Surveillance samples were collected on d 7 and then weekly during the ICU stay. In addition, immunological status was monitored by measuring the histocompatibility leukocyte antigen-DR (HLA-DR). In the present study with a patient population burdened by several risk factors for ICI, 17% acquired an invasive infection. Overall ICU mortality was 30%. We could demonstrate that both a high colonization index and recent extensive gastroabdominal surgery were significantly correlated with ICI, while a decreased level of HLA-DR (< or = 70%) was not predictive for ICI in this high risk population. The results indicate that ICU patients exposed to extensive gastroabdominal surgery would benefit from early antifungal prophylaxis. PMID- 17852927 TI - Urinary tract infection due to Achromobacter xylosoxidans: report of 9 cases. AB - Urinary tract infection (UTI) due to Achromobacter xylosoxidans is rare. The aims were to know the frequency and clinical characteristics of this infection in our area. We performed a retrospective analysis of 9 patients with UTI caused by this organism diagnosed over a period of 13 y. The mean age was 63.1 y. All patients had underlying diseases or urological abnormalities. The most frequent underlying diseases were solid or hematological malignancies (3 cases). Seven patients (77.7%) had urological abnormalities. Eight patients had symptoms of cystitis and 1 remained asymptomatic. Seven patients had community acquired UTIs. Clinical outcome was favourable in 5 patients after antibiotic treatment and recurrence occurred in 3 patients who had urological abnormalities. All isolates were susceptible to imipenem and piperacillin-tazobactam, 88.8% were susceptible to ceftazidime and 77.7% were susceptible to trimethoprim-sulfamethoxazole. High frequencies of resistance to ampicillin (100%), amoxicillin/clavulanic acid (78%), cefuroxime (100%), cefotaxime (67%), norfloxacin (89%), ciprofloxacin (78%), nitrofurantoin (89%) and gentamicin (67%) were observed. UTI due to A. xylosoxidans was predominantly observed in elderly patients with predisposing factors, especially urological abnormalities, malignancies and immunosuppression. Treatment can be difficult due to the high level of antibiotic resistance. Trimethoprim-sulfamethoxazole may be useful for treatment, particularly in outpatients with community acquired infections. PMID- 17852928 TI - Pneumocystis jiroveci pneumonia and other pulmonary infections in TB smear negative HIV-positive patients with atypical chest X-ray in Ethiopia. AB - Pneumocystis pneumonia (PCP) has been considered a rare disease in sub-Saharan Africa. However, a rising prevalence has been noted recently. The objective of this study was to determine the relative prevalence of PCP and other pulmonary opportunistic diseases in patients infected with HIV in Ethiopia. 131 consecutive patients with respiratory symptoms and atypical chest X-ray, who were sputum smear-negative for AFB and seroreactive for HIV, underwent clinical evaluation and investigation for Pneumocystis jiroveci and Mycobacterium tuberculosis from sputum and bronchoalveolar lavage (BAL), and fungal and bacterial pathogens from BAL alone. Bacterial infections, Pneumocystis pneumonia (PCP) and pulmonary tuberculosis (PTB) occurred in 44 (33.6%), 39 (29.7%) and 31 (23.7%) patients, respectively. Pulmonary Kaposi sarcoma and non-specific interstitial pneumonitis occurred in 4 patients each. In a multivariate regression model, predictors of PCP were typical chest X-ray and low CD4 count while purulent sputum predicted bacterial infection. The sensitivity of physicians and chest X-ray diagnosis was particularly low for PTB and bacterial infections. We conclude that chronic bacterial infection and Pneumocystis pneumonia are important differential diagnoses in HIV-infected, smear-negative PTB patients presenting with atypical chest X-ray. We therefore need to escalate the use of preventive and highly active antiretroviral (HAART) treatment in order to prevent a PCP epidemic. PMID- 17852929 TI - A case of meningoencephalitis associated with G1P[8] rotavirus infection in a Japanese child. AB - We report the case of a 2-y, 11-month-old boy with G1P[8] rotavirus infection accompanied by acute meningoencephalitis. Substitutions in both the VP4 and VP7 genes were found in the identified strain. A commonly circulating G1P[8] rotavirus with such mutations might be associated with the pathogenesis of CNS complications, including meningoencephalitis. PMID- 17852930 TI - The use of procalcitonin in the diagnosis of late-onset infection in neonatal intensive care unit patients. AB - We evaluated the semi-quantitative procalcitonin level for diagnosing late-onset infections in 176 neonates. Using a cut-off level of 0.5 ng/ml, the sensitivity was 84.4%+/-0.19, specificity was 93.9%+/-0.04, positive predictive value was 82.6%+/-0.1, and negative predictive value was 94.6%+/-0.04. Procalcitonin could be a useful marker of late-onset infection in neonates. PMID- 17852931 TI - Simkania negevensis may be a true cause of community acquired pneumonia in children. AB - Simkania negevensis, a recently found Chlamydia-like organism, has been associated with bronchiolitis and pneumonia in children. S. negevensis findings have been common also in healthy, non-symptomatic subjects. Antibodies to S. negevensis were measured by microimmunofluorescence in 174 frozen paired sera obtained from children with community acquired pneumonia in a population-based study. There was evidence of S. negevensis infection in 18 (10%) cases. All diagnoses were based on the presence of specific IgM antibodies. The numbers of S. negevensis cases increased from 2 (4%) at <24 months to 7 (15%) at > or = 10 y of age. 12 (67%) were mixed infections with viruses or other bacteria. 16 children (9%) had measurable IgG antibodies to S. negevensis, but significant rises were not found in any cases. Thus, S. negevensis may be a real, though rare, cause of CAP in children, occurring often in mixed infections with viruses and other bacteria. PMID- 17852932 TI - High adherence with a low initial ribavirin dose in combination with pegylated IFN alpha-2a for treatment of recurrent hepatitis C after liver transplantation. AB - Patients with recurrent hepatitis C after liver transplantation often cannot tolerate full dose of pegylated interferon (peg-IFN) and ribavirin (RBV) and are often withdrawn prematurely from treatment. We chose a low initial RBV dose, later increased due to tolerance to a mean dose of 600 mg daily (range 200-1000 mg daily) in combination with a peg-IFN alpha-2a 180 mcg weekly in an effort to improve tolerance and minimize withdrawals. 16 patients with hepatitis C recurrence and 1 with de novo HCV infection with a mean age of 54 y (range 43-66 y), 71% males, were treated. All patients completed the intended treatment schedule 24 weeks for genotype 2 and 3 and 48 weeks for genotype 1 and 4. Early viral response was achieved in 12 (71%), non-response in 1 patient with genotype 4, and sustained viral response in 4/5 (80%) patients with genotype 2 or 3 and 3/11 (27%) with genotype 1, p<0.05. To conclude, we found that utilizing a low initial daily RBV dose, later increased due to tolerance in combination with peg IFN alpha-2a 180 microg weekly, was successful. Hence, all patients completed a full treatment course, which also offered a reasonable efficacy. PMID- 17852933 TI - Assessment of infection control knowledge, attitude and practice among healthcare workers during the Hajj period of the Islamic year 1423 (2003). AB - We assessed hospital infection control knowledge, attitude, and practice (KAP) of healthcare workers (HCWs) during the Hajj season of the Islamic y 1423 (2003). A self-administered structured questionnaire was used to collect the data. A total of 392 HCWs was studied, of whom 215 (54.8%) were nurses and 177 (45.2%) were doctors. 315 (80.4%) HCWs worked in hospitals, whereas 77 (19.6%) worked in primary healthcare centres. Of the 392 HCWs, 164 (41.8%) were from Makkah, and the remaining 228 (58.2%) were recruited from other regions in Saudi Arabia. A good proportion (81.8%) of HCWs correctly answered at least 5 of the 11 knowledge statements. However, obvious deficiency of knowledge appeared concerning other important hospital infection control measures. A smaller proportion (61.9%) of HCWs achieved a score of at least 4 out of 7 for attitude statements with unacceptable attitude for the remaining 3 areas. Response to questions concerning practice showed that nurses tended to be better than doctors (p-value=0.204), but both groups reported variable compliance to hospital infection control practices in terms of strict or near-strict adherence. In conclusion, training of HCWs is needed to improve KAP in infection control. PMID- 17852934 TI - Susceptibility to daptomycin, quinupristin-dalfopristin and linezolid and some other antibiotics in clinical isolates of methicillin resistant and methicillin sensitive S.aureus from the Oslo area. AB - Our study compared the susceptibility of 136 clinical isolates of Staphylococcus aureus and 119 multidrug-resistant Staphylococcus aureus (MRSA) isolates from Oslo to a range of antibiotics, including the novel antibiotics quinupristin dalfopristin, linezolid and daptomycin. All isolates were susceptible to daptomycin, linezolid and quinupristin-dalfopristin, although a subgroup was less susceptible to the latter. There was no linkage between reduced susceptibility to daptomycin, linezolid or quinupristin-dalfopristin and resistance to other classes of antimicrobials. In addition, MRSA strains from 2004 have become more sensitive to fucidin and rifampicin. The results can be used to evaluate the appropriateness of breakpoints and to define a baseline for monitoring possible future emergence of resistance to daptomycin, quinupristin-dalfopristin and linezolid in Staphylococcus aureus in Norway. PMID- 17852935 TI - Staphylococcus aureus colonization among nursing home residents in a large Finnish nursing home. AB - We studied colonization with methicillin-resistant and -sensitive Staphylococcus aureus (MRSA, MSSA) in the second largest nursing home in Finland, in which the residents volunteered had their nostrils, throats, perineums, skin lesions, and catheter exit sites swabbed, and catheter urines cultured. The specimens were cultured onto non-selective and selective agar, with or without enrichment in salt-containing trypticase soy broth (TSB). S. aureus was identified by routine methods, methicillin resistance was detected by oxacillin and cefoxitin disk diffusion and MIC E-tests, and GenoType MRSA -test was used for mecA gene confirmation. A total of 663 cultures were obtained from 213 residents. Of those, 165 specimens (25%) from 94 residents (44%) were positive for S. aureus, and 3 specimens (0.4%) from 2 (0.9%) residents were positive for MRSA. Of the 165 S. aureus isolates, 31 (19%) from 25 (27%) residents were found only from sites other than nostrils (30 MSSA and 1 MRSA). TSB enrichment detected additional 33 (5%) S. aureus isolates (32 MSSA and 1 MRSA), resulting in 8 (5%) additional residents. None of the MRSA strains would have been found if only nostrils and throat had been screened, and no enrichment broth had been used. PMID- 17852936 TI - Fluoroquinolone prescriptions in a teaching hospital: a prospective audit. AB - The aim of this study was to identify prospectively the prevalence of unnecessary or inappropriate fluoroquinolone prescriptions in our teaching hospital and to identify the contributing factors. 55% of the 110 prescriptions evaluated were unnecessary or inappropriate. Ward and combination therapies were significantly associated with misuse. PMID- 17852937 TI - Aetiological diagnosis of community acquired pneumonia: utility of rapid microbiological methods with respect to disease severity. AB - The present study investigated the utility of rapid microbiological methods in the aetiological diagnosis of community acquired pneumonia (CAP) according to the severity of CAP. Between 1999 and 2004, 384 adult patients with CAP were studied prospectively. In addition to standard microbiological methods, PCR and antigen detection techniques were used to identify pathogens. A total of 230 microbial agents in 209 patients were identified, with 134 (58.2%) identified by antigen detection or PCR tests. Of these 134 microbial agents, 95 (70.9%) were identified only by these rapid methods. Streptococcus pneumoniae urinary antigen detection was positive in 24.3% (81/333) of the patients with a diagnostic yield of 38.7% in those with severe pneumonia. Respiratory viral antigen detection was positive in 11.1% (35/314) of the patients with the highest diagnostic yield (20.3%) in patients with severe pneumonia. Mycoplasma pneumoniae PCR was positive in 7.5% (13/174) of the patients, all of whom were low-risk patients. Only 1 case of Chlamydia pneumoniae was identified by PCR. In conclusion, besides yielding the aetiological diagnosis rapidly, new methods add to the total diagnostic yield in CAP. The diagnostic yield of rapid methods differs according to the severity of the pneumonia. PMID- 17852938 TI - Comparison of the VersaTREK system and Lowenstein-Jensen medium for the recovery of mycobacteria from clinical specimens. AB - Laboratory services for the detection of tuberculosis form an essential component of the DOTS strategy. Our objective was to evaluate the recovery rate and mean time to detection (TTD) of mycobacteria of 2 culture media: the VersaTREK system and the Lowenstein-Jensen medium (LJ). Clinical specimens were processed using the standard N-acetyl-L-cysteine (NALC)-NaOH method, and then inoculated onto VersaTREK system and LJ slants. Of 1510 specimens cultured, a total of 200 mycobacterial isolates (159 Mycobacterium tuberculosis and 41 no M. tuberculosis mycobacteria) were detected. The recovery rates were 84.8% (168/198) for the VersaTREK system and 89.4% (168/188) for LJ (p=0.2); while the contamination rates were 4.2% for the VersaSATREK system and 7.4% for LJ (p<0.001). The TTDs for mycobacteria spp. were 18.2 (+/-11.4) d for the VersaTREK system and 27.9 (+/ 10.9) d for LJ (p<0.001). The TTDs for M. tuberculosis were 19.8 (+/-11.2) d for the VersaTREK system and 27.3 (+/-10.2) d for LJ (p<0.001). The difference in TTD between smear-positive and smear-negative specimens for Mycobacterium spp. was 15.9 (+/-10.0) vs 23.0 (+/-12.5) d, and for M. tuberculosis 16.7 (+/-9.5) vs 28.4 (+/-11.1) d for the VersaTREK system. The VersaTREK system significantly reduces the TTDs of mycobacteria detection, which is clinically relevant. PMID- 17852939 TI - Immunological response to hepatitis B vaccination in patients with AIDS and virological response to highly active antiretroviral therapy. AB - Previous studies showed that an immunological response to hepatitis B virus (HBV) vaccination in patients with AIDS was lower than in the normal population. However, those with virological response to highly active antiretroviral therapy (HAART) may have a normal immunological response to HBV vaccination. In our study, patients with AIDS who had a virological response to HAART and no immunity to HBV received 3 doses of HBV vaccine (20 microg of Engerix-B(R)) on d 0, 30, and 180. Anti-HBs level was measured 1 month after complete vaccination. Of 28 patients, overall response rate to vaccination was 71.4%. The responder group had a significantly higher CD4 count at 1 month after complete vaccination than the non-responder group (466.95+/-146.94 and 335+/-112.62 cells/microl, p =0.035). The patients receiving efavirenz-containing HAART had better response than those without efavirenz-containing HAART (p =0.030). The responder group had received a longer duration of HAART. In conclusion , to our knowledge, ours is the first prospective study to determine the immunological response to HBV vaccination in all patients with AIDS who had maintained the virological response after receiving HAART throughout the study period. Patients with AIDS and virological response to HAART have a good immunological response to HBV vaccination. PMID- 17852940 TI - The pharmacokinetic profile of plasma-derived mannan-binding lectin in healthy adult volunteers and patients with Staphylococcus aureus septicaemia. AB - Mannan-binding lectin (MBL) is a member of the innate immune system, and MBL deficiency affects 10-15% of Caucasians. With development of a plasma-derived MBL, substitution has become a therapeutic option in diseases associated with MBL insufficiency. The pharmacokinetics of injected MBL is weakly described, particularly in patients with infectious diseases. The pharmacokinetic profile of MBL following administration of 0.08 mg/kg to 20 healthy MBL-deficient volunteers and 0.2 mg/kg to 2 patients with Staphylococcus aureus septicaemia was established. In the volunteers, the maximal concentration was 2849 microg/l; the mean half-life (T(1/2)) was 69.6 h (14.6-114.9 h). The normalized clearance was 9x10(-6) l/minxkg, and the mean residence time was 82 h. In the patients the serum-MBL versus time curves were similar to those in the volunteers, and T(1/2) values were 36 and 40 h. In conclusion, MBL is distributed into a median volume of 3.4 l similar to the plasma volume, and the elimination in septicaemic patients was within the range of the controls. Due to the large individual variation in T(1/2), we recommend that MBL therapy, with respect to dose and infusion intervals, is based on the chosen therapeutic target (> or =1000 microg/l) and MBL serum determinations following the first infusion. PMID- 17852941 TI - Methicillin-resistant Staphylococcus epidermidis (MRSE) endocarditis treated with linezolid. AB - Linezolid is not yet recognized as a standard therapy for infective endocarditis but its use becomes a necessity when infection is due to multidrug-resistant microorganisms. This report describes 1 patient with endocarditis treated with linezolid and 45 similar cases from the medical literature. PMID- 17852942 TI - Characterization of a new Neisseria meningitidis serogroup C clone from China. AB - This study has verified the spread of ST-7 serogroup C meningococci in China and characterized this new clone using porA typing and comparative genomic hybridization (CGH) analysis. The data would be helpful to monitor the spread of this new serogroup C meningococci sequence type clone in China and worldwide. PMID- 17852943 TI - Serious community-acquired paediatric infections in rural Asia (Bohol Island, Philippines): bacterial meningitis in children less than 5 years of age. AB - This paper describes the clinical profile and aetiology of bacterial meningitis in infants and children less than 5 y old admitted to a rural general hospital in the Philippines. A total of 989 infants and children 0-59 months old with suspected meningitis using a standardized guideline based on clinical signs and symptoms were prospectively enrolled from April 1994 to May 2000. Blood and CSF were drawn on admission for culture, antigen testing and cell count. All had blood cultures and 623 (63%) had CSF samples. Bacterial aetiology was found in 54 (5%). The most common bacterial pathogens were H. influenzae type b (Hib) (20, 37%) and S. pneumoniae (Pnc) (10, 18%). All of the Hib infections and 8 (80%) Pnc infections were in infants less than 1 y old. 12 (22%) of the subjects with bacterial meningitis died. All strains of S. pneumoniae and H. influenzae were sensitive to chloramphenicol, cotrimoxazole and ampicillin. In conclusion, S. pneumoniae and H. influenzae type b are the most common aetiological agents of bacterial meningitis in a rural area in the Philippines, and occur especially in infants less than 1 y old. Aetiological agents were susceptible to the currently recommended antimicrobial agents. PMID- 17852944 TI - Susceptibility of staphylococci and enterococci to antimicrobial agents at different ward levels in four north European countries. AB - A multicentre susceptibility study was performed on staphylococci and enterococci isolated from patients at 3 different ward levels: primary care centres (PCCs), general hospital wards (GHWs) and intensive care units (ICUs), in Denmark, Finland, Norway and Sweden. There was a markedly higher incidence of resistance among CoNS in ICUs compared to GHWs and PCCs. Resistance rates were low among S. aureus isolates and no differences were found between the ward levels. Oxacillin resistance was found among 1.6% of S. aureus and 47% of CoNS isolates. 14% of CoNS and 0.9% of S. aureus isolates were glycopeptide intermediate. The prevalence of E. faecium isolates in this study differed significantly between the ward levels with the lowest prevalence found at PCCs. High level gentamicin resistant (HLGR) enterococci occurred in 11-25% of E. faecium and 6-20% of E. faecalis isolates. The HLGR rate was significantly higher among E. faecalis from hospitalized patients (GHWs and ICUs) compared to patients at PCCs. For enterococcal isolates, no other significant differences in antimicrobial resistance were found between the ward levels. All enterococci were teicoplanin susceptible, but decreased susceptibility to vancomycin was found among 2.0% and 0.6% of the E. faecium and E. faecalis isolates, respectively. PMID- 17852945 TI - Adjunctive steroid treatment: local guidelines and patient outcome in adult bacterial meningitis. AB - Our objective was to evaluate local guidelines regarding early steroid treatment in adult community acquired bacterial meningitis, and assess the actual treatment given and its correlation to clinical outcome. Patient outcome was obtained retrospectively from the medical records of 210 adults admitted to 47 hospitals in Denmark during 2002-2004 (population 5.4 million) and was combined with results from a questionnaire regarding treatment guidelines in these hospitals. In 36 of 47 departments responding to the questionnaire, 21 recommended early steroid treatment, but none did so initially during 2002. Early steroid treatment was given to 15% of patients and was given more often when recommended locally (41% vs 11%, OR=5.7 (2.4-13.5)). Unfavourable outcome was demonstrated rarely in patients treated with early steroids compared to the non-steroid group (17% vs 42%, p<0.05). In the 32 cases with petechial skin lesions, these were caused by pneumococci (15), meningococci (15), Staphylococcus aureus (1) and enterococci (1), and thus the presence of such lesions should not make the clinician abstain from early steroid treatment of bacterial meningitis. In conclusion, concordance with the new consensus of early steroid treatment was poor on a national basis, and better (41%) when adequate local guidelines were available. Early steroid treatment was associated with favourable outcome, and improved implementation of adequate guidelines may contribute to better patient outcome in bacterial meningitis. PMID- 17852946 TI - Investigation of correlation between Toxoplasma gondii IgG positivity and Hs-CRP. PMID- 17852947 TI - Alternate-day versus once-daily administration of amphotericin B in the treatment of cryptococcal meningitis: a randomized controlled trial. AB - Animal studies and case series have demonstrated the dose-dependent efficacy and long half-life of amphotericin B deoxycholate (ABd), providing the rationale for our randomized controlled study to compare once-daily (OD) (1 mg/kg) and alternate-d (AD) (2 mg/kg) administration of ABd in the treatment of cryptococcal meningitis in patients with AIDS hospitalized at King Chulalongkorn Memorial Hospital, Thailand, from 2003 to 2004. Of 28 patients, 15 and 13 received OD and AD administration, respectively. There was no significant difference between the 2 groups regarding the demography, clinical features, and laboratory data. After 2 weeks of the intensive-phase treatment, there was no significant difference in the clinical response between the OD (80%) and AD (76.9%) groups. Mycological response was observed in 33.3% and 10% of patients in the OD and AD groups, respectively (p = 0.3). There was no difference in nephrotoxicity and infusion related events. In conclusion, this is the first randomized controlled study comparing OD and AD administration of ABd in the treatment of cryptococcal meningitis. Although our study was not sufficiently powered to draw conclusions on clinical efficacy and toxicities, the results are encouraging and should warrant further clinical trials evaluating the efficacy and adverse effects with a larger sample size. PMID- 17852948 TI - Whipple's disease in mentally retarded patients: report of two cases. AB - Of 21 patients diagnosed with Whipple's disease (WD) by polymerase chain reaction (PCR), 3 were mentally retarded. We describe 2 of these patients, both of whom had WD in the central nervous system. WD was confirmed with PCR on blood and, for 1 patient, also on cerebrospinal fluid (CSF). PMID- 17852949 TI - Arthritis and arthralgia three years after Sindbis virus infection: clinical follow-up of a cohort of 49 patients. AB - Sindbis virus (SINV) emerges as large human outbreaks in northern Europe every 7 years. Similar to many other alphaviruses, SINV is a mosquito-borne causative agent of a rash-arthritis. Previous reports suggest that in many alphavirus infections joint symptoms might persist for years. A prospective cohort of 49 patients was physically examined 3 y after verified acute SINV infection to reveal persistent joint symptoms. We carefully searched for a temporal association between the infection and current symptoms, and took into account other medical conditions. Sera were collected and analysed with enzyme immunoassays. Arthritis (swelling and tenderness on physical examination) was diagnosed in 4.1% (2/49) of the patients. Tenderness on palpation or in movement of a joint was found in 14.3% of the patients in the rheumatological examination, and an additional 10.2% complained of persisting arthralgia at the interview. Thus, 24.5% of the patients had joint manifestations attributable to the infection 3 y earlier. A positive IgM antibody response persisted in 3/49 of the patients; both patients with arthritis were in this group. As one-quarter of the patients were symptomatic 3 y after infection, it seems that persistent symptoms of SINV infection have considerable public health implications in areas with high seroprevalence. PMID- 17852950 TI - Clinical impact of infections caused by ESBL-producing E. coli and K. pneumoniae. AB - The outcome of infections occurring at different anatomic sites caused by ESBL producing E. coli or K. pneumoniae was retrospectively analysed for a 3-y period. 23 cases were compared to 46 controls with infections caused by third-generation cephalosporin-susceptible strains matched by age, severity of illness and duration of hospitalization before onset of infection. Only 27.8% of cases received appropriate empirical antimicrobial therapy compared with 79.6% of controls (OR(paired)=0.053, p=0.001). This did not result in higher costs of antibiotic therapy, a longer median post-infection hospital stay or higher mortality in cases of patients with urinary tract or wound infections. In cases of patients with respiratory tract and bloodstream infections (RTI/BSI), median costs of definitive antibiotic treatment were significantly higher than in controls (325 vs 58.9 Euros, p=0.002). Moreover, more case patients with RTI/BSI had a post-infection stay exceeding the 75th percentile of 15 d on ICU and of 18 d in hospital, respectively (50% vs 6.67%, p=0.034). There was no difference in in-hospital mortality between case and control patients with RTI/BSI (25% vs 20%, p=1.0). PMID- 17852951 TI - The platelet activating factor receptor is not required for exacerbation of bacterial pneumonia following influenza. AB - Pneumonia caused by Streptococcus pneumoniae is a significant cause of morbidity and mortality during influenza virus epidemics. We had previously advanced the hypothesis that interactions of pneumococcus with the receptor for platelet activating factor (PAFR) in the lung were facilitated by antecedent influenza virus infection and play a major role in the pathogenesis of bacterial superinfections. Although influenza enhanced the adherence of pneumococci to respiratory epithelial cells in vitro, chemical or antibody-mediated blockade of the PAFR did not affect adherence. In agreement with these data, mice lacking PAFR had similar bacterial loads within the lung compartment when compared to heterozygous littermates and were not protected from secondary pneumococcal pneumonia after influenza. Lack of support for this hypothesis and the observation of enhanced inflammation during secondary pneumococcal pneumonia in mice lacking PAFR may moderate enthusiasm for treatment strategies targeting the interaction of bacteria with PAFR. PMID- 17852952 TI - Concurrent PCP and TB pneumonia in HIV infected patients. AB - We aimed to assess the incidence and clinical characteristics of patients with HIV infection with concurrent Pneumocystis pneumonia (PCP) and tuberculosis (TB). We carried out a retrospective record review of HIV infected patients admitted with pulmonary TB and PCP during the same hospital admission at a large county hospital in Miami, from 1995 to 2004. 2651 patients with HIV infection and possible TB or PCP were identified. There were 99 cases of PCP (81 presumptive and 18 confirmed) and 35 were new cases of TB. There were 17 patients who had a new, concurrent diagnosis of pulmonary TB and PCP. Approximately half of these patients were unaware of their HIV infections and half of them had a negative AFB in sputum. Most were men and had a CD4 count less than 100 cells/mm(3). Chest X ray disclosed bilateral infiltrates in most of the cases. All but 2 survived the hospital admission. Thus, concurrent TB and PCP in HIV infected patients were not uncommon in this large county hospital in Miami, Florida in the studied period, but its diagnosis was challenging. PMID- 17852953 TI - Parasitological and immunological diagnosis of Strongyloides stercoralis in patients with gastrointestinal cancer. AB - This study examined the frequency of Strongyloides stercoralis infection in patients with gastrointestinal cancer through parasitological and immunological tests. A total of 77 patients were evaluated, 33 with gastrointestinal cancer and 44 controls with other types of cancers. All the patients were undergoing chemotherapy and 14 (18.2%) were receiving concomitant radiotherapy. For a parasitological diagnosis, we applied the Baermann and Lutz methods. The immunological diagnosis involved the indirect fluorescence antibody test (IFAT) and enzyme linked immunosorbent assay (ELISA) to detect IgG antibodies using Strongyloides ratti antigens. The frequency of positive S. stercoralis in gastrointestinal cancer diagnosed by parasitological methods was 3 cases (9.1%), by serology it was 8 cases (24.2%). In the control group 1 case (2.3%) of S. stercoralis was diagnosed by parasitological methods and 2 cases (4.5%) by immunological tests (p<0.05). Patients with gastrointestinal cancer had a 6.7 fold greater chance of testing positive for S. stercoralis infection. Our data highlight the importance of parasitological and immunological diagnosis for S. stercoralis in patients with gastrointestinal cancer living in endemic areas of strongyloidiasis, since they have a higher risk of becoming infected with S. stercoralis than patients with other types of cancer. PMID- 17852954 TI - Distinct genotypic distribution of cytomegalovirus (CMV) envelope glycoprotein B (gB) in a Cuban cohort of patients with different CMV diseases. AB - To investigate the association between human CMV glycoprotein B (gB) genotypes and CMV disease, we retrospectively analysed 73 biological samples from 56 Cuban patients with different CMV-related diseases using a multiplex nested PCR for detection of the reported 5 CMV gB genotypes. All 4 main genotypes 1 to 4 were found in the clinical samples while no genotype 5 was detected. Among the individuals analysed, genotype gB-2 was the most prevalent (38%) followed by gB-1 (30%) and mixed infections (16%) being mainly detected among immunosuppressed patients (7 out of 9), although there was no association between mixed infections and CMV rejection in transplant recipients. Genotype gB-4 was the least frequent (5 patients), which was almost exclusively detected in mixed infections (4 out of 5, p<0.0001). Genotype gB-1 was more frequently detected in AIDS patients (47%) although it was not statistically significant, while 68% of transplant patients showed mixed infections (p<0.05). This study represents the first report of human CMV gB genotypes in Cuban patients; however, the study is limited by the small number patients, thus making it difficult to draw firm conclusions about the distribution of CMV genotypes in Cuba. Nevertheless, this preliminary report has allowed us to identify that the main 4 CMV genotypes are present in the Cuban population, with genotypes 2 and 1 being the most frequent strains. PMID- 17852955 TI - An integrative review combined with a semantic review to explore the meaning of Swedish terms compatible with occupation, activity, doing and task. AB - The aims of this study were to explore the intended meaning of the terms "occupation", "activity", "doing", and "task" used in international occupational therapy literature and from this perspective explore which Swedish terms best capture these meanings. A literature review of occupational therapy-related journals was performed to gain a basic understanding of the term occupation and related terms. In addition, a semantic review was used: English and Swedish dictionaries were reviewed to explore the semantic meaning of the English terms "occupation", "activity", "doing", and "task", and the Swedish terms "aktivitet", "syssla/sysselsattning", "gorande", and "uppgift". A comparison was also performed by searching for parallels between the results of the literature review, the semantic definitions of the English and Swedish terms and the comprehensive meaning of the Swedish terms aktivitet and syssla/sysselsattning. An overarching idea of the concept of occupation was found in the literature review and for the purposes of this study we have identified this as Occupation for survival. From this overarching idea, three themes were identified: The feature of occupation, Impact of occupation and Occupation an occupational therapy concept. Each theme could be subdivided into sub-themes. The Swedish term aktivitet was found to have more power, strength, and spirit connected to the synonyms found in the semantic analysis than to those connected with the Swedish term syssla/sysselsattning. According to the findings in this study we found that the term "aktivitet" is the best comparable term in Swedish to the English term "occupation". PMID- 17852956 TI - Stability in women's experiences of hassles and uplifts: a five-year follow-up survey. AB - Hassles and uplifts, a concept used in measuring daily stress events, was applied to working mothers' everyday life. The aim was to explore the stability in working mothers' experiences in patterns of daily occupations, operationalized as hassles and uplifts, between the year 2000 (baseline) and the year 2005 (follow up). Further, the intention was to reveal possible differences in the number, origins, and ratings of hassles or uplifts between baseline and follow-up. The baseline study comprised 100 women, of whom 77 agreed to participate in the follow-up study. At baseline the questionnaire THU-5 was applied in the form of an interview, and at follow-up it was adapted to a self-response questionnaire sent home to the respondents. Stability was explored qualitatively by investigating the reported causes of hassles and uplifts, and quantitatively by comparing the numbers and ratings of the experiences at baseline and at follow up. The results indicate a certain amount of stability, although the cause of the experiences changes in line with changes in life stage. It was concluded that the methodology used (THU-5 and THU-3) was sensitive to these changes and could be applied in clinical settings, providing occupational therapists with a tool for detecting daily hassles that could be dealt with. Likewise, detected uplifts can be useful in the process of re-designing patterns of daily occupations affected by stress. PMID- 17852957 TI - Awareness through interaction in everyday occupations: experiences of people with Alzheimer's disease. AB - The aim of this study was to explore and describe the characteristics of awareness of the consequences of having Alzheimer's disease on everyday life occupations. Six community-dwelling participants with Alzheimer's disease were interviewed on repeated occasions about their lived experiences of everyday occupations. A phenomenological method was adopted for the analysis. The findings show that the participants discovered and explored the changes in how they performed everyday occupations in the context of their social relations and through immediate reflections on their forgetfulness. They attempted to handle the changes by adapting their behaviour. Awareness of the changes in their lives was evident in their reflections, as they tried to make sense of what was happening to them. This seemed to be related to an elusive perception of change in situations that they found impossible to influence. The participants reflected on the impact their condition had on other people near them. Their reflections also involved emotional reactions to the shortcomings they experienced. In conclusion, the findings show how these people with Alzheimer's disease were able to express awareness of the consequences of their illness through their reflections on their experiences of interaction with the occupations and the social environment. PMID- 17852958 TI - A randomized controlled trial of a health-promotion programme and its effect on ADL dependence and self-reported health problems for the elderly visually impaired. AB - BACKGROUND: Ageing with visual impairment is associated with a high degree of disability whereby age-related macular degeneration in particular causes dependence in activities of daily living (ADL) even at an early stage. AIMS: To compare an activity-based, health-promotion programme with an individual programme, targeting the elderly with age-related macular degeneration concerning the effect on the development of dependence in ADL, general health, and self reported health problems. METHODS: A randomized controlled study with a 28-month follow-up. A total of 229 persons were randomized to the study and 131 (57%) were followed up (individual intervention n=69, health-promotion programme n=62) at 28 month. RESULTS: The health-promotion group maintained their ADL level despite a significant decrease in visual acuity, while the individual intervention group increased its dependence in ADL. General health systematically dropped to a lower level in both groups, but participants from the health-promotion group reported fewer health problems. There were significantly fewer reports of tiredness and dizziness among the health-promotion participants. CONCLUSION: The health promotion programme seems to have slowed down the disablement process among elderly with decreased vision by enabling them to maintain their ADL level and by reducing self-reported health problems for at least 28 months following intervention. PMID- 17852959 TI - Activity-based assessment (BIA)--inter-rater reliability and staff experiences. AB - The BIA method, based on assessment of patients in activities, was developed to enable reliable assessment of clients' occupational functioning. The method evaluates the patient's ego functions and capacity for activity and participation. The aims of this study were to examine inter-rater reliability for the BIA method and to compare the experiences of staff working with the BIA with those of staff using standard assessment (SA). In SA, the patient's activity problems and capacities were assessed without using any structured protocol. Four staff members worked according to the BIA method and eight according to SA. The estimation of reliability was based on data from 14 patients who went through the BIA and were assessed by five staff members. These assessments resulted in all in about 400 statements, which were classified and compared for agreement between raters. In order to address the aim concerning staff experiences, a questionnaire was filled out anonymously by the staff. The inter-rater reliability of the nine ego functions varied from 0.76 to 1.00. The scale was deemed appropriate by the BIA staff and they had significantly higher median ratings on work satisfaction and appropriateness than the SA staff. In conclusion, the inter-rater reliability of the BIA was found to be good. The BIA method also seems to have a high degree of appropriateness, constituting a promising assessment tool when occupational functioning is addressed. PMID- 17852960 TI - Narrative slope as a predictor of work and other occupational participation. AB - This study aims to determine the utility of the narrative slope in predicting the vocational/productive outcomes of participants. For 65 participants living in supportive facilities for adults with HIV/AIDS in the United States, narrative slopes, based on the Occupational Performance History Interview II, were constructed and classified as progressive, stable, or regressive. Information regarding participants' productive activities was collected at discharge from intervention programming, and at 3-month intervals, up to 9 months. Data were analyzed to examine the relationship between narrative slope and engagement in employment and other productive activity post-intervention. Demographic variables were also analyzed. None of the demographic factors significantly correlated to outcomes. It was found that a more positive narrative slope was predictive of a higher likelihood of being employed or engaged in other productive activity. PMID- 17852961 TI - The Conceptions of Pain and Rehabilitation Questionnaire (CPRQ): development and test of face validity and stability over time. AB - The heterogeneity of diagnoses included in the concept of chronic pain, as well as differences in adaptation to the situation involving chronic illness, imply the need for a variety of rehabilitation forms. Despite evidence concerning the success of multidisciplinary behaviour-orientated rehabilitation programmes, not all participants experience the expected change. The aim of the present study was to develop and test the face validity and the stability over time of a Swedish self-administered questionnaire: the Conceptions of Pain and Rehabilitation Questionnaire (CPRQ) for persons with chronic pain. The questionnaire is to be used as a guiding tool in planning for rehabilitation. Its purpose is to distinguish between individuals with expectations of and motivation for active rehabilitation and those with expectations of more supportive forms of therapy. The face validity was mainly obtained by target-group discussions including persons with chronic pain and rehabilitation staff with experience in the rehabilitation of persons with chronic pain. The test-retest stability analysis was performed using a model for identifying occasional and systematic disagreement. The questionnaire in its final form showed face validity and reliability in terms of stability over time. Further steps in the development process will include laying down the guiding principles for the questionnaire, based on new focus-group discussions, and completing work on the manual by including information about the origin of the questionnaire and instructions for its administration. Thereafter, the next step in the development process will be a test of responsiveness, i.e. to examine the degree to which the questionnaire really serves its purpose. PMID- 17852962 TI - Using cultural-historical activity theory to study clinical reasoning in context. AB - The aim of this paper is to describe sources of conflict and congruence in critical areas of practice with caregivers of persons with dementia, using cultural-historical activity theory as an analytic framework. Findings are drawn from an ethnographic study that described the context of occupational therapists' (OTs') clinical reasoning in a funded, home-based environmental skill-building program designed to help caregivers manage the daily care of a family member with dementia. Data were gathered through observation of intervention sessions, debriefing sessions, semi-structured interviews with therapists, and review of intervention documentation. Primary sources of conflict and congruence within the identified practice context included conflicts between therapists and caregivers concerning which environmental strategies were best for addressing problems in caregiving and expectations regarding OT and caregiver roles. Areas of congruence included the fit between intervention protocols used to guide treatment and the approaches therapists developed to help caregivers modify care receivers' living environments. The study revealed the complexity of OT practice and demonstrated that practice contexts can be systematically analyzed using cultural-historical activity theory to determine key factors influencing clinical reasoning. The approach also presents an alternative perspective on clinical reasoning that more directly integrates clients/caregivers and therapists as co-constructors of OT intervention. PMID- 17852963 TI - Occupation as described by novice occupational therapy students in Sweden: the first step in a theory generative process grounded in empirical data. AB - A core assumption in occupational therapy is that occupation enhances health. This study is one of a series of planned studies carried out in Sweden, with the overall aim to develop a theory, based on empirical grounds, concerning the dimensions of occupation that may be useful in occupational therapy. The specific aim for this study is to examine the dimensions of occupation as generally understood among novice occupational therapy students. Grounded Theory was the chosen method. Data were collected among occupational therapy students. The students wrote down spontaneously what they considered to be included in activity. A preliminary core category "The what, why, and how of occupation" and five other categories emerged from the analysis: (1) The doing and context of occupation; (2) Motive for occupation; (3) Time and place for occupation; (4) Type of participation; and (5) Outcome of occupation. Relationships between the categories were established between the Motive for occupation and Outcome of occupation, which constitute a kind of prerequisite for occupation. The three remaining categories: The doing and context of occupation, Time and place for occupation, and Type of participation established a form for occupation. In conclusion, the study results illuminated the richness of the concept of occupation and support the core assumption in occupational therapy that occupation enhances health. PMID- 17852964 TI - Time use among individuals with persistent mental illness: identifying risk factors for imbalance in daily activities. AB - The aim of this study was to investigate associations between time use in daily activities and sociodemographic and clinical factors in order to identify individuals with persistent mental illness at risk of having an imbalance in daily activities, as reflected in their time use and daily rhythm. Participants (n = 103) were selected from a psychiatric outpatient unit using a randomized stratified selection procedure. The main findings indicated that time spent in daily activities increased with age, and that older individuals more often had a beneficial daily rhythm. Women and individuals living with children spent more time on self-care/self-maintenance than men and individuals living without children. Individuals with a diagnosis of psychosis spent less total time in daily activities than individuals with non-psychosis. In conclusion, general psychiatric symptoms, such as self-blame, anxiety, and difficulties in cooperating with others, explained most of the risk of spending little time in work/education as well as the risk of spending long periods asleep and having an adverse daily rhythm. A diagnosis of psychosis and high levels of general symptoms together explained most of the risk of having low total time use in activity. Factors such as age and living with children or not seemed to be important factors in relation to time use and daily rhythm. PMID- 17852965 TI - Effectiveness of occupational therapy with frail community living older adults. AB - This study examined the effectiveness of short-term, home-based occupational therapy guided by the Occupational Therapy Intervention Process Model for improving activities of daily living [ADL] with eight frail, older adults living in assistive living. A multi-method research approach was utilized to collect both quantitative and descriptive, qualitative data in the form of a retrospective examination of the participants' clinical records. The quantitative component was a within-subjects, repeated-measures analysis of participants' Assessment of Motor and Process Skills [AMPS] ADL motor and ADL process ability measures that revealed statistically significant improvement in ADL motor, but not ADL process abilities. The qualitative component was a content analysis of the clinical records. ADL baselines, goals, interventions and outcomes documented were analyzed. Improvement was noted in 77% of the written ADL goals. Results are discussed and recommendations were given for future research and documentation to improve the profession's ability to support evidence-based practice. PMID- 17852966 TI - Improving quality of ADL performance after rehabilitation among people with acquired brain injury. AB - The aim of this study was to evaluate whether people with brain injury show improvements in quality of performance of activities of daily living (ADL) after rehabilitation. A retrospective pre- and post-test design with no control group was used. Subjects received interdisciplinary rehabilitation consisting of restorative and compensatory strategies. Thirty-six adults with moderate to severe disability following acquired brain injury were evaluated using the Assessment of Motor and Process Skills (AMPS), an observational evaluation of the quality of ADL task performance. Paired t-tests revealed significant increase in ADL ability after intervention; effect sizes were medium. Improvements occurred across ages, within all diagnostic groups, and with no relation to time post injury. It was concluded that people with moderate to severe disability following acquired brain injury improved in ADL ability after participating in an intensive, interdisciplinary rehabilitation programme. Although lack of a control group prevented a conclusively conclusion that the changes were due to the intervention provided, the fact that the subjects had shown slow spontaneous recovery and minimal improvements before the study was implemented supports the likelihood that their gains were largely the result of the intervention. PMID- 17852967 TI - Validity and reliability of the instrument Performance and Satisfaction in Activities of Daily Living (PS-ADL) and its clinical applicability to adults with rheumatoid arthritis. AB - AIM: This study set out to evaluate the validity and reliability of the instrument Performance and Satisfaction of Activities of Daily Living (PS-ADL) in patients with rheumatoid arthritis (RA). The PS-ADL is a questionnaire including 39 actions divided into 12 activities measuring the degree of difficulty and satisfaction with activity performance. METHOD: Construct validity was examined by factor analysis. For convergent and discriminant validity evaluation, the Performance and the Satisfaction scales were correlated to the Health Assessment Questionnaire (HAQ), the Rheumatoid Arthritis Self-Conception (RASC), pain, fatigue, and mobility. Internal consistency was tested and repeated measurements were taken to establish the Percentage Agreement (PA) and correlation coefficients for test-retest reliability. RESULTS: The factor analysis revealed the PS-ADL scale to be unidimensional. Significant correlations were seen between the Performance and Satisfaction scales and the HAQ (r(s) 0.78, 0.67), and between the RASC and Satisfaction scale (r(s) 0.45). Cronbach's alpha level ranged from 0.41 to 0.92 for the Performance scale and 0.66 to 0.94 for the Satisfaction scale. The percentage agreement (PA) at action level ranged from 68% to 91% for the Performance scale and from 59% to 91% for the Satisfaction scale. CONCLUSION: The PS-ADL is a valid instrument with satisfactory reliability. It is easy to handle and can be recommended for use in RA patients. PMID- 17852968 TI - Examination of final-year medical students in general practice. AB - With general practice recognized as one of three major subjects in the Tromso medical school curriculum, a matching examination counterpart was needed. The aim was to develop and implement an examination in an authentic general practice setting for final-year medical students. In a general practice surgery, observed by two examiners and one fellow student, the student performs a consultation with a consenting patient who would otherwise have consulted his/her general practitioner (GP). An oral examination follows. It deals with the consultation process, the observed communication between "doctor" and patient, and with clinical problem-solving, taking today's patient as a starting point. The session is closed by discussion of a public-health-related question. Since 2004 the model has been evaluated through questionnaires to students, examiners, and patients, and through a series of review meetings among examiners and students. Examination in general practice using unselected, consenting patients mimics real life to a high degree. It constitutes one important element in a comprehensive assessment process. This is considered to be an acceptable and appropriate way of testing the students before graduation. PMID- 17852969 TI - Evaluation of current care effectiveness: a survey of hypertension guideline implementation in Finnish health centres. AB - OBJECTIVE: To assess the extent and style of implementation of the Hypertension Guideline (HT Guideline) in Finnish primary health centres, and to identify a scale of contrasting implementation styles in the health centres (with the two ends of the scale being referred to as information implementers or disseminators respectively). DESIGN: A cross-sectional study. Development of a questionnaire and criteria for assessing the extent and style of implementation of the HT Guideline. SETTING: Primary healthcare. SUBJECTS: All head physicians and senior nursing officers in Finnish health centres (n =290). MAIN OUTCOME MEASURES: The extent of adoption of the HT Guideline in health centres and the characteristics associated with the implementation style. RESULTS: Responses were received from 410 senior medical staff (246 senior nursing officers and 164 head physicians) representing altogether 264 health centres (91%) in Finland. The HT Guideline had been introduced into clinical practice in most health centres (89%). The style of implementation varied widely between health centres: at opposite ends of the implementation scale were 21 implementer health centres, which used multiple implementation channels, and 23 disseminator health centres, which used few or no implementation channels. The implementers had typically larger population bases and had organized services around the family doctor system, while the disseminators were smaller and had organized services according to a traditional model (appointments could be with any doctor in the surgery). CONCLUSION: The Finnish HT Guideline has become well known in most health centres since being introduced into clinical practice. However, the style of implementation varies markedly between health centres. PMID- 17852970 TI - Managing with maps? The development and institutionalization of a map-based health management information system in Madhya Pradesh, India. AB - AIMS: This paper presents the development of a map-based health management information system (mHMIS) in the central Indian province of Madhya Pradesh. Sample outputs and statistics from the system for one district are presented. The implementation dynamics and the preliminary performance of the system are discussed. METHODS: The development of the mHMIS was a collaborative effort between the provincial Department of Health, the medical university and the Danidasupported Madhya Pradesh Basic Health Services project. One of India's most socioeconomically backward provinces, Madhya Pradesh is spread over an area of 304,000 km(2), and has a population of 60.4 million distributed in its 55,392 villages and 394 towns. A primary survey of all healthcare providers (public and private) in the province was done to map these. Secondary data sources for sociodemographic information (census of India), vital statistics and health program indicators (health worker records) were used in developing the system. The process of mapping from obtaining hand-drawn maps of the villages from the commissioner, land records, to final digitizing is also described. CONCLUSIONS: Sample outputs and statistics for one district (Chindwara) from the system are presented. There were 20.35 trained doctors in rural areas and 72.78 in urban areas per 100,000 population. Preliminary experience after a year, advantages, constraints (both systemic limitations and weakness in the mHMIS) to optimal usage, and future prospects for use in this setting are discussed. PMID- 17852971 TI - The effect of patient origin and relevance of contact on patient and caregiver satisfaction in the emergency room. AB - AIMS: This study examined (1) whether patient and caregiver satisfaction in the emergency room (ER) varies according to patient origin, and (2) whether relevance of visit can explain any variation. METHODS: Data were obtained from a questionnaire survey of walk-in patients and their caregivers at four ERs in Copenhagen. The patient questionnaire was available in nine languages, and addressed patient satisfaction. The caregiver questionnaire addressed caregiver satisfaction and relevance of the patient contact in the ER. A total of 3,809 patients and 3,905 caregivers responded. The response rate among patients was 54%. Only data with both patient and caregiver responses and with patient country of birth were included in the analyses (n=3,426). The effect of patient origin was examined using bivariate, stratified analyses and tested for independence. RESULTS: Patients and caregivers had lower satisfaction rates when patients were of Middle Eastern compared with Danish origin. Satisfaction of both groups was associated with the relevance of the visit as assessed by the caregiver. Visits by patients of Middle Eastern origin were less often assessed as being relevant, but caregivers were less satisfied with visits by these patients even after controlling for relevance. Differences in patient satisfaction by patient origin were no longer significant when stratifying by relevance. CONCLUSIONS: Patient and caregiver satisfaction among patients of foreign origin can be improved by lowering the number of irrelevant visits among patients of foreign origin, e.g. by improving access to general practitioners. Training of caregivers in dealing with patients of different origins might reduce differences in caregiver satisfaction according to patient origin. PMID- 17852972 TI - Prestige and its significance for medical specialties and diseases. AB - AIMS: The aim of this paper is to review the literature concerning the existence of prestige hierarchies for medical specialities and diseases. Moreover, the implications of prestige for priority setting in healthcare systems are discussed. METHODS: The study is based on a review of the literature. Papers were obtained through the National Library of Medicine, PubMed. The search was conducted on 14 July 2005, and included articles from 1950 until that date. The medical subject headings "disease", "illness", and "medical specialities" were combined with the search word "prestige". A total of 183 papers were found. Only studies focusing on prestige hierarchies for medical specialities and diseases were included. The final search identified 20 articles, six of which specifically established hierarchies for medical specialities and diseases. RESULTS: The review documented prestige hierarchies for medical specialities and diseases. Explanatory characteristics behind the distribution of prestige were identified. It was demonstrated that active, specialized, biomedical, and high-technological types of medicine practised on organs in the upper part of the bodies of young or middle-aged people were accorded high levels of prestige. Medicine with the opposite characteristics had low levels of prestige. CONCLUSIONS: Medical specialities and diseases differ with regard to prestige. Characteristics related to specialties and diseases determine their prestige. The authors suggest that differences in prestige bear consequences for actual priority setting in healthcare systems, and contend that this should be further investigated. PMID- 17852973 TI - HIV testing in the Danish population: a national representative survey, 2000. AB - AIMS: To describe the accumulated prevalence of HIV testing in the Danish population until and including the year 2000. METHODS: The study was based on nationally representative data from the Danish Health Interview Survey 2000. Multiple logistic regression analysis investigated the association between HIV testing and background variables, such as gender, age, marital status, educational level, and sexual orientation. RESULTS: Overall 28.5% of the Danish population aged over 16 years have "ever been tested for HIV". More females (29.4%) than males (27.6%) were tested; 12.6% might not be aware of their blood being HIV tested when donating blood. More males (17.1%) than females (13.8%) had donated blood after 1985. Although males 30-39 years old were the most tested, males 50-59 years old had the highest odds of having donated blood after 1985. Concerning education, the less education one had, the less likely one was to have been HIV tested. Of men having sex with men, only 44% were "ever HIV tested". CONCLUSIONS: Positive association between extent of HIV testing and some sociodemographic factors was seen. Heterosexuals are HIV tested at lower rates than men having sex with men. Yet, stronger promotion of HIV testing among men having sex with men is recommended. Targeting prevention efforts towards other known risk groups is also recommended. PMID- 17852974 TI - Gender differences in experiencing negative encounters with healthcare: a study of long-term sickness absentees. AB - AIM: In most countries there are gender differences in sickness absence and in absentees' return to work (RTW). According to different theories sick-listed persons' experiences of encounters with healthcare professionals can influence self-esteem and RTW. The aim was to analyse gender differences in sickness absentees' experiences of negative encounters with healthcare professionals. METHODS: A questionnaire, comprising numerous questions on experiences of positive and negative encounters with professionals, was constructed and sent to 10,100 individuals who had been on sick leave for the last 6-8 months. The response rate was 58% (n = 5,802). RESULTS: Almost one-third (32%) of the female respondents and one-quarter of the male (24%), respectively, had experienced negative encounters. The most common of such experiences among both women and men were: that they were treated with indifference, with disrespect, that the professional did not take his/her time, did not listen, did not believe in, or doubted complaints. In regression analyses the women had higher significant crude odds ratios, ranging from 1.29 to 1.71, for agreeing to the separate statements on negative encounters. When adjusting for age, ethnicity, and level of education the gender differences were still significant for 14 of the 23 the statements. CONCLUSION: Women's high rate of sickness absence is considered a problem in most countries. The subjective experiences of women are an important factor to consider in efforts aiming at reducing the sick-leave rates. One important endeavour among professionals in healthcare could be to shift the focus towards a more empowering professional role. PMID- 17852975 TI - The effect of community nurses and health volunteers on child mortality: the Navrongo Community Health and Family Planning Project. AB - BACKGROUND: Despite effective treatments and preventive measures for the major causes of child illness and death in less wealthy nations, child mortality remains high in resource-poor settings due in part to ineffective health service delivery models. METHODS: The Navrongo Community Health and Family Planning Project is a longitudinal community trial of alternative organizational strategies for health service delivery in a rural, impoverished area of Ghana. In one area, nurses are placed in communities with doorstep visitation and service responsibilities. A second area includes training of a local health volunteer and community involvement in health delivery. A third area combines both strategies. Under-five mortality rates were calculated and Poisson regression was used to adjust for potential confounding characteristics. RESULTS: In areas with village based community nurse services, under-five child mortality fell by 14% during five years of program implementation compared with before the intervention, with reductions in infant (5%), early child (18%), and late child (39%) mortality. The volunteer intervention was associated with a 14% increase in mortality, primarily driven by a 135% increase in early child mortality. Areas with both nurses and volunteers saw an 8% increase, with small increases in all age groups. Mortality in a comparison area with standard Ministry of Health services fell by 4% during the same time period. CONCLUSIONS: These results suggest that convenient, accessible professional nursing care can reduce child mortality in impoverished African settings. However, they do not demonstrate a beneficial effect of community volunteers and suggest a possible negative impact on children's survival. PMID- 17852976 TI - Social predictors of non-attendance in an urban mammographic screening programme: a multilevel analysis. AB - OBJECTIVE: Rate of non-attendance following invitation for breast cancer screening is related to several socioeconomic conditions. To what extent this reflects differences with regard to individual and environmental circumstances, respectively, has received little attention. The purpose of this study was to investigate the effect of individual socioeconomic and area-level determinants on variations in non-attendance among geographic areas in an urban mammographic service screening programme. METHODS: The study population consisted of 32,119 women invited for mammographic screening in 1990-93, residing in 97 neighbourhoods in the city of Malmo in Sweden. The influence of the individual factors age, marital status, education, housing accommodation, household income, and area-level circumstances, e.g. rate of migration and rate of being gainfully employed, on the rate of non-attendance was assessed by multilevel analysis. RESULTS: Area rates of nonattendance ranged from 18% to 63%. Of the total variability in non-attendance, 4.3% was between neighbourhoods. This effect was significantly reduced when adjusting for the individual factors. The area-level factors, migration, and rate of being gainfully employed reduced and almost erased the neighbourhood variance in non-attendance. CONCLUSION: In addition to individual socioeconomic factors, area-level factors seem to be important determinants of neighbourhood rates of non-attendance in an urban mammographic screening programme. In a public health perspective neighbourhoods may be targeted in order to affect the problem of non-attendance in mammographic screening. PMID- 17852977 TI - Patients with burnout in relation to gender and a general population. AB - AIMS: The aims of this study were to describe gender differences in patients with burnout and compare these patients with a general population with respect to physical, psychosocial and work variables. METHODS: Data were collected from a total of 136 patients (96 women and 40 men, 41.6 +/- 7.4 years), diagnosed with stress-related disease and burnout at the Stress Clinic, University Hospital of Umea. Data on burnout, physical, psychosocial and work characteristics were compared with similar data from a geographical and age-matched population based survey, the 2004 Northern Sweden MONICA study. The survey sample included a total of 573 participants (283 women and 290 men, 40.7 +/- 8.5 years). RESULTS: Women with burnout reported a higher rate of impaired awakening, lower job control, greater proportion of unpaid work and worked to a greater extent "with people" compared to men. Men with burnout had a more restricted social network and reported working more overtime than women. Patients with burnout reported a higher rate of unemployment, a more restricted social network and higher work demands compared to a general population. Women with burnout reported less emotional support, a more sedentary work situation, high job strain and worked to a greater extent "with people" than women from the general population. CONCLUSIONS: There are some differences in working conditions and social network between women and men with burnout. Patients with burnout differ from a general population regarding individual and social factors as well as work-related factors. PMID- 17852978 TI - No difference in lifestyle changes by adding individual counselling to group based rehabilitation RCT among coronary heart disease patients. AB - AIMS: First, to examine whether autonomy-supportive and self-efficacy-enhancing individual lifestyle counselling was associated with improved maintenance of heart-protective diets and smoking cessation compared with group-based counselling. Second, to investigate to what extent reported motivation was associated with maintenance of dietary changes. METHODS: A randomized controlled trial and longitudinal study of predictor variables in a four-week heart rehabilitation setting with two years follow-up. A total of 176 (38 female) patients were included, mainly with coronary heart disease. The main outcome measures were dietary changes and smoking cessation. Motivational factors were tested for predictive power in the three dietary outcomes: daily intake of fruit and vegetables, a low saturated fat diet, and weekly intake of fish dinners. RESULTS: No clinically significant difference in improvement of dietary maintenance was found between the two groups. The between-group difference in smoking status change was statistically insignificant (p = 0.12). Both groups showed an improvement in their dietary measures. Self-efficacy predicted an increased frequency of eating fish dinners (p = 0.001) and more daily units of fruit and vegetables (p < 0.001). Autonomous motivation had a marginal association with increased intake of fruits and vegetables (p = 0.08) and was significantly associated with a lower saturated fat diet (p = 0.001). CONCLUSIONS: Among this highly motivated group of rehabilitation patients, no effect was found of adding autonomy-supportive, individual counselling to group based interventions. Based on longitudinal documentation, this cardiac rehabilitation programme improves long-term maintenance of dietary changes, and this maintenance is related to autonomous motivation and self-efficacy. PMID- 17852979 TI - Migration and coronary heart disease: A study of Finnish twins living in Sweden and their co-twins residing in Finland. AB - BACKGROUND: Finland and Sweden are neighbouring countries with a substantially higher incidence and mortality from coronary heart disease (CHD) in Finland. Migration from Finland to Sweden has resulted in a population of about 187,000 Finnish immigrants, with a higher risk of CHD than Swedes. The aim of the present study was to analyse the prevalence of CHD in migrants to Sweden compared with co twins remaining in Finland. METHODS: The study population consisted of twin pairs of the Finnish Twin Cohort Study where at least one twin had lived one year or more in Sweden, including 1,534 subjects and 251 complete twin pairs discordant regarding residency in Sweden. Emigrant twins were compared with nonmigrant co twins regarding prevalence of CHD in 1998. CHD prevalence was assessed by self reported questionnaires validated using information from a clinical examination. RESULTS: Self-reported CHD showed a good correspondence with clinical diagnosis. Differences in social and behavioural risk factors for CHD among men were small but emigrants were more physically active than non-migrants. Female emigrants had less overweight and better education, but were more often working class than non migrants. Intra-pair comparisons restricted to migration discordant pairs showed a tendency towards a reduced prevalence of CHD in the migrant co-twins (0.6; 0.3 1.4). In analyses of all subjects disregarding pair status, emigrants showed a reduced prevalence of CHD compared with subjects always living in Finland (0.6; 0.4-0.9). CONCLUSION: Emigration from Finland to Sweden may be associated with a reduced prevalence of CHD. The causes are most likely multifactorial and may involve changes in dietary habits, physical activity, psychosocial factors, and inflammation. PMID- 17852980 TI - Register-based follow-up of social benefits and other transfer payments: accuracy and degree of completeness in a Danish interdepartmental administrative database compared with a population-based survey. AB - BACKGROUND: Social consequences of disease may be subject to register based follow-up. A Danish database, DREAM, allows weekly follow-up of any public transfer payment. This study aimed to evaluate the feasibility of the register for use in public health research. MATERIAL AND METHODS: The DREAM database includes information on all public transfer payments administered by Danish ministries, municipalities, and Statistics Denmark for all Danish citizens on a weekly basis since 1991. The DREAM database was compared with self-reported information on sources of income in a population survey from 2001 with about 5000 participants. RESULTS: According to DREAM, 80.2% of respondents had received some kind of transfer income since 1991. For the week they filled in the questionnaire, 9.0% had a record of labour-market-related benefit (unemployment benefit, social assistance, wage subsidy), 6.4% a health-related benefit (sickness benefit, vocational rehabilitation allowance, salary from subsidized jobs for persons with limited work capacity, anticipatory pension), 10.1% a voluntary retirement pension, while 74.4% had no record of transfer payment for that week. The predictive value of DREAM was 74.8% for health-related transfer payment and 98.2% for self-support. Among persons with a record of sickness benefit, 52.4% reported no transfer payment. CONCLUSION: The DREAM database is feasible for follow-up of social and economic consequences of disease. Respondents may be unaware of payments transferred by the public authorities to the employer, and in such cases DREAM may be the best source of information. The database is useful for public health research, but may also be useful for socioeconomic analyses of selection bias and dropout from other studies. PMID- 17852981 TI - Preschool children's sickness absenteeism from Norwegian regular and outdoor day care centres: a comparative study. AB - AIMS: To examine whether there are any differences in sickness absenteeism between children in outdoor day care centres and regular day care centres and also to investigate whether other variables predict sickness absenteeism. METHODS: Data on sickness absence during a 4-week period together with several explanatory variables of 531 children in 32 regular and 37 outdoor day care centres were collected and included in the analysis. The data were analysed by generalized linear modelling. RESULTS: The overall frequency of sickness absence was 5.1%. There was no general significant difference between sickness absenteeism in regular and outdoor day care centres. Of the other possible explanatory variables only two were found to contribute significantly: age, with a negative relationship, and the interaction effect of a child with a chronic disease or disability going to an outdoor day care centre, with a positive relationship. CONCLUSIONS: The present study indicates that sickness absenteeism of a child without a chronic disease or disability is not affected by whether the child attends a regular or an outdoor day care centre. There seem to be no health benefits for children with chronic diseases or disabilities to attend outdoor day care centres--there is in fact evidence that sickness absence for those children is higher in outdoor centres. PMID- 17852982 TI - Patients retrieving additional information via the Internet: a trend analysis in a Swedish population, 2000-05. AB - AIMS: To examine the trends over five years for patients' seeking online additional health information about their disease/health problem to what the doctor has been giving, and investigate any differences in information-seeking behaviour according to age, gender, self-perceived health status, living area, and type of medical encounter. METHODS: Data from three independent surveys conducted in 2000, 2002, and 2005 of a population with a recent experience of outpatient care[n]typesetter: please remove blue shading here and elsewhere[/n], including 24,800 respondents aged between 20 and 95, were analysed in a trend analysis and a logistic regression regarding background factors that may influence the seeking behaviour. RESULTS: During the study period, there was a significant increase in Internet use in most age groups. The total use among men 20-95 years old increased from 7% in 2000 to 18% in 2005 and from 9% to 25% for women respectively. The predictors for using the Internet as a source of information were: age, gender, self-perceived health status, living area, and the type of medical encounter (first or repeated). In 2005, women aged 20-49 used the Internet as a source to a significantly greater extent than men, even when all background factors were controlled for (OR 1.46 and CI 1.21-1.77). CONCLUSIONS: Swedish patients, especially the young and middle-aged, are to a substantial degree using the Internet to gather additional information on their disease. The benefits of this increase include more informed patients; however, there are inherent quality issues that require strategies for ensuring public access to high-quality health information online. PMID- 17852983 TI - Social capital, institutional (vertical) trust and smoking: a study of daily smoking and smoking cessation among ever smokers. AB - OBJECTIVES: The associations between vertical (institutional) trust in the healthcare system and the mass media (newspapers and television), and daily smoking and smoking cessation were investigated. METHODS: The 2004 public-health survey in Scania is a cross-sectional study. A total of 27,757 persons aged 18-80 years answered a postal questionnaire, which represents 59% of the random sample. A logistic regression model was used to investigate the associations between institutional trust in the healthcare system and the mass media, and daily smoking and smoking cessation. A multivariate analysis was performed to investigate the importance of possible confounders (age, country of origin, education, economic stress, generalized trust in other people) on the differences in daily smoking and smoking cessation according to trust in the healthcare system and the mass media. RESULTS: 14.9% of the men and 18.1% of the women were daily smokers. Middle-aged respondents were daily smokers to a significantly higher extent than the young. Respondents with low trust in the healthcare system had significantly higher odds ratios of daily smoking, 1.88 (95% CI 1.38-2.57) among men and 2.05 (95% CI 1.51-2.78) among women, while respondents with low trust in the mass media had no significant odds ratios of daily smoking, 1.01 (0.67-1.52) among men and 1.55 (0.97-2.47) among women, after multiple adjustments. CONCLUSIONS: Institutional (vertical) trust in the healthcare system but not the mass media was significantly associated with lower odds of daily smoking and higher odds of having quit smoking if ever smoker. The healthcare system seems to be a potent arena for tobacco prevention. PMID- 17852984 TI - Prediction of perinatal mortality at an early stage of pregnancy. AB - AIM: To define the probability of foetal and neonatal death (PFND) in Lithuania by means of the Medical Birth registry. METHODS: The Medical Birth registry for the year 2002 (29,619 pregnancies resulting in delivery) was used, covering social, environmental, health behaviour factors, obstetric history, health status of pregnant women, and delivery. RESULTS: A statistically significant model has been obtained in which 12 out of 45 analysed factors were significant for the risk of perinatal mortality (PM). In the case of previous neonatal pathology, e.g. damage to CNS, the risk of PM (OR 5.2; 95% CI = 2.1-13.3) was similar to the reported manual work or harmful working conditions during pregnancy (OR 4.8; 95% CI = 1.9-12.1 and OR 4.5; 95% CI = 1.3-15.2, respectively). The influence of father's alcohol abuse (OR 2.6; 95% CI = 1.4-4.7) was comparable to that of the stillborns or premature deliveries. The combination of several factors increased PFND significantly: maternal smoking during pregnancy and paternal smoking and alcohol abuse raised PFND to 0.03 (OR 6.8), mother's hard manual work in combination with harmful conditions during pregnancy increased OR more than 10 times (PFND 0.32) as compared with the situation when only one of those factors was present. CONCLUSIONS: The influence of social, environmental, and behavioural factors on the risk of PM was comparable to that of some of the complications during a previous pregnancy. The combination of risk factors significantly increased PFND. Using modelling, the individual prognosis may be presented to every pregnant woman at an early stage of pregnancy to potentially decrease the impact of unfavourable risk factors on PM. PMID- 17852985 TI - Housing conditions in childhood and cause-specific adult mortality: the effect of sanitary conditions and economic deprivation on 55,761 men in Oslo. AB - AIMS: To examine indices of two plausible pathways linking housing conditions in childhood and adult cause-specific mortality: sanitary conditions and economic deprivation. To investigate if the effects of these are explained by education. METHODS: Linked register study (housing information from the 1960 Census, the educational register in 1990 and the death register 1990-998). A Sanitary Conditions Index (SCI) and an Economic Deprivation Index (EDI) were constructed from the housing conditions variables. PARTICIPANTS: All men aged 30-54 years (n = 55,761) who were residents in Oslo on 1 January 1990 with complete information on housing conditions (80%). RESULTS: Both SCI and EDI were related to all-cause mortality independently of each other. Education explained to a large extent these effects. In a sub-sample, 24% of the effects could be explained by parental education and 31% by own education. The effects found for causes of death failed to give a heterogeneous pattern between the two indices. In the fully adjusted model psychiatric causes of death appeared to be more related to EDI than SCI. CONCLUSIONS: The two indices of childhood social circumstances, sanitary conditions and economic deprivation, appeared to be independently associated with all-cause mortality. The effect of both could to a large extent be explained by parental and own education. PMID- 17852986 TI - Prevalence of hearing loss among 18-year-old Swedish men during the period 1971 1995. AB - AIMS: To study the hearing of 18-year-old men by using screening audiograms obtained at military conscription. METHODS: The study group comprised 301,873 Swedish men belonging to six age cohorts born from 1953 to 1977 who had been screened at age 18 years from 1971 to 1995. The prevalence of mild to moderate hearing loss was investigated. RESULTS: Of the entire study group, 13.1% had elevation of one or more pure tone thresholds. In most cases, 11.9%, the elevation was situated in the high-frequency region. High-frequency hearing loss was more common in the left ear (7.5%) than in the right ear (6.2%). The prevalence of hearing loss decreased during the period 1971 to 1981 from 15.7% to 8.3%. During the last part of the study period, 1986 to 1995, the prevalence increased from 9.8% to 16.3%. The increase included mild to moderate degrees of hearing loss with thresholds below 35 dB HL. The prevalence of threshold elevations was highest in sparsely populated areas of Sweden and lowest in large, metropolitan areas of Sweden from 1971 to 1986. During the last part of the study period the geographical differences decreased or disappeared. CONCLUSIONS: The total prevalence of hearing loss was in accordance with other reports. The frequency 6 kHz was most affected by threshold elevations. The prevalence of hearing loss decreased in the first part of the study period, and increased at the end of the study period. Hearing loss was most commonly seen in rural areas. PMID- 17852987 TI - Urban-rural differences in BMI, overweight and obesity in Norway (1990 and 2001). AB - AIM: The aim of this study was to examine body mass index and the prevalence of overweight and obesity in 1990 and 2001 in Oslo and Lofoten, Norway. METHODS: A randomly selected study population of 1,924 individuals (OsLof) underwent a structured personal interview in 1990. In 2001, 1629 individuals underwent the same interview. These samples were analysed as two cross-sectional datasets. RESULTS: Overall mean BMI in 1990 was 24.7 for men and 22.9 for women, increasing significantly in 2001 to 26.1 and 24.6, respectively. In 1990, 37% of men and 20% of women were overweight, while 5% of men and 4% of women were obese. The corresponding figures for 2001 were 48% and 27% for overweight, and 12% and 11% for obesity, respectively. DISCUSSION: The greatest increases in average BMI occurred for the youngest (18-34 years) for both genders and geographic regions. In 1990, urban-rural differences existed for mean BMI and proportion overweight for both genders, although geographic differences persisted only for women 10 years later. PMID- 17852988 TI - Impact of selected risk factors on quality-adjusted life expectancy in Denmark. AB - AIMS: The construct quality-adjusted life years (QALYs) combines mortality and overall health status and can be used to quantify the impact of risk factors on population health. The purpose of the study was to estimate the impact of tobacco smoking, high alcohol consumption, physical inactivity, and overweight on QALYs. METHODS: Life tables for each level of exposure to the risk factor were constructed mainly on the basis of the Danish National Cohort Study. QALYs were estimated for exposed and unexposed by Sullivan's method, by combining life tables, EQ-5D self-classified health status from the Danish Health Survey 2000, and Danish EQ-5D values. RESULTS: The quality-adjusted life expectancy of 25-year olds was 10-11 QALYs shorter for heavy smokers than for those who never smoke. The difference in life expectancy was 9-10 years. Men and women with high alcohol consumption could expect to lose about 5 and 3 QALYs, respectively. Sedentary persons could expect to have about 7 fewer QALYs than physically active persons. Obesity shortened QALYs by almost 3 for men and 6 for women. CONCLUSIONS: Smoking, high alcohol consumption, physical inactivity, and obesity strongly reduce life expectancy and health-related quality of life. These results could be used by health policy-makers to evaluate the potential gains in public health due to interventions against these risk factors, when the prevalence of exposure to the risk factor is available. PMID- 17852989 TI - The NORPEQ patient experiences questionnaire: data quality, internal consistency and validity following a Norwegian inpatient survey. AB - AIMS: This article describes the development of a questionnaire designed for comparisons of patient experiences of hospital care within the Nordic countries. The results of testing for data quality, reliability, and validity are presented following a Norwegian survey. METHODS: Following a literature review and consultation within an expert group six items were developed measuring patient experiences together with two items assessing global satisfaction and perception of incorrect treatment. The questions were included in a questionnaire that was mailed to 500 patients randomly selected from patients receiving inpatient treatment at a large university hospital in Norway. Principal component analysis was used to assess dimensionality. Reliability was assessed by the internal consistency and test-retest methods. Construct validity was assessed by the scale's correlation with variables known to be related to patient experiences. RESULTS: A total of 244 (48.8%) patients responded. Levels of missing data ranged from 0.4% to 2.5%. The six items in the questionnaire that measured important aspects of patient experiences with the services contributed to a single scale with item-total correlations in the range 0.59-0.71 and a Cronbach's alpha of 0.85. The test-retest intraclass correlation was 0.88. CONCLUSIONS: The NORPEQ is a brief measure of patient experiences that covers important aspects of the healthcare encounter. It shows good evidence of reliability and validity and is relatively easy to apply alongside existing national surveys. PMID- 17852990 TI - Ethics of prevention: an interactive computer-tailored program. AB - AIM: This article describes the contents of an interactive computer-tailored program. The program is based on previous studies of the practice of care for persons with Prader-Willi syndrome. This genetic condition is associated with a constant overeating behaviour with the risk of obesity. The aim of the program is to start a process of awareness, reflection, and discussion by caregivers who are confronted with the moral dilemma of respect for autonomy versus restricting overeating behaviour. The program focuses on values (such as health and well being) that are relevant to caregivers in daily practice. Furthermore, the focus is on various ways of interaction with the client. Caregivers were expected to focus mainly on health, and on both paternalistic and interpretive/deliberative forms of interaction. METHODS: Sixteen professionals and 12 parents pilot-tested the program contents. With a pre-test, responses on one central case were collected for tailored feedback; with a post-test, the effects of the program were measured. RESULTS: Significant correlations were found between the values of autonomy and consultation and between autonomy and well-being. In contrast to our expectations respondents valued all categories (autonomy, consultation, health, well-being, and liveability for others) as equally important in the pre-test. No significant changes in scores were found between pre- and post-test. The open answers and remarks of participants support the program contents. CONCLUSIONS: Participants' responses support previous research findings, advocating a concept of autonomy in terms of positive freedom, through support by others. The promotion of the client's self-understanding and self-development is central in this concept. PMID- 17852992 TI - Types of cultural capital and self-rated health among disadvantaged women in outer Beirut, Lebanon. AB - AIMS: This study extends research on the social determinants of health by exploring the association between a new, potentially very significant dimension, cultural capital by type, and self-rated health among low-income women living in outer Beirut, Lebanon. METHODS: Self-rated general health was assessed using household data from a cross-sectional survey of 1869 women, conducted in 2003. Three types of cultural capital were included: watching cultural TV programs, producing art (e.g. drawing, theatre performance), and consuming art or literature (e.g. attending exhibitions, reading literary books). Associations between self-rated health status and types of cultural capital were assessed using odds ratios from binary logistic regression models. RESULTS: With the exception of art production, lack of cultural capital increased the odds of self perceived poor health status adjusting for sociodemographics and other risk factors. The adjusted odds ratios were 1.86 (95% CI 1.07-3.22) for not watching cultural TV programs and 1.52 (95% CI 1.12-2.06) for not consuming art. As expected, health-risk factors, age, social support, and community of residence were also associated with health status. CONCLUSIONS: Two types of cultural capital were strong predictors of self-perceived health status among women living in poor urban communities, regardless of social capital, income, and other relevant risk factors. PMID- 17852993 TI - Hospital contacts for chronic diseases among danish seafarers and fishermen: a population-based cohort study. AB - OBJECTIVES: Seafarers' and fishermen's working conditions may impact on their lifestyle and health. Standardized hospital contact ratios (SHCRs) were compared in two time periods and the relative risks of hospital contact as a function of employment time were estimated. METHODS: Cohorts of all Danish seafarers (officers and non-officers) registered by the Danish Maritime Authority (DMA) 1989-98 and fishermen retrieved from a pension registry 1989-98 were linked to the nationwide Occupational Hospitalization Registry (OHR) and followed up for incident diseases in two five-year time periods, from 1 January 1994 and 1 January 1999, respectively, using rates specific for age and calendar time for the entire Danish workforce as a reference. RESULTS: The SHCRs for lung and cardiovascular diseases were high for non-officers. Among male officers, the SHCR for diabetes was high in the 1999 cohort and the SHCR for chronic heart diseases was statistically significantly higher in the 1999 than in the 1994 cohort. For both time periods high SHCR values were found for bronchitis, emphysema, cancer of the lung, alcohol-related liver diseases, and diabetes among male non officers, and lung cancer among male officers. Among female non-officers, a high SHCR for skin melanomas was seen. Among fishermen high SHCRs for bronchitis, emphysema, lung cancer, and Raynaud's syndrome were found in both cohorts. No duration-response pattern was observed in any of the analyses, which may reflect health- and lifestyle-related selection into the trades or a healthy worker effect. CONCLUSIONS: Danish seafarers, especially short-term employees, had an elevated risk of hospitalization for lifestyle-related diseases. PMID- 17852994 TI - Social capital and inequality in health between single and couple parents in Sweden. AB - AIMS: To study whether social capital is associated with health among parents and if so, whether existing inequalities in health between single and couple parents could be better understood by introducing social capital as a possible mechanism for how health is distributed. MATERIAL AND METHODS: At total of 2,500 parents with children in the age range of 4-16 years were randomized from existing national registers and asked to participate in a nationally distributed postal questionnaire; 1,589 parents participated (277 single and 1,312 couple), giving a response rate of 64%. The questionnaire contained questions regarding sociodemographic and socioeconomic characteristics, self-rated health, emotional and instrumental social support, civic and social participation, and trust. Social capital was measured by different levels of civic and social participation and trust. A multivariate analysis was used in order to find possible associations between social capital and health, when adjusted for social support, sociodemographic and socioeconomic characteristics. RESULTS: A low level of social capital (both social participation and trust), when adjusted for social support, socioeconomic and sociodemographic variables, was clearly and positively associated with less than good self-rated health. Social capital was unevenly distributed between single and couple mothers. CONCLUSIONS: Social capital is positively associated with self-rated health, at an individual level. The uneven distribution of social capital between single and couple mothers may be of some importance when trying to further understand and possibly alter the inequality in health that exists between single and couple parents. PMID- 17852995 TI - Violence against women in intimate relationships: explanations and suggestions for interventions as perceived by healthcare workers, local leaders, and trusted community members in a northern district of Vietnam. AB - AIM: This study explored professionals' and trusted community inhabitants' explanations of the violence between intimate partners and their suggestions for preventive activities. It was performed in a rural district in northern Vietnam. METHODS: A total of 20 men and 20 women were strategically selected for focus group discussions and the analyses followed the procedure for qualitative thematic content analysis. RESULTS: It was pointed out that violence against women was not discussed openly in the community and women subjected to violence kept silent and avoided seeking help in order not to reveal what was happening in the family. The informants perceived the violence as an interplay between individual and family-related factors and sociocultural norms and practices where Confucian ideology exerted a strong influence. When it came to prevention, there was a strong belief in educating the people and in enforcing policy and law. CONCLUSIONS: As described by the informants, traditional attitudes to gender roles and women's power disadvantage are found to be behind most of the explanations for intimate partner violence. Collaboration between sectors at local level, between the health sector and other bodies, and with community leaders as spokesmen would help to improve openness and reduce society's tolerance of violence against women. The mass media also have an important role to play. PMID- 17852996 TI - Is moist snuff use associated with excess risk of IHD or stroke? A longitudinal follow-up of snuff users in Sweden. AB - BACKGROUND: The potential risks of Swedish moist snuff (snus) are debated and studies have shown diverging results. AIMS: The aim of this study is to investigate whether there is any excess risk of ischaemic heart disease (IHD) and stroke from snuff use. METHODS: The Swedish Survey of Living Conditions from 1988 89 was record-linked to the Swedish Cause of Death Register and the Swedish Hospital Discharge Register to investigate excess mortality and hospitalization from IHD and stroke. A Poisson regression model was used and incidence rate ratios (IRRs) for snuff and smoking were calculated controlling for age, physical activity, self-reported health, number of longstanding illnesses, residential area, and socioeconomic position. RESULTS: Among snuff users there were no excess risks of mortality or hospitalization from IHD (IRR 0.8; 0.5-1.2,) or stroke (IRR 1.1; 0.7-1.8), but, as expected, clear excess risks were found for smokers (IRR 1.7; 1.4-2.1 for IHD, and IRR 1.4; 1.0-1.9 for stroke). CONCLUSIONS: This study has not shown any excess risk among users of snuff for IHD or stroke. If there is a risk associated with snuff it is evidently much lower than those associated with smoking. PMID- 17852997 TI - Personal health documents in school health education: a feasibility study. AB - AIMS: To examine the feasibility of a school intervention using a personal health document adapted for adolescents. METHODS: The health document was developed in close cooperation with groups of adolescents and tested among seventh-grade students at two junior high schools (n = 339). The document was presented to the students by their regular teachers. For evaluation, an adolescent questionnaire was used at baseline and after one year. RESULTS: After one year, 87% of adolescents reported having written in the health document, and 77% reported having had classes with discussions on subjects in the document. The health document was perceived as useful by 35% of the adolescents. Factors significantly related to personal usefulness were being born outside Sweden, experiencing fair treatment by teachers, being a nonsmoker, and having a positive school experience. CONCLUSIONS: Implementation of a personal health document in junior high-school health education was feasible and well accepted. PMID- 17852998 TI - Critiques of the risk concept--valid or not? AB - The increasing use of the risk concept in healthcare has caused concern among medical doctors, especially general practitioners (GPs). Critics have claimed that risk identification and intervention create unfounded anxiety, that the concept of risk is not useful at the individual patient level, that patients' risk concept is different from an epidemiological one, that resources are better spent elsewhere, or that commercial interests take advantage of risk information to promote sales. In this paper the authors discuss the concept of risk and address the critique. There is evidence that commercial interests promote risk interventions, that patients may misunderstand risk information, and that risk information can cause unnecessary anxiety. The authors have found no empirical data on the amount of time primary healthcare providers spend on risk interventions, and have not identified any valid arguments that risk information is not useful for the individual patient. Decision-making under uncertainty is a core element of medical practice, and GPs need to be suitably trained to inform patients such that they make good decisions when they are faced with uncertainty. The concept of risk is therefore useful for GPs, and in fact a key issue. It is concluded that risk critique should be based on sound theory and empirical data. Critics may do well in making clear distinctions between facts and value judgements. PMID- 17852999 TI - Differences in child injury hospitalizations in Sweden: the use of time-trend analysis to compare various community injury-prevention approaches. AB - AIM: Sweden's child injury fatality rates are among the lowest in the world. The country has engaged in a number of community injury-prevention programmes. The purpose of this study was to compare child injury hospitalization rates from the Skaraborg District with the rest of Sweden. Our study hypothesis was that municipalities that offered comprehensive child injury-prevention programmes would see significant decreases in their child injury hospitalization rates, compared with other areas. METHODS: The study areas comprised three groups, consisting of municipalities in Skaraborg that had adapted the Safe Communities approach to injury prevention programmes, other municipalities in the District, and the rest of Sweden. The aim of the analysis was twofold: (1) to fit time trends for children's injuries in various areas in an integrated manner; and (2) to compare time trends across locations between community safety-promotion programmes as well as with the control areas. Panel data models and parametric splines were used. RESULTS: There were differences between incidence rates in the study areas and with regard to gender. There was a steep decrease in injury rates in one of the Safe Communities study areas for both genders. CONCLUSIONS: The methods applied in this analysis reveal more detailed and sophisticated time trends than the usual simple linear regression approach. The model provided a clearer view of the interactions of gender, area, and time as they impacted on children's injuries, and allowed for better insight into the impact of safety programmes. PMID- 17853000 TI - Is GATS a concern for the Swedish healthcare system? PMID- 17853001 TI - Gender and images of heart disease in Scandinavian drug advertising. AB - AIMS: This study examines the construction of the "heart disease candidate" in advertisements for cardiovascular drugs in Scandinavian medical journals. METHODS: All advertisements for cardiovascular drugs (n = 603) in Scandinavian medical journals (Denmark, Finland, Norway, and Sweden) in 2005 were collected. Only advertisements that portray users (n = 289, 48% of the advertisements) were analyzed. RESULTS: The results show that coronary candidacy is constructed as a male condition in half of the advertisements for cardiovascular drugs. The advertisements suggest a gendering of heart disease: men are the major victims of heart failure and cardiac insufficiency, and women are in need of cholesterol lowering drugs. The cardiovascular drug advertisements portray a restoration of men's hyperactive agency, valorized by means of sporty images, by drawing on masculinity as a fixed trait and behavior. Hypercholesterolemia as a woman's disease reproduces the tyranny of slimness for women: Only women's stoutness is medicalized, and there are no pictures of heavy men. CONCLUSIONS: The findings point to the public health implications of gendered images of coronary candidacy in medical advertising. PMID- 17853002 TI - Self-rated general health among 40-year-old Danes and its association with all cause mortality at 10-, 20-, and 29 years' follow-up. AB - AIMS: Self-rated general health (SRH) predicts future mortality. We examined all cause mortality at 10, 20, and 29 years' follow-up and its association with SRH measured at the age of 40 years in a cohort of 1,198 healthy Danes born in 1936 and who were residents in suburban Copenhagen. METHODS: The association between SRH (dichotomized into good versus poor) and all-cause mortality was estimated in standard time-homogenous Cox regression models adjusting for covariates related to mortality, and in time-heterogeneous Cox regression models without covariate adjustment, where time-heterogeneity features as a separate risk assessment for each of the three follow-up periods defined by the follow-up examinations. RESULTS: At the age of 40 years, 153 (14.6%) of 1,045 participants reported poor and 85.4% good SRH. Dead participants totalled 36 at the 10-year, 96 at the 20 year, and 207 at the 29-year follow-up. For poor SRH, mortality hazard ratios (multivariate analysis) were persistently significant, but slowly declining with follow-up time. The time-heterogeneous models explain this feature: increased mortality risk was significant only in the first decade after assessment: 2.30 (95% CI 1.11-4.78) vs. 0.91 (95% CI 0.36-2.31) and 0.73 (95% CI 0.34-1.55). CONCLUSIONS: The association between poor SRH and mortality emphasizes the importance of health personnel taking account of people's health rating, particularly when a recent assessment has been made. SRH is related to death, even when controlling for known covariates, but it is not a long-term effect. PMID- 17853004 TI - The Internet and prostate cancer patients: searching for and finding information. AB - OBJECTIVE: To define the characteristics of prostate cancer patients who use the Internet. MATERIAL AND METHODS: In October 2002, 511 prostate cancer patients from Stockholm-Gotland County completed a postal questionnaire consisting of 146 questions regarding use of the Internet, demographic factors, level of information about the disease and its treatment, quality of life and trade-off possibilities. RESULTS: The response rate was 86.5% (n=511) and the mean age of the respondents was 71 years. A total of 210 men (41.1%) had access to the Internet. Eighty-two men (16.4%) had looked for information on prostate cancer, either by themselves or with the aid of others. Among men aged 50-60 years, 39% were Internet users, compared to 8% among men aged 75-80 years; the figures for university graduates versus those who had only attended elementary school were 33% and 3%, respectively. Fifty of the 82 men (61%) who searched for information regarded themselves as being satisfactorily informed by online information. CONCLUSIONS: Of the men in this cohort, 16% searched the Internet for information regarding their prostate cancer. Young and well-educated men utilized the Internet more frequently than others, but they did not find information more often than older and less well-educated men. It is possible that the Internet promotes social inequality in obtaining healthcare in favor of well-educated, highly paid individuals. PMID- 17853003 TI - The role of nitric oxide in osteoarthritis. AB - Elevated levels of markers of nitric oxide (NO) production are found in osteoarthritic joints suggesting that NO is involved in the pathogenesis of osteoarthritis (OA). In OA, NO mediates many of the destructive effects of interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) in the cartilage, and inhibitors of NO synthesis have demonstrated retardation of clinical and histological signs and symptoms in experimentally induced OA and other forms of arthritis. As an important factor in cartilage, the regulation of inducible nitric oxide synthase (iNOS) expression and activity, and the effects of NO are reviewed, especially in relation to the pathogenesis of OA. PMID- 17853005 TI - Prevalence of hepatitis B and C markers in glomerular diseases. AB - OBJECTIVE: To study the prevalence of hepatitis B and C viruses in patients with glomerulonephritis (Gn). Material and methods. This was a retrospective study of 89 patients (36 females, 53 males) diagnosed with Gn. Infection with hepatitis B and C was studied by means of serological methods; if patients presented hepatitis C antibodies, the presence of viral RNA in serum was detected by means of quantitative polymerase chain reaction. The control group comprised 59,546 first-time blood donors. RESULTS: None of the patients were positive for hepatitis B surface antigen (HBsAg). In the control group there were 168 HBsAg positives. The prevalence of HBsAg in the control group (0.28%) was not significantly different (p = 0.614) from that in the patient group. Four patients with Gn were positive for hepatitis C virus (HCV) antibodies, and in three of these RNA HCV was also positive. The histological diagnoses in the four cases with HCV antibodies were: focal and segmental glomerulosclerosis; crescentic IgA nephropathy; diffuse proliferative Gn; and membranous Gn. The first three patients also presented other pathologies potentially linked to Gn, namely left renal agenesis, heavy alcohol intake/chronic liver disease and HIV seropositivity, respectively. Only the patient with membranous Gn, in whom other causes were disregarded, received antiviral treatment, although RNA HCV remained positive. In the control group, 141 cases were positive for HCV antibodies (prevalence 0.24%). The prevalence in the study group was significantly higher (p < 0.001). CONCLUSION: HCV is more prevalent in patients with Gn than in those without, and this is the opposite of the situation with HBsAg. PMID- 17853006 TI - Validity of a self-administered questionnaire, with reference to a clinical stress urinary incontinence test. AB - OBJECTIVE: To estimate the criterion validity of a self-administered questionnaire on urinary incontinence (UI) using a clinical stress UI test as reference. MATERIAL AND METHODS: A total of 4710 women aged 20-59 years randomly selected from the municipalities of Aarhus and Randers (Denmark) participated in a population survey on UI. A sub-sample of 96 women stratified by the duration and frequency of UI answered an assisted, self-administered questionnaire concerning UI during the preceding 6 months. Subsequently, a clinical stress UI test was performed with the researchers being blinded with regard to the questionnaire information. RESULTS: Based on the clinical stress test and questionnaire, 22 (22.7%) and 21 women (21.6%) had stress UI, respectively. UI occurring in more than drops and UI lasting for > 4 weeks were found to be adequate predictors of UI (odds ratio 8.9 and 4.6; p < 0.001 and p < 0.05). Regarding all forms of UI, the agreement between the stress UI test result and the questionnaire data ranged from 51.0% to 77.1%. The probability of finding a positive stress UI test was 62% among women who answered that UI had lasted for > 4 weeks and occurred in more than drops, compared to 22.9% in the total study group. The sensitivity and specificity of the stress UI test among women in whom UI lasted for > 4 weeks and occurred in more than drops were 22.7% and 95.9%, respectively. CONCLUSIONS: These findings suggest that there is a greater probability of finding severe UI if the women have experienced it in more than drops and it has lasted for > 4 weeks and it is therefore necessary to estimate the degree of incontinence further by means of a stress UI test. In contrast, women who experienced UI in less than drops and for a duration of < 4 weeks only suffered from a very mild degree of UI. PMID- 17853007 TI - Irrigation with isoproterenol during ureterorenoscopy causes no systemic side effects. AB - OBJECTIVE: Ureterorenoscopy causes complications that may be related to high intrarenal pressures generated during irrigation. Endoluminal isoproterenol administration has been shown to reduce pelvic pressure in pigs. The objective of this study was to investigate possible systemic side-effects of isoproterenol irrigation during ureterorenoscopy in humans. MATERIAL AND METHODS: Seven patients undergoing ureterorenoscopy due to renal stone disease were included. A 5-Fr catheter was retrogradely placed in the renal pelvis for pressure measurements. Prior to irrigation with isoproterenol (0.1 microg/ml), ureterorenoscopy was performed with saline irrigation. Renal pelvic pressure, blood pressure and heart rate were measured before and after isoproterenol irrigation. Venous blood was drawn for isoproterenol measurements. RESULTS: Endoluminal isoproterenol irrigation produced no changes in mean heart rate (HR) or mean arterial pressure (MAP). MAP (+/- SEM) was 56 (2.7) mmHg during saline irrigation and 58 (+/- 2.4) mmHg during isoproterenol irrigation. HR was 60 (+/- 4) beats/min before and 61 (+/- 4) beats/min during isoproterenol irrigation. Neither the difference in MAP = 0.10) nor the difference in HR (p = 0.23) were significant. Pelvic pressure was significantly lower during isoproterenol irrigation [19 (+/- 3) mmHg] compared to saline irrigation [35 (+/- 2.6) mmHg] (p = 0.0006). Pelvic pressure reached very high levels (> 300 mmHg), especially during injection of contrast medium. CONCLUSION: Endoluminal isoproterenol irrigation during ureterorenoscopy causes no cardiovascular side-effects and the drug may reduce renal pelvic pressure. PMID- 17853008 TI - Efficacy of tamsulosin in medical expulsive therapy for distal ureteral calculi. AB - OBJECTIVE: To evaluate the potential role of tamsulosin in the medical treatment of distal ureteral stones. MATERIAL AND METHODS: Ninety patients with symptomatic distal ureteral calculi were enrolled. They were randomly divided into two groups: Group A (n=45) received diclofenac 100 mg on demand for 4 weeks plus levofloxacin 250 mg daily for the first week and were well hydrated; and Group B (n=45) received the same therapy plus tamsulosin 0.4 mg/daily for 4 weeks. Abdominal ultrasound scans and KUB X-rays were performed weekly. Stone expulsion rates, time to expulsion, pain episodes and analgesic usage were determined. Intervention by means of shock-wave lithotripsy (SWL) or ureteroscopy was evaluated. RESULTS: The stone expulsion rate was 51.1% for Group A, compared to 88.9% for Group B (p=0.001). The average time to expulsion was 12.53+/-2.12 days for Group A and 7.32+/-0.78 days for Group B (p=0.04). The number of pain episodes was significantly lower in Group B and mean use of analgesics was lower for Group B (0.14+/-0.5 vials) than Group A (2.78+/-2.7 vials). Twenty-two patients in Group A failed to pass their stones after 4 weeks but only five in Group B. Of the patients who were not stone-free, 19 were treated with SWL and eight underwent ureteroscopy. CONCLUSION: Our study reveals the efficacy of tamsulosin for the treatment of distal ureteral stones. Tamsulosin should be added to the standard medical approach for treating these stones. PMID- 17853009 TI - Short-term effect of simvastatin treatment on inflammatory parameters in peritoneal dialysis patients. AB - OBJECTIVE: Increased serum pro-inflammatory cytokine levels are associated with an increased mortality rate in end-stage renal disease (ESRD) patients. Statins decrease cardiovascular mortality and serum C-reactive protein (CRP) levels in hemodialysis patients. As the anti-inflammatory effect of statins has not previously been studied in peritoneal dialysis (PD) patients with a non inflammatory status, we wanted to investigate the anti-inflammatory effect of simvastatin in these patients. MATERIAL AND METHODS: Forty-eight PD patients were randomly allocated to either simvastatin treatment (n=25) or placebo (n=23). Patients in the active-treatment group received simvastatin 20 mg/day for 1 month. At baseline and after 1 month of treatment, blood samples were drawn and high-sensitivity CRP, interleukin-6, tumor necrosis factor (TNF)-alpha and plasma lipid profiles were determined. These parameters were compared between the groups at baseline and at the end of the study period. RESULTS: Twenty-five subjects in the treatment group and 20 in the placebo group completed the study. Three patients in the placebo group were excluded from the study due to the occurrence of bacterial peritonitis during the study period. Clinical characteristics and baseline parameters were similar in both groups. Serum total and low-density lipoprotein cholesterol levels, and triglyceride and serum TNF-alpha levels decreased significantly compared to baseline in the treatment group; there were no corresponding differences in the placebo group. CONCLUSIONS: Simvastatin decreased the serum TNF-alpha level in PD patients with a non-inflammatory status. A decrease in the TNF-alpha level could be one of the possible mechanisms of the anti-atherogeneic effect of simvastatin. We suggest that different treatment strategies aimed at decreasing serum cytokine levels could be evaluated to decrease cardiovascular morbidity and mortality in the dialysis population. PMID- 17853010 TI - Prostate biopsy in Switzerland: a representative survey on how Swiss urologists do it. AB - OBJECTIVE: The procedure of prostate biopsy is often performed but has not been standardized. Therefore, a survey of all urologists in Switzerland was carried out to investigate indications, patient preparation and technique with regard to transrectal prostate biopsy. MATERIAL AND METHODS: A questionnaire was mailed to all 178 urologists working in Switzerland, either as self-employed urologists (SEUs) or as employed urologists at a hospital (EUHs), i.e. a teaching centre. RESULTS: The questionnaire was returned by 133 urologists (75%). Eighty-seven of the respondents (65%) are SEUs and 46 (35%) work as EUHs. If digital rectal examination (DRE) raises suspicion of cancer, 129 urologists perform a biopsy. A serum prostate-specific antigen (PSA) level of 4 ng/ml is used as a cut-off value by 84% of respondents (SEUs 83%, EUHs 87%). A fluoroquinolone antibiotic is prescribed by 126 of the respondents. Fifty-nine percent of respondents (SEUs 52%, EUHs 72%) are offering periprostatic injection of a local anaesthetic drug. At the initial biopsy, 24% of respondents (SEUs 30%, EUHs 13%) obtain six cores, 45% (SEUs 37%, EUHs 61%) 8-10 and 17% (SEUs 18%, EUHs 15%) > or =12. The subsequent procedure performed after two negative biopsy sessions varies considerably. CONCLUSIONS: This survey provides an insight into the practice pattern of urologists in Switzerland concerning prostate biopsy. For almost all urologists, a positive DRE is an indication for prostate biopsy. The majority use a serum PSA level of 4 ng/ml as a cut-off value. A fluoroquinolone is the antibiotic of choice. Periprostatic nerve block is the commonest form of anaesthesia. Most urologists take 8-10 cores per biopsy. PMID- 17853011 TI - Completeness and correctness of registration of renal pelvic and ureteral cancer in the Swedish Cancer Registry. AB - OBJECTIVE: To study the completeness and correctness of the Swedish Cancer Registry (SCR) for renal pelvic and ureteral carcinomas diagnosed in western Sweden. MATERIAL AND METHODS: We performed a retrospective clinical and histopathological study of 939 patients in the SCR with a diagnosis of a renal pelvic or ureteral carcinoma between 1971 and 1998 and of 54 patients with a diagnosis of tumors in multiple locations in the urinary tract. In addition, we reviewed our earlier bladder cancer studies to assess whether patients with upper urinary tract tumors had been notified to the SCR. RESULTS: There were 68 false positive patients (7.2%) out of 939 in the SCR. The commonest diagnoses were other urological malignancies (n=46) and no malignancy at all (n=15). There were five false-positives (9.3%) out of 54 patients in the file with tumors in multiple locations. Twenty-eight patients with renal pelvic or ureteral carcinoma were identified in our earlier studies but not found in the SCR. Most discrepancies were attributable to inadequate or missing notification by the urologist and registration errors. CONCLUSIONS: The completeness and correctness of the registration of renal pelvic and ureteral carcinomas are unsatisfactory but in line with registries for some other primary sites. The notification of upper urinary tract tumors among patients with a history of bladder cancer was poor, in particular in patients not treated with surgery. Improved communication between reporting sources and the registry is needed. Clinical and histopathological reviews seem necessary in studies based on the SCR. PMID- 17853012 TI - Circadian rhythm of blood pressure in patients with benign prostatic hyperplasia. AB - OBJECTIVE: Nocturia, a common and bothersome symptom of benign prostatic hyperplasia (BPH), may cause sleep disturbances. Patients with nocturia may have difficulty returning to their normal sleep after repeated episodes of waking and voiding. Therefore, nocturia may have an impact on the circadian rhythm of blood pressure (BP). The association between nocturia and the circadian rhythm of BP was investigated in this study. MATERIAL AND METHODS: A total of 100 male patients who had been diagnosed with BPH and 53 healthy male subjects were included in the study. Nocturnal urinary frequency was assessed by means of a questionnaire and recorded in both groups. Ambulatory BP monitoring was performed in all patients over a 24-h period. RESULTS: Patient characteristics and laboratory parameters were similar in both groups. Seventy-five patients (75%) in the BPH group and 20 subjects (37.7%) in the control group were non-dippers, i.e. they did not have a normal nocturnal fall in BP, and this difference was statistically significant (p=0.001). Eighty-nine patients in the BPH group and 13 in the control group had nocturia. Seventy-one patients (79.8%) with nocturia were non-dippers and the difference compared to the patients without nocturia in the BPH group was significant (p=0.003), whereas four patients with nocturia (30.8%) were non-dippers in the control group. CONCLUSIONS: Our findings indicate that non-dipping was more prevalent in elderly men with BPH and nocturia. BPH and nocturia may be etiological factors in the pathogenesis of non-dipping, which is an indicator of early cardiovascular disease. Further studies must focus on this relationship and, especially, on whether treatment of nocturia and BPH helps to treat non-dipping or not. PMID- 17853013 TI - Impalpable testis: laparoscopy or inguinal canal exploration? AB - OBJECTIVE: There is great controversy regarding the best approach to impalpable testis. In this retrospective study we evaluated the accuracy of intraperitoneal laparoscopy, inguinal canal exploration and ultrasound in the diagnosis of impalpable testis. MATERIAL AND METHODS: Over a 2-year period (2004-06), 76 patients with a diagnosis of uni- or bilateral clinically impalpable testis were referred to our center. A preoperative ultrasound evaluation was done and all patients underwent intraperitoneal laparoscopy. An inguinal canal incision and exploration was done in all cases except for patients with high intra-abdominal testes (> 2 cm above the internal ring), for whom laparoscopic dissection, mobilization and orchidopexy were necessary. RESULTS: The mean age of the patients was 15.36 years (range 1-39 years). The undescended testis (UDT) was right-sided in 25% of patients, left-sided in 41% and bilateral in 34%. Intraperitoneal laparoscopy, inguinal canal exploration and ultrasound detected 70.6%, 78.4% and 15.6% of testes, respectively. CONCLUSIONS: Laparoscopy changed the management protocol of impalpable UDT in only 21% of cases. Inguinal canal exploration alone was sufficient in the majority of our cases. We recommend laparoscopy for those patients with impalpable UDT in whom an initial inguinal canal exploration proves negative. PMID- 17853014 TI - Medication discrepancy: a concordance problem between dialysis patients and caregivers. AB - OBJECTIVES: Extensive drug utilization, and non-concordance between the patient and the caregiver about prescriptions and actual medicine intake, are associated with the risk of non-adherence to medication as well as medication-related illness. To achieve reliable estimates of drug use, it is important to consider the patient's self-reported drug utilization as well as to consult his/her medical record. The present multicentre study was conducted with the aim of examining the self-reported drug consumption of dialysis patients and its congruence with medical records. MATERIAL AND METHODS: Consumption of pharmaceutical agents was recorded by 204 patients undergoing haemo- or peritoneal dialysis at 10 Swedish clinics. Drug record discrepancies were identified by comparing the self-reported use of prescribed medicines with the subsequently obtained medication lists. RESULTS: The median drug intake was 11 prescribed medicines and by including on-demand drugs this increased to 12. Discrepancies between the self-reported use of prescribed drugs and the medical record were prevalent in 80.4% of cases, with a median of three discrepancies per patient. CONCLUSIONS: Dialysis patients have an extensive need for medication but there is an undesirable deviation between consumption and prescription. A single medication list, accessible for the patient and for all prescribers, is a possible solution to achieve concordance but other measures, such as analysis of the reasons for discrepancy and tailored measures, would also benefit concordant medicine-taking. PMID- 17853015 TI - Seasonal changes in symptom score and uroflowmetry in patients with lower urinary tract symptoms. AB - OBJECTIVE: To determine whether subjective or objective seasonal changes occur in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). MATERIAL AND METHODS: A total of 31 patients with LUTS were observed for >5 years. Their International Prostate Symptom Score (IPSS), quality of life (QOL) score, maximum flow rate (Qmax), voided volume (VV) a nd post-void residual (PVR) we re measured every month. RESULTS: Total IPSS, QOL, VV or PVR did not show any seasonal changes between the three seasons: summer (hot season: June to September); winter (cold season: December to March); and spring and fall (comfortable season: April, May, October and November). Furthermore, when the IPSS was examined by dividing it into storage symptoms (frequency, urgency and nocturia) and voiding symptoms (incomplete emptying, intermittency, weak stream and straining), no significant seasonal changes were detected. Only Qmax showed a significant seasonal change, being higher in both the cold season (median 10.4 ml/s) and the comfortable season (median 10.1 ml/s) than in the hot season (median 9.4 ml/s). CONCLUSIONS: It has generally been thought that LUTS worsen in winter. Our results indicate that the IPSS and the QOL score remain nearly constant if they are determined regularly over an extended period of time. Qmax may however be influenced by seasonal changes in temperature. PMID- 17853016 TI - Open partial nephrectomy for imperative and elective indications comparison of peri-operative data and long-term follow-up. AB - OBJECTIVE: To report the outcome of nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) with elective and imperative indications, with analysis of complications, renal function and long-term oncological follow-up. MATERIAL AND METHODS: We analyzed 91 patients undergoing NSS for RCC, 26 with imperative and 65 with elective indications. Variables analyzed included patient age and gender, comorbidities per patient and preoperative renal function. Pathological features included tumor size, WHO 2002 stage and grade. Peri- and postoperative data included complication and re-intervention rates, tumor recurrence and the mortality rate. RESULTS: RCC was found in 81.3% of cases in the imperative group and in 73.9% in the elective group. Median tumor size was 3.2 and 2.5 cm (p = 0.02) in the imperative and elective groups, respectively. Operation time was longer in the imperative group (p < 0.01). There was no difference between the two groups regarding intraoperative complication rate (p = 0.37), whereas postoperative complications occurred more frequently in the imperative group (p = 0.02). The median follow-up period was 48 months for both groups. Mean serum creatinine during follow-up was significantly higher in the imperative group (238.4 vs 97.2 Micromol/L). However, no patient required hemodialysis. There was no local recurrence or tumor-specific death in either group. CONCLUSIONS: NSS for RCC is a reasonable treatment option for patients with an imperative indication as it prevents the need for hemodialysis as well as ensuring excellent oncological follow-up. A higher postoperative complication rate has to be balanced against improved quality of life. PMID- 17853017 TI - Prostate cancer: to scan or not to scan for lymph node involvement? AB - OBJECTIVE: When diagnosing lymph node involvement in prostate cancer (PC), the available imaging techniques are considered to be of doubtful value but are still in common use in many institutions because of a lack of better alternatives. To help us choose between methods while we wait for improvements in technologies, we evaluated the performance of ultrasonography (US), CT and MRI. MATERIAL AND METHODS: We reviewed the records of all PC patients who were potential candidates for a surgical staging procedure prior to treatment with intent to cure at Skejby Sygehus, Denmark between 1996 and 2004. In total, 227 patients met our inclusion criteria and 149 were examined with US, 80 with MRI and 71 with CT. The performance of the three modalities was analysed. RESULTS: A total of 50 patients (22%) had lymph node metastases (pN1) and only 12 of these cases (24%) were detected by imaging. US identified all 12 pN1 patients, MRI five and CT did not identify any. Moreover, US missed 28 patients with pN1 metastases, MRI 18 and CT 13. Consequently, US, MRI and CT had sensitivities of 0.3, 0.22 and 0, respectively, while all three modalities had a specificity of 1. The 12 patients identified by imaging had clinically advanced and pathologically aggressive cancers. CONCLUSIONS: Available imaging techniques showed moderate to very low sensitivity. US proved superior to MRI and CT, but should only be applied in high risk patients. In particular, CT can be considered unsuitable for diagnosing pelvic lymph node metastases in PC. PMID- 17853018 TI - Is the pain level of patients affected by anxiety during transrectal prostate needle biopsy? AB - OBJECTIVE: To investigate the effect of anxiety on the pain level of patients during transrectal prostate needle biopsy. MATERIAL AND METHODS: A total of 160 consecutive patients underwent prostate biopsy. Group 1 consisted of 86 patients who received bilateral periprostatic infiltration of 5 cm(3) of 2% lidocaine. Group 2 included 74 patients and they received bilateral periprostatic infiltration of 5 cm(3) of 0.9% saline solution. The Stait-Trait Anxiety Inventory was administered before the biopsy. The patients' mean pain scores were assessed by means of a visual analog scale (VAS) during digital rectal examination, probe insertion and biopsy. RESULTS: The mean age of the patients was 67.8 years (range 46-79 years). When the two groups were compared regarding the level of pain during DRE and probe insertion, no significant differences were found. The mean VAS score for biopsy was significantly lower in Group 1. In Group 1, the mean VAS scores were similar in patients with no and moderate trait anxiety levels. However, the mean VAS score was significantly higher in patients who had severe trait anxiety than in the others (p=0.002). In Group 2, the differences in VAS scores reached statistical significance between no and moderate, no and severe, and moderate and severe trait anxiety levels (p=0.001). When the state anxiety levels were considered, the mean VAS scores were significantly higher in patients with severe state anxiety scores in Groups 1 and 2 (p=0.003 and 0.001, respectively). CONCLUSION: We found a significant relationship between trait and state anxiety levels and pain scores in patients who underwent transrectal prostate needle biopsy. PMID- 17853020 TI - CT of the kidneys: what size are renal cell carcinomas when they cause symptoms or signs? AB - OBJECTIVE: To investigate the size of renal cell carcinomas (RCCs) when they cause macroscopic hematuria or other symptoms and/or signs. MATERIAL AND METHODS: A retrospective review of 232 patients (136 males, 96 females; mean age 68 +/- 11 years; age range 40-90 years) with a diagnosis of RCC was undertaken. Patients were grouped according to the presenting symptoms and/or signs caused by the RCCs. Tumor size was measured on CT images. RESULTS: Of the RCCs, 29% were found incidentally and 71% caused symptoms and/or signs. The incidentally found RCCs measured 4.9 +/- 2.6 cm (range 2-12 cm) and RCCs causing symptoms and signs measured 8.9 +/- 3.2 cm (range 3-18 cm); this size difference was significant (p < 0.001). None of the RCCs causing macroscopic hematuria were <4 cm in size and only 3/165 (2%) of the symptomatic RCCs were <4 cm in size. DISCUSSION: If small (<4 cm) RCCs do not cause symptoms, patients with them will not be referred for CT or any other imaging modality. Therefore, if a 2-cm RCC is found in a patient presenting with macroscopic hematuria, it is unlikely that this small RCC caused the hematuria and another cause of the hematuria must be ruled out. PMID- 17853019 TI - Prognostic significance of proliferation activity and neuroendocrine differentiation to predict treatment failure after radical prostatectomy. AB - OBJECTIVES: Neuroendocrine (NE) cells in prostate cancer may influence tumor cell proliferation in a paracrine fashion. The aims of this study were to clarify the prognostic value of tumor cell proliferation and NE tumor cell differentiation in prostate cancer after radical prostatectomy, and to compare these parameters with each other. MATERIAL AND METHODS: Specimens were pooled from a total of 528 patients treated with radical prostatectomy without neoadjuvant hormonal therapy between 1996 and 2003. NE differentiation (NED) was determined by immunohistochemistry using antibodies directed against chromogranin A (CgA), and was scored as either NE-negative (0-1+) or -positive (2-3+). Tumor cell proliferation was assessed by means of the Ki-67 labeling index (Ki-67 LI). The mean post-surgical follow-up period was 49 months (range 10-116 months). Any subsequent rise in prostate-specific antigen (PSA) level was regarded as reflecting disease progression. The prognostic values of Ki-67 and CgA were comparatively analyzed using multivariate Cox regression. RESULTS: NED was present in 6.1% of tumors. The mean Ki-67 LI was significantly higher in the CgA positive group in comparison with CgA-negative specimens (6.6% vs 5.0%; p=0.029). The Ki-67 LI showed the highest correlations with Gleason score and pathological tumor stage (r=0.31 and r=0.3, respectively). NED was found to have the strongest association with pathological tumor stage (r=0.2). Multivariate analysis determined Gleason score > or =7 (4+3) [hazard ratio (HR) 3.04], NED (HR 1.89), lymph node metastases (HR 1.84), preoperative PSA level>20 ng/ml (HR 1.66), and Ki-67 LI > or = 5% (HR 1.62) to be significant predictors of biochemical progression. CONCLUSION: Our results identify Ki-67 LI and NED as additional prognostic markers after radical prostatectomy. PMID- 17853021 TI - Elastase deposits in the kidney and urinary elastase excretion in patients with glomerulonephritis--evidence for neutrophil involvement in renal injury. AB - OBJECTIVE: Elastase is a key proteolytic enzyme released during polymorphonuclear leukocyte degranulation. There are abundant data of elastase involvement in the development of injury in experimental models of glomerulonephritis (GN), but scant direct evidence of its involvement in human primary GN. The aims of this study were to determine the immunolocalization of elastase deposits in kidney biopsy specimens from patients with primary idiopathic GN, to attempt to correlate the distribution and intensity of deposits with urinary elastase excretion, and to determine clinical markers of renal injury in several types of primary idiopathic GN. MATERIAL AND METHODS: The immunohistochemical localization and intensity of elastase deposits in kidney biopsies, the urinary excretion of leukocyte elastase, and proteinuria and serum creatinine levels were evaluated in 23 patients with primary GN and the associations between these factors were sought. RESULTS: Patients with crescentic proliferative GN had the highest intensity of elastase deposits. In this group of patients, elastase was present in the glomerular endothelium, as well as in the tubular epithelium and interstitium. Patients with a high intensity of elastase deposits within the glomerular endothelium and Bowman's capsule had significantly higher urinary excretion of elastase. Patients with interstitial, mesangial and perivascular elastase deposits had significantly higher serum creatinine than those without. Patients with elastase deposits in the glomerular endothelium and in the interstitium had insignificantly higher proteinuria than those without. CONCLUSION: Our data provide morphological evidence of leukocyte elastase involvement in renal injury occurring in the course of primary idiopathic GN, in particular in the proliferative types. PMID- 17853022 TI - Intravesical self-tying knots in suprapubic catheters: a report of two cases. AB - We present two cases in which intravesical, self-tying knots occurred when the Cystofix catheter was used for suprapubic catheterization in two male boys admitted for hypospadias surgery. This complication of suprapubic catheterization is most likely due to the pigtail end of the catheter, and should be considered when removal is difficult. PMID- 17853023 TI - Herniation of renal pelvis and ureteropelvic junction resulting from superior lumbar triangle hernia. AB - A 79-year-old female admitted as a result of respiratory insufficiency due to pneumonia presented with a painful swelling in the left lumbar region and acute ureteral colic pain. The diagnosis of Grynfeltt's bilateral hernia was made by means of CT, which revealed herniation in the left side of the renal pelvis and proximal ureter. PMID- 17853024 TI - Myosin heavy-chain isoform distribution, fibre-type composition and fibre size in skeletal muscle of patients on haemodialysis. AB - OBJECTIVE: Chronic uraemia is associated with abnormalities in skeletal muscles, which can affect their working capacity. It is also well known that the fibre type composition of skeletal muscles influences endurance, muscle strength and power. In this study we therefore determined the size and distribution of muscle fibres and the myosin heavy-chain (MHC) isoform composition in patients on haemodialysis (HD) in order to establish any differences with values for untrained control subjects. MATERIAL AND METHODS: Muscle biopsies were obtained from the vastus lateralis muscle of 14 non-diabetic patients on HD. The size and distribution of muscle fibres were evaluated using adenosine triphosphate synthase (ATPase) histochemistry, whilst MHC isoform composition was determined in muscle homogenates using sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Values were compared to those for a group of age-, gender- and BMI-matched untrained control subjects. The aerobic work capacity of the patients was also determined. RESULTS: The MHC composition for I, IIA and IIX isoforms was found to be 35.3% +/- 18.2%, 35.9% +/- 7.1% and 28.9% +/- 15.6%, respectively, findings supported by the ATPase histochemically determined fibre-type composition of the vastus lateralis muscle. The mean fibre area of type 1 and 2 fibres was 3283 +/- 873 and 3594 +/- 1483 MICROm2, respectively. The MHC composition and the size of the type 1 fibres of the patients on HD were significantly different from those of the control subjects. CONCLUSIONS: The data demonstrate relatively fewer type 1 and consequently more type 2x fibres, with a corresponding change in MHC isoforms (MHC I and MHC IIX) in the skeletal muscle of patients on HD. Several patients on HD were found to have <15% type 1 (or relative percentage of MHC I) fibres. Such a low percentage of type 1 fibres is very rarely observed in normal untrained subjects. Chronic uraemia more severely affects the composition than the size of fibres. PMID- 17853025 TI - A rational combination of intravesical and systemic agents for the treatment of interstitial cystitis. AB - OBJECTIVE: Interstitial cystitis is a condition with a poorly understood etiology and, consequently, various treatment options have been described in the literature, with a less than optimal outcome. The aim of this study was to examine the role of a combination of intravesical hydrocortisone and heparin, together with oral bladder sedatives and systemic triamcinolone, for the treatment of interstitial cystitis. MATERIAL AND METHODS: A total of 26 patients who were diagnosed as having interstitial cystitis were treated with weekly intravesical hydrocortisone (200 mg) and heparin (25,000 IU) in physiological saline for 6 weeks. In addition, they were given oral bladder sedatives such as oxybutynin or tolterodine. Ulcerative, refractory and recurrent cases were treated with intramuscular triamcinolone (40 mg) weekly for 6 weeks. RESULTS: All patients experienced an improvement in symptoms within 48 h of their first intravesical instillation. While 19 patients (73%) experienced almost complete pain relief, five of the remaining seven patients improved with intramuscular triamcinolone. Frequency reduced from a mean of 23.2 to 10.9 voids per day and was acceptable in 21 patients (80%). Six patients (23%) had a relapse of symptoms in the form of pain and were treated satisfactorily by means of intramuscular triamcinolone. The mean duration of follow-up was 18.3 months. CONCLUSION: A combination of intravesical hydrocortisone and heparin, along with oral bladder sedatives and systemic steroids, has been used with encouraging results in a small group of patients with interstitial cystitis. PMID- 17853026 TI - Penile involvement in Henoch-Schonlein purpura with good prognosis. AB - Henoch-Schonlein purpura (HSP), the commonest vasculitis in children, occurs most frequently between the ages of 4 and 6 years. We report the case of a 3-year-old boy with an otomastoiditis who was treated with cephalosporin and corticosteroids following a typical purpuric skin rash diagnosed as HSP. The patient also developed an acute occurrence of impairment of the glans, prepuce and penis 4 days after recovery that completely disappeared after a further 2 days, with the cutaneous rash subsiding on discharge from hospital. PMID- 17853027 TI - Chronic prostatitis/chronic pelvic pain syndrome: symptoms are aggravated by cold and become less distressing with age and time. AB - OBJECTIVES: To evaluate how age and the duration of the condition influence the distress caused by the chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and to study how heat and cold influence the symptoms associated with CP/ CPPS as reported by patients afflicted with the condition. MATERIAL AND METHODS: Forty eight men (median age 50 years; age range 27-70 years) who had suffered from CP/CPPS for a duration ranging from 18 months to 40 years were included in the study. The evaluation included determination of the serum prostate-specific antigen level, the National Institutes of Health's Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Prostate Symptom Score (IPSS). RESULTS: The mean NIH-CPSI score was 23.0 +/- 4.8. The mean IPSS was 14.3 +/- 7.2. Dysuria was reported by 30 men (63%) and ejaculatory pain by 22 (48%). Men with dysuria had painful ejaculations more often (60%) than men without (22%) (p <0.01). There was a strong negative correlation between age and the NIH-CPSI quality of life (QOL) score (correlation coefficient 0.646; p < 0.001). Independent of age, the duration of the disease also correlated with the NIH-CPSI QOL score (correlation coefficient -0.48; p < 0.02). The total NIH-CPSI score did not correlate with either age or the duration of the disease. Nearly every other man stated that the disease had started in association with a specific event, which for 15 men (31%) included exposure to cold. Forty men (83%) reported that cold caused symptom aggravation and/or induced a relapse. Thirty men (63%) stated that taking a hot bath and 22 (46%) reported that spending time in a hot climate decreased the symptoms. CONCLUSIONS: Age, as well as the duration of the condition, influenced the distress induced by CP/CPPS, suggesting an improved coping ability with time as well as age. The ambient temperature appears to play a role as cold was frequently reported as causing symptom aggravation and heat was often reported to be ameliorating. The mechanisms behind this association between CP/CPPS and temperature as well as the correlation between ejaculatory pain and dysuria require further study. PMID- 17853028 TI - Neuroendocrine differentiation of localized prostate cancer during endocrine therapy. AB - A 74-year-old male was treated with endocrine therapy for localized prostate cancer. After 25 months he complained of a swollen neck, and was diagnosed with prostate cancer with lymph node metastasis of neuroendocrine differentiation. Neuroendocrine differentiation without elevation of conventional tumor markers is rare during the initial recurrent course of localized prostate cancer. PMID- 17853029 TI - Local defense systems in the prepuce. AB - OBJECTIVE: Urinary tract infection (UTI) is a common bacterial infection in children. Circumcision reduces the incidence of UTI, and prevents preputial colonization with uropathic bacteria in childhood. However, there is insufficient information about the reason(s) why such colonization tends to occur in prepucium skin. MATERIAL AND METHODS: We evaluated some of the humoral and cellular defense systems in the prepucium skins of 30 boys (age range 6 months to 5 years). We measured the expressions of Langerhans cells, mast cells, T lymphocytes, IgA, IgG and IgM in the prepuce and compared them with those in normal skin. Tissues obtained during circumcision were divided into two groups. In the first group, sections were stained with hematoxylin-eosin and toluidine blue. Immunohistochemical reactions were performed on paraffin-embedded tissue by means of the avidin-biotin-peroxidase complex method. The antibodies used were S-100 for Langerhans cells and CD8 and CD4 for T lymphocytes. In the second group, frozen sections were stained for IgA, IgG and IgM using an immunofluorescence method. RESULTS: The distribution of mast cells and IgG positivity was similar to that of normal skin. Langerhans cells were increased in prepucium skin (p<0.05), whilst only a few CD4 T lymphocytes were observed around the perivascular area and no expression of CD8 was observed in the prepucium and normal skin. CONCLUSIONS: The increase in Langerhans cells in prepucium skin may be the result of continuous stimulation of bacteria found in the periurethral area, and the absence of CD8 may help the colonization of uropathic bacteria. PMID- 17853030 TI - Laparoscopic radical prostatectomy: surgical, oncological and functional outcomes. AB - OBJECTIVE: To report the first results of laparoscopic radical prostatectomy (LRP) at our institution. MATERIAL AND METHODS: The surgical, functional and oncological outcomes of all patients who underwent LRP at Helsinki University Central Hospital between May 2002 and May 2006 were prospectively evaluated. The first eight patients were operated transperitoneally and the next 72 extraperitoneally. RESULTS: The mean operative time was 328+/-73 min (range 210 510 min). The mean estimated blood loss was 769+/-906 ml (range 50-5500 ml), and 18 patients (22.5%) had transfusions. The mean catheterization time was 13.2+/ 4.0 days (range 9-35 days). Mean hospital stay was 5.7+/-3.1 days (range 3-15 days). Nineteen patients (23.8%) had perioperative complications. The conversion rate to open surgery was 11.3% and 6.3% required an immediate re-operation. Three anastomotic strictures (5.7%) and two cases of ileus (3.8%) were observed. The cancer was intracapsular (pT1-2) in 68 patients (85.0%) and extracapsular (pT3-4) in 12 (15.0%). Positive surgical margins were noted in 20 patients (25.0%) in total: 17.6% of pT1-2 cases and 66.7% of pT3-4 cases. Prostate-specific antigen recurrence (> or =0.2 ng/ml) was noted in 5/53 patients (9.4%), who were followed for >12 months. The continence rate (no daily pad use) was 86.8% and the potency rate was 34.6% at 12 months. CONCLUSIONS: The surgical, functional and oncological results of our first LRPs compare fairly well with the early experience of others. LRP is feasible outside high-volume centers but the learning curve is expected to be long. PMID- 17853031 TI - Clinical importance of intratumoral and normal renal parenchymal inflammatory cell infiltration in renal cell carcinoma. AB - OBJECTIVE: To assess the relationship between inflammatory cell infiltration and tumor type, stage and grade, the presence of multifocality and survival in tumors and in tumor-free normal parenchyma. MATERIAL AND METHODS: A total of 99 patients who underwent radical nephrectomy for renal cell carcinoma (RCC) between 1995 and 2001 and were subsequently followed up were included in the study. Formalin fixed, paraffin-embedded tissues from the patients were reassessed by a pathologist and inflammation in both tumor and normal renal tissue was scored using a five-point scale. We evaluated the relationship between these scores and tumor type, stage, grade, the presence of multifocality and survival. RESULTS: There were positive correlations between tumor grade and both the intratumoral inflammation score (IIS) and the extratumoral inflammation score (EIS) (p=0.001 and 0.01, respectively). There were no relations between pathological stage and either the IIS or EIS. We found higher multifocality rates in patients who died because of metastasis than those who survived (p=0.002). The EIS was 1.76+/-1.54 in the non-multifocality group and 2.64+/-1.15 in the multifocality group and this difference was statistically significant (p=0.03). There was no statistically significant relationship between the IIS and multifocality. Oncocytomas and chromophobe carcinomas did not show inflammatory infiltrates in either tumors or normal renal tissue. CONCLUSIONS: Higher EIS and IIS are associated with increasing tumor grade and a higher EIS is associated with multifocality in RCC. We propose to evaluate tumor tissue and normal renal parenchyma for the presence of inflammatory infiltration in RCC. PMID- 17853032 TI - Chronic abacterial prostatitis and cold exposure: an explorative study. AB - OBJECTIVE: Chronic abacterial prostatitis/pelvic pain syndrome (CP/CPPS) is characterized by pain, voiding and sexual dysfunction persisting fo r> 3 months. The symptoms tend to occur in relapses of varying length. To evaluate what causes a relapse and what precautions patients with CP/CPPS undertake to avoid a relapse and/or aggravation of symptoms, individual semi-structured interviews were performed. MATERIAL AND METHODS: Information was obtained from semi-structured in depth interviews with 10 selected men with CP/CPPS (mean age 44 years; 30-62 years). The interviews were transcribed and analysed according to Girorgi's phenomenological method as modified by Malterud. RESULTS: CP/CPPS tended to start in connection with a specific event involving cold exposure, suggesting cold as an initiating stimulus for CP/CPPS. The informants also reported that cold exposure caused aggravation of symptoms and provoked their relapse. Sitting on cold objects, spending time in cold, damp or windy surroundings and walking on a cold floor were provocative and thus were avoided. The exposure did not have to be either prolonged or intense. Heat applied to the perineum, as well as spending time in a warmer climate, gave relief from symptoms. CONCLUSIONS: It appears that cold is one of the factors that can trigger a process resulting in CP/CPPS. The fact that cold also causes aggravation of symptoms and can initiate a relapse was evident, as was the fact that symptoms could be relieved by heat. The connection between cold and symptom aggravation is well known among clinicians but has not previously been studied in a systematic way. The fact that cold, in a susceptible man, can initiate a process resulting in CP/CPSS has not been reported before. Studies aimed at elucidating the mechanisms behind this phenomenon are warranted. Reflex vasoconstriction in a susceptible individual is a possible cause. PMID- 17853033 TI - A novel technique of bulbourethral sling for post-prostatectomy incontinence. AB - OBJECTIVE: The treatment of post-prostatectomy incontinence (PPI) can be challenging. Although many injectable materials have been used to treat this problem, the results are at best unsatisfactory. Fixation of an artificial urinary sphincter has been the gold standard of care for patients with PPI for many years. In the last decade there has been a revival of male sling techniques, involving either a fixed or dynamic compressive effect. Herein, a technique for the correction of PPI is described which involves minimal incursion of exogenous material and has excellent cost-effectiveness. MATERIAL AND METHODS: A total of 23 patients underwent a bulbourethral sling procedure using mesh suspended from the anterior abdominal wall for the management of PPI. The technique is performed under spinal anesthesia and utilizes knitted polypropylene mesh, which is fastened by three pairs of sutures. A modified Stamey needle is used for transferring nylon sutures to the suprapubic wound. The sutures are tied in front of the rectus sheath, utilizing intraoperative urodynamic guidance. A 12 F suprapubic tube is utilized as a pressure channel for monitoring vesical pressure and sling tension. RESULTS: Twenty patients were completely dry at the last follow-up, one was greatly improved and in two the treatment was considered a failure. The median follow-up period was 9 months (range 6-24 months). No urethral erosion has been reported thus far. Morbidity in the form of perineal pain and limited ambulation in the first few days after surgery were reported. Five patients had scrotal and penile numbness which continued for an average of 3 months. CONCLUSIONS: The mesh sling technique described herein is efficient and cost-effective. It yielded promising results in this study, which involved a short-term follow-up period and a limited number of patients. More cases are being enrolled and a study involving a longer follow-up period is underway. PMID- 17853034 TI - Three-dimensional stereology as a tool for evaluating bladder outlet obstruction. AB - OBJECTIVE: In a pilot study we evaluated whether implementation of a novel 3D stereologic technique can prove that bladder outlet obstruction (BOO) is associated with morphologic changes in the bladder wall. MATERIAL AND METHODS: Ten males (mean age 69.7 years; range 58-84 years) with lower urinary tract symptoms (LUTS) suggestive of BOO and five controls (mean age 48.6 years; range 43-53 years) without LUTS were studied. All participants underwent a full examination, including determination of the International Prostate Symptom Score, laboratory analysis and a urodynamic evaluation. A cold-cup biopsy, taken during cystoscopy, was stereologically evaluated to determine the smooth muscle cell volume and the fractions of collagen and smooth muscle using light and electron microscopy. RESULTS: The collagen fraction was higher in patients than in controls (probably because the patients were older). There was no relation between the Abrams-Griffiths number and either the interstitial fraction or the collagen fraction. Furthermore, the results suggest an age-associated effect of morphological changes in the bladder wall. The smooth muscle volume also showed no relationship with the severity of obstruction. CONCLUSIONS: This pilot study shows that, even with the implementation of subtle morphometric techniques, there seems to be no relationship between the severity of BOO and bladder wall morphology. It is possible that interstitial collagen in the bladder wall increases with age. It seems that bladder wall morphology is heterogeneous within small areas. PMID- 17853035 TI - Comparison of anxiety between patients with mixed incontinence and those with stress urinary incontinence. AB - OBJECTIVE: Some authors insist that patients with mixed incontinence (MI) suffer from more anxiety than those with pure stress urinary incontinence (SUI) due to the added emotional stress caused by various symptoms of an overactive bladder. We objectively evaluated and compared the degree of anxiety between the two groups. MATERIAL AND METHODS: Among 172 patients who presented with urinary incontinence, 118 showed MI and 54 SUI. They were surveyed regarding their anxiety using the Beck Anxiety Inventory (BAI) questionnaire. RESULTS: The mean BAI score was 12.0+/-8.8 in the MI group and 7.8+/-5.2 in the SUI group and this difference was statistically significant (p<0.05). CONCLUSIONS: This study provides objective evidence that patients with MI have a higher degree of anxiety than those with pure SUI. Therefore, we suggest that doctors should pay more attention to anxiety symptoms when caring for patients with MI. PMID- 17853036 TI - Lornoxicam in extracorporeal shock-wave lithotripsy; comparison with tenoxicam and placebo in terms of analgesic consumption. AB - OBJECTIVE: To assess the analgesic efficacy of lornoxicam and compare it with that of tenoxicam in patients undergoing extracorporeal shock-wave lithotripsy (ESWL) for renal stones. MATERIAL AND METHODS: The study was carried out in a randomized, double-blind fashion and involved 60 patients (American Society of Anesthesiologists physical status I-II) undergoing ESWL who were divided into three groups. Patients in the placebo group (n = 20) received saline and those in the lornoxicam group (n = 20) received lornoxicam 8 mg intravenously 60 min before the procedure. In the tenoxicam group, patients (n = 20) received tenoxicam 20 mg intravenously at the same time point. All patients were started on patient-controlled i.v. meperidine analgesia during the procedure. The effectiveness was assessed by using a visual analog scale (VAS) and by calculating the total analgesic consumption of meperidine during the procedure. Arterial blood pressure, oxygen saturation, and respiratory rate were recorded throughout the procedure; nausea and vomiting, agitation, and respiratory depression were assessed. RESULTS: Compared with patients in the placebo group, patients in the lornoxicam and tenoxicam groups received smaller doses of meperidine at all time points (p < 0.05). After 30, 45, and 60 min of ESWL, patients in the lornoxicam group required significantly smaller doses of meperidine than those in the tenoxicam group (p < 0.05). Patients in the placebo group showed higher VAS scores than those in the lornoxicam and tenoxicam groups at 15, 30 and 60 min. The VAS score in the lornoxicam group was lower than that in the tenoxicam group at 15, 30, and 45 min, but the difference between the groups was statistically significant only at 45 min (1 and 3, respectively; p < 0.05). CONCLUSION: In patients undergoing ESWL the i.v. administration of a single dose of 8 mg lornoxicam provides significantly better pain control compared with tenoxicam 20 mg and placebo, without increasing adverse side effects. PMID- 17853037 TI - Primary adenocarcinoma of the rete testis: diagnostic problems and therapeutic dilemmas. AB - We describe a rare case of a malignant tumour of the rete testis which was diagnosed incidentally during scrotal surgery for an apparently benign left hydrocele. Adenocarcinoma of the rete testis is a malignancy with a poor prognosis. The beneficial role of prophylactic retroperitoneal lymphadenectomy is controversial due to the extremely low number of reported cases and the occasional description of primary lymphatic spread outside the retroperitoneal space. PMID- 17853038 TI - Prognostic factors predicting successful response to sildenafil after radical cystoprostatectomy. AB - OBJECTIVES: To assess the efficacy and safety of sildenafil citrate in the management of erectile dysfunction (ED) following radical cystectomy (RC) and to define the different prognostic factors predicting the response to sildenafil in such a challenging group of patients. MATERIAL AND METHODS: One hundred patients with ED following RC participated in an open-label, non-randomized, prospective, dose-escalation study. The median age of the patients was 53 years and the mean period after RC was 80.7 +/- 54.8 months. The study duration was 12 weeks, comprising a 4-week run-in period followed by two active treatment periods of 4 weeks each with 50 and 100 mg of sildenafil. Patients were assessed by means of the International Index of Erectile Function (IIEF) questionnaire at baseline and after each treatment period. At the end of the study, the Global Efficacy Assessment Question was used to evaluate treatment satisfaction. Factors affecting the patient's response to sildenafil were assessed by means of uni- and multivariate analysis. RESULTS: The entire study group was suffering from severe ED at baseline, with a mean erectile function (EF) domain score of 6.5 +/- 0.93. EF scores improved to 12.2 +/- 7.76 and 18 +/- 10.3 with 50 and 100 mg of sildenafil, respectively. Sildenafil therapy significantly improved the ability of many patients to achieve and maintain an erection. The mean scores for question 3 of the IIEF were 1 +/- 0.14, 2.1 +/- 1.4 and 3 +/- 1.8 at baseline and with 50 and 100 mg of sildenafil, respectively, while the corresponding scores for question 4 were 1 +/- 0.10, 1.9 +/- 1.35 and 3 +/- 1.85. The satisfaction rate was 54%. The response was dose-dependent but the incidence of adverse effects increased from 6% with 50 mg of sildenafil to 34% with 100 mg. In univariate analysis, tumor histology and grade and postoperative partial tumescence were found to significantly impact the patient's response to sildenafil. In multivariate analysis, postoperative partial tumescence was the only independent predictive variable. CONCLUSIONS. Sildenafil was found to be a safe and satisfactory treatment for post-RC ED. The effect was dose-related. Patients with postoperative partial tumescence were the best responders. PMID- 17853039 TI - Radio-frequency ablation: new technology for palliative treatment of hematuria in disseminated renal cell carcinoma. AB - Hematuria is often a significant symptom in patients with disseminated renal cell carcinoma. We present a case in which the minimally invasive procedure of radio frequency ablation was used in a patient with serious hematuria. The procedure was completely successful and there were no complications. In our opinion it may be recommended in such a situation. PMID- 17853041 TI - Effect of hemodialysis on serum complexed prostate-specific antigen levels. AB - OBJECTIVE: The measurement of prostate-specific antigen (PSA) is a useful tool in the screening and follow-up of prostate cancer, but its diagnostic validity is uncertain in hemodialysis patients. The aim of this study was to evaluate the effects of hemodialysis on serum complexed PSA (cPSA) levels. MATERIAL AND METHODS: A total of 36 men (mean age 62.54+/-8.20 years) with end-stage renal disease were enrolled in a prospective study. Serum total PSA (tPSA), free PSA (fPSA) and cPSA, and hematocrit levels were measured before and immediately after dialysis using low-flux membranes in the serum and in the dialysis ultrafiltrate. RESULTS: After hemodialysis, cPSA, fPSA and the fPSA:tPSA ratio increased significantly (p<0.05). However, there was no significant increase in tPSA. fPSA, cPSA and tPSA were not detected in ultrafiltrate. Hematocrit levels increased significantly (p<0.0001) due to hemoconcentration. Of patients with initial serum tPSA and cPSA values and fPSA:tPSA ratios below the cut-off values, none had a post-hemodialysis value greater than the cut-off point. There were weak correlation between the difference in values after and before hemodialysis of hematocrit and cPSA (p=0.035), and between the percentage change in levels before and after hemodialysis of hematocrit and cPSA (p=0.041). CONCLUSIONS: Hemodialysis induced elevations in all forms of PSA, but tPSA was the least affected form. cPSA did not show any diagnostic superiority over other forms of PSA. Thus, serum tPSA remains a reliable parameter for follow-up of prostate cancer in uremic patients receiving long-term dialysis. However, further research is needed to explain the pathophysiology of alterations in the concentrations of different forms of PSA. PMID- 17853040 TI - Short-term efficacy and long-term compliance/treatment failure of the alpha1 blocker naftopidil for patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. AB - OBJECTIVE: To evaluate treatment failure during a 4-year follow-up period after administration of naftopidil for patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) in real-life clinical practice. MATERIAL AND METHODS: A total of 247 patients with LUTS/BPH who had an International Prostate Symptom Score (IPSS) of > or =8 were enrolled in the study. Naftopidil, 50 mg/day, was given to the patients. They were followed for 4 years with periodic evaluation. Treatment failure was defined as conversion to other medical treatment or to surgery. RESULTS: Of the 247 patients, treatment failure occurred in 42 (17.0%) during the 4-year follow-up period. The 4-year treatment failure rate was on the Kaplan-Meier curve 35.0%. Among parameters assessed at baseline, prostate volume (PV) was the only significant determinant of treatment failure: patients with a PV of > or =35 ml had a 2.1 times higher hazard of treatment failure than those with a PV of <35 ml (95% CI 1.06-4.33; p=0.03). Patients with a severe IPSS at 12 weeks after administration of naftopidil had a 3.5 times higher hazard than those having a mild/moderate IPSS (95% CI 1.34-9.26; p=0.01). After 4 years, 200 patients (81%) had stopped taking naftopidil because of adverse events, treatment failure, loss to follow-up, etc. CONCLUSIONS: There were significant improvements in IPSS and urinary flow rate with naftopidil although it is unknown whether these improvements were significantly larger than the placebo effect as the study was non-randomized. However, only 19% of patients were known to have continued with the same medication for 4 years in real-life clinical practice. Patients who have a large prostate at baseline and a severe IPSS at 12 weeks after treatment are more likely to have treatment failure, although a prospective study is needed to confirm this. PMID- 17853043 TI - Role of eicosanoids of the contralateral kidney in maintenance of two-kidney, one clip renovascular hypertension in rats. AB - OBJECTIVE: To elucidate the role of the eicosanoids prostaglandin E(2) (PGE(2)), 6-keto-prostaglandin F(1a) (PGF(1a)) and thromboxane B(2) (TXB(2)) in the maintenance of two-kidney, one-clip renovascular hypertension in rats. MATERIAL AND METHODS: The right renal artery was constricted by a silver clip in 63 male Sprague-Dawley rats to induce hypertension, while a sham operation was performed in 17 control rats. Six months after the induction of hypertension, nephrectomy of the clipped kidney was performed. Nephrectomy was followed by a period of high sodium intake. Blood pressure and eicosanoid excretion were measured before and after nephrectomy of the clipped kidney, as well as during high sodium intake. RESULTS: During the chronic phase of Goldblatt hypertension, the amount of vasoconstrictive TXB(2) excreted by the contralateral kidney increased compared to that in the controls, whereas PGE(2) excretion was unaffected. Eicosanoid excretion before and after removal of the clipped kidney did not differ between post-Goldblatt hypertensive and post-Goldblatt normotensive animals. During the period of high sodium intake, PGE(2) excretion increased only in control rats, being unaltered in Goldblatt hypertensive rats. CONCLUSIONS: In the chronic phase of two-kidney, one-clip renovascular hypertension, the contralateral kidney of post-Goldblatt hypertensive and post-Goldblatt normotensive rats excretes more vasoconstrictive thromboxane in comparison to controls, whereas excretion of vasodilatory prostaglandin is not elevated. However, increased TXB(2) excretion and the absence of an increase in PGE(2) excretion from the contralateral kidney do not appear to be important for the maintenance of high blood pressure in this model of renovascular hypertension. PMID- 17853044 TI - Mycophenolate mofetil treatment of crescentic Henoch-Schonlein nephritis with IgA depositions. AB - Mycophenolate mofetil (MMF) is considered to be a promising therapeutic agent in primary glomerulonephritis but there are no data on the use of MMF in Henoch Schonlein nephritis (HSN). Herein we report the first adult crescentic HSN patient in whom long-term complete remission was achieved after MMF therapy. PMID- 17853045 TI - Economic impact of tension-free vaginal tape surgery for urinary incontinence in an ambulatory regimen compared with hospital admission: a study of the minimization of costs of a public hospital in Spain. AB - OBJECTIVES: To determine the cost per patient of a tension-free vaginal tape procedure involving major ambulatory surgery (MAS) compared with inpatient surgery in 2002 and 2003, and to analyse the medical care given following each procedure in a public hospital in Spain. MATERIAL AND METHODS: The method used was activity-based costing, which involves designing a protocol of processes of caring for the patient with the help of professionals and subsequently calculating the cost of each process; this system was applied retrospectively to patients cared for in 2002 and 2003. In addition, the clinical histories of these patients were reviewed in order to evaluate complementary care given by the emergency service and admissions to hospital immediately following surgery. The relation between these events and each sample group was analysed by means of a non-parametric test and CIs for a 95% level of significance were obtained in order to make the calculations more robust. RESULTS: The mean cost for the patients in the ambulatory group was 42.43% lower than that for the hospitalized patients. Whereas 5.5% of the ambulatory patients subsequently required admission and a further 7.3% required complementary medical care, 19.2% of the patients who had been hospitalized for the surgery required complementary medical care and 1.4% were readmitted after intervention. In spite of these results, there was no dependence between these variables according to the chi(2) test. CONCLUSION: MAS produced better results in terms of minimizing costs; under our conditions it was less costly but was of equal efficacy to the surgical intervention. PMID- 17853046 TI - Tissue microarrays from renal cell tumors: exclusion criteria and rate of exclusion. AB - OBJECTIVES: Exclusion of tissue microarray (TMA) cores can cause the total loss of a tumor case, and this can have a potentially negative effect on the results of TMA-based studies. The main aim of this study was to evaluate the loss of informative cores having cut a given number of slices from a TMA block. A further objective was to investigate the effect in various subtypes of renal cell tumors and the detailed reasons for the loss of informative cores. MATERIAL AND METHODS: A TMA was constructed from renal tumor specimens (n=461). The cause and rate of exclusion were evaluated in the first slice (FS) and last slice (LS) (i.e. the 40th) cut from the TMA blocks. Furthermore, the overall case loss under the assumptions that only one, two or three cores per case were punched was extrapolated. RESULTS: Sarcomatoid and papillary renal cell carcinomas showed the highest overall exclusion rate. Irrespective of the type of tumor, however, the case loss was approximately tripled from FS to LS. Furthermore, extrapolation showed that a reduction in the number of cores punched per case, for example by one, would further double the number of cases lost. Reasons for exclusion were mainly as follows: core loss; <25% tumorous tissue per core; core folding; and core with necrotic area. CONCLUSION: This study shows that punching at least three to four cores per case is advisable when constructing TMAs from oncocytoma and renal cell carcinoma specimens, and that the type of tumor has an effect on the cause and rate of core exclusion. PMID- 17853047 TI - Irrigation with isoproterenol diminishes increases in pelvic pressure without side-effects during ureterorenoscopy: a randomized controlled study in a porcine model. AB - OBJECTIVE: Recently, we showed that endoluminally administered isoproterenol (ISO) inhibits muscle function of the pyeloureter in swine. This may be of value in managing increases in pelvic pressure during upper urinary tract endoscopy. The purpose of this study was to examine the effect of endoluminally administered ISO on increases in pelvic pressure and cardiovascular function during flexible ureterorenoscopy. MATERIAL AND METHODS: The study was performed in anaesthetized female pigs. In terms of endoscopic procedures, the pigs were randomized as follows: Group 1, irrigation with 0.1 microg/ml ISO added to saline (n=12); and Group 2, irrigation with saline (n=10). A 5-Fr catheter was retrogradely placed in the renal pelvis and an 8-Fr catheter in the bladder for pressure measurements. Flexible ureterorenoscopy was performed with constant irrigation at a perfusion rate of 8 ml/min. Pelvic, bladder and blood pressure and heart rate were registered continuously. RESULTS: Mean baseline pelvic pressure was identical in both groups: 12+/-2.3 mmHg in Group 1 and 14+/-3.6 mmHg in Group 2 (p=0.26). During ureterorenoscopy, mean pelvic pressure increased to 26+/-2.3 mmHg in Group 1 and to 38+/-3.1 mmHg in Group 2. Hence ISO reduced the pressure increase due to ureterorenoscopy by 42% (p<0.001). Pelvic pressure seemed to be independent of bladder pressure, which showed no difference between the two groups (p=0.067). Blood pressure and heart rate showed no significant differences between the two groups: p=0.425 and p=0.166, respectively. CONCLUSIONS: ISO (0.1 microg/ml) added to irrigation fluid significantly reduces the increase in pelvic pressure during ureterorenoscopy in pigs, without concomitant side-effects. PMID- 17853048 TI - Spontaneous cutaneous ulcers in a patient with a moderate degree of chronic kidney disease: a different spectrum of calciphylaxis. AB - Calciphylaxis is characterized by the development of spontaneous skin ulcers that often progress to deep tissue necrosis. We present a case of calciphylaxis in a patient with chronic kidney disease (CKD) prior to the initiation of dialysis. We conclude that calciphylaxis should be considered in the differential diagnosis of skin ulcerations in patients with any degree of CKD. PMID- 17853049 TI - Photodynamic therapy with methyl aminolevulinate for atypial carcinoma in situ of the penis. AB - OBJECTIVE: Photodynamic therapy (PDT) has been investigated as an alternative treatment for cutaneous squamous cell carcinoma in situ (CIS), also known as Bowen's disease. Atypia of the squamous epithelium is graded, with the most severe atypia being equivalent to CIS. CIS on the penis is regarded as a premalignant condition and is seen either in isolation or in conjunction with carcinoma of the penis. MATERIAL AND METHODS: A group of 10 patients with atypia/CIS were treated with PDT between December 2002 and April 2005. The group consisted of five patients with primary lesions and five with atypia after an organ-preserving operation for carcinoma of the penis. RESULTS: Eight patients were treated once, one twice and one six times. When complete remission was not achieved, a biopsy was taken for diagnosis. Three of the 10 patients had histopathological residual disease after a median follow-up period of 20 months (range 15-36 months). The first week after treatment could be painful but the cosmetic results were excellent. There was almost no loss of substance or fibrosis in the treated area, and sensitivity was restored to normal after approximately 1 month. CONCLUSIONS: In our experience, PDT for CIS seems to be a promising treatment modality with regard to cancer control, organ preservation, cosmetics and functional results. As with laser therapy of these lesions, careful follow-up is mandatory. Larger studies are needed and are planned. PMID- 17853050 TI - Successful disc surgery after 17 years of erectile dysfunction caused by a "silent" disc protrusion. AB - A 35-year-old male with normal erectile function up until the age of 18 years subsequently suffered permanent erectile dysfunction for the next 17 years. At the age of 15 years he had fallen from a horse and landed on his buttocks. He also complained of slight voiding dysfunction. Uroflowmetry showed reduced flow, indicating a possible common neurogenic cause of the disturbed bladder function and erectile dysfunction. CT of the lumbar spine showed a large protrusion of the intervertebral disc L5-S1. After operative removal of the protrusion, a normal erection was achieved after 15 days and urine flow improved at 1 and 2 months and became normal after 3 months. Both erectile and bladder function continued to be normal 10 years later. Thus, the effects of long-lasting mechanical compression of parasympathetic nerves need not be irreversible. Uroflowmetry is also a test for neurogenic aetiology of erectile dysfunction, as bladder contractility and erection are both dependent upon parasympathetic innervation from the spinal segments S2-S4. PMID- 17853051 TI - Recurrence of light-chain deposition disease after renal transplantation. AB - A 51-year-old male with a history of chronic renal disease received a renal allograft, in which disease recurred. Light-chain deposition disease was confirmed through biopsies of the native kidney and graft, and detection of free kappa light chains in serum. PMID- 17853052 TI - Artificial neural networks for assessing the risk factors for urinary calcium stones according to gender and family history of stone. AB - OBJECTIVE: In a previous work, we evidenced that artificial neural networks (ANNs) were more informative than classical statistical analyses for assessing the risk of idiopathic calcium nephrolithiasis in male stone-formers. MATERIAL AND METHODS: We compared risk factors for idiopathic calcium nephrolithiasis (age, body mass index, calcemia, calcium oxalate supersaturation, and 24-h calciuria, oxaluria, uricosuria, citraturia, urea, and sodium) in four populations: men and women with and without a family history of stone (FHS). A total of 119 males (58 with an FHS, 61 without) and 59 females (30 with an FHS, 29 without) were compared to healthy controls. For each variable, receiver operating characteristic (ROC) curve indices were calculated by means of ANNs. RESULTS: In men without an FHS, the most discriminant variables were 24-h urea (ROC curve index 0.76), supersaturation (ROC curve index 0.72), 24-h calciuria (ROC curve index 0.68), 24-h uricosuria (ROC curve index 0.64), 24-h oxaluria (ROC curve index 0.63), 24-h sodium (ROC curve index 0.62), and calcemia (ROC curve index 0.60). In men with an FHS, only supersaturation (ROC curve index 0.67) was discriminant. In women without FHS, calcemia (ROC curve index 0.67), 24 h calciuria (ROC curve index 0.64), and 24-h uricosuria (ROC curve index 0.62) were discriminant. In women with an FHS, supersaturation (ROC curve index 0.70), 24-h uricosuria (ROC curve index 0.69), 24-h urea (ROC curve index 0.68), and 24 h calciuria (ROC curve index 0.67) were discriminant. CONCLUSIONS: Risk factors for idiopathic calcium nephrolithiasis were roughly the same in men with or without an FHS, and in women with an FHS. In these patients, calcium oxalate supersaturation and 24-h urea were the most discriminant factors. Conversely, in women without an FHS, calcium abnormalities (calcemia, 24-h calciuria) were discriminant and should prompt a search for infraclinical primary hyperparathyroidism or sarcoidosis. PMID- 17853054 TI - Organization of cortical processing for facial movements during licking in cats. AB - We proposed that cortical organization for the execution of adequate licking in cats was processed under the control of two kinds of affiliated groups for face and jaw & tongue movements (Hiraba H, Sato T. 2005A. Cerebral control of face, jaw, and tongue movements in awake cats: Changes in regional cerebral blood flow during lateral feeding Somatosens Mot Res 22:307-317). We assumed the cortical organization for face movements from changes in MRN (mastication-related neuron) activities recorded at area M (motor cortex) and orofacial behaviors after the lesion in the facial SI (facial region in the primary somatosensory cortex). Although we showed the relationship between facial SI (area 3b) and area M (area 4delta), the property of area C (area 3a) was not fully described. The aim of this present study is to investigate the functional role of area C (the anterior part of the coronal sulcus) that transfers somatosensory information in facial SI to area M, as shown in a previous paper (Hiraba H. 2004. The function of sensory information from the first somatosensory cortex for facial movements during ingestion in cats Somatosens Mot Res 21:87-97). We examined the properties of MRNs in area C and changes in orofacial behaviors after the area C or area M lesion. MRNs in area C had in common RFs in the lingual, perioral, and mandibular parts, and activity patterns of MRNs showed both post- and pre-movement types. Furthermore, cats with the area C lesion showed similar disorders to cats with the area M lesion, such as the dropping of food from the contralateral mouth, prolongation of the period of ingestion and mastication, and so on. From these results, we believe firmly the organization of unilateral cortical processing in facial SI, area C, and area M for face movements during licking. PMID- 17853055 TI - Cortical and spinal control of ankle joint muscles before and during gait initiation. AB - The purpose of this study was to investigate control of the ankle joint muscles before and during gait initiation. Seven healthy humans, aged 20-30 years old, participated in this study. Motor-evoked potentials (MEPs) were recorded from the soleus and the tibialis anterior muscles, and H-reflexes were evoked from the soleus muscle in the stance leg of gait initiation. The soleus H-reflexes were depressed throughout all the periods before and during gait initiation. The soleus MEP amplitudes were decreased in some periods before gait initiation, but were increased in other periods before and during gait initiation. The MEP amplitudes in the tibialis anterior muscle were increased before the onset of the EMG activity, and this increase persisted through gait initiation. The findings indicate that the ankle joint flexor is under intensive cortico-spinal control before and during gait initiation. Both the cortical and spinal pathways are involved in preparing and controlling the activity of the ankle joint extensor for gait initiation. PMID- 17853056 TI - Tactile spatial resolution measured manually: a validation study. AB - The purpose of this study was to investigate the validity of manual application of the grating orientation task (GOT), as currently used in fundamental and clinical research. Six examiners tested 12 subjects following recommendations of the literature. The results show that the normal force applied with the domes on the skin varied from one examiner to the next. Nevertheless, it did not affect the performance of the subjects, whose thresholds were consistent with those reported in the literature. This study highlights the inter-examiner reliability in the manual application of this test and validates this procedure. PMID- 17853057 TI - Barrels XIX Meeting report. PMID- 17853058 TI - Motor cortex neuroplasticity associated with lingual nerve injury in rats. AB - The aim of this study was to determine if lingual nerve trauma affects the features of face primary motor cortex (MI) defined by intracortical microstimulation (ICMS). The left lingual nerve was transected in adult male rats by an oral surgical procedure; sham rats (oral surgery but no nerve transection) as well as naive intact rats served as control groups. ICMS was applied at post operative days 0, 7, 14, 21, and 28 to map the jaw and tongue motor representations in face MI by analyzing ICMS-evoked movements and electromyographic activity recorded in the genioglossus (GG) and anterior digastric (AD) muscles. There were no statistically significant effects of acute (day 0) nerve transection or sham procedure (p > 0.05). The surgery in the sham animals was associated with limited post-operative change; this was reflected in a significant (p < 0.05) increase in the number of GG sites in left MI at post operative day 14 compared to day 0. However, nerve transection was associated with significant increases in the total number of AD and GG sites in left or right MI or specifically the number of GG sites in rats at post-operative days 21 or 28 compared to earlier time periods. There were also significant differences between nerve-transected and sham groups at post-operative days 7, 14, or 21. These findings suggest that lingual nerve transection is associated with significant time-dependent neuroplastic changes in the tongue motor representations in face MI. PMID- 17853059 TI - Measurement and meaning of salivary cortisol: a focus on health and disease in children. AB - Measurement of salivary cortisol can provide important information about hypothalamic-pituitary-adrenal (HPA) axis activity under normal conditions and in response to stress. However, there are many variables relating to the measurement of cortisol in saliva which may introduce error and therefore may render difficult the comparison and interpretation of data between, and within, laboratories. This review addresses the effects of gender, age, time and location of sampling, units of measurement, assay conditions and compliance with the protocol, all of which have the potential to impact upon the precision, accuracy and reliability of salivary cortisol measurements in the literature. Some of these factors are applicable to both adults and children, but the measurement of salivary cortisol in children introduces aspects of unique variability which demand special attention. The specific focus of this review is upon the somewhat neglected area of methodological variability of salivary cortisol measurement in children. In addition to these methodological issues, the review highlights the use of salivary cortisol measurements to provide information about HPA axis dysfunction associated with psycho- and patho-physiological conditions in children. Novel applications for salivary cortisol measurements in future research into HPA axis activity in children are also discussed. PMID- 17853060 TI - The effect of adrenalectomy on Fos expression in vasopressinergic and oxytocinergic neurons in response to stress in the rat. AB - This study evaluated the responses of vasopressin (AVP) and oxytocin (OT) neurons to alterations in hypothalamo-pituitary axis activity by adrenalectomy (ADX) or after restraint stress compared with basal conditions. Wistar male rats were perfuse-fixed by cardiac perfusion under anesthesia 3 h, 1, 3 and 14 days after ADX or Sham surgery. Coronal hypothalamic sections were used for evaluation of Fos, AVP and OT expression by immunohistochemistry. Under basal conditions and after stress, Fos-AVP double labeling showed no difference in the magnocellular subdivisions of the paraventricular nuclei (PVN) or in the supraoptic nuclei (SON), suggesting that the magnocellular AVP system is unlikely to contribute to ACTH secretion after restraint in both Sham and ADX rats. Fos-AVP double labeling in the parvocellular medial paraventricular nucleus (PaMP) in ADX groups was increased after 3 h in basal conditions, and in all periods after restraint stress. There were no differences between Sham and ADX groups in Fos-OT double labeling in any subdivision of the PVN; however, in the SON, the number of Fos-OT double labeled cells was increased at all time-points after stress in the ADX group. Fos expression was increased in the PaMP after 3 h and after restraint stress in the Sham and ADX groups, especially in the ADX group. In conclusion, Fos expression in different cell populations of the PVN can be differentially regulated by short- and long-term absence of glucocorticoid negative feedback and also by stress-related excitatory and/or inhibitory neural inputs. The Fos-AVP double labeling findings in the PaMP also indicate a minor participation of these vasopressinergic neurons in the regulation of the HPA axis after ADX. PMID- 17853061 TI - Chronic administration of an angiotensin II receptor antagonist resets the hypothalamic-pituitary-adrenal (HPA) axis and improves the affect of patients with diabetes mellitus type 2: preliminary results. AB - Diabetes mellitus type 2 (DM type 2) is associated with depressive symptomatology and intermittent hyperfunction of the hypothalamic-pituitary-adrenal (HPA) axis. DM type 2 is also accompanied by increased tissue levels of angiotensin II (Ang II), which stimulates the HPA axis through the Ang II type 1 receptors (AT1). We investigated the effect of candesartan, an angiotensin receptor blocker (ARB) that crosses the blood brain barrier, on the activity of the HPA axis and on the affect of 17 patients with DM type 2, aged 40-65 years, who were treated with 4 mg/day candesartan per os for at least 3 months. Before and after candesartan administration, a corticotropin-releasing hormone (CRH) stimulation test and psychological tests were performed. In response to hCRH, time-integrated secretion of ACTH was not altered by candesartan administration, however, the cortisol response was decreased significantly compared to baseline (mean +/- SEM, 2327 +/- 148.3 vs. 1943 +/- 131.9 microg/dl, P = 0.005) suggesting reduced sensitivity of the adrenals to ACTH. In parallel, there was a significant improvement in interpersonal sensitivity (0.91 +/- 0.16 vs. 0.70 +/- 0.15, P = 0.027) and depression scores (0.96 +/- 0.15 vs. 0.71 +/- 0.10, P = 0.026). We suggest that candesartan resets the HPA axis of patients with DM type 2 and improves their affect. PMID- 17853062 TI - Mid-life stress is associated with both up- and down-regulation of markers of humoral and cellular immunity. AB - Perception of stress with consequent activation of a neuroendocrine cascade causes changes in immune function that may be bi-directional, with alterations in basal levels of biological parameters outside the optimal range. In this cross sectional study of 302 healthy persons (males 56.3%, females 43.7%) aged 41-46 years, higher stress levels, as assessed by questionnaire measures of recurrent and recent perceived stress, were associated with a 4-fold greater risk of having a high compared to mid-range serum neopterin concentration, indicating activation of cellular immune mechanisms [adjusted odds ratio, OR; (95% confidence intervals, CI): Low stress=1.00 (reference group); Medium stress=4.13 (1.51, 11.29); High stress=4.63, (1.35, 15.83), p for trend=0.01]. Higher stress levels were associated with a 3-fold greater risk of having signs of humoral immune activation, as indicated by salivary IgA concentration [high compared to mid range salivary IgA: Low stress=1.00 (reference group); Medium stress=1.06 (0.48, 2.34); High stress=3.62 (1.26, 10.39), p for trend=0.02], but also a 4-fold greater risk of humoral immune depression [low compared to mid-range IgA: Low stress=1.00 (reference group); Medium stress=1.72 (0.74, 3.99); High stress=4.38 (1.47, 13.00), p for trend=0.02]. In conclusion, in this cross-sectional study, higher stress levels were associated with higher serum neopterin and both elevated and depressed salivary IgA levels. These findings emphasise the importance of considering that stress may have bi-directional effects on immune mechanisms, and are consistent with an activational effect of chronic, perceived stress on cellular immunity, and a bi-directional effect on IgA levels, one aspect of humoral immunity. PMID- 17853063 TI - Tumor necrosis factor-associated protein 1 (TRAP-1) protects cells from oxidative stress and apoptosis. AB - TRAP-1 is a mitochondrial heat shock protein (HSP), recently identified in Saos-2 osteosarcoma cells adapted to mild oxidative stress induced by diethylmaleate (DEM). TRAP-1 mRNA expression is increased in DEM-adapted cells as well as in tumor cells resistant to 5-fluorouracil and to platin derivatives. Since a strong decrease of TRAP-1 protein levels, upon cisplatin treatment, is observed only in controls but not in the DEM-adapted counterpart, a possible role for this protein in the development of resistant phenotypes could be hypothesized. To characterize the protective role of TRAP-1 against oxidative stress and apoptosis, stable transfectants were generated and characterized for their response to different stress types. These stable clones expressing constitutively high TRAP-1 levels: (i) are more resistant to H2O2-induced DNA damage and to apoptosis by cisplatin; (ii) contain higher reduced glutathione (GSH) levels than control cells; and (iii) do not release the apoptosis-inducing factor into the nucleus upon cisplatin treatment. Furthermore, high TRAP-1 levels interfere with caspase 3 activation. These results confirm the anti-apoptotic role of TRAP-1, and suggest that increased expression of this mitochondrial HSP in DEM-adapted and chemoresistant cells could be part of a pro-survival signaling pathway aimed to evade toxic effects of oxidants and anticancer drugs. PMID- 17853064 TI - Negative affect as a predisposing factor for cortisol release after an acute stress--the impact of unpleasant priming. AB - Glucocorticoids have a key role in stress responses. There are, however, substantial differences in cortisol reactivity among individuals. We investigated if affective trait and mood induction influence the reactivity to psychological stress in a group of 63 young adults, male (n=27) and female (n=36), aged ca. 21 years. On the experimental day the participants viewed either a block of pleasant or unpleasant pictures for 5 min to induce positive or negative mood, respectively. Then, they had 5 min to prepare a speech to be delivered in front of a video-camera. Saliva samples were collected to measure cortisol, and questionnaire-based affective scales were used to estimate emotional states and traits. Compared to basal levels, a cortisol response to the acute speech stressor was only seen for those who had first viewed unpleasant pictures and scored above the average on the negative affect scale. There were no sex differences. In conclusion, high negative affect associated with exposure to an unpleasant context increased sensitivity to an acute stressor, and was critical to stimulation of cortisol release by the speech stressor. PMID- 17853065 TI - Resilience and vagal tone predict cardiac recovery from acute social stress. AB - Previous studies showed that heart period decreases during and recovers after an acute stress. We investigated if individual predispositions and emotional priming influence heart period recovery after a speech stress task. Psychometric scales and resting cardiac vagal tone were used to measure individual traits. The presentation of a sequence of either pleasant or unpleasant pictures, as emotional primers, preceded the speech stress. Heart period was measured throughout the experiment. Stress induced tachycardia irrespective of emotional priming or traits. In the recovery period, participants with higher resting cardiac vagal tone or presenting higher resilience significantly reduced the heart acceleration. Furthermore, these traits interacted synergistically in the promotion of the recovery of heart period. Pleasant priming also improved recovery for participants with lower negative affect. In conclusion, the stress recovery measured through heart period seemed dependent upon individual predispositions and emotional priming. These findings further strengthen previous observations on the association between greater cardiac vagal tone and the ability to regulate emotion. PMID- 17853066 TI - Neuroendocrine stress responses to an oral academic examination: No strong influence of sex, repeated participation and personality traits. AB - Public speaking tasks have been widely used as laboratory stressors in human research. Fewer studies have investigated similar real life situations like oral examinations and results have been inconsistent. The present study investigated salivary cortisol (as a marker of hypothalamus-pituitary-adrenal (HPA) activity) and salivary alpha-amylase (sAA as a marker of sympathetic nervous system (SNS) activity) within the context of a university examination. Subjects were 40 undergraduate students who participated in an oral examination. Of these, 20 also participated in a second examination within a few weeks. Cortisol and sAA were measured immediately before and after the examination and on a control day. Additionally, subjects filled out personality questionnaires. A strong anticipatory increase in salivary cortisol and sAA as well as more modest further increases between the pre- and post-measurements were detected during the examination. Sex or oral contraceptive use had no influence on either measure. In addition, no significant differences between the first and second examination were observed. The findings indicate the neuroendocrine stress responses to laboratory stressors and to heralded real life stressors as well as the modulatory variables involved differ from each other. PMID- 17853067 TI - HPA axis and sleep: identifying subtypes of major depression. AB - It is increasingly acknowledged that the diagnosis of major depression encompasses patients who do not necessarily share the same disease biology. Though the diagnostic criteria allow the specification of different subtypes, e.g. melancholic and atypical features, a consensus still has to be reached with regard to the clinical symptoms that clearly delineate these subtypes. Beside clinical characteristics, biological markers may help to further improve identification of biologically distinct endophenotypes and, ultimately, to devise more specific treatment strategies. Alterations of the hypothalamus-pituitary adrenal (HPA) axis and sleep architecture are not only commonly observed in patients with major depression, but the nature and extent of these alterations can help to identify distinct subtypes. Thus, a HPA overdrive, due to enhanced secretion of corticotropin-releasing hormone (CRH) and an impaired negative feedback via glucocorticoid receptors, seems to be most consistently observed in patients with melancholic features. These patients also show the clearest sleep electroencephalogram (EEG) alterations, including disrupted sleep, low amounts of slow wave sleep (SWS), a short rapid eye movement (REM) latency and a high REM density. In contrast, patients with atypical features are characterized by reduced activity of the HPA axis and ascending noradrenergic neurons in the locus coeruleus. Though sleep-EEG alterations have been less thoroughly examined in these patients, there are data to suggest that SWS is not reduced and that REM sleep parameters are not consistently altered. While the atypical and melancholic subtypes of major depression may represent the extremes of a spectrum, the distinct clinical features provide an opportunity to further explore biological markers, as well as environmental factors, contributing to these clinical phenotypes. Moreover, dysregulations of the HPA axis and sleep-EEG alterations can also be induced in rodents, thereby allowing alignment of critical biological aspects of a human disease subtype with an animal model. Such "Translational Research" efforts should help to develop targeted therapies for distinct patient populations. PMID- 17853068 TI - Water temperature determines neurochemical and behavioural responses to forced swim stress: an in vivo microdialysis and biotelemetry study in rats. AB - Forced swimming is a behavioural stress model increasingly used to investigate the neurocircuitry of stress responses. Although forced swim stress clearly is a psychological stressor (anxiety, panic), its physical aspects are often neglected. There are indications that behavioural and neurochemical responses to swim stress depend on the water temperature. Thus, we investigated the responsiveness of hippocampal serotonergic neurotransmission (important in the coordination of stress responses), and of behaviour and core body temperature to forced swimming at different water temperatures (19, 25 and 35 degrees C). In vivo microdialysis and biotelemetry in freely-behaving rats were used. Dialysates were analysed for serotonin (5-HT) and its metabolite 5-HIAA (5 hydroxyindoleacetic acid) by HPLC with electrochemical detection. Forced swimming in water at 25 and 19 degrees C decreased core body temperature by 8 and 12 degrees C, respectively. A rapid and pronounced increase in hippocampal 5-HT and 5-HIAA was found in rats that swam at 35 degrees C, whereas biphasic responses in 5-HT and 5-HIAA were observed at 25 and 19 degrees C. Also swim stress behaviour and post-stress home cage behaviour depended on the water temperature. Comparing the serotonergic and core body temperature changes revealed that a combination of two different 5-HT and 5-HIAA responses seems to shape the neurotransmitter response. Swimming-induced increases in hippocampal extracellular concentrations of 5-HT and 5-HIAA occurred at all water temperatures, but these increases were temporarily quenched, or concentrations were transistently decreased, when core body temperature fell below 31 degrees C in water at 25 or 19 degrees C. These data demonstrate that water temperature is a key factor determining the impact of forced swim stress on behaviour and neurochemistry, and underscore that changes in these parameters should be interpreted in the light of the autonomic responses induced by this stressor. PMID- 17853069 TI - Neuronal nitric oxide synthase gene inactivation reduces the expression of vasopressin in the hypothalamic paraventricular nucleus and of catecholamine biosynthetic enzymes in the adrenal gland of the mouse. AB - The impact of a lifelong absence of the neuronal nitric oxide synthase (nNOS) in the neuroendocrine stress response was investigated in nNOS knockout (KO) and wild type (WT) mice under basal conditions and in response to forced swimming. In the hypothalamic paraventricular nucleus oxytocin and corticotropin-releasing hormone mRNA levels did not differ between these genotypes under resting conditions, whereas vasopressin mRNA levels were significantly lower in nNOS KO than in WT animals. Also, in the adrenal glands basal levels of tyrosine hydroxylase protein, the rate-limiting enzyme for catecholamine biosynthesis, and of phenylethanolamine N-methyltransferase, which converts norepinephrine to epinephrine, were significantly reduced in nNOS KO mice. Plasma adrenocorticotropin, corticosterone, norepinephrine and epinephrine levels were similar in the KO and WT genotypes under resting conditions. In response to forced swimming, a similar increase in plasma adrenocorticotropin and corticosterone was observed in KO and WT animals. Stressor exposure triggered also an increased epinephrine release in WT animals, but did not significantly alter plasma epinephrine levels in KO mice. These data suggest that the chronic absence of nNOS reduces the capacity of epinephrine synthesising enzymes in the adrenal gland to respond to acute stressor exposure with an adequate epinephrine release. PMID- 17853070 TI - Anticipation of subsequent demanding exercise increases the expression of haem oxygenase-1 mRNA in human lymphocytes. AB - Oxidative stress induces the expression of the cytoprotective and anti inflammatory protein haem oxygenase-1 (HO-1). In the present investigation, we show that anticipation of subsequent exercise elevates the expression of HO-1 mRNA in lymphocytes. A between-groups comparison of HO-1 mRNA expression in subjects about to complete a half marathon race vs. subjects who were asked to sit quietly in the laboratory showed an elevated expression of HO-1 mRNA prior to exercise (2.6-fold higher in subjects prior to the half marathon, P < 0.01). This observation led us to examine whether anticipation of subsequent exercise leads to differences in lymphocyte HO-1 mRNA expression within the same subjects. In a second experiment, the same individuals completed two trials, one exercise and one rest, approximately 2 weeks apart in a randomised cross-over design. Lymphocyte HO-1 mRNA expression was greater prior to exercise (1.4 +/- 0.3-fold higher in the exercise trial, P < 0.05). These results suggest that knowledge of subsequent demanding exercise may lead to an anticipatory induction of HO-1 mRNA. We tentatively propose that this process has evolved to prepare lymphocytes for subsequent exercise-induced oxidative stress although the mechanism remains to be elucidated. PMID- 17853071 TI - Examination stress and components of working memory. AB - Previous research suggests that stress can influence a broad range of memory functions. In this study we investigated the effect of a naturalistic stressor, examination stress, on working memory in young adults. In order to accomplish this aim, participants were tested on psychological and hormonal measures of stress and on Digit Span, once during a low stress period and once during a high stress period. The high examination stress condition was associated with an increase in cortisol and subjective impressions of stress. Although Digits Forward performance did not vary with examination stress, Digits Backward performance improved. These findings suggest that mild increases in stress are associated with improvement in the manipulation component of working memory. However, no correlations were found between working memory and either cortisol or psychological stress. Thus the mechanism by which mild naturalistic stressors improve the manipulation component of working memory needs further investigation. PMID- 17853072 TI - Acute stress or systemic insulin injection increases flunitrazepam sensitive GABAA receptor density in synaptosomes of chick forebrain: Modulation by systemic epinephrine. AB - Interactions between acute stress and systemic insulin and epinephrine on GABAA receptor density in the forebrain were studied. Here, 10 day-old chicks were intraperitoneally injected with insulin, epinephrine or vehicle and then immediately stressed by partial water immersion for 15 min and killed by decapitation. Non-stressed controls were similarly injected, then returned to their rearing boxes for 15 min and then killed. Forebrains were dissected and GABAA receptor density was measured ex vivo in synaptosomes by 3[H]-flunitrazepam binding assay. In non-stressed chicks, insulin at 1.25, 2.50 and 5.00 IU/kg of body weight (non-hypoglycemic doses) increased Bmax by 33, 53 and 44% compared to saline, respectively. A similar increase of 41% was observed in receptor density after stress. However, the insulin effect was not additive to the stress-induced increase suggesting that both effects occur through similar mechanisms. In contrast, epinephrine, at 0.25 and 0.5 mg/kg did not induce any changes in Bmax in non-stressed chicks. Nevertheless, after stress these doses increased the receptor density by about 13 and 27%, respectively. Similarly, the same epinephrine doses co-administered with insulin (2.50 IU/kg), increased the receptor density by about 20% compared to insulin alone. These results suggest that systemic epinephrine, perhaps by evoking central norepinephrine release, modulates the increase in forebrain GABAA receptor binding induced by both insulin and stress. PMID- 17853073 TI - Chronic self-perceived stress and set-shifting performance in undergraduate students. AB - Given recent findings on the potential for detrimental effects of chronic stress on the prefrontal cortex, additional research on the relationship between chronic stress and performance on executive functioning tasks (dependent on prefrontal functioning) is needed. Eighty-one undergraduate students completed a self-report measure of stress over the previous month (perceived stress scale--PSS) and the comprehensive trail-making test (CTMT, Trials 3 and 5). Results revealed a statistically significant positive correlation between PSS score and time needed to complete Trial 5 of the CTMT, which places demands on the set-shifting component of executive functioning. This finding adds to a growing body of work that suggests a relationship between chronic stress and executive functioning, and extends these findings to include set-shifting performance. PMID- 17853074 TI - Influence of anabolic steroid on anxiety levels in sedentary male rats. AB - The aim of this study was to evaluate the influence of nandrolone decanoate on anxiety levels in rats. Male Wistar rats were treated with nandrolone decanoate (5mg/kg, two times per week, i.m.) or vehicle (propylene glycol--0.2 ml/kg, two times per week, IM) for 6 weeks. Control rats were subject only to procedures related to their routine husbandry. By the end of 6 weeks, all groups (24-29 rats/group) were submitted to the elevated plus maze test in order to evaluate their anxiety level. Some of these animals (12-14/group) were treated with diazepam (1 mg/kg i.p.) 30 min before the elevated plus maze test. Nandrolone decanoate significantly decreased the percentage of time spent in the open arms (1.46+/-0.49%) compared with control (3.80+/-0.97%) and vehicle (3.96+/-0.85%) groups, with no difference between control and vehicle treatments. The percentage of open arm entries was also reduced in the group treated with nandrolone decanoate in comparison with the vehicle and control. No changes in the number of closed arm entries were detected. Diazepam abolished the effects of nandrolone decanoate on the percentage of time in, and entries into the open arms. The present study showed that chronic treatment with a high dose of nandrolone decanoate increased the anxiety level in male rats. PMID- 17853075 TI - Memory consolidation during sleep: interactive effects of sleep stages and HPA regulation. AB - Sleep is critically involved in the consolidation of previously acquired memory traces. However, nocturnal sleep is not uniform but is subject to distinct changes in electrophysiological and neuroendocrine activity. Specifically, the first half of the night is dominated by slow wave sleep (SWS), whereas rapid eye movement (REM) sleep prevails in the second half. Concomitantly, hypothalamo pituitary-adrenal (HPA) activity as indicated by cortisol release is suppressed to a minimum during early sleep, while drastically increasing during late sleep. We have shown that the different sleep stages and the concomitant glucocorticoid release are interactively involved in the consolidation of different types of memories. SWS-rich early sleep has been demonstrated to benefit mainly the consolidation of hippocampus-dependent declarative memories (i.e. facts and episodes). In contrast, REM sleep-rich late sleep was shown to improve in particular emotional memories involving amygdalar function, as well as procedural memories (for skills) not depending on hippocampal or amygdalar function. Enhancing plasma glucocorticoid concentrations during SWS-rich early sleep counteracted hippocampus-dependent declarative memory consolidation, but did not affect hippocampus-independent procedural memory. Preventing the increase in cortisol during late REM sleep-rich sleep by administration of metyrapone impaired hippocampus-dependent declarative memory but enhanced amygdala-dependent emotional aspects of memory. The data underscore the importance of pituitary adrenal inhibition during early SWS-rich sleep for efficient consolidation of declarative memory. The increase in cortisol release during late REM sleep-rich sleep may counteract an overshooting consolidation of emotional memories. PMID- 17853076 TI - Age-related patterns of DHEAS among Turkana males of northern Kenya. AB - Dehydroepiandrosterone sulphate (DHEAS) has been widely associated with aging, but little is known about age-related decline of DHEAS in non-western populations. To determine the age-related pattern of DHEAS and its relationship to nutritional status in a subsistence population, we sampled Turkana nomads from northern Kenya. Subjects were 108 nomadic and 90 settled Turkana males, estimated ages 20 to 80+. Measures included blood DHEAS, height, weight, skinfolds, and waist circumference. Overall nomads exhibited less adiposity (5.7 +/- 1.8% versus 9.0 +/- 3.3% body fat) and higher blood DHEAS levels (5.2 +/- 3.3 microM versus 4.1 +/- 3.1 microM; p = 0.03). Age pattern of DHEAS was curvilinear, peaking in the 30s and 40s. General linear models (GLM) showed that blood DHEAS levels among men over 70 years of age were significantly lower than those in their 30s and 40s. Controlled for age, blood DHEAS was not related to adiposity. These results suggest that DHEAS levels were higher in those individuals who were calorie restricted. In addition, DHEAS levels rose more slowly than described in other populations, peaking in the fourth decade of life PMID- 17853077 TI - Speech and song: the role of the cerebellum. AB - An exploration into cerebellar activity during the perception and production of speech and song may elucidate general underlying cerebellar functions. Recently, the cerebellum has been hypothesized to be involved with sharpening sensory input, temporal coordination and processing of motor articulation and perception, as well as instantiation of internal models that simulate the input-output characteristics of a specific system. Sung language and spoken language share many common features (physiology for articulation and perception as well as phonology, phonotactics, syntax, and semantics of the underlying language), although they differ in certain vocal and prosodic aspects. A review of the literature on perception and production of singing and speech reveals considerable overlap in the lateral aspect of the VI lobule of the posterior cerebellum, a region known to somatotopically represent the lips and tongue. This region may instantiate internal models of vocal tract articulation that simulate well learned phonological and/or segmental articulatory - auditory/orosensory mappings utilized for both speech and singing. Recent results show tendencies for left cerebellar hemispheric specialization for processing of singing and right specialization for processing of speech, both in the VI lobule of the cerebellum, inferior to that found for representing both speech and singing. Given the crossed pattern of cerebellar-cortical anatomical connectivity the findings are consistent with the hypothesis that the right cerebellum differentially processes high pass filtered information (segmental properties) and the left cerebellum differentially processes low pass filtered information (prosodic, melodic properties). Further research is necessary to examine these hypotheses and their alternatives directly. PMID- 17853078 TI - Developmental increase of total cell numbers in the murine cerebellum. AB - The cerebellum has been widely used as a paradigm to study basic mechanisms of brain development and cortical histogenesis. Its highly regular structure has always made it particularly attractive to approaches relying on, and yielding, quantitative information, which provide a cornerstone of systems-oriented integrative analyses. Astonishingly, though, a systematic quantification of cell generation during cerebellar development has so far not been provided. Here, we use the isotropic fractionator (i.e., cell counts based on tissue homogenates from anatomically defined regions; cf. Herculano-Houzel S, Lent R., J Neurosci. 2005;25:2518-21) to assess the developmental increase of total cell numbers in the murine cerebellum from embryonic day 17 into early adulthood. Our data show that the quantitative increase of cerebellar cell numbers follows a classical, S shaped growth curve as described by the Hill-equation. The adult murine cerebellum was found to comprise a total of (44.03+/-0.42) * 10(6) cells, half of which are generated before postnatal day 12+/-0.18. Consistent results were obtained by using two approaches to cell counting, one based on manual assessment, the other on flow cytometry. These data provide a reliable quantitative description of cerebellar growth in the mouse and define a predictive model that should allow their integration with quantitative and qualitative descriptions of cerebellar development. PMID- 17853080 TI - Spinocerebellar ataxia type 17 is caused by mutations in the TATA-box binding protein. AB - The spinocerebellar ataxia type 17 (SCA17) is characterized by cerebellar ataxia, dementia, and involuntary movements, including chorea and dystonia. In addition, psychiatric symptoms, pyramidal signs, and rigidity are common. MRI shows variable atrophy of the cerebrum, brainstem, and cerebellum. The autosomal dominantly inherited progressive neurodegenerative disorder is caused by an expanded CAA/CAG repeat coding for glutamine. Alleles of the normal range carry 25 to 42 glutamine residues, disease causing alleles 43 to 63. Alleles with 43 to 48 glutamine codons may be associated with incomplete penetrance. The mean age of onset is about 30 years for individuals with full-penetrance alleles, but ranges from three to 55 years. PMID- 17853099 TI - Letter To Editor. PMID- 17853088 TI - N-acetylcysteine and neurodegenerative diseases: basic and clinical pharmacology. AB - Increasing lines of evidence suggest a key role of oxidative stress in neurodegenerative diseases. Alzheimer's disease, Parkinson's disease, myoclonus epilepsy of the Unverricht-Lundborg type, spinocerebellar degeneration, tardive dyskinesia and Down's syndrome have been associated with several mitochondrial alterations. Oxidative stress can decrease cellular bioenergetic capacity, which will then increase the generation of reactive oxygen species resulting in cellular damage and programmed cell death. First, this review examines the mechanisms of action of N-acetylcysteine (NAC), an antioxidant and a free radical scavenging agent that increases intracellular GSH, at the cellular level. NAC can act as a precursor for glutathione synthesis as well as a stimulator of the cytosolic enzymes involved in glutathione regeneration. The chemical properties of NAC include redox interactions, particularly with other members of the group XIV elements (selenium, etc.) and ebselen, a lipid-soluble seleno-organic compound. Second, NAC has been shown to protect against oxidative stress-induced neuronal death in cultured granule neurons. Recent findings on the protective effect of NAC against 4-hydroxynonenal (HNE)-induced toxicity in cerebellar granule neurons are summarized. Finally, the protective pharmacokinetics of NAC in humans and the possible usefulness of NAC for the treatment of neurodegenerative diseases are discussed with reference to basic and clinical studies. PMID- 17853112 TI - Altered olivocerebellar activity patterns in the connexin36 knockout mouse. AB - The inferior olive (IO) has among the highest densities of neuronal gap junctions in the nervous system. These gap junctions are proposed to be the underlying mechanism for generating synchronous Purkinje cell complex spike (CS) activity. Gap junctions between neurons are formed mostly by connexin36 proteins. Thus, the connexin36 knockout (Cx36KO) mouse provides an opportunity to test whether gap junction coupling between IO neurons is the basis of CS synchrony. Multiple electrode recordings of crus 2 CSs were obtained from wildtype (Wt) and Cx36KO mice. Wts showed statistically significant levels of CS synchrony, with the same spatial distribution as has been reported for other species: high CS synchrony levels occurred mostly among Purkinje cells within the same parasagittally oriented cortical strip. In contrast, in Cx36KOs, synchrony was at chance levels and had no preferential spatial orientation, supporting the gap junction hypothesis. CS firing rates for Cx36KOs were significantly lower than for Wts, suggesting that electrical coupling is an important determinant of IO excitability. Rhythmic CS activity was present in both Wt and Cx36KOs, suggesting that individual IO cells can act as intrinsic oscillators. In addition, the climbing fiber reflex was absent in the Cx36KOs, validating its use as a tool for assessing electrical coupling of IO neurons. Zebrin II staining and anterograde tracing showed that cerebellar cortical organization and the topography of the olivocerebellar projection are normal in the Cx36KO. Thus, the differences in CS activity between Wts and Cx36KOs likely reflect the loss of electrical coupling of IO cells. PMID- 17853115 TI - Phocein: A potential actor in vesicular trafficking at Purkinje cell dendritic spines. AB - Phocein is an intracellular protein highly expressed in neurons. It is the major partner of the striatin family members which are scaffolding proteins involved in signaling and trafficking. Due to its association with dynamin via direct interactions with nucleotide diphosphate kinase (NDPK) and EPS15, phocein has been implicated in vesicular trafficking, acting in particular in the endocytic process. This review focuses on immuno-cytochemical studies showing the strict localization of phocein in Purkinje cell dendritic spines involved in excitatory transmission in the cerebellum of postnatal and adult rodents. Immunogold labeling sometimes detects phocein in close vicinity with endocytic-like membrane profiles suggesting that phocein plays a role in endocytosis. Furthermore, co localization of phocein and SG2NA within spines suggests that their interactions have a functional significance in the molecular cascades that underly membrane trafficking in post-synaptic structures. As the striatin family members are highly concentrated in dendritic spines, their interactions with phocein might be involved in mediating synaptic plasticity through spine remodeling by endocytosis. PMID- 17853117 TI - Sacsinopathies: sacsin-related ataxia. AB - Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) was originally found among inhabitants of the Charlevoix-Saguenay region of northeastern Quebec in Canada. This disease is a neurodegenerative disorder characterized by early onset spastic ataxia, dysarthria, nystagmus, distal muscle wasting, finger and foot deformities, and retinal hypermyelination. The principal neuropathology comprises atrophy of the upper vermis and the loss of Purkinje cells in the cerebellum. The SACS gene was originally reported to consist of a single gigantic exon spanning 12.8 kb with an 11.5-kb open reading frame (ORF), and to encode the protein sacsin. Recently, eight exons upstream from the original gigantic one, however, have been found, and the new ORF has elongated to 13.7 kb. To date, at least 28 mutations have been found in Quebec and non-Quebec patients including ones in Italy, Japan, Spain, Tunisia, and Turkey, and ARSACS thus shows a worldwide occurrence. Although most of the mutations reported have been in the gigantic exon, the genotype is now expanding upstream from this gigantic exon. Therefore, the new exons upstream of the gigantic one should be analyzed when a case is clinically compatible with ARSACS, even without any mutation in the gigantic exon. Although Quebec patients show a homogeneous phenotype, non-Quebec patients exhibit some atypical clinical features, as follows: slightly later onset than that in Quebec patients, absence of retinal hypermyelination, intellectual impairment, and lack of spasticity. Thus, since ARSACS shows the clinical diversity, the SACS gene should be analyzed not only in typical cases as Quebec patients but also in atypical cases as non-Quebec patients. As more SACS mutations are identified worldwide, the clinical spectrum of 'sacsinopathies' will expand, and a finer genotype-phenotype correlation study will become possible and shed light on the molecular mechanism underlying ARSACS. PMID- 17853119 TI - Cerebellum and cognition: viewed from philosophy of mind. AB - Traditionally, it is believed, that the primary function of the cerebellum is to coordinate movement. During the past three decades, it has been controversially discussed, whether the cerebellum may also contribute to cognition and mental states like emotions. In this paper, no position relating to this controversy will be taken. Instead, the hypothesis of non-motor functions of the cerebellum will be viewed from the position of the philosophy of mind. The remarkably uniform microscopic structure and neuronal networks of the cerebellum have led to computer analogies by several authors. The main idea of functionalism, i.e., a theory within the philosophy of mind, is that the mental relates to the physical as computer software does to hardware. This raises the question, whether a cerebellar contribution to cognition and mental states would support functionalism in the philosophy of mind. No support of functionalism could be found in this study, investigating the classical philosophical arguments pro and con functionalism such as those of multiple realizability, the Chinese room and the explanatory gap, while taking the results of cerebellar research into account. On the other hand, philosophical reflection suggests a careful use of the phrases "cognitive dysmetria" (Andreasen et al. Proc Natl Acad Sci USA. 1996;93:9985-90) in the context of mental illness and of "dysmetria of thought" (Schmahmann Arch Neurol. 1991;48:1178-87). According to the argument of the explanatory gap there is at present little support for the assumption that the phenomenal experiencing of an altered emotion can be reduced to the dysmetria of movement. PMID- 17853122 TI - Equivalency of Spanish language versions of the trail making test part B including or excluding "CH". AB - Spanish speakers commonly use two versions of the alphabet, one that includes the sound "Ch" between C and D and another that goes directly to D, as in English. Versions of the Trail Making Test Part B (TMT-B) have been created accordingly to accommodate this preference. The pattern and total number of circles to be connected are identical between versions. However, the equivalency of these alternate forms has not been reported. We compared the performance of 35 healthy Spanish speakers who completed the "Ch" form (CH group) to that of 96 individuals who received the standard form (D group), based on whether they mentioned "Ch" in their oral recitation of the alphabet. The groups had comparable demographic characteristics and overall neuropsychological performance. There were no significant differences in TMT-B scores between the CH and D groups, and relationships with demographic variables were comparable. The findings suggest that both versions are equivalent and can be administered to Spanish speakers based on their preference without sacrificing comparability. PMID- 17853123 TI - Individual case analysis of processing speed difficulties in children with and without traumatic brain injury. AB - Two studies were conducted to determine the frequency of processing speed difficulties relative to estimates of other problem-solving abilities in children with and without traumatic brain injury (TBI). The two samples consisted of 213 normally functioning school-age children and 65 TBI children and 19 trauma controls. All children were administered the WISC-III/IV Vocabulary, Block Design, and Coding subtests. The frequency of children in each sample having a Coding subtest score of 3 or 4 scale points below the Vocabulary or Block Design score (whichever one was lower) was calculated. Using a 3-point scale difference, the presence of processing speed deficits relative to other cognitive abilities in the school sample was low (5.2%), and was equivalent to that demonstrated by trauma controls (5.3%). However, in the TBI sample, 18 out of 65 TBI patients (27.7%) showed this same pattern. Using a 4-point discrepancy scale, 3.3% of normal children and 16.9% of TBI children showed this pattern. The frequency of this pattern increased with severity of TBI, using two different but related classification systems. These preliminary findings require cross validation in a larger sample before definite conclusions can be reached. PMID- 17853124 TI - The relationship of IQ to effort test performance. AB - The relationship between IQ and nine effort indicators was examined in a sample of 189 neuropsychology clinic outpatients who were not in litigation or attempting to obtain disability. Participants with the lowest IQ (50-59) failed approximately 60% of the effort tests, while patients with an IQ of 60 to 69 failed 44% of effort indicators, and individuals with borderline IQ (70 to 79) exhibited a 17% failure rate. All patients with IQ < 70 failed at least one effort test. Cutoffs for the Warrington Recognition Memory Test (Words) and Finger Tapping maintained the highest specificities in low IQ samples. PMID- 17853125 TI - A componential analysis of proverb interpretation in patients with frontal lobe epilepsy and temporal lobe epilepsy: relationships with disease-related factors. AB - The ability to interpret nonliteral, metaphoric language was explored in patients with frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE), and matched control participants, to determine (1) if patients with FLE were impaired in their interpretations relative to those with TLE and controls, and (2) if disease related variables (e.g., age of seizure onset) predicted performances in either patient group. A total of 22 patients with FLE, 20 patients with TLE, and 23 controls were administered a test of proverb interpretation to assess their ability to grasp the abstract meaning of nonliteral language. Participants were presented with a series of proverbs and asked to provide an oral interpretation of each. Responses to each proverb were scored according to their accuracy and level of abstractness. Patients with FLE, but not TLE, were impaired relative to controls in their overall interpretation of proverbs. However, a subgroup analysis revealed that only patients with left FLE showed impaired interpretation accuracy relative to the other groups, whereas patients with both left FLE and left TLE showed impaired abstraction. Patients with FLE were also impaired when they were asked to select the best interpretation of the proverb from response alternatives. In patients with FLE, only a left-sided seizure focus was associated with poorer performance. In patients with TLE, both an early age of onset and a left-sided seizure focus predicted poorer performance. Overall, FLE patients exhibit greater impairment than TLE patients in interpreting proverbs. However, the nature and disease-specific correlates of impaired performances in proverb interpretation differ between the groups. PMID- 17853126 TI - Distinguishing between neuropsychological malingering and exaggerated psychiatric symptoms in a neuropsychological setting. AB - It is unclear whether symptom validity test (SVT) failure in neuropsychological and psychiatric domains overlaps. Records of 105 patients referred for neuropsychological evaluation, who completed the Test of Memory Malingering (TOMM), Reliable Digit Span (RDS), and Millon Clinical Multiaxial Inventory-III (MCMI-III), were examined. TOMM and RDS scores were uncorrelated with MCMI-III symptom validity indices and factor analysis revealed two distinct factors for neuropsychological and psychiatric SVTs. Only 3.5% of the sample failed SVTs in both domains, 22.6% solely failed the neuropsychological SVT, and 6.1% solely failed the psychiatric SVT. The results support a dissociation between neuropsychological malingering and exaggeration of psychiatric symptoms in a neuropsychological setting. PMID- 17853127 TI - Validity testing in dually diagnosed post-traumatic stress disorder and mild closed head injury. AB - Prospects for the coexistence of post-traumatic stress syndrome (PTSS) and mild traumatic brain injury (mTBI) rely exclusively on subjective evidence, increasing the risk of response bias in a compensatable social context. Using a priori specificities derived from genuine brain disorder groups, we examined validity failure rates in three domains (symptom, cognitive, motor) in 799 persons reporting persistent subjective disability long after mild neurological injury. Validity tests included the Test of Memory Malingering, MMPI-2 Fake Bad Scale, and Infrequency (F) scales, reliable digit span, and Halstead-Reitan finger tapping. Analyses showed invalidity signs in large excess of actuarial expectations, with rising invalidity risk conditional on post-traumatic complexity; the highest failure rates were produced by the 95 persons reporting both neurogenic amnesia and re-experiencing symptoms. We propose an "over endorsement continuum" hypothesis: The more complex the post-traumatic presentation after mild neurological injury, the stronger the association with response bias. Late-appearing dual diagnosis is a litigation phenomenon so intertwined with secondary gain as to be a byproduct of it. PMID- 17853128 TI - Exploring the validity of the comprehensive trail making test. AB - The present study is the first independent investigation of the Comprehensive Trail Making Test (CTMT; Reynolds, 2002) with both clinical and non-clinical samples. We examined convergent and divergent validity by exploring relationships between the CTMT and other measures. Discriminant validity was examined by comparing CTMT scores of non-clinical and clinical groups. Results indicate that the CTMT was largely unrelated to measures of processing speed and nonverbal reasoning, verbal processing, and psychiatric symptoms. The CTMT Composite score was able to differentiate between clinical and non-clinical groups with a large effect size. Overall, although further research is needed, results tentatively suggest that the CTMT may be a useful addition to a multifaceted neuropsychological test battery. PMID- 17853129 TI - Activity-based prospective memory in schizophrenia. AB - The study reports activity-based prospective memory as well as its clinical and neuropsychological correlates in schizophrenia. A total of 42 persons diagnosed with schizophrenia and 42 healthy controls were administered prospective memory, set-shifting, and verbal working memory tasks. The schizophrenia group was additionally administered various psychopathology rating scales. Group differences, with poorer performances of the schizophrenia group, were observed on the measures of prospective memory, working memory, and set shifting. The performance on prospective memory tasks correlated with the performance levels on verbal working memory and set-shifting tasks but not with the clinical measures. This study demonstrated impaired activity-based prospective memory in schizophrenia. The impairment can be due to deficits in various neuropsychological domains. PMID- 17853130 TI - Using the Wechsler Memory Scale-III to detect malingering in mild traumatic brain injury. AB - This study examined the classification accuracy of the WMS-III primary indices in the detection of Malingered Neurocognitive Dysfunction (MND) in Traumatic Brain Injury (TBI) using a known-groups design. Sensitivity, specificity, and positive predictive power are presented for a range of index scores comparing mild TBI non malingering (n = 34) and mild TBI malingering (n = 31) groups. A moderate/severe TBI non-malingering (n = 28) and general clinical group (n = 93) are presented to examine specificity in these samples. In mild TBI, sensitivities for the primary indices ranged from 26% to 68% at 97% specificity. Three systems used to combine all eight index scores were also examined and all achieved at least 58% sensitivity at 97% specificity in mild TBI. Specificity was generally lower in the moderate/severe TBI and clinical comparison groups. This study indicates that the WMS-III primary indices can accurately identify malingered neurocognitive dysfunction in mild TBI when used as part of a comprehensive classification system. PMID- 17853131 TI - Executive functioning and observed versus self-reported measures of functional ability. AB - This study investigated the relationship between measures of executive functioning and both observed and self-reported functional ability. It was hypothesized that performance on a direct assessment of functional ability would have a stronger correlation with performance on measures of executive functioning than a self-report measure of functional ability. Results supported the hypothesis, indicating that self-report measures may not be sensitive to early decline in functional ability. Results also provide evidence to support the use of measures of executive functioning to detect early decline in functional ability that otherwise may not be detected by the typical self-report measures used in clinical settings. While lack of insight into functional deficits has been demonstrated in the literature in older adults with dementia, this study demonstrated lack of insight in a non-demented, community dwelling sample of older adults. PMID- 17853132 TI - Reliability and validity of the Spanish Language Wechsler Adult Intelligence Scale (3rd Edition) in a sample of American, urban, Spanish-speaking Hispanics. AB - The utility of the Spanish WAIS-III was investigated by examining its reliability and validity among 100 Spanish-speaking participants. Results indicated that the internal consistency of the subtests was satisfactory, but inadequate for Letter Number Sequencing. Criterion validity was adequate. Convergent and discriminant validity results were generally similar to the North American normative sample. Paired sample t-tests suggested that the WAIS-III may underestimate ability when compared to the criterion measures that were utilized to assess validity. This study provides support for the use of the Spanish WAIS-III in urban Hispanic populations, but also suggests that caution be used when administering specific subtests, due to the nature of the Latin America alphabet and potential test bias. PMID- 17853133 TI - Automated neuropsychological assessment metrics (ANAM) and Woodcock-Johnson III Tests of Cognitive Ability: a concurrent validity study. AB - This study examines the relationship between a computerized neuropsychological assessment battery, the Automated Neuropsychological Assessment Metrics (ANAM) and a widely used ability measure, Woodcock-Johnson III Tests of Cognitive Ability (WJ-III). Results indicated substantial relationship between the ANAM throughput (accuracy/response time) scores and the WJ-III Cognitive Efficiency cluster. An unexpectedly strong relationship was evident between accuracy scores on the ANAM Logical Reasoning scale and the WJ-III General Intellectual Ability score, purporting to measure the g factor. The findings support the viability of the ANAM as a time- and cost-effective tool for appraisal of cognitive function. PMID- 17853135 TI - Persistent symptoms associated with factors identified by the WHO Task Force on Mild Traumatic Brain Injury. AB - The current study examined the role of factors identified by the World Health Organization's Task Force on Mild Traumatic Brain Injury as being associated with poor outcome after mild traumatic brain injury. Employing symptom severity ratings at 3 months post-injury greater than "mild," subgroups of Higher-Severity (20%) and Lower-Severity (80%) participants were identified. Findings revealed that individuals who report greater symptom complaints at 3 months post-MTBI may be identifiable soon after injury on the basis of the magnitude and severity of early self-reported symptoms, pre-morbid psychological issues, and involvement in compensation-seeking. Injury severity factors did not differ between the groups. PMID- 17853134 TI - Comparability of neuropsychological test profiles in patients with chronic substance abuse and mild traumatic brain injury. AB - The purpose of this study was to compare 104 patients with acute uncomplicated mild traumatic brain injury (MTBI) to a sample of 104 patients from an inpatient substance abuse program to determine whether these patients could be differentiated by their pattern of relative cognitive strengths and weaknesses. Patients were matched on age, education, and gender. Eight cognitive measures were used that included tests of attention, memory, and processing speed. There were no statistically significant differences between the two groups on any of the cognitive measures. Using a two-step cluster analysis procedure (i.e., hierarchical and k-means analyses), seven common profiles were identified. There was no significant difference in the proportions of patients from the MTBI or substance abuse group in each of the seven profiles. These results show that patients with uncomplicated MTBIs could not be reliably differentiated from patients with substance abuse problems on these cognitive measures. This is of particular concern for clinicians evaluating the neuropsychological effects of MTBI in individuals with a comorbid history of substance abuse. PMID- 17853136 TI - Comparison of the Morel Emotional Numbing Test for Posttraumatic Stress Disorder to the Word Memory Test in neuropsychological evaluations. AB - The most commonly feigned cognitive and psychiatric disorders for survivors of traumatic injury are memory dysfunction and posttraumatic stress disorder (PTSD). The position of the National Academy of Neuropsychology is that symptom validity tests (SVTs) should be part of any comprehensive neuropsychological evaluation. In this article the Morel Emotional Numbing Test for Posttraumatic Stress Disorder (MENT), a SVT for PTSD, was compared to a SVT for memory, the Word Memory Test (WMT). Available archival data on 216 consecutive referrals for neuropsychological evaluations at the Veterans Affairs Tennessee Valley Healthcare System were reviewed. Of the total records reviewed 37 patients had been administered both the MENT and the WMT. The clinically recommended cutoff on the WMT was used as the main criterion to classify patients into two groups: simulating impairment or credible. The results indicated that the simulating impairment group had significantly more errors on the MENT than the credible group did (p <.0001). The criterion-related characteristics of the MENT in assessing response bias in relation to the WMT were confirmed Clinical and research implications of the utilization of the MENT are discussed in this study. PMID- 17853137 TI - Accuracy of clinical neuropsychological versus statistical prediction in the classification of seizure types. AB - Many studies have reported on the pattern of neuropsychological test performance across varied seizure diagnosis populations. Far fewer studies have evaluated the accuracy of the clinical neuropsychologist in formulating an impression of the seizure diagnosis based on results of neuropsychological assessment, or compared the accuracy of clinical neuropsychological judgment to results of statistical prediction. Accuracy of clinical neuropsychological versus statistical prediction was investigated in four seizure classification scenarios. While both methods outperformed chance, accuracy of clinical neuropsychological classification was either equivalent or superior to statistical prediction. Results support the utility and validity of clinical neuropsychological judgment in epilepsy treatment settings. PMID- 17853138 TI - Development of the Texas Spanish Naming Test: a test for Spanish speakers. AB - Neuropsychological assessment of Spanish speakers often involves translated versions of English measures, with limited validation data and potential bias due to cultural, educational, and linguistic differences. The Texas Spanish Naming Test (TNT), a 30-item confrontation naming test, was developed for Spanish speakers by systematically selecting culturally salient words. In a sample of 85 minimally educated Spanish speakers, the TNT demonstrated good internal consistency and convergent validity, and showed greater sensitivity than a translated version of the popular Boston Naming Test. Results support the clinical utility of the TNT when dementia among Spanish speakers is suspected. PMID- 17853139 TI - Alternative to the Stroop Color-Word Test for illiterate individuals. AB - An alternative to the Stroop Color-Word Test (SCWT), denominated the Colored Numbers Test (CNT), was developed to evaluate the selective attention of illiterate individuals. A total of 30 volunteers with basic education (control group) and 30 illiterate volunteers (experimental group) performed the SCWT and the CNT. Volunteers had to name the color of the rectangles in the CNT neutral condition, and in the critical condition they had to either name the color of the numbers or, when the numbers were black, read the numbers. An interference index (II) was calculated for both tests by subtracting the time taken to complete the task in the neutral condition from the time taken to complete the task in the critical condition. The control group showed an II of 14.9 s in the SCWT and of 19.1 s in the CNT, and the experimental group, which practically presented no interference in the SCWT (II = 0.2 s), showed an II of 18.7 s in the CNT. These findings suggest that the CNT can be used to evaluate selective attention. Further work should confirm its validity. Its advantage over the SCWT is that it does not depend on the ability to read words, being then suitable for illiterate individuals. PMID- 17853140 TI - A normative study of the Boston Naming Test in 3- to 14-year-old Korean children. AB - We administered the 60-item Korean version of the Boston Naming Test (K-BNT) to 2560 normally developing Korean children aged between 3 and 14 years. The children were stratified into 24 groups between the ages of 3 years, 0 months (3;0) and 14 years, 11 months (14;11) with 6-month intervals between each group. Statistical analysis did not reveal gender differences, but there were significant age differences among the groups (F = 615.340, p = .000). The lowest score (M = 14.17, SD = 4.28) was observed in the 3;0 to approximately 3;5 age group and the highest (M = 50.64, SD = 3.70) in the 14;6 to approximately 14;11. Simple linear regression analysis revealed an R2 value of .800, indicating that the age variable explains 80% of the score variance (F = 10228.343, p = .000). Some of the 24 age groups were clustered due to lack of difference of the test scores between the neighboring groups, reducing the number of age groups to 13. This large cross-sectional study provided clinically useful norms of the BNT on Korean children and confirmed an importance of the age parameter in a neuropsychological testing. PMID- 17853141 TI - Cognitive approach to the assessment of limb apraxia. AB - A new instrument for the assessment of the different levels of gesture processing, as identified by recent cognitive models of apraxia, is presented. The battery comprises thirteen tasks -- eight assess the production of meaningful gestures both on command and on imitation, four tasks assess the ability to recognize and identify gestures, and one task assesses imitation of meaningless gestures. The battery encompasses a novel test of gesture production on visual command. A total of 60 healthy British volunteers were tested with the entire battery. On the whole, participants made more errors with pantomimes than with other tasks. Their scores served as norms. PMID- 17853142 TI - Cross-validation of a manual form of the Letter Memory Test using a known-groups methodology. AB - A manual form of the Letter Memory Test (LMT: Orey, Cragar, & Berry, 2000) was compared in neuropsychological evaluees classified as honest (HON: n = 39) or probable cognitive feigners (PCF: n = 10) using results from two well-validated motivational tests. With the exception of lower educational level and higher rate of compensation seeking in the PCF, the groups were equivalent on most important demographic and injury severity parameters. PCF participants scored significantly lower on most neuropsychological tests (median Cohen's d = 1.2), as well as on the manual LMT (Cohen's d = 4.2). Operating characteristics of the manual LMT in the present sample were comparable to those reported in a similar study using the computerized version of the LMT in neuropsychiatric patients (Vagnini et al., 2006). PMID- 17853143 TI - The repeatable battery for the assessment of neuropsychological status (RBANS): clinical utility in a traumatic brain injury sample. AB - The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS; Randolph, 1998), a neuropsychological screening measure initially designed to assess the cognitive deficits associated with dementia, has since been clinically implemented with other neurological populations including traumatic brain injury (TBI). This study evaluated the clinical utility of the RBANS in a TBI population by comparing the profiles of 51 TBI cases and 34 non-head-injured controls. Across RBANS' Index Scores, the TBI group performed at a significantly lower level than the controls; sensitivity to TBI and likelihood ratios ranged from modest to strong; and specificity was high. Particularly efficacious was the clinical efficiency exhibited by the Total Scale Index (summary score) of the RBANS. PMID- 17853144 TI - A diary study of action slips in healthy individuals. AB - Memory complaints following minor head injury or whiplash are common and often bear similarity to absent mindedness or action slips (Reason, 1979). We replicated Reason's study by asking 189 healthy volunteers to keep diaries of their action slips for a week. The mean number of slips was 6.4 (SD = 4.9). Perceived stress did not correlate with number of slips but there was a weak positive correlation between action slips and scores on a memory failures questionnaire. Memory diaries may be clinically useful when assessing individuals who worry about cognitive sequelae of minor injuries. Diaries clarify the nature of the complaints and may have therapeutic value by demonstrating that the memory slips are less frequent than estimated by the patients. PMID- 17853145 TI - Construct validity of the Wisconsin Card Sorting Test-64 in patients with stroke. AB - This study examined the factor structure and contrasted-group validity of the Wisconsin Card Sorting Test-64 (WCST-64) in a stroke sample (n = 112). Confirmatory factor analyses were used to compare five different models suggested by prior factor analyses. The results indicated that the WCST-64 was best represented by a three-dimensional model comprising response inflexibility (factor 1), ineffective hypothesis-testing strategy (factor 2), and set maintenance (factor 3). A significant overall multivariate effect for group (F = 2.87, df = 18,495.46, p <.001) was found in a multivariate analysis of covariance with WCST scores as dependent variables and four different groups (three stroke subgroups with different levels of cognitive function and a normal control group) as independent variable, after controlling for gender. The results of discriminant analysis supported the use of the WCST-64 in stroke patients with cognitive impairment. PMID- 17853147 TI - Exploring age-related decline on the Wisconsin Card Sorting Test. AB - It is well established that performance on the Wisconsin Card Sorting Test (WCST) tends to decline with advanced age, but the reason for this decline has not been established. The objective of the present study was to clarify this question using a qualitative approach to the task. The WCST was administered to 19 older adults and 25 younger participants. In addition to standard testing procedures, all participants were asked to verbalize their response strategy when placing each card. Results of this procedure implicate poor set shifting and set maintenance, consistent with reduced efficiency of feedback utilization, as the primary cause for age-related decline on the WCST. PMID- 17853146 TI - Is the prefrontal cortex important for fluid intelligence? A neuropsychological study using Matrix Reasoning. AB - Patients with prefrontal damage and severe defects in decision making and emotional regulation often have a remarkable absence of intellectual impairment, as measured by conventional IQ tests such as the WAIS/WAIS-R. This enigma might be explained by shortcomings in the tests, which tend to emphasize measures of "crystallized" (e.g., vocabulary, fund of information) more than "fluid" (e.g., novel problem solving) intelligence. The WAIS-III added the Matrix Reasoning subtest to enhance measurement of fluid reasoning. In a set of four studies, we investigated Matrix Reasoning performances in 80 patients with damage to various sectors of the prefrontal cortex, and contrasted these with the performances of 80 demographically matched patients with damage outside the frontal lobes. The results failed to support the hypothesis that prefrontal damage would disproportionately impair fluid intelligence, and every prefrontal subgroup we studied (dorsolateral, ventromedial, dorsolateral + ventromedial) had Matrix Reasoning scores (as well as IQ scores more generally) that were indistinguishable from those of the brain-damaged comparison groups. Our findings do not support a connection between fluid intelligence and the frontal lobes, although a viable alternative interpretation is that the Matrix Reasoning subtest lacks construct validity as a measure of fluid intelligence. PMID- 17853148 TI - A panel interview on the ethical practice of neuropsychology. AB - Neuropsychologists who have considerable experience reflecting, presenting, publishing, and advising on ethical matters are a rich resource for clinicians who have ethics questions. Consultation with such colleagues can be an important part of the ethical decision-making process. The purpose of the present article is to provide the opinions and perspectives of three neuropsychologists who, based on their experience and scholarly activities, served as panelists regarding ethical matters. Although the advice and opinions of colleagues are not a substitute for familiarity with relevant ethical requirements, guidelines, and professional literature, they offer valuable information that enhances the ethical decision-making process. PMID- 17853149 TI - Predicting cognitive change across 3 years in community-dwelling elders. AB - The determination of clinically significant cognitive change across time is an important issue in neuropsychology, and repeated assessments are common with older adults. Regression-based prediction formulas, which use initial test performance and demographic variables to predict follow-up test performance, have been utilized with patient and healthy control samples. Comparisons between predicted and observed follow-up performances can assist clinicians in determining the significance of change in the individual patient. In the current study, multiple regression-based prediction equations for the five Indexes and Total Score of the RBANS were developed for a sample of 146 community-dwelling older adults across a 2-year interval. These algorithms were then validated on a separate elderly sample (n = 145). Minimal differences were present between Observed and Predicted follow-up scores in the validation sample, suggesting that the prediction formulas are clinically useful for practitioners who assess older adults. A case example is presented that illustrates how the algorithms can be used clinically. PMID- 17853150 TI - Detecting response bias with performance patterns on an expanded version of the Controlled Oral Word Association Test. AB - The present study investigated whether speeded word generation performance patterns seen in healthy subjects are also produced in genuine and feigned traumatic brain injury (TBI). An expanded version of the Controlled Oral Word Association Test was administered to healthy controls, TBI patients, simulated malingerers, and probable clinical malingerers. Four performance patterns were operationalized. Three of these patterns were replicated in the healthy control sample and found to be unaltered by genuine TBI. They were then combined into a logistic regression model that discriminated well between examinees who put forth adequate effort and those who evidenced response bias. PMID- 17853151 TI - Malingering on the social security disability consultative exam: predictors and base rates. AB - The Disability Determinations Service (DDS) obtains evidence about an applicant from sources that may include the Psychological Consultative Examination (PCE), which usually includes a mental status examination and Wechsler Scale findings. Although evidence for good effort is necessary to validate the findings, psychologists have been officially discouraged from determining effort by the use of formal tests. In Chafetz, Abrahams, and Kohlmaier (2007), indicators of effort within the PCE in WAIS-age (adults) and WISC-age (children) claimants were determined, and a PCE Malingering Rating Scale was developed. In the present study, this new scale was used along with established symptom validity tests (SVTs) to determine base rates and additional predictors of malingering within the PCE. Claimants were apportioned into separate effort groups in a "dose response" manner: Definite Malingerers, Chance-Level, Fail Both (SVT and Rating Scale), Fail One, Fail Indicators, and Not Fail. Data from separate studies using the Test of Memory Malingering (TOMM), and the Medical Symptom Validity Test (MSVT) were used to assign claimants into separate effort groups. An evidence based assessment approach utilized these base-rates to calculate post-test odds. Other predictors of effort within the PCE include the presence of conduct disorder symptoms, and the number of other family members on Disability. PMID- 17853152 TI - Review of normative data for common screening measures used to evaluate cognitive functioning in elderly individuals. AB - When conducting neuropsychological evaluations of the elderly, it is important to compare patients' test scores to appropriate normative data to maximize diagnostic and descriptive accuracy. Many sets of normative data are now available for screening measures that assess cognitive functioning in the elderly. This article systematically reviewed available norms for 6 widely used screening measures of cognitive functioning in elderly patients. Details regarding the sample characteristics and data collection methods are provided for each set of norms, thereby providing a useful reference for clinicians. PMID- 17853153 TI - "Psychometric intelligence" is not equivalent to "crystallized intelligence," nor is it insensitive to presence of brain damage: a reply to Russell. AB - Whether Halstead's (1947) distinction between biologic and psychometric intelligence and Cattell's (1963) theory of fluid and crystallized intelligence reflect the same underlying constructs is an interesting question and has heuristic value. To address that question experimentally, however, requires factor-analytic and other higher-order correlative analysis with careful clinical syndrome characterization. We argue that Halstead's and Cattell's characterizations of test attributes into distinct domains are not equivalent, and that the proposal of their equivalence cannot be properly evaluated based solely on test battery sensitivity to brain damage. PMID- 17853154 TI - Age-related differences in executive function among children with spina bifida/hydrocephalus based on parent behavior ratings. AB - Previous research has suggested that adolescents with myelomeningocele and shunted hydrocephalus (MMH) have difficulties with aspects of executive functioning and, in turn, with functional independence. There is little research, however, examining patterns of executive functioning across adolescence in this population. The goal of this cross-sectional study was to examine parent ratings of executive function in children with MMH and in typically developing peers across late childhood and adolescence. Parents of 36 individuals with MMH and 35 typically developing peers, ages 10 to 18 years, completed the Behavior Rating Inventory of Executive Function (BRIEF). The BRIEF is organized into eight scales and two primary indices-Metacognition (MCI) and Behavioral Regulation (BRI). As a whole, the children with MMH had significantly higher BRIEF T-scores, as well as a higher prevalence of clinically significant T-scores across subscales, particularly those representing cognitive control. Effects of group, age, and age by-group interactions on the mean raw scores of the MCI and BRI were examined using regression analyses. There were significant group effects (p <. 05) for both the BRI and MCI, with the controls having significantly lower mean ratings than the MMH group. There was also a significant contribution of age-by-group interaction on the BRI (p <. 05). Although mean raw scores on the BRI for the MMH group remained stable across ages, mean raw scores in the control group decreased as age increased. Thus, healthy children have age-related improvements in executive control behaviors across adolescence, particularly behavioral control, while children with MMH demonstrate no age-related improvements in parent reported executive behaviors across adolescence. Therefore, children with MMH may continue to require targeted interventions and modifications to address executive dysfunction into young adulthood in order to promote functional independence. PMID- 17853155 TI - Effective normative samples for the detection of cognitive impairment in older adults. AB - The inclusion of individuals with incipient dementia in normative data contaminates the distinction between normal and pathological aging. Conventional and Robust (excluding persons with incipient dementia) norms were created using data from the Canadian Study of Health and Aging (CSHA). Robust norms were not significantly better at distinguishing between normal and pathological aging. Norms reflecting the relationship between age and the prevalence of dementia revealed a probability of dementia of less than 35%. The results of the norming procedure serve to illustrate the validity of our current measures and methods for identifying cognitive impairment. CSHA Conventional norms are adequate for the identification of cognitive impairment. PMID- 17853156 TI - Adolescents: is there an association between knowledge of oral contraceptives and profession of provider? AB - Knowledge about oral contraceptives (OCs) was investigated among young users of OCs by profession of provider, namely, physician or public health nurse. A 44 item questionnaire designed to assess communication about contraception and knowledge of OCs was distributed to students in 11 of 13 high schools in Trondheim, Norway. Data from 688 OC users were eligible for analyses. Knowledge about OCs was measured by means of 15 questions, from which scores on three separate indices and a total index were determined. Separate indices included knowledge about physical changes during OC use (index I), knowledge about the pill's relative efficacy (index II) and knowledge about risks of cancer/ thromboembolism (index III). Logistic regression analyses showed that high scores with regard to knowledge indices were predicted by sexual activity and communication about contraception with peers and/or parents. Profession of provider was not associated with high knowledge scores. Information given during brief and annual discussions with health professionals appears to have an insignificant impact as compared with information from other sources. Our results plead for an over-the-counter practice. PMID- 17853157 TI - Knowledge and attitude of married Turkish men regarding family planning. AB - OBJECTIVES: Men play an essential role in reproduction. They should be encouraged to involve themselves in birth control, particularly in developing countries, where contraceptive goals have not been reached. This study, carried out in Mus, Turkey, was aimed at determining the attitudes and behaviour of married men with regard to family planning (FP). METHODS: The study included 317 married men aged 20-56 who worked in an institution. Questionnaires were distributed to the participants at their workplace and collected after 30-40 minutes. RESULTS: The use of FP was approved by 78.9% of the men, but a contraceptive method was actually applied by only 65.6%. Whereas 27.6% of the high school and university graduates had five or more children, as many as 67.4% of the men with a lesser educational level had such a large offspring. Nearly 60% of the men had been given information about FP by healthcare professionals. CONCLUSION: Education has a great impact on knowledge and attitudes about FP. PMID- 17853158 TI - Sublingual versus vaginal misoprostol for cervical ripening PRIOR TO manual vacuum aspiration under local anaesthesia: a randomized study. AB - OBJECTIVE: To compare the effectiveness of sublingual and vaginal misoprostol application for cervical ripening prior to manual vacuum aspiration (MVA) under local anaesthesia for voluntary termination of pregnancy between 7 and 10 weeks of gestation. MATERIALS AND METHODS: Prospective randomized study in which 72 women were randomly assigned to administration of either 400 microg vaginal misoprostol 3 hours prior to or 200 microg sublingual misoprostol 2 hours prior to the surgical procedure. We took the preoperative cervical dilatation that was achieved as the main outcome measure. The duration of the procedure, intra operative blood loss, pain perception before and during the operation, patients' satisfaction, side effects and duration of post-operative bleeding were secondary outcome measures. RESULTS: A similar pre-operative cervical dilatation was achieved in the sublingual and the vaginal groups (6.9 +/- 1.6 mm and 6.6 +/- 1.1 mm, respectively; p = 0.3). The duration of the operation, intra-operative blood loss, and patients' satisfaction did not differ between the two groups. Pain scores were significantly higher in the sublingual group than in the vaginal group, both after administration of misoprostol (p = 0.02) and during the procedure (p = 0.02). Nausea and vaginal spotting were significantly more frequent (p = 0.01 and p = 0.003, respectively), but post-operative bleeding significantly shorter (p = 0.003) in the sublingual group. CONCLUSION: Administration of 200 microg sublingual misoprostol 2 hours before suction curettage under local anaesthesia was as effective as 400 microg vaginal misoprostol 3 hours before that procedure with regard to achieving cervical dilatation. It resulted in higher pre-operative and intra-operative pain scores without changing patients' satisfaction. PMID- 17853159 TI - The effects of an oestrogen-free, desogestrel-containing oral contraceptive in women with cyclical symptoms: results from two studies on oestrogen-related symptoms and dysmenorrhoea. AB - OBJECTIVES: To evaluate the effects of an oestrogen-free oral contraceptive (Cerazette; 75 mcg/day desogestrel) in women with oestrogen-related symptoms during previous combined oral contraceptive (COC) use (ERS study) and in women with dysmenorrhoea (DYS study). METHODS: Two similarly designed prospective, non comparative multicentre observational studies were carried out in Germany. Altogether, 403 women with oestrogen-related symptoms during previous COC use and 406 women with dysmenorrhoea took Cerazette continuously. Symptom-related assessments were made at baseline and after 3-4 months, along with bleeding pattern and treatment satisfaction. RESULTS: In the ERS study, the four oestrogen related symptoms studied resolved or improved in over 70% of women. Nausea improved/resolved most (92% of women), followed by breast tenderness (90%), oestrogen-related headache (84%) and oedema (74%). In the DYS study, dysmenorrhoea resolved or considerably improved in 93% of the study population. Correspondingly, use of analgesics dropped from 70% of women at baseline to 8% at study end. Adverse events were reported by 7-8% of both study populations and were mainly bleeding irregularities. Most women in both studies were satisfied with treatment (approximately 90%) and wished to continue treatment after study completion (approximately 85%). CONCLUSIONS: Cerazette in this study set-up improved oestrogen-related symptoms and dysmenorrhoea in women affected and treatment was well accepted. PMID- 17853160 TI - Breast-feeding pattern and onset of menstruation among Yoruba mothers of South west Nigeria. AB - OBJECTIVE: To determine the breast-feeding practices and duration of lactational amenorrhoea among women within the first year of delivery in a Nigerian population. METHOD: Cross-sectional study carried out between January 2005 and April 2006, among mothers within one year of delivery, who were attending the Infant Welfare Clinic at Wesley Guild Hospital, Ilesa, Nigeria. Using a semi structured questionnaire, mothers were interviewed to obtain information regarding their socio-demographic characteristics, parity, breast-feeding habits, use of contraception and onset of menstruation after delivery. Information obtained was analysed using the Statistical Package for Social Sciences (SPSS) software version 11. RESULTS: All 268 (100%) mothers interviewed breast-fed their babies, 261 (97.4%) of which for at least 6 months. Most (71.6%) suckled exclusively for 6 months and more; only 10 (3.7%) never carried out exclusive breast-feeding. Age, parity and educational level did not affect the duration of exclusive breast-feeding. Lactational amenorrhoea lasted 3 months or more in 229 (85.5%) of the mothers. Of the 174 who exclusively breast-fed for 6 months, 109 (62.6%) remained amenorrhoeic during that time and, hence, met the criteria for use of LAM contraception. CONCLUSION: Exclusive breast-feeding among nursing mothers is highly prevalent among Yoruba mothers of South-west Nigeria. Since lactational amenorrhoea lasts 6 months in about two-thirds of the women nursing for that period of time, there is a great potential for the application of LAM for contraception. PMID- 17853161 TI - Women's reproductive autonomy and barriers to contraceptive use in Pakistan. AB - OBJECTIVE: To determine through the log-linear model analysis technique the impact of women's reproductive autonomy, spouses' educational background and other factors on the use of contraception in Pakistan. METHODS: Data from the Pakistan Reproductive Health and Family Planning Survey 2000 were used. In this survey a national sample of married women aged 15-49 years (n = 6579) were interviewed. A number of socio-economic, socio-demographic and women's reproductive autonomy variables were taken for the log-linear model fitting and analysis, in order to examine the impact of women's reproductive autonomy on contraceptive use and the factors affecting this latter. RESULTS: On the basis of partial and marginal association tests, two hierarchical log-linear models were selected. The first one concerned women's reproductive autonomy and contraceptive use, the second one analysed factors affecting contraceptive use. Standardized values of the model's parameter estimates showed that women's reproductive autonomy was significantly associated with husband-wife education attainment when they were using contraception. In the second model, contraceptive use was strongly associated with women's education, husband's desire for more children, sex preference for the next child and number of living children. CONCLUSION: An improved husband-wife educational level results in greater reproductive autonomy of the women and an increased use of contraception. The husband's desire for more children, a preference for the sex of the next child, and the woman's poor education attainment level are the main barriers to contraceptive use. PMID- 17853162 TI - Cycle control, tolerability, efficacy and acceptability of the vaginal contraceptive ring, NuvaRing: results of clinical experience in Germany. AB - OBJECTIVES: To investigate the real-life clinical experience of NuvaRing users in Germany. METHODS: An open-label, prospective, uncontrolled, non-randomized, multicentre postmarketing surveillance study was conducted by 1204 gynaecologists amongst 5823 women requesting contraception. The women underwent routine examinations and contraceptive counselling, and were assessed after three and six cycles of NuvaRing use. RESULTS: Good cycle control was observed and there was a reduction in cycle irregularity and inter-menstrual bleeding, bleeding duration and intensity, and dysmenorrhoea. NuvaRing was well tolerated, and had no significant effect on body weight or blood pressure. Nine women became pregnant unintentionally (two had conceived before they started to use NuvaRing, three due to non-compliance, one because of repeated ring expulsion/loss and three during treatment in spite of having applied this latter as instructed). Most women expressed their satisfaction with NuvaRing; 82% were 'very satisfied/ satisfied', 72% planned to continue using it and 82% would recommend it to others. More than 90% of women found NuvaRing 'without problems/easy' to insert and to remove, and more than 80% of the women and their partners were not disturbed by its presence during intercourse. CONCLUSION: NuvaRing is a highly effective and acceptable method of once-monthly contraception that is safe and well tolerated. PMID- 17853163 TI - Knowledge and practice of contraception among Greek female medical students. AB - OBJECTIVE: In Greece, modern contraceptive methods are used on a limited scale. This study aimed to investigate the knowledge as well as the practice of contraception among female medical students in Greece. STUDY DESIGN: Knowledge and practice of contraception of 102 female graduating medical students were assessed with a self-administered, anonymous questionnaire. RESULTS: Most students were using condoms as the only contraceptive method (45.1%) and 16.7% were not applying any contraceptive method at all. Oral contraceptives were used as only contraceptive means by 4.9% of the students and in combination with condoms by another 4.9%. Condoms were thought to be the most effective contraceptive method available by 28.4% of the students, whereas 4.9% responded that they did not consider any contraceptive method to be effective. Only 55.9% of the students had ever asked their gynaecologist about contraception. CONCLUSION: Much more time should be spent in teaching contraception in the Greek medical schools to ensure the delivery of adequate family planning guidance by future practitioners. PMID- 17853164 TI - Medical abortion in the first trimester: the use of serum hCG and endometrial thickness as markers of completeness. AB - OBJECTIVE: The combination of mifepristone and misoprostol is an established method for induction of early first trimester abortion, but there is no consensus about the best evaluation of treatment outcome. We assessed endometrial thickness, determined by ultrasound and serum-human chorionic gonadotropin (s hCG) as markers of successful management. METHODS: Prospective trial involving 255 women, with a gestation of 62 days or less, who were to undergo medical abortion. In addition to our established routines of performing clinical and ultrasound examinations, we also determined the s-hCG level prior to treatment and at follow-up. RESULTS: Of the 255 subjects treated during the study, 20 (7.8%) were lost to follow-up. The overall complete abortion rate was 94.0%. Fourteen subjects required vacuum aspiration, nine of them prior to the scheduled follow-up and five thereafter. None of the pregnancies were ongoing. A decrease of 99% in s-hCG levels was noted in 99% of the women, when levels determined prior to mifepristone intake and those measured 15-71 days post-abortion were compared. CONCLUSION: This study confirms that s-hCG levels drop sharply after medical abortion. To assess the completeness of medical abortion, we recommend that clinical examination to be combined with determination of s-hCG. Ultrasonography should be carried out only when indicated. PMID- 17853165 TI - The effects of temperament and character on the choice of contraceptive methods. AB - OBJECTIVES: To identify the effects of temperament and character on the selection of contraceptive methods. METHODS: Cross-sectional study carried out in June 2005 at the Ondokuz Mayis University Samsun Health College with the participation of 102 young women. The participants were asked to complete the Contraception Choice Questionnaire devised by the researchers, and the Cloninger Temperament and Character Inventory. RESULTS: The mean age of the participants was 22.30 +/- 1.27 years; 39 participants (38.2%) mentioned Norplant, 30 (29.4%) condoms, 17 (16.6%) intrauterine devices (IUDs) and 16 (15.7%) oral contraceptives (OCs) as the method they would consider using in the future. The mean scores of self directedness and self-transcendence of the groups differed significantly (p < 0.05). Students who indicated they would choose OCs had higher average scores for self-directedness than those choosing IUDs; the mean self-transcendence scores of students choosing IUDs were significantly higher than the scores of those selecting condoms (p < 0.01). Subjects choosing Norplant cited ease of use; those choosing condoms cited their eliciting fewer side effects; those choosing IUDs cited their high levels of safety; and those choosing OCs cited ease of use and high reliability as the reasons for their choices. CONCLUSIONS: We think that identifying the roles of temperament and character in the selection process of a contraceptive method will help in achieving a wider application of contraception. PMID- 17853166 TI - Contraceptive efficacy and side effects of Implanon. AB - OBJECTIVE: To determine the efficacy and side effects of Implanon used for long term contraception. MATERIAL AND METHOD: Prospective study of 80 patients who used Implanon for long-term contraception between January 2004 and January 2006. Side effects, efficacy and removals were recorded. RESULTS: Amenorrhoea, infrequent bleeding and frequent bleeding were reported by 33 (41.25%), 19 (23.75%) and 14 patients (17.5%), respectively. Non-menstrual side effects comprised breast tenderness in 15 patients (18.75%), acne in eight (10%), headache and dizziness in three (3.75%); depressive mood disorders, pelvic pain and loss of libido were mentioned each by two of the women (2.5%). During the study period, Implanon was removed from 20 participants. No problem was encountered during its placement or removal. CONCLUSION: Patients considering use of Implanon must be carefully selected and informed about its expected side effects before placement. PMID- 17853167 TI - Actual use of the lactational amenorrhoea method. AB - OBJECTIVE: The lactational amenorrhoea method (LAM) is an effective contraceptive option in developing countries. Post-partum, of the women who accept to apply LAM, many never do. Our aim was to determine the actual use of LAM. METHODS: A group of 326 post-partum women who accepted LAM use were recruited. After 6 months, they were asked if they actually had applied the method or not. In a logistic regression analysis, nine socio-demographic and clinical variables were studied as predictors of actual LAM use. An alpha level was set at 0.05. RESULTS: Overall, of the 326 women, only 61 (18.7%) actually applied LAM. The mean duration of LAM use was 4.3 +/- 0.2 months. The main reason for not applying LAM was that women thought the method was ineffective (66.0%). The variable time of menses resumption emerged as a predictor of LAM use (p = 0.001). CONCLUSIONS: Despite post-partum acceptance, most women did not actually apply LAM. In our setting as well as in other developing countries, regular contacts with a health care provider could improve LAM use. PMID- 17853168 TI - Acceptability of the diaphragm in Mombasa Kenya: a 6-month prospective study. AB - OBJECTIVES: If proven acceptable, safe and effective, the diaphragm could be used as a female-controlled method of preventing both sexually-transmitted infections (STIs) and pregnancy. This study's aim was to assess the acceptability and safety of the diaphragm among sexually-active women in Mombasa, Kenya. METHODS: We conducted a 6-month prospective study among female sex workers (FSWs), and women attending sexual and reproductive health services. Diaphragm acceptability was assessed using continuation rates and factors associated with acceptability. Safety evaluations included colposcopy findings and incidence of urinary tract infections (UTIs) and STIs. RESULTS: Half the 185 participants were FSWs who had less schooling and were less likely to be married than other women. After 6 months, 55% (56/102) of sexually-active women reported having used the diaphragm each sex act during the preceding month. Women liked using the diaphragm (95%, 104/109), and 96% (125/130) reported willingness to continue using it. Colposcopy did not reveal significantly more vaginal or cervical lesions. Use of the diaphragm was not associated with an increase in bacterial vaginosis or UTIs. A pregnancy rate of 12 per 100 women/years was observed. CONCLUSION: After 6 months of diaphragm use in this setting, continuation rates were sustained, user satisfaction was high and adverse effects were few. PMID- 17853169 TI - Emergency surgical procedure for failed methotrexate treatment of cervical pregnancy: a case report. AB - Cervical pregnancy (CP) is a rare and dangerous condition, which may cause a massive haemorrhage. Ultrasonographic diagnosis consists of the visualization of the gestational sac and trophoblastic invasion in an endocervical localization. CP treatment modalities include dilatation and curettage (D&C) usually followed by intracervical tamponade, cervicotomy, angiographic embolization, ligation of the uterine arteries, and chemotherapy with methotrexate (MTX). MTX administration is a very appealing therapeutic modality of CP in the first trimester because of its convenience and efficacy. We report a case of unsuccessful treatment of a CP with systemic MTX administration, which led to an emergency surgical procedure for a sudden massive vaginal haemorrhage. A vaginal ligation of the cervical branches of the uterine arteries was carried out, followed by suction curettage, D&C and insertion of an intrauterine sterile tampon that was removed after 48 hours. The patient did not require a blood transfusion. Histological examination of the specimen confirmed the CP. PMID- 17853170 TI - How does a Belgian health care provider deal with a request for emergency contraception? AB - OBJECTIVE: To evaluate how Belgian health care providers deal with a request for emergency contraception. METHOD: In 2002-2003 we conducted 12 focus groups with pharmacists, general practitioners and school physicians. A skilled moderator accompanied by an observer conducted the focus groups using a semi-structured screenplay. RESULTS: All these health care providers agree with the free access to emergency contraception (EC), but experience considerable frustration with regard to the practical aspects and the legal framework. General practitioners (GPs) claim to spend a lot of time on requests for EC and they are concerned about the quality of the counselling provided in pharmacies. Pharmacists are creative when giving counselling in the pharmacy, but there is, nevertheless, a problem with a lack of privacy. School physicians are frustrated that there is no legal possibility to respond to a request for EC when they feel they are ideally placed to advise adolescents. CONCLUSION: The over-the-counter sale of EC offers women better access, but many barriers still interfere with optimal care. Pharmacists experience a lack of skills to communicate with adolescents and a lack of privacy to give counselling. GPs have good intentions, but are confronted with a lack of willingness on the part of the patients and also financial barriers. School physicians want more possibilities to help adolescents. PMID- 17853171 TI - State and trait anxiety levels of childless women in Kayseri, Turkey. AB - OBJECTIVES: To determine the prevalence rate of primary infertility in the provincial centre of Kayseri, the state-trait anxiety levels of childless women and the impact of some factors on the anxiety levels. MATERIALS AND METHODS: The investigation was carried out in the Kayseri province of Turkey. A sample group of 2400 married women aged 15-49 was visited at home and couples with primary infertility were identified. The female partners of these couples were included in the study group and were called 'childless women'. A control group was made up of women, with at least one child, who were of similar ages and resided in similar conditions as the study group. The State-Trait Anxiety Inventory was applied to the study group of 150 childless women, and the age and residence matched control group. RESULTS: The prevalence of primary infertility in the area was found to be 6.3%. Of the childless women, 89.3% had consulted a physician for diagnosis or treatment of infertility and 66.6% had applied traditional remedies in order to conceive. State anxiety scores had mean values of 43.3 and 31.4 in the study and control groups, respectively. The trait anxiety scores were higher with values of 49.5 and 45.1, respectively. The impact of childlessness on the state and trait anxiety levels was statistically significant. The duration of marriage was a significant predictor of the trait anxiety score. The impact of the educational level of the women and that of the husband's support on the trait anxiety score were also found to be statistically significant. CONCLUSION: The state and trait anxiety scores among childless women were higher than in controls. The trait anxiety scores among childless women increased with the duration of their marriage. The educational level of the childless women and the husband's support may affect anxiety levels. PMID- 17853172 TI - Determinants of healthcare utilization in Greece: implications for decision making. AB - OBJECTIVE: To explore factors influencing the utilization of primary and secondary healthcare in Greece. METHODS: A national, geographically stratified sample was randomly selected. From November 2001 to March 2002, 5000 questionnaires were mailed, 4427 were actually received, and 1819 were completed and returned (response rate 41%). The questionnaire investigated respondents' characteristics and their health services utilization. A number of potential utilization determinants were explored, such as region, gender, age, education, income, insurance coverage, number of family members, self-rated health status, country of birth, and parents' country of birth. RESULTS: The utilization of primary healthcare services depended on self-rated health status, age, income, gender, and region. Individuals with moderate and poor self-rated health, older people, women, and residents of the region of Epirus showed increased utilization of primary healthcare services. Income was a factor affecting the utilization of primary healthcare only at lower income levels. The frequency of visits for primary healthcare was negatively correlated with self-rated health status and increased as self-evaluation of health status worsened. Hospitalization was associated with self-rated health and insurance coverage for primary healthcare. Individuals with better self-rated health status, as well as those who were covered by health insurance for primary care, showed decreased hospital care utilization. The frequency of hospitalization depended on region and lower evaluations of health status. CONCLUSION: The findings of our research are encouraging, since they suggest that the utilization of health services in Greece is mostly determined by health status rather than other socioeconomic factors. It is believed that similar studies should be conducted in the country, since they can improve health service planning and reinforce decision-making towards healthcare resource allocation according to healthcare needs. PMID- 17853173 TI - Relationship between general practitioners and specialists in Morocco. PMID- 17853174 TI - What are the recommended guidelines for checking vitamin B12 by primary practitioners? PMID- 17853175 TI - Diagnosis of peritonsillar abscess in primary care. PMID- 17853176 TI - Formal quality criteria for websites do not guarantee complete health information of good quality: we need more attention to information on prognosis. PMID- 17853177 TI - Home visits by family physicians in Poland: a patient perspective. PMID- 17853178 TI - Cigarette smoking and adherence to antihypertensive medication in patients from primary care. PMID- 17853179 TI - General practitioners' management of influenza with or without neuraminidase inhibitors. PMID- 17853180 TI - Chilblains from the patient's perspective. PMID- 17853182 TI - The prognosis of joint pain in the older patient: general practitioners' views on discussing and estimating prognosis. PMID- 17853181 TI - Management of risk of glucocorticoid-induced osteoporosis due to systemic administration in general practice in Denmark. PMID- 17853183 TI - Industrial air pollution and children's respiratory health: a natural experiment in Calarasi. AB - BACKGROUND: In 1993-1997, we described a high incidence of wheezing in children living near the iron, steel, and coke factory of Calarasi (Romania). In 1998, the factory was closed. OBJECTIVE: To investigate the influence of closing the factory on the incidence of wheezing in children living near the factory. METHODS: We used this natural experiment to compare wheezing occurrence in children below age 2 in an area near the factory and in a village 10 km from the factory (Roseti). We studied three birth cohorts: those 2 years old before the closing of the factory (group 1), those born before the closing and returning 2 after the closing (group 2), those born after the closing (group 3). RESULTS: The relative risk (95% CI) of having at least one episode of wheezing during the first life-year was 0.51 (0.30-0.85) in group 3 versus group 1, and 0.95 (0.64 1.40) for group 2 versus group 1. After adjusting for possible confounders, the incidence dropped in Calarasi (odds ratio [OR] 0.38, 95% CI 0.19-0.76), while it increased in Roseti (OR 8.36, 95% CI 1.84-38.0). Results for the 2-year incidence were similar. CONCLUSION: Industrial air pollution by the factory was the main risk factor for wheezing during the first life-years of the children of Calarasi. Closing the factory resulted in a significant decrease in wheezing incidence rates, which still remained higher than in a nearby village. PMID- 17853185 TI - Activated protein C resistance in cord blood from healthy and complicated newborns. AB - OBJECTIVES: Newborns are susceptible to thrombosis secondary to the immature hemostatic system and maternal and fetal complications. The contribution of activated protein C resistance (APCR) to thrombosis tendency has not yet been established. This study was conducted to investigate the effects of maternal and fetal complications on APCR levels. METHODS: APCR levels were determined in cord blood from healthy term infants and compared with those in healthy preterm and complicated neonates as well as that in adult venous blood. RESULTS: The mean value of APCR in cord blood from healthy term infants (166 +/- 40 s) was not significantly different from that in adult venous blood (173 +/- 40 s). No significant differences in the mean cord blood APCR values were observed between healthy term and preterm infants, infants with vaginal and cesarean delivery, infants from preeclamptic and non-eclamptic mothers, and infants with or without perinatal asphyxia. The activity levels of protein C, protein S, and antithrombin III were not significantly different between these groups except for lower levels in preterm babies. CONCLUSIONS: The level of APCR in cord blood is comparable to that in adults and not influenced by maternal and fetal complications. It appears that APCR does not contribute to the thrombotic tendency in newborns. PMID- 17853184 TI - Maternal serum soluble CD30 is increased in pregnancies complicated with acute pyelonephritis. AB - OBJECTIVES: Normal pregnancy is characterized by activation of the innate immunity and suppression of the adaptive limb of the immune response. However, pregnant women are more susceptible to the effects of infection and microbial products than non-pregnant women. CD30 is a member of the tumor necrosis factor receptor superfamily and is preferentially expressed by activated T cells producing Th2-type cytokines. Its soluble form (sCD30) is proposed to be an index of Th2 immune response. High serum concentrations of sCD30 have been found in the acute phase of viral infections, such as HIV-1 and hepatitis B. There is, however, conflicting evidence about serum sCD30 concentration in patients with bacterial infections. The objective of this study was to determine whether there are changes in the serum concentration of sCD30 in pregnant women with pyelonephritis. METHODS: This cross-sectional study included normal pregnant women (N = 89) and pregnant women with pyelonephritis (N = 41). Maternal serum concentration of sCD30 was measured by a specific and sensitive enzyme-linked immunoassay. Non-parametric tests were used for comparisons. A p value <0.05 was considered statistically significant. RESULTS: (1) Pregnant women with pyelonephritis had a significantly higher median serum concentration of sCD30 than those with a normal pregnancy (median 44.3 U/mL, range 16-352.5 vs. median 29.7 U/mL, range 12.2-313.2, respectively; p < 0.001), and (2) No significant differences were found in the median maternal serum concentration of sCD30 between pregnant women with pyelonephritis who had a positive blood culture compared to those with a negative blood culture (median 47.7 U/mL, range 17.1 118.8 vs. median 42.6 U/mL, range 16-352.5, respectively; p = 0.86). CONCLUSIONS: Acute pyelonephritis during pregnancy is associated with a higher maternal serum concentration of sCD30 than normal pregnancy. This finding is novel and suggests that pregnant women with pyelonephritis may have a complex immune state in which there is activation of some components of what is considered a Th2 immune response. PMID- 17853186 TI - Factors that influence the timing of spontaneous labor at term. AB - OBJECTIVE: Whether pre-term birth culminates as a result of a de novo pathologic process or is more simply early activation of physiologic mechanisms is unknown. Exploration of the onset of labor in term women with classical risk factors for early delivery might provide insights into the mechanisms leading to pre-term birth. This study examines whether sociodemographic factors known to increase the risk of pre-term birth also affect the length of term gestations. METHODS: From a large prospective cohort composed of women delivering from 1995-2000, a sample was selected of 441 women from Central North Carolina, US, who delivered singletons after 37 weeks gestation. An algorithm was designed to identify induced labors and gestational age was censored at the time of induction. Gestational age was assigned by sonography and menstrual dating. Data were analysed using the Cox proportional hazards model. The main outcome measure was time to spontaneous labor. RESULTS: Women with 12 years of education had longer periods of gestation than women with less than 12 years of education, HR = 0.57 [0.39, 0.84]. Shorter gestational periods were found for women with pre-term premature rupture of membranes (PPROM) in a previous pregnancy, HR = 3.70 [1.60, 8.52], even after adjusting for confounders. Smoking was not associated (p > 0.1) with the timing of labor at term. CONCLUSIONS: By studying the timing of spontaneous parturition at term we identified that there is little overlap in risk factors that affect timing of delivery between spontaneous term and pre-term births. PMID- 17853187 TI - Murine aortic reactivity is programmed equally by maternal low protein diet or late gestation dexamethasone. AB - OBJECTIVE: In rats, maternal low protein diet induces growth restriction, increases fetal glucocorticoid exposure and programs cardiovascular and endocrine dysfunction in adult offspring. We hypothesized that both maternal low protein diet and late gestation dexamethasone program murine offspring to develop hypertension, vascular dysfunction, and glucose intolerance. METHODS: An iso caloric low protein diet (LP) was provided to dams from E0 to E19. Additional dams received a normal protein diet without (NP) or with either dexamethasone (NP Dex, 0.1 mg/kg/d sc) or normal saline (NP-NS) from E10 to E18. RESULTS: Offspring of dams given LP weighed less at 10 days than NP offspring, while Dex administration did not alter pup weight. At 4 months, all four groups had similar systolic blood pressures and no detectable differences were evoked by oral L NAME. Offspring of LP mice had impaired glucose clearance that was directly correlated with their weight at 10 days. Aortic rings from offspring of both LP and NP-Dex exposed dams had impaired vasodilatation to acetylcholine. CONCLUSIONS: These findings demonstrate that both maternal low protein diet and late gestation dexamethasone program murine offspring to develop endothelial dysfunction in the absence of hypertension, while only maternal LP impaired perinatal growth and glucose clearance in adult offspring. KEYWORDS: Acetylcholine; blood pressure; developmental biology; fetal programming PMID- 17853190 TI - Spatial exploration patterns determine navigation efficiency: trade-off between memory demands and distance travelled. AB - A total of 41 participants explored a novel square-shaped environment containing five identical boxes each hiding a visually distinct object. After an initial free exploration the participants were required to locate the objects first in a predetermined and subsequently in an optional order task. Two distinct exploration strategies emerged: Participants explored either along the main axes of the room (axial), or in a more spatially spread, circular pattern around the edges of the room (circular). These initial exploration strategies influenced the optimality of spatial navigation performance in the subsequent optional order task. The results reflect a trade-off between memory demands and distance efficiency. The more sequential axial strategy resulted in fewer demands on spatial memory but required more distance to be travelled. The circular strategy was more demanding on memory but required less subsequent travelling distance. The findings are discussed in terms of spatial knowledge acquisition and optimality of strategy representations. PMID- 17853191 TI - Blocking of human causal learning involves learned changes in stimulus processing. AB - Several theories of associative learning propose that blocking reflects changes in the processing devoted to learning about cues. The results of the only direct test of this suggestion in human learning (Kruschke & Blair, 2000) could equally well be explained in terms of, among others, interference in learning or memory. The present study tested this suggestion in a situation in which processing change and interference accounts predict opposing results. Results support the idea that blocking in human learning can reflect a change in processing of the cues involved. PMID- 17853192 TI - Knowing when to hear aids what to hear. AB - Temporal preparation often has been assumed to influence motor stages of information processing. Recent studies, however, challenge this notion and provide evidence for a facilitation of visual processing. The present study was designed to investigate whether perceptual processing in the auditory domain also benefits from temporal preparation. To this end, we employed a pitch discrimination task. In Experiment 1, discrimination performance was clearly improved when participants were temporally prepared. This finding was confirmed in Experiment 2, which ruled out possible influences of short-term memory. The results support the notion that temporal preparation enhances perceptual processing not only in the visual, but also in the auditory, modality. PMID- 17853188 TI - Maternal serum soluble CD30 is increased in normal pregnancy, but decreased in preeclampsia and small for gestational age pregnancies. AB - OBJECTIVE: Women with preeclampsia and those who deliver small for gestational age (SGA) neonates are characterized by intravascular inflammation (T helper 1 (Th1)-biased immune response). There is controversy about the T helper 2 (Th2) response in preeclampsia and SGA. CD30, a member of the tumor necrosis factor receptor superfamily, is preferentially expressed in vitro and in vivo by activated T cells producing Th2-type cytokines. Its soluble form (sCD30) has been proposed to be an index of Th2 immune response. The objective of this study was to determine whether the maternal serum concentration of sCD30 changes with normal pregnancy, as well as in mothers with preeclampsia and those who deliver SGA neonates. METHODS: This cross-sectional study included patients in the following groups: (1) non-pregnant women (N = 49); (2) patients with a normal pregnancy (N = 89); (3) patients with preeclampsia (N = 100); and (4) patients who delivered an SGA neonate (N = 78). Maternal serum concentration of sCD30 was measured by a specific and sensitive enzyme-linked immunoassay. Non-parametric tests with post-hoc analysis were used for comparisons. A p value <0.05 was considered statistically significant. RESULTS: (1) The median sCD30 serum concentration of pregnant women was significantly higher than that of non pregnant women (median 29.7 U/mL, range 12.2-313.2 vs. median 23.2 U/mL, range 14.6-195.1, respectively; p = 0.01). (2) Patients with preeclampsia had a significantly lower median serum concentration of sCD30 than normal pregnant women (median 24.7 U/mL, range 7.6-71.2 vs. median 29.7 U/mL, range 12.2-313.2, respectively; p < 0.05). (3) Mothers with SGA neonates had a lower median concentration of sCD30 than normal pregnant women (median 23.4 U/mL, range 7.1 105.3 vs. median 29.7 U/mL, range 12.2-313.2, respectively; p < 0.05). (4) There was no significant correlation (r = -0.059, p = 0.5) between maternal serum sCD30 concentration and gestational age (19-38 weeks) in normal pregnant women. CONCLUSIONS: (1) Patients with preeclampsia and those who deliver an SGA neonate had a significantly lower serum concentration of sCD30 than normal pregnant women. (2) This finding is consistent with the view that preeclampsia and SGA are associated with a polarized Th1 immune response and, perhaps, a reduced Th2 response. PMID- 17853194 TI - Slowing down an internal clock: implications for accounts of performance on four timing tasks. AB - An experiment investigated the potential effects of lowering arousal on performance on time perception tasks. Four participant groups received different tasks: Normal and episodic temporal generalization, bisection, and verbal estimation, all involving judgements of the duration of visual stimuli. Self rated arousal during the experimental session was lowered by spacing experimental trials approximately 10 s apart. Between the early and late blocks of the experiment, performance changed on normal temporal generalization and verbal estimation, but not on episodic temporal generalization and bisection. The changes were consistent with the idea that the pacemaker of the participant's internal clock had been slowed down by the slow trial spacing. Results suggested that bisection was based on a criterion that adjusted during the experiment, whereas verbal estimation was based on preexisting standards, or those established early in the experiment. PMID- 17853195 TI - Influences on the first-perspective alignment effect from text route descriptions. AB - Four experiments investigated the more efficient recall of routes learned from text descriptions when the imagined orientation at test was in alignment with the first experienced perspective. Experiments 1 and 2 replicated the effect, but found little evidence for the influence of an external frame of reference provided either by describing a salient landmark external to the route, or by employing cardinal directions in the descriptions. In Experiment 3, the first perspective alignment (FPA) effect was relatively unaffected by elaboration of spatial information or more experience of reading the text. Experiment 4 found attenuation of the FPA effect when participants made active spatial judgements from imagined key locations while learning. The results are discussed in relation to theories of spatial reference frames and the influence of location salience. PMID- 17853197 TI - Previous attentional set can induce an attentional blink with task-irrelevant initial targets. AB - Identification of a second target is often impaired by the requirement to process a prior target in a rapid serial visual presentation (RSVP). This is termed the attentional blink. Even when the first target is task irrelevant an attentional blink may occur providing this first target shares similar features with the second target (contingent capture). An RSVP experiment was undertaken to assess whether this first target can still cause an attentional blink when it did not require a response and did not share any features with the following target. The results revealed that such task-irrelevant targets can induce an attentional blink providing that they were task relevant on a previous block of trials. This suggests that irrelevant focal stimuli can distract attention on the basis of a previous attentional set. PMID- 17853198 TI - Effects of head orientation on gaze perception: how positive congruency effects can be reversed. AB - Several past studies have considered how perceived head orientation may be combined with perceived gaze direction in judging where someone else is attending. In three experiments we tested the impact of different sources of information by examining the role of head orientation in gaze-direction judgements when presenting: (a) the whole face; (b) the face with the nose masked; (c) just the eye region, removing all other head-orientation cues apart from some visible part of the nose; or (d) just the eyes, with all parts of the nose masked and no head orientation cues present other than those within the eyes themselves. We also varied time pressure on gaze direction judgements. The results showed that gaze judgements were not solely driven by the eye region. Gaze perception can also be affected by parts of the head and face, but in a manner that depends on the time constraints for gaze direction judgements. While "positive" congruency effects were found with time pressure (i.e., faster left/right judgements of seen gaze when the seen head deviated towards the same side as that gaze), the opposite applied without time pressure. PMID- 17853200 TI - Competition during the processing of quantifier scope ambiguities: evidence from eye movements during reading. AB - We investigated the processing of sentences containing a quantifier scope ambiguity, such as Kelly showed a photo to each critic, which is ambiguous between the indefinite phrase (a photo) having one or many referents. Ambiguity resolution requires the computation of relative quantifier scope, with either a photo or each critic taking wide scope, thereby determining the number of referents. Using eye tracking, we established that multiple factors, including the grammatical function and surface linear order of quantified phrases, along with their lexical characteristics, interact during the processing of relative quantifier scope, with conflict between factors incurring a processing cost. We discuss the results in terms of theoretical accounts attributing sentence processing difficulty to either reanalysis (e.g., Fodor, 1982) or competition between rival analyses (e.g., Kurtzman & MacDonald, 1993). PMID- 17853201 TI - Implicit learning of second-, third-, and fourth-order adjacent and nonadjacent sequential dependencies. AB - Serial reaction time (SRT) task studies have established that people can implicitly learn first- and second-order adjacent dependencies. Sequential confounds have made it impossible to draw conclusions regarding learning of nonadjacent dependencies and learning of third- and fourth-order adjacent dependencies. Addressing the confounds, the present study shows that people can implicitly learn second-, third-, and fourth-order adjacent and nonadjacent dependencies embedded in probabilistic sequences of target locations. PMID- 17853202 TI - Mislocated fixations can account for parafoveal-on-foveal effects in eye movements during reading. AB - Contrasting predictions of serial and parallel views on the processing of foveal and parafoveal information during reading were tested. A high-frequency adjective (young) was followed by either a high-frequency word(n) (child) or a low frequency word(n) (tenor), which in turn was followed by either a correct (performing) or an orthographic illegal word(n+1) (pxvforming) as a parafoveal preview. A limited parafoveal-on-foveal effect was observed: There were inflated fixation times on word(n) when the preview of word(n+1) was orthographically illegal. However, this parafoveal-on-foveal effect was (a) independent of the frequency of word(n), (b) restricted to those instances when the eyes were very close to word(n+1), and (c) associated with relatively long prior saccades. These observations are all compatible with a mislocated fixation account in which parafoveal-on-foveal effects result from saccadic undershoots of word(n+1) and with a serial model of eye movement control during reading. PMID- 17853203 TI - Concreteness effects in different tasks: implications for models of short-term memory. AB - This study investigates concreteness effects in tasks requiring short-term retention. Concreteness effects were assessed in serial recall, matching span, order reconstruction, and free recall. Each task was carried out both in a control condition and under articulatory suppression. Our results show no dissociation between tasks that do and do not require spoken output. This argues against the redintegration hypothesis according to which lexical-semantic effects in short-term memory arise only at the point of production. In contrast, concreteness effects were modulated by task demands that stressed retention of item versus order information. Concreteness effects were stronger in free recall than in serial recall. Suppression, which weakens phonological representations, enhanced the concreteness effect with item scoring. In a matching task, positive effects of concreteness occurred with open sets but not with closed sets of words. Finally, concreteness effects reversed when the task asked only for recall of word positions (as in the matching task), when phonological representations were weak (because of suppression), and when lexical semantic representations overactivated (because of closed sets). We interpret these results as consistent with a model where phonological representations are crucial for the retention of order, while lexical-semantic representations support maintenance of item identity in both input and output buffers. PMID- 17853204 TI - Phonological similarity and lexicality effects in children's verbal short-term memory: concerns about the interpretation of probed recall data. AB - Probed recall tasks are often used to assess aspects of children's verbal short term memory development because they are not subject to potentially confounding output effects. However, the marked recency effects that are observed in probed recall means that these tasks are potentially insensitive to experimental manipulations when later serial positions are probed. This clouds the interpretation of data from probed recall studies in which children of different ages are presented with to-be-remembered lists of different lengths. In two experiments we examined the magnitude of phonological similarity and lexicality effects in both 5- to 6- and 8- to 9-year-old children. In each case performance on probed recall tasks was contrasted with that seen on tests of serial recognition. The results indicated that probed recall tasks are potentially less sensitive to experimental manipulations in younger than older children. However, comparable effects of both phonological similarity and lexicality were seen in both age groups using serial recognition procedures. These findings have implications for the interpretation of other studies that have examined the development of verbal short-term memory using probed recall and for theoretical accounts of the development of phonological similarity and lexicality effects in children. PMID- 17853205 TI - The SNARC effect in the processing of second-language number words: further evidence for strong lexico-semantic connections. AB - We present new evidence that word translation involves semantic mediation. It has been shown that participants react faster to small numbers with their left hand and to large numbers with their right hand. This SNARC (spatial-numerical association of response codes) effect is due to the fact that in Western cultures the semantic number line is oriented from left (small) to right (large). We obtained a SNARC effect when participants had to indicate the parity of second language (L2) number words, but not when they had to indicate whether L2 number words contained a particular sound. Crucially, the SNARC effect was also obtained in a translation verification task, indicating that this task involved the activation of number magnitude. PMID- 17853209 TI - Multimodal discrimination learning in humans: evidence for configural theory. AB - Human contingency learning was used to compare the predictions of configural and elemental theories. In three experiments, participants were required to learn which indicators were associated with an increase in core temperature of a fictitious nuclear plant. Experiments 1 and 2 investigated the rate at which a triple-element stimulus (ABC) could be discriminated from either single-element stimuli (A, B, and C) or double-element stimuli (AB, BC, and AC). Experiment 1 used visual stimuli, whilst Experiment 2 used visual, auditory, and tactile stimuli. In both experiments the participants took longer to discriminate the triple-element stimulus from the more similar double-element stimuli than from the less similar single-element stimuli. Experiment 3 tested for summation with stimuli from either a single or multiple modalities, and summation was found only in the latter case. Thus, the pattern of results seen in Experiments 1 and 2 was not dependent on whether the stimuli were single modal or multimodal, nor was it dependent on whether the stimuli could elicit summation. This pattern of results is consistent with predictions derived from Pearce's (1987, 1994) configural theory. PMID- 17853210 TI - Locating targets from imagined perspectives: comparing labelling with pointing responses. AB - Participants in two experiments adopted imagined perspectives in a perceptually available spatial scene and located targets by using either verbal terms (labelling) or arrows (pointing). Results revealed that performance was faster and more accurate for labelling than for pointing and more so when the adopted perspectives were misaligned with the physical orientation of the participant. This finding was obtained even when an orientation cue allowed participants to adopt the imagined perspective in advance of target presentation. A third experiment replicated these findings using traditional pointing and verbal responding. We argue that performance from misaligned perspectives in perspective taking tasks suffers due to reference frame conflicts and that these conflicts are more pronounced with pointing and other manual responses that rely more on the reference frame of the physical body. PMID- 17853211 TI - Inhibitory sensory preconditioning detected with a sodium depletion procedure. AB - In each of two experiments, two groups of rats were exposed to three flavoured solutions: A (citric acid), B (salt), and AX (a compound of citric acid and saccharin). Both experiments used a between-subjects design in which a paired group received presentations of A followed by B, alternating with presentations of AX (i.e., A --> B/AX), and an unpaired group received alternating presentations of A, B, and AX (i.e., A/B/AX). This arrangement was expected to establish X as an inhibitor of B in group paired but not in group unpaired. In Experiment 1, after preexposure all subjects received a single presentation of an XB compound, then experienced sodium depletion, and were tested for their consumption of X, which was greater in group unpaired than in group paired. In Experiment 2, after preexposure, all subjects received four presentations of a new flavour, C, in compound with B and subsequently, under sodium depletion, were tested for consumption of XC. Intake of the XC compound was less in group paired than in group unpaired. These results suggest that, in group paired, X acquired an inhibitory relationship with B both retarding the acquisition of an excitatory association with B (retardation test, Experiment 1) and reducing the response to a new stimulus, C, strongly associated to B (summation test, Experiment 2). These results provide direct evidence of inhibition between two neutral stimuli and, therefore, of inhibitory sensory preconditioning. PMID- 17853212 TI - Emotional and neutral scenes in competition: orienting, efficiency, and identification. AB - To investigate preferential processing of emotional scenes competing for limited attentional resources with neutral scenes, prime pictures were presented briefly (450 ms), peripherally (5.2 degrees away from fixation), and simultaneously (one emotional and one neutral scene) versus singly. Primes were followed by a mask and a probe for recognition. Hit rate was higher for emotional than for neutral scenes in the dual- but not in the single-prime condition, and A' sensitivity decreased for neutral but not for emotional scenes in the dual-prime condition. This preferential processing involved both selective orienting and efficient encoding, as revealed, respectively, by a higher probability of first fixation on -and shorter saccade latencies to--emotional scenes and by shorter fixation time needed to accurately identify emotional scenes, in comparison with neutral scenes. PMID- 17853213 TI - Mirror reversal: empirical tests of competing accounts. AB - In a mirror, left and right are said to look reversed. Surprisingly, this very familiar phenomenon, mirror reversal, has still no agreed-upon account to date. This study compared a variety of accounts in the light of empirical data. In Experiment 1, 102 students judged whether the mirror image of a person or a character looked reversed or not in 15 settings and also judged the directional relation between its components. In Experiment 2, 52 students made the reversal judgements in 13 settings. It was found for the first time that a substantial proportion of people denied the left-right mirror reversal of a person, whereas virtually all of them did recognize that of a character. This discrepancy strongly suggested that these two kinds of mirror reversal are produced by different processes, respectively. A number of findings including this discrepancy clearly contradicted two accounts that are currently active: the one based on the priority of the up-down and front-back axes over the left-right axis, and the one based on the physical rotation of an object. All the findings were consistent with an account that considered mirror reversal a complex of three different phenomena produced by three different processes, respectively. PMID- 17853214 TI - The effect of word length in short-term memory: Is rehearsal necessary? AB - Three experiments investigated the effect of word length on a serial recognition task when rehearsal was prevented by a high presentation rate with no delay between study and test lists. Results showed that lists of short four-phoneme words were better recognized than lists of long six-phoneme words. Moreover, this effect was equivalent to that observed in conditions in which there was a delay between lists, thereby making rehearsal possible in the interval. These findings imply that rehearsal does not play a central role in the origin of the word length effect. An alternative explanation based on differences in the degree of retroactive interference generated by long and short words is proposed. PMID- 17853217 TI - Two modes of sensorimotor integration in intention-based and stimulus-based actions. AB - Human actions may be driven endogenously (to produce desired environmental effects) or exogenously (to accommodate to environmental demands). There is a large body of evidence indicating that these two kinds of action are controlled by different neural substrates. However, only little is known about what happens- in functional terms--on these different "routes to action". Ideomotor approaches claim that actions are selected with respect to their perceptual consequences. We report experiments that support the validity of the ideomotor principle and that, at the same time, show that it is subject to a far-reaching constraint: It holds for endogenously driven actions only! Our results suggest that the activity of the two "routes to action" is based on different types of learning: The activity of the system guiding stimulus-based actions is accompanied by stimulus-response (sensorimotor) learning, whereas the activity of the system controlling intention based actions results in action-effect (ideomotor) learning. PMID- 17853218 TI - Serial memory for sound-specified locations: effects of spatial uncertainty and motor suppression. AB - According to Parmentier and Jones (2000), serial recall of locations that are specified by a sequence of sounds is prone to temporal error and is unaffected by motor suppression during retention. Experiments are reported here that show that with increased spatial uncertainty at recall (Experiment 1) and presentation (Experiment 2), spatial rather than temporal errors predominate. This is also the case when serial recall of sound-specified locations is subject to interference from a motor suppression task (Experiment 3). Contrary to Parmentier and Jones's (2000) original report, these results suggest that the memory representation for location is not necessarily amodal but is influenced by the representational requirements of the task being performed. This is consistent with recent findings that provide evidence for a distinct spatial working memory. PMID- 17853219 TI - Directed forgetting in the list method affects recognition memory for source. AB - The effects of list-method directed forgetting on recognition memory were explored. In Experiment 1 (N = 40), observers were instructed to remember words and their type-cases; in Experiment 2 (N = 80), the instruction was to remember words and their colours. Two lists of 10 words were presented; after the first list, half of the observers (forget) were instructed to forget that list, and the other half (remember) were not given the forget instruction. Recognition of items (words) as well as source (encoding list + case/colour) was measured for forget and remember observers. The forget instruction affected case/colour memory more consistently than item and list memory, a multinomial analysis indicated that source information was affected by the forget instructions. The results indicated that recognition of source information may be a more sensitive indicator of forgetting than recognition of items. PMID- 17853220 TI - Facilitation and inhibition caused by the orienting of attention in propositional reasoning tasks. AB - In an attempt to study the orienting of attention in reasoning, we developed a set of propositional reasoning tasks structurally similar to Posner's (1980) spatial cueing paradigm, widely used to study the orienting of attention in perceptual tasks. We cued the representation in working memory of a reasoning premise, observing whether inferences drawn using that premise or a different, uncued one were facilitated, hindered, or unaffected. The results of Experiments 1a, 1b, 1c, and 1d, using semantically (1a-1c) or statistically (1d) informative cues, showed a robust, long-lasting facilitation for drawing inferences from the cued rule. In Experiment 2, using uninformative cues, inferences from the cued rule were facilitated with a short stimulus onset asynchrony (SOA), whereas they were delayed when the SOA was longer, an effect that is similar to the "inhibition of return" (IOR) in perceptual tasks. Experiment 3 used uninformative cues, three different SOAs, and inferential rules with disjunctive antecedents, replicating the IOR-like effect with the long SOAs and, at the short SOA, finding evidence of a gradient-like behaviour of the facilitation effect. Our findings show qualitative similarities to some effects typically observed in the orienting of visual attention, although the tasks did not involve spatial orienting. PMID- 17853221 TI - Nonlinear visuomotor transformations: locus and modularity. AB - Participants in two experiments moved a mouse-like device to the right to move a cursor on a computer screen to a target position. The cursor was invisible during motion but reappeared at the end of each movement. The relationship between the amplitudes of the cursor movement and the mouse movement was exponential in Experiment 1 and logarithmic in Experiment 2 for two groups of participants, while it was linear for the control groups in both experiments. The results of both experiments indicate that participants adjusted well to the external transformation by developing an internal model that approximated the inverse of the external transformation. We introduce a method to determine the locus of the internal model. It indicates that the internal model works at a processing level that either preceded specification of movement amplitude, or had become part of movement amplitude specification. Limited awareness of the nonlinear mouse-cursor relationship and the fact that a working-memory task had little effect on performance suggest that the internal model is modular and not dependent on high level cognitive processes. PMID- 17853222 TI - Subjective shortening with filled and unfilled auditory and visual intervals in humans? AB - Two experiments tested humans on a memory for duration task based on the method of Wearden and Ferrara (1993), which had previously provided evidence for subjective shortening in memory for stimulus duration. Auditory stimuli were tones (filled) or click-defined intervals (unfilled). Filled visual stimuli were either squares or lines, with the unfilled interval being the time between two line presentations. In Experiment 1, good evidence for subjective shortening was found when filled and unfilled visual stimuli, or filled auditory stimuli, were used, but evidence for subjective shortening with unfilled auditory stimuli was more ambiguous. Experiment 2 used a simplified variant of the Wearden and Ferrara task, and evidence for subjective shortening was obtained from all four stimulus types. PMID- 17853225 TI - The modulating influence of category size on the classification of exception patterns. AB - Generalization gradients to exception patterns and the category prototype were investigated in two experiments. In Experiment 1, participants first learned categories of large size that contained a single exception pattern, followed by a transfer test containing new instances that had a manipulated similarity relationship to the exception or a nonexception training pattern as well as distortions of the prototype. The results demonstrated transfer gradients tracked the prototype category rather than the feedback category of the exception category. In Experiment 2, transfer performance was investigated for categories varying in size (5, 10, 20), partially crossed with the number of exception patterns (1, 2, 4). Here, the generalization gradients tracked the feedback category of the training instance when category size was small but tracked the prototype category when category size was large. The benefits of increased category size still emerged, even with proportionality of exception patterns held constant. These, and other outcomes, were consistent with a mixed model of classification, in which exemplar influences were dominant with small-sized categories and/or high error rates, and prototype influences were dominant with larger sized categories. PMID- 17853227 TI - Predicting semantic priming at the item level. AB - The current study explores a set of variables that have the potential to predict semantic priming effects for 300 prime-target associates at the item level. Young and older adults performed either lexical decision (LDT) or naming tasks. A multiple regression procedure was used to predict priming based upon prime characteristics, target characteristics, and prime-target semantic similarity. Results indicate that semantic priming (a) can be reliably predicted at an item level; (b) is equivalent in magnitude across standardized measures of priming in LDTs and naming tasks; (c) is greater following quickly recognized primes; (d) is greater in LDTs for targets that produce slow lexical decision latencies; (e) is greater for pairs high in forward associative strength across tasks and across stimulus onset asynchronies (SOAs); (f) is greater for pairs high in backward associative strength in both tasks, but only at a long SOA; and (g) does not vary as a function of estimates from latent semantic analysis (LSA). Based upon these results, it is suggested that researchers take extreme caution in comparing priming effects across different item sets. Moreover, the current findings lend support to spreading activation and feature overlap theories of priming, but do not support priming based upon contextual similarity as captured by LSA. PMID- 17853228 TI - Shallow processing of ambiguous pronouns: evidence for delay. AB - Two self-paced reading-time experiments examined how ambiguous pronouns are interpreted under conditions that encourage shallow processing. In Experiment 1 we show that sentences containing ambiguous pronouns are processed at the same speed as those containing unambiguous pronouns under shallow processing, but more slowly under deep processing. We outline three possible models to account for the shallow processing of ambiguous pronouns. Two involve an initial commitment followed by possible revision, and the other involves a delay in interpretation. In Experiment 2 we provide evidence that supports the delayed model of ambiguous pronoun resolution under shallow processing. We found no evidence to support a processing system that makes an initial commitment to an interpretation of the pronoun when it is encountered. We extend the account of pronoun resolution proposed by Rigalleau, Caplan, and Baudiffier (2004) to include the treatment of ambiguous pronouns under shallow processing. PMID- 17853229 TI - On some limits of hypothetical thinking. AB - Faced with extreme demands, hypothetical thinking runs the danger of total failure. Paradoxical propositions such as the Liar ("I am lying") provide an opportunity to test it to its limits, while the Liar's nonparadoxical counterpart, the Truthteller ("I am telling the truth"), provides a useful comparison. Two experiments are reported, one with abstract materials ("If I am a knave then I live in Emerald City") and one with belief-laden materials (a judge says: "If I am a knave then I enjoy pop music"). In both experiments, conditionals with Truthteller-type antecedents were "collapsed" to responses of conditional probability closely resembling estimates of control items. Liar-type antecedents, in contrast, dramatically weakened belief in conditionals in which they were embedded. The results are discussed in the framework of the theory of hypothetical thinking. PMID- 17853230 TI - A mixed Rasch model of dual-process conditional reasoning. AB - A fine-grained dual-process approach to conditional reasoning is advocated: Responses to conditional syllogisms are reached through the operation of either one of two systems, each of which can rely on two different mechanisms. System1 relies either on pragmatic implicatures or on the retrieval of information from semantic memory; System2 operates first through inhibition of System1, then (but not always) through activation of analytical processes. It follows that reasoners will fall into one of four groups of increasing reasoning ability, each group being uniquely characterized by (a) the modal pattern of individual answers to blocks of affirming the consequent (AC), denying the antecedent (DA), and modus tollens (MT) syllogisms featuring the same conditional; and (b) the average rate of determinate answers to AC, DA, and MT. This account receives indirect support from the extant literature and direct support from a mixed Rasch model of responses given to 18 syllogisms by 486 adult reasoners. PMID- 17853231 TI - Investigating the influence of continuous babble on auditory short-term memory performance. AB - A number of factors could explain the adverse effect that babble noise has on memory for spoken words (Murphy, Craik, Li, & Schneider, 2000). Babble could degrade the perceptual representation of words to such an extent that it compromises their subsequent processing, or the presence of speech noise in the period between word presentations could interfere with rehearsal. Thirdly, the top-down processes needed to extract the words from the babble could draw on resources that otherwise would be used for encoding. We tested all these hypotheses by presenting babble either only during word presentation or rehearsal, or by gating the babble on and off 500 ms before and after each word pair. Only the last condition led to a decline in memory. We propose that this decline in memory occurred because participants were focusing their attention on the auditory stream (to enable them to better segregate the words from the noise background) rather than on remembering the words they had heard. To further support our claim we show that a similar memory deficit results when participants perform the same memory task in quiet together with a nonauditory attention demanding secondary task. PMID- 17853232 TI - Face familiarity, distinctiveness, and categorical perception. AB - Four experiments with faces support the original interpretation of categorical perception (CP) as only present for familiar categories. Unlike in the results of Levin and Beale (2000), no evidence is found for face identity CP with unfamiliar faces. Novel face identities were shown to be capable of encoding for immediate sorting purposes but the representations utilized do not have the format of perceptual categories. One possibility explored was that a choice of a distinctive face as an end-point in a morphed continuum can spuriously produce effects that resemble CP. Such morphed continua provided unequal psychological responses to equal physical steps though much more so in a better likeness paradigm than for forced-choice recognition. Thus, researchers doing almost the same experiments may produce very different results and come to radically different conclusions. PMID- 17853233 TI - Opposite aftereffects for Chinese and Caucasian faces are selective for social category information and not just physical face differences. AB - Opposite changes in perception (aftereffects) can be simultaneously induced for faces from different social categories--for example, Chinese and Caucasian faces. We investigated whether these aftereffects are generated in high-level face coding that is sensitive to the social category information in faces, or in earlier visual coding sensitive to simple physical differences between faces. We caricatured the race of face stimuli and created face continua ranging from caricatured Caucasian faces (SuperCaucasian) to caricatured Chinese faces (SuperChinese). Participants were adapted to oppositely distorted faces that were a fixed physical distance apart on the morph continua. Larger opposite aftereffects were found following adaptation to faces from different race categories (e.g., contracted Chinese and expanded Caucasian faces), than for faces that were the same physical distance apart on the morph continua, but were within a race category (e.g., contracted SuperChinese and expanded Chinese faces). These results suggest that opposite aftereffects for Chinese and Caucasian faces reflect the recalibration of face neurons tuned to high-level social category information. PMID- 17853235 TI - Children's and adults' processing of anomaly and implausibility during reading: evidence from eye movements. AB - The eye movements of 24 children and 24 adults were monitored to compare how they read sentences containing plausible, implausible, and anomalous thematic relations. In the implausible condition the incongruity occurred due to the incompatibility of two objects involved in the event denoted by the main verb. In the anomalous condition the direct object of the verb was not a possible verb argument. Adults exhibited immediate disruption with the anomalous sentences as compared to the implausible sentences as indexed by longer gaze durations on the target word. Children exhibited the same pattern of effects as adults as far as the anomalous sentences were concerned, but exhibited delayed effects of implausibility. These data indicate that while children and adults are alike in their basic thematic assignment processes during reading, children may be delayed in the efficiency with which they are able to integrate pragmatic and real-world knowledge into their discourse representation. PMID- 17853236 TI - An isolation effect in serial memory for spatial information. AB - This paper reports the first demonstration of an isolation effect or von Restorff effect (von Restorff, 1933) in the context of a spatial-memory task: Short-term serial recall was enhanced for both the location and the serial position of one red dot presented amongst a sequence of otherwise black dots. When the serial position of the isolate was fixed, the spatial isolation effect only emerged when participants received a control block of trials before the block of isolation trials (Experiment 1). However, when the serial position of the isolate was varied across isolation trials, an isolation effect was still produced regardless of condition order (Experiment 2). It is suggested that both temporal grouping strategies and greater item-specific processing may have contributed to the enhanced retention of the isolate. PMID- 17853237 TI - Action planning in sequential skills: relations to music performance. AB - The hypothesis that planning music-like sequential actions involves anticipating their auditory effects was investigated in a series of experiments. Participants with varying levels of musical experience responded to each of four colour-patch stimuli by producing a unique sequence of three taps on three vertically aligned keys. Each tap triggered a tone in most experimental conditions. Response--effect (key-to-tone) mapping was either compatible--taps on the top, middle, and bottom keys triggered high, medium, and low pitched tones, respectively--or incompatible -key-to-tone mapping was scrambled, reversed, or neutral (taps on different keys triggered the same tone). The results suggest that action planning was faster with compatible than with incompatible mappings (and faster than with no tones). Furthermore, the size of this compatibility effect grew with increasing musical experience, which suggests that improvements in auditory imagery ability that typically accompany musical training may augment the role of anticipatory auditory-effect representations during planning. PMID- 17853238 TI - Deficits in verbal long-term memory and learning in children with poor phonological short-term memory skills. AB - Possible links between phonological short-term memory and both longer term memory and learning in 8-year-old children were investigated in this study. Performance on a range of tests of long-term memory and learning was compared for a group of 16 children with poor phonological short-term memory skills and a comparison group of children of the same age with matched nonverbal reasoning abilities but memory scores in the average range. The low-phonological-memory group were impaired on longer term memory and learning tasks that taxed memory for arbitrary verbal material such as names and nonwords. However, the two groups performed at comparable levels on tasks requiring the retention of visuo-spatial information and of meaningful material and at carrying out prospective memory tasks in which the children were asked to carry out actions at a future point in time. The results are consistent with the view that poor short-term memory function impairs the longer-term retention and ease of learning of novel verbal material. PMID- 17853239 TI - Differential acquisition, extinction, and reinstatement of conditioned suppression in mice. AB - In animals, the reappearance of conditioned fear responses after extinction has been primarily investigated using single-cue conditioning paradigms. However, a differential paradigm can overcome several of the disadvantages associated with a single-cue procedure. In the present study, the reinstatement phenomenon was assessed in mice using a differential conditioned suppression paradigm. In a first phase, one conditioned stimulus (CS + ) was consistently paired with an unconditioned stimulus (US; footshock) while another CS (CS-) was not, resulting in selective suppression of previously trained instrumental behaviour during the CS + . After the extinction phase, half of the animals (reinstatement group) were presented with unsignalled USs, while the other half were not (control group). A differential return of conditioned responding was observed in the reinstatement group, but not in the control group. The implications of these findings for future conditioning research are discussed. PMID- 17853240 TI - Attention dependency in implicit learning of repeated search context. AB - How much attention is needed to produce implicit learning? Previous studies have found inconsistent results, with some implicit learning tasks requiring virtually no attention while others rely on attention. In this study we examine the degree of attentional dependency in implicit learning of repeated visual search context. Observers searched for a target among distractors that were either highly similar to the target or dissimilar to the target. We found that the size of contextual cueing was comparable from repetition of the two types of distractors, even though attention dwelled much longer on distractors highly similar to the target. We suggest that beyond a minimal amount, further increase in attentional dwell time does not contribute significantly to implicit learning of repeated search context. PMID- 17853241 TI - A little learning is a dangerous thing: an experimental demonstration of ignorance-driven inference. AB - Studies of ignorance-driven decision making have been employed to analyse when ignorance should prove advantageous on theoretical grounds or else they have been employed to examine whether human behaviour is consistent with an ignorance driven inference strategy (e.g., the recognition heuristic). In the current study we examine whether - under conditions where such inferences might be expected - the advantages that theoretical analyses predict are evident in human performance data. A single experiment shows that, when asked to make relative wealth judgements, participants reliably use recognition as a basis for their judgements. Their wealth judgements under these conditions are reliably more accurate when some of the target names are unknown than when participants recognize all of the names (a "less-is-more effect"). These results are consistent across a number of variations: the number of options given to participants and the nature of the wealth judgement. A basic model of recognition based inference predicts these effects. PMID- 17853242 TI - Dissimilarity is used as evidence of category membership in multidimensional perceptual categorization: a test of the similarity-dissimilarity generalized context model. AB - In exemplar models of categorization, the similarity between an exemplar and category members constitutes evidence that the exemplar belongs to the category. We test the possibility that the dissimilarity to members of competing categories also contributes to this evidence. Data were collected from two 2-dimensional perceptual categorization experiments, one with lines varying in orientation and length and the other with coloured patches varying in saturation and brightness. Model fits of the similarity-dissimilarity generalized context model were used to compare a model where only similarity was used with a model where both similarity and dissimilarity were used. For the majority of participants the similarity dissimilarity model provided both a significantly better fit and better generalization, suggesting that people do also use dissimilarity as evidence. PMID- 17853243 TI - Serial position functions for recognition of olfactory stimuli. AB - Two experiments examined item recognition memory for sequentially presented odours. Following a sequence of six odours participants were immediately presented with a series of two-alternative forced-choice (2AFC) test odours. The test pairs were presented in either the same order as learning or the reverse order of learning. Method of testing was either blocked (Experiment 1) or mixed (Experiment 2). Both experiments demonstrated extended recency, with an absence of primacy, for the reverse testing procedure. In contrast, the forward testing procedure revealed a null effect of serial position. The finding of extended recency is inconsistent with the single-item recency predicted by the two component duplex theory (Phillips & Christie, 1977). We offer an alternative account of the data in which recognition accuracy is better accommodated by the cumulative number of items presented between item learning and item test. PMID- 17853244 TI - Caffeine deprivation state modulates expression of acquired liking for caffeine paired flavours. AB - Previous studies found that caffeine consumers acquired a liking for the flavour of novel caffeinated drinks when these drinks were consumed repeatedly in a caffeine-deprived, but not nondeprived, state. Expression of this acquired liking appeared acutely sensitive to current caffeine deprivation state, but the use of between-subjects designs confounded interpretation of those studies. The present study evaluated these findings further using a within-subject design, with one flavour paired with caffeine (CS + ) and the second with the absence of caffeine (CS-). During four CS + and four CS- training days, 32 moderate caffeine consumers alternatively consumed a novel flavoured drink a CS + paired with caffeine and a CS- flavour paired with placebo. Participants evaluated both drinks before and after training in two motivational states: caffeine deprived and nondeprived. As predicted, pleasantness ratings for the caffeine-paired flavour increased overall. However, this acquired liking was only significant when tested in a caffeine-deprived state. These data are consistent with a conditioned-flavour preference model and imply that expression of acquired liking for a novel caffeinated flavour depends on the need for the effects of caffeine at the time when the drink is evaluated. PMID- 17853245 TI - Distractor repetitions retrieve previous responses to targets. AB - Response retrieval theories assume that stimuli and responses become integrated into "event files" (Hommel, 1998) in memory so that a second encounter with a specific stimulus automatically retrieves the response that was previously associated with this stimulus. In this article, we tested a specific prediction of a recent variant of stimulus retrieval theories as introduced by Rothermund, Wentura, and De Houwer (2005): In selection tasks where target stimuli are accompanied by distractors, responses to target stimuli are automatically bound to distractor stimuli as well; repeating the distractor should retrieve the response to the target that formerly accompanied the distractor. In three experiments we confirmed this prediction: Distractor repetition facilitated responding in the probe in the case of response repetition whereas repeating the distractor delayed responding in the case of response change. PMID- 17853246 TI - The effects of cognitive demand upon relationships between working memory and cognitive skills. AB - The present study explored the effects of cognitive demand upon relationships between working memory and cognitive skills. Both children and adults were tested on a measure of short-term memory and three measures of counting span, which varied in cognitive demand. When statistically controlling for short-term memory and the speed of counting operations, the more demanding the counting-span task, the closer its relationship with cognitive skills. The results are discussed in terms of practical and theoretical implications for working memory research. PMID- 17853247 TI - Positive and negative generation effects in source monitoring. AB - Research is mixed as to whether self-generation improves memory for the source of information. We propose the hypothesis that positive generation effects (better source memory for self-generated information) occur in reality-monitoring paradigms, while negative generation effects (better source memory for externally presented information) tend to occur in external source-monitoring paradigms. This hypothesis was tested in an experiment in which participants read or generated words, followed by a memory test for the source of each word (read or generated) and the word's colour. Meiser and Broder's (2002) multinomial model for crossed source dimensions was used to analyse the data, showing that source memory for generation (reality monitoring) was superior for the generated words, while source memory for word colour (external source monitoring) was superior for the read words. The model also revealed the influence of strong response biases in the data, demonstrating the usefulness of formal modelling when examining generation effects in source monitoring. PMID- 17853248 TI - Colours sometimes count: awareness and bidirectionality in grapheme-colour synaesthesia. AB - Three experiments were conducted with 10 grapheme-colour synaesthetes and 10 matched controls to investigate (a) whether awareness of the inducer grapheme is necessary for synaesthetic colour induction and (b) whether grapheme-colour synaesthesia may be bidirectional in the sense that not only do graphemes induce colours, but that colours influence the processing of graphemes. Using attentional blink and Stroop paradigms with digit targets, we found that some synaesthetes did report "seeing" synaesthetic colours even when they were not able to report the inducing digit. Moreover, congruency effects (effects of matching the colour of digit presentation with the synaesthetic colour associated with that digit) suggested that grapheme-colour synaesthesia can be bidirectional, at least for some synaesthetes. PMID- 17853250 TI - Hearing facial identities. AB - While audiovisual integration is well known in speech perception, faces and speech are also informative with respect to speaker recognition. To date, audiovisual integration in the recognition of familiar people has never been demonstrated. Here we show systematic benefits and costs for the recognition of familiar voices when these are combined with time-synchronized articulating faces, of corresponding or noncorresponding speaker identity, respectively. While these effects were strong for familiar voices, they were smaller or nonsignificant for unfamiliar voices, suggesting that the effects depend on the previous creation of a multimodal representation of a person's identity. Moreover, the effects were reduced or eliminated when voices were combined with the same faces presented as static pictures, demonstrating that the effects do not simply reflect the use of facial identity as a "cue" for voice recognition. This is the first direct evidence for audiovisual integration in person recognition. PMID- 17853249 TI - Focus identification during sentence comprehension: evidence from eye movements. AB - Three eye movement experiments investigated focus identification during sentence comprehension. Participants read dative or double-object sentences (i.e., either the direct or indirect object occurred first), and a replacive continuation supplied a contrast that was congruous with either the direct or the indirect object. Experiments 1 and 2 manipulated focus by locating only adjacent to either the direct or indirect object of dative (Experiment 1) or double-object (Experiment 2) sentences. Reading-time effects indicated that the surface position of the focus particle influenced processing. In addition, Experiment 1 reading times were longer when the replacive was incongruous with the constituent that only adjoined, and particle position modulated a similar effect in Experiment 2. Experiment 3 showed that this effect was absent when only was omitted. We conclude that the surface position of a focus particle modulates focus identification during on-line sentence comprehension. PMID- 17853251 TI - Risperidone monotherapy in manic inpatients: an open label, multicentre trial. AB - OBJECTIVE: The efficacy of risperidone in acute mania has been established in several controlled clinical studies. However, this may not necessarily resemble the clinical effectiveness of this treatment, as patient populations in controlled studies are considered as being not representative. This study examined risperidone monotherapy in a sample of severe manic patients in admission ward settings. METHODS: Open label monotherapy with risperidone was examined for 3 weeks in 30 inpatients. Subjects were evaluated with structured clinical rating scales: Young Mania Rating Scale (YMRS), Clinical Global Impression, bipolar version (CGI-BP), and the Extrapyramidal Symptom Rating Scale (ESRS). In addition, the amount of concomitant use of benzodiazepines was documented. Data were analysed using a last observation carried forward method on all subjects given medication at baseline. RESULTS: Significant improvement from baseline to exit was observed both for the YMRS and CGI-BP. Responder analysis revealed that two-thirds of the patients showed a reduction of 50% in the YMRS score, and 69% of the patients were rated as very much improved or much improved on the CGI-BP mania scale at study exit. Only three patients dropped out due to adverse events, in one case due to extrapyramidal symptoms. CONCLUSIONS: The efficacy of risperidone in the acute treatment of mania as observed in controlled studies could be replicated in this open monotherapy study in a severely manic inpatient population. Considering the mean maximal dosage of 5.5+/-0.9 mg risperidone, the tolerability and safety profile appeared satisfactory. PMID- 17853252 TI - Deficit of pericapillary oligodendrocytes in the prefrontal cortex in schizophrenia. AB - OBJECTIVE: Our previous studies have shown a significant decrease of numerical density of oligodendrocytes in the prefrontal cortex in postmortem schizophrenic brains. Deficit of oligodendrocytes was associated with loss of oligodendroglial satellites of pyramidal neurons. In this study we tested the hypothesis that there might be a deficit and loss of pericapillary oligodendrocytes in the prefrontal cortex in schizophrenia. METHOD: Autopsy samples from the prefrontal cortex (BA 10) were obtained from 12 normal controls and 12 chronic schizophrenic cases. Capillaries and oligodendrocytes were viewed in paraffin sections stained with a Luxol-fast blue and cresyl violet. Electron microscopy was applied to study the ultrastructure of oligodendrocytes. For morphometric analysis, an average of 100 rectilinear capillary segments from layer V was sampled for each individual. The number of oligodendrocytes visible along rectilinear segments was expressed as the number of oligodendrocytes per 0.01 mm of capillary length. RESULTS: Subjects with schizophrenia had a significantly lower (-23%; P < 0.005) number of pericapillary oligodendrocytes compared to controls. Prominent ultrastructural dystrophic and degenerative alterations of pericapillary oligodendrocytes have been revealed in schizophrenic brains. CONCLUSION: The present study provides evidence that there is a prominent reduction, damage and loss of pericapillary oligodendrocytes in the prefrontal cortex in schizophrenia. These changes may contribute to the pathophysiological basis for altered blood brain barrier and lowered metabolic rates in subjects with schizophrenia. PMID- 17853253 TI - Adverse drug events and medication errors in psychiatry: methodological issues regarding identification and classification. AB - Abstract Adverse drug events and medication errors have received extensive study recently in a variety of clinical populations, though compared to many other areas relatively little work has focused on this area in psychiatry, especially with respect to the contribution of error to harm. The goal of this paper is to discuss methodological issues around measurement of medication safety in psychiatric patients. Against the background of a systems approach, a modern perspective of error management is discussed, and a multidimensional procedure for detection and classification of incidents related to the medication process is presented. This method has proven successful in non-psychiatric settings yielding the current best estimate of error rates and providing insight into the underlying causes. While this general approach can be adapted to the psychiatric setting, a number of issues make measurement especially challenging in psychiatry. These include the fluctuating course of psychiatric disorders, reduced patient adherence to the medication process, adverse effects which are often similar to symptoms of the underlying disorder, the frequent use of wide dose intervals depending on the clinical situation, and the presence of many drug drug interactions. Data collected by means of the presented approach provide a basis for the development of effective strategies to reduce the risk of medication errors and thus improve patient safety in psychiatric care. PMID- 17853254 TI - Association study of paroxetine therapeutic response with SERT gene polymorphisms in patients with major depressive disorder. AB - We investigated the relationships between LS promoter (SERTPR) and ls intron2 (SERTin2) genetic variants of serotonin transporter (SERT) polymorphisms with treatment response in 130 patients with major depressive disorder (MDD) treated with paroxetine (20 mg/day) for 6 weeks. To assess and evaluate therapeutic response to paroxetine all patients were rated weekly using the HAMD-17 scale. Responders were defined as those subjects with a decrease in HAMD scale by > or = 50% at week 6 of treatment. Comparison of genotypes and alleles frequency of the SERTPR between responders and nonresponders revealed significant differences among genotypes and overrepresentation of the S allele in the group of non responders (P = 0.0004). SERTin2-ss genotype bearing subjects showed better treatment response compared to ls and ll genotype from the fourth week of treatment (P = 0.035). Statistical differences were also found in distributions of the estimated haplotypes between responders and non-responders, while subsequent analysis revealed overrepresentation of S/l haplotype (P = 0.006) in the group of non-responders. SERTPR and SERTin2 were found to be in linkage disequilibrium in studied population. These findings identify genetic factors associated with paroxetine treatment response in MDD patients. PMID- 17853255 TI - Blood pressure is associated with cognitive impairment in young hypertensives. AB - AIMS: The present study was conducted to assess the effects of duration of hypertension, systolic hypertension, diastolic hypertension, drug compliance and class-of-drug on cognitive functions. METHODS AND RESULTS: A cohort of young hypertensive subjects was recruited after obtaining informed consent. Subjects with confounding factors, e.g., substance use, neurological disorders, endocrinopathies, inflammatory conditions, psychiatric illnesses, etc., were excluded. Their average systolic and diastolic blood pressure since onset of illness and prescribed drugs were noted from the records. Compliance was assessed with the help of information from subjects as well as the close relatives. MMSE and a battery of neuropsychological tests (Digit Span Test, Trail Making Test Form B, Stroop Test, Visuospatial Working Memory Matrix and Word Fluency Test) was applied to all the participants. Multivariate regression analysis was used for the assessment of associations and one-way ANOVA was performed to assess differences in the mean. Analysis showed that mean age of study subject was 52 years and average duration of hypertension was 9 years. Fourteen percent subjects had obvious cognitive impairment as suggested by MMSE score less than 23. However, when cut-off score was lowered to 20, only 6% subjects fell into this category. Diastolic blood pressure had significant negative association with all of the cognitive measures except Trail Making Test, which was, on the contrary, significantly and negatively associated with systolic blood pressure. Duration of hypertension did not influence cognitive performance in this study. Effect of drug compliance was somewhat variable, but in general good compliance was associated with better cognitive performance. Beta-Blocker therapy hampered cognitive performance, whereas the best performance, especially on tests of semantic memory and pre-frontal functions was seen in subjects taking calcium channel blockers. CONCLUSIONS: Diastolic hypertension was associated with significant impairment of cognitive functions in younger subjects. On the other hand good compliance and calcium channel blockers had protective effect on hypertension induced cognitive impairment, especially on the prefrontal functions. PMID- 17853256 TI - The Wisconsin Card Sorting Test and the N-back test in mild cognitive impairment and elderly depression. AB - The aim of this study was to assess cognitive functions in 30 non-depressed patients with mild cognitive impairment (MCI), compared with 30 age-, gender- and education-matched patients with acute depressive episode, and with 30 healthy subjects. Neuropsychological assessment included the Mini Mental State Examination (MMSE), memory tests as well as the Wisconsin Card Sorting Test (WCST) and the N-back test. Patients with MCI obtained significantly worse results on all domains of the WCST and the N-back test compared to both depressed and healthy subjects. Depressed patients showed significantly worse performance than controls on most scores. In the MCI group, no association with MMSE was found with any of WCST domains, or with reaction time in the N-back test. Three tests, WCST-P, N-back %CORR and WCST 1st CAT obtained highest ranks (>90) as predictors for differentiating between groups. The results suggest a usefulness of employing WCST and N-back tests for a neuropsychological evaluation of patients with MCI. PMID- 17853257 TI - Combined use of ECT with aripiprazole. AB - This case report is on the combined use of electroconvulsive treatment (ECT) with a partial dopamine agonist, aripiprazole, in the treatment of a 30-year-old man with chronic and refractory paranoid schizophrenia. The patient had been under high doses of typical and atypical antipsychotics with a lack of control of the symptoms, characterized by agitation, suspiciousness, and obsessive fears. ECT therapy was started while receiving antipsychotic treatment and aripiprazole was added to the pharmacological treatment after six sessions of ECT. The convulsive threshold and the seizure duration did not significantly change after the treatment with aripiprazole was initiated. There was a clinical improvement after the combined treatment with ECT and aripiprazole and the combination was well tolerated. PMID- 17853258 TI - The changes of AgNOR parameters of anterior cingulate pyramidal neurons are region-specific in suicidal and non-suicidal depressive patients. AB - The anterior cingulate cortex (AC) is consistently implicated in the pathophysiology of depression. While suicide has been shown in previous reports to be closely related to depression, it is still a distinct phenomenon. The aim to differentiate between depression and suicide was approached by the karyometric analysis of AC pyramidal neurons. The study was performed on paraffin-embedded brains from 20 depressive patients (10 of whom had committed suicide) and 24 matched controls. The karyometric parameters of the layer III and V pyramidal neurons of the dorsal and ventral AC were evaluated bilaterally by Argyrophilic Nucleolar Organiser (AgNOR) silver staining method. Control-specific was the increased nuclear area in ontogenetically younger pyramidal neurons layer III in the left dorsal compared with ventral AC (Wilcoxon test, P<0.01). The decreased AgNOR number per nucleus in these cells in the right ventral AC was depression specific compared with controls (t-test, P=0.047). On the other hand, the diffuse decrease in AgNOR ratio throughout pyramidal neurons on the left side was specific for suicidal depressive patients compared with non-suicidal patients and controls (ANOVA, P=0.028). The results suggest that regionally differentiated depression- and suicide-specific disturbed function of the most important AC output cells exists in depressive patients. PMID- 17853259 TI - Bispectral index monitoring during dissociative pseudo-seizure. AB - Severe forms of dissociation or conversion can lead to events clinically often described as pseudo-seizures. Borderline personality disorder is a clinical condition which is often accompanied by a high susceptibility for dissociation and dissociative states are characterized by memory disturbance and perceptual alterations. We report a case of a patient with a complete anaesthesia, paralysis and amnesia for about 1 h. Within this time period we measured a bispectrum EEG index called BIS. Deepest recorded BIS value was 47. The described pattern of short but deep BIS reductions is completely discongruent to the findings during physiological sleep, during general anaesthesia, but very similar (and even more pronounced) to those during self-hypnosis. This makes former assumptions plausible that hypnosis and severe forms of dissociation (or conversion) may share common aetiologies. PMID- 17853260 TI - Prediction of symptom remission in schizophrenia during inpatient treatment. AB - OBJECTIVE: Standardized consensus criteria for remission in schizophrenia were recently proposed. The present study applied the symptom-severity component of these criteria to a sample of inpatients in order to determine the rates of remission during inpatient treatment and to explore predictors of remission. METHOD: A total of 288 inpatients from a multi-centre follow-up programme who fulfilled ICD-10 criteria for schizophrenia were included in the present analyses. PANSS ratings at admission and at discharge from hospitalization were used to examine remission status. Clinical and sociodemographic variables at admission were tested for their ability to predict remission at discharge. RESULTS: In total, 55% of the sample achieved symptom remission during inpatient treatment; 84% percent showed remission with respect to 'reality distortion', 85% with respect to 'disorganization' and only 65% with respect to 'negative symptoms'. Logistic regression analysis revealed that the global functioning (GAF) in the year before admission, the total score of the Strauss-Carpenter Prognostic Scale and the PANSS negative subscore at admission were predictive for symptom remission. The regression model showed a predictive value of about 70% and explained 36% of the observed variance. CONCLUSION: The results highlight the impact of negative symptoms for the course and treatment response of schizophrenic illness. PMID- 17853263 TI - Turning order into chaos through repetition and addition of elementary acts in obsessive-compulsive disorder (OCD). AB - A concept and methodology derived from an animal model provided the framework for a study of rituals in obsessive compulsive disorder (OCD) patients and yielded objective and observable criteria applicable for compulsive rituals across patients. The employed ethological approach should be able to reveal and identify a common structure underlying OCD rituals, pointing to shared psychopathology. Eleven OCD rituals performed by patients in their own home were videotaped and compared with the behaviour of healthy individuals instructed to perform the same rituals. The videotaped rituals were deconstructed into visits to specific locations or objects (ritual space), and to the acts performed at each location/object (ritual basic components). Quantitative analyses revealed that compulsiveness emanates from the expansion of repeats for some acts and visits, and from the addition of superfluous act types. Best discrimination between OCD and control rituals (90.9% success) was provided by the parameter "maximum of act repeats in a ritual" (R(2)=0.77). It is suggested that the identified properties of compulsive behaviour are consistent with a recent hypothesis that ritualized behaviour shifts the individual's attention from a normal focus on structured actions to a pathological attraction onto the processing of basic acts, a shift that invariably overtaxes memory. Characteristics and mechanisms of compulsive rituals may prove useful in objective assessment of psychiatric disorders, behavioural therapy, and OCD nosology. PMID- 17853265 TI - Brugada syndrome as a potential cardiac risk factor during electroconvulsive therapy (ECT). AB - A case of asystole (> 5 s) during electroconvulsive therapy (ECT) is reported in a patient who was subsequently diagnosed to have Brugada syndrome (BS). This hereditary sodium-channelopathy is characterized by typical, though intermittent, ECG abnormalities and carries a high risk of ventricular arrythmia and sudden cardiac death. The general occurence of BS is rare; however, it is more prevalent in men and in southeast Asian populations. As in the reported case, BS carriers may lack a telltale medical history and can present with normal ECG recordings. In these cases, BS can only be unmasked by repeated ECG recordings over time or by specialist cardiological examinations. To our knowledge, BS, which was first characterized in 1992, has not yet been in the focus of cardiac complications during ECT. However, as the presented case illustrates, this syndrome should be considered as a rare but potentially severe cardiac risk factor in the context of ECT. PMID- 17853266 TI - Therapeutic strategies for catatonia in paraneoplastic encephalitis. AB - This report is about a 40-year-old man suffering from fluctuating catatonia as main symptom of long-lasting paraneoplastic encephalitis caused by a testicular neoplasm. With recurrence of a neoplasm initially diagnosed as seminoma after a 7 year symptom-free interval the patient suddenly developed various neurological and psychopathological symptoms including seizures, autonomic dysregulation, continuous anterograde short-term amnesia and predominantly a long-lasting complex catatonic syndrome with on-off phenomena. Repeated MRI scans of the brain showed no pathology; brain FDG-PET scans indicated a hypometabolism of the frontal cortex and the left temporal lobe. Eventually a paraneoplastic encephalitis was diagnosed. Repeated resections of tumour recurrences and plasmapheresis moderately alleviated catatonic symptoms. Haloperidol and lorazepam effectively relieved catatonic symptoms in contrast to various atypical antipsychotic drugs and diazepam. A series of 12 electroconvulsive treatments (ECT) temporarily improved residual catatonic symptoms such as catalepsy, stupor and mutism. Further neoplasm recurrences, however, reinforced catatonia until the tumour was successfully treated and the patient fully recovered. This case report illustrates the potential but also the limitations of various therapeutic approaches in organic catatonia due to paraneoplastic encephalitis. PMID- 17853268 TI - Bilateral ankle oedema in a patient taking escitalopram. AB - Escitalopram (ESC) is the S-isomer of the racemic compound citalopram, and has been shown to be an efficacious treatment for major depressive disorder. Several studies or case reports are available describing its side effects, none of which however refer to its potential to induce ankle oedema. We report the case of a 69 year-old female depressed patient who, after approximately 1 month of therapy with ESC, progressively titrated up to 30 mg/day, developed a bilateral ankle oedema, which resolved completely within the first week following its discontinuation. PMID- 17853269 TI - Obsessive-compulsive disorder followed by psychotic episode in long-term ecstasy misuse. AB - AIM: We report the case of two young subjects who developed an obsessive compulsive disorder (OCD) during a heavy use of ecstasy. After several months of discontinuation of the drug, major depression with psychotic features developed in one subject and a psychotic disorder in the other individual. No mental disorder preceded the use of ecstasy in any subject. FINDINGS: A familial and personality vulnerability for mental disorder was revealed in one subject, but not in the other, and all physical, laboratory and cerebral NMR evaluations showed normal results in both patients. Remission of OCD and depressive episode or psychotic disorder was achieved after treatment with a serotoninergic medication associated with an antipsychotic. CONCLUSIONS: The heavy long-term use of ecstasy may induce an alteration in the brain balance between serotonin and dopamine, which might constitute a pathophysiological mechanism underlying the onset of obsessive-compulsive, depressive and psychotic symptoms. The heavy use of ecstasy probably interacted with a vulnerability to psychiatric disorder in one subject, whereas we cannot exclude that an "ecstasy disorder" ex novo affected the other individual. PMID- 17853270 TI - The glucocorticoid receptor gene exon 1-F promoter is not methylated at the NGFI A binding site in human hippocampus. AB - Recent research has demonstrated that early life experience, such as variation in maternal care, can have a profound impact on the physiological and endocrine stress response of Rattus norvegicus. Low maternal care resulted in increased methylation of the nerve growth factor-inducible protein A (NGFI-A, EGR1) binding site located in the hippocampal glucocorticoid receptor gene (Nr3c1) exon 1(7) promoter, leading to decreased Nr3c1 expression, which results in a reduced efficiency of glucocorticoid-mediated negative feedback on hypothalamus-pituitary adrenal axis activity. The human glucocorticoid receptor gene (NR3C1) has a highly similar 5' structure compared to the rat, and the human alternative exon 1 F is the orthologue to the rat exon 1(7). Based upon the evidence from rats, and the high sequence identity of the regulatory sequences, we examined the methylation pattern of the corresponding NGFI-A binding site in the human glucocorticoid receptor exon 1-F specific promoter in post mortem hippocampal tissue. In contrast to the findings in rats, neither of the two CpG motifs within the NGFI-A binding site was methylated in the 32 subjects investigated. These observations might reflect different promoter methylation patterns in humans and rats. PMID- 17853271 TI - Risperidone versus haloperidol for facial affect recognition in schizophrenia: findings from a randomised study. AB - Patients with schizophrenia consistently fail to perform facial affect recognition tasks as accurately as healthy controls. So far, the effects of different antipsychotic drugs on this deficit, as well as the mechanisms through which these drugs may exert their influence on face processing models, remain poorly understood. Twenty-five hospitalised acute schizophrenic patients were randomised to either haloperidol or risperidone following their admission. Patients performed a facial affect discrimination task. In order to differentiate drug effects on perceptive versus semantic processing of faces, the evaluation also included two facial identity discrimination tasks (inverted and upright faces). All evaluations were performed before treatment initiation, after 2 weeks and after 4 weeks of treatment. Compared with patients receiving haloperidol, patients receiving risperidone showed better discrimination of facial affect and inverted faces, but not of upright faces. Differential drug effects were most prominent 2 weeks after treatment initiation. Performance on inverted faces accounted for only 1% of the variance in affect discrimination. Additionally, there was an inverse relationship between negative symptoms and performance on upright-face identification and affect discrimination, with the strongest and most significant correlation being for affect discrimination. Our findings suggest that the preferential effect of risperidone on affect discrimination is unlikely to be due to global effects on general face processing. Moreover, although risperidone appears to enhance the processing of individual salient facial features, this effect cannot explain the improvement in affect recognition. We conclude that risperidone may specifically act on the processing of emotion-laden information. PMID- 17853273 TI - Differential diagnosis of coagulation abnormalities in borderline personality disorder. AB - We report the case of a 26-year-old woman suffering from borderline personality disorder (BPD), major depression and bulimia nervosa according to DSM-IV who showed unexplained impairment of the vitamin K-dependent coagulation pathway. Subsequently we discuss different manifestations of self damaging behaviour and comorbidities, as well as psychosocial issues potentially leading to coagulation abnormalities or complications in patients with BPD. PMID- 17853274 TI - Repeated intravenous ketamine therapy in a patient with treatment-resistant major depression. AB - BACKGROUND: The intravenous administration of ketamine, an N-methyl-D-aspartate receptor antagonist, results in a great improvement of depression symptoms, but it is not clear for how long. This single-case trial was conducted to explore the duration of improvement and the effects of a second administration on the clinical outcome. METHODS: In an open label trial, a 55-year-old male patient with treatment-resistant major depression and a co-occurring alcohol and benzodiazepine dependence received two intravenous infusions of 0.5 mg/kg ketamine over the course of 6 weeks. Depression severity was assessed by means of a weekly clinical interview, the 21-item Hamilton Depression Rating Scale (HDRS), and the 21-item Beck Depression Inventory (BDI). RESULTS: The first ketamine infusion lead to a pronounced improvement of symptoms, peaking on the second day post infusion (HDRS -56.6%, BDI -65.4%). Positive effects started fading by day 7, reaching baseline by day 35. The second infusion was less efficacious: HDRS and BDI were reduced by 43 and 35%, respectively, and returned to baseline by day 7. CONCLUSION: In this patient with a co-occurring substance use disorder, repeated administrations of ketamine produced positive results. Since the second application has been less efficacious, doses and schedule of administrations need to be further investigated. PMID- 17853277 TI - Quetiapine for the treatment of bipolar II depression: analysis of data from two randomized, double-blind, placebo-controlled studies. AB - OBJECTIVE: To investigate the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar II disorder. METHODS: A post-hoc evaluation was conducted in 351 patients with bipolar II depression combined from two similarly designed double-blind, randomized, placebo-controlled, 8-week studies of quetiapine (300 or 600 mg/day) that included patients with bipolar I or II disorder (DSM-IV) exhibiting moderate to severe depression. The primary endpoint was change from baseline to week 8 in MADRS total score. Secondary endpoints included HAM-D, HAM-A, and CGI. RESULTS: In patients with bipolar II disorder, improvement in mean MADRS total score from baseline was significantly greater with quetiapine 300 (n = 107) and 600 mg/day (n = 106) from the first assessment (week 1) through week 8 compared with placebo (n = 108). The mean change from baseline at week 8 for quetiapine 300 and 600 mg/day versus placebo was -17.1 and -17.9 versus -13.3 (P = 0.005 and P = 0.001 versus placebo), respectively. Change in HAM-D, HAM-A, and CGI were also significantly greater for quetiapine groups versus placebo. Common adverse events in the quetiapine groups included dry mouth, sedation, and somnolence. CONCLUSION: Quetiapine demonstrated significant efficacy as monotherapy, compared with placebo, for the treatment of acute depressive episodes in bipolar II disorder. PMID- 17853278 TI - Nonlinear analysis of heart rate variability in patients with eating disorders. AB - Patients with anorexia nervosa or bulimia nervosa often have signs of autonomic dysfunction potentially deleterious to the heart. The aim of this study was to ascertain the nonlinear properties of heart rate variability in patients with eating disorders. A group of 33 women with eating disorders (14 anorexia, 19 bulimia) and 19 healthy controls were included in the study. Conventional time- and frequency-domain heart rate variability measurements, along with nonlinear heart rate variability measurements including the short-term fractal scaling exponent alpha and approximate entropy (ApEn) were calculated. Anorexia nervosa patients exhibited decreased values of alpha, while bulimia nervosa patients had decreased values of ApEn. Low-frequency heart rate variability was decreased in patients with anorexia. In conclusion, these results are compatible with the view that a more severe alteration of cardiac autonomic function is present in anorexia than in bulimia. PMID- 17853279 TI - Pica responding to SSRI: an OCD spectrum disorder? AB - Pica is a common disorder in childhood, however, in adults it is associated with mental retardation, psychosis and pregnancy. A few case reports have described it being associated with obsessive compulsive disorder in adults. We describe the case of an adult female patient who developed an impulse to ingest chalk only in stressful situations. These thoughts were ego-dystonic and kept on hammering her mind until she ate it. She was diagnosed as having Major Depressive Disorder with relational problems and pica. We prescribed her escitalopram with clonazepam and asked her to ventilate her feelings during stressful situations. Her depression improved within three weeks, with remarkable improvement in pica symptoms. We concluded that stress may induce the pica in some adults and that such feelings have impulsive/compulsive characters. In addition, appropriate management of stress may help to alleviate the symptoms of pica. PMID- 17853280 TI - Serum levels of aripiprazole and dehydroaripiprazole, clinical response and side effects. AB - Aripiprazole, a novel antipsychotic drug, is metabolized by CYP3A4 and CYP2D6 forming mainly its active metabolite dehydroaripiprazole. In this study, aripiprazole and dehydroaripiprazole serum levels of psychiatric patients were measured and related to dose, comedication, and clinical effects including therapeutic and side effects. Patients were treated with mean doses of 20 +/- 8 mg/day of aripiprazole (median 15 mg, range 7.5-60 mg). Serum levels correlated significantly with the dose (r = 0.419; P < 0.01), with a mean value of aripiprazole of 214 +/- 140 ng/ml. Mean concentrations of the active metabolite dehydroaripiprazole amounted to 40% of the parent compound. Comedication with CYP3A4 and CYP2D6 inducers or inhibitors changed serum levels up to 51%. Improvement was best in patients with a serum level between 150 and 300 ng/ml. No or only mild side effects were detected in patients, with aripiprazole plasma concentrations between 110 and 249 ng/ml. A total of 32% of the patients who received no other antipsychotic drug besides aripiprazole reported side effects; tension being the most frequent one. Since serum levels of aripiprazole and dehydroaripiprazole were highly variable between individuals, and distinct ranges were associated with good therapeutic response and minimal side effects, it seems likely that therapeutic drug monitoring can be helpful to improve the antipsychotic drug therapy. PMID- 17853281 TI - Women with coronary artery disease and depression: a neglected risk group. AB - Coronary artery disease (CAD) has been held to be a "male" disease due to men's higher absolute risk compared to women, but the relative risk of women for CAD morbidity and mortality is actually higher. The purpose of this article is to review research evidence for gender differences in CAD and depression with special emphasis on women. Current knowledge points to important gender differences in age of onset, symptom presentation, management, outcome as well as traditional and psychosocial risk factors. Compared to men, CAD risk in women is more strongly increased by some traditional factors (diabetes, hypertension, hypercholesterolemia, obesity), and socioeconomic and psychosocial factors seem to have a higher impact on CAD in women as well. With respect to differences in CAD management, a gender-bias in favour of men has to be taken into account in spite of older age and higher comorbidity in women, possibly contributing to a poorer outcome. Depression was shown to be an independent risk factor and consequence of CAD; however, concerning gender differences, the results have been inconsistent. Current evidence suggests that depression causes a greater increase in CAD incidence in women, and that female CAD patients experience higher levels of depression than men. Gender aspects should be more intensively considered both in further research on gender differences in comorbid depression and in cardiac treatment and rehabilitation with the goal of making secondary prevention for women more effective. PMID- 17853283 TI - Parental psychiatric hospitalisation and offspring schizophrenia. AB - The risk of schizophrenia has been linked with a family history of schizophrenia and less strongly with other psychiatric disorders in family members. Using data from the Copenhagen Perinatal Cohort and from the Danish Psychiatric Case Register, we studied the relationship between offspring risk of schizophrenia and a range of psychotic and non-psychotic psychiatric diagnoses in parents. Psychiatric admission data after 1969 were available for 7047 cohort members born between 1959 and 1961, and for 7006 mothers and 6993 fathers. Univariate analysis showed that neurosis, alcohol and substance dependence in both parents were associated with elevated risk of offspring schizophrenia; in addition, maternal schizophrenia, affective disorder and personality disorder were associated with elevated risk. Controlling for parental age, parental social status, and parental psychiatric co-diagnosis, offspring risk of schizophrenia was associated with maternal schizophrenia (OR = 15.41 with 95% CI 5.96-39.81) and, independently, with paternal hospitalisation with neurosis (OR = 5.90 with 95% CI 2.23-15.62). The risk of schizophrenia associated with paternal neurosis remained significant after excluding offspring of parents with non-affective psychosis from the sample. These findings suggest that genetic and family studies should not only focus on parental history of schizophrenia since the simple distinction between positive and negative family history could not accurately describe offspring risk in this sample. PMID- 17853284 TI - Perfectionism and sleep disturbance. AB - The main purpose of the present research was to explore gender-related associations between sleep disturbance and perfectionism dimensions in a large sample of undergraduate students. Perfectionism dimensions have been assessed using the Portuguese version of the Multidimensional Perfectionism Scale (Hewitt and Flett, 1991 , J Pers Soc Psychol 60:456; Soares et al., 2003 , Rev Port Psicossom 5:46) and sleep disturbance with two items concerning difficulties initiating sleep and difficulties maintaining sleep. A total of 1163 undergraduate students of both genders between 17 and 25 years of age completed the scale. Results from correlational and categorial analyses indicated that socially prescribed perfectionism was the only dimension associated with sleep disturbance in undergraduate students of both genders. Males with the highest levels of socially prescribed perfectionism were approximately twice more likely to report sleep disturbances than those with less socially prescribed perfectionism. Similar results were found within the female sample. Implications for future research and clinical practice are discussed. PMID- 17853285 TI - Serum markers of brain-cell damage and C-reactive protein are unaffected by electroconvulsive therapy. AB - The effects of electroconvulsive therapy (ECT) on serum levels of the acute-phase reactant C-reactive protein (CRP) and intracellular enzymes such as alkaline phosphatase (ALP), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK), have received little attention. If brain cells are damaged, CK-BB, LDH and AST levels are expected to show (minor) elevations. We measured serum levels of prolactin, AST, ALT, LDH, ALP, CK and CRP before and 5 min, 30 min, 4 h, 1 day, 2 days, and 3 days after ECT in 15 consecutive patients (eight women and seven men; mean 53.9 years old, range 3082) who did not receive ECT in the preceding 2 weeks. Prolactin levels increased (P = 0.001), but none of the other mean concentrations significantly increased over time. All concentrations remained within the normal range in every patient, except for five samples with elevated CK levels (range 333-675 IU/l). CK MB and CK-BB fractions, however, remained low, indicating that skeletal muscle was the source of the CK elevation. Serum levels of markers of brain cell leakage and inflammation remained low following one ECT session, suggesting that ECT does not cause direct brain cell leakage, nor an inflammatory response. PMID- 17853290 TI - Neuroaetiology of chronic fatigue syndrome: an overview. AB - Chronic fatigue syndrome (CFS) is now recognized as a medial disorder. In contrast to recent related reports, the present review focuses primarily on aetiological aspects of CFS. Four major hypotheses are reviewed. (1) Although CFS is often associated with viral infection, the presence of viruses has as yet not consistently been detected. (2) It is not clear whether anomalies of the HPA axis often observed in CFS, are cause or the consequences of the disorder. (3) Immune dysfunction as the cause of CFS is thus far the weakest hypothesis. (4) The psychiatric and psychosocial hypothesis denies the existence of CFS as a disease entity. Accordingly, the fatigue symptoms are assumed to be the consequence of other (somatic) diseases. Other possible causes of CFS are oxidative stress and genetic predisposition. In CFS cognitive behavioural therapy is most commonly used. This therapy, however, appears to be ineffective in many patients. The suggested causes of CFS and the divergent reactions to therapy may be explained by the lack of recognition of subgroups. Identification of subtypes may lead to more effective therapeutic interventions. PMID- 17853291 TI - Vision in depressive disorder. AB - BACKGROUND: Reduced dopaminergic transmission has been implicated in the pathophysiology of major depression. Furthermore, dopaminergic neurotransmission plays an important role in the physiology of visual contrast sensitivity (CS). To test the hypothesis that altered dopaminergic neurotransmission plays a role in major depression we measured contrast sensitivity in patients with major depression and in healthy control subjects. METHODS: Twenty-eight patients diagnosed with major depressive disorder were compared to 21 age-matched control subjects on their ability to detect a Gabor target with slightly elevated luminance contrast embedded in seven equi-contrast distracters. RESULTS: Contrast discrimination thresholds were significantly elevated in unmedicated and medicated patients with major depression compared to control subjects, at all pedestal contrast levels tested. CONCLUSIONS: Contrast discrimination performance is reduced in depressive patients and might reflect a state of altered dopaminergic neurotransmission. PMID- 17853292 TI - Sleep-EEG patterns of school children suffering from symptoms of depression compared to healthy controls. AB - Depression in children is often an elusive disorder and its diagnostic tools are a matter of controversy. Several scales have been developed in an attempt to specifically detect some of the major aspects of depression, i.e. anhedonia, sadness, hopelessness. On the other hand, in adults depression frequently induces changes in sleep patterns, particularly a shortening in REM sleep latency. The alteration of sleep patterns in depressed children has been a matter of controversy. It is possible that a diagnostic deficiency might be the source of the contradictory reports. In the present study, The Child Depression Inventory, a rating scale specifically developed for child depression was applied to 396 school children (8-12 years of age). Nearly 15% of the children (N = 45) obtained scores higher than the established limit in this test for normal healthy subjects. A sample of children found within the highest (N = 25) and within the lowest (N = 25) scores in the scale were selected. After a clinical evaluation, only those who meet the inclusion criteria (N = 21 for depressed and N = 7 for healthy controls) were electroencephalographically recorded. Children with depressive symptoms showed a significant shortening in REM sleep latency (mean = 108 min) when compared to non-depressed (mean = 150 min). In addition, significant increases were observed in sleep latency, REM sleep duration and the number of awakenings. Furthermore, results showed an unexpected high frequency of EEG abnormalities in children with depressive symptoms (75%) characterized by sharp waves and polyspikes in the frontal region. The present results support the notion that depression, in children, is accompanied by changes in sleep patterns, mainly concerning REM sleep. PMID- 17853293 TI - Lamotrigine in motor and mood symptoms of Huntington's disease. AB - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by midlife onset, progressive course and a combination of motor, cognitive and psychiatric symptoms. Since dysregulation of the glutamate/calcium signalling pathway is beginning to emerge as a potential cause of neuron degeneration, antagonists of glutamate pathways such as lamotrigine, may have beneficial value for treatment of HD. We describe the use of lamotrigine in the treatment of an HD patient with motor abnormality (choreoathetoidic movements) complicated by psychiatric abnormalities (depression, severe mood swing and recurrent high risk of suicidal attempts). The patient's depression, severe mood swing and choreoathetoidic movements significantly improved with 300 mg/day of lamotrigine. Experience from our patient suggests that lamotrigine might be effective in treating HD patients with motor and mood symptoms. Further controlled studies are warranted to confirm its efficacy in patients of this type. PMID- 17853294 TI - Olfactory learning prevents MK-801-induced psychosis-like behaviour in an animal model of schizophrenia. AB - There is mounting evidence to support the concept that education is associated with the formation of a functional reserve in the brain, a process that appears to provide some protection against certain aspects of severe central nervous system disorders. The goal of this study was to examine whether learning prevents psychosis-like behaviour in an animal model of schizophrenia. A series of behavioural tasks were used to assess olfactory learning-induced protection against the effects of NMDA channel blocker, MK801. This blocker caused sensory motor disturbances, spatial learning acquisition deficit, and swimming strategy alterations in pseudo-trained and naive rats, but had a considerably lesser effect on trained rats. In sharp contrast, olfactory learning provided no protection against d-amphetamine application. Our data support the notion that learning-induced protection against schizophrenic behaviour is maintained by non NMDA-mediated enhanced activation of local connections in the relevant cortical networks. PMID- 17853295 TI - fMRI amygdala activation during a spontaneous panic attack in a patient with panic disorder. AB - Previous studies on neuronal activation correlates of panic attacks were mostly based on challenge tests, sensory-related stimulation or fear conditioning in healthy subjects. In the present study, we report on a female patient with panic disorder experiencing a spontaneous panic attack under an auditory habituation paradigm in the last stimulation block with sine tones captured with fMRI at 3T. The panic attack was associated with a significantly increased activity in the right amygdala. This is the first report on neuronal activation correlates of a spontaneous panic attack in a patient with panic disorder as measured by fMRI, which lends further support to a pivotal role of the amygdala in the pathogenesis of the disease. PMID- 17853296 TI - A meta-analysis of heart rate and QT interval alteration in anorexia nervosa. AB - OBJECTIVE: Reports have suggested association between sudden death and QT prolongation in AN patients. Incidence and clinical consequences of cardiac abnormalities remain controversial. As the course of AN disease is long-lasting it remains unclear how often psychiatrists should send AN patients for somatic and especially cardiological investigation. The objective of the study was to aggregate the published data on HR and QT alteration and to perform a meta analysis of the HR and QT alteration in patients with anorexia nervosa. METHODS: A Medline search of all English language studies from 1994 to 2005 was performed. The inclusion criteria were confirmed diagnosis of AN, measurement of QTc and mean heart rate. Data from 10 studies were analyzed using weighted linear regression model. RESULTS: Analysis showed that bradycardia and relationship between HR and BMI decreases as the disease continues. QTc interval in AN patients was within normal range although significantly longer than in controls. CONCLUSION: Further investigations of sudden death in patients with AN due to cardiac arrest are needed and a model of clinical monitoring of cardiovascular system should be elaborated. If QTc prolongation is detected even in the normal range further cardiological examination for risk assessment and systematic clinical surveillance of the cardiovascular system should be considered. PMID- 17853297 TI - Complement C4B protein in schizophrenia. AB - Partial and/or complete deficiency of the complement protein C4 is associated with autoimmune and infectious diseases. Infectious or autoimmune processes may have a role in schizophrenia. Previous reports suggest abnormalities in the complement C4B isotype in schizophrenia and other mental disorders. We assessed C4A and C4B isotypes and serum C4B protein concentration in Armenian schizophrenic patients. Although there was no difference in frequency of C4BQ0, C4B serum protein level was significantly decreased in the schizophrenic patients compared with healthy controls. PMID- 17853298 TI - Frontolimbic glutamate alterations in first episode schizophrenia: evidence from a magnetic resonance spectroscopy study. AB - Glutamatergic dysfunction has been implicated in the pathophysiology of schizophrenia. In this study we performed absolute-quantification short-echo magnetic resonance spectroscopy (MRS) in nine patients with first episode schizophrenia and 32 group-matched control subjects to test the hypothesis of glutamatergic dysfunction at disease onset. Regions of interest were the left dorsolateral prefrontal cortex and the left hippocampus. In the patient group absolute concentrations of glutamate were significantly higher in the prefrontal cortex and near-significantly higher in the hippocampus. The glutamate signals significantly correlated with rating scores for schizophreniform symptoms. Absolute-quantification [1H]MRS can reveal glutamatergic abnormalities which might play an important role in the pathogenesis and course of schizophrenia. PMID- 17853299 TI - The 'European Alliance Against Depression (EAAD)': a multifaceted, community based action programme against depression and suicidality. AB - Action programmes fostering partnerships and bringing together regional and national authorities to promote the care of depressed patients are urgently needed. In 2001 the 'Nuremberg Alliance Against Depression' was initiated as a community-based model project within the large-scale 'German Research Network on Depression and Suicidality' (Kompetenznetz 'Depression, Suizidalitat'). The 'Nuremberg Alliance Against Depression' was an action programme, conducted in the city of Nuremberg (500,000 inhabitants) in 2001/2002, addressing four intervention levels (Hegerl et al. Psychol Med 2006;36:1225). Based on the positive results of the Nuremberg project (a significant reduction of suicidal behaviour by more than 20%) 18 international partners representing 16 different European countries established the 'European Alliance Against Depression' (EAAD) in 2004. Based on the four-level approach of the Nuremberg project, all regional partners initiated respective regional intervention programmes addressing depression and suicidality. Evaluation of the activities takes place on regional and international levels. This paper gives a brief overview of the background for and experiences with the EAAD. It describes the components of the programme, provides the rationale for the intervention and outlines the current status of the project. The aim of the paper is to disseminate information about the programme's potential to reduce suicidal behaviour and to provide examples of how European community-based 'best practice' models for improving the care of depressed patients and suicidal persons can be implemented using a bottom-up approach. EAAD is mentioned by the European commission as a best practice example within the Green Paper 'Improving the mental health of the population: Towards a strategy on mental health for the European Union' (European Commission 2005). PMID- 17853300 TI - Investigating the role of the brain-derived neurotrophic factor (BDNF) val66met variant in obsessive-compulsive disorder (OCD). AB - Although evidence from family studies suggest that genetic factors play an important role in mediating obsessive-compulsive disorder (OCD), results from genetic case-control association analyses have been inconsistent. Discrepant findings may be attributed to the lack of phenotypic resolution, and population stratification. The aim of the present study was to investigate the role that the val66met variant within the gene encoding brain-derived neurotrophic factor (BDNF) may play in mediating the development of selected OCD subtypes accounting for the aforementioned confounding factors. One hundred and twelve OCD subjects and 140 controls were selected from the South African Afrikaner population. A significant association was observed in the male subgroup, with the met66 allele implicated as the risk allele in the development of OCD. This allele was also found to be associated with an earlier age at onset of OCD in males. On the other hand, the val66val genotype was associated with more severe OCD in the female population. No evidence of population stratification was observed in Afrikaner control subjects. These preliminary results point towards genetically distinct characteristics of OCD mediated by dysfunctions in BDNF. The present investigation forms part of ongoing research to elucidate the genetic components involved in the aetiology of OCD and OCD-related characteristics. PMID- 17853301 TI - Handedness and schizotypal features in healthy subjects. AB - BACKGROUND: An excess of mixed-handedness has been repeatedly reported in schizophrenia and schizotypy. Handedness is a measure of atypical cerebral lateralization, which is considered as a risk factor for schizophrenia. Several studies have attempted to identify correlations between handedness and dimensions of psychosis but the results obtained so far remain inconclusive. OBJECTIVE: To explore a possible link between mixed-handedness and the three classical dimensions of psychosis. As speech and language disorders may be associated with cerebral lateralization, we predicted a correlation between mixed-handedness and disorganized dimension. METHODS: We used the Schizotypal Personality Questionnaire (SPQ) and the Edinburgh Handedness Inventory (EHI) to study the correlation between mixed-handedness scores and positive, negative or disorganized dimensions in a sample of 62 healthy subjects. RESULTS: We found a negative correlation between mixed-handedness and the disorganized dimension of schizotypy, as individuals with prominent mixed-handedness showed more severe disorganization. CONCLUSION: We have identified a link between mixed-handedness and the disorganized dimension that may help to identify genetic vulnerability factors involved in psychosis. PMID- 17853304 TI - How to position antipsoriatic treatments? PMID- 17853302 TI - Levetiracetam in the treatment of antipsychotics-resistant Tourette syndrome. AB - Levetiracetam, an anti-epileptic agent that enhances GABAergic neurotransmission, is one of the newest alternative treatments of Tourette syndrome (TS). We present the case of a 23-year-old female patient suffering from TS since the age of 7, who exhibited poor response to a variety of agents (haloperidol, pimozide, clonidine and various adjunctive agents) and had four hospitalizations during the previous 2 years due to the deterioration of her clinical state. On her last admission, in addition to clonidine 600 microg/day (already part of her regimen for the previous 4 years), levetiracetam was prescribed, up to 2000 mg/day, progressively titrated over a 3-week period. The patient presented a significant improvement on her TS symptomatology (the score on the Yale Global Tic Severity Scale dropped from 70 at admission, to 25 five weeks later, at discharge), which was preserved during the subsequent 4 months, without any serious side-effect. PMID- 17853305 TI - Calcipotriol cream: a review of its use in the management of psoriasis. AB - Published data are reviewed on the pharmacology, efficacy, tolerability, and pleasantness of the vitamin D(3) analogue calcipotriol in a cream formulation (Daivonex/Dovonex cream; LEO Pharma AS, Denmark) in the treatment of psoriasis. Calcipotriol cream monotherapy is more effective than placebo, and as effective as betamethasone valerate cream and coal tar in psoriasis. A regimen of morning cream and evening-ointment is equally effective as twice-daily calcipotriol ointment and is preferred by patients. Calcipotriol cream is also a highly efficacious maintenance treatment used alone or in an alternating regimen with calcipotriol/betamethasone dipropionate ointment. Short- and long-term trials have demonstrated that calcipotriol cream is well tolerated by patients with psoriasis. Irritation is observed less frequently than with calcipotriol ointment, making the cream very suitable for children and thin or sensitive areas, such as flexures or (off-label use) the face. Calcipotriol cream is generally preferred to the ointment formulation, as shown by preference testing, and leads to improved patient compliance. In conclusion, calcipotriol cream is not only an effective treatment for psoriasis but is pleasant to use and well tolerated even in sensitive areas. Therefore, calcipotriol cream is particularly useful for the maintenance treatment of psoriasis, after induction therapy with a fast-acting vitamin D/steroid two-compound product. PMID- 17853306 TI - Topical pimecrolimus: a new horizon for vitiligo treatment? AB - OBJECTIVES: The purpose of this study was to assess the efficacy of pimecrolimus cream 1% in vitiligo and to evaluate the effects of age of the patients, age of onset and duration of disease on response rate. MATERIALS AND METHODS: Twenty three patients with vitiligo were enrolled in our study; 19 patients (seven male, 12 female) completed the 6-month study period. Patients were treated with topical pimecrolimus 1% cream once daily. The response was evaluated as excellent (76 100%), moderate (51-75%), mild (26-50%), minimal (1-25%), or no response. RESULTS: The mean age of the 19 patients was 29.3+/-16.6 (range 7-62 years) and the mean duration of vitiligo was 68.4+/-81.3 months. Three patients demonstrated an excellent response to the therapy. Four patients had moderate, six patients had mild and five patients had minimal responses; one patient had no response to the treatment. Side effects were noted as a burning and stinging sensation in only three patients. The correlations between response rate and duration of the disease (r = 0.02, p = 0.95), onset age (r = -0.17, p = 0.48), and age of the patients (r = -0.16, p = 0.53) were not significant. CONCLUSIONS: Pimecrolimus has a mild therapeutic effect on vitiligo without significant side effects and can be an alternative therapy agent. PMID- 17853307 TI - Use of etanercept for psoriatic arthritis in the dermatology clinic: the Experience Diagnosing, Understanding Care, and Treatment with Etanercept (EDUCATE) study. AB - OBJECTIVE: To assess the efficacy and tolerability of etanercept to treat psoriatic arthritis. MATERIALS AND METHODS: A total of 1,122 patients who had active psoriatic arthritis were enrolled in a Phase 4, non-randomized, open label, single-arm, 24-week study. These patients had clinically stable, plaque psoriasis involving >or=10% body surface area and joint disease (either >or=two swollen and >or=two tender/painful joints for >or=3 months, or >or=one joint with sacroiliitis or spondylitis). They received etanercept therapy 50 mg subcutaneously once weekly for 24 weeks. RESULTS: After 24 weeks of treatment, 865 patients (77.1%; 95% CI: 74.64-79.55%) achieved a 'mild or better' score on the physician global assessment of psoriasis and were improved from baseline. Mean improvement in body surface area involvement was 16.9 percentage points (15.89-17.91). Patient global assessment of psoriasis, joint pain, and joint disease scores were improved by means of 2.2 (2.15-2.34), 2.7 (2.53-2.84), and 1.5 (1.39-1.55), respectively. Thirty-five patients (3.1%) experienced at least one serious adverse event. No patient died during the study. CONCLUSIONS: These results support the effectiveness and tolerability of etanercept treatment in patients with psoriatic arthritis being treated at dermatology clinics. PMID- 17853308 TI - New-onset, debilitating arthritis in psoriasis patients receiving efalizumab. AB - Efalizumab is a humanized anti-CD11a monoclonal IgG(1) antibody approved for the treatment of moderate-to-severe plaque psoriasis. This case report describes two cases of new-onset debilitating psoriatic arthritis in patients with plaque psoriasis on long-standing efalizumab therapy, despite the fact that their skin disease was in remission. Although during the clinical trials, involving over 2,700 study subjects, arthralgia was seen only at a rate of 1-2% higher than in those subjects receiving placebo, the cases presented here are interesting in that it appears that efalizumab treatment 'uncoupled' the psoriatic arthritic component from the cutaneous disease. It can be speculated that a possible mechanism for efalizumab-induced psoriatic arthritis is related to the blockade of regulatory T cells from joint tissue. PMID- 17853309 TI - High-dose initiation of etanercept in psoriatic arthritis and plaque psoriasis: efficacy, safety and impact on patients' quality of life. AB - BACKGROUND: Etanercept is a human recombinant protein that functions as a competitive inhibitor of tumour necrosis factor-alpha (TNF-alpha), a pro inflammatory molecule exerting a key role in the pathogenesis of psoriatic arthritis (PsA). METHODS: Seventy-one patients affected by PsA with variable skin involvement, refractory to conventional anti-rheumatic drugs, were treated with 50 mg etanercept subcutaneous injections twice-weekly for 12 weeks, followed by a maintenance dose regimen of 25 mg twice-weekly for an additional 12 weeks. Efficacy and safety were assessed at 12-24 weeks. Efficacy criteria was the global assessment of a patient's joint symptoms expressed by the Ritchie index (RI), while skin symptoms were assessed by the psoriasis area and severity index (PASI). The impact of etanercept on patients' quality of life (QoL) was measured by four validated QoL instruments. RESULTS: At week 12, all patients showed a reduction of symptoms with improvement of mean RI (mRI) of 66.1% from baseline and a reduction of mean PASI (mPASI) from 8.8 to 3.2. At week 24, there was a mRI reduction of 78.4% as well as a mPASI reduction to 1.7. Psoriasis-specific QoL measures improved throughout therapy. CONCLUSIONS: A high-dose regimen of etanercept is a highly effective and tolerable treatment for PsA with variable skin involvement, although a larger study population group and a longer trial would be needed to draw strong conclusions about the safety of the higher dose. PMID- 17853310 TI - Do utilization management controls for phototherapy increase the prescription of biologics? AB - The use of phototherapy for psoriasis has declined because of inconvenience, managed care disincentives, and poor reimbursements. However, phototherapy is safer than other options, and the efficacy rates for different methods of phototherapy are among the highest of all available treatment options. Phototherapy is also one of the least costly treatments for moderate-to-severe psoriasis. We hypothesize that utilization management controls on phototherapy shift patients to more expensive and risky systemic treatments. Reducing disincentives on phototherapy will benefit both patients and payors, while increasing physicians' ability to manage this debilitating disease. PMID- 17853311 TI - The added therapeutic efficacy and safety of alefacept in combination with other (systemic) anti-psoriatics in refractory psoriasis. AB - OBJECTIVE: Alefacept is a biologic treatment for psoriasis, with a selective effect on memory effector T cells. Few data are available on the combination of alefacept with either topical or systemic anti-psoriatics. We studied the effect of alefacept combination treatment on clinical disease severity scores and on circulating T-cell subsets. METHODS: Twelve patients with moderate-to-severe psoriasis were included and treated with alefacept for a period of 12 weeks. Patients were allowed to continue the anti-psoriatic therapies they used prior to the study. Severity of disease and expression of T-cell markers CD4, CD8, CD45RA, CD45RO, CD94, CD161, CD25, and CLA were assessed at baseline and after treatment. RESULTS: Seven of 12 included patients used a concomitant systemic therapy: either methotrexate (n = 4), acitretin (n = 2) or cyclosporine (n = 1). PASI reductions in this group after 12 and 24 weeks were 40% and 55%, respectively. Several lymphocyte subsets showed a reduction in circulating numbers. These decreases were independent of the use of an additional systemic psoriasis therapy. CONCLUSIONS: The concomitant use of systemic anti-psoriatic medication in combination with alefacept has a noteworthy impact on efficacy results. No differences in circulating psoriasis-relevant T-cell populations between patients with or without an additional systemic treatment were seen. PMID- 17853312 TI - Treatment of refractory blistering autoimmune diseases with mycophenolic acid. AB - BACKGROUND: Immunosuppressive drugs are used as steroid-sparing agents in the management of blistering autoimmune diseases. Mycophenolic acid (MPA) is a relatively new adjuvant drug that selectively inhibits T and B lymphocyte proliferation by suppressing de novo purine synthesis. OBJECTIVE: To evaluate the efficacy of MPA in refractory blistering autoimmune diseases and the safety profile of a recent formulation, enteric-coated mycophenolate sodium (EC-MPS), in comparison with mycophenolate mofetil (MMF). PATIENTS AND METHODS: Twelve patients with various bullous dermatoses (three pemphigus vulgaris, one pemphigus herpetiformis, three bullous pemphigoid (BP), two cicatricial pemphigoid (CP) and three epidermolysis bullosa acquisita (EBA)) were enrolled in the study. In 10 cases, MPA was administered in combination with systemic corticosteroids, while in two patients with severe diabetes mellitus MPA was employed as monotherapy. The total time on MPA varied from 2 to 8 months. Four patients were given MMF (2,000 mg daily), seven received EC-MPS (1,440 mg daily) and one received both sequentially. RESULTS: Complete remission, lasting for a mean time of 6.1 months, was achieved in 10 patients. Partial remission was obtained in two patients with disseminated CP and EBA. Both MMF and EC-MPS were well tolerated, but the latter was better in terms of gastrointestinal adverse effects. CONCLUSIONS: MPA may be proposed as a first-line adjuvant agent for pemphigus as well as for refractory BP and CP. MPA monotherapy has to be considered in selected cases of BP and pemphigus. The highly promising results obtained in EBA suggest a future key role for MPA in the management of this disease. PMID- 17853313 TI - Disseminated classic Kaposi's sarcoma. Two cases with excellent response to pegylated liposomal doxorubicin. AB - Pegylated liposomal doxorubicin (PLD) is usually used in disseminated HIV-related Kaposi's sarcoma (KS). It is the first-line treatment or second-line therapy in patients who do not tolerate or do not respond to polychemotherapy since 1995, when it was approved by the FDA. We report two cases of disseminated classic KS not associated with immunosuppression in which HHV-8 infection was demonstrated. They showed an excellent response to PLD, with good tolerance and an absence of side effects. PMID- 17853314 TI - Etanercept-induced lichenoid reaction pattern in psoriasis. AB - We describe a patient with severe psoriasis who was treated with 25 mg subcutaneous etanercept, twice weekly, after several traditional topical and systemic treatments had failed. Our patient initially responded well to etanercept, but after 5 weeks she developed remarkable purple, sharply demarcated, erythematosquamous plaques on the dorsa of both hands, wrists and proximal fingers. Histology showed apoptotic cells and basal vacuolization in addition to a histological picture consistent with moderately active psoriasis. Discontinuation of the drug resulted in a slow regression of the eruption. It is important to realize that a lichenoid reaction pattern may occur during anti TNFalpha agent treatment. PMID- 17853315 TI - Polish Registry of Acute Coronary Syndromes (PL-ACS). Characteristics, treatments and outcomes of patients with acute coronary syndromes in Poland. AB - BACKGROUND: In Poland, together with the transformation of the political system, significant positive changes have been made to the national health care system. This provided a possibility for hospitals to apply current standards of care to patients with acute coronary syndromes (ACS). AIM: To assess contemporary data on epidemiology, management and outcomes of patients with ACS in Poland, and to evaluate adherence to the guidelines' recommended treatment. METHODS: We performed an observational study of 100,193 patients hospitalised due to unstable angina, non-ST-segment elevation myocardial infarction (NSTEMI), or ST-segment elevation myocardial infarction (STEMI), prospectively enrolled in 417 hospitals from October 2003 to March 2006 in the ongoing Polish Registry of Acute Coronary Syndromes (PL-ACS). The registry is carried out in cooperation with the Ministry of Health and the National Health Fund. RESULTS: The initial diagnoses were unstable angina in 42.2%, NSTEMI in 26.6%, and STEMI in 31.2% of patients. About one-third of patients were treated outside of cardiology departments (mainly in the internal medicine wards). In patients without ST elevation, invasive strategy (early coronary angiography) was used with almost equal frequency in unstable angina (29.4%) and NSTEMI (31.7%). However, in-hospital mortality was low in unstable angina (0.8%), being much higher in NSTEMI patients (6.6%), (p<0.001). In STEMI reperfusion therapy was administered in 63.3% of patients (thrombolysis 7.8%, primary PCI 54.1%, and PCI after thrombolysis 1.4%). In-hospital mortality in STEMI was 9.3%. Median times from the onset of symptoms to invasive treatment were: 37 hours in unstable angina, 23 hours in NSTEMI, and 5 hours in STEMI. The guidelines' recommended pharmacotherapy was used in a high percentage of patients except for thienopyridines and GP IIb/IIIa inhibitors. CONCLUSIONS: The Polish Registry of Acute Coronary Syndromes shows several discrepancies between guidelines' recommended treatment and their utilisation in everyday practice. Particularly, the under-utilisation of invasive treatment in patients with NSTEMI is alarming. Efforts should be made to increase the usage of invasive treatment in NSTEMI patients and to shorten the delay from the symptom onset to intervention. PMID- 17853316 TI - Pulmonary function test abnormalities in the elderly with systolic heart failure. AB - BACKGROUND: An association between chronic heart failure (CHF) and pulmonary function abnormalities is clinically important. Spirometry is frequently used to evaluate lung function. AIM: To evaluate some spirometric parameters in the elderly with newly diagnosed or known systolic CHF. METHODS: The study group consisted of 110 patients (74 men-67.3%) who underwent echocardiography as well as spirometry with reversibility test. Heart failure was diagnosed using the guidelines of the European Society of Cardiology and Framingham criteria. The average age of the patients was 68.5+/-8.9 years. Smokers constituted 54.5% of the group. Concomitant diseases included arterial hypertension (86.4%), diabetes type 2 (20.9%), and myocardial infarction (49.1%). At the beginning of the study, 54.5% of the patients had already been taking beta-blockers, 84.5% angiotensin converting enzyme inhibitors, 83.6% diuretics, 30% calcium channel blockers, and 92.7% aspirin. Echocardiography revealed left ventricular ejection fraction (LVEF) below 45% in 74 (67.3%) patients. RESULTS: All analysed spirometric parameters were abnormal in CHF patients. A multivariable analysis revealed that age, smoking and LVEF were the only independent parameters which significantly effected FEV1--one of the most important spirometric parameters. CONCLUSIONS: In patients with systolic CHF, independently of the treatment, mixed ventilation disorders were observed, which had a positive reversibility test. Apart from impaired LVEF, older age as well as smoking significantly influenced the deterioration of ventilatory parameters. PMID- 17853317 TI - Analysis of apoptotic markers Fas/FasL (CD95/CD95L) expression on the lymphocytes in patients with acute coronary syndrome. AB - BACKGROUND: Acute coronary syndromes are caused by the rupture or erosion of an atherosclerotic plaque which by secreting a variety of proteases is capable of degrading pericellular matrix components induces death of endothelial cells. This mechanism plays the main role in apoptosis. AIM: To estimate expression of apoptotic Fas/FasL (CD95/CD95L) on lymphocytes in the peripheral blood. METHODS: We examined patients with acute myocardial infarction (n=18, mean age 62+/-8 years), in unstable angina pectoris (n=31, mean age 62+/-10 years) and in a control group (n=20, mean age 62+/-9 years) without coronary risk factors and inflammatory condition. All investigations of Fas/FasL were performed by flow cytometry. Inflammatory parameters and standard risk factors were investigated by standard methods (ELISA). RESULTS: The analysis revealed a higher expression of Fas and FasL molecules on the lymphocytes from patients with acute myocardial infarction (p<0.001, p<0.002) and unstable angina (p<0.01, p<0.02) compared to the control group. Moreover we found a statistically significant positive correlation between the level of LDL cholesterol and hypertension and prevalence of CD95 (p<0.001, p<0.01) and CD95L (p<0.02, p<0.03) in patients with acute myocardial infarction. CONCLUSIONS: A higher expression of apoptotic molecules (Fas and FasL) on lymphocytes occurs before the onset of acute ischaemia and contributes to the plaque rupture and acute coronary syndrome. Furthermore, antiapoptotic therapy leads to plaque stabilisation. PMID- 17853318 TI - Causes of redo procedures in patients with an implantable cardioverter defibrillator--long-term follow-up results. AB - BACKGROUND: Implantation of a cardioverter-defibrillator (ICD) is a well established method to prevent sudden cardiac death (SCD). Due to the expanding indications for this type of treatment and increasing survival of these patients, the ICD population is growing rapidly. AIM: To assess the rate and causes of reoperations in patients with ICD over a long-term (at least 4 years) follow-up period. METHODS: Between 1995 and 2006, an ICD was implanted in 598 patients. This study included all patients with a follow-up duration of at least 4 years and only those who underwent a repeat procedure later than 6 weeks after the index ICD implantation. RESULTS: The study group consisted of 174 patients with a mean age of 51+/-18 years who were followed for a mean of 6+/-1.7 years. Coronary artery disease (CAD) was diagnosed in 92 (53%) patients, and non-ischaemic cardiomyopathy in 82 (47%) patients. Prophylactic ICD therapy was instituted in 11 (6%) patients, whereas 163 (94%) patients received ICD for secondary prophylactics. During the follow-up period, 10 deaths occurred: 6 of all deaths (60%) in patients with CAD and 4 of all deaths (40%) in the non--ischaemic group. A total of 211 redo procedures in 139 patients were performed. Indications for repeat procedures included battery depletion in 136 patients, ICD malfunction in 37 cases, infection related to the implanted system in 5 patients, problems with leads in 19 cases, an upgrade to the dual-chamber system in 5 or to the biventricular system in 3 patients, and the revision of an ICD pocket in 6 patients. CONCLUSIONS: Repeat procedures in ICD recipients are frequent. The most common cause is battery depletion and ICD replacement indicated by a manufacturer. Improvement in ICD technology is essential to increase ICD longevity and decrease the redo-procedure rates. Patients with ICD should be regularly followed in experienced centres in order to detect ICD system failure early. PMID- 17853319 TI - [Congenitally corrected transposition of the great arteries with coexisting stenosis of pulmonary trunk valve and ventricular septum defect in a 55-year-old woman--a case report]. AB - Congenitally corrected transposition of the great arteries (CCTGA) is a rare cardiac malformation. This anomaly is characterised by atrioventricular as well as ventriculoarterial discordance. Isolated CCTGA may cause no symptoms until adult life. Most CCTGA cases with concomitant cardiac abnormalities are symptomatic and are therefore usually diagnosed in childhood. In the majority of patients, congestive heart failure secondary to right ventricular dysfunction occurring by the fifth or sixth decade enables diagnosis. We present an oligosymptomatic 55-year-old woman with corrected transposition of the great arteries and coexisting stenosis of pulmonary trunk valve and ventricular septum defect. PMID- 17853320 TI - [Cardiac arrest with subsequent permanent anoxaemic brain damage in a patient with the Brugada syndrome]. AB - The paper presents a case of a 20-year-old student with a history of cardiac arrest due to ventricular fibrillation. The episode of cardiac arrest occurred when the patient did not complain of any health problems, and there was no visible structural heart disease. Consequently, permanent anoxaemic brain damage was observed. Based on ECG examination, the Brugada syndrome was diagnosed as the cause of cardiac arrest. The ajmaline challenge test was performed in the members of the patient's family. PMID- 17853321 TI - [Catheter malposition in the renal vein--a rare complication related to a peripherally inserted central catheter]. AB - In cardiology intensive care units central venous access is often needed for intravenous infusion of multiple strong acting or hypertonic therapeutic agents such as catecholamines, antibiotics, kalium chloride solutions or parenteral nutrition, as well as for central venous pressure measurements. Currently, access devices include centrally inserted central venous catheters (CVC) and peripherally inserted central venous catheters (PICC). Because of the relative ease of placement, reduced rates of severe complications, such as pneumothorax, great vessel perforation or bleeding, and lower costs in comparison to CVCs, PICCs have been widely used. The PICC has risks, however, with the most frequently occurring complications being catheter malposition followed sometimes by thrombosis, infection or even perforation of the vessel. We present a case of an uncomplicated unsatisfactory location of the catheter tip in the right renal vein, found accidentally during chest angio-CT. Although PICCs are considered to be safe and easy to insert, the proper catheter tip placement is highly unreliable and should be carefully assessed. PMID- 17853322 TI - [Antiplatelet therapy can unmask an inherited bleeding disorder. Aspirin-like defect of platelets does not protect against atherosclerosis]. AB - Some inherited platelet disorders may be revealed late, as in the presented case of a 68-year-old-man. Recurrent epistaxis following peri-interventional antiplatelet therapy (after three elective percutaneous coronary interventions) and an episode of upper gastrointestinal haemorrhage required aspirin withdrawal and less frequent clopidogrel use. Platelet studies showed an aspirin-like defect resulting in a lack of arachidonate-induced platelet aggregation. During dose reduced (2-3 times a week) clopidogrel administration ADP-induced platelet aggregation was effectively inhibited and neither important bleeding nor stent thrombosis occurred. The inherited defect of cyclooxygenase-1, responsible for platelet thromboxane synthesis, did not protect the patient against coronary and extra-cardiac atherosclerosis. PMID- 17853323 TI - [Pulmonary hypertension in patients with systemic sclerosis]. PMID- 17853324 TI - [ECG in a patient with a typical chest pain--normal or abnormal?]. PMID- 17853325 TI - [Left atrial tumour detected during routine echocardiography in a patient with acute myocardial infarction]. PMID- 17853326 TI - [An angioplasty of chronic total occlusion of left anterior descending coronary artery with contralateral visualisation technique]. PMID- 17853327 TI - [Atrioventricular nodal and atrioventricular reentrant tachycardia in a patient with Ebsteinanomaly--the role of percutaneous RF ablation, surgery and Amplatzer septal occluder]. AB - We present a case of a twelve-year-old girl with Ebstein's anomaly, atrial septal defect and two forms of tachycardia. From the first year the patient suffered from episodes of tachycardia. A few months prior to admission, episodes of palpitations became more frequent, periodically incessant and difficult to interrupt, despite amiodarone treatment. During the tachycardia the patient deteriorated with severe cyanosis, hypotension and often with syncope. During sinus rhythm ECG showed RA enlargement and preexcitation. During the documented tachycardia with rate 160-170/min, the ECG showed right bundle branch block (QRS=160 ms) with right axis deviation. An echocardiogram demonstrated dislodgment of septal tricuspid leaflet 30 mm with a high degree of right ventricle atrialisation, moderate tricuspid insufficiency, and ASD with bidirectional shunt. During the EP study two forms of tachycardia were induced: orthodromic atrioventricular reentrant tachycardia, and atrioventricular nodal reentry tachycardia. Both tachycardias were successfully ablated. Four months later the patient underwent TV replacement with aortic homograft, Glenn anastomosis and ASD closure with fenestration. During the next 18 months, the patient was in better general condition, but still was cyanotic especially during exercise (SAT 76%). An Amplatzer occluder was implanted on the 'residual' atrial septal defect. During the 24-month follow-up period, the patients has been in a good general condition, showing good exercise tolerance with no cyanosis or arrhythmia. PMID- 17853328 TI - [Ventricular septal defect closure--importance of cardiac surgery and transcatheter intervention]. PMID- 17853329 TI - The clinical relevance of LDL size and subclasses modulation in patients with type-2 diabetes. AB - Increasing evidence suggest that the "quality" rather than only the "quantity" of low density lipoproteins (LDL) exerts a great influence on the cardiovascular risk. Hypertriglyceridemia, low HDL-cholesterol and increased levels of small dense LDL characterise diabetic dyslipidemia. In subjects with type-2 diabetes LDL size seems also to represent a good marker of clinical apparent and non apparent atherosclerosis. Recently, the Coordinating Committee of the National Cholesterol Education Program stated that high-risk patients may benefit of stronger therapeutical approaches, a category of subjects that include those with type-2 diabetes. Screening for the presence of small, dense LDL may potentially identify those with even higher risk and may contribute in directing specific treatments in order to prevent new cardiovascular events. Hypolipidemic treatments are able to favourably modulate LDL size and subclasses in patients at higher cardiovascular risk. Regarding subjects with type-2 diabetes this seems particularly true for fibrates and less for statins. Analysis of all published studies revealed that atorvastatin represents the most effective agent among statins, while fenofibrate, bezafibrate and gemfibrozil are all very beneficial in modifying LDL size and subclasses towards less atherogenic particles. Nicotinic acid has been found also effective but the extended-release form should be preferred for the reduced intolerance, while fish oils have been shown to be less beneficial. Promising data are also available with the use of ezetimibe, a cholesterol absorption inhibitor. PMID- 17853330 TI - Autoantibodies in diabetes mellitus: current utility and perspectives. AB - Testing of autoantibodies in individuals at risk of developing or being newly diagnosed with diabetes mellitus is currently of very limited clinical value. However, clinical studies evaluating new therapeutic options for the delay or treatment of type 1 diabetes mellitus require sensitive, specific, and reliable assays for autoimmune antibodies associated with diabetes mellitus. With immune modulatory treatment of pre-diabetes mellitus on the horizon the need of reliable assays is evident. In addition, determination of autoimmune antibodies in diabetes mellitus facilitates studies investigating the pathophysiology underlying this disease. Clinicians and researchers should be aware of the tests available, their limitations, their clinical relevance, and their indications. This review focuses on the current knowledge about antibody assays for diabetes associated autoimmunity, their clinical value, their role in diagnosing and predicting autoimmune associated diabetes mellitus, and research applications. PMID- 17853331 TI - High frequency of unrecognized hypoglycaemias in patients with Type 2 diabetes is discovered by continuous glucose monitoring. AB - AIMS: To evaluate the use of a CGMS in the detection of hypoglycaemia in people with type 2 diabetes as an outpatient procedure. METHODS: 31 type 2 diabetic patients underwent glucose monitoring by means of CGMS (Medtronic MiniMed) for up to three days. Patients took part in at least four SMBG (self monitoring blood glucose) tests per day. After three days of monitoring, the CGMS data was downloaded and analysed by a physician to identify the frequency of hypoglycaemias (< or =50 mg/dl) and borderline values (51-70 mg/dl), their duration and distribution. Findings were discussed with the patient and if necessary treatment was adjusted. Eight weeks later, monitoring was repeated to asses the effects of the adjusted treatment. RESULTS: Average duration of sensor wear was 4.19 days. Correlation between the sensor and the SMBG readings was high. A high number of hypoglycaemias and borderline values were detected by the CGMS, most of them unrecognized by the patient. The frequency of hypoglycaemias and borderline values just as the duration could be significantly reduced from first to second monitoring. CONCLUSION: Using the CGMS in type 2 diabetic patients achieved the detection of numerous hypoglycaemias and borderline values both nocturnal and/or unnoticed. The CGMS provides accurate data, which cannot be achieved by conventional SMBG tests. That opens the possibility for treatment adjustment and improvement in metabolic control. For patients it provides a better understanding of the effects of insulin or oral agents, nutrition and exercises to their glucose level. PMID- 17853332 TI - Epidemiology of complications and total treatment costs from diagnosis of Type 2 diabetes in Germany (ROSSO 4). AB - OBJECTIVE: To determine the occurrence of complications and treatment costs in the first 6 years from diagnosis of Type 2 diabetes in the primary care level. DESIGN: The German multi-centre, retrospective epidemiological cohort study ROSSO observed patients from diagnosis in 1995-1999 until the end of 2003 or loss to follow-up. SETTING: 192 randomly contacted primary care practices and all patient records of newly diagnosed type 2 diabetes patients. PARTICIPANTS: All 3,142 patients insured in a public health insurance plan. MAIN OUTCOME MEASURES: Diabetes-related complications were documented from patient files. Treatment costs were attributed using the doctor's tariff, hospital DRGs and medication price lists for Germany. RESULTS: At diagnosis, already 22.4% of patients presented with CHD, 15.4% with CHF, 5.8% with pAOD, 3.1% with stroke and 3.9% with AMI, but less than 0.5% with documented microvascular complications. 7.4% of patients were diagnosed with prior depression and, 5.0% with polyneuropathy. Within a mean of 6.5 years of follow-up 114 patients (3.6%) died. The cumulated occurrence of AMI and stroke rose without a lag phase almost linearly from diagnosis reaching 6.7% for AMI and 7.7% for stroke. The total number of strokes was significantly higher than AMI (181 strokes vs. 109 AMI; p or =5 months) were 1.31 (1.01-1.69) and 1.34 (1.03-1.74), respectively. Familial type 1 diabetes was found more frequently among diabetic than among control children. Higher social status, late introduction of solid food (> or =5 month), and higher current cow's milk consumption (> or =200 ml/d) were associated with a reduced diabetes risk. A considerable proportion of the diabetic risk among preschool children was explained by modifiable exposures. Our findings indicate that infant feeding is causally associated with type 1 diabetes risk and that a considerable part of new type 1 diabetic cases is potentially preventable. PMID- 17853334 TI - Developing effective screening strategies in multiple endocrine neoplasia type 1 (MEN 1) on the basis of clinical and sequencing data of German patients with MEN 1. AB - BACKGROUND: Multiple-endocrine-neoplasia-type-1 (MEN1) is an autosomal-dominant inherited disorder characterized by the combined occurrence of primary hyperparathyroidism (pHPT), gastroenteropancreatic neuroendocrine tumors (GEP), adenomas of the pituitary gland (APA), adrenal cortical tumors (ADR) and other tumors. As the tumors appear in an unpredictable schedule, uncertainty about screening programs is persisting. OBJECTIVE: To optimize screening and to analyze possible differences in sporadic versus familial cases. METHODS: We analyzed data of 419 individuals including 306 MEN-1 patients (138 isolated and168 familial cases out of 102 unrelated families). RESULTS: A total of 683 tumors occurred consisting of 273 pHPT, 138 APA, 166 GEP, 57 ADR, 24 thymic- and bronchial carcinoids as well as 25 neoplasms of other tissues. The age-related penetrance was determined as 10%, 35%, 67%, 81% and 100% at 20, 30, 40, 50 and 65 years respectively. Although pHPT being the most frequent first manifestation (41%), also GEP (22%) or APA (21%) were found to be the first presentation. APA occurred significantly more frequent (p<0,05) in isolated (n=138) than in familial (n=168) cases, whereas GEP showed a tendency to occur more often in familial cases. Genotype/phenotype correlation in 140 clinically affected MEN-1 cases showed a tendency for truncating mutations, especially nonsense mutations to be associated to GEP and carcinoids of the lungs and thymus. CONCLUSION: In view of the morbidity and frequency in familial cases an effective screening programme should aim at an early diagnosis of GEP particularly when truncating, especially nonsense mutations are found. PMID- 17853335 TI - Determination of the aldosterone/renin ratio in 269 patients with adrenal incidentaloma. AB - To determine the prevalence of primary aldosteronism among patients with incidentally discovered adrenal adenomas ('incidentalomas') plasma concentrations of aldosterone (PA) and plasma renin activity (PRA) were determined in 269 patients (100 normotensives, 169 hypertensives) newly referred incidentaloma patients. Among the 100 normotensives a PA [ng/dl]/PRA [ng/ml.h]-ratio (A/R-R) >50 and a concomitant elevation of PA (>15 pg/ml) was initially seen in two cases but further investigations excluded the presence of primary aldosteronism in both patients suggesting a prevalence of primary aldosteronism of <1% among normotensive patients with adrenal incidentaloma. Among the 169 hypertensive incidentaloma patients 14 presented with both, an elevated PA [>15 pg/ml] and an A/R-R >50. Primary aldosteronism was confirmed in 6 of this cases resulting in a prevalence of primary aldosteronism among hypertensive incidentaloma patients of 4%. Although obtained in patients with a supposedly high pre-test probability of primary aldosteronism this percentage--while in keeping with the older literature -is surprisingly low given the recently reported large(r) prevalence of primary aldosteronism among hypertensives in general. PMID- 17853336 TI - Oxidative stress and enzymatic antioxidant status in patients with hypothyroidism before and after treatment. AB - The present study was designed to investigate the relationship between the serum levels of oxidant-antioxidant system (malondialdehyde (MDA) level, Paraoxonase (PON1) activity, nitric oxide (NO) level and superoxide dismutase (SOD) activity) and thyroid hormone status in hypothyroidism pre and posttreatment. The study group comprised 33 patients with primary hypothyroidism. 18 of these patients were reevaluated after euthyroid state i.e. at least 6 months of thyroxine replacement. The patients were compared with 26 normal healthy controls. Serum MDA level, PON1 activity, NO level and SOD activity were measured according to an enzymatic spectrophotometric method. MDA levels were found higher in patients with hypothyroidism before the treatment than the controls. MDA levels were also found to be decreased after the treatment in patients with hypothyroidism. However MDA were found still higher than the controls after the treatment. PON1 activity was found to be lower in patients pretreatment when compared to posttreatment hypothyroidism and controls. Posttreatment of hypothyroidism mean PON1 activity significantly increased compared to pretreatment level but it was still significantly lower than control level. NO level was higher in pretreatment hypothyroidism when compared to controls. SOD activity was not found different in patients before treatment when compared to controls. SOD activity was significantly higher in after treatment when compared to both pretreatment and control levels. In conclusion, increased ROS levels in hypothyroidism may result in a pro-oxidation environment, which in turn could result in decreased antioxidant PON1 activity, increased MDA and NO levels. As a result, lipid peroxidation may have a role in the pathogenesis of the atherosclerosis in hypothyroidism. PMID- 17853337 TI - Pancreatitis in primary hyperparathyroidism-related hypercalcaemia is not associated with mutations in the CASR gene. AB - BACKGROUND: Primary hyperparathyroidism (pHPT) related hypercalcaemia is considered to represent a risk factor for the development of pancreatitis. We therefore explored whether mutations in the calcium-sensing receptor gene ( CASR) coding for the calcium-sensing receptor (CaR), an essential regulator of the calcium homeostasis in parathyroid chief cells, exist in a cohort of patients with pHPT and pancreatitis. METHODS: Among 826 patients prospectively studied between 1987 and 2002 with pHPT, 38 patients were identified with pancreatitis (4.6%). DNA was available of 25 patients (13 females and 12 males). These individuals were analysed for mutations in the CASR by single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. RESULTS: None of the 25 patients with pHPT and pancreatitis carried a CASR mutation and only one had a known heterozygous polymorphism R990G. CONCLUSIONS: Pancreatitis in primary hyperparathyroidism is not associated with mutations in the CASR gene, while it remains to be determined why the polymorphisms A986S, R990G and Q1011E were less often present in that subgroup than in the normal population. PMID- 17853338 TI - Long-lasting subclinical Addison's disease. AB - OBJECTIVE: To report a patient with autoimmune adrenal disease and increased ACTH with longstanding hyperpigmentation as an isolated symptom. METHODS: A 49-year old woman requested a diagnostic work-up for hyperpigmentation initiated 9 years before, associated with increased ACTH. She was receiving replacement therapy for autoimmune hypothyroidism. Basal and dynamic tests of glucocorticoid axis, basal investigation of mineralocorticoid axis and measurement of organ specific autoantibodies were performed. RESULTS: Plasma ACTH (143 pmol/l; normal <13.2 pmol/l) and antibodies against 21-hydroxylase (115 UI/ml; normal <1) were remarkably high, thyroid peroxidase and parietal cell antibodies were positive at low titer and all additional tests were normal. CONCLUSION: Autoimmune adrenal disease can have a very long preclinical period even with high concomitant ACTH and specific antibody titers. PMID- 17853339 TI - Dysphagia due to triple A syndrome: successful treatment of achalasia by balloon dilatation. AB - Triple A syndrome is a rare autosomal recessive inherited disorder which is characterized by alacrima, adrenal insufficiency, and achalasia. We report on a 14-year old girl with dysphagia, regurgitation, and vomiting since 5 years. At the age of five years an Addison crisis was diagnosed and cortisone substitution was initiated. In addition, the patient had episodes of conjunctivitis. Severe esophagitis and candida infection were diagnosed by esophago-gastro-duodenoscopy and treated with omeprazole and fluconazole. The esophageal barium swallow was typical for achalasia. Medical treatment of achalasia with oral nifedipine resulted only in a partial and temporal improvement. But after seven balloon dilatations dysphagia and nocturnal coughing improved clearly and a remarkable gain of weight could be seen. Direct sequencing showed a homozygous nonsense mutation in exon 11 of the AAAS gene leading to truncation at position 342 of the 546 amino acid protein. CONCLUSION: Triple A syndrome has to be considered in patients with dysphagia. In our patient, the absence of tears since birth followed by adrenal insufficiency were early signs of the triple A syndrome. Balloon dilatation of the esophago-gastric junction is an effective treatment, which can avoid surgical interventions. PMID- 17853340 TI - Two rare cases of pituitary metastases from breast and kidney cancers. AB - Pituitary metastases, though very uncommon, may cause endocrine and neurosurgical problems. The clinical manifestation of such metastases is highly variable. Most of the metastatic pituitary tumours are oligosymptomatic. We report two cases of metastatic pituitary lesions. The first patient, a 52-year old female, with metastatic breast cancer, developed symptomatic anterior pituitary insufficiency. The second patient, a 46-years old female presented with signs and symptoms of pituitary apoplexy and visual impairment due to metastasis from renal cancer. None of them was diagnosed with diabetes insipidus, the most common manifestation related to pituitary metastatic mass. PMID- 17853341 TI - Marked hypocalcemia after tocolytic magnesium sulphate therapy. AB - Symptomatic hypocalcemia has been reported infrequently in association with magnesium sulfate (MgSO (4)) tocolytic therapy. We report a 38-year-old woman who presented in preterm labor at 24 3/7 weeks. Twenty hours after starting MgSO (4), she developed chest pain. Studies revealed therapeutic serum Mg level, total serum calcium (Ca) = 5.5 mg/dL, 24-hour urine Ca = 763.9 mg, and low serum uric acid and phosphate levels. All studies corrected day 1 postpartum; urine Ca level corrected on day 2. Even short courses of MgSO (4) can result in severe hypocalcemia, raising the question of whether Ca levels should be routinely monitored. PMID- 17853342 TI - Gastrointestinal presentation of relative adrenal insufficiency in a sick preterm neonate. AB - We report a sick preterm neonate with a dramatic ileus presentation mimicking necrotizing enterocolitis that promptly reversed upon hydrocortisone supplementation. Because our case illustrates a previously unsuspected clinical visage of inadequate adrenal responses in sick preterm neonates, it also emphasizes the need for improved diagnostic algorithms to identify neonates who could potentially benefit from treatment while avoiding the morbid consequences of unwarranted corticosteroids use in this population. PMID- 17853343 TI - The outcome and cumulative morbidity associated with the second and third postcesarean delivery. AB - The purpose of this study was to compare the outcome and cumulative morbidity among women who delivered twice after a cesarean delivery (CD), and who underwent in the second delivery either a trial of labor (TOL) or planned cesarean delivery (PCD). Eligible women (N = 399) were divided into two groups based on first post CD: a TOL (n = 304) or PCD (n = 95). Women attempting a TOL were successful in 70 and 75% in the first and second post-CD, respectively. All participants undergoing a PCD subsequently had a third PCD. The overall morbidity was 8.4 and 5.3% among PCD and TOL groups, respectively ( P = 0.258). Women attempting a TOL after a previous CD had a 70 and 53% likelihood for at least one successful or two successful vaginal births in the two subsequent deliveries, respectively. No significant difference was documented between the groups regarding the cumulative morbidity. PMID- 17853344 TI - Expression of calcitonin gene-related peptide-receptor component protein (CGRP RCP) in human myometrium in differing physiological states and following misoprostol administration. AB - Our objective was to assess relative expression levels of mRNA for calcitonin gene-related peptide-receptor component protein (CGRP-RCP) in human myometrium in various physiological states. Using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), we analyzed myometrial samples from 46 women (10 menopausal, 10 nongravid premenopausal, 19 gravidae, and 7 premenopausal misoprostol-treated nongravid women) for the specific expression of CGRP-RCP mRNA. The expression of CGRP-RCP was significantly increased in gravid compared with nongravid myometrium ( P < 0.002). No significant differences in CGRP-RCP expression were found among the other study groups. We concluded that the increased mRNA expression CGRP-RCP in gravid myometrium supports the possibility of involvement of CGRP in the control of myometrial contractility. Additional studies are necessary to evaluate the exact mechanism of action of CGRP and CGRP RCP in human myometrium. PMID- 17853345 TI - Eremophilane-type sesquiterpenes from Senecio nemorensis. AB - Three new highly oxygenated eremophilane-type sesquiterpenes, 1 beta,10 beta(8,12)-diepoxy-7 beta,11 beta-dihydroxy-8 beta,12 alpha-dimethoxyeremophilane (1), 1 beta,10 beta-epoxy-7 beta-hydroxy-8 alpha-methoxyeremophil-11 alphaH-12,8 beta-olide (2), and 6 beta-isobutyryloxy-8 alpha-hydroxy-1-oxoeremophil-7(11),9 dien-12,8 beta-olide (3), together with nine known compounds (4-12) were isolated from the roots and aerial parts of Senecio nemorensis L. (Compositae). Structures of compounds 1-3 were elucidated on the basis of spectroscopic evidence including IR, HR-ESI-MS, 1D and 2D NMR techniques and were unequivocally confirmed by single-crystal X-ray diffraction experiments. The antimicrobial activity of the isolated compounds 1-3 and 8-12 was tested against Staphylococcus aureus and Candida albicans. PMID- 17853346 TI - Reverse pharmacognosy: identifying biological properties for plants by means of their molecule constituents: application to meranzin. AB - Reverse pharmacognosy aims at finding biological targets for natural compounds by virtual or real screening and identifying natural resources that contain the active molecules. We report herein a study focused on the identification of biological properties of meranzin, a major component isolated from Limnocitrus littoralis (Miq.) Swingle. Selnergy, an IN SILICO biological profiling software, was used to identify putative binding targets of meranzin. Among the 400 screened proteins, 3 targets were selected: COX1, COX2 and PPARgamma. Binding tests were realised for these 3 protein candidates, as well as two negative controls. The predictions made by Selnergy were consistent with the experimental results, meaning that these 3 targets can be modulated by an extract containing this compound in a suitable concentration. These results demonstrate that reverse pharmacognosy and its inverse docking component is a powerful tool to identify biological properties for natural molecules and hence for plants containing these compounds. PMID- 17853347 TI - [Certified continuing medical education in print media 2007: a situation analysis]. PMID- 17853348 TI - [Symptomatic treatment of dyspnoea in patients receiving palliative care: nasal delivery of oxygen compared with opioid administration]. AB - BACKGROUND AND OBJECTIVE: Dyspnoea frequently occurs in patients with advanced tumor disease receiving palliative care (prevalence > 50). Aim of the study was to assess, in dyspneic patients in palliative care, the efficacy of opioids in treating their dyspnoea and to determine whether or not nasal administration of oxygen previous to opioid administration would decrease the severity of dyspnoea. PATIENTS AND METHODS: In a prospective, non-randomised study 25 patients with cancer who had been admitted to our palliative care unit were investigated (aged 64.5 +/- 15.1 [40-90] years; 11 males [44 %]. 13 patients reported severe and 12 moderate dyspnoea. For symptomatic treatment of dyspnoea, 12 patients received morphine and 13 patients hydromorphine. The severity of of dyspnoea was rated according to a numeric scale (NRS 0-10). Recorded and compared was severity of dyspnoea at admission before any oxygen had been administered, after 30 minutes of nasal oxygen, and 30, 60, 90 and 120 minutes after the first administration of opioid without nasal oxygen. RESULTS: Whereas there was no change in the severity of dyspnoea during nasal oxygen administration, mean respiratory rate (f) 30 minutes after the first opioid application had significantly decreased. The intensity of dyspnoea had significantly diminished 90 minutes after the first opioid application. CONCLUSION: During nasal oxygen administration the severity of dyspnoea, as measured by use of NRS had not decreased, whereas it had significantly decreased after the first opioid administration. PMID- 17853349 TI - [Successful therapy of patients in therapy-resistant cardiogenic shock with intracoronary, autologous bone marrow stem cell transplantation]. AB - HISTORY AND CLINICAL FINDINGS: A 64-year-old man with known coronary 3-vessel disease (CAD) who had sustained an anterior myocardial infarction 14 years ago was admitted with signs of acute left heart failure associated with another anterior myocardial infarction. INVESTIGATIONS: The electrocardiogram (ECG) showed ST-segment elevation from V1 to V6. Creatine kinase, troponin I and lactate dehydrogenase levels were elevated. DIAGNOSIS: Emergency cardiac catheterization revealed a coronary 3-vessel disease with severe stenosis in left anterior descending coronary artery (LAD). Left ventricular angiography demonstrated severe impairment of left ventricular contractile function with akinesia of the entire anterior wall of the left ventricle. TREATMENT AND COURSE: Coronary angioplasty and stent implantations of the LAD were undertaken, but cardiogenic shock occurred requiring intubation, ventilation and intraaortic counterpulsation (IABP). It was possible to discontinue the latter after two days, but the cardiogenic shock persisted for six weeks, requiring increasing amounts of catecholamines and high inspiratory ventilation pressure (max Pinsp) and high positive end-expiratory wedge pressure (PCW). Nine days after autologous adult bone marrow derived stem cell injection into the right and left coronary artery, the left ventricular function gradually improved and the catecholamine amount gradually reduced. It was then possible to extubate the patient and transfer him to a general ward. Angiocardiography after one month demonstrated an increase of the ejection fraction from 17% to 28% and good coronary blood flow in the LAD. CONCLUSIONS: Intracoronary transplantation of adult autologous bone marrow stem cells achieved safe and efficacious regeneration of ischemic and infarcted myocardium. It can be assumed that myocardial repair was associated with the stem cell transplantation and/or cytokine action. The intracoronary stem cell transplantation may reduce the mortality of otherwise treatment-resistant cardiogenic shock. PMID- 17853350 TI - [Intramural hematoma of the left common carotid artery]. PMID- 17853351 TI - [Pharmacotherapy of colon cancer]. PMID- 17853352 TI - [Genetics of cerebral cavernous malformations (CCM)]. PMID- 17853353 TI - [Issuance of X-ray plates to patients for inspection. Decision of the Kiel District Court from March 30, 2007]. PMID- 17853354 TI - When plant life gets tough sulfur gets going. PMID- 17853355 TI - Sulfate assimilation in basal land plants - what does genomic sequencing tell us? AB - Sulfate assimilation is a pathway providing reduced sulfur for the synthesis of cysteine, methionine, co-enzymes such as iron-sulfur centres, thiamine, lipoic acid, or Coenzyme A, and many secondary metabolites, e.g., glucosinolates or alliins. The pathway is relatively well understood in flowering plants, but very little information exists on sulfate assimilation in basal land plants. Since the finding of a putative 3'-phosphoadenosine 5'-phosphosulfate reductase in PHYSCOMITRELLA PATENS, an enigmatic enzyme thought to exist in fungi and some bacteria only, it has been evident that sulfur metabolism in lower plants may substantially differ from seed plant models. The genomic sequencing of two basal plant species, the Bryophyte PHYSCOMITRELLA PATENS, and the Lycophyte SELAGINELLA MOELLENDORFFII, opens up the possibility to search for differences between lower and higher plants at the genomic level. Here we describe the similarities and differences in the organisation of the sulfate assimilation pathway between basal and advanced land plants derived from genome comparisons of these two species with ARABIDOPSIS THALIANA and ORYZA SATIVA, two seed plants with sequenced genomes. We found differences in the number of genes encoding sulfate transporters, adenosine 5'-phosphosulfate reductase, and sulfite reductase between the lower and higher plants. The consequences for regulation of the pathway and evolution of sulfate assimilation in plants are discussed. PMID- 17853356 TI - Novel insight into the regulation of GSH biosynthesis in higher plants. AB - In higher plants, the redox-active tripeptide glutathione (GSH) fulfills a plethora of functions. These include its pivotal role for maintaining the cellular redox poise and its involvement in detoxification of heavy metals and xenobiotics. Intimately linked to these functions, GSH also acts as a cellular signal, mediating control of enzyme and/or regulatory protein activities, either directly or via glutaredoxins. The redox potential of the GSH/GSSG couple is not only affected by the GSH/GSSG ratio but also by changes in GSH synthesis and/or degradation. As this couple operates as redox buffer in several cellular compartments, the regulation of GSH biosynthesis and transport (both intra- and intercellularly) are fundamental to the maintenance of cellular redox homeostasis during plant development and, even more so, when plants are exposed to biotic or abiotic stress. This review highlights novel aspects of GSH biosynthesis and transport with a focus on the regulation of the GSH1 (= gamma-glutamylcysteine synthetase) enzyme. Interestingly, GSH1 appears to be exclusively confined to the plastids, whereas the second biosynthetic enzyme, GSH2, is predominantly localized in the cytosol. GSH1 expression and enzyme activity are under multiple controls, extending from transcriptional regulation to post-translational redox control. Now that the plant GSH1 protein structure has been solved, the molecular basis of GSH1 function and redox regulation can be addressed. The review concludes with a discussion of the simultaneous changes observed for GSH synthesis, transport, and metabolism during Cd-induced phytochelatin accumulation. PMID- 17853357 TI - The effect of sulfur nutrition on plant glucosinolate content: physiology and molecular mechanisms. AB - Glucosinolates are sulfur-rich plant metabolites of the order Brassicales that function in the defense of plants against pests and pathogens. They are also important in human society as flavor components, cancer-prevention agents, and crop biofumigants. Since glucosinolates may represent up to 30 % of the total sulfur content of plant organs, their accumulation should depend intimately on the sulfur status of the entire plant. Here we review the literature on how sulfur supply affects glucosinolate content. In field and greenhouse experiments involving soil, hydroponic and tissue culture media, sulfur fertilisation usually led to an increase in glucosinolate content ranging from 25 % to more than 50 fold, depending on the plant species, amount of sulfur applied, and type of treatment. The effect was greater on glucosinolates derived from the sulfur amino acid, methionine, than on glucosinolates derived from tryptophan. These changes are regulated not by simple mass action effects, but by extensive changes in gene transcription. In sulfur-deficient plants, there is a general down-regulation of glucosinolate biosynthetic genes which accompanies an up-regulation of genes controlling sulfur uptake and assimilation. Glucosinolates may be considered a potential source of sulfur for other metabolic processes under low-sulfur conditions, since increased breakdown of glucosinolates has been reported under sulfur deficiency. However, the pathway for sulfur mobilisation from glucosinolates has not been determined. The breakdown of indolic glucosinolates to form auxin in roots under sulfur-deficient conditions may help stimulate root formation for sulfur uptake. PMID- 17853358 TI - Characterization of cysteine-degrading and H2S-releasing enzymes of higher plants - from the field to the test tube and back. AB - Due to the clean air acts and subsequent reduction of emission of gaseous sulfur compounds sulfur deficiency became one of the major nutrient disorders in Northern Europe. Typical sulfur deficiency symptoms can be diagnosed. Especially plants of the Cruciferae family are more susceptible against pathogen attack. Sulfur fertilization can in part recover or even increase resistance against pathogens in comparison to sulfur-deficient plants. The term sulfur-induced resistance (SIR) was introduced, however, the molecular basis for SIR is largely unknown. There are several sulfur-containing compounds in plants which might be involved in SIR, such as high levels of thiols, glucosinolates, cysteine-rich proteins, phytoalexins, elemental sulfur, or H2S. Probably more than one strategy is used by plants. Species- or even variety-dependent differences in the development of SIR are probably used. Our research focussed mainly on the release of H2S as defence strategy. In field experiments using different BRASSICA NAPUS genotypes it was shown that the genetic differences among BRASSICA genotypes lead to differences in sulfur content and L-cysteine desulfhydrase activity. Another field experiment demonstrated that sulfur supply and infection with PYRENOPEZIZA BRASSICA influenced L-cysteine desulfhydrase activity in BRASSICA NAPUS. Cysteine degrading enzymes such as cysteine desulfhydrases are hypothesized to be involved in H2S release. Several L- and D-cysteine-specific desulfhydrase candidates have been isolated and partially analyzed from the model plant ARABIDOPSIS THALIANA. However, it cannot be excluded that H2S is also released in a partial back reaction of O-acetyl-L-serine(thiol)lyase or enzymes not yet characterized. For the exact determination of the H2S concentration in the cell a H2S-specific microsensor was used the first time for plant cells. The transfer of the results obtained for application back on BRASSICA was initiated. PMID- 17853359 TI - Significance of plant sulfite oxidase. AB - Sulfite oxidizing activities are known since years in animals, microorganisms, and also plants. Among plants, the only enzyme well characterized on molecular and biochemical level is the molybdoenzyme sulfite oxidase (SO). It oxidizes sulfite using molecular oxygen as electron acceptor, leading to the production of sulfate and hydrogen peroxide. The latter reaction product seems to be the reason why plant SO is localized in peroxisomes, because peroxisomal catalase is able to decompose hydrogen peroxide. On the other hand, we have indications for an additional reaction taking place in peroxisomes: sulfite can be nonenzymatically oxidized by hydrogen peroxide. This will promote the detoxification of hydrogen peroxide especially in the case of high amounts of sulfite. Hence we assume that SO could possibly serve as "safety valve" for detoxifying excess amounts of sulfite and protecting the cell from sulfitolysis. Supportive evidence for this assumption comes from experiments where we fumigated transgenic poplar plants overexpressing ARABIDOPSIS SO with SO(2) gas. In this paper, we try to explain sulfite oxidation in its co-regulation with sulfate assimilation and summarize other sulfite oxidizing activities described in plants. Finally we discuss the importance of sulfite detoxification in plants. PMID- 17853360 TI - Facts and fiction about sulfur metabolism in relation to plant-pathogen interactions. AB - Sulfur deficiency developed into a widespread nutrient disorder in the 1980s because of the drastic decrease of SO(2) emissions in western Europe after Clean Air Acts came into force. It was observed that not only the yield and quality of agricultural crops were negatively affected by sulfur deficiency but also their health status. Since the mid 1990s the physiological background of this latter phenomenon in the sulfur metabolism has been studied by different researchers. From 2001 until 2006, field trials with different varieties of oilseed rape were conducted in Germany, and also from 2001 until 2003 in Scotland, to investigate the underlying mechanisms of sulfur-induced resistance and to develop fertiliser strategies which increase the health status of crops and minimise the requirement for chemical fungicides. A comprehensive disease assessment was conducted and a range of different sulfur-containing metabolites and enzymes were analysed in relation to sulfur nutrition and fungal diseases. H2S emissions from field-grown crops under different sulfur nutritional status were studied for the first time and a positive relationship was observed. Besides S fertilisation, fungal infection increased H2S emissions, too. The studies deliver new insight into the complex of sulfur-induced resistance but many questions still remain open. This contribution will show different possible strategies to solve some of the open questions. PMID- 17853361 TI - Sulfur-enhanced defence: effects of sulfur metabolism, nitrogen supply, and pathogen lifestyle. AB - Evidence from field experiments indicates differential roles of sulfur and nitrogen supply for plant resistance against pathogens. Dissection of these observations in defined pathosystems and controlled nutritional conditions indicates an activation of plant sulfur metabolism in several incompatible and compatible interactions. Contents of cysteine and glutathione as markers of primary sulfate assimilation and stress response show increases in ARABIDOPSIS THALIANA upon infection, coinciding with the synthesis of sulfur-containing defence compounds. Similar increases of thiols were observed with necrotrophic, biotrophic, and hemibiotrophic pathogens. Sulfate supply was found to be neutral or beneficial for tolerance against fungal but neutral for bacterial pathogens under IN VITRO conditions. According to various reports and own observations the effects of nitrogen supply appeared to be neutral or harmful, depending on the pathogen. The activation of sulfur metabolism was a consequence of activation of gene expression as revealed by macroarray analysis of an A. THALIANA/ALTERNARIA BRASSICICOLA pathosystem. This activation appeared to be largely independent from sufficient or optimal sulfate supply and from the established sulfate deficiency response. The data suggest that plant-pathogen interactions and sulfur metabolism are linked by jasmonic acid as signal. PMID- 17853362 TI - Sulfur metabolism in plants: are trees different? AB - Sulfur metabolite levels and sulfur metabolism have been studied in a significant number of herbaceous and woody plant species. However, only a limited number of datasets are comparable and can be used to identify similarities and differences between these two groups of plants. From these data, it appears that large differences in sulfur metabolite levels, as well as the genetic organization of sulfate assimilation and metabolism do not exist between herbaceous plants and trees. The general response of sulfur metabolism to internal and/or external stimuli, such as oxidative stress, seems to be conserved between the two groups of plants. Thus, it can be expected that, generally, the molecular mechanisms of regulation of sulfur metabolism will also be similar. However, significant differences have been found in fine tuning of the regulation of sulfur metabolism and in developmental regulation of sulfur metabolite levels. It seems that the homeostasis of sulfur metabolism in trees is more robust than in herbaceous plants and a greater change in conditions is necessary to initiate a response in trees. This view is consistent with the requirement for highly flexible defence strategies in woody plant species as a consequence of longevity. In addition, seasonal growth of perennial plants exerts changes in sulfur metabolite levels and regulation that currently are not understood. In this review, similarities and differences in sulfur metabolite levels, sulfur assimilation and its regulation are characterized and future areas of research are identified. PMID- 17853363 TI - Interaction of sulfur and nitrogen nutrition in tobacco (Nicotiana tabacum) plants: significance of nitrogen source and root nitrate reductase. AB - The significance of root nitrate reductase for sulfur assimilation was studied in tobacco (NICOTIANA TABACUM) plants. For this purpose, uptake, assimilation, and long-distance transport of sulfur were compared between wild-type tobacco and transformants lacking root nitrate reductase, cultivated either with nitrate or with ammonium nitrate. A recently developed empirical model of plant internal nitrogen cycling was adapted to sulfur and applied to characterise whole plant sulfur relations in wild-type tobacco and the transformant. Both transformation and nitrogen nutrition strongly affected sulfur pools and sulfur fluxes. Transformation decreased the rate of sulfate uptake in nitrate-grown plants and root sulfate and total sulfur contents in root biomass, irrespective of N nutrition. Nevertheless, glutathione levels were enhanced in the roots of transformed plants. This may be a consequence of enhanced APR activity in the leaves that also resulted in enhanced organic sulfur content in the leaves of the tranformants. The lack of nitrate reductase in the roots in the transformants caused regulatory changes in sulfur metabolism that resembled those observed under nitrogen deficiency. Nitrate nutrition reduced total sulfur content and all the major fractions analysed in the leaves, but not in the roots, compared to ammonium nitrate supply. The enhanced organic sulfur and glutathione levels in ammonium nitrate-fed plants corresponded well to elevated APR activity. But foliar sulfate contents also increased due to decreased re-allocation of sulfate into the phloem of ammonium nitrate-fed plants. Further studies will elucidate whether this decrease is achieved by downregulation of a specific sulfate transporter in vascular tissues. PMID- 17853364 TI - Leaf developmental stage affects sulfate depletion and specific sulfate transporter expression during sulfur deprivation in Brassica napus L. AB - BRASSICA NAPUS was grown under hydroponic conditions and responses to the removal of the external supply of sulfur (S) were analysed in roots and in leaves of different developmental age. The concentrations of sulfate and nitrate were greatest in the older leaves and least in younger leaves, whilst phosphate was greatest in roots and youngest leaves and least in old leaves. S-deprivation resulted in decreases in tissue sulfate concentrations at variable rates in the order: roots and young leaves > middle-aged leaves > oldest leaves. Phosphate concentrations were unaffected and nitrate concentrations were only depleted in the oldest leaves. Expression of representative members of the sulfate transporter gene family was assessed by Northern blotting in the respective tissues. Group 1 transporters (high affinity type) were induced in response to S deprivation in all tissues except old leaves, where no expression was detected, and to the greatest extent in roots. Groups 2 and 5 (a BRASSICA Group 5 sulfate transporter is reported here, accession number: AJ311389) transporters showed either no or only a small induction by S-deprivation. Group 4 transporters (localised in the tonoplast membrane and thought to be involved in vacuolar sulfate efflux) were induced by S-deprivation with a complex pattern: 4;1 was expressed in root and mature leaves, was strongly induced by sulfur-deprivation in roots, and was also induced in the middle-aged leaves alone; 4;2 was only expressed under S-deprivation in parallel with the observed pattern of tissue sulfate concentrations. Expression patterns indicated that both differences in intracellular sulfate pools and localised aspects of the signal transduction pathway link tissue sulfate-status and sulfur-nutrition regulated gene expression. PMID- 17853365 TI - The characteristic high sulfate content in Brassica oleracea is controlled by the expression and activity of sulfate transporters. AB - The uptake and distribution of sulfate in BRASSICA OLERACEA, a species characterised by its high sulfate content in root and shoot, are coordinated and adjusted to the sulfur requirement for growth, even at external sulfate concentrations close to the K (m) value of the high-affinity sulfate transporters. Plants were able to grow normally and maintain a high sulfur content when grown at 5 or 10 microM sulfate in the root environment. Abundance of mRNAs for the high affinity sulfate transporters, BolSultr1;1 and BolSultr1;2, were enhanced at 0.99 for all components) and recovery (>85% for all components). The detection and quantitation limits for barbaloin were determined to be 0.02 and 0.1 ppm at signal-to-noise ratios of approximately 3:1 and 10:1, respectively. PMID- 17853382 TI - Simultaneous determination of cinnamaldehyde, eugenol and piperine by HPTLC densitometric method. AB - An HPTLC densitometric method for the simultaneous determination of cinnamaldehyde and eugenol as well as trace amounts of piperine in pepper contaminated cinnamon was developed. The applicability of the method was tested with cinnamon bark powder adulterated with pepper powder, cinnamon oil, clove powder, clove oil and a commercial preparation containing cinnamaldehyde and eugenol. The method was validated for specificity, precision, accuracy and robustness. The method was found to be precise for different concentrations of cinnamaldehyde, eugenol and piperine. The accuracy of the method was checked by conducting a recovery study at three different levels. The linearity was found to be in the ranges 52.54-735.56, 533.2-8531.2 and 50-300 ng/spot, respectively, with correlation coefficients of 0.9985 +/- 0.04, 0.9982 +/- 0.06 and 0.9937 +/- 0.11 for cinnamaldehyde, eugenol and piperine. PMID- 17853383 TI - Studies on the stability of diester-diterpenoid alkaloids from the genus Aconitum L. by high performance liquid chromatography combined with electrospray ionisation tandem mass spectrometry (HPLC/ESI/MSn). AB - The stability of diester-diterpenoid alkaloids (DDA) from plants of the genus Aconitum L. has been studied in different solvents and pH buffers. The HPLC/ESIMS method for analysing the concentration of DDA was established and DDA's decomposition products were elucidated by HPLC/ESI-MS/MS(n). In different solvents, e.g. dichloromethane, ether, methanol and distilled water, the decomposition pathways of DDA are quite different and their difference in stabilities depends on the difference of their structures, in which substituents at the N atom and substituents at C-3 are different. The pyrolytic products of DDA, such as deacetoxy aconitine-type alkaloids, have been observed in the above solvents, whereas 8-methoxy-14-benzoyl aconitine-type alkaloids have been obtained only in methanol. Furthermore, the experimental results demonstrate that the stability of DDA depends on pH values of the buffer. Aconine as hydrolysate has been only found in pH 10.0 buffer, and the other hydrolysates and the pyrolyzates of DDA, such as benzoylaconine and deacetoxy aconitine, have been observed in all pH aqueous solutions. The decomposition pathways of DDA in buffers are related to the substituent on the C-3 position. The decomposition pathway of aconitine is similar to that of mesaconitine, but different from that of hypaconitine. PMID- 17853384 TI - Assessing non-inferiority of a new treatment in a three-arm trial in the presence of heteroscedasticity. AB - In this paper, we describe an adjusted method to facilitate non-inferiority tests in a three-arm design. While the methodology is readily available in the situation of homogeneous group variances, the adjusted method will also maintain the alpha-level in the presence of heteroscedasticity. We propose explicit criteria for an optimal allocation. Depending on the pattern of heterogeneity, remarkably unbalanced designs are power optimal. We will apply the method to a randomized clinical trial and a toxicological experiment. PMID- 17853385 TI - Simultaneous determination of swertiamarin and its metabolites (5Z)-5-ethylidene 8-hydroxy-3,4,5,6,7,8-hexahydro-1H-pyrano[3,4-c]pyridin-1-one and erythrocentaurin in broth of Aspergillus niger by HPLC. AB - When cultivated with Aspergillus niger, swertiamarin, an important drug, is rapidly transformed into erythrocentaurin and (5Z)-5-ethylidene-8-hydroxy 3,4,5,6,7,8-hexahydro-1H-pyrano[3,4-c]pyridin-1-one (M(1)), a new compound with high anti-inflammatory activity. A simple and rapid HPLC method for simultaneous determination of swertiamarin and its two metabolites in broth of A. niger is described. The chromatographic separation was achieved on a C(18) ODS column (250 x 4.6 mm i.d.) by gradient elution with 0.04% formic acid in water and 0.04% formic acid in acetonitrile as the gradient mixtures. The flow rate was 1 mL/min, the detection wavelength was 237 nm and the column temperature was kept at 30 degrees C. The retention times of swertiamarin, erythrocentaurin and M(1) were 14.6, 16.8 and 24.8 min, respectively. The mean absolute recoveries of three analysts were over 96%. Quantification limits were 0.02 microg/mL for swertiamarin and 0.05 microg/mL for both of the two metabolites. The method was applied for the quantification of swertiamarin and its two metabolites during the fermentation process and the evaluation of the bioavailabilities in the Caco-2 monolayer. PMID- 17853386 TI - Simultaneous determination of harpagoside and cinnamic acid in rat plasma by liquid chromatography electrospray ionization mass spectrometry and its application to pharmacokinetic studies. AB - A simple and sensitive method was developed for the simultaneous quantification of harpagoside and cinnamic acid in rat plasma using high-performance liquid chromatography system coupled to a negative ion electrospray mass spectrometric analysis. The plasma sample preparation was a simple deproteinization by the addition of two volumes of acetonitrile. The analytes were separated on an Intersil C8-3 column (2.1 mm i.d.x250 mm, 5 microm) with acetonitrile-5 mm ammonium formate aqueous solution (60:40, v/v) as mobile phase at a flow-rate of 0.2 mL/min. Detection was performed on a quadrupole mass spectrometer equipped with electrospray ionization (ESI) source operated under selected ion monitoring (SIM) mode. [M+HCOO]- at m/z 539 for harpagoside, [M-H]- at m/z 147 for cinnamic acid and [M-H]- at m/z 137 for salylic acid (internal standard) were selected as detecting ions, respectively. The method was validated over the concentration range 7-250 ng/mL for harpagoside and 5-500 ng/mL for cinnamic acid. The lower limits of quantitation for harpagoside and cinnamic acid were 7 and 5 ng/mL, respectively. The intra- and inter-day precisions (RSD%) were within 9.5% and the assay accuracies (RE%) ranged from -5.3 to 3.0% for both analytes. Their average recoveries were greater than 86%. Both analytes were proved to be stable during all sample storage, preparation and analysis procedures. The method was successfully applied to the pharmacokinetic study of harpagoside and cinnamic acid following oral administration of Radix Scrophulariae extract to rats. PMID- 17853387 TI - Round-robin evaluation of a solid-phase microextraction-gas chromatographic method for reliable determination of trace level ethylene oxide in sterilized medical devices. AB - Medical devices that are sterilized with ethylene oxide (EtO) retain small quantities of EtO residuals, which may cause negative systemic and local irritating effects, and must be accurately quantified to ensure non-toxicity. The goal of this round-robin study is to investigate the capability of a novel solid phase microextraction-gas chromatographic (SPME-GC) method for trace-level EtO residuals analysis: three independent laboratories conducted a guided experiment using this SPME-GC method, in assessing method performance, ruggedness and the feasibility of SPME fibers. These were satisfactory across the independent laboratories, at the 0.05-5.00 ppm EtO range. This method was then successfully applied to analyze EtO residuals in several sterilized/aerated medical devices of various polymeric composition, reliably detecting and quantifying the trace levels of EtO residuals present ( approximately 0.05 ppm EtO). SPME is a feasible alternative for quantifying trace-level EtO residuals in sterilized medical devices, thereby lowering the limit of quantification (LOQ) by as much as two to three orders of magnitude over the current GC methodology of direct liquid injection. PMID- 17853388 TI - Screening and identification of potential bioactive components in a combined prescription of Danggui Buxue decoction using cell extraction coupled with high performance liquid chromatography. AB - A cell extraction coupled with high-performance liquid chromatography (HPLC) analysis has been developed to screen the potential bioactive components in combined prescription of Danggui Buxue decoction. The method was validated by using HL-7702 cells, RAW 264.7 cells and Caco-2 cell extraction. According to the hypothesis that, when cells are incubated together with the extract of traditional Chinese medicines (TCMs), the potential bioactive compounds in the extract should selectively combine with the cells, cell-combining compounds were analyzed by HPLC-diode array-evaporative light scattering detectors. Their structures were elucidated in comparison with available reference compounds, and further confirmed by HPLC-electrospray ionization time-of-flight mass spectrometry with accurate mass measurement. The results demonstrated that nine compounds were combined with the HL-7702 cells, seven with RAW 264.7 cells, and thirteen with the Caco-2 cell line. In view of the two key steps of drugs action, absorption by intestinal epithelium cells and interaction with target cells, this rapid and reliable method could be utilized to predict the bioactive constituents in TCMs, and it was in agreement with the characteristics of combined prescriptions of TCMs as multi-components, multi-target sites and multi-channel actions. PMID- 17853389 TI - Determination of fifteen bioactive components in Radix et Rhizoma Salviae Miltiorrhizae by high-performance liquid chromatography with ultraviolet and mass spectrometric detection. AB - A high-performance liquid chromatographic (HPLC) method coupled with ultraviolet (UV) and electrospray ionization time-of-flight mass spectrometry (ESI-TOF/MS) was established for simultaneous qualitative and quantitative determination of nine phenolic acids and six diterpenoids in Radix et Rhizoma Salviae Miltiorrhizae (RRSM). The optimal chromatographic conditions were achieved on a Zorbax C(18) column by gradient elution with 0.1% (v/v) aqueous formic acid and acetonitrile as mobile phase at the flow rate of 1.0 mL/min. The detection wavelength at 281 nm was chosen to determine the 15 bioactive components, namely danshensu (1), protocatechuic acid (2), protocatechuic aldehyde (3), caffeic acid (4), rosmarinic acid (5), lithospermic acid (6), salvianolic acid B (7), salvianolic acid A (8), salvianolic acid C (9); dihydrotanshinone I (10), cryptotanshinone (11), tanshinone I (12), methylene tanshiqunone (13), tanshinone IIA (14) and miltirone (15). Additionally, LC-ESI-TOF/MS was used to make definite identification of the constituents in samples in comparison with those reference compounds. The validation of the method included tests of linearity, sensitivity, repeatability, stability and recovery. The proposed method was successfully applied to quantify the 15 components in 21 samples; significant variations were demonstrated in the contents of the samples from diverse species and origins. The developed method could be used to effectively and comprehensively evaluate the quality of RRSM for its clinical safety and efficacy. PMID- 17853390 TI - Comparative modeling of marsupial MHC class I molecules identifies structural polymorphisms affecting functional motifs. AB - Major histocompatibility complex (MHC) class I molecules are transmembrane glycoproteins that present antigenic peptides to CD8+ T cells and are subsequently important for the initiation of an immune response. In this study novel MHC class I sequences from the tammar wallaby (Macropus eugenii) have been characterized. Analysis and comparative modeling of these and existing marsupial molecules reveals potential functional polymorphisms within peptide-binding grooves, MHC assembly motifs and the T cell receptor recognition interface. In addition, we show that a previously identified marsupial-specific insertion is within a region, which is known as a putative NK cell receptor (Ly49A) binding site in the mouse, suggesting that this site may be functionally active in marsupials. Further, the analysis highlighted differences in structural and sequence based grouping of marsupial MHC class I molecules. PMID- 17853391 TI - Executive function and genetic predisposition to schizophrenia--the Maudsley family study. AB - Executive cognitive impairment has been found in families affected by schizophrenia and is a putative endophenotype. We wished to explore its genetic basis further by studying the association between impairment and genetic loading for schizophrenia. We studied 30 schizophrenia patients with a family history of schizophrenia, 53 of their nonpsychotic first-degree relatives (familial), 32 patients with schizophrenia but no known family history of psychosis, 52 of their first-degree relatives (nonfamilial), and 47 normal controls. They were tested using the National Adult Reading Test (NART), Trails A and B, Verbal fluency tasks, and a computerized version of the Wisconsin Card Sorting Test (WCST). Familial, but not nonfamilial, relatives were impaired on NART, letter fluency, Trails B, and WCST total errors. They were inferior to nonfamilial relatives on letter fluency and Trails A. Both sets of relatives were impaired on Trails B controlling for Trails A, and on WCST categories achieved. There were no significant differences between schizophrenia patients with and without a family history. Our results suggest that executive deficits qualitatively similar to those seen in those with schizophrenia reflect familial susceptibility, even taking early IQ and education into consideration, consistent with a genetic mechanism. PMID- 17853392 TI - Race, biochemical disease recurrence, and prostate-specific antigen doubling time in the SEARCH database. PMID- 17853393 TI - Severe enteropathy among patients with stage II/III colon cancer treated on a randomized trial of bolus 5-fluorouracil/leucovorin plus or minus oxaliplatin: a prospective analysis. AB - BACKGROUND: Cases of severe gastrointestinal toxicity were monitored prospectively during NSABP C-07, a randomized clinical trial of adjuvant therapy for patients with stage II/III colon cancer. METHODS: Patients were treated with weekly bolus 5-fluorouracil (5-FU) and leucovorin (FL; "Roswell Park Regimen") or the same regimen plus oxaliplatin (FLOX). RESULTS: Of 1857 patients, 79 (4.3%) developed a syndrome of bowel wall injury (BWI, small or large) characterized by hospitalization for the management of severe diarrhea or dehydration and radiographic or endoscopic evidence of bowel wall thickening or ulceration. Fifty one (64.6%) of these adverse events occurred in patients treated with FLOX and 28 (35.4%) in those treated with FL (P < .01). Enteric sepsis (ES), characterized by grade 3 or greater diarrhea and grade 4 neutropenia with or without proven bacteremia occurred in 22 patients treated with FLOX, versus 8 in those treated with FL (P = .01). Patients >60 years were at higher risk for BWI after treatment with FLOX (6.7%) versus treatment with FL (2.9%, P < .01). Female patients had a higher incidence of BWI with FLOX (9.1%) than with FL (3.9%, P < .01). Severe gastrointestinal toxicity usually occurred during the third or fourth week on the first cycle of therapy, required hospitalization, and was managed with fluids, antidiarrheals, and antibiotics. There were 5 deaths (0.3%) due to enteropathy, 2 related to ES and 3 related to both BWI and ES. Seventy-one percent of patients resumed treatment with FL after recovery. CONCLUSIONS: Patients treated with adjuvant FL should be closely monitored for diarrhea and aggressively managed, especially if oxaliplatin has been added to the regimen. Society. PMID- 17853394 TI - Development of a model with which to predict the life expectancy of patients with spinal epidural metastasis. AB - BACKGROUND: The surgical treatment of spinal epidural metastasis is evolving. To be a surgical candidate, a patient should have a life expectancy of at least 3 months. Estimation of survival by experienced specialists has proven to be unreliable. METHODS: The Cox proportional hazards model was used to make a prediction model. To validate the model, Efron optimism correction by bootstrapping was performed. Retrospective data of patients treated for a spinal metastasis were used. Possible predictive factors were defined based on clinical experience and the literature. Statistical methods and clinical knowledge were also used to reveal an optimal set of predictors of survival. Data from patients treated at the Department of Radiation Oncology for spinal metastasis between 1998 and 2005 were evaluated. RESULTS: The case notes of 219 patients form the base of this study. In the final model, only 5 variables were required to predict the survival of a patient with spinal metastasis: sex, location of the primary lesion, intentional curative treatment of the primary tumor, cervical location of the spinal metastasis, and Karnofsky performance score. Examples with different predictors are given. The R(2) (N) index of Nagelkerke was 0.36 (95% confidence interval [95% CI], 0.28-0.48) and the c-index 0.72 (95% CI, 0.68-0.77). CONCLUSIONS: A reliable and simple model with which to predict the survival of a patient with spinal epidural metastasis is presented. Without the need for extensive investigations, survival can be predicted and only 5 easily obtainable parameters are required. PMID- 17853396 TI - Observation and characterization of a specific vibrational circular dichroism band in phenyl glycosides. AB - Application of vibrational circular dichroism (VCD) spectroscopy to structural analysis of carbohydrates has recently progressed. However, few studies on glycoconjugates VCD have thus far been reported, despite the fact that naturally occurring carbohydrates exist as various glycoconjugates. To further explore the application of the VCD technique, we have measured a series of aromatic glycosides and found that axial aromatic glycosides exhibited a negative band at around 1230 cm(-1) while equatorial ones showed flat features in this region. This is the first structure-spectra relationship on glycoconjugate VCD that distinguishes the stereochemistry of the sugar anomers. Several model compounds were prepared and their vibrational properties calculated by using the density functional theory (DFT) method, which assigned the vibrational mode of this band based on the stretching motion of the glycosidic oxygen and aromatic carbon. This concept that aglycan parts can reflect stereochemical information of sugar moieties may encourage further VCD studies on glycoconjugates to realize practical structural analysis of carbohydrates. PMID- 17853395 TI - Efficacy of gabapentin in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled, crossover trial (N00C3). AB - BACKGROUND: The antiepileptic agent, gabapentin, has been demonstrated to relieve symptoms of peripheral neuropathy due to various etiologies. On the basis of these data, a multicenter, double-blind, placebo-controlled, crossover, randomized trial was conducted to evaluate the effect of gabapentin on symptoms of chemotherapy-induced peripheral neuropathy (CIPN). METHODS: Patients with symptomatic CIPN who complained of 'average' daily pain scores of either 1) >/=4 on a 0-10 numerical rating scale (NRS); or 2) >/=1 on the 0-3 Eastern Cooperative Oncology Group neuropathy scale (ENS) were eligible (higher numbers indicate greater severity of symptoms in both scales). Patients were randomized to receive gabapentin (target dose, 2700 mg) or placebo for 6 weeks. Crossover occurred after a 2-week washout period. CIPN-related symptoms were evaluated weekly by questionnaires. Statistical methods followed established methods for crossover designs, including Student t tests to compare average intrapatient differences between treatments and linear models to adjust for potential concomitant covariates. RESULTS: There were 115 patients who were randomly assigned to the treatment or control arm. Both groups were well matched by symptoms at study entry. Changes in symptom severity were statistically similar between the 2 groups during the study. Adverse events were mild and similar in both groups. CONCLUSIONS: This trial failed to demonstrate any benefit to using gabapentin to treat symptoms caused by CIPN. PMID- 17853397 TI - An improved synthesis of 10,11-didehydro Cinchona alkaloids. AB - A revised procedure for the conversion of the four major Cinchona alkaloids (quinine, quinidine, cinchonidine, and cinchonine) into their respective 10,11 didehydro derivatives is described. The reported protocol offers several advantages over a recently published synthetic route. These include (i) enhanced robustness (ii) ready scalability (iii) reduced operational complexity and number of steps (iv) chromatography-free work-up. In addition, toxic solvents were replaced by environmentally less problematic alternatives. PMID- 17853398 TI - Measured and calculated CD spectra of G-quartets stacked with the same or opposite polarities. AB - Circular dichroism (CD) spectroscopy is widely used to characterize the structures of DNA G-quadruplexes. CD bands at 200-300 nm have been empirically related to G-quadruplexes having parallel or antiparallel sugar-phosphate backbones. We propose that a more fundamental interpretation of the origin of the CD bands is in the stacking interactions of neighboring G-quartets, which can have the same or opposing polarities of hydrogen bond acceptors and donors. From an empirical summation of CD spectra of the d(G)5 G-quadruplex and of the thrombin binding aptamer that have neighboring G-quartets with the same and opposite polarities, respectively, the spectra of aptamers selected by the Ff gene 5 protein (g5p) appear to arise from a combination of the two types of polarities of neighboring G-quartets. The aptamer CD spectra resemble the spectrum of d(G3T4G3), in which two adjacent quartets have the same and two have opposite polarities. Quantum-chemical spectral calculations were performed using a matrix method, based on guanine chromophores oriented as in d(G3T4G3). The calculations show that the two types of G-quartet stacks have CD spectra with features resembling experimental spectra of the corresponding types of G quadruplexes. PMID- 17853399 TI - Determination of the absolute configurations of natural products via density functional theory calculations of vibrational circular dichroism, electronic circular dichroism, and optical rotation: the iso-schizozygane alkaloids isoschizogaline and isoschizogamine. AB - The development of density functional theory (DFT) methods for the calculation of vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and transparent spectral region optical rotation (OR) has revolutionized the determination of the absolute configurations (ACs) of chiral molecules using these chiroptical properties. We report the concerted application of DFT calculations of VCD, ECD, and OR to the determination of the ACs of the isoschizozygane alkaloid natural products, isoschizogaline, and isochizogamine, whose ACs have not previously been determined. The ACs of naturally occurring (-) isoschizogaline and (-)-isoschizogamine, are both determined definitively to be 2R, 7R, 20S, 21S. PMID- 17853400 TI - Dopamine beta-hydroxylase (DBH) activity and -1021C/T polymorphism of DBH gene in combat-related post-traumatic stress disorder. AB - The roles of dopamine (DA) and norepinephrine (NE) in posttraumatic stress disorder (PTSD) are unclear. The aim of the study was to determine plasma dopamine beta-hydroxylase (DBH) activity and DBH-1021C/T gene polymorphism in combat veterans with (N = 133) or without (N = 34) chronic PTSD. Similar frequencies in genotype or allele distribution were found between veterans with or without PTSD. War veterans with PTSD had lower DBH activity, associated with the DBH-1021C/T variant in DBH genes, than veterans without PTSD. A significantly lower plasma DBH activity was found in combat veterans with PTSD carrying the CC genotype as compared to veterans without PTSD carrying the corresponding genotype. Since both groups were exposed to the same trauma, it is possible that a pre-existing trait difference in regulation of NE function contributed to a differential vulnerability to develop PTSD, or that the regulation of DBH expression was different in response to trauma. The results suggest that that genotype-controlled measurement of plasma DBH activity might be used as a potential biological marker of the response to trauma, and that further studies of DBH and other loci related to DA and NA in PTSD are warranted. PMID- 17853401 TI - Spider capture silk: performance implications of variation in an exceptional biomaterial. AB - Spiders and their silk are an excellent system for connecting the properties of biological materials to organismal ecology. Orb-weaving spiders spin sticky capture threads that are moderately strong but exceptionally extensible, resulting in fibers that can absorb remarkable amounts of energy. These tough fibers are thought to be adapted for arresting flying insects. Using tensile testing, we ask whether patterns can be discerned in the evolution of silk material properties and the ecological uses of spider capture fibers. Here, we present a large comparative data set that allows examination of capture silk properties across orb-weaving spider species. We find that material properties vary greatly across species. Notably, extensibility, strength, and toughness all vary approximately sixfold across species. These material differences, along with variation in fiber size, dictate that the mechanical performance of capture threads, the energy and force required to break fibers, varies by more than an order of magnitude across species. Furthermore, some material and mechanical properties are evolutionarily correlated. For example, species that spin small diameter fibers tend to have tougher silk, suggesting compensation to maintain breaking energy. There is also a negative correlation between strength and extensibility across species, indicating a potential evolutionary trade-off. The different properties of these capture silks should lead to differences in the performance of orb webs during prey capture and help to define feeding niches in spiders. PMID- 17853402 TI - Mortality and cancer incidence in a cohort of registered nurses from British Columbia, Canada. AB - BACKGROUND: A retrospective cohort study of provincial registered nurses (RNs) from British Columbia, Canada was undertaken to determine risks of mortality and cancer incidence; in particular for breast cancer and leukemia. METHODS: Cohort records of RNs from 1974 to 2000 were linked to Canadian death and cancer registries. Analyses included standardized mortality (SMR) and incidence ratios (SIR) as well as relative risks for internal comparisons. RESULTS: There were 58,125 RNs in the cohort (96.7% females). The SMR for all causes of mortality for female RNs was low, at 0.61 (95% CI, 0.58-0.64). The only elevated SIR for female RNs was for malignant melanoma (1.27; 95% CI, 1.10-1.46). Ever working in a hospital, medical surgical specialties or maternal/pediatrics showed some elevated cancer risks. CONCLUSIONS: Low SMRs for the female RN cohort suggest healthful lifestyles and a healthy worker effect. Length of employment as a nurse, in hospitals and in specific fields was associated with some increased risks of cancer. PMID- 17853403 TI - Mast cells appearing in long-term skeletal muscle cell cultures of rat. AB - Mast cells are known to be involved in type I allergy and to be localized in almost all tissues in the body. However, they have slightly different properties depending on their tissue of residence. Although mast cells are found in skeletal muscle tissue, there have been no reports of their appearance in cultured skeletal muscles. We report here that mast cells appear in long-term cultures of skeletal muscles from neonatal rats and rat fetuses. When muscle cells were disseminated and cultured in minimum essential medium with 10% fetal calf serum and 10% horse serum, oval cells containing large granules started to appear on myotube sheets at 5 days of culture. These oval cells continued to proliferate for 2-3 months, and showed immunoreactivity for histamine, tryptase, Fc(epsilon)RI, and c-kit. They showed metachromatic staining with 0.5% toluidine blue at pH 0.5 and were stained with both Alcian blue and safranin. Biochemically measured histamine content per dish was significantly higher in 2-month than in 5 day culture. From these results, we concluded that these oval cells were mast cells. Because proteases from mast cells have been reported previously to affect myoblast proliferation, the present findings suggest that there may be some interaction between mast cells and muscle cell proliferation or differentiation. The present finding that mast cells are easily obtained from ordinary skeletal muscle cultures provides a useful method for the study of the diverse functions of mast cells. PMID- 17853404 TI - Genetics of tension-type headache: a population based twin study. AB - The purpose was to investigate the importance of genetic and environmental factors in tension-type headache using a genetic modeling analysis. Twins age 12 41 years old from the population based Danish Twin Registry received a validated posted questionnaire about tension-type headache and migraine. Inclusion required that both twins in a pairs replied on the questionnaire and known zygosity. Twin pairs where one or both twins had co-occurrence of migraine were excluded. Migraine significantly increases the risk as well as the frequency of tension type headache. The quantitative genetic modeling included 2,437 monozygotic (MZ), 2,720 same gender dizygotic (DZ), and 2,203 opposite gender DZ twin pairs without co-occurrence of migraine. Polychoric correlations were significantly higher in MZ than same gender DZ twin pairs analyzed separately by gender, while polychoric correlation were higher in same gender than opposite gender DZ twin pairs, although this was not significant in the comparison with male same gender DZ twin pairs. The best fitting model is based on gender specific prevalence and variance components without gender specific genetic effects. Heritability estimates of 48% in men and 44% in women were obtained. Genetic effects contribute to nearly half of variance in the liability to tension-type headache. PMID- 17853405 TI - Epithelial and muscular regionalization of the human developing anorectum. AB - In the past, interpretations of anorectal development were mainly based on analysis of serially sectioned embryos of various nonhuman species as well as some human specimens. A four-dimensional view of the developmental situation in the human has never been established nor connected to recent findings obtained from newer molecular techniques. We, therefore, investigated human embryonic and fetal pelves by means of immunohistochemistry and in situ hybridization to elucidate differentiation and interaction of epithelial and mesenchymal layers of the anorectum. To emphasize spatial as well as sequential morphological development, we produced three-dimensional reconstructions of the specimens at hand. Research conducted proved that the decisive steps of epithelial and muscular differentiation occur between the 7th and 9th week after conception. This study elucidates a biphasic epithelial "closure" in the anal canal and interactions between epithelium, smooth musculature, and skeletal musculature. Based on the results presented here, it is possible to describe the pathogenesis of two anorectal malformations: the imperforate anal membrane and the anal membrane stenosis. This study will now provide the basis for further research into developmental processes occurring before the ones examined. PMID- 17853406 TI - Statistical methods for anomalous discrete time series based on minimum cell count. AB - Temporal incidence patterns of point epidemics often contain periods of unusually low or high frequencies. Identifying variations in incidence frequencies, which may be caused by changes in exposure to infectious or environmental agents, may provide important insights into the pathogenesis or etiology of a disease. We propose and formulate new statistical tests for temporal and space-time anomalies that are based on the minimum frequency in a unit of time and that are meaningful for the characteristic incidence patterns of the cases studied. Among the most widely applied methods are the Ederer-Myers-Mantel test, the Maxima test, and the scan test, which are all sensitive to the maximum frequency within a short period of time. We elucidate the importance and utility of our new tests and the existing tests and suggest a systematic statistical analysis of reported disease anomalies using these tests combined. Data on a temporal series of adolescent suicide from the US National Center for Health Statistics were analyzed using these methods. PMID- 17853407 TI - TLR agonists induce the differentiation of human bone marrow CD34+ progenitors into CD11c+ CD80/86+ DC capable of inducing a Th1-type response. AB - We recently reported that human bone marrow hematopoietic CD34(+) progenitors express functional Toll-like receptors (TLR) and can differentiate into myeloid cells just by stimulation with resiquimod (R848), a specific agonist for TLR7/8. However, the mechanisms by which R848 induces cell differentiation, the effects of other TLR agonists and the functionality of the differentiated cells are not known. Comparable to R848, loxoribine (a TLR7 agonist) and Pam(3)CSK(4) (a TLR2 agonist) induced cytokine production and cell differentiation along the myeloid lineage. R848 and loxoribine were more effective than Pam(3)CSK(4) at inducing the lineage-negative (CD11c(+) CD14(-)) dendritic cells (DC), whereas Pam(3)CSK(4) was more effective at inducing CD11c(+) CD14(+) monocytes. Both cell subsets expressed CD80/CD86 and HLA-DR molecules; however, they showed differential expression of CD1a, CD1b, CD1c, CD11b, CD206 and CD207 markers when compared with each other. Cell differentiation into DC was significantly inhibited by an anti-TNF-alpha nonoclonal antibody. The CD11c(+) CD14(-) subset was isolated and shown to be more potent in stimulating an alloreaction than the CD11c(+) CD14(+) subset. Collectively, these data highlight the differential effects of TLR agonists on human bone marow CD34(+) progenitor cells and provide a new opportunity for generating functional DC that would be useful in cancer vaccination. PMID- 17853408 TI - Up-regulation of leukocyte CXCR4 expression by sulfatide: an L-selectin-dependent pathway on CD4+ T cells. AB - CXCR4 plays significant roles in immune and inflammatory responses and is important for selective recruitment of leukocytes. We previously showed that CXCR4 surface expression of human lymphocytes was affected by sulfatide, an in vivo ligand for L-selectin. Increased CXCR4 expression was shown to promote biologically relevant functions such as integrin-dependent adhesion and transmigration. Here, we show that sulfatide-induced CXCR4 up-regulation also occurs on other leukocyte subsets in humans and mice. B cells and CD4(+)CD25(+) T cells had the highest CXCR4 up-regulation after sulfatide stimulation. Transfection of L-selectin was sufficient for K562 cells to acquire sulfatide induced CXCR4 up-regulation, while analysis of L-selectin knockout mice revealed that this response was critically L-selectin dependent only for CD4(+) T cells, suggesting an alternative pathway in CD8(+) T cells and B cells. Sulfatide triggered several intracellular signaling events in CD4(+) T cells, but only tyrosine kinase activation, including members of the Src family, were essential for L-selectin to CXCR4 signaling. CXCR4 up-regulation was rapid, enhanced CXCL12 induced signaling and increased chemotaxis toward CXCL12, and therefore has potentially important roles in vivo. Thus, the response to CXCL12 depends in part on tissue expression of sulfatide and, specifically in CD4(+) T cells, also depends on the surface level of L-selectin. PMID- 17853409 TI - MyD88-dependent autoimmune disease in Lyn-deficient mice. AB - Recent evidence suggests that systemic autoimmune disease depends on signals from TLR ligands, but little is known about how TLR-dependent pathways lead to the loss of self tolerance in vivo. To address this, we have examined the role of TLR signaling in Lyn-deficient mice, which develop an autoimmune disease similar to SLE. We found that absence of the TLR signaling adaptor molecule MyD88 suppresses plasma cell differentiation of switched and unswitched B cells, and prevents the generation of antinuclear IgG antibodies and glomerulonephritis. In mixed chimeras the increased IgM and IgG antibody secretion in Lyn-deficient mice is at least partially due to B cell-independent effects of Lyn. We now show that MyD88 deficiency blocks the expansion and activation of DC in which Lyn is also normally expressed, and prevents the hypersecretion of proinflammatory cytokines IL-6 and IL-12 by Lyn-deficient DC. These findings further highlight the important role of TLR-dependent signals in both lymphocyte activation and autoimmune pathogenesis. PMID- 17853410 TI - IL-33 is a chemoattractant for human Th2 cells. AB - IL-33 is a novel cytokine of the IL-1 family and mediates its biological effect via the receptor ST2, which is selectively expressed on Th2 cells but not Th1 cells. IL-33 drives production of Th2-associated cytokines including IL-5 and IL 13 and thereby promotes defense and pathology in mucosal organs. Cell locomotion is crucial to the induction of an effective immune response. We report here the chemoattraction of Th2 cells by IL-33. Recombinant IL-33 increased the proportion of human Th2 cells, but not Th1 cells, in polarized morphology in vitro and stimulated their subsequent invasion into collagen gels in an IL-33 concentration dependent manner. Injection of recombinant IL-33 into the footpad of ST2(-/-) mice which had been adoptively transferred with polarized Th2 cells, led to local accumulation of the transferred Th2 cells. These data therefore demonstrate that IL-33 is a selective Th2 chemoattractant associated with the pro-inflammatory property of this novel cytokine. PMID- 17853411 TI - TLR9 activation is a key event for the maintenance of a mycobacterial antigen elicited pulmonary granulomatous response. AB - Type 1 (Th1) granulomas can be studied in mice sensitized with mycobacterium antigens followed by challenge of agarose beads covalently coupled to purified protein derivative. TLR9 is known to play a role in the regulation of Th1 responses; thus, we investigated the role of TLR9 in granuloma formation during challenge with mycobacterium antigens and demonstrated that mice deficient in TLR9 had increased granuloma formation, but a dramatically altered cytokine phenotype. Th1 cytokine levels of IFN-gamma and IL-12 in the lungs were decreased in TLR9(-/-) mice when compared to wild-type mice. In contrast, Th2 cytokine levels of IL-4, IL-5, and IL-13 were increased in TLR9(-/-) mice. The migration of CD4(+) T cells in the granuloma was impaired, while the number of F4/80(+) macrophages was increased in TLR9(-/-) mice. Macrophages in the lungs of the TLR9 deficient animals with developing granulomas expressed significantly lower levels of the classically activated macrophage marker, nitric oxide synthase, but higher levels of the alternatively activated macrophage markers such as 'found in inflammatory zone-1' antigen and Arginase-1. These results suggest that TLR9 plays an important role in maintaining the appropriate phenotype in a Th1 granulomatous response. PMID- 17853412 TI - Inhibition of mRNA synthesis in the hippocampus impairs consolidation and reconsolidation of spatial memory. AB - Using two different mRNA synthesis inhibitors, we show that blockade of hippocampal gene expression during restricted posttraining or postretrieval time windows hinders retention of long-term spatial memory for the Morris water maze task, without affecting short-term memory, nonspatial learning, or the functionality of the hippocampus. Our results indicate that spatial memory consolidation induces the activation of the hippocampal transcriptional machinery and suggest the existence of a gene expression-dependent reconsolidation process that operates in the dorsal hippocampus at the moment of retrieval to stabilize the reactivated mnemonic trace. PMID- 17853413 TI - Memory for familiar environments learned in the remote past: fMRI studies of healthy people and an amnesic person with extensive bilateral hippocampal lesions. AB - Preserved remote spatial memory in amnesic people with bilateral hippocampal damage, including the well-studied case K.C., challenges spatial theories, which assume that the hippocampus is needed to support all allocentric spatial representations, old or new. It remains possible, however, that residual hippocampal tissue is functional and contributes to successful performance. Here, we examine brain activity with fMRI during the retrieval of spatial information in K.C. and in healthy controls using landmark and route stimuli from a premorbidly familiar neighborhood that K.C. can navigate normally. In all participants, activity was found in the parahippocampal cortex, but not in the hippocampus itself, during all navigational tasks on which K.C. performs well, even though part of his hippocampus remains viable. The opposite pattern was observed on a house recognition task, which is inconsequential to navigation, and on which K.C. performed poorly. On that task, K.C. recruited the right hippocampus presumably because even "familiar" houses were treated as novel by him, whereas controls recruited occipitotemporal cortex, including parahippocampal cortex. The distinction between recent and remote memory, therefore, may apply as much to spatial theories of hippocampal function as it does to theories emphasizing the role of the hippocampus in other types of explicit memory. PMID- 17853414 TI - Large image microscope array for the compilation of multimodality whole organ image databases. AB - Three-dimensional, structural and functional digital image databases have many applications in education, research, and clinical medicine. However, to date, apart from cryosectioning, there have been no reliable means to obtain whole organ, spatially conserving histology. Our aim was to generate a system capable of acquiring high-resolution images, featuring microscopic detail that could still be spatially correlated to the whole organ. To fulfill these objectives required the construction of a system physically capable of creating very fine whole-organ sections and collecting high-magnification and resolution digital images. We therefore designed a large image microscope array (LIMA) to serially section and image entire unembedded organs while maintaining the structural integrity of the tissue. The LIMA consists of several integrated components: a novel large-blade vibrating microtome, a 1.3 megapixel peltier cooled charge coupled device camera, a high-magnification microscope, and a three axis gantry above the microtome. A custom control program was developed to automate the entire sectioning and automated raster-scan imaging sequence. The system is capable of sectioning unembedded soft tissue down to a thickness of 40 microm at specimen dimensions of 200 x 300 mm to a total depth of 350 mm. The LIMA system has been tested on fixed lung from sheep and mice, resulting in large high quality image data sets, with minimal distinguishable disturbance in the delicate alveolar structures. PMID- 17853415 TI - Claudin-7 expressed on lateral membrane of rat epididymal epithelium does not form aberrant tight junction strands. AB - Claudins are integral membrane proteins at tight junctions (TJs) and form TJ strands. In the present study, we found that claudin-7 was localized along the entire lateral membranes of epididymal epithelium, including the apical junctional region throughout the epididymis, but claudin-8 was restricted to the apical junctional region. This finding raises the possibility that aberrant TJ strands may be formed on lateral membranes. Thus, we focused on examining whether TJ strands exist on lateral membranes of epididymal epithelium. Freeze-fracture electron microscopy showed that aberrant TJ strands were observed in only a few principal cells in all segments of the epididymis except for the initial segment, indicating that the occurrence of aberrant strands is very rare. Aberrant TJ strands were smooth and not subdivided into individual particles in the protoplasmic face, and complementary grooves in the extracellular face were almost free of particles. Aberrant TJ strands in the distal caput and corpus epididymis were accompanied by many vesicle-like structures but those in the proximal caput and cauda epididymis were not. These results suggest that most of claudin-7 in lateral membranes may exist in a nonpolymerized form and may play some different roles other than the formation of TJ strands, for example, in the formation of a pool of claudin proteins or in the reinforcement of cell adhesion. PMID- 17853416 TI - Preliminary tribological evaluation of nanostructured diamond coatings against ultra-high molecular weight polyethylene. AB - BACKGROUND: Some loss of joint prostheses has been attributed to osteolytic loosening associated with debris from wear of polyethylene articulating against metal alloys. Reduced polyethylene wear has been reported with ceramics serving as an alternative counterface. METHODS: Nanostructured Diamond (NSD) coatings were deposited onto Ti6Al4V by microwave plasma-assisted chemical vapor deposition, with both hydrogen-rich (H-NSD) and helium-rich (He-NSD) feedgas mixtures. Pin-on-disk wear tests of polyethylene against NSD and CoCr were performed in serum lubrication at body temperature. Scanning electron microscopy was used to examine surface morphology, and nanoindentation was used to determine hardness and modulus of the polyethylene wear surfaces. Raman spectroscopy, surface roughness, and wettability analyses of the NSD coatings were performed. RESULTS: Raman spectroscopy confirmed sp(2) and sp(3) bonded carbon in the NSD coatings. No significant differences in wear factors were found between polyethylene on H-NSD, He-NSD, and CoCr, despite higher roughness and friction coefficients for the He-NSD and H-NSD coatings, compared with CoCr. Contact angles for the diamond coatings were reduced following the wear tests, indicating that these surfaces became more hydrophilic. Numerous small protuberances were observed on pins articulated against CoCr, and a single, large protuberance was observed in polyethylene-on-NSD. These features were conjectured to be reconsolidated polyethylene particles. Nanoindentation modulus and hardness of the worn polyethylene surfaces were lower for polyethylene-on-diamond than for polyethylene-on-CoCr. CONCLUSIONS: As a counterface to polyethylene, NSD-coated Ti6Al4V produced wear factors comparable to CoCr in the present pin-on-disk tests, a promising step towards its use in joint replacement bearing applications. PMID- 17853417 TI - An examination of fatigue striations in human dentin: in vitro and in vivo. AB - Although striations are often used in evaluating fatigue crack growth in engineering materials, they have not been used in studying the mechanics of fracture in hard tissues. The primary objective of this study was to evaluate the striations resulting from fatigue crack growth in the dentin of human teeth. Compact tension (CT) specimens obtained from the coronal dentin of molars from young (17 < or = age < or = 37 years) and senior (age > or = 50 years) patients were subjected to cyclic Mode I loads. Striations evident on the fracture surfaces were examined using a scanning electron microscope (SEM) and contact profilometer. Fatigue crack growth striations that developed in vivo were also examined on fracture surfaces of restored molars. A power spectrum analysis of surface profiles from the CT specimens showed that the striation spacing ranged from 50 to 170 microm. The average spacing in the dentin of seniors (130 +/- 23 microm) was significantly larger (p < 0.001) than that in young dentin (88 +/- 13 microm). Fatigue striations in the restored teeth exhibited features that were consistent with those that developed in vitro and a spacing ranging from 59 to 95 microm. Unlike metals, the striations in dentin developed after a period of cyclic loading that ranged from 1 x 10(3) to 1 x 10(5) cycles. A quantitative evaluation of the striation spacing using the Bates-Clark equation suggested that cyclic crack growth within the restored teeth occurred at a stress intensity range near 0.7 MPa x m(0.5), and a stress range of approximately 12 MPa. PMID- 17853418 TI - Effects of irradiance, wavelength, and thermal emission of different light curing units on the Knoop and Vickers hardness of a composite resin. AB - The aim of this study was to evaluate the effects of irradiance, light emission wavelength, and heating of different light curing units on the Knoop and Vickers hardness of a hybrid composite resin. The specimens were irradiated during 40 s with ten different light curing units, LEDs, and halogen lights. The spectral emission of each light curing unit was assessed by a spectrometer, the irradiance was measured by two commercial radiometers, and the heating measured with a thermocouple. After 48 h of storage in a dark recipient under a 100% humidity condition, the Knoop and Vickers hardness tests were carried out. The hardness results were analyzed by ANOVA, and Tukey HSD test (p < 0.05). The results showed that the surface hardness of the composite resin depends not only on the irradiance, but strongly on the emission wavelength and heating of the light curing units. It was observed, a linear correlation between the conversion degree and radiant exposure. In addition, it is suggested that the well known base to top surface hardness ratio convention of 80-90% is not appropriate to evaluate curing efficiency of composites, since the top surface is not always sufficiently polymerized. PMID- 17853419 TI - The human micro-vascular endothelial cells in vitro interaction with atomic nitrogen-doped diamond-like carbon thin films. AB - This paper reports the initial response of atomic nitrogen doped diamond like carbon (DLC) to endothelial cells in vitro. The introduction of nitrogen atoms/molecules to the diamond like carbon structures leads to an atomic structural change favorable to the attachment of human micro-vascular endothelial cells. Whilst the semi-conductivity induced by nitrogen in DLC is thought to play a part, the increase in the non-bonded N atoms and N(2) molecules in the atomic doped species (with the exclusion of the charged species) seems to contribute to the improved attachment of human microvascular endothelial cells. The increased endothelial attachment is associated with a lower work function and slightly higher water contact angle in the atomic doped films, where the heavy charged particles are excluded. The films used in the study were synthesized by the RF PECVD technique followed by post deposition doping with nitrogen, and afterwards the films were characterized by XPS, Raman spectroscopy, SIMS and Kelvin probe. The water contact angles were measured, and the counts of the adherent endothelial cells on the samples were carried out. This study is relevant and contributory to improving biocompatibility of surgical implants and prostheses. PMID- 17853420 TI - Comparison of the release behaviors of cupric ions from metallic copper and a novel composite in simulated body fluid. AB - The copper-containing intrauterine devices (Cu-IUDs) are being increasingly used worldwide as an effective contraceptive for family planning. To avoid abnormal bleeding, pain, and partial and complete expulsion which are associated with the burst release of copper during the first few days, a novel crosslinked composite based on poly(vinyl alcohol) that contained cupric ions, but not metallic copper, was synthesized. It is hypothesized that the burst release of cupric ions could be avoided and the utility of the cupric ions could be improved by this novel composite. To evaluate these effects of the composite, the corrosion products and the release rate of cupric ions after soaking in simulated body fluid (SBF) for different time spans were studied by environmental scanning electron microscopy, X-ray energy dispersive spectroscopy, X-ray diffraction, and atomic absorption spectrophotometer. In the first week, the release amount of cupric ions in the composite was 0.486 microg/mm(2). In the fifth week, it decreased to 0.0278 microg/mm(2). But for metallic copper, these were 5.93 microg/mm(2) and 0.041 microg/mm(2), respectively. No significant change on time-dependence was found for the release rates of cupric ions in the composite compared with that of metallic copper. Moreover, no other new elements, such as P, Cl, and Ca, appeared on the surface of the composite, and no Cu2O was formed after immersing in SBF for 90 days. All of these results suggested that burst release of cupric ions could be avoided and the effective utility of copper could be improved in this composite. In view of the earlier results, this novel copper-containing composite might serve as a potential substitute for conventional materials of IUDs in the future. PMID- 17853421 TI - Calcium phosphate-based coatings on titanium and its alloys. AB - Use of titanium as biomaterial is possible because of its very favorable biocompatibility with living tissue. Titanium implants having calcium phosphate coatings on their surface show good fixation to the bone. This review covers briefly the requirements of typical biomaterials and narrowly focuses on the works on titanium. Calcium phosphate ceramics for use in implants are introduced and various methods of producing calcium phosphate coating on titanium substrates are elaborated. Advantages and disadvantages of each type of coating from the view point of process simplicity, cost-effectiveness, stability of the coatings, coating integration with the bone, cell behavior, and so forth are highlighted. Taking into account all these factors, the efficient method(s) of producing these coatings are indicated finally. PMID- 17853422 TI - Human tooth culture: a study model for reparative dentinogenesis and direct pulp capping materials biocompatibility. AB - In a previous work, based on an in vitro entire tooth culture model of human immature third molars, we demonstrated that perivascular progenitor cells can proliferate and migrate to the injury site after pulp exposure. In this work, we investigated the differentiation of cells after direct capping with biomaterials classically used in restorative dentistry. Histological staining after direct pulp capping with Calcium Hydroxide XR(R) or MTA revealed early and progressive mineralized foci formation containing BrdU-labeled sequestered cells. The molecular characterization of the matrix and the sequestered cells by immunohistochemistry (Collagene type I, Dentin sialoprotein, and Nestin) clearly demonstrates that these areas share common characteristics of the mineralized matrix of reparative dentin formed by odontoblast-like cells. This reproduces some features of the pulp responses after applying these materials in vivo and demonstrates that the entire tooth culture model reproduces a part of the early steps of dentin regeneration in vivo. Its future development may be useful in studying the effects of biomaterials on this process. PMID- 17853423 TI - Development of acellular dermis from porcine skin using periodic pressurized technique. AB - In this work, a new method for producing acellular dermis (ADM), a natural scaffold used for dermal replacement, from porcine skin was developed. Fresh porcine skin from local slaughterhouse was dehaired by sodium sulphide following by epidermis removal using glycerol. After fat removal by chloroform/methanol (2/1 v/v) solvent, cellular components were removed using enzymatic treatment incorporated with a periodic pressurized technique. The effects of enzyme type (trypsin and dispase II) and periodic pressurized conditions on the efficiency of cell removal were investigated. When periodic pressure was applied, enzymatic treatment time could be shorten since the enzyme solution was able to penetrate into tight dermis. As a result, cells could be easily removed from porcine skin as noticed quantitatively by DNA assay and qualitatively by H&E staining. When enzyme refreshment was introduced into the decellularized process, the percentage of cell removal was further enhanced. This ensured that no inhibitions effect from the removed cells on enzyme-substrate interaction. Moreover, short-time enzymatic treatment with periodic pressurized technique could prevent the disruption of dermal structure, as observed by SEM. Dispase II can be used to remove cell better than trypsin in the periodic pressurized technique. However, in vivo study indicated that numerous fibroblast from the host tissue infiltrated into ADM prepared using both enzymes. Neo-collagen and neo-capillaries were produced in both implanted ADMs. The result elucidated that the use of periodic pressurized technique with enzymatic treatment has a high potential to be a new method to produce ADM for skin tissue engineering. PMID- 17853424 TI - Structural changes of UHMWPE after e-beam irradiation and thermal treatment. AB - Ultra-high molecular weight polyethylene (UHMWPE) was irradiated with accelerated electrons (1 MeV in air) using high dose rates (> 25 kGy/min) and thin specimens (thickness 1 mm). Parts of the specimens were remelted (200 degrees C for 10 min; 150 degrees C for 0, 2, 10, 30, 60 min). All specimens were stored in nitrogen in the dark at 5 degrees C. Supermolecular structure, extent of crosslinking, oxidative degradation, and macroradical content were studied by a number of methods (SAXS, WAXS, SEM, DSC, FTIR, ESR, TGA, solubility experiments, image analysis). The results obtained with irradiated samples were compared with those obtained with irradiated and remelted samples. It was confirmed that crosslinking predominates over chain scission at very high dose rates, even if the irradiation is performed in air. Discrepancies concerning supermolecular structure changes in UHMWPE after irradiation and thermal treatment, found in various studies in the literature, are discussed. A simple model, which describes and explains all supermolecular structure changes, is introduced. An effective way of eliminating residual macroradicals in UHMWPE is proposed. PMID- 17853425 TI - The impact of missing data and how it is handled on the rate of false-positive results in drug development. AB - In drug development, a common choice for the primary analysis is to assess mean changes via analysis of (co)variance with missing data imputed by carrying the last or baseline observations forward (LOCF, BOCF). These approaches assume that data are missing completely at random (MCAR). Multiple imputation (MI) and likelihood-based repeated measures (MMRM) are less restrictive as they assume data are missing at random (MAR). Nevertheless, LOCF and BOCF remain popular, perhaps because it is thought that the bias in these methods lead to protection against falsely concluding that a drug is more effective than the control. We conducted a simulation study that compared the rate of false positive results or regulatory risk error (RRE) from BOCF, LOCF, MI, and MMRM in 32 scenarios that were generated from a 2(5) full factorial arrangement with data missing due to a missing not at random (MNAR) mechanism. Both BOCF and LOCF inflated RRE were compared to MI and MMRM. In 12 of the 32 scenarios, BOCF yielded inflated RRE compared with eight scenarios for LOCF, three scenarios for MI and four scenarios for MMRM. In no situation did BOCF or LOCF provide adequate control of RRE when MI and MMRM did not. Both MI and MMRM are better choices than either BOCF or LOCF for the primary analysis. PMID- 17853426 TI - Synthesis and in vitro characterization of novel dextran-methylprednisolone conjugates with peptide linkers: effects of linker length on hydrolytic and enzymatic release of methylprednisolone and its peptidyl intermediates. AB - To control the rate of release of methylprednisolone (MP) in lysosomes, new dextran-MP conjugates with peptide linkers were synthesized and characterized. Methylprednisolone succinate (MPS) was attached to dextran 25 kDa using linkers with 1-5 Gly residues. The release characteristics of the conjugates in pH 4.0 and 7.4 buffers, blood, liver lysosomes, and various lysosomal proteinases were determined using a size-exclusion and/or a newly developed reversed-phase HPLC method capable of simultaneous quantitation of MP, MPS, and all five possible MPS peptidyl intermediates. We synthesized conjugates with >or=90% purity and 6.9 9.5% (w/w) degree of MP substitution. The conjugates were stable at pH 4.0, but released MP and intact MPS-peptidyl intermediates in the pH 7.4 buffer and rat blood, with faster degradation rates for longer linkers. Rat lysosomal fractions degraded the conjugates to MP and all the possible intermediates also at a rate directly proportional to the length of the peptide. Whereas the degradation of the conjugates by cysteine peptidases (papain or cathepsin B) was relatively substantial, no degradation was observed in the presence of aspartic (cathepsin D) or serine (trypsin) proteinases, which do not cleave peptide bonds with Gly. These newly developed dextran conjugates of MP show promise for controlled delivery of MP in lysosomes. PMID- 17853427 TI - Use of manometric temperature measurement (MTM) and SMART freeze dryer technology for development of an optimized freeze-drying cycle. AB - This report provides, for the first time, a summary of experiments using SMART Freeze Dryer technology during a 9 month testing period. A minimum ice sublimation area of about 300 cm(2) for the laboratory freeze dryer, with a chamber volume 107.5 L, was found consistent with data obtained during previous experiments with a smaller freeze dryer (52 L). Good reproducibility was found for cycle design with different type of excipients, formulations, and vials used. SMART primary drying end point estimates were accurate in the majority of the experiments, but showed an over prediction of primary cycle time when the product did not fully achieve steady state conditions before the first MTM measurement was performed. Product resistance data for 5% sucrose mixtures at varying fill depths were very reproducible. Product temperature determined by SMART was typically in good agreement with thermocouple data through about 50% of primary drying time, with significant deviations occurring near the end of primary drying, as expected, but showing a bias much earlier in primary drying for high solid content formulations (16.6% Pfizer product) and polyvinylpyrrolidone (40 kDa) likely due to water "re-adsorption" by the amorphous product during the MTM test. PMID- 17853428 TI - Using a modified shepards method for optimization of a nanoparticulate cyclosporine a formulation prepared by a static mixer technique. AB - An innovative methodology has been used for the formulation development of Cyclosporine A (CyA) nanoparticles. In the present study the static mixer technique, which is a novel method for producing nanoparticles, was employed. The formulation optimum was calculated by the modified Shepard's method (MSM), an advanced data analysis technique not adopted so far in pharmaceutical applications. Controlled precipitation was achieved injecting the organic CyA solution rapidly into an aqueous protective solution by means of a static mixer. Furthermore the computer based MSM was implemented for data analysis, visualization, and application development. For the optimization studies, the gelatin/lipoid S75 amounts and the organic/aqueous phase were selected as independent variables while the obtained particle size as a dependent variable. The optimum predicted formulation was characterized by cryo-TEM microscopy, particle size measurements, stability, and in vitro release. The produced nanoparticles contain drug in amorphous state and decreased amounts of stabilizing agents. The dissolution rate of the lyophilized powder was significantly enhanced in the first 2 h. MSM was proved capable to interpret in detail and to predict with high accuracy the optimum formulation. The mixer technique was proved capable to develop CyA nanoparticulate formulations. PMID- 17853429 TI - Species differences in in vitro and in vivo small intestinal metabolism of CYP3A substrates. AB - Intestinal first-pass metabolism has a great impact on the bioavailability of CYP3A substrates in humans, and the in vivo impact has quantitatively been evaluated using CYP3A inhibitors or inducers. In vitro and in vivo preclinical investigations for intestinal metabolism are essential in clarifying pharmacokinetic behavior in animal species and predicting the effect of intestinal metabolism in the human. In this review, we will discuss species differences in intestinal CYP3A enzymes, and CYP3A-mdediated intestinal elimination. Identical CYP3A4 enzyme is expressed in human intestine and liver, but different CYP3A enzymes in both tissues of the mouse and rat are found, that is, respective intestinal enzyme is considered as cyp3a13 and CYP3A62. There is little information on CYP3A enzymes in the monkey and dog intestine, unlike the liver. In vitro metabolic activities of midazolam and nisoldipine are higher in the human and monkey than in the rat. In vivo assessment of cyclosporine, midazolam, nifedipine, tacrolimus, and verapamil has been reported in various species (monkey, rat, mouse, and/or dog) including the human. For midazolam, the monkey shows significant in vivo intestinal metabolism, as evidenced in the human. The monkey might be an appropriate animal model for evaluating small intestinal first-pass metabolism of CYP3A substrates. PMID- 17853430 TI - Preparation and evaluation of poly-butylcyanoacrylate nanoparticles for oral delivery of thymopentin. AB - Thymopentin (Tp5) was loaded in poly-butylcyanoacrylate (PBCA) nanoparticles (NP) in order to enhance the oral bioavailability of Tp5. PBCA-Tp5-NP was prepared by nanoprecipitation methods. Dialyzing membrane method was employed to examine the in vitro release of PBCA-Tp5-NP in PBS, and Tp5 samples in the release medium were detected by HPLC. The cell proliferation test ((3)H-thymidine) was conducted to verify the PBCA-Tp5-NP bioactivity in vitro. The pharmacodynamical studies were performed on preimmunoinhibited rats and in flow cytometer. The size and the entrapment efficiency of PBCA-Tp5-NP were 178 +/- 39 nm and 92.21 +/- 1.08%, respectively. In vitro release data show that less than 60% Tp5 was released from lyophilized PBCA-Tp5-NP while 80% Tp5 was released from the colloidal PBCA-Tp5 NPs in 48 h. The proliferation test showed that PBCA-Tp5-NP had the similar effect as Tp5. The in vivo data showed that oral PBCA-Tp5-NPs had similar function as what intravenous Tp5 did. The oral bioavailability of Tp5 could be enhanced by PBCA nanoparticles. PBCA-Tp5-NP had the property of sustained-release and the efficacy of Tp5 was not changed after formulation. PMID- 17853431 TI - Characterization of micellar systems by the use of acoustic spectroscopy. AB - Acoustic spectroscopy affords a new and unique way to characterize concentrated suspension and emulsion while avoiding the limitations imposed by dilution, an undesirable step, particularly with highly structured samples. This study sought to illustrate the potentialities of this technique by using it to characterize the self-assembling behaviour of Poloxamer 407 systems (3-25%, w/v), both alone or after the addition of various amounts of hydroxypropyl beta-cyclodextrin (5 20%, w/v). Particle size and the microrheological extensional moduli (G' and G'') of the systems were determined from acoustic parameters such as sound attenuation and speed. By monitoring the variation of the particle size and the rheological extensional moduli at increasing temperatures, it was possible to define and outline the Poloxamer 407 transitions and the effect of the HP beta-CD on them. Poloxamer 407 micelle formation due to progressive dehydration occurred within a temperature interval of 15 degrees C (including gelation) and was dependent on poloxamer concentration. Particularly, particle size of the aggregates changed within this interval. Mean diameters were 600 nm at the onset of micelle formation and decreased after the thermogel formation to more or less 75 nm. The presence of HP beta-CD changed the basic self-assembling mechanism of Poloxamer 407 by increasing micelle formation and particularly thermogelation temperatures. The results confirm that acoustic spectroscopy offers a powerful method for characterizing heterogeneous systems, thus indicating its potential for applications in the pharmaceutical field. PMID- 17853432 TI - Liquid chromatography combined with mass spectrometry for 13C isotopic analysis in life science research. AB - Among the different disciplines covered by mass spectrometry, measurement of (13)C/(12)C isotopic ratio crosses a large section of disciplines from a tool revealing the origin of compounds to more recent approaches such as metabolomics and proteomics. Isotope ratio mass spectrometry (IRMS) and molecular mass spectrometry (MS) are the two most mature techniques for (13)C isotopic analysis of compounds, respectively, for high and low-isotopic precision. For the sample introduction, the coupling of gas chromatography (GC) to either IRMS or MS is state of the art technique for targeted isotopic analysis of volatile analytes. However, liquid chromatography (LC) also needs to be considered as a tool for the sample introduction into IRMS or MS for (13)C isotopic analyses of non-volatile analytes at natural abundance as well as for (13)C-labeled compounds. This review presents the past and the current processes used to perform (13)C isotopic analysis in combination with LC. It gives particular attention to the combination of LC with IRMS which started in the 1990's with the moving wire transport, then subsequently moved to the chemical reaction interface (CRI) and was made commercially available in 2004 with the wet chemical oxidation interface (LC IRMS). The LC-IRMS method development is also discussed in this review, including the possible approaches for increasing selectivity and efficiency, for example, using a 100% aqueous mobile phase for the LC separation. In addition, applications for measuring (13)C isotopic enrichments using atmospheric pressure LC-MS instruments with a quadrupole, a time-of-flight, and an ion trap analyzer are also discussed as well as a LC-ICPMS using a prototype instrument with two quadrupoles. PMID- 17853433 TI - Memory reconsolidation of cocaine-associated context requires nitric oxide signaling. AB - Recent studies suggest that long-term memory (LTM) is labile because retrieval of such memories may undergo a reconsolidation process which is vulnerable to disruption. Nitric oxide (NO) is a retrograde messenger involved in synaptic plasticity and LTM. In the present study the role of NO in reconsolidation of LTM of cocaine-associate context was investigated in wild type (WT) and neuronal nitric oxide synthase (nNOS) deficient mice (knockout; KO). LTM of cocaine associated context was established in both WT and nNOS KO mice by conditioned place preference learning. Subsequently, the retrieval of place preference in WT mice was challenged by either saline or the selective nNOS inhibitor 7 nitroindazole, and retrieval of place preference in KO mice was challenged by either saline or the NO-donor molsidomine. Results suggest that in the absence of nNOS activity, particularly during the reconsolidation phase, LTM of cocaine associated context is extinguished. PMID- 17853434 TI - The number of dopaminergic cells is increased in the olfactory bulb of monkeys chronically exposed to MPTP. AB - We investigated the impact of the nigrostriatal lesion on the olfactory tyrosine hydroxylase-immunoreactive (TH-ir) cells in monkeys. The majority of these TH-ir cells appeared in the glomerular layer of the olfactory bulb and many were immature but functional dopaminergic neurons. In parkinsonian monkeys the number of olfactory dopaminergic neurons increased up to 100% as compared to controls, but their phenotype did not change. This increased TH-ir cell population might be a direct consequence of the nigral cell loss and contribute to the hyposmia reported by Parkinson's disease patients. PMID- 17853435 TI - Antiparkinson therapeutic potencies correlate with their affinities at dopamine D2(High) receptors. AB - To determine whether antiparkinson dopamine agonists preferentially act on the high-affinity or the low-affinity states of dopamine D1 and D2 receptors, the agonist potencies were obtained by competition against [(3)H]SCH23390 for D1(High) and D1(Low), and against [(3)H]domperidone for D2(High) and D2(Low). N propylnorapomorphine and cabergoline were the most potent at D2(High), with dissociation constants of 0.18 and 0.36 nM, respectively. Other agonists had D2(High)K(i) values of 0.52 nM for quinagolide, 0.6 nM for (+)PHNO, 0.9 for bromocriptine, 1.8 nM for apomorphine, 2.4 nM for pergolide, 3 nM for quinpirole, and 6.2 nM for lergotrile. There was a clear correlation between the K(i) values at D2(High) and their therapeutic concentrations in the plasma water, as derived from the known concentrations after correction for the fraction bound to the human plasma proteins. The data suggest that D2(High) is the primary and common target for the antiparkinson action of dopamine agonists. Bromocriptine, cabergoline, lergotrile, pergolide, and pramipexole had no affinity for D1(High), consistent with the clinical observations that the D2-selective bromocriptine and pramipexole elicit low levels of dyskinesia. PMID- 17853436 TI - RNA-protein interactions and control of mRNA stability in neurons. AB - In addition to transcription, posttranscriptional mechanisms play a vital role in the control of gene expression. There are multiple levels of posttranscriptional regulation, including mRNA processing, splicing, editing, transport, stability, and translation. Among these, mRNA stability is estimated to control about 5-10% of all human genes. The rate of mRNA decay is regulated by the interaction of cis acting elements in the transcripts and sequence-specific RNA-binding proteins. One of the most studied cis-acting elements is the AU-rich element (ARE) present in the 3' untranslated region (3'UTR) of several unstable mRNAs. These sequences are targets of many ARE-binding proteins; some of which induce degradation whereas others promote stabilization of the mRNA. Recently, these mechanisms were uncovered in neurons, where they have been associated with different physiological phenomena, from early development and nerve regeneration to learning and memory processes. In this Mini-Review, we briefly discuss the general mechanisms of control of mRNA turnover and present evidence supporting the importance of these mechanisms in the expression of an increasing number of neuronal genes. PMID- 17853437 TI - Modulation of brain metabolism by very low concentrations of the commonly used drug delivery vehicle dimethyl sulfoxide (DMSO). AB - Dimethyl sulfoxide (DMSO) has long been used in studies as a vehicle to enhance the solubility and transport of ligands in biological systems. The effects of this drug on the outcomes of such studies are still unclear, with concentrations of DMSO reported as "safe" varying considerably. In the present work, we investigated the effects of very low concentrations of DMSO on the brain metabolism of [3-(13)C]pyruvate and D-[1-(13)C]glucose using (1)H/(13)C NMR spectroscopy and a guinea pig cortical brain slice model. Our results show that DMSO is accumulated by brain slices. DMSO at all concentrations [0.000025%-0.25% (v/v)] increased the metabolic rate when [3-(13)C]pyruvate was used as a substrate and also in the presence of D-[1-(13)C]glucose (0.00025%-0.1% DMSO). These results are consistent with DMSO stimulating respiration, which it may do through altering the kinetics of ATP-requiring reactions. Our results also emphasize that there is no practical concentration of DMSO that can be used in metabolic experiments without effect. Therefore, care should be taken when evaluating the actions of drugs administered in combination with DMSO. PMID- 17853438 TI - Differences among cell types in NAD(+) compartmentalization: a comparison of neurons, astrocytes, and cardiac myocytes. AB - Activation of the nuclear enzyme poly(ADP-ribose)-1 leads to the death of neurons and other types of cells by a mechanism involving NAD(+) depletion and mitochondrial permeability transition. It has been proposed that the mitochondrial permeability transition (MPT) is required for NAD(+) to be released from mitochondria and subsequently consumed by PARP-1. In the present study we used the MPT inhibitor cyclosporine-A (CsA) to preserve mitochondrial NAD(+) pools during PARP-1 activation and thereby provide an estimate of mitochondrial NAD(+) pool size in different cell types. Rat cardiac myocytes, mouse cardiac myocytes, mouse cortical neurons, and mouse cortical astrocytes were incubated with the genotoxin N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in order to activate PARP-1. In all four cell types MNNG caused a reduction in total NAD(+) content that was blocked by the PARP inhibitor 3,4-dihydro-5-[4-(1 piperidinyl)butoxy]-1(2H)-isoquinolinone. Inhibition of the mitochondrial permeability transition with cyclosporine-A (CsA) prevented PARP-1-induced NAD(+) depletion to a varying degree in the four cell types tested. CsA preserved 83.5% +/- 5.2% of total cellular NAD(+) in rat cardiac myocytes, 85.7% +/- 8.9% in mouse cardiac myocytes, 55.9% +/- 12.9% in mouse neurons, and 22.4% +/- 7.3% in mouse astrocytes. CsA preserved nearly 100% of NAD(+) content in mitochondria isolated from these cells. These results confirm that it is the cytosolic NAD(+) pool that is consumed by PARP-1 and that the mitochondrial NAD(+) pool is consumed only after MPT permits mitochondrial NAD(+) to exit into the cytosol. These results also suggest large differences in the mitochondrial and cytosolic compartmentalization of NAD(+) in these cell types. PMID- 17853439 TI - Dynamic features of postnatal subventricular zone cell motility: a two-photon time-lapse study. AB - Neuroblasts migrate long distances in the postnatal subventricular zone (SVZ) and rostral migratory stream (RMS) to the olfactory bulbs. Many fundamental features of SVZ migration are still poorly understood, and we addressed several important questions using two-photon time-lapse microscopy of brain slices from postnatal and adult eGFP(+) transgenic mice. 1) Longitudinal arrays of neuroblasts, so called chain migration, have never been dynamically visualized in situ. We found that neuroblasts expressing doublecortin-eGFP (Dcx-eGFP) and glutamic acid decarboxylase-eGFP (Gad-eGFP) remained within arrays, which maintained their shape for many hours, despite the fact that there was a wide variety of movement within arrays. 2) In the dorsal SVZ, neuroblasts migrated rostrocaudally as expected, but migration shifted to dorsoventral orientations throughout ventral regions of the lateral ventricle. 3) Whereas polarized bipolar morphology has been a gold standard for inferring migration in histologic sections, our data indicated that migratory morphology was not predictive of motility. 4) Is there local motility in addition to long distance migration? 5) How fast is SVZ migration? Unexpectedly, one-third of motile neuroblasts moved locally in complex exploratory patterns and at average speeds slower than long distance movement. 6) Finally, we tested, and disproved, the hypothesis that all motile cells in the SVZ express doublecortin, indicating that Dcx is not required for migration of all SVZ cell types. These data show that cell motility in the SVZ and RMS is far more complex then previously thought and involves multiple cell types, behaviors, speeds, and directions. PMID- 17853440 TI - Evidence for constitutive neural cell proliferation in the adult murine hypothalamus. AB - Compelling evidence suggests that the mammalian brain is capable of generating new neurons throughout adult life. While neurogenesis can be induced at various brain sites by exogenous cues, constitutive birth of new neurons has been unambiguously demonstrated within the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus. The lack of strong evidence that constitutive neurogenesis occurs elsewhere in the adult brain could be due to its exclusive restriction to the SVZ and SGZ or, for instance, to the inadequacy of the methods used to reveal new-born neurons at other brain sites. By using intracerebroventricular (icv) delivery of the mitotic marker bromodeoxyuridine (BrdU) we demonstrate that new cells are born continuously and in substantial numbers in the adult murine hypothalamus and that many of these cells appear to differentiate into neurons as assessed by the expression of doublecortin (Dcx) and other neuronal fate markers. As compared to intraperitoneal (ip) BrdU injections, central BrdU infusion also uncovers a higher-fold induction of hypothalamic cell proliferation by ciliary neurotrophic factor (CNTF). It appears that new cells are born throughout the hypothalamic parenchyma without an apparent restriction to a specific neurogenic layer, as seen in the SVZ. Thus, we provide evidence that the adult hypothalamus is constitutively neurogenic and that hypothalamic cell proliferation is highly responsive to mitogen action. PMID- 17853441 TI - Astrocyte membrane responses and potassium accumulation during neuronal activity. AB - Older studies suggest that astrocytes act as potassium electrodes and depolarize with the potassium efflux accompanying neuronal activity. Newer studies suggest that astrocytes depolarize in response to neuronal glutamate release and the activity of electrogenic glial glutamate transporters, thus casting doubt on the fidelity with which astrocytes might sense extracellular potassium rises. Any K(+)-induced astrocyte depolarization might reflect a spatial buffering effect of astrocytes during neuronal activity. For these reasons, we studied stimulus evoked currents in hippocampal CA1 astrocytes. Hippocampal astrocytes exhibited stimulus-evoked transient glutamate transporter currents and slower Ba(2+) sensitive inward rectifier potassium (K(ir)) currents. In whole-cell astrocyte recordings, Ba(2+) blocked a very weakly rectifying component of the astrocyte membrane conductance. The slow stimulus-elicited current, like measurements from K(+)-sensitive electrodes under the same conditions, predicted small bulk [K(+)](o) increases (<0.5 mM) following the termination of short-stimulus trains. These currents indicate the potential for astrocyte spatial K(+) buffering. However, Ba(2+) did not significantly affect resting [K(+)](o) or the [K(+)](o) rises detected by the K(+)-sensitive electrode. To test whether local K(+) rises may be significantly higher than those detected by glial recordings or by K(+) electrodes, we assayed EPSCs and fiber volleys, two measures very sensitive to K(+) increases. We found that Ba(2+) had little effect on neuronal axonal or synaptic function during short-stimulus trains, indicating that K(ir)s do not influence local [K(+)](o) rises enough, under these conditions to affect synaptic transmission. In conclusion, our results indicate that hippocampal astrocytes are faithful sensors of [K(+)](o) rises, but we find little evidence for physiologically relevant spatial K(+) buffering during brief bursts of presynaptic activity. PMID- 17853442 TI - Developmental mechanisms for retinal degeneration in the blind cavefish Astyanax mexicanus. AB - The sighted surface-dwelling (surface fish, SF) and the blind cave-living (cavefish, CF) forms of Astyanax mexicanus offer a unique opportunity to study the evolutionary changes in developmental mechanisms that lead to retinal degeneration. Previous data have shown the role of increased midline Sonic Hedgehog (Shh) signalling in cavefish eye degeneration (Yamamoto et al. [2004] Nature 431:844-847). Here, we have compared the major steps of eye development in SF and CF between 14 hours and 5 days of development. We have analyzed cell proliferation through PCNA and phospho-histone H3 staining and apoptosis through TUNEL and live LysoTracker analysis. We have assessed the expression of the major eye development signalling factors Shh and Fgf8, and the eye patterning genes Pax6, Lhx2, Lhx9, and Vax1, together with the differentiation marker GAD65. We show that eye development is retarded in CF and that cell proliferation in CF retina is proportionately similar to SF during early development, yet the retina degenerates after massive apoptosis in the lens and widespread cell death throughout the neuroretina. Moreover, and surprisingly, the signalling, patterning, and differentiation processes leading to the establishment of retinal layers and cell types happen almost normally in CF, although some signs of disorganization, slight heterochronies, and a lack of expression gradients are observable. Our data demonstrate that the evolutionary process of eye degeneration in the blind CF does not occur because of patterning defects of the retina and are consistent with the proposed scenario in which the trigger for eye degeneration in CF is lens apoptosis. PMID- 17853443 TI - Comparison of reflection contrast microscopy and electron microscopy on the histopathological diagnosis of various kidney diseases. AB - Our aim in this study was to compare reflection contrast microscopy (RCM) with transmission electron microscopy (TEM) to understand whether RCM could be used in the histopathological diagnosis of various kidney diseases as a less expensive and an easier alternative to TEM. The diagnoses of kidney pathologic lesions included Alport syndrome, thin membrane disease, Ig A nephropathy. RCM is a form of light microscope that works in the reflected mode, suitable to observe ultrathin (50-100 nm) plastic sections that is also used in TEM. Our findings showed that RCM showed similar results compared with TEM on these lesions described earlier. PMID- 17853444 TI - High-resolution water window X-ray imaging of in vivo cells and their products using LiF crystal detectors. AB - High contrast imaging of in vivo Chlorella sorokiniana cells with submicron spatial resolution was obtained with a contact water window X-ray microscopy technique using a point-like, laser-plasma produced, water-window X-ray radiation source, and LiF crystals as detectors. This novel type of X-ray imaging detectors is based on photoluminescence of stable electronic point defects, characterized by high intrinsic resolution. The fluorescence images obtained on LiF crystals exposed in single-shot experiments demonstrate the high sensitivity and dynamic range of this new detector. The powerful performances of LiF crystals allowed us to detect the exudates of Chlorella cells in their living medium and their spatial distribution in situ, without any special sample preparation. PMID- 17853445 TI - Chondrocytes interconnecting tracks and cytoplasmic projections observed within the superficial zone of normal human articular cartilage--a transmission electron microscopy, atomic force microscopy, and two-photon excitation microscopy studies. AB - The morphology of the normal human and rat articular cartilage was assessed using transmission electron microscopy (TEM), atomic force microscopy (AFM), and two photon excitation (2PE) microscopy. Spurr-embedded sections from fixed human cartilage were simultaneously evaluated using TEM and AFM. The presences of tracks among the chondrocytes from the superficial zone of the cartilage were observed. In order to ratify the presence of interconnecting tracks among superficial zone chondrocytes, whole fixed human and rat cartilage, as well as fresh whole rat cartilage, were examined under the 2PE. In all cases, these tracks were observed. In addition, porous matrix, well-defined lacunae, and cytoplasmic projections anchored to the extracellular matrix (ECM) were also detected. We conclude that normal human and rat flattened superficial chondrocytes might be interconnected by tracks running through the ECM. In addition, cytoplasmic projections were observed anchored to the ECM. All these structures may possibly be related to cell/cell and ECM/chondrocytes signaling. Our findings provide new information that possibly will be of relevant importance for a more profound study of normal cartilage physiology and eventually, the pathogenesis of osteoarthritis. PMID- 17853446 TI - Characterization of the melanin-concentrating hormone neurons activated during paradoxical sleep hypersomnia in rats. AB - Although the main nodes of the neuronal network that regulate paradoxical sleep (PS), also called rapid eye movement sleep, have been identified in rodents, it still needs to be more thoroughly described. We have recently shown that 58% of a hypothalamic neuronal population, the melanin-concentrating hormone (MCH) neurons, are activated after a PS hypersomnia and that MCH, when injected intracerebroventricularly, induces a dose-dependent increase in PS. This suggests that MCH plays a role in PS regulation. Two subpopulations of MCH neurons have been distinguished neurochemically, one that coexpresses cocaine and amphetamine regulated transcript (CART) and sends ascending projections to the septum and the hippocampus, the other, the non-CART MCH neurons, send descending projections to the lower brainstem and the spinal cord. In order to better characterize the PS activated MCH neurons it is interesting to determine whether they belong to the first, the second, or both subgroups. We therefore undertook an MCH, CART, and Fos triple immunolabeling study in PS hypersomniac rats. We showed that the MCH neurons activated during PS are part of both subpopulations since we found CART and non-CART MCH-activated neurons. Based on these results and the literature, we propose that MCH could be involved in memory processes and in the inhibition of muscle tone during PS. PMID- 17853447 TI - Comparative localization of cystathionine beta-synthase and cystathionine gamma lyase in retina: differences between amphibians and mammals. AB - Hydrogen sulfide (H(2)S) is a gaseous neuromodulator that can be synthesized by the transsulfuration enzymes cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CGL). In this study we examined H(2)S as a potential neuromodulator in vertebrate retina. CBS-like immunoreactivity (LI) was found in somas in the inner nuclear layer and as punctate staining in the inner and outer plexiform layers in the salamander retina. CGL-LI was most clearly characterized in salamander, where it was localized in Muller cells. Western blots indicated proteins with the correct molecular weights for both enzymes in both species for liver and cerebellum. Correct molecular weight proteins were identified for both CGL and CBS in salamander retina. The CBS antiserum did not recognize the correct molecular weight protein in mouse retina but the CGL antiserum recognized the correct molecular weight protein for mouse retina. Enzyme assays indicated both CGL and CBS enzyme activity in all three tissues in the salamander. There was good CBS activity in the liver and cerebellum of the mouse but no activity in the retina. CGL activity was clearly present only in the mouse liver, with only trace activity in the cerebellum and retina. In conclusion, both CBS and CGL are present in the amphibian retina, which suggests either a potential role for H(2)S as a gaseous neuromodulator in both neurons and glia in the retina or a requirement for cysteine and glutathione synthesis via the transsulfuration pathway as a defense against oxidative stress. PMID- 17853448 TI - Solvent effects in the slow dynamics of proteins. AB - The influence of solvent on the slow internal dynamics of proteins is studied by comparing molecular dynamics simulations of solvated and unsolvated lysozyme. The dynamical trajectories are projected onto the protein's normal modes in order to obtain a separate analysis for each of the associated time scales. The results show that solvent effects are important for the slowest motions (below approximately 1 ps(-1)) but negligible for faster motions. The damping effects seen in the latter show that the principal source of friction in protein dynamics is not the solvent, but the protein itself. PMID- 17853449 TI - The SKE-DOCK server and human teams based on a combined method of shape complementarity and free energy estimation. AB - We participated in rounds 6-12 of the critical assessment of predicted interaction (CAPRI) contest as the SKE-DOCK server and human teams. The SKE-DOCK server is based on simple geometry docking and a knowledge base scoring function. The procedure is summarized in the following three steps: (1) protein docking according to shape complementarity, (2) evaluating complex models, and (3) repacking side-chain of models. The SKE-DOCK server did not make use of biological information. On the other hand, the human team tried various intervention approaches. In this article, we describe in detail the processes of the SKE-DOCK server, together with results and reasons for success and failure. Good predicted models were obtained for target 25 by both the SKE-DOCK server and human teams. When the modeled receptor proteins were superimposed on the experimental structures, the smallest Ligand-rmsd values corresponding to the rmsd between the model and experimental structures were 3.307 and 3.324 A, respectively. Moreover, the two teams obtained 4 and 2 acceptable models for target 25. The overall result for both the SKE-DOCK server and human teams was medium accuracy for one (Target 25) out of nine targets. PMID- 17853451 TI - Docking with PIPER and refinement with SDU in rounds 6-11 of CAPRI. AB - Our approach to protein-protein docking includes three main steps. First we run PIPER, a new rigid body docking program. PIPER is based on the Fast Fourier Transform (FFT) correlation approach that has been extended to use pairwise interactions potentials, thereby substantially increasing the number of near native structures generated. The interaction potential is also new, based on the DARS (Decoys As the Reference State) principle. In the second step, the 1000 best energy conformations are clustered, and the 30 largest clusters are retained for refinement. Third, the conformations are refined by a new medium-range optimization method SDU (Semi-Definite programming based Underestimation). SDU has been developed to locate global minima within regions of the conformational space in which the energy function is funnel-like. The method constructs a convex quadratic underestimator function based on a set of local energy minima, and uses this function to guide future sampling. The combined method performed reliably without the direct use of biological information in most CAPRI problems that did not require homology modeling, providing acceptable predictions for targets 21, and medium quality predictions for targets 25 and 26. PMID- 17853450 TI - Novel distribution of junctional adhesion molecule-C in the neural retina and retinal pigment epithelium. AB - Junction adhesion molecules-A, -B, and -C (Jams) are cell surface glycoproteins that have been shown to play an important role in the assembly and maintenance of tight junctions and in the establishment of epithelial cell polarity. Recent studies reported that Jam-C mRNA was increased threefold in the all-cone retina of the Nrl(-/-) mouse, suggesting that Jam-C is required for maturation and polarization of cone photoreceptors cells. We examined the expression of Jams in the mouse retina by using confocal immunofluorescence localization. Jam-C was detected in tight junctions of retinal pigment epithelium (RPE) and at the outer limiting membrane (OLM) in the specialized adherens junctions between Muller and photoreceptor cells. Additionally, Jam-C labeling was observed in the long apical processes of Muller and RPE cells that extend between the inner segments and outer segments of photoreceptors, respectively. Jam-B was also detected at the OLM. In the developing retina, Jam-B and -C were detected at the apical junctions of embryonic retinal neuroepithelia, suggesting a role for Jams in retinogenesis. In eyes from Jam-C(-/-) mice, retinal lamination, polarity, and photoreceptor morphology appeared normal. Although Jam-A was not detected at the OLM in wild type retinas, it was present at the OLM in retinas of Jam-C(-/-) mice. These findings indicate that up-regulation of Jam-A in the retina compensates for the loss of Jam-C. The nonclassical distribution of Jam-C in the apical membranes of Muller cells and RPE suggests that Jam-C has a novel function in the retina. PMID- 17853452 TI - Displaced amacrine cells of the mouse retina. AB - The aim of this study was to characterize and classify the displaced amacrine cells in the mouse retina. Amacrine cells in the ganglion cell layer were injected with fluorescent dyes in flat-mounted retinas. Dye-filled displaced amacrine cells were classified according to dendritic field size, horizontal and vertical stratification patterns, and general morphology. We identified 10 different morphological types of displaced amacrine cell. Six of the cell types identified here are novel cell types that have not been described previously in the mouse retina, to the best of our knowledge. The displaced amacrine cells included four types of medium-field cells, with dendritic field diameters of 200 500 microm, and six types of wide-field cells, with dendritic fields extending over 500 microm. Narrow-field displaced amacrine cells, with dendritic field diameters smaller than 200 microm, were not encountered. The most frequently labeled displaced amacrine cell type was the starburst amacrine cell. At least three cell types identified here have nondisplaced counterparts in the inner nuclear layer as well. Displaced amacrine cells display a rich variety of stratification and branching patterns, which surely reflect the wide range of their functional roles in the processing of visual signals in the inner retina. PMID- 17853453 TI - Late-onset combined homocystinuria and methylmalonic aciduria (cblC) and neuropsychiatric disturbance. AB - We report on the case of a 36-year-old Hispanic woman with a spinal cord infarct, who was subsequently diagnosed with methylmalonic aciduria and homocystinuria, cblC type (cblC). Mutation analysis revealed c.271dupA and c.482G > A mutations in the MMACHC gene. The patient had a past medical history significant for joint hypermobility, arthritis, bilateral cataracts, unilateral hearing loss, anemia, frequent urinary tract infections, and mental illness. There was no significant past history of mental retardation, failure to thrive, or seizure disorder as reported in classic cases of cblC. Prior to the thrombotic incident, the patient experienced increased paresthesia in the lower extremities, myelopathy, and impaired gait. Given her previous psychiatric history, she was misdiagnosed with malingering until hemiplegia and incontinence became apparent. The authors would like to emphasize the recognition of a neuropsychiatric presentation in late onset cblC. Ten other reported late onset cases with similar presentations are also reviewed. PMID- 17853454 TI - Sibling phenotype concordance in classical infantile Pompe disease. AB - Pompe disease (acid-alpha-glucosidase deficiency) encompasses a clinical spectrum, ranging from severe infantile-onset disease with clinical symptoms appearing before 1 year of age with rapid progression to an early death, to late onset disease with a much more variable age at onset and disease course. Sibling phenotype discordance has been reported for late-onset Pompe disease, but has not been studied in classical infantile disease. We reviewed the medical literature for affected sibships in which at least one sibling had clinical and pathology or biochemical findings consistent with infantile Pompe disease including symptoms beginning in infancy, early hypotonia, cardiomegaly documented by 6 months of age, and early death. The age at symptom onset, age at death, and clinical course were compared between probands and affected siblings. Our results showed that since 1931, publications document 13 families with 31 affected infants (11 probands; 20 affected siblings). The median age at symptom onset for all affected infants was 3 months (range 0-6 months) with significant correlation (R = 0.60, P = 0.04) between probands and affected siblings. The median age at death for all affected infants was 6 months (range 1.5-13 months); probands were slightly older at death than their siblings. The median length of disease course for all affected infants was 3 months (0-10 months) and was slightly longer for probands. Unlike late-onset Pompe disease, there appears to be minimal phenotypic and lifespan variation among siblings with infantile Pompe disease. This prognostic information is vital for families with affected infants and allows for appropriate genetic counseling. PMID- 17853455 TI - A boy with severe craniodiaphyseal dysplasia and apparently normal mother. AB - We describe a boy and his mother affected with craniodiaphyseal dysplasia (CDD). The boy had a very severe form of the disease with extensive osteosclerosis already at birth. Facial diplegia, bilateral hearing loss and optic nerve atrophy were early, severe complications of the disease. At age 7 years progressive genu valgum and unusual epimetaphyseal radiographic appearances suggested hyperparathyroidism. This was confirmed by biochemical tests. Because of some facial similarity between the asymptomatic mother and the propositus, a limited skeletal survey of the mother was performed. It demonstrated cranial osteosclerosis and hyperostosis. It is possible that the mother has somatic mosaicism for a mutation of the genes causing CDD. PMID- 17853456 TI - Pseudo-Bartter syndrome due to Hirschsprung disease in a neonate with an extra ring chromosome 8. PMID- 17853458 TI - Tibial agenesis and Gollop-Wolfgang complex. PMID- 17853459 TI - Trisomy of 19.4 Mb region of chromosome 22 and subtelomeric 17p identified in a male without clinical affectation. AB - Supernumerary marker chromosomes (SMCs) have a reported frequency in the prenatal and newborn population ranging from 0.04% to 0.08% and about 37% of diagnosed SMCs are associated with an abnormal phenotype. Around 7.5% of them are derived from chromosome 22. SMCs(22) that result in tri- or tetrasomy of band 22q11.2 are associated with Cat-eye syndrome (CES), a syndrome of variable penetrance and affectation. CES-like phenotype has been also related to 22q11.2 interstitial duplications and der(22) syndrome. The 22q11.2 region, also involved in the velocardiofacial microdeletional syndrome, presents high susceptibility to chromosomal rearrangements due to the presence of low-copy repeats sequences (LCR22). Another region in the genome rich in LCR is 17p and five recurrent disorders have been mapped on the region 17p11-p13. Some chromosomal imbalances affecting the 17p13.3 subtelomeric region have been reported, related to cryptic unbalanced translocations and associated, in most cases, to mental retardation and dysmorphic features. We report on a healthy male carrier of a SMC that was identified as a +der(22)t(17;22)(p13.3;q11.2) consequence of an abnormal 3:1 segregation of the paternal t(17;22) and we have determined the approximate size of the trisomic regions, comparing the obtained results with other reported imbalances involving 22q11.2 and 17pter. PMID- 17853460 TI - Atypical breakpoints generating mosaic interstitial duplication and triplication of chromosome 15q11-q13. PMID- 17853461 TI - MYO15A (DFNB3) mutations in Turkish hearing loss families and functional modeling of a novel motor domain mutation. AB - Myosin XVA is an unconventional myosin which has been implicated in autosomal recessive nonsyndromic hearing impairment (ARNSHI) in humans. In Myo15A mouse models, vestibular dysfunction accompanies the autosomal recessive hearing loss. Genomewide homozygosity mapping and subsequent fine mapping in two Turkish families with ARNSHI revealed significant linkage to a critical interval harboring a known deafness gene MYO15A on chromosome 17p13.1-17q11.2. Subsequent sequencing of the MYO15A gene led to the identification of a novel missense mutation, c.5492G-->T (p.Gly1831Val) and a novel splice site mutation, c.8968-1G- >C. These mutations were not detected in additional 64 unrelated ARNSHI index patients and in 230 Turkish control chromosomes. Gly1831 is a conserved residue located in the motor domains of the different classes of myosins of different species. Molecular modeling of the motor head domain of the human myosin XVa protein suggests that the Gly1831Val mutation inhibits the powerstroke by reducing backbone flexibility and weakening the hydrophobic interactions necessary for signal transmission to the converter domain. PMID- 17853462 TI - Two novel GALNT3 mutations in familial tumoral calcinosis. AB - Familial tumoral calcinosis (TC) is characterized by elevated serum phosphate concentrations, normal or elevated 1,25(OH)2 vitamin D, as well as periarticular and vascular calcifications. Recessive mutations in the mucin-like glycosyltransferase GalNAc transferase-3 (GALNT3) and the phosphaturic hormone fibroblast growth factor-23 (FGF23) have been shown to result in TC. In the present study, mutational analyses were performed on two patients with TC to determine the molecular basis of their diseases. Analysis of the first patient revealed a novel, homozygous base insertion (1102_1103insT) in GALNT3 exon 5 that results in a frameshift and premature stop codon (E375X). The second patient had a novel homozygous transition (1460 g>a) in GALNT3 exon 7, which caused a nonsense mutation (W487X). Both mutations are predicted to markedly truncate the mature GALNT3 protein product. Although the patients carry GALNT3 mutations, these individuals presented with low-normal serum concentrations of intact biologically active FGF23 and high levels of C-terminal FGF23. In order to discern a possible relationship between GALNT3 and FGF23 in TC, a comprehensive assessment of the reported TC mutations was also performed. In summary, we have detected novel GALNT3 mutations that result in familial TC, and show that disturbed serum FGF23 concentrations are present in our TC cases as well as in previously reported cases. These studies expand our current genetic understanding of familial TC, and support a pathophysiological association between GALNT3 and FGF23. PMID- 17853463 TI - Treatment with antiparkinson and antidepressant drugs: a register-based, pharmaco epidemiological study. AB - Depressive symptoms and major depression are frequent in patients with Parkinson's disease (PD). However, a systematic knowledge about the treatment with antidepressant drugs among PD patients is missing. We estimated the frequency of antidepressant drug treatment in a national sample of persons treated with antiparkinson drugs (APDs). All persons treated with APDs were identified in the national Danish Prescription database. The subsequent risk of treatment with antidepressants was estimated and compared with the risks for two large control groups. The study period was 5 years. In total, 1,029,737 persons were included. Persons who got APDs had significantly increased rate ratios (RR) of subsequent antidepressant drug treatment compared with an unexposed control group (RR: 2.10 (95% CI: 2.04-2.16)) and with persons who got anti-diabetic drugs [RR: 1.58 (95% CI: 1.51-1.65)]. Persons treated with APDs have higher frequency of antidepressant drug treatment than have controls. With the reservation that data on drug consumption cannot be directly transferred into conclusions about specific diseases, the present study supports results from other population-based studies of an association between PD and depression. PMID- 17853464 TI - Aggressive natural killer cell leukemia presenting with hemophagocytic lymphohistiocytosis. AB - Aggressive natural killer cell leukemia (ANKL) is a very rare condition and when reported occurs almost exclusively in adults. We report a pediatric case of ANKL that presented with hemophagocytic syndrome, preceding the onset of leukemia by 12 weeks. Clinical and laboratory findings are discussed, along with morphology, immunophenotyping and cytogenetics, as well as the association with Epstein-Barr virus (EBV). This case is noteworthy for the expression of CD8 on the malignant cells, the cytogenetic findings that include abnormalities of chromosomes 6 and 7, as well as the age of the patient. PMID- 17853465 TI - Longitudinal assessment of immunological status and rate of immune recovery following treatment in children with ALL. AB - BACKGROUND: We prospectively evaluated the immunological status, immune recovery and risk of infection in pediatric ALL patients treated on the BFM 95 protocol. PROCEDURE: Humoral and cellular immunity were evaluated in 72 children with ALL at the end of intensive therapy and values were compared to those at the completion of therapy and 6-monthly. Parameters investigated included lymphocyte subpopulation by flow cytometry, immunoglobulin levels by nephelometry, antibody titers to previous immunizations and delayed hypersensitivity with skin testing. Immune responses were correlated to duration of therapy, CNS radiotherapy, age and sex. RESULTS: Humoral immunity was severely depressed by the end of intensive therapy with low immunoglobulin levels and CD19, improved after therapy cessation. Cellular immune responses were normal at the end of intensive treatment but declined significantly by the end of therapy and both CD4 and CD8 remained low at later evaluation points whereas CD4/CD8 ratio was increasing. Duration of therapy and CNS radiotherapy did not affect the rate of immune recovery whereas female had higher CD19, CD45RO, and IgM and children >7 years had higher CD19 and lower CD16 and CD3DR. Among immunized children, 86.7% maintained protective antibodies to MMR and 63% to polio. Despite impairment of immunity, infections outside the neutropenic periods were common viral illnesses. CONCLUSION: Humoral immunity was depressed in children with ALL at the end of intensive therapy but began to recover after cessation of therapy. In contrast, cellular immunity declined significantly by the end of therapy and remained abnormal for at least 1 year post-therapy. PMID- 17853466 TI - Studies of age-correlated features of cognitive-behavioral development in children and adolescents with genetic disorders. AB - Studies of age-related features of cognitive-behavioral deficits produced by genetic mutations permit us to draw inferences about how brain development may be related cognitive ability as the child ages. Except for Down syndrome (DS) and the fragile X mutation (FRAXA), little is known about the longitudinal changes in cognitive-behavioral development in individuals with genetic abnormalities producing learning disabilities (LD) or mental retardation (MR). The purpose of this prospective study was to compare and contrast age related to cognitive abilities, adaptive and maladaptive behaviors in children and adolescents in the same age range, diagnosed with one of three genetic disorders: the FRAXA mutation, Neurofibromatosis type 1 (NF1) or Williams-Beuren syndrome (WBS). We also sought to examine whether cognitive-behavioral abilities associated with these three genetic disorders were related systematically to age. We examined 108 children, ages 4-15 years, with FRAXA, WBS, or NF1. Results show that there is a significant negative correlation between age and IQ, and between age and adaptive behavior (DQ) scores, in children with FRAXA and WBS, but not in children with NF1. All three groups of children have unusually high proportions of maladaptive behavior, ranging from 1/6 children with NF1 to 2/3 children with FRAXA. Cognitive and adaptive behavior profiles of children with FRAXA and WBS were also surprisingly similar. Our findings suggest the need for examining longitudinal developmental cognitive-behavioral changes in children and adolescents with all genetic disorders that produce LD or MR. PMID- 17853467 TI - Conorenal dysplasia: a syndrome of cone-shaped epiphysis, renal disease in childhood, retinitis pigmentosa and abnormality of the proximal femur. AB - Conorenal dysplasia is a rare syndrome which includes cone shaped epiphysis, renal disease in childhood, retinitis pigmentosa and abnormality of the proximal physis and metaphysis of the femur. A long term followup of one patient is presented along with a review of the reported cases. PMID- 17853468 TI - Periconceptional consumption of vitamins containing folic acid and risk for multiple congenital anomalies. AB - Although it has been well established that periconceptional use of multivitamins containing folic acid (FA) reduces the risk for neural tube defects, two recent U.S. studies have shown an increased risk for multiple congenital anomalies (MCAs) associated with periconceptional use of vitamins containing FA. This study assessed the association between the periconceptional use of vitamins containing FA and MCAs in a third U.S. population. Mothers of infants with MCAs and a random sample of live births (control infants) born in Iowa during 1993-1995 were eligible to participate in the Birth Defects Risk Factor Surveillance case control study. During a telephone interview, participants reported on exposure to FA through vitamins, cereal, and food supplements. There was no association between taking vitamins containing FA during the periconceptional period (3 months before conception through the first trimester) and MCAs in the crude estimates or after adjusting for maternal race or ethnicity, education, gravidity, smoking, or alcohol use in the first trimester, or body mass index prior to pregnancy [adjusted odds ratio (aOR)=1.12, 95% confidence interval (CI) 0.75-1.69]. There was also no association between vitamin exposure beginning in the first trimester and MCAs outcome (aOR=1.05, 95% CI 0.59-1.87). In contrast to the two recently published reports, there was no association between periconceptional vitamin exposure and MCAs in the Iowa population. PMID- 17853469 TI - Evaluation of a commercially available focused aCGH platform for the detection of constitutional chromosome anomalies. AB - Microarray-based comparative genomic hybridization (aCGH) allows for simultaneous high-resolution analysis of multiple genomic loci. Recently, focused aCGH platforms have emerged allowing for analysis of numerous clinically relevant chromosome loci. The purpose of our study was to evaluate the Spectral Genomics Constitutional Chip 1.0 (CC) for use in the clinical laboratory. The CC consisted of 429 BAC clones for 41 known genetic deletion/duplication syndromes, subtelomeric regions, and chromosomal backbone clones. We conducted a blinded study of 48 samples including 46 patients (one sample was run in triplicate) with previously determined constitutional chromosome anomalies and two negative controls. Patient samples included 31 microdeletions, four duplications, three derivative chromosomes, three trisomies, and five sex chromosome aneuploidies. Our results show that the CC identified the expected gains and/or losses in 46 of 48 samples. The two negative controls were considered to be normal and the three replicates of the same patient sample were concordant. Two samples yielded false negative results; however, repeat analysis produced acceptable results for one of them. One sample ultimately had an insufficient amount of DNA precluding aCGH analysis. While promising, the results suggest that further studies are needed to reduce protocol variability and to establish standard analysis and interpretation criteria. Further, this study verifies the importance of extensive validation studies prior to clinical implementation of new clinically available methodologies. PMID- 17853470 TI - Lymphedema, cardiac septal defects, and characteristic facies: possible new case of Irons-Bianchi syndrome. AB - We describe a Dutch girl with fetal hydrops, congenital lymphedema of the lower legs, complex congenital cardiac malformation, and a typical face with epicanthal folds. This particular combination of symptoms has been previously described by Irons and Bianchi in 1996. Our report confirms their observation and suggests that this particular constellation of symptoms may constitute a new syndrome. Molecular analysis confirms this statement by demonstrating absence of mutations in several genes known to be involved in syndromes with lymphedema. PMID- 17853471 TI - PAK3 related mental disability: further characterization of the phenotype. AB - We report clinical, neuropsychological and molecular findings in affected males and carrier females in the fourth reported family with mental retardation caused by mutation in the PAK3 gene (Xq22.3-q23), W446S. In contrast to previous reports, carrier females manifested learning problems and mild mental disability. Skewed X-inactivation was observed here for the first time in carriers of PAK3 mutation. Neuropsychological tests in affected males and carrier females suggested a common neuropsychological profile of impaired spatial cognitive abilities and defects in attentional and executive functions. The five affected males examined herein had a proportionally small head size or microcephaly, large ears, oral motor hypotonia with drooling and inarticulate speech and short attention span, anxiety, restlessness, and aggression. Brain imaging showed signs of chronic non-progressive hydrocephalus in one patient who manifested psychosis and fluctuant gait deterioration, while two other patients showed no abnormalities. EEG recordings were available from four affected males and one carrier female, and all showed similar posterior slow wave activity without epileptic discharges. Only one affected male in the family suffered from epilepsy. When comparing the affected males in this family and the three previously reported families with mental retardation due to a PAK3 mutation, similarities in their characteristics were small head size or microcephaly, large ears, speech defects, behavioral abnormalities, and psychiatric disease. PMID- 17853472 TI - An innocuous duplication of 11.2 Mb at 13q21 is gene poor: sub-bands of gene paucity and pervasive CNV characterize the chromosome anomalies. AB - A boy with autistic spectrum disorder without dysmorphisms was found to have a chromosome duplication of part of band 13q21. His mother and grandfather both of normal intellect had the same chromosomal duplication. Comparison was made with the Chromosome anomaly database www.som.soton.ac.uk/research/geneticsdiv/anomaly%20register which revealed similar cases. Mapping on DNA microarray for the proband and mother showed the duplication to be of length 11.2 Mb, encompassing the 13q21.1-13q21.32 region. The duplicated region is profoundly gene poor, with a mean gene density of 0.45 genes/Mb. We estimate, that the mean gene density in the sub-bands of the chromosome anomalies is 2.4-2.5 genes/Mb. In addition the percentages of the sub bands reported as copy number variants (CNV) was estimated from the Database of Chromosome Genomic Variants (http://projects.tcag.ca/variation/). It was found that for some of these sub-bands, gene paucity was likely to be a major contributor to their innocuous phenotypic effect, for example, the gene densities were for: 1p31.2 (1.25 genes/Mb); 2p12 (1.7); 4p15.31 (1.3); 5p14.1 (0.22); 5p14.3 (0.8); 5q21.2 (0.6); 5q21.3 (1.2); 8p23.2 (0.25); 13q21.1 (0.9); 14q31.1 (1.4); 18q22.1 (1.4); 21q21.1 (1.2); and 21q21.2 (0.7). For other sub-bands the percentage of the band in which CNV have been reported was found to be markedly increased, for example, 8p23.2 (94.7% of the band is defined by reported CNV); 3p26.3 (81.6); 5p14.3 (59.3); 8p22 (48.8); 2p12 (44.0); 5q21.1 (43.6); 6q24.2 (41.4); 9p23 (38.8); 10q21.1 (36.5); 5q21.2 (35.4), and 11q14.3 (33.8). We argue that both gene paucity and pervasive CNV are major indicators of bands conforming to the Chromosome Anomaly phenomenon. PMID- 17853473 TI - Further refinement of the candidate region for monosomy 9p syndrome. PMID- 17853474 TI - Trisomy 2 mosaicism in hypomelanosis of Ito. PMID- 17853475 TI - The origin of trisomy 13. AB - Trisomy 13 is one of the most common trisomies in clinically recognized pregnancies and one of the few trisomies identified in liveborns, yet relatively little is known about the errors that lead to trisomy 13. Accordingly, we initiated studies to investigate the origin of the extra chromosome in 78 cases of trisomy 13. Our results indicate that the majority of cases (>91%) are maternal in origin and, similar to other autosomal trisomies, the extra chromosome is typically due to errors in meiosis I. Surprisingly, however, a large number of errors also occur during maternal meiosis II ( approximately 37%), distinguishing trisomy 13 from other acrocentric and most nonacrocentric chromosomes. As with other trisomies, failure to recombine is an important contributor to nondisjunction of chromosome 13. PMID- 17853476 TI - Fetal anticonvulsant syndromes and polymorphisms in MTHFR, MTR, and MTRR. AB - The malformations found in fetal anticonvulsant syndromes (FACS) are associated with folic acid deficiency and methylene-tetrahydrofolate reductase (MTHFR) polymorphisms in the general population. To investigate a possible association between FACS and MTHFR genotype, we recruited 200 mothers who had taken anti epileptic drugs in pregnancy, and delivered at Aberdeen Maternity Hospital over a 26-year period. Clinical findings in the mothers and their 337 children were documented. A clinical algorithm was devised to diagnose FACS objectively. Case parent triads were genotyped for polymorphisms in MTHFR, serine hydroxymethyl transferase (SHMT1), methionine synthase (MTR), and methionine synthase reductase (MTRR), and analyzed by log-linear regression. No effect of the child's genotype on congenital malformation, neurodevelopmental disorder or FACS was detected using this method. The risk of having a child with congenital malformation or FACS was three to four times higher for mothers who were MTHFR 677TT homozygotes compared with MTHFR 677CC homozygotes. MTR 2756A > G and MTRR 66A > G genotype frequencies in children with FACS and neurodevelopmental disorder were different from those in healthy blood donor controls. PMID- 17853478 TI - Neuroimaging follow-up in a case of Rasmussen's encephalitis with dyskinesias. AB - We describe a case of adult-onset biphasic Rasmussen's encephalitis who presented seizures and left dyskinesias at the onset and, after 1 year, language disorder. Serial MRI and [(18)F] FDG-PET scans were performed showing involvement of the right cerebral hemisphere in the first phase and of the contralateral one in the second. PMID- 17853477 TI - Microglial activation mediates neurodegeneration related to oligodendroglial alpha-synucleinopathy: implications for multiple system atrophy. AB - The role of microglial activation in multiple system atrophy (MSA) was investigated in a transgenic mouse model featuring oligodendroglial alpha synuclein inclusions and loss of midbrain dopaminergic neurons by means of histopathology and morphometric analysis. Our findings demonstrate early progressive microglial activation in substantia nigra pars compacta (SNc) associated with increased expression of iNOS and correlating with dopaminergic neuronal loss. Suppression of microglial activation by early long-term minocycline treatment protected dopaminergic SNc neurons. The results suggest that oligodendroglial overexpression of alpha-synuclein may induce neuroinflammation related to nitrosive stress which is likely to contribute to neurodegeneration in MSA. Further, we detected increased toll-like receptor 4 immunoreactivity in both transgenic mice and MSA brains indicating a possible signaling pathway in MSA which needs to be further studied as a candidate target for neuroprotective interventions. PMID- 17853479 TI - Osteoinductive effect of bone bank allografts on human osteoblasts in culture. AB - Incorporation of a human bone allograft requires osteoclast activity and growth of recipient osteoblasts. The aim of this work was to study the effects produced by autoclavated and -80 degrees C frozen bone allografts on osteoblast proliferation and synthesis of interleukin 6 (IL6), activator of bone resorption, aminoterminal propeptide of procollagen I (PINP), marker of bone matrix formation, and osteoprotegerin (OPG), inhibitor of osteoclast activity and differentiation. Allografts were obtained from human femoral heads. Human osteoblasts were cultured in the presence (problem group) or in the absence (control group) of allografts during 15 days. Allografts produced a decrease in osteoblast proliferation in the first week of the experiment, and an increase in IL6 mRNA, both at 3 h and 2 days, and an increase in the IL6 released to the culture medium the second day of the experiment. We found a decrease in OPG released to the culture on the 2nd and fourth days. These results suggest an increase in bone resorption and a decrease in bone formation in the first week of the experiment. In the second week, allografts produced an increase in osteoblast proliferation and PINP release to the culture medium, indicating an increase in bone formation; an increase in OPG released to the culture medium, which would indicate a decrease in bone resorption; and a decrease in IL6, indicating a decrease in bone resorption stimulation. These results demonstrate that autoclavated and -80 degrees C frozen bone allografts produce in bone environment changes that regulate their own incorporation to the recipient bone. PMID- 17853480 TI - WT1 mutations in Meacham syndrome suggest a coelomic mesothelial origin of the cardiac and diaphragmatic malformations. AB - Meacham syndrome is a rare sporadically occurring multiple malformation syndrome characterized by male pseudohermaphroditism with abnormal internal female genitalia comprising a uterus and double or septate vagina, complex congenital heart defect and diaphragmatic abnormalities. We report on eight new cases of this condition, two of whom were shown to have heterozygous missense mutations in the C-terminal zinc finger domains of WT1: Arg366Cys and Arg394Trp. These data represent clinical and molecular evidence that the WT1 gene plays a central role in normal development of the diaphragm and the proepicardially derived tissues. Identification of WT1 expression in the region of coelomic mesothelium which will form the proepicardium and diaphragm provides a plausible unifying patterning defect in these cases. Interestingly, the Arg366Cys mutation has been previously reported in Denys-Drash syndrome and Arg394Trp mutation has been previously reported in both isolated Wilms tumor and Denys-Drash syndrome. This phenotypic diversity with a single mutation suggests there are other factors modulating all aspects of WT1 function during human development. If genetic modifiers of WT1 can be identified in animal models these become good candidate genes for the cases with Meacham syndrome we report on here where WT1 mutations cannot be identified. PMID- 17853481 TI - Zonisamide in patients with essential tremor and Parkinson's disease. PMID- 17853482 TI - Height as a potential indicator of early life events predicting Parkinson's disease: a case-control study. AB - Aim of this study was to investigate the relationship between height in young adult age and Parkinson's disease (PD) risk. We included 266 persons affected by idiopathic PD. Patients were matched by age and sex to 266 controls by a random selection from the municipality of residence. We collected information about height preceding PD from official documents where these characteristics referred to young adult age (nearly 30 years). We compared height in cases and controls by calculating differences in mean distribution and by chi(2) analyses. Crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression models. Mean height was significantly lower in persons affected by PD compared to controls (P = 0.03). Difference was significant only in men (P = 0.001). Logistic regression models showed an inverse association between height and PD (OR 0.35; CI 0.16, 0.79; P < 0.01 comparing individuals in the highest percentiles of height with those in the lowest). Our results indicate an association between height and PD in men. Considering that dopamine sensitivity in the hypothalamic-pituitary axis is related to adult height, our findings suggest a relationship between PD and factors modulating somatic growth early in life. PMID- 17853483 TI - Antero-ventral internal pallidum stimulation improves behavioral disorders in Lesch-Nyhan disease. AB - The Lesch-Nyhan syndrome is an X-linked recessive disorder caused by a deficiency in hypoxanthine-guanine phosphoribosyl transferase, a purine salvage enzyme. Affected individuals exhibit a characteristic neurobehavioral disorder with delayed acquisition of motor skills, dystonia, severe self-mutilations, and aggressive behavior. Deep brain stimulation has been previously proposed for controlling isolated involuntary movements and psychiatric disorders. We applied a double bilateral simultaneous stimulation to limbic and motor internal pallidum in one patient for controlling both behavioral and movement disorders, respectively. The injurious compulsions disappeared; dystonia and dyskinesia were decreased at 28 months follow-up. PMID- 17853484 TI - Pupil diameter in darkness differentiates progressive supranuclear palsy (PSP) from other extrapyramidal syndromes. AB - The most important features that characterize and differentiate progressive supranuclear palsy from other Parkinsonian syndromes are postural instability, supranuclear gaze palsy, pseudobulbar palsy, parkinsonism, and cognitive disturbances. In this article, we demonstrate that progressive supranuclear palsy patients exhibit pathologically decreased pupil diameters after dark adaptation recorded by TV pupillography. A cut off value of 3.99 mm was defined to differentiate progressive supranuclear palsy patients from patients with other extrapyramidal disorders like Parkinson's disease and multiple system atrophy with a specificity of 86.4% and a sensitivity of 70.8%. Other pupil abnormalities could not be described in patients with extrapyramidal syndromes. PMID- 17853485 TI - A novel injectable scaffold for cartilage tissue engineering using adipose derived adult stem cells. AB - Articular cartilage has a limited self-regenerative capacity. Thus, treatment of cartilage lesions is a major challenge. Tissue engineering using a variety of biomaterials is a promising solution to the problem of cartilage damage. In this in vitro study, we investigated the effect of the presence of cartilage-tissue chondroitin-sulfate (CS) in a fibrin scaffold on the differentiation of adipose derived adult stem cells (ADAS cells) into chondrocytes. Isolated rabbit ADAS cells were cultured in fibrin matrices with and without CS for up to 14 days. ADAS cells differentiated into chondrocytes in both matrices, but cell proliferation, glycoaminoglycans content, and type II collagen expression were significantly higher in the fibrin-CS matrices than those in the fibrin matrices alone. Histological examination and scanning electronic microscopy revealed the fibrin-CS matrices exceeded in inducing differentiation of ADAS cells into chondrocytes in terms of tissue morphological characteristics. We concluded that the fibrin-CS matrices mimicking native cartilage extracellular matrix could act as a three-dimensional scaffold for cartilage tissue engineering and have the potential for promoting ADAS cells differentiation into chondrocytes. PMID- 17853486 TI - Craniofacioskeletal syndrome: an X-linked dominant disorder with early lethality in males. AB - A syndrome with multisystem manifestations has been observed in three generations of a Caucasian family. The findings in seven females provide a composite clinical picture of microcephaly, short stature, small retroverted ears, full tip of the nose overhanging the columella, short philtrum, thin upper lip, soft tissue excrescences at the angle of the mouth, small mandible, small hands and feet with brachydactyly, finger V clinodactyly, flat feet, an excessive number of fingerprint arches, and mild impairment of cognitive function. Two males were more severely affected and died in the initial months of life. They showed intrauterine growth retardation, broad cranium with wide sutures and fontanelles, cardiac defects, small hands and feet with abnormal digital creases and small nails, and genital abnormalities. The affected males had low serum calcium in the neonatal period. Serum calcium, phosphorous, and parathormone levels in the females were normal. Radiographs showed cortical thickening of the long bones, underdevelopment of the frontal sinuses, narrow pelvis and hypoplasia of the middle phalanx of finger five. MRI of the brain showed slightly reduced brain volumes and an extra gyrus of the superior temporal region. X-inactivation studies showed near complete skewing in two affected females, but were not informative in three others. X-linkage as the mode of inheritance is proposed on the basis of different severity in males/females, complete skewing of X inactivation in informative females, and a lod score (1.5) suggestive of linkage to markers in Xq26-q27. PMID- 17853487 TI - Clinical phenotype of lathosterolosis. AB - Lathosterolosis (LS) is a defect of cholesterol biosynthesis due to the deficiency of the enzyme sterol-C5-desaturase. Only two patients have been described to date, both presenting with multiple malformations, mental retardation, and liver involvement. In addition in one of them pathological examination revealed mucolipidosis-like inclusions on optic microscopy analysis, and peculiar lysosomal lamellar bodies on electron microscopy analysis. This study is focused on a better characterization of the clinical phenotype of LS. We describe a further case in a fetus, sibling of the first patient reported, presenting with neural tube defect, craniofacial and limb anomalies, and prenatal liver involvement. The fetal phenotype suggests the possible occurrence of significant intrafamilial variability in LS, and expands the phenotypic spectrum of the disease. Histological examination of autopsy samples from the fetus and skin fibroblasts from the living sibling suggested that the mucolipidosis-like picture previously reported is not a constant feature of LS, being possibly associated with the most severe biochemical defects, but confirmed the ultrastructural finding of lamellar inclusions. The LS phenotype appears to be characterized by the distinctive association of a recognizable pattern of congenital anomalies, involving axial and appendicular skeleton, liver, central nervous and urogenital systems, and lysosomal storage. This condition partially overlaps with other defects of sterol metabolism, suggesting intriguing pathogenic links among these conditions. PMID- 17853488 TI - Recurrent inverted duplication of 2p with terminal deletion in a patient with the classical phenotype of trisomy 2p23-pter. AB - Inverted duplications with terminal deletions have been reported in an increasing number of chromosomes and are probably more frequent than suspected until recently. We describe the cytogenetic and molecular characterization of an inverted duplication of chromosome 2p in an 8-year-old girl. Firstly interpreted as partial duplication 2p, the rearrangement was in fact an inverted duplication associated with a terminal deletion of the short arm of the rearranged chromosome 2, the latter not being detectable by cytogenetic analysis. The complete karyotype was: 46,XX,add(2)(p23)dn.ish inv dup del(2)(:p23.2-->p25.3::p25.3- >qter) (wcp2+,N-MYC++,2pter-)dn. We precisely define the extension of both the duplication and the deletion using bacterial artificial chromosomes clones spanning the regions. The size of the inverted duplicated segment was estimated to be 28 Mb, spanning from 2p23.2 to 2p25.3, and an approximately 1.6 Mb segment at 2pter-p25.3 was deleted in the abnormal chromosome. The physical findings noted in our patient include prominent forehead, hypertelorism, flat nasal bridge, and low-set and large ears. In addition, she had congenital heart defect and scoliosis. Her psychomotor development was severely delayed from the beginning. All these clinical features are the same as observed for the typical trisomy 2p23-pter syndrome. The phenotypic effects of the terminal deletion of 2p in addition to the trisomy are discussed. This is the third patient presenting with a severe clinical phenotype and a de novo inv dup del (2p). PMID- 17853489 TI - "Recumbent" gait: relationship to the phenotype of "astasia-abasia"? AB - Psychogenic gait disorders can present in many different ways. Among patients with a pure psychogenic gait disorder, buckling of the knee is the most common feature, followed by astasia-abasia. Here, we describe one such patient with a very unusual gait disturbance that might be regarded as a variant of astasia abasia. The patient characteristics are described and discussed in a historical context. PMID- 17853490 TI - Myoclonus-dystonia syndrome: clinical presentation, disease course, and genetic features in 11 families. AB - Myoclonus-dystonia syndrome (MDS) is an inherited movement disorder with clinical and genetic heterogeneity. The epsilon sarcoglycan (SGCE) gene is an important cause of MDS. We report the results of a clinical and genetic study of 20 patients from 11 families. We disclosed six novel and two previously described mutations in nine families. The majority of patients had a phenotype of myoclonus and dystonia in combination, but clinical findings considered atypical, such a very early onset, distal myoclonus, and legs involvement, were detected in a significant proportion of cases. The disease course was variable, from progression to spontaneous remission of the motor symptoms. There were no obvious differences between mutation-positive and -negative cases. PMID- 17853491 TI - Interface membrane fibroblasts around aseptically loosened endoprostheses express MMP-13. AB - The objective of this article was to assess whether matrix metalloproteinase-13 (MMP-13) is produced by cells of the peri-implant interface tissues and to further characterize these cells. Tissue specimens were collected from the bone prosthesis interface at the time of revision surgery of clinically loosened hip and knee arthroplasties (n = 27). Synovial tissues from osteoarthritic patients and young patients with mild joint deformity were used as controls (n = 6). Tissue samples were fixed in 4% PFA, decalcified with EDTA, and embedded in paraffin. Sections (4 microm) were stained with hematoxylin/eosin and for the osteoclastic marker enzyme tartrate resistant acid phosphatase. Monocytes/macrophages were characterized with a monoclonal antibody against CD68 and mRNAs encoding MMP-13 and alpha(1) collagen I (COL1A1) were detected by in situ hybridization. Cells expressing transcripts encoding MMP-13 were found in 70% of the interface tissues. These cells colocalized with a cell population expressing COL1A1 mRNA, and were fibroblastic in appearance. MMP-13 expressing cells were found in the close vicinity of osteoclasts and multinuclear giant cells. No signals for transcripts encoding MMP-13 were detected in multinuclear giant cells or in osteoclasts. Control tissues were negative for transcripts encoding MMP-13 mRNA. Fibroblasts of the interface from aseptically loosened endoprostheses selectively express MMP-13. By the expression and the release of MMP-13, these fibroblastic cells may contribute to the local degradation of the extracellular matrix and to bone resorption. PMID- 17853492 TI - Clonal T-cell response against autologous pleomorphic malignant fibrous histiocytoma antigen presented by retrieved HLA-A*0206. AB - Towards the goal of identifying tumor-rejection antigens on eradicated tumors in bone and soft tissue sarcomas, we evaluated the immune response against antigens presented by lost HLA class I molecules. Tumor specimens and peripheral blood samples were obtained from a 70-year-old woman with pleomorphic malignant fibrous histiocytoma. Over 1-year culture, a tumor cell line (MFH2004) was established. A B-cell line infected with Epstein-Barr virus (B2004-EBV) was developed from the blood samples. HLA genotypes of B2004-EBVcells were A*0206/2402, B*4006/4601, and C*0102/0801, whereas MFH2004 cells were defective for A*0206, B*4006, and C*0102. Loss of HLA-A2 expression was also proved immunohistochemically in the primary tumor tissues. Lost HLA-A2 in MFH2004 cells was retrieved by transfection of HLA A*0206 cDNA to develop MFH2004-A2. Attempts to induce CTLs by mixed culture with autologous T cells and MFH2004 cells resulted in failure. In contrast, those with MFH2004-A2 induced CTL clones CTL2004-c6 and CTL2004-c17. These CTL clones specifically killed MFH2004-A2 but not MFH2004 or B2004-EBV in an HLA-A2 restricted manner. These findings suggest that CTL2004-c6 and CTL2004-c17 recognize autologous tumor-rejection antigens presented by HLA-A*0206, which may have been expressed by tumor cells that had been eradicated by the host's immunosurveillance system. PMID- 17853493 TI - An instructive example of a long-latency adverse drug reaction--sclerosing peritonitis due to practolol. AB - OBJECTIVE: By examination of the original Yellow Card data to determine the duration of the latent period of the sclerosing peritonitis which formed part of the oculomucocutaneous syndrome that was associated with practolol, the beta adrenergic receptor blocking agent that was withdrawn from clinical usage in the UK in December 1975 in response to reports of the syndrome. METHOD: Relevant drug analysis prints (DAPs) for practolol were obtained from the Medicines and Healthcare Products Regulatory Agency (MHRA) and, by application to the Interim Committee on Yellow Card data, copies were obtained of the anonymised Yellow Card reports for all the 201 cases of sclerosing peritonitis that were reported in patients treated with practolol. These data were used to determine the latent period of this iatrogenic adverse drug reaction. RESULTS: It was shown that no other cause than practolol operated in all or a majority of the cases of sclerosing peritonitis and the suspected adverse reaction could properly be attributed to the drug. The latent period (the time period between the drug start date and the reaction start date) of the sclerosing peritonitis associated with practolol averaged 201 weeks (range 26-606 weeks; standard deviation 130 weeks). CONCLUSION: The latent period of the sclerosing peritonitis that formed part of the practolol oculomucocutaneous syndrome averaged about 4 years and had a range of from 0.5 to over 11.5 years. The Yellow Card Scheme could detect this ultra long-latency adverse reaction. PMID- 17853494 TI - "Hairy" single-walled carbon nanotubes prepared by atom transfer radical polymerization. AB - "Hairy nano-objects" are hybrid nanostructures comprising a core surrounded by a "hairlike" corona of flexible polymer chains, the role of which is typically to improve the solubility of the core material or to improve its dispersability and adhesion in other polymer matrices. Both aspects could be particularly useful with carbon nanotubes, especially in their applications as reinforcing agents. The controlled synthesis of hairy carbon nanotubes is accomplished by chemical modification with 2-bromopropionate followed by extension with poly(n-butyl acrylate) through atom transfer radical polymerization. The obtained hairy nanotubes are visualized at nearly molecular resolution with tapping-mode atomic force microscopy, providing insight into the uniformity of grafted chain lengths and grafting density. The grafting densities vary from approximately 1.0-10.0 chains nm(-1) along the nanotubes. Such a wide range of grafting density may indicate some chemical heterogeneity along and between the nanotubes; it may be also an indication of the challenges associated with carrying out chemical modification of nano-objects having high tendency to aggregate. PMID- 17853495 TI - Synthesis of magnetic microspheres with controllable structure via polymerization triggered self-positioning of nanocrystals. AB - A facile and novel method for the synthesis of magnetite-polymer hybrid microspheres with controllable structure is reported. On the basis of the interactions between polymers and magnetic nanocrytals, which are coated with a primary oleic acid layer, a variety of magnetic microspheres with well-tailored structure are fabricated by carefully modulating polymerization and selecting components of composite microspheres; the evolvement of hierarchical structure, and the magnetic properties of microspheres were systematically studied. Importantly, the mechanism of polymerization-triggered self-positioning of magnetic nanocrystals is investigated. PMID- 17853496 TI - Using magnetic force to enhance immune response to DNA vaccine. PMID- 17853497 TI - In situ Raman spectroelectrochemical study of 13C-labeled fullerene peapods and carbon nanotubes. AB - C60 fullerene peapods and double-walled carbon nanotubes (DWCNTs) containing highly 13C enriched C60 and inner tubes, respectively, are studied using Raman spectroscopy and in situ Raman spectroelectrochemistry in order to follow the influence of 13C enrichment on the vibrational pattern of these carbon nanostructures. The Raman response of 13C60 after encapsulation in fullerene peapods differs from that of isotope-natural species, (Nat)C60. The Raman A(g)(2) mode of encapsulated 13C60 is upshifted in frequency compared to that of the (Nat)C60 peapods with the same filling factor. The chemical doping of 13C60 peapods (peapod = C(60)@SWCNT) with K-vapor leads to the downshift of the A(g)(2) mode, similar to the case of (Nat)C60 peapods. The 13C60 peapods were successfully transformed into DWCNTs, which confirms high filling of single walled (SW) CNTs with 13C60. The DWCNTs exhibited distinctly downshifted G and D Raman modes for inner tubes, which proves that only inner tubes were enriched by 13C. The in situ Raman spectroelectrochemistry of (Nat)C60 exhibits strong anodic enhancement, while for 13C60 peapods the enhancement is only weak. On the other hand, the electrochemical charging of the inner-tube-labeled DWCNTs (13C(i) DWCNTs) followed the behavior of ordinary (Nat)C(i)-DWCNTs as indicated by in situ Raman spectroelectrochemistry. In addition, the spectroelectrochemical behavior of the G mode of inner tubes in 13C(i)-DWCNTs is followed from the start of the electrochemical doping, which was not feasible for (Nat)C(i)-DWCNTs. PMID- 17853498 TI - Morphology control of structured polymer brushes. AB - The surface-initiated photopolymerization (SIPP) of vinyl monomers on structured self-assembled monolayers, as defined by two-dimensional (2D) initiator templates for polymer growth, is investigated. The 2D templates are prepared by electron beam chemical lithography (EBCL) of 4'-nitro-4-mercaptobiphenyl (NBT) and chemical conversion to an asymmetric azo initiator (4'-azomethylmalonodinitrile 1,1'-biphenyl-4-thiol). Ex situ kinetic studies of the SIPP process reveal a linear increase in the thickness of the polymer layer with the irradiation/polymerization time. The effect of the applied electron dosage during the EBCL process upon the final thickness of the polymer layer is also studied. The correlation between the electron-induced conversion of the 4'-nitro to the 4' amino group and the layer thickness of the resulting polymer brush indicates that the polymer-brush grafting density can be directly controlled by the EBCL process. NBT-based template arrays are used for the combinatorial study of the influence of the lateral structure size and the irradiation dosage on the morphology of the resulting polymer-brush layer. Analysis of the array topography reveals the dependence of the thickness of the dry polymer layer on both electron dosage and structure size. This unique combination of EBCL as a lithographic technique to locally manipulate the surface chemistry and SIPP to amplify the created differences allows the preparation of defined polymer-brush layers of controlled morphologies. PMID- 17853499 TI - Charge-transport behavior in shape-controlled poly(3,4-ethylenedioxythiophene) nanomaterials: intrinsic and extrinsic factors. AB - The charge-transport behavior in one-dimensional (1D) poly (3,4 ethylenedioxythiophene) (PEDOT) nanomaterials of three different shapes is described. Both intrinsic and extrinsic factors are considered from the viewpoint of a single nanoparticle and nanoparticle assembly. Intrinsically, the oxidation level of the 1D PEDOT nanomaterials becomes higher with increasing aspect ratio of the nanomaterials, which is closely linked to the conjugation length. This result implies that the transport properties of the nanomaterials are significantly dependent on their shape. Extrinsically, the 1D PEDOT nanomaterials make an ohmic contact with gold interdigitated microelectrodes. In addition, a strong correlation is observed between the interparticle contact resistance and the shape of the nanomaterials. Lastly, the intrinsic and extrinsic factors related to charge transport are further illustrated by the resistance changes of nanomaterial-based chemical sensors. As a result, judicious tailoring of the dimensional and geometrical characteristics of the conducting-polymer nanomaterials may enable precise control over their transport properties as well as the characteristics of the nanomaterial-based devices. PMID- 17853500 TI - Mold and metallization: nanocontact molding for the fabrication of metal structures. PMID- 17853501 TI - 1,4-diazepine-2,5-dione ring formation during solid phase synthesis of peptides containing aspartic acid beta-benzyl ester. AB - The Fmoc-based SPPS of H-Xaa-Asp(OBzl)-Yaa-Gly-NH(2) sequences results in side reactions yielding not only aspartimide peptides and piperidide derivatives, but also 1,4-diazepine-2,5-dione-peptides. Evidence is presented to show that the 1,4 diazepine-2,5-dione derivative is formed from the aspartimide peptide. The rate of this ring transformation depends primarily on the tendency to aspartimide and piperidide formation, which is influenced by the nature of the amino acid following the aspartic acid beta-benzyl ester (Xaa). However the bulkiness of the amino acid side chain preceeding the aspartic acid beta-benzyl ester (Yaa) is also important. Under certain conditions the 1,4-diazepine-2,5-dione peptide derivative may even be formed dominantly, which is a highly undesirable side reaction in peptide synthesis, but which provides a new way for the synthesis of diazepine peptide derivatives with targeted biological or pharmacological activity. PMID- 17853502 TI - Viral peptide immunogens: current challenges and opportunities. AB - Synthetic peptide vaccines have potential to control viral infections. Successful experimental models using this approach include the protection of mice against the lethal Sendai virus infection by MHC class I binding CTL peptide epitope. The main benefit of vaccination with peptide epitopes is the ability to minimize the amount and complexity of a well-defined antigen. An appropriate peptide immunogen would also decrease the chance of stimulating a response against self-antigens, thereby providing a safer vaccine by avoiding autoimmunity. In general, the peptide vaccine strategy needs to dissect the specificity of antigen processing, the presence of B-and T-cell epitopes and the MHC restriction of the T-cell responses. This article briefly reviews the implications in the design of peptide vaccines and discusses the various approaches that are applied to improve their immunogenicity. PMID- 17853503 TI - Synthesis of cyclooctapeptides: constraints analogues of the peptidic neurotoxin, omega-agatoxine IVB-an experimental point of view. AB - omega-AGA IVB is an important lead structure when considering the design of effectors of glutamate release inducting P/Q-type calcium channels. The best route to achieve the analogues possessing the three-dimensional arrangement corresponding to the native binding loop was the introduction of constraint by ring formation via side chain to side chain lactamization for suitably protected Lys and Glu residues. Since tryptophane residue located at position 14 of this neuropeptide has been suggested as essential for binding, analogues in which this amino acid was replaced by aza-tryptophane and alanine were synthesized. The synthesis was carried out on various acid-labile resins (BARLOS chlorotrityl, Rink amide, PEG-based or Wang resins), by Fmoc strategy. In this paper, we describe optimization of the peptide cyclization with various protecting groups, and on resin or in solution cyclization experimental parameters. PMID- 17853504 TI - Complete assignments of (1)H and (13)C NMR spectroscopic data for two new triterpenoid saponins from Ilex pernyi. AB - Ilexpernoside A and ilexpernoside B, two new pentacyclic C(4)-nortriterpenoid saponins, were isolated from the leaves of Ilex pernyi Franch. Their chemical structures were determined by MS, NMR spectroscopy and chemical analysis. Complete assignments of the (1)H and (13)C NMR spectroscopic data were achieved by 1D and 2D NMR experiments (HSQC, HMBC, (1)H-(1)H COSY and NOESY). PMID- 17853505 TI - Drug price reform in the UK: debunking the myths. AB - The OFT report into the Pharmaceutical Price Regulation Scheme (PPRS) called for reform of the scheme, replacing existing profit and price controls with a system of value-based pricing (VBP). The report argued that VBP would be much more effective than the current PPRS both at providing value for money for the NHS and giving pharmaceutical companies the right incentives to invest in drugs in the future. The report has sparked a widespread debate about drug pricing in the UK and has been controversial in some quarters. Some of the more negative responses are, however, based on fundamental misconceptions about the OFT recommendations. In particular, contrary to some claims, the recommended system would provide strong incentives for incremental innovation and the right balance of rewards for first in class and follow-on products. Nor, as is sometimes argued, would VBP have an adverse effect on investment in the UK.Certainly, real challenges lie ahead if VBP is to be implemented. These concern the definition of value, particularly where patient benefits differ significantly by subgroup or indication, and the level of resource required to implement VBP. The OFT report contains proposals for addressing each of these areas. Perhaps the most difficult challenge is the political one: securing acceptance for a reform package that would create winners and losers among pharmaceutical companies according to their success in producing valuable drugs. Ultimately, however, only a scheme that does precisely this can hope to meet the needs of patients, the NHS and innovative companies in the long run. PMID- 17853506 TI - Cost inefficiency and hospital health outcomes. AB - This study explores the association between cost inefficiency and health outcomes in a national sample of acute-care hospitals in the US over the period 1999-2001, with health outcomes being measured by both mortality and complications rates. The empirical analysis examines health outcomes as a function of cost inefficiency and other determinants of outcomes, using stochastic frontier analysis to obtain hospital cost inefficiency scores. The results showed no systematic pattern of association between cost inefficiency and hospital health outcomes; the basic results were unchanged regardless of whether cost inefficiency was measured with or without using instrumental variables. The analysis also indicated, however, that the association between cost inefficiency and health outcomes may vary substantially across geographical regions. The study highlights the importance of distinguishing between 'good' costs that reflect the efficient use of resources and 'bad' costs that stem from waste and other forms of inefficiency. In particular, the study's results suggest that hospital programs focused on reducing cost inefficiency are unlikely to be associated with worsened hospital-level mortality or complications rates, while, on the other hand, across-the-board reductions in cost could well have adverse consequences on health outcomes by reducing efficient as well as inefficient costs. PMID- 17853507 TI - A simple primary care information system featuring feedback to clinicians. AB - A simple information system for primary care clinics was designed to support the USAID funded health system strengthening project in the Suez Governorate in Egypt. This system (FACT-Feedback and Analytic Comparison Tool) was implemented in December 2003 in 14 primary care clinics. The MS Access-based system was designed and prototyped in several months, and was easily and cheaply modified several times after implementation. A total of 128 562 persons have been registered in the system (as of June 2005) and 36 083 visits have been documented. A key feature of FACT is the ease with which clinicians can conduct exploratory research about practice patterns, and variations in them across doctors and the other clinics. This analytic feature enables the clinicians to self-diagnose quality problems and take action accordingly. Several of the clinics have used this feature of FACT to identify important gaps in service use among patients, and have taken steps to remove barriers to promote more appropriate patterns of utilization. The paper reviews the design and implementation issues and early evidence of the system's utility in helping support quality improvement (QI) work in the clinics. PMID- 17853508 TI - Changing trends in the decision-making preferences of women with early breast cancer. AB - BACKGROUND: Previous studies have indicated a predominance of passive decision making styles among women with early-stage breast cancer in the UK offered a choice between breast-conserving surgery (BCS) and mastectomy. The aim of this study was to determine current decision-making styles and establish their association with operation choice and breast unit mastectomy rate. METHODS: A questionnaire survey was conducted among women from three specialist breast units representing high, medium and low case mix-adjusted mastectomy rates. RESULTS: Of 697 consecutive patients, 356 (51.1 per cent) completed the questionnaire, a mean of 6.9 (range 1.3-48.6) weeks after surgery. Some 262 women (73.6 per cent) underwent BCS and 94 (26.4 per cent) had a mastectomy. Some 218 patients (61.2 per cent) achieved their preferred decision-making style. The proportions of women achieving an active decision-making style were high, particularly for those choosing mastectomy (83 versus 58.0 per cent for BCS; P < 0.001) and in the high mastectomy rate unit (79.6 versus 53 and 52.2 per cent for medium and low rate units respectively; P < 0.001). CONCLUSION: More women chose an active decision making style than in previous UK studies. The provision of greater treatment selection autonomy to women suitable for BCS may not reduce mastectomy rates. PMID- 17853509 TI - Computed tomography evaluation of regional lymph node metastases in patients with biliary cancer. AB - BACKGROUND: Identification of lymph node metastases in biliary cancer is important for determining prognosis and surgical planning, but the effectiveness of computed tomography (CT) in diagnosing node metastases of the hepatoduodenal ligament (peribiliary and retroportal nodes) or around the common hepatic artery is unknown. METHODS: CT scans and pathological results from 146 patients who had undergone regional lymphadenectomy for biliary carcinoma were reviewed. To evaluate the regional lymph nodes, long- and short-axis diameters of lymph nodes were measured and axial ratios calculated (short-axis diameter/long-axis diameter). Nodes were considered round if the axial ratio exceeded 0.7. Internal lymph node structures were also evaluated. RESULTS: The presence of a round node with a short-axis diameter exceeding 16 mm had a positive predictive value (PPV) of 56 per cent for the presence of metastatic foci, and node heterogeneity had a PPV of 64 per cent. The highest PPV (67 per cent) was obtained for round nodes greater than 18 mm in short-axis diameter, but nodes of this size and character were rare. CONCLUSION: CT is not useful for predicting regional lymph nodal metastases in biliary carcinoma. PMID- 17853510 TI - A rapid CZE method for the analysis of benzodiazepines in spiked beverages. AB - A rapid CZE method was developed for the simultaneous determination of nine benzodiazepines in spiked beverages (nitrazepam oxazepam, alprazolam, flunitrazepam, temazepam, diazepam, 7-aminoflunitrazepam, 7-aminonitrazepam and 7 aminoclonazepam). The method employed a double-coated capillary coated with poly(diallyldimethylammonium chloride) and then dextran sulphate. The BGE conditions were 100 mM ammonium phosphate buffer, pH 2.5, which gave baseline resolution between consecutive peaks and a run time of less than 6.5 min. This method offers improvements in both resolution and run time, compared to those attained under analogous conditions with an uncoated capillary. The validated method was successfully applied to beverages that had been spiked with benzodiazepines at concentrations simulating prescription tablets. No sample pretreatment was required to quantify five benzodiazepines in Coca-Cola, orange juice, beer, bourbon and Bacardi. The exception was white wine, where the complex sample matrix did not enable the accurate quantification of nitrazepam. PMID- 17853511 TI - A two-dimensional proteome reference map of Herbaspirillum seropedicae proteins. AB - Herbaspirillum seropedicae is an endophytic diazotroph associated with economically important crops such as rice, sugarcane, and wheat. Here, we present a 2-D reference map for H. seropedicae. Using MALDI-TOF-MS we identified 205 spots representing 173 different proteins with a calculated average of 1.18 proteins/gene. Seventeen hypothetical or conserved hypothetical ORFs were shown to code for true gene products. These data will support the genome annotation process and provide a basis on which to undertake comparative proteomic studies. PMID- 17853512 TI - Differential protein expression in male and female human lumbar cerebrospinal fluid using iTRAQ reagents after abundant protein depletion. AB - Cerebrospinal fluid (CSF) has become one of the most frequently used biological medium for physiological studies for neurological disorders due to its proximity to the brain and clinical availability; however, before undertaking a rational approach to biomarker discovery or diagnostics, it is crucial to understand the underlying characteristics of CSF proteome in subpopulations. In this study, we examined the differential expression of proteins in pooled male and female CSF utilizing isobaric tags for relative and absolute quantification (iTRAQ) reagents after the depletion of six high abundant proteins using a multiple affinity removal system (MARS). A total of 219 proteins were identified (95% confidence level), and 12 proteins showed difference in expression levels. Eleven out of 12 differentially expressed proteins showed ratios of male/female between 1.15 and 1.29 (duplicate average), indicating a remarkable similarity between male and female CSF. One notable exception was the slightly lower expression level of ceruloplasmin (ferroxidase) in male CSF (0.81), a copper containing protein that catalyzes the conversion of ferrous iron to ferric iron with antioxidant properties. We also examined the levels of ceruloplasmin in each individual patient sample which constituted the pooled CSF using Western blot analysis which confirmed the lower expression levels of ceruloplasmin in male CSF. PMID- 17853513 TI - A novel late embryogenesis abundant protein and peroxidase associated with black point in barley grains. AB - Black point of barley grain is a disorder characterised by a brown-black discolouration at the embryo end of the grain. Black point is undesirable to the malting industry and results in significant economic loss annually. To identify proteins associated with barley black point we utilised a proteomic approach with 2-DE to compare proteins from whole grain samples of black pointed and healthy grain. From this comparison two condition-specific proteins were identified: a novel 75 kDa late embryogenesis abundant (LEA) protein and a barley grain peroxidase 1 (BP1) that were specifically more abundant in healthy grain and black pointed grain, respectively. Although LEA protein was less abundant in black pointed grain, LEA gene expression was greater suggesting protein degradation had possibly occurred in black pointed grain. Similarly, the increase in BP1 in black pointed grain could not be explained by gene expression. Western blot analysis also revealed that the identified LEA protein is biotinylated in vivo. The role that each of these proteins might have in black point development is discussed. PMID- 17853514 TI - On-plate digestion of proteins using novel trypsin-immobilized magnetic nanospheres for MALDI-TOF-MS analysis. AB - In this study, a novel method of on-plate digestion using trypsin-immobilized magnetic nanospheres was developed followed by MALDI-TOF-MS for rapid and effective analysis and identification of proteins. We utilized a facile one-pot method for the direct preparation of amine-functionalized magnetic nanospheres with highly magnetic properties and the amino groups on the outer surface. Through the reaction of the aldehyde groups with amine groups, trypsin was simply and stably immobilized onto the magnetic nanospheres. The obtained trypsin-linked magnetic nanospheres were then applied for on-plate digestion of sample proteins (myoglobin and Cytochrome c). Moreover, after digestion, the trypsin-linked nanospheres could be easily removed from the plate due to their magnetic property, which would avoid causing contamination on the ion source chamber in MS. The effects of the temperature and incubation time on the digestion efficiency were characterized. Within only 5 min, proteins could be efficiently digested with the peptide sequence coverage higher than or equal to that of the traditional in-solution digestion for 12 h. Furthermore, RPLC fractions of rat liver extract were also successfully processed using this novel method. These results suggested that our improved on-plate digestion protocol for MALDI-MS may find further application in automated analysis of large sets of proteins. PMID- 17853516 TI - Synthesis and structure of novel sugar-substituted bipyridine complexes of rhenium and 99m-technetium. AB - Novel ligands have been obtained from the reaction of 4,4'-dibromomethyl-2,2' bipyridine with 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosylthiol, 2,3,4,6-tetra O-acetyl-beta-D-galactopyranosylthiol or 2,3,4,6-tetra-O-acetyl-alpha-D thioacetylmannopyranoside in which the sugar residues are thioglycosidically linked to the bipyridine in the 4,4'-position. Cleavage of the acetyl groups affords hydrophilic symmetric ligands with free hydroxyl groups. Reaction of the new glycoconjugated ligands (L) with [Re(CO)(5)Cl] yields fluorescent complexes of general formula [Re(L)(CO)(3)Cl], which were characterised by mass spectrometry, elemental analysis and (1)H and (13)C NMR, IR, UV/Vis and fluorescence spectroscopy. These complexes exhibit excellent solubility and stability in organic solvents or water, depending on the residues of the sugar. One complex, namely tricarbonyl-4,4'-bis[(2,3,4,6-tetra-O-acetyl-beta-D glycopyranosyl)thiomethyl]-2,2'-bipyridinerheniumtricarbonylo chloride, has been characterised by X-ray crystallography. A non-symmetric structure of the complexes could be assigned. Radiolabelling of the unprotected ligands with [(99m)Tc(H(2)O)(3)(CO)(3)](+) affords the corresponding water-soluble technetium complexes (in quantitative yields), which were characterised by their HPLC radiation traces. The formed complexes are stable for several hours in the presence of histidine but show partial ligand-exchange after one day. PMID- 17853515 TI - DNA binding by a new metallointercalator that contains a proflavine group bearing a hanging chelating unit. AB - The new bifunctional molecule 3,6-diamine-9-[6,6-bis(2-aminoethyl)-1,6 diaminohexyl]acridine (D), which is characterised by both an aromatic moiety and a separate metal-complexing polyamine centre, has been synthesised. The characteristics of D and its ZnII complex ([ZnD]) (protonation and metal complexing constants, optical properties and self-aggregation phenomena) have been analysed by means of NMR spectroscopy, potentiometric, spectrophotometric and spectrofluorimetric techniques. The equilibria and kinetics of the binding process of D and [ZnD] to calf thymus DNA have been investigated at I=0.11 M (NaCl) and 298.1 K by using spectroscopic methods and the stopped-flow technique. Static measurements show biphasic behaviour for both D-DNA and [ZnD]-DNA systems; this reveals the occurrence of two different binding processes depending on the polymer-to-dye molar ratio (P/D). The binding mode that occurs at low P/D values is interpreted in terms of external binding with a notable contribution from the polyamine residue. The binding mode at high P/D values corresponds to intercalation of the proflavine residue. Stopped-flow, circular dichroism and supercoiled-DNA unwinding experiments corroborate the proposed mechanism. Molecular-modelling studies support the intercalative process and evidence the influence of NH+...O interactions between the protonated acridine nitrogen atom and the oxygen atoms of the polyanion; these interactions play a key role in determining the conformation of DNA adducts. PMID- 17853517 TI - Structures with tunable strong ferromagnetic coupling: from unordered (1D) to ordered (Discrete). AB - The X-ray crystal structures, magnetic susceptibilities from 2 to 300 K, and theoretical analyses of the magnetism for 1D and trinuclear azido Cu(II) carboxylate complexes [Cu(1.5)(hnta)(N(3))(2)(H(2)O)](n) (1) and [Cu(3)(hnta)(4)(N(3))(2)(H(2)O)(3)] (2), respectively, where hnta is 6 hydroxynicotinate, are described. Although both exhibit strong ferromagnetic coupling, discrete complex 2 exhibits long-range ferromagnetic ordering, while the very similar 1D system 1 does not. Density functional calculations provided accurate J values and allowed rationalization of the ferromagnetic coupling in terms of the magnetic orbitals and spin densities. PMID- 17853518 TI - The isolation of basic proteins by solid-phase extraction with multiwalled carbon nanotubes. AB - Multiwalled carbon nanotubes (MWCNTs) have been employed for the first time as sorbents for the isolation of basic proteins from other protein species in biological sample matrices by solid-phase extraction (SPE). A microcolumn packed with MWCNTs was incorporated after appropriate pretreatment into a sequential injection system, which facilitates online selective sorption of basic protein species (hemoglobin and cytochrome c in this particular case). The retained protein species were afterwards separated from each other by sequential elution from the microcolumn through the employment of appropriate eluents. A 0.025 mol L(-1) phosphate buffer solution of pH 8.0 facilitated the efficient collection of hemoglobin, while a 0.5 mol L(-1) NaCl solution ensured the quantitative recovery of the retained cytochrome c. With a sample loading volume of 2.0 mL, enrichment factors of 11 and 15 were derived for hemoglobin and cytochrome c, along with retention efficiencies of 100% for both species and recovery rates of 98 and 90%, respectively. A sampling frequency of 8 h(-1) was achieved, and the precisions were 3.0% and 0.8% (RSD) for hemoglobin and cytochrome c at a concentration of 5.0 microg mL(-1). The practical applicability of this system was demonstrated by processing of human whole blood for isolation of hemoglobin, and satisfactory results were obtained by assay with SDS-PAGE. PMID- 17853519 TI - Synthesis and biological studies of inducible DNA cross-linking agents. PMID- 17853520 TI - Probing local structural events in beta-hairpin unfolding with transient nonlinear infrared spectroscopy. PMID- 17853521 TI - A platinum-free zero-carbon-emission easy fuelling direct hydrazine fuel cell for vehicles. PMID- 17853522 TI - The reaction mechanism of p-toluenediamine anodic oxidation: an in situ ESR UV/Vis/NIR spectroelectrochemical study. AB - In situ ESR-UV/Vis spectroelectrochemistry is applied to obtain new insights into the intermediates and reaction products of the anodic oxidation of p toluenediamine in aqueous solution at different pH values. A strong pH dependence of the stability of the cation radical is found. While the absence of a stable radical was proved by ESR spectroscopy at pH 2 and 10, this radical is detected at medium pH values and assigned to the semiquinonediimine structure. The UV/Vis absorption of the radical is observed at these pH values as well. The p toluenediimine intermediate and the trimeric reaction product were followed during the electrode reaction by UV/Vis spectroscopy at all pH values. PMID- 17853523 TI - First kinetic determination of partition coefficients for organic compounds between the three microenvironments of AOT-based microemulsions. AB - Kinetic data for the hydrolysis of N-picolinoylimidazole (I) and 2,4 dinitrophenylpicolinate (II) in AOT [bis(2-ethylhexyl) sodium sulfosuccinate] microemulsions are used to determine for the first time the two partition constants for each substrate (i.e. K(wi) and K(oi), corresponding to the incorporation of substrate molecules from water microdroplets and the continuous medium, respectively, into the interface). Application of the pseudophase formalism to the partition constants allowed the rate constant in each phase to be determined. The rate of hydrolysis of II increased with decreasing polarity of the medium; as a result, the hydrolysis reaction took place largely at the interface. On the other hand, the rate of hydrolysis of acylimidazole I decreased with decreasing polarity, possibly as a result of changes in the resonance structures of the reagent causing the hydrolysis process to occur preferentially in water microdroplets. PMID- 17853524 TI - Hierarchical organisation on a two-dimensional supramolecular network. PMID- 17853525 TI - End-of-life and palliative care issues in medical and nursing schools in the United States. AB - Medical and nursing schools in the United States have traditionally had a limited emphasis on end-of-life care. The present study is a comparison of these 2 professional programs' current offerings on death education. Data were gathered via a mailed survey from the 122 medical schools in 2005 and the 580 baccalaureate nursing programs in 2006. Return rates of 81% and 71%, respectively, were received. All medical schools and 99% of nursing schools reported offering something on death and dying, with over 90 % of students in these programs participating. The average number of hours offered in both professional programs is less than 15. Over 87% in both programs have offerings in palliative care. Whereas nursing programs rely almost solely on nurses for end of-life course provisions, medical schools are more interdisciplinary by faculty. End-of-life issues are presented in both medical and nursing curricula, though on a limited basis. This emphasis exposes students to the issues, though not in an in-depth way. PMID- 17853526 TI - Psychological defenses against death anxiety: integrating Terror Management Theory and Firestone's Separation Theory. AB - The author attempts to integrate Terror Management Theory (TMT) and R. W. Firestone's Separation Theory (1984, 1994). Both theories emphasize defense against death anxiety as a key human motive. Whereas TMT focuses extensively on self-esteem and cultural worldview, Firestone posited additional defenses such as gene survival, self-nourishing behaviors, addictive couple bonds, and adopting an anti-sexual approach to life. TMT offers a strong base of experimentally validated ideas and the experimental paradigms to test the broad array of defenses enumerated in Firestone's Separation Theory. Therefore, an integration of the two theories would be beneficial to a fuller understanding of psychological defenses against death anxiety. PMID- 17853527 TI - Risk-taking and reasons for living in non-clinical Italian university students. AB - The associations between risk-taking, hopelessness, and reasons for living were explored in a sample of 312 Italian students. Respondents completed the Physical Risk Assessment Inventory, the Physical Risk-Taking Behavior Inventory, the Beck Hopelessness Scale, and the Reasons for Living Inventory. Students with lower scores on the Reasons for Living Inventory and higher scores on the Beck Hopelessness Scale rated the risky activities as less risky and engaged in them more often. Women obtained higher scores on risk assessment, lower scores on personal risk-taking and higher scores on the Reasons for Living Inventory and most of its subscales. Men in general and people who take risks and perceive lower risk are more hopeless and relatively weak in reasons for living. PMID- 17853528 TI - Age, gender, and living circumstances: discriminating older adults on death anxiety. AB - The present study examines the effect of age, gender, and living circumstances on elderly persons' death anxiety. For this purpose, 299 persons attending public parks (average age = 70 years) were interviewed using the Death Anxiety Survey Schedule, which is a set of 10 questions related to death anxiety from an Indian perspective. Women, those relatively older, and those living with family were significantly more anxious about the word death. The gender and age results in this Indian sample are similar to that in some western samples. The results that those living with family have significantly higher death anxiety are not in agreement with past western studies and may reflect cultural differences in anxiety about death. PMID- 17853530 TI - A new feature: our scientific heritage. PMID- 17853529 TI - Clinical predictors of urinary retention after pelvic reconstructive and stress urinary incontinence surgery. AB - OBJECTIVE: To evaluate the impact of perioperative variables on length of postoperative catheterization. STUDY DESIGN: A multicenter, prospective, cohort study of women undergoing pelvic reconstructive and/or incontinence surgery was performed. Perioperative variables associated with length of catheterization and prolonged catheterization (catheterization >30 days) were analyzed. Univariate logistic regression was used identify variables associated with urinary retention. Multivariate logistic regression analysis was performed on variables identified by univariate analysis to construct the best model predicting prolonged postoperative catheterization. RESULTS: Catheterization data were available for 408 patients. Mean catheterization length was 11 +11 days. Thirty four patients required prolonged catheterization. Logistic regression analysis selected 3 variables as predictors of prolonged catheterization: performance of pubovaginal sling (OR 5.44), performance of vaginal apex suspension (OR 2.32) and preoperative presence of grade 3/4 vaginal apex descent (OR 2.75) (all p < or =0.05). The probability of prolonged catheterization occurring in the absence of any of the predictors was 2% and increased to 5-11% if 1 predictor was present. When all 3 were present, the probability of prolonged catheter use increased to 45%. CONCLUSION: The performance of a pubovaginal sling and of a vaginal apex suspension or the preoperative presence of grade 3/4 vaginal apex descent are associated with prolonged postoperative catheterization. PMID- 17853531 TI - [The reform of the health care system for the elderly in Japan]. PMID- 17853532 TI - [A systematic review of randomized controlled trials of exercise and lifestyle intervention for the health promotion of older adults--issues and an effective model of intervention]. PMID- 17853533 TI - [Clinical aspect and mycology of dermatophytosis--the first step in identifying dermatophytes]. PMID- 17853534 TI - [Clinical aspect of dermal candidiasis]. PMID- 17853535 TI - [Pathogenesis of Parkinson disease]. AB - Although the pathogenesis of Parkinson disease (PD) is still unclear, various studies have uncovered important clues to the cause of the dopaminergic cell death. Accumulating evidence has suggested that both environmental and genetic factors collaborate and cause dopaminergic cell death. Aging, exposure to pesticides, and endogenous toxic agents, such as dopamine derivatives, mighty induce oxidative stress and lead to neurodegeneration. The studies on familial PD related genes indicate that impairment of the ubiquitin-proteasome system induces the accumulation of misfolded protein, mainly alpha-synuclein, leading to cell death. This review discusses the possible mechanisms, underlying sporadic and familial PD. PMID- 17853536 TI - [Mycological study of Candida]. PMID- 17853537 TI - [Molecular biological methods for dermatomycosis]. PMID- 17853538 TI - [Simple mycological methods]. PMID- 17853539 TI - Stats snapshot ... encouraging physicians to adopt information technology to participate in pay-for-performance programs. PMID- 17853540 TI - Use of covariates in randomized controlled trials. PMID- 17853541 TI - [Complex treatment of patients with burn cicatricial deformity of mammary gland with TRAM-flap transplantation and NO-therapy]. PMID- 17853542 TI - [Surgical treatment of iatrogenic thrombosis of femoral vein after hernioplasty]. PMID- 17853543 TI - [Puncture treatment of pancreatic pseudocysts]. PMID- 17853544 TI - [Current tendencies in surgical treatment of patients with postoperative and recurrent ventral hernias]. PMID- 17853545 TI - [Study of osteoinductive and osteoconductive properties of new resorbable membrane for bone tissue directed regeneration in in vivo experiments]. PMID- 17853546 TI - [Computer forecasting of the efficacy of intracrown chemical whitening of teeth]. PMID- 17853547 TI - [Technique of occlusal contacts surface determination with the use of Adobe Photoshop and Universal Desktop Ruler]. PMID- 17853548 TI - [About self-regulation potential of dentomaxillary anomalies and deformations in children with disturbance of musculoskeletal apparatus]. PMID- 17853549 TI - [Nitrite test in Pseudomonas aeruginosa urinary tract infections]. AB - Pseudomonas aeruginosa (PA) is considered to be bacteria with a low capability to produce nitrite. OBJECTIVE: To investigate the incidence of a positive urine nitrite test in community-acquired urinary tract infections (UTI) in children, caused by PA. METHODS: The medical records of 38 children (18 females) admitted for febrile PA UTI during a period of 7 years were reviewed. Urine nitrite tests were carried out using dipstrips, and results were reported as positive or negative. RESULTS: Of the 38 patients, 17 had a positive nitrite test and 21 had a negative test (proportion of positive 0.45, 95% confidence interval 0.29 to 0.61). Pyuria was detected in 13/17 patients with a positive nitrate test vs. 5/21 with a negative test (p=0.003). Data regarding renal ultrasound (US) were available for 35 patients, and in 20 abnormalities were detected, 14/17 in the positive vs. 6/18 in negative nitrite group (p = 0.001). CONCLUSION: The urine nitrite test may be positive in PA UTI, therefore, a positive test does not rule out Pseudomonas UTI. PMID- 17853550 TI - [Non-urgent compulsory hospitalization]. AB - The Israel Mental Health Law of 1991 gave authority to the regional psychiatrist to give orders of compulsory hospitalization - urgent and non-urgent. The non urgent Hospitalization Order applies to conditions of non-immediate danger, in which potential for significant damage or harm to the patient or others is expected. Authority is granted to the District Psychiatric Committee as a body of appeal (before the Hospitalization Order is carried out) and as a tribunal to decide upon continuation after the first two weeks of hospitalization. This article aims to stress the main problems encountered by psychiatrists regarding management and treatment under the Non-Urgent Compulsory Hospitalization Order: 1) Postponing hospitalization or releasing a patient for 24 hours, in order to launch an appeal before receiving any treatment, may facilitate clinical deterioration. The ambiguous waiting period could enhance anxiety, acting out and dangerousness. 2) The article discusses clinical and legal aspects of compulsory hospitalization - both urgent and non-urgent. The diverse problematic issues will be elaborated through three clinical cases, and, when clinically indicated, proposals raised for possible solutions in converting an urgent compulsory order to a non-urgent compulsory order. PMID- 17853551 TI - [Attitudes of immigrants from the former Soviet Union towards complementary medicine]. AB - BACKGROUND: The use of complementary and alternative medicine (CAM) in primary care in Israel is growing. Limited data is available on the influence of immigration and cross-cultural health-beliefs concerning CAM use. OBJECTIVES: This study explores the perspectives toward CAM of immigrants who came to Israel since 1990 from the former Soviet Union. RESEARCH DESIGN AND METHODS: Questionnaires were administered to a random sample of patients attending an urban academic primary care clinic located in Northern Israel. RESULTS: Out of 1146 participants in this study, 106 were immigrants from the former Soviet Union. No statistical significance was found in the extent of CAM use in the last year among immigrants (63%) and non-immigrants (54%). Immigrants using CAM reported significantly less in reference to CAM practitioners and more use of herbal products. They also more significantly supported the idea of including an herbal therapist in the clinical staff at the medical center. Both groups expected their family physician to refer them to CAM, but immigrants had significantly higher expectations of their physician to provide CAM. Both groups anticipated an active role for their family physician in a future scenario of integrative care at the clinic. CONCLUSIONS: The use of CAM in primary care can be interpreted in a cross-cultural perspective. Patients who emigrated from the former USSR have unique perspectives toward CAM. The authors propose practical suggestions for primary care clinicians concerning anamnesis of immigrants regarding CAM. They also suggest health administrators take into account cross cultural diversity when planning integration of CAM in primary care. PMID- 17853552 TI - [Frequency and reasons for falling among residents of the geriatric center]. AB - BACKGROUND: One of the serious problems in geriatrics is falling among the elderly population. It is noted that, as age progresses, the frequency of falling increases, reaching 1.4-4.5 falls per person annually among nursing home residents. Furthermore, recurrent falls are one of the main reasons for their residence in the geriatric nursing home. AIM: The purpose of the study was to determine the frequency and main causes of recurrent falls among mobile nursing home residents, to examine the influence of medications on the frequency of falls and to observe the influence of falls on changes in their health condition and mortality. PATIENTS AND METHODS: During the past 5 years, researchers tracked falls among 242 mobile residents at the "Gil-Ad" Geriatric Center, (mean age 85.2+/-1.2 years). Among observed patients 170 (70.2%) had fallen 959 times, (1.13 falls per person annually). This created a statistical image of the mobile resident, predisposed to recurrent falls: she is the elderly woman aged 83 years and older, suffering from pain, cardiovascular diseases (55.8%), touch infringements due to decreased visual acuity and hearing (76.4%), atrophic musculoskeletal diseases or after orthopedic operations (68.6%) and acute infections (51.2%). A direct link was found between the frequency of falls and the amount of medications provided to the elderly patients: for residents, predisposed to recurrent falls, treatment by 5 and more kinds of drugs, including diuretics, was characteristic. The study proves a mutual dependency between frequency of falls and the functional status of the elderly residents of the geriatric center. CONCLUSION: For prevention of falls and bone fractures among elderly nursing home residents, the clinicians should carefully assess their functional status, in view of diseases and drug treatment. PMID- 17853553 TI - [Sexual dysfunction, depression and quality of life in male implantable cardioverter defibrillator (ICD) recipients--with and without shock delivery]. AB - BACKGROUND AND OBJECTIVES: Sexual concerns are prevalent among ICD recipients. Our goal was to evaluate the prevalence of sexual dysfunction (SD), depression, and quality of life (QOL) in male recipients of ICD with and without shock delivery. PATIENTS AND METHODS: ICD implanted males were asked to fill-out 3 self administered questionnaires: Florida Patient Acceptance Survey (FPAS), Centre for Epidemiologic Studies Depression Scale (CES-D), and Arizona Sexual Experiences Scale (ASES). All patients were offered a referral to a sex clinic. RESULTS: A total of 47/72 patients (65%), agreed to participate. Patients were classified into no-shock [NS] (66%) and at least one shock [S] (34%) groups. SD defined as worse than median ASES male score was found in 42.6% of the patients, 52% and 25% in NS/S groups, respectively (p = 0.08). ICD related deterioration in sexual function (SF) was reported by 71% vs. 44% of NS/S groups, respectively (p = 0.069), and by 85% of the patients with SD vs. 44.4% of the better SF group (p = 0.005). Twenty three (49%) patients were referred to a sex clinic. Depression (CES-D score= 16) was found in 36% of the study group. CES-D score mean ranks were 21 vs. 30 in the NS/S groups respectively, (p = 0.049). QOL was similar in NS/S groups. No correlation was found between SD and depression or QOL, however, depression correlates with low QOL (Pearson correlation = 0.416, p = 0.04). CONCLUSIONS: ICD implantation seems to impair male SF. Receiving a shock might be associated with a protective effect on SF. ICD implanted males are at risk for depression S > NS. QOL was similar in NS/S groups. ICD implanted males should be screened and treated for SD and depression. PMID- 17853554 TI - [Parathyroid cyst associated with acute respiratory failure and jugular vein thrombosis]. AB - Parathyroid cysts are much less common than other cystic lesions of the neck. The great majority of parathyroid cysts are endocrine non-functioning. Parathyroid cysts may become symptomatic because of hormonal activity or due to the size and pressure effects. This is a case history of a 43 year-old woman, who presented with dyspnea. A 9 + 8 + 6cm cervical-mediastinal parathyroid cyst causing dyspnea, dysphagia, respiratory failure and jugular vein thrombosis was found. PMID- 17853555 TI - [Involuntary hospitalization and treatment: the interface between psychiatry and law]. AB - Involuntary or compulsory hospitalization and treatment of mentally ill patients is one of the most distressing societal needs. The decision to hospitalize or treat an individual involuntarily must balance between three ethical issues: the patient's right to receive medical care, the patient's personal rights to liberty and dignity, and the protection of the public. The psychiatrist is concerned with the need for medical treatment, while the courts follow the letter of the law in order to ensure protection of the individual's rights, as well as those of the public. The interaction between the psychiatric (or medical) discipline and the judicial discipline comprises inherent difficulties, due to these differences in focus of concern and due to the differences in the language they use. In the civil compulsory hospitalization, it is the definition and prediction of dangerousness that comprises a potential discourse and misunderstanding between the psychiatric and the judicial system. It seems that both systems, as well as the patients, may benefit if the initial decision to hospitalize involuntarily is taken by the medical representatives (the District Psychiatrist, Hospital Director, three physicians, etc.) as an emergency procedure. The decision to continue the involuntary hospitalization should be taken by a judicial representative (or a committee), based on the psychiatric evaluation, within 72 hours instead of the 14 days as is currently stated in the Mental Health Law. The less restrictive alternative to hospitalization, compulsory outpatient treatment, is still controversial. This is an order "with no bite" and its implementation is determined, in effect, by the patient's goodwill and cooperation. There are no legal or other consequences for patients who do not comply with the outpatient treatment order. This is true for both civil and criminal outpatient orders. Without legal sanctions this model of outpatient treatment is not really "compulsory" and does not achieve its preventive goals. PMID- 17853556 TI - [Diagnostic tests for urinary tract infection]. AB - The clinical suspicion for urinary tract infection usually begins with simple laboratory aid: the urinalysis, performed many times in a small laboratory by the physician himself. A well-performed urinalysis can still provide valuable information for many diseases, including urinary tract infection. However, physicians need to remain proficient in this procedure. This article reviews the basic steps, as well as potential pitfalls, for the proper performance of this old, but still relevant, medical skill. PMID- 17853557 TI - [Carrying out the compulsory orders in psychiatry]. AB - The way a modern society frames its Mental Health Act, especially the clauses pertaining to the compulsory management of those suffering from mental illness, reflects the manner in which it resolves the inherent conflict between the individual's right for personal liberty and dignity and the society's right for safety. The authors review legislation regarding compulsory examination and involuntary hospitalization of individuals suffering from mental illness, of 8 Western countries. The review focuses on both the criteria allowing such compulsory management and the rules that determine how these laws are enforced. In Israel, a Mental Health Act was first enacted in 1955 and then revised in 1991. Both Acts contain clauses establishing the necessary and sufficient conditions for compulsory examination or involuntary hospitalization of persons under emergency or non-emergency circumstances. By requiring more stringent criteria for involuntary confinement, compared with the early Act of 1955, the 1991 Act begins a trend of favoring the individual's rights. Later, as the review reveals, judges in Israel have continued this trend by requiring greater proof of dangerousness and by allowing more room for appeals. To examine issues pertaining to the mechanisms by which compulsory management of persons under the Mental Health Act is carried out, the authors present a retrospective survey on 170 cases of compulsory management, both compulsory examination and involuntary hospitalization, in a three month period in 2005. The results indicate that in 48.3% of cases the orders were carried out after one visit, 71.7% of the cases ended in involuntary hospitalization. Regarding the individuals' response to involuntary confinement, the findings indicate that 43% willfully complied while 7.2% vigorously or violently objected requiring the intervention of the police. PMID- 17853558 TI - [Outpatient commitment under court order in psychiatry]. AB - Outpatient commitment under court order is a controversial issue among mental health professionals in different countries. This kind of outpatient involuntary treatment is provided for mental patients suspected to have committed a crime endangering society while in a severe psychotic state. Despite their dangerousness, the Israeli Mental Health Law of 1991 provides outpatient commitment under court order as an alternative to inpatient commitment. This legal provision raises several concerns and important ethical questions. A major dilemma is the question of whether this legal tool is efficacious in stabilizing the mental condition of criminal mental patients in order to prevent the perpetuation of violent crimes in an open setting such as outpatient clinics. Other major concerns are: (a) who bears the responsibility for the implementation of the enforcement? (b) how the enforcement might be implemented? This paper discusses this complex issue and presents some possible solutions aimed at improving the practical use of this important component of the comprehensive modern system of care for mental patients. PMID- 17853559 TI - [The involuntary hospitalized psychiatric patient, present-but-missing]. AB - The Israeli Treatment of Mental Patient Law of 1991 reflects an innovative approach which promotes the use of compelled treatment order in the community as the least restrictive environment alternative for involuntary psychiatric hospitalization. This law grants the Regional Psychiatric Committees with authorities regarding the involuntary placement of such patients by court. The proportion of court order induced involuntary psychiatric hospitalizations among the total psychiatric hospitalizations is increasing with time. The 2004 Correction to the Act, clause 29a, states that a psychiatric patient may be represented in the Regional Psychiatric Committee by a legal advocate, and settles the options to materialize this right. The 2004 Correction is not yet applied in all regions in Israel. The Committees do not usually promote compelled treatment in outpatient clinics as a follow-up or an alternative for involuntary psychiatric hospitalizations. Involuntary hospitalizations by court order bear no time limits despite a former decision of the Israeli High Court of Justice. The lack of an obligatory legal representation for the psychiatric patient further ensures that the option of compelled treatment in outpatient clinics is not satisfactorily considered. In our opinion, the current reality of involuntary hospitalization orders that bear no time limits; the underuse of the compelled out patient clinic treatment option; and the lack of obligatory legal representation for the patients, results in an inappropriate application of the treatment policy of least restrictive environment. The patient is often regarded as present-but-missing. The awareness to patients' human rights in the Israeli psychiatric system must be emphasized, and suitable resources should be allocated to promote the option of treatment and rehabilitation in the community as the least restrictive option. However, if patients' rights are not appropriately kept, public safety may well be compromised, as well as patients' rights. PMID- 17853560 TI - [Terminating patient-physician relationships in primary care: is it the patient's sole privilege?]. AB - Fair patient - physician relationships are essential in primary care. Rare events may violate this delicate and crucial balance to create a reality in which not only the patient can execute the right of "choosing". The physician as well, might (after a properly constructed procedure of attempting all modes of client communication approach, and a complementary organization-initiated investigation) segregate from a problematic patient by offering an alternative and qualitative primary care solution. The article deals with scenarios that define such unique and grave situations, in order to postulate possible pathways to combat the issue reasonably. PMID- 17853561 TI - [The importance of sexual orientation in the medical consultation]. AB - Gay, lesbian, bisexual and transgender (GLBT) patients have unique and different health needs other then those of the heterosexual patient. Although a significant proportion of the population is gay or lesbian, physicians receive little formal training about homosexuality, and the unique health care needs of these patients are often ignored. GLBT patients may have higher rates of depression, suicide attempts, alcoholism, and certain cancers, sexual transmitted and cardiovascular disease. One of the most significant medical risks of these populations is avoidance of routine health care and dissatisfaction due to fear of stigmatization by the medical community. Youth GBLT patients are particularly vulnerable to internal and external pressures, resulting in higher rates of substance and alcohol abuse, suicide, and homelessness. Declining health and loneliness may trouble older GBLT patients, who generally view themselves more positively. Physicians can improve the health care of GBLT patients and their families by maintaining a non-homophobic attitude toward these patients, distinguishing sexual behavior from sexual identity, communicating with gender neutral terms, and maintaining awareness of how their own attitude affects clinical judgment. Scant research exists with regard to the best ways to teach medical students about the special challenge GBLT patients face. However, the recommendation is to integrate such teaching throughout the entire medical school curriculum. This article includes a summary of the medical literature for the GBLT patients' health care needs and suggests strategies for enhancing the care for this population, as well as incorporating it during the medical education. PMID- 17853562 TI - [Clinical guidelines for diagnosis and treatment of acute low back pain]. AB - The purpose of clinical practice guidelines is to delineate an evidence-based common approach to a prevalent medical problem. A decade ago, Guidelines for Acute Low Back Pain (ALBP) care were published in Israel. This year, updated and upgraded guidelines were disseminated, sponsored by the IMA. In the present paper a summary of the new ALBP is reported, as well as a comparison with the prior 1996 guidelines. An evidence tag is attached to each recommendation, enabling the practitioner to examine his deliberations against the existing evidence. The guidelines are adapted from a recent European multidisciplinary document and will remain valid with periodic updating. Clinical practice guidelines are not intended to replace your careful clinical judgment and personal acquaintance with the patient in front of you. They may support your decisions by bringing you a summary of the existing evidence in the domain. PMID- 17853564 TI - Balding wrinkled and stoned. PMID- 17853563 TI - [FUO (fever of unknown origin) as a presenting sign of West Nile fever]. AB - West Nile fever is an infection affecting thousands of people each year, and is responsible for a wide spectrum of clinical manifestations from a mild febrile illness to lethal encephalitis. The prevalence of this infection and its associated morbidity has risen dramatically in recent years. We present a patient with non-specific complaints and prolonged fever for 7 weeks. He underwent thorough investigation, which almost ended with abdominal laparoscopy until the final diagnosis of West Nile Fever was established. PMID- 17853565 TI - Why are these frogs croaking? PMID- 17853566 TI - Is bird flu overhyped? PMID- 17853567 TI - How Bill put the fizz in the fight against fat. PMID- 17853568 TI - Inside the autistic mind. PMID- 17853569 TI - A tale of two schools. PMID- 17853570 TI - Bye bye birdies. PMID- 17853571 TI - Sleep all day! PMID- 17853572 TI - Being 13. PMID- 17853574 TI - You wanna take this online? PMID- 17853573 TI - Is middle school bad for kids? PMID- 17853575 TI - The push to be perfect. PMID- 17853576 TI - Feels like teen spirit. PMID- 17853577 TI - What they won't tell you, and why. PMID- 17853578 TI - Let's have no more monkey trials. To teach faith as science is to undermine both. PMID- 17853580 TI - The right Rx for sadness. PMID- 17853581 TI - A wish list for next year. PMID- 17853579 TI - A gamble on substance. PMID- 17853582 TI - A downside of statins? PMID- 17853583 TI - America's best hospitals. PMID- 17853584 TI - Navigating the hospital. PMID- 17853585 TI - To build a knee. Done right, it's fast, safe, and effective. PMID- 17853586 TI - Replace, wince, repeat. How I cast off my bum right hip, then did it again. PMID- 17853587 TI - Why aren't hospitals cleaner? PMID- 17853588 TI - Medicine, the art. PMID- 17853589 TI - What it takes to be the best. Just 173 medical centers made the cut. Here's how this select handful did it. PMID- 17853590 TI - The gift of a cure. Donating your newborn's umbilical cord might someday save a life. PMID- 17853591 TI - Safely slathered up. The newest sunscreens create a better shield against UVA rays. PMID- 17853592 TI - Alone in a parallel life. PMID- 17853593 TI - Attack of the mutant rice. PMID- 17853594 TI - Microsporidian parasites of mosquitoes. PMID- 17853595 TI - Ascogregarine parasites as possible biocontrol agents of mosquitoes. PMID- 17853596 TI - Mosquito pathogenic viruses--the last 20 years. AB - There are several types of viral pathogens that cause disease in mosquitoes with most belonging to 4 major groups. The most common viruses of mosquitoes are the baculoviruses (NPVs) (Baculoviridae: Nucleopolyhedrovirus) and cytoplasmic polyhedrosis viruses (CPVs) (Reoviridae: Cypovirus). The other major types of viruses in mosquitoes are represented by the densoviruses (DNVs) (Parvoviridae: Brevidensovirus) and the iridoviruses (MIVs) (Iridoviridae: Chloriridovirus). Baculoviruses, densoviruses and iridoviruses are DNA viruses while cypoviruses are the main RNA viruses in mosquitoes. This chapter presents an overview of the recent advancements in the study of mosquito pathogenic viruses and discusses how this new understanding of virus-mosquito interactions can be used to develop novel research and control strategies. PMID- 17853597 TI - Oomycetes: Lagenidium giganteum. AB - Lagenidium giganteum is a facultative parasite of mosquito larvae that initiates infection by production of biflagellate zoospores that selectively recognize and attach to larval cuticle. Following penetration of the cuticle, the parasite proliferates within the host, killing it within 24-60 h. Under optimum conditions the mycelia differentiate to produce asexual and/or sexual reproductive structures that produce zoospores within hours (asexual stage) to amplify the initial infection, or remain dormant for days, months or years (sexual stage), until conditions are conducive to mosquito breeding and spore germination. Recycling following a single application has been documented for up to 8-10 years. Environmental conditions that reduce or eliminate zoospore production, including temperature extremes (less than 16 degrees C or greater than 32 degrees C) and moderate levels of salinity and organic load, preclude use of the parasite for operational mosquito control. Three formulations of L. giganteum have been registered with the USEPA. Widespread use of the parasite will be possible when yields of the sexual stage in liquid culture are increased by a factor of ca. 10(2). PMID- 17853598 TI - Mermithid nematodes. PMID- 17853599 TI - Cyclopoid copepods. AB - Cyclopoid copepods have proved more effective for practical mosquito control than any other invertebrate predator of mosquito larvae. Their operational potential is enhanced by the fact that mass production is relatively easy and inexpensive. The exceptional potential of copepods for mosquito control was first realized about 25 years ago. Since then, laboratory experiments with copepods and mosquito larvae around the world have shown: Only the larger copepod species (body length > 1.4 mm) are of practical use for mosquito control. They kill mainly 1st instar mosquitoes. The most effective species have the capacity to kill more than 40 Aedes larvae/copepod/day. They generally kill fewer Anopheles larvae and even fewer Culex larvae. Most field testing of copepods has been in Aedes container breeding habitats. Field tests have shown that: The most effective copepod species maintain large populations in a container habitat for as long as there is water. They typically reduce Aedes production by 99-100%. They can cause local eradication of container-breeding Aedes mosquitoes if present in a high percentage of breeding sites. Field surveys in Anopheles, floodwater Aedes, and Culex breeding habitats have shown that natural copepod populations can substantially reduce, or even eliminate, mosquito production. Field trials in temporary pools, marshes, and rice fields have demonstrated that introduction of the right copepod species to the right habitat at the right time can eliminate Anopheles or floodwater Aedes larvae. As a rule, copepods cannot eliminate Culex production by themselves, but they can reinforce and augment control by other methods. The only large-scale operational use of copepods to date has been in Vietnam, which has achieved local eradication of Ae. aegypti in hundreds of villages. Conditions in Vietnam are particularly favorable because: Many Ae. aegypti breeding sites are water storage containers that are conspicuous and easily treated. Motivation to maintain copepods in containers for Ae. aegypti control is strong because of the high incidence of dengue hemorrhagic fever. Copepod use is effectively managed by women's associations already experienced with neighborhood health services. Copepods have the potential for local eradication of Ae. aegypti and Ae. albopictus in many other countries besides Vietnam. Professional capacity for copepod management and social institutions for community participation to help with implementation and maintenance are the main factors limiting broader use of copepods for operational mosquito control at the present time. PMID- 17853600 TI - Insects and other invertebrate predators. PMID- 17853601 TI - Aquatic insects as predators of mosquito larvae. PMID- 17853602 TI - Toxorhynchites as biocontrol agents. AB - Toxorhynchites is an unusual and interesting genus of large, non-biting mosquitoes. In spite of their size, they are--like many species of mosquitoes- completely harmless to man. The larvae are predaceous on other mosquitoes and aquatic organisms that inhabit both natural and artificial containers. Because this habitat is the source of several medically important species of mosquitoes, there is warrant for evaluating the potential of Toxorhynchites as a biological control agent under various conditions. Toxorhynchites is not seen as a panacea for the control of all container-inhabiting mosquitoes. However, it has demonstrated practical potential in certain restricted but important situations. PMID- 17853603 TI - Toxorhynchites. PMID- 17853604 TI - Bacillus thuringiensis serovariety israelensis and Bacillus sphaericus for mosquito control. AB - Since the discovery of Bacillus thuringiensis (Berliner) serovariety israelensis de Barjac (Bti) and efficacious isolates of Bacillus sphaericus Neide, formulations of these bacteria have become the predominant non-chemical means employed for control of mosquito larvae at several locations in the United States and other countries. An overview of developments in the past 20 years is presented in this chapter regarding the toxins of Bti and B. sphaericus, their modes of action, efficacy and factors that affect larvicidal activity, development of resistance, safety, and their roles in integrated mosquito control. The efficacy of Bti formulations has been demonstrated in a variety of habitats against a multitude of species of mosquitoes. B. sphaericus formulations have been utilized predominantly in organically enriched habitats against Culex species, but they are also active in a variety of habitats having low organic enrichment, against numerous species, and across several genera. Stegomyia spp. are not susceptible to practical doses of B. sphaericus formulations. B. sphaericus has been shown to persist longer than Bti in polluted habitats and, under certain circumstances, can recycle in larval cadavers. A disadvantage of B. sphaericus has been the development of resistance in certain populations of Cx. quinquefasciatus Say and Cx. pipiens Linnaeus. Biotic and abiotic factors that influence the larvicidal activity of Bti and B. sphaericus include species of mosquito and their respective feeding strategies, rate of ingestion, age and density of larvae, habitat factors (temperature, solar radiation, depth of water, turbidity, tannin and organic content, presence of vegetation, etc.), formulation factors (type of formulation, toxin content, how effectively the material reaches the target, and settling rate), storage conditions, production factors, means of application and frequency of treatments. Due to their efficacy and relative specificity, both Bti and B. sphaericus can be ideal control agents in integrated programs especially where other biological control agents, environmental management, personal protection and the judicious use of insecticides are combined. PMID- 17853605 TI - Developing recombinant bacteria for control of mosquito larvae. AB - Genetic engineering techniques have been used to significantly improve mosquito larvicides based on the bacteria Bacillus thuringiensis (Bt) subsp. israelensis (Bti) and Bacillus sphaericus (Bs). These new larvicides hold excellent promise for providing better and more cost-effective control of nuisance mosquitoes and vectors of important diseases, including the anopheline vectors of malaria and culicine vectors responsible for filariasis and viral encephalitides. The toxicity of Bti and Bs is due primarily to endotoxin proteins produced during sporulation. After ingestion by larvae, these are activated and destroy the larval stomach, quickly resulting in death. By cloning the genes encoding various endotoxins from Bt and Bs species, and engineering these for high levels of synthesis, we have been able to generate recombinant bacterial strains based on Bti that are more than 10 times as effective as the conventional strains of Bti or Bs that serve as the active ingredients of commercial bacterial larvicides currently used for mosquito control. The best of these recombinants contain all major Bti endotoxins, specifically, Cry4A, Cry4B, Cry11A, and Cyt1A, plus the binary (Bin) endotoxin of Bs, the principal mosquitocidal protein responsible for the activity of this species. The presence of Cyt1A in these recombinants, which synergizes Cry toxicity and delays resistance to these proteins and Bs Bin, should enable long term use of these recombinants with little if any development of resistance. In the field, these new recombinants should be particularly effective larvicides against most important vectors and nuisance species of the genus Culex, the malaria vectors Anopheles gambiae and An. arabiensis, and species of Aedes and Ochlerotatus sensitive to Bs. PMID- 17853606 TI - Larvivorous fish including Gambusia. PMID- 17853607 TI - Turtles. AB - Juvenile turtles have the capacity to eat more than 500 3rd and 4th instar mosquitos per day. Keeping one turtle in each water-storage tank during field trials for a dengue-control project in Honduras eliminated all mosquito production from the tanks. In Louisiana, keeping turtles in residential roadside ditches polluted by septic-tank effluent reduced Culex quinquefasciatus larvae and pupae by more than 99%. Turtles can serve as alternate hosts for Salmonella when kept in small pet containers, but the available evidence indicates that turtles create no Salmonella hazard in water-storage tanks or other mosquito breeding habitats. Although turtles would probably not be practical for mosquito control in roadside ditches, they could be effective in storm-water catch basins or holding ponds. PMID- 17853608 TI - Methoprene. AB - A brief overview is presented of the discovery and development of s-methoprene and some other juvenile hormone mimics. The identification of the natural juvenile hormones is described along with an outline of the part they play in the hormonal control of insect development. The properties and commercial applications of s-methoprene are presented with emphasis on its use in mosquito control and its minimal impact on the environment. PMID- 17853609 TI - Semiochemicals, traps/targets and mass trapping technology for mosquito management. AB - Technologies which utilize semiochemicals, traps/targets and mass trapping are relatively new for management of adult mosquito populations. To date most of the emphasis has been on developing barriers of attractant-baited and insecticide impregnated targets. The most successful continuous use of this type of technology has been at Stevens' Landing, Collier County, FL. Recently, commercially available traps have been evaluated for their ability to reduce nuisance populations of mosquitoes. Use of Mosquito Magnet Pro traps along a nature trail on an isolated island (Atsena Otie) in the Gulf of Mexico resulted in a significant reduction in annoyance caused by the black salt marsh mosquito Ochlerotatus taeniorhynchus (Wiedemann). This chapter presents a brief discussion of semiochemicals (behavior modifying) and mosquito traps, strategies for using them for insect control, and an overview of the recent advancements in research activities conducted to evaluate using combinations of semiochemicals and mass trapping techniques for adult mosquito management. PMID- 17853610 TI - Modeling and biological control of mosquitoes. AB - Models can be useful at many different levels when considering complex issues such as biological control of mosquitoes. At an early stage, exploratory models are valuable in exploring the characteristics of an ideal biological control agent and for guidance in data collection. When more data are available, models can be used to explore alternative control strategies and the likelihood of success. There are few modeling studies that explicitly consider biological control in mosquitoes; however, there have been many theoretical studies of biological control in other insect systems and of mosquitoes and mosquito-borne diseases in general. Examples are used here to illustrate important aspects of designing, using and interpreting models. The stability properties of a model are valuable in assessing the potential of a biological control agent, but may not be relevant to a mosquito population with frequent environmental perturbations. The time scale and goal of proposed control strategies are important considerations when analyzing a model. The underlying biology of the mosquito host and the biological control agent must be carefully considered when deciding what to include in a model. Factors such as density dependent population growth in the host, the searching efficiency and aggregation of a natural enemy, and the resource base of both have been shown to influence the stability and dynamics of the interaction. Including existing mosquito control practices into a model is useful if biological control is proposed for locations with current insecticidal control. The development of Integrated Pest Management (IPM) strategies can be enhanced using modeling techniques, as a wide variety of options can be simulated and examined. Models can also be valuable in comparing alternate routes of disease transmission and to investigate the level of control needed to reduce transmission. PMID- 17853611 TI - Population dynamics. AB - This chapter reviews aspects of population dynamics that may be conceptually important for biological control of mosquitoes. Density dependent population regulation among immature stages has important implications for biological control of mosquito populations, primarily because it can lead to compensatory or overcompensatory mortality due to additions of a biological control agent. This can result in control efforts leading to no change in the target population, or actual increases in the target population, respectively. Density dependent effects, and compensatory or overcompensatory mortality, appear to be most common in mosquitoes from container or highly ephemeral habitats. In permanent ground water habitats generalist predators appear to limit mosquito populations and so render mortality additive. Thus, biological control in permanent ground water habitats seems to have the highest likelihood of producing a satisfactory result. A central premise of classical biological control is that pest populations are reduced by enemies to stable equilibrium levels that are both below the pre control equilibrium level, and well below the level producing detrimental effects. This premise results in predictions that successful biological control is likely to involve specialist enemies (usually parasitoids), with short generation times relative to the victim, high rates of successful search, rapid rates of increase, and needing only a few victims to complete their life cycle. These predictions largely fail for mosquito systems, in which successful biological control seems to be associated with generalist enemies that can kill a large portion of the target population, often causing local extinction, and can persist in the absence of the target organism. Biological control of mosquitoes appears to be inherently unstable, thus contrasting sharply with classical biological control. This review suggests a need for better data on density dependent regulation of mosquito populations. PMID- 17853612 TI - Competitive displacement and reduction. PMID- 17853613 TI - The molecular genetics of larval mosquito biology: a path to new strategies for control. PMID- 17853614 TI - Regulatory considerations with biological control of public health pests. PMID- 17853615 TI - Fluorescence microlymphography: diagnostic potential in lymphedema and basis for the measurement of lymphatic pressure and flow velocity. AB - Fluorescence microlymphography (FML) is an almost atraumatic technique used to visualize the superficial skin network of initial lymphatics through the intact skin of man. Visualization was performed with an incident light fluorescence microscope following subepidermal injection of minute amounts of FITC-dextran 150,000 using microneedles. Emanating from the bright dye depot, the surrounding network of microvessels is filled, documentation performed by photography or video film. In congenital Milroy lymphedema, a lack of microlymphatics (aplasia) is typical while in other primary lymphedemas and in secondary lymphedema after mastectomy or irradiation of proximal lymph nodes, the network remains intact but the depicted area is enlarged. Lymphatic microangiopathy characterized by obliterations of capillary meshes or mesh segments develops in phleboedema with trophic skin changes, progressive systemic sclerosis and Fabry's disease. In lipedema, lymphatic microaneurysms are stained. Microlymphatic pressure may also be measured using FML. For this purpose, glass micropipettes are inserted into the capillaries by means of a micromanipulator and pressure is determined by the servo-nulling technique. Normal subjects produced significantly lower pressure (7.9 +/- 3.4 mmHg) compared to patients with primary lymphedema (15.0 +/- 5.1 mmHg, p<0.001). This characteristic lymphatic hypertension may be improved by complex physiotherapy or local application of prostaglandins. Additionally, a modification of the FML procedure can be used to measure lymphatic capillary flow velocity in controls and patients. FML is suited to confirm the clinical diagnosis of lymphedema, contributes to distinguish among various forms of edema, and is useful in clinical research. In addition, FML has also become a tool for experimental animal studies including the depiction of gastric microlymphatics, the measurement of flow velocity in the naked mouse tail, and in evaluation of lymphangiogenesis in a model of Milroy disease. PMID- 17853616 TI - Cutaneous drainage lymphatic map with interstitial multidetector-row computed tomographic lymphography using iopamidol: preliminary results. AB - We performed preliminary tests of the feasibility of multi-detector computed tomographic lymphography (MDCT-LG) with interstitial injection of iopamidol for mapping cutaneous lymphatic drainage pathways. MDCT-LG images were obtained following cutaneous injection of a total of 1ml iopamidol bilaterally into hind legs of 10 dogs. The locations of the first draining lymph nodes were marked on the skin under MDCT-LG guidance. Five dogs served for postmortem examination of lymphatic anatomy, and the remaining 5 underwent MDCT-LG after ligation of the afferent lymphatic vessels of the first draining popliteal nodes. Clinically, MDCT-LG was attempted in 6 patients with cutaneous malignant melanoma and compared with Tc-99m-human serum albumin lymphoscintigraphy. MDCT-LG clearly visualized the first draining lymph nodes and their afferent lymphatic vessels draining from the contrast injection sites with detailed underlying anatomy in all dogs. At surgery, all these first draining nodes could be found at predicted locations under MDCT-LG guidance. MDCT-LG showed rerouting of lymphatic vessels after ligation of the afferent lymph vessels of the popliteal nodes in the second 5 dogs. Clinically, MDCT-LG also allowed accurate mapping and biopsy of the first draining nodes from primary tumors at predicted locations, with minimal skin incision. Lymphoscintigraphy failed to identify these nodes due to overlapping radioactivity of clustered nodes or transport of the radiotracer to subsequent distant nodes in 4 patients. Although a more extensive study is warranted for further validation, preoperative interstitial MDCT-LG appears to have the potential feasibility for accurate sentinel lymph node mapping and biopsy in patients with cutaneous melanoma. PMID- 17853617 TI - Disseminated lymphangiomatosis with skeletal involvement: detection with magnetic resonance lymphangiography. AB - Disseminated lymphangiomatosis is an uncommon disorder characterized by diffuse or multifocal proliferation of complex, irregular lymphatic channels involving soft tissue, viscera, retroperitoneum, eyes and the skeletal system. Currently, magnetic resonance imaging, computed tomography, ultrasonography, and conventional radiography are the favored radiologic imaging modalities in assessing the extent of pathologic changes in patients suffering from disseminated lymphangiomatosis. Historically, imaging evaluation was performed with conventional lymphography. We report on the first patient suffering from disseminated lymphangiomatosis with skeletal involvement, whose lymphatic vasculature of the lower limbs and pelvic region was evaluated with magnetic resonance lymphangiography. PMID- 17853618 TI - Presence of functional axillary lymph nodes and lymph drainage within arms in women with and without breast cancer-related lymphedema. AB - This pilot study was designed to investigate lymphatic transport in the arms of women after breast cancer treatment without lymphedema and with mild and severe arm lymphedema. Nineteen breast cancer survivors [6 without (Group 1), 6 with mild (Group 2) and 7 with severe (Group 3) lymphedema] were examined. Lymphatic transport in the arm and to axillary lymph nodes were evaluated using quantitative radionuclide lymphscintigraphy. The radioactivity ratio between the operated and unoperated axillae (axillary ratio), and both lymphatic transport and tracer disappearance rates (TDR) from the injection sites were calculated. We found that axillary ratio and lymphatic transport were significantly higher in Groups 1 and 2 compared to 3 and that TDR was not affected in any Group. Additionally, lymphscintigraphy revealed presence of functional axillary lymph nodes within the operated axilla in women without or with mild lymphedema, while in women with severe lymphedema, no axillary lymph nodes were visualized. We conclude from our subjects that breast cancer survivors who did not develop or had mild arm lymphedema have functional lymphatic transport and lymph nodes in the axillary area on the operated side. This suggests that efficient collateral circulation and/or peripheral lymphovenous communications has developed in these subjects which may be preventative for the development of severe lymphedema. PMID- 17853619 TI - Assessing local tissue edema in postmastectomy lymphedema. AB - Overall limb lymphedema can be assessed by several methods but none are suitable to determine local edema. Quantifying local edema could provide important information not previously available. Our goal was to determine the suitability of using the tissue dielectric constant (TDC) as and index of local tissue water to detect and quantify edema in postmastectomy patients with unilateral arm lymphedema. Segmental arm volume and TDC were measured in both arms of 18 women with unilateral lymphedema, and in 15 premenopausal and 15 postmenopausal controls. TDC was measured at a frequency of 300 MHz using open-ended coaxial probes with effective measuring depths of 0.5, 1.5, 2.5 and 5.0 mm. For patients and controls, absolute TDC depended on measurement depth but for any depth the TDC of lymphedematous segments was significantly greater than for non-affected contralateral arms (p<0.001). At a depth of 2.5 mm, the TDC ratio between arms for patients was 1.64+/-0.30 vs.1.04+/-0.04 for both control groups (p<0.001). No patient's TDC ratio was as low as 1.2 and no control subject's TDC ratio was as great as 1.2. Results suggest that this method is a good quantitative discriminator of the presence of lymphedema in patients with unilateral limb lymphedema. PMID- 17853620 TI - Silver bullets, shotguns, and integrative community-based approach to lymphedema from lymphatic filariasis in India. PMID- 17853621 TI - Silver bullets, shotguns, and integrative community-based approach to lymphedema from lymphatic filariasis in India. PMID- 17853622 TI - Renal lymphatic drainage and thoracic duct connections. PMID- 17853623 TI - Conflicting evidence on splints for carpal tunnel syndrome. PMID- 17853624 TI - The empty chair. PMID- 17853625 TI - Treatment options for insomnia. AB - The frequency of sleep disruption and the degree to which insomnia significantly affects daytime function determine the need for evaluation and treatment. Physicians may initiate treatment of insomnia at an initial visit; for patients with a clear acute stressor such as grief, no further evaluation may be indicated. However, if insomnia is severe or long-lasting, a thorough evaluation to uncover coexisting medical, neurologic, or psychiatric illness is warranted. Treatment should begin with nonpharmacologic therapy, addressing sleep hygiene issues and exercise. There is good evidence supporting the effectiveness of cognitive behavior therapy. Exercise improves sleep as effectively as benzodiazepines in some studies and, given its other health benefits, is recommended for patients with insomnia. Hypnotics generally should be prescribed for short periods only, with the frequency and duration of use customized to each patient's circumstances. Routine use of over-the-counter drugs containing antihistamines should be discouraged. Alcohol has the potential for abuse and should not be used as a sleep aid. Opiates are valuable in pain-associated insomnia. Benzodiazepines are most useful for short-term treatment; however, long term use may lead to adverse effects and withdrawal phenomena. The better safety profile of the newer-generation nonbenzodiazepines (i.e., zolpidem, zaleplon, eszopidone, and ramelteon) makes them better first-line choices for long-term treatment of chronic insomnia. PMID- 17853626 TI - Information from your family doctor. Insomnia: what you should know. PMID- 17853627 TI - Radiologic evaluation of acute chest pain--suspected myocardial ischemia. AB - The American College of Radiology has developed appropriateness criteria for a number of clinical conditions and procedures. Criteria are available on imaging tests used in the evaluation of acute chest pain--suspected myocardial ischemia. Imaging tests for a suspected cardiac etiology include transthoracic echocardiography, transesophageal echocardiography, radionuclide perfusion imaging, radionuclide ventriculography, radionuclide infarct avid imaging, and positron emission tomography. If the cardiac ischemic work-up is negative or indeterminate, applicable tests include chest radiography; conventional, multidetector, and electron beam computed tomography; and magnetic resonance imaging. A summary of the criteria, with the advantages and limitations of each test, is presented in this article. PMID- 17853628 TI - Vibrio vulnificus infection: diagnosis and treatment. AB - Vibrio vulnificus infection is the leading cause of death related to seafood consumption in the United States. This virulent, gram-negative bacterium causes two distinct syndromes. The first is an overwhelming primary septicemia caused by consuming raw or undercooked seafood, particularly raw oysters. The second is a necrotizing wound infection acquired when an open wound is exposed to warm seawater with high concentrations of V. vulnificus. Most patients, including those with primary infection, develop sepsis and severe cellulitis with rapid development to ecchymoses and bullae. In severe cases, necrotizing fasciitis can develop. Case-fatality rates are greater than 50 percent for primary septicemia and about 15 percent for wound infections. Treatment of V vulnificus infection includes antibiotics, aggressive wound therapy, and supportive care. Most patients who acquire the infection have at least one predisposing immunocompromising condition. Physician awareness of risk factors for V. vulnificus infection combined with prompt diagnosis and treatment can significantly improve patient outcomes. (Am Fam Physic PMID- 17853629 TI - Information from your family doctor. Vibrio vulnificus infection: what you should know. PMID- 17853630 TI - Herbal and dietary supplements for treatment of anxiety disorders. AB - Use of complementary and alternative medicine has increased over the past decade. A variety of studies have suggested that this use is greater in persons with symptoms or diagnoses of anxiety and depression. Data support the effectiveness of some popular herbal remedies and dietary supplements; in some of these products, particularly kava, the potential for benefit seems greater than that for harm with short-term use in patients with mild to moderate anxiety. Inositol has been found to have modest effects in patients with panic disorder or obsessive-compulsive disorder. Physicians should not encourage the use of St. John's wort, valerian, Sympathyl, or passionflower for the treatment of anxiety based on small or inconsistent effects in small studies. Although the evidence varies depending on the supplement and the anxiety disorder, physicians can collaborate with patients in developing dietary supplement strategies that minimize risks and maximize benefits. PMID- 17853631 TI - Predicting pneumonia in adults with respiratory illness. PMID- 17853632 TI - Yellow-white retinal lesion in a 48-year-old woman. Cytomegalovirus (CMV) retinitis. PMID- 17853633 TI - Consent, communication, surgery, body donation, and the Human Tissue Act. PMID- 17853634 TI - Pakistan, population programmes and progress. PMID- 17853635 TI - The Human Tissue Act (2004), anatomical examination and the importance of body donation in Northern Ireland. PMID- 17853636 TI - The use of mechanical bowel preparation in elective colorectal surgery. AB - BACKGROUND: Mechanical bowel preparation (MBP) prior to elective colorectal surgery has been in use for many years. It is considered important in preventing post-operative infectious complications after colorectal surgery. The evidence to support these claims is lacking within the medical literature and yet this still remains standard practice in many hospitals. A literature search was undertaken to ascertain the evidence available regarding the use of MBP in elective colorectal surgery. METHODS: The search included the databases PubMed, Medline and Embase using the keywords "mechanical bowel preparation", "bowel cleansing" and "elective colorectal surgery", a search of recent issues of relevant journals including Diseases of the Colon and Rectum and British Journal of Surgery and backward chaining from articles obtained. RESULTS AND CONCLUSION: Most authors recommend that colorectal surgery is safe without pre-operative MBP but that there may some situations in which it may be beneficial (e.g. if there is a small tumour or the possible need for intra-operative colonoscopy). The implication for clinical practice in this situation is that there is not enough strength of evidence at present to recommend a change in practice. There is a need for further higher powered trials to try to answer this question definitively. PMID- 17853637 TI - Transformation of cytogenetically normal chronic myelomonocytic leukaemia to an acute myeloid leukaemia and the emergence of a novel +13, +15 double trisomy resulting in an adverse outcome. AB - A 58-year-old man was admitted with symptoms of lethargy and easy bruising for four months duration. Peripheral blood (PB) analysis revealed a white blood cell count (WBC) of 15.9 x 10(9)/l with monocytes 5.4 x 10(9)/l. Bone marrow (BM) was hypercellular with 15% blasts, monocytosis and trilineage dysplasia. Conventional cytogenetic analysis (G-banding) detected an apparently normal male karyotype (46,XY). A diagnosis of chronic myelomonocytic leukaemia (CMML) was made. After 3 years, PB analysis revealed a WBC count of 22 x 10(9)/l and a predominance of blasts. BM aspirate analysis also revealed 89% myeloid blasts and G-banding detected the emergence of an abnormal clone harbouring an extra copy of chromosomes 13 and 15. A diagnosis of disease transformation to acute myeloid leukaemia (AML) was made. Post chemotherapy BM aspirate was very hypocellular and the abnormal +13, +15 clone was still present suggesting primary refractory disease. A second course of chemotherapy was only administered for 24 hours due to complications. The abnormal +13, +15 clone was still present and it was decided that no further treatment apart from palliative care could be offered. The patient died 11 weeks later, five months after AML transformation. This is the first description of a cytogenetically normal CMML patient transforming to AML with the emergence of a unique +13, +15 double trisomy resulting in an adverse outcome. PMID- 17853638 TI - Chronic pain after hernia surgery--an informed consent issue. AB - Chronic severe pain following inguinal hernia repair is a significant post operative problem. Its exact cause and lack of evidence-based treatment path present problems in the effective management of this surgical complication. We retrospectively reviewed the records of patients diagnosed with chronic pain following open inguinal hernia repair between November 1995 and November 2000, who were under the care of the senior author. Over the five-year period, 146 patients underwent inguinal hernia repair. 88 (60%) had suture repair (darn & modified Bassini's) and 58 (40%) underwent a Lichtenstein mesh repair. Thirteen patients (9%), (3 in suture vs. 10 in mesh group, p = 0.004) developed chronic severe pain. Examination revealed maximal tenderness over the genitofemoral nerve (GF) distribution (n = 5), over the medial end of the scar (n = 3), over the pubic tubercle (n = 1) and in the ilioinguinal nerve distribution (n = 1) No abnormality was detected on clinical examination in the cases of three patients. Treatment involved GF nerve block (n = 5), local injection of Chirocaine and Methylprednisolone acetate into the medial end of the scar (n = 3), Chirocaine and Methylprednisolone acetate into the pubic tubercle (n = 1), ilioinguinal nerve block (n = 1), re-exploration with re-suturing of the mesh (n = 1), and Amitriptyline (n = 2). At a median follow up of 45 months (range: 24-87), 10 (77%) are completely pain free; two (15.4%) had mild pain and one patient still has significant persistent pain. To conclude, chronic severe pain occurred in nine percent of patients following primary open inguinal hernia repair. The majority of patients were successfully treated by therapeutic injection into the point of maximal tenderness. PMID- 17853639 TI - 'Doctor--when can I drive?'--Advice obstetricians and gynaecologists give on driving after obstetric or gynaecological surgery. AB - Advising patients when to drive after surgery is a common practice which gynaecologists need to do on a regular basis as a part of their duty to patients. We carried out a literature search regarding advice given on driving after gynaecological surgical procedures, and found no study or research on this area. We then carried out a questionnaire survey of 99 gynaecologists in Northern Ireland. We have identified wide variation in clinical practice, and advocate a United Kingdom wide survey and further studies to find out optimum time to drive after different gynaecological surgeries. There is a need for national guidelines on driving after surgery, which would be of great benefit to gynaecologists, patients, motor insurers, police and all other interested parties. PMID- 17853640 TI - Assessment of fertility control efforts in a selected area of Karachi, Pakistan. AB - AIMS: To investigate the impact of fertility control efforts on reducing fertility and to study the contributory role of fertility inhibiting factors viz, age of the marriage, breast feeding and post-partum amenorrhea, abortion and use of contraceptives in selected area in Karachi, Pakistan. The aim was to estimate the gap between knowledge of contraceptives and its practice i.e. KAP-GAP as well as to determine the level of unmet need in the PIB colony in Karachi. DATA SOURCE: A sample survey was conducted in PIB colony in Karachi from October 2005 to November 2005 by interviewing 340 married women in reproductive ages. The data was tabulated and John Bongaarts technique was used to analyse the success of fertility control efforts in the selected area. RESULTS: Of the total of 340 respondents, 38% were currently using contraceptive methods with 26% using OCP's and 12% were condom users. A slight reduction in total fertility (TFR) was noticed. CONCLUSION: The population policy of Pakistan envisages achieving population stabilization in 2020 by reducing the annual rate of population growth from 1.9% to 1.3% and TFR at 2.1. This target requires strenuous efforts to make the concept of small family an accepted milieu through an eagerly designed communication and education campaign. Concentration on proximate determinants of fertility particularly breast feeding and prolonging birth interval will not generate opposition from the community because these concepts are in accordance with Islamic injunctions and teachings. PMID- 17853641 TI - Five year follow-up comparing tension-free vaginal tape and colposuspension. AB - Burch colposuspension has been the procedure of choice for stress urinary incontinence, more recently the tension-free vaginal tape (TVT) has been used. A retrospective study on all TVT's and colposupensions was performed. The present clinical condition was assessed using the Bristol Female Lower Urinary Tract Symptoms and Short-Form 12 questionnaires. The median operating time was 50-59 minutes for TVT and 70-79 minutes for colposupension. The median number of day's hospitalization was 3 and 10 respectively. The overall success rate was 88.5% and 92% respectively. No significant difference in subjective outcome was noted at more than 5 years after surgery between the two procedures for either the BFLUTS or SF-12. PMID- 17853642 TI - Prospective survey of serial troponin T requesting in an acute teaching hospital. AB - BACKGROUND: Requests for troponin T, a biomarker for myocardial infarction, may be sent in a variety of clinical situations. In most cases, a single sample 12 hours or more after symptom onset should be sufficient for diagnosis. We chose to investigate how troponin T testing is used in our hospital with emphasis on those who had serial rather than single troponin measurements during their hospital stay. METHODS: Prospective survey of 50 patients with serial troponin T requests out of a total of 321 patients who had troponin T levels measured during the same time period. RESULTS: The time of symptom onset could be clearly identified in 40/50 patients. In 22 of these the first troponin was taken prior to 12 hours after symptom onset. For the 18 patients whose first troponin was taken after 12 hours, the second result remained in the same category (normal or high) as the first in all cases. This was not the case for 3/10 patients whose first troponin was sent within 12 hours and was normal. Early troponin results rarely affected immediate patient management and did not inform decisions about fibrinolytic therapy. CONCLUSIONS: Serial troponin testing was most commonly due to a sample being sent within 12 hours of symptom onset or to unnecessary repetition of an appropriately timed sample. Patient management was rarely enhanced by early troponin testing. PMID- 17853643 TI - Using estimated glomerular filtration rate (eGFR) to help manage patients with chronic kidney disease. PMID- 17853644 TI - ART and prejudice. PMID- 17853645 TI - Thorn injury mimicking a septic arthritis of the knee. PMID- 17853646 TI - Complete laparoscopic management of cholecystocutaneous fistula. PMID- 17853647 TI - Primary hyperparathyroidism and its management in a woman with hereditary long QT syndrome. PMID- 17853648 TI - Follow up after PEG tube insertion. PMID- 17853649 TI - Symptomatic hyperphosphataemia following phosphate enema in a healthy adult. PMID- 17853650 TI - Perianal leiomyoma involving the anal sphincter. PMID- 17853651 TI - Respiratory complications of spinal cord injury. PMID- 17853652 TI - Respiratory management during the first five days after spinal cord injury. AB - Respiratory complications are the most common cause of morbidity and mortality in acute spinal cord injury (SCI), with an incidence of 36% to 83%. Eighty percent of deaths in patients hospitalized with cervical SCI are secondary to pulmonary dysfunction, with pneumonia the cause in 50% of the cases. The number of respiratory complications during the acute hospital stay contributes significantly to the length of hospital stay and cost. Four factors (use of mechanical ventilation, pneumonia, the need for surgery, and use of tracheostomy) explain nearly 60% of hospital costs and may be as important a predictor of hospital cost as level of injury. Atelectasis (36.4%), pneumonia (31.4%), and ventilatory failure (22.6%) are the most common complications during the first 5 days after injury. Ventilatory failure occurs on average 4.5 days after injury. Transfer to an SCI center specializing in acute management of tetraplegia has been shown to significantly reduce the number of respiratory complications. This review concentrates on the first 5 days after injury, focusing on complications, predictive factors, prevention, and management of those complications. PMID- 17853653 TI - Effect of spinal cord injury on the respiratory system: basic research and current clinical treatment options. AB - Spinal cord injury (SCI) often leads to an impairment of the respiratory system. The more rostral the level of injury, the more likely the injury will affect ventilation. In fact, respiratory insufficiency is the number one cause of mortality and morbidity after SCI. This review highlights the progress that has been made in basic and clinical research, while noting the gaps in our knowledge. Basic research has focused on a hemisection injury model to examine methods aimed at improving respiratory function after SCI, but contusion injury models have also been used. Increasing synaptic plasticity, strengthening spared axonal pathways, and the disinhibition of phrenic motor neurons all result in the activation of a latent respiratory motor pathway that restores function to a previously paralyzed hemidiaphragm in animal models. Human clinical studies have revealed that respiratory function is negatively impacted by SCI. Respiratory muscle training regimens may improve inspiratory function after SCI, but more thorough and carefully designed studies are needed to adequately address this issue. Phrenic nerve and diaphragm pacing are options available to wean patients from standard mechanical ventilation. The techniques aimed at improving respiratory function in humans with SCI have both pros and cons, but having more options available to the clinician allows for more individualized treatment, resulting in better patient care. Despite significant progress in both basic and clinical research, there is still a significant gap in our understanding of the effect of SCI on the respiratory system. PMID- 17853654 TI - Differential expression of adenosine A1 and A2A receptors after upper cervical (C2) spinal cord hemisection in adult rats. AB - BACKGROUND: In an animal model of spinal cord injury, a latent respiratory motor pathway can be pharmacologically activated via adenosine receptors to restore respiratory function after cervical (C2) spinal cord hemisection that paralyzes the hemidiaphragm ipsilateral to injury. Although spinal phrenic motoneurons immunopositive for adenosine receptors have been demonstrated (C3-C5), it is unclear if adenosine receptor protein levels are altered after C2 hemisection and theophylline administration. OBJECTIVE: To assess the effects of C2 spinal cord hemisection and theophylline administration on the expression of adenosine receptor proteins. METHODS: Adenosine A1 and A2A receptor protein levels were assessed in adult rats classified as (a) noninjured and theophylline treated, (b) C2 hemisected, (c) C2 hemisected and administered theophylline orally (3x daily) for 3 days only, and (d) C2 hemisected and administered theophylline (3x daily for 3 days) and assessed 12 days after drug administration. Assessment of A1 protein levels was carried out via immunohistochemistry and A2A protein levels by densitometry. RESULTS: Adenosine A1 protein levels decreased significantly (both ipsilateral and contralateral to injury) after C2 hemisection; however, the decrease was attenuated in hemisected and theophylline-treated animals. Attenuation in adenosine A1 receptor protein levels persisted when theophylline administration was stopped for 12 days prior to assessment. Adenosine A2A protein levels were unchanged by C2 hemisection; however, theophylline reduced the levels within the phrenic motoneurons. Furthermore, the decrease in A2A levels persisted 12 days after theophylline was withdrawn. CONCLUSION: Our findings suggest that theophylline mitigates the effects of C2 hemisection by attenuating the C2 hemisection-induced decrease in A1 protein levels. Furthermore, A2A protein levels are unaltered by C2 hemisection but decrease after continuous or interrupted theophylline administration. The effects on protein levels may underlie the stimulant actions of theophylline. PMID- 17853655 TI - Microstimulators and intramuscular hook electrodes for the stimulation of respiratory muscles. AB - BACKGROUND/OBJECTIVES: We determined the feasibility of stimulating the major muscles of respiration with different types of electrodes. Intramuscular hook electrodes, model microstimulators (M-Micro) developed in our laboratory, and commercial radiofrequency microstimulators (RFM) (Alfred Mann Foundation, Valencia, CA), were employed in this investigation. METHODS: In 8 anesthetized dogs, M-Micro were placed bilaterally on the diaphragm and in the abdominal muscles, and hook electrodes were placed in the 3rd and 5th intercostal regions adjacent to the intercostal nerves known to support inspiration. In 3 of the 8 animals, RFMs (Alfred Mann Foundation) in addition to the M-Micros were sutured to each hemidiaphragm at the same optimal site for phrenic nerve stimulation. During a hyperventilation-induced apnea, 2-second stimulations were applied to the diaphragm and with various combinations of diaphragm plus supporting muscles, both thoracic and abdominal. RESULTS: Diaphragm stimulation alone provided tidal volumes adequate for basal alveolar ventilation. However, implantation of the RFM required greater contact with the muscle. Stimulating other respiratory muscles along with the diaphragm further increased tidal volumes. The hook electrodes, M Micro, and RFM performed equally well. CONCLUSIONS: In the acute dog model, M Micro and hook electrodes can provide an implant system for the maintenance of ventilation. Support of the intercostal and abdominal muscles has the potential to reduce the contraction requirements of the diaphragm with decreased likelihood of diaphragm fatigue and hypoventilation. Whether the electrodes under investigation could provide an implant system for long-term ventilation needs to be determined. PMID- 17853657 TI - Acute respiratory tract infection visits of veterans with spinal cord injuries and disorders: rates, trends, and risk factors. AB - BACKGROUND/OBJECTIVES: Respiratory complications are a major cause of illness and death in persons with spinal cord injuries and dysfunction (SCI&Ds). The objectives of this study were to examine rates of outpatient visits over 5 years for acute respiratory tract infections (ARIs), including pneumonia and influenza (P&I), lower respiratory tract infections (LRIs), and upper respiratory tract infections (URIs), in veterans with SCI&Ds and to determine whether individual characteristics were associated with the number of annual visits for each type of ARI. METHODS: This was a longitudinal (fiscal years 1998-2002) study of ARI visits at the Veterans Health Administration (VA) in 18,693 veterans with SCI&Ds. To examine the associations between time, patient characteristics, and annual number of ARI visits, we used random effect negative binomial models. RESULTS: Veterans with SCI&Ds had a total of 11,113 ARI visits over the 5-year period. There was a slightly decreasing trend for LRI visits over time (P < 0.01) but no significant change for other ARIs over time. There were 30 to 35 pneumonia visits and 21 to 30 acute bronchitis visits per 1,000 SCI&D veterans per year. Older veterans were more likely than younger to have P&I visits and less likely to have URI visits (P < 0.01). Veterans with paraplegia had fewer P&I visits than subjects with tetraplegia (IRR = 0.58; Cl = 0.51-0.67). CONCLUSIONS: Visit rates for ARIs are stable for veterans with SCI&Ds. Identifying risk factors associated with ARI visits is an important first step to improve prevention and treatment of ARIs and to improve the health of veterans with SCI&Ds. PMID- 17853656 TI - MK-801 upregulates NR2A protein levels and induces functional recovery of the ipsilateral hemidiaphragm following acute C2 hemisection in adult rats. AB - BACKGROUND: C2 hemisection results in paralysis of the ipsilateral hemidiaphragm. Recent data indicate that an upregulation of the N-methyl-D-aspartate (NMDA) receptor 2A subunit following chronic C2 hemisection is associated with spontaneous hemidiaphragmatic recovery following injury. MK-801, an antagonist of the NMDA receptor, upregulates the NR2A subunit in neonatal rats. HYPOTHESIS: We hypothesized that administration of MK-801 to adult, acute C2-hemisected rats would result in an increase of NR2A in the spinal cord. Furthermore, we hypothesized that upregulation of NR2A would be associated with recovery of the ipsilateral hemidiaphragm as in the chronic studies. DESIGN: To develop a dose response curve, adult rats were treated with varying doses of MK-801 and their spinal cords harvested and assessed for NR2A as well as AMPA GluR1 and GluR2 subunit protein levels. In the second part of this study, C2-hemisected animals received MK-801. Following treatment, the animals were assessed for recovery of the hemidiaphragm through electromyographic recordings and their spinal cords assessed for NR2A, GluR1, and GluR2. RESULTS: Treatment with MK-801 leads to an increase of the NR2A subunit in the spinal cords of adult noninjured rats. There were no changes in the expression of GluR1 and GluR2 in these animals. Administration of MK-801 to C2-hemisected rats resulted in recovery of the ipsilateral hemidiaphragm, an increase of NR2A, and a decrease of GluR2. CONCLUSION: Our findings strengthen the evidence that the NR2A subunit plays a substantial role in mediating recovery of the paralyzed hemidiaphragm following C2 spinal cord hemisection. PMID- 17853658 TI - Skin response to delayed hypersensitivity testing in persons with unilateral stroke-related paresis: implications for people with spinal cord injury. AB - BACKGROUND: Vaccination rates among individuals with spinal cord injury (SCI) could be improved if it can be shown that vaccination performed on insensate areas is effective. This would eliminate the the risk of discomfort and soreness at the injection site. OBJECTIVE: To determine whether immune responsiveness varies between areas with intact and impaired innervation in patients with stroke related paresis. DESIGN: Prospective trial in which each subject served as his or her own control. SETTING: Rehabilitation wards and long-term care units at a Veterans Affairs Medical Center. PATIENTS: Individuals with a history of cerebrovascular accident (CVA) affecting 1 side of the body. METHODS: The Multitest cell-mediated immunity (CMI) and purified protein derivative (PPD) of tuberculin were administered intradermally to each arm of each subject. MAIN OUTCOME MEASURES: Total millimeters of induration in response to either test and positive vs negative responses to either test were compared between the 2 arms of each subject. RESULTS: Response to delayed hypersensitivity testing did not differ between the arms affected and unaffected by CVA in each subject, and the time since CVA also did not affect the magnitude of the skin response. CONCLUSIONS: Skin testing for delayed hypersensitivity can be effectively administered in the paretic arms of persons who have experienced CVA. Although this study was performed in patients with stroke-related impairment, it has implications for vaccine administration in individuals with SCI-related neurologic deficits. PMID- 17853659 TI - Spinal cord injuries as a result of earthquakes: lessons from Iran and Pakistan. PMID- 17853660 TI - Earthquakes and rehabilitation needs: experiences from Bam, Iran. AB - BACKGROUND: In December 2003, a devastating earthquake destroyed Bam and surrounding areas in Iran, leaving many people with residual deficits and disabilities, of which approximately 240 patients had spinal cord injury (SCI). METHODS: As an independent volunteer working in outpatient clinics, I visited the patients as part of a mobile team and set up a short educational course in spinal cord medicine. RESULTS: I visited 34 patients with SCI in the first 3 months. Eight months after the disaster, I visited 54 patients with SCI, 29 female (53.7%) and 25 male (46.3%). Postdisaster problems were identified, including need for accurate data collection, identification of patients' conditions, attention paid to psychosocial issues, ethical dilemmas, and research needs. CONCLUSION: Disaster preparedness for earthquakes should include first aid and injury prevention, coordination of relief efforts, basic education and medical care, and short-and long-term rehabilitation needs. The major focus of rehabilitation medicine specialists' should be education of the general and professional population toward integrating the concept of rehabilitation. PMID- 17853661 TI - Complications in patients with spinal cord injuries sustained in an earthquake in Northern Pakistan. AB - BACKGROUND: Spinal cord injury (SCI) is a devastating trauma suffered by many of the victims of an earthquake that struck Northern Pakistan on October 8, 2005. It rendered approximately 600 patients paraplegic, which is the highest number ever reported in any disaster. This study was conducted to evaluate the risk of complications. METHODS: The cross-sectional retrospective study covering a 2 month period was conducted on 194 patients admitted to the surgical/neurosurgical wards of Rawalpindi Medical College and allied hospitals (Holy Family Hospital, Rawalpindi General Hospital, and District Headquarter Hospital) and Melody Relief and Rehabilitation Center, Islamabad. RESULTS: The male-to-female ratio was approximately 1:3 (n = 50 [26%] and n = 144 [74%], respectively). The majority (78% [n = 151]) were 16 to 39 years of age; 62% (n = 120) had lumbar-level injuries, 25% (n = 48) had thoracic-level injuries, 9% (n = 18) had thoracolumbar level injuries, and a few had cervical- or sacral-level injuries. Forty-six percent (n = 90) had American Spinal Injury Association type A injuries; 4% (n = 8) were graded B, 11% (n = 21) were graded C, 9% (n = 18) were graded D, and 14% (n = 27) were graded E. Twenty percent (n = 39) developed pressure ulcers, of which 38% (n = 15) had grade 1, 36% (n = 14) had grade 2, 23% (n = 9) had grade 3, and 3% (n = 1) had grade 4. All patients developed urinary tract infections; 15% (n = 30) had bowel complaints; 2% (n = 3) developed deep-vein thrombosis (1 died of pulmonary embolism); and 0.05% (n = 1) developed wound infection. CONCLUSION: Awareness of potential complications in patients with paraplegia is essential to care planning in the disaster setting. The priorities include skin, bowel, and bladder care and provision of prophylactic heparin. SCI post-disaster care requires comprehensive long-term planning. PMID- 17853662 TI - Gastric dysmotility after abdominal surgery in persons with cervical spinal cord injury: a case series. AB - BACKGROUND: Spinal cord injury (SCI) has been found to affect the physiology of the gastrointestinal tract. Changes in gastric motility occur in tetraplegia because of dissociation of antral and duodenal motility. Among individuals with high-level tetraplegia, antral quiescence has been hypothesized as a manifestation of autonomic dysreflexia after surgery. This case series shows the issues with gastric hypomotility after gastrointestinal surgery in tetraplegic patients with tetraplegia, including management strategies. OBJECTIVE: To report 3 patients with complete high cervical SCI who developed gastroparesis after abdominal surgery and discuss the effect of autonomic dysfunction on gastric motility. METHODS: Retrospective chart review of 3 cases. RESULTS: Gastroparesis occurred after abdominal surgery in 3 patients with C4 American Spinal Injury Association (ASIA) A tetraplegia and seemed to be a sign of autonomic hyperreflexia caused by postoperative pain. Management was challenging because it consisted of balancing of appropriate pain medication and dealing with absorption issues and dysmotility. Often gastric motility agents were not effective in improving gastric emptying. However, increased use of pain medication improved gastric emptying, which supports the hypothesis that this issue represents gastric dysfunction from autonomic hyperreflexia. CONCLUSIONS: In persons with complete cervical SCI who have undergone abdominal surgery, postoperative gastroparesis can be a manifestation of pain. This may occur as the excessive sympathetic response from autonomic hyperreflexia inhibits distal antral activity. Thus, treatment of postoperative gastroparesis should focus on improved pain control to decrease excessive splanchnic sympathetic output and circulating norepinephrine. PMID- 17853663 TI - Infarction of the cervical spinal cord following multilevel transforaminal epidural steroid injection: case report and review of the literature. AB - BACKGROUND/OBJECTIVE: Transforaminal epidural steroid injection is a widely utilized nonsurgical strategy for the management of cervical radicular and axial pain. The technique has been shown to be efficacious in relieving the patients' symptoms. Although effective, there are a range of possible complications associated with this procedure. We report the case of a patient with an acute infarction of the cervical spinal cord after a multilevel transforaminal epidural steroid injection. METHODS: We performed a retrospective chart review of a single case. RESULTS: The patient suffered an acute brainstem and cervical spinal cord infarction despite the use of many techniques to minimize the occurrence of vascular injury during the procedure. The patient regained some function after medical and physical therapy. CONCLUSIONS: This complication, to our knowledge, has only been reported in the literature on 2 other occasions and serves as a reminder of the potentially devastating consequences of performing procedures in proximity to the nervous system. PMID- 17853665 TI - [Image of the month. Coronary fistula using non-invasive CT coronary imaging]. PMID- 17853664 TI - Prophylactic radical cystectomy for the management of keratinizing squamous metaplasia of the bladder in a man with tetraplegia. AB - BACKGROUND/OBJECTIVE: To report a case of keratinizing squamous metaplasia of the bladder treated with radical cystectomy. DESIGN: Case report and discussion of management options. METHODS: Keratinizing squamous metaplasia of the bladder is a rare entity that can result from chronic irritative stimuli involving the bladder. It is considered a premalignant condition associated with invasive squamous cell carcinoma. A case report is presented describing the diagnosis and management of keratinizing squamous metaplasia of the bladder in a tetraplegic man with a chronic indwelling urinary catheter. RESULTS: Radical cystectomy with an Indiana continent reservoir was performed after cystoscopy with biopsy confirmed keratinizing squamous metaplasia. Final pathology revealed focal erosion and diffuse keratinizing squamous metaplasia of the bladder with prostatic adenocarcinoma as an incidental finding. CONCLUSIONS: Patients with spinal cord injury who use indwelling catheters for bladder management are at higher risk of developing keratinizing squamous metaplasia. Surveillance for early detection of this entity is recommended. Prophylactic cystectomy is sometimes warranted; however, observation and frequent cystoscopic surveillance to identify potential malignant transformation can be an alternative strategy. An interdisciplinary approach is recommended before consideration of bladder resection. PMID- 17853666 TI - [Image of the month. Coronary artery to pulmonary artery fistula]. PMID- 17853667 TI - [Treatment of didelphys uterus with imperforated obstructed hemivagina]. AB - Didelphys uterus with imperforated obstructed hemivagina is a rare condition. Most often, it is diagnosed a few months after the menarche. Hematocolpos, hematometria and sometimes hematosalpinx are responsible for pelvic pain and dysmenorrhea. Symptoms can be delayed when a fistulisation from the hematocolpos to permeable contralateral vagina is present. Sometimes, diagnosis is not made before adulthood during an infection of the hematocolpos. Useful additional exams include pelvic ultrasound and, in some cases, MRI, which is the best exam to precisely describe the type of malformation. An ipsilateral agenesia of the kidney is always associated. Hysterography can usually demonstrate the fistulous courses. Treatment consists in a large resection of the vaginal septum in order to allow a permanent drainage of the hemiuterus. A laparoscopy should be performed to check for the presence of associated tubal or pelvic damage. PMID- 17853668 TI - [Rhabdomyolysis and hypothyroidism]. AB - We describe the case of a 29 year old patient who presented severe myalgias and asthenia for 3 months. First biological assessment revealed muscular lysis and raised transaminases. The following complementary screening showed major hypothyroidism with the presence of anti-microsomes antibodies, a carpian canal syndrome and a left ventricular systolic dysfunction. A diagnosis of hypothyroidic rhabdomyolysis consecutive to a Hashimoto disease was then mash. Patient was treated by hormonal thyroid substitution with a progressive improvement of muscular symptoms to complete recovery, and a concomitant normalization of cardiac and thyroid functions. PMID- 17853669 TI - [Catamenial pneumothorax : a case report]. AB - Catamenial pneumothorax is an unusual and rarely recognized entity that belongs to the thoracic endometriosis syndrome. The increase a number of published cases over the last years allows a more frequent diagnosis and understanding. We describe the story of a young woman with a recurrent right sided pneumothorax and discuss the different pathogenic mechanisms and current therapies. The rarity of the disease makes a prospective study very difficult. To this day, there is no consensus on a standardized therapeutic attitude. PMID- 17853670 TI - [Cutaneous manifestations of parvovirus B19 infection]. AB - The human parvovirus B19 is a small single-strand DNA virus with specific tropism for the membranous receptor P expressed on erythrocytes and endothelial cells. About 60 - 70 % of the adult population is parvovirus B19 seropositive. The contamination usually occurs through droplets from the nasopharyngeal airways. The major systemic infections present as episodes of aplastic anemia and development of hydrops fetalis. Arthropathies, encephalitis, or glomerulonephritis are less frequently encountered. This review focuses on its cutaneous manifestations including erythema infectiosum, and the purpuric syndromes whose principal manifestation is the papulo-purpuric gloves and socks syndrome. Several other cutaneous manifestations have been reported to be associated with the parvovirus B19 without however strong evidence. These include vasculitis, erythema nodosum, the lupus eythematosus-like syndrome, some vesiculo pustular eruptions, pityriasis lichenoides and scleroderma. PMID- 17853671 TI - [Pet turtle and septicemia: what is the relationship?]. AB - We report the case of a four months old girl who suffered from a Salmonella pomona's septicemia. The source of contamination was the pet turtle recently acquired by her parents. If the pet turtle-associated salmonellosis is still rare in our country, the high rate of carriage of this germ by these exotic pets and the potential severity of the human disease justify an epidemiological survey. People with immature or weakened immune systems should avoid contact with reptiles. PMID- 17853672 TI - [Ileum intussusception in an adult: a case report]. AB - Intussusception in adults is a rare cause of intestinal obstruction and is usually secondary to some lesion in the gastrointestinal tract. We report a case of intestinal obstruction due to ileo-ileal intussusception, an inflammatory fibroid polyp formed the leading edge of the intussusceptum, which is a rare polypoidal lesion of the gastrointestinal tract. PMID- 17853673 TI - [Sexual abuse: from the young victims' point of view...]. AB - A child subjected to sexual abuse will react differently than an adult would. We will come back to the reasons why. In addition to these characteristics inherent to the child, many other factors make the handling of the situation difficult and unusual. The consequences of child abuse, whether visible or not, do indeed unquestionably alter the child's cognitive schemes and the relationships he will built in the future. Do these factors, inherent to the child or to the abusive relationship, always influence the immediate outcome, the followup and the psychological future of these young victims of sexual abuse? PMID- 17853674 TI - [Primitive pleural hydatid cyst: case report]. AB - Even in endemic countries, the primitive pleural hydatid cyst is exceptionnal and it's very difficult to distinguish from other pleural and parietal cystic masses all the more the immunologic tests are negative. We report the case of a primitive pleural hydatid cyst diagnosed in 43 years old man. Throug this case, imaging features are emphasized. PMID- 17853675 TI - [Historical cohort study of delivery in women of forty years of age and older]. AB - In a recent study at the Yaounde-Cameroon University Teaching Hospital, we found that delivery at extreme ages of reproductive health was associated with increased foetal and maternal risks. However we were not able to evaluate the impact of advanced age on exposure do different risks observed. The purpose of this study was to test the hypothesis that deliveries of women aged 40 years and above were associated with increased risk. Data collection was retrospective from delivery room registers at the Yaounde University Teaching Hospital Between 01/01/1991 - 31/12/2000. The deliveries of 180 women in their forties were compared with those of 532 women in their twenties. The software EPI Info 6 and SPSS were used in analysis. At unvaried analysis, the risk of delivery by caesarean section for women in their forties (16.1%) was significantly high compared to women in their twenties (10.0%), (HR: 1.7; 95% CI: 1.1-2.8; p = 0.027). After adjustment for different factors associated with the occurrence of delivery by caesarean section, its risk for women aged 40 and above remained significantly increased (HR: 1.7; 95% CI: 1.0-2.9; p = 0.039). Similar observation was found for stillbirth with 11.7% by women aged 40 and above compared to 5.8% by women in their twenties (HR: 2.1; 95% CI: 1.1-3.9; p = 0.011). After adjustment for different factors associated with mortinatality, its occurrence remained significantly increased at age 40 and above (HR: 1.9; 95% CI: 1.1-3.6; p = 0.032). Women aged 40 years and above had an increased risk of stillbirth and delivery by caesarean section than those in their twenties. Studies are needed to establish the exact causes of these risks and evaluate management options in these women. PMID- 17853676 TI - [Ground-glass opacity and mixed pulmonary nodules: a new computed tomography semiology of the pulmonary adenocarcinoma]. AB - Recently a new computed tomography semiology of the pulmonary adenocarcinoma was highlighted. Studies on ground-glass nodule and on mixed nodule showed the relation between these radiological images and the different anatomopathological forms of lung adenocarcinoma. Ground-glass opacity can correspond to precancerous lesions and morphological characteristics of nodules are correlated with the prognosis. The presence of spiculation, pleural retraction and air bronchogram is significantly more important in neoplasic lesions. The presence or the apparition of a solid component inside the nodule or the presence of indentation is highly suggestive of adenocarcinoma. A lesion smaller than 20 mm and persistant after 1 month must be, either followed up, or removed by a limited surgical resection. Lesions larger than 20 mm or associated with a solid component must be treated by conventional surgery. PMID- 17853677 TI - [Beriberi]. AB - We discuss the case of a 49 year old man who was admitted to the emergency department with acute heart failure. He suffered from severe alcoholism and malnutrition. His heart failure was of the high output type and the diagnosis beriberi, a disease caused by thiamine (vitamin B1) deficiency. The treatment consisted of intravenous administration of thiamine. The clinical response was spectacular with normalization of cardiac function within a few hours. PMID- 17853678 TI - When worry hijacks the brain. PMID- 17853679 TI - The science of addiction. PMID- 17853680 TI - Young survivors. What science can learn from the first generation of kids to beat childhood cancer. PMID- 17853681 TI - Painting tumors. A new technique coats cancers for easy identification. PMID- 17853682 TI - A patient you never saw can sue you. PMID- 17853683 TI - Give patients their visit notes. PMID- 17853684 TI - EMI: keep your equipment humming. PMID- 17853685 TI - Is P4P getting tougher? PMID- 17853686 TI - Now I understand the terror. PMID- 17853687 TI - Retire in your 50s--these doctors will! PMID- 17853688 TI - [Apoptosis-modulating effect of prostaglandin E2 in coelomocytes of holothurian Eupentacta fraudatrix depends on the cell antioxidant enzyme status]. AB - The effects of prostaglandin PGE2 on apoptosis and antioxidant enzyme activities were studied in two coelomocyte fractions of holothurian Eupentacta fraudatrix in vitro and in vivo. PGE2 (10(-8) - 10(-6) M) modulated apoptosis in a time- and concentration-dependent manner in both fractions studied in vitro. In vivo, PGE2 induced apoptosis at concentrations of 0.1-1 microg/g in the fraction enriched with morula-like cells. Phagocytes were more sensitive to the regulating effect of PGE2. In this fraction, PGE2 induced apoptosis at concentrations from 0.01 to 1 microg/g, while PGE2 at 10 microg/g demonstrated an antiapoptotic effect. In all experiments, apoptosis development was accompanied by a disbalance of the antioxidant enzyme system, primarily, decreased catalase activity. PMID- 17853689 TI - [Protein inhibitors of fibrin stabilizing factor FXIII]. AB - The ability of cysteine proteinase inhibitors (CPIs) isolated from tubers of potato (Solanum tuberosum) to suppress transpeptidase activity of fibrin stabilizing factor (FXIIIa) through the direct effect on the essential SH group of the enzyme active site has been studied. The formation of fibrin clots soluble in 5 M urea and 2% acetic acid as well as spectrophotometric turbidity analysis of the stabilization and resistance of fibrin clots formed in the presence of FXIIIa and CPIs from potato tubers to plasmin, and electrophoresis of reduced fibrin samples indicate the decrease or absence of covalent crosslinking of fibrin chains. In addition, CPIs added to the substrate proved to decelerate fibrinogen polymerization almost twice relative to control. It is concluded that natural CPIs can both take part in the regulation of FXIIIa transpeptidase activity in vitro and modify the substrate. PMID- 17853690 TI - [A method for cultivation of microorganisms oxidizing iron and manganese in bottom sediments of Lake Baikal]. AB - Methods for cultivation of microorganisms oxidizing iron and manganese in bottom sediments of Lake Baikal were tested. Bacteria were grown on selective media with a characteristic accumulation of metal oxides. The morphology and developmental patterns of the isolated microbial group were studied. The studied sediment core was used to isolate 42 strains of bacteria oxidizing iron and manganese. The cultivated bacteria were confined to the upper sediment layers (down to 11 cm) and their abundance depended on sediment type and redox conditions. PMID- 17853691 TI - [Actinomycete growth in conditions of low moisture]. AB - Actinomycete communities demonstrated a replacement of the generic composition in time as a function of soil moisture. Representatives of the genera Streptomyces, Micromonospora, Actinomadura, Saccharopolyspora, and Microbispora were repeatedly isolated from soil under different moisture conditions (field capacity, maximum molecular capacity, and maximum adsorption capacity). Representatives of some rare genera (Thermomonospora and Kibdelosporangium) were isolated from soil with low moisture levels inhibiting growth of more hydrophilic actinomycetes and bacteria. Spores of some actinomycetes could grow at low relative air humidity (RH) (50 and 67%). The complete growth cycle of all actinomycetes starting from spore germination to sporulation was observed only at RH of 98%. PMID- 17853692 TI - [Disturbed structure and function of chloroplasts during blocked biosynthesis of 5'-aminolevulinic acid in the light]. AB - Xantha-702 mutant of cotton (Gossypium hirsutum L.) proved to have blocked synthesis of 5'-aminolevulinic acid in the light. Accordingly, mutant leaves accumulated 2-5% chlorophyll of baseline. Mutant plants demonstrated disturbed production of pigment-protein complexes of photosystems I (PSI) and II (PSII) and generation of the chloroplast membrane system blocked at the early stages, largely, at the stages of vesicles and single short thylakoid. The functional activity of the PSI and PSII reaction centers was close to zero. Only the chlorophyll a/b light-harvesting complexes of PSI and PSII with the chlorophyll fluorescence peaks at 728 and 681 nm, respectively, were produced in the xantha 702 mutant. We propose that the genetic block of 5-aminolevunilic acid biosynthesis in the light in the xantha-702 mutant disturbs the formation and activity of the complexes of the reaction centers of PS-I and PS-II and inhibits the development of the whole membrane system of chloroplasts. PMID- 17853693 TI - [Feeding rate of sibling vole Microtus rossiaemeridionalis and Mandarin vole Lasiopodomys mandarinus]. AB - Consumption of food of different nutritive value by sibling vole Microtus rossiaemeridionalis and Mandarin vole Lasiopodomys mandarinus as a function of housing conditions--in cages or enclosures--was comparatively studied. Experimental groups included 8-14 adult non-reproducing animals of both sexes kept one per cage or enclosure. The rate of food consumption and digestibility were studied by standard methods and the obtained data were statistically analyzed using Statistica 6.0. Significant differences in the rate of food consumption by mandarin voles housed under different conditions as well as in the consumption and digestibility of food of different biochemical composition in both vole species have been revealed. PMID- 17853694 TI - [Correction of changes induced by toluene in the cortical and subcortical structures of albino rat brain]. AB - The number and weight of cells in the cortical and subcortical structures of the cerebral and cerebellar motor system in albino rats after a long-term exposure to toluene. Toluene intoxication proved to kill projection neurons and interneurons in the sensorimotor cortex, ventrolateral thalamic nucleus, caudate nucleus, pallidum, red nucleus, and inferior olivary complex. The decreased number of cerebellar cells was mediated by atrophic changes as indicated by the decrease in the area and dry weight of Purkinje cells. The addition of plaferon LB to the diet attenuated the cytotoxic effect of toluene. PMID- 17853695 TI - [Nitric oxide is involved in the protective effects of short-term adaptaion to hypoxia in the course of stress-induced disorders in Krushinsky-Molodkina rats]. AB - A possible involvement of nitric oxide in the protective effect of short-term adaptation of Krushinsky-Molodkina rats to mild hypoxia simulating 5000 m above sea level was studied. Nitric oxide proved to have a considerable protective effect on stress-induced disorders in Krushinsky-Molodkina rats as demonstrated using NO-synthase inhibitors and NO monitoring by electron spin resonance under different experimental conditions. PMID- 17853696 TI - [The role of visceral receptors in the mechanisms of neuroimmune interactions in mammalian small intestine]. AB - Exogenous administration of mast cell degranulation products into blood as well as their endogenous release induced by compound 48/80 or repeated egg albumin administration to sensitized rats proved to increase activity of mesenteric afferent nerve fibers in the small intestine. In addition, the primary contact with a foreign protein triggered a cascade of chemical processes mobilizing antioxidant systems and increasing nitric oxide production in the small intestinal tissues. Interleukin-1beta or Escherichia coli lipopolysaccharide injections also had a long-term stimulating effect on intestinal receptors. Indometacin inhibited the effects induced by the bacterial endotoxin and interleukin-1beta. The obtained data suggest that small intestinal interoceptors can monitor chemical environment and modulate body's responses to foreign antigens. Interleukins-1beta acts as a signal transmitter between immune cells and interoceptors, which is mediated by the production of secondary signal substances, in particular, prostaglandin-2 and histamine. PMID- 17853697 TI - [Definition of unit internal (physiological) time]. AB - We provide a definition of the unit internal (physiological) time based on metabolism. If q(t) is specific rate of metabolism, i.e. the amount of energy (oxygen) consumed by unit of active mass per physical time unit, the unit of physiological time tau(t) is defined as physical time, during which unit of active mass consumes one unit of energy: tau(t) = 1/q(t). The dimension of unit physiological time is the same as that of unit physical time and its value depends on q(t). Therefore, the unit physiological time tau(t) is a variable value, while the internal time is unequal relative to the physical time. The more internal time units tau, i.e., elementary acts of energy consumption, fit in the unit physical time t, the longer is the unit physical time for the unit active mass relative to the internal time unit, i.e., the physical time is seemingly slowed down. And, on the contrary, the less elementary acts of energy consumption take place during unit physical time, the shorter seems unit t, i.e. physical time is seemingly accelerated. Unequal course of the internal time is determined by the curve of specific metabolism q(t) during the life under specific conditions and, hence, internal time is individual. It has been questioned that the total (during lifetime) specific metabolism, often called Rubner constant, can serve as specie specific characteristic. PMID- 17853698 TI - [Plant communities of environmental interfaces as a problem of ecology and biogeography]. AB - A variety of problems concerning the ecology, distribution, and classification of plant communities of environmental interfaces have been considered. PMID- 17853699 TI - [Oxidoreductase activity of peat soils as an indicator of the degree of biochemical transformation of drained and forested bogs in west Siberia]. AB - Multivariate analysis unambiguously demonstrated the differentiation of oxidoreductase activity (catalase, peroxidase, and dehydrogenase) in peat soils after a 20-25-year period of bog drainage and afforestation. The enzyme activity depended on the drainage depth. A statistical model has been developed to predict the degree of humification of peat organic matter from peroxidase activity and moisture of drained soils. Soil peroxidase activity can be an important indicator of the degree of biochemical transformation of drained and forested bogs. PMID- 17853700 TI - [Ultrastructure of diatom Synedra acus subsp. radians as revealed by transmission electron microscopy after mild silica dissolution]. AB - A diatom Synedra acus subsp. radians (Kutz.) Skabitsch. has been studied by transmission electron microscopy. Examination of ultrathin sections demonstrated that silica dissolution in ammonium fluoride pH 5 under mild conditions leaves the key ultrastructural elements intact. The ultrastructure and arrangement of the cell organelles was studied during ontogeny. Silicalemma-surrounded silica deposition vesicles (SDVs) with maturating daughter valves and forming girdle bands have been identified. This method of SDV visualization offers considerable advantages over the standard approach without silica dissolution. PMID- 17853701 TI - [Ultrastructural changes in somatosensory cortex of albino rats during space flight]. AB - For the first time, mammalian brain has been studied during space flight aboard NASA orbital laboratory Spacelab-2. The main ultrastructural differences in the somatosensory cortex of the brain fixed under microgravity conditions and after landing include an increased number of degenerating presynaptic axon terminals after landing. Apparently, this is due to a sharp increase in afferent impulsation in the cortex during and after landing. PMID- 17853702 TI - [Metabolic changes of lymphocytes and neoplastic cells in mice with Ehrlich ascites carcinoma during tumor growth]. AB - Changes in the activities of NAD+- and NADP-dependent dehydrogenases of lymphocytes and tumor cells were studied in mice with Ehrlich ascites carcinoma, as well as changes in the concentrations of oxaloacetate, lactate, and NAD+ in the course of tumor growth. During the major period of tumor growth, conditions are produced in the lymphocytes for increased intensity of aerobic reactions directed at energy reproduction combined with a somewhat decreased intensity of synthetic processes. In the tumor cells, conditions predominantly arise for intensification of plastic metabolic reactions and reactions related to anaerobic energy reproduction. PMID- 17853703 TI - [Sigmund Freud (1856-1939)--contributions to medicine]. PMID- 17853704 TI - [Mode of delivery and neurosonographic findings in premature infants]. AB - INTRODUCTION: Fetal and preterm infant brain is especially vulnerable to hemorrhagic and ischemic damage at the end of the second and at the beginning of the third trimester. This is due to vascular, cellular and anatomic characteristics of the brain during development. In premature babies, there is a physiological instability and limited autoregulation of cerebral circulation. Hemorrhagic and ischemic damages often occur together, though pathophysiological processes leading to lesions are different. MATERIAL AND METHODS: The paper deals with a detailed analysis of 860 ultrasound brain scans of prematurely born children. The examinations were performed at the Ultrasound Department of the Institute of Child and Youth Health Care in Novi Sad. 707 vaginally born premature infants and 153 premature infants born by Cesarean section were examined The bleeding was graded according to the Papile classification. RESULTS AND DISCUSSION: Out of 384 children with diagnosed grade I hemorrhage, 75 premature infants (19.5%) were born by Cesarean section. In the group of children with grade II hemorrhage, operative deliveries account for 14.7%. From the total of 85 children with grade III hemorrhage, (intraventricular bleeding with chamber dilatation), only 6 premature infints were born by Cesarean section (7%). Intra parenchymal bleeding was diagnosed in a very small number of premature infants: 0.32% of all diagnosed hemorrhages were grade IV hemorrhages. In this group there were no children born by Cesarean section. The increase of hemorrhage grade is accompanied by a greater rate of pelvic presentation and manual assistance by Bracht. There were 240 prematurely born children with no echosonographicallY diagnosed hemorrhage, 38% of all examined premature infants. From this number, 13.3% of neonates were born by Cesarean section. CONCLUSION: In the etiology of neonatal intracranial hemorrhage, especially prematurely born ones, apart from the trauma, which plays a major role, other factors are also important, above all fetal distress, perinatal hypoxia and junctional immaturity of all organs. PMID- 17853705 TI - Nosocomial infections in patients with acute central nervous system infections. AB - Due to current increase in the rate of nosocomial infections, our objective was to examine the frequency, risk factors, clinical presentation and etiology of nosocomial infections in patients with central nervous system infections. 2246 patients with central nervous system infections, treated in the intensive care units of the Institute of Infectious and Tropical Diseases, Clinical Center of Serbia in Belgrade and at the Department of Infectious Diseases of the Clinical Hospital Center Kragujevac, were included in this retrospective and prospective study. Clinical manifestations of nosocomial infections were registered in 180 (12.7%) patients. Direct risk factors for nosocomial infections were: venous lines, urinary catheter, length of stay over 20 days, inhibitors of gastric secretion, consciousness disorders and coma, endotracheal intubation, tracheotomy and controlled ventilation for 5 days or more. The most frequent clinical presentations of nosocomial infections were: tract urinary infections, bacteriemia/sepsis and nosocomial pneumonia. Significantly higher frequency of death outcomes was registered in patients with nosocomial infections. PMID- 17853706 TI - [Characteristics of galanin and vasoactive intestinal peptide immunoreactivity in the rat amygdala complex]. AB - INTRODUCTION: Morphological features and morphometric parameters of galanin (GAL) and vasoactive intestinal peptide (VIP) immunoreactive neurons and neuronal fibres were studied in all nuclei of adult male rat amygdala. MATERIAL AND METHODS: After perfusion and fixation, rat brains were immunohistochemically stained with antibodies against GAL and VIP and then visualized by avidin-biotin peroxidase complex. RESULTS AND DISCUSSION: The greatest number of galanin immunoreactive neurons were identified in the medial part of the central nucleus and in the dorsal part of the medial nucleus. In the first case, most neurons were bipolar (37%), and in the second, they were ovoid (45%). GAL-immunoreactive fibers were identified in the medial nucleus, "bed nucleus" of the accessory olfactory tract, fiontal cortical nucleus, amygdalo-hippocampal area and basolateral nucleus. VIP-immunoreactive neurons were diffusely distributed in more nuclei than the previous, mostly in the lateral, basolateral, and basomedial nucleus. They were mostly ovoid (40%). VIP-immunoreactive fibers were observed in the lateral part oJ'the central nucleus, while long and radially oriented fibers were present in the frontal and dorsal cortical nucleus. CONCLUSION: By distribution analysis of GAL and VIP immunoreactive neurons and fibers, and according to literature data, it can be assumed that the medial part of the central nucleus receives VIP fibers from other parts of the amygdaloid body, and then sends GAL fibers to the medial nucleus. PMID- 17853707 TI - [The use of combined hyperbaric oxygenation and erythropoietin in the treatment of cardiac insufficiency]. AB - INTRODUCTION: The aim of this research is to evaluate therapy efficiacy of hyperbaric oxgenation (HBO) with regenerative effects on human tissues and erythropoietin, as a nonspecific growth factor. MATERIAL AND METHODS: This study included a group of 9 patients with echocardiographically diagnosed cardiac insufficiency with ejection firaction (EF%) under 60%. HBO was used according to the protocol for patients with severe cardiac insufficiency (a total of 15 treatments). All patients also received subcutaneous erythropoietin, 2000 i.v., every other day. Control echocardiography was done 30-45 days after they finished their treatments. RESULTS: The average ejection fraction before treatment was 46%. After treatment, the average EF% was 57%, so it increased by 11%. All patients felt subjectively better, with improved capacity to physical efforts. DISCUSSION AND CONCLUSION: Ejection fraction of 30-40% is an indication for hyperbaric oxygenation therapy. The decision about the treatment is made by the physician based on his experience, general condition of the patient, frequency and severity of hypoxic episodes. If EF% is 30% or below, HBO is not recommended, because antioxidative defense mechanisms are exhausted under hyypoxia and the balance of the organism should not be changed. An increase in average EF% by 11% demonstrates that combined use of HBO and Erythropoietin gives good results. PMID- 17853708 TI - [Metastases of unknown origin--principles of diagnosis and treatment]. AB - DEFINITION: Cancer of unknown primary (CUP) origin refers to patients who present with histologicaly confirmed metastatic cancer in whom a detailed medical history, complete physical examination, including pelvic and rectal examination, full blood count and biochemistry, urinalysis and stool occult blood testing, hisinpathological review oJ biopsy speimens with the use of immunohistochemistry, chest radiography, computed tomography of the abdomen and pelvis, and in certain cases mammography, fail to identify the primary site. EPIDEMIOLOGY OF CUP: The cancer of unknown primary accounts for 3%-5% of all human cancers. DIAGNOSIS OF CUP: The standard diagnostic procedure for the majority of patients includes histopathologic review of biopsy specimens with the use of immunoltistochemistry, chest radiography, computed tomography of the abdomen and pelvis, and in certain cases mamography, fail to identify the abdomen and pelvis. The four common histologic diagnoses are: adenocarcinoma (70%), poorly differentiated carcinoma (20%), squamous carcinoma (10%), and poorly differentiated neoplasms (5%). PROGNOSIS OF CUP: The prognosis for most patients with unknown primary tumors is poor, with survival often less than 6 months from diagnosis. THERAPY OF CUP: Based on clinical and pathologic features, approximately 40% of patients can be categorized within subsets for which specific treatment has been defined. Empiric therapy is an option for the remaining 60% of patients. CONCLUSION: Metastatic tumors of unknown origin have a unique clinical presentation due to a specific biology. Insight into the molecular biology of unknown primary tumors will be essential for the development of more effective treatments. PMID- 17853709 TI - [Lipoprotein(a): a link between thrombogenesis and atherogenesis]. AB - INTRODUCTION: It is well known that numerous mechanisms of thrombogenesis can participate in every stage of atherosclerotic disease. The discovery of Lp(a) lipoprotein and its structural similarity with plasminogen suggests another pathogenic link between atherogenesis and thrombogenesis. SOME CHARACTERISTICS OF LP(A) LIPOPROTEIN: This lipoprotein is present in the whole human population in a wide range of plasma concentrations. It has numerous different isoforms. Its synthesis occurs in the liver, but it is practically metabolically independent from other lipoproteins. Today, Lp(a) lipoprotein is considered to be an independent risk factor for heart and brain ischemic disease. FIBRINOLYTIC MECHANISMS: The primary role of the fibrinolytic mechanism is to prevent thrombus Jormation during circulation and to remove already formed ones. Plasmin has a central role in this process, due to the inactive proenzyme plasminogen. Its basic activators are tissue-type plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA). The most important inhibitors of plasminogen are alpha2-antiplasmin and plasminogen activator inhibitors 1 and 2 (PA-1 and PAI-2). Structural similarity of Lp(a) and plasminogen The apo(a) and plasminogen genes are very closely linked on the long arm of chromosome 6. Because of that they are structuraly very similar and they have a cross immunological reactivity. Their common elements are so-called "kringle" structures. The key difference in structure of Lp(a) and plasminogen is replacement of Arg with Ser at position 560. This prevents splitting of apo(a) by plasminogen activators. LP(A) AND FIBRINOLYSIS: Lp(a) lipoprotein inhibits activation of plasminogen by streptokinase. It is also a competitive inhibitor of plasminogen for its binding to plasminogen receptors. Furthermore, it successfully achieves competitive inhibition of plasminogen for binding to tetranectin and thrombospondin. Also, Lp(a) inhibits activation of transforming growth factor alpha (TGF-alpha). It positively correlates with PAI-1 and it is assumed that it promotes release of tissue factor pathway inhibitor (17FPI) from endothelial cell surfaces. CONCLUSION: In regulation of the hemostatic system via apolipoprotein(a) antifibrinolytic effects, Lp(a) lipoprotein ojfers a molecular solution to the link between thrombogenesis and atherogenesis. PMID- 17853710 TI - [Peripiheral blood hematopoietic stem cells--biology, apheresis collection and cryopreservation]. AB - INTRODUCTION: ilematopoiesis is a continuous, dynamic and highly complex process resulting in production of various mature blood cells from a small population of pluripotent stem and progenitor cells through diverse proliferative and differentiative events. Numerous studies have demonstrated that a complex network of interactive cytokines regulates the survival, maturation, and proliferation of hematopoietic stem and progenitor cells. APPLICATION OF CELL-MEDIATED THERAPY: Massive application of different cell-mediated therapeutic methods has resulted in an increased need for both specific IISPCs and operating procedures providing minimal cell damage during collection, processing and storage in a liquid or fiozen state. Therefore, the basic aim of cell harvesting, selection, as well as cryopreservation is to minimize cell damage during these procedures. HSPCs are cells which exhibit extensive self-renewal and proliferative capacity, associated with the capacity to differentiate into all blood cells and other cell lineages (plasticity of HSPC). Thanks to these properties, stem cells can provide complete and permanent restoration of hematopoiesis, which is the basis for clinical employment of HSPC transplantation. In addition, totipotent stem cells can be used for the so called "cell-therapy" in different clinical settings (e.g. myocardial regeneration after acute infarction). CONCLUSION: Despite the fact that HSPC transplantation is already in routine use, some questions related to the optimal blood progenitor/cell collection, selection, storage and clinical use are still unresolved. Therefore, this review only briefly discusses the therapeutic use of HSPCs in different clinical areas and focuses on the recommendations, as well as the specific transfusion policies related to HSPC collection, processing, and cryopreservation with an emphasis on quality control. PMID- 17853711 TI - [Surgical techniques and outcomes in the treatment of malignant tongue base tumors]. AB - INTRODUCTION: Prognosis of patients with malignant tongue base tumors is poor. Survival is low, in spite of different treatment modalities. Most patients seek treatment too late, when their disease has already progressed to stage III or IV. The aim of this investigation was to compare different treatment modalities in patients with malignant tongue base tumors. MATERIAL AND METHODS: We have analyzed a total of 82 patients (72 men and 6 women) treated at the ENT Clinic, Clinical Center Novi Sad, between 1992 and 2004. The average age of our patients was 59 years. In regard to lifestyle habits, out of 82 patients, 67 were smokers and 57 were alcohol users (16 of the latter were treated alcoholics). The majority (54/82) of patients were both smokers and alcohol users. RESULTS: There were 6% of patients (5/82) with stage I disease, 15% ofJ patients (12/82) with stage 11, 24% of patients (20/82) with stage III and 55% of patient (45/82) with stage IV disease. Planocellular cancer was diagnosed in 79/82 patients, and the remaining (3182) had transitional cell carcinoma. Surgical treatment alone was performed in 17 patients, seven were treated with radiation only, and nine only with chemotherapy. Combined surgical and radiation therapy was performed in 28 patients, and 5 were treated with all three. Ten patients were not treated with any therapy. Tongue base resection only was performed in 12 patients, tongue base resection with epiglottectomy in 20, tongue base resection with supraglottic laryngectomy in 13 and tongue base resection with total laryngectomy in 5 patients. In radiation only cases, 25% of patients survived 20 months, whereas in surger) only cases, 25% of patients survived 27 months. Five-year survival after combined surgical and radiation therapy was 35% CONCLUSION: Development of tongue base carcinoma is strongly associated with alcohol and tobacco consumption. Survival is low, despite various treatment modalities. However, combined therapy is the therapy of choice in cases with tongue base carcinoma. PMID- 17853712 TI - Endoscopic carpal tunnel release using the modified Chow's extrabursal dual portal technique: clinical results of 640 patients. AB - During a 4-year period, a total of 784 wrists of 640 patients were treated using a modified Chow's extrabursal dual portal endoscopic technique. All surgeries were performed under local anesthesia. A 1-cm incision was marked 1-2 cm proximal to the distal wrist crease, in the midline, ulnar to the palmaris longus. A distal portal was established along a line bisecting an angle created by the intersection of the ulnar border of the abducted thumb and the third web space. An obturator and cannula assembly were inserted under the portal, and three blades were used to cut under endoscopic vision. Subjective results showed that 706 hands (90%) had a reduction in the severity of pain after carpal tunnel release, 706 hands (90%) had a reduction in the severity of paresthesia and 729 hands (93%) had a reduction in the severity of numbness. Nocturnal pain and paresthesia were relieved in 745 cases (95%). Compared with the conventional open carpal tunnel release, less postoperative pain and faster recovery have been reported following endoscopic carpal tunnel release. This study suggests that extrabursal dual portal technique is a safe and reliable treatment option for carpal tunnel syndrome with a high success rate. PMID- 17853713 TI - [Causes of sudden cardiac death in athletes]. AB - INTRODUCTION: Sudden cardiac death in athletes is a growing problem, despite the huge existing knowledge in medicine and sports. EFFECTS OF VIGOROUS PHYSICAL ACTIVITY: In response to vigorous physical activity, the body undergoes profound morphologic and functional changes. These changes are usually healthy, but sometimes may gravitate to some cardiac diseases. But still, most saudden cardiac deaths are due to previous unknown diseases. CAUSES OF SUDDEN CARDIAC DEATH: The most common cause of sudden cardiac death in athletes is hypertrophic cardiomyopathy. Other reasons are congenital coronary artery anomalies, nivocarditis, dilatative cardiomyopathy, arrhythmogenic cardiomyopathy of the right ventricle, sarcoidosis, mitral valve prolapse, aortic valve stenosis, atherosclerosis, long QT syndrome, and blunt impact to the chest. CONCLUSION: Bearing in mind the above mentioned, more frequent physical examinations of athletes are recommended. PMID- 17853714 TI - [Ultrasound screening program for chromosomal abnormalities--the first 2000 women]. AB - INTRODUCTION: Screening for chromosomal abnormalities identifies the group of women at higher risk for having a fetus with chromosomal abnormalities and the need for fetal karyotyping. In order to provide high quality screening, strict criteria Jbo certification of operators are introduced, issued by the Fetal Medicine Foundation (FMF), which enables annual external control of results. The aim of this study was to review the results of five-year prenatal screening for chromosomal abnormalities in Novi Sad, Serbia. MATERIAL AND METHODS: Ultrasound screening at 11-15 weeks gestation was performed, assessing fetal morphology, crownr-rump length and nuchal translucency (NT) according to the FMF guidelines. Risk for chromosomal abnormalities included the initial risk, based on maternal age, gestational age and anamnestic data, and corrected risk, which took into account the initial risk and the value of the nuchal translucency. The corrected risk was issued by the computer program issued by the FMF. RESULTS: During the period 1999-2004, 4580 pregnant women were scanned. The risk for chromosomal abnormality was calculated using the FMF program in 2245 cases and the outcome was known in 1406 cases. The majority ojf women were between 25 and 29 years of age (37%), and 12% were older than 35 years. NT was below the median in 43% of cases and above in 57%, 3.7% of cases were above the 95th centile. 89% of women iwere younger than 35, and the risk was reduced in 97% of cases. There were three false negative cases. In 3% of women from this group the risk was increased, out cf which there were five cases of trisomy 21 and two terminations were done due to major anomalies. In the group of women over 35 years, the risk was reduced in 95% of cases and in all of them but two the karyotype was normal. In one of the two cases there was a large omphalocele and the karyotype was trisomy 18, and in the other fetus appeared normal, but after amniocentesis due to maternal anxiety, karyotype was 47, XYY. In 5% of women at higher risk there was one trisomy 21, bilateral multicystic kidneys were fund in one case as well as one hydrocephalus. CONCLUSION: Combined screening by maternal age and nuchal translucency is superior to screening by maternal age only--(sensitivity 66% vs. 20%, false postive results 3% vs. 15%, area under ROC 0.90 vs. 0.69). PMID- 17853715 TI - [Central venous catheter-related infections: risk factors and effects of glycopeptide antibiotics]. AB - INTRODUCTION: Central venous catheters (CVC) are used in the treatment of critically ill patients. Indications for placement of CVCs include hemodynamic monitoring, administration of intravenous fluids, medications and total parenteral nutrition. MATERIAL AND METHODS: We investigated risk factors and effects of glycopeptide antibiotics on the development of central venous catheter related injections in 300 patients treated in intensive care units. A semiquntitative culture technique was used. The investigation included: age, diagnosis on admission, catheter insertion site, catheter duration, the first or next catheter and using of glycopeptide drugs. RESULTS: 91 catheters (30.3%) were colonised, catheter-related infection was found in 50 catheters (16.7%). Infections were more frequent in catheters inserted through the internal jugular vein than in subclavian venous catheters, they were also more frequent if duration of catheterization was longer than seven days, but less frequent in patients who received glycopeptide antibiotics. The isolated microorganism was Staphylococcus aureus. Discussion According to the literature, a number of catheter-related risk factors for infections include: insertion site, type of catheter, the number of manipulations, inadequat asepsis, lumen number, type of antiseptic. The relative importance of one risk factor over another is difficult to assess, given that studies have no priority report. CONCLUSION: The duration of catheterization and the insertion site were the most frequent risk factors for infection. The use of glycopeptide antibiotics during catheterization has protective effects. PMID- 17853716 TI - [Fever of unknown origin--a case report of brucellar discitis]. AB - INTRODUCTION: Febrile episodes of unknown origin lasting for two weeks require detailed investigation by various medical specialists. Fever of unknown origin is most commonly caused by infections, malignancy, colagenosis and in 5-10% of cases, despite detailed diagnostic assessmnet, the cause remains unknown. In cases of fever of unknown origin, the diagnostic procedures are difficult and complex. CASE REPORT: This is a case report of brucellar discitis in a female patient treated at the Clinic of Endocrinology, Diabetes and Metabolic Diseases with a diagnosis of fever of unknown origin. Her laboratory findings revealed high erythrocyte sedimentation rate, anemia and high gamma globulin fractions. The patient underwent radiology examination and a suspicion of infection was defined, which was later confirmed by additional tests. CONCLUSION: Despite the fact that the diagnostic investigations of patients with fever of unknown origin are complex and time consuming, detection of the cause is of utmost importance and it is a prerequisite for successful therapy. PMID- 17853717 TI - [Abdominal aortic aneurysm--rupture of the anterior wall]. AB - INTRODUCTION: An aneurysm is a focal dilatation of an artery (aorta), involving an increase in diameter of at least 50% as compared to the expected normal diameter (over 3 cm). Abdominal aortic aneurysms (AAA) cause thousands of deaths every year, many of which can be prevented with timely diagnosis and treatment. AAA can be asymptomatic for many years, but in one third of patients whose aneurysm ruptured, the mortality rate is 90%. In the past, palpation of the abdomen was the preferred method for identifyng AAA. However, diagnostic imaging techniques, such as ultrasonography and computed tomography are more accurate and offer opportunities for early detection of AAA. CASE REPORT: This paper is a case report of an 83-year-old female patient. She was admitted due to severe pain in the abdomen. We already knew about the AAA (from her medical history). After using all available diagnostic procedures, rupture or disection of the AAA were not comfirmed. The patient underwent emergency surgery. During the operation, rupture of the anterior wall of the aneurysm was found. The anterior wall was filled with parietal thrombus, which hermetically closed the perforation. The patient was successfully operated and recovered. CONCLUSION: The aim of this case report was to point out that our diagnostic procedures failed to confirm the rupture of AAA. We decided to apply surgical treatment, based on medical experience, clinical findings, ultrasonography and computed tomography and during operation rupture of AAA was confirmed Patients with an already diagnosed AAA, or patients with clinical picture of rupture or dissection, are in urgent need for surgery, no matter what diagnostic tools are being used. PMID- 17853718 TI - [Acute appendicitis in a femoral hernia]. AB - INTRODUCTION: Acute appendicitis in a femoral hernia is an uncommon condition that can be serious. Complications are more frequent if the diagnosis is delayed and surgery is not performed on time. CASE REPORT: We present a 71-year-old man with a painful swollen mass. The patient presented with fatigue and loss of appetite, while body temperature was normal. The abdomen was not painful, and peristaltic was normal. All laboratory findings were normal. After anamnesis and physical examination, the presumed diagnosis was incarcerated femoral hernia and the patient was sent to the operating room. Intraoperative findings revealed an incarcerated femoral hernia within a phlegmonous inflammated appendix. Appendectomy and McVay hernioplastics were done. The postoperative course was without complications. CONCLUSION: It is very important to bear in mind that right femoral hernia with signs of incarceration and inflammation may contain an acutely inflamed appendix. Delayed diagnosis and misdiagnosis cause greater morbidity and mortality. PMID- 17853719 TI - [The frequency of pathological ultrasonographic findings of the gallbladder in patients with infectious diseases]. AB - INTRODUCTION: The objective of our study was to establish, through retrospective analysis of sonographic findings obtained by portable ultrasound devices, the frequency of pathological findings of the gallbladder and common bile duct in a randomized group of patients with infectious diseases. MATERIAL AND METHODS: During five years (January 1, 2000 - December 31, 2004), gallbladder and common bile duct were examined by ultrasonography in 2691 adult patients (1440 males and 1251 females), mean age 48 +/- 17 years, ranging from 17 to 92 years at the Institute of Infectious and Tropical Diseases in Belgrade. The examination included the measurement of size and shape of the gallbladder, its wall and lumen, as well as measurement of caliber and content of the common bile duct. Conventional portable ultrasound devices, ALOKA SSD-500 and SSD-1000 (B-mod) with convex 3.5 and 5 MHz probes were used. RESULTS: The cholecyst was normal in size (<120 x 50 mm) in 2164 (80.4%), and enlarged in 65 (2.4%) patients. The gallbladder was surgically removed in 163 (6.1%) patients, it was pseudoseptal in 141 (5.2%) and invisible in 44 (1.6%) patients. The gallbladder wall was normal in 2031 (75.5%), thickened in 259 (9.6%) and edematous in 173 (6.4%). Gallbladder calculosis was present in 310 (11.5%), and choledocholithiasis in 13 (0.5%) patients. CONCLUSION: Development of morphological abnormalities of the gallbladder and common bile duct was frequent in non-selected patients with infectious diseases. The majority of them may be detected by portable ultrasound devices, which makes them rather applicable for large clinical-epidemiological studies. PMID- 17853720 TI - [Physical activity as a direct cause of death]. PMID- 17853721 TI - Hyperopia in preschool and school children. AB - Hypermetropia (hyperopia) is a refractive error of the eye in which parallel light rays focus behind the macula luthea without accommodation giving an unclear retinal image. The involvement of accommodation in correction of far-sightedness lead to the following three clinical types of hvperopia: total, latent and manifest. Minor hyperopias can be successfully corrected by accommodation higher than +3.0D. If not corrected timely, they may cause amblyopia and esotropia, while high hyperopic anisometropia of a hyperopic eye, usually results in an amblyopic eye. The study included 200 children (400 eyes) within the age range of 3 to 18 years, and it was done following the assigned protocol in the course of clinical ophthalmologic check-ups. The most frequent refractive error in the examined children was hyperopia with hyperopic astigmatism, while anisometropia was found in 22% of children but the frequency was reduced in older children. Refractive family history was found in 60.50% of children. Hyperopia can result in poor visual development, occurrence of amblyopia and strabismus and therefore it represents a significant public health problem. As one of the most frequent amblyogenic factors in children, it can be eliminated/prevented by a screening program and adequate treatment providing prevention of amblyopia, which is a form of blindness. PMID- 17853722 TI - [The use of erythropoietin beta, two to three times per week, once per week and once every other week: meta-analysis of two clinical trials]. AB - INTRODUCTION: Renal anemia is a very common finding in patients with chronic kidney disease (CKD), both in patients not yet requiring dialysis and in patients on hemodialysis. Erythropoietin therapy is a gold standard in the treatment of renal anemia for more than 15 years. The aim of this meta-analysis was to assess the efficacy of different regimes of Recormon (erythropoietin beta, F. Hoffmann La Roche) in maintaining stable levels of hemoglobin (Hb) and hematocrit (HCT) in patients receiving hemodialysis. MATERIAL AND METHODS: Two multicenter open comparative three arm trials lasting for 24 weeks were conducted in Serbia and Montenegro, between 2004-2006, with a total of 216 patients from 23 hemodialysis centers (22 from Serbia and 1 from Montenegro). The inclusion criteria were as follows: stable Hb level (>100 g/l), ferritin level > 200 microg/l and transferrin saturation >20%. The patients also had to be on stable doses of Recormon, before starting the trial. A total of 203 patients finished the study according to the protocol, and their results were used for this meta-analysis. During the first 8 weeks all patients received the usual 2-3 times weekly dose of epo. 8 weeks later, 147 patients started receiveing epo once weekly, while 56 patients (group 1) continued on the 2-3 times dose during the entire study period. After another 8 weeks, 20 of those 147 patients receiving epo once weekly were transferred to once every week dose of epo (group 3), while 127 patients were on once weekly dose until the end of the trial (group 2). Primary efficacy parameter was the percentage of patients who maintained their target Hb and HCT level (>100 g/l and >30% for HB and HCT respectively). RESULTS AND DISCUSSION: The efficacy analysis included the per-protocol population (203 patients). Hb levels remained stable (>100 g/l) in all three groups. There were no statistically signifant differences in Hb levels between the groups, with mean Hb level > 11 g/dL in all three groups throughout the study. HCT levels also remained stable (>30%) in all three groups throughout the study, without statistical significance between visits and between groups. The average epo doses were not statistically different between groups, although group 3 had-slightly higher mean Hb level than groups 1 and 2. The main tolerability parameters. sitting systolic (SSBP) and diastolic (SDBP) blood pressures were monitored at all visits. Statistical analysis showed no difference in SSBP or SDBP between the visits or groups of patients throughtout the study, although one patient had to be excluded due to uncontrolled hypertension. Only one patient (0.5%) received one blood transfusion during both studies. CONCLUSION: All three dose regimens of subcutaneous epo beta were statistically equivalent in maintaining the target Hb and HCT levels. The use of epo once weekly or once every other week was not associated with dose increase, proving that optimization of treatment for every patient is possible in everyday clinical practice. The possibility of using 3 different dose regimes of epo beta, without compromising efficacy or increasing costs of treatment may be beneficial in the quest for better patient compliance. PMID- 17853723 TI - [C-fos protein expression in the parietal cortex and olfactory tubercle in the hypoxic rat brain]. AB - INTRODUCTION: We have attempted to identify which parts of the brain react to ischemic attack using the four-vessel occlusion model in rats. MATERIAL AND METHODS: We have monitored the expression of c-fos protein in the parietal cortex (R3 and T3) and in the olfactory tubercle (R4 and T4), regions which are supplied with blood by different arteries. The four-vessel occlusion was performed using the Pulsinelli's method and rats were divided into two groups: total ischemia (ligation of four blood vessels or coagulation of the vertebral artheries with bilateral ligation of carotid arteries - R group) and transient ischemic attack (ligation of four blood vessels or coagulation of the vertebral arteries with bilateral repeated ligation of carotid arteries - T group of rats, the so-called preconditioned group). Each of these groups had a control group. RESULTS AND CONCLUSION: The results showed pronounced expression of c-fos neurons in T group of rats which can explain longer survival of neurons. We believe that this model can serve as a good starting point to developing new approaches to the therapy of brain ischemia. PMID- 17853724 TI - [Electromyographic activity of the temporal and masseter muscles at different occlusal positions]. AB - INTRODUCTION: Normal occlusion or eugnathia, is a morphologically and functionally balanced bite. Differences in the form and function of orofacial structures cause morphological and functional deviations of the orofacial system. Irregular occlusal postitions may consequently change the electromyographic activity of the muscles of orofacial region. The aim of the research was an analysis and a comparative analysis of the bioelectrical activity of masticatory muscles in normal occlusion and distocclusion, in rest position, in the position of the central occlusion of the mandible and at the maximum voluntary muscle contraction. MATERIAL AND METHODS: The metodology of the research is based on electromyographic recording of the action potentials of the examined muscles in different mandibular positions. Registration of action potentials of the masticatory muscles was done using, facial, intramuscular, and coaxial electrodes, (Greenfield scheme) and measurements were performed on both sides. The research was carried out on a sample of 60 patients with an average age of 14,25 years. 30 subjects had normal occlusion and 30 had distal occlusion. RESULTS: The results were expressed in microvolts, as average cumulative amplitude voltages of action potentials, by means of which changes in the masticatory muscles were established and the degree of correlation between the electromyographic activity of the masticatory muscles and the occlusal type was analyzed. CONCLUSION: The results of the research show that the bioelectrical activity of the examined masticatory muscles falls in the group of subjects with distal occlusion, which is the result of a decreased number of active muscular tissues, or a decreased number of impulses coming into the muscle, or the combination of both. PMID- 17853725 TI - [Altered state of consciousness as a factor affecting the course and consequences of acute viral encephalitis]. AB - INTRODUCTION: Acute viral encephalitis is an infectious disease, which is characterized by sudden onset, serious clinical picture and with an uncertain outcome. Disturbances of consciousness are common in the course of acute viral encephalitis. Consciousness is the heighest form of psychic life and consciousness disturbances may include quantitative (somnolentia, sopor, coma) and qualitative symptoms (convulsions, twilight state). MATERIAL AND METHODS: We investigated 63 patients with acute viral encephalitis. The youngest patient was 15, and the oldest one 69 years of age. We examined the state of consciousness in all patients. RESULTS: Of all examined patients, 54 (85.72%) patients had disturbances of consciousness, 9 (14.25%) patients had no conciousness disturbances, 11 (17.46%) patients had sopor and 24 (38.09%) patients were in coma. The highest percentage of lethal outcomes was recorded in coma patients (12.5%). The longer the duration of consciousness disturbances, the higher the mortality among these patients. DISCUSSION: Subjective and objective factors cause different grades and duration of consciousness disturbances. The highest percentage of patients who recovered without consequences was established in the group of patients (81.82%) with somnolence. The highest percentage of patients who recovered with consequences (20.8%) and patients (12.5%) with lethal outcome was recorded in the group of patients in coma. These findings are in correlation with literature data. PMID- 17853726 TI - [Treatment of low HDL-cholesterol levels in the reduction of cardiovascular risk]. AB - INTRODUCTION: Although reduction of LDL-C levels is a priority in the treatment of dyslipidemia, not all coronary events are prevented despite aggressive LDL-C lowering, and risk reduction can be improved by treating additional lipid abnormalities. The Framingham Study was the first to demonstrate the inverse relationship between HDL-C and risk of coronary heart disease (CHD). This relationship was present at all levels of LDL-C, whereas the highest risk was associated with low HDL-C and high LDL-C. THE ANTIATHEROGENIC ACTIONS OF HDL CHOLESTEROL: The antiatherogenic actions of HDL-C are complex. HDL-C plays a major role in reverse cholesterol transport, mobilizing cholesterol from the periphery to the liver. In addition, cardioprotective effects of HDL-C include endothelial protection, anti-inflammatory activity, as well as antioxidant and antithrombotic effects. TREATMENT OF LOW HDL CHOLESTEROL: In addition to lowering LDL-C, statins increase HDL-C by 5 to 15% by increasing apolipoprotein A-I synthesis. Fibrate therapy results in an increase in HDL-C of 10 to 25 % by activating PPAR- , which stimulates hepatic apolipoprotein A-I gene expression. Niacin is the most effective agent used for increasing HDL-C, causing increase of 15 to 35%. The side effects of niacin therapy, which is largely mediated by prostaglandins, may be minimized by the use of prolonged-release formulation of nicotinic acid. Combination therapy with HDL-raising agents, such as nicotinic acid and statin, markedly increases HDL-C, lowers LDL-C and improves the lipoproteins subclass distribution. CONCLUSION: New therapeutic modalities in the treatment of low HDL-C and lowering LDL-C, either in combination or as a monotherapy, may provide additional benefits in reducing CHD risk. PMID- 17853727 TI - [Etiological aspects of anterior open bite]. AB - INTRODUCTION: Open bite is a multifactorial phenomenon and no single factor can account for open-bite. Etiology plays an important role in diagnosis. Heredity, unfavorable growth patterns, incorrect jaw postoure, are the characteristics of skeletal open bite. DIGIT SUCKING: Depending on where the thumb is placed, a number of different types of dental problems can develop. Malocclusions of the late mixed or permanent dentitions, caused by thumb sucking are not self corrected and orthodontic treatment is necessary for their correction. LYMPHATIC TISSUE: In order to produce oral respiration, the mandible is postured inferiorly with the tongue protruded and resting against the oral floor. This postural alteration induces dental and skeletal modifications similar to those caused by thumb sucking. This may cause excessive eruption of the posterior teeth, leading to an increase in the vertical dimension of the face and result in development of anterior open bite. TONGUE THRUST: Tongue habits cause an anterior open bite or they develop secondarily to thumb sucking. In skeletal open bite the tongue habit acts as a secondary factor which helps to maintain or exacerbate the condition. Many orthodontists have had a discouraging experience of completing dental treatment, with what appeared to be good results, only to discover that the case had relapsed because the patient had a tongue thrust swallowing pattern. CONCLUSION: Dentoalveolar or habitual open bite is caused by habits, which influence the growth and development of dentoalveolar processes and contribute to occlusal disharmonies. Prior to eruption of adult dentition, open bite related to oral habits is usually not a concern as when the habits stop, because the erupting dentition tends to improve spontaneously. Treatment is usually not necessary until permanent teeth erupt (approximately 6 years old). PMID- 17853729 TI - Duplex Doppler sonography in portal hypertension. AB - Conventional echotomography and duplex Doppler ultrasonography are noninvasive imaging techniques in measurement of hepatic blood flow. In the period from February 2002 to March 2004, 29,086 patients underwent ultrasound examination at the Institute of Radiology in Novi Sad, and 17,503 presented with symptoms of gastroenterology diseases and/or hepatobiliary tract diseases. 984 patients underwent duplex Doppler sonography. This prospective study included 50 patients with suspected or confirmed diagnosis of portal hypertension. All patients were examined using Siemens Versa Pro (3.5 MHz convex probe: B-mode, color and pulse Doppler). The following parameters were evaluated: Doppler sonoscore, congestion index and portal vein thrombosis. By analyzing gathered data, the diagnosis of portal hypertension was confirmed in 10% of patients at baseline, and in 6% of patients at last follow-up, six months later. Results of this investigation demonstrate the importance of duplex Doppler ultrasonography as an excellent noninvasive diagnostic method used for visualization of the direction and velocity of blood flow, as well as presence of portal vein thrombosis. This imaging modality is used as an initial diagnostic tool in the evaluation of the portohepatic circulation, especially in portal hypertension syndrome and in suspected portal vein thrombosis. PMID- 17853728 TI - [Electrophysiological characteristics of the athlete's heart]. AB - INTRODUCTION: The athletic heart syndrome is characterized by morphological, functional and electrophysiological alterations as an adaptive response to vigorous physical activity. Athletes heart is predominantly associated with a programmed, intensive training. But as there are different kinds of physical activities, the degree of these changes is highly variable. ELECTROPHYSIOLOGICAL CHARACTERISTICS OF THE ATHLETE'S HEART: The response of the body to vigorous physical activity is a multiorgan system phenomenon. The integrated functioning of each of these organ systems is very important, but the cardiovascular system plays a critical role in mediating the activity. Because of that, most changes in the neurohumoral regulation predominantly affect the cardiovascular system. These changes include: depression of sympathetic activity and stimulation of parasympathetic activity, so electrophysiological characteristics of the athlete's heart must differ from the sedentary Although these facts, are well known, the athlete's heart is not a precisely defined concept. It is a gray zone between physiology, and pathology. CONCLUSION: Considering the number of sudden cardiac deaths in athletes, it is needless to say how important it is to distinguish physiological changes of the heart due to physical activity, and pathological changes due to some cardiac diseases. PMID- 17853730 TI - [The primary health care and its role in the reproduction of the population of Vojvodina]. AB - INTRODUCTION: The problem of depopulation has been a serious threat to the province of Vojvodina leading to changes in the age structure, decrease in working and defensing population, increase in health and social service costs. The aim of this study was to examine how to improve women's health care at primary level during prenatal, perinatal and postnatal period in order to give birth to a healthy child, preserve general and genital health and promote the ability to take care of the child and give birth to another child or children. MATERIAL AND METHODS: The investigation included 300 patients (100 patients from each center: health centers in Temerin, Mali Idos and Zitiste) of reproductive age. All patients completed an anonymous questionnaire with 24 questions by choosing one of the offered answers or by writing an answer where necessary - concerning the primary health care and its role in the reproduction of the population of Vojvodina. RESULTS: Half of the investigated patients did not use contraception. 32.66% of women visited their GP to control their pregnancies: 26.33% to treat their diseases, 11.33% for contraception advice, 2.66% for treatment of infertility and 27.33% for other reasons. More than half of the polled patients thought that there was a need for improvement of the work in women's health centers. 74.66% of patients suggested education on different types of health care and family planning associated with the use of modern equipment for diagnostics (13.33%). CONCLUSION: The primary health care has a significant role in the process of reproduction of the population and these results point to the necessity of a more active role in the improvement of women's health, as well as in the implementation of measures in the population planning policy. PMID- 17853731 TI - [The effects of air pollution on the frequency of respiratory symptoms in the population of Nis and Niska Banja]. AB - INTRODUCTION: Ambient air pollution, particularly in densely populated urban areas, is a major risk factor for the health of the exposed population. The respiratory tract is the primary target for air pollutants. The aim of this study was to evaluate the effects of' long-term exposure to air pollution and incidence of respiratory symptoms and diseases. MATERIAL AND METHODS: Measurements of air pollutants: sulphur dioxide and soot particles, were carried out daily at the Institute of Public Health in Nis at two locations, in Nis and in Niska Banja, during the period 1999-2003. The Air Quality Index was calculated for both areas. The investigation included 654 women, nonsmokers, between 20-30 years of age, from two areas with different levels of common air pollutants. The prevalence of respiratory symptoms and diseases was determined on the basis of a modified WHO standard questionnaire completed by doctors. RESULTS: The obtained results show that examinees from Nis had a statistically higher prevalence of some respiratory symptoms (cough with cold and phlegm) whereas women from Niska Banja had a statistically significantly higher prevalence of lower respiratory tract diseases. CONCLUSION: Long-term exposure to low concentrations of air pollutants is a contributing factor to the development of respiratory symptoms and diseases. PMID- 17853732 TI - [Implications of HLA linkage disequilibrium phenomenon in finding unrelated volunteer bone marrow donors]. AB - INTRODUCTION: The distribution of HLA genes and haplotypes in the normal population is of considerable importance in disease susceptability studies, population and genetic studies and tissue and organ transplantation. The HLA phenotype frequencies can be used for the estimation of the probability of finding phenotypically identical unrelated volunteer bone marrow donors. It has been presumed that patients with HLA haplotypes in strong linkage disequilibrium, a have higher probability of finding HLA identical unrelated donors than others. MATERIAL AND METHODS: HLA gene and haplotype frequencies were calculated, as well as delta values and their significance. The implications of HLA disequilibrium phenomenon in unrelated donor search, was investigated by calculating the correlation coefficient between frequencies of haplotypes showing significant delta values and the linkage disequilibrium coefficient, as well as between the average number of donors necessary for research. RESULTS: Haplotypes showing the highest delta values are at the same time the most frequent haplotypes (A1B8:0,1188 and 0,145; A3B35:0,0722 and 0,1;A2B12:0,055 and 0,105). In patients who have both haplotypes showing significant delta values (e.g. A2B5/A3B35), the number of donors necessary for research is clearly lower than in patients who have only one given haplotype, or have no such haplotypes. CONCLUSION: Our results showed that patients with HLA haplotypes showing significant delta values have a higher probability of finding HLA identical unrelated donors. PMID- 17853733 TI - [Vascular access blood flow for hemodialysis--a risk factor for development of cardiovascular complications in hemodialysis patients]. AB - INTRODUCTION: Vascular access blood flow rate of 100-350 cm/s and between 500 and 1000 ml/min, points to normal vascular access function and adequate hemodialysis. High blood flow through the arteriovenus fistula overloads the left ventricle inducing left ventricular remodiling. MATERIAL AND METHODS: The aim of the study was to establish the degree of correlation between blood flow through the vascular access for hemodialysis and echocardiographic parameters for the assessment of left ventricular hypertrophy and left ventricular dilatation and left ventricular function. The research included 115 patients (M:F 71:44), average age 53.30+/-12.17 years, average length of dialysis 4.51 +/- 4.01 years and average Kt/Vsp index 1.17+/-0.23. RESULTS: The average blood flow through the vascular access for hemodialysis was 662.27+/-301.59 ml/min. EDDLV 54.52+/-6.42 mm, and EDVi 100.80+/-34.62 ml/m2. There is a statistically significant positive correlation between blood flow through vascular access for hemodialysis and EDDLV and EDVi. CONCLUSION: High blood flow through the vascular access for hemodialysis is an independent risk factor for the development of cardiovascular complications in patients on hemodialysis. PMID- 17853734 TI - [Surgical treatment of a giant extracranial internal carotid artery aneurysm--a case report]. AB - INTRODUCTION: True aneurysms of the extracranial internal carotid artery are rare lesions. Surgical treatment is considered to be the best therapeutic option. However, the use of the intraluminal shunt remains controversial. CASE REPORT: We reported a case of a giant extracranial internal carotid artery aneurysm treated by reconstructive surgery. A 76-year-old woman was referred with a pulsatile mass inside her mouth, associated with dizziness and dysarthria. There was no history of cerebrovascular symptoms, neck pain, or cervical trauma. A magnetic resonance scan showed a 45 mm aneurysm of the internal carotid artery (ICA), and kinking of ICA. Angiography demonstrated a saccular ICA aneurysm, with a lengthening and tortuosity of the ICA. The aneurysm and the carotid artery branches were easily exposed through a standard anterior cervical incision. After resection of the aneurysm, a Javid shunt was inserted between the common and internal carotid arteries, and end-to-end repair of ICA was easily performed due to ICA redundancy. The aneurysm was of atherosclerotic origin. Four months after the operation, the patient showed a complete recovery from peripheral neurological deficit. DISCUSSION: Our results show that surgical reconstruction is a satisfactory therapeutic choice in the management of extracranial carotid artery aneurysms in order to avoid rupture, thromboembolism and cerebrovascular insufficiency. To date, there has been little experience with endoluminal exclusion techniques and the long-term effectiveness is still uncertain. PMID- 17853735 TI - [Congenital hairy polyp of the nasopharynx--a case report]. AB - INTRODUCTION: Hairy polyps are very rare benign tumors that can occur anywhere in the body, and they are the most common congenital nasopharyngeal masses. CASE REPORT: A two-day-old full-term female was admitted to the newborn Special Care Unit with noisy breathing, intermittent upper airway obstruction and feeding difficulty. A 3.4 kg infant was born by spontaneous vaginal delivery to a healthy mother, following a normal pregnancy. On admission, she presented with noisy inspiratory breathing which was louder and more labored in prone position. Flexible endoscopy showed a pale sausage-like mass protruding from nasopharynx just behind the soft palate, to the oropharynx and back. A computed tomography scan showed a 1.8 cm round mass in the right nasopharynx, with central fat density and no intracranial communication. The mass was excised transorally with no evidence of a residual tumor. The infant made a full and uneventful postoperative recovery. DISCUSSION: Hairy polyps usually occur as isolated defects and they are not associated with other congenital anomalies. Genetic predisposition has not been established. It does not have malignant alteration. However, there is some confusion about the histological classification of these lesions. One theory supports the idea that hairy polyps originate from disturbed development of stomodeum in the 28th week of gestation and regression of the nasopharyngeal membrane. The second theory supports the idea of origin from the first or second bronchial arch. Probably the best assumption would be that it develops as a special and unique entity. CONCLUSION: Hairy polyp is an unusual malformation that most frequently appears during the first days after birth. Complete resection provides permanent cure. PMID- 17853736 TI - [Diseases caused by bacteria and rickettsia in biological warfare and bioterrorism]. AB - INTRODUCTION: Until recently, the use of biological weapons was considered more from an academic than practical point of view. The list of agents and/or toxins that can be used as biological weapons is long. Some of them are highly lethal, while others cause morbidity and disability. BIOLOGICAL WEAPONS: Bacteria, rickettsia, viruses, fungi, protozoa and toxins can all be used as biological weapons. The infection may be acquired by inhalation of aerosols, ingestion of contaminated water or food or direct contact with infectious agents. Early recognition, diagnosis and treatment of these patients is of utmost importance. Special attention must be given to the use of genetically modified microorganisms. Medical protection from biological weapons is very important as well as continuous education. CONCLUSION: This article describes the main clinical characteristics of anthrax, cholera, plague, Q fever, tularemia, brucellosis, and glanders, as biological weapons, their diagnostics, treatment and basic prevention measures. PMID- 17853737 TI - [Jewish physicians in Senta from 1822 to 1944]. AB - In the introduction, the authors focused on the settlement of Jews in Senta and analyzed the Jewish humanitarian associations and organizations working in the period from 1850 to 1944. The study included the period from 1771 to 1944. The Historical Archive of Senta provided personal and professional data of Jewish physicians working in Senta during this period. In some cases, certain data are missing, but the authors decided to include these physicians as well, considering the possibility of furthering the investigation. In the period from 1822 - 1944, the following Jewish physicians were working in Senta: Dr. Samuel Boros, Dr. Jozua Veksler, Dr. Simon Slezinger, Dr. Zigmond Veksler, Dr. Jozef Kelner, Dr. Adolf Glikstal, Dr. Mor Lendvai, Dr. Sandor Bergel (Meri), Dr. Jozef Reicer, Dr. Lipot Kovac, Dr. Andor Glikstal, Dr. Kornel Gereg (Goldstajn), Dr. Lajos Vajda, Dr. Sandor Fles, Dr. Andor Senes, Dr. Mihalj Dajc, Dr. Josif Singer, Dr. Erne Stesel, Dr. Boriska Garai (Malenkovic), Dr. Istvan Frank, Dr. Andras Majer, Dr. Geza Glikstal, Dr. Jakob Svarc, Dr. Kalman Vig, Dr. Jene Vajs, Dr. Imre Miler, Dr. Istvan Gere, Dr. Andras Samuel, Dr. Josip Stajner, Dr. Sandor Singer and Dr. Derd Polacek. Apart from biographies, this paper also contains photos of some physicians. PMID- 17853738 TI - Paying dues by doing less. AB - The ACHE's streamlining of its credentialing process has some complaining the move waters down the designation's prestige. The two-tier certification was replaced with a one-step process that led to a nearly 19-fold increase in the number of fellows named this year. "The gold standard was always the FACHE," says Christopher Cornue, left. PMID- 17853739 TI - Windber leaves Conemaugh. Pa. facility's decision a sign of hospital-system relations. PMID- 17853740 TI - San Francisco's solution. Plan to cover uninsured already facing lawsuit. PMID- 17853741 TI - Texas Health looks to grow. System intends to acquire, build in north Texas. PMID- 17853742 TI - Fear of change itself. A few positive developments only underscore healthcare's hidebound nature. PMID- 17853743 TI - Homegrown leaders. How one health system made mentoring an integral part of its operations. PMID- 17853744 TI - Seeking synchronization. AHRMM meeting focuses on global supply tracking. PMID- 17853745 TI - Caught in the middle. Racketeering lawsuit centers on role of hospitalists. PMID- 17853746 TI - By the numbers. Largest master's programs in health administration. Ranked by total number of students enrolled, based on 2006-07 survey of programs i. PMID- 17853747 TI - Big guys getting bigger: study. Small doc practices still lead, but numbers shrinking. PMID- 17853748 TI - [Multiple central clinical test of electroacupuncture at Jiaji (EX-B 2) combined with laser needle-knife for treatment of lumbar disc herniation]. AB - OBJECTIVE: To observe therapeutic effect of electroacupuncture (EA) at Jiaji (EX B 2) combined with laser needle-knife on lumbar disc herniation. METHODS: One hundred and twenty cases of lumbar disc herniation were divided into an Jiaji EA group, a laser needle-knife group and a combination group (Jiaji EA plus laser needle-knife) according to random number table. Changes of symptoms at different stages before and after treatment were investigated with SF-MPQ cumulative scores. RESULTS: All the 115 cases completed all of the study, SF-MPQ score in the combination group was significantly lower than those in the Jiaji EA group and the laser needle-knife group (P<0. 01, P<0.05), with a significant difference at the end of treatment of 2 weeks (P<0.01) between the laser needle-knife group and the Jiaji EA group, and with no significant difference at treatment of 1 week and 3 weeks (P>0.05). The recurrence rate at a half year later in the combination group was significantly lower than those in laser needle-knife group and the Jiaji EA group (P<0.05). CONCLUSION: EA at Jiaji (EX-B 2) combined with laser needle-knife can significantly increase clinical therapeutic effect, alleviate pain of the patient and reduce recurrence. PMID- 17853749 TI - [Study on the therapeutic effect of electroacupuncture on migraine and influencing factors]. AB - OBJECTIVE: To compare therapeutic effects of electrical acupuncture (EA) at Qiuxu (GB 40) and Tianshu (ST 25), and to probe the factors of influencing the therapeutic effect. METHODS: Two hundred and seventy-five cases were randomly divided into the test group of 138 cases treated with EA at Qiuxu (GB 40) and the control group of 137 cases treated with EA at Tianshu (ST 25). Their therapeutic effects were observed and the factors influencing the therapeutic effect were analyzed. RESULTS: The transient effective rate was 70.3% in the test group and 58.4% in the control group with a significant difference between the two groups (P<0.05), and there were very significant differences between the two groups in the therapeutic effects at treatment of 4 weeks, and following-up 3 and 6 months later (P<0.001), the transient analgesic effect of EA at Qiuxu (GB 40) being better. EA had better transient effect on migraine for the mental workers, or the patient with high pain score at treatment, or more frequent attack. The long-term analgesic effect of EA at Qiuxu (GB 40) was better than Tianshu (ST 25). CONCLUSION: The analgesic effect of EA at Qiuxu (GB 40) is better than Tianshu (ST 25) and the profession and conditions of the patient are the factors influencing the therapeutic effect. PMID- 17853750 TI - [Clinical observation on abdominal acupuncture plus Madopa for treatment of Parkinson's disease]. AB - OBJECTIVE: To find out an effective therapy for Parkinson's disease. METHODS: Sixty cases were randomly divided into an abdominal acupuncture group and a control group, 30 cases in each group. The abdominal acupuncture group were treated with Madopa and abdominal acupuncture at Zhongwan (CV 12), Xiawan (CV 10), Qi-hai (CV 6) and Guanyuan (CV 4), etc. ; and the control group were treated with Madopa. RESULTS: After treatment of 3 courses, the effective rate was 90.0% in the abdominal acupuncture group and 83.3% in the control group with a significant difference between the two groups (P<0.05). CONCLUSION: Abdominal acupuncture combined with Madopa can elevate therapeutic effect of Madopa and reduce adverse effects of Madopa for the patient of primary Parkinson's disease. PMID- 17853751 TI - [Effect of acupuncture-moxibustion combined with nerve growth factor on compensation of cerebral function in the children of cerebral palsy]. AB - OBJECTIVE: To investigate the compensation of cerebral function in acupuncture for rehabilitation of cerebral palsy. METHODS: One hundred children of cerebral palsy were randomly divided into a treatment group and a control group, 50 cases in each group. The treatment group were treated with scalp acupuncture at the Motor Area, Foot Motor Sensory Area and Equilibrium Area, body acupuncture at Binao (LI 14), Fengchi (GB 20), Huantiao (GB 30), etc. and injection of nerve growth factor into Zusanli (ST 36), in combination with rehabilitation training; the control group were treated only with rehabilitation training. Their clinical therapeutic effects and recoveries of brain lesion detected by CT, SEPCT were investigated. RESULTS: The total effective rate was 84.0% in the treatment group better than 52.0% of the control group. After treatment, the development quotient (DQ) in the treatment group was higher than the control group (P<0.01). CONCLUSION: Acupuncture can promote compensation of cerebral function in the children of cerebral palsy. PMID- 17853752 TI - [Observation on the therapeutic effect of ear point combined therapy on common migraine at the remission stage and effects on plasma CGRP and ET in the patient]. AB - OBJECTIVE: To probe into the therapeutic effect of ear point combined therapy on common migraine at the remission stage and the mechanism. METHODS: Thirty-two cases of common migraine at the remission stage were treated with ear point combined therapy, including blood-letting at ear back, injection of autoblood into Fengchi (GB 20), Yanglingquan (GB 34), and pricking at ear points Nie, Yi dan (pancreas and gallbladder), Shenmen, etc.. Clinical therapeutic effect was evaluated at the end of one therapeutic course, and calcitonin gene-related peptide (CGRP) and endotheline (ET) were detected before and after treatment, and the CGRP and ET contents were compared with those in 22 normal persons. RESULTS: The effective rate was 78.1% (P<0.001), CGRP and ET contents had very significant changes after treatment (P<0.01), and CGRP and ET showed negative correlativity (P<0.05). CONCLUSION: The ear point combined therapy can regulates the balance between the plasma CGRP and ET in the patient of common migraine and improve vasodilative, vasoconstrictive and endothelial fuctions in the brain, hence stopping pain. PMID- 17853753 TI - [Clinical observation on acupuncture at the five-zangshu for treatment of perimenopausal syndrome]. AB - OBJECTIVE: To observe therapeutic effect and safety of acupuncture at the five zangshu for treatment of perimenopausal syndrome (PMS). METHODS: Forty cases of PMS were randomly divided into a treatment group and a control group, 20 cases in each group. The treatment group were treated with acupuncture at the five-zangshu and the control group with oral administration of Premarin tablets. The therapeutic effects and changes of Kupperman scores, and serum estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH) levels before and after treatment were observed. RESULTS: The total effective rate was 90. 0% in the treatment group which was better than 65.0% in the control group (P<0. 05). After treatment, serum E2 level significantly increased (P<0.01), with a significant difference between the two groups (P<0.05), and with a significant difference between the two groups in Kupperman symptom score index (MI) after treatment (P<0.05). CONCLUSION: Therapeutic effect of acupuncture at the five zangshu is better than that of Premarin for treatment of perimenopausal syndrome. PMID- 17853754 TI - [Medicine-separated moxibustion combined with healthy guidance for improving human sub-healthy state]. AB - OBJECTIVE: To observe results of medicine-separated moxibustion combined with healthy guidance for improving human sub-healthy state and to probe the mechanism. METHODS: Fifty-two sub-healthy persons from community were selected with health valuation method of traditional Chinese medicine and were treated with healthy guidance and medicine-separated moxibustion at selected points according to causes of disease, syndrome, clinical manifestations. At the same time, changes of clinical physical and chemical indexes and clinical symptoms before and after treatment were monitored. RESULTS: After treatment, clinical symptoms and natural killer cells (NK) activity significantly increased (P<0.05); complement C3 and C4 levels significantly decreased and IgG level significantly increased (both P<0.05). CONCLUSION: Medicine-separated moxibustion combined with healthy guidance direction can regulate functions of zang- and fu-organs and elevate immunity in the people of sub-healthy state, so as to improve sub-healthy state and increase quality of life. PMID- 17853755 TI - [Clinical observation on acupuncture for treatment of allergic rhinitis]. AB - OBJECTIVE: To find out an effective acupuncture and moxibustion therapy for allergic rhinitis. METHODS: One hundred and thirty-five cases were randomly divided into a treatment group, a control group I , and a control group II , 45 cases in each group. The treatment group were treated with acupuncture at Yingxiang (LI 20), Shangyingxiang (EX-HN 8), Yintang (EX-HN 3), Hegu (LI 4), Fengchi (GB 20), Dazhui (GV 14), Feishu (BL 13); the control group I with Yingxiang (LI 20), Shangyingxiang (EX-HN 8), Yintang (EX-HN 3), Hegu (LI 4), and the control group II with oral administration of Biyankang tablets, 4 tablets each time, thrice each day. Acupuncture was given one session daily, 10 sessions constituting one course. Their therapeutic effects were compared after treatment of 2 courses and were followed up a half year later. RESULTS: The total effective rate was 91.1% in the treatment group, 71.1% in the control group I and 46.7% in the control group II, with a significant difference among the 3 groups (P<0.05), and with a significant difference in the recurrence rate one year later among the cured cases of the 3 groups (P<0.05). CONCLUSION: Acupuncture has a definite therapeutic effect on allergic rhinitis, with a better result by acupuncture with the anterior and posterior acupoint association method. PMID- 17853756 TI - [Explanation of essence and substance basis of channels and collaterals with fasciology]. AB - In our research of digital human body, construct of image structures close to the recorder of human channels and collaterals, and trace back to development biology of connective tissue and process of organic evolution, and it is concluded that connective tissue bracket in human body may constitute a new functional system- human self-supervision and control system, meanwhile, we propose a new study field, fasciology. The significance is that it introduces a new functional system in human body and develops new field of scientific research; and it annotate biological foundation and therapeutic mechanisms of traditional Chinese medicine therapy, which provides medical biological foundation for modern channel research of traditional Chinese medicine; it proposes a suggestion for development strategy of traditional Chinese medicine. PMID- 17853757 TI - [Study on the morphological evidence of five-shu-point]. AB - OBJECTIVE: To search for the morphological evidence of five-shu-point so as to explain the theory of the five-shu-point more reasonably. METHODS: Carefully study on Yellow Emperor's Internal Classic and compare with the modern anatomic knowledge. CONCLUSION: The theory of five-shu-point is closely related with the theory of blood vessels. The distributional pattern of the superficial vein on the remote parts of the limbs (below the elbow or the knee joints) is the morphological basis for the theory of five-shu-point. PMID- 17853758 TI - [Power view of transmission of channels and collaterals]. AB - OBJECTIVE: To describe physiology of channels and circulation of qi and blood from the point of view of mechanics. METHODS: The equation of no compressive normal Newtonian fluid electric osmotic motion are solved by using numerical value method. RESULTS: The results of numerical value calculation show that the flow rate of fluid of channel lines is confirm to the migration velocity of middle-small molecules in literature. When the osmotic coefficient of blood vessel wall and blood pressure of the end of artery changes, the flow rate of qi will correspondingly change, which is confirm with the physiologic reaction at acupuncture. If the static pressure of the channel lines and the inflow condition are changed, it can explain the theory of qi stagnation and blood stasis, and flow of qi inducing blood circulation. CONCLUSION: By using the equation of electric osmotic flow, the theory of traditional Chinese medicine can be explained, which is conducive to understanding the conduction phenomena of electric wave and electric current of channels and collaterals. PMID- 17853759 TI - [Effects of acupuncture at "Sifeng" (EX-UE 10) on serum zinc and gastric emptying rate in the rat of experimental spleen deficiency]. AB - OBJECTIVE: To probe the mechanism of acupuncture at Sifeng (EX-UE 10) for treatment of infant anorexia. METHODS: Healthy rats were randomly divided into a control group, a model group and an acupuncture group. The model rats were made by intramuscular injection of Reserpine. The acupuncture group were treated with pricking at Sifeng (EX-UE 10) once daily for 2 weeks. After that, the gastric emptying rate and contents of Zn in the red cell and serum were observed in all the groups. RESULTS: Compared with the model group, the gastric emptying rate was accelarated, and the serum Zn content was increased in the acupuncture group (P<0.01, P<0.05). CONCLUSION: Acupuncture at Sifeng (EX-UE 10) has significant therapeutic effect on the rat with spleen deficiency, accelerating the gastric emptying rate and increasing the serum Zn content. PMID- 17853760 TI - [Effects of electroacupuncture of different frequencies on slimming effect in the rat of experimental obesity]. AB - OBJECTIVE: To compare the slimming effects of electroacupuncture of different frequencies. METHODS: The rats were randomly divided into a control group, a model group, an acupuncture group I (30 Hz), and an acupuncture group II (100 Hz). Acupoints selected were "Housanli" (ST 36), "Sanyinjiao" (SP 6), "Guanyuan" (CV 4), "Zhongwan" (CV 12). The changes of Lee's index, fat weight around the left kidney and the volume of the fat cell, blood lipids, insulin and leptin before and after treatment were compared. RESULTS: Compared with the model group, Lee's index, fat weight around the left kidney and the volume of the fat cell, blood lipids significantly changed in the two acupuncture groups (P<0.01), with the acupuncture group II being more change than that of the acupuncture group I (P<0.05); and compared with the model group, the leptin level decreased in the two acupuncture group (P<0.01) and the serum insulin level decreased (P<0.05) , with no significant difference between the acupuncture group I and the acupuncture group II (P>0.05). CONCLUSION: Electroacupuncture of different frequencies has different effects on fat metabolism in fat rats, and electroacupuncture of 100 Hz has a better effect than 30 Hz on obesity. PMID- 17853761 TI - [Systematic evaluation of the therapeutic effect and safety of Xingnao Kaiqiao needling method in treatment of stroke]. AB - OBJECTIVE: To evaluate the therapeutic effect and possible adverse effects of Xingnao Kaiqiao needling method in treatment of stroke. METHODS: Adopt Cochrane system assessment methods. RESULTS: Altogether 25 studies and 4 377 cases of stroke were enrolled. Xingnao Kaiqiao needling method had the tendency to decrease the fatality and the disablement rate, and it was better than the control group in improvement of nerve defect score and the therapeutic effect. In the studies enrolled, only 2 cases of pain were found. CONCLUSION: Xingnao Kaiqiao needling method is safety and effective for stroke. PMID- 17853762 TI - [Professor Tian Wei-zhu's clinical experiences in acupuncture treatment of stroke]. AB - Professor Tian Wei-zhu, a national famous physician and an acupuncture specialist. He has consummate skill of acupuncture and profound theories, and clinically, he is good at application of eye acupuncture with rich experiences. The present paper introduces professor TIAN's clinical experiences including combination of both yin channels with yang channels, and combination of eye acupuncture with body acupuncture in treatment of stroke; standardized acupuncture manipulation, and emphasizing acupuncture effects; stressing treatment by stages and paying attention to acupuncture regulation at the spasm stage for treatment of hemiplegia. PMID- 17853763 TI - [Brief analysis on scientifity of the international scalp acupuncture]. AB - By comparing and analyzing the similarity among the international scalp acupuncture, JIAO's scalp acupuncture and ZHU's scalp acupuncture, it is believed that the international scalp acupuncture is a combination of traditional acupuncture and other scalp acupuncture on the basis of channel theory of TCM, and this combination is worthy of discussion. However JIAO's scalp acupuncture lacks scientific evidence. So, the international scalp acupuncture following most contents of JIAO's scalp acupuncture is worthy of discussion. PMID- 17853764 TI - [Origination and development of "heat in middle-jiao", a disease symptom of the channel in unearthed literature of channels]. AB - Based on the Records of the Historian, Biographies of Bianque Canggong and analysis on relative early literature, it is known that "heat in the middle-jiao" can form "oliguria, dark urine" and other symptomes of urine, which was an early medical view and commonly accepted in that time. Affected by this view, the "urine retention due to heat in middle-jiao" appeared in early channel symptoms of the Foot-Jueyin Channel closely related with the urine symptoms. This early channel disease symptoms still was reflected in Plain Questions Zhenyao Jingzhong Lun, Plain Questions Maijie, and Miraculous Pivot Zhongshi. In Yellow Emperor's Internal Classic, "heat in middle-jiao" had became the concept with zang-fu meanings. In Miraculous Pivot Jingmai at being publish ed, because of the influence of obvious differentiation between channels and zang-fu theories, "heat in middle-jiao" was not enrolled in disease symptoms of channels. In the present study, it is indicated that formation of early disease symptoms of channels has quitely wide medical background, if the study of disease symptoms of channels is divorced from this background, it will produce error. PMID- 17853765 TI - [Advances of clinical studies on acupuncture and moxibustion for treatment of periodontitis]. AB - Periodontitis is a chronic inflammatory disease of multiple causes with easy relapse. It is difficult to be cured completely and permanently. The effectiveness of acupuncture and moxibustion therapy is rapid and reliably in treatment of pain and gingival swelling complicated by periodontitis. Combination of acupuncture and moxibustion with scaling, gargle had better effects in eliminating gingival inflammation, relieving periodontal packet and teeth mobility, which need to be confirmed by more clinical control researches with standard periodontal parameters and criteria of therapeutic effects. PMID- 17853766 TI - [Multiple central clinical studies on the needling method for regulating wei and strengthening brain for treatment of insomnia]. AB - OBJECTIVE: To observe the clinical therapeutic effect of the needling method for regulating wei and strengthening brain on insomnia. METHODS: Two hundred cases of insomnia were randomly divided into a test group and a control group, 100 cases in each group. The test group were treated with the needling method for regulating wei and strengthening brain with Baihui (GV 20), Dazhui (GV 14), Shenmai (BL 62), Zhaohai (KI 6) and ear points Yuanzhong, Shenmen selected; and in the control group, Sishencong (EX-HN 1), Shenmen (HT 7) and Sanyinjiao (SP 6) were selected. Acupuncture was given once daily for 15 days. Pittsburgh sleep quality index (PSQI) was used for scoring before and after treatment. RESULTS: The total effective rate was 89.0% in the test group and 65.0% in the control group with a very significant difference between the two groups (P<0.01); the difference of PSQI scores before and after was -9.15+/-5.68 in the test group and -5.64+/-5.73 in the control group, with a very significant difference before and after treatment in the two groups (P<0.01). CONCLUSION: The therapeutic effect of the needling method for regulating wei and strengthening brain on insomnia is better than that of normal needling method. PMID- 17853767 TI - [Observation on therapeutic effect of ear point blood-letting combined with cupping on Back-shu points for treatment of acne vulgaris]. AB - OBJECTIVE: To compare clinical therapeutic effects of combined ear point blood letting therapy, oral administration of medicine and external application of medicine on acne vulgaris. METHODS: The patients of acne vulgaris were randomly divided into a treatment group and a control group. The treatment group were treated with ear point blood-letting combined with cupping at Back-shu points; and the control group with oral administration of Tetracycline and external application of Cuochuangping Ointment. RESULTS: After treatment of 1approximately 3 courses, the cured rate (50.0%) and the total effective rate (92.9%) in the treatment group were significantly higher than 17.6% and 76.5% in the control group with a very significant difference between the two groups (P<0.01); a half year later, the recurrence rate or the deteriorative rate in the treatment group was significantly lower than that in the control group (P<0.01). CONCLUSION: The therapeutic effect of ear point blood-letting combined with cupping at Back-shu points is significantly better than that of oral administration of Tetracycline and external application of Cuochuangping Ointment. PMID- 17853768 TI - Effects of citalopram and fluoxetine on the corticocerebral blood flow in conscious rabbits. AB - Depression, which is associated with an increased incidence of vascular events, frequently occurs following stroke. Selective serotonin reuptake inhibitory drugs (SSRIs) as antidepressants, are well tolerated, and also seem to be effective in post-stroke depression. The aim of this study was to investigate the effects of the SSRIs citalopram and fluoxetine, on the corticocerebral blood flow (cCBF) in rabbits with unilateral carotid occlusion induced cerebral ischemia. The cCBF was measured by the hydrogen clearance technique. After determination of the mean baseline cCBF, the effects of individual doses (0.1, 0.3 and I mg/kg) of citalopram or fluoxetine on the cCBF were investigated. Following the induction of an impaired cCBF, the changes in cCBF after drug treatments in this condition were likewise measured. The mean arterial blood pressure (MABP) and the heart rate (HR) from the electrocardiogram (ECG) were also determined. Neither citalopram nor fluoxetine influenced the cCBF in the control group. Fluoxetine improved the cCBF only very slightly in the ischemic animals. In contrast, all the doses of citalopram exerted pronounced and dose-dependent cCBF-increasing effects in the animals with unilateral carotid occlusion (maximal mean ACBF: 10, 16 and 27 ml/min/100 g tissue). The HR was decreased in both groups. Only citalopram treatment led to a slight MABP-decreasing effect. Besides enhancement of the serotonergic transmission in the brain, the cCBF-increasing effect of citalopram under ischemic conditions may be of benefit in post-stroke and vascular depression. PMID- 17853769 TI - Reproduction of reaching movements to memorized targets in the lack of visual control. AB - The objective of this study was to examine the precision of reaching movements to remembered target distances in the lack of visual information. Subjects were professional basketball players and nonathlete university students. The basketball players, having well-trained manual skills, performed better than the non-athlete students. Increase in the overestimation of the remembered target distances was found under the effect of fatigue. A weight load on the sliding handle caused some decrease in the errors of reaching the remembered targets. No significant gender differences were found. PMID- 17853770 TI - Effect of neonatal benzpyrene imprinting on the brain serotonin content and nocistatin level in adult male rats. AB - Single neonatal treatment (imprinting) with 20 microg benzpyrene results in significant increase of the brain serotonin level in the striatum, while in the other four regions (cortex, brainstem, hippocampus, hypothalamus) when measured in adults can be detected. The nocistatin level of cerebrospinal fluid (CSF) significantly decreases, while there is no change in the plasma nocistatin level. The results call attention to the comprehensive imprinting effect of benzpyrene, which in addition to receptorial, hormonal and sexual behavioral disturbances causes lasting differences in the brain serotonin and nocistatin levels, probably influencing mood and pain tolerance. PMID- 17853771 TI - Effects of 3 hours a week of physical activity on body fat and cardio-respiratory parameters in obese boys. AB - The prevalence of overweight or fat children and adolescents has markedly increased in Hungary during the past three decades. Among the possible factors insufficient physical activity and a relative or absolute excess of calorie intake associated to it can be regarded as the most important ones. The aim of the study was to analyse the effects of a 20-week aerobic exercise on body composition and on the exercise tested cardio-respiratory functions in 10-year old obese boys. Obesity was defined by a BMI greater than the cut-off value reported by Cole and co-workers (5) and a relative body fat content above 30% (13). Of the study group 21 volunteer children completed the program; the contrast group contained 28 obese boys. Mean calendar age was 10.03 +/- 0.26 in the study group (S) and 9.88 +/- 0.29 in the control group (C). The members of group S had two curricular physical education (PE) classes a week and three extracurricular aerobic physical activity sessions of 60 min net time in the afternoon, on Mondays (swimming and water games), Wednesdays (folk dance) and Fridays (soccer). Group C had only 2 PE classes a week. Anthropometric and spiroergometric data were collected in the middle of January and June of 2004. Relative body fat content and BMI did not increase during the observation period in contrast to the significant increase of both in the control group. Peak minute ventilation, aerobic power, oxygen pulse, and running distance (performed on a treadmill) increased in group S, and did not change in group C. The program was considered successful despite that the changes in the observed physiological and physical indicators appeared to be slight. However, the 5-month elevated level of physical activity brought about such development in the physical status of the obese subjects that might be an appropriate basis for regular training. Fortunately, the cardio-respiratory functions of the investigated boys were not affected yet by obesity, consequently the really dramatic change in their further lifestyle exclusively depends on their decision. PMID- 17853772 TI - Effects of mebudipine and dibudipine, two new calcium channel blockers on voltage activated calcium currents of PC12 cells. AB - Mebudipine and dibudipine are two newly synthesized dihydropyridine (DHP) calcium channel blockers that have been shown to have considerable relaxant effects on vascular and atrial smooth muscle. The in vitro half-lives of mebudipine and dibudipine are reported to be significantly longer than that of nifedipine. In this study, we investigated the effects of mebudipine and dibudipine on voltage activated Ca2+ channels on differentiated PC12 cells and compared their potencies to amlodipine. Our results point to absence of voltage-activated Ca2+ currents in undifferentiated PC12 cells. It is also concluded that mebudipine and dibudipine, like amlodipine are L-type calcium channel blockers. When tested in a range of 10 100 microM, mebudipine is at least as potent as amlodipine in inhibition of peak Ba2+ currents in differentiated PC12 cells while dibudipine is significantly less potent compared to amlodipine and mebudipine. PMID- 17853773 TI - Attenuating effects of prior oestradiol benzoate priming on 5-HT-mediated lordosis behavior in rats are dose-dependent. AB - The present study was designed to investigate the role of the 5-HT7 receptors in lordosis and compare the lordotic responses with 5-HT1A agent under the influence of different steroid-priming regimens in ovariectomized, non-receptive and receptive rats. 8-OH DPAT, a 5-HT1A agonist and 5-CT, a 5-HT7 agonist inhibited the lordosis differently in non-receptive and receptive rats, however, the response was attenuated in a dose-dependent manner following 5-CT treatment in the first two tests. Treatment with 5-HT1A antagonist, WAY 100 135 caused a protective effect which was evident in the second test only. Priming with 25 microg OB attenuated in the first test in non-receptive rats whereas the same dose repeated a similar pattern in receptive rats. The attenuation of LQ was evident in rats treated with 5-HT7 antagonist, SB 269970-A. This finding shows that WAY 100 135, a 5-HT1A antagonist has potency to attenuate inhibitory influence of 8-OH DPAT by enhancing lordosis behavior acutely in female rats with a low estrous state. Treatment with 5-CT and SB 269970-A as 5-HT7, agonist and antagonist, respectively, have mimicked 5-HT-mediated lordotic response as moderate affinity towards 5-HT1A receptors has been reported. This offers a comparable effect on lordosis as a result of the two 5-HT agents used. PMID- 17853774 TI - Isoproterenol hydrochloride augments collagen proliferation and ATPase activity in mice soleus and EDL muscles. AB - Aim of this study is to analyze the effect of chronic administration of beta agonist isoproterenol hydrochloride (60 mg kg(-1) day(-1); 30 days) on soleus (a slow type) and extensor digitorum longus (EDL, a fast type) muscles in young mice. Isoproterenol resulted in significant increase in muscle weight to whole body weight ratio with no increase in hypertrophy index in soleus muscle. A significant increase in noncontractile protein collagen is also observed in both muscles but more prominent in soleus muscle. Collagen proliferation is also analyzed on sodium dodecyle sulphate polyacrylamide gel electrophoresis (SDS PAGE) of pepsin soluble and Cyanogen Bromide (CN Br) treated pepsin insoluble collagen. Isoproterenol remolded the myofibrillar proteins in both muscles but significant increase in myofibrillar ATPase activity occurred only in soleus muscle. It is concluded that growth stimulatory effect of isoproterenol hydrochloride is more prominent in soleus than FDL muscle. Isoproterenol augmented the proliferation of non-contractile protein collagen in soleus and EDL muscles. The transformation in myofibrillar proteins caused by isoproterenol might lead to an enhancement of contractile performance. PMID- 17853775 TI - Polymer hollow fiber-encapsulated peripheral nerve extracts change their activity towards injured hippocampal neurites in rats. AB - The regeneration of the adult mammalian central nervous system (CNS) requires changes of the nonpromising environment. Applying peripheral nerve grafts and their extracts are both the useful method to induce regeneration of injured CNS neurites. Our previous reports showed that degeneration of peripheral nerves enhanced their neurotrophic activity in a time-dependent manner. Electrophoretical analysis of proteins obtained from degenerating sciatic nerves revealed significant changes in fractions of low molecular mass. The aim of the present work was to examine the influence of fractionated extracts from 7-day predegenerated and non-predegenerated peripheral nerves upon injured hippocampal neurites in adult rats. The extracts were closed in fibrin-filled connective tissue chambers (CTC) or within CTC-wrapped polymer hollow fibers (PHF) of 30 kDa cut-off. The cell bodies of regrowing fibers were labeled with FITC-HRP. The CTCs appeared to be useful tool for implantation of artificial grafts into mammalian CNS. Full-spectrum nerve extracts induced strong regeneration of injured hippocampal neurites. The number of labeled cells within hippocampus was significantly lower in PHF groups than in CTC ones, indicating that low-mass proteins present in peripheral nerve extracts are not sufficient to induce successful regeneration. PMID- 17853776 TI - Beta-agonists enhance the lactic dehydrogenase (LDH) expression in serum and ventricular myocytes of mice. AB - Beta-agonists have skeletal muscle specific protein anabolic effects and are also known to cause cardiac hypertrophy. Changed total LDH and its isozymic patterns are conveniently employed for the detection of different pathophysiological states of the tissues. The purpose of this study is to confirm total LDH and its isozymic expression in ventricular tissue and serum in mice following oral administration of single but higher dose of isoproterenol (Iso) and clenbuterol (Cl) (100 mg/kg body wt. and 20 mg/kg body wt., respectively), after 4, 8 and 20 hours of drug administration. Mice heart witnessed increased total LDH levels with time. Serum on the other hand showed decline in total LDH concentrations at the initial points of the drug treatment. No doubt, total LDH expression increased towards 20th h post-drug treatment but this increase is mainly due to anaerobic isozymes, i.e. LDH4 and LDH5. The findings of the present study suggest that tissue damage is definitely caused by two beta-agonists after giving single dose for shorter time span (20 hours) and the impact of the damage varies from drug to drug. Increase in total LDH in serum is not due to release from heart but from some other tissues having anaerobic metabolism. PMID- 17853777 TI - The genotoxicity study of garlic and pasipy herbal drops by peripheral blood micronucleus test. AB - The in vivo rodent micronucleus test is widely used as a genotoxic assay to detect the clastogenic activity of chemicals. In this research the genotoxic effects of herbal drops of garlic and pasipy were evaluated using the micronucleus test. Maximum Tolerated Dose (MTD) was determined by a dose-response test. For each medicine three treatment groups were considered with doses of MTD, 1/2 MTD and 1/4 MTD according to the CSGMT protocol (1995 Japan). Drugs were administered orally to mice (test groups). Mitomicin C was used as a known genotoxic agent in positive control group. The peripheral blood samples before treatment (zero time samples) were considered as negative control. The appearance of a micronucleus is used as an index for genotoxic potential. The results obtained indicated that the herbal drops showed genotoxicity effect and it was dose-dependent compared to the negative control group. This genotoxicity was significant (p < 0.05) but the genotoxic effects of garlic and pasipy were "not significant" compared to the historical negative control group (p > 0.05). Therefore our results if compared to the negative control group is significant and it is worthy of consideration. PMID- 17853778 TI - Overweight and obesity in 7 to 10-year-old Hungarian boys. Short communication. AB - Increasing prevalence of overweight and obesity is a serious social and health problem both in the economically developed and developing countries. Despite this fact the nation-wide growth studies completed in Hungary during the past 30 years had not categorised the children either by body fat content or nutritional status. The aim of the study was to estimate the prevalence of overweight and obese boys in the country at the beginning of the new millennium. Height, body mass and four skinfold thicknesses were measured in 7173 volunteer boys aged between 7 and 10 and living in various urban and rural settlements of Hungary between 2003 and 2005. Nutritional status was qualified by the BMI and relative body fat content. The significantly increasing prevalence with age of overweight and obesity ranged between 10.3 and 23.4%. The results showed the joint effects of a secular trend of growth and of a remarkably changed lifestyle. Of these the consequences of the lifestyle are the more important ones. The high and possibly further increasing prevalence of child-age overweight and obesity reminds one of the observations of Kopp and associates (5), namely that of the increased prevalence of chronic childhood diseases during the past 15 years. More intense habitual physical activity and dramatic changes in dietary habits still promise some solution. No one should reckon, however, with the efficiency of physical education at the schools with its very few classes. PMID- 17853779 TI - Physiological considerations about a statement by Gaius Petronius. AB - In my inauguration speech on November 8, 1989 as Rector of the Karl-Franzens University in Graz (1) I have warned not to split off the Medical Faculty as a separate Medical University "... since such a separation of a part of a University corresponds to an amputation." In spite of this and of other warnings the decision was made by a federal law to permit this separation. The irrevocable and definite step to execute the separation was done by a vote of the Medical Faculty in Graz. The logical consequence is now the development of isolationism, which will lead to a narrowness of Medicine in a kind of "Splendid Isolation." The observation of systems like a University shows, that in such a community time, time course and periods play an important role. It seems interesting to discuss the time course of the development of Universities from the first foundations in Europe and to analyze the effect of sudden changes produced by external influences. In particular the new laws, which came into effect in the last decades and years and changed the function of the Universities markedly, are of interest. From a discussion of the development of Universities until recent events one can conclude, that the splitting of each of the three Austrian Universities, which included Medical Faculties, into a new Medical University and a Rest University will lead to the growth of two "daughter cells" with each growing to a larger size than the former whole University. Another conclusion indicates that even in simpler systems instability can be produced, if new disturbing inputs are effective in a too fast sequence. PMID- 17853780 TI - Comments to the paper "Physiological considerations about a statement by Gaius Petronius. PMID- 17853781 TI - [Iron deficiency anemia in adults. Main symptoms: fatigue, pallor, (stress-) dyspnea, headache, concentration disorders]. PMID- 17853782 TI - [Kissing osteochondroma of the lower limb]. AB - As definition, a "kissing" osteochondroma is a typical new bony formation with erosion on the adjacent paired bone, provoked by pressure of the outgrowth. Further diagnostics for incidentally diagnosed solitary osteochondroma should be performed only in cases where malignant transformation is suspected. PMID- 17853783 TI - [MRI-based diagnosis of an acute bilateral compartment syndrome]. AB - The acute compartment syndrome describes a posttraumatic or inflammatory edema, which leads to a painful constraint of muscular movement and paresthesia. An increase in pressure in the anatomical compartment is postulated. The main symptoms include local swelling, sensory loss, local muscle weakness as well as late livid discoloration. Therapy of choice is an early fasciotomy with decompression to avoid serious complications like muscle necrosis. Here we report a 22 year old patient who postoperatively suffered from a bilateral paresis of the foot jack. Further examinations by electromyography and magnetic resonance imaging (MRI) led to the diagnosis of an acute bilateral compartment syndrome. PMID- 17853784 TI - [Bronchitis, pregnancy test and hematuria--an atypical algorithm for diagnosis]. AB - A 42-year old housewife presented herself with flu symptoms and dry cough. Because of pregnancy test (chest x-ray) we accidentally detected a hematuria. Exact medical history revealed the presence of a known IgA-Nephropathy. Banal respiratory infections can exacerbate IgA Nephropathy. In addition, medical history and further investigations are important because of possible secondary IgA-Glomerulonephritis. Treatment of IgA glomerulopathy depends on blood pressure, renal function and degree of proteinuria. An acute renal insufficancy is uncommon (< 5%), but 25% patients develop during 20-25 years a terminal insufficandy. PMID- 17853785 TI - ["Is my brother's life in the institution still safe? Or one day he gets "pneumonia" (...) and we get the urn???)" [1]--The relatives of institution patients during National-Socialism patient killing action "T4"]. PMID- 17853786 TI - [Molecular evolution of dengue virus: a necessary field of research]. AB - Dengue is a viral disease present in tropical developing countries where cause an important number of new cases annually. There are four serotypes (DENV-1 to 4), which can cause a clinical spectrum varying from a mild disease; dengue fever, to a potential life-threatening form; dengue hemorrhagic fever (DHF). The molecular mechanism to explain the developing of DHF remains uncertainly, but it has been related to previous immunity to a different serotype, host-depending factors (age, nutritional status, HLA type) and to viral genotypes. In this sense, have been described a number of genotypes among the serotypes, some of which has been associated with increased severity. In Venezuela, since 1989 have been reported cases due to all the viral serotypes, but there are few studies attempting to determine the genotype circulating in both epidemic and endemic situations. In all the reports, Venezuelan isolates are related to Asian genotypes, some of which have been associated with high risk to develop DHF. It is necessary more studies to analyze the whole viral genome from isolates collected in last years, in order to get information about how and why occur the viral extinction process in epidemics settings, its geographical origin and if certainly there are genotypes associated with DHF circulating in the country. Despite its importance to public health, it is necessary more research to understand deeply the dengue physiopathology. Genomics seems to be an important tool to achieve this objective and to help to develop required therapeutics and prophylactic strategies in a short time. PMID- 17853787 TI - [Enterobius vermicularis in preschool children from a suburban area in San Felix, Bolivar State, Venezuela]. AB - To determine the enterobiosis prevalence in preschool children, a study was carried out from may-july 2003, in the SEU "Teresa de la Parra" in San Felix, Bolivar State, Venezuela. Three samples from the perianal region were obtained from every child, by applying the Graham method, and one sample was obtained of the subungucal deposit by scraping and cutting off their finger nails. These samples were preserved in 10% formol and processed by the formol-ether method. Also, a stool sample was collected and analyzed by direct examination and the formol-ether method. The prevalence of Enterobius vermicularis was 45.8% (27/59). No differences in relation to age (chi2 = 1.23 d. f. = 2) and sex (p > 0.05) were observed between the infected children. The eggs E. vermicularis were not observed in the 59 samples of subungueal deposits. In conclusion, although the enterobiosis prevalence was high, as determined by the Graham method, a relationship could not be found between E. vermicularis in the scotch tape and the finger nail samples of the children evaluated. PMID- 17853788 TI - [Zinc levels in prostatic fluid of patients with prostate pathologies]. AB - The prostate is a gland that surrounds the posterior urethra in man and, along with seminal vesicles, produces prostatic and seminal fluids. Prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer are the most frequent pathologies of this gland. Zinc is an important element in the makeup of prostatic fluid and plays an important role in the immunology of the infectious and neoplastic pathologies of the prostate. The aim of this study was to determine zinc concentrations in prostatic fluid of patients with prostate pathologies and to use this measurement as a diagnostic parameter. Thirty patients with prostatic pathologies and ten healthy controls were studied. Prostatic fluid samples were collected using prostatic massage. Zinc concentration was determined using electrothermal atomizeratomic absorption spectrometry (ETA-AAS). The mean zinc concentrations obtained in the studied population were as follows: 11 patients with BPH: 15.087,78 micromol/dL, 10 patients with prostatis: 863,33 micromol/dL, 9 patients with prostate cancer: 1.027,60 micromol/dL and 10 healthy subjects: 7.467,52 micromol/dL. The low zinc concentrations obtained in patients with prostatitis and prostate cancer, in contrast to the control group, led us to consider the possibility of recommending zinc supplements as a coadjuvant therapy in patients with prostatitis and also, to use zinc measurements as another diagnostic tool, for cases in which it is necessary to differentiate benign prostatic hyperplasia from prostate cancer. PMID- 17853789 TI - Development of a Lepto-IgM EIACR test to diagnose leptospirosis disease in Costa Rican patient samples. AB - Leptospirosis is an endemic disease throughout Costa Rica, which could be misdiagnosed because manifestations of this febrile disease may vary from mild flu-like symptoms to severe illness involving vital organs such as liver and lungs. Therefore an early specific diagnosis is important to ensure a favorable clinical outcome. The purpose of this study was to develop a Leptospira sp. anti IgM EIA (Lepto-IgM EIACR) test and to compare it using Lepto-Dipstick IgM (Lepto DS IgM) and PanBio-EIA IgM with the Microscopy Agglutination test (MAT) as a reference assay. Sera from 736 healthy blood donors were used as negative controls to calculate specificity (97.1%), Confidence Interval 95 (CI (96-98). Cross reactivity was evaluated in 268 patient samples with 6 different diseases. Dengue and measles had the highest cross reactivity (16%) while rubella showed the lowest (3%). To determine the sensitivity of the Lepto- IgM EIACR, 33 samples positive by MAT of 96 paired samples from patients with symptoms related to leptospirosis infection were tested. Lepto-IgM EIACR reached a sensitivity of 90.9% (CI 81-100), while Lepto-DS IgM was 48.5% (CI (31-66). The most frequent serovars detected by MAT in these paired samples were Hebdomadis 14.7%, Hardjo 11.8%, Pomona 8.8% and Icterohaemorrhagiae 5.9%. Furthermore 59 febrile patient samples were tested initially with PanBio-EIA IgM, 21 samples (35%) were positive. When these samples were re-tested by Lepto-IgM EIACR and Lepto-DS IgM, 80.9% and 33% were positive, respectively. The results of the evaluation indicate that Lepto-IgM EIACR test could be a good alternative to detect acute leptospirosis in Costa Rica. PMID- 17853790 TI - Mercury in hair as a biomarker of exposure in a coastal Venezuelan population. AB - To assess mercury exposure and potential risk, total mercury (THg-H) and methylmercury (MeHg-H) in hair were studied in 160 adults. The study group consisted of 60 individuals living in the north central coast of Venezuela. A section of the area was known to be contaminated with mercury from a chlor-alkali plant installed near one of the tributary rivers of the Caribbean Sea. The study group was selected from 4 inclusion criteria points. The control group was composed of 100 individuals selected from Carabobo state with no known exposure to Hg. A questionnaire was designed to collect demographic, health information, work activities and fish consumption habits. Hair samples were analyzed for THg. Samples with THg-H > 5 microg/g were also analyzed for MeHg. The mean THg-H was 1.88 +/- 1.50 and 0.99 +/- 0.87 microg/g for the study and control groups, respectively. The study group was statistically higher than control individuals, however, no statistical differences of THg-H were found between each of the 4 categories of both groups. Mean MeHg-H value was 3.67 +/- 1.25 microg/g. Associations were made between Hg-H and several variables. No significant relationship was noted between Hg-H levels and clinical symptoms. R analyses and t-tests were used to determine associations between questionnaire variables and THg-H. The main predictors of THg-H levels in the study group were fish consumption and frequency. As both groups presented relatively low values for THg H and MeHg-H, the results of this study indicate that Hg exposure did not exceed safe levels. However, a more in-depth exposure assessment should be conducted to more accurately assess this exposure, specifically in terms of Hg content in water and fish sampling. PMID- 17853791 TI - [Serum values of interleukin-10, gamma-interferon and vitamin A in female adolescents]. AB - Many studies have demonstrated that vitamin A deficiency (VAD) affects the immunomodulated response mediated by cytokines. However, these studies are controversial. The purpose of the present study was to analyze Interleukin-10, gamma-Interferon and vitamin A serum concentrations in adolescents. Seventy three female, not pregnant adolescents (15.95 +/- 1.10 years old), of a low socioeconomic condition were studied. Serum retinol was determined by HPLC using the Bieri method. International reference standards were considered to define VAD (serum retinol < 20 microg/dL), risk of VAD (20-30 microg/dL) and vitamin A sufficiency (>30 microg/dL). Serum concentrations of Interleukine-10 (IL-10) and gamma-Interferon (gamma-IFN) were detected by an ELISA method (pg/mL). The data were analyzed using the SAS/STAT statistical program; the results were presented as mean +/- Standard deviation and the differences between mean values were analyzed by the ANOVA test. The prevalence of VAD in adolescents was 6.85% (serum retinol <20 microg/dL) and 41.10% adolescents had VAD risk (20-30 microg/dL). Adolescents with VAD showed a significant increase of gamma-IFN serum concentration (p = 0.01). Correlation between serum retinol and gamma-IFN was r = -0.29 (p = 0.01). Adolescents represent a VAD risk group. Low serum levels of retinol were correlated with high levels of gamma-IFN, this cytokine has been associated with chronics inflammatory processes and it can contribute to increase the morbidity and mortality in this population. PMID- 17853792 TI - [Social stratification and nutritional anthropometry in children under 15 years old La Escalera, Lara State, Venezuela]. AB - Malnutrition is a public health problem for underdeveloped countries. From the 852 million of undernourished estimated by FAO between 2000 and 2002, 815 million belonged to underdeveloped countries, 28 million to countries in transition and 9 million to developed countries. Malnutrition in Venezuela had a 6% raise between 2000 and 2002, when it went from 11% to 17%. This work was done with children under 15 years old from La Escalera, using classic indicators and their combination, relating them with socioeconomic conditions, through the NBI and Graffar Mendez Castellano methods, as to consider the population nutritional profile. The higher prevalence corresponded to normal nutritional values, which oscillated between 55,7% and 80,7% in the 7-14 years old group and the 2-6 years old group, respectively. Malnutrition was found in the under 2 years old group and 7-14 years old group, with values ranging between 12,5 and 41,0% respectively. The least prevalence was found for excess malnutrition. 100% of the families in this study are poor, according to NBI; although the Graffar Mendez Castellano method established that poverty was about 60%, while 40% belonged to a medium-low status. Relating nutritional diagnosis with social stratification and the mother's educational level, three patterns were observed: III, IV and V, prevailing normal diagnosis, followed by malnutrition by deficit and malnutrition by excess, respectively. The predominating mother's educational level corresponded to incomplete high school, followed by analphabetism and the least prevalent has complete basic elementary education. It should be noted that the nutrition deficit was inversely related to the socioeconomic stratification and the mother's educational level. PMID- 17853793 TI - [Adrenocortical function in patients with systemic mycoses]. AB - The systemic mycoses like paracoccidioidomycosis and histoplasmosis, are the main cause of adrenal insufficiency in the countries where they arc endemic. In Venezuela an elevated frequency of these mycoses has been registered. The objective of this study was to evaluate the glucocorticoid adrenal function in patients with paracoccidioidomycosis and histoplasmosis hospitalized in the University Hospital "Ruiz y Pacz" of Ciudad Bolivar (Bolivar state) and in the Hospital "Luis Felipe Rojas Guevara", of El Tigre (Anzoategui state), Venezuela, between January 2003 and January 2004. The test of fast stimulation with synthetic adrenocorticotrophin hormone (ACTH) was applied to a total of 12 patients with diagnosis of some of these mycoses and data of epidemiologic interest were taken. The proportion men:women was of 5:1, the average age was 35.1 +/- 0.37 years, similar to the control group. Basal plasmatic cortisol levels were within the normal rank in all the patients. After the injection of synthetic ACTH, an increase of plasmatic cortisol values in the same rank for patients with a normal adrenal function was observed, but it was significantly lower than the observed for the control group. These results suggest that there is an adrenal gland functional reserve diminution in patients with either Paracoccidioidomycosis or Histoplasmosis. In patients with systemic mycoses, it is important to evaluate the response to the test of fast stimulation with ACTH due to the frequency of impairment of the glucocorticoid adrenal function in our location. PMID- 17853794 TI - On the anticonvulsant activity of kaurenic acid. AB - Kaurenic acid [(-)-kaur-16-en-19-oic acid] is a diterpene isolated from the aerial parts of Espeletia semiglobulata, one of 85 species of Espeletiinae found in Venezuela. Its anticonvulsive activity was studied using two different models of experimental seizures: spinal seizures induced by sudden cooling (SSSC) in amphibians and seizures induced by pentylenetetrazol (PTZ) in mice. In SSSC, kaurenic acid (KA) inhibited the tonic hind-limb extension with an ED50 of 2.5 mg/kg. It was 4-fold more potent than known anticonvulsant drugs such as carbamazepine and phenytoin and 100-fold more potent than valproic acid. However, KA as well as valproic acid were ineffective against the clonic phase of SSSC. In the PTZ-induced seizures, KA at doses of 0.625 and 1.25 mg/kg increased the latency of seizure onset and protected against generalized clonic-tonic seizures by 45% and 65%, respectively. The sedative effects of KA had an ED50 of 8.5 mg/kg in mice and 75 mg/kg in amphibians. This work provides experimental evidence supporting the potential value of kaurenic acid as an anticonvulsive drug. PMID- 17853795 TI - [Trichotillomania: three cases presentation and diagnosis tests review]. AB - Trichotillomania represents a chronic disorder in which patients traumatically remove their own hair in a bizarre pattern. Like obsessive-compulsive disorder, the hair-pulling behavior is recognized as senseless and undesirable, but is performed in response to several emotions and affects, such as increasing anxiety, or unconscious conflicts with a resultant tension relief. The condition may be episodic, but is usually chronic and difficult to treat. We present three cases of trichotillomania and review common clinical and pathologic findings of this, often chronic and socially debilitating, disorder. In addition, we discuss treatment options for dermatologists and how the collaboration with psychiatrists is the most effective management for these difficult-to-treat patients. PMID- 17853796 TI - [Tissue engineering and construction of human skin in vitro]. AB - Tissue engineering is the new science that has come to make possible the growth of new organ tissue from small fragments of healthy tissue, thus partially or totally restoring the lost functions of ill tissues or organs, as shown by the achievements made with the culture of skin, cornea or cartilage. Thus far, this new science is able to ensure the recovery of lost functions and, doubtlessly, in a near future will be capable of developing tissues and organs not unlike natural ones. In our laboratory we have began the development of tissue engineering techniques for the successful construction of in vitro skin with the aim at mid term of producing cornea and cartilage. In a first clinical trial, these techniques were applied in the treatment of chronic skin lesions and the advantages and reach of these new tools were demonstrated for the effective solution of problems with would otherwise not be easily solved through the use of conventional treatments. PMID- 17853797 TI - Translating exercise biology into the Venezuelan medical education and health care system. AB - In the absence of pharmacological agents, physical exercise was widely used by physicians in the late 19th century to treat a number of maladies. In the 1950's, epidemiological evidence suggested an association between physical activity and health, and increased interest in clinical exercise biology. By the 1990's, sufficient research data was accumulated on the benefits of exercise, such that North American medical associations, government agencies, and the World Health Organization have published guidelines on exercise for public and clinical populations. Despite this, leaders in medical education have remained reluctant to incorporate exercise biology into the core medical curriculum, or to systematically implement it in graduate medical education. This work reviews Venezuelan exercise biology literature, and its medical applications. Venezuelan scientists and clinicians have invested efforts in cardiopulmonary exercise testing, skeletal muscle adaptations to training and exercise cardiovascular pharmacology in patients, sedentary subjects and athletes. It is suggested here, that there is a need to develop education and research programs in basic and clinical exercise biology in the formal training of medical students, physicians in residency programs, and allied health care professionals. Tentative steps to initiate this process are proposed. PMID- 17853798 TI - [Lysine dendrimers as vectors for delivering genetic constructs to eukaryotic cells]. AB - Asymmetrical lysine dendrimers are promising as vectors for delivering gene expression constructs into mammalian cells. The condensing, protective, and transfection properties were studied for pentaspherical lysine dendrimer D5 and its analog D5C10, modified with capric acid residues at the outer sphere; in addition, the transfection activity was assayed for complexes DNA-dendrimer endosomolytic peptide JTS-1. Fatty acid residues incorporated in lysine dendrimers proved to improve their ability to bind DNA, to protect DNA from nuclease degradation, and to ensure its transfer into the nucleus. Peptide JTS-1 introduced in DNA-dendrimer complexes significantly increased their transfection activity. The potentiating effect of JTS-1 was especially high with the DNA-D5C10 complex. An excess of JTS-1 changed the structure of the complexes and reduced their transfection activity. It was assumed that dendrimers D5 and D5C10 are promising vectors for delivering DNA to eukaryotic cells and provide a basis for constructing more refined nonvirus module carriers. PMID- 17853799 TI - [Localization of the NotI clones from human chromosome 3 on quail microchromosomes]. AB - For the purpose of comparative mapping of quail (Coturnix c. japonica) and human (Homo sapiens) genomes, DNA fragments from human chromosome 3 (HSA3p14-21 and HSA3q13-23) were localized on quail mitotic chromosomes. Using the method of double-color fluorescence DNA-DNA in situ hybridization, these fragments were mapped to two different microchromosomes. Earlier, similar studies were performed using chicken mitotic chromosomes. There it was demonstrated that the clones of interest were distributed among three microchromosomes (GGA12, GGA14, and GGA15). Thus, interspecific difference in the location of human chromosome 3 DNA fragments in the genomes of closely related avian species was discovered. A new confirmation of the hypothesis on the preferable localization of the gene-rich human chromosome regions on avian microchromosomes was obtained. At the same time, a suggestion on the localization of some orthologous genes in the genome of the organism under study was made: ARF4, SCN5A, PHF7, ABHD6, ZDHHC3, MAPKAPK3, ADSYNA (homolog of chicken chromosome 12), DRD2, PP2C-ETA, RAB7, CCKAR, and PKD1 (homolog of chicken chromosome 15). However, localization of the corresponding quail genes needs to be confirmed, as far as the sequences used were only the orthologs of the corresponding chicken genes. PMID- 17853800 TI - [Mutagenic effect of the rocket fuel component asymmetric dimethylhydrazine on rats of various ages]. AB - Mutagenic effect of asymmetric dimethylhydrazine (ADMH) on rats of different age groups upon acute and subacute treatment and protective effect of a Limonium gmelinii preparation. Genotoxic effect of ADMH depending on the dose and duration of treatment was established. The phytopreparation lacked mutagenicity and toxicity and had a protective effect in combination with the xenobiotic. PMID- 17853801 TI - [A comparative cytogenetic study of the tetraploid oat species with the A and C genomes: Avena insularis, A. magna, and A. murphyi]. AB - Differential C-banding of chromosomes and in situ hybridization with the probes pTa71 and pTa794 were used for a comparative cytogenetic study of the three tetraploid oat species with the A and C genomes: Avena insularis, A. magna, and A. murphyi. These species were similar in the structure and patterns of C-banding of several chromosomes as well as in the location of the loci 5S rRNA genes and main NOR sites; however, they differed in the number and localization of minor 45S rDNA loci as well as in the morphology and distribution of heterochromatin in some chromosomes. According to the data obtained, A. insularis is closer to A. magna, whereas A. murphyi is somewhat separated from these two species. Presumably, all the three studied species originated from the same tetraploid ancestor, and their divergence is connected with various species-specific chromosome rearrangements. The evolution of A. murphyi is likely to have occurred independently of the other two species. PMID- 17853802 TI - Studying genetic diversity in the core germplasm of confectionary sunflower (Helianthus annuus L.) in China based on AFLP and morphological analysis. AB - Characterization of germplasm resources of confectionary sunflower is critical to assess collection diversity and enhance utilization which is few referred. 70 germplasm representing 12 provinces of China was characterized using 8 amplified fragment length polymorphic (AFLP) primers and 17 morphological descriptors. Euclidean distance were used for AFLP and morphological data ranged from 0.32 to 1.56 and from 0.30 to 1.48 respectively. No two germplasm had a distance of zero, showing there were no duplicate entries. Cluster analysis of AFLP data were determined by SAS which 70.0% of the total germplasm (49 entries) were including in the two main clusters I and II. A wild germplasm was single in the end cluster which is at 1.56 distance level to other clusters. For morphological data, 75.7% of the germplasm (53 entries) were in two main clusters II and III. This clustering pattern for AFLP and morphological data suggested unique germplasm were generally under represented in the collection. The morphological-based clusters showed some locality separation by germplasm origin, but in general, origin did not correspond closely with the clustering pattern. Principal component analysis (PCA) showed the first seven principal components accounted for 81.33% of the total variation, of which 43.05% was contributed by the first two principal components. PMID- 17853803 TI - [Intraspecific divergence in wheats of the Timopheevi group as revealed by in situ hybridization with tandem repeats of the Spelt1 and Spelt52 families]. AB - Fluorescent in situ hybridization (FISH) was used to study the distribution of the Spelt1 and Spelt52 repetitive DNA sequences on chromosomes of ten accessions representing three polyploid wheat species of the Timopheevi group: Triticum araraticum (7), T. timopheevii (2), and T. kiharae (1). Sequences of both families were found mostly in the subtelomeric chromosome regions of the G genome. The total number of Spelt1 sites varied from 8 to 14 in the karyotypes of the species under study; their number, location, and size differed among the seven T. araraticum accessions and were the same in the two T. timopheevii accessions and T. kiharae, an amphidiploid T. timopheevii-Aegilops tauschii hybrid. The Spelt52 tandem repeat was detected in the subtelomeric regions of chromosomes 1-4; its sites did not coincide with the Spelt1 sites. The chromosome distribution and signal intensity of the Spelt52 repeats varied in T. araraticum and were the same in T. timopheevii and T. kiharae. The chromosome distributions of the Spelt1 and Spelt52 repeats were compared for the polyploid wheats of the Timopheevi group and diploid Ae. speltoides, a putative donor of the G genome. The comparison revealed a decrease in hybridization level: both the number of sites per genome and the size of sites were lower. The decrease was assumed to result from repeat elimination during polyploidization and subsequent evolution of wheat and from the founder effect, since the origin of Timopheevi wheats might involve the genotype of Ae. speltoides, which is highly polymorphic for the distribution of Spelt1 and Spelt52 sequences and is similar in the chromosome location of the repeats to modern wheat. PMID- 17853804 TI - [Mitochondrial DNA variation pattern in larches of Eastern Siberia and the Far East]. AB - Genetic variation has been studied in 32 Eastern Siberian and Far Eastern populations of Larix Mill. with the use of three mitochondrial markers based on polymerase chain reaction. Eight multilocus haplotypes with a heterogeneous spatial distribution (G(ST) = 0.788, N(ST) = 0.829) have been found, which indicates limited gene flows between populations. Several geographic regions with specific larch haplotype sets have been determined: (1) Japan, (2) southern Sakhalin and the Kuril Islands, (3) Primor'e and Korea, (4) Kamchatka, and (5) Eastern Siberia and the northern Far East. The haplotype fixed in the Kamchatka is absent in the Magadan oblast or Chukotka but is present in southern Primor'e and Sakhalin Island. This may be explained by either the postglacial recolonization of Kamchatka by larch that spread from Primor'e through Sakhalin and the Kuril Islands or its survival through the last glacial maximum in the Kamchatka Peninsula. The biogeography of larch and other woody plants indicate that boreal species have a common history of the colonization of Kamchatka. PMID- 17853805 TI - [Cytogenetic characterization of Solanum lycopersicoides Dun. alien chromosome additions in cultivated tomato]. AB - Cytogenetic analysis of five Solanum lycopersicoides monosomic alien addition lines of tomato was carried out. Meiotic analysis showed that additional chromosomes caused serious abnormalities. It was demonstrated that different chromosomes of S. lycopersicoides had different effects on chromosome pairing. For instance, associations formed between chromosomes II and IV of S. lycopersicoides and chromosomes of cultured tomato were trivalents, while chromosome XI in all cells was present as a univalent. Pachytene analysis showed that chromosomes of homeologous group II paired at their long arms, and their nucleolus organizer regions were of different sizes. The use of molecular markers provided accelerated identification of the introgression of S. lyvcopersicoides genetic material. PMID- 17853806 TI - [Sex chromosomes at early meiosis in three wood mice species of the genus Apodemus (Rodentia, Muridae)]. AB - The prophase of the first meiotic division was studied in field mice of the species Apodemus (Sylvaemus) flavicollis, A. (S.) ponticus, and A. (S.) uralensis by light and electron microscopy. The karyotypes of the species were described on the base of electron microscopy of synaptonemal complexes in spermatocytes I. The axial elements of the sex chromosomes at early-middle pachytene can synapse along the major portion of the Y axis; at late pachytene-early diplotene, the synapsis region shrinks; and at diakinesis-metaphase I, X and Y chromosomes associate tail to-tail in all species studied. The behavior of sex chromosomes in the synapsis in the species studied was quite uniform. The results are discussed in the context of earlier data on the behavior of sex chromosomes in various rodent species in meiosis prophase I and their banding. PMID- 17853807 TI - [Genetic variation and differentiation in striped field mouse Apodemus agrarius inferred from RAPD-PCR analysis]. AB - Genetic variation and differentiation of the trans-Palearctic species Apodemus agrarius (striped field mouse), whose range consists of two large isolates European-Siberian and Far Eastern-Chinese, were examined using RAPD-PCR analysis. The material from the both parts of the range was examined (41 individual of A. agrarius from 18 localities of Russia, Ukraine, Moldova, and Kazakhstan); the Far Eastern part was represented by samples from the Amur region, Khabarovsk krai, and Primorye (Russia). Differences in frequencies of polymorphic RAPD loci were found between the European-Siberian and the Far Eastern population groups of striped field mouse. No "fixed" differences between them in RAPD spectra were found, and none of the used statistical methods permitted to distinguish with absolute certainty animals from the two range parts. Thus, genetic isolation of the European-Siberian and the Far Eastern population groups of A. agrarius is not strict. These results support the hypothesis on recent dispersal of striped field mouse from East to West Palearctics (during the Holocene climatic optimum, 7000 to 4500 years ago) and subsequent disjunction of the species range (not earlier than 4000-4500 years ago). The Far Eastern population group is more polymorphic than the European-Siberian one, while genetic heterogeneity is more uniformly distributed within it. This is probably explained by both historical events that happened during the species dispersal in the past, and different environmental conditions for the species in different parts of its range. The Far Eastern population group inhabits the area close to the distribution center of A. agrarius. It is likely that this group preserved genetic variation of the formerly integral ancestral form, while some amount of genetic polymorphism could be lost during the species colonization of the Siberian and European areas. To date, the settlement density and population number in general are higher than within the European-Siberian isolate, which seems to account for closer interpopulation associations, intense genetic exchange, and "smoothing" of polymorphism within the Far Eastern population group of A. agrarius. PMID- 17853808 TI - [Population structure of rural settlements of Sakha Republic (Yakutia): surname structure]. AB - The distributions of surnames have been studied in 12 rural ethnic territorial groups of Sakha Republic (Yakutia). The populations studied are characterized by considerable accumulation of individual surnames, the surname spectra of representative of different ethnic groups living in the same area substantially overlapping. The random isonymy, migration index, surname diversity, and the surname distribution redundancy index display geographic and ethnic differences. The isonymy relationship coefficients calculated for representatives of individual ethnic groups (Yakuts, Evens, and Russians) and for total populations of the settlements studied are determined by the geographic distances between the compared populations and the intensity of migrations. PMID- 17853809 TI - Glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) polymorphisms in a sample of the population in Northern Italy. AB - Glutathione S-transferase is a group of multifunctional enzymes important in the metabolism of xenobiotics. GSTT1 and GSTM1 are polymorphic in human populations. Since a relation between polymorphism and cancer susceptibility has been found, their distribution in human populations is of great interest. In the present study the distribution of GSTT1 and GSTM1 genotypes was studied in a total sample of 252 individuals of three localities of north-west Italy (Postua, Cavaglia and Biella) by PCR test. The frequencies of GSTT1 and GSTM1 "null" genotypes were respectively 7.94% and 34.92%. There are no significant differences between the populations studied in the GSTT1 "null" genotypes. On the other hand, for GSTM1 the frequency of gene deletion in Postua (25.5%) differs significantly (p < 0.01; chi-square test) from that of Biella (46.32%), which approaches the values indicated by most studies for Europeans (about 50%). The analysis of the frequencies of GSTT1 and GSTM1 polymorphisms among different age groups showed a lower frequency of negative genotypes in the older group, although not statistically confirmed. PMID- 17853810 TI - [New efficient extragenic microsatellite markers for hemophilia A carrier state diagnostics]. AB - In search of new efficient markers for genetic diagnostics of hemophilia A, two tri-nucleotide microsatellite repeats (STR) at chromosome X loci, which flank coagulation factor VIII gene (F8), namely STR HA472--CTT-repeat, which is localized adjacent to the GAB3 gene 163 bp apart from the 3' end of the F8 gene and STR HA544--repeat (CTT)x(ATT)y located at a distance of 375 bp from the 5' end of the F8 gene were discovered. Detailed analysis using PCR and sequencing has shown that STR HA472 contains two long variable CTT-blocks separated by small spacer CCTCCC. The location of recognition site of restriction endonuclease Mnl1 (CCTC) in the spacer permits to test differentially the polymorphic blocks and thus to increase the analysis informativity. STR HA544 is also represented by two polymorphic blocks (CTT and ATT), for separate amplification of which highly informative PCR amplification assays were elaborated. The study has been done using DNA samples of 212 individuals (125 women) from 48 families with hemophilia A carriers. Our results point to Mendelian inheritance of the markers studied, a high number of allelic variants and high heterozygosity, which was 90% and 100% for HA544 and HA472, respectively. This permitted us to use these data for practical gene diagnostics of the carriers and prenatal diagnostics of hemophilia A. In addition to high informativity STR HA472 and HA544 are highly important for diagnostics as they are located at a shorter distance than other known extragenic polymorphisms of the F8 gene. In contrast to dinucleotide repeats, trinucleotide repeats are readily tested, not requiring high-resolution electrophoretic systems. In addition, they are located on the opposite sites of the F8 gene. This permits to control homologous recombination events in the locus and thus to prevent diagnostic mistakes. PMID- 17853811 TI - [The gene pool of the Belgorod region population: I. Differentiation of all district populations based on anthroponymic data]. AB - The gene pool of the entire population of all the 21 raions (districts) of the Belgorod oblast (region) has been studied using anthroponymic data. Considerable geographic variations of the number of surnames and the degree of population subdivision (0.00003 < f(r)* < 0.00125) in the 21 districts have been demonstrated. Districts with low population subdivision levels are mainly located in the central and southwestern raions of the Belgorod oblast, contain an urbanized area (city), and border on Ukraine (they are characterized by a considerable Ukrainian immigration). Urbanization significantly affects the population structure of the Belgorod oblast. In urbanized districts, rural populations lack the relationships between the population size, number of surnames, and population subdivision level (f(r)). PMID- 17853812 TI - Molecular analysis of Y chromosome microdeletions in idiopathic cases of male infertility in Serbia. AB - The aim of this study was to detect frequency of microdeletions of Y chromosome in idiopathic cases of male infertility in Serbian population. Patients were subjected to detailed clinical, endocrinological and cytogenetic examinations. Ninety patients with normal cytogenetic findings with azoospermia and severe oligozoospermia were included in the study. In these patients microdeletion analysis was performed by multiplex polymerase chain reaction (PCR) method on DNA extracted from peripheral blood. In each case 6 markers in azoospermia factor (AZF) regions were tested: sY84, sY86 (AZFa); sY127, sY134 (AZFb); sY254, sY255 (AZFc). Deletions on Y chromosome were detected in 14 of 90 cases (15.6%), 9 with azoospermia and 5 with severe oligozoospermia. Of total number of 17 deletions, 11 (64.7%) were detected in AZFc region, 3 (17.6%) in AZFa region and 3 (17.6%) in AZFb region. Microdeletions in AZF region of Y chromosome, especially AZFc microdeletions, represent common genetic cause of idiopathic azoospermia and severe oligozoospremia in Serbian infertile men. Therefore, testing for Y chromosome microdeletions should be considered as an important element in diagnosis and genetic counseling of infertile men in Serbia and decisions regarding the assisted reproduction should be made based on the presence and type of AZF microdeletions. PMID- 17853813 TI - [Local honeybee (Apis mellifera mellifera L.) populations in the Urals]. AB - The COI-COII intergenic region of mitochondrial DNA (mtDNA) was studied in local honeybee (Apis mellifera mellifera) L. populations from the Middle and Southern Urals. Analysis of bee colonies in these regions revealed apiaries enriched in families descending from A. m. mellifera in the maternal lineage. These results confirm the suggestion of preservation of A. m. mellifera refuges in the Urals and provide grounds for work on the preservation of the gene pool of this bee variety, valuable for all Russia. PMID- 17853814 TI - [Mutations altering the specificity of the sensor RNA encoded by the Bacillus subtilis pbuE gene]. AB - Site-directed mutagenesis was used to study the leader region of the Bacillus subtilis pbuE gene, which codes for adenine-specific sensor RNA. Two nucleotide substitutions, 70U --> C and A100 --> G, in the conserved region (A box) of the leader changed the specificity of the sensor RNA in vivo: guanine acted as a positive transcription effector in place of adenine. PMID- 17853815 TI - [The regional cerebral blood flow pattern of the normal human brain and its factorial structure]. PMID- 17853816 TI - [Brain bioelectrical activity in humans with high anxiety level]. PMID- 17853818 TI - [Biofeedback for the optimization of psychomotor reactivity: Communication I. Comparative analysis of biofeedback and common performance practice]. PMID- 17853817 TI - [Intrahemispheric coherence of the EEG depending on clinical manifestations of temporal epilepsy in children]. PMID- 17853819 TI - [Characteristic features of microvascular responses of healthy humans to simulated psychoemotional stress]. PMID- 17853820 TI - [Reflection of the pattern of skin vascular responses (dermographism) in the verbal expression of sensations in healthy subjects]. PMID- 17853821 TI - [Characteristics of immunological parameters in 10- to 14-year-old healthy children with different activity of the emotional motivational behavior systems]. PMID- 17853823 TI - [Spectral and spectral-temporal heart rate analysis in newborn children]. PMID- 17853822 TI - [Immunological reactivity in children with central nervous system injuries immunized with ADS-M and measles vaccines]. PMID- 17853824 TI - [Respiratory sinus arrhythmia as an objective criterion for evaluation and optimization speech respiration parameters]. PMID- 17853825 TI - [Motor and autonomic asymmetries in athletes with different specializations and nonathletes: Communication II]. PMID- 17853826 TI - [Characteristics of age-related dynamics in the activity of the human motor system]. PMID- 17853827 TI - [Central mechanisms of fatigue during local static muscular activity]. PMID- 17853828 TI - [Physiological characteristics of system quanta of athletic performance]. PMID- 17853829 TI - [The effect of leptin on the microbiocidal activity of monocytes in humans]. PMID- 17853830 TI - [Functional training status of soccer players from leading teams in Russia]. PMID- 17853831 TI - [Structural and functional characteristics of the heart of professional soccer players after retirement from long-term sport activity]. PMID- 17853832 TI - [Changes in parameters of humoral immunity in patients with acute lung abscesses in the course of ultraviolet phototherapy]. PMID- 17853834 TI - [Influence of the unified state examination on the functional state in high school students]. PMID- 17853833 TI - [Physiological, emotional, and professional adaptation of students in the medical schools]. PMID- 17853835 TI - Blogging on drugs. PMID- 17853836 TI - Gitmo: should doctors force-feed prisoners? PMID- 17853837 TI - The puzzle of hidden ability. PMID- 17853838 TI - After Virginia Tech. PMID- 17853839 TI - A new twist on yoga. PMID- 17853840 TI - Om work. PMID- 17853841 TI - When newborn babies have to die...perinatal palliative care? PMID- 17853842 TI - Transition towards end of life in palliative care: an exploration of its meaning for advanced cancer patients in Europe. AB - Transition as a concept in healthcare has been explored, but there is limited empirical work which considers transition in the context of palliative care, specifically from the patient perspective. This article reports findings from a qualitative study designed to explore transition experiences of 100 advanced cancer patients in six European countries. Data were analyzed using the ATLAS.ti program. Findings suggest that transition is a confusing time of mixed messages, poor communication, and uncertainty, but the physical environment of the hospice offers a place of ontological security from which to address this. Transition concepts fail to capture the palliative care experience fully. Transience, as an alternative concept, is reported, although further research is needed to explore this. In clinical practice, the value given to hospice by patients suggests that clinicians must carefully balance the benefit of mainstream integration with sensitive assimilation of hospice philosophy. PMID- 17853843 TI - Psychometric properties of a modified version of the Caregiver Reaction Assessment Scale measuring caregiving and post-caregiving reactions of caregivers of cancer patients. AB - Most care received by cancer patients is provided in the community by informal or unpaid caregivers. The unrelenting care demands can lead to physical, emotional, social, and financial reactions; furthermore, studies indicate that the effects of caregiving may endure after the patient's death. A need therefore exists for instruments measuring both caregiving and post-caregiving reactions. Among available instruments, the Caregiver Reaction Assessment (CRA) is a multidimensional, 5-factor measure designed to assess the negative and positive aspects of caregiving. The current study examined the psychometric properties and factor structure of responses to a modified Hebrew version of the CRA aimed at measuring caregiving and post-caregiving reactions. Although the scale was modified, it was assumed that, similar to the original CRA, a 5-factor structure would be supported by means of confirmatory factor analysis. A total of 236 bereaved primary caregivers of cancer patients from central and southern regions of Israel were recruited over a period of 18 months. As hypothesized, results provide support for a 5-factor structure of responses to this modified version of the CRA. The concurrent validity of responses to the scale was also supported. Replication of the findings with randomly derived and larger sample sizes is needed. PMID- 17853844 TI - Conceptualizations of dying by an elderly man. PMID- 17853845 TI - A systematic review of prognostic tools for estimating survival time in palliative care. PMID- 17853846 TI - Building primary care capacity in palliative care: proceedings of an interprofessional workshop. PMID- 17853847 TI - Continuity of care for advanced cancer patients: comparing the views of spousal caregivers in Ontario, Canada, to Dumont et al.'s theoretical model. PMID- 17853848 TI - Take your EHR with you. PMID- 17853849 TI - Patient e-mail perils. PMID- 17853850 TI - Employed doctors: know your rights. PMID- 17853851 TI - A doctor who's open every day. PMID- 17853852 TI - An effective way to use assistants. PMID- 17853853 TI - What drug rep visits cost you. PMID- 17853854 TI - Doctors are getting more tech savvy. PMID- 17853855 TI - Malpractice: to settle or fight. PMID- 17853856 TI - Islands of life. A warmer world creates a new iceberg ecology. PMID- 17853857 TI - The boys are all right. PMID- 17853858 TI - Matters of morality. Americans have always disagreed passionately when science and religion come into conflict. PMID- 17853859 TI - Summer ease. PMID- 17853860 TI - Monitoring lymphocyte proliferation in vitro and in vivo with the intracellular fluorescent dye carboxyfluorescein diacetate succinimidyl ester. AB - This protocol outlines the carboxyfluorescein diacetate succinimidyl ester (CFSE) method for following the proliferation of human lymphocytes in vitro and mouse lymphocytes both in vitro and in vivo. The method relies on the ability of CFSE to covalently label long-lived intracellular molecules with the highly fluorescent dye, carboxyfluorescein. Following each cell division, the equal distribution of these fluorescent molecules to progeny cells results in a halving of the fluorescence of daughter cells. The CFSE labeling protocol described, which typically takes <1 h to perform, allows the detection of up to eight cell divisions before CFSE fluorescence is decreased to the background fluorescence of unlabeled cells. Protocols are outlined for labeling large and small numbers of human and mouse lymphocytes, labeling conditions being identified that minimize CFSE toxicity but maximize the number of cell divisions detected. An important feature of the technique is that division-dependent changes in the expression of cell-surface markers and intracellular proteins are easily quantified by flow cytometry. PMID- 17853861 TI - Measuring lymphocyte proliferation, survival and differentiation using CFSE time series data. AB - Cellular proliferation is an essential feature of the adaptive immune response. The introduction of the division tracking dye carboxyfluorescein diacetate succinimidyl ester (CFSE) has made it possible to monitor the number of cell divisions during proliferation and to examine the relationship between proliferation and differentiation. Although qualitative examination of CFSE data may be useful, substantially more information about division and death rates can be extracted from quantitative CFSE time-series experiments. Quantitative methods can reveal in detail how lymphocyte proliferation and survival are regulated and altered by signals such as those received from co-stimulatory molecules, drugs and genetic polymorphisms. In this protocol, we present a detailed method for examining time-series data using graphical and computer-based procedures available to all experimenters. PMID- 17853862 TI - A protocol for designing siRNAs with high functionality and specificity. AB - Effective gene silencing by the RNA interference (RNAi) pathway requires a comprehensive understanding of the elements that influence small interfering RNA (siRNA) functionality and specificity. These include (i) sequence space restrictions that define the boundaries of siRNA targeting, (ii) structural and sequence features required for efficient siRNA performance, (iii) mechanisms that underlie nonspecific gene modulation and (iv) additional features specific to the intended use (i.e., inclusion of native sugar or base chemical modifications for increased stability or specificity, vector design, etc.). Attention to each of these factors enhances siRNA performance and heightens overall confidence in the output of RNAi-mediated functional genomic studies. Here, we provide a detailed protocol explaining the methodologies used for manual and web-based design of siRNAs. PMID- 17853863 TI - Measurement of chronic oxidative and inflammatory stress by quantification of isoketal/levuglandin gamma-ketoaldehyde protein adducts using liquid chromatography tandem mass spectrometry. AB - Measurement of F(2)-isoprostanes (F(2)-IsoPs) has been independently verified as one of the most reliable approaches to assess oxidative stress in vivo. However, the rapid clearance of F(2)-IsoPs makes the timing of sample collection critical for short-lived oxidative insults. Isoketals (IsoKs) are gamma-ketoaldehydes formed via the IsoP pathway of lipid peroxidation that rapidly react with lysyl residues of proteins to form stable protein adducts. Oxidative stress can also activate cyclooxygenases to produce prostaglandin H(2), which can form two specific isomers of IsoK-levuglandin (LG) D(2) and E(2). Because adducted proteins are not rapidly cleared, IsoK/LG protein adduct levels can serve as a dosimeter of oxidative and inflammatory damage over prolonged periods of time as well as brief episodes of injury. Quantification of IsoK/LG protein adducts begins with liquid-phase extraction to separate proteins from lipid membranes, allowing measurement of both IsoK/LG protein adducts and F(2)-IsoP from the same sample if desired. IsoK/LG-lysyl-lactam adducts are measured by liquid chromatography tandem mass spectrometry after proteolytic digestion of extracted proteins, solid-phase extraction and preparative HPLC. PMID- 17853864 TI - Competitive PCR for precise nucleic acid quantification. AB - The exact quantification of tiny amounts of nucleic acids in biological samples continues to remain a requirement in both the experimental and the diagnostic laboratory. Competitive PCR involves the coamplification of a target DNA sample with known amounts of a competitor DNA that shares most of the nucleotide sequence with the target; in this way, any predictable or unpredictable variable affecting PCR amplification has the same effect on both molecular species. Competitive PCR therefore permits the quantification of the absolute number of target molecules in comparison to the amount of competitor DNA. Although requiring intensive post-PCR manipulation, the accuracy of competitive PCR by far exceeds that of any other quantitative PCR procedure, including real-time PCR. This protocol covers all stages in the competitive PCR and RT-PCR methods, from the design and construction of competitor molecules, and the competitive PCR itself, to the analysis of data and quantification of target DNA. Once the correct primers are available, the protocol can be completed in about 24 h. PMID- 17853865 TI - Preparation and use of metal surface-immobilized DNA hairpins for the detection of oligonucleotides. AB - The following protocol describes the experimental steps used to prepare arrayable and label-free biological sensors that are based on the fluorescence unquenching of DNA hairpins immobilized on metal surfaces. This two-part protocol describes both the creation of gold-coated substrates and the oligonucleotide surface self assembly process that transforms the substrates into reporters for detecting DNA. Using this procedure, one can create sensors for oligonucleotides that are highly sensitive and have demonstrated an exceptional specificity to single nucleotide polymorphisms. From start to finish, the entire procedure can be accomplished in 24-30 h. PMID- 17853866 TI - Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. AB - Permeability coefficients across monolayers of the human colon carcinoma cell line Caco-2, cultured on permeable supports, are commonly used to predict the absorption of orally administered drugs and other xenobiotics. This protocol describes our method for the cultivation, characterization and determination of permeability coefficients of xenobiotics (which are, typically, drug-like compounds) in the Caco-2 model. A few modifications that have been introduced over the years are incorporated in the protocol. The method can be used to trace the permeability of a test compound in two directions, from the apical to the basolateral side or vice versa, and both passive and active transport processes can be studied. The permeability assay can be completed within one working day, provided that the Caco-2 monolayers have been cultured and differentiated on the permeable supports 3 weeks in advance. PMID- 17853867 TI - Detection of protein-protein interactions using a simple survival protein fragment complementation assay based on the enzyme dihydrofolate reductase. AB - Biochemical 'pathways' are systems of dynamically assembling and disassembling protein complexes, and thus, much of modern biological research is concerned with how, when and where proteins interact with other proteins involved in biochemical processes. The demand for simple approaches to study protein-protein interactions, particularly on a large scale, has grown recently with the progress in genome projects, as the association of unknown with known gene products provides one crucial way of establishing the function of a gene. It was with this challenge in mind that our laboratory developed a simple survival protein fragment complementation assay (PCA) based on the enzyme dihydrofolate reductase (DHFR). In the DHFR PCA strategy, two proteins of interest are fused to complementary fragments of DHFR. If the proteins of interest interact physically, the DHFR complementary fragments are brought together and fold into the native structure of the enzyme, reconstituting its activity, detectable by the survival of cells expressing the fusion proteins and growth in selective medium. Using the protocol described here, the survival selection can be completed in one to several days, depending on the cell type. PMID- 17853868 TI - Inhibitor fingerprinting of metalloproteases using microplate and microarray platforms: an enabling technology in Catalomics. AB - One of the most fundamental properties of an enzyme is its selectivity, a property that has proved highly challenging to understand. Recent developments offer methodologies to rapidly establish activity-dependent profiles of enzymes. In this protocol, we describe methods to elucidate inhibitor fingerprints of enzymes. By taking advantage of well-defined small-molecule inhibitor libraries and the screening throughput offered from microplate and microarray platforms, we provide step-by-step application of the methodology toward the global characterization of metalloproteases, an important class of enzymes involved in numerous diseases and cellular processes. The same strategy is nonetheless applicable to virtually any given enzyme class, provided suitable experimental design and chemical inhibitor libraries are carefully implemented. We are able to routinely fingerprint as many as 2,000 independent enzyme interactions on the microplate platform within a span of approximately 7 h; however, the same throughput is attained within 5 h on the microarray platform. PMID- 17853869 TI - Preparation of large RNA oligonucleotides with complementary isotope-labeled segments for NMR structural studies. AB - RNA structure determination by solution NMR spectroscopy is often restricted to small RNAs (<15 kDa) owing to the problem of chemical shift degeneracy. A fruitful coupling of novel NMR techniques with segmental RNA labeling methodologies could be a powerful tool to overcome the molecular mass limitation of RNA NMR spectroscopy. Herein, we describe a time- and cost-effective procedure to prepare and purify segmentally labeled large RNAs. Two sets of RNA fragments with complementary labeling schemes, such as one fragment (13)C- and the other (15)N-labeled, are prepared by in vitro transcription from a single plasmid DNA. The desired RNA fragments are excised from the primary transcript by two cis acting hammerhead ribozymes, yielding the required engineered ends for subsequent, complementary ligation. The resulting RNA oligonucleotides display NMR spectra with greatly reduced resonance overlap and thus enable NMR studies of smaller labeled RNA segments within the native context of a large RNA. The procedure is expected to take 3-4 weeks to implement. PMID- 17853870 TI - Application of cationic conjugated polymers in microarrays using label-free DNA targets. AB - A fluorescence-based microarray technique that does not require target DNA labeling is detailed. This 'label-free' approach utilizes a cationic, water soluble conjugated polymer PFBT (poly[9,9'-bis(6''-(N,N,N trimethylammonium)hexyl)fluorene-co-alt-4,7-(2,1,3-benzothiadiazole) dibromide]), and neutral PNA (peptide nucleic acid) hybridization probes. DNA hybridization to immobilized PNA spots results in a change in the net charge at that particular surface. Electrostatic interactions between the cationic polymer and negatively charged DNA bind the polymer to the hybrid DNA/PNA complex. By exciting the conjugated polymer at 488 nm on a commercial microarray scanner, the presence of the target is directly indicated by the fluorescence emission of the polymer. This feature eliminates the necessity of target labeling required in traditional microarray protocols. There are five steps involved in the procedure before scanning or imaging the array: (i) slide hydration, (ii) target hybridization, (iii) post-hybridization washing, (iv) polymer application and (v) polymer washing. Each step takes 20 min to 1 h. The overall protocol requires approximately 2-3 h. PMID- 17853871 TI - A computational method of prediction of the end-diastolic pressure-volume relationship by single beat. AB - The end-diastolic pressure-volume relation (EDPVR) is an important descriptor of passive cardiac pump properties. However, clinical utility has been limited by the need for measurement of pressures and volumes over relatively large ranges. In this protocol, we describe an algorithm to estimate the entire EDPVR in humans from a single measured pressure-volume (P-V) point. This algorithm was developed from observations made from accurately measured EDPVRs of human hearts, which indicated that when normalized by appropriate left ventricular volume scaling (to arrive at volume-normalized EDPVRs, EDPVR(n)) EDPVR(n)s were nearly identical in all patients. In this protocol, we demonstrate how to use EDPVR(n)s to predict a second P-V point on the EDPVR, in which case the entire EDPVR can then be predicted. With recent advances for accurate noninvasive measurement of end diastolic pressure and volumes, this protocol permits the assessment of passive properties in a broader range of research and clinical settings. PMID- 17853872 TI - Detergent resistance as a tool in membrane research. AB - The biological membrane is a complicated matrix wherein different lipid environments are thought to exist. The more ordered or raft environment has been perceived biochemically accessible via its relative resistance to detergent. This paper outlines the protocols developed in our laboratory for the analysis of such detergent-resistant membranes (DRMs). We stress the fact that DRMs are artifactual in nature and should not be equivocated to lipid rafts, their usefulness being limited to assigning raft-association potential most convincingly when changes in DRM composition are induced by biochemically/physiologically relevant events. These protocols are completed in 1 2 d. PMID- 17853873 TI - A protocol for imaging alternative splicing regulation in vivo using fluorescence reporters in transgenic mice. AB - Imaging technologies are influencing the way we study regulatory processes in vivo. Several recent reports use fluorescence minigenes to image alternative splicing events in living cells and animals. This type of reporter is being used to generate transgenic mice to visualize splicing regulation in diverse tissues and cell types. In this protocol, we describe how to develop animals that report on alternative splicing and how to assess reporter expression in excised organs and tissue sections. The entire procedure, from making the reporters to imaging organs and tissues in adult transgenic mice, should take approximately 1.5 years. Fluorescence reporters can be used to image many splicing decisions in normal tissues and organs and can be extended to the study of disease states. PMID- 17853874 TI - Facile synthesis of Ag nanocubes and Au nanocages. AB - This protocol describes a method for the synthesis of Ag nanocubes and their subsequent conversion into Au nanocages via the galvanic replacement reaction. The Ag nanocubes are prepared by a rapid (reaction time < 15 min), sulfide mediated polyol method in which Ag(I) is reduced to Ag(0) by ethylene glycol in the presence of poly(vinyl pyrrolidone) (PVP) and a trace amount of Na(2)S. When the concentration of Ag atoms reaches supersaturation, they agglomerate to form seeds that then grow into Ag nanostructures. The presence of both PVP and Na(2)S facilitate the formation of nanocubes. With this method, Ag nanocubes can be prepared and isolated for use within approximately 3 h. The Ag nanocubes can then serve as sacrificial templates for the preparation of Au nanocages, with a method for their preparation also described herein. The procedure for Au nanocage preparation and isolation requires approximately 5 h. PMID- 17853875 TI - Atomic force microscopy and spectroscopy of native membrane proteins. AB - Membrane proteins comprise 30% of the proteome of higher organisms. They mediate energy conversion, signal transduction, solute transport and secretion. Their native environment is a bilayer in a physiological buffer solution, hence their structure and function are preferably assessed in this environment. The surface structure of single membrane proteins can be determined in buffer solutions by atomic force microscopy (AFM) at a lateral resolution of less than 1 nm and a vertical resolution of 0.1-0.2 nm. Moreover, single proteins can be directly addressed, stuck to the AFM stylus and subsequently unfolded, revealing the molecular interactions of the protein studied. The examples discussed here illustrate the power of AFM in the structural analysis of membrane proteins in a native environment. PMID- 17853876 TI - Enzymatic ligation assisted by nucleases: simultaneous ligation and digestion promote the ordered assembly of DNA. AB - This protocol describes a method for the one-tube preparative-scale assembly of a specific DNA molecule, the enzymatic ligation assisted by nucleases (ELAN) technique. DNA fragments in ligation reactions are capable of combining to produce numerous products. The ELAN method uses judicious choice of restriction enzyme sites coupled with simultaneous digestion and ligation reactions to create just one product, by converting off-pathway products back into substrate. The experimental parameters critical for a successful ELAN reaction are discussed, and the ordered, one-tube assembly of four DNA fragments in the presence of eight restriction enzymes is demonstrated. This technique will be useful to those performing gene construction, DNA computing, biophysics and even standard molecular cloning. Starting with reactant fragments, the protocol takes 4-16 h to produce nanogram to microgram yields, depending on the complexity of the reaction. PMID- 17853877 TI - Isolation of intact RNA from cytometrically sorted Saccharomyces cerevisiae for the analysis of intrapopulation diversity of gene expression. AB - Characterizing and understanding the functional heterogeneity in a given population on the cellular and molecular level is a great challenge in microbiology. Each microorganism contributes differently to the overall performance of the community and responds differently to changing microenvironmental conditions. Here, we present a method for isolation of intact RNA out of small subpopulations of live Saccharomyces cerevisiae cells for differential gene expression analysis. The protocol includes fluorescence staining, flow cytometric analysis and sorting of live yeast cells, subsequent isolation of RNA from the resulting subpopulations and finally RNA quantification and integrity check. The isolated RNA can be transcribed into cDNA and successfully used for microarray analysis. This aids in relating molecular regulation processes within subpopulations with the dynamics and functioning of the entire population. The procedure can be accomplished in 2 d. PMID- 17853878 TI - The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. AB - Differential scanning fluorimetry (DSF) is a rapid and inexpensive screening method to identify low-molecular-weight ligands that bind and stabilize purified proteins. The temperature at which a protein unfolds is measured by an increase in the fluorescence of a dye with affinity for hydrophobic parts of the protein, which are exposed as the protein unfolds. A simple fitting procedure allows quick calculation of the transition midpoint; the difference in the temperature of this midpoint in the presence and absence of ligand is related to the binding affinity of the small molecule, which can be a low-molecular-weight compound, a peptide or a nucleic acid. DSF is best performed using a conventional real-time PCR instrument. Ligand solutions from a storage plate are added to a solution of protein and dye, distributed into the wells of the PCR plate and fluorescence intensity measured as the temperature is raised gradually. Results can be obtained in a single day. PMID- 17853879 TI - Rapid solid-phase synthesis of a calmodulin-binding peptide using controlled microwave irradiation. AB - A rapid and efficient microwave-assisted solid-phase synthesis method for the preparation of a nonapeptide using conventional Fmoc/Bu(t) orthogonal protection strategy is described. In this protocol, the coupling steps are performed within 5 min at 60 degrees C and the Fmoc-deprotection steps are completed within 3 min at 60 degrees C using a dedicated single-mode microwave peptide synthesizer utilizing temperature-controlled conditions. It is demonstrated that the model nonapeptide (containing the calmodulin-binding octapeptide sequence) is synthesized in a shorter time (approximately 3.5 h) and with high purity (>95%) under microwave irradiation conditions in comparison with a reference peptide that is obtained by standard methods at room temperature (within 11 h). PMID- 17853880 TI - Isolation of DNA from small amounts of elephant ivory. AB - This protocol describes a method for the extraction of DNA from elephant ivory. These techniques are being used to assign geographic origin to poached ivory by comparing the ivory genotype to a geographic-based gene frequency map, developed separately. The method has three components: ivory pulverization, decalcification and DNA extraction. Pulverization occurs in a freezer mill while the sample is deep frozen in liquid nitrogen, preventing degradation of DNA during the process. Decalcification involves repeated agitation of the sample in 0.5 M ethylenediaminetetraacetic acid over a 4-d period. Extraction follows a modified Qiagen protocol for the extraction of DNA from animal tissue. This method can be used on all forms of ivory. However, DNA recovery is highest when the outermost layer of the tusk, the cementum, is used. When applied to extract DNA from 11 samples, in duplicate, the entire protocol can be completed in 6 d, although much of this time consists of pause points that do not require effort. The protocol provides 0.8 +/- 0.11 ng microl(-1) (mean +/- s.e., n = 48) of DNA per sample. PMID- 17853881 TI - Estimation of nuclear DNA content in plants using flow cytometry. AB - Flow cytometry (FCM) using DNA-selective fluorochromes is now the prevailing method for the measurement of nuclear DNA content in plants. Ease of sample preparation and high sample throughput make it generally better suited than other methods such as Feulgen densitometry to estimate genome size, level of generative polyploidy, nuclear replication state and endopolyploidy (polysomaty). Here we present four protocols for sample preparation (suspensions of intact cell nuclei) and describe the analysis of nuclear DNA amounts using FCM. We consider the chemicals and equipment necessary, the measurement process, data analysis, and describe the most frequent problems encountered with plant material such as the interference of secondary metabolites. The purpose and requirement of internal and external standardization are discussed. The importance of using a correct terminology for DNA amounts and genome size is underlined, and its basic principles are explained. PMID- 17853882 TI - Design and implementation of high-throughput RNAi screens in cultured Drosophila cells. AB - This protocol describes the various steps and considerations involved in planning and carrying out RNA interference (RNAi) genome-wide screens in cultured Drosophila cells. We focus largely on the procedures that have been modified as a result of our experience over the past 3 years and of our better understanding of the underlying technology. Specifically, our protocol offers a set of suggestions and considerations for screen optimization and a step-by-step description of the procedures successfully used at the Drosophila RNAi Screening Center for screen implementation, data collection and analysis to identify potential hits. In addition, this protocol briefly covers postscreen analysis approaches that are often needed to finalize the hit list. Depending on the scope of the screen and subsequent analysis and validation involved, the full protocol can take anywhere from 3 months to 2 years to complete. PMID- 17853883 TI - DNA methylation analysis by pyrosequencing. AB - Pyrosequencing is a sequencing-by-synthesis method that quantitatively monitors the real-time incorporation of nucleotides through the enzymatic conversion of released pyrophosphate into a proportional light signal. Quantitative measures are of special importance for DNA methylation analysis in various developmental and pathological situations. Analysis of DNA methylation patterns by pyrosequencing combines a simple reaction protocol with reproducible and accurate measures of the degree of methylation at several CpGs in close proximity with high quantitative resolution. After bisulfite treatment and PCR, the degree of each methylation at each CpG position in a sequence is determined from the ratio of T and C. The process of purification and sequencing can be repeated for the same template to analyze other CpGs in the same amplification product. Quantitative epigenotypes are obtained using this protocol in approximately 4 h for up to 96 DNA samples when bisulfite-treated DNA is already available as the starting material. PMID- 17853884 TI - Changing medium and passaging cell lines. AB - Cell lines are widely used in biomedical research. This protocol describes the methods used routinely to change the medium and passage the cells. Medium changes keep the cells healthy by providing fresh nutrients, while cell passage or splitting is required to maintain cells in exponential growth. Despite the simplicity of the methods used, each cell line has idiosyncracies. Whether working with one or several cell lines, there is no substitute for knowledge of their needs, including the range of phenotypes and growth patterns under different physical and nutrient conditions. Given the necessary care and attention, most cell lines are easy to maintain and grow. PMID- 17853885 TI - Fluorescence detection of protein clusters in individual cells and tissue sections by using toponome imaging system: sample preparation and measuring procedures. AB - This protocol details sample preparation and measurement procedures for a fluorescence technology capable of colocalizing hundreds of different proteins in a cell or tissue section. The procedure relies on fixation of samples and on the use of dye-conjugated tag libraries. To colocalize proteins, a sample is placed on the microscope stage of an imaging system (toponome imaging system (TIS)) performing sequential cycles of tag-dye incubation, imaging and bleaching to generate images for each localization cycle. TIS overcomes the spectral limitations of traditional fluorescence microscopy. Image processing reveals toponome maps, uncovering the coexistence of proteins at a location (protein clusters). The approach provides direct insight into the topological organization of proteins on a proteomic scale for the first time. If, for example, two dyes are used per cycle, 18 proteins in 4 visual fields can be colocalized in 21 h. Parallel TIS procedures using more than two dyes per cycle enhance the throughput. PMID- 17853886 TI - Simultaneous detection of apoptosis and mitochondrial superoxide production in live cells by flow cytometry and confocal microscopy. AB - Annexin V and Sytox Green are widely used markers to evaluate apoptosis in various cell types using flow cytometry and fluorescent microscopy. Recently, a novel fluoroprobe MitoSOX Red was introduced for selective detection of superoxide in the mitochondria of live cells and was validated for confocal microscopy and flow cytometry. This protocol describes simultaneous measurements of mitochondrial superoxide generation with apoptotic markers (Annexin V and Sytox Green) by both flow cytometry and confocal microscopy in endothelial cell lines. The advantages of the described flow cytometry method over other cell based techniques are the tremendous speed (1-2 h), exquisite precision and the possibility of simultaneous quantitative measurements of mitochondrial superoxide generation and apoptotic (and other) markers, with maximal preservation of cellular functions. This method combined with fluorescent microscopy may be very useful to reveal important spatial-temporal changes in mitochondrial superoxide production and execution of programmed cell death in virtually any cell type. PMID- 17853887 TI - Using the beta-lactamase protein-fragment complementation assay to probe dynamic protein-protein interactions. AB - We have developed a general experimental strategy that enables the quantitative detection of dynamic protein-protein interactions in intact living cells, based on protein-fragment complementation assays (PCAs). In this method, protein interactions are coupled to refolding of enzymes from cognate fragments where reconstitution of enzyme activity acts as the detector of a protein interaction. We have described a number of assays with different reporter readouts, but of particular value to studies of protein interaction dynamics are assays based on enzyme reporters that catalyze the creation of products, thus taking advantage of the amplification of signal afforded. Here we describe protocols for one such PCA based on the enzyme TEM beta-lactamase as a reporter in mammalian cells. The beta lactamase PCA consists of fusing complementary fragments of beta-lactamase to two proteins of interest. If the proteins interact, the fragments are brought together and fold into active beta-lactamase. Here we describe a protocol for this PCA that can be completed in a few hours, using two different substrates that are converted to fluorescent or colored products by beta-lactamase. PMID- 17853888 TI - Regulation of nicotinic receptor trafficking by the transmembrane Golgi protein UNC-50. AB - Nicotinic acetylcholine receptors (AChRs) are pentameric ligand-gated ion channels that mediate fast synaptic transmission at the neuromuscular junction (NMJ). After assembly in the endoplasmic reticulum (ER), AChRs must be transported to the plasma membrane through the secretory apparatus. Little is known about specific molecules that mediate this transport. Here we identify a gene that is required for subtype-specific trafficking of assembled nicotinic AChRs in Caenorhabditis elegans. unc-50 encodes an evolutionarily conserved integral membrane protein that localizes to the Golgi apparatus. In the absence of UNC-50, a subset of AChRs present in body-wall muscle are sorted to the lysosomal system and degraded. However, the trafficking of a second AChR type and of GABA ionotropic receptors expressed in the same muscle cells is not affected in unc-50 mutants. These results suggest that, in addition to ER quality control, assembled AChRs are sorted within the Golgi system by a mechanism that controls the amount of cell-surface AChRs in a subtype-specific way. PMID- 17853889 TI - Elongation factor 1a mediates the specificity of mitochondrial tRNA import in T. brucei. AB - Mitochondrial tRNA import is widespread in eukaryotes. Yet, the mechanism that determines its specificity is unknown. Previous in vivo experiments using the tRNAs(Met), tRNA(Ile) and tRNA(Lys) have suggested that the T-stem nucleotide pair 51:63 is the main localization determinant of tRNAs in Trypanosoma brucei. In the cytosol-specific initiator tRNA(Met), this nucleotide pair is identical to the main antideterminant that prevents interaction with cytosolic elongation factor (eEF1a). Here we show that ablation of cytosolic eEF1a, but not of initiation factor 2, inhibits mitochondrial import of newly synthesized tRNAs well before translation or growth is affected. tRNA(Sec) is the only other cytosol-specific tRNA in T. brucei. It has its own elongation factor and does not bind eEF1a. However, a mutant of the tRNA(Sec) expected to bind to eEF1a is imported into mitochondria. This import requires eEF1a and aminoacylation of the tRNA. Thus, for a tRNA to be imported into the mitochondrion of T. brucei, it needs to bind eEF1a, and it is this interaction that mediates the import specificity. PMID- 17853890 TI - Rumble in the nuclear jungle: compartmentalization, trafficking, and nuclear action of plant immune receptors. AB - Plants and animals have evolved structurally related innate immune sensors inside cells to detect the presence of microbial molecules. An evolutionary ancient folding machinery becomes engaged for the synthesis of autorepressed receptor forms in both kingdoms. The receptors act as regulatory signal transduction switches and are activated upon direct or indirect perception of non-self structures. Recent findings indicate that nucleo-cytoplasmic partitioning and nuclear activity is critical for the function of several plant immune sensors, thereby linking receptor function to transcriptional reprogramming of host cells for pathogen defense. This implies short signalling pathways and reveals parallels with regulatory control mechanisms of animal steroid receptors. PMID- 17853891 TI - The coupling of synthesis and partitioning of EBV's plasmid replicon is revealed in live cells. AB - Epstein-Barr virus (EBV) is an exceptionally successful human viral pathogen maintained as a licensed, plasmid replicon in proliferating cells. We have measured the distributions of EBV-derived plasmids in single live cells throughout the cell cycle in the absence of selection and confirmed the measured rates of duplication and partitioning computationally and experimentally. These analyses have uncovered a striking, non-random partitioning for this minimalist plasmid replicon and revealed additional properties of it and its host cells: (1) 84% of the plasmids duplicate during each S phase; (2) all duplicated plasmids are spatially colocalized as pairs, a positioning that is coupled to their non random partitioning; (3) each clone of cells requires a certain threshold number of plasmids per cell for its optimal growth under selection; (4) defects in plasmid synthesis and partitioning are balanced to yield wide distributions of plasmids in clonal populations of cells for which the plasmids provide a selective advantage. These properties of its plasmid replicon underlie EBV's success as a human pathogen. PMID- 17853892 TI - Direct stimulation of receptor-controlled phospholipase D1 by phospho-cofilin. AB - The activity state of cofilin, which controls actin dynamics, is driven by a phosphorylation-dephosphorylation cycle. Phosphorylation of cofilin by LIM kinases results in its inactivation, a process supported by 14-3-3zeta and reversed by dephosphorylation by slingshot phosphatases. Here we report on a novel cellular function for the phosphorylation-dephosphorylation cycle of cofilin. We demonstrate that muscarinic receptor-mediated stimulation of phospholipase D1 (PLD1) is controlled by LIM-kinase, slingshot phosphatase as well as 14-3-3zeta, and requires phosphorylatable cofilin. Cofilin directly and specifically interacts with PLD1 and upon phosphorylation by LIM-kinase1, stimulates PLD1 activity, an effect mimicked by phosphorylation-mimic cofilin mutants. The interaction of cofilin with PLD1 is under receptor control and encompasses a PLD1-specific fragment (aa 585-712). Expression of this fragment suppresses receptor-induced cofilin-PLD1 interaction as well as PLD stimulation and actin stress fiber formation. These data indicate that till now designated inactive phospho-cofilin exhibits an active cellular function, and suggest that phospho-cofilin by its stimulatory effect on PLD1 may control a large variety of cellular functions. PMID- 17853893 TI - Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis. AB - TSG101 and ALIX both function in HIV budding and in vesicle formation at the multivesicular body (MVB), where they interact with other Endosomal Sorting Complex Required for Transport (ESCRT) pathway factors required for release of viruses and vesicles. Proteomic analyses revealed that ALIX and TSG101/ESCRT-I also bind a series of proteins involved in cytokinesis, including CEP55, CD2AP, ROCK1, and IQGAP1. ALIX and TSG101 concentrate at centrosomes and are then recruited to the midbodies of dividing cells through direct interactions between the central CEP55 'hinge' region and GPP-based motifs within TSG101 and ALIX. ESCRT-III and VPS4 proteins are also recruited, indicating that much of the ESCRT pathway localizes to the midbody. Depletion of ALIX and TSG101/ESCRT-I inhibits the abscission step of HeLa cell cytokinesis, as does VPS4 overexpression, confirming a requirement for these proteins in cell division. Furthermore, ALIX point mutants that block CEP55 and CHMP4/ESCRT-III binding also inhibit abscission, indicating that both interactions are essential. These experiments suggest that the ESCRT pathway may be recruited to facilitate analogous membrane fission events during HIV budding, MVB vesicle formation, and the abscission stage of cytokinesis. PMID- 17853894 TI - Anticipating chromosomal replication fork arrest: SSB targets repair DNA helicases to active forks. AB - In bacteria, several salvage responses to DNA replication arrest culminate in reassembly of the replisome on inactivated forks to resume replication. The PriA DNA helicase is a prominent trigger of this replication restart process, preceded in many cases by a repair and/or remodeling of the arrested fork, which can be performed by many specific proteins. The mechanisms that target these rescue effectors to damaged forks in the cell are unknown. We report that the single stranded DNA binding (SSB) protein is the key factor that links PriA to active chromosomal replication forks in vivo. This targeting mechanism determines the efficiency by which PriA reaches its specific DNA-binding site in vitro and directs replication restart in vivo. The RecG and RecQ DNA helicases, which are involved in intricate replication reactivation pathways, also associate with the chromosomal replication forks by similarly interacting with SSB. These results identify SSB as a platform for linking a 'repair toolbox' with active replication forks, providing a first line of rescue responses to accidental arrest. PMID- 17853899 TI - Abstracts of the 37th Annual Meeting of the European Society for Dermatological Research, 5-8 September 2007, Zurich, Switzerland. PMID- 17853895 TI - Activation of the Cdc42p GTPase by cyclin-dependent protein kinases in budding yeast. AB - Cyclin-dependent kinases (CDKs) trigger essential cell cycle processes including critical events in G1 phase that culminate in bud emergence, spindle pole body duplication, and DNA replication. Localized activation of the Rho-type GTPase Cdc42p is crucial for establishment of cell polarity during G1, but CDK targets that link the Cdc42p module with cell growth and cell cycle commitment have remained largely elusive. Here, we identify the GTPase-activating protein (GAP) Rga2p as an important substrate related to the cell polarity function of G1 CDKs. Overexpression of RGA2 in the absence of functional Pho85p or Cdc28p CDK complexes is toxic, due to an inability to polarize growth. Mutation of CDK consensus sites in Rga2p that are phosphorylated both in vivo and in vitro by Pho85p and Cdc28p CDKs results in a loss of G1 phase-specific phosphorylation. A failure to phosphorylate Rga2p leads to defects in localization and impaired polarized growth, in a manner dependent on Rga2p GAP function. Taken together, our data suggest that CDK-dependent phosphorylation restrains Rga2p activity to ensure appropriate activation of Cdc42p during cell polarity establishment. Inhibition of GAPs by CDK phosphorylation may be a general mechanism to promote proper G1-phase progression. PMID- 17853900 TI - Growth of the Asian health-care market: global implications for the pharmaceutical industry. AB - The global economy is being transformed by an explosion of information unleashed by the internet, the digital revolution, communications and increased international mobility. This transformation is manifesting in many ways, including rapid development of countries such as China, commoditization of public services, mobilization of workforces, shifting of market control from suppliers to consumers, interlinked rises in product demand and customer expectations, and problems regulating international business competition. As Asia is home to half of the world's population, and offers both a large relatively low-cost workforce in some countries and a potentially huge retail market, this region could be central to the future of the global economy. Like other industries, the pharmaceutical industry faces a new array of Asia-specific opportunities and challenges. Success in meeting these challenges will go to those pharmaceutical companies that best understand the unique strengths and constraints of Asia's diverse cultures, talents and markets. PMID- 17853901 TI - Flying under the radar: the new wave of BCR-ABL inhibitors. AB - The introduction of the BCR-ABL kinase inhibitor imatinib mesylate (Gleevec; Novartis) revolutionized the treatment of chronic myeloid leukaemia (CML). However, most patients with CML receiving imatinib still harbour molecular residual disease and some develop resistance associated with ABL kinase domain mutations. The second-generation BCR-ABL inhibitors nilotinib (Tasigna; Novartis) and dasatinib (Sprycel; Bristol-Myers Squibb) have shown significant activity after imatinib failure in clinical trials, but still face similar obstacles to imatinib, including negligible activity against the frequent BCR-ABL T315I mutation and modest effects in advanced phases of CML. Various medicinal chemistry efforts, in part aided by structural studies of the ABL kinase-imatinib complex have resulted in the synthesis of a new generation of BCR-ABL inhibitors, some of which have shown encouraging preliminary activity in clinical trials, including against T315I mutants. Here, we discuss these emerging therapies, which have the potential to improve the outcome of patients with CML. PMID- 17853902 TI - Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. AB - The realization that dendritic cells (DCs) orchestrate innate and adaptive immune responses has stimulated research on harnessing DCs to create more effective vaccines. Early clinical trials exploring autologous DCs that were loaded with antigens ex vivo to induce T-cell responses have provided proof of principle. Here, we discuss how direct targeting of antigens to DC surface receptors in vivo might replace laborious and expensive ex vivo culturing, and facilitate large scale application of DC-based vaccination therapies. PMID- 17853903 TI - Calcium signalling and cell-fate choice in B cells. AB - Alterations in the cytosolic concentration of calcium ions (Ca2+) transmit information that is crucial for the development and function of B cells. Cytosolic Ca2+ concentration is determined by a balance of active transport and gradient-driven Ca2+ fluxes, both of which are subject to the influence of multiple receptors and environmental sensing pathways. Recent advances in genomics have allowed for the compilation of an increasingly comprehensive list of Ca2+ transporters and channels expressed by B cells. The increasing understanding of the function and regulation of these proteins has begun to shift the frontier of Ca2+ physiology in B cells from molecular analysis to determining how diverse inputs to cytosolic Ca2+ concentration are integrated in specific immunological contexts. PMID- 17853904 TI - A novel cytosolic class I antigen-processing pathway for endoplasmic-reticulum targeted proteins. AB - Proteins bearing an endoplasmic reticulum (ER) leader are inserted into the ER followed by cleavage of the signal peptide. Major histocompatibility complex class I-restricted T-cell epitopes can be generated from these proteins by the proteasome after retrotranslocation into the cytosol. Here, we show that an HLA A(*)0201-restricted epitope from prostate stem cell antigen contains the cleavage site of the ER signal peptidase. The resulting cleavage products fail to bind to HLA-A(*)0201 and are not recognized by T lymphocytes. As processing of prostate stem cell antigen by signal peptidase occurs immediately after co-translational insertion, the epitope must be processed from polypeptides that have never reached the ER. The processing of this epitope depends on the proteasome and the transporter associated with antigen processing and shows a novel pathway of class I processing that relies on the failure of ER-targeted proteins to reach their target compartment. PMID- 17853905 TI - Microbial oceanography: paradigms, processes and promise. AB - Life on Earth most likely originated as microorganisms in the sea. Over the past approximately 3.5 billion years, microorganisms have shaped and defined Earth's biosphere and have created conditions that have allowed the evolution of macroorganisms and complex biological communities, including human societies. Recent advances in technology have highlighted the vast and previously unknown genetic information that is contained in extant marine microorganisms, from new protein families to novel metabolic processes. Now there is a unique opportunity, using recent advances in molecular ecology, metagenomics, remote sensing of microorganisms and ecological modelling, to achieve a comprehensive understanding of marine microorganisms and their susceptibility to environmental variability and climate change. Contemporary microbial oceanography is truly a sea of opportunity and excitement. PMID- 17853906 TI - Microbial structuring of marine ecosystems. AB - Despite the impressive advances that have been made in assessing the diversity of marine microorganisms, the mechanisms that underlie the participation of microorganisms in marine food webs and biogeochemical cycles are poorly understood. Here, we stress the need to examine the biochemical interactions of microorganisms with ocean systems at the nanometre to millimetre scale--a scale that is relevant to microbial activities. The local impact of microorganisms on biogeochemical cycles must then be scaled up to make useful predictions of how marine ecosystems in the whole ocean might respond to global change. This approach to microbial oceanography is not only helpful, but is in fact indispensable. PMID- 17853907 TI - Marine viruses--major players in the global ecosystem. AB - Viruses are by far the most abundant 'lifeforms' in the oceans and are the reservoir of most of the genetic diversity in the sea. The estimated 10(30) viruses in the ocean, if stretched end to end, would span farther than the nearest 60 galaxies. Every second, approximately 10(23) viral infections occur in the ocean. These infections are a major source of mortality, and cause disease in a range of organisms, from shrimp to whales. As a result, viruses influence the composition of marine communities and are a major force behind biogeochemical cycles. Each infection has the potential to introduce new genetic information into an organism or progeny virus, thereby driving the evolution of both host and viral assemblages. Probing this vast reservoir of genetic and biological diversity continues to yield exciting discoveries. PMID- 17853908 TI - Mix and match: how climate selects phytoplankton. AB - Climate strongly influences the distribution and diversity of animals and plants, but its affect on microbial communities is poorly understood. By using resource competition theory, fundamental physical principles and the fossil record we review how climate selects marine eukaryotic phytoplankton taxa. We suggest that climate determines the equator-to-pole and continent-to-land thermal gradients that provide energy for the wind-driven turbulent mixing in the upper ocean. This mixing, in turn, controls the nutrient fluxes that determine cell size and taxa level distributions. Understanding this chain of linked processes will allow informed predictions to be made about how phytoplankton communities will change in the future. PMID- 17853909 TI - The importance of culturing bacterioplankton in the 'omics' age. AB - Progress in the culturing of microorganisms that are important to ocean ecology has recently accelerated, and technology has been a factor in these advances. However, rather than a single technological breakthrough, a combination of methods now enable microbiologists to screen large numbers of cultures and manipulate cells that are growing at the low biomass densities that are characteristic of those found in seawater. The value of ribosomal RNA databases has been reaffirmed, as they provide nucleic-acid probes for screening to identify important new species in culture. The new cultivation approaches have focused on specific targets that ecological studies suggest are significant for geochemical transformations, such as SAR11. Here, we review how to cultivate marine oligotrophs and why it is worth the effort. PMID- 17853910 TI - Introduction to genetic association studies. PMID- 17853915 TI - Resident retreat for future academicians. PMID- 17853916 TI - Recessive dystrophic epidermolysis bullosa-associated squamous-cell carcinoma: an enigmatic entity with complex pathogenesis. AB - Expression of either collagen VII or the noncollagenous (NC1) fragment derived from it has been suggested to be indispensable for the development of squamous cell carcinomas (SCCs) in patients affected by recessive dystrophic epidermolysis bullosa (RDEB). This view is challenged here by the observation that SCCs do develop in RDEB patients lacking expression of collagen VII altogether. The aggressive behavior of RDEB-associated SCCs remains unexplained. PMID- 17853917 TI - Genital and nongenital nonmelanoma skin cancer: more epidemiological studies are needed. AB - Although black men in the United States have a lower mortality of nongenital nonmelanoma skin cancer (NMSC) than white men, they have a higher mortality of genital NMSC than white men. Mortality of NMSC has declined over time. Ethnicity specific incidence and survival analyses of NMSC can be used to determine to what degree earlier detection and/or more efficient therapies have contributed to these observations. PMID- 17853918 TI - Why are quality of life instruments not recognized as reference measures in therapeutic trials of chronic skin disorders? AB - Patient-reported outcomes, especially heath-related quality of life (HRQOL) outcomes, are particularly relevant for chronic skin disorders (CSDs), because lesion scores such as PASI are less meaningful in making therapeutic decisions. Patient perception of the disease impact, such as HRQOL, should be the main outcome measure in therapeutic trials for CSDs, especially for expensive biotherapies. To be credible as reference measures, dermatology-specific instruments of HRQOL must generate similar scores in different countries and different cultures. Because none of the currently used instruments--e.g., the Dermatology Life Questionnaire Index (DLQI) and Skindex--fulfills this requirement, it is important to generate new instruments or adapt existing ones. PMID- 17853920 TI - Comparison of the E3 and L3 regions for arming oncolytic adenoviruses to achieve a high level of tumor-specific transgene expression. AB - Arming oncolytic adenoviral vectors with anticancer transgenes that can be expressed in a tumor-selective manner may enable the engineering of vectors with increased potency, while retaining their safety profile. Armed oncolytic adenoviral vectors were constructed in which transgene expression has been linked via modified splice acceptor sequences that did not necessitate the deletion of any part of the adenoviral genome. Several oncolytic adenoviral vectors were compared in which the transgene was inserted in place of either the E3 or the L3 region. While all vectors had similar viral growth and cytotoxicity characteristics, the highest level of transgene expression was observed from a vector in which the transgene had been inserted downstream of the L3 23K protease gene, the Ad-23K-GM vector. Notably, no transgene expression occurred with this vector in the absence of DNA replication either in vitro or in vivo. In contrast, viruses in which the transgene was inserted into E3 locations exhibited a low level of transgene expression even in the absence of DNA replication. In summary, by utilizing the L3 region for arming oncolytic viruses, higher levels of tumor specific transgene expression can be obtained without the need to delete any parts of the viral genome. PMID- 17853922 TI - An oncolytic mutant of herpes simplex virus type-1 in which replication is governed by a promoter/enhancer of human papillomavirus type-16. AB - Although herpes simplex virus type-1 (HSV-1) can be used as an oncolytic virus it has the undesirable side effect of neurotoxicity. To create a virus with improved specificity for oral cancer we used a fragment of human papillomavirus type-16, which is frequently found in oral and cervical cancers, but not elsewhere. The upstream regulatory region, URR16, was shown to have a high level of transcriptional activity in three of four oral cancer cell lines but low activity in three cell lines derived from brain cancers. URR16 was therefore placed in HSV 1, replacing the promoter of the essential gene ICP4, and the resulting virus was named HSPV-1. When cells were infected with HSPV-1, ICP4 was expressed at levels that were not associated with the level of activity of URR16. The virus replicated in each type of cell to a final titer that showed a correlation with the level of expression of ICP4, but with no correlation to either the tumor of origin or the presence of HPV sequences in the cells. To find if some function of HSV-1 was affecting the activity of URR16, oral cancer cells were transfected with a URR-reporter construct and were then infected with virus. This induced transcription, which was attributed to immediate-early viral genes other than ICP4. A promoter/enhancer from a papillomavirus therefore has the potential to regulate the functions of an oncolytic strain of HSV-1, and is affected by functions of both the host cell and of HSV-1 itself. PMID- 17853923 TI - DcR2 (TRAIL-R4) siRNA and adenovirus delivery of TRAIL (Ad5hTRAIL) break down in vitro tumorigenic potential of prostate carcinoma cells. AB - High levels of decoy receptor 2 (DcR2; TRAIL-R4) expression are correlated with TRAIL resistance in prostate cancer cells. In addition, upregulation of TRAIL death receptor (DR4 and DR5) expression, either by ionizing radiation or chemotherapy, can sensitize cancer cells to TRAIL. Considering more than half of human cancers are TRAIL resistant, modulation of surface TRAIL receptor expression appears to be an attractive treatment modality to counteract TRAIL resistance. In this study, three siRNA duplexes targeting DcR2 receptor were tested. Ad5hTRAIL infections were performed to overexpress human full-length TRAIL to induce cell death, and the in vitro tumorigenic potential of prostate cancer cells was assessed using colony-forming assays on soft agar. The DU145 and LNCaP prostate cancer cell lines, which express high levels of DcR2, were resistant to Ad5hTRAIL-induced death. Downregulation of surface DcR2 expression by siRNA sensitized these prostate cancer cell lines to Ad5hTRAIL. In addition, DcR2 siRNA-mediated knockdown of DcR2, followed by Ad5hTRAIL infection, dramatically reduced the in vitro tumorigenic potential of prostate cancer cells. Collectively, our results suggest the potential for combining receptor-specific siRNA with TRAIL in the treatment of certain cancers. PMID- 17853921 TI - Enhancement of intratumoral cyclophosphamide pharmacokinetics and antitumor activity in a P450 2B11-based cancer gene therapy model. AB - The therapeutic utility of cytochrome P450-based enzyme prodrug therapy is well established by preclinical studies and in initial clinical trials. The underlying premise of this gene therapy is that intratumoral P450 expression leads to in situ activation of anticancer P450 prodrugs, such as cyclophosphamide (CPA), with intratumoral accumulation of its activated 4-OH metabolite. In mice bearing 9L gliosarcomas expressing the CPA 4-hydroxylase P450 2B6, enhanced tumor apoptosis was observed 48 h after CPA treatment; however, intratumoral 4-OH-CPA levels were indistinguishable from those of P450-deficient tumors, indicating that the bulk of activated CPA is derived from hepatic metabolism. In contrast, in 9L tumors expressing P450 2B11, a low K(m) CPA 4-hydroxylase, intratumoral 4-OH-CPA levels were higher than in blood, liver and P450-deficient tumors. Intratumoral 4-OH-CPA increased dose-dependently, without saturation at 140 mg kg(-1) CPA, suggesting restricted tumor cell permeation of the parent drug. To circumvent this problem, CPA was administered by direct intratumoral injection, which increased the maximum concentration and area under the curve of drug concentration x time (AUC) of intratumoral 4-OH-CPA by 1.8- and 2.7-fold, respectively. An overall 3.9-fold increase in intratumoral 4-OH-CPA AUC, and in antitumor activity, was obtained when CPA release to systemic circulation was delayed using the slow-release polymer poloxamer 407 as vehicle for intratumoral CPA delivery. These findings highlight the advantage of gene therapy strategies that combine low K(m) P450 prodrug activation enzymes with slow, localized release of P450 prodrug substrates. PMID- 17853924 TI - An archaeal histone-like protein mediates efficient p53 gene transfer and facilitates its anti-cancer effect in vitro and in vivo. AB - The improvement of the transfection efficiency of the non-viral-based gene delivery systems is a key issue for the application in gene therapy. We have previously described an archaeal histone-like protein-based (HPhA) gene delivery system and showed that HPhA formed stable non-covalent complexes with nucleic acids and improved their delivery by using beta-galactosidase as a reporter gene. In this study, the wild-type p53 gene was transfected into the cancer cells using the HPhA as a vector, and the expression level and the activity of p53 gene were evaluated both in vitro and in vivo. Gene expression was determined by real-time reverse transcriptase-PCR and western blotting analysis. The cellular growth inhibition and apoptosis of HPhA-mediated p53 transfection were assessed by XTT (sodium 3'-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis(4-methoxy-6 nitro)benzene sulfonic acid hydrate) assay and annexin V-FITC (fluorescein isothiocyanate) staining, respectively. Further more, transfection of HPhA/p53 into CNE (nasopharyngeal carcinoma cell line)-xenografted nude mice was performed and tumor growth was measured. The present study demonstrates that HPhA enhances the efficiency of p53 gene transfer and antitumor activity compared with the widely used Lipofectamine. These results demonstrate that HPhA enhances the in vitro and in vivo efficiency of p53 gene transfer and suggest that it may be served as a promising tool for gene delivery and gene therapy. PMID- 17853925 TI - Sudden cardiac death in the young: don't forget abnormal coronary arteries! PMID- 17853926 TI - Blue-collar workplaces: a setting for reducing heart health inequalities in New Zealand? AB - AIM: To review the evidence for the effectiveness of workplaces as settings for cardiovascular health promotion and reduction of heart health inequalities in New Zealand. METHODS: Literature review and structured appraisal of 154 articles meeting inclusion criteria, of which one review and three trials addressed cardiovascular interventions specifically, and four systematic reviews addressed the effectiveness of workplace health promotion programmes generally. RESULTS: The reviewed studies showed that workplaces have good potential as settings for health promotion. We found mixed but largely supportive evidence that workplace interventions can lead to improvements in health outcomes, workplace environments, lifestyles, and productivity. Workplace programmes that ranked highest in both clinical and cost-effectiveness targeted industries employing large numbers of blue-collar workers, tackled multiple risk factors, intervened at both individual and environmental levels and incorporated occupational safety components. Such programmes appear to offer a substantial return on investment for employers in other countries, but local evidence is lacking. CONCLUSIONS: Employers and workers in blue-collar industries should be encouraged to participate in comprehensive heart health promotion programmes as a strategy for reducing existing socioeconomic and ethnic disparities in health. However, high quality evidence of improved employee health and productivity is needed from well designed New Zealand-based research to ensure that these programmes are optimally configured for effectiveness and attractive to employers and employees alike. PMID- 17853927 TI - Accuracy of the Wells Rule in diagnosing deep vein thrombosis in primary health care. AB - AIM: A clinical decision rule to aid in the diagnosis of deep vein thrombosis (DVT) was derived by Wells and has been validated in several secondary care settings. It is now used to reduce unnecessary radiological examinations. The aim of this study was to assess the accuracy of the Wells Rule in New Zealand primary health care. METHOD: Validation study of the Wells clinical decision rule for DVT in primary health care, using ultrasound as the comparator. Participants included patients with symptoms of DVT from 410 general practitioners in Auckland between 1 October 2004 and 30 September 2005. Sensitivity, specificity, and likelihood ratios were calculated. RESULTS: 432 patients were assessed over 12 months, of whom 327 were eligible to participate. Mean age was 65.5 years (SD 16.1) and 203 (62%) were women. DVT was confirmed in 12% (39/327). Sensitivity was 82% (95% confidence interval [CI]: 67.3-91.0) and specificity 22.5% (CI: 18.1-27.7). Likelihood ratio for a positive test was 1.06 (CI: 0.90-1.24) and for a negative test 0.80 (CI: 0.39-1.61). CONCLUSION: The Wells Rule used alone had only moderate sensitivity and poor specificity and likelihood ratios, so has limited use in the diagnosis of DVT in primary care. PMID- 17853928 TI - Is it time to stop treating dyslipidaemia with fibrates? AB - AIM: To determine whether evidence from randomised clinical trials supports the use of fibrates to reduce non-fatal and fatal cardiovascular events in patients with dyslipidaemia. METHOD: Review of randomised clinical trials of fibrates that assess clinical outcomes. RESULT: In clinical trials which have which have included over 40,000 patients there was no difference in all cause mortality for patients randomised to a fibrate compared to placebo. Treatment with a fibrate was associated with a small reduction in the risk of non-fatal cardiovascular events. DISCUSSION: Current evidence does not support the use of fibrates to reduce cardiovascular mortality. Other proven strategies including statins, aspirin, angiotension converting enzyme (ACE) inhibitors, good blood pressure control, and lifestyle interventions should be used to reduce cardiovascular risk. PMID- 17853929 TI - Trading PREDICTions. PMID- 17853930 TI - Reducing the lifetime cardiovascular risk of New Zealanders. PMID- 17853931 TI - A 40-year-old woman with breathlessness. PMID- 17853932 TI - Medical image. Radiologic evolution of pulmonary thromboembolism with infarct. PMID- 17853933 TI - The impact of New Zealand CVD risk chart adjustments for family history and ethnicity on eligibility for treatment (PREDICT CVD-5). AB - AIMS: Current New Zealand cardiovascular (CVD) risk management guidelines advocate targeting treatment to patients with a high 5-year CVD risk assessed using a calculator derived from the Framingham Heart Study. For some high-risk population subgroups, a 5% upward adjustment to their calculated 5-year CVD risk is recommended. We estimated the impact of these adjustments on eligibility for treatment in a primary care setting. METHODS: Between 2002 and 2006, 23,709 patients visiting their primary care provider in Auckland, New Zealand had CVD risk assessments as part of an opportunistic screening programme using PREDICT, a web-based clinical decision support system. We calculated their baseline CVD risk with and without the 5% upward adjustment for family history of premature ischaemic CVD or for being of Maori, Pacific or Indian subcontinent ethnicity. RESULTS: A baseline CVD risk could be calculated for 23,693 (99.9%) patients of whom 90% were between ages 35 and 74 years. Unadjusted risk scores classified the majority (70%) below the 10% 5-year risk threshold for specific individualised treatment. A further 11% were between 10 to 15% risk (recommended to receive individualised lifestyle counselling in general practice) and 19% had a greater than 15% risk ( recommended for drug treatment and referral to a dietician in addition to individualised lifestyle counselling). Over a quarter of patients were recorded as having a premature family history of CVD; 21% were Maori, Pacific, or Indian subcontinent and thus met the criteria for a single 5% upward adjustment. This increased the number of people eligible for drug treatment, intensive lifestyle management, and dietician referral by approximately 20% and individualised lifestyle assessment and counselling by 50%. CONCLUSIONS: The upward adjustments to the calculated CVD risk recommended by the New Zealand CVD risk management guidelines has the potential to substantially increase resource requirements for CVD preventive services in primary care. Moreover the true impact is likely to be underestimated given other adjustment factors related to diabetes risk that were not available in this dataset. Given the impact of these relatively small changes to the CVD risk calculator, locally developed and validated risk equations are urgently needed. PMID- 17853934 TI - Survival over 5 years in the initial hospital survivors with acute coronary syndrome: a comparison between a community hospital and a tertiary hospital in New Zealand. AB - AIMS: To compare the outcome of hospital survivors with acute coronary syndrome (ACS) discharged from a community hospital (Invercargill hospital) versus from a tertiary teaching (Dunedin) hospital followed for up to 5 years. METHODS: All ACS survivors discharged from Dunedin and Invercargill coronary care units between the years 2000-2002 were included. We previously found higher 1-year mortality for Invercargill patients but the explanation was unclear. RESULTS: Of the 844 patients admitted to Dunedin and 299 admitted to Invercargill hospital, 1057 survived the index ACS episode and formed the cohort for the current study. At 2 years, the mortality of these initial survivors was 8.5% higher for Invercargill patients (18.4% vs 9.9%, p<0.001). Over up to 5 years of follow-up, comparing Invercargill patients to Dunedin patients, the unadjusted hazard ratio for mortality was 1.26 (95%CI: 0.90-1.75). After adjusting to the hospital discharge GRACE score (119+/-40 for Dunedin patients and 130+/-40 for Invercargill patients, p=0.001), this dropped to 1.12 (95%CI: 0.80-1.57). After further adjusting to the discharge medications aspirin (97% vs 98%) and ACE-inhibitors (53% vs 49%), this was 1.14 (95%CI 0.81-1.59). After further adjusting to the use of beta-blockers (78% vs 71%), this was 1.07 (95%CI: 0.76-1.50). After final adjustment for the use of statins (65% vs 42%), this was 0.96 (95%CI: 0.68-1.36). CONCLUSION: Patients discharged from Invercargill hospital fare worse over the first 2-years and tended to fare worse over the first 5-years. This was due both to their higher baseline risk at discharge and the under-use of statins. Of note, PHARMAC rules for statins only changed around the end of the study period allowing more liberal use of statins. PMID- 17853935 TI - Issues in the assessment of cardiovascular risk in selected general practices in Canterbury, New Zealand. AB - AIMS: The aim was to audit patient records at selected general practices in Canterbury, New Zealand to assess the potential: (a) to improve identification and management of people with risk factors for cardiovascular disease (CVD); and (b) to develop a geographically distinct community database of CVD risk factor prevalence that could be used to plan public health programmes to improve cardiovascular health. METHODS: Patient records were audited in three general practices in a Canterbury rural town and information on cardiovascular risk factors recommended for the screening and management of CVD by the New Zealand Guidelines Group was extracted and entered into an electronic database. The data was analysed to assess the extent of recording of information on recommended risk factors. RESULTS: Most patient records contained information on smoking, blood pressure and lipid profiles. Low levels of information recording were found for physical activity, body mass index (BMI), and family history. There were statistically significant differences between general practices in the type and coverage of information recorded, even for patients with diagnosed cardiovascular disease. Because of deficiencies in information, it was not possible to calculate CVD risk using the guidelines for 43% of patients. Some practices remain reliant on paper records which make it extremely difficult to undertake a systematic programme of screening and management of CVD risk factors. CONCLUSIONS: Before it is practical to undertake a systematic screening programme for CVD risk factors in primary care, it is necessary to reduce reliance on paper records and to fully implement computerised patient management systems that allow for information storage and retrieval. In addition, it is essential to improve the systematic collection of key information in primary care that is used to assess risk of CVD. PMID- 17853936 TI - Regarding the 'Five-year experience of corneal scrapes at Wellington Eye Department, New Zealand' article. PMID- 17853937 TI - Campylobacter infection and chicken: an update on New Zealand's largest 'common source outbreak'. PMID- 17853938 TI - Regarding the 'Phytophotodermatitis caused by contact with a fig tree (Ficus carica)' case report, and response. PMID- 17853939 TI - Health-related quality of life after radical cystectomy for bladder cancer in elderly patients with an ileal conduit, ureterocutaneostomy, or orthotopic urinary reservoir: a comparative questionnaire survey. AB - To compare the health-related quality of life of elderly patients after radical cystectomy for bladder cancer in urinary diversion groups: ileal conduit, ureterocutaneostomy, or orthotopic urinary reservoir. The 109 participating elderly patients aged 75 or older completed self-reporting questionnaires: the QLQ-C30, and on satisfaction with urinary diversion methods. Fifty-six patients had undergone constructions for ileal conduit diversion, 31 for ureterocutaneostomy, and 22 for orthotopic urinary reservoir (OUR). The median follow-up period for each group was 4.0 years (range 0.3-11.2), 4.5 years (range 0.3-18.0), and 3.3 years (range 0.3-6.7), respectively. Regardless of the type of urinary diversion, the majority of patients reported having good overall quality of life, although with some problem of pain. No significant differences among urinary diversion subgroups were found in any quality of life area in the QLQ-C30 questionnaire. More patients in the OUR sub-group felt disappointment than those in the ileal conduit or cutaneostomy sub-groups. However, a questionnaire which asked which diversion method would be preferable showed a trend that more patients in the OUR subgroup would have chosen the same one. Health-related quality of life appeared relatively good in these 3 groups. Patient demands and expectations may be so different from the results that the details of each urinary diversion method should be explained thoroughly. OUR construction could be a candidate even for elderly patients. PMID- 17853940 TI - Immune suppression or enhancement by CD137 T cell costimulation during acute viral infection is time dependent. AB - CD137 is expressed on activated T cells and ligands to this costimulatory molecule have clinical potential for amplifying CD8 T cell immunity to tumors and viruses, while suppressing CD4 autoimmune T cell responses. To understand the basis for this dichotomy in T cell function, CD4 and CD8 antiviral immunity was measured in lymphocytic choriomeningitis virus (LCMV) Armstrong- or A/PR8/34 influenza-infected mice injected with anti-CD137 mAbs. We found that the timing of administration of anti-CD137 mAbs profoundly altered the nature of the antiviral immune response during acute infection. Antiviral immunity progressed normally for the first 72 hours when the mAb was administered early in infection before undergoing complete collapse by day 8 postinfection. Anti-CD137-injected LCMV-infected mice became tolerant to, and persistently infected with, LCMV Armstrong. Elevated levels of IL-10 early in the response was key to the loss of CD4(+) T cells, whereas CD8(+) T cell deletion was dependent on a prolonged TNF alpha response, IL-10, and upregulation of Fas. Blocking IL-10 function rescued CD4 antiviral immunity but not CD8(+) T cell deletion. Anti-CD137 treatment given beyond 72 hours after infection significantly enhanced antiviral immunity. Mice treated with anti-CD137 mAb 1 day before infection with A/PR8/34 virus experienced 80% mortality compared with 40% mortality of controls. When treatment was delayed until day 1 postinfection, 100% of the infected mice survived. These data show that anti-CD137 mAbs can induce T cell activation-induced cell death or enhance antiviral immunity depending on the timing of treatment, which may be important for vaccine development. PMID- 17853941 TI - Targeted gene deletion in Candida parapsilosis demonstrates the role of secreted lipase in virulence. AB - Candida parapsilosis is a major cause of human disease, yet little is known about the pathogen's virulence. We have developed an efficient gene deletion system for C. parapsilosis based on the repeated use of the dominant nourseothricin resistance marker (caSAT1) and its subsequent deletion by FLP-mediated, site specific recombination. Using this technique, we deleted the lipase locus in the C. parapsilosis genome consisting of adjacent genes CpLIP1 and CpLIP2. Additionally we reconstructed the CpLIP2 gene, which restored lipase activity. Lipolytic activity was absent in the null mutants, whereas the WT, heterozygous, and reconstructed mutants showed similar lipase production. Biofilm formation was inhibited with lipase-negative mutants and their growth was significantly reduced in lipid-rich media. The knockout mutants were more efficiently ingested and killed by J774.16 and RAW 264.7 macrophage-like cells. Additionally, the lipase negative mutants were significantly less virulent in infection models that involve inoculation of reconstituted human oral epithelium or murine intraperitoneal challenge. These studies represent what we believe to be the first targeted disruption of a gene in C. parapsilosis and show that C. parapsilosis-secreted lipase is involved in disease pathogenesis. This efficient system for targeted gene deletion holds great promise for rapidly enhancing our knowledge of the biology and virulence of this increasingly common invasive fungal pathogen. PMID- 17853942 TI - Synergistic airway gland mucus secretion in response to vasoactive intestinal peptide and carbachol is lost in cystic fibrosis. AB - Cystic fibrosis (CF) is caused by dysfunction of the CF transmembrane conductance regulator (CFTR), an anion channel whose dysfunction leads to chronic bacterial and fungal airway infections via a pathophysiological cascade that is incompletely understood. Airway glands, which produce most airway mucus, do so in response to both acetylcholine (ACh) and vasoactive intestinal peptide (VIP). CF glands fail to secrete mucus in response to VIP, but do so in response to ACh. Because vagal cholinergic pathways still elicit strong gland mucus secretion in CF subjects, it is unclear whether VIP-stimulated, CFTR-dependent gland secretion participates in innate defense. It was recently hypothesized that airway intrinsic neurons, which express abundant VIP and ACh, are normally active and stimulate low-level gland mucus secretion that is a component of innate mucosal defenses. Here we show that low levels of VIP and ACh produced significant mucus secretion in human glands via strong synergistic interactions; synergy was lost in glands of CF patients. VIP/ACh synergy also existed in pig glands, where it was CFTR dependent, mediated by both Cl(-) and HCO(3) (-), and clotrimazole sensitive. Loss of "housekeeping" gland mucus secretion in CF, in combination with demonstrated defects in surface epithelia, may play a role in the vulnerability of CF airways to bacterial infections. PMID- 17853943 TI - Proatherogenic immune responses are regulated by the PD-1/PD-L pathway in mice. AB - T lymphocyte responses promote proatherogenic inflammatory events, which are influenced by costimulatory molecules of the B7 family. Effects of negative regulatory members of the B7 family on atherosclerosis have not been described. Programmed death-ligand 1 (PD-L1) and PD-L2 are B7 family members expressed on several cell types, which inhibit T cell activation via binding to programmed death-1 (PD-1) on T cells. In order to test whether the PD-1/PD-L pathway regulates proatherogenic T cell responses, we compared atherosclerotic lesion burden and phenotype in hypercholesterolemic PD-L1/2(-/-)LDLR(-/-) mice and LDLR( /-) controls. PD-L1/2 deficiency led to significantly increased atherosclerotic burden throughout the aorta and increased numbers of lesional CD4(+) and CD8(+) T cells. Compared with controls, PD-L1/2(-/-)LDLR(-/-) mice had iliac lymphadenopathy and increased numbers of activated CD4(+) T cells. Serum levels of TNF-alpha were higher in PD-L1/2(-/-)LDLR(-/-) mice than in controls. PD-L1/2 deficient APCs were more effective than control APCs in activating CD4(+) T cells in vitro, with or without cholesterol loading. Freshly isolated APCs from hypercholesterolemic PD-L1/2(-/-)LDLR(-/-) mice stimulated greater T cell responses than did APCs from hypercholesterolemic controls. Our findings indicate that the PD-1/PD-L pathway has an important role in downregulating proatherogenic T cell response and atherosclerosis by limiting APC-dependent T cell activation. PMID- 17853944 TI - Redox modifier genes in amyotrophic lateral sclerosis in mice. AB - Amyotrophic lateral sclerosis (ALS), one of the most common adult-onset neurodegenerative diseases, has no known cure. Enhanced redox stress and inflammation have been associated with the pathoprogression of ALS through a poorly defined mechanism. Here we determined that dysregulated redox stress in ALS mice caused by NADPH oxidases Nox1 and Nox2 significantly influenced the progression of motor neuron disease caused by mutant SOD1(G93A) expression. Deletion of either Nox gene significantly slowed disease progression and improved survival. However, 50% survival rates were enhanced significantly more by Nox2 deletion than by Nox1 deletion. Interestingly, female ALS mice containing only 1 active X-linked Nox1 or Nox2 gene also had significantly delayed disease onset, but showed normal disease progression rates. Nox activity in spinal cords from Nox2 heterozygous female ALS mice was approximately 50% that of WT female ALS mice, suggesting that random X-inactivation was not influenced by Nox2 gene deletion. Hence, chimerism with respect to Nox-expressing cells in the spinal cord significantly delayed onset of motor neuron disease in ALS. These studies define what we believe to be new modifier gene targets for treatment of ALS. PMID- 17853945 TI - TLR4 activation mediates kidney ischemia/reperfusion injury. AB - Ischemia/reperfusion injury (IRI) may activate innate immunity through the engagement of TLRs by endogenous ligands. TLR4 expressed within the kidney is a potential mediator of innate activation and inflammation. Using a mouse model of kidney IRI, we demonstrated a significant increase in TLR4 expression by tubular epithelial cells (TECs) and infiltrating leukocytes within the kidney following ischemia. TLR4 signaling through the MyD88-dependent pathway was required for the full development of kidney IRI, as both TLR4(-/-) and MyD88(-/-) mice were protected against kidney dysfunction, tubular damage, neutrophil and macrophage accumulation, and expression of proinflammatory cytokines and chemokines. In vitro, WT kidney TECs produced proinflammatory cytokines and chemokines and underwent apoptosis after ischemia. These effects were attenuated in TLR4(-/-) and MyD88(-/-) TECs. In addition, we demonstrated upregulation of the endogenous ligands high-mobility group box 1 (HMGB1), hyaluronan, and biglycan, providing circumstantial evidence that one or more of these ligands may be the source of TLR4 activation. To determine the relative contribution of TLR4 expression by parenchymal cells or leukocytes to kidney damage during IRI, we generated chimeric mice. TLR4(-/-) mice engrafted with WT hematopoietic cells had significantly lower serum creatinine and less tubular damage than WT mice reconstituted with TLR4(-/-) BM, suggesting that TLR4 signaling in intrinsic kidney cells plays the dominant role in mediating kidney damage. PMID- 17853946 TI - TREM-1--expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases. AB - Triggering receptor expressed on myeloid cells-1 (TREM-1) potently amplifies acute inflammatory responses by enhancing degranulation and secretion of proinflammatory mediators. Here we demonstrate that TREM-1 is also crucially involved in chronic inflammatory bowel diseases (IBD). Myeloid cells of the normal intestine generally lack TREM-1 expression. In experimental mouse models of colitis and in patients with IBD, however, TREM-1 expression in the intestine was upregulated and correlated with disease activity. TREM-1 significantly enhanced the secretion of relevant proinflammatory mediators in intestinal macrophages from IBD patients. Blocking TREM-1 by the administration of an antagonistic peptide substantially attenuated clinical course and histopathological alterations in experimental mouse models of colitis. This effect was also seen when the antagonistic peptide was administered only after the first appearance of clinical signs of colitis. Hence, TREM-1-mediated amplification of inflammation contributes not only to the exacerbation of acute inflammatory disorders but also to the perpetuation of chronic inflammatory disorders. Furthermore, interfering with TREM-1 engagement leads to the simultaneous reduction of production and secretion of a variety of pro inflammatory mediators such as TNF, IL-6, IL-8 (CXCL8), MCP-1 (CCL2), and IL 1beta. Therefore, TREM-1 may also represent an attractive target for the treatment of chronic inflammatory disorders. PMID- 17853948 TI - Management of anticoagulants and antiplatelet agents in elective endoscopy: weighing the risks and benefits. PMID- 17853947 TI - Calpain activation impairs neuromuscular transmission in a mouse model of the slow-channel myasthenic syndrome. AB - The slow-channel myasthenic syndrome (SCS) is a hereditary disorder of the acetylcholine receptor (AChR) of the neuromuscular junction (NMJ) that leads to prolonged AChR channel opening, Ca(2+) overload, and degeneration of the NMJ. We used an SCS transgenic mouse model to investigate the role of the calcium activated protease calpain in the pathogenesis of synaptic dysfunction in SCS. Cleavage of a fluorogenic calpain substrate was increased at the NMJ of dissociated muscle fibers. Inhibition of calpain using a calpastatin (CS) transgene improved strength and neuromuscular transmission. CS caused a 2-fold increase in the frequency of miniature endplate currents (MEPCs) and an increase in NMJ size, but MEPC amplitudes remained reduced. Persistent degeneration of the NMJ was associated with localized activation of the non-calpain protease caspase 3. This study suggests that calpain may act presynaptically to impair NMJ function in SCS but further reveals a role for other cysteine proteases whose inhibition may be of additional therapeutic benefit in SCS and other excitotoxic disorders. PMID- 17853949 TI - Long-term follow-up of individuals with celiac disease: an evaluation of current practice guidelines. AB - INTRODUCTION: Celiac disease can be treated by following a strict gluten-free diet for life. If properly followed, the diet resolves symptoms and nutritional deficiencies. It is generally recommended that individuals with celiac disease have careful long-term follow-up. However, it is not clear which elements of disease status evaluation, laboratory investigations and self-management support should be included in follow-up. OBJECTIVES: To examine the current practice guidelines and recommendations regarding follow-up of individuals with celiac disease. METHODS: Guidelines issued by gastroenterological societies and associations, and recommendations by experts were retrieved using Medline and other Internet search engines. RESULTS: Practice guidelines were available from the American Gastroenterological Association; the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition; the National Institutes of Health Consensus Development Conference 2004; the World Gastroenterology Organization; the British Society for Gastroenterology and the United Kingdom based Primary Care Society for Gastroenterology. Most guidelines recommended a scheduled annual review and regular measurements of body mass index. The British Society for Gastroenterology recommended dietary review only at times of stress, while others recommended dietary review with a nutritionist. All associations recommended serial tissue transglutaminase antibody testing. The American Gastroenterological Association and the Primary Care Society for Gastroenterology recommended annual hemoglobin, ferritin and folate checks. One guideline recommended annual hemoglobin, electrolyte, calcium, albumin, ferritin, folate, fat-soluble vitamin, liver function test, parathyroid hormone and bone density measurements (approximately $400 per patient). CONCLUSIONS: The current practice guidelines regarding the follow-up of patients with celiac disease varied greatly in their recommendations and many were not evidence-based. Prospective studies are required to develop rational, cost-effective and risk-stratified guidelines for long-term follow-up of these patients. PMID- 17853950 TI - Retrospective review of pediatric and adult autoimmune hepatitis in two quaternary care centres in British Columbia: increased prevalence seen in British Columbia's First Nations community. AB - BACKGROUND: It has been previously reported that British Columbia's (BC's) First Nations (Aboriginal) community has an increased risk of autoimmune diseases, including rheumatological conditions (rheumatoid arthritis, systemic lupus) and primary biliary cirrhosis. The researchers hypothesized that this community may also be at increased risk for autoimmune hepatitis (AIH). METHODS: Independent, retrospective reviews of the databases of two separate tertiary/quaternary British Columbia university-affiliated health care institutions, the Adult Liver Transplant Program of the BC Transplant Society and the Division of Pediatric Gastroenterology, BC Children's Hospital (Vancouver, BC), were performed. All patients referred with a diagnosis of probable or definite AIH who identified themselves as being of First Nations descent from 1988 to 2004 were reviewed. The liver transplant database records all adult patients in the province referred for transplant assessment. The pediatric database records all children referred to the BC Children's Hospital. RESULTS: A total of 68 adult patients with a definite or probable diagnosis of AIH were referred to the liver transplant program. Twelve patients (17.6%) were Aboriginal, 11 of which were female. Similarly, a total of 30 children with probable or definite AIH were identified from the pediatric database. Six of these cases (20%) were identified in Aboriginal children. CONCLUSIONS: The findings suggest an increased prevalence of AIH among BC's First Nations community. A disproportionate First Nations representation was found on independent review of two databases. Future studies are needed to determine the true prevalence of AIH in this community, and to uncover the genetic predisposition and the environmental triggers explaining this phenomenon. PMID- 17853951 TI - Association of apolipoprotein A1-C3 gene cluster polymorphisms with gallstone disease. AB - INTRODUCTION: Genetic polymorphisms in apolipoprotein genes may be associated with alteration in lipid profile and susceptibility to gallstone disease. AIM: To determine the association between apolipoprotein A1 (APOA1) -75 guanine [G] to adenine [A] and +83/84 M2(+/-), MspI) and apolipoprotein C3 (APOC3) (SstI) polymorphisms with gallstone disease. METHODS: MspI polymorphisms of the APOA1 gene and SstI polymorphisms of APOC3 were analyzed in DNA samples of 214 gallstone patients and 322 age- and sex-matched healthy controls. All statistical analyses were performed using SPSS version 11.5 (SPSS, USA) and Arlequin version 2.0 (Arlequin, Switzerland). RESULTS: The APOA1 -75 G/A polymorphism was significantly associated with gallstone disease. Patients with the GG genotype (P=0.015) and G allele carriers (P=0.004) had a significantly higher risk of gallstone disease (1.087-fold and 1.561-fold, respectively), whereas patients with AA genotypes (P=0.011) and A allele carriers (P=0.004) were protected (OR 0.230 and 0.641, respectively) against gallstone disease. APOA1 +83 M2(+/-) and APOC3 SstI polymorphisms were not associated with gallstone disease. Case-control analysis of haplotypes showed a significant association in males only. G-M2(+)-S1 conferred risk for gallstone disease (P=0.036; OR 1.593, 95% CI 1.029 to 2.464), while A-M2(+)-S1 was protective (P=0.002; OR 0.370, 95% CI 0.197 to 0.695) against gallstone disease. In APOA1(-75)-APOA1(+83) bilocus haplotypes, G-M2(+) was associated (P=0.0001) with very high risk (OR 3.173, 95% CI 1.774 to 5.674) for gallstone disease in males only. APOA1(-75)-APOC3(SstI) haplotypes also showed significant association while APOA1(+83)-APOC3(SstI) haplotypes showed no association with gallstone disease. CONCLUSIONS: The APOA1 -75 G/A polymorphism is associated with gallstone disease and shows sex-specific differences. On the other hand, APOA1 M2(+/-) and APOC3 SstI polymorphisms may not be associated with gallstone disease. Haplotype analysis is a better predictor of risk for gallstone disease. PMID- 17853952 TI - Usefulness and impact on management of positive and negative capsule endoscopy. AB - OBJECTIVE: To determine the usefulness of positive and negative capsule endoscopies (CEs), and the impact of each on short- and long-term patient management. METHODS: Medical records were reviewed for 70 consecutive CE patients. Based on outcomes from referring physicians, it was determined whether CE was useful, partially useful or not useful at all in the overall patient management, and whether CE assisted in providing a diagnosis, and impacted on short-term long-term management. RESULTS: CE indications included overt bleeding (37%), occult bleeding (20%), iron deficiency (17%), abdominal pain and weight loss (13%), assessing the extent of or confirming a diagnosis of Crohn's disease (9%) and screening for familial adenomatous polyposis (4%). Positive studies were seen in 58% of overt bleeds, 50% of occult bleeds, 33% of iron deficiencies and 33% of Crohn's diseases. Overall, 28 studies (40%) were positive studies and 42 (60%) were negative studies. CE aided in diagnosis in 11 of 28 (39%) positive and 12 of 42 (29%) negative studies (P=0.35). Positive and negative CEs had an impact on short-term management in 12 of 28 (43%) versus 18 of 42 (43%) cases, respectively (P=1.0), and on long-term management in 14 of 28 (50%) versus 15 of 42 (36%) cases, respectively (P=0.23). For positive and negative studies, respectively, CE was considered useful in 12 of 28 (43%) versus 15 of 42 (36%) cases (39% overall), partially useful in 10 of 28 (36%) versus 10 of 42 (24%) cases (28% overall), and not useful at all in six of 28 (21%) versus 17 of 42 (40%) cases (33% overall). CONCLUSIONS: Although a negative CE may aid in making a definitive diagnosis in only 29% of patients, its effect on management and overall usefulness is similar to that of a positive CE. A physician's decision on whether to order CE should not be based solely on the pretest probability of a positive examination but also on the clinical utility of a negative study. PMID- 17853953 TI - Granuloma-positive Crohn's disease. AB - BACKGROUND: The epithelioid granuloma is a characteristic histological feature of Crohn's disease. In some pathological classification schemes, the criteria for a definite, probable or possible diagnosis have been listed, with the epithelioid granuloma indicating definite Crohn's disease. METHODS: In the present evaluation, 247 prospectively evaluated Crohn's disease patients (24.3%), from a consecutively accumulated population database of 1015 patients, were found to have an epithelioid granuloma. The recently devised Montreal classification for Crohn's disease was then applied to this granuloma-positive cohort of Crohn's disease patients to define age at diagnosis for men and women, disease site and disease behaviour. RESULTS: The investigation showed that patients with Crohn's disease and granulomas were most often diagnosed early in the course of their disease, particularly women. Their disease was often extensive, with ileocolonic and upper gastrointestinal tract involvement. Finally, disease behaviour was most often complex, especially with penetrating disease complications. CONCLUSION: Using homogeneous (ie, 'reagent-grade') patient cohorts defined by a recently devised classification method for Crohn's disease, the study demonstrated that an epithelioid granuloma may represent a histopathological marker for an early biological event in the etiopathogenesis of Crohn's disease, and this may have predictive significance with respect to the location and clinical behaviour of Crohn's disease. PMID- 17853954 TI - Complementary and alternative medicine use by patients chronically infected with hepatitis C virus. AB - Complementary and alternative medicine (CAM) is becoming increasingly popular in North America. The use of CAM is also popular in patients with chronic liver disease but is not well documented. The extent of use of CAM in chronic hepatitis C virus (HCV) infected patients was determined, and the demographic and clinical data between users and nonusers of CAM was compared. Seventy-six patients (30% female) with chronic HCV were interviewed. The mean age was 43+/-8 years. Current use of CAM for HCV was reported by 35 of 76 patients (46%). Eighteen of 76 patients within this group used herbal supplements (24%). The most commonly used herb was Silybum marianum (milk thistle), reported by 10 of 76 patients (13.2%). Commonly reported benefits of CAM use included reduction in fatigue, boost in the immune system and improved gastrointestinal function. No adverse effects of CAM use were reported. In the present study, four of 18 patients (22%) with chronic liver disease taking herbal therapies were on herbs that increased bleeding time. The use of CAM in chronic HCV patients is significant. Patients should be asked specifically about their use of CAM. CAM use may have implications affecting conventional treatment and management of HCV. PMID- 17853955 TI - New endoscopic techniques for obscure gastrointestinal bleeding. AB - The case of a postmenopausal woman with a congenital aortic stenosis is presented. She presented with severe iron deficiency anemia. After negative extensive gastrointestinal analysis, she was treated with octreotide for six months. After cessation of octreotide, anemia rapidly recurred. A second capsule endoscopy and a double balloon enteroscopy were performed, and an intestinal vascular malformation was found. After surgical segment resection, the patient had stable, normal levels of hemoglobin and no complaints after 14 months of follow-up. PMID- 17853956 TI - Pylephlebitis and pyogenic liver abscesses: a complication of hemorrhoidal banding. AB - Hemorrhoidal banding is a well-established and safe outpatient procedure. Septic complications of hemorrhoidal banding are rare but can be fatal. The first case of pylephlebitis (septic portal vein thrombosis) and pyogenic liver abscess following hemorrhoidal banding in a 49-year-old man with diabetes is reported in the present study. Risk factors, management and the role of prophylaxis in immunocompromised patients are discussed. Caution against hemorrhoidal banding in immunosuppressed patients, including patients with diabetes, is warranted. PMID- 17853957 TI - Pursuing efficiency: international visibility of the scientific production of Brazilian graduate programs in child and adolescent health from 1998 through 2003. AB - OBJECTIVE: To assess the trend in the number of published articles by Brazilian graduate programs in child and adolescent health and the proportion of such publications cited in MEDLINE and Thomson Scientific's Journal Citation Reports (JCR), using the former database as a proxy for efficiency and the latter as an indicator of visibility. METHODS: We assessed the trends of 14 graduate programs concerning the number of theses, dissertations, and articles cited in MEDLINE and JCR, through secondary data from the latest two triennial evaluations carried out by the Brazilian Federal Agency for the Improvement of Higher Education (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, CAPES) between 1998 and 2000 and between 2001 and 2003). RESULTS: The number of published articles increased (1,520 to 1,917), as did the median number of articles cited both in MEDLINE (32.5 to 45) and in JCR (24.5 to 27). The median number of dissertations rose from 19.5 to 26.5; the median number of theses went up from 12 to 13.5. The median number of faculty advisors decreased (21.5 to 18.4). CONCLUSION: Graduate programs in child and adolescent health became more efficient in producing knowledge through the publication of more articles with broader international visibility. Such trend was contradictorily accompanied by a diminishing number of advisors. PMID- 17853959 TI - [The neurologist when faced with stroke]. AB - The role of the neurologist during the entire care process involving patients who suffer a stroke is stressed. His/her intervention in this process is of fundamental importance given the existence of widely verified scientific evidence that this significantly improves the survival expectancies and the independence of these patients and that it is profitable for the health care system. An improvement in the quality of life of both the patients and their family is obtained from this intervention. PMID- 17853958 TI - Impact of rubella vaccination strategy on the occurrence of congenital rubella syndrome. AB - OBJECTIVE: Routine rubella vaccination was introduced in Paraiba, northeastern Brazil, through a catch-up campaign targeting children aged 1-11 years, in 1998. A campaign among women of childbearing age was conducted in 2001. We describe the epidemiology of rubella and congenital rubella syndrome (CRS) in the state of Paraiba between 1999 and 2005. METHODS: Rubella and CRS surveillance data for the 1999-2005 period were analyzed. Suspected cases of rubella were confirmed by laboratory findings, epidemiological link, or clinical data. International standardized CRS definitions were used. RESULTS: Of 5,924 suspected cases of rubella between 1999 and 2005, 1,266 (21%) were confirmed, 766 (61%) by laboratory findings. During a rubella epidemic in 2000 (18.8/100,000), the incidence among individuals aged 14-19 years (42/100,000) had a fourfold increase relative to children aged 1-13 years (95% confidence interval = 3.2-5.1). The overall rubella incidence was 0.9/100,000 in 2005. Of 177 suspected cases of CRS between 1999 and 2005, 167 (94%) were tested for IgM. Of 14 (8%) laboratory confirmed cases of CRS, 12 (86%) were born in 2001, with an incidence of 0.2/100,000 children aged less than 1 year. CONCLUSIONS: The 1998 rubella vaccination campaign was insufficient to prevent an outbreak among young adults in 2000, with a high CRS incidence in 2001. Between 2002 and 2005 the incidence of rubella and CRS decreased; however, high routine vaccination coverage and high quality surveillance remain critically important to achieve CRS elimination by 2010. PMID- 17853960 TI - [Transthoracic echocardiography in stroke performed by neurologist: pilot study]. AB - INTRODUCTION: The aim of this study is to assess concordance between transthoracic echocardiography (TTE) performed by neurologists and cardiologists for the screening of cardioembolic sources in patients with ischemic stroke. METHODS: We examined prospectively 27 consecutive patients with ischemic stroke. A potential source of embolism in all of the patients was sought by means of a TTE study. This study was performed by one neurologist after one-month full-time training on the technique and independently by one cardiologist whose results were considered as the reference standard. Regarding the risk of cardioembolism, findings from TTE studies were considered as normal, or indicative of either moderate or high risk, according to the TOAST criteria. Agreement between the two observers on the diagnosis of cardioembolic source was analyzed with the Cohen's Kappa Test (K). A K > 0,6 was considered as good agreement. RESULTS: The 27 patients studied had a mean age of 68,7 +/- 10,2 years and 70 % were men. A cardioembolic source was detected in 9 patients by the cardiologist and 8 of these were also identified by the neurologist: in 1 patient a mitral annulus calcification was not detected in the examination performed by the neurologist. In 2 patients with poor echocardiographic window, the neurologist underestimated the left ventricular function. Diagnostic agreement between both examinations was 88,9 % (K: 0,77; p = 0,001). CONCLUSION: Compared with cardiologists, trained neurologists show a fairly high degree of accuracy in the TTE screening of patients with stroke. Those cases with poor echocardiographic window or with abnormal findings should be confirmed by the cardiologists. PMID- 17853961 TI - [Influence of previous diagnosis of diabetes mellitus in the stroke severity and in-hospital outcome in acute cerebral infarction]. AB - INTRODUCTION: To analyze if previous diagnosis of diabetes influences stroke severity and in-hospital outcome in acute cerebral infarction (CI) patients. METHODS: Observational study between 1998-2004 with inclusion of consecutive patients with CI. Risk factors, stroke subtype, severity on admission (Canadian Stroke Scale [CSS]), in-hospital complications, mortality, length of stay and stroke outcome (modified Rankin Scale [mRS]) in CI patients with and without previous diagnosis of diabetes were compared. RESULTS: A total of 2,213 consecutive acute stroke patients; 661 with previous history of diabetes (29,9%) were included. These patients were older, had more rate of hypertension, dyslipidemia, coronary arterial disease, peripheral vascular disease and previous stroke than non-diabetic patients. Atherotrombotic and lacunar infarction were more frequent in diabetic patients. They also had more in-hospital complications as urinary tract infection (4.7 % vs 2.6 %; p < 0.05), multiple organ dysfunction syndrome (3.3% vs 1.8%; p<0.05), deteriorating stroke (6.1 % vs 3.4 %; p < 0.01), recurrent stroke (3.3% vs 1.7%; p<0.05) and increase of infarction volume (2.6 % vs 1.1%; p<0.05), with no differences in stroke severity at admission, mortality, length of in-hospital stay and stroke outcome. Previous history of diabetes was independently associated with in-hospital complications (OR: 1.377; CI 95%: 1.053 1.799). CONCLUSIONS: Previous diagnosis of diabetes is not associated by itself to higher stroke severity on admission although a greater risk of in-hospital complications is found. PMID- 17853962 TI - [Recommendations of the use of transcranial Doppler to determine the existence of cerebral circulatory arrest as diagnostic support of brain death]. AB - INTRODUCTION: The clinical criteria for brain death consist of the demonstration of the absence of any clinical sign of encephalic activity. Confirmatory testing is usually not required for the diagnosis of brain death, except in some special situations that the Spanish law details. In these situations demonstrating cerebral circulatory arrest (CCA) by cerebral flow studies is necessary to support the diagnosis of brain death. OBJECTIVE: To review the use of transcranial Doppler ultrasonography (TCD) for confirming brain death and to establish uniform criteria for the routine use of TCD as a confirmatory test. METHODS: Based on literature analysis, the authors developed the guidelines for performance and interpretation of TCD in clinically brain-dead patients, in order to confirm the diagnosis. The active members of the Spanish Neurosonology Society (SONES) reviewed an initial draft, until a consensus was reached. RESULTS: In a clinically brain-dead patient, specific intracranial flow patterns indicating CCA can be visualized by TCD. The specific flow patterns are the presence of reverberating flow and/or systolic spikes, and should be detected in both middle cerebral arteries and also in the basilar artery. We recommend to repeat the examination within 30 minutes to confirm the findings. CONCLUSIONS: TCD is a useful method detecting CCA and therefore can be used to confirm brain death in a clinically brain-dead patient. The presence of reverberating flow, systolic spikes or absence of flow in the basilar and both middle cerebral arteries observed in two examinations is highly specific for the prediction of CCA and brain death in all patients. PMID- 17853963 TI - [Biological markers in spontaneous intracerebral hemorrhage]. AB - After intracerebral hemorrhage, some molecular processes, such as coagulation cascade activation and neuroinflammation appear which leads to a secondary brain damage. All this has a poor life and functional prognosis in many of the patients. This paper aims to review the literature available regarding these processes and the use of biological markers that make it possible to obtain better knowledge and management of this disease. PMID- 17853964 TI - [Stroke unit: a cost-effective care need]. AB - INTRODUCTION: The development of stroke units (SU) has supposed a landmark in cerebrovascular diseases management. However, the high scientific evidence level in which the recommendations of attendance of acute stroke patients in SU do not correspond to the level of SU implantation. METHODS: Review of the published studies on SU, with special attention to those demonstrating their efficacy and effectiveness. Finally, we will try to give answers to several open questions regarding the SU practical issues. RESULTS: Stroke units are the stroke care model more efficacious in comparison with stroke teams as well as with non neurological assistance. Every stroke patient can benefit from SU care. These units are efficient, cost-effective and their benefits are consistent with time or operation. When comparing to other specific stroke therapies as aspirin or intravenous thrombolysis, SU have higher target population and higher benefit in terms of number of deaths or dependences avoided. News approaches in SU management as the implementation of noninvasive monitoring or clinical pathways could even improve their benefits. CONCLUSIONS: Stroke units are a cost-effective stroke care need, and they should be consider as a sanitary priority. PMID- 17853965 TI - [Intracranial hemorrhages as first manifestation of acute myeloid leukemia]. PMID- 17853966 TI - [Massive spinal epidural hematoma]. PMID- 17853967 TI - [Cerebral ischemia as first manifestation of paroxysmal nocturnal hemoglobinuria]. AB - INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disease characterized by chronic intravascular hemolysis, cytopenia and increased tendency to thrombosis. Arterial thrombosis has been observed in patients with PNH but is uncommon compared with venous thrombosis. Cerebral arterial thrombosis has been anecdotally described as the first clinical manifestation of PNH. CASE DESCRIPTION: We present the case of a 48-yearold male who was admitted because of high-grade fever and infarction in the left middle cerebral artery territory. Other associated findings were mild anemia (hemoglobin level: 10.1 g/dl), renal ischemia and intra-abdominal venous thrombosis. Recurrent arterial and venous thromboembolic events were observed during his hospital stay. The diagnosis of PNH was confirmed by flow cytometric analysis. CONCLUSIONS: PNH is a rare cause of cerebral ischemia and it should be considered in stroke patients with abnormal blood findings or marked prothrombotic tendency. We discuss the treatment guidelines and prevention of thrombotic complications. PMID- 17853968 TI - [Involuntary movements in brainstem ischemic lesions]. AB - INTRODUCTION: The appearance of movement disorders in vascular disease of the brainstem has hardly been described in the literature. Its frequency is probably underestimated due to their briefness and that they are often misinterpreted as epileptic seizures. Their pathophysiological mechanism is uncertain. Several mechanisms, such as the existence of a seizure-generating brainstem center, capable of generating epileptic activity or the interruption of the corticospinal tracts due to ischemia, have been proposed. CLINICAL CASES: We present three patients with disease of the basilar artery and extensive brainstem infarction who have the presentation of sudden, involuntary movements in limbs in the initial phase, in paroxysms of short duration and of varied semiology in common. We described this in all of them. An electroencephalographic functional study during these episodes was done in one of the cases. CONCLUSIONS: Preservation of conscious level, its variability of presentation, the null response to antiepileptic drugs and normality of the electroencephalogram in one of them leads us to ratify the hypothesis of failure of the cortical inhibitory projections as subcortical centers in trunk or spinal cord as pathophysiological origin of these involuntary movements. We stress the importance of recognizing these clinical manifestations of appearance in the initial phases of the disease, that permit a rapid diagnosis with the help of the transcranial Doppler to establish an early and aggressive treatment of this disease having known seriousness and bad prognosis. Further prospective studies would be interesting to know what the real incidence of these movements is, and functional ones to clarify the pathophysiological nature of this phenomenon. PMID- 17853969 TI - [Hemiparkinsonism secondary to mesencephalic bleeding]. AB - Vascular parkinsonism is the second cause of secondary parkinsonism, and can cause a complex clinical syndrome. In spite of this, it is not common to find an isolated vascular injury in the mesencephalic region, and even rarer for it to give rise to clinical parkinsonism. We present the case of a young patient who developed left hemiparkinsonism with a fluctuating clinical evolution and unpredictable response to the treatment after suffering right mesencephalic bleeding. Structural and functional neuroimaging techniques showed injury on the mesencephalic level and no uptake in the right striatal region, respectively. PMID- 17853970 TI - [A new Spanish family with CADASIL associated with 346C>T mutation of NOTCH3 gene]. AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult-onset inherited condition characterized by migraine, recurrent strokes, and subcortical dementia. Other manifestations as psychiatric disturbances, seizures, hypoacusia or learning disorders have been reported. CADASIL may be suspected based on clinical syndrome, a positive family history, and a typical cranial magnetic resonance image with T2/FLAIR hyperintense signals in the temporopolar white matter or the external capsule. Bilateral white matter abnormalities are invariably seen and often small subcortical infarcts are also present. Accumulation of the granular osmiophilic material on skin biopsy may help in diagnosis. Mutations in the NOTCH3 gene localized in chromosome 19 are involved in its pathogenesis. Only 11 families from Spain have been reported. Here we describe two members of a family with clinical symptoms and neuroimaging of CADASIL. The skin biopsy was negative. In both patients 346C>T mutation in exon 3 of NOTCH3 gene was found. There is the first Spanish family reported with CADASIL, caused by the 346C > T mutation in NOTCH3 gene which was frequently described in the European series. PMID- 17853971 TI - [Lobar cerebral hemorrhage due to infectious endocarditis with aortic root abscess due to Streptococcus viridans]. PMID- 17853972 TI - [Consideration on cyclic alternating pattern]. PMID- 17853974 TI - [An evaluation of some of the relationships between thought-action fusion, attributional styles, and depressive and obsessive-compulsive symptoms]. AB - OBJECTIVE: Thought-action fusion (TAF) is a cognitive bias presumed to underlie the development of obsessional problems. Two domains of TAF have been identified. The first, TAF-moral, is characterized by the belief that having morally unacceptable thoughts is as bad as actually carrying them out. The second, TAF likelihood, refers to the belief that certain thoughts cause particular events. The event can be related to one's self (likelihood-self) or to someone else (likelihood-others). The other cognitive variable of the study is attributional style. The theory of attributional styles, in terms of the causes of good and bad events, is taken into account especially in the context of depression and has four dimensions: internality-externality, stability-instability, globality specifity, and importance-unimportance. The first objective of the present study was to investigate the relationships between TAF, and attributional style, and depressive and obsessive-compulsive symptoms. The second objective was to determine the predictors of TAF when the effects of depressive and obsessive compulsive symptoms are statistically controlled. METHOD: The sample consisted of 312 students randomly selected from different departments at Hacettepe University. The Thought-Action Fusion Scale (TAFS), Attributional Style Questionnaire (ASQ), Maudsley Obsessive-Compulsive Inventory (MOCI), and Beck Depression Inventory (BDI) were administered to these students. RESULTS: The correlations among all the subtypes of TAF (TAF-moral, likelihood-self, and likelihood-others), and the global attributions for bad events, BDI, and MOCI were significant. In addition, the correlation between TAF-moral and the importance of the attribution for bad events was significant. TAF-likelihood others and TAF-likelihood-self were predicted by global attributions for bad events and TAF-moral was predicted by the importance of the attributions for bad events. CONCLUSION: TAF, and attributional styles, and depressive and obsessive compulsive symptoms may be related to each other. The results also suggest a possible effect of other variables not controlled in this study, both on TAF and the dimensions of attributional styles. PMID- 17853975 TI - [Sociodemographic and clinical factors associated with compliance to methylphenidate treatment in children with attention deficit hyperactivity disorder]. AB - OBJECTIVE: The present study aimed to determine the rate of treatment compliance in children with attention deficit hyperactivity disorder (ADHD) that were newly prescribed methylphenidate, and to evaluate the associated clinical and sociodemographic factors, as well as parental concerns about drug treatment. METHOD: The sample of this prospective and observational study consisted of 238 children aged 7-18 years with ADHD diagnosed according to DSM-IV criteria. At the end of the first year, the study sample was splitted into 2 groups; compliant and non-compliant. Parental attitudes toward drug therapy, and clinical and sociodemographic characteristics of the 2 groups were compared. A clinician rated parental concerns about drug treatment 4-6 weeks after the interview that was conducted in order to inform them about methylphenidate therapy. Regarding a minimum requirement of 5 days weekly dosage and drug holidays, cases that took more than 70% of the recommended methylphenidate dose at the end of the first year were described as compliant. RESULTS: At the end of the first year of treatment, the drug compliance rate was 80.3% (n= 191). The non-compliant group consisted of older children. A significant difference was observed between the compliant and non-compliant groups in terms of parental approach toward drug treatment. Children in the non-compliant group had parents that had doubts about pharmacotherapy and these children were less compliant with methylphenidate treatment. CONCLUSION: Parental concerns about methylphenidate treatment in ADHD may influence treatment compliance. Additionally, it is suggested that developmental psychological characteristics associated with adolescence may also be important. PMID- 17853976 TI - [The symptomatology and prevalence of symptoms of premenstrual syndrome in Manisa, Turkey]. AB - OBJECTIVE: The aim of this study was to investigate the prevalence of premenstrual syndrome (PMS) symptoms, the frequency and severity of the symptoms, and their association with sociodemographic variables in fertile women between the ages of 15 and 49 years. METHOD: The study included 541 women living in the area of the 7th Primary Health Care Center of Manisa, Turkey. Face-to-face interviews were conducted and a sociodemographic data form, a DSM-IV diagnostic criteria form, and the premenstrual evaluation form (PEF) were administered. In the analysis of the data, K-means cluster analysis was performed and cluster analysis with 3 categories according to the severity was used. In the evaluation of the 18 subscales possible maximum variation quotient is obtained by dividing the maximum possible PEF score to the scores the subjects got. In the group comparison analyses, chi-square test for the categorical variables, and t-test for continuous variables were used. RESULTS: Among the study group, 6.1% had severe PMS symptoms and 72.2% of these women had some dysfunction as defined by DSM-IV. The most common symptoms were feeling irritable and restless (72%), anxiety (67.3%), feeling fullness, discomfort or pain in the abdomen (66.6%), lack of energy or easily fatigued (66.6%), and fatigue in the legs (65.5%). CONCLUSION: The prevalence of the risk of PMS was 6.1%. The most common and severe PMS symptoms were feeling irritable and restless. PMID- 17853977 TI - [Long term follow-up of patients with postpartum psychosis]. AB - OBJECTIVE: This research compared the demographic features, presence of confusion, and long-term follow-up results of women with postpartum psychosis to control subjects. METHOD: The study included 23 patients with symptoms that emerged in the six-month period after delivery who were followed-up between 1998 and 2006. The control group consisted of 25 age- and education level-matched female patients experiencing their first psychotic episode. Data were collected with a sociodemographic questionnaire, the Clinical Global Impression Scale, and the Delirium Rating Scale. Final diagnoses were made according to DSM-IV. RESULTS: Among the postpartum women, 73.9% developed psychosis during their first parturition. The postpartum psychosis and control groups were followed-up for 4.00 +/- 1.62 (range: 2-6) and 3.96 +/- 1.24 (range: 2-6) years, respectively. During the follow-up period, 21.7% of the postpartum patients developed a mood disorder, and 77.9% developed schizophrenia and other psychotic disorders. Among those in the control group, 32.0% were diagnosed with a mood disorder and 68.0% with schizophrenia and other psychotic disorders. The distribution of final diagnoses in the 2 groups were similar. Patients with postpartum psychosis experienced more confusion than the control subjects. During the follow-up period, 65.2% of the patients with postpartum psychosis and 72% of the control patients had recurrence. CONCLUSION: The course of postpartum psychosis was similar to DSM-IV diagnostic criteria, except for the presence of confusion. During the follow-up period, most of the patients in both groups were diagnosed with schizophrenia and other psychotic disorders. This result indicated that there is no need for other diagnostic criteria for postpartum psychosis other than those presently contained in DSM-IV. PMID- 17853978 TI - [Anger expression on the road: validity and reliability of the driving anger expression inventory]. AB - PURPOSE: The purpose of the current study was to check the validity and reliability of DAX (The Driving Anger Expression Inventory) in a Turkish population. METHOD: The study included 220 randomly chosen drivers between the ages of 20 and 65 years from Ankara, Istanbul, and Samsun. The assessment instruments were DAX, The Driving Anger Scale, Brief Symptom Inventory, and the anger symptoms dimension, anger reactions dimension, and anger-eliciting situations dimension of the Multidimensional Anger Scale. RESULTS: Psychometric analyses of the scale showed that the Turkish-adapted DAX has the same factor structure and, like the original DAX, consists of 4 subscales and 1 index. The analyses revealed that male drivers between 21 and 30 years old reported more physically aggressive expression and that they used their vehicle to express anger, whereas female drivers reported more adaptive/constructive expression. Furthermore, it was found that drivers who were university graduates expressed their anger verbally when driving, while drivers who were primary and secondary school graduates expressed anger physically. Regression analyses showed that traffic violation penalty, police presence, discourteous or disrespectful behavior to other drivers, and driving slow were predictive variables for total aggressive expression (verbal, physical aggressive expression, and using of the vehicle to express anger). CONCLUSION: The current study revealed that the Turkish version of DAX might be a valid and reliable scale to measure forms of anger expression related to driving and important signs related to coping with driving-related anger were identified. Furthermore, it can be suggested that DAX could be used as an assessment instrument for driver selection, and it can be used during the psycho-technical assessment procedure. PMID- 17853979 TI - [Psychometric properties of the defense style questionnaire: a reliability and validity study]. AB - OBJECTIVE: To examine the psychometric properties of the Turkish form of the Defense Style Questionnaire (DSQ). METHOD: The study included 190 participants, of which 85 with a depressive disorder or obsessive-compulsive disorder diagnosis composed the clinical group, and 105 individuals without any psychiatric diagnosis composed the control group. Participants completed the DSQ, Beck Depression Inventory (BDI), and Trait Anxiety Scale (TAS). RESULTS: As for the psychometric properties of the DSQ-40, the internal consistency of the mature, neurotic, and immature defense styles was 0.70, 0.61, and 0.83, respectively. Additionally, results revealed that the 3 defense styles had acceptable split half reliability and test-retest reliability coefficients. Considering the concurrent validity, the mature defense style was negatively correlated with the symptoms of depression and anxiety, whereas the immature defense style was positively correlated with these symptoms. The neurotic defense style, on the other hand, had a positive correlation with anxiety symptoms, but did not reveal a significant correlation with depressive symptoms. The examination of criterion validity revealed results were consistent with our expectations. Significant differences were found in the expected direction between the control and clinical groups. CONCLUSION: The psychometric properties of DSQ-40 seem to be quite acceptable; therefore, this questionnaire can be utilized for research purposes. PMID- 17853980 TI - [Reliability and validity studies of Turkish translation of Eysenck Personality Questionnaire Revised-Abbreviated]. AB - OBJECTIVE: The aim of the present study was to examine the reliability and the validity of the Turkish translation of the Eysneck Personality Questionnaire Revised-abbreviated Form (EPQR-A) (Francis et al., 1992), which consists of 24 items that assess neuroticism, extraversion, psychoticism, and lying. METHOD: The questionnaire was first translated into Turkish and then back translated. Subsequently, it was administered to 756 students from 4 different universities. The Fear Survey Inventory-III (FSI-III), Rosenberg Self-Esteem Scales (RSES), and Egna Minnen Betraffande Uppfostran (EMBU-C) were also administered in order to assess the questionnaire's validity. The internal consistency, test-retest reliability, and validity were subsequently evaluated. RESULTS: Factor analysis, similar to the original scale, yielded 4 factors; the neuroticism, extraversion, psychoticism, and lie scales. Kuder-Richardson alpha coefficients for the extraversion, neuroticism, psychoticism, and lie scales were 0.78, 0.65, 0.42, and 0.64, respectively, and the test-retest reliability of the scales was 0.84, 0.82, 0.69, and 0.69, respectively. The relationships between EPQR-A-48, FSI-III, EMBU-C, and RSES were examined in order to evaluate the construct validity of the scale. Our findings support the construct validity of the questionnaire. To investigate gender differences in scores on the subscales, MANOVA was conducted. The results indicated that there was a gender difference only in the lie scale scores. CONCLUSIONS: Our findings largely supported the reliability and validity of the questionnaire in a Turkish student sample. The psychometric characteristics of the Turkish version of the EPQR-A were discussed in light of the relevant literature. PMID- 17853981 TI - [Prefrontal cortex: implications for memory functions and dementia]. AB - OBJECTIVE: The prefrontal cortex (PFC), which is one of the most complex areas of the human brain, is a frontal lobe segment that is consistently implicated in motor behaviors. In recent years it has been suggested that it is involved in memory functions via its diffuse anatomical networks. In this review, it was aimed to summarize the recent literature about PFC neuroanatomy, and its role in memory, normal aging, and dementias. METHOD: We retrospectively reviewed the literature, including recent relevant studies. In addition, textbooks were included for essential themes. PubMed and the Google search engine were used, and the keywords chosen for searches were: prefrontal cortex, dementia/types, and memory. RESULTS: Although the PFC has considerable cognitive and social functions, only minor cognitive dysfunction is observed when the frontal lobes are severely damaged. It is possible to say that the memory deficits could be masked by rigorous behavioral symptoms. The PFC has a critical role in memory retrieval. There is growing evidence that the PFC is involved not only in frontal lobe-type dementias, but also Alzheimer disease, mild cognitive impairment, and normal aging. The psychiatric and behavioral symptoms in such cases may be related to PFC dysfunction. CONCLUSION: Memory-related disorders are commonly associated with the frontal lobes and PFC. It may be considered that different parts of the PFC are related to different memory types and memory dysfunctions. Further studies with advanced neuroimaging techniques and valid animal models for all types and stages of dementias will help us to understand the role of the PFC in memory, physiology, and pathologies. PMID- 17853982 TI - [Therapeutic response to plasmapheresis in four cases with obsessive-compulsive disorder and tic disorder triggered by streptococcal infections]. AB - The acronym PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been assigned to a subgroup of patients experiencing pediatric onset obsessive-compulsive symptoms and tics as a result of autoimmune response to group A beta-hemolytic streptococcal infection. It has been hypothesized that an immune process initiated by infection affects the basal ganglia and causes neuropsychiatric symptoms. In cases with severe neuropsychiatric symptoms, the use of treatment strategies that interrupt the autoimmune process responsible for the pathogenesis of PANDAS, such as therapeutic plasmapheresis or intravenous immunoglobulin, has been proposed. In this paper, we discuss the effect of plasmapheresis treatment in 4 adult cases of obsessive-compulsive disorder and tic disorder triggered by streptococcal infections. PMID- 17853983 TI - [Charles-Bonnet Syndrome: a report of two cases]. AB - Charles-Bonnet syndrome (CBS) occurs after the loss of vision or a decrease in visual ability and is characterized by visual hallucinations with insight and preserved cognitive status. In this paper, 2 cases in which vision was lost (in one patient due to hypophyseal macroadenoma and in the other due to diabetic retinopathy) are presented. The first case is a 35-year-old male referred to the psychiatry department for depressive complaints. He lost his vision due to optic atrophy following multiple surgeries for hypophyseal macroadenoma and visual hallucinations developed afterwards. Ziprasidone 80 mg/day was started and the hallucinations disappeared on the fifth day, but the medication had to be withdrawn because of severe vascular type headaches. Olanzapine 5 mg/day was subsequently used without benefit. He refused further medication and the visions gradually changed into sparkling lights and simple figures at the 7-month follow up. The second case was a 54-year-old woman with a 20-year history of type-II diabetes mellitus. Visual hallucinations developed after bilateral visual loss due to diabetic retinopathy 4 years earlier. She responded well to treatment with quetiapine 100 mg/day and paroxetine 20 mg/day. Neither of the cases had reported their visual symptoms to their physicians; the second case was diagnosed after 4 years by active screening. Both of the cases had neuroanatomic lesions. CBS symptoms should be screened actively in patients with visual loss and physicians should be educated about diagnosing CBS. Novel antipsychotics, such as ziprasidone and quetiapine, seem to be effective alternatives for the treatment of CBS. PMID- 17853984 TI - [Two cases of koro syndrome or anxiety disorder associated with genital retraction fear]. AB - As a cultural-bound syndrome, koro is described in the DSM-IV as "an episode of sudden and intense anxiety that the penis (or, in females, the vulva and the nipples) will recede into the body and possibly cause death." Sometimes the syndrome may occur as an epidemic involving several hundreds to thousands of subjects within a short period of time. While the syndrome individually involves an anxiety reaction and fear of mortal genital retraction, it collectively takes the form of epidemics and mass panic. Recently a consensus has been reached about the fact that genital retraction is intimately related not only with ethno cultural beliefs but also with the dramatic expression of acute anxiety and fear of impending catastrophe or death. We present two cases of koro syndrome who experienced severe anxiety due to the feeling of genital retraction and thus we question the cultural specifity of fears of genital retraction. PMID- 17853985 TI - Sex in the morning or in the evening? Females adjust daily mating patterns to the intensity of sexual harassment. AB - Selection on males to mate at a higher rate than females often results in male harassment of females and counteracting female responses. When the reproductive value of copulation changes over time, these mating strategies are expected to be time dependent. Here, we demonstrate that variation in the intensity of male harassment leads to drastic changes in female daily mating patterns. In feral populations of fowl Gallus gallus domesticus, male harassment is intense, particularly in the evening when inseminations are most likely to result in fertilization. We experimentally manipulated the intensity of male harassment through similar-sized groups of different sex ratios. Male mating propensity was always higher than females', particularly in male-biased groups and in the evening, when males were closer to and more likely to approach females. Females counteracted male harassment by escalating resistance to mating and--crucially- by shifting their daily mating pattern: in strongly female-biased groups with relaxed sexual harassment, females solicited sex in the evening, while in male biased groups, they solicited sex in the morning, thus avoiding harassment in the evening. Together, these results indicate that intersexual conflict may occur not only over mating rates but also over when in the day to copulate. PMID- 17853986 TI - Worker reproduction in Formica ants. AB - A potential tragedy of the commons arises in social-insect colonies where workers are fertile if egg-laying workers decrease their contribution to other tasks. We studied worker ovary development and egg laying in relation to kin structure, colony size, and the presence of a queen in nine species (11 populations) of Formica ants. Workers were highly fertile and laid eggs in the presence of a queen in five out of the seven species where egg samples were obtained. Worker fertility correlated neither with colony size nor with kin structure, which suggests that colony-level costs and efficiency of policing precede relatedness as the most important conflict determinant. We conclude that careful quantification of the costs of worker reproduction and policing is essential for inferences about the tragedy of the commons. PMID- 17853987 TI - Waiting for invasions: a framework for the arrival of nonindigenous species. AB - The process of nonindigenous species (NIS) arrival has received limited theoretical consideration despite importance in predicting and preventing the establishment of NIS. We formulate a mechanistically based hierarchical model of NIS arrival and demonstrate simplifications leading to a marginal distribution of the number of surviving introduced individuals from parameters of survival probability and propagule pressure. The marginal distribution is extended as a stochastic process from which establishment emerges with a waiting time distribution. This provides a probability of NIS establishment within a specified period and may be useful for identifying patterns of successful invaders. However, estimates of both the propagule pressure and the individual survival probability are rarely available for NIS, making estimates of the probability of establishment difficult. Alternatively, researchers are able to measure proportional estimates of propagule pressure through models of NIS transport, such as gravity models, or of survival probability through habitat-matching indexes measuring the similarity between potentially occupied and native NIS ranges. Therefore, we formulate the relative waiting time between two locations and the probability of one location being invaded before the other. PMID- 17853988 TI - Sexual selection and trichromatic color vision in primates: statistical support for the preexisting-bias hypothesis. AB - The evolution of trichromatic color vision in primates may improve foraging performance as well as intraspecific communication; however, the context in which color vision initially evolved is unknown. We statistically examined the hypothesis that trichromatic color vision in primates represents a preexisting bias for the evolution of red coloration (pelage and/or skin) through sexual selection. Our analyses show that trichromatic color vision evolved before red pelage and red skin, as well as before gregarious mating systems that would promote sexual selection for visual traits and other forms of intraspecific communication via red traits. We also determined that both red pelage and red skin were more likely to evolve in the presence of color vision and mating systems that promote sexual selection. These results provide statistical support for the hypothesis that trichromatic color vision in primates evolved in a context other than intraspecific communication with red traits, most likely foraging performance, but, once evolved, represented a preexisting bias that promoted the evolution of red traits through sexual selection. PMID- 17853989 TI - Strong reciprocity or strong ferocity? A population genetic view of the evolution of altruistic punishment. AB - Strong reciprocity, defined as a predisposition to help others and to punish those that are not helping, has been proposed as a potent force leading to the evolution of cooperation and altruism. However, the conditions under which strong reciprocity might be favored are not clear. Here we investigate the selective pressure on strong reciprocity by letting both limited dispersal (i.e., spatial structure) and recombination between helping and punishment jointly determine the evolutionary dynamics of strong reciprocity. Our analytical model suggests that when helping and punishment are perfectly linked traits (no recombination occurring between them), strong reciprocity can spread even when the initial frequency of strong reciprocators is close to 0 in the population (i.e., a rare mutant can invade). By contrast, our results indicate that when recombination can occur between helping and punishment (i.e., both traits coevolve) and is stronger than selection, punishment is likely to invade a population of defectors only when it gives a direct fitness benefit to the actor. Overall, our results delineate the conditions under which strong reciprocity is selected for in a spatially structured population and highlight that the forces behind its evolution involves kinship (be it genetic or cultural). PMID- 17853991 TI - Conspecific attraction and shelter selection in gregarious insects. AB - During habitat selection, the presence of conspecifics can frequently drive a nonuniform distribution of animals across habitats of equivalent quality. In group-living species, subgroups of individuals might display mutual attraction while differing in their preferences for environmental resources. The final decision to settle requires individuals to integrate both environmental and social cues. This raises the question of the relative importance of sociality and resources preferences in determining habitat choice. In this study, we examined the interactive influence of conspecific attraction on individual resource preferences on refuge choice in groups of cockroaches. Shelters scaled to the sizes of nymphs and adult males were offered to groups of only nymphs and only males and to mixed groups. The choices of males were consistent across social conditions. Conversely, the preferences of nymphs shifted depending on the social context; the presence of males overrode the affinity nymphs had for scaled-size shelters. We developed a numerical model implementing parameters derived from these experiments to test whether the final spatial distribution of individuals originated from a differential attraction between nymphs and males that was associated with their relative body size. Finally, we propose a general framework for understanding how similar mechanisms can promote the skewed distribution of organisms at different spatial scales. PMID- 17853990 TI - Variation in endocrine signaling underlies variation in social life history. AB - Variation in endocrine pathways can be a major mechanism underlying life-history evolution. Yet it is unclear whether this insight, derived primarily from solitary species, explains the origins of complex life-history traits in highly social taxa. Thus, we here document and study variation in social life-history syndromes of female fecundity, behavior, and life span in selectively bred honeybee (Apis mellifera) strains. Associated variation in endocrine signaling was uncovered by RNA interference (RNAi) silencing of the juvenile hormone (JH) suppressor gene vitellogenin. High versus low endocrine reactivity in response to vitellogenin knockdown consistently correlated with rapid social behavioral ontogeny and short life span versus slow social behavioral ontogeny and long life span. Variation in JH reactivity, furthermore, was a function of variation in fecundity (ovary size and follicle development). A JH-mediated pleiotropy of female life-history traits, including fecundity, behavior, and life span, characterizes the distantly related solitary insect Drosophila. For the first time, we document a similar regulatory principle in a highly social species where most females are alloparental helpers (workers) that seldom reproduce. We conclude that variation in endocrine pathways of solitary origin can underlie variation and evolvability of complex social life-history traits. PMID- 17853992 TI - The evolution of dispersal in reserve networks. AB - The fragmentation of an environment into developed and protected areas may influence selection pressure on dispersal by increasing the chance of moving from a favorable to an unfavorable habitat. We theoretically explore this possibility through two cases: (1) marine systems in which reduced predation and/or increased feeding drive the evolution of planktonic larval duration and (2) more generally, where stochasticity in reproductive yield drives the evolution of the proportion of offspring dispersing. Model results indicate that habitat fragmentation generally shifts selection pressure toward reduced dispersal, particularly when areas outside reserves are uninhabitable. However, shifts to increased dispersal may occur when temporal heterogeneity is the primary selective force and constant quota harvest occurs outside reserves. In addition, model results suggest the potential for changes in the genetic variability in dispersal after habitat fragmentation. The predicted evolutionary changes in dispersal will depend on factors such as the relative genetic and environmental contributions to dispersal related traits and the extent of anthropogenic impacts outside reserves. If the predicted evolutionary changes are biologically attainable, they may suggest altering current guidelines for the appropriate size and spacing of marine reserves necessary to achieve conservation and fisheries goals. PMID- 17853993 TI - Trade-offs between the reproductive and immune systems: facultative responses to resources or obligate responses to reproduction? AB - A major challenge in biology is understanding how organisms partition limited resources among physiological processes. For example, offspring production and self-maintenance are important for fitness and survival, yet these critical processes often compete for resources. While physiological trade-offs between reproduction and immune function have been documented, their regulation remains unclear. Most current evidence suggests that physiological changes during specific reproductive states directly suppress various components of the immune system; however, some studies have not found this clear relationship. We performed two experiments in female tree lizards (Urosaurus ornatus) that demonstrate the presence of trade-offs between the reproductive and immune systems under controlled laboratory conditions. These results also support the hypothesis that these trade-offs are a facultative response to resource availability and are not obligatory responses to physiological changes during reproduction. We found that (1) experimentally increasing reproductive investment under limited resources resulted in suppressed immune function and (2) experimentally limiting resources resulted in immunosuppression but only during resource costly reproductive activities. There seems to be a critical balance of resources that is maintained between multiple processes, and changes in the balance between energy intake and output can have major consequences for immune function. PMID- 17853994 TI - Trade-offs between force and fit: extreme morphologies associated with feeding behavior in carabid beetles. AB - We explored how functional trade-offs in resource handling strategies are associated with the divergent morphology of predators. The malacophagous carabid Damaster blaptoides shows two extreme morphologies in the forebody; there is an elongate small-headed type and a stout large-headed type. A feeding experiment showed that the small-headed type obtained a high feeding performance on snails with a thick shell and a large aperture by penetrating the shell with its head. In contrast, the large-headed type showed a high feeding performance on snails that had a thin shell and a small aperture, and they ate these prey by crushing the shell. The large-headed, strong-jawed beetles are efficient at shell crushing but are ineffective at shell entry; the large mandibles and musculature that allow for shell crushing make the beetle's head too wide to penetrate shell apertures. On the other hand, small-headed, weak-jawed beetles crush poorly but can reach into shells for direct predation on snail bodies. These findings are hypothesized to be functional trade-offs between force and fit due to morphological constraints. This trade-off would be a primary mechanism affecting both resource handling ability in animals and phenotypic diversity in predators and prey. PMID- 17853995 TI - Selective predation on wing morphology in sympatric damselflies. AB - Although predation is thought to affect species divergence, the effects of predator-mediated natural selection on species divergence and in nonadaptive radiations have seldom been studied. Wing melanization in Calopteryx damselflies has important functions in sexual selection and interspecific interactions and in species recognition. The genus Calopteryx and other damselfly genera have also been put forward as examples of radiations driven by sexual selection. We show that avian predation strongly affects natural selection on wing morphology and male wing melanization in two congeneric and sympatric species of this genus (Calopteryx splendens and Calopteryx virgo). Predation risk was almost three times higher for C. virgo, which has an exaggerated degree of wing melanization, than it was for the less exaggerated, sympatric congener C. splendens. Selective predation on the exaggerated species C. virgo favored a reduction and redistribution of the wing melanin patch. There was evidence for nonlinear selection involving wing patch size, wing patch darkness, and wing length and width in C. splendens but weaker nonlinear selection on the same trait combinations in C. virgo. Selective predation could interfere with species divergence by sexual selection and may thus indirectly affect male interspecific interactions, reproductive isolation, and species coexistence in this genus. PMID- 17853996 TI - The interactive effects of herbivory and mixed mating for the population dynamics of Impatiens capensis. AB - In this study, we examine the demographic consequences of mixed mating and explore the interactive effects of vegetative herbivory and mating system for population dynamics of Impatiens capensis, a species with an obligate mixed mating system (i.e., individuals produce both obligately selfing cleistogamous and facultatively outcrossing chasmogamous flowers). In two natural populations, we followed seeds derived from cleistogamous and chasmogamous flowers subject to different herbivory levels throughout their life cycle. Using a mating system explicit projection matrix model, we found that mating system types differed in important vital rates. Cleistogamous individuals had higher rates of germination than did chasmogamous individuals, whereas chasmogamous individuals expressed a fecundity advantage over cleistogamous individuals. In addition, population growth was most sensitive to changes in vital rates of cleistogamous individuals, indicating the demographic importance of selfing for these populations. Herbivory also had demographic consequences; a 33%-49% reduction in herbivory caused the population growth rates to increase by 104%-132%, primarily because of effects on vital rates of selfed individuals. Our results not only uncover a novel consequence of mating system expression, that is, mating system influences population dynamics, but also shed light on the role of herbivores in maintaining mixed mating. PMID- 17853997 TI - Are plant populations seed limited? A critique and meta-analysis of seed addition experiments. AB - We examine the relative importance of processes that underlie plant population abundance and distribution. Two opposing views dominate the field. One posits that the ability to establish at a site is determined by the availability of suitable microsites (establishment limitation), while the second asserts that recruitment is limited by the availability of seeds (seed limitation). An underlying problem is that establishment and seed limitation are typically viewed as mutually exclusive. We conducted a meta-analysis of seed addition experiments to assess the relative strength of establishment and seed limitation to seedling recruitment. We asked (1) To what degree are populations seed and establishment limited? (2) Under what conditions (e.g., habitats and life-history traits) are species more or less limited by each? (3) How can seed addition studies be better designed to enhance our understanding of plant recruitment? We found that, in keeping with previous studies, most species are seed limited. However, the effects of seed addition are typically small, and most added seeds fail to recruit to the seedling stage. As a result, establishment limitation is stronger than seed limitation. Seed limitation was greater for large-seeded species, species in disturbed microsites, and species with relatively short-lived seed banks. Most seed addition experiments cannot assess the relationship between number of seeds added and number of subsequent recruits. This shortcoming can be overcome by increasing the number and range of seed addition treatments. PMID- 17853998 TI - Predation and disturbance interact to shape prey species diversity. AB - Though predation, productivity (nutrient richness), spatial heterogeneity, and disturbance regimes are known to influence species diversity, interactions between these factors remain largely unknown. Predation has been shown to interact with productivity and with spatial heterogeneity, but few experimental studies have focused on how predation and disturbance interact to influence prey diversity. We used theory and experiments to investigate how these factors influence diversification of Pseudomonas fluorescens by manipulating both predation (presence or absence of Bdellovibrio bacteriovorus) and disturbance (frequency and intensity of disturbance). Our results show that in a homogeneous environment, predation is essential to promote prey species diversity. However, in most but not all treatments, elevated diversity was transitory, implying that the effect of predation on diversity was strongly influenced by disturbance. Both our experimental and theoretical results suggest that disturbance interacts with predation by modifying the interplay of resource and apparent competition among prey. PMID- 17853999 TI - Temporal but not spatial environmental variation drives adaptive offspring sex allocation in a plural cooperative breeder. AB - Cooperatively breeding birds have been used frequently to study sex allocation because the adaptive value of the sexes partly depends upon the costs and benefits for parents of receiving help. I examined patterns of directional sex allocation in relation to maternal condition (Trivers-Willard hypothesis), territory quality (helper competition hypothesis), and the number of available helpers (helper repayment hypothesis) in the superb starling, Lamprotornis superbus, a plural cooperative breeder with helpers of both sexes. Superb starlings biased their offspring sex ratio in relation to prebreeding rainfall, which was correlated with maternal condition. Mothers produced relatively more female offspring in wetter years, when they were in better condition, and more male offspring in drier years, when they were in poorer condition. There was no relationship between offspring sex ratio and territory quality or the number of available helpers. Although helping was male biased, females had a greater variance in reproductive success than males. These results are consistent with the Trivers-Willard hypothesis and suggest that although females in most cooperatively breeding species make sex allocation decisions to increase their future direct reproductive success, female superb starlings appear to base this decision on their current body condition to increase their own inclusive fitness. PMID- 17854000 TI - Are dietary AGEs/ALEs a risk to human health and, if so, what is the mechanism of action? PMID- 17854001 TI - The health risks of dietary advanced glycation end-products. Interview by Monika Pischetsrieder. PMID- 17854002 TI - Dietary advanced glycation end products--a risk to human health? A call for an interdisciplinary debate. AB - Physiological consequences resulting from protein-bound Maillard compounds in foods must be discussed carefully. This was the idea behind the debate, which is put for discussion by the papers by Sebekova and Somoza, who argued for the motion that dietary advanced glycation end products (AGEs) are a health risk, and by Ames, who provided evidence against the motion. In this two excellent reviews, numerous arguments based on papers published in high-impact journals are given for each of the opinions. The fact that no final conclusion can be drawn, may reflect the need for a more comprehensive examination of this issue in the future. For a deeper understanding of biological consequences resulting from heated foods, the relationships between well-defined biological effects and well characterized chemical structures must be studied. Prerequisite for this is profound chemistry--pure compounds, exact concentrations, and unambiguous analytical techniques. A real "risk assessment" is much too complex than to leave it up to one discipline alone. It must be a comprehensive and interdisciplinary approach, joining the resources of biology, medicine, and chemistry. PMID- 17854003 TI - Dietary advanced glycation endproducts (AGEs) and their health effects--PRO. AB - Thermal processing of food results in the formation of various novel compounds, among others advanced glycation endproducts (AGEs). AGEs result from nonenzymatic glycation reactions between reducing sugars and free amino groups of proteins, peptides, or amino acids. Due to their potential noxious effects, alimentary AGEs are also called glycotoxins. This review provides a summary of the available evidence on the health effects of exaggerated intake of thermally treated food. Data from experimental studies in rodents and from clinical studies in healthy volunteers and in patients suffering from selected diseases in which AGEs are of pathogenetic importance (diabetes, chronic renal failure) are summarized. It is concluded that, an exaggerated intake of thermally processed foods may exert in vivo diabetogenic and nephrotoxic effects, induce low-grade inflammation, enhance oxidative stress, and promote atherosclerosis. PMID- 17854004 TI - Evidence against dietary advanced glycation endproducts being a risk to human health. AB - In vivo, advanced glycation endproducts (AGEs) are linked to various diseases, particularly those associated with diabetes. AGEs are also formed when many foods are thermally processed. The extent to which dietary AGEs are absorbed by the gastrointestinal (GI) tract and their possible role in the onset and promotion of disease are currently of considerable interest. This paper reviews information that supports the argument that dietary AGEs are not a risk to human health. PMID- 17854005 TI - Dietary advanced lipoxidation products as risk factors for human health--a call for data. PMID- 17854006 TI - Dietary advanced lipid oxidation endproducts are risk factors to human health. AB - Lipid oxidation in foods is one of the major degradative processes responsible for losses in food quality. The oxidation of unsaturated fatty acids results in significant generation of dietary advanced lipid oxidation endproducts (ALEs) which are in part cytotoxic and genotoxic compounds. The gastrointestinal tract is constantly exposed to dietary oxidized food compounds, after digestion a part of them are absorbed into the lymph or directly into the blood stream. After ingestion of oxidized fats animals and human have been shown to excrete in urine increase amounts of malondialdehyde but also lipophilic carbonyl compounds. Oxidized cholesterol in the diet was found to be a source of oxidized lipoproteins in human serum. Some of the dietary ALEs, which are absorbed from the gut to the circulatory system, seems to act as injurious chemicals that activate an inflammatory response which affects not only circulatory system but also organs such as liver, kidney, lung, and the gut itself. We believe that repeated consumption of oxidized fat in the diet poses a chronic threat to human health. High concentration of dietary antioxidants could prevent lipid oxidation and ALEs generation not only in foods but also in stomach condition and thereby potentially decrease absorption of ALEs from the gut. This could explains the health benefit of diets containing large amounts of dietary antioxidants such those present in fruits and vegetables, or products such as red-wine or tea consuming during the meal. PMID- 17854007 TI - Dietary ALEs are a risk to human health--NOT! AB - Advanced lipoxidation end-products (ALEs) are formed by reaction of protein with lipid-derived reactive peroxyl and carbonyl compounds produced during food processing and cooking. There is concern that ALEs may induce damage in the gastrointestinal tract, affecting gut health, or enter the body and promote vascular inflammation and tissue damage. However, there is no direct evidence that ALE-proteins are a source of damage in the intestines or that they are transported into the circulation and cause pathology. Modification of proteins by ALEs impedes their digestion, and reactive ALEs released by gastrointestinal proteases would react with proteins or peptides in the gut, limiting their absorption. There are also potent enzymatic mechanisms for detoxifying ALEs or their precursors prior to their entry into the circulation. If ALEs gain access to the circulation, a battery of protective enzymes in tissue provides a second level of defense. These enzymes may be induced in intestinal epithelia and liver by low doses of ALEs, and adaptive responses would provide enhanced protection against future exposure to ALEs. Overall, except in persons with compromised organ function, e. g., vascular, hepatic, or renal diseases, there is little evidence that food ALEs will have any significant pathological effects. PMID- 17854008 TI - Dietary AGEs and ALEs and risk to human health by their interaction with the receptor for advanced glycation endproducts (RAGE)--an introduction. AB - The receptor for advanced glycation endproducts (RAGE) has a well-substantiated role in cell dysfunction and mechanisms of inflammatory disease. The physiological agonists of RAGE are less certain: S100/calgranulin proteins, high mobility group-1 protein HMGB1 and other proteins are candidate agonists. It increasingly appears unlikely proteins modified by advanced glycation endproducts are effective agonists in vivo. In the following debate, Professors Ann Marie Schmidt and Claus Heizmann gave arguments and evidences for and against the motion. Recent evidence suggesting the activation of RAGE impairs the enzymatic defence against glycation provided by glyoxalase 1 (Glo 1) suggests that studies of RAGE will continue to be of importance to our understanding of the physiological significance of protein glycation. PMID- 17854009 TI - Arguing for the motion: yes, RAGE is a receptor for advanced glycation endproducts. AB - Advanced glycation endproducts (AGEs) are an heterogenous class of compounds formed by diverse stimuli, including hyperglycemia, oxidative stress, inflammation, renal failure, and innate aging. Recent evidence suggests that dietary sources of AGE may contribute to pathology. AGEs impart diverse effects in cells; evidence strongly suggests that crosslinking of proteins by AGEs may irrevocably alter basement membrane integrity and function. In addition, the ability of AGEs to bind to cells and activate signal transduction, thereby affecting broad properties in the cellular milieu, indicates that AGEs are not innocent bystanders in the diseases of AGEing. Here, we present evidence that receptor for AGE (RAGE) is a receptor for AGEs. PMID- 17854011 TI - The mechanism by which dietary AGEs are a risk to human health is via their interaction with RAGE: arguing against the motion. AB - We are interested in the regulation of intracellular calcium and the various diseases associated with an altered regulation of this second messenger. More recently, we also became interested in pathologies involving the Ca2+-binding S100 proteins and AGEs and their association with the multifunctional Receptor for Advanced Glycation Endproducts (RAGE). PMID- 17854012 TI - Mesoporous materials for drug delivery. AB - Research on mesoporous materials for biomedical purposes has experienced an outstanding increase during recent years. Since 2001, when MCM-41 was first proposed as drug-delivery system, silica-based materials, such as SBA-15 or MCM 48, and some metal-organic frameworks have been discussed as drug carriers and controlled-release systems. Mesoporous materials are intended for both systemic delivery systems and implantable local-delivery devices. The latter application provides very promising possibilities in the field of bone-tissue repair because of the excellent behavior of these materials as bioceramics. This Minireview deals with the advances in this field by the control of the textural parameters, surface functionalization, and the synthesis of sophisticated stimuli-response systems. PMID- 17854013 TI - From amino acids to heteroaromatics--thiopeptide antibiotics, nature's heterocyclic peptides. AB - Amino acids, the building blocks of proteins, also serve as precursors to a wide range of other naturally occurring substances including alkaloids, antibiotics, and, the subject of this Review, heterocyclic peptides. Simple alpha-amino acids are converted into complex arrays of heteroaromatic rings that display interesting and potent biological activity. The thiopeptide antibiotics, with their complex molecular architectures, are wonderful examples. In this Review we show how organic chemists have developed innovative methods for the synthesis of the heterocyclic ring systems, including routes inspired by the likely biosynthetic processes, and successfully assembled such building blocks into the final target molecule by application of orthogonal protecting groups and coupling methodologies. PMID- 17854014 TI - Deactivation of ruthenium olefin metathesis catalysts through intramolecular carbene-arene bond formation. PMID- 17854015 TI - Simultaneous nucleotide activation and synthesis of amino acid amides by a potentially prebiotic multi-component reaction. PMID- 17854016 TI - Creating a reactive enediyne by using visible light: photocontrol of the Bergman cyclization. PMID- 17854017 TI - Lecithin-based water-in-oil compartments as dividing bioreactors. AB - Like liposomes, water-in-oil (w/o) emulsions have recently been used as bioreactors, since they permit facile compartmentation, and therefore the creation of a synthetic cell-like structure. We show here for the first time that lecithin-based w/o compartments can also be used for these purposes and in particular as compartments for hosting complex biochemical reactions that lead to protein synthesis. The expression of enhanced green fluorescent protein (EGFP), used as a model reaction, was followed by fluorescence microscopy. EGFP was synthesised inside the bioreactors either through simultaneous incorporation of all components for transcription and translation reactions in a single emulsion, or through the mixing of four different emulsions, each containing only part of the molecular machinery. Mechanical energy (i.e., stirring) must be provided to the system in order to force solute exchange and/or fusion processes between droplets. Finally, we demonstrate that, in the presence of excess lecithin, preformed w/o compartments can undergo spontaneous division, reducing the average droplet size, increasing the number of droplets, and continuing the protein expression after the division. We briefly comment on how this type of work extends and links the previously reported work on self-reproduction in vesicles, micelles and reverse-micelles. PMID- 17854018 TI - Dynamic conformational behavior and molecular interaction discrimination of DNA/binder complexes by single-chain stretching in a microdevice. PMID- 17854019 TI - Interactive transport of guanidinylated poly(propylene imine)-based dendrimers through liposomal and cellular membranes. AB - The ability of guanidinylated poly(propylene imine) dendrimers to translocate across lipid bilayers was assessed by employing either a model phosphate-bearing liposomal membrane system or A549 human lung carcinoma cells. Two dendrimer generations, differing in the number of surface guanidinium groups, were employed, while surface acetylation or the use of spacers affected the binding of the guanidinium group to the phosphate moiety and finally the transport efficiency. Following adhesion of dendrimers with liposomes, fusion or transport occurred. Transport through the liposomal bilayer was observed at low guanidinium/phosphate molar ratios, and was enhanced when the bilayer was in the liquid-crystalline phase. For effective transport through the liposomal membrane, an optimum balance between the binding strength and the degree of hydrophobicity of the guanidinylated dendrimer is required. In experiments performed in vitro with cells, efficient penetration and internalization in subcellular organelles and cytosol was observed. PMID- 17854020 TI - Antiplasmodial and prehemolytic activities of alpha-peptide-beta-peptoid chimeras. PMID- 17854021 TI - Transfer printing of DNA by "click" chemistry. AB - This paper describes a straightforward procedure to immobilize oligonucleotides on glass substrates in well-defined micropatterns by microcontact printing with a dendrimer-modified stamp. The oligonucleotides are efficiently immobilized by "click" chemistry induced by microcontact printing. Acetylene-modified oligonucleotides were treated with an azide-terminated glass slide under the confinement of the dendrimer-modified stamp, without the use of a Cu(I) catalyst. The immobilization is an irreversible, covalent, and one-step reaction that results in stable attachment of the oligonucleotides. Oligonucleotides with the acetylene-modification at the 5' terminus hybridize selectively with full-length, complementary targets. Strands with more than one acetylene linker do not hybridize with complementary strands. PMID- 17854022 TI - Novel inhibitors of checkpoint kinase 1. PMID- 17854023 TI - Mapping of the cerebral vascular response to hypoxia and hypercapnia using quantitative perfusion MRI at 3 T. AB - Changes in breathing change the concentration of oxygen and carbon dioxide in arterial blood resulting in changes in cerebral blood flow (CBF). This mechanism can be described by the cerebral vascular response (CVR), which has been shown to be altered in different physiological and pathophysiological states. CBF maps of grey matter (GM) were determined with a pulsed arterial spin labelling technique at 3 T in a group of 19 subjects under baseline conditions, hypoxia, and hypercapnia. Experimental conditions allowed a change in either arterial oxygen (hypoxia) or carbon dioxide (hypercapnia) concentration compared with the baseline, leaving the other variable constant, in order to separate the effects of these two variables. From these results, maps were calculated showing the regional distribution of the CVR to hypoxia and hypercapnia in GM. Maps of CVR to hypoxia showed very high intra-subject variations, with some GM regions exhibiting a positive response and others a negative response. Per 10% decrease in arterial oxygen saturation, there was a statistically significant 7.0 +/- 2.9% (mean +/- SEM) increase in GM-CBF for the group. However, 70% of subjects showed an overall positive CVR (positive responders), and the remaining 30% an overall negative CVR (negative responders). Maps of CVR to hypercapnia showed less intra subject variation. Per 1 mm Hg increase in partial pressure of end-tidal carbon dioxide, there was a statistically significant 5.8 +/- 0.9% increase in GM-CBF, all subjects showing an overall positive CVR. As the brain is particularly vulnerable to hypoxia, a condition associated with cardiorespiratory diseases, CVR maps may help in the clinic to identify the areas most prone to damage because of a reduced CVR. PMID- 17854024 TI - Activities of human papillomavirus 16 E6 natural variants in human keratinocytes. AB - Genetic variations in the E6 oncogene have been associated with different risk for cancer progression. In the present study, the functional significance of human papillomavirus (HPV) polymorphism in the E6 oncogene was investigated. Ten HPV16 E6 variants containing amino acid substitutions in the N-terminal region of E6 were evaluated for different biological and biochemical activities in human keratinocytes, the target cells for HPV infection. Western blot analyses of primary foreskin human keratinocytes or immortalized human keratinocytes, stably transduced with the E6 variants, revealed reduced p53 and Bax levels in all E6 expressing cultures. The reduction induced by most E6 proteins was at similar levels and comparable to the reduction induced by the E6 prototype. The ability of the proteins to induce serum/calcium-differentiation resistant colonies in primary keratinocytes was more variable. Overall activities of the variants ranged between 0.24- and 2.18-fold of the E6 prototype activity. The I27R/L83V variant showed the lowest activity whereas the R8Q variant showed the highest activity. The L83V polymorphism previously associated with risk for cancer progression in some populations, showed significant activity, comparable to that of the E6 prototype, in reducing p53 and Bax levels. Furthermore, this variant showed enhancement in the ability to induce colonies resistant to serum/calcium triggered differentiation, however, the difference from the prototype was not statistically significant. This, and augmentation of other described functions might result in differences in L83V pathogenicity. PMID- 17854025 TI - Real-time PCR and its application to mumps rapid diagnosis. AB - A real-time polymerase chain reaction assay was initially developed in China to detect mumps genome. The primers and TaqMan-MGB probe were selected from regions of the hemagglutinin gene of mumps virus. The primers and probe for the real-time PCR were evaluated by both laboratories in China and in the UK using three different pieces of equipment, LightCycler (Roche), MJ DNA Engine Option 2 (BIO RAD) and TaqMan (ABI Prism) on different samples. The reaction was performed with either a one-step (China) or two-step (UK) process. The sensitivity (10 copies) was estimated using a serial dilution of constructed mumps-plasmid DNA and a linear standard curve was obtained between 10 and 10(7) DNA copies/reaction, which can be used to quantify viral loads. The detection limit on cell culture grown virus was approximately 2 pfu/ml with a two-step assay on TaqMan, which was equivalent to the sensitivity of the nested PCR routinely used in the UK. The specificity was proved by testing a range of respiratory viruses and several genotypes of mumps strains. The concentration of primers and probe is 22 pmol and 6.25 or 7 pmol respectively for a 25 microl reaction. The assay took 3 hr from viral RNA extraction to complete the detection using any of the three pieces of equipment. Three hundred forty-one (35 in China and 306 in the UK) clinical specimens were tested, the results showing that this real-time PCR assay is suitable for rapid and accurate detection of mumps virus RNA in various types of clinical specimens. PMID- 17854026 TI - Virological and clinical aspects of HBV-HCV coinfection in HIV positive patients. AB - In a long-term follow-up study the clinical and virological presentation of HBV/HCV coinfection in anti-HIV positive patients was evaluated. Plasma HBV-DNA, HCV-RNA, and HIV-RNA were determined by PCR in 5 HBsAg/anti-HCV/anti-HIV positive patients, in 4 HBsAg/anti-HIV positive patients and in 82 anti-HCV/anti-HIV positive patients first observed at a Unit of Infectious Diseases in Naples (Italy) from 1990 to 2000 (follow up 6-16 years). All five hepatitis B and C coinfected patients showed reciprocal inhibition of viral replication on admission and during the follow up. At the end of the follow up a clearance of HBsAg from serum was observed in four patients and a clearance of anti-HCV in one of them. In two patients after clearance of HBsAg, evidence of occult HBV infection was observed, at times associated with a hepatic flare. None of the four patients with HIV/HBV coinfection lost HBsAg and none of the 82 with HIV/HCV coinfection lost anti-HCV during the follow up. In anti-HIV positive patients HBV/HCV coinfection is characterized by reciprocal inhibition of viral replication, more evident in HBV expression in plasma and at times by progression to occult HBV infection. PMID- 17854027 TI - Mutational patterns and correlated amino acid substitutions in the HIV-1 protease after virological failure to nelfinavir- and lopinavir/ritonavir-based treatments. AB - Human immunodeficiency virus type 1 (HIV-1) antiviral drug resistance is a major consequence of therapy failure and compromises future therapeutic options. Nelfinavir and lopinavir/ritonavir-based therapies have been widely used in the treatment of HIV-infected patients, in combination with reverse transcriptase inhibitors. The aim of this observational study was the identification and characterization of mutations or combinations of mutations associated with resistance to nelfinavir and lopinavir/ritonavir in treated patients. Nucleotide sequences of 1,515 subtype B HIV-1 isolates from 1,313 persons with different treatment histories (including naive and treated patients) were collected in 31 Spanish hospitals over the years 2002-2005. Chi-square contingency tests were performed to detect mutations associated with failure to protease inhibitor-based therapies, and correlated mutations were identified using statistical methods. Virological failure to nelfinavir was associated with two different mutational pathways. D30N and N88D appeared mostly in patients without previous exposure to protease inhibitors, while K20T was identified as a secondary resistance mutation in those patients. On the other hand, L90M together with L10I, I54V, A71V, G73S, and V82A were selected in protease inhibitor-experienced patients. A series of correlated mutations including L10I, M46I, I54V, A71V, G73S, and L90M appeared as a common cluster of amino acid substitutions, associated with failure to lopinavir/ritonavir-based treatments. Despite the relatively high genetic barrier of some protease inhibitors, a relatively small cluster of mutations, previously selected under drug pressure, can seriously compromise the efficiency of nelfinavir- and lopinavir/ritonavir-based therapies. PMID- 17854028 TI - Favorable outcome of ex-vivo purging of monocytes after the reintroduction of treatment after interruption in patients infected with multidrug resistant HIV-1. AB - In multidrug resistant patients treatment interruptions allow the selection of archived wild-type drug-susceptible viruses that compete for the less fit drug resistant strains. However, the selection of viruses with increased replicative capacity is often followed by a loss of CD4+ T cells. In addition, drug resistant variants later re-emerge limiting the overall clinical benefit of treatment interruption. Blood monocytes are a key component of the HIV reservoir and can be partially removed by a system for purging of myeloid cells (MYP). This study tested the safety and efficacy of MYP on multidrug resistant patients who underwent treatment interruption. Twelve patients were randomized to receive or not six cycles of MYP during treatment interruption. An optimized antiretroviral regimen was reintroduced after the reappearance of a drug susceptible genotype. Following therapy reintroduction, a long lasting increase in CD4+ T cell counts was observed only in the treatment interruption + MYP patients but not in the control patients. Five/six treatment interruption + MYP patients never experienced virological rebound during a median follow up period of 98 weeks. In contrast, 4/6 patients who did not receive MYP never reached complete viral suppression and had a virological rebound after a median of 16.5 weeks after treatment reintroduction. The difference between the two groups in the time to virological rebound was statistically significant (P = 0.021). A consistent decrease of HIV DNA load in CD14+ purified cells was observed only in treatment interruption + MYP patients. These data suggest that MYP can improve the immunological and virological response to treatment interruption. PMID- 17854029 TI - Influence of specific muscle training on pain, activity limitation and kinesiophobia in women with back pain post-partum--a 'single-subject research design'. AB - BACKGROUND AND PURPOSE: Many women suffer from back pain and experience activity limitation post-partum. To our knowledge the physiological factors and physiotherapy related to back pain post-partum have received limited evaluation and the effectiveness of specific physiotherapeutic approaches to exercise should be tested. In addition, there has been limited research on kinesiophobia in women with back pain post-partum. The purpose of the current study was to test the influence of specific trunk muscle training on pain, activity limitation and kinesiophobia in 10 subjects with back pain post-partum. METHOD: The treatment consisted of specific deep muscle training of the transversus abdominus and multifidus muscles. Pain was rated based on the visual analogue scale (VAS) and pain drawings. Activity limitation was recorded using the Disability Rating Index. Kinesiophobia was evaluated using the Swedish version of the Tampa Scale for Kinesiophobia. An A-B-A single-subject research design was used and a number of measurements were obtained during each phase. The analysis consisted of a visual inspection and a two standard deviation band test (2-SD). RESULTS: The visual analysis showed a trend towards reduced pain and activity limitation for all 10 subjects. The 2-SD test showed mixed results among all subjects. In addition, all subjects reported kinesiophobia before and after treatment. CONCLUSIONS: Individual specific deep muscle training of the transversus abdominus and multifidus muscles reduced pain and activity limitation in women with back pain post-partum. Further research is needed to determine more precisely how kinesiophobia affects women with back pain post-partum. PMID- 17854030 TI - Redetection of HBV lamivudine-resistant mutations in a patient under entecavir therapy, who had been treated sequentially with nucleos(t)ide analogues. AB - Development of hepatitis B virus (HBV)-resistant strains following nucleos(t)ide analog treatment is a major medical concern. This report describes a case of an adult patient with chronic HBV infection, sequentially treated with the nucleos(t)ide analogues, lamivudine, adefovir, and entecavir. During monotherapy with lamivudine, the patient developed lamivudine-resistant variants, which were undetectable during adefovir dipivoxil monotherapy. Twenty-two months after discontinuing lamivudine therapy, the resistant variants were again detected while the patient was receiving entecavir monotherapy. Genotypic analysis by sequencing the HBV polymerase was confirmed with the INNO-LiPA method. The results of this study suggest that entecavir treatment reselected residual lamivudine-resistant HBV variants, possibly because lamivudine-resistant HBV is less susceptible to entecavir than the wild-type virus. Despite the presence of these variants, the patient has had a complete virological response. PMID- 17854031 TI - Characterization of hepatitis E virus from outbreak and sporadic cases in Turkmenistan. AB - Large outbreaks and sporadic cases of hepatitis E have been reported in Central Asia. We assessed the genetic relatedness of hepatitis E virus (HEV) strains from outbreak and sporadic cases in Turkmenistan. Specimens from outbreak and sporadic cases of acute hepatitis non-A, non-B were tested by reverse transcription (RT) polymerase chain reaction (PCR) to identify the presence of HEV RNA; nucleotide sequences were analyzed. HEV RNA was detected from 23/156 (15%) outbreak cases and 2/23 (9%) sporadic cases. The HEV outbreak isolates represented 14 unique sequences with genetic distances varying between 0.3% and 8.6%, 12 of which were closely related, with distances between 0.3% and 5.6%. Two unique sequences from outbreak cases 32 and 42 were closely related (99.7%) and shared 91.8-93.4% of sequence with the other 12 strains. The two strains were closely related to the previously published isolates from Burma (99.7-100%) and India-Madras (95.7 96.1%). The two 1994 sporadic HEV strains were 97.4% distinct, wile revealing 91.4-94.1% homology to 1985 strains, and 94.4-94.7% to HEV from the neighboring China and Pakistan. Genetic diversity of HEV that caused the hepatitis E outbreak in Turkmenistan in 1985 suggests heterogeneity of viral sources. Sporadic hepatitis E that occurred in 1994 was caused by viral strains genetically distinct from those causing the outbreak in 1985, yet closely related to HEV from neighboring countries. The study suggests that circulation of a broad variety of strains of HEV may occur in Central Asia, regardless of international borders, presenting a significant public health threat to the population of the region. PMID- 17854032 TI - Changing pattern of rotavirus G genotype distribution in Chiang Mai, Thailand from 2002 to 2004: decline of G9 and reemergence of G1 and G2. AB - Group A rotaviruses are the most common cause of acute viral diarrhea in humans and animals throughout the world. Previous surveillance studies of group A rotaviruses in Thailand indicated that the dominant types of rotaviruses were changing from time to time. During 2000 and 2001, the G9 rotavirus emerged as the most prevalent genotype, with an exceptionally high frequency (91.6%) in Chiang Mai, Thailand. In the year 2002-2004, group A rotavirus was detected in 98 out of 263 (37.3%) fecal specimens collected from children hospitalized with diarrhea. Of these, 40 (40.8%) were G9P[8], 33 (33.7%) were G1P[8], 23 (23.5%) were G2P[4], and 2 (2.0%) were G3P[9]. The G9P[8] was found to be the most predominant strain in 2002, but the prevalence rate abruptly decreased during the period 2003-2004. In addition, G2P[4] reemerged in the epidemic season of 2003, whereas G1P[8] became the most predominant strain in the following year (2004). Phylogenetic analysis of the VP7 genes revealed that G1, G2, and G9 rotavirus strains clustered together with recently circulating strains, which were isolated from different regional settings in Thailand. In conclusion, the study demonstrated a decrease of incidence of G9P[8] and reemergence of G1P[8] and G2P[4] rotaviruses in Chiang Mai, Thailand during the period 2002-2004. These data imply that the distribution of group A rotavirus genotypes circulating in Chiang Mai, Thailand, changes over time. PMID- 17854033 TI - Microarray analyses of differentially expressed human genes and biological processes in ECV304 cells infected with rubella virus. AB - Changes in mRNA expression levels of ECV304 cells infected with the wild-type rubella strain were analyzed using a microarray system representing 18,716 human genes. Four hundred eighty-seven genes exhibited differential expression levels; 456 of these genes were up-regulated while 31 genes were down-regulated. We identified 53 biological processes that were significantly relevant to the RV infection. Among these biological processes, 52 were one-gene processes and one was a process involving five genes: IFNA21 (interferon, alpha 21), interferon stimulated exonuclease gene 20 kDa (ISG20), zinc finger protein 175 (ZNF175), tripartite motif-containing 22 (TRIM22), and MX2 [myxovirus (influenza virus) resistance 2 (mouse)]. Except for ZNF175, gene annotation indicated four of these genes encoded interferon or interferon-induced genes. These results suggest that genes relevant to interferon-regulated pathways may be involved in the pathogenesis of rubella. PMID- 17854034 TI - Mutational patterns of hepatitis B virus genome and clinical outcomes after emergence of drug-resistant variants during lamivudine therapy: analyses of the polymerase gene and full-length sequences. AB - It remains unclear whether mutational patterns of the hepatitis B virus (HBV) genome are associated with the development of severe hepatitis after the emergence of tyrosine-methionine-aspartate-aspartate (YMDD) variants during lamivudine treatment. Thirty patients with chronic hepatitis B who had YMDD variants during lamivudine therapy and were followed up subsequently while receiving lamivudine alone for at least 6 months were examined retrospectively. The lamivudine resistant mutations in the HBV polymerase gene were detected by a line probe assay, and the full-length sequences of HBV DNA were determined in some patients. Between months 5 and 33 of therapy, mutations from methionine to isoleucine at rt204 (rtM204I) were detected in 18 patients, and mutations from methionine to valine at rt204 (rtM204V) were detected in 12. The rtM204V mutations were always accompanied by mutations from leucine to methionine at rt180 (rtL180M), while rtM204I mutations were not. Baseline characteristics, alanine aminotransferase (ALT) levels, and HBV DNA levels within 6 months after the emergence of YMDD variants did not differ significantly between patients with rtM204I alone and those with rtL180M/rtM204V. No specific mutation was identified on full-length sequence analysis in three patients with a hepatitis flare. During long term follow-up, the addition of rtL180M to rtM204I was found in four patients 7-31 months after detecting the change at rt204 and was linked to increased ALT levels. In conclusion, mutational patterns of HBV DNA at the time of emergence of YMDD variants were apparently unrelated to the clinical outcomes in Japanese patients with chronic hepatitis B during lamivudine therapy. PMID- 17854035 TI - Predictors of viral kinetics to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b. AB - For chronic hepatitis C virus (HCV) infection, evaluation of response to peginterferon (PEG-IFN) plus ribavirin (RBV) therapy based on viral kinetics is useful as an early predictor of treatment efficacy, but the underlying mechanisms of the different viral kinetics to treatment are still unclear. The response to 48-week PEG-IFN-RBV combination therapy was evaluated in 160 Japanese adult patients infected with HCV genotype 1b and determined the rapid virological response (at 4 weeks), early virological response (at 12 weeks), end-of treatment response, and sustained virological response (6 months after end of treatment). The proportion of patients who showed rapid, early and sustained virological, and end-of treatment responses were 50%, 73%, 47%, and 71%, respectively. Furthermore, 66% of patients who achieved early virological response also showed sustained virological response. Multivariate analysis identified substitutions of amino acid (aa) 70 and 91 in the HCV core region (double-wild-type) as a predictor of early HCV-RNA negativity, rapid, early, and sustained virological responses and end-of treatment response, and lipid metabolic factors (high levels of LDL cholesterol and total cholesterol) as predictors of early and rapid virological responses and end-of treatment response. Male sex and low levels of alpha-fetoprotein were other predictors of sustained virological response. Furthermore, female sex and severity of liver fibrosis were determinants of lack of sustained virological response in spite of early virological response. This study identified predictors of efficacy of PEG-IFN-RBV therapy based on viral kinetics in Japanese patients infected with HCV genotype 1b. PMID- 17854036 TI - Structural variability of the carboxy-terminus of Epstein-Barr virus encoded latent membrane protein 1 gene in Hodgkin's lymphomas. AB - Epstein-Barr virus (EBV) is implicated in the pathogenesis of several lymphoid and epithelial neoplasms. Latent membrane protein 1 (LMP1) is the major viral oncogene and it is controversial whether tumor LMP1 variants reflect their geographical predominance or are associated with enhanced oncogenic properties. This study aimed to analyze LMP1 molecular variability of 62 EBV+ Hodgkin's lymphomas and 22 non-neoplastic controls from Brazil and Argentina. EBV association was characterized by EBER-ISH, LMP1 immunohistochemistry and PCR assays for EBNA2 and 3C (typing), LMP1 30 bp deletion (del30) and number of 33 bp tandem repeats. LMP1 C-terminal sequencing was performed in 42 cases. EBV1 was the predominant strain in both geographical Hodgkin's lymphoma groups (average 82%). A higher frequency of del30 variant was observed in lymphomas (41/63) than in non-neoplastic controls (6/22) (OR 4.97, CI 95% 1.53-16.79; P = 0.005, chi(2) test). A large number (5-7) of 33 bp repeat units was characteristic of del30 LMP1 variants (P < 0.0001, Fisher's exact test). Sequence analysis showed a similar mutation spectrum to that described worldwide but none of the current classification schemes could be applied completely. A distinct structural pattern was observed in del30 variants, characterized by a large number of 33 bp repeat units and the presence of a 15 bp insertion encoding the JAK3 Box-1a motif (3/15 wt vs. 16/20 del30; P = 0.001, chi(2) test). The results suggest a pathogenic role for LMP1 del30 variants in Hodgkin's lymphoma from South America and point to particular virus-host molecular mechanisms, such as genomic instability in LMP1 carboxy-terminus, leading to enhanced production and selection of these deletion variants. PMID- 17854038 TI - Soochong virus and Amur virus might be the same entities of hantavirus. AB - Amur virus (AMRV) and Soochong virus (SOOV) were reported to be carried by Korean field mice (Apodemus peninsulae) in the Far East of Russia, China, and Korea. The distinction and demarcation between these two viruses have been a matter of debate. In order to clarify this issue and to confirm taxonomic position of AMRV and SOOV, the extensive phylogenetic analyses based on entire S segment and entire M segment sequences of AMRV, SOOV and other reference virus strains deposited in GenBank, were carried out using maximum likelihood and distant matrix methods. All inferred phylogenies revealed that all AMRV strains from China and Far East and SOOV (especially SOO-1/2 strains from Northeastern Korea) shared high identities of nucleotide sequences and were monophyletic distinct from Apodemus agrarius HTNV. Although two genetic sublineages of SOOV exist, these findings revealed that AMRV and SOOV might belong to the same entities of hantavirus. PMID- 17854037 TI - Molecular characterization of G11P[25] and G3P[3] human rotavirus strains associated with asymptomatic infection in South India. AB - Rotaviruses are the major etiological agents of diarrhea in children less than 5 years of age. Two unusual rotavirus strains not previously reported in India, G11P[25] (CRI 10795) and G3P[3] (CRI 33594) were isolated from faecal samples of asymptomatic children in India. The strains were characterized by sequence analysis of the genes encoding the VP7, VP4, VP6, and NSP4. The G11P[25] strain was closely related to the human G11P[25] strains from Bangladesh (with 98% identity at the nucleotide [nt] level and the amino acid [aa] level for the VP7 gene and 96% identity at the nt and 98% at the aa level for the VP4 gene). The G3P[3] strain was found to be related to a G3P[3] strain isolated in Thailand (CMH222; 88% identity at the nt level and 97% at aa level for the VP7 gene and 84% identity at the nt level and 90% at the aa level for the VP4 gene). Phylogenetic analysis of the VP6 and the NSP4 genes revealed that the Vellore G11P[25] strain was of VP6 subgroup II and NSP4 genotype B. The G3P[3] strain was identified as NSP4 genotype C and the VP6 gene showed 97% identity at the deduced amino acid level with strain CMH222 (Thailand) strain but did not cluster with sequences of SGI, SGII, SGI+II or SG-nonI/nonII. Both strains had gene segments of animal rotavirus origin suggesting inter-species transmission of rotavirus, and in the case of G11P[25] possibly underwent reassortment subsequently with human strains resulting in an animal-human hybrid strain. PMID- 17854039 TI - Fifteen years of env C2V3C3 evolution in six individuals infected clonally with human immunodeficiency virus type 1. AB - The study of the evolution of human immunodeficiency virus type 1 (HIV-1) requires blood samples collected longitudinally and data on the approximate time point of infection. Although these requirements were fulfilled in several previous studies, the infectious sources were either unknown or heterogeneous genetically. In the present study, HIV-1 env C2V3C3 (nt 7029-7315) evolution was examined retrospectively in a cohort of hemophiliacs. Compared to other cohorts, the area of interest here was the infection of six hemophiliacs by the same virus strain, that is, the infecting viruses shared an identical genome. As expected, divergence from the founder sequence as well as interpatient divergence of the predominant virus strains increased significantly over time. Based on the V3 nucleotide sequences, CCR5 usage was predicted exclusively throughout the whole period of infection in all patients. Interestingly, common patterns of viral evolution were detected in the patients of the cohort. Four amino acid substitutions within the V3 loop emerged and persisted subsequently in five (positions 305 and 308 of the HXB2 gp120 reference sequence) and six patients (positions 325 and 328 in HXB2 gp120), respectively. These common changes within the V3 loop are likely to be enforced by HIV-1 specific immune response. PMID- 17854040 TI - Mutations associated with lamivudine-resistance in therapy-naive hepatitis B virus (HBV) infected patients with and without HIV co-infection: implications for antiretroviral therapy in HBV and HIV co-infected South African patients. AB - This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-naive HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty five lamivudine-naive HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-naive HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients. PMID- 17854041 TI - High prevalence of occult hepatitis B virus infection in Taiwanese intravenous drug users. AB - The epidemiology and impact of occult HBV infection in intravenous drug users remain largely unknown. The aim of the study was to investigate the prevalence of occult HBV infection among intravenous drug users in Taiwan. Molecular assays were used to determine the level of serum HBV DNA and the genotype in 304 intravenous drug users negative for both HBsAg and anti-HCV. Of 304 intravenous drug users, 125 (41.1%) were positive for serum HBV DNA. The genotype distribution of HBV was as follows: B, 55 (44%); C, 29 (23%); and mixed B and C infections, 41 (33%). The mean and median serum HBV DNA levels in 125 intravenous drug users with occult HBV infection were 4.0 +/- 0.6 and 4.0 log(10) copies/ml, respectively. The mean serum HBV DNA level in carriers with mixed genotype B and C infections was significantly higher than those infected with HBV genotype B or genotype C alone (mean, 4.2 +/- 0.6 log(10) vs. 3.9 +/- 0.5 log(10), and 3.9 +/- 0.7 log(10) copies/ml, P = 0.01 and 0.05, respectively). The amino acid sequence determination of HBV surface gene in 20 intravenous drug users with occult HBV infection selected at random showed no mutation of amino acid at codon 145. In conclusion, the prevalence of occult HBV infection and mixed HBV genotype infections are not uncommon in intravenous drug users residing in an HBV endemic areas. In addition, intravenous drug users with occult mixed genotype B and C infections have significantly higher viral loads than those with occult infection of single HBV genotype. PMID- 17854042 TI - Molecular characterization of calicivirus strains detected in outbreaks of gastroenteritis in Argentina. AB - Eight outbreaks of acute gastroenteritis occurred in Argentina in 2004 were tested for the presence of Calicivirus, Rotavirus and Astrovirus as possible causative agents. Caliciviruses were found in 39 out of the 100 tested samples, followed by six Astrovirus-positive samples and two Rotavirus-positive samples. Thirty-seven out of the 39 Calicivirus-positive samples were typed as Norovirus while the remaining two were typed as Sapovirus. Sequence and phylogenetic analyses of 13 Norovirus-positive samples revealed the presence of strains from the genogroups GI, GII, and GIV. Six Norovirus strains were grouped with the GIV 1 strains, three with the GIIb strains, two with the Farmington Hill-cluster (GII 4) strains, and the remaining two with the GI strains. To our knowledge, this study constitutes the first report of molecular epidemiology of human Caliciviruses associated to gastroenteritis outbreaks in Argentina and the circulation of GIIb and GIV-1 strains in South-America. PMID- 17854043 TI - Native early antigen of Epstein-Barr virus, a promising antigen for diagnosis of nasopharyngeal carcinoma. AB - The Epstein-Barr virus (EBV) early antigen (EA) complex consists of multiple proteins with relevance for diagnosis of acute, chronic and malignant EBV related diseases, including nasopharyngeal carcinoma (NPC). In a recent study, it was found that the molecular diversity of EBV-specific IgG and IgA antibody responses in NPC patients and demonstrated that these reflect independent B-cell triggering leading to distinct EBV antigen-recognition profiles. The fine-specificity of NPC related IgG and IgA responses was explored further against defined recombinant and synthetic EBV-EA antigens using immunofluorescence, immunoblot and ELISA techniques and determined their diagnostic value in a large panel of sera from NPC (n = 154), non-NPC tumor patients (n = 133), acute mononucleosis patients (n = 70) and healthy EBV carriers (n = 259). Individual recombinant EBV-EA markers yielded sensitivity/specificity values not exceeding 86%, whereas selected EA specific peptide epitopes were rather poorly recognized by IgG and IgA antibodies in NPC sera. Surprisingly, we found that a "low salt" native EA-protein extract reproducibly prepared from purified nuclei of EA-induced HH514 cells, and containing characteristic EA(D)-polypeptides, such as p47-54 (BMRF1), p138 (BALF2), p55-DNAse (BGLF5), and p65-TK (BXLF1), but without viral capsid (VCA) or nuclear antigen (EBNA) reactivity, gave highest sensitivity (90.4%) and specificity (95.5%) values for NPC diagnosis in both IgG and IgA ELISA. The data support further the notion that EBV-EA reactive IgG and IgA antibodies in NPC patients are directed against distinct conformational and-in part-linear epitopes on EBV-specific proteins, barely recognized in other EBV-related syndromes. The use of a defined native EBV EA-specific antigen opens the way to further improve serological diagnosis of NPC. PMID- 17854044 TI - Clinical outcome of renal transplantation in patients with positive pre transplant hepatitis B surface antigen. AB - The clinical outcomes of 2,054 renal recipients were examined retrospectively based on pre-transplant hepatitis B surface antigen (HBsAg) status to investigate the efficacy of lamivudine treatment in HBsAg positive recipients. Pre-transplant HBsAg positivity was documented in 66 recipients. The 10-year patient and graft survival rates in Ag positive group were significantly lower than those of Ag negative group (64.4/36.6% vs. 88.2/70.5%, respectively, P < 0.0001). Since 1997, lamivudine was used when hepatitis B virus polymerase chain reaction (HBV PCR) was positive or when the level of post-transplant viral load rose. Lamivudine given to 27 recipients markedly improved both 10-year patient and graft survivals compared to Ag positive renal recipients who did not take lamivudine (85.3/59.2% vs. 49.9/22.7%, respectively, P < 0.0001). Overall, 13 viral breakthroughs among 24 lamivudine-responsive patients were observed. The cumulative incidence of viral breakthrough at 60 months was 53.3%. Adefovir rescue in three viral breakthroughs patients induces virological response and restoration of liver function. In 10 patients who did not changed to adefovir, 6 patients are alive with elevated liver enzymes. In conclusion, in the era of lamivudine and adefovir, renal transplantation in HBsAg positive end-stage renal disease patients should not be abandoned. PMID- 17854045 TI - Genital herpes due to acyclovir-sensitive herpes simplex virus caused secondary and recurrent herpetic whitlows due to thymidine kinase-deficient/temperature sensitive virus. AB - Herpes simplex virus (HSV)-2 caused a genital ulcer in a 40-year-old allogenic stem cell recipient, and a secondary herpetic whitlow appeared during 2 months of acyclovir (ACV) therapy. Both genital ulcer, and whitlow were cured 3 months later, but 6 months after recovery the whitlow alone recurred. DNA of the genital, first, and recurrent whitlow isolates showed similar endonuclease digestion fragment profiles. The genital virus was ACV-sensitive, and the two whitlow isolates were ACV-resistant/thymidine kinase (TK)-deficient. The TK gene of the whitlow isolates had the same frame shift from the 274th amino acid and termination at the 347th amino acid due to the deletion of a cytosine at the 819th nucleotide. Because the temperature of the thumb is 33/34 degrees C or lower, the temperature sensitivity of the isolates were compared, and both whitlow isolates were significantly more temperature-sensitive (ts) at 39 degrees C than the genital isolate. The two whitlow isolates showed cutaneous pathogenicity in mouse ear pinna but not midflank, while the genital isolate was pathogenic at both sites, suggesting that temperature adaptation was an important element of pathogenicity in the whitlow. The virus populations of isolates of the genital, and first whitlow were examined by 31, and 82 clones, respectively, and the clones from genital, and whitlow isolates were ACV-sensitive, and -resistant, respectively, showing their homogeneity. The acyclovir-sensitive genital lesion had spread as a TK-deficient/ts herpetic whitlow during ACV treatment, and an apparently TK-deficient virus adapted to the local temperature might have caused the whitlow recurrence. PMID- 17854046 TI - Identification of interspecies recombination among hepadnaviruses infecting cross species hosts. AB - Members of the family Hepadnaviridae are divided into two genera, Orthohepadnavirus (from mammalian) and Avihepadnavirus (from avian). Recombination had been found to occur among human hepatitis B virus (HBV) strains of different genotypes, or between hepadnavirus strains from human and nonhuman primate. To reach a comparatively complete inspection of interspecies recombination events among hepadnavirus strains from various hosts, 837 hepadnavirus complete genome sequences from human and 112 from animals were analyzed by using fragment typing to scan for potential interspecies recombinants. Further bootscanning and phylogenetic analyses of the potential recombinants revealed six genome sequences as interspecies recombinants. Interspecies recombination events were found to occur among HBV strains from human and nonhuman primates, from gibbons of different genera, from chimpanzee and an unknown host, and between two avian hepadnavirus strains from birds of different subfamilies, which was identified for the first time. HBV interspecies recombinants were found to have recombination hot spots similar to that of human HBV intergenotype recombinants, breakpoints frequently locating near gene boundaries. Interspecies recombination found in this study may alter current views on hepadnavirus host specificity. PMID- 17854047 TI - Neurophysiological actions of methylphenidate in the primary somatosensory cortex. AB - As a catecholamine reuptake blocker, methylphenidate (MPH) enhances noradrenergic transmission and is likely to influence norepinephrine actions in sensory systems. To characterize neurophysiological actions of MPH in the primary somatosensory (SI) cortex, we recorded basal and whisker deflection-evoked discharge of infragranular sensory cortical neurons, before and after intraperitoneal administrations of saline and MPH (5 mg/kg) in halothane anesthetized rats. MPH had two types of actions on sensory-evoked neuronal responses in the SI cortex, depending on the initial amplitude of the sensory response. When the whisker deflection induced a small excitatory response under control conditions, MPH significantly increased the amplitude of the response by approximately 40%. When the whisker stimulation induced a large excitatory response under control conditions, MPH did not significantly alter the amplitude of the response, but significantly decreased the duration and the peak latency of the response, so that the response was more focused. These neurophysiological actions of MPH may underlie some of the beneficial effects of the drug on sensory processing and attention. PMID- 17854048 TI - Use of accelerator mass spectrometry to measure the pharmacokinetics and peripheral blood mononuclear cell concentrations of zidovudine. AB - The remarkable sensitivity of accelerator mass spectrometry (AMS) is finding many new applications in pharmacology. In this study AMS was used to measure [(14)C] Zidovudine (ZDV) concentrations at the drug's site of action (peripheral blood mononuclear cells, PBMCs) following a dose of 520 ng (less than one-millionth of the standard daily dose) to a healthy volunteer. In addition, the pharmacokinetics of this microdose were determined and compared to previously published parameters for therapeutic doses. Microdose ZDV pharmacokinetic parameters fell within reported 95% confidence intervals or standard deviations of most previously published values for therapeutic doses. Blood, urine, stool, saliva, and isolated PBMCs were collected periodically through 96 h postdose and analyzed for ZDV and metabolite concentrations. The results showed that ZDV is rapidly absorbed and eliminated, has one major metabolite, and is sequestered in PBMCs. (14)C mass balance assessments indicated a significant portion of ZDV remained after 96 h with a much prolonged elimination half-life. Results of this study demonstrate the usefulness of microdosing and AMS as a tool for studying the pharmacokinetic characteristics, including PBMC concentrations, of ZDV and underscore the value of AMS as a tool with which to perform pharmacokinetic and mass balance studies using trace amounts of radiolabeled compound. PMID- 17854049 TI - Synthesis and characterization of a new mebendazole salt: mebendazole hydrochloride. AB - Mebendazole hydrochloride [(5-benzoyl-1H-benzimidazole-2-yl)-carbamic acid methyl ester hydrochloride, MBZ.HCl], a new stable salt of mebendazole (MBZ), has been synthesized and characterized. It can easily be obtained from recrystallization of forms A, B, or C of MBZ in diverse solvents with the addition of hydrochloric acid solution. Crystallographic data reveals that the particular conformation adopted by the carbamic group contributes to the stability of the network. The crystal packing is stabilized by the presence of three N-H...Cl intermolecular interactions that form chains along the b axis. The XRD analyses of the three crystalline habits found in the crystallization process (square-based pyramids, pseudohexagonal plates, and prismatic) show equivalent diffraction patterns. The vibrational behavior is consistent with crystal structure. The most important functional groups show shifts to lower or higher frequencies in relation to the MBZ polymorphs. The thermal study on MBZ.HCl indicates that the compound is stable up to 160 degrees C approximately. Decomposition occurs in four steps. In the first step the HCl group is eliminated, and after that the remaining MBZ polymorph A decomposes in three steps, as happens with polymorphs B and C. ( PMID- 17854050 TI - Prediction of onset of crystallization from experimental relaxation times. II. Comparison between predicted and experimental onset times. AB - Given a good correlation between onsets of crystallization and mobility above T(g), one might be able to predict crystallization onsets at a temperature of interest far below T(g) from this correlation and measurement of mobility at a temperature below T(g). Such predictions require that: (a) correlation between crystallization onset and mobility is the same above and below T(g), and (b) techniques used to measure mobility above and below T(g) measure the same kind of mobility [(b) demonstrated previously using dielectric and calorimetric techniques]. The objective of present work is to determine whether crystallization onset times couple with relaxation times determined above T(g), and if so to verify predictions made below T(g) (from data above T(g)) with experimental data. Model compounds were indomethacin, ketoconazole, flopropione, nifedipine, and felodipine. Onsets of crystallization measured above T(g) were coupled with dielectric mobility for indomethacin, felodipine, and flopropione. Prediction of crystallization onset times for temperatures below T(g) matched well with experimental data for indomethacin (25 degrees C, 35 degrees C: Predicted 473, 95 h; EXPERIMENTAL: 624 +/- 158, 139 +/- 49 h) and flopropione (35 degrees C, 40 degrees C; Predicted 115, 58 h; EXPERIMENTAL: 96 +/- 30, 59 +/- 10 h). The data suggests that coupling between crystallization onsets and molecular mobility at temperatures above T(g) may be exploited to develop stability testing protocol for crystallization from amorphous state. PMID- 17854051 TI - Functional analysis of promoter variants in the microsomal triglyceride transfer protein (MTTP) gene. AB - The microsomal triglyceride transfer protein (MTTP) is required for the assembly and secretion of apolipoprotein B (apoB)-containing lipoproteins from the intestine and liver. According to this function, polymorphic sites in the MTTP gene showed associations to low-density lipoprotein (LDL) cholesterol and related traits of the metabolic syndrome. Here we studied the functional impact of common MTTP promoter polymorphisms rs1800804:T>C (-164T>C), rs1800803:A>T (-400A>T), and rs1800591:G>T (-493G>T) using gene-reporter assays in intestinal Caco-2 and liver Huh-7 cells. Significant results were obtained in Huh-7 cells. The common MTTP promoter haplotype -164T/-400A/-493G showed about two-fold lower activity than the rare haplotype -164C/-400T/-493T. MTTP promoter mutant constructs -164T/ 400A/-493T and -164T/-400T/-493T exhibited similar activity than the common haplotype. Activities of mutants -164C/-400A/-493G and -164C/-400A/-493T resembled the rare MTTP promoter haplotype. Electrophoretic mobility shift assays (EMSAs) revealed higher binding capacity of the transcriptional factor Sterol regulatory element binding protein1a (SREBP1a) to the -164T probe in comparison to the -164C probe. In conclusion, our study indicates that the polymorphism 164T>C mediates different activities of common MTTP promoter haplotypes via SREBP1a. This suggested that the already described SREBP-dependent modulation of MTTP expression by diet is more effective in -164T than in -164C carriers. PMID- 17854052 TI - A hybrid Bayesian-frequentist approach to evaluate clinical trial designs for tests of superiority and non-inferiority. AB - Specification of the study objective of superiority or non-inferiority at the design stage of a phase III clinical trial can sometimes be very difficult due to the uncertainty that surrounds the efficacy level of the experimental treatment. This uncertainty makes it tempting for investigators to design a trial that would allow testing of both superiority and non-inferiority hypotheses. However, when a conventional single-stage design is used to test both hypotheses, the sample size is based on the chosen primary objective of either superiority or non inferiority. In this situation, the power of the test for the secondary objective can be low, which may lead to a large loss of resources. Potentially low reproducibility is another major concern for the single-stage design in phase III trials, because significant findings of confirmatory trials are required to be reproducible. In this paper, we propose a hybrid Bayesian-frequentist approach to evaluate reproducibility and power in single-stage designs for phase III trials to test both superiority and non-inferiority. The essence of the proposed approach is to express the uncertainty that surrounds the efficacy of the experimental treatment as a probability distribution. Then one can use Bayes formula with simple graphical techniques to evaluate reproducibility and power adequacy. PMID- 17854053 TI - Effect of an oral iron chelator or iron-deficient diets on uroporphyria in a murine model of porphyria cutanea tarda. AB - Porphyria cutanea tarda is a liver disease characterized by elevated hepatic iron and excessive production of uroporphyrin (URO). Phlebotomy is an effective treatment that probably acts by reducing hepatic iron. Here we used Hfe(-/-) mice to compare the effects on hepatic URO accumulation of two different methods of hepatic iron depletion: iron chelation using deferiprone (L1) versus iron deficient diets. Hfe(-/-) mice in a 129S6/SvEvTac background were fed 5 aminolevulinic acid (ALA), which results in hepatic URO accumulation, and increasing doses of L1 in the drinking water. Hepatic URO accumulation was completely prevented at low L1 doses, which partially depleted hepatic nonheme iron. By histological assessment, the decrease in hepatic URO accumulation was associated with greater depletion of iron from hepatocytes than from Kupffer cells. The L1 treatment had no effect on levels of hepatic cytochrome P4501A2 (CYP1A2). L1 also effectively decreased hepatic URO accumulation in C57BL/6 Hfe( /-) mice treated with ALA and a CYP1A2 inducer. ALA-treated mice maintained on defined iron-deficient diets, rather than chow diets, did not develop uroporphyria, even when the animals were iron-supplemented either directly in the diet or by iron dextran injection. CONCLUSION: The results suggest that dietary factors other than iron are involved in the development of uroporphyria and that a modest depletion of hepatocyte iron by L1 is sufficient to prevent URO accumulation. PMID- 17854054 TI - Apical and lateral cell protrusions interconnect epithelial cells in live Drosophila wing imaginal discs. AB - Communication among cells by means of the exchange of signaling cues is important for tissue and organ development. Recent reports indicate that one way that signaling cues can be delivered is by movement along cellular protrusions interconnecting cells. Here, by using confocal laser scanning microscopy and three-dimensional rendering, we describe in Drosophila melanogaster wing imaginal discs lateral protrusions interconnecting cells of the columnar epithelium. Moreover, we identified protrusions of the apical surface of columnar cells that reached and apparently contacted cells of the overlying squamous epithelium. Both apical and lateral protrusions could be visualized by expression of Tkv-GFP, a green fluorescent protein (GFP) -tagged version of a receptor of the Dpp/BMP4 signaling molecule, and the endosome marker GFP-Rab5. Our results demonstrate a previously unexpected richness of cellular protrusions within wing imaginal discs and support the view that cellular protrusions may provide a means for exchanging signaling cues between cells. PMID- 17854055 TI - The distribution of the radial and musculocutaneous nerves in the brachialis muscle. AB - Few have examined the distribution of the radial nerve branch to brachialis, generally believed to be motor, within the muscle. We examined the right brachialis muscles of six dissecting room cadavers and found that four received a supply from the radial nerve. The radial nerve branch(es) supplied the inferolateral region of the muscle and was overlapped proximodistally and mediolaterally by the intramuscular branches of the musculocutaneous nerve, which lay on a more superficial plane. The results have implications for the anterolateral approach to the humerus for orthopedic surgery. Anterior splitting of the muscle will almost certainly damage the most lateral branches of the musculocutaneous nerve. PMID- 17854056 TI - Sleeping sites, sleeping trees, and sleep-related behaviors of black crested gibbons (Nomascus concolor jingdongensis) at Mt. Wuliang, Central Yunnan, China. AB - Data on sleep-related behaviors were collected for a group of central Yunnan black crested gibbons (Nomascus concolor jingdongensis) at Mt. Wuliang, Yunnan, China from March 2005 to April 2006. Members of the group usually formed four sleeping units (adult male and juvenile, adult female with one semi-dependent black infant, adult female with one dependent yellow infant, and subadult male) spread over different sleeping trees. Individuals or units preferred specific areas to sleep; all sleeping sites were situated in primary forest, mostly (77%) between 2,200 and 2,400 m in elevation. They tended to sleep in the tallest and thickest trees with large crowns on steep slopes and near important food patches. Factors influencing sleeping site selection were (1) tree characteristics, (2) accessibility, and (3) easy escape. Few sleeping trees were used repeatedly by the same or other members of the group. The gibbons entered the sleeping trees on average 128 min before sunset and left the sleeping trees on average 33 min after sunrise. The lag between the first and last individual entering the trees was on average 17.8 min. We suggest that sleep-related behaviors are primarily adaptations to minimize the risk of being detected by predators. Sleeping trees may be chosen to make approach and attack difficult for the predator, and to provide an easy escape route in the dark. In response to cold temperatures in a higher habitat, gibbons usually sit and huddle together during the night, and in the cold season they tend to sleep on ferns and/or orchids. PMID- 17854057 TI - Survey and comparison of major intestinal flora in captive and wild ring-tailed lemur (Lemur catta) populations. AB - A survey to identify the major intestinal species of aerobic bacteria, protozoa and helminths was conducted on captive and wild populations of ring-tailed lemurs (Lemur catta). Samples were collected from 50 captive lemurs at 11 zoological institutions in the United States. In Madagascar, 98 aerobic bacteria samples and 99 parasite samples were collected from eight sites chosen to cover a variety of populations across the species range. Identical collection, preservation and lab techniques were used for captive and wild populations. The predominant types of aerobic bacteria flora were identified via five separate tests. The tests for parasites conducted included flotation, sedimentation and FA/GC. Twenty-seven bacteria unique to either the captive or wild populations were cultured with eight of these being statistically significantly different. Fourteen bacteria common to both populations were cultured, of which six differed significantly. Entamoeba coli was the only parasite common to both the captive and wild populations. Giardia spp., Isospora spp., strongyles-type ova, Entamoeba spp. and Entamoeba polecki were found only in captive samples. Cryptosporidium, Balantidium coli, pinworm-type ova, and two fluke-like ova were seen only in wild samples. In addition, samples were compared for both bacteria and parasites from three unique field sites in Madagascar. In this three-site comparison, six types of bacteria were statistically significantly different. No significant differences regarding parasites were seen. Significant differences were found between the captive and wild populations, whereas fewer differences were found between sites within Madagascar. Although we isolated Campylobacter and Giardia, all animals appeared clinically healthy. PMID- 17854059 TI - Gas-phase basicities of polyfunctional molecules. Part 1: Theory and methods. AB - The experimental and theoretical methods of determination of gas-phase basicities, proton affinities and protonation entropies are presented in a tutorial form. Particularities and limitations of these methods when applied to polyfunctional molecules are emphasized. Structural effects during the protonation process in the gas-phase and their consequences on the corresponding thermochemistry are reviewed and classified. The role of the nature of the basic site (protonation on non-bonded electron pairs or on pi-electron systems) and of substituent effects (electrostatic and resonance) are first examined. Then, linear correlations observed between gas-phase basicities and ionization energies or substituent constants are recalled. Hydrogen bonding plays a special part in proton transfer reactions and in the protonation characteristics of polyfunctional molecules. A survey of the main properties of intermolecular and intramolecular hydrogen bonding in both neutral and protonated species is proposed. Consequences on the protonation thermochemistry, particularly of polyfunctional molecules are discussed. Finally, chemical reactions which may potentially occur inside protonated clusters during the measurement of gas-phase basicities or inside a protonated polyfunctional molecule is examined. Examples of bond dissociations with hydride or alkyl migrations, proton transport catalysis, tautomerization, cyclization, ring opening and nucleophilic substitution are presented to illustrate the potentially complex chemistry that may accompany the protonation of polyfunctional molecules. PMID- 17854058 TI - A stroma targeted therapy enhances castration effects in a transplantable rat prostate cancer model. AB - BACKGROUND: Castration results in a major involution of the normal prostate gland. This process is initiated by effects in the prostate stroma and vasculature. Castration-induced regression of androgen sensitive prostate tumors is however less prominent and hypothetically this could be related to a limited stromal/vascular response. We therefore used animal tumor models to explore the importance of stroma and vascular effects, and if castration effects could be enhanced by a simultaneous therapy targeting the tumor stroma. METHODS: Using rats with Dunning PAP and H tumors, stereological methods, immunohistochemistry, and Western blotting, we studied the tumor response 7 and 28 days after castration and after the addition of stroma targeted therapies. RESULTS: In the normal ventral prostate (VP) nuclear androgen receptors (AR) were rapidly downregulated after castration. In contrast, the Dunning tumors downregulated the AR in the cancerous epithelium, but not in the surrounding stroma. Vascular regulators such as the angiopoietins, tie 2, and PDGF-Rbeta were not decreased in the stroma after castration, as observed in the VP, creating an environment that prevents vascular involution. When a tumor stroma targeted therapy inhibiting the tie 2 receptor and the PDGF-Rbeta simultaneously was added to castration it resulted in a decreased vascular density, increased tumor cell apoptosis and decreased tumor growth compared to castration alone. CONCLUSIONS: The stroma in highly differentiated androgen sensitive Dunning tumors is apparently androgen insensitive. If this unresponsive stroma is targeted the effects of castration can be enhanced. PMID- 17854061 TI - beta-Catenin signaling in biological control and cancer. AB - A coordinated integration of cell-cell adhesion and the control of gene expression is essential for the development of multicellular, differentiated organisms. beta-Catenin fulfils important regulatory functions in both cell-cell adhesion by linking cadherin adhesion receptors to the cytoskeleton, and also as a key element in the Wnt signaling pathway where it acts as cotranscriptional activator of target genes in the cell nucleus. Wnt signaling is involved in numerous aspects of embryonic development and in the control of tissue self renewal in a variety of adult tissues. Hyperactivation of Wnt signaling, mostly by affecting beta-catenin functions, is a hallmark of colon cancer and of many other human cancers. In this prospect, we discuss studies pointing to the molecular mechanisms that govern the integration between cell-cell adhesion and gene expression, as reflected in the switches between these two functions of beta catenin in colon cancer cells. PMID- 17854062 TI - Sumatriptan succinate transdermal delivery systems for the treatment of migraine. AB - We have successfully obtained sumatriptan transdermal systems with different polymer compositions: methyl cellulose (MC), polyvinyl pyrrolidone (PVP) and a polyvinyl pyrrolidone (PVP)-polyvinyl alcohol (PVA) mixture. The systems contained 1,2-propylenglycol (MC) or sorbitol as a plasticizer (PVP and PVP-PVA), methacrylate copolymer as an adhesive agent, and an occlusive liner. Azone (5%, w/w) was incorporated into all the systems as a percutaneous enhancer. Transdermal systems are thin, transparent and non-adhesive when in a dry state. The permeation of sumatriptan succinate across pig ear skin was studied using the systems prepared. The formulation with MC polymer produced a statistically significant increment with respect to the PVP and PVP-PVA formulations (p < 0.05). Azone incorporation into the systems produced an increment in the sumatriptan flux values of all three transdermal systems with respect to those of the controls (p < 0.05). In addition, the application of iontophoresis to the wet methyl cellulose-Azone formulation produced a much higher increase of sumatriptan transdermal flux. PMID- 17854063 TI - Molecular and functional expression of multidrug resistance-associated protein-1 in primary cultured rat alveolar epithelial cells. AB - Multidrug resistance-associated protein-1 (MRP1) is an integral membrane efflux protein that is implicated in multidrug resistance in cancer, but it is also expressed in normal tissues. The objective of this study was to determine the expression, localization and functional activity of MRP1 in primary cultured rat alveolar epithelial cells of types I- and II cell-like phenotypes. RT-PCR data showed 550-base pair fragments in both types I- and II-like pneumocytes that exhibited 99% identity to the rat MRP1 isoform. Significant levels of MRP1 protein were detected by western analysis of immunoprecipitates in both cell types, and immunofluorescence combined with confocal laser scanning microscopy indicated basolateral localization of MRP1. Indomethacin (0-100 microM) increased fluorescein basolateral-to-apical transport, and accumulation of fluorescein in the cells, in a dose-dependent manner. We therefore conclude that the MRP1 gene is present in primary cultured rat epithelial cells of both types I- and II-like phenotypes and its corresponding protein (MRP1) is localized in the basolateral membrane of these cells. Primary cultured monolayers of rat type II-like pneumocytes appear to be a useful tool for screening MRP1 substrates designed for pulmonary delivery/targeting. PMID- 17854064 TI - Preparation and characteristics of nano-grained calcium phosphate coatings on titanium from ultrasonated bath at acidic pH. AB - Electrochemically deposited nano-grained calcium phosphate coatings were produced on titanium substrates using aqueous electrolyte at acidic pH. Different coatings were produced by using cathodic current densities ranging from 10 to 50 mA/cm(2) from an ultrasonated electrolytic bath. These coatings contained dicalcium phosphate dihydrate as the predominant phase and hydroxyapatite as the minor phase. With increasing current density, hydroxyapatite content in the coatings increased. Dicalcium phosphate grains had size in the range of 55-85 nm and hydroxyapatite had grains in the size range of 20-25 nm. Scanning electron microscopy showed that the morphology of the coatings obtained at lower current densities had acicular structure. With increasing current densities, the needles became blunt and small and finally, at 50 mA/cm(2) the coating had globular deposits. Surface roughness of the coatings also increased with increasing deposition current density. Tensile bond strengths of the coatings were in the range of 3.6-6.9 MPa and decreased with increase of deposition current density. Heat-treatment of the coatings for 2 h at 500 degrees C completely eliminated the dicalcium phosphate phase and resulted in mono hydroxyapatite phase containing grains in the size range of 20-30 nm. PMID- 17854065 TI - Laboratory markers of thrombosis risk in children with hereditary spherocytosis. AB - BACKGROUND: Recent data suggest that adults with hereditary spherocytosis (HS) may be protected from atherothrombosis before splenectomy but have increased risk of thrombosis following splenectomy. In order to aid in making informed decisions regarding splenectomy in children with HS, we conducted a retrospective study of several surrogate laboratory markers of thrombosis risk in children with HS. METHODS: A retrospective record review was performed on 246 children with HS. Platelet count and hemoglobin concentration were recorded prior to and following splenectomy in each patient. Serum cholesterol levels were collected from the record when available. RESULTS: Prior to splenectomy, hypocholesterolemia was common. Mean platelet counts in 31 evaluable patients pre- and post-splenectomy were 334 and 608 x 10(9)/L, respectively (P < 0.001). Twenty-nine patients (94%) exhibited persistent thrombocytosis following splenectomy. Hemoglobin values following splenectomy often rose to higher than age and gender-matched norms, with 30% of measurements greater than the 90th percentile and 17% greater than the 97th percentile. CONCLUSIONS: The findings of hypocholesterolemia before splenectomy and thrombocytosis and mild polycythemia afterwards support the hypothesis that patients with HS might be protected from thrombosis before splenectomy and/or more susceptible afterwards. Prospective studies of additional prothrombotic biomarkers and thrombotic events in HS patients are warranted. PMID- 17854066 TI - Copolymerization of D,L-lactide and glycolide in supercritical carbon dioxide with zinc octoate as catalyst. AB - The objective of the study is the development of a new technique based on supercritical technology for the production of bioabsorbable polymeric microparticles containing pharmaceutical principles, for their use in the controlled release of medicines. For this purpose, the ring-opening copolymerization of D,L-lactide and glycolide in supercritical carbon dioxide, using zinc(II) 2-ethylhexanoate (ZnOct2) as catalyst, was studied. The polymer obtained with ZnOct2 has similar characteristics to that obtained with stannous octoate (SnOct2), the conventional catalyst used up to now for this kind of polymerization process. Experiments were performed at various reaction times, pressures, and stirring rates. The most outstanding result was found by varying the stirring rate, where particles forming agglomerates seem to be obtained at the greater agitation levels. PMID- 17854067 TI - An antimicrobial TiO2 coating for reducing hospital-acquired infection. AB - Titanium dioxide (TiO2) has been developed and applied extensively in the form of coatings, in particular for its unique properties such as non-toxicity, high photocatalytic activity, and strong self-cleaning ability. These coatings, which can be prepared via various processes, have not yet been proved to be antimicrobial. This research involves an arc ion plating method to produce TiO2 film on medical grade AISI 304 stainless steel. Antimicrobial efficacy of the deposits is expected due to the photocatalysis action of the anatase phase presented in the deposit. The performance of the coating is evaluated by a JIS Z2801:2000 industrial standard. Experimental results show that TiO2 film mainly consisting of anatase structure can be prepared with a high growth rate of 5 microm/h. Antimicrobial activity (R) of the deposited TiO2 film against Staphylococcus aureus and Escherichia coli was 3.0 and 2.5, respectively, far beyond the value designated in JIS standard. This provides an effective antimicrobial surface coating method for medical implements thereby reducing the risk of hospital-acquired infections. PMID- 17854068 TI - Hydrophilic biodegradable microspheres of interferon-alpha and its pharmacokinetics in mice. AB - The goal of this research was to prepare a kind of hydrophilic sustained release microspheres of interferon-alpha (IFN-alpha), alginate-chitosan microspheres (ACM) of IFN, and investigate its pharmacokinetics in mice. Alginate microspheres of IFN-alpha were first prepared by an emulsion method and further incubated in chitosan to form IFN-ACM. The influences of isopropanol, bovine serum albumin (BSA), and pH adjustment by isoelectric point of IFN were studied. The optimized IFN-ACM was obtained with smooth and round morphology, size of 2.18 +/- 0.43 microm and entrapment efficiency of 40%. All the concentrations of IFN-alpha were determined by IFN assay kits. Finally the pharmacokinetics of IFN-ACM suspension was studied in ICR mice by intramuscular (I.M.) routes. Compared with IFN solution, C(max) of IFN-ACM reduced 2.3-fold, and time to achievement of maximum serum concentrations (T(max)) increased 4-fold. Meanwhile the area under the concentration-time curve (AUC) was the same as that of solution. The concentration-time profiles presented the prolonged serum levels of IFN from IFN ACM. PMID- 17854069 TI - Transfer of metallic debris from the metal surface of an acetabular cup to artificial femoral heads by scraping: comparison between alumina and cobalt chrome heads. AB - We aimed to investigate the transfer of metal to both ceramic (alumina) and metal (cobalt-chrome) heads that were scraped by a titanium alloy surface under different load conditions. The ceramic and metal heads for total hip arthroplasties were scraped by an acetabular metal shell under various loads using a creep tester. Microstructural changes in the scraped area were visualized with a scanning electron microscope, and chemical element changes were assessed using an energy dispersive X-ray spectrometry. Changes in the roughness of the scraped surface were evaluated by a three-dimensional surface profiling system. Metal transfer to the ceramic and metal heads began to be detectable at a 10 kg load, which could be exerted by one-handed force. The surface roughness values significantly increased with increasing test loads in both heads. When the contact force increased, scratching of the head surface occurred in addition to the transfer of metal. The results documented that metallic debris was transferred from the titanium alloy acetabular shell to both ceramic and metal heads by minor scraping. This study suggests that the greatest possible effort should be made to protect femoral heads, regardless of material, from contact with metallic surfaces during total hip arthroplasty. PMID- 17854070 TI - Preliminary assessment of natal attraction and infant handling in wild Colobus vellerosus. AB - This study describes natal attraction and infant handling in wild ursine colobus (Colobus vellerosus). Focal animal samples were collected from five infants of 1 16 weeks of age (mean: 14.5 focal hours per infant). Group members may be attracted to an infant, but unable to handle it because of resistance from the mother. We thus measured natal attraction independently from infant handling by the number of interactive approaches received. The youngest infants were most attractive. Immature females were attracted to and handled infants more than other group members. Mothers were tolerant of most handling attempts and infant directed aggression was rare. A sixth infant was attacked by members of an all male band, which allowed us to record the expression of natal attraction and infant handling in the context of an acute threat of infanticide. This infant was carried by non-mothers less frequently than the other infants, and its mother resisted handling attempts more often. PMID- 17854071 TI - Behaviors in rhesus monkeys (Macaca mulatta) associated with activity counts measured by accelerometer. AB - There are large individual differences in the daily pattern and level of physical activity in humans and other species. As it is becoming apparent that activity plays an integral role in a number of physiological processes including arousal, attention, cardiovascular health and body weight regulation, there is an increased interest in quantifying activity. Nonhuman primates are particularly useful experimental models for such studies in that they exhibit a repertoire of activity more similar to humans than the activity of animals such as rodents and domestic animals. Recent studies measuring activity in nonhuman primates have used omnidirectional accelerometers, often worn on collars; however, the exact behaviors and movements detected by monkeys wearing these devices have not yet been characterized. To test the hypothesis that collar-worn accelerometers primarily detect movements that involve movement of the whole body, 16 adult female rhesus monkeys, housed individually in stainless steel cages, wore loose fitting collars with an attached small metal box housing an activity monitor (Actical omnidirectional accelerometer; MiniMitter Inc., Bend, OR) and behavior was videotaped. Videotaped behaviors were analyzed by frame-by-frame analysis. There was a significant correlation between total (all) movement revealed by videotape analysis and activity counts detected by the accelerometers (r(s)=0.612, P=0.012), primarily reflecting a strong correlation between whole body movement and activity counts (r(s)=0.647, P=0.007). In contrast, arm movement (r(s)=-0.221, P=0.412) and head/neck movement (r(s)=0.193, P=0.474) were not correlated with activity counts. These findings support the hypothesis that activity monitor placement on a collar allows for effective quantification of whole body movement in monkeys, and indicate that behaviors such as chewing and arm movement do not significantly influence activity recorded by collar-mounted accelerometers. PMID- 17854072 TI - Despotic wild patas monkeys (Erythrocebus patas) in Kala Maloue, Cameroon. AB - The socio-ecological model predicts that the quality, distribution, and patch size of food resources determines the dominance hierarchy of female monkeys based on the type of food competition they experience. Comparative studies of closely related species have evaluated the socio-ecological model and confirmed its validity. For example, female patas monkeys in Laikipia, Kenya, form a nonlinear and unstable dominance hierarchy (i.e., egalitarian), whereas females of sympatric, closely related savannah monkeys form a linear and stable dominance hierarchy (i.e., despotic), in accordance with the model's predictions of the characteristics of food resources. I compared agonistic interactions involving food between patas monkeys (Erythrocebus patas) and sympatric savannah monkeys (Cercopithecus aethiops) in Kala Maloue, Cameroon. I found linear dominance hierarchies not only in savannah monkeys, but also in patas monkeys in Kala Maloue. The rates of agonistic interactions during feeding between patas monkeys were equivalent to those between savannah monkeys in Kala Maloue; further, these rates were significantly higher than those of both Laikipia patas and savannah monkeys. The results imply that patas monkeys in Kala Maloue are not egalitarian, but are despotic, similar to savannah monkeys. Disparity in the dominance hierarchies of patas monkeys between Kala Maloue and Laikipia were attributable to the differences in the characteristics of food resources. Although patas monkeys in Laikipia subsist on small and dispersed food resources within a high density area, those in Kala Maloue subsisted on food resources that were clumped in intermediate-sized patches within a low-density area. This study shows that the socio-ecological model is applicable not only for interspecific comparisons but also for intraspecific comparisons. PMID- 17854073 TI - Studies on the crystal forms of pefloxacin: preparation, characterization, and dissolution profile. AB - Different crystal forms of pefloxacin were prepared using solvents of varying polarity. X-ray diffractometry (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), infrared absorption spectroscopy (FT-IR), melting point, microcalorimetry and in vitro dissolution rate studies were conducted to investigate various characterstics of different crystalline forms of the pefloxacin. Five different polymorphs of pefloxacin have been identified on the basis of instrumental techniques. The polymorphs differed in their dissolution profile and all of them showed unusual behavior of highest dissolution in the first 15 min. The rate of dissolution went on decreasing and got stabilized to a constant value after 4 h. PMID- 17854074 TI - Cytotoxicity and apoptosis enhancement in brain tumor cells upon coadministration of paclitaxel and ceramide in nanoemulsion formulations. AB - The objective of this study was to examine augmentation of therapeutic activity in human glioblastoma cells with combination of paclitaxel (PTX) and the apoptotic signaling molecule, C(6)-ceramide (CER), when administered in novel oil in-water nanoemulsions. The nanoemulsions were formulated with pine-nut oil, which has high concentrations of essential polyunsaturated fatty acid (PUFA). Drug-containing nanoemulsions were characterized for particle size, surface charge, and the particle morphology was examined with transmission electron microscopy (TEM). Epi-fluorescent microscopy was used to analyze nanoemulsion encapsulated rhodamine-labeled PTX and NBD-labeled CER uptake and distribution in U-118 human glioblastoma cells. Cell viability was assessed with the MTS (formazan) assay, while apoptotic activity of PTX and CER was evaluated with caspase-3/7 activation and flow cytometry. Nanoemulsion formulations with the oil droplet size of approximately 200 nm in diameter were prepared with PTX, CER, and combination of the two agents. When administered to U-118 cells, significant enhancement in cytotoxicity was observed with combination of PTX and CER as compared to administration of individual agents. The increase in cytotoxicity correlated with enhancement in apoptotic activity in cells treated with combination of PTX and CER. The results of these studies show that oil-in-water nanoemulsions can be designed with combination therapy for enhancement of cytotoxic effect in brain tumor cells. In addition, PTX and CER can be used together to augment therapeutic activity, especially in aggressive tumor models such as glioblastoma. PMID- 17854075 TI - Selection of dosing regimen with WST11 by Monte Carlo simulations, using PK data collected after single IV administration in healthy subjects and population PK modeling. AB - WST11, a novel generation of photo sensitizers to be used for vascular-targeted phototherapy (VTP), is effective at short interval between injection and illumination and it is expected to enable selective destruction of neovasculature with minimal side effects or skin photo toxicity. This study was conducted to evaluate the clinical and laboratory safety, tolerability and pharmacokinetic profile of WST11 given as a single intravenous administration (1.25, 2.5, 5, 7.5, 10, or 15 mg/kg) during an escalating dose study in healthy male subjects. This article describes WST11 population pharmacokinetic modeling and simulations performed to optimize the IV infusion-dosing regimen in combination with illumination, the target PK profile being plateau concentrations during approximately 30 min. The study included 42 healthy male subjects, administered 1.25, 2.5, 5, 7.5, 10, or 15 mg/kg as a 10-min IV infusion. A population pharmacokinetic model was developed using nonlinear mixed effects modeling (NONMEM). Monte Carlo simulations of the population PK dataset (NONMEM) were performed to select series of dosing regimen which would result in a plateau of concentration lasting at least 30 min and allow laser illumination. A two compartment model with nonlinear elimination best described the data. No demographic factor was shown to affect the WST11 pharmacokinetics. The clearance was shown to decreases with the dose administered, ranging from 6 L/h (dose of 79 mg) to 2 L/h (dose of 1110 mg). The duration of the infusion was estimated at 12 min. The volume of distribution of the central compartment was 3 L and the volume of the peripheral compartment was 1.15 L. The apparent inter-compartmental clearance was 0.137 L/h. The between subjects variability on clearance and on volume was low. Residual variability was moderate with a CV of 21%. Due to the dose effect on clearance and the rapid elimination, simulations showed that different dosing inputs are necessary: for 5 and 10 mg/kg BW, a sufficiently good dosing scenario is to administer 80% of the dose over 5 min, 15% over 10 min and the remaining 5% over 10 min. For lower doses, the sequence 70% in 5 min/20% in 10 min/10% in 10 min is preferable. The pharmacokinetic profile of WST11 by IV administration would allow a treatment by laser illumination in good clinical conditions using controlled infusions. The study results do not indicate that the dose should be adjusted for body size. The only factor that determines the drug input profile is the dose level, since the elimination half-life decreases when the dose administered increases. The use of the population PK model for simulations has shown that, at dose level of 5 mg/kg or more, a loading dose of 80% dose given over 5 min followed by 15% of dose during 10 min and remained dose to give over 10 min would result in a favorable PK profile. PMID- 17854077 TI - Non-gynecologic cytology on liquid-based preparations: A morphologic review of facts and artifacts. AB - Liquid-based preparations (LBP) are increasingly being used both for gynecologic (gyn) and non-gynecologic (non-gyn) cytology including fine needle aspirations (FNA). The two FDA-approved LBP currently in use include ThinPrep (TP), (Cytyc Corp, Marlborough, MA) and SurePath (SP), (TriPath Imaging Inc., Burlington, NC). TP was approved for cervico-vaginal (Pap test) cytology in 1996 and SP in 1999 and both have since also been used for non-gyn cytology. In the LBP, instead of being smeared, cells are rinsed into a liquid preservative collection medium and processed on automated devices. Even after a decade of use, the morphological interpretation of LBP remains a diagnostic challenge because of somewhat altered morphology and artifacts or facts resulting from the fixation and processing techniques. These changes include cleaner background with altered or reduced background and extracellular elements; architectural changes such as smaller cell clusters and sheets, breakage of papillae; altered cell distribution with more dyscohesion and changes in cellular morphology with enhanced nuclear features, smaller cell size and slightly more three-dimensional (3-D) clusters. Herein, we review the published literature on morphological aspects of LBP for non-gyn cytology. PMID- 17854076 TI - A variant of the Cockayne syndrome B gene ERCC6 confers risk of lung cancer. AB - Cockayne syndrome B protein (ERCC6) plays an essential role in DNA repair. However, the Cockayne syndrome caused by the ERCC6 defect has not been linked to cancer predisposition; likely due to the fact that cells with severe disruption of the ERCC6 function are sensitive to lesion-induced apoptosis, thus reducing the chance of tumorigenesis. The biological function and cancer susceptibility of a common variant rs3793784:C>G (c.-6530C>G) in the ERCC6 was examined. We show that the c.-6530C allele has lower binding affinity of Sp1 by EMSA and displays a lower transcriptional activity in vitro and in vivo. We then examined the contribution of this polymorphism to the risk of lung cancer in a case-control study with 1,000 cases and 1,000 controls. The case-control analysis revealed a 1.76-fold (P= x 10(-9)) excess risk of developing lung cancer for the c.-6530CC carriers compared with noncarriers. The c.-6530CC interacts with smoking to intensify lung cancer risk, with the odds ratio (OR)=9 for developing lung cancer among heavy smokers. Our data constituted strong evidence that ERCC6 rs3793784:C>G alters its transcriptional activity and may confer personalized susceptibility to lung cancer. PMID- 17854078 TI - Symptomatic candidiasis: Using self sampled vaginal smears to establish the presence of Candida, lactobacilli, and Gardnerella vaginalis. AB - In a prospective cohort study, 10 symptomatic women with recurrent vulvovaginal candidiasis were taught how to prepare vaginal smears of their own vaginal fluids on days 7, 14, 21, and 28. The 40 smears were stained with the PAS-method and examined by three different cytopathologists for presence of Candida. Thereafter, the smears were restained with Giemsa-stain to determine presence of lactobacilli, Gardnerella vaginalis ("clue cells") and neutrophils. All three cytopathologists unequivocally established Candida blastospores and (pseudo)hyphae in 27 out of the 40 PAS-stained vaginal smears, whereas in the remaining 13 smears Candida was not found. All 10 patients had Candida in their smears during the second half of their menstrual cycle.Self sampled smears prove to be reliable for establishing the presence of Candida in symptomatic patients with candidiasis. Candida is associated with a lactobacillus-predominated vaginal flora, but with the absence of Gardnerella vaginalis. Further studies may be directed towards the interaction between the various members of the vaginal flora. This study should open molecular methodology for determining the possible interactions of lactobacilli and Candida. PMID- 17854079 TI - Comparison of cell block preparation methods for nongynecologic ThinPrep specimens. AB - The purpose of this study was to compare four cell block (CB) methods in the setting of nongynecologic ThinPrep (TP) specimens. 48 CBs were prepared from 12 nongynecologic TP specimens using the following CB methods: (1) Inverted filter sedimentation (IFS); (2) Thrombin method; (3) Albumin method; (4) Simple sedimentation. Each CB was assigned a cellularity score: 0 no cells, 1+ hypocellular, 2+ hypocellular with tissue fragments, 3+ cellular. A score of 2+ or 3+ was given for 11/12 of thrombin, 7/12 IFS, 5/12 albumin, and 2/12 simple sedimentation CBs. Thrombin CBs demonstrated a pale background clot with evenly distributed cells. Albumin CBs had a cracked uneven background. IFS CBs had a clear background, but were technically difficult and cells appeared artifactually crowded. In the setting of nongynecologic TP specimens, the thrombin CB was easily prepared and produced the best CB in regards to cellularity, cell distribution, and background quality. PMID- 17854080 TI - The utility of SMAD4 as a diagnostic immunohistochemical marker for pancreatic adenocarcinoma, and its expression in other solid tumors. AB - Pancreatic adenocarcinoma is a genetic disease showing somatic mutations of multiple genes, including SMAD4. SMAD4 is a tumor suppressor gene that is inactivated in a sub-set of pancreatic adenocarcinoma, either by the intragenic mutation of one allele in combination with the loss of the other allele or by homozygous deletion of both alleles. This study examines SMAD4 expression in fine needle aspiration cell blocks from patients with pancreatic adenocarcinoma, as well as a variety of human cancers, in order to assess its viability as a tumor marker. A total of 100 patients with pancreatic adenocarcinoma, with diagnostic material from fine-needle aspiration cell blocks were selected for this study. In addition cancers from different sites were examined in multitumor tissue microarrays, which included two tissue cores from neoplastic surgical resection specimens. Cancers studied included endometrium (n = 100), colon (n = 100), ovary (n = 100), lung (n = 100), breast (n = 100), and malignant melanoma (n = 100). The sections were immunostained with SMAD4 using pressure cooker antigen retrieval labeled polymer horseradish peroxidase (DAKO), and the DAKO autostainer. Immunohistochemical expression was scored as negative, 1+, 2+, 3+. Only 2+ and 3+ staining was considered as positive staining. SMAD4 staining was nuclear and the results for tumor cell positivity for primary sites studied are as follows: Pancreas (80/100; 80%), endometrium (0/100; 0%), colon (0/100; 0%), ovary (3/100; 3%), lung (0/100; 0%), breast (2/100; 2%), and malignant melanoma (4/100; 4%). This study suggests that SMAD4 is an important marker for confirming a diagnosis of pancreatic adenocarcinoma as a primary tumor, as well as when it presents as a metastatic tumor on small fine-needle aspirate samples. PMID- 17854081 TI - Schistosoma haematobium in urine: morphology with ThinPrep method. PMID- 17854082 TI - Diagnostic value of telomerase expression in breast fine-needle aspiration biopsies. AB - Fine-needle aspiration biopsy (FNAB) of breast is a minimally invasive sampling procedure with a proven value in the initial evaluation of patients with palpable breast lesions. FNAB is a simple, cost-effective, and relatively nontraumatic procedure that has replaced open surgical biopsy in majority of academic institutions across the world. There are, however, inherent limitations in the ability of FNAB to reliably diagnose small percentage of cases that are difficult to diagnose by cytomorphology alone and require excisional biopsy. This shortcoming may be minimized if the morphology can be complemented by a reliable diagnostic adjunct. This retrospective study was designed to assess the added value of telomerase immunostain in interpretation of breast FNABs. Telomerase is a ribonucleoprotein enzyme that has been shown to be activated in different malignant tumors, including breast cancer. Immunocytochemical detection of this molecular marker on cytologic smears and cellblocks may be helpful for interpretation of FNAB specimens. In our retrospective study, we found that 56% of the malignant breast cases (28/50) showed positive telomerase immunostaining while only 4% of the negative cases (2/50) stained with telomerase (positive predictive value: 93%, negative predictive value: 69%). Expression of telomerase on highly suspicious breast fine-needle aspirations may upgrade the diagnosis to malignancy. However, a negative telomerase cannot exclude the possibility of carcinoma. PMID- 17854083 TI - Use of imprint cytology for assessment of surgical margins in lumpectomy specimens of breast cancer patients. AB - In the past several years, breast-conservation therapy has provided an alternative to mastectomy. In order to reduce the subsequent local tumor recurrence, it is critical that all the measures are in place to find the residual foci of occult microscopic tumor at the time of the initial lumpectomy procedure. An accepted method to evaluate the lumpectomy margins for presence of residual tumor is the use of imprint cytology (also called touch-prep), which is assessment of the presence or absence of the tumor cells by cytological preparation. This is a rapid, cost effective, and easy to use procedure with added advantage of saving tissue for permanent sectioning and rendering a definitive diagnosis. In this report, we present our experience using intraoperative imprint cytology for evaluation of the status of lumpectomy specimens in breast cancer patients. The objective of this study was to evaluate the diagnostic accuracy of intraoperative imprint cytology for assessment of surgical resection margins in lumpectomy margins of patients with breast carcinoma. This is a retrospective study of 100 cases of breast lumpectomy specimens, which had undergone intraoperative imprint cytology. The cases were retrieved from the archived files of the University of Florida, Department of Pathology at Shands Jacksonville. The results of intraoperative imprint cytology were compared with the histological findings of the corresponding permanent sections of the same cases as the gold standard. Overall, we reviewed 510 cytology imprint slides, which were obtained from 100 lumpectomy specimens. Among these cases, 37 slides from 22 cases were reported positive and the remaining were negative. Only eight slides from six cases of lumpectomy showed discrepancy between the result of intraoperative imprint cytology and the permanent sections of the same cases. In our study, intraoperative imprint cytology showed a sensitivity of 97%, specificity of 99%, with positive predictive value of 84%, and negative predictive value of 99%. This study demonstrates that intraoperative imprint cytology can be used as a reliable diagnostic procedure for the evaluation of the status of lumpectomy margins in breast cancer patients. PMID- 17854084 TI - Repeating cytological preparations on liquid-based cytology samples: A methodological advantage? AB - This study investigates the rule that repeating cytological preparations on liquid-based cytology improves sample adequacy, diagnosis, microbiological, and hormonal evaluations. We reviewed 156 cases of pap-stained preparations of exfoliated cervical cells in two slides processed by DNA-Cytoliq System. After sample repeat/dilution, limiting factors affecting sample adequacy were removed in nine cases and three unsatisfactory cases were reclassified as satisfactory. Diagnosis was altered in 24 cases. Of these, the original diagnosis in 15 was atypical squamous cells of undetermined significance; after the second slide examination, diagnosis in 5 of the 15 cases changed to low-grade squamous intraepithelial lesion, 3 to high-grade squamous intraepithelial lesion, and 7 to absence of lesion. Microbiological evaluation was altered, with Candida sp. detected in two repeated slides. Repeat slide preparation or dilution of residual samples enhances cytological diagnosis and decreases effects of limiting factors in manually processed DIGENE DCS LBC. PMID- 17854085 TI - Gynecological cytology: too old to be a pop star but too young to die. PMID- 17854086 TI - Brown oval structures in vaginal Thin Prep smear: What could they be? PMID- 17854087 TI - Leptomeningeal metastasis in a patient with squamous cell carcinoma of the uterine cervix: Report of a case and review of the literature. AB - Leptomeningeal spread of advanced squamous cell carcinoma (SCC) of the uterine cervix is unusual. To our knowledge, very few cases were reported in the English literature. We report a case of a 39-yr-old woman who presented with leptomeningeal metastasis from a stage IIb SCC of uterine cervix. The diagnosis was made by cytomorphological examination of smears obtained from cerebrospinal fluid. The cytomorphological features are demonstrated. PMID- 17854088 TI - Cytological diagnosis of cryptococcal peritonitis on peritoneal fluid. PMID- 17854089 TI - Metastatic hepatocellular carcinoma to the mandible masquerading as a parotid gland mass: A potential pitfall in the diagnosis by fine needle aspiration biopsy. PMID- 17854090 TI - Array-MLPA: comprehensive detection of deletions and duplications and its application to DMD patients. AB - Multiplex ligation-dependent probe amplification (MLPA) is widely used to screen genes of interest for deletions and duplications. Since MLPA is usually based on size-separation of the amplification products, the maximum number of target sequences that can be screened in parallel is usually limited to approximately 40. We report the design of a robust array-based MLPA format that uses amplification products of essentially uniform size (100-120 bp) and distinguishes between them by virtue of incorporated tag sequences. We were thus able to increase probe complexity to 124, with very uniform product yields and signals that have a low coefficient of variance. The assay designed was used to screen the largest set studied so far (249 patients) of unrelated Duchenne muscular dystrophy (DMD) cases from the Chinese population. In a blind study we correctly assigned 98% of the genotypes and detected rearrangements in 181 cases (73%); i.e., 163 deletions (65%), 13 duplications (5%), and five complex rearrangements (2%). Although this value is significantly higher for Chinese patients than previously reported, it is similar to that found for other populations. The location of the rearrangements (76% in the major deletion hotspot) is also in agreement with other findings. The 96-well flow-through microarray system used in this research provides high-throughput and speed; hybridization can be completed in 5 to 30 minutes. Since array processing and data analysis are fully automated, array-MLPA should be easy to implement in a standard diagnostic laboratory. The universal array can be used to analyze any tag-modified MLPA probe set. PMID- 17854093 TI - Role of vitamin A elimination or supplementation diets during postnatal development on the allergic sensitisation in mice. AB - Vitamin A (VA) and its derivatives, the retinoids, are important factors for the development of the immune system. It has been shown in adult animals that proliferation of lymphocyte populations and antibody secretion are retinoid dependent, while little is known about the effects of retinoids during postnatal development. The aim of this study was to investigate the role of VA on allergic sensitisation during lactation and after weaning using an in vivo system for postnatal allergic sensitisation in mice. Different VA diets (basal/VA elimination/VA (as retinyl palmitate) supplemented) were fed to the dams throughout lactation and directly to the pups after weaning. Allergic sensitisation was induced with a single peritoneal ovalbumin (OVA) injection at day 28 after weaning. The phenotype of lymphocytes was analysed by flow cytometry and functional data were obtained by analysis of (IL-4/IFN-gamma) cytokine production and antibody production (OVA-specific IgG1 and IgE) in the offspring. VA/retinyl palmitate supplementation during lactation and after weaning decreased CD3+, CD4+, CD8+ and B220+ populations in splenic lymphocytes but also significantly enhanced IL-4 production and OVA-specific IgE after sensitisation. In contrast, mice fed VA-elimination diet displayed no significant alteration of lymphocyte numbers and a slightly increased IL-4 production. Our results showed that a single allergen injection during postnatal development induces allergic sensitisation whose degree is modified by the VA content of the maternal diet during lactation and the diet of the pups after weaning, indicating an important role of VA on the severity of the allergic sensitisation. PMID- 17854094 TI - Comments on an MNF review about ochratoxin A. PMID- 17854097 TI - Surgical emphysema: a rare complication following cochlear implantation. AB - A case report of surgical emphysema following adult cochlear implantation. The clinical picture, investigations and management of this rare case will be discussed. PMID- 17854098 TI - Skin flap thickness in cochlear implant patients - a prospective study. AB - The thickness and quality of the skin overlying a cochlear implant is important for its integrity. It should be thick enough to protect the implant and prevent flap breakdown yet should not be so thick that it impedes the electronic signal or causes difficulty wearing the coil because of loss of the magnetic coupling. The principle of this study was to devise a method to assess the thickness of skin over a cochlear implant receiver stimulator package and prospectively measure this thickness during the first year following surgery. All patients studied were implanted with MED-EL COMBI 40+ implants. The first cohort consisted of 35 adults; the second 23 children. Various methods of measurement were assessed. In this study the principle of the Hall Effect electrode was used to measure the magnetic flux density of the magnet within the receiver stimulator package. Following standardization, results showed that skin thickness significantly thinned in the adult group before stabilizing. This was less obvious in children, probably due to the effect of the skin thickening as the child grows. Knowledge of skin thickness has implications relating to the functioning of an implant and avoiding potential flap related complications. PMID- 17854099 TI - Effects of steroids and lubricants on electrical impedance and tissue response following cochlear implantation. AB - The present study examined the effects of steroids and lubricants on electrical impedance and tissue response following cochlear implantation in animal models. Guinea pigs were implanted following either no treatment, or intrascalar injection with dexamethasone, triamcinolone, sodium hyaluronate or saline. Cats were implanted following either no treatment, or intrascalar injection with dexamethasone, triamcinolone or a mixture of triamcinolone with sodium hyaluronate. In guinea pigs, impedance changes and intracochlear tissue response were less for the hyaluronate and saline groups. In cats, impedance in the dexamethasone group increased similar to non-treated cats. Impedance of triamcinolone treated cats remained low for about two months after implantation, before increasing to levels similar to the other groups. Significant fibrous tissue growth was observed histologically. The results of the present study indicate that a single intracochlear application of hyaluronate or triamcinolone may postpone, but will ultimately not prevent the rise in impedance following cochlear implantation. PMID- 17854100 TI - Unexpected exit of a cochlear implant electrode through the wall of the basal turn of the cochlea - a report on two patients. AB - We describe the unusual complication of the cochlear implant electrode eroding through the lateral bony wall of the cochlear basal turn in 2 different patients. This complication, occurring during life, has not been previously described in the literature. Radiological investigations were vital in making this diagnosis. We also discuss the likely pathophysiology behind this complication. PMID- 17854101 TI - Ligand-activated lithium-mediated zincation of N-phenylpyrrole. AB - Metalation of N-phenylpyrrole by using an in situ mixture of ZnCl(2)TMEDA (0.5 equiv; TMEDA=N,N,N',N'-tetramethylethylenediamine) and LiTMP (1.5 equiv; TMP=2,2,6,6-tetramethylpiperidino) was optimized. The reaction carried out at room temperature in THF resulted in incomplete metalation (56 % conversion) and selectivity (mixture of 2-iodo and 2,2'-diiodo derivatives in an 86:14 ratio after trapping with iodine). By using diethyl ether (DEE), toluene, or hexane instead of THF, low conversions of 17, 38, or 23 % were observed, respectively, but the formation of the diiodide was avoided. When hexane was used as solvent, strong lithium-complexing ligands such as [12]crown-4 and N,N' dimethylpropylideneurea (DMPU) inhibited the reaction whereas more (hemi)labile ligands (TMEDA>THF approximately DME) favored it. This result shows that a temporary accessibility of lithium to interact with the rest of the base and/or the substrate is a prerequisite for an efficient metalation. A 75 % yield of 2 iodo-N-phenylpyrrole was obtained after reaction with the base in the presence of five equivalents of TMEDA for two hours at room temperature, and subsequent trapping with iodine. We were able to successfully replace the spare TMP with a less expensive butyl group. PMID- 17854102 TI - Non-cytotoxic, bifunctional EuIII and TbIII luminescent macrocyclic complexes for luminescence resonant energy-transfer experiments. AB - A new macrocyclic ligand, L3, has been synthesised, based on the cyclen framework grafted with three phenacyl light-harvesting groups and a C5-alkyl chain bearing a carboxylic acid function as a potential linker for biological material. Acidity constants are determined by spectrophotometric titrations, as well as conditional stability constants for the resulting 1:1 complexes with trivalent lanthanide ions. The complexes have stabilities comparable to 1,4,7,10 tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane (dtma) complexes, with pLn approximately 12-13. Photophysical properties of the ligand and of the EuL3 and TbL3 complexes have been determined for both microcrystalline samples and solutions in water and acetonitrile. They point to the metal ion being present in an environment with axial symmetry derived from the C4 point group. The hydration number determined for TbL3 decreases with increasing pH value and becomes fractional at pH 7.5, which points to an equilibrium between two differently solvated species and probably to the participation of the deprotonated carboxylic acid chain in the complexation. The quantum yields in water (1.9% for EuIII, 3.4% for TbIII) are smaller than those for complexes with the symmetrically substituted parent macrocycle, but efficient luminescence resonant energy transfer (LRET) was observed when Cy5 dye was added to the solutions. Finally, the influence of the TbL3 complex on cell viability is tested on both malignant (5D10 mouse hybridoma, Jurkat human T leukaemia, MCF-7 human breast carcinoma) and non-malignant (Hacat human keratinocyte) cell lines. Cell viability after 24 h incubation at 37 degrees C with 500 microM TbL3 was >90% for all cell lines, except Jurkat (>70%). All of these properties make LnL3 complexes interesting potential probes for bioanalyses. PMID- 17854103 TI - Peri- and enantioselectivity of thermal, scandium-, and [pybox/scandium] catalyzed Diels-Alder and hetero-Diels-Alder reactions of methyl (E)-2-oxo-4-aryl butenoates with cyclopentadiene. AB - The cycloaddition between methyl (E)-2-oxo-4-aryl-3-butenoates (2 a-d) and cyclopentadiene, in addition to the expected normal Diels-Alder (DA) adducts endo 3 a-d and exo-4 a-d, gives the less expected endo-5 a-d products of the [4+2] hetero-Diels-Alder (HDA) reaction in which the alpha-ketoester behaves as a heterodiene. If a comparison is made between the thermal and the scandium(III) triflate-catalyzed conditions, the periselectivity changes and whereas under thermal conditions the main products are those from the DA reaction (3 a-d), in the presence of Sc(OTf)3 (OTf=triflate), the HDA products 5 a-d become largely predominant. The reactions are enantioselectively catalyzed by the scandium(III) triflate complex of (4'S,5'S)-2,6-bis[4'-(triisopropylsilyl)oxymethyl-5'-phenyl 1',3'-oxazolin-2'-yl]pyridine (1) and both the DA and the HDA products are obtained with excellent enantiomeric excess, up to >99% ee. The X-ray crystallographic structure determination of 5 c assigns it the 4R,4aS,7aR absolute configuration. The thermal retro-Claisen rearrangement of 3 c into (4R,4aS,7aR)-5 c allows the correlation of their absolute configuration, and 3 c has therefore the 2R,3R configuration. By analogy the same absolute configuration can be assigned to 3 a,b,d and 5 a,b,d, and the stereospecific thermal Claisen rearrangement of the optically active 5 a,b,d into 3 a,b,d completes the correlation between their absolute configuration. The [3,3]-sigmatropic rearrangements can be easily carried out under catalytic conditions with scandium(III) triflate, which promotes the equilibration between 3 a-d and 5 a-d, with a different degree of enantioselectivity characterizing the process starting from 3 a-d or 5 a-d. The unambiguous attributions of the configuration to the products allows us to propose a rationale of the stereochemical outcome of the catalyzed cycloaddition and to investigate the reaction mechanism of the competing DA and HDA reactions and shifts in products distribution by acid catalysis. PMID- 17854104 TI - One-pot three-component catalytic synthesis of fully substituted pyrroles from readily available propargylic alcohols, 1,3-dicarbonyl compounds and primary amines. AB - A simple and highly efficient method for the preparation of fully substituted pyrroles, from readily accessible secondary propargylic alcohols, 1,3-dicarbonyl compounds and primary amines, has been developed. The one-pot multicomponent reaction, which is catalysed by the system [Ru(eta(3)-2 C(3)H(4)Me)(CO)(dppf)][SbF(6)]/CF(3)CO(2)H (dppf: 1,1' bis(diphenylphosphanyl)ferrocene), involves initial propargylation of the 1,3 dicarbonyl compound promoted by CF(3)CO(2)H and subsequent condensation between the resulting gamma-keto alkyne and the primary amine to afford a propargylated beta-enamino ester or ketone, which undergoes a ruthenium-catalysed 5-exo-dig annulation to form the final pyrrole. PMID- 17854105 TI - Ubiquitin stability and the Lys63-linked polyubiquitination site are compromised on copper binding. PMID- 17854106 TI - Ion mobility-mass spectrometry reveals long-lived, unfolded intermediates in the dissociation of protein complexes. PMID- 17854107 TI - Single-molecule reactions in liposomes. PMID- 17854108 TI - Chemical speciation by selective heteronuclear single-quantum coherence spectroscopy: determination of double-bond quantity in unsaturated fatty acid compounds. AB - A method for identifying fatty acid species based on the number of double bonds contained in a lipid molecule is presented. Common to all polyunsaturated fatty acids are two signature resonances at approximately 5.3 and 2.8 ppm in the proton chemical-shift spectrum of NMR. These resonances are from the vinyl and bis-allyl protons, respectively, and, although they can be readily observed by NMR from lipid extracts of biological samples, direct speciation has never been demonstrated by NMR. By modifying a conventional HSQC pulse sequence with a J pulse on the spin system of the vinyl group (generalized as an IS spin system) at the beginning of the initial polarization transfer period and selectively inverting the 13C (I) spins with a narrowband sech/tanh inversion pulse, the collection of data in both dimensions can be restricted to a narrow slice of the chemical-shift range. The resolution is subsequently determined by digitizer efficiency, and spectra can be collected optimally from within a very narrow 1 x 6 ppm window of the respective proton and carbon chemical-shift ranges. With this modification it is possible to distinguish at least one resonance each from the multiple shifts expected from the indirectly detected nuclei of the fatty acid species, oleic acid, linoleic acid, linolenic acid and arachidonic acid, which contain one, two, three and four double bonds, respectively. This and similar methods of applied selectivity are of potential interest in characterizing speciation in biological samples where mixtures are often encountered and chemical shifts of the same structural group of similar molecules give rise to complicated overlapping resonances but are important for diagnosis of disease processes such as cancer. PMID- 17854109 TI - An efficient, facile, and general stereoselective synthesis of heterosubstituted alkylidenecyclopropanes. PMID- 17854110 TI - Protecting-group-free formal synthesis of platensimycin. PMID- 17854111 TI - Combined experimental and theoretical study on the nature and the metastable decay pathways of the amino acid ion fragment [M-H]-. PMID- 17854112 TI - Clay mimics color tuning in visual pigments. PMID- 17854113 TI - Effect of collagen turnover and matrix metalloproteinase activity on healing of venous leg ulcers. AB - BACKGROUND: The presence of fibrous tissue in poorly healing venous leg ulcers suggests abnormal collagen metabolism. The aim was to determine whether there were differences in collagen turnover and matrix metalloproteinase (MMP) activity between ulcers that healed, those that did not heal and normal skin. METHODS: Biopsies were taken from the ulcers of 12 patients whose venous ulcers went on to heal and 15 patients whose ulcers failed to heal despite 12 months of compression bandaging. Biopsies were taken from 15 normal controls. Collagen turnover (collagen III N-terminal propeptide (PIIINP) and degraded collagen), and total MMP, MMP-1 and MMP-3 activities were measured. RESULTS: PIIINP and degraded collagen levels were higher in ulcers that healed compared with lesions that failed to heal (P = 0.005 and P < 0.001 respectively) and normal skin (P = 0.003 and P < 0.001). MMP-1 activity was also higher in healing ulcers than resistant ulcers (P < 0.001) and normal skin (P < 0.001). Significantly more total MMP activity was present in all ulcers than in normal skin (P < 0.001), but there was no difference in total MMP (and MMP-3 activity) between ulcers that healed and those that did not. CONCLUSION: Rapidly healing venous leg ulcers had increased collagen turnover and MMP-1 activity, which appeared to differentiate them from those that failed to heal within 12 months. PMID- 17854114 TI - Clinicopathological significance of fibrous tissue around fixed recurrent rectal cancer in the pelvis. AB - BACKGROUND: Fibrous tissue around a locally recurrent rectal tumour is an interesting histological feature, but its clinicopathological significance has not been investigated. METHODS: This retrospective study examined clinicopathological findings in 48 patients who underwent curative total pelvic exenteration with distal sacrectomy (TPES) between 1992 and 2004. Data were analysed with respect to fibrosis around the recurrent tumour, categorized into one of three groups: no fibrosis (f0), partial fibrosis (f1) or circumferential fibrosis (f2). RESULTS: Ten, 17 and 21 patients had f0, f1 and f2 fibrosis respectively, with 5-year survival of none, four and eight patients respectively. The overall survival of patients with circumferential fibrosis was significantly better than that in patients with no fibrosis (P = 0.003). Univariable analysis showed that a high level of sacrectomy (P = 0.036), absence of lymphatic invasion (P = 0.031) and circumferential fibrosis (P = 0.039) were significantly associated with better overall survival. In multivariable analysis, circumferential fibrosis (P = 0.031) and low serum carcinoembryonic antigen levels (P = 0.044) were independent factors for a favourable outcome. CONCLUSION: The outcome of patients with locally recurrent rectal cancer after curative TPES appears to be better when circumferential fibrosis is present around the tumour. PMID- 17854115 TI - Use of SDS micelles for improving sensitivity, resolution, and speed in the analysis of beta-lactam antibiotics in environmental waters by SPE and CE. AB - This study dealt with the potential of MEKC with LIF detection involving derivatization with sulfoindocyanine succinimidyl ester (Cy5) for the separation and determination of beta-lactam antibiotics (ampicillin, amoxicillin, cephradine, and cephalexin) in environmental water samples. Water samples of 50 mL were enriched by SPE by passage through a weak base-cation Amberlite(R) IRA-93 exchange column. SDS micelles play important roles in the whole analytical process by improving the yield (sensitivity) and the kinetics of the labeling reaction, the elution of the retained antibiotics from the SPE preconcentration system and the electrophoretic resolution of their Cy5-derivatives. The optimum procedure includes a derivatization step of the antibiotics at 25 degrees C for 10 min and direct injection for MEKC analysis, which is conducted within about 15 min using 15 mM SDS in the running buffer (35 mM sodium borate at pH 9.3). LODs from 30 to 45 ng/L and RSDs (within-day precision) from 3.5 to 5.9% were obtained for the antibiotics in water samples with average recoveries ranging from 96.4 to 99.4%. These results indicate that the method proposed is a straightforward and sensitive tool for the determination of these antibiotics in environmental water samples providing similar quantitative results to those using more expensive equipment like LC-electrospray MS/MS. PMID- 17854116 TI - A new electrochemiluminescent detection system equipped with an electrically heated carbon paste electrode for CE. AB - An electrochemiluminescent (ECL) detection system in CE with an electrically heated carbon paste electrode (CPE) was developed. This CPE could be heated by a 100 kHz alternating current (ac) generated from a function generator, and the temperature of the electrode (Te) could be controlled. To evaluate the feasibility and reliability of this system, the electrochemically generated Ru(bpy)(3) (3+)-based ECL reaction was used for detection of triethylamine (TEA) and tri-n-propylamine (TPrA). Ru(bpy)(3) (2+) was added into the separation buffer solution with precolumn mode. Effects of several important factors were investigated to acquire the optimum conditions. Under the optimum conditions, the heated electrode has been shown to provide advantages by the measurement of ECL intensity in CE at elevated Te. Compared with the conventional electrode at the room temperature, using heated CPE could improve peak shape and gain good reproducibility with lower detection limits and wider linearity ranges. Compared with the room temperature, the linear ranges and detection limits (S/N = 3) for TEA and TPrA were improved about one magnitude when the Te was 39 degrees C. In contrast, the RSD was lower than for the electrode at room temperature. PMID- 17854119 TI - Mass distribution, polydispersity, and focusing properties of carrier ampholytes for IEF. Part V: pH 9-11 interval. AB - As a last part of an investigation on all 2-pH-unit intervals of carrier ampholytes (CAs) for IEF (see Electrophoresis 2006, 27, 3919-3934; 2006, 27, 4849 4858; 2007, 28, 715-723) two different lots of Servalyt CAs, in the pH 9-11 range, have been analyzed by a 2-D technique based on preparative Rotofor fractionation followed by capillary electrophoresis mass-spectrometry of 10 out of 20 fractions harvested, in the second dimension. The findings: the two lots contain 65 and 69 different M(r) compounds, in the M(r) interval of 232-667 Da, for a total of 341-387 isoforms, respectively. Since this is a chaotic organic synthesis, the high reproducibility (here demonstrated for the first time during the 40 years of existence of CAs) of the synthetic process (for two batches produced at 6 years of distance) is remarkable, considering that a 94% agreement for the individual chemicals and 88% agreement for the total number of isoforms for the two lots is found. It is additionally demonstrated that the lower pI species are accompanied by considerably more isoforms than the high pI forms and that in all cases such isoforms consist of family of compounds clustered around the pI of the parental form, with a pI spread of ca. 0.1-0.2 pH units. PMID- 17854120 TI - A novel sodium bis(2-ethylhexyl) sulfosuccinate-PAGE system suitable for the separation of small peptides. AB - A novel sodium bis(2-ethylhexyl) sulfosuccinate-PAGE (AOT-PAGE) system which delivers high resolution and sensitivity for small peptides with molecular masses of 0.8-17 kDa is described. Small peptides migrate more slowly and are less prone to leakage than in conventional SDS-PAGE, thus allowing for the in-gel detection with CBB R 250 of 0.5 mug of peptide. The system is also compatible with electroblotting, activity staining in renatured gels, and the peptide analysis by MALDI-MS. AOT-PAGE is simpler, more rapid, and cheaper than the generally adopted Tricine-SDS-PAGE method. PMID- 17854121 TI - DNA conformation and base number simultaneously determined in a nanopore. AB - When dsDNA polymers containing identical number of base pairs were electrophoresed through a nanopore in a voltage biased silicon nitride membrane, the measured time integral of blocked ionic current (the event-charge-deficit, ecd, Fologea, D., Gershow, M., Ledden, B., McNabb, D. S. et al.., Nano Lett. 2005, 5, 1905-1909) for each translocation event was the same regardless of whether the molecules were in a linear, circular relaxed, or supercoiled form. Conversely, when DNA polymers containing different numbers of base pairs were electrophoresed through a nanopore, the ecd depended strongly on, and predicted the value of, the molecule's number of base pairs. Measurements showed that the magnitude of the current blockages was strongly affected by a molecule's form. The current blockages exhibited characteristic differences that distinguished among single-stranded linear, double-stranded linear, circular relaxed, and supercoiled forms. Because the data that establish ecd are usually determined concomitantly with current blockade measurements, our results show that a single nanopore assay can simultaneously determine both DNA conformation and base number. PMID- 17854122 TI - An investigation of peak-broadening effects arising when combining CE with MS. AB - In this study, peak-broadening effects caused by nebulizing gas flow and lack of temperature control have been investigated for separation capillaries with three different inner diameters. The study was performed with serial UV/ESI-MS detection in an effort to distinguish between peak broadening arising in the separation and peak broadening arising in the ion source. The nebulizing gas was found to significantly affect both migration time and separation efficiency when using capillaries with 50 and 75 microm id. If the nebulizing gas is on during injection, the injection volume increases to such an extent that significant peak broadening is induced. Reducing the id to 25 microm minimizes the parabolic flow induced by the nebulizing gas. Results indicate that the nebulizing gas pressure can be optimized to minimize peak broadening in the ion source. A decrease in detection sensitivity, possibly related to the orthogonal design of the interface, was observed when the nebulizing gas pressure was increased. A tapered capillary tip was found to provide superior separation efficiency as well as sensitivity. PMID- 17854123 TI - Computer simulation of different modes of ACE based on the dynamic complexation model. AB - Several modes of the often used ACE processes are simulated based on the principle of dynamic complexation of interacting species in a capillary column. The model is built on the mass transfer equation, to provide insight into the detailed analyte migration and interaction processes in CE. Normal ACE, Hummel Dreyer method, vacancy affinity CE, vacancy peak method, and CE frontal analysis are simulated based on typical ACE conditions, and the results are compared with the detector responses of real CE processes using BSA and warfarin as a model system. Remarkable resemblance between the simulated results and the experimental observations was demonstrated for well-buffered ACE systems. PMID- 17854124 TI - Determination of peptide hormones of brain and intestine by CE with ESI-MS detection. AB - A new method for the determination of the peptide hormones of brain and intestine based on CE coupling with a DAD and ESI-MS was established. Several electrophoretic and ESI-MS parameters were investigated in detail, such as electrolyte nature and concentration, organic solvent and sheath liquid compositions, nebulization gas pressure and the ESI capillary voltage. Optimized conditions were achieved with 25 mM formic acid-ammonium formate (pH 2.9) as the optimal electrolyte, 2 mM formic acid in 80% methanol in water as the sheath liquid, and 20 kV applied voltage. Under the optimized conditions, four protonated peptides were separated by CE and selectively detected by a quadrupole mass spectrometer with a sheath flow ESI interface. LODs for the four peptides (neurotensin hexapeptide, neurotensin, cholecystokinin tetrapeptide, and pentagastrin) were in the range of 0.10-0.60 micromol/L at an S/N of 3. The RSDs (n = 8) of the method were 0.70-1.5% for migration times and 1.6-6.1% for peak areas. This method is simple, rapid, and selective compared with RIA and ELISA techniques, and has been applied to the analysis of rat hypothalamus tissue. PMID- 17854125 TI - Bulk modification of PDMS microchips by an amphiphilic copolymer. AB - A simple and rapid bulk-modification method based on adding an amphiphilic copolymer during the fabrication process was employed to modify PDMS microchips. Poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) was used as the additive substance. Compared to the native PDMS microchips, both the contact angle and the EOF of the bulk-modified PDMS microchips decreased. The effects of the additive loading and the pH on the EOF were investigated in detail. The bulk-modified PDMS microchips exhibited reproducible and stable EOF behavior. The application of the bulk-modified PDMS microchips was also studied and the results indicated that they could be successfully used to separate amino acids and to suppress protein adsorption. PMID- 17854126 TI - Novel staining-free proteomic method for simultaneous identification of proteins and determination of their pI values by using low-molecular-mass pI markers. AB - A new proteomic staining-free method for simultaneous identification of proteins and determination of their pI values by using low-molecular-mass pI markers is described. It is based on separation of proteins in gels by IEF in combination with mass spectrometric analysis of both peptides derived by in-gel digestion and low-molecular-mass pI markers extracted form the same piece excised from the gel. In this method, the pI markers are mixed with a protein mixture (a commercial malted barley protein extract) deposited on a gel and separated in a pH gradient. Color pI markers enable supervision of progress of focusing process. Several separated bands of the pI markers (including separated proteins) were excised and the pI markers were eluted from each gel piece by water/ethanol and identified by MALDI-TOF/TOF MS. The remaining carrier ampholytes were then washed out from gel pieces and proteins were in-gel digested with trypsin or chymotrypsin. Obtained peptides were measured by MALDI-TOF/TOF MS and proteins were identified via protein database search. This procedure allows omitting time-consuming protein staining and destaining procedures, which shortens the analysis time. For comparison, other IEF gels were stained with CBB R 250 and proteins in the gel bands were identified. Similarity of the results confirmed that our approach can give information about the correct pI values of particular proteins in complex samples at significantly shorter analysis times. This method can be very useful for identification of proteins and their post-translational modifications in prefractioned samples, where post-translational modifications (e.g., glycation) are frequent. PMID- 17854127 TI - Lights, Camera, Action! systematic variation in 2-D difference gel electrophoresis images. AB - 2-D Difference gel electrophoresis (DIGE) circumvents many of the problems associated with gel comparison via the traditional 2-DE approach. DIGE's accuracy and precision, however, is compromised by the existence of other significant sources of systematic variation, including that caused by the apparatus used for imaging proteins (location of the camera and lighting units, background material, imperfections within that material, etc.). Through a series of experiments, we estimate some of these factors, and account for their effect on the DIGE experimental data, thus providing improved estimates of the true relative protein intensities. The model presented here includes 2-DE images as a special case. PMID- 17854131 TI - From bed to bench: which attitude towards the laboratory liver tests should health care practitioners strike? AB - There is a general consensus in re-interpreting the so-called liver function tests in the light of novel discoveries. At the same time, recent evidence favours the use of different laboratory data to assess liver damage, fibrosis or regenerative process, but this point is not always shared. Actually, balancing the need for diagnosis, prognostic evaluation and therapy response of liver disease with a good cost/benefit ratio is very difficult. New tests are probably not needed but the aim should be for better utilization of existing tests to contain the increasing cost of health care. PMID- 17854133 TI - Role of alcohol in the regulation of iron metabolism. AB - Patients with alcoholic liver disease frequently exhibit increased body iron stores, as reflected by elevated serum iron indices (transferrin saturation, ferritin) and hepatic iron concentration. Even mild to moderate alcohol consumption has been shown to increase the prevalence of iron overload. Moreover, increased hepatic iron content is associated with greater mortality from alcoholic cirrhosis, suggesting a pathogenic role for iron in alcoholic liver disease. Alcohol increases the severity of disease in patients with genetic hemochromatosis, an iron overload disorder common in the Caucasian population. Both iron and alcohol individually cause oxidative stress and lipid peroxidation, which culminates in liver injury. Despite these observations, the underlying mechanisms of iron accumulation and the source of the excess iron observed in alcoholic liver disease remain unclear. Over the last decade, several novel iron regulatory proteins have been identified and these have greatly enhanced our understanding of iron metabolism. For example, hepcidin, a circulatory antimicrobial peptide synthesized by the hepatocytes of the liver is now known to play a central role in the regulation of iron homeostasis. This review attempts to describe the interaction of alcohol and iron-regulatory molecules. Understanding these molecular mechanisms is of considerable clinical importance because both alcoholic liver disease and genetic hemochromatosis are common diseases, in which alcohol and iron appear to act synergistically to cause liver injury. PMID- 17854134 TI - Implication of altered proteasome function in alcoholic liver injury. AB - The proteasome is a major protein-degrading enzyme, which catalyzes degradation of oxidized and aged proteins, signal transduction factors and cleaves peptides for antigen presentation. Proteasome exists in the equilibrium of 26S and 20S particles. Proteasome function is altered by ethanol metabolism, depending on oxidative stress levels: low oxidative stress induces proteasome activity, while high oxidative stress reduces it. The proposed mechanisms for modulation of proteasome activity are related to oxidative modification of proteasomal proteins with primary and secondary products derived from ethanol oxidation. Decreased proteolysis by the proteasome results in the accumulation of insoluble protein aggregates, which cannot be degraded by proteasome and which further inhibit proteasome function. Mallory bodies, a common signature of alcoholic liver diseases, are formed by liver cells, when proteasome is unable to remove cytokeratins. Proteasome inhibition by ethanol also promotes the accumulation of pro-apoptotic factors in mitochondria of ethanol-metabolizing liver cells that are normally degraded by proteasome. In addition, decreased proteasome function also induces accumulation of the negative regulators of cytokine signaling (I kappaB and SOCS), thereby blocking cytokine signal transduction. Finally, ethanol elicited blockade of interferon type 1 and 2 signaling and decreased proteasome function impairs generation of peptides for MHC class I-restricted antigen presentation. PMID- 17854136 TI - Role of transmethylation reactions in alcoholic liver disease. AB - Alcoholic liver disease is a major health care problem worldwide. Findings from many laboratories, including ours, have demonstrated that ethanol feeding impairs several of the many steps involved in methionine metabolism. Ethanol consumption predominantly results in a decrease in the hepatocyte level of S adenosylmethionine and the increases in two toxic metabolites, homocysteine and S adenosylhomocysteine. These changes, in turn, result in serious functional consequences which include decreases in essential methylation reactions via inhibition of various methyltransferases. Of particular interest to our laboratory is the inhibition of three important enzymes, phosphatidylethanolamine methyltransferase, isoprenylcysteine carboxyl methyltransferase and protein L isoaspartate methyltransferase. Decreased activity of these enzymes results in increased fat deposition, increased apoptosis and increased accumulation of damaged proteins-all of which are hallmark features of alcoholic liver injury. Of all the therapeutic modalities available, betaine has been shown to be the safest, least expensive and most effective in attenuating ethanol-induced liver injury. Betaine, by virtue of aiding in the remethylation of homocysteine, removes both toxic metabolites (homocysteine and S-adenosylhomocysteine), restores S-adenosylmethionine level, and reverses steatosis, apoptosis and damaged proteins accumulation. In conclusion, betaine appears to be a promising therapeutic agent in relieving the methylation and other defects associated with alcoholic abuse. PMID- 17854137 TI - Effects of ethanol on hepatic cellular replication and cell cycle progression. AB - Ethanol is a hepatotoxin. It appears that the liver is the target of ethanol induced toxicity primarily because it is the major site of ethanol metabolism. Metabolism of ethanol results in a number of biochemical changes that are thought to mediate the toxicity associated with ethanol abuse. These include the production of acetaldehyde and reactive oxygen species, as well as an accumulation of nicotinamide adenine dinucleotide (NADH). These biochemical changes are associated with the accumulation of fat and mitochondrial dysfunction in the liver. If these changes are severe enough they can themselves cause hepatotoxicity, or they can sensitize the liver to more severe damage by other hepatotoxins. Whether liver damage is the result of ethanol metabolism or some other hepatotoxin, recovery of the liver from damage requires replacement of cells that have been destroyed. It is now apparent that ethanol metabolism not only causes hepatotoxicity but also impairs the replication of normal hepatocytes. This impairment has been shown to occur at both the G1/S, and the G2/M transitions of the cell cycle. These impairments may be the result of activation of the checkpoint kinases, which can mediate cell cycle arrest at both of these transitions. Conversely, because ethanol metabolism results in a number of biochemical changes, there may be a number of mechanisms by which ethanol metabolism impairs cellular replication. It is the goal of this article to review the mechanisms by which ethanol metabolism mediates impairment of hepatic replication. PMID- 17854135 TI - Immunological response in alcoholic liver disease. AB - The development of alcoholic liver disease (ALD) can be attributed to many factors that cause damage to the liver and alter its functions. Data collected over the last 30 years strongly suggests that an immune component may be involved in the onset of this disease. This is best evidenced by the detection of circulating autoantibodies, infiltration of immune cells in the liver, and the detection of hepatic aldehyde modified proteins in patients with ALD. Experimentally, there are numerous immune responses that occur when proteins are modified with the metabolites of ethanol. These products are formed in response to the high oxidative state of the liver during ethanol metabolism, causing the release of many inflammatory processes and potential of necrosis or apoptosis of liver cells. Should cellular proteins become modified with these reactive alcohol metabolites and be recognized by the immune system, then immune responses may be initiated. Therefore, it was the purpose of this article to shed some insight into how the immune system is involved in the development and/or progression of ALD. PMID- 17854138 TI - Effect of ethanol on pro-apoptotic mechanisms in polarized hepatic cells. AB - Chronic ethanol consumption is associated with serious and potentially fatal alcohol-related liver injuries such as hepatomegaly, alcoholic hepatitis and cirrhosis. Moreover, it has been documented that the clinical progression of alcohol-induced liver damage may be associated with an increase in hepatocellular death that involves apoptotic mechanisms. Although much information has been learned about the clinical manifestations associated with alcohol-related diseases, the search continues for a better understanding of the molecular and/or cellular mechanisms by which ethanol exerts its deleterious effects such as the induction of pro-apoptotic mechanisms and related cell damaging events. As part of the effort to enhance our understanding of those particular cellular pathways and mechanisms associated with ethanol toxicity, researchers over the years have utilized a variety of model systems. Recently, work has come forth demonstrating the utility of a hybrid cell line (WIF-B) as a cell culture model system for the study of alcohol-associated alterations in hepatocellular mechanisms. Success with such emerging model systems could aid in the development of potential therapeutic treatments for the prevention of alcohol-induced apoptotic cell death that may ultimately serve as a significant target in delaying the onset and/or progression of clinical symptoms of alcohol-mediated liver disease. This review article summarizes the current understanding of ethanol-mediated modifications in cell survival and thus the promotion of pro-apoptotic events with emphasis on analyses made in various experimental model systems, particularly the more recently characterized WIF-B cell system. PMID- 17854139 TI - Novel interactions of mitochondria and reactive oxygen/nitrogen species in alcohol mediated liver disease. AB - Mitochondrial dysfunction is known to be a contributing factor to a number of diseases including chronic alcohol induced liver injury. While there is a detailed understanding of the metabolic pathways and proteins of the liver mitochondrion, little is known regarding how changes in the mitochondrial proteome may contribute to the development of hepatic pathologies. Emerging evidence indicates that reactive oxygen and nitrogen species disrupt mitochondrial function through post-translational modifications to the mitochondrial proteome. Indeed, various new affinity labeling reagents are available to test the hypothesis that post-translational modification of proteins by reactive species contributes to mitochondrial dysfunction and alcoholic fatty liver disease. Specialized proteomic techniques are also now available, which allow for identification of defects in the assembly of multi-protein complexes in mitochondria and the resolution of the highly hydrophobic proteins of the inner membrane. In this review knowledge gained from the study of changes to the mitochondrial proteome in alcoholic hepatotoxicity will be described and placed into a mechanistic framework to increase understanding of the role of mitochondrial dysfunction in liver disease. PMID- 17854140 TI - Alcohol-induced steatosis in liver cells. AB - Alcohol-induced fatty liver (steatosis) was believed to result from excessive generation of reducing equivalents from ethanol metabolism, thereby enhancing fat accumulation. Recent findings have revealed a more complex picture in which ethanol oxidation is still required, but specific transcription as well as humoral factors also have important roles. Transcription factors involved include the sterol regulatory element binding protein 1 (SREBP-1) which is activated to induce genes that regulate lipid biosynthesis. Conversely, ethanol consumption causes a general down-regulation of lipid (fatty acid) oxidation, a reflection of inactivation of the peroxisome proliferator-activated receptor-alpha (PPAR-alpha) that regulates genes involved in fatty acid oxidation. A third transcription factor is the early growth response-1 (Egr-1), which is strongly induced prior to the onset of steatosis. The activities of all these factors are governed by that of the principal regulatory enzyme, AMP kinase. Important humoral factors, including adiponectin, and tumor necrosis factor-alpha (TNF-alpha), also regulate alcohol-induced steatosis. Their levels are affected by alcohol consumption and by each other. This review will summarize the actions of these proteins in ethanol-elicited fatty liver. Because steatosis is now regarded as a significant risk factor for advanced liver pathology, an understanding of the molecular mechanisms in its etiology is essential for development of effective therapies. PMID- 17854141 TI - Signaling mechanisms in alcoholic liver injury: role of transcription factors, kinases and heat shock proteins. AB - Alcoholic liver injury comprises of interactions of various intracellular signaling events in the liver. Innate immune responses in the resident Kupffer cells of the liver, oxidative stress-induced activation of hepatocytes, fibrotic events in liver stellate cells and activation of liver sinusoidal endothelial cells all contribute to alcoholic liver injury. The signaling mechanisms associated with alcoholic liver injury vary based on the cell type involved and the extent of alcohol consumption. In this review we will elucidate the oxidative stress and signaling pathways affected by alcohol in hepatocytes and Kupffer cells in the liver by alcohol. The toll-like receptors and their down-stream signaling events that play an important role in alcohol-induced inflammation will be discussed. Alcohol-induced alterations of various intracellular transcription factors such as NFkappaB, PPARs and AP-1, as well as MAPK kinases in hepatocytes and macrophages leading to induction of target genes that contribute to liver injury will be reviewed. Finally, we will discuss the significance of heat shock proteins as chaperones and their functional regulation in the liver that could provide new mechanistic insights into the contributions of stress-induced signaling mechanisms in alcoholic liver injury. PMID- 17854142 TI - Nerve growth factor involvement in liver cirrhosis and hepatocellular carcinoma. AB - AIM: To define NGF (nerve growth factor) and its high-affinity receptor trkA(NGF) presence and distribution in fibrotic liver and in HCC, and to verify if NGF might have a role in fibrosis and HCC. METHODS: Intracellular distribution of NGF and trkA(NGF) were assessed by immunohistochemistry and immuno-electron microscopy in liver specimens from HCC, cirrhosis or both. ELISA was used to measure circulating NGF levels. RESULTS: NGF and trkA(NGF) were highly expressed in HCC tissue, mainly localized in hepatocytes, endothelial and some Kupffer cells. In the cirrhotic part of the liver they were also markedly expressed in bile ducts epithelial and spindle-shaped cells. Surprisingly, in cirrhotic tissue from patients without HCC, both NGF and trkA(NGF) were negative. NGF serum levels in cirrhotic and/or HCC patient were up to 25-fold higher than in controls. CONCLUSION: NGF was only detected in liver tissue with HCC present. Intracellular distribution suggests paracrine and autocrine mechanisms of action. Better definition of mechanisms may allow for therapeutic and diagnostic/prognostic use of NGF. PMID- 17854143 TI - Correlation of IL-8 with induction, progression and metastatic potential of colorectal cancer. AB - AIM: To investigate the expression profile of IL-8 in inflammatory and malignant colorectal diseases to evaluate its potential role in the regulation of colorectal cancer (CRC) and the development of colorectal liver metastases (CRLM). METHODS: IL-8 expression was assessed by quantitative real-time PCR (Q-RT PCR) and the enzyme-linked immunosorbent assay (ELISA) in resected specimens from patients with ulcerative colitis (UC, n = 6) colorectal adenomas (CRA, n = 8), different stages of colorectal cancer (n = 48) as well as synchronous and metachronous CRLM along with their corresponding primary colorectal tumors (n = 16). RESULTS: IL-8 mRNA and protein expression was significantly up-regulated in all pathological colorectal entities investigated compared with the corresponding neighboring tissues. However, in the CRC specimens IL-8 revealed a significantly more pronounced overexpression in relation to the CRA and UC tissues with an average 30-fold IL-8 protein up-regulation in the CRC specimens in comparison to the CRA tissues. Moreover, IL-8 expression revealed a close correlation with tumor grading. Most interestingly, IL-8 up-regulation was most enhanced in synchronous and metachronous CRLM, if compared with the corresponding primary CRC tissues. Herein, an up to 80-fold IL-8 overexpression in individual metachronous metastases compared to normal tumor neighbor tissues was found. CONCLUSION: Our results strongly suggest an association between IL-8 expression, induction and progression of colorectal carcinoma and the development of colorectal liver metastases. PMID- 17854144 TI - Protective effects of ursodeoxycholic acid on chenodeoxycholic acid-induced liver injury in hamsters. AB - AIM: To investigate the effects of ursodeoxycholic acid (UDCA) on chenodeoxycholic acid (CDCA)-induced liver injury in hamsters, and to elucidate a correlation between liver injury and bile acid profiles in the liver. METHODS: Liver injury was induced in hamsters by administration of 0.5% (w/w) CDCA in their feed for 7 d. UDCA (50 mg/kg and 150 mg/kg) was administered for the last 3 d of the experiment. RESULTS: At the end of the experiment, serum alanine aminotransferase (ALT) increased more than 10 times and the presence of liver injury was confirmed histologically. Marked increase in bile acids was observed in the liver. The amount of total bile acids increased approximately three-fold and was accompanied by the increase in hydrophobic bile acids, CDCA and lithocholic acid (LCA). UDCA (50 mg/kg and 150 mg/kg) improved liver histology, with a significant decrease (679.3 +/- 77.5 U/L vs 333.6 +/- 50.4 U/L and 254.3 +/- 35.5 U/L, respectively, P < 0.01) in serum ALT level. UDCA decreased the concentrations of the hydrophobic bile acids, and as a result, a decrease in the total bile acid level in the liver was achieved. CONCLUSION: The results show that UDCA improves oral CDCA-induced liver damage in hamsters. The protective effects of UDCA appear to result from a decrease in the concentration of hydrophobic bile acids, CDCA and LCA, which accumulate and show the cytotoxicity in the liver. PMID- 17854145 TI - Liver angiogenesis as a risk factor for hepatocellular carcinoma development in hepatitis C virus cirrhotic patients. AB - AIM: To evaluate the predictive value of hepatocyte proliferation and hepatic angiogenesis for the occurrence of Hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) cirrhotic patients. METHODS: One hundred-five patients (69 males, 36 females; age range, 51-90 year; median 66 year) with biopsy proven HCV cirrhosis were prospectively monitored for HCC occurrence for a median time of 64 mo. Angiogenesis was assessed by using microvessel density (MVD), hepatocyte turnover by MIB1 and PCNA indexes at inclusion in liver biopsies. RESULTS: Forty six patients (43.8%) developed HCC after a median time of 55 (6-120) mo while 59 (56.2%) did not. Patients were divided into two groups according to the median value of each index. The difference between patients with low (median MVD = 3; range 0-20) and high (median MVD = 7; range 1-24) MVD was statistically significant (chi(2) = 22.06; P < 0.0001) which was not the case for MIB1 or PCNA (MIB-1: chi(2) = 1.41; P = 0.2351; PCNA: chi(2) = 1.27; P = 0.2589). The median MVD was higher in patients who developed HCC than in those who did not. HCC-free interval was significantly longer in patients with the MVD < or = 4 (P = 0.0006). No relationship was found between MIB1 or PCNA and MVD (MIB-1 r(2) = 0.00007116, P = 0.9281; PCNA: r(2) = 0.001950; P = 0.6692). MVD only was able to predict the occurrence of HCC in these patients. Among other known risk factors for HCC, only male sex was statistically associated with an increased risk. CONCLUSION: Liver angiogenesis has a role for in HCV-related liver carcinogenesis and for defining patients at higher risk. PMID- 17854146 TI - Coinfection of hepatitis B and hepatitis C virus in HIV-infected patients in south India. AB - AIM: To screen for the co-infection of hepatitis B (HBV) and hepatitis C virus (HCV) in human immunodeficiency virus (HIV) infected patients in southern India. METHODS: Five hundred consecutive HIV infected patients were screened for Hepatitis B Virus (HBsAg and HBV-DNA) and Hepatitis C virus (anti-HCV and HCV RNA) using commercially available ELISA kits; HBsAg, HBeAg/anti-HBe (Biorad laboratories, USA) and anti-HCV (Murex Diagnostics, UK). The HBV-DNA PCR was performed to detect the surface antigen region (pre S-S). HCV-RNA was detected by RT-PCR for the detection of the constant 5' putative non-coding region of HCV. RESULTS: HBV co-infection was detected in 45/500 (9%) patients and HCV co infection in 11/500 (2.2%) subjects. Among the 45 co-infected patients only 40 patients could be studied, where the detection rates of HBe was 55% (22/40), antiHBe was 45% (18/40) and HBV-DNA was 56% (23/40). Among 11 HCV co-infected subjects, 6 (54.5%) were anti-HCV and HCV RNA positive, while 3 (27.2%) were positive for anti-HCV alone and 2 (18%) were positive for HCV RNA alone. CONCLUSION: Since the principal routes for HIV transmission are similar to that followed by the hepatotropic viruses, as a consequence, infections with HBV and HCV are expected in HIV infected patients. Therefore, it would be advisable to screen for these viruses in all the HIV infected individuals and their sexual partners at the earliest. PMID- 17854147 TI - Three novel missense germline mutations in different exons of MSH6 gene in Chinese hereditary non-polyposis colorectal cancer families. AB - AIM: To investigate the germline mutations of MSH6 gene in probands of Chinese hereditary non-polyposis colorectal cancer (HNPCC) families fulfilling different clinical criteria. METHODS: Germline mutations of MSH6 gene were detected by PCR based DNA sequencing in 39 unrelated HNPCC probands fulfilling different clinical criteria in which MSH2 and MLH1 mutations were excluded. To further investigate the pathological effects of detected missense mutations, we analyzed the above related MSH6 exons using PCR-based sequencing in 137 healthy persons with no family history. The clinicopathological features were collected from the Archive Library of Cancer Hospital, Fudan University and analyzed. RESULTS: Four germline missense mutations distributed in the 4(th), 6(th) and 9(th) exons were observed. Of them, three were not found in international HNPCC databases and did not occur in 137 healthy controls, indicating that they were novel missense mutations. The remaining mutation which is consistent with the case H14 at c.3488A>T of exon 6 of MSH6 gene was also found in the controls, the rate was approximately 3.65% (5/137) and the type of mutation was not found in the international HNPCC mutational and SNP databases, suggesting that this missense mutation was a new SNP unreported up to date. CONCLUSION: Three novel missense mutations and a new SNP observed in the probands of Chinese HNPCC families, may play an important role in the development of HNPCC. PMID- 17854148 TI - (18)F-DG PET/CT in detection of recurrence and metastasis of colorectal cancer. AB - AIM: To evaluate the value of (18)F-DG PET/CT in detecting recurrence and/or metastasis of colorectal cancer (CRC). METHODS: Combined visual analysis with semiquantitative analysis, the (18)F-DG PET/CT whole-body imaging results and the corresponding clinical data of 68 postoperative CRC patients including 48 male and 20 female with average age of 58.1 were analyzed retrospectively. RESULTS: Recurrence and/or metastasis were confirmed in 56 patients in the clinical follow up after the PET/CT imaging. The sensitivity of PET/CT diagnosis of CRC recurrence and/or metastasis was 94.6%, and the specificity was 83.3%. The positive predictive value (PPV) was 96.4% and the negative predictive value (NPV) was 76.9%. PET/CT imaging detected one or more occult malignant lesions in 8 cases where abdominal/pelvic CT and/or ultrasonography showed negative findings, and also detected more lesions than CT or ultrasonography did in 30.4% (17/56) cases. Recurrence and/or metastasis was detected in 91.7% (22/24) cases with elevated serum CEA levels by (18)F-DG PET/CT imaging. CONCLUSION: (18)F-DG PET/CT could detect the recurrence and/or metastasis of CRC with high sensitivity and specificity. PMID- 17854149 TI - Thymidylate synthase and thymidine phosphorylase gene expression as predictive parameters for the efficacy of 5-fluorouracil-based adjuvant chemotherapy for gastric cancer. AB - AIM: To investigate the prognostic role of thymidylate synthase (TS) and thymidine phosphorylase (TP) mRNA levels in T3 or T4 gastric cancer treated with 5-fluorouracil-based adjuvant chemotherapy. METHODS: Fifty-one patients with T3 or T4 gastric cancer received systemic 5-fluorouracil-based adjuvant chemotherapy, and intratumoral expression of TS and TP in 51 gastric cancer tissue samples was tested by real-time quantitative PCR. RESULTS: The median disease-free survival (DFS) time was 10.2 mo in the patients. There were no significant differences in DFS between the groups with high and low levels of TP. However, the group with low level of TS had a longer DFS (14.4 mo vs 8.3 mo, P = 0.017). The median overall survival (OS) time was 18.5 mo, and there were significant differences in OS between the groups with high and low levels of TS or TP (for TS, 17.0 mo vs 21.3 mo, P = 0.010; for TP, 16.6 mo vs 22.5 mo, P = 0.009). Moreover, the coupled low expression of these two genes was strongly associated with a longer survival time of patients as compared with that of a single gene. CONCLUSION: Expression of TS and TP mRNA is a useful predictive parameter for the survival of postoperative gastric cancer patients after 5 fluorouracil-based adjuvant chemotherapy. PMID- 17854150 TI - Laparoscopic hemicolectomy in a patient with situs inversus totalis. AB - As among persons with normal anatomy, occasional patients with situs inversus develop malignant tumors. Recently, several laparoscopic operations have been reported in patients with situs inversus. We describe laparoscopic hemicolectomy with radical lymphadenectomy in such a patient. Careful consideration of the mirror-image anatomy permitted safe operation using techniques not otherwise differing from those in ordinary cases. Thus, curative laparoscopic surgery for colon cancer in the presence of situs inversus is feasible and safe. PMID- 17854152 TI - Glucosinolate concentration in turnip (Brassica rapa ssp. rapifera L.) roots as affected by nitrogen and sulfur supply. AB - Three greenhouse pot experiments were conducted with four different nitrogen (N) treatments (80, 160, 240, and 320 kg ha (-1)) in combination with three sulfur (S) treatments (10, 20, and 60 kg ha (-1)) to study the effects of combined N and S supply on glucosinolate concentration and composition in turnip roots. Total glucosinolate concentration varied widely from 9.7 (N 320S 10) to 91.6 (N 160S 60) mg (100 g) (-1) root fresh weight (FW) and individual glucosinolate concentrations were increased with increasing S supply regardless of the N treatment, whereas enhanced N supply (160 - 320 N ha (-1)) at the high S level (60 kg ha (-1)) did not affect total glucosinolate concentration. In contrast, assumingly attributed to the individual glucosinolate biosynthesis concentration of N-containing tryptophan-derived indole glucosinolate was highest with increased N supply, whereas S-containing methionine-derived aromatic and aliphatic glucosinolates decreased with increasing N supply combined at low S level (10-20 kg ha (-1)). PMID- 17854151 TI - Novel online sensor technology for continuous monitoring of milk coagulation and whey separation in cheesemaking. AB - The cheese industry has continually sought a robust method to monitor milk coagulation. Measurement of whey separation is also critical to control cheese moisture content, which affects quality. The objective of this study was to demonstrate that an online optical sensor detecting light backscatter in a vat could be applied to monitor both coagulation and syneresis during cheesemaking. A prototype sensor having a large field of view (LFV) relative to curd particle size was constructed. Temperature, cutting time, and calcium chloride addition were varied to evaluate the response of the sensor over a wide range of coagulation and syneresis rates. The LFV sensor response was related to casein micelle aggregation and curd firming during coagulation and to changes in curd moisture and whey fat contents during syneresis. The LFV sensor has potential as an online, continuous sensor technology for monitoring both coagulation and syneresis during cheesemaking. PMID- 17854153 TI - Brunneins A-C, beta-carboline alkaloids from Cortinarius brunneus. AB - Four beta-carboline alkaloids, brunneins A-C (1-3) and 3-(7-hydroxy-9H-beta carboline-1-yl)propanoic acid (4), were isolated from fruiting bodies of the agaricoid fungus Cortinarius brunneus. The structures of 1-3 were determined by analysis of NMR and MS data, and the structure of compound 4 was determined by comparison with published data. Brunnein A (1) exhibited very low cholinesterase inhibitory effects and no cytotoxicity. PMID- 17854154 TI - Bioactive p-terphenyl derivatives from a Cordyceps-colonizing isolate of Gliocladium sp. AB - Gliocladinins A (1) and B (2), two new p-terphenyl derivatives, have been isolated from solid cultures of an isolate of Gliocladium sp. that colonizes Cordyceps sinensis. The structures of these compounds were determined mainly by analysis of their NMR spectroscopic data. In standard disk assays, compounds 1 and 2 showed modest antimicrobial activity against Staphylococcus aureus (ATCC 6538). In addition, these compounds displayed inhibitory effects on the growth of two human tumor cell lines, HeLa and HCT116. PMID- 17854155 TI - Cyclopentenone prostaglandin, 15-deoxy-Delta12,14-PGJ2, is metabolized by HepG2 cells via conjugation with glutathione. AB - 15-deoxy-Delta12,14-prostaglandin J2 (15-d-PGJ2) is a dehydration product of PGD2. This compound possesses a highly reactive polyunsaturated carbonyl moiety that is a substrate for Michael addition with thiol-containing biomolecules such as glutathione and cysteine residues on proteins. By reacting with glutathione and proteins, 15-d-PGJ2 is believed to exert potent biological activity. Despite the large number of publications that have ascribed bioactivity to this molecule, it is not known to what extent 15-d-PGJ2 is formed in vivo. Levels of free 15-d PGJ2 measured in human biological fluids such as urine are low, and the biological importance of this compound has thus been questioned. Because of its reactivity, we hypothesized that 15-d-PGJ2 is present in vivo primarily as a Michael conjugate. Therefore, we undertook a detailed study of the metabolism of this compound in HepG2 cells that are known to metabolize other cyclopentenone eicosanoids. We report that HepG2 cells primarily convert 15-d-PGJ2 to a glutathione conjugate in which the carbonyl at C-11 is reduced to a hydroxyl. Subsequently, the glutathione portion of the molecule is hydrolyzed with loss of glutamic acid and glycine resulting in a cysteine conjugate. These findings confirm a general route for the metabolism of cyclopentenone eicosanoids in HepG2 cells and may pave the way for new insights regarding the formation of 15-d-PGJ2 in vivo. PMID- 17854156 TI - Fast, sensitive, and inexpensive alternative to analytical pigment HPLC: quantification of chlorophylls and carotenoids in crude extracts by fitting with Gauss peak spectra. AB - Quantification of pigments in complex mixtures is an important task in the physiology of photosynthetic organisms, because pigment composition differs depending on the species, tissue, and physiological state. Currently available methods, however, are either limited to very few pigments (classical UV/vis spectroscopic methods), or they are time-consuming, labor intensive, or costly (e.g., HPLC). Here we describe a UV/vis spectrophotometric method that is capable of a rapid (approximately 1 min/sample) and inexpensive (<1 euro/sample) quantification of more than a dozen pigments in a crude extract, which means it is suitable for high-throughput screening applications. A detection limit of <1 pmol for each pigment allows for determining the pigment composition in only 0.5 microg of lyophilized leaves or algae. The method is based on the description of each pigment spectrum by a series of Gaussian peaks. A sample spectrum is then fitted by a linear combination of these "Gauss peak spectra" including an automatic correction of wavelength inaccuracy, baseline instability, sample turbidity, and effects of temperature/water content. Here we present the Gauss peak spectra from 350 to 750 nm for acetone solutions of all chlorophyll and carotenoid derivatives that are abundant (including conditions of Cd, Cu, or Zn stress) in leaves of higher plants, Euglena, brown algae, and various cyanobacteria like Anabaena and Trichodesmium: [Mg]-Chl a, b, c1, c2; pheophytin a, b; [Cd]-Chl a, b; [Cu]-Chl a, b; [Zn]-Chl a, b; antheraxanthin, aurochrome, beta-carotene, beta-cryptoxanthin, cis- and trans-canthaxanthin, diadinochrome (=diadinoxanthin 5,6-epoxide), cis- and trans-diadinoxanthin, diatoxanthin, cis- and trans-echinenone, fucoxanthin, lutein, myxoxanthophyll, neoxanthin, violaxanthin, and all three stereoisomers of zeaxanthin in acetone. We present extensive tests of our new quantification method for determining optimal and limiting conditions of its performance and for comparison with previous methods. Finally, we show application examples for Thlaspi fendleri (Chlorophyta), Euglena gracilisc (Euglenophyta), Ectocarpus siliculosus (Phaeophyta), and Trichodesmium erythraeum IMS101 (cyanobacteria). PMID- 17854157 TI - Microimmunoanalysis on standard compact discs to determine low abundant compounds. AB - High-density competitive indirect microimmunoassays were performed in both sides of compact discs by direct absorption of immunoreagents on polycarbonate surface, using gold- or enzyme-labeled immunoglobulins as tracers for displaying the immunoreaction. The operational principle is based on the use of a low reflectivity compact disc as analytical platform that allows the reflection/transmission (30/70%) of the CD reader laser beam (lambda 780 nm). The reflected light is used to scan the disc track keeping it in movement. The transmitted light is detected by a planar photodiode integrated on the CD drive. The variation of the optical transmission of the light caused by the immunoreaction products is related to the sample concentration. As a proof of concept, low abundant compounds, commonly used as pesticides, were detected in a 60-min total assay time, with a limit of detection ranging from 0.02 to 0.62 microg/L for 2,4,5-TP, chlorpyriphos, and metolachlor. The obtained results show the enormous prospective of compact discs in combination with CD players for multiresidue and drug discovery applications. PMID- 17854158 TI - Use of a designed peptide array to infer dissociation trends for nontryptic peptides in quadrupole ion trap and quadrupole time-of-flight mass spectrometry. AB - Observed peptide gas-phase fragmentation patterns are a complex function of many variables. To systematically probe this phenomenon, an array of 40 peptides was synthesized for study. The array of sequences was designed to hold certain variables (peptide length) constant and randomize or balance others (peptide amino acid distribution and position). A high-quality tandem mass spectrometry (MS/MS) data set was acquired for each peptide for all observed charge states on multiple MS instruments, quadrupole-time-of-flight and quadrupole ion trap. The data were analyzed as a function of total charge state and number of mobile protons. Previously known dissociation trends were observed, validating our approach. In addition, the general influence of basic amino acids on dissociation could be determined because, in contrast to the more widely studied tryptic peptides, the amino acids H, K, and R were positionally distributed. Interestingly, our results suggest that cleavage at all basic amino acids is suppressed when a mobile proton is available. Cleavage at H becomes favored only under conditions where a partially mobile proton is present, a caveat to the previously reported trend of enhanced cleavage at H. Finally, all acquired data were used as a benchmark to determine how well these sequences would have been identified in a database search using a common algorithm, Mascot. PMID- 17854159 TI - Multivariate statistical analysis of three-spatial-dimension TOF-SIMS raw data sets. AB - Three-spatial-dimension (3D) time-of-flight-secondary ion mass spectrometry (TOF SIMS) analysis can be performed if an X-Y image is saved at each depth of a depth profile. In this paper, we will show how images reconstructed from specified depths, depth profiles generated from specific X-Y coordinates, as well as three spatial-dimensional rendering provide for a better understanding of the sample than traditional depth profiling where only a single spectrum is collected at each depth. We will also demonstrate, for the first time, that multivariate statistical analysis (MVSA) tools can be used to perform a rapid, unbiased analysis of the entire 3D data set. In the example shown here, retrospective analysis and MVSA revealed a more complete picture of the 3D chemical distribution of the sample than did the as-measured depth profiling alone. Color overlays of the MVSA components as well as animated movies allowing for visualization (in 3D) from various angles will be provided. PMID- 17854160 TI - Coupling of sequential injection chromatography with multivariate curve resolution-alternating least-squares for enhancement of peak capacity. AB - Flow-through low-pressure chromatographic separations capitalized on the sequential injection chromatographic (SIC) concept are for the first time coupled to second-order multivariate regression models based on multivariate curve resolution-alternating least-squares (MCR-ALS) for outperforming current chromatographic methods in terms of resolution efficiency. The proposed SIC-MCR ALS method involving sequential injection separation on short monolithic columns along with isocratic elution fosters ultrafast reversed-phase separations of complex multicomponent mixtures regardless of peak overlapping and retention parameters. The ruggedness of SIC systems is enhanced by removing the solenoid valves from the flow network, thus diminishing the column back pressure effects. As a consequence, the flow setup admitted mobile-phase flow rates much higher than those traditionally enabled in SIC. To ascertain the improved peak capacity of the SIC-MCR-ALS procedure, five phenolic species commonly used in disinfectant products and featuring similar UV spectra and close retention times in short reversed-phase silica-based monolithic phases are selected as model compounds and determined in just 1 min using mobile-phase flow rates of >or=2 mL min(-1). Notwithstanding the fact that the five phenolic derivatives coelute in a single chromatographic band, thus rendering resolution values ranging from 0.05 to 1.11, the concentration profiles and the pure spectra of each individual phenol species could be concurrently obtained. Quantitative validation of the chromatographic chemometric method demonstrated both the reliability of the results and the enhanced resolution of mixtures with regard to former SIC systems with no need for thorough optimization of the separation conditions. PMID- 17854161 TI - Performance, resolving power, and radial ion distributions of a prototype nanoelectrospray ionization resistive glass atmospheric pressure ion mobility spectrometer. AB - In this article, we describe and characterize a novel ion mobility spectrometer constructed with monolithic resistive glass desolvation and drift regions. This instrument is equipped with switchable corona discharge and nanoelectrospray ionization sources and a Faraday plate detector. Following description of the instrument, pulsing electronics, and data acquisition system, we examine the effects of drift gas flow rate and temperature, and of the aperture grid to anode distance on the observed resolving power and sensitivity. Once optimum experimental parameters are identified, different ion gate pulse lengths, and their effect on the temporal spread of the ion packet were investigated. Resolving power ranged from an average value of 50 ms/ms for a 400-micros ion gate pulse, up to an average value of 68 ms/ms for a 100-micros ion gate pulse, and a 26-cm drift tube operated at 383 V cm(-1). Following these experiments, the radial distribution of ions in the drift region of the spectrometer was studied by using anodes of varying sizes, showing that the highest ionic density was located at the center of the drift tube. Finally, we demonstrate the applicability of this instrument to the study of small molecules of environmental relevance by analyzing a commercially available siderophore, deferoxamine mesylate, in both the free ligand and Fe-bound forms. Ion mobility experiments showed a dramatic shift to shorter drift times caused by conformational changes upon metal binding, in agreement with previous reversed-phase liquid chromatography observations. PMID- 17854162 TI - Quenching of I(2P1/2) by NO2, N2O4, and N2O. AB - Quenching of excited iodine atoms (I(5p5, 2P1/2)) by nitrogen oxides are processes of relevance to discharge-driven oxygen iodine lasers. Rate constants at ambient and elevated temperatures (293-380 K) for quenching of I(2P1/2) atoms by NO2, N2O4, and N2O have been measured using time-resolved I(2P1/2) --> I(2P3/2) 1315 nm emission. The excited atoms were generated by pulsed laser photodissociation of CF3I at 248 nm. The rate constants for I(2P1/2) quenching by NO2 and N2O were found to be independent of temperature over the range examined with average values of (2.9 +/- 0.3) x 10(-15) and (1.4 +/- 0.1) x 10(-15) cm3 s( 1), respectively. The rate constant for quenching of I(2P1/2) by N2O4 was found to be (3.5 +/- 0.5) x 10(-13) cm3 s(-1) at ambient temperature. PMID- 17854163 TI - Noble gas anions: a theoretical investigation of FNgBN- (Ng = He-Xe). AB - Noble gas anions of general formula FNgBN- (Ng = He-Xe) have been investigated by MP2, coupled-cluster, and multireference-CI calculations with correlation consistent basis sets. These species reside in deep wells on the singlet potential energy surface and are thermodynamically stable with respect to the loss of F, F-, BN, and BN-. They are unstable with respect to Ng + FBN-, but at least for Ng = Ar, Kr, and Xe, the involved energy barriers are high enough to suggest their conceivable existence as metastable species. The stability of FNgBN arises from the strong F--stabilization of the elusive NgBN. The character of the boron-noble gas bond passes from purely ionic for FHeBN- and FNeBN- to covalent for FXeBN-. PMID- 17854164 TI - Cooperativity between OH...O and CH...O hydrogen bonds involving dimethyl sulfoxide-H2O-H2O complex. AB - The cooperativity between the O-H...O and C-H...O hydrogen bonds has been studied by quantum chemical calculations at the MP2/6-311++G(d,p) level in gaseous phase and at the B3LYP/6-311++G(d,p) level in solution. The interaction energies of the O-H...O and C-H...O H-bonds are increased by 53 and 58%, respectively, demonstrating that there is a large cooperativity. Analysis of hydrogen-bonding lengths, OH bond lengths, and OH stretching frequencies also supports such a conclusion. By NBO analysis, it is found that orbital interaction plays a great role in enhancing their cooperativity. The strength increase of the C-H...O H bond is larger than that of the O-H...O H-bond due to the cooperativity. The solvent has a weakening effect on the cooperativity. PMID- 17854166 TI - Heterotricyclic himbacine analogs as potent, orally active thrombin receptor (protease activated receptor-1) antagonists. AB - Pursuing our earlier efforts in the himbacine-based thrombin receptor antagonist area, we have synthesized a series of compounds that incorporate heteroatoms in the C-ring of the tricyclic motif. This effort has resulted in the identification of several potent heterocyclic analogs with excellent affinity for the thrombin receptor. Several of these compounds demonstrated robust inhibition of platelet aggregation in an ex vivo model in cynomolgus monkeys following oral administration. A detailed profile of 28b, a benchmark compound in this series, with a Ki of 4.3 nM, is presented. PMID- 17854167 TI - Ligand-based virtual screening by novelty detection with self-organizing maps. AB - We describe a novel method for ligand-based virtual screening, based on utilizing Self-Organizing Maps (SOM) as a novelty detection device. Novelty detection (or one-class classification) refers to the attempt of identifying patterns that do not belong to the space covered by a given data set. In ligand-based virtual screening, chemical structures perceived as novel lie outside the known activity space and can therefore be discarded from further investigation. In this context, the concept of "novel structure" refers to a compound, which is unlikely to share the activity of the query structures. Compounds not perceived as "novel" are suspected to share the activity of the query structures. Nowadays, various databases contain active structures but access to compounds which have been found to be inactive in a biological assay is limited. This work addresses this problem via novelty detection, which does not require proven inactive compounds. The structures are described by spatial autocorrelation functions weighted by atomic physicochemical properties. Different methods for selecting a subset of targets from a larger set are discussed. A comparison with similarity search based on Daylight fingerprints followed by data fusion is presented. The two methods complement each other to a large extent. In a retrospective screening of the WOMBAT database novelty detection with SOM gave enrichment factors between 105 and 462-an improvement over the similarity search based on Daylight fingerprints between 25% and 100%, when the 100 top ranked structures were considered. Novelty detection with SOM is applicable (1) to improve the retrieval of potentially active compounds also in concert with other virtual screening methods; (2) as a library design tool for discarding a large number of compounds, which are unlikely to possess a given biological activity; and (3) for selecting a small number of potentially active compounds from a large data set. PMID- 17854168 TI - Rates of electronic excitation hopping in anisotropic ionic crystals of [Ru(2,2' bipyridine)3]X2 (X = ClO4-, PF6-, SbF6-); Monte Carlo simulation of single- and multi-exponential emission decays. AB - Emission decays of triplet metal-to-ligand charge transfer states in anisotropic crystals of [Ru(1 - x)Os(x)(bpy)(3)]X(2) (bpy = 2,2'-bipyridine, X = PF(6)-, ClO(4)-, SbF(6)-, and 0.115 > x > 0.001) at approximately 300 K were measured by means of time-correlated single-photon counting. Rates of excitation hopping calculated on the basis of an interaction between transition dipoles of a donor cation and an acceptor cation are insufficient to simulate the single-exponential decays (x = 0.0099) and the multiexponential decays (x = 0.060 and 0.115) of the PF(6)- salt crystals. A limiting rate of excitation hopping to an imaginary cation at the van der Waals distance via a super-exchange interaction between d orbitals through the bpy ligands was determined to be 0.83 x 10(10) s(-1) on average by means of a step-by-step Monte Carlo simulation, assuming an distance attenuation factor, beta, of the exchange interaction of 10 nm-1. The total rate of excitation hopping via both a dipole-dipole mechanism and a super-exchange mechanism to the neighboring sites of the cation was calculated to be 5.4 x 10(9) s(-1) for the PF(6)- crystal. Anisotropic diffusion constants estimated from the hopping rates and lengths in the PF(6)- crystal are 9.3 x 10(-6), 9.1 x 10(-6), and 1.4 x 10(-6) cm(2)s(-1) along the a axis, the b axis, and the c axis, respectively, which are compared with an isotropic diffusion constant, 1.3 x 10( 6) cm(2) s(-1), estimated from the pseudo-bimolecular rate constant of excitation transfer to [Os(bpy)(3)](2+), using an isotropic Smoluchowski equation. A multiexponential emission decay of [Ru(0.885)Os(0.115)(bpy)(3)](PF(6))(2) was also simulated to determined the limiting rate of excitation transfer to [Os(bpy)(3)](2+) at the van der Waals distance (2.6 x 10(11) s(-1)). The magnitude of beta determined is 6.5 and 11.5 nm(-1) for the ClO(4)- and the SbF(6)- salt crystals, respectively, on reference to that of beta (10 nm(-1)) for the PF(6)- salt crystal. PMID- 17854169 TI - A novel bis tridentate bipyridine carboxamide ligand and its complexation to copper(II): synthesis, structure, and magnetism. AB - A new bis tridentate ligand 2,2'-bipyridine-3,3'-[2-pyridinecarboxamide] H(2)L(1) which can bind transition metal ions has been synthesized via the condensation of 3,3'-diamino-2,2'-bipyridine together with 2-pyridine carbonyl chloride. Two copper(II) coordination compounds have been prepared and characterized: [Cu(2)(L(1))(hfac)(2)].3CH(3)CN.H(2)O (1) and [Cu(2)(L(1))Cl(2)].CH(3)CN (2). The single-crystal X-ray structures reveal that complex 1 crystallizes in the triclinic space group P1, with the unit cell parameters a = 12.7185(6) A, b = 17.3792(9) A, c = 19.4696(8) A, alpha = 110.827(2) degrees, beta = 99.890(3) degrees, gamma = 97.966(3) degrees, V = 3868.3(3) A3, Z = 4, R = 0.0321 and R(w) = 0.0826. Complex 2 crystallizes in the monoclinic space group P2(1)/n with the unit cell parameters a = 12.8622(12) A, b = 9.6100(10) A, c = 19.897(2) A, beta = 102.027(3) degrees, V = 2405.3(4) A(3), Z = 4, R = 0.0409 and R(w) = 0.1005. In both complexes the ligand is in the dianionic form and coordinates the divalent Cu(II) ions via one amido and two pyridine nitrogen donor atoms. In 1, the coordination geometry around both Cu(II) ions is best described as distorted trigonal bipyramidal where the remaining two coordination sites are satisfied by hexafluoroacetylacetonate counterions. In 2 both Cu(II )ions adopt a (4 + 1) distorted square pyramidal geometry. One copper forms a longer apical bond to an adjacent carbonyl oxygen atom, whereas the second copper is chelated to a neighboring Cu-Cl chloride ion to afford a mu-Cl-bridged dimerized [Cu(2)(L(1))Cl(2)](2) complex. The magnetic susceptibility data for 1 (2 -270 K), reveal the occurrence of weak antiferromagnetic interactions between the Cu(II) ions. In contrast, variable-temperature magnetic susceptibility measurements for 2 reveal more complex magnetic properties, with the presence of a weak antiferromagnetic exchange (J = -10.1 K) between the copper ions in each dinuclear copper complex and a stronger ferromagnetic exchange interaction (J = 32.9 K) between the Cu(II) ions of the Cu(mu-Cl)(2)Cu dimeric bridging units. PMID- 17854170 TI - Structurally homologous beta- and meso-alkynyl amidinium porphyrins. AB - Alkynylamidinium groups have been introduced at the beta and meso positions of a nickel(II) porphyrin (PNi(II)) framework. The modification permits the distance between the amidinium-amidine acid-base group and porphyrin to be increased while effectively maintaining pi conjugation between the porphyrin macrocycle and the acid-base functionality. Use of an ethynyl spacer as a linker (i) extends the amidinium functionality away from the sterically bulky mesityl groups of the porphyrin, allowing it to be nearly planar with respect to the porphyrin ring, and (ii) draws the pi-orbital character of the porphyrin out toward the amidinium functionality, thereby engendering sensitivity of the electronic properties of the porphyrin macrocycle to the protonation state of the amidinium. The barrier for rotation of the amidinium group, as calculated by time-dependent density functional theory (TDDFT), is approximately 8.5 kT (5 kcal/mol) for both porphyrins. Analysis of UV-visible absorption profiles for the beta- and meso alkynylamidinium PNi(II) upon deprotonation enables accurate determination of the amidinium acidity constants for the ground state (pK(a)(beta) = 7.03 +/- 0.1, pK(a)(meso) = 7.74 +/- 0.1 in CH(3)CN) and excited state (pK(a)*(beta) = 6.89 +/- 0.1, pK(a)*(meso) = 8.37 +/- 0.1 in CH(3)CN) porphyrins. Whereas pK(a)* < pK(a) for the beta-alkynylamidinium porphyrin, pK(a)* > pK(a) for the meso alkynylamidinium porphyrin, indicating that beta-alkynylamidinium PNi(II) is a photoacid and meso-alkynylamidinium PNi(II) is a photobase. These divergent behaviors are supported by analysis of the frontier molecular orbitals of the homologous pair with TDDFT. PMID- 17854171 TI - Use of drug discovery tools in rational organometallic catalyst design. AB - A computational procedure is detailed where techniques common in the drug discovery process-2D- and 3D-quantitative structure-activity relationships (QSAR) are applied to rationalize the catalytic activity of a synthetically flexible, Ti N=P ethylene polymerization catalyst system. Once models relating molecular properties to catalyst activity are built with the two QSAR approaches, two database mining approaches are used to select a small number of ligands from a larger database that are likely to produce catalysts with high activity when grafted onto the Ti-N=P framework. The software employed throughout this work is freely available, is easy to use, and was applied in a "black box" approach to highlight areas where the drug discovery tools, designed to address organic molecules, have difficulty in addressing issues arising from the presence of a metal atom. In general, 3D-QSAR offers an efficient way to screen new potential ligands and separate those likely to lead to poor catalysts from those that are likely to contribute to highly active catalysts. The results for 2D-QSAR appear to be quantitatively unreliable, likely due to the presence of a metal atom; nonetheless, there is evidence that qualitative predictions from different models may be reliable. Pitfalls in the database mining techniques are identified, none of which are insurmountable. The lessons learned about the potential uses and drawbacks of the techniques described herein are readily applicable to other catalyst frameworks, thereby enabling a rational approach to catalyst improvement and design. PMID- 17854172 TI - Two coordination polymers created via in situ ligand synthesis involving C-N and C-C bond formation. AB - We report the synthesis and crystal structures of two transition metal-based coordination polymers comprising ligand molecules not included in the original reaction mixtures but instead formed in situ during hydrothermal treatment. Zinc meso-iminodisuccinate hydrate (I), Zn(2)(C(8)H(7)NO(8)).0.57H(2)O, formed from zinc acetate and L-aspartic acid, and tetraaquanickel(II) 5,10-dioxo-5,10-dihydro 4,9-dioxa-pyrene-2,7-dicarboxylate (II), Ni(H(2)O)(4)(C(16)H(4)O(8)), formed from nickel acetate and 5-hydroxyisophthalic acid. We show that the formation of I takes place via a fumaric acid intermediate, while the formation of II requires the formation of a new C-C bond. The structure of I consists of weakly interacting sheets, while the structure of II consists of strongly hydrogen bonded chains. Crystal data: for I, P2(1)/n (14), a = 10.073 A, b = 9.894 A, c = 12.053 A, beta = 105.605 degrees, V = 1156.87(13) A(3), Z = 4; for II, P1 (2), a = 5.011 A, b = 6.526 A, c = 12.305 A, alpha = 76.868 degrees, beta = 84.988 degrees, gamma = 87.619 degrees, V = 390.3(4) A(3), Z = 1. PMID- 17854173 TI - Synthesis, structure, and unexpected magnetic properties of La3Re2O10. AB - The compound La(3)Re(2)O(10) has been synthesized by solid-state reaction and characterized by powder neutron diffraction, SQUID magnetometry, and heat capacity measurements. Its structure consists of isolated [Re(2)O(10)](9-) dimer units of two edge-shared ReO(6) octahedra, separated by La(3+) within the lattice. The Re-Re distance within the dimer units is 2.488 A, which is indicative of metal-metal bonding with a bond order of 1.5. The average oxidation state of the Re atom is +5.5, leaving one unpaired electron per dimer unit (S = 1/2). Although the closest interdimer distance is 5.561 A, the magnetic susceptibility data and heat capacity measurements indicate this compound exhibits both short- and long-range magnetic order at surprisingly high temperatures. The zero field cooled (ZFC) magnetic susceptibility data show two broad features at 55 and 105 K, indicating short-range order, and a sharper cusp at 18 K, which signifies long-range antiferromagnetic order. The heat capacity of La(3)Re(2)O(10) shows a lambda-type anomaly at 18 K, which is characteristic of long-range magnetic order. DFT calculations determined that the unpaired electron resides in a pi-bonding orbital and that the unpaired electron density is widely delocalized over the atoms within the dimer, with high values at the bridging oxygens. Extended Huckel spin dimer calculations suggest possible interaction pathways between these dimer units within the crystal lattice. Results from the calculations and fits to the susceptibility data indicate that the short-range magnetic ordering may consist of 1-D antiferromagnetic linear chains of coupled S = 1/2 dimers. The magnetic structure of the antiferromagnetic ground state could not be determined by unpolarized neutron powder diffraction. PMID- 17854174 TI - Anion-solvent dependence of bistability in a family of meridional N-donor-ligand containing iron(II) spin crossover complexes. AB - Five mononuclear spin crossover iron(II) bis-meridional ligand complexes of the general formula [Fe(L)(2)](X)(2).solvent, have been synthesized, where X = BF(4)- or ClO(4)-; L = 2-(1-pyridin-2-ylmethyl-1H-pyrazol-3-yl)-pyrazine (picpzpz) or 2 (3-(2-pyridyl)pyrazol-1-ylmethyl)pyridine) (picpypz); solvent = MeOH or EtOH. The magnetic and structural consequences of systematic variation of meridional ligand, solvent, and anion, including a desolvated species, have been investigated. The complex [Fe(picpzpz)(2)](BF(4))(2).MeOH, 1.MeOH, displays several unique properties including a two-step spin transition with a gradual higher-temperature step ((1)T(1/2) = 197 K) and an abrupt low-temperature step with hysteresis ((2)T(1/2) = 91/98 K) and a metastable intermediate spin state below 70 K with quench-cooling. Removal of the solvent methanol results in the loss of the abrupt step and associated hysteresis (T(1/2) = 150 K). The complexes [Fe(picpzpz)(2)](BF(4))(2).EtOH (1.EtOH), [Fe(picpzpz)(2)](ClO(4))(2).MeOH (2.MeOH), [Fe(picpzpz)(2)](ClO(4))(2).EtOH (2.EtOH), and [Fe(picpypz)(2)](BF(4))(2).MeOH (3.MeOH) all show gradual one-step spin transitions with T(1/2) values in the range 210-250 K. Photomagnetic LIESST measurements on 1.MeOH reveal a near-quantitative excitation of high-spin sites and a unique two-step relaxation process related to the two-step thermal spin transition ((1)T(LIESST) = 49 K and (2)T(LIESST) = 70 K). The structural consequences of the unusual spin transition displayed by 1.MeOH have been investigated by single-crystal X-ray diffraction structural analyses between 25 and 293 K. Detailed characterization of the unit cell parameter evolution vs temperature reflects both the gradual high-temperature step and abrupt low temperature step, including the thermal hysteresis, observed magnetically. PMID- 17854175 TI - Three-dimensional 3d-4f polymers containing heterometallic rings: syntheses, structures, and magnetic properties. AB - Two novel three-dimensional (3D) 3d-4f mixed complexes [Ln(H(2)O)(4)][Ni(2)TTHA(SCN)(2)].H(3)O+ [Ln = Pr (1), Ce (2); H(6)TTHA = triethylenetetraaminehexaacetic acid], based on the building blocks of [Ni(2)TTHA(SCN)(2)](4-), were synthesized and characterized by X-ray crystal diffraction and magnetic properties. The single-crystal structures show that these complexes form a 3D framework, comprised of an unusual infinite one dimensional chain based on heterometallic Ln2Ni2 rings. The temperature-dependent magnetic susceptibilities were analyzed by an approximate model, leading to g = 2.06. Delta = 2.83, zJ' = -0.6 cm-1 for complex 1 and g = 2.07, Delta = 1.00, zJ' = -0.5 cm(-1) for complex 2. PMID- 17854176 TI - Magnetic properties of bulk BiCrO3 studied with dc and ac magnetization and specific heat. AB - Single-phased powder BiCrO(3) sample was prepared at 6 GPa and 1653 K. Its magnetic properties were investigated by dc/ac magnetization, magnetic relaxation, and specific heat measurements. Four anomalies of magnetic origin were found near 40, 75, 109, and 111 K. The long-range antiferromagnetic order with weak ferromagnetism occurs at T(N) = 109 K. The ac susceptibilities showed that the transition near T(N) is a two-step transition. Additional frequency independent broad anomalies were observed on the real part of the ac susceptibilities near 75 K, likely, caused by the change in the magnetic easy axis. The dc magnetic susceptibilities also had anomalies at 75 K, and the isothermal magnetization curves and relaxation curves changed their behavior below 75 K. Below 40 K, frequency-dependent anomalies with very large temperature shifts were observed on both the real and imaginary parts of the ac susceptibilities. The monoclinic-to-orthorhombic structural phase transition near 420 K was investigated by magnetization and differential scanning calorimetry measurements. PMID- 17854177 TI - Syntheses of mono- and dinuclear diiodoboryl complexes of platinum. AB - Treatment of [Pt(PCy(3))(2)] (Cy = cyclohexyl) with BI(3) afforded trans [(Cy(3)P)(2)Pt(I)(BI(2))] by the oxidative addition of a B-I bond. The title compound represents the first diiodoboryl complex and was fully characterized by NMR spectroscopy and X-ray diffraction analysis. The latter revealed a very short Pt-B distance, thus indicating a pronounced pi contribution to this bond. By the addition of another 1 equiv of BI(3) to trans-[(Cy(3)P)(2)Pt(I)(BI(2))], a new Pt species [(Cy(3)P)(I(2)B)Pt(mu-I)](2) was formed with concomitant buildup of the phosphine borane adduct [Cy(3)P-BI(3)]. The former is obviously obtained by abstraction of PCy(3) from trans-[(Cy(3)P)(2)Pt(I)(BI(2))] and the subsequent dimerization of two remaining fragments. Interestingly, the dimerization is reversible, and the dinuclear compound can be converted to trans [(Cy(3)P)(2)Pt(I)(BI(2))] upon the addition of PCy(3). PMID- 17854178 TI - Nickel-cysteine binding supported by phosphine chelates. AB - The effect of chelating phosphines was tested on the structure and pH-dependent stability of nickel-cysteine binding. (1,2-Bis(diphenylphosphino)ethane (dppe) and 1,1,1-tris[(diphenylphosphino)methyl]ethane (triphos) were used with three different cysteine derivatives (L-cysteine, Cys; L-cysteine ethyl ester, CysEt; cystamine, CysAm) to prepare complexes of the form (dppe)NiCysR(n+) and (triphos)NiCysR(n+) (n = 0 for Cys; n = 1 for CysEt and CysAm). Similar 31P {1H} NMR spectra for all (dppe)NiCysRn+ confirmed their square-planar P2NiSN coordination spheres. The structure of [(dppe)NiCysAm]PF6 was also confirmed by single-crystal X-ray diffraction methods. The (triphos)NiCysAm+ and (triphos)NiCysEt+ complexes were fluxional at room temperature by 31P NMR. Upon cooling to -80 degrees C, all gave spectra consistent with a P2NiSN coordination sphere with the third phosphorus uncoordinated. Temperature-dependent 31P NMR spectra showed that a trans P-Ni-S pi interaction controlled the scrambling of the coordinated triphos. In aqueous media, (dppe)NiCys was protonated at pH approximately 4-5, leading to possible formation of a nickel-cysteinethiol and eventual cysteine loss at pH < 3. The importance of N-terminus cysteine in such complexes was demonstrated by preparing (dppe)NiCys-bead and trigonal-bipyramidal Tp*NiCys-bead complexes, where Cys-bead represents cysteine anchored to polystyrene synthesis beads and Tp*- = hydrotris(3,5-dimethylpyrazolyl)borate. Importantly, results with these heterogeneous systems demonstrated the selectivity of these nickel centers for cysteine over methionine and serine and most specifically for N-terminus cysteine. The role of Ni-S pi bonding in nickel cysteine geometries will be discussed, including how these results suggest a mechanism for the movement of electron density from nickel onto the backbone of coordinated cysteine. PMID- 17854179 TI - Solvent-free aerobic oxidation of n-alkane by iron(III)-substituted polyoxotungstates immobilized on SBA-15. AB - The tetrairon(III)-substituted polytungstates [Fe(4)(H(2)O)(10)(beta XW(9)O(33))(2)](n-) (n = 6, X = As(III), Sb(III); n = 4, X = Se(IV), Te(IV)) were immobilized on (3-aminopropyl)triethoxysilane-modified SBA-15 and showed an excellent catalytic performance for solvent-free aerobic oxidation of long-chain n-alkanes using air as the oxidant under ambient conditions through a classical free-radical chain autoxidation mechanism. PMID- 17854180 TI - In situ generation of oxo-sulfidobis(dithiolene)tungsten(VI) complexes: active site models for the aldehyde ferredoxin oxidoreductase family of tungsten enzymes. AB - Oxo-sulfidobis(dithiolene)tungsten(VI) complexes were prepared in situ by the reaction of oxobis(dithiolene)tungsten(V) precursors with hydrosulfide (SH-). The complexes, characterized by UV-vis, electrospray ionization mass spectrometry, IR, and resonance Raman spectroscopies, model the proposed coordination environment and observed hydrolytic reactions of members of the aldehyde ferredoxin oxidoreductase family of tungsten enzymes. PMID- 17854181 TI - A triply interpenetrated microporous metal-organic framework for selective sorption of gas molecules. AB - A microporous metal-organic framework Zn(ADC)(4,4'-Bpe)(0.5).xG [1; ADC = 4,4' azobenzenedicarboxylate, 4,4'-Bpe = trans-bis(4-pyridyl)ethylene, G = guest molecules] with a triply interpenetrative primitive cubic net was synthesized and characterized. With pores of about 3.4 x 3.4 A, the activated 1a exhibits highly selective sorption behavior toward H(2)/N(2), H(2)/CO, and CO(2)/CH(4). PMID- 17854182 TI - Novel stereochemistry, reactivity, and stability of an arsenic heterocycle in a metal-promoted asymmetric cycloaddition reaction. AB - The organopalladium complex containing ortho-metalated (S)-[1 (dimethylamino)ethyl]phenylene as the chiral auxiliary has been used as the chiral template to promote the asymmetric cycloaddition reaction between diphenylvinylphosphine and 3,4-dimethyl-1-phenylarsole. A diphenylphosphino substituted asymmetrical heterobidentate arsanorbornene (As-P) ligand was obtained stereoselectively on the chiral palladium template in moderate yield. The chiral benzylamine auxiliary could be removed chemoselectively from the template by treatment with HCl to produce the neutral complex [(As-P)PdCl2]. In contrast to their reported P-P analogue, the arsenic donor in the dichloro complex could be eliminated stereospecifically under mild reaction conditions to generate the corresponding 1-(diphenylphosphino)-3,4-dimethyl-2,4-cyclohexadiene, which remained as a bidentate ligand at the PdCl2 unit via phosphorus and the eta2-C4-C5 double bond. The arsenic-elimination process was found to be influenced by the halo ligand in [(As-P)PdX2]. A similar process was observed with the analogous dibromo complex, but the corresponding diiodo species did not show similar reactivity. All of the novel As-Pd complexes have been characterized by X-ray crystallography. PMID- 17854184 TI - Tris(pyrrolyl-alpha-methyl)amines that sterically protect a trigonal metal site. AB - Three substituted tris(pyrrolyl-alpha-methyl)amines (H(3)[Aryl(3)TPA]) (Aryl = 2,4,6-C(6)H(2)Me(3), 2,4,6-C(6)H(2)(i-Pr)(3) (Trip), or 3,5-C(6)H(3)(CF(3))(2)) have been prepared. An X-ray study of [Trip(3)TPA]MoCl shows it to be a distorted trigonal bipyramidal species in which the 2,4,6-triisopropylphenyl substituents surround and protect the apical chloride. Attempts to prepare other Mo, Zr, and Hf complexes yielded species in which one pyrrole-containing arm remained free (Mo) or dimethylamine remained in the coordination sphere of [Aryl(3)TPA](3-) complexes (Zr, Hf). PMID- 17854183 TI - Four-stranded coordination helices containing silver-adenine (purine) metallaquartets. AB - This Communication describes structures of a family of silver-adenine (purine) metallaquartets that occur in a four-stranded coordination motif, bearing a close resemblance to nucleic acid quadruplexes. Using modified purine frameworks, it is further demonstrated that subtle variations in nucleobase heterocycle are tolerable and a metallaquartet is obtained irrespective of the substitution, thus suggesting a high-propensity silver-adenine interaction to achieve quartet structures. All of the solid-state structures studied were orthorhombic, belonging to the Fdd2 space group. PMID- 17854185 TI - Correlation of metal spin-state in alpha-diimine iron catalysts with polymerization mechanism. AB - The alpha-diimine iron complexes, (R',R'')[N,N]FeCl(2) ((R',R'')[N,N] = R'-N=CR' '-CR' '=N-R', where R' = tert-butyl (tBu), cyclohexyl (Cy) and R' ' = phenyl (Ph), para-fluorophenyl (F-Ph), para-bromophenyl (Br-Ph), para-methylphenyl (Me Ph), or para-methoxyphenyl (MeO-Ph)), are found to polymerize styrene through a catalytic chain transfer (CCT) mechanism. Magnetic moment measurements indicate that Fe(III) complexes containing these ligands possess intermediate (S = 3/2) spin-state iron centers. In contrast, Fe(III) complexes bearing proton (R' ' = H) and para-dimethylaminophenyl (R' ' = NMe(2)-Ph) substituents are high-spin and are efficient atom transfer radical polymerization (ATRP) catalysts. Hammett plots show a linear correlation of the substituent constant, sigma, with polymerization rate and polymer molecular weight, respectively. PMID- 17854186 TI - Ultramicroporous metal-organic framework based on 9,10-anthracenedicarboxylate for selective gas adsorption. AB - An ultramicroporous metal-organic framework based on 9,10-anthracenedicarboxylate (PCN-13) has been synthesized and structurally characterized. The desolvated PCN 13 demonstrates selective adsorption of oxygen and hydrogen over nitrogen and carbon monoxide. PMID- 17854187 TI - Polyoxometalates with internal cavities: redox activity, basicity, and cation encapsulation in [Xn+P5W30O110](15-n)- Preyssler complexes, with X = Na+, Ca2+, Y3+, La3+, Ce3+, and Th4+. AB - The Preyssler anion, of general formula [Xn+P5W30O110](15-n)-, is the smallest polyoxometalate (POM) with an internal cavity allowing cation exchange with the solution. The Preyssler anion features a rich chemistry evidenced by its ability to accept electrons at low potentials, to selectively capture various metal cations, and to undergo acid-base reactions. A deep understanding of these topics is herein provided by means of DFT calculations on the title series of compounds. We evaluate the energetics of the release/encapsulation process for several Xn+ cations and identify the effect of the encapsulated ion on the properties of the Preyssler anion. We revisit the relationship between the internal cation charge and the electrochemical behavior of the POM. A linear dependence between the first one-electron reduction energies and the encapsulated Xn+ charge is found, with a slope of 48 mV per unit charge. The protonation also shifts the reduction potential to more positive values, but the effect is much larger. In connection to this, the last proton's pKa = 2 for the Na+ derivative was estimated to be in reasonable agreement with experiment. The electronic structure of lanthanide derivatives is more complex than conventional POM structures. The reduction energy for the CeIV-Preyssler + 1e- --> CeIII-Preyssler process was computed to be more exothermic than that of very oxidant species such as S2Mo18O624-. PMID- 17854188 TI - A self-assembled nanofiber catalyst for ester hydrolysis. PMID- 17854189 TI - Carbon-hydrogen bond activation: two, three, or more mechanisms? PMID- 17854190 TI - Do ligand binding and solvent exclusion alter the electrostatic character within the oxyanion hole of an enzymatic active site? PMID- 17854191 TI - Cycloaddition reactions of thiazolium azomethine ylides: application to pyrrolo[2,1-b]thiazoles. AB - Thiazolium azomethine ylides, equipped with a C-2 methanethiol group, participate in an efficient [3 + 2] cycloaddition reaction with acetylene derivatives to yield unique pyrrolo[2,1-b]thiazoles. The elimination of the methanethiol leaving group from the cycloadduct has replaced the need for a separate oxidation step and suppresses ring-opening side reactions. Products were obtained in short synthetic sequences to demonstrate their use as a scaffold for compound libraries. PMID- 17854192 TI - Selective cross-couplings. Sequential Stille-Liebeskind/Srogl reactions of 3 chloro-4-arylthiocyclobutene-1,2-dione. AB - The synthesis and initial reactivity studies of 2 are described. It was found that it participates in Stille couplings exclusively at the C-Cl site with a number of organostannanes (58-71% yield) in the absence of Cu(I). Then, these new derivatives were functionalized at the C-S site with boronic acids by switching to the Liebeskind-Srogl reaction conditions (in the presence of a Cu(I) carboxylate) to yield the bifunctionalized cyclobutenediones (44-90% yield). PMID- 17854193 TI - Synthesis of nucleotide analogues by a promiscuous phosphoribosyltransferase. AB - An Escherichia coli strain overexpressing a mutant variant of a phosphoribosyl transferase was developed as a catalyst for the efficient preparation of a range of purine nucleotide analogues. This system offers an efficient and rapid method for nucleotide analogue synthesis with 100% beta-selectivity, providing analytically pure product in a single purification step. PMID- 17854194 TI - Oxa-bicyclocalixarenes: a new cage for anions via C-H...anion hydrogen bonds and anion...pi interactions. AB - Density functional theory calculations indicate that the cage molecule 4 can trap F- in the gas phase (-80.5 kcal/mol) as well as in CH2Cl2 (-14.7 kcal/mol) via strong C-H...F- hydrogen bonds and pi...F- interaction. PMID- 17854195 TI - Tandem molybdenum catalyzed hydrosilylations: an expedient synthesis of beta-aryl aldehydes. AB - The synthesis of beta-aryl aldehydes utilizing a tandem molybdenum catalyzed hydrosilylation is described. This new functional group interconversion provides an efficient method for the two-carbon homologation of aryl aldehydes. PMID- 17854196 TI - Finite-length models of carbon nanotubes based on Clar sextet theory. AB - Finite-length models of metallic and semiconducting carbon nanotubes (CNTs) based on Clar sextet theory of aromatic systems are proposed. For metallic CNTs, the electronic properties of finite-length models converge monotonically to the values expected for quasi-monodimensional metallic systems. For semiconducting CNTs, the use of finite-length models as proposed in this work leads to a fast convergence of the electronic properties to the values expected for the corresponding infinite-length nanotube. PMID- 17854197 TI - Improved biomimetic total synthesis of D,L-stephacidin A. AB - The direct conversion of beta-hydroxyproline derivatives into 5-hydroxypyrazin 2(1H)-ones under Mitsunobu conditions has been discovered to be a general biomimetic protocol generating IMDA intermediates and has been applied to the concise, biomimetic total syntheses of D,L-stephacidin A and D,L-brevianamide B. PMID- 17854198 TI - Computing reliable energetics for conjugate addition reactions. AB - The performance of various density functionals along with second-order perturbation treatments has been tested for a set of conjugate addition reactions relevant to stereoselective organocatalysis. It is shown that B3LYP predictions seriously underestimate the reaction energies, whereas two newly designed functionals (M05-2X and M06-2X) and the SCS-MP2 method provide very accurate data. These new methods represent promising alternative approaches in future mechanistic studies. PMID- 17854199 TI - Room temperature-stable electride as a synthetic organic reagent: application to pinacol coupling reaction in aqueous media. AB - Room temperature-stable inorganic electride [Ca(24)Al(28)O(68)](4+)4e(-) was employed for a pinacol coupling reaction in aqueous media. Ca-Al-O gel formed by the destruction of the crystal structure of an electride by water media played a key role in transferring the electron to electrophilic aldehydes. Aromatic aldehydes reacted smoothly with moderate to high yields. PMID- 17854200 TI - Gold-catalyzed multicomponent synthesis of aminoindolizines from aldehydes, amines, and alkynes under solvent-free conditions or in water. AB - A gold(III)-catalyzed multicomponent coupling/cycloisomerization reaction of heteroaryl aldehydes, amines, and alkynes under solvent-free conditions or in water has been developed. This methodology provides rapid access to substituted aminoindolizines with high atom economy and high catalytic efficiency. Especially, the coupling of enantiomerically enriched amino acid derivatives produces the corresponding N-indolizine-incorporated amino acid derivatives without loss of enantiomeric purity. PMID- 17854201 TI - Ir-catalyzed regio- and enantioselective decarboxylative allylic alkylations. AB - [Ir(COD)Cl]2/phosphoramidite ligand 1a was found to be an efficient catalytic system for the highly regio- and enantioselective decarboxylative alkylation of gamma-substituted allyl beta-ketocarboxylates, affording the branched products with up to >99/1 branched-linear ratio and 96% ee. PMID- 17854202 TI - Reduction of aldehydes and ketones by transfer hydrogenation with 1,4-butanediol. AB - 1,4-Butanediol has been used as the hydrogen donor in transfer hydrogenation reactions. The equilibrium is driven by the formation of gamma-butyrolactone, and the diol is therefore not required in excess. PMID- 17854203 TI - Selective isolation of N-blocked peptides by isocyanate-coupled resin. AB - We developed a method for selective isolation of N-blocked peptides from a complex mixture such as an enzymatic digest of a protein. The approach is based on a newly designed isocyanate-resin (resin-NCO), which specifically reacts with alpha-amino or imino groups. This method, then, permits the isolation of N blocked peptides, even those containing Lys, from a peptide mixture as intact forms by trapping N-free peptides via covalent bonding to the resin-NCO. The present study demonstrates the performance of this method for the selective isolation of N-blocked peptides by applying it to several peptide mixtures, including proteolytic digests. PMID- 17854204 TI - Reaction of Desulfovibrio vulgaris two-iron superoxide reductase with superoxide: insights from stopped-flow spectrophotometry. AB - Stopped-flow mixing of the Desulfovibrio vulgaris two-iron superoxide reductase (2Fe-SOR) containing the ferrous active site with superoxide generates a dead time intermediate whose absorption spectrum is identical to that of a putative ferric-hydroperoxo intermediate previously observed by pulse radiolysis. The dead time intermediate is shown to be a product of reaction with superoxide and to be generated at a much higher proportion of active sites than by pulse radiolysis. This intermediate decays smoothly to the resting ferric active site ( approximately 30 s-1 at 2 degrees C and pH 7) with no other detectable intermediates. Deuterium isotope effects demonstrate that solvent proton donation occurs in the rate-determining step of dead time intermediate decay and that neither of the conserved pocket residues, Glu47 or Lys48, functions as a rate determining proton donor between pH 6 and pH 8. Fluoride, formate, azide, and phosphate accelerate decay of the dead time intermediate and for azide or fluoride lead directly to ferric-azido or -fluoro complexes of the active site, which inhibit Glu47 ligation. A solvent deuterium isotope effect is observed for the azide-accelerated decay, and the decay rate constants are proportional to the concentrations and pKa values of HX (X- = F-, HCO2-, N3-). These data indicate that the protonated forms of the anions function analogously to solvent as general acids in the rate-determining step. The results support the notion that the ferrous SOR site reacts with superoxide by an inner sphere process, leading directly to the ferric-hydroperoxo intermediate, and demonstrate that the decay of this intermediate is subject to both specific- and general-acid catalysis. PMID- 17854205 TI - Selective modification of CaaX peptides with ortho-substituted anilinogeranyl lipids by protein farnesyl transferase: competitive substrates and potent inhibitors from a library of farnesyl diphosphate analogues. AB - Protein farnesyl transferase (FTase) catalyzes transfer of a 15-carbon farnesyl group from farnesyl diphosphate (FPP) to a conserved cysteine in the C-terminal Ca1a2X motif of a range of proteins ("C" refers to the cysteine, "a" to any aliphatic amino acid, and "X" to any amino acid), and the lipid chain interacts with, and forms part of, the Ca1a2X peptide binding site. Here, we employed a library of anilinogeranyl diphosphate (AGPP) derivatives to examine whether altering the interacting surface between the two substrates could be exploited to generate Ca1a2X peptide selective FPP analogues. Analysis of transfer kinetics to dansyl-GCVLS peptide revealed that AGPP analogues with substituents smaller than or equal in size to a thiomethyl group supported FTase function, while analogues with larger substituents did not. Analogues with small meta-substitutions on the aniline ring such as iodo and cyano increased reactivity with dansyl-GCVLS and provided analogues that were effective FPP competitors. Other analogues with ortho-substitutions on the aniline were potent dansyl-GCVLS modification FTase inhibitors (Ki in the 2.4-18 nM range). Both meta- and para-trifluoromethoxy-AGPP are transferred to dansyl-GCVLS while the ortho-substituted isomer was a potent farnesyl transferase inhibitor (FTI) with an inhibition constant Ki = 3.0 nM. In contrast, ortho-trifluoromethoxy-AGPP was efficiently transferred to dansyl GCVIM. Competition for dansyl-GCVLS and dansyl-GCVIM peptides by FPP and ortho trifluoromethoxy-AGPP gave both analogue and farnesyl modified dansyl-GCVIM but only farnesylated dansyl-GCVLS. We provide evidence that competitive modification of dansyl-GCVIM by ortho-trifluoromethoxy-AGPP stems from a prechemical step discrimination between the competing peptides by the FTase-analogue complex. These results show that subtle changes engineered into the isoprenoid structure can alter the reactivity and FPP competitiveness of the analogues, which may be important for the development of prenylated protein function inhibitors. PMID- 17854206 TI - Surface hydrophobicity modulates the operation of actomyosin-based dynamic nanodevices. AB - We studied the impact of surface hydrophobicity on the motility of actin filaments moving on heavy-meromyosin (HMM)-coated surfaces. Apart from nitrocellulose (NC), which is the current standard for motility assays, all materials tested are good candidates for microfabrication: hydrophilic and hydrophobic glass, poly(methyl methacrylate) (PMMA), poly(tert-butyl methacrylate) (PtBuMA), and a copolymer of O-acryloyl acetophenone oxime with a 4 acryloyloxybenzophenone (AAPO). The most hydrophilic (hydrophilic glass, contact angle 35 degrees) and the most hydrophobic (PtBuMA, contact angle 78 degrees) surfaces do not maintain the motility of actin filaments, presumably because of the low density of adsorbed HMM protein or its high levels of denaturation, respectively. The velocity of actin filaments presents higher values in the middle of this "surface hydrophobicity motility window" (NC, PMMA), and a bimodal distribution, which is more apparent at the edges of this motility window (hydrophobic glass and AAPO). A molecular surface analysis of HMM and its S1 units suggests that the two very different, temporally separated conformations of the HMM heads could exacerbate the surface-modulated protein behavior, which is common to all microdevices using surface-immobilized proteins. An explanation for the above behavior proposes that the motility of actin filaments on HMM functionalized surfaces is the result of the action of three populations of motors, each in a different surface-protein conformation, that is, HMM with both heads working (high velocities), working with one head (low velocities), and fully denatured HMM (no motility). It is also proposed that the molecularly dynamic nature of polymer surfaces amplifies the impact of surface hydrophobicity on protein behavior. The study demonstrates that PMMA is a good candidate for the fabrication of future actomyosin-driven dynamic nanodevices because it induces the smoothest motility of individual nano-objects with velocities comparable with those obtained on NC. PMID- 17854207 TI - Fine-tuning size of gold nanoparticles by cooling during reverse micelle synthesis. AB - By lowering the reaction temperature during metal ion reduction in a reverse micelle system, gold nanoparticle size can be subtly tuned from 6.6 to 2.2 nm in diameter. Under these reaction conditions, the water-to-surfactant ratio (W value) also plays an important role in controlling the particle size, enabling a wide range of products obtainable via a simple, quick, reproducible synthesis. Particle sizes were measured by HRTEM, and size trends were supported by UV-vis spectroscopy. PMID- 17854208 TI - Mixing aqueous ferric chloride and O-phenylenediamine solutions at room temperature: a fast, economical route to ultralong microfibrils of assemblied O phenylenediamine dimers. AB - The direct mix of aqueous ferric chloride and o-phenylenediamine (OPD) solutions at room temperature has been demonstrated for the first time to be an effective, economic, and fast method for preparing microfibrils on a large scale. The formation of such large microfibrils is attributed to the self-assembly of the OPD dimers generated by the oxidation of OPD monomers by ferric chloride. It is also interesting that the resulting microfibrils can be broken into shorter ones by a simple sonication process and the final length of the microfibrils obtained can be controlled by varying the sonication time. The influences of both the amount of ferric chloride and the oxidant type on the size and the morphology of the microstructures are also examined. PMID- 17854209 TI - Assembly of highly ordered nanoparticle monolayers at a water/hexane interface. AB - This paper reports a methodology for preparing ordering hydrophilic metal nanoparticles into close-packed 2-dimensional arrays at a hexane-water interface with alkanethiol in the hexane layer. The destabilization of metal nanoparticles by the addition of alcohol caused the nanoparticles to adsorb to an interface where the surface of entrapped Au nanoparticle was in situ coated with the long chain alkanethiols present in a hexane layer. The adsorption of alkanethiol to the nanoparticle surface caused the conversion of the electrostatic repulsive force to a van der Waals interaction, which is a key feature in forming highly ordered close-packed nanoparticle arrays. PMID- 17854210 TI - Electrochemical deposition and characterization of mixed-valent rhenium oxide films prepared from a perrhenate solution. AB - Cathodic electrodeposition of mixed-valent rhenium oxides at indium tin oxide, gold, rhenium, and glassy carbon electrodes from acidic perrhenate solutions (pH = 1.5 +/- 0.1) prepared from hydrogen peroxide and zerovalent rhenium metal is described. Cyclic voltammetry, variable angle spectroscopic ellipsometry (VASE), X-ray photoelectron spectroscopy (XPS), UV-vis spectroelectrochemistry, and electrochemical quartz crystal microbalance (EQCM) data indicate that the chemical nature of the electrodeposited rhenium species depends mainly upon the potential and supporting electrolyte. The presence of SO4(2-) as a supporting electrolyte inhibits the adsorption of perrhenate, ReO4-, at non-hydrogen adsorbing electrode materials. However, in acidic perrhenate solutions containing only protons and ReO4- anions, strong adsorption of ReO4- at potentials preceding hydrogen evolution occurs. This leads to the formation of an unstable ReIII2O3 intermediate which catalytically disproportionates to form mixed-valent rhenium films consisting of 72% ReIVO2 and 28% Re0. During the hydrogen evolution reaction (HER), hydrogen polarization causes the principle deposit to be more reduced, consisting of roughly 64% ReIVO2 and 36% Re0. Conclusively, metallic rhenium can be deposited at potentials preceding the HER at non-hydrogen adsorbing electrode materials, especially in the absence of SO4(2-) anions. PMID- 17854211 TI - Poly(N-vinylcaprolactam-co-glycidyl methacrylate) aqueous microgels labeled with fluorescent LaF3:Eu nanoparticles. AB - We describe the synthesis and properties of functional microgel particles based on poly(N-vinylcaprolactam-co-glycidyl methacrylate) (PVCL/PGMA) copolymer. A series of colloidally stable microgel particles with a range of glycidyl methacrylate content were prepared by surfactant-free heterophase polymerization in water. The microgel particles obtained had hydrodynamic radii between 250 and 350 nm and were fairly monodisperse in size; however, a broadening of the particle size distribution was observed for samples with a low GMA content. The PVCL/PGMA microgel particles exhibit thermally responsive reversible changes in diameter in water, and the swelling degree increased with the PVCL fraction in the copolymer structure. These microgels were then modified with photoluminescent europium-doped lanthanum fluoride nanoparticles (LaF3:Eu-AEP) through reaction of the 2-aminoethyl phosphate surface ligands with epoxy groups present in the microgel. These hybrid microgels were colloidally stable and thermally responsive in aqueous solution. PMID- 17854212 TI - Bi-phobic cellulose fibers derivatives via surface trifluoropropanoylation. AB - The surface modification of cellulose fibers with 3,3,3-trifluoropropanoyl chloride (TFP) was studied in a toluene suspension. The characterization of the modified fibers was performed by elemental analysis, Fourier transform infrared (FTIR), 13C-solid-state NMR, X-ray diffraction, thermogravimetry, and surface analysis (XPS, ToF-SIMS, and contact angles measurements). The degree of substitution (DS) of the ensuing trifluoropropanoylated fibers ranged from less than 0.006 to 0.30, and in all instances the fibers' surface acquired a high hydrophobicity and lipophobicity resulting from a drastic reduction in its energy. The hydrolytic stability of these cellulose derivatives was also evaluated and shown to be permanent in time in the presence of neutral water, still appreciable in basic aqueous solution at pH 9, but, as expected quite poor at pH 12. PMID- 17854213 TI - Approximate analytical expressions for the electrical potential in a cavity containing salt-free medium. AB - The electrical potential in a closed surface such as a cavity containing counterions only is derived for the cases of constant surface potential and constant surface charge density. The results obtained have applications in, for example, microemulsion-related systems in which ionic surfactants are introduced to maintain the stability of a dispersion and electroosmotic flow-related analysis. An analytical expression for the electrical potential is derived for a planar slit, and the methodology used is modified to derive approximate analytical expressions for spherical and cylindrical cavities. The higher the surface potential, the better the performance of these expressions. For the case where the surface potential is above ca. 50 mV, the performance of the approximate analytical expressions can further be improved by multiplying a correction function. PMID- 17854214 TI - AFM studies of inhibition effect in binding of antimicrobial peptide and immune proteins. AB - By using atomic force microscopy (AFM), we clearly show that the antimicrobial peptide affects the molecular interaction between lipopolysaccharide (LPS) and immune proteins (lipopolysaccharide binding protein [LBP] and CD14). To reconstruct an in vivo interaction, LBP and LPS (the Ra, Rc, and Re forms from Salmonella minnesota, with varying lengths of the saccharide region) were immobilized onto the AFM tip using a chemical spacer linker. We examined the interaction between the proteins on the tip and model lipid bilayer biomembranes including CD14, in both the presence and absence of the antimicrobial peptide, polymyxin B (PMB). When LPS was present, the binding force between the LBP-LPS complex and CD14 increased dramatically, compared to that seen between LBP and CD14 alone. Longer LPS saccharide regions resulted in higher binding forces. The data suggest that LPS may have an important influence on the binding of LBP to CD14 and that the saccharide region of LPS is influential in this regard. It was also found that the antimicrobial peptide PMB, at or above a particular concentration, specifically inhibited the binding between LBP-LPS and CD14. PMID- 17854216 TI - A simple intact protein analysis by MALDI-MS for characterization of ribosomal proteins of two genome-sequenced lactic acid bacteria and verification of their amino acid sequences. AB - Rapid identification of bacteria by a bioinformatics-based approach, which processes the mass spectra observed by matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS), relies on the calculated masses of ribosomal subunit proteins as biomarkers predicted from amino acid sequences found in protein sequence databases. To verify the actual state of the registered sequence information, a simple intact protein analysis by MALDI-MS using cell lysates as samples was applied to the characterization of ribosomal proteins from genome-sequenced Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus strains. This method avoided the risk of loss of some subunit proteins and the formation of disulfide bonds during the purification of ribosomal proteins. By comparing this with the MALDI mass spectra of different strains and carrying out manual inspection of sequence information, a total of five errors in N-terminal amino acid sequences were identified. After sequence correction, approximately 40 out of 53 subunit proteins could be assigned, considering N-terminal methionine loss only as a post-translational modification. These show promise for use as practical biomarkers for the rapid identification of S. thermophilus and L. bulgaricus. After verification of these amino acid sequences, mass differences relative to those of genome-sequenced strains have the potential for distinguishing bacteria at the strain level. PMID- 17854217 TI - Shotgun cross-linking analysis for studying quaternary and tertiary protein structures. AB - We developed a new approach that employs a novel computer algorithm for the sensitive and high-throughput analysis of tertiary and quaternary interaction sites from chemically cross-linked proteins or multi-protein complexes. First, we directly analyze the digests of the chemically cross-linked proteins using only high-accuracy LC-MS/MS data. We analyze these data using a computer algorithm, we term X!Link, to find cross-links between two peptides. Our algorithm is rapid, taking only a few seconds to analyze approximately 5000 MS/MS spectra. We applied this algorithm to analyze cross-linked sites generated chemically using the amino specific reagent, BS3, in both cytochrome c and the mitochondrial division dynamin mutant, Dnm1G385D, which exists as a stable homodimer. From cytochrome c, a well-established test protein, we identified a total of 31 cross-links, 21 interpeptide and 10 intrapeptide cross-links, in 257 MS/MS spectra from a single LC-MS/MS data set. The high sensitivity of this technique is indicated by the fact that all 19 lysines in cytochrome c were detected as a cross-link product and 33% of all the Lys pairs within 20 A were also observed as a cross-link. Analysis of the cross-linked dimeric form of Dnm1G385D identified a total of 46 cross-links, 38 interpeptide and 8 intrapeptide cross-links, in 98 MS/MS spectra in a single LC-MS/MS data set. These results represent the most abundant cross links identified in a single protein or protein dimer to date. Statistical analysis suggests a 1% false discovery rate after optimization of filtering parameters. Further analysis of the cross-links identified using our approach indicates that careful manual inspection is important for the correct assignment of cross-linking sites when multiple cross-linkable sites or several similar sequences exist. In summary, we have developed a sensitive MS-based approach to identify peptide-peptide cross-links that does not require isotopic labeling or comparison with non-cross-linked controls, making it faster and simpler than current methodologies. PMID- 17854218 TI - Proteomics-based strategy to delineate the molecular mechanisms of the metastasis suppressor gene BRMS1. AB - The breast cancer metastasis suppressor 1 (BRMS1) gene has been shown to suppress metastasis without affecting the growth of the primary tumor in mouse models. It has also been shown to suppress the metastasis of tumors derived from breast, melanoma, and, more recently, ovarian carcinoma (see ref 1). However, how BRMS1 exerts its metastasis suppressor function remains unknown. To shed light into its metastatic mechanism of action, the sensitive 2D-DIGE analysis coupled with MS has been used to identify proteins differentially expressed by either overexpressing (Mel-BRMS1) or silencing BRMS1 (sh635) in a melanoma cell line. After comparison of the protein profiles from WT, Mel-BRMS1, and sh635 cells, 79 spots were found to be differentially expressed. Mass spectrometry analysis allowed the unambiguous identification of 55 polypeptides, corresponding to 43 different proteins. Interestingly, more than 75% of the identified proteins were down-regulated in Mel-BRMS1 cells compared to WT. In contrast, all the identified proteins in sh635 cells extracts were up-regulated compared to WT. Most of the deregulated proteins are involved in cell growth/maintenance and signal transduction among other cell processes. Six differentially expressed proteins (Hsp27, Alpha1 protease inhibitor, Cofilin1, Cathepsin D, Bone morphogenetic protein receptor2, and Annexin2) were confirmed by immunoblot and functional assays. Excellent correlation was found between DIGE analysis and immunoblot results, indicating the reliability of the analysis. Available evidence on the reported functions of the identified proteins supports the emerging role of BRMS1 as negative regulator of the metastasis development. This work opens an avenue for the molecular mechanisms' characterization of metastasis suppressor genes with the aim to understand their roles. PMID- 17854219 TI - Effect of the solvatation shell exchange on the formation of malvidin-3-O glucoside-ellagic acid complexes. AB - The interaction of malvidin-3-O-glucoside with ellagic acid was studied in aqueous solutions in dependence of the ethanol content of the samples. The results show significant changes of the thermodynamic parameters when the ethanol content exceeds 8%vol. The quantum chemical calculations and the solvent relaxation measurements validate that the solvatation shell of the malvidin ellagic acid complexes changes from water to ethanol around this critical alcoholic concentration. The change of the solvate shell is accompanied by increasing copigmentation; i.e., higher "multi-sandwich" complexes are formed. According to the considerable role of this interaction (namely copigmentation) in the formation of color in red wines, our results have several consequences for the winemaking process with regard to the stabilization of wine color. PMID- 17854220 TI - Nanoscale energy deposition by X-ray absorbing nanostructures. AB - Here we wish to demonstrate a unique property of nanomaterials: energy deposition with nanometer precision from low-energy electrons released from these nanostructures interacting with hard X-ray radiation in aqueous solution. Three effects combine to cause this phenomenon: (1) localized absorption of X-rays by nanostructures, (2) effective release of low-energy electrons from small nanostructures, and (3) efficient deposition of energy in water in the form of radicals and electrons. This combination creates localized X-ray absorption and localized energy deposition of nanometer precision. We confirmed the theoretically predicted nanoscale energy deposition distribution by measuring hydroxyl radical-induced DNA strand breaks, and observed enhanced damage to a 5600-bp DNA molecule from approximately 10 chemically conjugated small gold nanoparticles under X-ray radiation. These results provide a general guidance to applications of this new concept in many fields including radiation chemistry, radiology, radiation oncology, biochemistry, biology, and nanotechnology. PMID- 17854222 TI - Stability of tubular structures based on beta-helical proteins: self-assembled versus polymerized nanoconstructs and wild-type versus mutated sequences. AB - In this work we used atomistic molecular dynamics simulations to examine different aspects of tubular nanostructures constructed using protein building blocks with a beta-helical conformation. Initially, we considered two different natural protein building blocks, which were extracted from the protein data base, to compare the relative stabilities of the nanotubes obtained made of self assembled and covalently linked repeats. Results show nanotubes constructed by linking building blocks through covalent bonds are very stable suggesting that the basic principles of polymer physics are valid when the repeating units are made of large fragments of proteins. In contrast, the stability of self-assembled nanostructures strongly depends on the attractive nonbonding interactions associated to building blocks aligned in a complementary manner. On the other hand, we investigated the ability of a conformationally constrained synthetic amino acid to enhance the stability of both self-assembled and polymerized nanotubes when it is used to substitute natural residues. Specifically, we considered 1-aminocyclopentane-1-caboxylic acid, which involves strong stereochemical constraints produced by the cyclopentane side chain. We found that the incorporation of this amino acid within the more flexible regions of the beta helical building blocks is an excellent strategy to enhance the stability of the nanotubes. Thus, when a single mutation is performed in the loop region of the beta-helix, the bend architecture of the whole loop is stabilized since the conformational mobility is reduced not only at the mutated position but also at the adjacent positions. PMID- 17854223 TI - The specific recognition of a cell binding sequence derived from type I collagen by Hep3B and L929 cells. AB - In this study, the affinity of two different cell types toward a specific cell binding sequence (Gly-Phe-Hyp-Gly-Glu-Arg or GFOGER) derived from type I collagen using peptide template (PT)-assembled collagen peptides of different triple helicity as a model for natural collagen is examined. A series of biophysical studies, including melting curve analysis and circular dichroism spectroscopy, demonstrated the presence of stable triple-helical conformation in the PT assembled (GPO)3-GFOGER-(GPO)3, (GPO)-GFOGER-(GPO), and (Pro-Hyp-Gly)5 solution. Conversely, non-templated peptides, except (GPO)3-GFOGER-(GPO)3, showed no evidence of assembly into triple-helical structure. Biological assays, including cell adhesion, competitive inhibition, and immunofluorescence staining, revealed a correlation of triple-helical conformation with the cellular recognition of GFOGER in an integrin-specific manner. The triple helix was shown to be important, but not crucial for cell adhesion to native collagen. Hep3B and L929 cells displayed significant differences in the recognition of GFOGER, mainly because of the differences in their expression of specific integrin receptors for collagen. For example, PT-assembled (GPO)3-GFOGER-(GPO)3 was shown to perform comparably to collagen for L929, but not Hep3B, cell adhesion. The result showed that a specific cell binding motif may not fully mimic the extracellular matrix (ECM) microenvironment, suggesting the need to use a combination of two or more cell binding sequences for targeting a wide range of integrin receptors expressed by a specific cell type to better mimic the ECM. PMID- 17854224 TI - Triplet energy dissipation in methylenecyclopropane rearrangement. AB - Certain 1,1-dimethyl-2-aryl-3-methylenecyclopropanes containing carbonyl substituents undergo rearrangement when irradiated with 350 nm light. These rearrangements occur via the (n,pi*) triplet state, which fragments the strained cyclopropane bond. Intersystem crossing followed by ring closure gives the observed products. No photoreduction is seen in i-PrOH. Potential Norrish type II processes are also bypassed. It is suggested that the cyclopropane bond fragmentation dissipates the triplet energy and that the new intermediates are not energetic enough to abstract hydrogen atoms in an intramolecular fashion or from solvent. Nitro substituted systems undergo analogous photoinitiated rearrangements. Benzophenone sensitization of naphthyl, biphenyl, styrene, and phenylacetylene analogues also leads to rearrangement, presumably via the sensitized generation of triplet states. When triplet states cannot be accessed by direct irradiation or by sensitized processes, methylenecyclopropane rearrangements do not occur. An exception is the ferrocenyl analogue, which does not photorearrange, presumably due to the very short lifetime of the triplet intermediate. PMID- 17854226 TI - Optical bonding using silica nanoparticle sol-gel chemistry. AB - A simple method is described to bond optical components using silica nanoparticle sol-gel chemistry. The silica nanoparticles polymerize into highly branched networks that link the surfaces together. The nanoparticle mediated bonding has several advantages to currently used optical joining technologies. The bonding is a room-temperature process and does not require any clean room facilities. The bonded interface has a high mechanical strength and low scattering. The bonding is resistant to organic solvents on silylation with hydrophobic surface groups. This method achieves 100% successful bonding rates between soda-lime glass slides. The bond-setting time can be tailored to allow time for precision optical alignment. PMID- 17854227 TI - Quantum dot-aptamer conjugates for synchronous cancer imaging, therapy, and sensing of drug delivery based on bi-fluorescence resonance energy transfer. AB - We report a novel quantum dot (QD)-aptamer(Apt)-doxorubicin (Dox) conjugate [QD Apt(Dox)] as a targeted cancer imaging, therapy, and sensing system. By functionalizing the surface of fluorescent QD with the A10 RNA aptamer, which recognizes the extracellular domain of the prostate specific membrane antigen (PSMA), we developed a targeted QD imaging system (QD-Apt) that is capable of differential uptake and imaging of prostate cancer cells that express the PSMA protein. The intercalation of Dox, a widely used antineoplastic anthracycline drug with fluorescent properties, in the double-stranded stem of the A10 aptamer results in a targeted QD-Apt(Dox) conjugate with reversible self-quenching properties based on a Bi-FRET mechanism. A donor-acceptor model fluorescence resonance energy transfer (FRET) between QD and Dox and a donor-quencher model FRET between Dox and aptamer result when Dox intercalated within the A10 aptamer. This simple multifunctional nanoparticle system can deliver Dox to the targeted prostate cancer cells and sense the delivery of Dox by activating the fluorescence of QD, which concurrently images the cancer cells. We demonstrate the specificity and sensitivity of this nanoparticle conjugate as a cancer imaging, therapy and sensing system in vitro. PMID- 17854228 TI - Layer-in-layer hierarchical nanostructures fabricated by combining holographic polymerization and block copolymer self-assembly. AB - We report the combination of top-down and bottom-up nanomanufacturing techniques to fabricate active, hierarchically structured volume reflection gratings. Holographic polymerization (H-P) formed lamellar structures of approximately 200 nm in thickness, confining a block copolymer (BCP) to approximately 100 nm domains. Subsequently, the BCP self-assembles into nanolayers with a period of approximately 21 nm. We envisage that this approach opens a gateway to fabricating hierarchical nanostructures at different length scales. PMID- 17854229 TI - Influence of the sensitizer adsorption mode on the open-circuit potential of dye sensitized solar cells. AB - We report a combined experimental and theoretical study on the origin of the different open circuit potentials observed in dye-sensitized solar cells using Ru(II)-polypyridyl homoleptic and heteroleptic sensitizers. We have measured the photovoltaic data of different sensitizers and used DFT calculations to analyze the electronic structure of dye-sensitized TiO(2) nanoparticles. Heteroleptic sensitizers adsorb onto TiO(2) via a single bipyridine, leading to a TiO(2) conduction band downshift and overall reduction of the cell open circuit potential. PMID- 17854230 TI - Strength weakening by nanocrystals in ceramic materials. AB - A key question in nanomechanics concerns the grain size effects on materials' strength. Correct solution to this question is critical to design and tailor the properties of materials for particular applications. The full map of grain sizes hardness/yield stress relationship in metals has been built. However, for ceramic materials, the similar studies and understandings are really lacking. Here we employed a novel technique to comparatively study the mechanical features of titanium dioxide (TiO(2)) with different crystallite sizes. On the basis of peak profile analysis of the X-ray diffraction data, we determined yield strength for nanocrystalline and bulk TiO(2). Our results reveal a remarkable reduction in yield strength as the grain size decreases from 30-40 microm to approximately 10 nm, providing the only evidence of a strength weakening by nanocrystals relative to their bulk counterparts. This finding infers an inverse Hall-Petch effect, the first of its kind for ceramic materials, and a dramatic strength weakening after the breakdown of classic Hall-Petch relation below a characteristic grain size. PMID- 17854231 TI - A general approach for transferring hydrophobic nanocrystals into water. AB - Hydrophobic inorganic nanocrystals have been transferred from organic solvent to aqueous solution through a robust and general ligand exchange procedure. Polyelectrolytes such as poly(acrylic acid) and poly(allylamine) are used to replace the original hydrophobic ligands on the surface of nanocrystals at an elevated temperature in a glycol solvent and eventually render the nanocrystals highly water soluble. The physical properties of the nanocrystals, such as superparamagnetism, photocatalytic activity, and photoluminescence, are maintained or improved after ligand exchange. PMID- 17854232 TI - Clinical translation of genotyping and haplotyping data: implementation of in vivo pharmacology experience leading drug prescription to pharmacotyping. AB - The completion of the Human Genome Project has raised expectations for the translation of genomic knowledge into clinical forms that would lead to improved diagnosis of diseases and identification of new drug targets. Such an opportunity is quite challenging within science and society, although there is still uncertainty regarding its outcomes in new drug development and healthcare. Undoubtedly, however, the recent approval by the US FDA of the first two pharmacogenomic tests for genotyping drug-metabolising enzymes is expected to empower and eventually lead to general applicability of various genetic diagnostic tools to improve pharmacotherapy outcomes in the post-genomic era. To this end, the application of genomic knowledge and technologies in everyday clinical practice leads personalised medicine concepts towards the achievement of individualised drug selection and dosage profiling (i.e. pharmacotyping) for ensuring maximum drug effectiveness and safety. Within this framework, pharmacogenomic information can implement the existing clinical pharmacology experience in clinical diagnosis and drug delivery. The latter can be further advanced through the development of workflow information-based operating systems in healthcare to support the utilisation, assessment and outcome of engaged clinical and genomic information. Such a direction may help to suitably revise and adjust clinical regulatory guidelines as well as clinical pharmacology guidelines. This will further facilitate better designing of clinical trials for new drug development as well as pharmacovigilance registries and evaluation of these data. To critically describe the existing environment, this article comprehensively discusses scientific efforts aimed at making clinical translation of genotyping and haplotyping data more efficient and productive in forms that are readily applicable in everyday healthcare. In addition, specific and systematic pharmacogenomic and clinical attempts related to the development of new molecularly targeted drugs, as well as improvement of the efficacy and safety of commonly prescribed drugs, are presented. To this end, the clinical pharmacogenomic experience gained thus far in the use of tyrosine kinase inhibitors in oncology, as well as the process of empowerment through the use of genomic knowledge of the cardiac safety of drugs modulating the function of the human ether-a-go-go-related gene (HERG) potassium channel, represent examples of how the implementation of clinical experience with genomic information guides the development of new drugs and the improvement of pharmacotherapy outcomes. PMID- 17854234 TI - Transdermal administration of radiolabelled [14C]rotigotine by a patch formulation: a mass balance trial. AB - BACKGROUND AND OBJECTIVE: The dopamine agonist rotigotine has been formulated in a silicone-based transdermal system for once-daily administration. The objective of the present study was to characterise the mass balance of rotigotine in humans after administration of a single transdermal patch containing radiolabelled [(14)C]rotigotine and to quantify the pharmacokinetic profiles of total radioactivity and the corresponding rotigotine plasma concentrations. METHODS: In a phase I trial, six healthy male Caucasian subjects were administered a single 10 cm(2) patch containing 4.485mg of unlabelled and 0.015mg of [(14)C]-labelled rotigotine (total radioactivity 0.09 MBq per patch) with a patch-on period of 24 hours. Radioactivity was determined by liquid scintillation counting in unused patches, used patches, skin wash samples after 24 hours, plasma, urine and faeces samples up to 96 hours and skin stripping samples at 96 hours post-application. Unconjugated rotigotine in plasma samples was determined by liquid chromatography with tandem mass spectrometry. Plasma samples were taken predose and 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours after patch application. RESULTS: The rotigotine transdermal patch was well tolerated, and all subjects completed the trial. A total of 94.6% of the administered dose was recovered within 96 hours after patch application inclusive of the residual amounts in the patch. Within 24 hours, 51% of the total radioactivity was delivered to the human body system and 46.1% was systemically absorbed. Total radioactivity recovered in urine and faeces was 30.4% and 10.2%, respectively, of the radioactivity applied (corresponding to 65.8% and 21.8% of the dose absorbed, respectively). CONCLUSIONS: The mass balance of rotigotine within 96 hours after transdermal delivery of rotigotine via a 10 cm(2) [(14)C]rotigotine patch with a total drug content of 4.5mg (corresponding to the nominal dose of 2mg/24 hours for the marketed rotigotine transdermal system) has been 95% explained. The systemic absorption was 46.1% of the administered dose, the majority of which was cleared from the body via urine and faeces within 96 hours after patch application. PMID- 17854235 TI - Correlation of the pharmacokinetic parameters of amikacin and ceftazidime. AB - BACKGROUND AND OBJECTIVES: Ceftazidime and amikacin are often prescribed concomitantly to treat infections caused by Gram-negative bacteria. Their physicochemical properties are quite similar. Both drugs are highly soluble in water, have low plasma protein binding and are >95% excreted unchanged by the kidney via glomerular filtration. Their pharmacokinetic parameters are therefore expected to correlate. This study was performed to explore the correlation between the pharmacokinetic parameters of these two drugs. PATIENTS AND METHODS: Patients at Phramongkutklao Hospital, Bangkok, Thailand, who met the inclusion criteria participated in the study. They all received ceftazidime and amikacin concomitantly to treat their infections. After steady-state conditions had been reached, two blood samples were collected during the elimination phase of both drugs. Plasma drug concentrations were analysed and the pharmacokinetic parameters of each drug were calculated. The pharmacokinetic parameters that were examined included total drug clearance (CL), the elimination rate constant (k(e)), the elimination half life (t(1/2)) and the volume of distribution (V(d)). The correlations of the pharmacokinetic parameters of amikacin and ceftazidime were determined using regression analysis. RESULTS: Regression analysis showed that the pharmacokinetic parameters of ceftazidime and amikacin were highly correlated. The correlation coefficients (r) of CL, k(e), t(1/2) and V(d) of the two drugs were 0.966, 0.943, 0.888 and 0.671, respectively. The correlation between amikacin clearance and ceftazidime clearance was higher than the correlation between either amikacin or ceftazidime clearance and creatinine clearance, for which the r values were 0.647 and 0.661, respectively. CONCLUSIONS: The pharmacokinetic parameters of ceftazidime and amikacin were highly correlated. Knowledge of the pharmacokinetic parameters of one of these drugs can be used to predict the pharmacokinetic parameters of the other drug. PMID- 17854233 TI - Cholestasis and endogenous opioids: liver disease and exogenous opioid pharmacokinetics. AB - A class of endogenous opioids is upregulated in liver disease particular to cholestasis, which contributes to symptoms in liver disease such as pruritus, hypotension and encephalopathy. Symptoms associated with cholestasis are reversed or at least ameliorated by mu opioid receptor antagonists. Palliation of symptoms related to cholestatic liver disease also involves bile acid binding agents. Opioid receptor antagonists, unlike bile acid binding agents, have been reported to relieve multiple symptoms, except for pruritus, and improve liver function as demonstrated in experimental cholestasis. Exogenous opioid pharmacology is altered by liver disease. Dose reduction or prolongation of dose intervals is necessary depending on the severity of liver disease. PMID- 17854236 TI - Population pharmacokinetic meta-analysis of trabectedin (ET-743, Yondelis) in cancer patients. AB - OBJECTIVE: To characterise the population pharmacokinetics of trabectedin (ET 743, Yondelis(R)) in cancer patients. METHODS: A total of 603 patients (945 cycles) receiving intravenous trabectedin as monotherapy at doses ranging from 0.024 to 1.8 mg/m(2) and given as a 1-, 3- or 24-hour infusion every 21 days; a 1 or 3-hour infusion on days 1, 8 and 15 of a 28-day cycle; or a 1-hour infusion daily for 5 consecutive days every 21 days were included in the analysis. An open four-compartment pharmacokinetic model with linear elimination, linear and nonlinear distribution to the deep and shallow peripheral compartments, respectively, and a catenary compartment off the shallow compartment was developed to best describe the index dataset using NONMEM V software. The effect of selected patient covariates on trabectedin pharmacokinetics was investigated. Model evaluation was performed using goodness-of-fit plots and relative error measurements for the test dataset. Simulations were undertaken to evaluate covariate effects on trabectedin pharmacokinetics. RESULTS: The mean (SD) trabectedin elimination half-life was approximately 180 (61.4) hours. Plasma accumulation was limited when trabectedin was given every 3 weeks. Systemic clearance (31.5 L/h, coefficient of variation 51%) was 19.2% higher in patients receiving concomitant dexamethasone. The typical values of the volume of distribution at steady state for male and female patients were 6070L and 5240L, respectively. Within the range studied, age, body size variables, AST, ALT, alkaline phosphatase, lactate dehydrogenase, total bilirubin, creatinine clearance, albumin, total protein, Eastern Cooperative Oncology Group performance status and presence of liver metastases were not statistically related to trabectedin pharmacokinetic parameters. The pharmacokinetic parameters of trabectedin were consistent across the infusion durations and dose regimens evaluated. CONCLUSIONS: The integration of trabectedin pharmacokinetic data demonstrated linear elimination, dose-proportionality up to 1.8 mg/m(2) and time independent pharmacokinetics. The pharmacokinetic impact of dexamethasone and sex covariates is probably limited given the moderate to large interindividual pharmacokinetic variability of trabectedin. The antiemetic and hepatoprotective effects are still a valid rationale to recommend dexamethasone as a supportive treatment for trabectedin. PMID- 17854237 TI - Lack of bioequivalence between different formulations of isosorbide dinitrate and hydralazine and the fixed-dose combination of isosorbide dinitrate/hydralazine: the V-HeFT paradox. AB - OBJECTIVE: To investigate whether the apparent discrepancy between the efficacy of the combination of isosorbide dinitrate (ISDN) and hydralazine demonstrated in the first V-HeFT trial (V-HeFT I) and that in V-HeFT II could be explained by pharmacokinetic differences in the study drug formulations, and to compare the pharmacokinetic profile of the fixed-dose combination of ISDN/hydralazine (FDC ISDN/HYD; BiDil) formulation used in A-HeFT with that of the V-HeFT study drug formulations. STUDY PARTICIPANTS AND METHODS: A bioequivalence study was performed (n = 18-19 per group) comparing the ISDN and hydralazine formulations used in V-HeFT I, V-HeFT II and A-HeFT in healthy volunteer men and women aged 18 40 years. In phase A of the study, subjects received a reference solution of hydralazine hydrochloride/ISDN (37.5mg/10mg) orally. Slow acetylators were identified and randomised into three groups in phase B to receive a single oral dose of identical amounts of hydralazine hydrochloride/ISDN (37.5mg/10mg) from either (i) a hydralazine capsule plus an ISDN tablet (the V-HeFT I formulation); (ii) a hydralazine tablet plus an ISDN tablet (the V-HeFT II formulation); or (iii) FDC ISDN/HYD (the A-HeFT formulation). Blood/plasma concentrations of hydralazine and ISDN were determined from the blood samples taken between 0 and 36 hours. RESULTS: In phase B, the maximum observed concentrations (C(max)) were 65.9 +/- 53.9, 28.2 +/- 15.8 and 51.5 +/- 54.3 ng/mL of unchanged hydralazine, and 23.1 +/- 12.3, 21.7 +/- 13.4 and 26.7 +/- 18.7 ng/mL of ISDN for the V-HeFT I, V-HeFT II and A-HeFT formulations, respectively. The area under the blood/plasma concentration-time curve (AUC) values were 32.6 +/- 13.4, 23.3 +/- 15.1 and 32.6 +/- 18.5 ng x h/mL of hydralazine, and 24.4 +/- 9.0, 24.8 +/- 8.0 and 23.5 +/- 6.3 ng x h/mL of ISDN for the V-HeFT I, V-HeFT II and A-HeFT formulations, respectively. For comparison of bioequivalence, the C(max) and AUC were normalised to 65kg bodyweight, and point estimates and 90% confidence intervals of the C(max) ratios, AUC ratios and ratios of the AUC in phase B normalised for clearance by the AUC in phase A (AUCR) were calculated. The three formulations were not bioequivalent based on the C(max) and AUC comparisons. CONCLUSIONS: The blood concentrations of hydralazine obtained with the tablet formulation tested in V-HeFT II were markedly lower than those obtained with the capsule formulation tested in V-HeFT I or the FDC ISDN/HYD single tablet used in A-HeFT. The apparently modest effect on survival observed in V-HeFT II could be explained in part by the poor hydralazine bioavailability of the tablet preparation used in this trial. ISDN exposures were similar in the two trials. The ISDN-hydralazine formulation used in V-HeFT II was not bioequivalent to the formulation used in V-HeFT I or to the FDC ISDN/HYD that had demonstrated a significant survival benefit in A-HeFT. PMID- 17854238 TI - Management of adnexal mass. AB - OBJECTIVES: To assess diagnostic strategies for distinguishing benign from malignant adnexal masses. DATA SOURCES: MEDLINE(R) and reference lists of recent reviews; discharge data from the Nationwide Inpatient Sample. REVIEW METHODS: The major diagnostic methods evaluated were bimanual pelvic examination, ultrasound (morphology and Doppler velocimetry), MRI, CT, FDG-PET, CA-125, and scoring systems that incorporated multiple clinical, laboratory, and radiologic findings. Meta-analysis using a random-effects model was used to estimate pooled sensitivity and specificity for discriminating benign from malignant. We reviewed evidence for followup strategies for masses considered benign, and for adverse outcomes of diagnostic surgery. We also reviewed published models of the natural history of ovarian cancer and compared the impact of assumptions about natural history on outcomes. RESULTS: The majority of studies did not describe whether patients presented with asymptomatic masses detected through screening or with symptoms. Prevalence of malignant masses in a U.S. postmenopausal screening population was approximately 0.1 percent, while benign masses were found in 0.8 to 1.8 percent of women. Pooled (a) sensitivity and (b) specificity were: bimanual exam (a) 0.45, (b) 0.90; ultrasound morphology scores (a) 0.86 to 0.91, (b) 0.68 to 0.83; Doppler resistive index (a) 0.72, (b) 0.90; pulsatility index (a) 0.80, (b) 0.73; maximum systolic velocity (a) 0.74, (b) 0.81; presence of vessels (a) 0.88, (b) 0.78; combined morphology and Doppler (a) 0.86, (b) 0.91; MRI (a) 0.91, (b) 0.88; CT (a) 0.90, (b) 0.75; FDG-PET (a) 0.67, (b) 0.79; and CA 125 (a) 0.78, (b) 0.78. Both sensitivity and specificity of CA-125 were better in postmenopausal than in premenopausal women. In modeled outcomes, combinations of imaging and CA-125 were both more sensitive and more specific than either alone. Performance of scoring systems in validation studies was consistently worse than in development studies; the highest demonstrated specificity observed was 0.91, with a concurrent sensitivity of 0.74. Evidence on followup strategies was sparse, although one large study provided good evidence for safely following unilocular cysts less than 10 cm in diameter. Overall complication rates in studies of surgically managed adnexal masses were low, but important clinical information was not reported. CONCLUSIONS: All diagnostic modalities showed trade offs between sensitivity and specificity, but the available literature does not provide sufficient detail on relevant characteristics of study populations to allow confident estimation of the results of alternative diagnostic strategies. Although modeling studies may prove useful in evaluating diagnostic algorithms, further work is needed to explore the implications of uncertainty about the natural history of ovarian cancer. PMID- 17854239 TI - Longer time to antipsychotic treatment discontinuation for any cause is associated with better functional outcomes for patients with schizophrenia, schizophreniform disorder, or schizoaffective disorder. AB - OBJECTIVE: Time to all-cause treatment discontinuation is considered a composite proxy measure of treatment efficacy, safety, and tolerability. Longer time to discontinuation of antipsychotic medication for any cause has been shown to be associated with greater symptom improvements in the treatment of schizophrenia. This study examines whether longer time to all-cause medication discontinuation is also linked to better functional outcomes. METHOD: Using pooled data from 4 randomized, double-blind antipsychotic trials of 24- to 28-weeks' duration, this study examined the association between time to all-cause treatment discontinuation and functional outcomes, as assessed by a disease-specific, clinician-rated measure (Quality of Life Scale [QLS]) and a generic, patient reported measure (Medical Outcomes Study Short Form 36 [SF-36]). Patients in these trials had a DSM-IV diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder. This post hoc analysis used Pearson partial correlations to assess relationships between time to treatment discontinuation and changes in functional scores, adjusting for baseline scores. Repeated measures analyses were also conducted to compare post-baseline functional outcome change over time between completers and noncompleters. RESULTS: Longer time to all-cause treatment discontinuation was found to be significantly associated with greater improvements in all assessed functional domains (p < .05). Patients who completed their respective trials (46.8%, 761/1627) experienced significantly greater improvement in functional outcome measures (in 4 QLS domains and SF-36 mental health component summary score; all, p < .001) compared to patients who discontinued for any cause. In addition, greater symptom improvement was significantly associated with greater functional improvements in assessed domains. CONCLUSIONS: Findings from this post hoc analysis illustrate the importance of longer treatment duration with antipsychotics for improving functional outcomes in the treatment of patients with schizophrenia. PMID- 17854240 TI - Adherence to pharmacotherapy in bipolar disorder patients with and without co occurring substance use disorders. AB - OBJECTIVE: To examine patterns of adherence to mood stabilizers and reasons for nonadherence in patients with bipolar disorder, with and without substance use disorder (SUD). METHOD: From December 2003 to October 2004, 115 patients with DSM IV-diagnosed bipolar disorder (58 with SUD and 57 without SUD) were administered a structured interview regarding their lifetime experience with mood stabilizers. RESULTS: Lifetime adherence with mood stabilizers for the SUD group was 65.5%, versus 82.5% for the non-SUD group (p < .05). Lifetime lithium adherence for the SUD group was lower than for the non-SUD group (65.9% vs. 85.0%, p < .05). Substance-related reasons were more commonly cited by the SUD group than the non SUD group. In contrast, pill- and dosage-related reasons were more frequently endorsed by the non-SUD group than the SUD group. CONCLUSION: In bipolar disorder patients, those with co-occurring SUD were less adherent than those without SUD. The SUD group was also less adherent to lithium than the non-SUD group. The reasons for nonadherence differed by presence or absence of a SUD. Physicians should be alert to these differences in their clinical practices while prescribing medications. PMID- 17854241 TI - Lithium augmentation compared with phenelzine in treatment-resistant depression in the elderly: an open, randomized, controlled trial. AB - BACKGROUND: Up to a third of elderly patients with major depressive disorder do not respond to a first course of treatment with an antidepressant. There is a lack of controlled studies evaluating therapies for treatment-resistant depression in late-life depression, and no randomized controlled studies assessing the efficacy and tolerability of lithium augmentation in elderly patients have been published. METHOD: Twenty-nine elderly inpatients with major depressive disorder according to DSM-IV criteria who had previously failed to respond to 1 or more adequate trials with a tricyclic antidepressant or venlafaxine were included in a 6-week, open, randomized, controlled study with a 2-year follow-up. Subjects received either lithium augmentation or the monoamine oxidase inhibitor phenelzine. The primary outcome criterion was remission, defined as a final score of less than or equal to 10 on the Montgomery-Asberg Depression Rating Scale (MADRS). Response was defined as at least 50% reduction on the MADRS or the Hamilton Rating Scale for Depression (HAM-D). RESULTS: Twenty eight subjects completed the trial. Remission on the MADRS was achieved by 33.3% of the lithium patients, compared with none of the phenelzine patients (p = .042). Response also showed a difference in favor of lithium augmentation (p = .035 on both the MADRS and the HAM-D). Overall tolerability was good, with no dropouts due to side effects. Subjective memory impairment was more prevalent among patients receiving phenelzine (p = .002), and tremors were significantly more prevalent among patients receiving lithium (p = .002). During the 2-year follow-up, 25 patients (86.2%) did achieve remission, particularly on prolonging the lithium treatment (5 patients) or on lithium augmentation to phenelzine (5 patients). CONCLUSION: Lithium was more effective than phenelzine in elderly patients with treatment-resistant major depressive disorder, while tolerance of both treatments was remarkably good in this group of elderly inpatients with many comorbid medical disorders. CLINICAL TRIALS REGISTRATION: Controlled-trials.com identifier is RCTN93105957. PMID- 17854242 TI - Cognitive functioning and acute sedative effects of risperidone and quetiapine in patients with stable bipolar I disorder: a randomized, double-blind, crossover study. AB - OBJECTIVE: Antipsychotic medications differ in their sedative potential, which can affect cognitive performance. The primary objective of this double-blind study was to compare the effects of treatment initiation with risperidone and quetiapine on cognitive function in subjects with stable bipolar disorder. METHOD: Subjects had a DSM-IV diagnosis of bipolar I disorder in partial or full remission and a Young Mania Rating Scale score .40 for all other comparisons). CONCLUSIONS: Among people treated for bipolar disorder, modest changes in severity of depression are associated with statistically and clinically significant changes in functional impairment and disability. In contrast, changes in severity of mania or hypomania are not consistently associated with differences in functioning. Conventional measures of functioning, however, may not be sensitive to the effects of mania symptoms. PMID- 17854250 TI - The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) Study: Outcomes from the 2-year and combined maintenance phases. AB - OBJECTIVE: To report second-year results from the 2-year maintenance phase of a long-term study to evaluate the efficacy and safety of venlafaxine extended release (ER) in preventing recurrence of depression. METHOD: Outpatients with recurrent unipolar depression (DSM-IV criteria; N = 1096) were randomly assigned in a 3:1 ratio to 10 weeks of treatment with venlafaxine ER or fluoxetine. Responders (17-item Hamilton Rating Scale for Depression [HAM-D(17)] total score or= 50% decrease from baseline) entered a 6-month, double-blind continuation phase on the same medication. Continuation-phase responders were enrolled into maintenance treatment consisting of 2 consecutive 12-month phases. At the start of each maintenance phase, venlafaxine ER responders were randomly assigned to receive double-blind treatment with venlafaxine ER or placebo, and fluoxetine responders were continued for each period. The second 12-month maintenance phase compared the time to recurrence of depression with venlafaxine ER (75 to 300 mg/day) versus placebo as the primary efficacy measure. The primary definition of recurrence was a HAM-D(17) total score > 12 and < 50% reduction from baseline (acute phase) at 2 consecutive visits or at the last valid visit prior to discontinuation. The time to recurrence was evaluated using Kaplan-Meier methods and compared between the venlafaxine ER and placebo groups using log-rank tests. Secondary outcome measures included rates of response and remission (defined as HAM-D(17) 350 msec) were found that would reflect the semantic modulation in this nonattend passive design, indicating the possible role of attention in generating the later responses. Our results suggest that the earliest brain processes of semantic context integration can occur at approximately 100 msec after the onset of spoken words in the left inferior frontal and superior temporal cortex. PMID- 17854282 TI - Rapid onset relational memory effects are evident in eye movement behavior, but not in hippocampal amnesia. AB - Little is known about the mechanisms by which memory for relations is accomplished, or about the time course of the critical processes. Here, eye movement measures were used to examine the time course of subjects' access to and use of relational memory. In four experiments, participants studied faces superimposed on scenic backgrounds and were tested with three-face displays superimposed on the scenes viewed earlier. Participants exhibited disproportionate viewing of the face originally studied with the scene, compared to other equally familiar faces in the test display. When a preview of a previously viewed scene was provided, permitting expectancies about the to-be presented face to emerge, disproportionate viewing was manifested within 500-750 msec after test display onset, more than a full second in advance of explicit behavioral responses, and occurred even when overt responses were not required. In the absence of preview, the viewing effects were delayed by approximately 1 sec. Relational memory effects were absent in the eye movement behavior of amnesic patients with hippocampal damage, suggesting that these effects depend critically on the hippocampal system. The results provide an index of memory for face-scene relations, indicate the time by which retrieval and identification of these relations occur, and suggest that retrieval and use of relational memory depends critically on the hippocampus and occurs obligatorily, regardless of response requirements. PMID- 17854283 TI - Neglected time: impaired temporal perception of multisecond intervals in unilateral neglect. AB - Recent neuroimaging and neuropsychological studies have suggested that the right hemisphere, particularly frontal regions, is important for the perception of the passage of time. We examined the ability to estimate durations of up to 60 sec in a group of eight patients with unilateral neglect. When estimating multisecond intervals, neglect patients grossly underestimated all durations. On average, healthy controls (HC) demonstrated reasonably accurate estimates of all durations tested. Although the right hemisphere lesioned control patients without neglect also tended to underestimate durations, these underestimations were significantly better than the performance of the neglect group. These findings suggest a pivotal role for a right hemisphere fronto-parietal network in the accurate perception of multisecond durations. Furthermore, these findings add to a growing body of literature suggesting that neglect cannot be understood simply in terms of a bias in orienting attention to one side of space. Additional deficits of the kind demonstrated here are likely to be crucial in determining the nature and extent of the loss of conscious awareness for contralesional events. PMID- 17854284 TI - Spontaneous inferences, implicit impressions, and implicit theories. AB - People make social inferences without intentions, awareness, or effort, i.e., spontaneously. We review recent findings on spontaneous social inferences (especially traits, goals, and causes) and closely related phenomena. We then describe current thinking on some of the most relevant processes, implicit knowledge, and theories. These include automatic and controlled processes and their interplay; embodied cognition, including mimicry; and associative versus rule-based processes. Implicit knowledge includes adult folk theories, conditions of personhood, self-knowledge to simulate others, and cultural and social class differences. Implicit theories concern Bayesian networks, recent attribution research, and questions about the utility of the disposition-situation dichotomy. Developmental research provides new insights. Spontaneous social inferences include a growing array of phenomena, but they have been insufficiently linked to other phenomena and theories. We hope the links suggested in this review begin to remedy this. PMID- 17854285 TI - Personnel selection. AB - We review developments in personnel selection since the previous review by Hough & Oswald (2000) in the Annual Review of Psychology. We organize the review around a taxonomic structure of possible bases for improved selection, which includes (a) better understanding of the criterion domain and criterion measurement, (b) improved measurement of existing predictor methods or constructs, (c) identification and measurement of new predictor methods or constructs, (d) improved identification of features that moderate or mediate predictor-criterion relationships, (e) clearer understanding of the relationship between predictors or between predictors and criteria (e.g., via meta-analytic synthesis), (f) identification and prediction of new outcome variables, (g) improved ability to determine how well we predict the outcomes of interest, (h) improved understanding of subgroup differences, fairness, bias, and the legal defensibility, (i) improved administrative ease with which selection systems can be used, (j) improved insight into applicant reactions, and (k) improved decision maker acceptance of selection systems. PMID- 17854287 TI - Emotional support for men and women with cancer: do patients receive what their partners provide? AB - OBJECTIVES: In the context of mainly gastrointestinal cancer surgery, the study examines the course of spousal support in 173 dyads over half a year to illuminate the function of gender in support transactions. METHOD: Provided and received emotional support were assessed in 108 male patient/female partner couples and 65 female patient/male partner couples. Using the Berlin Social Support Scales, assessments took place during the week before cancer surgery, 1 month, and 6 months after cancer surgery. RESULTS: Gender differences emerged for support received and provided. Support received from partners was initially high for all patients, remained high over time for men, but decreased for women. Provided support decreased for male partners, but remained high in female partners. The effects were of medium size. Patients' received support was reflected by partners' reports of support provided. Women who reported received support 6 months after surgery had partners who had reported support provision 5 months earlier. CONCLUSIONS: Alternative sources of support, in particular for women, such as their network of friends or professional help, may need to be identified. A couple-coping intervention could be implemented to help partners learn about each other's needs in times of crisis and ways to cope with adversity. PMID- 17854286 TI - The mind and brain of short-term memory. AB - The past 10 years have brought near-revolutionary changes in psychological theories about short-term memory, with similarly great advances in the neurosciences. Here, we critically examine the major psychological theories (the "mind") of short-term memory and how they relate to evidence about underlying brain mechanisms. We focus on three features that must be addressed by any satisfactory theory of short-term memory. First, we examine the evidence for the architecture of short-term memory, with special attention to questions of capacity and how--or whether--short-term memory can be separated from long-term memory. Second, we ask how the components of that architecture enact processes of encoding, maintenance, and retrieval. Third, we describe the debate over the reason about forgetting from short-term memory, whether interference or decay is the cause. We close with a conceptual model tracing the representation of a single item through a short-term memory task, describing the biological mechanisms that might support psychological processes on a moment-by-moment basis as an item is encoded, maintained over a delay with some forgetting, and ultimately retrieved. PMID- 17854288 TI - Testosterone regulation of homocysteine metabolism modulates redox status in human prostate cancer cells. AB - Clearance of homocysteine via the transsulfuration pathway provides an endogenous route for cysteine synthesis and represents a quantitatively significant source of this amino acid needed for glutathione synthesis. Men have higher plasma levels of total homocysteine than do women, but the mechanism of this sex dependent difference is not known. In this study, we investigated regulation by testosterone of cystathionine beta-synthase (CBS), which catalyzes the committing step in the transsulfuration pathway. We report that testosterone downregulates CBS expression via a posttranscriptional mechanism in the androgen-responsive prostate cancer cell line, LNCaP. This diminution in CBS levels is accompanied by a decrease in flux through the transsulfuration pathway and by a lower intracellular glutathione concentration. The lower antioxidant capacity in testosterone-treated prostate cancer cells increases their susceptibility to oxidative stress conditions. These results demonstrate regulation of the homocysteine-clearing enzyme, CBS, by testosterone and suggest the potential utility of targeting this enzyme as a chemotherapeutic strategy. PMID- 17854289 TI - Assessment of the results of treatment in individual units through benchmarking of data. PMID- 17854290 TI - Strictureplasty vs resection in small bowel Crohn's disease: an evaluation of short-term outcomes and recurrence. AB - AIM: To compare postoperative adverse events and recurrence following strictureplasty or bowel resection in patients with small bowel Crohn's disease (CD). METHOD: A literature search was performed to identify studies published between 1980 and 2006 comparing outcomes of CD patients undergoing either strictureplasty or bowel resection. Hazard ratios were calculated from Kaplan Meier plots of cumulative recurrence data. Quality assessment of the included studies was performed. Random-effect meta-analytical techniques were employed. Sensitivity analysis and assessment of heterogeneity were performed. RESULTS: Seven studies comprising 688 CD patients (strictureplasty n = 311, 45%; resection with or without strictureplasty n = 377, 55%) were included. Patients undergoing strictureplasty alone had a lower risk of developing postoperative complications than those who underwent resection (OR = 0.60, 95% CI: 0.31-1.16) although this was not statistically significant (P = 0.13). Surgical recurrence after strictureplasty was more likely than after resection (OR = 1.36, 95% CI: 0.96 1.93, P = 0.09). Patients who had a resection had a significantly longer recurrence-free survival than those undergoing strictureplasty alone (HR = 1.08, 95% CI: 1.02-1.15, P = 0.01). CONCLUSION: Patients with small bowel CD undergoing strictureplasty alone may have fewer postoperative complications than those undergoing a concomitant bowel resection. However, surgical recurrence maybe higher following strictureplasty alone than with a concomitant small bowel resection. Patients may require appropriate preoperative counselling regarding the pros and cons of each operative technique. PMID- 17854291 TI - Laparoscopic colorectal surgery - results from 200 patients. AB - OBJECTIVE: Laparoscopic surgery is increasingly being performed for benign and malignant colorectal disease. This study examines the short-term results in a consecutive series of laparoscopic colorectal procedures performed over 2 years. METHOD: A prospective database was established for all elective patients undergoing laparoscopic colorectal surgery by one surgeon. The main outcome measures assessed were operative duration, conversion rate, length of hospital stay, morbidity and mortality and lymph node harvest. RESULTS: Two hundred and thirty-one consecutive patients were referred for elective colorectal surgery, with 18 patients excluded from laparoscopic surgery. Thirteen patients had nonresective laparoscopic colorectal procedures for endometriosis and have been excluded from the series. Of 200 patients who underwent a laparoscopic colorectal procedure, 114 (57%) were female, the median age was 67 years (inter-quartile range (IQR) 57-76), and there were 116 malignancies. The most common operations were anterior resection and sigmoid colectomy (n = 82), right hemicolectomy (n = 62) and left hemicolectomy (n = 12). The median operating time was 120 min (IQR 90-150) and 10 patients (5%) required conversion to open surgery. The median lymph node harvest in malignancies was 21 nodes (IQR 15-30) and no positive resection margins were found. There were two deaths and 29 significant complications (14.5%), with seven patients requiring re-operations because of postoperative complications. The median postoperative hospital stay was 4 days (IQR 3-6) and 13 patients (6.5%) were re-admitted within 30 days of hospital discharge. CONCLUSION: Laparoscopic colorectal surgery is possible for most benign and malignant conditions, with low conversion and complication rates, as well as short hospital stay. PMID- 17854292 TI - Inter general practice variability in use of referral guidelines for colorectal cancer. AB - OBJECTIVE: The Two-Week Wait (TWW) referral system for suspected colorectal cancers has a low yield. To examine this, we assessed the referral pattern of general practices within four primary care trusts and looked at the variability of yield of colorectal cancer amongst all TWW referrals and assessed the reasons for variability. METHOD: A prospectively collected database of all colorectal cancers was examined for new cases diagnosed in the 12 months from April 1st 2004. Patients were cross-referenced via general practitioner (GP) codes to identify the referral origin. Reasons for the variability in referral patterns from each general practice were assessed in relation to TWW referrals, population demographics and through postal questionnaire of GPs. RESULTS: A total of 175 patients diagnosed with colorectal cancer were referred from 49 general practices. Whilst there was a positive correlation between the number of TWW referrals and colorectal cancer per 1000-practice population (P = 0.001; Spearman correlation coefficient r(s=0.447,) two-tailed), there was a big discrepancy between referrals and cancer diagnosed in many general practices. Twenty-six general practices (53%) had no colorectal cancer diagnosed via the TWW route and these practices had significantly lower utilization of the TWW referral pathway. In the postal survey, 22% of GPs were unaware of TWW clinics or colorectal cancer referral guidelines and only 8% of GPs knew the number of referral criteria. CONCLUSION: This study demonstrates wide variability within primary care, in the appropriate use of colorectal cancer referral guidelines. General practices should be targeted for education. PMID- 17854293 TI - Is anaemia relevant in the referral and diagnosis of colorectal cancer? AB - OBJECTIVE: Current efforts to improve the outcome from colorectal cancer aim to shorten the delay between referral and diagnosis. Investigation of iron deficiency anaemia has a high yield for the diagnosis of gastrointestinal malignancy and its presence is included in current referral guidelines. We explored the relationship between anaemia and colorectal cancer. METHOD: We reviewed hospital and laboratory database records of patients diagnosed with colorectal cancer between January 2003 and June 2004. The site of colorectal cancer was correlated with the presence of anaemia at the time of referral. Anaemia was defined according to local practice (Hb < 12.0 g/dl in females and <13.0 g/dl in males), compared with the threshold recommended in current national referral guidelines (Hb < 10 g/dl in females and <11 g/dl in males). RESULTS: Over 18 months, 143 patients were diagnosed with colorectal cancer. Anaemia was present in 48% of males and 50% of females using local practice and 24% of males and 16% of females using national referral guidelines. Those with right-sided and non-rectal cancers were significantly more likely to be anaemic than those with left-sided and rectal cancers, respectively. CONCLUSION: In approximately half of cases the diagnosis of colorectal cancer is not associated with anaemia. Anaemia is more common with proximal lesions but this is not a consistent finding. The current threshold for anaemia at which national guidelines suggest referral also appears to be insensitive. PMID- 17854294 TI - Surgery for fistula-in-ano: an audit of practise of colorectal and general surgeons. AB - OBJECTIVE: Some conditions, previously managed by general surgeons, may be treated more successfully by colorectal specialists. This argument is well established for rectal cancer but does it also apply to benign conditions? This study compares the treatment strategies and outcomes for fistulae-in-ano by general and colorectal surgeons in a district general hospital. METHOD: Patients who had surgery for fistula-in-ano from January 1992-October 2003 were identified from theatre records. Case notes were reviewed for data on type of fistula, aetiology, surgery performed and recurrence. All patients were sent a questionnaire requesting details of recurrence and incontinence. The severity of incontinence was assessed using the Faecal Incontinence Quality of Life Scale (FIQOLS) and the Faecal Incontinence Severity Index (FISI). RESULTS: Eighty four patients (male = 53) were identified. Colorectal surgeons performed surgery in 34 and general surgeons in 50 patients. These groups were comparable with terms of age, gender, aetiology (colorectal: IBD = 5, cryptoglandular = 21: general IBD = 14, cryptoglandular = 24; P = 0.28; Chi-squared test), and type of fistulae (colorectal: inter-sphincteric = 20, trans-sphincteric = 13: general inter sphincteric = 30, trans-sphincteric = 18: P = 1.0; Fisher's exact test). Colorectal surgeons carried out fewer fistulotomies (47.1%vs 84.0%; P < 0.001; Fisher's exact test), more staged fistulotomies with Setons (44.1%vs 10.0%: P < 0.001; Fisher's exact test), and had fewer recurrences (9.7%vs 30.0%: P < 0.05; Fisher's exact test) when compared with general surgeons. Five patients with recurrence from the general surgery group were subsequently referred to the colorectal surgeons; four patients had further surgery (fistulotomy = 2; staged fistulotomy = 2) with no recurrence to date; one patient required proctectomy. Forty seven (64.4%) patients answered the questionnaire. There was no difference between patients operated on by colorectal or general surgeons with regards the frequency (43.5%vs 62.5%: P = 0.25; Fisher's exact test) or severity [FISI 26 (21 38); median (inter-quartile range) vs 26 (17-38); median (inter-quartile range: P = 0.85; Mann-Whitney test) of faecal incontinence. There was no difference between the groups with regards any of the four scales that comprised the FIQOLS. CONCLUSIONS: The number of included patients is far too low to draw any conclusions but there were some interesting trends. For similar patient samples, colorectal surgeons seem to adopt a more conservative approach and have fewer recurrences than general surgeons. These differences are not reflected in the frequency or severity of postoperative incontinence. PMID- 17854295 TI - Closure of temporary stoma after anterior resection. PMID- 17854296 TI - All 'enhanced-recovery' protocols are not created equal. PMID- 17854301 TI - Avascular necrosis of the femoral head in childhood chronic myeloid leukaemia. PMID- 17854302 TI - Beta-thalassaemia and sickle cell anaemia as paradigms of hypercoagulability. AB - Thalassaemia and sickle cell disease (SCD) represent the most common forms of hereditary haemolytic anaemia and result from a partial or complete lack of synthesis of one of the major alpha- or beta-globin chains of haemoglobin A or from a single amino acid mutation (beta(6Glu-->Val)) of the beta-globin chain respectively. Although they have different pathophysiologies, patients with these conditions manifest both biochemical and clinical evidence of hypercoagulability. While the frequency of various thrombotic complications may vary in beta thalassaemia and homozygous SCD [sickle cell anaemia (SCA)], patients with both diseases manifest decreased levels of natural anticoagulant proteins, as well as increased markers of thrombin generation and platelet activation. The abnormal phospholipid membrane assymetry present in the red blood cells of beta thalassaemia and SCA patients, with resultant phosphatidylserine exposure appears to play a significant role in the aetiology of the observed hypercoagulable state. This review presents the available data on the aetiology and clinical manifestations of the coagulation and platelet activation that exist in both beta thalassaemia and SCA, as well as the potential therapeutic implications resulting from this hypercoagulability. PMID- 17854303 TI - Trepanning or trephines: a history of bone marrow biopsy. AB - Trepanning of bone is the oldest known procedure carried out by man and yet it is only in the last 100 years that we have made use of the technique to diagnose and treat haematological disorders. These advances have been made possible by improvements in instruments, techniques, anaesthesia, laboratory processing and the expertise of haematologists to report the specimens. With the advent of immunological markers and molecular biology, the need for quality bone marrow specimens, if anything, has increased. It will be many years before the bone marrow aspiration/trephine procedure is relegated to the annals of history. PMID- 17854304 TI - Genetic alterations determine chemotherapy resistance in childhood T-ALL: modelling in stage-specific cell lines and correlation with diagnostic patient samples. AB - Acquired drug resistance eventually leads to treatment failure in T-cell acute lymphoblastic leukaemia (T-ALL). Immunophenotypic and cytogenetic heterogeneities within T-ALL influence susceptibility to cytotoxic therapy, and little is known about the mechanisms of drug resistance at specific stages of T-cell ontogeny. We developed tolerance to therapeutic concentrations of daunorubicin (DNR) and L asparaginase (L-asp) in Jurkat (CD1a(-), sCD3(+)) and Sup T1 (CD1a(+), sCD3(-)) cell lines, having respective 'mature' and 'cortical' stages of developmental arrest. DNR resistant cells acquired multidrug resistance: 310-fold increased resistance to vincristine (VCR) and a 120-fold increased resistance to prednisolone (PRED). Microarray analysis identified upregulation of asparagine synthetase (ASNS) and argininosuccinate synthase 1 (ASS1) to cell lines with acquired resistance to L-asp, and in the case of DNR, upregulation of ATP-binding cassette B1 (ABCB1). Suppression of ABCB1, ASNS and ASS1 by RNA interference revealed their functional relevance to acquired drug resistance. Expression profiling of these genes in 80 T-ALL patients showed correlation with treatment response. This study expands the pool of available drug resistant cell lines having cortical and mature stages of developmental arrest, introduces three new drug resistant T-ALL cell lines, and identifies gene interactions leading to L asp and DNR resistance. PMID- 17854305 TI - Connective tissue growth factor is an indicator of bone involvement in multiple myeloma, but matrix metalloproteinase-9 is not. AB - Bone disease (BD) in multiple myeloma (MM) is because of the activation of osteoclasts and impairment of osteoblast differentiation. Connective tissue growth factor (CTGF) is known to participate in the differentiation of mesenchymal stem cells to committed osteoprogenitor cells. We analysed the concentration of circulating CTGF in 35 MM patients and 22 malignant lymphoma (ML) patients and 14 normal individuals. CTGF is protease-sensitive and thus is found as both an N-terminal half fragment (N-half CTGF) and whole (W-CTGF). Serum levels of W-CTGF and N-half CTGF + W-CTGF were determined by separate sandwich enzyme-linked immunosorbent assays. The level of W-CTGF was significantly lower (P < 0.005) in MM patients compared with ML patients and normal individuals, while N-half + W-CTGF was similar in all groups. Furthermore, W-CTGF was significantly lower in MM patients with BD compared with those without BD (P < 0.005) and this was independent of previous treatment. Matrix metalloproteinase (MMP)-9 is produced by myeloma cells and is thought to be related to BD in MM. However, MMP-9 does not cleave CTGF and serum MMP-9 level was not related to BD in MM. Thus, CTGF is an indicator of BD in MM; its metabolism and function in MM should be clarified. PMID- 17854306 TI - Chromosome 1p21 deletion is a novel prognostic marker in patients with multiple myeloma. AB - The combination of fluorescence in situ hybridization with cytoplasmic light chain detection identified chromosome 1p21 deletion in 18 (20%) of 87 patients with multiple myeloma. 1p21 deletion was associated with higher serum calcium level, 13q deletion, and t(4;14). Patients with 1p21 deletions had a significantly shorter progression-free survival (PFS) (median 10.5 vs. 22.3 months, P = 0.0002) and shorter overall survival (OS) (median 33.9 months vs. not reached, P = 0.002) than those without 1p21 deletions. On multivariate analysis, which included deletions of 13q, TP53, t(4;14) and CKS1B amplification, 1p21 deletion remained as an independent risk factor for PFS (P = 0.01) and OS (P = 0.04). PMID- 17854307 TI - Targeting MEK1/2 blocks osteoclast differentiation, function and cytokine secretion in multiple myeloma. AB - Osteolytic bone disease in multiple myeloma (MM) is associated with upregulation of osteoclast (OCL) activity and constitutive inhibition of osteoblast function. The extracellular signal-regulated kinase 1/2 (ERK1/2) pathway mediates OCL differentiation and maturation. We hypothesized that inhibition of ERK1/2 could prevent OCL differentiation and downregulate OCL function. It was found that AZD6244, a mitogen-activated or extracellular signal-regulated protein kinase (MEK) inhibitor, blocked OCL differentiation and formation in a dose-dependent manner, evidenced by decreased alphaVbeta3-integrin expression and tartrate resistant acid phosphatase positive (TRAP+) cells. Functional dentine disc cultures showed inhibition of OCL-induced bone resorption by AZD6244. Major MM growth and survival factors produced by OCLs including B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL), as well as macrophage inflammatory protein (MIP-1alpha), which mediates OCL differentiation and MM, were also significantly inhibited by AZD6244. In addition to ERK inhibition, NFATc1 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1) and c-fos were both downregulated, suggesting that AZD6244 targets a later stage of OCL differentiation. These results indicate that AZD6244 inhibits OCL differentiation, formation and bone resorption, thereby abrogating paracrine MM cell survival in the bone marrow microenvironment. The present study therefore provides a preclinical rationale for the evaluation of AZD6244 as a potential new therapy for patients with MM. PMID- 17854308 TI - JAK2-V617F mutation analysis of granulocytes and platelets from patients with chronic myeloproliferative disorders: advantage of studying platelets. AB - There have been conflicting reports over the JAK2-V617F mutation status of platelets in chronic myeloproliferative diseases (CMPDs). The aim of this study was to analyse JAK2-V617F status, not only in granulocytes but also in platelets. The JAK2-V617F mutation was analysed in both granulocytes and platelets in 115 patients with CMPDs using direct sequencing. JAK2-V617F was detected in granulocytes from 71 of those patients, all 71 of whom also had platelet JAK2 V617F expression. The remaining 44 patients showed negative JAK2-V617F expression on granulocytes, but positive JAK2-V617F expression was detected on the platelets from nine of the 33 essential thrombocythaemia (ET) patients, one of the eight polycythaemia vera patients, and two of the three primary myelofibrosis patients. When ET patients were divided into three groups according to granulocyte and platelet JAK2-V617F status (both-positive, platelets-only positive and both negative), the both-positive and platelets-only positive groups shared the clinical features of higher white blood cell count and frequent thrombosis. These results suggest that analysis of platelets is a more sensitive approach for detecting JAK2-V617F in CMPD patients than analysis of granulocytes. They also suggest that previous reports of the incidence of JAK2-V617F in CMPD patients, obtained using only analysis of granulocytes, could be underestimations. PMID- 17854309 TI - Reduced-intensity conditioning for allogeneic haematopoietic stem cell transplantation in relapsed and refractory Hodgkin lymphoma: impact of alemtuzumab and donor lymphocyte infusions on long-term outcomes. AB - The introduction of reduced-intensity conditioning (RIC) has enabled the role of allogeneic transplantation to be re-evaluated in Hodgkin lymphoma (HL). While T cell depletion reduces graft-versus-host disease (GvHD), it potentially abrogates graft-versus-tumour activity and increases infective complications. We compared the results in 67 sibling donor transplantations following RIC in multiply relapsed patients from two national phase II studies conditioned with fludarabine/melphalan. One used cyclosporine/alemtuzumab (MF-A, n = 31), the other used cyclosporine/methotrexate (MF, n = 36) as GvHD prophylaxis. There was a small excess of chemorefractory cases in the MF cohort (P = NS). MF-A resulted in significantly lower incidences of non-relapse mortality, acute and chronic GvHD, but no significant excess of relapse/progression. Post donor lymphocyte infusion (DLI) disease responses occurred in 8/14 (57%) and 6/11 (55%) patients in the MF-A and MF groups, respectively. Current progression-free survival (CPFS) was superior with MF-A (univariate analysis), with durable responses to DLI contributing to the favourable outcome (43% vs. 25%, P = 0.0356). Disease status at transplantation significantly influenced overall survival (P = 0.0038) and CPFS (P = 0.0014), retaining significance in multivariate analyses, which demonstrated a trend towards improved CPFS with T-cell depletion (P = 0.0939). These data suggest that alemtuzumab significantly reduced GvHD without resulting in a deleterious impact on survival outcomes following RIC in HL, and that durable responses to DLI may be more common following the inclusion of alemtuzumab in the conditioning protocol. PMID- 17854310 TI - CD4(+) T-cell responses to Epstein-Barr virus (EBV) latent membrane protein 1 in infectious mononucleosis and EBV-associated non-Hodgkin lymphoma: Th1 in active disease but Tr1 in remission. AB - Primary infection with Epstein-Barr virus (EBV) in childhood is usually asymptomatic, whereas infection in adolescence may result in infectious mononucleosis (IM) often followed by a fatigue syndrome. EBV latent membrane protein 1 (LMP1) is expressed in latency and in many EBV-associated tumours, including non-Hodgkin lymphoma (NHL). Given the regulatory nature of the CD4(+) T cell response against LMP1 previously reported in healthy donors, we investigated whether patients with active EBV-driven disease can nevertheless mount effector [T-helper cell, type 1 (Th1)] anti-LMP1 responses. We therefore performed a longitudinal study of the nature of CD4(+) T-cell responses to LMP1 in four patients with IM, and five patients with NHL. In both groups, responses changed with time. During symptomatic infection or active tumour growth, responses were dominated by a Th1 effector phenotype, but switched to a regulatory interleukin 10 response upon recovery. In addition, the fine specificities of the T cells driving these responses evolved. This study showed the dynamic nature of CD4(+) T cell responses to LMP1, and demonstrated that, although patients can mount Th1 effector responses, recovery from IM and NHL is associated with regulatory responses. PMID- 17854311 TI - Low-dose oral fludarabine plus cyclophosphamide as first-line treatment in elderly patients with indolent non-Hodgkin lymphoma. AB - Twenty-five elderly patients with untreated indolent non-Hodgkin lymphoma were treated with oral fludarabine 25 mg/m(2)/d (40 mg total dose) and cyclophosphamide 150 mg/m(2)/d, both for four consecutive days, repeated every 28 d for four cycles. In all, 21 (84%) patients were responsive: 10 patients achieved complete remission while partial response was obtained in 11. During an observation period of 37 months, there was an overall survival rate of 70% and a median event-free survival of 20 months. Haematological and extra-haematological toxicity were mild. This reduced-dose Flu-based oral regimen showed good efficacy and was simple to administer on an outpatient basis. PMID- 17854312 TI - FUS expression alters the differentiation response to all-trans retinoic acid in NB4 and NB4R2 cells. AB - The FUS gene is overexpressed in acute myeloid leukaemia (AML) patients and has roles in transcription and mRNA processing. We used ectopic expression of FUS and FUS antisense sequences to assess the effect of modulation of FUS expression in all-trans retinoic acid (ATRA)-sensitive (NB4) and insensitive (NB4R2) human acute promyelocytic (APL) cell lines which express the t(15:17) translocation. Growth, viability and differentiation patterns were maintained, but the expression of the FUS antisense construct in both the cell lines altered the response to ATRA: the previously ATRA-sensitive NB4 cells exhibited resistance; whilst the previously resistant NB4R2 cells showed a differentiation response to treatment. PMID- 17854313 TI - WASP localizes to the membrane skeleton of platelets. AB - Patients with Wiskott-Aldrich syndrome (WAS), an X-linked blood cell disease, suffer from severe thrombocytopenia due to accelerated loss of defective platelets. The affected gene encodes WASP, an actin regulatory protein thought to reside in the cytoplasm of resting leucocytes. In contrast, this study showed that, for platelets, one-quarter of WASP molecules fractionate in the detergent insoluble high speed pellet characterized as the membrane skeleton, the scaffold structure that underlies the lipid bilayer and stabilizes the surface membrane. Following treatment of platelets with thrombin and stirring, which induces cytoarchitectural remodelling, WASP and other membrane skeletal components sedimented at lower g force and partitioned in the low-speed pellet. Thrombin and stirring also induced WASP tyrosine phosphorylation, a rapid activating reaction, and proteolytic inactivation by cysteine protease calpain. Both the alteration of the sedimentation profile and the proteolytic inactivation were specific for the membrane skeletal pool of WASP and were abrogated in alphaIIb beta3 integrin deficient platelets and in normal platelets treated with an integrin antagonist. The findings demonstrate that WASP is a component of the resting platelet membrane skeleton and participates in membrane skeletal rearrangements downstream of integrin outside-in signalling. The possible implications for the platelet defect in WAS are discussed. PMID- 17854314 TI - Thrombin generation: a comparison of assays using platelet-poor and -rich plasma and whole blood samples from healthy controls and patients with a history of venous thromboembolism. AB - We have developed a whole blood thrombin generation (TG) assay whereby TG is initiated with a low-tissue factor concentration and monitored using a fluorogenic thrombin substrate. Significantly higher values were found in blood samples from 50 patients with a history of venous thromboembolism (VTE) compared with 31 healthy controls (HC), for peak height (P = 0.0034) and endogenous thrombin potential (ETP) (P = 0.0027). Results from 31 VTE patients and the 31 controls in the absence of corn trypsin inhibitor (CTI) showed significantly higher values in the VTE group for peak height (P = 0.0013) and ETP (P = 0.002). In the presence of CTI, significantly higher values were only seen in ETP (P = 0.024). No significant increases in TG were found using platelet poor (PPP) or rich (PRP) plasma with or without CTI. The whole blood TG assay in the absence or presence of CTI showed a higher proportion (25/50 and 12/31, respectively) of raised peak height and/or ETP values than plasma assays (PPP 9/50 and 5/31 respectively and PRP 13/50 and 6/31, respectively). Our results show the whole blood TG assay is more sensitive for determining the increases in TG in patients with a history of VTE than PPP and PRP TG assays. PMID- 17854316 TI - Risk of thromboembolism in 14,000 individuals with coeliac disease. AB - The risk of venous thromboembolism (VTE) was examined in individuals with coeliac disease (CD). The Swedish national inpatient register was used to identify 14 207 individuals with a diagnosis of CD (1964-2003). These individuals were matched for age, sex, calendar year and county with 69 048 reference individuals. Cox regression was used to estimate hazard ratios (HRs) for subsequent thromboembolism in individuals with more than 1 year of follow-up and no prior VTE. CD was associated with an increased risk of subsequent VTE (HR = 1.86; 95% confidence interval (CI) 1.54-2.24). The risk increase was restricted to individuals with CD diagnosed in adulthood. Risk estimates were not affected by the presence of diabetes mellitus or concomitant surgery. Compared with inpatients as reference individuals, CD individuals remained at increased risk of subsequent VTE (adjusted HR = 1.27; 95% CI = 1.06-1.52). In conclusion, this study found a statistically significantly positive association between CD and VTE. This modest association might be explained by a combination of surveillance bias and chronic inflammation. PMID- 17854315 TI - Antiphospholipid antibody syndrome: the flow cytometric annexin A5 competition assay as a diagnostic tool. AB - The mechanism underlying hypercoagulability in antiphospholipid antibody syndrome (APS) is uncertain. Here, we present a flow-cytometric assay (FCA) based on the hypothesis that anti-platelet-anionic-phospholipid autoantibodies (aPL) interfere with the activity of the natural anticoagulant protein annexin A5, thereby accelerating platelet procoagulant activity. This study assessed the clinical utility of the feasible FCA, which demonstrates the competition of the patient's aPL with the binding of annexin A5 to the platelet-anionic-phospholipids, in the diagnosis of APS. Sixty-two (94%) of 66 APS patients, 20 (51%) of 39 patients with systemic lupus erythematosus and two (4%) of 49 healthy individuals were positive by FCA. Compared with the anticardiolipin (aCL) assay, the relative sensitivity was 82% and the specificity 73.3%. However, 19 (25%) aCL-negative patients were positive by FCA; 12 were positive for lupus-anticoagulant (LA). Compared with LA assay, the relative sensitivity was 85% and the specificity 72.2%. However, 21 (26%) LA-negative patients were FCA-positive, 12 were positive for aCL. The FCA was particularly sensitive for APS patients with arterial (97.0%) and gestational vascular complications (100%) with overall sensitivity of 95% and specificity of 97%. Our findings suggest that the FCA is practical, sensitive and specific for the detection of clinically relevant aPL in the diagnosis of APS. PMID- 17854317 TI - Pseudo-exon activation caused by a deep-intronic mutation in the fibrinogen gamma chain gene as a novel mechanism for congenital afibrinogenaemia. AB - Congenital afibrinogenaemia, characterized by severe fibrinogen deficiency, is caused by mutations within FGA, FGB or FGG. Conventional sequencing of coding regions and splice signals of these three genes did not reveal any mutation in an afibrinogenaemic proband. After confirming disease co-segregation with the fibrinogen cluster, full intron sequencing was tackled leading to the identification of a novel transvertion within FGG intron 6 (IVS6-320A-->T). Its effect on mRNA processing was evaluated in-vitro: the in-frame inclusion of a 75 bp pseudo-exon carrying a premature stop was found, representing the first report of pseudo-exon activation as a mechanism leading to afibrinogenaemia. PMID- 17854318 TI - Detection of CD4(+) T-cell antibodies in a patient with idiopathic CD4 T lymphocytopenia and cryptococcal meningitis. AB - Idiopathic CD4(+) T lymphocytopenia (ICL) is defined as a CD4(+) T-cell count <0.3 x 10(9)/l or <20% of the total T-cell count on two occasions in the absence of any immunodeficiency disorder or therapy associated with reduced CD4(+) T-cell count. Although several mechanisms of ICL have been reported, the pathophysiology is still largely unknown. This case report describes a patient who presented with cryptococcal meningitis and was subsequently discovered to meet the criteria for ICL. Flow cytometric analysis of the patient's peripheral blood mononuclear cells revealed antibodies coating a much larger proportion of his CD4(+) T cells (33.61%) than the CD4(+) T cells of normal donors (3.94 +/- 1.77%). The reasons behind the development of these autoantibodies are explored. PMID- 17854320 TI - Platelet refractoriness due to combined anti-HLA and anti-HPA-5a alloantibodies: clinical management during myeloablative allogeneic HSCT and development of a quantitative MAIPA assay. PMID- 17854319 TI - Different regulatory elements are required for response of hepcidin to interleukin-6 and bone morphogenetic proteins 4 and 9. AB - Hepcidin is a major regulator of iron homeostasis. Hepcidin expression is upregulated by inflammatory cytokines, particularly interleukin (IL)-6 and even more potently by the bone morphogenetic proteins 2, 4 and 9 (BMP-2, BMP-4 and BMP 9). This study showed that the regulation of hepcidin expression by IL-6 and BMPs occurs through distinct regulatory elements. The induction of hepcidin by BMPs requires at least two regions of the Hamp1 promoter, one between 140-260 bp and the other between 1.6-2.0 kb upstream of the start of translation. Reporter constructs including 1.6-2.0 kb of the Hamp1 promoter were induced >16-fold by BMPs whereas a 260 bp reporter Hamp1 promoter construct was induced only two- to threefold. The distal 1.6-2.0 kb region appeared to contain several different BMP responsive elements, as incremental lengthening of the promoter construct in this region produced gradual escalation of BMP-responsiveness. In contrast, the IL-6 response required only the proximal 260 bp Hamp1 promoter region. Furthermore, there were no regulatory elements located in the non-coding or coding regions of Hamp1 and activation of the Hamp1 promoter was absent or markedly reduced in cells of non-hepatic origin. PMID- 17854321 TI - Deregulation of a possible tumour suppressor gene, ZC3H12D, by translocation of IGK@ in transformed follicular lymphoma with t(2;6)(p12;q25). PMID- 17854322 TI - A novel regimen incorporating the concomitant administration of fludarabine and alemtuzumab for the treatment of refractory adult acute lymphoblastic leukaemia: a report of three cases. PMID- 17854324 TI - Rituximab in thrombotic microangiopathy. PMID- 17854325 TI - From the fight against alcoholism to 'addictology': shifting the paradigm gives rise to the 'Addictions Management Policy' in France. PMID- 17854326 TI - A safe, sensible and social AHRSE: New Labour and alcohol policy. AB - When the Labour government came to power in the UK in 1997, it took over high and rising levels of alcohol consumption and alcohol-related harm. Contrary to 'old Labour''s views on alcohol policy, New Labour did nothing to reverse this trend, and, if anything, exacerbated it. Since New Labour has been in power, alcohol has become 40% more affordable; consumption has increased by 14% and alcohol-related deaths have increased by over 40%. New Labour viewed alcohol-related harm as a question of individual responsibility and, as expressed in its long awaited 2004 alcohol harm reduction strategy (commonly known as AHRSE), viewed partnerships with the alcohol industry as the solution to reducing harm. Ten years on we have safe, sensible and social, the 3Ss, AHRSE's next steps. On first reading it would seem that the government has learnt nothing from its mistakes of the previous ten years, and in its approach to alcohol policy continues to disable the public interest. Nevertheless, there remain areas where science might inform policy, including health sector policy where there is an emphasis on early diagnosis and treatment, and transport policy, where reducing the legal blood alcohol level to the European Commission maximum recommended level of 0.5g/L is again on the agenda. The 3Ss propose an independent review of the evidence of the relationship between alcohol price, promotion and harm. However, unless this fully reviews the international evidence of the relationship between the economic and physical availability of alcohol, the marketing of alcohol and alcohol related harm, AHRSE and its successor will continue to be a recipe for ineffectiveness. PMID- 17854327 TI - Defining dependence: describing symptom clusters versus central constructs. PMID- 17854328 TI - The future of the alcohol dependence syndrome (ads): possible challenges from more rigorous psychological measurement. PMID- 17854329 TI - The alcohol dependence syndrome: consequences for dsm revisions. PMID- 17854330 TI - We shape our tools, and thereafter our tools shape us: psychiatric epidemiology and the alcohol dependence syndrome concept. PMID- 17854331 TI - Alcohol use disorders in the DSM-V: the task ahead. PMID- 17854333 TI - Analysis of binary outcomes with missing data: missing = smoking, last observation carried forward, and a little multiple imputation. AB - AIMS: Analysis of binary outcomes with missing data is a challenging problem in substance abuse studies. We consider this problem in a simple two-group design where interest centers on comparing the groups in terms of the binary outcome at a single timepoint. DESIGN: We describe how the deterministic assumptions of missing = smoking and last observation carried forward (LOCF) can be relaxed by allowing missingness to be related imperfectly to the binary outcome, either stratified on past values of the outcome or not. We also describe use of multiple imputation to take into account the uncertainty inherent in the imputed data. SETTING: Data were analyzed from a published smoking cessation study evaluating the effectiveness of adding group-based treatment adjuncts to an intervention comprised of a television program and self-help materials. PARTICIPANTS: Participants were 489 smokers who registered for the television-based program and who indicated an interest in attending group-based meetings. MEASUREMENTS: The measurement of the smoking outcome was conducted via telephone interviews at post intervention and at 24 months. FINDINGS AND CONCLUSIONS: The significance of the group effect did vary as a function of the assumed relationship between missingness and smoking. The 'conservative' missing = smoking assumption suggested a beneficial group effect on smoking cessation, which was confirmed via a sensitivity analysis only if an extreme odds ratio of 5 between missingness and smoking was assumed. This type of sensitivity analysis is crucial in determining the role that missing data play in arriving at a study's conclusions. PMID- 17854334 TI - Alcohol consumption and cardiovascular mortality accounting for possible misclassification of intake: 11-year follow-up of the Melbourne Collaborative Cohort Study. AB - AIMS: To investigate the relationship between usual daily alcohol intake, beverage type and drinking frequency on cardiovascular (CVD) and coronary heart disease (CHD) mortality, accounting for systematic misclassification of intake. DESIGN: Prospective cohort study with mean follow-up of 11.4 years. Setting The Melbourne Collaborative Cohort Study, Australia. PARTICIPANTS: A total of 38 200 volunteers (23 044 women) aged 40-69 years at baseline (1990-1994). MEASUREMENTS: Self-reported alcohol intake using beverage-specific quantity-frequency questions (usual intake) and drinking diary for previous week. FINDINGS: Compared with life time abstention, usual daily alcohol intake was associated with lower CVD and CHD mortality risk for women but not men. For women, the hazard ratio [HR (95% CI)] for CVD for those drinking > 20 g/day alcohol was 0.43 (0.19-0.95; P trend = 0.18), and for CHD, 0.19 (0.05-0.82; P trend = 0.24). Male former drinkers had over twice the mortality risk for CVD [HR = 2.58 (1.51-4.41)] and CHD [HR = 2.91 (1.59-5.33)]. Wine was the only beverage associated inversely with mortality for women. Compared with drinkers who consumed no alcohol in the week before baseline, drinking frequency was associated inversely with CVD and CHD mortality risk for men but not women. HR for men drinking 6-7 days/week was 0.49 (0.29 0.81; P trend = 0.02) for CVD, and 0.49 (0.26-0.92: P trend = 0.23) for CHD. CONCLUSIONS: Usual daily alcohol intake was associated with reduced CVD and CHD mortality for women but not men. This benefit appeared to be mainly from wine, although comparison of beverages was not possible. Drinking frequency was associated inversely with CVD and CHD death for men but not women. PMID- 17854335 TI - Do the protective effects fade away? PMID- 17854336 TI - Effects of home access and availability of alcohol on young adolescents' alcohol use. AB - AIMS: The purpose of the present study was to examine the effects of parental provision of alcohol and home alcohol accessibility on the trajectories of young adolescent alcohol use and intentions. DESIGN: Data were part of a longitudinal study of alcohol use among multi-ethnic urban young adolescents who were assigned randomly to the control group of a prevention trial. SETTING: Data were collected from a cohort of youth, and their parents, who attended public schools in Chicago, Illinois (2002-2005). PARTICIPANTS: The sample comprised the 1388 students, and their parents, who had been assigned randomly to the control group and were present and completed surveys at baseline, in the beginning of 6th grade (age 12). The sample was primarily low-income, and African American and Hispanic. MEASUREMENTS: Students completed self-report questionnaires when in the 6th, 7th and 8th grades (age 12-14 years; response rates 91-96%). Parents of the 6th grade students also completed questionnaires (70% response rate). FINDINGS: Student report, at age 12, of parental provision of alcohol and home alcohol availability, and parental report of providing alcohol to their child and the accessibility of alcohol in the home, were associated with significant increases in the trajectories of young adolescent alcohol use and intentions from ages 12 14 years. Student report of receiving alcohol from their parent or taking it from home during their last drinking occasion were the most robust predictors of increases in alcohol use and intentions over time. CONCLUSIONS: Results indicate that it is risky for parents to allow children to drink during early adolescence. When these findings are considered together with the risks associated with early onset of alcohol use, it is clear that parents can play an important role in prevention. PMID- 17854337 TI - The impact of later trading hours for hotels (public houses) on breath alcohol levels of apprehended impaired drivers. AB - AIM: To examine the impact of extended trading permits (ETPs) for licensed hotels in Perth, Western Australia on impaired driver breath alcohol levels (BALs) between July 1993 and June 1997. DESIGN: Forty-three hotels obtained ETPs allowing later closing hours and 130 maintained standard closing time (controls). Impaired driver BALs were linked to 'last place of drinking' hotels. Before and after period BALs of drivers who last drank at ETP or non-ETP hotels were compared by time of day of apprehension and sex, controlling for age. FINDINGS: Impaired female drivers apprehended between 10.01 p.m. and 12 midnight (before closing time) had significantly lower BALs after drinking at ETP hotels. Male drivers aged 18-25 years and apprehended between 12.01 and 2.00 a.m. after drinking at ETP hotels had significantly higher BALs than drivers who drank at non-ETP hotels. CONCLUSIONS: At peak times for alcohol-related offences, late trading is associated with higher BALs among those drinkers most at risk of alcohol-related harm. PMID- 17854338 TI - Randomized sanctions to reduce re-offense among repeat impaired-driving offenders. AB - AIMS: This study, conducted within a driving under the influence (DUI) court intervention, evaluated the degree to which removing electronic monitoring (EM) and/or mandatory vehicle sales requirements increased rates of post-sentence traffic violations among repeat DUI offenders. DESIGN: Randomized trial. SETTING AND PARTICIPANTS: A total of 477 repeat DUI offenders entering the Driving under the Influence of Intoxicants (DUII) Intensive Supervision Program (DISP), Multnomah County, Oregon. INTERVENTION: Subjects were randomized into four intervention groups. Group 1: standard DISP with EM and vehicle sales requirements; group 2: standard DISP with mandatory vehicle sale, but without EM; group 3: standard DISP with EM, but without mandatory vehicle sale; and group 4: standard DISP without EM or mandated vehicle sale. Standard DISP includes treatment for alcohol abuse and dependence, polygraph testing, regular court appearances, and probation or court-based monitoring. MEASUREMENTS: The risk of re-arrest for traffic violations was compared among the four groups using hazard ratio estimates from complementary log-log regression models. FINDINGS: Compared with group 1, subjects in group 2 initially had increased re-arrest risks, but this effect dissipated within 3 years of entering DISP. Group 3 subjects had a 96% increase in re-arrest rates. Group 4 subjects had smaller increased risks than predicted, with re-arrest rates similar to those of group 1 at the end of the follow-up period. CONCLUSIONS: Although some of the findings suggest that mandatory vehicle sales may deter future traffic violations, inconsistent results across groups make this finding equivocal. Positive effects of EM, while large in the short term, appear to have a relatively small long-term value in reducing traffic arrest rates. PMID- 17854339 TI - Determinants of injection drug user (IDU) syringe sharing: the relationship between availability of syringes and risk network member characteristics in Winnipeg, Canada. AB - AIMS: Despite the establishment of syringe exchange programmes, syringe-sharing behaviour remains common among some injection drug users (IDU). Previous studies have identified several individual- and social network-level variables associated with syringe sharing. We examine the extent to which each of these variables is related independently to this behaviour within a diverse study population. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional survey of 435 IDU conducted between December 2003 and September 2004 in Winnipeg, Canada. MEASUREMENTS: Individual and social-network variables were obtained from a survey instrument administered through a personal interview. Syringe sharing was defined as receptive syringe sharing in the last 6 months. Logistic regression analysis with generalized estimating equations was used to determine simultaneously the role of individual-level and risk network member-level variables on the odds of syringe sharing. FINDINGS: Individuals' relationship to a risk network member (sex partner, OR: 15.3 95% CI: 7.6-30.8; family member, OR: 3.4 95% CI: 1.3-9.0) and difficulty of access to syringes (OR: 3.6 95% CI: 1.3-9.9) were predictive of syringe sharing. Dyads who 'often' pooled resources to obtain drugs were at 4.9 times (95% CI: 2.1-11.6) the odds of syringe sharing, while those who 'sometimes' pooled resources were at 2.8 times (95% CI: 1.1-6.7) the odds, compared to those who 'never' pooled resources together. CONCLUSIONS: Syringe sharing in this population depended on both the availability of clean syringes and social network relationships. Adopting interventions that take into account relationships and behaviours that shape social norms present in networks/dyads would be a necessary prevention strategy alongside the provision of clean syringes. PMID- 17854340 TI - Reducing syringe sharing among injecting drug users in Winnipeg: 81% success or 19% failure? PMID- 17854341 TI - Evaluation of a transdermal buprenorphine formulation in opioid detoxification. AB - AIMS: Buprenorphine is marketed in a sublingual formulation for treatment of opioid dependence. A transdermal formulation has been developed that may provide extended relief from opioid withdrawal, reduce required clinic visits and improve adherence, while having less potential for diversion and abuse. This study evaluated the safety and biodelivery (blood levels) of this transdermal buprenorphine formulation (i.e. buprenorphine patch), and its apparent efficacy in suppressing the opioid withdrawal syndrome. DESIGN: Open-label, first-in humans trial. SETTING: A residential research facility. PARTICIPANTS: Nine physically dependent opioid-users completed the 10-day opioid detoxification study. INTERVENTION: Each volunteer received a single patch application that remained in place for 3 days. The formulation has shown an average delivery of 1.9 mg/day of buprenorphine over 3 days in pre-clinical evaluation. MEASURES: Physiological, behavioral, subjective and observer ratings of opioid withdrawal and opioid agonist effects were collected. FINDINGS: Overall, the patch appeared safe and well tolerated. There were no serious adverse events, and no opioid intoxication following patch application. Oxygen saturation, heart rate, blood pressure, skin temperature and pupil diameter remained well within normal ranges. Buprenorphine blood levels peaked 48 hours after patch application at a concentration of 0.60 ng/ml. Volunteers' self-reports of the presence and severity of withdrawal symptoms were reduced by approximately 50% on the 3 days of patch application. Withdrawal symptoms increased marginally upon patch removal. Administration of opioid rescue medication was eliminated within 6 hours of patch application, and increased slightly upon patch removal. CONCLUSIONS: The significant biodelivery of buprenorphine and the suppression of the opioid withdrawal syndrome during patch application and its reappearance after patch removal indicate clinically useful pharmacodynamic activity. Transdermal buprenorphine may be a useful opioid detoxification treatment that reduces compliance concerns, and delivers buprenorphine in a formulation less likely to be diverted to illicit use. PMID- 17854342 TI - Is attributing smoking to genetic causes associated with a reduced probability of quit attempt success? A cohort study. AB - AIMS: Pharmacogenetic smoking cessation interventions would involve smokers being given information about the influence of genes on their behaviour. However, attributing smoking to genetic causes may reduce perceived control over smoking, reducing quit attempt success. This study examines whether attributing smoking to genetic influences is associated with reduced quitting and whether this effect is mediated by perceived control over smoking. DESIGN: Cohort study. PARTICIPANTS: A total of 792 smokers, participating in a trial of nicotine replacement therapy (NRT)-assisted smoking cessation. Participants were informed that the trial investigated relationships between genetic markers and smoking behaviour, but personalized genetic feedback was not provided. SETTING: Primary care in Oxfordshire and Buckinghamshire, UK. MEASUREMENTS: Perceived control over smoking and perceived importance of genetic factors in causing smoking assessed pre-quit; abstinence 4, 12, 26 and 52 weeks after the start of treatment. FINDINGS: A total of 515 smokers (65.0%) viewed genetic factors as playing some role in causing their smoking. They had lower perceived control over smoking than smokers who viewed genetic factors as having no role in causing their smoking. Attributing smoking to genetic causes was not associated significantly with a lower probability of quit attempt success. CONCLUSIONS: Attributing smoking to genetic factors was associated with lower levels of perceived control over smoking but not lower quit rates. This suggests that learning of one's genetic predisposition to smoking during a pharmacogenetically tailored smoking cessation intervention may not deter quitting. Further research should examine whether the lack of impact of genetic attributions on quit attempt success is also found in smokers provided with personalized genetic feedback. PMID- 17854343 TI - The role of schoolmates' smoking and non-smoking in adolescents' smoking transitions: a longitudinal study. AB - AIMS: The first longitudinal investigation of the extent to which same-age and older schoolmates' smoking and non-smoking are associated with adolescents' smoking transitions during three grade intervals. DESIGN: Same-age and older schoolmates' smoking and non-smoking were assessed when adolescents were at grades 5 (age 10), 7 (age 12) and 9 (age 14). Adolescents' smoking transitions were assessed at three grade intervals: 5th-7th (age 10-12), 7th-9th (age 12-14) and 9th-12th (age 14-17). SETTING: Forty Washington State school districts. PARTICIPANTS AND MEASUREMENTS: Smoking questionnaire data were gathered on a cohort of adolescents (n = 4354 for same-age schoolmate analysis; n = 1833 for older schoolmate analysis) that was 49% female and 91% Caucasian. FINDINGS: No significant evidence that same-age schoolmates' smoking or non-smoking was associated with any of the adolescent smoking transitions at any of the three grade intervals. In contrast, the probability that each older schoolmate's smoking was associated with the adolescent making the transition to trying smoking was 1% (95% CI: 0.4%, 1.5%) and with the transition from trying to monthly smoking was also 1% (95% CI: 0.2%, 2.0%) during the 7th-9th grade (age 12 14) interval. Moreover, each older schoolmate's non-smoking was associated with a 1.001-1.006 (all P < 0.05) relative risk of an adolescent not trying smoking or escalating from trying to monthly smoking at several grade intervals. CONCLUSIONS: Interventions should perhaps focus on the influence of both smoking and non-smoking older schoolmates during late childhood and early adolescence. PMID- 17854344 TI - Classic texts revisited. PMID- 17854346 TI - Human embryonic stem cell-derived neural precursors as a continuous, stable, and on-demand source for human dopamine neurons. AB - Human embryonic stem (hES) cells can be guided to differentiate into ventral midbrain-type neural precursor (NP) cells that proliferate in vitro by specific mitogens. We investigated the potential of these NP cells derived from hES cells (hES-NP) for the large-scale generation of human dopamine (DA) neurons for functional analyses and therapeutic applications. To address this, hES-NP cells were expanded in vitro for 1.5 months with six passages, and their proliferation and differentiation properties determined over the NP passages. Interestingly, the total hES-NP cell number was increased by > 2 x 10(4)-folds over the in vitro period without alteration of phenotypic gene expression. They also sustained their differentiation capacity toward neuronal cells, exhibiting in vitro pre synaptic DA neuronal functionality. Furthermore, the hES-NP cells can be cryopreserved without losing their proliferative and developmental potential. Upon transplantation into a Parkinson's disease rat model, the multi-passaged hES NP cells survived, integrated into the host striatum, and differentiated toward the neuronal cells expressing DA phenotypes. A significant reduction in the amphetamine-induced rotation score of Parkinson's disease rats was observed by the cell transplantation. Taken together, these findings indicate that hES-NP cell expansion is exploitable for a large-scale generation of experimental and transplantable DA neurons of human-origin. PMID- 17854347 TI - Uncoupling is without an effect on the production of reactive oxygen species by in situ synaptic mitochondria. AB - Earlier reports that generation of reactive oxygen species (ROS) by isolated mitochondria supported by succinate was sensitive to small changes in the mitochondrial membrane potential (DeltaPsim) served as a basis for the concept of 'mild uncoupling' suggesting that a few millivolts decrease in DeltaPsim would be beneficial in neuroprotection because of reducing the production of ROS by mitochondria. In this study, we tested whether ROS generation by in situ mitochondria, which function in a normal cytosolic environment and oxidize glucose-derived physiological substrates, is also dependent on changes in DeltaPsim. The release of H(2)O(2) was measured by the Amplex red fluorescence assay in freshly prepared isolated nerve terminals, synaptosomes incubated in a glucose-containing medium. DeltaPsim was decreased by the uncoupler carbonyl cyanide-p-trifluoromethoxyphenyl-hydrazon (FCCP) (10-200 nmol/L), which accelerated the oxygen consumption, decreased the NADH level and induced depolarization, as shown by the fluorescence indicator JC-1, in in situ mitochondria. These changes were detected at already the smallest FCCP concentration. H(2)O(2) generation, however, was found to be unaltered by FCCP at any of the applied concentration. Depolarization of mitochondria was also induced by veratridine (40 mumol/L), which enhances the cytosolic Na(+) concentration and imposes an ATP demand in synaptosomes. The accelerated oxygen consumption and the small depolarization of in situ mitochondria by veratridine were not paralleled by any significant alteration in the ROS generation. These findings indicate that a basal ROS generation by in situ mitochondria is not sensitive to changes in DeltaPsim challenging the rational of the 'mild uncoupling' theory for neuroprotection and suggest that the DeltaPsim-dependent characteristics of ROS generation is limited mainly to well-coupled succinate-supported isolated mitochondria. PMID- 17854348 TI - Reorganization of prion protein membrane environment during low potassium-induced apoptosis in primary rat cerebellar neurons. AB - We studied the changes occurring in the membrane environment of prion protein (PrP) during apoptosis induced by low potassium in primary rat cerebellar neurons. Ceramide levels increased during apoptosis-inducing treatment, being doubled with respect to time-matched controls after 24 h. Sphingomyelin levels were parallely decreased, while cholesterol and ganglioside contents were not affected. Changes in ceramide and sphingomyelin composition were exclusively restricted to a detergent-resistant membrane fraction. The pro-apoptotic treatment was accompanied by the down-regulation of PrP and of the non-receptor kinase Fyn. The levels of PrP and Fyn were correspondingly reduced in the detergent-resistant membrane fraction. In control cells, the membrane microenvironment separated by immunoprecipitation with anti-PrP antibody contained 80% of the detergent-resistant PrP and 35% and 38% of the sphingolipids and cholesterol respectively. Upon low potassium treatment, 20% of the PrP originally present in the detergent-resistant fraction was immunoprecipitated, together with 19% of sphingolipids and 22% of cholesterol. Thus, PrP in the immunoprecipitate from apoptotic cells was ninefold less than in control ones, while sphingolipids and cholesterol were about 50% with respect to controls cells. The molar ratio between cholesterol, sphingomyelin and ceramide was 15 : 6 : 1 in the PrP-rich environment from control neurons, and 6 : 2 : 1 in that from apoptotic cells. PMID- 17854349 TI - Neuroprotective actions of noradrenaline: effects on glutathione synthesis and activation of peroxisome proliferator activated receptor delta. AB - The endogenous neurotransmitter noradrenaline (NA) can protect neurons from the toxic consequences of various inflammatory stimuli, however the exact mechanisms of neuroprotection are not well known. In the current study, we examined neuroprotective effects of NA in primary cultures of rat cortical neurons. Exposure to oligomeric amyloid beta (Abeta) 1-42 peptide induced neuronal damage revealed by increased staining with fluorojade, and toxicity assessed by LDH release. Abeta-dependent neuronal death did not involve neuronal expression of the inducible nitric oxide synthase 2 (NOS2), since Abeta did not induce nitrite production from neurons, LDH release was not reduced by co-incubation with NOS2 inhibitors, and neurotoxicity was similar in wildtype and NOS2 deficient neurons. Co-incubation with NA partially reduced Abeta-induced neuronal LDH release, and completely abrogated the increase in fluorojade staining. Treatment of neurons with NA increased expression of gamma-glutamylcysteine ligase, reduced levels of GSH peroxidase, and increased neuronal GSH levels. The neuroprotective effects of NA were partially blocked by co-treatment with an antagonist of peroxisome proliferator activated receptors (PPARs), and replicated by incubation with a selective PPARdelta (PPARdelta) agonist. NA also increased expression and activation of PPARdelta. Together these data demonstrate that NA can protect neurons from Abeta-induced damage, and suggest that its actions may involve activation of PPARdelta and increases in GSH production. PMID- 17854351 TI - Protection of dopaminergic neurons by electroconvulsive shock in an animal model of Parkinson's disease. AB - Electroconvulsive shock (ECS) improves motor function in Parkinson's disease. In rats, ECS stimulates the expression of various factors some of which have been proposed to exert neuroprotective actions. We have investigated the effects of ECS on 6-hydroxydopamine (6-OHDA)-injected rats. Three weeks after a unilateral administration of 6-OHDA, 85-95% nigral dopaminergic neurons are lost. Chronic ECS prevented this cell loss, protect the nigrostriatal pathway (assessed by FloroGold retrograde labeling) and reduce motor impairment in 6-OHDA-treated animals. Injection of 6-OHDA caused loss of expression of glial cell-line derived neurotrophic factor (GDNF) in the substantia nigra. Chronic ECS completely prevented this loss of GDNF expression in 6-OHDA-treated animals. We also found that protected dopaminergic neurons co-express GDNF receptor proteins. These results strongly suggest that endogenous changes in GDNF expression may participate in the neuroprotective mechanism of ECS against 6-OHDA induced toxicity. PMID- 17854350 TI - Post-synaptic density perturbs insulin-induced Kv1.3 channel modulation via a clustering mechanism involving the SH3 domain. AB - The olfactory bulb (OB) contains the highest concentration of the insulin receptor (IR) kinase in the central nervous system; however, its functional role and modulation in this region remains poorly understood. IR kinase contains a number of proline-rich motifs, making it an excellent candidate for modulation by SH(3) domain-containing adaptor proteins. Kv1.3, a voltage-gated Shaker potassium channel and tyrosine phosphorylation substrate of IR kinase, contains several proline-rich sequences and a canonical post-synaptic density 95 (PSD-95)/discs large/zO-1 domain (PDZ) recognition motif common to most Shaker family members. We sought to determine if a functional relationship existed between Kv1.3, IR kinase, and the SH(3)/PDZ adaptor protein PSD-95. Through patch-clamp electrophysiology, immunochemistry, and co-immunoprecipitation, we found that while Kv1.3 and PSD-95 alone interact via the canonical C-terminal PDZ recognition motif of the channel, this molecular site of interaction acts to cluster the channels but the PSD-95 SH(3)-guanylate kinase domain functionally modulates Kv1.3 activity via two proline-rich domains in its N- and C-terminal. Therefore, these data suggest that adaptor domains responsible for ion-channel clustering and functional modulation are not necessarily coupled. Moreover, IR kinase and Kv1.3 can only be co-immunoprecipitated in the presence of PSD-95 as the adapting linker. Functionally, insulin-dependent Kv1.3 phosphorylation that causes channel current suppression is blocked via interaction with the PSD-95 SH(3)-guanylate kinase domain. Because all the three proteins co-localize in multiple lamina of the OB that are known to be rich in synaptic connections, membrane excitability and synaptic transmission at critical locations in the OB have the capacity to be finely regulated. PMID- 17854352 TI - Role of IFN-gamma in an experimental murine model of West Nile virus-induced seizures. AB - Seizures are a major complication of viral encephalitis. However, the mechanisms of seizure-associated neuronal dysfunction remain poorly understood. We report that intranasal inoculation with West Nile virus (WNV) (Sarafend) causes limbic seizures in C57BL/6 mice, but not in interferon (IFN)-gamma-deficient (IFN-gamma /-) mice. Both strains showed similar levels of virus in the brain, as well as similar concentrations of the cytokines, tumor necrosis factor and interleukin-6, both of which can alter neuronal excitability. Experiments in chimeric IFN-gamma /- mice reconstituted with IFN-gamma-producing leukocytes showed that IFN-gamma is not required during central nervous system infection for limbic seizure development, suggesting a role for IFN-gamma in the developing brain. This was supported responses to pentylenetetrazole, kainic acid (KA), and N-methyl-d aspartate (NMDA). Both strains of mice exhibited similar behavior after pentylenetetrazole challenge. However, while NMDA and KA treatment resulted in characteristic seizures in C57BL/6 mice, these responses were diminished (NMDA treatment) or absent (KA treatment) in IFN-gamma-/- mice. Furthermore, NMDA receptor blockade with MK-801 in WNV-infected C57BL/6 mice abrogated seizures and prolonged survival. Our data show that IFN-gamma plays an important role in the development of the excitatory seizure pathways in the brain and that these cascades become pathogenic in encephalitic WNV infection. PMID- 17854353 TI - The safety of tacrolimus ointment for the treatment of atopic dermatitis: a review. AB - Tacrolimus ointment is a topical calcineurin inhibitor (TCI) that was developed specifically for the treatment of atopic dermatitis (AD). It is one of the most extensively tested dermatological products, with more than 19 000 patients (including approximately 7600 children) having participated in the tacrolimus ointment clinical development programme. Recent regulatory reviews have focused on the potential risk of malignancy with TCIs, based on their mode of action and the effects of systemic tacrolimus when given to transplant recipients. Studies have shown, however, that the systemic absorption of tacrolimus when applied topically is very low, with blood concentrations being below the level of quantification in most patients. Moreover, TCIs are not associated with a decrease in immunocompetence in the skin and there is no increase in the incidence of infections with long-term treatment. More than 5.4 million prescriptions for tacrolimus ointment have been issued worldwide, with no evidence of an increased risk of malignancy in adults or children compared with the general population. Similarly, epidemiological studies have failed to demonstrate an increased incidence of skin cancer in patients using TCIs. The most common adverse events (AEs) that occur with tacrolimus ointment treatment are transient application-site reactions, such as burning or pruritus. These complications are related to disease severity, and decrease in frequency over time as AD improves. The incidence of nonapplication-site AEs does not increase with long-term treatment, and most such events occurring in clinical trials were considered to be unrelated to therapy. Although it is important that clinicians are aware of the recent changes in product labelling, extensive clinical trials continue to show that tacrolimus ointment is well tolerated, and is generally an effective therapy for suitable patients with AD. PMID- 17854354 TI - Steroid allergy in patients with inflammatory bowel disease. AB - BACKGROUND: Contact allergy to a steroid enema leading to worsening of inflammatory bowel disease (IBD) has recently been reported. This study was designed to look for evidence of steroid allergy in patients with IBD. OBJECTIVES: To look for the presence of steroid allergy in general, and steroid enema allergy in particular, in a cohort of IBD patients prepared to attend for patch testing. METHODS: Patients with IBD in two gastroenterology units at Dublin and Cork were asked to take part in the study. Those who agreed to take part were tested to the British Contact Dermatitis Society standard and steroid batteries. Patients with positive tests to steroids were subsequently asked to attend for intradermal testing with prednisolone, and patch testing to the two commercially available steroid enemas in Ireland and an extended battery of steroids. Reactions were read at days 2 and 4. RESULTS: In total, 44 patients from the two units were patch tested. Four patients had positive patch tests to one or more steroids in these batteries: budesonide (n = 2), triamcinolone acetonide (n = 1), tixocortol pivalate (n = 1) and prednisolone (n = 1). Of these, three underwent further testing. All three had positive reactions to intradermal prednisolone and one had a positive test to steroid enema. CONCLUSIONS: Four (9%) of our patients were found to have steroid allergy. This has important implications for the local and systemic treatment of their IBD. PMID- 17854355 TI - Concordant lymphoma of cutaneous anaplastic large cell lymphoma and systemic B cell leukaemia. PMID- 17854356 TI - Radiation recall dermatitis in a patient affected with pheochromocytoma after treatment with lanreotide. PMID- 17854357 TI - Infliximab-induced acne: report of a third case. PMID- 17854358 TI - Disseminated cryptococcal infection in a patient with severe psoriasis treated with efalizumab, methotrexate and ciclosporin. PMID- 17854359 TI - PTPN22 R620W polymorphism is not associated with pemphigus. PMID- 17854360 TI - Arndt-Gottron scleromyxoedema: successful therapy with intravenous immunoglobulins. PMID- 17854361 TI - Can automated dermoscopy image analysis instruments provide added benefit for the dermatologist? A study comparing the results of three systems. AB - BACKGROUND: Instruments designed to provide computer program-driven diagnosis of dermoscopic images of lesions are now commercially available. Multiple publications tout the improved diagnostic accuracy of these instruments compared with that of clinicians. OBJECTIVES: Our aim was to evaluate the actual usefulness of these instruments for dermatologists practising in a pigmented lesion clinic. METHODS: Over a 4-month period we subjected lesions, which were being evaluated in one of our clinics, to automated computer diagnosis performed by three commercially available instruments. We intentionally included three groups of lesions: group 1 lesions were suspicious melanocytic lesions that were scheduled to be excised; group 2 lesions were nonmelanocytic lesions; group 3 lesions were clinically obvious melanomas. The automated diagnoses provided by the instruments were compared with the dermoscopy diagnosis of experienced physicians and with histopathology. RESULTS: We included a total of 107 lesions. One imaging system's computer algorithm was unable to analyse one third of the lesions. All three instruments' computer algorithms were able to identify the clinically obvious melanomas (group 3) correctly. However, all three systems tended to overdiagnose by incorrectly classifying most seborrhoeic keratoses (group 2) as potential malignant lesions. Concerning the suspect melanocytic lesions (group 1), which are precisely the lesions for which a dermatologist would welcome a second opinion, we found significant variability in the diagnostic accuracy of the instruments tested. However, all three systems providing computer-assisted diagnosis had a tendency to overdiagnose benign melanocytic lesions as potential melanomas. CONCLUSIONS: Although the image analysis systems tested by us correctly identified the clinically obvious melanomas, they were not able to discriminate between most dysplastic naevi and early malignant melanoma. Thus, for the moment these computer-assisted diagnostic imaging machines provide little to no added benefit for the experienced dermatologist/dermoscopist. PMID- 17854362 TI - Association of human herpesvirus 6 reactivation with the flaring and severity of drug-induced hypersensitivity syndrome. AB - BACKGROUND: Drug-induced hypersensitivity syndrome (DIHS) is an adverse reaction with clinical signs of fever, rash and internal organ involvement. In the vast majority of patients in Japan, the causative drugs for DIHS are limited to the following eight: carbamazepine, phenytoin, phenobarbital, zonisamide, mexiletine, dapsone, salazosulfapyridine and allopurinol. The association of human herpesvirus (HHV)-6 reactivation with DIHS has been reported by various groups. OBJECTIVES: To confirm the relationship between the flaring and severity of DIHS and HHV-6 reactivation. METHODS: We evaluated 100 patients with drug rash and systemic symptom(s) caused by the drugs associated with DIHS. HHV-6 reactivation was examined by serological antibody assay and quantitative real-time polymerase chain reaction assay of serial serum samples. RESULTS: Anti-HHV-6 IgG titres increased in 62 of 100 patients, 14-28 days after the onset of symptoms. These patients suffered from severe organ involvement and a prolonged course compared with 38 patients showing no reactivation of HHV-6. Significant amounts of HHV-6 DNA were detected in serum samples from 18 of the 62 patients. Flaring of symptoms such as fever and hepatitis was closely related to HHV-6 reactivation in these 18 patients. It should be emphasized that all five patients with fatal outcome and 10 patients with renal failure were in the HHV-6 reactivation group. CONCLUSIONS: A combination of immunological reaction to a drug and HHV-6 reactivation results in the severe course of DIHS. The demonstration of HHV-6 reactivation is a useful marker of diagnosis as well as prognosis in DIHS. PMID- 17854363 TI - Matrix metalloproteinases as mediators of tissue injury in different forms of cutaneous lupus erythematosus. AB - BACKGROUND: Matrix metalloproteinases (MMPs) contribute to tissue destruction, regeneration, inflammation and apoptosis and several of them are upregulated by ultraviolet (UV) radiation in skin. Although some MMPs associate with organ manifestations of systemic lupus erythematosus (SLE), their role in cutaneous lupus erythematosus (LE) is elusive. OBJECTIVES: Our aim was to evaluate the expression of MMPs in SLE, subacute cutaneous LE (SCLE) and discoid LE (DLE) skin lesions and their relation to apoptosis and epidermal changes. METHODS: Lesional skin biopsies from 20 patients with SLE, 20 with DLE and 17 with SCLE, and from UVA/UVB-photoprovoked skin of healthy volunteers were immunostained using antibodies to multiple MMPs and tissue inhibitors of metalloproteinases (TIMPs). The TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling) method was used for detection of apoptosis. RESULTS: MMP-3, -10, -19 and -26 were abundantly expressed by keratinocytes in SLE, DLE and SCLE skin samples. MMP-7 was detected in keratinocytes in regions of oedema and vacuolization especially in SLE and SCLE, while MMP-14 was only occasionally observed in keratinocytes. Photoprovocation did not induce MMP-10 or -26 expression in skin of healthy volunteers. Epithelial TIMP-1 expression was low while occasional positive fibroblasts were seen in the dermis. TIMP-3 was abundantly expressed in the epidermis, endothelial cells and macrophages. CONCLUSIONS: Different subtypes of cutaneous LE are fairly similar in their MMP expression profile. MMP-3 and -10 mediate both epidermal changes and dermal tissue remodelling but are not present in lymphocytes. Low expression of TIMP-1 suggests that lupus skin is characterized by proteolytic events, and targeted action using selective MMP inhibitors may reduce lupus-induced damage in inflamed tissues. PMID- 17854364 TI - CD8+ poikilodermatous mycosis fungoides with a nonaggressive clinical behaviour and a good response to psoralen plus ultraviolet A treatment. PMID- 17854365 TI - Post-kala-azar dermal leishmaniasis as an immune reconstitution inflammatory syndrome in a patient with acquired immune deficiency syndrome. AB - Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL) observed mainly in Sudan and India where it follows treated VL in 50% and 10% of cases, respectively. We report a 46-year-old patient with acquired immune deficiency syndrome who, 7 months after diagnosis of VL, developed PKDL and uveal leishmaniasis following HAART-induced immune recovery. In southern Europe PKDL seems to be an emerging clinical presentation among human immunodeficiency virus (HIV)-infected patients experiencing HAART-induced immune recovery after a previous diagnosis of VL. The best treatment among HIV-infected patients remains to be determined. PMID- 17854366 TI - Risk factors for acute generalized exanthematous pustulosis (AGEP)-results of a multinational case-control study (EuroSCAR). AB - BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a disease characterized by the rapid occurrence of many sterile, nonfollicular pustules usually arising on an oedematous erythema often accompanied by leucocytosis and fever. It is usually attributed to drugs. OBJECTIVES: To evaluate the risk for different drugs of causing AGEP. PATIENTS AND METHODS: A multinational case control study (EuroSCAR) conducted to evaluate the risk for different drugs of causing severe cutaneous adverse reactions; the study included 97 validated community cases of AGEP and 1009 controls. Results Strongly associated drugs, i.e. drugs with a lower bound of the 95% confidence interval (CI) of the odds ratio (OR) > 5 were pristinamycin (CI 26-infinity), ampicillin/amoxicillin (CI 10 infinity), quinolones (CI 8.5-infinity), (hydroxy)chloroquine (CI 8-infinity), anti-infective sulphonamides (CI 7.1-infinity), terbinafine (CI 7.1-infinity) and diltiazem (CI 5.0-infinity). No significant risk was found for infections and a personal or family history of psoriasis (CI 0.7-2.2). CONCLUSIONS: Medications associated with AGEP differ from those associated with Stevens-Johnson syndrome or toxic epidermal necrolysis. Different timing patterns from drug intake to reaction onset were observed for different drugs. Infections, although possible triggers, played no prominent role in causing AGEP and there was no evidence that AGEP is a variant of pustular psoriasis. PMID- 17854367 TI - Differentiation of tumour-stage mycosis fungoides, psoriasis vulgaris and normal controls in a pilot study using serum proteomic analysis. AB - BACKGROUND: Serum proteomic analysis is an analytical technique utilizing high throughput mass spectrometry (MS) in order to assay thousands of serum proteins simultaneously. The resultant 'proteomic signature' has been used to differentiate benign and malignant diseases, enable disease prognosis, and monitor response to therapy. OBJECTIVES: This pilot study was designed to determine if serum protein patterns could be used to distinguish patients with tumour-stage mycosis fungoides (MF) from patients with a benign inflammatory skin condition (psoriasis) and/or subjects with healthy skin. METHODS: Serum was analysed from 45 patients with tumour-stage MF, 56 patients with psoriasis, and 47 controls using two MS platforms of differing resolution. An artificial intelligence-based classification model was constructed to predict the presence of the disease state based on the serum proteomic signature. RESULTS: Based on data from an independent testing set (14-16 subjects in each group), MF was distinguished from psoriasis with 78.6% (or 78.6%) sensitivity and 86.7% (or 93.8%) specificity, while sera from patients with psoriasis were distinguished from those of nonaffected controls with 86.7% (or 93.8%) sensitivity and 75.0% (or 76.9%) specificity (depending on the MS platform used). MF was distinguished from unaffected controls with 61.5% (or 71.4%) sensitivity and 91.7% (or 92.9%) specificity. In addition, a secondary survival analysis using 11 MS peaks identified significant survival differences between two MF groups (all P-values <0.05). CONCLUSIONS: Serum proteomics should be further investigated for its potential to identify patients with neoplastic skin disease and its ability to determine disease prognosis. PMID- 17854368 TI - Acrodermatitis continua of Hallopeau due to oral terbinafine. PMID- 17854369 TI - The 'handprint' approximates to 1% of the total body surface area whereas the 'palm minus the fingers' does not. PMID- 17854370 TI - The rapid onset of multiple squamous cell carcinomas during etanercept treatment for psoriasis. PMID- 17854371 TI - Topical imiquimod in the treatment of a long-standing capillary malformation. PMID- 17854372 TI - A case of do-it-yourself Mohs' surgery using bloodroot obtained from the internet. PMID- 17854373 TI - Male genital lichen sclerosus and tacrolimus. PMID- 17854374 TI - Resistance to hydroxychloroquine due to smoking in a patient with lupus erythematosus tumidus. PMID- 17854375 TI - Pityriasis lichenoides: the differences between children and adults. AB - BACKGROUND: Pityriasis lichenoides (PL) is a skin disease that affects both children and adults. Anecdotally, it is said to run a more benign course in children, with a frequent tendency to self-resolution. However, to our knowledge, there have been no published studies comparing PL in both age groups. OBJECTIVE: To evaluate the clinicopathological features, overall efficacy of treatments and disease outcomes in children and adults diagnosed with PL. METHODS: A retrospective review of records was undertaken on all patients diagnosed with PL at two regional centres during an 8-year period (from 1998 to 2006). For each individual, data were collected on age, sex, number of lesions, lesional morphology and distribution, symptoms, histopathological features, treatment modalities (and response), overall follow-up and length of remission. RESULTS: We recorded 25 children (median age 8 years, range 2-18) and 32 adults (median age 40 years, range 20-65) with PL. All the children and adults had more than 20 scaly, papular lesions. Children had greater lesional body involvement than adults. Lesions on the legs and trunk were present in 23 children (92%) compared with 19 adults (59%) (P < 0.01) and facial involvement was observed more commonly in children (n = 10, 40%) compared with adults (n = 8, 25%). Dyspigmentation was significantly more common in children (n = 18, 72%) compared with adults (n = 6, 19%) (P < 0.001). Topical corticosteroids were used by 16 children (64%) and 18 adults (56%) but only half in each group found these effective. Eight children (32%) were treated with erythromycin, with only two (25%) clearing, and one of these subsequently relapsing. In contrast, four adults (13%) received antibiotics, with three (75%) clearing and none relapsing thereafter. Ultraviolet B phototherapy was used in eight children (32%), with seven (88%) completely or almost clearing, but four (57%) subsequently relapsed. Fourteen adults (44%) received phototherapy; 10 (71%) completely cleared and only two of these (20%) subsequently relapsed. Strikingly, after a median disease duration of 30 months, only five children (20%) went into complete remission compared with 25 adults (78%) (P < 0.001). CONCLUSIONS: This is the first study to compare PL in children and adults. Our findings suggest that, compared with adults, PL in children is more likely to run an unremitting course, with greater lesional distribution, more dyspigmentation and a poorer response to conventional treatment modalities. PMID- 17854376 TI - The relationships between exposure dose and response in induction and elicitation of contact hypersensitivity in humans. AB - Like all physiological systems, the human immune system exhibits dose-response relationships in its reactions. The strength of sensitization is related to the potency of the immunogen and the dose that reaches the immune system. In skin, as sensitizing dose per unit area (mug cm(-2)) is increased on a log scale, there is a sigmoid dose-response curve for subsequent reactivity. Similarly, the response to elicitation shows a classical sigmoid response to increasing challenge dose, with the dose per unit area again being the determinant. There is a clear inverse correlation between the strength of sensitization and the subsequent dose of antigen to which an individual will respond. This is reflected in the different challenge systems used to diagnose the existence of allergic contact sensitization to a given allergen. The occluded patch test aims to use the highest concentration possible to detect the weakest degrees of allergy, whereas the repeated open application test uses much lower concentrations similar to those encountered in real life, applied repeatedly but without occlusion, to assess clinical relevance. Many authors have attempted to use the lowest concentrations to which rare, highly sensitized individuals can react to define the concentrations which might be free of risk in terms of inducing allergic sensitization. However, it is clear that the dose-response relationships for induction of sensitivity by repeated low-dose exposures must be carefully defined in future studies. This article reviews the dose-response relationships of human contact sensitization. PMID- 17854377 TI - Extensive skin pigmentation caused by deposits of metallic particles following total elbow arthroplasty: metallosis or not? PMID- 17854378 TI - The clinical effect of topical phenytoin on wound healing: a systematic review. AB - BACKGROUND: Oral phenytoin was first introduced as an antiseizure medication in 1937. Over 60 years investigators have shown an interest in how topical phenytoin may be used to promote wound healing in a variety of chronic wounds. OBJECTIVES: Systematically to identify, summarize and critically appraise the clinical evidence available on the effects of topical phenytoin on wound healing. METHODS: Systematic searches were carried out in PubMed (1963-2005), Medline (1966-2005) and Cinahl (1982-2005) for the years listed and in the Cochrane Library and the University of York NHS Centre for Reviews and Dissemination. The search terms used the following key words alone and in combination: phenytoin, wounds and injuries, wound healing, and wound care. Secondary hand searching was also carried out using relevant journal articles and reference lists, historical books, conference proceedings and theses in the area of wound healing. Papers were included if they described randomized controlled trials (RCTs) on humans and if the primary aim was wound closure, with a secondary aim of measuring wound healing over time. The methodological quality of the papers in this systematic review was assessed using the van Tulder method and in addition best-evidence synthesis was carried out. The magnitude of the effect of phenytoin therapy in the studies included in the systematic review was investigated in four of the 14 trials. RESULTS: Fourteen RCTs were included in the systematic review. Two papers were of high and 12 papers of low to moderate methodological quality. Most papers failed to describe randomization, treatment allocation and blinding techniques adequately. There was moderate evidence presented to support the use of phenytoin for the treatment of leg ulcers, leprosy wounds, chronic wounds and diabetic foot ulcers. There was a positive percentage treatment effect in favour of the phenytoin-treated group in one study investigating diabetic foot wounds and one study on chronic wounds. There was limited evidence for the use of phenytoin on burns and war wounds. CONCLUSIONS: Overall it would appear that studies investigating the effect of topical phenytoin on wound healing are of moderate methodological quality, and these suggest that there may be a positive effect on wound healing in a variety of wounds. PMID- 17854379 TI - Unusual molecular findings in Kindler syndrome. AB - Kindler syndrome (KS) is a rare inherited skin disorder with blistering and poikiloderma as its main clinical features. It is caused by loss-of-function mutations in the C20orf42 (KIND1) gene which encodes kindlin-1, an actin cytoskeleton-focal contact-associated protein which is predominantly expressed in keratinocytes. We investigated the molecular basis of KS in a 16-year-old Indian boy who had additional clinical findings, including scleroatrophic changes of the hands and feet, pseudoainhum and early onset of squamous cell carcinoma on his foot. Immunostaining for kindlin-1 in the patient's skin was completely absent and sequencing of C20orf42 (KIND1) genomic DNA showed a homozygous splice-site mutation at the -6 position, IVS9-6T-->A. Amplification and sequencing of cDNA from the skin revealed aberrant splicing with either deletion of exon 10 or deletion of exons 9, 10 and 11, both of which involve loss of the pleckstrin homology domain of kindlin-1 that is thought to play a role in cytoskeletal attachment and integrin-mediated cell signalling. Pathogenic splice-site mutations at the -6 position are unusual and have rarely been reported for any genetic disorder. Collectively, these findings extend the spectrum of clinical and molecular abnormalities in this rare genodermatosis. PMID- 17854380 TI - Missense mutation in exon 7 of TRPS1 gene in an Italian family with a mild form of trichorhinophalangeal syndrome type I. AB - BACKGROUND: Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant disorder, three types of which have been described in the literature. All of them are characterized by alopecia, facial dysmorphism and bone deformities. Deletions and nonsense mutations of the TRPS1 gene are responsible for most of the TRPS I and III cases with no clear genotype-phenotype correlation. The majority of missense mutations have been described at TRPS1 exon 6, encoding a presumptive GATA DNA-binding domain, and are known to be associated with the most severe forms of the phenotypic spectrum of TRPS. Mutation mapping at exon 7 described to date includes nonsense mutations and a familial case with an insertion mutation. OBJECTIVES: To determine a possible correlation between a mutation at exon 7 and mild TRPS phenotype. METHODS: We describe three members of an Italian family with TRPS I. All three showed clinical features typical of TRPS I such as temporal alopecia and facial abnormalities, but no mental retardation. RESULTS: Mutation analysis showed a missense mutation (R952C) in exon 7 of the TRPS1 gene. CONCLUSIONS: R952C is the first missense mutation described outside the GATA zinc finger domain of TRPS1. In contrast with missense mutations occurring within this region, this mutation prevents the transport of the TRPS1 protein into the nucleus, therefore determining TRPS I by haploinsufficiency. We hypothesize that a TRPS exon 7 mutation could result in a mild phenotype. PMID- 17854381 TI - Visible light induces matrix metalloproteinase-9 expression in rat eye. AB - Up-regulation of matrix metalloproteinase-9 (MMP-9, gelatinase B) in the nervous system has been demonstrated when excitotoxicity-induced tissue remodeling and neuronal death occurs. Induction of MMP-9 by a natural stimulus has not been observed yet. Using RT-PCR and gelatin-zymography we demonstrated MMP-9 induction at transcriptional and protein levels in different structures of the rat eye following over-stimulation with white light. MMP-9 elevation occurred in the retina without reduction in photoreceptor number or major anatomical reorganization. A transient decrease in electroretinogram b-wave indicated the functional recovery. Retrobulbar injection of a broad-spectrum MMP-inhibitor GM6001, slowed the recovery rate of b-wave amplitude. Even room-light applied to dark-adapted awake animals induced MMP-9 increase in the retina, which suggests a role for MMP-9 in physiological functional plasticity of the nervous system, such as light adaptation. This is the first demonstration of MMP-9 induction by a sensory stimulus. PMID- 17854382 TI - Reduced neuronal nitric oxide synthase is involved in ischemia-induced hippocampal neurogenesis by up-regulating inducible nitric oxide synthase expression. AB - Nitric oxide (NO), a free radical with signaling functions in the CNS, is implicated in some developmental processes, including neuronal survival, precursor proliferation, and differentiation. However, neuronal nitric oxide synthase (nNOS) -derived NO and inducible nitric oxide synthase (iNOS) -derived NO play opposite role in regulating neurogenesis in the dentate gyrus after cerebral ischemia. In this study, we show that focal cerebral ischemia reduced nNOS expression and enzymatic activity in the hippocampus. Ischemia-induced cell proliferation in the dentate gyrus was augmented in the null mutant mice lacking nNOS gene (nNOS-/-) and in the rats receiving 7-nitroindazole, a selective nNOS inhibitor, after stroke. Inhibition of nNOS ameliorated ischemic injury, up regulated iNOS expression, and enzymatic activity in the ischemic hippocampus. Inhibition of nNOS increased and iNOS inhibitor decreased cAMP response element binding protein phosphorylation in the ipsilateral hippocampus in the late stage of stroke. Moreover, the effects of 7-nitroindazole on neurogenesis after ischemia disappeared in the null mutant mice lacking iNOS gene (iNOS-/-). These results suggest that reduced nNOS is involved in ischemia-induced hippocampal neurogenesis by up-regulating iNOS expression and cAMP response element-binding protein phosphorylation. PMID- 17854383 TI - Neuronal nitric oxide synthase contributes to chronic stress-induced depression by suppressing hippocampal neurogenesis. AB - Increasing evidence suggests that depression may be associated with a lack of hippocampal neurogenesis. It is well established that neuronal nitric oxide synthase (nNOS)-derived NO exerts a negative control on the hippocampal neurogenesis. Using genetic and pharmacological methods, we investigated the roles of nNOS in depression induced by chronic mild stress (CMS) in mice. Hippocampal nNOS over-expression was first observed 4 days and remained elevated 21 and 56 days after exposure to CMS. The mice exposed to CMS exhibited behavioral changes typical of depression, and impaired neurogenesis in the hippocampus. The CMS-induced behavioral despair and hippocampal neurogenesis impairment were prevented and reversed in the null mutant mice lacking nNOS gene (nNOS-/-) and in the mice receiving nNOS inhibitor. Disrupting hippocampal neurogenesis blocked the antidepressant effect of nNOS inhibition. Moreover, nNOS /- mice exhibited antidepressant-like properties. Our findings suggest that nNOS over-expression in the hippocampus is essential for chronic stress-induced depression and inhibiting nNOS signaling in brain may represent a novel approach for the treatment of depressive disorders. PMID- 17854384 TI - Peptide transporter 2 (PEPT2) expression in brain protects against 5 aminolevulinic acid neurotoxicity. AB - The proton-coupled oligopeptide transporter PEPT2 (or SLC15A2) is the major protein involved in the reclamation of peptide-bound amino acids and peptide-like drugs in kidney. PEPT2 is also important in effluxing peptides and peptidomimetics from CSF at the choroid plexus, thereby limiting their exposure in brain. In this study, we report a neuroprotective role for PEPT2 in modulating the toxicity of a heme precursor, 5-aminolevulinic acid (5-ALA). Our findings demonstrate that in PEPT2-deficient mice, 5-ALA administration results in reduced survivability, a worsening of neuromuscular dysfunction, and CSF concentrations of substrate that are 8-30 times higher than that in wild-type control animals. The ability of PEPT2 to limit 5-ALA exposure in CSF suggests that it may also have relevance as a secondary genetic modifier of conditions (such as acute hepatic porphyrias and lead poisoning) in which 5-ALA metabolism is altered and in which 5-ALA toxicity is important. PMID- 17854385 TI - Circadian phosphorylation of ATF-2, a potential activator of Period2 gene transcription in the chick pineal gland. AB - Stimulus-induced transcription of the Period gene is a critical step for phase shift of vertebrate circadian systems. The promoter region of chicken Period2 contains a canonical calcium/cAMP-responsive element, but its functional relevance is not known. The present study shows that cAMP-responsive element binding protein (CREB) and activating transcription factor-2 (ATF-2) bind to the promoter region of the Period2 gene in the chick pineal gland. In transient transfection assays, a reporter construct containing 0.7-kbp upstream region of chicken Period2 was transactivated by ATF-2, but it was poorly responsive to CREB. In the chick pineal gland, phosphorylation of CREB protein at the kinase inducible domain was negatively regulated by light. On the other hand, phosphorylation of ATF-2 at the amino-terminal transactivation domain exhibited a circadian rhythm with a daytime peak, suggesting a role for ATF-2 in circadian rhythmicity in the chick pineal gland. PMID- 17854386 TI - The extracellular matrix in multiple sclerosis pathology. AB - The extracellular matrix (ECM) is a substrate upon which cells migrate, proliferate and differentiate. It is involved in the maintenance of cytoarchitecture, regulation of homeostasis, and it influences interactions between cells and molecules via specific receptors. Although a substantial body of knowledge has accumulated concerning the role of the ECM in peripheral tissues, little is known of the structure and function of the ECM in the CNS. However, marked changes in the expression of ECM constituents have been documented in various neurological disorders, including multiple sclerosis. This review focuses on the structure and function of the ECM in the CNS and in particular on the occurrence and involvement of ECM changes in the pathology of multiple sclerosis. Increased knowledge of the expression and functional role of ECM proteins in the CNS can lead to a better understanding of complex neurobiological processes both under normal as well as pathological conditions. PMID- 17854387 TI - Identification of NCAM-binding peptides promoting neurite outgrowth via a heterotrimeric G-protein-coupled pathway. AB - A combinatorial library of undecapeptides was produced and utilized for the isolation of peptide binding to the fibronectin type 3 modules (F3I-F3II) of the neural cell adhesion molecule (NCAM). The isolated peptides were sequenced and produced as dendrimers. Two of the peptides (denoted ENFIN2 and ENFIN11) were confirmed to bind to F3I-F3II of NCAM by surface plasmon resonance. The peptides induced neurite outgrowth in primary cerebellar neurons and PC12E2 cells, but had no apparent neuroprotective properties. NCAM is known to activate different intracellular pathways, including signaling through the fibroblast growth factor receptor, the Src-related non-receptor tyrosine kinase Fyn, and heterotrimeric G proteins. Interestingly, neurite outgrowth stimulated by ENFIN2 and ENFIN11 was independent of signaling through fibroblast growth factor receptor and Fyn, but could be inhibited with pertussis toxin, an inhibitor of certain heterotrimeric G proteins. Neurite outgrowth induced by trans-homophilic NCAM was unaffected by the peptides, whereas knockdown of NCAM completely abrogated ENFIN2- and ENFIN11 induced neuritogenesis. These observations suggest that ENFIN2 and ENFIN11 induce neurite outgrowth in an NCAM-dependent manner through G-protein-coupled signal transduction pathways. Thus, ENFIN2 and ENFIN11 may be valuable for exploring this particular type of NCAM-mediated signaling. PMID- 17854388 TI - Altered cerebral glucose and acetate metabolism in succinic semialdehyde dehydrogenase-deficient mice: evidence for glial dysfunction and reduced glutamate/glutamine cycling. AB - Succinic semialdehyde dehydrogenase (SSADH) catalyzes the NADP-dependent oxidation of succinic semialdehyde to succinate, the final step of the GABA shunt pathway. SSADH deficiency in humans is associated with excessive elevation of GABA and gamma-hydroxybutyrate (GHB). Recent studies of SSADH-null mice show that elevated GABA and GHB are accompanied by reduced glutamine, a known precursor of the neurotransmitters glutamate and GABA. In this study, cerebral metabolism was investigated in urethane-anesthetized SSADH-null and wild-type 17-day-old mice by intraperitoneal infusion of [1,6-(13)C(2)]glucose or [2-(13)C]acetate for different periods. Cortical extracts were prepared and measured using high resolution (1)H-[(13)C] NMR spectroscopy. Compared with wild-type, levels of GABA, GHB, aspartate, and alanine were significantly higher in SSADH-null cortex, whereas glutamate, glutamine, and taurine were lower. (13)C Labeling from [1,6 (13)C(2)]glucose, which is metabolized in neurons and glia, was significantly lower (expressed as mumol of (13)C incorporated per gram of brain tissue) for glutamate-(C4,C3), glutamine-C4, succinate-(C3/2), and aspartate-C3 in SSADH-null cortex, whereas Ala-C3 was higher and GABA-C2 unchanged. (13)C Labeling from [2 (13)C]acetate, a glial substrate, was lower mainly in glutamine-C4 and glutamate (C4,C3). GHB was labeled by both substrates in SSADH-null mice consistent with GABA as precursor. Our findings indicate that SSADH deficiency is associated with major alterations in glutamate and glutamine metabolism in glia and neurons with surprisingly lesser effects on GABA synthesis. PMID- 17854389 TI - High prevalence of cardiac hypertophy without detectable signs of fibrosis in patients with untreated active acromegaly: an in vivo study using magnetic resonance imaging. AB - OBJECTIVE: Left ventricular (LV) hypertrophy and myocardial fibrosis are considered the main pathological features of acromegalic cardiomyopathy. The aim of the study was to evaluate the proportion of LV hypertrophy and the presence of fibrosis in acromegalic cardiomyopathy in vivo using cardiac magnetic resonance (CMR). DESIGN AND PATIENTS: Fourteen consecutive patients (eight women, mean age 46 +/- 10 years) with untreated active acromegaly were submitted to two dimensional (2D) colour Doppler and integrated backscatter (IBS) echocardiography and CMR. MEASUREMENTS: LV volume, mass and wall thickness and myocardial tissue characterization (IBS and CMR). RESULTS: On echocardiography: mean LV mass (LVM) and LVM index (LVMi) were 209 +/- 48 g and 110 +/- 24 g/m(2), respectively; hypertrophy was revealed in five patients (36%); abnormal diastolic function [evaluated by isovolumic relaxation time (IVRT) or early (E) to late or atrial (A) peak velocities (E/A ratio)] was found in four patients (29%). Systolic function evaluated by measuring LV ejection fraction (LVEF) was normal (mean 72 +/- 12%) in all patients. Six patients (43%) had increased IBS (mean 57.4 +/- 6.2%). On CMR: mean LVM and LVMi were 151 +/- 17 g and 76 +/- 9 g/m(2), respectively; 10 patients (72%) had LV hypertrophy. Contrastographic delayed hyperenhancement was absent in all patients; on the contrary, mild enhancement was revealed in one patient. Systolic function was normal in all patients (LVEF 67 +/- 11%). LVMi was not related to serum IGF-1 concentrations or the estimated duration of disease. CONCLUSIONS: CMR is considered to be the gold standard for evaluating cardiac hypertrophy, fibrosis and systolic function. Using CMR, 72% patients with untreated active acromegaly had LV hypertrophy, which was only detected in 36% patients by echocardiography. However, cardiac fibrosis was absent in all patients irrespective of the estimated duration of disease. Although a very small increase in collagen content (as suggested by increased cardiac reflectivity at IBS), not detectable by CMR, could not be ruled out, it is unlikely that it would significantly affect cardiac function. PMID- 17854390 TI - Effects of the progestagen-only contraceptive implant Implanon on cardiovascular risk factors. AB - OBJECTIVE: Epidemiological studies on the cardiovascular risk of progestagen-only contraceptives are rare. With the present study we aimed to investigate the effect of the low-dose etonogestrel-releasing contraceptive implant Implanon on cardiovascular risk factors, including markers of inflammation. DESIGN: Longitudinal study. SETTING: Family planning centre of a University Hospital. SUBJECTS: Thirty-six healthy, nonsmoking women with regular cycles (n = 18 controls without hormonal contraception; n = 18 cases requesting the insertion of Implanon. MEASUREMENTS: Blood samples for the determination of C-reactive protein (CRP), nitric oxide (NO), sex hormones and plasma lipids were taken in the early follicular phase of the cycle in both groups. A second sample was taken 12 weeks after Implanon insertion or in the controls during the early follicular phase of cycle 4. RESULTS: Implanon treatment caused a 36% decrease in CRP (P < 0.06) and a significant decrease in high density lipoprotein (HDL) (P < 0.007), low density lipoprotein (LDL) (P < 0.001), cholesterol (P < 0.001), testosterone (P < 0.05) and SHBG (P < 0.002). Levels of NO, oestradiol and progesterone were not affected in either group. The cholesterol/HDL ratio did not change in Implanon carriers. There was a significant correlation between the cardiovascular risk factors CRP, cholesterol/HDL ratio and NO. CONCLUSION: The progestagen-only implant Implanon does not exert a negative effect on the cardiovascular risk factors CRP, cholesterol/HDL ratio and NO. These results suggest that the use of a progestagen only contraception does not increase cardiovascular risk factors in healthy young women. PMID- 17854391 TI - Analysis of gross deletions in the MEN1 gene in patients with multiple endocrine neoplasia type 1. AB - BACKGROUND: Mutation analysis with direct DNA sequencing is commonly used for the molecular diagnosis of multiple endocrine neoplasia type 1 (MEN1). However, a significant number of patients, despite clinical features of MEN1, do not show MEN1 mutations on direct DNA sequencing. Some of these patients may have gross gene deletions not detected by direct DNA sequencing or mutations in the noncoding regions of the gene not examined routinely. OBJECTIVE: To determine the prevalence of gross deletions in MEN1 in a large cohort of MEN1 patients. PATIENTS AND METHODS: During 1997-2006, we screened MEN1 mutations by direct DNA sequencing in 368 probands referred to our diagnostic molecular genetic laboratory. Of these, 101 probands (23 familial, 78 sporadic) fulfilled the clinical criteria for MEN1 (presence of at least two of the parathyroid, pancreatic or pituitary tumours) but were negative for mutations on DNA sequencing. Their DNA samples were examined for gross deletions of one or more exons of MEN1 by using multiple ligation-dependent probe amplification (MLPA) and long-range polymerase chain reaction (PCR) amplification. We also sequenced the minimal promoter region of MEN1 for mutations in the familial cases. RESULTS: We identified a gross deletion involving exons 5 and 6 of MEN1 in one proband (prevalence rate 1%). The sequencing of the minimal promoter region in the familial cases revealed no mutations. CONCLUSION: Gross deletion in the MEN1 gene is an uncommon cause of MEN1 and should be tested for in patients with a high clinical suspicion but without mutations on direct DNA sequencing. PMID- 17854392 TI - Obestatin and ghrelin levels in obese children and adolescents before and after reduction of overweight. AB - OBJECTIVES: Obestatin and ghrelin, which are derived from the same gene, are observed to have opposite effects on weight status. The aims of this study were to compare obestatin concentrations in obese and normal-weight children and to analyse the effect of weight loss on obestatin and ghrelin levels. METHODS: We examined anthropometrical markers and fasting serum obestatin, ghrelin, leptin, glucose and insulin concentrations in 44 obese children (mean age 11.2 years) before and after participating in a 1-year outpatient obesity intervention programme based on a high-carbohydrate, fat-reduced diet and increased physical activity. Additionally, total ghrelin, obestatin and leptin levels were determined in 22 normal-weight healthy children of similar age, gender and pubertal stage. RESULTS: Obestatin and leptin concentrations were significantly (P < 0.001) higher and ghrelin concentrations were significantly (P < 0.001) lower in obese children compared to nonobese children. In contrast to the 13 children without weight loss, substantial weight loss in 31 children led to a significant (P = 0.007) increase in obestatin and to a significant (P < 0.05) decrease in leptin and insulin concentrations, while ghrelin concentrations did not change significantly. Children with substantial weight loss demonstrated significantly (P = 0.009) lower obestatin and a tendency (P = 0.064) to higher ghrelin concentrations at baseline. Changes in insulin were not related to changes in ghrelin or obestatin. CONCLUSION: The increase in obestatin and the decrease in ghrelin in obese children point towards an adaptation process of weight status. Weight reduction due to a long-term lifestyle intervention resulted in an increase in obestatin levels. PMID- 17854393 TI - Hypovitaminosis D and parathyroid hormone response in the elderly: effects on bone turnover and mortality. AB - OBJECTIVE: To investigate whether absence of secondary hyperparathyroidism in the presence of hypovitaminosis D has altered bone turnover, fracture risk and mortality. DESIGN: A prospective cohort study. PATIENTS: A total of 1280 older men and women living in residential care facilities. MEASUREMENTS: We measured baseline serum 25-hydroxyvitamin D (25OHD), serum intact PTH, serum amino terminal propeptide of type I collagen (PINP) and serum carboxy-terminal telopeptide of type I collagen (CTX-I). Deaths and fractures were recorded prospectively. RESULTS: Hypovitaminosis D (25OHD < 39 nmol/l) and absence of secondary hyperparathyroidism (PTH > 7.0 pmol/l) in the presence of hypovitaminosis D were common in this sample with a prevalence of 77.5% and 53.3%, respectively. In the presence of hypovitaminosis D, residents showing a hyperparathyroid response (n = 406) had significantly higher serum bone turnover markers than individuals with serum PTH levels < or = 7.0 pmol/l (termed 'low vitamin D, normal PTH', n = 463). After adjusting for risk factors, mortality was significantly higher in the secondary hyperparathyroidism group than in the 'low vitamin D, normal PTH' group [hazard ratio (HR) = 1.35, 95% confidence interval (CI) 1.12-1.64; P = 0.002]. All residents with serum PTH levels < or = 7.0 pmol/l (n = 603) were similar with regard to both bone turnover and mortality, independent of their actual vitamin D status. CONCLUSION: Absence of secondary hyperparathyroidism in the presence of hypovitaminosis D appears to be common in the frail elderly and is associated with longer survival, similar to that observed in vitamin D-replete elderly subjects. PMID- 17854394 TI - Frequent mutations of beta-catenin gene in sporadic secreting adrenocortical adenomas. AB - OBJECTIVE: Molecular alterations remain largely unknown in most sporadic adrenocortical tumours and hyperplasias. In our previous work, we demonstrated the differential expression of several Wnt/beta-catenin signalling-related genes implicated in ACTH-independent macronodular adrenal hyperplasias (AIMAH). To better understand the role of Wnt/beta-catenin signalling in adrenocortical tumours, we performed mutational analysis of the beta-catenin gene. METHODS: We studied 53 human adrenocortical samples (33 adenomas, 4 carcinomas, 13 AIMAH, 3 ACTH-dependent adrenal hyperplasias) and the human adrenocortical cancer cell line NCI-H295R. All samples were screened for somatic mutations in exons 3 and 5 of the beta-catenin gene. Eleven and six samples were analysed for beta-catenin protein expression by Western blotting and immunohistochemistry, respectively. RESULTS: No mutations were detected in adrenocortical carcinomas, AIMAH and ACTH dependent hyperplasias. Genetic alterations were found in 5 (15%) out of 33 adenomas: three cortisol-secreting adenomas, one aldosterone-secreting adenoma and one nonfunctional adenoma. Two-point mutations occurred at serine residues of codons 37 and 45 (S37C and S45F). The remaining three tumours contained deletions of 6, 55 and 271 bp. H295R cells carry an activating S45P mutation. Western blot analysis of samples with 55- and 271-bp deletions showed an additional shorter and more intense band representing an accumulation of the mutated form of beta catenin protein. In addition, cytoplasmic and/or nuclear accumulation of beta catenin was observed in mutated adenomas by immunohistochemistry. CONCLUSIONS: Activating mutations of exon 3 of the beta-catenin gene are frequent in adrenocortical adenomas, and further characterization of the Wnt/beta-catenin signalling pathway should lead to a better understanding of adrenal tumourigenesis. PMID- 17854395 TI - Endocrine clinical update: where are we in the therapeutic management of pituitary-dependent hypercortisolism? PMID- 17854396 TI - Molecular characteristics in papillary thyroid cancers (PTCs) with no 131I uptake. AB - OBJECTIVE: Papillary thyroid cancers (PTCs) with no iodine uptake have an aggressive behaviour and a poor prognosis. The aim of our study was to characterize, at molecular level, a subset of PTC with no 131 iodine ((131)I) uptake. DESIGN AND METHODS: Forty-eight cancer tissues were divided into three groups: Group 1, 28 primary cancers; Group 2, 7 recurrences capable of trapping (131)I; and Group 3, 13 recurrences incapable of trapping (131)I. mRNA levels of thyroid genes (sodium/iodide symporter NIS, thyroglobulin, thyroperoxidase and pendrin) and glycolytic metabolism genes (GLUT-1, hexokinase I and II) and BRAF mutations were evaluated in the different groups. RESULTS: Cancers with no (131)I uptake had slightly reduced NIS, significantly reduced thyroglobulin (P < 0.01), thyroperoxidase (P = 0.01) and pendrin (P = 0.03) and significantly increased GLUT-1 (P = 0.01) gene expression levels; and a high frequency of BRAF mutations (77%). BRAF(V600E) mutation, in both primary and metastatic thyroid cancers, is associated with a marked drop in thyroperoxidase (29-fold) and pendrin (20-fold) expression and a considerable increase (five-fold) in GLUT-1 expression. CONCLUSIONS: (1) The loss of (131)I uptake in recurrences depends not only on a decrease in NIS gene, but possibly on a reduction in the molecules regulating its intracellular metabolism; (2) the high GLUT-1 gene expression supports the use of positron emission tomography with specific tracers in clinical management of such cancers; and (3) BRAF(V600E) point mutations may lead to less differentiated phenotypes, suggesting a worse prognosis. PMID- 17854397 TI - Combinatorial co-expression of pheromone receptors, V2Rs. AB - Basal neurons of the vomeronasal organ of the mouse express a superfamily of about 120 pheromone receptors, named V2Rs, that are grouped in four families, A, B, C, and D, according to sequence homology. Family-A, -B, and -D V2Rs are expressed as one receptor gene per cell, but we previously reported their co expression with family-C V2Rs. Here, we show that basal neurons can be further grouped according to the combinatorial expression of different V2Rs. Altogether, these findings suggest that in each basal neuron a transcriptional program is active for expressing a combination of two compatible receptors and for excluding, at the same time, the expression of all other V2Rs. Further analyses revealed non-random combinations of co-expression between family-C V2Rs and genes of the class Ib major histocompatibility complex. Thus, each basal neuron of the vomeronasal organ represents a highly qualified sensory unit for detecting very specific combinations of pheromonal cues. PMID- 17854398 TI - Important differences between human and mouse APOE gene promoters: limitation of mouse APOE model in studying Alzheimer's disease. AB - Apolipoprotein E (ApoE), encoded by the apolipoprotein E gene (APOE), plays an important role in the pathogenesis of Alzheimer's disease (AD). The APOE epsilon4 variant is strongly associated with AD. APOE promoter polymorphisms have also been reported to associate with higher AD risk. Mouse models of APOE expression have long been used to study the pathogenesis of AD. Elucidating the role of the APOE gene in AD requires understanding of how its regulation differs between mouse and human APOE genes, and how the differences influence AD risk. We compared the structure and function of both the human APOE gene promoter (hAPOEP) and mouse APOE gene promoter (mAPOEP) regions. Homology is less than 40% at 180 bp or more upstream of the two species' transcription start site (TSS, +1). Functional analysis revealed both similarities and important differences between the two sequences, significantly affected by human versus rodent cell line origin. We likewise probed nuclear extracts from several cell lines of different origins (astrocytic, glial, and neuronal) and mouse brain with specific hAPOEP and mAPOEP fragments. Each fragment shared DNA-protein interactions with the other but, notably, also bound distinct factors, demonstrated by gel shift and southwestern analyses. We determined possible identities for these distinct factors. These results suggest that regulation of mouse and human APOE genes may be sufficiently unique to justify the use of both the human APOE promoter sequence in transgenic rodent models and non-rodent AD models for studying factors involved in AD pathogenesis. PMID- 17854399 TI - Two new anamorphic yeasts, Candida thailandica sp. nov. and Candida lignicola sp. nov., isolated from insect frass in Thailand. AB - Two new yeast strains of the genus Candida were isolated from insect frass collected in Khao-Yai National Park, Nakhonrachasima, Thailand. Based on the morphological, physiological and chemotaxonomic characteristics, and sequence analysis of the D1/D2 domain of 26S rRNA gene, these two strains were found to represent two distinct undescribed species and were named Candida thailandica sp. nov. (ST-17 = BCC 7717(T) = NBRC 102562(T)=CBS 10 610) and Candida lignicola sp. nov. (ST-33 = BCC 7733(T) = NBRC 102564(T) = CBS 10612). In the D1/D2 domain of 26S rRNA gene, C. thailandica (GeneBank accession no. AY228491) differs from Candida tsuchiyae, the nearest species, in 66 nucleotide substitutions (10%) and C. lignicola (GeneBank accession no. AY845350) differs from Candida coipomoensis, the nearest species, in nine nucleotides (1.6%). These two new species are clearly distinguished from their closest species by the assimilation of several carbon compounds. PMID- 17854400 TI - The Porphyromonas gingivalis clpB gene is involved in cellular invasion in vitro and virulence in vivo. AB - ClpB, a component of stress response in microorganisms, serves as a chaperone, preventing protein aggregation and assisting in the refolding of denatured proteins. A clpB mutant of Porphyromonas gingivalis W83 demonstrated increased sensitivity to heat stress, but not to hydrogen peroxide and extreme pHs. In KB cells, human coronary artery endothelial (HCAE) cells and gingival epithelial cells, the clpB mutant exhibited significantly decreased invasion suggesting that the ClpB protein is involved in cellular invasion. Transmission electron microscopic analysis showed that the clpB mutant was more susceptible to intracellular killing than the wild-type strain in HCAE cells. The global genetic profile of the clpB mutant showed that 136 genes belonging to several different cellular function groups were differentially regulated, suggesting that ClpB is ultimately involved in the expression of multiple P. gingivalis genes. A competition assay in which a mixture of wild-type W83 and the clpB mutant were injected into mice demonstrated that the clpB mutant did not survive as well as the wild type. Additionally, mice treated with the clpB mutant alone survived significantly better than those treated with the wild-type strain. Collectively, these data suggest that ClpB, either directly or indirectly, plays an important role in P. gingivalis virulence. PMID- 17854401 TI - Computerized assessment of cognitive impairment in narcoleptic patients. AB - OBJECTIVES - This study was aimed to investigate the comprehensive range of cognitive performance using the objective computerized assessment system in narcolepsy and age, gender, and IQ-matched healthy comparison. MATERIALS AND METHODS - The cognitive functions of 24 patients with narcolepsy and 24 healthy comparison subjects were assessed. RESULTS - Narcoleptics performed more frequent omission and commission errors in the vigilance test, and more frequent omission errors in the continuous performance test. Narcoleptics' response time was slower than healthy volunteers, and the differences were more exaggerated in more complex tasks. The simple repetitious working performance was more impaired in the narcoleptic subjects than in healthy comparison subjects. Narcolepsy group showed worse performances in the determination unit than the comparison group, and this impairment became more salient in faster stimuli relative to slower ones. CONCLUSIONS - Narcoleptics have deficits of efficiency in attention allocation and execution as well as simple vigilance problem. PMID- 17854403 TI - Transcriptional control of nmrA by the bZIP transcription factor MeaB reveals a new level of nitrogen regulation in Aspergillus nidulans. AB - Fungi can use a diverse range of nitrogen sources. Some nitrogen sources sustain a rapid growth rate and are used in preference to less readily metabolized nitrogen sources. The mechanisms involved in this control of nitrogen utilization have been studied in the model filamentous ascomycete, Aspergillus nidulans. The GATA transcription factor AreA is necessary for the expression of nitrogen catabolic permeases and enzymes. AreA activity is controlled by multiple mechanisms including regulated areA transcript levels and regulated AreA nuclear export. During nitrogen sufficiency, AreA activation is also prevented by the co repressor NmrA. We have investigated nitrogen signalling to NmrA. NmrA overexpression prevents AreA function irrespective of the nitrogen status. The mRNA levels of areA and nmrA are inversely regulated, suggesting that the relative levels of AreA and NmrA are critical in determining AreA activation. The bZIP transcription factor MeaB was found to activate nmrA expression and a conserved element, TTGCACCAT, bound by MeaB in vitro is present in the promoters of NmrA homologues in other filamentous ascomycetes. Expression of meaB was not strongly regulated suggesting that transcriptional activation by MeaB is modulated by the nitrogen status. This work highlights a new level of complexity in the regulation of nitrogen catabolism. PMID- 17854402 TI - The role of iron in Mycobacterium smegmatis biofilm formation: the exochelin siderophore is essential in limiting iron conditions for biofilm formation but not for planktonic growth. AB - Many species of mycobacteria form structured biofilm communities at liquid-air interfaces and on solid surfaces. Full development of Mycobacterium smegmatis biofilms requires addition of supplemental iron above 1 microM ferrous sulphate, although addition of iron is not needed for planktonic growth. Microarray analysis of the M. smegmatis transcriptome shows that iron-responsive genes - especially those involved in siderophore synthesis and iron uptake - are strongly induced during biofilm formation reflecting a response to iron deprivation, even when 2 microM iron is present. The acquisition of iron under these conditions is specifically dependent on the exochelin synthesis and uptake pathways, and the strong defect of an iron-exochelin uptake mutant suggests a regulatory role of iron in the transition to biofilm growth. In contrast, although the expression of mycobactin and iron ABC transport operons is highly upregulated during biofilm formation, mutants in these systems form normal biofilms in low-iron (2 microM) conditions. A close correlation between iron availability and matrix-associated fatty acids implies a possible metabolic role in the late stages of biofilm maturation, in addition to the early regulatory role. M. smegmatis surface motility is similarly dependent on iron availability, requiring both supplemental iron and the exochelin pathway to acquire it. PMID- 17854404 TI - The LysR-type regulator AtzR binding site: DNA sequences involved in activation, repression and cyanuric acid-dependent repositioning. AB - The LysR-type transcriptional regulator (LTTR) AtzR of Pseudomonas sp. strain ADP activates the cyanuric acid-utilization atzDEF operon in response to low nitrogen availability and the presence of cyanuric acid. AtzR also represses expression of its own gene, atzR, transcribed divergently from atzDEF. Here we identify and functionally characterize the cis-acting sequences at the atzR-atzDEF divergent promoter region required for AtzR-dependent regulation. AtzR binds a single site overlapping both the PatzR and PatzDEF promoters and induces a DNA bend immediately upstream from PatzDEF. Interaction of AtzR with the inducer cyanuric acid shortens the protein-DNA interaction region and relaxes the DNA bend. The AtzR binding site contains a strong binding determinant, the repression binding site (RBS), centred at position -65 relative to the atzDEF transcriptional start, containing the LTTR binding consensus motif. Integrity of the RBS is essential for high-affinity AtzR binding, activation and autorepression. A second, weaker binding determinant, the activation binding site (ABS), is present between the RBS and PatzDEF. Deletion of the ABS only provokes a modest decrease in AtzR affinity for the promoter region in vitro, but abolishes repression of PatzR in vivo. Involvement of the ABS in autorepression has not been previously reported. PMID- 17854405 TI - The cell wall: a carbohydrate armour for the fungal cell. AB - The cell wall is composed of a polysaccharide-based three-dimensional network. Considered for a long time as an inert exoskeleton, the cell wall is now seen as a dynamic structure that is continuously changing as a result of the modification of culture conditions and environmental stresses. Although the cell wall composition varies among fungal species, chemogenomic comparative analysis have led to a better understanding of the genes and mechanisms involved in the construction of the common central core composed of branched beta1,3 glucan chitin. Because of its essential biological role, unique biochemistry and structural organization and the absence in mammalian cells of most of its constitutive components, the cell wall is an attractive target for the development of new antifungal agents. Genomic as well as drug studies have shown that the death of the fungus can result from inhibition of cell wall polysaccharide synthases. To date, only beta1,3 glucan synthase inhibitors have been launched clinically and many more targets remain to be explored. PMID- 17854406 TI - Metabolic engineering of morphinan alkaloids by over-expression and RNAi suppression of salutaridinol 7-O-acetyltransferase in opium poppy. AB - We demonstrate that both over-expression and suppression of the gene encoding the morphinan pathway enzyme salutaridinol 7-O-acetyltransferase (SalAT) in opium poppy affects the alkaloid products that accumulate. Over-expression of the gene in most of the transgenic events resulted in an increase in capsule morphine, codeine and thebaine on a dry-weight basis. The transgenic line with the highest alkaloid content had 41%, 37% and 42% greater total alkaloids than the control in three independent trials over 3 years. DNA-encoded hairpin RNA-mediated suppression of SalAT resulted in the novel accumulation of the alkaloid salutaridine at up to 23% of total alkaloid; this alkaloid is not detectable in the parental genotype. Salutaridine is not the substrate of SalAT but the substrate of the previous enzyme in the pathway, salutaridine reductase. RNA transcript analysis of 16 primary T0 transformants and their segregating T1 progeny revealed an average reduction in SalAT transcript to about 12% of the control. Reduction in SalAT transcript was evident in both leaves and latex. Reverse transcriptase PCR and high-performance liquid chromatography analyses confirmed cosegregation of the expressed transgene with the salutaridine accumulating phenotype. PMID- 17854407 TI - High perinatal seroprevalence of cytomegalovirus in northern Taiwan. AB - AIM: The living style, health-care system and socio-economic environments have changed substantially in Taiwan over past 20 years. This study was aimed to estimate the current perinatal cytomegalovirus (CMV) seroprevalence in northern Taiwan. METHODS: In a Taiwan Birth Panel Study, 483 pairs of mothers and neonates were prospectively recruited from one tertiary medical center, one local hospital, and two obstetric clinics located in northern Taiwan from April 2004 through January 2005. Sera of their paired maternal and cord blood were tested by an enzyme-linked immunosorbent assay method for CMV IgG and IgM antibodies. Additional data were collected for health measures and epidemiological characteristics through trained interviewers utilising structured questionnaires. RESULTS: Among 483 mothers studied, 93% were Taiwanese, 6.4% were immigrants from the south-eastern Asia and Mainland China, and 0.6% was aborigines. The seropositive rate of CMV IgG and IgM among the mothers was 91.1% and 3.5%, respectively. The immigrant mothers and the mothers younger than 20 years of age had a higher IgM seroprevalence (P < 0.05). Furthermore, 90.8% of the offspring had CMV IgG seropositivity and yet none of the neonates were CMV IgM positive. CONCLUSION: The seroprevalence of CMV among childbearing women is high in northern Taiwan. The immigrant mothers and the teenage mothers appear to have higher seropositivity of CMV IgM. PMID- 17854408 TI - Fulminant mitral regurgitation due to ruptured chordae tendinae in acute rheumatic fever. AB - AIMS: Description of the presentation and management of cases of fulminant mitral regurgitation in acute rheumatic fever (ARF). METHODS: Retrospective case series of 4 children, aged 6-10 years, presenting in acute pulmonary oedema because of rupture of elongation of the chordae tendinae of the mitral valve leading to flail leaflets and severe mitral regurgitation. RESULTS: Urgent cardiac surgery with mitral valve repair was performed. Resolution of heart failure was achieved in each case. The difficulties in diagnosis and management of this uncommon and often unrecognised presentation of ARF are discussed. CONCLUSIONS: Cardiac surgery can be life saving for fulminant mitral regurgitation due to rupture of chordae tendinae of the mitral valve in ARF. PMID- 17854409 TI - High volume-low intensity exercise camp and glycemic control in diabetic children. AB - AIM: To evaluate the effects of the designed regime encompassing high volume-low intensity physical activity programme on glycemic control in diabetic children, 20 subjects (age 12.81 +/- 2.14) spent 2 weeks in a controlled environment of a summer camp. METHODS: An exercise physiologist and a kinesiology specialist programme and conducted the three exercise sessions a day. Total daily caloric intake was controlled and the blood glucose was monitored four times a day with special concern for hypoglycaemia episodes. Short and long-term effects (HbA1c) of the summer camp were evaluated 10 days and 2 months following programme completion. The insulin dosage was not lowered at the beginning of the camp for everyone, but it was individually modified according to the blood glucose monitoring. RESULTS: Initial HbA1c was 8.28 +/- 1.3% and decreased to 7.92 +/- 1.42% measured 10 days after the camp (P = 0.023) while the number of children with the satisfactory HbA1c level lower than 7.5% doubled. HbA1c increased again 2 months following the camp. The average blood glucose concentrations decreased in the last days of the camp when compared with the first day in three out of four daily measurements (P < 0.05). There were only two clinically manifested hypoglycaemia episodes recorded. CONCLUSION: With a low rate of hypoglycaemia crisis and better glycemic control the proposed programme was found to be satisfactory but the downside was that the duration of the effects was too short. With no participation in organised exercise programmes and with absence of controlled nutrition, the beneficial effects of the camp disappeared within 2 months after the camp. PMID- 17854410 TI - Increased prevalence of constipation in pre-school children is attributable to under-consumption of plant foods: A community-based study. AB - AIM: To evaluate consumption of foods rich in dietary fibre and its relation to the prevalence of constipation in pre-school children. METHODS: In total, 368 children aged 3-5 years were randomly selected from kindergartens in Hong Kong. Constipation was confirmed by Rome-criteria. Children with normal bowel habits served as non-constipated controls. Consumption of vegetables, fruits, whole grain cereals and fluid were determined using a 3-day food record. RESULTS: A total of 28.8% children were reported to have constipation. Median dietary fibre intake of constipated children was significantly lower than non-constipated children (3.4 g/d (inter-quartile range (IQR): 2.3-4.6 g/d) vs. 3.8 g/d (IQR: 2.7 4.9 g/d); P = 0.044) corresponding to 40% reference dietary fibre intake. Constipated children also had significantly lower intakes of vitamin C (P = 0.041), folate (P = 0.043) and magnesium (P = 0.002). Fruit intake and total plant foods intake were significantly lower in the constipated than non constipated children: (61 g/d (IQR: 23.8-115 g/d) vs. 78 g/d (IQR: 41.7-144.6 g/d); P = 0.047) and (142.5 g/d (IQR: 73.7-214.7 g/d) vs. 161.1 g/d (IQR: 98.3 233.3 g/d); P = 0.034), respectively. Total fluid intake did not differ between groups but milk intake among the constipated children was marginally higher than the non-constipated children (P = 0.055) CONCLUSION: Insufficient dietary fibre intake is common in Hong Kong pre-school children. Constipated children had significantly lower intakes of dietary fibre and micronutrients including vitamin C, folate and magnesium than non-constipated counterparts which was attributable to under-consumption of plant foods. However, milk intake was marginally higher in the constipated children. More public education is necessary for parents to help develop healthy dietary habit and bowel habit in early life in order to prevent childhood constipation. PMID- 17854411 TI - Effect of single loading dose of intravenous caffeine infusion on superior mesenteric artery blood flow velocities in preterm infants. AB - AIM: To evaluate the effects of a single loading dose of caffeine base (10 mg/kg) on superior mesenteric artery (SMA) blood flow velocities (BFV). METHODS: Eighteen preterm infants of gestational age 30 mmHg had DKA (sensitivity 1.0, specificity 0.86). Six patients with an ETCO(2) < 30 mmHg did not have DKA. CONCLUSIONS: Nasal capnography in conjunction with clinical assessment is predictive of DKA. Further research into this area with larger numbers could help validate ETCO(2) as a screening tool for DKA in the emergency department. PMID- 17854453 TI - Impact of implementation of Integrated Management of Childhood Illness on improvement of health system in China. AB - AIM: To explore the impact of implementation of the Integrated Management of Childhood Illness (IMCI) strategy on the Chinese health system. METHODS: Pre- and post-intervention field surveys, based on the adapted World Health Organization protocol of health facility surveys and follow-up assessment tools, respectively. Three hundred and forty-five health facilities were investigated pre intervention and 74 health facilities post intervention. Observation of case management of health workers, interviews with mothers and systematic checking of equipment and drug supplies were conducted in both pre- and post-intervention surveys. RESULTS: There were significant improvements demonstrated with implementation of the IMCI strategy in terms of rational use of drugs, provision of basic equipment and drug supplies of both township and village facilities. The inappropriate use of drugs significantly decreased: injection/IV (from 43.6% to 2.7%), antibiotics (from 59.3% to 6.2%) and hormones (from 4.9% to 0). The availability of basic equipment and supplies of health facilities was improved greatly: children's scales (from 27.8% to 90.5%), timing devices (from 89.3% to 97.3%) and utilities for mixing oral rehydration salts (ORS) (from 36.5% to 100.0%). The supply of all recommended drugs increased, with ORS, vitamin A/D, iron, tetracycline eye ointment, vitamin B complex and diazepam increased greatly. CONCLUSIONS: The IMCI strategy has been shown to contribute to the improvement of the health system, promoting the efficient management of medical care at township and village level, as well as improving the relationship between doctors and patients. PMID- 17854454 TI - Unintentional paediatric ingestions of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists. AB - AIMS: There is limited information on safety of angiotensin converting enzyme (ACE) inhibitors and angiotensin II (AII) receptor antagonists in unintentional paediatric ingestions. This study was conducted with the aim of developing referral guidelines for poison information centres. METHODS: Calls to the NSW poison information centre from January 2002 to July 2004 regarding paediatric ingestion of ACE inhibitors and AII receptor antagonists were recruited and prospectively followed up. Information collected included: demographics (age, gender, weight), type of exposure (unintentional, therapeutic error), ingested dose and clinical effects. Dose was reported in defined daily doses (DDD) to compare across and within the two drug classes with respect to the normal adult dose. RESULTS: Nineteen cases of paediatric ingestion of ACE inhibitors and AII receptor antagonists were included. The median age was 2 years (Interquartile range (IQR): 20-33 months) and the median dose ingested was 1 DDD (IQR: 1-2). There were nine ACE inhibitor ingestions and 10 AII receptor antagonist ingestions. One of nine children (11%) observed in hospital developed transient hypotension but required no treatment and recovered without complication. This child ingested an ACE inhibitor and ingested >3 DDD. CONCLUSION: Unintentional paediatric ingestions of ACE inhibitors and AII receptor antagonists resulted in the majority of children remaining asymptomatic. ACE inhibitor ingestions under 2 DDD can be observed at home provided the child is asymptomatic and there is a responsible adult to observe the child. The dose required for observation in AII receptor antagonist ingestions is less clear. PMID- 17854455 TI - Parasitic infestation and nutritional status among schoolchildren in Vientiane, Lao PDR. AB - AIMS: To investigate the prevalence of intestinal parasitic infestation among school-aged children residing in Vientiane capital city; and to assess the impact of its infestation on nutrition status of those children. METHODS: The school based cross-sectional study was conducted from December 2005 to February 2006. The systemic random samplings were employed to select schools and schoolchildren. Five hundred and thirty-six schoolchildren (350 high-school children and 186 parents of elementary-school children) were completely interviewed by semistructured questionnaire and performed anthropometric measurement. The direct faecal smear was employed to analyse 299 (55.8%) stool samples. The SPSS version 12.01 and Epi Info version 6.0 were used for data analysis. RESULTS: The overall prevalence of parasitic infestation was 38.1%, with 18.1% of Opisthorchis viverrini and 14.7% of Ascaris lumbricoides. The prevalences of stunting and underweight were 20.2% and 20.0%, respectively. The prevalences of stunting (OR = 3.28; P < 0.01) and underweight (OR = 2.69; P < 0.05) were higher among high school children who were infested by intestinal parasites. CONCLUSION: Approximately one-third of schoolchildren in Vientiane capital city were infested by intestinal parasites. The persistent parasitic infestation seemed to be associated with growth rate pattern among those children. School-based parasite control programme and health promotion are needed to eliminate this major public health problem in Lao People Democratic Republic. PMID- 17854456 TI - Health needs of Australian children living in out-of-home care. AB - BACKGROUND: Children living in out-of-home care have high and frequently unidentified health needs. The Child Protection Unit at Sydney Children's Hospital offers comprehensive health screening to children in care. AIMS: To report the experience of the health screening clinic and the rates of identified health problems of children in care in this sample, and to compare these rates with the general child population and children in care overseas. METHODS: Comprehensive multidisciplinary health screens were offered to children in out-of home care. RESULTS: High rates of physical, developmental and emotional health problems were identified. The rates of poor health were greater than the average child population of New South Wales, but similar to the rates of poor health reported in children in care overseas. CONCLUSIONS: Children in care are a vulnerable group of the child population who experience unacceptable levels of poor health. Comprehensive health screens can help identify previously undetected health problems. PMID- 17854457 TI - Failure to distinguish systemic-onset juvenile idiopathic arthritis from incomplete Kawasaki disease in an infant. AB - In an infant, an initial diagnosis of incomplete Kawasaki disease was made according to the American Heart Association guidelines. However, the diagnosis of systemic-onset juvenile idiopathic arthritis was established later. Physicians need to recognize that systemic-onset juvenile idiopathic arthritis can be mistaken for incomplete Kawasaki disease, even when the guidelines are used. PMID- 17854458 TI - Colon perforation due to pathologic aerophagia in an intellectually disabled child. AB - Aerophagia, characterized by symptoms related to repetitive swallowing of air, is a functional gastrointestinal disorder. In some cases, severe aerophagia causes massive bowel distention and leads to volvulus, ileus, and even intestinal necrosis and perforation. A 10-year-old intellectually disabled boy was referred to our unit due to severe abdominal distention, bilious vomiting, no passage of feces and flatus during the previous 3 days. He had experienced episodes of severe abdominal distention and flatulence over the past 2-3 years. In the exploratory laparotomy, two old colonic perforations were found. Splenic flexura resection and diverting colostomy were performed. Rectal biopsy showed ganglionic architecture. During the fifth postoperative month, he was admitted to the emergency unit with severe abdominal distention. During this visit, we observed him swallowing air. For this reason, his primary illness was diagnosed as a pathologic aerophagia. The colostomy was closed 11 months following the first operation. His parents did not accept gastrostomy as a desufflator. For this reason, they were taught nasogastric tube installation for gastric distention. Briefly, if abdominal distention increases during the course of the day and increased flatus is observed during sleep, aerophagia could be the primary pathology. If aerophagia could cause complications, gastrostomy should be applied. If the parents refuse gastrostomy, the parents could perform nasogastric tube drainage. PMID- 17854459 TI - Herpes zoster due to Oka vaccine strain of varicella zoster virus in an immunosuppressed child post cord blood transplant. AB - A 5-year-old boy was vaccinated with the Oka strain of varicella zoster virus vaccine before cord blood transplant for chronic granulomatous disease in 2005. In 2006, he developed herpes zoster on his left arm. DNA from the vesicular rash confirmed the Oka vaccine strain of varicella zoster virus caused this complication. He responded well to 10 days of aciclovir treatment. PMID- 17854460 TI - Congenital rubella syndrome, hyper-IgM syndrome and autoimmunity in an 18-year old girl. AB - Congenital rubella syndrome can be associated with disgammaglobulinaemia and autoimmune phenomena in adult and paediatric population. The aim of this article is to present the association between a congenital rubella syndrome with hypogammaglobulinaemia and hyper IgM diagnosed at the age of 8 months and autoimmune manifestations in an 18-year-old girl. A medical chart review of this patient since admission at our institution at 8 months of age was carried out. During infancy she presented the classical manifestations of a rubella syndrome (sensorineural deafness and brain calcifications in basal ganglia) with respiratory and gastrointestinal infections. She was also diagnosed of localised scleroderma and thyroiditis. She has been on intravenous immunoglobulin since diagnosis, with rapid normalisation of IgG and IgM levels, decreased incidence of infectious processes, but with persistent autoimmune phenomena. At 18 years of age she was admitted because of a thyroid mass. Fine needle aspiration biopsy was not conclusive and thyroidectomy was performed. Pathology studies showed no malignancy. She is now on replacement therapy with thyroid hormones. Our aim is to emphasise the importance of the association between autoimmune phenomena in patients with immunodeficiencies, even secondary to some infections, and the increased frequency of malignancies owing to the persistent immunologic defect in this syndrome. PMID- 17854464 TI - Reconsidering the increase of expression of GGT in alcoholic liver diseases. PMID- 17854465 TI - Hepatic iron accumulation may be associated with insulin resistance in patients with chronic hepatitis C. AB - BACKGROUND/AIM: Insulin resistance and hepatic iron overload are frequently demonstrated in hepatitis C virus (HCV)-related liver diseases. We investigated the relationship between insulin resistance and hepatic iron deposition in patients with chronic HCV infection. METHODS: Insulin resistance was evaluated using the homeostasis model assessments for insulin resistance (HOMA-IR) in 56 non-diabetic non-obese patients with biopsy proven chronic hepatitis C. The relationship between insulin resistance and serum ferritin levels or the grade of hepatic iron deposition was assessed. RESULTS: The levels of plasma immunoreactive insulin (IRI) and HOMA-IR were significantly correlated with serum ferritin levels and the grade of hepatic iron deposition (P = 0.003).Although IRI and HOMA-IR increased in parallel with the development of hepatic fibrosis, insulin resistance (HOMA-IR > 2) was observed in 11 (26.2%) of 42 patients even without severe fibrosis (F0-2). Among patients without severe fibrosis, IRI and HOMA-IR were significantly higher in patients with iron deposits than in those without iron deposits. CONCLUSION: Hepatic iron overload may be associated with insulin resistance in patients with chronic hepatitis C, especially in patients with mild to moderate fibrosis. PMID- 17854463 TI - Regulatory processes interacting to maintain hepatic blood flow constancy: Vascular compliance, hepatic arterial buffer response, hepatorenal reflex, liver regeneration, escape from vasoconstriction. AB - Constancy of hepatic blood flow (HBF) is crucial for several homeostatic roles. The present conceptual review focuses on interrelated mechanisms that act to maintain a constant HBF per liver mass. The liver cannot directly control portal blood flow (PF); therefore, these mechanisms largely operate to compensate for PF changes. A reduction in PF leads to reduced intrahepatic distending pressure, resulting in the highly compliant hepatic vasculature passively expelling up to 50% of its blood volume, thus adding to venous return, cardiac output and HBF. Also activated immediately upon reduction of PF are the hepatic arterial buffer response and an HBF-dependent hepatorenal reflex. Adenosine is secreted at a constant rate into the small fluid space of Mall which surrounds the terminal branches of the hepatic arterioles, portal venules and sensory nerves. The concentration of adenosine is regulated by washout into the portal venules. Reduced PFreduces the washout and the accumulated adenosine causes dilation of the hepatic artery, thus buffering the PF change. Adenosine also activates hepatic sensory nerves to cause reflex renal fluid retention, thus increasing circulating blood volume and maintaining cardiac output and PF. If these mechanisms are not able to maintain total HBF, the hemodynamic imbalance results in hepatocyte proliferation, or apoptosis, by a shear stress/nitric oxide dependent mechanism, to adjust total liver mass to match the blood supply. These mechanisms are specific to this unique vascular bed and provide an excellent example of multiple integrative regulation of a major homeostatic organ. PMID- 17854466 TI - Hepatic expression of gamma-glutamyltranspeptidase in the human liver of patients with alcoholic liver disease. AB - BACKGROUND: Gamma-glutamyltranspeptidase (GGT) has been recognized as an enzyme that converts glutathione into cysteine, and it is localized predominantly within the liver. Serum GGT is clinically recognized as the most useful marker for diagnosis of alcoholic liver disease (ALD). METHODS: GGT localization within the liver was examined immunohistochemically using an anti-GGT antibody and was visualized by confocal laser scanning microscopy in ALD and normal livers. Double immunostaining for GGT and dipeptidylpeptidase-IV (DPP-IV) was carried out to evaluate GGT localization in greater detail. RESULTS: Expression of GGT protein and mRNA was studied with immunoblot analysis and in situ hybridization, respectively. Immunohistochemically, the expression of GGT in the normal liver was faintly demonstrated in the bile canaliculi of hepatocytes and in biliary epithelial cells. In ALD livers, GGT was clearly demonstrated at the same sites. Double immunostaining demonstrated that GGT and DPP-IV were colocalized in hepatocytes in the ALD liver. In situ hybridization clearly demonstrated GGT-mRNA within the cytoplasm of hepatocytes and biliary epithelial cells. Immunoblot analysis revealed that GGT protein expression was increased in the ALD livers compared with that seen in the normal livers. CONCLUSION: These findings indicate that GGT in control and alcoholic livers is synthesized in hepatocytes and biliary epithelial cells, and is localized within the bile canalicular membrane and the luminal membrane in those cells, respectively. In conclusion, GGT synthesis and protein expression are increased in ALD livers, leading to the elevation of serum levels of GGT that are commonly noted in patients with the disease. PMID- 17854467 TI - Erratum. PMID- 17854468 TI - The role of Hansenula polymorpha MIG1 homologues in catabolite repression and pexophagy. AB - In the methanol-utilizing yeast Hansenula polymorpha, glucose and ethanol trigger the repression of peroxisomal enzymes at the transcriptional level, and rapid and selective degradation of methanol-induced peroxisomes by means of a process termed pexophagy. In this report we demonstrate that deficiency in the putative H. polymorpha homologues of transcriptional repressors Mig1 (HpMig1 and HpMig2), as well as HpTup1, partially and differentially affects the repression of peroxisomal alcohol oxidase by sugars and ethanol. As reported earlier, deficiency in HpTup1 leads to impairment of glucose- or ethanol-induced macropexophagy. In H. polymorpha mig1mig2 double-deletion cells, macropexophagy was also substantially impaired, whereas micropexophagy became a dominant mode of autophagic degradation. Our findings suggest that homologues of the elements of the Saccharomyces cerevisiae main repression pathway have pleiotropic functions in H. polymorpha. PMID- 17854469 TI - In vivo prediction of the nutrient status of individual microalgal cells using Raman microspectroscopy. AB - An in vivo method for predicting the nutrient status of individual algal cells using Raman microspectroscopy is described. Raman spectra of cells using 780 nm laser excitation show enhanced bands mainly attributable to chlorophyll a and beta-carotene. The relative intensities of chlorophyll a and beta-carotene bands changed under nitrogen limitation, with chlorophyll a bands becoming less intense and beta-carotene bands more prominent. Although spectra from N-replete and N starved cell populations varied, each distribution was distinct enough such that multivariate classification methods, such as partial least squares discriminant analysis, could accurately predict the nutrient status of the cells from the Raman spectral data. PMID- 17854470 TI - Existence and characterization of allelic variants of Sao, a newly identified surface protein from Streptococcus suis. AB - Surface antigen one (Sao) is a newly identified protein from the major zoonotic pathogen, Streptococcus suis. In search of functional proteins related to the pathogenesis of Chinese S. suis 2 (SS2), unexpectedly, a variant of Sao protein was obtained. To test its prevalence in S. suis, PCR assay was adopted to address the coding genes systematically. It was found that there are three allelic variants of sao gene, namely sao-S, sao-M, and sao-L based on the different lengths of the genes (approximately 1.5, approximately 1.7, and approximately 2.0 kb, respectively). These differences were determined to be caused by heterogeneity within the number of C-terminal repeat sequences (R), which had been seen as a pathogenicity-related domain in the plant pathogen, Xanthomonas oryzae. Two variants (sao-M and sao-L) were only found in SS2. All three variant proteins were prepared in vitro and their biochemical and biophysical properties were characterized. A soluble form of Sao-M protein was then used as a capture antigen to develop an enzyme-linked immunosorbent assay method to detect antibodies against SS2 in convalescent pig sera. Taken together, the results exhibit the properties of Sao proteins and provide an efficient Sao-M-based method for monitoring SS2 infection. PMID- 17854471 TI - An anamorph of the white-rot fungus Bjerkandera adusta capable of colonizing and degrading compact disc components. AB - A Geotrichum-like fungus isolated from a biodeteriorated compact disc (CD) was able to degrade in vitro the components of different CD types. The fungal hyphae inside the CD fragments grew through the aluminium layer and produced the solubilization of this metal. Furthermore, examination of CDs by scanning electron microscopy showed that the fungus was able to destroy the pits and lands structures grooved in the polycarbonate layer, confirming degradation of this aromatic polymer. The fungus secretes aryl-alcohol oxidase and Mn2+-oxidizing peroxidase, two kinds of oxidoreductases characteristic of ligninolytic basidiomycetes. Analysis of the ITS region of ribosomal DNA, as well as the morphological characteristics, the lack of sexual forms and the profile of enzymes secreted in liquid medium identified the fungus as a Geotrichum-like anamorph of Bjerkandera adusta (Willd.) P. Karst. PMID- 17854472 TI - Invasive pneumococcal disease in Portugal prior to and after the introduction of pneumococcal heptavalent conjugate vaccine. AB - The rates of invasive pneumococcal disease (IPD), serotype distribution and antimicrobial susceptibility prior to and after the introduction of the heptavalent pneumococcal conjugate vaccine in Portuguese children were evaluated. The changes in incidence of IPD in children under 1 year old between the two periods of the study was not significant (P=0.53), despite the 21% decline. In children under 18 years old there was a 27.7% decrease in vaccine serotypes. All nonvaccine serotypes increased 71.4%. The decrease in vaccine serotypes was more impressive during the first year of life (-54.8%) than for children between 1 and 5 years of age (-19.1%). Among children under 1 year old, penicillin nonsusceptible isolates declined between the two periods of the study (47.2% vs. 25.0%) (P=0.03), as did those of cefotaxime and ceftriaxone nonsusceptible isolates. No changes were observed for isolates nonsusceptible to tetracycline and macrolides. The serotypes of these nonsusceptible isolates differed after the introduction of vaccine (P=0.01). Multiresistance increased 57.1% after the introduction of vaccine. Multiresistant isolates with vaccine serotype declined 42.9% (P<0.001), and nonvaccine serotypes appeared during the vaccination period (P<0.001). These findings suggest a replacement of vaccine serotypes by nonvaccine serotypes, mainly among nonsusceptible isolates. PMID- 17854473 TI - Serological diagnosis of syphilis: comparison of the Trep-Chek IgG enzyme immunoassay with other screening and confirmatory tests. AB - The Trep-Chek IgG Enzyme Immunoassay (Trep-Chek IgG EIA) was evaluated with 604 serum specimens submitted for syphilis serology from patients across Canada against a battery of conventional syphilis serology tests, including the Rapid Plasma Reagin (RPR) test, the Venereal Disease Research Laboratory (VDRL) test, the Treponema pallidum passive particle agglutination (TP-PA) test, the fluorescent treponemal antibody absorption (FTA-ABS) test, and the newer confirmatory test, Innogenetics INNO-LIA. On the basis of a consensus result derived from these serologic tests, 34 specimens were found to be syphilis positive (28 active and six past infections), and 570 were syphilis-negative (including 12 biological false positives). When the test results on this set of samples were compared to those obtained with the conventional tests RPR, VDRL, TP PA, and FTA-ABS, the sensitivity and specificity of the Trep-Chek IgG EIA were found to be 85.3% and 95.6%, respectively. Without further evaluation, we do not recommend use of the Trep-Chek IgG EIA as a stand-alone test for either screening or confirmatory syphilis serology. PMID- 17854474 TI - Mannose-resistant Proteus-like and P. mirabilis fimbriae have specific and additive roles in P. mirabilis urinary tract infections. AB - Proteus mirabilis is an important uropathogen that can cause complicated urinary tract infections (UTI). It produces several types of fimbriae, including mannose resistant Proteus-like (MR/P) fimbriae and P. mirabilis fimbriae (PMF). Previously, we determined that these fimbriae affect the ability of P. mirabilis to colonize the urinary tract. The objective of this study was to analyse the effect of the simultaneous lack of P. mirabilis MR/P and PMF fimbriae in UTI pathogenesis. A double mutant lacking both fimbriae was generated by allelic replacement mutagenesis. This mutant was characterized genetically and phenotypically, and tested using an in vitro uroepithelial cell adhesion assay and the ascending UTI murine model. In vitro adhesion to uroepithelial cells by the P. mirabilis pmfA/mrpA-D mutant was reduced when compared with the wild-type, although no significant differences were observed when it was compared with the single mrpA-D and pmfA mutants. However, in vivo assays showed that colonization of kidneys and bladders by the P. mirabilis pmfA/mrpA-D mutant was significantly reduced when compared with the wild-type and both single mutants. These results indicate that, although redundancy can occur, MR/P and PMF fimbriae have specific and additive roles in P. mirabilis UTI. PMID- 17854475 TI - Candida glabrata and Candida albicans; dissimilar tissue tropism and infectivity in a gnotobiotic model of mucosal candidiasis. AB - Germ-free transgenic epsilon 26 (Tgepsilon26) mice, deficient in both natural killer (NK)- and T-cells, were inoculated (orally) with each of two Candida glabrata (BG2 or BG1003) or Candida albicans (CAF2-1 or SC5314) strains. Candida glabrata- or C. albicans-colonized mice exhibited similar numbers of viable Candida in the alimentary tract. Neither C. glabrata nor C. albicans caused systemic candidiasis of endogenous (alimentary tract) origin. Candida albicans invaded oroesophageal (tongue, palate, esophagus) and keratinized gastric tissues, evoked hyperkeratosis and a prominent, chronic, granulocyte-dominated, inflammatory response in all infected tissues, stimulated the production of splenic granulocytes and was lethal for the mice within 3-5 weeks after oral colonization. The two C. glabrata strains colonized the alimentary tract and penetrated into the keratinized (cardia-antrum) gastric tissues, but in contrast to C. albicans, were unable to infect oroesophageal tissues. Furthermore, C. glabrata strains were not lethal for the Tgepsilon26 mice, and did not evoke an inflammatory response in colonized gastric tissues or stimulate the production of splenic granulocytes. This 'stealth-like' behavior could explain the ability of C. glabrata to persist in infected tissues and survive as a commensal in the alimentary tract. PMID- 17854476 TI - Characterization of Bordetella pertussis clinical isolates that do not express the tracheal colonization factor. AB - Bordetella pertussis, the causative agent of whooping cough, has remained endemic and there is a resurgence in some countries despite vaccination. Bordetella pertussis produces a wide range of virulence factors which are assumed to play an important role in infection and transmission, including tracheal colonization factor (TcfA). Here we show that clinical isolates belonging to distinct lineages may lose their ability to produce TcfA. Irreversible and reversible loss occurred, respectively, by recombination between repeats leading to deletion of the tcfA gene and by mutations in a polymorphic G-track. These phenomena may reflect adaptation to distinct niches. PMID- 17854477 TI - CpG oligodeoxynucleotides protect mice from lethal challenge with Candida albicans via a pathway involving tumor necrosis factor-alpha-dependent interleukin-12 induction. AB - In this study, we have attempted to determine whether the systemic administration of CpG oligodeoxynucleotide (CpG-ODN) 1826 would protect mice against systemic lethal Candida albicans infection. CpG-ODNs were found completely to protect mice from death and also reduced the growth of C. albicans in the kidneys. The administration of CpG-ODNs resulted in early interleukin (IL)-12 mRNA expression in the kidneys and an increase in serum IL-12 levels. The protective activity of CpG-ODN was abolished in IL-12-deficient (IL-12-/-) mice, thereby indicating the IL-12-dependency inherent to the effects of CpG-ODN. The protective effect of CpG ODN was not associated with the activity of NF-kappaB. Interestingly, in tumor necrosis factor (TNF)-alpha-deficient (TNF-/-) mice CpG-ODN neither exerted protective effects nor induced IL-12 expression. These data indicate that CpG-ODN protects animals against lethal C. albicans challenge via a pathway that involves the TNF-alpha-dependent induction of IL-12. PMID- 17854478 TI - Safety issues of Lactobacillus bulgaricus with respect to human gelatinases in vitro. AB - In oral medicine and dentistry probiotics have shown promising results in controlling dental diseases and yeast infections. This study was made to investigate the effect of eight strains of Lactobacillus bulgaricus and their effects on human matrix metalloproteinase-9 (MMP-9). The hypothesis was that these bacteria used in yoghurt production for centuries are not proteolytic and thus can be safely used in the development of probiotic preparations. Bacterial cell fractions and supernatant specimens were prepared and studied with gelatinase zymography and MMP-9 activation was assessed by immunoblotting. The effect of synthetic MMP inhibitors and a serine protease inhibitor (Pefabloc) on bacterial proteinases was studied with zymography. The results showed very low gelatinolytic activity. There was a slight difference between the supernatant and cell fractions so that the supernatant specimens produced weak gelatinolytic bands in zymography while hardly anything was seen in the cell fraction series. The tested synthetic MMP inhibitors and Pefabloc did not affect the proteolytic activity of the lactobacilli strains. The lactobacilli did not seem to induce the conversion of proMMP-9 to its active form. Consequently, our study hypothesis was confirmed and the studied Lactobacillus strains are not likely to degrade host tissue components. PMID- 17854479 TI - agr-Genotyping and transcriptional analysis of biofilm-producing Staphylococcus aureus. AB - We investigated the correlation between biofilm production and the accessory-gene regulator (agr) in 29 strains isolated from catheter-associated infections compared to a control group (30 isolates). All strains were tested for their ability to produce biofilm in a static system, and their agr genotype was determined. ScaI-restriction fragment length polymorphism for agr-typing showed that strong biofilm-producing strains belong to agr-type II. We found two new agr variants, and sequence analysis of the three PCR products revealed the insertion of IS256 within the agr-locus. Biofilm production was assessed and correlated with agr functionality, with the expression of the ica-operon and of two transcriptional regulators, sarA and rsbU. Our data show that agr-II strains produce large amounts of biofilm, possess a defective agr-system show early transcription of icaA and are defective in haemolysin activity, icaR transcription, and in the expression of the sigma(B) activator rsbU. Strains with agrIII are medium biofilm producers, have an inactive agr-system, but express icaAR and rsbU in the late- and postexponential growth phases. In agrI-IV- and IA-variants, medium or weak biofilm production was found. In these strains, the agr-locus was fully functional, rsbU-icaR and icaA were found in the late- and/or postexponential phases. Biofilm production was not affected by sarA. PMID- 17854480 TI - Interpersonal psychotherapy (IPT) for late-life depression in general practice: uptake and satisfaction by patients, therapists and physicians. AB - BACKGROUND: Interpersonal Psychotherapy (IPT) is recommended in most depression treatment guidelines and proved to be a suitable treatment for elderly depressed patients. Despite the favorable results of IPT in research populations, the dissemination to general practice is surprisingly limited. Little is known about uptake and satisfaction when this therapy is introduced into real-life general practice. METHODS: Motivation and evaluation of patients, GPs and therapists were recorded and organizational barriers described alongside a randomized controlled trial. IPT, given by mental health workers, was compared with usual general practitioner (GP) care. Included were patients (> or =55 years) who met the DSM IV criteria for major depressive disorder. RESULTS: Patients were motivated for the psychotherapy intervention: of the 205 eligible patients, 143 (70%) entered the study, and of the 69 patients who were offered IPT, 77% complied with the treatment. IPT proved to be an attractive therapy for patients as well as for therapists from mental health organizations. General practitioners evaluated the intervention positively afterwards, mainly because of the time-limited and structured approach. Organizational barriers: no IPT therapists were available; an IPT trainer and supervisor had to be trained and training materials had to be developed and translated. Additionally, there was a lack of office space in some general practices; for therapists from private practices it was not feasible to participate because of financial reasons. IPT was superior to usual care in patients with moderate to severe depression. CONCLUSION: As we succeeded in delivering IPT in primary care practice, and as IPT was superior to usual care, there are grounds to support the implementation of IPT for depressed elderly patients within general practice, as long as the practices have room for the therapists and financial barriers can be overcome. Consolidation may be achieved by making this intervention available through practice nurses or community psychiatric nurses who deliver IPT as part of a more comprehensive depression management program. PMID- 17854481 TI - Ambient biomass smoke and cardio-respiratory hospital admissions in Darwin, Australia. AB - BACKGROUND: Increasing severe vegetation fires worldwide has been attributed to both global environmental change and land management practices. However there is little evidence concerning the population health effects of outdoor air pollution derived from biomass fires. Frequent seasonal bushfires near Darwin, Australia provide an opportunity to examine this issue. We examined the relationship between atmospheric particle loadings <10 microns in diameter (PM10), and emergency hospital admissions for cardio-respiratory conditions over the three fire seasons of 2000, 2004 and 2005. In addition we examined the differential impacts on Indigenous Australians, a high risk population subgroup. METHODS: We conducted a case-crossover analysis of emergency hospital admissions with principal ICD10 diagnosis codes J00-J99 and I00-I99. Conditional logistic regression models were used to calculate odds ratios for admission with 10 microg/m3 rises in PM10. These were adjusted for weekly influenza rates, same day mean temperature and humidity, the mean temperature and humidity of the previous three days, days with rainfall > 5 mm, public holidays and holiday periods. RESULTS: PM10 ranged from 6.4 - 70.0 microg/m3 (mean 19.1). 2466 admissions were examined of which 23% were for Indigenous people. There was a positive relationship between PM10 and admissions for all respiratory conditions (OR 1.08 95%CI 0.98-1.18) with a larger magnitude in the Indigenous subpopulation (OR1.17 95% CI 0.98-1.40). While there was no relationship between PM10 and cardiovascular admissions overall, there was a positive association with ischaemic heart disease in Indigenous people, greatest at a lag of 3 days (OR 1.71 95%CI 1.14-2.55). CONCLUSION: PM10 derived from vegetation fires was predominantly associated with respiratory rather than cardiovascular admissions. This outcome is consistent with the few available studies of ambient biomass smoke pollution. Indigenous people appear to be at higher risk of cardio respiratory hospital admissions associated with exposure to PM10. PMID- 17854482 TI - Recent evolution of alternative reproductive modes in the 'living fossil' Triops cancriformis. AB - BACKGROUND: The Notostraca is a small but ancient crustacean order with a contrasting combination of a conservative morphology and a wide range of reproductive modes. The tadpole shrimp Triops cancriformis, includes bisexual - the putatively ancestral state -, androdioecious and hermaphrodite populations. As hermaphroditism and androdioecy confer a colonisation advantage, we expect the postglacial colonisation of northern Europe to have been effected by lineages with such reproductive modes. Therefore, N European populations should be composed of closely related lineages reflecting a recent range expansion. In contrast, glacial refugia in the south should contain bisexual populations with high haplotype diversity and more population structuring. To test these hypotheses, we analysed the geographic distribution of reproductive modes based on new and published sex ratio data. In addition, we investigated the European phylogeography of T. cancriformis by sequencing over a 1000 bp of mitochondrial DNA (mtDNA) in individuals from a large sample of populations of the three recognised subspecies. RESULTS: Bisexual populations were only found in the Iberian Peninsula, with the rest of European populations showing low male proportions or no males. Androdioecious populations were found in Central and Eastern Europe. Regarding mtDNA diversity, Spanish and Moroccan populations of T. c. mauritanicus were highly divergent, and showed strong population structure. In contrast, Triops c. cancriformis and T. c. simplex formed a single mtDNA lineage with low haplotype diversity. This diversity was structured into two phylogenetic clades (A, B), coexisting in E Germany. Basal haplotypes of both lineages were found in the Iberian Peninsula. Most of the populations in clade A and B are either hermaphroditic or androdioecious, with the only bisexual population in these clades found in the Iberian Peninsula. The genetic divergence between these two clades suggests a split in the Late Pleistocene and their geographic distribution reflects a complex evolutionary history of European Triops populations, with possibly two episodes of range expansions - one of them by clade A - involving androdioecious and hermaphroditic populations. CONCLUSION: As we predicted, N European populations of T. cancriformis are closely related, with few widely distributed haplotypes and indications of a recent range expansion involving hermaphroditic/androdioecious lineages. A possible second range expansion or long distance colonisation may have created the secondary contact zone between T. c. cancriformis/simplex clades A and B. The large haplotype diversity and strong genetic subdivision in the Iberian Peninsula, which is known to contain only bisexual populations, strongly suggest that this area was a Pleistocene refugium for T. cancriformis, although the occurrence of additional eastern refugia cannot be ruled out. Our data support the status of T. c. mauritanicus as a separate species and the colonisation of N Africa from the Iberian Peninsula. We suggest that hermaphroditism/androdioecy has evolved recently in T. cancriformis and has facilitated the postglacial colonisation of northern Europe. PMID- 17854483 TI - Social regulation of gene expression in human leukocytes. AB - BACKGROUND: Social environmental influences on human health are well established in the epidemiology literature, but their functional genomic mechanisms are unclear. The present study analyzed genome-wide transcriptional activity in people who chronically experienced high versus low levels of subjective social isolation (loneliness) to assess alterations in the activity of transcription control pathways that might contribute to increased adverse health outcomes in social isolates. RESULTS: DNA microarray analysis identified 209 genes that were differentially expressed in circulating leukocytes from 14 high- versus low lonely individuals, including up-regulation of genes involved in immune activation, transcription control, and cell proliferation, and down-regulation of genes supporting mature B lymphocyte function and type I interferon response. Promoter-based bioinformatic analyses showed under-expression of genes bearing anti-inflammatory glucocorticoid response elements (GREs; p = 0.032) and over expression of genes bearing response elements for pro-inflammatory NF-kappaB/Rel transcription factors (p = 0.011). This reciprocal shift in pro- and anti inflammatory signaling was not attributable to differences in circulating cortisol levels, or to other demographic, psychological, or medical characteristics. Additional transcription control pathways showing differential activity in bioinformatic analyses included the CREB/ATF, JAK/STAT, IRF1, C/EBP, Oct, and GATA pathways. CONCLUSION: These data provide the first indication that human genome-wide transcriptional activity is altered in association with a social epidemiological risk factor. Impaired transcription of glucocorticoid response genes and increased activity of pro-inflammatory transcription control pathways provide a functional genomic explanation for elevated risk of inflammatory disease in individuals who experience chronically high levels of subjective social isolation. PMID- 17854484 TI - The sociodemographic patterning of drinking and binge drinking in Estonia, Latvia, Lithuania and Finland, 1994-2002. AB - BACKGROUND: Despite the relatively low recorded alcohol consumption level, the Baltic countries (Estonia, Latvia and Lithuania) and neighbouring Finland suffer from similar harmful consequences related to the use of alcoholic beverages, including socio-economic inequalities in alcohol related mortality. Comparative evidence is needed to understand harmful drinking patterns and to implement preventive alcohol policies also in the Baltic countries. This study compared heavy and binge drinking by sex, age, education, urbanisation and marital status in the Baltic countries and Finland. The data were nationally representative postal surveys conducted in Estonia (n = 6271), Latvia (n = 6106), Lithuania (n = 7966) and Finland (n = 15764) during 1994-2002. The criterion for heavy drinking was at least 15 portions weekly among men, and at least five among women, and for binge drinking at least six portions per one occasion. Heavy drinking was more common among younger participants in all countries, and in Latvia among the less educated. Among Finnish men, and among women from all countries except Latvia, the better-educated were more often heavy drinkers. In Latvia and Finland, urban men, and in all countries, urban women, were more often heavy drinkers. Heavy drinking was more common among non-married Lithuanian and Finnish men, and Finnish women. Binge drinking was more common among less-educated Estonian and Latvian men, and among younger and less-educated women in all countries. Our results support the continued power of traditional drinking habits in the North Eastern part of Europe. In the future the target groups for prevention of excessive drinking should also include young and less-educated women in all four countries studied. PMID- 17854485 TI - DNA evidence for global dispersal and probable endemicity of protozoa. AB - BACKGROUND: It is much debated whether microbes are easily dispersed globally or whether they, like many macro-organisms, have historical biogeographies. The ubiquitous dispersal hypothesis states that microbes are so numerous and so easily dispersed worldwide that all should be globally distributed and found wherever growing conditions suit them. This has been broadly upheld for protists (microbial eukaryotes) by most morphological and some molecular analyses. However, morphology and most previously used evolutionary markers evolve too slowly to test this important hypothesis adequately. RESULTS: Here we use a fast evolving marker (ITS1 rDNA) to map global diversity and distribution of three different clades of cercomonad Protozoa (Eocercomonas and Paracercomonas: phylum Cercozoa) by sequencing multiple environmental gene libraries constructed from 47 80 globally-dispersed samples per group. Even with this enhanced resolution, identical ITS sequences (ITS-types) were retrieved from widely separated sites and on all continents for several genotypes, implying relatively rapid global dispersal. Some identical ITS-types were even recovered from both marine and non marine samples, habitats that generally harbour significantly different protist communities. Conversely, other ITS-types had either patchy or restricted distributions. CONCLUSION: Our results strongly suggest that geographic dispersal in macro-organisms and microbes is not fundamentally different: some taxa show restricted and/or patchy distributions while others are clearly cosmopolitan. These results are concordant with the 'moderate endemicity model' of microbial biogeography. Rare or continentally endemic microbes may be ecologically significant and potentially of conservational concern. We also demonstrate that strains with identical 18S but different ITS1 rDNA sequences can differ significantly in terms of morphological and important physiological characteristics, providing strong additional support for global protist biodiversity being significantly higher than previously thought. PMID- 17854486 TI - Passage and reversal effects on gene expression of bovine meniscal fibrochondrocytes. AB - The knee meniscus contains a mixed population of cells that exhibit fibroblastic as well as chondrocytic characteristics. Tissue engineering studies and future therapies for the meniscus require a large population of cells that are seeded on scaffolds. To achieve this, monolayer expansion is often used as a technique to increase cell number. However, the phenotype of these cells may be significantly different from that of the primary population. The objective of this study was to investigate changes in meniscal fibrochondrocytes at the gene expression level over four passages using quantitative real-time reverse transcriptase polymerase chain reaction. Cells from the inner two-thirds of bovine medial menisci were used. Four extracellular matrix (ECM) molecules, commonly found in the meniscus, were investigated, namely collagen I, collagen II, aggrecan and cartilage oligomeric matrix protein (COMP). In addition, primary and passaged meniscus fibrochondrocytes were placed on surfaces coated with collagen I or aggrecan protein to investigate whether any gene expression changes resulting from passage could be reversed. Collagen I expression was found to increase with the number of passages, whereas collagen II and COMP expression decreased. Collagen I and aggrecan surface coatings were shown to downregulate and upregulate collagen I and COMP expression levels, respectively, in passaged cells. However, decreases in collagen II expression could not be reversed by either protein coating. These results indicate that although monolayer expansion results in significant changes in gene expression in meniscal fibrochondrocytes, protein coatings may be used to regain the primary cell expression of several ECM molecules. PMID- 17854487 TI - Interactions between the adducin 2 gene and antihypertensive drug therapies in determining blood pressure in people with hypertension. AB - BACKGROUND: As part of the NHLBI Family Blood Pressure Program, the Genetic Epidemiology Network of Arteriopathy (GENOA) recruited 575 sibships (n = 1583 individuals) from Rochester, MN who had at least two hypertensive siblings diagnosed before age 60. Linkage analysis identified a region on chromosome 2 that was investigated using 70 single nucleotide polymorphisms (SNPs) typed in 7 positional candidate genes, including adducin 2 (ADD2). METHOD: To investigate whether blood pressure (BP) levels in these hypertensives (n = 1133) were influenced by gene-by-drug interactions, we used cross-validation statistical methods (i.e., estimating a model for predicting BP levels in one subgroup and testing it in a different subgroup). These methods greatly reduced the chance of false positive findings. RESULTS: Eight SNPs in ADD2 were significantly associated with systolic BP in untreated hypertensives (p-value < 0.05). Moreover, we also identified SNPs associated with gene-by-drug interactions on systolic BP in drug-treated hypertensives. The TT genotype at SNP rs1541582 was associated with an average systolic BP of 133 mmHg in the beta-blocker subgroup and 148 mmHg in the diuretic subgroup after adjusting for overall mean differences among drug classes. CONCLUSION: Our findings suggest that hypertension candidate gene variation may influence BP responses to specific antihypertensive drug therapies and measurement of genetic variation may assist in identifying subgroups of hypertensive patients who will benefit most from particular antihypertensive drug therapies. PMID- 17854488 TI - The necessary shift from diagnostic to prognostic research. AB - BACKGROUND: Do doctors really need to establish an etiological diagnosis each time a patient presents? Or might it often be more effective to treat simply on the basis of symptoms and signs alone, relying on research and on our experience of outcomes for patients who presented in similar ways in the past? DISCUSSION: At a time of increase health care costs especially in pharmaceuticals and expensive diagnostic tests, this article uses examples from recent research to address this question. Our examples come from general practice, because that is where doctors frequently see patients presenting with a yet undifferentiated disease which is consequently difficult to diagnose. The examples include respiratory tract infections, low back pain and shoulder pain. Finally we discuss the 'something is wrong' feeling. SUMMARY: We conclude that, in addition to diagnostic research, a renewed focus on prognostic research is needed. PMID- 17854489 TI - PathFinder: mining signal transduction pathway segments from protein-protein interaction networks. AB - BACKGROUND: A Signal transduction pathway is the chain of processes by which a cell converts an extracellular signal into a response. In most unicellular organisms, the number of signal transduction pathways influences the number of ways the cell can react and respond to the environment. Discovering signal transduction pathways is an arduous problem, even with the use of systematic genomic, proteomic and metabolomic technologies. These techniques lead to an enormous amount of data and how to interpret and process this data becomes a challenging computational problem. RESULTS: In this study we present a new framework for identifying signaling pathways in protein-protein interaction networks. Our goal is to find biologically significant pathway segments in a given interaction network. Currently, protein-protein interaction data has excessive amount of noise, e.g., false positive and false negative interactions. First, we eliminate false positives in the protein-protein interaction network by integrating the network with microarray expression profiles, protein subcellular localization and sequence information. In addition, protein families are used to repair false negative interactions. Then the characteristics of known signal transduction pathways and their functional annotations are extracted in the form of association rules. CONCLUSION: Given a pair of starting and ending proteins, our methodology returns candidate pathway segments between these two proteins with possible missing links (recovered false negatives). In our study, S. cerevisiae (yeast) data is used to demonstrate the effectiveness of our method. PMID- 17854490 TI - Intensity Modulated Radiotherapy (IMRT) and Fractionated Stereotactic Radiotherapy (FSRT) for children with head-and-neck-rhabdomyosarcoma. AB - BACKGROUND: The present study evaluates the outcome of 19 children with rhabdomyosarcoma of the head-and-neck region treated with Intensity Modulated Radiotherapy (IMRT) or Fractionated Stereotactic Radiotherapy (FSRT) between August 1995 and November 2005. METHODS: We treated 19 children with head-and-neck rhabdomyosarcoma with FSRT (n = 14) or IMRT (n = 5) as a part of multimodal therapy. Median age at the time of radiation therapy was 5 years (range 2-15 years). All children received systemic chemotherapy according to the German Soft Tissue Sarcoma Study protocols. Median size of treatment volume for RT was 93,4 ml. We applied a median total dose of 45 Gy (range 32 Gy - 54 Gy) using a median fractionation of 5 x 1,8 Gy/week (range 1,6 Gy - 1,8 Gy). The median time interval between primary diagnosis and radiation therapy was 5 months (range 3-9 months). RESULTS: After RT, the 3- and 5-year survival rate was 94%. The 3- and 5 year actuarial local control rate after RT was 89%. The actuarial freedom of distant metastases rate at 3- and 5-years was 89% for all patients. Radiotherapy was well tolerated in all children and could be completed without interruptions > 4 days. No toxicities >CTC grade 2 were observed. The median follow-up time after RT was 17 months. CONCLUSION: IMRT and FSRT lead to excellent outcome in children with head-and-neck RMS with a low incidence of treatment-related side effects. PMID- 17854491 TI - Molecular characterization and temporal expression profiling of presenilins in the developing porcine brain. AB - BACKGROUND: The transmembrane presenilin (PSEN) proteins, PSEN1 and PSEN2, have been proposed to be the catalytic components of the gamma-secretase protein complex, which is an intramembranous multimeric protease involved in development, cell regulatory processes, and neurodegeneration in Alzheimer's disease. Here we describe the sequencing, chromosomal mapping, and polymorphism analysis of PSEN1 and PSEN2 in the domestic pig (Sus scrofa domesticus). RESULTS: The porcine presenilin proteins showed a high degree of homology over their entire sequences to the PSENs from mouse, bovine, and human. PSEN1 and PSEN2 transcription was examined during prenatal development of the brain stem, hippocampus, cortex, basal ganglia, and cerebellum at embryonic days 60, 80, 100, and 114, which revealed distinct temporal- and tissue-specific expression profiles. Furthermore, immunohistochemical analysis of PSEN1 and PSEN2 showed similar localization of the proteins predominantly in neuronal cells in all examined brain areas. CONCLUSION: The data provide evidence for structural and functional conservation of PSENs in mammalian lineages, and may suggest that the high sequence similarity and colocalization of PSEN1 and PSEN2 in brain tissue reflect a certain degree of functional redundancy. The data show that pigs may provide a new animal model for detailed analysis of the developmental functions of the PSENs. PMID- 17854492 TI - Phylogeography of the Solanaceae-infecting Basidiomycota fungus Rhizoctonia solani AG-3 based on sequence analysis of two nuclear DNA loci. AB - BACKGROUND: The soil fungus Rhizoctonia solani anastomosis group 3 (AG-3) is an important pathogen of cultivated plants in the family Solanaceae. Isolates of R. solani AG-3 are taxonomically related based on the composition of cellular fatty acids, phylogenetic analysis of nuclear ribosomal DNA (rDNA) and beta-tubulin gene sequences, and somatic hyphal interactions. Despite the close genetic relationship among isolates of R. solani AG-3, field populations from potato and tobacco exhibit comparative differences in their disease biology, dispersal ecology, host specialization, genetic diversity and population structure. However, little information is available on how field populations of R. solani AG 3 on potato and tobacco are shaped by population genetic processes. In this study, two field populations of R. solani AG-3 from potato in North Carolina (NC) and the Northern USA; and two field populations from tobacco in NC and Southern Brazil were examined using sequence analysis of two cloned regions of nuclear DNA (pP42F and pP89). RESULTS: Populations of R. solani AG-3 from potato were genetically diverse with a high frequency of heterozygosity, while limited or no genetic diversity was observed within the highly homozygous tobacco populations from NC and Brazil. Except for one isolate (TBR24), all NC and Brazilian isolates from tobacco shared the same alleles. No alleles were shared between potato and tobacco populations of R. solani AG-3, indicating no gene flow between them. To infer historical events that influenced current geographical patterns observed for populations of R. solani AG-3 from potato, we performed an analysis of molecular variance (AMOVA) and a nested clade analysis (NCA). Population differentiation was detected for locus pP89 (Phi ST = 0.257, significant at P < 0.05) but not for locus pP42F (Phi ST = 0.034, not significant). Results based on NCA of the pP89 locus suggest that historical restricted gene flow is a plausible explanation for the geographical association of clades. Coalescent-based simulations of genealogical relationships between populations of R. solani AG-3 from potato and tobacco were used to estimate the amount and directionality of historical migration patterns in time, and the ages of mutations of populations. Low rates of historical movement of genes were observed between the potato and tobacco populations of R. solani AG-3. CONCLUSION: The two sisters populations of the basidiomycete fungus R. solani AG-3 from potato and tobacco represent two genetically distinct and historically divergent lineages that have probably evolved within the range of their particular related Solanaceae hosts as sympatric species. PMID- 17854493 TI - Analysis of global control of Escherichia coli carbohydrate uptake. AB - BACKGROUND: Global control influences the regulation of many individual subsystems by superimposed regulator proteins. A prominent example is the control of carbohydrate uptake systems by the transcription factor Crp in Escherichia coli. A detailed understanding of the coordination of the control of individual transporters offers possibilities to explore the potential of microorganisms e.g. in biotechnology. RESULTS: An o.d.e. based mathematical model is presented that maps a physiological parameter - the specific growth rate - to the sensor of the signal transduction unit, here a component of the bacterial phosphotransferase system (PTS), namely EIIACrr. The model describes the relation between the growth rate and the degree of phosphorylation of EIIA crr for a number of carbohydrates by a distinctive response curve, that differentiates between PTS transported carbohydrates and non-PTS carbohydrates. With only a small number of kinetic parameters, the model is able to describe a broad range of experimental steady state and dynamical conditions. CONCLUSION: The steady-state characteristic presented shows a relationship between the growth rate and the output of the sensor system PTS. The glycolytic flux that is measured by this sensor is a good indicator to represent the nutritional status of the cell. PMID- 17854494 TI - Reduced modeling of signal transduction - a modular approach. AB - BACKGROUND: Combinatorial complexity is a challenging problem in detailed and mechanistic mathematical modeling of signal transduction. This subject has been discussed intensively and a lot of progress has been made within the last few years. A software tool (BioNetGen) was developed which allows an automatic rule based set-up of mechanistic model equations. In many cases these models can be reduced by an exact domain-oriented lumping technique. However, the resulting models can still consist of a very large number of differential equations. RESULTS: We introduce a new reduction technique, which allows building modularized and highly reduced models. Compared to existing approaches further reduction of signal transduction networks is possible. The method also provides a new modularization criterion, which allows to dissect the model into smaller modules that are called layers and can be modeled independently. Hallmarks of the approach are conservation relations within each layer and connection of layers by signal flows instead of mass flows. The reduced model can be formulated directly without previous generation of detailed model equations. It can be understood and interpreted intuitively, as model variables are macroscopic quantities that are converted by rates following simple kinetics. The proposed technique is applicable without using complex mathematical tools and even without detailed knowledge of the mathematical background. However, we provide a detailed mathematical analysis to show performance and limitations of the method. For physiologically relevant parameter domains the transient as well as the stationary errors caused by the reduction are negligible. CONCLUSION: The new layer based reduced modeling method allows building modularized and strongly reduced models of signal transduction networks. Reduced model equations can be directly formulated and are intuitively interpretable. Additionally, the method provides very good approximations especially for macroscopic variables. It can be combined with existing reduction methods without any difficulties. PMID- 17854495 TI - A comparison of patients' perceptions and an audit of health promotion practice within a UK hospital. AB - BACKGROUND: UK hospitals are required to monitor the health promotion services they provide for patients. We compared the use of audit and patient questionnaires as appropriate tools for monitoring whether patients are screened for modifiable risk factors (smoking, alcohol use, obesity, diet, and physical activity), whether staff correctly identify risk factor presence and deliver health promotion when a risk factor is identified. METHODS: We sent a questionnaire post-discharge to 322 hospitalised adult patients discharged alive between January and March 2006, and audited their hospital case notes for evidence of screening for risk factors, identification of risk factors, and delivery of health promotion to change risk factors. Agreement between the audit and questionnaire findings was assessed by Kappa statistic. RESULTS: There was little relationship between what was written in the case notes and what patients thought had happened. Agreement between the audit and questionnaire for screening of risk factors was at best fair. For the delivery of health promotion agreement was moderate for alcohol, poor for exercise, and no different from chance for smoking and diet. Agreement on identifying risk factors was very good for obesity, good for smoking, and moderate for alcohol misuse. The identification of diet quality and level of physical activity was too low in the audit to allow statistical comparison with self-reported diet and activity. CONCLUSION: A direct comparison of data gathered in the audit and patient questionnaires provides a comprehensive picture of health promotion practice within hospitals. Poor screening agreement is likely to be due to errors in patients' recall of screening activities. Audit is therefore the preferred method for evaluating screening of risk factors, but further insight into screening practice can be gained by using the questionnaire in conjunction with audit. If a patient does not recognise that they received health promotion, then this is tantamount to not receiving it, we therefore recommend that the patient questionnaire is the preferred method for monitoring health promotion delivered. For monitoring the accuracy of risk factor identification either method is appropriate as long as the hospital uses validated screening tools for identifying alcohol misuse, diet, and physical activity. PMID- 17854496 TI - Pharmacokinetics and pharmacodynamics of danaparoid during continuous venovenous hemofiltration: a pilot study. AB - BACKGROUND: In patients with suspected heparin-induced thrombocytopenia (HIT) who need renal replacement therapy, a nonheparin anticoagulant has to be chosen to prevent thrombosis in the extracorporeal circuit. Danaparoid, a low-molecular weight heparinoid consisting of heparan sulphate, dermatan sulphate, and chondroitin sulphate, is recommended for systemic anticoagulation in patients with HIT. However, there are few data on the use of danaparoid in patients with acute renal failure, especially in patients dependent on renal replacement therapy such as continuous venovenous hemofiltration (CVVH). In the present study, we analyzed the pharmacokinetics and pharmacodynamics of danaparoid during CVVH in patients with suspected HIT. METHODS: Based on a mathematical model, a dosing scheme for danaparoid was designed, aiming at anti-Xa levels of 0.5 to 0.7 U/mL, with a maximum of 1.0 U/mL. This dosing scheme was prospectively tested in the first CVVH run of a cohort of five patients with suspected HIT. CVVH with a blood flow rate of 150 mL/minute and a substitution rate of 2,000 mL/hour was performed with a cellulose triacetate membrane. Danaparoid was administered as a continuous infusion of 100 anti-Xa-U/hour after a loading dose of 3,500 anti-Xa U. Serial measurements of anti-Xa activity and prothrombin fragment F1+2 were performed at baseline, at t = 5, 15, and 30 minutes, and at t = 1, 2, 4, 8, 16, and 24 hours after the danaparoid loading dose. RESULTS: The median anti-Xa activity reached a maximum of 1.02 (0.66 to 1.31) anti-Xa-U/mL after 15 minutes and gradually declined to 0.40 (0.15 to 0.58) anti-Xa-U/mL over the span of 24 hours. Target anti-Xa levels were reached from 2 to 12 hours after the loading dose. Median prothrombin fragment F1+2 gradually decreased from 432 (200 to 768) to 262 (248 to 317) pmol/L after 24 hours. No bleeding or thromboembolic events occurred throughout the described treatment period. CONCLUSION: Danaparoid administered by a continuous infusion of 100 anti-Xa-U/hour after a loading dose of 3,500 anti-Xa-U elicited target anti-Xa levels from 2 to 12 hours after the loading dose, without bleeding or thromboembolic events during the described CVVH treatment in patients with suspected HIT. PMID- 17854497 TI - Protracted outbreak of S. Enteritidis PT 21c in a large Hamburg nursing home. AB - BACKGROUND: During August 2006, a protracted outbreak of Salmonella (S.) Enteritidis infections in a large Hamburg nursing home was investigated. METHODS: A site visit of the home was conducted and food suppliers' premises tested for Salmonella. Among nursing home residents a cohort study was carried out focusing on foods consumed in the three days before the first part of the outbreak. Instead of relying on residents' memory, data from the home's patient food ordering system was used as exposure data. S. Enteritidis isolates from patients and suspected food vehicles were phage typed and compared. RESULTS: Within a population of 822 nursing home residents, 94 case patients among residents (1 fatality) and 17 among staff members were counted 6 through 29 August. The outbreak peaked 7 through 9 August, two days after a spell of very warm summer weather. S. Enteritidis was consistently recovered from patients' stools throughout the outbreak. Among the food items served during 5 through 7 August, the cohort study pointed to afternoon cake on all three days as potential risk factors for disease. Investigation of the bakery supplying the cake yielded S. Enteritidis from cakes sampled 31 August. Comparison of the isolates by phage typing demonstrated both isolates from patients and the cake to be the exceedingly rare phage type 21c. CONCLUSION: Cake (various types served on various days) contaminated with S. Enteritidis were the likely vehicle of the outbreak in the nursing home. While the cakes were probably contaminated with low pathogen dose throughout the outbreak period, high ambient summer temperatures and failure to keep the cake refrigerated led to high pathogen dose in cake on some days and in some of the housing units. This would explain the initial peak of cases, but also the drawn out nature of the outbreak with cases until the end of August. Suggestions are made to nursing homes, aiding in outbreak prevention. Early outbreak detection is crucial, such that counter measures can be swift and drawn-out outbreaks of nosocomial food-borne infections avoided. PMID- 17854498 TI - BP1 transcriptionally activates bcl-2 and inhibits TNFalpha-induced cell death in MCF7 breast cancer cells. AB - INTRODUCTION: We have previously shown that the Beta Protein 1 (BP1) homeodomain protein is expressed in 81% of invasive ductal breast carcinomas, and that increased BP1 expression correlates with tumor progression. The purpose of our current investigation was to determine whether elevated levels of BP1 in breast cancer cells are associated with increased cell survival. METHODS: Effects on cell viability and apoptosis of MCF7 cells stably overexpressing BP1 were determined using MTT and Annexin V assays, and through examination of caspase activation. TNFalpha was used to induce apoptosis. The potential regulation of apoptosis-associated genes by BP1 was studied using real-time PCR and western blot analyses. Electrophoretic mobility shift assays, site-directed mutagenesis, and transient assays were performed to specifically characterize the interaction of BP1 with the promoter of the bcl-2 gene. RESULTS: Stable overexpression of BP1 led to inhibition of apoptosis in MCF7 breast cancer cells challenged with TNFalpha. Increased BP1 resulted in reduced processing and activation of caspase 7, caspase-8, and caspase-9, and inactivation of the caspase substrate Poly(ADP Ribose) Polymerase (PARP). Increased levels of full-length PARP and a decrease in procaspase-8 were also associated with BP1 overexpression. The bcl-2 gene is a direct target of BP1 since: (i) BP1 protein bound to a consensus binding sequence upstream of the bcl-2 P1 promoter in vitro. (ii) MCF7 cells overexpressing BP1 showed increased levels of bcl-2 mRNA and protein. (iii) Transient assays indicated that increased bcl-2 promoter activity is due to direct binding and modulation by BP1 protein. BP1 expression also prevented TNFalpha-mediated downregulation of bcl-2 mRNA and protein. CONCLUSION: These findings suggest mechanisms by which increased BP1 may impart a survival advantage to breast cancer cells, which could lead to increased resistance to therapeutic agents in patients. PMID- 17854499 TI - The role of surgical audit in improving patient management; nasal haemorrhage: an audit study. AB - BACKGROUND: Nasal bleeding remains one of the most common Head & Neck Surgical (Ear Nose and Throat [ENT]/Oral & Maxillofacial Surgery [OMFS]) emergencies resulting in hospital admission. In the majority of cases, no other intervention is required other than nasal packing, and it was felt many cases could ideally be managed at home, without further medical interference. A limited but national telephone survey of accident and emergency departments revealed that early discharge practice was identified in some rural areas and urban departments (where adverse socio-demographic factors resulted in poor patient compliance to admission or follow up), with little adverse patient sequelae. A simple nasal packing protocol was also identified. The aim of this audit was to determine if routine nasal haemorrhage (epistaxis) can be managed at home with simple nasal packing; a retrospective and prospective audit. Ethical committee approval was obtained. Similar practice was identified in other UK accident and emergency centres. Literature was reviewed and best practice identified. Regional consultation and feedback with regard to prospective changes and local applicability of areas of improved practice mutually agreed upon with involved providers of care. METHODS: Retrospective: The Epistaxis admissions for the previous four years during the same seven months (September to March). Prospective: 60 consecutive patients referred with a diagnosis of Nasal bleeding over a seven month time course (September to March). All patients were over 16, not pregnant and gave fully informed counselled consent. New Guidelines for the management of nosebleeds, nasal packing protocols (with Netcel) and discharge policy were developed at the Hospital. Training of accident and emergency and emergency ENT staff was provided together with access to adequate examination and treatment resources. Detailed patient information leaflets were piloted and developed for use. RESULTS: Previously all patients requiring nasal packing were admitted. The type of nasal packing included Gauge impregnated Bismuth Iodoform Paraffin Paste, Nasal Tampon, and Vaseline gauge. Over the previous four year period (September to March) a mean of 28 patients were admitted per month, with a mean duration of in patient stay of 2.67 days. In the prospective audit the total number of admissions was significantly reduced, by over 70%, (chi2 = 25.05, df = 6, P < 0.0001), despite no significant change in the number of monthly epistaxis referrals (chi2 = 4.99, df = 6, P < 0.0001). There was also a significant increase in the mean age of admitted patients with epistaxis (chi2 = 22.71, df = 5, P < 0.0001), the admitted patients had a mean length of stay of 2.53 days. This policy results is an estimated saved 201.39 bed days per annum resulting in an estimated annual speciality saving of over pound 50,000, allowing resource re allocation to other areas of need. Furthermore, bed usage could be optimised for other emergency or elective work. CONCLUSION: Exclusion criteria have now been expanded to exclude traumatic nasal haemorrhage. New adjunctive therapies now include direct endoscopic bipolar diathermy of bleeding points, and the judicious use of topical pro-coagulant agents applied via the nasal tampon. Expansion of the audit protocols for use in general practice.This original audit informed clinical practice and had potential benefits for patients, clinicians, and provision of service. Systematic replication of this project, possibly on a regional and general practice basis, could result in further financial savings, which would allow development of improved patient services and delivery of care. PMID- 17854500 TI - Molecular evolution of type VI intermediate filament proteins. AB - BACKGROUND: Tanabin, transitin and nestin are type VI intermediate filament (IF) proteins that are developmentally regulated in frogs, birds and mammals, respectively. Tanabin is expressed in the growth cones of embryonic vertebrate neurons, whereas transitin and nestin are found in myogenic and neurogenic cells. Another type VI IF protein, synemin, is expressed in undifferentiated and mature muscle cells of birds and mammals. In addition to an IF-typical alpha-helical core domain, type VI IF proteins are characterized by a long C-terminal tail often containing distinct repeated motifs. The molecular evolution of type VI IF proteins remains poorly studied. RESULTS: To examine the evolutionary history of type VI IF proteins, sequence comparisons, BLAST searches, synteny studies and phylogenic analyses were performed. This study provides new evidence that tanabin, transitin and nestin are indeed orthologous type VI IF proteins. It demonstrates that tanabin, transitin and nestin genes share intron positions and sequence identities, have a similar chromosomal context and display closely related positions in phylogenic analyses. Despite this homology, fast evolution rates of their C-terminal extremity have caused the appearance of repeated motifs with distinct biological activities. In particular, our in silico and in vitro analyses of their tail domain have shown that (avian) transitin, but not (mammalian) nestin, contains a repeat domain displaying nucleotide hydrolysis activity. CONCLUSION: These analyses of the evolutionary history of the IF proteins fit with a model in which type VI IFs form a branch distinct from NF proteins and are composed of two major proteins: synemin and nestin orthologs. Rapid evolution of the C-terminal extremity of nestin orthologs could be responsible for their divergent functions. PMID- 17854501 TI - Support Vector Machine-based method for predicting subcellular localization of mycobacterial proteins using evolutionary information and motifs. AB - BACKGROUND: In past number of methods have been developed for predicting subcellular location of eukaryotic, prokaryotic (Gram-negative and Gram-positive bacteria) and human proteins but no method has been developed for mycobacterial proteins which may represent repertoire of potent immunogens of this dreaded pathogen. In this study, attempt has been made to develop method for predicting subcellular location of mycobacterial proteins. RESULTS: The models were trained and tested on 852 mycobacterial proteins and evaluated using five-fold cross validation technique. First SVM (Support Vector Machine) model was developed using amino acid composition and overall accuracy of 82.51% was achieved with average accuracy (mean of class-wise accuracy) of 68.47%. In order to utilize evolutionary information, a SVM model was developed using PSSM (Position-Specific Scoring Matrix) profiles obtained from PSI-BLAST (Position-Specific Iterated BLAST) and overall accuracy achieved was of 86.62% with average accuracy of 73.71%. In addition, HMM (Hidden Markov Model), MEME/MAST (Multiple Em for Motif Elicitation/Motif Alignment and Search Tool) and hybrid model that combined two or more models were also developed. We achieved maximum overall accuracy of 86.8% with average accuracy of 89.00% using combination of PSSM based SVM model and MEME/MAST. Performance of our method was compared with that of the existing methods developed for predicting subcellular locations of Gram-positive bacterial proteins. CONCLUSION: A highly accurate method has been developed for predicting subcellular location of mycobacterial proteins. This method also predicts very important class of proteins that is membrane-attached proteins. This method will be useful in annotating newly sequenced or hypothetical mycobacterial proteins. Based on above study, a freely accessible web server TBpred http://www.imtech.res.in/raghava/tbpred/ has been developed. PMID- 17854502 TI - Corpus refactoring: a feasibility study. AB - BACKGROUND: Most biomedical corpora have not been used outside of the lab that created them, despite the fact that the availability of the gold-standard evaluation data that they provide is one of the rate-limiting factors for the progress of biomedical text mining. Data suggest that one major factor affecting the use of a corpus outside of its home laboratory is the format in which it is distributed. This paper tests the hypothesis that corpus refactoring - changing the format of a corpus without altering its semantics - is a feasible goal, namely that it can be accomplished with a semi-automatable process and in a time effcient way. We used simple text processing methods and limited human validation to convert the Protein Design Group corpus into two new formats: WordFreak and embedded XML. We tracked the total time expended and the success rates of the automated steps. RESULTS: The refactored corpus is available for download at the BioNLP SourceForge website http://bionlp.sourceforge.net. The total time expended was just over three person-weeks, consisting of about 102 hours of programming time (much of which is one-time development cost) and 20 hours of manual validation of automatic outputs. Additionally, the steps required to refactor any corpus are presented. CONCLUSION: We conclude that refactoring of publicly available corpora is a technically and economically feasible method for increasing the usage of data already available for evaluating biomedical language processing systems. PMID- 17854504 TI - Characterization of the effect of sample quality on high density oligonucleotide microarray data using progressively degraded rat liver RNA. AB - BACKGROUND: The interpretability of microarray data can be affected by sample quality. To systematically explore how RNA quality affects microarray assay performance, a set of rat liver RNA samples with a progressive change in RNA integrity was generated by thawing frozen tissue or by ex vivo incubation of fresh tissue over a time course. RESULTS: Incubation of tissue at 37 degrees C for several hours had little effect on RNA integrity, but did induce changes in the transcript levels of stress response genes and immune cell markers. In contrast, thawing of tissue led to a rapid loss of RNA integrity. Probe sets identified as most sensitive to RNA degradation tended to be located more than 1000 nucleotides upstream of their transcription termini, similar to the positioning of control probe sets used to assess sample quality on Affymetrix GeneChip(R) arrays. Samples with RNA integrity numbers less than or equal to 7 showed a significant increase in false positives relative to undegraded liver RNA and a reduction in the detection of true positives among probe sets most sensitive to sample integrity for in silico modeled changes of 1.5-, 2-, and 4 fold. CONCLUSION: Although moderate levels of RNA degradation are tolerated by microarrays with 3'-biased probe selection designs, in this study we identify a threshold beyond which decreased specificity and sensitivity can be observed that closely correlates with average target length. These results highlight the value of annotating microarray data with metrics that capture important aspects of sample quality. PMID- 17854503 TI - Structure-function analysis of the retinoblastoma tumor suppressor protein - is the whole a sum of its parts? AB - Biochemical analysis of the retinoblastoma protein's function has received considerable attention since it was cloned just over 20 years ago. During this time pRB has emerged as a key regulator of the cell division cycle and its ability to block proliferation is disrupted in the vast majority of human cancers. Much has been learned about the regulation of E2F transcription factors by pRB in the cell cycle. However, many questions remain unresolved and researchers continue to explore this multifunctional protein. In particular, understanding how its biochemical functions contribute to its role as a tumor suppressor remains to be determined. Since pRB has been shown to function as an adaptor molecule that links different proteins together, or to particular promoters, analyzing pRB by disrupting individual protein interactions holds tremendous promise in unraveling the intricacies of its function. Recently, crystal structures have reported how pRB interacts with some of its molecular partners. This information has created the possibility of rationally separating pRB functions by studying mutants that disrupt individual binding sites. This review will focus on literature that investigates pRB by isolating functions based on binding sites within the pocket domain. This article will also discuss the prospects for using this approach to further explore the unknown functions of pRB. PMID- 17854505 TI - A conserved gene family encodes transmembrane proteins with fibronectin, immunoglobulin and leucine-rich repeat domains (FIGLER). AB - BACKGROUND: In mouse the cytokine interleukin-7 (IL-7) is required for generation of B lymphocytes, but human IL-7 does not appear to have this function. A bioinformatics approach was therefore used to identify IL-7 receptor related genes in the hope of identifying the elusive human cytokine. RESULTS: Our database search identified a family of nine gene candidates, which we have provisionally named fibronectin immunoglobulin leucine-rich repeat (FIGLER). The FIGLER 1-9 genes are predicted to encode type I transmembrane glycoproteins with 6-12 leucine-rich repeats (LRR), a C2 type Ig domain, a fibronectin type III domain, a hydrophobic transmembrane domain, and a cytoplasmic domain containing one to four tyrosine residues. Members of this multichromosomal gene family possess 20-47% overall amino acid identity and are differentially expressed in cell lines and primary hematopoietic lineage cells. Genes for FIGLER homologs were identified in macaque, orangutan, chimpanzee, mouse, rat, dog, chicken, toad, and puffer fish databases. The non-human FIGLER homologs share 38-99% overall amino acid identity with their human counterpart. CONCLUSION: The extracellular domain structure and absence of recognizable cytoplasmic signaling motifs in members of the highly conserved FIGLER gene family suggest a trophic or cell adhesion function for these molecules. PMID- 17854506 TI - OntologyWidget - a reusable, embeddable widget for easily locating ontology terms. AB - BACKGROUND: Biomedical ontologies are being widely used to annotate biological data in a computer-accessible, consistent and well-defined manner. However, due to their size and complexity, annotating data with appropriate terms from an ontology is often challenging for experts and non-experts alike, because there exist few tools that allow one to quickly find relevant ontology terms to easily populate a web form. RESULTS: We have produced a tool, OntologyWidget, which allows users to rapidly search for and browse ontology terms. OntologyWidget can easily be embedded in other web-based applications. OntologyWidget is written using AJAX (Asynchronous JavaScript and XML) and has two related elements. The first is a dynamic auto-complete ontology search feature. As a user enters characters into the search box, the appropriate ontology is queried remotely for terms that match the typed-in text, and the query results populate a drop-down list with all potential matches. Upon selection of a term from the list, the user can locate this term within a generic and dynamic ontology browser, which comprises the second element of the tool. The ontology browser shows the paths from a selected term to the root as well as parent/child tree hierarchies. We have implemented web services at the Stanford Microarray Database (SMD), which provide the OntologyWidget with access to over 40 ontologies from the Open Biological Ontology (OBO) website 1. Each ontology is updated weekly. Adopters of the OntologyWidget can either use SMD's web services, or elect to rely on their own. Deploying the OntologyWidget can be accomplished in three simple steps: (1) install Apache Tomcat 2 on one's web server, (2) download and install the OntologyWidget servlet stub that provides access to the SMD ontology web services, and (3) create an html (HyperText Markup Language) file that refers to the OntologyWidget using a simple, well-defined format. CONCLUSION: We have developed OntologyWidget, an easy-to-use ontology search and display tool that can be used on any web page by creating a simple html description. OntologyWidget provides a rapid auto-complete search function paired with an interactive tree display. We have developed a web service layer that communicates between the web page interface and a database of ontology terms. We currently store 40 of the ontologies from the OBO website 1, as well as a several others. These ontologies are automatically updated on a weekly basis. OntologyWidget can be used in any web-based application to take advantage of the ontologies we provide via web services or any other ontology that is provided elsewhere in the correct format. The full source code for the JavaScript and description of the OntologyWidget is available from http://smd.stanford.edu/ontologyWidget/. PMID- 17854507 TI - An action research protocol to strengthen system-wide inter-professional learning and practice [LP0775514]. AB - BACKGROUND: Inter-professional learning (IPL) and inter-professional practice (IPP) are thought to be critical determinants of effective care, improved quality and safety and enhanced provider morale, yet few empirical studies have demonstrated this. Whole-of-system research is even less prevalent. We aim to provide a four year, multi-method, multi-collaborator action research program of IPL and IPP in defined, bounded health and education systems located in the Australian Capital Territory (ACT). The project is funded by the Australian Research Council under its industry Linkage Program. METHODS/DESIGN: The program of research will examine in four inter-related, prospective studies, progress with IPL and IPP across tertiary education providers, professional education, regulatory and registration bodies, the ACT health system's streams of care activities and teams, units and wards of the provider facilities of the ACT health system. One key focus will be on push-pull mechanisms, ie, how the education sector creates student-enabled IPP and the health sector demands IPL oriented practitioners. The studies will examine four research aims and meet 20 research project objectives in a comprehensive evaluation of ongoing progress with IPL and IPP. DISCUSSION: IPP and IPL are said to be cornerstones of health system reforms. We will measure progress across an entire health system and the clinical and professional education systems that feed into it. The value of multi methods, partnership research and a bi-directional push-pull model of IPL and IPP will be tested. Widespread dissemination of results to practitioners, policymakers, managers and researchers will be a key project goal. PMID- 17854508 TI - Custom-designed orthopedic implants evaluated using finite element analysis of patient-specific computed tomography data: femoral-component case study. AB - BACKGROUND: Conventional knee and hip implant systems have been in use for many years with good success. However, the custom design of implant components based on patient-specific anatomy has been attempted to overcome existing shortcomings of current designs. The longevity of cementless implant components is highly dependent on the initial fit between the bone surface and the implant. The bone implant interface design has historically been limited by the surgical tools and cutting guides available; and the cost of fabricating custom-designed implant components has been prohibitive. METHODS: This paper describes an approach where the custom design is based on a Computed Tomography scan of the patient's joint. The proposed design will customize both the articulating surface and the bone implant interface to address the most common problems found with conventional knee-implant components. Finite Element Analysis is used to evaluate and compare the proposed design of a custom femoral component with a conventional design. RESULTS: The proposed design shows a more even stress distribution on the bone implant interface surface, which will reduce the uneven bone remodeling that can lead to premature loosening. CONCLUSION: The proposed custom femoral component design has the following advantages compared with a conventional femoral component. (i) Since the articulating surface closely mimics the shape of the distal femur, there is no need for resurfacing of the patella or gait change. (ii) Owing to the resulting stress distribution, bone remodeling is even and the risk of premature loosening might be reduced. (iii) Because the bone-implant interface can accommodate anatomical abnormalities at the distal femur, the need for surgical interventions and fitting of filler components is reduced. (iv) Given that the bone-implant interface is customized, about 40% less bone must be removed. The primary disadvantages are the time and cost required for the design and the possible need for a surgical robot to perform the bone resection. Some of these disadvantages may be eliminated by the use of rapid prototyping technologies, especially the use of Electron Beam Melting technology for quick and economical fabrication of custom implant components. PMID- 17854509 TI - Developing a web-based information resource for palliative care: an action research inspired approach. AB - BACKGROUND: General Practitioners and community nurses rely on easily accessible, evidence-based online information to guide practice. To date, the methods that underpin the scoping of user-identified online information needs in palliative care have remained under-explored. This paper describes the benefits and challenges of a collaborative approach involving users and experts that informed the first stage of the development of a palliative care website 1. METHOD: The action research-inspired methodology included a panel assessment of an existing palliative care website based in Victoria, Australia; a pre-development survey (n = 197) scoping potential audiences and palliative care information needs; working parties conducting a needs analysis about necessary information content for a redeveloped website targeting health professionals and caregivers/patients; an iterative evaluation process involving users and experts; as well as a final evaluation survey (n = 166). RESULTS: Involving users in the identification of content and links for a palliative care website is time-consuming and requires initial resources, strong networking skills and commitment. However, user participation provided crucial information that led to the widened the scope of the website audience and guided the development and testing of the website. The needs analysis underpinning the project suggests that palliative care peak bodies need to address three distinct audiences (clinicians, allied health professionals as well as patients and their caregivers). CONCLUSION: Web developers should pay close attention to the content, language, and accessibility needs of these groups. Given the substantial cost associated with the maintenance of authoritative health information sites, the paper proposes a more collaborative development in which users can be engaged in the definition of content to ensure relevance and responsiveness, and to eliminate unnecessary detail. Access to volunteer networks forms an integral part of such an approach. PMID- 17854510 TI - Highly active antiretroviral treatment and health related quality of life in South African adults with human immunodeficiency virus infection: A cross sectional analytical study. AB - BACKGROUND: Health Related Quality of Life (HRQoL) is an important outcome in times of Highly Active Antiretroviral Treatment (HAART). We compared the HRQoL of HIV positive patients receiving HAART with those awaiting treatment in public sector facilities in the Free State province in South Africa. METHODS: A stratified random sample of 371 patients receiving or awaiting HAART were interviewed and the EuroQol-profile, EuroQol-index and Visual Analogue Scale (VAS) were compared. Independent associations between these outcomes and HAART, socio-demographic, clinical and health service variables were estimated using linear and ordinal logistic regression, adjusted for intra-clinic clustering of outcomes. RESULTS: Patients receiving HAART reported better HRQoL for 3 of the 5 EuroQol-dimensions, for the VAS score and for the EuroQol index in bivariable analysis. They had a higher mean EuroQol index (0.11 difference, 95% confidence interval [CI] 0.04; 0.23), and were more likely to have a higher index (odds ratio 1.9, 95% CI 1.1; 1.3), compared to those awaiting HAART, in multivariate analysis. Higher mean VAS scores were reported for patients who were receiving HAART (6.5 difference, 95% CI 1.3; 11.7), were employed (9.1, 95% CI 4.3; 13.7) or were female (4.7, 95% CI 0.79; 8.5). CONCLUSION: HAART was associated with improved HRQoL in patients enrolled in a public sector treatment program in South Africa. Our finding that the EuroQol instrument was sensitive to HAART supports its use in future evaluation of HIV/AIDS care in South Africa. Longitudinal studies are needed to evaluate changes in individuals' HRQoL. PMID- 17854511 TI - Intraoperative radiotherapy (IORT) is an option for patients with localized breast recurrences after previous external-beam radiotherapy. AB - BACKGROUND: For patients suffering of recurrent breast cancer within the irradiated breast, generally mastectomy is recommended. The normal tissue tolerance does not permit a second full-dose course of radiotherapy to the entire breast after a second breast-conserving surgery (BCS). A novel option is to treat these patients with partial breast irradiation (PBI). This approach is based on the hypothesis that re-irradiation of a limited volume will be effective and result in an acceptable frequency of side effects. The following report presents a single center experience with intraoperative radiotherapy (IORT) during excision of recurrent breast cancer in the previously irradiated breast. METHODS: Between 4/02 and 11/06, 15 patients were treated for in-breast recurrences at a median of 10 years (3-25) after previous EBRT (10 recurrences in the initial tumor bed, 3 elsewhere in-breast failures, 2 invasive recurrences after previous DCIS). Additional 2 patients were selected for IORT with new primary breast cancer after previous partial breast EBRT for treatment of Hodgkin's disease. IORT with a single dose of 14.7 - 20 Gy 50 kV X-rays at the applicator surface was delivered with the Intrabeam-device (Carl Zeiss, Oberkochen, Germany). RESULTS: After a median follow-up of 26 months (1-60), no local recurrence occurred. 14 out of 17 patients are alive and free of disease progression. Two patients are alive with distant metastases. One patient died 26 months after BCS/IORT due to pulmonary metastases diagnosed 19 months after BCS/IORT. Acute toxicity after IORT was mild with no Grade 3/4 toxicities and cosmetic outcome showed excellent/good/fair results in 7/7/3 cases. CONCLUSION: IORT for recurrent breast cancer using low energy X-rays is a valuable option for patients with recurrent breast cancer after previous radiotherapy. PMID- 17854512 TI - Ice-water hand immersion causes a reflex decrease in skin temperature in the contralateral hand. AB - Cutaneous receptors stimulated by ice-water immersion of one hand will increase sympathetic nerve activity to the palm skin in the nonimmersed contralateral hand and reduce blood flow, reflecting on a decrease in skin surface temperature under a constant ambient environment. To test the hypothesis that gender might affect the contralateral vasoconstrictor response, we analyzed the spatiotemporal pattern of palm skin surface temperature during ice-water immersion for 10 min using thermography in eight males and eight females. As soon as the left hand was immersed in ice-water, palm skin temperature in the nonimmersed right hand quickly decreased in all subjects, particularly in the periphery of the digits and palm. The reduction in skin temperature was short-lasting in 63% of males and 38% of females, but it lasted throughout immersion in the remaining subjects. The average decrease in palm skin temperature was not significantly different between males and females, though it tended to be greater in males. The mean arterial blood pressure significantly increased and heart rate decreased during immersion in males, whereas no substantial cardiovascular changes were observed in females. Cold sensation was well coincident with the appearance of a reduction in the palm skin temperature. In consideration of all these results, we suggest that cutaneous cold stimuli increased skin sympathetic nerve activity in the nonimmersed hand and reduced skin blood flow. We also contend that gender difference in the contralateral vasoconstrictor response was denied because the time course and magnitude of the decrease in palm skin temperature were not different between males and females. PMID- 17854513 TI - A Cdk5 inhibitor enhances the induction of insulin secretion by exendin-4 both in vitro and in vivo. AB - Exendin-4 (Ex4) is a peptide found in the lizard Heloderma suspectum, and it has a high similarity to glucagon-like peptide 1 (GLP-1). It induces insulin secretion without the risk of hypoglycemic episodes. Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase that is predominantly expressed in neurons. Recent studies have shown that this kinase regulates glucose-stimulated insulin secretion. Cdk5 inhibition enhances insulin secretion under conditions of stimulation by high glucose, but not low glucose. In the present study, we examined whether R-roscovitine (R-ros), a Cdk5 inhibitor, enhances insulin secretion induced by Ex4. R-ros induced Ex4-dependent insulin secretion under conditions of high glucose, but not low glucose in MIN6B1 cells. The enhancement by R-ros was also observed in db/db mice, a mouse model of type 2 diabetes. Moreover, long-term treatment with Ex4 and R-ros significantly improved HbA1c compared with treatment using only Ex4. These results suggest that a co application of R-ros and Ex4 may become a promising therapy for the treatment of type 2 diabetes. PMID- 17854514 TI - Quantification of cardiac baroreflex function at rest and during autonomic stimulation. AB - The cardiac baroreflex constitutes an important mechanism mediating autonomic control of heart activity. Its function can be quantified by applying sequence analysis based on continuous recordings of blood pressure and heart rate. In this study, several indices derived from this method were compared regarding their suitability to estimate baroreflex function at rest and during autonomic stimulation. A cold pressor test was used to induce vagal withdrawal. Changes in the following indices evoked by this procedure were examined: baroreflex sensitivity (the extent of changes in heart period following blood pressure fluctuations), baroreflex effectiveness (the relative frequency in which the reflex responds to blood pressure fluctuations), and baroreflex power (the reflex operations in a defined period). The values of all indices decreased during autonomic stimulation. The strongest and most consistent effect, however, was observed for baroreflex sensitivity, suggesting that this parameter is the most sensitive to changes in parasympathetic tone among the three parameters. Baroreflex sensitivity also proved to differentiate between individuals with higher and lower resting blood pressure. Therefore, this index may best reflect the well-known involvement of the baroreflex in the long-term setting of blood pressure. Midrange correlations between the indices of baroreflex function suggest that they quantify similar, though not identical, aspects of baroreflex function. This study supports the use of sequence analysis as a reliable tool for the quantification of parasympathetic cardiac control. The sensitivity index must be considered the most relevant to quantify baroreflex function among the three parameters. PMID- 17854515 TI - Role of pharmacoepidemiology in evaluating prescription drug safety in pediatrics. AB - BACKGROUND: Pharmacoepidemiology is a discipline that applies epidemiological methodologies to the study of drug use, especially the safety of drug use in a large group of people. But this methodology has not been widely utilized to assess drug safety in pediatrics for children aged between 0 and 18 years. OBJECTIVES: (1) To describe current gaps in evaluating pediatric drug safety; (2) to use published examples demonstrating the value of pharmacoepidemiology in detecting and quantifying adverse drug events in pediatrics; (3) to review pharmacoepidemiological study designs, their strengths and limitations, and examples of their applications in the field of drug safety evaluation; and (4) to provide recommendations about selecting an appropriate study design and minimizing a major methodological limitation. OVERVIEW: Only about 20% of approved drugs are licensed for pediatric use, and many prescription drugs are used as 'off label' or 'unlicensed' pediatric treatments. Among this small percentage of licensed pediatric drugs, pre-marketing trials may not adequately address all drug-related safety issues in pediatrics. Consequently, an important gap exists in pediatric drug safety evaluation. Pharmacoepidemiology offers a number of advantages in detecting and quantifying adverse drug events in pediatrics. Each pharmacoepidemiological study design has its own strengths and limitations in the evaluation of drug safety. An appropriate study design depends on the underlying research question being addressed. Confounding by indication, the most serious and challenge form of confounding in pharmacoepidemiological designs, could lead to misleading claims about the relationship between drug use and the development of potential adverse drug events, and should be adequately controlled. CONCLUSIONS: Pharmacoepidemiology is a powerful methodology that offers many advantages to assess pediatric drug safety such as large sample size, long period of follow-up, and good generalizibility. But this methodology should be applied judiciously to maximize its potential. PMID- 17854517 TI - Natural cycle IVF: a question of semantics? AB - Recently there has been much discussion and presentation on IVF protocols using less stimulation or indeed none at all. Our experience with controlled natural cycle IVF over the last few years has convinced us that this is a powerful tool for many patients in the treatment of infertility. The protocol we employ has raised some questions as to whether it is natural cycle or stimulated cycle. We have reported a large series of cycles and seen no stimulatory effects of the medications used to control the cycle, thereby confirming our position that controlled natural cycle IVF is a valid option as an assisted reproduction treatment. PMID- 17854519 TI - Affordable IVF for developing countries. AB - Worldwide, more than 80 million couples suffer from infertility; the majority are residents of developing countries. Residents of developing countries encounter a lack of facilities at all levels of health care, but especially infertility diagnosis and treatment. Infertility defined as a disease has a much stronger negative consequence in developing countries compared with Western societies. Social isolation, economic deprivation and violence are commonly observed. Tubal infertility due to sexually transmitted diseases, unsafe abortion and post-partum pelvic infections are the main causes of infertility in developing countries. Very often those conditions are only treatable by assisted reproductive technologies. Although preventative measures are undoubtedly the most cost effective approach, not offering assisted reproduction is not an alternative. This study proposes a specially designed infertility care programme leading to cost-effective simplified assisted reproduction as a valid treatment protocol in developing countries when prevention or alternative methods have failed. Special attention should be given to avoid adverse outcomes such as ovarian hyperstimulation and multiple embryo pregnancy. PMID- 17854521 TI - Cell phones and male infertility: dissecting the relationship. AB - There has been a tremendous increase in the use of mobile phones in the past decade and concerns are growing about the possible hazardous effects of radio frequency electromagnetic waves (EMW) emitted by these devices on human health. Preliminary studies, though with limitations in study design, suggest a possible link between cell phone use and infertility. A recent study found that use of cell phones adversely affects the quality of semen by decreasing the sperm counts, motility, viability and morphology. Evidence of detrimental effect of mobile phones on male fertility is still equivocal as studies have revealed a wide spectrum of possible effects ranging from insignificant effects to variable degrees of testicular damage. Although previous studies suggested a role of cell phone use in male infertility, the mode of action of EMW emitted from cell phones on the male reproductive system is still unclear. EMW can affect the reproductive system via an EMW-specific effect, thermal molecular effect or combination of both. Studies performed on human males are scarce and therefore further studies with a careful design are needed to determine the effect of cell phone use on male-fertilizing potential. PMID- 17854523 TI - A prospective randomized study comparing coasting with GnRH antagonist administration in patients at risk for severe OHSS. AB - This work evaluated possible advantages of gonadotrophin-releasing hormone (GnRH) antagonist administration as an alternative to coasting in prevention of severe ovarian hyperstimulation syndrome (OHSS) in women undergoing IVF/ intracytoplasmic sperm injection. A prospective randomized study comparing coasting (group A) (n = 96) and GnRH antagonist administration (group B) (n = 94) in patients at risk of OHSS was performed. The primary outcome measure was high quality embryos. The secondary outcome measures were days of intervention, number of oocytes, pregnancy rate, number of cryopreserved embryos and incidence of severe OHSS. There were significantly more high quality embryos (2.87 +/- 1.2 versus 2.21 +/- 1.1; P < 0.0001), and more oocytes (16.5 +/- 7.6 versus 14.06 +/- 5.2; P = 0.02), in group B as compared with group A. There were more days of coasting as compared with days of antagonist administration (2.82 +/- 0.97 versus 1.74 +/- 0.91; P < 0.0001). In conclusion, GnRH antagonist was superior to coasting in producing significantly more high quality embryos and more oocytes as well as reducing the time until HCG administration. There was no significant difference in pregnancy rate between the two groups. No OHSS developed in either group. PMID- 17854524 TI - A heavy blow for British science. PMID- 17854525 TI - High-dose recombinant LH add-back strategy using high-dose GnRH antagonist is an innovative protocol compared with standard GnRH antagonist. AB - High daily doses of gonadotrophin-releasing hormone (GnRH) antagonists during the follicular phase of ovarian stimulation were associated with low implantation rates. To test if this occurred because of profound pituitary suppression, the pituitary response was suppressed with a high-dose GnRH antagonist and recombinant LH (rLH) was added back to correct the implantation rate. An open label, randomized, controlled, prospective clinical study in 60 patients undergoing IVF was performed. GnRH antagonist was initiated on day 6 of stimulation (2 mg/day) together with 375 IU rLH, and maintained until the day of HCG administration. Controls received 0.25 mg/day GnRH antagonist. Fluctuating LH concentrations were present on days 3 and 6 in both groups. This strong fluctuation continued on day 8 and on the day of HCG administration in the control (low-dose) group, where 30% of patients had LH concentrations <1 IU/l on the HCG day. The study (high-dose) group showed stable LH concentrations on day 8 and on the HCG day, with no LH surges. No clinical differences were found between groups. The LH add-back strategy (375 IU/day) rescued the adverse effects that high doses of GnRH imposed on implantation. These results suggest that rLH should be considered during ovarian stimulation with GnRH antagonist. PMID- 17854526 TI - Natural history of the mammalian oocyte. AB - Combining cryopreservation of immature oocytes with in-vitro growth/maturation techniques is the ambition of many IVF clinics. Whilst these techniques have been demonstrated in rodents their application to humans and domestic species has been slow. There are many technical reasons for the lack of progress in these species, but the major problem is that we have very little knowledge of how the oocyte acquires developmental competence during its growth within the follicle. The life history of the mammalian oocyte involves a complex series of co-ordinated developmental processes that in the human take place over several months. This review will consider: (i) growth and development of the oocyte; (ii) the newly regenerated debate on the existence of germ-line stem cells in the mammalian ovary; and (iii) strategies for producing oocytes in vitro. PMID- 17854527 TI - Predicting human embryo viability: the road to non-invasive analysis of the secretome using metabolic footprinting. AB - Infertility affects an increasing number of couples and for many the treatment of choice is IVF. However, the success rate remains relatively low, and, as typically two or more embryos are implanted, successful pregnancy often leads to multiple pregnancies with attendant complications. The major limitation in clinical IVF is the inability to predict which embryos are most viable, with the highest chance of implantation and development to a live baby. In principle, embryos can be selected for transfer based on data obtained at the genomic, transcriptomic, proteomic and/or metabolomic levels; however, these measurements cannot always be made directly on the embryo without invasive biopsy of cells. Alternative strategies are needed and this review considers the range of possibilities, with a focus on the analysis of the secretome from human embryos using metabolic footprinting. PMID- 17854528 TI - Reproductive oocyte/embryo genetic analysis: comparison between fluorescence in situ hybridization and comparative genomic hybridization. AB - Multiple displacement amplification (MDA) renders an increased quantity of genomic DNA available for comparative genomic hybridization (CGH), enabling it to be used to identify genomic imbalances in human blastomeres. The karyotypic lineage of 57 blastocysts derived from 11 ovum donors following ovarian stimulation was examined. CGH was performed on all first polar bodies, and linearly on corresponding second polar bodies and blastomeres. A diploid karyotype was propagated from the prefertilized oocyte to the embryo in 25 (44%) sets of analyses. In 32/57 sets (56%), aneuploidy was detected in the post fertilized zygotes/embryos and in nine (28%) of such cases the aneuploidy was 'chaotic' (> or =3 chromosomes). In 4/57 cases (7%) mitotic aneuploidy was observed. CGH and fluorescence in-situ hybridization (FISH) were concurrently performed on two blastomeres removed from each of 44 embryos obtained from four patients. In 43 (98%) of these embryos there was a direct karyotypic correlation between nine-probe commercial FISH and CGH. CGH identified > or =15% more chromosomal abnormalities than through FISH alone. The linear propagation using MDA-CGH, of the same karyotypic abnormalities that affected the oocyte of origin, in the corresponding embryos, coupled with the fact that CGH confirmed the aneuploidies identified through FISH, validates the accuracy and reliability of CGH technology. PMID- 17854530 TI - Removal of cervical mucus: effect on pregnancy rates in IVF/ICSI. AB - Cervical mucus may cover the embryo transfer catheter during passage of the cervical canal, interfering with the correct placement of the embryo(s) into the uterine cavity. The effect of removal of cervical mucus prior to embryo transfer in IVF/ intracytoplasmic sperm injection (ICSI) on live birth rate was studied. The study was set up as a single blind randomized controlled trial. Couples undergoing IVF/ICSI were randomly allocated to either removal of cervical mucus prior to embryo transfer, or a mock procedure. Randomization was done with stratification for age, cycle number and method of treatment. Primary outcome was live birth rate. A total of 317 couples were included and underwent 428 cycles, of which the outcome of 3 cycles was unknown. Baseline characteristics of both groups were comparable. Live birth occurred in 52 of 220 (24%) cycles in the treatment group and 42 of 205 (21%) cycles in the control group (risk difference 3%, 95% confidence interval-5- 11%). It is unlikely that removal of cervical mucus prior to embryo transfer has a significant effect on live birth rate. A small effect, however, cannot be excluded. PMID- 17854531 TI - Follicular fluid vascular endothelial growth factor and tumour necrosis factor alpha concentrations in patients with endometriosis undergoing ICSI. AB - The aim of this study was to investigate follicular fluid vascular endothelial growth factor (VEGF) and tumour necrosis factor alpha (TNFalpha) concentrations in endometriosis, and their effect on the outcome of intracytoplasmic sperm injection (ICSI). A prospective study was performed among patients who had either a laparoscopic diagnosis of endometriosis (n = 48) or who had normal laparoscopic findings with unexplained infertility (n = 43). The number of gonadotrophin units, peak oestradiol concentrations, number of oocytes retrieved, fertilization, cleavage and pregnancy rates, and number of embryos transferred, were the main outcome measurements. There was no difference in these parameters between the two study groups. Significantly higher concentrations of VEGF were found in the endometriosis group (P = 0.031), but there was no difference in TNFalpha concentrations. No relationship was found between VEGF and TNFalpha concentrations and ICSI outcome. Despite a higher concentration of intrafollicular VEGF in the endometriosis group, it was concluded that this parameter had no predictive value with respect to ICSI outcome. In addition, intrafollicular TNFalpha concentrations were not different in the endometriosis group and there was no relationship between VEGF or TNFalpha concentrations and the outcomes measured. PMID- 17854532 TI - Differential expression of follicular fluid cytokines: relationship to subsequent pregnancy in IVF cycles. AB - The objective of this study was to investigate the role of cytokines in the peri ovulatory follicular fluid (FF) during IVF cycles. FF from 112 women was obtained during oocyte retrieval for IVF. The concentrations of five cytokines [interleukin (IL)- 1beta, IL-6, IL-12, IL-13, and tumour necrosis factor alpha (TNFalpha )] were measured in FF and their concentrations compared among women who became pregnant and those who did not. Thirty-one endometriosis patients, 15 idiopathic infertility, 21 tubal factor infertility, 15 ovarian factor infertility, and 30 patients with male factor infertility were included. Interleukin-13 and TNFalpha were absent in the peri-ovulatory FF of all patients. Fifty-two patients achieved pregnancy, whereas 60 did not. Both pregnant and non pregnant groups were comparable for age, parity, ovarian stimulation parameters, fertilization rates, and embryo freezing rates. Concentrations of FF IL-1beta were not significantly different between pregnant and non-pregnant cycles. Concentrations of FF IL-6 were significantly higher in pregnant compared with non pregnant cycles (P = 0.0005). Concentrations of FF IL-12 were significantly lower in pregnant compared with non-pregnant cycles (P = 0.0002). Higher concentrations of IL-12 and lower concentrations of IL-6 in the peri-ovulatory FF are associated with a negative outcome in IVF treatment. Interleukins-12 and IL-6 are biological markers that appear to affect IVF outcome. PMID- 17854533 TI - Differential actions of FSH and LH during folliculogenesis. AB - In the gonadotrophin-dependent stage of follicular development, FSH- and LH signalling pathways play an obligatory role in follicle differentiation, selection and survival. Under the effect of LH the theca-interstitial cell layer acts as an androgen producer. Thus, androgen diffusing into the mural granulosa cell layer represents the substrate for FSH-induced aromatase for follicular oestradiol synthesis. This is the landmark 'two cell-two gonadotrophin' concept in the physiology of ovarian function in mammals. The increase in plasma FSH during luteo-follicular transition is the basis for follicle selection. The rise of FSH to the threshold concentration represents a critical condition for the growth of the most sensitive follicle in a given time frame of the last 14 days of the dominant follicle odyssey. The gonadotrophin-induced follicular oestradiol secretion inhibits pituitary secretion of FSH, which in turn causes the concentration of FSH in the developing cohort follicles to drop below threshold concentrations and the arrest of the development of the less FSH-sensitive follicle (FSH threshold and window concept). In the gonadotrophin-dependent phase of follicular development, LH also seems to acts within a critical window of the hormone concentration framed between the minimal threshold and a ceiling for the normal functions of the follicle unit. PMID- 17854534 TI - Will regeneration in plants and animals be applied in clinical medicine. PMID- 17854535 TI - Objective evaluation of the viability of cryopreserved oocytes. AB - Recent studies of fundamental cryobiology, empirical observations and more systematic clinical experiences have generated a renewed interest in oocyte cryopreservation. Poor survival rate has long been the limiting factor which has prevented widespread adoption of oocyte storage. Slow-cooling and vitrification protocols developed in the last few years have apparently solved this problem, ensuring high recovery of viable oocytes from liquid nitrogen storage. However, the definition of oocyte viability appears rather vague. In fact, post-storage survival as assessed on morphological criteria, indicated by the absence of overt cell degeneration, is not necessarily synonymous with viability. Despite its sensitivity to low temperatures, the meiotic spindle can be preserved after cryopreservation and its constitution after thawing can be monitored non invasively through polarized light microscopy. Assessment of oocyte cryopreservation via clinical parameters is a daunting task. Most studies are small and difficult to interpret because of confounding factors, such as age, patient selection and quality and strategy of use of the cryopreserved material. Some progress has been made, however, as suggested by recent experiences in which the implantation efficiency of embryos produced from thawed oocytes approaches that reported using cryopreserved embryos directly. PMID- 17854537 TI - Molecular methods for selection of the ideal oocyte. AB - Some recent strategies for identifying the ideal oocyte for insemination in assisted reproduction techniques are reviewed. Established methods of assessing the female gamete, such as morphological evaluation of oocytes and cytogenetic analysis of polar bodies using fluorescence in-situ hybridization, will soon be joined by more advanced cytogenetic methods such as the use of comparative genomic hybridization to improve understanding of oocyte genetics. It seems likely, however, that the greatest advances will originate from the evolution of molecular genetic technologies. The application of microarray technology to individual oocytes and their associated cumulus cells has recently been accomplished, providing a simultaneous assessment of activity for thousands of genes and revealing potential viability markers. Furthermore, improved equipment and optimized methods of mass spectrometry have provided sufficient sensitivity to allow proteomic profiles to be generated from single oocytes and embryos, while metabolomic investigations have searched for indicators of oocyte/embryo quality in spent culture medium. Techniques of this type may ultimately lead to non-invasive tests for oocyte quality revealing previously hidden information concerning both oocyte and embryo developmental competence. Once fully validated, these new approaches are expected to revolutionize oocyte and embryo selection, leading to improved implantation rates and higher probabilities of success using elective single embryo transfer. PMID- 17854538 TI - Low dose of HCG to prevent OHSS. PMID- 17854539 TI - Enhanced surveillance of hepatitis B infection in inner-western Sydney. AB - OBJECTIVES: We developed an enhanced surveillance system for hepatitis B to improve the detection of newly acquired cases and to collect epidemiological data. METHODS: The study was undertaken from February to June (inclusive) 2005 at the Sydney South West Area Health Service Eastern Zone Public Health Unit. A letter was sent to treating doctors on receipt of a notification, requesting additional information on cases. Cases identified by the treating doctors as newly acquired were followed up by telephone. RESULTS: There were 295 notifications of hepatitis B in the period, of which three were newly acquired infections. Only one of these three cases was identified through enhanced surveillance. Information on ethnicity was obtained. CONCLUSIONS: This enhanced surveillance system is of limited value as an ongoing process. We recommend that it be undertaken periodically to monitor the epidemiology of the disease. PMID- 17854540 TI - Prevalence of Mantoux positivity and annual risk of infection for tuberculosis in New South Wales prisoners, 1996 and 2001. AB - OBJECTIVES: This study compares the prevalence of Mantoux positivity among prisoners in NSW in 1996 and 2001 and examines factors associated with Mycobacterium tuberculosis infection. DESIGN: Cross-sectional random samples of prisoners, including a longitudinal cohort of prisoners screened in both 1996 and 2001. SETTING: 29 correctional centres. PARTICIPANTS: 747 men and 167 women participated in the 2001 NSW Inmate Health Survey; a cohort of 104 prisoners from the 1996 and 2001 NSW Inmate Health Surveys. RESULTS: The prevalence of Mantoux positivity remained stable between 1996 and 2001 (12% and 14%, p = 0.2), and increased among prisoners from Asian backgrounds (21% and 47%, p = 0.02). The annual risk of infection in the cohort among those detained continuously between 1996 and 2001 was 3.1%, and among recidivists it was 2.7% (p = 0.6). CONCLUSION: The risk of M. tuberculosis infection for Australian prisoners is assessed to be approximately four times higher than that for the community, however there is no attributable risk to the prison environment itself. PMID- 17854541 TI - Recent substance use and high levels of psychological distress among secondary school students in New South Wales. AB - In 2002, the NSW Department of Health, in conjunction with The Cancer Council NSW, carried out the NSW School Students Health Behaviours Survey. The methodology and summary descriptive results have been previously described [NSW Department of Health. The health behaviours of secondary school students in New South Wales 2002. N S W Public Health Bull 2004; 15(S-2): 1-86]. In the survey, 18% of NSW secondary school students reported high levels of psychological distress, 30% reported recently using alcohol, 13% reported recently using tobacco, and 9% reported recently using cannabis. With regard to the other illicit drugs, 2.0% reported recently using amphetamines, 1.0% cocaine, 1.4% hallucinogens (LSD, heroin) and 1.9% ecstasy. The survey did not, however, examine associations between substance use and high levels of psychological distress. These associations are described in this article. PMID- 17854542 TI - A discussion of the potential benefits to injury surveillance through inclusion of date of injury in hospitalisation data in New South Wales and Australia. AB - Most hospitalised injury cases have sudden onset at a specific time and date, due to a well-defined external cause (eg, a road crash). Date of injury is not presently recorded in routine hospital separations data in NSW or Australia, though it is in New Zealand. Benefits of adding date of injury to the Inpatient Statistics Collection would include: more accurate estimation of the population incidence of serious injury; better assessment of the health system utilisation and costs attributable to injurious events; and better linkage of hospital data with other data relevant to injury measurement and control (eg, road crash data). PMID- 17854543 TI - A review of the efficacy of human Q fever vaccine registered in Australia. AB - BACKGROUND: Q fever remains an important occupational zoonosis in rural Australia. Although Q fever vaccine is recommended in high-risk occupational groups, its availability has been limited in recent years. METHOD: A literature review of the efficacy of the human Q fever vaccine registered in Australia was conducted. RESULTS: Seven relevant vaccine efficacy studies were identified but no large double-blind, randomised, placebo-controlled studies have been conducted. Vaccine efficacy has ranged from 83-100% but limitations of study designs hamper a precise estimate of vaccine efficacy. CONCLUSION: Despite the shortcomings of efficacy studies, the Q fever vaccine available in Australia has considerable protective benefit in established high-risk environments, particularly of an occupational nature. PMID- 17854544 TI - [Effects of Wenyang Chubi Decoction on connective tissue growth factor and collagen-I in a mouse model of scleroderma]. AB - OBJECTIVE: To study the effects of Wenyang Chubi Decoction (WYCBD), a compound traditional Chinese herbal medicine, on connective tissue growth factor (CTGF) and collagen-I (COL-I) in a mouse model of scleroderma. METHODS: Scleroderma was induced in BALB/c mice by daily local injection of bleomycin for three weeks and the mice were randomly divided into untreated, WYCBD-treated and normal saline (NS) treated groups, with another group of BALB/c mice as normal control. WYCBD and NS were given orally for one month respectively. Histopathology in the skin and lungs of the mice were examined. The CTGF and COL-I expressions in the skin or skin lesions were detected by immunohistochemical Elivision assay. RESULTS: The expression levels of CTGF and COL-I in the untreated group were significantly higher than those in the normal control group (P<0.05). Compared with the NS treated group, the WYCBD-treated group had significant improvement in the skin and lung histopathology and remarkably decreased expression levels of CTGF and COL-I (P<0.05). CONCLUSION: Scleroderma mice showed high expressions of CTGF and COL-I in the skin. WYCBD had the effects of decreasing the CTGF and COL-I expressions and improving the skin fibrosis. PMID- 17854545 TI - [Framework and practice of network-based studies for Chinese herbal formula]. AB - The ZHENG (syndrome of traditional Chinese medicine) oriented effects and the multiple-targets' mechanism are the main challenges encountered by recent researches for Chinese herbal formula. Using methods of bioinformatics and systems biology, we proposed a biological network-based framework for understanding the mechanism of Chinese herbal formula, and reviewed our studies under this framework which aimed to explore the relationship between Chinese herbal formula and corresponding ZHENGs, as well as the synergism of herbal combinations. These studies include the network construction for cold or heat ZHENG and its relationship with herbal formula of hot or cold nature, the biological network construction of angiogenesis, and the network regulation-based emergent property of an herbal combination with anti-angiogenesis synergism extracting from the cold formula. It is shown that the ZHENG-oriented effects and the herbal synergism can be nicely explicated by such network-based approaches. Thus, the network-based drug combination discovery, as well as the "traditional Chinese medicine bioinformatics (TCMB)" and "TCM computational systems biology" combining with computational and experimental approaches, is conceivable and can open a new avenue for understanding Chinese herbal formula. PMID- 17854546 TI - [Influence of Lithospermum on pregnancy]. AB - Lithospermum has been widely used in clinic for a long time. It can lower the levels of follicle stimulating hormone and luteinizing hormone in blood serum and inhibit ovulation, thus causing infertility. Due to its effect of lowering chorionic gonadotropin, restraining the development of corpus luteum graviditatis and interfering the growth of uterus and the supply of embryotrophy, Lithospermum has been confirmed to be effective in termination of pregnancy and herb abortion. Therefore Lithospermum can not be used in those who intend to conceive or do not need to terminate pregnancy. The authors suggest that the influence of Lithospermum on pregnancy should be studied objectively and should be emphasized in clinical teaching of traditional Chinese medicine to ensure the correct and reasonable application of Lithospermum. PMID- 17854547 TI - [Clinical outcome assessment and the effect measure]. AB - Effect of clinical intervention on human body is multistage and multifaceted, involving physiology, psychology, social function and the surrounding resources, etc. Therefore, the range of clinical outcome assessment includes patient, his or her family and care giver. The evaluation of clinical intervention mainly focuses on its effectiveness, safety and health economics. Effects of clinical interventions are measured by comparisons of the outcome of intervention and control groups. Different effect measures come from different comparisons. PMID- 17854548 TI - [An evaluation method for analysis of correlation between traditional Chinese medicine syndrome and seasonal changes of weather based on information entropy]. AB - OBJECTIVE: A method based on dubious condition of information entropy was introduced and applied to discuss a complexity problem in the analysis of correlation between traditional Chinese medicine (TCM) syndrome and season. METHODS: Eight hundred and seventy one cases of chronic virus hepatitis B (hepatitis B) with TCM clinical data were analyzed by information entropy method. RESULTS: It was found that hepatitis B with Yin deficiency of liver and kidney happened more often in summer than in other seasons. CONCLUSION: It is inferred that the difference of seasons may influence the variation of TCM syndromes. PMID- 17854549 TI - [Visceral syndrome differentiation in traditional Chinese medicine and the changes of nutrition status or blood gas analysis in patients with chronic obstructive pulmonary disease]. AB - OBJECTIVE: To investigate the relationship between visceral syndrome differentiation in traditional Chinese medicine (TCM) and the changes of nutrition status or blood gas analysis in patients with chronic obstructive pulmonary disease (COPD). METHODS: Sixty patients with COPD in stable phase were divided into dysfunction of lung (DL, n=20) group, dysfunction of lung and spleen (DLS, n=16) group and dysfunction of lung, spleen and kidney (DLSK, n=24) group according to syndrome differentiation of TCM. Moreover, the basic electric rhythm, percentage of bradygastria in electrogastrogram (EGG), ratio of actual body weight (ABW) to ideal body weight (IBW) and serum albumin level were determined to evaluate the nutrition status of the patients with COPD. Blood gas analysis was made too. RESULTS: The basic electric rhythm values in the DL, DLS and DLSK groups were (56.20+/-13.24)%, (47.38+/-10.24)% and (41.35+/-10.01)%, respectively. Compared with the DL group, the basic electric rhythm values in the DLS and DLSK groups decreased obviously (P<0.05). The percentages of bradygastria in the DL, DLS and DLSK groups were (45.18+/-18.13)%, (46.31+/-15.83)% and (49.90+/-17.54)%, respectively, and there were no differences among the three groups (P>0.05). The incidence rates of ABW/IBW<90% in the DL, DLS and DLSK groups were 50%, 75% and 54.17%, respectively, and there were no differences among the three groups (P>0.05). The incidence rates of serum albumin less than 35 g/L were 20%, 37.5% and 54.17%, respectively, and there were no differences among the three groups (P>0.05). PO2 in the DLS group [(63.56+/-15.06) mmHg] and DLSK group [(63.17+/-19.05) mmHg] were decreased as compared with the DL group [(78.15+/-16.63) mmHg] (P<0.05). PCO2 in the DL, DLS and DLSK groups were (42.25+/-12.46) mmHg, (48.60+/-17.60) mmHg and (49.97+/-13.43) mmHg respectively, and there were no differences among the three groups (P>0.05). CONCLUSION: Several dysfunction organs described in TCM were involved in COPD followed by the increased severity, hypoxemia and PCO2. Dysfunction of gastrointestinal tract and malnourishment took place accordingly. PMID- 17854550 TI - [Multifactor analysis of syndrome differentiation in traditional Chinese medicine and clinical correlative factors in gastric cancer]. AB - OBJECTIVE: The research is aimed at investigating the developing rule and the relationship between syndrome differentiation in traditional Chinese Medicine (TCM) and clinical factors of gastric cancer so as to guide clinical work and indicate prognosis. METHODS: We collected the medical records and the information of four diagnostic methods of 325 cases of gastric cancer sufferers in the way of clinical epidemiological survey, and divided them into 6 syndromes including dysfunction of spleen, disharmony of liver and stomach, blood stagnation in stomach, yin deficiency of stomach, phlegm dampness stagnation and deficiency of both qi and blood. Then we used logistic regression analysis to analyze the relationship between syndrome differentiation and clinical-related factors such as age, gender, Karnofsky score and clinical stage, etc. RESULTS: The syndrome spleen dysfunction is a dominant one among the syndromes of stomach cancer. Disharmony of liver and stomach always happens in early stage of stomach cancer and is frequently seen in women. Patients with syndrome of phlegm dampness stagnation or deficiency of both qi and blood have lower Karnofsky score and poorer living quality. Syndromes of blood stagnation in stomach and yin deficiency of stomach show no relationship with the clinical factors in this research. CONCLUSION: Syndrome differentiation in TCM of gastric cancer is related to some clinical factors to a certain extent. PMID- 17854551 TI - [Serum proteomics study of chronic gastritis with dampness syndrome in traditional Chinese medicine]. AB - OBJECTIVE: To explore microcosmic information in chronic gastritis dampness syndrome by using serum proteomics of patients with chronic gastritis dampness syndrome. METHODS: Serum proteomics of 18 dampness syndrome cases, 17 non dampness syndrome cases in chronic gastritis patients and 8 normal controls were analyzed by surface enhanced laser desorption/ionization-time of flight (SELDI TOF) protein-chip. RESULTS: There was a high expression trend in three ratios of charge (of an electron) to mass (M/S) of 3.2 kD, 6.4 kD and 8.1 kD of protein expression spectrum from patients with chronic gastritis dampness syndrome, and the wave peak value was over 10 units. There was a low expression trend in above mentioned sites of protein expression spectrum from patients with chronic gastritis non-dampness syndrome and normal group. The wave peak value of patients with chronic gastritis non-dampness syndrome was about or below 10 units, and the wave peak value in normal group was below 5 units. CONCLUSION: There exists a certain significance to explore biologic theory basis of chronic gastritis dampness syndrome by analyzing the serum proteomics. PMID- 17854552 TI - [Effects of three compounds extracted from Tripterygium wilfordii Hook on angiogenesis in chick chorioallantoic membrane]. AB - OBJECTIVE: To investigate the effects of three compounds extracted from Tripterygium wilfordii Hook (TW) on angiogenesis in the chick chorioallantoic membrane (CAM). METHODS: Fifty fresh Hongkong Mahua chicken eggs were divided into five groups: PBS-treated group, TW1-, TW2- and TW3-treated groups and Rg3 treated group. After disinfection, the eggs were incubated for six days in a constant temperature box with the temperature being controlled within 37.8 degrees C, then exposed CAM, laid the filter papers with specimen on the CAM, and the eggs were incubated for another two days. CAM was fixed with the mixture of methyl alcohol and acetone at room temperature for about 15 min, and then cutting the CAM, taking photos and observing the angiogenesis in the CAM. RESULTS: There were many CAM vessels in the PBS-treated group and the blood vessel net could be seen clearly. The number of CAM vessels in the TW1-, TW2- and TW3-treated groups (10 microg/egg) was much less than that in the PBS-treated group. Furthermore, the frame of the vessels was not clear, and the color was obscure. Inhibition rates of angiogenesis in the TW1-, TW2- and TW3-treated groups were 80%, 60% and 100% respectively, while the inhibition rate of angiogenesis in the Rg3-treated group (10 microg/egg) was only 10%. CONCLUSION: TW1, TW2 and TW3 can obviously restrain the angiogenesis in CAM and still need further study. PMID- 17854553 TI - [Mechanism of salvianolate in preventing postoperative intestinal adhesion in rats]. AB - OBJECTIVE: To observe the effects of salvianolate on rats with postoperative intestinal adhesion and to explore the prevention mechanism. METHODS: Forty SD male rats with intestinal adhesion were randomly divided into four groups: untreated group, low-dose salvianolate-treated group (12 mg/kg), medium-dose salvianolate-treated group (24 mg/kg) and high-dose salvianolate-treated group (48 mg/kg), with another ten SD male rats as normal control. Intraperitoneal injection of glucose was administered to the rats in the normal control group and the untreated group, and intraperitoneal injection of salvianolate was administered to the rats in the low-, medium- and high-dose salvianolate-treated groups. They were all treated for 8 days and once a day. On the eighth day after surgery the blood samples of each group were collected. Grades of intestinal adhesion were ranked by macroscopic observation. The adhesive tissues between viscera and belly wall were taken for pathological observation. The levels of interleukin-1beta (IL-1beta), interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) were determined by enzyme linked immunosorbent assay. RESULTS: Salvianolate can significantly reduce the extent of postoperative intestinal adhesion, obviously decrease the levels of IL-1beta, TNF-alpha and inhibit the hyperplasy of fibrous connective tissue. However, there was no significant impact on the level of IL-4. CONCLUSION: Salvianolate can reduce the extent of postoperative intestinal adhesion, decrease the expression of IL-1beta and TNF alpha and inhibit the hyperplasy of fibrous connective tissue. This may be the mechanism of salvianolate in preventing intestinal adhesion. PMID- 17854554 TI - [Effects of Jianpi Bushen Huoxue recipe on hematopoietic cell apoptosis in a mouse model of aplastic anemia]. AB - OBJECTIVE: Adopting methods of cell culture to explore the effects and mechanisms of Jianpi Bushen Huoxue Prescription (JPBSHXP), a traditional Chinese compound herbal medicine for strengthening spleen, reinforcing kidney and activating blood circulation, in inhibiting hematopoietic cells apoptosis in a mouse model of aplastic anemia (AA). METHODS: Blood serum of AA mice was made from an AA mouse model. Blood serums containing different traditional Chinese compound herbal medicine were made from rats after intragastric administration of JPBSHXP and its related decoctions, respectively. Bone marrow cells of normal mice were incubated by these blood serums for 24 hours, respectively. The apoptosis of the bone marrow cells were assayed by flow cytometry and transmission electron microscopy (TEM). RESULTS: It was indicated that the bone marrow cells of normal mice incubated with blood serum of AA mice displayed typical apoptosis. The apoptosis rates of bone marrow cells of the AA mice incubated by blood serum containing different traditional Chinese herbal medicine were decreased. The effect of Bushen (reinforcing kidey) Recipe was better than Jianpi (strengthening spleen) Recipe and Huoxue (activating blood circulation) Recipe, while the effect of JPBSHXP was the best. TEM results showed that the effect of Bushen Recipe was better than that of the Jianpi Recipe and the Huoxue Recipe, while the effect of JPBSHXP was the best. CONCLUSION: JPBSHXP and its related decoctions can significantly decrease the apoptosis rate of bone marrow mononuclear cells of the AA mice. It is inferred that JPBSHXP can promote bone marrow hematogenesis. PMID- 17854555 TI - [Effects of Astragalus on expression of renal angiopoietin receptor Tie-2 in diabetic rats]. AB - OBJECTIVE: To study the expression of angiopoietin receptor Tie-2 in the renal tissue of diabetic rats and the effects of Astragalus. METHODS: SD rats were randomly divided into normal control group, diabetes group and Astragalus-treated group. The expression of receptor Tie-2 in the renal tissue was assessed by using real-time quantitative polymerase chain reaction and immunohistochemical method. RESULTS: Glomerule Tie-2 protein expression was significantly elevated in the diabetes group as compared with the normal control group (P<0.01). Glomerule Tie 2 protein expression in the Astragalus-treated group was decreased as compared with the diabetes group (P<0.01). CONCLUSION: Tie-2 may play an important role in the pathogenesis of the early stage diabetic renal injury. The reno-protection effect of Astragalus may be mediated by down-regulating the expression of Tie-2 in the kidney tissue of diabetic rats. PMID- 17854556 TI - [Effects of Huanglian Jiedu Decoction on phosphatidylinositol-3-kinase expression in target tissues of type 2 diabetic rats]. AB - OBJECTIVE: To observe the effects of Huanglian Jiedu Decoction (HLJDD), a traditional Chinese compound herbal medicine, on p85 mRNA and protein expressions of phosphatidylinositol-3-kinase (PI-3K) in target tissues (skeletal muscular and adipose tissues) in rats with type 2 diabetes mellitus (T2DM) and to investigate the molecular mechanism of HLJDD in treating T2DM. METHODS: The male Wistar rats were injected with streptozotocin (STZ) 30 mg/kg through tail vein, and fed with high-fat and high-caloric diets to induce T2DM. Then the rats were randomly divided into untreated group, aspirin-treated group and HLJDD group, and treated correspondingly. Meanwhile, a group of normal animals without any treatment was set up for normal control group. Ten weeks later, serum fasting blood glucose (FBG), serum fasting insulin (FINS) and oral glucose tolerance test (OGTT) were routinely determined. The expressions of PI-3K p85 mRNA and protein in skeletal muscle and adipose tissue were determined with RT-PCR and Western blotting before and after insulin treatment. RESULTS: Compared with the untreated group, the FBG and OGTT levels in T2DM rats treated with HLJDD decreased significantly (P<0.05). The FINS in HLJDD group was lower than that in the normal control group (P<0.05), but was not significantly different from that in the untreated group. The PI-3K p85 mRNA and protein expressions in HLJDD group obviously increased, as compared with those in the untreated group. CONCLUSION: The effect of HLJDD in treating T2DM was probably associated with its improvement of PI-3K p85 mRNA and protein expressions in skeletal muscle and adipose tissue of the T2DM rats. PMID- 17854557 TI - [Effect of electroacupuncture and diet adjusting on insulin resistance in rats with nutrition obesity]. AB - OBJECTIVE: To study the effects of electroacupuncture and diet adjusting on insulin resistance in rats with nutrition obesity, and the role of electroacupuncture and diet adjusting in the treatment of obesity. METHODS: Obesity was induced in rats by high-fat diet. Rats with nutrition obesity were randomly divided into high-fat diet (HD) group, high-fat diet plus electroacupuncture (HA) group, normal diet (ND) group and normal diet plus electroacupuncture (NA) group, with another group of SD rats as normal control (NC). After 15 days, all the rats' body weight and length were measured, the Lee's index was calculated, and the levels of total cholesterol (TC), triglycerides (TG), free fatty acid (FFA), fasting plasma glucose (FPG), fasting insulin (FINS) and tumor necrosis factor-alpha (TNF-alpha) were detected. RESULTS: Compared with the HD group, food intake, body weight and viscera fat weight of the rats with nutrition obesity in the HA group and the NA group were markedly reduced (P<0.05). The levels of blood serum TC, FFA and IR index in the NA group were obviously lower than those in the HD group (P<0.01). The levels of TNF-alpha and FINS in the NA group were lower than those in the HD group (P<0.05). CONCLUSION: Electroacupuncture plus diet adjusting can decrease the levels of serum TNF-alpha and FINS of the obesity rats, and improve the state of insulin resistance. PMID- 17854558 TI - [Effects of Baobaole oral liquid on neuron excitability of feeding center in anorectic rats]. AB - OBJECTIVE: To investigate the effects of Baobaole oral liquid on neuronal excitability in lateral hypothalamic area (LHA) and ventromedial hypothalamic nuclear (VMN) in anorectic rats. METHODS: The anorectic rat model was established by feeding with special prepared forage for a week, and then Baobaole oral liquid, a liquid extract of a compound traditional Chinese medicine for activating spleen, was administered once a day for 3 weeks. Finally, extracellular recording from LHA and VMN neurons in rats were made in order to characterize their responses to gastric vagal nerve stimulation and intravenous injection of glucose in the normal, untreated, and Baobaole-treated groups. RESULTS: There was no statistical difference in response characteristics of LHA neurons to gastric vagal stimulation among 3 groups. The duration of VMN neuron excitation response to gastric vagal nerve stimulation in the untreated group was significantly longer than that of the normal control group (P<0.01), while the required stimulation intensity was significantly decreased (P<0.01). Moreover, among the neurons responding to the gastric vagal stimulation in the untreated group, the number of glycemia-sensitive neurons decreased in LHA and increased in VMN (P<0.01). The gastric vagal stimulation induced neuron responses in LHA and VMN of the Baobaole-treated group were not significantly changed as compared with the normal control group (P<0.01), and neither were the intravenous injection of glucose induced responses. CONCLUSION: Baobaole oral liquid can modulate the sensitivity of LHA and VMN neurons to the peripheral signal and make the coordination between LHA and VMN neurons in order to improve the appetite of anorectic rats. PMID- 17854559 TI - [Content of somatostatin and cholecystokinin-8 in hypothalamus and colons in a rat model of spleen-deficiency syndrome]. AB - OBJECTIVE: To investigate the changes of neuropeptides content in a rat model of spleen-deficiency syndrome. METHODS: Rats were randomly divided into three groups: normal group, untreated group and treatment group. There were ten rats in each group. Spleen-deficiency syndrome was induced by intragastrically administration of rhubarb concentrate in rats of the untreated and treatment group. The rats in the treatment group were intragastrically administered with Sijunzi decoction, a traditional Chinese compound herbal medicine for strengthening spleen and supporting qi. Normal saline was intragastrically administered to the rats in the normal and untreated groups. The somatostatin (SS) and cholecystokinin-8 (CCK-8) content in hypothalamus and colons was detected by the method of radioimmunoassay and the D-xylose content in urine was also detected. RESULTS: The CCK-8 content in hypothalamus of the untreated group was higher than that of the normal group (P<0.05). SS and CCK-8 content in colons of the untreated group was higher than that of the normal group (P<0.05). The CCK 8 content in colons of the untreated group was lower than that of the treatment group (P<0.05). The excretion rate of D-xylose in the untreated group was lower than that of the normal group (P<0.05). CONCLUSION: The disorder of neuroendocrine regulation in rats with spleen-deficiency syndrome may be chiefly responsible for "spleen-deficency and dysfunction of spleen" in traditional Chinese medicine. PMID- 17854560 TI - [Effects of melittin on expressions of mitochondria membrane protein 7A6, cell apoptosis-related gene products Fas and Fas ligand in hepatocarcinoma cells]. AB - OBJECTIVE: To observe the effects of melittin on the expressions of mitochondria membrane protein 7A6, cell apoptosis-related gene products Fas and Fas ligand (FasL) in hepatocarcinoma cells in vitro and to study the mechanisms of melittin in inducing apoptosis of hepatocarcinoma cells. METHODS: BEL-7402 cell line was treated with melittin in vitro. The expressions of mitochondria membrane protein 7A6, cell apoptosis-related gene products Fas and FasL were detected by flow cytometry. Fas and FasL mRNAs were analyzed by reverse transcription polymerase chain reaction (RT-PCR) assay. RESULTS: The expression rates of mitochondria membrane protein 7A6 of BEL-7402 hepatocarcinoma cells in 8, 16, 32 microg/ml melittin-treated and control groups were 4.89%, 17.74%, 11.45% and 1.02%, respectively. The expression of Fas protein was up-regulated by melittin, while FasL expression did not change. RT-PCR results showed that Fas mRNA expression was up-regulated by 32 microg/ml melittin and FasL mRNA expression was not observed. CONCLUSION: The effects of melittin in inducing hepatocarcinoma cell apoptosis may be related with up-regulating the expressions of mitochondria membrane protein 7A6 and Fas protein. PMID- 17854561 TI - [Protection of Tianshen Yizhi Recipe against low expression of nicotinic receptor and neurotoxicity induced by beta-amyloid peptide]. AB - OBJECTIVE: To investigate the inhibition effects of Tianshen Yizhi Recipe (TSYZR), a compound traditional Chinese herbal medicine, on decreased expression of nicotinic acetylcholine receptor (nAChR) and the neurotoxicity as well as lipid peroxidation induced by beta-amyloid peptide (Abeta) in human SH-SY5Y neuroblastoma cells. METHODS: The SH-SY5Y cells were treated by a certain concentration of TSYZR, and then exposed to Abeta(25-35). Methyl thiazolyl tetrazolium reduction assay was carried out to understand the influences of the drugs on cellular viability. Expressions of nAChR subunits (alpha3 and alpha7) at protein and mRNA levels were detected by Western-blotting and reverse transcription polymerase chain reaction, respectively. Lipid peroxidation was measured by thiobarbituric acid to observe the capacity of antioxidant of the drugs. RESULTS: TSYZR at a safe concentration could increase alpha7 protein in the cells, inhibit decreased expressions of alpha3 and alpha7 nAChR subunit proteins, prevent lower expression of alpha7 mRNA in SH-SY5Y cells induced by Abeta, reduce the neurotoxicity and lipid peroxidation resulting from Abeta, but had no significant effect on the lower expression of alpha3 mRNA. CONCLUSIONS: TSYZR can up-regulate the expression of alpha7 nAChR subunit protein and prevent decreased expressions of nAChRs and neurotoxicity as well as lipid peroxidation induced by Abeta. This drug may play an important therapeutic role in treatment of Alzheimer disease. PMID- 17854562 TI - [Effects of total saponins of Panax japonicus on human leukemic HL-60 cells]. AB - OBJECTIVE: To study the effects of total saponins of Panax japonicus (TSPJ) on human leukemic HL-60 cells. METHODS: Human leukemic HL-60 cells were cultured in vitro. The cancer cell vigor was detected by using cell counting kit-8. Nitroblue tetrazolium (NBT) was used for measuring cell reduction. The cell cycle and the expression of differentiation antigen CD11b were detected by flow cytometry. RESULTS: Compared with the negative control group, TSPJ in different concentrations could decrease the vigor of HL-60 cells and the number of cells in S phase and up-regulate the CD11b expression, while the numbers of NBT positive cells and cells in G(0)/G(1) phase in the different concentrations of TSPJ treated groups were increased. CONCLUSION: TSPJ can inhibit the HL-60 cell growth in vitro. Its mechanism may be related to inhibiting proliferation and inducing cell differentiation and cycle arrest. PMID- 17854563 TI - In vivo effect of casticin on acute inflammation. AB - OBJECTIVE: To investigate the anti-inflammatory effect of casticin of Fructus Viticis. METHODS: Observations were made on the anti-inflammatory effect of casticin in the models of acute inflammation in vivo. RESULTS: Casticin inhibited significantly xylene-induced mouse ear edema, egg albumen-induced rat paw edema and acetic acid-induced mouse vascular permeability. CONCLUSION: Casticin has significant anti-inflammatory effect on acute inflammation, which is probably related to the inhibition of the inflammation factors. Casticin is the effective constituent contributing to the anti-inflammatory effect of Fructus Viticis. PMID- 17854564 TI - [Effect of isoflavones in regulating the transcription of target genes through estrogen receptors]. AB - OBJECTIVE: To observe the transcriptional regulation of the two isoflavones genistein and daidzein on target genes. METHODS: In this study, we used ERalpha or ERbeta over-expressing Hela cells to observe the transcriptional regulation of genistein and daidzein on ERE reporter gene with calcium-phosphate method, and furthermore observing the effects of phytoestrogen antagonist ICI 182780 on their activation. RESULTS: Our results showed that both genistein and daidzein could activate ERE receptor gene through ERalpha and ERbeta, and these effects could be blocked by ICI 182780. CONCLUSION: Both genistein and daidzein can mimic estrogen's effect to activate the transcription of target genes through binding to the ERs. PMID- 17854565 TI - [Total glucosides of peony as adjuvant therapy for prevention of cardiac allograft rejection in rats]. AB - OBJECTIVE: To evaluate the role of total glucosides of peony (TGP) as adjuvant therapy for prevention of cardiac allograft rejection in rats. METHODS: Rats with cardiac allograft were randomly divided into control group, tacrolimus-treated group, TGP-treated group and tacrolimus plus TGP-treated group. Graft survival time was observed. Allografts in some cases were examined by histological study seven days after transplantation. At the same time, the levels of CD4(+) and CD8(+) T cell subsets in peripheral blood were examined by using flow cytometry; the hepatic function and renal function of recipients were also tested. RESULTS: The graft survival time of the tacrolimus-treated group and tacrolimus plus TGP treated group was (11.14+/-1.57) d and (13.57+/-1.99) d, respectively. The graft survival time of the tacrolimus plus TGP-treated group was longer than that of the tacrolimus-treated group (P<0.05). The histological study showed that the rejection of the tacrolimus plus TGP-treated group was slighter than that of the tacrolimus-treated group. The levels of CD4(+) T cell subset in the peripheral blood of the tacrolimus-treated and tacrolimus plus TGP-treated groups were (38.71+/-5.15)% and (32.43+/-4.39)% respectively 7 days after transplantation. The level of CD4(+) T cell subset in the tacrolimus plus TGP-treated group was lower than that in the tacrolimus-treated group (P<0.05). The level of CD8(+) T cell subset and the hepatic and renal function had no significant differences between the tacrolimus-treated group and the tacrolimus plus TGP-treated group. CONCLUSION: Effects of tacrolimus plus TGP in prevention of rejection are better than tacrolimus monotherapy in rats with cardiac allograft and without increasing side effects. PMID- 17854566 TI - [Effects of different nursing methods in treatment of phlebitis caused by cinobufacini injection]. PMID- 17854567 TI - [Clinical research of manipulation therapy for lower cervical instability]. PMID- 17854568 TI - [Internal opening incision with harmonic scalpel, remaining and tunnel thread dragging methods in surgical management of posterior horseshoe fistula]. PMID- 17854569 TI - [Clinical observation on the effects of Chinese herbal drugs and acupuncture plus traditional Chinese herbal medicine in treatment of 295 patients with insomnia]. PMID- 17854570 TI - [Discrimination and interpretation of errors in statistical analysis of qualitative data in medical papers]. PMID- 17854571 TI - Self-criticism on the English translation of traditional Chinese medicine. PMID- 17854572 TI - Premature graduation of children in child restraint systems: an observational study. AB - This study investigated the use and misuse of child restraint systems (CRS) in Flanders (Belgium). Observations were conducted at a random sample of primary school and recreation areas. In total 1376 children were observed. A logistic regression model was constructed in order to determine the variables involved. The parameter-estimates of this model have shown that children are more often restrained when the driver buckles up, the ride takes less than 1h, the children are younger, the children sit in the front seat of the car, a recreational area is the destination of the trip and there are less than five children in the car. Also premature graduation to CRS was analysed. More than half of the children are not appropriately restrained, according to their age, weight or height. Improper shoulder belt use (putting the shoulder belt behind the back or under the arm) was observed in 8.99% of the children being restrained with high back booster seats, in 32.73% of the children being restrained with backless booster seats and finally in 19.07% of the children being restrained with seat belts. The risk of incorrectly using the shoulder belt increases when children are prematurely graduated in a CRS. The results are discussed in the light of other studies on this matter. PMID- 17854573 TI - The role of motorcyclist and other driver behaviour in two types of serious accident in the UK. AB - Motorcycle accidents have somewhat different characteristics from accidents involving other classes of road user. They include in particular 'right of way' accidents, and accidents involving loss of control on curves or bends. A sample of 1790 accident cases was considered, including 1003 in detail, from UK midland police forces, involving motorcyclists of all ages, and covering the years 1997 2002 inclusive. Significant differences were discovered in the sample with respect to types of accidents involving motorcyclists (and their blameworthiness). There seems to be a particular problem surrounding other road users' perception of motorcycles, particularly at junctions. Such accidents often seem to involve older drivers with relatively high levels of driving experience who nonetheless seem to have problems detecting approaching motorcycles. Motorcyclists themselves seem to have far more problems with other types of accident, such as those on bends or curves. The implications of these findings are discussed. PMID- 17854574 TI - General deterrence effects of U.S. statutory DUI fine and jail penalties: long term follow-up in 32 states. AB - INTRODUCTION: We examined effects of state statutory changes in DUI fine or jail penalties for firsttime offenders from 1976 to 2002. METHODS: A quasi experimental time-series design was used (n=324 monthly observations). Four outcome measures of drivers involved in alcohol-related fatal crashes are: single vehicle nighttime, low BAC (0.01-0.07g/dl), medium BAC (0.08-0.14g/dl), high BAC (>/=0.15g/dl). All analyses of BAC outcomes included multiple imputation procedures for cases with missing data. Comparison series of non-alcohol-related crashes were included to efficiently control for effects of other factors. Statistical models include state-specific Box-Jenkins ARIMA models, and pooled general linear mixed models. RESULTS: Twenty-six states implemented mandatory minimum fine policies and 18 states implemented mandatory minimum jail penalties. Estimated effects varied widely from state to state. Using variance weighted meta analysis methods to aggregate results across states, mandatory fine policies are associated with an average reduction in fatal crash involvement by drivers with BAC>/=0.08g/dl of 8% (averaging 13 per state per year). Mandatory minimum jail policies are associated with a decline in single-vehicle nighttime fatal crash involvement of 6% (averaging 5 per state per year), and a decline in low-BAC cases of 9% (averaging 3 per state per year). No significant effects were observed for the other outcome measures. CONCLUSIONS: The overall pattern of results suggests a possible effect of mandatory fine policies in some states, but little effect of mandatory jail policies. PMID- 17854575 TI - Predictors of seatbelt use in American Indian motor vehicle crash trauma victims on and off the reservation. AB - OBJECTIVES: American Indians (AI's) have the lowest rate of seatbelt use in the nation, putting them at significant risk for motor vehicle crash (MVC) morbidity and mortality. This study compares seatbelt use in victims of level one trauma crashes presenting from on and off AI reservations. Predictors of seatbelt use were evaluated as well. We hypothesized that AI's in crashes on a reservation would have lower rates of seatbelt use, even compared to AI's in crashes from off the reservation. METHODS: This is a retrospective cohort study of consecutive MVC victims presenting to a level one trauma facility in Phoenix, Arizona from July 2003 to June 2005. Inclusion criteria were age >11 and transported directly from the crash; struck pedestrians were excluded. Inter-facility transports were also excluded, as these patients would likely represent a sicker population, possibly introducing bias. Characteristics of those patients (sex, race, location of crash, alcohol and seatbelt use) were analyzed in univariate and multivariate logistic regression. RESULTS: Data were collected on 2339 patients. Three hundred ninety-two were excluded, leaving 1947 (83%) available for analysis. AI's had lower rates of seatbelt use compared to all other races. Additionally, AI's on a reservation were less likely to wear seatbelts than those off a reservation (25.9% versus 42.7%). However, when tested in a multivariate analysis with alcohol as a covariate, race and location became insignificant. Low seatbelt use by AI's on the reservation was primarily associated with alcohol use. CONCLUSION: In this analysis, alcohol, rather than race or location, is the overriding predictor of seatbelt use. This study compared patients that were in crashes, and only those triaged to a level one trauma facility. If we assume unbelted passengers are more severely injured, this would bias our results. The application of these data may help direct future public service efforts to increase seatbelt use in target populations. PMID- 17854576 TI - Working in light vehicles--a review and conceptual model for occupational health and safety. AB - Occupational light vehicle (OLV) use is the leading cause of work related traumatic deaths in Westernised countries. Previous research has focused primarily on narrow contexts of OLV-use such as corporate fleet vehicles. We have proposed a comprehensive systems model for OLV-use to provide a framework for identifying research needs and proposing policy and practice interventions. This model presents the worker as the locus of injury at the centre of work- and road related determinants of injury. Using this model, we reviewed existing knowledge and found most studies focused only on company car drivers, neglecting OLV-users in non-traditional employment arrangements and those using other vehicle types. Environmental exposures, work design factors and risk and protective factors for the wider OLV-user population are inadequately researched. Neither road- nor work related policy appropriately addresses OLV-use, and population surveillance relies largely on inadequate workers compensation insurance data. This review demonstrates that there are significant gaps in understanding the problem of OLV use and a need for further research integrating public health, insurance and road safety responses. The model provides a framework for understanding the theory of OLV-use OHS and guidance for urgently needed intervention research, policy and practice. PMID- 17854577 TI - A joint econometric analysis of seat belt use and crash-related injury severity. AB - This paper formulates a comprehensive econometric structure that recognizes two important issues in crash-related injury severity analysis. First, the impact of a factor on injury severity may be moderated by various observed and unobserved variables specific to an individual or to a crash. Second, seat belt use is likely to be endogenous to injury severity. That is, it is possible that intrinsically unsafe drivers do not wear seat belts and are the ones likely to be involved in high injury severity crashes because of their unsafe driving habits. The preceding issues are considered in the current research effort through the development of a comprehensive model of seat belt use and injury severity that takes the form of a joint correlated random coefficients binary-ordered response system. To our knowledge, this is the first instance of such a model formulation and application not only in the safety analysis literature, but in the econometrics literature in general. The empirical analysis is based on the 2003 General Estimates System (GES) data base. Several types of variables are considered to explain seat belt use and injury severity levels, including driver characteristics, vehicle characteristics, roadway design attributes, environmental factors, and crash characteristics. The results, in addition to confirming the effects of various explanatory variables, also highlight the importance of (a) considering the moderating effects of unobserved individual/crash-related factors on the determinants of injury severity and (b) seat belt use endogeneity. From a policy standpoint, the results suggest that seat belt non-users, when apprehended in the act, should perhaps be subjected to both a fine (to increase the chances that they wear seat belts) as well as mandatory enrollment in a defensive driving course (to attempt to change their aggressive driving behaviors). PMID- 17854578 TI - The risk of traffic accidents after prescriptions of carisoprodol. AB - OBJECTIVE: Carisoprodol, a drug used for acute lower back pain, may cause psychomotor impairment. We wanted to investigate if patients using carisoprodol had increased risk of being involved in a traffic accident. METHODS: Data were retrieved from three population-based registries for the period April 2004 September 2005. The Norwegian Prescription Database contained individual information on all dispensed drugs at all pharmacies outside hospitals. The Norwegian Road Accident Registry contained information on all drivers involved in motor vehicle accidents with person injury. The Norwegian Central Population Registry was used to control for emigration or death. The accident incidence among carisoprodol exposed and unexposed subjects was compared by standardized incidence ratio. RESULTS: Having a prescription for carisoprodol dispensed increased the standardized incidence ratio for being involved in an accident with person injury to 3.7 (95% CI 2.9-4.8) the first week after the date of dispensing. This was similar to diazepam (2.8; 2.2-3.6), but higher than for salbutamol (1.1; 0.6-1.8). CONCLUSIONS: Patients receiving carisoprodol seem to have an increased risk of being involved in traffic accidents involving person injury. The study gives support to earlier work published on the impairing effects of carisoprodol. PMID- 17854579 TI - Acceptability and concurrent validity of measures to predict older driver involvement in motor vehicle crashes: an Emergency Department pilot case-control study. AB - INTRODUCTION: Older drivers have one of the highest motor vehicle crash (MVC) rates per kilometer driven, largely due to the functional effects of the accumulation, and progression of age-associated medical conditions that eventually impact on fitness-to-drive. Consequently, physicians in many jurisdictions are legally mandated to report to licensing authorities patients who are judged to be medically at risk for MVCs. Unfortunately, physicians lack evidence-based tools to assess the fitness-to-drive of their older patients. This paper reports on a pilot study that examines the acceptability and association with MVC of components of a comprehensive clinical assessment battery. OBJECTIVES: To evaluate the acceptability to participants of components of a comprehensive assessment battery, and to explore potential predictors of MVC that can be employed in front-line clinical settings. METHODS: Case-control study of 10 older drivers presenting to a tertiary care hospital emergency department after involvement in an MVC and 20 age-matched controls. RESULTS: The measures tested were generally found to be acceptable to participants. Positive associations (p50% patients. METHODS: Participants underwent 5-day baseline and 5-day treatment periods; gastrointestinal transit (by validated scintigraphy) and bowel function (by daily diaries) were assessed. Treatment effects were compared using analysis of covariance (baseline colonic transit as covariate) with pairwise comparisons of each dose vs placebo. RESULTS: There was a significant overall treatment effect on ascending colon emptying half-time (P = .015) and overall colonic transit at 48 hours (P = .02) but not overall transit at 24 hours (P = ns), with a significant acceleration by linaclotide 1000 microg vs placebo (P = .004 and P = .01, respectively) but no significant effect of linaclotide 100-microg dose. There were significant overall treatment effects on stool frequency, stool consistency, ease of passage, and time to first bowel movement with a strong dose response for stool consistency (overall, P < .001). No safety issues were identified. CONCLUSIONS: In women with constipation predominant irritable bowel syndrome, linaclotide 1000 microg once daily significantly accelerated ascending colonic transit and altered bowel function. Further randomized controlled trials of clinical efficacy of linaclotide are warranted. PMID- 17854591 TI - Risk of peptic ulcer hospitalizations in users of NSAIDs with gastroprotective cotherapy versus coxibs. AB - BACKGROUND & AIMS: The primary strategies to reduce the risk of serious gastropathy caused by traditional nonsteroidal anti-inflammatory drugs (NSAIDs) are use of a coxib or concurrent use of a proton pump inhibitor or double-dose histamine-2 receptor antagonist. However, the relative clinical effectiveness of these therapeutic alternatives is understudied. METHODS: We studied peptic ulcer hospitalizations in a cohort of Tennessee Medicaid enrollees between 1996 and 2004. To decrease potential "channeling" bias, the study included only new episodes of prescribed NSAID or coxib use and controlled for multiple baseline risk factors for upper gastrointestinal disease. There were 234,010 and 48,710 new episodes of NSAID and coxib use, respectively, with 363,037 person-years of follow-up and 1223 peptic ulcer hospitalizations. RESULTS: Current users of NSAIDs with no gastroprotective cotherapy had an adjusted incidence of peptic ulcer hospitalizations of 5.65 per 1000 person-years, 2.76 (95% confidence interval, 2.35-3.23) times greater than that for persons not currently using either NSAIDs or coxibs. This risk was reduced by 39% (16%-56%, 95% CI) for current users of NSAIDs with gastroprotective cotherapy and 40% (23%-54%) for current users of coxibs without such cotherapy. Concurrent users of NSAIDs and proton pump inhibitors had a 54% (27%-72%) risk reduction, very similar to the 50% (27%-66%) reduction for concurrent users of proton pump inhibitors and coxibs. CONCLUSIONS: These findings suggest that coprescribing a proton pump inhibitor with an NSAID is as effective as use of a coxib for reducing the risk of NSAID-induced gastropathy. PMID- 17854592 TI - Neuropeptide s receptor 1 gene polymorphism is associated with susceptibility to inflammatory bowel disease. AB - BACKGROUND & AIMS: The neuropeptide S receptor (NPSR1) gene has been associated recently with asthma and maps in a region of chromosome 7 previously linked also to inflammatory bowel disease (IBD). NPSR1 is expressed on the epithelia of several organs including the intestine, and appears to be up-regulated in inflammation. We tested NPSR1 gene polymorphism for association with IBD and verified whether the expression of its 2 major isoforms (NPSR1-A and NPSR1-B) is altered in the intestine of IBD patients. METHODS: Eight NPSR1 polymorphisms were genotyped in 2490 subjects from 3 cohorts of IBD patients and controls from Italy, Sweden, and Finland. Real-time polymerase chain reaction and immunohistochemistry were used to quantify NPSR1 messenger RNA (mRNA) and protein expression in intestinal biopsy specimens from IBD patients and controls. RESULTS: Global analysis of the whole dataset identified strong association of a NPSR1 haplotype block with IBD (P = .0018) and its 2 major forms: Crohn's disease (CD) (P = .026) and ulcerative colitis (UC) (P = .003). Genetic effects caused by individual haplotypes were identified mainly for the predisposing haplotype H2 in CD (P = .0005) and the protective haplotype H8 in UC (P = .003). NPSR1 mRNA and protein levels were increased in IBD patients compared with controls, and the risk haplotype H2 correlated with higher expression of both NPSR1-A (P = .024) and NPSR1-B (P = .047) mRNAs. CONCLUSIONS: NPSR1 polymorphism is associated with IBD susceptibility. Specific NPSR1 alleles might act as genetic risk factors for chronic inflammatory diseases of the epithelial barrier organs. PMID- 17854593 TI - Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. AB - BACKGROUND & AIMS: Norfloxacin is highly effective in preventing spontaneous bacterial peritonitis recurrence in cirrhosis, but its role in the primary prevention of this complication is uncertain. METHODS: Patients with cirrhosis and low protein ascitic levels (<15 g/L) with advanced liver failure (Child-Pugh score > or = 9 points with serum bilirubin level > or = 3 mg/dL) or impaired renal function (serum creatinine level > or = 1.2 mg/dL, blood urea nitrogen level > or = 25 mg/dL, or serum sodium level < or = 130 mEq/L) were included in a randomized controlled trial aimed at comparing norfloxacin (35 patients) vs placebo (33 patients) in the primary prophylaxis of spontaneous bacterial peritonitis. The main end points of the trial were 3-month and 1-year probability of survival. Secondary end points were 1-year probability of development of spontaneous bacterial peritonitis and hepatorenal syndrome. RESULTS: Norfloxacin administration reduced the 1-year probability of developing spontaneous bacterial peritonitis (7% vs 61%, P < .001) and hepatorenal syndrome (28% vs 41%, P = .02), and improved the 3-month (94% vs 62%, P = .003) and the 1-year (60% vs 48%, P = .05) probability of survival compared with placebo. CONCLUSIONS: Primary prophylaxis with norfloxacin has a great impact in the clinical course of patients with advanced cirrhosis. It reduces the incidence of spontaneous bacterial peritonitis, delays the development of hepatorenal syndrome, and improves survival. PMID- 17854594 TI - Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients. AB - BACKGROUND & AIMS: Knowledge of factors regulating transcriptional activity of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) may help in understanding mechanisms of viral decay and how these processes are thwarted in chronically HBV-infected patients. METHODS: Liver biopsies from 119 treatment naive chronically infected patients (42 HBeAg-positive and 77 HBeAg-negative) were determined for HBV transcriptional and replicative activity. RESULTS: Significantly lower median serum HBV DNA (-4 log), intrahepatic HBV DNA (-2 log), and cccDNA (-1 log) amounts were measured in HBeAg-negative versus HBeAg-positive patients. Despite a good correlation found between intrahepatic amounts of progeny virions and serum HBV DNA in all patients, cccDNA levels did not correlate with serum titers in HBeAg-negative individuals. Analysis of HBV RNA transcripts showed that impaired virion productivity in HBeAg-negative individuals was due to lower steady-state levels of pregenomic RNA produced per cccDNA. Interestingly, preS/S RNA levels and serum HBsAg concentrations did not differ between HBeAg-positive and HBeAg-negative patients when normalized for cccDNA contents, showing that subviral particle production was not impaired in HBeAg-negative patients and correlated with cccDNA levels. Although the majority of HBeAg-negative individuals harbored cccDNA with common precore and/or basal core promoter mutations, occurrence of these variants was not responsible for reduced viral replication. Instead, replacement of wild-type cccDNA with core promoter mutants reestablished high virion productivity. CONCLUSIONS: Lower viremia in HBeAg-negative individuals is not only due to lower cccDNA content but also to impaired virion productivity, which can arise without emergence of HBeAg variants and without affecting HBsAg production. PMID- 17854595 TI - Inflammation and apoptosis in Clostridium difficile enteritis is mediated by PGE2 up-regulation of Fas ligand. AB - BACKGROUND & AIMS: Clostridium difficile toxin A causes acute inflammation and fluid secretion in experimental animals and patients with C difficile infection. We previously reported that toxin A increased cyclooxygenase-2/prostaglandin E(2) (PGE(2)) expression and apoptosis in human colonocytes. Here, we assessed the role of secreted PGE(2) in inflammation and enterocyte apoptosis in toxin A enteritis. METHODS: Effects of PGE(2) and PGE(2) blockade on toxin A-induced apoptosis of human colonocytes (NCM460) and of PGE(2) or toxin A on the Fas ligand (FasL) induction were analyzed by flow cytometry and Western blot. Functional activity of elevated FasL on colonocytes was assessed by coculture of colonocytes with Fas bearing Jurkat T cells. The involvement of PGE(2)-dependent Fas/FasL activation in toxin A enteritis was further assessed in either scid or FasL and Fas deficient mice. RESULTS: Inhibition of cyclooxygenase-2 by NS-398 and of PGE(2) using a blocking antibody markedly attenuated apoptosis in colonocytes exposed to toxin A. Enhanced expression and release of FasL followed PGE(2) or toxin A exposure in vivo and in vitro and also was significantly attenuated by treatment with NS-398 and PGE(2) blocking antibody. PGE(2) acting through an EP1 receptor activated nuclear factor-kappaB, which induced transcription of FasL. Toxin A enteritis was accompanied by increased cellular infiltration, fluid secretion, and mucosal damage in control mice, but this response was markedly reduced in both Fas(-/-) and FasL(-/-) mice. CONCLUSIONS: Toxin A enteritis involves release of PGE(2), which activates the Fas/FasL system, causing enterocyte apoptosis and inflammation. PMID- 17854596 TI - Exogenous serotonin regulates proliferation of interstitial cells of Cajal in mouse jejunum through 5-HT2B receptors. AB - BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) are required for normal gastrointestinal motility. Loss of ICC is associated with several motility disorders. The mechanisms modulating ICC survival and proliferation are poorly understood. This study aimed to establish whether 5-hydroxytryptamine (5-HT) plays a role in regulating ICC proliferation. METHODS: Expression of 5-HT receptor mRNA was investigated in muscle strips, in purified populations of ICC, and in identified single cells. The effect of 5-HT(2B) receptor ligands on ICC numbers was studied in primary cell cultures. Proliferation of ICC was determined by counting Ki67-positive cells in culture. RESULTS: Of the 5-HT receptors known to be involved in proliferation, 5-HT(2B) receptor mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in jejunal muscle, whereas 5 HT(1A), 5-HT(1D), and 5-HT(2C) receptor mRNAs were not. 5-HT(2B) receptor mRNA was found in single ICC and cells purified by flow cytometry. Exogenous 5-HT (1 micromol/L) increased (66% +/- 9%, P < .005) ICC numbers in culture. The 5-HT(2) receptor antagonist, ritanserin, and the 5-HT(2B) receptor antagonist, SB204741, inhibited the effect of 5-HT. The 5-HT(2B) receptor agonist BW 723C86 induced a concentration-dependent increase in ICC number (50% +/- 6% at 50 nM, P < .04) and increased ICC proliferation (25% +/- 3% vs 19 +/- 1% in controls, P < .03). CONCLUSIONS: These studies establish that 5-HT(2B) receptors are expressed on ICC. Exogenous 5-HT regulates ICC numbers through 5-HT(2B) receptors in part by increasing ICC proliferation. The 5-HT(2B) receptor may serve as a novel pathway to regulate ICC numbers. PMID- 17854597 TI - A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer. AB - BACKGROUND & AIMS: Helicobacter pylori is the main cause of peptic ulceration and gastric adenocarcinoma. The vacuolating cytotoxin gene, vacA, is a major determinant of virulence. Two naturally polymorphic sites in vacA, the signal region and midregion, are well-characterized determinants of toxicity and markers of pathogenesis. The aim of this study was to characterize a new vacA polymorphic site, the intermediate (i) region. METHODS: The vacA i-region was identified and characterized by constructing isogenic vacA exchange mutants and determining their vacuolating activity on HeLa, AGS, and RK13 cell lines. The vacA i-region types of H pylori isolates from patients undergoing routine endoscopy were determined by nucleotide sequencing and allele-specific polymerase chain reaction. RESULTS: Two i-region types were identified, i1 and i2, and both were common among 42 Western clinical isolates. Interestingly, only naturally occurring s1/m2 strains varied in i-type; s1/m1 and s2/m2 strains were exclusively i1 and i2, respectively. Vacuolation assays showed that i-type determined vacuolating activity among these s1/m2 strains, and exchange mutagenesis confirmed that the i-region itself was directly responsible. Using a simple i-region polymerase chain reaction-based typing system, it was shown for 73 Iranian patients that i1-type strains were strongly associated with gastric adenocarcinoma (P < 10(-3)). Finally, logistic regression analysis showed this association to be independent of, and larger than, associations of vacA s- or m type or cag status with gastric adenocarcinoma. CONCLUSIONS: Together these data show that the vacA i-region is an important determinant of H pylori toxicity and the best independent marker of VacA-associated pathogenicity. PMID- 17854598 TI - Viral quasi-species evolution during hepatitis Be antigen seroconversion. AB - BACKGROUND & AIMS: Although viral quasi-species evolution may be related to pathogenesis of disease, little is known about this in hepatitis B virus (HBV); consequently, we aimed to evaluate the evolution of HBV quasi-species in patients with well-characterized clinical phenotypes of chronic hepatitis B. METHODS: Four cohorts of well-defined clinical phenotypes of chronic hepatitis B, hepatitis Be antigen (HBeAg) seroconverters (spontaneous seroconverters and interferon-induced seroconverters) and nonseroconverters (controls and interferon nonresponders) were followed during 60 months on average. Serum from 4 to 5 time points was used for nested polymerase chain reaction, cloning, and sequencing of the precore/core gene (20 clones/sample). Only patients with genotype B were used. Sequences were aligned using Clustal X, then serial-sample unweighted pair grouping method with arithmetic means phylogenetic trees were constructed using Pebble 1.0 after which maximum likelihood estimates of pairwise distances under a GTR + I + G model was assessed. Viral diversity and substitution rates were then estimated. RESULTS: Analysis of 3386 sequences showed that HBeAg seroconverters had 2.4-fold higher preseroconversion viral sequence diversity (P = .0183), and 10-fold higher substitution rate (P < .0001) than did nonseroconverters, who had persistently low viral diversity (3.6 x 10(-3) substitutions/site) and substitution rate (2.2 x 10(-5) substitutions x site(-1) x month(-1)). After seroconversion, there was a striking increase in viral diversity. Most seroconverters had viral variants that showed evidence of positive selection, which was seen mainly after seroconversion. CONCLUSIONS: The high viral diversity before a reduction in HBV DNA and before HBeAg seroconversion could either be related to occurrence of stochastic mutations that lead to a break in immune tolerance or to increased immune reactivity that drives escape mutations. PMID- 17854599 TI - Evidence against a role for NADPH oxidase modulating hepatic vascular tone in cirrhosis. AB - BACKGROUND & AIMS: Increased hepatic vascular resistance in cirrhosis is in part due to reduced nitric oxide (NO) bioavailability. This is related to insufficient NO synthesis from endothelial nitric oxide synthase and to enhanced NO scavenging by superoxide radicals (O(2)(-)). Nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase is an important source of O(2)(-) that increases vascular tone in different cardiovascular disorders. Thus, our aims were to study the molecular and biochemical state of NADPH-oxidase in cirrhotic livers and to investigate its possible role in modulating hepatic vascular tone in cirrhosis. METHODS: NADPH oxidase expression and enzymatic activity were determined in control (n = 8) and CCl(4)-cirrhotic (n = 8) rat livers. Additional control (n = 6) and CCl(4) cirrhotic (n = 10) rats were treated with apocynin (a selective NADPH-oxidase inhibitor) or its vehicle. Mean arterial pressure, portal pressure, and superior mesenteric arterial blood flow were measured in vivo. Moreover, hepatic endothelial function was evaluated in isolated and perfused rat livers by dose response curves to acetylcholine. In addition, in 6 control and 6 cirrhotic human livers NADPH-oxidase activity and expression were evaluated. RESULTS: Rat cirrhotic livers had no increased NADPH-oxidase protein expression or activity in relation to control livers. NADPH-oxidase inhibition did not modify splanchnic or systemic hemodynamics in control or cirrhotic rats and did not improve the impaired endothelial-dependent vasodilatory response to acetylcholine of cirrhotic livers. Human cirrhotic livers also did not exhibit increased NADPH oxidase expression or activity. CONCLUSIONS: Our study shows that NADPH-oxidase activity is decreased in the cirrhotic livers and therefore cannot explain increased hepatic O(2)(-), endothelial dysfunction, and increased vascular tone in cirrhotic livers. PMID- 17854600 TI - Direct intestinal cholesterol secretion contributes significantly to total fecal neutral sterol excretion in mice. AB - BACKGROUND & AIMS: Hepatobiliary secretion is generally believed to be an integral step in the pathway of cholesterol excretion from the body. Here we have investigated the validity of this paradigm in mice. METHODS: Cholesterol balance was assessed by measuring intake, excretion, and biliary output in different mouse models. Direct secretion of cholesterol from the luminal side of enterocytes was studied by perfusion of isolated segments of the small intestine in mice. RESULTS: Cholesterol input and output measurements in different mouse models revealed that fecal neutral sterol excretion was higher than the sum of dietary cholesterol intake and biliary cholesterol secretion indicating the existence of an alternative pathway. Here we show that substantial amounts of cholesterol can be secreted directly by enterocytes. Transintestinal cholesterol secretion is a specific process observed throughout the small intestine (proximal > medial > distal). Secretion depended on the presence of a cholesterol acceptor and was strongly stimulated by bile salts and phospholipids. The capacity of the pathway was sufficient to account for the missing cholesterol in the balance studies. The contribution of this pathway to cholesterol excretion in mice is approximately twice that of the biliary pathway. CONCLUSIONS: In mice, the intestine plays a significant role in removal of cholesterol from the body. PMID- 17854601 TI - RB loss abrogates cell cycle control and genome integrity to promote liver tumorigenesis. AB - BACKGROUND & AIMS: The retinoblastoma (RB) tumor suppressor is functionally inactivated in most hepatocellular carcinomas (HCC), although the mechanisms by which RB suppresses liver tumorigenesis are poorly defined. We investigated the impact of RB loss on carcinogen-induced liver tumorigenesis. METHODS: Mice harboring liver-specific RB ablation and normal littermates were exposed to the hepatocarcinogen diethylnitrosamine (DEN). The influence of RB loss on liver tumorigenesis was assessed by evaluating tumor multiplicity, proliferation, and genome integrity within tumors arising in RB-deficient and wild-type livers. In silico analyses were used to probe the association between gene expression signatures for RB loss and chromosomal instability and the ability of genes up regulated by RB loss to predict the survival of human HCC patients. RESULTS: RB deficiency significantly increased tumor multiplicity in livers exposed to DEN. Although hepatocytes in nontumor regions of DEN-exposed livers were quiescent regardless of RB status, tumors arising in RB-deficient livers were significantly more proliferative than those in normal livers and expressed high levels of RB/E2F target genes. Analysis of genes up-regulated by RB loss demonstrated significant overlap with a gene expression signature associated with chromosomal instability. Correspondingly, tumors arising in RB-deficient livers were significantly more likely to harbor hepatocytes exhibiting altered ploidy. Finally, gene expression analysis of human HCCs demonstrated that elevated expression of RB-regulated genes independently predicts poor survival. CONCLUSIONS: RB deletion in the mouse liver enhances DEN-induced tumorigenesis, associated with increased hepatocyte proliferation and compromised genome integrity. Evaluation of RB status may be a useful prognostic factor in human HCC. PMID- 17854602 TI - Eradication therapy for Helicobacter pylori. AB - Eradication therapy for Helicobacter pylori is recommended in a number of clinical conditions. In this article, we discuss the epidemiology and cellular mechanisms that result in antimicrobial resistance, the results of current eradication therapies, and new approaches to the management of Helicobacter pylori infection. PMID- 17854604 TI - A pill a day can improve survival in patients with advanced cirrhosis. PMID- 17854603 TI - Turning swords into plowshares: transglutaminase to detoxify gluten. PMID- 17854605 TI - The natural history and the staging of chronic hepatitis B: time for reevaluation of the virus-host relationship based on molecular virology and immunopathogenesis considerations? PMID- 17854607 TI - Biliary injury following laparoscopic cholecystectomy: why still a problem? PMID- 17854606 TI - BMP signaling in the intestine: cross-talk is key. PMID- 17854608 TI - The hepatitis C virus plot thickens: enter claudin-1. PMID- 17854609 TI - MLH1 germ-line epimutations: is there strong evidence of its inheritance? PMID- 17854610 TI - In"sight" into immune blindness: Helicobacter pylori-induced gastritis requires T cells primed in the small intestine Peyer's patches. PMID- 17854611 TI - Interleukin-23R Arg381Gln is associated with susceptibility to Crohn's disease but not with phenotype in an Italian population. PMID- 17854613 TI - Viremia profiles in hepatitis B virus carrier children with spontaneous e antigen seroconversion: a case of deja vu? PMID- 17854617 TI - Immediate dentin sealing supports delayed restoration placement. AB - STATEMENT OF PROBLEM: Immediate dentin sealing (IDS) is a new approach in indirect restorations. Dentin is sealed immediately following tooth preparation, prior to impression making. It is not known whether it is still possible to obtain an efficient bond between the resin-coated dentin and the restoration after 2 to 4 months of placement of provisional restorations. PURPOSE: The purpose of this study was to determine if there were differences in microtensile bond strength to human dentin using the IDS technique when comparing 2, 7, and 12 weeks of delay until restoration placement, using 2 different dentin bonding agents (DBAs). Previously published preliminary IDS data were included for comparison. MATERIAL AND METHODS: Fifty freshly extracted human molars were obtained and divided into 10 groups. A 3-step etch-and-rinse DBA (Optibond FL) and a 2-step self-etching DBA (SE Bond) were used. For each DBA, the control (C) specimens were prepared using a direct immediate bonding technique and composite restoration (Z100). Preparation of the other specimens used an indirect approach without dentin prebonding (delayed dentin sealing, DDS) or with immediate dentin sealing (IDS), immediately following preparation. IDS teeth had provisional restorations (Tempfil inlay) placed for 2 weeks (IDS-2W), 7 weeks (IDS-7W), or 12 weeks (IDS-12W) before restoration placement. All teeth were prepared for a nontrimming microtensile bond strength test (MTBS) 24 hours after definitive restoration with composite overlays (Z100). Ten to 11 beams (0.9 x 0.9 x 11 mm) from each tooth were selected for testing. MTBS data obtained from the 10 experimental groups were analyzed with a 2-way analysis of variance (ANOVA, dentin bonding system, and sequence of application) with each tooth (mean MTBS from the 10-11 beams) used as a single measurement. The Tukey HSD post hoc test was used to detect pairwise differences among experimental groups (alpha=.05). Fractured beams were also analyzed under stereoscopic microscope (x 30) and SEM. RESULTS: For both adhesives, the mean microtensile bond strengths of C and all IDS groups were not significantly different and exceeded 45 MPa. DDS groups exhibited lower bond strength than all others sequences (P<.001) with SE Bond at 1.81 MPa significantly lower (P=.026) than Optibond FL at 11.58 MPa. The highest mean microtensile bond strength values were found with Optibond FL at 7 weeks (66.59 MPa) and 12 weeks (59.11 MPa). These were significantly higher than SE Bond in the same conditions with values of 51.96 MPa and 45.76 MPa (P=.001 and P=.003), respectively. Failures in DDS groups were all interfacial and purely adhesive. Both C and IDS-2W groups demonstrated interfacial failure that was typically mixed with both areas of failed adhesive resin and areas of cohesively failed dentin while IDS-7W and IDS-12W failed consistently between the existing resin coating (used during IDS) and the overlaying composite resin. CONCLUSIONS: When preparing teeth for indirect bonded restorations, IDS with a 3-step etch rinse or a 2-step self-etching DBA (prior to impression making) results in microtensile bond strength similar to that obtained with a freshly placed adhesive. The bond strength is not affected by up to 12 weeks of elapsed time prior to placement of the definitive restoration. PMID- 17854618 TI - Coverage error of three conceptually different shade guide systems to vital unrestored dentition. AB - STATEMENT OF PROBLEM: It remains unclear which shade guide system is most representative of the shades found in the human dentition. PURPOSE: The purpose of this study was to determine and to compare the coverage errors (CEs) of 3 different shades in a selected population. MATERIAL AND METHODS: The coverage errors of the following shade guide systems were evaluated to determine which shade guide system is most effective in producing the best visual shade match: (1) Vita Lumin, (2) Chromascop, (3) Vitapan 3D Master, and (4) a combination of the 3 shade guide systems. The spectral reflectance values of the central one ninth (1-mm diameter) of each shade tab (without a backing) were measured with a spectroradiometer and an external light source at wavelengths from 380 nm to 780 nm at 2-nm intervals. All spectral reflectance measurements were made using 0 degree observer and 45-degree illumination and then converted to CIE values. The color values of 359 anterior teeth were measured with the same protocol. The CEs for each of the 359 anterior teeth for each shade guide system, and with all 3 shade guide systems, were determined and averaged. Repeated measure ANOVA was used to evaluate the mean minimum CEs within-subject (shade guide system) and between-subject (age) difference as well as the interaction between these variables (alpha=.05). Then, a post hoc multiple comparison was performed using the Tukey-Kramer test. RESULTS: A significant difference (P<.001) was found among the mean minimum CEs of the 3 shade guide systems and their combination, but not between age groups (P=.384). An interaction was found between shade guide systems and age (P<.001). The Tukey-Kramer test revealed that the mean minimum CEs for Vita Lumin (5.39 DeltaE) and Chromoscop (5.28 DeltaE) shade guide systems were not significantly different from each other. However, the combination of all 3 shade guide systems (3.69 DeltaE) and Vitapan 3D Master (3.93 DeltaE) were significantly different from the Vita Lumin and Chromoscop shade guide system. The rankings of the shade guide systems within each age group were similar between the age groups. CONCLUSIONS: The Vitapan 3D Master shade guide system resulted in the lowest coverage errors compared to the Vita Lumin or Chromascop shade guide systems. Coverage errors for the Vitapan 3D Master shade guide system did not differ significantly from the coverage errors when all 3 shade guide systems were combined. PMID- 17854619 TI - Fracture resistance of thermal cycled and endodontically treated premolars with adhesive restorations. AB - STATEMENT OF PROBLEM: Cavity preparations have routinely been associated with decreased fracture strength of restored teeth. PURPOSE: The purpose of this study was to evaluate the influence of endodontic treatment and thermal cycling on the fracture resistance of teeth restored with ceramic or composite resin inlay restorations. MATERIAL AND METHODS: One hundred sound, maxillary premolars were selected. Twenty intact teeth served as a control group. Eighty teeth were prepared with MOD cavity preparations; half of them were also endodontically treated. Inlay restorations were prepared with composite resin (Filtek Z250) or feldspathic ceramic (Vitadur Alpha). Half of the specimens for each group were submitted to thermal cycling (500 cycles, between 5 and 55 degrees C, dwell time of 30 seconds). The specimens were subjected to compressive axial loading using a steel ball. Data were analyzed using 3-way ANOVA and post hoc Tukey's test (alpha=.05). RESULTS: Except for those teeth restored with ceramic without endodontic treatment and thermal cycling, no other group achieved fracture strength similar to sound teeth. Ceramic and composite resin restorations provided similar resistance to fracture. There was a significant interaction between endodontic therapy and thermal cycling (P<.001). In the nonthermal cycled groups, endodontically treated teeth showed significantly lower fracture resistance (P<.001). All experimental groups had similar fracture strength when submitted to thermal cycling. CONCLUSIONS: Both restorative techniques provided similar fracture resistance. Endodontic treatment decreased the fracture resistance of nonthermal cycled specimens, while thermal cycling decreased the fracture resistance of nonendodontically treated specimens. PMID- 17854620 TI - The effect of resin cement film thickness on the pullout strength of a fiber reinforced post system. AB - STATEMENT OF PROBLEM: Debonding is a common cause of failure encountered with fiber posts and usually occurs along the post space-dentin adhesive interface. The ideal thickness of the resin cement needed to improve retentive bond strength is unknown. PURPOSE: The purpose of this study was to evaluate the effect of 4 different post-space diameters and related resin cement film thicknesses on the bond strength between fiber posts and root dentin. MATERIAL AND METHODS: Eighty human maxillary central incisors with similar root lengths were selected, sectioned at the cemento-enamel junction, and the roots were treated endodontically. The roots were divided into 4 groups (n=20), and the post spaces were prepared to a depth of 8 mm using 1 of 4 different drills with a different diameter: Torpan drill ISO 90 for the control group (D90); and Torpan Drill ISO 100 (D100), Torpan Drill ISO 120 (D120), or Enapost Drill ISO 140 (D140) for the 3 test groups. Quartz fiber posts (Endo Lightpost), 0.9 mm in apical diameter, were luted (Panavia 21) in each specimen after dentin bonding procedures. The specimens were then subjected to a pullout test using a universal testing machine at a crosshead speed of 1.0 mm/min, and the maximum force required to dislodge each post was recorded (N). Data were analyzed using 1-way ANOVA and Tukey multiple comparisons tests (a=.05). RESULTS: The mean bond strength values (SD) in N for the experimental groups D100 (181.7 (55.3)) and D120 (210.7 (55.0)) were higher (P=.036 and <.001, respectively) than that obtained for the D90 control group (138.5 (49.2)). The lowest mean value was recorded for the D140 group (91.1 (36.0)). All experimental groups showed significantly different results, when compared to the control group. A multiple comparison between experimental groups showed significant differences (P<.001). Only the comparison between D100 versus D120 was not significant. CONCLUSIONS: Data suggest that the resin cement film thickness influences the pullout strengths of fiber-reinforced posts. For the selected quartz fiber-reinforced post and resin luting cement, the highest bond strength values were not obtained when the thinnest cement layer was tested (D90) but when oversized post spaces were used (D100-D120). However, when the cement film thickness was too great (D140), the dislocation resistance of fiber reinforced posts was significantly decreased. PMID- 17854621 TI - Effect of metal type and surface treatment on in vitro tensile strength of copings cemented to minimally retentive preparations. AB - STATEMENT OF PROBLEM: Due to the potential lack of ideal preparation form, the type of alloy and its surface pretreatment may have clinically relevant correlations with the retentive strength of castings to minimally retentive preparations. PURPOSE: The purpose of this study was to evaluate the effect of alloy type and surface pretreatments of base and noble metal copings on their tensile strength to minimally retentive preparations. MATERIAL AND METHODS: Minimally retentive, standardized crown preparations were made on recently extracted human third molars (n=68). Noble (IPS d.SIGN 53) and base metal (Rexillium NBF) copings were fabricated. All copings received heat treatment for oxide formation. Three experimental groups were then developed for each metal type (groups ranging from 10 to 12 specimens each): oxide only, airborne-particle abraded, or metal-primed. Copings were cemented using a self-adhesive universal resin cement (RelyX Unicem) and were thermal cycled (500 cycles between 5 and 55 degrees C) and stored (24 hours, 37 degrees C) before debonding using a universal testing machine. Frequency of debond location was compared among specimen groups. A 2-way ANOVA was used to test for interaction between the metal type and surface treatment, and, if no significant interaction was found, to test the main effects for metal type and surface treatment (alpha=.05). A multinomial logit model using the likelihood ratio test was used to describe the effect of metal type and surface treatment on failure site location (alpha=.05). RESULTS: The 2-way ANOVA indicated no significant influence of any factor on debond load: metal type (P=.885), surface treatment (P=.555), or their interaction (P=.644). The multinomial logit statistical model showed that noble metals and metal primers significantly (P<.05) shifted debond failures to occur more frequently at the resin/tooth interface or within the tooth itself. CONCLUSIONS: Neither metal type nor surface pretreatment affected bond strength. However, alloy type and surface treatment affected site of debond location. (J Prosthet Dent 2007;98:199-207). PMID- 17854622 TI - Extrusion shear strength between an alumina-based ceramic and three different cements. AB - STATEMENT OF PROBLEM: Surface treatment is an essential step in bonding a ceramic to resin. Alumina ceramics are particularly difficult to prepare for adequate bonding to composite resin cements. PURPOSE: The purpose of this study was to evaluate the bond strength between a densely sintered alumina ceramic and bovine dentin with 2 adhesive resin cements and a resin-modified glass ionomer cement using an extrusion shear strength test. MATERIAL AND METHODS: Alumina cones (n=30), 4 mm in height, 3 mm in diameter at the small end, and with an 8-degree taper, were fabricated. Without any treatment, the cones were cemented in a standardized cavity in 2.5-mm-thick bovine dentin discs using 1 of 3 cement systems: Panavia F, RelyX ARC, or RelyX Luting. The cements were manipulated following the manufacturers' instructions. After 24 hours of storage at 37 degrees C, an extrusion shear test was performed in a universal testing machine at 0.5 mm/min until bonding failure. The data were analyzed using 1-way ANOVA and Tukey HSD test (alpha=.05). All fractured specimens were examined at x25 magnification and classified by fracture mode. Representative specimens were selected for SEM observation. RESULTS: The highest strength values were obtained with Panavia F, and they were significantly higher (P<.05) than each of the other 2 cements, which were not significantly different from each other. Panavia F resulted in predominantly mixed failure and RelyX ARC and RelyX Vitremer showed primarily adhesive failure. CONCLUSIONS: An MDP-containing adhesive system (Panavia F) provides better extrusion bond strength to a high-density alumina ceramic than a Bis-GMA resin luting agent system (RelyX ARC) or a resin-modified glass ionomer cement system (RelyX Luting). PMID- 17854623 TI - Influence of microwave disinfection on the dimensional stability of intact and relined acrylic resin denture bases. AB - STATEMENT OF PROBLEM: Microwave irradiation has been suggested as a method to disinfect denture bases. However, the effect of microwave heating on the dimensional stability of the relined denture bases is unknown. PURPOSE: The purpose of this study was to evaluate the dimensional stability of intact and relined acrylic resin denture bases after microwave disinfection. MATERIAL AND METHODS: A standard brass cast simulating an edentulous maxillary arch was machined and used to fabricate 2- and 4-mm-thick denture bases (n=200), which were processed with heat-polymerized acrylic resin (Lucitone 550). The 2-mm thick specimens (n=160) were relined with 2 mm of autopolymerizing resin (Tokuso Rebase Fast, Ufi Gel Hard, Kooliner, or New Truliner). Distances between 5 removable pins on the standard brass cast were measured with a Nikon optical comparator, and the area (mm) formed by the distance between 5 pins was calculated and served as baseline. During fabrication, the pins were transferred to the intaglio surface of the specimens. Differences between the baseline area and those subsequently determined for the specimens were used to calculate the percent dimensional changes. The intact and relined denture bases were divided into 4 groups (n=10) and evaluated after: polymerization (control group P); 1 cycle of microwave disinfection (MW); daily microwave disinfection for 7 days (control group MW7); water storage for 7 days (WS7). Microwave irradiation was performed for 6 minutes at 650 W. Data were analyzed using 2-way ANOVA followed by Tukey's test (alpha=.05). RESULTS: Intact specimens and those relined with Kooliner and New Truliner showed increased shrinkage after 1 (P=.05, .018, and .001, respectively) and 7 (P <.001, .003, and <.001, respectively) cycles of microwave disinfection. With the exception of specimens relined with Kooliner, intact specimens showed greater shrinkage than the relined specimens after 7 cycles of microwave disinfection. CONCLUSIONS: Microwave disinfection produced increased shrinkage of intact specimens and those relined with New Truliner and Kooliner. PMID- 17854624 TI - A new method for lateral pterygoid electromyographic electrode placement. AB - STATEMENT OF PROBLEM: Making electromyographic recordings of the lateral pterygoid muscle (LP) is difficult because of potential electrode damage to, for example, the maxillary artery and long buccal nerve, and because of pain and reduced jaw mobility characteristic of many orofacial pain patients. PURPOSE: The purpose of this study was to develop a reliable intraoral placement technique for the inferior head of the lateral pterygoid (IHLP) that minimizes jaw displacement. MATERIAL AND METHODS: In 2 dried skulls and 7 human cadavers, it was estimated that, with the mandible in an ipsilateral closed position, a straight needle could be used to position fine-wire electrodes into the midportion of IHLP by inserting the needle through the mucosa adjacent to the distal root of the maxillary second molar, towards the external auditory meatus and parallel to the buccal alveolar bone of the maxilla. The needle avoided the maxillary artery and long buccal nerve. Using this approach in 5 adults, 2 fine wire electrodes were placed into the IHLP. Placement was verified by computer tomography (CT) and electromyography. RESULTS: In all subjects, the ideal insertion depth to place the electrodes in the middle of IHLP was 29 mm. CONCLUSIONS: This technique is a reliable method for IHLP electrode placement for patients with impaired jaw function, minimizing risk of damage to major structures. PMID- 17854625 TI - An expedited technique for remaking a single complete denture for an edentulous patient. AB - Traditional techniques for fabricating complete dentures commonly require 5 visits. Reduction of the number of visits and chair time for complete denture fabrication would be welcomed by dentists and patients. This article describes and illustrates clinical and laboratory procedures for fabricating a new denture for a patient with an existing complete denture. The procedure can be completed in 3 to 4 visits. PMID- 17854626 TI - Use of a vacuum-formed plastic sheet to aid in transferring and bonding metal splints. AB - Mobile teeth with compromised periodontal support may shift from their unstressed position during clinical splinting procedures and be stabilized in an incorrect position, resulting in occlusal interferences and unnecessary adjustment. A technique is presented that can be helpful to splint mobile teeth with a metal device. Using a vacuum or pressure device to create a mold using a cast transfers the splint intraorally for bonding. This thermoplastic sheet maintains mobile teeth in the desired position during the splinting procedure. PMID- 17854627 TI - Telescoping implant prostheses with intraoral luted galvano mesostructures to improve passive fit. AB - A passive fit of implant-supported prostheses seems to be a prerequisite for the prevention of mechanical complications. As a certain level of distortion of multiimplant screw-retained restorations seems inevitable, cementation of implant frameworks has been advocated to compensate for discrepancies. However, cement retained prostheses have disadvantages, including lack of retrievability. This article describes a technique for the fabrication of telescopic, metal-acrylic resin, implant-supported complete dentures. Precise fit is achieved by intraoral luting of telescopic galvano mesostructures to the framework. PMID- 17854628 TI - A modified one-step putty-wash impression technique. PMID- 17854654 TI - Structural basis of effector regulation and signal termination in heterotrimeric Galpha proteins. AB - This chapter addresses, from a molecular structural perspective gained from examination of x-ray crystallographic and biochemical data, the mechanisms by which GTP-bound Galpha subunits of heterotrimeric G proteins recognize and regulate effectors. The mechanism of GTP hydrolysis by Galpha and rate acceleration by GAPs are also considered. The effector recognition site in all Galpha homologues is formed almost entirely of the residues extending from the C terminal half of alpha2 (Switch II) together with the alpha3 helix and its junction with the beta5 strand. Effector binding does not induce substantial changes in the structure of Galpha*GTP. Effectors are structurally diverse. Different effectors may recognize distinct subsets of effector-binding residues of the same Galpha protein. Specificity may also be conferred by differences in the main chain conformation of effector-binding regions of Galpha subunits. Several Galpha regulatory mechanisms are operative. In the regulation of GMP phospodiesterase, Galphat sequesters an inhibitory subunit. Galphas is an allosteric activator and inhibitor of adenylyl cyclase, and Galphai is an allosteric inhibitor. Galphaq does not appear to regulate GRK, but is rather sequestered by it. GTP hydrolysis terminates the signaling state of Galpha. The binding energy of GTP that is used to stabilize the Galpha:effector complex is dissipated in this reaction. Chemical steps of GTP hydrolysis, specifically, formation of a dissociative transition state, is rate limiting in Ras, a model G protein GTPase, even in the presence of a GAP; however, the energy of enzyme reorganization to produce a catalytically active conformation appears to be substantial. It is possible that the collapse of the switch regions, associated with Galpha deactivation, also encounters a kinetic barrier, and is coupled to product (Pi) release or an event preceding formation of the GDP*Pi complex. Evidence for a catalytic intermediate, possibly metaphosphate, is discussed. Galpha GAPs, whether exogenous proteins or effector-linked domains, bind to a discrete locus of Galpha that is composed of Switch I and the N-terminus of Switch II. This site is immediately adjacent to, but does not substantially overlap, the Galpha effector binding site. Interactions of effectors and exogenous GAPs with Galpha proteins can be synergistic or antagonistic, mediated by allosteric interactions among the three molecules. Unlike GAPs for small GTPases, Galpha GAPs supply no catalytic residues, but rather appear to reduce the activation energy for catalytic activation of the Galpha catalytic site. PMID- 17854655 TI - How do receptors activate G proteins? AB - Heterotrimeric G proteins couple the activation of heptahelical receptors at the cell surface to the intracellular signaling cascades that mediate the physiological responses to extracellular stimuli. G proteins are molecular switches that are activated by receptor-catalyzed GTP for GDP exchange on the G protein alpha subunit, which is the rate-limiting step in the activation of all downstream signaling. Despite the important biological role of the receptor-G protein interaction, relatively little is known about the structure of the complex and how it leads to nucleotide exchange. This chapter will describe what is known about receptor and G protein structure and outline a strategy for assembling the current data into improved models for the receptor-G protein complex that will hopefully answer the question as to how receptors flip the G protein switch. PMID- 17854656 TI - Some mechanistic insights into GPCR activation from detergent-solubilized ternary complexes on beads. AB - The binding of full and partial agonist ligands (L) to G protein-coupled receptors (GPCRs) initiates the formation of ternary complexes with G proteins [ligand-receptor-G protein (LRG) complexes]. Cyclic ternary complex models are required to account for the thermodynamically plausible complexes. It has recently become possible to assemble solubilized formyl peptide receptor (FPR) and beta(2)-adrenergic receptor (beta(2)AR) ternary complexes for flow cytometric bead-based assays. In these systems, soluble ternary complex formation of the receptors with G proteins allows direct quantitative measurements which can be analyzed in terms of three-dimensional concentrations (molarity). In contrast to the difficulty of analyzing comparable measurements in two-dimensional membrane systems, the output of these flow cytometric experiments can be analyzed via ternary complex simulations in which all of the parameters can be estimated. An outcome from such analysis yielded lower affinity for soluble ternary complex assembly by partial agonists compared with full agonists for the beta(2)AR. In the four-sided ternary complex model, this behavior is consistent with distinct ligand-induced conformational states for full and partial agonists. Rapid mix flow cytometry is used to analyze the subsecond dynamics of guanine nucleotide mediated ternary complex disassembly. The modular breakup of ternary complex components is highlighted by the finding that the fastest step involves the departure of the ligand-activated GPCR from the intact G protein heterotrimer. The data also show that, under these experimental conditions, G protein subunit dissociation does not occur within the time frame relevant to signaling. The data and concepts are discussed in the context of a review of current literature on signaling mechanism based on structural and spectroscopic (FRET) studies of ternary complex components. PMID- 17854657 TI - Activation of G protein-coupled receptors. AB - G protein-coupled receptors (GPCRs) mediate responses to hormones and neurotransmitters, as well as the senses of sight, smell, and taste. These remarkably versatile signaling molecules respond to structurally diverse ligands. Many GPCRs couple to multiple G protein subtypes, and several have been shown to activate G protein-independent signaling pathways. Drugs acting on GPCRs exhibit efficacy profiles that may differ for different signaling cascades. The functional plasticity exhibited by GPCRs can be attributed to structural flexibility and the existence of multiple ligand-specific conformational states. This chapter will review our current understanding of the mechanism by which agonists bind and activate GPCRs. PMID- 17854658 TI - Kinetic analysis of G protein-coupled receptor signaling using fluorescence resonance energy transfer in living cells. AB - We describe and review methods for the kinetic analysis of G protein-coupled receptor (GPCR) activation and signaling that are based on optical methods. In particular, we describe the use of fluorescence resonance energy transfer (FRET) as a means of analyzing conformational changes within a single protein (for example a receptor) or between subunits of a protein complex (such as a G protein heterotrimer) and finally between distinct proteins (such as a receptor and a G protein). These methods allow the analysis of signaling kinetics in intact cells with proteins that retain their essential functional properties. They have produced a number of unexpected results: fast receptor activation kinetics in the millisecond range, similarly fast kinetics for receptor-G protein interactions, but much slower activation kinetics for G protein activation. PMID- 17854659 TI - Regulation of Rho guanine nucleotide exchange factors by G proteins. AB - Monomeric Rho GTPases regulate cellular dynamics through remodeling of the cytoskeleton, modulation of immediate signaling pathways, and longer-term regulation of gene transcription. One family of guanine nucleotide exchange factors for Rho proteins (RhoGEFs) provides a direct pathway for regulation of RhoA by cell surface receptors coupled to heterotrimeric G proteins. Some of these RhoGEFs also contain RGS domains that can attenuate signaling by the G(12) and G(13) proteins. The regulation provided by these RhoGEFs is defined by their selective regulation by specific G proteins, phosphorylation by kinases, and potential localization with signaling partners. Evidence of their physiological importance is derived from gene knockouts in Drosophila and mice. Current understanding of the basic regulatory mechanisms of these RhoGEFs is discussed. An overview of identified interactions with other signaling proteins suggests the growing spectrum of their involvement in numerous signaling pathways. PMID- 17854660 TI - Cytogenetic, morphological, and immunophenotypic patterns in Omani patients with de novo acute myeloid leukemia. AB - Chromosome aberrations observed at diagnosis are considered to be the most valuable prognostic factors in acute myeloid leukemia (AML). Some specific aberrations vary in frequency among different geographical areas and ethnic groups. There are only limited studies on the role of such variability in AML patients. Here, we report the results of a cytogenetic study on 63 ethnic Omani patients with de novo AML: 18 children ( 0.05) and 30 of 56 colon carcinoma patients (53.6%; P < 0.05) using antigen anticor interaction methods. Comparing the frequencies of the two separate population control groups, the APC I1307K allele is associated with an estimated relative risk of 1.9 for colorectal neoplasia. Furthermore, APC I1307K carriers had greater numbers of adenomas and colorectal cancers per patient than noncarriers. The conclusion is that the APC I1307K variant leads to increased adenoma formation and colorectal cancer. The estimated relative risk for carriers may justify specific clinical screening for Turkish people expected to harbor this allele, and genetic testing in the long term may significantly promote colorectal cancer prevention in this population. PMID- 17854662 TI - HMGA2 expression in a canine model of prostate cancer. AB - Prostate cancer is the most prevalent cancer in western countries, being the third leading cause of male cancer death. To check its possible significance as a prognostic marker, allowing a better prognosis of the tumor, we analyzed the high mobility group protein-A2 gene (HMGA2) expression level because HMGA2 overexpression has been shown to correlate with the malignant potential of various neoplasias. Aside from man, the dog is the only mammalian species that shows spontaneously occurring prostate carcinoma with striking similarities to prostate cancer growth and progression in man, making it an adequate animal model for this neoplasia. We used real-time quantitative reverse-transcription polymerase chain reaction for HMGA2 expression analyses in a subset of canine prostate tissue samples. Our investigations reveal that HMGA2 expression levels in all carcinomas were higher than those of any of the nonmalignant tissues. Thus, canine prostate cancer represents a spontaneously occurring model to test therapeutic effects resulting from reduced expression of HMGA2. PMID- 17854663 TI - TP53 codon 72 polymorphism, p53 expression, and 1p/19q status in oligodendroglial tumors. AB - The functional single-nucleotide polymorphism (SNP) in codon 72 of TP53 has been shown to be both a risk factor and a prognostic biomarker in various cancers. Such results were also reported in brain tumors, notably in astrocytomas. This SNP has never been precisely investigated in oligodendroglial tumors. We retrospectively analyzed blood samples of 275 oligodendroglial tumor patients for the TP53 codon 72 polymorphism and compared them with a series of 144 healthy controls. Arg/Arg, Arg/Pro, and Pro/Pro genotypes were found in 54.2 versus 60.4%, 39.3 versus 34.0%, and 7.3 versus 5.6% of patients and controls, respectively. This suggests no association between oligodendroglial tumors and the SNP in codon 72 of TP53. Similarly, no correlation was found among the TP53 codon 72 polymorphism and prognosis, p53 expression, and chromosomes 1p and 19q status. PMID- 17854664 TI - C/EBPbeta suppression by interruption of CUGBP1 resulting from a complex rearrangement of MLL. AB - Translocations involving the mixed-lineage leukemia gene (MLL) confer a poor prognosis in acute leukemias. In t(1;11)(q21;q23), MLL is fused reciprocally with AF1q. Here we describe a t(1;11)(q21;q23) with a secondary event involving insertion of the telomeric portion of MLL into the p arm of chromosome 11 (11p11). We show that this latter event interrupts the CUG triplet repeat binding protein-1 (CUGBP1) gene, a translational enhancer of C/EBPbeta. We then showed that these cells have reduced expression of CUGBP1 and C/EBPbeta when compared to other AML blasts. This is the first report to describe insertional disruption of the CUGBP1 gene and to suggest a role for the CUGBP1-C/EBPbeta pathway in leukemogenesis. PMID- 17854665 TI - HMGA2 overexpression in polycythemia vera with t(12;21)(q14;q22). AB - Chromosomal translocations involving the 12q14 band are rarely detected in hematological disorders, and are usually correlated with HMGA2 gene expression. HMGA2 is highly expressed during embryonic cell growth and differentiation, and regulates transcription and chromatin organization, but is rarely detectable in adult tissues. We describe a case of polycythemia vera with a t(12;21)(q14;q22). The 12q14 breakpoint was characterized by fluorescence in situ hybridization analysis using the bacterial artificial chromosome RP11-366L20 containing 3' sequences of the HMGA2 gene. Qualitative and quantitative polymerase chain reaction showed the presence of high levels of HMGA2 gene expression, which were temporarily reduced with hydroxyurea therapy. The present case confirms that involvement of the 12q14 band may be associated with HMGA2 overexpression in chronic Philadelphia chromosome-negative myeloproliferative disease, regardless of the partner chromosome involved in the translocation. Such overexpression may contribute to the pathogenesis of the disease, which otherwise of itself shows a favorable and stable course. PMID- 17854666 TI - Two novel translocations disrupt the RUNX1 gene in acute myeloid leukemia. AB - Translocations involving 21q22 are commonly observed in both de novo and therapy related acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). They often result in the disruption of RUNX1 and give rise to fusion genes consisting of RUNX1 and different partner genes, which contribute to leukemogenesis. To date, at least 21 such translocations are known from the literature. Here we report two novel translocations involving the RUNX1 gene: t(1;21)(q12;q22) in a 53-year-old woman with AML-M5b and t(11;21)(q13;q22) in a 65-year-old man with AML-M2. The abnormalities revealed by R-banding karyotypic analysis were confirmed with interphase and metaphase fluorescence in situ hybridization (FISH), chromosome painting, and M-FISH. PMID- 17854667 TI - Diverse molecular pattern in a bihemispheric glioblastoma (butterfly glioma) in a 16-year-old boy. AB - Glioblastoma multiforme (GBM), the most common malignant brain tumor of adults, is relatively rare in children. In a GBM affecting a 16-year-old boy, the tumor spread across the corpus callosum (butterfly glioma). This type of bilateral hemispheric growth has previously been thought to result from spread along the white matter tracts. Two samples obtained from opposite sides of the same tumor were analyzed comprehensively for loss of heterozygosity (LOH) and microsatellite instability (MSI). Amplification of EGFR and MDM2 was studied by means of multiplex polymerase chain reaction. Exons 5, 6, 7, and 8 of TP53 were screened for mutations by sequencing. In neither specimen were molecular alterations found in the EGFR, MDM2, or TP53 genes. The specimen obtained from the right hemisphere exhibited a high level of MSI and LOH in chromosome arms 5q, 9p, and 13q. The specimen from the left hemisphere exhibited LOH in chromosome arms 3p, 5q, 9p, 9q, 10p, 10q, and 13q. Here we propose four plausible hypothetical scenarios underlying the tumorigenesis of this GBM. PMID- 17854668 TI - Cellular angiofibroma is genetically similar to spindle cell lipoma: a case report. AB - Cellular angiofibroma is a benign mesenchymal neoplasm of female and male genital tract composed of prominent vasculature and stromal spindle cells, often with admixture of adipose tissue. The tumor has histomorphologic similarities to angiomyofibroblastoma and spindle cell lipoma. Herein we describe a tumor arising in the perineal region of a 60-year-old man with morphological and immunohistochemical features of cellular angiofibroma and showing cytogenetic characteristics similar to spindle cell lipoma. To our knowledge, this is the first report of cytogenetic changes in cellular angiofibroma. The genetic overlap of these entities supports their origin from the same mesenchymal stem cell. PMID- 17854669 TI - Relapsed acute myelogenous leukemia occurring after 18 years with recurrent novel chromosomal abnormality t(18;22)(q23;q11.2). AB - A 22-year-old woman presented with lymphadenopathy in a similar manner as she had presented at age 4. At age 4, she was diagnosed with acute myelogenous leukemia (AML) with t(18;22)(q23;q11.2) and received chemotherapy until age 6 under a pediatric study protocol. At age 22, a lymph node biopsy confirmed granulocytic sarcoma, and a bone marrow aspirate showed increased myeloblasts with no dysplasia. Cytogenetic analyses of the lymph node and the bone marrow were positive for t(18;22)(q23;q11.2). The patient was treated for relapsed AML and at writing had been disease-free for 9 months. Translocation between chromosomes 18 and 22 has been reported in indolent lymphoproliferative disorders, but not in AML. Although we do not know the precise molecular etiology of this leukemia, the uncommon presentation for AML and late relapse with the same chromosomal abnormality may indicate a causal relationship between this novel chromosomal abnormality and the AML. This observation also suggests the possible presence of dormant stem cells containing the chromosomal abnormality in this particular patient. PMID- 17854670 TI - Myxoinflammatory fibroblastic sarcoma showing t(2;6)(q31;p21.3) as a sole cytogenetic abnormality. AB - Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare, low-grade sarcoma characterized by distinctive, large, and bizarre Reed--Sternberg--like cells associated with an intense inflammatory infiltrate. The biology of MIFS is still poorly understood, and only two previous cases had been studied cytogenetically. In the present case, analysis of MIFS in the foot of a 53-year-old man revealed the chromosome translocation t(2;6)(q31;p21.3) as the only cytogenetic abnormality. This finding is distinct from the two cases previously reported. Additional studies are needed to verify whether any of these chromosome rearrangements are involved recurrently in MIFS. PMID- 17854671 TI - Translocation (4;11)(p12;q23) with rearrangement of FRYL and MLL in therapy related acute myeloid leukemia. AB - Reciprocal chromosomal translocations involving the MLL gene at chromosome region 11q23 are recurring cytogenetic abnormalities in both de novo and therapy-related acute myeloid leukemia (AML) and in acute lymphoblastic leukemia. We report a t(4;11)(p12;q23) with rearrangement of MLL and FRYL (also known as AF4p12), a human homolog to the furry gene of Drosophila, in an adult patient with therapy related AML after fludarabine and rituximab therapy for small lymphocytic lymphoma and radiation therapy for breast carcinoma. To our knowledge, t(4;11)(p12;q23) has been reported in two previous patients, and MLL and FRYL rearrangement was demonstrated in one of them. Both of the previous patients had therapy-related leukemias after exposure to topoisomerase II inhibitors, whereas our patient had received cytotoxic therapy that did not include a topoisomerase II inhibitor. Thus, t(4;11)(p12;q23) with MLL and FRYL involvement represents a new recurring 11q23 translocation, to date seen only in therapy-related acute leukemias. PMID- 17854672 TI - Leiomyoma of the urinary bladder: a cytogenetic study of a case. AB - We report the first case of a leiomyoma of the urinary bladder studied by cytogenetics. In comparison with cytogenetic changes of leiomyomas of other sites, the karyotype of the tumor was unusual: 47,XX,+7/89 approximately 93,XXXX, 1,+7,+7,add(12)(q23.4),+add(12)(q23.4),-18,-21,+idic(21)(p11.2),-22. PMID- 17854673 TI - The CYP3A4 *1B polymorphism and prostate cancer susceptibility in a Portuguese population. AB - Testosterone exposure has been implicated in prostate carcinogenesis, and genes that alter its metabolism, such as CYP3A4, have been associated with prostate cancer susceptibility. The aim of our study was to assess the relationship between the CYP3A4 *1B polymorphism and its possible role in the development of prostate cancer. DNA samples obtained from the peripheral blood cells of 414 individuals diagnosed with prostate cancer and 337 healthy male donors were used in this case-control study. The CYP3A4*1B polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism methodology. We found no statistically significant differences in the distribution of the CYP3A4*1B genotypes between cases and controls (P = 0.470; odds ratio = 1.191; 95% confidence interval=0.740-1.918), as well as after the stratification of our analysis, according to important clinicopathologic parameters of prostate cancer. Our results suggest that the CYP3A4*1B polymorphism is not associated with prostate cancer risk within the Portuguese population. PMID- 17854674 TI - Can bladder adenocarcinomas be distinguished from schistosomiasis-associated bladder cancers by using array comparative genomic hybridization analysis? AB - Bladder cancer is the most common malignancy in many tropical and subtropical areas, correlating well with the endemicity of schistostomiasis. The majority of schistostomiasis-associated (SA) bladder cancers are squamous cell cancers, whereas the majority of non-SA cases in the Western world are transitional cell cancers, suggesting different carcinogenetic mechanisms. Approximately 6% of SA and 1% of non-SA cases are adenocarcinomas. To achieve fine-resolution information of DNA copy number changes in SA adenocarcinomas, 10 tumor samples were analyzed on an oligonucleotide-based CGH array. The frequency of aberrations ranged from 2 to 17, with an average of 10 alterations per sample. The most frequently gained regions were 20q and 8q (in 70 and 60% of the cases, respectively), whereas the most frequently lost regions were 5q and 8p (both in 40% of the cases). In addition, six regions of amplification were found in three samples, containing both well characterized and novel regions. Comparison of the DNA copy number profiles to previously reported profiles of SA transitional cell carcinoma and squamous cell carcinoma revealed similarities (e.g., gains at 5p and 8q), as well as differences (e.g., TCC- and SCC-associated losses at 18p and 20p, and adenocarcinoma-associated gains at 20q). The results suggest that although SA cancers share genetic features, there also exist histology-specific regions of gain and loss. PMID- 17854675 TI - t(5;12)(q13;p13) in acute myeloid leukemia with preceding granulocytic sarcoma. AB - A 56-year-old woman was brought to the emergency room with gum swelling and pain. Biopsy of the gingiva revealed sheet-like proliferation of myeloperoxidase and CD45-positive large cells, and she was diagnosed with granulocytic sarcoma. Two years later, bone marrow involvement of granulocytic sarcoma was suspected. Her chromosome study repeatedly revealed a 46,XX,t(5;12)(q13;p13) karyotype. Case reports of t(5;12)(q13;p13) are extremely rare in the literature. To our knowledge, this is the first report of t(5;12)(q13;p13) in a patient with acute myelogenous leukemia with preceding granulocytic sarcoma. PMID- 17854677 TI - A novel t(12;15)(q22;q13) in a patient with acute monoblastic leukemia. PMID- 17854676 TI - Presenting features of 201 children with acute lymphoblastic leukemia: comparison according to presence or absence of ETV6/RUNX1 rearrangement. PMID- 17854678 TI - Concomitant appearance of trisomy 8 and isochromosome 17q in a Philadelphia positive clone in a patient with chronic myeloid leukemia in chronic phase: an alarm for changing therapeutic strategy. PMID- 17854706 TI - Lipid peroxidation-induced DNA damage in cancer-prone inflammatory diseases: a review of published adduct types and levels in humans. AB - Persistent oxidative stress and excess lipid peroxidation (LPO), induced by inflammatory processes, impaired metal storage, and/or dietary imbalance, cause accumulations and massive DNA damage. This massive DNA damage, along with deregulation of cell homeostasis, leads to malignant diseases. Reactive aldehydes produced by LPO, such as 4-hydroxy-2-nonenal, malondialdehyde, acrolein, and crotonaldehyde, react directly with DNA bases or generate bifunctional intermediates which form exocyclic DNA adducts. Modification of DNA bases by these electrophiles, yielding promutagenic exocyclic adducts, is thought to contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. Ultrasensitive detection methods have facilitated studies of the concentrations of promutagenic DNA adducts in human tissues, white blood cells, and urine, where they are excreted as modified nucleosides and bases. Thus, immunoaffinity-(32)P-postlabeling, high-performance liquid chromatography electrochemical detection, gas chromatography-mass spectrometry, liquid chromatography-tandem mass spectrometry, immunoslotblot assay, and immunohistochemistry have made it possible to detect background concentrations of adducts arising from endogenous LPO products in vivo and studies of their role in carcinogenesis. These background adduct levels in asymptomatic human tissues occur in the order of 1 adduct/10(8) and in organs affected by cancer-prone inflammatory diseases these can be 1 or 2 orders of magnitude higher. In this review, we critically discuss the accuracy of the available methods and their validation and summarize studies in which measurement of exocyclic adducts suggested new mechanisms of cancer causation, providing potential biomarkers for cancer risk assessment in humans with cancer-prone diseases. PMID- 17854705 TI - Thiol oxidation in signaling and response to stress: detection and quantification of physiological and pathophysiological thiol modifications. AB - Cysteine thiol modifications are increasingly recognized to occur under both physiological and pathophysiological conditions, making their accurate detection, identification, and quantification of growing importance. Among free cysteines, the bulk of modifications occurs on a subset of cysteines that are more reactive. These exist as thiolate anions at physiological pH because of their surrounding electrostatic environment. Reagents with iodoacetamide-active groups can be used to selectively label these reactive thiols with a high degree of selectivity. Thiol adducts can be detected by the failure to label with iodoacetamide or other reagents; restoration of labeling by specific reducing agents (e.g., ascorbate or glutaredoxin) can be used to detect reversible S-nitroso and S-glutathione adducts. These adducts also may be detected with radiolabels and antibodies. S Glutathiolation in response to physiological stimuli may be detected in cells and tissues with glutathione ester labeled with biotin. Mass spectrometry can identify thiol modifications with precision, and with isotope-coded affinity tags, used to quantify modification of specific thiols. Combinations of these methods increase sensitivity and specificity, and enable quantification and precise identification of thiol modifications that occur under physiological and pathological conditions. PMID- 17854707 TI - So many choices, so what's a consumer to do?: A commentary on "Effect of chromium niacinate and chromium picolinate supplementation on lipid peroxidation, TNF alpha, IL-6, CRP, glycated hemoglobin, triglycerides, and cholesterol levels in blood of streptozotocin-treated diabetic rats". PMID- 17854708 TI - Effect of chromium niacinate and chromium picolinate supplementation on lipid peroxidation, TNF-alpha, IL-6, CRP, glycated hemoglobin, triglycerides, and cholesterol levels in blood of streptozotocin-treated diabetic rats. AB - Chromium (Cr(3+)) supplementation facilitates normal protein, fat, and carbohydrate metabolism, and is widely used by the public in many countries. This study examined the effect of chromium niacinate (Cr-N) or chromium picolinate (Cr P) supplementation on lipid peroxidation (LP), TNF-alpha, IL-6, C-reactive protein (CRP), glycosylated hemoglobin (HbA(1)), cholesterol, and triglycerides (TG) in diabetic rats. Diabetes (D) was induced in Sprague-Dawley rats by streptozotocin (STZ) (ip, 65 mg/kg BW). Control buffer, Cr-N, or Cr-P (400 microg Cr/kg BW) was administered by gavages daily for 7 weeks. Blood was collected by heart puncture using light anesthesia. Diabetes caused a significant increase in blood levels of TNF-alpha, IL-6, glucose, HbA(1), cholesterol, TG, and LP. Compared with D, Cr-N supplementation lowered the blood levels of TNF-alpha (P=0.04), IL-6 (P=0.02), CRP (P=0.02), LP (P=0.01), HbA(1) (P=0.02), TG (P=0.04), and cholesterol (P=0.04). Compared with D, Cr-P supplementation showed a decrease in TNF-alpha (P=0.02), IL-6 (P=0.02), and LP (P=0.01). Chromium niacinate lowers blood levels of proinflammatory cytokines (TNF-alpha, IL-6, CRP), oxidative stress, and lipids levels in diabetic rats, and appears to be a more effective form of Cr(3+) supplementation. This study suggests that Cr(3+) supplementation can lower the risk of vascular inflammation in diabetes. PMID- 17854710 TI - DNA damage, superoxide, and mutant K-ras in human lung adenocarcinoma cells. AB - DNA single-strand breaks (quantitative comet assay) were assessed to indicate ongoing genetic instability in a panel of human lung adenocarcinoma cell lines. Of these, 19/20 showed more DNA damage than a nontransformed cell line from human peripheral lung epithelium, HPL1D. DNA damage was significantly greater in those derived from pleural effusates vs those from lymph node metastases. DNA strand breaks correlated positively with superoxide (nitroblue tetrazolium reduction assay), and negatively with amount of OGG1, a repair enzyme for oxidative DNA damage. Levels of CuZn superoxide dismutase varied moderately among the lines and did not correlate with other parameters. A role for mutant K-ras through generation of reactive oxygen species was examined. Cells with mutant K-ras had significantly lower amounts of manganese superoxide dismutase (MnSOD) vs those with wild-type K-ras, but MnSOD protein correlated positively with superoxide levels. In a subset of cell lines with similar levels of MnSOD, comparable to those in HPL1D cells, K-ras activity correlated positively with levels of both superoxide and DNA strand breaks. These results suggest that persistent DNA damage in some lung adenocarcinoma cells may be caused by superoxide resulting from mutant K-ras activity, and that OGG1 is important for prevention of this damage. PMID- 17854709 TI - Mechanism of the cytotoxicity of the diazoparaquinone antitumor antibiotic kinamycin F. AB - The bacterial metabolite kinamycin F, which is being investigated as a potent antitumor agent, contains an unusual and potentially reactive diazo group, a paraquinone, and a phenol functional group. Kinamycin F reacted with glutathione (GSH) in a complex series of reactions which suggested that kinamycin F may have its cytotoxicity modulated by GSH. Consistent with this idea, 2-oxo-4 thiazolidinecarboxylic acid treatment to increase cellular GSH levels and buthionine sulfoximine treatment to decrease GSH levels resulted in decreased and increased kinamycin F cytotoxicity, respectively, in K562 leukemia cells. Kinamycin F weakly bound to DNA and induced DNA damage in K562 cells that was independent of GSH levels. The GSH-promoted DNA nicking induced by kinamycin F in vitro was attenuated by deferoxamine, dimethyl sulfoxide, and catalase, which indicated that DNA damage initiated by this agent occurred in an iron-, hydrogen peroxide-, and hydroxyl-radical-dependent manner. Electron paramagnetic resonance spectroscopy experiments showed that the GSH/kinamycin F system produced a semiquinone free radical and that the hydrogen peroxide/peroxidase/kinamycin F system generated a phenoxyl free radical. In conclusion, the results indicated that kinamycin F cytotoxicity may be due to reductive and/or peroxidative activation to produce DNA-and protein-damaging species. PMID- 17854711 TI - Inhibition of free radical-induced erythrocyte hemolysis by 2-O-substituted ascorbic acid derivatives. AB - Inhibitory effects of 2-O-substituted ascorbic acid derivatives, ascorbic acid 2 glucoside (AA-2G), ascorbic acid 2-phosphate (AA-2P), and ascorbic acid 2-sulfate (AA-2S), on 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced oxidative hemolysis of sheep erythrocytes were studied and were compared with those of ascorbic acid (AA) and other antioxidants. The order of the inhibition efficiency was AA-2S> or =Trolox=uric acid> or =AA-2P> or =AA-2G=AA>glutathione. Although the reactivity of the AA derivatives against AAPH-derived peroxyl radical (ROO(*)) was much lower than that of AA, the derivatives exerted equal or more potent protective effects on AAPH-induced hemolysis and membrane protein oxidation. In addition, the AA derivatives were found to react per se with ROO(*), not via AA as an intermediate. These findings suggest that secondary reactions between the AA derivative radical and ROO(*) play a part in hemolysis inhibition. Delayed addition of the AA derivatives after AAPH-induced oxidation of erythrocytes had already proceeded showed weaker inhibition of hemolysis compared to that of AA. These results suggest that the AA derivatives per se act as biologically effective antioxidants under moderate oxidative stress and that AA-2G and AA-2P may be able to act under severe oxidative stress after enzymatic conversion to AA in vivo. PMID- 17854712 TI - Vitamin C modulation of H2O2-induced damage and iron homeostasis in human cells. AB - Vitamin C (ascorbic acid, AA) is an important antioxidant in human plasma. It is clear, however, that AA has other important, nonantioxidant roles in cells. Of particular interest is its involvement in iron metabolism, since AA enhances dietary iron absorption, increases the activity of Fe(2+)-dependent cellular enzymes, promotes Fenton reactions in vitro, and was reported to have deleterious effects in individuals with iron overload. Nevertheless, the ability of AA to modulate iron metabolism and enhance iron-dependent damage in cells, tissues, and organisms has not been fully elucidated. Here we investigated the effect of AA on iron-mediated oxidative stress in normal human fibroblasts. Incubation with physiologically relevant concentrations of AA was not harmful but sensitised cells toward H(2)O(2)-induced, iron-dependent DNA strand breakage and cell death. We also report that AA increased the levels of intracellular catalytic iron and concomitantly modulated the expression of two well-established iron-regulated genes, ferritin and transferrin receptor. In summary, we present evidence of a novel, nonantioxidant role of AA in human cells, where it increases iron availability and enhances ROS-mediated, iron-dependent damage. We suggest that AA may exacerbate the deleterious effects of metals in vivo and promote normal tissue injury in situations associated with elevated ROS production. PMID- 17854713 TI - Ozone enhancement of lower airway allergic inflammation is prevented by gamma tocopherol. AB - Ozone is a commonly encountered environmental oxidant which has been linked to asthma exacerbation in epidemiological studies. Ozone induces airway inflammation and enhances response to inhaled allergen. It has been suggested that antioxidant therapy may minimize the adverse effects of ozone in asthma. We have previously shown that the antioxidant gamma-tocopherol (gammaT), an isoform of vitamin E, also has anti-inflammatory effects. We employed a Brown Norway rat model of ozone enhanced allergic responses to test the therapeutic effects of gammaT on O(3) induced airway inflammation. Ovalbumin (OVA)-sensitized rats were intranasally challenged with 0 or 0.5% OVA on Days 1 and 2, and exposed to 0 or 1 ppm ozone (8 h/day) on Days 4 and 5. Rats were also given 0 or 100 mg/kg gammaT on Days 2 through 5. Pulmonary tissue and bronchoalveolar lavage fluid (BALF) were collected on Day 6. OVA challenge caused increased total cells (267% increase) and eosinophils (4000%) in BALF that was unaffected by ozone exposure. Morphometric evaluation of lung tissue revealed increases in intraepithelial mucosubstances (IM) (300%) and subepithelial eosinophils (400%) in main axial airways. Ozone exposure of allergic rats enhanced IM increases in proximal axial airways (200%), induced cys-leukotrienes, MCP-1, and IL-6 production in BALF, and upregulated expression of IL-5 and IL-13 mRNA. gammaT treatment had no effect on IM increases by allergen, but blocked enhancement by ozone. gammaT attenuated both OVA- or ozone-stimulated eosinophilic infiltration, and increases of BALF cys-leukotrienes, MCP-1, and IL-6, as well as IL-5 and IL-13 mRNA. These data demonstrate broad anti-inflammatory effects of a gammaT and suggest that it may be an effective therapy of allergic airway inflammation. PMID- 17854714 TI - Activation of polymorphonuclear neutrophils in patients with impaired left ventricular function. AB - Activation of leukocytes and in particular polymorphonuclear neutrophils (PMN) has emerged as a critical confounder in the pathophysiology of cardiovascular disease: Myeloperoxidase (MPO), one of the principal proteins hosted in and secreted by activated PMN, has been mechanistically linked to endothelial and left ventricular (LV) dysfunction in rodent models of sepsis and ischemic cardiomyopathy. Whether PMN activation is also overt in patients with LV dysfunction of ischemic and nonischemic origin, however, remains elusive. Prospectively, 447 consecutive, stable outpatients were included in this single center study. In 113 patients with impaired left ventricular function (ejection fraction <50%; nonischemic cardiomyopathy, n=52; ischemic cardiomyopathy, n=61), MPO plasma levels were elevated (24.5 [IR:15.8-54.0] vs 15.5 [IR:8.9-39.2] ng/ml in controls, P<0.01) as was elastase (111.5 [IR:63.8-233.3] vs 70.5 [IR:45.0 129.0] ng/ml, P<0.01) and NT-proBNP plasma levels (747.4 [IR:216.3-1958.3] vs 264.1 [IR:82.5-671.8] ng/L, P<0.01). Elevation of circulating MPO was irrespective of the etiology of heart failure and independent of traditional confounding variables. No association was observed between MPO -463 promoter polymorphism genotype and LV dysfunction. MPO plasma levels correlated with ejection fraction (P<0.01) and left ventricular end-diastolic diameter (P<0.01), respectively. Myeloperoxidase mRNA expression levels obtained from circulating leukocytes were significantly increased in patients with LV dysfunction. Systemic leukocyte activation with increased transcription of MPO mRNA and augmented release of MPO appears to represent a so far underrecognized characteristic in LV dysfunction, which was revealed to be irrespective of the underlying pathology. Given its potent proinflammatory properties, MPO may represent an important mechanistic link to LV dysfunction and deserves to be evaluated as both marker and therapeutic target in this disease. PMID- 17854715 TI - Small interfering RNA-mediated silencing of mitochondrial NADP+-dependent isocitrate dehydrogenase enhances the sensitivity of HeLa cells toward tumor necrosis factor-alpha and anticancer drugs. AB - Tumor necrosis factor-alpha (TNF-alpha) and several anticancer drugs induce the production of reactive oxygen species, which play an important causative role in apoptotic cell death. Recently, we demonstrated that the control of mitochondrial redox balance and the cellular defense against oxidative damage is one of the primary functions of mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDPm) by supplying NADPH for antioxidant systems. In the present report, we show that silencing of IDPm expression in HeLa cells greatly enhances apoptosis induced by TNF-alpha and anticancer drugs. Transfection of HeLa cells with an IDPm small interfering RNA (siRNA) markedly decreased activity of IDPm, enhancing the susceptibility of anticancer agent-induced apoptosis reflected by morphological evidence of apoptosis, DNA fragmentation, cellular redox status, mitochondria redox status and function, and the modulation of apoptotic marker proteins. These results indicate that IDPm may play an important role in regulating the apoptosis induced by TNF-alpha and anticancer drugs and the sensitizing effect of IDPm siRNA on the apoptotic cell death of HeLa cells offers the possibility of developing a modifier of cancer chemotherapy. PMID- 17854716 TI - An electron paramagnetic resonance investigation of the oxygen dependence of the arterial-venous gradient of nitrosyl hemoglobin in blood circulation. AB - Whether there is a nitrosyl hemoglobin (HbNO) gradient between the venous and the arterial parts of the circulatory system is a very controversial issue in nitric oxide research. We have carefully evaluated the measurement of HbNO concentration in blood using EPR generated in vivo by the NO donor DEANO under various oxygen tensions. We found that the absolute concentrations of HbNO in venous and arterial blood were the same within experimental error, independent of hemoglobin saturation; only the ratios of 5-coordinate and 6-coordinate HbNO differed. The HbNO concentration increased when the oxygen concentration breathed by the rats decreased in a manner that was linear in hemoglobin saturation. These results do not support the existence of an arterial-venous gradient of HbNO under our experimental conditions. PMID- 17854717 TI - Aluminum: a potential pro-oxidant in sunscreens/sunblocks? PMID- 17854719 TI - Hepatitis C prevention and true harm reduction. PMID- 17854720 TI - How can hepatitis C be prevented in the long term? AB - Significant advances have been made in preventing HIV infection among injectors but we still know little about preventing hepatitis C (HCV). Both prevalence and incidence of hepatitis C can remain high among IDUs even in the context of widespread implementation of harm reduction programmes. We need to develop new ways to fill the knowledge gap regarding HCV prevention. One way is to learn from the experts--those IDUs who, after long-term injection in social milieus of high hepatitis C prevalence, nonetheless remain uninfected. We describe a recently commenced program of research that focuses on understanding the strategies, behaviours, and environmental factors associated with "staying safe". This represents a 180-degree turn in IDU research where the focus has traditionally been on risk. Since social, cultural and environmental factors, as well as the vagaries of human strategic discovery by drug users can vary among localities, researchers in four different contexts--New York City, Valencia, Sydney and London--are collaborating in parallel Staying Safe studies. These studies aim to provide the conceptual basis for developing a new generation of HCV prevention programs to assist both new and experienced IDUs to remain uninfected over the long run. PMID- 17854721 TI - HCV synthesis project: preliminary analyses of HCV prevalence in relation to age and duration of injection. AB - Early acquisition of hepatitis C virus (HCV) infection appears to affect a substantial proportion of injection drug users (IDUs)--between 20 percent and 90 percent. Analysing the range of HCV prevalence estimates in new injectors may help identify factors that can be modified to reduce HCV transmission. The HCV Synthesis Project is a meta-analysis of studies of HCV epidemiology and prevention in drug users worldwide. In this preliminary analysis, we examined data from 127 studies of IDUs that reported HCV prevalence in relation to age or year since onset of drug injection, analysing heterogeneity and calculating summary statistics where appropriate. Six studies reported gender-specific HCV prevalence rates among young or new injectors; the group mean prevalence was 47 percent for men and 44 percent for women (NS). Group mean age for HCV-negatives was 24.7 years (range 24-28) and 26.1 years (range 21-31) for HCV-positives (n=8 studies). Data were examined from 13 studies that compared HCV prevalence among young injectors to older injectors using 5-year age categories; substantial variation was present within these categories such that measures of central tendency were not calculated. Similarly, among studies reporting HCV prevalence among IDUs in relation to 1-year intervals of duration of injection (<1 year, <2 years, and <3 years), considerable variability was observed. Notably, there were studies in each category that reported prevalence of 70 percent or higher among recent-onset drug injectors. Our findings confirm previous studies reporting high risk of acquiring HCV shortly after onset of injection; thus, HCV prevention programmes must emphasize methods to reach new injectors. Future research should (1) report data on time to infection in depth, (2) provide detailed information on study methodology, and (3) characterize the research setting with respect to underlying factors that affect injection practices and networks. This will permit synthesis of a greater number of studies and may lead to the identification of factors that impede HCV transmission. PMID- 17854722 TI - Global estimates of prevalence of HCV infection among injecting drug users. AB - OBJECTIVE: In this paper, we review evidence of HCV prevalence among injecting drug users (IDUs) worldwide. METHODS: We undertook a desk-based review of both 'grey' and published literature released between 1998 and 2005. RESULTS: Data on HCV prevalence among IDUs was found in 57 countries and in 152 sub-national areas. We found reports of HCV prevalence of at least 50% among IDUs in 49 countries or territories. Available regional estimates varied widely, from 10 to 96% in Eastern Europe and Central Asia, from 10 to 100% in South and South-East Asia, from 34 to 93% in East-Asia and the Pacific, from 5 to 60% in North Africa and the Middle-East, from 2 to 100% in Latin America, from 8 to 90% in North America, from 25 to 88% in Australia and New Zealand, and from 2 to 93% in Western Europe. Only in Colombia and Lebanon were all HCV prevalence estimates below 20%. In addition, evidence of HIV/HCV co-infection among IDUs was found in 16 countries. In China, Poland, Puerto Rico, Russia, Spain, Switzerland, Thailand and Viet Nam, estimates of the prevalence of HIV/HCV co-infection among IDUs reached 90%. DISCUSSION: Taken together, data suggest high global prevalence of HCV and HIV/HCV co-infection among IDUs. We suggest exploring protective factors in sites of low HCV prevalence. PMID- 17854723 TI - Prevalence and correlates of hepatitis C virus infection among injecting drug users in Tehran. AB - This study aimed to investigate the prevalence and correlates of hepatitis C virus infection among injecting drug users in a community-based setting in Tehran, Iran. In October 2004, injecting drug users were recruited from a drop-in centre and neighboring parks and streets in a drug-populated neighborhood in Tehran. Participants were interviewed using a structured questionnaire, and a sample of oral mucosal transudate was collected for detection of HIV and HCV antibodies. Overall, 105 of 202 participants (52.0%) were found to be positive for HCV-antibody testing. After adjustment for the basic demographic characteristics, the prevalence of HCV infection was found to be associated with length of drug injection (more than 10 years) [odds ratio (OR), 3.25; 95% confidence interval (CI), 1.43-7.38], length of lifetime incarcerations (more than a year) (OR, 3.44; 95% CI, 1.68-7.06), and a history of being tattooed inside prison (OR, 1.96; 95% CI, 1.06-3.62). High prevalence of HCV infection and its association with incarceration-related exposures are important implications for harm reduction initiatives for drug using inmates in Iran. While prevention interventions for drug using inmates are being expanded in Iran, it is important that high prevalence of HCV infection be taken into consideration in order to control further transmission of this infection. PMID- 17854724 TI - The depiction of stigmatization in research about hepatitis C. AB - In the past decade, there has been an increasing emphasis by researchers regarding the stigmatization of people who are hepatitis C positive as they seek health care. Because the vast majority of people with hepatitis C have a history of injection drug use, they are frequently assumed by practitioners to be injection drug users (IDUs), blamed for acquiring the disease, and viewed as irresponsible, immoral, and unworthy. Such stigmatization may cause people who have hepatitis C to avoid testing, treatment and care, as well as to not disclose their hepatitis C or injection drug use to practitioners. The purpose of this paper is to critically examine the representation of stigmatization in 21 published research reports from 1995 to 2006, with a specific focus on how these depictions have shaped the current understanding of interventions to address stigmatization of people with hepatitis C by health care practitioners. We will identify two themes in this literature: (1) hepatitis C-related stigmatization in health care settings arises primarily from practitioners' negative views of injection drug use, and (2) practitioners' negative attitudes toward people with hepatitis C are the result of their lack of awareness and/or information about the disease and/or about injection drug use. We will illustrate that similar themes have informed anti-stigma initiatives in other diseases, notably HIV/AIDS and mental illness, which have had little sustained effect in changing practitioners' behaviour toward the stigmatized population. In conclusion, we will call for research that considers factors beyond the individual practitioner as contributing to the stigmatization of people with hepatitis C, such as social, structural and institutional forces that shape practitioners' interactions with people with hepatitis C in health care settings. PMID- 17854725 TI - The drugs that dare not speak their name: Injecting and other illicit drug use during treatment for hepatitis C infection. AB - Exploration of patients' illicit drug use during treatment for hepatitis C virus (HCV) infection is largely absent from the clinical literature. This paper explores injecting and other illicit drug use among people receiving interferon based treatment for HCV infection, from the perspective of one group of health professionals. Data are presented from a qualitative study of six health professionals responsible for managing HCV treatment regimens at three major metropolitan hospitals across Sydney, Australia. During semi-structured in-depth interviews, participants discussed patients' use of injected and non-injected illicit drugs while coping with a demanding therapeutic regimen. Health professionals highlighted the socially conservative environment of healthcare and its negative perceptions of illicit drug users. Also discussed are the management of people who inject during treatment and the efficacy of cannabis to reduce side effects. The findings of this study indicate that while the health professionals adopted a harm reduction approach to patients' illicit drug use during HCV treatment, information regarding the risks and benefits of illicit drug use is silenced in this context. While ever prohibition remains Australia's illicit drug policy this situation appears unlikely to change. Research which investigates the extent of illicit drug use during HCV treatment, the risks and benefits associated with their use in this context, and the harms of perpetuating a duplicitous healthcare system is required. PMID- 17854726 TI - Prejudice among health care workers toward injecting drug users with hepatitis C: does greater contact lead to less prejudice? AB - The current research measured explicit (self-reported) and implicit (or unconscious) attitudes of health care workers and their drug injecting clients with hepatitis C virus (HCV) toward each other, and the association of these attitudes with contact. Sixty health care workers and 120 of their clients with HCV acquired from injecting drug use were administered attitude measures to determine whether greater contact with HCV positive clients would result in more favourable attitudes on the part of health care workers toward these clients, and also on the part of these clients towards their health care workers. Findings suggest that increased contact with clients with HCV is associated with more favourable explicit attitudes and more negative implicit attitudes among health care workers toward injecting drug users. Health care workers who had greater contact with HCV positive clients also had HCV positive clients who held more favourable explicit attitudes toward health care workers, but contact was uncorrelated with implicit attitudes of clients toward health care workers. PMID- 17854727 TI - Everybody's got it, but...: situational and strategic participation in normalized HCV discourse among injection drug users in Edmonton, Canada. AB - BACKGROUND: The normalization thesis refers to processes whereby stigmatized individuals, groups, and activities are accommodated into everyday social life. This study explored the utility of normalization for understanding the social accommodation of HCV among street-involved injection drug users (IDUs) in a Canadian city. METHODS: In-depth semi-structured interviews (1-4 hr) were conducted with 61 drug injectors recruited through a harm reduction program and user networks in Edmonton's inner city. ANALYSES AND RESULTS: An inductive approach characterized common and unique themes across participants, using a combination of phenomenological and thematic analyses and the constant comparative method. Most respondents readily participated in a normalized discourse about HCV, wherein 'everybody's got it', transmission is unavoidable, and that being HCV+--while being less serious than HIV--is a defining characteristic of ID use. However, results indicated that participation in normalized HCV discourse was situational, strategic, and at times, contradictory with respect to (a) coping with HCV diagnosis and progression, (b) negotiating riskier or safer injection practices, and (c) disclosing serostatus to others. CONCLUSIONS: While normalization is useful for understanding the internalization of a medico-epidemiologic concept ('HCV status') into this user population, systematic description of coping and risk management practices relative to IDUs' acceptance or rejection of normalized expectations of HCV is important for developing tailored harm reduction programs and policies. PMID- 17854728 TI - Hepatitis C meanings and preventive strategies among street-involved young injection drug users in Montreal. AB - OBJECTIVE: To examine what hepatitis C virus (HCV) infection means to street involved young IDUs (SYIDUs) and how this impacts on their health behaviours, based on social contexts in which they live. METHODS: Thirty-nine SYIDUs with HCV infection participated in in-depth interviews. A typology was built founded on SYIDUs' street life and drug use experiences. The meanings given to hepatitis C and resulting health behaviours were examined through these experiences. RESULTS: In Montreal, "total" experience is characterised by an exclusive social relationship with the street milieu and by intensive drug consumption. In this milieu, where most injectors are HCV-infected but asymptomatic, getting infected is considered trivial. Compared to other more immediate threats, HCV infection and its long-term consequences are lesser concerns. Efforts to inject safely are made to avoid HIV. When these SYIDUs learn they are HCV-infected, they do not make important lifestyle changes. However, since they worry about transmitting the infection to others, they notify their injection partners that they are infected. SYIDUs living a "controlled" experience preserve some stability in their lives and control their consumption. They maintain relationships within mainstream society and have beliefs reflecting these links. They view HCV infection as a serious disease and make significant efforts to avoid sharing their injection equipment and thus remain healthy. When they learn they are HCV infected, they engage in "liver friendly" behaviours but are not ready to stop injecting. The "disengaging" experience is that of youth who start to disengage from drug injection. They leave the drug milieu and develop new relationships within mainstream society. They adopt new values regarding health. HCV infection is viewed as requiring significant changes in strategies aimed at protecting themselves and others. CONCLUSION: This research sheds light on the fundamentally social nature of hepatitis C. SYIDUs' HCV experiences, which evolve in parallel with their street life and consumption trajectories, provide numerous occasions where they can be exposed to prevention messages. PMID- 17854729 TI - Integrating HCV services for drug users: a model to improve engagement and outcomes. AB - Although the majority of prevalent and incident cases of hepatitis C are related to injection drug use, drug users often find it difficult to access treatment services because of concerns about adherence and treatment candidacy. In response to the growing epidemic, OASIS, a nonprofit community clinic, developed a successful peer-based HCV group that allowed us to engage, educate, test, and treat hepatitis C in large numbers of drug users, the majority of whom have multiple potential barriers to intervention. Integrating services for hepatitis C, addiction, mental health, and psychosocial problems, the model involves a collaboration of medical providers and peer educators and incorporates elements of other proven behavioural models, including self-help groups, therapeutic communities, and peer interventions. Our results indicate that this peer-based model is successful at engaging, educating, and treating a diverse spectrum of chaotic drug users. We conclude that an integrated, peer-based approach to intervention can engage even the most challenging addicted patients with hepatitis C, and can facilitate their successful screening and treatment. PMID- 17854730 TI - Education by peers is the key to success. AB - We are a Latino, a white guy and an African American, and we are all peer educators in the hepatitis C programme at Organization to Achieve Solutions in Substance Abuse, Inc. (OASIS), a not-for-profit medical clinic in Oakland, California. We are all recovering heroin users who got hepatitis C from using needles and we all managed to stop using drugs. In the same way, we all went through hepatitis C treatment; one of us was a sustained responder, one a non responder, and one a relapsing non-responder who is still on maintenance interferon. We have written this paper to tell our story. We believe that good education about hepatitis C encourages people to take better care of themselves, get tested and treated when necessary, and can motivate them to cut down or stop using drugs. In short, we use hepatitis C to encourage people to get their lives together. Many of the people we have educated go out to the community and educate other people who need it. We invite others to join our struggle, because we never thought we would make it this far. PMID- 17854731 TI - Integrating multiple programme and policy approaches to hepatitis C prevention and care for injection drug users: a comprehensive approach. AB - BACKGROUND: New York State is home to an estimated 230,000 individuals chronically infected with hepatitis C virus (HCV) and roughly 171,500 active injection drug users (IDUs). HCV/HIV co-infection is common and models of service delivery that effectively meet IDUs' needs are required. A HCV strategic plan has stressed integration. METHODS: HCV prevention and care are integrated within health and human service settings, including HIV/AIDS organisations and drug treatment programmes. Other measures that support comprehensive HCV services for IDUs include reimbursement, clinical guidelines, training and HCV prevention education. Community and provider collaborations inform programme and policy development. RESULTS: IDUs access 5 million syringes annually through harm reduction/syringe exchange programmes (SEPs) and a statewide syringe access programme. Declines in HCV prevalence amongst IDUs in New York City coincided with improved syringe availability. New models of care successfully link IDUs at SEPs and in drug treatment to health care. Over 7000 Medicaid recipients with HCV/HIV co-infection had health care encounters related to their HCV in a 12 month period and 10,547 claims for HCV-related medications were paid. The success rate of transitional case management referrals to drug treatment is over 90%. Training and clinical guidelines promote provider knowledge about HCV and contribute to quality HCV care for IDUs. Chart reviews of 2570 patients with HIV in 2004 documented HCV status 97.4% of the time, overall, in various settings. New HCV surveillance systems are operational. Despite this progress, significant challenges remain. DISCUSSION: A comprehensive, public health approach, using multiple strategies across systems and mobilizing multiple sectors, can enhance IDUs access to HCV prevention and care. A holisitic approach with integrated services, including for HCV-HIV co-infected IDUs is needed. Leadership, collaboration and resources are essential. PMID- 17854732 TI - HIV/hepatitis coinfection in eastern Europe and new pan-European approaches to hepatitis prevention and management. AB - ISSUES: HIV/hepatitis coinfection in Europe; WHO European clinical protocols on the management of people coinfected with HIV/AIDS and hepatitis B or C (HBV or HCV); stakeholder recommendations for better HCV services. INTRODUCTION: The increasing availability of highly active antiretroviral therapy throughout Europe and central Asia has changed comorbidity and mortality patterns among people living with HIV/AIDS (PLWHA) as liver disease has increasingly replaced AIDS as the cause of death in PLWHA in western European countries. The average prevalence of HCV among PLWHA is 40 per cent, and much higher in countries where the HIV epidemic is driven by injecting drug use. Access to hepatitis treatment for PLWHA and IDUs is still very limited in Europe due to a lack of clear clinical management guidelines for HIV/hepatitis coinfections, high costs and a national failure to recognise hepatitis as a critical health issue. DESCRIPTION: In October 2006, the WHO Regional Office for Europe issued protocols for the clinical management of HIV/HCV and HIV/HBV coinfections. They include diagnostic algorithms adjusted for resource availability, and guidelines for the management of patients who do not yet need treatment, those who need only hepatitis or only HIV/AIDS treatment, and those who need both. Though the protocols should provide practical guidelines for physicians and assist in the development of national treatment standards, there is still a need for targeted prevention, treatment and care interventions. To expand access to hepatitis prevention and treatment, public awareness needs to be raised and national political leaders need to address hepatitis as a public health issue. Effective public health measures include price reductions for anti-hepatitis drugs; targeted testing, counselling and prevention activities; increased access to hepatitis B and C treatment and to HBV vaccination for the populations most at risk. PMID- 17854733 TI - Improving access to HCV treatment: external jugular venepuncture can overcome problems with difficult venous access. AB - Many patients requiring antiviral treatment of chronic hepatitis C (HCV) have a background of significant injection drug use (IDU). In a proportion of patients, IDU results in difficulty with blood collection from conventional sites. We audited patients from the Liver Clinics and Drug Health Pharmacotherapy Service of The Royal Prince Alfred Hospital (RPAH) to determine the incidence of difficulty with blood collection. This survey identified the need for an innovative venous access strategy to better manage this group of patients. An external jugular venepuncture (EJV) protocol and education package was developed in collaboration with the Department of Anaesthetics, Gastroenterology and Liver Centre and HCV clinical nurse consultants (CNC). RPAH policy and procedure committee approved the protocol and patient information sheet. Patients with a history of difficulty with blood collection were eligible for the protocol. Patient satisfaction surveys were conducted. The initial survey of patients from the liver clinics and pharmacotherapy service identified that 48 percent had difficulty with blood collection from conventional sites. In the period October 2002 to July 2006, 29 patients (89 percent with history of IDU) were referred for EJV assessment. Major indications for EJV were for blood testing for initiation and monitoring of antiviral therapy and ongoing assessment of HCV infected patients. No adverse events resulted from the procedure. All patients surveyed report high levels of satisfaction with the technique compared to previous venous access attempts. EJV improves access to antiviral therapy and is a safe and effective technique for patients with difficult venous access (DVA). In addition, we have utilised EJV for post-transplant care of patients and used external jugular vein cannulation as vascular access for contrast imaging in hepatocellular carcinoma (HCC) assessment. PMID- 17854734 TI - Treatment uptake and outcomes among current and former injection drug users receiving directly observed therapy within a multidisciplinary group model for the treatment of hepatitis C virus infection. AB - Injection drug use accounts for the majority of incident and prevalent cases of hepatitis C virus (HCV) infection. However, very few injection drug users (IDUs) have received treatment for this condition given issues of medical or psychiatric co-morbidity, ongoing substance abuse and a widely held belief that such individuals will not be able to adhere to the requirements of therapy, including regular medical follow-up. With this in mind, we sought to evaluate HCV treatment uptake and outcomes among current and former IDUs attending a weekly peer support group and receiving directly observed HCV therapy. Utilizing the existing infrastructure for the management of addictive disease, we have developed a model of "one-stop shopping" whereby the treatment of addiction, HCV and other medical conditions are fully integrated, with the collaboration of nurses, counsellors, addiction specialists, infectious disease specialists, primary care physicians and researchers. Subjects interested in receiving treatment for HCV infection were referred to a weekly peer-support group and evaluated for treatment. Patients received therapy with pegylated interferon-alpha2a or -alpha2b, both in combination with ribavirin. All injections were directly observed. Overall, we observed a high uptake of HCV treatment among attendees, with 51 percent either receiving or about to receive therapy. To date, 18 patients have initiated treatment for HCV infection and 12 have completed therapy. Overall, 8/12 (67 percent) subjects achieved an end of treatment response (genotype 1, 67 percent; genotypes 2/3, 67 percent), despite ongoing drug use in 75 percent of patients during treatment. These data demonstrate that with the appropriate programs in place, a high uptake of HCV treatment can be achieved among IDUs referred to a peer-support group. Moreover, the treatment of HCV in current and former IDUs within a multidisciplinary DOT program can be successfully undertaken, resulting in ETRs similar to those reported in randomized controlled trials. PMID- 17854735 TI - The Jailbreak Health Project--incorporating a unique radio programme for prisoners. AB - Several studies in NSW have identified prisoners to be at high risk for blood borne viruses. The prevalence of hepatitis C among men in NSW correctional centres is 40% and over 60% among women. It is even higher among those with histories of injecting drug use. As part of the state's strategy to minimise the spread of blood borne viruses and promote healthy lifestyles among prisoners, the Community Restorative Centre broadcasts a weekly half hour radio programme to prisoners and the community. The project is funded through the NSW Health Department and aims to provide support to prisoners, ex-prisoners and their families. Jailbreak's success hinges on the participation of the very people [prisoners] the show wishes to target. The radio show is aimed specifically at broadcasting health promotion and harm-minimisation messages to prisoners and their supporters although this is not obvious. When you tune in to Jailbreak you will hear a diverse range of opinion, music and poetry from people caught up in the criminal justice system. Nevertheless at the heart of this exciting and challenging project is the delivery of engaging, relevant and clear health messages to prison inmates, ex-inmates and families in relation to HIV, hepatitis and sexual health. Since 2002, valuable health information, often in the form of personal stories, vignettes and quiz questions, can be heard in and around Sydney on 2SER 107.3 FM or online at http://www.2ser.com. Jailbreak has not been without controversy and has to balance the security focus of correctional authorities and the illegality of substance use in correctional centres with the need to convey messages to prisoners in relation to harm-minimisation. PMID- 17854736 TI - Recruitment and follow-up of injecting drug users in the setting of early hepatitis C treatment: insights from the ATAHC study. AB - Despite current injecting drug users (IDUs) being the major risk group for new hepatitis C virus (HCV) infections in most countries, they constitute a small minority of study populations in almost all studies of acute HCV infection treatment. The Australian Trial in Acute Hepatitis C (ATAHC) is examining natural history and treatment efficacy among predominantly IDU-acquired acute HCV. Recruitment is through an Australian network of primary and tertiary care sites. Eligible participants are offered treatment with pegylated-interferon alpha-2a (PEG-IFN) for 24 weeks, with both treated and untreated participants followed for up to three years. Quantitative and qualitative data on injecting behaviour is collected on study participants. Participants are regularly reviewed by a multidisciplinary team that includes the treating clinician, HCV clinic nurse, outreach worker and when necessary are referred to a drug and alcohol worker, social worker, psychiatrist or other appropriate services. A contact log records all interactions between participants and the study team. In September 2006, 121 subjects had been screened, 107 were enrolled and 75 had chosen to commence a 24 week course of PEG-IFN (HIV/HCV coinfected participants are treated with PEG IFN/ribavirin combination therapy). Eighty per cent of ATAHC participants reported IDU within the previous six months. Recruitment is planned to continue through mid-2007. Through a series of case reports, this paper describes factors that are potential barriers to recruitment, follow-up, and treatment of IDUs in the context of acute HCV infection. PEG-IFN adherence and toxicity, current substance use or mental health issues are not presenting as the only barriers to HCV treatment. Financial and transport difficulties, isolation and social support, and legal issues have been prominent and had the potential to impact on clinic attendance and treatment success. Our work suggests that by using a multidisciplinary approach, potential barriers to recruitment and follow-up of current IDUs to HCV treatment can be effectively addressed, and this highly marginalised population can be successfully engaged and treated. PMID- 17854737 TI - Long sleep duration: a risk to health or a marker of risk? PMID- 17854738 TI - Marital quality and the marital bed: examining the covariation between relationship quality and sleep. AB - The majority of adults sleep with a partner, and for a significant proportion of couples, sleep problems and relationship problems co-occur, yet there has been little systematic study of the association between close relationships and sleep. The association between sleep and relationships is likely to be bi-directional and reciprocal-the quality of close relationships influences sleep and sleep disturbances or sleep disorders influence close relationship quality. Therefore, the purpose of the present review is to summarize the extant research on (1) the impact of co-sleeping on bed partner's sleep, (2) the impact of sleep disturbance or sleep disorders on relationship functioning, and (3) the impact of close relationship quality on sleep. In addition, we provide a conceptual model of biopsychosocial pathways to account for the covariation between relationship functioning and sleep. Recognizing the dyadic nature of sleep and incorporating such knowledge into both clinical practice and research in sleep medicine may elucidate key mechanisms in the etiology and maintenance of both sleep disorders and relationship problems and may ultimately inform novel treatments. PMID- 17854740 TI - Leflunomide in psoriatic arthritis. AB - Psoriatic arthritis (PsA) is a common unique form of inflammatory arthritis associated with psoriasis. Its exact prevalence is unknown but 5-30% of the 2-3% of subjects of the general population affected with psoriasis are developing PsA. Typically PsA presents as an oligoarticular asymmetrical arthritis with predominant distal finger joint pattern, presence of spinal involvement enthesitis and dactylitis. There is evidence that T-cells play a key role in the immunopathology of PsA as well as Psoriasis. Leflunomide, a selective pyrimidine synthesis inhibitor with the property to inhibit T-cell activation and proliferation has been shown to improve both joint and skin symptoms in patients with PsA. Significant response rates have been observed for Psoriatic Arthritis Response Criteria (PsARC), modified ACR20 and PASI 50 after 24 weeks of treatment with 20 mg/d Leflunomide orally in a randomised, placebo controlled multicenter trial (TOPAS Study). Leflunomide treatment also improved quality of life and showed a favourable safety profile. It is therefore concluded that Leflunomide offers an efficacious, well tolerated, safe, and relatively inexpensive therapeutic option for the treatment of actively inflamed joints and psoriatic skin lesions in patients with PsA. PMID- 17854741 TI - Biologic therapies in psoriasis: a new therapeutic approach. AB - Chronic plaque psoriasis is an immune-mediated, inflammatory skin disease with a heavy burden on quality of life of patients. The disease has a chronic relapsing course and may be life long. Comorbid disorders include psoriatic arthritis, obesity, dyslipidemia, hypertension and an increased rate of cardiovascular disease. Conventional systemic treatments include methotrexate, cyclosporine and acitretin, which are associated with end organ toxicity that precludes long term therapy. Biological drugs are designed to selectively interfere with the immune mechanisms that induce psoriasis. Efalizumab is effective for skin psoriasis but not psoriatic arthritis. Anti-TNF-alpha agents (etanercept, infliximab and adalimumab) are active on both psoriasis and psoriatic arthritis. Infliximab is the most effective and rapid agent, but its safety profile may be less favourable. Moreover, efficacy can reduce over time. Etanercept is moderately active but has a better safety profile, and can be discontinued and re-used without loss of efficacy. The long term safety of all these agents has not been established. PMID- 17854742 TI - Vascular complications of scleroderma. AB - Systemic sclerosis (SSc) is a multiorgan disease characterized by injury to vascular wall and extensive damage of the microvessels. The injury of the vascular wall is characterized by the formation of megacapillaries and avascular areas. The reduced capillary density leads to clinical manifestations such as digital ulcers. These lesions are extremely painful and lead to substantial functional disability. Management of digital ulcers includes non-pharmacologic and pharmacologic modalities. Despite the reduced blood flow and reduced partial oxygen pressure levels, there is paradoxically no evidence for a sufficient angiogenesis in the skin of patients with SSc. Angiogenesis is strongly disturbed in SSc, as demonstrated by Nailfold Video-Capillaroscopy changes, the damage of the vessels evolves progressively from early to late stages and is characterized by different morphological aspects. Almost all patients develop Raynaud's phenomenon which, together with structural vasculopathy, results in ulceration and critical digital ischemia. Many of the severe internal organ complications of SSc are vascular, including pulmonary arterial hypertension (PAH) and scleroderma renal crisis. Structural vascular damage occurs in many vascular beds and contribute to pulmonary, renal, cardiac and gastrointestinal complications. SSc has a high case-specific mortality due to organ-based complications including PAH, lung fibrosis, renal failure and involvement of the gastrointestinal tract. PMID- 17854743 TI - Pathogenetic and clinical rationale for TNF-blocking therapy in psoriatic arthritis. AB - The classical definition of psoriatic arthritis (PsA) as an inflammatory arthritis associated with psoriasis reflects only in part the large spectrum of musculoskeletal disorders found in patients with psoriasis. In particular, enthesopathy, dactilytis, osteitis and axial involvement are frequently neglected and probably account for the unsatisfactory response of PsA to traditional drugs, such as NSAIDs, steroids and DMARDs. Furthermore, these drugs showed only a partial ability to influence radiographic progression and psoriasis. The new anti TNF agents, in particular etanercept but also infliximab and adalimumab, have demonstrated a comprehensive effectiveness on the multiple aspects of the PsA disease, including quality of life and slowing of radiographic progression. Despite this clear efficacy, the actual mechanisms by which TNF-blocking agents are able to obtain all these effects are still incompletely understood. However, the success of this therapy suggested one of the best ways for further research in the field of PsA. In this new fashion, the most stimulating hypotheses involving TNF are those regarding genetic predisposition, angiogenesis and osteoclastogenesis. PMID- 17854744 TI - Potential target of infliximab in autoimmune and inflammatory diseases. AB - Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine produced by many cell types (blood monocytes, macrophages, mast cells and endothelial cells), that play a key role in the pathogenesis of multiple autoimmune and nonautoimmune disorders. A number of large placebo-controlled trials have shown that infliximab, a chimeric monoclonal antibody against TNF-alpha, is effective and well tolerated in patients with Crohn's disease, rheumatoid arthritis and spondiloarthritides and has become a widely used treatment for these diseases. Preliminary data suggest that several forms of vasculitis appear responsive to TNF antagonists: Behcet's disease, Churg-Strauss vasculitis, polyarteritis nodosa, and giant cell arteritis, among others. Wegener's granulomatosis and sarcoidosis have been shown to improve with infliximab. Polymyositis/dermatomyositis may also be responsive to TNF blockade. TNF likely plays little role in Sjogren's syndrome as evidenced by the lack of efficacy of TNF antagonists. There is a rationale for using TNF blockade even in systemic lupus erythematosus, a prototype of autoantibody-mediated disease, and a pilot study seems to confirm this potential effective approach. A number of other more rare disorders also may be responsive to TNF blockade. We here review the current and prospective roles of infliximab in the treatment of autoimmune diseases and other conditions. PMID- 17854745 TI - Hyperprolactinemia and autoimmune diseases. AB - The autoimmune diseases are more common in females. The sex hormones have an important role in this gender bias, mainly estrogen and prolactin (PRL) which modulate the immune response. PRL is secreted from the pituitary gland and other organs and cells mainly the lymphocytes. PRL has an immunostimulatory effect and promotes autoimmunity: PRL impairs the negative selection of autoreactive B lymphocytes occurring during B cell maturation into fully functional B cells. PRL has an anti-apoptotic effect, enhances proliferative response to antigens and mitogens and enhances the production of immunoglobulins and autoantibodies. Hyperprolactinemia (HPRL) is observed in multi-organ and organ specific autoimmune diseases like systemic lupus erythematosus (SLE) rheumatoid arthritis (RA), Sjogren's syndrome (SS), Hashimoto's thyroiditis (HT) and multiple sclerosis (MS). There is no consistent correlation between PRL levels and disease activity. Murine models and small studies in SLE patients suggest some role of dopamine agonists in the therapy of those diseases. The genetic factor may have a role in humans as in animal models. The PRL isoform has an important effect on the bioactivity on prolactin receptors (PRL-Rs). PMID- 17854746 TI - Influenza vaccination of patients with systemic lupus erythematosus: safety and immunogenecity issues. AB - The influenza vaccine is highly efficacious in the general population; however there have been concerns about the safety, and immunogenecity of the vaccine in patients with SLE. Several studies have suggested that the immune response of patients with SLE to influenza vaccine is significantly lower than the general population, mainly in patients with age > or =50 years and those treated with prednisone. The vaccine is safe for patients with SLE and it does not affect the clinical manifestations of SLE including renal features, disease activity, or the requirement for steroids or cytotoxic drugs. However, the vaccine may trigger the generation of autoantibodies which is usually short term and is not associated with clinical significance. PMID- 17854747 TI - Beta2-glycoprotein I and its clinical significance: from gene sequence to protein levels. AB - In order to elucidate beta2-GPI at the DNA level and characterize its polymorphisms, mRNA expression, protein levels and clinical significance at each of these steps, a molecular review of beta2-GPI literature was performed. The human beta2-GPI complete nucleotide sequence has been reported and it consists of 8 exons separated by large introns. The beta2-GPI gene is polymorphic with four alleles. The distribution of point mutations can be significantly different between various racial populations. DNA variation studies of the beta2-GPI gene identified a total of 151 single-nucleotide polymorphisms, 26 of which are within regions with potential clinical significance. Southern blot analysis indicated the presence of one gene product only. An atypical TATA box and a hepatic nuclear factor-1 element are both essential for beta2-GPI promoter activity. Transcription factor binding sites for STAT, CREB, C/EBPbeta, NF-1, AP-1, NFAT, HNF-3beta and HNF-1 have been identified in the promoter region of the beta2-GPI gene by computer analysis. The beta2-GPI transcriptional signal of 1.5 kb was detected in Northern blot analysis and its 326-amino-acid sequence was found to be one of the most proline-rich eukaryotic proteins. Amino acid substitutions have been shown to be associated with loss of phospholipid binding, development and recognition of antiphospholipid antibodies. PMID- 17854748 TI - What is the role of rituximab in the treatment of rheumatoid arthritis? AB - Rituximab is a monoclonal antibody against CD20 that was developed for the treatment of relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Recent controlled trials have shown that B cell-targeted therapy with rituximab is effective in RA (which suggest that B lymphocytes may be critical in its pathogenesis of RA) and early exposure data suggest that the tolerability and safety profile of rituximab may be even better in RA than in NHL patients. Rituximab is generally well tolerated, with a low incidence of serious adverse events, including serious infections. Available evidence suggests that its clinical benefits depend on effective B cell depletion, and the fact that its novel mode of action leads to the depletion of B cells makes it distinct from other biological therapies for RA that target T cells and their related cytokines. Although complete peripheral B cell depletion is regularly seen in RA and other autoimmune diseases, especially systemic lupus erythematosus (SLE), incomplete depletion has been reported in a subset of patients, even after full dosing with rituximab. PMID- 17854749 TI - Associated autoantibodies in celiac disease. AB - Celiac disease (CD) is a life-long inflammatory autoimmune condition of the gastrointestinal tract affecting genetically susceptible individuals. Several autoimmune disorders are more prevalent in patients and their close relatives and that risk is gluten exposure duration related. The most frequent reported CD associated conditions are type 1 diabetes mellitus and autoimmune thyroiditis. Associated autoimmune antibodies are frequent in CD and their first-degree relatives, spanning anti-endocrine, anti-gastrointestinal, anti-nuclear, anti cytoskeleton and anti-neurological antibodies. More specifically, antibodies against thyroid and the endocrine pancreas, anti-gastric and liver, anti-nuclear constituents, anti-reticulin, actin, smooth muscle, calreticulin, desmin, collagens and bone, anti-brain, ganglioside, neuronal and blood vessel were described in sera of the patients in numerous studies. The common immunogenetic theories for the above associations are: sharing common HLA and non-HLA genes, antigenic mimicry, damage-induced neoantigen exposure, altered intestinal permeability, idiotype network dysregulation and epitope spreading. The CD associated autoantibodies enigma, being an epiphenomenon or pathogenic, remains unresolved and presents a challenging area for future research. PMID- 17854750 TI - Coronary involvement in Takayasu's arteritis. AB - Coronary involvement may appear in up to a third of patients with Takayasu's arteritis. This affliction may have a dominant impact on the clinical manifestations of the patient. Occlusion of the ostia of the left main coronary artery and of proximal segments of the coronary arteries is the most frequent finding of the coronary vasculature in patients with Takayasu's arteritis. Beyond the vasculitic process enhanced atherosclerosis has a significant and detrimental impact on the disease development. Revascularizations are often unsuccessful particularly when the inflammatory disease is not under satisfactory control. New techniques have been developed in order to use vessels that have not been damaged by the disease as grafts. PMID- 17854751 TI - Postpartum depression, an autoimmune disease? AB - Medical conditions with known etiology and typical peripartal/postpartal disease exacerbations are now, without exception, considered autoimmune in etiology. Postpartum psychiatric conditions, and especially postpartum depression, currently, however, are still not understood in their etiology. This paper suggests that the typical postpartum flare pattern, and other clinical characteristics, point towards an autoimmune etiology for (postpartum) depression. The high prevalence of (postpartum) depression led to its designation as a major public health problem. A better understanding of etiology and pathophysiology would greatly advance the, currently still inaccurate, diagnosis of the condition, and improve approaches towards prevention and treatment. PMID- 17854752 TI - AutoAbSC.Org -- Autoantibody Standardization Committee in 2006. AB - The Autoantibody Standardization Committee was established in the early 1980s based on the recognized needs for reference human autoimmune sera that were critical for academic, clinical, and industrial laboratories. To date, 14 reference reagents are available without charge from the Biological Reference Reagents distribution center at the Centers for Disease Control and Prevention. A web site has been developed under "AutoAbSC.Org" to communicate to the wider stakeholder community and to facilitate ongoing activities in continuing the mission in autoantibody standardization. PMID- 17854753 TI - The pathophysiology of HCV induced B-cell clonal disorders. AB - Hepatitis C virus (HCV) has been shown in epidemiologic studies to be associated with immune system disorders. Primarily disorders that stem from B-cell regulatory control disturbance, such as mixed cryoglobulinemia (MC) and non Hodgkin's lymphoma (NHL). The causative role of HCV in these disorders is supported by the response to anti-viral treatment. The understanding of the pathophysiological process leading from HCV infection to B-cell clonal expansion has improved significantly. Data supports an antigen-driven indirect stimulation of clonal expansion model, leading from oligoclonal to monoclonal expansion and in some instances to frank malignancy. HCV-E2 antigen has been suggested as a candidate antigen as well as NS3. Binding of the B-cell receptor by viral antigens coupled with direct binding of CD-81 by HCV-E2 has been shown to provide a strong proliferative signal. Additional regulatory elements are also affected in HCV-related B-cell clonal expansion, including the Fas and BLyS signaling mechanisms. Finally, genetic events such as bcl-2 rearrangement may also be involved in clonal expansion. In this review, evidence linking HCV with MC and NHL, as well as known events in the pathophysiological process are described. PMID- 17854754 TI - Fractal models for event-based and dynamical timers. AB - Some recent papers proposed to distinguish between event-based and emergent timing. Event-based timing is conceived as prescribed by events produced by a central clock, and seems to be used in discrete tasks (e.g., finger tapping). Emergent or dynamical timing refers to the exploitation of the dynamical properties of effectors, and is typically used in continuous tasks (e.g., circle drawing). The analysis of period series suggested that both timing control processes possess fractal properties, characterized by self-similarity and long range dependence. The aim of this article is to present two models that produce period series presenting the statistical properties previously evidenced in discrete and continuous rhythmic tasks. The first one is an adaptation of the classical activation/threshold models, including a plateau-like evolution of the threshold over time. The second one is a hybrid limit-cycle model, including a time-dependent linear stiffness parameter. Both models reproduced satisfactorily the spectral signatures of event-based and dynamical timing processes, respectively. The models also produced auto-correlation functions similar to those experimentally observed. Using ARFIMA modeling we show that these simulated series possess fractal properties. We suggest in conclusion some possible extensions of this modeling approach, to account for the effects of metronomic pacing, or to analyze bimanual coordination. PMID- 17854755 TI - Expression of toll-like receptors on antigen-presenting cells in patients with falciparum malaria. AB - The continuous release of blood-stage malaria parasites and their products can activate components of the innate immune system and induce the production of proinflammatory cytokines. Toll-like receptors (TLRs) have emerged as pattern recognition receptors, residing on/in innate immune cells whose function is recognizing specific conserved components on different microbes. The aim of this study was to determine the expression of TLR2, TLR4 and TLR9 on antigen presenting cells (APCs) in patients with mild and severe forms of falciparum malaria. Healthy individuals were used as controls. Peripheral blood mononuclear cells (PBMCs) were stained with specific monoclonal antibodies (mAbs) to investigate the percentage and the level of TLR expression by flow cytometry. Patients with severe and mild malaria showed increased surface expression of TLR2 and TLR4 on CD14(+)monocytes and myeloid dendritic cells (MDCs) and decreased intracellular expression of TLR9 on plasmacytoid dendritic cells (PDCs), compared to those of healthy controls. A significant decrease in the percentage of circulating CD14(+)monocytes and MDCs expressing TLR2 was found in both severe and mild malaria patients. These findings suggested that TLRs might play role in innate immune recognition in which the differential expression of TLRs on APCs could be regulated by the P. falciparum parasite. PMID- 17854756 TI - Anterior ischemic optic neuropathy in patients younger than 50 years. AB - PURPOSE: To characterize anterior ischemic optic neuropathy (AION) in patients younger than 50 years. DESIGN: Retrospective study. METHODS: Records of all AION patients seen between 1989 and 2006 were reviewed. Patients younger than 50 years when initial visual loss occurred were included. RESULTS: Of 727 consecutive patients with AION, 169 (23%) were younger than 50 years (median, 43 years; range, 13 to 49 years; 58% men; 93% White). Involvement was unilateral in 59% of patients and bilateral in 41%. At least one cardiovascular risk factor was found in 74% of patients. Hypercoagulable states and vasculitis were found in 8%. An underlying small or anomalous optic disk was found in 92% of eyes (210/230). Isolated disk anomalies (without systemic risk factors) were present in 26% of eyes. Final visual acuities were 20/40 or better in 64% of eyes and 20/200 or worse in 22%. Among patients with bilateral involvement, final visual acuity was similar in the two eyes in 70% of patients. Anemia and type I diabetes were associated significantly with fellow eye involvement. Recurrent AION in the same eye occurred in 6% of patients. CONCLUSIONS: AION in younger patients is not uncommon and represents 23% of AION patients in a tertiary neuro-ophthalmic service. Except for giant cell arteritis, ocular and systemic risk factors and associated disorders are similar to those described in older AION patients. Younger AION patients have better visual acuity outcomes but a higher risk of fellow eye involvement than older AION patients. PMID- 17854757 TI - Risk of visual impairment in children with congenital toxoplasmic retinochoroiditis. AB - PURPOSE: Reliable information is needed to counsel parents of children with congenital toxoplasmosis regarding the long-term risk of visual impairment resulting from ocular toxoplasmosis. DESIGN: Prospective cohort study of children with congenital toxoplasmosis identified by prenatal or neonatal screening. METHODS: After three years of age, ophthalmologists reported the site of retinochoroidal lesions and visual acuity and parents reported visual impairment. An ophthalmologist predicted the child's vision based on the last retinal diagram. Selection biases were minimized by prospective enrollment and data collection, high rates of follow-up, and exclusion of referred cases. RESULTS: Two hundred and eighty-one of 284 infected children who underwent ophthalmic examinations were followed up to a median age of 4.8 years. One in six children (49/281; 17%) had at least one retinochoroidal lesion, two-thirds of whom (32/49; 65%) had a lesion at the posterior pole. In children with retinochoroiditis who had visual acuity measured after 3 years of age, 94% (31/33) had normal vision in the best eye (6/12 Snellen or better), as did 91% of those with a posterior pole lesion (21/23). Analyses based on affected eyes showed that 42% (29/69) had a posterior pole lesion, of which just more than half (15/29, 52%) had normal vision, as did 84% (16/19) of eyes with a peripheral lesion alone. Vision predicted by the ophthalmologist was moderately sensitive (59%) but overestimated impairment associated with posterior pole lesions. Of 44 children with information on acuity, four (9%) had bilateral visual impairment worse than 6/12 Snellen. CONCLUSIONS: Severe bilateral impairment occurred in 9% of children with congenital toxoplasmic retinochoroiditis. Half the children with a posterior pole lesion and one in six of those with peripheral lesions alone were visually impaired in the affected eye. PMID- 17854758 TI - [Beta-blocker prescription and chronic obstructive pulmonary disease]. AB - The beta-blocker (BB) prescription remains insufficient despite guidelines, especially, for chronic heart failure. Patients suffering chronic obstructive pulmonary disease (COPD) are particularly less treated by BB. The level of evidence for BB prescription is however especially high and as we will focus on, the level of evidence for the safety of BB in the COPD context is convincing enough. We, thus, propose to review the existing literature in regard to this prescription of BB in the chronic heart failure, in the coronary artery disease and for high blood pressure in COPD patients. We then propose our approach to improve the level of prescription of BB in COPD patient really justifying this prescription in cardiology. PMID- 17854759 TI - Cell cycle-dependent caspase-like activity that cleaves p27(KIP1) is the beta(1) subunit of the 20S proteasome. AB - We previously described a caspase-like activity, which we termed KIPase that is implicated in the turnover of the mammalian cell cycle regulator p27(KIP1). KIPase cleaves a tetra-peptide substrate, Ac-DPSD-AMC, which mimics the target site in p27(KIP1), and inhibitors based on this tetra-peptide are ineffective against other known caspases. Here we describe the purification and characterization of KIPase, and trace its activity to the beta(1) subunit of the 20S proteasome. Further analyses revealed that the activity of the beta(1) subunit is up-regulated as cells enter the cell cycle without concomitant change in the levels of the proteasome beta(1), beta(2) or beta(5) subunits. To our knowledge, this is the first description of cell cycle regulation of the caspase like activity of the 20S proteasome. PMID- 17854760 TI - Human mitochondrial complex I assembly: a dynamic and versatile process. AB - One can but admire the intricate way in which biomolecular structures are formed and cooperate to allow proper cellular function. A prominent example of such intricacy is the assembly of the five inner membrane embedded enzymatic complexes of the mitochondrial oxidative phosphorylation (OXPHOS) system, which involves the stepwise combination of >80 subunits and prosthetic groups encoded by both the mitochondrial and nuclear genomes. This review will focus on the assembly of the most complicated OXPHOS structure: complex I (NADH:ubiquinone oxidoreductase, EC 1.6.5.3). Recent studies into complex I assembly in human cells have resulted in several models elucidating a thus far enigmatic process. In this review, special attention will be given to the overlap between the various assembly models proposed in different organisms. Complex I being a complicated structure, its assembly must be prone to some form of coordination. This is where chaperone proteins come into play, some of which may relate complex I assembly to processes such as apoptosis and even immunity. PMID- 17854761 TI - Structural and thermodynamic analyses of the interaction between melittin and lipopolysaccharide. AB - Lipopolysaccharide (LPS), the major constituent of the outer membrane of Gram negative bacteria, is the very first site of interactions with the antimicrobial peptides. In this work, we have determined a solution conformation of melittin, a well-known membrane active amphiphilic peptide from honey bee venom, by transferred nuclear Overhauser effect (Tr-NOE) spectroscopy in its bound state with lipopolysaccharide. The LPS bound conformation of melittin is characterized by a helical structure restricted only to the C-terminus region (residues A15 R24) of the molecule. Saturation transfer difference (STD) NMR studies reveal that several C-terminal residues of melittin including Trp19 are in close proximity with LPS. Isothermal titration calorimetry (ITC) data demonstrates that melittin binding to LPS or lipid A is an endothermic process. The interaction between melittin and lipid A is further characterized by an equilibrium association constant (Ka) of 2.85 x 10(6) M(-1) and a stoichiometry of 0.80, melittin/lipid A. The estimated free energy of binding (delta G0), -8.8 kcal mol( 1), obtained from ITC experiments correlates well with a partial helical structure of melittin in complex with LPS. Moreover, a synthetic peptide fragment, residues L13-Q26 or mel-C, derived from the C-terminus of melittin has been found to contain comparable outer membrane permeabilizing activity against Escherichia coli cells. Intrinsic tryptophan fluorescence experiments of melittin and mel-C demonstrate very similar emission maxima and quenching in presence of LPS micelles. The Red Edge Excitation Shift (REES) studies of tryptophan residue indicate that both peptides are located in very similar environment in complex with LPS. Collectively, these results suggest that a helical conformation of melittin, at its C-terminus, could be an important element in recognition of LPS in the outer membrane. PMID- 17854763 TI - Desmosome structure, composition and function. AB - Desmosomes are intercellular junctions of epithelia and cardiac muscle. They resist mechanical stress because they adopt a strongly adhesive state in which they are said to be hyper-adhesive and which distinguishes them from other intercellular junctions; desmosomes are specialised for strong adhesion and their failure can result in diseases of the skin and heart. They are also dynamic structures whose adhesiveness can switch between high and low affinity adhesive states during processes such as embryonic development and wound healing, the switching being signalled by protein kinase C. Desmosomes may also act as signalling centres, regulating the availability of signalling molecules and thereby participating in fundamental processes such as cell proliferation, differentiation and morphogenesis. Here we consider the structure, composition and function of desmosomes, and their role in embryonic development and disease. PMID- 17854762 TI - Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. AB - Adherens junctions and Tight junctions comprise two modes of cell-cell adhesion that provide different functions. Both junctional complexes are proposed to associate with the actin cytoskeleton, and formation and maturation of cell-cell contacts involves reorganization of the actin cytoskeleton. Adherens junctions initiate cell-cell contacts, and mediate the maturation and maintenance of the contact. Adherens junctions consist of the transmembrane protein E-cadherin, and intracellular components, p120-catenin, beta-catenin and alpha-catenin. Tight junctions regulate the paracellular pathway for the movement of ions and solutes in-between cells. Tight junctions consist of the transmembrane proteins occludin and claudin, and the cytoplasmic scaffolding proteins ZO-1, -2, and -3. This review discusses the binding interactions of the most studied proteins that occur within each of these two junctional complexes and possible modes of regulation of these interactions, and the different mechanisms that connect and regulate interactions with the actin cytoskeleton. PMID- 17854764 TI - Investigating the effects of tic suppression on premonitory urge ratings in children and adolescents with Tourette's syndrome. AB - Tics represent a complex class of behaviors that have a neurobiological origin and are influenced by factors both internal and external to the individual. One factor that has gained recent attention is the premonitory urge. Contemporary behavioral models suggest that some tics are preceded by aversive somatic urges that increase in severity when tics are suppressed and are attenuated by performance of the tic. It has been proposed that the removal of premonitory urges may strengthen or maintain tics via negative reinforcement. This investigation is the first to empirically evaluate the effect of tic suppression on the premonitory urge phenomenon. Five children and adolescents, ages 8 17years, participated in the study. Using an ABAB reversal design, tic frequency and subjective premonitory urge ratings were recorded under conditions of free-to tic baseline (BL) and reinforced tic suppression (differential reinforcement of zero-rate behavior). Results show that four of the five children demonstrated reliable suppression. Of the four children who achieved suppression, three demonstrated a pattern in which subjective urge ratings were higher during suppression than during BL. Results provide preliminary support for the negative reinforcement view of tic function for some children. PMID- 17854765 TI - The psychological processes underlying symptoms of thought interference in psychosis. AB - Morrison and colleagues have proposed that auditory hallucinations are the result of cognitive intrusions being misattributed to an external source due to such thoughts being inconsistent with the person's beliefs about his or her own mental processes (metacognitive beliefs). The aim of this study was to investigate the applicability of this model to psychotic symptoms of thought interference. Fifty psychotic patients with and without thought interference were compared on (i) frequency of cognitive intrusions, (ii) metacognitive beliefs, (iii) source monitoring and (iv) appraisals of an unrelated anomalous event (a card trick). As predicted, individuals with thought interference had an increased frequency of cognitive intrusions and of maladaptive metacognitive appraisals, lower perceived cognitive control, and were more likely to endorse appraisals regarding 'permeability' of the mind, on the card trick task, in comparison to individuals without thought interference. No significant differences were found on any measure when the patient group was divided into hallucinators and non hallucinators, once other variables were controlled for. These findings suggest that Morrison's model may be more parsimonious for symptoms of thought interference than for auditory hallucinations. PMID- 17854767 TI - Interactions of cell penetrating peptide Tat with model membranes: a biophysical study. AB - The protein transduction domain of the HIV-1 transactivator of transcription, Tat (Tat((48-60))), has been shown to transport P10, a cytotoxic peptide mimic of the cyclin dependent kinase inhibitor p21WAF1/CIP1, into the nucleus of cancerous cells and induce apoptosis. Here, monolayer studies were used to investigate the membrane interactions of Tat((48-60)), P10 and the construct Tat((48-60))P10. It was found that Tat((48-60)) showed no significant surface activity but that both P10 and Tat((48-60))P10, were highly surface active, inducing surface pressure changes of 9.7 and 8.9mNm(-1), respectively, with DMPS monolayers. The comparison of Tat((48-60))P10 and P10 surface interactions would be consistent with a hypothesis that the cargo attachment influences the capacity of the Tat-protein transduction domain to mediate transport across membranes either directly or via localisation of the construct at the membrane interface. PMID- 17854766 TI - Increased perceived stress is associated with blunted hedonic capacity: potential implications for depression research. AB - Preclinical studies suggest that stress exerts depressogenic effects by impairing hedonic capacity; in humans, however, the precise mechanisms linking stress and depression are largely unknown. As an initial step towards better understanding the association between stress and anhedonia, the present study tested, in two independent samples, whether individuals reporting elevated stress exhibit decreased hedonic capacity. The Perceived Stress Scale (PSS) measured the degree to which participants appraised their daily life as unpredictable, uncontrollable, and overwhelming. Hedonic capacity was objectively assessed using a signal-detection task based on a differential reinforcement schedule. Decreased reward responsiveness (i.e., the participants' propensity to modulate behavior as a function of reward) was used as an operational measure of hedonic capacity. In both Study 1 (n=88) and Study 2 (n=80), participants with high PSS scores displayed blunted reward responsiveness and reported elevated anhedonic symptoms. Additionally, PSS scores predicted reduced reward responsiveness even after controlling for general distress and anxiety symptoms. These findings are consistent with preclinical data highlighting links between stress and anhedonia, and offer promising insights into potential mechanisms linking stress to depression. PMID- 17854768 TI - Emulating a crowded intracellular environment in vitro dramatically improves RT PCR performance. AB - The polymerase chain reaction's (PCR) phenomenal success in advancing fields as diverse as Medicine, Agriculture, Conservation, or Paleontology is based on the ability of using isolated prokaryotic thermostable DNA polymerases in vitro to copy DNA irrespective of origin. This process occurs intracellularly and has evolved to function efficiently under crowded conditions, namely in an environment packed with macromolecules. However, current in vitro practice ignores this important biophysical parameter of life. In order to more closely emulate conditions of intracellular biochemistry in vitro we added inert macromolecules into reverse transcription (RT) and PCR. We show dramatic improvements in all parameters of RT-PCR including 8- to 10-fold greater sensitivity, enhanced polymerase processivity, higher specific amplicon yield, greater primer annealing and specificity, and enhanced DNA polymerase thermal stability. The faster and more efficient reaction kinetics was a consequence of the cumulative molecular and thermodynamic effects of the excluded volume effect created by macromolecular crowding. PMID- 17854769 TI - FIP2 and Rip11 specify Rab11a-mediated cellular distribution of GLUT4 and FAT/CD36 in H9c2-hIR cells. AB - Rab11a has been shown to be involved in different vesicle trafficking processes. To further define the functional role of Rab11a in vesicle movement we knocked down gene expression of Rab11a and two of its effectors, Rip11 and FIP2, in H9c2 hIR cells and measured the cell surface abundance of GLUT4myc and FAT/CD36. We observed that by knocking down Rab11a, both GLUT4myc and FAT/CD36 abundance at the plasma membrane were substantially increased. In the case of GLUT4myc, the in vitro knockdown of FIP2 also increased the cell surface abundance of GLUT4myc. Knockdown of both FIP2 and Rip11 increase the abundance of FAT/CD36 at the plasma membrane. Stimulated translocation of GLUT4myc and FAT/CD36 is not altered after gene knockdown of Rab11a. These data therefore show that (i) Rab11a regulates cell surface abundance of both GLUT4 and FAT/CD36 and that (ii) both Rab11a dependent processes are differently regulated by Rab11a effector proteins. PMID- 17854770 TI - Potent inhibition of tau fibrillization with a multivalent ligand. AB - Small-molecule inhibitors of tau fibrillization are under investigation as tools for interrogating the tau aggregation pathway and as potential therapeutic agents for Alzheimer's disease. Established inhibitors include thiacarbocyanine dyes, which can inhibit recombinant tau fibrillization in the presence of anionic surfactant aggregation inducers. In an effort to increase inhibitory potency, a cyclic bis-thiacarbocyanine molecule containing two thiacarbocyanine moieties was synthesized and characterized with respect to tau fibrillization inhibitory activity by electron microscopy and ligand aggregation state by absorbance spectroscopy. Results showed that the inhibitory activity of the bis thiacarbocyanine was qualitatively similar to a monomeric cyanine dye, but was more potent with 50% inhibition achieved at approximately 80nM concentration. At all concentrations tested in aqueous solution, the bis-thiacarbocyanine collapsed to form a closed clamshell structure. However, the presence of tau protein selectively stabilized the open conformation. These results suggest that the inhibitory activity of bis-thiacarbocyanine results from multivalency, and reveal a route to more potent tau aggregation inhibitors. PMID- 17854771 TI - A mev-1-like dominant-negative SdhC increases oxidative stress and reduces lifespan in Drosophila. AB - Oxidative stress is thought to promote aging by damaging various cellular components. We investigated the phenotypic effects of mutation in the sdhC gene encoding succinate dehydrogenase C in Drosophila by using transgenic flies expressing a dominant-negative form, SdhC(I71E). Expression of SdhC(I71E) significantly reduced the mean lifespan by 22% compared to that of control flies. The amount of protein carbonyl was significantly increased, suggesting that a high level of oxidative stress was induced in these flies. The transgenic flies should serve as a model for studying the biological processes associated with increased levels of oxidative stress and mitochondrial dysfunction in Drosophila. PMID- 17854772 TI - Clearance of oxidized erythrocytes by macrophages: involvement of caspases in the generation of clearance signal at band 3 glycoprotein. AB - Human erythrocytes exposed to appropriate concentrations of H(2)O(2) for 1h became susceptible to the binding and phagocytosis by macrophages. The binding was inhibited by anti-band 3 serum and prevented by pretreatment of erythrocytes with a polylactosamine-cleaving enzyme endo-beta-galactosidase, indicating that polylactosaminyl sugar chains of band 3 are recognized by macrophages. The macrophage receptor involved was suggested to be nucleolin, a recently identified macrophage surface protein recognizing sialylpolylactosaminyl-chain clusters on early apoptotic cells, because anti-nucleolin antibody and a soluble form of recombinant nucleolin blocked the recognition. Treatment of erythrocytes with caspase inhibitors Z-VAD-fmk or Z-DQMD-fmk (caspase 3 selective) before the oxidation resulted in lowered binding of the oxidized erythrocytes to macrophages, suggesting that actions of caspases, particularly those of caspase 3, are prerequisite for the membrane changes leading to band 3 aggregation. Moreover, the cytosolic caspase 3 was found to be activated by H(2)O(2), and the extent of the activation correlated well with the susceptibility of the oxidized erythrocytes to the macrophage recognition. These results suggest that oxidative stress renders the erythrocytes susceptible to clearance by macrophages through activation of caspases leading to band 3 aggregation. PMID- 17854773 TI - Orotate phosphoribosyltransferase expression level in tumors is a potential determinant of the efficacy of 5-fluorouracil. AB - Although the intratumoral expression levels of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are known to affect the antitumor activity of 5-fluorouracil (5-FU), the importance of orotate phosphoribosyltransferase (OPRT) has remained unclear. This study investigated the relationship between intratumoral OPRT expression and the antitumor activity of 5-FU using human NCI60 cell lines with similar levels of TS and DPD messenger RNAs, as well as 31 tumor xenografts. The OPRT mRNA level was positively correlated with the 5-FU efficacy in these cell lines. In vitro, the 50% growth-inhibitory concentrations of 5-FU were closely correlated with the OPRT mRNA levels in cancer cell lines with similar levels of TS mRNAs when combined with a DPD inhibitor. Moreover, downregulation of OPRT with small-interfering RNA decreased the sensitivities of the cultured tumor cells to 5-FU. These results suggest that the OPRT expression level in tumors is an additional determinant of the efficacy of 5-FU. PMID- 17854775 TI - A-366833: a novel nicotinonitrile-substituted 3,6-diazabicyclo[3.2.0]-heptane alpha4beta2 nicotinic acetylcholine receptor selective agonist: Synthesis, analgesic efficacy and tolerability profile in animal models. AB - 5-[(1R,5S)-3,6-Diazabicyclo[3.2.0]heptan-6-yl]nicotinonitrile (A-366833) is a novel nicotinic acetylcholine receptor (nAChR) ligand that binds to the agonist binding site ([3H]-cytisine) with Ki value of 3.1 nM and exhibits agonist selectivity at alpha4beta2 nAChR relative to the alpha3beta4 nAChR subtype. The analgesic effects of A-366833 were examined across a variety of animal models including the mouse model of writhing pain (abdominal constriction), the rat models of acute thermal (hot box), persistent chemical (formalin) and neuropathic (spinal nerve ligation, SNL) pain. In the abdominal constriction model, A-366833 was effective at doses ranging from 0.062 to 0.62 micromol/kg (i.p.). In addition, A-366833 demonstrated significant effects in acute thermal pain (6.2 19.0 micromol/kg, i.p.), formalin (1.9-19 micromol/kg i.p.) and SNL (1.9-19 micromol/kg i.p.) models. The systemic effects of A-366833 were attenuated by pretreatment with mecamylamine (5 micromol/kg i.p.) in both the formalin and SNL models, suggesting that the analgesic effects of A-366833 in models of persistent nociceptive and neuropathic pain are mediated by activation of nAChRs. Pharmacokinetic investigations of A-366833 in rat revealed moderate brain:plasma distribution, half-life of 1.5h and excellent oral bioavailability of 73%. Comparison of peak plasma levels at the minimal effective doses across rat models of acute thermal pain, formalin and SNL with the maximal exposure that does not evoke emesis in ferret revealed therapeutic margins ranging from 6- to 22-fold. These studies indicate that compounds like A-366833 with improved agonist selectivity at alpha4beta2 vs. alpha3beta4 nAChR can elicit a broad spectrum of analgesic efficacy without concurrent adverse effects. PMID- 17854774 TI - CART peptides as modulators of dopamine and psychostimulants and interactions with the mesolimbic dopaminergic system. AB - Cocaine- and amphetamine-regulated transcript (CART) peptides (CART 55-102 and CART 62-102) are peptidergic neurotransmitters that are widely but specifically distributed throughout the brain, gut and other parts of the body. They are found in many brain regions associated with drug addiction including the nucleus accumbens, ventral tegmental area and ventral pallidum. Injections of CART 55-102 into the nucleus accumbens have no effect on basal locomotor activity. However, an injection of CART just before an i.p. injection of cocaine reduces the locomotor activating effects of cocaine. These and other data suggest that CART in the accumbens blunts the effects of cocaine. A hypothesis is that CART is homeostatic in the accumbens and tends to oppose large increases in dopamine signaling. These actions would therefore be able to regulate the effects of some abused drugs such as the psychostimulants. PMID- 17854776 TI - The neurochemical nature of PrP(c)-containing cells in the rat brain. AB - The cellular prion protein (PrP(C)) is a membrane-bound glycoprotein abundantly expressed in neurons and glial cells within the CNS. The scrapie prion protein (PrP(Sc)) is a conformationally altered isoform of PrP(C) that is responsible for prion diseases, also termed transmissible spongiform encephalopathies (TSE), a group of neurodegenerative diseases that affect a wide variety of mammal species, including humans. The presence of the cellular isoform of PrP is necessary for the establishment and further evolution of prion diseases and the physiological conditions where PrP(C) is present seems to modulate the alterations in TSE. In this work, the presence of PrP(C) in GABAergic, glutamatergic, nitrergic, cholinergic, serotoninergic and orexinergic populations of cells within the rat brain is examined. Our observations show that PrP(C) is widely expressed in a subset of neurons that contain markers of inhibitory populations of cells throughout the rat brain. The presence of PrP(C) in other cells types containing important neurotransmitters for the overall brain function is congruent with the imbalances reported for some of them in TSE. Within the cerebral cortex, PrP(C) is scarcely located in a subset of cells expressing the laminin receptor precursor (LRP) to such a low extent that suggests that other LRP-independent mechanisms actively participate during the pathogenic process. Taken together, our data demonstrate that investigation of the chemical partners of PrP(C) within cells gives a rational basis for the interpretation of the histopathological alterations in TSE and might help analyze some pathogenic mechanisms of PrP(Sc). PMID- 17854777 TI - Influence of environmental enrichment on steady-state mRNA levels for EAAC1, AMPA1 and NMDA2A receptor subunits in rat hippocampus. AB - Interaction with the environment has a key role in refining the neuronal circuitry required for normal brain function throughout life. Profound effects of enriched environment have been shown on neuronal structure and chemistry in experimental animals. Epidemiological studies imply that this is true also in man, thus cognitive stimulation has a protective effect on neurodegeneration, e.g., in Alzheimer's disease. Glutamatergic pathways are imperative for cognitive functions, such as memory, learning and long-term potentiation, and relies on the AMPA and NMDA glutamate receptors and the hippocampus, with its specific subregions, is an important anatomical substrate in this. The glutamate signalling is also dependent on a fine-tuned transport system, in the hippocampus primarily achieved by the glutamate transporter EAAC1. In this study we show how environmental enrichment modulates these parts of the glutamatergic system using quantitative in situ hybridisation. This work demonstrates for the first time that environmental enrichment modulates the mRNA expression of EAAC1 which is significantly and region specifically decreased in the hippocampus. We also provide evidence for regional and hemisphere-specific upregulation of NMDA mRNA in the hippocampus after environmental enrichment. The current work also shows that AMPA mRNA of the hippocampus is not per se changed by environmental enrichment in adult animals. Taken together, our results extend the knowledge of the glutamatergic system of specific regions of the hippocampus and its modulation by environmental enrichment and could contribute to the development of strategies aimed at limiting pathological changes associated with glutamatergic dysfunctions. PMID- 17854778 TI - BDNF up-regulates pre-pro-TRH mRNA expression in the fetal/neonatal paraventricular nucleus of the hypothalamus. Properties of the transduction pathway. AB - Brain derived neurotrophic factor (BDNF) increases the levels of pre-pro thyrotropin releasing hormone (TRH) mRNA in fetal rodent hypothalamic neurons that express TrkB receptors. The present studies aimed at better understanding the role of BDNF in establishing and maintaining the TRH phenotype in hypothalamic neurons during early development. To determine where BDNF regulates the expression of pre-pro-TRH mRNA in vivo, we compared the hypothalamic distribution of pre-pro-TRH mRNA to that of TrkB mRNA. Full-length TrkB (FL-TrkB) mRNA was detected earlier in development than pre-pro-TRH mRNA in the region that gives rise to the paraventricular nucleus of the hypothalamus (PVN). We also evaluated the effects of BDNF on the expression of pre-pro-TRH mRNA in vitro. BDNF up-regulated the levels of pre-pro-TRH mRNA in primary cell cultures obtained from the hypothalamus or the PVN of 17 days old fetuses or newborn rats. This effect was abolished by PD98059, an inhibitor of the mitogen-activated protein kinase kinase (MEK) 1/2 or 5. The effect of BDNF on pre-pro-TRH mRNA levels was reversible. The continuous application of BDNF led to a desensitization of the response at day 10 in vitro, an effect that correlated with a drop in the levels of FL-TrkB protein. In conclusion, BDNF enhances the expression of pre-pro-TRH mRNA in PVN neurons. This effect is reversible, decreases with time, and requires an active MEK. BDNF may contribute to the enhancement of pre-pro-TRH mRNA expression in the hypothalamic PVN during development. PMID- 17854779 TI - Ontogeny of steroid receptor coactivators in the hippocampus and their role in regulating postnatal HPA axis function. AB - The function and regulation of the hypothalamic-pituitary-adrenal (HPA) axis during ontogeny differs markedly from the situation in adult animals. Postnatally mice undergo a so-called stress hypo-responsive period, which is characterized by a relative inability of mild stressors to induce a marked corticosterone response. Steroid receptor coactivators (SRCs) have been shown to influence the function of the HPA axis in adult animals by interacting with steroid receptors as the mineralocorticoid and the glucocorticoid receptor. Here we test the hypothesis that expression changes of the three identified SRC genes (SRC1, SRC2 and SRC3) correlate with differences in HPA axis activity during postnatal development. First, we mapped the ontogeny of the three SRCs during postnatal development in the hippocampus. We found a time- and region-specific regulation of gene expression, which was specific for each SRC. However, there was no relation between the age-dependent stress system activity and the expression levels of the SRCs. Further, we studied the acute regulation of the three SRCs following maternal deprivation in 9-day-old wild-type or CRH receptor type 1 (CRHr1) knockout mice. Under these conditions, no differential expression of any of the tested SRCs could be detected. Thus, while it seems likely that their varying abundance throughout postnatal life affects steroid receptor function in the different hippocampal subregions, acute changes of HPA axis activity or reactivity are not mediated by hippocampal changes in expression of this coactivator family. PMID- 17854780 TI - Sensory experience determines enrichment-induced plasticity in rat auditory cortex. AB - Our previous studies demonstrated that only a few days of housing in an enriched environment increases response strength and paired-pulse depression in the auditory cortex of awake and anesthetized rats [Engineer, N.D., Percaccio, C.R., Pandya, P.K., Moucha, R., Rathbun, D.L., Kilgard, M.P., 2004. Environmental enrichment improves response strength, threshold, selectivity, and latency of auditory cortex neurons. J Neurophysiol. 92, 73-82 and Percaccio, C.R., Engineer, N.D., Pruette, A.L., Pandya, P.K., Moucha, R., Rathbun, D.L., Kilgard, M.P., 2005. Environmental enrichment increases paired-pulse depression in rat auditory cortex. J Neurophysiol. 94, 3590-3600]. Multiple environmental and neurochemical factors likely contribute to the expression of this plasticity. In the current study, we examined the contribution of social stimulation, exercise, auditory exposure, and cholinergic modulation to enrichment-induced plasticity. We recorded epidural evoked potentials from awake rats in response to tone pairs and noise bursts. Auditory evoked responses were not altered by social stimulation or exercise. Rats that could hear the enriched environment, but not interact with it, exhibited enhanced responses to tones and increased paired-pulse depression. The degree to which enrichment increased response strength and forward masking was not reduced after a ventricular injection of 192 IgG-saporin. These results indicate that rich auditory experience stimulates physiological plasticity in the auditory cortex, despite persistent deficits in cholinergic activity. This conclusion may be beneficial to clinical populations with sensory gating and cholinergic abnormalities, including individuals with autism, schizophrenia, and Alzheimer's disease. PMID- 17854782 TI - Structural analysis of a water-soluble glucan (Fr.I) of an edible mushroom, Pleurotus sajor-caju. AB - A water-soluble glucan was obtained from the fruit bodies of an edible mushroom, Pleurotus sajor-caju, by hot water extraction, ethanol precipitation, dialysis, and Sepharose 6B gel filtration. On the basis of total hydrolysis, methylation analysis, periodate oxidation, and NMR studies ((1)H, (13)C, DQF-COSY, TOCSY, NOESY, and HSQC), the structure of the repeating unit of the glucan is determined as [carbohydrate structure: see text]. PMID- 17854781 TI - Effect of chronic administration of ethanol on the regulation of the delta subunit of GABA(A) receptors in the rat brain. AB - In the present study, we investigated the effect of chronic ethanol (CE) administration on the polypeptide levels of the delta-subunit of GABA(A) receptors and [(3)H]muscimol binding to the immunoprecipitated delta-subunit containing GABA(A) receptor assemblies in the rat brain. CE administration resulted a down-regulation of polypeptide levels of the delta-subunit of GABA(A) receptors in the rat cerebellum and hippocampus, whereas there were no changes in the delta-subunit polypeptide levels in the rat cerebral cortex. Further, CE administration caused a down-regulation of native delta-subunit-containing GABA(A) receptor assemblies in the rat cerebellum as determined by [(3)H]muscimol binding to the immunoprecipitated receptor assemblies. These results indicate that the delta-subunit-containing GABA(A) receptors may play a role in chronic ethanol-induced tolerance and dependence. PMID- 17854783 TI - A comparative study of different glycosylation methods for the synthesis of D mannopyranosides of Nalpha-fluorenylmethoxycarbonyl-trans-4-hydroxy-L-proline allyl ester. AB - The synthesis of Nalpha-fluorenylmethoxycarbonyl-trans-4-hydroxy-4-O-[(2,3,4,6 tetra-O-acetyl)-alpha-d-mannopyranosyl]-l-proline allyl ester and Nalpha fluorenylmethoxycarbonyl-trans-4-hydroxy-4-O-[(2,3,4,6-tetra-O-benzoyl)-alpha-d mannopyranosyl]-l-proline allyl ester is described. Glycosylation using Konigs Knorr conditions with a benzoyl protected glycosyl donor provided the optimum method. Removal of the allyl ester gave two mannosylated building blocks suitable for solid phase glycopeptide synthesis. PMID- 17854784 TI - First example of 5/6-O-linked pseudosaccharides: synthesis of bicyclic nucleosides containing azido or extended carbohydrate moiety. AB - Treatment of the d-glucose-derived substrate 1 with sodium hydride in tetrahydrofuran provided 3,6-anhydro monosaccharide 2, along with the 5,6-ether linked pseudodisaccharide 3, and pseudotrisaccharide 4. However, reaction of 1 with sodium ethoxide in ethanol afforded 2 as the sole product, elaborated to the bicyclic azidonucleosides 9 and 16. Acetylated bicyclic nucleosides 17-19 with extended carbohydrate residues have been synthesized from 3. PMID- 17854785 TI - Structural analysis of linear hydroxyproline-bound O-glycans of Chlamydomonas reinhardtii--conservation of the inner core in Chlamydomonas and land plants. AB - Linear hydroxyproline-bound O-glycans of the unicellular green alga Chlamydomonas reinhardtii were isolated from outer cell wall glycoproteins and their structure elucidated by chemical and spectroscopic methods. They consist exclusively of arabinose and galactose, the latter in the furanose form, unusual for plants. The first two arabinoses linked to hydroxyproline have the same anomeric configuration and linkage to each other as do the arabinosides isolated from land plants, suggesting that these two steps of hydroxyproline-O-glycosylation have been conserved during evolution. In a concomitant analysis of Hyp-bound O-tri- and tetraarabinans isolated from Arabidopsis thaliana, we were able to unambiguously identify the natural trans-4-l-Hyp-bound O-glycans and the artificially produced d-allo forms and to identify diagnostic signals in NMR spectra of these compounds for the first time. PMID- 17854786 TI - Characterization of a novel SCN5A mutation associated with Brugada syndrome reveals involvement of DIIIS4-S5 linker in slow inactivation. AB - OBJECTIVE: Mutations in SCN5A, the gene encoding the alpha-subunit of the cardiac sodium channel (Na(v)1.5), have been associated with various inherited arrhythmia syndromes, including Brugada syndrome (BrS). Here, we report the functional consequences of a novel missense SCN5A mutation, G1319V, identified in a BrS patient. The G1319V mutation is located in the loop connecting transmembrane segments 4 and 5 in domain III (DIIIS4-S5), a region so far considered to be exclusively involved in fast inactivation. METHODS: Whole-cell mutant (G1319V) and wild-type (WT) sodium currents (I(Na)) were studied in the Human Embryonic Kidney cell line (HEK-293) transfected with Na(v)1.5 alpha-subunit cDNA (WT or mutant) together with h beta(1)-subunit cDNA, using the patch-clamp technique. RESULTS: Maximal peak I(Na) and persistent sodium current were similar in WT and channel G1319V channels. The G1319V mutation shifted the potential of half maximal (V(1/2)) activation towards more positive potentials (+3.7 mV), thereby increasing the degree of depolarization required for activation. The V(1/2) of inactivation of G1319V channels was shifted by -6.0 mV compared to WT, resulting in a reduced channel availability. The change in the steady-state inactivation was completely due to a negative shift (-6.8 mV) of the voltage-dependence of slow inactivation, while the voltage-dependence of fast inactivation was unaffected. The fast component of recovery from inactivation of G1319V channels was slowed down. Finally, the G1319V mutation caused a two-fold increase in the propensity of the channels to enter the slow inactivated state. Reduction in I(Na) peak amplitude on repetitive depolarizations at short interpulse intervals (40 ms) was significantly more pronounced in G1319V compared to WT. Accordingly, carriers of the G1319V mutation showed marked QRS widening upon increases in heart rate during exercise testing, pointing to enhancement of slow inactivation. CONCLUSIONS: We identified the DIIIS4-S5 linker as a new region involved in slow inactivation of Na(v)1.5. The biophysical alterations of the G1319V mutation all contribute to a reduction in I(Na), in line with the proposed mechanism underlying BrS. PMID- 17854787 TI - Expression of securin promotes colorectal cancer cell death via a p53-independent pathway after radiation. AB - Securin has been shown to regulate genomic stability; nevertheless, the role of securin on the cytotoxicity after radiation is still unclear. Exposure to 1-10 Gy X-ray radiation induced cell death in RKO colorectal cancer cells. The protein levels of securin, p53, and p21 were elevated by radiation. The proteins of phosphorylation of p53 at serine-15, which located on the nuclei of cancer cells, were highly induced by radiation. However, radiation increased securin proteins, which located on both of nuclei and cytoplasma in RKO cells. The p53-wild type colorectal cancer cells were more susceptible on cytotoxicity than the p53-mutant cells following exposure to radiation. Besides, the existence of securin in colorectal cancer cells induced higher apoptosis than the securin-null after radiation. Securin proteins were elevated by radiation in the p53-wild type and mutant cells; furthermore, radiation raised the p53 protein expression in both the securin-wild type and -null cells. As a whole, these findings suggest that the existence of securin promotes apoptosis via a p53-indpendent pathway after radiation in human colorectal cancer cells. PMID- 17854788 TI - Arjunolic acid, a triterpenoid saponin, ameliorates arsenic-induced cyto-toxicity in hepatocytes. AB - Arsenic is a well-established environmental toxin, which damages various organs of the body. A triterpenoid saponin, arjunolic acid (AA) has been isolated from the bark of Terminalia arjuna. The present study was conducted to investigate the preventive role of AA against arsenic-induced cytotoxicity in isolated murine hepatocytes. Sodium arsenite (NaAsO(2)) was chosen as the source of arsenic. Incubation of the hepatocytes with NaAsO(2) (1 mM) for 2 h caused reduction in the cell viability and activities of the intracellular enzymatic as well as non enzymatic antioxidants. Treatment of NaAsO(2) enhanced lipid peroxidation and also increased the activities of the membrane leakage enzymes. Administration of AA (100 microg/ml) before and with the toxin almost normalized the altered activities of antioxidant indices. AA possesses free radical scavenging activity and could enhance the cellular anti-oxidant capability against NaAsO(2)-induced cyto-toxicity. The cytoprotective activity of AA was found to be comparable to that of a known antioxidant, vitamin C. Experimental results, therefore, suggest that AA protects arsenic-induced cytotoxicity in murine hepatocytes. PMID- 17854789 TI - Comparing pharmacokinetic and pharmacodynamic profiles in female rats orally exposed to lovastatin by gavage versus diet. AB - The objective of this study was to assess how the dosing method (i.e., gavage versus diet) affects the absorption and disposition of lovastatin, as well as its effect on two biological markers of exposure, such as serum levels of cholesterol and triglycerides. In preclinical safety studies the test agent is normally administered by gavage, but in chemoprevention efficacy studies the test agent is usually administered with the diet. Therefore, extrapolation of safety and efficacy data from laboratory animals to humans should consider the influence of the method of administration on the absorption, disposition and effect of the drug. Lovastatin, a blood cholesterol-lowering drug with a short elimination half life in humans, was used to assess the influence of two different dosing methods on the drug pharmacokinetics and pharmacodynamics. Plasma and liver concentrations of lovastatin and its active metabolite lovastatin-Na were measured in female rats at sequential times after administration. Serum concentrations of triglycerides and cholesterol were measured at similar times and used as biomarkers of effect. Significant differences in pharmacokinetics and pharmacodynamics were observed after administration of lovastatin by the two oral dosing paradigms. In general, oral gavage resulted in higher peak and lower trough concentrations of lovastatin and lovastatin-Na in plasma and liver, lower area under the concentration-time curve of lovastatin-Na in plasma and liver, and less of an effect on the serum concentrations of triglycerides and cholesterol than the corresponding diet dosing. Although no inverse linear relationship was observed between pharmacokinetic and pharmacodynamic markers, in the case of serum cholesterol a visual trend could be observed which might have proven significant had data from a larger number of dose levels been available. As in our previous study with sulindac, this study illustrates potential limitations in trying to extrapolate from data obtained using different dosing schemes to potential safety and efficacy in humans. PMID- 17854790 TI - Multi-center validation of the Response Biomedical Corporation RAMP NT-proBNP assay with comparison to the Roche Diagnostics GmbH Elecsys proBNP assay. AB - BACKGROUND: NT-proBNP measurements aid in the evaluation of patients with suspected heart failure (HF) and may facilitate risk stratification in patients with HF and acute coronary syndrome (ACS). Point-of-care (POC) assays may provide more timely results and potentially improve patient outcomes. METHODS: We evaluated the analytical performance of the Response Biomedical Corporation whole blood RAMP amino-terminal pro-B type natriuretic peptide (NT-proBNP) POC assay compared to the Roche Elecsys proBNP (NT-proBNP) assay. RESULTS: Intra-day and total imprecision (% CV) ranged from 5.5% to 10.3% at 140, 449 and 1675 ng/L. The lowest concentration that yields a 20% CV was 57 ng/L. The lower limit of detection was 18 ng/L. The upper limit of linearity was validated to 23,428 ng/L with an average recovery of 95%. Correlation by Passing and Bablok regression yielded RAMP=1.01 Elecsys+14.6, r=0.98 (n=540; range of Elecsys values <5 to >35,000). Concordance of RAMP versus Elecsys using cut-offs of 125 ng/L for subjects <75 years and 450 ng/L for subjects > or =75 was 92% (95% CI 89-94%) for a group consisting of 127 apparently healthy individuals and 208 non-healthy subjects without HF, and 99% (95% CI 97-100%) for patients with HF, using the New York Heart Association (NYHA) functional classification. Overall, 80%, 87%, 97% and 100% of the RAMP results and 77%, 85%, 96% and 100% of the Elecsys results were greater than the age appropriate cut-off for NYHA I, II, III or IV groups. For both the RAMP and Elecsys results, the median NT-proBNP value was statistically correlated (increasing) with NYHA I, II, III or IV groups, respectively (p<0.0001), with no significant difference between the two methods. CONCLUSIONS: The POC Response Biomedical RAMP NT-proBNP assay provides comparable results that measured on the FDA cleared Roche Elecsys central laboratory platform. PMID- 17854791 TI - A 60-y-old chylomicronemia patient homozygous for missense mutation (G188E) in the lipoprotein lipase gene showed no accelerated atherosclerosis. AB - BACKGROUND: Familial lipoprotein lipase (LPL) deficiency is a rare autosomal recessive disorder caused by mutations in the LPL gene. Patients with LPL deficiency have chylomicronemia; however, whether they develop accelerated atherosclerosis remains unclear. METHODS: We investigated clinical and mutational characteristics of a 60-y-old Japanese patient with chylomicronemia. RESULTS: The patient's fasting plasma triglyceride levels were >9.0 mmol/l. In postheparin plasma, one fifth of the normal LPL protein mass was present; however, LPL activity was undetectable. Molecular analysis of the LPL gene showed the patient to be a homozygote of missense mutation replacing glycine with glutamine at codon 188 (G188E), which had been known to produce mutant LPL protein lacking lipolytic activity. Ultrasonographic examination of the patient's carotid and femoral arteries showed no accelerated atherosclerosis. Moreover, 64-slice mechanical multidetector-row computer tomography (MDCT) angiography did not detect any accelerated atherosclerotic lesions in the patient's coronary arteries. The patient had none of the risk factors such as smoking, hypertension, and diabetes. CONCLUSIONS: Our case suggests that accelerated atherosclerosis may not develop in patients with LPL deficiency, when they have no risk factors. PMID- 17854792 TI - Quantification of urinary 8-iso-PGF2alpha using liquid chromatography-tandem mass spectrometry and association with elevated troponin levels. AB - OBJECTIVES: Increased lipid peroxidation (i.e. "oxidative stress") has been identified as a central mechanism in the development of atherosclerosis and inflammatory vascular damage. Measurement of 8-iso-PGF(2alpha) has demonstrated to be a reliable indicator of in vivo oxidative stress levels. The purpose of this study was to develop a rapid, sensitive, and specific LC-MS/MS method for detection of urinary 8-iso-PGF(2alpha), establish reference intervals, and correlate isoprostane levels with cardiac troponin I. DESIGN AND METHODS: Urinary 8-iso-PGF(2alpha) was detected after direct injection onto a C18 silica column and monitored in the MRM mode using m/z transitions of 353.2>193.25 (8-iso PGF(2alpha)) and 357.2>197.25 (8-iso-PGF(2alpha)-d(4)). The LC-MS/MS method was also compared to an ELISA kit. Reference interval studies were evaluated against a separate population of patients presenting with chest pain that had positive cTnI values. RESULTS: Elution of 8-iso-PGF(2alpha) was achieved after 7 min, with a total run time of 10 min. Inter-assay CVs were 13.8-20.0% and intra-assay CVs were 10.9-17.0%. Linearity ranged from 100 pg/mL to 100 ng/mL. Deming regression of ELISA and LC-MS/MS methods for 8-iso-PGF(2alpha) levels yielded poor correlation, with a slope of 0.0265, y-intercept of 0.255 ng/mL, and R(2) value of 0.0434. Urine 8-iso-PGF(2alpha) concentrations in samples obtained from healthy individuals (n=34) ranged from 57 to 390 ng/g creatinine with a mean of 221 ng/g creatinine. 8-iso-PGF(2alpha) levels were statistically significant in troponin-positive (n=35) versus troponin-negative (n=36) patients (p<0.0049). CONCLUSIONS: This LC-MS/MS method provides a rapid, accurate, sensitive, and cost effective alternative to other methods for detection of 8-iso-PGF(2alpha) in urine. 8-iso-PGF(2alpha) has potential to be a great prognostic risk indicator in individuals with a high probability for future coronary events. PMID- 17854793 TI - Real-time PCR genotyping of aldehyde dehydrogenase-2 using displacing probes. AB - OBJECTIVES: This study aimed to develop and validate a rapid, accurate method for aldehyde dehydrogenase-2 gene (ALDH2) genotyping. DESIGN AND METHODS: We reported a single-tube, real-time PCR method for ALDH2 allele detection using two displacing probes. RESULTS: The genotyping results of 136 human genomic DNA samples indicated 100% concordance between real-time PCR method and the PCR-RFLP analysis. CONCLUSIONS: The developed method could be used for routine clinical testing and high throughput genetic screening of ALDH2. PMID- 17854794 TI - Automatic determination of ligand purity and apparent dissociation constant (K(app)) in Ca(2+)/Mg(2+) buffer solutions and the K(app) for Ca(2+)/Mg(2+) anion binding in physiological solutions from Ca(2+)/Mg(2+)-macroelectrode measurements. AB - Calibration of Ca(2+)/Mg(2+) macroelectrodes and flurochromes in the nmolar and mumolar range, respectively, require the use of buffer solutions. In these buffers the apparent dissociation constant (K(app)) has to be measured since calculation based on tabulated constants gives variable results. The ligand concentration [Ligand](T) has also to be estimated. The most accurate and general method for measuring both is the ligand optimisation method based on macroelectrode potential measurements, but this iterative method is time consuming, thus limiting its application. This paper describes an automatic program based on the method, which on entering the measured macroelectrode data calculates K(app), [Ligand](T) and the ionised concentration [X(2+)] within minutes. This optimisation method cannot be used at K(app) values greater than 0.1mM, but can be extended into this region if the anion concentration is known. The program has been modified to cover this eventuality. Ca(2+)/Mg(2+) macroelectrodes in conjunction with these programs offer an accurate, routine method for determining K(app) and [Ligand](T) in buffer solutions at the appropriate ionic strength, temperature and pH and the K(app) for divalent cations binding to physiological anions under experimental conditions. PMID- 17854795 TI - Breast MR segmentation and lesion detection with cellular neural networks and 3D template matching. AB - A novel fully automated system is introduced to facilitate lesion detection in dynamic contrast-enhanced, magnetic resonance mammography (DCE-MRM). The system extracts breast regions from pre-contrast images using a cellular neural network, generates normalized maximum intensity-time ratio (nMITR) maps and performs 3D template matching with three layers of 12x12 cells to detect lesions. A breast is considered to be properly segmented when relative overlap >0.85 and misclassification rate <0.10. Sensitivity, false-positive rate per slice and per lesion are used to assess detection performance. The system was tested with a dataset of 2064 breast MR images (344slicesx6 acquisitions over time) from 19 women containing 39 marked lesions. Ninety-seven percent of the breasts were segmented properly and all the lesions were detected correctly (detection sensitivity=100%), however, there were some false-positive detections (31%/lesion, 10%/slice). PMID- 17854796 TI - Selenium as a potential protective factor against mercury developmental neurotoxicity. AB - Experimental studies suggest that selenium (Se) may decrease methylmercury (MeHg) toxicity under certain exposure regimens. In epidemiological studies, the exposure to MeHg occurs from fish and seafood, which are also a source of beneficial nutrients such as selenium. However, little is known about the potential protective effects of dietary Se against MeHg neurotoxicity in humans. The possible interaction was assessed in two birth cohorts in the Faroe Islands, consisting of singleton term births from 1986 to 1987 (N=1,022), and 1994 to 1995 (N=182), respectively. Dietary habits in this fishing population included frequent consumption of seafood, including whale meat high in mercury. Both Hg and Se were measured in cord whole blood. Neurodevelopmental outcomes were evaluated at age 7 years in both cohorts, and the smaller cohort also included neurological assessment on several prior occasions. Each outcome was modeled as a function of Hg and Se interactions (with adjustments for potential risk factors) by expressing the effects of log10(Hg) within the lowest 25%, the middle 50%, and the highest 25% of the Se distribution. Surplus Se was present in cord blood, the average being a 10-fold molar excess above MeHg. Regression analyses failed to show consistent effects of Se, or statistically significant interaction terms between Se and MeHg. Overall, no evidence was found that Se was an important protective factor against MeHg neurotoxicity. Prevention, therefore, needs to address MeHg exposures rather than Se intakes. Because of the benefits associated with fish intake during pregnancy, consumers should be advised to maintain a high fish and seafood intake that is low in Hg contamination. Additional research is needed to determine the identity of the nutrients responsible for the beneficial effects. PMID- 17854797 TI - Beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats. AB - As glucocorticoids influence both catecholamine synthesis and adrenoceptor expression by immune cells, the current study was undertaken to distinguish their direct effects on the development of experimental allergic encephalomyelitis from those induced by alteration of catecholamine signaling. We examined the influence of 16-day-long beta-adrenoceptor blockade with propranolol (0.40 mg/100 g body weight/day, s.c.) beginning 3 days before immunization on the development of experimental allergic encephalomyelitis in adrenalectomized (7 days before immunization) and in non-operated male Dark Agouti rats. Adrenalectomy aggravated the clinical course of experimental allergic encephalomyelitis. In contrast, propranolol attenuated both the clinical signs of the disease and decreased the number of lesions in the spinal cord. Furthermore, propranolol prevented adrenalectomy-induced aggravation of the disease course without affecting mortality. We also found that the percentage of CD4(+)CD25(+) T lymphocytes (recently activated or regulatory cells) was increased in peripheral blood of experimental allergic encephalomyelitis rats over that in the corresponding non immunized and bovine serum albumin immunized rats. However, the percentage of these cells was reduced in adrenalectomized and/or propranolol-treated experimental allergic encephalomyelitis rats compared to control experimental allergic encephalomyelitis rats. Our findings, coupled with the clinical course of the disease and the underlying pathomorphological changes, clearly suggest that differential mechanisms were responsible for the changes in the percentage of CD4(+)CD25(+) T lymphocytes in propranolol-treated adrenalectomized rats and only propranolol-treated rats with experimental allergic encephalomyelitis. Our results, when viewed globally, indicate that: i) beta-adrenoceptor-dependent mechanisms are involved in the immunopathogenesis of experimental allergic encephalomyelitis, ii) experimental allergic encephalomyelitis has a more severe course in adrenalectomized rats and iii) beta-adrenoceptor-mediated mechanisms operate in adrenalectomy-induced aggravation of the disease. PMID- 17854798 TI - Induction of Nrf2-regulated genes by 3H-1, 2-dithiole-3-thione through the ERK signaling pathway in murine keratinocytes. AB - Electrophile and free radical detoxifying enzymes including NAD(P)H:quinine oxidoreductase 1 (Nqo1) play an important role in the defense system by enhancing cellular antioxidant capacity. Chemopreventive efficacy of 3H-1,2-dithiole-3 thione (D3T) is mediated through activation of the transcription factor Nrf2 and subsequent elevation of detoxifying enzymes. In the present study, we have investigated the potential role of extracellular signal-regulated kinase (ERK) in regulation of D3T-induced and Nrf2-dependent gene expression in murine keratinocytes. Expression levels of Nqo1 were highly inducible by D3T treatment and increased nuclear levels of Nrf2 were observed in these cells. Treatment with pharmacological inhibitor of ERK1/2 largely blocked nuclear accumulation of Nrf2, ARE-driven reporter gene expression, and induction of Nqo1, as well as other phase 2 genes. Activation of ERK1/2 has been demonstrated following treatment with D3T. While, inhibitors of p38, PKC and PI3K did not affect ARE-driven gene expression. Involvement of the ERK1/2 cascade in inducible ARE-transcription activities was also observed in cells treated with other types of inducers oltipraz, sulforaphane and hydrogen peroxide. Collectively, current study suggests that phosphorylation cascade via ERK1/2 is associated with the activation process of Nrf2 and subsequent transactivation of its target gene Nqo1 following treatment with dithiolethione in murine keratinocyte. PMID- 17854799 TI - WAY-100635 has high selectivity for serotonin 5-HT(1A) versus dopamine D(4) receptors. AB - The serotonin 5-HT(1A) receptor antagonist WAY-100635 was recently reported to have potent agonist properties at dopamine D(4) receptors (Chemel et al., 2006, Psychopharmacology 188, 244-251.). Herein WAY-100635 (pK(i) at human (h) serotonin 5-HT(1A) receptors=9.51; pK(i) at dopamine hD(4.4) receptors=7.42) stimulated [(35)S]GTPgammaS incorporation in membranes of Chinese Hamster Ovary cells expressing dopamine hD(4.4) receptors with only moderate potency and modest efficacy (pEC(50)=6.63; E(max)=19% of dopamine). Moreover, in antagonism experiments, WAY-100635 had a much lower potency at dopamine hD(4.4) receptors (pK(B)=7.09), than at serotonin h5-HT(1A) receptors (pK(B)=9.47). These data demonstrate that WAY-100635 has high selectivity for serotonin h5-HT(1A)versus dopamine hD(4.4) receptors. PMID- 17854800 TI - Divergent effect of proteasome inhibition on interleukin-1beta and tumor necrosis factor alpha signaling in human astroglial cells. AB - Impaired functioning of the proteasome pathway is one of the molecular mechanism underlying neurodegenerative changes in Alzheimer's disease. In this study, we report that dysfunction of the proteasome pathway in astroglial cells leads to decreased survival and dysregulation of chemokines by differential regulation of the nuclear factor kappa B and c-jun N-terminal kinase (JNK) pathways. We further demonstrated that proteasome inhibition augmented interleukin-1 beta- and tumor necrosis factor-alpha-induced activation of the IkappaBalpha kinase and MKK4/JNK/c-Jun pathway along with TAK1 activation. These results suggest that impaired function of the proteasome pathway may potentiate the immuno-pathologic role of secondarily activated astrocytes in the brain. PMID- 17854801 TI - Two neighboring residues of loop A of the alpha1 subunit point towards the benzodiazepine binding site of GABAA receptors. AB - Benzodiazepines are widely used drugs exerting sedative, anxiolytic, muscle relaxant, and anticonvulsant effects by acting through specific high affinity binding sites on some GABA(A) receptors. It is important to understand how these ligands are positioned in this binding site. We are especially interested here in the conformation of loop A of the alpha(1)beta(2)gamma(2) GABA(A) receptor containing a key residue for the interaction of benzodiazepines: alpha(1)H101. We describe a direct interaction of alpha(1)N102 with a diazepam- and an imidazobenzodiazepine-derivative. Our observations help to better understand the conformation of this region of the benzodiazepine pocket in GABA(A) receptor. PMID- 17854802 TI - Post-translational modification of barley LTP1b: the lipid adduct lies in the hydrophobic cavity and alters the protein dynamics. AB - NMR techniques have been used to characterise the effects of a lipid-like post translational modification on barley lipid transfer protein (LTP1b). NMR chemical shift data indicate that the lipid-like molecule lies in the hydrophobic cavity of LTP1b, with Tyr 79 being displaced to accommodate the ligand in the cavity. The modified protein has a reduced level of backbone amide hydrogen exchange protection, presumably reflecting increased dynamics in the protein. This may result from a loosening of the protein structure and may explain the enhanced surface properties observed for LTP1b. PMID- 17854803 TI - Linking membrane microdomains to the cytoskeleton: regulation of the lateral mobility of reggie-1/flotillin-2 by interaction with actin. AB - The reggies/flotillins are oligomeric scaffolding proteins for membrane microdomains. We show here that reggie-1/flotillin-2 microdomains are organized along cortical F-actin in several cell types. Interaction with F-actin is mediated by the SPFH domain as shown by in vivo co-localization and in vitro binding experiments. Reggie-1/flotillin-2 microdomains form independent of actin, but disruption or stabilization of the actin cytoskeleton modulate the lateral mobility of reggie-1/flotillin-2 as shown by FRAP. Furthermore, reggie/flotillin microdomains can efficiently be immobilized by actin polymerisation, while exchange of reggie-1/flotillin-2 molecules between microdomains is enhanced by actin disruption as shown by tracking of individual microdomains using TIRF microscopy. PMID- 17854804 TI - Macrophage migration inhibitory factor (MIF) promotes fibroblast migration in scratch-wounded monolayers in vitro. AB - MIF was recently redefined as an inflammatory cytokine, which functions as a critical mediator of diseases such as septic shock, rheumatoid arthritis, atherosclerosis, and cancer. MIF also regulates wound healing processes. Given that fibroblast migration is a central event in wound healing and that MIF was recently demonstrated to promote leukocyte migration through an interaction with G-protein-coupled receptors, we investigated the effect of MIF on fibroblast migration in wounded monolayers in vitro. Transient but not permanent exposure of primary mouse or human fibroblasts with MIF significantly promoted wound closure, a response that encompassed both a proliferative and a pro-migratory component. Importantly, MIF-induced fibroblast activation was accompanied by an induction of calcium signalling, whereas chronic exposure with MIF down-regulated the calcium transient, suggesting receptor desensitization as the underlying mechanism. PMID- 17854805 TI - Comparison of urinary and recombinant follicle-stimulating hormone in in vitro growth, maturation, and fertilization of mouse preantral follicles. AB - OBJECTIVE: To compare the effects of urinary and recombinant follicle-stimulating hormone (FSH) on follicular development, oocyte maturation, and fertilization. DESIGN: Prospective randomized animal study. SETTING: University-based research laboratory. ANIMAL(S): Normal (C57BL/6xDBA2) F1 mice. INTERVENTION(S): Collection of preantral follicles by mechanical dissection, in vitro growth (IVG) with urinary or recombinant FSH (100 mIU/mL), in vitro maturation (IVM), and fertilization. MAIN OUTCOME MEASURE(S): During IVG, follicle diameter and antral formation were evaluated. The number of cells per follicle was evaluated at the end of IVG. The 17beta-estradiol measurements were performed from conditioned media. After IVM, mucification and oocyte maturation rates were estimated and mature oocytes were fertilized. RESULT(S): No differences were observed in the antral formation rate of either group. Antral follicles in the urinary FSH group, however, showed a higher diameter but a lower number of cells per follicle than those in the recombinant FSH group. The level of 17beta-estradiol was also higher in the recombinant FSH group. The rate of mature oocytes developing into metaphase I or II was statistically significantly higher in the recombinant FSH group than in the urinary FSH group. CONCLUSION(S): Recombinant FSH provided better conditions than urinary FSH for the growth and development of mouse preantral follicles that could produce mature oocytes with fertilization capacity. PMID- 17854807 TI - An improved auto-tuning scheme for PI controllers. AB - Ziegler-Nichols tuned PI and PID controllers are usually found to provide poor performances for high-order and nonlinear systems. In this study, an improved auto-tuning scheme is presented for Ziegler-Nichols tuned PI controllers (ZNPICs). With a view to improving the transient response, the proportional and integral gains of the proposed controller are continuously modified based on the current process trend. The proposed controller is tested for a number of high order linear and nonlinear dead-time processes under both set-point change and load disturbance. It exhibits significantly improved performance compared to ZNPIC, and Refined Ziegler-Nichols tuned PI controller (RZNPIC). Robustness of the proposed scheme is established by varying the controller parameters as well as the dead-time of the process under control. PMID- 17854806 TI - Cellular localisation of the pregnancy-associated glycoprotein family (PAGs) in the synepitheliochorial placenta of the European bison. AB - This paper describes the cellular immuno-localisation of the PAG family in synepitheliochorial (cotyledonary) placenta of the European bison (Eb). Uteri were harvested from pregnant wild Eb (n=4; 45-150 days post coitum-dpc); and additionally from cattle (30, 45 dpc) and pigs (42 dpc)--both domestic species were used as positive controls for cellular PAG immunodetection. Placentas were sectioned, fixed, dehydrated and subjected to double fluorescent immunohistochemistry (dF-IHC) with the use of Alexa 488 fluorochrom (A488) and propidium iodide (PI). Native positive EbPAG signals were detected by heterologous (ht; cross-species) dF-IHC with primary rabbit anti-PAG polyclonals against native or recombinant porcine PAG antigens (anti-pPAG); then visualised with secondary anti-rabbit goat immunoglobulins--conjugated to A488. Our htdF-IHC indicated an unequivocal localisation to the mono- and bi-nuclear trophectoderm (chorionic epithelium) cells expressing the PAGs (A488-green) among all placental cells, in which PI (red) stained nuclei. This is the first paper reporting the EbPAG family expression examined by htdF-IHC at the feto-maternal interface in wild Pecoran species. The cross-reactivity of anti-pPAG polyclonals with the EbPAGs suggests that shared epitopes are present in these molecules. It seems that the EbPAG family, which is robustly expressed in mono- and bi-nucleated trophectoderm cells, is associated with events taking place during placenta development. Our study also provided a proficient ht-system to identify various PAGs that could be useful as prenatal protein markers for pregnancy diagnoses, which is essential for effective reproductive management of endangered mammals. PMID- 17854808 TI - Strengthening public health priority-setting through research on fistula, maternal health, and health inequities. AB - OBJECTIVE: Findings from 4 studies conducted by the Women's Dignity Project and partners on the subjects of obstetric fistula, maternal mortality and morbidity, and health inequities are presented. METHODS: The studies include qualitative and quantitative research, a survey, and an analysis of secondary data that examine women's experiences of fistula; constraints in service delivery for fistula treatment; factors shaping women's access to delivery care and constraints health workers face in providing care; and health inequities. RESULTS: Findings from the studies are being used to improve fistula prevention and management, strengthen access to and provision of quality maternity care, and redress the health inequities that so adversely affect the poor. CONCLUSION: The studies provide policy makers, program managers, and service providers with evidence and the impetus to re-equilibrate policies, financial and human resources, and services in the interest of those in greatest need: women living in poverty. PMID- 17854809 TI - Delay in seeking treatment and adherence to tuberculosis medications in Russia: a survey of patients from two clinics. AB - BACKGROUND: Tuberculosis is a global problem, especially in high burden countries such as Russia, that is fueled by delay in seeking treatment and nonadherence to prescribed medications. Stigma and illness representation (a person's mental image of a specific illness) have the potential to affect treatment seeking and adherence. OBJECTIVES: To describe the illness representation of tuberculosis in Russians with active pulmonary tuberculosis, and to determine if stigma and illness representation are predictors of delay in seeking treatment and adherence to tuberculosis medications. DESIGN: Cross-sectional, descriptive survey. SETTING: Two outpatient clinics in the Vladimir Region, Russia. PARTICIPANTS: A total of 105 adults, 18 years and older, being treated for active pulmonary tuberculosis, and on outpatient therapy for a minimum of four weeks participated in this study. METHODS: Delay was measured with a question asking length of time between onset of symptoms and appointment with a physician. Stigma was measured using the Social Impact Scale. Illness representation was measured using the Revised Illness Perception Questionnaire. Participants' outpatient medication records were reviewed for medication adherence. RESULTS: Symptoms reported were not consistent with those described in the medical literature and other studies. Only four subjects suspected tuberculosis based on their symptoms; 60% believed they had other respiratory infections. Multiple regression showed that illness identity (an attribute of illness representation) (beta=0.23) was a significant predictor of delay, accounting for 29% of the variance (p=0.008); and financial insecurity (beta=-0.28) and internalized shame (beta=0.27) (measures of stigma) were both significant predictors of medication adherence, accounting for 23% of the variance (p=0.003). CONCLUSIONS: Illness identity was associated with delay. Internalized shame was associated with increased medication adherence while financial insecurity was associated with decreased adherence. Results point to the need for broad, culturally specific patient, family, and community education programs. PMID- 17854810 TI - Mixed Giardia duodenalis assemblage A and E infections in calves. AB - A molecular epidemiological study was conducted on 100 dairy (499 calves) and 50 beef (333 calves) farms in Belgium to estimate the prevalence of different Giardia duodenalis assemblages in calves younger than 10 weeks of age. Positive samples from the epidemiological study and from a previous clinical study were selected and genotyped based on the amplification of the beta-giardin gene. To investigate the occurence of mixed assemblage A and E infections in calves, a novel assemblage-specific PCR was developed based on the triose-phosphate isomerase gene. The prevalence was 22% (95% Probability Interval (PI): 12-34%) in dairy calves and 45% (95% PI: 30-64%) in beef calves. In total, 120 Giardia positive samples from dairy and beef calves collected in the epidemiological study and from clinically affected calves were identified based on the amplification of the beta-giardin gene. Overall G. duodenalis assemblage E was more prevalent (in 64% of the samples), although the majority (59%) of the dairy calves were infected with G. duodenalis assemblage A. Furthermore, mixed G. duodenalis assemblage A and E infections were identified in 31% of the calf samples (n=101) using the assemblage-specific PCR. We believe this is the first report of mixed infections in calves, and the results of the present study indicate that calves, although mainly infected with the host-specific G. duodenalis assemblage E, are frequently infected with the zoonotic assemblage A, either as a mixed or mono-infection, suggesting that calves might be underestimated as a potential zoonotic reservoir for human infections. PMID- 17854811 TI - Renal function and metabolic syndrome components on cardiovascular and all-cause mortality. AB - OBJECTIVES: Impaired renal function and metabolic syndrome have been associated with risk of cardiovascular disease (CVD). We investigated their roles in CVD and all-cause death among ethnic Chinese population. METHODS: We followed up a cohort of 11429 men and 7472 women aged 20 years and older for an average 4.9 years (median: 3.5, inter-quartile range: 2.7-7.9) from the tertiary hospital health check-up population. RESULTS: CVD death rates increased when the quintiles of each variable progressed. Metabolic syndrome was a significant predictor for CVD death, with relative risk of up to 4.68. In the multivariate adjusted model that included metabolic syndrome, quintiles of serum creatinine concentrations, estimated glomerular filtration rate (GFR), and uric acids were significantly associated CVD death, with the highest relative risk of creatinine concentration (11.22, 95% confidence interval [CI]: 2.43-51.7, P for trend: <0.001). Serum creatinine concentrations and estimated GFR had the higher areas under ROC curves of CVD death (0.76, 95% CI: 0.71-0.80 for creatinine and 0.76, 95% CI: 0.72-0.81 for estimated GFR). The two marker models showed that metabolic syndrome and impaired renal function had the most significant roles in predicting CVD deaths; the multivariate relative risk was 30.6 (95% CI: 3.7-254, P: 0.002) in participants with the highest creatinine and presence of metabolic syndrome compared with those with the lowest and absence of metabolic syndrome. CONCLUSIONS: Impaired renal function and metabolic syndrome are important risk factors for CVD and all-cause deaths among ethnic Chinese. PMID- 17854812 TI - Squalene in a sex-dependent manner modulates atherosclerotic lesion which correlates with hepatic fat content in apoE-knockout male mice. AB - BACKGROUND: Squalene is an intermediate of cholesterol biosynthesis which can be obtained from the diet where it is abundant, for example, in olive oil. The effect of this isoprenoid on the development of atherosclerosis was investigated on apoE-knockout mice. METHODS AND RESULTS: Two groups of animals, separated according to sex, were fed on standard chow diet: the control group receiving only vehicle and the second group an aqueous solution of squalene to provide a dose of 1g/kg/day in male and female mice. This treatment was maintained for 10 weeks. At the end of this period, plasma lipid parameters, oxidative stress markers and hepatic fat were measured as well as cross-sectional lesion area of aortic root in both groups. Data showed that in males squalene feeding reduced atherosclerotic lesion area independently of plasma lipids and activation of circulating monocytes. In contrast, squalene intake did not decrease lesion area in females, despite reducing plasma cholesterol and triglycerides, isoprostane and percentage of Mac-1 expressing white cells. In males, atherosclerotic lesion area was positively and significantly associated with hepatic fat content and the plasma triglycerides were also strongly associated with liver weight. CONCLUSIONS: These results indicate that administration of squalene modulates lesion development in a gender specific manner, and that accumulation of hepatic fat by liver is highly correlated with lesion progression in males. Hence, squalene administration could be used as a safe alternative to correct hepatic steatosis and atherosclerosis particularly in males. PMID- 17854814 TI - Asymmetric development of peripheral atherosclerosis in patients with erectile dysfunction: an ultrasonographic study. AB - Recent literature focused on erectile dysfunction (ED) as a reliable predictive parameter of cardiovascular diseases. ED patients have a higher prevalence of atherosclerotic lesions (increased intima-media thickness and plaques) at carotid site, but data on femoral site are still lacking. Nevertheless, there is accumulating evidence concerning a significant involvement of femoral atherosclerosis in other clinical conditions associated to ED, such as diabetes mellitus and coronary disease. Therefore, we investigated the prevalence of carotid and femoral atherosclerotic lesions and penile peak systolic velocity (PSV) in 238 ED patients by Eco-Colour Doppler ultrasonography (US). We found - irrespective of the presence of cardiovascular risk factors - a significant increase of atherosclerotic lesions in ED group with respect to 52 controls (66.4% versus 36.5%) and a higher prevalence of atherosclerosis at the femoral site (23.1% versus 5.7%), also with respect to the carotid site (8%). Moreover, PSV was significantly lower in ED patients with atherosclerosis compared to those without atherosclerotic lesions (41.9+/-15.3 cm/s versus 55.2+/-17.7 cm/s), and it was particularly low in those with combined carotid and femoral atherosclerosis (34.8+/-13.3 cm/s) and those with isolated carotid atherosclerosis (37.9+/-13.0 cm/s). These data confirm the strong relation between atherosclerosis and ED, an asymmetric development of atherosclerotic lesions in ED patients and suggest to perform an US study of both femoral and carotid district in these subjects. PMID- 17854813 TI - Socioeconomic status moderates the association between carotid intima-media thickness and cognition in midlife: evidence from the Whitehall II study. AB - BACKGROUND: Common carotid artery intima-media thickness (IMT) is a measure of generalized atherosclerosis and has been shown to be associated with cognitive function. We examine two questions: does socioeconomic status (SES) moderate this association and is IMT more strongly associated with specific aspects of cognitive function? METHODS: Data are drawn from the Phase 7 (2003-2004) of the Whitehall II study (N=3896). In cross-sectional analyses the association between IMT and six measures of cognition (short-term verbal memory, inductive reasoning, vocabulary, semantic and phonemic fluency and a measure of global cognitive status) was examined in analyses adjusted for previous history of coronary heart disease, health behaviours and other vascular risk measures such as blood pressure, cholesterol and body mass index. RESULTS: The overall association between IMT and the six measures of cognition was restricted to the low SES group (p=0.02). Within this group, IMT was significantly associated with inductive reasoning (p=0.001), vocabulary (p=0.002), phonemic (p=0.006) and semantic fluency (p=0.02). The covariates examined explained about a quarter of the association between IMT and cognition in the low SES group. The associations with the measure of inductive reasoning (p=0.02), vocabulary (p=0.02) and phonemic fluency (p=0.04) remained after adjustment for all covariates. CONCLUSIONS: SES is an important modifier of the association between IMT and cognition, an inverse association between the two was observed only in the low SES group. It is possible that high cognitive reserve among the high SES individuals prevents the functional manifestations of atherosclerosis. Verbal memory was not one of the cognitive domains associated with IMT. PMID- 17854815 TI - A method for in-vivo kinematic analysis of the forearm. AB - PURPOSE: To develop a method for in-vivo kinematic study of normal forearm rotation using computed tomographic (CT) images and a custom apparatus which allows for control of amount of forearm rotation. METHODS: The forearm of one asymptomatic volunteer was CT-scanned in five positions: neutral, 60 degrees pronation, maximal pronation, 60 degrees supination, and maximal supination. Surface registration of the pronated/supinated image datasets with the neutral position was performed. The resulting transformation matrices were decomposed into finite helical axis (FHA) parameters. Kinematics were expressed as motion of the radius relative to the ulna. RESULTS: The axes of the forearm passed through the volar region of the radial head at the proximal radioulnar joint (PRUJ), extending towards the dorsal region of the ulnar head at the distal radioulnar joint (DRUJ). Distinct FHAs were calculated for each forearm position analyzed relative to neutral rotation. Forearm pronation FHAs were different from forearm supination FHAs. CONCLUSIONS: Our experimental methodology is capable of describing the in-vivo kinematics of the forearm with good accuracy and reliability. Future in-vivo studies would need to be performed using a larger sample size to further validate our preliminary results. An ideal clinical application of this methodology would be in the comparative study of patients with forearm dysfunction. PMID- 17854816 TI - Fractal dimensions of pacing and grip force in drawing and handwriting production. AB - We performed a repeated measures experiment to show that the pacing of a cyclic, ballistic drawing task has a fractal dimension. We also estimated the dimensionality of the force used to grip the drawing implement. Finally, we present an analysis of pediatric data to show that grip force has a fractal dimension in an actual handwriting task. In our experiment, subjects drew circles of varying sizes and at varying rates on a digitizing tablet, using a pen instrumented to measure radial force applied to its barrel. Subjects also drew circles in synchrony with a metronome. We found strong evidence for fractal scaling of both drawing period and grip force in the circle-drawing study. The dimensionality ranged from fractal Gaussian noise (fGn) to fractal Brownian motion, with Hurst coefficients clustering around the value for 1/f noise. When the subjects were required to synchronize their drawing with a metronome, the Hurst coefficient for the drawing period decreased, while the coefficient for grip force did not. This result indicates that independent processes control the variations in pacing and grip force. Grip force in the handwriting study also displayed fractal properties, with Hurst coefficients in the range of correlated fGn. We draw parallels between our handwriting measurements and studies of human gait. PMID- 17854817 TI - Analysis of polynuclear aromatic hydrocarbons in heavy products derived from coal and petroleum by high performance liquid chromatography. AB - A systematic study was made on the identification and quantitative determination of polynuclear aromatic hydrocarbons (PAHs) in heavy products derived from coal and petroleum with high performance liquid chromatography (HPLC). After the separation of PAHs by a high-resolution column, identification was made through four methods: (1) the relative retention time (RRT) method, (2) the stop-flow-UV scanning method, (3) the method of fluorescence characteristic index Phi' and (4) the method of V' index at different UV wavelengths. For the quantitative determination of the components, methods of external standard (E-X), internal standard (I-N) and external standard-response factors (E-F) were compared. The E F method was recommended by the present paper. For the determination of quantitative response factors (F) two methods were studied, including the HPLC peak-area method (Peak-area method) and the UV absorbance method using a UV spectrometer (absorbance method). The absorbance method was better and is recommended by the present paper. The F values of 30 PAHs from the two different methods are given. The samples analyzed include a coal tar pitch, a thermal cracking residue oil and a residual oil from ethylene production. PMID- 17854818 TI - Appropriate volumes for adsorption isotherm studies: the absolute void volume, accessible pore volume and enclosing particle volume. AB - In adsorption studies the choice of an appropriate void volume in the calculation of the adsorption isotherm is very crucial. It is often taken to be the apparent volume as determined by the helium expansion experiments. Unfortunately this method has difficulties especially when dealing with microporous solids, in which adsorption of helium might become significant at ambient temperatures. The amount adsorbed is traditionally obtained as the excess amount and the term "excess" refers to the excess over the amount occupying the apparent volume that has the same density as the bulk gas density. This could give rise to the maximum in the plot of excess amount versus pressure under supercritical conditions, and in some cases giving negative excess. Such behavior is difficult to analyze because the excess amount is not amenable to any classical thermodynamic treatments. In this paper we will present a method to determine the absolute void volume, and in that sense this volume is independent of temperature and adsorbate. The volume that is accessible to the centers of gas molecules is also investigated, and it is called the accessible volume. This volume depends on the choice of adsorbate, and it is appropriate to use this volume to calculate the pore density because we can assess how dense the adsorbed phase is. In the quest to determine the "absolute" adsorption isotherm so that a thermodynamics analysis can be applied, it is necessary to introduce the concept of "enclosing" volume, which is essentially the volume that encloses all solid particles, including all void spaces in them. The amount adsorbed is defined by the number of molecules residing in this volume. Having these volumes, we can derive the geometrical accessible void volume inside the particle and the solid volume, from which the particle and solid densities can be calculated. PMID- 17854819 TI - A study of oil droplet coalescence. AB - Oil droplets dispersed in water can be readily studied when they are coated with surfactants, which lower their interfacial tension and enhance their stability. Pure oil droplets are more difficult to study because of their high interfacial tension, which facilitates coalescence and the adsorption of contaminants. In this study, we have characterised the surface charging properties of a water insoluble oil, bromododecane, which has a density close to water. The small density difference allows us to study relatively large drops of this oil and to analyse its coalescence behaviour. The results obtained with this simple, surfactant-free, system suggest that an additional attractive force, such as the long range hydrophobic interaction, might be required to explain oil droplet coalescence behaviour. PMID- 17854820 TI - Cryo-SEM studies of latex/ceramic nanoparticle coating microstructure development. AB - Cryogenic scanning electron microscopy (cryo-SEM) was used to investigate microstructure development of composite coatings prepared from dispersions of antimony-doped tin oxide (ATO) nanoparticles (approximately 30 nm) or indium tin oxide (ITO) nanoparticles (approximately 40 nm) and latex particles (polydisperse, D(v): approximately 300 nm). Cryo-SEM images of ATO/latex dispersions as-frozen show small clusters of ATO and individual latex particles homogeneously distribute in a frozen water matrix. In contrast, cryo-SEM images of ITO/latex dispersions as-frozen show ITO particles adsorb onto latex particle surfaces. Electrostatic repulsion between negatively charged ATO and negatively charged latex particles stabilizes the ATO/latex dispersion, whereas in ITO/latex dispersion, positively charged ITO particles are attracted onto surfaces of negatively charged latex particles. These results are consistent with calculations of interaction potentials from past research. Cryo-SEM images of frozen and fractured coatings reveal that both ceramic nanoparticles and latex become more concentrated as drying proceeds; larger latex particles consolidate with ceramic nanoparticles in the interstitial spaces. With more drying, compaction flattens the latex-latex particle contacts and shrinks the voids between them. Thus, ceramic nanoparticles are forced to pack closely in the interstitial spaces, forming an interconnected network. Finally, latex particles partially coalesce at their flattened contacts, thereby yielding a coherent coating. The research reveals how nanoparticles segregate and interconnect among latex particles during drying. PMID- 17854821 TI - Low working memory capacity impedes both efficiency and learning of number transcoding in children. AB - This study aimed to evaluate the impact of individual differences in working memory capacity on number transcoding. A recently proposed model, ADAPT (a developmental asemantic procedural transcoding model), accounts for the development of number transcoding from verbal form to Arabic form by two mechanisms: the learning of new production rules that enlarge the range of numbers a child can transcode and the increase of the mental lexicon. The working memory capacity of 7-year-olds was evaluated along with their ability to transcode one- to four-digit numbers. As ADAPT predicts, the rate of transcoding errors increased when more production rules were required and when children had low working memory capacity, with these two factors interacting. Moreover, qualitative analysis of the errors produced by high- and low-span children showed that the latter have a developmental delay in the acquisition of the production rules. PMID- 17854822 TI - Comparison of an electrochemiluminescence assay in plate format over a colorimetric ELISA, for the detection of ricin B chain (RCA-B). AB - An electrochemiluminescence (ECL) assay for the detection of the B chain of ricin (RCA-B) in a 96-well plate format was developed in parallel with a colorimetric ELISA utilizing the same pair of antibodies. Sensitivity results were interpreted with the ANOVA and Tukey statistical tests, allowing a direct comparison between the two technologies, that can probably be extended to other protein antigens such as toxins. Reproducibility, repeatability and rapidity of the two techniques were also compared. The ELISA assay utilized an alkaline phosphatase conjugate for signal generation. After optimization, its limit of detection was 400 pg of RCA-B per ml buffer, with an intra-day standard deviation (SD) of 2.2% of the mean and an inter-day SD of 5.1%. The ECL assay utilized ruthenylated antibodies for detection. The ECL measurement was carried out using a Sector PR 400 plate reader. After optimization, its limit of detection was 50 pg of RCA-B per ml buffer, with an intra-day SD of 4.1% of the mean and an inter-day SD of 4.3%. Starting from a pre-coated plate, the ELISA assay was completed in 7 h and the ECL assay took 2.5 h. While reproducibility and repeatability of the two assays were equivalent, this ECL assay in plate format had an 8-fold better sensitivity for RCA-B detection than the colorimetric ELISA in buffer and in various matrices. The ECL assay was also three times faster, and retained the robustness and convenience of the 96-well plate format. PMID- 17854823 TI - Effects of zinc and female aging on nymphal life history in a grasshopper from polluted sites. AB - Insect reproduction is influenced by various factors, including food quality and quantity, temperature, population density and female age. Contamination, including heavy metals, may disturb reproductive processes. The aim of this work was to assess interactions between effects of aging in female Chorthippus brunneus and environmental pollution on their reproduction measured in number of laid eggs. We also compared basic developmental parameters (number of hatchlings, body mass, embryonic developmental rate) in grasshopper nymphs additionally exposed to zinc during diapause. Aging grasshoppers from heavily polluted areas (Olkusz and Szopienice) lay significantly fewer eggs than insects from the reference site (Pilica). Zinc application caused the decrease in hatching success and duration of embryogenesis in insects from each site. This suggests a cumulative effect of female age, pollutants and additional stressing factors. The intensity of this process differed between populations. In insects from the reference site, it was shown in a moderate degree. In insects from Szopienice, an additional stressor exerted a weaker effect than in insects from Pilica. In grasshoppers from Olkusz, we found the strongest decrease of hatching percentage and increase in duration of embryogenesis after zinc intoxication. This may indicate that the population from Olkusz exists at the limit of its energetic abilities. PMID- 17854825 TI - Natural occurrence of Beauveria bassiana in Hypothenemus hampei (Coleoptera: Curculionidae) populations in unsprayed coffee fields. AB - Three unsprayed coffee farms (farm 1, 2 and 3) were studied for the natural occurrence of the insect pathogenic fungus Beauveria bassiana in Hypothenemus hampei populations throughout the rainy season of 2004 (July-November) and 2005 (July-December). B. bassiana infections were found during most sampling dates in both years, on all three farms. The B. bassiana infection levels were higher in 2005 than in 2004 with mean prevalence of 12.1% and 2.7%, respectively. No consistent significant differences in infection level between farms were found in any of the years. B. bassiana infection levels fluctuated widely throughout the season, and peaked at 13.5% on farm 3 in 2004 and at 44.0% on farm 1 in 2005. The H. hampei population was significantly higher in 2004 than in 2005, with 6.9% of the berries infested in 2004 and only 0.7% in 2005. In both years, the H. hampei infestation level was significantly higher on farm 2. No consistent significant differences in H. hampei infestation levels were found between sampling dates on any of the farms. H. hampei infestation levels fluctuated throughout both seasons, and peaked at 15.3% on farm 2 in 2004 and 2.2% on farm 2 in 2005. No consistent density dependent correlation between H. hampei infestation level and B. bassiana infection level was found. Correlations between climatic conditions and B. bassiana or H. hampei were not found. PMID- 17854826 TI - Matrix metalloproteinase-2 degrades the cytoskeletal protein alpha-actinin in peroxynitrite mediated myocardial injury. AB - Matrix metalloproteinase (MMP)-2 mediates myocardial ischemia-reperfusion injury which is characterized by enhanced peroxynitrite biosynthesis during early reperfusion. Direct infusion of peroxynitrite into isolated hearts activates MMP 2 prior to the loss in mechanical function. The mechanical dysfunction is prevented by MMPs inhibitors. MMP-2 is also found in the sarcomere of cardiomyocytes where it cleaves troponin I and myosin light chain I. Cytoskeletal proteins such as alpha-actinin, desmin and spectrin are found in close association with the sarcomere and are known to be degraded in ischemia reperfusion injury. It remains unknown whether these proteins are degraded in peroxynitrite-induced myocardial injury and if cytoskeletal proteins are also targets for MMP-2. Peroxynitrite (80 microM) was infused into isolated rat hearts which led to a delayed onset but rapidly developing decline in mechanical function. The MMPs inhibitor PD-166793 or the peroxynitrite scavenger glutathione prevented the decline in cardiac function. At the end of perfusion, alpha-actinin levels were decreased by 45+/-3% in peroxynitrite-infused hearts as compared to control hearts; however, this was normalized to that of control hearts with either PD-166793 or glutathione. Cardiac desmin and alphaII spectrin levels were unaltered following peroxynitrite infusion. alpha-Actinin and to a lesser extent desmin are susceptible to in vitro proteolysis by MMP-2 whereas spectrin is resistant. Cardiac dysfunction induced by peroxynitrite involves degradation of alpha-actinin that may be mediated by the proteolytic action of MMP-2. PMID- 17854827 TI - Structural and kinetic properties of lumazine synthase isoenzymes in the order Rhizobiales. AB - 6,7-Dimethyl-8-ribityllumazine synthase (lumazine synthase; LS) catalyzes the penultimate step in the biosynthesis of riboflavin in plants and microorganisms. This protein is known to exhibit different quaternary assemblies between species, existing as free pentamers, decamers (dimers of pentamers) and icosahedrally arranged dodecamers of pentamers. A phylogenetic analysis on eubacterial, fungal and plant LSs allowed us to classify them into two categories: Type I LSs (pentameric or icosahedral) and Type II LSs (decameric). The Rhizobiales represent an order of alpha-proteobacteria that includes, among others, the genera Mesorhizobium, Agrobacterium and Brucella. Here, we present structural and kinetic studies on several LSs from Rhizobiales. Interestingly, Mesorhizobium and Brucella encode both a Type-I LS and a Type-II LS called RibH1 and RibH2, respectively. We show that Type II LSs appear to be almost inactive, whereas Type I LSs present a highly variable catalytic activity according to the genus. Additionally, we have solved four RibH1/RibH2 crystallographic structures from the genera Mesorhizobium and Brucella. The relationship between the active-site architecture and catalytic properties in these isoenzymes is discussed, and a model that describes the enzymatic behavior is proposed. Furthermore, sequence alignment studies allowed us to extend our results to the genus Agrobacterium. Our results suggest that the selective pressure controlling the riboflavin pathway favored the evolution of catalysts with low reaction rates, since the excess of flavins in the intracellular pool in Rhizobiales could act as a negative factor when these bacteria are exposed to oxidative or nitrosative stress. PMID- 17854828 TI - A conserved small RNA promotes discoordinate expression of the glmUS operon mRNA to activate GlmS synthesis. AB - Many bacterial genes of related function are organized in operons and transcribed as polycistronic mRNAs to ensure the coordinate expression of the individual cistrons. Post-transcriptional modulation of such mRNAs can alter the expression of downstream cistrons, resulting in discoordinate protein synthesis from an operon mRNA. Several factors, including small non-coding RNAs (sRNAs), have been described that act collectively as repressors within polycistronic mRNAs. We describe the first case of discoordinated operon expression in which a downstream cistron is activated at the post-transcriptional level. We report that GlmY sRNA activates GlmS synthesis from the Escherichia coli glmUS mRNA without altering GlmU expression. The sRNA is shown to be structurally and functionally conserved in diverse enterobacteria; its transcription may be controlled by the alternative sigma factor, sigma(54). Our data suggest that Gram-negative bacteria evolved a mechanism of glmS riboregulation that is distinct from the glmS riboswitch mechanism of Gram-positive bacteria. PMID- 17854829 TI - Phosphorylation-dependent conformational transition of the cardiac specific N extension of troponin I in cardiac troponin. AB - We present here the solution structure for the bisphosphorylated form of the cardiac N-extension of troponin I (cTnI(1-32)), a region for which there are no previous high-resolution data. Using this structure, the X-ray crystal structure of the cardiac troponin core, and uniform density models of the troponin components derived from neutron contrast variation data, we built atomic models for troponin that show the conformational transition in cardiac troponin induced by bisphosphorylation. In the absence of phosphorylation, our NMR data and sequence analyses indicate a less structured cardiac N-extension with a propensity for a helical region surrounding the phosphorylation motif, followed by a helical C-terminal region (residues 25-30). In this conformation, TnI(1-32) interacts with the N-lobe of cardiac troponin C (cTnC) and thus is positioned to modulate myofilament Ca2+-sensitivity. Bisphosphorylation at Ser23/24 extends the C-terminal helix (residues 21-30) which results in weakening interactions with the N-lobe of cTnC and a re-positioning of the acidic amino terminus of cTnI(1 32) for favorable interactions with basic regions, likely the inhibitory region of cTnI. An extended poly(L-proline)II helix between residues 11 and 19 serves as the rigid linker that aids in re-positioning the amino terminus of cTnI(1-32) upon bisphosphorylation at Ser23/24. We propose that it is these electrostatic interactions between the acidic amino terminus of cTnI(1-32) and the basic inhibitory region of troponin I that induces a bending of cTnI at the end that interacts with cTnC. This model provides a molecular mechanism for the observed changes in cross-bridge kinetics upon TnI phosphorylation. PMID- 17854824 TI - Analysis of transcripts and proteins expressed in the salivary glands of Hessian fly (Mayetiola destructor) larvae. AB - Hessian fly (Mayetiola destructor) larvae are thought to manipulate host growth and metabolism through salivary secretions. However, the transcriptome and proteome of Hessian fly salivary glands have not been systematically analyzed. In this research, we analyzed Expressed-Sequence-Tags (EST) representing 6106 cDNA clones randomly selected from four libraries made from dissected salivary glands. We also analyzed the protein composition of dissected salivary glands using one- and two-dimensional gel electrophoresis as well as LC-MS/MS analysis. Transcriptomic analysis revealed that approximately 60% of the total cDNA clones and 40% of assembled clusters encoded secretory proteins (SP). The SP-encoding cDNAs were grouped into superfamilies and families according to sequence similarities. In addition to the high percentage of SP-encoding transcripts, there was also a high percentage of transcripts encoding proteins that were either involved directly in protein synthesis or in house-keeping functions that provide conditions necessary for protein synthesis. Proteomic analysis also revealed a high percentage of proteins involved in protein synthesis either directly or indirectly. The high percentage of SP-encoding transcripts and high percentage of proteins related to protein synthesis suggested that the salivary glands of Hessian fly larvae are indeed specialized tissues for synthesis of proteins for host injection. However, LC-MS/MS analysis of 64 proteins did not identify any SPs corresponding to the cDNA sequences. The lack of accumulation of SPs in the salivary glands indicated the SPs were likely secreted as soon as they were synthesized. PMID- 17854830 TI - Structural studies of the final enzyme in the alpha-aminoadipate pathway saccharopine dehydrogenase from Saccharomyces cerevisiae. AB - The 1.64 A structure of the apoenzyme form of saccharopine dehydrogenase (SDH) from Saccharomyces cerevisiae shows the enzyme to be composed of two domains with similar dinucleotide binding folds with a deep cleft at the interface. The structure reveals homology to alanine dehydrogenase, despite low primary sequence similarity. A model of the ternary complex of SDH, NAD, and saccharopine identifies residues Lys77 and Glu122 as potentially important for substrate binding and/or catalysis, consistent with a proton shuttle mechanism. Furthermore, the model suggests that a conformational change is required for catalysis and that residues Lys99 and Asp281 may be instrumental in mediating this change. Analysis of the crystal structure in the context of other homologous enzymes from pathogenic fungi and human sources sheds light into the suitability of SDH as a target for antimicrobial drug development. PMID- 17854831 TI - Association of platelet-derived soluble glycoprotein VI in plasma with Alzheimer's disease. AB - Accumulating evidence from epidemiological, clinical and experimental studies suggests that vascular risk factors and angiopathic mechanisms are involved in the pathogenesis of Alzheimer's disease (AD). Platelets could be the missing link between AD and the vasculature. Soluble glycoprotein VI (sGPVI) and beta thromboglobulin (beta-TG) plasma and cerebrospinal fluid (CSF) levels as markers of platelet activity were measured in 30 AD patients and 20 age-matched healthy elderly controls by ELISA. The severity of dementia was assessed by mini-mental state examination (MMSE). We found in AD patients significantly decreased sGPVI plasma levels (0.55+/-0.18ng/ml) as compared to healthy controls (0.75+/ 0.43ng/ml; p=0.033). In AD patients, sGPVI levels were positively correlated with beta-TG plasma levels (r=0.244, p=0.05) and with cognitive status as measured by MMSE score (r=0.271; p=0.048). In unconcentrated CSF samples, levels of beta-TG and sGPVI were below the detection limit of the assays in AD patients and healthy controls. Our results suggest an association of sGPVI with the pathogenesis of AD. These findings encourage future research into whether sGPVI plasma levels may reflect or even mediate neuroprotective mechanisms in AD. PMID- 17854832 TI - Spinal and bulbar muscular atrophy: skeletal muscle pathology in male patients and heterozygous females. AB - Spinal and bulbar muscular atrophy (SBMA) is an adult form of X-linked motor neuron disease caused by an expansion of a CAG repeat sequence in the first exon of the androgen receptor (AR) gene. Nuclear accumulation of mutant AR with expanded polyglutamines in motor neurons is a major pathogenic mechanism. To characterize muscle involvement in SBMA the skeletal muscle biopsies of 8 SBMA patients and 3 female carriers were studied. Six of 8 SBMA patients showed myogenic changes together with the neurogenic atrophy in their muscle biopsy. Myopathic abnormalities did not correlate with disease duration and were more prominent in the muscle of patients with an higher degree of disability. In all patients plasma CK levels were more elevated than what usually occurs in denervative diseases. Both neurogenic and myopathic changes were also observed in female carriers. Here we suggest that myopathic changes in SBMA muscle are not only related to denervation and that muscle satellite cells may have a role in the pathogenesis of muscle damage. PMID- 17854833 TI - Preliminary evidences of a NOS2A protective effect from relapsing-remitting multiple sclerosis. AB - The gene encoding the inducible form of Nitric Oxide Synthase (NOS2A) has been considered with interest in the evaluation of the genetic predisposition to Multiple Sclerosis (MS). The aim of the present study was to address the possible contribution of two microsatellites repeats of the NOS2A promoter region - (CCTTT)(n) and (AAAT)(n) - to MS susceptibility. One hundred and thirteen Italian patients with clinically definite RRMS and 237 age and sex matched healthy controls from Calabria (South Italy) were studied. The distribution analysis of the markers frequencies showed that the (CCTTT)(14) allele was found in 11.5% of the RRMS patients and in 25.3% of the healthy subjects, with a statistically significant difference (chi(2)=8.843, p=0.003). This data seems to confer a significant protection against MS (OR=0.348; 95% CI=0.174-0.693, corrected for age and gender). No association with MS susceptibility was observed for the bi allelic (AAAT)(n) microsatellite. In conclusion, we found that the NOS2A (CCTTT)(14) allele was detected more frequently in the control group than in the RRMS patients, thus confirming the scientific interest on this marker. PMID- 17854834 TI - Non-pathogenic protein aggregates in skeletal muscle in MLF1 transgenic mice. AB - Protein aggregate formation in muscle is thought to be pathogenic and associated with clinical weakness. Over-expression of either wild type or a mutant form of myeloid leukemia factor 1 (MLF1) in transgenic mouse skeletal muscle and in cultured cells resulted in aggregate formation. Aggregates were detected in MLF1 transgenic mice at 6 weeks of age, and increased in size with age. However, histological examination of skeletal muscles of MLF1 transgenic mice revealed no pathological changes other than the aggregates, and RotaRod testing did not detect functional deficits. MLF1 has recently been identified as a protein that could neutralize the toxicity of intracellular protein aggregates in a Drosophila model of Huntington's disease (HD). We also demonstrate that MLF1 interacts with MRJ, a heat shock protein, which can independently neutralize the toxicity of intracellular protein aggregates in the Drosophila HD model. Our data suggest that over-expression of MLF1 has no significant impact on skeletal muscle function in mice; that progressive formation of protein aggregates in muscle are not necessarily pathogenic; and that MLF1 and MRJ may function together to ameliorate the toxic effects of polyglutamine or mutant proteins in myodegenerative diseases such as inclusion body myositis and oculopharyngeal muscular dystrophy, as well as neurodegenerative disease. PMID- 17854835 TI - Prior antiplatelet use and infarct volume in ischemic stroke. AB - BACKGROUND: Conflicting data exist on the role of antiplatelet agents in reducing incident ischemic stroke magnitude, but most prior studies used clinically assessed neurologic deficit as the index of stroke extent rather than more precise volumetric measurements of infarct size. We assessed the relation of premorbid antiplatelet use to initial diffusion-weighted MRI (DWI) lesion volumes among acute ischemic stroke patients. METHODS: Consecutive patients presenting within 24 h of ischemic stroke over an 18-month period were studied. DWI lesions were outlined using a semi-automated threshold technique. Subjects were categorized into two groups: antiplatelet (AP) or no antithrombotic (NA). The relationship between prestroke antithrombotic status and DWI infarct volumes was examined using multivariate quantile regression. RESULTS: One hundred sixty-six individuals met study criteria: 75 AP and 91 NA patients. Median DWI volume was lower in the AP group than in the NA group (1.5 cc vs. 5.4 cc, p=0.031). A multivariable model (adjusting for age, history of transient ischemic attack, admission temperature, admission blood pressure, admission serum glucose, stroke onset to imaging interval, stroke mechanism, premorbid statin and antihypertensive use) demonstrated smaller infarcts in the AP vs. NA group (adjusted volume difference: -1.3 cc, 95% CI=-0.09, -2.5, p=0.037). Prior statin use, no history of TIA, large vessel atherosclerosis and microvascular ischemic disease stroke mechanism were also independently associated with reduced infarct volume. CONCLUSIONS: Prior antiplatelet treatment is independently associated with reduced cerebral infarct volume among acute ischemic stroke patients. Premorbid statin use, TIA history and stroke mechanism also predict infarct volume in ischemic stroke. PMID- 17854836 TI - Variability in the clinical expression of Parkinson's disease. AB - Parkinsonism is a clinical syndrome characterized by bradykinesia, hypo /akinesia, muscular rigidity, and resting tremor, mainly caused by Parkinson's disease (PD). Symptoms of PD are due to a progressive loss of nigral neurons causing striatal dopaminergic denervation. However, nigral degeneration is only a part of the underlying synucleinopathy, and clinical symptoms go far beyond motor parkinsonism. Olfactory disturbances, fatigue, pain, autonomic dysfunction, sleep fragmentation, depression, and dementia with or without psychosis are frequently seen. The variability in the expression of these signs and symptoms, as discussed in this paper, might be explained by the specific topographical sequence of the pathology, depending on the extent and progression of the degenerative process at defined sites. Better insight in the clinicopathological correlations of this disease may help to further develop early diagnosis and adequate therapeutic strategies. PMID- 17854837 TI - A fitness based analysis of Daisyworld. AB - The Gaia hypothesis [Lovelock, J., Margulis, L., 1974. Atmospheric homeostasis: the Gaia hypothesis. Tellus 26, 1], that the earth functions as a self-regulating system, has never sat particularly comfortably with ideas in mainstream biology [Anon, 2002. In pursuit of arrogant simplicities. Nature 416, 247]. A lack of any clear role for evolution in the model has led to claims of teleology-that self regulation emerges because it is pre-ordained to do so [Doolittle, W.F., 1981. Is nature really motherly? CoEvol. Q. 58-63; Dawkins, R., 1979. The Extended Phenotype. Oxford University Press, Oxford]. The Daisyworld parable [Watson, A.J., Lovelock, J.E., 1983. Biological homeostasis of the global environment--the parable of Daisyworld. Tellus B 35, 284], a simple mathematical illustration of Gaia, went some way to addressing these critiques but, despite recent success in incorporating natural selection [Stocker, S.,1995. Regarding mutations in Daisyworld models. J. Theor. Biol. 175, 495; Lenton, T.M., 1998. Gaia and natural selection. Nature 394, 439; Lenton, T.M., Lovelock, J.E., 2001. Daisyworld revisited: quantifying biological effects on planetary self-regulation. Tellus B 53, 288; Wood, A.J., Ackland, G.J., Lenton, T.M., 2006. Mutation of albedo and growth response leads to oscillations in a spatial Daisyworld. J. Theor. Biol. 242, 188], it remains a widely held view that the ideas are inconsistent with biological principles. We show that standard methodology from quantitative genetics can be used to predict the stationary states and dynamic behaviour of Daisyworlds. The system regulates its temperature due to the low-level evolutionary dynamics of competition between the thermally coupled daisies, no higher level principle is invoked. A reconciliation of Gaia with evolutionary theory may allow further development of evolutionary arguments for the existence of global self-regulatory systems. PMID- 17854838 TI - Orientational relaxation time of bottom-heavy squirmers in a semi-dilute suspension. AB - One of the important quantities to characterize unsteady behaviour of a cell suspension is the orientational relaxation time, which is the time scale for a micro-organism to re-orientate to its preferred direction from disorientated conditions. In this paper, a swimming micro-organism is modelled as a squirming sphere with prescribed tangential surface velocity, in which the centre of mass of the sphere is displaced from the geometric centre (bottom-heaviness). The orientational relaxation time of bottom-heavy squirmers in a suspension is investigated both analytically and numerically. The three-dimensional movement of 64 identical squirmers in a fluid otherwise at rest, contained in a cube with periodic boundary conditions, is dynamically computed, for random initial positions and orientations. The effects of volume fraction of squirmers, the bottom-heaviness and the squirming mode on the relaxation time are discussed. The results for a semi-dilute suspension show that both the mean stresslet strength and the orientational relaxation time decrease from those for a dilute suspension. We also observe a stress overshoot in some cases. The mechanism for this is different from that for a visco-elastic fluid, and is explained by the change with time of the orientation of squirmers. PMID- 17854839 TI - Selfish punishment: altruism can be maintained by competition among cheaters. AB - Altruistic punishment refers to a class of behaviors that deters cheating at a cost to the punisher, making it a form of second-order altruism. Usually, it is assumed that the punishers are themselves "solid citizens" who refrain from cheating. We show in a simulation model that altruism and punishment paradoxically become negatively correlated, leading to a form of selfish punishment. Examples of selfish punishment can be found in organisms as diverse as wasps, birds, and humans. PMID- 17854840 TI - Delayed cytoprotection induced by hypoxic preconditioning in cultured neonatal rat cardiomyocytes: role of GRP78. AB - Hypoxic preconditioning (HPC) has been well demonstrated to have potent protective effects in many cell types; however, the mechanisms responsible for this phenomenon are not fully understood. Recently, glucose-regulated protein 78 (GRP78), an inducible molecular chaperon, was indicated to be associated with ischemic preconditioning. We hypothesized that HPC protects cardiomyocytes against hypoxia by inducing GRP78 in cultured neonatal rat cardiomyocytes. HPC was induced by exposing cardiomyocytes to brief hypoxia (1% O(2), 30 min) followed by reoxygenation. GRP78 was expressed constitutively in cultured cardiomyocytes and its expression was enhanced at 12 h, peaked at 24 h (207.3+/ 23.6% of the baseline), and was sustained for up to 72 h after HPC. Twenty-four hours after HPC, the myocytes were subjected to prolonged hypoxia (1% O(2), 12 h). The lactic dehydrogenase (LDH) release and malondialdehyde (MDA) content were reduced, while cell viability and superoxide dismutase (SOD) activity were increased in the preconditioned cells compared with the non-HPC cells. The GRP78 protein level was higher in cells exposed to both HPC and hypoxia than in the cells exposed to HPC alone or hypoxia alone. Heat shock protein 70 (HSP70) was induced in parallel by late HPC. Transfection of GRP78 antisense oligonucleotides blocked GRP78 expression but not HSP70, resulting in attenuated cardioprotection afforded by late HPC. Furthermore, inducing GRP78 by gene transfer protected cardiomyocytes from hypoxic injury. These findings demonstrate that the induction of GRP78 partially mediates the late HPC, suggesting that GRP78 is a novel mechanism responsible for the late cytoprotection of HPC. PMID- 17854841 TI - Biodegradative potential and characterization of psychrotolerant polychlorinated biphenyl-degrading marine bacteria isolated from a coastal station in the Terra Nova Bay (Ross Sea, Antarctica). AB - Antarctic marine bacteria were screened for their ability to degrade polychlorinated biphenyls (PCB) as the sole carbon and energy source at both 4 degrees C and 15 degrees C. PCB-degrading isolates (7.1%) were identified by sequencing their 16S rDNA as Pseudoalteromonas, Psychrobacter and Arthrobacter members. One representative isolate per genera was selected for evaluating the biodegradative potential under laboratory scale and phenotypically characterized. Removal of individual PCB congeners was between 35.6% and 79.8% at 4 degrees C and between 0.4% and 82.8% at 15 degrees C. Differences in the removal patterns of PCB congeners were observed in relation to the phylogenetic affiliation: Arthrobacter isolate showed similar biodegradation efficiencies when growing at 4 degrees C and 15 degrees C, while Pseudoalteromonas better degraded PCBs at 15 degrees C. No biodegradation was detected for Psychrobacter isolate at 4 degrees C. Results obtained highlight the occurrence of PCB-degrading bacteria in Antarctic seawater and suggest the potential exploitation of autochthonous bacteria for PCB bioremediation in cold marine environments. PMID- 17854842 TI - Bioaccumulation and enantiomeric profiling of organochlorine pesticides and persistent organic pollutants in the killer whale (Orcinus orca) from British and Irish waters. AB - Concentrations and enantiomeric profiles for a range of organochlorine compounds are reported in blubber samples from a number of individual killer whales (Orcinus orca) from British and Irish waters. Elevated contaminant levels and enriched isotopic ratios were determined in one individual whale sampled in the Scottish Western Isles compared to the others suggesting marine mammal based dietary influences. The potential application of isotopic ratios to model contaminant uptake, enantioselective enrichment and accumulation is demonstrated. Data are presented which provide information on enantioselective enrichment factors (EFs) for o,p'-DDT, alpha-HCH and toxaphene congeners CHB26 and CHB 50. This dataset further improves the current database on reported levels of a number of contaminants and provides additional background information on potential metabolic processes in killer whales from British and Irish waters. PMID- 17854843 TI - The adaptive dynamics of the evolution of host resistance to indirectly transmitted microparasites. AB - We use adaptive dynamics and pairwise invadability plots to examine the evolutionary dynamics of host resistance to microparasitic infection transmitted indirectly via free stages. We investigate trade-offs between pathogen transmission rate and intrinsic growth rate. Adaptive dynamics distinguishes various evolutionary outcomes associated with repellors, attractors or branching points. We find criteria corresponding to these and demonstrate that a major factor deciding the evolutionary outcome is whether trade-offs are acceleratingly or deceleratingly costly. We compare and contrast two models and show how the differences between them lead to different evolutionary outcomes. PMID- 17854844 TI - The effects of ladasten on dopaminergic neurotransmission and hippocampal synaptic plasticity in rats. AB - Derivatives of adamantane, like memantine, are potentially neuroprotective drugs for the favourable care of Alzheimer's and Parkinson's diseases. A further adamantane derivate is N-(2-adamantyl)-N-(para-bromophenyl)-amine (ladasten) which is capable to modulate animal performance in different learning paradigms. To clarify if some of those behavioural alterations are mediated by modulation of catecholamine syntheses we studied the effects of single administration of ladasten (50 mg/kg, per os) on catecholamines' biosynthesis in the ventral tegmental area, nucleus accumbens, hypothalamus, striatum and hippocampus. We found that ladasten differentially regulates tyrosine hydroxylase mRNA and protein as well as dopamine and L-DOPA content. We then investigated the effects of ladasten on activity-dependent hippocampal synaptic plasticity in vitro and found that application of 10 microM ladasten transforms short-term potentiation of synaptic transmission to a long-lasting form. A transformation of short-term into long-term potentiation was also observed, when ladasten was applied 40 min after a single 100 Hz 200 ms tetanization. This reinforcement was blocked by the protein synthesis inhibitor anisomycin and could be attenuated by the D1/D5 receptor antagonist SCH23390. These results suggest that ladasten induces reinforcement of short-term potentiation via protein synthesis and dopamine dependent mechanisms. PMID- 17854845 TI - Impulsivity and risk-taking behavior in focal frontal lobe lesions. AB - Frontal lobe dysfunction may underlie excessively impulsive and risky behavior observed in a range of neurological disorders. We devised a gambling task to examine these behavior tendencies in a sample of patients who had sustained focal damage to the frontal lobes or nonfrontal cortical regions as well as in a matched sample of healthy control subjects. The main objectives of the study were: (1) to behaviorally dissociate impulsivity and risk-taking; (2) to examine potential associations between specific frontal lesion sites and impulsivity or risk-taking; (3) to investigate the influence of reinforcement and trial timing on both behaviors. Our results indicated that patients and controls were equally likely to perform impulsively. Risk-taking performance strategies, however, were related to left ventrolateral and orbital lesion sites. Moreover, risk-taking was also associated with blunted response alteration following a nonrewarded trial. Patients and control subjects showed identical responses to reward-timing manipulations consistent with formal decision-making theory. These findings suggest that ventrolateral and orbital lesions are related to the reward-based aspects of decision-making (risk-taking) rather than to simple response disinhibition (impulsivity). Reduced reaction to the negative consequences of one's actions may underlie this behavior pattern. PMID- 17854846 TI - The role of the striatum in sentence processing: evidence from a priming study in early stages of Huntington's disease. AB - The role of sub-cortical structures such as the striatum in language remains a controversial issue. Based on linguistic claims that language processing implies both recovery of lexical information and application of combinatorial rules it has been shown that striatal damaged patients have difficulties applying conjugation rules while lexical recovery of irregular forms is broadly spared (e.g., Ullman, M. T., Corkin, S., Coppola, M., Hickok, G., Growdon, J. H., Koroshetz, W. J., et al. (1997). A neural dissociation within language: Evidence that the mental dictionary is part of declarative memory, and that grammatical rules are processed by the procedural system. Journal of Cognitive Neuroscience, 9(2), 266-276). Here we bolstered the striatum-rule hypothesis by investigating lexical abilities and rule application at the phrasal level. Both processing aspects were assessed in a model of striatal dysfunction, namely Huntington's disease (HD). Using a semantic priming task we compared idiomatic prime sentences involving lexical access to whole phrases (e.g., "Paul has kicked the bucket") with idiom-derived sentences that contained passivation changes involving syntactic movement rules (e.g., "Paul was kicked by the bucket"), word changes (e.g., "Paul has crushed the bucket") or either. Target words that were either idiom-related (e.g., "death") reflecting lexical access to idiom meanings, word related (e.g., "bail") reflecting lexical access to single words, or unrelated (e.g., "table"). HD patients displayed selective abnormalities with passivated sentences whereas priming was normal with idioms and sentences containing only word changes. We argue that the role of the striatum in sentence processing specifically pertains to the application of syntactic movement rules whereas it is not involved in canonical rules required for active structures or in lexical processing aspects. Our findings support the striatum-rule hypothesis but suggest that it should be refined by tracking the particular kind of language rules depending on striatal computations. PMID- 17854847 TI - Motivational effects of intraorally-infused ethanol in rat pups in an operant self-administration task. AB - Motivational effects of self-administered ethanol have rarely been studied in preweanling rats due primarily to the lack of age-appropriate operant tasks. The present experiments assessed the hedonic effects of intraoral ethanol in infant rats self-administered by activating a touch sensor. On postnatal day (PD) 13 pups were pre-exposed to the drug's pharmacological and/or sensory effects. Operant sessions were conducted during PDs 14-16 (Experiments 1 and 2). Paired animals were placed in chambers equipped with a touch-sensitive disk and received an intraoral infusion of ethanol (3 or 5% v/v, 5 microl) after each sensor contact. Yoked controls were equated for number and distribution of ethanol infusions but had no control over the contingency between operant behavior and intraoral infusion. In Experiment 2, training trials were preceded by a non reinforced phase. Paired pups performed fewer operant responses than controls and decreased their operant responses across sessions. These results suggest that intraoral self-administered ethanol has an aversive hedonic value in two-week old rats. Operant behavior seems to have been associated with aversive orosensory effects derived from intraoral ethanol infusion. PMID- 17854849 TI - Diterpenoids from the pericarp of Platycladus orientalis. AB - Eight labdane-type diterpenes, 7beta,13S-dihydroxylabda-8(17),14-dien-19-oic acid (1), 12R,15-dihydroxylabda-8(17),13E-dien-19-oic acid (3c), 12R,15-dihydroxylabda 8(17),13Z-dien-19-oic acid (3d), 12R,13R,14S-trihydroxylabda-12,15-epoxy-8(17)-en 19-oic acid (4a), 12S,13S,14R-trihydroxylabda-12,15-epoxy-8(17)-en-19-oic acid (4b), 15-hydroxy-12-oxolabda-8(17),13E-dien-19-oic acid (5), 14R,15 dihydroxylabda-8(17),12Z-dien-19-oic acid (7a) and 14S,15-dihydroxylabda 8(17),12Z-dien-19-oic acid (7b), along with 20 known diterpenoids, were isolated from the pericarp of Platycladus orientalis. Their structures were unambiguously elucidated by NMR spectroscopic and single crystal X-ray diffraction analyses, as well as via chemical correlation conversion. NMR spectroscopic data of known isomers 8c and 8d were reported as a supplement to existing data. PMID- 17854848 TI - Suppression of reactive oxygen species by glyceraldehyde-3-phosphate dehydrogenase. AB - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a classical glycolytic enzyme, is involved in cellular energy production and has important housekeeping functions. In this report, we show that a GAPDH from Arabidopsis, GAPDHa, has a novel function involved in H(2)O(2)-mediated cell death in yeast and Arabidopsis protoplasts. GAPDHa was cloned along with other plant genes that suppress Bax induced cell death in yeast. Flow cytometry analyses with dihydrorhodamine 123 indicated that H(2)O(2) production mediated by Bax expression in yeast cells was greatly reduced when Bax was coexpressed with GAPDHa. In plants, GAPDHa transcript levels were greatly increased by H(2)O(2) treatment. Furthermore, transformation of GAPDHa into Arabidopsis protoplasts strongly suppressed heat shock-induced H(2)O(2) production and cell death. Together, our results indicate that GAPDH controls generation of H(2)O(2) by Bax and heat shock, which in turn suppresses cell death in yeast and plant cells. PMID- 17854850 TI - Diterpene constituents of leaves from Juniperus brevifolia. AB - The dichloromethane extract from leaves of Juniperus brevifolia, through chromatographic fractionations yield six compounds: 3beta-hydroxy-abieta-8,11,13 trien-7-one, 18-hydroxy-sandaracopimara-8(14),15-dien-7-one, sandaracopimara 8(14),15-dien-18-yl formate; and the first examples of sandaracopimaranes and abieta-8,11,13-triene diterpenoids with a large aliphatic chain on C-18, abieta 8,11,13-trien-18-yl hexadecanoate, 7-oxoabieta-8,11,13-trien-18-yl hexadecanoate, sandaracopimara-8(14),15-dien-18-yl hexadecanoate. Moreover fifteen known compounds were also isolated, some of them for the first time identified on Juniperus genus. The compound abieta-8,11,13-trien-18-yl formate is reported for the first time as a natural product. All the structures were established by spectroscopic methods. 2D NMR techniques have allowed the revision of certain previously reported (13)C NMR assignments. Studies on the isolated new compounds showed those possessing a diterpenol ester of a long-chain fatty acid present lipophilicity very distinct from other diterpenoid compounds. PMID- 17854851 TI - Polar secondary metabolites of Ferula persica roots. AB - Phytochemical investigation of the methanolic extract of the dried roots of Ferula persica resulted in four sesquiterpene coumarin glycosides, persicaosides A-D, and two known phytosterol glucosides, sitosterol 3-O-beta-glucoside and stigmasterol 3-O-beta-glucoside. The structures of these compounds were elucidated by extensive spectroscopic methods including 1D-((1)H and (13)C) and 2D NMR experiments (DQF-COSY, HSQC, HMBC, and ROESY) as well as ESIMS and TOFMS analyses. PMID- 17854852 TI - 5alpha-Androstane-3beta,17beta-diol (3beta-diol), an estrogenic metabolite of 5alpha-dihydrotestosterone, is a potent modulator of estrogen receptor ERbeta expression in the ventral prostrate of adult rats. AB - Prostate is one of the major targets for dihydrotestosterone (DHT), however this gland is also recognized as a nonclassical target for estrogen as it expresses both types of estrogen receptors (ER), especially ERbeta. Nevertheless, the concentrations of aromatase and estradiol in the prostate are low, indicating that estradiol may not be the only estrogenic molecule to play a role in the prostate. It is known that DHT can be metabolized to 5alpha-androstane 3beta,17beta-diol (3beta-diol), a hormone that binds to ERbeta but not to AR. The concentration of 3beta-diol in prostate is much higher than that of estradiol. Based on the high concentration of 3beta-diol and since this metabolite is a physiological ERbeta ligand, we hypothesized that 3beta-diol would be involved in the regulation of ERbeta expression. To test this hypothesis, adult male rats were submitted to castration followed by estradiol, DHT or 3beta-diol replacement. ERbeta and AR protein levels in the prostate were investigated by immunohistochemistry and Western blotting assays. The results showed that after castration, the structure of the prostate was dramatically changed and ERbeta and AR protein levels were decreased. Estradiol had just minor effects on the parameters analyzed. DHT-induced partial recovery of ERbeta while it was the most effective inductor of AR expression. Replacement with 3beta-diol-induced the highest levels of ERbeta, but was comparatively less effective in recovering the AR expression and the gland structure. These results offer evidence that one functional role of 3beta-diol in the prostate may be autoregulation of its natural receptor, ERbeta. PMID- 17854853 TI - Purification, characterization and potent lung lesion activity of an L-amino acid oxidase from Agkistrodon blomhoffii ussurensis snake venom. AB - L-amino acid oxidases (LAOs) are one of the major components of snake venoms, which possess numerous biological functions. However, little is known of the influence of LAOs on organ lesions. In the present study, a unique LAO from Agkistrodon blomhoffii ussurensis snake venom named ABU-LAO was purified by Heparin-Sepharose FF chromatography followed by an ion-exchange chromatography procedure. The purified ABU-LAO appears a dimer with a molecular mass of approximately 108.8kDa. Kinetics studies showed that ABU-LAO is very active towards its substrates L-Asn, L-Phe, L-Tyr, L-Leu, L-Ile and L-Trp. The most striking observation in the present study is that ABU-LAO causes severe pneumorrhagia, pulmonary interstitial edema, fusion of pulmonary alveoli, cardiac interstitial edema and bleeding when being intravenously injected into BALB/c mice. ABU-LAO also induces liver cell necrosis and release of cytokines including IL-6, IL-12 and IL-2 from highly purified human peripheral blood monocytes and T cells, respectively. In conclusion, ABU-LAO potently induces lesions in lungs and livers. The ability of ABU-LAO will contribute to the understanding of the pathogenesis of snakebite wound. PMID- 17854854 TI - Effect of RGD-disintegrins on melanoma cell growth and metastasis: involvement of the actin cytoskeleton, FAK and c-Fos. AB - The effects and molecular mechanisms of RGD-disintegrins isolated from snake venoms on the growth and metastatic potential of B16F10-melanoma cells were investigated. Jarastatin (JT) from Bothrops jararaca is a ligand of alpha(5)beta(1), alpha(v)beta(3) and alpha(m)beta(2) integrins, flavoridin (FL) from Trimeresurus flavoridis binds preferentially to alpha(5)beta(1) and kistrin (KR) from Calloselasma rhodostoma is a selective ligand of alpha(v)beta(3). When injected simultaneously with melanoma cells in mice, the three disintegrins significantly reduced tumor lung colonization. On the other hand, JT and FL, but not KR, inhibited B16F10 cell growth in vitro. Interaction of JT or FL with melanoma cells induced actin cytoskeleton rearrangement, increasing actin polymerization and FAK phosphorylation. The effect of FL correlates with the decrease in the constitutively high nuclear content of c-Fos, whereas JT interfered with NF-kappaB translocation in melanoma cells. None of the disintegrins produced alterations in the nuclear Erk-2. The results provide further evidence to suggest RGD-disintegrins as potent anti-metastatic agents in vivo, and indicate that their interaction with alpha(5)beta(1) integrin interfere with integrin-couple signaling, down-regulating transcription factors and negatively modulating cell proliferation. These effects may contribute to inhibition of melanoma cell invasion in vivo. PMID- 17854855 TI - An epidemiological and a clinical study on scorpionism by the Iranian scorpion Hemiscorpius lepturus. AB - The aim of this retrospective descriptive study was to describe the epidemiological and some common clinical symptoms and signs among humans stung by Hemiscorpius lepturus (H. lepturus) in the southwest province of Iran, Khuzestan. Cases were collected from hospital patients' files referred to two major Khuzestan hospitals over 5 years. Only definite stings of this species, identified by trained health-caring personnel, were included in this study. Epidemiological and clinical signs and symptoms were recorded. There were 354 scorpion victims, 43% of whom were from rural areas. Stings mainly occurred at night between 7p.m. and 5a.m. (56.1%), or from early morning 5a.m. to 12a.m. (38.6%), 41% of which occurred in the lower extremities. Eighty three percent of accidents occurred in mild/hot months of this area between April and October. The age most inflicted was between 1 month to 10 years and 11-20 years old, observed in 39.6% and 26.8% of victims, respectively. Among all the 26,397 scorpion stung files studied over the period of the study, while only 10-15% of stung cases occurred due to this not highly prevalent scorpion of Iran, it was responsible for 89% of the deaths and 92% of hospitalized scorpion-stung patients. The majority of cases were children aged less than 12 years old. Clinical signs and symptoms were both local and systemic. The local symptoms ranged from erythema to severe necrosis with no immediate sensation of pain. Renal toxicity is one of the serious systemic effects, which, if not treated early by administration of the polyvalent antivenom, can progress to severe renal and cardio-respiratory failure. Overall, the findings demonstrate that the characteristic clinical features of envenomation produced by this scorpion differ significantly from those reported for other scorpions in the world. PMID- 17854856 TI - Role of blue green algae biofertilizer in ameliorating the nitrogen demand and fly-ash stress to the growth and yield of rice (Oryza sativa L.) plants. AB - Rice is a major food crop throughout the world; however, accumulation of toxic metals and metalloids in grains in contaminated environments is a matter of growing concern. Field experiments were conducted to analyze the growth performance, elemental composition (Fe, Si, Zn, Mn, Cu, Ni, Cd and As) and yield of the rice plants (Oryza sativa L. cv. Saryu-52) grown under different doses of fly-ash (FA; applied @ 10 and 100 tha(-1) denoted as FA(10) and FA(100), respectively) mixed with garden soil (GS) in combination with nitrogen fertilizer (NF; applied @ 90 and 120 kg ha(-1) denoted as NF(90) and NF(120), respectively) and blue green algae biofertilizer (BGA; applied @ 12.5 kg ha(-1) denoted as BGA(12.5)). Significant enhancement of growth was observed in the plants growing on amended soils as compared to GS and best response was obtained in amendment of FA(10)+NF(90)+BGA(12.5). Accumulation of Si, Fe, Zn and Mn was higher than Cu, Cd, Ni and As. Arsenic accumulation was detected only in FA(100) and its amendments. Inoculation of BGA(12.5) caused slight reduction in Cd, Ni and As content of plants as compared to NF(120) amendment. The high levels of stress inducible non-protein thiols (NP-SH) and cysteine in FA(100) were decreased by application of NF and BGA indicating stress amelioration. Study suggests integrated use of FA, BGA and NF for improved growth, yield and mineral composition of the rice plants besides reducing the high demand of nitrogen fertilizers. PMID- 17854857 TI - Preparation of acidic and alkaline macrocapsules for pH control. AB - A series of experiments was performed to prepare acidic macroencapsulated buffers composed of 20% Ca(H2PO4)(2) and 80% Eudragit S 100 polymer and alkaline macrocapsules composed of 65% K2HPO4 and 35% Eudragit E PO polymer (the powdered form of Eudragit E 100). Eudragit S 100 was shown to be soluble at a pH greater than 7.0, while Eudragit E 100 was soluble at a pH less than 7.0. Both polymers did not impart significant biochemical oxygen demand. The Eudragit E PO polymer solution showed low toxicity (EC50=91%) based on the Microtox Acute Toxicity Test compared to the 0.1mM background phosphate buffer solution (EC50=100%) while the Eudragit S 100 polymer solution showed higher toxicity (EC50=53%). Batch tests showed that the acidic macrocapsules reduced the pH of a 0.1mM phosphate solution from 11 to neutral, while the alkaline macrocapsules increased the pH of a 0.1mM phosphate solution from 3 to neutral. The macrocapsules could potentially be used as an in situ proportional pH controller for groundwater remediation. PMID- 17854858 TI - Perfluorinated acids as novel chemical tracers of global circulation of ocean waters. AB - Perfluorinated acids (PFAs) such as perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) are global environmental contaminants. The physicochemical properties of PFAs are unique in that they have high water solubilities despite the low reactivity of carbon-fluorine bond, which also imparts high stability in the environment. Because of the high water solubilities, the open-ocean water column is suggested to be the final sink for PFOS and PFOA. However, little is known on the distribution of PFAs in the oceans around the world. Here we describe the horizontal (spatial) and vertical distribution of PFAs in ocean waters worldwide. PFOS and PFOA concentrations in the North Atlantic Ocean ranged from 8.6 to 36pg l(-1) and from 52 to 338pg l( 1), respectively, whereas the corresponding concentrations in the Mid Atlantic Ocean were 13-73pg l(-1) and 67-439pg l(-1). These were completely different from the surface waters of the South Pacific Ocean and the Indian Ocean (overall range of <5-11pg l(-1) for PFOS and PFOA). Vertical profiles of PFAs in the marine water column were associated with the global ocean circulation theory. Vertical profiles of PFAs in water columns from the Labrador Sea reflected the influx of the North Atlantic Current in surface waters, the Labrador Current in subsurface waters, and the Denmark Strait Overflow Water in deep layers below 2000m. Striking differences in the vertical and spatial distribution of PFAs, depending on the oceans, suggest that these persistent acids can serve as useful chemical tracers to allow us to study oceanic transportation by major water currents. The results provide evidence that PFA concentrations and profiles in the oceans adhere to a pattern consistent with the global "Broecker's Conveyor Belt" theory of open ocean water circulation. PMID- 17854859 TI - Down-regulation of aquaporin-1 in intrahepatic cholangiocarcinoma is related to tumor progression and mucin expression. AB - Aquaporin-1 (AQP-1) has been found to be important in bile formation across cell membranes of the biliary epithelium, and thus it has been suggested that AQP-1 is involved in the pathogenesis of hepatobiliary disease. To clarify the role of AQP 1 in the development of intrahepatic cholangiocarcinoma, we determined AQP-1 expression in the normal bile duct, 21 cases of biliary dysplasia, and in 112 cases of intrahepatic cholangiocarcinoma by immunohistochemical analysis. Mucus core protein 5AC expression, a poor prognostic marker of intrahepatic cholangiocarcinoma, was also assessed in intrahepatic cholangiocarcinoma cases. High (>50%) expression of AQP-1 was detected in 16% (9/58) of the normal large bile ducts examined, and in 48% (10/21) of the biliary dysplasia samples originating from large bile ducts. High (>50%), low (40 mm) and poorly differentiated histology were significantly more prevalent in the negative AQP-1 group than in the high AQP-1 group. Low or negative AQP-1 expression was associated with positive lymph node metastasis (P=.0001). AQP-1 expression was found to inversely correlate with that of mucus core protein 5AC, and their distributions tended to be complementary. The low and negative AQP-1 expression was an independent prognostic factor by multivariate survival analysis. We concluded that AQP-1 is up-regulated in biliary dysplasia, as compared with in the normal large bile duct, and down-regulation of AQP-1 is associated with mucin production and aggressive progression of intrahepatic cholangiocarcinoma. PMID- 17854860 TI - A non-lethal chemically based approach to investigate the quality of harbour sediments. AB - A non-lethal chemically based approach was used to investigate the quality of harbour sediments receiving combined road runoff and sewage effluents. A previous investigation of the behaviour of the amphipod Corophium volutator linked polycyclic aromatic hydrocarbons (PAH) in sediments corresponding to the probable effects levels listed in the sediment quality guidelines of the Canadian Council of the Marine Environment to a sediment avoidance response. Since the amphipods did not biotransform contaminants, bioaccumulation was the only fate pursued to examine the bioavailability of PAH. For five Halifax Harbour sediments, a relationship was established between the threshold effects level representing the amphipods' avoidance response and the bioaccumulation of PAH. A body burden of 0.3-1.1 mumol/kg (wet weight) was determined for the sum of abundant parental PAH in amphipods exposed to sediments that initiated the behavioural effect. PAH were much more available from spiked sediments than from field sediments, with biota sediment accumulation factors of 2.2-7.8 compared to <0.01-0.3, respectively. Animals exposed to PAH-spiked sediments avoided contaminated sediments when their body burden was up to seven times higher than observed with field sediments. This latter result and two exposures to sediments collected further away from sewage discharges point to a role for unidentified chemicals in the body burden and behaviour relationship. Further research is warranted to develop this promising assessment tool. PMID- 17854861 TI - Contribution for tier 1 of the ecological risk assessment of Cunha Baixa uranium mine (Central Portugal): II. soil ecotoxicological screening. AB - This study presents the first ecotoxicological data concerning the soils of the area surrounding the Cunha Baixa uranium mine. Our main goal was to categorise soils from the area based on their toxicity profiles using a battery of cost- and time-effective bioassays (elutriate approach - Microtox and Daphnia acute tests; whole-soil approach - Microtox and avoidance assays with Eisenia andrei), as a part of tier 1 of an ongoing Environmental Risk Assessment. No acute toxicity was found for any of the 10 sites/soils using Microtox or Daphnia. On the contrary, the behavioural response of E. andrei was found to be an extremely sensitive endpoint, allowing the discrimination of highly to moderately toxic soils based on their toxicity profiles (as a function of soil concentration). Soils exhibiting highest toxicity corresponded to areas subjected to runoffs or sludge deposition from the aquatic effluent, while non-toxic soils were farthest to the mine. Data obtained in avoidance assays strengthen the previous evaluation of risks based on chemical data and supported decisions about proceeding for tier 2. PMID- 17854862 TI - Lead content of dried films of domestic paints currently sold in Nigeria. AB - Children are at higher risk from lead exposure because their developing neural system is susceptible to its neurotoxic effects. We studied lead levels of paints manufactured in Nigeria in 2006. Lead levels in 5 colors of paints, each from different manufacturers were measured using flame-atomic absorption spectroscopy. We found that 96% of the paints had higher than recommended levels of lead. The mean lead level of paints ranged from 84.8 to 50,000 ppm, with mean of 14,500 ppm and median of 15,800 ppm. The main determinant of lead levels was color of the paint. As lead levels in paint sold in the past years in Nigeria are likely to be at least as high as that currently sold, it is likely that many existing houses contain dangerously high levels of lead. Efforts need to be undertaken to assess the presence of high lead levels in existing housing and if detected, intervention programs for eliminating risk of exposure should be developed in addition to measures to increase awareness and enforce regulations leading to the elimination of lead based domestic paint. PMID- 17854863 TI - Trace metal concentrations are higher in cartilage than in bones of scaup and pochard wintering in Poland. AB - Bones and cartilage of two species of diving ducks: the scaup Aythya marila (n=24) and the pochard A. ferina (n=24) were studied. Scaup is protected in Poland where it spends only the winter, while pochard is a game bird, abundant and breeding in Poland. In winter, the two species form large flocks off the southern coast of the Baltic, particularly in the Szczecin Lagoon where they were collected for this study. The bones and cartilage (trachea) were assayed for concentrations (dry weight-based) of three essential metals: iron (Fe), copper (Cu), and zinc (Zn); concentrations of the two toxic metals: lead (Pb) and cadmium (Cd) were assayed as well. These hard tissues of the two species showed the following order of metal concentrations Zn>Fe>Pb>Cu>Cd. In scaup and pochard bones, the respective geometric mean concentrations of Zn, Fe, Pb, Cu, and Cd were 94.4 and 102.0; 20.2 and 24.7; 6.2 and 9.6; 0.19 and 0.26; 0.114 and 0.162 mg/kg. The levels of all the metals in cartilage (Zn 149.1 and 165.8; Fe 58.4 and 116.3; Pb 10.6 and 14.9; Cu 1.41 and 3.31; Cd 0.144 and 0.175 mg/kg, respectively) were higher than in the bones of A. marila and A. ferina. However, statistically significant differences were found in respect to the essential metals only (Zn, Fe, Cu). The inter-species comparisons showed the two species to differ in their cartilage concentrations of Fe, Cu, Zn, and Cd and in their bone concentrations of Pb and Cd. In each case, the pochard exhibited higher concentrations of metals. This study showed distinct differences between trace element accumulation by two heavily mineralised avian body parts: leg bones (tarsometatarsus) and cartilage (trachea). The results are in agreement with data reported by other workers who analysed trace metals in cartilaginous and bone components of the femoral head in homoiotherm vertebrates, including humans. Therefore it is important that intra- and inter-species comparisons of hard biological components be based on corresponding body parts, and that relevant biochemical and ecotoxicological research be pursued. PMID- 17854864 TI - Combining novel strategy with kinetic approach in the determination of respective respiration and skin exposure to N,N-dimethylformamide vapor. AB - N,N-dimethylformamide (DMF) could be readily absorbed via skin and inhalation routes. It is difficult, however, to separate the internal dose contribution from skin vapor and inhalation exposure. This study attempts to quantitatively determine the separate skin vapor and inhalation exposure contributions using a semi-actual exposure approach. Six volunteers were tailgated by DMF-exposed employees completely for two exposure scenarios: with and without wearing a respirator. Individual airborne DMF (A-DMF) exposure was evaluated by integrating real-time DMF monitoring and time-activity log. Urinary N-methylformamide (U-NMF) concentrations in 4-h and 8-h one urine sample plus 24-h consecutive urine sample were determined to evaluate the internal DMF exposure dose. The average A-DMF concentrations for all participants were 8.10 (2.75) and 9.52 (3.47) ppm, respectively, for with respirator and without respirator scenarios. Area under the curve of U-NMF throughout 24-h showed 71% and 29% contribution from skin and inhalation exposure, respectively, indicates that the absorbed dose of DMF via skin vapor exposure was much greater than inhalation. In conclusion, the semi actual approach provides a novel measure to accurately determine the relative skin vapor and inhalation exposure contributions to the internal dose. The skin vapor exposure deserves more attention in the prevention of chemical hazards in the exposed environment. PMID- 17854865 TI - Dysfibrinogen Kagoshima with the amino acid substitution gammaThr-314 to Ile: analyses of molecular abnormalities and thrombophilic nature of this abnormal molecule. AB - INTRODUCTION: Emerging lines of evidence have suggested that certain dysfibrinogens present a significant risk of thrombosis. PATIENT/METHODS: The thrombophilic nature of a new-type of dysfibrinogen Kagoshima identified in a 36 year-old female with deep vein thrombosis during the postpartum period was studied. RESULTS/DISCUSSION: Based on the analyses of the patient fibrinogen and the fibrinogen genes, fibrinogen Kagoshima was shown to have the amino acid substitution of gammaThr-314 to Ile that resulted in impaired function and hypofibrinogenemia. Polymerization of fibrin monomers derived from patient fibrinogen was severely impaired with a partial correction in the presence of calcium ions, causing very low clottability and delayed cross-linking of patient fibrin catalyzed by activated factor XIII. Because of the low clottability, a large amount of soluble fibrin was formed upon thrombin treatment, resulting in an increase of thrombin in the soluble fraction. Additionally, tPA-mediated plasmin generation on fibrin was impaired and calcium-ion-dependent integrity of the gamma-chain D domain of Kagoshima fibrinogen was perturbed. The presence of many tapered-fiber ends inside the tangled fibrin networks, observed by scanning electron microscopy, suggested early termination of fibrin polymerization and the structural alteration. CONCLUSION: These data suggest that fibrinogen Kagoshima is dysfunctional, giving rise to formation of fibrinolysis-resistant soluble fibrin polymers and entrance of soluble fibrin associating with thrombin to the circulation, partly accounting for the thrombophilic nature of the affected fibrinogen and fibrin molecules. PMID- 17854866 TI - Epidural hematoma following tissue plasminogen activator (tPA) therapy for pulmonary embolism in a pediatric patient with stage IV Burkitt's lymphoma: a case report. PMID- 17854867 TI - Ultrasound-enhanced tissue plasminogen activator thrombolysis in an in vitro porcine clot model. AB - INTRODUCTION: Thrombolytics such as recombinant tissue plasminogen activator (rt PA) have advanced the treatment of ischemic stroke, myocardial infarction, deep vein thrombosis and pulmonary embolism. OBJECTIVE: To improve the efficacy of this thrombolytic therapy, the synergistic effect of rt-PA and 120 kHz or 1.0 MHz ultrasound was assessed in vitro using a porcine clot model. MATERIALS AND METHODS: Fully retracted whole blood clots prepared from fresh porcine blood were employed to compare rt-PA thrombolytic treatment with and without exposure to 120 kHz or 1-MHz ultrasound. For sham studies (without ultrasound), clot mass loss was measured as a function of rt-PA concentration from 0.003 to 0.107 mg/ml. For combined ultrasound and rt-PA treatments, peak-to-peak pressure amplitudes of 0.35, 0.70 or 1.0 MPa were employed. The range of duty cycles varied from 10% to 100% (continuous wave) and the pulse repetition frequency was fixed at 1.7 KHz. RESULTS: For rt-PA alone, the mass loss increased monotonically as a function of rt-PA concentration up to approximately 0.050 mg/ml. With ultrasound and rt-PA exposure, clot mass loss increased by as much as 104% over rt-PA alone. Ultrasound without the presence of rt-PA did not significantly enhance thrombolysis compared to control treatment. The ultrasound-mediated clot mass loss enhancement increased with the square root of the overall treatment duration. CONCLUSIONS: Both 120-kHz and 1-MHz pulsed and CW ultrasound enhanced rt-PA thrombolysis in a porcine whole blood clot model in vitro. No clear dependence of the observed thrombolytic enhancement on ultrasound duty cycle was evident. The lack of duty cycle dependence suggests a more complex mechanism that could not be sustained by merely increasing the pulse duration. PMID- 17854869 TI - An overview of Notch3 function in vascular smooth muscle cells. AB - Proteins of the Notch family are cell surface receptors that transduce signals between neighbouring cells. The Notch signalling pathway is highly evolutionarily conserved and critical for cell fate determination during embryonic development, including many aspects of vascular development. The interaction of Notch receptors with ligands leads to cleavage of the Notch intracellular domain (NICD) which then translocates to the nucleus and activates the transcription factor CBF1/JBP-Jkappa, regulating downstream gene expression. To date four Notch receptors have been found in mammals. Of these, Notch3 is predominantly expressed in adult arterial smooth muscle cells in human. NOTCH3 gene mutations cause the autosomal dominant condition, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoecephelopathy (CADASIL), an inherited early stroke syndrome leading to dementia due to systemic vascular degeneration. This suggests that Notch3 plays a critical role in maintaining the phenotypic stability of vascular smooth muscle cells (VSMCs). Recent publications indicate that Notch3 is involved in vascular injury and is a determinant of VSMC survival, but its exact function is unknown. The molecular mechanisms underlying CADASIL pathology are therefore intriguing. Investigation of CADASIL mutant Notch3 shows that the majority of mutations do not change CBF1/JBP-Jkappa mediated classic Notch activation, so the pathological consequences of NOTCH3 mutations in CADASIL patients can not be simply explained by loss- or gain-of-function in the classic Notch signalling pathway. This suggests that a novel Notch3-mediated signalling pathway may be present in VSMCs, or cross-regulation of Notch3 to other signalling pathway(s) may play a critical role on VSMCs survival. Alternatively, the mutant Notch3 may gain a novel or toxic function in VSMCs. This review will focus on recent findings of Notch3 in vascular development and in regulating the VSMC behaviour and phenotype, and will use findings on investigating the molecular pathology of the single gene disorder CADASIL to understand the function of Notch3 in VSMCs. PMID- 17854870 TI - Survival impact of multiple bowel resections in patients undergoing primary cytoreductive surgery for advanced ovarian cancer: a case-control study. AB - OBJECTIVE: To evaluate clinicopathological factors and survival outcome of patients with advanced epithelial ovarian carcinoma undergoing multiple bowel resections to achieve optimal (< or = 1 cm) cytoreduction. METHODS: A case control study was performed identifying patients undergoing optimal primary cytoreductive surgery with > or = 2 bowel resections between 10/1997 and 2/2006. The two control groups consisted of (1) patients undergoing optimal cytoreduction with < or = 1 bowel resections matched [1:2] for age and stage and (2) patients left with suboptimal disease. Cox proportional hazards model were used to evaluate the effects of demographic and surgico-pathologic factors on survival outcome. RESULTS: A total of 34 patients underwent > or = 2 bowel resections. Sixty-eight patients underwent < or = 1 bowel resections. All patients had optimal cytoreduction and 40/102 patients (39.2%) underwent complete cytoreduction. Patients undergoing multiple bowel resections experienced a higher EBL (700 v 500 mL, p=0.01) and longer LOS (10 v 7 days, p=0.01) compared to patients with < or = 1 bowel resections. Multivariate analysis revealed the amount of residual disease to be a statistically significant and radiation therapy to the right pelvic sidewall and cul-de-sac independent predictor of overall survival. The median overall survival time for patients undergoing > or = 2 bowel resections was 28.3 months, which was comparable to patients undergoing < or = 1 bowel resections, (37.8 months, p=0.09) but statistically significantly superior to patients left with suboptimal residual disease (12 months, p=0.02). CONCLUSIONS: Although primary surgery that includes > or = 2 bowel resections is associated with longer LOS and a higher EBL, such extensive procedures are warranted if they will contribute to an overall optimal residual disease state. PMID- 17854868 TI - Late sodium current in failing heart: friend or foe? AB - Most cardiac Na+ channels open transiently upon membrane depolarization and then are quickly inactivated. However, some channels remain active, carrying the so called persistent or late Na+ current (INaL) throughout the action potential (AP) plateau. Experimental data and the results of numerical modeling accumulated over the past decade show the emerging importance of this late current component for the function of both normal and failing myocardium. INaL is produced by special gating modes of the cardiac-specific Na+ channel isoform. Heart failure (HF) slows channel gating and increases INaL, but HF-specific Na+ channel isoform underlying these changes has not been found. Na+ channels represent a multi protein complex and its activity is determined not only by the pore-forming alpha subunit but also by its auxiliary beta subunits, cytoskeleton, calmodulin, regulatory kinases and phosphatases, and trafficking proteins. Disruption of the integrity of this protein complex may lead to alterations of INaL in pathological conditions. Increased INaL and the corresponding Na+ flux in failing myocardium contribute to abnormal repolarization and an increased cell Ca2+ load. Interventions designed to correct INaL rescue normal repolarization and improve Ca2+ handling and contractility of the failing cardiomyocytes. This review considers (1) quantitative integration of INaL into the established electrophysiological and Ca2+ regulatory mechanisms in normal and failing cardiomyocytes and (2) a new therapeutic strategy utilizing a selective inhibition of INaL to target both arrhythmias and impaired contractility in HF. PMID- 17854871 TI - Antitumor activity of 4-(N-hydroxyphenyl)retinamide conjugated with poly(L glutamic acid) against ovarian cancer xenografts. AB - OBJECTIVE: Natural and synthetic retinoids such as N-(4-hydroxyphenyl)retinamide (4HPR) have been used for prevention and treatment of a variety of cancers; however, relapse usually occurs after treatment is stopped. Furthermore, the retinoid analogues are insoluble in water, making it difficult for systemic administration. The purpose of this study was to develop and evaluate a water soluble polymeric formulation of 4HPR that can release 4HPR over a period of a few days. METHODS: 4HPR was bound to a synthetic polyamino acid poly(L-glutamic acid) (PG). PG-4HPR was evaluated for its release kinetics and in vitro anti proliferative and in vivo antitumor activities against ovarian cancer cell lines. RESULTS: The release profile of PG-4HPR in phosphate buffered saline at 37 degrees C followed a first order kinetic, with a rate constant of 8.8x10(-3) h( 1). Approximately 60% of 4HPR was released over a period of 100 h. In vitro, both 4HPR and PG-4HPR inhibited proliferation of three ovarian cancer cells lines (SKOV3, OVCA420, and OVCA433) and an immortalized human ovarian epithelium cell line (IOSE) in a time- and dose-dependent manner. Increasing the exposure time of SKOV3 cells to both agents from 1 to 5 days resulted in an increased apoptotic response. In vivo, PG-4HPR demonstrated significantly enhanced antitumor activities compared to 4HPR in both early treatment and later treatment protocols. Treatments with PG-4HPR suppressed the expression of VEGF and reduced blood flow into the tumor. CONCLUSIONS: PG-4HPR may have potential applications in the prevention and therapy of ovarian cancers. PMID- 17854872 TI - Adenosquamous carcinoma versus adenocarcinoma in early-stage cervical cancer patients undergoing radical hysterectomy: an outcomes analysis. AB - OBJECTIVE: To evaluate whether histology (adenocarcinoma versus adenosquamous carcinoma) is an independent prognostic indicator in patients with stage IB1 cervical cancer after radical hysterectomy. METHODS: All patients with adenocarcinoma or adenosquamous carcinoma who underwent radical hysterectomy between October 1990 and December 2006 at The University of Texas M. D. Anderson Cancer Center were evaluated. Clinico-pathological data collected included age, disease stage, tumor grade, lymph node status, parametrial involvement, depth of invasion, evidence of lymph-vascular space invasion (LVSI), and adjuvant therapy. Patients were categorized as having "low-risk" or "high-risk" disease depending on the final pathologic findings. RESULTS: We identified 126 patients with stage IB1 adenosquamous (n=29) or adenocarcinoma (n=97) cervical cancer. The median follow-up was 79 months (range 1.7-184.6). The median age was 40.3 years for patients with adenocarcinoma and 35.2 years for patients with adenosquamous carcinoma (P=0.88). Grade III histology and LVSI were more common in patients with adenosquamous tumors than in patients with adenocarcinoma (85% versus 16%; P<0.01 and 56.5% versus 32.8; P=0.04). Histology was not associated with lymph node or parametrial involvement. There was no difference in recurrence rates between the two histologic groups, but the time to recurrence was shorter for patients with adenosquamous carcinoma (7.9 months versus 15 months; P=0.01). There was no difference between cell types with regards to recurrence and recurrence-free survival rates in the low- and high-risk groups. CONCLUSION: We found no evidence that histologic subtype affects outcome; however, the median time to recurrence was shorter in patients with adenosquamous carcinoma. Our study suggests that in patients with stage IB1 adenosquamous carcinoma or adenocarcinoma, the presence of high-risk features is more important than histologic subtype. PMID- 17854873 TI - Human papillomavirus DNA detection in ThinPrep Pap test vials is independent of cytologic sampling of the transformation zone. AB - OBJECTIVE: Sampling of the transformation zone (TZ) and endocervical cells (EC) has been widely regarded as a quality indicator in cervical screening programs; however, the significance of a TZ/EC sample (TZ/ECS) in promoting disease detection remains a matter of controversy. Because little data are available on the relationship between TZ/EC sampling and HPV DNA test results, we examined whether or not there is a measurable association between high-risk human papillomavirus (hrHPV) DNA test results and TZ/EC sampling in several thousand women screened in a large academic women's hospital laboratory. METHODS: 9035 ThinPrep Pap tests (TPPT) reported as negative, LSIL, or HSIL and which also had Hybrid capture 2 (HC2) hrHPV DNA testing over an 18 month period between July 1, 2005 and December 31, 2006 were documented. 8415 negative, 526 LSIL, and 84 HSIL TPPT were included in the study. The age of patients, the presence or absence of a TZ/ECS, and hrHPV DNA test results were noted from CoPath data files. Patients were stratified into 10 year age groups for data analysis. RESULTS: An identical 2.8% of Pap negative patients were hrHPV DNA positive in both the 6709 cytology negative patients with a TZ/ECS and the 1706 cytology negative patients without a TZ/ECS. Neither were statistically significant differences noted for hrHPV DNA prevalence in patients with SIL Pap test results from women with and without a TZ/ECS. CONCLUSIONS: HC2 hrHPV DNA detection in TPPT vials is independent of cytologic sampling of the transformation zone. hrHPV DNA results provide for the first time an available objective basis for risk assessment of patients with no TZ/ECS. The observation that hrHPV DNA test status is independent of presence or absence of a TZ/ECS is consistent with longitudinal studies of Pap negative women with no TZ/ECS which have not found increased disease on follow-up. PMID- 17854874 TI - Antinociceptive effects of systemic paeoniflorin on bee venom-induced various 'phenotypes' of nociception and hypersensitivity. AB - Paeoniflorin (PF), one of the active chemical compounds identified from the root of Paeonia lactiflora Pall, has been well-established to exhibit various neuroprotective actions in the central nervous system (CNS) after long-term daily administration. In the present study, by using the bee venom (BV) model of nociception and hypersensitivity, antinociceptive effects of PF were evaluated by intraperitoneal administration in conscious rats. When compared with saline control, systemic pre- and post-treatment with PF resulted in an apparent antinociception against both persistent spontaneous nociception and primary heat hypersensitivity, while for the primary mechanical hypersensitivity only pre treatment was effective. Moreover, pre- and early post-treatment with PF (5 min after BV injection) could successfully suppress the occurrence and maintenance of the mirror-image heat hypersensitivity, whereas late post-treatment (3 h after BV) did not exert any significant impact. In the Rota-Rod treadmill test, PF administration did not affect the motor coordinating performance of rats. Furthermore, systemic PF application produced no significant influence upon BV induced paw edema and swelling. Finally, the PF-produced antinociception was likely to be mediated by endogenous opioid receptors because of its naloxone reversibility. Taken together, these results provide a new line of evidence showing that PF, besides its well-established neuroprotective actions in the CNS, is also able to produce analgesia against various 'phenotypes' of nociception and hypersensitivity via opioid receptor mediation. PMID- 17854875 TI - Milnacipran attenuates hyperalgesia and potentiates antihyperalgesic effect of tramadol in rats with mononeuropathic pain. AB - Milnacipran is a non-tricyclic antidepressant drug which selectively inhibits serotonin and noradrenaline re-uptake and is recommended in the treatment of various chronic pain syndromes. Many studies have shown that compounds known to block monoamine uptake potentiate the antinociceptive effects of opioids. This study investigates the effect of milnacipran alone or in combination with an opiodergic drug, i.e. tramadol, on hyperalgesia in a rat model of neuropathic pain. The contribution of serotonergic, noradrenergic and opioidergic systems in the potential antihyperalgesic effect of milnacipran has also been examined. Chronic constriction injury was induced in rats by loose ligation of the sciatic nerve and neuropathic pain was evaluated 14 days after surgery. Intraperitoneal acute injection of milnacipran 60 mg/kg produced an antihyperalgesic effect which was prevented by pretreating systemically with alpha-methyl-p-tyrosine, an inhibitor of noradrenaline synthesis; parachlorophenylalanine, an inhibitor of serotonin synthesis; and naloxone, an antagonist of opioidergic receptors. Co administration of milnacipran 40 mg/kg with tramadol (20 and 40 mg/kg) potentiated the antihyperalgesic effect of tramadol. Milnacipran has an antihyperalgesic effect mediated by serotonergic, noradrenergic and opioidergic systems and the combined use of tramadol with milnacipran potentiates the effect of tramadol in the management of neuropathic pain. PMID- 17854876 TI - The effects of concurrent administration of +/-3,4-methylenedioxymethamphetamine and cocaine on conditioned place preference in the adult male rat. AB - Conditioned place preference (CPP), a commonly used model for studying the role of contextual cues in drug reward and drug seeking, was employed to explore possible behavioral interactions between (+/-)3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") and cocaine. On each of four occasions, adult male rats received one of three doses of MDMA (0 mg/kg, 5 mg/kg, 10 mg/kg; administered subcutaneously [s.c.]) combined with one of three doses of cocaine (0 mg/kg, 2.5 mg/kg, 5 mg/kg; administered intraperitoneally [i.p.]), and were then tested in a CPP paradigm. The results showed MDMA-induced CPP at a unit dose of 5 mg/kg, but at the 10 mg/kg dose there was a return to baseline (control) performance levels. For cocaine alone, CPP increased in a linear fashion as the drug dose was increased. Concurrent administration resulted in antagonism of each drug, but there was evidence that this pattern was reversible at higher doses of the respective drugs. These data are instructive insofar as they suggest that the behavioral and neurochemical effects of MDMA and cocaine presented in isolation are dramatically altered when the two drugs are presented in combination. PMID- 17854877 TI - Long-term follow-up of patients with primary immunodeficiencies. AB - As an example of the need for long-term follow-up by specialty health care to adequately manage immunodeficient patients, we report the case of a patient with Wiskott-Aldrich syndrome who was lost to follow-up for 4 years to the immunology clinic and came back with a neck mass that was diagnosed as B-cell lymphoma. Patients with immunodeficiency are at high risk for the development of malignancy and autoimmune diseases and should be evaluated by a trained specialist with a frequency of not less than every 6 months. PMID- 17854878 TI - Successful haploidentical bone marrow transplantation in a patient with reticular dysgenesis: three-year follow-up. PMID- 17854879 TI - Nonwoven in contrast to woven mattress encasings accumulate mite and cat allergen. PMID- 17854881 TI - Omalizumab for drug allergy. PMID- 17854882 TI - Influence of early day-care exposure on total IgE levels through age 3 years. AB - BACKGROUND: Early day care is inversely associated with asthma and atopy in later childhood, but its association with early immunologic markers of asthma risk is not known. OBJECTIVE: We sought to assess the relation of day care by 3 months to total IgE levels through age 3 years. METHODS: Day care was assessed prospectively among 362 nonselected infants enrolled in the Infant Immune Study. Children were categorized based on day-care status by 3 months of age as follows: no day care, day care inside the home with other children, day care outside the home with no other children, or day care outside the home with other children. Total IgE levels were measured in blood obtained at 3, 12, 24, and 36 months. Relations between day care and IgE levels were assessed at each age and longitudinally, with stratification by maternal asthma and atopy. RESULTS: Day care by 3 months was associated with decreased IgE levels through age 3 years (coefficient: -0.19 log IU/mL, P = .001). The greatest effect was evident for children cared for outside the home. Stratified analyses indicated that the relation existed primarily among children who had atopic or asthmatic mothers. Day-care entry after 3 months showed no relation with IgE levels. CONCLUSION: Day care attendance by 3 months is associated with decreased total IgE levels in the first 3 years of life in children of mothers who are atopic, asthmatic, or both. CLINICAL IMPLICATIONS: Early day-care exposure can reduce IgE levels, which in turn might reflect a reduced risk of allergic disease in predisposed children. PMID- 17854883 TI - Protection against abortion linked to gamma interferon production in pregnant dairy cows naturally infected with Neospora caninum. AB - Many immunological aspects of pregnancy, such as the role played by gamma interferon (IFN-gamma) in abortion, are not well understood. Neospora caninum is an intracellular protozoan considered to be among the main causes of abortion in cattle worldwide. The present study analyzes the interaction between IFN-gamma production and N. caninum infection in naturally infected pregnant cows. Data were obtained from 126 pregnant cows: 86 seropositive and 40 seronegative for the parasite. Pregnancy diagnosis and blood sample collection were performed on days 40, 90, 120, 150, 180 and 210 post-insemination or until the time of abortion detection. Plasma was tested for antibodies against N. caninum and IFN-gamma. Interferon-gamma was detected at some point along the pregnancy in 16 (19%) of the 86 Neospora-seropositive cows yet was undetectable in the 40 seronegative animals. Of the 126 pregnancies examined, 22 (17.5%) ended in abortion. Abortion occurred in 24.4% of seropositive cows (21/86) and in 2.5% of seronegative animals (1/40). Significant (P<0.0001) interaction was observed between Neospora seropositivity and IFN-gamma production. Based on the odds ratio, the risk of abortion was 15.6 times higher in seropositive cows not producing IFN-gamma than in seronegative animals, whereas neosporosis had no effect in seropositive cows with IFN-gamma production. A significant (P=0.001) negative effect of IFN-gamma production on the Neospora titer was furthermore observed in the 65 non-aborting seropositive animals. These results indicate that IFN-gamma production affords protection against abortion in Neospora-infected cows and also point to a reduced humoral immune response to N. caninum during gestation in cows producing IFN gamma. PMID- 17854884 TI - Ovulation induced by mucosa vaginal absorption of buserelin and triptorelin in rabbit. AB - The aim of this study was to evaluate the supplementation of semen extender with two synthetic GnRH analogues (buserelin and triptorelin) to induce ovulation in rabbit does submitted to artificial insemination. In a first experiment, 255 receptive multiparous does were inseminated with 0.5 mL of Tris-citrate-glucose extender supplemented or not with two GnRH synthetic analogues. Experimental groups were: NC (not supplemented extender), PC (not supplemented extender and does treated with 1 microg of buserelin i.m.), B2 (2 microg per female buserelin supplemented extender), B5 (5 microg per female buserelin supplemented extender), T2 (2 microg per female triptorelin supplemented extender) and T5 (5 microg per female triptorelin supplemented extender). Thirteen does of NC females ovulated, reaching an ovulation rate similar to the other groups. Ovulation rate was similar in all groups (11.4-12.5). The efficiency of ovulation induction was very low (32.5%) in NC group and showed the higher results in PC females (97.8%). Only B5 females reached similar ovulation induction response than PC group. In a second experiment, 702 receptive does were inseminated to compare fertility and prolificacy parameters from the conventional insemination technique (control group, females treated with 1 microg per female of buserelin intramuscularly) versus a supplementation with buserelin or triptorelin (5 microg per female) in semen extender (B5 and T5 groups, respectively). Fertility and prolificacy parameters were similar among the groups (77.8% fertility rate, 73.9% kindling rate, 9.4 live born and 9.9 total born). This study demonstrate the possibility of ovulation induction in rabbits by adding two GnRH synthetic analogues in the seminal doses and open up new prospects for changing rabbit insemination procedures. PMID- 17854885 TI - Maternal and neonatal tetanus. AB - Maternal and neonatal tetanus are important causes of maternal and neonatal mortality, claiming about 180 000 lives worldwide every year, almost exclusively in developing countries. Although easily prevented by maternal immunisation with tetanus toxoid vaccine, and aseptic obstetric and postnatal umbilical-cord care practices, maternal and neonatal tetanus persist as public-health problems in 48 countries, mainly in Asia and Africa. Survival of tetanus patients has improved substantially for those treated in hospitals with modern intensive-care facilities; however, such facilities are often unavailable where the tetanus burden is highest. The Maternal and Neonatal Tetanus Elimination Initiative assists countries in which maternal and neonatal tetanus has not been eliminated to provide immunisation with tetanus toxoid to women of childbearing age. The ultimate goal of this initiative is the worldwide elimination of maternal and neonatal tetanus. Since tetanus spores cannot be removed from the environment, sustaining elimination will require improvements to presently inadequate immunisation and health-service infrastructures, and universal access to those services. The renewed worldwide commitment to the reduction of maternal and child mortality, if translated into effective action, could help to provide the systemic changes needed for long-term elimination of maternal and neonatal tetanus. PMID- 17854886 TI - Tetanus toxin C fragment-conjugated nanoparticles for targeted drug delivery to neurons. AB - The use of nanoparticles for targeted drug delivery is often facilitated by specific conjugation of functional targeting molecules to the nanoparticle surface. We compared different biotin-binding proteins (avidin, streptavidin, or neutravidin) as crosslinkers to conjugate proteins to biodegradable nanoparticles prepared from poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG) biotin polymers. Avidin gave the highest levels of overall protein conjugation, whereas neutravidin minimized protein non-specific binding to the polymer. The tetanus toxin C fragment (TTC), which is efficiently retrogradely transported in neurons and binds to neurons with high specificity and affinity, retained the ability to bind to neuroblastoma cells following amine group modifications. TTC was conjugated to nanoparticles using neutravidin, and the resulting nanoparticles were shown to selectively target neuroblastoma cells in vitro. TTC conjugated nanoparticles have the potential to serve as drug delivery vehicles targeted to the central nervous system. PMID- 17854887 TI - Cartilage repair using an in vitro generated scaffold-free tissue-engineered construct derived from porcine synovial mesenchymal stem cells. AB - The objective was to in vitro generate a mesenchymal stem cell (MSC)-based tissue engineered construct (TEC) to facilitate in vivo repair in a porcine chondral defect model. Porcine synovial MSCs were cultured in monolayer at high density and were subsequently detached from the substratum. The cell/matrix complex spontaneously contracted to develop a basic TEC. Immunohistochemical analysis showed that the basic TEC contained collagen I and III, fibronectin, and vitronectin. The basic TEC exhibited stable adhesion to the surface of a porcine cartilage matrix in an explant culture system. The TEC cultured in chondrogenic media exhibited elevated expression of glycosaminoglycan and chondrogenic marker genes. The TEC were implanted in vivo into chondral defects in the medial femoral condyle of 4-month-old pigs, followed by sacrifice after 6 months. Implantation of a TEC into chondral defects initiated repair with a chondrogenic-like tissue, as well as secure biological integration to the adjacent cartilage. Histologically, the repair tissue stained positively with Safranin O and for collagen II. Biomechanical evaluation revealed that repair tissue exhibited mechanical properties similar to those of normal porcine cartilage in static compression and friction tests. This technology is a unique and promising method for stem cell-based cartilage repair. PMID- 17854888 TI - Ca(2+)/Calmodulin-binding proteins from the C. elegans proteome. AB - Calmodulin (CaM) is the primary Ca(2+)-sensor that regulates a wide variety of cellular processes in eukaryotes. Although many Ca(2+)/CaM-binding proteins have been identified, very few such proteins could be found from the genome-wide protein-protein interaction maps of Caenorhabditis elegans constructed by yeast two-hybrid screening. Using a genotype-phenotype conjugation method called mRNA display, we performed a selection for Ca(2+)/CaM-binding proteins from a proteome library of C. elegans. The method allowed the identification of 9 known and 47 previously uncharacterized Ca(2+)-dependent CaM-binding proteins from the adult worm proteome. The Ca(2+)/CaM-binding properties of these proteins were characterized and their binding motifs were identified. The availability of such information could facilitate our understanding of the signaling pathways mediated by Ca(2+)/CaM in C. elegans. Due to its simplicity and efficiency, the method could be readily applied to examine the Ca(2+)-dependent binding partners of numerous other Ca(2+)-binding proteins, which may play important roles in many signaling pathways in C. elegans. PMID- 17854889 TI - A fast Ca2+-induced Ca2+-release mechanism in Dictyostelium discoideum. AB - In vertebrate cells calcium-induced calcium release (CICR) is thought to be responsible for rapid cytosolic Ca(2+) elevations despite the occurrence of strong Ca(2+) buffering within the cytosol. In Dictyostelium, a CICR mechanism has not been reported. While analyzing Ca(2+) regulation in a vesicular fraction of Dictyostelium rich in Ca(2+)-flux activity, containing contractile vacuoles (CV) as the main component of acidic Ca(2+) stores and ER, we detected a rapid Ca(2+) change upon addition of Ca(2+) (CIC). CIC was three times larger in active stores accumulating Ca(2+) than before Ca(2+) uptake and in inactivated stores. Ca(2+) release was demonstrated with the calmodulin antagonist W7 that inhibits the V-type H(+)ATPase activity and Ca(2+) uptake of acidic Ca(2+) stores. W7 caused a rapid and large increase of extravesicular Ca(2+) ([Ca(2+)](e)), much faster and larger than thapsigargin (Tg), a Ca(2+)-uptake inhibitor of the ER. W7 treatment blocked CIC indicating that a large part of CIC is due to Ca(2+) release. The height of CIC depended on the filling state of the Ca(2+) stores. CIC was virtually unchanged in the iplA(-) strain that lacks a putative IP(3) or ryanodine receptor thought to be located at the endoplasmic reticulum. By contrast, CIC was reduced in two mutants, HGR8 and lvsA(-), that are impaired in acidic Ca(2+)-store function. Purified Ca(2+) stores enriched in CV still displayed CIC, indicating that CV are a source of Ca(2+)-induced Ca(2+) release. CIC-defective mutants were altered in their oscillatory properties. The irregularity of the HGR8 oscillation suggests that the principal oscillator is affected in this mutant. PMID- 17854890 TI - Modulatory role of neuropeptide FF system in nociception and opiate analgesia. AB - The tetra-peptide FMRF-NH(2) is a cardioexcitatory peptide in the clam. Using the antibody against this peptide, FMRF-NH(2)-like immunoreactive material was detected in mammalian CNS. Subsequently, mammalian FMRF-NH(2) immunoreactive peptides were isolated from bovine brain and characterized to be FLFQPQRF-NH(2) (NPFF) and AGEGLSSPFWSLAAPQRF-NH(2) (NPAF). The genes encoding NPFF precursor proteins and NPFF receptors 1 and 2 are expressed in all vertebrate species examined to date and are highly conserved. Among many biological roles suggested for the NPFF system, the possible modulatory role of NPFF in nocicetion and opiate analgesia has been most widely investigated. Pharmacologically, NPFF related peptides were found to exhibit analgesia and also potentiate the analgesic activity of opiates when administered intrathecally but attenuate the opiate induced analgesia when administered intracerebroventricularly. RF-NH(2) peptides including NPFF-related peptides were found to delay the rate of acid sensing ion channels (ASIC) desensitization resulting in enhancing acid gated currents, raising the possibility that NPFF also may have a pain modulatory role through ASIC. The genes for NPFF as well as NPFF-R2, preferred receptor for NPFF, are highly unevenly expressed in the rat CNS with the highest levels localized to the superficial layers of the dorsal spinal cord. These two genes are also present in the dorsal root ganglia (DRG), though at low levels in normal rats. NPFF and NPFF-R2 mRNAs were found to be coordinately up-regulated in spinal cord and DRG of rats with peripheral inflammation. In addition, NPFF-R2 immunoreactivity in the primary afferents was increased by peripheral inflammation. The findings from the early studies on the analgesic and morphine modulating activities suggested a role for NPFF in pain modulation and this possibility is further supported by the distribution of NPFF and its receptor and the regulation of the NPFF system in vivo. PMID- 17854891 TI - A case of Philadelphia-chromosome positive chronic idiopathic myelofibrosis. AB - Philadelphia-chromosome positive thrombocythemia without features of chronic myeloid leukemia in peripheral blood has been described before. However, there are few reports on Philadelphia-chromosome positive chronic idiopathic myelofibrosis. We present a case of Philadelphia positive chronic idiopathic myelofibrosis that had no obvious response to imatinib. PMID- 17854892 TI - Sero-prevalence of bovine Johne's disease in buffaloes and cattle population of North India using indigenous ELISA kit based on native Mycobacterium avium subspecies paratuberculosis 'Bison type' genotype of goat origin. AB - Present pilot study is the first attempt in the country to estimate sero prevalence of Bovine Johne's disease (BJD) by screening cattle and buffaloes representing large population belonging to farmer's and farm herds in the home tracts (Uttar Pradesh (UP) and Punjab) of Hariana cattle and Murrah buffaloes in North India. Indigenous and in-house plate ELISA kit (using protoplasmic antigen from native Mycobacterium avium subsp. paratuberculosis 'Bison type' strain of goat origin), originally developed for goats and sheep was standardized in bovines and used for screening. For this study, 33 villages of south and west UP were randomly selected and surveyed from 2001 to 2003. There were 7943 farmer's families having 38,251 livestock, including cattle, buffaloes, goats and sheep (per family 4.8% livestock). Numerically, buffaloes and cattle were 54.7% and 22.1%, respectively. Serum samples were collected from 726 animals (4.2% of 16, 981 livestock with 4375 farmer's families) located in 33 randomly surveyed villages. Serum samples (699), submitted to Epidemiology Department of Veterinary College (Punjab Agricultural University, Ludhiana), in the year 2004 by farmer's and organized farm herds (Buffaloes, 372, Cattle, 327), were screened by this ELISA kit. Soluble protoplasmic antigen was prepared from Map (S 5) 'Bison type' strain isolated from a terminally sick goat with Johne's disease. Of the total 1425 bovine (Buffaloes and cattle) serum samples screened using indigenous ELISA kit, sero-prevalence of Johne's disease was 29.0% (28.6% in buffalo and 29.8% in cattle) in Northern India. State-wise sero-prevalence was 31.9% and 23.3% in UP and Punjab, respectively. In UP, of the 601 randomly sampled buffaloes, sero prevalence was 40.3% (16.6% in young and 40.9% adults) and 25.5% (10.5% in young and 26.3% adults) in south and west UP, respectively. Of the 125 cattle screened, sero-prevalence was 42.6% (nil in young and 44.4% adults) and 30.0% (nil in young and 30.6% adults) in south and west UP, respectively. Of the 699 serum samples screened from Ludhiana, Punjab, sero-prevalence of BJD was 23.0%. Sero-prevalence was 23.3% (12.1% in young and 24.4% in adults) and 26.9% (27.2% in young and 26.8% in adults) in buffaloes and cattle, respectively. High prevalence of BJD in buffaloes in native tract of Murrah breed, and Hariana breed of cattle correlated with poor per-animal productivity and BJD may be the major cause. Indigenous ELISA kit was rapid, economic and sensitive test for large-scale screening of buffaloes and cattle population against incurable BJD. PMID- 17854893 TI - Learning strategies in amnesia. AB - Previous research suggests that early performance of amnesic individuals in a probabilistic category learning task is relatively unimpaired. When combined with impaired declarative knowledge, this is taken as evidence for the existence of separate implicit and explicit memory systems. The present study contains a more fine-grained analysis of learning than earlier studies. Using a dynamic lens model approach with plausible learning models, we found that the learning process is indeed indistinguishable between an amnesic and control group. However, in contrast to earlier findings, we found that explicit knowledge of the task structure is also good in both the amnesic and the control group. This is inconsistent with a crucial prediction from the multiple-systems account. The results can be explained from a single system account and previously found differences in later categorization performance can be accounted for by a difference in learning rate. PMID- 17854894 TI - Anatomy and physiology of the basal ganglia: implications for DBS in psychiatry. AB - The basal ganglia have been a target for neuromodulation surgery since Russell Meyers' pioneering works in the late 1930s. Contemporary movement disorder surgery on the brain has evolved from empiric observations on movement behavior after neurological lesions. So too has the development of psychiatric surgical procedures followed the observation of lesions in the brain on cognitive and affective behavior. Just as deep brain stimulation (DBS) has revolutionized the practice of movement disorder surgery, its application to psychiatric illness has become the cutting edge of functional and restorative neurosurgery. The fundamental concept of the cortico-striatal-pallido-thalamocortical loop will be explored in the context of psychiatric disorders. DBS targeting this circuitry appears from initial evidence in obsessive-compulsive disorder (OCD) to be a promising option for patients with neuropsychiatric illness resistant to conventional therapies. Further exploring the anatomic interconnectivity of the physiologically relevant cortical and subcortical areas will inevitably lead to better applications of DBS for the treatment of OCD, major depression (MD) and potentially for other psychiatric disorders. Implementing such therapies optimally will require the creation of treatment centers with specialized expertise in the psychiatric, neurosurgical, and ethical issues that arise with these populations. PMID- 17854895 TI - Interactive memory systems and category learning in schizophrenia. AB - Schizophrenia is a devastating mental disorder with multiple facets, including the impairment of learning and memory. Recent evidence suggests that information is processed and represented by multiple interacting memory systems in the brain, including prefrontal cortex, basal ganglia, and medial temporal lobe. These structures are critical in the pathophysiology of schizophrenia. Whereas executive and declarative memory dysfunctions are well known in schizophrenia, habit learning deficits related to the basal ganglia are less clear, despite the fact that dopaminergic and other neurochemical processes in the basal ganglia may play a crucial role in the pathophysiology and pharmacology of schizophrenia. In this article, I propose that the investigation of different classification learning functions, including reward- and feedback-guided learning and acquired equivalence learning, may shed light on the neuropsychology, pathophysiology, pharmacology, and behavioral genetics of schizophrenia. PMID- 17854896 TI - Exploring uncertainty of the change from ICD-9 to ICD-10 on acute mortality effects of air pollution. AB - The change in ICD coding from ICD-9 to ICD-10 may produce inconsistencies and discontinuities in cause-specific mortality, thus impacting on effects estimates of air pollution on mortality. The current study was conducted in Wuhan, China. We examined the concordant rates and Kappa statistics using the mortality data from the year 2002 coded with both ICD-9 and ICD-10 codes and compared the estimated effects of air pollution using the Generalized Additive Model in R. We found high concordant rates (>99.3%) and Kappa statistics close to 1.0 (>0.98). Little difference was identified in the estimated effects of air pollution on daily cardiovascular, stroke, cardiac, cardiopulmonary, and respiratory mortality. This study provides evidence that, based on the wide definitions of cause-specific morality typically used in the studies of time-series air pollution mortality, the change in the ICD coding does not significantly affect the estimated effects of air pollution. PMID- 17854897 TI - The 2'-5'-oligoadenylate synthetase in the lowest metazoa: isolation, cloning, expression and functional activity in the sponge Lubomirskia baicalensis. AB - Aquatic animals, especially filter feeders such as sponges [phylum Porifera], are exposed to a higher viral load than terrestrial species. Until now, the antiviral defense system in the evolutionary oldest multicellular organisms, sponges, is not understood. One powerful protection of vertebrates against virus infection is mediated by the interferon (IFN)-inducible 2'-5'-oligoadenylate synthetase [(2 5)A synthetase] system. In the present study we cloned from the freshwater sponge Lubomirskia baicalensis a cDNA encoding a 314 aa long ORF with a calculated size of 35748Da, a putative (2-5)A synthetase, and raised antibodies against the recombinant protein. The native enzyme was identified in a crude extract from L. baicalensis by application of a novel separation procedure based on polymer coated ferromagnetic nanoparticles. The particles were derivatized with a synthetic double-stranded RNA [dsRNA], synthetic poly(I:C), a known allosteric activator of the latent (2-5)A synthetase. These particles were used to separate a single 35kDa protein from a crude extract of L. baicalensis, which cross reacted with antibodies raised against the sponge enzyme. In situ hybridization studies revealed that highest expression of the gene is seen in cells surrounding the aquiferous canals. Finally primmorphs, an in vitro cell culture system, from L. baicalensis were exposed to poly(I:C); they responded to this dsRNA with an increased expression of the (2-5)A synthetase gene already after a 1-day incubation period. We conclude that sponges contain the (2-5)A synthetase antiviral protection system. PMID- 17854898 TI - Identification of a new cis-regulatory element of the terminal deoxynucleotidyl transferase gene in the 5' region of the murine locus. AB - Terminal deoxynucleotidyl transferase (TdT) expression is controlled at the transcriptional level, however, the TdT core promoter combining D, D', an initiator (Inr) and downstream basal elements (DBE) does not recapitulate the whole complex regulation of TdT expression. We hypothesized that important cis regulatory elements of the gene are located outside of the TdT promoter. In an attempt to identify these elements, we performed DNase I hypersensitivity assays over 24kb including a 10kb region located upstream of the transcription start site (+1) and a 14kb region spanning exons and introns I to VI. Hypersensitive sites (HS) HS1 and HS2 were localized 8.5 and 8kb upstream of the transcription start site, respectively, and were exclusively detected in TdT+ cell types. HS3, HS4 and HS5 were mapped at positions -7, -3.4 and -3kb, respectively, and detected in both TdT negative and positive cells. HS6, HS7 and HS8 were detected immediately upstream of the TdT promoter. HS10 and HS11 were localized in the first and third intron of the gene. Luciferase reporter assays revealed that HS1, HS2 and HS3 synergize with the TdT promoter to activate transcription in a TdT+ pre-T cell line but not in a TdT+ pro-B cell line. In summary novel cis regulatory elements have been identified in the 5' region of the TdT locus that synergize with the promoter to activate gene expression and our results suggest these elements may be more active in T cells. PMID- 17854899 TI - Resolution of retinoschisis after vitreous surgery in X-linked retinoschisis. AB - PURPOSE: To describe the efficacy of vitreous surgery to treat X-linked retinoschisis. DESIGN: Retrospective, comparative, interventional case series. PARTICIPANTS: Three patients (5 eyes) had foveal retinoschisis with peripheral retinoschisis. The patients' ages were 26, 7, and 17 years at the first surgery. The preoperative best-corrected visual acuity (BCVA) was 20/100 and 20/40 in patient 1, 20/30 in patient 2, and 20/100 and 20/200 in patient 3. METHODS: The vitreous surgery consisted of core vitrectomy, surgically induced posterior vitreous detachment (PVD), removal of the internal limiting membrane (except for the right eye of patient 1), and 30% sulfur hexafluoride gas tamponade. The follow-up periods ranged from 6 months to 12 years. MAIN OUTCOME MEASURES: Best corrected visual acuity and retinal tomography monitored by optical coherence tomography. RESULTS: Restoration of the foveal depression with collapse of the schisis cavity was achieved with the first surgery in 4 (80%) of the 5 eyes. In the right eye of patient 1, the retinoschisis persisted after the first surgery because of failed surgically induced PVD; the retinoschisis resolved promptly after the second surgery with successful induction of PVD. The BCVA improved in 3 eyes and was unchanged in 2 eyes. CONCLUSIONS: Vitreous surgery resulted in reattachment of the retinoschisis with visual improvement. Vitreous traction may play a role in the development of foveal retinoschisis. PMID- 17854900 TI - Exposure rate of hydroxyapatite orbital implants a 15-year experience of 802 cases. AB - OBJECTIVE: To document the long-term experience with hydroxyapatite (HA) orbital implants (Bio-Eye) and analyze the factors influencing implant exposure, including surgical type, procedural modification, use of different wrapping materials and peg materials. DESIGN: Retrospective observational case series. PARTICIPANTS: Eight hundred two eyes from 802 patients who underwent anophthalmic socket surgery (eviscerations, enucleations, secondary implant placements) using HA implants, performed by one surgeon between May 1990 and December 2005. METHODS: All patients' clinical records were reviewed. Baseline age, cause of anophthalmic surgery, surgical type, size of HA implant, wrapping material, and peg system were recorded. MAIN OUTCOME MEASURES: Postoperative complications, especially implant exposure, were recorded separately before and after pegging, and compared according to type of surgery, wrapping material, and peg system. RESULTS: The main cause of anophthalmic surgery was trauma (73%). A variety of wrapping materials have been used, including Tutoplast-dura, Vicryl mesh, autogenous sclera, and polyester-urethane. Implant exposure occurred in 17 patients (2.1%) before pegging and 14 (4.0%) after pegging. The exposure rate was significantly higher in eyes eviscerated without (7.2%) than with (1.1%) keratectomy (P = 0.018), but did not differ according to type of surgery (P = 0.710). When distributed according to 5-year periods, the exposure rate was higher from 1990 to 1994 (4.7%) than in later periods (P = 0.004). In patients who underwent enucleation or secondary implantation, there was no difference in exposure rate between Tutoplast-dura- and Vicryl mesh-wrapped implants (P = 0.235). Among the 353 patients (44.0%) who underwent pegging, those who received titanium-pegged implants had a significantly lower incidence of peg extrusion (5.2%), major discharge (5.2%), and pyogenic granuloma (9.1%) than those with nonsleeved polymethyl methacrylate and sleeved polycarbonate peg materials (P<0.05). CONCLUSIONS: Exposures associated with HA orbital implants decreased with the improvement of surgical technique over time and have been managed successfully, both before and after pegging. The incidence of peg-related complications have decreased since the introduction of the titanium peg system. PMID- 17854901 TI - Detrimental effects of post-treatment with fatty acids on brain injury in ischemic rats. AB - Studies have illustrated that fatty acids, especially polyunsaturated fatty acids (PUFA), have a role in regulating oxidative stress via the enhancement of antioxidative defense capacity or the augmentation of oxidative burden. Elevated oxidative stress has been implicated in the pathogenesis of brain injury associated with cerebral ischemia/reperfusion (I/R). The objective of this study was to assess whether treatment with fatty acids after focal cerebral I/R induced by occlusion of the common carotid arteries and the middle cerebral artery has effects on brain injury in a rat model. PUFA, including arachidonic acid (AA) and docosahexaenoic acid (DHA), and the saturated fatty acid, stearic acid (SA), were administrated 60 min after reperfusion via intraperitoneal injection. AA and DHA aggravated cerebral ischemic injury, which manifested as enlargement of areas of cerebral infarction and increased impairment of motor activity, in a concentration-dependent manner. However, there were no remarkable differences in post-ischemic alterations between the SA and saline groups. The post-ischemic augmentation of injury in AA and DHA treatment groups was accompanied by increases in the permeability of the blood-brain barrier (BBB), brain edema, metalloproteinase (MMP) activity, inflammatory cell infiltration, cyclooxygenase 2 (COX-2) expression, caspase 3 activity, and malondialdehyde (MDA) production, and by a decrease in the brain glutathione (GSH) content. Furthermore, we found that either AA or DHA alone had little effect on free radical generation in neuroglia, but they greatly increased the hydrogen peroxide-induced oxidative burden. Taken together, these findings demonstrate the detrimental effect of PUFA such as AA and DHA in post-ischemic progression and brain injury after cerebral I/R is associated with augmentation of cerebral I/R-induced alterations, including oxidative changes. PMID- 17854902 TI - Potentiometric and spectrophotometric equilibrium study on Fe(III) and new catechol-bisphosphonate conjugates. AB - The coordination properties of mixed catechol-bisphosphonates towards Fe(III) are presented. From the potentiometric and spectroscopic results it was possible to state that iron coordination takes place only on the bisphosphonate moiety at acidic pH, and involves both catechol and bisphosphonate groups on two different iron(III) ions at higher pH values. Steric constracts keep both groups from chelating the same metal ion. Quantum mechanical calculations confirm this statement and allow to determine the minimum length of the linker for a stable conformation of complexes in which the same iron(III) ion is coordinated by both catechol and bisphosphonate. PMID- 17854903 TI - Molecular characterization of recent Vibrio cholerae O1, El Tor, Inaba strains isolated from hospitalized patients in Kolkata, India. AB - OBJECTIVES: To study the phenotypic and genotypic characterization of newly emerged V. cholerae O1, Inaba strains isolated from patients with diarrhoea. METHODS: Bacterial characterization was made using polymerase chain reaction, ribotyping, PFGE and RFLP. RESULTS: After its first appearance in July 2004, O1 Inaba became the dominant serotype by March 2005 and totally replaced the former dominant serotype, Ogawa from May 2005. Most of the Inaba isolates belong to a new ribotype RIV. Ogawa and also some Inaba strains isolated during the same period were identified as RIII. Similarly, the majority of the Inaba isolates belong to 'H1' pulsotype and one isolate is type 'H', while the Ogawa isolates were mostly 'H' pulsotype. Presence of CTX prophage was detected in a single site of the chromosome with at least two RS elements. CONCLUSIONS: There has been a switch of dominant serotype from Ogawa to Inaba in the Kolkata region. This is not necessarily due to emergence of a new clone but does serve as an epidemiological marker. Further analysis at the molecular level will be required to define this trend and to monitor future spread to other regions. PMID- 17854904 TI - Electrophysiologic assessment of sciatic nerve regeneration in the rat: surrounding limb muscles feature strongly in recordings from the gastrocnemius muscle. AB - Striking inconsistencies between the results of morphometric and electrophysiologic examinations of the regenerating nerve were observed in a previous study featuring the bridging of a 14 mm gap in the rat sciatic nerve. To shed light on this dichotomy, seven further rats were subjected to permanent sciatic nerve transection and assessed electrophysiologically, histologically and by retrograde axonal tracing at various postoperative intervals (1 h to 8 weeks). The results of the histological examinations and retrograde tracing revealed that in spite of the fact that compound muscle action potentials could be recorded in the gastrocnemius muscle, no reinnervation of the gastrocnemius muscle, either physiological or aberrant, had actually taken place. Furthermore, it was established that the electrical activity recorded in the gastrocnemius muscle after stimulation of the proximal or distal stump is generated by surrounding hind limb muscles unaffected by denervation. These are stimulated either directly, or indirectly due to spreading of the impulse. It is therefore strongly recommended that caution should be exercised when interpreting recordings from the gastrocnemius muscle after stimulation of a regenerating sciatic nerve in laboratory rodents. PMID- 17854905 TI - A modular display system for insect behavioral neuroscience. AB - Flying insects exhibit stunning behavioral repertoires that are largely mediated by the visual control of flight. For this reason, presenting a controlled visual environment to tethered insects has been and continues to be a powerful tool for studying the sensory control of complex behaviors. To create an easily controlled, scalable, and customizable visual stimulus, we have designed a modular system, based on panels composed of an 8 x 8 array of individual LEDs, that may be connected together to 'tile' an experimental environment with controllable displays. The panels have been designed to be extremely bright, with the added flexibility of individual-pixel brightness control, allowing experimentation over a broad range of behaviorally relevant conditions. Patterns to be displayed may be designed using custom software, downloaded to a controller board, and displayed on the individually addressed panels via a rapid communication interface. The panels are controlled by a microprocessor-based display controller which, for most experiments, will not require a computer in the loop, greatly reducing the experimental infrastructure. This technology allows an experimenter to build and program a visual arena with a customized geometry in a matter of hours. To demonstrate the utility of this system, we present results from experiments with tethered Drosophila melanogaster: (1) in a cylindrical arena composed of 44 panels, used to test the contrast dependence of object orientation behavior, and (2) above a 30-panel floor display, used to examine the effects of ground motion on orientation during flight. PMID- 17854906 TI - Postnatal depression and child outcome at 11 years: the importance of accurate diagnosis. AB - BACKGROUND: One in ten women suffers from postnatal depression (PND) and their children have elevated rates of psychopathology. We compared caseness of PND using the Edinburgh Postnatal Depression Scale (EPDS), the most commonly used research tool for the detection of PND, and the Clinical Interview Schedule (CIS) in terms of their relative abilities to identify infants at risk of psychopathology in middle childhood. METHOD: In a prospective longitudinal primary care study, 147 randomly selected women were administered both the CIS and the EPDS at three months postpartum. Childhood psychopathology was identified by face-to-face interview at 11 years. RESULTS: The risk for psychiatric disorder at 11 years was four times greater among children whose mothers were cases of PND on the CIS, compared to children whose mothers were not depressed. Using the EPDS to identify PND, there was no significant difference in the risk for children whose mothers scored above and below a conventional cut-off score. LIMITATIONS: This study was retrospectively designed and was not part of the original study plan. CONCLUSIONS: These data support the evidence that accurate detection of PND is better achieved by face-to-face clinical interview than through the use of the EPDS. They provide novel evidence that a simple diagnostic clinical interview for PND, in contrast to the EPDS, can identify mothers whose children will be at an increased risk of developing psychiatric disorder in later childhood. PMID- 17854907 TI - How best to identify a bipolar-related subtype among major depressive patients without spontaneous hypomania: superiority of age at onset criterion over recurrence and polarity? AB - BACKGROUND: History of high depressive recurrence (without history of mania/hypomania) has been proposed as a mood subtype close to bipolar disorders. Herein we test whether this is the best approach to this question. METHODS: We systematically evaluated consecutive 224 Major Depressive (MDD) and 336 Bipolar II Disorders (BP-II) outpatients in a private practice, by the SCID for DSM-IV (modified for better probing hypomania by Akiskal and Benazzi [Akiskal, H.S., Benazzi, F., 2005. Optimizing the detection of bipolar II disorder in outpatient private practice: toward a systematization of clinical diagnostic wisdom. J. Clin. Psychiatry 66, 914-921]). We conducted univariate and multivariate analyses on such putative bipolar validators as early age at onset of first major depressive episode (before 21 years), high recurrence, family history for bipolar disorders, and depressive mixed states (mixed depression, i.e. depression plus concurrent hypomanic symptoms), in order to identify an MDD subgroup close to BP II. RESULTS: All bipolar validators were independent predictors of BP-II. Early onset was the only variable which identified an MDD subgroup significantly associated with all bipolar validators. This MDD subgroup was similar to BP-II on age at onset and bipolar family history, and had a high frequency of mixed depression. A dose-response relationship was found between number of bipolar validators present in MDD, and bipolar family history loading among MDD relatives. LIMITATIONS: Study limited to outpatients. CONCLUSIONS: From among the bipolar validators, early age at onset of first major depression (<21 years) was superior to high recurrence (>4 depressive episodes) in identifying an MDD subgroup close to BP-II, which might be subsumed under the broad bipolar spectrum. Implications of unipolar-bipolar boundaries and genetic investigations are discussed. PMID- 17854908 TI - Harm avoidance in subjects with obsessive-compulsive disorder and their families. AB - INTRODUCTION: This study investigates the role of harm avoidance (HA) as a possible risk factor in the familiality of obsessive-compulsive disorder (OCD). HA is considered to be a genetically influenced personality trait with an increasingly understood neuroanatomical basis. METHOD: 75 subjects with OCD from hospital sites and a community sample and their 152 first degree relatives and 75 age and sex matched controls with their 143 first degree relatives were evaluated with structured clinical interviews (DSM-IV). HA was assessed with Cloninger's Tridimensional Personality Questionnaire (TPQ). RESULTS: Subjects with OCD had higher scores of HA than controls (p40 when approximately 500 strains from Korea and South America are sequenced. Some of the newly identified alleles cannot be correctly assigned to one of the nine subdivisions based on the proposed diagnostic SNPs. Before SNPs are proposed as characters to define species, it is important to verify their specificity based on a sufficiently large sample and to evaluate the genetic variation present in terms of an independent measure of genetic relationships. Only in such a manner can names that are meaningful in the context of trade and quarantine regulations be developed. PMID- 17854937 TI - Physiological relationship between food preservatives, environmental factors, ochratoxin and otapksPV gene expression by Penicillium verrucosum. AB - There is significant interest in trying to understand the relationship between environmental factors, preservative concentration and expression of genes involved in mycotoxin production. However, little information is available on the link between physiological stress factors and expression of genes responsible for mycotoxin production. This study has examined the effect of interactions between ionic and non-ionic water availability modified with glycerol or NaCl (a(w), 0.98, 0.95 and 0.93) and sub-optimal concentrations of calcium propionate and potassium sorbate (150, 300 ppm) at 25 degrees C on growth, ochratoxin A (OTA) and otapksPV gene expression by the mycotoxigenic species Penicillium verrucosum. Growth was inhibited between 25-35% by the preservatives at each a(w) level. However, OTA production was stimulated by 150 and 300 ppm of both preservatives, especially at 0.95 and 0.93 a(w). If water activity as a single stress factor was changed, a typical OTA production and otapksPV expression profile occurred, indicating that OTA biosynthesis is activated under two conditions, i.e., under optimal growth conditions and under weak stress conditions. Temporal analysis of otapksPV expression showed that there was an optimum after 8-9 days incubation. Statistical analyses indicated good correlation between sub-optimal concentrations of preservatives, intermediate a(w) levels and genotypic and phenotypic gene and toxin production. This is the first time that genotypic information has been linked to phenotypic mycotoxin production in relation to such interacting stress factors. PMID- 17854938 TI - On the design of in situ forming biodegradable parenteral depot systems based on insulin loaded dialkylaminoalkyl-amine-poly(vinyl alcohol)-g-poly(lactide-co glycolide) nanoparticles. AB - The feasibility to generate in situ forming parenteral depot systems from insulin loaded dialkylaminoalkyl-amine-poly(vinyl alcohol)-g-poly(lactide-co-glycolide) nanoparticles, was investigated. Biodegradable nanoparticles formed polymeric semi-solid depots upon injection into isotonic phosphate buffered saline (PBS) with no additional initiators. Nanoparticles (NP) prepared from the different amine-modified polyesters displayed a pronounced positive zeta-potential of >25 mV. Diethylaminopropyl-amine-poly(vinyl alcohol)-g-poly(lactide-co-glycolide) (DEAPA(68)-PVAL-g-PLGA(1:20)), diethylaminoethyl-amine-poly(vinyl alcohol)-g poly(lactide-co-glycolide) (DEAEA(33)-PVAL-g-PLGA(1:20)), and dimethylaminopropyl amine-poly(vinyl alcohol)-g-poly(lactide-co-glycolide) (DMAPA(33)-PVAL-g PLGA(1:20)), formed in situ depots by an ion-mediated aggregation with subsequent fusion of nanoparticles, related to a decreased glass transition temperature in the presence of PBS. Moreover, two factors, namely, polymer and insulin nanocomplex concentration, were evaluated using a response surface design with respect to nanoparticles formation and insulin loading. Nanoparticles and implants were investigated by atomic force microscopy (AFM). The in vitro release from implants loaded with 2% insulin was carried out in a flow trough cell and quantified by high performance liquid chromatography (HPLC). The release showed a triphasic profile with an initial burst, pore diffusion and diffusion from the swollen matrix over more than two weeks. Insulin distribution in the implants during the release was followed by confocal laser scanning microscopy (CLSM). These findings combined with the protection of the model peptide against competitive macromolecules and the possibility to get dry powders by lyophilization make these nanoparticles-based depots suitable candidates for the design of controlled release devices for bioactive macromolecules. PMID- 17854939 TI - Optimisation of intradermal DNA electrotransfer for immunisation. AB - The development of DNA vaccines requires appropriate delivery technologies. Electrotransfer is one of the most efficient methods of non-viral gene transfer. In the present study, intradermal DNA electrotransfer was first optimised. Strong effects of the injection method and the dose of DNA on luciferase expression were demonstrated. Pre-treatments were evaluated to enhance DNA diffusion in the skin but neither hyaluronidase injection nor iontophoresis improved efficiency of intradermal DNA electrotransfer. Then, DNA immunisation with a weakly immunogenic model antigen, luciferase, was investigated. After intradermal injection of the plasmid encoding luciferase, electrotransfer (HV 700 V/cm 100 micros, LV 200 V/cm 400 ms) was required to induce immune response. The response was Th1-shifted compared to immunisation with the luciferase recombinant protein. Finally, DNA electrotransfer in the skin, the muscle or the ear pinna was compared. Muscle DNA electrotransfer resulted in the highest luciferase expression and the best IgG response. Nevertheless electrotransfer into the skin, the muscle and the ear pinna all resulted in IFN-gamma secretion by luciferase-stimulated splenocytes suggesting that an efficient Th1 response was induced in all case. PMID- 17854940 TI - Prevention of tumor recurrence and distant metastasis formation in a breast cancer mouse model by biodegradable implant of 131I-norcholesterol. AB - Brachytherapy has many potential roles in cancer therapy. However, major constraints are associated with placement and removal procedures of the brachytherapy machinery. An attractive approach would be the use of a biodegradable implant loaded with a radioisotope, thus enabling targeted radiotherapy, while reducing the need for surgical procedures for the removal of brachytherapy hardware. In this study, crosslinked chitosan (Ct) hydrogels were prepared and loaded with (131)I-norcholesterol ((131)I-NC). The radioactive hydrogels ((131)I-NC-Ct) were implanted adjacent to 4T1 cell-induced tumors in two different xenograft mice models either as primary therapy or surgical adjuvant therapy of breast cancer. Non-treated mice and mice implanted with naive (non-radioactive) hydrogels served as control groups. In the primary therapy model, the progression rate of the tumor was delayed by two weeks compared with the non-treated and the naive-implant control animals, resulting in a one-week extension in the survival of the treated animals. In the adjuvant therapy model, for the treatment of minimal residual disease, (131)I-NC-Ct implants were able to prevent 69% of tumor recurrence, and to prevent metastatic spread resulting in long-term survival, compared with 0% long-term survival of the non-treated and the naive control groups. Imaging of the hydrogel's in vivo elimination revealed a first order process with a half-life of 14 days. The degradation was caused by oxidation of the Ct as was assessed by in vitro H&E stain. Biodegradable radioactive implants are suggested as a novel platform for the delivery of brachytherapy. This radiotherapy regimen may prevent locoregional recurrence and metastatic spread after tumor resection. PMID- 17854941 TI - Retargeting of adenoviral gene delivery via Herceptin-PEG-adenovirus conjugates to breast cancer cells. AB - Targeted adenoviral gene delivery using human epidermal growth factor receptor 2 (HER2/neu) is one of the promising strategies for enhancing the transduction efficacy of PEGylated adenovirus (PEG-ADV). The viral capsid of adenovirus carrying the green fluorescent protein (GFP) was conjugated with bifunctional polyethylene glycol (PEG). The surface of PEG-ADV was then further conjugated with anti-HER2/neu monoclonal antibody (MAb), Herceptin (Trastuzumab; HER) to grant HER2/neu over-expressed breast cancer cells specific targeting. The PEG-ADV and Herceptin immobilized PEG-ADV (HER-PEG-ADV) extents of retargeting were evaluated, as compared to those of naked ADV. In summary, HER-PEG-ADV exhibited more enhanced level of GFP expression than PEG-ADV did for MDA-MB-435 and MDA-MB 468 cells (a HER2/neu positive cell line), but not for a HER2/neu deficient U251N cells. PEGylated ADV significantly reduced innate immune response likewise, as judged from the amount of interleukin 6 released from macrophage cells. Consequently, this study suggests that HER-PEG-ADV conjugates enable ADV to become more potential therapeutic tools through overcoming the limitation of ADV against immune system and non-specificity. PMID- 17854942 TI - [Effect of thoracic bracing on lung function in children with neuromuscular disease]. AB - Respiratory muscle weakness associated with scoliosis in neuromuscular disease leads to respiratory impairment. Children with scoliosis are usually treated with spinal bracing to delay the progress of disease. We studied the impact of spinal bracing on lung function in these children. METHODS: Retrospective study of patient data from January 1997 to January 2003. Spirometry and measurement of lung volume involved 32 observations, corresponding to 17 children with neuromuscular disease, including 14 with spinal muscular atrophy. Data for children with and without a brace were studied. RESULTS: A total of 72% of the children had severe scoliosis (Cobb score>30 degrees ); 40% wore a Garchois brace. Children without a brace showed a mean vital capacity of 65% of predicted value, with a restrictive syndrome in 44% of observations. Children with a brace showed significantly reduced vital capacity (-4.6%; P<0.001) and forced expiratory volume in 1 s (-4.6%; P=0.002). The reduced vital capacity was lower in children with the Garchois brace: -1% (P=0.02). Severity of scoliosis and measured volumes were not related. CONCLUSION: Spinal bracing in children with neuromusclar disease leads to significant respiratory impairment. Assessment of pulmonary function is necessary when a brace is indicated. The Garchois brace might lead to less impairment of respiratory function. PMID- 17854943 TI - Beta-cell replacement and regeneration: Strategies of cell-based therapy for type 1 diabetes mellitus. AB - Pancreatic islet transplantation has demonstrated that long-term insulin independence may be achieved in patients suffering from diabetes mellitus type 1. However, because of limited availability of islet tissue, new sources of insulin producing cells that are responsive to glucose are required. Development of pancreatic beta-cell lines from rodent or human origin has progressed slowly in recent years. Current experiments for ex vivo expansion of beta cells and in vitro differentiation of embryonic and adult stem cells into insulin producing beta-cell phenotypes led to promising results. Nevertheless, the cells generated to date lack important characteristics of mature beta cells and generally display reduced insulin secretion and loss of proliferative capacity. Therefore, much better understanding of the mechanisms that regulate expansion and differentiation of stem/progenitor cells is necessary. Here, we review recent advances in the identification of potential cellular sources, and the development of strategies to regenerate or fabricate insulin producing and glucose sensing cells that might enable future cell-based therapies of diabetes mellitus type 1. PMID- 17854944 TI - Pharmacological treatment of hepatorenal syndrome: a note of optimism. PMID- 17854945 TI - Positive serum hepatitis B e antigen is associated with higher risk of early recurrence and poorer survival in patients after curative resection of hepatitis B-related hepatocellular carcinoma. AB - BACKGROUND/AIMS: To study the impact of hepatitis B e antigen on tumor recurrence and patients' survival after curative resection of hepatocellular carcinoma. METHODS: Two hundred and three patients with small hepatocellular carcinomas (3cm) who had undergone curative resection were divided into HBeAg-positive group and HBeAg-negative group. Clinicopathological factors and postoperative outcomes were compared between groups, and risk factors for survival and recurrence were studied. RESULTS: The median follow-up time was 32.9months. Patients with negative HBeAg had higher 5-year overall survival rates (76% vs 53.9%, hazards ratio (HR): 2.363, 95% CI: 1.335-4.181, p=0.002) and 5-year disease-free survival rates (52.9% vs 37.4%, HR: 1.603, 95% CI: 1.00-2.561, p=0.046). There was no significant difference in operative morbidity and tumor factors between the two groups, but younger age, higher serum alanine aminotransferase levels, and more macronodular cirrhosis were found in the HBeAg-positive group. Multivariate analysis revealed that age >50years, HBeAg positivity and macronodular cirrhosis were independent factors for overall survival, and HBeAg positivity and multiple tumor nodules were independent factors for disease-free survival. Positive serum HBeAg was associated with a higher risk of early recurrence (within 1year). CONCLUSIONS: HBeAg is associated with a higher risk of early recurrence and poorer survival in patients after curative resection of small HCC. PMID- 17854946 TI - Prescribing in maternity care in Russia: the legacy of Soviet medicine. AB - Remarkably, there has been very little detailed research on clinical practice in Russia and its neighbours in what was the USSR, even though it is known that the USSR was isolated from many international developments, in particular evidence based medicine. In this study we examine obstetric practice, an area of practice where there is an extensive body of evidence on the appropriateness of many interventions. The study is undertaken in Tula, a region 200 km south of Moscow. Building on earlier detailed analyses of data from the facilities in the region, it reports a series of structured interviews with 52 obstetricians from all 19 facilities in the region, designed to identify patterns of prescribing, supplemented by 36 more detailed re-interviews to explore reasons for the differing practices. The study demonstrates a widespread divergence from internationally accepted practice. Maternity care is extremely medicalised but many non-evidence based medicines are used. Some are heavily marketed by large pharmaceutical companies, some were widely used during the Soviet period but never evaluated, and a few are not known to be used anywhere else in the world. For several conditions, the most widely used drugs are clearly inferior to alternative products and some are used for indications quite different from those in other countries. This study contributes to the growing evidence that much of the care provided in Russian maternity units is ineffective or potentially dangerous but also begins to offer some explanations for why this is, including a lack of access to information and a lack of awareness of the concept of evidence based practice. PMID- 17854947 TI - Arthemis: annotation software in an integrated capturing and analysis system for colonoscopy. AB - Colonoscopy is an endoscopic technique that allows physicians to inspect the inside of the human colon. During a colonoscopic procedure, a tiny video camera at the tip of the endoscope generates a video signal of the internal mucosa of the colon. In current practice, the entire colonoscopic procedure is not routinely captured. Software tools providing easy access to important contents of videos that are digitally captured during colonoscopy are not available. Hence, it is very time consuming to review an entire video, locate important contents, annotate them, and extract the annotated contents for research, teaching, and training purposes. Arthemis, a software application, was developed to facilitate this process. For convenient data sharing, Arthemis allows annotation according to the European Gastrointestinal Society for Endoscopy (ESGE) Minimal Standard Terminology (MST), an internationally accepted standard for digestive endoscopy. Arthemis is part of our integrated capturing and content analysis system for colonoscopy called Endoscopic Multimedia Information System (EMIS). This paper presents Arthemis as a component of EMIS, the design and implementation of Arthemis, and key lessons learned from the development process. PMID- 17854949 TI - Decreased expression of the SIN3A gene, a candidate tumor suppressor located at the prevalent allelic loss region 15q23 in non-small cell lung cancer. AB - To identify the tumor suppressor genes (TSG) associated with non-small cell lung cancers (NSCLC), we performed the loss of heterozygosity (LOH) analysis in NSCLC samples from 66 patients. We focused on the novel hot spot region on 15q14-24 with eight polymorphic microsatellite markers. Frequent allelic loss was detected in 33 of 48 informative cases (69%) at D15S984 on 15q23. We defined the fine map on the region and identified the SIN3A gene as a candidate TSG. The SIN3A gene product is a component of the histone deacetylase (HDAC) complex and plays essential roles in early embryonic development and the proliferation and survival of a variety of cells through the repression of diverse signaling pathways. Our expression analysis revealed more frequent down-regulation of the SIN3A mRNA in 19 of 31 cases (61%) of NSCLCs in comparison to those of other flanking genes (16 42%), albeit the correlation of the decreased expression with the LOH did not attain statistic significance. These results suggest that the attenuated function of SIN3A due to a decreased level of expression may result in epigenetic de regulation of growth-related genes through histone acetylation, which leads to the tumorigenesis of lung cancer cells. To our knowledge, this is the first evidence of the down-regulation of the SIN3A gene in human cancer. PMID- 17854950 TI - Transport of Escherichia coli and solutes during waste water infiltration in an urban alluvial aquifer. AB - Recharge of waste water in an unconsolidated poorly sorted alluvial aquifer is a complex process, both physically and hydrochemically. The aim of this paper is to analyse and conceptualise vertical transport mechanisms taking place in an urban area of extensive wastewater infiltration by analysing and combining the water balance, the microbial (Escherichia coli) mass balance, and the mass balance for dissolved solutes. For this, data on sediment characteristics (grain size, organic carbon, reactive iron, and calcite), groundwater levels, and concentrations of E. coli in groundwater and waste water were collected. In the laboratory, data on E. coli decay rate coefficients, and on bacteria retention characteristics of the sediment were collected via column experiments. The results indicated that shallow groundwater, at depths of 50 m below the surface, was contaminated with E. coli concentrations as high as 10(6) CFU/100 mL. In general, E. coli concentrations decreased only 3 log units from the point of infiltration to shallow groundwater. Concentrations were lower at greater depths in the aquifer. In laboratory columns of disturbed sediments, bacteria removal was 2-5 log units/0.5 cm column sediment. Because of the relatively high E. coli concentrations in the shallow aquifer, transport had likely taken place via a connected network of pores with a diameter large enough to allow bacterial transport instead of via the sediment matrix, which was inaccessible for bacteria, as was clear from the column experiments. The decay rate coefficient was determined from laboratory microcosms to be 0.15 d(-1). Assuming that decay in the aquifer was similar to decay in the laboratory, then the pore water flow velocity between the point of infiltration and shallow groundwater, coinciding with a concentration decrease of 3 log units, was 0.38 m/d, and therefore, transport in this connected network of pores was fast. According to the water balance of the alluvial aquifer, determined from transient groundwater modelling, groundwater flow in the aquifer was mainly in vertical downward direction, and therefore, the mass balance for dissolved solutes was simulated using a 1D transport model of a 200 m column of the Quaternary Alluvium aquifer. The model, constructed with PHREEQC, included dual porosity, and was able to adequately simulate removal of E. coli, cation-exchange, and nitrification. The added value of the use of E. coli in this study was the recognition of relatively fast transport velocities occurring in the aquifer, and the necessity to use the dual porosity concept to investigate vertical transport mechanisms. Therefore, in general and if possible, microbial mass balances should be considered more systematically as an integral part of transport studies. PMID- 17854951 TI - Contaminant degradation in physically and chemically heterogeneous aquifers. AB - This paper examines the importance of the correlation between hydraulic conductivity (K) and degradation rate constant (k) during the transport of reactive contaminants in heterogeneous aquifers. We simulated reactive transport in an ensemble of two-dimensional heterogeneous aquifers. Two sets of transport simulations were conducted: one in which a perfect positive correlation was assumed between ln(K) and ln(k), and one in which a perfect negative correlation was assumed. We found that the sign of the correlation has important consequences for the contaminant transport. Qualitatively, a negative correlation leads to significantly more pronounced "fingering" of the contaminant plume than does a positive correlation, with potentially important consequences for downgradient receptors. Quantitatively, the expected behavior (as quantified by the contaminant mass remaining in the aquifer) is statistically different between the positive and negative cases: on average, more contaminant mass persists when K and k are negatively correlated. Also, the negative correlation leads to more variability between realizations of the ensemble, whereas a positive correlation induces relatively little variability between realizations. We discuss the implications of these findings for the management of contaminated aquifers. PMID- 17854952 TI - Synthesis and antioxidant activity evaluation of new hexahydropyrimido[5,4 c]quinoline-2,5-diones and 2-thioxohexahydropyrimido[5,4-c]quinoline-5-ones obtained by Biginelli reaction in two steps. AB - New hexahydropyrimido[5,4-c]quinoline-2,5-diones and 2 thioxohexahydropyrimido[5,4-c]quinoline-5-ones were prepared in two steps from ethyl 4-phenyl-6-methyl-2-oxo tetrahydropyrimidine-5-carboxylates or 4-phenyl-6 methyl-2-thioxotetrahydropyrimidine-5-carboxylates, previously prepared by Biginelli reaction using appropriate aldehyde, urea derivatives and ethyl acetoacetate. Their antioxidant properties were evaluated by two methods: scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and scavenging effect on hydroxyl radicals. The results show that the compounds containing thiourea moiety have better activity. PMID- 17854953 TI - Substantive theory on commitment to nurse teacherhood. AB - Nurse teacherhood is usually examined from the perspectives of nurse teachers' tasks, roles, skills and managing. The purpose of this study was to discuss how nurse teachers themselves describe their teacherhood. The purpose was also to generate a substantive theory of nurse teacherhood, its development, changes and manifestation. Nurse teachers from different polytechnics (today called universities of applied sciences) in Finland (N=34) were interviewed using a semi structured interview. The data were analysed by employing the grounded theory method. Nurse teacherhood was found to be a dynamic process influenced by processes of change in the organisation, the operating culture of the health care working community, nurse teachers' professional self-esteem, the focus of nurse teachers' competence, their relationship with students, the future of their profession and requirements for staying in the profession. Commitment emerged as the core feature of nurse teacherhood. It was possible to distinguish eight types of commitment: (1) searching for new content in one's position, (2) being adapted to one's position, (3) trying to advance in one's position, (4) having found one's position, (5) searching for one's position, (6) withdrawing from one's position, (7) being satisfied with one's position and (8) being uncertain about one's position. PMID- 17854954 TI - Higher total ghrelin levels are associated with higher insulin-mediated glucose disposal in non-diabetic maintenance hemodialysis patients. AB - BACKGROUND & AIMS: Insulin resistance is common in maintenance hemodialysis (MHD) and it can contribute to exceedingly high mortality in MHD patients. Ghrelin is a gastric hormone whose total plasma concentration is increased in MHD. Emerging data suggest a potential role of ghrelin to modulate intermediate metabolism but the metabolic impact of ghrelin in chronic kidney disease is unknown. The current study aimed at assessing the potential relationships between ghrelin and insulin sensitivity in MHD. METHODS: Total (T-Ghr) and acylated (A-Ghr) ghrelin as well as insulin-mediated glucose disposal [(M): hyperinsulinemic-euglycemic clamp] were measured in non-diabetic non-obese ambulatory MHD patients (n=19, 16 Males). C-reactive protein (CRP) was also measured since systemic inflammation is associated with insulin resistance in non-renal patients and inflammation is negatively modulated by ghrelin in experimental models. RESULTS: Compared to control subjects (C: n=9, 7 Males), MHD had similar body fat and resting energy expenditure but reduced M and increased CRP (P<0.05). MHD also had higher T (P<0.05) but not A-Ghr. M was associated positively with T-Ghr and negatively with CRP in linear regression analysis in MHD. In stepwise multiple regression analysis only T-Ghr remained associated with M (P<0.05) in a model including A Ghr and CRP. CONCLUSIONS: Insulin sensitivity is associated negatively with systemic inflammation and positively with total plasma ghrelin in non-diabetic MHD patients. Based on available knowledge these results suggest a potential novel role of ghrelin in preserving insulin sensitivity in MHD. PMID- 17854956 TI - Vaccine preventable diseases in indigenous populations - International perspectives. Satellite Symposium of the 5th International Symposium on Pneumococci and Pneumococcal Diseases, April 2006, Alice Springs, Australia. PMID- 17854955 TI - Live attenuated Listeria monocytogenes expressing HIV Gag: immunogenicity in rhesus monkeys. AB - Induction of strong cellular immunity will be important for AIDS vaccine candidates. Natural infection with wild-type Listeria monocytogenes (Lm), an orally transmitted organism, is known to generate strong cellular immunity, thus raising the possibility that live attenuated Lm could serve as a vaccine vector. We sought to examine the potential of live attenuated Lm to induce cellular immune responses to HIV Gag. Rhesus macaques were immunized with Lmdd-gag that expresses HIV gag and lacks two genes in the D-alanine (D-ala) synthesis pathway. Without this key component of the bacterial cell wall, vaccine vector replication critically depends on exogenous D-ala. Lmdd-gag was given to animals either solely orally or by oral priming followed by intramuscular (i.m.) boosting; D-ala was co-administered with all vaccinations. Lmdd-gag and D-ala were well tolerated. Oral priming/oral boosting induced Gag-specific cellular immune responses, whereas oral priming/i.m. boosting induced systemic as well as mucosal anti-Gag antibodies. These results suggest that the route of vaccination may bias anti-Gag immune responses either towards T-helper type 1 (Th1) or Th2 responses; overall, our data show that live attenuated, recombinant Lmdd-gag is safe and immunogenic in primates. PMID- 17854957 TI - Specificity of recumbent cycling as a training modality for the functional movements; sit-to-stand and step-up. AB - BACKGROUND: The principle of specificity in muscle training requires the training mode to reflect the desired outcome. The observed similarity of lower limb movements during recumbent cycling to the functional movements sit-to-stand and step-up presents the possibility of using recumbent cycling in a rehabilitation context. This may reduce the need to practice the actual task which in some, less able, patients may be labour intensive and patient fatiguing. To date no studies have compared recumbent cycling to these functional movements. This study therefore aimed to compare the lower limb kinematics and muscle activity between recumbent cycling and both sit-to-stand and step-up movements. METHODS: Electromyographic and kinematic signals from 12 young (mean age 42.1 years) healthy participants were collected during the performance of three activities: (1) cycling at 60 rpm, (2) sit-to-stand and (3) a single step-up. Only the extension phase of each movement was compared. FINDINGS: Although the results demonstrated differences in joint movement and muscle activation, e.g., greater gastrocnemius activity during recumbent cycling (P<0.00), knee range of motion and average root mean square activity for rectus femoris, biceps femoris and the sum of the average activity for five muscles recorded showed no difference (P>0.05) suggesting that there was sufficient agreement to support the use of recumbent cycling as a specific training modality for the sit-to-stand and step up movements. This finding may have positive implications for the rehabilitation of a wide range of patients in the early stages of rehabilitation. PMID- 17854958 TI - Three-dimensional stiffness in a thoracolumbar en-bloc spondylectomy model: a biomechanical in vitro study. AB - BACKGROUND: In selected cases, en-bloc spondylectomy is the only option to reach wide resection margins for patients with malignant tumours of the thoracolumbar spine. These patients must be also provided a secure initial stabilization of the spine and this is the role of vertebral body replacements employed with posterior fixation systems. The aim of this study was to determine the postimplantation stiffness of a connected vertebral body replacement pedicle screw system in different implantation scenarios following an en-bloc spondylectomy. Reconstruction was varied by posterior fixation lengths and axial compression forces during implantation. METHODS: Three-dimensional stiffness was assessed in 6 fresh frozen human spinal specimens (Th11-L3) using a six degree of freedom spine simulator. Following en-bloc spondylectomy reconstruction was performed using a carbon composite fibre vertebral body replacement connected to a posterior fixation system by two artificial pedicles. The spines were loaded with pure moments (7.5Nm) in the three main motion planes. The intersegmental rotations were measured between Th12 and L2. FINDINGS: Reconstructions using long posterior fixation modes demonstrated significant (P<0.05) higher stiffness compared to short posterior fixations in all motion planes. In axial rotation short posterior fixation modes failed to reach the values of the intact state. Neither high nor low axial compression force during implantation showed a significant impact on postfusional stiffness. INTERPRETATION: In this biomechanical model, the employed system should be implanted with a posterior fixation of two adjacent segments to the lesion in order to achieve a secure stabilization of the treated segment. PMID- 17854959 TI - Bioavailable DDT residues in sediments: laboratory assessment of ageing effects using semi-permeable membrane devices. AB - We describe the reduction in bioavailability of DDT in contaminated soil after it was incubated as sediment for 365 d. Bioavailability was assessed using semi permeable membranes. Contaminated soils from three cattle dip sites, one spiked paired uncontaminated site, and one spiked OECD standard soil were studied. Sandy soil with residues of 1880 mg/kg summation operator DDT incurred since 1962, initially had 4.6% of summation operator DDT available, reducing to 0.6% following 365 d. Clay soil (1108 mg summation operator DDT/kg) had 4.1% initially available, reducing to 0.3% after 365 d. Freshly spiked soils had a greater amount of DDT initially available (10.9%), but this reduced to 1.5% by the end of the incubation. Of the DDT congeners, both o,p'-DDD and p,p'-DDD were most bioavailable in the soils, but also had the most significant decrease following incubation. PMID- 17854960 TI - Mass fluxes and spatial trends of xenobiotics in the waters of the city of Halle, Germany. AB - The behaviour and the effects of xenobiotics including pharmaceuticals and fragrances in the environment are widely unknown. In order to improve our knowledge, field investigations and modelling approaches for the entire area of the city of Halle/Saale, Germany, were performed. The distribution of the concentration values and mass fluxes are exemplified using indicators such as Bisphenol A, t-Nonylphenol, Carbamacepine, Galaxolide, Tonalide, Gadolinium and isotopes. Concentrations at a magnitude of ng/L to microg/L were found ubiquitously in the ground and surface waters. Using the concentration values, the impact of the city concerning the indicators was not always evident. Only the assessment of the mass fluxes shows significant urban impacts along the city passage. The calculation of the mass fluxes shows increasing values for all investigated xenobiotics during the city passage; only Bisphenol A stagnates. A balance model of water and indicator mass fluxes was built up for the entire city area. PMID- 17854961 TI - Monitoring contaminants from oil production at sea by measuring gill EROD activity in Atlantic cod (Gadus morhua). AB - An ex vivo gill EROD assay was applied in Atlantic cod (Gadus morhua) as a biomarker for waterborne CYP1A-inducing compounds derived from oil production at sea. Exposure to nominal concentrations of 1 ppm or 10 ppm North Sea crude oil in a static water system for 24 h caused a concentration-dependent gill EROD induction. Further, exposure of cod for 14 days to environmentally relevant concentrations of produced water (PW, diluted 1:200 or 1:1000) from a platform in the North Sea using a flow-through system resulted in a concentration-dependent induction of gill EROD. Crude oil (0.2 ppm) from the same oil field also proved to induce EROD. Finally, gill EROD activity in cod caged for 6 weeks at 500-10 000 m from two platforms outside Norway was measured. The activities in these fish were very low and did not differ from those in fish caged at reference sites. PMID- 17854962 TI - Seasonal air-water exchange fluxes of polychlorinated biphenyls in the Hudson River Estuary. AB - Polychlorinated biphenyls (PCBs) were measured in the air and water over the Hudson River Estuary during six intensive field campaigns from December 1999 to April 2001. Over-water gas-phase SigmaPCB concentrations averaged 1100 pg/m3 and varied with temperature. Dissolved-phase SigmaPCB concentrations averaged 1100 pg/L and displayed no seasonal trend. Uncertainty analysis of the results suggests that PCBs with 5 or fewer chlorines exhibited net volatilization. The direction of net air/water exchange could not be determined for PCBs with 6 or more chlorines. Instantaneous net fluxes of SigmaPCBs ranged from +0.2 to +630 ng m(-2) d(-1). Annual fluxes of SigmaPCBs were predicted from modeled gas-phase concentrations, measured dissolved-phase concentrations, daily surface water temperatures and wind speeds. The net volatilization flux was +62 microg m(-2) yr(-1), corresponding to an annual loss of +28 kg/yr of SigmaPCBs from the Hudson River Estuary for the year of 2000. PMID- 17854963 TI - Fathers' role in the etiology, prevention and treatment of child anxiety: a review and new model. AB - Fathers have been neglected in investigations of the development, prevention, and treatment of anxiety and anxiety disorders in children and adolescents. This review provides a historical background of what is known about fathers' roles in the etiology of anxiety problems and provides evidence from bottom-up, top-down, and cross-sectional correlation studies of the connections between fathers' and their children's anxiety. Treatment and prevention programs are discussed in terms of the limited findings regarding fathers' involvement in treatment for children's and adolescents' anxiety problems. Finally, a model is presented to show the unique ways in which mothers and fathers are involved in the development of anxiety disorders in their children. Future directions for research in this area are highlighted. PMID- 17854964 TI - Competent children? Minors' consent to health care treatment and research. AB - This paper concentrates on controversies about children's consent, and reviews how children's changing status as competent decision makers about healthcare and research has gradually gained greater respect. Criteria for competence have moved from age towards individual children's experience and understanding. Uncertain and shifting concepts of competence and its identification with adulthood and childhood are examined, together with levels of decision-making and models for assessing children's competence. Risks and uncertainties, methods of calculating the frequency and severity of risks, the concept of 'therapeutic research' and problems of expanding consent beyond its remit are considered. The paper ends by considering how strengths and limitations in children's status and capacities to consent can be mirrored in researchers' and practitioners' own status and capacities. Examples are drawn from empirical research studies about decision making in healthcare and research involving children in the UK. PMID- 17854965 TI - The role of the bioethicist in family meetings about end of life care. AB - There has been little study of the content of bioethicists' communication during family meeting consultations about end of life care. In the literature, two roles for bioethicists are usually described: the "consultant" role, in which bioethicists define and support ethical principles such as those enshrined in the "rational choice" model; and the "mediator" role, which focuses on the enhancement of communication in order to reduce conflict. In this study, we use observational data to explore how bioethicists support the practice of decision making during family meetings about end of life care. In a study conducted in the Bronx, New York, USA, researchers observed and recorded 24 decision-making meetings between hospital staff and family members of elderly patients identified as being in the last stages of illness, who were unable or unwilling to make the decision for themselves. Bioethics consultants were present during five of those meetings. Although bioethicists referred to the "rational choice" decision-making hierarchy, we did not see the systematic exploration described in the literature. Rather, our data show that bioethicists tended to employ elements of the rational model at particular turning points in the decision-making process in order to achieve pragmatic goals. As mediators, bioethicists worked to create consensus between family and staff and provided invaluable sympathy and comfort to distressed family members. We also found evidence of a context-dependent approach to mediation, with bioethicists' contributions generally supporting staff views about end of life care. Bioethicists' called to consult on family meetings about end of life care do not appear to adhere to a strict interpretation of the official guidelines. In order to negotiate the difficult terrain of end of life decision making, our data show that bioethicists often add a third role, "persuader", to official roles of "consultant" and "mediator". PMID- 17854966 TI - Ethnography/ethics. AB - This paper situates discussion of the ethics of ethnographic research against the background of a theoretical and methodological debate about the relationship between ethics and method, and about the relationships between research methods and their objects. In particular, the paper investigates the implications of folding together the ethical and the empirical in research and argues that this requires the development of new ethico-ethnographic methods for the investigation of ethico-moral objects. The paper falls into three main parts. The first considers calls for what has come to be known as empirical ethics, that is, for a more empirically informed bioethics, by way of an exploration of the integration of ethnographic methods in bioethics, and concludes that approaches which see the ethical and the empirical as 'complementary' do not do justice to the methodological implications of enfolding the ethical and the ethnographic. The second part juxtaposes this with calls for the integration of ethics in ethnography and, similarly, argues that the enfolding of the ethical and the empirical in ethnography calls for the development of new methods. The paper goes on to problematise the 'negotiational' approaches to informed consent preferred by many ethnographers, arguing that the concept of negotiation, rather than offering a solution to the problem of consent, is itself ethically complex and in need of analysis. The paper argues that, in the context of ethnographic research, the possibility of negotiational forms of consent depends upon engagement between researchers and researched, with unavoidably 'ethical' concepts such as 'respect', 'recognition', 'dignity', 'justice' and so on, and that this poses methodological challenges to ethnography. The paper's third section explores the implications of these arguments for research practice, using The Genethics Club as an example. PMID- 17854967 TI - Effect of thought disorders on quality of life in patients with schizophrenia. AB - OBJECTIVE: The aim of the present study was to investigate the impact of thought disorder on quality of life in patients with schizophrenia. METHODS: Seventy two patients with schizophrenia and 46 healthy subjects were included in the study. World Health Organization Quality of Life Instrument Short Forum (WHOQOL-BREF) was given to patients and healthy subjects to assess quality of life. Thought and Language Index (TLI) for thought disorders, Positive and Negative Syndrome Scale (PANNS) for symptom and Calgary Depression Scale (CDS) for depressive symptoms were administered to the patients. RESULTS: The comparison of quality of life between patients and healthy subjects showed a significant difference except environmental domain. There were no significant correlations between thought disorder and quality of life in patients with schizophrenia. CONCLUSION: The present study revealed that quality of life was lower in patients with schizophrenia compared to healthy subjects. There was no relation between thought disorders and quality of life in schizophrenia. Patients with schizophrenia were aware of their quality of life perception. PMID- 17854968 TI - [Why think about tendons allotransplantation in hand surgery in 1989?]. AB - Two cases of a human vascularized allotransplant of a complete digital flexion system are reported with detailed descriptions of the dissection technique and postoperative treatment. Satisfactory functional results open new prospects for this type of transplantation surgery. PMID- 17854969 TI - Effect of resin coating on dentine compared to repeated topical applications of fluoride mouthwash after an abrasion and erosion wear regime. AB - OBJECTIVES: The role of fluoride in preventing erosion and abrasion on dentine remains unclear. The aim of this study was to investigate the effect of repeated applications of a 0.05% fluoride mouthwash and an adhesive on wear of dentine using stainless steel discs reference points and a laser profilometer. METHODS: Small stainless steel discs were bonded to 60 caries free extracted molars which had previously been sectioned horizontally. The teeth were equally divided and subjected to four modalities in an erosion and abrasion laboratory model. Step heights were measured from the metal discs using a non-contacting laser profilometer at 100, 500, 1000, 2500 and 5000 cycles. RESULTS: The results after 5000 cycles showed that dentine coated with a dentine adhesive (0.015 microm, S.D. 0.090) had statistically less wear than fluoride (0.127 microm, S.D. 0.150), abrasion and erosion (0.182 microm, S.D. 0.150) or abrasion only (0.096 microm, S.D. 0.090) (p<0.001). CONCLUSION: In conclusion dentine surfaces coated with a resin-based adhesive provided more protection against erosion and abrasion than a fluoride mouthrinse. There were no statistical differences between the modalities for cycles less than 5000. PMID- 17854970 TI - Telomere dynamics in human cells. AB - Human telomeres are intrinsically dynamic structures, with multiple biological processes operating to generate substantial length heterogeneity. Processes that operate specifically at the terminus, that include the end-replication problem coupled with C-strand resection, result in gradual telomere erosion with ongoing cell division. Rates of telomere erosion can be modulated by cell culture conditions and pleiotropic effects. Other processes, that are not consistent with the end replication problem, generate sporadic large-scale changes in telomere length. These events are detected in normal human cells and tissues; the severely truncated telomeres that result are potentially fusogenic and may lead to the types of genetic rearrangements that typify early-stage neoplasia. The processes that underlie sporadic telomeric deletion are unclear, but may include intra allelic recombination within the T-loop structure, unequal sister chromatid exchange and replication fork stalling. The relative contributions of these processes in the generation of the heterogeneous telomere length profiles observed in human cells are discussed. PMID- 17854971 TI - Telomerase redefined: integrated regulation of hTR and hTERT for telomere maintenance and telomerase activity. AB - Telomerase activity is dependent on the expression of 2 main core component genes, hTERT, which encodes the catalytic component and hTR (also called TERC), which encodes the RNA component. The correlation between telomerase activity and carcinogenesis has made this molecule of great interest in cancer research, however in order to fully understand the regulation of telomerase the mechanisms controlling both telomerase genes need to be studied. Some of these mechanisms of regulation have begun to emerge, however many more remain to be deciphered. For many years hTERT has been regarded as the limiting component of telomerase and much of the research in this field has focussed on its regulation, however it was clear from an early stage that hTR expression was also tightly regulated in normal cells and disease. More recently evidence from biochemistry, promoter studies and mouse models has been steadily increasing for a role for hTR as a limiting and essential component for telomerase activity and telomere maintenance. Perhaps the time has come to redefine our view of telomerase regulation. Knowledge of the mechanisms controlling both telomerase genes in normal systems and cancer may aid our understanding of the role of telomerase in carcinogenesis or highlight potential areas for therapeutic intervention. Here we review the essential requirement of hTR for telomere maintenance and telomerase activity in normal tissues and disease and focus on recent advances in our understanding of hTR regulation in relation to hTERT. PMID- 17854972 TI - Assessment of BLS skills: optimizing use of instructor and manikin measures. AB - BACKGROUND: The primary objective of layperson CPR training is to ensure that learners achieve minimal competence to provide aid that improves the odds of survival of victims of out-of-hospital sudden cardiac arrest. During CPR courses, pronouncement of a learner's competence typically depends entirely on judgments made by an instructor; yet previous research strongly suggests that these judgments - particularly of chest compressions - are not sufficiently precise or accurate to ensure valid assessments. Comparisons of instructors' subjective assessments with objective data from recording manikins provide one means of understanding the magnitude and type of instructor errors in assessment. METHOD: Eight hundred and twenty-six laypersons between 40 and 70 years old participated in CPR training. Performance of five discrete skills was tested in a scenario format immediately afterward: assessing responsiveness, calling the emergency telephone number 911, delivering ventilations of adequate volume, demonstrating correct hand placement for compressions, and delivering compressions with adequate depth. Thirteen AHA-certified instructors assessed these five skills and rendered a global performance rating; sensored Resusci Anne manikins with SkillReporting software recorded ventilation and compression data. RESULTS: Instructors' ratings of the ventilation skills were highly accurate; ratings of compressions were correct about 83% of the time; yet inadequate compression depth was rated adequate 55% of the time, and incorrect hand placement was rated adequate 49% of the time. CONCLUSION: Instructors' judgments alone are not sufficient to determine learners' competence in performing compressions. Assessment, technology, and guidelines must be better aligned so that learners can receive accurate feedback. PMID- 17854973 TI - Introduction: special issue on the economics of invasive species management. PMID- 17854974 TI - From subsistence farming towards a multifunctional agriculture: sustainability in the Chinese rural reality. AB - The rural economic situation in China-with a living standard mostly at subsistence level-lags far behind the prosperous development in the cities and coastal areas. To balance this disequilibrium, comprehensive concepts and endeavors are necessary keeping in view all-not just economic-interests and needs that contribute to lively rural identities. In this context the role of agriculture, where still 50% of the Chinese population are working, will be newly defined, and sustainability concepts can help to find a readjusted position within the Chinese economy focusing on environmental health and food safety as main targets of political and other supporting measures. Within the SUCCESS project, a Concept of Sustainable Agriculture was developed and it drafts one conceivable relation between the exposure to natural resources and economy and tries to find new answers to the broad range of rural challenges in China. It is a qualitative model and, therefore, not always fully applicable, but in the concrete situation of villages, it shows possible directions of sustainability oriented development by considering the typical local potentials. In the Chinese context that means identifying the different functions of agriculture-the well known and the hidden-to make them explicit for the Chinese public and therewith to give them new significance. The article is based on a 3-years study within the EU-China Project SUCCESS with field research in four Chinese rural communities. It analyzes the agricultural sustainability potential of these selected villages against the background of massive structural changes within the next 20 years in rural China. Starting from the current agricultural reality, based on a qualitative analysis of the actual situation, local potentials and needs towards sustainable production and marketing are identified, and possible functions of the Chinese agriculture are formulated for the future. PMID- 17854975 TI - Generating sustainable towns from Chinese villages: a system modeling approach. AB - The great majority of China's developing towns will be extensions of already existing villages. With the prospect of hundreds of millions of Chinese farmers projected to leave their villages to become industrial workers in new and expanded towns within the next few years, new challenges will be faced. As expansion and modernization progress, this development moves from the traditional village model that operates not far from resource sustainability to increasingly unsustainable patterns of commerce, urban development, and modern life. With such an unprecedented mass migration and transformation, how can Chinese culture survive? What is to become of the existing million plus agricultural villages? How can these massively unsustainable new industrial towns survive? In the European Commission sponsored research program SUCCESS, researchers worked from the scale of the Chinese village to find viable answers to these questions. To address these issues, the Center for Sustainable Cities, one of the SUCCESS teams, studied the metabolism of several small villages. In these studies, system dynamics models of a village's metabolism were created and then modified so that inherently unsustainable means were eliminated from the model (fossil fuels, harmful agricultural chemicals, etc.) and replaced by sustainability-oriented means. Small Chinese farming villages are unlikely to survive in anything like their present form or scale, not least because they are too small to provide the range of life opportunities to which the young generation of educated Chinese aspires. As a response to this realization as well as to the many other threats to the Chinese village and its rural way of life, it was proposed that one viable path into the future would be to enlarge the villages to become full service towns with sufficient diversity of opportunity to be able to attract and keep many of the best and brightest young people who are now migrating to the larger cities. Starting with the village in its sustainability-oriented model form, the village model would be enlarged both quantitatively and qualitatively through many trial iterations. A research program is described whereby an operational definition of the sustainable city is developed as a means of creating these enlarged models through citizen participation assisted by outside experts using software under development called the Sustainability Engine to guide the process and provide feedback as to the consequences of various proposals that are brought to the table. As this process is continued, the village would be incrementally enlarged and made more diverse and more complex through a variety of scenarios until it would emerge as a modern, sustainable town or city. In this way, through a participatory, balance-seeking civil society process involving villagers and scientists in what the Center for Sustainable Cities calls the Sustainable City Game, the villages can become the DNA for generating future sustainable Chinese towns and cities. As an extension of this discussion, a new urban model, the Sustainable City-as-a-Hill, is presented that responds to both the qualities of the traditional Chinese village as well as to the modern demands of industrial and post-industrial economies and, in particular, to the need for sustainable urban patterns. In addition a new concept, the Sustainable Area Budget (SAB) is introduced which definitively creates the boundary condition for both modeling the sustainable city and presenting the quest for the sustainable city-region as a coherent, scientific design process. PMID- 17854976 TI - Analytic hierarchy process helps select site for limestone quarry expansion in Barbados. AB - Site selection is a key activity for quarry expansion to support cement production, and is governed by factors such as resource availability, logistics, costs, and socio-economic-environmental factors. Adequate consideration of all the factors facilitates both industrial productivity and sustainable economic growth. This study illustrates the site selection process that was undertaken for the expansion of limestone quarry operations to support cement production in Barbados. First, alternate sites with adequate resources to support a 25-year development horizon were identified. Second, technical and socio-economic environmental factors were then identified. Third, a database was developed for each site with respect to each factor. Fourth, a hierarchical model in analytic hierarchy process (AHP) framework was then developed. Fifth, the relative ranking of the alternate sites was then derived through pair wise comparison in all the levels and through subsequent synthesizing of the results across the hierarchy through computer software (Expert Choice). The study reveals that an integrated framework using the AHP can help select a site for the quarry expansion project in Barbados. PMID- 17854977 TI - The distance between state and rural society in the PRC. Reading document no 1 (February 2004). AB - While the People's Republic of China appears on a daily basis in all of the important newspapers around the world with its enormous successes in modernizing its economy, life in the Chinese countryside usually does not attract international attention. However, we know from a wide range of reports that the situation in the Chinese countryside is getting more and more complicated with local corruption, pollution and poverty growing in most parts of the country. The Chinese language press reports on a growing number of local uprisings in remote areas. While some analysts regard the situation in the countryside as a potential threat to the ongoing peaceful process of economic reform in China, China seems to be well prepared to cope with this change and the state is comparatively flexible in dealing with unrest among the rural population. So far the system itself has not been challenged by peasant discontent. This article introduces the idea that the distance between state and rural society is the basis of this flexibility. It will analyze a major policy document issued by the state and party leadership in order to show how state and rural society interact on the basis of a still insurmountable distance between state and rural society. PMID- 17854979 TI - In vitro evaluation of dual mode ultrasonic thrombolysis method for transcranial application with an occlusive thrombosis model. AB - A recent clinical trial of transcranial low-frequency ultrasound-mediated tPA thrombolysis (LFUT) showed cerebral hemorrhages associated with high spatial peak pulse average intensity (I(SPPA)), wide beam and long pulse duration. We developed an alternative approach to LFUT wherein diagnostic power M-mode Doppler (PMD) ultrasound is combined with LFUT, with a goal of increased safety. The effectiveness of such a dual mode ultrasonic thrombolysis (DMUT) was explored in vitro. The DMUT system emitted PMD (2 MHz) and LFUT (550 kHz) beams in alternating fashion from a small 12 mm diameter probe. The LFUT had a low I(SPPA) (2 W/cm(2)) and a short pulse duration (55 micros). Occlusive clots made in plastic tips from bovine plasma and thrombin were placed in flow models pressurized to 800 mH(2)O, with 600 IU/mL monteplase injected upstream. Recanalization times were then compared among three groups: the control (monteplase alone), PMD (monteplase + PMD) and DMUT (monteplase + PMD + LFUT). The capability of the DMUT device to monitor recanalization was demonstrated by observing with Doppler the degree of flow of a blood-mimicking fluid in the vicinity of the clot. Recanalization times were 37.9 +/- 22.9, 38.9 +/- 12.4 and 18.5 +/- 8.0 min, respectively, for the control, PMD and DMUT. There were significant differences between DMUT and the control (p = 0.0004) and between DMUT and PMD (p = 0.0004). Recanalization flows were clearly detected. It is anticipated that this DMUT method presents a safer and more efficient approach than normal LFUT. PMID- 17854980 TI - Real-time myocardial contrast echocardiography for assessing perfusion and function in healthy and infarcted wistar rats. AB - Real-time myocardial contrast echocardiography (MCE) is a noninvasive perfusion imaging method, whereas technical and resolution problems impair its application in small animals. Hence, we investigated the feasibility of MCE in experimental cardiovascular set-ups involving healthy and infarcted myocardium in rats. Twenty five male Wistar rats were examined under volatile anesthesia (2.5% isoflurane) with high-resolution conventional 2-D echocardiography (2DE) and real-time MCE (Sonos 7,500 with 15MHz-transducer, Philips Medical Systems, Andover, MA, USA) in short-axis view. Contrast agent (SonoVue, Bracco, Milan, Italy) was infused as a bolus into a sublingual vein. Background-subtracted contrast signal intensity (SI) was measured off-line in six end-systolic segments and fitted to an exponential curve (gamma variate). Derived peak SI was subsequently calculated and compared with wall motion and common functional measured quantities (left ventricular end-diastolic diameter [LVEDD], area shortening [AS]). Recordings were performed before and 14 days after left anterior descending (LAD) ligature. Infarction induced anterior wall motion abnormalities (WMA) in all animals (16 akinetic, 9 hypokinetic), increased LVEDD (9.1 +/- 0.6 vs. 7.9 +/- 0.6 mm, p < 0.001), reduced AS (36.1 +/- 10.0 vs. 59.5 +/- 4.1%, p < 0.001) and reduced anterior segmental SI (0.4 +/- 0.4 dB akinetic / 1.7 +/- 1.7 dB hypokinetic vs. 15.8 +/- 10.9 dB preinfarct, p < 0.001 / p < 0.001). Segmental SI in normokinetic segments remained unchanged. Area at risk (perfusion defect) correlated well with WMA (r = 0.838). These data confirmed high-resolution real-time MCE as a rational tool for assessing myocardial perfusion of Wistar rats. It may therefore be a useful diagnostic tool for in-vivo cardiovascular research in small animals. PMID- 17854981 TI - Diagnostic transcranial ultrasound perfusion-imaging at 2.5 MHz does not affect the blood-brain barrier. AB - The purpose was to assess whether standard ultrasound (US) perfusion-imaging by means of contrast-enhanced transcranial color-coded sonography (TCCS) affects the blood-brain barrier (BBB) in patients with small-vessel disease (SVD). One week after a screening MRI to exclude a preexisting BBB disruption, unilateral TCCS phase inversion harmonic imaging (PIHI) was performed in an axial diencephalic plane after intravenous bolus application of 2.5 mL SonoVue (IGEA, Bracco, Italy). Magnetic resonance imaging (MRI) was performed immediately after US. In five patients, PIHI was performed applying a mean mechanical index (MI) of 0.7 +/ 0.1 for a time period of 2.5 min. MRI was started 12 +/- 2 min after US contrast injection. Comparisons of initial and post-US MRI by four blinded readers did not show any signs of BBB disruption. It is concluded that standard contrast-enhanced US perfusion imaging in patients with SVD did not lead to MRI-detectable BBB changes. This gives further evidence for safety of diagnostic US. Future investigations with larger sample sizes and higher-field MRI might give further insights into potential bioeffects of diagnostic, as well as therapeutic, contrast-enhanced transcranial US. PMID- 17854982 TI - The prognostic value of early transcranial Doppler ultrasound following cardiopulmonary resuscitation. PMID- 17854983 TI - Changes in circulating immunosuppressive cytokine levels of cancer patients after high intensity focused ultrasound treatment. AB - Immunosuppression in a patient with malignant tumor is a major obstacle in cancer treatment. In this study, we investigated changes in the circulating level of all measured immunosuppressive cytokines in patients with malignancy before and after high intensity focused ultrasound (HIFU) treatment. Fifteen patients with solid malignancy were enrolled in this study and an enzyme-linked immunoabsorbent assay (ELISA) method was used to measure serum level of vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), transforming growth factor-beta2 (TGF-beta2), interleukin 6 (IL-6) and interleukin 10 (IL-10), respectively before and 1 wk after HIFU treatment. Among them, seven patients had distant metastasis and the remaining eight had no metastasis. All patients received one-session HIFU treatment for primary cancer, including complete ablation in eight patients without metastasis, and partial ablation in seven patients with metastases. The results showed that serum immunosuppressive cytokine levels decreased after HIFU treatment, and there were significant decreases of VEGF, TGF-beta1, and TGF-beta2 before and after HIFU treatment. Compared with the values in the metastatic patients, serum levels of immunosuppressive cytokines were significantly lower in the nonmetastatic patients after HIFU treatment. It is concluded that HIFU can decrease tumor secreted immunosuppressive cytokine production in addition to its direct tumor destruction. This change may lessen tumor-induced immunosuppression and renew antitumor immunity after HIFU in cancer patients. PMID- 17854985 TI - Repeated botulinum toxin injections: a new answer for further questions. PMID- 17854984 TI - Quantification of transmural gradient of blood flow in myocardial ischemia with real-time myocardial contrast echocardiography and dipyridamole stress test. AB - Transmural redistribution of myocardial blood flow (MBF) is the earliest sign of myocardial ischemia. We aimed to evaluate the ability of real-time myocardial contrast echocardiography (MCE) combined with dipyridamole stress to quantify the transmural gradient of MBF during graded coronary stenosis. Real-time MCE was performed in 14 open-chest dogs at seven experimental stages: baseline; hyperemia induced by 6-min infusion of dipyridamole; 50%, 75% and 90% reduction of hyperemic flow after constriction in each stage for 10 min; reperfusion for 10 min; and subtotal occlusion of the left anterior descending coronary artery (LAD) for 90 min. We obtained MCE perfusion parameters from subendocardial (A-endo, beta-endo and A x beta-endo) and subepicardial (A-epi, beta-epi and A x beta-epi) layers of the ventricular septum and calculated their transmural gradients (A EER, beta-EER and A x beta-EER) and systolic wall thickening (SWT). The sensitivity and specificity of each parameter for predicting 75% reduction of hyperemic flow, which was defined as mild myocardial ischemia, were derived by receiver operating characteristic (ROC) curve analysis. No transmural gradients were found at baseline; during maximal hyperemia and 50% reduction of hyperemic flow. beta-endo, A x beta-endo, beta-EER and A x beta-EER decreased significantly when the hyperemic flow was reduced by 75% or more. In contrast, SWT remained unchanged until the hyperemic flow was reduced by 90%. Among all parameters measured, beta-EER and A x beta-EER had the highest and SWT the lowest sensitivity and specificity in predicting mild myocardial ischemia. In conclusion, real-time MCE combined with dipyridamole stress allows for quantification of the transmural gradient of MBF. beta-EER and A x beta-EER are more sensitive than SWT and other MCE parameters in detecting mild myocardial ischemia. PMID- 17854986 TI - Modelling autonomy: simulating the essence of life and cognition. Introduction. PMID- 17854987 TI - Adsorption of phenol on a novel adsorption material PEI/SiO2. AB - In this paper, functional macromolecule polyethyleneimine (PEI) was grafted onto the surfaces of silica gel particles via the coupling effect of gamma chloropropyl trimethoxysilane (CP), and the novel adsorption material PEI/SiO2 with strong adsorption ability for phenol was prepared. The adsorption properties of PEI/SiO2 for phenol were researched by both static and dynamic methods. The experimental results show that PEI/SiO2 possesses very strong adsorption ability for phenol, and the saturated adsorption amount could reach to 160 mg g(-1). The empirical Freundlich isotherm was found to describe well the equilibrium adsorption data. pH and grafting amount of PEI have great influence on the adsorption amount. Diluted sodium hydroxide solution is used as eluent, and the adsorbed phenol is eluted easily from PEI/SiO2. PMID- 17854988 TI - Purification of spent chromium bath by membrane electrolysis. AB - The present study deals with the purification of spent chromium bath contaminated by trivalent chromium, iron and aluminum. The ionic transfer of Fe(III) depends on the presence of chloride ions on the pH while aluminum transfer is not affected by chromium(III) chloride. Five different commercial cation-exchange membranes were used. Nafion and PC-SK membranes showed the best results for trivalent iron and aluminum transfer. PMID- 17854989 TI - Reported tailings dam failures. A review of the European incidents in the worldwide context. AB - A detailed search and re-evaluation of the known historical cases of tailings dam failure was carried out. A corpus of 147 cases of worldwide tailings dam disasters, from which 26 located in Europe, was compiled in a database. This contains six sections, including dam location, its physical and constructive characteristics, actual and putative failure cause, sludge hydrodynamics, socio economical consequences and environmental impacts. Europe ranks in second place in reported accidents (18%), more than one third of them in dams 10-20 m high. In Europe, the most common cause of failure is related to unusual rain, whereas there is a lack of occurrences associated with seismic liquefaction, which is the second cause of tailings dam breakage elsewhere in the world. Moreover, over 90% of incidents occurred in active mines, and only 10% refer to abandoned ponds. The results reached by this preliminary analysis show an urgent need for EU regulations regarding technical standards of tailings disposal. PMID- 17854990 TI - VOC and carbonyl emissions from carpets: a comparative study using four types of environmental chambers. AB - Emissions of Volatile Organic Compounds (VOCs) and carbonyls from carpets of different type (wool, synthetic) over a time period of three days at 23 degrees C, at 45% relative humidity, 0.5 air change rate and a loading factor of 0.4 m(2) m(-3) were measured. The experiments were carried out at four different environmental chambers (volumes of 0.02/0.28/0.45/30 m(3)). For TVOCs, maximum concentrations up to 2300 microg m(-3) (for carpet with synthetic backing) were found. Aromatic compounds e.g. benzene, toluene, the xylenes and styrene are emitted in relatively low concentrations, while for 4-phenylcyclohexene and 2, 2 butoxyethoxy-ethanol concentrations up to 170 and 320 microg m(-3), respectively, were measured. In all experiments, emission rates reached the maximum value within few hours from the beginning of the experiment. The emission rates of TVOCs from the same type of carpet measured with various types of chambers (0.02/0.28/0.45/30 m(3)), exhibited differences of up to 75%. Chamber concentrations of carbonyls (formaldehyde, acetaldehyde, acetone and propanale) are of a few microg m(-3). Acetone and formaldehyde reach concentrations up to 15 and 10 microg m(-3), respectively. PMID- 17854991 TI - Removal of Zn(II), Cu(II), Ni(II), Ag(I) and Cr(VI) present in aqueous solutions by aluminium electrocoagulation. AB - The performance of an electrocoagulation system with aluminium electrodes for removing heavy metal ions (Zn2+, Cu2+, Ni2+, Ag+, Cr2O7(2-)) on laboratory scale was studied systematically. Several parameters - such as initial metal concentration, numbers of metals present, charge loading and current density - and their influence on the electrocoagulation process were investigated. Initial concentrations from 50 to 5000 mg L(-1) Zn, Cu, Ni and Ag did not influence the removal rates, whereas higher initial concentrations caused higher removal rates of Cr. Increasing the current density accelerated the electrocoagulation process but made it less efficient. Zn, Cu and Ni showed similar removal rates indicating a uniform electrochemical behavior. The study gave indications on the removal mechanisms of the investigated metals. Zn, Cu, Ni and Ag ions are hydrolyzed and co-precipitated as hydroxides. Cr(VI) was proposed to be reduced first to Cr(III) at the cathode before precipitating as hydroxide. PMID- 17854992 TI - Electrochemical remediation produces a new high-nitrogen compound from NTO wastewaters. AB - A new high-nitrogen molecule, identified as azoxytriazolone (AZTO), has been generated in high yield by electroreduction of acidic aqueous solutions of nitrotriazolone (NTO). The near-quantitative conversion appears to be driven by the low solubility of the product. AZTO precipitates readily, leaving the solution virtually free of organic material, and the process may therefore present an efficient and productive remediation method for wastewater from NTO manufacture. The chemical formula and molecular structure of AZTO indicate that it may be effective as an insensitive explosive. PMID- 17854993 TI - Blocking actions of alkylene-tethered bis-neonicotinoids on nicotinic acetylcholine receptors expressed by terminal abdominal ganglion neurons of Periplaneta americana. AB - Neonicotinoid insecticides target nicotinic acetylcholine receptors (nAChRs), which, in both vertebrates and invertebrates, mediate fast-acting synaptic neurotransmission in the nervous system. Recently, Kagabu et al. synthesized bis neonicotinoids. The neural activities of bis-neonicotinoids have been evaluated on the central nerve cord of American cockroaches. However, the action of bis neonicotinoids on nAChRs expressed by dissociated insect neurons has not yet been studied. Thus, the actions of several alkylene-tethered bis-neonicotinoids on the terminal abdominal ganglion neurons of the American cockroach, Periplaneta americana, were investigated using whole-cell patch-clamp electrophysiology. All of the ligands tested did not induce membrane currents, but reduced the responses to ACh when bath applied prior to co-application with ACh. Of the compounds tested, HK-13, which possesses two imidacloprid units linked with a hexamethylene bridge, had the highest antagonist potency. The antagonist action was reduced, not only by elongating, but also by shortening the linker. PMID- 17854994 TI - Expression of vascular endothelial growth factor receptors Flt-1 and Flk-1 in embryonic rat forebrain. AB - To define better the putative targets of vascular endothelial growth factor (VEGF) in the developing brain we have examined the ontogeny of the two VEGF tyrosine kinase receptors, Flt-1 and Flk-1, in embryonic rat forebrain. Semiquantitative reverse transcriptase-polymerase chain reaction and immunoblot analysis showed expression of both receptors in the forebrain at all embryonic ages studied. Messenger RNAs for Flt-1 and Flk-1 appeared along most of the ventricular zone of the lateral ventricle as early as embryonic day (E) 13. Messages gradually became restricted to a limited ventricular zone at E20. Expression of VEGF receptors was also observed in the cerebral cortex, hippocampus and thalamic nuclei. In the cortex, expression of mRNA for both receptors was detected in the cortical plate around E15, and became relatively weak and restricted to the deeper layers of the cortical plate at E20. These data suggest that VEGF may contribute to early developmental processes including the proliferation, differentiation and maturation of specific neuronal populations via specific VEGF receptors in the developing rat forebrain. PMID- 17854995 TI - Is pain relief equally efficacious and free of side effects with repeated doses of oral sucrose in preterm neonates? AB - The aim of the present study was to examine the efficacy and potential side effects of repeated doses of oral sucrose for pain relief during procedures in NICU. Thirty-three preterm neonates were randomly allocated in blind fashion into two groups, the sucrose group (SG=17) and the control group (CG=16). The responses of neonates to pain and distress were assessed during blood collection on four consecutive assessment (ass.) days. For the first assessment, the neonates did not receive any solution before the blood collection procedure. During the next three days, the SG received oral sucrose (25%; 0.5 ml/kg) and the CG received sterile water, 2 min before each minor acute painful procedure. The neonates were evaluated during blood collection each morning. The assessment was divided into five phases: Baseline (BL), Antisepsis (A), Puncture (P), Dressing (D), and Recovery (R). The neonates' facial activity (NFCS), behavioral state, and heart rate were evaluated. The data analysis used cut-off scores for painful and distressful responses. No side effects of using sucrose were detected. There were significantly fewer SG neonates with facial actions signaling pain than CG neonates in P (ass.2) and in A (ass.3). We found significantly fewer SG neonates in the awake state than CG neonates in P (ass.2 and ass.4). There were significantly fewer SG neonates crying during A (ass.2), P (ass.2 and ass.4), and D (ass.3). There was no statistical difference between-groups for physiological response. The efficacy of sucrose was maintained for pain relief in preterm neonates with no side effects. PMID- 17854996 TI - Of mice and men: what can we predict from the effects of morphine in a mouse model of bone cancer? PMID- 17854997 TI - A quantitative analysis of the cone-angle dependence in precession electron diffraction. AB - Precession electron diffraction (PED) is a technique which is gaining increasing interest due to its ease of use and reduction of the dynamical scattering problem in electron diffraction. To further investigate the usefulness of this technique, we have performed a systematic study of the effect of precession angle on the mineral andalusite where the semiangle was varied from 6.5 to 32 mrad in five discrete steps. The purpose of this study was to determine the optimal conditions for the amelioration of kinematically forbidden reflections, and the measurement of valence charge density. We show that the intensities of kinematically forbidden reflections decay exponentially as the precession semiangle (varphi) is increased. We have also determined that charge density effects are best observed at moderately low angles (6.5-13 mrad) even though PED patterns become more kinematical in nature as the precession angle is increased further. PMID- 17854998 TI - First reports of autochthonous eyeworm infection by Thelazia callipaeda (Spirurida, Thelaziidae) in dogs and cat from France. AB - Thelazia callipaeda (Spirurida, Thelaziidae) is a small nematode living in the conjunctival sac of domestic and wild carnivores, rabbits and humans causing lacrimation, epiphora, conjunctivitis, keratitis and even corneal ulcers. The first autochthonous cases of thelaziosis affecting four dogs and one cat living in South Western France (Dordogne area) are reported and described. Nematodes recovered from the animals were morphologically identified as T. callipaeda and a partial region of the cytochrome oxidase c subunit 1 gene (cox1) was amplified by PCR from nematode specimens (from two dogs and the cat). In each case, this was shown to have an identical sequence to the haplotype 1 (h1) of T. callipaeda. So far, the arthropod acting as intermediate host of T. callipaeda eyeworms has not been identified in France although it might be Phortica variegata (Steganinae, Drosophilidae) as recently described in Italy. PMID- 17854999 TI - Use of comparative proteomics to identify potential resistance mechanisms in cancer treatment. AB - Drug resistance is a major problem in successful cancer chemotherapy. Many molecular mechanisms that are responsible for drug resistance are known whereas others have yet to be discovered. Determining the exact mechanism activated in a particular case (clinical or laboratory) is a difficult task. Recently, proteomics has been applied to investigate drug resistance mechanisms in model cancer cell lines. As a result, novel mechanisms of resistance have been discovered and known mechanisms of resistance confirmed. In this paper, we wish to review recent developments and progresses in the application of proteomic tools to identify known and novel drug resistance mechanisms in drug-selected model cancer cell lines. Our combined analyses of multiple proteomic studies of various drug resistant cancer cell lines revealed that many mechanisms of resistance likely exist in any given drug-selected cancer cell line and that common mechanisms of resistance may be selected in a spectrum of cancer cell lines. These observations suggest that combination therapies targeting multiple mechanisms to sensitize drug resistant cancers may be necessary to eradicate cancers in the future. PMID- 17855000 TI - The effect of depression, anxiety and early life trauma on the cortisol awakening response during pregnancy: preliminary results. AB - The purpose of this study was to examine the effects of maternal depression and anxiety on the cortisol awakening response (CAR), a marker of the hypothalamic pituitary-adrenal (HPA) axis function, during pregnancy. Sixty-six pregnant women were studied between 25 and 33 weeks of gestation and were identified as either Depressed (n=33) or healthy, Control (n=33), based on depression scores and lifetime psychiatric history. Saliva samples were collected (passive drool) upon awakening and at +30 and +60 min thereafter. The CAR was not significantly different between women who were depressed during pregnancy compared to healthy control women. However, women taking antidepressant (AD) medication showed an attenuated CAR (time x AD use interaction, p=0.06). Childhood maltreatment (as measured with the Childhood Trauma Questionnaire) was associated with a lower baseline cortisol concentration explaining 12% of the variance, controlling for wake-up time and AD use. There is a complex interplay of factors involved in the HPA axis regulation of vulnerable women during pregnancy, including depression, anxiety, early life stress and psychotropic medication use, which remain unclear. The CAR may provide important information about the maternal HPA axis during pregnancy and warrants further investigation in larger cohorts. PMID- 17855001 TI - Cholesterol gallstones and cancer of gallbladder (CAGB): molecular links. AB - There is a known association between cholesterol gallstones and cancer of gall bladder (CAGB). However, the exact relation is not clear. It is proposed they are linked at molecular level by the activity of the orphan nuclear receptors (ONRs) and ABC transporter pumps involved in cholesterol and xenobiotic efflux from the liver into bile. There is evidence that these two pathways are closely interlinked and influence each other. Genetic and environmental factors that upregulate these systems can lead to the simultaneous pumping of cholesterol (which precipitate as gallstones) and a food carcinogen into the bile in gall bladder; the latter causes malignant transformation. Aflatoxin B, a potent hepatocarcinogen, could be the culprit in endemic regions such as South America and North India. PMID- 17855002 TI - Investigating the potential of statin medications as a nitric oxide (NO) release agent to decrease decompression sickness: a review article. AB - Understanding the biochemical mechanisms influencing bubble pathophysiology may foster novel pharmacologic non-recompressive strategies that may prevent, ameliorate, and treat decompression sickness (DCS), and the injury sustained from arterial gas emboli (AGE) encountered in hyperbaric and hypobaric exposures, as well as in surgery and trauma. This review explores the biochemical effects of nitric oxide (NO) release agents, their potential impact on bubble pathophysiology, and possible use as a pharmacological intervention to reduce DCS risk and AGE injury. The hypotheses discussed contend that exogenous NO administration or mediators of endogenous NO up-regulation may reduce DCS risk and severity by mediating; (1) decreased populations of gaseous nuclei, (2) decreased bubble nuclei adherence, (3) depression of the deleterious bubble mediated inflammatory and coagulation cascades and (4) preservation of endothelial integrity, which may defend against bubble-mediated injury. Statin medications alter numerous biochemical, and biophysical processes, which may influence bubble formation. Statins preserve endothelial integrity, reduce ischemia/reperfusion injury, and depress the interdependent inflammatory and coagulation cascades via pleiotropic properties involving up-regulation of endothelial nitric oxide synthase (eNOS) and NO. Numerous studies are researching statins, for their potential efficacy in reducing primary and secondary morbidity and mortality from cardiocerebrovascular, inflammatory (autoimmune), and infectious (sepsis) disease. Additionally, statin-mediated lipid reduction may reduce bubble generation via alterations in plasma "rheology", and surface tension. The statins are attractive potential NO release with minimal adverse side effects, and proven long-term safety, that may potentially mitigate the risk and severity of DCS. We will elaborate on the insight gained into the mechanisms proven and hypothesized for NO-mediated reductions in bubble formation, and DCS incidence and severity, with a focus on the potential for statin medications, in addition to the direct NO-donor medications such as isosorbide mononitrate and nitroglycerine. PMID- 17855003 TI - Prevention of diabetes with rosiglitazone: Evidence of benefit or unexpected harm? PMID- 17855004 TI - Comparison of efficacy of regional and extensive clinical target volumes in postoperative radiotherapy for esophageal squamous cell carcinoma. AB - PURPOSE: To compare and analyze the effect of different clinical target volumes (CTVs) on survival rate after postoperative radiotherapy (RT) for esophageal squamous cell carcinoma (SCC). METHODS AND MATERIALS: We studied 102 patients who underwent postoperative RT after radical resection for esophageal SCC (T3/4 or N1). The radiation dose was > or =50 Gy. In the extensive portal group (E group, 43 patients), the CTV encompassed the bilateral supraclavicular region, all mediastinal lymph nodes, the anastomosis site, and the left gastric and pericardial lymphatic. In the regional portal group (R group, 59 patients), the CTV was confined to tumor bed and the lymph nodes in the immediate region of the primary lesion. The 1-, 3-, and 5-year survival rates were compared between the groups, and multivariate/univariate analysis for factors predicting survival was studied. RESULTS: For the entire group, the 1-, 3- and 5-year survival rates were 76.3%, 50.5%, and 42.9%, respectively (median survival, 30 months). The 1-, 3-, and 5-year survival rates were 76.5%, 52.1%, and 41.3%, respectively, in the E group and 76.2%, 49.2%, and 44.6%, respectively, in the R group (not significant). According to the multivariate analysis, N stage, number of lymph nodes with metastatic disease, and tumor length were the independent prognostic factors for survival. CONCLUSIONS: Using a regional portal in postoperative RT for esophageal SCC is not associated with compromised survival compared with extensive portal RT and therefore should be considered. N stage, number of affected lymph nodes, and tumor length predict poor survival. PMID- 17855005 TI - Open-label, long-term safety study of cevimeline in the treatment of postirradiation xerostomia. AB - PURPOSE: To assess the safety of long-term cevimeline treatment of radiation induced xerostomia in patients with head-and-neck cancer; and to assess the efficacy of cevimeline in these patients. METHODS AND MATERIALS: A total of 255 adults with head-and-neck cancer who had received more than 40 Gy of radiation 4 months or more before entry and had clinically significant salivary gland dysfunction received cevimeline hydrochloride 45 mg t.i.d. orally for 52 weeks. Adverse events (AEs), their severity, and their relationship to the study medication were assessed by each investigator. The efficacy assessment was based on subjects' global evaluation of oral dryness on a scale of 0 (none) to 3 (severe). RESULTS: Overall, 175 subjects (68.6%) experienced expected treatment related AEs, most mild to moderate. The most frequent was increased sweating (47.5%), followed by dyspepsia (9.4%), nausea (8.2%), and diarrhea (6.3%). Fifteen subjects (5.9%) experienced Grade 3 treatment-related AEs, of which the most frequent was increased sweating. Eighteen subjects (7.1%) reported at least one serious AE, and 45 subjects (17.6%) discontinued study medication because of an AE. The global efficacy evaluation at the last study visit showed that cevimeline improved dry mouth in most subjects (59.2%). Significant improvement was seen at each study visit in the mean change from baseline of the numeric global evaluation score (p < 0.0001). CONCLUSIONS: Cevimeline 45 mg t.i.d. was generally well tolerated over a period of 52 weeks in subjects with xerostomia secondary to radiotherapy for cancer in the head-and-neck region. PMID- 17855006 TI - Mastectomy with immediate expander-implant reconstruction, adjuvant chemotherapy, and radiation for stage II-III breast cancer: treatment intervals and clinical outcomes. AB - PURPOSE: To determine intervals between surgery and adjuvant chemotherapy and radiation in patients treated with mastectomy with immediate expander-implant reconstruction, and to evaluate locoregional and distant control and overall survival in these patients. METHODS AND MATERIALS: Between May 1996 and March 2004, 104 patients with Stage II-III breast cancer were routinely treated at our institution under the following algorithm: (1) definitive mastectomy with axillary lymph node dissection and immediate tissue expander placement, (2) tissue expansion during chemotherapy, (3) exchange of tissue expander for permanent implant, (4) radiation. Patient, disease, and treatment characteristics and clinical outcomes were retrospectively evaluated. RESULTS: Median age was 45 years. Twenty-six percent of patients were Stage II and 74% Stage III. All received adjuvant chemotherapy. Estrogen receptor staining was positive in 77%, and 78% received hormone therapy. Radiation was delivered to the chest wall with daily 0.5-cm bolus and to the supraclavicular fossa. Median dose was 5,040 cGy. Median interval from surgery to chemotherapy was 5 weeks, from completion of chemotherapy to exchange 4 weeks, and from exchange to radiation 4 weeks. Median interval from completion of chemotherapy to start of radiation was 8 weeks. Median follow-up was 64 months from date of mastectomy. The 5-year rate for locoregional disease control was 100%, for distant metastasis-free survival 90%, and for overall survival 96%. CONCLUSIONS: Mastectomy with immediate expander implant reconstruction, adjuvant chemotherapy, and radiation results in a median interval of 8 weeks from completion of chemotherapy to initiation of radiation and seems to be associated with acceptable 5-year locoregional control, distant metastasis-free survival, and overall survival. PMID- 17855007 TI - Outcomes in young women with breast cancer of triple-negative phenotype: the prognostic significance of CK19 expression. AB - PURPOSE: Basal-like carcinoma of the breast is associated with genetic instability and aggressive behavior. In this study, we evaluated the luminal cytokeratin marker CK-19 in young women with breast cancer treated with conservative surgery and radiation therapy (CS+RT). METHODS: Primary tumor specimens from a cohort of 158 young premenopausal women (range, 25-49 years) treated with CS+RT with a median follow-up of 6.25 years were constructed into a tissue microarray. The array was stained for ER, PR, HER2, CK19, and p53. The molecular profiles were correlated with clinical-pathologic factors, overall, local, and distant relapse-free survival. The association between CK19, other co variables, and outcome was assessed in a multivariate model. RESULTS: Positive expression of ER, PR, HER-2/neu, CK19, and p53 were 33.1%, 34.5%, 10.0%, 79.5%, and 20.9%, respectively. With 20 local relapses and 38 distant metastases, the 10 year overall, breast relapse-free, and distant relapse-free survival were 79.65%, 87.29%, and 67.35%, respectively. Tumor stage and nodal status were associated with distant relapse-free and overall survival. In multivariate analysis, CK19 negativity was a predictor poor local (RR, 3.54; 95% CI, 1.87-7.65; p < 0.01) distant (RR, 1.44; 95% CI, 0.86-2.70; p = 0.17), and overall survival (RR, 1.89; 95% CI, 1.04-3.55; p = 0.03). CONCLUSIONS: Lack of CK19 expression identifies a subset of patients with a significantly higher risk of local relapse. Distant relapse and overall survival rates also correlated with CK19 negativity. Further evaluation of the prognostic significance of basal and luminal cytokeratins in young women with breast cancer is warranted. PMID- 17855008 TI - Determination of respiratory motion for distal esophagus cancer using four dimensional computed tomography. AB - PURPOSE: To investigate the motion characteristics of distal esophagus cancer primary tumors using four-dimensional computed tomography (4D CT). METHODS AND MATERIALS: Thirty-one consecutive patients treated for esophagus cancer who received respiratory-gated 4D CT imaging for treatment planning were selected. Deformable image registration was used to map the full expiratory motion gross tumor volume (GTV) to the full-inspiratory CT image, allowing quantitative assessment of each voxel's displacement. These displacements were correlated with patient tumor and respiratory characteristics. RESULTS: The mean (SE) tidal volume was 608 (73) mL. The mean GTV volume was 64.3 (10.7) mL on expiration and 64.1 (10.7) mL on inspiration (no significant difference). The mean tumor motion in the x-direction was 0.13 (0.006) cm (average of absolute values), in the y direction 0.23 (0.01) cm (anteriorly), and in the z-direction 0.71 (0.02) cm (inferiorly). Tumor motion correlated with tidal volume. Comparison of tumor motion above vs. below the diaphragm was significant for the average net displacement (p = 0.014), motion below the diaphragm was greater than above. From the cumulative distribution 95% of the tumors moved less than 0.80 cm radially and 1.75 cm inferiorly. CONCLUSIONS: Primary esophagus tumor motion was evaluated with 4D CT. According to the results of this study, when 4D CT is not available, a radial margin of 0.8 cm and axial margin of +/-1.8 cm would provide tumor motion coverage for 95% of the cases in our study population. PMID- 17855009 TI - Phase I trial of neoadjuvant preoperative chemotherapy with S-1 and irinotecan plus radiation in patients with locally advanced rectal cancer. AB - PURPOSE: To determine the maximum tolerated dose (MTD) and recommended dose (RD) of irinotecan combined with preoperative chemoradiotherapy with S-1 in patients with locally advanced rectal cancer. PATIENTS AND METHODS: We gave preoperative radiotherapy (total dose, 45 Gy) to 23 patients with locally advanced (T3/T4) rectal cancer. Concurrently, S-1 was given orally at a fixed dose of 80 mg/m2/day on Days 1-5, 8-12, 22-26, and 29-33, and irinotecan was given as a 90-min continuous i.v. infusion on Days 1, 8, 22, and 29. The dose of irinotecan was initially 40 mg/m2/day and gradually increased to determine the MTD and RD of this regimen. RESULTS: Among the 4 patients who received 90 mg/m2 irinotecan, 2 had Grade 4 neutropenia and 1 had Grade 3 diarrhea. Because dose-limiting toxicity (DLT) occurred in 3 of the 4 patients, 90 mg/m2 irinotecan was designated as the MTD. Consequently, 80 mg/m2 irinotecan was given to 7 additional patients, with no DLT, and this was considered the RD. Of the patients who received irinotecan at the RD or lower doses, 6 (31.6%) had a complete pathologic response (Grade 3) and 9 (47.4%) underwent sphincter-preserving surgery. CONCLUSIONS: With our new regimen, the MTD of irinotecan was 90 mg/m2, and the RD of irinotecan for Phase II studies was 80 mg/m2. Although our results are preliminary, this new neoadjuvant chemoradiotherapy was considered safe and active, meriting further investigation in Phase II studies. PMID- 17855010 TI - Toxicity profile with a large prostate volume after external beam radiotherapy for localized prostate cancer. AB - PURPOSE: To assess the impact of prostate volume on health-related quality of life (HRQOL) before and at different intervals after radiotherapy for prostate cancer. METHODS AND MATERIALS: A group of 204 patients was surveyed prospectively before (Time A), at the last day (Time B), 2 months after (Time C), and 16 months (median) after (Time D) radiotherapy, with a validated questionnaire (Expanded Prostate Cancer Index Composite). The group was divided into subgroups with a small (11-43 cm(3)) and a large (44-151 cm(3)) prostate volume. RESULTS: Patients with large prostates presented with lower urinary bother scores (median 79 vs. 89; p = 0.01) before treatment. Urinary function/bother scores for patients with large prostates decreased significantly compared to patients with small prostates due to irritative/obstructive symptoms only at Time B (pain with urination more than once daily in 48% vs. 18%; p < 0.01). Health-related quality of life did not differ significantly between both patient groups at Times C and D. In contrast to a large prostate, a small initial bladder volume (with associated higher dose volume load) was predictive for lower urinary bother scores both in the acute and late phase; at Time B it predisposed for pollakiuria but not for pain. Patients with neoadjuvant hormonal therapy reached significantly lower HRQOL scores in several domains (affecting only incontinence in the urinary domain), despite a smaller prostate volume (34 cm(3) vs. 47 cm(3); p < 0.01). CONCLUSIONS: Patients with a large prostate volume have a great risk of irritative/obstructive symptoms (particularly dysuria) in the acute radiotherapy phase. These symptoms recover rapidly and do not influence long-term HRQOL. PMID- 17855011 TI - Liver function after irradiation based on computed tomographic portal vein perfusion imaging. AB - PURPOSE: To determine whether individual and regional liver sensitivity to radiation could be assessed by measuring liver perfusion during a course of treatment using dynamic contrast-enhanced computed tomography scanning. METHODS AND MATERIALS: Patients with intrahepatic cancer undergoing conformal radiotherapy underwent dynamic contrast-enhanced computed tomography (to measure perfusion distribution) and an indocyanine extraction study (to measure liver function) before, during, and 1 month after treatment. We hoped to determine whether the residual functioning liver (i.e., those regions showing portal vein perfusion) could be used to predict overall liver function after irradiation. RESULTS: Radiation doses from 45 to 84 Gy resulted in undetectable regional portal vein perfusion 1 month after treatment. The volume of each liver with undetectable portal vein perfusion ranged from 0 to 39% and depended both on the patient's sensitivity and on dose distribution. There was a significant correlation between indocyanine green clearance and the mean of the estimated portal vein perfusion in the functional liver parenchyma (p < 0.001). CONCLUSION: This study reveals substantial individual variability in the sensitivity of the liver to irradiation. In addition, these findings suggest that hepatic perfusion imaging may be a marker for liver function and has the potential to be a tool for individualizing therapy. PMID- 17855013 TI - Long-term clinical and functional outcomes after treatment for localized Ewing's tumor of the lower extremity. AB - PURPOSE: Retrospective review describing the 35-year University of Florida experience with Ewing's tumors of the lower extremity. PATIENTS AND METHODS: Fifty-three patients were treated between 1971 and 2006. Thirty patients were treated with radiotherapy (RT) alone and 23 patients were treated with surgery +/ RT. Larger tumors and tumors of the femur were treated more often with definitive RT. Median potential follow-up was 19.2 years. Functional outcome was assessed using the Toronto Extremity Salvage Score (TESS). RESULTS: Before 1985, 24% of patients were treated with surgery; since then, the rate has increased to 61%. The 15-year actuarial overall survival (OS), cause-specific survival (CSS), freedom from relapse, and limb preservation rates were 68% vs. 47% (p = 0.21), 73% vs. 47% (p = 0.13), 73% vs. 40% (p = 0.03), and 43% vs. 40% (p = 0.52), respectively, for patients treated with surgery +/- RT vs. RT alone. Excluding 8 patients who underwent amputation or rotationplasty, the 15-year actuarial local control rate was 100% for the surgery +/- RT group and 68% for the definitive RT group (p = 0.03). The ranges of the TESS for surgery +/- RT vs. RT alone were 70 100 (mean, 94) and 97-100 (mean, 99), respectively. Twenty-six percent (6/23) of patients had complications related to surgery requiring amputation or reoperation. CONCLUSIONS: Overall survival and CSS were not statistically compromised, but we observed an increased risk of relapse and local failure in patients treated with RT alone, thereby justifying a transition toward primary surgical management in suitable patients. However, despite an adverse risk profile, patients treated with RT alone had similar long-term amputation-free survival and demonstrated comparable functional outcomes. Poor results observed in Ewing's of the femur mandate innovative surgical and RT strategies. PMID- 17855012 TI - Radiotherapy does not influence the severe pulmonary toxicity observed with the administration of gemcitabine and bleomycin in patients with advanced-stage Hodgkin's lymphoma treated with the BAGCOPP regimen: a report by the German Hodgkin's Lymphoma Study Group. AB - PURPOSE: To evaluate the effect of radiotherapy on the severe pulmonary toxicity observed in the pilot study of BAGCOPP (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, and gemcitabine) for advanced-stage Hodgkin's lymphoma. METHODS AND MATERIALS: Patients with Stage III or IV Hodgkin's lymphoma or Stage IIB with risk factors participated in this single arm, multicenter pilot study. RESULTS: Twenty-seven patients were enrolled on the study before its premature closure as a result of the development of serious pulmonary toxicity in 8 patients. The pulmonary toxicity occurred either during or immediately after the BAGCOPP chemotherapy course. Pulmonary toxicity contributed to one early fatality but resolved in the other 7 patients after cessation of gemcitabine and bleomycin, allowing continuation of therapy. Fifteen patients received consolidative radiotherapy, including 4 who previously had pulmonary toxicity. There were no reported cases of radiation pneumonitis and no exacerbation of pulmonary symptoms in the 4 patients who had had previous pulmonary toxicity. CONCLUSIONS: The severe pulmonary toxicity observed in this study has been attributed to an interaction between gemcitabine and bleomycin. Gemcitabine (when administered without bleomycin) remains of interest in Hodgkin's lymphoma and is being incorporated into a new German Hodgkin's Lymphoma Study Group protocol that also includes consolidative radiotherapy. This study supports the concept of the integration of radiotherapy in gemcitabine-containing regimens in Hodgkin's lymphoma if there is an interval of at least 4 weeks between the two modalities and with a schedule whereby radiotherapy follows the chemotherapy. PMID- 17855014 TI - Adjuvant brachytherapy removes survival disadvantage of local disease extension in stage IIIC endometrial cancer: a SEER registry analysis. AB - PURPOSE: To assess the role of radiotherapy (RT) in women with Stage IIIC endometrial cancer. METHODS AND MATERIALS: The 17-registry Survival, Epidemiology, and End Results (SEER) database was searched for patients with lymph node-positive non-Stage IV epithelial endometrial cancer diagnosed and treated between 1988 and 1998. Two subgroups were identified: those with organ confined Stage IIIC endometrial cancer and those with Stage IIIC endometrial cancer with direct extension of the primary tumor. RT was coded as external beam RT (EBRT) or brachytherapy (BT). Observed survival (OS) was reported with a minimum of 5 years of follow-up; the survival curves were compared using the log rank test. RESULTS: The therapy data revealed 611 women with Stage IIIC endometrial cancer during this period. Of these women, 51% were treated with adjuvant EBRT, 21% with EBRT and BT, and 28% with no additional RT (NAT). Of the 611 patients, 293 had organ-confined Stage IIIC endometrial cancer and 318 patients had Stage IIIC endometrial cancer with direct extension of the primary tumor. The 5-year OS rate for all patients was 40% with NAT, 56% after EBRT, and 64% after EBRT/BT. Adjuvant RT improved survival compared with NAT (p <0.001). In patients with organ-confined Stage IIIC endometrial cancer, the 5-year OS rate was 50% for NAT, 64% for EBRT, and 67% for EBRT/BT. Again, adjuvant RT contributed to improved survival compared with NAT (p = 0.02). In patients with Stage IIIC endometrial cancer and direct tumor extension, the 5-year OS rate was 34% for NAT, 47% for EBRT, and 63% for EBRT/BT. RT improved OS compared with NAT (p <0.001). Also, in this high-risk subgroup, adding BT to EBRT was superior to EBRT alone (p = 0.002). CONCLUSION: Women with Stage IIIC endometrial cancer receiving adjuvant EBRT and EBRT/BT had improved OS compared with patients receiving NAT. When direct extension of the primary tumor was present, the addition of BT to EBRT was even more beneficial. PMID- 17855015 TI - Intrarectal amifostine during external beam radiation therapy for prostate cancer produces significant improvements in Quality of Life measured by EPIC score. AB - PURPOSE: To test whether intrarectal amifostine limits symptoms of radiation proctitis, measured by using the Radiation Therapy Oncology Group (RTOG) gastrointestinal (GI) toxicity score and the Expanded Prostate Cancer Index Composite (EPIC) score. METHODS AND MATERIALS: Patients with localized prostate cancer received amifostine as a rectal suspension 30-45 minutes before daily three-dimensional conformal radiation therapy. The first 18 patients received 1 g of amifostine, and the next 12 patients received 2 g. Toxicity was assessed at baseline, during treatment, and at follow-up visits by using RTOG grading and the EPIC Quality of Life (QoL) 50-item questionnaire. The Bowel Function subset of the bowel domain (EPIC-BF), which targets symptom severity, and the Bowel Bother subset of the bowel domain (EPIC-BB), which assesses QoL, were evaluated and compared with the RTOG GI toxicity score. RESULTS: Median follow-up was 30 months (range, 18-36 months). Overall, EPIC-BF and EPIC-BB scores both tracked closely with the RTOG GI toxicity score. Seven weeks after the start of radiation therapy, the incidence of RTOG Grade 2 toxicity was 33% in the 1-g group (6/18 patients) compared with 0% (0/12 patients) in the 2-g group and tended toward statistical significance (p = 0.06). A significant difference between amifostine groups was observed using the EPIC-BF score at 7 weeks (p = 0.04). A difference in EPIC-BB scores between dose groups was evident at 7 weeks (p = 0.07) and was significant at 12 months (p = 0.04). CONCLUSIONS: Higher doses of amifostine produced significant improvements in acute and late bowel QoL (up to 1 year after therapy), measured using the EPIC score. PMID- 17855016 TI - Effect of postmastectomy radiotherapy in patients <35 years old with stage II-III breast cancer treated with doxorubicin-based neoadjuvant chemotherapy and mastectomy. AB - PURPOSE: Postmastectomy radiotherapy (PMRT) improves locoregional control (LRC) in patients with high-risk features after mastectomy. Young age continues to evolve as a potentially important risk factor. The objective of this study was to assess the benefits of PMRT in patients <35 years old treated with doxorubicin based neoadjuvant chemotherapy for Stage II-III breast cancer. PATIENTS AND METHODS: We retrospectively analyzed 107 consecutive breast cancer patients <35 years old with Stage IIA-IIIC disease treated at our institution with doxorubicin based neoadjuvant chemotherapy and mastectomy, with or without PMRT. The treatment groups were compared in terms of LRC and overall survival. RESULTS: Despite more advanced disease stages, the patients who received PMRT (n = 80) had greater rates of LRC (5-year rate, 88% vs. 63%, p = 0.001) and better overall survival (5-year rate, 67% vs. 48%, p = 0.03) than patients who did not receive PMRT (n = 27). CONCLUSION: Among breast cancer patients <35 years old at diagnosis, the use of PMRT after doxorubicin-based neoadjuvant chemotherapy and mastectomy led to a statistically greater rate of LRC and overall survival compared with patients without PMRT. The benefit seen for PMRT in young patients provides valuable data to better tailor adjuvant, age-specific treatment decisions after mastectomy. PMID- 17855017 TI - Flavonoids with DNA strand-scission activity from Rhus javanica var. roxburghiana. AB - The flavonoids isolated from the stems of Rhus javanica var. roxburghiana, taxifolin (1), fisetin (2), fustin (3), 3,7,4'-trihydroxyflavanone (4) and 3,7,4' trihydroxyflavone (5) caused breakage of supercoiled plasmid pBR322 DNA in the presence of Cu(II). Cu(I) was shown to be an essential intermediate by using the Cu(I)-specific sequestering reagent neocuproine. The Cu(II)-mediated DNA scissions induced by 1, 2, 3 and 5 were inhibited by the addition of catalase and exhibited DNA strand break by the addition of KI and superoxide dimutase (SOD), while in the Cu(II)-mediated DNA scissions induced by 4 was inhibited by the addition of KI, SOD, and catalase. It is concluded that 1, 2, 3, and 5 can induce H2O2 and superoxide anion, while 4 can induce OH* and H2O2 and subsequent oxidative damage of DNA in the presence of Cu(II). PMID- 17855018 TI - An ethnobotanical survey of medicinal plants used by the Didayi tribe of Malkangiri district of Orissa, India. AB - An ethnobotanical survey was carried out among the ethnic community (Didayi) in Malkangiri district, Orissa. A total of 53 medicinal plant species belonging to 34 families and 52 different species are described under this study. PMID- 17855019 TI - Antidiabetic potential of Phyllanthus reticulatus in alloxan-induced diabetic mice. AB - The plant Phyllanthus reticulatus is claimed to have antidiabetic activity in tribal area. To validate the tribal claim, the petroleum ether and ethanolic extracts of leaves of the P. reticulatus were orally tested at 500 and 1000 mg/kg for hypoglycemic effect in alloxan induces diabetic mice. It shows antidiabetic activity at the dose of 1000 mg/kg. The phytochemical screening of the residues revealed the presence of terpenoids glycosides, protein, carbohydrates and absence of alkaloids and steroids. PMID- 17855020 TI - Four new prenylated flavonoids and xanthones from the root bark of Artocarpus nobilis. AB - Chemical investigation of the n-butanol extract from the methanol extract of the root bark of Artocarpus nobilis furnished four new prenylated flavonoids together with artonin E 2'-methylether (4), isoartonin E 2'-methylether (5), dihydroisoartonin E 2'-methylether (6), artonin V 2'-methylether (7), artobiloxanthone (1), artonin E (2) and cycloartobiloxanthone (3). All these compounds showed strong radical scavenging properties towards DPPH radical. PMID- 17855021 TI - Echinacea alkylamides modulate induced immune responses in T-cells. AB - The effects of Echinacea and several of its phytochemical components on NFkappaB expression by Jurkat cells (a human T-cell line) were investigated in vitro. In the absence of stimulation, Echinacea and its components exerted no significant effect on basal NFkappaB expression levels. In the presence of endotoxin (LPS), NFkappaB expression was decreased. However, this decrease was significantly reversed by treatment with cichoric acid, an Echinacea root extract (prepared from both Echinacea angustifolia and Echinacea purpurea) and the alkylamide fraction derived from this combination. For the phorbol myristate acetate stimulation of Jurkat cells, effects on NFkappaB expression were mixed. Depending on the concentration, cichoric acid and a 2,4-diene alkylamide significantly induced NFkappaB levels, whereas a 2-ene alkylamide caused a significant inhibition. In contrast, both the Echinacea and the mixed alkylamide fraction exerted no effect. The alkylamide results indicate that the two basic forms of these compounds present in Echinacea may have opposing effects. These opposing effects demonstrate the importance of a knowledge, not only of the phytochemical make-up of a herbal preparation, but also of the actions of each component and the consequences of differing relative amounts in the preparation being investigated. PMID- 17855022 TI - Antioxidant activity of Pyrrosia petiolosa. AB - The ethanol extract of Pyrrosia petiolosa showed an antioxidant activity as determined by free radical scavenging, superoxide radical scavenging, lipid peroxidation, and hydroxyl radical-induced DNA strand scission assays. PMID- 17855023 TI - Three divergent mitochondrial genomes from California populations of the copepod Tigriopus californicus. AB - Previous work on the harpacticoid copepod Tigriopus californicus has focused on the extensive population differentiation in three mtDNA protein coding genes (COXI, COXII, Cytb). In order to get a more complete understanding of mtDNA evolution in this species, we sequenced three complete mitochondrial genomes (one from each of three California populations) and compared them to two published mtDNA genomes from an Asian congener, Tigriopus japonicus. Several features of the mtDNA genome appear to be conserved within the genus: 1) the unique order of the protein coding genes, rRNA genes and most of the tRNA genes, 2) the genome is compact, varying between 14.3 and 14.6 kb, and 3) all genes are encoded on the same strand of the mtDNA. Within T. californicus, extremely high levels of nucleotide divergence (>20%) are observed across much of the mitochondrial genome. Inferred amino acid sequences of the proteins encoded in the mtDNAs also show high levels of divergence; at the extreme, the three ND3 variants in T. californicus showed >25% amino acid substitutions, compared with <3% amino acid divergence at the previously studied COXI locus. Unusual secondary structures make functional assignments of some tRNAs difficult. The only apparent tRNA(trp) in these genomes completely overlaps the 5' end of the 16S rRNA in all three T. californicus mtDNAs. Although not previously noted, this feature is also conserved in T. japonicus mtDNAs; whether this sequence is processed into a functional tRNA has not been determined. The putative control region contains a duplicated segment of different length (from 88 to 155 bp) in each of the T. californicus sequences. In each case, the duplicated segments are not tandem repeats; despite their different lengths, the distance between the start of the first and the start of the second repeat is conserved (520 bp). The functional significance, if any, of this repeat structure remains unknown. PMID- 17855024 TI - Structure and evolution of RIM-BP genes: identification of a novel family member. AB - RIM-binding proteins (RIM-BPs) were identified as binding partners of the presynaptic active zone proteins RIMs as well as for voltage-gated Ca(2+) channels. They were suggested to form a functional link between the synaptic vesicle fusion apparatus and Ca(2+)-channels. Here we show that the RIM-BP gene family diversified in different stages during evolution, but retained their unique domain structure. While invertebrate genomes contain one, and vertebrates include at least two RIM-BPs, we identified an additional gene, RIM-BP3, which is exclusively expressed in mammals. RIM-BP3 is encoded by a single exon of which three copies are present in the human genome. All RIM-BP genes encode proteins with three SH3-domains and two to three fibronectin III repeats. The flanking regions diverge in size and sequence and are alternatively spliced in RIM-BP1 and -2. Quantitative real-time RT-PCR and in situ hybridization analyses revealed overlapping but distinct expression patterns throughout the brain for RIM-BP1 and -2, while RIM-BP3 was detected at high levels outside the nervous system. The modular domain structure of RIM-BPs, their expression pattern and the conservative expansion during evolution shown here support their potential role as important molecular adaptors. PMID- 17855025 TI - Real-time multiplex PCR assays for reliable detection of Clostridium perfringens toxin genes in animal isolates. AB - Typing of Clostridium perfringens strains by PCR-based determination of toxin genes proved to be a reliable method for diagnosis of enterotoxaemia in various animal species. We report the establishment and validation of three real-time fluorogenic (TaqMan) multiplex PCRs for the detection of C. perfringens alpha-, beta-, beta2-, epsilon-, entero- and iota-toxin genes. The composition of the PCRs was chosen with regard to robustness of the assays and in order to increase sensitivity compared to the conventional simplex PCRs. The combination of probe dyes selected for the real-time assays (FAM/TAMRA, Cy-5/BHQ-2 and VIC/TAMRA) as well as the designation of the chromosome-borne alpha-toxin as internal positive control allowed the creation of highly specific and sensitive, as well as time and cost effective PCRs. One hundred and three strains of C. perfringens isolated in Switzerland derived from clinical or suspected cases of enterotoxaemia in 10 different animal species were tested. The toxin genotypes were in agreement in both the conventional PCRs and the newly designed multiplex PCRs. Furthermore, the real-time PCR carried out as simplex allows to quantitate the copy numbers of plasmid-borne toxin genes in relation to the chromosomally located alpha-toxin gene. PMID- 17855026 TI - Structural characterization and serological specificities of lipopolysaccharides from Salmonella enterica serovar Gallinarum biovar Pullorum standard, intermediate and variant antigenic type strains. AB - The structure and serological specificities of the lipopolysaccharides (LPSs) from Salmonella enterica serovar Gallinarum biovar Pullorum were studied to provide an improved basis for the distinction between antigenic types and the development of improved diagnostic tests. The structure of the LPS O polysaccharide (O-PS) from S. Pullorum standard, intermediate and variant antigenic type strains was determined by mass spectrometry, nuclear magnetic resonance spectroscopy and chemical analysis. The LPS of the three strains shared a common structural repeating oligosaccharide unit containing d-mannose, l rhamnose, d-galactose and d-tyvelose (1:1:1:1). The O-PS of the variant type LPS contained an additional d-glucose residue linked to the O-4 position of the d galactose residue. The O-PS of the intermediate type LPS was partially the same as that of the variant LPS, however, the molar ratio of the d-glucose component was lower with respect to the other glycose components. Serological specificities of the three antigenic type LPSs were examined with anti-S. Pullorum LPS monoclonal antibodies (Mabs). On immunoblots, Mabs to the standard type O-PS reacted with high molecular mass (HMM) and low molecular mass (LMM) LPS from the standard strain, and with LMM but not HMM LPS from the variant strain. Monoclonal antibodies to the variant type O-PS reacted with HMM but not LMM LPS from the variant strain, and did not react with HMM or LMM LPS from the standard strain. On ELISA, the standard, intermediate and variant antigenic type strains were differentiated by the relative reactivity with the anti-LPS O-PS Mabs. Several of the anti-LPS O-PS Mabs were specific for S. Pullorum and other serogroup D1 Salmonella, and are potentially useful for the development of improved diagnostic tests for these organisms. PMID- 17855027 TI - Lead contamination results in late and slowly repairable DNA double-strand breaks and impacts upon the ATM-dependent signaling pathways. AB - Despite a considerable amount of data, evaluation of the potential genotoxicity and cancer proneness of lead compounds remains unclear, probably due to the plethora of experimental procedures, biological endpoints and cellular models used. In parallel, the understanding in DNA damage formation, repair and signaling has considerably progressed all along these last years, notably for DNA double-strand breaks (DSBs). Here, were examined DNA damage formation and repair in human cells exposed to lead nitrate (Pb(NO(3))(2)) and their consequences upon the ATM-dependent stress signaling, cell cycle progression and cell death. As observed with anti-pH2AX immunofluorescence, exposure to Pb(NO(3))(2) results in formation of late DSBs, that would not originate from conversion of nucleotide damage but likely by a direct production of single-strand breaks. Lead contamination inhibits non-homologous end-joining repair process by preventing the DNA-PK kinase activity whereas the MRE11-dependent repair pathway is exacerbated. Lead contamination triggers successive synchronization of cells in G2/M phase in which the RAD51-dependent homologous recombination was found to be activated. Altogether, our findings support that lead contamination generates late unrepairable DSBs that impact upon the ATM-dependent stress signaling pathway by favoring propagation of errors. Such findings should help to consider more carefully the biological action of lead compounds in the frame of public and occupational exposures. PMID- 17855028 TI - Organic extract of tire debris causes localized damage in the plasma membrane of human lung epithelial cells. AB - The potential toxicity of tire debris organic extracts on human alveolar epithelial cells (A549) was investigated. We analysed time- and dose dependent modifications produced on plasma membrane molecular composition and on lipid microdomains expression (caveolae and lipid rafts) that represent specific signalling platforms. Cells were exposed to increasing organic extract concentrations (10, 60 and 75mug/ml) for 24, 48 and 72h. An up to three fold dose and time dependent increase in specific protein markers of lipid microdomains was found, suggesting a corresponding increase in signalling platforms. Since the total pool of these plasma membrane markers was unchanged, we supposed that these proteins were translocated within the plasma membrane as to assemble the newly formed lipid microdomains. Despite no major modifications in lipid bilayer composition, a time- and dose dependent toxic effect was documented at 48h of exposure by an increase of cells positive to Trypan Blue assay. After 48h a dose dependent increase in the cell medium of the cytosolic enzyme lactate dehydrogenase was also observed, indicating greater damage of the plasma membrane as prenecrotic sign. The overall ultrastructural morphology of the plasma membrane of treated cells was not greatly modified, suggesting that organic extracts from tire debris cause focalized discontinuities on cell surfaces. PMID- 17855029 TI - Inhibition of blood platelet adhesion, aggregation and secretion by Artemisia dracunculus leaves extracts. AB - BACKGROUND: Platelet hyperactivity plays an important role in atherosclerosis and arterial thrombosis. Artemisia dracunculus L. (tarragon) is a common table vegetable all over Iran and known for its anticoagulant activity in Iranian folk medicine. OBJECTIVE: The present study was undertaken to investigate the effect of Artemisia dracunculus leaves methanol crude extract and its chloroform fraction on platelet aggregation, secretion and adhesion to laminin coated plates. MATERIALS AND METHODS: Human platelets were incubated with different concentrations of the test sample (equivalent to 25-200 mug of plant leaves powder/ml). The treated and untreated platelets were then activated with thrombin and adhesion to the laminin coated plates were evaluated. RESULTS: Based on our observations, the methanol extract and its chloroform fraction, at a concentration of 200 mug/ml, inhibited platelet adhesion to laminin coated wells by 50% and 60%, respectively. In addition to alternation of cell adhesive properties, protein secretion and self aggregation of the treated platelets were decreased upon treatment with the crude extract and its chloroform fraction. CONCLUSIONS: Our results showed that the methanol crude extract and chloroform fraction of tarragon could inhibit platelets adhesion, aggregation and secretion. These findings provide scientific basis for the traditional use of tarragon as a blood-diluting factor, as locally called, or as an anticoagulant. PMID- 17855030 TI - Antinociceptive and anti-inflammatory effects of compounds isolated from Scaphyglottis livida and Maxillaria densa. AB - Oral administration of a CH(2)Cl(2)-MeOH (1:1) extract of Scaphyglottis livida produced dose-dependent antinociceptive and anti-inflammatory effects when tested in mice and rats using the hot-plate (150-600 mg/kg) and carrageenan-induced inflammation (150-600 mg/kg) models, respectively. Morphine (1.5-6 mg/kg, p.o.) and indomethacin (10-40 mg/kg, p.o.) were used as positive controls, respectively. Four compounds were isolated from the active extract of Scaphyglottis livida, namely 5alpha-lanosta-24,24-dimethyl-9(11),25-dien-3beta-ol (LDD), 24,24,dimethyl-9,19-cyclolanosta-9(11),25-dien-3-one (cyclobalanone), gigantol and 3,4'-dihydroxy-3',4,5-trimethoxybibenzyl (DTB). LDD and gigantol (25 100 mg/kg, p.o.) significantly increased the hot-plate latency in comparison to vehicle-treated mice and decreased carrageenan-induced inflammation in rats. The antinociception provoked by LDD and gigantol was partially blocked by naloxone (1mg/kg, i.p.). However, pretreatment with L-NAME (100 mg/kg, i.p.) and glibenclamide (10 mg/kg, i.p.) did not affect the antinociceptive response induced by LDD or gigantol suggesting that their pharmacological effect could be partially due to activation of opioid receptors. Moreover, a CH(2)Cl(2)-MeOH (1:1) extract of Maxillaria densa reduced acetic acid-induced abdominal writhes but was not able to produce antinociception in the hot-plate assay. Two compounds were isolated from the active extract of Maxillaria densa, namely fimbriol A and erianthridin. Both compounds partially reduced acetic acid-induced writhes. The results tend to support the popular use of this species in folk medicine for treatment of painful complaints. PMID- 17855031 TI - Cardiac metastasis of tongue cancer may cause sudden death. AB - OBJECTIVE: To identify cardiac metastases in a patient with a squamous cell carcinoma of the tongue and to clarify the relationship between cardiac metastases and sudden death. STUDY DESIGN: Autopsy and retrospective chart review for a patient. METHODS: We studied a Japanese patient who suddenly died after the operation and radiation therapy, despite an absence of thanatoid symptoms. We performed a subsequent autopsy. RESULTS: The patient had four metastatic lesions in the heart, one of which was in the septum and infiltrated the region around the conducting system of the heart. CONCLUSION: Cardiac metastasis of tongue cancer may cause sudden death. PMID- 17855032 TI - Vagus nerve paralysis due to skull base fracture. AB - Lower cranial nerve paralysis originating from skull base fracture is rare and isolated vagus nerve paralysis after close head injury is extremely rare. We, in this study, present the case of a 49-year-old man sustained a right vocal cord paralysis and dysphagia in a fighting accident. Initial examination, including flexible laryngoscope, esophagogram and fine-cut neck computed tomography scan, failed to find out the cause of isolated vagus paralysis. Until high resolution computed tomography of skull base revealed the jugular foramen bony disruption. One individual cranial nerve paralysis may be a significant sign for skull base fracture in closed head injury. Considering the serious consequences of the disease, thorough neurologic and radiologic examination are needed to evaluate the condition of skull base, and to develop reliable effective management for the neurologic sequalae, result from it. PMID- 17855033 TI - Endolymphatic sac papillary tumor: a case report and review. AB - Endolymphatic sac papillary tumor (endolymphatic sac adenoma, temporal-mastoid bone adenoma or adenocarcinoma, low-grade adenocarcinoma of potential endolymphatic sac origin, aggressive papillary tumor of the temporal bone, Heffner's tumor) is a rare lesion that involves the temporal bone. This tumor usually appears alone, but in 11-30% of afflicted individuals, it is accompanied by von Hippel-Lindau disease. Endolymphatic sac papillary tumors are destructive tumors that exhibit locally aggressive behavior. They slowly grow into the posteromedial section of petrous temporal bone. The main symptoms produced by these lesions include hearing loss and cranial nerve deficits. Endolymphatic sac papillary tumors develop in two principal patterns that histopathologically form follicular and papillary or solid structures. Those two patterns are usually manifested in the same tumor. Immunochemical analysis of these tumors usually reveals cytokeratin, vimentin, epithelial membrane antigen, and (less frequently) S-100 protein and neuron-specific enolase. Local excision is curative for endolymphatic sac papillary tumors. The currently favored method of treatment consists of excision and long-term follow-up. The role of adjuvant radiotherapy as treatment is controversial. This case report describes an endolymphatic sac tumor in a 22-year-old woman without von Hippel-Lindau disease who had a number of complaints, including deafness in her left ear, complete left-sided facial paralysis, and hoarseness of approximately 8 years' duration. PMID- 17855034 TI - [Acute Vibrio parahaemolyticus gastroenteritis in Dakar]. AB - OBJECTIVES: The aim of this study was to describe the epidemiological, clinical and bacteriological features of gastroenteritis due to Vibrio parahaemolyticus diagnosed during the 2004 and 2005 cholera outbreak in Senegal. PATIENTS AND METHODS: This retrospective study was made on data recorded between October 11, 2004 and December 31, 2005 at Dakar Fann Hospital. The diagnosis of V. parahaemolyticus was made after identification in stool cultures. RESULTS: Thirty five cases of V. parahaemolyticus gastroenteritis were identified, accounting for 8.7% of bacterial gastroenteritis (35/403) and 1.18% of all cholera-like gastroenteritis (35/2942). The patients' median age was 26 years [range=10-70 years] and the M/F sex ratio was 1.5. Most patients came from Dakar city (30 cases). Contamination occurred within the family in 27 cases, and food was suspected to be the source of contamination in 33 cases. Clinical presentation upon admission included acute watery diarrhea with dehydration (35 cases), vomiting (30 cases), abdominal pain (25 cases), muscular cramps (12 cases), and fever (4 cases). All V. parahaemolyticus isolates were susceptible to amoxicillin, quinolones, cotrimoxazole, chloramphenicol, and cyclines. Patients were treated by rehydration and doxycycline. The outcome was favorable in all cases, with a mean hospital stay of 24 hours [range=4-72 hours]. PMID- 17855035 TI - Improvement and decline in health status from late middle age: modeling age related changes in deficit accumulation. AB - In a prospective multi-panel cohort study, we investigated how, from late middle age, individuals' health status improves or declines. In the Canadian National Population Health Survey, transition probabilities between different health states were estimated for 4330 people (58.8% women) aged 55+ at baseline over 2 year intervals from 1994 to 2000. Health status was defined by a deficit count, using 33 health-related variables combined in a frailty index. For each time interval, the chance of accumulating deficits increased linearly with the number of deficits. Older survivors (aged 70-85) showed a slightly lower chance of stability or improvement (52%; 95% confidence interval 50-54%) compared with those in late middle age (56%; 54-58%). Changes in health states can be described with high accuracy (R2=0.92) by a modified Poisson distribution, using four parameters: the background odds of accumulating additional deficits, the chance of incurring more or fewer deficits, given the existing number, and the corresponding probabilities of dying. An age-invariant limit to deficit accumulation was observed at 22 deficits. From late middle age, transitions in health states occur with a regularity that is easily modeled. Improvements in health can occur at any age. At all ages, there is a limit to deficit accumulation. PMID- 17855036 TI - Sonographic findings of the median nerve and prevalence of carpal tunnel syndrome in patients with Parkinson's disease. AB - PURPOSE: Parkinson's disease (PD) is a chronic progressive disorder which is characterized by rest tremor, akinesia or bradykinesia and rigidity. Carpal tunnel syndrome (CTS) is caused by compression of median nerve and can occur as a result of repetitive trauma. The aim of this study was to estimate the prevalence of CTS in PD and evaluate the median nerve sonographically. MATERIALS AND METHODS: Fifty-three wrist of 29 patients with PD were included in the study according to Hoehn and Yahr (H&Y) clinical stage and divided into two groups. The first group consisted of 29 wrists of patients with mild PD (H&Y stage I-II). The second group consisted of 24 wrists of patients with severe PD (H&Y stage III IV). Thirty-six wrists of 20 age-matched patients were used as control group. Both of the patients with PD and control group underwent sonography and electromyography (EMG). Axial sonograms of the median nerve were obtained at the level of distal radioulnar joint (level 1) and at the level of pisiform bone in the carpal tunnel (level 2). At each level, the cross-sectional area of the median nerve and flattening ratio were calculated. RESULTS: There was no significant difference for all parameters, except one parameter, between the patients with PD and control group, and also among mild and severe groups of PD and control group (p>0.05). Interestingly, amplitude of median nerve in the second finger was significantly lower in PD patients than control group within normal limits (p=0.010). Of all wrists of PD patients, 13 (24.4%) have been diagnosed as CTS and 7 (19.4%) control wrists had CTS. Median nerve cross sectional area of CTS patients were more than 10mm(2) in 6 (46%) wrists of PD patients but in only 1 (14%) control wrist at each level. Although it was not statistically significant, there was higher cross-sectional area at each level in patients with severe PD (level 1: 10.43+/-2.30 mm(2), level 2: 10.35+/-3.19 mm(2)) than patients with mild PD (level 1: 9.93+/-2.61 mm(2), level 2: 9.51+/ 2.83 mm(2)) and control group (level 1: 9.69+/-3.19 mm(2), level 2: 9.07+/-3.61 mm(2)). CONCLUSION: PD may pose a risk for the development of CTS due to the repetitive movement of tremor. Although sonography is not an ideal method of diagnosis for CTS, it may take our attention for indicating CTS in patients with PD especially in severe ones. PMID- 17855037 TI - Enantioselective liquid chromatography-mass spectrometry assay for the determination of ifosfamide and identification of the N-dechloroethylated metabolites of ifosfamide in human plasma. AB - A sensitive and specific liquid chromatography-mass spectrometry (LC-MS) method has been developed and validated for the enantioselective determination of ifosfamide [(R)-IF and (S)-IF] in human plasma and for the detection of the N dechloroethylated metabolites of IF, 2-N-dechloroethylifosfamide [(R)-2-DCl-IF and (S)-2-DCl-IF] and 3-N-dechloroethylifosfamide [(R)-3-DCl-IF and (S)-3-DCl IF]. IF, 2-DCl-IF and 3-DCl-IF were extracted from plasma using solid-phase extraction and resolved by liquid chromatography on a column containing a Chirabiotic T chiral stationary phase. The enantioselective separations were achieved using a mobile phase composed of 2-propanol:methanol (60:40, v/v) and a flow rate of 0.5 ml/min. The observed enantioselectivities (alpha) for IF, 2-DCl IF and 3-DCl-IF were 1.20, 1.17 and 1.20, respectively. The calibration curve was linear in the concentration range of 37.50-4800 ng/ml for each ifosfamide enantiomer (r(2)>0.997). The lower limit of detection (LLOD) was 5.00 ng/ml. The inter- and intra-day precision ranged from 3.63 to 15.8% relative standard deviation (R.S.D.) and 10.1 to 14.3% R.S.D., respectively, and the accuracy ranged from 89.2 to 101.5% of the nominal values. The method was applied to the analysis of plasma samples obtained from a cancer patient who received 3.75 g/m(2)/day dose of (R,S)-ifosfamide as a 96-h continuous infusion. PMID- 17855038 TI - Comparison of the aggregation behavior of soy and bovine whey protein hydrolysates. AB - Soy-derived proteins (soy protein isolate, glycinin, and beta-conglycinin) and bovine whey-derived proteins (whey protein isolate, alpha-lactalbumin, beta lactoglobulin) were hydrolyzed using subtilisin Carlsberg, chymotrypsin, trypsin, bromelain, and papain. The (in)solubility of the hydrolysates obtained was studied as a function of pH. At neutral pH, all soy-derived protein hydrolysates, particularly those from glycinin, obtained by hydrolysis with subtilisin Carlsberg, chymotrypsin, bromelain, and papain showed a stronger aggregation compared to the non-hydrolyzed ones. This increase in aggregation was not observed upon hydrolysis by trypsin. None of the whey-derived protein hydrolysates exhibited an increase in aggregation at neutral pH. The high abundance of theoretical cleavage sites in the hydrophobic regions of glycinin probably explains the stronger exposure of hydrophobic groups than for the other proteins, which is suggested to be the driving force in the aggregate formation. PMID- 17855039 TI - Enzyme-induced aggregation and gelation of proteins. AB - This paper provides a brief overview of the effects of protein hydrolysis on aggregation and gel forming properties of protein systems. Among the food globular proteins, whey proteins and soy proteins are the most extensively studied for their ability to form different textures upon proteolysis. Recent studies were focused on identifying aggregating peptides and on mechanisms of aggregation and gelation. PMID- 17855040 TI - Self-assembly of partially hydrolysed alpha-lactalbumin. AB - Hydrolysis of the whey protein alpha-lactalbumin with a specific serine protease has been shown to result in regular nanotubes of approximately 20 nm in outer diameter and reaching several mum in length. Tubular assembly depends on the concentration of protein as this determines how far the hydrolysis proceeds. A concentration of 30 g L(-1) is a prerequisite for tubular formation, as is a minimum concentration of calcium. At lower protein concentrations calcium independent formation of linear fibrils (approximately 5 nm in diameter) is favoured. Possible applications of alpha-lactalbumin nanotubes include use as a viscosifier and gelling agent and also pharmaceutical utilization (such as targeted drug release) and use in nanotechnology can be envisioned. PMID- 17855041 TI - Effect of non-protein components on the degradability of proteins. AB - Two major groups of non-protein components effects the degradability of proteins. The first one includes the major nutrients and their degradation products e.g. of carbohydrates and fats, which may undergo the typical "MAILLARD" reaction with proteins. The second one includes those minor components represented e.g. by the indigenous group of secondary plant metabolites. This paper focuses on protein degradability as effected by interactions of proteins with secondary plant metabolites giving special attention to the group of phenolic compounds. PMID- 17855042 TI - Patients' perspectives on the role of radiation therapists. AB - OBJECTIVE: To examine patients' perspectives on the role of radiation therapists and to develop substantive theory about the relationships patients form with their radiation therapists. METHODS: Semi-structured interviews were conducted with 34 breast cancer patients in Western Australia. Interviews were tape recorded and transcribed verbatim. Grounded theory and the constant comparative method were used to analyse the data. RESULTS: The major finding from this study was the importance that patients placed on achieving a sense of emotional comfort during their radiation therapy. Two ways in which patients achieved this comfort were by forming relationships with radiation therapists and gaining information related to their treatment and care. CONCLUSION: Radiation therapists played a central role in enabling patients to achieve a sense of emotional comfort. Although radiation therapists have a technical job they need to remain aware of their role in providing patient care and take appropriate steps to ensure that they can assist patients in feeling comfortable during their radiation therapy. PRACTICE IMPLICATIONS: The role of the radiation therapist in assisting patients to achieve a sense of emotional comfort needs to be formalised to ensure that all patients in radiation therapy are aware of the radiation therapist's role and receive a similar level of care during treatment. PMID- 17855043 TI - [Analgesia in particular situation: pregnant woman]. PMID- 17855044 TI - [Alzheimer's disease: a major piece of work for Public Health in France]. PMID- 17855045 TI - [Chronic renal failure in patients aged more than 50 years in general practice: an epidemiological survey among a sample of 1034 patients]. PMID- 17855046 TI - [Mild cognitive impairment]. AB - The concept of mild cognitive impairment (MCI) was proposed by Petersen et al. (1997, 1999) as a nosologic entity referring to elderly persons with mild cognitive deficit and without dementia. MCI is widely used in studies as an intermediate stage between cognitive normalcy and dementia. MCI now appears, however, to be a heterogeneous clinical entity. The many sources of heterogeneity that have been pointed out include: heterogeneity in etiological factors (various types of degenerative lesions, vascular risk factors, psychiatric features, concomitant non-neurological diseases), in clinical symptoms, and in clinical course (with decline, stable, or reversible cognitive impairment). New clinical criteria have thus been proposed for use in research and in clinical practice: 1) cognitive complaint from the patient, family, or both, 2) report by the subject or reporter of a decline in cognitive or functional performance, relative to previous abilities, 3) cognitive disorders evidenced by clinical evaluation: impairment in memory or another cognitive domain, 4) cognitive impairment without any repercussions on daily life, even if the subject reports difficulties concerning complex daily activities, and 5) no dementia. Those new criteria, essentially clinical, may be better adapted to both clinical research and daily clinical practice. Biological and radiological markers will provide greater and more systematic support for diagnosis in the near future, particularly for early detection of Alzheimer's disease. PMID- 17855047 TI - Influence of aqueous crude extracts of medicinal plants on the osmotic stability of human erythrocytes. AB - This work analyzed the effects of the aqueous crude extracts of Artemisia absinthium L., Lippia sp., Bryophyllum sp., Solidago microglossa DC, Cymbopogon citratus DC and Mentha x villosa HUDSON on the osmotic stability of human erythrocytes. Hemolysis was monitored by measurement of absorbance at 540 nm following addition of erythrocytes to NaCl solutions of varying concentration. Absorbance was fitted to sigmoid regression curves given by the Boltzmann equation, and hemolysis was characterized by the NaCl concentration leading to lysis of 50% of cells (H(50)), and by the intensity (H) and the amplitude (dS) of the lysis effect. The parameters were determined in the absence and presence of the crude extracts. The extracts of Artemisia absinthium, Lippia sp., C. citratus and M. villosa protected human erythrocytes against hypotonic shock, as evidenced by a decrease in the values of H and H(50) compared to the control solution (p<0.05). The extracts of Bryophyllum sp. and S. microglossa enhanced hemolysis, since their H(50) values were higher than in the control group (p<0.05), but they also showed protective effects, as evidenced by a decrease in H and an increase in dS. PMID- 17855048 TI - High frequency of mosaic CREBBP deletions in Rubinstein-Taybi syndrome patients and mapping of somatic and germ-line breakpoints. AB - Rubinstein-Taybi syndrome (RSTS) is a rare malformation disorder caused by mutations in the closely related CREBBP and EP300 genes, accounting respectively for up to 60 and 3% of cases. About 10% of CREBBP mutations are whole gene deletions often extending into flanking regions. Using FISH and microsatellite analyses as a first step in the CREBBP mutation screening of 42 Italian RSTS patients, we identified six deletions, three of which were in a mosaic condition that has not been previously reported in RSTS. The use of region-specific BAC clones and small CREBBP probes allowed us to assess the extent of all of the deletions by mapping their endpoints to genomic intervals of 5-10 kb. Four of our five intragenic breakpoints cluster at the 5' end of CREBBP, where there is a peak of breakpoints underlying rearrangements in RSTS patients and tumors. The search for genomic motifs did not reveal any low-copy repeats (LCRs) or any greater density of repetitive sequences. In contrast, the percentage of interspersed repetitive elements (mainly Alu and LINEs in the CREBBP exon 2 region) is significantly higher than that in the entire gene or the average in the genome, thus suggesting that this characteristic may be involved in the region's vulnerability to breaking and nonhomologous pairing. The FISH analysis extended to the EP300 genomic region did not reveal any deletions. The clinical presentation was typical in all cases, but more severe in the three patients carrying constitutional deletions, raising a question about the possible underdiagnosis of a few cases of mild RSTS. PMID- 17855049 TI - Effect of doxycycline treatment during pregnancy for birth outcomes. PMID- 17855050 TI - Theory of Mind "emotion", developmental characteristics and social understanding in children and adolescents with intellectual disabilities. AB - Patterns of development of ToM-emotion abilities in intellectually disabled (ID) children and typically developing (TD) children matched on their developmental age were investigated. The links between cognition, language, social understanding and ToM-emotion abilities were examined. EDEI-R (Perron-Borelli, M. (1996). Echelles Differentielles d'Efficiences Intellectuelles. Forme Revisee (EDEI-R). Paris: Editions et Applications Psychologiques) was used to match participants and to assess social understanding. ECOSSE (Lecocq, P. (1996). L'E.CO.S.SE. Une epreuve de comprehension syntaxico-semantique. Paris: Presses Universitaires du Septentrion) assessed the level of syntactic and semantic comprehension of French speaking, to ensure a good comprehension of the questions in ToM-emotion tasks. Adapted tasks of the understanding of causes and consequences of emotions (Quintal, G. (2001). La comprehension des emotions chez les enfants d'age prescolaire dans le cadre d'une theorie de l'esprit. Un published master's thesis, University of Montreal, Quebec) assessed ToM-emotion abilities (Nader-Grosbois, N., Thirion-Marissiaux, A.-F., & Grosbois, M. (2003). Adapted tests for assessment of the Theory of Mind of causes and consequences of emotions (unpublished documents). Louvain-la-Neuve, Belgium). Similarities in the development of ToM-emotion abilities and social understanding were found, respectively, in both groups (delay hypothesis in ID participants). Some differences between groups were observed in the links between social understanding and ToM-emotion abilities. Significant correlations between developmental characteristics (verbal and non-verbal cognition) and ToM-emotion abilities were obtained for both groups. Verbal cognition explained an important part of the variance of ToM results (understanding of causes and consequences of emotions). The impact of chronological age on ToM-emotion abilities was also examined and is discussed. PMID- 17855051 TI - Bid is not required for Bax translocation during UV-induced apoptosis. AB - UV irradiation triggers apoptosis through both the membrane death receptor and the intrinsic apoptotic signaling pathways. Bax, a member of the Bcl-2 family of proteins, translocates from the cytosol to the mitochondrial membrane during UV induced apoptosis, but the regulation of Bax translocation by UV irradiation remains elusive. In this study, we show that Bax translocation, caspase-3 activation and cell death by UV irradiation are not affected by Z-IETD-fmk (caspase-8 inhibitor), but delayed by Pifithrin-alpha (p53 inhibitor), although Bid cleavage could be completely abolished by Z-IETD-fmk. Co-transfecting YFP-Bax and Bid-CFP into human lung adenocarcinoma cells, we demonstrate that translocation of YFP-Bax precedes that of Bid-CFP, there is no significant FRET (fluorescence resonance energy transfer) between them. Similar results are obtained in COS-7 cells expressing YFP-Bax and Bid-CFP. Furthermore, using acceptor photobleaching technique, we observe that there is no interaction between YFP-Bax and Bid-CFP in both healthy and apoptotic cells. Additionally, during UV-induced apoptosis there is downregulation of Bcl-x(L), an anti apoptotic protein. Overexpression of Bcl-x(L) in cells susceptible to UV-induced apoptosis prevents Bax translocation and cell death, repression of Bid protein with siRNA (small interfering RNA) do not inhibit cell death by UV irradiation. Taken together, these data strongly suggest that Bax translocation by UV irradiation is a Bid-independent event and inhibited by overexpression of Bcl x(L). PMID- 17855052 TI - Early myeloid cells expressing c-KIT isoforms differ in signal transduction, survival and chemotactic responses to Stem Cell Factor. AB - Isoforms of the receptor tyrosine kinase, c-KIT, differ in the presence or absence of a GNNK tetrapeptide in the extracellular juxtamembrane region. When expressed in murine NIH3T3 cells, these isoforms of c-KIT showed differential activation of signaling pathways and proliferation in response to Stem Cell Factor (SCF). However, c-KIT is not normally expressed by fibroblasts, but plays a key role in hematopoiesis. Because signaling pathways and cellular responses mediated by c-KIT differ in different cell types, we studied the effects of SCF stimulation on factor-dependent murine early myeloid cells expressing human GNNK+ or GNNK- c-KIT. As in fibroblasts, SCF activation of the GNNK- isoform resulted in stronger, more rapid receptor phosphorylation, and activation of Src kinases, while only a minor effect on the phosphatidylinositol 3-kinase pathway was observed. Similarly, more rapid Src kinase-dependent internalisation of the GNNK- isoform occurred in response to SCF. In contrast to fibroblasts, only minor differences in ERK activation were seen indicating that early hematopoietic cells, unlike fibroblasts, are not dependent on Src kinases for activation of this pathway in response to SCF. Enhanced SCF-dependent growth was observed in GNNK- c-KIT expressing cells due to lower cell attrition. The rate of cell division was similar. Importantly, cells expressing the GNNK- isoform showed a greater chemotactic response to SCF. PMID- 17855053 TI - The association of Sam68 with Vav1 contributes to tumorigenesis. AB - Vav1 functions in the hematopoietic system as a specific GDP/GTP nucleotide exchange factor regulated by tyrosine phosphorylation. An intact C-terminal SH3 domain of Vav1 (Vav1SH3C) was shown to be necessary for Vav1-induced transformation, yet the associating protein(s) necessary for this activity have not yet been identified. Using a proteomics approach, we identified Sam68 as a Vav1SH3C-associating protein. Sam68 (Src-associated in mitosis of 68 kD) belongs to the heteronuclear ribonucleoprotein particle K (hnRNP-K) homology (KH) domain family of RNA-binding proteins. The Vav1/Sam68 interaction was observed in vitro and in vivo. Mutants of Vav1SH3C previously shown to lose their transforming potential did not associate with Sam68. Co-expression of Vav1 and Sam68 in Jurkat T cells led to increased localization of Vav1 in the nucleus and changes in cell morphology. We then tested the contribution of Sam68 to known functions of Vav1, such as focus-forming in NIH3T3 fibroblasts and NFAT stimulation in T cells. Co expression of oncogenic Vav1 with Sam68 in NIH3T3 fibroblasts resulted in a dose dependent increase in foci, yet no further enhancement of NFAT activity was observed in Jurkat T cells, as compared to cells overexpressing only Vav1 or Sam68. Our results strongly suggest that Sam68 contributes to transformation by oncogenic Vav1. PMID- 17855054 TI - Early bone formation in human bone grafts treated with platelet-rich plasma: preliminary histomorphometric results. AB - The aim of this study was to evaluate the effect of platelet-rich plasma (PRP) on early and late bone healing after autogenous maxillary sinus grafting. Eleven patients were subjected to sinus augmentation with particulated autogenous bone bilaterally with the addition of PRP in one side. Platelet counts in baseline whole blood and PRP were registered. Biopsies were taken in the grafted bone of the sinus area with trephine at 3 months (nine patients) and simultaneously a micro-implant was installed in the same region. The micro-implants with surrounding bone were retrieved by biopsy at 6 months (seven patients). Undecalcified cut and ground sections were histomorphometrically analysed. Quantification of new and old bone in all biopsies was performed. The results of this histological study showed that significantly more new bone was formed at PRP treated sites compared to controls after 3 months of healing. After 6 months, this effect could no longer be observed. This is in accordance with previous studies showing that PRP has a rather low regenerative capacity but may influence the early phase of bone healing. The additional value of PRP in autogenous bone grafts in the maxillary sinus is questionable. PMID- 17855055 TI - Memantine normalizes brain activity in the inferior frontal gyrus: a controlled pilot fMRI study. PMID- 17855056 TI - Disturbed social behavior and motivation in rats selectively bred for deficient sensorimotor gating. AB - Deficient prepulse inhibition (PPI) of startle reflects disturbed sensorimotor gating found in certain neuropsychiatric disorders. We here tested whether rats selectively bred for deficient PPI are deteriorated in behavioral paradigms used to model negative symptoms of schizophrenia. Rats with low PPI preferred standard rat-chow when having the choice between lever-pressing for reward-pellets or freely available rat-chow, suggesting reduced motivation. Additionally, these rats show deteriorated social behavior during interaction with a juvenile rat. Rats selectively bred for low PPI may therefore be used as a model to study the biological mechanisms and therapeutic strategies of negative symptoms of schizophrenia. PMID- 17855057 TI - Blunted activation in right ventrolateral prefrontal cortex during motor response inhibition in schizophrenia. AB - OBJECTIVES: Previous functional magnetic resonance imaging (fMRI) studies have reported abnormal brain activation in individuals with schizophrenia during performance of motor inhibition tasks. We aimed to clarify brain functional abnormalities related to motor response inhibition in schizophrenia by using event-related fMRI in combination with a Go-NoGo task designed to control for non inhibitory cognitive processes involved in task performance. METHOD: We studied 21 schizophrenic patients and 21 healthy subjects, group-matched for age, sex, and performance accuracy on a Go-NoGo task during event-related fMRI. The task was designed so that Go and NoGo events were equally probable. Between-group activation differences were assessed using ANCOVAs with response time and IQ as covariates of non-interest. RESULTS: Compared to healthy subjects, schizophrenic patients exhibited a significant decrease in activation during motor response inhibition in the right ventrolateral prefrontal cortex (VLPFC) only. There were no areas of increased brain activation in patients compared to healthy subjects. CONCLUSIONS: Schizophrenic patients demonstrate a blunted activation in the right VLPFC, a region known to play a critical role in motor response inhibition. Further research should ascertain the contribution of the VLPFC dysfunction to the impulsive behavior observed in schizophrenia. PMID- 17855058 TI - Does hyperpriming reveal impaired spreading of activation in schizophrenia? PMID- 17855059 TI - Novel keratin 5 mutations in epidermolysis bullosa simplex: cases with unusual genotype-phenotype correlation. PMID- 17855060 TI - On an invisible microbe antagonistic toward dysenteric bacilli: brief note by Mr. F. D'Herelle, presented by Mr. Roux. 1917. PMID- 17855061 TI - A high-sensitive amperometric hydrogen peroxide biosensor based on the immobilization of hemoglobin on gold colloid/L-cysteine/gold colloid/nanoparticles Pt-chitosan composite film-modified platinum disk electrode. AB - A hemoglobin (Hb)/gold colloid (nano-Au)/L-cysteine (L-cys)/nano-Au/nanoparticles Pt (nano-Pt)-chitosan (CHIT) composite film-modified platinum disk electrode (abbreviated to modified electrode) has been prepared to construct a biosensor for determination of H(2)O(2). The electrochemical characteristics of the biosensor were studied by cyclic voltammetry and chronoamperometry. The modified process was characterized by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The morphologies of different composite film were investigated with scanning electron microscopy (SEM) and the element of composite film was investigated with X-ray photoelectron spectroscopy (XPS). Analytical parameters such as pH and temperature were also studied. The linear range for the determination of H(2)O(2) is 1.4 x 10(-7) to 6.6 x 10(-3)mol/L with a detection limit of 4.5 x 10(-8)mol/L (S/N=3). The sensor achieved 95% of the steady-state current within 10s. The sensor exhibited high sensitivity (17.62 microA/(mmol L)), selectivity and stability. The method is applied to the determination of H(2)O(2) with satisfactory results. PMID- 17855062 TI - Cyclin D1 overexpression in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric adenocarcinomas. AB - Changes in cell cycle regulation are involved in many human cancers, including gastric cancer. In the present study, cyclin D1 expression and localization were immunohistochemically analyzed in 23 N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric adenocarcinomas and compared with findings for beta-catenin. Cyclin D1 nuclear overexpression was more frequently observed in tumors displaying nuclear (4/4=100%) and cytoplasmic (3/4=75%) beta-catenin accumulation than those with membranous (3/15=20%) localization (nuclear vs. membranous, P<0.02). In the former cases it was considered that cyclin D1 was induced with beta-catenin activation; in the latter, a direct or indirect pathway for cyclin D1 accumulation bypassing Wnt pathway might be involved. Cyclin D1 was also found to be accumulated in gastric glands within normal-looking mucosa, these perhaps representing preneoplastic lesions for cancers with membranous beta-catenin accumulation. PMID- 17855063 TI - Expression of Ki-67 in the uterus during various stages of the estrous cycle in rats. AB - Rats have an average estrous cycle of 4-5 days. There are four phases (proestrus, estrus, metesterus, and diestrus) in the estrous cycle in rodents. Histologic staging of the rodent estrous cycle is challenging and requires expertise. Thus, utilizing additional parameters such as cellular proliferation of the various components of the uterine microanatomy may assist with this process. Having an alternative method by which a pathologist can correctly identify the stages of the rodent estrous cycle would be valuable to the assessment and interpretation of safety studies for new drug candidates. This study was performed to investigate the microanatomic location of the uterine proliferative activity by image analysis and immunohistochemistry using Ki-67, a well-established marker of proliferating cells. Each stage of the rodent estrous cycle exhibited a different pattern of cellular proliferation. During proestrus, the lowest degree of cellular proliferation occurred in the glandular epithelial cells and the highest occurred in the myometrial cells. In estrus, lower levels of cellular proliferation were seen in the luminal and glandular epithelial cells, while a higher rate of proliferation occurred in myometrial cells followed by the stromal cells. At the metestrus stage, the highest cellular proliferation occurred in stromal and myometrial cells, while lesser proliferation was observed in luminal and glandular epithelial cells. This work demonstrates that in the rodent uterus there are cyclic changes in cellular proliferation in specific microanatomic uterine locations which can aid in the staging of the estrous cycle. PMID- 17855064 TI - Fatty acid composition of human spermatozoa and seminal plasma levels of oxidative stress biomarkers in subfertile males. AB - INTRODUCTION: The lipid composition of the sperm membrane has a significant effect on the functional characteristics of spermatozoa. PATIENTS AND METHODS: In the present study, fatty acid composition of spermatozoa and seminal plasma levels of free 15-F(2t)-Isoprostane and catalase were assayed in men with normozoospermia, asthenozoospermia, asthenoteratozoospermia, and oligoasthenoteratozoospermia. RESULTS: In spermatozoa from asthenozoospermic men only oleic acid levels showed a significant difference from normozoospermic men. In spermatozoa from asthenoteratozoospermic and oligoasthenoteratozoospermic samples all of the tested fatty acids were significantly higher than those from normozoospermic samples. Seminal plasma levels of catalase were significantly lower in all patients while levels of free 15-F(2t)-Isoprostane were significantly higher in all patients compared with normozoospermic men. DISCUSSION: Spermatozoa from pathological samples may have higher levels of polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), than spermatozoa from normozoospermic men. Therefore, damage induced by lipid peroxidation would be higher in spermatozoa from pathological samples than those from normozoospermic men. PMID- 17855065 TI - Hypogonadism in male outpatients with sarcoidosis. AB - Hypogonadism is assumed to be present in sarcoidosis. Nevertheless, a comparison of circulating sex hormone concentrations of male sarcoidosis patients with those of healthy men has never been done. Moreover, it remains unknown if hypogonadism may contribute to a reduced muscle function, exercise intolerance, diminished vitality and depressed mood in male sarcoidosis patients. Pulmonary function, muscle function, exercise tolerance, vitality, mood, circulating sex hormone concentrations and C-reactive protein were assessed in 30 male sarcoidosis patients and 26 age-matched men with a normal pulmonary function. On average, patients had a restrictive pulmonary function, worse inspiratory and quadriceps muscle function, functional exercise intolerance, diminished vitality, depressed mood and increased systemic inflammation. Moreover, patients had significantly lower circulating (free) testosterone concentrations, while circulating sex hormone-binding globulin tended to be lower (p=0.0515). Circulating gonadotrophin concentrations were comparable. Non-significant relationships were found between sex hormones, clinical outcomes and C-reactive protein in patients with sarcoidosis. A significant number of male outpatients with sarcoidosis (46.7%) had low circulating testosterone concentrations, which was most probably caused by hypogonadotrophism. The clinical relevance of hypogonadism in male outpatients with sarcoidosis, however, remains currently unknown. Indeed, poor inspiratory and quadriceps muscle function, exercise intolerance, diminished vitality and depressed mood were not related to hypogonadism in these patients. PMID- 17855066 TI - CHKS data should be avoided when investigating mortality. PMID- 17855067 TI - Inhibitory effect of dietary n-3 polyunsaturated fatty acids to intestinal IL-15 expression is associated with reduction of TCRalphabeta+CD8alpha+CD8beta intestinal intraepithelial lymphocytes. AB - Intestinal intraepithelial lymphocytes (IELs) and their cytokines play an important role in the regulation of gut immune response and take part in gut immune barrier function. n-3 polyunsaturated fatty acid (PUFA) is an immunoregulator that has been shown to influence the process of gut inflammation. Interleukin (IL)-15 is a T-cell growth factor that has been shown to influence the differentiation of IEL. The aim of this study was to analyze the effects of dietary n-3 PUFA on IEL. IEL phenotype and cytokine (TNF-alpha, IFN-gamma, IL-4, IL-10 and TGF-beta1) profile were measured by FACS and real-time RT-PCR in healthy adult rats fed with fish oil diet for 90 days. Rats fed with corn oil diet served as controls. Intestinal IL-15 expression was measured by immunohistochemistry and real-time RT-PCR. The results demonstrated a decrease of intestinal IL-15 expression in the fish oil group. Associated with this deduction, n-3 PUFA significantly decreased the proportion of TCRalphabeta+CD8alpha+CD8beta- cells and IEL-derived TNF-alpha, IFN-gamma, IL-4 and IL-10. In conclusion, n-3 PUFA could inhibit intestinal mucosal expression of IL-15 and may influence phenotype and function of IEL through this mechanism. PMID- 17855068 TI - Oxidative stress-induced risk factors associated with the metabolic syndrome: a unifying hypothesis. AB - Although the biochemical steps linking insulin resistance with the metabolic syndrome have not been completely clarified, mounting experimental and clinical evidence indicate oxidative stress as an attractive candidate for a central pathogenic role since it potentially explains the appearance of all risk factors and supports the clinical manifestations. In fact, metabolic syndrome patients exhibit activation of biochemical pathways leading to increased delivery of reactive oxygen species, decreased antioxidant protection and increased lipid peroxidation. The described associations between increased abdominal fat storage, liver steatosis and systemic oxidative stress, the diminished concentration of nitric oxide derivatives and antioxidant vitamins and the endothelial oxidative damages observed in subjects with the metabolic syndrome definitively support oxidative stress as the common second-level event in a unifying pathogenic view. Moreover, it has been observed that oxidative stress regulates the expression of genes governing lipid and glucose metabolism through activation or inhibition of intracellular sensors. Diet constituents can modulate redox reactions and the oxidative stress extent, thus also acting on nuclear gene expression. As a consequence of the food-gene interaction, metabolic syndrome patients may express different disease features and extents according to the different pathways activated by oxidative stress-modulated effectors. This view could also explain family differences and interethnic variations in determining risk factor appearance. This review mechanistically focused on oxidative stress events leading to individual disease factor appearance in metabolic syndrome patients and their setting for a more helpful clinical approach. PMID- 17855069 TI - Physical analyses of compost from composting plants in Brazil. AB - Nowadays the composting process has shown itself to be an alternative in the treatment of municipal solid wastes by composting plants. However, although more than 50% of the waste generated by the Brazilian population is composed of matter susceptible to organic composting, this process is, still today, insufficiently developed in Brazil, due to low compost quality and lack of investments in the sector. The objective of this work was to use physical analyses to evaluate the quality of the compost produced at 14 operative composting plants in the Sao Paulo State in Brazil. For this purpose, size distribution and total inert content tests were done. The results were analyzed by grouping the plants according to their productive processes: plants with a rotating drum, plants with shredders or mills, and plants without treatment after the sorting conveyor belt. Compost quality was analyzed considering the limits imposed by the Brazilian Legislation and the European standards for inert contents. The size distribution tests showed the influence of the machinery after the sorting conveyer on the granule sizes as well as the inert content, which contributes to the presence of materials that reduce the quality of the final product. PMID- 17855070 TI - An evaluation of substrate degradation patterns in the composting process. Part 2: temperature-corrected profiles. AB - In this paper, the patterns of 44 substrate degradation profiles obtained from the composting literature are examined following their correction to a constant temperature of 40 degrees C, using a new procedure presented in this work. The applicability of a single exponential model, a double exponential model and a non logarithmic Gompertz model in describing their behaviour is then evaluated. Multi phase profiles were most commonly seen, with convex shapes observed in only a relatively small proportion of the profiles. Convex shapes were also embedded within other profiles, either preceeded by a lag phase, or followed by non-convex behaviour. Sigmoidal patterns were relatively rare. Of the temperature-corrected data sets examined, 33 were found to be either not well modelled by, or inappropriate for, any of the above models. Two fits rated as good were obtained when using the single exponential model, and one fit rated as excellent, plus one fit rated as good, were obtained when using the double exponential model. A single fit rated as excellent was found when using the non-logarithmic Gompertz model. The lag phase, which was observed in many data sets, was successfully modelled using the non-logarithmic Gompertz function where excellent and good fits were obtained, but as expected this phase of the profile could not be modelled by either the single or double exponential functions. When the lag phase or post-convex curve data was removed from 20 data sets, use of the single exponential function resulted in three fits rated as excellent and two rated as good. When a double exponential model was applied to these data sets, three fits rated as good were obtained, whilst application of the modified Gompertz model gave one fit rated as good. The remainder of the fits were rated as moderate to fair. It is concluded that the evidence supporting the use of the single exponential model, the double exponential model or the non-logarithmic Gompertz model to describe full substrate degradation profiles in composting following their adjustment for temperature effects is limited. Further work is suggested in order to investigate the nature of those profiles which were not well modelled, to more precisely ascertain the cardinal temperatures for composting used in the function of Rosso et al. (1993) [Rosso, L., Lobry, J.R., Flandrois, J.P., 1993. An unexpected correlation between cardinal temperatures of microbial growth highlighted by a new model. J. Theor. Biol 162, 447-463.], which was employed in the present temperature correction procedure, and to incorporate correction for varying moisture and oxygen concentrations. PMID- 17855071 TI - Ultrasensitive DNA hybridization biosensor based on polyaniline. AB - Ultrasensitive DNA hybridization biosensor based on polyaniline (PANI) electrochemically deposited onto Pt disc electrode has been fabricated using biotin-avidin as indirect coupling agent to immobilize single-stranded 5'-biotin end-labeled polydeoxycytidine (BdC) probes and 5'-biotin end-labeled 35 base-long oligonucleotide probe (BdE) to detect complementary target, using both direct electrochemical oxidation of guanine and redox electroactive indicator methylene blue (MB), respectively. These polyaniline-based disc electrodes have been characterized using differential pulse voltammetry (DPV), Fourier transform infrared spectroscopy (FT-IR), impedance measurements and scanning electron microscopy (SEM) techniques, respectively. Compared to direct electrochemical oxidation of guanine, hybridization detection using MB results in the enhanced detection limit by about 100 times. These DNA immobilized PANI electrodes have hybridization response time of about 60 s. PMID- 17855072 TI - Pain in oxaliplatin-induced neuropathy--sensitisation in the peripheral and central nociceptive system. AB - BACKGROUND: This study aimed to determine the somatosensory characteristics and pain types in patients with acute oxaliplatin-induced neuropathy and to relate this profile to the hereby detected underlying pathophysiological mechanisms. PATIENTS AND METHODS: Sixteen patients treated with oxaliplatin for cancer were characterised with neurological assessment and a standardised and validated set for quantitative sensory testing (QST). Patients were allocated to two groups depending on the presence or absence of pain symptoms of acute neuropathy. RESULTS: Comparison with normative data revealed in patients with pain symptoms a characteristic somatosensory profile of cold and mechanical hyperalgesia. Group to-group analysis revealed additional heat hyperalgesia and warm hypoesthesia. CONCLUSION: Pain symptoms of acute oxaliplatin-induced neuropathy are related to signs of sensitisation within the peripheral (cold and heat hyperalgesia) and central nervous nociceptive system (mechanical hyperalgesia). This strengthens the rationale for treatment with anticonvulsants and antidepressants and fosters research on ion channel and receptor related mechanisms. PMID- 17855073 TI - Contribution of the geriatrician to the management of cancer in older patients. AB - With an increasingly aged population, many patients will present with cancer in their 80s and 90s. Although some may be very fit, frail individuals will require the input of geriatricians to aid in the assessment of co-existing morbidity, in an attempt to assess those most likely to benefit from active treatment of their cancer, and those in whom the 'giants of geriatric medicine' require special consideration before undergoing definitive cancer therapy. The role of the geriatrician in assessment and management of such patients, together with communication and end of life care, may be more important in ensuring a good quality of life, than the cancer therapy itself. Whilst numbers of geriatricians will not be adequate to care for all elderly patients with cancer, a variety of assessment scales will help target financial and manpower resources to those most at risk. PMID- 17855074 TI - Comprehensive geriatric assessment and its clinical impact in oncology. AB - Comprehensive geriatric assessment (CGA) is a process that consists of a multidimensional data-search and a process of analyzing and linking patient characteristics creating an individualized intervention-plan, carried out by a multidisciplinary team. In general, the positive health care effects of CGA are established, but in oncology both CGA and the presence of geriatric syndromes still have to be implemented to tailor oncological therapies to the needs of elderly cancer patients. In this paper the conceptualization of geriatric syndromes, their relationship to CGA and results of clinical studies using CGA in oncology are summarized. Geriatric syndromes are associated with increased vulnerability and refer to highly prevalent, mostly single symptom states (falls, incontinence, cognitive impairment, dizziness, immobility or syncope). Multifactorial analysis is common in geriatric syndromes and forms part of the theoretical foundation for using CGA. In oncology patients, we reviewed the value of CGA on the following endpoints: recognition of health problems, tolerance to chemotherapy and survival. Most studies performed CGA to identify prognostic factors and did not include an intervention. The ability of CGA to detect relevant health problems in an elderly population is reported consistently but no randomized studies are available. CGA should explore the pre-treatment presence of (in)dependence in Instrumental Activities of Daily Living (IADL), poor or moderately poor quality of life, depressive symptoms and cognitive decline, and thereby may help to predict survival. However, if scored by the Charlson comorbidity-index, comorbidities are not convincingly related to survival. The few studies that included a CGA-linked intervention show inconsistent results with regard to survival but compared to usual care quality of life is improved in the surviving period. Functional performance scores and dependency at home appeared to be independent predictive factors for toxicity, similar to depressive symptoms and polypharmacy. Overall, CGA implements/collects information additional to chronological age and Performance Score. So far in oncology there are no prognostic validation studies reported using geriatric syndromes or information based on CGA in its decision making strategies. PMID- 17855075 TI - HER2 status in early breast cancer: relevance of cell staining patterns, gene amplification and polysomy 17. AB - The prevalence of HER2 amplification according to the percentage of positively stained cells, of polysomy 17 and their correlation with clinical and pathologic characteristics were retrospectively evaluated in a population of 415 breast cancers where fluorescence in situ hybridisation (FISH) was performed to clarify HER2 status previously determined by immunohistochemistry. Forty-two tumours with intense and complete staining in >50% of cells were selected from the same database as internal controls. Among the 415 cases, 233 tumours were IHC 1+, 168 tumours were 2+ and 14 tumours showed an intense and complete immunostaining in 50% of neoplastic cells. HER2 was amplified in 3/14 (21.4%) tumours with 50% and in 36/42 (85.7%) tumours with >50% of intense stained cells, (p<0.001). Polysomy 17 was detected in 77 tumours (16.85%). It was inversely correlated with the percentage of positively stained cells, but not with amplification. Patients with polysomy 17 and no amplification were significantly more likely to have tumours with favourable biological features when compared with patients with HER2 amplification. Our results suggest that FISH testing should be considered for tumours with 50% positive stained cells and that polysomy 17 without amplification is not associated with poor prognostic features. PMID- 17855076 TI - Palliative care for patients with advanced pancreatic and biliary cancers. AB - Because most patients with pancreatic and biliary cancer have advanced disease, the palliation of debilitating symptoms is critically important in patient management. A multidisciplinary team consisting of representatives from surgery, medical oncology, gastroenterology, radiology, and palliative care medicine is essential for the optimal palliation of symptoms. In this article, the key issues in palliative care for patients with advanced pancreatic and biliary cancer are discussed. In particular, the prevention and amelioration of suffering due to obstructive jaundice, gastric outlet obstruction, cancer-related pain, pancreatic enzyme insufficiency, and thromboembolic disease is addressed. To this end, an algorithm for the multidisciplinary management of these challenging patients is proposed with the goal of providing clinicians with a useful framework for providing palliative care for patients with advanced pancreatic and biliary cancer. PMID- 17855077 TI - Palliation of advanced thyroid malignancies. AB - While most thyroid cancers are slow-growing and have an excellent prognosis after appropriate treatment, a subset of thyroid cancers behave aggressively, and approximately 1500 individuals in the US will die of the disease in the year 2007. Advanced thyroid malignancies can cause distressing and life-threatening symptoms by local invasion in the neck, growth of distant metastases in the lung, bone, and other organs, and tumor production of bioactive substances in the case of medullary thyroid cancer. This article will review palliative modalities, including surgery, radioactive iodine, external beam radiation, and chemotherapy, as well as novel targeted therapies, for the treatment of patients with advanced thyroid malignancies. PMID- 17855078 TI - Impact of pedicle clamping in pediatric liver resection. AB - BACKGROUND: Vascular clamping techniques are commonly used but so far the impact on pediatric liver surgery has not been investigated. The purpose of this study was to analyze pedicle clamping during pediatric liver resection in terms of hepato-cellular injury and blood loss. METHODS: Sixty-seven children undergoing liver resection were analyzed retrospectively. Vascular clamping was used in 28 cases (PC group), in 39 the resection was performed without clamping (NPC group). Major hepatectomies (resection of more than three segments) were carried out in 88%, minor hepatectomies (resection of three and less segments) in 12% of patients. Twenty-six children underwent extended liver resection. Patient data, liver function tests (LFTs) and blood loss were analyzed statistically. RESULTS: There were no significant differences in patient preoperative and postoperative data and LFTs between the groups. Within the NPC group the amount of administered fresh frozen plasma (FFP) in total and per kilogram (FFP/kg) was significantly higher (p=0.023 and 0.028) than in the PC group. For patients with extended liver resection, operation times were significantly longer (p=0.016) in the group without vascular clamping (NPCext). In the NPCext group significantly more children required packed red cells, FFP and FFP/kg. LFTs showed no significant differences in all children regardless of vascular clamping. CONCLUSIONS: For children undergoing liver resection, vascular clamping offers a blood saving surgical technique. Postoperative LFTs were not statistically different, regardless of vascular clamping. Pedicle clamping proved to be a safe method, not associated with an increase in perioperative complications. PMID- 17855079 TI - Solid state microcellular foamed poly(lactic acid): morphology and property characterization. AB - Poly(lactic acid) or PLA is a plant-based biodegrable plastic which exhibits many properties that are equivalent to or better than many petroleum-based plastics. However, there have been few commercial applications due to its lower impact resistance and higher cost than synthetic plastics. In this paper, the concept of creating microcellular foamed structures in PLA as a means to improve its shortcomings is presented. The effect of the foaming conditions (temperature and time) on the void fraction, volume expansion ratio, impact strength and tensile properties of foamed PLA is discussed. Each step of microcellular processing is addressed including: the manufacture of PLA film; the saturation of the samples with gas; the microcellular foaming of PLA; the void fraction determination, volume expansion ratio calculation, impact and tensile property characterization of foamed samples. The microcellular morphologies developed in PLA samples were a strong function of the foaming conditions. Due to the presence of foamed microcells, a twofold expansion ratio and significant improvements in the impact resistance (twofold increase over unfoamed PLA), strain at break (up to twofold increase over unfoamed PLA) and toughness (up to fourfold increase over unfoamed PLA) were achieved in PLA. PMID- 17855080 TI - Biosorption of Malachite Green from aqueous solutions onto aerobic granules: kinetic and equilibrium studies. AB - Batch experiments were conducted to study the biosorption characteristics of a cationic dye, Malachite Green (MG), onto aerobic granules. Effects of pH, aerobic granule dosage, contact time and solution temperature on MG biosorption by aerobic granules were evaluated. Simultaneity the thermodynamic analysis was also performed. The results showed that alkaline pH was favorable for the biosorption of MG and chemisorption seemed to play a major role in the biosorption process. Kinetic studies indicate that MG biosorption on aerobic granules in the system follows the pseudo-second order kinetics. The equilibrium time was 60 min for both 50 and 60 mg/L and 120 min for both 70 and 80 mg/L MG concentrations, respectively. Moreover, the experimental equilibrium data have been analyzed using the linearized forms of Langmuir, Freundlich, and Redlich-Peterson isotherms and the Langmuir isotherm was found to provide the best theoretical correlation of the experimental data for the biosorption of MG. The monolayer biosorption (saturation) capacities were determined to be 56.8 mg of MG per gram of aerobic granules at 30 degrees C. Thermodynamic analysis show that biosorption follows an endothermic path of the positive value of Delta H( composite function) and spontaneous with negative value of Delta G( composite function). PMID- 17855081 TI - Production of trans-2-methyl-5-isopropylhexa-2,5-dienoic acid by Pseudomonas rhodesiae CIP 107491. AB - The feasibility of trans-2-methyl-5-isopropylhexa-2,5-dienoic acid (novalic acid) accumulation using the alpha-pinene degradation pathway of Pseudomonas rhodesiae CIP 107491 was studied. This appeared possible by using concentrated living bacterial cells produced under oxygen limitation with alpha-pinene as sole carbon source. The second step of the process, the bioconversion itself, had to be performed without oxygen limitation due to the need for cofactor regeneration. Results showed that a not yet reported cofactor-dependent enzymatic isomerization of isonovalal into novalal was likely to occur and that both aldehyde isomers could be oxidized to the corresponding acid. Precursors tested, alpha-pinene oxide and isonovalal had a strong permeabilization effect on bacterial cells. This effect, which increased from the oxide to the aldehyde, led to an inactivation of the respiratory chain and to acids synthesis stop. Present results allowed to obtain about 12 g/L acids (80% novalic acid) with an average yield close to 50% after 12h reaction in a biphasic system using alpha-pinene oxide as precursor . PMID- 17855082 TI - Equilibrium isotherm studies for the uptake of cadmium and lead ions onto sugar beet pulp. AB - The adsorption of Cd2+ and Pb2+ on sugar beet pulp (SBP), a low-cost material, has been studied. In the present work, the abilities of native (SBP) to remove cadmium (Cd2+) and lead (Pb2+) ions from aqueous solutions were compared. The (SBP) an industrial by product and solid waste of sugar industry were used for the removal of Cd2+ and Pb2+ ions from aqueous water. Batch adsorption studies were carried out to examine the influence of various parameters such as initial pH, adsorbent dose, initial metal ion concentration, and time on uptake. The sorption process was relatively fast and equilibrium was reached after about 70 min of contact. As much as 70-75% removal of Cd2+ and Pb2+ ions for (SBP) are possible in about 70 min, respectively, under the batch test conditions. Uptake of Cd2+ and Pb2+ ions on (SBP) showed a pH-dependent profile. The overall uptake for the (SBP) is at a maximum at pH 5.3 and gives up to 46.1 mg g(-1) for Cd2+ and at pH 5.0 and gives 43.5 mg g(-1) for Pb2+ for (SBP), which seems to be removed exclusively by ion exchange, physical sorption and chelation. A dose of 8 gL(-1) was sufficient for the optimum removal of both the metal ions. The Freundlich represented the sorption data for (SBP). In the presence of 0.1M NaNO3 the level of metal ion uptake was found to reach its maximum value very rapidly with the speed increasing both with the (SPB) concentration and with increasing initial pH of the suspension. The reversibility of the process was investigated. The desorption of Cd2+ and Pb2+ ions which were previously deposited on the (SBP) back into the deionised water was observed only in acidic pH values during one day study period and was generally rather low. The extent of adsorption for both metals increased along with an increase of the (SBP) dosage. (SBP), which is cheap and highly selective, therefore seems to be a promising substrate to entrap heavy metals in aqueous solutions. PMID- 17855083 TI - Production of biosurfactant and antifungal compound by fermented food isolate Bacillus subtilis 20B. AB - A biosurfactant producing strain, Bacillus subtilis 20B, was isolated from fermented food in India. The strain also showed inhibition of various fungi in in vitro experiments on Potato Dextrose Agar medium. It was capable of growth at temperature 55 degrees C and salts up to 7%. It utilized different sugars, alcohols, hydrocarbons and oil as a carbon source, with preference for sugars. In glucose based minimal medium it produced biosurfactant which reduced surface tension to 29.5 mN/m, interfacial tension to 4.5 mN/m and gave stable emulsion with crude oil and n-hexadecane. The biosurfactant activity was stable at high temperature, a wide range of pH and salt concentrations for five days. Oil displacement experiments using biosurfactant containing broth in sand pack columns with crude oil showed 30.22% recovery. The possible application of organism as biocontrol agent and use of biosurfactant in microbial enhanced oil recovery (MEOR) is discussed. PMID- 17855084 TI - Restart of anaerobic filters treating low-strength wastewater. AB - The anaerobic filter (AF) technology offers an alternative method for the direct treatment of low-strength wastewater and the study was undertaken to access AF biomass reactivation after prolonged nonfeeding periods, an important characteristic making the process suitable for handling variable or intermittent pollution loads. Four upflow AF (three 12.5-L and one 3.9-L, each with different packing), which had treated municipal-type wastewaters (natural, amended or synthetic) for 34 months at 25 or 16 degrees C and varying hydraulic loads and had remained inactive for 24 months, were used. All units were fed synthetic wastewater [mean chemical oxygen demand (COD) 323 mg/L, total suspended solids (TSS) 47 mg/L] and operated at 27 degrees C for 2.5 months (phase 1); and following a 6-month idle period, the smaller filter treated municipal wastewater (mean COD and TSS 820 and 448 mg/L) at 16 degrees C for an additional 2.5 months (phase 2). The larger units operated at a 2.0-d hydraulic retention time and the smaller at 1.0-0.33-d in phase 1 and 2.0 or 1.0-d in phase 2. Reactivation was quick and yielded efficient treatment. Restart was affected by the AF history and packing morphology, the types of wastewater previously handled, and the duration of the nonfeeding period. PMID- 17855085 TI - Single-stage, batch, leach-bed, thermophilic anaerobic digestion of spent sugar beet pulp. AB - Spent sugar beet pulp as received was digested in a single-stage, batch, unmixed, leach-bed, laboratory scale thermophilic anaerobic digester. Biogasification of each 0.450 kg (wet weight) batch of spent pulp was initiated by inoculating with anaerobically digested liquor from previous run. The average methane yield was 0.336 m3 CH4 at STP (kgVS)(-1), the maximum methane production rate was 0.087 m3 CH4 at STP (kgVS)(-1)d(-1), average lag time to initiate methanogenesis was only 0.44 days and time required to achieve 95% methane yield was 8 days. The pH in the digesters ranged between 8.0 and 9.5. High rates of methane generation were sustained even at high pH values. The equivalent organic loading rate in the batch digesters was 4 kgCODm(-3)d(-1). The digestion process used here offers significant improvements over one-stage and two-stage systems reported in the literature with comparable performance as it is a single-stage system where the feedstock does not require size reduction, and mixing is not required in the digester. PMID- 17855086 TI - NO donors. Part 16: investigations on structure-activity relationships of organic mononitrates reveal 2-nitrooxyethylammoniumnitrate as a high potent vasodilator. AB - The vasoactive properties of 14 organic mononitrates were investigated in vitro using PGF(2alpha)-precontracted porcine pulmonary arteries. A surprisingly wide range of vasorelaxant potencies was observed (pD(2): 3.36-7.50). Activities showed to be highly sensitive to the molecular structure and the substituents at the molecular carrier of the nitrate group. A correlation between lipophilicity and vasorelaxant potency could not be recognized. 2-Nitrooxyethylammoniumnitrate (1) was found to be slightly superior to the high potency trinitrate GTN. PMID- 17855087 TI - Identification and synthesis of major metabolites of Vasopressin V2-receptor agonist WAY-151932, and antagonist, Lixivaptan. AB - Small molecule agonists and antagonists of the V(2)-vasopressin receptor have been discovered and have undergone clinical trials. In conjunction with these discovery programs, the synthesis and biological testing of various metabolites associated with these clinical targets were actively pursued. We now report the results of our synthetic efforts and the corresponding biological data generated for several of the metabolites of WAY-151932 and CL-347985 (Lixivaptan). PMID- 17855088 TI - Design and evaluation of analogues of the bacterial cell-wall peptidoglycan motif L-Lys-D-Ala-D-Ala for use in a vancomycin biosensor. AB - Four small molecular receptors of vancomycin have been designed to make part of a novel biosensor device based on the FTIR-ATR detection: N-Boc (2a) or N-Ac (2b)-6 aminocaproyl-D-Ala-D-Ala and N-Boc (3a) or N-Ac (3b)-6-aminocaproyl-D-Ala-d-Ser. Using an original microbiological approach to assess the competition of compounds with the natural target of vancomycin in bacteria, EC(50) values of 6.3-8.0 x 10( 5)M (2a-b) and 7.1-9.3 x 10(-4)M (3a-b) were determined. Vancomycin:2b complex was characterized by MS. PMID- 17855089 TI - Amino(methyl) pyrrolidines as novel scaffolds for factor Xa inhibitors. AB - The design and synthesis of a novel class of amino(methyl) pyrrolidine-based sulfonamides as potent and selective FXa inhibitors is reported. The amino(methyl) pyrrolidine scaffolds were designed based on the proposed bioisosterism to the piperazine core in known FXa inhibitors. The SAR study led to compound 15 as the most potent FXa inhibitor in this series, with an IC(50) of 5.5 nM and PT EC(2x) of 1.7 microM. The proposed binding models show that the pyrrolidine cores are in van der Waals contact with the enzyme surface, and the flexibility of amino(methyl) pyrrolidines allows the two nitrogen atoms to anchor both the P1 and P4 groups to fit similarly in the S1 and S4 pockets. PMID- 17855090 TI - Studies on the interactions between some flavonols and cyclodextrins. AB - The interactions of some natural flavonols with alpha, beta- and gamma-Cds have been investigated. Guest molecules were galangin, kaempferol and quercetin. Inclusion complexes were prepared by kneading and freeze-drying. The complexes were characterized using different physico-chemical methods based on differential scanning calorimetry (DSC), infrared spectroscopy (IR) and NMR spectroscopy. In the proton and carbon spectra the effects of complexation on the chemical shifts of the internal and external protons of Cds in the presence of each flavonoid were observed. Moreover, the water-solubility of the flavonols in the presence of Cds was also evaluated. The increased solubility of quercetin and kaempferol in the presence of beta-Cd was evidenced. For all three guests, multidimensional NMR experiments in DMSO and water are consistent with dynamic binding processes, dominated by insertion of the B ring into the wider rim of the Cd cavity. PMID- 17855091 TI - Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitors. AB - Structure-based design, synthesis, and biological evaluation of a series of peptidomimetic severe acute respiratory syndrome-coronavirus chymotrypsin-like protease inhibitors are described. These inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 1 bound to SARS-CoV 3CLpro. Incorporation of Boc-Ser as the P(4)-ligand resulted in enhanced SARS-CoV 3CLpro inhibitory activity. Structural analysis of the inhibitor-bound X-ray structure revealed high binding affinity toward the enzyme. PMID- 17855092 TI - Synthesis and identification of novel 11beta-aryl-4',5'-dihydrospiro[estra-4,9 diene-17beta,4'-oxazole] analogs with dissociated antiprogesterone activities. AB - A series of novel 11beta-aryl-4',5'-dihydrospiro[estra-4,9-diene-17beta,4' oxazole] analogs have been evaluated for their antagonist hormonal properties using the T47D cell-based alkaline phosphatase assay and the A549 cell-based functional assay. Some of the compounds showed highly potent, and more selective antiprogestational activity against antiglucocorticoid activity than mifepristone (RU 486). PMID- 17855093 TI - Effect of indole ethyl isothiocyanates on proliferation, apoptosis, and MAPK signaling in neuroblastoma cell lines. AB - Several indole ethyl isothiocyanate (IEITC) analogs were designed, synthesized, and screened to evaluate their cytotoxicity against neuroblastoma (NB) cells in vitro. In NB, predominantly a tumor of early childhood, survival remains low despite aggressive treatments. Therefore, novel treatment strategies are greatly needed. The objective of the present study was to study the therapeutic potential of IEITC by analyzing the cytotoxic, anti-proliferative, and apoptotic effects on NB cell lines. 7-Methyl-indole-3-ethyl isothiocyanate (7Me-IEITC) proved to be cytotoxic to various NB cell lines (SMS-KCNR, SK-N-SH, SH-SY5Y, and IMR-32) with an IC(50) at 2.5-5.0 microM, while primary control cells (lung fibroblasts) were not affected. 7Me-IEITC led to the activation of apoptotic markers caspase-3, -8, and -9, caused activation of pro-apoptotic p38 MAPK and SAP/JNK, and down regulated pro-survival factor AKT in SMS-KCNR cells. Moreover, 7Me-IEITC displayed anti-proliferative effects (IC(50) at 600 nM) and caused an arrest in cell cycle progression. This wide effect of 7Me-IEITC on NB cell signaling and survival suggests that it could be developed as a therapeutic agent against neuroblastoma. PMID- 17855094 TI - Ascertainment of breast cancer by the Scottish Cancer Registry: an assessment based on comparison with five independent breast cancer trials databases. AB - Completeness of ascertainment of breast cancer cases by the Scottish Cancer Registry (SCR) was assessed by independent comparison with five clinical trials databases, comprising 2621 patients and spanning the total period of diagnosis 1978-2000. Overall, ascertainment was estimated to exceed 98%, although 0.3% of matched cases were misclassified as carcinoma in situ by the SCR. These results support the validity of national estimates of incidence of, and survival from, breast cancer in Scotland. PMID- 17855095 TI - Protocol changes can improve the reliability of net oxygen cost data. AB - There are concerns that experimental imprecision of measured oxygen cost reduces its clinical utility. These concerns are exacerbated when net energy (walking resting) is assessed. Therefore, the variability of net oxygen cost should be carefully evaluated, including an exploration of the potential for protocol changes to improve the measure's reliability. In this study a retrospective analysis was used to compare the variability in net oxygen cost between two protocols at a single center. Two groups of subjects (protocols) were analyzed. The subjects in each group met the following criteria: (i) diagnosis of cerebral palsy, (ii) no prior surgery, and (iii) oxygen cost data collected while walking barefoot. The protocols differed in terms of subject preparation, duration of the resting period, and the method used for determining both resting and walking steady state. The net non-dimensional oxygen cost versus dimensionless speed showed essentially identical quadratic regression fits for the two groups, suggesting that the samples were well matched, and the protocols were unbiased. The variability, as measured by mean square error, showed an approximately five fold reduction with respect to the regression (MSE(old)=.262, MSE(new)=.050), indicating a significant decrease in experimental errors. Further analysis is warranted to determine the primary sources of error reduction, and to further optimize the testing protocol. PMID- 17855096 TI - Recovery of muscle strength following multi-level orthopaedic surgery in diplegic cerebral palsy. AB - Muscle strength changes following multi-level surgery in cerebral palsy and the impact of rehabilitation on functional recovery are largely unknown. The aim of this study was to quantify lower limb muscle strength changes in children with spastic diplegia after multi-level orthopaedic surgery and to compare the efficacy of progressive resistance strengthening (RS) versus active exercise (AE). Twenty children with spastic diplegia (mean age 12.5 years) participated in this prospective randomised controlled trial. Participants underwent multi-level orthopaedic surgery. Routine physiotherapy commenced immediately after surgery. At 6 months post-operatively, children were randomly assigned to the resistance strengthening RS (n=11) or active exercise AE (n=9) group and received intensive physiotherapy for 6 weeks. Gait, motor function and maximum isometric muscle strength in five lower limb muscle groups were measured pre-operatively and at 6 months (before and after intensive physiotherapy) and 12 months. As part of the study, we developed and validated a myometry protocol. Despite kinematic improvements, there was significant reduction of muscle strength (p<0.05) in all muscle groups at 6 months post-operatively. Following 6 weeks of intensive physiotherapy, both groups showed significant improvement in muscle strength, GMFM scores and gait parameters. Resistance training showed some advantages over active exercise. At 1 year after surgery, strength did not reach pre-operative values in some muscle groups but the benefit from physiotherapy was maintained. In conclusion, we quantified objectively the reduction in muscle strength 6 and 12 months following multi-level surgery. Furthermore, we demonstrated significant improvement in muscle strength, gait and function following post-operative strength training. PMID- 17855097 TI - Significance of chirality in pheromone science. AB - Pheromones play important roles in chemical communication among organisms. Various chiral and non-racemic pheromones have been identified since the late 1960s. Their enantioselective syntheses could establish the absolute configuration of the naturally occurring pheromones and clarified the relationships between absolute configuration and bioactivity. For example, neither the (R)- nor (S)-enantiomer of sulcatol, the aggregation pheromone of an ambrosia beetle Gnathotrichus sulcatus, is behaviorally active, while their mixture is bioactive. In the case of olean, the olive fruit fly pheromone, its (R)-isomer is active for the males, and the (S)-isomer is active for the females. About 140 chiral pheromones are reviewed with regard to their stereochemistry bioactivity relationships. Problems encountered in studying chirality of pheromones were examined and analyzed to think about possible future directions in pheromone science. PMID- 17855098 TI - Direct diazo-transfer reaction on beta-lactam: synthesis and preliminary biological activities of 6-triazolylpenicillanic acids. AB - In this study we report the first example of a direct diazo-transfer reaction on readily available 6-aminopenicillanates to give 6-azidopenicillanates in high yield. Subsequent Cu(I)-catalyzed Huisgen cycloaddition between these 6 azidopenicillanates and assorted terminal alkynes facilely furnished 6 triazolylpenicillanic acids. Preliminary biological screening indicates that these triazolylpenicillanic acids possess low to moderate antibacterial activities. PMID- 17855099 TI - Radionuclide calibrator comparisons and quality improvement in nuclear medicine. AB - The traceability of activity measurements performed during the development phase of the radiopharmaceutical and in its clinical application is essential for establishing the comparability of clinical results reported in the nuclear medicine field. This paper presents and discusses the evaluation over time of the quality of activity measurement results obtained in Cuban nuclear medicine, on the basis of statistical samples taken during the radionuclide calibrator comparison program. An attempt is also made to evaluate the role played by such comparisons in quality measurement improvement in nuclear medicine, on the basis of results obtained in a number of countries and published by several authors over a period of time. Specifically, improvements of the measurement performance over time assessed by such exercises were found dissimilar in magnitudes for different countries. Two phases could be distinguished in the improvement process over time. Firstly, a fast improvement can be obtained resulting from the improvement in measurement accuracy of devices. After that, the achievement of new and sustained improvements goes slowly and requires an application of quality assurance programs where the qualification upgrading of personnel become an essential point. PMID- 17855100 TI - Fissile material detection using a prompt fission neutron chamber system. AB - The calculations supporting the design of a chamber system to detect and verify fissile material in items such as mail packages or luggage are described. Stimulated neutrons from fission are separated from those produced by the system 14 MeV neutron generators by time delay. The proposed system design has a chamber volume of 60x60x90 cm. It is anticipated that at least 1g of fissile material could be detected in as little as 5s of interrogation. PMID- 17855101 TI - Ratio of tritiated water and hydrogen generated in mercury through a nuclear reaction. AB - Tritium generated in a mercury target is a source of potential exposure of personnel at high-energy accelerator facilities. Knowledge of the chemical form of tritium is necessary to estimate the internal doses. We studied the tritium generation upon thermal neutron irradiation of a mercury target modified into liquid lithium amalgam to examine the ratio of tritiated water ([3H]H2O) and tritiated hydrogen ([3H]H2). The ratio between [3H]H2O and [3H]H2 generated in lithium amalgam was 4:6 under these experimental conditions. PMID- 17855102 TI - Single-acquisition method for simultaneous determination of extrinsic gamma camera sensitivity and spatial resolution. AB - A new method for measuring simultaneously both the extrinsic sensitivity and spatial resolution of a gamma-camera in a single planar acquisition was implemented. A dual-purpose phantom (SR phantom; sensitivity/resolution) was developed, tested and the results compared with other conventional methods used for separate determination of these two important image quality parameters. The SR phantom yielded reproducible and accurate results, allowing an immediate visual inspection of the spatial resolution as well as the quantitative determination of the contrast for six different spatial frequencies. It also proved to be useful in the estimation of the modulation transfer function (MTF) of the image formation collimator/detector system at six different frequencies and can be used to estimate the spatial resolution as function of the direction relative to the digital matrix of the detector. PMID- 17855103 TI - Postoperative complications in 202 cases of microvascular head and neck reconstruction. AB - INTRODUCTION: This retrospective study was intended to determine the incidence and causes of postoperative complications in patients following head and neck reconstruction using microvascular free flaps. PATIENTS AND METHODS: A total of 202 consecutive microvascular free flaps were performed for reconstruction of the head and neck by the same surgeon, 85% of the defects arose following the treatment of malignancies. Flap donor sites included latissimus-dorsi flap (n=83), radial forearm (n=35), fibula (n=31), iliac crest (n=36), TRAM flap (n=3), groin flap (n=l), jejunal flap (n=13). The incidence of postoperative complications and patient-related characteristics (age, sex, diagnosis, comorbidity level, operation duration, defect site, history of radiotherapy/chemotherapy) were retrospectively analyzed. RESULTS: Free flaps proved to be extremely reliable, with a 2.9% incidence of free flap failure. Postoperative medical complications occurred in 11.4% of cases, with cardiac, pulmonary and infectious complications predominating. CONCLUSION: The present study confirms that free flaps are extremely reliable in achieving successful reconstruction of the head and neck. The incidence of postoperative complications is related to the preoperative comorbidity. PMID- 17855104 TI - Ectopic bone formation as a complication of surgical rehabilitation in patients with Moebius' syndrome. AB - PURPOSE: Treatment of facial paralysis by muscular neurotization resulted in ectopic ossification in 1 of 134 cases in this department. That patient suffering from Moebius syndrome (MS) is presented. Reviewing the literature concerning MS, Hox genes and bone morphogenetic protein dysregulation, a pathogenesis of ossification in MS is suggested. PATIENT: The MS patient exhibited a congenital facial nerve palsy, which was treated by muscular neurotization (Lexer Rosenthal). Because of postoperative ossification of scarred areas, osteotomy of the processus muscularis and mobilization of the masseter muscle was performed. Nevertheless, further ossification occurred at the interface between the mandible and zygoma and in two masticatory muscles. So, the construction of a neoarthrosis became necessary. Three years later, the iatrogenic bone defect had reossified despite of an active opening therapy. CONCLUSIONS: Ectopic ossification after muscular neurotization seems to be restricted to patients with MS and is triggered by trauma. Molecular pathogenesis: facial malformations in MS are caused by disturbances in embryonic patterning. Failure in the development of the second pharyngeal arch leads to a spatial BMP-4 dysregulation responsible for ossification after wounding of muscle fascia. Therefore, surgical rehabilitation of facial function by muscular neurotization is contra indicated in MS patients. PMID- 17855105 TI - Bi-directional distraction in the treatment of micro-orbitism: a case report. AB - INTRODUCTION: Correction of micro-orbitism, resulting from clinical or congenital anophthalmia, has traditionally been performed by multiple segmentation of the orbital rim, orbital expanders and orbital conformers. Although distraction osteogenesis is a widely employed surgical approach in the treatment of patients with bony malformations, it has not been employed to enlarge micro-orbits. MATERIAL AND METHODS: The present article describes the development of a new bi directional orbital distractor to treat a 17-year-old patient affected by micro orbitism, caused by clinical anophthalmia. The deformity required an internal device to expand and to pull the orbit laterally. Surgical planning and device design were performed by means of patient-specific finite element analysis and a stereolithography model. The surgery consisted of a uni-lateral orbito-malar osteotomy performed via coronal and intraoral access. A 7-day-latency period was observed. The consolidation phase was chosen as six months. RESULTS: At the end of the distraction process, symmetry of the malar bones and orbital roofs was achieved. During removal of the device, newly formed bone was found at the original osteotomy and distraction gaps. CONCLUSION: The reported clinical case suggests that distraction osteogenesis can be a useful procedure for enlargement of micro-orbits. Despite this, a number of questions need to be addressed by long term follow-up and careful study of future cases. PMID- 17855106 TI - Appropriate diameter for screws to fix the maxilla following Le Fort I osteotomy: an investigation utilizing finite element analysis. AB - BACKGROUND: After Le Fort I osteotomy, there is sometimes a secondary deformity (relapse), with the lower segment deviating from the intraoperatively fixed position. It is hyopothesized that the structural stability of the reconstructed maxilla is affected by the diameter of the fixation screws. The present study aims to elucidate the relationship between the diameters of the screws and the structural stability of the maxilla after Le Fort I osteotomy. METHODS: 3D models were produced on a workstation from 20 dry skulls and a Le Fort I operation was simulated on them. The upper and lower segments of the divided maxilla in each of the 20 models were connected using four plates and 16 screws. Five different diameters of the fixation screws were tested. Thus altogether 100 models were produced. A 180N load was applied to the molar region for each model. Using finite element analysis, the resultant stresses and deviations of the lower segments were calculated. Finally, referring to these values, the relationships between screw diameters and stability of the lower segment were evaluated. RESULT: The stability of the lower segment was greatest when the diameter of the fixation screws was equal to the thickness of the bone at each fixation site. CONCLUSION: In performing Le Fort I osteotomy, it is recommended that bone thickness is measured at each fixation site in advance, and the diameter of the fixation screws matched accordingly; thereby optimum stability of the reconstructed maxilla can be anticipated. PMID- 17855107 TI - Evaluation of UV-C induced changes in Escherichia coli DNA using repetitive extragenic palindromic-polymerase chain reaction (REP-PCR). AB - Ultraviolet radiation is an efficient inactivation method for a broad range of bacteria, viruses and parasites. Inactivation of microorganisms by UV-B and UV-C radiation is driven through modifications in their genomic DNA, being the most stable DNA-lesions different kinds of pyrimidine dimers (PDs) (e.g., cyclobutane pyrimidine dimers (CPDs) and other photoproducts). Taking into account that these modifications inhibit the DNA polymerization in vivo as well as in vitro, in the present work the usefulness of the REP-PCR assay to detect UV-induced changes in the Escherichia coli DNA was evaluated. In vitro amplification of DNA extracted at different times after UV treatment showed a disappearance of amplicons of higher size as time of treatment increases. When the bacteria were let to progress through their dark repair process, modifications in the electrophoretic patterns by REP-PCR were observed again. Amplified bacterial DNA tended to recover the profile showed at the beginning of treatment. In addition, the reappearance of bands of higher molecular size was associated to an increase in their signal intensity probably due to a higher amplification rate. Results of REP-PCR were correlated to the colony-forming ability of E. coli. It was concluded that REP-PCR appears as a rapid, robust, useful complementary methodology to monitor the impact of UV irradiation--at a molecular level--on the inactivation and the mechanisms of repair, applicable on a broad spectrum of microorganisms. PMID- 17855108 TI - Pathophysiology, risk factors and management of bisphosphonate-associated osteonecrosis of the jaw: Is there a diverse relationship of amino- and non aminobisphosphonates? AB - Reports of osteonecrosis of the jaw (ONJ) in patients receiving long-term bisphosphonate therapy have appeared in the literature since 2003. This condition involves avascular necrotic bone in the area of maxilla or mandibula and there may be a secondary infection. Most cases of ONJ have been reported in cancer patients receiving the intravenous aminobisphosphonates zoledronic acid and pamidronate monthly or q 3 week; of note these are also the two most commonly used agents of this class. Risk factors for ONJ include a history of trauma, dental surgery or dental infection and intravenous bisphosphonate administration; in addition, the extent and duration of exposure to bisphosphonates also seem to correlate with the risk. Although a direct causal relationship with bisphosphonates cannot be assumed, these agents may possibly contribute to the development of ONJ by suppression of bone remodeling in the jaw which leads to increased rates of bone mineralisation and accumulation of microfractures. Clodronate, a non-aminobisphosphonate, appears to have a different mechanism of suppressing bone remodeling compared with aminobisphosphonates, and this may explain why few cases of ONJ have been reported with clodronate despite extensive use over the past 20 years; however, the potential of clodronate to reduce the risk of ONJ while providing equivalent clinical benefit to the aminobisphosphonates needs to be substantiated in controlled clinical trials. Use of bisphosphonate therapy should be carefully planned in patients with metastatic bone disease who have risk factors for ONJ, and appropriate preventive measures taken to avoid the development of this condition. PMID- 17855109 TI - Adipose stress-sensing kinases: linking obesity to malfunction. AB - Obesity has been proposed to inflict a variety of stresses on adipose tissue, including inflammatory, metabolic, oxidative and endoplasmic reticulum stress. Through the activation of 'stress-sensing pathways', metabolic and endocrine alterations are produced, which probably contribute to the co-morbidities associated with obesity. Here, we review the evidence supporting the development of various obesity-related stresses and the activation of several stress-sensing pathways, specifically in adipocytes and/or adipose tissue, which manifest metabolic and endocrine dysfunction frequently in obesity. As the central role of adipose tissue in regulating whole-body metabolism is elucidated, understanding adipose tissue stress-sensing pathways might provide potential new therapeutic targets to attenuate obesity-related morbidity. PMID- 17855110 TI - Quercetin 3-O-beta-(2''-galloyl)-glucopyranoside inhibits endotoxin LPS-induced IL-6 expression and NF-kappa B activation in macrophages. AB - We previously isolated quercetin 3-O-beta-(2''-galloyl)-glucopyranoside (QG-32) from Persicaria lapathifolia (Polygonacease) as an inhibitor of superoxide production. In the present study, QG-32 was found to inhibit interleukin (IL)-6 production in endotoxin lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7. The QG-32 attenuated LPS-induced synthesis of IL-6 transcript but also inhibited IL-6 promoter activity, indicating that the compound could down regulate LPS-induced IL-6 expression at the transcription level. Since nuclear factor (NF)-kappaB has been evidenced to play a major mechanism in the LPS induced IL-6 expression, an effect of QG-32 on NF-kappaB activating pathway was further analyzed. QG-32 inhibited nuclear import as well as DNA binding activity of NF-kappaB complex and subsequently suppressed NF-kappaB transcriptional activity in LPS-stimulated macrophages. However, QG-32 affected neither LPS induced inhibitory kappaB (IkappaB) degradation nor IkappaB kinase (IKK) activation. In another experiment, QG-32 inhibited expression vector encoding NF kappaB p65 or p50-elicited IL-6 promoter activity. Taken together, QG-32 could inhibit NF-kappaB-dependent IL-6 expression, targeting nuclear translocation of NF-kappaB complex downstream IkappaB degradation. This mechanism of action would be different from that of quercetin, an aglycone of QG-32, targeting IKK upstream IkappaB degradation. Finally, this study could provide a pharmacological potential of QG-32 in the inflammatory disorders. PMID- 17855111 TI - Probing the mechanisms of an air amplifier using a LTQ-FT-ICR-MS and fluorescence spectroscopy. AB - We report the first quantitative assessment of electrosprayed droplet/ion focusing enabled by the use of a voltage-assisted air amplifier between an electrospray ionization emitter and a hybrid linear ion trap Fourier transform ion cyclotron resonance mass spectrometer (ESI-LTQ-FT-ICR-MS). A solution of fluorescent dye was electrosprayed with a stainless steel mesh screen placed in front of the MS inlet capillary acting as a gas-permeable imaging plate for fluorescence spectroscopy. Without use of the air amplifier, no detectable FT-ICR signal was observed, as well as no detectable fluorescence on the screen upon imaging using a fluorescence scanner. When the air amplifier was turned ON while electrospraying the fluorescent dye, FT-ICR mass spectra with high signal to noise ratio were obtained with an average ion injection time of 21 ms for an AGC target value of 5 x 10(5). Imaging of the screen using a fluorescence scanner produced a distinct spot of cross-sectional area approximately 33.5 mm(2) in front of the MS inlet capillary. These experimental results provide direct evidence of aerodynamic focusing of electrosprayed droplets/ions enabled by an air amplifier, resulting in improved electrospray droplet/ion capture efficiency and reduced ion injection time. A second set of experiments was carried out to explore whether the air amplifier assists in desolvation. By electrospraying a mix of quaternary amines, ratios of increasingly hydrophobic molecules were obtained. Observation of the solvophobic effect associated with electrospray ionization resulted in a higher abundance of the hydrophobic molecule. This bias was eliminated when the air amplifier was turned ON and a response indicative of the respective component concentrations of the molecules in the bulk solution was observed. PMID- 17855113 TI - Re: Hypothesis: oxidative stress score as a combined measure of pro-oxidant and antioxidant exposures. PMID- 17855116 TI - Epidemiologic methods developments: a look forward to the year 2032. AB - This article responds to a request by the Editors for a perspective on potential epidemiologic methods developments between now and the year 2032 when the American College of Epidemiology will have its 50th Annual Meeting. The response begins by describing the need for enhanced methods in epidemiologic research and goes on to suggest some approaches to satisfying such needs. The suggested approaches include the more extensive use of biomarkers for exposure assessment, the greater standardization of data analysis and reporting methods, and enhancement of the interplay between observational studies and randomized controlled trials. It is argued that a phased approach to epidemiologic hypothesis evaluation may often be needed, with hypotheses that are promising in observational studies subjected to controlled trials having well-selected intermediate outcomes. It is also argued that a multidisciplinary, coordinated community of scientists interested in disease risk estimation and disease prevention will be needed for epidemiologic research to fulfill its potential over the next 25 years. PMID- 17855114 TI - Relationship of alcohol consumption and type of alcoholic beverage consumed with plasma lipid levels: differences between Whites and African Americans of the ARIC study. AB - PURPOSE: Alcohol consumption has been shown to contribute to a favorable lipid profile, and most studies have reported a reduction in coronary heart disease risk with low-to-moderate consumption of alcohol that is generally attributed to the beneficial effects of alcohol on lipids. The influence of different types of alcoholic beverages on plasma lipid levels has been investigated to a lesser extent and in limited populations. METHODS: We investigated the effect of overall alcohol consumption, as well as the type of alcoholic beverage consumed, on multiple lipid measures in the large bi-ethnic population of the Atherosclerosis Risk in Communities study. RESULTS: We found both low-to-moderate and heavy alcohol consumption, regardless of the type of alcoholic beverage consumed, to result in significantly greater levels of high-density lipoprotein (HDL) cholesterol, HDL3 cholesterol, and apolipoprotein A-I in both white and African American males and females. Associations with other lipid measures contrasted between whites and African Americans, with greater levels of alcohol consumption resulting in significantly greater triglyceride levels in African Americans. CONCLUSIONS: Our results confirm previous studies associating alcohol consumption, regardless of beverage type, with greater HDL cholesterol levels, with additional consistent associations detected for the major HDL cholesterol density subfraction, HDL3 cholesterol, and the major HDL cholesterol structural apolipoprotein, apolipoprotein A-I. PMID- 17855117 TI - Prevalence of asthma and wheeze in relation to passive smoking in Japanese children. AB - PURPOSE: Evidence remains inconclusive as to whether environmental tobacco smoke is a risk factor for allergic disorders in childhood. The present large-scale cross-sectional study examined the relationship between passive smoking at home and the prevalence of allergic disorders in Japanese schoolchildren. METHODS: Study subjects were 23,044 children aged 6 to 15 years in Okinawa. Outcomes were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Adjustment was made for sex, age, region of residence, number of siblings, paternal and maternal history of asthma, atopic eczema, or allergic rhinitis, as well as paternal and maternal educational level. RESULTS: The prevalence of wheeze, asthma, atopic eczema, and allergic rhinoconjunctivitis in the previous 12 months was 10.7%, 7.6%, 6.8%, and 7.7%, respectively. Current heavy passive smoking and 7.0 or more pack-years of smoking in the household were independently related to an increased prevalence of wheeze and asthma, especially in children 6 to 10 years of age and children with a positive parental allergic history. There was no dose-response relationship between pack-years of smoking in the household and atopic eczema or allergic rhinoconjunctivitis. CONCLUSIONS: Our findings suggested that environmental tobacco smoke might be associated with an increased prevalence of wheeze and asthma in Japanese children. PMID- 17855118 TI - Smoking cessation in clinical trials and public health studies: a research ethical imperative. PMID- 17855119 TI - Birthweight of offspring and mortality of parents: the Jerusalem perinatal study cohort. AB - PURPOSE: We sought to examine the association between birthweight in offspring and mortality in their parents. Distinguishing between risks of outcomes in mothers from fathers potentially provides clues as to the relative roles of genetic versus nongenetic mechanisms underlying these associations. METHODS: We studied total and cause-specific mortality in a population-based cohort of 37,718 mothers and 38,002 fathers whose offspring were delivered in West Jerusalem during 1964-1976, after an average follow-up of 34.12 years. RESULTS: Hazard models controlling for sociodemographic and lifestyle characteristics indicated a U-shaped relationship between offspring's birthweight and overall mortality, deaths from coronary heart disease, circulatory and other non-neoplastic causes in their mothers. Greater rates of mortality from coronary heart disease were observed among mothers who gave birth to babies with low (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.40-3.25) and high birthweight (HR, 1.98; 95% CI, 1.36-2.88), as compared with mothers whose offspring weighed 2500-3999 g at birth. Adjustment for maternal pre-eclampsia slightly attenuated these results. Multivariate models indicated a negative linear relationship (HR, 0.95; 95% CI, 0.91-0.99) between offspring's birthweight and overall mortality in their fathers. Unlike the association in mothers, the relation was noted primarily with deaths from "other causes." CONCLUSIONS: Birthweight of offspring is associated with parental mortality although the relation differs for fathers and mothers. These findings broaden previous observations that intra-uterine events have long term consequences for adult health and support the need to explore genetic and/or environmental mechanisms underlying these associations. PMID- 17855120 TI - Space-time clustering analyses of occurrence of cerebral palsy in Northern England for births 1991 to 2003. AB - PURPOSE: The etiology of congenital cerebral palsy is unclear. Recent studies have suggested that maternal infection is involved. Indirect, but supportive, evidence for an infectious hypothesis would be provided by the finding of space time clustering. METHODS: We analyzed all 906 cases born during the period 1991 2003 using a population-based registry from Northern England. We applied the K function method for testing global space-time clustering and used residential addresses at the time of birth. The Knox method was used to determine the spatio temporal range over which global clustering occurred. Tests were repeated using nearest neighbor thresholds to allow for variable population density. Additionally, Kulldorff's scan statistic identified specific space-time clusters. RESULTS: There was statistically significant evidence of global space-time clustering (p (4)F(7/2)) and Dy(3+):MgLaLiSi(2)O(7) phosphors with lambda(exci)=385 nm ((6)H(15/2)- >(4)I(13/2)) have been analyzed. Emission mechanisms of these phosphors have also been explained. PMID- 17855162 TI - Comparative spectroscopic and electrochemical study of nitroindazoles: 3-alcoxy, 3-hydroxy and 3-oxo derivatives. AB - Cyclic voltammetry and electron spin resonance techniques were used in the investigation of novel 3-alkoxy- and 3-hydroxy-1-[omega-(dialkylamino)alkyl]-5 nitroindazole derivatives. A self-protonation process involving the protonation of the nitro group was observed. The reactivity of the nitro-anion radical for these derivatives with glutathione, a biological relevant thiol, was also studied by cyclic voltammetry. These studies demonstrated that glutathione could react with radical species from 5-nitroindazole system. Also we demonstrated that nitro anion radicals show three different patterns of delocalization where the indazole 1-lateral chain does not have major influence. PMID- 17855163 TI - Prospective study of human metapneumovirus infection: diagnosis, typing and virus quantification in nasopharyngeal secretions from pediatric patients. AB - STUDY DESIGN: During the winter-spring seasons 2004-2005 and 2005-2006, 965 nasopharyngeal aspirates from 871 patients were examined for human metapneumovirus (hMPV) by both monoclonal antibodies (MAbs) and reverse transcription (RT)-PCR. RESULTS: Overall, 46 samples (4.8%) from 37 patients were positive for hMPV. Of these, 39 were positive by RT-PCR, and 35 by MAbs. Thus, using RT-PCR as a reference assay, the sensitivity, specificity, positive and negative predictive values of MAbs were 71.8%, 99.2%, 80.0% and 98.8%, respectively. Typing showed that concordant results were obtained in 32/46 (69.6%) strains (five untyped), whereas three strains were typed by MAbs only, and 11 by RT-PCR only. Finally, quantification of hMPV RNA allowed to correlate high viral load in nasopharyngeal secretions with acute respiratory symptoms in a group of 11 infants with acute lower respiratory tract infection examined upon admission and discharge from hospital, and a group of nine infants examined upon admission only. Conversely, hMPV etiology was questioned in a group of 14 infants with low viral load. CONCLUSIONS: MAbs may represent an alternative to or a complement to RT-PCR for detection and typing of hMPV strains, while hMPV RNA quantification may help in associating viral load with clinical symptoms. PMID- 17855164 TI - Biomimetic apatite coatings--carbonate substitution and preferred growth orientation. AB - Biomimetic apatite coatings were obtained by soaking chemically treated titanium in SBF with different HCO(3)(-) concentration. XRD, FTIR and Raman analyses were used to characterize phase composition and degree of carbonate substitution. The microstructure, elemental composition and preferred alignment of biomimetically precipitated crystallites were characterized by cross-sectional TEM analyses. According to XRD, the phase composition of precipitated coatings on chemically pre-treated titanium after exposure to SBF was identified as hydroxy carbonated apatite (HCA). A preferred c-axis orientation of the deposited crystals can be supposed due to the high relative peak intensities of the (002) diffraction line at 2theta=26 degrees compared to the 100% intensity peak of the (211) plane at 2theta=32 degrees . The crystallite size in direction of the c-axis of HCA decreased from 26 nm in SBF5 with a HCO(3)(-) concentration of 5 mmol/l to 19 nm in SBF27 with a HCO(3)(-) concentration of 27 mmol/l. Cross-sectional TEM analyses revealed that all distances correspond exactly to the hexagonal structure of hydroxyapatite. The HCO(3)(-) content in SBF also influences the composition of precipitated calcium phosphates. Biomimetic apatites were shown to have a general formula of Ca(10-x-y)Mg(y)(HPO(4))(x-z)(CO(3))(z)(PO(4))(6 x)(OH)(2-x-w)(CO(3))(w/2). According to FTIR and Raman analyses, it can be supposed that as long as the HCO(3)(-) concentration in the testing solutions is below 20 mmol/l, only B-type HCA (0 or = 35 years) cyclists performed an incremental exercise test to determine PO and HR at D-max, and peak physiological values. Participants then performed a TT30 during which mean HR and PO were measured for comparison with D-max values. The PO and HR at D-max were significantly correlated with the mean PO and HR during the TT30 (r=0.95, p<0.001 and r=0.88, p=0.002, respectively). Bland and Altman plots revealed a close agreement between D-max and average values sustained during the time trials for PO (95% CI=-14 to +3W) and HR (95% CI=-6 to +3bpm). This study has demonstrated that in veteran cyclists the D-max is accurate in predicting the highest average PO and HR that can be sustained during a 30-min time trial. PMID- 17855167 TI - The evolution of immunity: a low-life perspective. AB - Several of the key genes and pathways of vertebrate immunity appear to have much earlier origins than has been assumed previously and are present in some of the simplest of true animals. Surveys of recently released whole-genome sequences and large EST (expressed sequence tag) datasets imply that both the canonical Toll/Toll-like receptor (TLR) pathway and a prototypic complement-effector pathway, involving C3 and several membrane attack complex-perforin proteins, are present in corals and sea anemones, members of the basal phylum Cnidaria. However, both pathways are likely to have degenerated substantially in Hydra, leaving open the molecular mechanism by which antimicrobial activities are induced in this cnidarian. Surprisingly, the cnidarian genomes also encode a protein related to deuterostome RAG1 (recombination activation gene 1). The finding that RAG1 is likely to have originated from a Transib transposase implies that it might be possible to use in silico approaches to identify its target loci in 'lower' animals. PMID- 17855168 TI - The early benefits of a problem-based approach to teaching social inclusion using an online virtual town. AB - This article describes the delivery of a core pre-registration nursing and midwifery module centred on social inclusion. The module was previously delivered using a classroom-based problem-based learning approach. Difficulties with this approach led to changes to the module and its delivery. Logistic issues encouraged the module team to implement a blended learning approach using a virtual town to facilitate online learning and discussion activities. The paper describes and discusses the use of online learning technology to support student nurses and midwives. It highlights the benefits of this approach and outlines some of the experiences of the students including their evaluation of the virtual town. There is also an examination of some of the practical and theoretical issues related to both problem-based learning, online working and using a virtual town to support learning. This article outlines the approach taken and its implications. PMID- 17855169 TI - Response to Rolfe G (2007), nursing scholarship and the asymmetrical professor [Nurse Education in Practice, 7, 123-127] asymmetrical professors - unbalanced or misunderstood? PMID- 17855170 TI - Mannose binding lectin gene variants and susceptibility to tuberculosis in HIV-1 infected patients of South India. AB - Mannose binding lectin (MBL) plays an important role in innate immunity. Plasma MBL levels and MBL2 gene polymorphisms were studied in HIV-1 infected patients without tuberculosis (HIV+TB-) (n=151) and with tuberculosis (HIV+TB+) (n=109), HIV negative tuberculosis patients (HIV-TB+) (n=148) and healthy controls (n=146) by ELISA and genotyping by polymerase chain reaction based methods. MBL levels were significantly increased among HIV-TB+ and HIV+TB+ patients than controls and HIV+TB- patients (P<0.05). A significantly increased frequency of OO genotype of structural polymorphism and YY genotype of -221Y/X was observed among HIV-TB+ patients than controls. In HIV+TB+ patients, a significantly increased frequency of YA/YA diplotype (associated with very high MBL levels) was observed compared to controls (P=0.03). In HIV+TB+ patients, a significantly decreased frequency of medium MBL expression diplotypes (XA/XA and YA/YO) were noticed compared to HIV+TB- and healthy controls. The results suggest that YA/YA diplotype associated with very high MBL levels may predispose HIV-infected patients to tuberculosis while O/O genotype associated with very low MBL levels may be associated with susceptibility to tuberculosis in HIV uninfected individuals. Medium MBL expression diplotypes might protect against development of TB in HIV-infected patients. PMID- 17855171 TI - Lymphoma presenting as an ejection systolic murmur. AB - We report the case of a 22-year-old gentleman with non-Hodgkin's lymphoma who presented with a 3-week history of non-specific symptoms and an ejection systolic murmur. Urgent transthoracic echocardiography demonstrated a large anterior mediastinal mass compressing the right ventricular outflow tract that was confirmed on subsequent computerised tomography. PMID- 17855172 TI - Purification and partial characterization of glutathione transferase from the teleost Monopterus albus. AB - Glutathione transferases (GSTs) catalyze the transfer of glutathione to a variety of xenobiotic and toxic endogenous compounds. GSTs are phase II biotransformation enzymes and are proposed as biomarkers of environmental pollution. In this study, a cytosolic glutathione transferase (maGST) was purified from liver of the freshwater fish Monopterus albus by affinity chromatography. The maGST appeared to be a homodimer composed of two subunits each with a molecular weight of 26 kDa. This maGST showed high activity towards the substrates 1-chloro-2,4 dinitrobenzene (CDNB) and 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl). Kinetic analysis with CDNB as substrate revealed a K(m) of 0.28 mM and V(max) of 15.68 micromol/min per mg of protein. It had maximum activity in the pH range 7.0 7.5, a broad optimum T(m) range of 30 degrees C-55 degrees C, and a high thermal stability with 77% of its initial activity at 45 degrees C. This high thermal stability of maGST could be related to the physiological adaptation of M. albus to high temperatures in tropical and subtropical environments. PMID- 17855173 TI - Role of cytochrome P450 metabolites of arachidonic acid in regulation of corporal smooth muscle tone in diabetic and older rats. AB - This study examined the role of cytochrome P450 (CYP) metabolites of arachidonic acid (AA) to rat corporal smooth muscle tone. 11, 12-Epoxyeicosatrienoic acid (EET) (10(-11)-10(-6 )M) produced dose-dependent relaxation of rat (control; 10 weeks old) corpus cavernosum with a pD(2) value of 8.8+/-0.2 and a maximal relaxation of 80+/-9%, whereas 20-hydroxyeicosatetraenoic (20-HETE) did not have an effect. EET-mediated relaxation of corpus cavernosum was attenuated by 71+/ 3%, 55+/-2%, 53+/-5% and 84+/-3% in the presence of nitro-L-arginine methyl ester (L-NAME) (10(-4) M), an inhibitor of nitric oxide (NO) synthase, iberiotoxin (5 x 10(-8) M), an inhibitor of calcium-activated potassium (BK) channels, glibenclamide (10(-5) M), an inhibitor of ATP-sensitive K(+) channels or 1H [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10(-5) M), an inhibitor of soluble guanylyl cyclase, respectively. EET-mediated relaxation of rat corpus cavernosum was significantly less in the streptozotocin (STZ)-treated (diabetic) and 30 weeks old (older) animals compared to control. Carbachol (10(-9)-10(-4) M) induced relaxation was significantly reduced whereas phenylephrine (PE) (10(-9)-5 x 10(-3) M)-induced contraction was significantly increased in the cavernosum strips from old and diabetic rats compared to the control. Pre-incubation of the cavernosum strips obtained from control, older or diabetic rats with N-hydroxy-N' (4-butyl-2-methyl-phenyl)-formamidine (HET0016), a selective inhibitor of 20-HETE synthesis, or 1-cyclohexyl-3-dodecyl urea (CDU), a specific inhibitor of soluble epoxide hydrolase (sEH) resulted in a significant attenuation of PE-induced contraction and improvement in carbachol-induced relaxation. We conclude that 11, 12-EET-induced relaxation of the rat corpus cavernosum involves activation of cGMP/NO pathway as well as activation of ATP-sensitive K(+) channels and BK channels. These results also suggest that inhibition of 20-HETE production or reduction of EET inactivation may have therapeutic potential to prevent erectile dysfunction associated with diabetes and aging. PMID- 17855174 TI - Hydrogen peroxide induces apoptosis in HeLa cells through mitochondrial pathway. AB - Cervical cancer is the most common cancer amongst females in India and is associated with high risk HPVs, reactive oxygen species (ROS), and excessive inflammation in most cases. ROS in turn affects the expression of pro- and anti apoptotic proteins. The objective of the present study was to elucidate the effect of hydrogen peroxide (H(2)O(2)) on apoptotic signaling molecules in vitro. HeLa cell line expresses the Human papilloma virus - 18, E6 oncoprotein which causes the ubiquitin mediated degradation of p53 protein and is thus p53 deficient. p53 is known to act as a cellular stress sensor and triggers apoptosis. p73, a member of the p53 family also induces apoptosis in response to DNA damaging agents but unlike p53, it is infrequently mutated in human tumors. We demonstrate here, that in HeLa cells, apoptosis is triggered by H(2)O(2) via the mitochondrial pathway involving upregulation of p73, and its downstream target Bax. This was accompanied by upregulation of ERK, JNK, c-Myc, Hsp-70 and down regulation of anti-apoptotic Bcl-XL, release of cytochrome c from mitochondria and activation of caspases-9 and -3. PMID- 17855175 TI - Analysis of the structural consensus of the zinc coordination centers of metalloprotein structures. AB - In a recent sequence-analysis study it was concluded that up to 10% of the human proteome could be comprised of zinc proteins, quite varied in the functional spread. The native structures of only few of the proteins are actually established. The elucidation of rest of the sequences of not just human but even other actively investigated genomes may benefit from knowledge of the structural consensus of the zinc-binding centers of the currently known zinc proteins. Nearly four hundred X-ray and NMR structures in the database of zinc-protein structures available as of April 2007 were investigated for geometry and conformation in the zinc-binding centers; separately for the structural and catalytic proteins and individually in the zinc centers coordinated to three and four amino-acid ligands. Enhanced cysteine involvement in agreement with the observation in human proteome has been detected in contrast with previous reports. Deviations from ideal coordination geometries are detected, possible underlying reasons are investigated, and correlations of geometry and conformation in zinc-coordination centers with protein function are established, providing possible benchmarks for putative zinc-binding patterns of the burgeoning genome data. PMID- 17855176 TI - Hydrogel nanocomposites as remote-controlled biomaterials. AB - Nanocomposite hydrogels are a new class of intelligent materials which have recently attracted interest as biomaterials. In this study, magnetic nanocomposites of temperature-sensitive hydrogels have been developed and demonstrated to be responsive to alternating magnetic fields. Nanocomposites were synthesized by incorporation of superparamagnetic Fe(3)O(4) particles in negative temperature-sensitive poly(N-isopropylacrylamide) hydrogels. The systems were characterized for temperature-responsive swelling, remote heating on application of an alternating magnetic field and remote-controlled drug delivery applications. The rise in temperature in external alternating magnetic field depends on the Fe(3)O(4) particle loading of the system. Preliminary studies on remote-controlled drug release showed reduced release in the presence of an alternating magnetic field. PMID- 17855177 TI - Long term results of radial tunnel release--the effect of co-existing tennis elbow, multiple compression syndromes and workers' compensation. AB - SUMMARY: Surgical decompression of radial tunnel syndrome (RTS) remains controversial because the results are unpredictable. This study is a retrospective analysis of the long term outcomes of RTS release and a comparison of our findings with previous studies. Thirty-three extremities in 31 patients underwent decompression for radial tunnel syndrome between 1994 and 2003, of which 27 extremities in 25 patients were available for long term follow up after an average of 57 months (range 16 to 106 months). Outcomes were evaluated using the criteria of Ritts et al. (1987). For 16 patients (18 of 27 extremities), the outcome was rated as good (67%), for four patients (four extremities) as fair (15%), and for five patients (five extremities) as poor (18%). The outcome was better in patients with simple RTS (86% good results) compared with patients with additional nerve compression syndromes (57% good results), or patients with coexisting lateral epicondylitis (70% vs 43% good results), or patients who were receiving workers' compensation (73% vs 58% good results). One-third of patients still had moderate or severe disability which affected their ability to work, but 82% had relief of their pain. Surgical decompression is therefore beneficial for simple RTS, but may be less successful if there are co-existing additional nerve compression syndromes or lateral epicondylitis or if the patient is receiving workers'compensation. PMID- 17855178 TI - Osteocytes subjected to fluid flow inhibit osteoclast formation and bone resorption. AB - Bone has the capacity to alter its mass and structure to its mechanical environment. Osteocytes are the predominant bone cells and it is generally accepted that the osteocytes are the professional mechanosensors of bone. A strain-derived fluid flow through the lacuno-canalicular porosity seems to mechanically activate them, resulting in the production of signalling molecules such as nitric oxide (NO). We hypothesize that mechanically stimulated osteocytes modulate osteoclast formation and activity via soluble factors, thus affecting bone resorption. Osteocytes, osteoblasts, and periosteal fibroblasts were isolated from fetal chicken calvariae via enzymatic digestion. The periosteal fibroblasts were obtained from the periostea. Osteocytes were separated from osteoblasts by immunomagnetic separation. Cells were mechanically stimulated for 1 h with pulsating fluid flow (PFF, 0.70 +/- 0.30 Pa) at 5 Hz, or kept under static conditions. Conditioned medium was collected after 60 min. The effect of conditioned medium on osteoclastogenesis was tested on mouse bone marrow cells in the presence of macrophage colony stimulating factor and receptor activator of NF kappaB ligand. After 6 days of culture, osteoclast formation and bone resorption was determined. Osteocytes subjected to 1 h pulsating fluid flow produced conditioned medium that inhibited the formation of osteoclasts. For osteoblast PFF-conditioned medium, such effect was, to a lesser extent, also observed, but not for periosteal fibroblast PFF-conditioned medium. Furthermore, PFF-treated osteocytes, but not osteoblast or periosteal fibroblast, produced conditioned medium that resulted in a decreased bone resorption. The NO synthase inhibitor N(G)-nitro-L-arginine methyl ester attenuated the inhibitory effects of osteocyte PFF-conditioned medium on osteoclast formation and resorption. We conclude that osteocytes subjected to PFF inhibit osteoclast formation and resorption via soluble factors, and the release of these factors was at least partially dependent on activation of an NO pathway in osteocytes in response to PFF. Thus, the osteocyte appears to be more responsive to PFF than the osteoblast or periosteal fibroblast regarding to the production of soluble factors affecting osteoclast formation and bone resorption. PMID- 17855179 TI - The effectiveness of intravenous 5-fluorouracil-containing chemotherapy after curative resection for gastric carcinoma: A systematic review of published randomized controlled trials. AB - This is a review of randomized controlled trials of intravenous 5-flurorouracil (5-FU)-containing chemotherapy after curative resection versus surgery alone in patients with gastric carcinoma to determine the impact on survival rate, safety and economics. Data sources were the Cochrane Library (2006, Issue 2), Pub Medline and Chinese Biomedical Database. We included 22 randomized controlled trials comparing 4501 patients. Intravenous 5-FU-containing chemotherapy after curative resection had a slightly significant improvement in 3-, 5- and 7-year overall survival rate (OR 1.49, 1.41 and 1.32). No benefit of postoperative disease-free survival rate was induced by 5-FU-containing chemotherapy. Sensitivity analysis was restricted to trials with the highest methodological quality, and the result was similar when the studies with Jadad score less than 3' were excluded. Subgroup analyses found borderline improved overall survival rate in both Western and Eastern countries but the statistical significance was stronger in the Eastern subset. The combinations of 5-FU plus mitomycin C, 5-FU plus cytosine arabinoside and 5-FU plus adriamycin or epidoxorubicin induced potentially more improvement of 3- and 5-year overall survival rates. Severe toxicities were reported in 1629 patients from 15 included trials, and hematological and gastrointestinal toxicities were the most remarkable side effects, around 5%-15% respectively. The chemotherapy-related overall mortality was 1.1%. No trials mentioned cost-effectiveness analysis. Although the results provide some evidence of a beneficial effect of adjuvant chemotherapy with 5-FU containing regimens, they are inconclusive due to the limitations of methodological quality of including randomized controlled trials. Large scale randomized controlled trials with a positive result are still mandatory before postoperative chemotherapy are recommended. PMID- 17855180 TI - Carbapenem resistance in clinical isolates of Pseudomonas aeruginosa. AB - The objectives of this study were to identify the carbapenem resistance mechanisms of clinical Pseudomonas aeruginosa isolates. The strains resistant to imipenem had lost only the OprD protein, the isolates resistant to imipenem and meropenem had both loss of the OprD porin and reduced minimum inhibitory concentrations (MICs) in the presence of efflux pump inhibitors. In the isolates in which efflux had been identified (n=2) only 1 isolate had a mutation in the mexR gene corresponding to a glutamine to a stop codon change at amino acid 106. This has not been previously identified. There were no significant changes in the mexT genes. No mutations previously associated with the upregulation of the carbapenem efflux pumps in in vitro generated resistant isolates were identified in any of the clinical isolates. Therefore, the resistance mechanisms identified by development of carbapenem resistance in vitro are not sufficient to understand carbapenem resistance development in clinical isolates. PMID- 17855181 TI - Patterns of resistance to beta-lactams and characterization of beta-lactamases in Escherichia coli isolates from children in Tunisia. AB - Seventy-six (75.2%) of 101 Escherichia coli isolates, collected over a 2-month period in 2002 at the Children's Hospital of Tunis (Tunisia), were resistant to at least one beta-lactam. They produced beta-lactamases which were further characterized by spectrophotometry, isoelectric focusing (IEF) and PCR. Seventy five isolates had a pI 5.4 beta-lactamase and one isolate expressed a pI 5.6 beta lactamase. These beta-lactamases were active against penicillins and cephalothin. Nineteen of 76 isolates were resistant to ticarcillin-clavulanic acid combination. The bla(TEM) gene was detected in 71 isolates, all expressed a pI 5.4 beta-lactamase that was assumed to be TEM-1 or inhibitor-resistant TEM (IRT). Thirty-eight of 76 isolates showed one weak band on IEF with pIs ranging from 8.2 to >9, suggesting low level expression of the chromosomal AmpC beta-lactamase. Five of 76 isolates produced extended-spectrum beta-lactamases (ESBLs), with a basic pI of 7.9 or 8.7, active on penicillins, extended-spectrum cephalosporins, but not on cefoxitin. bla(SHV) genes were detected in three isolates producing pI 7.9 ESBLs but not in two isolates expressing pI 8.7 ESBLs. These latter showed strong cefotaxime-hydrolyzing activities. Hence, they might be CTX-M-type ESBLs. PMID- 17855182 TI - Evaluation of different compounds as quorum sensing inhibitors in Pseudomonas aeruginosa. AB - Quorum sensing (QS) controls systems affecting the pathogenicity of many microorganisms; its interruption has an anti-pathogenic effect and can be used in the treatment of bacterial infections. In this study we evaluated QS regulation by Pseudomonas aeruginosa strains and QS inhibition (QSI) by different compounds. The inhibitory activity of 3 macrolide and 3 lincosamide drugs, resveratrol, garlic extract and N-acetylcysteine was tested on 4 P. aeruginosa strains isolated from cystic fibrosis (CF) patients using Chromobacterium violaceum ATCC 12472 as biomonitor. One P. aeruginosa strain, lincomycin and N-acetylcysteine did not show QSI, contrary to other compounds and P. aeruginosa strains. These results indicate that QSI evaluation should be taken into account in the design of new therapeutic strategies to treat P. aeruginosa infections, especially in patients infected by antibiotic-resistant bacteria. PMID- 17855183 TI - Antipneumococcal activity of ertapenem compared with gatifloxacin in a temperature-sensitive murine model of acute pneumonia. AB - Fluoroquinolone-resistance among pneumococci is low; however the number of isolates with a single ParC mutation has increased. Consequently, more potent agents are needed to minimize resistance selection. We investigated the efficacy of ertapenem versus gatifloxacin in a temperature-sensitive mouse model of pneumonia caused by a wildtype Streptococcus pneumoniae strain (A66) and an isogenic mutant with a ParC mutation (R222). Treatment started at 24 h and lasted for 5 days. Temperature was used to assess disease progression before and during treatment. Of mice infected with either strain and treated at an early stage of infection, 79-94% of those given ertapenem survived compared with 56-61% given gatifloxacin. If treated at a later stage, the results were similar for ertapenem (71-84%) but were considerably lower for gatifloxacin (17-33%). Ertapenem was as bactericidal as gatifloxacin against A66 (94-100% vs 92-100%) but was superior to gatifloxacin against R222 (95-100% vs 50-77%). Ertapenem is a promising new treatment for patients with pneumococcal pneumonia, including those at risk of infection with a fluoroquinolone-resistant strain. PMID- 17855184 TI - Economic evaluation of linezolid versus teicoplanin for the treatment of infections caused by gram-positive microorganisms in Spain. AB - The aim of this study was to perform a comparative cost-effectiveness analysis of linezolid vs teicoplanin (i.v., switching to oral/i.m. respectively) in Spain. A decision tree model was used with the results of a randomized, comparative, controlled clinical trial with linezolid vs teicoplanin in the treatment of infections caused by Gram-positive microorganisms, with a timeline of 31 days. The efficacy endpoint was the percentage of patients with clinical healing or improvement in their infection. Direct medical costs were included using Spanish 2005 prices. Average cost per patient, average cost-effectiveness ratio and several sensitivity analyses were carried out. In the intent-to-treat (ITT) analysis linezolid obtained a higher percentage of therapeutic success than teicoplanin (95.5% vs 87.6% respectively, p = 0.005), both with similar tolerability. The average cost per treated patient was euro 8,064.76 for linezolid vs euro 8,727.36 for teicoplanin, with an incremental cost of euro 622.59 (-7,6%). Linezolid yielded a lower average cost-effectiveness ratio, euro 8,444.78 (8,195.90 - 8,709.25) than teicoplanin, euro 9,962.74 (9,465.68 - 10,502.23), with a slight reduction in average cost per successfully treated patient of 15.2% ( euro 1,517.96). The results were robust to the sensitivity analysis. In conclusion, linezolid is a more cost-effective option than teicoplanin in the treatment of infections caused by Gram-positive microorganisms, since it offers superior clinical benefits with a lower use of associated resources. PMID- 17855185 TI - Metronidazole single versus multiple daily dosing in serious intraabdominal/pelvic and diabetic foot infections. AB - The purpose of the study was to compare the clinical efficacy of once-daily versus multiple dose regimens of metronidazole in inpatients with serious/systemic Bacteroides fragilis infections, i.e., intraabdominal/pelvic and diabetic foot infections. A retrospective chart review was performed on 145 adult inpatients who received combination therapy with metronidazole for B. fragilis abdominal/pelvic infection or diabetic (deep) foot infections/osteomyelitis. Exclusion criteria included metronidazole given for indications other than those mentioned, patients who received only one dose of metronidazole, and patients who received oral metronidazole only. The 145 patients were in two groups: 66 patients in the metronidazole 1 g (i.v.) q24h (Group A) and 79 patients who received metronidazole 500 mg (i.v./p.o.) q6-8h dosing (Group B). Patient demographics included age, gender, indications of metronidazole, concomitant, antibiotics, and co-morbidities. Data collection also included length of stay (LOS), antibiotic days, and clinical outcomes. The 145 patients in our study had a mean age of 66 years, 61% were female and 39% male. Most patients were being treated for definitive intraabdominal/pelvic infections (82%), or probable intraabdominal/pelvic infections (22%). Only 6% had deep diabetic foot infections of osteomyelitis (percentages exceed 100% since a patient can have more than one indication) and were included since B. fragilis is also and important pathogen in diabetic osteomyelitis. Group A patients had more concomitant antibiotics and co morbidities (p < 0.0001 and p < 0.05 respectively, chi-square test for trend) than Group B patients. There were no statistically significant differences between groups A and B for LOS and antibiotic days (p = 0.42 and p = 0.92 respectively, by rank-sum test), but after adjusting for concomitant antibiotics and co-morbidities Group A patients had clinically shorter LOS and fewer antibiotic days. Unadjusted mortality and failure rates were non-significantly higher in group A (relative ratios of 12.1%/6.3% = 6.3% = 1.91 and 18.2%/ 10.1% = 1.80 respectively), but after adjusting for concomitant antibiotics and co morbidities with stratification analysis, groups A and B were virtually the same (risk differences of 70 years of age (P=0.048).We conclude that the biweekly administration of a docetaxel/gemcitabine combination with G-CSF support constitutes a tolerable and convenient regimen for the treatment of elderly patients with advanced NSCLC, with efficacy similar to that reported in other regimens. Hence, this two-drug combination appears promising and warrants further evaluation. PMID- 17855190 TI - Multicenter phase II trial of combination chemotherapy with weekly paclitaxel and 5-fluorouracil for the treatment of advanced or recurrent gastric carcinoma. AB - The aim of this study was to investigate the efficacy and safety of combination chemotherapy with weekly paclitaxel and 5-fluorouracil (5-FU) as first-line treatment in patients with advanced or recurrent gastric carcinoma. A total of 65 patients were treated with the following regimen, administered every 28 days; 5 FU 600 mg/m2 by 24-hour continuous infusion from days 1 through 5, and weekly paclitaxel 80 mg/m2 by 3-hour intravenous infusion on days 8, 14, and 21. A total of 272 cycles were conducted with a median of 4 (2-13) cycles per case. Out of 57 patients with measurable disease by RECIST criteria, there were 2 complete responses (3.5%), 20 partial responses (35.1%) and 25 cases with stable disease (43.9%). The overall response rate was 38.6% (95%CI: 26.0-51.2%). The median survival time and 1-year survival rates were 329 days and 47.4%, respectively. Both hematologic and non-hematologic toxicities were well tolerated. PMID- 17855191 TI - Mucinous cancer of the appendix: challenges in diagnosis and treatment. AB - The authors report and discuss a case of a mucinous carcinoma of the appendix, a rare entity with a distinct natural history that poses diagnostic and therapeutic challenges. Mucinous peritoneal carcinomatosis is most commonly associated with primary tumors of the appendix and colon. Typically, spread remains confined to the abdominal cavity. Imaging assessment of these mucinous lesions is difficult, while tumor markers (CEA and CA19.9) may be surrogates for extent of disease. Treatment consists of surgical debulking, sometimes coupled with intraperitoneal drug delivery, but recurrence is universal. New treatment approaches are needed. Mucin genes are regulated in part by epidermal growth factor receptor signaling. Therefore, we initiated a phase II study of cetuximab for mucinous peritoneal carcinomatosis, that was part of this patient's treatment. PMID- 17855192 TI - Acute methotrexate-induced encephalopathy--causal relation to homozygous allelic state for MTR c.2756A>G (D919G)? AB - Methotrexate (MTX) is widely used in the treatment of hematological diseases. The typical side-effects of high-dose MTX chemotherapy on the CNS range from asymptomatic white matter changes to severe CNS demyelination. MTX neuro - toxicity has been described to be associated with homocysteine and folate levels as well as genetic variants affecting methionine metabolism. Here we describe a case of severe, acute MTX-induced encephalopathy in a patient who was found to be homozygous for the rare missense variant methionine synthase (MTR) c.2756A>G (D919G), which may have modified the effect of MTX on homocysteine metabolism. This finding encourages further studies to determine to what extent the individual conditions of folate and methionine metabolism influence the effects or side-effects of MTX treatment. PMID- 17855193 TI - A combination of mathematical and statistical models to distinguish between "susceptible" and "resistant" clusters in the susceptibility disk diffusion method. PMID- 17855194 TI - First report of molecular characterization of carbapenem-resistant Acinetobacter baumannii in different intensive care units in University Hospital Split, Croatia. PMID- 17855195 TI - Ureaplasma urealyticum and Mycoplasma hominis susceptibility to antimicrobial agents. PMID- 17855196 TI - First detection of VIM-1 type metallo-beta-lactamase in a multidrug-resistant Klebsiella pneumoniae clinical isolate from Turkey also producing the CTX-M-15 extended-spectrum beta-lactamase. PMID- 17855197 TI - Excellent results of contemporary coronary artery bypass grafting with systematic application of modern perioperative strategies. AB - BACKGROUND: The patient population referred for coronary artery bypass grafting (CABG) has become more challenging. The surgical population is aging and patients present with significant preoperative comorbidities. This worsening risk profile has led to the development of operative techniques (off-pump CABG) and perioperative measures (epi-aortic scanning, intensive insulin therapy) to preserve the quality of care following CABG. The aim of this study was to determine the outcome of contemporary CABG following the implementation of the above measures in our practice. METHODS: We retrospectively analyzed prospectively collected data of 2725 patients undergoing CABG between 01/1998 and 12/2005 (mean age, 65 +/- 11 years; 843 [31%] female; mean ejection fraction, 45% +/- 14%). Outcome measures included hospital mortality, postoperative complications, and long-term survival and independent predictors of outcome. Subgroup analyses were performed for 2 study periods (1998-2002 versus 2003-2005) where the above measures were implemented and for patients undergoing conventional versus off-pump CABG. RESULTS: When comparing the 2 study periods, we observed a substantial worsening of the risk profile with an increased EuroSCORE predicted mortality from 6.4% +/- 6.8% to 7.0% +/- 7.8% (P = .028). During the same period, operative mortality decreased from 2.4% to 0.7% (P < .001). This reduction in mortality was also observed in diabetic patients (3.1% versus 1.0%, P = .021) and those with low ejection fraction (4% versus 2.6%, P = not significant). Off-pump procedures were performed with an increasing frequency in high-risk patients in whom we obtained excellent results. Finally, we observed a reduction of postoperative complications including respiratory failure (P = .013), gastrointestinal complications (P = .017), and stroke (P = .094). Independent predictors of mortality included renal failure (OR = 5.7), peripheral vascular disease (OR = 2.9), intra-aortic balloon pump (OR = 4.8), reoperation (OR = 3.3), and hypertension (OR = 2.3). CONCLUSION: Despite a worsening case mix, contemporary CABG can be performed with excellent results (operative mortality < 1%). Off-pump CABG performed in very high-risk patients obtains results similar to those of the general CABG population. Diabetes and ejection fraction were not independent predictors of early outcome. In our experience, these excellent outcomes were achieved by adopting an operative approach using modern perioperative management (epi-aortic scanning, intensive insulin therapy) and surgical techniques (off-pump CABG) based on individual patients. PMID- 17855198 TI - A novel approach for pain management in cardiac surgery via median sternotomy: bilateral single-shot paravertebral blocks. AB - Regional analgesia has entered cardiac anesthesia in the form of spinal or epidural analgesia. However, the risk of spinal or epidural hematoma is a constant worry. Alternative regional techniques might be applicable in cardiac surgery. The purpose of this study is to present a novel technique of bilateral single-shot paravertebral blocks (BSS-PVB) for cardiac surgery via median sternotomy and compare its efficacy versus high thoracic epidural analgesia (TEA). Fifty-two patients were compared in this prospective cohort audit. In 26 patients, cardiac surgery was performed using low-dose fentanyl/BSS-PVB (bilateral blocks of 3 mL bupivacaine 0.5% each, T1-7) and general anesthesia; in another 26 patients, TEA (bupivacaine 0.125% at 10 mL/hour) and general anesthesia were used. Patients were assigned to cohorts according to their preoperative data and types of surgery. All patient data are shown as mean +/- SD; pain scores were compared between groups using the t test immediately, 6 hours, and 24 hours after surgery (P < .05). In the BSS-PVB-group (19 men, 7 women), mean age was 65 +/- 11 years, weight 74 +/- 16 kg, ejection fraction 59% +/- 12%, and duration of surgery 130 +/- 27 minutes; in the TEA-group (17 men, 9 women), mean age was 63 +/- 10 years, weight 75 +/- 16 kg, ejection fraction 58% +/- 12%, and duration of surgery 113 +/- 27 minutes. These data and preoperative comorbidity variables were not significantly different between the two groups. In each group, 18 patients underwent off-pump coronary artery bypass grafting, 3 on pump and 5 mitral valve replacements. All patients were successfully immediately extubated. Postoperative pain scores were at any point significantly lower with TEA, immediately at 2.4 +/- 2.2 versus 3.7 +/- 2.6, at 6 hours at 1.1 +/- 1.5 versus 2.4 +/- 1.8, and at 24 hours at 1.0 +/- 1.4 versus 2.3 +/- 1.6 (0 = no pain, 10 = maximum pain). There was no complications related to epidural catheter placement or BSS-PVB. Using both techniques, immediate extubation after cardiac surgery is feasible; TEA provides better pain relief after cardiac surgery than BSS-PVB. PMID- 17855199 TI - Endoscopic radial artery harvesting reduces postoperative pain and neurologic complications. AB - BACKGROUND: Endoscopic radial artery harvest provides better cosmetic result without compromising the quality of the graft. We sought to compare postoperative harvesting site neurologic and vascular outcome. METHODS: From 10/2002 until 10/2004, 50 patients were randomized to have their radial artery harvested for coronary bypass either endoscopically (group A, n = 25) or conventionally (group B, n = 25). Radial arteries were preoperatively evaluated by Doppler echocardiography. Neurologic and functional status was assessed by a self reporting questionnaire with a semiquantitative (1-5) scale. Vascular status of the forearm was assessed by control echocardiography. RESULTS: At an average follow-up of 37 +/- 7 months, patients undergoing endoscopic radial artery harvesting had less overall neurologic complications (11 versus 17 patients, P = .023) and they were less severe (0.8 +/- 1.1 versus 2.2 +/- 1.2; P < .001). Ulnar flow increase was similar among the groups: 13.1 +/- 5.43 cm/s in group A versus 15.9 +/- 4.9 cm/s in group B (P = .147) as well as ulnar artery diameter increase 0.29 +/- 0.16 mm in group A versus 0.29 +/- 0.26 cm in group B (P = .914). CONCLUSION: Endoscopic radial artery is safe and does not compromise graft quality or forearm and hand circulation postoperatively. Along with providing a better cosmetic result, endoscopic artery harvesting reduces postoperative harvesting site pain and neurologic complications. PMID- 17855200 TI - Sternal wound infections following cardiac surgery: risk factor analysis and interdisciplinary treatment. AB - OBJECTIVE: Sternal wound infections are a serious complication after cardiac surgery. Although a variety of treatment algorithms has been published, the ideal operative treatment of complicated median sternotomy wounds is the subject of ongoing controversy. METHODS: In a retrospective review, 3016 consecutive open heart surgery patients between January 2003 and June 2006 were evaluated: 65.6% underwent coronary artery bypass surgery (CABG), 16.3% cardiac valve replacement, 13.5% combined CABG and valve replacement, 2.8% aortic reconstruction or replacement, 0.6% artificial heart implantation, and 1.2% cardiac transplantation. RESULTS: Sixty-three patients (2.1%) developed sternal wound infections. Fifty-six wounds were treated with debridement, irrigation, and re wiring. Thirty-four patients were treated using vacuum-assisted closure therapy. Nineteen of these patients eventually required plastic surgical coverage with either rectus abdominis or pectoralis major flaps. Diabetes mellitus, rethoracotomy, duration of operation and, interestingly, the time of operation (morning versus afternoon) presented significant risk factors for development of sternal wound infections (P <.05). Three patients developed partial flap necrosis and required a second flap. Eventually, all defects were successfully reconstructed and there was no recurrent ostemyelitis noticed over the entire observation period (follow-up, 23 +/- 13 months). DISCUSSION: Patients at risk for development of sternal wound infections may be preferably operated in the morning at first position. Vaccuum-assisted closure therapy acts as a link between radical debridement and definitive plastic coverage. The type of flap is individually chosen based on location of the defect and availability of certain vascular axis. The presented interdisciplinary approach with radical surgical debridement, application of subatmospheric pressure dressings, and early involvement of the plastic surgical team allows efficient treatment of infected median sternotomy wounds. PMID- 17855201 TI - Kinking of internal thoracic artery graft without symptoms: should it be revised? AB - BACKGROUND: Surgery or intervention therapy has been performed to correct kinks of internal thoracic artery (ITA) grafts. The aim of this study was to evaluate the natural course of the ITA graft kink and to clarify whether surgery or intervention therapy should be performed in asymptomatic patients during the early postoperative period. METHODS: We investigated the early and follow-up angiographic results of ITA graft kinks in 7 consecutive patients who did not undergo surgical or interventional correction. The graft diameter and percentage of diameter stenosis at the kink site were compared between the early postoperative angiography and the follow-up angiography. RESULTS: Early postoperative angiography revealed that the diameter stenosis at the kink site was 60.1% +/- 6.9% (range, 51 to 69) and the diameter at the kink site was 0.92 +/- 0.20 mm (range, 0.63% to 1.25%). The ITA kinks disappeared in all the patients and the diameter of the ITA graft adjacent to the kink was not significantly changed on the follow-up angiography. No luminal irregularity or indentation was shown. All the patients had been free from cardiac events until the follow-up angiography. CONCLUSION: Kinking of an ITA graft that's seen on the early postoperative angiography might improve without surgery or intervention. The natural course of ITA graft kinks should be considered when detecting these kinks on the early postoperative angiography when the patient is asymptomatic. PMID- 17855202 TI - The effect of surgical treatment for secundum atrial septal defect in patients more than 30 years old. AB - BACKGROUND: We prospectively examined whether surgical treatment of secundum atrial septal defects in patients 30 years old improves their early- and mid-term clinical outcomes. Our clinical experience is reviewed to assess the importance of surgical management in elderly patients with atrial septal defect. METHODS: We analyzed 41 patients older than 30 years of age who underwent surgical correction of a secundum atrial septal defect. To evaluate the effects of surgical treatment, we compared functional capacity, diuretic administration, rhythm status, and echocardiographic parameters of all patients before and after the operation. RESULTS: The median follow-up period was 4.2 years (range, 6 months-7 years). There were no operative deaths. Functional class in most of the patients improved after operation. Two patients reverted to normal sinus rhythm after the operation. There was only one new atrial fibrilation among patients in the postoperative term. Right atrial and right ventricular dimensions and pulmonary artery pressures were significantly decreased, and ejection fractions were significantly increased after the operation. The need for diuretic treatment was decreased after surgical repair. No residual intracardiac shunts were identified during follow-up. There were no cerebrovascular thromboembolic accidents in the early postoperative period. CONCLUSION: Surgical closure of atrial septal defects in patients over 30 years old can improve their clinical status and prevent right ventricular dilatation and insufficiency. The operation must be performed as soon as possible, even if the symptoms or the hemodynamic impact seem to be minimal. PMID- 17855203 TI - Image-guided quantification of cardioplegia delivery during cardiac surgery. AB - BACKGROUND: Homogenous distribution of cardioplegia delivered to the myocardium has been identified as an important predictor of post-cardiopulmonary bypass ventricular recovery and function. Presently, a method to determine adequate distribution of cardioplegia in patients during cardiac surgery does not exist. The goal of this study was to evaluate the feasibility of quantifying cardioplegia delivery using a novel, noninvasive optical method. Such a system would permit instantaneous imaging of jeopardized myocardium and allow immediate, intraoperative corrective measures. METHODS: We have previously developed a portable, intraoperative near-infrared (NIR) fluorescence imaging system for use in large animal cardiac surgery that simultaneously displays color video and NIR fluorescent images of the surgical field. By introducing exogenous, NIR fluorophores, specific cardiac functions can be visualized in real-time. RESULTS: In a porcine cardiopulmonary bypass model, we demonstrate that the FDA-approved intravascular fluorophore indocyanine green (ICG) permits real-time assessment of cardioplegia delivery. ICG was injected into an aortic root and/or transatrial coronary sinus catheter during delivery of crystalloid cardioplegia solution. Segmental distribution was immediately noted at the time of injection. In a subset of animals, simulated coronary occlusions resulted in imaging defects consistent with poor cardioplegia delivery and jeopardized myocardium. Videodensitometric analysis was performed on-line to quantify distribution to the right ventricle and left ventricle. CONCLUSION: We report the development of a novel, noninvasive, intraoperative technique that can easily and safely provide a visual assessment of cardioplegia delivery (antegrade and/or retrograde) and that offers the potential to quantify the relative segmental distribution during cardiac surgical procedures. PMID- 17855204 TI - Detection of coronary arteries and evaluation of anastomoses with a commercially available 15-MHz, broadband, linear array transducer. AB - BACKGROUND: In coronary artery bypass surgery the detection of the target vessels can be difficult due to their intramural location, coverage by adipose tissue, calcification, or fibrous tissue formation. Their identification is especially critical during off-pump coronary artery bypass (OPCAB) and minimally invasive direct coronary artery bypass (MIDCAB) surgeries. Our objectives were to identify whether (1) the epimyocardial use of the broadband linear array transducer CL15-7 allows a clear and rapid identification of the target artery during on-pump coronary bypass (CPB), OPCAB and MIDCAB surgeries; and (2) if this transducer is helpful in investigating the anastomotic morphology with 2D and color flow Doppler. METHODS: Thirty-two patients without a visually identifiable left anterior descending artery (LAD) were included in the study and epimyocardial ultrasonography was performed. Stabilization of the beating heart was used in 19 patients; in 13 patients, the surgery was carried out with CPB on the arrested heart. Two-dimensional ultrasound alone, or in combination with color Doppler, was used to identify the affected vessel as well as a suitable anastomosis site. Pulsed wave Doppler had to be used occasionally to differentiate between artery and vein. Patency of the anastomoses was established with color Doppler immediately after reinitiating blood flow. An evaluation of the distal graft diameter, its length, and the quality of the anastomosis was made with 2D and color Doppler. Transit-time Doppler flow was used to confirm patency. RESULTS: The LAD could be identified ultrasonographically in all 32 patients at a depth of 3 to 15 mm. The right coronary artery (RCA) was located at a depth of 3 to 10 mm in the 5 patients where this vessel was to be bypassed. The coronary arteries located on the lateral or posterior aspect of the heart could not be reached due to the shape and rigidity of the transducer handle. The intended anastomosis sites of the LAD and RCA were identified with ultrasound according to their topography and morphology. In all cases the vessel could be dissected and bypassed without undue damage or bleeding. In one OPCAB patient, the LAD was identified in close proximity to the overlying vein along the whole of the anterior wall. This resulted in conversion to CPB, thus facilitating secure exposure of the LAD. The ultrasonographic visibility of the left internal mammary artery to LAD and saphenous vein graft to RCA anastomoses was excellent, and patency correlated well with the transit time flow measurements. CONCLUSION: The CL15-7 transducer gives excellent near field visibility of the LAD and RCA. This is extremely valuable for the safe dissection of these vessels, especially during off-pump coronary surgery. The anatomical morphology of the anastomoses can be identified but, due to the shape of the transducer handle, only the coronary arteries on the anterior surface of the heart can be evaluated. A flexible, rather than a rigid, hockey stick-shaped handle would eliminate this problem. Training is essential to obtain reliable results. PMID- 17855205 TI - Preoperative fibrinogen levels as a predictor of postoperative bleeding after open heart surgery. AB - BACKGROUND: Open heart surgery still involving major bleeding continues to be a major challenge after cardiac surgery and is also a significant cause of morbidity and mortality. Most hemostatic factors are intercorrelated with postoperative bleeding, and fibrinogen seems the most fundamental hemostatic risk factor for open heart surgery. METHODS: The study included 97 patients who underwent elective coronary artery surgery (78 men and 19 women; mean age, 60.9 +/- 10.3). Preoperative blood samples were obtained and preoprative quantitative determination of plasma fibrinogen levels were measured by the clotting method of Clauss using the fibrinogen kit. Patients were operated on by the same team and the same technique. The total amount of drainage blood from chest tubes was recorded after termination of operation. RESULTS: There were statistical significance between the fibrinogen levels and the drainage (r = -0.897, P < .001). Chest drainage was a mean of 972 mL (range, 240-2445 mL) in the first 48 hours after sternotomy closure. Fibrinogen level and relation to age was statistically significant (P = .015). There was no statistical significance between fibrinogen levels and gender (male gender = 400.7 +/- 123.0 versus female gender = 395.6 +/- 148.1; P = .877) and between drainage and gender (male gender = 968.2 +/- 538.5 versus female gender = 990.0 +/- 554.7; P = .876). Two patients (2%) died early after the surgery. There were no significant differences between the postoperative bleeding and cardiopulmonary bypass time (P = .648) or cross clamp time (P = .974). CONCLUSION: The results of this study suggested that low preoperative fibrinogen level appears to be a useful diagnostic marker to assess the activity of the coagulation system, and that its preoperative level may serve as a potential risk factor for postoperative bleeding after coronary artery bypass surgery. PMID- 17855206 TI - Sternal closure reinforced with rib heads: a novel technique for prevention and treatment of sternal dehiscence. AB - BACKGROUND: When a sternotomy cannot be performed at the midline and/or there is infection at the operation site, sternotomy revision can cause problems that increase the mortality and morbidity of the patients. There is no agreement on the best treatment method. In this paper we present a modified wiring technique. METHODS: This technique consisted of wrapping wires twice around each rib head and placing standard circumferential wire sutures, thus providing full stability by decreasing the load on the sternum using only steel wires. The study group included 23 patients with sternal dehiscence because of inappropriate sternotomy (n = 10) and/or mediastinitis (n = 13). Two mediastinal tubes were placed for irrigation in 13 patients with mediastinitis and/or wound infection, and mobilization and interposition of omentum as an axial graft was performed in 2 patients. Irrigation and antibiotherapy were continued for 4 to 6 weeks. RESULTS: Complete wound healing was obtained in all patients. Twenty-two patients treated with this technique survived. One patient died on postoperative 42nd day because of renal insufficiency and multi-organ failure. CONCLUSION: Early and aggressive debridement of infected and necrotic tissue, irrigation, and antibiotics are necessary for successful treatment, but we believe that the most important factor is full stabilization of the sternal tissue with minimal use of foreign stabilization material. Despite the limited number of cases, we suggest that our stabilization technique seems to be successful in achieving full stabilization even in infected and fragile sternal bony tissue in patients with sternal dehiscence and/or inappropriate sternotomy. PMID- 17855207 TI - Renal function after port access and median sternotomy mitral valve surgery. AB - BACKGROUND: Acute renal injury is an important postoperative complication of mitral valve surgery. We tested the hypothesis that minimally invasive port access (PA) surgery is linked to a smaller postoperative renal injury compared to the standard median Sternotomy (MS) technique. METHODS: Ninety-six patients in the PA group and 102 patients in the MS group were compared regarding postoperative renal dysfunction. Preoperative and maximal postoperative serum creatinine levels were used to calculate creatinine clearance which was implemented for the renal function assessment. Additionally, the new RIFLE classification for acute renal injury was used for the comparison of the postoperative kidney function. This classification is divided into 3 levels and in addition to the glomerular filtration rate, it is also based on urine output. RESULTS: The analysis of preoperative renal function did not demonstrate any significant differences between the two groups in any of the creatinine-based renal function markers. However, the comparison of the minimal postoperative creatinine clearance showed significantly lower values in the median sternotomy group. The conventional MS approach was confirmed as an independent renal risk factor in the multivariate analysis. The postoperative RIFLE classification comparison also showed higher postoperative renal impairment in the MS group. CONCLUSION: With the limitations of a retrospective study, our results suggest that for mitral valve surgery the minimally invasive PA approach might be associated with lower postoperative renal injury compared to the conventional surgical technique. PMID- 17855208 TI - Multiple valve replacement in limited access: a case report. AB - Nowadays minimally invasive surgery represents an accepted technique to treat heart valve disease. We report a case of surgical correction of multiple valve disease in a 61-year-old woman through a minimally invasive right anterolateral minithoracotomy. The intervention was performed under transesophageal echocardiography and videoscopic guidance. High thoracic epidural anesthesia allowed a rapid weaning from mechanical ventilation and a faster recovery. PMID- 17855209 TI - Prophylactic intra-aortic balloon pump is useful to facilitate percutaneous coronary interventions: images from rescue cases. AB - Images are presented of coronary reperfusion that occurred shortly after insertion of an intra-aortic balloon pump for counter-pulsation in 3 patients with acute myocardial infarction refractory to thrombolytic therapy and hemodynamic derangement. It is shown that prophylactic intra-aortic balloon pump use may facilitate percutaneous coronary intervention during acute myocardial infarction and it is useful to provide a visual assessment of myocardial flow restoring. PMID- 17855210 TI - Successful surgical correction of total anomalous systemic venous drainage: a report of 2 cases. AB - Total anomalous systemic venous drainage is a rare malformation and only limited cases have been reported previously. Here we report two cases of total anomalous systemic venous drainage with successful surgical correction. PMID- 17855211 TI - Aorto-innominate fistula by gun-shot injury: a case report. AB - We report an aorto-innominate fistula caused by gun-shot injury. The fistula was diagnosed by aortography and repaired under hypothermic circulatory arrest. PMID- 17855212 TI - Spherical polymer micelles: nanosized reaction vessels? AB - Supramolecular self-assembly techniques have provided a versatile means by which to selectively assemble polymeric molecules into well-defined three-dimensional nanostructures. The stabilization and tailoring of these dynamic nanostructures can be achieved using a range of chemistries to afford functional robust nanoparticles. Many examples of the stabilization, functionalization and application of these nanoparticles have been reported in the literature, and this paper will focus on these areas in the context of their potential application as nanometre-sized reaction vessels. PMID- 17855213 TI - Computing protein infrared spectroscopy with quantum chemistry. AB - Quantum chemistry is a field of science that has undergone unprecedented advances in the last 50 years. From the pioneering work of Boys in the 1950s, quantum chemistry has evolved from being regarded as a specialized and esoteric discipline to a widely used tool that underpins much of the current research in chemistry today. This achievement was recognized with the award of the 1998 Nobel Prize in Chemistry to John Pople and Walter Kohn. As the new millennium unfolds, quantum chemistry stands at the forefront of an exciting new era. Quantitative calculations on systems of the magnitude of proteins are becoming a realistic possibility, an achievement that would have been unimaginable to the early pioneers of quantum chemistry. In this article we will describe ongoing work towards this goal, focusing on the calculation of protein infrared amide bands directly with quantum chemical methods. PMID- 17855214 TI - Modelling interwall interactions in carbon nanotubes: fundamentals and device applications. AB - Carbon nanotubes are the most commonly used 'building blocks' of modern nanotechnology. Their unique mechanical and electronic properties, stability and functionality show great promise in creating functional devices on the nanometre scale. One of the great challenges in using this scale is the ability of physical manipulation of the components, such as their positioning and assembling. Strong correlation between the structure and mechanical interactions of the walls of carbon nanotubes provides self-regulation of their relative motion. This can be further exploited in low-friction and high-stiffness devices. In this paper, we present a condensed overview of the recent progress in fundamental understanding of nanomechanical and nanoelectromechanical behaviour of carbon nanotubes and their applications in nanodevices. PMID- 17855215 TI - Ten years of science in Philosophical Transactions A: with the University Research Fellows. AB - In this brief paper, I review my 10 years as the Editor of the Philosophical Transactions of the Royal Society A. I look at the content of the journal over the years, relating it to a full classification of the physical sciences based on the interests of fellows and research fellows of the Royal Society. I show that the journal has performed well in terms of downloads, citations and impact factors. Innovations such as the Millennium and Christmas Issues for young scientists have stimulated a close and enjoyable interaction with the Society's research fellows. In addition to authoring papers and organizing themes, they have always been keen to help with the refereeing processes. They provided exciting demonstrations for a Summer Science exhibit that I organized to highlight the work of the journal, and five of the research fellows now sit on the Editorial Board. Looking to the future, I describe the new subject clusters that are being introduced as the journal steps up its publication rate from one issue per month to two, starting in January 2008. PMID- 17855216 TI - Chemistry across scales: from molecules to cells. AB - Many important biological functions are strongly dependent on specific chemical interactions. Modelling how the physicochemical molecular details emerge at much larger scales is an active area of research, currently pursued with a variety of methods. We describe a series of theoretical and computational approaches that aim to derive bottom-up descriptions that capture the specificity that ensues from atomistic detail by extracting relevant features at the different scales. The multiscale models integrate the descriptions at different length and time scales by exploiting the idea of mechanical responses. The methodologies bring together concepts and tools developed in seemingly unrelated areas of mathematics such as algebraic geometry, model reduction, structural graph theory and non convex optimization. We showcase the applicability of the framework with examples from protein engineering and enzyme catalysis, protein assembly, and with the description of lipid bilayers at different scales. Many challenges remain as it is clear that no single methodology will answer all questions in such multidimensional complex problems. PMID- 17855217 TI - Advances in solid dosage form manufacturing technology. AB - Currently, the pharmaceutical and healthcare industries are moving through a period of unparalleled change. Major multinational pharmaceutical companies are restructuring, consolidating, merging and more importantly critically assessing their competitiveness to ensure constant growth in an ever-more demanding market where the cost of developing novel products is continuously increasing. The pharmaceutical manufacturing processes currently in existence for the production of solid oral dosage forms are associated with significant disadvantages and in many instances provide many processing problems. Therefore, it is well accepted that there is an increasing need for alternative processes to dramatically improve powder processing, and more importantly to ensure that acceptable, reproducible solid dosage forms can be manufactured. Consequently, pharmaceutical companies are beginning to invest in innovative processes capable of producing solid dosage forms that better meet the needs of the patient while providing efficient manufacturing operations. This article discusses two emerging solid dosage form manufacturing technologies, namely hot-melt extrusion and fluidized hot-melt granulation. PMID- 17855218 TI - Adaptive optics in microscopy. AB - The imaging properties of optical microscopes are often compromised by aberrations that reduce image resolution and contrast. Adaptive optics technology has been employed in various systems to correct these aberrations and restore performance. This has required various departures from the traditional adaptive optics schemes that are used in astronomy. This review discusses the sources of aberrations, their effects and their correction with adaptive optics, particularly in confocal and two-photon microscopes. Different methods of wavefront sensing, indirect aberration measurement and aberration correction devices are discussed. Applications of adaptive optics in the related areas of optical data storage, optical tweezers and micro/nanofabrication are also reviewed. PMID- 17855219 TI - The engineering options for mitigating the climate impacts of aviation. AB - Aviation is a growing contributor to climate change, with unique impacts due to the altitude of emissions. If existing traffic growth rates continue, radical engineering solutions will be required to prevent aviation becoming one of the dominant contributors to climate change. This paper reviews the engineering options for mitigating the climate impacts of aviation using aircraft and airspace technologies. These options include not only improvements in fuel efficiency, which would reduce carbon dioxide (CO2) emissions, but also measures to reduce non-CO2 impacts including the formation of persistent contrails. Integrated solutions to optimize environmental performance will require changes to airframes, engines, avionics, air traffic control systems and airspace design. While market-based measures, such as offset schemes and emissions trading, receive growing attention, this paper sets out the crucial role of engineering in the challenge to develop a 'green air traffic system'. PMID- 17855220 TI - Four-stranded DNA: cancer, gene regulation and drug development. AB - DNA can form many structures other than the famous double helix. In particular, guanine-rich DNA of particular sequences can form four-stranded structures, called G-quadruplexes. This article describes the structural form of these sequences, techniques for predicting which sequences can fold up in this manner and efforts towards stability prediction. It then discusses the biological significance of these structures, focusing on their importance in telomeric regions at the end of chromosomes, and their existence in gene promoters and mRNA, where they may be involved with regulating transcription and translation, respectively. Ligands that are capable of selectively binding to these structures are introduced and described, as are DNA aptamers that form G-quadruplex structures; both of these classes of compound have been investigated as anticancer agents in clinical trials. The growing use of G-quadruplexes in the nanotechnology field is also outlined. The article concludes with an analysis of future directions the field may take, with some proposals for further important studies. PMID- 17855221 TI - Biomimetics for next generation materials. AB - Billions of years of evolution have produced extremely efficient natural materials, which are increasingly becoming a source of inspiration for engineers. Biomimetics-the science of imitating nature-is a growing multidisciplinary field which is now leading to the fabrication of novel materials with remarkable mechanical properties. This article discusses the mechanics of hard biological materials, and more specifically of nacre and bone. These high-performance natural composites are made up of relatively weak components (brittle minerals and soft proteins) arranged in intricate ways to achieve specific combinations of stiffness, strength and toughness (resistance to cracking). Determining which features control the performance of these materials is the first step in biomimetics. These 'key features' can then be implemented into artificial bio inspired synthetic materials, using innovative techniques such as layer-by-layer assembly or ice-templated crystallization. The most promising approaches, however, are self-assembly and biomineralization because they will enable tight control of structures at the nanoscale. In this 'bottom-up' fabrication, also inspired from nature, molecular structures and crystals are assembled with a little or no external intervention. The resulting materials will offer new combinations of low weight, stiffness and toughness, with added functionalities such as self-healing. Only tight collaborations between engineers, chemists, materials scientists and biologists will make these 'next-generation' materials a reality. PMID- 17855222 TI - Diamond at the nanoscale: applications of diamond nanoparticles from cellular biomarkers to quantum computing. AB - Although nanocrystalline diamond powders have been produced in industrial quantities, mainly by detonation synthesis, for many decades their use in applications other than traditional polishing and grinding have been limited, until recently. This paper presents the wide-ranging applications of nanodiamond particles to date and discusses future research directions in this field. Owing to the recent commercial availability of these powders and the present interest in nanotechnology, one can predict a huge increase in research with these materials in the very near future. However, to fully exploit these materials, fundamental as well as applied research is required to understand the transition between bulk and surface properties as the size of particles decreases. PMID- 17855223 TI - Brain architecture: a design for natural computation. AB - Fifty years ago, John von Neumann compared the architecture of the brain with that of the computers he invented and which are still in use today. In those days, the organization of computers was based on concepts of brain organization. Here, we give an update on current results on the global organization of neural systems. For neural systems, we outline how the spatial and topological architecture of neuronal and cortical networks facilitates robustness against failures, fast processing and balanced network activation. Finally, we discuss mechanisms of self-organization for such architectures. After all, the organization of the brain might again inspire computer architecture. PMID- 17855224 TI - Re-engineering cities: a framework for adaptation to global change. AB - Urban areas are expected to continue their rapid growth in the twenty-first century. Globally, cities are major sources of greenhouse gases emissions and their high population densities make them potential focal points of vulnerability to global environmental change. Moreover, their reach, in terms of flows of materials and resources, extends far outside their borders. Evidently, it is no longer tenable to consider urban systems to be static artefacts constructed in a stable environment, nor continue to divorce them from the global context that influences many of the climatic and socio-economic changes within cities. Furthermore, the uncertainty in the future climatic and socio-economic conditions poses significant challenges for planners. A framework is proposed for analysing urban systems with evidence-based tools over extended time scales. This forms the basis of a manifesto for future challenges and research directions for this critical subject area, which ultimately will help engineers and urban planners to better understand the areas for which they are responsible and to develop adaptation strategies that can tackle the challenges posed by long-term global change and lead to more sustainable cities. PMID- 17855225 TI - Soil mechanics: breaking ground. AB - In soil mechanics, student's models are classified as simple models that teach us unexplained elements of behaviour; an example is the Cam clay constitutive models of critical state soil mechanics (CSSM). 'Engineer's models' are models that elaborate the theory to fit more behavioural trends; this is usually done by adding fitting parameters to the student's models. Can currently unexplained behavioural trends of soil be explained without adding fitting parameters to CSSM models, by developing alternative student's models based on modern theories?Here I apply an alternative theory to CSSM, called 'breakage mechanics', and develop a simple student's model for sand. Its unique and distinctive feature is the use of an energy balance equation that connects grain size reduction to consumption of energy, which enables us to predict how grain size distribution (gsd) evolves-an unprecedented capability in constitutive modelling. With only four parameters, the model is physically clarifying what CSSM cannot for sand: the dependency of yielding and critical state on the initial gsd and void ratio. PMID- 17855226 TI - The future of scientific ballooning. AB - This paper gives a brief overview of the historical development of scientific balloons and their capabilities. Furthermore, a recent programme by NASA is introduced that aims to develop balloons capable of carrying payloads of several tonnes to above 99% of the Earth's atmosphere for up to 100 days. It is shown that the currently investigated balloons suffer from instabilities that can be minimized using a different design paradigm for the cutting patterns. Finally, a novel balloon design, similar to the topology of radiolarians, is introduced that is potentially superior to existing designs. PMID- 17855227 TI - The unmet needs of the elderly with diabetes in home health care. AB - The implementation of the Prospective Payment System (PPS) in Medicare home health care has raised concern about health outcomes of elderly patients since its intention is to curb spending. This study examines the unmet needs of older diabetic patients while receiving home health care and post-discharge from home health care (N = 129) in order to explore any effects of PPS on patients' need. The study found that a higher proportion of elders had unmet needs 30 days post discharge compared with while receiving home health care. The specific unmet needs identified by the elderly diabetic patients included social work services, home health aide, homemaker services, and need for medical equipment. The study explores the role of social work to better manage the unmet needs of diabetic elders who live in the community. PMID- 17855228 TI - Employment post-transplant: a biopsychosocial analysis. AB - Employment following renal transplantation has been lower than predicted at the time of the original end-stage renal disease (ESRD) legislation more than 30 years ago. This paper uses the biopsychosocial model to identify predictors of employment for 411 individuals transplanted at a single, large Midwestern academic center. Less than 50% of respondents reported part-time or full-time employment post-transplant. Factors found to predict employment were age at the time of transplant, race, sex, and patient perception of physical functioning. Individuals who were younger when transplanted, Caucasian, and males were more likely to be employed full-time following transplantation as were those who perceived themselves to have a higher level of physical functioning. No biological factors, including serum creatinine, mean arterial pressure (MAP), and diabetic status, were significant predictors of employment. The biopsychosocial model is used to discuss the implications of these findings for post-transplant employment and social work intervention. PMID- 17855229 TI - Contribution of post-transplant social support to the quality of life of transplant recipients. AB - With advances in medicine and pharmacology, post-transplant quality of life (QoL) has become a major concern of researchers. In social work transplant practice, provision of social support towards QoL warrants attention. The purposes of this study were (1) to describe the social support networks of kidney, liver, and pancreas transplant recipients during the post-transplant phase of their recovery, and (2) to examine the correlations between the types and nature of social support networks and the QoL of these transplant recipients. We conducted an exploratory-descriptive study in a US university's transplant clinic. Instruments were the Social Network Map, Adult Self-Image Scale, Sickness Impact Profile, and Quality of Life Index. Descriptive statistics, and correlation analyses were used with a significance level of .05. We observed correlations between concrete and emotional support, and direction, closeness and duration of support, and QoL. Based on our findings, we discussed implications for research and practice. PMID- 17855230 TI - Medical social work practice and SARS in Singapore. AB - This article reports on the findings of a qualitative study exploring the impact of SARS on social work practice in five different hospitals in Singapore. The study sought to examine the range of interventions adopted by 28 medical social workers and the theoretical orientations underpinning them. The findings discussed include the impact of infection control practices on social work intervention, the range of interventions undertaken, respondents' reflections and self-awareness, the role of values and ethics, creativity and training, and their recommendations for future emergencies. While the findings of the study relate specifically to hospital social work practice, the crisis and trauma nature of the work makes it applicable to a broader range of practice in these areas and a range of populations. The findings from this study could also inform the development of training programs for social work and other clinical health workers, and emergency management planning. PMID- 17855231 TI - Hope among terminally ill patients in Singapore: an exploratory study. AB - This study presents an exploration into hope, a source of strength among the terminally ill patients in Singapore. It explores, from the conventionally neglected patients' perspective, their definition of hope, factors that cause changes in their hope and roles that the formal service providers can play to instill hope in patients. All the respondents who participated in this study were diagnosed with terminal cancer and were staying in Dover Park Hospice, a hospice in Singapore for the terminally ill. The results reveal that there is greater diversity in the definition of hope among patients in Singapore compared with the definition given by patients from the studies with a non-Asian sample. Support from people, religion, acceptance of illness, and knowledge of self in better condition as compared with others were four factors found helpful in promoting hope while absence of family members led to a decrease in hope. There were three main roles performed by the formal service providers that were perceived as useful in instilling hope among terminally ill patients. They were that of (1) a care provider, (2) a provider of emotional support, and (3) a wish fulfiller. In the final analysis, the study seems to suggest that spiritual and relational hopes, together with open and honest communication between patients and family members, are very important strengths for Singaporeans diagnosed with advanced illness. PMID- 17855233 TI - Preface. PMID- 17855235 TI - Kinship care:from family tradition to social policy in the african american community. AB - Today, kinship care is equal part family tradition and social welfare policy. This volume explores the balance of the two and presents current practice challenges of formal and informal kinship care. It also addresses the seminal role of grandparents as kinship care providers. doi:10.1300/J045v22n03_01. PMID- 17855236 TI - Future outlook in african american kinship care families. AB - Orientation to the future, in the social science literature, is linked to social adaption and adjustment. This study examines the future outlook in African American kinship care families. The focus of the study was restricted to adolescents in the kinship care population and examined both youth's and parent figure's outlook for the future. Using the National Longitudinal Survey of Youth (NLSY97), the study describes the future orientation of African American youth who live with relative caregivers. It tests for differences in orientation to the future between kinship care parents and those with biological and other family types and tests the hypothesis of there being a significant difference in future orientation between youth and their relative acting as parent caregiver. Findings demonstrate significant variability in the future outlook of African American youth within kinship care families. The findings suggest that social workers and mental health practitioners who work with youth in goal setting behaviors should include the relative caregiver and the family in the counseling process. doi:10.1300/J045v22n03_02. PMID- 17855237 TI - Kinship Care Placement and Children's Academic Performance. AB - Very little consideration has been given to the impact children's living situations can have on their educational performance. The relationship of family environment to the children's educational performance depends in part upon the experiences and intent of the mediating adults who frame, select, focus and interpret the experiences children have in ways that produce an appropriate attitude toward education. Because of changing family patterns, along with significant social and economic factors plaguing many families today, particularly African American families, a substantial number of children continue to grow up in circumstances that put them at risk for unstable family environments, low achievement, and school failure. These unstable family environments often lead to placements in families other than their biological families. Often times these placements are within the state foster care system and for some the placement is with a relative, known as kinship care. Kinship placement is seen as an alternative in maintaining some type of stable family environment for these children at risk. In view of the relatively high incidence of low school performance and other social issues of children at risk, the role of minority families in the education of their children has become a national interest. The issue being addressed in this article centers around specific family processing factors in kinship care environments and its impact on children's academic performance. doi:10.1300/J045v22n03_03. PMID- 17855238 TI - Child Only Kinship Care Cases:The Unintended Consequences of TANF Policies for Families Who Have Health Problems and Disabilities. AB - The passage of the Personal Responsibility Work Opportunities Reconciliation Act (PRWORA) in 1996 changed the way America sought to help its most vulnerable citizens. The Temporary Assistance for Needy Families (TANF) legislation required families to work first. Many families with young children found the stringent requirements of TANF too restrictive for their needs. In this study a number of TANF customers were either physically ill or suffered mental health problems thus preventing them from finding suitable employment. Additionally they may have children who have health problems, which preclude the parent from work activity. Faced with time limits these families may rely on relatives or fictive kin to assume the responsibility of receiving TANF grants for the children so that they may avoid sanctions and possible loss of support for their children. These arrangements are called child-only cases. Given that poverty is related to neglect and neglect may result in out of home placement, these children are at risk for child welfare intervention. Child welfare systems look to kin to assume the responsibility of child rearing to reduce the number of children especially African American children who enter care. However, TANF and informal arrangements for kin to take care of children result in substantially less money for families. An evaluation of TANF is needed to determine if this legislation provides an adequate system for caring for needy families and children. doi:10.1300/J045v22n03_04. PMID- 17855239 TI - Domestic violence and kinship care:connecting policy with practice. AB - Domestic violence is known to have occurred in 40 to 70% of child welfare cases and has served in some capacity as the basis for removing the child from the birth home (Edleson, 1999). Kinship care is regarded as a growing option for many of these families. This conceptual article discusses the distinct ways that kinship care and domestic violence are linked. The authors discuss how silence, the rising incarceration of women, mistrust of the system, difficulty in securing services for survivors, and economic hardship create unique challenges that require attention at both the practice and policy levels. Policy interventions are proposed at the mezzo and macro levels. Recommendations include promoting the Family Violence Options under the TANF program. The article also discusses the unintended consequences the Adoption and Safe Families Act has in domestic violence situations. doi:10.1300/J045v22n03_05. PMID- 17855240 TI - Respite care:outcomes for kinship and non-kinship caregivers. AB - This study reports the outcomes associated with the use of formal respite care services among a sample of kinship, foster and adoptive caregivers of special needs children involved in the child welfare system. It uses pre-post survey research data collection methods to evaluate changes in caregivers' ratings of their quality of life, health, stress, support, objective and subjective burden, stress, and family relations. Caregivers reported reduced stress, improved quality of life, and significantly decreased feelings of objective burden as a result of respite. Suggestions for improving and evaluating respite care outcomes are provided. doi:10.1300/J045v22n03_06. PMID- 17855241 TI - Kinship and spirituality:utilizing strengths of caregivers. AB - Kinship caregivers view spirituality and religion as integral and holistic in nature and an essential coping component to their survival as caregivers. This article examines the following eight spirituality and religious themes defined by a group of African American caregivers of children: spirituality and destiny; spirituality and drugs; faith and healing; spirituality and negotiation; surviving through faith; spirituality, religion, and community; religion; worship and the child; and the need for respite through worshiping and self-care. Historical and social aspects regarding the role of spirituality and religion within the African American community are discussed. Qualitative data from a focus group of 19 low income African American kinship caregivers aged 40-70 years are used to present spiritual and religious clinical tools, techniques, and concepts for intervening with kinship caregivers. doi:10.1300/J045v22n03_07. PMID- 17855242 TI - Biological relatives:forgotten caregivers. AB - The needs of biological relatives can often be overlooked because caseworkers are charged to act in the best interest of the child, meet the demands of foster parents and assume large court and paperwork responsibilities. Using a case study approach of a private therapeutic foster care agency located in Washington, DC, this study examines the needs of biological parents from the perspective of both the biological parents (n = 14) and child welfare workers (n = 14). It also addresses both systemic and personal barriers associated with the engagement and involvement of the biological parent. Findings are that there are varying levels of involvement of the biological parent; however, there is often confusion surrounding engagement practices absent reunification as a goal. This is especially relevant for kinship care where the goal of reunification is sometimes obscured by the placement of children with their families. Policy and practice implications are discussed with an emphasis on increasing the focus on biological relatives in the kinship care network. doi:10.1300/J045v22n03_08. PMID- 17855243 TI - Coping resources:effects on the psychological well-being of african american grandparents raising grandchildren. AB - The impact that parenting responsibilities have on the psychological well-being of African American grandparents raising grandchildren is an increasing concern in American society. Contemporary research studies indicate that African American grandparents who encounter a variety of challenges in raising their grandchildren are able to cope successfully with these situations if they derive a sufficient amount of psychological rewards from raising grandchildren (Giarrusso, Silverstein, & DuFeng, 2000). These rewards include increased gratification, feelings of usefulness, and increasing pride in their own abilities to meet new challenges (Fuller-Thomason & Minkler, 2000). This article will investigate how the coping resource factors of intergenerational solidarity, informal social support and spirituality enhance the psychological well-being of African American grandparents who are raising their grandchildren. doi:10.1300/J045v22n03_09. PMID- 17855244 TI - Grandparents communicating with grandchildren:fostering intergenerational understanding. AB - With the onset of increased longevity, intergenerational relationships are ever more common. These transactions by which persons of different generations interact with one another, are multidimensional and play an important role in family strengths, resilience and solidarity. Using an intergenerational framework this paper explores grandparents' experiences with intergenerational relationships with their grandchildren and discusses strategies for fostering communication and understanding across generations. Feedback from older adults who attend three senior centers provide insight and suggestions for enriching intergenerational communication. doi:10.1300/J045v22n03_10. PMID- 17855245 TI - Grandparents raising grandchildren:kinship care in Baltimore public housing. AB - Life circumstances and threatening ecologies disenfranchise families living in public housing development. Many are children who live with their grandparents in housing units, but are not on the lease. The grandparents and grandchildren experience health problems, are in poverty, and are not served by the child welfare system. Frequently, the children are forced to sleep in bedrooms with other individuals who may be inappropriate, subjecting them to potential sexual child abuse and other circumstances. Housing officials are compelled to remedy this problem and ensure that all residents of public housing are on the lease and are properly housed consistent with the U.S. Housing Act of 1932. National housing policy needs to be reformed to accommodate the needs of children who for a range of circumstances cannot live with their parents. doi:10.1300/J045v22n03_11. PMID- 17855246 TI - Grandfathers raising grandchildren:an exploration of african american kinship networks. AB - Objectives. The purpose of this study was to more fully understand the factors that motivate and influence kinship care provided by African American grandfathers who raise their grandchildren.
Methods. Data were gathered from a community sample of older men, age 65+, who were responsible for the care of at least one grandchild in a rural community in southeastern North Carolina. Fifty-four percent of the grandfathers were African American men who are the focus of the present analysis. Responses were analyzed using a qualitative content analysis mode and descriptive statistics.
Results. Five factors (obligation, lack of availability of other caregivers, family tradition, role modeling, care and concern) that influence their decision to assume the parenting role emerged and three areas (lack of resources, feelings of powerlessness, religious beliefs and spirituality) that impact their ability to continue providing care were identified.
Discussion. Findings indicate that practitioners seeking to understand kinship care and assist grandparents who are raising grandchildren must take into account the hardships these families face due to a lack of concrete services and the implications for mental health. Results affirm the need for special attention to grandfathers who provide kinship care. doi:10.1300/J045v22n03_12. PMID- 17855247 TI - Different pathways to a common destiny:grandparent caregivers in the district of columbia. AB - Nationwide, grandparents raising grandchildren is a growing phenomenon. In the District of Columbia, 19% of children under age 18 live in kincare-headed households. This compares to 8% nationally. This article reports on findings from an AARP focus group study of 40 grandparents raising grandchildren in the District of Columbia. It tells the stories of individuals who have traveled different pathways to arrive at their common destiny of being a grandparent caregiver. It primarily uses the voices of African American grandmothers and grandfathers to address the resources and challenges they face as they care for and care about their grandchildren. Through hearing their stories, AARP crafted nine recommendations aimed at improving the quality of life of District of Columbia grandparents raising grandchildren. The article reports on recommendations emerging from the research and reinforces the need for collaboration among various stakeholders to address the fragmented service delivery system. doi:10.1300/J045v22n03_13. PMID- 17855248 TI - KinNet:A Demonstration Project for a National Support Network for Kinship Care Providers. AB - The KinNET project came into existence because of the need to support a growing number of grandparents and other relatives providing care for children within the foster care system. It was a demonstration project funded by the Children's Bureau designed to create a national network of support groups for older relatives-mostly grandparents-caring for children in and associated with the foster care system. Grandparents and other relatives are an invaluable resource to the child welfare system. However, these caregivers are also an overburdened population that needs creative and supportive interventions to enhance their capacity to provide quality care and reduce the risks to the children. In this intervention the support group approach was tested (a replication of the Brookdale Foundation model with project management from Generations United). Support groups often provide kinship caregivers with access to important emotional and community support, information and referral, relaxation, and respite. This article briefly describes the project, a profile of the caregivers (n = 102) and the children in their care (n = 226), and highlights from the survey data. In addition, we discuss the three key lessons learned from the project and make recommendations to better serve this population. doi:10.1300/J045v22n03_14. PMID- 17855249 TI - Epilogue-kinship care: practice and policy implications. PMID- 17855250 TI - [Progress in the study of histone methyltransferases]. AB - Site- and state-specific lysine methylation of histones is catalyzed by a family of proteins including those contain the evolutionarily conserved SET domain. Research on histone methyltransferases is a part of epigenetics, which plays a fundamental role in heterochromatin formation, X-chromosome inactivation and transcription regulation. Aberrant histone methylation was linked to a number of developmental disorders and human disease including several carcinomas. Histone lysine methylation is a functionally complex process, as it can either activate or repress transcription, depending on sequence-specific lysine methylation site in histones. Non-histone proteins were found to be methylated by SET domain containing histone methyltransferases whose primary targets were presumed to be histones. The researches on histone methyltransferases will make a completely new space for transcriptional activity, embryonic development, cell differentiation, and signal transduction. PMID- 17855251 TI - [DNA methylation and development abnormalities in cloned animals]. AB - Most cloned animals by nuclear transfer were dead before their births, and only a few can develop to their late gestation or adulthood. Although some cloned offsprings can survive, they often have some development disfigurements and abnormal phenotypes in various degrees. DNA methylation is an important modifiable manner of epigenetic dominating the correct expression of gene. It is a main instrument of regulating genome function and plays a prominent part in the embryonic normal development. Through researching the pattern of DNA methylation, we found that there were many abnormal DNA methylation patterns in cloned animals, which might be the primary reasons for inducing premature death of cloned embryos and development abnormalities of cloned animals. This article discusses the function of DNA methylation, the aberrant DNA methylation patterns in cloned animals, and the reasons of inducing abnormal DNA methylation in cloned animals. PMID- 17855252 TI - [Progress on complex vertebral malformation in Holstein cattle]. AB - Complex vertebral malformation (CVM), a lethal autosomal recessive inherited defect in Holstein breed, was newly reported in Demark. If the proportion of CVM carriers in the nucleus breeding group of Holstein is high, great economic losses to dairy industry would be caused by the death of affected homozygous fetuses and the abortion of pregnant cows. The main symptoms and some important influences of CVM to dairy industry were reviewed, The process of researches on the CVM and the testing methods were explicated, and the status of potential CVM carriers in China was also discussed. PMID- 17855253 TI - [Strategies and progresses on cereal comparative genomics]. AB - With the completion of the model plant genome sequencing projects such as Arabidopsis and rice (Oryza sativa L.), comparative genomics has been developed rapidly in recent years. As a new branch of science, this technique has offered a new approach for studying plant genome evolution, structure and function. In this paper, the research strategies, such as comparative genetic mapping, microcollinearity study in gene structure, comparative research on the ESTs and proteins, comparative QTL mapping among crops, and comparative map-based cloning of genes, were summarized. We reviewed the principles, characteristics, feasibilities and progresses of various strategies that were used in plant comparative genomics. It would be helpful to use the sequence data from model plants to elucidate the structure and function of other crop genomes. PMID- 17855254 TI - [Finding finer functions for proteins related to breast cancer based on protein interaction network]. AB - Breast cancer is one of the most common malignant tumours. However, the existing functional knowledge about the proteins related to the breast cancer is too general to promote the following study. To find their finer functions, we suggest using the function-specific interaction sub-networks by integrating the functional knowledge of Gene Ontology and the protein-protein interaction network. The results show that the proposed approach is able to reliably find finer functions for these proteins with high precision. The predicted finer functions are highly valuable for guiding the follow-up wet-lab re-search to study the molecular mechanism of breast cancer. PMID- 17855255 TI - [A novel mutation of PRSS1 gene in a Chinese hereditary pancreatitis family]. AB - We report the identification of a novel mutation in the protease serine 1 (PRSS1) gene in a hereditary pancreatitis (HP) family. Relevant clinical data were collected in this 24-member family. Moreover, the PRSS1 gene was amplified from the genomic DNA of the members with pancreatitis. The amplified products were analyzed by sequencing. A cytosine (C) to thymine (T) mutation in PRSS1 exon3 was detected in four affected members. This novel PRSS1 mutation may be an important factor associated with HP. PMID- 17855256 TI - [Analysis of genetic variations at M857 locus of the a1-Fucosy- trans-ferase (FUT1) ORF in pigs]. AB - Enterotoxigenic Escherichia coli F18 (ETEC F18) is the main pathogen that causes edema disease and post-weaning diarrhea in piglets, and a1-fucosytransferase (FUT1) gene has been identified as a receptor gene encoding the receptor for ETEC F18 bacteria. In this study, the method of PCR-RFLP was used to investigate the among 21 breeds including one wild boar breed and 20 western commercial and Chinese native pig breeds (populations). The results showed that none of the individuals in all 21 breeds possessed the resistant AA genotype, the genetic polymorphisms of the FUT1 locus were only detected in two western pig breeds (Duroc and Yorkshire), Lingao pig and hybrid pig breeds, while the wild boar and all the other Chinese pig breeds only possessed the susceptible GG genotype. The results indicated that Chinese native pig breeds, unlike western pig breeds, lack the genetic background on the resistance to ETEC F18 bacteria. This may be owe to their different origination, as the resistance gene to ETEC F18 might be originated from European wild boar. It was also inferred that edema disease and post-weaning diarrhea caused by ETEC F18 had close relationship with the growth speed of pigs. PMID- 17855258 TI - [Comparative study of SNP diversity and calculation of the effective size of population in chicken]. AB - A region (200 kb) of Contig. 060226.1 on GGA1 was selected to study the average diversity of Red Jungle Fowl (RJF), Taihe Silk chicken (TS), and White Recessive Rock (WRR), and estimate the effective population size (Ne) of chicken. The mean heterozygosities of RJF, TS and WRR were 0.28533+/-0.034747, 0.32926+/-0.039191 and 0.30168+/-0.040382, respectively. Significant test indicted that there is not significant difference between them (P=0.2368>0.05). The initial chicken effective population size was estimated to be about 20 000-150 000. Chicken has undergone serious population bottleneck effect during the first stage of domestication. However, this bottleneck effect did not result in a substantial loss of diversity as revealed by SNP. The possible explanations for similar SNP diversity between domesticated chicken and Red Jungle Fowl might due to many factors, such as a big Ne in earlier phase of domestication, population expending in breed differentiation, abroad crossing between breeds (especially crossing with RJF), together with high recombination rate in chicken genome. PMID- 17855257 TI - [Association of variations in MyoD family of genes with body measurement traits in goat]. AB - Single nucleotide polymorphisms (SNPs) of hircine myf-5, myf-6 genes and 5'flanking region of the myoD gene (myoD 5') were analyzed by PCR-SSCP in Boer goat and Xuhuai white goat. Three genotypes were found at the myf-5 locus of Xuhuai white goat, denoted AA, AB and BB, while all of Boer goats were of AA genotype. Only AA and AB genotypes were found at myf-6 and myoD 5' loci. The effects of genotypes of myf-5, myf-6 and myoD 5'flanking region loci on body measurement traits were estimated. The results showed that genotypes at the myf-5 locus were significantly associated with hucklebone width and hucklebone width index in Xuhuai white goat (P<0.05). Genotypes at the myf-6 locus were significantly associated with withers heights and hucklebone width index in Boer goat (P<0.05), but no significant associations were found for any traits in Xuhuai white goat. The myoD 5' locus was not significantly associated with any traits in both types of goat. PMID- 17855259 TI - [Correlation analysis of relationships between polymorphisms of high quality chicken myogenin gene and slaughter and meat quality traits]. AB - PCR-SSCP technique was designed in this study to investigate the effect of MyoG on quality meat chicken (developed by Sichuan Dahen Poultry Breeding Company using local breeds). Four mutations at base position in promoter were detected among individuals in each line, i.e. T/C in locusA and T/A, T/C and A/G in locus B . The least square analysis showed that there were a significant difference between genotypes and breast muscle percentage and some carcass traits (P<0.05for locus A. There were a significant difference (P <0.05) in breast muscle weight between ACAA and AB geno- types; a significant difference (P <0.05) in leg muscle percentage between CC and AC for locus B, and a extremity signifi-cant difference (P <0.01) in the frequency of genotype muscle Fibre Density for Bothlocus A to locus B. There was no sig-nificant difference (P >0.05) in the other triats. It was concluded from the results that MyoG gene is the major gene affect-ing the muscle fiber traits of chicken or it links with the candidate gene, and the mutation could be used as the molecular genetic marker to select the chickens for Meat Quality traits. PMID- 17855260 TI - [Cloning and structural analysis of MLP in the silkworm, Bombyx mori]. AB - The LIM domain is found in a wide variety of eukaryotic proteins that regulate gene expression and cell differentiation during development. Muscle LIM protein (MLP) gene in Bombyx mori has been cloned by blasting its EST database and PCR test in present report. The resulting sequence covers 2 327 bp of cDNA (GenBank accession No. DQ311195). It has a complete open reading fragment and encodes a 494 amino acid protein. Genomic DNA sequence contains 11 exons and 10 introns, with intron splicing following the GT-AG rule. M.W. and PI of the predicted MLP in Bombyx mori are 53.03 kDa and 8.29 respectively. A single LIM domain linked to a glyscine-rich region is found in a previously deposited LIM protein (AAR23823) in Bombyx mori. MLP identified in this report encodes a protein with five tandem LIM-glycine modules. The two LIM proteins could be produced by alternative splicing and both are probably involved in muscle cell differentiation. This work provides foundation for further research on the in vivo function of MLP. PMID- 17855261 TI - [Analysis on the genetic structure of 8 Asia buffalo populations]. AB - One hundred and forty seven alleles were detected when thirteen microsatellite loci were analyzed applying fluorescence-multiplex PCR technology in eight buffalo populations were analyzed, including six indigenous Chinese native breeds (DechangXinglongFuzhongWenzhouDongliuFu'an), and two introduced breeds (MurrahNili-Ravi). Seven populations have their own unique alleles, total number is twenty-three. As to all the eight populations, effective number of alleles (Ne) was between 2.2908 and 4.2308, heterozygosity (H) between 0.4951 and 0.7194, and polymorphism information content (PIC) between 0.4495 and 0.6776. Eleven of the thirteen microsatellite loci were of high polymorphism and were then the appropriate, polymorphism marker could be used to analyze properly genetic diversity of the involved buffalo populations. Cluster analysis indicated that Fuzhong and Dongliu were clustered together, then with an independent cluster of Xinglong. Wenzhou and Fu'an were clustered together, Dechang was an independent cluster. Murrah and Nili-Ravi were clustered together. PMID- 17855262 TI - [Comparison of genetic linkage maps based on F2F6 populations derived from rice subspecies cross]. AB - A F2 population containing 180 lines, which was derived from the cross between the partially sequenced indica variety "Pei'ai 64S" and the completely sequenced japonica variety "Nipponbare" , was used to construct a genetic linkage framework map (referred to as F2 map), which included 138 microsatellite sites and covered 1737.81 cM of total genomic length, an average distance of 11.90 cM. Single seed descent F2:6 population with 330 lines was used to construct a genetic linkage map (known as F6 map) using 92 markers. The total genomic length and average distance were 2563.5 cM and 27.86 cM, respectively. The F2 and F6 maps differed in linkage groups, mapped markers, sequenced order of markers, ge-netic distance and average distance on the maps. Preliminary analysis about these difference was carried out. PMID- 17855263 TI - [Genetic analysis and gene mapping of cold-induced seedling chlorosis in rice]. AB - We found that the seedlings of indica rice cultivar Dular showed chlorosis but the seedlings of japonica rice cultivar Lemont remained green under natural low temperature in early spring. Using an F2 population of Lemont Dular, we found that the difference of cold tolerance at seedling stage between Dular and Lemont is controlled by a single major gene, with the chlorosis allele being recessive. We named the gene cisc(t). With the help of SSR markers, cisc(t) was mapped in a 5.5 cM interval between SSR markers RM257 and RM242 on chromosome 9. PMID- 17855264 TI - [Distribution of 45S rDNA sequence on chromosomes of Triticum aes-tivum and its relative species]. AB - Fluorescent in situ hybridization (FISH) and sequential C-banding and FISH techniques were used in locating 45S rDNA sequence on specific chromosomes of Triticum monococcum, T. dicoccoides, T. aestivum, Hordeum vulgare, Haynaldia villosa, T. durum-Haynaldia villosa amphiploid, Avena fatus, and Roegneria kamoji. High polymorphism between common wheat and its relatives on 45S rDNA sequence distribution was detected. All the chromosomal secondary constriction regions of these species had 45S rDNA loci. Some non-satellite chromosomes had additional 45S rDNA loci. A 45S rDNA locus was located on the terminal region of the short arm of R. kamoji chromosome 1Rk#1. PMID- 17855265 TI - [Construction of a SSR linkage map and mapping of quantitative trait loci (QTL) for leaf angle and leaf orientation with an elite maize hybrid]. AB - Maize (Zea mays L.) breeders have begun selecting for more compact plants for higher density planting in order to increase yield per unit area. Leaf angle and leaf orientation are very important traits affecting maize plant type (compactness). In this study, a genetic linkage map containing 138 simple sequence repeat (SSR) markers was constructed based on a mapping population consisting of 500 F2 individuals from the cross between inbred lines Ye478 and Dan340. This SSR linkage map spans a total of 1 394.9 cM with an average interval of 10.1 cM. Quantitative trait loci (QTL) for leaf angle and leaf orientation were identified in 397 F2:3 families. Six QTL for leaf angle were detected that could explain 41.0% of the phenotypic variation; while, eight QTL were detected for leaf orientation that could explain 60.8% of the phenotypic varia-tion. Single QTL contribution to phenotypic variation ranged from 2.9% to 13.6%. Additive and partial dominance were the main genetic effects for leaf angle and leaf orientation; in addition, nine pairs of locus interactions were detected for the two traits, indicating that epistatic interactions at the two-loci level also play a measurable role in the genetic basis of the two traits. PMID- 17855266 TI - [Mapping insect resistance QTLs of soybean with RIL population]. AB - A recombinant inbred line (RIL) population, NJRIKY, which was derived from the cross Kefeng 1 xNannong 1138-2, was used to constructed the genetic linkage map. Larval weight and pupae weight of cotton worm [Prodenia litura (L.) Fabricius] were examined and used as indicators of resistance. Based on the linkage map constructed with SSR markers of this RIL population, one QTL responsible for larval weight was mapped on linkage group G20-O and the position was 31.91 cM. The QTL's additive effect was 0.0408 and explained 11.74 of the total variation of the larval weight. Two QTLs associated with pupae weight were mapped on linkage group G8-D1b+W and G17-L and the positions were 14.71 cM and 0.01 cM, respectively. The QTLs' additive effects were -0.0139 and 0.0103 ,which explained 11.30 and 6.36 of the total variation of larval weight, respectively. PMID- 17855267 TI - [Drought resistance and heredity of transgenic tobacco with OsMAPK4 gene]. AB - OsMAPK4 gene was obtained by RT-PCR using gene special primer from Liaoyan241 leaf treated with low temperature. Plant expression vector pBME12 was constructed in which OsMAPK4 gene was regulated by E12 promoter. OsMAPK4 gene was transferred into tobacco via Agrobacterium-mediated method and 25 transgenic plants obtained. The results of drought resistance experiments showed that overexpression of OsMAPK4 gene conferred enhanced drought resistance of T1 transgenic plants. Kanamycin-resistance segregation in T1 transgenic plants showed that the most transgenic lines were in single gene inheritance. PMID- 17855268 TI - [Genetic model analysis of leaf-weight traits in non-heading Chinese cabbage (Brassica campestris ssp. chinensis Makino)]. AB - The mixed major-gene plus polygene inheritance model was used to analyze the genetics of leafblade-weight and petiole-weight trait in SIxQiu017 of non-heading Chinese cabbage. The results showed that the leafblade-weight trait was controlled by one pair of negative complete dominant major genes plus additive dominant polygene (D-4). The additive effect in the major gene was 1.8991, the dominant effect was -1.8991; the additive effect in the polygene was -1.2934, and the dominant effect was 1.7933; the potential ratio was -1.3865, and the dominant degree was -1.0000; the heritability of the major gene was 6.98% in B1 generation, 4.33% in B2 generation, and 36.08% in F2 generation; the heritability of the polygene was 16.03% in B1 generation, 7.39% in B2 generation, and 23.96% in F2 in the leafblade-weight trait. The peti-ole-weight trait in SIxQiu017 was controlled by one pair of additive major genes plus additive-dominant polygene (D 2). The additive effect in major gene was -1.1457, the dominant effect was 0.0000; the additive effect in polygene was 1.3472, and the dominant effect was 2.5788. The potential ratio was 1.9142, and the dominant degree was 0.0000; the heritability of the major gene was 31.72% in B1 generation, 5.27% in B2 generation, and 57.94% in F2 generation. The heritability of the polygene was 0.42% in B1 generation, 4.59% in B2 generation, and 4.80% in F2 in the petiole weight trait. The improve-ment of leaf-weight trait of SIxQiu017 should be selected in late generation, and the improvement of petiole-weight trait of SIxQiu017 should be selected in early generation. PMID- 17855269 TI - [Analysis of simple sequence repeats in genomes of Sclerotinia sclerotiorum and Botrytis cinerea]. AB - Simple sequence repeats or microsatellites have been used as genetic markers in population genetics because of their abundance and length variation between different individuals. This study examined the SSRs in the completely sequenced Sclerotinia sclerotiorum and Botrytis cinerea genomes. The occurrences, relative abundance, relative density, most common motifs, and the longest SSRs in the two species were analyzed, and compared with other plant pathogenic fungal species, such as Fusarium graminearum, Magnaporthe grisea and Ustilago maydis. The results demonstrated that the SSRs are abundant in S. sclerotiorum and B. cinerea genomes, and 6 539 and 8 627 SSRs were obtained from these species. The types and distributions of SSRs have similarities between the two species. In the genomes of S. sclerotiorum and B. cinerea, tetra-, penta- and hexa-nucleotide repeats were more abundant than other species, indicating high mutation rates in these species. Furthermore, the abundance and relative density of SSRs were not influenced by the genome sizes and GC content. The analysis in this study provided useful information on applications of microsatellites in population genetics of S. sclerotiorum and B. cinerea. PMID- 17855270 TI - Changing incident diabetes regimens: a Veterans Administration cohort study from 2000 to 2005. PMID- 17855271 TI - Amino-terminal brain natriuretic peptide is related to the presence of diabetic polyneuropathy independently of cardiovascular disease. PMID- 17855272 TI - An accurate risk score based on anthropometric, dietary, and lifestyle factors to predict the development of type 2 diabetes: response to Schulze et al. PMID- 17855274 TI - An accurate risk score based on anthropometric, dietary, and lifestyle factors to predict the development of type 2 diabetes: response to Schulze et al. PMID- 17855276 TI - Circulating retinol-binding protein-4, insulin sensitivity, insulin secretion, and insulin disposition index in obese and nonobese subjects: response to Broch et al. PMID- 17855278 TI - Insulin resistance, dyslipidemia, and cardiovascular disease. PMID- 17855279 TI - Diabetic foot infections: microbiology made modern? Array of hope. PMID- 17855280 TI - Cancer risk among users of oral contraceptives: cohort data from the Royal College of General Practitioner's oral contraception study. AB - OBJECTIVE: To examine the absolute risks or benefits on cancer associated with oral contraception, using incident data. DESIGN: Inception cohort study. SETTING: Royal College of General Practitioners' oral contraception study. PARTICIPANTS: Directly standardised data from the Royal College of General Practitioners' oral contraception study. MAIN OUTCOME MEASURES: Adjusted relative risks between never and ever users of oral contraceptives for different types of cancer, main gynaecological cancers combined, and any cancer. Standardisation variables were age, smoking, parity, social class, and (for the general practitioner observation dataset) hormone replacement therapy. Subgroup analyses examined whether the relative risks changed with user characteristics, duration of oral contraception usage, and time since last use of oral contraception. RESULTS: The main dataset contained about 339,000 woman years of observation for never users and 744,000 woman years for ever users. Compared with never users ever users had statistically significant lower rates of cancers of the large bowel or rectum, uterine body, and ovaries, tumours of unknown site, and other malignancies; main gynaecological cancers combined; and any cancer. The relative risk for any cancer in the smaller general practitioner observation dataset was not significantly reduced. Statistically significant trends of increasing risk of cervical and central nervous system or pituitary cancer, and decreasing risk of uterine body and ovarian malignancies, were seen with increasing duration of oral contraceptive use. Reduced relative risk estimates were observed for ovarian and uterine body cancer many years after stopping oral contraception, although some were not statistically significant. The estimated absolute rate reduction of any cancer among ever users was 45 or 10 per 100,000 woman years, depending on whether the main or general practitioner observation dataset was used. CONCLUSION: In this UK cohort, oral contraception was not associated with an overall increased risk of cancer; indeed it may even produce a net public health gain. The balance of cancer risks and benefits, however, may vary internationally, depending on patterns of oral contraception usage and the incidence of different cancers. PMID- 17855281 TI - Risk of cancer and the oral contraceptive pill. PMID- 17855282 TI - Effect of prolonged and exclusive breast feeding on risk of allergy and asthma: cluster randomised trial. AB - OBJECTIVE: To assess whether exclusive and prolonged breast feeding reduces the risk of childhood asthma and allergy by age 6.5 years. DESIGN: Cluster randomised trial. SETTING: 31 Belarussian maternity hospitals and their affiliated polyclinics. PARTICIPANTS: A total of 17,046 mother-infant pairs were enrolled, of whom 13,889 (81.5%) were followed up at age 6.5 years. INTERVENTION: Breastfeeding promotion intervention modelled on the WHO/UNICEF baby friendly hospital initiative. MAIN OUTCOME MEASURES: International study of asthma and allergies in childhood (ISAAC) questionnaire and skin prick tests of five inhalant antigens. RESULTS: The experimental intervention led to a large increase in exclusive breast feeding at 3 months (44.3% v 6.4%; P<0.001) and a significantly higher prevalence of any breast feeding at all ages up to and including 12 months. The experimental group had no reduction in risks of allergic symptoms and diagnoses or positive skin prick tests. In fact, after exclusion of six sites (three experimental and three control) with suspiciously high rates of positive skin prick tests, risks were significantly increased in the experimental group for four of the five antigens. CONCLUSIONS: These results do not support a protective effect of prolonged and exclusive breast feeding on asthma or allergy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN37687716 [controlled trials.com]. PMID- 17855283 TI - Objectively monitored patching regimens for treatment of amblyopia: randomised trial. AB - OBJECTIVES: To compare visual outcome in response to two prescribed rates of occlusion (six hours a day and 12 hours a day). DESIGN: Unmasked randomised trial. SETTING: Research clinics in two London hospitals. PARTICIPANTS: 97 children with a confirmed diagnosis of amblyopia associated with strabismus, anisometropia, or both. INTERVENTIONS: 18 week period of wearing glasses (refractive adaptation) followed by occlusion prescribed ("patching") for six or 12 hours a day. MAIN OUTCOME MEASURES: Visual acuity measured by logMAR letter recognition; objectively monitored rate of occlusion (hours a day). RESULTS: The mean age of children at study entry was 5.6 (SD 1.5) years. Ninety were eligible for occlusion but 10 dropped out in this phase, leaving 80 children who were randomised to a prescribed dose rate of six (n=40) or 12 (n=40) hours a day. The mean change in visual acuity of the amblyopic eye was not significantly different (P=0.64) between the two groups (0.26 (95% confidence interval 0.21 to 0.31) log units in six hour group; 0.24 (0.19 to 0.29) log units in 12 hour group). The mean dose rates (hours a day) actually received, however, were also not significantly different (4.2 (3.7 to 4.7) in six hour group v 6.2 (5.1 to 7.3) in 12 hour group; P=0.06). The visual outcome was similar for those children who received three to six hours a day or more than six to 12 hours a day, but significantly better than that in children who received less than three hours a day. Children aged under 4 required significantly less occlusion than older children. Visual outcome was not influenced by type of amblyopia. CONCLUSIONS: Substantial (six hours a day) and maximal (12 hours a day) prescribed occlusion results in similar visual outcome. On average, the occlusion dose received in the maximal group was only 50% more than in the substantial group and in both groups was much less than that prescribed. Younger children required the least occlusion. TRIALS REGISTRATION: Clinical Trials NCT00274664. PMID- 17855284 TI - Child-parent screening for familial hypercholesterolaemia: screening strategy based on a meta-analysis. AB - OBJECTIVE: To develop a population screening strategy for familial hypercholesterolaemia. DESIGN: Meta-analysis of published data on total and low density lipoprotein (LDL) cholesterol in people with and without familial hypercholesterolaemia according to age. Thirteen studies reporting on 1907 cases and 16 221 controls were used in the analysis. Included studies had at least 10 cases and controls with data on the distribution of cholesterol in affected and unaffected individuals. MAIN OUTCOME MEASURES: Detection rates (sensitivity) for specified false positive rates (0.1%, 0.5%, and 1%) in newborns and in age groups 1-9, 10-19, 20-39, 40-59, and > or =60 years. RESULTS: Serum cholesterol concentration discriminated best between people with and without familial hypercholesterolaemia at ages 1-9, when the detection rates with total cholesterol were 88%, 94%, and 96% for false positive rates of 0.1%, 0.5%, and 1%. The results were similar with LDL cholesterol. Screening newborns was much less effective. Once an affected child is identified, measurement of cholesterol would detect about 96% of parents with the disorder, using the simple rule that the parent with the higher serum cholesterol concentration is the affected parent. CONCLUSIONS: The proposed strategy of screening children and parents for familial hypercholesterolaemia could have considerable impact in preventing the medical consequences of this disorder in two generations simultaneously. PMID- 17855285 TI - Problems with performance related pay in primary care. PMID- 17855286 TI - Dealing with scientific misconduct. PMID- 17855287 TI - Direct to consumer advertising of drugs in Europe. PMID- 17855288 TI - NICE behaviour: QALYs in the community. PMID- 17855289 TI - Spotting the sick child: Face to face always. PMID- 17855290 TI - Spotting the sick child: Video clip is worth 1000 words. PMID- 17855292 TI - Job for life: Satan what done it. PMID- 17855293 TI - Time to drop eponyms: Curbing Medicalese is the issue. PMID- 17855294 TI - NICE behaviour: ME guideline is unworkable. PMID- 17855295 TI - Record investment in NHS fails to improve productivity, Wanless finds. PMID- 17855296 TI - Primary care pays only "lip service" to clinical governance, MPs say. PMID- 17855297 TI - US medical authorities are accused of failing to act over doctors in Guantanamo. PMID- 17855298 TI - Genome sequence of one individual is published for first time. PMID- 17855299 TI - Teen suicide rate rises as prescribing of SSRIs falls, study finds. PMID- 17855300 TI - Europe witnesses first local transmission of chikungunya fever in Italy. PMID- 17855303 TI - Two thirds favour organ donation, but only one in 20 take steps to facilitate it. PMID- 17855307 TI - Congressional staff are briefed on methamphetamine. PMID- 17855308 TI - Israel's anaesthetists protest at plan to expand role of nurses. PMID- 17855310 TI - Hospital closures: the great taboo. PMID- 17855319 TI - Improving health through wealth. PMID- 17855320 TI - The blind leading the blind. PMID- 17855322 TI - Cosmetic surgery gets under Dutch skin. PMID- 17855323 TI - Tackling therapeutic inertia: role of treatment data in quality indicators. PMID- 17855324 TI - Calculate the QT interval in patients taking drugs for dementia. PMID- 17855325 TI - Adult coeliac disease. PMID- 17855326 TI - A painful hip. PMID- 17855332 TI - Screening and brief intervention targeting risky drinkers in Danish general practice--a pragmatic controlled trial. AB - AIMS: Recommendations for routine alcohol screening and brief counselling intervention in primary health care rest on results from intervention efficacy studies. By conducting a pragmatic controlled trial (PCT), we aimed at evaluating the effectiveness of the WHO recommendations for screening and brief intervention (SBI) in general practice. METHODS: A randomized PCT (brief counselling intervention vs no intervention) involving 39 Danish general practitioners (GPs). Systematic screening of 6897 adults led to inclusion of 906 risky drinkers, and research follow-up on 537 of these after 12-14 months. Outcome measures focused on patients' acceptance of screening and intervention and their self-reported alcohol consumption. RESULTS: Patient acceptance of screening and intervention 10.3% (N = 794) of the target population (N = 7, 691) explicitly refused screening. All intervention group subjects (N = 442) were exposed to an instant brief counselling session while only 17.9% of them (79/442) attended a follow-up consultation that was offered by their GP. Consumption Changes At one-year follow up, average weekly consumption had increased by 0.7 drinks in both comparison groups. As secondary findings, we observed an indiscriminate absolute risk reduction (ARR = 0.08 (95% CI: -0.02; 0.18)) in male binge drinking, but adverse intervention effects for women on the secondary outcomes (binge drinking ARR = 0.30 (95% CI: -0.47; -0.09)). CONCLUSIONS: The results of brief interventions in everyday general practice performed on the basis of systematic questionnaire screening may fall short of theoretical expectations. When applied to non selected groups in everyday general practice SBI may have little effect and engender diverse outcome. Women may be more susceptible to defensive reactions than men. PMID- 17855333 TI - Brain atrophy in alcoholics: relationship with alcohol intake; liver disease; nutritional status, and inflammation. AB - OBJECTIVES: Brain atrophy is a common finding in alcoholics. Several mechanisms may be involved, including ethanol itself, malnutrition, liver failure, and, possibly, ethanol-induced hormone and cytokine changes. The aim of this study was to analyse the relation of brain atrophy-assessed by computerized tomography (CT) scan-and the aforementioned alterations. METHODS: Serum insulin-like growth factor 1 (IGF-1), interleukin (IL)-6, IL-8, IL-10, TNF alpha, PTH, estradiol, free testosterone, and corticosterone were measured in 36 alcoholics, ten of them cirrhotics, who also underwent brain CT, which recorded the presence of cortical atrophy or cerebellar atrophy, Evan's, Huckmann's, cella media, bicaudate, cortical atrophy, bifrontal, and ventricular indices, and diameter of the third ventricle; subjective nutritional assessment, midarm anthropometry, and evaluation of liver function. RESULTS: Patients showed marked alterations of all the CT indices compared with 12 controls, but poor relations between these indices and the other parameters analysed (IGF-1, handgrip strength and years of addiction with bifrontal index (P < 0.025 in all cases); PTH and Evan's index (r = 0.36, P = 0.032); mean corpuscular volume with cella index and cortical atrophy (P < 0.05). Cerebellar atrophy was associated with a greater daily ethanol consumption (t = 2.19, P = 0.034). CONCLUSION: Brain atrophy is frequently observed in alcoholics, but relationships with liver function, cytokines, nutritional status, and hormone levels are poor. PMID- 17855334 TI - Concurrent validity of the alcohol use disorders identification test (AUDIT). AB - AIMS: To determine cut-offs for the Alcohol Use Disorders Identification Test (AUDIT) 10-item questionnaire, differentiating hazardous drinking (HZD) and alcohol use disorders (AUD) from low risk drinking (LRD), and AUD from HZD and LRD among married men in a Sri Lankan sample. METHODS: Using 62 low risk drinkers and 88 each from hazardous drinkers and AUD, the AUDIT instrument was compared with adapted and translated versions of a beverage-specific, quantity-frequency questionnaire, and the alcohol use module of the Composite International Diagnostic Interview (CIDI), and two receiver operating characteristic (ROC) curves were plotted. RESULTS: The area under the ROC curves to differentiate HZD + AUD from LRD and AUD from HZD + LRD were 0.96 (95% CI: 0.94-0.99) and 0.97 (95% CI: 0.95-0.99) respectively. The cut-off values of 7 and 16 were observed to have the best trade-offs between sensitivity, specificity, the ratio of positive likelihood to negative likelihood ratios, and positive predictive values. CONCLUSION: The AUDIT could be used to screen for LRD, HZD, and AUD among Sinhalese married men in Sri Lanka. PMID- 17855335 TI - Phenoloxidase is an important component of the defense against Aeromonas hydrophila Infection in a crustacean, Pacifastacus leniusculus. AB - The melanization cascade, in which phenoloxidase is the terminal enzyme, appears to play a key role in recognition of and defense against microbial infections in invertebrates. Here, we show that phenoloxidase activity and melanization are important for the immune defense toward a highly pathogenic bacterium, Aeromonas hydrophila, in the freshwater crayfish, Pacifastacus leniusculus. RNA interference-mediated depletion of crayfish prophenoloxidase leads to increased bacterial growth, lower phagocytosis, lower phenoloxidase activity, lower nodule formation, and higher mortality when infected with this bacterium. In contrast, if RNA interference of pacifastin, an inhibitor of the crayfish prophenoloxidase activation cascade, is performed, it results in lower bacterial growth, increased phagocytosis, increased nodule formation, higher phenoloxidase activity, and delayed mortality. Our data therefore suggest that phenoloxidase is required in crayfish defense against an infection by A. hydrophila, a highly virulent and pathogenic bacterium to crayfish. PMID- 17855336 TI - CD4 interacts constitutively with multiple CCR5 at the plasma membrane of living cells. A fluorescence recovery after photobleaching at variable radii approach. AB - The entry of human immunodeficiency virus into target cells requires successive interactions of the viral envelope glycoprotein gp120 with CD4 and the chemokine receptors CCR5 or CXCR4. We previously demonstrated, by Forster resonance energy transfer experiments, the constitutive association of CD4 and CCR5 at the surface of living cells. We therefore speculated that this interaction may correlate with compartmentalization of CD4 and CCR5 within the plasma membrane. Here, we characterize the lateral distribution, the dynamics, and the stoichiometry of these receptors in living cells stably expressing CD4 and/or CCR5 by means of fluorescence recovery after photobleaching at variable radii experiments. We found that (i) these receptors expressed alone are confined into 1-microm-sized domains, (ii) CD4-CCR5 associations occur outside and inside smaller domains, and (iii) these interactions involve multiple CCR5 molecules per CD4. PMID- 17855337 TI - Granzyme B-induced cell death involves induction of p53 tumor suppressor gene and its activation in tumor target cells. AB - In this study we investigated the involvement of p53 in cytotoxic T-lymphocyte (CTL)-induced tumor target cell killing mediated by the perforin/granzymes pathway. For this purpose we used a human CTL clone (LT12) that kills its autologous melanoma target cells (T1), harboring a wild type p53. We demonstrated initially that LT12 kills its T1 target in a perforin/granzymes-dependent manner. Confocal microscopy and Western blot analysis indicated that conjugate formed between LT12 and T1 resulted in rapid cytoplasmic accumulation of p53 and its activation in T1 target cells. Cytotoxic assay using recombinant granzyme B (GrB) showed that this serine protease is the predominant factor inducing such accumulation. Furthermore, RNA interference-mediated lowering of the p53 protein in T1 cells or pifithrin-alpha-induced p53-specific inhibition activity significantly decreased CTL-induced target killing mediated by CTL or recombinant GrB. This emphasizes that p53 is an important determinant in granzyme B-induced apoptosis. Our data show furthermore that when T1 cells were treated with streptolysin-O/granzyme B, specific phosphorylation of p53 at Ser-15 and Ser-37 residues was observed subsequent to the activation of the stress kinases ataxia telangiectasia mutated (ATM) and p38K. Treatment of T1 cells with pifithrin-alpha resulted in inhibition of p53 phosphorylation at these residues and in a significant decrease in GrB-induced apoptotic T1 cell death. Furthermore, small interference RNAs targeting p53 was also accompanied by an inhibition of streptolysin-O/granzyme B-induced apoptotic T1 cell death. The present study supports p53 induction after CTL-induced stress in target cells. These findings provide new insight into a potential role of p53 as a component involved in the dynamic regulation of the major pathway of CTL-mediated cell death and may have therapeutic implications. PMID- 17855338 TI - N-glycan processing deficiency promotes spontaneous inflammatory demyelination and neurodegeneration. AB - Multiple sclerosis (MS) is characterized by inflammatory demyelination of axons and neurodegeneration, the latter inadequately modeled in experimental autoimmune encephalomyelitis (EAE). Susceptibility of inbred mouse strains to EAE is in part determined by major histocompatibility complex haplotype; however, other molecular mechanisms remain elusive. Galectins bind GlcNAc-branched N-glycans attached to surface glycoproteins, forming a molecular lattice that restricts lateral movement and endocytosis of glycoproteins. GlcNAc branching negatively regulates T cell activity and autoimmunity, and when absent in neurons, induces apoptosis in vivo in young adult mice. We find that EAE susceptible mouse strains PL/J, SJL, and NOD have reduced GlcNAc branching. PL/J mice display the lowest levels, partial deficiencies in N-acetylglucosaminyltransferase I, II, and V (i.e. Mgat1, -2, and -5), T cell hyperactivity and spontaneous late onset inflammatory demyelination and neurodegeneration; phenotypes markedly enhanced by Mgat5(+/-) and Mgat5(-/-) backgrounds in a gene dose-dependent manner. Spontaneous disease is transferable and characterized by progressive paralysis, tremor, dystonia, neuronophagia, and axonal damage in both demyelinated lesions and normal white matter, phenocopying progressive MS. Our data identify hypomorphic Golgi processing as an inherited trait that determines susceptibility to EAE, provides a unique spontaneous model of MS, and suggests GlcNAc-branching deficiency may promote T cell-mediated demyelination and neurodegeneration in MS. PMID- 17855339 TI - NAD kinase levels control the NADPH concentration in human cells. AB - NAD kinases (NADKs) are vital, as they generate the cellular NADP pool. As opposed to three compartment-specific isoforms in plants and yeast, only a single NADK has been identified in mammals whose cytoplasmic localization we established by immunocytochemistry. To understand the physiological roles of the human enzyme, we generated and analyzed cell lines stably deficient in or overexpressing NADK. Short hairpin RNA-mediated down-regulation led to similar (about 70%) decrease of both NADK expression, activity, and the NADPH concentration and was accompanied by increased sensitivity toward H(2)O(2). Overexpression of NADK resulted in a 4-5-fold increase in the NADPH, but not NADP(+), concentration, although the recombinant enzyme phosphorylated preferentially NAD(+). Surprisingly, NADK overexpression and the ensuing increase of the NADPH level only moderately enhanced protection against oxidant treatment. Apparently, to maintain the NADPH level for the regeneration of oxidative defense systems human cells depend primarily on NADP-dependent dehydrogenases (which re reduce NADP(+)), rather than on a net increase of NADP. The stable shifts of the NADPH level in the generated cell lines were also accompanied by alterations in the expression of peroxiredoxin 5 and Nrf2. Because the basal oxygen radical level in the cell lines was only slightly changed, the redox state of NADP may be a major transmitter of oxidative stress. PMID- 17855340 TI - Epithelial-derived fibronectin expression, signaling, and function in intestinal inflammation. AB - Fibronectin (FN) is a multifunctional extracellular matrix protein that plays an important role in cell proliferation, adhesion, and migration. FN expression or its role in colitis is not known. The goal of this study is to characterize FN expression, regulation, and role during intestinal inflammation. Wild-type and transgenic mice expressing luciferase under the control of the human FN promoter, given water or 3% dextran sodium sulfate, were used as animal models of colitis. The Caco2-BBE model intestinal epithelial cell line was used for in vitro studies. FN protein is abundantly expressed by surface epithelial cells in the normal colon. Immunohistochemistry and luciferase assay in mice expressing the FN promoter linked to luciferase demonstrated that FN synthesis was up-regulated during colitis, during both the acute phase and the healing phase. In vitro experiments demonstrated that FN increased the expression of the FN integrin receptor alpha5beta1 in a dose- and time-dependent manner. FN also induced the expression and activation of NF-kappaB. Further, FN potentiated Caco2-BBE cell attachment and wound healing, which was inhibited by RGD peptide as well as NF kappaB inhibitors MG-132 and 1-pyrrolidinecarbodithioic acid, ammonium salt. In conclusion, FN is abundantly expressed and synthesized by colonic epithelial cells. FN is transcriptionally up-regulated in epithelial cells during both the dextran sodium sulfate-induced colitic and the recovery phase. FN enhances cell attachment and wound healing, which is dependent on binding to the integrin receptor and the NF-kappaB signaling. Together our data show that epithelial derived FN potentiates cell attachment and wound healing through epithelial matrix interactions and that FN expression may have important implications for maintaining normal epithelial integrity as well as regulating epithelial response to injury during colitis. PMID- 17855341 TI - Chemical genetics define the roles of p38alpha and p38beta in acute and chronic inflammation. AB - The p38 MAP kinase signal transduction pathway is an important regulator of proinflammatory cytokine production and inflammation. Defining the roles of the various p38 family members, specifically p38alpha and p38beta, in these processes has been difficult. Here we use a chemical genetics approach using knock-in mice in which either p38alpha or p38beta kinase has been rendered resistant to the effects of specific inhibitors along with p38beta knock-out mice to dissect the biological function of these specific kinase isoforms. Mice harboring a T106M mutation in p38alpha are resistant to pharmacological inhibition of LPS-induced TNF production and collagen antibody-induced arthritis, indicating that p38beta activity is not required for acute or chronic inflammatory responses. LPS-induced TNF production, however, is still completely sensitive to p38 inhibitors in mice with a T106M point mutation in p38beta. Similarly, p38beta knock-out mice respond normally to inflammatory stimuli. These results demonstrate conclusively that specific inhibition of the p38alpha isoform is necessary and sufficient for anti inflammatory efficacy in vivo. PMID- 17855342 TI - Oligomerization and transglutaminase cross-linking of the cystatin CRES in the mouse epididymal lumen: potential mechanism of extracellular quality control. AB - CRES (cystatin-related epididymal spermatogenic), a member of the cystatin superfamily of cysteine protease inhibitors, is expressed in the epididymis and spermatozoa, suggesting specialized roles in reproduction. Several cystatin family members oligomerize, including cystatin C that forms amyloid deposits associated with cerebral amyloid angiopathy. Our studies demonstrate that CRES also forms oligomers. Size exclusion chromatography revealed the presence of multiple forms of CRES in the epididymal luminal fluid, including SDS-sensitive and SDS-resistant high molecular mass complexes. In vitro experiments demonstrated that CRES is a substrate for transglutaminase and that an endogenous transglutaminase activity in the epididymal lumen catalyzed the formation of SDS resistant CRES complexes. The use of a conformation-dependent antibody that recognizes only the oligomeric precursors to amyloid, negative stain electron microscopy, and Congo Red staining showed that CRES adopted similar oligomeric and fibrillar structures during its aggregation as other amyloidogenic proteins, suggesting that CRES has the potential to form amyloid in the epididymal lumen. The addition of transglutaminase, however, prevented the formation of CRES oligomers recognized by the conformation antibody by cross-linking CRES into an amorphous structure. We propose that transglutaminase activity in the epididymal lumen may function as a mechanism of extracellular quality control by diverting proteins such as CRES from the amyloidogenic pathway. PMID- 17855343 TI - Soluble Abeta inhibits specific signal transduction cascades common to the insulin receptor pathway. AB - Numerous studies have now shown that the amyloid beta-protein (Abeta), the principal component of cerebral plaques in Alzheimer disease, rapidly and potently inhibits certain forms of synaptic plasticity. The amyloid (or Abeta) hypothesis proposes that the continuous disruption of normal synaptic physiology by Abeta contributes to the development of Alzheimer disease. However, there is little consensus about how Abeta mediates this inhibition at the molecular level. Using mouse primary hippocampal neurons, we observed that a brief treatment with cell-derived, soluble, human Abeta disrupted the activation of three kinases (Erk/MAPK, CaMKII, and the phosphatidylinositol 3-kinase-activated protein Akt/protein kinase B) that are required for long term potentiation, whereas two other kinases (protein kinase A and protein kinase C) were stimulated normally. An antagonist of the insulin receptor family of tyrosine kinases was found to mimic the pattern of Abeta-mediated kinase inhibition. We then found that soluble Abeta binds to the insulin receptor and interferes with its insulin-induced autophosphorylation. Taken together, these data demonstrate that physiologically relevant levels of naturally secreted Abeta interfere with insulin receptor function in hippocampal neurons and prevent the rapid activation of specific kinases required for long term potentiation. PMID- 17855344 TI - Dynamic regulation, desensitization, and cross-talk in discrete subcellular microdomains during beta2-adrenoceptor and prostanoid receptor cAMP signaling. AB - Dynamic and localized actions of cAMP are central to the generation of discrete cellular events in response to a range of G(s)-coupled receptor agonists. In the present study we have employed a cyclic nucleotide-gated channel sensor to report acute changes in cAMP in the restricted cellular microdomains adjacent to two different G(s)-coupled receptor pathways, beta(2)-adrenoceptors and prostanoid receptors that are expressed endogenously in HEK293 cells. We probed by either selective small interference RNA-mediated knockdown or dominant negative overexpression the contribution of key signaling components in the rapid attenuation of the local cAMP signaling and subsequent desensitization of each of these G-protein-coupled receptor signaling pathways immediately following receptor activation. Direct measurements of cAMP changes just beneath the plasma membrane of single HEK293 cells reveal novel insights into key regulatory roles provided by protein kinase A-RII, beta-arrestin2, cAMP phosphodiesterase-4D3, and cAMP phosphodiesterase-4D5. We provide new evidence for distinct modes of cAMP down-regulation in these two G(s)-linked pathways and show that these distinct G protein-coupled receptor signaling systems are subject to unidirectional, heterologous desensitization that allows for limited cross-talk between distinct, dynamically regulated pools of cAMP. PMID- 17855345 TI - A cysteine-rich protein from an arthropod stabilizes clotting mesh and immobilizes bacteria at injury sites. AB - Hemolymph coagulation in arthropods plays key roles in host defense, including sealing wounds to staunch bleeding and immobilizing invading microorganisms. We have previously reported that horseshoe crab transglutaminase (TGase) promotes cross-linking of a clotting protein (coagulin) with hemocyte-derived proteins (proxins), resulting in the formation of stable coagulin fibrils. Here we show that TGase also cross-links proxins to another hemocyte-derived protein named stablin. Stablin is a cysteine-rich protein of 131 residues. Surface plasmon resonance analysis revealed the specific interaction of stablin with proxin-1 at K(d) = 4.0 x 10(-9) m. Stablin was predominantly localized in the large granules of hemocytes and secreted by lipopolysaccharide-induced exocytosis. Interestingly, stablin bound to chitin at K(d) = 1.5 x 10(-8) m, as determined by using a quartz-crystal microbalance. Stablin also interacted with lipopolysaccharides and lipoteichoic acids and exhibited bacterial agglutinating activity against Gram-positive and -negative bacteria. Immunostaining showed that stablin is co-localized with coagulin in the clotting fibrils that effectively trap bacteria. Moreover, an anti-stablin antibody strongly inhibited the proper formation of the clotting fibrils. These data suggest that stablin promotes the formation of the clotting mesh and the immobilization of invading microbes at injury sites. In arthropods, the TGase-mediated cross-linking may play an important role in the initial stage of host defense, wound closure, and healing, as in the case of mammals. PMID- 17855346 TI - Oxidation of 2-Cys-peroxiredoxins by arachidonic acid peroxide metabolites of lipoxygenases and cyclooxygenase-2. AB - Human peroxiredoxins serve dual roles as anti-oxidants and regulators of H(2)O(2) mediated cell signaling. The functional versatility of peroxiredoxins depends on progressive oxidation of key cysteine residues. The sulfinic or sulfonic forms of peroxiredoxin lose their peroxidase activity, which allows cells to accumulate H(2)O(2) for signaling or pathogenesis in inflammation, cancer, and other disorders. We report that arachidonic acid lipid hydroperoxide metabolites of 5-, 12-, 15-lipoxygenase-1, and cyclooxygenase-2 oxidize the 2-Cys-peroxiredoxins 1, 2, and 3 to their sulfinic and sulfonic forms. When added exogenously to cells, 5 , 12- and 15-hydroperoxy-eicosatetraenoic acids also over-oxidized peroxiredoxins. Our results suggest that lipoxygenases and cyclooxygenases may affect 2-Cys peroxiredoxin signaling, analogous to NADPH oxidases in the "floodgate" model (Wood, Z. A., Poole, L. B, and Karplus P. A. (2003) Science 300, 600-653). Peroxiredoxin-dependent mechanisms may modulate the receptor dependent actions of autocoids derived from cellular lipoxygenase and cyclooxygenase catalysis. PMID- 17855347 TI - Developmental pluripotency-associated 4 (DPPA4) localized in active chromatin inhibits mouse embryonic stem cell differentiation into a primitive ectoderm lineage. AB - Because embryonic stem (ES) cells can proliferate indefinitely in an undifferentiated state and differentiate into various cell types, ES cells are expected to be useful for cell replacement therapy and basic research on early embryogenesis. Although molecular mechanisms of ES cell self-renewal have been studied, many uncharacterized genes expressed in ES cells remain to be clarified. Developmental pluripotency associated 4 (Dppa4) is one such gene highly expressed in both ES cells and early embryos. Here, we investigated the role of Dppa4 in mouse ES cell self-renewal and differentiation. We generated Dppa4-overexpressing ES cells under the control of tetracycline. Dppa4 overexpression suppressed cell proliferation and formation of embryoid bodies and caused massive cell death in differentiating ES cells. Quantitative reverse transcription-PCR analysis showed that Dppa4 overexpression does not support ES cell self-renewal but partially inhibits ES cell differentiation. Suppression of Dppa4 expression by short hairpin RNA induced ES cell differentiation into a primitive ectoderm lineage. DPPA4 protein was localized in the ES cell nucleus associated with chromatin. Micrococcal nuclease digestion analysis and immunocytochemistry revealed that DPPA4 is associated with transcriptionally active chromatin. These findings indicate that DPPA4 is a nuclear factor associated with active chromatin and that it regulates differentiation of ES cells into a primitive ectoderm lineage. PMID- 17855348 TI - Activation of a dimeric metabotropic glutamate receptor by intersubunit rearrangement. AB - Although many G protein-coupled receptors (GPCRs) can form dimers, a possible role of this phenomenon in their activation remains elusive. A recent and exciting proposal is that a dynamic intersubunit interplay may contribute to GPCR activation. Here, we examined this possibility using dimeric metabotropic glutamate receptors (mGluRs). We first developed a system to perfectly control their subunit composition and show that mGluR dimers do not form larger oligomers. We then examined an mGluR dimer containing one subunit in which the extracellular agonist-binding domain was uncoupled from the G protein-activating transmembrane domain. Despite this uncoupling in one protomer, agonist stimulation resulted in symmetric activation of either transmembrane domain in the dimer with the same efficiency. This, plus other data, can only be explained by an intersubunit rearrangement as the activation mechanism. Although well established for other types of receptors such as tyrosine kinase and guanylate cyclase receptors, this is the first clear demonstration that such a mechanism may also apply to GPCRs. PMID- 17855349 TI - Epinephrine regulation of the endothelial nitric-oxide synthase: roles of RAC1 and beta3-adrenergic receptors in endothelial NO signaling. AB - beta-Adrenergic receptors (betaAR) play an important role in vasodilation, but the mechanisms whereby adrenergic pathways regulate the endothelial isoform of nitric-oxide synthase (eNOS) are incompletely understood. We found that epinephrine significantly increases eNOS activity in cultured bovine aortic endothelial cells (BAEC). Epinephrine-dependent eNOS activation was accompanied by an increase in phosphorylation of eNOS at Ser(1179) and with decreased eNOS phosphorylation at the inhibitory phosphoresidues Ser(116) and Thr(497). Epinephrine promoted activation of the small G protein Rac1 and also led to the activation of protein kinase A. All of these responses to epinephrine in BAEC were blocked by the beta(3)AR blocker SR59230A. We transfected and validated duplex small interfering RNA (siRNA) constructs to selectively "knock down" specific signaling proteins in BAEC. siRNA-mediated knockdown of Rac1 completely blocked all beta(3)AR signaling to eNOS and also abrogated epinephrine-dependent cAMP-dependent protein kinase (PKA) and Akt activation. However, siRNA-mediated knockdown of PKA did not affect Rac1 activation by epinephrine but did attenuate Akt activation by epinephrine. These findings indicate that Rac1 is an upstream regulator of beta(3)AR signaling to PKA and to eNOS and identify a novel beta(3)AR --> Rac1 --> PKA --> Akt pathway in endothelium. We exploited the p21 activated kinase pulldown assay to identify proteins associated with activated Rac1 and found that epinephrine stimulated the association of eNOS with Rac1; epinephrine-stimulated eNOS-Rac1 interactions were blocked by the beta(3)AR antagonist SR59230A. Co-transfection of eNOS cDNA with constitutively active Rac1 enhanced beta(3)AR-promoted eNOS-Rac1 association; co-transfection of eNOS with dominant negative Rac1 completely blocked the eNOS-Rac1 association. We also found that epinephrine-induced Rac1 --> PKA --> Akt pathway mediates beta(3)AR mediated endothelial cell migration. Taken together, our data establish that the small G protein Rac1 is a key regulator of beta(3)AR signaling in cultured aortic endothelial cells with potentially important implications for the pathways involved in adrenergic modulation of eNOS pathways in the vascular wall. PMID- 17855350 TI - Plexin-B1 utilizes RhoA and Rho kinase to promote the integrin-dependent activation of Akt and ERK and endothelial cell motility. AB - The semaphorins are a family of proteins originally identified as axon-guiding molecules in the developing nervous system that have been recently shown to regulate many cellular functions, including motility, in a variety of cell types. We have previously shown that in endothelial cells Semaphorin 4D acts through its receptor, Plexin-B1, to elicit a pro-angiogenic phenotype that involves the activation of the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway. Here we show through the use of a receptor chimeric approach, Plexin-B1 mutants, and dominant negative and pharmacological inhibitors that this response is dependent upon the activation of RhoA and its downstream target, Rho kinase (ROK). Indeed, we demonstrate that in endothelial cells, Semaphorin 4D promotes the formation of focal adhesion complexes, stress fibers, and the phosphorylation of myosin light chain, a response that was abolished by the use of ROK inhibitors and absent from cells expressing Plexin-B1 mutant constructs incapable of signaling to RhoA. Stress fiber polymerization and contraction are in turn necessary for RhoA-dependent pro-angiogenic signaling through Plexin-B1. Furthermore, we observed that in endothelial cells Plexin-B1 promotes the integrin-mediated activation of Pyk2, resulting in the stimulation of PI3K, Akt, and ERK. These findings provide evidence that Plexin-B1 promotes endothelial cell motility through RhoA and ROK by regulating the integrin-dependent signaling networks that result in the activation of PI3K and Akt. PMID- 17855351 TI - Glycogen synthase kinase-3alpha reduces cardiac growth and pressure overload induced cardiac hypertrophy by inhibition of extracellular signal-regulated kinases. AB - Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase having multiple functions and consisting of two isoforms, GSK-3alpha and GSK-3beta. Pressure overload increases expression of GSK-3alpha but not GSK-3beta. Despite our wealth of knowledge about GSK-3beta, the function of GSK-3alpha in the heart is not well understood. To address this issue, we made cardiac-specific GSK-3alpha transgenic mice (Tg). Left ventricular weight and cardiac myocyte size were significantly smaller in Tg than in non-Tg (NTg) mice, indicating that GSK-3alpha inhibits cardiac growth. After 4 weeks of aortic banding (transverse aortic constriction (TAC)), increases in left ventricular weight and myocyte size were significantly smaller in Tg than in NTg, indicating that GSK-3alpha inhibits cardiac hypertrophy. More severe cardiac dysfunction developed in Tg after TAC. Increases in fibrosis and apoptosis were greater in Tg than in NTg after TAC. Among signaling molecules screened, ERK phosphorylation was decreased in Tg. Adenovirus mediated overexpression of GSK-3alpha, but not GSK-3beta, inhibited ERK in cultured cardiac myocytes. Knockdown of GSK-3alpha increased ERK phosphorylation, an effect that was inhibited by PD98059, rottlerin, and protein kinase Cepsilon (PKCepsilon) inhibitor peptide, suggesting that GSK-3alpha inhibits ERK through PKC-MEK-dependent mechanisms. Knockdown of GSK-3alpha increased protein content and reduced apoptosis, effects that were abolished by PD98059, indicating that inhibition of ERK plays a major role in the modulation of cardiac growth and apoptosis by GSK-3alpha. In conclusion, up-regulation of GSK-3alpha inhibits cardiac growth and pressure overload-induced cardiac hypertrophy but increases fibrosis and apoptosis in the heart. The anti-hypertrophic and pro-apoptotic effect of GSK-3alpha is mediated through inhibition of ERK. PMID- 17855352 TI - Dynamic interaction between Src and C-terminal Src kinase in integrin alphaIIbbeta3-mediated signaling to the cytoskeleton. AB - Integrin-bound Src tyrosine kinase mediates alpha(IIb)beta(3) out-side-in signaling to the cytoskeleton required for platelet adhesion and thrombus formation. Src activation (signal initiation) by phosphorylation of Tyr-418 occurs at lamellipodia leading edges. However, little is known about Src inactivation mediated by C-terminal Src kinase (Csk) Tyr-529 phosphorylation. In an established platelet model cell line (A5-Chinese hamster ovary), we studied the inactivation of Src during alpha(IIb)beta(3)-mediated adhesion to fibrinogen with live cell fluorescence resonance energy transfer (FRET) microscopy. Imaging revealed highly dynamic Src-Csk interactions at the leading edges of active lamellipodia. The Src-Csk interaction followed a highly dynamic pattern. Every 2 3 min, Src-Csk complexes moved inward in the cell, reorganized, and formed stable focal adhesions. These accumulations were primarily seen during retraction of lamellipodia, whereas no interaction was observed during protrusions. Western blot analysis during the run time of FRET signaling revealed an increase in Csk mediated SrcTyr-529 phosphorylation with a parallel decline of tyrosine 418 phosphorylation. Mutation analysis provided additional insights into the role of Src. Although inactivation of Csk (CskK222R) had no effect on cell adhesion and spreading efficiency, cells with constitutively active expressed Src (SrcY529F) exhibited hardly any adhesion and no spreading. The few adherent cells showed weak focal adhesions that were disorganized and oversized. The data clearly demonstrate the important role of tight Src control by Csk for functional cell adhesion and spreading. The novel experimental FRET approach reported here for the inactivation of Src can be readily applied to other integrin and signaling pathways, including closely related Src family kinase members. PMID- 17855353 TI - Anticancer drugs up-regulate HspBP1 and thereby antagonize the prosurvival function of Hsp70 in tumor cells. AB - The 70-kDa heat shock protein (Hsp70) is up-regulated in a wide variety of tumor cell types and contributes to the resistance of these cells to the induction of cell death by anticancer drugs. Hsp70 binding protein 1 (HspBP1) modulates the activity of Hsp70 but its biological significance has remained unclear. We have now examined whether HspBP1 might interfere with the prosurvival function of Hsp70, which is mediated, at least in part, by inhibition of the death-associated permeabilization of lysosomal membranes. HspBP1 was found to be expressed at a higher level than Hsp70 in all normal and tumor cell types examined. Tumor cells with a high HspBP1/Hsp70 molar ratio were more susceptible to anticancer drugs than were those with a low ratio. Ectopic expression of HspBP1 enhanced this effect of anticancer drugs in a manner that was both dependent on the ability of HspBP1 to bind to Hsp70 and sensitive to the induction of Hsp70 by mild heat shock. Furthermore, anticancer drugs up-regulated HspBP1 expression, whereas prevention of such up-regulation by RNA interference reduced the susceptibility of tumor cells to anticancer drugs. Overexpression of HspBP1 promoted the permeabilization of lysosomal membranes, the release of cathepsins from lysosomes into the cytosol, and the activation of caspase-3 induced by anticancer drugs. These results suggest that HspBP1, by antagonizing the prosurvival activity of Hsp70, sensitizes tumor cells to cathepsin-mediated cell death. PMID- 17855354 TI - Epithelial sodium channel exit from the endoplasmic reticulum is regulated by a signal within the carboxyl cytoplasmic domain of the alpha subunit. AB - Epithelial sodium channels (ENaCs) are assembled in the endoplasmic reticulum (ER) from alpha, beta, and gamma subunits, each with two transmembrane domains, a large extracellular loop, and cytoplasmic amino and carboxyl termini. ENaC maturation involves transit through the Golgi complex where Asn-linked glycans are processed to complex type and the channel is activated by furin-dependent cleavage of the alpha and gamma subunits. To identify signals in ENaC for ER retention/retrieval or ER exit/release, chimera were prepared with the interleukin alpha subunit (Tac) and each of the three cytoplasmic carboxyl termini of mouse ENaC (Tac-Ct) or with gamma-glutamyltranspeptidase and each of the three cytoplasmic amino termini (Nt-GGT). By monitoring acquisition of endoglycosidase H resistance after metabolic labeling, we found no evidence of ER retention of any chimera when compared with control Tac or GGT, but we did observe enhanced exit of Tac-alphaCt when compared with Tac. ER exit of ENaC was assayed after metabolic labeling by following the appearance of cleaved alpha as cleaved alpha subunit, but not non-cleaved alpha, is endoglycosidase H-resistant. Interestingly ER exit of epitope-tagged and truncated alpha (alphaDelta624-699 V5) with full-length betagamma was similar to wild type alpha (+betagamma), whereas ER exit of ENaC lacking the entire cytoplasmic carboxyl tail of alpha (alphaDelta613-699-V5 +betagamma) was significantly reduced. Subsequent analysis of ER exit for ENaCs with mutations within the intervening sequence (613)HRFRSRYWSPG(623) within the context of the full-length alpha revealed that mutation alphaRSRYW(620) to AAAAA significantly reduced ER exit. These data indicate that ER exit of ENaC is regulated by a signal within the alpha subunit carboxyl cytoplasmic tail. PMID- 17855355 TI - CMO1 deficiency abolishes vitamin A production from beta-carotene and alters lipid metabolism in mice. AB - Carotenoids are currently investigated regarding their potential to lower the risk of chronic disease and to combat vitamin A deficiency in humans. These plant derived compounds must be cleaved and metabolically converted by intrinsic carotenoid oxygenases to support the panoply of vitamin A-dependent physiological processes. Two different carotenoid-cleaving enzymes were identified in mammals, the classical carotenoid-15,15'-oxygenase (CMO1) and a putative carotenoid-9',10' oxygenase (CMO2). To analyze the role of CMO1 in mammalian physiology, here we disrupted the corresponding gene by targeted homologous recombination in mice. On a diet providing beta-carotene as major vitamin A precursor, vitamin A levels fell dramatically in several tissues examined. Instead, this mouse mutant accumulated the provitamin in large quantities (e.g. as seen by an orange coloring of adipose tissues). Besides impairments in beta-carotene metabolism, CMO1 deficiency more generally interfered with lipid homeostasis. Even on a vitamin A-sufficient chow, CMO1(-/-) mice developed a fatty liver and displayed altered serum lipid levels with elevated serum unesterified fatty acids. Additionally, this mouse mutant was more susceptible to high fat diet-induced impairments in fatty acid metabolism. Quantitative reverse transcription-PCR analysis revealed that the expression of peroxisome proliferator-activated receptor gamma-regulated marker genes related to adipogenesis was elevated in visceral adipose tissues. Thus, our study identifies CMO1 as the key enzyme for vitamin A production and provides evidence for a role of carotenoids as more general regulators of lipid metabolism. PMID- 17855356 TI - Quail Sulf1 function requires asparagine-linked glycosylation. AB - The heparan sulfate endosulfatases Sulf1 and Sulf2 are cell-surface enzymes that control growth factor signaling through regulation of the 6-O-sulfation states of cell-surface and matrix heparan sulfate proteoglycans. Here, we report that quail Sulf1 (QSulf1) is an asparagine-linked glycosylated protein. Domain mapping studies in combination with a protein glycosylation prediction program identified multiple asparagine-linked glycosylation sites in the enzymatic and C-terminal domains. Glycosylation inhibitor studies revealed that glycosylation of QSulf1 is essential for its enzymatic activity, membrane targeting, and secretion. Furthermore, N-glycanase cleavage of asparagine-linked sites in native QSulf1 provided direct evidence that these N-linked glycosylation sites are specifically required for QSulf1 heparin binding and its 6-O-desulfation activity, revealing that N-linked glycosylation has a key role in the control of sulfatase enzymatic function. PMID- 17855357 TI - Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase. AB - We have studied the mechanism of A-769662, a new activator of AMP-activated protein kinase (AMPK). Unlike other pharmacological activators, it directly activates native rat AMPK by mimicking both effects of AMP, i.e. allosteric activation and inhibition of dephosphorylation. We found that it has no effect on the isolated alpha subunit kinase domain, with or without the associated autoinhibitory domain, or on interaction of glycogen with the beta subunit glycogen-binding domain. Although it mimics actions of AMP, it has no effect on binding of AMP to the isolated Bateman domains of the gamma subunit. The addition of A-769662 to mouse embryonic fibroblasts or primary mouse hepatocytes stimulates phosphorylation of acetyl-CoA carboxylase (ACC), effects that are completely abolished in AMPK-alpha1(-/-)alpha2(-/-) cells but not in TAK1(-/-) mouse embryonic fibroblasts. Phosphorylation of AMPK and ACC in response to A 769662 is also abolished in isolated mouse skeletal muscle lacking LKB1, a major upstream kinase for AMPK in this tissue. However, in HeLa cells, which lack LKB1 but express the alternate upstream kinase calmodulin-dependent protein kinase kinase-beta, phosphorylation of AMPK and ACC in response to A-769662 still occurs. These results show that in intact cells, the effects of A-769662 are independent of the upstream kinase utilized. We propose that this direct and specific AMPK activator will be a valuable experimental tool to understand the physiological roles of AMPK. PMID- 17855358 TI - Structural and functional characterization of the interaction between cyclophilin B and a heparin-derived oligosaccharide. AB - The chemotaxis and integrin-mediated adhesion of T lymphocytes triggered by secreted cyclophilin B (CypB) depend on interactions with both cell surface heparan sulfate proteoglycans (HSPG) and the extracellular domain of the CD147 membrane receptor. Here, we use NMR spectroscopy to characterize the interaction of CypB with heparin-derived oligosaccharides. Chemical shift perturbation experiments allowed the precise definition of the heparan sulfate (HS) binding site of CypB. The N-terminal extremity of CypB, which contains a consensus sequence for heparin-binding proteins was modeled on the basis of our experimental NMR data. Because the HS binding site extends toward the CypB catalytic pocket, we measured its peptidyl-prolyl cis-trans isomerase (PPIase) activity in the absence or presence of a HS oligosaccharide toward a CD147 derived peptide. We report the first direct evidence that CypB is enzymatically active on CD147, as it is able to accelerate the cis/trans isomerization of the Asp(179)-Pro(180) bond in a CD147-derived peptide. However, HS binding has no significant influence on this PPIase activity. We thus conclude that the glycanic moiety of HSPG serves as anchor for CypB at the cell surface, and that the signal could be transduced by CypB via its PPIase activity toward CD147. PMID- 17855359 TI - Conditional intestinal lipotoxicity in Apobec-1-/- Mttp-IKO mice: a survival advantage for mammalian intestinal apolipoprotein B mRNA editing. AB - Mammalian small intestinal lipid absorption requires the coordinated interactions of apolipoprotein B (apoB) and the microsomal triglyceride transfer protein (Mttp). The observation that apoB100 displays greater dependence on Mttp availability than does apoB48 prompted us to examine the phenotype of Mttp deletion in an Apobec-1(-/-) background (i.e. apoB100 Mttp-IKO). 20% apoB100 Mttp IKO mice died on a chow diet, and >90% died following high fat feeding (versus 0 and 11% apoB48 Mttp-IKO mice, respectively). Intestinal adaptation occurred in apoB48 Mttp-IKO mice in response to high fat feeding, evidenced by increased bromodeoxyuridine incorporation and villus lengthening, changes that did not occur in apoB100 Mttp-IKO mice. There was an exaggerated unfolded protein response (UPR), which became more pronounced in apoB100 Mttp-IKO mice. To examine the role of endoplasmic reticulum stress and the UPR in the lipotoxic effects of Mttp deletion, we administered tauroursodeoxycholate to apoB100 Mttp-IKO mice upon initiation of high fat feeding. Tauroursodeoxycholate administration abrogated the UPR but produced an unexpected acceleration in the onset of lethality in apoB100 Mttp-IKO mice. The findings demonstrate that there is activation of the UPR with lethal lipotoxicity in conditional intestinal apoB100 Mttp-IKO mice. Together the data provide the first plausible biological evidence for a survival advantage for mammalian intestinal apoB mRNA editing. PMID- 17855360 TI - SorLA/LR11 regulates processing of amyloid precursor protein via interaction with adaptors GGA and PACS-1. AB - SorLA has been recognized as a novel sorting receptor that regulates trafficking and processing of the amyloid precursor protein (APP) and that represents a significant risk factor for sporadic Alzheimer disease. Here, we investigated the cellular mechanisms that control intracellular trafficking of sorLA and their relevance for APP processing. We demonstrate that sorLA acts as a retention factor for APP in trans-Golgi compartments/trans-Golgi network, preventing release of the precursor into regular processing pathways. Proper localization and activity of sorLA are dependent on functional interaction with GGA and PACS 1, adaptor proteins involved in protein transport to and from the trans-Golgi network. Aberrant targeting of sorLA to the recycling compartment or the plasma membrane causes faulty APP trafficking and imbalance in non-amyloidogenic and amyloidogenic processing fates. Thus, our findings identified altered routing of sorLA as a major cellular mechanism contributing to abnormal APP processing and enhanced amyloid beta-peptide formation. PMID- 17855361 TI - Stat3 isoforms, alpha and beta, demonstrate distinct intracellular dynamics with prolonged nuclear retention of Stat3beta mapping to its unique C-terminal end. AB - Two isoforms of Stat3 (signal transducer and activator of transcription 3) are expressed in cells, alpha (p92) and beta (p83), both derived from a single gene by alternative mRNA splicing. The 55-residue C-terminal transactivation domain of Stat3alpha is deleted in Stat3beta and replaced by seven unique C-terminal residues (CT7) whose function remains uncertain. We subcloned the open reading frames of Stat3alpha and Stat3beta into the C terminus of green fluorescent protein (GFP). Fluorescent microscopic analysis of HEK293T cells transiently transfected with GFP-Stat3alpha or GFP-Stat3beta revealed similar kinetics and cytokine concentration dependence of nuclear accumulation; these findings were confirmed by high throughput microscope analysis of murine embryonic fibroblasts that lacked endogenous Stat3 but stably expressed either GFP-Stat3alpha or GFP Stat3beta. However, although time to half-maximal cytoplasmic reaccumulation after cytokine withdrawal was 15 min for GFP-Stat3alpha, it was >180 min for GFP Stat3beta. Furthermore, although the intranuclear mobility of GFP-Stat3alpha was rapid and increased with cytokine stimulation, the intranuclear mobility of GFP Stat3beta in unstimulated cells was slower than that of GFP-Stat3alpha in unstimulated cells and was slowed further following cytokine stimulation. Deletion of the unique CT7 domain from Stat3beta eliminated prolonged nuclear retention but did not alter its intranuclear mobility. Thus, Stat3alpha and Stat3beta have distinct intracellular dynamics, with Stat3beta exhibiting prolonged nuclear retention and reduced intranuclear mobility especially following ligand stimulation. Prolonged nuclear retention, but not reduced intranuclear mobility, mapped to the CT7 domain of Stat3beta. PMID- 17855362 TI - APOBEC3G inhibits DNA strand transfer during HIV-1 reverse transcription. AB - Human APOBEC3G (hA3G) has been identified as an anti-HIV-1 host factor. The presence of hA3G in HIV-1 strongly inhibits the ability of the virus to produce new viral DNA upon infection. In this report, we demonstrate that the reduction of late viral DNA synthesis is due to the inhibition by hA3G of the strand transfer steps that occur during reverse transcription. Analysis of viral cDNA intermediates in vivo reveals that hA3G causes an inhibition of the minus and plus strand transfers, without having a significant impact on DNA elongation. Using an in vitro system to measure minus strand transfer similarly shows a dose dependent reduction of strand transfer by hA3G. This inhibition of strand transfer occurs independently the editing activity of hA3G and is correlated with its ability to prevent RNaseH degradation of the template RNA. PMID- 17855363 TI - A yeast model of the neurogenic ataxia retinitis pigmentosa (NARP) T8993G mutation in the mitochondrial ATP synthase-6 gene. AB - NARP (neuropathy, ataxia, and retinitis pigmentosa) and MILS (maternally inherited Leigh syndrome) are mitochondrial disorders associated with point mutations of the mitochondrial DNA (mtDNA) in the gene encoding the Atp6p subunit of the ATP synthase. The most common and studied of these mutations is T8993G converting the highly conserved leucine 156 into arginine. We have introduced this mutation at the corresponding position (183) of yeast Saccharomyces cerevisiae mitochondrially encoded Atp6p. The "yeast NARP mutant" grew very slowly on respiratory substrates, possibly because mitochondrial ATP synthesis was only 10% of the wild type level. The mutated ATP synthase was found to be correctly assembled and present at nearly normal levels (80% of the wild type). Contrary to what has been reported for human NARP cells, the reverse functioning of the ATP synthase, i.e. ATP hydrolysis in the F(1) coupled to F(0)-mediated proton translocation out of the mitochondrial matrix, was significantly compromised in the yeast NARP mutant. Interestingly, the oxygen consumption rate in the yeast NARP mutant was decreased by about 80% compared with the wild type, due to a selective lowering in cytochrome c oxidase (complex IV) content. This finding suggests a possible regulatory mechanism between ATP synthase activity and complex IV expression in yeast mitochondria. The availability of a yeast NARP model could ease the search for rescuing mechanisms against this mitochondrial disease. PMID- 17855364 TI - Temperature-dependent modulation of CaV3 T-type calcium channels by protein kinases C and A in mammalian cells. AB - Modulation of low voltage-activated Ca(V)3 T-type calcium channels remains poorly characterized compared with high voltage-activated Ca(V)1 and Ca(V)2 calcium channels. Notably, it is yet unresolved whether Ca(V)3 channels are modulated by protein kinases in mammalian cells. In this study, we demonstrate that protein kinase A (PKA) and PKC (but not PKG) activation induces a potent increase in Ca(V)3.1, Ca(V)3.2, and Ca(V)3.3 currents in various mammalian cell lines. Notably, we show that protein kinase effects occur at physiological temperature ( approximately 30-37 degrees C) but not at room temperature ( approximately 22-27 degrees C). This temperature dependence could involve kinase translocation, which is impaired at room temperature. A similar temperature dependence was observed for PKC-mediated increase in high voltage-activated Ca(V)2.3 currents. We also report that neither Ca(V)3 surface expression nor T-current macroscopic properties are modified upon kinase activation. In addition, we provide evidence for the direct phosphorylation of Ca(V)3.2 channels by PKA in in vitro assays. Overall, our results clearly establish the role of PKA and PKC in the modulation of Ca(V)3 T-channels and further highlight the key role of the physiological temperature in the effects described. PMID- 17855365 TI - FSCB, a novel protein kinase A-phosphorylated calcium-binding protein, is a CABYR binding partner involved in late steps of fibrous sheath biogenesis. AB - We report characterization of a novel testis- and sperm-specific protein, FSCB (fibrous sheath CABYR binding), that is expressed post-meiotically and localized in mouse sperm flagella. FSCB was identified as a binding partner of CABYR, a calcium-binding protein that is tyrosine-phosphorylated during capacitation. Orthologous genes of FSCB are present in other mammals, including rat and human, and conserved motifs in FSCB include PXXP, proline-rich and extensin-like regions. FSCB is phosphorylated by protein kinase A as shown by in vitro phosphorylation assay and also by determining phosphorylation sites in native FSCB from mouse sperm. Calcium overlay assay showed that FSCB is a calcium binding protein from sperm. FSCB is a post meiotic protein first expressed at step 11 of mouse spermatogenesis in the elongating spermatids, and it subsequently incorporates into the flagellar principal piece of the sperm. Ultrastructurally, FSCB localized to a cortical layer of intermediate electron density at the surface of the ribs and longitudinal columns of the fibrous sheath. Due to its temporal appearance during spermiogenesis and location at the cortex of the fibrous sheath, FSCB is postulated to be involved in the later stages of fibrous sheath assembly. PMID- 17855366 TI - Structural basis of glyphosate tolerance resulting from mutations of Pro101 in Escherichia coli 5-enolpyruvylshikimate-3-phosphate synthase. AB - Glyphosate, the world's most used herbicide, is a massive success because it enables efficient weed control with minimal animal and environmental toxicity. The molecular target of glyphosate is 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), which catalyzes the sixth step of the shikimate pathway in plants and microorganisms. Glyphosate-tolerant variants of EPSPS constitute the basis of genetically engineered herbicide-tolerant crops. A single-site mutation of Pro(101) in EPSPS (numbering according to the enzyme from Escherichia coli) has been implicated in glyphosate-resistant weeds, but this residue is not directly involved in glyphosate binding, and the basis for this phenomenon has remained unclear in the absence of further kinetic and structural characterization. To probe the effects of mutations at this site, E. coli EPSPS enzymes were produced with glycine, alanine, serine, or leucine substituted for Pro(101). These mutant enzymes were analyzed by steady-state kinetics, and the crystal structures of the substrate binary and substrate.glyphosate ternary complexes of P101S and P101L EPSPS were determined to between 1.5- and 1.6-A resolution. It appears that residues smaller than leucine may be substituted for Pro(101) without decreasing catalytic efficiency. Any mutation at this site results in a structural change in the glyphosate-binding site, shifting Thr(97) and Gly(96) toward the inhibitor molecule. We conclude that the decreased inhibitory potency observed for glyphosate is a result of these mutation-induced long-range structural changes. The implications of our findings concerning the development and spread of glyphosate-resistant weeds are discussed. PMID- 17855367 TI - Platelet-derived growth factor-induced stabilization of cyclooxygenase 2 mRNA in rat smooth muscle cells requires the c-Src family of protein-tyrosine kinases. AB - Cyclooxygenases (COXs) are crucial rate-limiting enzymes required for the biosynthesis of prostaglandins. COX-2 is an inducible isoform of this enzyme, which is believed to play important roles in the development of atherosclerotic vascular disease. We found that COX-2 expression rapidly increases in response to various signaling events, including activation of the platelet-derived growth factor (PDGF) pathway. Activation of PDGF receptor (PDGFR) in rat aortic vascular smooth muscle cells leads to c-Src-dependent stabilization of COX-2 mRNA requiring an AU-rich region within the 3'-untranslated region of this transcript. This regulation correlates with tyrosine phosphorylation of the RNA-associated protein, CUG-binding protein 2 (CUGBP2), which appears to enhance its interaction with COX-2 mRNA. Site-directed mutagenesis of putative tyrosine phosphorylation sites in CUGBP2 identified tyrosine 39 as a c-Src target, and a CUGBP2 with a mutated tyrosine 39 displayed an attenuated ability to bind COX-2 mRNA. We further show that silencing of CUGBP2 with specific small interference RNAs significantly reduces PDGF-dependent induction of COX-2 at both mRNA and protein levels. Furthermore, forced expression of CUGBP2 or constitutively active c-Src leads to stabilization of co-expressed COX-2 mRNA. Finally, in vitro RNA decay assay demonstrates that CUGBP2 is functionally required for the stabilization of COX-2 mRNA. Therefore, our data suggest that tyrosine phosphorylation of CUGBP2 is an important underlying mechanism for the ability of PDGFR/c-Src signaling to control the stability of COX-2 mRNA. PMID- 17855368 TI - Identification of a novel inhibitor of differentiation-1 (ID-1) binding partner, caveolin-1, and its role in epithelial-mesenchymal transition and resistance to apoptosis in prostate cancer cells. AB - Recently, ID-1 (inhibitor of differentiation/DNA binding) is suggested as an oncogene and is reported to promote cell proliferation, invasion, and survival in several types of human cancer cells through multiple signaling pathways. However, how Id-1 interacts with these pathways and the immediate downstream effectors of the Id-1 protein are not known. In this study, using a yeast two-hybrid screening technique, we identified a novel Id-1-interacting protein, caveolin-1 (Cav-1), a cell membrane protein, and a positive regulator of cell survival and metastasis in prostate cancer. Using an immunoprecipitation method, we found that the helix loop-helix domain of the Id-1 protein was essential for the physical interaction between Id-1 and Cav-1. In addition, we also demonstrated that the physical interaction between Id-1 and Cav-1 played a key role in the epithelial mesenchymal transition and increased cell migration rate as well as resistance to taxol-induced apoptosis in prostate cancer cells. Furthermore, our results revealed that this effect was regulated by Id-1-induced Akt activation through promoting the binding activity between Cav-1 and protein phosphatase 2A. Our study demonstrates a novel Id-1 binding partner and suggests a molecular mechanism that mediates the function of Id-1 in promoting prostate cancer progression through activation of the Akt pathway leading to cancer cell invasion and resistance to anticancer drug-induced apoptosis. PMID- 17855369 TI - SWI/SNF chromatin remodeling ATPase Brm regulates the differentiation of early retinal stem cells/progenitors by influencing Brn3b expression and Notch signaling. AB - Based on a variety of approaches, evidence suggests that different cell types in the vertebrate retina are generated by multipotential progenitors in response to interactions between cell intrinsic and cell extrinsic factors. The identity of some of the cellular determinants that mediate such interactions has emerged, shedding light on mechanisms underlying cell differentiation. For example, we know now that Notch signaling mediates the influence of the microenvironment on states of commitment of the progenitors by activating transcriptional repressors. Cell intrinsic factors such as the proneural basic helix-loop-helix and homeodomain transcription factors regulate a network of genes necessary for cell differentiation and maturation. What is missing from this picture is the role of developmental chromatin remodeling in coordinating the expression of disparate classes of genes for the differentiation of retinal progenitors. Here we describe the role of Brm, an ATPase in the SWI/SNF chromatin remodeling complex, in the differentiation of retinal progenitors into retinal ganglion cells. Using the perturbation of expression and function analyses, we demonstrate that Brm promotes retinal ganglion cell differentiation by facilitating the expression and function of a key regulator of retinal ganglion cells, Brn3b, and the inhibition of Notch signaling. In addition, we demonstrate that Brm promotes cell cycle exit during retinal ganglion cell differentiation. Together, our results suggest that Brm represents one of the nexus where diverse information of cell differentiation is integrated during cell differentiation. PMID- 17855370 TI - Fe65 stimulates proteolytic liberation of the beta-amyloid precursor protein intracellular domain. AB - The beta-amyloid precursor protein (APP)-binding protein Fe65 is involved in APP nuclear signaling and several steps in APP proteolytic processing. In this study, we show that Fe65 stimulates gamma-secretase-mediated liberation of the APP intracellular domain (AICD). The mechanism of Fe65-mediated stimulation of AICD formation appears to be through enhanced production of the carboxyl-terminal fragment substrates of gamma-secretase and direct stimulation of processing by gamma-secretase. The stimulatory capacity of Fe65 is isoform-dependent, as the non-neuronal and a2 isoforms promote APP processing more effectively than the exon 9 inclusive neuronal form of Fe65. Intriguingly, Fe65 stimulation of AICD production appears to be inversely related to pathogenic beta-amyloid production as the Fe65 isoforms profoundly stimulate AICD production and simultaneously decrease Abeta42 production. Despite the capacity of Fe65 to stimulate gamma secretase-mediated APP proteolysis, it does not rescue the loss of proteolytic function associated with the presenilin-1 familial Alzheimer disease mutations. These data suggest that Fe65 regulation of APP proteolysis may be integrally associated with its nuclear signaling function, as all antecedent proteolytic steps prior to release of Fe65 from the membrane are fostered by the APP-Fe65 interaction. PMID- 17855371 TI - The dodecin from Thermus thermophilus, a bifunctional cofactor storage protein. AB - Dodecins are so far the smallest known flavoproteins (68-71 amino acids) and are most likely involved in prokaryotic flavin storage. The dodecin monomers adopt a simple betaalphabetabeta-fold and assemble to hollow sphere-like dodecameric complexes. Flavin binding by the dodecin from Thermus thermophilus showed a 1:1 stoichiometry and apparent dissociation constants in the submicromolar to nanomolar range as characterized by isothermal titration calorimetry and fluorescence titrations. The x-ray structures of the flavin-prebound and FMN reconstituted state of the T. thermophilus dodecin revealed binding of FMN dimers in a novel si-si- rather than the re-re- orientation of their isoalloxazine moieties as found before in an archaeal dodecin. Electron paramagnetic resonance studies demonstrated that upon reduction the excess electron is localized only on one flavin, thus making dodecin-bound flavins highly refractory to redox chemistry. Besides FMN dimers, trimers of coenzyme A are additionally bound to this eubacterial dodecin along the 3-fold symmetry face II of the dodecin complex. Therefore, dodecins can act as bifunctional cofactor storage proteins that sequester catalytic cofactors in prokaryotes very efficiently in an aggregated and unreactive state. PMID- 17855372 TI - The PDZ domain-binding motif of the human T cell leukemia virus type 1 tax protein induces mislocalization of the tumor suppressor hScrib in T cells. AB - Interactions with cellular PDZ domain-containing proteins obviously contribute to the tumorigenic potential of several viral oncoproteins. In this regard, the oncogenic potential of the human T cell leukemia virus type 1 Tax protein correlates with its binding capacity to the tumor suppressor hDlg. Recent results show that hDlg in T cells is associated to a network of scaffolding proteins including another PDZ domain-containing protein termed hScrib. Interestingly, previous studies have revealed complementary activities of both proteins in the control of epithelial cell polarity. Here, we demonstrate that Tax can bind to hScrib and that the resulting Tax/hScrib complex is present in human T cell leukemia virus type 1-infected T cells. By confocal microscopy, we show that Tax modifies the localization of hScrib in transfected COS cells as well as in infected T cell lines and targets hScrib to particular spots exhibiting a granular distribution, mainly distributed in the cytoplasm. Given that Tax sequesters hScrib to these particular structures, we postulate that Tax might inhibit hScrib activity. Providing further support to this idea, we find that transient overexpression of hScrib attenuates T cell receptor-induced NFAT activity but that the presence of Tax counteracts this negative effect on the NFAT pathway. The fact that hDlg and hScrib are both targeted by Tax underlies their importance in T cell function. PMID- 17855373 TI - A new model to study compensatory mechanisms in MPTP-treated monkeys exhibiting recovery. AB - The cardinal symptoms in Parkinson's disease (PD), akinesia, rigidity and tremor, are only observed when the striatal level of dopamine is decreased by 60-80%. During the preclinical phase of PD, compensatory mechanisms are probably involved in delaying the appearance of motor symptoms. In a MPTP (1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine) monkey model of PD, a spontaneous recovery has been reported after initial intoxication suggesting that compensatory mechanisms are activated in this model as well. Assuming that mechanisms are similar in these phenomena, the study of recovery in monkeys following MPTP intoxication may enable identification of compensatory mechanisms involved in the preclinical phase of PD. In order to maximize the temporal similarity between PD and the MPTP model, we assessed a new progressive monkey model in which spontaneous recovery is expressed systematically and to characterize it based on (1) its behavioural features, and (2) the presence of compensatory mechanisms revealed by an immunohistological approach comparing dopaminergic and serotoninergic innervation between monkeys either exhibiting behavioural recovery or stable motor symptoms. This immunohistological study focused on the substantia nigra, striatum and pallidum, and their anatomical and functional subdivisions: sensorimotor, associative and limbic. The behavioural analysis revealed that with progressive MPTP intoxication motor symptoms were initially expressed in all monkeys. Observable recovery from these symptoms occurred in all monkeys (7/7) within 3-5 weeks after the last MPTP injection, and most exhibited a full recovery. In contrast, acute intoxication induced stable motor symptoms. Despite this obvious behavioural difference, immunohistological methods revealed that the loss of dopaminergic cell bodies in substantia nigra was substantial and similar in both MPTP-treated groups. However, quantification of fibres revealed that recovered monkeys displayed more dopaminergic and serotoninergic fibres than those with stable motor symptoms in sensorimotor and associative territories of striatum and more dopaminergic fibres in internal pallidum. This study provides a new model of PD where all monkeys expressed functional recovery from motor symptoms despite a large dopaminergic neuronal loss. The immunohistological results suggest that both dopamine and serotonin could be implicated in the compensatory mechanisms. PMID- 17855374 TI - Motor procedural learning in Parkinson's disease. AB - Functional neuroimaging research has repeatedly implicated the striatum in motor procedural learning, but attempts to explore this relation in patients with Parkinson's disease (PD) have yielded inconsistent results. Furthermore, the functional impact of procedural learning impairment is unknown. The present study sought to examine the effects of PD on procedural learning and to determine whether impaired procedural learning affects functional status. The performance of 95 non-demented PD patients on the serial reaction time task (SRTT) was compared with that of 44 demographically matched control subjects. The SRTT is a four-choice reaction time task in which visual stimuli are presented in six blocks of 100 trials either in a repeating sequence of 10 stimuli or randomly. Learning was inferred from the reduction of response times over five successive blocks of repeating sequence trials and from the increase in response times in the sixth random block. In addition, neuropsychological tests of declarative memory, executive and visuospatial functions were administered to all participants. Patients also received quantitative ratings of functional outcome. The two groups did not differ in the learning rate across blocks of repeating sequence trials. However, PD patients were significantly less efficient than controls in acquiring sequence-specific knowledge, although this impairment was relatively small (d = 0.38). Patients with more advanced clinical symptoms tended to show worse performance. Separate analyses of a subgroup of 24 non-medicated patients in the early stages of PD revealed no differences in SRTT performance relative to controls. Neuropsychological testing showed impairments in attention and executive functions, immediate and delayed explicit memory and visuospatial skills in the PD group, but none of the cognitive measures were related to procedural learning. Reduced motor sequence learning in PD patients did not influence their functional status. These findings indicate that procedural learning impairment is not an early feature of PD, but is likely to emerge with progression of the disease, independently of cognitive dysfunction or dopaminergic medication. PMID- 17855375 TI - Dorsolateral prefrontal cortex dysfunction in presymptomatic Huntington's disease: evidence from event-related fMRI. AB - Evidence from magnetic resonance imaging (MRI) suggests early structural and functional brain changes in individuals with the Huntington's disease (HD) gene mutation who are presymptomatic for the motor symptoms of the disorder (pre-HD subjects). The objective of this study was to investigate the functional neuroanatomy of verbal working memory (WM) in pre-HD subjects. By means of event related functional MRI, we studied healthy controls (n = 16) and pre-HD subjects (n = 16) with a parametric WM paradigm comprising three different WM load levels. Voxel-based morphometry (VBM) was used to control potentially confounding brain atrophy. Although WM performance did not significantly differ between pre-HD subjects and healthy controls, pre-HD subjects showed a significantly decreased activation of the left dorsolateral prefrontal cortex (DLPFC) at intermediate and high WM load levels only. This region was not affected by early cortical atrophy, as revealed by VBM. Pre-HD individuals close to the onset of motor symptoms showed an increased activation of the left inferior parietal lobule and the right superior frontal gyrus compared with both pre-HD subjects far from symptom onset and healthy controls. In addition, the activation level in the left DLPFC was positively correlated with the UHDRS cognitive subscore in pre-HD subjects. Our findings demonstrate that early functional brain changes in pre-HD subjects may occur in the DLPFC before manifest cortical atrophy, and support a role of this region in the expression of clinical symptoms. Compensatory brain responses in pre-HD individuals may occur with closer proximity to the onset of manifest clinical symptoms. PMID- 17855376 TI - Neurocognitive endophenotypes of obsessive-compulsive disorder. AB - Endophenotypes (intermediate phenotypes) are objective, heritable, quantitative traits hypothesized to represent genetic risk for polygenic disorders at more biologically tractable levels than distal behavioural and clinical phenotypes. It is theorized that endophenotype models of disease will help to clarify both diagnostic classification and aetiological understanding of complex brain disorders such as obsessive-compulsive disorder (OCD). To investigate endophenotypes in OCD, we measured brain structure using magnetic resonance imaging (MRI), and behavioural performance on a response inhibition task (Stop Signal) in 31 OCD patients, 31 of their unaffected first-degree relatives, and 31 unrelated matched controls. Both patients and relatives had delayed response inhibition on the Stop-Signal task compared with healthy controls. We used a multivoxel analysis method (partial least squares) to identify large-scale brain systems in which anatomical variation was associated with variation in performance on the response inhibition task. Behavioural impairment on the Stop Signal task, occurring predominantly in patients and relatives, was significantly associated with reduced grey matter in orbitofrontal and right inferior frontal regions and increased grey matter in cingulate, parietal and striatal regions. A novel permutation test indicated significant familial effects on variation of the MRI markers of inhibitory processing, supporting the candidacy of these brain structural systems as endophenotypes of OCD. In summary, structural variation in large-scale brain systems related to motor inhibitory control may mediate genetic risk for OCD, representing the first evidence for a neurocognitive endophenotype of OCD. PMID- 17855377 TI - Stereoelectroencephalography in presurgical assessment of MRI-negative epilepsy. AB - According to most existing literature, the absence of an MRI lesion is generally associated with poorer prognosis in resective epilepsy surgery. Delineation of the epileptogenic zone (EZ) by intracranial recording is usually required but is perceived to be more difficult in 'MRI negative' cases. Most previous studies have used subdural recording and there is relatively less published data on stereoelectroencephalography (SEEG). The objective of this study was to report the experience of our group in using SEEG in presurgical evaluation, comparing its effectiveness in normal and lesional MRI cases. One hundred consecutive patients undergoing SEEG for presurgical assessment were studied. Forty-three patients out of one hundred (43%) had normal MRI and 57 (57%) had lesional MRI. Successful localization was achieved with no difference between these two groups, in 41/43 (95%) normal MRI and in 55/57 (96%) lesional MRI cases (P = 1.00). Surgery was proposed in 84/100 patients and contraindicated in 16/100 with no significant difference between lesional and MRI-negative groups (P > 0.05). At 1 year follow-up, 11/20 (55%) of those having undergone cortectomy in the MRI negative group and 21/40 (53%) in the lesional MRI group were entirely seizure free (P > 0.05) and these proportions were maintained at 2 years follow-up. Significant improvement in seizure control (ILAE outcome groups 1-4) was achieved in >90% cases with no difference between groups (P > 0.05). Of MRI-negative cases that underwent surgery, 10/23 (43%) had focal cortical dysplasia. This series showed that SEEG was equally effective in the presurgical evaluation of MRI negative and lesional epilepsies. PMID- 17855378 TI - Semaphorin 3A and 3F: key players in myelin repair in multiple sclerosis? AB - The presence of demyelinated plaques in the central nervous system is the hallmark of multiple sclerosis (MS). Some plaques remyelinate but others do not, leaving permanent damage. The reasons for this failure of repair are many, but one possible reason is the lack of migration of oligodendrocyte precursor cells to the lesion. The guidance molecules Semaphorin 3A and 3F, already known to direct oligodendroglial migration in development, may also be active in controlling oligodendrocyte precursor cell migration in MS, and hence may determine the ability of plaques to remyelinate. Here, in MS tissue and an experimental model of demyelination, we demonstrate a local source of these molecules around active demyelinating lesions, but not chronic plaques. We also provide evidence for their up-regulation at a distance from the lesion, in the neuronal cell bodies corresponding to the demyelinated axons. We propose that both of these mechanisms influence remyelination. PMID- 17855379 TI - Conservative decrease in water potential in existing leaves during new leaf expansion in temperate and tropical evergreen Quercus species. AB - BACKGROUND AND AIMS: This study aimed at clarifying how the water potential gradient (deltapsi) is maintained in the shoots of evergreen trees with expanding leaves, whose leaf water potentials at the turgor loss point (psi(tlp)) are generally high. MATERIALS: The water relations were examined in current-year expanding (CEX) and 1-year-old (OLD) leaves on the same shoots in temperate (Osaka, Japan) and tropical (Bogor, Indonesia) areas. A temperate evergreen species, Quercus glauca growing in both sites, was compared with a temperate deciduous species, Q. serrata, in Osaka, and two tropical evergreen species, Q. gemelliflora and Q. subsericea, in Bogor. KEY RESULTS: (1) In Osaka, the midday leaf water potential (psi(midday)) was slightly higher in OLD (-0.5 MPa) than in CEX leaves (-0.6 MPa), whereas psi(tlp) was significantly lower in OLD (-2.9 MPa) than in CEX leaves (-1.0 MPa). In Bogor, psi(midday) was also higher in OLD leaves (-1.0 MPa) despite the low psi(tlp) (-1.9 MPa), although stomatal conductance was not always low in OLD leaves. In the branch bearing CEX and OLD leaves, most of the hydraulic resistance (86 %) exists in the current-year branch, leading to differences in water supply between CEX and OLD leaves. The removal of buds just before breaking did not affect the high psi(midday) in OLD leaves after 1 month. Psi(midday) in OLD leaves thus appears to be independent of that in CEX leaves. CONCLUSIONS: The moderate decrease in psi(midday) in OLD leaves would contribute to maintenance of deltapsi in the shoots during leaf expansion. PMID- 17855380 TI - Mechanism and control of Solanum lycocarpum seed germination. AB - BACKGROUND AND AIMS: Solanaceae seed morphology and physiology have been widely studied but mainly in domesticated crops. The present study aimed to compare the seed morphology and the physiology of germination of Solanum lycocarpum, an important species native to the Brazilian Cerrado, with two species with endospermic seeds, tomato and coffee. METHODS: Morphological parameters of fruits and seeds were determined by microscopy. Germination was monitored for 40 d under different temperature regimes. Endosperm digestion and resistance, with endo-beta mannanase activity and required force to puncture the endosperm cap as respective markers, were measured during germination in water and in abscisic acid. KEY RESULTS: Fruits of S. lycocarpum contain dormant seeds before natural dispersion. The best germination condition found was a 12-h alternating light/dark and high/low (20/30 degrees C) temperature cycle, which seemed to target properties of the endosperm cap. The endosperm cap contains 7-8 layers of elongated polygonal cells and is predestined to facilitate radicle protrusion. The force required to puncture the endosperm cap decreased in two stages during germination and showed a significant negative correlation with endo-beta-mannanase activity. As a result of the thick endosperm cap, the puncture force was significantly higher in S. lycocarpum than in tomato and coffee. Endo-beta-mannanase activity was detected in the endosperm cap prior to radicle protrusion. Abscisic acid inhibited germination, increase of embryo weight during imbibition, the second stage of weakening of the endosperm cap and of endo-beta-mannanase activity in the endosperm cap. CONCLUSIONS: The germination mechanism of S. lycocarpum bears resemblance to that of tomato and coffee seeds. However, quantitative differences were observed in embryo pressure potential, endo-beta-mannanase activity and endosperm cap resistance that were related to germination rates across the three species. PMID- 17855381 TI - Variant-specific patterns and humoral regulation of HP1 proteins in human cells and tissues. AB - We have examined the occurrence and distribution of HP1alpha and HP1beta under in vivo, ex vivo and in vitro conditions. Consistent with a non-essential role in heterochromatin maintenance, both proteins are diminished or undetectable in several types of differentiated cells and are universally downregulated during erythropoiesis. Variant-specific patterns are observed in almost all human and mouse tissues examined. Yet, the most instructive example of HP1 plasticity is observed in the lymph nodes, where HP1alpha and HP1beta exhibit regional patterns that are exactly complementary to one another. Furthermore, whereas HP1alpha shows a dispersed sub-nuclear distribution in the majority of peripheral lymphocytes, it coalesces into large heterochromatic foci upon stimulation with various mitogens and IL-2. The effect of inductive signals on HP1alpha distribution is reproduced by coculture of immortalized T- and B-cells and can be confirmed using specific markers. These complex patterns reveal an unexpected plasticity in HP1 variant expression and strongly suggest that the sub-nuclear distribution of HP1 proteins is regulated by humoral signals and microenvironmental cues. PMID- 17855382 TI - Plasticity of HP1 proteins in mammalian cells. AB - We have compared the distribution of endogenous heterochromatin protein 1 (HP1) proteins (alpha, beta and gamma) in different epithelial lines, pluripotent stem cells and embryonic fibroblasts. In parallel, we have interrogated assembly and dynamics of newly expressed HP1-GFP proteins in cells lacking both HP1alpha and HP1beta alleles, blocked at the G1-S boundary, or cultured in the presence of HDAC and HAT inhibitors. The results reveal a range of cell type and differentiation state-specific patterns that do not correlate with 'fast' or 'slow' subunit exchange in heterochromatin. Furthermore, our observations show that targeting of HP1gamma to heterochromatic sites depends on HP1alpha and H1beta and that, on an architectural level, HP1alpha is the most polymorphic variant of the HP1 family. These data provide evidence for HP1 plasticity under shifting microenvironmental conditions and offer a new conceptual framework for understanding chromatin dynamics at the molecular level. PMID- 17855383 TI - RGS19 regulates Wnt-beta-catenin signaling through inactivation of Galpha(o). AB - The Wnt-beta-catenin pathway controls numerous cellular processes, including differentiation, cell-fate decisions and dorsal-ventral polarity in the developing embryo. Heterotrimeric G-proteins are essential for Wnt signaling, and regulator of G-protein signaling (RGS) proteins are known to act at the level of G-proteins. The functional role of RGS proteins in the Wnt-beta-catenin pathway was investigated in mouse F9 embryonic teratocarcinoma cells. RGS protein expression was investigated at the mRNA level, and each RGS protein identified was overexpressed and tested for the ability to regulate the canonical Wnt pathway. Expression of RGS19 specifically was found to attenuate Wnt-responsive gene transcription in a time- and dose-dependent manner, to block cytosolic beta catenin accumulation and Dishevelled3 (Dvl3) phosphorylation in response to Wnt3a and to inhibit Wnt-induced formation of primitive endoderm (PE). Overexpression of a constitutively active mutant of Galpha(o) rescued the inhibition of Lef-Tcf sensitive gene transcription caused by RGS19. By contrast, expression of RGS19 did not inhibit activation of Lef-Tcf gene transcription when induced in response to Dvl3 expression. However, knockdown of RGS19 by siRNA suppressed canonical Wnt signaling, suggesting a complex role for RGS19 in regulating the ability of Wnt3a to signal to the level of beta-catenin and gene transcription. PMID- 17855384 TI - Interdependency of formation and localisation of the Min complex controls symmetric plastid division. AB - Plastid division represents a fundamental biological process essential for plant development; however, the molecular basis of symmetric plastid division is unclear. AtMinE1 plays a pivotal role in selection of the plastid division site in concert with AtMinD1. AtMinE1 localises to discrete foci in chloroplasts and interacts with AtMinD1, which shows a similar localisation pattern. Here, we investigate the importance of Min protein complex formation during the chloroplast division process. Dissection of the assembly of the Min protein complex and determination of the interdependency of complex assembly and localisation in planta allow us to present a model of the molecular basis of selection of the division site in plastids. Moreover, functional analysis of AtMinE1 in bacteria demonstrates the level of functional conservation and divergence of the plastidic MinE proteins. PMID- 17855385 TI - RCC1 isoforms differ in their affinity for chromatin, molecular interactions and regulation by phosphorylation. AB - RCC1 is the guanine nucleotide exchange factor for Ran GTPase. Generation of Ran GTP by RCC1 on chromatin provides a spatial signal that directs nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. We show that RCC1 is expressed in human cells as at least three isoforms, named RCC1alpha, RCC1beta and RCC1gamma, which are expressed at different levels in specific tissues. The beta and gamma isoforms contain short inserts in their N-terminal regions (NTRs) that are not present in RCC1alpha. This region mediates interaction with chromatin, binds importin alpha3 and/or importin beta, and contains regulatory phosphorylation sites. RCC1gamma is predominantly localised to the nucleus and mitotic chromosomes like RCC1alpha. However, compared to RCC1alpha, RCC1gamma has a greatly reduced interaction with an importin alpha3 beta and a stronger interaction with chromatin that is mediated by the extended NTR. RCC1gamma is also the isoform that is most highly phosphorylated at serine 11 in mitosis. Unlike RCC1alpha, RCC1gamma supports cell proliferation in tsBN2 cells more efficiently when serine 11 is mutated to non-phosphorylatable alanine. Phosphorylation of RCC1gamma therefore specifically controls its function during mitosis. These results show that human RCC1 isoforms have distinct chromatin binding properties, different molecular interactions, and are selectively regulated by phosphorylation, as determined by their different NTRs. PMID- 17855386 TI - mDia2 regulates actin and focal adhesion dynamics and organization in the lamella for efficient epithelial cell migration. AB - Cell migration requires spatial and temporal regulation of filamentous actin (F actin) dynamics. This regulation is achieved by distinct actin-associated proteins, which mediate polymerization, depolymerization, severing, contraction, bundling or engagement to the membrane. Mammalian Diaphanous-related (mDia) formins, which nucleate, processively elongate, and in some cases bundle actin filaments, have been extensively studied in vitro, but their function in the cell has been less well characterized. Here we study the role of mDia2 activity in the dynamic organization of F-actin in migrating epithelial cells. We find that mDia2 localizes in the lamella of migrating epithelial cells, where it is involved in the formation of a stable pool of cortical actin and in maintenance of polymerization-competent free filament barbed ends at focal adhesions. Specific inhibition of mDia2 alters focal adhesion turnover and reduces migration velocity. We suggest that the regulation of filament assembly dynamics at focal adhesions may be necessary for the formation of a stable pool of cortical lamella actin and the proper assembly and disassembly dynamics of focal adhesions, making mDia2 an important factor in epithelial cell migration. PMID- 17855387 TI - Cdc42 is required for EGF-stimulated protrusion and motility in MTLn3 carcinoma cells. AB - Cdc42 plays a central role in regulating the actin cytoskeleton and maintaining cell polarity. Here, we show that Cdc42 is crucial for epidermal growth factor (EGF)-stimulated protrusion in MTLn3 carcinoma cells. When stimulated with EGF, carcinoma cells showed a rapid increase in activated Cdc42 that is primarily localized to the protruding edge of the cells. siRNA-mediated knockdown of Cdc42 expression caused a decrease in EGF-stimulated protrusion and reduced cell motility in time-lapse studies. These changes were correlated with a decrease in barbed-end formation and Arp2/3 localization at the cell edge, and a marked defect in actin filament branching, as revealed by rotary-shadowing scanning electron microscopy. Upstream of Arp2/3, Cdc42 knockdown inhibited EGF-stimulated activation of PI 3-kinase at early (within 1 minute) but not late (within 3 minutes) time points. Membrane targeting of N-WASP, WAVE2 and IRSp53 were also inhibited. Effects on WAVE2 were not owing to Rac1 inhibition, because WAVE2 recruitment is unaffected by Rac1 knockdown. Our data suggest that Cdc42 activation is crucial for the regulation of actin polymerization in carcinoma cells, and required for both EGF-stimulated protrusion and cell motility independently of effects on Rac. PMID- 17855388 TI - The endocytic control of JAK/STAT signalling in Drosophila. AB - Domeless (Dome) is an IL-6-related cytokine receptor that activates a conserved JAK/STAT signalling pathway during Drosophila development. Despite good knowledge of the signal transduction pathway in several models, the role of receptor endocytosis in JAK/STAT activation remains poorly understood. Using both in vivo genetic analysis and cell culture assays, we show that ligand binding of Unpaired 1 (Upd1) induces clathrin-dependent endocytosis of receptor-ligand complexes and their subsequent trafficking through the endosomal compartment towards the lysosome. Surprisingly, blocking trafficking in distinct endosomal compartments using mutants affecting either Clathrin heavy chain, rab5, Hrs or deep orange led to an inhibition of the JAK/STAT pathway, whereas this pathway was unchanged when rab11 was affected. This suggests that internalization and trafficking are both required for JAK/STAT activity. The requirement for clathrin-dependent endocytosis to activate JAK/STAT signalling suggests a model in which the signalling 'on' state relies not only on ligand binding to the receptor at the cell surface, but also on the recruitment of the complex into endocytic vesicles on their way to lysozomes. Selective activation of the pool of receptors marked for degradation thus provides a way to tightly control JAK/STAT activity. PMID- 17855389 TI - Do childhood sleeping problems predict obesity in young adulthood? Evidence from a prospective birth cohort study. AB - It has been suggested that sleeping problems are causally associated with obesity in early life, but most studies examining this association have been cross sectional. The authors used a population-based birth cohort of 2,494 children who were born between 1981 and 1983 in Brisbane, Australia, to examine the prospective association between early-life sleeping problems (at ages 6 months and 2-4 years) and obesity at age 21 years. The authors compared mean body mass indices (BMIs; weight (kg)/height (m)2) and persons in the categories of overweight (BMI 25.0-29.9) and obesity (BMI > or =30) among offspring at age 21 years according to maternally reported childhood sleeping problems. They found that young adult BMI and the prevalence of obesity were greater in offspring who had had sleeping problems at ages 2-4 years than in with those who had not had sleeping problems. These associations were robust to adjustment for a variety of potential confounders, including offspring sex, maternal mental health, and BMI, and several mediators, including adolescent dietary patterns and television watching. These findings provide some evidence for a long-term impact of childhood sleeping problems on the later development of obesity. PMID- 17855390 TI - Alcohol drinking, tobacco smoking, and anthropometric characteristics as risk factors for thyroid cancer: a countrywide case-control study in New Caledonia. AB - Exceptionally high incidence rates of thyroid cancer are observed in New Caledonia, particularly in Melanesian women. To investigate further the etiology of thyroid cancer and to clarify the reasons of this elevated incidence, the authors conducted a countrywide population-based case-control study in this multiethnic population. The study included 332 cases with histologically verified papillary or follicular carcinoma (293 women and 39 men) diagnosed in 1993-1999 and 412 population controls (354 women and 58 men) frequency matched by gender and 5-year age group. Thyroid cancer was negatively associated with tobacco smoking and alcohol drinking, but no inverse dose-response relation was observed. Height was positively associated with thyroid cancer, particularly in men. Strong positive associations with weight and body mass index were observed in Melanesian women aged 50 years or more, with an odds ratio of 5.5 (95% confidence interval: 1.5, 20.3) for a body mass index of 35 kg/m2 or greater compared with normal weight women, and there was a clear dose-response trend. This study clarifies the role of overweight for thyroid cancer in postmenopausal women. Because of the high prevalence of obesity among Melanesian women of New Caledonia, this finding may explain in part the exceptionally elevated incidence of thyroid cancer in this group. PMID- 17855391 TI - Objectively assessed associations between physical activity and body composition in middle-school girls: the Trial of Activity for Adolescent Girls. AB - Declining levels of physical activity probably contribute to the increasing prevalence of overweight in US youth. In this study, the authors examined cross sectional and longitudinal associations between physical activity and body composition in sixth- and eighth-grade girls. In 2003, girls were recruited from six US states as part of the Trial of Activity for Adolescent Girls. Physical activity was measured using 6 days of accelerometry, and percentage of body fat was calculated using an age- and ethnicity-specific prediction equation. Sixth grade girls with an average of 12.8 minutes of moderate-to-vigorous physical activity (MVPA) per day (15th percentile) were 2.3 times (95% confidence interval: 1.52, 3.44) more likely to be overweight than girls with 34.7 minutes of MVPA per day (85th percentile), and their percent body fat was 2.64 percentage points greater (95% confidence interval: 1.79, 3.50). Longitudinal analyses showed that percent body fat increased 0.28 percentage points less in girls with a 6.2-minute increase in MVPA than in girls with a 4.5-minute decrease (85th and 15th percentiles of change). Associations between MVPA in sixth grade and incidence of overweight in eighth grade were not detected. More population-based research using objective physical activity and body composition measurements is needed to make evidence-based physical activity recommendations for US youth. PMID- 17855392 TI - A critical three-way junction is conserved in budding yeast and vertebrate telomerase RNAs. AB - The telomerase ribonucleoprotein copies a short template within its integral RNA moiety onto eukaryotic chromosome ends, compensating for incomplete replication and degradation. Non-template regions of telomerase RNA (TER) are also crucial for telomerase function, yet they are highly divergent in sequence among species and their roles are largely unclear. Using both phylogenetic and mutational analyses, we predicted secondary structures for TERs from Kluyveromyces budding yeast species. A comparison of these secondary structure models with the published model for the Saccharomyces cerevisiae TER reveals a common arrangement into three long arms, a templating domain in the center and several conserved elements in the same positions within the structure. One of them, a three-way junction element, is highly conserved in budding yeast TERs. This element also shows sequence and structure similarity to the critical CR4-CR5 activating domain of vertebrate TERs. Mutational analysis in Kluyveromyces lactis confirmed that this element, and in particular the residues conserved across yeast and vertebrates, is critical for telomerase action both in vivo and in vitro. These findings demonstrate that despite the extreme divergence of TER sequences from different organisms, they do share conserved elements, which presumably carry out common roles in telomerase function. PMID- 17855393 TI - Deletion of the nuclear exosome component RRP6 leads to continued accumulation of the histone mRNA HTB1 in S-phase of the cell cycle in Saccharomyces cerevisiae. AB - The nuclear exosome, a macromolecular complex of 3' to 5' exonucleases, is required for the post-transcriptional processing of a variety of RNAs including rRNAs and snoRNAs. Additionally, this complex forms part of a nuclear surveillance network where it acts to degrade any aberrantly processed mRNAs in the nucleus. The exosome complex has been implicated in the biogenesis pathway of general messenger RNAs through its interaction with the 3'-end processing machinery. During the cell cycle, yeast histone mRNAs accumulate in the S-phase and are rapidly degraded as cells enter the G2-phase. To determine if the exosome contributes to the cyclic turnover of yeast histone mRNAs, we examined the pattern of accumulation of 'HTB1' mRNA during the cell cycle in a deletion strain of 'RRP6', a component of the nuclear exosome. Our results show that cells lacking Rrp6p continue to accumulate HTB1 mRNA as the cell cycle proceeds. This continued accumulation appears to result from a delay in exit from S-phase in rrp6 cells. The accumulation of HTB1 mRNA in rrp6 cells is influenced by the interaction of the nuclear exosome with the 3'-end processing machinery although there is no evidence for differential regulation of histone mRNA 3'-end processing during the yeast cell cycle. PMID- 17855394 TI - Structure-function study of maize ribosome-inactivating protein: implications for the internal inactivation region and the sole glutamate in the active site. AB - Maize ribosome-inactivating protein is classified as a class III or an atypical RNA N-glycosidase. It is synthesized as an inactive precursor with a 25-amino acid internal inactivation region, which is removed in the active form. As the first structural example of this class of proteins, crystals of the precursor and the active form were diffracted to 2.4 and 2.5 A, respectively. The two proteins are similar, with main chain root mean square deviation (RMSD) of 0.519. In the precursor, the inactivation region is found on the protein surface and consists of a flexible loop followed by a long alpha-helix. This region diminished both the interaction with ribosome and cytotoxicity, but not cellular uptake. Like bacterial ribosome-inactivating proteins, maize ribosome-inactivating protein does not have a back-up glutamate in the active site, which helps the protein to retain some activity if the catalytic glutamate is mutated. The structure reveals that the active site is too small to accommodate two glutamate residues. Our structure suggests that maize ribosome-inactivating protein may represent an intermediate product in the evolution of ribosome-inactivating proteins. PMID- 17855395 TI - Novel rapidly evolving hominid RNAs bind nuclear factor 90 and display tissue restricted distribution. AB - Nuclear factor 90 (NF90) is a double-stranded RNA-binding protein implicated in multiple cellular functions, but with few identified RNA partners. Using in vivo cross-linking followed by immunoprecipitation, we discovered a family of small NF90-associated RNAs (snaR). These highly structured non-coding RNAs of approximately 117 nucleotides are expressed in immortalized human cell lines of diverse lineages. In human tissues, they are abundant in testis, with minor distribution in brain, placenta and some other organs. Two snaR subsets were isolated from human 293 cells, and additional species were found by bioinformatic analysis. Their genes often occur in multiple copies arranged in two inverted regions of tandem repeats on chromosome 19. snaR-A is transcribed by RNA polymerase III from an intragenic promoter, turns over rapidly, and shares sequence identity with Alu RNA and two potential piRNAs. It interacts with NF90's double-stranded RNA-binding motifs. snaR orthologs are present in chimpanzee but not other mammals, and include genes located in the promoter of two chorionic gonadotropin hormone genes. snaRs appear to have undergone accelerated evolution and differential expansion in the great apes. PMID- 17855396 TI - Catalytic domain of restriction endonuclease BmrI as a cleavage module for engineering endonucleases with novel substrate specificities. AB - Creating endonucleases with novel sequence specificities provides more possibilities to manipulate DNA. We have created a chimeric endonuclease (CH endonuclease) consisting of the DNA cleavage domain of BmrI restriction endonuclease and C.BclI, a controller protein of the BclI restriction modification system. The purified chimeric endonuclease, BmrI198-C.BclI, cleaves DNA at specific sites in the vicinity of the recognition sequence of C.BclI. Double-strand (ds) breaks were observed at two sites: 8 bp upstream and 18 bp within the C-box sequence. Using DNA substrates with deletions of C-box sequence, we show that the chimeric endonuclease requires the 5' half of the C box only for specific cleavage. A schematic model is proposed for the mode of protein-DNA binding and DNA cleavage. The present study demonstrates that the BmrI cleavage domain can be used to create combinatorial endonucleases that cleave DNA at specific sequences dictated by the DNA-binding partner. The resulting endonucleases will be useful in vitro and in vivo to create ds breaks at specific sites and generate deletions. PMID- 17855397 TI - Genomic profiling of CpG methylation and allelic specificity using quantitative high-throughput mass spectrometry: critical evaluation and improvements. AB - CpG methylation is a key component of the epigenome architecture that is associated with changes in gene expression without a change to the DNA sequence. Since the first reports on deregulation of DNA methylation, in diseases such as cancer, and the initiation of the Human Epigenome Project, an increasing need has arisen for a detailed, high-throughput and quantitative method of analysis to discover and validate normal and aberrant DNA methylation profiles in large sample cohorts. Here we present an improved protocol using base-specific fragmentation and MALDI-TOF mass spectrometry that enables a sensitive and high throughput method of DNA methylation analysis, quantitative to 5% methylation for each informative CpG residue. We have determined the accuracy, variability and sensitivity of the protocol, implemented critical improvements in experimental design and interpretation of the data and developed a new formula to accurately measure CpG methylation. Key innovations now permit determination of differential and allele-specific methylation, such as in cancer and imprinting. The new protocol is ideally suitable for detailed DNA methylation analysis of multiple genomic regions and large sample cohorts that is critical for comprehensive profiling of normal and diseased human epigenomes. PMID- 17855398 TI - A UTF1-based selection system for stable homogeneously pluripotent human embryonic stem cell cultures. AB - Undifferentiated transcription factor 1 (UTF1) was identified first in mouse embryonic stem cells and is also expressed in human embryonic and adult stem cells. UTF1 transcription ceases at the onset of differentiation, which clearly distinguishes it from less sensitive pluripotency markers, such as Oct4 or Nanog. We present here two transgenic hESC lines, named ZUN. Each line harbors one copy of the UTF1 promoter/enhancer driving a resistance gene and yielded highly homogeneous cultures under selection pressure, with a larger proportion of Oct4 and Sox2 positive cells. While ZUN cultures, like parental HUES8 cultures, retained the capacity to differentiate into tissues of all three germ layers using a SICD mouse teratoma model, they surprisingly exhibited an increased refractoriness to various differentiation cues in vitro. Together with its small size of only 2.4 kb for the entire cassette, these features render our selection system a powerful novel tool for many stem cell applications and human somatic cell reprogramming strategies. PMID- 17855399 TI - MALISAM: a database of structurally analogous motifs in proteins. AB - MALISAM (manual alignments for structurally analogous motifs) represents the first database containing pairs of structural analogs and their alignments. To find reliable analogs, we developed an approach based on three ideas. First, an insertion together with a part of the evolutionary core of one domain family (a hybrid motif) is analogous to a similar motif contained within the core of another domain family. Second, a motif at an interface, formed by secondary structural elements (SSEs) contributed by two or more domains or subunits contacting along that interface, is analogous to a similar motif present in the core of a single domain. Third, an artificial protein obtained through selection from random peptides or in sequence design experiments not biased by sequences of a particular homologous family, is analogous to a structurally similar natural protein. Each analogous pair is superimposed and aligned manually, as well as by several commonly used programs. Applications of this database may range from protein evolution studies, e.g. development of remote homology inference tools and discriminators between homologs and analogs, to protein-folding research, since in the absence of evolutionary reasons, similarity between proteins is caused by structural and folding constraints. The database is publicly available at http://prodata.swmed.edu/malisam. PMID- 17855400 TI - DNA sequencing: bench to bedside and beyond. AB - Fifteen years elapsed between the discovery of the double helix (1953) and the first DNA sequencing (1968). Modern DNA sequencing began in 1977, with development of the chemical method of Maxam and Gilbert and the dideoxy method of Sanger, Nicklen and Coulson, and with the first complete DNA sequence (phage X174), which demonstrated that sequence could give profound insights into genetic organization. Incremental improvements allowed sequencing of molecules >200 kb (human cytomegalovirus) leading to an avalanche of data that demanded computational analysis and spawned the field of bioinformatics. The US Human Genome Project spurred sequencing activity. By 1992 the first 'sequencing factory' was established, and others soon followed. The first complete cellular genome sequences, from bacteria, appeared in 1995 and other eubacterial, archaebacterial and eukaryotic genomes were soon sequenced. Competition between the public Human Genome Project and Celera Genomics produced working drafts of the human genome sequence, published in 2001, but refinement and analysis of the human genome sequence will continue for the foreseeable future. New 'massively parallel' sequencing methods are greatly increasing sequencing capacity, but further innovations are needed to achieve the 'thousand dollar genome' that many feel is prerequisite to personalized genomic medicine. These advances will also allow new approaches to a variety of problems in biology, evolution and the environment. PMID- 17855401 TI - Differentiation of core promoter architecture between plants and mammals revealed by LDSS analysis. AB - Mammalian promoters are categorized into TATA and CpG-related groups, and they have complementary roles associated with differentiated transcriptional characteristics. While the TATA box is also found in plant promoters, it is not known if CpG-type promoters exist in plants. Plant promoters contain Y Patches (pyrimidine patches) in the core promoter region, and the ubiquity of these beyond higher plants is not understood as well. Sets of promoter sequences were utilized for the analysis of local distribution of short sequences (LDSS), and approximately one thousand octamer sequences have been identified as promoter constituents from Arabidopsis, rice, human and mouse, respectively. Based on their localization profiles, the identified octamer sequences were classified into several major groups, REG (Regulatory Element Group), TATA box, Inr (Initiator), Kozak, CpG and Y Patch. Comparison of the four species has revealed three categories: (i) shared groups found in both plants and mammals (TATA box), (ii) common groups found in both kingdoms but the utilized sequence is differentiated (REG, Inr and Kozak) and (iii) specific groups found in either plants or mammals (CpG and Y Patch). Our comparative LDSS analysis has identified conservation and differentiation of promoter architectures between higher plants and mammals. PMID- 17855402 TI - The human checkpoint sensor Rad9-Rad1-Hus1 interacts with and stimulates DNA repair enzyme TDG glycosylase. AB - Human (h) DNA repair enzyme thymine DNA glycosylase (hTDG) is a key DNA glycosylase in the base excision repair (BER) pathway that repairs deaminated cytosines and 5-methyl-cytosines. The cell cycle checkpoint protein Rad9-Rad1 Hus1 (the 9-1-1 complex) is the surveillance machinery involved in the preservation of genome stability. In this study, we show that hTDG interacts with hRad9, hRad1 and hHus1 as individual proteins and as a complex. The hHus1 interacting domain is mapped to residues 67-110 of hTDG, and Val74 of hTDG plays an important role in the TDG-Hus1 interaction. In contrast to the core domain of hTDG (residues 110-308), hTDG(67-308) removes U and T from U/G and T/G mispairs, respectively, with similar rates as native hTDG. Human TDG activity is significantly stimulated by hHus1, hRad1, hRad9 separately, and by the 9-1-1 complex. Interestingly, the interaction between hRad9 and hTDG, as detected by co immunoprecipitation (Co-IP), is enhanced following N-methyl-N'-nitro-N nitrosoguanidine (MNNG) treatment. A significant fraction of the hTDG nuclear foci co-localize with hRad9 foci in cells treated with methylating agents. Thus, the 9-1-1 complex at the lesion sites serves as both a damage sensor to activate checkpoint control and a component of the BER. PMID- 17855403 TI - Dynamic interactions within sub-complexes of the H/ACA pseudouridylation guide RNP. AB - H/ACA RNP complexes change uridines to pseudouridines in target non-coding RNAs in eukaryotes and archaea. H/ACA RNPs are comprised of a guide RNA and four essential proteins: Cbf5 (pseudouridine synthase), L7Ae, Gar1 and Nop10 in archaea. The guide RNA captures the target RNA via two antisense elements brought together to form a contiguous binding site within the pseudouridylation pocket (internal loop) of the guide RNA. Cbf5 and L7Ae interact independently with the guide RNA, and here we have examined the impacts of these proteins on the RNA in nucleotide protection assays. The results indicate that the interactions observed in a fully assembled H/ACA RNP are established in the sub-complexes, but also reveal a unique Cbf5-guide RNA interaction that is displaced by L7Ae. In addition, the results indicate that L7Ae binding at the kink (k)-turn of the guide RNA induces the formation of the upper stem, and thus also the pseudouridylation pocket. Our findings indicate that L7Ae is essential for formation of the substrate RNA binding site in the archaeal H/ACA RNP, and suggest that k-turn-binding proteins may remodel partner RNAs with important effects distant from the protein-binding site. PMID- 17855404 TI - A study of 7-deaza-2'-deoxyguanosine 2'-deoxycytidine base pairing in DNA. AB - The incorporation of 7-deazaguanine modifications into DNA is frequently used to probe protein recognition of H-bonding information in the major groove of DNA. While it is generally assumed that 7-deazaguanine forms a normal Watson-Crick base pair with cytosine, detailed thermodynamic and structural analyses of this modification have not been reported. The replacement of the 7-N atom on guanine with a C-H, alters the electronic properties of the heterocycle and eliminates a major groove cation-binding site that could affect the organization of salts and water in the major groove. We report herein the characterization of synthetic DNA oligomers containing 7-deazaguanine using a variety of complementary approaches: UV thermal melting, differential scanning calorimetry (DSC), circular dichroism (CD), chemical probing and NMR. The results indicate that the incorporation of a 7-deazaguanine modification has a significant effect on the dynamic structure of the DNA at the flanking residue. This appears to be mediated by changes in hydration and cation organization. PMID- 17855405 TI - Concentrations and significance of cytokines and other immunologic factors in semen of healthy fertile men. AB - BACKGROUND: The purpose of this study was to establish normal reference values for several immunologic factors in semen to provide a foundation for understanding their physiologic significance in health and disease. METHODS: Semen from 83 healthy, fertile men was assessed by Bio-Plex or enzyme-linked immunosorbent assay to determine quantities of immunoglobulin (Ig) isotypes, chemokines, cytokines and growth factors. We also enumerated polymorphonuclear granulocytes (PMN) by peroxidase staining to examine the association of inflammation with levels of these factors. RESULTS: High concentrations of IgG and IgA were detected in all samples. IgG concentrations were significantly higher than IgA concentrations (P < 0.0001). Likewise, two multifunctional growth factors, transforming growth factor-beta1 and interleukin (IL)-7, and three chemokines, stromal cell-derived factor-1alpha, monocyte chemotactic/chemoattractant protein-1 and IL-8, were present in high concentrations in all samples (medians >1000 pg/ml). Other soluble factors were detectable in low concentration (medians <150 pg/ml), either in a majority of samples [IL-1alpha and beta, IL-5, IL-6, IL-13, IL-17, regulated on activation normal T cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1beta, interferon (IFN)-alpha and granulocyte colony-stimulating factor (CSF)], or in a minority of samples (MIP-1alpha, IL-2, IL-10, IL-12, TNF-alpha, IFN-gamma and granulocyte-macrophage-CSF). PMN counts significantly correlated with IL-1beta, IL-6, TNF-alpha, MIP-1alpha, MIP-1beta, IL-13 and IgA concentrations. CONCLUSIONS: The semen of healthy, fertile men contains a broad array of immunologic factors. These normative values can serve as a foundation for future studies on the role of these factors in infertility, genital tract infections and other pathologic conditions. PMID- 17855406 TI - The diagnostic effectiveness of an initial transvaginal scan in detecting ectopic pregnancy. AB - BACKGROUND: To determine the effectiveness of an initial transvaginal ultrasound scan (TVS) in the detection of ectopic pregnancy in consecutive women attending an early pregnancy unit (EPU). METHODS: This was a prospective observational study. Unselected women attending a dedicated EPU underwent a TVS. Women were classified as having an intrauterine pregnancy (IUP), ectopic pregnancy or pregnancy of unknown location (PUL). Women with a PUL were followed up until the final location of the pregnancy was determined. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) with 95% confidence intervals (CIs) for the initial TVS in the diagnosis of ectopic pregnancy were calculated. RESULTS: During a one-year study period, 5318 consecutive women attended the EPU. Outcome data were available for 5240 (98.5%) women. Of these, the initial TVS showed an IUP in 4693 (89.6%) cases and an ectopic pregnancy in 91 (1.7%) cases. The remaining 456 (8.7%) women were classified as PUL, and of these 31 (6.8%) were subsequently found to have ectopic pregnancies. The overall sensitivity of the initial TVS in the diagnosis of ectopic pregnancy was 73.9% (95% CI: 65.1-81.6) with a specificity of 99.9% (95% CI: 99.8-100), a PPV of 96.7% (95% CI: 90.7-99.3) and an NPV of 99.4% (95% CI: 99.2-99.6). CONCLUSIONS: In unselected women attending an EPU, pregnancy location can be diagnosed accurately in over 90% of all pregnancies and in 73.9% of ectopic pregnancies with a single TVS. PMID- 17855407 TI - Diagnostic potential of serum N-terminal pro-B-type brain natriuretic peptide level in detection of cardiac wall stress in women with polycystic ovary syndrome: a cross-sectional comparison study. AB - BACKGROUND: In addition to the negative effect on fertility, polycystic ovary syndrome (PCOS) has been associated with cardiac pathology. Brain natriuretic peptide (BNP) is a possible marker for cardiac risk, therefore we investigated whether N-terminal pro-B-type BNP (NT-proBNP) increases in women with PCOS compared with healthy women of comparable age and body mass index. METHODS: Thirty women with PCOS and 30 healthy women not suffering from overt cardiac disease were involved in the study. Fasting insulin and serum NT-proBNP levels were measured, and M-Mode echocardiography was performed. Insulin resistance was calculated using the homeostasis model assessment insulin resistance index (HOMA IR). RESULTS: PCOS subjects had higher NT-proBNP levels than the control subjects (P < 0.001). Abnormal echocardiography indices were detected in 14 of the PCOS subjects (but none of the controls), including valvular heart disease in nine, diastolic dysfunction in two, right ventricular enlargement in one, right atrial enlargement in one and pulmonary hypertension in one. PCOS subjects (n = 30) showed an increased left ventricular mass (LVM) (P < 0.001) and left ventricular posterior wall thickness (LVPWT) (P = 0.006). In addition, NT-proBNP concentration was positively correlated with LVM (r = 0.587, P = 0.001) and negatively correlated with sex-hormone-binding globulin (r = -0.528, P = 0.003). There was a positive correlation between LVM and HOMA-IR (r = 0.295, P = 0.03) while LVPWT was positively correlated with fasting insulin and HOMA-IR (r = 0.335, P = 0.031 and r = 0.346, P = 0.045, respectively) in PCOS subjects (n = 30). CONCLUSION: The present study demonstrated that the level of NT-proBNP was increased in PCOS subjects with asymptomatic heart disease. PMID- 17855408 TI - The risk of cancer and the role of parity among women with endometriosis. AB - BACKGROUND: Several epidemiological studies have shown an increased cancer risk among women with endometriosis, especially ovarian cancer. Infertility and nulliparity are also known risk factors for different types of cancer. The aim of this study is to investigate cancer risk among women with endometriosis, stratifying for parity. METHODS: Women discharged from a hospital, with the diagnosis of endometriosis from 1969 to 2002, were identified using the National Swedish Inpatient Register. Data were linked to the National Swedish Cancer Register to identify cases of cancer and to the Swedish Multi-Generation Register to calculate parity and age at first birth. Standardized incidence ratios (SIR) were calculated. RESULTS: A total of 63,630 women entered the study. To exclude cancers already present at the time of endometriosis diagnosis, the first year of follow-up was excluded, leaving a number of 3,822 cases of cancer. There was no increased overall risk of cancer (SIR 1.01) among women with endometriosis. Endometriosis was associated with elevated risks for endocrine tumours (SIR 1.38), ovarian cancer (SIR 1.37), renal cancer (SIR 1.36), thyroid cancer (SIR 1.33), brain tumours (SIR 1.27), malignant melanoma (SIR 1.23) and breast cancer (SIR 1.08), as well as a reduced risk for cervical cancer (SIR 0.71). There were no significant differences between nulliparous and parous women with endometriosis regarding cancer risk for any of the cancer types. There was a non significant decrease in risk of ovarian cancer with increasing parity for women with endometriosis. CONCLUSIONS: Women with endometriosis have an increased risk for several malignancies. The increased risks do not seem to be related to parity. PMID- 17855409 TI - The ISMAAR proposal on terminology for ovarian stimulation for IVF. AB - IVF is performed with oocytes collected in natural and stimulated cycles. Different approaches to ovarian stimulation have been employed worldwide. Following the introduction of GnRH antagonists and strategies to reduce multiple births such as single embryo transfer, there is a genuine scientific interest in the revival of natural cycle and mild approaches to ovarian stimulation in IVF. Recent evidence suggests that application of natural and mild IVF is patient centred, aimed at reducing the cost of treatment, patient discomfort and multiple pregnancies. However, there seems to be no consistency in the terminology used for definitions and protocols for ovarian stimulation in IVF cycles. Following the recent International Society for Mild Approaches in Assisted Reproduction (ISMAAR) meeting and communication with interested international experts, this article has recommended revised definitions and terminology for natural cycle IVF and different protocols used in ovarian stimulation for IVF. It is proposed that these terms are adopted internationally in order to achieve a consistency in clinical practice, research publications and communication with patients. PMID- 17855410 TI - Re: Vascular endothelial growth factor production by circulating immune cells is elevated in ovarian hyperstimulation syndrome. PMID- 17855411 TI - Endometrial receptivity after oocyte donation in recipients with a history of chemotherapy and/or radiotherapy. AB - INTRODUCTION: Information is scarce regarding the outcome of oocyte donation (OD) in patients with a history of cancer treatment. Therefore, we conducted a matched controlled analysis on the outcome of OD in these recipients. METHODS: Between January 2000 and November 2005, 33 patients with a history of chemotherapy and/or radiotherapy had an OD cycle. Matching was performed to the chronologically closest patient without a history of cancer therapy by number of days of hormonal stimulation before embryo replacement, number of replaced embryos, day of embryo transfer and origin of sperm. RESULTS: The primary diseases of the patients were Hodgkin's lymphoma (n = 12), non-Hodgkin's lymphoma (n = 3), leukaemia (n = 7), ovarian cancer (n = 6), Ewing's sarcoma (n = 2), breast cancer (n = 1), sympathoblastoma (n = 1) and histiocytosis X (n = 1). Twenty-three patients had undergone chemotherapy and radiotherapy, nine patients chemotherapy only and one radiotherapy only. The mean age of the recipients was 33.1 years [95% confidence interval (CI) 30.9-35.3] and 39.6 (95% CI 37.1-42.1) in the study and control groups, respectively. The average number of received oocytes and transferred embryos, was similar in both groups. Nineteen (57.6%) versus 13 (39.4%) pregnancies resulting in an ongoing pregnancy (i.e. viable at 12 weeks) in 15 (45.4%) versus 9 cycles (27.3%) (NS) were obtained in study and control groups, respectively. Implantation rate in study and control groups was 35.8 versus 17.9%, respectively (P = 0.02). CONCLUSIONS: The results suggest that patients with a history of cancer treatment have a pregnancy rate after OD similar to that in the general population of oocyte recipients. PMID- 17855412 TI - Differences in ovarian function parameters between Chinese and Caucasian oocyte donors: do they offer an explanation for lower IVF pregnancy rates in Chinese women? AB - BACKGROUND: IVF outcomes in Chinese women are inferior to those of Caucasian patients. Reflecting prematurely diminished ovarian function, women with elevated age-specific baseline (b-) FSH levels are designated to suffer from premature ovarian aging (POA). We investigated if the prevalence of POA differs between these two ethnic populations. METHODS: We compared patient characteristics and first IVF cycle outcomes in 29 consecutive, Caucasian and 17 Asian-Chinese oocyte donors. POA was diagnosed in a donor if her b-FSH levels exceeded the 95% confidence interval (CI) for her age group. RESULTS: There was no age difference between Chinese and Caucasian groups (26.2 +/- 4.9 versus 25.7 +/- 3.1 years, respectively). Chinese women demonstrated, however, a higher cycle cancellation rate (5/17, 29.4%), either before cycle start or during stimulation (0/29; relative risk 1.42, 95% CI 1.04-1.9; P < 0.01), fewer oocytes per initiated cycle (9.3 +/- 9.7 versus 15.3 +/- 7.1, respectively; P < 0.05) (difference disappeared for only cycles that reached retrieval) and higher b-FSH levels (7.5 +/- 1.9 versus 5.1 +/- 1.7 mIU/ml, respectively; P = 0.004). Nine out of 17 (53%) of Chinese and only 1/26 (4%) of Caucasian donors met b-FSH level criteria for a presumptive POA diagnosis. Their odds of meeting POA criteria were approximately 30-times greater (odds ratio 31.5; 95% CI 3.5-18.7; P < 0.0001). CONCLUSIONS: These data suggest a possible explanation for lower IVF pregnancy rates in Chinese women. Preceding treatment, Chinese women at all ages should be carefully investigated to detect occult POA. Ethnicity may have to be considered an additional outcome variable in fertility studies. PMID- 17855413 TI - HIV-1 viral DNA is present in ejaculated abnormal spermatozoa of seropositive subjects. AB - BACKGROUND: Semen is the major vehicle for HIV-1 infection as it contains free and cell-associated virions and infected cells. However, the presence of HIV-1 in spermatozoa has been a matter of debate, since the sperm cell fraction may contain somatic infected cells that jeopardize the attribution of the detected virus to the spermatozoa. METHODS: Spermatozoa from 12 HIV-1 seropositive subjects were purified by multilayered Percoll gradient followed by osmotic shock. Residual presence of non-seminal cells (NCS) in purified spermatozoa, was then evaluated by cytometric and molecular analysis. HIV-1 DNA was revealed by nested PCR and in situ PCR after sperm chromatin decondensation. DNA-fragmented ejaculated spermatozoa in semen of infected subjects were detected by terminal deoxynucleotidyl transferase-mediated dUDP nick-end labeling (TUNEL) analysis. RESULTS: Purification procedure adopted allowed complete removal of NCS. On purified sperm cells, HIV-1 DNA was detected in 5 out of 12 subjects by nested PCR. On crude semen of 10 out of 12 subjects, HIV-1 DNA was in situ detected in a small percentage of abnormal spermatozoa with a wide range of structural alterations. TUNEL analysis revealed an increased percentage of DNA-fragmented ejaculated spermatozoa in semen of infected subjects. CONCLUSIONS: We report molecular evidence demonstrating that HIV-1 infected subjects can ejaculate small amounts of HIV-1 DNA-positive abnormal spermatozoa. Their possible role in HIV-1 sexual transmission remains to be clarified. PMID- 17855414 TI - Total endoscopic repair of a pediatric atrial septal defect using the da Vinci robot and hypothermic fibrillation. AB - Computerized robotic enhancement has recently emerged as a promising technology to facilitate minimally invasive cardiac surgery. We report the first totally endoscopic closure of an atrial septal defect in a child using the da Vinci robot and hypothermic fibrillation. PMID- 17855415 TI - Functional profiling of microarray experiments using text-mining derived bioentities. AB - MOTIVATION: The increasing use of microarray technologies brought about a parallel demand in methods for the functional interpretation of the results. Beyond the conventional functional annotations for genes, such as gene ontology, pathways, etc. other sources of information are still to be exploited. Text mining methods allow extracting informative terms (bioentities) with different functional, chemical, clinical, etc. meanings, that can be associated to genes. We show how to use these associations within an appropriate statistical framework and how to apply them through easy-to-use, web-based environments to the functional interpretation of microarray experiments. Functional enrichment and gene set enrichment tests using bioentities are presented. PMID- 17855416 TI - RagPools: RNA-As-Graph-Pools--a web server for assisting the design of structured RNA pools for in vitro selection. AB - SUMMARY: Our RNA-As-Graph-Pools (RagPools) web server offers a theoretical companion tool for RNA in vitro selection and related problems. Specifically, it suggests how to construct RNA sequence/structure pools with user-specified properties and assists in analyzing resulting distributions. This utility follows our recently developed approach for engineering sequence pools that links RNA sequence space regions with corresponding structural distributions via a 'mixing matrix' approach combined with a graph theory analysis of RNA secondary-structure space; the mixing matrix specifies nucleotide transition rates, and graph theory links sequences to simple graphical objects representing RNA motifs. The companion RagPools web server ('Designer' component) provides optimized starting sequences, mixing matrices and associated weights in response to a user-specified target pool structure distribution. In addition, RagPools ('Analyzer' component) analyzes the motif distribution of pools generated from user-specified starting sequences and mixing matrices. Thus, RagPools serves as a guide to researchers who aim to synthesize RNA pools with desired properties and/or experiment in silico with various designs by our approach. AVAILABILITY: The web server is accessible on the web at http://rubin2.biomath.nyu.edu PMID- 17855417 TI - Evolutionary analysis of enzymes using Chisel. AB - MOTIVATION: Availability of large volumes of genomic and enzymatic data for taxonomically and phenotypically diverse organisms allows for exploration of the adaptive mechanisms that led to diversification of enzymatic functions. We present Chisel, a computational framework and a pipeline for an automated, high resolution analysis of evolutionary variations of enzymes. Chisel allows automatic as well as interactive identification, and characterization of enzymatic sequences. Such knowledge can be utilized for comparative genomics, microbial diagnostics, metabolic engineering, drug design and analysis of metagenomes. RESULTS: Chisel is a comprehensive resource that contains 8575 clusters and subsequent computational models specific for 939 distinct enzymatic functions and, when data is sufficient, their taxonomic variations. Application of Chisel to identification of enzymatic sequences in newly sequenced genomes, analysis of organism-specific metabolic networks, 'binning' of metagenomes and other biological problems are presented. We also provide a thorough analysis of Chisel performance with other similar resources and manual annotations on Shewanella oneidensis MR1 genome. PMID- 17855418 TI - Cyto-Sim: a formal language model and stochastic simulator of membrane-enclosed biochemical processes. AB - MOTIVATION: Compartments and membranes are the basis of cell topology and more than 30% of the human genome codes for membrane proteins. While it is possible to represent compartments and membrane proteins in a nominal way with many mathematical formalisms used in systems biology, few, if any, explicitly model the topology of the membranes themselves. Discrete stochastic simulation potentially offers the most accurate representation of cell dynamics. Since the details of every molecular interaction in a pathway are often not known, the relationship between chemical species in not necessarily best described at the lowest level, i.e. by mass action. Simulation is a form of computer-aided analysis, relying on human interpretation to derive meaning. To improve efficiency and gain meaning in an automatic way, it is necessary to have a formalism based on a model which has decidable properties. RESULTS: We present Cyto-Sim, a stochastic simulator of membrane-enclosed hierarchies of biochemical processes, where the membranes comprise an inner, outer and integral layer. The underlying model is based on formal language theory and has been shown to have decidable properties (Cavaliere and Sedwards, 2006), allowing formal analysis in addition to simulation. The simulator provides variable levels of abstraction via arbitrary chemical kinetics which link to ordinary differential equations. In addition to its compact native syntax, Cyto-Sim currently supports models described as Petri nets, can import all versions of SBML and can export SBML and MATLAB m-files. AVAILABILITY: Cyto-Sim is available free, either as an applet or a stand-alone Java program via the web page (http://www.cosbi.eu/Rpty_Soft_CytoSim.php). Other versions can be made available upon request. PMID- 17855419 TI - Accurate prediction of deleterious protein kinase polymorphisms. AB - MOTIVATION: Contemporary, high-throughput sequencing efforts have identified a rich source of naturally occurring single nucleotide polymorphisms (SNPs), a subset of which occur in the coding region of genes and result in a change in the encoded amino acid sequence (non-synonymous coding SNPs or 'nsSNPs'). It is hypothesized that a subset of these nsSNPs may underlie common human disease. Testing all these polymorphisms for disease association would be time consuming and expensive. Thus, computational methods have been developed to both prioritize candidate nsSNPs and make sense of their likely molecular physiologic impact. RESULTS: We have developed a method to prioritize nsSNPs and have applied it to the human protein kinase gene family. The results of our analyses provide high quality predictions and outperform available whole genome prediction methods (74% versus 83% prediction accuracy). Our analyses and methods consider both DNA sequence conservation, which most traditional methods are based on, as well unique structural and functional features of kinases. We provide a ranked list of common kinase nsSNPs that have a higher probability of impacting human disease based on our analyses. PMID- 17855420 TI - AVIS: AJAX viewer of interactive signaling networks. AB - MOTIVATION: Increasing complexity of cell signaling network maps requires sophisticated visualization technologies. Simple web-based visualization tools can allow for improved data presentation and collaboration. Researchers studying cell signaling would benefit from having the ability to embed dynamic cell signaling maps in web pages. SUMMARY: AVIS is a Google gadget compatible web based viewer of interactive cell signaling networks. AVIS is an implementation of AJAX (Asynchronous JavaScript with XML) with the usage of the libraries GraphViz, ImageMagic (PerlMagic) and overLib. AVIS provides web-based visualization of text based signaling networks with dynamical zooming, panning and linking capabilities. AVIS is a cross-platform web-based tool that can be used to visualize network maps as embedded objects in any web page. AVIS was implemented for visualization of PathwayGenerator, a tool that displays over 4000 automatically generated mammalian cell signaling maps; NodeNeighborhood a tool to visualize first and second interacting neighbors of yeast and mammalian proteins; and for Genes2Networks, a tool to connect lists of genes and protein using background protein interaction networks. AVAILABILITY: A demo page of AVIS and links to applications and distributions can be found at http://actin.pharm.mssm.edu/AVIS2. Detailed instructions for using and configuring AVIS can be found in the user manual at http://actin.pharm.mssm.edu/AVIS2/manual.pdf. PMID- 17855421 TI - FIST: a sensory domain for diverse signal transduction pathways in prokaryotes and ubiquitin signaling in eukaryotes. AB - MOTIVATION: Sensory domains that are conserved among Bacteria, Archaea and Eucarya are important detectors of common signals detected by living cells. Due to their high sequence divergence, sensory domains are difficult to identify. We systematically look for novel sensory domains using sensitive profile-based searches initiated with regions of signal transduction proteins where no known domains can be identified by current domain models. RESULTS: Using profile searches followed by multiple sequence alignment, structure prediction and domain architecture analysis, we have identified a novel sensory domain termed FIST, which is present in signal transduction proteins from Bacteria, Archaea and Eucarya. Chromosomal proximity of FIST-encoding genes to those coding for proteins involved in amino acid metabolism and transport suggest that FIST domains bind small ligands, such as amino acids. PMID- 17855422 TI - Diseases of the kidney in medieval Persia the--Hidayat of Al-Akawayni. AB - The centralization of socioeconomic resources following the rise of the Islamic empire in the 7th century nurtured an initial gathering and translation into Arabic of extant medical texts in Greek, Syriac, Hindu and Chinese. As Arabic became the lingua franca of scholarship, there followed a second period of assimilation, original observations, commentary and systematization of medical knowledge in Arabic texts, which became the basis of revival and learned medicine in the West in the 12th century. However, not all medical texts of the period were written in Arabic. As central power eroded, provincial principalities arose, and regional cultures flourished, medical texts began to be written in local dialects, particularly in Persia. Notable amongst those and probably the oldest is the Hidayat al-Muallimin fi-al-Tibb (Learner's; guide to medicine) written by Abubakr al-Akawayni al-Bokhari in the closing decades of the 10th century. Written in Farsi and dedicated to his son and other students of medicine, the Hidayat is a relatively short and simplified pandect of medicine at the time and provides a glimpse of the teaching of medicine of the period. The present article is a translation of the sections of the Hidayat related to the kidney and urinary tract and their diseases. These early writings provide insight into the care of patients with kidney disease during the Middle Ages in general, and in Persia in particular. PMID- 17855424 TI - Lack of association of the -463 G/A myeloperoxidase promoter polymorphism with Behcet's disease in Italian patients. AB - OBJECTIVE: To investigate potential associations between the -463 G/A myeloperoxidase (MPO) promoter polymorphism and susceptibility to, and clinical expression of, Behcet's disease (BD). METHODS: One hundred and seventy-five Italian patients who satisfied the International Study Group criteria for BD and 235 healthy age- and sex-matched blood donors were genotyped for the -463 G/A promoter polymorphism of the MPO gene by molecular methods. The patients were subgrouped according to the presence or absence of clinical manifestations. RESULTS: The distribution of allele and genotype frequencies of the MPO -463A/G polymorphism did not differ significantly between the BD patients and the healthy controls. Carriers of the -463 A allele (A/A or A/G) [odds ratio (OR) 0.7, 95% confidence interval (CI) 0.5-1.1] and homozygosity for A allele (OR 0.3, 95% CI 0.1-1.3) were less frequent among BD patients than among the controls, but the difference was not statistically significant. No significant associations were found when BD patients with and those without clinical manifestations were compared. CONCLUSION: Our data suggest that the -463 G/A promoter polymorphism of the MPO gene is not associated with susceptibility to, and clinical expression of, BD in Italian patients. PMID- 17855425 TI - Serum keratan sulfate is a promising marker of early articular cartilage breakdown. AB - OBJECTIVES: To find serum markers that may serve as indices for an early diagnosis of degeneration or damage of the articular cartilage. METHODS: Twenty four healthy volunteers, 19 individuals with knee trauma (KT) and 31 with knee osteoarthritis (OA) were evaluated. KT patients were divided into a group (n = 5) with an injury <2 months old (recent KT) and a group (n = 14) with that >2 months old (old KT). Articular cartilage damage was assessed using either arthroscopy or direct observation. Serum concentrations of hyaluronic acid (HA), cartilage proteoglycan aggrecan turnover epitope (CS846) and cartilage oligomeric protein (COMP) were measured using enzyme-linked immunosorbent assay kits and those of keratan sulfate (KS) and chondroitin-6-sulfate (C6S) using high-performance liquid chromatography. RESULTS: Serum KS in the recent KT group (2095 +/- 594 ng/ml) was significantly higher than that in the old KT group (1373 +/- 418 ng/ml; P = 0.021), and serum COMP in the recent KT group (1572 +/- 182 ng/ml) showed a tendency that was higher than that in the old KT group (1350 +/- 250 ng/ml; P = 0.079). Serum KS in OA patients with Kellgren and Lawrence (KL) grades 0 and I (1456 +/- 334 ng/ml) showed a tendency that was higher than that in OA patients with KL grades II, III and IV (1248 +/- 220 ng/ml; P = 0.084). CONCLUSIONS: The serum concentration of KS correlated with the damage of the articular cartilage and it was significantly increased even at an early stage after the injury. PMID- 17855426 TI - The HECATE genes regulate female reproductive tract development in Arabidopsis thaliana. AB - Successful fertilization in plants requires the properly coordinated development of female reproductive tissues, including stigma, style, septum and transmitting tract. We have identified three closely related genes, HECATE1 (HEC1), HECATE2 (HEC2) and HECATE3 (HEC3), the expression domains of which encompass these regions of the Arabidopsis gynoecium. The HEC genes encode putative basic helix loop-helix (bHLH) transcription factors with overlapping functionality. Depending on the amount of HEC function missing, plants exhibit varying degrees of infertility, defects in septum, transmitting tract and stigma development and impaired pollen tube growth. The observed phenotypes are similar to those reported for mutations in the SPATULA (SPT) gene, which also encodes a bHLH transcription factor required for development of the same female tissues. We show that the HEC proteins can dimerize with SPT in a yeast two-hybrid system, indicating that the HEC genes work in concert with SPT to coordinately regulate development of the female reproductive tract. Furthermore, when the HEC genes are ectopically expressed from the CaMV 35S promoter, some of the resulting transgenic plants show pin-shaped inflorescences, suggesting that the HEC genes are probably involved in auxin-mediated control of gynoecium patterning. PMID- 17855427 TI - Collaboration between Smads and a Hox protein in target gene repression. AB - Hox proteins control the differentiation of serially iterated structures in arthropods and chordates by differentially regulating many target genes. It is yet unclear to what extent Hox target gene selection is dependent upon other regulatory factors and how these interactions might affect target gene activation or repression. We find that two Smad proteins, effectors of the Drosophila Dpp/TGF-beta pathway, that are genetically required for the activation of the spalt (sal) gene in the wing, collaborate with the Hox protein Ultrabithorax (Ubx) to directly repress sal in the haltere. The repression of sal is integrated by a cis-regulatory element (CRE) through a remarkably conserved set of Smad binding sites flanked by Ubx binding sites. If the Ubx binding sites are relocated at a distance from the Smad binding sites, the proteins no longer collaborate to repress gene expression. These results support an emerging view of Hox proteins acting in collaboration with a much more diverse set of transcription factors than has generally been appreciated. PMID- 17855428 TI - Independent functions and mechanisms for homeobox gene Barx1 in patterning mouse stomach and spleen. AB - Homeobox genes convey positional information in embryos and their role in patterning the mammalian gut is a topic of considerable interest. Barx1 is expressed selectively in fetal stomach mesenchyme and directs differentiation of overlying endoderm. Recombinant tissue cultures and study of young mouse embryos previously suggested that Barx1 controls expression of secreted Wnt antagonists, which suppress endodermal Wnt signaling, to enable stomach epithelial differentiation. We overcame mid-gestational lethality of Barx1(-/-) mouse embryos and report here the spectrum of anomalies in a distinctive and unprecedented model of gastrointestinal homeotic transformation. Using various mouse models, we confirm the importance of attenuated Wnt signaling in stomach development and the role of Barx1 in suppressing endodermal Wnt activity. Absence of Barx1 also results in fully penetrant defects in positioning and expansion of the spleen, an organ that originates within the mesothelial lining of the stomach. Barx1 is absent from the spleen primordium but highly expressed in the mesogastrium, indicating an indirect effect on spleen development. However, our results argue against a role for Wnt antagonism in genesis of the spleen. Mouse spleen development relies on several homeodomain transcriptional regulators that are expressed in the spleen primordium. Loss of Barx1 does not affect expression of any of these genes but notably reduces expression of Wt1, a transcription factor implicated in spleen morphogenesis and expressed in the mesothelium. These observations place Barx1 proximally within a Wt1 pathway of spleen development and reveal how a homeotic regulator employs different molecular mechanisms to mold neighboring organs. PMID- 17855429 TI - Polycomb group proteins function in the female gametophyte to determine seed development in plants. AB - Polycomb group (PcG) proteins are evolutionary conserved proteins that stably maintain established transcriptional patterns over cell generations. The FERTILIZATION INDEPENDENT SEED (FIS) PcG complex from plants has a similar composition to the Polycomb repressive complex 2 from animals. Mutations in FIS genes cause parent-of-origin-dependent seed abortion. Every seed inheriting a mutant fis allele from the mother is destined to abort, regardless of the presence of a wild-type paternal allele. We tested in Arabidopsis whether the parent-of-origin-dependent seed abortion caused by lack of the FIS subunit MSI1 is caused by parental imprinting of the MSI1 gene. Our data show that MSI1 is not an imprinted gene and that early paternal MSI1 expression is not sufficient to rescue msi1 mutant seeds. By contrast, expression of MSI1 in msi1 female gametophytes is necessary to restore normal seed development, strongly arguing that the female gametophytic effect of fis mutants is caused by a functional requirement for an intact FIS complex in the female gametophyte. Thus, FIS mediated expression patterns established in the female gametophyte can impact on seed development, establishing fis mutants as true female gametophytic maternal effect mutants. PMID- 17855430 TI - Cis-regulatory analysis of nodal and maternal control of dorsal-ventral axis formation by Univin, a TGF-beta related to Vg1. AB - The TGF-beta family member Nodal is essential for specification of the dorsal ventral axis of the sea urchin embryo, but the molecular factors regulating its expression are not known. Analysis of the nodal promoter is an excellent entry point to identify these factors and to dissect the regulatory logic driving dorsal-ventral axis specification. Using phylogenetic footprinting, we delineated two regulatory regions located in the 5' region of the nodal promoter and in the intron that are required for correct spatial expression and for autoregulation. The 5' regulatory region contains essential binding sites for homeodomain, bZIP, Oct, Tcf/Lef, Sox and Smad transcription factors, and a binding site for an unidentified spatial repressor possibly related to Myb. Soon after its initiation, nodal expression critically requires autoregulation by Nodal and signaling by the maternal TGF-beta Univin. We show that Univin is related to Vg1, that both Nodal and Univin signal through Alk4/5/7, and that zygotic expression of univin, like that of nodal, is dependent on SoxB1 function and Tcf/beta catenin signaling. This work shows that Tcf, SoxB1 and Univin play essential roles in the regulation of nodal expression in the sea urchin and suggests that some of the regulatory interactions controlling nodal expression predate the chordates. The data are consistent with a model of nodal regulation in which a maternal TGF-beta acts in synergy with maternal transcription factors and with spatial repressors to establish the dorsal-ventral axis of the sea urchin embryo. PMID- 17855431 TI - Fgf3 is required for dorsal patterning and morphogenesis of the inner ear epithelium. AB - The inner ear, which contains sensory organs specialized for hearing and balance, develops from an ectodermal placode that invaginates lateral to hindbrain rhombomeres (r) 5-6 to form the otic vesicle. Under the influence of signals from intra- and extraotic sources, the vesicle is molecularly patterned and undergoes morphogenesis and cell-type differentiation to acquire its distinct functional compartments. We show in mouse that Fgf3, which is expressed in the hindbrain from otic induction through endolymphatic duct outgrowth, and in the prospective neurosensory domain of the otic epithelium as morphogenesis initiates, is required for both auditory and vestibular function. We provide new morphologic data on otic dysmorphogenesis in Fgf3 mutants, which show a range of malformations similar to those of Mafb (Kreisler), Hoxa1 and Gbx2 mutants, the most common phenotype being failure of endolymphatic duct and common crus formation, accompanied by epithelial dilatation and reduced cochlear coiling. The malformations have close parallels with those seen in hearing-impaired patients. The morphologic data, together with an analysis of changes in the molecular patterning of Fgf3 mutant otic vesicles, and comparisons with other mutations affecting otic morphogenesis, allow placement of Fgf3 between hindbrain-expressed Hoxa1 and Mafb, and otic vesicle-expressed Gbx2, in the genetic cascade initiated by WNT signaling that leads to dorsal otic patterning and endolymphatic duct formation. Finally, we show that Fgf3 prevents ventral expansion of r5-6 neurectodermal Wnt3a, serving to focus inductive WNT signals on the dorsal otic vesicle and highlighting a new example of cross-talk between the two signaling systems. PMID- 17855432 TI - Induction of proepicardial marker gene expression by the liver bud. AB - Cells of the coronary vessels arise from a unique extracardiac mesothelial cell population, the proepicardium, which develops posterior to the sinoatrial region of the looping-stage heart. Although contribution of the proepicardial cells to cardiac development has been studied extensively, it remains unresolved how the proepicardium is induced and specified in the mesoderm during embryogenesis. It is known, however, that the proepicardium develops from the mesothelium that overlays the liver bud. Here, we show that the expression of proepicardial marker genes - Wt1, capsulin (epicardin, pod1, Tcf21) and Tbx18, can be induced in naive mesothelial cells by the liver bud, both in vitro and in vivo. Lateral embryonic explants, when co-cultured with the liver bud, were induced to express these proepicardial marker genes. The same induction of the marker genes was detected in vivo when a quail liver bud was implanted in the posterior-lateral regions of a chick embryo. This ectopic induction of marker gene expression was not evident when other endodermal tissues, such as the lung bud or stomach, were implanted. This inductive response to the liver bud was not detectable in host embryos before stage 12 (16-somite stage). These results suggest that, after a specific developmental stage, a large area of the mesothelium becomes competent to express proepicardial marker genes in response to localized liver-derived signal(s). The developmentally regulated competency of mesothelium and a localized inductive signal might play a role in restricting the induction of the proepicardial marker gene expression to a specific region of the mesothelium. The data might also provide a foundation for future engineering of a coronary vascular progenitor population. PMID- 17855433 TI - CXCL16 is a novel mediator of the innate immunity of epidermal keratinocytes. AB - The epidermis is constantly exposed to a variety of microbial pathogens and plays a vital role in resisting them. Soluble CXC chemokine ligand (CXCL) 16, which is one of the ELR- CXC chemokines, acts as a mediator of innate immunity by attracting CXC chemokine receptor (CXCR) 6-expressing cells, such as activated T cells and NKT cells. However, the production of CXCL16 by non-immune cells remains unclear. We found that cultured keratinocytes produced a significant amount of CXCL16 (2-3 ng per 10(6) cells per 24 h). Stimulation with tumor necrosis factor alpha, IL-1alpha, IFN-gamma, peptidoglycan and polyinosinic polycytidylic acid [poly(I:C)] enhanced CXCL16 production. The forms of CXCL16 in the culture supernatants had molecular weights of 14, 28 and 50 kDa. Immunohistochemical analysis revealed that the normal human epidermis expressed CXCL16. As several chemokines have anti-microbial activities, we studied the anti microbial activity of CXCL16. The chemokine domain of CXCL16 at concentrations >5 microg ml(-1) had significant anti-microbial activity against Staphylococcus aureus and Escherichia coli. Killing activity was retained at the physiological salt concentration in the presence of carbonate. In conclusion, CXCL16 is a novel mediator of the innate immune reactivities of epidermal keratinocytes. PMID- 17855434 TI - Conformation of MHC class II I-A(g7) is sensitive to the P9 anchor amino acid in bound peptide. AB - Type I diabetes is a chronic autoimmune disease resulting in the destruction of insulin-producing beta cells in the pancreas. In humans, disease incidence is linked to expression of specific MHC class II alleles and in mice type I diabetes is associated with the class II allele I-A(g7). I-A(g7) contains a polymorphism that is shared by human class II alleles associated with the disease, at position 57 in the beta chain, in which aspartic acid is changed to a serine. The P9 pocket in the peptide-binding groove is in part shaped by beta57, and therefore the structure of this pocket is modified in I-A(g7). Using mAbs, we have previously determined that alternative conformations of I-A(g7) form in response to peptide binding. In this study, we have extended these findings by examining how peptides induce I-A(g7) molecules to adopt different conformations. By mutating the amino acid in the P9 position of either class II-associated invariant chain peptide (CLIP) or glutamic acid decarboxylase (GAD) 65 (207-220), we have determined that the chemical nature of the P9 anchor amino acid, either acidic or small hydrophobic, affects the overall conformation of the I-A(g7) class II molecule. T cell hybridomas specific for GAD 65 (207-220) in the context of I-A(g7) were also examined for recognition of I-A(g7) bound to GAD 65 (207 220), in which Glu(217) in the P9 position was changed to alanine. We found that although some TCRs were able to recognize both peptides in the context of I A(g7), and thus both class II conformations, approximately one-third of the T cells tested were not able to recognize the alternate class II conformation formed with the mutated peptide. These results indicate that the I-A(g7) conformations may affect functional activation of T cells, and thus may play a role in autoimmunity. PMID- 17855435 TI - TAP-inhibiting proteins US6, ICP47 and UL49.5 differentially affect minor and major histocompatibility antigen-specific recognition by cytotoxic T lymphocytes. AB - CTLs specific for hematopoietic system-restricted minor histocompatibility antigens (mHags) can serve as reagents for cellular adoptive immunotherapy after allogeneic stem cell transplantation (SCT). In the HLA-mismatched setting, CTLs specific for hematopoietic system-restricted mHags expressed solely by the non self 'allo' HLA molecules could be used to treat relapse after HLA-mismatched SCT. The generation of mHag-specific allo-HLA-restricted CTLs requires antigen presenting cells (APCs) expressing low numbers of endogenous peptides to avoid co induction of undesired allo-HLA reactivities. In this study, we exploited viral evasion strategies to generate APCs expressing a controlled set of endogenous peptides. Herpesviruses persist lifelong following primary infection due to expression of viral gene products that hamper T-cell recognition of infected cells. The herpesvirus-derived proteins US6, ICP47 and UL49.5 down-regulate endogenous antigen presentation in human APCs via inhibition of the transporter associated with antigen processing. EBV-transformed B cell lines transduced with retroviral vectors encoding US6, ICP47 or UL49.5 exhibited a stable decrease in cell-surface HLA class I expression and were protected from lysis by mHag specific CTLs. Exogenous addition of mHag peptide fully restored target cell recognition. UL49.5 showed the most pronounced inhibitory effect, reducing HLA class I expression and mHag-specific lysis up to 99%. UL49.5 also significantly diminished allo-HLA reactivities mediated by allo-HLA-specific CTLs. In conclusion, UL49.5 could be a powerful new tool to study and modulate endogenous antigen presentation. PMID- 17855436 TI - Risk factors for obesity in 7-year-old European children: the Auckland Birthweight Collaborative Study. AB - OBJECTIVE: To identify risk factors associated with obesity in primary school children, with a particular focus on those which can be modified. To identify critical periods and growth patterns in the development of childhood obesity. METHODS: 871 New Zealand European children were enrolled in a longitudinal study at birth and data were collected at birth, 1, 3.5 and 7 years of age. Data collected at 7 years included weight, height, bioelectrical impedance analysis (BIA), television viewing time and a 24 h body movement record (actigraphy). The outcome measure was percentage body fat (PBF), which was calculated at 3.5 and 7 years using BIA. Univariate and multiple regression analyses were carried out using PBF as a continuous variable. RESULTS: Multivariable analysis found maternal overweight/obesity, maternal age, female gender, sedentary activity time and hours of television viewing to be independently associated with PBF at 7 years. Growth variables (birth weight, rapid weight gain in infancy, early (1-3.5 years) and middle childhood (3.5-7 years)) were also independently associated with adiposity at 7 years. There was a strong correlation between PBF at 3.5 years and PBF at 7 years. CONCLUSIONS: Many primary school aged children start on the trajectory of obesity in the preschool years, which suggests interventions need to start early. Maternal overweight/obesity, television watching, sedentary activity time and rapid weight gain in infancy, early and middle childhood are risk factors for childhood obesity, and are all potentially modifiable. PMID- 17855437 TI - Objective measurement of levels and patterns of physical activity. AB - OBJECTIVE: To measure the levels and patterns of physical activity, using accelerometers, of 11-year-old children participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). DESIGN: Cross-sectional analysis. SETTING: ALSPAC is a birth cohort study located in the former county of Avon, in the southwest of England. This study used data collected when the children were 11 years old. PARTICIPANTS: 5595 children (2662 boys, 2933 girls). The children are the offspring of women recruited to a birth cohort study during 1991-2. The median age (95% CI) of the children is now 11.8 (11.6 to 11.9) years. METHODS: Physical activity was measured over a maximum of 7 consecutive days using the MTI Actigraph accelerometer. MAIN OUTCOME MEASURES: Level and pattern of physical activity. RESULTS: The median physical activity level was 580 counts/min. Boys were more active than girls (median (IQR) 644 (528-772) counts/min vs 529 (444 638) counts/min, respectively). Only 2.5% (95% CI 2.1% to 2.9%) of children (boys 5.1% (95% CI 4.3% to 6.0%), girls 0.4% (95% CI 0.2% to 0.7%) met current internationally recognised recommendations for physical activity. Children were most active in summer and least active in winter (difference = 108 counts/min). Both the mother and partner's education level were inversely associated with activity level (p for trend <0.001 (both mother and partner)). The association was lost for mother's education (p for trend = 0.07) and attenuated for partner's education (p for trend = 0.02), after adjustment for age, sex, season, maternal age and social class. CONCLUSIONS: A large majority of children are insufficiently active, according to current recommended levels for health. PMID- 17855438 TI - Rotavirus vaccination for Hong Kong children: an economic evaluation from the Hong Kong Government perspective. AB - AIMS: To perform an economic analysis of government-funded universal rotavirus vaccination in Hong Kong from the government's perspective. METHODS: A Markov model of costs and effects (disability averted) associated with universal vaccination was compared with no vaccination. In both strategies, newborns were studied until 5 years of age or until they died, using cost, probability and utility data from the literature. The potential cost savings and cost effectiveness of vaccination were calculated and their sensitivities to changes in vaccine and health care costs, presumed decline in vaccine efficacy over time, and the use of discounting and age weights were determined. RESULTS: Depending on assumptions, the new rotavirus vaccines would be cost saving to the Hong Kong Government if they cost less than US$40-92 per course. Higher vaccine costs would quickly lead to an incremental cost-effectiveness ratio exceeding that of the gross national product per capita if the mortality rate of rotavirus gastroenteritis remained at zero. CONCLUSIONS: Based on 2002 demographic, cost and morbidity data and reasonable uncertainty estimates of these variables, a universal rotavirus vaccination programme paid for by the Hong Kong Government is cost neutral at a per course vaccine cost of US$40-92. For a fixed vaccine cost, the potential savings and cost effectiveness of the vaccine increase with higher estimated health care costs and vice versa. PMID- 17855439 TI - Infant HIV infection despite "universal" antenatal testing. AB - We reviewed the antenatal HIV testing history, clinical presentation and outcome of 25 infants diagnosed with HIV between 1 January 2001 and 31 December 2005 in a tertiary referral hospital in London. Of the 25 cases, 21 had received antenatal care in the UK. Twelve mothers had not had an antenatal HIV test, four had tested positive antenatally, while five had had a negative HIV test on antenatal booking, implying seroconversion in pregnancy. When mothers had not been diagnosed antenatally, infants presented with severe infections, which were fatal in six cases. The majority (65%) of the children have long-term neurological sequelae. HIV seroconversion is an important cause of infant HIV in the UK. PMID- 17855440 TI - Young people's experiences of managing asthma and diabetes at school. AB - PURPOSE: To examine the experiences and concerns of young people and their parents regarding the management of medication for asthma or diabetes whilst at school. METHODS: Face-to-face semi-structured interviews were conducted with 69 young people aged 8-15 years (43 with asthma and 26 with diabetes) and their parents (138 interviews in total) in their own homes. Respondents were recruited through randomly selected general practice surgeries in contrasting areas in South East England. Interviews were audio-recorded, transcribed verbatim and analysed using established qualitative analytical procedures. RESULTS: Young people with asthma and diabetes discussed difficulties regarding access to and use of their medicines at school which may jeopardise optimal condition management. School medicines policies could be a further hindrance. Young people endeavour to find ways to accommodate their medication and condition related needs whilst at school, in an attempt to limit the impact of their condition upon school activities such as sport, school trips and relationships with peers. Parents expressed concern regarding the awareness and levels of support available to their sons/daughters, in particular if a crisis should develop. DISCUSSION: In order to ensure optimal care, there is a need for the development of protocols tailored to the needs of young people with different conditions. These should preferably be devised in partnership between the young person, their parents and the school to ensure that the flexibility and support required for optimal management are offered. PMID- 17855441 TI - Differential expression of novel tyrosine kinase substrates during breast cancer development. AB - To identify novel tyrosine kinase substrates that have never been implicated in cancer, we studied the phosphoproteomic changes in the MCF10AT model of breast cancer progression using a combination of phosphotyrosyl affinity enrichment, iTRAQ technology, and LC-MS/MS. Using complementary MALDI- and ESI-based mass spectrometry, 57 unique proteins comprising tyrosine kinases, phosphatases, and other signaling proteins were detected to undergo differential phosphorylation during disease progression. Seven of these proteins (SPAG9, Toll-interacting protein (TOLLIP), WBP2, NSFL1C, SLC4A7, CYFIP1, and RPS2) were validated to be novel tyrosine kinase substrates. SPAG9, TOLLIP, WBP2, and NSFL1C were further proven to be authentic targets of epidermal growth factor signaling and Iressa (gefitinib). A closer examination revealed that the expression of SLC4A7, a bicarbonate transporter, was down-regulated in 64% of the 25 matched normal and tumor clinical samples. The expression of TOLLIP in clinical breast cancers was heterogeneous with 25% showing higher expression in tumor compared with normal tissues and 35% showing the reverse trend. Preliminary studies on SPAG9, on the other hand, did not show differential expression between normal and diseased states. This is the first time SLC4A7 and TOLLIP have been discovered as novel tyrosine kinase substrates that are also associated with human cancer development. Future molecular and functional studies will provide novel insights into the roles of TOLLIP and SLC4A7 in the molecular etiology of breast cancer. PMID- 17855442 TI - Evolution of an arsenal: structural and functional diversification of the venom system in the advanced snakes (Caenophidia). AB - Venom is a key innovation underlying the evolution of advanced snakes (Caenophidia). Despite this, very little is known about venom system structural diversification, toxin recruitment event timings, or toxin molecular evolution. A multidisciplinary approach was used to examine the diversification of the venom system and associated toxins across the full range of the approximately 100 million-year-old advanced snake clade with a particular emphasis upon families that have not secondarily evolved a front-fanged venom system ( approximately 80% of the 2500 species). Analysis of cDNA libraries revealed complex venom transcriptomes containing multiple toxin types including three finger toxins, cobra venom factor, cysteine-rich secretory protein, hyaluronidase, kallikrein, kunitz, lectin, matrix metalloprotease, phospholipase A(2), snake venom metalloprotease/a disintegrin and metalloprotease, and waprin. High levels of sequence diversity were observed, including mutations in structural and functional residues, changes in cysteine spacing, and major deletions/truncations. Morphological analysis comprising gross dissection, histology, and magnetic resonance imaging also demonstrated extensive modification of the venom system architecture in non-front-fanged snakes in contrast to the conserved structure of the venom system within the independently evolved front-fanged elapid or viperid snakes. Further, a reduction in the size and complexity of the venom system was observed in species in which constriction has been secondarily evolved as the preferred method of prey capture or dietary preference has switched from live prey to eggs or to slugs/snails. Investigation of the timing of toxin recruitment events across the entire advanced snake radiation indicates that the evolution of advanced venom systems in three front fanged lineages is associated with recruitment of new toxin types or explosive diversification of existing toxin types. These results support the role of venom as a key evolutionary innovation in the diversification of advanced snakes and identify a potential role for non-front-fanged venom toxins as a rich source for lead compounds for drug design and development. PMID- 17855443 TI - Contribution of anaphase B to chromosome separation in higher plant cells estimated by image processing. AB - Anaphase can be categorized into the two subphases of anaphase A and B, but anaphase B has not been clearly described in higher plant cells. In this study, we time-sequentially followed the dynamics of chromosome segregation and spindle elongation in tobacco BY-2 cells using histone-red fluorescent protein (RFP) and green fluorescent protein (GFP)-tubulin, respectively. Construction of kymographs and determination of the positions of chromosomes and spindle edges by image processing revealed that anaphase B contributed to about 40% of the chromosome separation in distance, which is comparable with that in animal cells. These results suggest that higher plant cells potentially possess the process of anaphase B. PMID- 17855444 TI - Background correction of personal dose distributions by a novel unfolding algorithm. AB - The dosimetry service Seibersdorf monitors more than 20,000 persons with typical monitoring period of one month. The use of thermoluminescence (TL)-dosemeters during the last 30 years allows measurements of even low dose values (some 10 muSv) with sufficient uncertainty. Consideration of the natural background contribution or transport dose which needs to be subtracted from the measured dose requires special protocols which differ significantly from country to country. The chosen protocol has not only a strong influence on the individual dose values (especially for low doses) but changes significantly the whole dose distribution function, as well as the corresponding statistical describing parameters (mean doses, median values, etc.) of these distributions. On the basis of the measured (uncorrected) distribution function the attempt was made to extract both the background doses as well as the remaining occupationally caused dose contribution. For this approach the uncorrected dose values of all customers from several years were analysed and a superposition of two independent log normal distributions was assumed. By means of a new unfolding algorithm both components were isolated and the corresponding parameters were calculated. The paper gives a detailed description of the procedure and summarises the resulting dose distributions. PMID- 17855445 TI - Implementing a hospital guideline on pneumonia: a semi-quantitative review. AB - BACKGROUND AND OBJECTIVE: To quantify the impact of different guideline implementation interventions to improve treatment of community-acquired pneumonia (CAP) in a hospital setting. METHODS: Pubmed, the Cochrane Library, the Cochrane Effective Practice and Organization of Care specialized register, EMBASE and CINAHL. STUDY SELECTION: Hospital-based trials studying the effect of guidelines on compliance with care processes, clinical and/or economic outcomes in the treatment of CAP together with a description of their implementation interventions. DATA EXTRACTION: Two independent reviewers extracted and categorized utilized implementation interventions, assessed intensity of use and calculated changes for process of care variables, clinical and economical outcomes. Correlations between interventions and improvement of outcomes were assessed by means of Spearman's rho-test and Mann-Whitney U-test. RESULTS: In 27 included studies, educational meetings (21/27) and distribution of written material (14/27) were the two most used interventions. Most individual studies show positive overall results, but taken together, no significant relation between number or type of implementation interventions and improvement of outcomes could be detected. Only audit and feedback showed a significant negative influence on the improvement rate of length of stay (p = 0.003; n = 20). CONCLUSION: Other hospital-specific factors are likely to have a higher impact on the rate of improvement than the implementation interventions alone. Describing which interventions are most successful is unlikely to be correct without taking these hospital-specific factors into account. Future research should focus on how to identify and define these factors and how to adapt the intervention to hospital-specific factors. PMID- 17855446 TI - Intrauterine growth and survival in cerebral palsy. AB - BACKGROUND AND OBJECTIVES: Deviations in birth weight from an optimum, thought to be just above average for gestational age, are known to increase both the risk of developing cerebral palsy and the risk of developing cerebral palsy of a more severe form. Influences on survival of such deviations from average birth weight for gestational age are not known. METHODS: Using a well-established, well defined and large UK cohort of children and adults with cerebral palsy, followed from birth for nearly 25 years, we investigate the influence of deviations from average birth weight for gestational age, on survival duration, after allowing for severity of impairments. RESULTS: A total of 3946 cases, born between 1980 and 1996 were included. For those born much lighter than average for gestational age, more than 30% (n = 313) had a severe motor or cognitive impairment, rising to as much as 40% (n = 239) for extremely low weights. For female infants, the proportions severely impaired increased to as much as 35% (n = 49) among those born much heavier than average; no such increase was observed for heavier than average male infants. For those with four severe impairments and a birth weight close to average for gestational age, around 60% (n = 140) survived to age 15 years, compared with less than 40% (n = 9) of those born much heavier than average for gestational age. A 2-year-old child with four severe impairments and born heavy for gestational age has a predicted median life expectancy of 79% (95% CI 70% to 88%) of the average. CONCLUSIONS: Infants with a birth weight lighter than average for gestational age have an increased likelihood of developing a more severe form of cerebral palsy. Surprisingly, among the infants who are very severely impaired, those born much lighter than average for gestational age have the longest life expectancy, and those born much heavier than average for gestational age have the shortest life expectancy. PMID- 17855447 TI - Common genetic variation in calpain-10 gene (CAPN10) and diabetes risk in a multi ethnic cohort of American postmenopausal women. AB - Calpain-10 (CAPN10) protein may play a role in glucose metabolisms, pancreatic beta-cell insulin secretion and thermogenesis. Emerging evidence has implicated a role of CAPN10 genetic variants in the risk of type 2 diabetes mellitus (T2DM). Previous association studies, however, have focussed only on several variants initially reported and provided inconsistent results. We conducted a large nested case-control study to comprehensively investigate the associations between common variations in CAPN10 gene and T2DM risk among postmenopausal women aged 50-79 years from the Women's Health Initiative Observational Study. After comprehensive screening in 244 randomly chosen control samples (n = 61 for each of four ethnic groups), we selected a total of 12 tagging single nucleotide polymorphisms (tSNPs) spanning 91 kb in CAPN10 and genotyped them in 1543 diabetes cases and 2132 matched controls (including 968 cases and 968 controls for whites, 366 and 732 for blacks, 152 and 303 for Hispanics and 98 and 195 for Asian/Pacific Islanders). There were no significant associations between any individual tSNP and T2DM, within either the full study sample or any specific ethnic group. Nor was there any evidence of association between common CAPN10 haplotypes and diabetes risk (global tests for differences in risk were P = 0.31 for overall common haplotypes, P = 0.44 for haplotypes in block 1 and P = 0.37 for haplotypes in block 2). In conclusion, we did not observe any significant associations of the common SNPs or haplotypes across the CAPN10 gene with diabetes risk in our large and ethnically diverse cohort of postmenopausal women. PMID- 17855448 TI - Mtmr13/Sbf2-deficient mice: an animal model for CMT4B2. AB - Charcot-Marie-Tooth (CMT) disease denotes a large group of genetically heterogeneous hereditary motor and sensory neuropathies and ranks among the most common inherited neurological disorders. Mutations in the Myotubularin-Related Protein-2 (MTMR2) or MTMR13/Set-Binding Factor-2 (SBF2) genes are associated with the autosomal recessive disease subtypes CMT4B1 or CMT4B2. Both forms of CMT share similar features including a demyelinating neuropathy associated with reduced nerve conduction velocity (NCV) and focally folded myelin. Consistent with a common disease mechanism, the homodimeric MTMR2 acts as a phosphoinositide D3-phosphatase with phosphatidylinositol (PtdIns) 3-phosphate and PtdIns 3,5 bisphosphate as substrates while MTMR13/SBF2 is catalytically inactive but can form a tetrameric complex with MTMR2, resulting in a strong increase of the enzymatic activity of complexed MTMR2. To prove that MTMR13/SBF2 is the disease causing gene in CMT4B2 and to provide a suitable animal model, we have generated Mtmr13/Sbf2-deficient mice. These animals reproduced myelin outfoldings and infoldings in motor and sensory peripheral nerves as the pathological hallmarks of CMT4B2, concomitant with decreased motor performance. The number and complexity of myelin misfoldings increased with age, associated with axonal degeneration, and decreased compound motor action potential amplitude. Prolonged F-wave latency indicated a mild NCV impairment. Loss of Mtmr13/Sbf2 did not affect the levels of its binding partner Mtmr2 and the Mtmr2-binding Dlg1/Sap97 in peripheral nerves. Mice deficient in Mtmr13/Sbf2 together with known Mtmr2 deficient animals will be of major value to unravel the disease mechanism in CMT4B and to elucidate the critical functions of protein complexes that are involved in phosphoinositide-controlled processes in peripheral nerves. PMID- 17855449 TI - Association of single-nucleotide polymorphisms in MTMR9 gene with obesity. AB - Genetic factors are clearly involved in the development of obesity, but the genetic background of obesity remains largely unclear. Starting from 62 663 gene based single-nucleotide polymorphisms (SNPs) in three sequential case-control association studies, we identified a replicated association between the obesity phenotype (BMI > or =30 kg/m(2)) and a SNP (rs2293855) located in the myotublarin related protein 9 (MTMR9) gene in the chromosomal segment 8p23-p22. P-values (minor allele dominant model) of the first set (93 cases versus 649 controls) and the second set (564 cases versus 562 controls) were 0.008 and 0.0002, respectively. The association was replicated in the third set [394 cases versus 958 controls, P = 0.005, odds ratio (95% CI) =1.40 (1.11-1.78)]. The global P value was 0.0000005. A multiple regression analysis revealed that gender, age BMI and rs2293855 genotype (minor allele dominant model) were significantly associated with both systolic and diastolic blood pressures. MTMR9 was shown to be the only gene within the haplotype block that contained SNPs associated with obesity. Both the transcript and protein of MTMR9 were detected in the rodent lateral hypothalamic area as well as in the arcuate nucleus, and the protein co existed with orexin, melanin concentrating hormone, neuropeptide Y and proopiomelanocortin. The levels of MTMR9 transcript in the murine hypothalamic region increased after fasting and were decreased by a high-fat diet. Our data suggested that genetic variations in MTMR9 may confer a predisposition towards obesity and hypertension through regulation of hypothalamic neuropeptides. PMID- 17855450 TI - Distal axonopathy in an alsin-deficient mouse model. AB - Mutations in Alsin are associated with chronic juvenile amyotrophic lateral sclerosis (ALS2), juvenile primary lateral sclerosis and infantile-onset ascending spastic paralysis. The primary pathology and pathogenic mechanism of the disease remain largely unknown. Here we show that alsin-deficient mice have motor impairment and degenerative pathology in the distal corticospinal tracts without apparent motor neuron pathology. Our data suggest that ALS2 is predominantly a distal axonopathy, rather than a neuronopathy in the central nervous system of the mouse model, implying that alsin plays an important role in maintaining the integrity of the corticospinal axons. PMID- 17855451 TI - Translation of SOX10 3' untranslated region causes a complex severe neurocristopathy by generation of a deleterious functional domain. AB - Peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome and Hirschsprung disease (PCWH) is a complex neurocristopathy caused by SOX10 mutations. Most PCWH-associated SOX10 mutations result in premature termination codons (PTCs), for which the molecular mechanism has recently been delineated. However, the first mutation reported to cause PCWH was a disruption of the native stop codon that by conceptual translation extends the protein into the 3' untranslated region (3'-UTR) for an additional 82 residues. In this study, we sought to determine the currently unknown molecular pathology for the SOX10 extension mutation using in vitro functional assays. Despite the wild-type SOX10 coding sequence remaining intact, the extension mutation led to severely diminished transcription and DNA-binding activities. Nevertheless, it showed no dominant-negative interference with wild-type SOX10 in vitro. Within the 82-amino acid tail, an 11-amino acid region (termed the WR domain) was responsible primarily for the deleterious properties of the extension. The WR domain, presumably forming an alpha-helix structure, inhibited SOX10 transcription activities if inserted in the carboxyl-terminal half of the protein. The WR domain can also affect other transcription factors with a graded effect when fused to the carboxyl termini, suggesting that it probably elicits a toxic functional activity. Together, molecular pathology for the SOX10 extension mutation is distinct from that of more common PTC mutations. Failure to properly terminate SOX10 translation causes the generation of a deleterious functional domain that occurs because of translation of the normal 3'-UTR; the mutant fusion protein causes a severe neurological disease. PMID- 17855452 TI - Functional characterization of NF-kappaB inhibitor-like protein 1 (NFkappaBIL1), a candidate susceptibility gene for rheumatoid arthritis. AB - Several studies have implicated the NF-kappaB inhibitor-like protein 1 (NFkBIL1) gene located in the class III region of the major histocompatibility complex (MHC) as a possible susceptibility locus for rheumatoid arthritis (RA). Based on limited homology, it has been suggested to be a member of the inhibitor of NF kappaB (IkappaB) family of proteins, but a role in mRNA processing has also been proposed. We have investigated the expression of NFkBIL1 in RA synovial tissue and characterized its function. Real-time PCR showed the two NFkBIL1 mRNA splice variants are expressed in a tissue-specific manner. Dual immunofluorescent staining of human RA synovium with polyclonal anti-NFkBIL1 antibodies and anti CD68, anti-CD3 or anti-factor VIII showed that NFkBIL1 was expressed in the rheumatoid synovial lining and sub-lining layers and co-localized in CD68+ and CD3+, but not Factor VIII+ cells. Confocal microscopy of cultured synovial fibroblasts revealed expression in speckled nuclear and homogenous cytoplasmic distributions, suggesting shuttling between the cytoplasmic and nuclear compartments. Functional tests showed that NFkBIL1 isoforms were incapable of associating with NF-kappaB and did not inhibit it, thus disproving the hypothesis that NFkBIL1 functions as an IkappaB. Affinity purification of endogenous NFkBIL1 proteins and co-immunoprecipitation experiments showed that NFkBIL1 can associate with mRNA and with three protein partners, identified by mass spectrometry as leukophysin, translation elongation factor 1 alpha and CTP synthase I. These data support a potential role for NFkBL1 in the pathogenesis of RA and indicates that it may be involved in mRNA processing or the regulation of translation. PMID- 17855453 TI - Reduced life span with heart and muscle dysfunction in Drosophila sarcoglycan mutants. AB - In humans, genetically diverse forms of muscular dystrophy are associated with a disrupted sarcoglycan complex. The sarcoglycan complex resides at the muscle plasma membrane where it associates with dystrophin. There are six known sarcoglycan proteins in mammals whereas there are only three in Drosophila melanogaster. Using imprecise P element excision, we generated three different alleles at the Drosophila delta-sarcoglycan locus. Each of these deletions encompassed progressively larger regions of the delta-sarcoglycan gene. Line 840 contained a large deletion of the delta-sarcoglycan gene, and this line displayed progressive impairment in locomotive ability, reduced heart tube function and a shortened life span. In line 840, deletion of the Drosophila delta-sarcoglycan gene produced disrupted flight muscles with shortened sarcomeres and disorganized M lines. Unlike mammalian muscle where degeneration is coupled with ongoing regeneration, no evidence for regeneration was seen in this Drosophila sarcoglycan mutant. In contrast, line 28 was characterized with a much smaller deletion that affected only a portion of the cytoplasmic region of the delta sarcoglycan protein and left intact the transmembrane and extracellular domains. Line 28 had a very mild phenotype with near normal life span, intact cardiac function and normal locomotive activity. Together, these data demonstrate the essential nature of the transmembrane and extracellular domains of Drosophila delta-sarcoglycan for normal muscle structure and function. PMID- 17855454 TI - Genetic variation in the DNA repair genes is predictive of outcome in lung cancer. AB - To assess whether DNA repair gene variants influence the clinical behaviour of lung cancer we examined the impact of a comprehensive panel of 109 non-synonymous single-nucleotide polymorphisms (nsSNPs) in 50 DNA repair genes on overall survival (OS) in 700 lung cancer patients. Fifteen nsSNPs were associated with OS, significantly greater than that expected (P = 0.04). SNPs associated with prognosis mapped primarily to two repair pathways--nucleotide excision repair (NER): ERCC5 D1104H (P = 0.004); ERCC6 G399D (P = 0.023), ERCC6 Q1413R (P = 0.025), POLE (P = 0.014) and base excision repair: APEX1 D148E (P = 0.028); EXO1 E670G (P = 0.007); POLB P242R (P = 0.018). An increasing number of variant alleles in EXO1 was associated with a poorer prognosis [hazard ratio (HR) = 1.24; P = 0.0009]. A role for variation in NER and BRCA2/FA pathway genes as determinants of OS was provided by an analysis restricted to the 456 patients treated with platinum-based agents. Our data indicate that the pathway-based approach has the potential to generate prognostic markers of clinical outcome. PMID- 17855455 TI - Homelessness and health: challenges for health psychology. AB - Homelessness can be seen as a challenge for health psychology in research and practice on several levels: analysing the risks of becoming homeless; the living conditions of being homeless and their impact on health risks and problems; homeless youth as a specific phenomenon; health problems in the context of homelessness; service utilization and barriers and effects of interventions in the context of homelessness. With these levels, a framework is outlined for the contributions to this Special Issue. In the end, homelessness is discussed as an issue for prevention in three respects for a comprehensive approach in health psychology. PMID- 17855456 TI - Predictors of homelessness among older adults in New York city: disability, economic, human and social capital and stressful events. AB - We interviewed 61 housed and 79 homeless adults aged 55 and over about disability; economic, human and social capital; and stressful life events prior to becoming homeless. Over half of the homeless group had previously led conventional lives. Human capital, social capital and life events were more important than disability or economic capital in predicting homelessness. The homeless adults were younger, more likely to be male and better educated than housed adults, but had shorter job tenure and fewer social ties. Homeless adults faced multiple, cascading risks, including job loss and housing loss. Implications for prevention are discussed. PMID- 17855457 TI - Health inequalities and homelessness: considering material, spatial and relational dimensions. AB - Homelessness is a pressing health concern involving material hardship, social marginalization and restrained relationships between homeless and housed people. This article links relational aspects of homelessness, and its health consequences, with material and spatial considerations through the use of photo elicitation interviews with 12 rough sleepers in London. We highlight the relevance of embodied deprivation for a health psychology that is responsive to the ways in which social inequalities can get under the skin of homeless people and manifest as health disparities. PMID- 17855458 TI - Health and street/ homeless youth. AB - This article reviews the Canadian literature on health issues for homeless/street youth couched in terms of the broad determinants of health. A description of the target population is presented, followed by a discussion of the health risks associated with living in marginal and precarious situations ;on the street'. In particular, the potential consequences of engaging in the risky and often dangerous activities (e.g. substance abuse and high-risk sex) associated with the street lifestyle are discussed. Key conclusions drawn from the relevant literature are taken into consideration in a final section that includes a discussion of the policy implications of this work. PMID- 17855459 TI - Idealization and neglect: health concepts of homeless adolescents. AB - How do homeless adolescents think of health and perceive their own health status? Episodic interviews with (N = 24) homeless adolescents (age 14-20 years) in Germany addressed several aspects of the adolescents' representations of health: their definitions and experiences of health and links between both. Results show the meaning of health for participants in street life. Patterns of perceiving the relevance of health and of possible influences on it reveal a tension between idealizing and neglecting health. A similar tension characterizes how the adolescents refer to their way from family to street life. Conclusions for health promotion for this target group are drawn. PMID- 17855460 TI - Just thinking about it: social capital and suicide ideation among homeless persons. AB - Suicide ideation is a sensitive indicator of personal well-being. While ideation occurs in roughly 3 percent of the US population annually, in this study rates are 10 times higher. This article explores the role of social capital in mediating negative life circumstances on ideation for a sample of 161 homeless adults in a mid-sized Southern US metropolitan area. Our results imply that social capital does not function the same way for homeless persons as it does for the general population. This finding supports growing evidence that social capital's much touted benefits for personal well-being may not apply to disadvantaged populations. PMID- 17855461 TI - Homelessness and mental health in Ghana: everyday experiences of Accra's migrant squatters. AB - This article discusses everyday experiences of transient homelessness in Ghana's capital, Accra. Episodic interviews with individuals living in squatter settlements in the wealthy East Legon suburb explored: (1) roots of homelessness; (2) everyday experiences and coping strategies; (3) relationship between experiences and (mental) health; (4) needs and interventions. Three intersecting forms of insecurity framed participants' everyday experience: financial, legal and psychosocial. Physical and psychological stresses were common; physical illnesses rare. Coping strategies facilitated adaptation but not transformation of everyday circumstances. We explore possibilities for intervention and discuss relevance of this study to the health psychology and African literatures on homelessness. PMID- 17855462 TI - Expert knowledge, cognitive polyphasia and health: a study on social representations of homelessness among professionals working in the voluntary sector in London. AB - This article develops a social representational approach to understanding expert knowledge and its relation to health. Research with homelessness professionals (HPs) working in the UK voluntary sector shows that expert definitions of homelessness can either undermine or enhance the health of the homeless. Guided by the concepts of social representations and cognitive polyphasia, the analysis reveals a contradictory field of knowledge, which reflects the struggle of professionals to sustain a humanizing approach and resist the pressures of statutory agendas. We conclude pointing to the need of recognizing the impact of professional's knowledge on the health and care policies for the homeless. PMID- 17855463 TI - Applying the Gelberg-Andersen behavioral model for vulnerable populations to health services utilization in homeless women. AB - We applied the Gelberg-Andersen Behavioral Model for Vulnerable Populations to predict health services utilization (HSU) in 875 homeless US women. Structural models assessed the impact of predisposing (demographics, psychological distress, alcohol/drug problems, homelessness severity), enabling (health insurance, source of care, barriers) and need (illness) variables on HSU (preventive care, outpatient visits, hospitalizations). Homelessness severity predicted illness, barriers and less insurance. Distress predicted more barriers, illness and less outpatient HSU. Drug problems predicted hospitalizations. Barriers predicted more illness and less outpatient HSU. Health and homelessness indicators were worse for White women. Better housing, access to care and insurance would encourage appropriate HSU. PMID- 17855464 TI - Evidence that theory of planned behaviour variables mediate the effects of socio demographic variables on homeless people's participation in service programmes. AB - This article reports findings from two studies (N = 88, N = 100) using Ajzen's theory of planned behaviour (TPB) to predict homeless people's uptake of service programmes. Study 1 was conducted with an opportunity sample whereas Study 2 employed a representative sample. Both studies provide support for the application of the TPB, and demonstrate that the effects of demographic characteristics on behaviour were mediated by TPB variables. The discussion focuses on the role of attitudinal and normative components in actual behaviour, and on the potential role of social normative processes and stigmatization in homeless people's uptake of services. PMID- 17855465 TI - Outcomes of a brief sexual health intervention for homeless youth. AB - Homeless youth face various health challenges. The effectiveness of a short intervention to promote sexual health in 572 homeless 16-23-year-olds (M = 19.467+1.89) was conducted using a quasi-experimental repeated measures design. Data collected at three time points (pre-intervention, immediately post intervention and follow-up) via laptop computers were analyzed using multivariate general linear mixed models. A significant condition by time interaction was found for self-reported AIDS/STD knowledge; intervention participants had higher scores at first post-test. Females scored significantly higher on cognitive and behavioral outcomes while males reported significantly more sexual risk-taking behaviors. Findings support gender-specific interventions. PMID- 17855466 TI - HIV risk reduction in a nurse case-managed TB and HIV intervention among homeless adults. AB - This study evaluated a six-month nurse case-managed intervention against a standard care control program among 295 sheltered homeless adults from Los Angeles, USA. The primary aim of the intervention was encouraging latent tuberculosis infection treatment completion. The secondary aim was reducing HIV risk, the focus of this report. A longitudinal path model revealed that the intervention impacted cognitive factors of AIDS Knowledge, Perceived AIDS Risk and Self-efficacy for Condom Use, but did not impact substance use and risky sexual behaviors. The dual intervention program for HIV and TB provided promising synergistic effects by targeting risk factors common to both infections. PMID- 17855467 TI - Why modest geographic effects for asthma? Pharmaceutical treatment as neutralizing mechanism. AB - Research on geographic health effects has been greatly advanced with the development of multilevel statistical techniques but less is known about the possible mechanisms by which social and geographical environments may affect physical health. In spite of well-established relationships between asthma etiology and the broader living environments, multilevel research on asthma shows at best marginal geographic effects. Based on in-depth, open-ended interviews with 50 caretakers of school-age children (6-12 years) diagnosed with asthma living in two different communities, this article elucidates mechanisms by which neighborhood effects may be neutralized. Caretakers of children with mild, controllable asthma attempt to create asthma-safe zones by administering long term control and quick-relief medication, by removing indoor environmental triggers and by avoiding dangerous environments. At home, school and outdoors, the key strategy to control asthma was the use of relatively effective and accessible medications. Children with severe asthma did not benefit as much from medications but it was unclear that different communities made a difference in asthma care. PMID- 17855468 TI - Identity ambivalence and embodiment in women's accounts of the gynaecological examination. AB - In this article we are interested in the negotiation of identities in women's narratives of their gynaecological examination and more particularly, the shifts of identity positions that permeate their stories. Taking a constructionist view of discourse and identity, we make two arguments in the article. First, we demonstrate that women talking about their gynaecological examinations constructed their selves ambiguously. The identity spaces that they discursively opened in the narratives were not inhabited. Second, we show that the embodiment of their identities--the inclusion of the body into the construction of self- fluctuates depending on the stage of the narrative of the examination. PMID- 17855469 TI - 'That's just the cesspool where they dump all the trash': exploring working class men's perceptions and experiences of social capital and health. AB - This article explores issues relating to the concept of social capital which has been become an important explanation for inequalities in health. It is based on an analysis of in-depth interviews with working class men living in two contrasting socio-economic areas--one relatively disadvantaged and one advantaged. It highlights the role of different community contexts in the nature and extent of local social capital. In particular, it demonstrates how de industrialization and economic change as well as material deprivation and a perceived dis-investment in local communities impacted on the men's levels of social capital. Analysis also shows the ways in which gender mediates the processes through which social capital is developed and accessed as a personal and social resource, and how the norms and values associated with working class masculinities appeared to preclude the men from building supportive health enhancing relationships with others in their community. The prominence of social capital has focused attention on the subjective dimensions of community life as potential determinants of health. This article has, therefore, sought to contribute to this field by widening our understanding about the relationship between social capital, gender and health. PMID- 17855470 TI - A delicate balance: negotiating renal transplantation, immunosuppression and adherence to medical regimen. AB - Despite the volume of biomedical and psychosocial discourse surrounding both renal transplantation and the immune system, there is a limit to current understandings of immunosuppression in the context of kidney transplantation. For example, we do not know how the immunosuppressed renal transplant recipient experiences and understands their immune system and body. In addition, we do not know if the patient is as fixated on ;graft survival' as their healthcare team or whether other concerns are more relevant. What is missing is the discourse of those who actually 'live' the medically altered immune system in the context of renal transplantation. We propose that this gap in knowledge is bound to an acknowledged problem among renal transplant recipients and their healthcare teams -a lack of compliance with recommended medical regimens. Our argument here is that an exploration of patient intimacy with transplant-related immunosuppression might illuminate a different understanding of this experience that could enhance health professionals' understanding and their subsequent approach to treatment. We contend that the embodied and contextual experience of the patient needs to be equally valued in order to enhance patient outcomes. PMID- 17855471 TI - A critical realist approach to understanding and evaluating heart health programmes. AB - Secondary prevention programmes for Coronary Heart Disease (CHD) aim to reduce cardiovascular risks and promote health in people with heart disease. Though programmes have been associated with health improvements in study populations, access to programmes remains low, and quality and effectiveness is highly variable. Current guidelines propose significant modifications to programmes, but existing research provides little insight into why programme effectiveness varies so much. Drawing on a critical realist approach, this article argues that current research has been based on an impoverished ontology, which has elements of positivism, does not explore the social determinants of health or the effects on outcomes of salient contextual factors, and thereby fails to account for programme variations. Alternative constructivist approaches are also weak and lacking in clinical credibility. An alternative critical realist approach is proposed that draws on the merits of subjectivist and objectivist approaches but also reflects the complex interplay between individual, programme-related, socio cultural and organizational factors that influence health outcomes in open systems. This approach embraces measurement of objective effectiveness but also examines the mechanisms, organizational and contextual-related factors causing these outcomes. Finally, a practical example of how a critical realist approach can guide research into secondary prevention programmes is provided. PMID- 17855472 TI - Stochastic segmentation models for array-based comparative genomic hybridization data analysis. AB - Array-based comparative genomic hybridization (array-CGH) is a high throughput, high resolution technique for studying the genetics of cancer. Analysis of array CGH data typically involves estimation of the underlying chromosome copy numbers from the log fluorescence ratios and segmenting the chromosome into regions with the same copy number at each location. We propose for the analysis of array-CGH data, a new stochastic segmentation model and an associated estimation procedure that has attractive statistical and computational properties. An important benefit of this Bayesian segmentation model is that it yields explicit formulas for posterior means, which can be used to estimate the signal directly without performing segmentation. Other quantities relating to the posterior distribution that are useful for providing confidence assessments of any given segmentation can also be estimated by using our method. We propose an approximation method whose computation time is linear in sequence length which makes our method practically applicable to the new higher density arrays. Simulation studies and applications to real array-CGH data illustrate the advantages of the proposed approach. PMID- 17855473 TI - ST91 [2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride]-mediated spinal antinociception and synergy with opioids persists in the absence of functional alpha-2A- or alpha-2C-adrenergic receptors. AB - Agonists acting at alpha2-adrenergic receptors (alpha2ARs) produce antinociception and synergize with opioids. The alpha2ARs are divided into three subtypes, alpha(2A)AR, alpha(2B)AR, and alpha(2C)AR. Most alpha2AR agonists require alpha(2A)AR activation to produce antinociception and opioid synergy. The same subtype also mediates the side effect of sedation, which limits the clinical utility of these compounds. Identification of a non-alpha(2A)AR-mediated antinociceptive agent would enhance the therapeutic utility of alpha2AR agonists in pain management. Previous studies have suggested that the alpha2AR agonist ST91 [2-(2,6-diethylphenylamino)-2-imidazoline hydrochloride] has a nonsedating, non-alpha(2A)AR mechanism of action. We examined the pharmacology of spinal ST91 and its interaction with the delta-opioid agonist deltorphin II (Tyr-D-Ala-Phe Glu-Val-Val-Gly amide) in mice lacking either functional alpha(2A)ARs or alpha(2C)ARs. All drugs were administered by direct lumbar puncture, and drug interactions were evaluated using isobolographic analysis. In contrast to the majority of alpha2AR agonists, ST91 potency was only moderately reduced (3-fold) in the absence of the alpha(2A)AR. Studies with the alpha2AR subtype-preferring antagonists BRL-44408 (2-[2H-(1-methyl-1,3-dihydroisoindole)methyl]-4,5 dihydroimidazole maleate) and prazosin [[4-(4-amino-6,7-dimethoxy-quinazolin-2 yl) piperazin-1-yl]-(2-furyl)methanone] and the pan-alpha2AR antagonist SKF-86466 (6-chloro-2,3,4,5-tetrahydro-3-methyl-1-H-3-benzazepine) suggest a shift from alpha(2A)AR to the other alpha2AR subtype(s) in the absence of alpha(2A)AR. Antinociceptive synergy with deltorphin II was preserved in the absence of either alpha(2A)AR or alpha(2C)AR. In conclusion, ST91 activates both alpha(2A)AR and non-alpha(2A)AR subtypes to produce spinal antinociception and opioid synergy. This study confirms that the spinal pharmacology of ST91 differs from that of other alpha2AR agonists and extends those data to include spinal synergy with opioid agonists. The unique profile of ST91 may be advantageous in pain management. PMID- 17855474 TI - An 80-amino acid deletion in the third intracellular loop of a naturally occurring human histamine H3 isoform confers pharmacological differences and constitutive activity. AB - In this article, we pharmacologically characterized two naturally occurring human histamine H3 receptor (hH3R) isoforms, hH3R(445) and hH3R(365). These abundantly expressed splice variants differ by a deletion of 80 amino acids in the intracellular loop 3. In this report, we show that the hH3R(365) is differentially expressed compared with the hH3R(445) and has a higher affinity and potency for H3R agonists and conversely a lower potency and affinity for H3R inverse agonists. Furthermore, we show a higher constitutive signaling of the hH3R(365) compared with the hH3R(445) in both guanosine-5'-O-(3-[35S]thio) triphosphate binding and cAMP assays, likely explaining the observed differences in hH3R pharmacology of the two isoforms. Because H3R ligands are beneficial in animal models of obesity, epilepsy, and cognitive diseases such as Alzheimer's disease and attention deficit hyperactivity disorder and currently entered clinical trails, these differences in H3R pharmacology of these two isoforms are of great importance for a detailed understanding of the action of H3R ligands. PMID- 17855475 TI - Neuroprotective effects of glyceryl nonivamide against microglia-like cells and 6 hydroxydopamine-induced neurotoxicity in SH-SY5Y human dopaminergic neuroblastoma cells. AB - Glyceryl nonivamide (GLNVA), a vanilloid receptor (VR) agonist, has been reported to have calcitonin gene-related peptide-associated vasodilatation and to prevent subarachnoid hemorrhage-induced cerebral vasospasm. In this study, we investigated the neuroprotective effects of GLNVA on activated microglia-like cell mediated- and proparkinsonian neurotoxin 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells. In coculture conditions, we used lipopolysaccharide (LPS)-stimulated BV-2 cells as a model of activated microglia. LPS-induced neuronal death was significantly inhibited by diphenylene iodonium (DPI), an inhibitor of NADPH oxidase. However, capsazepine, the selective VR1 antagonist, did not block the neuroprotective effects of GLNVA. GLNVA reduced LPS-activated microglia-mediated neuronal death, but it lacked protection in DPI-pretreated cultures. GLNVA also decreased LPS activated microglia induced overexpression of neuronal nitric-oxide synthase (nNOS) and glycoprotein 91 phagocyte oxidase (gp91(phox)) on SH-SY5Y cells. Pretreatment of BV-2 cells with GLNVA diminished LPS-induced nitric oxide production, overexpression of inducible nitric-oxide synthase (iNOS), and gp91(phox) and intracellular reactive oxygen species (iROS). GLNVA also reduced cyclooxygenase (COX)-2 expression, inhibitor of nuclear factor (NF)-kappaB (IkappaB)alpha/IkappaBbeta degradation, NF-kappaB activation, and the overproduction of tumor necrosis factor-alpha, interleukin (IL)-1beta, and prostaglandin E2 in BV-2 cells. However, GLNVA augmented anti-inflammatory cytokine IL-10 production on LPS-stimulated BV-2 cells. Furthermore, in 6-OHDA treated SH-SY5Y cells, GLNVA rescued the changes in condensed nuclear and apoptotic bodies, prevented the decrease in mitochondrial membrane potential, and reduced cells death. GLNVA also suppressed accumulation of iROS and up-regulated heme oxygenase-1 expression. 6-OHDA-induced overexpression of nNOS, iNOS, COX-2, and gp91(phox) was also reduced by GLNVA. In summary, the neuroprotective effects of GLNVA are mediated, at least in part, by decreasing the inflammation- and oxidative stress-associated factors induced by microglia and 6-OHDA. PMID- 17855476 TI - Subtype-selective corticotropin-releasing factor receptor agonists exert contrasting, but not opposite, effects on anxiety-related behavior in rats. AB - The corticotropin-releasing factor (CRF) system mediates stress responses. Extrahypothalamic CRF1 receptor activation has anxiogenic-like properties, but anxiety-related functions of CRF2 receptors remain unclear. The present study determined the effects of intracerebroventricular administration of a CRF2 agonist, urocortin 3, on behavior of male Wistar rats in the shock-probe, social interaction, and defensive withdrawal tests of anxiety-like behavior. Equimolar doses of stressin1-A, a novel CRF1 agonist, were administered to separate rats. The effects of pyrazolo[1,5-a]-1,3,5-triazin-4-amine,8-[4-(bromo)-2-chlorophenyl] N, N-bis(2-methoxyethyl)-2,7-dimethyl-(9Cl) (MJL-1-109-2), a CRF1 antagonist, on behavior in the shock-probe test also were studied. Stressin1-A increased anxiety like behavior in the social interaction and shock-probe tests. Stressin1-A elicited behavioral activation and defensive burying at lower doses (0.04 nmol), but it increased freezing, grooming, and mounting at 25-fold higher (1-nmol) doses. Conversely, systemic administration of MJL-1-109-2 (10 mg/kg) had anxiolytic-like effects in the shock-probe test. Unlike stressin1-A or MJL-1-109 2, i.c.v. urocortin 3 infusion did not alter anxiety-like behavior in the shock probe test across a range of doses that reduced locomotion and rearing and increased grooming. Urocortin 3 also did not decrease social interaction, but it decreased anxiety-like behavior in the defensive withdrawal test at a 2-nmol dose. Thus, i.c.v. administration of CRF1 and CRF2 agonists produced differential, but not opposite, effects on anxiety-like behavior. Urocortin 3 (i.c.v.) did not consistently decrease or increase anxiety-like behavior, the latter unlike effects seen previously after local microinjection of CRF2 agonists into the septum or raphe. With increasing CRF1 activation, however, the behavioral expression of anxiety qualitatively changes from "coping" to "noncoping" and offensive, agonistic behaviors. PMID- 17855477 TI - Long-term changes in the muscarinic M1 receptor induced by instantaneous formation of wash-resistant xanomeline-receptor complex. AB - Unlike other M1 muscarinic acetylcholine receptor agonists, xanomeline demonstrates a unique mode of binding to the receptor. It not only binds reversibly to the receptor's conventional orthosteric site but also binds persistently at a secondary binding domain(s) on the M1 receptor. This results in persistent activation of the receptor even after extensive washout, and allosteric modulation of the orthosteric site. In the current study, we investigated how the effects of very brief exposure (1 min) of intact Chinese hamster ovary cells expressing M1 receptors to xanomeline followed by washout change with time. Pretreatment with xanomeline for 1 min resulted in a concentration-dependent wash-resistant inhibition of [3H]N-methylscopolamine (NMS) binding, with a lower potency than that observed in the continuous presence of xanomeline in the binding assay medium. This effect was associated with wash resistant receptor activation. Incubation of pretreated and washed cells in control medium for 24 h transformed the monophasic xanomeline wash-resistant binding curve to one that exhibits two distinct potencies. This was the result of the appearance of a new very high-potency binding component without a change in the low-potency state. The delayed effects of persistently bound xanomeline are mainly due to reduction of the maximal binding of [3H]NMS without a change in its affinity. These treatment conditions also reversed persistent receptor activation by xanomeline. Our results imply that brief exposure to xanomeline followed by washing and prolonged waiting may result in delayed receptor desensitization accompanied by internalization or down-regulation. PMID- 17855478 TI - Pharmacogenetics of deoxycytidine kinase: identification and characterization of novel genetic variants. AB - Deoxycytidine kinase (DCK) is a rate-limiting enzyme in the activation of nucleoside analogs such as cytarabine (ara-C), gemcitabine, clofarabine, and others. The present study was undertaken to identify and to determine the functional consequences of genetic variants in DCK. We sequenced 1.5 kilobases of the DCK proximal promoter and all seven coding exons in International HapMap Project panels (n = 90 each) with European (Centre d' Etude du Polymorphisme Humain; CEPH) or African (Yoruba people in Ibadan, Nigeria; YRI) ancestry. Sixty four genetic polymorphisms, including three nonsynonymous coding changes (I24V, A119G, and P122S) were identified. Compared with DCK-wild-type (WT) protein, the activity of the recombinant DCK24Val, DCK119Gly, and DCK122Ser proteins was 85 +/ 5, 66 +/- 3, and 43 +/- 4%, respectively. DCK119Gly and DCK122Ser mutants had lower Km (p < 0.01) and Vmax (p < 0.001) compared with DCK-WT protein. Lymphoblast cell lines from subjects heterozygous for the coding changes had significantly lower DCK activity compared with homozygous WT subjects. Ethnic differences were observed, with African ancestry subjects demonstrating significantly higher DCK mRNA expression compared with subjects with European ancestry. In both CEPH and YRI subjects, the C allele of a 3'-untranslated region single-nucleotide polymorphism (SNP) (35708 C>T) was significantly associated with lower DCK mRNA expression. This SNP was strongly linked with other intronic SNPs, forming a major haplotype block in both ethnic groups. In an exploratory analysis, the 35708C allele was also associated with lower blast ara-C-5' triphosphate (ara-CTP) levels in acute myeloid leukemia patients receiving ara-C as continuous infusion. These results suggest that genetic variation in DCK influences its activity and expression and may predict the variability observed in intracellular levels of the ara-C active metabolite ara-CTP. PMID- 17855479 TI - P2 purinoceptor-mediated cardioprotection in ischemic-reperfused mouse heart. AB - P2 purinoceptor modulation of injury during ischemia-reperfusion was studied in murine hearts. Effects of P2 agonism or antagonism, and interstitial accumulation of P2 agonists (UTP, ATP, and ADP), were assessed in Langendorff perfused hearts during 20 min of ischemia and 45 min of reperfusion. In control hearts, ventricular pressure development recovered to 68 +/- 4 mm Hg (63 +/- 3% baseline), diastolic pressure remained elevated (23 +/- 2 mm Hg), and 26 +/- 4 U/g lactate dehydrogenase (LDH) was released during reperfusion, evidencing necrosis. Treatment with 250 nM UTP improved pressure development (85 +/- 5 mm Hg, or 77 +/- 2%) and reduced diastolic contracture (by approximately 70%, to 7 +/- 1 mm Hg) and LDH loss (by approximately 60%, to 11 +/- 2 U/g). In contrast, P2Y1 agonism with 50 nM 2-methyl-thio-ATP (2-MeSATP) was ineffective. In the presence of the P2Y antagonist suramin (10 or 200 microM), UTP no longer improved postischemic outcomes. Ischemia also substantially elevated interstitial [UTP], [ATP], and [ADP], potentially activating P2 receptors. This was supported in part by effects of antagonists: 200 microM suramin worsened LDH efflux (53 +/- 9 IU/g) and contractile dysfunction (41 +/- 2 mm Hg diastolic pressure; 28 +/- 3 mm Hg developed pressure), as did P2Y antagonism with either 10 or 100 microM reactive blue 2. However, a 10 microM concentration of suramin failed to alter outcome. P2X antagonism with 10 microM pyridoxal phosphate-6-azo-(benzene-2,4-disulfonic acid and P2X1-selective pyridoxal-alpha5-phosphate-6-phenylazo-4'-carboxylic acid (MRS2159) (30 microM) was ineffective. Data collectively support cardioprotection with low concentrations of UTP, and they are consistent with P2Y2 involvement. Endogenous nucleotides may also play a protective role, as evidenced by effects of P2 antagonists, although this warrants further investigation. PMID- 17855480 TI - Lack of effect of extracellular adenosine generation and signaling on renal erythropoietin secretion during hypoxia. AB - Previous studies have yielded conflicting results as to whether extracellular adenosine generation and signaling contributes to hypoxia-induced increases in renal erythropoietin (EPO) secretion. In this study, we combined pharmacological and genetic approaches to elucidate a potential contribution of extracellular adenosine to renal EPO release in mice. To stimulate EPO secretion, we used murine carbon monoxide exposure (400 and 750 parts per million CO, 4 h), ambient hypoxia (8% oxygen, 4 h), or arterial hemodilution. Because the ecto-5 nucleotidase (CD73, conversion of AMP to adenosine) is considered the pacemaker of extracellular adenosine generation, we first tested the effect of blocking extracellular adenosine generation with the specific CD73-inhibitor adenosine 5' (alpha,beta-methylene) diphosphate (APCP) or by gene-targeted deletion of cd73. These studies showed that neither APCP-treatment nor targeted deletion of cd73 resulted in changes of stimulated EPO mRNA or serum levels, although the increases of adenosine levels in the kidney following CO exposure were attenuated in mice with APCP treatment or in cd73(-/-) mice. Moreover, pharmacological studies using specific inhibitors of individual adenosine receptors (A1 AR, DPCPX; A 2A AR, DMPX; A 2B AR, PSB 1115; A3AR, MRS 1191) showed no effect on stimulated increases of EPO mRNA or serum levels. Finally, stimulated EPO secretion was not attenuated in gene-targeted mice lacking A1A(-/-, A2A AR-/-, A2BAR(-/-), or A3AR-/-. Together, these studies combine genetic and pharmacological in vivo evidence that increases of EPO secretion during limited oxygen availability are not affected by extracellular adenosine generation or signaling. PMID- 17855481 TI - Functional cross talk between ENaC and pendrin. PMID- 17855482 TI - Critical roles of Sp1 in gene expression of human and rat H+/organic cation antiporter MATE1. AB - A H+/organic cation antiporter (multidrug and toxin extrusion 1: MATE1/SLC47A1) plays important roles in the tubular secretion of various clinically important cationic drugs such as cimetidine. We have recently found that the regulation of this transporter greatly affects the pharmacokinetic properties of cationic drugs in vivo. No information is available about the regulatory mechanisms for the MATE1 gene. In the present study, therefore, we examined the gene regulation of human (h) and rat (r) MATE1, focusing on basal expression. A deletion analysis suggested that the regions spanning -65/-25 and -146/-38 were essential for the basal transcriptional activity of the hMATE1 and rMATE1 promoter, respectively, and that both regions contained putative Sp1-binding sites. Functional involvement of Sp1 was confirmed by Sp1 overexpression, a mutational analysis of Sp1-binding sites, mithramycin A treatment, and an electrophoretic mobility shift assay. Furthermore, we found a single nucleotide polymorphism (SNP) in the promoter region of hMATE1 (G-32A), which belongs to a Sp1-binding site. The allelic frequency of this rSNP was 3.7%, and Sp1-binding and promoter activity were significantly decreased. This is the first study to clarify the transcriptional mechanisms of the MATE1 gene and to identify a SNP affecting the promoter activity of hMATE1. PMID- 17855483 TI - Fractional urinary excretion of endothelin-1 is reduced by acute ETB receptor blockade. AB - Evidence suggests that urinary excretion of endothelin-1 (ET-1) reflects renal ET 1 production and is independent of systemic ET-1 activity. The influence of ET receptors on urinary ET-1 excretion has not been studied in humans, yet peritubular ETB receptors are abundant within the kidney. We have studied the effects of acute ETA and ETB receptor blockade with BQ-123 and BQ-788, respectively, on urinary ET-1 excretion in a randomized, placebo-controlled, double-blind study in 16 subjects with a wide range of GFRs (15-152 ml/min). Plasma ET-1 concentrations (pET-1) and urinary ET-1 excretion rate (uET-1) at baseline correlated inversely with GFR (R2 = 0.18 and 0.36, respectively, P < 0.01). However, changes in pET-1 after ET receptor antagonism were not related to changes in uET-1 (R2 = 0.007, P = 0.18). pET-1 increased only after BQ-788, alone or in combination with BQ-123, consistent with ETB receptor-mediated clearance of ET-1 from the circulation. uET-1 was reduced only after BQ-788 alone [-4.7 pg/min (SD 5.5), P < 0.01]. Because BQ-788 also reduced GFR, fractional excretion of ET 1 (FeET-1) was calculated. FeET-1 fell after BQ-788 alone [-41% (SD 26%), P < 0.01] or in combination with BQ-123 [-40% (SD 29%), P < 0.01]. FeET-1 was not altered by placebo or BQ-123 alone. In conclusion, urinary ET-1 excretion does not appear to relate to the pool of plasma ET-1. Because of the short duration of this study, it is unlikely that ET receptor blockade had significant effects on renal ET-1 production. Therefore, the reduction in FeET-1 after ETB blockade appears to indicate that renal excretion of ET-1 is at least partly facilitated by ETB receptor activation. PMID- 17855484 TI - Implications of phytoestrogen intake for breast cancer. AB - Phytoestrogens are a group of plant-derived substances that are structurally or functionally similar to estradiol. Interest in phytoestrogens has been fueled by epidemiologic data that suggest a decreased risk of breast cancer in women from countries with high phytoestrogen consumption. Women with a history of breast cancer may seek out these "natural" hormones in the belief that they are safe or perhaps even protective against recurrence. Interpretation of research studies regarding phytoestrogen intake and breast cancer risk is hampered by differences in dietary measurement, lack of standardization of supplemental sources, differences in metabolism amongst individuals, and the retrospective nature of much of the research in this area. Data regarding the role of phytoestrogens in breast cancer prevention is conflicting, but suggest early exposure in childhood or early adolescence may be protective. In several placebo-controlled randomized trials among breast cancer survivors, soy has not been found to decrease menopausal symptoms. There is very little human data on the role of phytoestrogens in preventing breast cancer recurrence, but the few studies conducted do not support a protective role. There is in vivo animal data suggesting the phytoestrogen genistein may interfere with the inhibitive effects of tamoxifen on breast cancer cell growth. PMID- 17855485 TI - Patient-reported outcomes in cancer: a review of recent research and policy initiatives. AB - There is growing recognition that patient-reported outcome (PRO) measures- encompassing, for example, health-related quality of life--can complement traditional biomedical outcome measures (eg, survival, disease-free survival) in conveying important information for cancer care decision making. This paper provides an integrated review and interpretation of how PROs have been defined, measured, and used in a range of recent cancer research and policy initiatives. We focus, in turn, on the role of PRO measurement in the evaluation and approval of cancer therapies, the assessment of cancer care in the community, patient provider decision making in clinical oncology practice, and population surveillance of cancer patients and survivors. The paper concludes with a discussion of future challenges and opportunities in PRO measure development and application, given the advancing state of the science in cancer outcomes measurement and the evolving needs of cancer decision makers at all levels. PMID- 17855486 TI - Multiple myeloma: charging toward a bright future. AB - Multiple myeloma (MM) is an incurable clonal B-cell malignancy with terminally differentiated plasma cells. It afflicts approximately 55,000 people in the United States. Over the past 5 years, significant progress has been made in the diagnosis and assessment of patients with MM. Significant advances include a simplified staging system, which has replaced the more cumbersome Durie-Salmon staging system; an updated uniform international response criteria; the development of a sensitive new serum test to detect free light chain production (free light chain assay); the recognition of specific adverse cytogenetic abnormalities; and the evolution of genomics, which will identify specific and targeted therapies for individual MM patients. For the first time in decades, major therapeutic advances have been implemented in the treatment of MM patients. These include 2 new classes of agent: immunomodulatory drugs and proteosome inhibitors. In addition, clinical trials have solidified the role of hematopoietic stem cell transplant and established the benefits of post transplant maintenance therapy. Finally, a number of new agents are in development that specifically target the myeloma cells and/or the bone marrow microenvironment. These advances have resulted in expanded treatment options, prolonged disease control and survival, and improved quality of life for patients with MM. PMID- 17855487 TI - Biological and demographic causes of high HIV and sexually transmitted disease prevalence in men who have sex with men. AB - OBJECTIVES: HIV disproportionately affects men who have sex with men (MSM). MSM and heterosexual networks are distinguished by biologically determined sexual role segregation among heterosexual individuals but not MSM, and anal/vaginal transmissibility differences. To identify how much these biological and demographic differences could explain persistent disparities in HIV/sexually transmitted disease prevalence in the United States, even were MSM and heterosexual individuals to report identical numbers of unprotected sexual partnerships per year. METHODS: A compartmental model parameterized using two population-based surveys. Role composition was varied between MSM and heterosexual subjects (insertive-only and receptive-only versus versatile individuals) and infectivity values. RESULTS: The absence of sexual role segregation in MSM and the differential anal/vaginal transmission probabilities led to considerable disparities in equilibrium prevalence. The US heterosexual population would only experience an epidemic comparable to MSM if the mean partner number of heterosexual individuals was increased several fold over that observed in population-based studies of either group. In order for MSM to eliminate the HIV epidemic, they would need to develop rates of unprotected sex lower than those currently exhibited by heterosexual individuals in the United States. In this model, for US heterosexual individuals to have a self-sustaining epidemic, they would need to adopt levels of unprotected sex higher than those currently exhibited by US MSM. CONCLUSIONS: The persistence of disparities in HIV between heterosexual individuals and MSM in the United States cannot be explained solely by differences in risky sexual behavior between these two populations. PMID- 17855488 TI - Is new variant Chlamydia trachomatis present in England and Wales? AB - BACKGROUND: A new variant C trachomatis (nvCT) strain has been recently isolated in Sweden, which has a 377 bp deletion in a portion of the plasmid that is the target area for some C trachomatis nucleic acid amplification tests (NAATs). Consequently, these platforms generate false negative results when presented with this strain. OBJECTIVE: To determine if nvCT is present in England and Wales. METHODS: Specimens which had been determined to be C trachomatis positive using an unaffected platform were tested for the presence of the deletion using an in house nested PCR assay which generated a 253 bp fragment in new variant strains and a 630 bp fragment in wild-type strains. The specimens tested could be divided into two main groups: (a) 933 specimens sourced from patients attending both genitourinary medicine services and the National Chlamydia Screening Programme were forwarded from eight key laboratories within England and Wales; (b) 179 specimens were sourced from men who have sex with men and forwarded from 30 clinics throughout the UK. RESULTS: A total of 1112 specimens were screened for the presence of the 377 bp deletion. An in-house PCR method showed that 1066 were wild-type strains. Forty-six strains failed to generate an amplicon and were therefore untypable. This is consistent with differences in the analytical sensitivity of different NAATs and probably reflective of low C trachomatis DNA load. No nvCT strains were identified. CONCLUSION: Currently, there is no evidence that nvCT is present in England and Wales. However, screening and prevalence studies are continuing and UK clinicians and microbiologists should remain vigilant for suspicious, negative results. PMID- 17855489 TI - Herpes simplex virus type 2 infection among young uncircumcised men in Kisumu, Kenya. AB - OBJECTIVES: To identify factors associated with herpes simplex virus type 2 (HSV 2) infection among men aged 18-24 in Kisumu, Kenya. METHODS: Baseline data from a randomised trial of male circumcision were analysed. Participants were interviewed for sociodemographic and behavioural risks. The outcome was HSV-2 by antibody status. Risk factors were considered singly and in combination through logistic regression models. RESULTS: Among 2771 uncircumcised men, 766 (27.6%; 95% confidence interval (CI) 26.0% to 29.3%) tested antibody positive for HSV-2. The median age at first sex was 16 years, and the median number of lifetime sexual partners was four. HSV-2 seroprevalence increased from 19% among 18-year olds to 43% among 24-year-olds (p<0.001). In multivariable analysis, statistically significant risks for infection were increasing age (adjusted odds ratio (AOR) = 1.22-2.58), being married or having a live-in female partner (AOR = 1.80; 95% CI 1.28 to 2.53), preferring "dry" sex (AOR = 1.39; 95% CI 1.14 to 1.69), reported penile cuts or abrasions during sex (AOR = 1.58; 95% CI 1.32 to 1.91), increasing lifetime sex partners (multiple response categories; AORs ranging from 1.65 to 1.97), and non-student occupation (multiple response categories; AORs ranging from 1.44 to 1.93). Risk decreased with reported condom used at last sex (AOR = 0.82; 95% CI 0.68 to 0.99). CONCLUSION: Primary prevention efforts should be initiated at an early age. The same behavioural interventions used currently for HIV prevention-abstinence, reducing the number of sex partners and increasing condom use-should be effective for HSV-2 prevention. PMID- 17855490 TI - Increased expression of cyclooxygenase 2 contributes to aberrant renin production in connexin 40-deficient kidneys. AB - We previously found that deletion of connexin 40 (Cx40) causes a misdirection of renin-expressing cells from the media layer of afferent arterioles to the perivascular tissue, extraglomerular mesangium, and periglomerular and peritubular interstitium. The mechanisms underlying this aberrant renin expression are unknown. Here, we questioned the relevance of cyclooxygenase-2 (COX-2) activity for aberrant renin expression in Cx40-deficient kidneys. We found that COX-2 mRNA levels were increased three-fold in the renal cortex of Cx40-deficient kidneys relative to wild-type (wt) kidneys. In wt kidneys, COX-2 immunoreactivity was minimally detected in the juxtaglomerular region, but renin expression was frequently associated with COX-2 immunoreactivity in Cx40 deficient kidneys. Treatment with COX-2 inhibitors for 1 wk lowered renin mRNA levels in wt kidneys by about 40%. In Cx40-deficient kidneys, basal renin mRNA levels were increased two-fold relative to wt kidneys, and these elevated mRNA levels were reduced to levels of untreated wt mice by COX-2 inhibitors. In parallel, renin immunoreactive areas were clearly reduced by COX-2 inhibitors such that renin expression vanished and decreased significantly in the periglomerular and peritubular extensions. Notably, COX-2 inhibitor treatment lowered plasma renin concentration (PRC) in wt kidneys by about 40% but did not affect the highly elevated PRC levels in Cx40-deficient mice. These findings suggest that aberrant renin-producing cells in Cx40-deficient kidneys express significant amounts of COX-2, which contribute to renin expression in these cells, in particular, those in the periglomerular and peritubular position. Apparently, these disseminated cells do not contribute to the enhanced renin secretion rates of Cx40-deficient kidneys. PMID- 17855491 TI - Social stress and recovery: implications for body weight and body composition. AB - Social stress resulting from dominant-subordinate relationships is associated with body weight loss and altered body composition in subordinate (SUB) male rats. Here, we extend these findings to determine whether stress-induced changes in energy homeostasis persist when the social stress is removed, and the animal is allowed to recover. We examined body weight (BW), body composition, and relevant endocrine measures after one or two cycles of 14 days of social stress, each followed by 21 days of recovery in each rat's individual home cage. SUB lost significantly more BW during social housing in a visible burrow system (VBS) compared with dominant (DOM) animals. Weight loss during social stress was attributable to a decrease in adipose tissue in DOM and SUB, with an additional loss of lean tissue in SUB. During both 21-day recovery periods, DOM and SUB regained lost BW, but only SUB were hyperphagic. Following recovery, SUB had a relatively larger increase in adipose tissue and plasma leptin compared with DOM, indicating that body composition changes were dependent on social status. Control animals that were weight matched to SUB or male rats exposed to the VBS environment without females, and that did not form a social hierarchy, did not exhibit changes in body composition like SUB in the VBS. Therefore, chronic social stress causes social status-dependent changes in BW, composition and endocrine measures that persist after repeated stress and recovery cycles and that may ultimately lead to metabolic disorders and obesity. PMID- 17855492 TI - Adaptive redistribution of NBCe1-A and NBCe1-B in rat kidney proximal tubule and striated ducts of salivary glands during acid-base disturbances. AB - The cellular distribution of the NH2-terminal electrogenic Na+-HCO3(-) cotransporter (NBCe1) variants NBCe1-A and NBCe1-B has been investigated in rat kidney and submandibular gland (SMG) under physiological conditions and after systemic acid-base perturbations. Moreover, the in vivo data were complemented in vitro by using an immortalized cell line derived from the S1 segment of the proximal tubule (PT) of normotensive Wistar-Kyoto rats (WKPT-0293 Cl.2). NBCe1-A was basolaterally localized in PT cells, whereas NBCe1-B exhibited intracellular and basolateral distribution. SMG showed transcript and protein expression for NBCe1-A and NBCe1-B. NBCe1-B was basolaterally localized in duct cells; NBCe1-A was found intracellularly in salivary striated ducts and apically in main duct cells. Acute metabolic acidosis significantly increased cells that showed basolateral NBCe1-A in the PT, indicating increased HCO3(-) reabsorption, and significantly decreased cells that exhibited basolateral NBCe1-B in the salivary ducts, suggesting decreased HCO3(-) secretion. Chronic acidosis had no effect on NBCe1 distribution in PT but significantly increased the percentage of cells with basolateral NBCe1-A in salivary striated duct cells, suggesting increased HCO3(-) reabsorption. In contrast, chronic alkalosis caused adaptive redistribution of NBCe1-A and NBCe1-B in renal PT, favoring decreased HCO3(-) reabsorption. In vitro, WKPT-0293 Cl.2 cells expressed key acid-base transporters. Extracellular alkalosis downregulated NBCe1-A protein. WKPT-0293 Cl.2 cells are therefore a useful model to study renal acid-base regulation in vitro. The results propose redistribution of the transporters as a potential posttranslational regulation modus during acid-base disturbances. Moreover, the data demonstrate that renal PT and salivary duct epithelia respond to acid-base disturbances by an opposite redistribution pattern for NBCe1-A and NBCe1-B, reflecting specialized functions as the HCO3(-)-reabsorbing and HCO3(-)-secreting epithelium, respectively. PMID- 17855493 TI - Thyroid status affects 5-HT2A receptor modulation of breathing before, during, and following exposure of hamsters to acute intermittent hypoxia. AB - The BIO 14.6 hamster (dystrophic), animal model of limb girdle muscular dystrophy, exhibits low plasma triiodothyronine levels, muscle weakness, and decreased breathing. After exposure to acute intermittent bouts of hypoxia, dystrophic hamsters depress ventilation relative to baseline resulting in ventilatory long-term depression (LTD). Control hamsters may increase ventilation relative to baseline resulting in ventilatory long-term facilitation (LTF). Serotonin (5-HT) receptors, especially the 5-HT(2A) subtype, are involved in the development of LTF. The purpose of this study was to evaluate the role of 5 HT(2A) receptors in ventilatory and metabolic responses before, during, and following intermittent hypoxia in eleven euthyroid, nine dystrophic, and eleven propylthiouracil (PTU)-induced hypothyroid male hamsters. Animals received subcutaneous injections of vehicle or 0.5 mg/kg MDL (5-HT(2A) receptor antagonist). Plethysmography was used to evaluate ventilatory responses of the three groups to air, five bouts of 5 min of 10% oxygen, each interspersed with 5 min of air, followed by 60 min of exposure to air. CO(2) production was measured using the flow-through method. Vehicle-treated dystrophic and PTU-treated hamsters exhibited LTD. MDL decreased body temperature in all groups. After MDL treatment, the euthyroid group exhibited LTD. MDL treatment in the dystrophic, but not in the PTU-treated hamsters, maintained tidal volume, but did not reverse LTD. CO(2) production was increased in the euthyroid group with MDL treatment. Thus, 5-HT(2A) receptors affect body temperature, ventilation, and metabolism in hamsters. The differential responses noted in this study may be in part dependent on thyroid hormone status. PMID- 17855494 TI - Oxidative stress response and gene expression with acute copper exposure in zebrafish (Danio rerio). AB - In fish, environmental pollution is one factor that induces oxidative stress, and this can disturb the natural antioxidant defense system. Oxidative stress has been well characterized in vitro, yet the in vivo effects of metal-induced oxidative stress have not been extensively studied. In two experiments we examined the impacts of copper (Cu) on gene expression, oxidative damage, and cell oxidative capacity in liver and gill of zebrafish. In the first experiment, soft water-acclimated zebrafish were exposed to 8 and 15 mug/l Cu for 48 h. This exposure resulted in significant increases in gene expression of cytochrome c oxidase subunit 17 (COX-17) and catalase, associated with both increased Cu load and protein carbonyl concentrations in the gill and liver after 48 h. In addition, we examined the potential protective effects of increased waterborne Ca(2+) (3.3 mM) and Na(+) (10 mM) on acute Cu toxicity. While both treatments were effective at reducing liver and/or gill Cu loads and attenuating oxidative damage at 48 h, 10 mM Na(+) was more protective than 3.3 mM Ca(2+). There were variable changes in the maximal activities of COX and citrate synthase (CS), indicating possible alterations in cell oxidative capacity. Moreover, Cu affected COX-to-CS ratios in both gill and liver, suggesting that Cu alters normal mitochondrial biogenic processes, possibly though metallochaperones like COX-17. Overall, this study provides important steps in determining the transcriptional and physiological endpoints of acute Cu toxicity in a model tropical species. PMID- 17855495 TI - HIF-1alpha in endurance training: suppression of oxidative metabolism. AB - During endurance training, exercising skeletal muscle experiences severe and repetitive oxygen stress. The primary transcriptional response factor for acclimation to hypoxic stress is hypoxia-inducible factor-1alpha (HIF-1alpha), which upregulates glycolysis and angiogenesis in response to low levels of tissue oxygenation. To examine the role of HIF-1alpha in endurance training, we have created mice specifically lacking skeletal muscle HIF-1alpha and subjected them to an endurance training protocol. We found that only wild-type mice improve their oxidative capacity, as measured by the respiratory exchange ratio; surprisingly, we found that HIF-1alpha null mice have already upregulated this parameter without training. Furthermore, untrained HIF-1alpha null mice have an increased capillary to fiber ratio and elevated oxidative enzyme activities. These changes correlate with constitutively activated AMP-activated protein kinase in the HIF-1alpha null muscles. Additionally, HIF-1alpha null muscles have decreased expression of pyruvate dehydrogenase kinase I, a HIF-1alpha target that inhibits oxidative metabolism. These data demonstrate that removal of HIF-1alpha causes an adaptive response in skeletal muscle akin to endurance training and provides evidence for the suppression of mitochondrial biogenesis by HIF-1alpha in normal tissue. PMID- 17855496 TI - Pharmacological actions of the peptide hormone amylin in the long-term regulation of food intake, food preference, and body weight. AB - The ability of amylin to reduce acute food intake in rodents is well established. Longer-term administration in rats (up to 24 days) shows a concomitant reduction in body weight, suggesting energy intake plays a significant role in mediating amylin-induced weight loss. The current set of experiments further explores the long-term effects of amylin (4-11 wk) on food preference, energy expenditure, and body weight and composition. Furthermore, we describe the acute effect of amylin on locomotor activity and kaolin consumption to test for possible nonhomeostatic mechanisms that could affect food intake. Four-week subcutaneous amylin infusion of high-fat fed rats (3-300 microg.kg(-1).day(-1)) dose dependently reduced food intake and body weight gain (ED(50) for body weight gain = 16.5 microg.kg( 1).day(-1)). The effect of amylin on body weight gain was durable for up to 11 wks and was associated with a specific loss of fat mass and increased metabolic rate. The body weight of rats withdrawn from amylin (100 microg.kg(-1).day(-1)) after 4 wks of infusion returned to control levels 2 wks after treatment cessation, but did not rebound above control levels. When self-selecting calories from a low- or high-fat diet during 11 wks of infusion, amylin-treated rats (300 microg.kg(-1).day(-1)) consistently chose a larger percentage of calories from the low-fat diet vs. controls. Amylin acutely had no effect on locomotor activity or kaolin consumption at doses that decreased food intake. These results demonstrate pharmacological actions of amylin in long-term body weight regulation in part through appetitive-related mechanisms and possibly via changes in food preference and energy expenditure. PMID- 17855497 TI - Baroreceptor reflex modulation by circulating angiotensin II is mediated by AT1 receptors in the nucleus tractus solitarius. AB - Circulating ANG II modulates the baroreceptor reflex control of heart rate (HR), at least partly via activation of ANG II type 1 (AT1) receptors on neurons in the area postrema. In this study, we tested the hypothesis that the effects of circulating ANG II on the baroreflex also depend on AT1 receptors within the nucleus tractus solitarius (NTS). In confirmation of previous studies in other species, increases in arterial pressure induced by intravenous infusion of ANG II had little effect on HR in urethane-anesthetized rats, in contrast to the marked bradycardia evoked by equipressor infusion of phenylephrine. In the presence of a continuous background infusion of ANG II, the baroreflex control of HR was shifted to higher levels of HR but had little effect on the baroreflex control of renal sympathetic activity. The modulatory effects of circulating ANG II on the cardiac baroreflex were significantly reduced by microinjection of candesartan, an AT1 receptor antagonist, into the area postrema and virtually abolished by microinjections of candesartan into the medial NTS. After acute ablation of the area postrema, a background infusion of ANG II still caused an upward shift of the cardiac baroreflex curve, which was reversed by subsequent microinjection of candesartan into the medial NTS. The results indicate that AT1 receptors in the medial NTS play a critical role in modulation of the cardiac baroreflex by circulating ANG II via mechanisms that are at least partly independent of AT1 receptors in the area postrema. PMID- 17855498 TI - Transport of a fluorescent cAMP analog in teleost proximal tubules. AB - Previous studies have shown that killifish (Fundulus heteroclitus) renal proximal tubules express a luminal membrane transporter that is functionally and immunologically analogous to the mammalian multidrug resistance-associated protein isoform 2 (Mrp2, ABCC2). Here we used confocal microscopy to investigate in killifish tubules the transport of a fluorescent cAMP analog (fluo-cAMP), a putative substrate for Mrp2 and Mrp4 (ABCC4). Steady-state luminal accumulation of fluo-cAMP was concentrative, specific, and metabolism-dependent, but not reduced by high K+ medium or ouabain. Transport was not affected by p aminohippurate (organic anion transporter inhibitor) or p-glycoprotein inhibitor (PSC833), but cell-to-lumen transport was reduced in a concentration-dependent manner by Mrp inhibitor MK571, leukotriene C4 (LTC4), azidothymidine (AZT), cAMP, and adefovir; the latter two compounds are Mrp4 substrates. Although MK571 and LTC4 reduced transport of the Mrp2 substrate fluorescein-methotrexate (FL-MTX), neither cAMP, adefovir, nor AZT affected FL-MTX transport. Fluo-cAMP transport was not reduced when tubules were exposed to endothelin-1, Na nitroprusside (an nitric oxide generator) or phorbol ester (PKC activator), all of which signal substantial reductions in cell-to-lumen FL-MTX transport. Fluo-cAMP transport was reduced by forskolin, and this reduction was blocked by the PKA inhibitor H-89. Finally, in membrane vesicles from Spodoptera frugiperda (Sf9) cells containing human MRP4, ATP-dependent and specific uptake of fluo-cAMP could be demonstrated. Thus, based on inhibitor specificity and regulatory signaling, cell-to-lumen transport of fluo-cAMP in killifish renal tubules is mediated by a transporter distinct from Mrp2, presumably a teleost form of Mrp4. PMID- 17855499 TI - Disease-modifying capability of murine Flt3-ligand DCs in experimental autoimmune encephalomyelitis. AB - Dendritic cells (DCs) bridge the innate and adaptive immune response, are uniquely capable of priming naive T cells, and play a critical role in the initiation and regulation of autoimmune and immune-mediated disease. At present, in vivo expansion of DC populations is accomplished primarily through the administration of the recombinant human growth factor fms-like tyrosine kinase 3 ligand (hFL), and in vitro DCs are generated using cytokine cocktails containing GM-CSF +/- IL-4. Although hFL has traditionally been used in mice, differences in amino acid sequence and biological activity exist between murine FL (mFL) and hFL, and resultant DC populations differ in phenotype and immunoregulatory functional capabilities. This study developed and characterized mFL-generated DCs and determined the therapeutic capability of mFL DCs in the autoimmune disease experimental autoimmune encephalomyelitis (EAE). Our findings demonstrate that mFL and hFL expand splenic DCs equally in vivo but that mFL-expanded, splenic DCs more closely resemble normal, resting, splenic DCs. In addition, a novel method for generating mFL-derived bone marrow-derived DCs (BM-DCs) was developed, and comparison of mFL with hFL BM-DCs found mFL BM-DCs to be less mature (i.e., lower MHC Class II, CD80, and CD86) than hFL BM-DCs. These immature mFL DCs up regulated costimulatory molecules in response to maturation stimuli LPS and TNF alpha. Mature mFL BM-DCs were immunogenic and exacerbated the clinical disease course of EAE. PMID- 17855500 TI - Transcriptional profiling of human monocytes reveals complex changes in the expression pattern of inflammation-related genes in response to the annexin A1 derived peptide Ac1-25. AB - Annexin A1 is a glucocorticoid-regulated, anti-inflammatory protein, which plays an important role as an endogenous regulator of the inflammatory response. Many of these anti-inflammatory properties are retained in the N-terminal annexin A1 peptide Ac1-25, which is released from the full-length protein by a neutrophil elastase. To elucidate whether the anti-inflammatory activity of the bioactive peptide is solely a result of immediate post-translational effects, which include the shedding of L-selectin or also involve transcriptional changes affecting leukocyte function, we recorded global gene expression changes in human monocytes stimulated with exogenously applied Ac1-25. Applying stringent selection criteria, we show that approximately 100 genes are up-regulated, and approximately 230 are down-regulated by a factor of at least two in the Ac1-25 treated monocytes. It is important that the profiling reveals that Ac1-25 induces an anti-inflammatory phenotype by down-regulating proinflammatory and up regulating anti-inflammatory mediators. These effects, elicited by exogenously applied Ac1-25, depend, to different extents, on ERK1/2 and p38 signaling pathways. This identifies the annexin A1 N-terminal peptide as a stimulus, eliciting not only short-term, post-translational effects in human monocytes but also transcriptional changes, defining a more anti-inflammatory profile. PMID- 17855501 TI - Modulation of dendritic cell differentiation by colony-stimulating factor-1: role of phosphatidylinositol 3'-kinase and delayed caspase activation. AB - Monocytes acquire a dendritic cell (DC) phenotype when cultured with GM-CSF and IL-4. By contrast, CSF-1 is a potent inducer of monocyte-to-macrophage differentiation. Increasing evidence indicates that DC development is impaired in conditions characterized by CSF-1 overproduction, including pregnancy, trauma, and diverse malignancies. To study this, we have exposed newly established monocyte-derived DC cultures to conditions of CSF-1 excess. As a consequence, differentiation is skewed toward a unique intermediate phenotype, which we have termed DC-M. Such cells exhibit macrophage-like morphology with impaired allostimulatory capacity, altered cytokine production, and a distinctive cell surface immunophenotype. In light of the emerging role of caspase activation during macrophage differentiation, the activity of caspases 3, 8, and 9 was examined in DC and DC-M cultures. It is striking that DC-M cultures exhibit a delayed and progressive increase in activation of all three caspases, associated with depolarization of mitochondrial membrane potential. Furthermore, when DC-M cultures were supplemented with an inhibitor of caspase 8 or caspase 9, impairment of DC differentiation by CSF-1 was counteracted. To investigate upstream regulators of caspase activation in DC-M cultures, experiments were performed using inhibitors of proximal CSF-1 receptor signaling. These studies demonstrated that the PI-3K inhibitors, wortmannin and LY294002, antagonize the ability of CSF-1 to inhibit DC differentiation and to promote caspase activation. Together, these data identify a novel, PI-3K-dependent pathway by which CSF-1 directs delayed caspase activation in monocytes and thereby modulates DC differentiation. PMID- 17855502 TI - IL-4 promotes the formation of multinucleated giant cells from macrophage precursors by a STAT6-dependent, homotypic mechanism: contribution of E-cadherin. AB - Multinucleated giant cells (MNG) are central players in the inflammatory response to foreign materials and in adverse responses to implants. IL-4 promotes the formation of MNG from bone marrow-derived precursors in vitro and participates in the development of the foreign body reaction in vivo. Therefore, we investigated the mechanism by which IL-4 promotes formation of MNG and engulfment of foreign bodies. We found that generation of MNG cells by IL-4 was dependent on cell density and expression of STAT6; macrophages derived from STAT6(-/-) mice were unable to form MNG in response to IL-4. No soluble factors including CCL2 or supernatants from IL-4-treated macrophages compensated for the lack of MNG cells in STAT6(-/-) cultures. We found that IL-4 must remain present during the full differentiation process and that STAT6(+/+) macrophage precursors retained their ability to differentiate into MNG over time. These MNG were able to internalize large particles efficiently, and the mononuclear STAT6(-/-) macrophages were unable to do so. Furthermore, we found that IL-4 induced expression of E-cadherin and dendritic cell-specific transmembrane protein in a STAT6-dependent manner. E cadherin expression was critical for the formation of MNG cells by IL-4; an anti E-cadherin antibody prevented the formation of large MNG. In addition, we found that STAT6(-/-) progenitors failed to fuse with STAT6(+/+), revealing the need for a homotypic interaction. Thus, IL-4 promotes the formation of MNG in a STAT6 dependent manner by regulating cell surface expression of E-cadherin, leading to homotypic cell fusion and the incorporation of large foreign bodies. PMID- 17855503 TI - Time-to-pregnancy among male greenhouse workers. AB - OBJECTIVES: Fertility problems are an increasing public health issue in industrialised countries. Exposure to exogenous agents with endocrine disrupting properties, such as some pesticides, are potential risk factors for subfertility. The aim of this study was to determine whether time-to-pregnancy (TTP) is prolonged in male greenhouse workers exposed to pesticides in comparison with a non-exposed reference group. METHODS: Data were collected through self administrated questionnaires with detailed questions on TTP, as well as on lifestyle (for example, smoking habits, coffee and alcohol consumption), work tasks, and occupational exposures of the men and their partners in the six months before conception of the most recent pregnancy. TTP was compared between male greenhouse workers (n = 694) and a non-exposed reference group (n = 613) by means of discrete proportional hazards regression analysis. RESULTS: The crude analyses did not show a decreased overall fecundability among greenhouse workers compared to the non-exposed reference group. However, when fecundability was assessed for primigravidous couples, duogravidous couples, and multigravidous couples separately, greenhouse workers were found to be less fecund when trying to conceive their first pregnancy (FR = 0.65; 95% CI 0.46 to 0.92), which is also the most valid analysis in which pregnancy planning issues were avoided. Among couples who already experienced one or more pregnancies, no association was seen between pesticide exposure and TTP after adjustment for confounders. CONCLUSION: A prolonged time-to-pregnancy was observed in male greenhouse workers exposed to pesticides before conception of their first pregnancy. PMID- 17855504 TI - Circulating lipopolysaccharides in the blood from "bioprotein" production workers. AB - BACKGROUND: Workers producing bacterial single-cell protein (BSCP), "bioprotein," are exposed to organic dust containing high levels of endoxins (lipopolysaccharides, LPS). Workers in this industry have complained of episodes of fever, fatigue, chest tightness, skin dryness and rubor. The aim of the present study was to quantify LPS and inflammatory mediators in plasma among the workers and non-exposed control subjects. METHODS: We included eight non-smoking production workers, aged 32-51 (median 38), and eight non-smoking, non-exposed controls, aged 30-51 (median 39). Airborne and plasma endotoxin concentrations were measured, as well as plasma hsCRP and different cytokines, chemokines and metalloproteinases. RESULTS: The workers who did not use personal respiratory protection were exposed to varying airborne levels of endotoxin, 430 (75-15 000) EU/m3 (median, range). The level of plasma LPS was significantly elevated (p = 0.01) among the workers compared to the non-exposed controls. The workers also had elevated levels of MCP-1 (p = 0.02), MIP-1alpha (p = 0.05) and MMP-3 (p = 0.04). IL-6 and hsCRP were also elevated among the exposed group, but not significantly (p = 0.10 and p = 0.07, respectively). CONCLUSIONS: In this study, we detected LPS in plasma of individuals exposed to high levels of LPS at their workplace. This finding is supported by elevated levels of several inflammatory cytokines among the workers, significantly exceeding that of the non-exposed control group. To the best of our knowledge, this is the first time that plasma LPS, together with increased inflammatory markers in plasma, has been detected in an occupational setting. PMID- 17855505 TI - Analysis of de novo Golgi complex formation after enzyme-based inactivation. AB - The Golgi complex is characterized by its unique morphology of closely apposed flattened cisternae that persists despite the large quantity of lipids and proteins that transit bidirectionally. Whether such a structure is maintained through endoplasmic reticulum (ER)-based recycling and auto-organization or whether it depends on a permanent Golgi structure is strongly debated. To further study Golgi maintenance in interphase cells, we developed a method allowing for a drug-free inactivation of Golgi dynamics and function in living cells. After Golgi inactivation, a new Golgi-like structure, containing only certain Golgi markers and newly synthesized cargoes, was produced. However, this structure did not acquire a normal Golgi architecture and was unable to ensure a normal trafficking activity. This suggests an integrative model for Golgi maintenance in interphase where the ER is able to autonomously produce Golgi-like structures that need pre-existing Golgi complexes to be organized as morphologically normal and active Golgi elements. PMID- 17855506 TI - Tristetraprolin inhibits Ras-dependent tumor vascularization by inducing vascular endothelial growth factor mRNA degradation. AB - Vascular endothelial growth factor (VEGF) is one of the most important regulators of physiological and pathological angiogenesis. Constitutive activation of the extracellular signal-regulated kinase (ERK) pathway and overexpression of VEGF are common denominators of tumors from different origins. We have established a new link between these two fundamental observations converging on VEGF mRNA stability. In this complex phenomenon, tristetraprolin (TTP), an adenylate and uridylate-rich element-associated protein that binds to VEGF mRNA 3'-untranslated region, plays a key role by inducing VEGF mRNA degradation, thus maintaining basal VEGF mRNA amounts in normal cells. ERKs activation results in the accumulation of TTP mRNA. However, ERKs reduce the VEGF mRNA-destabilizing effect of TTP, leading to an increase in VEGF expression that favors the angiogenic switch. Moreover, TTP decreases RasVal12-dependent VEGF expression and development of vascularized tumors in nude mice. As a consequence, TTP might represent a novel antiangiogenic and antitumor agent acting through its destabilizing activity on VEGF mRNA. Determination of TTP and ERKs status would provide useful information for the evaluation of the angiogenic potential in human tumors. PMID- 17855507 TI - Src-mediated phosphorylation of Hsp90 in response to vascular endothelial growth factor (VEGF) is required for VEGF receptor-2 signaling to endothelial NO synthase. AB - Nitric oxide (NO) release from endothelial cells, via endothelial NO synthase (eNOS) activation, is central to the proangiogenic actions of vascular endothelial growth factor (VEGF). VEGF signaling to eNOS is principally mediated by an Akt-dependent phosphorylation of eNOS and by increased association of eNOS to the molecular chaperone, heat-shock protein 90 kDa (Hsp90). Herein, we report that VEGFR-2 activation induces tyrosine phosphorylation of VEGF receptor 2 (VEGFR-2)-associated Hsp90beta. Tyrosine phosphorylation of Hsp90beta in response to VEGF is dependent on internalization of the VEGFR-2 and on Src kinase activation. Furthermore, we demonstrate that c-Src directly phosphorylates Hsp90 on tyrosine 300 residue and that this event is essential for VEGF-stimulated eNOS association to Hsp90 and thus NO release from endothelial cells. Our work identifies Y300 phosphorylation of Hsp90 as a novel regulated posttranslational modification of the chaperone and demonstrates its importance in the proangiogenic actions of VEGF, namely by regulating NO release from endothelial cells. PMID- 17855508 TI - Direct repression of cyclin D1 by SIP1 attenuates cell cycle progression in cells undergoing an epithelial mesenchymal transition. AB - Zinc finger transcription factors of the Snail/Slug and ZEB-1/SIP1 families control epithelial-mesenchymal transitions in development in cancer. Here, we studied SIP1-regulated mesenchymal conversion of epidermoid A431 cells. We found that concomitant with inducing invasive phenotype, SIP1 inhibited expression of cyclin D1 and induced hypophosphorylation of the Rb tumor suppressor protein. Repression of cyclin D1 was caused by direct binding of SIP1 to three sequence elements in the cyclin D1 gene promoter. By expressing exogenous cyclin D1 in A431/SIP1 cells and using RNA interference, we demonstrated that the repression of cyclin D1 gene by SIP1 was necessary and sufficient for Rb hypophosphorylation and accumulation of cells in G1 phase. A431 cells expressing SIP1 along with exogenous cyclin D1 were highly invasive, indicating that SIP1-regulated invasion is independent of attenuation of G1/S progression. However, in another epithelial mesenchymal transition model, gradual mesenchymal conversion of A431 cells induced by a dominant negative mutant of E-cadherin produced no effect on the cell cycle. We suggest that impaired G1/S phase progression is a general feature of cells that have undergone EMT induced by transcription factors of the Snail/Slug and ZEB-1/SIP1 families. PMID- 17855509 TI - Amphiphysin 1 is important for actin polymerization during phagocytosis. AB - Amphiphysin 1 is involved in clathrin-mediated endocytosis. In this study, we demonstrate that amphiphysin 1 is essential for cellular phagocytosis and that it is critical for actin polymerization. Phagocytosis in Sertoli cells was induced by stimulating phosphatidylserine receptors. This stimulation led to the formation of actin-rich structures, including ruffles, phagocytic cups, and phagosomes, all of which showed an accumulation of amphiphysin 1. Knocking out amphiphysin 1 by RNA interference in the cells resulted in the reduction of ruffle formation, actin polymerization, and phagocytosis. Phagocytosis was also drastically decreased in amph 1 (-/-) Sertoli cells. In addition, phosphatidylinositol-4,5-bisphosphate-induced actin polymerization was decreased in the knockout testis cytosol. The addition of recombinant amphiphysin 1 to the cytosol restored the polymerization process. Ruffle formation in small interfering RNA-treated cells was recovered by the expression of constitutively active Rac1, suggesting that amphiphysin 1 functions upstream of the protein. These findings support that amphiphysin 1 is important in the regulation of actin dynamics and that it is required for phagocytosis. PMID- 17855510 TI - Roles for Drosophila melanogaster myosin IB in maintenance of enterocyte brush border structure and resistance to the bacterial pathogen Pseudomonas entomophila. AB - Drosophila myosin IB (Myo1B) is one of two class I myosins in the Drosophila genome. In the larval and adult midgut enterocyte, Myo1B is present within the microvillus (MV) of the apical brush border (BB) where it forms lateral tethers between the MV membrane and underlying actin filament core. Expression of green fluorescent protein-Myo1B tail domain in the larval gut showed that the tail domain is sufficient for localization of Myo1B to the BB. A Myo1B deletion mutation exhibited normal larval gut physiology with respect to food uptake, clearance, and pH regulation. However, there is a threefold increase in terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive enterocyte nuclei in the Myo1B mutant. Ultrastructural analysis of mutant midgut revealed many perturbations in the BB, including membrane tethering defects, MV vesiculation, and membrane shedding. The apical localization of both singed (fascin) and Dmoesin is impaired. BBs isolated from mutant and control midgut revealed that the loss of Myo1B causes the BB membrane and underlying cytoskeleton to become destabilized. Myo1B mutant larvae also exhibit enhanced sensitivity to oral infection by the bacterial pathogen Pseudomonas entomophila, and severe cytoskeletal defects are observed in the BB of proximal midgut epithelial cells soon after infection. Resistance to P. entomophila infection is restored in Myo1B mutant larvae expressing a Myo1B transgene. These results indicate that Myo1B may play a role in the local midgut response pathway of the Imd innate immune response to Gram-negative bacterial infection. PMID- 17855511 TI - Dual actin-bundling and protein kinase C-binding activities of fascin regulate carcinoma cell migration downstream of Rac and contribute to metastasis. AB - Recurrence of carcinomas due to cells that migrate away from the primary tumor is a major problem in cancer treatment. Immunohistochemical analyses of human carcinomas have consistently correlated up-regulation of the actin-bundling protein fascin with a clinically aggressive phenotype and poor prognosis. To understand the functional and mechanistic contributions of fascin, we undertook inducible short hairpin RNA (shRNA) knockdown of fascin in human colon carcinoma cells derived from an aggressive primary tumor. Fascin-depletion led to decreased numbers of filopodia and altered morphology of cell protrusions, decreased Rac dependent migration on laminin, decreased turnover of focal adhesions, and, in vivo, decreased xenograft tumor development and metastasis. cDNA rescue of fascin shRNA-knockdown cells with wild-type green fluorescent protein-fascin or fascins mutated at the protein kinase C (PKC) phosphorylation site revealed that both the actin-bundling and active PKC-binding activities of fascin are required for the organization of filopodial protrusions, Rac-dependent migration, and tumor metastasis. Thus, fascin contributes to carcinoma migration and metastasis through dual pathways that impact on multiple subcellular structures needed for cell migration. PMID- 17855512 TI - Adenine nucleotide (ADP/ATP) translocase 3 participates in the tumor necrosis factor induced apoptosis of MCF-7 cells. AB - Mitochondrial adenine nucleotide translocase (ANT) is believed to be a component or a regulatory component of the mitochondrial permeability transition pore (mtPTP), which controls mitochondrial permeability transition during apoptosis. However, the role of ANT in apoptosis is still uncertain, because hepatocytes isolated from ANT knockout and wild-type mice are equally sensitive to TNF- and Fas-induced apoptosis. In a screen for genes required for tumor necrosis factor alpha (TNF-alpha)-induced apoptosis in MCF-7 human breast cancer cells using retrovirus insertion-mediated random mutagenesis, we discovered that the ANT3 gene is involved in TNF-alpha-induced cell death in MCF-7 cells. We further found that ANT3 is selectively required for TNF- and oxidative stress-induced cell death in MCF-7 cells, but it is dispensable for cell death induced by several other inducers. This data supplements previous data obtained from ANT knockout studies, indicating that ANT is involved in some apoptotic processes. We found that the resistance to TNF-alpha-induced apoptosis observed in ANT3 mutant (ANT3(mut)) cells is associated with a deficiency in the regulation of the mitochondrial membrane potential and cytochrome c release. It is not related to intracellular ATP levels or survival pathways, supporting a previous model in which ANT regulates mtPTP. Our study provides genetic evidence supporting a role of ANT in apoptosis and suggests that the involvement of ANT in cell death is cell type- and stimulus-dependent. PMID- 17855513 TI - Deletion in open reading frame 49 of varicella-zoster virus reduces virus growth in human malignant melanoma cells but not in human embryonic fibroblasts. AB - The ORF49 gene product (ORF49p) of the varicella-zoster virus (VZV) is likely a myristylated tegument protein, and its homologs are conserved across the herpesvirus subfamilies. The UL11 gene of herpes simplex virus type 1 and of pseudorabies virus and the UL99 gene of human cytomegalovirus are the homologs of ORF49 and have been well characterized by using mutant viruses; however, little research on the VZV ORF49 gene has been reported. Here we report on VZV ORF49p expression, subcellular localization, and effect on viral spread in vitro. ORF49p was expressed during the late phase of infection and located in the juxtanuclear region of the cytoplasm, where it colocalized mainly with the trans-Golgi network associated protein. ORF49p was incorporated into virions and showed a molecular mass of 13 kDa in VZV-infected cells and virions. To elucidate the role of the ORF49 gene, we constructed a mutant virus that lacked a functional ORF49. No differences in plaque size or cell-cell spread were observed in human embryonic fibroblast cells, MRC-5 cells, infected with the wild-type or the mutant virus. However, the mutant virus showed diminished cell-cell infection in a human malignant melanoma cell line, MeWo cells. Therefore, VZV ORF49p is important for virus growth in MeWo cells, but not in MRC-5 cells. VZV may use different mechanisms for virus growth in MeWo and MRC-5 cells. If so, understanding the role of ORF49p should help elucidate how VZV accomplishes cell-cell infections in different cell types. PMID- 17855514 TI - Dynamic interactions of the UL16 tegument protein with the capsid of herpes simplex virus. AB - The UL16 tegument protein of herpes simplex virus is conserved throughout the herpesvirus family. It has been reported to be capsid associated and may be involved in budding by providing an interaction with the membrane-bound UL11 protein. UL16 has been shown to be present in all the major locations that capsids are found (i.e., the nucleus, cytoplasm, and virions), but whether it is actually capsid associated in each of these has not been reported. Therefore, capsids were purified from each compartment, and it was found that UL16 was present on cytoplasmic but not nuclear capsids. In extracellular virions, the majority of UL16 (87%) was once again not capsid associated, which suggests that the interaction is transient during egress. Because herpes simplex virus (HSV) buds into the acidic compartment of the trans-Golgi network (TGN), the effect of pH on the interaction was examined. The amount of capsid-associated UL16 dramatically increased when extracellular virions were exposed to mildly acidic medium (pH 5.0 to 5.5), and this association was fully reversible. After budding into the TGN, capsid and tegument proteins also encounter an oxidizing environment, which is conducive to disulfide bond formation. UL16 contains 20 cysteines, including five that are conserved within a putative zinc finger. Any free cysteines that are involved in the capsid interaction or release mechanism of UL16 would be expected to be modified by N-ethylmaleimide, and, consistent with this, the amount of capsid-associated UL16 dramatically increased when virions were incubated with this compound. Taken together, these data suggest a transient interaction between UL16 and capsids, possibly modified in the acidic compartment of secretory vesicles and requiring a release mechanism that involves cysteines. PMID- 17855515 TI - Lipid raft disruption by cholesterol depletion enhances influenza A virus budding from MDCK cells. AB - Lipid rafts play critical roles in many aspects of the influenza A virus life cycle. Cholesterol is a critical structural component of lipid rafts, and depletion of cholesterol leads to disorganization of lipid raft microdomains. In this study, we have investigated the effect of cholesterol depletion by methyl beta-cyclodextrin (MbetaCD) treatment on influenza virus budding. When virus infected Madin-Darby canine kidney cells were treated with MbetaCD at the late phase of infection for a short duration, budding of virus particles, as determined by protein analysis and electron microscopy, increased with increasing concentrations and lengths of treatment. However, infectious virus yield varied, depending on the concentration and duration of MbetaCD treatment. Low concentrations of MbetaCD increased infectious virus yield throughout the treatment period, but higher concentrations caused an initial increase of infectious virus titer followed by a decrease with a longer duration. Relative infectivity of the released virus particles, on the other hand, decreased with increasing concentrations and durations of MbetaCD treatment. Loss of infectivity of virus particles is due to multiple effects of MbetaCD-mediated cholesterol depletion causing disruption of lipid rafts, changes in structural integrity of the viral membrane, leakage of viral proteins, a nick or hole on the viral envelope, and disruption of the virus structure. Exogenous cholesterol increased lipid raft integrity, inhibited particle release, and partially restored the infectivity of the released virus particles. These data show that disruption of lipid rafts by cholesterol depletion caused an enhancement of virus particle release from infected cells and a decrease in the infectivity of virus particles. PMID- 17855516 TI - p53 and hTERT determine sensitivity to viral apoptosis. AB - Apoptosis is a potent host defense against microbes. Most viruses have adapted strategies to counteract this response. Herpes simplex virus (HSV) produces a balance between pro- and antiapoptotic processes during infection. When antiapoptotic signals become limiting, infected cells die through HSV-dependent apoptosis (HDAP). Oncogenic pathways were previously implicated in HDAP susceptibility. Here, we exploited our ability to selectively express all, one, or no oncogenes in the well-defined HeLa cell system to dissect the requirements for HDAP. Human papillomavirus E6 and E7 oncogene expression was inhibited by the E2 viral repressor. Sole expression of E6 mediated HDAP sensitization. Next, two known cellular targets of E6 were independently modulated. This demonstrated that E6 sensitizes HeLa cells to HDAP through hTERT and p53. Given the universality of the apoptotic antiviral response, p53 and telomerase regulation will likely be important for counteracting host defenses in many other viral infections. PMID- 17855517 TI - Severe depletion of CD4+ CD25+ regulatory T cells from the intestinal lamina propria but not peripheral blood or lymph nodes during acute simian immunodeficiency virus infection. AB - CD4+ CD25+ regulatory T cells (Tregs) suppress the activation and proliferation of effector lymphocytes. In human immunodeficiency virus type 1 (HIV-1) infection, Tregs play a significant role in controlling the apoptotic loss of uninfected CD4+ T cells resulting from high levels of generalized immune activation. During acute HIV-1 infection, more than 50% of CD4+ T cells are depleted from the gastrointestinal lamina propria. To elucidate the role of Tregs in HIV-1-induced depletion of CD4+ T cells in the gut-associated lymphoid tissue (GALT), we first determine the distribution of Tregs in a setting of acute infection using the simian immunodeficiency virus (SIV)/pigtailed macaque model of HIV-1 disease. CD4+ T cells from the GALT, lymph nodes, and peripheral blood were isolated from SIV-infected pigtailed macaques on days 4, 14, and 114 postinoculation. Quantitative real-time reverse transcription-PCR was used to quantitate FOXP3 copy numbers in SIV-infected and uninfected control macaques. Expression of FOXP3 in the ileal lamina propria was significantly decreased at all stages of infection compared to levels in uninfected control macaques. In addition, functional analysis of ileal CD4+ T cells from SIV-infected macaques revealed a lack of suppressive activity suggestive of the absence of Tregs in that compartment. These results indicate that Tregs are rapidly depleted in the GALT of SIV-infected macaques, defining a role for the loss of Treg-mediated suppression in early events in the pathogenesis of the disease. PMID- 17855518 TI - Virally delivered cytokines alter the immune response to future lung infections. AB - Respiratory syncytial virus (RSV) is an important cause of infant morbidity and mortality worldwide and is increasingly recognized to have a role in the development and exacerbation of chronic lung diseases. There is no effective vaccine, and we reasoned that it might be possible to skew the immune system towards beneficial nonpathogenic responses by selectively priming protective T cell subsets. We therefore tested recombinant RSV (rRSV) candidates expressing prototypic murine Th1 (gamma interferon [IFN-gamma]) or Th2 (interleukin-4 [IL 4]) cytokines, with detailed monitoring of responses to subsequent infections with RSV or (as a control) influenza A virus. Although priming with either recombinant vector reduced viral load during RSV challenge, enhanced weight loss and enhanced pulmonary influx of RSV-specific CD8+ T cells were observed after challenge in mice primed with rRSV/IFN-gamma. By contrast, rRSV/IL-4-primed mice were protected against weight loss during secondary challenge but showed airway eosinophilia. When rRSV/IL-4-primed mice were challenged with influenza virus, weight loss was attenuated but was again accompanied by marked airway eosinophilia. Thus, immunization directed toward enhancement of Th1 responses reduces viral load but is not necessarily protective against disease. Counter to expectation, Th2-biased responses were more beneficial but also influenced the pathological effects of heterologous viral challenge. PMID- 17855519 TI - Localization and membrane topology of coronavirus nonstructural protein 4: involvement of the early secretory pathway in replication. AB - The coronavirus nonstructural proteins (nsp's) derived from the replicase polyproteins collectively constitute the viral replication complexes, which are anchored to double-membrane vesicles. Little is known about the biogenesis of these complexes, the membrane anchoring of which is probably mediated by nsp3, nsp4, and nsp6, as they contain several putative transmembrane domains. As a first step to getting more insight into the formation of the coronavirus replication complex, the membrane topology, processing, and subcellular localization of nsp4 of the mouse hepatitis virus (MHV) and severe acute respiratory syndrome-associated coronavirus (SARS-CoV) were elucidated in this study. Both nsp4 proteins became N glycosylated, while their amino and carboxy termini were localized to the cytoplasm. These observations imply nsp4 to assemble in the membrane as a tetraspanning transmembrane protein with a Nendo/Cendo topology. The amino terminus of SARS-CoV nsp4, but not that of MHV nsp4, was shown to be (partially) processed by signal peptidase. nsp4 localized to the endoplasmic reticulum (ER) when expressed alone but was recruited to the replication complexes in infected cells. nsp4 present in these complexes did not colocalize with markers of the ER or Golgi apparatus, while the susceptibility of its sugars to endoglycosidase H indicated that the protein had also not traveled trough the latter compartment. The important role of the early secretory pathway in formation of the replication complexes was also demonstrated by the inhibition of coronaviral replication when the ER export machinery was blocked by use of the kinase inhibitor H89 or by expression of a mutant, Sar1[H79G]. PMID- 17855520 TI - Morphogenesis of a highly replicative EGFPVP22 recombinant Marek's disease virus in cell culture. AB - Marek's disease virus (MDV) is an alphaherpesvirus for which infection is strictly cell associated in permissive cell culture systems. In contrast to most other alphaherpesviruses, no comprehensive ultrastructural study has been published to date describing the different stages of MDV morphogenesis. To circumvent problems linked to nonsynchronized infection and low infectivity titers, we generated a recombinant MDV expressing an enhanced green fluorescent protein fused to VP22, a major tegument protein that is not implicated in virion morphogenesis. Growth of this recombinant virus in cell culture was decreased threefold compared to that of the parental Bac20 virus, but this mutant was still highly replicative. The recombinant virus allowed us to select infected cells by cell-sorting cytometry at late stages of infection for subsequent transmission electron microscopy analysis. Under these conditions, all of the stages of assembly and virion morphogenesis could be observed except extracellular enveloped virions, even at the cell surface. We observed 10-fold fewer naked cytoplasmic capsids than nuclear capsids, and intracellular enveloped virions were very rare. The partial envelopment of capsids in the cytoplasm supports the hypothesis of the acquisition of the final envelope in this cellular compartment. We demonstrate for the first time that, compared to other alphaherpesviruses, MDV seems deficient in three crucial steps of viral morphogenesis, i.e., release from the nucleus, secondary envelopment, and the exocytosis process. The discrepancy between the efficiency with which this MDV mutant spreads in cell culture and the relatively inefficient process of its envelopment and virion release raises the question of the MDV cell-to-cell spreading mechanism. PMID- 17855521 TI - DDX3 DEAD-box RNA helicase is required for hepatitis C virus RNA replication. AB - DDX3, a DEAD-box RNA helicase, binds to the hepatitis C virus (HCV) core protein. However, the role(s) of DDX3 in HCV replication is still not understood. Here we demonstrate that the accumulation of both genome-length HCV RNA (HCV-O, genotype 1b) and its replicon RNA were significantly suppressed in HuH-7-derived cells expressing short hairpin RNA targeted to DDX3 by lentivirus vector transduction. As well, RNA replication of JFH1 (genotype 2a) and release of the core into the culture supernatants were suppressed in DDX3 knockdown cells after inoculation of the cell culture-generated HCVcc. Thus, DDX3 is required for HCV RNA replication. PMID- 17855522 TI - Infection of cardiomyocytes and induction of left ventricle dysfunction by neurovirulent polytropic murine retrovirus. AB - Viral infections of the heart are a causative factor of myocarditis as well as of sudden, unexpected deaths of children, yet the mechanisms of pathogenesis remain unclear, in part due to the relatively few animal models of virus-induced myocarditis. In the current study, we examined the ability of polytropic murine retroviruses to infect the heart and induce cardiac dysfunction. In situ hybridization and immunohistochemistry analysis detected virus-infected cardiomyocytes and macrophages in the heart. A significant decrease in left ventricle function, as measured by fractional shortening, was detected in mice infected with the neurovirulent retrovirus Fr98 but not in mice infected with the nonneurovirulent retrovirus Fr54. Virus infection was not associated with consistent findings of fibrosis or substantial cellular infiltrate. Fr98-induced left ventricle dysfunction was associated with a higher virus load, increased mRNA expression of the macrophage marker F4/80, increased chemokine production, and a small number of apoptotic cells in the heart. PMID- 17855523 TI - Isolation of avian paramyxovirus 1 from a patient with a lethal case of pneumonia. AB - An unknown virus was isolated from a lung biopsy sample and multiple other samples from a patient who developed a lethal case of pneumonia following a peripheral blood stem cell transplant. A random PCR-based molecular screening method was used to identify the infectious agent as avian paramyxovirus 1 (APMV 1; a group encompassing Newcastle disease virus), which is a highly contagious poultry pathogen that has only rarely been found in human infections. Immunohistochemical analysis confirmed the presence of APMV-1 antigen in sloughed alveolar cells in lung tissue from autopsy. Sequence from the human isolate showed that it was most closely related to virulent pigeon strains of APMV-1. This is the most completely documented case of a systemic human infection caused by APMV-1 and is the first report of an association between this virus and a fatal disease in a human. PMID- 17855524 TI - Virus-encoded aminoacyl-tRNA synthetases: structural and functional characterization of mimivirus TyrRS and MetRS. AB - Aminoacyl-tRNA synthetases are pivotal in determining how the genetic code is translated in amino acids and in providing the substrate for protein synthesis. As such, they fulfill a key role in a process universally conserved in all cellular organisms from their most complex to their most reduced parasitic forms. In contrast, even complex viruses were not found to encode much translation machinery, with the exception of isolated components such as tRNAs. In this context, the discovery of four aminoacyl-tRNA synthetases encoded in the genome of mimivirus together with a full set of translation initiation, elongation, and termination factors appeared to blur what was once a clear frontier between the cellular and viral world. Functional studies of two mimivirus tRNA synthetases confirmed the MetRS specificity for methionine and the TyrRS specificity for tyrosine and conformity with the identity rules for tRNA(Tyr) for archea/eukarya. The atomic structure of the mimivirus tyrosyl-tRNA synthetase in complex with tyrosinol exhibits the typical fold and active-site organization of archaeal-type TyrRS. However, the viral enzyme presents a unique dimeric conformation and significant differences in its anticodon binding site. The present work suggests that mimivirus aminoacyl-tRNA synthetases function as regular translation enzymes in infected amoebas. Their phylogenetic classification does not suggest that they have been acquired recently by horizontal gene transfer from a cellular host but rather militates in favor of an intricate evolutionary relationship between large DNA viruses and ancestral eukaryotes. PMID- 17855525 TI - N-glycolyl GM1 ganglioside as a receptor for simian virus 40. AB - Carbohydrate microarrays have emerged as powerful tools in analyses of microbe host interactions. Using a microarray with 190 sequence-defined oligosaccharides in the form of natural glycolipids and neoglycolipids representative of diverse mammalian glycans, we examined interactions of simian virus 40 (SV40) with potential carbohydrate receptors. While the results confirmed the high specificity of SV40 for the ganglioside GM1, they also revealed that N-glycolyl GM1 ganglioside [GM1(Gc)], which is characteristic of simian species and many other nonhuman mammals, is a better ligand than the N-acetyl analog [GM1(Ac)] found in mammals, including humans. After supplementing glycolipid-deficient GM95 cells with GM1(Ac) and GM1(Gc) gangliosides and the corresponding neoglycolipids with phosphatidylethanolamine lipid groups, it was found that GM1(Gc) analogs conferred better virus binding and infectivity. Moreover, we visualized the interaction of NeuGc with VP1 protein of SV40 by molecular modeling and identified a conformation for GM1(Gc) ganglioside in complex with the virus VP1 pentamer that is compatible with its presentation as a membrane receptor. Our results open the way not only to detailed studies of SV40 infection in relation to receptor expression in host cells but also to the monitoring of changes that may occur with time in receptor usage by the virus. PMID- 17855526 TI - Fiber shaft-chimeric adenovirus vectors lacking the KKTK motif efficiently infect liver cells in vivo. AB - The molecular mechanisms governing the infectivity of adenovirus (Ad) toward specific cell and tissue types in vivo remain poorly understood. The direct Ad binding to hepatic heparan sulfate proteoglycans via the KKTK motif within the fiber shaft domain was suggested to be the major mechanism of Ad liver cell infection in vivo. Here, we describe the generation and in vitro and in vivo infectivity studies of Ad5-based vectors possessing long Ad31- or Ad41-derived fiber shaft domains, which lack the KKTK motif. We found that all the critical early steps of Ad infection, including attachment to the cellular receptor, internalization, and virus genome transfer into the nucleus, occurred with similar levels of efficiency for fiber shaft-chimeric vectors and unmodified Ad5. Upon intravenous delivery into mice, fiber shaft-chimeric vectors accumulated in liver tissue, transduced liver cells, and induced the production of proinflammatory cytokines (tumor necrosis factor alpha and interleukin-6) and the chemokine monocyte chemoattractant protein 1 at levels indistinguishable from those observed for Ad5. Thus, our data provide evidence that the Ad5 fiber shaft amino acid sequence does not play any substantial role in determining adenovirus infectivity toward hepatic cells in vivo. The data obtained contribute to improving our understanding of the molecular mechanisms determining Ad infectivity and biodistribution in vivo and may aid in designing novel Ad-based vectors for gene therapy applications. PMID- 17855527 TI - Identification of the DNA sequence interacting with Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 1. AB - Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma. The open reading frame (K9) of KSHV encodes viral interferon regulatory factor 1 (vIRF1), which functions as a repressor of interferon mediated signal transduction. The amino-terminal region of vIRF1 displays significant homology to the DNA-binding domain of cellular interferon regulatory factors, supporting the theory that the protein interacts with specific DNA sequences. Here, we identify the consensus sequence of vIRF1-binding sites from a pool of random oligonucleotides. Moreover, our data show that vIRF1 interacts with the K3:viral dihydrofolate reductase:viral interleukin 6 promoter region in the KSHV genome. PMID- 17855528 TI - Influenza virus-induced type I interferon leads to polyclonal B-cell activation but does not break down B-cell tolerance. AB - The link between infection and autoimmunity is not yet well understood. This study was designed to evaluate if an acute viral infection known to induce type I interferon production, like influenza, can by itself be responsible for the breakdown of immune tolerance and for autoimmunity. We first tested the effects of influenza virus on B cells in vitro. We then infected different transgenic mice expressing human rheumatoid factors (RF) in the absence or in the constitutive presence of the autoantigen (human immunoglobulin G [IgG]) and young lupus-prone mice [(NZB x NZW)F(1)] with influenza virus and looked for B-cell activation. In vitro, the virus induces B-cell activation through type I interferon production by non-B cells but does not directly stimulate purified B cells. In vivo, both RF and non-RF B cells were activated in an autoantigen independent manner. This activation was abortive since IgM and IgM-RF production levels were not increased in infected mice compared to uninfected controls, whether or not anti-influenza virus human IgG was detected and even after viral rechallenge. As in RF transgenic mice, acute viral infection of (NZB x NZW)F(1) mice induced only an abortive activation of B cells and no increase in autoantibody production compared to uninfected animals. Taken together, these experiments show that virus-induced acute type I interferon production is not able by itself to break down B-cell tolerance in both normal and autoimmune genetic backgrounds. PMID- 17855529 TI - Intestinal hyperplasia induced by simian virus 40 large tumor antigen requires E2F2. AB - The simian virus 40 large T antigen contributes to neoplastic transformation, in part, by targeting the Rb family of tumor suppressors. There are three known Rb proteins, pRb, p130, and p107, all of which block the cell cycle by preventing the transcription of genes regulated by the E2F family of transcription factors. T antigen interacts directly with Rb proteins and disrupts Rb-E2F complexes both in vitro and in cultured cells. Consequently, T antigen is thought to inhibit transcriptional repression by the Rb family proteins by disrupting their interaction with E2F proteins, thus allowing E2F-dependent transcription and the expression of cellular genes needed for entry into S phase. This model predicts that active E2F-dependent transcription is required for T-antigen-induced transformation. To test this hypothesis, we have examined the status of Rb-E2F complexes in murine enterocytes. Previous studies have shown that T antigen drives enterocytes into S phase, resulting in intestinal hyperplasia, and that the induction of enterocyte proliferation requires T-antigen binding to Rb proteins. In this paper, we show that normal growth-arrested enterocytes contain p130-E2F4 complexes and that T-antigen expression destroys these complexes, most likely by stimulating p130 degradation. Furthermore, unlike their normal counterparts, enterocytes expressing T antigen contain abundant levels of E2F2 and E2F3a. Concomitantly, T-antigen-induced intestinal proliferation is reduced in mice lacking either E2F2 alone or both E2F2 and E2F3a, but not in mice lacking E2F1. These studies support a model in which T antigen eliminates Rb-E2F repressive complexes so that specific activator E2Fs can drive S-phase entry. PMID- 17855530 TI - Occurrence of the European subgroup of subtype I BK polyomavirus in Japanese Americans suggests transmission outside the family. AB - To examine the mode of transmission of BK polyomavirus (BKV), urine samples were collected from Japanese-Americans in Los Angeles and from other southern Californians. Subtype I was the main subtype found in samples from both groups. The subtype I subgroup Ib-2, which is predominant in Europe, was the primary subgroup detected in second-generation Japanese-Americans and in southern Californians; however, the Ic subgroup prevalent in native Japanese was rare in these populations. Since the European subgroup (Ib-2) predominated in the studied geographic area, the findings demonstrate that transmission outside the family is common in the spread of BKV, unlike previous findings for JC polyomavirus. PMID- 17855531 TI - Lack of repeat transduction by recombinant adeno-associated virus type 5/5 vectors in the mouse airway. AB - While recombinant adeno-associated virus (rAAV) vectors promote long-term transgene expression in the lungs and other organs, the goal of correcting chronic inherited lung diseases such as cystic fibrosis with this type of viral gene transfer vector is limited by the requirement of achieving stable potent transgene expression, potentially requiring vector readministration. Here we evaluated the abilities of rAAV type 5/5 (rAAV5/5) vectors based on the genome and capsid of AAV5 to efficiently transduce the lungs and nasal epithelium of mice after repeated administration. Transduction efficiency as judged by reporter gene expression was markedly reduced on a second rAAV5/5 administration and effectively abolished on a third. Varying the period between administrations from 8 to 36 weeks did not allow efficient repeated administration. A rapid rise in anti-AAV5 antibodies was noted after rAAV5/5 vector administration that was sustained for the entire period of investigation (in some cases exceeding 9 months). Furthermore, this antibody response and subsequent failure to repeatedly administer the vector were not rescued by the in vivo expression of CTLA4Ig from an rAAV5/5 vector. These results suggest that without the development of an effective and clinically acceptable immunosuppression strategy, treatments for chronic diseases that require repeated administration of rAAV5/5 vectors will be unsuccessful. PMID- 17855532 TI - The role of NKG2D signaling in inhibition of cytotoxic T-lymphocyte lysis by the Murine cytomegalovirus immunoevasin m152/gp40. AB - Three proteins encoded by murine cytomegalovirus (MCMV) -- gp34, encoded by m04 (m04/gp34), gp48, encoded by m06 (m06/gp48), and gp40, encoded by m152 (m152/gp40) -- act together to powerfully impact the ability of primed cytotoxic CD8 T lymphocytes (CTL) to kill virus-infected cells. Of these three, the impact of m152/gp40 on CTL lysis appears greater than would be expected based on its impact on cell surface major histocompatibility complex (MHC) class I. In addition to MHC class I, m152/gp40 also downregulates the RAE-1 family of NKG2D ligands, which can provide costimulation for CD8 T cells. We hypothesized that m152/gp40 may impact CTL lysis so profoundly because it inhibits both antigen presentation and NKG2D-mediated costimulation. We therefore tested the extent to which m152/gp40's ability to inhibit CTL lysis of MCMV-infected cells could be accounted for by its inhibition of NKG2D signaling. As was predictable from the results reported in the literature, NKG2D ligands were not detected by NKG2D tetramer staining of cells infected with wild-type MCMV, whereas those infected with MCMV lacking m152/gp40 displayed measurable levels of the NKG2D ligand. To determine whether NKG2D signaling contributed to the ability of CTL to lyse these cells, we used a blocking anti-NKG2D antibody. Blocking NKG2D signaling did affect the killing of MCMV-infected cells for some epitopes. However, for all epitopes, the impact of m152/gp40 on CTL lysis was much greater than the impact of inhibition of NKG2D signaling. We conclude that the downregulation of NKG2D ligands by MCMV makes only a small contribution to the impact of m152/gp40 on CTL lysis and only for a small subset of CTL. PMID- 17855533 TI - Selection and analysis of mutations in an encephalomyocarditis virus internal ribosome entry site that improve the efficiency of a bicistronic flavivirus construct. AB - Flaviviruses have a positive-stranded RNA genome, which simultaneously serves as an mRNA for translation of the viral proteins. All of the structural and nonstructural proteins are translated from a cap-dependent cistron as a single polyprotein precursor. In an earlier study (K. K. Orlinger, V. M. Hoenninger, R. M. Kofler, and C. W. Mandl, J. Virol. 80:12197-12208, 2006), it was demonstrated that an artificial bicistronic flavivirus genome, TBEV-bc, in which the region coding for the viral surface glycoproteins prM and E from tick-borne encephalitis virus (TBEV) had been removed from its natural context and inserted into the 3' noncoding region under the control of an internal ribosome entry site (IRES) from encephalomyocarditis virus (EMCV) produces viable, infectious virus when cells are transfected with this RNA. The rates of RNA replication and infectious particle formation were significantly lower with TBEV-bc, however, than with wild type TBEV. In this study, we have identified two types of mutations, selected by passage in BHK-21 cells, that enhance the growth properties of TBEV-bc. The first type occurred in the E protein, and these most likely increase the affinity of the virus for heparan sulfate on the cell surface. The second type occurred in the inserted EMCV IRES, in the oligo(A) loop of the J-K stem-loop structure, a binding site for the eukaryotic translation initiation factor 4G. These included single-nucleotide substitutions as well as insertions of additional adenines in this loop. An A-to-C substitution in the oligo(A) loop decreased the efficiency of the IRES itself but nevertheless resulted in improved rates of virus particle formation and overall replication efficiency. These results demonstrate the need for proper balance in the competition for free template RNA between the viral RNA replication machinery and the cellular translation machinery at the two different start sites and also identify specific target sites for the improvement of bicistronic flavivirus expression vectors. PMID- 17855534 TI - Mutations in envelope gp120 can impact proteolytic processing of the gp160 precursor and thereby affect neutralization sensitivity of human immunodeficiency virus type 1 pseudoviruses. AB - The design of an efficient human immunodeficiency virus (HIV) immunogen able to generate broad neutralizing antibodies (NAbs) remains an elusive goal. As more data emerge, it is becoming apparent that one important aspect of such an immunogen will be the proper representation of the envelope protein (Env) as it exists on native virions. Important questions that are yet to be fully addressed include what factors dictate Env processing, how different Env forms are represented on the virion, and ultimately how these issues influence the development and efficacy of NAbs. Recent data have begun to illuminate the extent to which changes in gp41 can impact the overall structure and neutralizing sensitivity of Env. Here, we present evidence to suggest that minor mutations in gp120 can significantly impact Env processing. We analyzed the gp120 sequences of 20 env variants that evolved in multiple macaques over 8 months of infection with simian/human immunodeficiency virus 89.6P. Variant gp120 sequences were subcloned into gp160 expression plasmids with identical cleavage motifs and gp41 sequences. Cells cotransfected with these plasmids and delta env genomes were able to produce competent virus. The resulting pseudoviruses incorporated high levels of Env onto virions that exhibited a range of degrees of virion-associated Env cleavage (15 to 40%). Higher levels of cleavage correlated with increased infectivity and increased resistance to macaque plasma, HIV immunoglobulin, soluble CD4, and human monoclonal antibodies 4E10, 2F5, and b12. Based on these data, we discuss a model whereby changes in gp120 of 89.6P impact Env processing and thereby mediate escape from a range of neutralizing agents. PMID- 17855535 TI - Human rhinovirus type 14 gain-of-function mutants for oriI utilization define residues of 3C(D) and 3Dpol that contribute to assembly and stability of the picornavirus VPg uridylylation complex. AB - VPg linkage to the 5' ends of picornavirus RNAs requires production of VPg-pUpU. VPg-pUpU is templated by an RNA stem-loop (the cre or oriI) found at different locations in picornavirus genomes. At least one adaptive mutation is required for human rhinovirus type 14 (HRV-14) to use poliovirus type 3 (PV-3) or PV-1 oriI efficiently. One mutation changes Leu-94 of 3C to Pro; the other changes Asp-406 of 3Dpol to Asn. By using an in vitro VPg uridylylation system for HRV-14 that recapitulates biological phenotypes, we show that the 3C adaptive mutation functions at the level of 3C(D) and the 3D adaptive mutation functions at the level of 3Dpol. Pro-94 3C(D) has an expanded specificity and enhanced stability relative to wild-type 3C(D) that leads to production of more processive uridylylation complexes. PV-1/HRV-14 oriI chimeras reveal sequence specificity in 3C(D) recognition of oriI that resides in the upper stem. Asn-406 3Dpol is as active as wild-type 3Dpol in RNA-primed reactions but exhibits greater VPg uridylylation activity due to more efficient recruitment to and retention in the VPg uridylylation complex. Asn-406 3Dpol from PV-1 exhibits identical behavior. These studies suggest a two-step binding mechanism in the assembly of the 3C(D) oriI complex that leads to unwinding of at least the upper stem of oriI and provide additional support for a direct interaction between the back of the thumb of 3Dpol and 3C that is required for 3Dpol recruitment to and retention in the uridylylation complex. PMID- 17855536 TI - Phylogenetic diversity among low-virulence newcastle disease viruses from waterfowl and shorebirds and comparison of genotype distributions to those of poultry-origin isolates. AB - Low-virulence Newcastle disease viruses (loNDV) are frequently recovered from wild bird species, but little is known about their distribution, genetic diversity, or potential to cause disease in poultry. NDV isolates recovered from cloacal samples of apparently healthy waterfowl and shorebirds (WS) in the United States during 1986 to 2005 were examined for genomic diversity and their potential for virulence (n = 249). In addition 19 loNDV isolates from U.S. live bird markets (LBMs) were analyzed and found to be genetically distinct from NDV used in live vaccines but related to WS-origin NDV. Phylogenetic analysis of the fusion protein identified nine novel genotypes among the class I NDV, and new genomic subgroups were identified among genotypes I and II of the class II viruses. The WS-origin viruses exhibited broad genetic and antigenic diversity, and some WS genotypes displayed a closer phylogenetic relationship to LBM-origin NDV. All NDV were predicted to be lentogenic based upon sequencing of the fusion cleavage site, intracerebral pathogenicity index, or mean death time in embryo assays. The USDA real-time reverse transcription-PCR assay, which targets the matrix gene, identified nearly all of the class II NDV tested but failed to detect class I viruses from both LBM and WS. The close phylogenetic proximity of some WS and LBM loNDV suggests that viral transmission may occur among wild birds and poultry; however, these events may occur unnoticed due to the broad genetic diversity of loNDV, the lentogenic presentation in birds, and the limitations of current rapid diagnostic tools. PMID- 17855537 TI - Natural regulatory T cells and persistent viral infection. PMID- 17855538 TI - Analysis of the role of autophagy in replication of herpes simplex virus in cell culture. AB - The herpes simplex virus type 1 (HSV-1) neurovirulence gene encoding ICP34.5 controls the autophagy pathway. HSV-1 strains lacking ICP34.5 are attenuated in growth and pathogenesis in animal models and in primary cultured cells. While this growth defect has been attributed to the inability of an ICP34.5-null virus to counteract the induction of translational arrest through the PKR antiviral pathway, the role of autophagy in the regulation of HSV-1 replication is unknown. Here we show that HSV-1 infection induces autophagy in primary murine embryonic fibroblasts and that autophagosome formation is increased to a greater extent following infection with an ICP34.5-deficient virus. Elimination of the autophagic pathway did not significantly alter the replication of wild-type HSV-1 or ICP34.5 mutants. The phosphorylation state of eIF2alpha and viral protein accumulation were unchanged in HSV-1-infected cells unable to undergo autophagy. These data show that while ICP34.5 regulates autophagy, it is the prevention of translational arrest by ICP34.5 rather than its control of autophagy that is the pivotal determinant of efficient HSV-1 replication in primary cell culture. PMID- 17855539 TI - Suppression of viremia and evolution of human immunodeficiency virus type 1 drug resistance in a macaque model for antiretroviral therapy. AB - Antiretroviral therapy (ART) in human immunodeficiency virus type 1 (HIV-1) infected patients does not clear the infection and can select for drug resistance over time. Not only is drug-resistant HIV-1 a concern for infected individuals on continual therapy, but it is an emerging problem in resource-limited settings where, in efforts to stem mother-to-child-transmission of HIV-1, transient nonnucleoside reverse transcriptase inhibitor (NNRTI) therapy given during labor can select for NNRTI resistance in both mother and child. Questions of HIV-1 persistence and drug resistance are highly amenable to exploration within animals models, where therapy manipulation is less constrained. We examined a pigtail macaque infection model responsive to anti-HIV-1 therapy to study the development of resistance. Pigtail macaques were infected with a pathogenic simian immunodeficiency virus encoding HIV-1 reverse transcriptase (RT-SHIV) to examine the impact of prior exposure to a NNRTI on subsequent ART comprised of a NNRTI and two nucleoside RT inhibitors. K103N resistance-conferring mutations in RT rapidly accumulated in 2/3 infected animals after NNRTI monotherapy and contributed to virologic failure during ART in 1/3 animals. By contrast, ART effectively suppressed RT-SHIV in 5/6 animals. These data indicate that suboptimal therapy facilitates HIV-1 drug resistance and suggest that this model can be used to investigate persisting viral reservoirs. PMID- 17855540 TI - De novo synthesis of N and P proteins as a key step in Sendai virus gene expression. AB - Among the members of the paramyxovirus family, the transcription process and the components involved have been studied under in vitro conditions thus far. Here, we reexamined the function of the viral RNA-dependent RNA polymerase through infection studies with Sendai virus (SeV) N and P deletion (Delta) mutants. To elucidate solely transcription-specific processes, all virus mutants also were rendered deficient in genome replication. Using mutant SeV DeltaP, the earlier suspected supplemental role of P protein was clearly demonstrated to be essential during viral gene expression. Moreover, when SeV DeltaN or DeltaN PDelta2-77 (with the 5' end of the P gene deleted) mutant was used for infections, a completely unexpected new and essential role for N protein was discovered for viral gene expression. In the early phases of an infection and in the absence of de novo viral protein synthesis, primary transcription occurs at hardly detectable levels. In contrast, if newly synthesized N protein is present, primary viral transcription reaches normal levels. From our data, we conclude that de novo synthesis of SeV N and P proteins is a key step for viral gene expression that facilitates the transition from preliminary to normal primary transcriptional activity. PMID- 17855541 TI - Human immunodeficiency virus type 1 Vpr links proteasomal degradation and checkpoint activation. PMID- 17855542 TI - Neuraminidase inhibitor-resistant recombinant A/Vietnam/1203/04 (H5N1) influenza viruses retain their replication efficiency and pathogenicity in vitro and in vivo. AB - Effective antiviral drugs are essential for early control of an influenza pandemic. It is therefore crucial to evaluate the possible threat posed by neuraminidase (NA) inhibitor-resistant influenza viruses with pandemic potential. Four NA mutations (E119G, H274Y, R292K, and N294S) that have been reported to confer resistance to NA inhibitors were each introduced into recombinant A/Vietnam/1203/04 (VN1203) H5N1 influenza virus. For comparison, the same mutations were introduced into recombinant A/Puerto Rico/8/34 (PR8) H1N1 influenza virus. The E119G and R292K mutations significantly compromised viral growth in vitro, but the H274Y and N294S mutations were stably maintained in VN1203 and PR8 viruses. In both backgrounds, the H274Y and N294S mutations conferred resistance to oseltamivir carboxylate (50% inhibitory concentration [IC(50)] increases, >250-fold and >20-fold, respectively), and the N294S mutation reduced susceptibility to zanamivir (IC(50) increase, >3.0-fold). Although the H274Y and N294S mutations did not compromise the replication efficiency of VN1203 or PR8 viruses in vitro, these mutations slightly reduced the lethality of PR8 virus in mice. However, the VN1203 virus carrying either the H274Y or N294S mutation exhibited lethality similar to that of the wild-type VN1203 virus. The different enzyme kinetic parameters (V(max) and K(m)) of avian-like VN1203 NA and human-like PR8 NA suggest that resistance-associated NA mutations can cause different levels of functional loss in NA glycoproteins of the same subtype. Our results suggest that NA inhibitor-resistant H5N1 variants may retain the high pathogenicity of the wild-type virus in mammalian species. Patients receiving NA inhibitors for H5N1 influenza virus infection should be closely monitored for the emergence of resistant variants. PMID- 17855543 TI - Analysis of the interaction of primate retroviruses with the human RNA interference machinery. AB - The question of whether retroviruses, including human immunodeficiency virus type 1 (HIV-1), interact with the cellular RNA interference machinery has been controversial. Here, we present data showing that neither HIV-1 nor human T-cell leukemia virus type 1 (HTLV-1) expresses significant levels of either small interfering RNAs or microRNAs in persistently infected T cells. We also demonstrate that the retroviral nuclear transcription factors HIV-1 Tat and HTLV 1 Tax, as well as the Tas transactivator encoded by primate foamy virus, fail to inhibit RNA interference in human cells. Moreover, the stable expression of physiological levels of HIV-1 Tat did not globally inhibit microRNA production or expression in infected human cells. Together, these data argue that HIV-1 and HTLV-1 neither induce the production of viral small interfering RNAs or microRNAs nor repress the cellular RNA interference machinery in infected cells. PMID- 17855544 TI - Mutational analysis of the N-terminal domain of Moloney murine leukemia virus capsid protein. AB - Retroviral capsid (CA) proteins contain a structurally conserved N-terminal domain (NTD) consisting of a beta-hairpin and six to seven alpha-helices. To examine the role of this domain in Moloney murine leukemia virus (MoMLV) replication, we analyzed 18 insertional mutations in this region. All mutants were noninfectious. Based on the results of this analysis and our previous studies on additional mutations in this domain, we were able to divide the NTD of MoMLV CA into three functional regions. The first functional region included the region near the N terminus that forms the beta-hairpin and was shown to control normal maturation of virions. The second region included the helix 4/5 loop and was essential for the formation of spherical cores. The third region encompassed most of the NTD except for the above loop. Mutants of this region assembled imperfect cores, as seen by detailed electron microscopy analyses, yet the resulting particles were efficiently released from cells. The mutants were defective at a stage immediately following entry of the core into cells. Despite possessing functional reverse transcriptase machinery, these mutant virions did not initiate reverse transcription in cells. This block could be due to structural defects in the assembling core or failure of an essential host protein to interact with the mutant CA protein, both of which may prevent correct disassembly upon entry of the virus into cells. Future studies are needed to understand the mechanism of these blocks and to target these regions pharmacologically to inhibit retroviral infection at additional stages. PMID- 17855545 TI - Characterization of a broadly reactive monoclonal antibody against norovirus genogroups I and II: recognition of a novel conformational epitope. AB - Norovirus, which belongs to the family Caliciviridae, is one of the major causes of nonbacterial acute gastroenteritis in the world. The main human noroviruses are of genogroup I (GI) and genogroup II (GII), which were subdivided further into at least 15 and 18 genotypes (GI/1 to GI/15 and GII/1 to GII/18), respectively. The development of immunological diagnosis for norovirus had been hindered by the antigen specificity of the polyclonal antibody. Therefore, several laboratories have produced broadly reactive monoclonal antibodies, which recognize the linear GI and GII cross-reactive epitopes or the conformational GI specific epitope. In this study, we characterized the novel monoclonal antibody 14-1 (MAb14-1) for further development of the rapid immunochromatography test. Our results demonstrated that MAb14-1 could recognize 15 recombinant virus-like particles (GI/1, 4, 8, and 11 and GII/1 to 7 and 12 to 15) and showed weak affinity to the virus-like particle of GI/3. This recognition range is the broadest of the existing monoclonal antibodies. The epitope for MAb14-1 was identified by fragment, sequence, structural, and mutational analyses. Both terminal antigenic regions (amino acid positions 418 to 426 and 526 to 534) on the C-terminal P1 domain formed the conformational epitope and were in the proximity of the insertion region (positions 427 to 525). These regions contained six amino acids responsible for antigenicity that were conserved among genogroup(s), genus, and Caliciviridae. This epitope mapping explained the broad reactivity and different titers among GI and GII. To our knowledge, we are the first group to identify the GI and GII cross-reactive monoclonal antibody, which recognizes the novel conformational epitope. From these data, MAb14-1 could be used further to develop immunochromatography. PMID- 17855546 TI - Human immunodeficiency virus type 1 and influenza virus exit via different membrane microdomains. AB - Directed release of human immunodeficiency virus type 1 (HIV-1) into the cleft of the virological synapse that can form between infected and uninfected T cells, for example, in lymph nodes, is thought to contribute to the systemic spread of this virus. In contrast, influenza virus, which causes local infections, is shed into the airways of the respiratory tract from free surfaces of epithelial cells. We now demonstrate that such differential release of HIV-1 and influenza virus is paralleled, at the subcellular level, by viral assembly at different microsegments of the plasma membrane of HeLa cells. HIV-1, but not influenza virus, buds through microdomains containing the tetraspanins CD9 and CD63. Consequently, the anti-CD9 antibody K41, which redistributes its antigen and also other tetraspanins to cell-cell adhesion sites, interferes with HIV-1 but not with influenza virus release. Altogether, these data strongly suggest that the bimodal egress of these two pathogenic viruses, like their entry into target cells, is guided by specific sets of host cell proteins. PMID- 17855547 TI - Varicella-zoster virus modulates NF-kappaB recruitment on selected cellular promoters. AB - Intercellular adhesion molecule 1 (ICAM-1) expression is down-regulated in the center of cutaneous varicella lesions despite the expression of proinflammatory cytokines such as gamma interferon and tumor necrosis factor alpha (TNF-alpha). To study the molecular basis of this down-regulation, the ICAM-1 induction of TNF alpha was analyzed in varicella-zoster virus (VZV)-infected melanoma cells (MeWo), leading to the following observations: (i) VZV inhibits the stimulation of icam-1 mRNA synthesis; (ii) despite VZV-induced nuclear translocation of p65, p52, and c-Rel, p50 does not translocate in response to TNF-alpha; (iii) the nuclear p65 present in VZV-infected cells is no longer associated with p50 and is unable to bind the proximal NF-kappaB site of the icam-1 promoter, despite an increased acetylation and accessibility of the promoter in response to TNF-alpha; and (iv) VZV induces the nuclear accumulation of the NF-kappaB inhibitor p100. VZV also inhibits icam-1 stimulation of TNF-alpha by strongly reducing NF-kappaB nuclear translocation in MRC5 fibroblasts. Taken together, these data show that VZV interferes with several aspects of the immune response by inhibiting NF kappaB binding and the expression of target genes. Targeting NF-kappaB activation, which plays a central role in innate and adaptive immune responses, leads to obvious advantages for the virus, particularly in melanocytes, which are a site of viral replication in the skin. PMID- 17855548 TI - Genetic analysis of Murine hepatitis virus nsp4 in virus replication. AB - Coronavirus replicase polyproteins are translated from the genomic positive strand RNA and are proteolytically processed by three viral proteases to yield 16 mature nonstructural proteins (nsp1 to nsp16). nsp4 contains four predicted transmembrane-spanning regions (TM1, -2, -3, and -4), demonstrates characteristics of an integral membrane protein, and is thought to be essential for the formation and function of viral replication complexes on cellular membranes. To determine the requirement of nsp4 for murine hepatitis virus (MHV) infection in culture, engineered deletions and mutations in TMs and intervening soluble regions were analyzed for effects on virus recovery, growth, RNA synthesis, protein expression, and intracellular membrane modifications. In-frame partial or complete deletions of nsp4; deletions of TM1, -2, and -3; and alanine substitutions of multiple conserved, clustered, charged residues in nsp4 resulted in viruses that were nonrecoverable, viruses highly impaired in growth and RNA synthesis, and viruses that were nearly wild type in replication. The results indicate that nsp4 is required for MHV replication and that while putative TM1, 2, and -3 and specific charged residues may be essential for productive virus infection, putative TM4 and the carboxy-terminal amino acids K(398) through T(492) of nsp4 are dispensable. Together, the experiments identify important residues and regions for studies of nsp4 topology, function, and interactions. PMID- 17855549 TI - Highly pathogenic avian influenza H5N1 viruses elicit an attenuated type i interferon response in polarized human bronchial epithelial cells. AB - The unparalleled spread of highly pathogenic avian influenza A (HPAI) H5N1 viruses has resulted in devastating outbreaks in domestic poultry and sporadic human infections with a high fatality rate. To better understand the mechanism(s) of H5N1 virus pathogenesis and host responses in humans, we utilized a polarized human bronchial epithelial cell model that expresses both avian alpha-2,3- and human alpha-2,6-linked sialic acid receptors on the apical surface and supports productive replication of both H5N1 and H3N2 viruses. Using this model, we compared the abilities of selected 2004 HPAI H5N1 viruses isolated from humans and a recent human H3N2 virus to trigger the type I interferon (IFN) response. H5N1 viruses elicited significantly less IFN regulatory factor 3 (IRF3) nuclear translocation, as well as delayed and reduced production of IFN-beta compared with the H3N2 virus. Furthermore, phosphorylation of Stat2 and induction of IFN stimulated genes (ISGs), such as MX1, ISG15, IRF7, and retinoic acid-inducible gene I, were substantially delayed and reduced in cells infected with H5N1 viruses. We also observed that the highly virulent H5N1 virus replicated more efficiently and induced a weaker IFN response than the H5N1 virus that exhibited low virulence in mammals in an earlier study. Our data suggest that the H5N1 viruses tested, especially the virus with the high-pathogenicity phenotype, possess greater capability to attenuate the type I IFN response than the human H3N2 virus. The attenuation of this critical host innate immune defense may contribute to the virulence of H5N1 viruses observed in humans. PMID- 17855550 TI - Interleukin-7 enhances proliferation responses to T-cell receptor stimulation in naive CD4+ T cells from human immunodeficiency virus-infected persons. AB - Proliferation responses of naive CD4(+) T cells to T-cell receptor and interleukin-7 (IL-7) stimulation were evaluated by using cells from human immunodeficiency virus-positive (HIV(+)) donors. IL-7 enhanced responses to T cell receptor stimulation, and the magnitude of this enhancement was similar in cells from healthy controls and from HIV(+) subjects. The overall response to T cell receptor stimulation alone or in combination with IL-7, however, was diminished among viremic HIV(+) donors and occurred independent of antigen presenting cells. Frequencies of CD127(+) cells were related to the magnitudes of proliferation enhancement that were mediated by IL-7. Thus, IL-7 enhances but does not fully restore the function of naive CD4(+) T cells from HIV-infected persons. PMID- 17855551 TI - Norwalk virus RNA is infectious in mammalian cells. AB - Human noroviruses are positive-sense RNA viruses and are the leading cause of epidemic acute viral gastroenteritis in developed countries. The absence of an in vitro cell culture model for human norovirus infection has limited the development of effective antivirals and vaccines. Human histo-blood group antigens have been regarded as receptors for norovirus infection, and expression of the alpha(1,2) fucosyltransferase gene (FUT2) responsible for the secretor phenotype is required for susceptibility to Norwalk virus (NV) infection. We report for the first time that transfection of NV RNA, isolated from stool samples from human volunteers, into human hepatoma Huh-7 cells leads to viral replication, with expression of viral antigens, RNA replication, and release of viral particles into the medium. Prior treatment of the RNA with proteinase K completely abolishes RNA infectivity, suggesting a key role of an RNA-protein complex. Although overexpression of the human FUT2 gene enhances virus binding to cells, it is not sufficient to allow a complete viral infection, and viral spread from NV-transfected cells to naive cells does not occur. Finally, no differences in NV RNA replication are observed between Huh-7 and Huh-7.5.1 cells, which contain an inactivating mutation in retinoic acid-inducible gene I (RIG-I), suggesting that the RIG-I pathway does not play a role in limiting NV replication. Our results strongly suggest that the block(s) to NV replication in vitro is at the stage of receptor and/or coreceptor binding and/or uncoating, either because cells lack some specific factor or activation of cellular antiviral responses independent of RIG-I inhibits virus replication. PMID- 17855552 TI - Relaxed repression of herpes simplex virus type 1 genomes in Murine trigeminal neurons. AB - The expression of herpes simplex virus (HSV) genomes in the absence of viral regulatory proteins in sensory neurons is poorly understood. Previously, our group reported an HSV immediate early (IE) mutant (d109) unable to express any of the five IE genes and encoding a model human cytomegalovirus immediate early promoter-green fluorescent protein (GFP) transgene. In cultured cells, GFP expressed from this mutant was observed in only a subset of infected cells. The subset exhibited cell type dependence, as the fractions of GFP-expressing cells varied widely among the cell types examined. Herein, we characterize this mutant in murine embryonic trigeminal ganglion (TG) cultures. We found that d109 was nontoxic to neural cultures and persisted in the cultures throughout their life spans. Unlike with some of the cultured cell lines and strains, expression of the GFP transgene was observed in a surprisingly large subset of neurons. However, very few nonneuronal cells expressed GFP. The abilities of ICP0 and an inhibitor of histone deacetylase, trichostatin A (TSA), to activate GFP expression from nonexpressing cells were also compared. The provision of ICP0 by infection with d105 reactivated quiescent genomes in nearly every cell, whereas reactivation by TSA was much more limited and restricted to the previously nonexpressing neurons. Moreover, we found that d109, which does not express ICP0, consistently reactivated HSV type 1 (KOS) in latently infected adult TG cultures. These results suggest that the state of persisting HSV genomes in some TG neurons may be more dynamic and more easily activated than has been observed with nonneuronal cells. PMID- 17855553 TI - Influenza virus mRNA translation revisited: is the eIF4E cap-binding factor required for viral mRNA translation? AB - Influenza virus mRNAs bear a short capped oligonucleotide sequence at their 5' ends derived from the host cell pre-mRNAs by a "cap-snatching" mechanism, followed immediately by a common viral sequence. At their 3' ends, they contain a poly(A) tail. Although cellular and viral mRNAs are structurally similar, influenza virus promotes the selective translation of its mRNAs despite the inhibition of host cell protein synthesis. The viral polymerase performs the cap snatching and binds selectively to the 5' common viral sequence. As viral mRNAs are recognized by their own cap-binding complex, we tested whether viral mRNA translation occurs without the contribution of the eIF4E protein, the cellular factor required for cap-dependent translation. Here, we show that influenza virus infection proceeds normally in different situations of functional impairment of the eIF4E factor. In addition, influenza virus polymerase binds to translation preinitiation complexes, and furthermore, under conditions of decreased eIF4GI association to cap structures, an increase in eIF4GI binding to these structures was found upon influenza virus infection. This is the first report providing evidence that influenza virus mRNA translation proceeds independently of a fully active translation initiation factor (eIF4E). The data reported are in agreement with a role of viral polymerase as a substitute for the eIF4E factor for viral mRNA translation. PMID- 17855554 TI - Modified vaccinia virus Ankara induces Toll-like receptor-independent type I interferon responses. AB - Modified vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus strain undergoing clinical evaluation as a replication-deficient vaccine vector against various infections and tumor diseases. To analyze the basis of its high immunogenicity, we investigated the mechanism of how MVA induces type I interferon (IFN) responses. MVA stimulation of bone marrow-derived dendritic cells (DC) showed that plasmacytoid DC were main alpha IFN (IFN-alpha) producers that were triggered independently of productive infection, viral replication, or intermediate and late viral gene expression. Increased IFN-alpha levels were induced upon treatment with mildly UV-irradiated MVA, suggesting that a virus encoded immune modulator(s) interfered with the host cytokine response. Mice devoid of Toll-like receptor 9 (TLR9), the receptor for double-stranded DNA, mounted normal IFN-alpha responses upon MVA treatment. Furthermore, mice devoid of the adaptors of TLR signaling MyD88 and TRIF and mice deficient in protein kinase R (PKR) showed IFN-alpha responses that were only slightly reduced compared to those of wild-type mice. MVA-induced IFN-alpha responses were critically dependent on autocrine/paracrine triggering of the IFN-alpha/beta receptor and were independent of IFN-beta, thus involving "one-half" of a positive-feedback loop. In conclusion, MVA-mediated type I IFN secretion was primarily triggered by non-TLR molecules, was independent of virus propagation, and critically involved IFN feedback stimulation. These data provide the basis to further improve MVA as a vaccine vector. PMID- 17855555 TI - Interferons and ribavirin effectively inhibit Norwalk virus replication in replicon-bearing cells. AB - The development of effective therapies for noroviral gastroenteritis has been hampered by the absence of a cell culture system. Recently, we reported the generation of Norwalk virus (NV) replicon-bearing cells in BHK21 and Huh-7 cells and demonstrated that alpha interferon (IFN-alpha) effectively inhibited the replication of NV in these cells. In continuing studies for screening potential antinoroviral agents, we tested IFN-gamma and ribavirin for their effects on NV replication in the cells. Like IFN-alpha, IFN-gamma inhibited the replication of NV in the replicon-bearing cells, showing the reduction of the NV genome and proteins in a dose-dependent manner. The effective dose for reducing 50% (ED(50)) of the NV genome and protein was calculated to be approximately 40 units/ml. When ribavirin was applied to the cells, it effectively reduced the NV genome and protein with the ED(50) calculated as approximately 40 microM. The combination of IFN-alpha and ribavirin showed additive effects on the inhibition of NV replication. With the addition of guanosine to the ribavirin treatment, moderately reversed antiviral effects were observed, suggesting that the ribavirin effect may be associated with the depletion of GTP in the cells. Sequencing analysis of the conserved polymerase regions of NV in the ribavirin treated (100 microM) and nontreated groups showed that the mutation rates were similar and indicated that ribavirin did not induce catastrophic mutations. The NV replicon-bearing cells provide an excellent tool for screening potential antinoroviral agents, and our results indicated that IFNs and ribavirin may be good therapeutic options for noroviral gastroenteritis. PMID- 17855556 TI - Ancient DNA, pig domestication, and the spread of the Neolithic into Europe. AB - The Neolithic Revolution began 11,000 years ago in the Near East and preceded a westward migration into Europe of distinctive cultural groups and their agricultural economies, including domesticated animals and plants. Despite decades of research, no consensus has emerged about the extent of admixture between the indigenous and exotic populations or the degree to which the appearance of specific components of the "Neolithic cultural package" in Europe reflects truly independent development. Here, through the use of mitochondrial DNA from 323 modern and 221 ancient pig specimens sampled across western Eurasia, we demonstrate that domestic pigs of Near Eastern ancestry were definitely introduced into Europe during the Neolithic (potentially along two separate routes), reaching the Paris Basin by at least the early 4th millennium B.C. Local European wild boar were also domesticated by this time, possibly as a direct consequence of the introduction of Near Eastern domestic pigs. Once domesticated, European pigs rapidly replaced the introduced domestic pigs of Near Eastern origin throughout Europe. Domestic pigs formed a key component of the Neolithic Revolution, and this detailed genetic record of their origins reveals a complex set of interactions and processes during the spread of early farmers into Europe. PMID- 17855557 TI - MicroRNAs regulate synthesis of the neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells. AB - MicroRNAs (miRNAs) are a class of 19- to 23-nt, small, noncoding RNAs, which bind the 3' UTR of target mRNAs to mediate translational repression in animals. miRNAs have been shown to regulate developmental processes, such as self-renewal of stem cells, neuronal differentiation, myogenesis, and cancer. A functional role of miRNAs in the regulation of neurotransmitter synthesis has yet to be ascribed. We used mesenchymal stem cells (MSCs) as a model to study miRNA-mediated neurotransmitter regulation in developing neuronal cells. MSCs are mesoderm derived cells, primarily resident in adult bone marrow, which can generate functional neuronal cells. We have previously shown that human MSC-derived neuronal cells express the neurotransmitter gene, Tac1, but do not synthesize the gene's encoded peptide, the neurotransmitter substance P (SP), unless stimulated with the inflammatory mediator IL-1alpha. These findings suggested a potential role for miRNAs in the regulation of SP synthesis. Here, we report on the miRNA profile of undifferentiated human MSCs and MSC-derived neuronal cells by using miRNA-specific bioarrays. miRNAs that were increased in the neuronal cells and decreased after IL-1alpha stimulation were analyzed by the miRanda algorithm to predict Tac1 mRNA targets. Putative miR-130a, miR-206, and miR-302a binding sites were predicted within the 3' UTR of Tac1. Target validation using a luciferase reporter system confirmed the miR-130a and miR-206 sites. Specific inhibition of miR-130a and miR-206 in the neuronal cells resulted in SP synthesis and release. The studies provide a different approach in ascribing a new regulatory role for miRNAs in regulating neurotransmitter synthesis. PMID- 17855558 TI - Sweet taste signaling in the gut. PMID- 17855559 TI - Coupling of predation intensity and global diversity over geologic time. PMID- 17855560 TI - Insulin gene mutations as a cause of permanent neonatal diabetes. AB - We report 10 heterozygous mutations in the human insulin gene in 16 probands with neonatal diabetes. A combination of linkage and a candidate gene approach in a family with four diabetic members led to the identification of the initial INS gene mutation. The mutations are inherited in an autosomal dominant manner in this and two other small families whereas the mutations in the other 13 patients are de novo. Diabetes presented in probands at a median age of 9 weeks, usually with diabetic ketoacidosis or marked hyperglycemia, was not associated with beta cell autoantibodies, and was treated from diagnosis with insulin. The mutations are in critical regions of the preproinsulin molecule, and we predict that they prevent normal folding and progression of proinsulin in the insulin secretory pathway. The abnormally folded proinsulin molecule may induce the unfolded protein response and undergo degradation in the endoplasmic reticulum, leading to severe endoplasmic reticulum stress and potentially beta cell death by apoptosis. This process has been described in both the Akita and Munich mouse models that have dominant-acting missense mutations in the Ins2 gene, leading to loss of beta cell function and mass. One of the human mutations we report here is identical to that in the Akita mouse. The identification of insulin mutations as a cause of neonatal diabetes will facilitate the diagnosis and possibly, in time, treatment of this disorder. PMID- 17855561 TI - Targeted cleavage: tuneable cis-cleaving ribozymes. PMID- 17855562 TI - Inhibition of histone deacetylase activity induces developmental plasticity in oligodendrocyte precursor cells. AB - Recently, it was demonstrated that lineage-committed oligodendrocyte precursor cells (OPCs) can be converted to multipotent neural stem-like cells, capable of generating both neurons and glia after exposure to bone morphogenetic proteins. In an effort to understand and control the developmental plasticity of OPCs, we developed a high-throughput screen to identify novel chemical inducers of OPC reprogramming. Using this system, we discovered that inhibition of histone deacetylase (HDAC) activity in OPCs acts as a priming event in the induction of developmental plasticity, thereby expanding the differentiation potential to include the neuronal lineage. This conversion was found to be mediated, in part, through reactivation of sox2 and was highly reproducible at the clonal level. Further, genome-wide expression analysis demonstrated that HDAC inhibitor treatment activated sox2 and 12 other genes that identify or maintain the neural stem cell state while simultaneously silencing a large group of oligodendrocyte lineage-specific genes. This series of experiments demonstrates that global histone acetylation, induced by HDAC inhibition, can partially reverse the lineage restriction of OPCs, thereby inducing developmental plasticity. PMID- 17855563 TI - Getting specificity from simplicity in putative proteins from the prebiotic earth. AB - Can unique protein structures arise from a limited set of amino acids present on the prebiotic earth? To address this question, we have determined the stability and structure of KIA7, a 20-residue polypeptide containing chiefly Lys, Ile, and Ala. NMR methods reveal that KIA7 tetramerizes and folds on the millisecond time scale to adopt a four-helix X-bundle structure with a tightly and specifically packed core. Denaturation studies and hydrogen exchange measurements of KIA7 and several variants demonstrate that ridges-into-grooves packing of Ala and Ile side chains and the packing of a C-terminal aromatic group into the hydrophobic core are sufficient to give rise to a rather stable, well folded protein structure, with no favorable electrostatic interactions or tertiary or quaternary hydrogen bonds. Both modern proteins and RNAs can adopt specific structures, but RNAs do so with a limited "alphabet" of residues and types of stabilizing interactions. The results reported here show that specific, well folded protein structures can also arise from a highly reduced set of stabilizing interactions and amino acids that are thought to have been present on the prebiotic earth. PMID- 17855564 TI - Activation of naturally occurring lung CD4(+)CD25(+) regulatory T cells requires CD8 and MHC I interaction. AB - Naturally occurring Foxp3(+)CD4(+)CD25(+) T cells (nTregs) isolated from lungs of naive mice regulate allergic airway hyperresponsiveness (AHR) and inflammation. Here, we demonstrate the critical requirement for engagement of MHC class I on CD4(+)CD25(+) T cells by CD8 for the functional activation of these nTregs. Suppression of allergen-induced AHR and inflammation by nTregs was abolished in mice treated with anti-CD8. Correspondingly, decreased levels of IL-10 and TGF beta and increased levels of Th2 cytokines in bronchoalveolar lavage were detected in these treated mice. Similarly, nTregs isolated from beta2m(-/-) mice or from mice treated with anti-MHC I antibody in vitro before intratracheal transfer failed to modulate AHR or inflammation. Coculture of nTregs with CD8(+) T cells increased IL-10 and TGF-beta. Addition of anti-MHC I or anti-CD8 reduced IL-10 and TGF-beta. These results demonstrate that functional activation of nTregs requires the interaction between MHC I on CD4(+)CD25(+) T cells and CD8. PMID- 17855565 TI - Water pulls the strings in hydrophobic polymer collapse. PMID- 17855566 TI - Strong coupling of predation intensity and diversity in the Phanerozoic fossil record. AB - The importance of ecological interactions in driving the evolution of animals has been the focus of intense debate among paleontologists, evolutionary biologists, and macroecologists. To test whether the intensity of such interactions covaries with the secular evolutionary trend in global biodiversity, we compiled a species level database of predation intensity, as measured by the frequency of common predation traces (drillings and repair scars ranging in age from Ediacaran to Holocene). The results indicate that the frequency of predation traces increased notably by the Ordovician, and not in the mid-Paleozoic as suggested by multiple previous studies. Importantly, these estimates of predation intensity and global diversity of marine metazoans correlate throughout the Phanerozoic fossil record regardless of corrections and methods applied. This concordance may represent (i) an ecological signal: long-term coupling of diversity and predation; (ii) a diversity-driven diffusion of predatory behaviors: an increased probability of more complex predatory strategies to appear at higher diversity levels; or (iii) a spurious concordance in signal capture: an artifact where rare species and less frequent (e.g., trace-producing) predatory behaviors are both more detectable at times when sampling improves. The coupling of predation and diversity records suggests that macroevolutionary and macroecological patterns share common causative mechanisms that may reflect either historical processes or sampling artifacts. PMID- 17855567 TI - Gamma c cytokines condition the progressive differentiation of CD4+ T cells. AB - After their initial antigen encounter in the secondary lymphoid organs, activated T cells must receive additional signals in the peripheral tissues to fully differentiate. Here, we provide evidence that gamma(c) cytokines are critical during this process. Using the Marilyn (Ml) T cell antigen receptor (TCR) transgenic model, we show that male skin grafts are tolerated in the absence of gamma(c), but that Ml CD4(+) T cells proliferate normally in response to antigen, traffic to the graft site and recruit an inflammatory response [including natural killer (NK) cells, neutrophils, and macrophages] that is independent of T cell gamma(c) expression. Whereas wild-type T cells demonstrate a progressive differentiation phenotype from the spleen to the tissues, skin-infiltrating effector T cells (CD44(hi)CD62L(lo)) from gamma(c)(-) mice were phenotypically abnormal with reduced ICOS, NKG2D, granzyme B, and IFN-gamma expression. These defects could be mapped to deficiencies in IL-2 and, surprisingly, IL-15. These results define a late checkpoint in T cell differentiation in the tissues where gamma(c) cytokines, including IL-15, authenticate CD4(+) T cell effector functions. PMID- 17855568 TI - Multiple-locus variable-number tandem-repeat analysis for rapid typing of Candida glabrata. AB - A multiple-locus variable-number tandem-repeat analysis (MLVA) using six microsatellite markers was assessed in 127 Candida glabrata isolates. Thirty seven different genotypes, stable both in vitro and in vivo, were observed. The highest discriminatory power (D = 0.902) was reached by using only four markers. MLVA seems to be relevant for C. glabrata typing. PMID- 17855569 TI - Identification of isolates within the Burkholderia cepacia complex by a multiplex recA and 16S rRNA gene real-time PCR assay. PMID- 17855570 TI - Proficiency analysis of drug susceptibility testing by national-level tuberculosis reference laboratories from 1995 to 2003. AB - A proficiency review of antituberculous drug susceptibility testing (DST) was undertaken by the regional tuberculosis reference laboratories of the Western Pacific Region of WHO to evaluate the performance of national reference laboratories (NRLs) and to ensure that the results from the participating laboratories are reliable and similar. A panel of 30 Mycobacterium tuberculosis strains with various patterns of resistance to isoniazid, rifampin, ethambutol, and streptomycin was sent to the NRLs, and their DST results were analyzed by comparing them with the judicial results. The efficiency scores for each drug were 90 to 99% (mean, 95%) for isoniazid, 77 to 100% (mean, 94%) for rifampin, 82 to 97% (mean, 90%) for ethambutol, and 82 to 98% (mean, 89%) for streptomycin. Significant changes over time in the rates of accordance with the judicial results were observed for rifampin (P < 0.0001) and streptomycin (P = 0.0002), whereas no changes were observed for ethambutol (P = 0.0880). The efficiency score for isoniazid was consistently good throughout the nine rounds. As a whole, NRL02 showed the highest score (95%) in accordance rates for all drugs, while NRL03 (86%) and NRL04 (88%) ranked lowest. Continued proficiency testing with subsequent technical assistance improved the DST quality of participating laboratories, demonstrating the importance of the current WHO/IUATLD external quality assurance program for DST proficiency testing. PMID- 17855571 TI - Rapid method for detection of influenza a and B virus antigens by use of a two photon excitation assay technique and dry-chemistry reagents. AB - New separation-free assay methods for the rapid detection of influenza A and B virus antigens are presented. The methods employ dry-chemistry reagents and the recently developed two-photon excitation (TPX) fluorescence detection technology. According to the assay scheme, virus antigens are sandwiched by capture antibody onto polymer microspheres and fluorescently labeled antibody conjugate. Consequently, fluorescent immunocomplexes are formed on the surface of microspheres in proportion to the concentration of the analyte in the sample. The fluorescence signal from individual microspheres is measured, separation free, by means of two-photon excited fluorescence detection. In order to demonstrate the applicability of the new assay technique for virus antigen detection, methods for influenza A and B viruses were constructed. The assay method for influenza A virus applied a molecular fluorescent label, whereas the method for influenza B virus required a nanoparticle fluorescent reporter to reach sufficient clinical sensitivity. The new methods utilize a dry-chemistry approach, where all assay specific reagents are dispensed into assay wells already in the manufacturing process of the test kits. The performance of the assay methods was tested with nasopharyngeal specimens using a time-resolved fluoroimmunoassay as a reference method. The results suggest that the new technique enables the rapid detection of influenza virus antigens with sensitivity and specificity comparable to that of the reference method. The dose-response curves showed linear responses with slopes equal to unity and dynamic assay ranges of 3 orders of magnitude. Applicability of the novel TPX technique for rapid multianalyte testing of respiratory infections is discussed. PMID- 17855572 TI - Novel approach for genotyping varicella-zoster virus strains from Germany. AB - In this study, we present a novel genotyping scheme to classify German wild-type varicella-zoster virus (VZV) strains and to differentiate them from the Oka vaccine strain (genotype B). This approach is based on analysis of four loci in open reading frames (ORFs) 51 to 58, encompassing a total length of 1,990 bp. The new genotyping scheme produced identical clusters in phylogenetic analyses compared to full-genome sequences from well-characterized VZV strains. Based on genotype A, D, B, and C reference strains, a dichotomous identification key (DIK) was developed and applied for VZV strains obtained from vesicle fluid and liquor samples originating from 42 patients suffering from varicella or zoster between 2003 and 2006. Sequencing of regions in ORFs 51, 52, 53, 56, 57, and 58 identified 18 single-nucleotide polymorphisms (SNPs), including two novel ones, SNP 89727 and SNP 92792 in ORF51 and ORF52, respectively. The DIK as well as phylogenetic analysis by Bayesian inference showed that 14 VZV strains belonged to genotype A, and 28 VZV strains were classified as genotype D. Neither Japanese (vaccine)-like B strains nor recombinant-like C strains were found within the samples from Germany. The novel genotyping scheme and the DIK were demonstrated to be practical and simple and allow the highly efficient replication of phylogenetic patterns in VZV initially derived from full-genome DNA sequence analyses. Therefore, this approach may allow us to draw a more comprehensive picture of wild-type VZV strains circulating in Germany and Central Europe by high-throughput procedures in the future. PMID- 17855573 TI - Multiplexed reverse transcriptase PCR assay for identification of viral respiratory pathogens at the point of care. AB - We have developed a nucleic acid-based assay that is rapid, sensitive, and specific and can be used for the simultaneous detection of five common human respiratory pathogens, including influenza virus A, influenza virus B, parainfluenza virus types 1 and 3, respiratory syncytial virus (RSV), and adenovirus groups B, C, and E. Typically, diagnosis on an unextracted clinical sample can be provided in less than 3 h, including sample collection, preparation, and processing, as well as data analysis. Such a multiplexed panel would enable rapid broad-spectrum pathogen testing on nasal swabs and therefore allow implementation of infection control measures and the timely administration of antiviral therapies. We present here a summary of the assay performance in terms of sensitivity and specificity. The limits of detection are provided for each targeted respiratory pathogen, and result comparisons were performed on clinical samples, our goal being to compare the sensitivity and specificity of the multiplexed assay to the combination of immunofluorescence and shell vial culture currently implemented at the University of California-Davis Medical Center hospital. Overall, the use of the multiplexed reverse transcription-PCR assay reduced the rate of false-negative results by 4% and reduced the rate of false-positive results by up to 10%. The assay correctly identified 99.3% of the clinical negatives and 97% of the adenovirus, 95% of the RSV, 92% of the influenza virus B, and 77% of the influenza virus A samples without any extraction performed on the clinical samples. The data also showed that extraction will be needed for parainfluenza virus, which was only identified correctly 24% of the time on unextracted samples. PMID- 17855574 TI - Molecular characterization of human immunodeficiency virus type 1 (HIV-1) and HIV 2 in Yaounde, Cameroon: evidence of major drug resistance mutations in newly diagnosed patients infected with subtypes other than subtype B. AB - Prior to current studies on the emergence of drug resistance with the introduction of antiretroviral therapy (ART) in Cameroon, we performed genotypic analysis on samples from drug-naive, human immunodeficiency virus (HIV)-infected individuals in this country. Of the 79 HIV type 1 (HIV-1) pol sequences analyzed from Cameroonian samples, 3 (3.8%) were identified as HIV-1 group O, 1 (1.2%) was identified as an HIV-2 intergroup B/A recombinant, and the remaining 75 (95.0%) were identified as HIV-1 group M. Group M isolates were further classified as subtypes A1 (n = 4), D (n = 4), F2 (n = 6), G (n = 12), H (n = 2), and K (n = 1) and as circulating recombinant forms CRF02_AG (n = 41), CRF11_cpx (n = 1), and CRF13_cpx (n = 2). Two pol sequences were identified as unique recombinant forms of CRF02_AG/F2 (n = 2). M46L (n = 2), a major resistance mutation associated with resistance to protease inhibitors, was observed in 2/75 (2.6%) group M samples. Single mutations associated with resistance to nucleoside reverse transcriptase inhibitors (T215Y/F [n = 3]) and nonnucleoside reverse transcriptase inhibitors (V108I [n = 1], L100I [n = 1], and Y181C [n = 2]) were observed in 7 of 75 (9.3%) group M samples. None of the patients had any history of ART exposure. Population surveillance of transmitted HIV drug resistance is required and should be included to aid in the development of appropriate guidelines. PMID- 17855575 TI - Effect of viral load on the outcome of herpes zoster. AB - Varicella-zoster virus (VZV) is a member of the Herpesviridae family, primary infection with which causes varicella, more commonly known as chicken pox. Characteristic of members of the alphaherpesvirus subfamily, VZV is neurotropic and establishes latency in sensory neurons. Reactivation of VZV causes herpes zoster, also known as shingles. The most frequent complication following zoster is chronic and often debilitating pain called postherpetic neuralgia (PHN), which can last for months after the disappearance of a rash. During episodes of acute zoster, VZV viremia occurs in some, but not all, patients; however, the effect of the viral load on the disease outcome is not known. Here we describe the development of a highly specific, sensitive, and reproducible real-time PCR assay to investigate the factors that may contribute to the presence and levels of baseline viremia in patients with zoster and to determine the relationship between viremia and the development and persistence of PHN. VZV DNA was detected in the peripheral blood mononuclear cells (PBMCs) of 78% of patients with acute zoster and in 9% of healthy asymptomatic blood donors. The presence of VZV in the PBMCs of patients with acute zoster was independently associated with age and being on antivirals but not with gender, immune status, extent of rash, the age of the rash at the time of blood sampling, having a history of prodromal pain, or the extent of acute pain. Prodromal pain was significantly associated with higher baseline viral loads. Viral load levels were not associated with the development or persistence of PHN at 6, 12, or 26 weeks. PMID- 17855576 TI - Antimicrobial susceptibility and genetic characteristics of Streptococcus pneumoniae isolates indicating possible nosocomial transmission routes in a community hospital in Japan. AB - A clinical study was designed to study Streptococcus pneumoniae isolates recovered from a community hospital in Japan from April 2001 to November 2002. A total of 73 isolates were defined as derived from inpatient, outpatient, and hospital staff groups. The MIC results showed that 20 strains (27.4%) were susceptible to penicillin G, 39 strains (53.4%) had intermediate resistance, and 14 strains (19.2%) had full resistance. Low susceptibility to macrolides was also detected: 32.9%, 32.9%, and 34.2% of all strains were resistant to erythromycin, clarithromycin, and azithromycin, respectively. Thirty strains (41%) were resistant to at least two different kinds of antibiotics. Nineteen disparate serotypes were detected besides two nontypeable strains, and the predominant serotypes were 19F and 23F. Pulsed-field gel electrophoresis (PFGE) pattern A was dominant in the serotype 19F group; this pattern was similar to that of the international clone Taiwan 19F. A total of 10 different patterns were detected in the 23F group and were distinguishable from those of the international clones Spain 23F and Taiwan 23F. Pattern b strains were identified in the same ward, and pattern d strains were found both in patients with nosocomial pneumococcal infections (NPI) and in outpatients. In conclusion, drug-resistant S. pneumoniae was spreading rapidly, especially isolates of the serotype 19F and 23F groups. PFGE data revealed interpatient transmission and suggested that there might be some association between NPI patient strains and outpatient strains. PMID- 17855577 TI - Evaluation of MChip with historic subtype H1N1 influenza A viruses, including the 1918 "Spanish Flu" strain. AB - The robustness of a recently developed diagnostic microarray for influenza, the MChip, was evaluated with 16 historic subtype H1N1 influenza A viruses (A/H1N1), including A/Brevig Mission/1/1918. The matrix gene segments from all 16 viruses were successfully detected on the array. An artificial neural network trained with temporally related A/H1N1 viruses identified A/Brevig Mission/1/1918 as influenza virus A/H1N1 with 94% probability. PMID- 17855578 TI - Monitoring of polyomavirus BK virus viruria and viremia in renal allograft recipients by use of a quantitative real-time PCR assay: one-year prospective study. AB - We have developed a real-time quantitative PCR (rt-QPCR) assay to detect and kinetically monitor BK virus viruria and viremia in renal transplant recipients (RTRs). A total of 607 urine and 223 plasma samples were collected from 203 individuals including those with BK virus-associated nephropathy (BKVAN) (n = 8), those undergoing routine posttransplant surveillance (SV) (n = 155), those with nontransplant chronic kidney disease (NT-CKD) (n = 20), and healthy living kidney donors (LD) (n = 20). The rt-QPCR assay was found to be highly sensitive and specific, with a wide dynamic range (2.4 to 11 log(10) copies/ml) and very good precision (coefficient of variation, approximately 5.9%). There was a significant difference in the prevalences of viruria and viremia between the BKVAN (100% and 100%) and SV (23% and 3.9%) groups (P < 0.001). No viruria or viremia was detected in LD or in NT-CKD patients. The median (range) peak levels of BK virus viruria and viremia, in log(10) copies/ml, were 10.26 (9.04 to 10.83) and 4.83 (3.65 to 5.86) for the BKVAN group versus 0 (0 to 10.83) and 0 (0 to 5.65) for the SV group, respectively (P < 0.001). When the BK virus load in the urine was <7.0 log(10) copies/ml, no BK virus viremia was detected. When the BK virus load in the urine reached 7.0, 8.0, 9.0, and > or =10.0 log(10) copies/ml, the corresponding detection of BK virus viremia increased to 20, 33, 50, and 100%, respectively. We propose monitoring of BK virus viruria in RTRs, with plasma BK virus load testing reserved for those with viruria levels of > or =7.0 log(10) copies/ml. PMID- 17855579 TI - Concordance between Neisseria gonorrhoeae genotypes recovered from known sexual contacts. AB - Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) is a highly discriminatory molecular typing procedure that provides precise and unambiguous strain characterization. Since molecular typing can complement contact tracing for reconstructing gonorrhea sexual networks, the concordance between the NG-MAST genotypes of pairs of N. gonorrhoeae isolates from recent sexual contacts was examined. Among 72 pairs of gonococci from recent sexual contacts, the genotypes of each pair were concordant in 65 cases (90.3%). In two further pairs, the isolates from sexual contacts differed by only a single nonsynonymous substitution in the porin gene, and in both of these pairs, the isolates were the same by opa typing. The other five nonconcordant pairs of isolates were clearly different strains. opa typing data were available for 51 of the pairs of isolates from sexual contacts, and concordant opa types were obtained in 38 cases (74.5%). NG-MAST should therefore be better than opa typing at identifying recent sexual contacts and has the important advantage over opa typing of being a more precise method of strain characterization. PMID- 17855580 TI - Noise-induced transition to bursting in responses of paddlefish electroreceptor afferents. AB - The response properties of ampullary electroreceptors of paddlefish, Polyodon spathula, were studied in vivo, as single-unit afferent responses to external electrical stimulation with varied intensities of several types of noise waveforms, all Gaussian and zero-mean. They included broadband white noise, Ornstein-Uhlenbeck noise, low- or high-frequency band-limited noise, or natural noise recorded from swarms of Daphnia zooplankton prey, or from individual prey. Normally the afferents fire spontaneously in a tonic manner, which is actually quasiperiodic due to embedded oscillators. 1) Weak noise stimuli increased the variability of afferent firing, but it remained tonic. 2) In contrast, stimulation with less-weak broadband noise led to a qualitative change of the firing patterns, to parabolic bursting, even though the mean firing rate was scarcely affected. 3) The transition to afferent bursting was marked by the development of two well-separated timescales: the fast frequency of spiking inside bursts at 20 kHz) in cat AI. Second, the extent of spectral integration covaries with the local tonotopic gradient in the low- and mid-frequency ranges. Regions with a shallow frequency gradient tend to have narrower spectral integration than those with a steep gradient. These relationships between spectral selectivity and frequency gradient constrain forebrain models of thalamo- and corticocortical convergence and connectivity and may reflect the processing of behaviorally relevant stimulus constellations. PMID- 17855588 TI - Manipulation of the potassium channel Kv1.1 and its effect on neuronal excitability in rat sensory neurons. AB - Potassium channels play a critical role in regulating many aspects of action potential (AP) firing. To establish the contribution of the voltage-dependent potassium channel Kv1.1 in regulating excitability, we used the selective blocker dendrotoxin-K (DTX-K) and small interfering RNA (siRNA) targeted to Kv1.1 to determine their effects on AP firing in small-diameter capsaicin-sensitive sensory neurons. A 5-min exposure to 10 nM DTX-K suppressed the total potassium current (I(K)) measured at +40 mV by about 33%. DTX-K produced a twofold increase in the number of APs evoked by a ramp of depolarizing current. Associated with increased firing was a decrease in firing threshold and rheobase. DTX-K did not alter the resting membrane potential or the AP duration. A 48-h treatment with siRNA targeted to Kv1.1 reduced the expression of this channel protein by about 60% as measured in Western blots. After treatment with siRNA, I(K) was no longer sensitive to DTX-K, indicating a loss of functional protein. Similarly, after siRNA treatment exposure to DTX-K had no effect on the number of evoked APs, firing threshold, or rheobase. However, after siRNA treatment, the firing threshold had values similar to those obtained after acute exposure to DTX-K, suggesting that the loss of Kv1.1 plays a critical role in setting this parameter of excitability. These results demonstrate that Kv1.1 plays an important role in limiting AP firing and that siRNA may be a useful approach to establish the role of specific ion channels in the absence of selective antagonists. PMID- 17855589 TI - Developmental changes in agonist-induced retrograde signaling at parallel fiber Purkinje cell synapses: role of calcium-induced calcium release. AB - In cerebellar Purkinje cells (PCs), activation of postsynaptic mGluR1 receptors inhibits parallel fiber (PF) to PC synaptic transmission by retrograde signaling. However, results were conflicting with respect to whether endocannabinoids or glutamate (Glu) is the retrograde messenger involved. Experiments in cerebellar slices from 10- to 12-day-old rats and mice confirmed that suppression of PF excitatory postsynaptic currents (EPSCs) by mGluR1 agonists was entirely blocked by cannabinoid receptor antagonists at this early developmental stage. In contrast, suppression of PF-EPSCs by mGluR1 agonists was only partly blocked by cannabinoid receptor antagonists in 18- to 22-day-old rats, and the remaining suppression was accompanied by an increase in paired-pulse facilitation. This endocannnabinoidindependent suppression of PF-EPSCs was potentiated by the Glu uptake inhibitor D-threo-beta-benzyloxyaspartate (D-TBOA) and blocked by the desensitizing kainate (KA) receptors agonist SYM 2081, by nonsaturating concentrations of 6-cyano-7-nitroquinoxaline-2-3-dione (CNQX) [but not by GYKI 52466 hydrochloride (GYKI)] and by dialyzing PCs with guanosine 5'-[beta thio]diphosphate (GDP-betaS). An endocannnabinoid-independent suppression of PF EPSCs was also present in nearly mature wild-type mice but was absent in GluR6(-/ ) mice. The endocannnabinoid-independent suppression of PF-EPSCs induced by mGluR1 agonists and the KA-dependent component of depolarization-induced suppression of excitation (DSE) were blocked by ryanodine acting at a presynaptic level. We conclude that retrograde release of Glu by PCs participates in mGluR1 agonist-induced suppression of PF-EPSCs at nearly mature PF-PC synapses and that Glu operates through activation of presynaptic KA receptors located on PFs and prolonged release of calcium from presynaptic internal calcium stores. PMID- 17855590 TI - Gap junctions are required for NMDA receptor dependent cell death in developing neurons. AB - A number of studies have indicated an important role for N-methyl-D-aspartate (NMDA) receptors in cell survival versus cell death decisions during neuronal development, trauma, and ischemia. Coupling of neurons by electrical synapses (gap junctions) is high or increases in neuronal networks during all three of these conditions. However, whether neuronal gap junctions contribute to NMDA receptor-regulated cell death is not known. Here we address the role of neuronal gap junction coupling in NMDA receptor-regulated cell death in developing neurons. We report that inactivation or hyperactivation of NMDA receptors induces neuronal cell death in primary hypothalamic cultures, specifically during the peak of developmental gap junction coupling. In contrast, increasing or decreasing NMDA receptor function when gap junction coupling is low has no or greatly reduced impact on cell survival. Pharmacological inactivation of gap junctions or knockout of neuronal connexin 36 prevents the cell death caused by NMDA receptor hypofunction or hyperfunction. The results indicate the critical role of neuronal gap junctions in cell death caused by increased or decreased NMDA receptor function in developing neurons. Based on these data, we propose the novel hypothesis that NMDA receptors and gap junctions work in concert to regulate neuronal survival. PMID- 17855591 TI - Alterations in GABA(A) receptor mediated inhibition in adjacent dorsal midline thalamic nuclei in a rat model of chronic limbic epilepsy. AB - There is evidence that the dorsal midline thalamus is involved in the seizures of limbic epilepsy. However, little is known about the inhibitory synaptic function in this region. In the present study, inhibitory postsynaptic currents (IPSCs) mediated by GABA(A) receptors were recorded from the mediodorsal (MD) and paraventricular (PV) nuclei from control and epileptic animals. In the MD, the spontaneous (s)IPSCs for epileptic animals had a lower frequency, prolonged rise time, prolonged decay, but unaltered net charge transfer compared with controls. The miniature (m)IPSC parameters were unaltered in the epileptic animals. In contrast, in the PV, both sIPSCs and mIPSCs in the epileptic animals were more frequent with larger amplitudes and there was an increase in the net charge transfer compared with controls. The rise times of the sIPSCs of the PV neurons were significantly prolonged, whereas the weighted decay time of the mIPSC was significantly shortened in epileptic animals. These findings suggest that the changes associated with inhibitory synaptic transmission in limbic epilepsy are not uniform across regions in the thalamus that are part of the seizure circuit. PMID- 17855592 TI - Spatial selectivity to intracochlear electrical stimulation in the inferior colliculus is degraded after long-term deafness in cats. AB - In an animal model of electrical hearing in prelingually deaf adults, this study examined the effects of deafness duration on response thresholds and spatial selectivity (i.e., cochleotopic organization, spatial tuning and dynamic range) in the central auditory system to intracochlear electrical stimulation. Electrically evoked auditory brain stem response (EABR) thresholds and neural response thresholds in the external (ICX) and central (ICC) nuclei of the inferior colliculus were estimated in cats after varying durations of neonatally induced deafness: in animals deafened <1.5 yr (short-deafened unstimulated, SDU cats) with a mean spiral ganglion cell (SGC) density of approximately 45% of normal and in animals deafened >2.5 yr (long-deafened, LD cats) with severe cochlear pathology (mean SGC density <7% of normal). LD animals were subdivided into unstimulated cats and those that received chronic intracochlear electrical stimulation via a feline cochlear implant. Acutely deafened, implanted adult cats served as controls. Independent of their stimulation history, LD animals had significantly higher EABR and ICC thresholds than SDU and control animals. Moreover, the spread of electrical excitation was significantly broader and the dynamic range significantly reduced in LD animals. Despite the prolonged durations of deafness the fundamental cochleotopic organization was maintained in both the ICX and the ICC of LD animals. There was no difference between SDU and control cats in any of the response properties tested. These findings suggest that long-term auditory deprivation results in a significant and possibly irreversible degradation of response thresholds and spatial selectivity to intracochlear electrical stimulation in the auditory midbrain. PMID- 17855594 TI - Direct effect of human immunodeficiency virus protease inhibitors on neutrophil function and apoptosis via calpain inhibition. AB - Impairment of neutrophil functions and high levels of apoptotic neutrophils have been reported in human immunodeficiency virus (HIV) patients. The aim of the present study was to investigate the direct in vitro effects of the different HIV protease inhibitors (PIs) on neutrophil functions and apoptosis and to explore their mechanisms of action. The effects of nelfinavir (NFV), saquinavir (SQV), lopinavir (LPV), ritonavir (RTV), and amprenavir (APV) in the range of 5 to 100 microg/ml on neutrophil function, apoptosis, and mu-calpain activity were studied. The neutrophil functions studied included superoxide production stimulated by 5 ng/ml phorbol myristate acetate, 5 x 10(-7) M N-formyl-methionyl leucyl-phenylalanine, and 1 mg/ml opsonized zymosan; specific chemotaxis; random migration; and phagocytosis. Apoptosis was determined by DNA fragmentation, fluorescein isothiocyanate-annexin V binding, and nuclear morphology. All three neutrophil functions, as well as apoptosis, were similarly affected by the PIs. SQV and NFV caused marked inhibition and LPV and RTV caused moderate inhibition, while APV had a minor effect. mu-Calpain activity was not affected by the PIs in neutrophil lysate but was inhibited after its translocation to the membranes after cell stimulation. SQV, which was the most potent inhibitor of neutrophil functions and apoptosis, caused significant inhibition of calpain activity, while APV had no effect. The similar patterns of inhibition of neutrophil functions and apoptosis by the PIs, which coincided with inhibition of calpain activity, suggest the involvement of calpain activity in the regulation of these processes. PMID- 17855595 TI - Targeting Cre recombinase to specific neuron populations with bacterial artificial chromosome constructs. PMID- 17855596 TI - A molecular switch for induction of long-term depression of corticostriatal transmission. PMID- 17855597 TI - A knock-in reporter model of Batten disease. AB - Juvenile neuronal ceroid lipofuscinosis is a severe inherited neurodegenerative disease resulting from mutations in CLN3 (ceroid-lipofuscinosis, neuronal 3, juvenile). CLN3 function, and where and when it is expressed during development, is not known. In this study, we generated a knock-in reporter mouse to elucidate CLN3 expression during embryogenesis and after birth and to correlate expression and behavior in a CLN3-deficient mouse. In embryonic brain, expression appeared in the cortical plate. In postnatal brain, expression was prominent in the cortex, subiculum, parasubiculum, granule neurons of the dentate gyrus, and some brainstem nuclei. In adult brain, reporter gene expression waned in most areas but remained in vascular endothelia and the dentate gyrus. Mice homozygous for Cln3 deletion showed two hallmark pathological features of the neuronal ceroid lipofuscinosises: autofluorescent inclusions and lysosomal enzyme elevation. Moreover, CLN3-deficient reporter mice displayed progressive neurological deficits, including impaired motor function, decreased overall activity, acquisition of resting tremors, and increased susceptibility to pentilentetrazole induced seizures. Notably, seizure induction in heterozygous mice was accompanied by enhanced reporter expression. This model provides us with the unique ability to correlate expression with pathology and behavior, thus facilitating the elucidation of CLN3 function and the pathogenesis of Batten disease. PMID- 17855598 TI - Developmental switch in the contribution of presynaptic and postsynaptic NMDA receptors to long-term depression. AB - NMDA receptor (NMDAR) activation is required for many forms of learning and memory as well as sensory system receptive field plasticity, yet the relative contribution of presynaptic and postsynaptic NMDARs over cortical development remains unknown. Here we demonstrate a rapid developmental loss of functional presynaptic NMDARs in the neocortex. Presynaptic NMDARs enhance neurotransmitter release at synapses onto visual cortex pyramidal cells in young mice [before postnatal day 20 (P20)], but they have no apparent effect after the onset of the critical period for receptive field plasticity (>P23). Immunoelectron microscopy revealed that the loss of presynaptic NMDAR function is likely attributable in part to a 50% reduction in the prevalence of presynaptic NMDARs. Coincident with the observed loss of presynaptic NMDAR function, there is an abrupt change in the mechanisms of timing-dependent long-term depression (tLTD). Induction of tLTD before the onset of the critical period requires activation of presynaptic but not postsynaptic NMDARs, whereas the induction of tLTD in older mice requires activation of postsynaptic NMDARs. By demonstrating that both presynaptic and postsynaptic NMDARs contribute to the induction of synaptic plasticity and that their relative roles shift over development, our findings define a novel, and perhaps general, property of synaptic plasticity in emerging cortical circuits. PMID- 17855599 TI - Vesicle pool heterogeneity at hippocampal glutamate and GABA synapses. AB - Glutamate and GABA are the major fast excitatory and inhibitory neurotransmitters, respectively, in the CNS. Although glutamate and GABA have clearly distinct postsynaptic actions, we are just beginning to appreciate that presynaptic differences between glutamatergic and GABAergic neurons may contribute to distinct functions of these transmitter systems. We therefore probed possible differences between the functional synaptic vesicle populations of glutamatergic and GABAergic neurons. We examined superecliptic synaptopHluorin (SpH) fluorescence during 20 Hz electrical stimulation in transfected hippocampal neurons and identified the phenotype of SpH-fluorescent synapses with post hoc immunostaining. With 200 stimuli (10 s), individual glutamate synapses displayed considerably more variability in peak SpH fluorescence than GABA synapses, without a strong difference in the mean SpH fluorescence increase. This spatial heterogeneity could not be accounted for by differences in endocytosis, which was nearly constant over these short time periods across glutamate and GABA synapses. Instead, variability in vesicle exocytosis correlated with variability in total vesicle staining and in measures of the total recycling pool size. Differences were also evident using FM1-43 [N-(3-triethylammoniumpropyl)-4-(4 (dibutylamino)styryl) pyridinium dibromide] uptake. These data support the idea that the population of glutamate synapses exhibits more heterogeneity in release properties than the population of GABA synapses, possibly correlated with glutamatergic synaptic malleability. PMID- 17855600 TI - Reduced expression of A-type potassium channels in primary sensory neurons induces mechanical hypersensitivity. AB - A-type K+ channels (A-channels) are crucial in controlling neuronal excitability, and their downregulation in pain-sensing neurons may increase pain sensation. To test this hypothesis, we first characterized the expression of two A-channels, Kv3.4 and Kv4.3, in rat dorsal root ganglion (DRG) neurons. Kv3.4 was expressed mainly in the nociceptive DRG neurons, in their somata, axons, and nerve terminals innervating the dorsal horn of spinal cord. In contrast, Kv4.3 appeared selectively in the somata of a subset of nonpeptidergic nociceptive DRG neurons. Most Kv4.3(+) DRG neurons also expressed Kv3.4. In a neuropathic pain model induced by spinal nerve ligation in rats, the protein levels of Kv3.4 and Kv4.3 in the DRG neurons were greatly reduced. After Kv3.4 or Kv4.3 expression in lumbar DRG neurons was suppressed by intrathecal injections of antisense oligodeoxynucleotides, mechanical but not thermal hypersensitivity developed. Together, our data suggest that reduced expression of A-channels in pain-sensing neurons may induce mechanical hypersensitivity, a major symptom of neuropathic pain. PMID- 17855601 TI - Perturbed chloride homeostasis and GABAergic signaling in human temporal lobe epilepsy. AB - Changes in chloride (Cl-) homeostasis may be involved in the generation of some epileptic activities. In this study, we asked whether Cl- homeostasis, and thus GABAergic signaling, is altered in tissue from patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis. Slices prepared from this human tissue generated a spontaneous interictal-like activity that was initiated in the subiculum. Records from a minority of subicular pyramidal cells revealed depolarizing GABA(A) receptor-mediated postsynaptic events, indicating a perturbed Cl- homeostasis. We assessed possible contributions of changes in expression of the potassium-chloride cotransporter KCC2. Double in situ hybridization showed that mRNA for KCC2 was absent from approximately 30% of CaMKIIalpha (calcium/calmodulin-dependent protein kinase IIalpha)-positive subicular pyramidal cells. Combining intracellular recordings with biocytin filled electrodes and KCC2 immunochemistry, we observed that all cells that were hyperpolarized during interictal events were immunopositive for KCC2, whereas the majority of depolarized cells were immunonegative. Bumetanide, at doses that selectively block the chloride-importing potassium-sodium-chloride cotransporter NKCC1, produced a hyperpolarizing shift in GABA(A) reversal potentials and suppressed interictal activity. Changes in Cl- transporter expression thus contribute to human epileptiform activity, and molecules acting on these transporters may be useful antiepileptic drugs. PMID- 17855602 TI - Bimodal action of menthol on the transient receptor potential channel TRPA1. AB - TRPA1 is a calcium-permeable nonselective cation transient receptor potential (TRP) channel that functions as an excitatory ionotropic receptor in nociceptive neurons. TRPA1 is robustly activated by pungent substances in mustard oil, cinnamon, and garlic and mediates the inflammatory actions of environmental irritants and proalgesic agents. Here, we demonstrate a bimodal sensitivity of TRPA1 to menthol, a widely used cooling agent and known activator of the related cold receptor TRPM8. In whole-cell and single-channel recordings of heterologously expressed TRPA1, submicromolar to low-micromolar concentrations of menthol cause channel activation, whereas higher concentrations lead to a reversible channel block. In addition, we provide evidence for TRPA1-mediated menthol responses in mustard oil-sensitive trigeminal ganglion neurons. Our data indicate that TRPA1 is a highly sensitive menthol receptor that very likely contributes to the diverse psychophysical sensations after topical application of menthol to the skin or mucous membranes of the oral and nasal cavities. PMID- 17855603 TI - Induction and survival of binucleated Purkinje neurons by selective damage and aging. AB - Fusion of bone marrow-derived cells with adult Purkinje cells in the cerebellum gives rise to binucleated Purkinje cells. Whether fusion can be modulated by epigenetic factors and whether fused neurons are stable has remained unclear. Here, we show that in mice and rats, partial ablation of Purkinje cells and local microglial activation in the absence of structural damage to the cerebellum increase the rate of fusion. Moreover, mouse Purkinje cells once fused with bone marrow-derived cells are viable for at least 7 months. We also show that cerebellar irradiation is unnecessary for the generation of binucleated Purkinje cells after bone marrow grafting. Moreover, binucleated Purkinje cells can be found in aged mice that did not receive any treatment, suggesting that fusion events occasionally occur throughout the whole lifespan of healthy, unmanipulated individuals. However, in aged chimeric mice that, after bone marrow transplant, have the majority of their nucleated blood cells fluorescent, the number of binucleated fluorescent Purkinje cells is two orders of magnitude less than the total number of binucleated Purkinje cells. This suggests that, in the majority of heterokaryons, either the incoming nucleus is quickly inactivated or fusion is not the only way to generate a binucleated Purkinje cell. PMID- 17855604 TI - Common and differential ventrolateral prefrontal activity during inhibition of hand and eye movements. AB - The inferior frontal cortex, particularly the ventrolateral prefrontal cortex (VLPFC) in the right hemisphere, has been implicated to serve as a general inhibitory mechanism in the cognitive control of behavior. Because this notion was primarily based on studies of response inhibition in manual tasks, it has yet to be validated in other response modalities. We conducted a functional magnetic resonance imaging study to examine whether the VLPFC is commonly activated during inhibition of responses by hand and by eye within the same subjects. We used the stop-signal task, a relatively pure measure of response inhibition, as the behavioral paradigm. Results from 12 subjects showed that both the right and the left caudal VLPFC and anterior insula, rostral to the premotor area, are activated during inhibition of both manual and saccadic responses. Within the posterior VLPFC, activations overlapped to a significant extent across the two response modalities, although a weaker functionally differentiation was also found along the dorsoventral axis. Other areas such as medial superior frontal gyrus (pre-supplementary motor area/supplementary eye field), dorsolateral prefrontal cortex, and inferior parietal cortex were also activated during canceling both hand and eye movements. Our findings suggest that a common VLPFC network is involved in response inhibition, although the specific control of the different response modalities may be partially segregated within the lateral prefrontal cortex. PMID- 17855605 TI - PDZ protein interactions underlying NMDA receptor-mediated excitotoxicity and neuroprotection by PSD-95 inhibitors. AB - In neuronal synapses, PDZ domains [postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1] of PSD-95 proteins interact with C termini of NMDA receptor [NMDAR (NR)] subunits, linking them to downstream neurotoxic signaling molecules. Perturbing NMDAR/PSD-95 interactions with a Tat peptide comprising the nine C-terminal residues of the NR2B subunit (Tat-NR2B9c) reduces neurons' vulnerability to excitotoxicity and ischemia. However, NR subunit C termini may bind many of >240 cellular PDZs, any of which could mediate neurotoxic signaling independently of PSD-95. Here, we performed a proteomic and biochemical analysis of the interactions of all known human PDZs with synaptic signaling proteins including NR1, NR2A-NR2D, and neuronal nitric oxide synthase (nNOS). Tat-NR2B9c, whose interactions define PDZs involved in neurotoxic signaling, was also used. NR2A-NR2D subunits and Tat-NR2B9c had similar, highly specific, PDZ protein interactions, of which the strongest were with the PSD-95 family members (PSD-95, PSD-93, SAP97, and SAP102) and Tax interaction protein 1 (TIP1). The PSD-95 PDZ2 domain bound NR2A-NR2C subunits most strongly (EC50, approximately 1 microM), and fusing the NR2B C terminus to Tat enhanced its affinity for PSD-95 PDZ2 by >100 fold (EC50, approximately 7 nM). IC50 values for Tat-NR2B9c inhibiting NR2A NR2C/PSD-95 interactions (approximately 1-10 microM) and nNOS/PSD-95 interactions (200 nM) confirmed the feasibility of such inhibition. To determine which of the PDZ interactions of Tat-NR2B9c mediate neuroprotection, one of PSD-95, PSD-93, SAP97, SAP102, TIP1, or nNOS expression was inhibited in cortical neurons exposed to NMDA toxicity. Only neurons lacking PSD-95 or nNOS but not PSD-93, SAP97, SAP102, or TIP1 exhibited reduced excitotoxic vulnerability. Thus, despite the ubiquitousness of PDZ domain-containing proteins, PSD-95 and nNOS above any other PDZ proteins are keys in effecting NMDAR-dependent excitotoxicity. Consequently, PSD-95 inhibition may constitute a highly specific strategy for treating excitotoxic disorders. PMID- 17855606 TI - Swimming against the tide: mobility of the microtubule-associated protein tau in neurons. AB - Long-haul transport along microtubules is crucial for neuronal polarity, and transport defects cause neurodegeneration. Tau protein stabilizes microtubule tracks, but in Alzheimer's disease it aggregates and becomes missorted into the somatodendritic compartment. Tau can inhibit axonal transport by obstructing motors on microtubules, yet tau itself can still move into axons. We therefore investigated tau movement by live-cell fluorescence microscopy, FRAP (fluorescence recovery after photobleaching), and FSM (fluorescence speckle microscopy). Tau is highly dynamic, with diffusion coefficients of approximately 3 microm2/s and microtubule dwell times of approximately 4 s. This facilitates the entry of tau into axons over distances of millimeters and periods of days. For longer distances and times, two mechanisms of tau transport are observed. At low near-physiological levels, tau is cotransported with microtubule fragments from cell bodies into axons, moving at instantaneous velocities approximately 1 microm/s. At high concentrations, tau forms local accumulations moving bidirectionally at approximately 0.3 microm/s. These clusters first appear at distal endings of axons and may indicate an early stage of neurite degeneration. PMID- 17855607 TI - A single injection of an adeno-associated virus vector into nuclei with divergent connections results in widespread vector distribution in the brain and global correction of a neurogenetic disease. AB - Neurogenetic disorders typically affect cells throughout the brain. Adeno associated virus (AAV) vector-mediated transfer of a normal cDNA can correct the metabolic defects at the site of injection, but treatment of the entire brain requires widespread delivery of the normal gene and/or protein. Current methods require multiple injections for widespread distribution. However, some AAV vectors can be transported along neuronal pathways associated with the injected region. Thus, targeting widely dispersed systems in the CNS might be a pathway for gene dispersal from a limited number of sites. We tested this hypothesis in the ventral tegmental area (VTA), a region with numerous efferent and afferent projections. A single 1 mul injection resulted in transport of the vector genome to projection sites in distal parts of the brain. When compared with injections into the striatum, the VTA injection resulted in higher enzyme levels in more regions of the brain. The AAV-9 serotype vector was the most widely disseminated, but AAV-Rh.10 and AAV-1 were also transported after VTA injection. The effect on global lesions of a neurogenetic disease was tested in the mouse model of MPS VII (mucopolysaccharidosis VII), a lysosomal storage disorder. Widespread distribution of the vector genome after AAV-9 VTA injection resulted in even further distribution of the enzyme product, by secretion and uptake by surrounding cells, and complete correction of the storage lesions throughout the entire brain. This unprecedented level of correction from a single injection into the developed brain provides a potential strategy to correct a large volume of brain while minimizing the number of injections. PMID- 17855608 TI - Caveolin proteins are essential for distinct effects of membrane estrogen receptors in neurons. AB - It has become widely accepted that along with its ability to directly regulate gene expression, estradiol also influences cell signaling and brain function via rapid membrane-initiated events. Many of these novel signaling processes are dependent on estrogen receptors (ERs) localized to the neuronal membrane. However, the mechanism(s) by which ERs are able to trigger cell signaling when targeted to the neuronal membrane surface has yet to be determined. In hippocampal neurons, we find that caveolin proteins are essential for the regulation of CREB (cAMP response element-binding protein) phosphorylation after estradiol activation of metabotropic glutamate receptor (mGluR) signaling. Furthermore, caveolin-1 (CAV1) and CAV3 differentially regulate the ability of estradiol to activate two discrete signaling pathways. ER alpha activation of mGluR1a is dependent on CAV1, whereas CAV3 is necessary for ER alpha and ER beta activation of mGluR2/3. These results are consistent with previous reports in non neuronal cells, implicating the importance of caveolin proteins in rapid estrogen signaling. In addition, the functional isolation of distinct estrogen-sensitive signaling pathways by different caveolin proteins suggests novel mechanisms through which the membrane-initiated effects of estradiol are orchestrated. PMID- 17855609 TI - Synaptic integration of adult-generated olfactory bulb granule cells: basal axodendritic centrifugal input precedes apical dendrodendritic local circuits. AB - The adult mammalian olfactory bulb (OB) receives a continuing influx of new interneurons. Neuroblasts from the subventricular zone (SVZ) migrate into the OB and differentiate into granule cells and periglomerular cells that are presumed to integrate into the synaptic circuits of the OB. We have used retroviral infection into the SVZ of mice to label adult-generated granule cells and follow their differentiation and integration into OB circuitry. Using synaptic markers and electron microscopy, we show new granule cells integrating into the reciprocal circuitry of the external plexiform layer (EPL), beginning at 21 d postinfection (dpi). We further show that synapses are formed earlier, beginning at 10 dpi, on the somata and basal dendrites of new cells in the granule cell layer (GCL), before dendritic elaboration in the EPL. In the EPL, elaborate dendritic arbors with spines are first evident at 14 dpi. The density of spines increases from 14 to 28 dpi, and then decreases by 56 dpi. Despite the initial appearance of dendritic spines at 14 dpi in the EPL, no expression of presynaptic or postsynaptic markers is seen until 21 dpi. These data suggest that adult generated granule cells are first innervated by centrifugal or mitral/tufted cell axon collaterals in the GCL and that these inputs may contribute to their differentiation, maturation, and synaptic integration into the dendrodendritic local circuits found in the EPL. PMID- 17855610 TI - Properties of persistent postnatal cortical subplate neurons. AB - Subplate (SP) neurons are important for the proper development of thalamocortical innervation. They are necessary for formation of ocular dominance and orientation columns in visual cortex. During the perinatal period, many SP neurons die. The surviving cohort forms interstitial cells in the white matter (WM) and a band of horizontally oriented cells below layer VI (layer VIb, layer VII, or subplate cells). Although the function of embryonic SP neurons has been well established, the functional roles of WM and postnatal SP cells are not known. We used a combination of anatomical, immunohistochemical, and electrophysiological techniques to explore the dendritic morphology, neurotransmitter phenotype, intrinsic electrophysiological, and synaptic input properties of these surviving cells in the rat visual cortex. The density of SP and WM cells significantly decreases during the first month of life. Both populations express neuronal markers and have extensive dendritic arborizations within the SP, WM, and to the overlying visual cortex. Some intrinsic electrophysiological properties of SP and WM cells are similar: each generates high-frequency slowly adapting trains of action potentials in response to a sustained depolarization. However, SP cells exhibit greater frequency-dependent action potential broadening than WM neurons. Both cell types receive predominantly AMPA/kainate receptor-mediated excitatory synaptic input that undergoes paired-pulse facilitation as well as NMDA receptor and GABAergic input. Synaptic inputs to these cells can also undergo long-term synaptic plasticity. Thus, surviving SP and WM cells are functional electrogenic neurons integrated within the postnatal visual cortical circuit. PMID- 17855611 TI - Motor force field learning influences visual processing of target motion. AB - There are reciprocal connections between visual and motor areas of the cerebral cortex. Although recent studies have provided intriguing new insights, in comparison with volume of research on the visual control of movement, relatively little is known about how movement influences vision. The motor system is perfectly suited to learn about environmental forces. Does environmental force information, learned by the motor system, influence visual processing? Here, we show that learning to compensate for a force applied to the hand influenced how participants predicted target motion for interception. Ss trained in one of three constant force fields by making reaching movements while holding a robotic manipulandum. The robot applied forces in a null [null force field (NFF)], leftward [leftward force field (LFF)], or [rightward force field (RFF)] direction. Training was followed immediately with an interception task. The target accelerated from left to right and Ss's task was to stab it. When viewing time was optimal for prediction, the RFF group initiated their responses earlier and hit more targets, and the LFF group initiated their responses later and hit fewer targets, than the NFF group. In follow-up experiments, we show that motor learning is necessary, and we rule out the possibility that explicit force direction information drives how Ss altered their predictions of visual motion. Environmental force information, acquired by motor learning, influenced how the motion of nearby visual targets was predicted. PMID- 17855612 TI - Orbitofrontal cortex encodes willingness to pay in everyday economic transactions. AB - An essential component of every economic transaction is a willingness-to-pay (WTP) computation in which buyers calculate the maximum amount of financial resources that they are willing to give up in exchange for the object being sold. Despite its pervasiveness, little is known about how the brain makes this computation. We investigated the neural basis of the WTP computation by scanning hungry subjects' brains using functional magnetic resonance imaging while they placed real bids for the right to eat different foods. We found that activity in the medial orbitofrontal cortex and in the dorsolateral prefrontal cortex encodes subjects' WTP for the items. Our results support the hypothesis that the medial orbitofrontal cortex encodes the value of goals in decision making. PMID- 17855613 TI - Coincident activation of metabotropic glutamate receptors and NMDA receptors (NMDARs) downregulates perisynaptic/extrasynaptic NMDARs and enhances high fidelity neurotransmission at the developing calyx of Held synapse. AB - NMDA receptors (NMDARs) are usually downregulated in developing central synapses, but underlying mechanisms and functional consequences are not well established. Using developing calyx of Held synapses in the mouse auditory brainstem, we show here that pairing presynaptic stimulation with postsynaptic depolarization results in a persistent downregulation in the summated amplitude of NMDAR mediated EPSCs (NMDAR-EPSCs) during a train of stimuli (100/200 Hz, 100 ms) at both 22 degrees C and 35 degrees C. In contrast, the amplitude of single NMDAR EPSCs or AMPA receptor-mediated EPSCs in the same synapses is not significantly altered, implying a preferential downregulation of perisynaptic/extrasynaptic NMDARs. Induction of this downregulation is blocked by antagonists for NMDARs or group I metabotropic glutamate receptors (mGluRs), suggesting that coincident activation of these two receptors is required. When the postsynaptic neuron is loaded with the fast Ca2+ buffer BAPTA or depolarized to +60 mV to reduce the driving force for Ca2+ influx, downregulation of the summated NMDAR-EPSCs is abolished, indicating Ca2+ plays a critical role in the induction. The expression of this downregulation depends on ongoing synaptic activity, and is attenuated by a dynamin peptide (D15) that blocks clathrin-dependent internalization. We further demonstrated that the same induction paradigm specifically reduces NMDAR dependent plateau potential and aberrant spike firings during repetitive activity. Together, our results suggest that coincident activation of mGluRs and NMDARs during intense synaptic activity may lead to selective endocytosis of NMDARs in the perisynaptic/extrasynaptic domain, and implicate that mGluRs are potentially important for gating development of high-fidelity neurotransmission at this synapse. PMID- 17855614 TI - Decreased central mu-opioid receptor availability in fibromyalgia. AB - The underlying neurophysiology of acute pain is fairly well characterized, whereas the central mechanisms operative in chronic pain states are less well understood. Fibromyalgia (FM), a common chronic pain condition characterized by widespread pain, is thought to originate largely from altered central neurotransmission. We compare a sample of 17 FM patients and 17 age- and sex matched healthy controls, using mu-opioid receptor (MOR) positron emission tomography. We demonstrate that FM patients display reduced MOR binding potential (BP) within several regions known to play a role in pain modulation, including the nucleus accumbens, the amygdala, and the dorsal cingulate. MOR BP in the accumbens of FM patients was negatively correlated with affective pain ratings. Moreover, MOR BP throughout the cingulate and the striatum was also negatively correlated with the relative amount of affective pain (McGill, affective score/sensory score) within these patients. These findings indicate altered endogenous opioid analgesic activity in FM and suggest a possible reason for why exogenous opiates appear to have reduced efficacy in this population. PMID- 17855615 TI - The itch-producing agents histamine and cowhage activate separate populations of primate spinothalamic tract neurons. AB - Itch is an everyday sensation, but when associated with disease or infection it can be chronic and debilitating. Several forms of itch can be blocked using antihistamines, but others cannot and these constitute an important clinical problem. Little information is available on the mechanisms underlying itch that is produced by nonhistaminergic mechanisms. We examined the responses of spinothalamic tract neurons to histaminergic and, for the first time, nonhistaminergic forms of itch stimuli. Fifty-seven primate spinothalamic tract (STT) neurons were identified using antidromic activation techniques and examined for their responses to histamine and cowhage, the nonhistaminergic itch-producing spicules covering the pod of the legume Mucuna pruriens. Each examined neuron had a receptive field on the hairy skin of the hindlimb and responded to noxious mechanical stimulation. STT neurons were tested with both pruritogens applied in a random order and we found 12 that responded to histamine and seven to cowhage. Each pruritogen-responsive STT neuron was activated by the chemical algogen capsaicin and two-thirds responded to noxious heat stimuli, demonstrating that these neurons convey chemical, thermal, and mechanical nociceptive information as well. Histamine or cowhage responsive STT neurons were found in both the marginal zone and the deep dorsal horn and were classified as high threshold and wide dynamic range. Unexpectedly, histamine and cowhage never activated the same cell. Our results demonstrate that the spinothalamic tract contains mutually exclusive populations of neurons responsive to histamine or the nonhistaminergic itch producing agent cowhage. PMID- 17855616 TI - Predicting odor pleasantness from odorant structure: pleasantness as a reflection of the physical world. AB - Although it is agreed that physicochemical features of molecules determine their perceived odor, the rules governing this relationship remain unknown. A significant obstacle to such understanding is the high dimensionality of features describing both percepts and molecules. We applied a statistical method to reduce dimensionality in both odor percepts and physicochemical descriptors for a large set of molecules. We found that the primary axis of perception was odor pleasantness, and critically, that the primary axis of physicochemical properties reflected the primary axis of olfactory perception. This allowed us to predict the pleasantness of novel molecules by their physicochemical properties alone. Olfactory perception is strongly shaped by experience and learning. However, our findings suggest that olfactory pleasantness is also partially innate, corresponding to a natural axis of maximal discriminability among biologically relevant molecules. PMID- 17855617 TI - Thalamic gating of auditory responses in telencephalic song control nuclei. AB - In songbirds, nucleus Uvaeformis (Uva) is the sole thalamic input to the telencephalic nucleus HVC (used as a proper name), a sensorimotor structure essential to learned song production that also exhibits state-dependent responses to auditory presentation of the bird's own song (BOS). The role of Uva in influencing HVC auditory activity is unknown. Using in vivo extracellular and intracellular recordings in urethane-anesthetized zebra finches, we characterized the auditory properties of Uva and examined its influence on auditory activity in HVC and in the telencephalic nucleus interface (NIf), the main auditory afferent of HVC and a corecipient of Uva input. We found robust auditory activity in Uva and determined that Uva is innervated by the ventral nucleus of lateral lemniscus, an auditory brainstem component. Thus, Uva provides a direct linkage between the auditory brainstem and HVC. Although low-frequency electrical stimulation in Uva elicited short-latency depolarizing postsynaptic potentials in HVC neurons, reversibly silencing Uva exerted little effect on BOS-evoked activity in HVC neurons. However, high-frequency stimulation in Uva suppressed auditory-evoked synaptic and suprathreshold activity in all HVC neuron types, a process accompanied by decreased input resistance of individual HVC neurons. Furthermore, high-frequency stimulation in Uva simultaneously suppressed auditory activity in HVC and NIf. These results suggest that Uva can gate auditory responses in HVC through a mechanism that involves inhibition local to HVC as well as withdrawal of auditory-evoked excitatory drive from NIf. Thus, Uva could play an important role in state-dependent gating of auditory activity in telencephalic sensorimotor structures important to learned vocal control. PMID- 17855618 TI - PIASx is a MEF2 SUMO E3 ligase that promotes postsynaptic dendritic morphogenesis. AB - Postsynaptic morphogenesis of dendrites is essential for the establishment of neural connectivity in the brain, but the mechanisms that govern postsynaptic dendritic differentiation remain poorly understood. Sumoylation of the transcription factor myocyte enhancer factor 2A (MEF2A) promotes the differentiation of postsynaptic granule neuron dendritic claws in the cerebellar cortex. Here, we identify the protein PIASx as a MEF2 SUMO E3 ligase that represses MEF2-dependent transcription in neurons. Gain-of-function and genetic knockdown experiments in rat cerebellar slices and in the postnatal cerebellum in vivo reveal that PIASx drives the differentiation of granule neuron dendritic claws in the cerebellar cortex. MEF2A knockdown suppresses PIASx-induced dendritic claw differentiation, and expression of sumoylated MEF2A reverses PIASx knockdown-induced loss of dendritic claws. These findings define the PIASx-MEF2 sumoylation signaling link as a key mechanism that orchestrates postsynaptic dendritic claw morphogenesis in the cerebellar cortex and suggest novel functions for SUMO E3 ligases in brain development and plasticity. PMID- 17855619 TI - Relationship between the phases of sensory and motor activity during a looming evoked multistage escape behavior. AB - The firing patterns of visual neurons tracking approaching objects need to be translated into appropriate motor activation sequences to generate escape behaviors. Locusts possess an identified neuron highly sensitive to approaching objects (looming stimuli), thought to play an important role in collision avoidance through its motor projections. To study how the activity of this neuron relates to escape behaviors, we monitored jumps evoked by looming stimuli in freely behaving animals. By comparing electrophysiological and high-speed video recordings, we found that the initial preparatory phase of jumps occurs on average during the rising phase of the firing rate of the looming-sensitive neuron. The coactivation period of leg flexors and extensors, which is used to store the energy required for the jump, coincides with the timing of the peak firing rate of the neuron. The final preparatory phase occurs after the peak and takeoff happens when the firing rate of the looming-sensitive neuron has decayed to <10% of its peak. Both the initial and the final preparatory phases and takeoff are triggered when the approaching object crosses successive threshold angular sizes on the animal's retina. Our results therefore suggest that distinct phases of the firing patterns of individual sensory neurons may actively contribute to distinct phases of complex, multistage motor behaviors. PMID- 17855620 TI - Selective loss of catecholaminergic wake active neurons in a murine sleep apnea model. AB - The presence of refractory wake impairments in many individuals with severe sleep apnea led us to hypothesize that the hypoxia/reoxygenation events in sleep apnea permanently damage wake-active neurons. We now confirm that long-term exposure to hypoxia/reoxygenation in adult mice results in irreversible wake impairments. Functionality and injury were next assessed in major wake-active neural groups. Hypoxia/reoxygenation exposure for 8 weeks resulted in vacuolization in the perikarya and dendrites and markedly impaired c-fos activation response to enforced wakefulness in both noradrenergic locus ceruleus and dopaminergic ventral periaqueductal gray wake neurons. In contrast, cholinergic, histaminergic, orexinergic, and serotonergic wake neurons appeared unperturbed. Six month exposure to hypoxia/reoxygenation resulted in a 40% loss of catecholaminergic wake neurons. Having previously identified NADPH oxidase as a major contributor to wake impairments in hypoxia/reoxygenation, the role of NADPH oxidase in catecholaminergic vulnerability was next addressed. NADPH oxidase catalytic and cytosolic subunits were evident in catecholaminergic wake neurons, where hypoxia/reoxygenation resulted in translocation of p67(phox) to mitochondria, endoplasmic reticulum, and membranes. Treatment with a NADPH oxidase inhibitor, apocynin, throughout hypoxia/reoxygenation exposures conferred protection of catecholaminergic neurons. Collectively, these data show that select wake neurons, specifically the two catecholaminergic groups, can be rendered persistently impaired after long-term exposure to hypoxia/reoxygenation, modeling sleep apnea; wake impairments are irreversible; catecholaminergic neurons are lost; and neuronal NADPH oxidase contributes to this injury. It is anticipated that severe obstructive sleep apnea in humans destroys catecholaminergic wake neurons. PMID- 17855621 TI - Nitric oxide mediates lymphatic vessel activation via soluble guanylate cyclase alpha1beta1-impact on inflammation. AB - The lymphatic vascular system regulates tissue fluid homeostasis and the afferent phase of the immune response, and it is also involved in tumor metastasis. There is increasing evidence that lymphatic vessels also mediate acute and chronic inflammation. However, the mechanisms and functional consequences of lymphangiogenesis under inflammatory conditions are largely unknown. Here, we show that lymphatic endothelial cells (LECs) specifically express the alpha1beta1 isoform of soluble guanylate cyclase (sGC), that vascular endothelial growth factor-A potently induces sGCalpha1beta1, and that nitric oxide (NO) -induced LEC proliferation, migration, and cGMP production in LECs are specifically dependent on sGCalpha1beta1. Moreover, the specific sGC inhibitor NS-2028 completely prevents ultraviolet B-irradiation-induced lymphatic vessel enlargement, edema formation, and skin inflammation in vivo. These findings identify a crucial role of the NO/sGCalpha1beta1/cGMP pathway in modulating lymphatic vessel function. The blockade of sGCalpha1beta1 signaling might serve as a novel therapeutic strategy for inhibiting lymphangiogenesis and inflammation, in addition to its effects on the blood vasculature. PMID- 17855622 TI - Peptide-mediated activation of Akt and extracellular regulated kinase signaling prevents lymphocyte apoptosis. AB - Lymphocyte apoptosis is a hallmark of sepsis and contributes to disease mortality. In other acute injuries, such as myocardial and cerebral ischemia/reperfusion, apoptosis plays a significant role in disease-associated morbidity and mortality. We previously showed that constitutive activation of the potent antiapoptotic Akt/protein kinase B signaling pathway in lymphocytes both reduces sepsis-induced lymphocyte apoptosis and confers a significant survival advantage compared to wild-type littermates. Here, we demonstrate a therapeutic approach to acutely augment Akt activity in a wild-type animal. A cell-permeable peptide conjugated to the Akt-binding domain of the endogenous Akt coactivator, Tcl-1, prolongs Akt activity, activates extracellular regulated kinase (ERK) signaling and protects lymphocytes from numerous apoptotic stimuli both in vitro and in vivo. Molecular approaches to activate the antiapoptotic Akt and ERK signaling pathways may provide a novel tool to study these signaling pathways, as well as a new antiapoptotic strategy for the treatment of sepsis and other acute injuries. PMID- 17855623 TI - Uncoupling protein-2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis-derived pyruvate utilization. AB - Uncoupling protein-2 (UCP2) belongs to the mitochondrial carrier family and has been thought to be involved in suppressing mitochondrial ROS production through uncoupling mitochondrial respiration from ATP synthesis. However, we show here that loss of function of UCP2 does not result in a significant increase in ROS production or an increased propensity for cells to undergo senescence in culture. Instead, Ucp2-/- cells display enhanced proliferation associated with a metabolic switch from fatty acid oxidation to glucose metabolism. This metabolic switch requires the unrestricted availability of glucose, and Ucp2-/- cells more readily activate autophagy than wild-type cells when deprived of glucose. Altogether, these results suggest that UCP2 promotes mitochondrial fatty acid oxidation while limiting mitochondrial catabolism of pyruvate. The persistence of fatty acid catabolism in Ucp2+/+ cells during a proliferative response correlates with reduced cell proliferation and enhances resistance to glucose starvation-induced autophagy. PMID- 17855624 TI - EGF regulates plasminogen activator inhibitor-1 (PAI-1) by a pathway involving c Src, PKCdelta, and sphingosine kinase 1 in glioblastoma cells. AB - Patients with gliomas expressing high levels of epidermal growth factor receptor (EGFR) and plasminogen activator inhibitor-1 (PAI-1) have a shorter overall survival prognosis. Moreover, EGF enhances PAI-1 expression in glioma cells. Although multiple known signaling cascades are activated by EGF in glioma cells, we show for the first time that EGF enhances expression of PAI-1 via sequential activation of c-Src, protein kinase C delta (PKCdelta), and sphingosine kinase 1 (SphK1), the enzyme that produces sphingosine-1-phosphate. EGF induced rapid phosphorylation of c-Src and PKCdelta and concomitant translocation of PKCdelta as well as SphK1 to the plasma membrane. Down-regulation of PKCdelta abolished EGF-induced SphK1 translocation and up-regulation of PAI-1 by EGF; whereas, down regulation of PKCalpha had no effect on the EGF-induced PAI-1 activation but enhanced its basal expression. Similarly, inhibition of c-Src activity by PP2 blocked both EGF-induced translocation of SphK1 and PKCdelta to the plasma membrane and up-regulation of PAI-1 expression. Furthermore, SphK1 was indispensable for both EGF-induced c-Jun phosphorylation and PAI-1 expression. Collectively, our results provide a functional link between three critical downstream targets of EGF, c-Src, PKCdelta, and SphK1 that have all been implicated in regulating motility and invasion of glioma cells. PMID- 17855625 TI - Gender differences in mRNA expression of ATP-binding cassette efflux and bile acid transporters in kidney, liver, and intestine of 5/6 nephrectomized rats. AB - ATP-binding cassette (ABC) transporters including multidrug resistance proteins (Mdr), multidrug resistance-associated proteins (Mrp), and breast cancer resistance protein (Bcrp/Abcg2) play major roles in tissue defense. Abcg5/g8 is essential in cholesterol efflux. The present study was aimed at elucidating alteration in expression of these transporters and bile-acid transporters during chronic kidney disease (CKD) and underlying molecular mechanisms. Seven weeks after 5/6 nephrectomy (Nx), mRNA expression of 16 aforementioned transporters in kidney, liver, jejunum, and large intestine of male and female Nx rats was quantified with the branched DNA signal amplification assay. In Nx males, intestinal expression of all the transporters remained unchanged; hepatic expression of most transporters was not altered, except increases in Mdr1a, Mrp3, and Abcg8. In male remnant kidneys, kidney-predominant transporter Abcg2 decreased and correlated with CKD severity, whereas Mdr1b, Mrp3, and ileal bile acid transporter increased and correlated with CKD severity. Such changes were largely absent in Nx females. Renal alterations of these transporters correlated with increases of cytokines and/or decreases of nuclear receptors such as estrogen receptor alpha and glucocorticoid receptor. Renal protein expression of Mrp2 increased, whereas that of Mrp4 remained unchanged in both genders of Nx rats. Treatment of rat proximal tubule NRK-52E cells with interleukin (IL)-1beta and IL-6 increased Mrp3 mRNA expression. In conclusion, during CKD, renal expression of many ABC transporters was altered at the transcriptional level, whereas hepatic mRNA expression of most ABC transporters remained unchanged. Down regulation of steroid hormone receptors and increase of inflammatory cytokines may contribute to alteration of transporter gene expression in kidney during CKD. PMID- 17855626 TI - Aberrant V(D)J recombination is not required for rapid development of H2ax/p53 deficient thymic lymphomas with clonal translocations. AB - Histone H2AX is required to maintain genomic stability in cells and to suppress malignant transformation of lymphocytes in mice. H2ax(-/-)p53(-/-) mice succumb predominantly to immature alphabeta T-cell lymphomas with translocations, deletions, and genomic amplifications that do not involve T-cell receptor (TCR). In addition, H2ax(-/-)p53(-/-) mice also develop at lower frequencies B and T lymphomas with antigen receptor locus translocations. V(D)J recombination is initiated through the programmed induction of DNA double-strand breaks (DSBs) by the RAG1/RAG2 endonuclease. Because promiscuous RAG1/RAG2 cutting outside of antigen receptor loci can promote genomic instability, H2ax(-/-)p53(-/-) T lineage lymphomas might arise, at least in part, through erroneous V(D)J recombination. Here, we show that H2ax(-/-)p53(-/-)Rag2(-/-) mice exhibit a similar genetic predisposition as do H2ax(-/-)p53(-/-) mice to thymic lymphoma with translocations, deletions, and amplifications. We also found that H2ax(-/ )p53(-/-)Rag2(-/-) mice often develop thymic lymphomas with loss or deletion of the p53(+) locus. Our data show that aberrant V(D)J recombination is not required for rapid onset of H2ax/p53-deficient thymic lymphomas with genomic instability and that H2ax deficiency predisposes p53(-/-)Rag2(-/-) thymocytes to transformation associated with p53 inactivation. Thus, H2AX is essential for suppressing the transformation of developing thymocytes arising from the aberrant repair of spontaneous DSBs. PMID- 17855627 TI - Simultaneous loss of beta- and gamma-catenin does not perturb hematopoiesis or lymphopoiesis. AB - Hematopietic stem cells (HSCs) maintain life-long hematopoiesis in the bone marrow via their ability to self-renew and to differentiate into all blood lineages. Although a central role for the canonical wnt signaling pathway has been suggested in HSC self-renewal as well as in the development of B and T cells, conditional deletion of beta-catenin (which is considered to be essential for Wnt signaling) has no effect on hematopoiesis or lymphopoiesis. Here, we address whether this discrepancy can be explained by a redundant and compensatory function of gamma-catenin, a close homolog of beta-catenin. Unexpectedly, we find that combined deficiency of beta- and gamma-catenin in hematopoietic progenitors does not impair their ability to self-renew and to reconstitute all myeloid, erythroid, and lymphoid lineages, even in competitive mixed chimeras and serial transplantations. These results exclude an essential role for canonical Wnt signaling (as mediated by beta- and/or gamma-catenin) during hematopoiesis and lymphopoiesis. PMID- 17855628 TI - I branching formation in erythroid differentiation is regulated by transcription factor C/EBPalpha. AB - The histo-blood group i and I antigens have been characterized as straight and branched repeats of N-acetyllactosamine, respectively, and the conversion of the straight-chain i to the branched-chain I structure on red cells is regulated to occur after birth. It has been demonstrated that the human I locus expresses 3 IGnT transcripts, IGnTA, IGnTB, and IGnTC, and that the last of these is responsible for the I branching formation on red cells. In the present investigation, the K-562 cell line was used as a model to show that the i-to-I transition in erythroid differentiation is determined by the transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha), which enhances transcription of the IGnTC gene, consequently leading to formation of the I antigen. Further investigation suggested that C/EBPalpha IGnTC-activation activity is modulated at a posttranslational level, and that the phosphorylation status of C/EBPalpha may have a crucial effect. Results from studies using adult and cord erythropoietic cells agreed with those derived using the K-562 cell model, with lentiviral expression of C/EBPalpha in CD34(+) hemopoietic cells demonstrating the determining role of C/EBPalpha in the induction of the IGnTC gene as well as in I antigen expression. PMID- 17855629 TI - PKC zeta mTOR pathway: a new target for rituximab therapy in follicular lymphoma. AB - Previous studies have documented that, in malignant B cells, rituximab elicits a complex and not yet totally understood signaling network contributing to its antitumor effect. In this context, we investigated the role of protein kinase C zeta (PKCzeta), an atypical PKC isoform, in the cellular response to rituximab. We found that follicular lymphoma cells displayed an increase in PKCzeta expression and activity levels, compared with nonmalignant B cells, and that this enzyme was a critical regulator of the classical MAPK module by stimulating Raf-1 kinase activity. PKCzeta appeared to be a significant contributor of abnormal mTOR regulation in follicular lymphoma cells through a MAPK-dependent mechanism. Rituximab was found to inhibit the PKCzeta/MAPK/mTOR module in these cells but not in other B-cell lymphomas. Importantly, the expression of a constitutively active form of PKCzeta resulted in an efficient protection of these cells toward rituximab. Altogether, our study describes a new regulatory component of mTOR pathway in follicular cell lymphoma and demonstrates that PKCzeta is a target for rituximab. Therefore, PKCzeta could represent an important parameter for rituximab efficacy and a promising target for future targeted therapy in follicular lymphoma. PMID- 17855630 TI - Immunoproteasome down-modulation enhances the ability of dendritic cells to stimulate antitumor immunity. AB - The process of dendritic cell (DC) maturation, critical for effective DC-based immunotherapy, also alters the proteasome such that peptides presented in the context of HLA class I are generated not by the constitutive proteasome, but by the immunoproteasome. Cytotoxic T lymphocytes (CTLs) induced by such DCs might not optimally recognize tumor cells normally expressing the constitutive proteasome. Using small interfering RNA (siRNA) transfection of DCs to inhibit expression of the 3 inducible immunoproteasome subunits in mature DCs, we found that such DCs expressed increased intracellular levels of constitutive proteasomes and presented an altered repertoire of tumor-antigenic peptides. When DCs generated from the monocytes of 3 patients with melanoma were transfected with immunoproteasome siRNA, induced to mature, and then trans-fected with RNA encoding defined melanoma antigens, these DCs were superior inducers of antigen specific CTLs against autologous melanoma cells. This alteration of DC proteasome composition, which enhances the ability of mature antigen-loaded DCs to stimulate anti-tumor immune responses, may lead to more effective DC-based tumor immunotherapy. PMID- 17855631 TI - Effect of single nucleotide polymorphisms on expression of the gene encoding thrombin-activatable fibrinolysis inhibitor: a functional analysis. AB - Thrombin-activable fibrinolysis inhibitor (TAFI) is a plasma zymogen that acts as a molecular link between coagulation and fibrinolysis. Numerous single nucleotide polymorphisms (SNPs) have been identified in CPB2, the gene encoding TAFI, and are located in the 5'-flanking region, in the coding sequences, and in the 3' untranslated region (UTR) of the CPB2 mRNA transcript. Associations between CPB2 SNPs and variation in plasma TAFI antigen concentrations have been described, but the identity of SNPs that are causally linked to this variation is not known. In the current study, we investigated the effect of the SNPs in the 5'-flanking region on CPB2 promoter activity and SNPs in the 3'-UTR on CPB2 mRNA stability. Whereas the 5'-flanking region SNPs (with 2 exceptions) did not have a significant effect on promoter activity, either alone or in haplotypic combinations seen in the human population, all of the 3'-UTR SNPs substantially affected mRNA stability. We speculate that these SNPs, in part, contribute to variation in plasma TAFI concentrations via modulation of CPB2 gene expression through an effect on mRNA stability. PMID- 17855632 TI - Hepatitis C virus infection and risk of posttransplantation lymphoproliferative disorder among solid organ transplant recipients. AB - Posttransplantation lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. Hepatitis C virus (HCV) infection has been linked to increased risk of lymphoma among immunocompetent individuals. We therefore investigated the association between HCV infection and PTLD in a retrospective cohort study of all individuals in the United States who received their first solid organ transplant from 1994 to 2005 (N = 210 763) using Scientific Registry of Transplant Recipients data. During follow-up, 1630 patients with PTLD were diagnosed. HCV prevalence at transplantation was 11.3%. HCV infection did not increase PTLD risk in the total cohort (Cox regression model, hazard ratio [HR] = 0.84; 95% confidence interval [CI] 0.68-1.05), even after adjustment for type of organ transplanted, indication for transplantation, degree of HLA mismatch, donor type, or use of immunosuppression medications. Additional analyses also revealed no association by PTLD subtype (defined by site, pathology, cell type, and tumor Epstein-Barr virus [EBV] status). HCV infection did increase PTLD risk among the 2.8% of patients (N = 5959) who were not reported to have received immunosuppression maintenance medications prior to hospital discharge (HR = 3.09; 95% CI, 1.14-8.42; P interaction = .007). Our findings suggest that HCV is not a major risk factor for PTLD, which is consistent with the model in which an intact immune system is necessary for development of HCV-related lymphoproliferation. PMID- 17855633 TI - A role for the MLL fusion partner ENL in transcriptional elongation and chromatin modification. AB - Chimeric proteins joining the histone methyltransferase MLL with various fusion partners trigger distinctive lymphoid and myeloid leukemias. Here, we immunopurified proteins associated with ENL, a protein commonly fused to MLL. Identification of these ENL-associated proteins (EAPs) by mass spectrometry revealed enzymes with a known role in transcriptional elongation (RNA polymerase II C-terminal domain kinase [RNAPolII CTD] positive transcription elongation factor b [pTEFb]), and in chromatin modification (histone-H3 methyltransferase DOT1L) as well as other frequent MLL partners (AF4, AF5q31, and LAF4), and polycomb group members (RING1, CBX8, and BCoR). The composition of EAP was further verified by coimmunoprecipitation, 2-hybrid analysis, pull-down, and colocalization experiments. Purified EAP showed a histone H3 lysine 79-specific methylase activity, displayed a robust RNAPolII CTD kinase function, and counteracted the effect of the pTEFb inhibitor 5,6-dichloro-benzimidazole riboside. In vivo, an ENL knock-down diminished genome-wide as well as gene specific H3K79 dimethylation, reduced global run-on elongation, and inhibited transient transcriptional reporter activity. According to structure-function data, DOT1L recruitment was important for transformation by the MLL-ENL fusion derivative. These results suggest a function of ENL in histone modification and transcriptional elongation. PMID- 17855634 TI - Overexpression of CDX2 perturbs HOX gene expression in murine progenitors depending on its N-terminal domain and is closely correlated with deregulated HOX gene expression in human acute myeloid leukemia. AB - The mechanisms underlying deregulation of HOX gene expression in AML are poorly understood. The ParaHox gene CDX2 was shown to act as positive upstream regulator of several HOX genes. In this study, constitutive expression of Cdx2 caused perturbation of leukemogenic Hox genes such as Hoxa10 and Hoxb8 in murine hematopoietic progenitors. Deletion of the N-terminal domain of Cdx2 abrogated its ability to perturb Hox gene expression and to cause acute myeloid leukemia (AML) in mice. In contrast inactivation of the putative Pbx interacting site of Cdx2 did not change the leukemogenic potential of the gene. In an analysis of 115 patients with AML, expression levels of CDX2 were closely correlated with deregulated HOX gene expression. Patients with normal karyotype showed a 14-fold higher expression of CDX2 and deregulated HOX gene expression compared with patients with chromosomal translocations such as t(8:21) or t(15;17). All patients with AML with normal karyotype tested were negative for CDX1 and CDX4 expression. These data link the leukemogenic potential of Cdx2 to its ability to dysregulate Hox genes. They furthermore correlate the level of CDX2 expression with HOX gene expression in human AML and support a potential role of CDX2 in the development of human AML with aberrant Hox gene expression. PMID- 17855635 TI - COQ2 nephropathy: a newly described inherited mitochondriopathy with primary renal involvement. AB - Primary coenzyme Q(10) (CoQ(10)) deficiency includes a group of rare autosomal recessive disorders primarily characterized by neurological and muscular symptoms. Rarely, glomerular involvement has been reported. The COQ2 gene encodes the para-hydroxybenzoate-polyprenyl-transferase enzyme of the CoQ(10) synthesis pathway. We identified two patients with early-onset glomerular lesions that harbored mutations in the COQ2 gene. The first patient presented with steroid resistant nephrotic syndrome at the age of 18 months as a result of collapsing glomerulopathy, with no extrarenal symptoms. The second patient presented at five days of life with oliguria, had severe extracapillary proliferation on renal biopsy, rapidly developed end-stage renal disease, and died at the age of 6 months after a course complicated by progressive epileptic encephalopathy. Ultrastructural examination of renal specimens from these cases, as well as from two previously reported patients, showed an increased number of dysmorphic mitochondria in glomerular cells. Biochemical analyses demonstrated decreased activities of respiratory chain complexes [II+III] and decreased CoQ(10) concentrations in skeletal muscle and renal cortex. In conclusion, we suggest that inherited COQ2 mutations cause a primary glomerular disease with renal lesions that vary in severity and are not necessarily associated with neurological signs. COQ2 nephropathy should be suspected when electron microscopy shows an increased number of abnormal mitochondria in podocytes and other glomerular cells. PMID- 17855636 TI - Parathyroid hormone regulates fibroblast growth factor-23 in a mouse model of primary hyperparathyroidism. AB - The importance of fibroblast growth factor 23 (FGF-23) in the pathogenesis of phosphate wasting disorders has been established, but controversy remains about how parathyroid hormone (PTH), which also stimulates urinary phosphate excretion, regulates the circulating level of FGF-23. We found that the serum FGF-23 concentration was higher in PTH-cyclin D1 transgenic mice, a model of primary hyperparathyroidism, than in wild-type mice. The serum FGF-23 concentration was significantly and directly correlated with serum PTH and calcium, and inversely correlated with phosphate levels in 90- to 118-week-old mice (all P < 0.005). Quantitative real-time reverse-transcriptase PCR revealed abundant expression of fgf23 in bone, especially in calvaria. The fgf23 expression in calvaria was significantly higher in the transgenic mice compared to the wild-type mice, and correlated well with serum FGF-23 levels. There was a direct correlation between the expression of fgf23 and the expression of osteocalcin and ALP, suggesting that activation of osteoblasts is important in the regulation of FGF-23. Serum FGF-23 levels decreased in the transgenic mice after parathyroidectomy. In conclusion, PTH plays a major role in the regulation of serum FGF-23 level in primary hyperparathyroidism, likely via activation of osteoblasts in bone. PMID- 17855637 TI - New insights into nephrogenic systemic fibrosis. AB - Nephrogenic systemic fibrosis is a new disorder reported almost exclusively in patients who have renal insufficiency and are exposed to contrast media formulated with gadolinium. High morbidity and mortality are associated with this severely disabling and painful condition. The acute phase begins upon exposure to gadolinium contrast media, characterized by a systemic inflammatory response involving iron mobilization, and then as a progressive, chronic phase in which fibrosis develops. Proposed is a unifying model of cumulative risk factors in which the interplay of systemic inflammation and stimulated hematopoietic environment associated with hyperparathyroidism and erythropoietin may tie to a common pathogenic mechanism of fibrogenesis. Because there are no uniformly effective interventions to treat nephrogenic systemic fibrosis other than successful renal transplantation, prevention by avoiding gadolinium contrast media in patients with chronic kidney disease is vital. On the basis of suspected pathogenesis, it is also reasonable to limit erythropoietin and iron therapy to dosages ensuring recommended targets and adequately control hyperparathyroidism. Herein is reviewed what is currently known about this subject. PMID- 17855638 TI - Age affects outcomes in chronic kidney disease. AB - Chronic kidney disease (CKD) is common among the elderly. However, little is known about how the clinical implications of CKD vary with age. We examined the age-specific incidence of death, treated end-stage renal disease (ESRD), and change in estimated glomerular filtration rate (eGFR) among 209,622 US veterans with CKD stages 3 to 5 followed for a mean of 3.2 years. Patients aged 75 years or older at baseline comprised 47% of the overall cohort and accounted for 28% of the 9227 cases of ESRD that occurred during follow-up. Among patients of all ages, rates of both death and ESRD were inversely related to eGFR at baseline. However, among those with comparable levels of eGFR, older patients had higher rates of death and lower rates of ESRD than younger patients. Consequently, the level of eGFR below which the risk of ESRD exceeded the risk of death varied by age, ranging from 45 ml/min per 1.73 m(2) for 18 to 44 year old patients to 15 ml/min per 1.73 m(2) for 65 to 84 year old patients. Among those 85 years or older, the risk of death always exceeded the risk of ESRD in this cohort. Among patients with eGFR levels <45 ml/min per 1.73 m(2) at baseline, older patients were less likely than their younger counterparts to experience an annual decline in eGFR of >3 ml/min per 1.73 m(2). In conclusion, age is a major effect modifier among patients with an eGFR of <60 ml/min per 1.73 m(2), challenging us to move beyond a uniform stage-based approach to managing CKD. PMID- 17855639 TI - Thiazide diuretics exacerbate fructose-induced metabolic syndrome. AB - Fructose is a commonly used sweetener associated with diets that increase the prevalence of metabolic syndrome. Thiazide diuretics are frequently used in these patients for treatment of hypertension, but they also exacerbate metabolic syndrome. Rats on high-fructose diets that are given thiazides exhibit potassium depletion and hyperuricemia. Potassium supplementation improves their insulin resistance and hypertension, whereas allopurinol reduces serum levels of uric acid and ameliorates hypertension, hypertriglyceridemia, hyperglycemia, and insulin resistance. Both potassium supplementation and treatment with allopurinol also increase urinary nitric oxide excretion. We suggest that potassium depletion and hyperuricemia in rats exacerbates endothelial dysfunction and lowers the bioavailability of nitric oxide, which blocks insulin activity and causes insulin resistance during thiazide usage. Addition of potassium supplements and allopurinol with thiazides might be helpful in the management of metabolic syndrome. PMID- 17855640 TI - Evidence of oligogenic inheritance in nephronophthisis. AB - Nephronophthisis is a recessive cystic renal disease that leads to end-stage renal failure in the first two decades of life. Twenty-five percent of nephronophthisis cases are caused by large homozygous deletions of NPHP1, but six genes responsible for nephronophthisis have been identified. Because oligogenic inheritance has been described for the related Bardet-Biedl syndrome, we evaluated whether mutations in more than one gene may also be detected in cases of nephronophthisis. Because the nephrocystins 1 to 4 are known to interact, we examined patients with nephronophthisis from 94 different families and sequenced all exons of the NPHP1, NPHP2, NPHP3, and NPHP4 genes. In our previous studies involving 44 families, we detected two mutations in one of the NPHP1-4 genes. Here, we detected in six families two mutations in either NPHP1, NPHP3, or NPHP4, and identified a third mutation in one of the other NPHP genes. Furthermore, we found possible digenic disease by detecting one individual who carried one mutation in NPHP2 and a second mutation in NPHP3. Finally, we detected the presence of a single mutation in nine families, suggesting that the second recessive mutation may be in another as yet unidentified NPHP gene. Our findings suggest that oligogenicity may occur in cases of nephronophthisis. PMID- 17855641 TI - Evaluation of the modification of diet in renal disease study equation in a large diverse population. AB - Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease. Performance of the Modification of Diet in Renal Disease (MDRD) Study equation varies substantially among populations. To describe the performance of the equation in a large, diverse population, estimated GFR (eGFR) was compared to measured GFR (mGFR) in a cross-sectional analysis of 5504 participants in 10 studies that included measurements of standardized serum creatinine and urinary clearance of iothalamate. At eGFR <60 ml/min per 1.73 m(2), the MDRD Study equation had lower bias and higher precision than at eGFR > or =60 ml/min per 1.73 m(2). The accuracy of the equation, measured by the percent of estimates that fell within 30% of mGFR, was similar for eGFR values above or below 60 ml/min per 1.73 m(2) (82% and 84%, respectively). Differences in performance among subgroups defined by age, sex, race, diabetes, transplant status, and body mass index were small when eGFR was <60 ml/min per 1.73 m(2). The MDRD Study equation therefore provides unbiased and reasonably accurate estimates across a wide range of subgroups when eGFR is <60 ml/min per 1.73 m(2). In individual patients, interpretation of GFR estimates near 60 ml/min per 1.73 m(2) should be interpreted with caution to avoid misclassification of chronic kidney disease in the context of the clinical setting. PMID- 17855642 TI - Smad7 transgene attenuates peritoneal fibrosis in uremic rats treated with peritoneal dialysis. AB - Transforming growth factor beta (TGF-beta) plays a critical role in the pathogenesis of the peritoneal fibrosis that complicates long-term peritoneal dialysis (PD). We studied the TGF-beta/Smad signaling pathway in peritoneal fibrosis induced in uremic rats treated with PD and explored the therapeutic potential of Smad7 to prevent fibrogenesis. After subtotal nephrectomy, uremic rats were treated with peritoneal dialysis using 4.25% dextrose-containing fluid. The peritoneum of uremic rats treated with PD demonstrated fibrosis, increased TGF-beta expression, increased Smad2/3 activation, decreased Smad7 expression, and increased expression of fibrogenic and angiogenic factors. In addition, peritoneal function was impaired and its structure was altered, including a thickened submesothelial layer. In rats transfected with a Smad7 transgene using an ultrasound-microbubble-mediated system, peritoneal fibrosis was attenuated, peritoneal function was improved, and Smad2/3 activation was inhibited. We suggest that administration of Smad7 inhibits peritoneal fibrogenesis in uremic rats treated with PD by correcting the imbalance between downregulated Smad7 and activated Smad2/3. Blockade of the TGF-beta/Smad signaling pathway may represent a novel therapeutic approach to prevent peritoneal fibrosis in patients treated with PD. PMID- 17855643 TI - Role of altered renal lipid metabolism in the development of renal injury induced by a high-fat diet. AB - Metabolic syndrome is associated with increased risk of chronic kidney disease, and the renal injury in patients with metabolic syndrome may be a result of altered renal lipid metabolism. We fed wild-type or insulin-sensitive heterozygous peroxisome proliferator-activated receptor gamma-deficient (PPARgamma(+/-)) mice a high-fat diet for 16 weeks. In wild-type mice, this diet induced core features of metabolic syndrome, subsequent renal lipid accumulation, and renal injury including glomerulosclerosis, interstitial fibrosis, and albuminuria. Renal lipogenesis accelerated, determined by increased renal mRNA expression of the lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase (ACC) and by increased ACC activity. In addition, renal lipolysis was suppressed, determined by reduced mRNA expression of the lipolytic enzyme carnitine palmitoyl acyl-CoA transferase 1 and by reduced activity of AMP activated protein kinase. In PPARgamma(+/-) mice, renal injury, systemic metabolic abnormalities, renal accumulation of lipids, and the changes in renal lipid metabolism were attenuated. Thus, a high-fat diet leads to an altered balance between renal lipogenesis and lipolysis, subsequent renal accumulation of lipid, and renal injury. We suggest that renal lipid metabolism could serve as a new therapeutic target to prevent chronic kidney disease in patients with metabolic syndrome. PMID- 17855644 TI - Reduced expression of insulin receptors in the kidneys of insulin-resistant rats. AB - Insulin resistance is accompanied by hyperinsulinemia and activation of the renin angiotensin system, both of which are associated with hypertension. Because the kidney plays a major role in the regulation of blood pressure, we studied the regulation of insulin receptor expression in the kidney during states of insulin resistance. Using two rat models of insulin resistance, Western blot analysis demonstrated a significant reduction in the expression of insulin receptor subunits in the kidney compared to lean control rats. Treatment of insulin resistance in Zucker rats with the insulin-sensitizing drug rosiglitazone partially restored renal insulin receptor levels. Conversely, treatment with the angiotensin II type 1 receptor (AT1) antagonist candesartan increased renal insulin receptor expression compared to untreated rats. Streptozotocin-induced hyperglycemia, which results from hypoinsulinemia, reduced expression of renal insulin receptors. Hyperinsulinemia induced by insulin infusion, however, did not produce a similar effect. In conclusion, insulin receptors are downregulated in the kidneys of insulin resistant rats, possibly mediated by hyperglycemia and angiotensin II. PMID- 17855645 TI - A humanized mouse model of idiopathic nephrotic syndrome suggests a pathogenic role for immature cells. AB - Idiopathic nephrotic syndrome is characterized by glomerular proteinuria in the absence of infiltrating cells or immunoglobulin deposits. Although it is suspected that T cells secrete a circulating factor that leads to proteinuria by altering the permeability of the glomerular filtration barrier, the precise etiology of this syndrome is unknown. Because an animal model that mimics human idiopathic nephrotic syndrome does not exist, we developed a humanized mouse model of the disease by injecting CD34(+) stem cells or CD34(-) peripheral blood mononuclear cells from afflicted patients into immunocompromised mice. Even though both CD34(+) and CD34(-) cells induced the engraftment of human CD45(+) leukocytes in mice, only the injection of CD34(+) stem cells induced albuminuria. Ultrastructural analysis of glomeruli from the resulting proteinuric mice revealed effacement of podocyte foot processes, similar to the pathology observed in the human disease. Therefore, our data suggest that the cells responsible for the pathogenesis of idiopathic nephrotic syndrome are more likely to be immature differentiating cells rather than mature peripheral T cells. PMID- 17855646 TI - Origin and fate of pendrin-positive intercalated cells in developing mouse kidney. AB - Pendrin is an apical anion exchanger found in type B and nonA-nonB intercalated cells that is involved in bicarbonate secretion. The purpose of this study was to establish the origin and fate of pendrin-positive intercalated cells in the mouse kidney. Using immunohistochemistry, we found that pendrin-positive cells first appeared in the connecting tubule at embryonic day 14 (E14) and subsequently in the medullary collecting duct at E18. Most of the pendrin-positive cells in the connecting tubule were nonA-nonB intercalated cells, wheras those in the medullary collecting duct were type B intercalated cells. In the cortical collecting duct, pendrin-positive cells appeared in the inner part at day 4 after birth and in the outer part at day 7. Pendrin-positive cells gradually disappeared by apoptosis from the inner part of the medullary collecting duct two weeks after birth. Using 5-bromo-2'deoxy-uridine (BrdU) to follow cell proliferation, we determined that selective proliferation of pendrin-positive intercalated cells does not occur; instead, these cells may arise from undifferentiated precursor cells from separate foci, one in the connecting tubule and one in the collecting duct. PMID- 17855647 TI - Race and mortality after acute renal failure. AB - Black patients receiving dialysis for end-stage renal disease in the United States have lower mortality rates than white patients. Whether racial differences exist in mortality after acute renal failure is not known. We studied acute renal failure in patients hospitalized between 2000 and 2003 using the Nationwide Inpatient Sample and found that black patients had an 18% (95% confidence interval [CI] 16 to 21%) lower odds of death than white patients after adjusting for age, sex, comorbidity, and the need for mechanical ventilation. Similarly, among those with acute renal failure requiring dialysis, black patients had a 16% (95% CI 10 to 22%) lower odds of death than white patients. In stratified analyses of patients with acute renal failure, black patients had significantly lower adjusted odds of death than white patients in settings of coronary artery bypass grafting, cardiac catheterization, acute myocardial infarction, congestive heart failure, pneumonia, sepsis, and gastrointestinal hemorrhage. Black patients were more likely than white patients to be treated in hospitals that care for a larger number of patients with acute renal failure, and black patients had lower in-hospital mortality than white patients in all four quartiles of hospital volume. In conclusion, in-hospital mortality is lower for black patients with acute renal failure than white patients. Future studies should assess the reasons for this difference. PMID- 17855648 TI - Platelets take up the monoclonal antibody bevacizumab. AB - PURPOSE: One of the key factors that promotes angiogenesis is vascular endothelial growth factor (VEGF). Platelets are the main source of VEGF in blood and contribute to angiogenesis by release of growth factors, including VEGF, from their alpha-granules on activation. The monoclonal antibody bevacizumab blocks VEGF in the blood of patients within hours after administration. Platelets are known to endocytose plasma proteins including immunoglobulins. We tested the hypothesis that platelets take up bevacizumab. EXPERIMENTAL DESIGN: Fluorescence activated cell sorting analysis, immunofluorescence imaging, and Western blotting were used to study uptake and release of bevacizumab by platelets in vitro and in vivo. The angiogenic activity of platelets preincubated with bevacizumab was studied in endothelial proliferation assays. Finally, we determined whether treatment with bevacizumab neutralizes VEGF in platelets from cancer patients. RESULTS: We found that platelets are able to take up bevacizumab. Activation of platelets preincubated with bevacizumab resulted in release of the antibody and release of VEGF neutralized by bevacizumab. Immunofluorescence microscopy revealed that FITC-labeled bevacizumab and P-selectin colocalize, indicating alpha-granule localization. In addition, bevacizumab uptake inhibited platelet induced human endothelial cell proliferation. In in vivo rabbit experiments, FITC labeled bevacizumab was present in platelets after 2 h and up to 2 weeks following i.v. administration. Finally, we found that platelets take up bevacizumab in patients receiving bevacizumab treatment. Within 8 h after bevacizumab administration, platelet VEGF was almost completely neutralized due to this uptake. CONCLUSION: These studies show that bevacizumab is taken up by platelets and may explain its clinical effect on wound healing and tumor growth. PMID- 17855649 TI - Genetically targeted T cells eradicate systemic acute lymphoblastic leukemia xenografts. AB - PURPOSE: Human T cells targeted to the B cell-specific CD19 antigen through retroviral-mediated transfer of a chimeric antigen receptor (CAR), termed 19z1, have shown significant but partial in vivo antitumor efficacy in a severe combined immunodeficient (SCID)-Beige systemic human acute lymphoblastic leukemia (NALM-6) tumor model. Here, we investigate the etiologies of treatment failure in this model and design approaches to enhance the efficacy of this adoptive strategy. EXPERIMENTAL DESIGN: A panel of modified CD19-targeted CARs designed to deliver combined activating and costimulatory signals to the T cell was generated and tested in vitro to identify an optimal second-generation CAR. Antitumor efficacy of T cells expressing this optimal costimulatory CAR, 19-28z, was analyzed in mice bearing systemic costimulatory ligand-deficient NALM-6 tumors. RESULTS: Expression of the 19-28z CAR, containing the signaling domain of the CD28 receptor, enhanced systemic T-cell antitumor activity when compared with 19z1 in treated mice. A treatment schedule of 4 weekly T-cell injections, designed to prolong in vivo T-cell function, further improved long-term survival. Bioluminescent imaging of tumor in treated mice failed to identify a conserved site of tumor relapse, consistent with successful homing by tumor-specific T cells to systemic sites of tumor involvement. CONCLUSIONS: Both in vivo costimulation and repeated administration enhance eradication of systemic tumor by genetically targeted T cells. The finding that modifications in CAR design as well as T-cell dosing allowed for the complete eradication of systemic disease affects the design of clinical trials using this treatment strategy. PMID- 17855650 TI - Serpin peptidase inhibitor clade A member 1 as a potential marker for malignancy in insulinomas. AB - PURPOSE: The biological behavior of insulinomas cannot be predicted based on histopathologic criteria in which the diagnosis of malignancy is confirmed by the presence of metastases. In this study, microarray and quantitative real-time reverse transcription-PCR were applied to identify differentially expressed genes between malignant and nonmalignant insulinomas to search for useful biomarkers to recognize the metastatic potential of insulinomas. EXPERIMENTAL DESIGN: Code Link human bioarrays were used to analyze differences in approximately 20,000 genes between six well-differentiated endocrine tumors of benign behavior compared with one well-differentiated endocrine carcinoma (WDEC) and three metastases of endocrine carcinomas (MEC). Quantitative real-time reverse transcription-PCR was used to validate differential expressions of five genes in a series of 35 sporadic insulinomas. Serpin peptidase inhibitor clade A member 1 (SERPINA1; alpha-1-antitrypsin) expression, identified as up-regulated in malignant insulinomas, was also evaluated by immunohistochemistry. RESULTS: Analysis of microarray data resulted in 230 differentially expressed genes. Gene Ontology analysis identified serine-type endopeptidase activity and serine-type endopeptidase inhibitor activity as pathways presenting significant differential expression. Protease serine 2 and complement factor B (from serine-type endopeptidase activity pathway) were respectively confirmed as up-regulated in well-differentiated endocrine tumors of benign behavior (WDET) and in WDEC/MEC. Angiotensinogen and SERPINA1 (from serine-type endopeptidase inhibitor activity pathway) were confirmed as up-regulated in WDEC/MEC. SERPINA1 was shown to be expressed in 85.7% of malignant versus 14.3% of nonmalignant insulinomas by immunohistochemistry. CONCLUSIONS: Our data are consistent to the possibility that SERPINA1 is a marker of malignancy in insulinomas. Given the widespread availability of antibody anti-alpha-1-antitrypsin in pathology services, SERPINA1 expression evaluation might be of clinical utility in recognizing patients more likely to develop an aggressive presentation. PMID- 17855651 TI - Regulation of tissue-specific expression of the human and mouse urate transporter 1 gene by hepatocyte nuclear factor 1 alpha/beta and DNA methylation. AB - Expression of Urate transporter 1 (URAT1/SLC22A12) is restricted to the proximal tubules in the kidney, where it is responsible for the tubular reabsorption of urate. To elucidate the mechanism underlying its tissue-specific expression, the transcriptional regulation of the hURAT1 and mUrat1 genes was investigated. Hepatocyte nuclear factor 1 alpha (HNF1alpha) and HNF1beta positively regulate minimal promoter activity of the URAT1 gene as shown by reporter gene assays. Electrophoretic mobility shift assays revealed binding of HNF1alpha and/or HNF1beta to the HNF1 motif in the hURAT1 promoter. Furthermore, the mRNA expression of Urat1 is reduced in the kidneys of Hnf1alpha-null mice compared with wild-type mice, confirming the indispensable role of HNF1alpha in the constitutive expression of URAT1 genes. It was also shown that the proximal promoter region of mUrat1 was hypermethylated in the liver and kidney medulla, whereas this region was relatively hypomethylated in the kidney cortex. These methylation profiles are in a good agreement with the proximal tubule-restricted expression of mUrat1 in the kidney cortex. Taken together, these results strongly suggest that tissue-specific expression of the URAT1 genes is coordinately regulated by the transcriptional activation by HNF1alpha/HNF1beta heterodimer and repression by DNA methylation. PMID- 17855652 TI - K252a prevents nigral dopaminergic cell death induced by 6-hydroxydopamine through inhibition of both mixed-lineage kinase 3/c-Jun NH2-terminal kinase 3 (JNK3) and apoptosis-inducing kinase 1/JNK3 signaling pathways. AB - It is well documented that the mitogen-activated protein kinase pathway plays a pivotal role in rats with 6-hydroxydopamine (6-OHDA)-induced unilateral lesion in the nigrostriatal system. Our recent studies have shown that mixed-lineage kinase 3 (MLK3) and apoptosis-inducing kinase 1 (ASK1) are all involved in neuronal cell death induced by ischemia, which is mediated by the MLK3/c-Jun NH2-terminal kinase 3 (JNK3) and ASK1/JNK signaling pathway. To investigate whether these pathways are correlated with 6-OHDA-induced lesion as well, we examined the phosphorylation of MLK3, ASK1, and JNK3 in 6-OHDA rats. The results showed that both MLK3 and ASK1 could activate JNK3 and then subsequently enhance the neuronal death through its downstream pathways (i.e., nuclear and non-nuclear pathway). K252a have wide-range effects including Trk inhibition, MLK3 inhibition, and activation of phosphatidylinositol 3 kinase and mitogen-activated protein kinase kinase signaling pathways through interactions with distinct targets and is a well known neuroprotective compound. We found that K252a could protect dopaminergic neurons against cell program death induced by 6-OHDA lesion, and the phenotypes of 6-OHDA rat model treated with K252a were partial rescued. The inhibition of K252a on the activation of MLK3/JNK3 and ASK1/JNK3 provided a link between 6-OHDA lesion and stress-activated kinases. It suggested that both proapoptotic MLK3/JNK3 and ASK1/JNK3 cascade may play an important role in dopaminergic neuronal death in 6-OHDA insult. Thus, the JNK3 signaling may eventually emerge as a prime target for novel therapeutic approaches to treatment of Parkinson disease, and K252a may serve as a potential and important neuroprotectant in therapeutic aspect in Parkinson disease. PMID- 17855653 TI - Decursin suppresses human androgen-independent PC3 prostate cancer cell proliferation by promoting the degradation of beta-catenin. AB - Alterations in the Wnt/beta-catenin pathway are associated with the development and progression of human prostate cancer. Decursin, a pyranocoumarin isolated from the Korean Angelica gigas root, inhibits the growth of androgen-independent human prostate cancer cells, but little is known about its mechanism of action. Using a cell-based screen, we found that decursin attenuates the Wnt/beta-catenin pathway. Decursin antagonized beta-catenin response transcription (CRT), which was induced with Wnt3a-conditioned medium and LiCl, by promoting the degradation of beta-catenin. Furthermore, decursin suppressed the expression of cyclin D1 and c-myc, which are downstream target genes of beta-catenin and thus inhibited the growth of PC3 prostate cancer cells. In contrast, decursinol, in which the (CH3)2 C=CH-COO- side chain of decursin is replaced with -OH, had no effect on CRT, the level of intracellular beta-catenin, or PC3 cell proliferation. Our findings suggest that decursin exerts its anticancer activity in prostate cancer cells via inhibition of the Wnt/beta-catenin pathway. PMID- 17855654 TI - Identification of a postendocytic sorting sequence in CCR5. AB - The chemokine receptor 5 (CCR5), a member of the G protein-coupled receptor family (GPCR), is used by human immunodeficiency virus type 1 (HIV-1) with a R5 tropism as an entry receptor in addition to CD4. It is a key target for an antiviral action aiming at inhibiting the HIV-1 entry process. Only few data are available today regarding the mechanism involved in the intracellular trafficking process of CCR5. Understanding how CCR5 cell surface expression is regulated is particularly important with regard to HIV-1 entry inhibition. We set out to investigate whether CCR5 molecular determinants were involved in the postendocytic recycling and degradative pathways. We constructed progressive deletion mutants of the C-terminal domain of CCR5 that we stably expressed in HEK293 cells. All of the deletion mutants were expressed at the cell surface and were functional HIV-1 receptors. The deletion mutants were internalized after stimulation, but they lost their ability to recycle to the plasma membrane. They were rerouted toward a lysosomal degradative pathway. We identified here a sequence of four amino acids, present at the extreme C terminus of CCR5, that is necessary for the recycling of the internalized receptor, independently of its phosphorylation. A detailed analysis of this sequence indicated that the four amino acids acted as a postsynaptic density 95/discs-large/zona occludens (PDZ) interacting sequence. These results show that the CCR5 cytoplasmic domain bears a sequence similar to the "recycling signals" previously identified in other GPCRs. Drugs able to disrupt the recycling pathway of CCR5 may constitute promising tools for therapeutic treatment. PMID- 17855655 TI - Mitochondrial expression of the Drosophila melanogaster multisubstrate deoxyribonucleoside kinase. AB - The multisubstrate deoxyribonucleoside kinase from Drosophila melanogaster deoxyribonucleoside kinase (Dm-dNK) is studied as a candidate suicide gene for applications in combined gene/chemotherapy of cancer. We have created an engineered Dm-dNK nucleoside kinase that is targeted to the mitochondrial matrix. The enzyme was expressed in a thymidine kinase 1-deficient osteosarcoma cell line, and the sensitivity of the cells to cytotoxic nucleoside analogs was determined when the enzyme was targeted to either the nucleus or the mitochondrial matrix. Although the total deoxythymidine (dThd) phosphorylation activity was similar in cells expressing Dm-dNK in the nucleus or in the mitochondria, the cells expressing the enzyme in the mitochondria showed higher sensitivity to the antiproliferative activity of several pyrimidine nucleoside analogs, such as (E)-5-(2-bromovinyl)-2'-deoxyuridine, 5-bromo-2'-deoxyuridine, and 5-fluoro-2'-deoxyuridine. Labeling studies using [3H]dThd showed that the cells expressing the mitochondrial enzyme had an increased incorporation of [3H]dThd into DNA, shown to be due to a higher [3H]dTTP specific activity of the total dTTP pool in the cells in which Dm-dNK was targeted to the mitochondria. The difference in the specific activity of the dTTP pool is a result of different contributions of the de novo and the salvage pathways for the dTTP synthesis in transduced cells. In summary, these findings suggest that mitochondrial targeting of Dm-dNK facilitates nucleoside and nucleoside analog phosphorylation and could be used as a strategy to enhance the efficacy of nucleoside analog phosphorylation and concomitantly their cytostatic potential. PMID- 17855656 TI - Response to the FDA's May 23, 2007, nephrogenic systemic fibrosis update. PMID- 17855657 TI - Breast cancer molecular signatures as determined by SAGE: correlation with lymph node status. AB - Global gene expression measured by DNA microarray platforms have been extensively used to classify breast carcinomas correlating with clinical characteristics, including outcome. We generated a breast cancer Serial Analysis of Gene Expression (SAGE) high-resolution database of approximately 2.7 million tags to perform unsupervised statistical analyses to obtain the molecular classification of breast-invasive ductal carcinomas in correlation with clinicopathologic features. Unsupervised statistical analysis by means of a random forest approach identified two main clusters of breast carcinomas, which differed in their lymph node status (P=0.01); this suggested that lymph node status leads to globally distinct expression profiles. A total of 245 (55 up-modulated and 190 down modulated) transcripts were differentially expressed between lymph node (+) and lymph node (-) primary breast tumors (fold change, >or=2; P<0.05). Various lymph node (+) up-modulated transcripts were validated in independent sets of human breast tumors by means of real-time reverse transcription-PCR (RT-PCR). We validated significant overexpression of transcripts for HOXC10 (P=0.001), TPD52L1 (P=0.007), ZFP36L1 (P=0.011), PLINP1 (P=0.013), DCTN3 (P=0.025), DEK (P=0.031), and CSNK1D (P=0.04) in lymph node (+) breast carcinomas. Moreover, the DCTN3 (P=0.022) and RHBDD2 (P=0.002) transcripts were confirmed to be overexpressed in tumors that recurred within 6 years of follow-up by real-time RT-PCR. In addition, meta-analysis was used to compare SAGE data associated with lymph node (+) status with publicly available breast cancer DNA microarray data sets. We have generated evidence indicating that the pattern of gene expression in primary breast cancers at the time of surgical removal could discriminate those tumors with lymph node metastatic involvement using SAGE to identify specific transcripts that behave as predictors of recurrence as well. PMID- 17855658 TI - Sox10 has a broad expression pattern in gliomas and enhances platelet-derived growth factor-B--induced gliomagenesis. AB - In a previously published insertional mutagenesis screen for candidate brain tumor genes in the mouse using a Moloney mouse leukemia virus encoding platelet derived growth factor (PDGF)-B, the Sox10 gene was tagged in five independent tumors. The proviral integrations suggest an enhancer effect on Sox10. All Moloney murine leukemia virus/PDGFB tumors had a high protein expression of Sox10 independently of malignant grade or tumor type. To investigate the role of Sox10 in gliomagenesis, we used the RCAS/tv-a mouse model in which the expression of retroviral-encoded genes can be directed to glial progenitor cells (Ntv-a mice). Both Ntv-a transgenic mice, wild-type, and Ntv-a p19Arf null mice were injected with RCAS-SOX10 alone or in combination with RCAS-PDGFB. Infection with RCAS SOX10 alone did not induce any gliomas. Combined infection of RCAS-SOX10 and RCAS PDGFB in wild-type Ntv-a mice yielded a tumor frequency of 12%, and in Ntv-a Arf /- mice the tumor frequency was 30%. This indicates that Sox10 alone is not sufficient to induce gliomagenesis but acts synergistically with PDGFB in glioma development. All induced tumors displayed characteristics of PNET-like structures and oligodendroglioma. The tumors had a strong and widely distributed expression of Sox10 and PDGFR-alpha. We investigated the expression of Sox10 in other human tumors and in a number of gliomas. The Sox10 expression was restricted to gliomas and melanomas. All glioma types expressed Sox10, and tumors of low-grade glioma had a much broader distribution of Sox10 compared with high-grade gliomas. PMID- 17855659 TI - Increased expression and activity of nuclear cathepsin L in cancer cells suggests a novel mechanism of cell transformation. AB - It is generally accepted that the role of cathepsin L in cancer involves its activities outside the cells once it has been secreted. However, cathepsin L isoforms that are devoid of a signal peptide were recently shown to be present in the nucleus where they proteolytically process the CCAAT-displacement protein/cut homeobox (CDP/Cux) transcription factor. A role for nuclear cathepsin L in cell proliferation could be inferred from the observation that the CDP/Cux processed isoform can accelerate entry into S phase. Here, we report that in many transformed cells the proteolytic processing of CDP/Cux is augmented and correlates with increased cysteine protease expression and activity in the nucleus. Taking advantage of an antibody that recognizes the prodomain of human cathepsin L, we showed that human cells express short cathepsin L species that do not contain a signal peptide, do not transit through the endoplasmic reticulum, are not glycosylated, and localize to the nucleus. We also showed that transformation by the ras oncogene causes rapid increases both in the production of short nuclear cathepsin L isoforms and in the processing of CDP/Cux. Using a cell-based assay, we showed that a cell-permeable inhibitor of cysteine proteases is able to delay the progression into S phase and the proliferation in soft agar of ras-transformed cells, whereas the non-cell-permeable inhibitor had no effect. Taken together, these results suggest that the role of cathepsin L in cancer might not be limited to its extracellular activities but may also involve its processing function in the nucleus. PMID- 17855660 TI - Pim-1 kinase-dependent phosphorylation of p21Cip1/WAF1 regulates its stability and cellular localization in H1299 cells. AB - Previous studies from our laboratory showed that p21Cip1/WAF1 can be phosphorylated by Pim-1 kinase in vitro, implying that part of the function of Pim-1 might involve influencing the cell cycle. In the present study, site directed mutagenesis and phosphorylated-specific antibodies were used as tools to identify the sites phosphorylated by Pim-1 and the consequences of this phosphorylation. What we found was that Pim-1 can efficiently phosphorylate p21 on Thr145 in vitro using recombinant protein and in vivo in intact cells. Unexpectedly, we found that Ser146 is a second site that is phosphorylated in vivo, but this phosphorylation event seems to be an indirect result of Pim-1 expression. More importantly, the consequences of phosphorylation of either Thr145 or Ser146 are distinct. When p21 is phosphorylated on Thr145, it localizes to the nucleus and results in the disruption of the association between proliferating cell nuclear antigen and p21. Furthermore, phosphorylation of Thr145 promotes stabilization of p21. On the other hand, when p21 is phosphorylated on Ser146, it localizes primarily in the cytoplasm and the effect of phosphorylation on stability is minimal. Cotransfection of wild-type Pim-1 with p21 increases the rate of proliferation compared with cotransfection of p21 with kinase-dead Pim-1. Knocking down Pim-1 expression greatly decreases the rate of proliferation of H1299 cells and their ability to grow in soft agar. These data suggest that Pim-1 overexpression may contribute to tumorigenesis in part by influencing the cellular localization and stability of p21 and by promoting cell proliferation. PMID- 17855661 TI - Mitochondria are an essential mediator of nitric oxide/cyclic guanosine 3',5' monophosphate blocking of glucose depletion induced cytotoxicity in human HepG2 cells. AB - It is well known that glucose is a major energy source in tumors and that mitochondria are specialized organelles required for energy metabolism. Previous studies have revealed that nitric oxide (NO) protects against glucose depletion induced cytotoxicity in mouse liver cells and in rat hepatocytes, but the detailed mechanism is not well understood. Therefore, we investigated the involvement of mitochondria in the NO protective effect in human hepatoma HepG2 cells. In this study, we showed that glucose depletion resulted in a time dependent decrease in intracellular NO and in the protein expression of NO synthases. This glucose depletion-induced decrease in NO was blocked by NO donors. Next, we showed that the cytoprotective effect of NO is via a cyclic guanosine 3',5'-monophosphate-dependent pathway. Additionally, SNP blocked a glucose depletion-induced decrease in mitochondrial mass, mitochondrial DNA copies, and ATP level in HepG2 cells. Moreover, glucose depletion decreased the expression of various mitochondrial proteins, including cytochrome c, complex I (NADH dehydrogenase), complex III (cytochrome c reductase), and heat shock protein 60; these glucose depletion-induced effects were blocked by SNP. Furthermore, we found that rotenone and antimycin A (mitochondria complex I and III inhibitors, respectively) blocked SNP cytoprotection against glucose depletion-induced cytotoxicity. Taken together, our results indicated that the mitochondria serve as an important cellular mediator of NO during protection against glucose deprivation-induced damage. PMID- 17855662 TI - Geldanamycin anisimycins activate Rho and stimulate Rho- and ROCK-dependent actin stress fiber formation. AB - Heat shock protein 90 (Hsp90) is a member of the heat shock family of molecular chaperones that regulate protein conformation and activity. Hsp90 regulates multiple cell signaling pathways by controlling the abundance and activity of several important protein kinases and cell cycle-related proteins. In this report, we show that inhibition of Hsp90 by geldanamycin or its derivative, 17 allylamino-17-desmethoxygeldamycin, leads to activation of the Rho GTPase and a dramatic increase in actin stress fiber formation in human tumor cell lines. Inactivation of Rho prevents geldanamycin-induced actin reorganization. Hsp90 inactivation does not alter the appearance of filopodia or lamellipodia and tubulin architecture is not visibly perturbed. Our observations suggest that Hsp90 has an important and specific role in regulating Rho activity and Rho dependent actin cytoskeleton remodeling. PMID- 17855663 TI - Ursolic acid inhibits STAT3 activation pathway leading to suppression of proliferation and chemosensitization of human multiple myeloma cells. AB - The activation of signal transducers and activators of transcription 3 (STAT3) has been linked with the proliferation of a variety of human cancer cells, including multiple myeloma. Agents that can suppress STAT3 activation have potential for prevention and treatment of cancer. In the present report, we tested an agent, ursolic acid, found in basil, apples, prunes, and cranberries, for its ability to suppress STAT3 activation. We found that ursolic acid, a pentacyclic triterpenoid, inhibited both constitutive and interleukin-6-inducible STAT3 activation in a dose- and time-dependent manner in multiple myeloma cells. The suppression was mediated through the inhibition of activation of upstream kinases c-Src, Janus-activated kinase 1, Janus-activated kinase 2, and extracellular signal-regulated kinase 1/2. Vanadate treatment reversed the ursolic acid-induced down-regulation of STAT3, suggesting the involvement of a tyrosine phosphatase. Indeed, we found that ursolic acid induced the expression of tyrosine phosphatase SHP-1 protein and mRNA. Moreover, knockdown of SHP-1 by small interfering RNA suppressed the induction of SHP-1 and reversed the inhibition of STAT3 activation, thereby indicating the critical role of SHP-1 in the action of this triterpene. Ursolic acid down-regulated the expression of STAT3-regulated gene products such as cyclin D1, Bcl-2, Bcl-xL, survivin, Mcl-1, and vascular endothelial growth factor. Finally, ursolic acid inhibited proliferation and induced apoptosis and the accumulation of cells in G1-G0 phase of cell cycle. This triterpenoid also significantly potentiated the apoptotic effects of thalidomide and bortezomib in multiple myeloma cells. Overall, these results suggest that ursolic acid is a novel blocker of STAT3 activation that may have a potential in prevention and treatment of multiple myeloma and other cancers. PMID- 17855664 TI - Increased expression of corepressors in aggressive androgen-independent prostate cancer cells results in loss of 1alpha,25-dihydroxyvitamin D3 responsiveness. AB - Vitamin D has antiproliferative activity in prostate cancer; however, resistance to vitamin D-mediated growth inhibition occurs. To investigate the mechanisms of vitamin D resistance, we screened two prostate cancer sublines of CWR22rv1, CWR22R-1, and CWR22R-2, with differential sensitivity to vitamin D. CWR22R-2 showed less response to the antiproliferative effect of vitamin D than CWR22R-1. The vitamin D receptor (VDR)-mediated transcriptional activity was also decreased in CWR22R-2. We further showed that the DNA-binding ability of VDR was decreased and the amount of NCoR in VDR response element was increased in CWR22R-2. Analysis of VDR-associated protein profiles found higher expression of the corepressors, NCoR1 and SMRT, in CWR22R-2 cells. Treatment with the histone deacetylase inhibitor, trichostatin A, increased vitamin D/VDR transcriptional activity and promoted the antiproliferative effect of vitamin D in CWR22R-2 cells. Targeted down-regulation of NCoR1 and SMRT by small interference RNA was able to restore CWR22R-2 response to vitamin D. Together, we showed that increased NCoR1 and SMRT expression in CWR22R-2 cells resulted in reduced VDR mediated transcriptional activity and attenuated antiproliferative response to vitamin D. Our data suggest that the integrity of the vitamin D/VDR-mediated signaling pathway is crucial in predicting vitamin D responsiveness and thus provide a rational design to improve vitamin D-based treatment efficacy based on molecular profiles of patients. PMID- 17855665 TI - Images in clinical medicine. Ehlers-Danlos syndrome. PMID- 17855666 TI - Putting typhoid vaccination on the global health agenda. PMID- 17855667 TI - Noroviruses--challenges to control. PMID- 17855668 TI - Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. AB - BACKGROUND: Exposure to air pollution from traffic is associated with adverse cardiovascular events. The mechanisms for this association are unknown. We conducted a controlled exposure to dilute diesel exhaust in patients with stable coronary heart disease to determine the direct effect of air pollution on myocardial, vascular, and fibrinolytic function. METHODS: In a double-blind, randomized, crossover study, 20 men with prior myocardial infarction were exposed, in two separate sessions, to dilute diesel exhaust (300 mug per cubic meter) or filtered air for 1 hour during periods of rest and moderate exercise in a controlled-exposure facility. During the exposure, myocardial ischemia was quantified by ST-segment analysis using continuous 12-lead electrocardiography. Six hours after exposure, vasomotor and fibrinolytic function were assessed by means of intraarterial agonist infusions. RESULTS: During both exposure sessions, the heart rate increased with exercise (P<0.001); the increase was similar during exposure to diesel exhaust and exposure to filtered air (P=0.67). Exercise induced ST-segment depression was present in all patients, but there was a greater increase in the ischemic burden during exposure to diesel exhaust (-22+/ 4 vs. -8+/-6 millivolt seconds, P<0.001). Exposure to diesel exhaust did not aggravate preexisting vasomotor dysfunction, but it did reduce the acute release of endothelial tissue plasminogen activator (P=0.009; 35% decrease in the area under the curve). CONCLUSIONS: Brief exposure to dilute diesel exhaust promotes myocardial ischemia and inhibits endogenous fibrinolytic capacity in men with stable coronary heart disease. Our findings point to ischemic and thrombotic mechanisms that may explain in part the observation that exposure to combustion derived air pollution is associated with adverse cardiovascular events. (ClinicalTrials.gov number, NCT00437138 [ClinicalTrials.gov].). PMID- 17855669 TI - High-dose melphalan versus melphalan plus dexamethasone for AL amyloidosis. AB - BACKGROUND: High-dose chemotherapy followed by autologous hematopoietic stem-cell transplantation has been reported to provide higher response rates and better overall survival than standard chemotherapy in immunoglobulin-light-chain (AL) amyloidosis, but these two strategies have not been compared in a randomized study. METHODS: We conducted a randomized trial comparing high-dose intravenous melphalan followed by autologous hematopoietic stem-cell rescue with standard dose melphalan plus high-dose dexamethasone in patients with AL amyloidosis. Patients (age range, 18 to 70 years) with newly diagnosed AL amyloidosis were randomly assigned to receive intravenous high-dose melphalan plus autologous stem cells or oral melphalan plus oral high-dose dexamethasone. RESULTS: Fifty patients were enrolled in each group. The results were analyzed on an intention to-treat basis, with overall survival as the primary end point. After a median follow-up of 3 years, the estimated median overall survival was 22.2 months in the group assigned to receive high-dose melphalan and 56.9 months in the group assigned to receive melphalan plus high-dose dexamethasone (P=0.04). Among patients with high-risk disease, overall survival was similar in the two groups. Among patients with low-risk disease, there was a nonsignificant difference between the two groups in overall survival at 3 years (58% in the group assigned to receive high-dose melphalan vs. 80% in the group assigned to receive melphalan plus high-dose dexamethasone; P=0.13). CONCLUSIONS: The outcome of treatment of AL amyloidosis with high-dose melphalan plus autologous stem-cell rescue was not superior to the outcome with standard-dose melphalan plus dexamethasone. (ClinicalTrials.gov number, NCT00344526 [ClinicalTrials.gov].). PMID- 17855670 TI - Idraparinux versus standard therapy for venous thromboembolic disease. AB - BACKGROUND: Venous thromboembolism is treated with unfractionated heparin or low molecular-weight heparin, followed by a vitamin K antagonist. We investigated the potential use of idraparinux, a long-acting inhibitor of activated factor X, as a substitute for standard therapy. METHODS: We conducted two randomized, open-label noninferiority trials involving 2904 patients with deep-vein thrombosis and 2215 patients with pulmonary embolism to compare the efficacy and safety of idraparinux versus standard therapy. Patients received either subcutaneous idraparinux (2.5 mg once weekly) or a heparin followed by an adjusted-dose vitamin K antagonist for either 3 or 6 months. The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolism (nonfatal or fatal). RESULTS: In the study of patients with deep venous thrombosis, the incidence of recurrence at day 92 was 2.9% in the idraparinux group as compared with 3.0% in the standard-therapy group (odds ratio, 0.98; 95% confidence interval [CI], 0.63 to 1.50), a result that satisfied the prespecified noninferiority requirement. At 6 months, the hazard ratio for idraparinux was 1.01. The rates of clinically relevant bleeding at day 92 were 4.5% in the idraparinux group and 7.0% in the standard-therapy group (P=0.004). At 6 months, bleeding rates were similar. In the study of patients with pulmonary embolism, the incidence of recurrence at day 92 was 3.4% in the idraparinux group and 1.6% in the standard-therapy group (odds ratio, 2.14; 95% CI, 1.21 to 3.78), a finding that did not meet the noninferiority requirement. CONCLUSIONS: In patients with deep venous thrombosis, once-weekly subcutaneous idraparinux for 3 or 6 months had an efficacy similar to that of heparin plus a vitamin K antagonist. However, in patients with pulmonary embolism, idraparinux was less efficacious than standard therapy. (ClinicalTrials.gov numbers, NCT00067093 [ClinicalTrials.gov] and NCT00062803 [ClinicalTrials.gov].). PMID- 17855671 TI - Extended prophylaxis of venous thromboembolism with idraparinux. AB - BACKGROUND: The extended use of vitamin K antagonists for prophylaxis against venous thromboembolism is often constrained by risk-benefit limitations and inconvenience. We evaluated the efficacy and safety of a 6-month extension of prophylaxis against recurrent venous thromboembolism with idraparinux in patients who had initially received 6 months of prophylaxis with an anticoagulant. METHODS: We randomly assigned patients who had completed 6 months of prophylaxis with idraparinux or a vitamin K antagonist and in whom extended anticoagulation was warranted to receive once-weekly injections of 2.5 mg of idraparinux or placebo for 6 months without monitoring. The primary efficacy and safety outcomes were recurrent venous thromboembolism and major bleeding. RESULTS: Of 1215 patients, 6 of 594 (1.0%) in the idraparinux group and 23 of 621 (3.7%) in the placebo group had recurrent venous thromboembolism (P=0.002). Major bleeding occurred in 11 patients (1.9%) in the idraparinux group and in none in the placebo group (P<0.001). Of these 11 episodes, 3 were fatal intracranial hemorrhages. As compared with patients whose initial treatment was a vitamin K antagonist, patients whose initial treatment was idraparinux who were assigned to 6 months in the placebo group had a lower incidence of recurrent thromboembolism (0.7% vs. 5.9%); patients who received 6 additional months of idraparinux therapy had a higher incidence of major bleeding (3.1% vs. 0.9%). CONCLUSIONS: During a 6 month extension of thromboprophylaxis, idraparinux was effective in preventing recurrent thromboembolism but was associated with an increased risk of a major hemorrhage. (ClinicalTrials.gov number, NCT00071279 [ClinicalTrials.gov].). PMID- 17855672 TI - Low-tidal-volume ventilation in the acute respiratory distress syndrome. PMID- 17855673 TI - Myocardial reperfusion injury. PMID- 17855674 TI - Images in clinical medicine. Pneumocephalus associated with pneumosinus dilatans frontalis. PMID- 17855675 TI - Case records of the Massachusetts General Hospital. Case 28-2007. A 68-year-old man with syncope. PMID- 17855676 TI - Air pollution, exercise, and cardiovascular risk. PMID- 17855677 TI - On prions, proteasomes, and mad cows. PMID- 17855678 TI - Eprodisate in AA amyloidosis. PMID- 17855679 TI - Human papillomavirus vaccine. PMID- 17855680 TI - Human papillomavirus and oropharyngeal cancer. PMID- 17855681 TI - Bariatric surgery for morbid obesity. PMID- 17855682 TI - Tetralogy of fallot in a 78-year-old man. PMID- 17855683 TI - Disappearance of antibodies to SARS-associated coronavirus after recovery. PMID- 17855684 TI - Hormones and breast cancer: what's the story? PMID- 17855685 TI - Exploring the underlying hormonal mechanisms of prenatal risk factors for breast cancer: a review and commentary. AB - Prenatal factors have been hypothesized to influence subsequent breast cancer development. Directly evaluating the associations of in utero exposures with risk, however, presents several methodologic and theoretical challenges, including the long induction period between exposure and disease and the lack of certainty regarding the critical timing of exposure. Indirect evaluation of these associations has been achieved by use of proxies such as gestational and neonatal characteristics. Evidence suggests that preeclampsia is associated with a reduced breast cancer risk, whereas high birth weight and dizygotic twinning seem associated with an increased risk. Asians born in Asia have substantially lower breast cancer risks than women born in the West. Although data thus far are few, what exists is not consistent with a unifying hypothesis for a particular biological exposure (such as estrogens or androgens) during pregnancy as mediating the observed associations between pregnancy factors and breast cancer risk. This suggests that additional studies of prenatal factors should seek to broaden the range of hormones, growth, and other endocrine factors that are evaluated in utero. Once candidate biomarkers are identified, assessing them with respect to breast cancer and with intermediate end points in carcinogenesis should be a priority. In addition, investigations should explore the possibility that in utero exposures may not act directly on the breast, but may alter other physiologic pathways such as hormone metabolism that have their effect on risk later in life. PMID- 17855686 TI - Standardization of steroid hormone assays: why, how, and when? AB - Lack of standardization of high-quality steroid hormone assays is a major deficiency in epidemiologic studies. In postmenopausal women, reported levels of serum 17beta-estradiol (E(2)) are highly variable and median normal values differ by approximately a 6-fold factor. A particular problem is the use of E(2) assays for prediction of breast cancer risk and osteoporotic fractures, where assay sensitivity may be the most important factor. Identification of women in the lowest categories of E(2) levels will likely provide prognostic information that would not be available in a large group of women in whom E(2) levels are undetectable by less sensitive assays. Detailed and costly methods involving extraction and chromatography in conjunction with RIA provide generally acceptable E(2) results in postmenopausal serum, whereas less tedious, direct immunoassays suffer from inadequate specificity and sensitivity. Studies comparing the two types of methods generally report higher E(2) values with the direct methods as a result of cross-reactivity with other steroids and reduced correlation with biological variables such as body mass index. Similar problems exist with measurements of E(2) and estrone in men, and estrone and testosterone in women. Interest in mass spectrometry-based assays is increasing as potential gold standard methods with enhanced sensitivity and specificity; however, these assays require costly instrumentation and highly trained personnel. Taking all of these issues into consideration, we propose establishment of standard pools of premenopausal, postmenopausal, and male serum, and utilization of these for cross comparison of various methods on an international basis. An oversight group could then establish standards based on these comparisons and set agreed upon confidence limits of various hormones in the pools. These criteria would allow validation of sensitivity, specificity, precision, and accuracy of current steroid hormone assay methodology and provide surrogates until a true gold standard can be developed. PMID- 17855687 TI - Plasma volume expansion in pregnancy: implications for biomarkers in population studies. AB - There is a growing body of literature focused on endogenous hormone exposures during pregnancy and subsequent cancer risk for both mother and offspring. Examples of these studies include those focused on the biological mechanism for the association of preeclampsia with reduced risk of breast cancer for mother and female offspring or studies that have examined hormone concentrations during pregnancy between different ethnic groups who vary in their rates of breast cancer incidence. Although these studies seem relatively straightforward in conception and analysis, measurement of the concentration of hormones and other biomarkers in pregnant subjects is influenced by plasma volume expansion (PVE). During pregnancy, the maternal plasma volume expands 45% on average to provide for the greater circulatory needs of the maternal organs. Consequently, serum protein and hormone concentrations are greatly altered when comparing the pregnant with nonpregnant state. Assessing PVE also is complicated by the vast individual variation in PVE, ranging from minimal to a 2-fold increase. We propose that PVE needs to be evaluated when comparing biomarker concentrations during pregnancy in two populations that may differ with respect to PVE. Small body size is associated with lower PVE compared with higher body size. Therefore, we hypothesize that variation in PVE will influence the interpretation of differences in biomarker concentrations across population groups with respect to the etiologic significance of the biomarker to the disease under study (e.g., breast cancer). It is possible that some observations may be due only to differences in dilution between the two groups. We present PVE as a topic for consideration in population-based studies, examples of the types of studies where PVE may be relevant, and our own analysis of one such study in the text below. PMID- 17855688 TI - Point: genetic risk feedback for common disease time to test the waters. PMID- 17855689 TI - Counterpoint: genetic risk feedback for common disease time to test the waters. PMID- 17855690 TI - GLIOGENE an International Consortium to Understand Familial Glioma. AB - Evidence for familial aggregation of glioma has been documented in both case control and cohort studies and occurs apart from the well-described rare inherited genetic syndromes involving glioma: neurofibromatosis type 1 and 2, tuberous sclerosis, Turcot's syndrome, and Li-Fraumeni syndrome. Nonsyndromic glioma families have been studied but no genes have been identified in the two published linkage studies of familial glioma probably due to the small number of families. Because glioma is a rare but devastating cancer, and a family history of glioma has been observed in approximately 5% of the cases, we initiated an international consortium to identify glioma families not affected by syndromes to better understand the inherited factors related to this disease. The international consortium GLIOGENE is an acronym for "glioma gene" and includes 15 research groups in North America, Europe, and Israel to study familial glioma. The overarching goal is to characterize genes in glioma families using a genome wide single-nucleotide polymorphism approach and conducting linkage analysis to identify new genomic regions or loci that could harbor genes important for gliomagenesis. Here, we review the rationale for studying familial glioma and our proposed strategy for the GLIOGENE study. PMID- 17855691 TI - Excess body weight and colorectal cancer risk in Canada: associations in subgroups of clinically defined familial risk of cancer. AB - Overweight and obesity are linked with several chronic diseases, including colorectal cancer, among men, but results among women are equivocal. Previous evidence suggests that menopausal status, postmenopausal hormone use, and family history of cancer may modify the link between adiposity and colorectal cancer. In data from two population-based case-control studies (cases: 1,292 males and 1,404 females; controls: 1,465 males and 1,203 females) in Ontario and Newfoundland, Canada, we examined the link between colorectal cancer and body mass index (BMI) at two reference periods (BMI 2 years prior and BMI at age 20 years), weight gain since age 20 years, and height. Based on recent BMI indices among men, obesity (BMI >/=30 kg/m(2)) was associated with an 80% [95% confidence interval (95% CI), 1.43-2.27] increased risk of colorectal cancer relative to a normal BMI (18.5 24.9 kg/m(2)). The same comparison for BMI at age 20 years suggested a 94% increased risk of colorectal cancer (95% CI, 1.19-3.16). Odds ratios were similar among subgroups of men with and without a clinically defined familial risk of cancer (according to the Amsterdam or revised Bethesda criteria for Lynch syndrome). Associations were moderately stronger for cancer of the colon than cancer of the rectum. Among women, BMI and weight gain were not linked with colorectal cancer; the null associations were persistent in subgroups of familial risk of cancer, menopausal status, estrogenic status, and subsite. Tall height (>1.75 m), however, was linked with increased risk of colorectal cancer among women (odds ratio, 2.27; 95% CI, 1.46-3.59) but not among men. This study suggests that obesity is associated with increased risk of sporadic and Lynch syndrome-related colon and rectal cancers among men but not among women, whereas height is directly linked with all such cancers among women but not among men. PMID- 17855692 TI - The polyp prevention trial continued follow-up study: no effect of a low-fat, high-fiber, high-fruit, and -vegetable diet on adenoma recurrence eight years after randomization. AB - The Polyp Prevention Trial (PPT) was a multicenter randomized clinical trial to evaluate the effects of a high-fiber (18 g/1,000 kcal), high-fruit and -vegetable (3.5 servings/1,000 kcal), and low-fat (20% of total energy) diet on the recurrence of adenomatous polyps in the large bowel over a period of 4 years. Although intervention participants reported a significantly reduced intake of dietary fat, and increased fiber, fruit, and vegetable intakes, their risk of recurrent adenomas was not significantly different from that of the controls. Since the PPT intervention lasted only 4 years, it is possible that participants need to be followed for a longer period of time before treatment differences in adenoma recurrence emerge, particularly if diet affects early events in the neoplastic process. The PPT-Continued Follow-up Study (PPT-CFS) was a post intervention observation of PPT participants for an additional 4 years from the completion of the trial. Of the 1,905 PPT participants, 1,192 consented to participate in the PPT-CFS and confirmed colonoscopy reports were obtained on 801 participants. The mean time between the main trial end point colonoscopy and the first colonoscopy in the PPT-CFS was 3.94 years (intervention group) and 3.87 years (control group). The baseline characteristics of 405 intervention participants and 396 control participants in the PPT-CFS were quite similar. Even though the intervention group participants increased their fat intake and decreased their intakes of fiber, fruits, and vegetables during the PPT-CFS, they did not go back to their prerandomization baseline diet (P < 0.001 from paired t tests) and intake for each of the three dietary goals was still significantly different from that in the controls during the PPT-CFS (P < 0.001 from t tests). As the CFS participants are a subset of the people in the PPT study, the nonparticipants might not be missing completely at random. Therefore, a multiple imputation method was used to adjust for potential selection bias. The relative risk (95% confidence intervals) of recurrent adenoma in the intervention group compared with the control group was 0.98 (0.88-1.09). There were no significant intervention-control group differences in the relative risk for recurrence of an advanced adenoma (1.06; 0.81-1.39) or multiple adenomas (0.92; 0.77-1.10). We also used a multiple imputation method to examine the cumulative recurrence of adenomas through the end of the PPT-CFS: the intervention-control relative risk (95% confidence intervals) for any adenoma recurrence was 1.04 (0.98-1.09). This study failed to show any effect of a low-fat, high-fiber, high-fruit and vegetable eating pattern on adenoma recurrence even with 8 years of follow-up. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1745-52). PMID- 17855693 TI - Influence of methylenetetrahydrofolate reductase gene polymorphisms C677T and A1298C on age-associated risk for colorectal cancer in a caucasian lynch syndrome population. AB - Lynch syndrome is caused by germ-line mutations in the DNA mismatch repair (MMR) genes; mutation carriers are predisposed to a variety of cancers, most commonly colorectal and endometrial. The median age of colorectal cancer onset is 45 years and the lifetime risk is approximately 80%, but the onset age varies substantially. It is likely that other low-penetrance genes and environmental factors act as modifiers of the risk associated with the highly penetrant MMR gene mutations. Methylenetetrahydrofolate reductase plays a key role in folate metabolism. We investigated the association of C677T and A1298C, two common polymorphisms in the methylenetetrahydrofolate reductase gene, with risk for early onset colorectal cancer in Lynch syndrome. Subjects were 185 non-Hispanic whites with confirmed DNA MMR mutations. Kaplan-Meier estimates for the age at colorectal cancer onset according to C677T genotypes were significantly different for the CT and TT genotypes compared with the wild-type CC (P = 0.014, log-rank test; P = 0.004, trend test). The median ages at onset were 39 [corrected] years for the CC genotype and 43 [corrected] years for the combined CT and TT [corrected] genotypes and the CT+TT [corrected] genotypes were associated with a reduced age-associated risk for developing colorectal cancer (hazard ratio, 0.55; 95% confidence interval, 0.36-0.85). No differences in ages at onset or risk were found for the A1298C genotypes. This is the first report to our knowledge to provide evidence that the C677T polymorphism modifies the age at onset of colorectal cancer in Caucasian Lynch syndrome subjects with the 677T allele having a protective effect. PMID- 17855694 TI - Carbonic anhydrase IX is highly expressed in hereditary nonpolyposis colorectal cancer. AB - Carbonic anhydrase (CA) II, CA IX, and CA XII are expressed in various neoplasias and have been linked to tumorigenesis. We examined their expression in three different groups of colorectal cancer [i.e., microsatellite stable (MSS), microsatellite instable (MSI), and hereditary nonpolyposis colorectal cancer (HNPCC)]. First, we analyzed gene expression profiles of 113 specimens by a microarray method to study the expression of various CA isozymes in the subgroups of colorectal cancer. The results indicated that mRNAs for CA II and CA XII are down-regulated and CA IX mRNA is up-regulated in all three tumor categories when compared with the normal tissue. The up-regulation of CA IX was greatest in the HNPCC group. For more information, 77 specimens were immunohistochemically stained to study the levels of CA II, CA IX, and CA XII. Immunohistochemical analyses further confirmed that the subgroups express CA II, CA IX, and CA XII differentially, and the HNPCC tumors express high levels of CA IX. Expression of these CAs did not correlate to Dukes stage or grade of differentiation. Our results show that CAs are differentially expressed in the subgroups of colorectal cancer, and CA IX expression seems to be very high in most cases of HNPCC. CA IX could be a potential diagnostic and therapeutic target in HNPCC. PMID- 17855695 TI - Effect of a 12-month exercise intervention on the apoptotic regulating proteins Bax and Bcl-2 in colon crypts: a randomized controlled trial. AB - BACKGROUND: Cellular proliferation and apoptosis (cell death) are highly regulated in the colon as insufficient apoptosis may lead to polyps and cancer. Physical activity decreases risk of colon cancer in observational studies, but the biological basis is not well defined. The objective of this study is to examine the effects of a 12-month aerobic exercise program on expression of proteins that promote (Bax) or inhibit (Bcl-2) apoptosis in colon crypts. METHODS: Two hundred two sedentary participants, 40 to 75 years, were randomly assigned to moderate-to-vigorous intensity exercise for 60 min per day, 6 days per week for 12 months, or usual lifestyle. Colon crypt samples were obtained at baseline and 12 months. Bcl-2 and Bax expression was measured by immunohistochemistry. RESULTS: Bax density at the bottom of crypts increased in male exercisers versus controls (+0.87 versus -0.18; P = 0.05), whereas the ratio of Bcl-2 to Bax at the bottom and middle of crypts decreased as aerobic fitness (VO(2)max) increased (P trend = 0.02 and 0.05, respectively). In female exercisers, Bax density in the middle of crypts decreased (-0.36 versus +0.69; P = 0.03) and Bcl-2 to Bax ratio at the top of crypts increased versus controls (+0.46 versus -0.85; P = 0.03). Bax density in the middle of crypts also decreased as minutes per week of exercise increased (P trend = 0.03). CONCLUSIONS: A 12-month exercise intervention resulted in greater expression of proteins that promote apoptosis at the bottom of colon crypts in men and decreased expression of proteins that promote apoptosis at the middle and top of colon crypts in women. The difference in effect by gender and location of observed changes warrants further study. PMID- 17855696 TI - Associations between androgen and Vitamin D receptor microsatellites and postmenopausal breast cancer. AB - We investigated the association between polymorphism in the androgen receptor (AR) and vitamin D receptor (VDR) genes and breast cancer risk in a large population-based case-control study of genetically homogenous Swedish women. We successfully determined both AR CAG(n) and VDR A(n) genotype in 1,502 women with invasive breast cancer and in 1,510 control women. We did not find any associations between AR or VDR microsatellite lengths and breast cancer when we used a priori determined cutoffs (/=22 repeats for AR and /=19 for VDR) to define long and short alleles. There was statistically significant interaction between VDR genotype and parity, such that women with two short alleles had a halved risk for breast cancer, irrespective of parity, compared with nulliparous women with two long alleles. Homozygosity for the long VDR allele was associated with a more advanced clinical stage at diagnosis. In exploratory analyses, we determined cutoffs based on visual inspection of distributions of allele lengths among cases and controls and found that women carrying two alleles with <20 AR CAG(n) repeats had an increased risk for breast cancer, odds ratio of 1.67 (95% confidence interval, 1.17-2.38), compared with those with two alleles with >/=20 repeats. Women carrying two VDR alleles with <21 A(n) were also at an increased risk, odds ratio of 1.26 (95% confidence interval, 1.04-1.51). Our data do not support major roles for AR or VDR polymorphism as breast cancer risk factors. However, we did find an interaction between VDR genotype and parity that remains to be corroborated. PMID- 17855697 TI - A prospective study of body size and breast cancer in black women. AB - The relation of body mass index (BMI) and weight gain to breast cancer risk is complex, and little information is available on Black women, among whom the prevalence of obesity is high. We assessed BMI and weight gain in relation to breast cancer risk in prospective data from the Black Women's Health Study. In 1995, 59,000 African American women enrolled in the Black Women's Health Study by completing mailed questionnaires. Data on anthropometric factors were obtained at baseline and every 2 years afterwards. In 10 years of follow-up, 1,062 incident cases of breast cancer occurred. Incidence rate ratios (IRR) were computed in multivariable Cox proportional hazards regression. BMI at age 18 years of >/=25 relative to <20 was associated with a reduced risk of breast cancer among both premenopausal women (IRR, 0.68; 95% confidence interval, 0.46-0.98) and postmenopausal women (IRR, 0.53; 95% confidence interval, 0.35-0.81). There was an inverse association of current BMI with premenopausal breast cancer but no association with postmenopausal breast cancer, either overall or among never users of hormone therapy. Weight gain was not associated with postmenopausal breast cancer risk. In analyses restricted to breast cancers that were estrogen and progesterone receptor positive, IRRs for current BMI and weight gain were elevated but not statistically significant. The findings indicate that being overweight at age 18 years is associated with a reduced risk of both premenopausal and postmenopausal breast cancer in African American women. Understanding the reasons for the association may help elucidate the pathways through which adolescent exposures influence breast cancer risk. The lack of association of obesity with receptor-negative tumors in postmenopausal African American women may partially explain why breast cancer incidence in older Black women is not high relative to other ethnic groups in spite of the high prevalence of obesity in Black women. PMID- 17855698 TI - Weight gain prior to diagnosis and survival from breast cancer. AB - BACKGROUND: To examine the effects of prediagnostic obesity and weight gain throughout the life course on survival after a breast cancer diagnosis, we conducted a follow-up study among a population-based sample of women diagnosed with first, primary invasive, and in situ breast cancer between 1996 and 1997 (n = 1,508). METHODS: In-person interviews were conducted shortly after diagnosis to obtain information on height and weight at each decade of life from age 20 years until 1 year before diagnosis. Patients were followed to determine all-cause (n = 196) and breast cancer-specific (n = 127) mortality through December 31, 2002. RESULTS: In multivariate Cox proportional hazards models, obese women had increased mortality due to breast cancer compared with ideal weight women among those who were premenopausal at diagnosis [hazard ratio (HR), 2.85; 95% confidence interval (95% CI), 1.30-6.23] and postmenopausal at diagnosis (HR, 1.91; 95% CI, 1.06-3.46). Among women diagnosed with premenopausal breast cancer, those who gained >16 kg between age 20 years and 1 year before diagnosis, compared with those whose weight remained stable (+/-3 kg), had more than a 2 fold elevation in all-cause (HR, 2.45; 95% CI, 0.96-6.27) and breast cancer specific mortality (HR, 2.09; 95% CI, 0.80-5.48). Women diagnosed with postmenopausal breast cancer who gained more than 12.7 kg after age of 50 years up to the year before diagnosis had a 2- to 3-fold increased risk of death due to all-causes (HR, 2.69; 95% CI, 1.63-4.43) and breast cancer (HR, 2.95; 95% CI, 1.36-6.43). CONCLUSIONS: These results indicate that high levels of prediagnostic weight and substantial weight gain throughout life can decrease survival in premenopausal and postmenopausal breast cancer patients. PMID- 17855699 TI - Atypia and DNA methylation in nipple duct lavage in relation to predicted breast cancer risk. AB - BACKGROUND: Tumor suppressor gene (TSG) methylation is identified more frequently in random periareolar fine needle aspiration samples from women at high risk for breast cancer than women at lower risk. It is not known whether TSG methylation or atypia in nipple duct lavage (NDL) samples is related to predicted breast cancer risk. METHODS: 514 NDL samples obtained from 150 women selected to represent a wide range of breast cancer risk were evaluated cytologically and by quantitative multiplex methylation-specific PCR for methylation of cyclin D2, APC, HIN1, RASSF1A, and RAR-beta2. RESULTS: Based on methylation patterns and cytology, NDL retrieved cancer cells from only 9% of breasts ipsilateral to a breast cancer. Methylation of >/=2 genes correlated with marked atypia by univariate analysis, but not multivariate analysis, that adjusted for sample cellularity and risk group classification. Both marked atypia and TSG methylation independently predicted abundant cellularity in multivariate analyses. Discrimination between Gail lower-risk ducts and Gail high-risk ducts was similar for marked atypia [odds ratio (OR), 3.48; P = 0.06] and measures of TSG methylation (OR, 3.51; P = 0.03). However, marked atypia provided better discrimination between Gail lower-risk ducts and ducts contralateral to a breast cancer (OR, 6.91; P = 0.003, compared with methylation OR, 4.21; P = 0.02). CONCLUSIONS: TSG methylation in NDL samples does not predict marked atypia after correcting for sample cellularity and risk group classification. Rather, both methylation and marked atypia are independently associated with highly cellular samples, Gail model risk classifications, and a personal history of breast cancer. This suggests the existence of related, but independent, pathogenic pathways in breast epithelium. PMID- 17855700 TI - Oral contraceptives and survival in breast cancer patients aged 20 to 54 years. AB - Recent oral contraceptive (OC) use is associated with modestly higher breast cancer incidence among younger women, but its impact on survival is unclear. This study examined the relationship between OC use before breast cancer diagnosis and survival. A population-based sample of 1,264 women aged 20 to 54 years with a first primary invasive breast cancer during 1990 to 1992 were followed up for 8 to 10 years. OC and covariate data were obtained by interviews conducted shortly after diagnosis and from medial records. All-cause mortality was ascertained through the National Death Index (n = 292 deaths). Age- and income-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox regression methods. All-cause mortality was not associated with ever use of OCs or duration of use. Compared with nonusers, mortality estimates were elevated among women who were using OCs at diagnosis or stopped use in the previous year (HR, 1.57; 95% CI, 0.95-2.61). The HR for use of high-dose estrogen pills within 5 years before diagnosis was double that of nonusers (HR, 2.39; 95% CI, 1.29 4.41) or, if the most recent pill included the progestin levonorgestrel, compared with nonusers (HR, 2.01; 95% CI, 1.03-3.91). Because subgroup estimates were based on small numbers of OC users, these results should be cautiously interpreted. Overall, most aspects of OC use did not seem to influence survival, although there is limited evidence that OC use just before diagnosis, particularly use of some pill types, may negatively impact survival in breast cancer patients aged 20 to 54 years. PMID- 17855701 TI - Gestational age and fetal growth in relation to maternal ovarian cancer risk in a Swedish cohort. AB - BACKGROUND: Pregnancy influences subsequent maternal ovarian cancer risk. To date, there is limited evidence whether two characteristics of pregnancy, gestational age and birth weight, could modify risk. MATERIALS AND METHODS: We studied 1.1 million Swedish women who delivered singleton births between 1973 and 2001. Information on infant gestational age and birth weight was abstracted from the nationwide Swedish Birth Register. Women were followed prospectively through linkage with other population-based registers for occurrence of ovarian cancer, death, or emigration through 2001. Hazard ratios [relative risk (RR), 95% confidence interval (95% CI)] from Cox models were used to estimate associations between gestational age, birth weight, and epithelial ovarian cancer risk. RESULTS: During 12.6 million person-years, 1,017 epithelial ovarian cancers occurred. Mean age at diagnosis was 43 years. Compared with women with term deliveries (>/=40 weeks), women with moderately (35-36 weeks) or very (<35 weeks) preterm deliveries had increased risks of epithelial ovarian cancer (RR 1.4, 95% CI 1.0-2.0 and RR 2.3, 95% CI 1.3-3.8, respectively). In contrast, women giving birth to small-for-gestational-age babies had a reduced risk (RR 0.7, 95% CI 0.4 1.0). Stratifying on birth weight and gestational age, there was a strong protective effect of low birth weight on maternal risk of epithelial ovarian cancer among term deliveries, whereas birth weight seemed to have little effect among preterm births (P(interaction) = 0.022). CONCLUSIONS: Our results lend further support that the hormonal milieu of a pregnancy may modify long-term risk of developing ovarian cancer. 32). PMID- 17855702 TI - Demographic and pathologic differences in the incidence of invasive penile cancer in the United States, 1995-2003. AB - OBJECTIVE: Penile cancer is an uncommon malignancy, so few descriptive or analytic studies have been reported in the literature. The objective of this analysis was to describe the distribution of penile cancer in the United States by demographic, pathologic, and clinical features. METHODS: Penile cancer among 6,539 men was identified through 29 population-based registries in the United States during the period 1995-2003. These registries were estimated to represent 68% of the U.S. population. Age-adjusted incidence rates were calculated per million population using counts derived from the 2000 U.S. census. A subset of nine registries was used to examine time trends in penile cancer between 1973 and 2003. RESULTS: Squamous cell carcinomas were the most common histologic type of penile cancer, representing 93% of all malignancies. Hispanic men had the highest age-adjusted incidence rates per million for penile cancer (6.58 per million), followed by Blacks (4.02 per million), Whites (3.90 per million), American Indians (2.81 per million), and Asian-Pacific Islanders (2.40 per million). The highest rates of penile cancer were found among Hispanic men (46.9 per million) and Black men (36.2 per million) of ages >/=85 years. Penile malignancy was rare among males under age 20 years. Time trend analysis supported a significant decrease in the incidence of penile cancer for Blacks (annual percent change, 1.9%) and Whites (annual percent change, -1.2%). The majority (61%) of penile cancers were diagnosed at a localized stage among all racial and ethnic groups, although Hispanic and Black men tended to be diagnosed at more advanced stages than Whites. No racial or ethnic differences in tumor grade were identified. The incidence of penile cancer was highest in the South (4.42 per million) and lowest in the West (3.28 per million) of the United States. The highest age-adjusted incidence rate was found among Black men in the South (4.77 per million) and the lowest rate among Asian-Pacific Islanders in the West (1.84 per million). CONCLUSIONS: This analysis showed significant racial/ethnic and regional variation in the incidence of penile cancer. The high rate of penile cancer among Hispanic and Southern Black men suggests differences in risk factors for this malignancy, such as circumcision, hygiene, or human papillomavirus exposure. PMID- 17855703 TI - The impact of autoimmune diseases on the incidence and prognosis of cutaneous malignant melanoma. AB - BACKGROUND: Persons being treated with IFNalpha-2b for advanced cutaneous malignant melanoma (CMM) have been reported to have a greatly improved prognosis if they develop autoantibodies or clinical signs of autoimmunity during therapy. Consequently, we examined whether autoimmune diseases might also be associated with lower CMM incidence and better prognosis. METHODS: We established a study cohort based on the entire Danish population, obtaining information on CMM and autoimmune diseases from the Danish national registers. Using log-linear regression models adjusting for age, period, and sex, we compared CMM incidence and CMM-specific mortality rates in persons with and without a history of autoimmune disease. RESULTS: Between 1977 and 2003, 20,482 cases of CMM were registered in the Danish Cancer Register. Previously diagnosed autoimmune diseases did not affect the incidence of CMM (incidence rate ratio, 1.0; 95% confidence interval, 0.9-1.1). In the first 5 years after CMM diagnosis, we observed 8,957 deaths in individuals with CMM (5,181 expected). CMM-specific mortality rates 1 to 5 years after diagnosis were similar in CMM patients with and without autoimmune diseases (mortality rate ratio, 0.9; 95% confidence interval, 0.7-1.2). CONCLUSIONS: Autoimmune conditions were not associated with CMM incidence or prognosis. The better CMM prognosis previously observed when autoantibodies or clinical signs of autoimmunity developed during IFNalpha-2b therapy may have been related to variation in individual responses to this therapy, with individuals sensitive to treatment exhibiting more signs of autoimmunity but also (independently) experiencing greater antitumor responses as a result of treatment. PMID- 17855704 TI - Cytoplasmic clusterin expression is associated with longer survival in patients with resected non small cell lung cancer. AB - BACKGROUND: Clusterin is a glycoprotein that has been implicated in many processes, including apoptosis, cell cycle regulation, and DNA repair. Previous studies have examined the prognostic value of clusterin expression in various malignancies. In the present study, we examined clusterin staining in tumors resected from patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Tumor specimens were obtained for 113 patients with completely resected NSCLC from paraffin-embedded tissue microarrays and stained with an antibody specific for clusterin. Staining patterns were observed and graded based on intensity and then correlated with clinical data. RESULTS: Positive cytoplasmic clusterin staining was observed in 44 patients, and weak/negative staining was observed in 62 patients. Patients who had tumors that stained positive for cytoplasmic clusterin had significantly longer survival in multivariate analysis (hazard ratio 0.487, 95% confidence interval 0.27-0.89). A correlation was also observed for recurrence-free survival, which approached statistical significance (hazard ratio 0.345, 95% confidence interval 0.12-1.02). In univariate analysis, patients with clusterin-positive tumors had a 63% 3-year survival, whereas patients with clusterin-negative tumors had a 42% 3-year survival (P = 0.0108); clusterin-positive tumors also had significantly less recurrence (P = 0.0231). CONCLUSIONS: Cytoplasmic clusterin staining is present in a substantial number of NSCLC tumors and may be a biomarker for longer survival in patients with surgically resected NSCLC. PMID- 17855705 TI - The association of a tobacco-specific biomarker and cigarette consumption and its dependence on host characteristics. AB - The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent carcinogen, which can be characterized by urinary concentrations of the metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-butanol (NNAL) and its glucuronide. Using baseline data in current smokers from four clinical trials, we examine the associations of urinary cotinine with CPD and of total NNAL with cotinine and the modification of these associations by several host factors. There was a linear relationship between ln(cotinine) and ln(CPD) within categories of the Fagerstrom Test of Nicotine Dependence and of age. The increasing trend was significantly smaller for subjects with high and very high nicotine addiction and for older subjects and larger in females than males. The regression of ln(total NNAL/cotinine) on ln(cotinine) declined linearly, suggesting reduced NNK uptake per unit cotinine with increasing cotinine. The decline in trend was greater in subjects with increased CPD, with greater nicotine addiction, and at older ages and was smaller in females, although gender differences were small. Variations in the ratio with host characteristics were generally similar to a recent epidemiologic analysis of effect modification of the association between lung cancer and cigarette smoking. PMID- 17855706 TI - Validation of self-reported smoking status using saliva cotinine: a rapid semiquantitative dipstick method. AB - PURPOSE: This study evaluated the performance characteristics of a novel rapid method for verifying smoking status in individuals by measurement of cotinine, the primary metabolite of nicotine, in saliva samples using an immunochromatographic strip in a "dipstick" format compared with liquid chromatography/mass spectrometry (LC/MS). MATERIALS AND METHODS: A prospective comparison was made of smoking status as determined by measurement of cotinine in urine by LC/MS (the gold standard) and in saliva using a semiquantitative dipstick assay that uses cotinine-specific monoclonal antibodies attached to gold particles and a series of avidity traps to measure cotinine levels (saliva NicAlert). One hundred seventy-two individuals from a family practice/general medical setting agreed to participate after informed consent and institutional review board approval. Saliva NicAlert tests were done by untrained operators who followed written directions. RESULTS: Comparison of smoking status as determined by urine cotinine measurement by LC/MS (50 ng/mL cutoff) with the saliva strip test results, averaged over the two operators, indicated that the saliva test strip results had a sensitivity of 99% and a specificity of 96%. Saliva NicAlert also identified four smokers who reported being nonsmokers but were confirmed to be smokers by LC/MS. CONCLUSIONS: The saliva NicAlert assay seems to be a valid, highly sensitive, and specific method for validating self-reported smoking status and may have clinical applications in selected medical settings. PMID- 17855707 TI - Dose-response modeling of occupational exposure to polycyclic aromatic hydrocarbons with biomarkers of exposure and effect. AB - In regulatory toxicology, the dose-response relationship between occupational exposure and biomarkers is of importance in setting threshold values. We analyzed the relationships between occupational exposure to polycyclic aromatic hydrocarbons (PAH) and various biomarkers of internal exposure and DNA damage with data from 284 highly exposed male workers. Personal exposure to phenanthrene and other PAHs was measured during shift and correlated with the sum of 1-, 2+9-, 3-, and 4-hydroxyphenanthrenes in post-shift urine. PAHs and hydroxyphenanthrenes were associated with DNA damage assessed in WBC as 8-oxo-7,8-dihydro-2' deoxyguanosine/10(6) dGuo and strand breaks by Comet assay as Olive tail moment. Hydroxyphenanthrenes correlated with phenanthrene (Spearman r(s) = 0.70; P < 0.0001). No correlations could be found between strand breaks and exposure (r(s) = 0.01, P < 0.0001 for PAHs; r(s) = -0.03, P = 0.68 for hydroxyphenanthrenes). Correlations with 8-oxo-7,8-dihydro-2'-deoxyguanosine/10(6) dGuo were weakly negative (r(s) = -0.22, P = 0.004 for PAHs) or flat (r(s) = -0.08, P = 0.31 for hydroxyphenanthrenes). Linear splines were applied to assess the relationships between the log-transformed variables. All regression models were adjusted for smoking and type of industry. For hydroxyphenanthrenes, 51.7% of the variance could be explained by phenanthrene and other predictors. Up to 0.77 microg/m(3) phenanthrene, no association could be found with hydroxyphenanthrenes. Above that point, hydroxyphenanthrenes increased by a factor of 1.47 under a doubling of phenanthrene exposure (slope, 0.56; 95% confidence interval, 0.47-0.64). Hydroxyphenanthrenes may be recommended as biomarker of occupational PAH exposure, whereas biomarkers of DNA damage in blood did not show a dose-response relation to PAH exposure. PMID- 17855708 TI - Serologic response to oncogenic human papillomavirus types in male and female university students in Busan, South Korea. AB - In the absence of genital samples, human papillomavirus (HPV) serology may be useful to assess HPV infection in young men and women. HPV seroprevalence and determinants of seropositivity were assessed in 817 female and 518 male university students in Busan, South Korea, of whom 74% and 44%, respectively, reported never having had penetrative sexual intercourse. Type-specific HPV DNA status, assessed by a short PCR fragment primer set, was available from genital samples. Seropositivity to L1 proteins of HPV types 16, 18, 31, 33, 45, 52, and 58 were assessed using multiplex HPV serology. Among women, HPV seroprevalence was significantly higher among sexually active (26.1%) than nonsexually active students [11.1%, odds ratio (OR) = 2.9; 95% confidence interval (95% CI), 1.8 4.7], although the association was weaker than that for HPV DNA prevalence (OR, 14; 95% CI, 4.7-42). Furthermore, HPV seroprevalence was higher among HPV DNA positive (24%) than HPV DNA-negative women (13%), and there was a positive correlation of type-specific seroprevalence with the presence of HPV DNA of the same type. In contrast, HPV seropositivity among men was not associated with sexual behavior or the presence of HPV DNA. Seroprevalence correlates with genital HPV exposure in young women, but its meaning in young men is unclear. PMID- 17855709 TI - Adiposity and sex hormones in girls. AB - Greater body fatness during childhood is associated with reduced risk of premenopausal breast cancer, but few studies have addressed the relation of adiposity with sex hormones in girls. We prospectively examined associations between adiposity and circulating levels of sex hormones and sex hormone-binding globulin (SHBG) among 286 girls in the Dietary Intervention Study in Children. Participants were 8 to 10 years old at baseline and were followed for an average of 7 years. Anthropometric measurements were taken at baseline and at subsequent annual visits, and blood samples were collected every 2 years. Concentrations of dehydroepiandrosterone sulfate (DHEAS) during follow-up were higher among girls with greater body mass index (BMI) at baseline. The mean for the lowest BMI quartile was 63.0 microg/dL compared with 78.8 microg/dL for the highest quartile, and each kg/m(2) increment in baseline BMI was associated with a 4.3% increase (95% confidence interval, 1.6-7.0%) in DHEAS levels during follow-up (P(trend) = 0.002). Concentrations of SHBG during follow-up were lower among girls with greater BMI at baseline. The mean for the lowest BMI quartile was 94.8 nmol compared with 57.5 nmol for the highest quartile, and each kg/m(2) increment in baseline BMI was associated with an 8.8% decrease (95% confidence interval, 7.0-10.6%) in SHBG levels during follow-up (P(trend) < 0.0001). Estrogen and progesterone concentrations were similar across BMI quartiles. These findings suggest that adiposity may alter DHEAS and SHBG levels in girls. Whether and how these differences affect breast development and carcinogenesis requires further research. PMID- 17855710 TI - Serum 25(OH)-vitamin D concentration and risk of esophageal squamous dysplasia. AB - BACKGROUND: Squamous dysplasia is the precursor lesion for esophageal squamous cell carcinoma, and nutritional factors play an important role in the etiology of this cancer. Previous studies using a variety of measures for vitamin D exposure have reached different conclusions about the association between vitamin D and the risk of developing esophageal cancer. METHODS: We measured serum 25 hydroxyvitamin D [25(OH)D] concentrations in a cross-sectional analysis of 720 subjects from Linxian, China, a population at high risk for developing esophageal squamous cell carcinoma. All subjects underwent endoscopy and biopsy and were categorized by the presence or absence of histologic squamous dysplasia. We used crude and multivariate-adjusted generalized linear models to estimate the relative risks (RR) and 95% confidence intervals (95% CI) for the association between squamous dysplasia and sex-specific quartiles of serum 25(OH)D concentration. RESULTS: Two-hundred and thirty of 720 subjects (32%) had squamous dysplasia. Subjects with dysplasia had significantly higher median serum 25(OH)D concentrations than subjects without dysplasia, 36.5 and 31.5 nmol/L, respectively (Wilcoxon two-sample test, P = 0.0004). In multivariate-adjusted models, subjects in the highest compared with the lowest quartiles were at a significantly increased risk of squamous dysplasia (RR, 1.86; 95% CI, 1.35-2.62). Increased risks were similar when examined in men and women separately: men (RR, 1.74; 95% CI, 1.08-2.93); women (RR, 1.96; 95% CI, 1.28-3.18). CONCLUSIONS: Higher serum 25(OH)D concentrations were associated with significantly increased risk of squamous dysplasia. No obvious source of measured or unmeasured confounding explains this finding. PMID- 17855711 TI - Early onset pancreatic cancer: evidence of a major role for smoking and genetic factors. AB - Pancreatic cancer ranks 4th as a cause of cancer mortality and in approximately 5% to 10% of patients, this lethal tumor develops before age 50. We used age-, sex-, and country-specific cancer incidence and mortality data to describe the burden of early onset pancreatic cancer (EOPC) worldwide. We also reviewed the current published evidence on smoking and genetic factors associated with EOPC. We found an excess of EOPC resulting in a substantial number of years-of-life lost in countries from Central and Eastern Europe. Worldwide, the proportion of EOPC is strongly correlated with lung cancer mortality (R(2) = 0.53), suggesting that approximately half of the variation in the proportion of EOPC could be explained by smoking. The unusual pattern of the incidence of pancreatic cancer by gender and race supports the primary role of smoking in the etiology of EOPC: the excess male-to-female rate ratio, attributable mainly to smoking, gradually approaches unity with increasing age. Moreover, male-to-female rate ratios are greater in blacks than in whites only in younger patients. Published studies also identified genetic alterations involved either alone or in association with smoking in the development of EOPC. In conclusion, EOPC constitutes only 1% to 5% of the total deaths from pancreatic cancer worldwide, but is responsible for 20% to 30% of the total number of years-of-life-lost caused by the disease. Smoking and genetic mutations are the major identified risk factors and seem to be even more important for EOPC than for PC in older age groups. PMID- 17855712 TI - Detection of cotinine in newborn dried blood spots. AB - Maternal smoking while pregnant is a plausible risk factor for childhood cancers because many seem to initiate in utero and tobacco-specific carcinogens cross the placenta. Social desirability bias may affect maternal report of smoking in case control studies and could explain inconsistently observed associations with offspring cancer. Detection of tobacco smoke biomarkers in dried blood spots (DBS), which are increasingly stored by newborn screening programs, may improve retrospective assessment of fetal tobacco exposure. As proof-of-principle, we examined cotinine in DBS of 20 infants enrolled in a pilot study of pregnancy among low-income women. We recruited 107 pregnant women (<30 weeks of gestation) from six Women, Infants, and Children clinics in Minneapolis and St. Paul in 1999. Blood samples obtained at enrollment were tested for total cotinine using gas chromatography/mass spectrometry. Women were then interviewed at 7 months of gestation to determine current smoking habits. DBS were obtained from the Minnesota Department of Health. We tested DBS from 10 infants whose mothers had detectable serum cotinine at baseline and 10 control infants whose mothers had none. One quarter of each DBS was assayed for cotinine using gas chromatography/mass spectrometry; levels were estimated assuming 50 muL blood per sample. Mean cotinine was 29 ng/mL (SD, 7.5), 45 ng/mL (SD, 9.7), and 9 ng/mL (SD, 7.4), respectively, among infants of all smokers, infants of four women who acknowledged smoking at 7 months of gestation, and infants of nonsmokers. These results suggest that DBS analysis may identify infants of women who smoke throughout pregnancy. PMID- 17855713 TI - Noninvasive prediction of prostatic DNA damage by oxidative stress challenge of peripheral blood lymphocytes. AB - To move closer to the goal of individualized risk prediction for prostate cancer, we used an in vivo canine model to evaluate whether the susceptibility of peripheral blood lymphocytes (PBLs) to oxidative stress-induced DNA damage could identify those individuals with the highest prostatic DNA damage. This hypothesis was tested in a population of 69 elderly male beagle dogs after they had completed a 7-month randomized feeding trial to achieve the broad range of dietary selenium status observed in U.S. men. The alkaline Comet assay was used to directly compare the extent of DNA damage in PBLs with prostatic DNA damage in each dog. Using stepwise logistic regression, the sensitivity of PBLs to oxidative stress challenge with hydrogen peroxide (H(2)O(2)) predicted dogs in the highest tertile of prostatic DNA damage. Dogs with PBLs highly sensitive to H(2)O(2) were 7.6 times [95% confidence interval (95% CI), 1.5-38.3] more likely to have high prostatic DNA damage than those in the H(2)O(2)-resistant group. This risk stratification was observed in multivariate analysis that considered other factors that might influence DNA damage, such as age, toenail selenium concentration, and serum testosterone concentration. Our data show that the sensitivity of PBLs to oxidative stress challenge, but not endogenous DNA damage in PBLs, provides a noninvasive surrogate marker for prostatic DNA damage. These findings lend support to the concept that oxidative stress contributes to genotoxic damage, and that oxidative stress challenge may stratify men for prostate cancer risk. PMID- 17855714 TI - Hormone-metabolizing genotypes: an alternate interpretation. PMID- 17855715 TI - Charting a strategic direction for the American Society of Preventive Oncology's Survivorship Interest Group. PMID- 17855716 TI - American health policy: cracks in the foundation. AB - Much American health policy over the past thirty-five years has focused on reducing the additional health care that is consumed when a person becomes insured, that is, reducing moral hazard. According to conventional theory, all of moral hazard represents a welfare loss to society because its cost exceeds its value. Empirical support for this theory has been provided by the RAND Health Insurance Experiment, which found that moral hazard--even moral hazard in the form of effective and appropriate hospital procedures--could be reduced substantially using cost-sharing policies with little or no measurable effect on health. This article critically analyzes these two cornerstones of American health policy. It holds that a large portion of moral hazard actually represents health care that ill consumers would not otherwise have access to without the income that is transferred to them through insurance. This portion of moral hazard is efficient and generates a welfare gain. Further, it holds that the RAND experiment's finding (that health care could be reduced substantially with little or no effect on health) may actually be caused by the large number of participants who voluntarily dropped out of the cost-sharing arms of the experiment. Indeed, almost all of the reduction in hospital use in the cost sharing plans could be attributed to this voluntary attrition. If so, the RAND finding that cost sharing could reduce health care utilization, especially utilization in the form of effective and appropriate hospital procedures, with no appreciable effect on health is spurious. The article concludes by observing that the preoccupation with moral hazard is misplaced and has worked to obscure policies that would better reduce health care expenditures. It has also led us away from policies that would extend insurance coverage to the uninsured. PMID- 17855717 TI - Litigating the science of breast cancer treatment. AB - Beginning in the late 1980s, many health insurers refused to cover high-dose chemotherapy with autologous bone marrow transplant (HDC/ABMT) for high-risk and metastatic breast cancer patients. Insurers denied coverage because there was no persuasive evidence of clinical effectiveness. In response, many women sued to compel coverage. After years of litigation and the expenditure of approximately $3 billion, randomized clinical trials (RCTs) showed that the procedure was no more effective and possibly more harmful than conventional therapy. To understand whether and how litigation contributed to the diffusion of the procedure, we conducted a series of case studies that examine the litigation tactics and strategies used by defense and plaintiffs' counsel. Despite the fact that HDC/ABMT lacked proven scientific effectiveness, insurance defense attorneys were unable to stop the procedure's diffusion. Plaintiffs' attorneys had a much easier and more sympathetic story to tell and were able to exploit vulnerabilities facing the defense. PMID- 17855718 TI - The impact of the adoption of gag laws on trust in the patient-physician relationship. AB - Physician organizations, policy makers, and patient advocates have expressed concern that health plans have contractually limited the freedom of physicians to communicate with their patients. In response, many states have adopted gag laws that limit the ability of managed care contracts to restrict patient-physician communication. We examine the impact of these laws on patient trust in the physician. We analyzed patients' ratings of trust in their physicians in states before and after adoption of gag laws. Individuals in states that had such laws throughout the study period were used as the comparison group. The analysis is based on a nationally representative sample of adults obtained from the 1996-1997 and 1998-1999 Community Tracking Study Household Surveys. After adjustment for patient characteristics, it was estimated that the adoption of gag laws had no statistically significant impact on trust in the physician for the average patient. However, the adoption of gag laws is estimated to have increased trust in the physician by a modest amount (25 percent of a standard deviation) for health maintenance organization (HMO) enrollees who did not have a usual source of care. Gag laws may assure HMO enrollees without a usual source of care that their physicians are free to speak candidly about treatment options. This does not necessarily imply that physicians are prohibited from speaking freely in the absence of such laws, but gag laws indicate concerns (justified or not) that patients have about unrestricted communication with their health care providers. PMID- 17855719 TI - Medical malpractice reform and insurer claims defense: unintended effects? AB - In response to recent and past medical malpractice insurance crises, most states have implemented reforms meant to stabilize premiums and coverage availability. The importance of understanding whether these reforms implicitly affect the behavior and incentives of plaintiffs, attorneys, medical providers, and malpractice insurers in the intended way is crucial to policy makers, if they are to achieve their goal. This study specifically examines the effect of reforms on the claims defense efforts of insurers, given that defense expenses account for approximately 30 percent of malpractice premiums. Using state data for the period 1998-2002, we regress claims defense expenses against a variety of reform variables. These include seven tort reforms (noneconomic damage caps, punitive damage limits, attorney fee limits, modified collateral source rule, modified joint and several liability doctrine, mandatory pretrial screening, and statute of limitations) and two government-sponsored insurance mechanisms (joint underwriting associations and patient compensation funds). Claims defense expenses are found to be higher in the presence of noneconomic damage caps, punitive damage limits, and attorney fee limits--an unintended and counterproductive effect of reform--but are lower with mandatory pretrial screening and patient compensation funds. PMID- 17855720 TI - Sanctions and recidivism: an evaluation of physician discipline by state medical boards. AB - This article descriptively assesses how physicians are disciplined by state medical boards throughout the United States, drawing on a nationwide database of sanctions delivered during the period 1994-2002. We identify the frequency and severity of disciplinary actions, the offenses leading to actions, and the degree to which sanctioned physicians are subsequently sanctioned again in the future. The most significant finding is that there are a very large number of repeat offenders among physicians who have received board sanctions, indicating a possible need for greater monitoring of disciplined physicians or less reliance upon rehabilitative sanctions. PMID- 17855721 TI - Evidence for impaired long-term potentiation in schizophrenia and its relationship to motor skill learning. AB - Several lines of evidence suggest that schizophrenia (SCZ) is associated with disrupted plasticity in the cortex. However, there is little direct neurophysiological evidence of aberrant long-term potentiation (LTP)-like plasticity in SCZ and little human evidence to establish a link between LTP to learning and memory. LTP was evaluated using a neurophysiological paradigm referred to as paired associative stimulation (PAS). PAS involves pairing of median nerve electric stimulation with transcranial magnetic stimulation (TMS) over the contralateral motor cortex (for abductor pollicis brevis muscle activation) delivered at 25-ms interstimulus interval. This pairing was delivered at a frequency of 0.1 Hz for 30 min. LTP was reflected by the change in motor evoked potentials (MEPs) before and after PAS. In addition, motor skill learning was assessed using the rotary pursuit task. Compared with healthy subjects, patients with SCZ demonstrated significant MEP facilitation deficits following PAS and impaired rotary-pursuit motor learning. Across all subjects there was a significant association between LTP and motor skill learning. These data provide evidence for disrupted LTP in SCZ, whereas the association between LTP with motor skill learning suggests that the deficits in learning and memory in SCZ may be mediated through disordered LTP. PMID- 17855722 TI - Prolonged treatment of Salmonella enterica serovar Typhimurium with commercial disinfectants selects for multiple antibiotic resistance, increased efflux and reduced invasiveness. AB - OBJECTIVES: To study how disinfectants affect antimicrobial susceptibility and phenotype of Salmonella enterica serovar Typhimurium SL1,344. METHODS: Wild-type strain SL1,344 and its isogenic gyrA mutant were passaged daily for 7 days in subinhibitory concentrations, and separately for 16 days in gradually increasing concentrations of a quaternary ammonium disinfectant containing formaldehyde and glutaraldehyde (QACFG), an oxidizing compound blend (OXC), a phenolic tar acids based disinfectant (TOP) and triclosan. The MICs of antimicrobials and antibiotics for populations and representative isolates and the proportion of cells resistant to the MICs for the wild-type were determined. Expression of acrB gene, growth at 37 degrees C and invasiveness of populations in Caco-2 intestinal epithelial cells were assessed. RESULTS: QACFG and triclosan showed the highest selectivity for variants with reduced susceptibility to chloramphenicol, tetracycline, ampicillin, acriflavine and triclosan. Populations treated with the above biocides had reduced invasiveness in Caco-2 cells, and altered growth kinetics. Resistance to disinfectants was observed only after exposure to gradually increasing concentrations of triclosan, accompanied with a 2000-fold increase in its MIC. Growth in OXC and TOP did not affect the MICs of antibiotics, but resulted in the appearance of a proportion of cells resistant to the MIC of acriflavine and triclosan for the wild-type. Randomly selected stable variants from all populations, except the one treated with TOP, over-expressed acrB. CONCLUSIONS: In vitro exposure to QACFG and triclosan selects for Salmonella Typhimurium cells with reduced susceptibility to several antibiotics. This is associated with overexpression of AcrAB efflux pump, but accompanied with reduced invasiveness. PMID- 17855723 TI - Demonstration of in vivo transfer of doxycycline resistance mediated by a novel transposon. AB - OBJECTIVES: The aim of this study was to investigate the transfer of bacterial doxycycline resistance between oral bacteria in subjects receiving systemic doxycycline for the treatment of periodontitis. PATIENTS AND METHODS: Streptococci were cultured before and after treatment from the subgingival plaque of two patients with periodontitis, genotyped and investigated for the presence of antimicrobial resistance determinants and conjugative transposons. RESULTS: In one subject, a strain of Streptococcus sanguinis resistant to doxycycline was a minor component of the pre-treatment streptococcal flora but dominated post treatment. In a second subject, a strain of Streptococcus cristatus, which was sensitive to doxycycline before treatment, was found to have acquired a novel conjugative transposon during treatment, rendering it resistant to doxycycline and erythromycin. The novel transposon, named CTn6002, was sequenced and found to be a complex element derived in part from Tn916, and an unknown element which included the erythromycin resistance gene erm(B). A strain of Streptococcus oralis isolated from this subject pre-treatment was found to harbour CTn6002 and was therefore implicated as the donor. CONCLUSIONS: This is the first direct demonstration of transfer of antimicrobial resistance carried on a conjugative transposon between oral bacteria during systemic antimicrobial treatment of periodontitis in humans. PMID- 17855724 TI - Antimicrobial susceptibility among organisms from the Asia/Pacific Rim, Europe and Latin and North America collected as part of TEST and the in vitro activity of tigecycline. AB - OBJECTIVES: To describe antimicrobial susceptibility among bacterial isolates associated with hospital infections collected from 266 centres in Asia/Pacific Rim (n = 1,947), North America (n = 24,283), Latin America (n = 1,957) and Europe (n = 8,796). METHODS: Isolates were collected from blood, respiratory tract, urine, skin, wound, body fluids and other defined sources between January 2004 and August 2006. Only one isolate per patient was accepted. In vitro MICs for the isolates were determined according to the CLSI (formerly NCCLS) guidelines. RESULTS: Key organisms collected were Acinetobacter baumannii (n = 2,902), Enterobacter spp. (n = 5,731), Escherichia coli (n = 6,504), Klebsiella pneumoniae (n = 4,916), Pseudomonas aeruginosa (n = 5,128), Serratia marcescens (n = 2,313), Enterococcus faecalis (n = 2,701), Enterococcus faecium (n = 1,035) and Staphylococcus aureus (n = 5,753). Rates of methicillin resistance among S. aureus and of vancomycin resistance among enterococci were highest in North America (2,016/3,809, 52.9% and 571/2,544, 22.4%, respectively) and lowest in Europe (337/1,340, 25.1% and 36/916, 3.9%, respectively). Tigecycline was the only antimicrobial to maintain activity against all Gram-positive isolates (MIC(90) values of 93% susceptibility in all regions) antimicrobials against the Gram negative species, except for A. baumannii and P. aeruginosa. Piperacillin/tazobactam and amikacin were the most active against P. aeruginosa. Extended-spectrum beta-lactamase producers among K. pneumoniae occurred most frequently in Latin America (124/282, 44.0%). CONCLUSIONS: Tigecycline is a novel broad-spectrum antimicrobial that is active against the common organisms associated with infections. PMID- 17855725 TI - Pharmacokinetics of voriconazole during continuous venovenous haemodiafiltration. AB - OBJECTIVES: Voriconazole is a new triazole antifungal agent that is frequently used in intensive care patients with severe fungal infections. Continuous venovenous haemodiafiltration (CVVHDF) is an important extracorporal renal replacement therapy in critically ill patients suffering from severe infections and multiple organ failure. This study investigates the pharmacokinetics of voriconazole in anuric patients undergoing CVVHDF. PATIENTS AND METHODS: Pharmacokinetic analysis was performed in nine intensive care patients-one of them with liver cirrhosis-with suspected or proven fungal infection and acute renal failure undergoing CVVHDF who received voriconazole intravenously. The concentration of voriconazole in serum and ultradiafiltrate was determined by HPLC. RESULTS: Mean peak pre-filter voriconazole concentration in eight patients without cirrhosis was 5.9 +/- 2.9 mg/L and mean pre-filter trough level was 1.1 +/- 0.3 mg/L. Mean elimination half-life, mean volume of distribution, mean AUC(0 12) and mean sieving coefficient were 14.7 +/- 6.5 h, 228 +/- 42 L, 22.4 +/- 3.7 mg.h/L and 0.56 +/- 0.16, respectively. The total clearance was 12.9 +/- 6.7 L/h and the clearance via CVVHDF was 1.1 +/- 0.3 L/h. In the patient with liver cirrhosis, elimination half-life, volume of distribution, AUC(0-12) and sieving coefficient were 52 h, 301 L, 19.8 mg.h/L and 0.31, respectively. CONCLUSIONS: Voriconazole should be given without a dosage adaptation in critically ill patients without liver cirrhosis undergoing CVVHDF. However, according to results in one patient, reduction of the maintenance dosing regimen of voriconazole seems to be meaningful in patients with liver cirrhosis. PMID- 17855726 TI - Characterization of CTX-M and SHV extended-spectrum beta-lactamases and associated resistance genes in Escherichia coli strains of food samples in Tunisia. AB - OBJECTIVES: To assess the occurrence of extended-spectrum beta-lactamases (ESBLs) in Escherichia coli isolates of faecal samples of animals (n = 40) and food samples (n = 38) obtained in Tunisia in 2006, and to characterize the type of ESBLs, their genetic environments and the associated resistance genes. METHODS: Samples were inoculated in supplemented media (2 mg/L cefotaxime) for isolation of broad-spectrum cephalosporin-resistant E. coli isolates (one isolate/sample). ESBLs and their genetic environments as well as integrons and their gene cassette composition were characterized by PCR and sequencing. RESULTS: ESBL-producing E. coli isolates were detected in 10 of the 38 food samples analysed (26%) and in none of the tested animal faecal samples. Genes found were as follows (number of isolates): bla(CTX-M-1) (5), bla(CTX-M-1) + bla(TEM-1b) (1), bla(CTX-M-14) + bla(TEM-1b) (2), bla(CTX-M-8) (1) and bla(SHV-5) (1). All ESBL-positive isolates showed unrelated PFGE patterns. ISEcp1 and IS903 were detected surrounding bla(CTX-M-14), and ISEcp1/IS26 and orf477 surrounding some of the bla(CTX-M-1) genes. Four of the ESBL-positive strains harboured class 1 integrons including different gene cassette combinations. CONCLUSIONS: ESBLs, mainly of the CTX-M class, are detected in E. coli of food origin in Tunisia, being the first time that this mechanism has been detected in food E. coli strains in Africa. PMID- 17855727 TI - Efficacy of posaconazole and amphotericin B in experimental invasive pulmonary aspergillosis in dexamethasone immunosuppressed rats. AB - OBJECTIVES: Invasive pulmonary aspergillosis is associated with high mortality. To assess new antifungal therapy options, animal models have to be developed to assess, in an appropriate setting, the activity of new drugs. METHODS: Male albino CD rats (125-150 g) were fed with a protein-free diet and received dexamethasone thrice weekly subcutaneously during the whole experiment. After 2 weeks, an inoculum of 10(6) conidia of Aspergillus fumigatus (H11-20) was injected intratracheally. Antifungal treatment was initiated and continued for a total of 7 days. Animals were grouped in numbers of 10. One group of animals served as untreated control, whereas the others were treated with amphotericin B intraperitoneally (2 and 4 mg/kg) and posaconazole via gavage (2, 4, 10 and 20 mg/kg). Survival and log(10) cfu/g of the lungs were the endpoints. The strain H11-20 was tested for susceptibility in vitro to amphotericin B and posaconazole, respectively. Fungal burden of the lungs was expressed as log(10) cfu/g. Survival analysis was performed by the Kaplan-Meier method. Differences in fungal burden were assessed by the Mann-Whitney test. RESULTS: All untreated animals died within a week. Amphotericin B and posaconazole at 2 mg/kg demonstrated survival benefits over control (P = 0.01 and P = 0.04). Dosages of 4 mg/kg were superior to 2 mg/kg for amphotericin B (P = 0.02) and posaconazole (P < 0.05), respectively. No further survival benefits were demonstrated beyond dosages of 10 mg/kg. Rats treated with 20 mg/kg posaconazole, however, had a lower fungal burden than all the other treatment groups (P = 0.0002). CONCLUSIONS: Posaconazole and amphotericin B are effective in a dosage-dependent manner in this pulmonary aspergillosis model in immunocompromised rats. PMID- 17855728 TI - Prevalence and predictors of significant sleep disturbances in children undergoing ambulatory tonsillectomy and adenoidectomy. AB - OBJECTIVE: To evaluate children's sleep patterns before and after ambulatory surgery and to identify predictors of sleep decrements following surgery. METHODS: Participants were 55, 6- to 12-year-old children undergoing tonsillectomy and adenoidectomy. Sleep was assessed using actigraphy for 5 nights prior to and 5 nights following surgery. Parent state and trait anxiety, and child perioperative anxiety and temperament were assessed. Data on postoperative pain and use of analgesics were collected. RESULTS: Children had significantly less efficient sleep following surgery than before surgery. Approximately one third of children demonstrated clinically significant decrements in sleep efficiency. Discriminant function analysis indicated less sociable and more anxious children were more likely to experience these sleep decrements, as were children who experienced greater pain in the postoperative period. CONCLUSION: Children's sleep is an important consideration in recovery from surgery and this article takes a first step toward identifying predictors of the development of clinically significant sleep disruptions following surgery. PMID- 17855729 TI - A kinesin is present at unique sertoli/spermatid adherens junctions in rat and mouse testes. AB - During spermatogenesis, spermatids undergo a "down and up" translocation event in the seminiferous epithelium. This event has been proposed to result from the movement of ectoplasmic specializations, which are formed in Sertoli cells at sites of adhesion to spermatids, along adjacent microtubule tracts. To test the hypothesis that a kinesin is associated with ectoplasmic specializations, we generated antibodies to conserved kinesin sequences and detected kinesins on fixed frozen testis sections and fixed seminiferous epithelial fragments. The antibodies reacted with ectoplasmic specializations related to spermatids, in addition to reacting with other structures in the epithelium known to contain kinesins. At the electron microscopy level, the antibodies reacted with the cytoplasmic face of the endoplasmic reticulum component of ectoplasmic specializations. Based on mRNA transcript screens using mouse GeneChip arrays of testis and Sertoli cells, we identified KIF20 as a candidate kinesin at ectoplasmic specializations. Antibodies generated against a peptide sequence unique to this kinesin reacted at ectoplasmic specializations in testis sections and epithelial fragments, as well as with the endoplasmic reticulum component of ectoplasmic specializations when analyzed by electron microscopy. The antibody reacted on Western blots with full-length KIF20. On Western blots of testis lysates, the antibody reacted with a protein that is not present in other tissues and which migrates at a higher molecular weight than that predicted for KIF20. Our results demonstrate that a kinesin is associated with apical ectoplasmic specializations in Sertoli cells and that the motor may be an isoform of KIF20. PMID- 17855730 TI - Galectin 15 (LGALS15): a gene uniquely expressed in the uteri of sheep and goats that functions in trophoblast attachment. AB - Galectins are a family of secreted animal lectins with biological roles in cell adhesion and migration. In sheep, galectin 15 (LGALS15) is expressed specifically in the endometrial luminal (LE) and superficial glandular (sGE) epithelia of the uterus in concert with blastocyst elongation during the peri-implantation period. The present study examined LGALS15 expression in the uterus of cattle, goats, and pigs. Although the bovine genome contains an LGALS15-like gene, expressed sequence tags encoding LGALS15 mRNA were found only for sheep, and full-length LGALS15 cDNAs were cloned only from endometrial total RNA isolated from pregnant sheep and goats, but not pregnant cattle or pigs. Ovine and caprine LGALS15 were highly homologous at the mRNA (95%) and protein (91%) levels, and all contained a conserved carbohydrate recognition domain and RGD recognition sequence for integrin binding. Endometrial LGALS15 mRNA levels increased after Day 11 of both the estrous cycle and pregnancy, and were considerably increased after Day 15 of pregnancy in goats. In situ hybridization detected abundant LGALS15 mRNA in endometrial LE and sGE of early pregnant goats, but not in cattle or pigs. Immunoreactive LGALS15 protein was present in endometrial epithelia and conceptus trophectoderm of goat uteri and detected within intracellular crystal structures in trophectoderm and LE. Recombinant ovine and caprine LGALS15 proteins elicited a dose-dependent increase in ovine trophectoderm cell attachment in vitro that was comparable to bovine fibronectin. These results support the hypothesis that LGALS15 is uniquely expressed in Caprinae endometria and functions as an attachment factor important for peri-implantation blastocyst elongation. PMID- 17855731 TI - Out of the dark: how the PIFs are unmasking a dual temporal mechanism of phytochrome signalling. AB - Following light-induced nuclear translocation, the phytochromes induce changes in gene expression to regulate plant development. PIF3 and other PIFs (phytochrome interacting factors), members of the bHLH (basic helix-loop-helix) family of transcriptional regulators, interact specifically with the active Pfr conformer of the phytochrome molecule, suggesting that the PIFs are key components of phytochrome signal transduction. The mechanism by which the PIFs transduce phytochrome signals is not understood. After initial studies that suggested that PIF3 was a positive regulator of phytochrome signalling, mutant studies indicated that the PIFs primarily act as negative regulators in the pathway. Furthermore, in some cases they accumulate in the dark and are degraded upon illumination by the ubiquitin-26S proteasome system. At least for PIF3, the protein degradation depends on direct interaction with the phytochrome molecule and is preceded by protein phosphorylation. In this review, the current understanding of the role of the PIFs in phytochrome-mediated photomorphogenesis will be summarized, and recent findings suggesting an unanticipated dual mechanism of action of the PIFs will be discussed. PMID- 17855732 TI - Genetic diversity in a feral horse population from Sable Island, Canada. AB - The present-day Sable Island horse population, inhabiting an island off the eastern coast of Canada, is believed to have originated mainly from horses confiscated from the early French settlers in Nova Scotia in the latter half of the 18th century. In 1960, the Sable Island horses were given legal protected status and no human interference has since been allowed. The objective of this study was to characterize the current genetic diversity in Sable Island horses in comparison to 15 other horse breeds commonly found in Canada and 5 Spanish breeds. A total of 145 alleles from 12 microsatellite loci were detected in 1093 horses and 40 donkeys. The average number of alleles per locus ranged from 4.67 in the Sable Island horse population to 8.25 in Appaloosas, whereas the mean observed heterozygosity ranged from 0.626 in the Sable Island population to 0.787 in Asturcons. Various genetic distance estimates and clustering methods did not permit to support that the Sable Island horses originated from shipwrecked Spanish horses, according to a popular anecdote, but closely resemble light draft and multipurpose breeds commonly found in eastern Canada. Based on the Weitzman approach, the loss of the Sable Island horse population to the overall diversity in Canada is comparable or higher than any other horse breed. The Sable Island horse population has diverged enough from other breeds to deserve special attention by conservation interest groups. PMID- 17855733 TI - Genotoxicity assessment in oncology nurses handling anti-neoplastic drugs. AB - Many anti-neoplastic drugs are used globally during chemotherapy in the treatment of cancer. However, occupational exposure to anti-cancer drugs can represent a potential health risk to humans. Investigations on the genotoxicity of these drugs are inconsistent. Further, information on the genotoxic potential of anti neoplastic drugs in medical personnel from India is not available. Hence, the aim of this study was to carry out genotoxicity monitoring of nurses from the oncology department of a hospital in South India, occupationally exposed to anti neoplastic drugs under routine working conditions. The level of genome damage was determined in whole blood with the comet assay as well as micronucleus test (MNT) and in buccal epithelial cells with MNT alone of 60 nurses handling anti neoplastic drugs and 60 referents matched for age and sex. Urinary cyclophosphamide (CP), used as a marker for drug absorption, was also measured in the urine of the nurses. The DNA damage observed in the lymphocytes of exposed nurses was significantly higher than the controls. Similarly, a significant increase in micronuclei (MN) frequency with peripheral blood lymphocytes and buccal cells was observed in the exposed nurses compared to controls (P < 0.05). Multiple regression analysis showed that occupational exposure and age had a significant effect on mean comet tail length as well as on frequency of MN. The mean value of CP in urine of the nurses handling anti-neoplastic drugs was (mean +/- standard deviation; 0.44 +/- 0.26 microg/ml). Our study has shown that increased genetic damage was evident in nurses due to occupational exposure to anti-neoplastics. This data corroborate the need to maintain safety measures to avoid exposure and the necessity of intervention in the case of exposure when using and handling anti-neoplastic drugs. PMID- 17855734 TI - Characterization of the genotoxic potential of formaldehyde in V79 cells. AB - Formaldehyde (FA) is known to be genotoxic and mutagenic in proliferating mammalian cells in vitro. The present study was performed to further characterize its genotoxic potential in the V79 Chinese hamster cell line. The induction of DNA strand breaks and DNA-protein cross-links (DPXs) was measured by the comet assay in relationship to the induction of sister chromatid exchanges (SCEs) and micronuclei (MN). Induction of DNA strand breaks was found neither with the standard protocol of the alkaline comet assay nor with modifications using extended electrophoresis times or proteinase K. The concentration-effect relationship for the genotoxic effects was characterized by fitting different curves to the data. A two-phase regression model fitted best in comparison with a linear or a quadratic model and indicated practical thresholds for the induction of SCE and MN. For the induction of DPX as measured by the comet assay, neither a linear concentration-response relationship nor any of the tested models fitted well to the data. Three repeated treatments with genotoxic concentrations of FA with a 3-h interval led to enhanced levels of DPX and MN while the same treatments with a 24-h interval did not enhance FA genotoxicity but suggested adaptive protection against the DNA-damaging action of FA. PMID- 17855735 TI - Epidurally administered mepivacaine delays recovery of train-of-four ratio from vecuronium-induced neuromuscular block. AB - BACKGROUND: The aim of this study was to examine the efficacy of epidurally administered mepivacaine on recovery from vecuronium-induced neuromuscular block. METHODS: Eighty patients were randomly assigned to one of two study groups. They were either given epidurally a bolus of 0.15 ml kg(-1) of mepivacaine 2%, followed by repetitive injections of 0.1 ml kg(-1) h(-1) throughout the study, or were not given epidurally. General anaesthesia was induced and maintained with fentanyl, propofol and nitrous oxide. Neuromuscular block was induced with vecuronium 0.1 mg kg(-1) and monitored using acceleromyographic train-of-four (TOF) at the adductor pollicis. Patients in each treatment group were randomized to receive neostigmine 0.04 mg kg(-1) at 25% recovery of the first twitch of TOF or to recover spontaneously to a TOF ratio of 0.9. The effect of epidural mepivacaine on speed of spontaneous and facilitated recovery of neuromuscular function was evaluated. RESULTS: The time from administration of vecuronium to spontaneous recovery to a TOF ratio of 0.9 was significantly longer in the epidural mepivacaine group [105.4 (14.2) min] as compared with the control group [78.5 (9.1) min, P < 0.01]. Neostigmine administered at 25% of control in T1 shortened recovery from neuromuscular block, however the time required for facilitated recovery to a TOF ratio of 0.9 in the epidural group was significantly longer than that in the control group [7.6 (1.6) min vs 5.8 (2.1) min, P < 0.01]. CONCLUSIONS: In clinical anaesthesia, it should be recognized that epidurally administered mepivacaine delays considerably the TOF recovery from neuromuscular block. PMID- 17855736 TI - Cardiac surgery with cardiopulmonary bypass: does aprotinin affect outcome? AB - BACKGROUND: Aprotinin, a non-specific serine protease inhibitor, has been used for two decades to reduce perioperative blood loss and the risk for allogeneic transfusion in cardiac surgery. This study evaluated the effects of aprotinin on outcome (mortality, cardiac events, renal failure, and cerebrovascular events) in such patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: Data were obtained in patients who received a strict blood conservation protocol: no antifibrinolytic therapy when at low risk (n = 854) and aprotinin (n = 1210) when at high risk for blood transfusion. Relative risk of different pre- and intra-operative variables was calculated for the different outcome variables. Backward stepwise logistic regression analysis was used to identify the independent risk factors associated with the different outcome variables. Statistical significance was accepted at P < 0.01. RESULTS: Postoperative mortality and morbidity were higher in the aprotinin group but this was related to an increased incidence of perioperative risk factors. Mortality was similar to that predicted by the Euroscore. Complex surgery was the only independent variable associated with postoperative cardiac events. Preoperative heart failure, preoperative creatinine > 1.5 mg dl(-1), urgent, and redo surgery were the independent variables associated with postoperative haemodialysis. Age > 70 yr was identified as the only independent variable associated with neurologic dysfunction. CONCLUSIONS: In the present study, patients receiving aprotinin as part of a strict blood conservation strategy represent a population at high risk for postoperative complications. For the outcome variables studied, aprotinin administration was not identified as an independent risk factor. PMID- 17855737 TI - Similarity between the suprasystolic wideband external pulse wave and the first derivative of the intra-arterial pulse wave. AB - BACKGROUND: Wideband external pulse (WEP) monitoring, using a broad bandwidth piezoelectric sensor located over the brachial artery under the distal edge of a sphygmomanometer cuff, can be used for evaluating the contour of the arterial pressure pulse wave. The pulse contour contains valuable information relating to cardiovascular function which may be of clinical use in addition to blood pressure measurements. The aim of this study was to compare the shape of the WEP signal during inflation of the cuff to suprasystolic pressure, with intra arterial pressure waves, after the administration of vasoactive drugs. METHODS: Radial intra-arterial and suprasystolic WEP waveforms were recorded in 11 healthy men (mean 23 yr) before and at the end of infusion of glyceryl trinitrate, angiotensin II, norepinephrine, and salbutamol. Waveform similarity was assessed by comparing the timing and pressure of incident and reflected waves and by root mean square error (RMSE). RESULTS: The WEP signal was found to closely resemble the first derivative of intra-arterial pressure. The WEP signal could be used to derive an arterial pressure wave with minimal bias in the timing of incident [- 8 (18) ms, mean (SD)] and reflected [- 1 (24) ms] waves. Augmentation index was underestimated by WEP [- 7 (18)%]. WEP also provided a measure of compliance which correlated with pulse wave velocity (r = - 0.44). RMSE values after the administration of each of the four drugs mentioned earlier were 12.4 (3.8), 17.7 (5.0), 22.1 (11.7), and 28.9 (22.4) mm Hg, respectively. Changes in derived WEP signals were similar to those measured by arterial line with all drugs. CONCLUSIONS: The suprasystolic WEP signals can be used to derive arterial pressure waves which, although not identical, track changes in the intra-arterial pulse wave induced by vasoactive drugs. PMID- 17855738 TI - Acute chromosomal DNA damage after radiation exposure. PMID- 17855739 TI - Effect of dynamic myocardial dyssynchrony on mitral regurgitation during supine bicycle exercise stress echocardiography in patients with idiopathic dilated cardiomyopathy and 'narrow' QRS. PMID- 17855740 TI - Management of atrial fibrillation in patients with heart failure. AB - Atrial fibrillation (AF) and chronic heart failure (CHF) are two major and even growing cardiovascular conditions that often coexist. However, few data are available to guide treatment of AF in patients with CHF. This review summarizes current literature concerning the following topics: (i) prognostic relevance of AF in patients with CHF, (ii) relevance and strategies of rhythm and rate control in patients with AF and CHF, and (iii) options for prevention of AF in patients with ventricular dysfunction. In conclusion, AF is associated with increased mortality in CHF patients. However, it is not clear whether there is a causal relationship. Emerging strategies to prevent the occurrence of AF are promising tools that might improve quality of life and survival in patients with CHF. PMID- 17855741 TI - A "glyconutrient sham". AB - The discipline of glycobiology contributes to our understanding of human health and disease through research, most of which is published in peer-reviewed scientific journals. Recently, legitimate discoveries in glycobiology have been used as marketing tools to help sell plant extracts termed "glyconutrients." The glyconutrient industry has a worldwide sales force of over half a million people and sells nearly half a billion dollars (USD) of products annually. Here we address the relationship between glyconutrients and glycobiology, and how glyconutrient claims may impact the public and our discipline. PMID- 17855742 TI - Sulfatide binding properties of murine and human antiganglioside antibodies. AB - Antiganglioside antibodies form an important component of the innate and adaptive B cell repertoire, where they provide antimicrobial activity through binding encapsulated bacterial glycans. In an aberrant role, they target peripheral nerve gangliosides to induce autoimmune nerve injury. An important characteristic of antiganglioside antibodies is their ability to selectively recognize highly defined glycan structures. Since sialylated and sulfated glycans often share lectin recognition patterns, we here explored the possibility that certain antiganglioside antibodies might also bind 3-O-sulfo-beta-D-galactosylceramide (sulfatide), an abundant constituent of plasma and peripheral nerve myelin, that could thereby influence any immunoregulatory or autoimmune properties. Out of 25 antiganglioside antibodies screened in solid phase assays, 20 also bound sulfatide (10(-5) to 10(-6) M range) in addition to their favored ganglioside glycan epitope ( approximately 10(-7) M range). Solution inhibition studies demonstrated competition between ganglioside and sulfatide, indicating close proximity or sharing of the antigen binding variable region domain. Sulfatide and 3-O-sulfo-beta-D-galactose were unique in having this property amongst a wide range of sulfated glycans screened, including 4- and 6-O-sulfo-beta-D-galactose analogues. Antiganglioside antibody binding to 3-O-sulfo-beta-D-galactose was highly dependent upon the spatial presentation of the ligand, being completely inhibited by conjugation to protein or polyacrylamide (PAA) matrices. Binding was also absent when sulfatide was incorporated into plasma membranes, including myelin, under conditions in which antibody binding to ganglioside was retained. These data demonstrate that sulfatide binding is a common property of antiganglioside antibodies that may provide functional insights into, and consequences for this component of the innate immune repertoire. PMID- 17855744 TI - Biometrical modelling in genetics: are complex traits too complex? AB - The field of traditional biometrical genetics uses mixed-effects models to quantify the influence of genetic and environmental factors on a biological trait, based essentially on estimating within-family trait correlations. Such analyses provide a useful preview of what may be discovered with the emerging full-scale genotyping strategies. However, biometrical analyses require unrealistically large sample sizes to obtain a reasonable precision, particularly for dichotomous traits. In addition, it may be very difficult to separate genetic and environmental effects because environmental correlations are poorly understood. We illustrate these and other difficulties using population-based cousins and nuclear family data for birth weight, collected from the Medical Birth Registry of Norway. PMID- 17855745 TI - Joint modelling of mixed outcome types using latent variables. AB - After a brief review of the use of latent variables to accommodate the correlation among multiple outcomes of mixed types, through theoretical and numerical calculation, the consequences of such a construction are quantified. The effects of including latent variables on marginal inference in these models are contrasted with the situation for jointly normal outcomes. A simulation study illustrates the efficiency and reduction in bias gains possible in using joint models, and analysis of an example from the field of osteoarthritis illustrates potential practical differences. PMID- 17855746 TI - Latent class and finite mixture models for multilevel data sets. AB - An extension of latent class (LC) and finite mixture models is described for the analysis of hierarchical data sets. As is typical in multilevel analysis, the dependence between lower-level units within higher-level units is dealt with by assuming that certain model parameters differ randomly across higher-level observations. One of the special cases is an LC model in which group-level differences in the logit of belonging to a particular LC are captured with continuous random effects. Other variants are obtained by including random effects in the model for the response variables rather than for the LCs. The variant that receives most attention in this article is an LC model with discrete random effects: higher-level units are clustered based on the likelihood of their members belonging to the various LCs. This yields a model with mixture distributions at two levels, namely at the group and the subject level. This model is illustrated with three rather different empirical examples. The appendix describes an adapted version of the expectation-maximization algorithm that can be used for maximum likelihood estimation, as well as providing setups for estimating the multilevel LC model with generally available software. PMID- 17855747 TI - Bayesian latent variable modelling of multivariate spatio-temporal variation in cancer mortality. AB - In this article, three alternative Bayesian hierarchical latent factor models are described for spatially and temporally correlated multivariate health data. The fundamentals of factor analysis with ideas of space- time disease mapping to provide a flexible framework for the joint analysis of multiple-related diseases in space and time with a view to estimating common and disease-specific trends in cancer risk are combined. The models are applied to area-level mortality data on six diet-related cancers for Greece over the 20-year period from 1980 to 1999. The aim of this study is to uncover the spatial and temporal patterns of any latent factor(s) underlying the cancer data that could be interpreted as reflecting some aspects of the habitual diet of the Greek population. PMID- 17855748 TI - Classical latent variable models for medical research. AB - Latent variable models are commonly used in medical statistics, although often not referred to under this name. In this paper we describe classical latent variable models such as factor analysis, item response theory, latent class models and structural equation models. Their usefulness in medical research is demonstrated using real data. Examples include measurement of forced expiratory flow, measurement of physical disability, diagnosis of myocardial infarction and modelling the determinants of clients' satisfaction with counsellors' interviews. PMID- 17855749 TI - Commentary: methods to increase response rates to postal questionnaires. PMID- 17855750 TI - Corticospinal involvement in volitional contractions. PMID- 17855751 TI - GABA transient sets the susceptibility of mIPSCs to modulation by benzodiazepine receptor agonists in rat hippocampal neurons. AB - Benzodiazepines (BDZs) are known to increase the amplitude and duration of IPSCs. Moreover, at low [GABA], BDZs strongly enhance GABAergic currents suggesting the up-regulation of agonist binding while their action on gating remains a matter of debate. In the present study we have examined the impact of flurazepam and zolpidem on mIPSCs by investigating their effects on GABA(A)R binding and gating and by considering dynamic conditions of synaptic receptor activation. Flurazepam and zolpidem enhanced the amplitude and prolonged decay of mIPSCs. Both compounds strongly enhanced responses to low [GABA] but, surprisingly, decreased the currents evoked by saturating or half-saturating [GABA]. Analysis of current responses to ultrafast GABA applications indicated that these compounds enhanced binding and desensitization of GABA(A) receptors. Flurazepam and zolpidem markedly prolonged deactivation of responses to low [GABA] but had almost no effect on deactivation at saturating or half-saturating [GABA]. Moreover, at low [GABA], flurazepam enhanced desensitization-deactivation coupling but zolpidem did not. Recordings of responses to half-saturating [GABA] applications revealed that appropriate timing of agonist exposure was sufficient to reproduce either a decrease or enhancement of currents by flurazepam or zolpidem. Recordings of currents mediated by recombinant ('synaptic') alpha1beta2gamma2 receptors reproduced all major findings observed for neuronal GABA(A)Rs. We conclude that an extremely brief agonist transient renders IPSCs particularly sensitive to the up-regulation of agonist binding by BDZs. PMID- 17855752 TI - A mutation in the ATP-binding site of the Kir6.2 subunit of the KATP channel alters coupling with the SUR2A subunit. AB - Mutations in the pore-forming subunit of the ATP-sensitive K(+) (K(ATP)) channel Kir6.2 cause neonatal diabetes. Understanding the molecular mechanism of action of these mutations has provided valuable insight into the relationship between the structure and function of the K(ATP) channel. When Kir6.2 containing a mutation (F333I) in the putative ATP-binding site is coexpressed with the cardiac type of regulatory K(ATP) channel subunit, SUR2A, the channel sensitivity to ATP inhibition is reduced and the intrinsic open probability (P(o)) is increased. However, the extent of macroscopic current activation by MgADP was unaffected. Here we examine rundown and MgADP activation of wild-type and Kir6.2-F333I/SUR2A channels using single-channel recording, noise analysis and spectral analysis. We also compare the effect of mutating the adjacent residue, G334, on rundown and MgADP activation. All three approaches indicated that rundown of Kir6.2 F333I/SUR2A channels is due to a reduction in the number of active channels in the patch and that MgADP reactivation involves recruitment of inactive channels. In contrast, rundown and MgADP reactivation of wild-type and Kir6.2-G334D/SUR2A channels, and of Kir6.2-F333I/SUR1 channels, involve a gradual change in P(o). Our results suggest that F333 in Kir6.2 interacts functionally with SUR2A to modulate channel rundown and MgADP activation. This interaction is fairly specific as it is not disturbed when the adjacent residue (G334) is mutated. It is also not a consequence of the enhanced P(o) of Kir6.2-F333I/SUR2A channels, as it is not found for other mutant channels with high P(o) (Kir6.2-I296L/SUR2A). PMID- 17855753 TI - Corticofugal modulation of the auditory thalamic reticular nucleus of the guinea pig. AB - Neuronal responses to auditory stimuli and electrical stimulation were examined in 104 neurones in the auditory sector of thalamic reticular nucleus (TRN) and nine medial geniculate (MGB) neurones from anaesthetized guinea pigs. TRN neurones showed rhythmic spontaneous activities. TRN neurones changed firing pattern over time, from tonic to burst in a time interval of several seconds to tens of seconds. One-third of the TRN neurones (25/76) responded to the acoustic stimulus in a slow oscillation mode, either producing a spike burst at one time and responded with nothing another time, or producing a spike burst at one time and a single spike at the other. Thirty-two of 40 neurones received a corticofugal modulation effect. Nineteen of 32 neurones responded directly to electrical stimulation of the cortex with an oscillation of the same rhythm (7-14 Hz) as its auditory-evoked oscillation. Six neurones changed their firing pattern from burst to tonic when the auditory cortex was activated. As the TRN applied inhibition to the MGB, the oscillatory nature of inhibition would affect the fidelity of MGB relays. Thus, it was unlikely that the MGB was in relay mode when the TRN was in a slow oscillation mode. These results hint at a possible mechanism for the modulation of states of vigilance through the corticofugal pathway via the TRN. PMID- 17855754 TI - The cardiovascular challenge of exercising in the heat. AB - Exercise in the heat can pose a severe challenge to human cardiovascular control, and thus the provision of oxygen to exercising muscles and vital organs, because of enhanced thermoregulatory demand for skin blood flow coupled with dehydration and hyperthermia. Cardiovascular strain, typified by reductions in cardiac output, skin and locomotor muscle blood flow and systemic and muscle oxygen delivery accompanies marked dehydration and hyperthermia during prolonged and intense exercise characteristic of many summer Olympic events. This review focuses on how the cardiovascular system is regulated when exercising in the heat and how restrictions in locomotor skeletal muscle and/or skin perfusion might limit athletic performance in hot environments. PMID- 17855755 TI - Chronic corticosterone elevation and sex-specific augmentation of the hypoxic ventilatory response in awake rats. AB - Perinatal stress disrupts normal development of the hypothalamo-pituitary-adrenal (HPA) axis. Adult male (but not female) rats previously subjected to a stress such as neonatal maternal separation (NMS) are characterized by chronic elevation of plasma corticosterone (Cort) levels and an abnormally elevated hypoxic ventilatory response through mechanisms that remain unknown. The present study tested the hypothesis that a chronic increase of plasma Cort levels alone augments the ventilatory response to hypoxia in adult rats. Three groups of Sprague-Dawley male and female rats were used (control, placebo and Cort implants). Rats subjected to chronic Cort elevation received a subcutaneous Cort implant (300 mg) 14 days prior to ventilatory measurements, whereas sham-operated rats received placebo implants. Controls received no treatment. Plasma Cort levels and body weight profiles were measured to assess protocol efficiency. Whole body plethysmography was used to measure ventilatory activity and metabolic indices during normoxia and following a 20 min period of moderate hypoxia (12% O(2)). Male rats implanted with Cort showed a ventilatory response to hypoxia higher than placebo-treated rats; this effect was mainly due to a larger tidal volume response. In females, Cort treatment increased the breathing frequency response but the effect on minute ventilation was not significant. Taken together, these data show that chronic elevation of Cort alone increases the ventilatory response to hypoxia, but in a sex-specific manner. These data raise important questions regarding the mechanisms underlying the sexual dimorphism of this effect and the potential link between HPA axis dysfunction and respiratory disorders related to abnormal ventilatory chemoreflex. PMID- 17855756 TI - Structural and functional alterations of muscle fibres in the novel mouse model of facioscapulohumeral muscular dystrophy. AB - We recently generated a mouse model of facioscapulohumeral muscular dystrophy (FSHD) by selectively overexpressing FRG1, a candidate gene for FSHD, in skeletal muscle. The muscles of the FRG-1 mice did not show any plasmamembrane defect suggesting a novel pathogenetic mechanism for FSHD. Here, we study structure and function of muscle fibres from three lines of mice overexpressing FRG1 at different levels: FRG1-low, FRG1-med, FRG1-high. Cross-sectional area (CSA), specific force (Po/CSA) and maximum shortening velocity (V(o)) of identified types of muscle fibres from FRG1-low and FRG1-med mice were analysed and found to be lower than in WT mice. Fast fibres and especially type 2B fibres (the fastest type) were preferentially involved in the dystrophic process showing a much larger force deficit than type 1 (slow) fibres. Consistent with the latter observation, the MHC isoform distribution of several muscles of the three FRG1 lines showed a shift towards slower MHC isoforms in comparison to WT muscle. Moreover, fast muscles showed a more evident histological deterioration, a larger atrophy and a higher percentage of centrally nucleated fibres than the soleus, the slowest muscle in mice. Interestingly, loss in CSA, Po/CSA and V(o) of single muscle fibres and MHC isoform shift towards a slower phenotype can be considered early signs of muscular dystrophy (MD). They were, in fact, found also in FRG1 low mice which did not show any impairment of function in vivo and of muscle size in vitro and in soleus muscles, which had a completely preserved morphology. This study provides a detailed characterization of structure and function of muscle fibres in a novel murine model of one of the main human MDs and suggests that fundamental features of the dystrophic process, common to most MDs, such as the intrinsic loss of contractile strength of muscle fibres, the preferential involvement of fast fibres and the shift towards a slow muscle phenotype can occur independently from obvious alterations of the plasma membrane. PMID- 17855757 TI - Disuse of rat muscle in vivo reduces protein kinase C activity controlling the sarcolemma chloride conductance. AB - Muscle disuse produced by hindlimb unloading (HU) induces severe atrophy and slow to-fast fibre type transition of the slow-twitch soleus muscle (Sol). After 2 weeks HU, the resting ClC-1 chloride conductance (g(Cl)) of sarcolemma, which controls muscle excitability, increases in Sol toward a value typical of the fast twitch EDL muscle. After 3 days of HU, the g(Cl) increases as well before initiation of fibre type transition. Since ClC-1 channels are acutely silenced by PKC-dependent phosphorylation, we studied the modulation of g(Cl) by PKC and serine-threonine phosphatase in Sol during HU, using a number of pharmacological tools. We show that a fraction of ClC-1 channels of control Sol are maintained in an inactive state by PKC basal activity, which contributes to the lower g(Cl) in control Sol compared to EDL. After 14 days of HU, PKC/phosphatase manipulation produces effects on Sol g(Cl) that corroborate the partial slow-to-fast transition. After 3 days of HU, the early increase of g(Cl) in Sol is entirely attributable to a reduction of PKC activity and/or activation of phosphatase, maintaining ClC-1 channels in a fully active state. Accordingly, we found that HU reduces expression of PKCalpha, epsilon, and isoenzymes in Sol and EDL muscles and reduces total PKC activity. Moreover, we show that the rheobase current is increased in Sol muscle fibres as soon as after 3 days of HU, most probably in relation to the increased g(Cl). In conclusion, Sol muscle disuse is characterized by a rapid reduction of PKC activity, which reduces muscle excitability and is likely to contribute to disuse-induced muscle impairment. PMID- 17855758 TI - Inspiratory muscle training attenuates the human respiratory muscle metaboreflex. AB - We hypothesized that inspiratory muscle training (IMT) would attenuate the sympathetically mediated heart rate (HR) and mean arterial pressure (MAP) increases normally observed during fatiguing inspiratory muscle work. An experimental group (Exp, n = 8) performed IMT 6 days per week for 5 weeks at 50% of maximal inspiratory pressure (MIP), while a control group (Sham, n = 8) performed IMT at 10% MIP. Pre- and post-training, subjects underwent a eucapnic resistive breathing task (RBT) (breathing frequency = 15 breaths min(-1), duty cycle = 0.70) while HR and MAP were continuously monitored. Following IMT, MIP increased significantly (P < 0.05) in the Exp group (-125 +/- 10 to -146 +/- 12 cmH(2)O; mean +/- s.e.m.) but not in the Sham group (-141 +/- 11 to -148 +/- 11 cmH(2)O). Prior to IMT, the RBT resulted in significant increases in HR (Sham: 59 +/- 2 to 83 +/- 4 beats min(-1); Exp: 62 +/- 3 to 83 +/- 4 beats min(-1)) and MAP (Sham: 88 +/- 2 to 106 +/- 3 mmHg; Exp: 84 +/- 1 to 99 +/- 3 mmHg) in both groups relative to rest. Following IMT, the Sham group observed similar HR and MAP responses to the RBT while the Exp group failed to increase HR and MAP to the same extent as before (HR: 59 +/- 3 to 74 +/- 2 beats min(-1); MAP: 84 +/- 1 to 89 +/- 2 mmHg). This attenuated cardiovascular response suggests a blunted sympatho-excitation to resistive inspiratory work. We attribute our findings to a reduced activity of chemosensitive afferents within the inspiratory muscles and may provide a mechanism for some of the whole-body exercise endurance improvements associated with IMT. PMID- 17855759 TI - Regulation of skeletal muscle PPAR delta mRNA expression in twins. AB - Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors regulating the expression of genes involved in lipid and glucose metabolism in a complex and to some extent unknown manner. Our aim was to study the impact of different factors on PPARdelta mRNA expression in human skeletal muscle on one side, and the impact of PPARdelta mRNA expression on these factors, including glucose and lipid metabolism, aerobic capacity, fibre type composition and lipid profile, on the other side. PPARdelta mRNA levels were quantified by real-time PCR in muscle biopsies from 176 young and elderly monozygotic and dizygotic twins. Young twins had significantly increased PPARdelta mRNA levels compared with elderly twins. A 2 h hyperinsulinaemic euglycaemic clamp had no significant effect on PPARdelta mRNA levels. Biometric models were calculated for basal PPARdelta mRNA expression to estimate the degree of genetic versus environmental influence. In both young and elderly twins there was a substantial genetic component influencing basal PPARdelta mRNA levels. In a regression model, the muscle PPARdelta mRNA expression was correlated to birth weight, central adiposity and age. The level of PPARdelta mRNA was also positively correlated with markers for oxidative muscle fibres. However, in this apparently healthy study population, we found no correlations between PPARdelta mRNA expression and aerobic capacity, lipid profile or glucose and lipid metabolism. In conclusion, we provide evidence that mRNA expression of PPARdelta in human skeletal muscle is under genetic control but also influenced by factors such as age, birth weight and central adiposity. PMID- 17855760 TI - Gating currents from a Kv3 subfamily potassium channel: charge movement and modification by BDS-II toxin. AB - Kv3 channels have a major role in determining neuronal excitability, and are characterized by ultra-rapid kinetics of gating and a high activation threshold. However, the gating currents, which occur as a result of positional changes of the charged elements in the channel structure during activation, are not well understood. Here we report a study of gating currents from wild-type Kv3.2b channels, expressed in human embryonic kidney (HEK) cells to facilitate high time resolution recording. On-gating currents (I(g,on)) had extremely rapid kinetics such that at +80 mV, the time constant for the decay of I(g,on) was only approximately 0.3 ms. Decay of I(g,on) appeared mono-exponential at all potentials studied, and in support of this, the charge-voltage (Q-V) relationship was fitted with a single Boltzmann function, supporting the idea that only one charge system is required to account for the time course of I(g,on) and the voltage dependence of Q(on). The voltage (V((1/2))) for half movement of gating charge was -8.4 +/- 4.0 mV (n = 6), which closely matches the voltage dependence of activation of Kv3.2b ionic currents reported before. Depolarizations to more positive potentials than 0 mV decreased the amplitude and slowed the decay of the off-gating currents (I(g,off)), suggesting that a rate-limiting step in opening was present in Kv3 channels as in Shaker and other Kv channels. Return of charge was negatively shifted along the potential axis with a V((1/2)) of Q(off) of 80.9 +/- 0.8 mV (n = 3), which allowed approximately 90% charge return upon repolarization to -100 mV. BDS-II toxin apparently reduced I(g,on), and greatly slowed the kinetics of I(g,on), while shifting the Q-V relationship in the depolarizing direction. However, the Q-V relationship remained well fitted by a single Boltzmann function. These data provide the first description of Kv3 gating currents and give further insight into the interaction of BDS toxins and Kv3 channels. PMID- 17855761 TI - Human tendon behaviour and adaptation, in vivo. AB - Tendon properties contribute to the complex interaction of the central nervous system, muscle-tendon unit and bony structures to produce joint movement. Until recently limited information on human tendon behaviour in vivo was available; however, novel methodological advancements have enabled new insights to be gained in this area. The present review summarizes the progress made with respect to human tendon and aponeurosis function in vivo, and how tendons adapt to ageing, loading and unloading conditions. During low tensile loading or with passive lengthening not only the muscle is elongated, but also the tendon undergoes significant length changes, which may have implications for reflex responses. During active loading, the length change of the tendon far exceeds that of the aponeurosis, indicating that the aponeurosis may more effectively transfer force onto the tendon, which lengthens and stores elastic energy subsequently released during unloading, in a spring-like manner. In fact, data recently obtained in vivo confirm that, during walking, the human Achilles tendon provides elastic strain energy that can decrease the energy cost of locomotion. Also, new experimental evidence shows that, contrary to earlier beliefs, the metabolic activity in human tendon is remarkably high and this affords the tendon the ability to adapt to changing demands. With ageing and disuse there is a reduction in tendon stiffness, which can be mitigated with resistance exercises. Such adaptations seem advantageous for maintaining movement rapidity, reducing tendon stress and risk of injury, and possibly, for enabling muscles to operate closer to the optimum region of the length-tension relationship. PMID- 17855762 TI - Lipolysis and fatty acid metabolism in men and women during the postexercise recovery period. AB - We sought to determine whether lipolysis, fatty acid (FA) mobilization, and plasma FA oxidation would remain elevated for hours following isoenergetic exercise bouts of different intensities. Ten men and eight women received a primed-continuous infusion of [1,1,2,3,3-(2)H(5)]glycerol and continuous infusion of [1-(13)C]palmitate to measure glycerol and plasma FA kinetics. On Day 1 (D1), participants were studied under one of three different conditions, assigned in random order: (1) before, during and 3 h after 90 min of exercise at 45% V(O2)peak (E45), (2) before, during and 3 h after 60 min of exercise at 65% V(O2)peak (E65), and (3) in a time-matched sedentary control trial (C). For each condition, participants were studied by indirect calorimetry the following morning as well (D2). Rate of appearance (Ra) of glycerol (Ra(GL)) increased above C during exercise in men and women (P < 0.05), was higher in E45 than E65 in men (P < 0.05), and was not different between exercise intensities in women. During 3 h of postexercise recovery, Ra(GL) remained significantly elevated in men (P < 0.05), but not women. FA Ra (Ra(FA)) increased during exercise in men and women and was higher in E45 than E65 (P < 0.05), and remained elevated during 3 h of postexercise recovery in both sexes (P < 0.05), but with a greater relative increase in men than women (P < 0.05). Plasma FA oxidation (Rox) increased during exercise with no difference between intensities, and it remained elevated during 3 h of postexercise recovery in both sexes (P < 0.05). Total lipid oxidation (Lox) was elevated in both sexes (P < 0.05), but more in men during 3 h of postexercise recovery on D1 (P < 0.05) and remained elevated on D2 in men (P < 0.05), but not in women. There were no differences between E45 and E65 for postexercise energy substrate turnover or oxidation in men and women as energy expenditure of exercise (EEE) was matched between bouts. We conclude that the impact of exercise upon lipid metabolism persists into recovery, but that women depend more on lipid during exercise whereas, during recovery, lipid metabolism is accentuated to a greater extent in men. PMID- 17855763 TI - Utilizing intraluminal pressure differences to predict esophageal bolus flow dynamics. AB - Successful esophageal emptying depends on the generation of a sustained intrabolus pressure (IBP) sufficient to overcome esophagogastric junction (EGJ) obstruction. Our aim was to develop a manometric analysis paradigm that describes the bolus driving pressure difference and the flow permissive time for esophageal bolus transit. Twenty normal subjects were studied with a 36-channel manometry assembly (1-cm spacing) during two 5- and one 10-ml barium swallows and concurrent fluoroscopy. Bolus domain pressure plots were generated by plotting bolus domain pressure (BDP) and EGJ relaxation pressure. BDP was defined as the pressure midway between the peristaltic ramp-up and the proximal margin of the EGJ. The flow permissive time was defined as the period where the BDP was > or = EGJ relaxation pressure. The mean BDP was 11.7 +/- 1.0 mmHg (SE), and the mean flow permissive time was 3.9 +/- 0.4 s for 5-ml swallows in normal controls. The mean BDP difference during flow was 4.0 +/- 1.0 mmHg. There was no significant difference in the fluoroscopic transit time and the flow permissive time calculated from the BDP plots (5 ml: fluoroscopy 3.4 +/- 0.2 s; BDP 3.9 +/- 0.4 s, P > 0.05). BDP plots provide a reliable measurement of IBP and its relationship with EGJ relaxation. The time available for flow can be readily delineated from this analysis, and the driving pressure responsible for flow can be accurately described and quantified. This may help predict abnormal bolus transit and the underlying mechanical properties of the EGJ. PMID- 17855764 TI - Expansion of intestinal stem cells associated with long-term adaptation following ileocecal resection in mice. AB - Sustained increases in mucosal surface area occur in remaining bowel following massive intestinal loss. The mechanisms responsible for expanding and perpetuating this response are not presently understood. We hypothesized that an increase in the number of intestinal stem cells (ISC) occurs following intestinal resection and is an important component of the adaptive response in mice. This was assessed in the jejunum of mice 2-3 days, 4-5 days, 6-7 days, 2 wk, 6 wk, and 16 wk following ileocecal resection (ICR) or sham operation. Changes in ISC following ICR compared with sham resulted in increased crypt fission and were assayed by 1) putative ISC population (SP) by flow cytometry, 2) Musashi-1 immunohistochemistry, and 3) bromodeoxyuridine (BrdU) label retention. Observed early increases in crypt depth and villus height were not sustained 16 wk following operation. In contrast, long-term increases in intestinal caliber and overall number of crypts per circumference appear to account for the enhanced mucosal surface area following ICR. Flow cytometry demonstrated that significant increases in SP cells occur within 2-3 days following resection. By 7 days, ICR resulted in marked increases in crypt fission and Musashi-1 immunohistochemistry staining. Separate label-retention studies confirmed a 20-fold increase in BrdU incorporation 6 wk following ICR, confirming an overall increase in the number of ISC. These studies support that expansion of ISC occurs following ICR, leading to an overall increase number of crypts through a process of fission and intestinal dilation. Understanding the mechanism expanding ISCs may provide important insight into management of intestinal failure. PMID- 17855765 TI - Transporters, enzymes, and enalapril removal in a rat (CC531-induced) liver metastatic model. AB - Temporal changes in physiological spaces, protein expression of transporters and enzymes, and enalapril removal were appraised in the metastatic liver tumor model developed from male Wag/Rij rats after the intraportal injection of CC531 colon adenocarcinoma cells; sham-operated preparations received PBS. Liver tissue spaces, investigated with multiple indicator dilution technique in liver perfusion studies, were unchanged at week 3 after tumor induction. At week 4, however, the sinusoidal blood volume and albumin Disse space in tumor-bearing livers were slightly lower compared with those of shams. Increased levels of the canalicular ATP transporters, P-glycoprotein, multidrug resistance-associated protein 2 (Mrp2), and bile salt export pump (Bsep) at week 2 (P < 0.05), unchanged levels of Ntcp, Oatp1a1, Oatp1a4, and Mct2, but decreased levels of cytochrome P450 3a2 (Cyp3a2) and glutathione S-transferase (Gst4-4) at week 4 (P < 0.05) were observed in peritumor vs. sham-operated liver tissues with Western blotting. The steady-state extraction ratio of enalapril, a substrate that enters the liver rapidly via Oatp1a1 and primarily undergoes metabolism by the carboxylesterases, was unaffected by liver metastasis at week 4 regardless of its delivery via the portal vein or hepatic artery into the perfused liver preparations. PMID- 17855766 TI - Transport of butyryl-L-carnitine, a potential prodrug, via the carnitine transporter OCTN2 and the amino acid transporter ATB(0,+). AB - L-carnitine is absorbed in the intestinal tract via the carnitine transporter OCTN2 and the amino acid transporter ATB(0,+). Loss-of-function mutations in OCTN2 may be associated with inflammatory bowel disease (IBD), suggesting a role for carnitine in intestinal/colonic health. In contrast, ATB(0,+) is upregulated in bowel inflammation. Butyrate, a bacterial fermentation product, is beneficial for prevention/treatment of ulcerative colitis. Butyryl-L-carnitine (BC), a butyrate ester of carnitine, may have potential for treatment of gut inflammation, since BC would supply both butyrate and carnitine. We examined the transport of BC via ATB(0,+) to determine if this transporter could serve as a delivery system for BC. We also examined the transport of BC via OCTN2. Studies were done with cloned ATB(0,+) and OCTN2 in heterologous expression systems. BC inhibited ATB(0,+)-mediated glycine transport in mammalian cells (IC(50), 4.6 +/- 0.7 mM). In Xenopus laevis oocytes expressing human ATB(0,+), BC induced Na(+) dependent inward currents under voltage-clamp conditions. The currents were saturable with a K(0.5) of 1.4 +/- 0.1 mM. Na(+) activation kinetics of BC induced currents suggested involvement of two Na(+) per transport cycle. BC also inhibited OCTN2-mediated carnitine uptake (IC(50), 1.5 +/- 0.3 microM). Transport of BC via OCTN2 is electrogenic, as evidenced from BC-induced inward currents. These currents were Na(+) dependent and saturable (K(0.5), 0.40 +/- 0.02 microM). We conclude that ATB(0,+) is a low-affinity/high-capacity transporter for BC, whereas OCTN2 is a high-affinity/low-capacity transporter. ATB(0,+) may mediate intestinal absorption of BC when OCTN2 is defective. PMID- 17855767 TI - Toll-like receptor (TLR) 2 induced through TLR4 signaling initiated by Helicobacter pylori cooperatively amplifies iNOS induction in gastric epithelial cells. AB - Cell-surface Toll-like receptors (TLRs) initiate innate immune responses, such as inducible nitric oxide synthase (iNOS) induction, to microorganisms' surface pathogens. TLR2 and TLR4 play important roles in gastric mucosa infected with Helicobacter pylori (H. pylori), which contains lipopolysaccharide (LPS) as a pathogen. The present study investigates their physiological roles in the innate immune response of gastric epithelial cells to H. pylori-LPS. Changes in the expression of iNOS, TLR2, and TLR4, as well as downstream activation of mitogen activated protein kinases and nuclear factor-kappaB (NF-kappaB), were analyzed in normal mouse gastric mucosal GSM06 cells following stimulation with H. pylori-LPS and interferon-gamma. Specific inhibitors for mitogen-activated protein kinases, NF-kappaB, and small interfering RNA for TLR2 or TLR4 were employed. The immunohistochemistry of TLR2 was examined in human gastric mucosa. H. pylori-LPS stimulation induced TLR2 in GSM06 cells, but TLR4 was unchanged. TLR2 induction resulted from TLR4 signaling that propagated through extracellular signal-related kinase and NF-kappaB activation, as corroborated by the decline in TLR4 expression on small interfering RNA treatment and pretreatment with inhibitors. The induction of iNOS and the associated nitric oxide production in response to H. pylori-LPS stimulation were inhibited by declines in not only TLR4 but also TLR2. Increased expression of TLR2 was identified in H. pylori-infected human gastric mucosa. TLR4 signaling initiated by H. pylori-LPS and propagated via extracellular signal-regulated kinase and NF-kappaB activation induced TLR2 expression in gastric epithelial cells. Induced TLR2 cooperated with TLR4 to amplify iNOS induction. This positive correlation may constitute a mechanism for stimulating the innate immune response against various bacterial pathogens, including H. pylori-LPS. PMID- 17855768 TI - Mapping the dynamics of shear stress-induced structural changes in endothelial cells. AB - Hemodynamic shear stress regulates endothelial cell biochemical processes that govern cytoskeletal contractility, focal adhesion dynamics, and extracellular matrix (ECM) assembly. Since shear stress causes rapid strain focusing at discrete locations in the cytoskeleton, we hypothesized that shear stress coordinately alters structural dynamics in the cytoskeleton, focal adhesion sites, and ECM on a time scale of minutes. Using multiwavelength four-dimensional fluorescence microscopy, we measured the displacement of rhodamine-fibronectin and green fluorescent protein-labeled actin, vimentin, paxillin, and/or vinculin in aortic endothelial cells before and after onset of steady unidirectional shear stress. In the cytoskeleton, the onset of shear stress increased actin polymerization into lamellipodia, altered the angle of lateral displacement of actin stress fibers and vimentin filaments, and decreased centripetal remodeling of actin stress fibers in subconfluent and confluent cell layers. Shear stress induced the formation of new focal complexes and reduced the centripetal remodeling of focal adhesions in regions of new actin polymerization. The structural dynamics of focal adhesions and the fibronectin matrix varied with cell density. In subconfluent cell layers, shear stress onset decreased the displacement of focal adhesions and fibronectin fibrils. In confluent monolayers, the direction of fibronectin and focal adhesion displacement shifted significantly toward the downstream direction within 1 min after onset of shear stress. These spatially coordinated rapid changes in the structural dynamics of cytoskeleton, focal adhesions, and ECM are consistent with focusing of mechanical stress and/or strain near major sites of shear stress-mediated mechanotransduction. PMID- 17855769 TI - Levels of plasma membrane expression in progressive and benign mutations of the bile salt export pump (Bsep/Abcb11) correlate with severity of cholestatic diseases. AB - Human BSEP (ABCB11) mutations are the molecular basis for at least three clinical forms of liver disease, progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2), and intrahepatic cholestasis of pregnancy (ICP). To better understand the pathobiology of these disease phenotypes, we hypothesized that different mutations may cause significant differences in protein defects. Therefore we compared the effect of two PFIC2 mutations (D482G, E297G) with two BRIC2 mutations (A570T and R1050C) and one ICP mutation (N591S) with regard to the subcellular localization, maturation, and function of the rat Bsep protein. Bile salt transport was retained in all but the E297G mutant. Mutant proteins were expressed at reduced levels on the plasma membrane of transfected HEK293 cells compared with wild-type (WT) Bsep in the following order: WT > N591S > R1050C approximately A570T approximately E297G >> D482G. Total cell protein and surface protein expression were reduced to the same extent, suggesting that trafficking of these mutants to the plasma membrane is not impaired. All Bsep mutants accumulate in perinuclear aggresome-like structures in the presence of the proteasome inhibitor MG-132, suggesting that mutations are associated with protein instability and ubiquitin-dependent degradation. Reduced temperature, sodium butyrate, and sodium 4-phenylbutyrate enhanced the expression of the mature and cell surface D482G protein in HEK293 cells. These results suggest that the clinical phenotypes of PFIC2, BRIC2, and ICP may directly correlate with the amount of mature protein that is expressed at the cell surface and that strategies to stabilize cell surface mutant protein may be therapeutic. PMID- 17855770 TI - Tight junction targeting and intracellular trafficking of occludin in polarized epithelial cells. AB - Occludin, a transmembrane (TM)-spanning protein, is an integral component of the tight junctional (TJ) complexes that regulate epithelial integrity and paracellular barrier function. However, the molecular determinants that dictate occludin targeting and delivery to the TJs remain unclear. Here, using live cell imaging of yellow fluorescent protein-labeled occludin fragments, we resolved the intracellular trafficking of occludin-fusion proteins in polarized Madin-Darby canine kidney and Caco-2 cells to delineate the regions within the occludin polypeptide that are important for occludin targeting to the TJs. Live cell confocal imaging showed that complete or partial truncation of the COOH-terminal tail of the occludin polypeptide did not prevent occludin targeting to the TJs in epithelial cell lines. Progressive truncations into the COOH-terminal tail decreased the efficiency of occludin expression; after the removal of the regions proximal to the fourth transmembrane domain (TM4), the efficiency of expression increased. However, further deletions into the TM4 abolished TJ targeting, which resulted in constructs that were retained intracellularly within the endoplasmic reticulum. The full-length occludin polypeptide trafficked to the cell surface within a heterogenous population of intracellular vesicles that delivered occludin to the plasma membrane in a microtubule- and temperature-dependent manner. In contrast, the steady-state localization of occludin at the cell surface was dependent on intact microfilaments but not microtubules. PMID- 17855771 TI - Juxtacrine activation of EGFR regulates claudin expression and increases transepithelial resistance. AB - Heparin-binding (HB)-EGF, a ligand for EGF receptors, is synthesized as a membrane-anchored precursor that is potentially capable of juxtacrine activation of EGF receptors. However, the physiological importance of such juxtacrine signaling remains poorly described, due to frequent inability to distinguish effects mediated by membrane-anchored HB-EGF vs. mature "secreted HB-EGF." In our studies, using stable expression of a noncleavable, membrane-anchored rat HB-EGF isoform (MDCK(rat5aa) cells) in Madin-Darby canine kidney (MDCK) II cells, we observed a significant increase in transepithelial resistance (TER). Similar significant increases in TER were observed on stable expression of an analogous, noncleavable, membrane-anchored human HB-EGF construct (MDCK(human5aa) cells). The presence of noncleavable, membrane-anchored HB-EGF led to alterations in the expression of selected claudin family members, including a marked decrease in claudin-2 in MDCK(rat5aa) cells compared with the control MDCK cells. Reexpression of claudin-2 in MDCK(rat5aa) cells largely prevented the increases in TER. Ion substitution studies indicated decreased paracellular ionic permeability of Na(+) in MDCK(rat5aa) cells, further indicating that the altered claudin-2 expression mediated the increased TER seen in these cells. In a Ca(2+) switch model, increased phosphorylation of EGF receptor and Akt was observed in MDCK(rat5aa) cells compared with the control MDCK cells, and inhibition of these pathways inhibited TER changes specifically in MDCK(rat5aa) cells. Therefore, we hypothesize that juxtacrine activation of EGFR by membrane-anchored HB-EGF may play an important role in the regulation of tight junction proteins and TER. PMID- 17855772 TI - Cystathionine-beta-synthase gene transfer and 3-deazaadenosine ameliorate inflammatory response in endothelial cells. AB - Although elevated levels of homocysteine (Hcy) known as hyperhomocysteinemia (HHcy) are associated with increased inflammation and vascular remodeling, the mechanism of Hcy-mediated inflammation and vascular remodeling is unclear. The matrix metalloproteinases (MMPs) and adhesion molecules play an important role in vascular remodeling. We hypothesized that HHcy induces inflammation by increasing adhesion molecules and matrix protein expression. Endothelial cells were supplemented with high methionine, and Hcy accumulation was measured by HPLC. Nitric oxide (NO) bioavailability was detected by a NO probe. The protein expression was measured by Western blot analysis. MMP-9 activity was detected by gelatin-gel zymography. We demonstrated that methionine supplement promoted upregulation of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) through increased Hcy accumulation. In addition, increased synthesis of collagen type-1 was also observed. MMP-9 gene expression and protein activity were increased in methionine supplement groups. 3 Deazaadenosine (DZA), an adenosine analogue, prevented high methionine-induced ICAM-1 and VCAM-1 expression and collagen type-1 synthesis. Transfection of endothelial cells with cystathionine-beta-synthase (CBS) gene construct, which converts Hcy to cystathionine, reduced Hcy accumulation in high methionine-fed cells. CBS gene transfection reduced the inflammatory response, as evident by attenuated ICAM-1 and VCAM-1 expression. Furthermore, collagen type-1 expression and MMP-9 activity were dramatically attenuated with CBS gene transfection. These results suggested that methionine supplement increased Hcy accumulation, which was associated with inflammatory response and matrix remodeling such as collagen type-1 synthesis and MMP-9 activity. However, in vitro DZA and CBS gene therapy successfully treated the HHcy-induced inflammatory reaction in the methionine metabolism pathway. PMID- 17855773 TI - Voltage-gated Ca2+ currents are necessary for slow-wave propagation in the canine gastric antrum. AB - Electrical slow waves determine the timing and force of peristaltic contractions in the stomach. Slow waves originate from a dominant pacemaker in the orad corpus and propagate actively around and down the stomach to the pylorus. The mechanism of slow-wave propagation is controversial. We tested whether Ca(2+) entry via a voltage-dependent, dihydropyridine-resistant Ca(2+) conductance is necessary for active propagation in canine gastric antral muscles. Muscle strips cut parallel to the circular muscle were studied with intracellular electrophysiological techniques using a partitioned-chamber apparatus. Slow-wave upstroke velocity and plateau amplitude decreased from the greater to the lesser curvature, and this corresponded to a decrease in the density of interstitial cells of Cajal in the lesser curvature. Slow-wave propagation velocity between electrodes impaling cells in two regions of muscle and slow-wave upstroke and plateau were measured in response to experimental conditions that reduce the driving force for Ca(2+) entry or block voltage-dependent Ca(2+) currents. Nicardipine (0.1-1 microM) did not affect slow-wave upstroke or propagation velocities. Upstroke velocity, amplitude, and propagation velocity were reduced in a concentration-dependent manner by Ni(2+) (1-100 microM), mibefradil (10-30 microM), and reduced extracellular Ca(2+) (0.5-1.5 mM). Depolarization (by 10-15 mM K(+)) or hyperpolarization (10 microM pinacidil) also reduced upstroke and propagation velocities. The higher concentrations (or lowest Ca(2+)) of these drugs and ionic conditions tested blocked slow-wave propagation. Treatment with cyclopiazonic acid to empty Ca(2+) stores did not affect propagation. These experiments show that voltage-dependent Ca(2+) entry is obligatory for the upstroke phase of slow waves and active propagation. PMID- 17855774 TI - C/EBPbeta phosphorylation rescues macrophage dysfunction and apoptosis induced by anthrax lethal toxin. AB - Bacillus anthracis lethal toxin (LT) impairs innate and adaptive immunity. Anthrax lethal factor stimulates cleavage of MAPK kinases, which prevents the activation of antiapoptotic MAPK targets. However, these MAPK targets have not been yet identified. Here, we found that LT induces macrophage apoptosis by enhancing caspase 8 activation and by preventing the activation of ribosomal S6 kinase-2 (RSK), a MAPK target, and the phosphorylation of CCAAT/enhancer binding protein-beta (C/EBPbeta) on T(217), a RSK target. Expression of the dominant positive, phosphorylation mimic C/EBPbeta-E(217) rescued macrophages from LT induced apoptosis by blocking the activation of procaspase 8. LT inhibited macrophage phagocytosis and oxidative burst and induced apoptosis in normal mice but not in C/EBPbeta-E(217) transgenic mice. These findings suggest that C/EBPbeta may play a critical role in anthrax pathogenesis, at least in macrophages. PMID- 17855775 TI - Xin, an actin binding protein, is expressed within muscle satellite cells and newly regenerated skeletal muscle fibers. AB - Xin is a muscle-specific actin binding protein of which its role and regulation within skeletal muscle is not well understood. Here we demonstrate that Xin mRNA is robustly upregulated (>16-fold) within 12 h of skeletal muscle injury and is localized to the muscle satellite cell population. RT-PCR confirmed the expression pattern of Xin during regeneration, as well as within primary muscle myoblast cultures, but not other known stem cell populations. Immunohistochemical staining of single myofibers demonstrate Xin expression colocalized with the satellite cell marker Syndecan-4 further supporting the mRNA expression of Xin in satellite cells. In situ hybridization of regenerating muscle 5-7 days postinjury illustrates Xin expression within newly regenerated myofibers. Promoter-reporter assays demonstrate that known myogenic transcription factors [myocyte enhancer factor-2 (MEF2), myogenic differentiation-1 (MyoD), and myogenic factor-5 (Myf 5)] transactivate Xin promoter constructs supporting the muscle-specific expression of Xin. To determine the role of Xin within muscle precursor cells, proliferation, migration, and differentiation analysis using Xin, short hairpin RNA (shRNA) were undertaken in C2C12 myoblasts. Reducing endogenous Xin expression resulted in a 26% increase (P < 0.05) in cell proliferation and a 20% increase (P < 0.05) in myoblast migratory capacity. Skeletal muscle myosin heavy chain protein levels were increased (P < 0.05) with Xin shRNA administration; however, this was not accompanied by changes in myoglobin protein (another marker of differentiation) nor overt morphological differences relative to differentiating control cells. Taken together, the present findings support the hypothesis that Xin is expressed within muscle satellite cells during skeletal muscle regeneration and is involved in the regulation of myoblast function. PMID- 17855776 TI - Changes of gap junctional cell-cell communication in overactive detrusor in rats. AB - To evaluate the changes in intercellular communication through gap junctions in detrusor overactivity (DO), we studied 23 adult female Wistar rats with DO after partial outflow obstruction (DO group) and 13 sham-operated rats (control group). The two groups were compared by means of urodynamics, light and electron microscopy, expression of Cx40, Cx43, and Cx45 mRNA genes with RT-PCR, Cx43 protein with Western blot analysis, and functional intercellular communication with scrape loading dye transfer (SLDT) and fluorescence recovery after photobleaching (FRAP). The number of gap junctions and the expression of connexin mRNA and Cx43 protein were increased in DO rats, and intercellular communication through gap junctions increased after 6 wk of partial outflow obstruction as assessed with SLDT and FRAP techniques. The findings provide a theoretical rationale for using Cx43 antagonists and gap junction inhibitors in the treatment of patients with overactive detrusor secondary to partial bladder outflow obstruction. PMID- 17855777 TI - Radiofrequency ablation of an epicardial ventricular tachycardia through the great cardiac vein in a patient with mitro-aortic mechanical prostheses. AB - AIMS: Prior cardiac surgery limits epicardial ventricular tachycardia (VT) ablation due to epicardial adhesions formation. METHODS AND RESULTS: We describe an epicardial VT ablation through the coronary venous system in a patient with mechanical mitro-aortic prostheses. The different possible ablation approaches and their potential limitations are discussed. CONCLUSION: In selected patients, especially after cardiac surgery, coronary venous system approach can be considered as a safety possible approach for the ablation of some epicardial VTs. PMID- 17855778 TI - Transhepatic approach for a small paracaval tumor in repeat resection. AB - To resect a small liver tumor located in the paracaval portion, we adopted transhepatic enucleation, i.e. enucleation of the tumor from the transected plane along the main portal fissure. In contrast to caudate lobectomy, this procedure can save dissection around the liver and vena cava, which would increase operation time and blood loss especially in repeat surgery after removal of Couinaud's segment VII or the right lateral sector. It can also minimize the liver parenchymal volume to be resected. The transhepatic enucleation would be a safe and recommendable surgical technique for a small paracaval tumor in repeat resection and/or in patients with poor liver functional reserve. PMID- 17855779 TI - Where does the first lateral pelvic lymph node receive drainage from? AB - BACKGROUND: Lateral pelvic lymph node dissection (LPLD) in the treatment of rectal cancer has risks and benefits. Avoidance of unnecessary LPLD is important, however, preoperative and/or intraoperative accurate detection of lateral lymph node metastases have not been established. If the lateral lymph node to which the fluid first spread from the primary lower rectal cancer is detected accurately, it may guide the need for LPLD and may assist in avoiding unnecessary dissection. METHODS: A total of 14 patients with T3 lower rectal cancer were evaluated to locate the lymph nodes through which indocyanine green (ICG) reached the lymphatics. After ICG was injected into the lower rectum via an endoscope preoperatively, total mesorectal excision was first performed, and LPLD was performed with infrared ray electronic endoscopy (IREE) to assess the degree of retention of ICG in each regional lymph node. RESULTS: Drainage of ICG to lateral pelvic lymph nodes was observed in 6 of 14 patients (43%). All ICG-containing lymph nodes were detected by IREE. When present, lateral pelvic wall lymph node drainage was limited exclusively to the peri-internal iliac artery nodes. No obturator nodes were involved. CONCLUSION: The first lateral lymph node that receives lymphatic drainage from lower rectal cancer is located around the internal iliac arteries. PMID- 17855780 TI - Chyle leakage and early enteral feeding following pancreatico-duodenectomy: management options. AB - BACKGROUND: Chyle leaks are a rare complication following abdominal surgery. The aim of this study is to describe the management of chyle leaks following surgery for pancreatico-duodenal malignancy. METHODS: Data were collated from a consecutive series of 105 patients who had undergone a pancreatico-duodenectomy for malignancy. From this cohort, patients who developed significant chyle leaks, defined as drainage of more than 600 ml of amylase-poor chylous fluid per day, were identified and their management reviewed. RESULTS: A total of 7 (6.7%) patients with significant chyle leaks were identified. All but one of the chyle leaks were identified between the 5th and 9th post-operative day. Early restoration of enteral feeding appeared to increase the incidence of chyle leak. Six of the 7 patients were successfully treated conservatively with total parenteral nutrition and after a median of 7.5 days the chyle leak had resolved. One patient required a peritoneovenous shunt for chylous ascites. CONCLUSION: This study has described a high incidence of chyle leak among patients undergoing surgery for pancreatico-duodenal malignancy. Early introduction of enteral feed may encourage development. However, patients who develop an abdominal chyle leak remain clinically well and the leak can be managed relatively easily with parenteral nutrition. PMID- 17855781 TI - European survey on the application of vascular clamping in liver surgery. AB - BACKGROUND: This study evaluated the frequency, the indications and techniques of vascular clamping during liver resection and during thermal destruction therapies, as currently used by hepatic surgeons throughout Europe. METHODS: A web-based questionnaire was distributed among 621 physicians, including all members of the European Hepato-Pancreato-Biliary Association and the European Surgical Association. RESULTS: The overall response rate was 50%. During liver resection, vascular clamping is never applied by 10%, on indication by 71%, and routinely by 19%. Routine clamping is particularly performed by high-volume and senior surgeons and appears to be associated with longer ischaemia times. Intermittent inflow occlusion is the clamping method of choice for more than 65% of surgeons and total ischaemia times are usually limited to 15-30 min. During thermal ablation, vascular clamping is never used by 57%, on indication by 37%, and routinely by 7%; it is particularly applied for large tumours and for tumours close to large vessels, and ischaemia times are shorter. CONCLUSIONS: Vascular clamping during liver resection is frequently used; during thermal ablation it is preserved for larger tumours or tumours in the vicinity of large vessels. Complete inflow occlusion is the most frequently used technique, with a distinct preference for intermittent clamping. PMID- 17855782 TI - Treatment of grade 2 and 3 hemorrhoids with Doppler-guided hemorrhoidal artery ligation. AB - AIM: We evaluated the results of the Doppler-guided hemorrhoidal arterial ligation (DG-HAL) method in the management of symptomatic grade 2 and 3 hemorrhoids. PATIENTS AND METHODS: Between June 2005 and March 2006, 110 consecutive patients with symptomatic grade 2 and 3 hemorrhoids according to the DG-HAL method were treated. All procedures were performed in daycare under spinal anesthesia. The primary objective was the reduction in hemorrhoidal gradation as determined by proctoscopy; the secondary was patient satisfaction. This was measured by interviewing patients over the telephone. RESULTS: The average age was 47.6 years. 42 patients had grade 2 hemorrhoids, 68 grade 3. An average of 7.3 ligations were placed. Proctoscopy showed that, after 6 weeks, 97 (88%) patients had a significant improvement in their hemorrhoidal gradation. After an average follow-up of 37 weeks, 93 of the 110 (84.5%) patients were satisfied with the postoperative result. Mortality was 0% and morbidity 3%. CONCLUSION: DG-HAL is a safe and effective treatment in the management of symptomatic grade 2 and 3 hemorrhoids. PMID- 17855783 TI - Primate origins: implications of a cretaceous ancestry. AB - It has long been accepted that the adaptive radiation of modern placental mammals, like that of modern birds, did not begin until after the Cretaceous/Tertiary (K/T) boundary 65 million years (Ma) ago, following the extinction of the dinosaurs. The first undoubted fossil relatives of modern primates appear in the record 55 Ma ago. However, in agreement with evidence from molecular phylogenies calibrated with dates from denser parts of the fossil record, a statistical analysis of the primate record allowing for major gaps now indicates a Cretaceous origin of euprimates 80-90 Ma ago. If this interpretation is correct, primates overlapped with dinosaurs by some 20 Ma prior to the K/T boundary, and the initial radiation of primates was probably truncated as part of the major extinction event that occurred at the end of the Cretaceous. Following a review of evidence for an early origin of primates, implications of this are discussed with respect to the likely ancestral condition for primates, including a southern continental area of origin and moderately large body size. The known early Tertiary primates are re-interpreted as northern continental offshoots of a 'second wave' of primate evolution. PMID- 17855784 TI - Invading Europe: did climate or geography trigger early Eocene primate dispersals? AB - The Palaeocene-Eocene transition is characterized by a significant turnover of mammalian taxa in the fossil record of the northern continents, and primates are among the groups that make their first appearance at this time. One of the many questions that remain to be answered with regard to the earliest evolution of primates is the reason for their sudden and virtually simultaneous appearance in the fossil records of Asia, Europe and North America. The most obvious environmental correlate of the Palaeocene-Eocene transition is a sharp but relatively short-lived warming event leading up to the Palaeocene-Eocene thermal maximum (PETM) and evidenced in the stratigraphic record by a negative delta(13)C excursion. It remains unclear, however, whether or how this warming event may have influenced Palaeocene-Eocene faunal turnovers. This paper explores the hypothesis that environmental changes associated with the PETM facilitated an invasion of Western Europe by primates by comparing the ecological structure of local mammalian fauna immediately before and following the Palaeocene-Eocene transition. The results suggest that changes to the ecological profile of local mammalian fauna were relatively small and did not favour an invasion by primates, although a major uncertainty remains with respect to the availability of arboreal niches. At present it seems more likely that the invasion of western Europe by primates was due to the breakdown of one or more dispersal barriers close to the end of the Palaeocene. PMID- 17855785 TI - Evolution and extinction of Afro-Arabian primates near the Eocene-Oligocene boundary. AB - Revised age estimates for the primate-bearing localities of the Jebel Qatrani Formation (Fayum area, northern Egypt) have provided a new perspective on primate response to early Oligocene climate change in North Africa. Environmental changes associated with early Oligocene cooling might have driven the local extinction of at least 4 strepsirrhine primate clades (adapids, djebelemurines, plesiopithecids and galagids). Contrary to previous suggestions, oligopithecid (and possibly proteopithecid) anthropoids persisted beyond the Eocene-Oligocene boundary (EOB) in the Fayum area, and the former group evidently continued to diversify through the early Oligocene at lower latitudes. Propliopithecids and parapithecine parapithecids first appear in the Jebel Qatrani Formation millions of years after the EOB, so their derived dental and gnathic features can no longer be interpreted as sudden adaptive morphological responses to earliest Oligocene climatic events. Evidence for latitudinal contraction of Afro-Arabian primate distribution through the early Oligocene suggests that the profound late Oligocene restructuring of Afro-Arabian primate communities is most likely to have occurred in equatorial and low-latitude tropical Africa. PMID- 17855786 TI - Middle Miocene dispersals of apes. AB - The earliest record of fossil apes outside Africa is in the latest early Miocene of Turkey and eastern Europe. There were at least 2, and perhaps 4, species of ape, which were found associated with subtropical mixed environments of forest and more open woodland. Postcranial morphology is similar to that of early Miocene primates and indicates mainly generalized arboreal quadrupedal behaviours similar to those of less specialized New World monkeys such as Cebus. Robust jaws and thick enamelled teeth indicate a hard fruit diet. The 2 best known species of fossil ape are known from the site of Pasalar in Turkey. They have almost identical molar and jaw morphology. Molar morphology is also similar to that of specimens from Germany and Slovakia, but there are significant differences in the anterior teeth of the 2 Pasalar species. The more common species, Griphopithecus alpani, shares mainly primitive characters with early and middle Miocene apes in Africa, and it is most similar phenetically to Equatorius africanus from Maboko Island and Kipsaramon. The second species is assigned to a new species of Kenyapithecus, an African genus from Fort Ternan in Kenya, on the basis of a number of shared derived characters of the anterior dentition, and it is considered likely that there is a phylogenetic link between them. The African sites all date from the middle Miocene, similar in age to the Turkish and European ones, and the earliest emigration of apes from Africa coincides with the closure of the Tethys Sea preceding the Langhian transgression. Environments indicated for the African sites are mixtures of seasonal woodlands with some forest vegetation. The postcrania of both African taxa again indicate generalized arboreal adaptation but lacking specialized arboreal function. This middle Miocene radiation of both African and non-African apes was preceded by a radiation of arboreal catarrhine primates in the early Miocene, among which were the earliest apes. The earliest Miocene apes in the genus Proconsul and Rangwapithecus were arboreal, and because of their association with the fruits of evergreen rain forest plants at Mfwangano Island, it would appear that they were forest adapted, i.e. were living in multi-storied evergreen forest. The same or similar species of the same genera from Rusinga Island, together with other genera such as Nyanzapithecus and the small ape Limnopithecus, were associated with plants and animals indicating seasonal woodland environments, probably with gallery forest forming corridors alongside rivers. While the stem ancestors of the Hominoidea were almost certainly forest adapted, the evidence of environments associated with apes in the later part of the early Miocene and the middle Miocene of East Africa indicates more seasonal woodlands, similar to those reconstructed for the middle Miocene of Pasalar in Turkey. This environmental shift was probably a requisite for the successful emigration of apes out of Africa and made possible later movement between the continents for much of the middle Miocene, including possible re-entry of at least one ape lineage back into Africa. PMID- 17855787 TI - Environmental correlates of the cercopithecoid radiations. AB - Modern Old World monkeys live in an array of habitats, an ability that was established early in their evolutionary history. The Old World monkey radiation is commonly correlated with the general trend of climatic cooling in the Neogene and the associated increase in open habitats. However, although they became more abundant and speciated extensively in the very late Miocene, Pliocene and Pleistocene, many of the major events in cercopithecoid evolution occurred before the onset of the late Miocene long cooling period. In the Plio-Pleistocene, regional environmental change and interspecific competition probably influenced the radiations of the Old World monkeys in Africa much more than did global climatic patterns. In southern Africa, the evolution of the monkey community is tied to Pleistocene increases in grassland and open habitats. In East Africa, the more diverse cercopithecid fauna reflects the presence of a wider variety of habitats, including forest, woodland and grassland. PMID- 17855788 TI - Climatic influences on the evolution of early Homo? AB - The nature of the human fossil record is less than ideal for the generation of precise correlations between environmental variables and patterns of evolution in specific lineages. Nonetheless, a critical look at what can and cannot be said from individual fossil morphology and the correlation of specific environmental proxies with specific hominin fossils may lead to a greater understanding of the degree of certainty with which we should embrace environmental hypotheses for the evolution of Homo. Climate shifts have been implicated in both the origin of the genus and its dispersal from Africa. Here, I consider three areas in which a climatic influence has been posited to explain evolutionary shifts in the genus Homo: the origin and dispersal of the genus from Africa; geography, climate and body size in early Homo, and the influence of climate-induced sea level rise on morphological isolation in H. erectus. Each of the data sets is far from ideal, and interpretations of each of the data sets are fraught with issues of equifinality. Of the three hypotheses discussed, the clearest link is seen between latitudinal variation (and presumably temperature) and body size in H. erectus. Similarly, climate-induced sea level change seems a reasonable isolating mechanism to explain the pattern of cranial variation in later Asian H. erectus, but the distribution could also reflect incompletely sampled clinal variation. Alternatively, only equivocal support is found for the influence of climate on the differentiation of H. erectus from H. habilis (as proxied by body/brain size scaling), and therefore the dispersal of the genus Homo cannot be as clearly linked to changes in body size and shape as it has been in the past. These preliminary data suggest that an emphasis on understanding local adaptation before looking at global (and specific) level change is critical to elucidating the importance of climatic factors on the evolution of the genus Homo. PMID- 17855789 TI - Primate visual signals in noisy environments. AB - Most animals and plants need to send signals and rely on some sort of response. For an active receptor of signals, virtually all the signal transmissions that litter the environment, bar those that are functional at any given moment, can be described as 'noise'. I concentrate here on some primate examples where loud calls combine with 'loud' colouring and patterns, to suggest that increasing the intensity of signals can help overcome the problem of 'noise'. I also present evidence that certain ecological conditions favour use of the visual channel. I use some examples, drawn from African guenons, to suggest that visual patterns broadcast on this channel have evolved and have, effectively, been elaborated to conform with certain optical principles. These optical properties minimize ambiguity and enhance species-specific (or at least population-specific) distinctiveness. The abilities of ancestral forest primates to discriminate between functional signals and visual 'noise' may have played an important part in providing the basis for our own hominin ancestors' visual proficiencies. PMID- 17855790 TI - The evolution of extinction risk: past and present anthropogenic impacts on the primate communities of Madagascar. AB - There are two possible approaches to understanding natural and human-induced changes in the primate communities of Madagascar. One is to begin with present day and recent historic interactions and work backwards. A second is to begin with paleoecological records of Malagasy primate communities before and immediately following human arrival, and the associated evidence of human and nonhuman primate interactions, and work forwards. On the basis of biological and climatic studies, as well as historic and ethnohistoric records, we are beginning to understand the abiotic and biotic characteristics of Madagascar's habitats, the lemurs' ecological adaptations to these unique habitats, the extent of forest loss, fragmentation and hunting, and the differential vulnerability of extant lemur species to these pressures. On the basis of integrated paleoecological, archaeological and paleontological research, we have begun to construct a detailed chronology for late prehistoric Madagascar. We are beginning to understand the complex sequence of events that led to one of the most dramatic recent megafaunal extinction/extirpation events. Combining the perspectives of the past and the present, we see a complex set of interactions affecting an initially rich but vulnerable fauna. The total evidence refutes any simple, unicausal (e.g. hunting/habitat destruction/climate change) explanation of megafaunal extinctions, yet unequivocally supports a major role--both direct and indirect--for humans as the trigger of the extinction process. It also supports a change over time in the relative importance of hunting versus habitat loss, and in the trophic characteristics of the primate communities in Madagascar. PMID- 17855791 TI - Biodiversity, phylogeography, biogeography and conservation: lemurs as an example. AB - The lemurs of Madagascar represent a spectacular example of adaptive radiation among primates. Given the special setting under which they evolved (i.e. long isolation, geographical location, geological relief), they provide excellent models for study in many realms, and at different levels and scales, including diversity. At the same time, they occur in a 'hottest hot spot' region for biodiversity conservation. Although there is no single definition of biodiversity, the most commonly used units to measure biodiversity are species species richness, species abundance and, for conservation purposes in particular, species endemism. However, what a species actually is or how, precisely, it should be defined are unresolved issues. Many species concepts have been proposed and several have been used in primatology in recent years. Nowadays, one of the more common approaches to measuring diversity, and eventually inferring species status, is to look at genetic diversity as reflected by mitochondrial DNA differences. Not enough attention has been paid, however, to the different levels at which genetic differences may occur. Lemurs provide instructive examples to highlight the questions involved in species recognition and definition. Using lemurs as examples, I will highlight the strengths and limitations of some analytical tools, including phylogeography and cladistic biogeography and, I will, in particular, emphasize the questions arising at the interface of scientific and conservation perceptions, both of which influence decisions in the field of biodiversity preservation. PMID- 17855792 TI - Distribution of diurnal primate species in Togo and Benin. AB - The Dahomey Gap, a strip of forest-savanna mosaic that interrupts the lowland rainforests of West Africa, is supposed to have acted as a natural barrier to the distribution of forest-dwelling mammals. However, few thorough mammal surveys have been conducted in this region. This study intended to gather distributional data and help clarify the distribution limits of diurnal primates occurring within this 'Gap'. Southern Togo and Benin were surveyed between June and November 2003. The surveys consisted of interviews with hunters and guards from parks and reserves, and walking surveys of forests. As a result, seven diurnal primate species are listed for Togo and Benin. PMID- 17855793 TI - The disregarded West: diet and behavioural ecology of olive baboons in the Ivory Coast. AB - Despite living under environmental conditions considerably distinct from those of savannah baboons (Papio spp.) in East and southern Africa, very little is known about western Papio populations. We monitored the abundance and group sizes of olive baboons (P. anubis) in the savannah-forest mosaic of the Comoe National Park, northern Ivory Coast, and observed 2 habituated groups of different sizes. Against expectations for the kind of habitat, the individual density was low, yielding only 1.2 baboons/km(2). The groups were small, comprising on average 15 individuals, and the proportion of 1-male groups (50-63%) was remarkably high. One-male groups were more female biased than multi-male groups. The baboons were highly frugivorous, spending about 50% of their feeding time on fruits and seeds of at least 79 woody plant species. The 2 habituated groups had comparatively large home ranges and used forests more often than expected by random. We argue that regular subgrouping of the larger focal group and different habitat quality countervailed inter-group variations. Differences from other study sites, however, are not completely explained by current models of baboon (socio)ecology. It appears that the social organization of olive baboons is more flexible than assumed from data on East African populations. PMID- 17855794 TI - Impact of smoking during pregnancy on peripheral tissue oxygenation in term neonates. AB - BACKGROUND: Smoking during pregnancy is associated with higher blood pressure in neonates. OBJECTIVE: To analyze whether smoking during pregnancy has an influence on peripheral tissue oxygenation in healthy term neonates within the first days after delivery. METHODS: In a prospective cohort study, 15 healthy term neonates of mothers who had smoked during pregnancy (smoking group) were matched for gestational age, actual weight and postnatal age to 15 healthy term neonates of mothers who had not smoked during pregnancy (non-smoking group). Peripheral oxygenation was measured by near-infrared spectroscopy in combination with the venous occlusion method on the left forearm. Measurements were performed within the first 2 days after delivery. Tissue oxygenation index (TOI), fractional oxygen extraction (FOE), oxygen delivery (DO(2)) and oxygen consumption (VO(2)) were analyzed. RESULTS: In neonates measured within the first day after delivery, TOI was significantly lower and FOE was significantly higher (63.5 +/- 5.5; 0.37 +/- 0.04) in the smoking group compared to the non-smoking group (69.2 +/- 2.9; 0.30 +/- 0.04). DO(2) tended to be lower and VO(2) tended to be higher in the smoking group. In neonates measured on the second day after delivery, no significant differences were observed between the groups. CONCLUSIONS: Smoking during pregnancy reduced TOI and increased FOE in otherwise healthy neonates on the first day of life with normalization on the second day of life. PMID- 17855795 TI - Feasibility of sequential therapy with FOLFIRI followed by docetaxel/cisplatin in patients with radically resected gastric adenocarcinoma. A randomized phase III trial. AB - OBJECTIVE: Combination therapies of fluorouracil (FU) with irinotecan (CPT-11) and docetaxel plus cisplatin have been proven to be active in metastatic gastric cancer. In this paper, we present the results of a phase III trial in which these two combinations given sequentially were compared to mitomycin C (MMC) monochemotherapy in an adjuvant setting. METHODS: 169 patients with radically resected gastric cancer were randomized to receive CPT-11 (180 mg/m2 day 1), leucovorin (100 mg/m2 days 1-2), FU (400-600 mg/m2 days 1-2, q 14; for four cycles; FOLFIRI regimen), followed by docetaxel (85 mg/m2 day 1), cisplatin (75 mg/m2 day 1, q 21; for three cycles; arm A), or MMC (8 mg/m2 days 1-2 as 2-hour infusion, q 42; for four cycles; arm B). All patients had histologically confirmed gastric carcinoma with nodal positivity or pT3/4. A total of 166 patients (85 in arm A and 81 in arm B) were treated. Adjuvant treatment was completed in 76% of the patients in arm A and in 70% of the patients in arm B. The main grade 3/4 side effects recorded were neutropenia in 35%, with only 1 febrile patient, and diarrhea in 11% in arm A, and thrombocytopenia in 10% and neutropenia in 7% in arm B. The FOLFIRI regimen and docetaxel/cisplatin given in sequence was well tolerated and feasible in adjuvant setting. This sequence treatment currently represents the experimental arm of an ongoing multicenter trial. PMID- 17855796 TI - PNAS-2: a novel gene probably participating in leukemogenesis. AB - OBJECTIVE: As(4)S(4) is an effective drug for the treatment of acute promyelocytic leukemia but its mechanism of action remains largely unknown. In a previous study, we identified PNAS-2, a human apoptosis-related protein gene, using gene expression profiling. In this study, we tried to clarify the role of PNAS-2 in apoptosis and leukemogenesis. METHODS: NB4 and U937 leukemia cell lines and serial clinical samples were studied. RNA interference (RNAi) and RNA overexpression were used to address the potential role of PNAS-2 in apoptosis. PNAS-2 expression was examined using Northern blot in multiple tissues, and real time PCR was applied to analyze PNAS-2 expression in various patient samples. RESULTS: Functional analyses of PNAS-2 by RNAi and RNA overexpression indicate PNAS-2 is an anti-apoptosis gene. PNAS-2 expression is significantly increased in de novo or relapsed acute leukemia, but in patients in complete remission PNAS-2 levels decrease to levels comparable to those found in normal controls. In carcinomas, PNAS-2 expression was not upregulated, indicating that PNAS-2 overexpression was specific for leukemia. CONCLUSION: Based on the preliminary data, we suggest that the PNAS-2 gene functions as an anti-apoptotic gene and probably participates in leukemogenesis. PMID- 17855797 TI - Sentinel lymph nodes in melanoma patients: evaluating the evidence. PMID- 17855798 TI - Estimating the proportion of young adults on antihypertensive treatment that have been correctly diagnosed. AB - This paper aims to identify how many young adults on antihypertensive treatment have been misclassified as hypertensive. We identified subjects aged under 35 on antihypertensive treatment, from the Health Surveys for England, 1998-2004. Pretreatment systolic and diastolic blood pressures were calculated by adjusting on-treatment blood pressures for the effects of treatment. Treatment effects were derived from meta-analysis. Subjects were classified as hypertensive if pretreatment blood pressure was >or=160/100 mm Hg, or was >or=140/90 mm Hg in conjunction with high cardiovascular risk. We then identified the proportion of treated subjects on antihypertensive treatment who were truly eligible for treatment. From the survey data we identified 65 adults (25 men and 40 women) under 35 on diuretics, beta-blockers, angiotensin converting enzyme inhibitors, calcium blockers or other antihypertensives. Average pretreatment blood pressure was 164/100 mm Hg in those eligible for treatment, and 136/79 mm Hg in those not eligible. The analysis indicated that 29.2% of adults aged 16-34 (95% confidence interval (CI): 18.6-41.8%) were truly eligible for antihypertensive treatment: 32.0% (95% CI: 14.9-53.5%) of men and 25.0% (95% CI: 12.7-41.2%) of women. A total of 73.7% (14 of 19) of subjects eligible and 41.3% (19 of 46) of subjects not eligible for treatment either had a body mass index >30 kg m(-2) or kidney disease (chi(2)-test P=0.018). Because of biological variation in blood pressure, most young adults on treatment for hypertension have been misclassified as hypertensive. Most who have been correctly diagnosed are either clinically obese or have kidney disease. PMID- 17855799 TI - Association between the serum anion gap and blood pressure among patients at Harvard Vanguard Medical Associates. AB - Animal and human data suggest a link between endogenous acid production with elevations in blood pressure and the development of hypertension; increases in endogenous organic acid production can lead to a higher anion gap. We studied the cross-sectional association between the serum anion gap and blood pressure among 1057 non-diabetic patients who were not taking antihypertensive drugs, and who received their care at a multisite, multispecialty group practice in eastern Massachusetts. Using linear regression controlling for age, sex, race, BMI, estimated GFR and presence of impaired fasting glucose, every 1 mEq l(-1) higher serum anion gap was associated with a 0.27 mm Hg (P=0.08) higher systolic, 0.20 mm Hg (P=0.05) higher diastolic and 0.22 mm Hg (P=0.04) higher mean arterial pressure; these results suggest that endogenous acid production may raise the risk of hypertension. PMID- 17855800 TI - Characteristics of the patients referred to a Hypertension Unit between 1989 and 2003. AB - The level of blood pressure, the type of antihypertensive treatment and the prevalence of resistant hypertension at the first examination were evaluated in 6254 patients referred to a hospital Hypertension Unit from 1989 to 2003. From 1989-1993 to 1999-2003, we observed a reduced prevalence of grade 2 and grade 3 hypertension, and an increase in the prevalence of grade 1 hypertension, the proportion of treated subjects, the average number of antihypertensive drugs per patient and the prevalence of resistant hypertension. PMID- 17855801 TI - Managing cardiovascular risk: the need for change. PMID- 17855802 TI - Sex specifically associated promoter polymorphism in multiple sclerosis affects interleukin 4 expression levels. AB - The interleukin 4 promoter polymorphism -589 C/T (rs2243250) was genotyped in 869 multiple sclerosis (MS) patients and 595 healthy blood donors. Sex-specific MS association was evident whereas two flanking polymorphisms showed insignificant P values. In dual luciferase assays of cultured Jurkat cells the cloned promoter comprising the -589 T allele leads to higher expression as compared to the respective construct with the C allele. Together these findings may be discussed functionally as contributing to the genetic predisposition and to the pathogenesis in MS. PMID- 17855803 TI - Polymorphisms in Toll-like receptors-2 and -4 are not associated with disease manifestations in acute Q fever. AB - Coxiella burnetii is a macrophage-tropic, Gram-negative organism, which causes acute Q fever infection in humans. This zoonotic infection causes illness ranging from asymptomatic seroconversion to severe and protracted disease featuring hepatitis and pneumonia. Interactions between C. burnetii lipopolysaccharide (LPS) and host Toll-like receptors (TLR)-2 and -4 have been implicated in pathogen recognition, phagocytosis and signaling responses. Nonconservative single nucleotide polymorphisms in the coding regions of TLR-2 (Arg677Trp and Arg753Gln) and TLR-4 (Asp299Gly) have been found to correlate with mycobacterial infections and Gram-negative sepsis respectively. Associations between the TLR-2 and -4 polymorphisms, illness characteristics and immune response parameters were examined in subjects with acute Q fever (n=85) and comparison subjects with viral infections (n=162). No correlation was demonstrated between these polymorphisms and susceptibility to Q fever, illness severity or illness course. PMID- 17855804 TI - Do platelet transfusions in the NICU adversely affect survival? Analysis of 1600 thrombocytopenic neonates in a multihospital healthcare system. AB - OBJECTIVE: Several studies have indicated a correlation between the number of platelet transfusions received by newborn intensive care unit (NICU) patients and the mortality rate. The number of platelet transfusions might be a marker for level of illness, and thus predictive of mortality. However, an alternative hypothesis is that multiple platelet transfusions themselves are harmful in this population. STUDY DESIGN: We evaluated data from all thrombocytopenic neonates cared for in the Intermountain Healthcare NICUs in the past 4 years, seeking associations between the lowest platelet count recorded, number of platelet transfusions received and mortality rate. We also conducted a sensitivity analysis to examine the hypothesis that platelet transfusions were responsible for some fraction of the mortality rate. RESULT: Transfusion and outcome data were examined from 1600 thrombocytopenic NICU patients. At any level of platelet count, some patients received platelet transfusions but others did not. However, at all levels of platelet count, those that received platelet transfusions had a higher mortality rate. Neonates not given any platelet transfusions had a mortality rate of 2%, those with 1 or 2 transfusions had a mortality rate of 11% (P<0.001); those with >10 had a mortality rate of 35% (P<0.001); and those with > or = 20 had a mortality rate of 50% (P<0.001). A sensitivity analysis suggested that the platelet transfusions themselves were very likely responsible for some fraction of the increasing mortality rate. CONCLUSION: The number of platelet transfusions administered in the NICU predicts the mortality rate. Some of this correlation is ascribable to unknown and unmeasured factors such as level of illness. However, the present data and the sensitivity analysis both suggest that some of this correlation is due to harmful effects of multiple platelet transfusions in this group of patients. PMID- 17855805 TI - Heated humidified high-flow nasal cannula: use and a neonatal early extubation protocol. AB - OBJECTIVE: Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) are frequent complications of prematurity. To decrease ventilator-induced lung injury, we evaluated the safety, efficacy and neonatal outcomes of a heated humidified high-flow nasal cannula (HFNC) system and an early extubation protocol (EEP) designed for preterm infants 25 to 29 weeks' gestational age (GA). STUDY DESIGN: The Vapotherm (VT) high-flow humidification system was introduced to our unit in March 2004. After 10 months of VT use, an EEP was developed to begin January 2005. Infants 25 to 29 weeks of GA, intubated for RDS, were enrolled in January-December 2005 to extubate to VT following the EEP. Exclusion criteria were: major congenital anomalies, asphyxia and a 5 min Apgar score <5. Variables examined included BPD, growth and infection. Subjects were compared to historical controls, admitted January to December 2003, prior to the use of VT. RESULT: Inclusion criteria were met by 49/57 infants in the control group and 65/75 infants in the HFNC group. The groups had similar demographics, perinatal conditions, birthweight, GA, timing and total doses of surfactant. There were no differences in rates of extubation failure, patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, laser eye surgery, sepsis, BPD at 28 days and 36 weeks and death. The groups did not differ in oxygen use, i.v. steroid days, or parenteral nutrition days. Days to reach full feeds were similar. Infants in the HFNC group were extubated from a higher ventilator rate (32.6+/-8.5 vs 28+/-7.5, P=0.003) and spent fewer days on the ventilator (11.4+/-12.8 vs 18.5+/-21, P=0.028). Rates of ventilator-associated pneumonia were higher in the control group (P=0.018). Discharge weights were greater in the HFNC group (P=0.016) despite similar length of stay and GA at discharge. CONCLUSION: High-flow nasal cannula use appears safe and well-tolerated. Infants extubated to HFNC spent fewer days on the ventilator. Additional benefits may include a decreased rate of ventilator associated with pneumonia and improved growth. PMID- 17855806 TI - Procedural pain guidelines for the newborn in the United Kingdom. AB - OBJECTIVE: To assess the use of analgesia guidelines for newborn infants in the United Kingdom. STUDY DESIGN: Postal questionnaire to every neonatal unit in the United Kingdom. RESULT: A total of 192 of 244 units replied (78.7% response). Most units had a guideline for elective intubation (70%), sedation for ventilation (78%) post-operative pain (when appropriate) (74%). Less prevalent were guidelines for painful minor procedures (35%). Only 33% of units gave a sweet-tasting solution for analgesia before routine painful procedures and 12% used a topical anesthetic cream. CONCLUSION: Since the last survey in 2000 there has been a modest increased uptake in measures to prevent pain neonatal pain in the United Kingdom, but no pain guideline was present in almost 25% of units and no guideline for routine painful procedures in the majority. PMID- 17855807 TI - Maternal and fetal variation in genes of cholesterol metabolism is associated with preterm delivery. AB - OBJECTIVE: To examine the contribution of variants in fetal and maternal cholesterol metabolism genes in preterm delivery (PTD). STUDY DESIGN: A total of 40 single-nucleotide polymorphisms (SNPs) in 16 genes related to cholesterol metabolism were examined for 414 preterm infants (gestational ages 22 to 36 weeks; comprising 305 singletons and 109 twins) and at least 1 parent. Fetal effects were assessed using the transmission disequilibrium test (TDT) for each SNP, followed by a log linear model-based approach to utilize families with missing parental genotypes for those SNPs showing significance under TDT. Genetic variant effects were examined for a role in PTD, gestational age and birth weight. Maternal effects were estimated using a log linear model-based approach. RESULT: Among singleton gestations, suggestive association (P<0.01 without adjusting for multiple comparisons) was found between birth weight and fetal DHCR7 gene/SNP combinations (rs1630498, P=0.002 and rs2002064, P=0.003). Among all gestations, suggestive associations were found between PTD and fetal HMGCR (rs2303152, P=0.002) and APOA1 (rs 5070, P=0.004). The result for HMGCR was further supported by the log linear model-based test in the single births (P=0.007) and in all births (P=0.006). New associations (APOE and ABCA1) were observed when birth weight was normalized for gestational age suggesting independent effects of variants on birth weight separate from effects on PTD. Testing for maternally mediated genetic effects has identified suggestive association between ABCA1 (rs4149313, P=0.004) and decreased gestational age. CONCLUSION: Variants in maternal and fetal genes for cholesterol metabolism were associated with PTD and decreased birth weight or gestational age in this study. Genetic markers may serve as one mechanism to identify high-risk mothers and fetuses for targeted nutritional treatment and/or prevention of low birth weight or PTD. PMID- 17855808 TI - The Bologna process. PMID- 17855809 TI - A telemedicine cardiac network. Interview by Mark Nicholls. PMID- 17855810 TI - Editorial comment: nephron-sparing surgery has become a standard surgical option for low-stage renal tumours. PMID- 17855811 TI - Interspecific interactions in phytophagous insects revisited: a quantitative assessment of competition theory. AB - The importance of interspecific competition is a highly controversial and unresolved issue for community ecology in general, and for phytophagous insects in particular. Recent advancements, however, in our understanding of indirect (plant- and enemy-mediated) interactions challenge the historical paradigms of competition. Thus, in the context of this rapidly developing field, we re evaluate the evidence for interspecific competition in phytophagous insects using a meta-analysis of published studies. Our analysis is specifically designed to test the assumptions underlying traditional competition theory, namely that competitive interactions are symmetrical, necessitate spatial and temporal co occurrence, and increase in intensity as the density, phylogenetic similarity, and niche overlap of competing species increase. Despite finding frequent evidence for competition, we found very little evidence that plant-feeding insects conform to theoretical predictions for interspecific competition. Interactions were highly asymmetrical, similar in magnitude within vs. between feeding guilds (chewers vs. sap-feeders), and were unaffected by the quantity of resources removed (% defoliation). There was mixed support for the effects of phylogeny, spatial/temporal separation, and the relative strength of intra- vs. interspecific competition. Clearly, a new paradigm that accounts for indirect interactions and facilitation is required to describe how interspecific competition contributes to the organization of phytophagous insect communities, and perhaps to other plant and animal communities as well. PMID- 17855812 TI - Author! Author! By Caveman. PMID- 17855813 TI - Signal transduction mechanisms of CD137 ligand in human monocytes. AB - Bidirectional signalling, i.e. simultaneous signalling through a receptor as well as its cell surface-bound ligand has been identified for several members of the TNF and TNF receptor family members. Reverse signalling through the ligands offers the advantage of an immediate feed-back and a more precise fine tuning of biological responses. Little is known about the molecular nature of reverse signalling through the ligands. CD137 ligand, member of the TNF family is expressed on monocytes and induces activation, migration, prolongation of survival and proliferation of monocytes. Here we show that reverse signalling by CD137 ligand is mediated by protein tyrosine kinases, p38 mitogen activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1,2, MAP/ERK kinase (MEK), Phosphoinositide-3-kinase (PI3-K) and protein kinase A (PKA) but not by protein kinase C (PKC). This study also shows that reverse signalling relies on the same signal transduction molecules as signalling through classical receptors and is in its nature not different from it. PMID- 17855814 TI - Respiratory weakness is associated with limb weakness and delayed weaning in critical illness. AB - OBJECTIVE: Although critical illness neuromyopathy might interfere with weaning from mechanical ventilation, its respiratory component has not been investigated. We designed a study to assess the level of respiratory muscle weakness emerging during the intensive care unit stay in mechanically ventilated patients and to examine the correlation between respiratory and limb muscle strength and the specific contribution of respiratory weakness to delayed weaning. DESIGN: Prospective observational study. SETTING: Two medical, one surgical, and one medicosurgical intensive care units in two university hospitals and one university- affiliated hospital. PATIENTS: A total of 116 consecutive patients were enrolled after >or=7 days of mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Maximal inspiratory and expiratory pressures and vital capacity were measured via the tracheal tube on the first day of return to normal consciousness. Muscle strength was measured using the Medical Research Council score. After standardized weaning, successful extubation was defined as the day from which mechanical ventilatory support was no longer required within the next 15 days. The median value (interquartile range) of maximal inspiratory pressure was 30 (20-40) cm H2O, maximal expiratory pressure was 30 (20-50) cm H2O, and vital capacity was 11.1 (6.3-19.8) mL/kg. Maximal inspiratory pressure, maximal expiratory pressure, and vital capacity were significantly correlated with the Medical Research Council score. The median time (interquartile range) from awakening to successful extubation was 6 (1-17) days. Low maximal inspiratory pressure (hazard ratio, 1.86; 95% confidence interval, 1.07-3.23), maximal expiratory pressure (hazard ratio, 2.18; 95% confidence interval, 1.44 3.84), and Medical Research Council score (hazard ratio, 1.96; 95% confidence interval, 1.27-3.02) were independent predictors of delayed extubation. Septic shock before awakening was significantly associated with respiratory weakness (odds ratio, 3.17; 95% confidence interval, 1.17-8.58). CONCLUSIONS: Respiratory and limb muscle strength are both altered after 1 wk of mechanical ventilation. Respiratory muscle weakness is associated with delayed extubation and prolonged ventilation. In our study, septic shock is a contributor to respiratory weakness. PMID- 17855815 TI - The influence of early hemodynamic optimization on biomarker patterns of severe sepsis and septic shock. AB - BACKGROUND: Despite abundant experimental studies of biomarker patterns in early severe sepsis and septic shock, human data are few. Further, the impact of the severity of global tissue hypoxia resulting from resuscitative strategies on these early biomarker patterns remains unknown. METHODS: The temporal patterns of interleukin-1 receptor antagonist, intercellular adhesion molecule-1, tumor necrosis factor-alpha, caspase-3, and interleukin-8 were serially examined over the first 72 hrs of hospitalization after early hemodynamic optimization strategies of early goal-directed vs. standard therapy for severe sepsis and septic shock patients. The relationship of these biomarker patterns to each hemodynamic optimization strategy, severity of global tissue hypoxia (reflected by lactate and central venous oxygen saturation), organ dysfunction, and mortality were examined. RESULTS: Abnormal biomarker levels were present upon hospital presentation and modulated to distinct patterns within 3 hrs based on the hemodynamic optimization strategy. The temporal expression of these patterns over 72 hrs was significantly associated with the severity of global tissue hypoxia, organ dysfunction, and mortality. CONCLUSION: In early severe sepsis and septic shock, within the first 3 hrs of hospital presentation, distinct biomarker patterns emerge in response to hemodynamic optimization strategies. A significant association exists between temporal biomarker patterns in the first 72 hrs, severity of global tissue hypoxia, organ dysfunction, and mortality. These findings identify global tissue hypoxia as an important contributor to the early inflammatory response and support the role of hemodynamic optimization in supplementing other established therapies during this diagnostic and therapeutic "window of opportunity." PMID- 17855816 TI - Survival and long-term functional outcome in 1,155 consecutive neurocritical care patients. AB - OBJECTIVE: To analyze survival, mortality, and long-term functional disability outcome and to determine predictors of unfavorable outcome in critically ill patients admitted to a neurologic intensive care unit (neuro-ICU). DESIGN: Retrospective cohort study with post-neuro-ICU health-related evaluation of functional long-term outcome. SETTING: Ten-bed neuro-ICU in a tertiary care university hospital. PATIENTS: A consecutive cohort of 1,155 patients admitted to a neuro-ICU during a 36-month period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 1,155 consecutive patients, of whom 41% were women, were enrolled in the study. The predominant reasons for neuro-ICU care were cerebrovascular diseases, such as intracerebral hemorrhage (20%), subarachnoid hemorrhage (16%), and complicated, malignant ischemic stroke (15%). A total of 213 patients (18%) died in the neuro-ICU. The Glasgow Outcome Scale and modified Rankin scale were dichotomized into two groups determining unfavorable vs. favorable outcome (Glasgow Outcome Scale scores 1-3 vs. 4-5 and modified Rankin scale scores 2-6 vs. 0-1). Factors associated with unfavorable outcome in the unselected cohort according to logistic regression analysis were admission diagnosis, age (p < .01), and a higher score in the simplified Therapeutic Intervention Scoring System (TISS-28) at time of admission (p < .01). Functional long-term outcome was evaluated by telephone interview for 662 patients after a median follow-up of approximately 2.5 yrs by evaluating modified Rankin scale and Glasgow Outcome Scale scores. Factors associated with unfavorable functional long term outcome were admission diagnosis, sex, age of >70 yrs (odds ratio, 8.45; 95% confidence interval, 4.52-15.83; p < .01), TISS-28 of >40 points at admission (odds ratio, 4.05; 95% confidence interval, 2.54-6.44; p < .01), TISS-28 of >40 points at discharge from the neuro-ICU (odds ratio, 3.50; 95% confidence interval, 1.51-8.09; p < .01), and length of stay (odds ratio, 1.01; 95% confidence interval, 1.00-1.03; p = .02). CONCLUSION: We found admission diagnosis, age, length of stay, and TISS-28 scores at admission and discharge to be independent predictors of unfavorable long-term outcome in an unselected neurocritical care population. PMID- 17855817 TI - Effect of a nurse-implemented sedation protocol on the incidence of ventilator associated pneumonia. AB - OBJECTIVE: To determine whether the use of a nurse-implemented sedation protocol could reduce the incidence of ventilator-associated pneumonia in critically ill patients. DESIGN: Two-phase (before-after), prospective, controlled study. SETTING: University-affiliated, 11-bed medical intensive care unit. PATIENTS: Patients requiring mechanical ventilation for >or=48 hrs and sedative infusion with midazolam or propofol alone. INTERVENTIONS: During the control phase, sedatives were adjusted according to the physician's decision. During the protocol phase, sedatives were adjusted according to a protocol developed by a multidisciplinary team including nurses and physicians. The protocol was based on the Cambridge scale, and sedation level was adjusted every 3 hrs by the nurses. Standard practices, including weaning from the ventilator and diagnosis of VAP, were the same during both study phases. MEASUREMENTS AND MAIN RESULTS: A total of 423 patients were enrolled (control group, n = 226; protocol group, n = 197). The incidence of VAP was significantly lower in the protocol group compared with the control group (6% and 15%, respectively, p = .005). By univariate analysis (log rank test), only use of a nurse-implemented protocol was significantly associated with a decrease of incidence of VAP (p < .01). A nurse-implemented protocol was found to be independently associated with a lower incidence of VAP after adjustment on Simplified Acute Physiology Score II in the multivariate Cox proportional hazards model (hazard rate, 0.81; 95% confidence interval, 0.62 0.95; p = .03). The median duration of mechanical ventilation was significantly shorter in the protocol group (4.2 days; interquartile range, 2.1-9.5) compared with the control group (8 days; interquartile range, 2.2-22.0; p = .001), representing a 52% relative reduction. Extubation failure was more frequently observed in the control group compared with the protocol group (13% and 6%, respectively, p = .01). There was no significant difference in in-hospital mortality (38% vs. 45% in the protocol vs. control group, respectively, p = .22). CONCLUSIONS: In patients receiving mechanical ventilation and requiring sedative infusions with midazolam or propofol, the use of a nurse-implemented sedation protocol decreases the rate of VAP and the duration of mechanical ventilation. PMID- 17855818 TI - Management strategies for patients with pulmonary hypertension in the intensive care unit. AB - OBJECTIVE: Pulmonary hypertension may be encountered in the intensive care unit in patients with critical illnesses such as acute respiratory distress syndrome, left ventricular dysfunction, and pulmonary embolism, as well as after cardiothoracic surgery. Pulmonary hypertension also may be encountered in patients with preexisting pulmonary vascular, lung, liver, or cardiac diseases. The intensive care unit management of patients can prove extremely challenging, particularly when they become hemodynamically unstable. The objective of this review is to discuss the pathogenesis and physiology of pulmonary hypertension and the utility of various diagnostic tools, and to provide recommendations regarding the use of vasopressors and pulmonary vasodilators in intensive care. DATA SOURCES AND EXTRACTION: We undertook a comprehensive review of the literature regarding the management of pulmonary hypertension in the setting of critical illness. We performed a MEDLINE search of articles published from January 1970 to March 2007. Medical subject headings and keywords searched and cross-referenced with each other were: pulmonary hypertension, vasopressor agents, therapeutics, critical illness, intensive care, right ventricular failure, mitral stenosis, prostacyclin, nitric oxide, sildenafil, dopamine, dobutamine, phenylephrine, isoproterenol, and vasopressin. Both human and animal studies related to pulmonary hypertension were reviewed. CONCLUSIONS: Pulmonary hypertension presents a particular challenge in critically ill patients, because typical therapies such as volume resuscitation and mechanical ventilation may worsen hemodynamics in patients with pulmonary hypertension and right ventricular failure. Patients with decompensated pulmonary hypertension, including those with pulmonary hypertension associated with cardiothoracic surgery, require therapy for right ventricular failure. Very few human studies have addressed the use of vasopressors and pulmonary vasodilators in these patients, but the use of dobutamine, milrinone, inhaled nitric oxide, and intravenous prostacyclin have the greatest support in the literature. Treatment of pulmonary hypertension resulting from critical illness or chronic lung diseases should address the primary cause of hemodynamic deterioration, and pulmonary vasodilators usually are not necessary. PMID- 17855819 TI - Workflow in intensive care unit remote monitoring: A time-and-motion study. AB - OBJECTIVE: To investigate workflow in intensive care unit remote monitoring, a technology-driven practice that allows critical care specialists to perform proactive and continuous patient care from a remote site. DESIGN: A time-and motion study. SETTING: Facility that remotely monitored 132 beds in nine intensive care units. PARTICIPANTS: Six physicians and seven registered nurses. INTERVENTIONS: Participants were observed for 47 and 39 hrs, respectively. MEASUREMENTS AND MAIN RESULTS: Clinicians' workflow was analyzed as goal-oriented tasks and activities. Major variables of interest included the times spent on different types of tasks and activities, the frequencies of accessing various information resources, and the occurrence and management of interruptions in workflow. Physicians spent 70%, 3%, 3%, and 24% of their time on patient monitoring, collaboration, system maintenance, and administrative/social/personal tasks, respectively. For nurses, the time allocations were 46%, 3%, 4%, and 17%, respectively. Nurses spent another 30% of their time maintaining health records. In monitoring patients, physicians spent more percentage times communicating with others than the nurses (13% vs. 7%, p = .026) and accessed the in-unit clinical information system more frequently (42 vs. 14 times per hour, p = .027), while nurses spent more percentage times monitoring real-time vitals (16% vs. 2%, p = .012). Physicians' and nurses' workflows were interrupted at a rate of 2.2 and 7.5 times per hour (p < .001), with an average duration of 101 and 45 secs, respectively (p = .006). The sources of interruptions were significantly different for physicians and nurses (p < .001). CONCLUSIONS: Physicians' and nurses' task performance and information utilization reflect the distributed nature of work organization in intensive care unit remote monitoring. Workflow interruption, clinical information system usability, and collaboration with bedside caregivers are the major issues that may affect the quality and efficiency of clinicians' work in this particular critical care setting. PMID- 17855820 TI - Assessment of hyperglycemia after calcium channel blocker overdoses involving diltiazem or verapamil. AB - BACKGROUND: Overdoses of calcium channel blocker agents result in hyperglycemia, primarily due to the blockade of pancreatic L-type calcium channels and insulin resistance on the cellular level. The clinical significance of the hyperglycemia in this setting has not previously been described. METHODS: This study is a retrospective review of all adult (age, >or=15 yrs) patients with a discharge diagnosis of acute verapamil or diltiazem overdose at five university-affiliated teaching hospitals. The severity of overdose was assessed by determining whether a patient met the composite end points of in-hospital mortality, the necessity for a temporary pacemaker, or the need for vasopressors. We compared the initial and peak serum glucose concentrations with hemodynamic variables between patients who did and did not meet the composite end points. RESULTS: A total of 40 patients met inclusion criteria, with verapamil and diltiazem accounting for 27 of 40 (67.5%) and 13 of 40 (32.5%) of the ingestions, respectively. For those patients who did and did not meet the composite end points, the median initial serum glucose concentrations were 188 (interquartile range, 143.5-270.5) mg/dL and 129 (98.5-156.5) mg/dL, respectively (p = .0058). The median peak serum glucose concentrations for these two groups were 364 (267.5-408.5) mg/dL and 145 (107.5-160.5) mg/dL, respectively (p = .0001). The median increase in blood glucose was 71.2% for those who met composite end points vs. 0% for those who did not meet composite end points (p = .0067). Neither the change in the median heart rate nor the change in systolic blood pressure was significantly different in any group. CONCLUSION: Serum glucose concentrations correlate directly with the severity of the calcium channel blocker intoxication. The percentage increase of the peak glucose concentration is a better predictor of severity of illness than hemodynamic derangements. If validated prospectively, serum glucose concentration alone might be an indicator to begin hyperinsulinemia-euglycemia therapy. PMID- 17855821 TI - The effect of a rapid response team on major clinical outcome measures in a community hospital. AB - OBJECTIVE: To determine the effect of a rapid response system composed primarily of a rapid response team led by physician assistants on the rates of in-hospital cardiac arrests, total and unplanned intensive care unit admissions, and hospital mortality. DESIGN: Prospective, controlled, before and after trial. SETTING: A 350-bed nonteaching community hospital. PATIENTS: All adult patients admitted to the hospital from May 1, 2005, to October 1, 2006. INTERVENTIONS: We introduced a hospital-wide rapid response system that included a rapid response team (RRT) led by physician assistants with specialized critical care training. MEASUREMENTS AND MAIN RESULTS: We measured the incidence of cardiac arrests that occurred outside of the intensive care unit, total intensive care unit admissions, unplanned intensive care unit admissions, intensive care unit length of stay, and the total hospital mortality rate occurring over the study period. There were 344 RRT calls during the study period. In the 5 months before the rapid response system began, there were an average of 7.6 cardiac arrests per 1,000 discharges per month. In the subsequent 13 months, that figure decreased to 3.0 cardiac arrests per 1,000 discharges per month. Overall hospital mortality the year before the rapid response system was 2.82% and decreased to 2.35% by the end of the RRT year. The percentage of intensive care unit admissions that were unplanned decreased from 45% to 29%. Linear regression analysis of key outcome variables showed strong associations with the implementation of the rapid response system, as did analysis of variables over time. Physician assistants successfully managed emergency airway situations without assistance in the majority of cases. CONCLUSIONS: The deployment of an RRT led by physician assistants with specialized skills was associated with significant decreases in rates of in hospital cardiac arrest and unplanned intensive care unit admissions. PMID- 17855822 TI - Facilitating clinician adherence to guidelines in the intensive care unit: A multicenter, qualitative study. AB - OBJECTIVE: To determine perceived facilitators and barriers to guideline implementation and clinician adherence to guidelines in the intensive care unit (ICU). DESIGN: Multicenter qualitative study in three university-affiliated ICUs in Canada. METHODS: We conducted individual semistructured interviews of 44 ICU clinicians (12 intensivists, two physician directors, 12 nurses, three nurse educators, three nurse managers, nine respiratory therapists, and three respiratory therapist educators). We elicited attitudes and perceptions regarding the facilitators and barriers to adherence to guidelines in the ICU. We transcribed all interviews and analyzed data in duplicate using grounded theory to identify themes and develop a model to describe clinicians' views. MAIN RESULTS: The presence of a culture within the ICU that enabled guideline implementation and clinician adherence to guidelines was considered essential. Central to this culture was an ICU team that believed guidelines would reduce practice variation, help implement research findings at the bedside, and result in a more rapid implementation of best practice. Effective leadership and positive interprofessional team dynamics were deemed requisites for this culture. Important strategies identified by the participants to overcome potential barriers to clinician adherence to guidelines were: the presence of effective leaders to promote adoption of the guideline and its adherence, education tailored to the learning preferences of different professional groups, and repeated educational interventions, reminders, and audit and feedback. Participants suggested that the use of strategies to select and prioritize guidelines, simple guideline formats, and electronic media to implement guidelines may further contribute to successful guideline programs. CONCLUSIONS: Complex ICU practices and unique interprofessional team dynamics influence clinician adherence to guidelines. Initiatives that employ an approach addressing these issues may optimize guideline uptake and adherence. The optimal approach and its effectiveness may be guideline-dependent and requires further study. PMID- 17855823 TI - Implementation of early goal-directed therapy for severe sepsis and septic shock: A decision analysis. AB - OBJECTIVE: Early goal-directed therapy (EGDT) reduced mortality from septic shock in a single-center trial. However, implementation of EGDT faces several barriers, including perceived costs and logistic difficulties. We conducted a decision analysis to explore the potential costs and consequences of EGDT implementation. DESIGN: Estimates of effectiveness and resource use were based on data from the original trial and published sources. Implementation costs and lifetime projections were modeled from published sources and tested in sensitivity analyses. We generated incremental cost-effectiveness ratios from the hospital (short-term) and U.S. societal (lifetime) perspectives, excluding nonhealthcare costs, and applying a 3% annual discount. SETTING: Simulation of an average U.S. emergency department. PATIENTS: Total of 1,000 simulation cohorts (n = 263 for each cohort) of adult patients with severe sepsis/septic shock. INTERVENTIONS: EGDT under three alternative implementation strategies: emergency department based, mobile intensive care unit team, and intensive care unit-based (after emergency department transfer). MEASUREMENTS AND MAIN RESULTS: For an average emergency department, we estimated 91 cases per yr, start-up costs from $12,973 (intensive care unit-based) to $26,952 (emergency department-based), and annual outlay of $100,113. EGDT reduced length of stay such that net hospital costs fell approximately 22.9% ($8,413-$8,978). EGDT implementation had a 99.4% to 99.8% probability of being dominant (saved lives and costs) from the hospital perspective, and cost from $2,749 (intensive care unit-based) to $7019 (emergency department-based) per quality-adjusted life-yr with 96.7% to 97.7% probability of being <$20,000 per quality-adjusted life-yr from the societal perspective. The intensive care unit-based strategy was the least expensive, because of lower start-up costs, but also least effective, because of implementation delay, and all three strategies had similar cost-effectiveness ratios. Sensitivity analyses showed these estimates to be particularly sensitive to EGDT's effect on mortality and intensive care unit length of stay, but insensitive to other variables. CONCLUSIONS: EGDT has important start-up costs, and modest delivery costs, but assuming LOS and mortality are reduced, EGDT can be cost-saving to the hospital and associated with favorable lifetime cost-effectiveness projections. PMID- 17855824 TI - Proinflammatory cytokines cause down-regulation of renal chloride entry pathways during sepsis. AB - OBJECTIVE: Sepsis is the most important trigger for acute renal failure, with tubular dysfunction and collapse in urine concentration. As chloride plays a major role in the urinary concentrating mechanisms, we aimed to investigate the regulation of renal chloride entry pathways, such as kidney-specific chloride channel 1, kidney-specific chloride channel 2, Barttin, thiazide-sensitive Na+-Cl cotransporter, renal outer medullary potassium channel, and Na+/K+-adenosine triphosphatase during sepsis. DESIGN: Prospective animal trial. SETTING: Laboratory of the Department of Anesthesiology. SUBJECTS: Male C57/BL6 and B6129SF2/J mice and mice deficient for tumor necrosis factor-alpha, interleukin-1 receptor-1, interferon-gamma, or interleukin-6. INTERVENTIONS: Mice were injected with lipopolysaccharide (LPS) or proinflammatory cytokines. Hemodynamic and renal variables, cytokine concentrations, and expression of renal chloride-reabsorbing systems were investigated. Experiments with cytokine knockout mice, renal artery clipped mice, and mice treated with glucocorticoids, low-dose LPS, and sodium nitroprusside were performed. MEASUREMENTS AND MAIN RESULTS: LPS-injected mice presented with decreased blood pressure and glomerular filtration rate, increased fractional chloride excretion, and depressed expression of renal chloride transporters/channels. Similar alterations were observed after application of tumor necrosis factor-alpha, interleukin-1beta, interferon-gamma, or interleukin 6. LPS-induced down-regulation of chloride transporters/channels was not affected in cytokine knockout mice. Glucocorticoid treatment inhibited LPS-induced increase of cytokine concentrations, diminished LPS-induced renal dysfunction, and attenuated the down-regulation of renal chloride transporters/channels. Injection of low-dose LPS increased renal tissue cytokines and down-regulated chloride entry pathways without arterial hypotension, indicating that renal ischemia due to systemic hypotension does not mediate down-regulation of renal chloride transporters/channels. In addition, renal ischemia induced by renal artery clipping or sodium nitroprusside administration did not influence chloride transporter/channel expression. CONCLUSIONS: Our results demonstrate down regulation of renal chloride transporters/channels during sepsis, which is probably mediated by proinflammatory cytokines and accounts for the development of LPS-induced tubular dysfunction. Our findings contribute to the understanding, on one hand, the failure of single-anticytokine strategies and, on the other hand, the beneficial effects of glucocorticoids in the therapy of septic patients. PMID- 17855825 TI - Mitochondrial resuscitation with exogenous cytochrome c in the septic heart. AB - OBJECTIVE: Mitochondrial dysfunction may play a role in the pathogenesis of sepsis-induced organ dysfunction. Respiratory-chain deficiencies that occur in sepsis, however, have never been shown to cause organ failure or to be reversible. Cytochrome oxidase uses electrons donated by its substrate, cytochrome c, to reduce oxygen to H2O. In the septic heart, cytochrome oxidase is competitively inhibited. We hypothesized that cytochrome oxidase inhibition coupled with reduced substrate availability is a reversible cause of sepsis associated myocardial depression. DESIGN: Prospective observational study aimed to overcome myocardial cytochrome oxidase inhibition with excess cytochrome c and improve cardiac function. SETTING: University hospital-based laboratory. SUBJECTS: Seventy-five C57Bl6 male mice. INTERVENTIONS: Mice underwent cecal ligation and double puncture, sham operation, or no operation. Exogenous cytochrome c or an equal volume of saline was intravenously injected at the 24-hr time point. All animals were evaluated 30 mins after injection. MEASUREMENTS AND MAIN RESULTS: Exogenous cytochrome c readily repleted cardiac mitochondria with supranormal levels of substrate (>1.6 times baseline), restored heme c content, and increased cytochrome oxidase kinetic activity. This increased left ventricular pressure and increased pressure development during isovolumic contraction (dP/dtmax) and relaxation (dP/dtmin) by >45% compared with saline injection. CONCLUSION: Impaired oxidative phosphorylation is a cause of sepsis associated myocardial depression, and mitochondrial resuscitation with exogenous cytochrome c overcomes cytochrome oxidase inhibition and improves cardiac function. PMID- 17855826 TI - Enhanced heat shock protein 70 expression alters proteasomal degradation of IkappaB kinase in experimental acute respiratory distress syndrome. AB - OBJECTIVES: Acute respiratory distress syndrome is a common and highly lethal inflammatory lung syndrome. We previously have shown that an adenoviral vector expressing the heat shock protein (Hsp)70 (AdHSP) protects against experimental sepsis-induced acute respiratory distress syndrome in part by limiting neutrophil accumulation in the lung. Neutrophil accumulation and activation is modulated, in part, by the nuclear factor-kappaB (NF-kappaB) signal transduction pathway. NF kappaB activation requires dissociation/degradation of a bound inhibitor, IkappaBalpha. IkappaBalpha degradation requires phosphorylation by IkappaB kinase, ubiquitination by the SCFbeta-TrCP (Skp1/Cullin1/Fbox beta-transducing repeat-containing protein) ubiquitin ligase, and degradation by the 26S proteasome. We tested the hypothesis that Hsp70 attenuates NF-kappaB activation at multiple points in the IkappaBalpha degradative pathway. DESIGN: Laboratory investigation. SETTING: University medical center research laboratory. SUBJECTS: Adolescent (200 g) Sprague-Dawley rats and murine lung epithelial-12 cells in culture. INTERVENTIONS: Lung injury was induced in rats via cecal ligation and double puncture. Thereafter, animals were treated with intratracheal injection of 1) phosphate buffer saline, 2) AdHSP, or 3) an adenovirus expressing green fluorescent protein. Murine lung epithelial-12 cells were stimulated with tumor necrosis factor-alpha and transfected. NF-kappaB was examined using molecular biological tools. MEASUREMENTS AND MAIN RESULTS: Intratracheal administration of AdHSP to rats with cecal ligation and double puncture limited nuclear translocation of NF-kappaB and attenuated phosphorylation of IkappaBalpha. AdHSP treatment reduced, but did not eliminate, phosphorylation of the beta-subunit of IkappaB kinase. In vitro kinase activity assays and gel filtration chromatography revealed that treatment of sepsis-induced lung injury with AdHSP induced fragmentation of the IkappaB kinase signalosome. This stabilized intermediary complexes containing IkappaB kinase components, IkappaBalpha, and NF-kappaB. Cellular studies indicate that although ubiquitination of IkappaBalpha was maintained, proteasomal degradation was impaired by an indirect mechanism. CONCLUSIONS: Treatment of sepsis-induced lung injury with AdHSP limits NF-kappaB activation. This results from stabilization of intermediary NF kappaB/IkappaBalpha/IkappaB kinase complexes in a way that impairs proteasomal degradation of IkappaBalpha. This novel mechanism by which Hsp70 attenuates an intracellular process may be of therapeutic value. PMID- 17855827 TI - Attenuating burn wound inflammation improves pulmonary function and survival in a burn-pneumonia model. AB - OBJECTIVE: We previously showed that topical inhibition of inflammatory signaling in burn wounds reduced systemic inflammatory response and burn-induced pulmonary inflammation. We hypothesized that this topical intervention would attenuate burn induced lung injury, improve pulmonary function, protect lungs from bacterial invasion, and reduce mortality. DESIGN: Controlled, in vivo, laboratory study. SETTING: University laboratory. SUBJECTS: Female mice, 8-10 wks old. INTERVENTIONS: Animals received 30% total body surface area burn followed by topical application of a specific inhibitor of p38 mitogen-activated protein kinase, a key inflammatory signaling pathway, or vehicle to the wound. Twenty four hours after injury, pulmonary collagen deposition and pulmonary function were assessed. One day postburn, some of the animals received intratracheal instillation of Klebsiella pneumoniae and were subsequently monitored for 7 days. MEASUREMENTS AND MAIN RESULTS: Topical inhibition of p38 mitogen-activated protein kinase significantly decreased pulmonary collagen deposition and prevented a decline in pulmonary function at 1 day after burn injury. Compared with sham controls, animals with burn injury had a significantly higher mortality in response to intratracheal bacterial challenge. Application of p38 mitogen activated protein kinase inhibitor to the burn wound attenuated pulmonary neutrophil infiltration and reduced the mortality rate to a level experienced by sham controls. CONCLUSIONS: Inflammatory source control in burn wounds with topical p38 mitogen-activated protein kinase inhibition attenuates acute lung injury, avoids pulmonary dysfunction, protects lungs from bacterial challenge, and improves survival. PMID- 17855828 TI - Effects of epinephrine and vasopressin on cerebral microcirculatory flows during and after cardiopulmonary resuscitation. AB - OBJECTIVES: Both epinephrine and vasopressin increase aortic and carotid arterial pressure when administered during cardiopulmonary resuscitation. However, we recently demonstrated that epinephrine reduces cerebral cortical microcirculatory blood flow. Accordingly, we compared the effects of nonadrenergic vasopressin with those of epinephrine on cerebral cortical microvascular flow together with cortical tissue Po2 and Pco2 as indicators of cortical tissue ischemia. DESIGN: Randomized, prospective animal study. SETTING: University-affiliated research laboratory. SUBJECTS: Domestic pigs. MEASUREMENTS AND MAIN RESULTS: The tracheae of ten domestic male pigs, weighing 40 +/- 2 kg, were noninvasively intubated, and the animals were mechanically ventilated. A frontoparietal bilateral craniotomy was created. Microcirculatory blood flow was quantitated with orthogonal polarization spectral imaging. Blood flow velocity in pial and cortical penetrating vessels measuring <20 microm was graded from 0 (no flow) to 3 (normal). Cerebral cortical tissue carbon dioxide and oxygen tensions (Pbco2 and Pbo2) were measured concurrently using miniature optical sensors. Ventricular fibrillation, induced with an alternating current delivered to the right ventricular endocardium, was untreated for 3 mins. Animals were then randomized to receive central venous injections of equipressor doses of epinephrine (30 microg/kg) or vasopressin (0.4 units/kg) at 1 min after the start of cardiopulmonary resuscitation. After 4 mins of cardiopulmonary resuscitation, defibrillation was attempted. Spontaneous circulation was restored in each animal. However, postresuscitation microvascular flows and Pbo2 were greater and Pbco2 less after vasopressin when compared with epinephrine. We observed that a significantly greater number of cortical microvessels were perfused after vasopressin. CONCLUSIONS: Cortical microcirculatory blood flow was markedly reduced after epinephrine, resulting in a greater severity of brain ischemia after the restoration of spontaneous circulation in contrast to the more benign effects of vasopressin. PMID- 17855829 TI - Succinate recovers mitochondrial oxygen consumption in septic rat skeletal muscle. AB - OBJECTIVE: Mitochondrial dysfunction, particularly affecting complex I of the respiratory chain, could play a fundamental role in the development of multiple organ failure during sepsis. Increasing electron flow through complex II by addition of succinate may improve mitochondrial oxygen utilization and thus adenosine triphosphate production. DESIGN: Ex vivo animal study. SETTING: University research laboratory. SUBJECTS: Male adult Wistar rats. INTERVENTIONS: Fecal peritonitis was induced in conscious, fluid-resuscitated, hemodynamically monitored rats. Sham-operation and naive animals acted as controls. At 48 hrs, clinical severity was graded. Soleus muscle was taken for measurement of mitochondrial complex activities and oxygen consumption. The effect of glutamate plus malate (complex I substrates) and succinate (complex II substrate) on mitochondrial respiration was assessed. MEASUREMENTS AND MAIN RESULTS: In the presence of glutamate plus malate, mitochondrial oxygen consumption was abnormally low in skeletal muscle tissue from moderately-to-severely septic animals as compared with naive and sham-operation controls (both p < .01). On addition of succinate, mitochondrial respiration was augmented in all groups, particularly in moderately-to-severely septic animals (39% +/- 6% increase) as compared with naive (11% +/- 5%; p < .01) and sham-operation controls (10% +/- 5%; p < .01). In the presence of succinate, mitochondrial oxygen consumption was similar between the groups. CONCLUSIONS: Succinate increases mitochondrial oxygen consumption in ex vivo skeletal muscle taken from septic animals, bypassing the predominant inhibition occurring at complex I. This warrants further exploration in vivo as a putative therapeutic modality. PMID- 17855830 TI - The Duffy antigen receptor for chemokines in acute renal failure: A facilitator of renal chemokine presentation. AB - OBJECTIVE: Acute renal failure remains a major challenge in critical care medicine. Both neutrophils and chemokines have been proposed as key components in the development of acute renal failure. Although the Duffy antigen receptor for chemokines (DARC) is present in several tissues and a highly specific ligand for various chemokines, its exact role in vivo remains unclear. DESIGN: Prospective, controlled experimental study. SETTING: University-based research laboratory. SUBJECTS: C57BL/6 wild-type and DARC gene-deficient mice (DARC-/-). INTERVENTIONS: To unravel the functional relevance of DARC in vivo, we compared wild-type and DARC-/- using neutrophil-dependent models of acute renal failure, induced by either local (renal ischemia-reperfusion) or systemic (endotoxemia, lipopolysaccharide) injury. MEASUREMENTS AND MAIN RESULTS: Plasma creatinine and blood urea nitrogen concentrations served as indicators of renal function or dysfunction. Enzyme-linked immunosorbent assays were used to measure tissue and plasma chemokine concentrations. We also performed immunostaining to localize chemokine expression and flow cytometry to evaluate neutrophil recruitment into the kidney. Following renal injury, wild-type mice developed moderate renal ischemia-reperfusion(lipopolysaccharide, 300% increase in plasma creatinine concentrations) to severe acute renal failure (renal ischemia-reperfusion, 40% mortality) as well as extensive renal neutrophil recruitment. DARC-/- mice exhibited no renal dysfunction (renal ischemia-reperfusion) or only very mild renal dysfunction (lipopolysaccharide, 20% increase in serum creatinine concentrations). DARC-/- mice showed no postischemic neutrophil infiltration. Although DARC-/- and wild-type mice exhibited similar global renal neutrophil recruitment during endotoxemia, DARC-/- mice showed significantly impaired neutrophil extravasation. Total renal concentrations of the chemokine macrophage inflammatory protein 2, which has been shown to bind to DARC and to be crucial in postischemic acute renal failure, were either identical (lipopolysaccharide) or only moderately different (renal ischemia-reperfusion) between wild-type and DARC /- mice. Immunostaining revealed an absence of macrophage inflammatory protein-2 in renal endothelial cells of DARC-/- mice. CONCLUSIONS: We suggest that DARC predominantly exerts its effects by controlling spatial chemokine distribution, which in turn regulates neutrophil recruitment and subsequent acute renal failure. PMID- 17855832 TI - Abstracts of the 5th Quebec International Symposium on Cardiopulmonary Prevention and Rehabilitation, Quebec City, Canada, June 13-15, 2007. PMID- 17855831 TI - Vascular endothelial growth factor promotes physical wound repair and is anti apoptotic in primary distal lung epithelial and A549 cells. AB - OBJECTIVE: There is evidence to suggest a beneficial role for growth factors, including vascular endothelial growth factor (VEGF), in tissue repair and proliferation after injury within the lung. Whether this effect is mediated predominantly by actions on endothelial cells or epithelial cells is unknown. This study tested the hypothesis that VEGF acts as an autocrine trophic factor for human adult alveolar epithelial cells and that under situations of pro apoptotic stress, VEGF reduces cell death. DESIGN: In vitro cell culture study looking at the effects of 0.03% H2O2 on both A549 and primary distal lung epithelial cells. MEASUREMENT AND MAIN RESULTS: Primary adult human distal lung epithelial cells express both the soluble and membrane-associated VEGF isoforms and VEGF receptors 1 and 2. At physiologically relevant doses, soluble VEGF isoforms stimulate wound repair and have a proliferative action. Specific receptor ligands confirmed that this effect was mediated by VEGF receptor 1. In addition to proliferation, we demonstrate that VEGF reduces A549 and distal lung epithelial cell apoptosis when administered after 0.03% H2O2 injury. This effect occurs due to reduced caspase-3 activation and is phosphatidylinositol 3'-kinase dependent. CONCLUSION: In addition to its known effects on endothelial cells, VEGF acts as a growth and anti-apoptotic factor on alveolar epithelial cells. VEGF treatment may have potential as a rescue therapy for diseases associated with alveolar epithelial damage such as acute respiratory distress syndrome. PMID- 17855833 TI - Permissive range of hypercapnia for improved peripheral microcirculation and cardiac output in rabbits. AB - OBJECTIVES: Permissive hypercapnia improves outcomes in patients with respiratory failure, most likely because of a reduction in ventilator-induced lung injury. Because hypercapnia is a potent vasoactive stimulus, adequate tissue perfusion and oxygen delivery to dilated microvessels may be restored. We examined how Paco2 affects microvascular changes, hemodynamics, and cardiac output in rabbits. We evaluated the permissive range of Paco2 required for maintenance of the peripheral circulation. DESIGN: Prospective experimental animal study. SETTING: Animal research laboratory. SUBJECTS: A total of 31 Japanese domestic white rabbits. INTERVENTIONS: The animals were anesthetized with pentobarbital. An ear chamber was prepared to examine blood vessels by intravital microscopy. The rabbits were mechanically ventilated with air, oxygen, and CO2. The values of Paco2 were adjusted to about 20 (hypocapnia), 40 (normocapnia), 60, 80, 100, 125, 150, and >250 mm Hg (hypercapnia). After stabilization at each Paco2 level, microvascular changes were recorded with a microscope-closed video camera to permit analysis of arteriolar diameter and blood flow. MEASUREMENTS AND MAIN RESULTS: The pH and heart rate decreased and mean blood pressure increased progressively as the Paco2 was increased. When Paco2 was increased from 20 to 80 mm Hg, vessel diameter, blood-flow velocity, and blood-flow rate increased markedly. Cardiac output increased slightly. When Paco2 exceeded 100 mm Hg, all of these variables decreased. When Paco2 exceeded 150 mm Hg, all variables were significantly lower than the control values (p < .01). CONCLUSION: Intravital microscopic visualization of the rabbit ear microcirculation showed that 150 mm Hg is the permissive upper limit of acute hypercapnia with respect to maintenance of the peripheral microcirculation. PMID- 17855834 TI - Reduction of gap and adherens junction proteins and intercalated disc structural remodeling in the hearts of mice submitted to severe cecal ligation and puncture sepsis. AB - OBJECTIVE: The present study describes intercalated disc remodeling under both protein expression and structural features in experimental severe sepsis induced by cecal ligation and puncture in mice. DESIGN: Controlled animal study. SETTING: University research laboratory. SUBJECTS: Male C57BL/6 mice. INTERVENTIONS: Mice were submitted to moderate and severe septic injury by cecal ligation and puncture. MEASUREMENT AND MAIN RESULTS: Severe septic injury was accompanied by a large number of bacteria in the peritoneal cavity and blood, high levels of tumor necrosis factor-alpha, and monocyte inflammatory protein-1alpha in the septic focus and serum, marked hypotension, and a high mortality rate. Western blot analysis and immunofluorescence showed a marked decrease of key gap and adherens junction proteins (connexin43 and N-cadherin, respectively) in mice submitted to severe septic injury. These changes may result in the loss of intercalated disc structural integrity, characterized in the electron microscopic study by partial separation or dehiscence of gap junctions and adherens junctions. CONCLUSIONS: Our data provide important insight regarding the alterations in intercalated disc components resulting from severe septic injury. The intercalated disc remodeling under both protein expression and structural features in experimental severe sepsis induced by cecal ligation and puncture may be partly responsible for myocardial depression in sepsis/septic shock. Although further electrophysiological studies in animals and humans are needed to determine the effect of these alterations on myocardial conduction velocity, the abnormal variables may emerge as therapeutic targets, and their modulation might provide beneficial effects on future cardiovascular outcomes and mortality in sepsis. PMID- 17855835 TI - Antioxidant treatment prevented late memory impairment in an animal model of sepsis. AB - OBJECTIVE: Assess the effect of antioxidant treatment on late memory impairment and early hippocampus oxidative stress after cecal ligation and perforation. SUBJECTS: Male Wistar rats. INTERVENTIONS: Rats underwent sham operation or cecal ligation and perforation. Animals that underwent cecal ligation and perforation were divided into groups: 1) treated with basic support (50 mL/kg saline, 30 mg/kg ceftriaxone, and 25 mg/kg clindamycin every 6 hrs), 2) treated with basic support plus N-acetylcysteine (20 mg/kg N-acetylcysteine at 3, 6, 12, 18, and 24 hrs after cecal ligation and perforation), 3) treated with basic support plus deferoxamine (20 mg/kg deferoxamine at 3 and 24 hrs after cecal ligation and perforation), 4) treated with basic support plus N-acetylcysteine and deferoxamine, or 5) treated with N-acetylcysteine plus deferoxamine. MEASUREMENTS AND MAIN RESULTS: On days 10 and 30 after surgery, the animals underwent behavioral tasks: inhibitory avoidance task, habituation to an open field, and continuous multiple-trials step-down inhibitory avoidance task. The sepsis group showed significantly decreased performance in latency retention compared with the sham group in the inhibitory avoidance task. In the open-field task, the sepsis group presented memory impairment after sepsis. In the continuous multiple-trials step-down inhibitory avoidance task, the sepsis group showed a significant increase in the number of training trials required to reach the acquisition criterion. All these memory impairments were prevented by N-acetylcysteine plus deferoxamine treatment, but not its isolate use. In addition, the combined use of antioxidants attenuated oxidative damage in hippocampus 6 hrs after sepsis induction. CONCLUSIONS: Antioxidant treatment prevented the development of late cognitive deficits in an animal model of sepsis. PMID- 17855836 TI - Disseminated intravascular coagulation. AB - OBJECTIVE: To review the current knowledge on the clinical manifestation, pathogenesis, diagnosis, and management of disseminated intravascular coagulation (DIC). DATA SOURCE: Selected articles from the MEDLINE database. DATA SYNTHESIS: DIC may complicate a variety of disorders and can cause significant morbidity (in particular related to organ dysfunction and bleeding) and may contribute to mortality. The pathogenesis of DIC is based on tissue factor-mediated initiation of systemic coagulation activation that is insufficiently contained by physiologic anticoagulant pathways and amplified by impaired endogenous fibrinolysis. The diagnosis of DIC can be made using routinely available laboratory tests and scoring algorithms. Supportive treatment of DIC may be aimed at replacement of platelets and coagulation factors, anticoagulant treatment, and restoration of anticoagulant pathways. CONCLUSIONS: Insight into the pathogenesis of DIC has resulted in better strategies for clinical management, including straightforward diagnostic criteria and potentially beneficial supportive treatment options. PMID- 17855837 TI - Effects of hypothermia on drug disposition, metabolism, and response: A focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system. AB - OBJECTIVES: Therapeutic hypothermia has been shown to decrease neurologic damage in patients experiencing out-of-hospital cardiac arrest. In addition to being treated with hypothermia, critically ill patients are treated with an extensive pharmacotherapeutic regimen. The effects of hypothermia on drug disposition increase the probability for unanticipated toxicity, which could limit its putative benefit. This review examines the effects of therapeutic hypothermia on the disposition, metabolism, and response of drugs commonly used in the intensive care unit, with a focus on the cytochrome P450 enzyme system. DATA SOURCES AND STUDY SELECTION: A MEDLINE/PubMed search from 1965 to June 2006 was conducted using the search terms hypothermia, drug metabolism, P450, critical care, cardiac arrest, traumatic brain injury, and pharmacokinetics. DATA EXTRACTION AND SYNTHESIS: Twenty-one studies were included in this review. The effects of therapeutic hypothermia on drug disposition include both the effects during cooling and the effects after rewarming on drug metabolism and response. The studies cited in this review demonstrate that the addition of mild to moderate hypothermia decreases the systemic clearance of cytochrome P450 metabolized drugs between approximately 7% and 22% per degree Celsius below 37degreesC during cooling. The addition of hypothermia decreases the potency and efficacy of certain drugs. CONCLUSIONS: This review provides evidence that the therapeutic index of drugs is narrowed during hypothermia. The magnitude of these alterations indicates that intensivists must be aware of these alterations in order to maximize the therapeutic efficacy of this modality. In addition to increased clinical attention, future research efforts are essential to delineate precise dosing guidelines and mechanisms of the effect of hypothermia on drug disposition and response. PMID- 17855838 TI - Conflicts of interest in research: how IRBs address their own conflicts. PMID- 17855839 TI - Evaluating the risks and benefits of phase II and III cancer clinical trials: a look at Institutional Review Board members in the Netherlands. PMID- 17855840 TI - The cat conundrum. PMID- 17855841 TI - [To whom diving should be permitted]. PMID- 17855842 TI - [Diagnosis of decompression sickness. Warning signal: aches and abnormal fatigue]. PMID- 17855843 TI - [When children do not want to speak]. PMID- 17855844 TI - [Living kidney donation--selection criteria for the donor]. AB - In Germany, the average waiting time for a kidney is between five and six years. Living kidney donation has a unique status among the various alternatives for shortening the waiting list. The frequency of living kidney donations has increased from 3.9% in 1993 to 19.1% in 2005. The German transplantation law of 1997 permits living kidney donation as a possibility if a suitable organ from a deceased donor is not available at the time of organ removal. Organs from living persons that are suitable for donation include primarily the kidney, but also parts of the liver, the lung and sometimes also the small intestine. The continuously improving immunosuppressive treatment procedures in the meantime have made transplantation to recipients with increased risk also possible. PMID- 17855845 TI - [Results of increasing competition. Medical practices and physician associations have to adapt]. PMID- 17855846 TI - Re: Antao B and MacKinnon AE. Axial fixation of testes for prevention of recurrent testicular torsion. 2006 Surgeon 4:1; 20-21. PMID- 17855847 TI - A Greek summer tragedy. PMID- 17855848 TI - Germany goes for solar. PMID- 17855849 TI - Questions on biofuels. PMID- 17855850 TI - Democracy runs deep. PMID- 17855851 TI - Armand Leroi. PMID- 17855852 TI - Humboldt expansion. PMID- 17855853 TI - Words of wisdom. Re: feasibility of the use of phosphodiesterase type 5 inhibitors in a pharmacologic prevention program for recurrent priapism. PMID- 17855854 TI - Words of wisdom. Re: detection of circulating urothelial cancer cells in the blood using the CellSearch system. PMID- 17855855 TI - Words of wisdom. Re: genome-wide association study of prostate cancer identifies a second risk locus at 8q24. PMID- 17855856 TI - Words of wisdom. Re: prostate-specific antigen (PSA) and PSA velocity for prostate cancer detection in men aged <50 years. PMID- 17855857 TI - Proceedings of the Fifth International Symposium on Pneumococci and Pneumococcal Diseases. Alice Springs, Central Australia. April 2-6, 2006. PMID- 17855858 TI - Words of wisdom. Re: detection of life-threatening prostate cancer with prostate specific antigen velocity during a window of curability. PMID- 17855859 TI - Comparing survival outcomes for patients with colorectal cancer treated in public and private hospitals. PMID- 17855860 TI - [The role of carbapenems in combined therapy of patients with common forms of peritonitis]. PMID- 17855861 TI - Psychiatry in pictures. PMID- 17855862 TI - [Establishment as a surgeon--opportunity with risk]. PMID- 17855863 TI - [Quality management in surgical practice. Why quality in medical care?]. PMID- 17855864 TI - [BDC statute changes from the viewpoint of the established surgeon]. PMID- 17855865 TI - [Does hospitalist medical care have a future?]. PMID- 17855866 TI - [Ambulatory surgery--a description of current status]. PMID- 17855867 TI - [GOA: BGH validates BAK guidelines for hallux valgus surgery]. PMID- 17855868 TI - [Closure of the surgical department--shut down despite assumption of personnel and equipment by neighboring hospital?]. PMID- 17855869 TI - [Regulation for improving economics in drug treatment]. PMID- 17855871 TI - [Health care reform: cutting back on surplus in the system]. PMID- 17855872 TI - [New alliance of independent physician associations established]. PMID- 17855873 TI - [The basic surgery examination--a first step in structured graduate education]. PMID- 17855874 TI - [The communication in group practices, practice associations and MVZs. Preventing conflict as the basis for constructive cooperation]. PMID- 17855875 TI - [Women physicians in the university surgery -- situation in the year 2006]. PMID- 17855876 TI - [The family-friendly hospital as wish workplace]. PMID- 17855877 TI - [Child care in the clinic -- economically a good decision]. PMID- 17855878 TI - [Women physicians do not leave their life- and professional career to chance]. PMID- 17855879 TI - [ICD-10 and OPS: relevant changes for surgery from 2007]. PMID- 17855880 TI - [The GKV-competition strengthening law]. PMID- 17855881 TI - [Tension field between guidelines and health economics. Guideline work as integral constant part of medical quality management]. PMID- 17855882 TI - [Do women and men communicate basically differently?]. PMID- 17855883 TI - ["I was curious how communication in surgery can be imparted?"]. PMID- 17855884 TI - [HIV-test in blood donation]. PMID- 17855885 TI - [Cost assumption for continuing education institutions]. PMID- 17855886 TI - [Virus infections (for example HCV, HIV etc.). Compensation rules during activity restrictions or- prohibition]. PMID- 17855887 TI - [Experiences in the planning and carrying out of previous expert seminars]. PMID- 17855888 TI - [Surgery in system change]. PMID- 17855889 TI - [Delegation of surgical activities to nonphysician assistant personnel. Statement of the Professional Union of German Surgeons]. PMID- 17855890 TI - [Renewed joint statement of the Professional Union of German Anesthetists (BDA) and the German Anesthesiology and Intensive Medicine Society (DGAI) concerning permissiveness and limitations of parallel procedures in anesthesiology ("Munster Declaration II 2007"]. PMID- 17855891 TI - [Capabilities of delegation of physicians' performances to nonphysician personnel]. PMID- 17855892 TI - [DRG exercises: Conservative and surgical treatment of humeral head fractures]. PMID- 17855893 TI - [Personnel planning and position calculation on the basis of InEK data]. PMID- 17855894 TI - [Joint recommendations of the German Society of Anesthesiology and Intensive Medicine and the Professional Union of German Anesthetists as well as the German Society of Surgery and the Professional Union of German Surgeons concerning the design and organization of interdisciplinary surgical intensive units (ISU)]. PMID- 17855895 TI - [Structured continuing surgery education and establishing of log books]. PMID- 17855896 TI - [Everybody speaks about coaching....]. PMID- 17855897 TI - [Transition determinations concerning the acquiring of the new specialist physician designation "Orthopedics and Accident Surgery"]. PMID- 17855898 TI - [Joint Continuing Education Organization of the BDC Lower Saxony and Bremen in cooperation with the ANC and BVO Lower Saxony in Hannover on 2/10/2007]. PMID- 17855899 TI - [New forms of health care]. PMID- 17855900 TI - [DRG practice: colon surgery]. PMID- 17855901 TI - [Integrated care--the heart of a viable future health care system]. PMID- 17855902 TI - [Integrated health care in trauma surgery]. PMID- 17855903 TI - [Surgical practice in an integrated physician network]. PMID- 17855904 TI - [Possibilites of new health care structures in ambulatory surgery]. PMID- 17855905 TI - [As surgeon in a large integrated medical care center]. PMID- 17855906 TI - [Medical care center and integrated health care contracts--quo vadis surgery?]. PMID- 17855907 TI - [Evaluation and future of integrated health care]. PMID- 17855908 TI - [May services with insufficient reimbursement be denied to German public health insurance patients, while they are offered to patients with private insurance?]. PMID- 17855909 TI - [Tax relevant organization of incomes of physician executives from the proceeds of autonomous medical services]. PMID- 17855911 TI - [Where is promised autonomy?]. PMID- 17855912 TI - [Concept of a new medical fee regulation]. PMID- 17855913 TI - [The physician-patient relationship in an economically founded health care system]. PMID- 17855916 TI - [Leasing is cost effective]. PMID- 17855917 TI - [Modern "leadership" in hospitals]. PMID- 17855918 TI - [DRG practice: gastrointestinal hemorrhage--case summary]. PMID- 17855919 TI - [Lenin and the contract physician]. PMID- 17855920 TI - [Organizational liabilities in the clinic and general practice--medical standards in structural and organizational changes. Einbecker recommendations of the German Society of Medical Law (DGMR) e.V]. PMID- 17855921 TI - [Current professional policy 06/2006]. PMID- 17855922 TI - [Young surgeons--what us the work situation in Europe?]. PMID- 17855923 TI - [Evaluating the "Surgery Quality Seal" (CQS), a new method of continuous professional development of surgeons, by participants. Results of a pilot study]. PMID- 17855924 TI - [Effective "communication with one another" in professional routine]. PMID- 17855925 TI - [Life satisfaction of graduates in medicine]. PMID- 17855926 TI - [Graduate education in surgery is the future]. PMID- 17855927 TI - [The surgery assistant in graduate education. Personal requirements and expectations of graduate education faculty and graduate education schools]. PMID- 17855928 TI - [Graduate education as ongoing (survival) responsibility in surgery]. PMID- 17855929 TI - [Continuous training laboratory of a large surgical teaching clinic--the Marburg Surgical Training Laboratory "MaCh"!]. PMID- 17855930 TI - [Model of structured continuing and graduate education in the surgery specialty]. PMID- 17855931 TI - [Advanced education in trauma surgery is still not standardized]. PMID- 17855932 TI - [Log book and performance documentation in graduate surgery education]. PMID- 17855933 TI - ["Complex treatments" in surgery--new approaches in performance adjusted DRG reimbursment of expensive treatments]. PMID- 17855934 TI - [Recent developments in the official fee regulation for physicians]. PMID- 17855935 TI - [Change in the contract physician rights regulation. Parliamentary deliberations continue]. PMID- 17855936 TI - [4th National Protest Day. For physician autonomy--against public health reform]. PMID- 17855937 TI - [Structured procedure in peer communication. Effective "communicating with one another" in professional routine]. PMID- 17855938 TI - [Modern leadership--what is important. BDC seminar in physician leadership]. PMID- 17855939 TI - Larvicidal algae. AB - Although most algae are nutritious food for mosquito larvae, some species kill the larvae when ingested in large quantities. Cyanobacteria (blue-green algae) that kill larvae do so by virtue of toxicity. While blue-green algae toxins may offer possibilities for delivery as larvicides, the toxicity of live blue-green algae does not seem consistent enough for live algae to be useful for mosquito control. Certain species of green algae in the order Chlorococcales kill larvae primarily because they are indigestible. Where these algae are abundant in nature, larvae consume them to the exclusion of other food and then starve. Under the right circumstances, it is possible to introduce indigestible algae into a breeding habitat so they become abundant enough to render it unsuitable for mosquito production. The algae can persist for years, even if the habitat dries periodically. The main limitation of indigestible algae lies in the fact that, under certain conditions, they may not replace all the nutritious algae in the habitat. More research on techniques to ensure complete replacement will be necessary before indigestible algae can go into operational use for mosquito control. PMID- 17855940 TI - Follow up after PEG tube insertion. PMID- 17855941 TI - [Stem cell niches]. AB - The nature of the stem cell niche and its interaction with stem cells is one of fundamental problems in the biology of stem cells. Stem cell niches are formed during ontogeny. A niche can remain vacant and exist independently of stem cells; however, stem cell self-renewal cannot be maintained for long periods outside of the niche except for particular conditions, e.g., in vitro. A vacant niche can be occupied by excessive or transplanted stem cells and can provide for their functioning. A niche size allows a definite number of stem cells to be maintained. Excessive stem cells either differentiate in the presence of a specific signal or undergo apoptosis in the absence of such signal. Thus, the niches control the number of stem cells in the body and protect it from excessive stem cell proliferation. Under particular conditions, stem cells can leave and return to their niches. Stem cells are retained in the niche by cell-to-cell interactions and adhesion to the extracellular matrix. Both the niches and stem cells arise at a particular ontogenetic stage and are capable of long self renewal. The development can be described in terms of the formation of stem cells and their niches. PMID- 17855942 TI - AHA sees $11.1 million profit. Investments, member dues contribute to bottom line. PMID- 17855943 TI - Leapfrog's next move. Delbanco leaving quality group in transition. PMID- 17855944 TI - Worst-case scenario. Many hospitals still unprepared for disaster: CDC. PMID- 17855945 TI - CMS: your mistake, your problem. Eight hospital-acquired conditions won't be paid for. PMID- 17855946 TI - Novant takes on imaging. System buying MedQuest as for-profit subsidiary. PMID- 17855947 TI - Give payers EHR data: report. Privacy, security advocates oppose fraud fighting' plan. PMID- 17855948 TI - I. On Removal (by scraping out) of the Marrow of long Bones, and especially on this proceeding as a Treatment of Osteo-myelitis; also on the same followed by the local application of Corrosive Sublimate Solution and of Iodoform. PMID- 17855949 TI - III. An Inquiry into the Use of the Ligature in the Treatment of Aneurysm. PMID- 17855951 TI - I. Annus Chirurgicus-1884. PMID- 17855950 TI - IV. A successful case of Laparo-elytrotomy, with remarks on the operation. PMID- 17855952 TI - I. New York Surgical Society. PMID- 17855953 TI - Stated Meeting, October 28, 1884. PMID- 17855954 TI - II. Treatment of Wounds of the Anterior Tibial Artery complicating Compound Fracture of the Leg; with Report of a Case. PMID- 17855955 TI - Index of Surgical Progress. PMID- 17855956 TI - I. On the Use of Vulcanized Rubber in Surgical Instruments. PMID- 17855958 TI - III. A Case of Attempted Radical Cure for Hernia; Haemorrhage; Abdominal Section; Death on the Fourth Day; with Remarks. PMID- 17855957 TI - II. Congenital Sacral Cysts. Description of a Case, with Remarks. PMID- 17855959 TI - IV. Two Cases of Malignant Lymphoma, with Remarks. PMID- 17855960 TI - I. On the Dangers of Modern Operative Proceedings for the Radical Cure of Hernia. PMID- 17855961 TI - II. Recent Contributions to the Surgery of the Nerves. PMID- 17855962 TI - III. Tracheotomy in Laryngeal Stenosis of Tuberculous Origin. PMID- 17855964 TI - I. Society of German Scientists and Physicians. PMID- 17855963 TI - IV. Passavant on Tracheotomy for Diphtheritic Croup. PMID- 17855965 TI - II. Society of Surgery of Paris: Sessions from October 1 to 15, 1884. PMID- 17855966 TI - III. New York Surgical Society. PMID- 17855967 TI - INDEX OF SURGICAL PROGRESS. PMID- 17855968 TI - I. Diphtheria and Tracheotomy in Leipsic. PMID- 17855969 TI - I. Statistical Contribution to Cerebral Surgery. PMID- 17855970 TI - I. Tuberculous Surgical Affections. PMID- 17855971 TI - II. Charcot's Disease. PMID- 17855972 TI - I. London Clinical Society: Charcot's Disease. PMID- 17855973 TI - II. Philadelphia Academy of Surgery: Combined Tubular and Capillary Drainage of Large Wounds. PMID- 17855974 TI - III. New York Surgical Society: Excision of the Entire Tarsus for Tubercular Osteitis. PMID- 17855975 TI - INDEX OF SURGICAL PROGRESS. PMID- 17855976 TI - I. The Mechanism of Fractures of the Clavicle. PMID- 17855977 TI - II. The Local Lesions caused by the Alkaline Salts of Chromic Acid. PMID- 17855978 TI - III. Extirpation of the Kidney. PMID- 17855979 TI - IV. Venous Blood-Tumors of Cranium Communicating with Superior Longitudinal Sinus. PMID- 17855980 TI - V. The Use of Hare-Lip Pins for Fixing the Stomach in Gastrostomy. PMID- 17855981 TI - VI. A Successful Case of Gastrostomy. PMID- 17855983 TI - I. On the Present State of Treatment of Thyroid Tumors. PMID- 17855982 TI - VII. Case of Neurectomy of Infra-orbital Branch of Fifth Nerve. PMID- 17855984 TI - II. On Pneumotomy. PMID- 17855985 TI - INDEX OF SURGICAL PROGRESS. PMID- 17855986 TI - I. Chronic Peri-uterine Abscess, and its Treatment by Laparotomy. PMID- 17855987 TI - II. On a Peculiar Form of Fibrous Tumor, which Tends to Multiplicity and Indefinite Growth. PMID- 17855988 TI - III. The Cure of some Uterine Displacements by Shortening the Round Ligaments. PMID- 17855989 TI - IV. Venous Blood Tumors of the Vault of the Cranium Communicating with the Superior Longitudinal Sinus. Continued. PMID- 17855990 TI - V. Case of Fracture of Femur Complicated with Sacro-iliac Dislocation. PMID- 17855991 TI - VI. Co-aptation Fork for Treating Fractures of the Patella. PMID- 17855992 TI - I. Tuberculous Surgical Affections-The Conditions which Predispose Bone to Tuberculosis. PMID- 17855993 TI - INDEX OF SURGICAL PROGRESS. PMID- 17855994 TI - I. Further Observations on the Treatment of Stone in the Bladder. PMID- 17855995 TI - II. An Experimental and Clinical Study of Air-Embolism. PMID- 17855996 TI - III. Sponge Grafting. PMID- 17855998 TI - INDEX OF SURGICAL PROGRESS. PMID- 17855997 TI - IV. Haemorrhage from the External Auditory Meatus by Erosion of the Internal Carotid Artery; Ligature of Common Carotid; Recovery. PMID- 17855999 TI - I. The Field and Limitation of the Operative Surgery of the Human Brain. PMID- 17856000 TI - II. An Experimental and Clinical Study of Air-Embolism. (Continued.). PMID- 17856001 TI - III. Surgical Observations in the Treatment of the Diseases and Accidents of the Liver. PMID- 17856002 TI - IV. Cases of Surgical Affections of Joints treated with Listerian Antiseptic Precautions. PMID- 17856004 TI - I. Tuberculosis of Glands, and the Importance of Early Operations. PMID- 17856003 TI - V. Case of Compound Depressed Fracture of Skull, with Wound of the Longitudinal Sinus. Note on the Construction of the Trephine. PMID- 17856005 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856006 TI - III. The Field and Limitation of the Operative Surgery of the Human Brain. (Continued.). PMID- 17856007 TI - IV. An Experimental and Clinical Study of Air-Embolism. (Continued.). PMID- 17856008 TI - I. Schede's Results with Corrosive Sublimate as an Antiseptic Surgical Dressing at the Hamburg General Hospital. PMID- 17856009 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856010 TI - I. On certain Obscure Sprains of the Elbow occurring in Young Children. PMID- 17856011 TI - II. On the Surgical Dissemination of Cancer. PMID- 17856012 TI - I. Secondary Nerve Suture. PMID- 17856013 TI - II. Air-Embolism. (Concluded). PMID- 17856014 TI - III. The Field and Limitation of the Operative Surgery of the Human Brain. (Concluded). PMID- 17856015 TI - IV. A Case of Catheter Fever. PMID- 17856017 TI - I. Aneurismal Tumors of the Temporal Region. PMID- 17856016 TI - V. Compound Comminuted Fracture of the Patella: Wire Sutures: Necrosis of Upper Fragment: Final Recovery with Useful Limb. PMID- 17856018 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856019 TI - I. Astragaloid Osteotomy in the Treatment of Flat-Foot. PMID- 17856020 TI - II. Observations upon the Surgical Anatomy of the Kidneys. PMID- 17856022 TI - I. Tuberculous Surgical Affections: Volkmann's Clinical Observations. PMID- 17856021 TI - III. Mooted Points in Syphilology. PMID- 17856023 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856024 TI - I. On Preliminary Ligature of the Lingual Arteries in Excision of the Tongue, With a Report of Three Cases. PMID- 17856025 TI - II. Injuries of the Main Blood-Vessels in the Axilla, Caused by Efforts to Reduce Dislocations of the Shoulder. PMID- 17856027 TI - I. On the Organization of the Surgical Staff in General Hospitals. PMID- 17856026 TI - III. On the Treatment of Epydidymitis by Oil of Yellow Sandal Wood, and on the Mode of Action of that Oil. PMID- 17856028 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856029 TI - I. Papillomatous Cystic Disease of the Broad Ligaments; Its Clinical and Operative Features; With Three Cases. PMID- 17856030 TI - II. A Contribution to the Etiology of Malignant Tumors. PMID- 17856031 TI - III. On Disarticulation at the Hip-Joint, and on a New Mode of Its Performance. PMID- 17856032 TI - I. Landerer's Mechanical Theory of Inflammation. PMID- 17856033 TI - II. The Present Status of the Operation of Extirpation of the Uterus for Malignant Disease. PMID- 17856035 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856034 TI - III. On the Use of Injections of Ethereal Solutions of Iodoform in the Treatment of Cold Abscesses. PMID- 17856036 TI - I. Unilateral Hypertrophy of the Gums, associated with Other Abnormalities, chiefly Hypertrophic and Unilateral. PMID- 17856038 TI - IV. A Case of Total Extirpation of the Larynx. PMID- 17856037 TI - III. On Unilateral Extirpation of the Larynx. PMID- 17856039 TI - V. A Case of Total Extirpation of the Larynx. PMID- 17856040 TI - VI. On Gangrene of the Scrotum After Removal of Enlarged Inguinal Glands. PMID- 17856041 TI - I. On the Present State of Knowledge in Bacterial Science, in Its Surgical Relations. PMID- 17856043 TI - III. Extirpation of the Larynx. PMID- 17856042 TI - II. Cocaine as an Anaesthetic; Its Status at the Close of the First Year of its Use. PMID- 17856044 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856045 TI - II. On Excision of the Hip. PMID- 17856046 TI - I. Arterial Ligation as a Prophylactic Measure after Sudden, Complete and Permanent Occlusion of the Chief Vein at the Root of an Extremity. PMID- 17856047 TI - II. On the Advantages of the Principle of Dry Dressings in Antiseptic Surgery. PMID- 17856048 TI - III. A Case of Deformity of the Fore-Arm and Hands, with an unusual History of Hereditary Congenital Deficiency. PMID- 17856049 TI - IV. A Case of Laparotomy for Intestinal Obstruction-Death. PMID- 17856051 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856050 TI - I. On the Present State of Knowledge in Bacterial Science, in Its Surgical Relations. PMID- 17856052 TI - I. Rupture of the Ligamentum Patellae and its Treatment by Operation. PMID- 17856054 TI - I. Laparotomy for Intestinal Obstruction. PMID- 17856053 TI - II. Excision of the Tarsal Bones. PMID- 17856056 TI - III. On Transfusion and Reinfusion of Blood. PMID- 17856055 TI - II. On the Present State of Knowledge in Bacterial Science in Its Surgical Relations (Continued): Osteomyelitis. PMID- 17856057 TI - IV. Lactic Acid as a Destroyer of Pathogenic Tissue. PMID- 17856058 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856059 TI - I. The Operative Treatment of Facial Neuralgia. PMID- 17856060 TI - I. On the Present State of Knowledge in Bacterial Science in Its Surgical Relations (Continued): Sepsis. PMID- 17856061 TI - II. Rectal Examinations in Cases of Intestinal Obstruction. PMID- 17856062 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856063 TI - I. Lipoma of Testicle. PMID- 17856064 TI - II. Operations for Pyloric Stenosis. PMID- 17856065 TI - III. Cholecystotomy. PMID- 17856066 TI - I. On Laparotomy in Cases of Perforation of the Stomach and Intestines. PMID- 17856067 TI - II. Recent Contributions to the Literature of Cholecystotomy. PMID- 17856069 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856068 TI - III. On the Present State of Knowledge in Bacterial Science in its Surgical Relations (Continued): Pyaemia, Erysipelas. PMID- 17856070 TI - I. On Laparotomy in the Treatment of Strangulated Hernia. PMID- 17856072 TI - III. Report of a Case of Leg Amputation at an Advanced Age, with Recovery: Report of a Case of Exploratory Trephining of Cervical Vertebrae. PMID- 17856071 TI - II. Resection of the Large Intestine for Carcinoma. PMID- 17856073 TI - I. On Stenosis of the Trachea After Tracheotomy for Croup and Diphtheria. PMID- 17856074 TI - II. On the Present State of Knowledge in Bacterial Science in its Surgical Relations (Continued): Micro-Organisms and Suppuration. PMID- 17856075 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856077 TI - II. Urethral Fever. PMID- 17856076 TI - I. Stretching of the Facial Nerve. PMID- 17856078 TI - III. Radical Cure of Hydrocele by Antiseptic Incision. PMID- 17856079 TI - IV. Alexander's Operation of Shortening the Round Ligaments. PMID- 17856080 TI - I. The Treatment of Aneurism by the Introduction of Coagulants. PMID- 17856081 TI - II. Excision of the Hip-Joint. PMID- 17856082 TI - III. On the Present State of Knowledge in Bacterial Science in its Surgical Relations (Continued): Tuburculosis. PMID- 17856083 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856085 TI - III. The Treatment of Fractures of the Lower End of the Radius: with discussion at the New York Surgical Society. PMID- 17856084 TI - II. The Operation for Varicocele. PMID- 17856086 TI - I. On Lateral Pharyngotomy for the Extirpation of Malignant Tumors of the Tonsillar Region. PMID- 17856087 TI - II. The Paris Society of Surgery, and the Question of Operations for Tuberculus Joint Disease. PMID- 17856088 TI - III. On the Present State of Knowledge in Bacterial Science in its Surgical Relations (Continued): Gonorrhoea. PMID- 17856090 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856089 TI - IV. Treatment of Stricture of the Urethra by Electrolysis. PMID- 17856091 TI - I. On the Radical Cure of Oblique Inguinal Hernia by Internal Abdominal Pad and the Restoration of the Valved Form of the Inguinal Canal. PMID- 17856093 TI - I. On Tumors of the Urinary Bladder and their Treatment. PMID- 17856092 TI - I OEsophagotomy for Foreign Bodies Lodged in the Tube. PMID- 17856094 TI - II. On the Present State of Knowledge in Bacterial Science in its Surgical Relations (Concluded): Actinomycosis-Anthrax-Glanders. PMID- 17856095 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856096 TI - I. Excision of the Bones of the Tarsus for Tubercular Disease. PMID- 17856097 TI - II. On the Advantages of Supra-Pubic Lithotomy, with Report of a Case. PMID- 17856098 TI - III. Clinical Observations on Fibro-Myomatous Tumors of the Uterus. PMID- 17856099 TI - I. The Treatment of Compound Fractures of the Skull. PMID- 17856100 TI - II. On the Contagiousness of Leprosy. PMID- 17856101 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856102 TI - I. The Servo-Bulgarian War from a Surgical Point of View. PMID- 17856103 TI - II. An Improved Trocar for Paracentesis Abdominis. PMID- 17856104 TI - I. The Surgical Treatment of Malignant Tumors of the Fauces. PMID- 17856105 TI - II. Excision of the Larynx. PMID- 17856106 TI - III. Osteoclasis. PMID- 17856107 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856108 TI - I. Szymanowski's Operation as Applied to the Cure of Urethro-Perineal Fistula. PMID- 17856110 TI - III. Two Cases of Laparotomy for Perforating Gunshot Wound of the Abdomen, with Fatal Termination. PMID- 17856109 TI - II. A Second Case of Recovery from Perforating Gun-Shot Wound of the Abdomen, through Laparotomy and Suture of Intestinal Abscess. PMID- 17856111 TI - IV. Results of Antiseptic Methods in the Treatment of Wounds as shown in a series of 100 Consecutive Operations. PMID- 17856113 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856112 TI - I. Operative Attacks upon the Human Brain. PMID- 17856114 TI - I. On Nephrolithotomy, with Report of a Case. PMID- 17856115 TI - III. Wound of Large Irregular Vein-Trunk in Groin. PMID- 17856116 TI - IV. Radical Cure of Hernia-Cirrhosis of Penis. PMID- 17856117 TI - I. The Surgical Treatment of Peritonitis. PMID- 17856118 TI - II. High-Lying Strictures of the Rectum. PMID- 17856119 TI - III. Osteoclasis (concluded). PMID- 17856120 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856121 TI - II. The Treatment of Wound after Castration. PMID- 17856122 TI - II. Note on Amputation for Joint-Disease when Lung Tuberculosis Coexists. PMID- 17856123 TI - III. Abnormalities of the Urachus. PMID- 17856124 TI - I. The Pathology of Peritonitis. PMID- 17856126 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856125 TI - II. Gastrotomy for Foreign Bodies. PMID- 17856127 TI - I. On the Meaning of the Reverse in Bandaging. PMID- 17856128 TI - I. On the Pathology of Transverse Fractures of the Patella and Olecranon: Showing the Chief Cause of Non-Osseous Union in these Fractures and how to Obviate it. PMID- 17856129 TI - II. On the Treatment of Inveterate Talipes Equino-Varus by Osteotomy. PMID- 17856131 TI - III. The Discussion on the Surgery of the Liver at the 1886 Meeting oe the British Medical Association. PMID- 17856130 TI - I. The Surgery of the Liver. PMID- 17856132 TI - II. Results of Socin's Operations for the Radical Gure oe Hernia at the Bale Clinic. PMID- 17856133 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856134 TI - I. Notes on the Surgical Treatment of Affections of the Kidney. PMID- 17856135 TI - II. On the Use and Abuse of Passive Motion. PMID- 17856136 TI - III. Plastic Operation for Closure of a Large Laryngeal Fistula. PMID- 17856137 TI - IV. Case of Rupture of Gall Bladder; Cholecystotomy; Subsequent Obstruction of Common Bile Duct by Overlooked Impacted Calculus; Death. PMID- 17856138 TI - I. Schuchardt on the Indications for the Excision of Joints After Gunshot Wounds. PMID- 17856139 TI - II. Senn on the Surgery of Pancreas. PMID- 17856140 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856141 TI - I. The Surgery of the Lungs. PMID- 17856142 TI - II. The Treatment of Fractured Patella. PMID- 17856143 TI - III. Dislocations of Acromial End of the Clavicle directly backwards. PMID- 17856144 TI - IV. The String Drain. PMID- 17856146 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856145 TI - V. Digital Amputations under Cocaine. PMID- 17856147 TI - I. Should Laparotomy be Done For Penetrating Gunshot Wounds of the Abdomen, Involving he Viscera. PMID- 17856149 TI - III. Four Months of Opera[ill]ive Work at the New York Hospital. PMID- 17856148 TI - II. Contributions to Intestinal and Anal Surgery: Inguinal Colotomy-Excision of Hemorrhoids-Excision of Fistulae in Ano-New Operation for Cure of Prolapsus Ani. PMID- 17856150 TI - I. Wire Suturing of Fracture of the Patella as an Immediate Method of Treatment. PMID- 17856151 TI - II. Cure of Haemorrhoids by Excision. PMID- 17856152 TI - III. Kronlein on the Operative Treatment of Acute Diffuse Putrid Purulent Peritonitis. PMID- 17856153 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856154 TI - I. On Thyroidectomy: Remarks on the Operation, With a Report of Four Successful Cases. PMID- 17856155 TI - III. OEsophagotomy: Remarks on the Operation, With Report of a Case. PMID- 17856157 TI - V. Report of Four Month's Operative Work at the New York Hospital (concluded). PMID- 17856156 TI - IV. Abnormal Frangibility and Delayed and Non-Union of Fractures of the Long Bones in General Paretics. PMID- 17856158 TI - VI. A Case of Recovery Through Laparotomy for Perforating Pistol-shot Wound of the Abdomen. PMID- 17856159 TI - I. Operative Results in Cases of Tuberculous Disease of the Wrists and of the Testicles. PMID- 17856160 TI - II. The Etiology of Pathological Dislocations. PMID- 17856161 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856162 TI - II. Perineal Urethrotomy: Report of Nine Cases of Perineal Section of the Urethra without a Guide. PMID- 17856163 TI - II. Ligation of the External Carotid Artery: A Synopsis of Five Successful Cases. PMID- 17856164 TI - III. Ligation of the External Carotid Artery: With Remarks on the History of the Operation. PMID- 17856165 TI - IV. Report of Operation for Removal of Colossal Cystic Tumor of Lower Jaw. PMID- 17856166 TI - I. Abdominal Section for the Treatment of Intra-Peritoneal Injury. PMID- 17856167 TI - II. On Contagion Through the Use of Ether-Inhalers. PMID- 17856168 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856169 TI - I. Notes on Plastic Surgery. PMID- 17856170 TI - I. The Management and Treatment of Umbilical Herniae. PMID- 17856171 TI - II. On the Treatment of Old Dislocations of the Elbow. PMID- 17856172 TI - III. Practical Points in the Selection and Administration of Anaesthetics. PMID- 17856173 TI - I. On Stiffness and Tenderness of the Metacarpo-Phalangeal Joint of the Great Toe, and on "Hallux Flexus". PMID- 17856174 TI - II. Witzel on Injuries of Tendons, and their Treatment. PMID- 17856176 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856175 TI - III. A New Classification of Tumors in General, and of Tumors of the Testicle in Particular. PMID- 17856177 TI - I. The Osteogenic Factors in the Development and Repair of Bone. PMID- 17856178 TI - II. Aneurisms Treated by the Introduction of Catgut, or of Wire, with Electricity. PMID- 17856179 TI - III. Exsection of the Knee-Joint for Tuberculosis. PMID- 17856180 TI - IV. Case of Recovery from Stab-wound of Abdomen, with Wound of Colic Artery, and Large, Long Continued and Filth Infected Bowel-Protrusion. PMID- 17856181 TI - I. Ether or Chloroform-Which? PMID- 17856182 TI - II. On the Suture of Nerves. PMID- 17856183 TI - III. Heath on Certain Diseases of the Jaws. PMID- 17856184 TI - IV. Certain Points Relating to Syphilis. PMID- 17856185 TI - I. A Review of Some Facts Connected with Gunshot Wounds of the Abdomen, and Practical Deductions Therefrom. PMID- 17856186 TI - II. The Osteogenic Factors in the Development and Repair of Bone (concluded). PMID- 17856188 TI - I. Recent Contributions on the Subject of Tumors. PMID- 17856187 TI - III. Fracture and Dislocation of the Astragalus. PMID- 17856189 TI - II. Ollier on Simplification of the Post-Operative Treatment of Resections of the Knee-Joint. PMID- 17856191 TI - I. A New Surgical Operation for the Treatment of Cancer of the Stomach. PMID- 17856190 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856192 TI - II. Some Abnormal Conditions Which Complicate Colotomy. PMID- 17856193 TI - III. Malignant Tumor of the Upper Jaw. PMID- 17856194 TI - IV. Case of Chronic Cerebral Abscess. PMID- 17856195 TI - I. The Treatment of Scoliosis by Massage. PMID- 17856196 TI - II. Koehl on the Causes of the Difficulties in Dispensing with the Tube in Some Cases of Tracheotomy for Diphtheria. PMID- 17856197 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856198 TI - An Experimental Contribution to Intestinal Surgery with Special Reference to the Treatment of Intestinal Obstruction. PMID- 17856199 TI - The Relations of the Pelvic Peritoneum as shown by Frozen Sections, with Special Reference to Suprapubic Cystotomy. PMID- 17856200 TI - Simple and Compound Interphalangeal Dislocations of the fingers. PMID- 17856201 TI - Tetanus; its Nature and Origin. PMID- 17856202 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856203 TI - Erasion of the Knee Joint. PMID- 17856204 TI - On the Etiology and Essential Nature of Scoliosis. PMID- 17856205 TI - Recent Contributions to Rectal Surgery. PMID- 17856206 TI - The Disinfection of the Physician's Hands, with Observations on the Bacteriological Character of the Accumulations under the Finger Nails. PMID- 17856207 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856208 TI - Laparotomy for Acute Intestinal Obstruction, with a Report of a Successful Case by the Author. PMID- 17856209 TI - An Experimental Contribution to Intestinal Surgery, with Special Reference to the Treatment of Intestinal Obstruction (Continued). PMID- 17856210 TI - Inguino-properitoneal Hernia. PMID- 17856211 TI - An Experimental Contribution to Intestinal Surgery, with Special Reference to the Treatment of Intestinal Obstruction (Continued). PMID- 17856212 TI - OEsophagotomy for the Removal of an Ingested Foreign Body. PMID- 17856214 TI - On Cancer and Cancerous Diseases. PMID- 17856213 TI - A Case of Nephrorraphy for Fixation of a Floating Kidney. PMID- 17856215 TI - Gastro-enterostomy in Luecke's Clinic. PMID- 17856216 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856217 TI - The Modern Operative Treatment of Tubercular Joint Affections. PMID- 17856218 TI - Notes on Wry Neck and Its Treatment. PMID- 17856219 TI - Antiseptic Surgical Precautions of Special Importance to the General Practitioner. PMID- 17856220 TI - An Experimental Contribution to Intestinal Surgery, with Special Reference to the Treatment of Intestinal Obstruction (Continued). PMID- 17856221 TI - The Surgery of the Larynx. PMID- 17856222 TI - Material Organization of the Surgical Clinic at Paris. PMID- 17856223 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856224 TI - The Details of Ovariotomy. PMID- 17856225 TI - The Results of Laparotomy for Acute Intestinal Obstruction. PMID- 17856226 TI - Abdominal Section in Albany. PMID- 17856227 TI - An Experimental Contribution to Intestinal Surgery, with Special Reference to the Treatment of Intestinal Obstruction (Continued). PMID- 17856228 TI - The Surgical Treatment of Acute Intestinal Obstruction. PMID- 17856230 TI - On a Case of Subcranial Haemorrhage treated by Secondary Trephining. PMID- 17856229 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856232 TI - An Experimental Contribution to Intestinal Surgery, with Special Reference to the Treatment of Intestinal Obstruction (Concluded). PMID- 17856231 TI - Some Points in Incarcerated Hernia. PMID- 17856233 TI - The Ultimate Results in a Case of Exsection of the Head and Upper Third of the Humerus. PMID- 17856234 TI - The Etiology of the Ununited Fracture. PMID- 17856235 TI - A Model Operating Theatre and its Fittings. PMID- 17856236 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856238 TI - Laparotomy for Perforative Inflammation of the Vermiform Appendix. PMID- 17856237 TI - A Method of Wiring Fractures of the Patella. PMID- 17856239 TI - The French Congress of Surgery and the Radical Cure of Hernia. PMID- 17856240 TI - Asepsis in Antiseptic Dressing. PMID- 17856241 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856243 TI - Some Points of Practical Importance in the Operative Treatment of Rodent Ulcer. PMID- 17856242 TI - The Radical Cure of Hernia. PMID- 17856244 TI - The Padded Board Stretcher in the Treatment of Hip Disease and Various Traumata. PMID- 17856245 TI - Case of Sarcoma of the Scalp. PMID- 17856246 TI - On the Dystrophies Observed after Resections. PMID- 17856247 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856248 TI - Laparotomy for Gunshot Wound of Stomach and Liver. PMID- 17856249 TI - On Forming a new Acetabulum in certain Resections of the Hip-Joint. PMID- 17856250 TI - The Treatment of Urethral Stricture by Wheelhouse's Method. PMID- 17856251 TI - Case of Supracoracoid Dislocation of the Shoulder. PMID- 17856253 TI - Some Points in the Technique of the Treatment of Fracture of the Patella by Suture. PMID- 17856252 TI - Case of Dislocation of Inferior Maxilla left unreduced for Eighty Days. PMID- 17856254 TI - Senn on the Diagnosis of Gastro-Intestinal Perforation by the Rectal Insufflation of Hydrogen Gas. PMID- 17856256 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856255 TI - The Cure of Varicocele. PMID- 17856257 TI - On Traumatic Subdural Abscess of the Brain. PMID- 17856258 TI - Extensive Thoracotomy for Sarcoma of Chest Wall. PMID- 17856259 TI - Successful Laparotomy for Gunshot Wound of the Intestine. PMID- 17856260 TI - The Surgery of the Brain and Spinal Cord. PMID- 17856261 TI - Bergmann on the Surgical Treatment of Diseases of the Brain. PMID- 17856262 TI - Etiology of Fractures of the Skull. PMID- 17856263 TI - On Antiseptic Methods and other Points in the Practice of Volkmann. PMID- 17856264 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856266 TI - Ligature of the Subclavian Artery for Axillary Aneurism. PMID- 17856265 TI - Filaria Sanguinis Hominis; its Discovery in the United States and its Relation to Chylocele of the Tunica Vaginalis. PMID- 17856267 TI - Excision of the Tongue Followed by Death from Acute Miliary Tuberculosis. PMID- 17856268 TI - Operation for Strangulated Hernia Followed by Laparotomy for Intestinal Obstruction. PMID- 17856269 TI - Splenectomy for Leukaemic Enlargement. PMID- 17856270 TI - Note on Electrolysis for Uterine Fibroma. PMID- 17856271 TI - Note on a New Treatment of Dermoid Cysts of the Neck. PMID- 17856272 TI - The Diagnosis and Treatment of Pancreatic Cysts. PMID- 17856273 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856274 TI - Tuberculosis of the Sacro-Iliac Joint. PMID- 17856275 TI - Amputation of the Entire Upper Extremity in the Contiguity of the Trunk by Berger's Method. PMID- 17856276 TI - "Plastic" Amputation of the Foot. PMID- 17856277 TI - Case of Removal of Both Testicles for Recurrent Carcinoma of the Epididymis. PMID- 17856279 TI - The Treatment of Simple Fractures around and Penetrating into the Joints. PMID- 17856278 TI - The Arraignment of Catgut; The Desirability of Simplicity of Methods in Obtaining Certain Asepsis in Surgical Work. PMID- 17856280 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856281 TI - The Operative Treatment of the Hypertrophied Prostate. PMID- 17856282 TI - A Contribution to Cerebral Surgery. PMID- 17856283 TI - Tuberculosis of the Sacro-Iliac Joint. (Continued). PMID- 17856284 TI - On the Functional Prognosis of Tendon Suture. PMID- 17856285 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856286 TI - A Report on the Treatment of Club-Foot by Means of the Thomas Wrench. PMID- 17856287 TI - Separation of the Lower Epiphysis of the Femur. PMID- 17856288 TI - A Case of Exostosis Bursata. PMID- 17856289 TI - Tuberculosis of the Sacro-Iliac Joint. (Concluded). PMID- 17856290 TI - The Prognosis and Statistics of Operations for Carcinoma of the Rectum. PMID- 17856292 TI - Gastrostomy, with a Report of a Successful Case. PMID- 17856291 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856293 TI - A Report of Sixteen Cases of Laparotomy. PMID- 17856294 TI - Contribution to the Surgery of Cerebral Tumors. PMID- 17856295 TI - The Transplantation of Large Strips of Skin. PMID- 17856296 TI - Tracheotomy, with Ulceration of the Tube through Trachae into the Innominate Artery and Death. PMID- 17856297 TI - The Present Status of the Iodoform Question. PMID- 17856299 TI - The Etiology, Pathology and Operative Treatment of Rachitic Deformity. PMID- 17856298 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856300 TI - A Case of Spontaneous Fracture of a Vesical Calculus. PMID- 17856302 TI - Backward Diclocation of the Fingers upon the Metacarpus. PMID- 17856301 TI - Mammillaplasty. PMID- 17856304 TI - Skin Grafting According to Thiersch. PMID- 17856303 TI - Recent Contributions to Pulmonary Surgery. PMID- 17856305 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856306 TI - Hernia of the Pleura into the Neck. PMID- 17856307 TI - Simultaneous Ligature of the Common Carotid and Subclavian for Aneurism of Ascending Aorta. PMID- 17856308 TI - A Hitherto Undescribed Anomaly of the Lingual Artery. PMID- 17856309 TI - Injuries of the Heart. PMID- 17856310 TI - The Treatmen[ill] of Cerebral Abscess. PMID- 17856311 TI - Cancers of the Larynx. PMID- 17856312 TI - Electrolysis in Prostatic Enlargement. PMID- 17856313 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856314 TI - Subluxation of the Head of the Radius in Children. PMID- 17856315 TI - Two Cases of Spinal Surgery. PMID- 17856316 TI - Is Resection of the Knee-Joint Justifiable in Children? PMID- 17856317 TI - The Treatment of Gangrenous Hernia and Artificial Anus. PMID- 17856318 TI - The Dangers and Efficiency of the Modern Treatment of Wounds. PMID- 17856319 TI - INDEX OF SURGICAL PROGRESS. PMID- 17856320 TI - PRIMARY CARCINOMA OF THE LUNG: REPORT OF A CASE OF PRIMARY CARCINOMA OF THE UPPER LOBE OF THE LEFT LUNG, TREATED SUCCESSFULLY BY LOBECTOMY, AND SUBSEQUENT THORACOPLASTY. PMID- 17856321 TI - THE STUDY OF THE MORPHOLOGY OF THE WHITE CORPUSCLES OF THE BLOOD IN THE PROGNOSIS OF OPERATIONS. PMID- 17856322 TI - REMOVAL OF A BULLET FROM THE POSTERIOR WALL OF THE LEFT VENTRICLE OF THE HEART. PMID- 17856323 TI - ACUTE EMPYEMA IN CHILDREN. PMID- 17856324 TI - CONTRIBUTION TO THE DIAGNOSIS AND TREATMENT OF HYDATID CYSTS OF THE LUNG. PMID- 17856325 TI - INTESTINAL OBSTRUCTION: ANALYSIS OF 505 CASES FROM THE RECORDS OF COOK COUNTY HOSPITAL, CHICAGO, ILLINOIS. PMID- 17856326 TI - ACUTE INTESTINAL OBSTRUCTION: A COMPARATIVE STUDY OF 511 CASES, WITH SPECIAL REFERENCE TO THE LOWERED MORTALITY ACHIEVED BY MODERN METHODS OF THERAPY. PMID- 17856327 TI - PERISTALSIS AND PERITONITIS. PMID- 17856328 TI - GASTRODUODENAL RESECTION AS A SYSTEMATIC TREATMENT OF DUODENAL ULCER. PMID- 17856329 TI - PYLOROPLASTY: ITS PLACE IN THE TREATMENT OF PEPTIC ULCER. PMID- 17856330 TI - THE USE OF FASCIAL AND TENDON GRAFTS IN CERTAIN FRACTURES AND DISLOCATIONS. PMID- 17856332 TI - THE RADICAL SURGERY OF CANCER OF THE PANCREAS. PMID- 17856331 TI - APPENDICITIS. PMID- 17856333 TI - PANCREATIC CANCER AND ITS TREATMENT BY IMPLANTED RADIUM. PMID- 17856334 TI - SURGERY IN SYRIA. PMID- 17856335 TI - RETROPERITONEAL CYSTS. PMID- 17856336 TI - PATELLA BIPARTITA. PMID- 17856337 TI - ANATOMICAL STUDY UPON THE SUPERIOR HYPOGASTRIC PLEXUS OF THE PRESACRAL NERVE FROM THE SURGICAL STANDPOINT. PMID- 17856338 TI - THE PROBLEM OF EXTRADURAL HAEMORRHAGE: A REPORT OF 14 CASES. PMID- 17856339 TI - INFLUENCE OF ELEVATIONS OF THE BASIS CRANII INTERNA UPON OPERATIVE APPROACH TO THE SELLA TURCICA. PMID- 17856340 TI - ALCOHOL INJECTIONS OF THE GASSERIAN GANGLION FOR TRIGEMINAL NEURALGIA. PMID- 17856341 TI - CONGENITAL FISTULAE OF THE BODY OF THE TONGUE. PMID- 17856342 TI - VENOUS OBSTRUCTION IN THE UPPER MEDIASTINUM. PMID- 17856343 TI - TRAUMATIC ANEURISM OF THE SUBCLAVIAN ARTERY. PMID- 17856344 TI - Operability of Brain Tumors. PMID- 17856346 TI - Myositis Ossificans (Circumscripta) in the Ligamentum Nuchae. PMID- 17856345 TI - Physiological Considerations Related to the Infusion Treatment of Shock. PMID- 17856347 TI - Eye Complications in Exophthalmic Goitre: Cataracts and Exophthalmos. PMID- 17856348 TI - Traumatic Subdural Haemorrhage: Surgical Removal of Clot; Recovery. PMID- 17856350 TI - Liver Deaths (So-called): Rapid High Temperature Deaths. PMID- 17856349 TI - Subtotal Bilateral Adrenalectomy for Hyperadrenalism (Essential Hypertension). PMID- 17856351 TI - Malignant Tumors of the Large Intestine: Pathological Aspects of 210 Cases Coming to Necropsy. PMID- 17856352 TI - Deformities Resulting from Unilateral Surgical Trauma to the Epiphyses. PMID- 17856353 TI - Overpull During the Treatment of Fractures. PMID- 17856354 TI - Arthrotomy of the Knee-Joint: A Statistical Study of Two Hundred Fifty Cases. PMID- 17856355 TI - Recurrent Subluxation of the Ankle-Joint. PMID- 17856356 TI - Subcutaneous Rupture of the Tendon of the Tibialis Anticus. PMID- 17856357 TI - Transactions of the New York Surgical Society-Stated Meeting held January 10, 1934. PMID- 17856358 TI - Transactions of the New York Surgical Society-Stated Meeting held January 24, 1934. PMID- 17856359 TI - Osteochondroma of Chest Wall. PMID- 17856360 TI - Sarcoma of the Breast: With a Report of Sixty Cases. PMID- 17856362 TI - Cancer of the Kidney: Squamous-Cell Carcinoma of the Renal Pelvis with Special Reference to Etiology. PMID- 17856361 TI - The Treatment of Acute Traumatic Hemothorax. PMID- 17856363 TI - Congenital Urinary Anomalies: An Evaluation of the Associated Obstructive Syndrome with Report of 6 Cases. PMID- 17856365 TI - Tumors of the Lung, Secondary to Kidney Tumors. PMID- 17856364 TI - Advantages of Pre-operative X-ray in Kidney Tumor in Children. PMID- 17856366 TI - Carcinoma of the Penis: With Report of 37 Cases. PMID- 17856367 TI - Inflammatory Strictures of the Rectum and Their Relation to Lymphogranuloma Inguinale. PMID- 17856368 TI - Carcinoma of the Rectum: the Question of Operability. PMID- 17856369 TI - Procedures in Cleft Palate Surgery: Experiences with the Veau and Dorrance Technic. PMID- 17856370 TI - Osteopetrosis. PMID- 17856372 TI - Malignant Tumors of the Greater Omentum. PMID- 17856371 TI - Splenectomy in Mother and Daughter for Familial Haemolytic Jaundice. PMID- 17856373 TI - Congenital Syphilitic Osteomyelitis of the Mandible: A Report of two Analogous Cases in Sisters. PMID- 17856374 TI - Anterior Dislocation of the Shoulder-joint by Abduction and Internal Rotation. PMID- 17856375 TI - Carotid-Jugular Anastomosis: Its Affect Upon the Systemic Blood-Pressure of the Dog. PMID- 17856376 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting held March 5, 1934. PMID- 17856377 TI - Brief Communications. PMID- 17856378 TI - ADDRESS OF THE PRESIDENT: THE DIVISION OF SURGERY INTO SPECIALTIES. PMID- 17856380 TI - TOTAL THYROIDECTOMY FOR ANGINA PECTORIS. PMID- 17856379 TI - TOTAL ABLATION OF THE THYROID FOR ANGINA PECTORIS AND CONGESTIVE HEART FAILURE: RESULTS OF EIGHTEEN MONTHS' EXPERIENCE. PMID- 17856381 TI - THE OPERATIVE TREATMENT OF HYPERPARATHYROIDISM. PMID- 17856383 TI - DIABETES AND HYPERTHYROIDISM. PMID- 17856382 TI - TRANSPLANTATION OF LIVING GRAFTS OF THYROID AND PARATHYROID GLANDS. PMID- 17856384 TI - THE PRINCIPLES OF AND RESULTS AFTER AMPUTATION FOR DIABETIC GANGRENE. PMID- 17856385 TI - THE RELATION OF THE HYPOPHYSIS, HYPOTHALAMUS, AND THE AUTONOMIC NERVOUS SYSTEM TO CARBOHYDRATE METABOLISM. PMID- 17856386 TI - INDICATIONS AND CONTRA-INDICATIONS FOR DENERVATION OF THE ADRENAL GLANDS. PMID- 17856387 TI - THE SUPRARENAL CORTICAL SYNDROME WITH PRESENTATION OF TEN CASES. PMID- 17856388 TI - TRANSPLANTATION OF THE ADRENAL CORTEX FOR ADDISON'S DISEASE. PMID- 17856389 TI - A CONSIDERATION OF POSSIBLE TOXIC AND NERVOUS FACTORS IN THE PRODUCTION OF TRAUMATIC SHOCK. PMID- 17856391 TI - SHOCK WITH PARTICULAR REFERENCE TO THAT DUE TO HAEMORRHAGE AND TRAUMA TO MUSCLES. PMID- 17856390 TI - PRIMARY SHOCK. PMID- 17856392 TI - THE EFFECT OF ADRENAL CORTICAL EXTRACT IN CONTROLLING SHOCK FOLLOWING THE INJECTION OF AQUEOUS EXTRACTS OF CLOSED INTESTINAL LOOPS. PMID- 17856393 TI - THE CONSERVATIVE TREATMENT OF ARTERIOSCLEROTIC PERIPHERAL VASCULAR DISEASES: PASSIVE VASCULAR EXERCISES (PAVAEX THERAPY). PMID- 17856394 TI - SIMULTANEOUS VEIN LIGATION: AN EXPERIMENTAL AND CLINICAL STUDY OF THERAPEUTIC VENOUS OCCLUSION. PMID- 17856395 TI - BILATERAL TRIGEMINAL NEURALGIA. PMID- 17856396 TI - GYNECOMASTIA, VIRGINAL HYPERTROPHY AND FIBROADENOMAS OF THE BREAST. PMID- 17856397 TI - THE TECHNIC OF TOTAL UNILATERAL PNEUMONECTOMY. PMID- 17856398 TI - ELEPHANTIASIS AND THE CLINICAL IMPLICATIONS OF ITS EXPERIMENTAL REPRODUCTION IN ANIMALS. PMID- 17856399 TI - DISPLACEMENTS IN FRACTURES OF THE NECK OF THE FEMUR. PMID- 17856401 TI - THERAPEUTIC PORTENT OF BIOLOGY OF CANCER. PMID- 17856400 TI - THE GENERAL QUESTION OF THE EMERGENCY TREATMENT OF FRACTURES. PMID- 17856403 TI - Transactions of the New York Surgical Society-Clinical Meeting held March 28, 1934. PMID- 17856402 TI - The Importance of Adequate Masking During Operation. PMID- 17856404 TI - Transactions of the New York Surgical Society-Stated Meeting held April 11, 1934. PMID- 17856405 TI - Max Ballin, M.D. 1869-1934. PMID- 17856406 TI - Burton James Lee 1874-1933. PMID- 17856407 TI - Frederic Newton Gisborne Starr, M.D. 1867-1934. PMID- 17856408 TI - Sir William Taylor, M.D. 1871-1933. PMID- 17856409 TI - The Old and the New in Prostatic Surgery. PMID- 17856410 TI - Uretero-Arachnoid (Ureterodural) Anastomosis: With Report of Three Cases. PMID- 17856411 TI - Treatment of Carcinoma of the Thyroid Gland. PMID- 17856412 TI - Thyroid Surgery as Affected by the Generalized Use of Iodized Salt in an Endemic Goitre Region-Preventive Surgery. PMID- 17856413 TI - The Pathology and Treatment of Bleeding Polypoid Tumors of the Large Bowel. PMID- 17856415 TI - Free Omental Grafts in Abdominal Operations. PMID- 17856414 TI - Tumors of the Small Intestine. PMID- 17856416 TI - Post-Operative Evisceration: With an Analysis of Forty-Four Cases. PMID- 17856417 TI - The Function of Peripheral Vasoconstriction. PMID- 17856418 TI - Primary Carcinoma of the Bartholin Gland. PMID- 17856419 TI - Fractures of the Skull: A Review and Summary of 30 Years Experience. PMID- 17856420 TI - Results of Operations on Painful Hips. PMID- 17856421 TI - Anterothoracic Oesophagoplasty for Impermeable Stricture of the Oesophagus. PMID- 17856423 TI - Observation on Chronic Empyema. PMID- 17856422 TI - The Treatment of Empyema. PMID- 17856424 TI - Putrid Empyema: Ruptured Putrid Abscess of the Lung. PMID- 17856425 TI - Diverticula of the Small Bowel. PMID- 17856426 TI - Polycystic Disease of the Kidney. PMID- 17856427 TI - Post-Operative Wound Complications. PMID- 17856428 TI - Abdominal-Wall Defects following Appendicectomy. PMID- 17856430 TI - Transactions of the New York Surgical Society-Stated Meeting held March 14, 1934. PMID- 17856429 TI - Transactions of the New York Surgical Society-Stated Meeting held February 28, 1934. PMID- 17856431 TI - PHYSIOLOGICAL ASPECTS OF DISEASES OF THE OPTIC NERVE. PMID- 17856432 TI - MOTOR AND SENSORY OVERLAP IN THE SPINAL ROOTS. PMID- 17856433 TI - INTRACRANIAL OPERATIONS IN THE SITTING POSITION. PMID- 17856434 TI - TUMORS ARISING FROM THE SENSORY ROOT OF THE TRIGEMINAL NERVE IN THE POSTERIOR FOSSA: PERINEURIAL FIBROBLASTOMA. PMID- 17856435 TI - BRAIN LESIONS AND DUODENAL ULCER: REPORT OF TWO CASES. PMID- 17856436 TI - THE MENINGIOMA AS A CAUSE OF EPILEPSY. PMID- 17856437 TI - THE OCCURRENCE OF FRANK HEMIANOPSIA: PERIMETRIC STUDIES OF 2,500 CASES. PMID- 17856439 TI - BRAIN ABSCESS: EXTERNAL RUPTURE OF "CAPSULE" WITH PERICAPSULAR BRAIN NECROSIS. PMID- 17856438 TI - THE FUNCTIONS AND STRUCTURE OF THE NEURAXIS IN REGARD TO VOLUNTARY AND REFLEX MOVEMENTS. PMID- 17856440 TI - DEFORMATION OF THE SELLA TURCICA BY TUMORS IN THE PITUITARY FOSSA. PMID- 17856442 TI - THE TREATMENT OF CAUSALGIA BY THORACIC SYMPATHETIC GANGLIONECTOMY. PMID- 17856441 TI - THE CUTANEOUS DISTRIBUTION OF THE TRIGEMINAL NERVE. PMID- 17856443 TI - THE SELECTION OF PITUITARY CASES FOR SURGERY. PMID- 17856445 TI - THE RONTGEN DIAGNOSTIC SIGNIFICANCE OF EROSION OF THE OPTIC CANALS IN THE STUDY OF INTRACRANIAL TUMORS. PMID- 17856444 TI - CHRONIC GENERALIZED FIBROMYOSITIS. PMID- 17856446 TI - GLOSSOPHARYNGEAL NEURALGIA. PMID- 17856447 TI - DILATATIONS OF THE CAVUM SEPTI PELLUCIDI AND CAVUM VERGAE. PMID- 17856448 TI - CEREBRAL OSTEOCHONDROMA OF DURAL ORIGIN. PMID- 17856449 TI - TRANSIENT HYPOTENSION AS A FACTOR IN CEREBRAL THROMBOSIS. PMID- 17856450 TI - ENCEPHALITIS LETHARGICA: WITH REPORT OF CASES. PMID- 17856451 TI - PSYCHOSIS FOLLOWING CATARACT OPERATIONS: REPORT OF THREE CASES. PMID- 17856452 TI - OCCLUSION OF THE CENTRAL ARTERY OF THE RETINA. PMID- 17856453 TI - THROMBO-ANGIITIS OBLITERANS IN WOMEN: REPORT OF TWO CASES. PMID- 17856454 TI - BILATERAL PARALYSIS OF THE FACIAL AND ABDUCENT NERVES AS REMOTE EFFECT OF TUMOR OF THE BRAIN. PMID- 17856455 TI - DECEREBRATE RIGIDITY IN CHILDREN. PMID- 17856456 TI - BENIGN CYSTS OF THE CEREBELLUM: WITH A REPORT OF TWO CASES. PMID- 17856457 TI - UNCLASSIFIED ORGANIC PSYCHOSIS. PMID- 17856458 TI - THE EFFECT OF LESIONS OF THE HYPOTHALAMUS UPON THE GASTRO-INTESTINAL TRACT AND HEART IN MONKEYS. PMID- 17856460 TI - DEAFNESS AS A PSYCHOLOGICAL ENTITY. PMID- 17856459 TI - APHASIA IN BRAIN TUMORS. PMID- 17856462 TI - OBSERVATIONS ON TOTAL PULMONARY LOBECTOMY AND PNEUMONECTOMY. PMID- 17856461 TI - PATHOLOGY OF ACUTE PURULENT MENINGITIS. PMID- 17856463 TI - SURGERY IN CHRONIC MIDDLE-EAR INFECTION. PMID- 17856464 TI - EXCISION OF PELVIC AUTONOMIC NERVES FOR THE RELIEF OF PAIN FROM ADVANCED PELVIC CARCINOMA. PMID- 17856465 TI - NEUROCYTOMA OF THE KIDNEY. PMID- 17856466 TI - HYPERTHYROIDISM ASSOCIATED WITH PREGNANCY. PMID- 17856467 TI - AFFECTIONS OF THE SPHENOPALATINE GANGLION. PMID- 17856468 TI - NON-SURGICAL CAUSES OF ACUTE ABDOMINAL PAIN. PMID- 17856470 TI - THE "PUSH-BACK OPERATION" IN CLEFT-PALATE SURGERY. PMID- 17856469 TI - POST-ENCEPHALITIC PERSONALITY DISORDERS: THEIR NATURE AND TREATMENT. PMID- 17856471 TI - MORTALITY IN SURGERY OF THE BILIARY TRACT: A COMPARISON OF TWO SIX-YEAR PERIODS. PMID- 17856472 TI - PILONIDAL CYSTS: TREATMENT BY EXCISION AND PRIMARY SUTURE IN AMBULATORY PATIENTS. PMID- 17856473 TI - CARDIAC IMPROVEMENT FOLLOWING GALL-BLADDER SURGERY: ELECTROCARDIOGRAPHIC EVIDENCE IN CASES WITH ASSOCIATED MYOCARDIAL DISEASE. PMID- 17856474 TI - HAEMORRHAGE IN RELATION TO SHOCK: EXPERIMENTAL EFFECT OF INTRAVENOUS INJECTIONS OF SALINE, GUM ACACIA, AND BLOOD ON THE RATE OF ADRENAL SECRETION RESULTING FROM HAEMORRHAGE. PMID- 17856475 TI - LINGUAL SPASM. PMID- 17856476 TI - EFFECT OF SUPERIOR LARYNGEAL NERVES ON TRACHEAL MUCUS: AN EXPERIMENTAL STUDY ON THE RELATIONSHIP. PMID- 17856477 TI - ACTION OF GLUCOSE ON EMPTYING OF STOMACH: EFFECT OF VARYING CONCENTRATIONS IN BOTH NORMAL STOMACHS AND AFTER VARIOUS GASTRIC OPERATIONS. PMID- 17856478 TI - DOCTOR WILLIAM HUNTER OF NEWPORT. PMID- 17856480 TI - THE GASTRIC ULCER-CANCER PROBLEM. PMID- 17856479 TI - AMNIOTIC FLUID: A CLINICAL STUDY. PMID- 17856481 TI - THE USE OF PERITONEUM IN THE REPAIR OF INGUINAL HERNIA. PMID- 17856482 TI - INTESTINAL ULCERATION FOLLOWING ADRENAL DAMAGE: EXPERIMENTAL OBSERVATIONS. PMID- 17856483 TI - RECURRENT EMPYEMA THORACIS. PMID- 17856484 TI - OPHTHALMIC SYMPTOMS IN BRAIN ABSCESS. PMID- 17856485 TI - SUBCLAVIAN ANEURISM: WITH REPORT OF A CASE. PMID- 17856486 TI - THE SOCIAL AND ECONOMIC IMPLICATIONS OF THREE COMMON SOUTHERN DISEASES. PMID- 17856487 TI - SELECTIVE THORACOPLASTY IN THE TREATMENT OF PULMONARY TUBERCULOSIS. PMID- 17856488 TI - OBSCURE PSEUDOMEMBRANOUS TRIGONITIS: TRIGONITIS AREATA ALBA. PMID- 17856489 TI - THE RELATIONSHIP OF CHOLECYSTITIS AND CHOLECYSTECTOMY TO DILATATION OF THE CHOLEDOCHUS. PMID- 17856490 TI - THE STATE OF UNILATERAL ANURIA IN BLADDER MALIGNANCY. PMID- 17856492 TI - PRIMARY CARCINOMA OF THE LIVER WITH SPONTANEOUS RUPTURE AND LETHAL HAEMORRHAGE. PMID- 17856491 TI - THE HAEMORRHAGIC TENDENCY IN OBSTRUCTIVE JAUNDICE. PMID- 17856493 TI - ACUTE EMPYEMA IN CHILDREN: REPORT OF 310 CASES. PMID- 17856494 TI - THE FORMATION OF GALL-STONES. PMID- 17856495 TI - COMPLICATED DISLOCATIONS. PMID- 17856496 TI - THE RELATION OF OPHTHALMOLOGY AND NEUROSURGERY: SOME REMINISCENCES. PMID- 17856498 TI - THE SURGICAL MANAGEMENT OF BRAIN ABSCESS. PMID- 17856497 TI - ESSENTIAL HAEMATURIA: A CLINICAL AND PATHOLOGIC STUDY. PMID- 17856499 TI - THE TREATMENT OF ACUTE AND CHRONIC CASES OF CEREBRAL TRAUMA, BY METHODS OF DEHYDRATION. PMID- 17856500 TI - EDITORIAL. PMID- 17856501 TI - EULOGY OF LEWIS STEPHEN PILCHER, M.D., LL.D. PMID- 17856502 TI - THE PROBLEM OF DRAINING THE ABDOMINAL CAVITY IN CASES OF GENERAL PERITONITIS. PMID- 17856503 TI - THE SURGICAL MANAGEMENT OF CHRONIC SUBDURAL HEMATOMA. PMID- 17856504 TI - SPINAL ANALGESIA: A REPORT OF 1,500 CASES. PMID- 17856505 TI - THE USE AND ABUSE OF SPINAL ANAESTHESIA. PMID- 17856506 TI - JEJUNOSTOMY WITH JEJUNAL ALIMENTATION. PMID- 17856507 TI - LEIOMYOMA OF THE SMALL INTESTINE. PMID- 17856508 TI - SUBMUCOUS LIPOMAS OF THE INTESTINAL TRACT, AS A CAUSE OF INTESTINAL OBSTRUCTION. PMID- 17856509 TI - ACUTE TUBERCULOUS APPENDICITIS. PMID- 17856510 TI - CYSTINE NEPHROLITHIASIS: REPORT OF TWO CASES. PMID- 17856511 TI - TREATMENT OF RECURRENT INCISIONAL HERNIA BY FLAPS OF THE ANTERIOR SHEATH OF THE RECTUS. PMID- 17856512 TI - FIBROSARCOMA OF THE EXTREMITIES. PMID- 17856514 TI - COMPRESSED FRACTURES OF THE VERTEBRAE. PMID- 17856513 TI - ARTERIOGRAPHY IN GANGRENE OF THE EXTREMITIES BY THE USE OF THORIUM DIOXIDE (Stabilized): A STUDY BASED ON TWENTY-SEVEN CASES. PMID- 17856515 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY AND THE NEW YORK SURGICAL SOCIETY: Joint Meeting Held February 14, 1934. PMID- 17856517 TI - BRIEF COMMUNICATIONS. PMID- 17856516 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY: Stated Meeting Held April 25, 1934. PMID- 17856518 TI - THE PALATINE ACCESS TO THE GANGLION SPHENOPALATINUM AND TO THE SECOND BRANCH OF THE TRIFACIAL NERVE. PMID- 17856519 TI - MEDIASTINAL GANGLIONEUROMA. PMID- 17856520 TI - NEUROFIBROMA OF THE HYPOGLOSSAL NERVE. PMID- 17856521 TI - BLEEDING MALIGNANT POLYPOID LESIONS IN THE CARDIA OF THE STOMACH: ASSOCIATED WITH SEVERE ANEMIA: REPORT OF THREE CASES. PMID- 17856522 TI - PEPTIC ULCERS INVOLVING THE GREATER CURVATURE OF THE STOMACH. PMID- 17856523 TI - MASSIVE HEMORRHAGE IN PEPTIC ULCER: REPORT OF 87 CASES. PMID- 17856524 TI - CARCINOMAS OF THE LARGE BOWEL. (Part I.): THE COLON. PMID- 17856526 TI - OMENTOPEXY IN PORTAL CIRRHOSIS OF THE LIVER WITH ASCITES: A REVIEW OF TWENTY THREE CASES. PMID- 17856525 TI - INTRAPERITONEAL VACCINATION IN SURGERY OF THE COLON. PMID- 17856527 TI - ACUTE CHOLECYSTITIS. PMID- 17856528 TI - CHOLEDOCHUS CYST WITH A DOUBLE COMMON BILE DUCT. PMID- 17856529 TI - CHANGES IN THE BILIARY SYSTEM AFTER CHOLECYSTECTOMY: THE CAUSES OF RECURRENCE OF GALLBLADDER SYMPTOMS. PMID- 17856530 TI - SKIN GRAFTING. PMID- 17856532 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. 2, 1934: Stated Meeting Held April. PMID- 17856531 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. 9, 1934: Stated Meeting Held May. PMID- 17856533 TI - BRIEF COMMUNICATIONS. PMID- 17856534 TI - PARATHYROIDECTOMY FOR RAYNAUD'S DISEASE AND SCLERODERMA: A PRELIMINARY REPORT. PMID- 17856535 TI - MECKEL'S DIVERTICULUM. PMID- 17856536 TI - CARCINOMA OF THE LARGE BOWEL (PART II.): THE RECTUM. PMID- 17856537 TI - SURGICAL TREATMENT OF RECTAL PROLAPSE: A NEW OPERATION FOR ITS RELIEF. PMID- 17856538 TI - OSTEOCHONDRITIS OF THE GROWTH CENTERS. PMID- 17856539 TI - FRACTURE OF THE EXTERNAL CONDYLE OF THE HUMERUS IN CHILDREN. PMID- 17856540 TI - AVULSION OF EPIPHYSIS OF ILIAC CREST. PMID- 17856541 TI - AN AMBULATORY METHOD OF TREATING FRACTURES OF THE PATELLA. PMID- 17856542 TI - ANKLE BONE BLOCK FOR PARALYTIC DROP FOOT: END-RESULTS OF EIGHTY-FIVE CASES, 1925 1932. PMID- 17856544 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. 10, 1934: Stated Meeting Held October. PMID- 17856543 TI - CYSTOSCOPY AND UROGRAPHY. PMID- 17856545 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. 29, 1934: Stated Meeting Held October. PMID- 17856546 TI - LYMPHOSARCOMA OF THE STOMACH: REPORT OF A CASE WITH A NINETEEN-YEAR SURGICAL CURE. PMID- 17856547 TI - THE ROLE OF PLASTIC SURGERY IN BURNS DUE TO ROENTGEN RAYS AND RADIUM. PMID- 17856548 TI - FRANKLIN H. MARTIN 1857-1935: A RETROSPECT AND AN APPRECIATION. PMID- 17856550 TI - MALIGNANCY OF THE GALLBLADDER. PMID- 17856549 TI - ZINC PEROXIDE IN THE TREATMENT OF MICROAEROPHILIC AND ANAEROBIC INFECTIONS: WITH SPECIAL REFERENCE TO A GROUP OF CHRONIC, ULCERATIVE, BURROWING, NON-GANGRENOUS LESIONS OF THE ABDOMINAL WALL APPARENTLY DUE TO A MICRO-AEROPHILIC HAEMOLYTIC STREPTOCOCCUS. PMID- 17856551 TI - CYSTIC DISEASE OF THE BREAST. PMID- 17856552 TI - BRACHIAL PLEXUS BLOCK ANAESTHESIA. PMID- 17856553 TI - LUGOL'S SOLUTION IN ACUTE SECONDARY PAROTITIS. PMID- 17856554 TI - THE TREATMENT OF SALIVARY FISTULA BY IRRADIATION. PMID- 17856555 TI - HYPERTHYROIDISM IN THE AGED. PMID- 17856556 TI - MALIGNANT NEOPLASM OF THE THYROID. PMID- 17856557 TI - END-RESULTS OF THYROID SURGERY. PMID- 17856558 TI - OPERABILITY OF CARCINOMA OF THE STOMACH. PMID- 17856559 TI - SARCOMA OF THE STOMACH: A REPORT OF NINE CASES. PMID- 17856560 TI - PRIMARY PERFORATED JEJUNAL ULCER. PMID- 17856561 TI - ACUTE INTESTINAL OBSTRUCTION. PMID- 17856562 TI - DIASTASIC PERFORATION OF THE NORMAL CECUM: RESULTING FROM OBSTRUCTION OF THE COLON. PMID- 17856564 TI - APPENDICES FOUND AS CONTENTS OF FEMORAL HERNIAE. PMID- 17856563 TI - HERNIORRHAPHY USING A LIVING FASCIAL FLAP. PMID- 17856565 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting Held May 7, 1934. PMID- 17856566 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Clinical Meeting November 28, 1934. PMID- 17856567 TI - BRIEF COMMUNICATIONS. PMID- 17856568 TI - MEMOIR: Frederick Shepard Dennis 1850-1934. PMID- 17856570 TI - SUBTOTAL PANCREATECTOMY FOR HYPERINSULINISM: OPERATIVE TECHNIC. PMID- 17856569 TI - ADENOMA OF ISLET CELLS WITH HYPERINSULINISM: A REVIEW. PMID- 17856571 TI - THE SURGICAL TREATMENT OF CHRONIC PANCREATITIS. PMID- 17856572 TI - THE SUPERIOR LARYNGEAL NERVE AND THE SUPERIOR POLE IN THYROIDECTOMIES. PMID- 17856573 TI - SURGICAL TREATMENT OF TOXIC GOITER. PMID- 17856575 TI - SURGICAL ASPECTS OF BLEEDING GASTRIC AND DUODENAL ULCER. PMID- 17856574 TI - TRAUMATIC INTRATHORACIC RUPTURE OF THE THORACIC DUCT WITH CHYLOTHORAX: REPORT OF A CASE WITH RECOVERY. PMID- 17856576 TI - SPONTANEOUS RUPTURE OF A NORMAL SPLEEN. PMID- 17856577 TI - GAS GANGRENE: A REVIEW OF SEVENTEEN CASES. PMID- 17856578 TI - CARCINOMA OF THE BLADDER. PMID- 17856579 TI - SURGERY OF BLADDER TUMORS. PMID- 17856580 TI - TOTAL CYSTECTOMY FOR CANCER OF THE BLADDER. PMID- 17856581 TI - DIATHERMY FOR CARCINOMA OF THE BLADDER. PMID- 17856582 TI - RADIUM TREATMENT OF CANCER OF THE BLADDER. PMID- 17856583 TI - TREATMENT OF BLADDER CANCER WITH EXTERNAL IRRADIATION. PMID- 17856584 TI - THE UPPER URINARY TRACT IN CARCINOMA OF THE BLADDER. PMID- 17856585 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17856586 TI - TRANSPLANTATION OF TOES FOR FINGERS. PMID- 17856587 TI - FRACTURES OF THE BODIES OF THE VERTEBRAE. PMID- 17856588 TI - ARTHROPLASTY OF THE HIP AND THE PRESERVATION OF ITS STABILITY. PMID- 17856589 TI - THE TRAUMATIC KNEE: STATISTICAL SURVEY OF ONE HUNDRED AND FORTY-SIX CASES. PMID- 17856590 TI - INTERNAL DERANGEMENTS OF THE KNEE. PMID- 17856591 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17856592 TI - GANGLIONECTOMY FOR HYPERHIDROSIS. PMID- 17856593 TI - SPLANCHNIC NERVE SECTION IN JUVENILE DIABETES: II. TECHNIC AND POSTOPERATIVE MANAGEMENT. PMID- 17856594 TI - INFECTIVE GRANULOMA OF STOMACH: PSEUDOCANCER. PMID- 17856595 TI - FIBROSARCOMA OF THE STOMACH. PMID- 17856596 TI - ACUTE AXIAL TORSION OF THE UTERUS. PMID- 17856597 TI - TORSION OF AN INTRA-ABDOMINAL TESTICLE. PMID- 17856598 TI - RUPTURED PYO-URACHUS COMPLICATED BY URETHRAL STRICTURE. PMID- 17856599 TI - POSTOPERATIVE PULMONARY ATELECTASIS: REPORT OF ELEVEN CASES. PMID- 17856601 TI - THE PATHOLOGY OF INTESTINAL CARCINOMA. PMID- 17856600 TI - PREDISPOSING FACTORS AND DIAGNOSIS OF RECTAL CANCER: A DISCUSSION OF ALLERGY. PMID- 17856602 TI - THE ONE STAGE ABDOMINOPERINEAL OPERATION FOR CARCINOMA OF THE RECTUM. PMID- 17856603 TI - TWO STAGE OPERATION FOR RECTAL CANCER. PMID- 17856604 TI - GOLD RADON SEEDS IN RECTAL CANCER. PMID- 17856605 TI - EXTERNAL IRRADIATION IN RECTAL CANCER. PMID- 17856607 TI - FRACTURE OF THE ANTERIOR INFERIOR SPINE OF THE ILEUM: SPRINTER'S FRACTURE. PMID- 17856606 TI - ANAL ANATOMY WITH REFERENCE TO THE WHITE LINE OF HILTON AND THE PECTEN OF STROUD. PMID- 17856608 TI - MANAGEMENT OF DEPRESSED FRACTURES OF THE SKULL AND OLD SKULL DEFECTS. PMID- 17856609 TI - THE TREATMENT OF BRONCHIAL ASTHMA BY DORSAL SYMPATHECTOMY: DIRECT AND INDIRECT. PMID- 17856610 TI - MESENTERIC VASCULAR OCCLUSION. PMID- 17856611 TI - PERFORATED ULCERS OF THE DUODENUM: A STUDY OF FORTY-ONE CASES. PMID- 17856612 TI - ENLARGEMENT OF THE GALLBLADDER. PMID- 17856614 TI - THE SEQUELAE AFTER CHOLECYSTOSTOMY: WITH SPECIAL REFERENCE TO CHOLELITHIASIS. PMID- 17856613 TI - THE RELATION OF CHOLECYSTITIS TO PATHOLOGIC CHANGES IN THE LIVER. PMID- 17856615 TI - HISTOLOGIC GRADING OF MAMMARY CARCINOMA: IN A SERIES FOLLOWED FOR TEN YEARS. PMID- 17856616 TI - EARLY DIAGNOSIS OF CANCER OF THE BREAST. PMID- 17856617 TI - BIOPSY IN BREAST LESIONS: IN RELATION TO DIAGNOSIS, TREATMENT AND PROGNOSIS. PMID- 17856618 TI - CLASSIFICATION OF MAMMARY CANCER. PMID- 17856619 TI - SURGICAL PRINCIPLES IN CANCER OF THE BREAST. PMID- 17856620 TI - THE VALUE OF PREOPERATIVE IRRADIATION IN BREAST CANCER: STUDIES ON EIGHTY-ONE OPERABLE CASES. PMID- 17856621 TI - BONE GROWTH AND REPAIR. PMID- 17856623 TI - A MODIFICATION OF THE OPERATION FOR SPINAL FUSION. PMID- 17856622 TI - THE TREATMENT OF TUBERCULOSIS OF THE SPINE IN YOUNG CHILDREN. PMID- 17856624 TI - LIGATION OF VARICOSE VEINS: AMBULATORY TREATMENT PRELIMINARY TO SCLEROSING INJECTIONS. PMID- 17856625 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17856626 TI - NONOPERATIVE TREATMENT OF PERIPHERAL VASCULAR DISEASES. PMID- 17856627 TI - ARTERIAL SPASM IN THE EXTREMITIES. PMID- 17856629 TI - RELATIONSHIP OF THE PARATHYROID GLAND TO CALCIUM METABOLISM. PMID- 17856628 TI - INDICATIONS FOR AMPUTATION IN PROGRESSIVE ARTERIAL OBLITERATION OF THE LOWER EXTREMITIES. PMID- 17856630 TI - THE OBER OPERATION FOR SCIATICA. PMID- 17856631 TI - OBSTRUCTIVE JAUNDICE. PMID- 17856632 TI - SUBCUTANEOUS PERFORATION OF THE JEJUNUM. PMID- 17856633 TI - THE INDICATIONS FOR GASTROSTOMY AND JEJUNOSTOMY. PMID- 17856634 TI - TORSION AND VOLVULUS OF THE STOMACH WITH DIAPHRAGMATIC HERNIA. PMID- 17856635 TI - INVISCERATION. PMID- 17856636 TI - PNEUMOCOCCUS PERITONITIS: AN ANALYSIS OF SEVEN CASES. PMID- 17856637 TI - PENETRATING WOUNDS OF THE ABDOMEN. PMID- 17856638 TI - REGIONAL (TERMINAL) ILEITIS. PMID- 17856639 TI - RADIUM BURNS OF THE RECTUM. PMID- 17856640 TI - THERMAL BURNS. PMID- 17856641 TI - THE BLEEDING VOLUME IN SEVERE BURNS. PMID- 17856642 TI - PILONIDAL CYSTS AND SINUSES. PMID- 17856643 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17856644 TI - ADDRESS OF THE PRESIDENT: HIGHER DEGREES IN THE PROFESSION OF SURGERY. PMID- 17856645 TI - UNDERGRADUATE TEACHING OF SURGERY. PMID- 17856646 TI - GRADUATE TEACHING OF SURGERY IN UNIVERSITY CLINICS. PMID- 17856648 TI - HIPPOCRATIC SURGERY. PMID- 17856647 TI - OPPORTUNITIES FOR GRADUATE TEACHING OF SURGERY IN LARGER QUALIFIED HOSPITALS. PMID- 17856649 TI - THE PRINCIPLES OF PHYSIOLOGY INVOLVED IN THE MANAGEMENT OF INCREASED INTRACRANIAL PRESSURE. PMID- 17856650 TI - THE DIAGNOSTIC VALUE OF PHOSPHATOSE DETERMINATIONS IN THE STUDY OF BONE TUMORS. PMID- 17856651 TI - SOME PHYSIOLOGIC PRINCIPLES INVOLVED IN THE SURGICAL TREATMENT OF GASTRIC AND DUODENAL ULCER. PMID- 17856652 TI - FACTORS GOVERNING THE RESULTS OF SURGICAL TREATMENT OF DUODENAL ULCER. PMID- 17856653 TI - THE POSSIBILITY OF MALIGNANCY AS IT AFFECTS THE TREATMENT OF CHRONIC GASTRIC ULCER. PMID- 17856654 TI - ACUTE ILEUS: COMPARISON OF TOXICITY OF OBSTRUCTED AND NON-OBSTRUCTED INTESTINAL CONTENTS. PMID- 17856655 TI - CIRCULATORY DISTURBANCES CAUSED BY INTESTINAL OBSTRUCTION. PMID- 17856656 TI - MESENTERIC VASCULAR OCCLUSION. PMID- 17856657 TI - RESULTS OF SPLENECTOMY IN CHILDHOOD. PMID- 17856658 TI - IDIOPATHIC ULCERATIVE COLITIS: A REVIEW OF 149 CASES WITH PARTICULAR REFERENCE TO THE VALUE OF, AND INDICATIONS FOR SURGICAL TREATMENT. PMID- 17856659 TI - REGIONAL ILEITIS. PMID- 17856660 TI - NON-SPECIFIC GRANULOMA OF ILEOCECAL REGION. PMID- 17856662 TI - PEPTIC ULCER AND DISEASES OF THE BILIARY TRACT IN THE SOUTHERN NEGRO: THE INFLUENCE OF DIET. PMID- 17856661 TI - COLECTOMY FOR ADENOMATOSIS AND PSEUDOPOLYPOSIS: A REPORT OF FIVE ADDITIONAL CASES. PMID- 17856663 TI - LIVER RESECTION: CASE REPORT AND ADVANTAGES OF RADIOCUTTING. PMID- 17856665 TI - STENOSIS OF THE BILE DUCTS BY CONTIGUOUS CICATRICIAL TISSUE. PMID- 17856664 TI - CONGENITAL OBSTRUCTION OF THE BILE DUCTS. PMID- 17856666 TI - TREATMENT OF CARCINOMA OF THE AMPULLA OF VATER. PMID- 17856667 TI - A TECHNIC FOR HEPATICODUODENOSTOMY. PMID- 17856668 TI - THE OPERATIVE REPAIR OF SLIDING HERNIA OF THE SIGMOID. PMID- 17856669 TI - MEMOIR: LEWIS STEPHEN PILCHER 1845-1934. PMID- 17856670 TI - THE DEVELOPMENT OF A NEW BLOOD SUPPLY TO THE HEART BY OPERATION. PMID- 17856671 TI - TRAUMATIC CARCINOMA OF THE BREAST. PMID- 17856673 TI - OVARIAN TUMORS WITH ENDOCRINE SIGNIFICANCE. PMID- 17856672 TI - SURGICAL SIGNIFICANCE OF ENDOMETRIOSIS. PMID- 17856674 TI - CHOICE OF METHODS OF DIVERTING THE URINARY STREAM ABOVE THE LEVEL OF THE BLADDER. PMID- 17856675 TI - DIVISION OF THE SPERMATIC CORD AS AN AID IN OPERATING ON SELECTED TYPES OF INGUINAL HERNIA. PMID- 17856676 TI - THE UNDESCENDED TESTIS: ITS FATE AFTER SATISFACTORY SCROTAL ANCHORAGE. PMID- 17856677 TI - SUBACUTE STREPTOCOCCUS VIRIDANS SEPTICEMIA: CURED BY THE EXCISION OF AN ARTERIOVENOUS ANEURYSM OF THE EXTERNAL ILIAC ARTERY AND VEIN. PMID- 17856678 TI - THE TREATMENT OF CAROTID CAVERNOUS ARTERIOVENOUS ANEURYSMS. PMID- 17856679 TI - INFLUENCE OF URINARY BLADDER TRANSPLANTS ON HYALINE CARTILAGE. PMID- 17856680 TI - THE CLINICAL SIGNIFICANCE OF EXPERIMENTAL STUDIES IN WOUND HEALING. PMID- 17856681 TI - A STUDY OF DEHYDRATION IN HUMANS. PMID- 17856682 TI - JEJUNAL ULCER. PMID- 17856683 TI - CARCINOMA OF THE JEJUNUM: REPORT OF THREE CASES. PMID- 17856684 TI - THE SURGICAL DIABETIC: A FIVE YEAR SURVEY. PMID- 17856685 TI - INTESTINAL OBSTRUCTION: EVALUATION OF THE ROENTGEN DIAGNOSIS. PMID- 17856686 TI - THE PROBLEM OF NON-CALCULOUS URETEROPELVIC OBSTRUCTION. PMID- 17856688 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17856687 TI - THE TREATMENT OF COMPOUND FRACTURES WITH SPECIAL REFERENCE TO THE ORR METHOD. PMID- 17856689 TI - RESPIRATORY PHYSIOLOGY IN THORACIC SURGERY. PMID- 17856690 TI - SURGERY FOR CERVICAL RIBS. PMID- 17856691 TI - POSTERIOR DRAINAGE IN SUPPURATIVE PERICARDITIS. PMID- 17856692 TI - PRIMARY CARCINOMA OF THE BRONCHUS TREATED SUCCESSFULLY WITH SURGICAL DIATHERMY. PMID- 17856693 TI - CARCINOMA FOLLOWING GASTRIC AND DUODENAL ULCER. PMID- 17856694 TI - PRIMARY CARCINOMA OF THE LUNG OR BRONCHUS. PMID- 17856695 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17856696 TI - THE SURGICAL RISK: WITH SPECIAL REFERENCE TO THE CARDIOVASCULAR SYSTEM. PMID- 17856697 TI - JOSHUA CLAPP HUBBARD 1869-1934. PMID- 17856699 TI - JOHN EDWARD SUMMERS 1858-1935. PMID- 17856698 TI - JABEZ NORTH JACKSON 1868-1935. PMID- 17856700 TI - THE RENAL PHASE OF SURGICAL RISK. PMID- 17856701 TI - PANTOCAIN IN SPINAL ANESTHESIA. PMID- 17856702 TI - CARBON DIOXIDE ABSORPTION TECHNIC IN ANESTHESIA. PMID- 17856703 TI - PREANESTHESIA NARCOSIS WITH PARALDEHYDE. PMID- 17856704 TI - SIMPLE DERMOID CYSTS OF THE BREAST. PMID- 17856705 TI - TUBERCULOSIS OF THE BREAST. PMID- 17856706 TI - ACUTE CHOLECYSTITIS ASSOCIATED WITH PANCREATIC REFLUX. PMID- 17856708 TI - APPENDICITIS: AN ANALYSIS OF 4,833 CASES. PMID- 17856707 TI - SURGERY OF THE GALLBLADDER AND BILIARY TRACT. PMID- 17856709 TI - SPINA BIFIDA: TREATMENT AND ANALYSIS OF EIGHTY-FOUR CASES. PMID- 17856710 TI - BILATERAL TRIGEMINAL TIC: ITS ASSOCIATION WITH HEREDITY AND DISSEMINATED SCLEROSIS. PMID- 17856711 TI - PENETRATING WOUNDS OF THE BRAIN: AN EXPERIMENTAL STUDY. PMID- 17856712 TI - PULSATING TUMORS OF THE STERNUM: REPORT OF FOUR CASES. PMID- 17856713 TI - CHOLANGIOGRAPHY: VISUALIZATION OF THE GALLBLADDER AND BILE DUCTS DURING AND AFTER OPERATION. PMID- 17856714 TI - DIVERTICULOSIS OF THE SMALL INTESTINE. PMID- 17856715 TI - THE PROBLEM OF THE LOW SIGMOIDAL GROWTH. PMID- 17856716 TI - CARCINOMA OF LINITIS PLASTICA TYPE INVOLVING THE INTESTINE. PMID- 17856717 TI - ACUTE REGIONAL ILEITIS. PMID- 17856718 TI - UNUSUAL INFLAMMATORY LESIONS OF THE ILEOCECAL REGION. PMID- 17856719 TI - PRIMARY CARCINOMA OF THE FALLOPIAN TUBES: REPORT OF TWO CASES. PMID- 17856720 TI - FRACTURES OF THE HUMERUS: ANALYSIS OF TREATMENT AND RESULTS OF 200 FRACTURES. PMID- 17856721 TI - OSTEITIS PUBIS FOLLOWING SUPRAPUBIC PROSTATECTOMY. PMID- 17856722 TI - MEMOIR: HAYWARD W. CUSHING 1854-1934. PMID- 17856724 TI - CONGENITALLY SHORTENED ESOPHAGUS (THORACIC STOMACH): REPORT OF TWO CASES FOUND POSTMORTEM. PMID- 17856723 TI - LIVER STONES. PMID- 17856725 TI - EXTENSION OF GASTRIC CARCINOMA INTO THE DUODENUM. PMID- 17856727 TI - FACTORS IN THE MORTALITY OF ACUTE APPENDICITIS. PMID- 17856726 TI - GASTRIC AND DUODENAL PERFORATION DURING HOSPITAL TREATMENT. PMID- 17856728 TI - THE TREATMENT OF GASEOUS DISTENTION OF THE INTESTINE BY THE INHALATION OF NINETY FIVE PER CENT OXYGEN: DESCRIPTION OF AN APPARATUS FOR THE CLINICAL ADMINISTRATION OF HIGH OXYGEN MIXTURES. PMID- 17856729 TI - CYST OF WOLFFIAN ORIGIN WITH APLASIA OF KIDNEY AND URETER, HYDRONEPHROSIS AND UNDESCENDED TESTICLE. PMID- 17856730 TI - RENAL LIPOMATOSIS. PMID- 17856731 TI - TRUE HERMAPHRODITISM: REPORT OF A CASE WITH NECROPSY. PMID- 17856732 TI - PRIMARY CARCINOMA OF THE EXTREMITIES. PMID- 17856734 TI - LEPTOTHRICOSIS: PULMONARY ABSCESS AND FATAL PYEMIA. PMID- 17856733 TI - ELECTROSURGERY IN ADVANCED CARCINOMA. PMID- 17856735 TI - FRACTURES OF THE JAW AND ALLIED TRAUMATIC LESIONS OF THE FACIAL STRUCTURES. PMID- 17856737 TI - VOLKMANN'S ISCHEMIC CONTRACTURE IN HEMOPHILIA. PMID- 17856736 TI - THE NICOLA OPERATION FOR RECURRENT DISLOCATION OF THE SHOULDER. PMID- 17856738 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17856739 TI - MEMOIR: AUGUST FREDERICK JONAS 1858-1934. PMID- 17856740 TI - THE SURGICAL TREATMENT OF SYRINGOMYELIA. PMID- 17856741 TI - COMPLETE SYMPATHECTOMY: OBSERVATIONS OF CERTAIN VASCULAR REACTIONS DURING AND AFTER COMPLETE EXCLUSION OF THE SYMPATHETIC NERVOUS SYSTEM IN DOGS AN EXPERIMENTAL STUDY. PMID- 17856742 TI - LUMBAR GANGLIONECTOMY AND TRUNK RESECTION IN CHRONIC ARTHRITIS. PMID- 17856743 TI - THE THERAPEUTIC EFFECTS FOLLOWING INTERRUPTION OF THE SYMPATHETIC NERVES: REPORT ON THE ALCOHOL BLOCK IN CERTAIN ARTHRITIC AND VASCULAR CASES. PMID- 17856745 TI - TUMORS OF THE CAROTID BODY. PMID- 17856744 TI - THE USE OF AVERTIN (TRI-BROM-ETHANOL) IN NEUROSURGERY. PMID- 17856746 TI - DIGESTIVE PHENOMENA IN THE PSYCHOPATHIC PATIENT. PMID- 17856747 TI - LIVER STONES. PMID- 17856748 TI - TRUE PROLIFERATING CYSTIC LYMPHANGIOMA OF THE MESENTERY. PMID- 17856750 TI - THE ORR TREATMENT OF PYOGENIC OSTEOMYELITIS. PMID- 17856749 TI - CONSERVATIVE TREATMENT OF ACUTE HEMATOGENOUS OSTEOMYELITIS. PMID- 17856751 TI - END-RESULTS OF EXCISION OF THE ELBOW. PMID- 17856753 TI - PRESIDENTIAL ADDRESS: THE MASTER SURGEON AND THE LAYMAN. PMID- 17856752 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17856754 TI - BRAIN ABSCESS. PMID- 17856755 TI - THE SURGICAL TREATMENT OF EPILEPTIFORM SEIZURES. PMID- 17856756 TI - CARCINOMA OF THE BREAST: A STUDY OF THE FIVE YEAR END-RESULTS. PMID- 17856758 TI - SUPPURATIVE PERICARDITIS: LATE RESULTS AND METHODS OF DRAINAGE. PMID- 17856757 TI - THE ULTIMATE PHASE OF LIFE AS IT RELATES TO WOUNDS OF THE HEART. PMID- 17856759 TI - THE DEVELOPMENT OF SELECTIVE EXTRAPLEURAL THORACOPLASTY FOR PULMONARY TUBERCULOSIS. PMID- 17856761 TI - THE SURGICAL TREATMENT OF CONGENITAL TRACHEO-ESOPHAGEAL FISTULA IN THE NEW-BORN. PMID- 17856760 TI - THE TECHNIC OF THORACOPLASTY FOR PULMONARY TUBERCULOSIS. PMID- 17856762 TI - ULCER OF THE PYLORIC SPHINCTER. PMID- 17856764 TI - OBSTRUCTION OF THE SMALL INTESTINE DUE TO FOOD PRODUCTS. PMID- 17856763 TI - MECKEL'S DIVERTICULUM WITH PEPTIC ULCER. PMID- 17856765 TI - SHOULDER AND CLAVICULAR PAIN IN APPENDICITIS. PMID- 17856766 TI - SERIOUS COMPLICATIONS FOLLOWING NEGLECTED CHOLELITHIASIS. PMID- 17856768 TI - ABDOMINAL GAS BACILLUS CATASTROPHES. PMID- 17856767 TI - THE TREATMENT OF AMEBIC ABSCESS OF THE LIVER. PMID- 17856769 TI - INGUINAL HERNIA. PMID- 17856770 TI - SURGICAL TREATMENT OF GIANT CELL TUMOR. PMID- 17856771 TI - SOME OF THE HAZARDS OF IRRADIATION. PMID- 17856772 TI - TUMORS OF THE KIDNEY. PMID- 17856773 TI - ATRAUMATIC REMOVAL OF NEEDLE FROM HAND: UNDER FLUOROSCOPIC CONTROL. PMID- 17856774 TI - HERBERT PHALON COLE 1880-1935. PMID- 17856775 TI - FRANKLIN H. MARTIN 1857-1935. PMID- 17856776 TI - EDITORIAL. PMID- 17856777 TI - THE DIAGNOSIS AND TREATMENT OF OSTEOMYELITIS. PMID- 17856778 TI - JOHN ROACH WATHEN 1872-1935. PMID- 17856779 TI - JOHN SMYTH 1869-1935. PMID- 17856780 TI - ERNEST SYDNEY LEWIS 1840-1935. PMID- 17856781 TI - REPORT OF THE COMMITTEE TO STUDY FURTHER PROBLEMS OF POSTGRADUATE SURGICAL EDUCATION IN GENERAL AND THE QUALIFICATIONS FOR SPECIALIZATION IN GENERAL SURGERY IN PARTICULAR. PMID- 17856782 TI - BACTERIOLOGIC STUDIES OF CHRONIC APPENDICITIS: BASED UPON 209 CONSECUTIVE CASES. PMID- 17856783 TI - THE BILE TRACT AND ACUTE PANCREATITIS. PMID- 17856784 TI - PRESACRAL NERVE RESECTION FOR THE RELIEF OF PELVIC PAIN AND DYSMENORRHEA. PMID- 17856785 TI - PRESACRAL SYMPATHECTOMY FOR DYSMENORRHEA AND PELVIC PAIN. PMID- 17856786 TI - TOTAL HYSTERECTOMY: A REVIEW OF 177 CASES. PMID- 17856787 TI - NEPHROPEXY FOR DISABILITIES DUE TO ABNORMAL RENAL MOBILITY. PMID- 17856788 TI - CAUTIONS IN THE TREATMENT OF URETERAL CALCULI. PMID- 17856789 TI - CYSTS OF THE TESTICLE. PMID- 17856790 TI - SUCCESSFUL OPERATIONS FOR HYPOSPADIAS. PMID- 17856791 TI - END-TO-END VASCULAR ANASTOMOSIS: AN EXPERIMENTAL STUDY. PMID- 17856792 TI - ARTERIOVENOUS ANEURYSM OF THE FIRST PORTION OF THE RIGHT SUBCLAVIAN ARTERY AND INNOMINATE VEIN: REPORT OF A CASE SUCCESSFULLY OPERATED UPON. PMID- 17856794 TI - FRACTURES OF THE HUMERUS WITH PARTICULAR REFERENCE TO NON-UNION AND ITS TREATMENT. PMID- 17856793 TI - CLOSED REDUCTION OF RECENT DISLOCATIONS OF THE SEMILUNAR (LUNATE) BONE: WITH RESULTS AND DISCUSSION REGARDING NECROSIS (MALACIA) REPORT OF ELEVEN CASES. PMID- 17856795 TI - A FORGOTTEN CHAPTER IN THE HISTORY OF THE CIRCULATION OF THE BLOOD. PMID- 17856796 TI - BILATERAL ASEPTIC NECROSIS OF THE FEMORAL HEAD: PROBLEMS ARISING IN A COMPENSATION CASE. PMID- 17856797 TI - THE TREATMENT OF OLD UNREDUCED NASAL FRACTURES. PMID- 17856798 TI - DISLOCATION AND ELONGATION OF THE LONG HEAD OF THE BICEPS BRACHII: AN ANALYSIS OF SIX CASES. PMID- 17856799 TI - LIPOMA OF THE EXTREMITIES. PMID- 17856800 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17856801 TI - MEMOIR: WILLIS FOREMAN WESTMORELAND 1864-1935. PMID- 17856802 TI - METASTASES TO THE THYROID GLAND FROM CANCER OF THE COLON. PMID- 17856803 TI - THE FALL IN BLOOD PRESSURE DURING SPINAL ANESTHESIA. PMID- 17856804 TI - EVIPAL ANESTHESIA IN THORACIC SURGERY: STUDIES IN ONE HUNDRED THORACOPLASTIES FOR PULMONARY TUBERCULOSIS. PMID- 17856805 TI - LOCAL PROPHYLACTIC USE OF ANTIGAS GANGRENE SERUM. PMID- 17856806 TI - ACUTE INTESTINAL OBSTRUCTION BY THE PERSIMMON PHYTOBEZOAR: REPORT OF TWO CASES. PMID- 17856807 TI - TRANSVERSE INCISION IN THE UPPER ABDOMEN: ITS ANATOMIC AND PHYSIOLOGIC ADVANTAGES. PMID- 17856808 TI - EXPERIMENTAL STUDIES OF URETERO-INTESTINAL ANASTOMOSIS: A PRELIMINARY REPORT. PMID- 17856810 TI - THE SURGICAL TREATMENT OF IRREMOVABLE CANCER OF THE PYLORIC SEGMENT OF THE STOMACH. PMID- 17856809 TI - THE SURGICAL TREATMENT OF HYPERPARATHYROIDISM: BASED ON 30 CASES CONFIRMED BY OPERATION. PMID- 17856811 TI - MYCOTIC INFECTION OF THE STOMACH: REPORT OF A CASE WITH PERFORATION. PMID- 17856812 TI - PATHOLOGIC CHANGES IN EXTERIORIZED GASTRO-INTESTINAL GRAFTS. PMID- 17856813 TI - SOLID TUMORS OF THE MESENTERY. PMID- 17856814 TI - MECHANISM AND SIGNIFICANCE OF OBLITERATION OF THE LUMEN OF THE VERMIFORM APPENDIX. PMID- 17856815 TI - POSTANGINAL SEPSIS: CAUSED BY A NEWLY DESCRIBED HEMOPHYLIC ANAEROBIC BACILLUS. PMID- 17856816 TI - ASPIRATION OF BREAST CYSTS. PMID- 17856817 TI - CHRONIC PROGRESSIVE POSTOPERATIVE GANGRENE OF THE ABDOMINAL WALL. PMID- 17856818 TI - THE ELECTIVE TRANSVERSE ABDOMINAL INCISION. PMID- 17856819 TI - SACROCOCCYGEAL TRANSRECTAL APPROACH FOR REPAIR OF HIGH RECTOVAGINAL AND VESICOVAGINAL FISTULAE. PMID- 17856821 TI - STRICTURES OF THE PROSTATICO-MEMBRANOUS URETHRA: NEWER METHODS IN THE MANAGEMENT OF DIFFICULT LESIONS. PMID- 17856820 TI - URETERAL TRANSPLANTATION AND CYSTECTOMY. PMID- 17856822 TI - RECTAL STRICTURE DUE TO LYMPHOPATHIA VENEREUM: A CLINICAL AND PATHOLOGIC STUDY OF SIX CASES OBSERVED AT NECROPSY. PMID- 17856823 TI - SUPPURATIVE ARTHRITIS OF THE SACRO-ILIAC JOINT. PMID- 17856824 TI - SERUM PHOSPHATASE IN FRACTURE REPAIR. PMID- 17856825 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17856826 TI - THE RESTORATION OF DEFECTS IN THE SKULL: WITH SPECIAL REFERENCE TO THE MANAGEMENT OF INTRINSIC TUMORS OF THE SKULL AND CERTAIN TYPES OF LOCALIZED OSTEOMYELITIS. PMID- 17856827 TI - COMPARATIVE STUDIES ON TRAUMATIC SHOCK UNDER ETHER AND UNDER SODIUM AMYTAL ANESTHESIA: AN EXPERIMENTAL RESEARCH. PMID- 17856828 TI - MODIFIED DORSAL SYMPATHECTOMY FOR VASCULAR SPASM (RAYNAUD'S DISEASE) OF THE UPPER EXTREMITY: A PRELIMINARY REPORT. PMID- 17856829 TI - RESECTION OF THE PRESACRAL NERVE FOR DYSMENORRHEA AND PELVIC PAIN. PMID- 17856830 TI - EXPERIMENTAL PRODUCTION OF CHYLOTHORAX BY OCCLUSION OF THE SUPERIOR VENA CAVA. PMID- 17856831 TI - ACUTE SUPPURATIVE PERICARDITIS. PMID- 17856832 TI - GASTRODUODENAL SURGERY. PMID- 17856833 TI - PERITONITIS AS A FACTOR IN THE MORTALITY OF GASTRO-INTESTINAL SURGERY. PMID- 17856834 TI - INDUCED AND SPONTANEOUS CHANGES IN BLOOD AMYLASE PARTICULARLY IN RELATIONSHIP TO THE PANCREAS: AN EXPERIMENTAL STUDY. PMID- 17856835 TI - INGUINAL HERNIA: A REPORT OF 1,600 OPERATIONS. PMID- 17856836 TI - TETANUS: EXPERIENCE IN THE EPISCOPAL HOSPITAL IN THE PAST 30 YEARS (1905-1935). PMID- 17856837 TI - PERINEAL PROSTATECTOMY: A SURVEY OF 67 CONSECUTIVE CASES. PMID- 17856838 TI - RHABDOMYOSARCOMA OF THE NECK. PMID- 17856839 TI - THE SURGICAL TREATMENT OF TUMORS OF THE PERIPHERAL NERVES. PMID- 17856840 TI - BENIGN METASTASIZING HEMANGIOMA. PMID- 17856842 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17856841 TI - THE IMPORTANCE IN SURGERY OF THE BLOOD CIRCULATION TIME. PMID- 17856843 TI - ADDRESS OF THE PRESIDENT: THE MAKING OF A SURGEON. PMID- 17856844 TI - STUDIES IN BRAIN INJURY: -INCREASED CEREBROSPINAL FLUID PRESSURE FROM BLOOD IN THE CEREBROSPINAL FLUID: AN EXPERIMENTAL STUDY. PMID- 17856845 TI - REACTIONS FOLLOWING OPERATIONS FOR HYPERTHYROIDISM. PMID- 17856846 TI - PERICARDIAL RESECTION IN CHRONIC CONSTRICTIVE PERICARDITIS. PMID- 17856848 TI - SOME ADVANCES IN THE TECHNIC OF THORACOPLASTY. PMID- 17856847 TI - TUMORS OF THE CHEST WALL. PMID- 17856849 TI - THE LATE RESULTS OF THORACOPLASTY IN THE TREATMENT OF PULMONARY TUBERCULOSIS. PMID- 17856850 TI - THE USE OF INTERCOSTAL MUSCLE IN THE CLOSURE OF BRONCHIAL FISTULAE. PMID- 17856851 TI - TRAUMATIC SURGERY OF THE LUNGS AND PLEURA: ANALYSIS OF 1,009 CASES OF PENETRATING WOUNDS. PMID- 17856852 TI - A TEN YEAR STUDY OF EMPYEMA IN CHILDREN: 1926-1936. PMID- 17856853 TI - GASTRIC ACIDITY FOLLOWING OPERATIONS FOR GASTRIC AND DUODENAL ULCER: ITS EFFECT ON THE QUESTION OF PARTIAL GASTRECTOMY. PMID- 17856854 TI - A TECHNIC FOR THE MANAGEMENT OF GASTROJEJUNAL ULCERS WITH OR WITHOUT GASTROCOLIC OR JEJUNOCOLIC FISTULA. PMID- 17856855 TI - EXPERIMENTAL LYMPHEDEMA OF THE INTESTINAL TRACT AND ITS RELATION TO REGIONAL CICATRIZING ENTERITIS. PMID- 17856856 TI - THE REDUCTION OF THE INCREASING MORTALITY AND MORBIDITY IN ACUTE APPENDICITIS. PMID- 17856857 TI - RESECTION OF THE RECTUM AND RECTOSIGMOID BY SINGLE OR GRADED PROCEDURES. PMID- 17856858 TI - THE ONE STAGE PROCEDURE OF THE TREATMENT OF CARCINOMA OF THE RECTUM. PMID- 17856859 TI - IMPERFORATE ANUS WITH RECTOVAGINAL CLOACA. PMID- 17856860 TI - OPERATIVE INSULIN CRISIS IN RESECTION OF THE PANCREAS. PMID- 17856861 TI - BENIGN CICATRICIAL STRICTURES OF THE BILE DUCTS. PMID- 17856862 TI - CHOLECYSTODUODENOSTOMY COMBINED WITH PYLORIC EXCLUSION. PMID- 17856863 TI - TWENTY-FIVE YEARS' EXPERIENCE IN THE TREATMENT OF PERITONITIS. PMID- 17856864 TI - THE PREVENTION OF PERITONEAL ADHESIONS BY PAPAIN: A CLINICAL STUDY. PMID- 17856865 TI - DELAYED WOUND HEALING FOLLOWING NEPHRECTOMY FOR TUBERCULOSIS: ANALYSIS OF CAUSE. PMID- 17856866 TI - THE ROLE OF SURGERY IN THE TREATMENT OF ACTINOMYCOSIS. PMID- 17856867 TI - THE SURGICAL TREATMENT OF ESSENTIAL HYPERTENSION. PMID- 17856868 TI - THE DEMONSTRATION OF HORMONES IN TUMORS. PMID- 17856869 TI - MEMOIR: EDWARD STARR JUDD 1878-1935. PMID- 17856870 TI - DESTRUCTION OF THE CEREBRAL CORTEX FOLLOWING NITROUS OXIDE-OXYGEN-ANESTHESIA. PMID- 17856871 TI - THE PHYSIOLOGY OF MASSIVE PULMONARY EMBOLISM: AN EXPERIMENTAL STUDY OF THE CHANGES PRODUCED BY OBSTRUCTION TO THE FLOW OF BLOOD THROUGH THE PULMONARY ARTERY AND ITS LOBAR BRANCHES. PMID- 17856872 TI - PULMONARY EMBOLECTOMY. PMID- 17856873 TI - ACUTE PERFORATION OF GASTROJEJUNAL ULCER: REPORT OF TEN NEW CASES AND A REVIEW OF NINETY-THREE COLLECTED CASES. PMID- 17856874 TI - LATE RESULTS IN ACUTE PERFORATED PEPTIC ULCER TREATED BY SIMPLE CLOSURE. PMID- 17856875 TI - OBSTRUCTIONS ABOUT THE MESENTERY IN INFANTS. PMID- 17856876 TI - SPLENECTOMY FOR HEMOCLASTIC CRISES. PMID- 17856877 TI - AN ANATOMIC RESTUDY OF THE PELVIC LYMPHATICS. PMID- 17856878 TI - TRANSURETHRAL RESECTION. PMID- 17856879 TI - RELIEF OF PAIN BY PERIPHERAL NERVE BLOCK IN ARTERIAL DISEASES OF THE LOWER EXTREMITIES. PMID- 17856880 TI - NERVE INJURY IN FRACTURE OF THE PELVIS. PMID- 17856881 TI - THE INFLUENCE OF HEREDITY IN CANCER. PMID- 17856882 TI - TOTAL GASTRECTOMY. PMID- 17856883 TI - DIVERTICULA OF THE VERMIFORM APPENDIX: A STUDY BASED ON THIRTY CASES. PMID- 17856884 TI - THE USE OF GLYCERYL TRINITRATE (NITROGLYCERIN) FOR THE CONTROL OF PAIN FOLLOWING CHOLECYSTECTOMY. PMID- 17856885 TI - AN OPERATIVE PROCEDURE FOR RIGHT-SIDED ULCERATIVE ILEOCOLITIS. PMID- 17856887 TI - THE INTRAPERITONEAL APPROACH FOR REPAIR OF INGUINAL HERNIA. PMID- 17856886 TI - THE SURGICAL TREATMENT OF FIVE HUNDRED HERNIAE. PMID- 17856888 TI - CORRELATION OF PATHOLOGIC AND ROENTGENOLOGIC FINDINGS IN TUBERCULOSIS AND PYOGENIC INFECTIONS OF THE VERTEBRAE: THE FATE OF THE INTERVERTEBRAL DISK. PMID- 17856889 TI - GIANT CELL TUMORS OF THE JAWS. PMID- 17856891 TI - THE SURGICAL TREATMENT OF HUMAN BITES. PMID- 17856890 TI - SUBCHONDRAL TUBERCULOUS SEQUESTRA. PMID- 17856893 TI - STAGE OPERATIONS IN SEVERE HYPERTHYROIDISM. PMID- 17856892 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17856894 TI - HYPERPARATHYROIDISM IN SIBLINGS. PMID- 17856895 TI - CYCLOPROPANE ANESTHESIA IN THYROIDECTOMY. PMID- 17856896 TI - THE PROBLEM OF MYOSITIS OSSIFICANS PROGRESSIVA. PMID- 17856897 TI - DIVISION OF RIBS AS AN AID IN CLOSING A DIAPHRAGMATIC HERNIA. PMID- 17856898 TI - COMPLICATIONS OF GALLBLADDER SURGERY. PMID- 17856899 TI - PROPHYLACTIC FOOT TREATMENT IN PATIENTS WITH DIABETES MELLITUS: ANALYSES OF ITS EFFECT ON THE PREVENTION OF INFECTION OF THE LOWER EXTREMITIES AND THE OPERATIVE PROGNOSIS IN A SERIES OF FIVE HUNDRED SEVENTY-SIX CASES. PMID- 17856900 TI - ADAMANTINOMA OF THE JAW. PMID- 17856901 TI - UNUNITED FRACTURES OF THE SHAFT OF THE HUMERUS. PMID- 17856903 TI - WILLIAM BRADLEY COLEY 1862-1936. PMID- 17856902 TI - JOSEPH COLT BLOODGOOD 1867-1935. PMID- 17856904 TI - CARL ARTHUR HEDBLOM 1879-1934. PMID- 17856905 TI - JONATHAN MAYHEW WAINWRIGHT 1874-1934. PMID- 17856906 TI - SURGICAL ASPECTS OF ADENOMA OF THE LIVER. PMID- 17856907 TI - PERFORATED PEPTIC ULCER IN MECKEL'S DIVERTICULUM: REPORT OF A CASE OCCURRING INTRAMESENTERIC. PMID- 17856908 TI - MORTALITY IN ACUTE APPENDICITIS. PMID- 17856909 TI - DRAINAGE OF THE ABDOMEN. PMID- 17856910 TI - EXPERIMENTAL STUDIES IN CAROTID-JUGULAR ANASTOMOSIS: WITH SPECIAL REFERENCE TO THE ROLE OF THE CAROTID SINUS. PMID- 17856911 TI - MORTALITY IN SURGICAL DISEASES OF THE BILIARY TRACT: AN ANALYSIS OF ONE HUNDRED AND THIRTY AUTOPSIES. PMID- 17856912 TI - THE TREATMENT OF TETANUS WITH ANTITOXIN: AN ANALYSIS OF THE OUTCOME IN SIX HUNDRED FORTY-TWO CASES. PMID- 17856913 TI - ACUTE SUPPURATIVE TENOSYNOVITIS OF THE FLEXOR TENDON SHEATHS OF THE HAND: A REVIEW OF ONE HUNDRED AND TWENTY-FIVE CASES. PMID- 17856914 TI - THE TOPOGRAPHY OF THE EXTRAHEPATIC BILIARY PASSAGES: WITH REFERENCE TO DANGERS OF SURGICAL TECHNIC. PMID- 17856915 TI - TUBERCULOSIS OF THE BREAST. PMID- 17856916 TI - MEDIASTINAL TUMOR CAUSED BY HODGKIN'S DISEASE. PMID- 17856917 TI - JEJUNAL INTUSSUSCEPTION. PMID- 17856918 TI - CONGENITAL ATRESIA OF THE INTESTINE. PMID- 17856919 TI - RECTAL PROLAPSE: EXPERIENCE WITH THE ELASTIC LIGATURE. PMID- 17856920 TI - TUMORS OF THE UTERUS: WITH SPECIAL REFERENCE TO FIBROIDS. PMID- 17856921 TI - PRIMARY CARCINOMA OF THE MALE URETHRA. PMID- 17856922 TI - SEVERED TENDONS AND NERVES OF THE HAND AND FOREARM. PMID- 17856923 TI - PAINFUL SHOULDER: ARISING FROM LESIONS OF THE SUBACROMIAL BURSA AND SUPRASPINATUS TENDON. PMID- 17856924 TI - GAS GANGRENE: A REVIEW OF THIRTY-TWO CASES WITH SPECIAL REFERENCE TO THE USE OF SERUM, BOTH PROPHYLACTIC AND THERAPEUTIC. PMID- 17856925 TI - A CORRELATION OF ROENTGEN RAY DOSAGE AND NECROPSY FINDINGS IN A CASE OF RETROPERITONEAL AND MEDIASTINAL METASTASES FROM EMBRYONAL CARCINOMA OF THE TESTIS: DEATH FROM GANGRENE OF THE COLON, THE RESULT OF IRRADIATION THERAPY. PMID- 17856926 TI - TISSUE HEATING ACCOMPANYING ELECTROSURGERY: AN EXPERIMENTAL INVESTIGATION. PMID- 17856927 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17856929 TI - FRANCIS STUART MATHEWS 1869-1936. PMID- 17856928 TI - JOHN FOX CONNORS 1873-1935. PMID- 17856930 TI - MALCOLM LaSALLE HARRIS 1862-1936. PMID- 17856931 TI - LEONARD FREEMAN 1860-1935. PMID- 17856932 TI - WILLIAM JOHNSON TAYLOR 1861-1936. PMID- 17856933 TI - JAMES TATE MASON 1882-1936. PMID- 17856934 TI - THE STATUS OF THE INJECTION TREATMENT OF HERNIA. PMID- 17856935 TI - THE AMBULANT TREATMENT OF HERNIA. PMID- 17856936 TI - AN EVALUATION OF THE RESULTS OF THE INJECTION TREATMENT OF INGUINAL HERNIA: A REVIEW OF THE EMPLOYMENT OF THIS METHOD AT THE UNIVERSITY OF MINNESOTA HOSPITAL. PMID- 17856937 TI - THE INJECTION TREATMENT OF HERNIA: AN EVALUATION OF THE TECHNIC AND RESULTS. PMID- 17856938 TI - STERILITY FOLLOWING THE INJECTION TREATMENT OF HERNIA: A DETERMINATION OF ITS INCIDENCE. PMID- 17856939 TI - THE VALUE OF PARTIAL PANCREATECTOMY IN CONVULSIVE STATES ASSOCIATED WITH HYPOGLYCEMIA. PMID- 17856940 TI - THE THYROID GLAND IN HYPOGLYCEMIA. PMID- 17856942 TI - THE VALUE OF PREOPERATIVE IRRADIATION IN TUMOR OF THE TESTIS. PMID- 17856941 TI - THE VARIATIONS OF BLOOD AMYLASE DURING ACUTE TRANSIENT DISEASE OF THE PANCREAS. PMID- 17856943 TI - SHOCK SYNDROME FOLLOWING SUBCUTANEOUS INJECTION OF BILE OR BILE SALTS. PMID- 17856944 TI - SPINAL EXTRADURAL CYSTS. PMID- 17856945 TI - SACROCOCCYGEAL TERATOMA. PMID- 17856946 TI - CANCER OF THE TONGUE: A REPORT OF ONE HUNDRED AND EIGHTY-SEVEN CASES, WITH AN ANALYSIS OF NINETY-EIGHT TREATED PRINCIPALLY BY SURGERY AT THE NEW YORK SKIN AND CANCER HOSPITAL BETWEEN 1917 AND 1935. PMID- 17856948 TI - SUBASTRAGALAR ARTHRODESIS IN PARALYTIC DEFORMITIES. PMID- 17856947 TI - THE CARE AND CURE OF CANCER PATIENTS. PMID- 17856949 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17856950 TI - SURGERY IN PATIENTS OF ADVANCED AGE. PMID- 17856951 TI - SUBPHRENIC ABSCESS WITH BRONCHIAL FISTULA. PMID- 17856952 TI - DRAINAGE OF THE ABDOMINAL CAVITY IN OPERATIONS FOR PERFORATED PEPTIC ULCER. PMID- 17856953 TI - MULTIPLE POLYPOSIS OF THE COLON: A FAMILIAL DISEASE. PMID- 17856954 TI - THE EVALUATION OF ABDOMINAL SYMPTOMS IN THE DIABETIC. PMID- 17856955 TI - SARCOMA OF THE KIDNEY IN ADULTS. PMID- 17856956 TI - PYOUMBILICUS ASSOCIATED WITH UMBILICAL CONCRETIONS. PMID- 17856957 TI - FEMORAL HERNIA IN THE MALE. PMID- 17856958 TI - CERVICAL RIB AND THE SCALENUS ANTICUS SYNDROME. PMID- 17856959 TI - FIBROUS OSTEOMA OF THE JAWS. PMID- 17856960 TI - FRACTURE OF THE FEMUR IN CHILDREN. PMID- 17856961 TI - GANGLIA AND SYNOVIAL CYSTS: THEIR PATHOGENESIS AND TREATMENT. PMID- 17856962 TI - TWENTY YEARS' EXPERIENCE WITH THE CITRATE METHOD OF BLOOD TRANSFUSION. PMID- 17856963 TI - FATTY ACID SOLUTIONS FOR THE INJECTION TREATMENT OF VARICOSE VEINS: EVALUATION OF FOUR NEW SOLUTIONS. PMID- 17856964 TI - VITAMIN C DEFICIENCY AND WOUND HEALING: AN EXPERIMENTAL AND CLINICAL STUDY. PMID- 17856965 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17856966 TI - REA SMITH 1876-1935. PMID- 17856967 TI - CHARLES HARRISON FRAZIER 1870-1936. PMID- 17856968 TI - PRESIDENTIAL ADDRESS: WIDER HORIZONS FOR THE SURGEON. PMID- 17856969 TI - SURGICAL TREATMENT OF FACIAL SPASM. PMID- 17856970 TI - DIRECT ROENTGEN RADIATION OF BRAIN TUMORS DURING OPERATION. PMID- 17856971 TI - THE TREATMENT OF BRAIN TRAUMA. PMID- 17856972 TI - ANEURYSM IN THE CERVICAL PORTION OF THE INTERNAL CAROTID ARTERY: AN ANALYTICAL STUDY OF THE CASES RECORDED IN THE LITERATURE BETWEEN AUGUST 1, 1925, AND JULY 31, 1936 REPORT OF TWO NEW CASES. PMID- 17856973 TI - FURTHER OBSERVATIONS ON THYROID DISEASE IN A NONENDEMIC AREA: AN ANALYSIS OF SIX HUNDRED SIXTY-TWO SURGICAL CASES AND SIXTEEN NONSURGICAL DEATHS. PMID- 17856974 TI - AN ANALYSIS OF THREE HUNDRED CONSECUTIVE THYROIDECTOMIES. PMID- 17856975 TI - TOTAL THYROIDECTOMY FOR HEART DISEASE. PMID- 17856976 TI - FACTORS OF SIGNIFICANCE IN THE PROGNOSIS OF CANCER OF THE STOMACH. PMID- 17856977 TI - CHRONIC OBSTRUCTION AND DILATATION OF THE DUODENUM. PMID- 17856978 TI - THE TECHNIC OF CLOSING PERFORATED ULCER OF THE DUODENUM. PMID- 17856979 TI - THE SURGICAL ASPECTS OF ACUTE CHOLECYSTITIS. PMID- 17856980 TI - STRICTURES OF THE COMMON AND HEPATIC DUCTS. PMID- 17856981 TI - THE SURGICAL TREATMENT OF CHRONIC BILIARY TYPHOID CARRIERS. PMID- 17856982 TI - ACUTE PERFORATED APPENDICITIS WITH PERITONITIS: REPORT OF TWO HUNDRED FIFTY-TWO CONSECUTIVE CASES. PMID- 17856983 TI - THE APPENDIX PROBLEM: A PERENNIAL CAUSE OF PREVENTABLE MORTALITY. PMID- 17856985 TI - REGIONAL ILEITIS. PMID- 17856984 TI - EPIGASTRIC SYMPTOMS IN ACUTE LUNG AND HEART DISEASES. PMID- 17856986 TI - ENTERITIS OF THE OBSTRUCTED LOOP FOLLOWING ENTEROANASTOMOSIS FOR INTESTINAL OBSTRUCTION. PMID- 17856987 TI - A CONTROLLABLE CECOSTOMY. PMID- 17856988 TI - THE ORIGIN AND GROWTH OF RENAL CALCULI. PMID- 17856989 TI - ORGANIZATION OF THE AMERICAN BOARD OF SURGERY COMPLETED. PMID- 17856990 TI - EPHRAIM McDOWELL MEMORIAL. PMID- 17856991 TI - WILLIAM OLIVER FLOYD 1880-1936. PMID- 17856992 TI - CHARLES JEFFERSON MILLER 1874-1936. PMID- 17856993 TI - SOUTHGATE LEIGH 1864-1936. PMID- 17856994 TI - THE TECHNIC OF COLPOPERINEORRHAPHY. PMID- 17856995 TI - ECHINOCOCCUS DISEASE: REPORT OF A CASE OF PRIMARY ECHINOCOCCUS CYST OF THE UTERUS. PMID- 17856996 TI - THE SHROPSHIRE SUPRAVAGINAL PLASTIC OPERATION. PMID- 17856997 TI - THE STATUS OF VAGINAL HYSTERECTOMY IN GYNECOLOGIC SURGERY. PMID- 17856998 TI - A SATISFACTORY METHOD OF REPAIRING CRUCIAL LIGAMENTS. PMID- 17856999 TI - THE EFFECTS ON BONE OF THE PRESENCE OF METALS; BASED UPON ELECTROLYSIS: AN EXPERIMENTAL STUDY. PMID- 17857000 TI - INTERNAL FIXATION IN FRACTURES OF THE NECK OF THE FEMUR. PMID- 17857001 TI - CONGENITAL LYMPHATIC DISEASES-LYMPHANGIOMATA. PMID- 17857002 TI - FIBRO-ANGIOMA OF THE SPLEEN: REPORT OF A CASE IN AN INFANT OF FOUR MONTHS. PMID- 17857003 TI - SUPPURATIVE ADENITIS OF THE ILIAC LYMPH NODES OF HEMOLYTIC STREPTOCOCCAL ORIGIN. PMID- 17857004 TI - THE STUDY OF WOUND HEALING. PMID- 17857005 TI - IS ADEQUATE MASKING ESSENTIAL FOR THE PATIENT'S PROTECTION? PMID- 17857006 TI - THE PATHOGENESIS OF LOCAL TETANUS. PMID- 17857007 TI - INFECTIONS OF THE DANGEROUS AREAS OF THE FACE: THEIR PATHOLOGY AND TREATMENT. PMID- 17857008 TI - RIEDEL'S STRUMA AND STRUMA LYMPHOMATOSA (HASHIMOTO): A COMPARATIVE STUDY. PMID- 17857010 TI - SPINAL ANESTHESIA: A STUDY OF THE POSTOPERATIVE COURSE. PMID- 17857009 TI - THE TOXIN OF BURNS. PMID- 17857011 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857013 TI - LORD MOYNIHAN 1865-1936. PMID- 17857012 TI - EDWARD J. KLOPP 1880-1936. PMID- 17857014 TI - ISAAC SCOTT STONE 1851-1936. PMID- 17857015 TI - WILLIAM BURTON THORNING 1872-1937. PMID- 17857016 TI - JOHN FAIRBAIRN BINNIE 1863-1936. PMID- 17857018 TI - THE TREATMENT OF ACUTE APPENDICITIS. PMID- 17857017 TI - DUODENAL DIAPHRAGM. PMID- 17857019 TI - POLYCYSTIC DISEASE OF THE PANCREAS (DYSONTOGENETIC CYSTS): REPORT OF A CASE WITH PARTIAL PANCREATECTOMY. PMID- 17857020 TI - CULLEN'S SIGN IN ACUTE PANCREATITIS. PMID- 17857021 TI - "LIVER DEATHS" IN GENERAL SURGERY: TWO CASES UNASSOCIATED WITH BILIARY TRACT OPERATIONS. PMID- 17857023 TI - TUMORS OF THE RENAL PELVIS AND URETER. PMID- 17857022 TI - THE FALSE "ACUTE ABDOMEN": I. PSEUDOPERFORATION OF PEPTIC ULCER. PMID- 17857024 TI - PHEOCHROMOCYTOMA WITH DEMONSTRATION OF PRESSOR (ADRENALIN) SUBSTANCE IN THE BLOOD PREOPERATIVELY DURING HYPERTENSIVE CRISES. PMID- 17857025 TI - THE SHELVING OPERATION IN THE TREATMENT OF NEGLECTED OR IRREDUCIBLE CONGENITAL DISLOCATED HIP. PMID- 17857026 TI - THE REDUCTION OF INTRACRANIAL PRESSURE IN CEREBRAL INJURY BY THE INTRAVENOUS USE OF HYPERTONIC SUCROSE SOLUTION. PMID- 17857027 TI - MORBIDITY FOLLOWING GOITER OPERATIONS. PMID- 17857028 TI - THE SURGICAL TREATMENT OF PULMONARY ABSCESS. PMID- 17857029 TI - THE EFFECT OF HISTIDINE ON THE EXPERIMENTAL PRODUCTION OF PEPTIC ULCER. PMID- 17857030 TI - GASTRIC OPERATIONS FOR BENIGN AND MALIGNANT CONDITIONS: A STATISTICAL STUDY. PMID- 17857031 TI - INTUSSUSCEPTION DUE TO INTESTINAL TUMORS. PMID- 17857032 TI - THE SURGICAL CORRECTION OF ANOMALIES IN FIXATION OF THE ASCENDING COLON. PMID- 17857033 TI - THE FALSE "ACUTE ABDOMEN": II. HENOCH'S PURPURA AND ABDOMINAL ALLERGY. PMID- 17857034 TI - FORESKINS AS SKIN GRAFTS. PMID- 17857035 TI - NEUTRALIZATION OF HISTAMINE AND BURN TOXIN. PMID- 17857036 TI - FRACTURES OF THE PELVIS: A REVIEW OF FOUR HUNDRED FORTY-NINE CASES. PMID- 17857037 TI - THE SHELVING OPERATION AS AN ADJUNCT TO OPEN REDUCTION IN CONGENITAL DISLOCATED HIP AND ITS USE IN PARALYTIC AND PATHOLOGIC DISLOCATIONS. PMID- 17857038 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857039 TI - INJECTION METHOD OF TREATING HERNIA. PMID- 17857040 TI - FASCIAL SUTURE OPERATIONS FOR HERNIA: SUMMARY AND END-RESULTS OF ONE THOUSAND, FOUR HUNDRED EIGHTY-FIVE OPERATIONS. PMID- 17857041 TI - SILK SUTURES IN THE REPAIR OF HERNIA. PMID- 17857042 TI - RESULTS OF HERNIOTOMY IN PATIENTS OF MORE THAN FIFTY YEARS OF AGE. PMID- 17857044 TI - SUBPARIETAL RUPTURE OF THE INTESTINE DUE TO MUSCULAR EFFORT: A COMPLICATION OF HERNIA. PMID- 17857043 TI - RECURRENT INGUINAL HERNIA: AN ANALYSIS OF TWO HUNDRED OPERATIONS. PMID- 17857045 TI - REGIONAL ILEITIS AND FIBROPLASTIC APPENDICITIS. PMID- 17857046 TI - TUBERCULOSIS OF THE CERVIX. PMID- 17857048 TI - HUMAN BITE INFECTIONS OF THE HAND. PMID- 17857047 TI - A CYSTOMETRIC STUDY OF THE FUNCTION OF THE URINARY BLADDER. PMID- 17857049 TI - NARROWING OF THE INTERVERTEBRAL FORAMINA AS A CAUSE OF PSEUDORHEUMATIC PAIN. PMID- 17857050 TI - THE REGENERATION OF BONE TRANSPLANTS. PMID- 17857051 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857052 TI - ADDRESS OF THE PRESIDENT: SAMUEL GROSS LOOKS IN ON THE AMERICAN SURGICAL ASSOCIATION. PMID- 17857053 TI - INTRACRANIAL PRESSURE WITHOUT BRAIN TUMOR: DIAGNOSIS AND TREATMENT. PMID- 17857054 TI - THE PLACE OF EXPLORATORY OPERATION IN THE SURGERY OF SUBPHRENIC ABSCESS: A REPORT OF NINE NEGATIVE EXPLORATIONS. PMID- 17857055 TI - THE CONTROL OF THE HEART BEAT BY THE SURGEON: WITH SPECIAL REFERENCE TO VENTRICULAR FIBRILLATION OCCURRING DURING OPERATION. PMID- 17857056 TI - FOREWORD TO SYMPOSIUM ON CANCER. PMID- 17857057 TI - THE ETIOLOGY OF CANCER IN THE LIGHT OF OUR PRESENT KNOWLEDGE. PMID- 17857058 TI - MALIGNANT CHANGES IN THE FORESTOMACH OF RATS: RELATED TO LOW PROTEIN (CASEIN) DIET AND PREVENTED WITH CYSTINE. PMID- 17857059 TI - OUR RESPONSIBILITY TOWARD ORAL CANCER. PMID- 17857060 TI - EPITHELIOMA OF THE LOWER LIP: A SUGGESTED ROUTINE FOR TREATMENT WITH DESCRIPTION OF THE OPERATIVE EXCISION OF THE SUBMENTAL AND SUBMAXILLARY LYMPH NODES. PMID- 17857061 TI - THE RESULTS AND METHODS OF TREATMENT OF CANCER BY RADIATION. PMID- 17857062 TI - THE EFFECT OF RADIATION THERAPY UPON INTRACRANIAL GLIOMATA. PMID- 17857063 TI - THE PLACE OF RADIUM IN THE TREATMENT OF CANCER OF THE BREAST. PMID- 17857064 TI - INTERSTITIAL RADIATION OF CANCER OF THE BREAST: A REVIEW OF NINETY-SIX CASES OF CANCER OF THE BREAST TREATED ACCORDING TO THE TECHNIC OF GEOFFREY KEYNES. PMID- 17857065 TI - THE TREATMENT OF SOME ABDOMINAL CANCERS BY IRRADIATION THROUGH THE OPEN ABDOMEN COMBINED WITH CAUTERY EXCISION. PMID- 17857066 TI - CARCINOMA OF THE CERVIX TREATED BY THE ROENTGEN RAY AND RADIUM. PMID- 17857067 TI - CANCER SURGERY: THE VALUE OF RADICAL OPERATIONS FOR CANCER AFTER THE LYMPHATIC DRAINAGE AREA HAS BECOME INVOLVED. PMID- 17857068 TI - CARCINOMA OF THE BREAST RESULTS OF SURGICAL TREATMENT WHEN THE CARCINOMA OCCURRED IN THE COURSE OF PREGNANCY OR LACTATION AND WHEN PREGNANCY OCCURRED SUBSEQUENT TO OPERATION (1910-1933). PMID- 17857069 TI - RESECTION WITH ASEPTIC END-TO-END ANASTOMOSIS FOR CARCINOMA OF THE COLON. PMID- 17857070 TI - THE DEVELOPMENT OF LABORATORY SERVICE IN A CANCER HOSPITAL. PMID- 17857071 TI - ABNORMAL FUNCTION OF THE COMMON BILE DUCT RESULTING FROM BENIGN CONDITIONS. PMID- 17857072 TI - CONGENITAL ATRESIA OF THE BILE DUCTS. PMID- 17857073 TI - OBSTRUCTIVE JAUNDICE: THE CAUSE AND PREVENTION OF THE BLEEDING DYSCRASIA. PMID- 17857074 TI - MORTALITY IN ACUTE ILEUS: STATISTICAL REPORT OF FOUR HUNDRED FIFTY CASES OPERATED UPON AT THE PRESBYTERIAN HOSPITAL, NEW YORK. PMID- 17857076 TI - POSTOPERATIVE USE OF INSULIN IN THE NONDIABETIC: WITH SPECIAL REFERENCE TO WOUND HEALING. PMID- 17857075 TI - PERINEPHRIC ABSCESS. PMID- 17857077 TI - SKELETAL TRACTION IN THE TREATMENT OF FRACTURES AND DISLOCATIONS OF THE CERVICAL SPINE. PMID- 17857078 TI - RUPTURE OF THE LUMBAR INTERVERTEBRAL DISK: AN ETIOLOGIC FACTOR FOR SO-CALLED "SCIATIC" PAIN. PMID- 17857079 TI - ANESTHESIA AND SURGERY. PMID- 17857080 TI - MEMOIR: LIEUTENANT-GENERAL SIR ALFRED KEOGH, G.C.B., G.C.V.O., C.H. 1857-1936. PMID- 17857081 TI - THE EARLY AND REMOTE EFFECTS OF TOTAL AND PARTIAL PARAVERTEBRAL SYMPATHECTOMY ON BLOOD PRESSURE: AN EXPERIMENTAL STUDY. PMID- 17857082 TI - STUDIES ON THE ETIOLOGY OF RENAL HYPERTENSION. PMID- 17857083 TI - PRODUCTION OF HYPERTENSION BY CONSTRICTING THE ARTERY OF A SINGLE TRANSPLANTED KIDNEY: AN EXPERIMENTAL INVESTIGATION. PMID- 17857085 TI - POSTOPERATIVE THROMBOSIS AND EMBOLISM. PMID- 17857084 TI - EPINEPHRINE HYPERTENSION: THE EFFECT OF THE CONTINUOUS INTRAVENOUS INJECTION OF EPINEPHRINE ON THE BLOOD PRESSURE AN EXPERIMENTAL INVESTIGATION. PMID- 17857086 TI - THE TREATMENT OF EMBOLISM OF THE GREATER ARTERIES. PMID- 17857087 TI - STUDIES IN THE ETIOLOGY OF ACUTE APPENDICITIS: THE SIGNIFICANCE OF THE STRUCTURE AND FUNCTION OF THE VERMIFORM APPENDIX IN THE GENESIS OF APPENDICITIS A PRELIMINARY REPORT. PMID- 17857088 TI - THE REPAIR OF PERIPHERAL NERVE INJURIES. PMID- 17857089 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857091 TI - THE TREATMENT OF EMPYEMA. PMID- 17857090 TI - MEMOIR: RANDOLPH WINSLOW 1852-1937. PMID- 17857092 TI - CARCINOMA OF THE AMPULLA OF VATER. PMID- 17857094 TI - SQUAMOUS CELL CARCINOMA OF THE LOWER RECTUM AND ANUS. PMID- 17857093 TI - MORTALITY FACTORS IN APPENDICITIS WITH PERFORATION. PMID- 17857095 TI - RUPTURE OF THE SUPRASPINATUS TENDON. PMID- 17857096 TI - PLASMA EXUDATION: LOSS OF PLASMA-LIKE FLUID IN VARIOUS CONDITIONS RESEMBLING SURGICAL SHOCK AN EXPERIMENTAL STUDY. PMID- 17857097 TI - WOUND HEALING AND NEOPLASIA: AN EXPERIMENTAL INVESTIGATION. PMID- 17857099 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857098 TI - A NEW METHOD OF PREPARING NONPYROGENIC INTRAVENOUS INFUSION FLUIDS: BASED ON REMOVAL OF PYROGEN BY ADSORPTIVE FILTRATION. PMID- 17857100 TI - THE SURGICAL FOLLOW-UP DEPARTMENT OF THE NEW YORK HOSPITAL. PMID- 17857102 TI - ENDOBRONCHIAL PROBING COMBINED WITH SERIAL SELECTIVE BRONCHOGRAPHY FLUOROSCOPICALLY CONTROLLED. PMID- 17857101 TI - ABSCESS OF THE TONGUE. PMID- 17857103 TI - A SUGGESTED METHOD FOR MORE RAPIDLY CURING EMPYEMA. PMID- 17857104 TI - FURTHER CLINICAL EXPERIENCES WITH NINETY-FIVE PER CENT OXYGEN FOR THE ABSORPTION OF AIR FROM THE BODY TISSUES. PMID- 17857105 TI - INTRAMEDULLARY DERMOID CYST. PMID- 17857107 TI - DUPUYTREN'S CONTRACTURE. PMID- 17857106 TI - TEARS OF THE SUPRASPINATUS TENDON: RESUME OF TWELVE OPERATED CASES. PMID- 17857108 TI - GLOMUS TUMOR: GLOMANGIOMA. PMID- 17857110 TI - RESULTS IN THE OPERATIVE TREATMENT OF MAJOR TRIGEMINAL NEURALGIA. PMID- 17857109 TI - INTERNAL FIXATION FOR RECENT FRACTURES OF THE NECK OF THE FEMUR. PMID- 17857111 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857112 TI - MEMOIR: FRANCIS ALEXANDER CARRON SCRIMGER 1880-1937. PMID- 17857113 TI - SPASMODIC TORTICOLLIS TREATED BY THE PLASTIC REDUCTION OF MOTOR FIBERS OF THE SPINAL ACCESSORY NERVE: REPORT OF TWO CASES. PMID- 17857114 TI - COMPLETE SYMPATHETIC DENERVATION OF THE UPPER EXTREMITY. PMID- 17857115 TI - THE PROPHYLACTIC AND ACTIVE USE OF ZINC PEROXIDE IN FOUL SMELLING MOUTH AND NECK INFECTIONS. PMID- 17857116 TI - GLOSSITIS RHOMBICA MEDIANA. PMID- 17857117 TI - PLASTIC RECONSTRUCTION OF THE ESOPHAGUS. PMID- 17857119 TI - NONSPECIFIC GRANULOMATA OF THE INTESTINE. PMID- 17857118 TI - INFLAMMATORY TUMORS OF THE GASTRO-INTESTINAL TRACT. PMID- 17857120 TI - THE SO-CALLED HEPATO-RENAL SYNDROME. PMID- 17857121 TI - TUMORS VENTRAL TO THE SACRUM. PMID- 17857122 TI - ACUTE INTESTINAL OBSTRUCTION: EVALUATION OF RESULTS IN TWENTY-ONE HUNDRED FIFTY CASES; WITH DETAILED STUDIES OF TWENTY-FIVE SHOWING POTASSIUM AS A TOXIC FACTOR. PMID- 17857123 TI - SHORT-INTERVAL STAGE OPERATIONS FOR SEVERE HYPERTHYROIDISM. PMID- 17857124 TI - FACTORS INFLUENCING PROGNOSIS IN CARCINOMA OF THE BREAST. PMID- 17857125 TI - INTRATRACHEAL SUCTION IN THE MANAGEMENT OF POSTOPERATIVE PULMONARY COMPLICATIONS. PMID- 17857127 TI - STONES IN THE COMMON BILE DUCT. PMID- 17857126 TI - SPONTANEOUS CHOLEDOCHOGASTROSTOMY AND CHOLECYSTOGASTROSTOMY. PMID- 17857128 TI - APPENDICITIS IN ARMY SERVICE: A REPORT OF TWENTY-ONE HUNDRED CASES. PMID- 17857129 TI - VOLVULUS OF THE CECUM AND ASCENDING COLON. PMID- 17857130 TI - ARGENTAFFINE TUMORS OF THE GASTRO-INTESTINAL TRACT: REPORT OF THREE CASES: ONE WITH DISTANT METASTASES. PMID- 17857132 TI - NEOPLASMS OF THE ABDOMINAL WALL: WITH SPECIAL REFERENCE TO MALIGNANT "IMPLANTATION" TUMORS. PMID- 17857131 TI - THE MECHANISM OF SPASTIC VASCULAR DISEASE AND ITS TREATMENT. PMID- 17857133 TI - BLOOD LOSS IN NEUROSURGICAL OPERATIONS. PMID- 17857134 TI - GIANT CELL TUMOR OF THE CERVICAL SPINE. PMID- 17857136 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857135 TI - RATIONALE OF BONE DRILLING IN DELAYED AND UNUNITED FRACTURES. PMID- 17857138 TI - ACUTE ILEUS: ANALYSIS OF ONE HUNDRED THIRTY CASES OPERATED UPON AT THE PRESBYTERIAN HOSPITAL, NEW YORK CITY. FROM 1932 TO 1935, INCLUSIVE. PMID- 17857137 TI - MEMOIR: INGERSOLL OLMSTED 1864-1936. PMID- 17857139 TI - ACUTE INTESTINAL OBSTRUCTION: A STATISTICAL SURVEY OF THREE HUNDRED FORTY-TWO CASES. PMID- 17857140 TI - PERFORATED GASTRIC AND DUODENAL ULCER. PMID- 17857141 TI - MESENTERIC LYMPHADENITIS AND THE ACUTE ABDOMEN: REPORT OF THIRTEEN CASES. PMID- 17857143 TI - GENERALIZED LYMPHOGRANULOMA INGUINALE. PMID- 17857142 TI - THE PATHOGENESIS OF NECROSIS OF THE CEREBRAL GRAY MATTER FOLLOWING NITROUS OXIDE ANESTHESIA. PMID- 17857144 TI - PILONIDAL SINUS. PMID- 17857145 TI - PILONIDAL SINUS: OBSERVATIONS ON ONE HUNDRED FORTY CASES TREATED BY CAUTERY EXCISION. PMID- 17857146 TI - TREATMENT OF FRACTURES OF THE SHAFT OF THE FEMUR: AN ANALYSIS OF ONE HUNDRED TWENTY CASES. PMID- 17857147 TI - WATER BALANCE IN NEUROSURGICAL PATIENTS. PMID- 17857148 TI - SURGICAL KNOTS. PMID- 17857150 TI - MEMOIR: DUNCAN EVE 1853-1937. PMID- 17857149 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857151 TI - POSTANESTHETIC ENCEPHALOPATHY FOLLOWING CYCLOPROPANE. PMID- 17857152 TI - SEVERE DEGENERATION OF THE BRAIN FOLLOWING NITROUS OXIDE-OXYGEN ANESTHESIA. PMID- 17857153 TI - BRAIN ABSCESS OF UNDETERMINED ETIOLOGY: REPORT OF FOUR CASES WITH RECOVERY. PMID- 17857154 TI - TREATMENT OF HEMORRHAGE AND TRAUMATIC SHOCK BY THE INTRAVENOUS USE OF LYOPHILE SERUM. PMID- 17857155 TI - ACUTE APPENDICITIS IN COMPLETE TRANSPOSITION OF VISCERA: REPORT OF CASE WITH SYMPTOMS REFERABLE TO RIGHT SIDE MECHANISM OF PAIN IN VISCERAL DISEASE. PMID- 17857156 TI - THE BACTERIAL FLORA OF ACUTE PERFORATED APPENDICITIS WITH PERITONITIS: A BACTERIOLOGIC STUDY BASED UPON ONE HUNDRED CASES. PMID- 17857157 TI - THE RARE INCIDENCE OF ACUTE APPENDICITIS RESULTING FROM EXTERNAL TRAUMA. PMID- 17857158 TI - SURGICAL CONSIDERATION OF SOLITARY POLYPS OF THE COLON. PMID- 17857159 TI - RESULTS OF CONSERVATIVE TREATMENT OF ACUTE CHOLECYSTITIS. PMID- 17857160 TI - SPONTANEOUS POSTOPERATIVE RUPTURE OF THE BILE DUCTS. PMID- 17857162 TI - DIRECT INGUINAL HERNIA. PMID- 17857161 TI - DERMOID CYSTS OF THE MESENTERY. PMID- 17857163 TI - THE COMMUNICATING VEINS OF THE LOWER LEG AND THE OPERATIVE TECHNIC FOR THEIR LIGATION. PMID- 17857164 TI - INJURIES ABOUT THE SHOULDER JOINT IN CHILDREN, EXCLUSIVE OF FRACTURES OF THE CLAVICLE. PMID- 17857165 TI - STENOSING TENDOVAGINITIS AT THE RADIAL STYLOID PROCESS. PMID- 17857166 TI - THE BACTERIAL FLORA OF CLEAN SURGICAL WOUNDS. PMID- 17857167 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857168 TI - INTRODUCTORY ADDRESS. PMID- 17857169 TI - PRESIDENTIAL ADDRESS: MILESTONES ON THE ROAD OF SURGERY. PMID- 17857170 TI - INTRACRANIAL ANEURYSM OF THE INTERNAL CAROTID ARTERY: CURED BY OPERATION. PMID- 17857171 TI - ANEURYSMS OF THE CIRCLE OF WILLIS: A DISCUSSION OF DR. DANDY'S INTRACRANIAL OCCLUSION OF THE INTERNAL CAROTID FOR ANEURYSMS OF THE CIRCLE OF WILLIS, WITH SUPPLEMENTARY REMARKS. PMID- 17857173 TI - THE USE OF FASCIA AND RIBBON CATGUT IN THE REPAIR OF CLEFT PALATE AND HARELIP. PMID- 17857172 TI - BRAIN ABSCESS DUE TO GAS-FORMING, SPORE-BEARING ANAEROBES: REPORT OF TWO CASES, WITH RECOVERY. PMID- 17857174 TI - TRACHEO-ESOPHAGEAL FISTULA: DESCRIPTION OF A NEW OPERATIVE PROCEDURE AND CASE REPORT. PMID- 17857176 TI - CARCINOMA OF THE BREAST IN THE NEGRO. PMID- 17857175 TI - SCALENUS NEUROCIRCULATORY COMPRESSION. PMID- 17857177 TI - CARCINOMA OF THE BREAST. PMID- 17857178 TI - A SIMPLE TREATMENT FOR EMPYEMA IN CHILDREN. PMID- 17857179 TI - THOROCOPLASTY IN THE TREATMENT OF PULMONARY TUBERCULOSIS. PMID- 17857180 TI - LUNG ABSCESS: AN ANALYSIS OF THE CAUSES OF DEATH IN ONE HUNDRED CONSECUTIVE FATAL CASES. PMID- 17857181 TI - CARCINOMA OF THE STOMACH: WITH SPECIAL REFERENCE TO TOTAL GASTRECTOMY. PMID- 17857182 TI - DIVERTICULA OF THE JEJUNUM. PMID- 17857183 TI - THE COMPLICATING EFFECTS OF DIVERTICULITIS OF THE COLON UPON ABDOMINAL SURGERY AND ESPECIALLY UPON SURGERY OF THE LARGE BOWEL. PMID- 17857184 TI - THE SURGICAL TREATMENT OF INTRACTABLE, CHRONIC ULCERATIVE COLITIS. PMID- 17857185 TI - THE RETROPERITONEAL (RETROCOLIC) APPENDIX. PMID- 17857187 TI - PTOSED SPLEEN WITH TORSION OF PEDICLE. PMID- 17857186 TI - UNILOCULAR CYST OF LIVER. PMID- 17857188 TI - A COMPARISON OF THE THREE TYPES OF HYSTERECTOMY. PMID- 17857189 TI - A SIMPLE METHOD OF CONSTRUCTING A VAGINA: REPORT OF FOUR CASES. PMID- 17857190 TI - POSTERIOR VAGINAL HERNIA. PMID- 17857191 TI - VAGINAL CYSTS: WITH SPECIAL REFERENCE TO THOSE OF GARTNER'S DUCT. PMID- 17857192 TI - WILLIAM HALL GOODWIN 1882-1937. PMID- 17857193 TI - JAMES KNOX SIMPSON 1886-1937. PMID- 17857195 TI - NATHAN WINSLOW 1878-1937. PMID- 17857194 TI - JAMES ERNEST STOKES 1868-1937. PMID- 17857196 TI - UVEOPAROTITIS. PMID- 17857197 TI - SPIVACK'S GASTROSTOMY: AN ANALYSIS OF THIRTEEN CASES WITH A REVIEW OF THE TECHNIC. PMID- 17857198 TI - ENDOMETRIOSIS OF THE RECTUM AND SIGMOID: REVIEW OF THE LITERATURE AND CASE REPORT. PMID- 17857199 TI - EARLY CARDIAC DECOMPENSATION IN TRAUMATIC ARTERIOVENOUS ANEURYSMS. PMID- 17857200 TI - MEMOIR: DANIEL FISKE JONES 1868-1937. PMID- 17857201 TI - ADRENAL CORTICAL TUMORS AND THEIR TREATMENT: A STUDY OF SEVEN OPERATED CASES. PMID- 17857202 TI - THE SURGICAL PROBLEM OF HYPERTENSION. PMID- 17857203 TI - THE CLINICAL RESULTS OF CELIAC GANGLIONECTOMY IN THE TREATMENT OF ESSENTIAL HYPERTENSION. PMID- 17857205 TI - DIVERTICULUM OF THE FEMALE URETHRA. PMID- 17857204 TI - THE ADVANTAGES OF THE ABDOMINAL APPROACH TO INGUINAL HERNIA. PMID- 17857206 TI - THE MODERN TREATMENT OF VARICOSE VEINS AS INDICATED BY THE COMPARATIVE TOURNIQUET TEST. PMID- 17857207 TI - THE REPAIR OF SURFACE DEFECTS OF THE HAND. PMID- 17857208 TI - THE INFLUENCE OF PREOPERATIVE MEDICATION ON POSTOPERATIVE COMPLICATIONS: A STATISTICAL STUDY. PMID- 17857209 TI - INTERNAL FIXATION OF FRACTURES OF THE NECK OF THE FEMUR: AN ANALYSIS OF RESULTS. PMID- 17857210 TI - LUMBOSACRAL AND SACRO-ILIAC STRAIN CAUSING LOW BACK PAIN: A REVIEW OF ONE HUNDRED FIFTY CASES. PMID- 17857211 TI - GLASS RODS AND OTHER ITEMS IN THE TECHNIC OF THE ABDOMINAL INCISION. PMID- 17857213 TI - POSTOPERATIVE JEJUNAL ULCER: A STUDY OF TWENTY-THREE CASES OPERATED UPON AT THE PRESBYTERIAN HOSPITAL, NEW YORK. PMID- 17857212 TI - THE INSENSIBLE LOSS IN SURGICAL PATIENTS. PMID- 17857214 TI - FUSION IN CHARCOT'S DISEASE OF THE KNEE: A NEW TECHNIC FOR ARTHRODESIS. PMID- 17857215 TI - INTRAMEDULLARY PRESSURE WITH PARTICULAR REFERENCE TO MASSIVE DIAPHYSEAL BONE NECROSIS: EXPERIMENTAL OBSERVATIONS. PMID- 17857216 TI - THE EFFECT OF THE DIRECT APPLICATION OF COD LIVER OIL UPON THE HEALING OF ULCERS OF THE FEET IN PATIENTS WITH DIABETES MELLITUS. PMID- 17857217 TI - EXCISION OF THE AXILLARY VEIN IN THE RADICAL OPERATION FOR CARCINOMA OF THE BREAST. PMID- 17857218 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857219 TI - POSTOPERATIVE ROENTGENOTHERAPY IN CANCER OF THE BREAST. PMID- 17857220 TI - PEPTIC ULCER. PMID- 17857221 TI - CHANGING METHODS IN THE SURGICAL TREATMENT OF PEPTIC ULCER: A STUDY OF THE CASES OPERATED UPON AT THE ROOSEVELT HOSPITAL, NEW YORK. PMID- 17857222 TI - GASTRO-ENTEROSTOMY. PMID- 17857223 TI - ALLEN B. KANAVEL 1874-1938. PMID- 17857224 TI - THE USE OF HEPARIN IN THROMBOSIS. PMID- 17857226 TI - THE OPERATIVE TREATMENT OF COMMUNICATING HYDROCEPHALUS. PMID- 17857225 TI - A STUDY OF EXPERIMENTAL AND CLINICAL SHOCK WITH SPECIAL REFERENCE TO ITS TREATMENT BY THE INTRAVENOUS INJECTION OF PRESERVED PLASMA. PMID- 17857228 TI - SURGICAL ASPECTS OF LESIONS OF MECKEL'S DIVERTICULUM. PMID- 17857227 TI - PRIMARY MALIGNANCY OF THE JEJUNUM AND ILEUM. PMID- 17857229 TI - TRAUMATIC RUPTURE OF THE BILE DUCTS. PMID- 17857230 TI - THE CLINICAL SIGNIFICANCE OF PANCREATIC REFLUX. PMID- 17857232 TI - PRIMARY CARCINOMA OF THE URETER. PMID- 17857231 TI - STUDIES ON RENAL HYPERTENSION: THE EFFECT OF DEVIATING URINE INTO THE BLOOD STREAM AND INTESTINES OF DOGS. PMID- 17857233 TI - THE FATE OF TENDON, FASCIA AND ELASTIC CONNECTIVE TISSUE TRANSPLANTED INTO BONE. PMID- 17857234 TI - AN EVALUATION OF EXCISION IN THE TREATMENT OF UNUNITED FRACTURE OF THE CARPAL SCAPHOID (NAVICULAR) BONE. PMID- 17857236 TI - SUBLINGUAL EPIDERMOID CYSTS. PMID- 17857235 TI - THE OSSEOUS SYSTEM IN HODGKIN'S DISEASE. PMID- 17857238 TI - GELATINOUS MAMMARY CANCER. PMID- 17857237 TI - THE REGENERATION OF SENSATION IN TRANSPLANTED SKIN. PMID- 17857239 TI - THE DIFFERENTIAL DIAGNOSIS OF HYPERPARATHYROIDISM: WITH SPECIAL REFERENCE TO POLYOSTOTIC FIBROUS DYSPLASIA. PMID- 17857240 TI - THE TREATMENT OF POSTOPERATIVE TETANY WITH DIHYDROTACHYSTEROL. PMID- 17857242 TI - DIRECT INGUINAL HERNIA: PRESENTATION OF AN OPERATION FOR ITS CURE. PMID- 17857241 TI - CONGENITAL DIAPHRAGMATIC HERNIA. PMID- 17857243 TI - MADELUNG'S DEFORMITY. PMID- 17857245 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857244 TI - INTRACAPSULAR FRACTURES OF THE NECK OF THE FEMUR: A STUDY OF ONE HUNDRED NINETY CASES. PMID- 17857246 TI - MEMOIR: EDWARD MARTIN 1859-1938. PMID- 17857248 TI - THE NEED OF A NATIONAL COUNCIL ON MEDICAL EDUCATION, LICENSURE, AND HOSPITALS. PMID- 17857247 TI - ADDRESS OF THE PRESIDENT: THE RELATION OF SURGEON AND HOSPITAL. PMID- 17857249 TI - THE TREATMENT OF CRANIAL OSTEOMYELITIS AND BRAIN. PMID- 17857250 TI - RAPID CONTROL OF INTRACRANIAL PRESSURE. PMID- 17857251 TI - PROGRESSIVE EXOPHTHALMOS ASSOCIATED WITH DISORDERS OF THE THYROID GLAND. PMID- 17857252 TI - INJURIES TO THE RECURRENT LARYNGEAL NERVE IN THYROID OPERATIONS: THEIR MANAGEMENT AND AVOIDANCE. PMID- 17857253 TI - AMOUNT OF THYROID TISSUE TO BE LEFT IN OPERATIONS FOR DIFFUSE TOXIC GOITER. PMID- 17857254 TI - THE IODINE METABOLISM IN EXOPHTHALMIC GOITER. PMID- 17857255 TI - MEDIASTINITIS FOLLOWING CERVICAL SUPPURATION. PMID- 17857256 TI - THE MANAGEMENT OF CERTAIN LESIONS OF THE ESOPHAGUS. PMID- 17857257 TI - LYMPHATIC SPREAD OF CARCINOMA OF THE RECTUM. PMID- 17857258 TI - ARTERIOVENOUS ANEURYSMS. PMID- 17857259 TI - SPONTANEOUS ARTERIOVENOUS FISTULA BETWEEN THE ABDOMINAL AORTA AND THE INFERIOR VENA CAVA: CASE REPORT PRESENTED IN DISCUSSION OF THE PAPER BY DOCTORS REID AND MCGUIRE ON ARTERIOVENOUS ANEURYSMS. PMID- 17857260 TI - CONGENITAL ARTERIOVENOUS FISTULA OR FISTULAE: CASE REPORT PRESENTED, BY TITLE, IN DISCUSSION OF THE PAPER BY DOCTORS REID AND MCGUIRE ON ARTERIOVENOUS ANEURYSMS. PMID- 17857261 TI - HEMINEPHRECTOMY IN DISEASE OF THE DOUBLE KIDNEY: REPORT OF FOURTEEN CASES. PMID- 17857262 TI - DENERVATION OF THE BLADDER FOR RELIEF OF INTRACTABLE PAIN. PMID- 17857263 TI - THE REPAIR OF ABDOMINAL INCISIONS. PMID- 17857264 TI - SPONTANEOUS RUPTURE OF THE SUPERIOR AND INFERIOR EPIGASTRIC ARTERIES WITHIN THE RECTUS ABDOMINIS SHEATH. PMID- 17857265 TI - THE REPLACEMENT OF SODIUM CHLORIDE IN SURGICAL PATIENTS. PMID- 17857266 TI - ACUTE CHOLECYSTITIS IN A BACILLUS TYPHOSUS CARRIER: CHOLECYSTOSTOMY CHOLECYSTECTOMY-CHOLEDOCHOTOMY. PMID- 17857267 TI - JOHN JENKINS BUCHANAN 1855-1937. PMID- 17857269 TI - JOSEPH AUGUSTUS BLAKE 1864-1937. PMID- 17857268 TI - ALLEN BUCKNER KANAVEL 1874-1938. PMID- 17857270 TI - ROBERT BATTEY GREENOUGH 1871-1937. PMID- 17857271 TI - OBSERVATIONS ON THE MODE OF ACTION OF SULFANILAMIDE AND ITS APPLICATION TO SURGICAL INFECTIONS. PMID- 17857272 TI - TOXIC MANIFESTATIONS OF SULFANILAMIDE. PMID- 17857273 TI - THE EFFECT OF SULFANILAMIDE UPON HUMAN, VIRULENT HEMOLYTIC STREPTOCOCCI. PMID- 17857274 TI - TREATMENT OF HEMATOGENOUS NEPHRITIS WITH SULFANILAMIDE: CASE REPORT. PMID- 17857275 TI - THE TREATMENT OF INTRAPERITONEAL ABSCESS ARISING FROM APPENDICITIS. PMID- 17857276 TI - REGIONAL ENTERITIS. PMID- 17857277 TI - PERIANAL FISTULAE AS A COMPLICATION OF REGIONAL ILEITIS. PMID- 17857279 TI - EPIDERMOID CYSTS OF THE SPLEEN. PMID- 17857278 TI - ACUTE CHOLECYSTITIS: THE RESULTS OF OPERATION WITHIN FORTY-EIGHT HOURS OF THE ONSET OF SYMPTOMS. PMID- 17857280 TI - EMBRYOMA OF THE KIDNEY (WILMS' TUMOR). PMID- 17857281 TI - THERAPEUTIC MANAGEMENT OF URINARY INFECTIONS. PMID- 17857282 TI - THYMOL THERAPY IN ACTINOMYCOSIS. PMID- 17857283 TI - THE PROBLEM OF WOUND HEALING: THE EFFECT OF LOCAL ANTISEPTIC AGENTS ON INFECTED WOUNDS. PMID- 17857284 TI - THE EFFECT OF URINARY BLADDER TRANSPLANTS AND EXTRACTS ON THE FORMATION OF BONE: A FURTHER EXPERIMENTAL STUDY. PMID- 17857285 TI - THE APPARENT ALTERATION OF TETANUS TOXIN WITHIN THE SPINAL CORD OF DOGS. PMID- 17857286 TI - TOXIC MYELOPATHY (SPINOCAINE): SOME CONTRAINDICATIONS TO SPINOCAINE ANESTHESIA. PMID- 17857287 TI - THE EFFECT OF BREATHING 95 PER CENT OXYGEN UPON THE INTRALUMINAL PRESSURE OCCASIONED BY GASEOUS DISTENTION OF THE OBSTRUCTED SMALL INTESTINE. PMID- 17857288 TI - IMPORTANT STEPS IN ASEPTIC INTESTINAL ANASTOMOSIS. PMID- 17857289 TI - TRANSIENT ACUTE PANCREATITIS. PMID- 17857290 TI - SURGERY AND DIABETES. PMID- 17857291 TI - STRANGULATED LITTRE'S FEMORAL HERNIA WITH SPONTANEOUS FECAL FISTULA: CASE REPORT WITH A REVIEW OF THE LITERATURE. PMID- 17857292 TI - THE PERINEAL TESTIS. PMID- 17857293 TI - EFFECTS OF LIGATIONS ON NERVES OF THE EXTREMITIES. PMID- 17857294 TI - ACUTE HEMATOGENOUS BURSITIS. PMID- 17857296 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857295 TI - CHROMICIZED BEEF TENDON FOR INTERNAL FIXATION OF FRACTURES. PMID- 17857297 TI - THE TREATMENT OF BRAIN ABSCESS. PMID- 17857299 TI - EPIDURAL SPINAL INFECTIONS. PMID- 17857298 TI - CARCINOMATOUS METASTASES TO THE BRAIN. PMID- 17857300 TI - LIGATURE OF THE COMMON CAROTID ARTERY IN CANCER OF THE HEAD AND NECK. PMID- 17857301 TI - THE EFFICACY OF "COLEY'S TOXIN" IN THE TREATMENT OF SARCOMA: AN EXPERIMENTAL STUDY. PMID- 17857302 TI - MULTIPLE DENTIGEROUS CYSTS: WITH SPECIAL REFERENCE TO OCCURRENCE IN SIBLINGS. PMID- 17857303 TI - PULSATING, BENIGN GIANT CELL TUMORS OF BONE. PMID- 17857304 TI - THE TREATMENT OF DELAYED UNION AND NONUNION OF FRACTURES BY SUBCUTANEOUS DRILLING. PMID- 17857305 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857307 TI - SPINAL SUBARACHNOID INJECTION OF ABSOLUTE ALCOHOL FOR THE RELIEF OF INTRACTABLE PAIN. PMID- 17857306 TI - THE LOCALIZATION OF INTRACRANIAL LESIONS: THE DETERMINATION OF AREAS OF HYPERPATHIA OF THE SCALP. PMID- 17857308 TI - RECURRING PERITONITIS FOLLOWING OPERATIVE REDUCTION OF A STRANGULATED INGUINAL HERNIA: CURE FOLLOWING RESECTION OF THE DAMAGED LOOP. PMID- 17857309 TI - NONROTATION OF THE INTESTINE. PMID- 17857310 TI - INTRA-ABDOMINAL OMENTAL TORSION: REPORT OF THREE CASES. PMID- 17857311 TI - SPLENECTOMY IN VARIOUS BLOOD DISORDERS. PMID- 17857312 TI - A METHOD FOR TRANSPLANTING THE ADRENAL GLAND OF THE DOG WITH REESTABLISHMENT OF ITS BLOOD SUPPLY: REPORT OF OBSERVATIONS. PMID- 17857313 TI - RENAL CARBUNCLE: CASE REPORT AND COMPARATIVE REVIEW. PMID- 17857314 TI - VARIATION IN THE CHOLESTEROL, BILE PIGMENT AND CALCIUM SALTS CONTENTS OF GALLSTONES FORMED IN GALLBLADDER AND IN BILE DUCTS WITH THE DEGREE OF ASSOCIATED OBSTRUCTION. PMID- 17857315 TI - FURTHER EVIDENCE THAT PANCREATIC JUICE REFLUX MAY BE ETIOLOGIC FACTOR IN GALLBLADDER DISEASE. PMID- 17857316 TI - A STUDY OF THE RESULTS OF SURGICAL TREATMENT OF PEPTIC ULCER. PMID- 17857317 TI - CARCINOMA OF THE PERIPAPILLARY PORTION OF THE DUODENUM. PMID- 17857318 TI - NEUROFIBROSARCOMA OF THE SMALL BOWEL: REPORT OF TWO CASES. PMID- 17857319 TI - DILATATION OF THE COLON: REPORT OF A CASE FOLLOWING THE DEVELOPMENT OF AN AORTIC ANEURYSM; RELIEVED BY DILATATION OF THE ANAL SPHINCTERS. PMID- 17857320 TI - CELIAC GANGLIONECTOMY AND PLEXUS RESECTION FOR TABETIC GASTRIC CRISES. PMID- 17857321 TI - BILATERAL AND UNILATERAL RENAL AGENESIS. PMID- 17857322 TI - DERMOID CYST OF THE BLADDER: CASE REPORT. PMID- 17857323 TI - CYSTS OF THE URACHUS: REPORT OF TWO CASES. PMID- 17857324 TI - WHOLE-THICKNESS GRAFTS IN CORRECTION OF CONTRACTURES DUE TO BURN SCARS: THREE CASE REPORTS. PMID- 17857325 TI - PILONIDAL SINUS: SACROCOCCYGEAL ECTODERMAL CYSTS AND SINUSES. PMID- 17857327 TI - THE EFFECT OF CONSTANT GASTRIC SUCTION ON THE ACID-BASE EQUILIBRIUM OF THE BODY. PMID- 17857326 TI - GAS GANGRENE FOLLOWING THERAPEUTIC INJECTIONS. PMID- 17857328 TI - MEMOIR: FREDERIC JAY COTTON 1869-1938. PMID- 17857329 TI - TO THE EDITORS OF THE ANNALS OF SURGERY. PMID- 17857330 TI - SOME RECENT ADVANCES IN SURGICAL THERAPEUSIS. PMID- 17857331 TI - SURGERY OF THE GALLBLADDER. PMID- 17857332 TI - HEPATIC AND BILIARY TRACT DISEASE: A REVIEW OF RECENT SIGNIFICANT ADVANCES. PMID- 17857333 TI - LARGE, CAVERNOUS HEMANGIOMATA OF THE LIVER: REPORT OF AN INOPERABLE CASE TREATED WITH ROENTGENOTHERAPY. PMID- 17857335 TI - SURGICAL PROCEDURES FOR CARCINOMA OF THE TRANSVERSE COLON. PMID- 17857334 TI - CARCINOMA OF THE PERIPAPILLARY PORTION OF THE DUODENUM. PMID- 17857336 TI - SHORT INTERVAL, TWO STAGE THYROID LOBECTOMY FOR HYPERTHYROIDISM. PMID- 17857337 TI - SECONDARY DEFORMITIES IN CLEFT PALATE PATIENTS. PMID- 17857338 TI - PERFORATED WOUND OF THE RECTUM INTO THE POUCH OF DOUGLAS: CAUSED BY IMPALEMENT. PMID- 17857339 TI - A TECHNIC FOR PRODUCING FACIAL MASKS AND MODELS. PMID- 17857340 TI - SEGMENTAL PNEUMONECTOMY IN BRONCHIECTASIS: THE LINGULA SEGMENT OF THE LEFT UPPER LOBE. PMID- 17857341 TI - THE GRADING AND PROGNOSIS OF CARCINOMA OF THE COLON AND RECTUM. PMID- 17857343 TI - MIXED TUMORS OF THE SUBLINGUAL GLAND. PMID- 17857342 TI - MALIGNANT TUMORS OF THE SALIVARY GLANDS. PMID- 17857344 TI - ESOPHAGOGASTROSTOMY FOR CARCINOMA OF THE ESOPHAGUS. PMID- 17857346 TI - MORBIDITY FOLLOWING CHOLECYSTECTOMY. PMID- 17857345 TI - DUODENAL STASIS: CLINICAL AND EXPERIMENTAL OBSERVATIONS. PMID- 17857347 TI - PROTHROMBIN DEFICIENCY AND THE EFFECTS OF VITAMIN K IN OBSTRUCTIVE JAUNDICE AND BILIARY FISTULA. PMID- 17857348 TI - ACUTE HEMATOGENOUS OSTEOMYELITIS OF THE LONG BONES: A CLINICAL REVIEW OF 160 CASES. PMID- 17857349 TI - CYSTIC DISEASE OF THE SPLEEN. PMID- 17857350 TI - RHABDOMYOSARCOMA OF THE URINARY BLADDER. PMID- 17857352 TI - PRESIDENTIAL ADDRESS: THE PANAMA ADVENTURE. PMID- 17857351 TI - FURTHER OBSERVATIONS ON BENIGN TUMORS OF THE TENDON SHEATH. PMID- 17857353 TI - EXTRADURAL DIPLOIC AND INTRADURAL EPIDERMOID TUMORS (CHOLESTEATOMA). PMID- 17857354 TI - THE TREATMENT OF INTERNAL CAROTID ANEURYSMS WITHIN THE CAVERNOUS SINUS AND THE CRANIAL CHAMBER: REPORT OF THREE CASES. PMID- 17857355 TI - THYROTOXICOSIS: INCLUDING A STUDY OF THE DURATION OF PREOPERATIVE TREATMENT. PMID- 17857356 TI - RESULTS OF THYROIDECTOMY IN HYPERTHYROIDISM ASSOCIATED WITH NEUROCIRCULATORY ASTHENIA. PMID- 17857357 TI - TRAUMATIC ARTERIOVENOUS ANEURYSMS OF THE GREAT VESSELS OF THE NECK: OBSERVATIONS UPON SEVEN CASES. PMID- 17857359 TI - SUPPURATIVE PERICARDITIS. PMID- 17857358 TI - ARTERIOVENOUS ANEURYSM (FEMORAL BELOW PROFUNDA): CASE REPORT. PMID- 17857360 TI - TREATMENT OF PEPTIC ULCER. PMID- 17857361 TI - PRIMARY CARCINOMA OF THE ILEUM. PMID- 17857362 TI - MEGARECTUM AND MEGASIGMOID. PMID- 17857363 TI - SURGICAL TREATMENT OF COMPLETE RECTAL PROLAPSE. PMID- 17857364 TI - PANCREATIC CALCULI: A REVIEW OF SIXTY-FIVE OPERATIVE AND ONE HUNDRED THIRTY-NINE NON-OPERATIVE CASES. PMID- 17857366 TI - THE RELATION OF CHRONIC INFLAMMATION AND ESPECIALLY LYMPHOGRANULOMA INGUINALE TO THE DEVELOPMENT OF SQUAMOUS CELL CARCINOMA OF THE RECTUM. PMID- 17857365 TI - MESENTERIC LYMPHADENITIS. PMID- 17857367 TI - INTESTINAL OBSTRUCTION DUE TO INTRALUMINAL FOREIGN BODIES. PMID- 17857368 TI - TRICHOBEZOARS: REPORT OF A CASE WITH RECURRENCE. PMID- 17857369 TI - SURGERY IN HEMOPHILIA: REPORT OF FOUR CASES. PMID- 17857370 TI - THE THEORY AND PRACTICAL USE OF THE Z-INCISION FOR THE RELIEF OF SCAR CONTRACTURES. PMID- 17857371 TI - THE UTILIZATION OF THE TEMPORAL MUSCLE AND FASCIA IN FACIAL PARALYSIS. PMID- 17857372 TI - TREATMENT OF SCIATIC SYNDROME BY ILIOTIBIAL FASCIAL BAND SECTION. PMID- 17857373 TI - NEUROLOGIC ASPECTS OF LOW BACK PAIN AND SCIATICA. PMID- 17857374 TI - A CLAMP FOR CLOSURE OF THE DUODENAL STUMP IN GASTRIC RESECTIONS: A MODIFICATION OF THE FURNISS CLAMP. PMID- 17857375 TI - EDMUND DOUGAN CLARK 1869-1938. PMID- 17857376 TI - FRANK S. LYNN 1884-1938. PMID- 17857377 TI - THE ANTISEPTIC AND DETOXIFYING ACTION OF ZINC PEROXIDE ON CERTAIN SURGICAL AEROBIC, ANAEROBIC AND MICRO-AEROPHILIC BACTERIA. PMID- 17857378 TI - BENIGN AND MALIGNANT LESIONS OF THE MALE BREAST. PMID- 17857380 TI - NONPENETRATING INTRA-ABDOMINAL INJURY. PMID- 17857379 TI - PLASMA CELL MASTITIS. PMID- 17857381 TI - STUDIES ON THE REACTION OF THE PERITONEUM TO TRAUMA AND INFECTION. PMID- 17857383 TI - UNUSUAL SPLEEN CASES. PMID- 17857382 TI - APPENDICOCECOSTOMY IN THE TREATMENT OF PERITONITIS. PMID- 17857384 TI - CONSERVATIVE PELVIC SURGERY. PMID- 17857386 TI - INJURY TO URETERS DURING PELVIC OPERATIONS. PMID- 17857385 TI - GENITAL TUBERCULOSIS AND PREGNANCY: WITH SPECIAL REFERENCE TO TUBAL GESTATION. PMID- 17857387 TI - FEMORAL HERNIA: REPORT OF NINETY OPERATIONS. PMID- 17857388 TI - The Surgery of the Spine. PMID- 17857389 TI - Drainage in the Treatment of Certain Injuries and Diseases involving the Floor of the Cranium. PMID- 17857391 TI - Notes on Surgical Questions Discussed at the Paris Congress on Tuberculosis. PMID- 17857390 TI - The Presence of Spinal Distortion in the Early Stage of Spondylitis and its Value as a Diagnostic Sign. PMID- 17857392 TI - On the Diagnosis of Pancreatic Disease in its Bearing on the Surgery of the Liver. PMID- 17857393 TI - Studies in Actinomycosis. PMID- 17857394 TI - INDEX OF SURGICAL PROGRESS. PMID- 17857396 TI - Abscess of Brain Consecutive to a Fracture of the Skull. PMID- 17857395 TI - Free Division of the Capsule of the Kidney for the Relief of Nephralgia. PMID- 17857397 TI - On the Principles of Treatment of Suppuration in Cavities with Rigid Walls, with Special Regard to Empyema of the Pleura. PMID- 17857398 TI - INDEX OF SURGICAL PROGRESS. PMID- 17857399 TI - A Note on Dermoid Cysts of the Scalp and Mid-Line of the Back. PMID- 17857400 TI - Acute Infectious Osteomyelitis and Periostitis. PMID- 17857402 TI - The Questions of the Antitubercular Power of Iodoform. PMID- 17857401 TI - On Osteomata of the Nasal Cavity. PMID- 17857404 TI - Primary Cancer of the Extremities. PMID- 17857403 TI - Double Consecutive Castration for Primary Tuberculosis of Testicles. PMID- 17857405 TI - Suprapubic Lithotomy in Russia. PMID- 17857406 TI - INDEX OF SURGICAL PROGRESS. PMID- 17857407 TI - Cholecystotomy by Lumbar Incision for Distended Gall-Bladder Simulating Floating Kidney. PMID- 17857408 TI - Two Cases of Cervical Adenomata with Unusually Extensive Dissection of the Tissues of the Neck. PMID- 17857409 TI - The Etiology and Diagnosis of Malignant Tumors, Especially those of the Tongue and Lips. PMID- 17857410 TI - INDEX OF SURGICAL PROGRESS. PMID- 17857412 TI - Perinectomy. PMID- 17857411 TI - The Cure of Hemorrhoids by Excision and Closure with the Buried Animal Suture. PMID- 17857413 TI - Nephro-Lithotomy. PMID- 17857414 TI - Note upon a Resource after Failure of Hernia Operations. PMID- 17857415 TI - Landerer's Dry Method of Operating. PMID- 17857417 TI - Senn on the Healing of Aseptic Bone Cavities by Implantation of Antiseptic Decalcified Bone. PMID- 17857416 TI - Staffel on the Surgical Treatment of Intestinal Stricture and Occlusion. PMID- 17857418 TI - INDEX OF SURGICAL PROGRESS. PMID- 17857419 TI - Erasion of Arthrectomy of the Knee-Joint. PMID- 17857420 TI - Bony Anchylosis of Temporo-Maxillary Joint Relieved by Osteotomy of the Neck of the Inferior Maxilla. PMID- 17857421 TI - The Treatment of Appendicitis by Early Laparotomy. PMID- 17857422 TI - The Aseptic Appliances at the Hotel Dieu of Lyons. PMID- 17857423 TI - INDEX OF SURGICAL PROGRESS. PMID- 17857424 TI - CARCINOMA OF THE COLON AND RECTUM: DEDUCTIONS FROM EIGHT HUNDRED OPERATIONS. PMID- 17857425 TI - GAS GANGRENE. PMID- 17857426 TI - FRACTURES AND DISLOCATIONS BY MUSCULAR VIOLENCE, COMPLICATING CONVULISONS INDUCED BY METRAZOL FOR SCHIZOPHRENIA. PMID- 17857428 TI - BRIEF COMMUNICATIONS. PMID- 17857427 TI - THE USE OF VITALLIUM AS A MATERIAL FOR INTERNAL FIXATION OF FRACTURES. PMID- 17857429 TI - TECHNIC AND DEMONSTRABLE ADVANTAGES OF THE DEVINE COLOSTOMY. PMID- 17857430 TI - FRANCIS REDER 1864-1936. PMID- 17857431 TI - JOHN ROBERTS CAULK 1881-1938. PMID- 17857432 TI - JOHN HENRY NEFF, JR. 1887-1938. PMID- 17857433 TI - ELLIS FISCHEL 1883-1938. PMID- 17857434 TI - THE SAMUEL D. GROSS PRIZE: FIFTEEN HUNDRED DOLLARS. PMID- 17857435 TI - THE EFFECT OF ACUTE INTESTINAL OBSTRUCTION ON THE BLOOD AND PLASMA VOLUMES. PMID- 17857437 TI - INTERNAL BILIARY FISTULAE AND INTESTINAL OBSTRUCTIONS DUE TO GALLSTONES. PMID- 17857436 TI - A STUDY OF THE RESULTS OF MEDICAL TREATMENT OF DUODENAL ULCER. PMID- 17857438 TI - CHOLEDOCHUS CYST WITH A DOUBLE COMMON BILE DUCT: SEQUELAE AND COMPLICATIONS. PMID- 17857439 TI - DOUBLE GALLBLADDER WITH TWO CYSTIC DUCTS AND TWO CYSTIC ARTERIES. PMID- 17857440 TI - THE EFFECT OF DEHYDROCHOLIC ACID UPON BILIARY PRESSURE AND ITS CLINICAL APPLICATION. PMID- 17857441 TI - HABITUAL DISLOCATION OF THE DIGITAL EXTENSOR TENDONS. PMID- 17857442 TI - STUDIES OF CYCLOPROPANE-THE USE OF BARBITURATES IN PREVENTING CARDIAC IRREGULARITIES UNDER CYCLOPROPANE OR MORPHINE AND CYCLOPROPANE ANESTHESIA: AN EXPERIMENTAL STUDY. PMID- 17857443 TI - THE APPLICATION OF CARBAMIDE (UREA) THERAPY IN WOUND HEALING. PMID- 17857444 TI - PAPILLEDEMA WITHOUT INTRACRANIAL PRESSURE (OPTIC NEURITIS). PMID- 17857445 TI - HURTHLE CELL TUMORS OF THE THYROID. PMID- 17857446 TI - RETROPHARYNGEAL AND LATERAL PHARYNGEAL ABSCESSES: AN ANATOMIC AND CLINICAL STUDY. PMID- 17857447 TI - PRIMARY LYMPHOSARCOMA OF THE STOMACH. PMID- 17857448 TI - PRIMARY CLOSURE OF PERITONEUM IN ACUTE APPENDICITIS WITH PERFORATION: REPORT OF TWENTY CASES. PMID- 17857449 TI - CONGENITAL CYSTIC KIDNEY TREATED BY URETERAL DRAINAGE. PMID- 17857450 TI - EARLY RECOGNITION OF SHOCK AND ITS DIFFERENTIATION FROM HEMORRHAGE. PMID- 17857452 TI - SPINAL EXTRADURAL CYST ASSOCIATED WITH KYPHOSIS DORSALIS JUVENILIS. PMID- 17857451 TI - DERMOID CYSTS OF THE VERTEBRAL CANAL. PMID- 17857453 TI - POSTOPERATIVE TEMPERATURE REACTIONS: REDUCTIONS OBTAINED BY STERILIZING THE AIR WITH BACTERICIDAL RADIANT ENERGY: SEASONAL VARIATIONS. PMID- 17857454 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857455 TI - SURGICAL MANAGEMENT OF THE PATENT DUCTUS ARTERIOSUS: WITH SUMMARY OF FOUR SURGICALLY TREATED CASES. PMID- 17857456 TI - A REVALUATION OF THE TREATMENT OF HEAD INJURIES. PMID- 17857457 TI - MASSIVE HEMORRHAGE IN PEPTIC ULCER: THE TRANSFUSION TEST FOR DETERMINING THE NECESSITY OF OPERATION. PMID- 17857458 TI - THE VALUE OF CECOSTOMY AS A COMPLEMENTARY AND DECOMPRESSIVE OPERATION. PMID- 17857459 TI - RETROPERITONEAL CHYLE CYSTS: WITH ESPECIAL REFERENCE TO THE LYMPHANGIOMATA. PMID- 17857460 TI - THE ROLE OF THE NERVOUS SYSTEM IN ACUTE INTESTINAL OBSTRUCTION: AN EXPERIMENTAL INVESTIGATION. PMID- 17857461 TI - THE TREATMENT OF VOLKMANN'S ISCHEMIC CONTRACTURE. PMID- 17857463 TI - AN OPERATION FOR THE CURE OF FLATFOOT. PMID- 17857462 TI - SOLITARY MYELOMA OF BONE: A CLINICAL AND PATHOLOGIC ENTITY. PMID- 17857465 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857464 TI - THE TREATMENT OF ANKLE MALUNION: A STUDY OF END-RESULTS. PMID- 17857466 TI - ADDRESS OF THE PRESIDENT: THE DEVELOPMENT OF NATIONAL SURGICAL SOCIETIES WITH THE ADVENT OF MODERN SURGERY. PMID- 17857467 TI - REPAIR OF CRANIAL DEFECTS BY CRANIOPLASTY. PMID- 17857468 TI - EXPERIENCES WITH THE TOTAL AND INTRACAPSULAR EXTIRPATION OF ACOUSTIC NEUROMATA. PMID- 17857469 TI - INTRACRANIAL ARTERIOVENOUS ANEURYSMS. PMID- 17857470 TI - MYASTHENIA GRAVIS AND TUMORS OF THE THYMIC REGION: REPORT OF A CASE IN WHICH THE TUMOR WAS REMOVED. PMID- 17857471 TI - LEFT SUBPHRENIC ABSCESS. PMID- 17857472 TI - EXTRAPLEURAL PNEUMOTHORAX. PMID- 17857473 TI - BOWEL OBSTRUCTION IN THE NEW BORN. PMID- 17857474 TI - PEPTIC ULCERS PERFORATING INTO THE PANCREAS. PMID- 17857475 TI - LATERAL GASTRODUODENOSTOMY IN CERTAIN CASES OF DUODENAL AND RECURRING ULCER. PMID- 17857476 TI - EXPERIMENTAL PROOF OF THE OBSTRUCTIVE ORIGIN OF APPENDICITIS IN MAN. PMID- 17857477 TI - ILEOCOLOSTOMY WITH EXCLUSION. PMID- 17857478 TI - THE VALUE OF PRELIMINARY COLOSTOMY IN THE CORRECTION OF GASTROJEJUNOCOLIC FISTULA. PMID- 17857479 TI - SCLEROSING OR RETRACTILE MESENTERITIS: ITS TREATMENT AND THAT OF ADHESIONS WITH THE ELECTROSURGICAL KNIFE. PMID- 17857480 TI - LIVER TRAUMA AND THE HEPATORENAL SYNDROME. PMID- 17857481 TI - CONTROL OF POSTOPERATIVE BLEEDING IN OBSTRUCTIVE JAUNDICE. PMID- 17857483 TI - GANGRENE OF THE EXTREMITY IN THE DIABETIC. PMID- 17857482 TI - THE SIGNIFICANCE OF THE CHOLESTEROL PARTITION OF THE BLOOD SERUM IN SURGERY OF THE GALLBLADDER. PMID- 17857484 TI - FIBROMA OF THE OVARY WITH ASCITES AND HYDROTHORAX: A FURTHER REPORT. PMID- 17857485 TI - THE EFFECT OF DISTENTION OF THE COLON AND STIMULATION OF ITS NERVE SUPPLY ON THE FLOW OF BILE FROM THE LIVER. PMID- 17857487 TI - EMMET RIXFORD 1865-1938. PMID- 17857486 TI - CIRCULATORY PROBLEMS OF SURGICAL IMPORTANCE IN THE DIAGNOSIS OF ABDOMINAL LESIONS. PMID- 17857488 TI - SIR THOMAS MYLES 1857-1937. PMID- 17857489 TI - JOHN LAWRENCE YATES 1872-1938. PMID- 17857490 TI - EDWIN BEER 1876-1938. PMID- 17857492 TI - THE INFLUENCE OF CERTAIN DRUGS AND ANESTHETICS UPON GASTRO-INTESTINAL TONE AND MOTILITY. PMID- 17857491 TI - FRANZ J. A. TOREK 1861-1938. PMID- 17857493 TI - THE ASSAY OF GENERAL ANESTHETIC AGENTS. PMID- 17857494 TI - TRENDS IN INHALATION ANESTHESIA. PMID- 17857496 TI - THE PRESENT STATUS OF SPINAL ANESTHESIA. PMID- 17857495 TI - ANOXIA: A SOURCE OF POSSIBLE COMPLICATIONS IN SURGICAL ANESTHESIA. PMID- 17857497 TI - SPINAL ANESTHESIA IN ABDOMINAL SURGERY. PMID- 17857498 TI - FURTHER EXPERIENCES IN THE USE OF SPINAL ANESTHESIA FOR THORACOPLASTY. PMID- 17857500 TI - SYMPATHETIC NERVE BLOCK AS AN ADJUNCT ANESTHESIA IN MINIMAL RESECTION OF THE STOMACH FOR PEPTIC ULCER. PMID- 17857499 TI - INTRAVENOUS AND REGIONAL ANESTHESIA. PMID- 17857501 TI - THE SIGNIFICANCE OF LIPOCAIC IN SURGERY. PMID- 17857502 TI - A DISCUSSION OF MULTIPLE NEUROFIBROMATOSIS (VON RECKLINGHAUSEN'S DISEASE): REPORT OF TWO CASES HAVING UNUSUAL SURGICAL COMPLICATIONS. PMID- 17857503 TI - THE EFFECT ON THE BONE MARROW OF DISRUPTION OF THE NUTRIENT ARTERY AND VEIN. PMID- 17857504 TI - CHONDRITIS OF KNEE. PMID- 17857505 TI - TREATMENT OF AVULSED SKIN FLAPS. PMID- 17857506 TI - CLINICAL AND EXPERIMENTAL EXPERIENCES IN THE SURGICAL TREATMENT OF HYPERTENSION. PMID- 17857507 TI - THE ROLE OF THE PITUITARY GLAND IN WATER BALANCE. PMID- 17857509 TI - THE COMBINED USE OF ZINC PEROXIDE AND SULFANILAMIDE IN THE TREATMENT OF CHRONIC, UNDERMINING, BURROWING ULCERS DUE TO THE MICRO-AEROPHILIC HEMOLYTIC STREPTOCOCCUS. PMID- 17857508 TI - THE CONTROL OF WATER AND ELECTROLYTE BALANCE IN SURGICAL PATIENTS. PMID- 17857510 TI - FAT EMBOLISM. PMID- 17857512 TI - BRIEF COMMUNICATION AND CASE REPORT. PMID- 17857511 TI - REPORT ON THE AMERICAN BOARD OF SURGERY. PMID- 17857513 TI - THE OPERATIVE LENGTHENING OF THE TIBIA AND FIBULA: A PRELIMINARY REPORT ON THE FURTHER DEVELOPMENT OF THE PRINCIPLES AND TECHNIC. PMID- 17857514 TI - A CLINICAL CONSIDERATION OF THE METHODS OF EQUALIZING LEG LENGTH. PMID- 17857515 TI - VITAMIN C STUDIES ON SURGICAL PATIENTS. PMID- 17857517 TI - PHEOCHROMOCYTOMA: CASE REPORT. PMID- 17857516 TI - CHRONIC HYPERTENSION PRODUCED BY CAROTID SINUS AND AORTIC-DEPRESSOR NERVE SECTION. PMID- 17857518 TI - A MODIFIED FORM OF LUMBAR SYMPATHECTOMY FOR DENERVATING THE BLOOD VESSELS OF THE LEG AND FOOT; ANATOMIC CONSIDERATIONS: A PRELIMINARY REPORT. PMID- 17857519 TI - NEW INCISION FOR CLOSED SPACE INFECTION (FELON) INVOLVING DISTAL PHALANX OF FINGER. PMID- 17857520 TI - LUXATION OF EXTENSOR TENDONS IN THE HAND. PMID- 17857521 TI - A METHOD FOR CONTINUOUS SPINAL ANESTHESIA: A PRELIMINARY REPORT. PMID- 17857523 TI - MOTOR FUNCTIONS OF THE STOMACH AFTER RESECTION. PMID- 17857522 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857524 TI - SUBPARIETAL RUPTURE OF THE INTESTINE DUE TO MUSCULAR EFFORT: REPORT OF TWO CASES. PMID- 17857525 TI - THE USE OF SULFANILAMIDE IN THE TREATMENT OF PERITONITIS ASSOCIATED WITH APPENDICITIS. PMID- 17857526 TI - THE MIKULICZ PROCEDURE: WITH SPECIAL REFERENCE TO THE LATE RESULTS IN THE MANAGEMENT OF CARCINOMA OF THE COLON. PMID- 17857527 TI - ADAPTATION OF THE MIKULICZ OPERATION FOR THE RIGHT COLON AND RECTOSIGMOID. PMID- 17857528 TI - DIAGNOSTIC PARACENTESIS IN SUSPECTED INTRA-ABDOMINAL HEMORRHAGE. PMID- 17857529 TI - RECTAL MALFORMATION: CASE REPORT. PMID- 17857530 TI - CONSIDERATIONS IN THE USE OF ULTRAVIOLET RADIATION IN OPERATING ROOMS. PMID- 17857531 TI - THE MILLER-ABBOTT TUBE AS AN ADJUNCT TO SURGERY OF SMALL INTESTINAL OBSTRUCTIONS. PMID- 17857532 TI - ACUTE APPENDICITIS: A TWENTY-YEAR CLINICAL SURVEY. PMID- 17857533 TI - STUDIES OF LIVER FUNCTION BY MEANS OF QUICK'S HIPPURIC ACID TEST. PMID- 17857534 TI - STUDIES ON THE CAUSE OF DEATH IN TETANUS. PMID- 17857535 TI - THYROID DISEASE IN A NONENDEMIC AREA: A THIRD SERIES OF OBSERVATIONS. PMID- 17857536 TI - AUTOGENOUS TRANSPLANTATION OF A FIBROSARCOMA OF SKIN DURING THE APPLICATION OF A FULL-THICKNESS SKIN GRAFT. PMID- 17857537 TI - BLOOD-BORNE PYOGENIC INFECTIONS OF BONES AND JOINTS. PMID- 17857538 TI - THE TREATMENT OF FRACTURES OF THE NECK OF THE FEMUR BY INTERNAL FIXATION. PMID- 17857540 TI - THE ROLE OF SURGERY IN THE MANAGEMENT OF DUODENAL ULCER. PMID- 17857539 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857541 TI - CHRONIC DUODENAL ULCER: PROCEDURES AS DETERMINED BY THE OPERATIVE PATHOLOGY. PMID- 17857542 TI - PROBLEMS IN THE SURGICAL TREATMENT OF CHRONIC DUODENAL ULCERS. PMID- 17857543 TI - PERFORATIONS OF THE GASTRO-INTESTINAL TRACT. PMID- 17857544 TI - POSTAPPENDICEAL ABSCESS IN THE RECTOVESICAL POUCH: TRANSRECTAL DRAINAGE. PMID- 17857545 TI - THE PRESENT STATUS OF CARCINOMA OF THE GALLBLADDER: A STUDY OF THIRTY-FOUR CLINICAL CASES. PMID- 17857546 TI - CARCINOMA OF THE GALLBLADDER: A STUDY OF SEVENTY-FIVE CASES. PMID- 17857547 TI - TORSION OF A WANDERING SPLEEN: COMPLICATED BY DIAPHRAGMATIC HERNIA. PMID- 17857548 TI - THE PREVENTION OF PERITONEAL ADHESIONS WITH HEPARIN: AN EXPERIMENTAL STUDY. PMID- 17857549 TI - MALARIA SIMULATING ACUTE SURGICAL DISEASES OF THE ABDOMEN. PMID- 17857550 TI - CALCIFIED CONSTRICTIVE PERICARDITIS. PMID- 17857551 TI - DANGER IN THE USE OF LOCAL INFILTRATION ANESTHESIA IN OPERATIONS UPON MALIGNANT TUMORS. PMID- 17857552 TI - FOLLICULAR LYMPHOBLASTOMA. PMID- 17857553 TI - THE TREATMENT OF COMPOUND FRACTURES OF THE LONG BONES. PMID- 17857554 TI - ON THE CONTROL OF AIR-BORNE BACTERIA IN OPERATING ROOMS AND HOSPITAL WARDS: A PRELIMINARY REPORT. PMID- 17857555 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857556 TI - PATHOLOGIC CLASSIFICATION, WITH SURGICAL CONSIDERATION, OF INTRASPINAL TUMORS. PMID- 17857558 TI - THROMBOSIS OF THIRD PORTION OF SUBCLAVIAN ARTERY ASSOCIATED WITH SCALENUS ANTICUS SYNDROME. PMID- 17857557 TI - CERVICAL RIBS AND THE SCALENUS MUSCLE SYNDROME. PMID- 17857559 TI - CERVICAL RIB CAUSING PARTIAL OCCLUSION AND ANEURYSM OF THE SUBCLAVIAN ARTERY. PMID- 17857560 TI - PULMONARY EMBOLISM. PMID- 17857562 TI - PERSISTENT SPINAL FLUID FISTULA DUE TO FOREIGN BODY: ASSOCIATED WITH STAB WOUND OF THE HEART WITH RECOVERY. PMID- 17857561 TI - THE INFLUENCE OF CONGESTION UPON TUBERCULOSIS IN THE LUNG OF THE DOG. PMID- 17857563 TI - DUODENOJEJUNOSTOMY FOR CONGENITAL, INTRINSIC, TOTAL ATRESIA AT THE DUODENOJEJUNAL JUNCTION: SUCCESSFUL RESULT IN A THREE-DAY-OLD, ONE-MONTH-PREMATURE INFANT WEIGHING FOUR POUNDS TWO OUNCES. PMID- 17857564 TI - SURGICAL CONSIDERATION OF HYDATID DISEASE: REPORT OF SOME UNUSUAL CASES. PMID- 17857565 TI - LYMPHANGIOMATA OF THE GREAT OMENTUM. PMID- 17857566 TI - LIVING FASCIAL SUTURE IN THE REPAIR OF LARGE INGUINAL HERNIAE. PMID- 17857567 TI - USE OF WHOLE BLOOD AS A MEANS OF PREVENTING PERITONITIS AND ADHESIONS: A PRELIMINARY REPORT. PMID- 17857569 TI - FUNDAMENTAL FACTORS GOVERNING LYMPHATIC SPREAD OF CARCINOMA. PMID- 17857568 TI - THE INTRAVENOUS USE OF SERUM AND PLASMA, FRESH AND PRESERVED. PMID- 17857570 TI - METABOLIC AND BLOOD CHEMICAL CHANGES IN A SEVERE BURN: CASE REPORT. PMID- 17857571 TI - SODIUM MORRHUATE REACTIONS: REPORT OF TWO SEVERE REACTIONS DURING THE INJECTION TREATMENT OF VARICOSE VEINS. PMID- 17857572 TI - MASSIVE DOSES OF LUGOL'S SOLUTION IN ACUTE, SECONDARY PAROTITIS. PMID- 17857573 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857574 TI - MEMOIR: HARVEY (WILLIAMS) CUSHING 1869-1939. PMID- 17857575 TI - ADDRESS OF THE PRESIDENT: THE SURGEON IN THE ROMANTIC STORY OF TEXAS. PMID- 17857576 TI - THE PRESENT STATUS OF THE "RADICAL OPERATION" FOR CARCINOMA OF THE BREAST. PMID- 17857577 TI - THE ROLE OF IRRADIATION IN THE TREATMENT OF CARCINOMA OF THE BREAST. PMID- 17857578 TI - THE SCALENUS ANTICUS SYNDROME WITH AND WITHOUT CERVICAL RIB. PMID- 17857580 TI - PARTIAL GASTRECTOMY: A CONSIDERATION OF CERTAIN TECHNICAL PROBLEMS. PMID- 17857579 TI - THE CERVICOBRACHIAL SYNDROME: A DISCUSSION OF THE ETIOLOGY WITH REPORT OF TWENTY CASES. PMID- 17857581 TI - CHRONIC OBSTRUCTION OF THE PROXIMAL DUODENUM BY CONGENITAL BANDS. PMID- 17857582 TI - NONMALIGNANT OBSTRUCTION OF THE INTESTINE. PMID- 17857583 TI - PENETRATING WOUNDS OF THE ABDOMEN: AN ANALYSIS OF FORTY-SIX PERSONAL CASES. PMID- 17857584 TI - FACTORS OF MORTALITY IN 4,000 OPERATIONS UPON THE EXTERNAL BILIARY SYSTEM. PMID- 17857585 TI - THE IMMEDIATE AND END-RESULTS OF CHOLECYSTECTOMY. PMID- 17857586 TI - THE SURGICAL MANAGEMENT OF STONE IN THE COMMON BILE DUCT: FOLLOW-UP STUDIES WITH SPECIAL REFERENCE TO GRADED DILATATION OF THE SPHINCTER OF ODDI. PMID- 17857588 TI - THE DIAGNOSIS AND TREATMENT OF ACUTE PANCREATITIS. PMID- 17857587 TI - SOLITARY CYSTS OF THE SPLEEN. PMID- 17857589 TI - GRANULOSA CELL TUMOR OF THE OVARY: REPORT OF A CASE. PMID- 17857590 TI - THE MAINTENANCE OF PREGNANCY IN THE HUMAN AFTER REMOVAL OF BOTH OVARIES: CASE REPORT. PMID- 17857591 TI - MODIFIED KONDOLEON OPERATION FOR SCLEROSED LEG WITH ULCERATION. PMID- 17857592 TI - SEMILUNAR CARTILAGES. PMID- 17857593 TI - THE USE OF PRESERVED CARTILAGE IN EAR RECONSTRUCTION. PMID- 17857594 TI - WILLIAM THOMAS BLACK 1875-1938. PMID- 17857595 TI - FRANCIS HENRY HAGAMAN 1896-1939. PMID- 17857596 TI - REGINALD H. JACKSON 1876-1939. PMID- 17857597 TI - WILLIAM BATTLE MALONE 1874-1939. PMID- 17857598 TI - FURTHER EXPERIENCES IN CONSTRUCTION OF THE VAGINA: REPORT OF TWELVE CASES. PMID- 17857600 TI - CASE OF LARGE FALSE ANEURYSM OF THE RIGHT SUBCLAVIAN ARTERY SUCCESSFULLY TREATED BY A MODIFICATION OF THE MATAS OPERATION. PMID- 17857599 TI - CONGENITAL ARTERIOVENOUS ANGIOMA OF THE ARM: METASTASES ELEVEN YEARS AFTER AMPUTATION. PMID- 17857601 TI - HYSTERICAL EDEMA OF THE HAND AND FOREARM. PMID- 17857602 TI - CAISSON DISEASE WITH SPECIAL REFERENCE TO THE BONES AND JOINTS: REPORT OF TWO CASES. PMID- 17857603 TI - A MODIFIED SPUR-CRUSHING CLAMP AND ITS USE. PMID- 17857604 TI - THE SURGICAL TREATMENT OF BRAIN ABSCESS BY EXPOSURE AND ENUCLEATION. PMID- 17857605 TI - THE TREATMENT OF ADDISON'S DISEASE BY THE IMPLANTATION OF SYNTHETIC HORMONE. PMID- 17857606 TI - CYSTS, SINUSES AND FISTULAE OF THE THYROGLOSSAL DUCT: RESULTS IN TWO HUNDRED AND NINETY-THREE SURGICAL CASES. PMID- 17857607 TI - RESULTS OF FACIO-HYPOGLOSSAL ANASTOMOSIS IN THE TREATMENT OF FACIAL PARALYSIS. PMID- 17857608 TI - THE FREQUENCY AND DIAGNOSIS OF HIATAL HERNIA. PMID- 17857609 TI - UMBILICAL AND MIDLINE VENTRAL HERNIAE. PMID- 17857611 TI - THE SUPERIOR PULMONARY SULCUS "TUMOR OF PANCOAST" IN RELATION TO HARE'S SYNDROME. PMID- 17857610 TI - HEMOLYTIC JAUNDICE. PMID- 17857613 TI - LEG AMPUTATIONS IN DIABETIC GANGRENE. PMID- 17857612 TI - URETERAL TRANSPLANTATION. PMID- 17857614 TI - THE INFLUENCE OF SUTURES UPON OPERATIVE WOUNDS. PMID- 17857615 TI - FRACTURE OF THE CAPITELLUM: REPORT OF A CASE SUCCESSFULLY TREATED BY CLOSED REDUCTION. PMID- 17857616 TI - A SUGGESTED IMPROVEMENT TO THE ALLIS' METHOD OF REDUCTION OF POSTERIOR DISLOCATION OF THE HIP. PMID- 17857617 TI - THE EFFECTS OF TEMPERATURE ON THE SURVIVAL OF ANEMIC TISSUE: AN EXPERIMENTAL STUDY. PMID- 17857618 TI - THE FUNCTION OF THE VERTEBRAL VEINS AND THEIR ROLE IN THE SPREAD OF METASTASES. PMID- 17857619 TI - PLASMA TRANSFUSION IN THE TREATMENT OF THE FLUID SHIFT IN SEVERE BURNS. PMID- 17857621 TI - LEIOMYOSARCOMA OF THE STOMACH: REPORT OF THREE CASES. PMID- 17857620 TI - LIVER DAMAGE AND DEXTROSE TOLERANCE IN SEVERE BURNS. PMID- 17857622 TI - TOTAL GASTRECTOMY FOR CARCINOMA OF THE STOMACH. PMID- 17857623 TI - PERFORATIONS OF THE GASTRO-INTESTINAL TRACT-PART TWO. PMID- 17857624 TI - SURGICAL ANASTOMOSES BETWEEN THE BILIARY AND INTESTINAL TRACTS OF CHILDREN: FOLLOW-UP STUDIES. PMID- 17857625 TI - EXPLORATION OF THE COMMON BILE DUCT. PMID- 17857627 TI - LEUKOPLAKIA VULVITIS. PMID- 17857626 TI - CYSTS OF THE MESENTERY. PMID- 17857628 TI - TUMORS OF ISLET CELLS WITH HYPERINSULINISM; BENIGN, MALIGNANT, AND QUESTIONABLE. PMID- 17857629 TI - ACUTE PANCREATITIS AND DIABETES. PMID- 17857630 TI - INDICATIONS FOR LOBECTOMY AND PNEUMONECTOMY IN PULMONARY TUBERCULOSIS. PMID- 17857632 TI - CONSERVATIVE ELECTROSURGICAL EXCISION OF SUBESOPHAGEAL, CHRONIC PENETRATING OR ACUTELY PERFORATED GASTRIC ULCER: REPORT OF AN UNUSUAL CASE THUS TREATED-WITH GOOD END-RESULTS. PMID- 17857631 TI - INJECTIONS OF AIR AND OF CARBON DIOXIDE INTO A PULMONARY VEIN. PMID- 17857633 TI - TUBERCULOSIS OF THE STOMACH: A CLINICAL AND PATHOLOGIC STUDY. PMID- 17857634 TI - LADD'S OPERATION FOR THE CURE OF INCOMPLETE ROTATION AND VOLVULUS OF THE SMALL INTESTINE PRODUCING DUODENAL OBSTRUCTION IN INFANCY. PMID- 17857635 TI - PLASMA TRANSFUSION IN EXPERIMENTAL INTESTINAL OBSTRUCTION. PMID- 17857637 TI - THE DELAYED CLOSURE OF CONTAMINATED WOUNDS: A PRELIMINARY REPORT. PMID- 17857636 TI - METASTATIC PULSATING TUMOR OF BONE SECONDARY TO RENAL CARCINOMA: CASE REPORT. PMID- 17857638 TI - OPERATIVE AND POSTOPERATIVE INFECTIONS WITH SPECIAL REFERENCE TO AIR-BORNE BACTERIAL CONTAMINATION. PMID- 17857639 TI - WOUND INFECTION: A COMPARISON OF SILK AND CATGUT SUTURES. PMID- 17857641 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857640 TI - GRADUATE TEACHING OF SURGICAL PATHOLOGY. PMID- 17857642 TI - CONGENITAL ANOMALIES OF THE DUODENUM. PMID- 17857643 TI - FURTHER OBSERVATIONS ON THE DIAGNOSIS AND TREATMENT OF GASTRIC LESIONS. PMID- 17857644 TI - RETROGRADE ENTERIC INTUSSUSCEPTION. PMID- 17857645 TI - DIVERTICULITIS OF THE COLON WITH SPECIAL REFERENCE TO THE SURGICAL COMPLICATIONS. PMID- 17857646 TI - THE PRODUCTION OF HYPER-AND HYPOMOTILITY OF THE MUSCULATURE OF THE SMALL BOWEL IN THE HUMAN: EXPERIMENTAL STUDIES ON THE: (A) NORMAL PERISTALTIC ACTIVITY (B) EFFECT OF MORPHINE (C) EFFECT OF ATROPINE. PMID- 17857648 TI - CONGENITAL HEMOLYTIC JAUNDICE: REPORT OF A CASE WITH NORMAL FRAGILITY AND NORMAL RETICULOCYTE COUNT, CURED BY SPLENECTOMY. PMID- 17857647 TI - ADENOMA OF THE ISLETS OF LANGERHANS, WITH HYPERINSULINISM, ASSOCIATED WITH ADENOMA OF THE THYROID. PMID- 17857649 TI - ACUTE CHOLECYSTITIS PRECEDING NEOPLASTIC COMMON BILE DUCT OBSTRUCTION. PMID- 17857650 TI - STUDIES ON THE ABSORPTION OF SULFANILAMIDE FROM THE LARGE INTESTINE: RESULTS FOLLOWING THE ADMINISTRATION OF SUPPOSITORIES. PMID- 17857651 TI - STRUMA LYMPHOMATOSA (HASHIMOTO): REPORT OF TWO CASES. PMID- 17857652 TI - BILATERAL AND BILOCULAR EMPYEMA. PMID- 17857654 TI - INTERNAL DERANGEMENTS OF THE KNEE JOINT: AN ANALYSIS OF ONE HUNDRED CASES WITH FOLLOW-UP STUDY. PMID- 17857653 TI - THE TREATMENT OF PERIANAL TUBERCULOSIS. PMID- 17857655 TI - SOME PHYSICAL FACTORS REGARDING CATGUT LIGATURES AND CATGUT KNOTS: A PRELIMINARY REPORT. PMID- 17857656 TI - ANNOUNCEMENT OF A STUDY TO EVALUATE ORIGINAL SEROLOGIC TESTS FOR SYPHILIS. PMID- 17857657 TI - ADDRESS OF THE PRESIDENT: THE CRITICAL LATENT OR LAG PERIOD IN THE HEALING OF WOUNDS. PMID- 17857658 TI - THE STRUCTURE OF THE BLOOD IN RELATION TO SURGICAL PROBLEMS. PMID- 17857659 TI - THE PRESERVATION OF BLOOD. PMID- 17857660 TI - STUDIES IN BLOOD PRESERVATION: THE STABILITY OF PLASMA PROTEINS. PMID- 17857661 TI - SODIUM CHLORIDE METABOLISM OF SURGICAL PATIENTS. PMID- 17857662 TI - FLUID, SALT, AND NUTRITIONAL BALANCE IN PATIENTS WITH INTESTINAL SUCTION DRAINAGE. PMID- 17857663 TI - A CLINICAL STUDY OF THE PLASMA VOLUME IN ACUTE INTESTINAL OBSTRUCTION. PMID- 17857664 TI - PLASMA LOSS IN SEVERE DEHYDRATION, SHOCK AND OTHER CONDITIONS AS AFFECTED BY THERAPY. PMID- 17857665 TI - PHYSIOLOGIC FACTORS REGULATING THE LEVEL OF THE PLASMA PROTHROMBIN. PMID- 17857666 TI - HYPOPROTEINEMIA AND ITS RELATION TO SURGICAL PROBLEMS. PMID- 17857667 TI - FLUID AND NUTRITIONAL MAINTENANCE BY THE USE OF AN INTESTINAL TUBE. PMID- 17857668 TI - PARENTERAL REPLACEMENT OF PROTEIN WITH THE AMINO-ACIDS OF HYDROLYZED CASEIN. PMID- 17857669 TI - THE RELATION OF PROPER PREPARATION OF SOLUTIONS FOR INTRAVENOUS THERAPY TO FEBRILE REACTIONS. PMID- 17857670 TI - GASTRIC ACIDITY BEFORE AND AFTER OPERATIVE PROCEDURE WITH SPECIAL REFERENCE TO THE ROLE OF THE PYLORUS AND ANTRUM: A PRELIMINARY REPORT OF A CLINICAL AND EXPERIMENTAL STUDY. PMID- 17857671 TI - DIAGNOSIS AND SURGICAL MANAGEMENT OF LEIOMYOMATA AND LEIOMYOSARCOMATA OF THE STOMACH. PMID- 17857672 TI - CONGENITAL PYLORIC STENOSIS. PMID- 17857673 TI - ABDOMINAL NEOPLASMS OF NEUROGENIC ORIGIN. PMID- 17857674 TI - ILEOSTOMY. PMID- 17857675 TI - THE SURGICAL MANAGEMENT OF CARCINOMA OF THE LEFT HALF OF THE COLON. PMID- 17857676 TI - IRRADIATION BURN OF THE INTESTINE. PMID- 17857677 TI - EXPERIENCES IN CLEFT PALATE SURGERY. PMID- 17857678 TI - THE USE OF INTRAMUSCULAR INJECTIONS OF 2-METHYL-1, 4-NAPHTHOQUINONE IN THE TREATMENT OF PROTHROMBIN DEFICIENCIES: WITH A NOTE ON THE ROLE OF THE LIVER IN THE RESPONSE TO THIS AND OTHER SUBSTANCES WITH VITAMIN K ACTIVITY. PMID- 17857679 TI - FURTHER ANESTHESIA STUDIES WITH PHOTO-ELECTRIC OXYHEMOGLOBINOGRAPH. PMID- 17857680 TI - GEORGE EMERSON BREWER 1861-1939. PMID- 17857681 TI - ALEXIUS McGLANNAN, A.M., M.D., LL.D. 1872-1940. PMID- 17857682 TI - PERSONAL EXPERIENCES IN VASCULAR SURGERY: A STATISTICAL SYNOPSIS. PMID- 17857683 TI - CLINICAL AND EXPERIMENTAL OBSERVATIONS ON ARTERIOVENOUS FISTULAE. PMID- 17857684 TI - THE SURGICAL TREATMENT OF ANEURYSM OF THE ABDOMINAL AORTA: REVIEW OF THE LITERATURE AND REPORT OF TWO CASES, ONE APPARENTLY SUCCESSFUL. PMID- 17857686 TI - ANEURYSM OF THE ABDOMINAL AORTA AT ITS BIFURCATION INTO THE COMMON ILIAC ARTERIES: A PICTORIAL SUPPLEMENT ILLUSTRATING THE HISTORY OF CORINNE D., PREVIOUSLY REPORTED AS THE FIRST RECORDED INSTANCE OF CURE OF AN ANEURYSM OF THE ABDOMINAL AORTA BY LIGATION. PMID- 17857685 TI - ANEURYSM OF THE ABDOMINAL AORTA: TREATMENT BY LIGATION. PMID- 17857687 TI - EXPERIMENTAL STUDIES ON THE GRADUAL OCCLUSION OF LARGE ARTERIES. PMID- 17857688 TI - THE PREVENTION OF ISCHEMIC GANGRENE FOLLOWING SURGICAL OPERATIONS UPON THE MAJOR PERIPHERAL ARTERIES BY CHEMICAL SECTION OF THE CERVICODORSAL AND LUMBAR SYMPATHETICS. PMID- 17857689 TI - CIRCULATORY DISTURBANCES PRODUCED BY EXTENSIVE ANGIOMATA OF THE LOWER EXTREMITIES ASSOCIATED WITH VARICOSE VEINS. PMID- 17857690 TI - HEPARIN IN THE PREVENTION OF PERITONEAL ADHESIONS: REPORT OF PROGRESS. PMID- 17857691 TI - A DURALUMINUM ENTEROTOME FOR DEVINE COLOSTOMY. PMID- 17857692 TI - STUDIES RELATING TO THE PATHOGENESIS OF CHOLECYSTITIS, CHOLELITHIASIS AND ACUTE PANCREATITIS. PMID- 17857693 TI - THE QUESTION OF DRAINAGE FOLLOWING CHOLECYSTECTOMY. PMID- 17857694 TI - NEUROGENIC DISTURBANCES OF THE COLON AND THEIR INVESTIGATION BY THE COLONMETROGRAM: A PRELIMINARY REPORT. PMID- 17857695 TI - THE EARLY SYMPTOMS AND TREATMENT OF NASOPHARYNGEAL TUMORS. PMID- 17857696 TI - TRANSTHORACIC BRONCHOTOMY FOR REMOVAL OF BENIGN TUMORS OF THE BRONCHI. PMID- 17857697 TI - THE REPAIR OF INGUINAL HERNIA WITH TRANSPLANTATION OF THE CORD TO THE FEMORAL CANAL: A PRELIMINARY REPORT. PMID- 17857698 TI - THE PROBLEM OF PRODUCING COMPLETE AND LASTING SYMPATHETIC DENERVATION OF THE UPPER EXTREMITY BY PREGANGLIONIC SECTION. PMID- 17857699 TI - A ROLE FOR SURGEONS IN THE PROBLEM OF ESSENTIAL HYPERTENSION. PMID- 17857700 TI - FACTORS INFLUENCING THE PROGNOSIS IN OSTEOGENIC SARCOMA. PMID- 17857701 TI - MEMOIR: WILLIAM DAVID HAGGARD 1872-1940. PMID- 17857702 TI - CARCINOMA OF THE THYROID. PMID- 17857703 TI - THE TREATMENT OF STAPHYLOCOCCAL CAVERNOUS SINUS THROMBOPHLEBITIS WITH HEPARIN AND CHEMOTHERAPY. PMID- 17857704 TI - INTRANASAL GRANULOMA OF THE SPOROTHRIX TYPE PRODUCING MARKED NASAL DEFORMITY. PMID- 17857706 TI - INDELIBLE PENCIL INJURIES TO THE HANDS. PMID- 17857705 TI - VARICOCELE AND ITS TREATMENT. PMID- 17857707 TI - AMEBIASIS CUTIS. PMID- 17857708 TI - ACUTE DIVERTICULITIS AND SIGMOIDITIS. PMID- 17857709 TI - BRIEF COMMUNICATION AND CASE REPORT. PMID- 17857711 TI - THE SURGICAL TREATMENT OF INTRACTABLE ULCERATIVE COLITIS. PMID- 17857710 TI - DOCTOR GATEWOOD. PMID- 17857712 TI - LYMPHOGRANULOMA VENEREUM. PMID- 17857714 TI - SURGICAL EMERGENCIES DURING CHILDHOOD CAUSED BY MECKEL'S DIVERTICULUM. PMID- 17857713 TI - A GASTRIC SECRETORY DEPRESSANT IN EXTRACTS OF ACHLORHYDRIC CARCINOMATOUS STOMACHS. PMID- 17857715 TI - ACUTE THROMBOCYTOPENIC PURPURA HEMORRHAGICA ASSOCIATED WITH TUBERCULOSIS (MILIARY) OF THE SPLEEN: SPLENECTOMY-RECOVERY. PMID- 17857716 TI - THE USE OF ERGOTOXINE AND ERGOTAMINE IN THE SURGICAL MANAGEMENT OF THYROTOXICOSIS. PMID- 17857717 TI - COEXISTING CARCINOMATA OF THYROID AND ABERRANT THYROID WITH REGIONAL METASTASES. PMID- 17857718 TI - PAPILLARY ADENOMA OF ABERRANT THYROID. PMID- 17857719 TI - SUBSTERNAL THYROID. PMID- 17857720 TI - AN OSTEOPLASTIC NEUROLYSIS OPERATION FOR THE CURE OF MERALGIA PARESTHETICA. PMID- 17857721 TI - EXTRASKELETAL OSSIFYING TUMORS. PMID- 17857722 TI - FRONTAL LOBECTOMY IN THE TREATMENT OF BRAIN TUMORS. PMID- 17857723 TI - SUBDURAL HEMATOMA: A STUDY OF ONE HUNDRED FORTY-THREE CASES ENCOUNTERED DURING A FIVE-YEAR PERIOD. PMID- 17857724 TI - EXTRADURAL HEMORRHAGE: A STUDY OF FORTY-FOUR CASES. PMID- 17857725 TI - EXTRADURAL VENOUS HEMORRHAGE. PMID- 17857727 TI - OBLITERATION OF THE PLEURAL SPACE FOLLOWING PNEUMONECTOMY. PMID- 17857726 TI - THE SURGICAL TREATMENT, BY DRAINAGE, OF SUBACUTE AND CHRONIC PUTRID ABSCESS OF THE LUNG. PMID- 17857728 TI - RUSSELL TRACTION IN THE TREATMENT OF FRACTURES OF THE FEMUR: OBSERVATIONS ON ONE HUNDRED FIFTY-SIX CASES. PMID- 17857729 TI - TOTAL THYROIDECTOMY FOR HEART DISEASE: A FIVE-YEAR FOLLOW-UP STUDY. PMID- 17857730 TI - CHRONIC GASTRIC ULCER, IN CHILDHOOD, TREATED SURGICALLY. PMID- 17857731 TI - HYDROCELE OF THE FEMORAL HERNIAL SAC. PMID- 17857732 TI - EPIDERMOID CARCINOMA OF THE EXTREMITIES WITH REFERENCE TO LYMPH NODE INVOLVEMENT. PMID- 17857733 TI - HYPOPROTHROMBINEMIA: EFFECT OF PERORAL AND PARENTERAL ADMINISTRATION OF A SYNTHETIC VITAMIN K SUBSTITUTE (2-METHYL-1, 4-NAPHTHOQUINONE). PMID- 17857734 TI - THE LOCAL USE OF SULFANILAMIDE, SULFAPYRIDINE AND SULFAMETHYLTHIAZOL. PMID- 17857735 TI - DEGENERATION AND RECOVERY OF AUTONOMIC NEURONS FOLLOWING ALCOHOLIC BLOCK. PMID- 17857736 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857737 TI - HOMER GAGE. PMID- 17857738 TI - CANCER OF THE BREAST. PMID- 17857739 TI - NIPPLE DISCHARGE: A CLINICOPATHOLOGIC STUDY. PMID- 17857740 TI - SURGICAL TREATMENT OF TUMORS OF THE MEDIASTINUM. PMID- 17857741 TI - HETEROTOPIC PANCREATIC TISSUE PRODUCING PYLORIC OBSTRUCTION: A REVIEW AND CASE REPORT. PMID- 17857742 TI - ILEOJEJUNITIS. PMID- 17857743 TI - NEPHRO-OMENTOPEXY AND NEPHROMYOPEXY IN THE TREATMENT OF ARTERIAL HYPERTENSION. PMID- 17857744 TI - MALIGNANT MELANOMA: A CLINICAL STUDY OF ONE HUNDRED SEVENTEEN CASES. PMID- 17857745 TI - SMOKING AND THROMBO-ANGIITIS OBLITERANS. PMID- 17857746 TI - THE RATE OF HEALING OF TENDONS: AN EXPERIMENTAL STUDY OF TENSILE STRENGTH. PMID- 17857747 TI - PARTIAL MYOTOMY IN THE TREATMENT OF DIVIDED FLEXOR TENDONS OF THE HAND: A REPORT OF TWO CASES. PMID- 17857749 TI - BRIEF COMMUNICATIONS AND CASE REPORT. PMID- 17857748 TI - DISLOCATION OF THE FIRST CERVICAL VERTEBRA. PMID- 17857750 TI - ENDEMIC GOITER IN JAPAN. PMID- 17857751 TI - SURGERY OF THE THYROID IN A LARGE MUNICIPAL HOSPITAL. PMID- 17857752 TI - BRANCHIAL CYSTS AND SINUSES. PMID- 17857753 TI - INTRA-ABDOMINAL APOPLEXY. PMID- 17857754 TI - INTRACTABLE GASTRIC ULCER WITH FINAL MALIGNANT CHANGE ASSOCIATED WITH A BENIGN TUMOR OF THE BRAIN. PMID- 17857755 TI - GIANT DIVERTICULUM OR DUPLICATION OF THE INTESTINE WITH RECURRENT PERFORATIONS. PMID- 17857756 TI - TOPOGRAPHY AND DEVELOPMENT OF THE CECUM-APPENDIX. PMID- 17857757 TI - BENIGN TUMORS OF THE OVARY ASSOCIATED WITH ASCITES AND PLEURAL EFFUSION: REPORT OF A CASE OF MULTILOCULAR CYSTADENOMA. PMID- 17857758 TI - STUDIES ON THE CEREBROSPINAL FLUID PRESSURE IN UNANESTHETIZED DOGS. PMID- 17857759 TI - THE INDUCTION OF LIVER NECROSIS IN RABBITS BY THE COMBINATION OF EXPERIMENTAL HYPERTHYROIDISM AND SHOPE PAPILLOMA. PMID- 17857760 TI - PERINEAL PROSTATOTOMY AND PROSTATECTOMY FOR THE REMOVAL OF PROSTATIC CALCULI. PMID- 17857761 TI - HYDROCELE OF THE CANAL OF NUCK: REPORT OF SEVENTEEN CASES. PMID- 17857763 TI - ADDRESS OF THE PRESIDENT: THE STORY OF PLASTIC SURGERY. PMID- 17857762 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857764 TI - BLOOD AND BLOOD SUBSTITUTES IN THE TREATMENT AND PREVENTION OF SHOCK: WITH PARTICULAR REFERENCE TO THEIR USES IN WARFARE. PMID- 17857765 TI - PERIPHERAL VASCULAR INJURIES. PMID- 17857766 TI - UROGENITAL INJURIES. PMID- 17857767 TI - NJURIES OF THE CHEST. PMID- 17857768 TI - THE ROLE OF THE PLASTIC SURGEON IN THE CARE OF WAR INJURIES. PMID- 17857769 TI - NEW DEVELOPMENTS IN THE TREATMENT OF COMPOUND FRACTURES. PMID- 17857770 TI - WAR WOUNDS OF THE NERVOUS SYSTEM. PMID- 17857771 TI - ABDOMINAL INJURIES: PREVENTIVE AND PROPHYLACTIC ASPECTS. PMID- 17857772 TI - AIDS IN AVOIDING SERIOUS COMPLICATIONS IN THYROIDECTOMY. PMID- 17857773 TI - PRECAUTIONS IN THE TREATMENT OF THYROTOXICOSIS. PMID- 17857775 TI - ENDOCRINE STUDIES OF PATIENTS AFTER SUBTOTAL HYPOPHYSECTOMY. PMID- 17857774 TI - MEDIASTINAL GANGLIONEUROMA. PMID- 17857776 TI - PERFORATED PEPTIC ULCER. PMID- 17857777 TI - RESECTION OF THE DUODENUM FOR TUMOR OF THE AMPULLA OF VATER. PMID- 17857778 TI - SECONDARY OPERATION ON THE BILIARY SYSTEM. PMID- 17857779 TI - ACUTE CHOLECYSTITIS WITH PERFORATION INTO THE PERITONEAL CAVITY. PMID- 17857780 TI - A METHOD OF HANDLING THE APPENDIX STUMP. PMID- 17857782 TI - THE MANAGEMENT OF BILATERAL RENAL STONES: VIEWPOINT OF THE GENERAL SURGEON. PMID- 17857781 TI - END-RESULTS IN REPAIR OF INGUINAL HERNIA BY A FASCIA-TO-FASCIA RECTUS SHEATH CLOSURE. PMID- 17857783 TI - AIR PYELOGRAPHY. PMID- 17857784 TI - THE SURGICAL TREATMENT OF ARTHRITIS. PMID- 17857785 TI - SPONTANEOUS RUPTURE OF THE COMMON BILE DUCT. PMID- 17857786 TI - EMERGENCY TREATMENT OF WAR INJURIES OF THE FACE AND JAWS. PMID- 17857787 TI - THE MEDICAL DEPARTMENT IN NAVAL WARFARE. PMID- 17857788 TI - ORGANIZATION FOR EVACUATION AND TREATMENT OF WAR CASUALTIES. PMID- 17857789 TI - SKIN GRAFTING AND THE "THREE-QUARTER"-THICKNESS SKIN GRAFT FOR PREVENTION AND CORRECTION OF CICATRICIAL FORMATION. PMID- 17857791 TI - GASTRIC RESECTION FOR ULCER: EXPERIENCE IN FORTY-FOUR CASES. PMID- 17857790 TI - TREATMENT OF COMPOUND INJURIES BY THE CLOSED PLASTER ENCASEMENT METHOD. PMID- 17857792 TI - REGIONAL LYMPHATIC METASTASES OF CARCINOMA OF THE STOMACH. PMID- 17857794 TI - SURGERY IN ULCERATIVE COLITIS. PMID- 17857793 TI - REGIONAL ENTERITIS: REPORT OF CASES. PMID- 17857796 TI - BILE PERITONITIS. PMID- 17857795 TI - DIVERTICULITIS OF THE COLON. PMID- 17857797 TI - THE FORGOTTEN MOYNIHAN TUBE: IN ACUTE MECHANICAL OBSTRUCTION OF THE SMALL INTESTINE. PMID- 17857798 TI - DIFFERENTIAL DIAGNOSIS AND SURGICAL CARE OF JAUNDICED PATIENTS. PMID- 17857799 TI - A CLINICAL STUDY OF CARCINOMA OF THE GALLBLADDER. PMID- 17857800 TI - INTRAPERITONEAL SULFANILAMIDE. PMID- 17857802 TI - RESULTS OF CONSERVATIVE TREATMENT OF ACUTE PANCREATITIS. PMID- 17857801 TI - A MODIFICATION OF "T"-TUBE DRAIN WHICH WILL PERMIT PASSING A CATHETER INTO THE COMMON BILE DUCT. PMID- 17857803 TI - PHEOCHROMOCYTOMA: A REPORT OF THREE CASES. PMID- 17857805 TI - A CRITIQUE OF THE SURGICAL TREATMENT OF HYPERTENSION. PMID- 17857804 TI - THE SURGICAL TREATMENT OF HYPERTENSION: PRELIMINARY REPORT OF COMPARISON OF MORTALITY FOLLOWING OPERATION WITH THAT OF A MEDICALLY TREATED CONTROL SERIES (WAGENER-KEITH) TENTATIVE CORRELATION OF RESULTS WITH RECENT EXPERIMENTAL WORK. PMID- 17857806 TI - THE RELATION OF HYPERTHYROIDISM TO HYPERTENSION. PMID- 17857807 TI - "SHORT-INTERVAL" STAGE THYROIDECTOMIES: A FURTHER REPORT. PMID- 17857808 TI - DIAGNOSIS AND TREATMENT OF GLOSSOPHARYNGEAL NEURALGIA. PMID- 17857809 TI - EXPERIMENTAL AND CLINICAL OBSERVATIONS ON THE SYNDROME OF PINEAL GLAND DESTRUCTION. PMID- 17857810 TI - THE USE OF CELLULOID PLATE TO COVER SKULL DEFECTS: CASE REPORTS. PMID- 17857811 TI - A REVIEW OF FIFTEEN YEARS' EXPERIENCE WITH EMPYEMA IN INFANTS AND CHILDREN. PMID- 17857813 TI - HEPARIN ADMINISTRATION: METHODS AND RESULTS IN THIRTY CASES. PMID- 17857812 TI - PULMONARY EMBOLISM: CLINICAL AND EXPERIMENTAL. PMID- 17857814 TI - MEDIASTINAL CYSTS. PMID- 17857815 TI - A METHOD FOR PLASMA PREPARATION AND PRESERVATION FOR INTRAVENOUS USE. PMID- 17857816 TI - PLASMA THERAPY OF BURNS. PMID- 17857817 TI - A CRITICAL EVALUATION OF THE TREATMENT OF BURNS. PMID- 17857818 TI - DEFORMITIES DUE TO BURNS. PMID- 17857819 TI - THE TREATMENT OF COMPLETE DISLOCATION OF THE OUTER END OF THE CLAVICLE: AN HITHERTO UNDESCRIBED OPERATION. PMID- 17857820 TI - PROGRESS IN THE MANAGEMENT OF SEVERE SUPRACONDYLAR FRACTURES OF THE ELBOW. PMID- 17857821 TI - AMPUTATIONS THROUGH FINGERS. PMID- 17857822 TI - WRINGER INJURIES OF THE UPPER EXTREMITY. PMID- 17857823 TI - TENDON IMPLANTATIONS TO BONE: A STUDY OF THE FACTORS AFFECTING TENDON-BONE UNION AS DETERMINED BY THE TENSILE STRENGTH. PMID- 17857824 TI - TUBERCULOSIS OF THE HIP: A REVIEW OF SEVENTY-SIX CASES WITH PROVEN TUBERCULOUS ARTHRITIS OF SEVENTY-SEVEN HIPS TREATED BY ARTHRODESIS. PMID- 17857825 TI - THE USE OF HORMONE THERAPY IN CRYPTORCHIDISM. PMID- 17857826 TI - A FIRST STAGE OPERATIVE METHOD IN THE TREATMENT OF HYPOSPADIAS. PMID- 17857827 TI - THROMBO-ANGIITIS OBLITERANS: CLINICAL OBSERVATIONS AND ARTERIAL BLOOD OXYGEN STUDIES DURING TREATMENT OF THE DISEASE WITH SODIUM TETRATHIONATE AND SODIUM THIOSULFATE. PMID- 17857828 TI - INDIVIDUALIZATION IN THE SURGICAL TREATMENT OF VARICOSE VEINS. PMID- 17857829 TI - AN ANATOMIC ERROR IN CURRENT METHODS OF INGUINAL HERNIORRHAPHY. PMID- 17857830 TI - THE PROPHYLAXIS OF HUMAN BITE INFECTIONS. PMID- 17857831 TI - BENEFICIAL EFFECT OF OXYGEN THERAPY IN SHOCK. PMID- 17857832 TI - EXPERIMENTAL WORK ON ALIMENTARY AZOTEMIA. PMID- 17857833 TI - THE FUNCTIONS OF THE ANESTHESIOLOGIST. PMID- 17857834 TI - CESSATION OF RESPIRATORY EXCHANGE. PMID- 17857835 TI - THE PROBLEM OF CATGUT SENSITIVITY AND ITS RELATIONSHIP TO WOUND HEALING: A PRELIMINARY REPORT. PMID- 17857836 TI - TWO DISTINCT TYPES OF DEHYDRATION: A PRELIMINARY REPORT. PMID- 17857837 TI - ADDRESS OF THE PRESIDENT: MARS AND AESCULAPIUS. PMID- 17857839 TI - SURGERY OF AIR RAID CASUALTIES. PMID- 17857838 TI - SURGICAL PROBLEMS OF THE WAR. PMID- 17857840 TI - THE TREATMENT OF COMPOUND FRACTURES RESULTING FROM ENEMY ACTION. PMID- 17857841 TI - THE EXPERIENCE OF THE CANADIAN ARMY AND PENSIONS BOARD WITH AMPUTATIONS OF THE LOWER EXTREMITY. PMID- 17857842 TI - MINOR CAUSALGIA FOLLOWING INJURIES AND WOUNDS. PMID- 17857843 TI - PRESENT-DAY TREATMENT OF COMPOUND FRACTURES. PMID- 17857844 TI - THE USE OF ADRENAL CORTICAL EXTRACT IN THE TREATMENT OF TRAUMATIC SHOCK OF BURNS. PMID- 17857845 TI - THE THERAPEUTIC VALUE OF PRESERVED BLOOD PLASMA: A SUMMARY OF ONE HUNDRED AND TEN CASES. PMID- 17857846 TI - B.I.P.P. AND LIQUID PARAFFIN TREATMENT OF WAR AND CIVILIAN WOUNDS. PMID- 17857847 TI - MEDICINE IN THE NATIONAL DEFENSE PROGRAM. PMID- 17857848 TI - SECONDARY REPAIR OF CLEFT LIPS AND THEIR NASAL DEFORMITIES. PMID- 17857849 TI - WHY INGUINAL HERNIA RECURS. PMID- 17857851 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857850 TI - CHEMOTHERAPY AS AN AID IN THE MANAGEMENT OF ACUTE OSTEOMYELITIS. PMID- 17857852 TI - THE USE OF SULFANILYLGUANIDINE IN SURGICAL PATIENTS. PMID- 17857853 TI - PNEUMONECTOMY. PMID- 17857854 TI - THE TREATMENT OF FRESH TRAUMATIC WOUNDS. PMID- 17857855 TI - MORTALITY FACTORS IN THE SURGICAL TREATMENT OF ULCERATIVE COLITIS. PMID- 17857857 TI - RECURRENT CARCINOMA OF THE RECTUM. PMID- 17857856 TI - REGIONAL LYMPHATIC METASTASES OF CARCINOMA OF THE COLON. PMID- 17857858 TI - RESULTS WITH THE FASCIA PLASTIC OPERATION FOR ANAL INCONTINENCE. PMID- 17857860 TI - CARCINOMA OF THE FUNDUS OF THE UTERUS. PMID- 17857859 TI - ARRHENOBLASTOMA OF THE OVARY. PMID- 17857861 TI - THE COOPERATION BETWEEN THE ARMY SERVICES OF EVACUATION AND HOSPITALIZATION. PMID- 17857862 TI - THE DIAGNOSIS AND TREATMENT OF CARDIAC TRAUMA. PMID- 17857863 TI - AN EFFECTIVE METHOD FOR THE DEVELOPMENT OF COLLATERAL CIRCULATION TO THE MYOCARDIUM. PMID- 17857864 TI - THE TREATMENT OF VASCULAR INJURIES. PMID- 17857865 TI - RADICAL OPERATIVE TREATMENT FOR SUPPURATIVE PHLEBITIS AND ITS RESULTS. PMID- 17857866 TI - HEPARIN ADMINISTRATION: METHODS AND RESULTS IN THIRTY CASES. PMID- 17857868 TI - CANCER OF THE LIP: PART I. PMID- 17857867 TI - PECTIN SOLUTION AS A BLOOD SUBSTITUTE. PMID- 17857869 TI - OBSERVATIONS ON THE PREVENTION AND TREATMENT OF POSTOPERATIVE ATELECTASIS AND BRONCHOPNEUMONIA. PMID- 17857870 TI - ROENTGEN RAY TREATMENT OF GAS GANGRENE: CLINICAL AND EXPERIMENTAL OBSERVATIONS. PMID- 17857871 TI - CONSERVATIVE AMPUTATION OF GANGRENOUS PARTS BY CHEMOSURGERY. PMID- 17857872 TI - A PLAN FOR THE STUDY OF WAR WOUNDS. PMID- 17857873 TI - PROCAINE INJECTION AND EARLY MOBILIZATION IN THE TREATMENT OF NON-WEIGHT-BEARING FRACTURES. PMID- 17857875 TI - A SIMPLIFIED ARTHROMETER. PMID- 17857874 TI - THREE YEARS' EXPERIENCE WITH VITALLIUM IN BONE SURGERY. PMID- 17857876 TI - CORRESPONDENCE. PMID- 17857877 TI - EXPERIMENTAL CEREBRAL TRAUMA: III. THE EFFECTS OF ACUTE UREMIA, OF VENOUS OBSTRUCTION, OF HYPERTHERMIA, AND OF INTENSIVE IRRADIATION ON THE WATER CONTENT OF THE DOG'S BRAIN. PMID- 17857878 TI - CEREBELLAR ABSCESSES OF OTITIC ORIGIN IN NINE CHILDREN: EIGHT RECOVERIES AFTER CANNULATION. PMID- 17857879 TI - THE SURGICAL TREATMENT OF INTRACRANIAL ANEURYSMS OF THE INTERNAL CAROTID ARTERY. PMID- 17857880 TI - CANCER OF THE LIP: PART II. PMID- 17857881 TI - PERFORATION OF THE CERVICAL ESOPHAGUS WITH THE FLEXIBLE GASTROSCOPE: CASE REPORT DIAGNOSIS-TREATMENT. PMID- 17857883 TI - MORBID INFLUENCES IN INTESTINAL OBSTRUCTION AND STRANGULATION. PMID- 17857882 TI - ACTUAL HOLDING POWER OF VARIOUS SCREWS IN BONE. PMID- 17857884 TI - THE MUSCULAR ACTIVITY OF THE SMALL INTESTINE, IN THE DOG, DURING ACUTE OBSTRUCTION. PMID- 17857885 TI - THE SIGNIFICANCE OF NEUROMATOUS LESIONS IN OBLITERATED APPENDICES: A CLINICOPATHOLOGIC STUDY. PMID- 17857886 TI - THE INFLUENCE OF THE EXTERNAL SECRETION OF THE PANCREAS ON LIPID METABOLISM. PMID- 17857887 TI - THE ROLE OF THE SECOND THORACIC SPINAL SEGMENT IN THE PREGANGLIONIC SYMPATHETIC INNERVATION OF THE HUMAN HAND-SURGICAL IMPLICATIONS. PMID- 17857889 TI - STUDIES ON THE USE OF METALS IN SURGERY. PMID- 17857888 TI - JEJUNOSTOMY FOR POSTOPERATIVE FEEDING. PMID- 17857890 TI - RESULTS OF PARTIAL GASTRECTOMY FOR BLEEDING DUODENAL, GASTRIC, AND GASTROJEJUNAL ULCER. PMID- 17857891 TI - GASTRIC ULCER: THE SIGNIFICANCE OF THIS DIAGNOSIS AND ITS RELATIONSHIP TO CANCER. PMID- 17857892 TI - MASSIVE GASTRIC HEMORRHAGE: WITH SPECIAL REFERENCE TO PEPTIC ULCER. PMID- 17857894 TI - SURGICAL PROBLEMS IN THE TREATMENT OF GASTROJEJUNAL ULCERATION. PMID- 17857893 TI - SURGERY IN PEPTIC ULCERATION OF STOMACH AND DUODENUM IN INFANTS AND CHILDREN. PMID- 17857895 TI - SURGICAL MANAGEMENT OF CARCINOMA OF THE AMPULLA OF VATER AND OF THE PERIAMPULLARY PORTION OF THE DUODENUM. PMID- 17857896 TI - FIFTY-TWO PROVEN CASES OF CARCINOMA OF THE PANCREAS AND THE AMPULLA OF VATER: WITH SPECIAL REFERENCE TO FATTY INFILTRATION OF THE LIVER. PMID- 17857897 TI - THE RATIONALE OF RADICAL SURGERY FOR CANCER OF THE PANCREAS AND AMPULLARY REGION. PMID- 17857898 TI - ANASTOMOSIS OF THE BILE DUCTS TO THE GASTRO-INTESTINAL TRACT BY A METHOD OF TRANSFIXION NECROSING SUTURE. PMID- 17857899 TI - ASEPTIC, IMMEDIATE ANASTOMOSIS FOLLOWING RESECTION OF THE COLON FOR CARCINOMA. PMID- 17857900 TI - CHRONIC ULCERATIVE COLITIS: A SUMMARY OF EVIDENCE IMPLICATING BACTERIUM NECROPHORUM AS AN ETIOLOGIC AGENT. PMID- 17857901 TI - INTESTINAL ANTISEPSIS, WITH SPECIAL REFERENCE TO SULFANILYLGUANIDINE. PMID- 17857902 TI - THE SYNDROME OF MESENTERIC OR SUBPERITONEAL HEMORRHAGE (ABDOMINAL APOPLEXY). PMID- 17857904 TI - CEREBROSPINAL RHINORRHEA: SURGICAL REPAIR OF CRANIOSINUS FISTULA. PMID- 17857903 TI - EXPERIMENTAL PRODUCTION OF CHRONIC CHOLECYSTITIS BY OBSTRUCTIVE LESION OF THE CYSTIC DUCT. PMID- 17857905 TI - SURGERY OF HYPERPARATHYROIDISM: THE OCCURRENCE OF PARATHYROIDS IN THE ANTERIOR MEDIASTINUM AND THE DIVISION OF THE OPERATION INTO TWO STAGES. PMID- 17857906 TI - OBSERVATIONS ON INTRATHORACIC NEOPLASMS. PMID- 17857907 TI - TOTAL THORACIC AND PARTIAL TO TOTAL LUMBAR SYMPATHECTOMY AND CELIAC GANGLIONECTOMY IN THE TREATMENT OF HYPERTENSION. PMID- 17857909 TI - THE EFFECT OF THE LOCAL AND ORAL ADMINISTRATION OF COD LIVER OIL ON THE RATE OF WOUND HEALING IN VITAMIN A-DEFICIENT AND NORMAL RATS. PMID- 17857908 TI - ASCORBIC ACID AND HUMAN WOUND HEALING. PMID- 17857910 TI - TABLE TOP FOR ROENTGENOGRAPHY, ESPECIALLY OF THE BILIARY TRACT, DURING OPERATION. PMID- 17857911 TI - THE PROPHYLAXIS OF PULMONARY EMBOLISM BY DIVISION OF THE FEMORAL VEIN. PMID- 17857912 TI - THE MANAGEMENT OF LYMPH NODES IN THE NECK-METASTATIC FROM CARCINOMA OF THE MOUTH. PMID- 17857913 TI - TUMORS OF THE CAROTID BODY: CLINICAL AND PATHOLOGIC CONSIDERATIONS OF TWENTY TUMORS AFFECTING NINETEEN PATIENTS (ONE BILATERAL). PMID- 17857914 TI - THE SUCCESSFUL REMOVAL OF A SADDLE EMBOLUS OF THE AORTA, 11 DAYS AFTER ACUTE CORONARY OCCLUSION. PMID- 17857915 TI - REFLECTIONS ON GASTRODUODENAL SURGERY. PMID- 17857916 TI - LYMPHOGRANULOMA VENEREUM: TREATMENT OF SEVERE CASES OF ANORECTAL TYPE BY A MUCOSAL-STRIPPING OPERATION: A PRELIMINARY REPORT. PMID- 17857917 TI - ENDOMETRIOSIS-ITS SIGNIFICANCE. PMID- 17857918 TI - INTRA-ABDOMINAL HERNIA: REVIEW OF 39 CASES IN WHICH TREATMENT WAS SURGICAL. PMID- 17857920 TI - THE PRESENT STATUS OF INTRAVENOUS FLUID TREATMENT OF TRAUMATIC AND SURGICAL SHOCK. PMID- 17857919 TI - TESTICULAR TRANSPLANTATION: SUCCESSFUL AUTOPLASTIC GRAFT FOLLOWING ACCIDENTAL CASTRATION. PMID- 17857922 TI - THE TREATMENT OF FRACTURES OF THE HUMERUS BY MEANS OF A HANGING PLASTER CASE "HANGING CAST". PMID- 17857921 TI - CLINICAL SIGNIFICANCE OF PROTHROMBIN DEFICIENCY AND ITS TREATMENT. PMID- 17857923 TI - THE EARLY DIAGNOSIS OF POTT'S DISEASE. PMID- 17857924 TI - "UNEXPLAINED" INFECTIONS IN CLEAN OPERATIVE WOUNDS: THE IMPORTANCE OF THE AIR AS A MEDIUM FOR THE TRANSMISSION OF PATHOGENIC BACTERIA; AND BACTERICIDAL RADIATION AS A METHOD OF CONTROL ANALYSIS OF OVER FIVE THOUSAND OPERATIONS, COVERING A PERIOD OF TEN AND ONE-HALF YEARS. PMID- 17857925 TI - PRELIMINARY COLOSTOMY IN THE MANAGEMENT OF GASTROCOLIC AND GASTROJEJUNOCOLIC FISTULAE. PMID- 17857926 TI - THE SURGICAL MANAGEMENT OF FECAL FISTULAE. PMID- 17857927 TI - THE LIVER GLYCOGEN AND LIPID CONCENTRATIONS FOLLOWING INTRAVENOUS ADMINISTRATION AND DIET IN THE DOG AND MAN IN THE PRESENCE OF LIVER DAMAGE. PMID- 17857928 TI - TORSION OF THE GREAT OMENTUM: REPORT OF TWO CASES. PMID- 17857929 TI - RIGHT PARADUODENAL HERNIA. PMID- 17857930 TI - MANAGEMENT OF VARICOSE VEINS OF THE LOWER EXTREMITIES. PMID- 17857931 TI - VISUALIZATION AND OBLITERATION OF ANGIOMATA BY RADIOPAQUE SOLUTIONS. PMID- 17857933 TI - THE INFLUENCE OF TEMPERATURE ON WOUNDS. PMID- 17857932 TI - ACTIVE IMMUNIZATION AGAINST TETANUS. PMID- 17857934 TI - REGENERATION OF EPIPHYSEAL CARTILAGE: AN EXPERIMENTAL STUDY. PMID- 17857935 TI - INFUSIONS OF BLOOD AND OTHER FLUIDS VIA THE BONE MARROW IN TRAUMATIC SHOCK AND OTHER FORMS OF PERIPHERAL CIRCULATORY FAILURE. PMID- 17857936 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857937 TI - BLOOD TRANSFUSION REACTIONS: THEIR CAUSES AND PREVENTION. PMID- 17857938 TI - THE TREATMENT OF CERVICAL METASTATIC CANCER. PMID- 17857939 TI - PSEUDOGASTRITIS OF OPERATIVE ORIGIN. PMID- 17857940 TI - RUPTURE OF THE STOMACH FOLLOWING INGESTION OF SODIUM BICARBONATE. PMID- 17857941 TI - PRIMARY, SOLITARY LYMPHOID TUMORS OF THE GASTRO-INTESTINAL TRACT. PMID- 17857942 TI - KRUKENBERG'S TUMORS: A SURVEY OF FORTY-FOUR CASES. PMID- 17857943 TI - DESMOID TUMORS: A CLINICAL AND PATHOLOGIC STUDY. PMID- 17857944 TI - TECHNIC OF TATTOOING WITH MERCURY SULFIDE FOR PRURITUS ANI. PMID- 17857945 TI - RUPTURE OF THE COLON BY COMPRESSED AIR: REPORT OF THREE CASES. PMID- 17857946 TI - VARICOSE VEINS: AN ANALYSIS OF THE RESULTS OF VARIOUS OPERATIVE PROCEDURES. PMID- 17857947 TI - THE PROBLEM OF CATGUT SENSITIVITY AND ITS RELATION TO WOUND HEALING: A PRELIMINARY REPORT. PMID- 17857948 TI - THE ROLE OF THE LIVER IN PREOPERATIVE CARE. PMID- 17857950 TI - CORRESPONDENCE. PMID- 17857949 TI - BRIEF COMMUNICATION: THE ADVANTAGES OF COMBINING LOCAL INFILTRATION ANESTHESIA WITH CONTROLLED FRACTIONAL SPINAL ANESTHESIA IN SUBSTANDARD SURGICAL RISKS. PMID- 17857951 TI - CONGENITAL MALFORMATIONS OF THE APPENDIX-A FAMILIAL DISEASE. PMID- 17857952 TI - OBSTRUCTIVE JAUNDICE DUE TO CARCINOMA OF THE PANCREAS: THE CHOICE OF OPERATIVE PROCEDURE. PMID- 17857953 TI - ILEUS FOLLOWING FRACTURED RIBS. PMID- 17857954 TI - THE EFFECT OF THE SULFONAMIDES ON THE PREVENTION OF EXPERIMENTAL BRAIN ABSCESS. PMID- 17857955 TI - THE RELATION OF HYPERTHYROIDISM TO HYPERTENSION. PMID- 17857956 TI - METASTATIC TUMORS IN THE BREAST. PMID- 17857957 TI - NEOPLASMS OF THE BONY THORACIC WALL. PMID- 17857958 TI - AUTOPLASTIC TRANSPLANTATION OF SPLENIC TISSUE, IN MAN, FOLLOWING TRAUMATIC RUPTURE OF THE SPLEEN. PMID- 17857959 TI - AN UNUSUAL CASE OF BENIGN MULTIPLE CHORIONIC VILLI IMPLANTS IN PERITONEAL CAVITY ACCOMPANIED BY HEMOPERITONEUM. PMID- 17857960 TI - LATERAL ABERRANT THYROIDS. PMID- 17857961 TI - MASKED HYPERTHYROIDISM. PMID- 17857962 TI - THE END-RESULTS OF THYROIDECTOMY. PMID- 17857963 TI - IODINE METABOLISM IN THYROID DISEASE: CLINICAL AND EXPERIMENTAL OBSERVATIONS. PMID- 17857964 TI - CARDIOSPASM. PMID- 17857965 TI - THE MANAGEMENT OF APPENDICEAL PERITONITIS-WITH SPECIAL REFERENCE TO THE OPERATIVE HANDLING OF THE LOCALIZED ABSCESS. PMID- 17857966 TI - BILE PERITONITIS: REPORT OF EIGHT CASES. PMID- 17857967 TI - BLACK WIDOW SPIDER BITE. PMID- 17857968 TI - SEBACEOUS GLAND CARCINOMA. PMID- 17857970 TI - PRIMARY RETICULUM CELL SARCOMA OF BONE: REPORT OF TWO CASES WITH BONE REGENERATION FOLLOWING ROENTGENOTHERAPY. PMID- 17857969 TI - NEUROPATHIC ARTHROPATHY OF THE ANKLE JOINT RESULTING FROM COMPLETE SEVERANCE OF THE SCIATIC NERVE. PMID- 17857971 TI - UROLOGY AWARD. PMID- 17857972 TI - PERIPHERAL ARTERIOSCLEROSIS. PMID- 17857974 TI - BRIEF COMMUNICATION: DISARTICULATION OF THE HIP FOR ENDOTHELIOMA (EWING'S TUMOR): 31-YEAR FOLLOW-UP. PMID- 17857973 TI - THE TREATMENT OF SEVERE STAPHYLOCOCCAL INFECTION WITH SPECIFIC TYPE-A ANTIBACTERIAL SERUM. PMID- 17857975 TI - EARLY SKIN GRAFTING IN WAR WOUNDS OF THE EXTREMITIES. PMID- 17857976 TI - BRAIN ABSCESS OF UNCOMMON ORIGIN-RELATION TO OSTEOMYELITIS OF THE SKULL: A CLINICOPATHOLOGIC STUDY. PMID- 17857977 TI - GASTRIC POLYPOSIS: REPORT OF A CASE OF "polyadenomes en nappe," DIAGNOSED GASTROSCOPICALLY. PMID- 17857978 TI - ADENOMA OF THE PANCREAS: CASE REPORTS. PMID- 17857979 TI - THE MANAGEMENT OF URETERAL CALCULI. PMID- 17857980 TI - MALIGNANT TUMORS DEVELOPING IN SACROCOCCYGEAL TERATOMATA. PMID- 17857981 TI - STUDIES ON THE BLOOD HISTAMINE IN CASES OF BURNS. PMID- 17857983 TI - MALIGNANT TUMORS OF SYNOVIAL ORIGIN. PMID- 17857982 TI - A STUDY OF THE WEIGHT OF THE CELIAC GANGLION AND ITS RELATIONSHIP TO ESSENTIAL HYPERTENSION: REPORT UPON 201 CELIAC GANGLIA. PMID- 17857984 TI - CHOICE OF BONE GRAFT METHODS IN BONE AND JOINT SURGERY. PMID- 17857986 TI - AN OPERATIVE TREATMENT FOR RECURRENT DISLOCATION OF THE SHOULDER. PMID- 17857985 TI - INTERINNOMINO-ABDOMINAL AMPUTATION: CASE REPORT. PMID- 17857987 TI - SUBTALAR DISLOCATIONS: CASE REPORT OF THE INWARD TYPE. PMID- 17857989 TI - BRIEF COMMUNICATIONS AND CASE REPORTS. PMID- 17857988 TI - THE THIRD PHASE OF SURGERY: TOTAL STERILIZATION AS A BASIS OF INTEGRAL ASEPSIS AND OF PASTEURIAN CICATRIZATION. PMID- 17857990 TI - MEMORIAL COLLECTION FOR DR. JOHN B. DEAVER. PMID- 17857991 TI - ADDRESS OF THE PRESIDENT: "ONCE AGAIN". PMID- 17857992 TI - OXYCEPHALY. PMID- 17857993 TI - TREATMENT OF COMPOUND FRACTURES OF THE SKULL. PMID- 17857994 TI - RECENT ADVANCES IN THE DIAGNOSIS AND TREATMENT OF RUPTURED INTERVERTEBRAL DISKS. PMID- 17857995 TI - GASTRIC ULCER, CARCINOMATOUS ULCER OR ULCERATING CARCINOMA. PMID- 17857996 TI - GASTRIC RESECTION FOR DUODENAL ULCER: FOLLOW-UP STUDIES. PMID- 17857997 TI - SARCOMA OF THE SMALL INTESTINE: REPORT OF FOUR CASES. PMID- 17857998 TI - EXTENSION OF THE BORDER LINE OF OPERABILITY IN CANCER OF THE RECTUM. PMID- 17857999 TI - ANNULAR PANCREAS AS A CLINICAL PROBLEM. PMID- 17858000 TI - EFFECT OF REMOVAL OF MALIGNANT THYMIC TUMOR IN A CASE OF MYASTHENIA GRAVIS. PMID- 17858001 TI - SUCCESSFUL EXPERIMENTAL LIGATION AND DIVISION OF THE THORACIC AORTA. PMID- 17858003 TI - IMPROVED METHODS IN EXTREMITY AMPUTATIONS FOR DIABETIC GANGRENE. PMID- 17858002 TI - GAS GANGRENE: REVIEW OF SEVENTY-ONE CASES. PMID- 17858004 TI - INTERINNOMINO-ABDOMINAL (HINDQUARTER) AMPUTATION. PMID- 17858005 TI - THE SURGICAL CORRECTION OF MANDIBULAR PROGNATHISM. PMID- 17858006 TI - SPRAINED ANKLES. PMID- 17858007 TI - MASSIVE REPAIRS OF BURNS WITH THICK SPLIT-SKIN GRAFTS: EMERGENCY "DRESSINGS" WITH HOMOGRAFTS. PMID- 17858009 TI - THE UNIFORM PRODUCTION OF EXPERIMENTAL SHOCK BY CRUSH INJURY: POSSIBLE RELATIONSHIP TO CLINICAL CRUSH SYNDROME. PMID- 17858008 TI - TRENDS IN SURGERY. PMID- 17858010 TI - FURTHER OBSERVATIONS ON STAB WOUNDS OF THE HEART. PMID- 17858011 TI - DIAPHRAGMATIC HERNIA OF CHILDREN. PMID- 17858012 TI - BRIEF COMMUNICATION: INTRAMAMMARY HEMANGIOMA. PMID- 17858013 TI - INTESTINAL OBSTRUCTION FROM GALLSTONES. PMID- 17858014 TI - THE SURGICAL ASPECT OF CONGENITAL ABSENCE OF THE GALLBLADDER: REPORT OF TWO CASES. PMID- 17858015 TI - ANATOMY OF THE ATTACHMENTS OF THE DIAPHRAGM: THEIR RELATION TO THE PROBLEMS OF THE SURGERY OF DIAPHRAGMATIC HERNIA. PMID- 17858016 TI - AN OPERATION FOR THE CURE OF INGUINAL HERNIA. PMID- 17858017 TI - A METHOD OF DISPOSAL OF THE SAC IN OPERATIONS FOR OBLIQUE INGUINAL HERNIA. PMID- 17858018 TI - THE USE OF THE CUTIS GRAFT IN THE REPAIR OF CERTAIN TYPES OF INCISIONAL HERNIAE AND OTHER CONDITIONS. PMID- 17858019 TI - RETROVAGINAL HERNIA. PMID- 17858021 TI - SPLENECTOMY. PMID- 17858020 TI - ACUTE HEMATOGENOUS OSTEOMYELITIS. PMID- 17858022 TI - THE USE OF ESTROGENIC SUBSTANCES IN THE PRE- AND POSTOPERATIVE TREATMENT OF HYPERTHYROIDISM: FURTHER OBSERVATIONS. PMID- 17858023 TI - INTESTINAL ANTISEPSIS WITH SULFONAMIDES. PMID- 17858025 TI - FINNEY-HOWELL RESEARCH FOUNDATION, INC. PMID- 17858024 TI - URETERAL TRANSPLANTATION AND CYSTECTOMY: COMPARISON OF RESULTS AFTER EIGHT YEARS. PMID- 17858026 TI - THE TREATMENT OF TRICHOMONAS VAGINALIS VAGINITIS WITH THE LACTOBACILLUS. PMID- 17858028 TI - ABDUCEUS NERVE (VI) PARALYSIS FOLLOWING SPINAL ANESTHESIA. PMID- 17858027 TI - ACOUSTIC TUMORS: WITH SPECIAL REFERENCE TO END-RESULTS AND SPARING OF THE FACIAL NERVE. PMID- 17858029 TI - THE DEFORMED CHIN AND LOWER JAW. PMID- 17858031 TI - OPERATIVE REPAIR OF MASSIVE RECTAL PROLAPSE. PMID- 17858030 TI - BRIEF COMMUNICATION: AN IMPROVED BIOPSY PUNCH. PMID- 17858032 TI - TESTS OF HEPATIC AND PANCREATIC FUNCTION IN THE DIFFERENTIAL DIAGNOSIS AND PREPARATION OF PATIENTS WITH LESIONS OF THE BILIARY TRACT. PMID- 17858034 TI - SPONTANEOUS INTERNAL BILIARY FISTULAE. PMID- 17858033 TI - VITALLIUM TUBES IN BILIARY SURGERY. PMID- 17858035 TI - REFLEXES ORIGINATING IN THE COMMON DUCT GIVING RISE TO PAIN SIMULATING ANGINA PECTORIS. PMID- 17858036 TI - CARCINOMA OF THE PANCREAS AND AMPULLARY REGION: REPORT OF SIX ADDITIONAL CASES. PMID- 17858037 TI - POSTOPERATIVE NITROGEN LOSS AND STUDIES ON PARENTERAL NITROGEN NUTRITION BY MEANS OF CASEIN DIGEST. PMID- 17858038 TI - CLINICAL AND EXPERIMENTAL STUDIES WITH THE KOCH METHOD OF TREATMENT OF HEAT BURNS. PMID- 17858039 TI - INFECTED BURNS WITH HEMORRHAGE. PMID- 17858040 TI - A SIMPLE METHOD FOR ESTIMATING PLASMA PROTEIN DEFICIT AFTER BURNS. PMID- 17858041 TI - RECENT TRENDS IN THE THERAPY OF BURNS. PMID- 17858043 TI - PROCUREMENT AND USE OF BLOOD SUBSTITUTES IN THE ARMY. PMID- 17858042 TI - LOCAL TREATMENT OF THERMAL BURNS. PMID- 17858044 TI - INTRAVENOUS INJECTIONS OF AMINO-ACIDS (HYDROLYZED CASEIN) IN POSTOPERATIVE PATIENTS. PMID- 17858045 TI - EPITHELIAL HEALING AND THE TRANSPLANTATION OF SKIN. PMID- 17858046 TI - SKIN REMOVAL IN RADICAL MASTECTOMY. PMID- 17858047 TI - TISSUE REACTION TO RIBBON CATGUT AND PRESERVED OX FASCIA LATA STRIPS. PMID- 17858048 TI - EFFECT OF ORCHIECTOMY AND IRRADIATION ON CANCER OF THE PROSTATE. PMID- 17858049 TI - NOTICE OF EDITION OF THE ANNALS OF SURGERY IN SPANISH. PMID- 17858050 TI - PRESIDENTIAL ADDRESS-DEFENSE OF THE HUMAN BODY AGAINST LIVING MAMMALIAN CELLS. PMID- 17858051 TI - REPORT TO THE AMERICAN SURGICAL ASSOCIATION ON THE ACTIVITIES OF DIVISION OF PROFESSIONAL SERVICE: UNDER THE SUPERVISION OF THE SURGEON-GENERAL OF THE U. S. ARMY. PMID- 17858052 TI - TRANSTHORACIC RESECTION OF TUMORS OF THE ESOPHAGUS AND STOMACH. PMID- 17858053 TI - PROBLEM OF INTESTINAL GASES COMPLICATING ABDOMINAL SURGERY. PMID- 17858054 TI - SMALL INTESTINE OBSTRUCTION: A FIVE-YEAR STUDY. PMID- 17858055 TI - VITAMIN DEFICIENCY AS A FACTOR IN THE ETIOLOGY OF SURGICAL DISEASES OF THE DIGESTIVE SYSTEM. PMID- 17858056 TI - APPENDICITIS IN INFANTS AND CHILDREN: A 15-YEAR STUDY. PMID- 17858057 TI - CLOSURE OF ILEOSTOMY IN ULCERATIVE COLITIS. PMID- 17858058 TI - EXPERIENCES WITH THE SURGICAL MANAGEMENT OF DIVERTICULITIS OF THE SIGMOID. PMID- 17858059 TI - SURGICAL TREATMENT OF MALIGNANT LESIONS OF THE SIGMOID-WITH EXTENSION. PMID- 17858060 TI - MECHANISM OF ACTION OF ROENTGENOTHERAPY UPON INFECTION. PMID- 17858061 TI - INVASION OF THE BONY PELVIS BY CARCINOMA OF THE CERVIX UTERI AS A CAUSE OF PATHOLOGIC CENTRAL DISLOCATION OF THE HIP. PMID- 17858062 TI - HEMORRHAGIC CYST OF THE SPLEEN. PMID- 17858063 TI - URINARY EXTRAVASATION (PERIURETHRAL PHLEGMON): A CLINICAL STUDY OF 32 CASES. PMID- 17858064 TI - EFFECT OF HEPARIN ON PHAGOCYTOSIS BY THE CELLS OF THE RETICULO-ENDOTHELIAL SYSTEM. PMID- 17858066 TI - BRIEF COMMUNICATIONS. PMID- 17858065 TI - CARDIOCIRCULATORY DYNAMICS IN SURGICAL SHOCK. PMID- 17858067 TI - PAGET'S DISEASE OF THE NIPPLE. PMID- 17858068 TI - HEMANGIOPERICYTOMA: A VASCULAR TUMOR FEATURING ZIMMERMANN'S PERICYTES. PMID- 17858069 TI - THE PATHOGENESIS OF MIXED TUMORS OF THE SALIVARY GLAND TYPE. PMID- 17858070 TI - ADENOLYMPHOMA OF THE PAROTID GLAND. PMID- 17858071 TI - ADRENAL-PRODUCING PHEOCHROMOCYTOMA OF THE ADRENAL ASSOCIATED WITH HYPERTENSION: REPORT OF THREE CASES. PMID- 17858072 TI - UROLOGIC COMPLICATIONS OF CANCER OF THE RECTUM. PMID- 17858073 TI - PHEOCHROMOCYTOMA WITH HYPERMETABOLISM: REPORT OF TWO CASES. PMID- 17858075 TI - MALIGNANT DEGENERATION OF NEUROFIBROMATA OF PERIPHERAL NERVE TRUNKS (VON RECKLINGHAUSEN'S DISEASE. PMID- 17858074 TI - SACROCOCCYGEAL TERATOID TUMOR: CASE REPORT. PMID- 17858076 TI - CANCER OF THE CERVICAL ESOPHAGUS. PMID- 17858077 TI - CYSTS OF THE SPLEEN. PMID- 17858078 TI - AN INTRAPERICARDIAL TERATOMA AND A TUMOR OF THE HEART: BOTH REMOVED OPERATIVELY. PMID- 17858079 TI - POSTOPERATIVE THROMBO-EMBOLIZATION: THE PLATELET COUNT AND THE PROTHROMBIN TIME AFTER SURGICAL OPERATIONS: A SIMPLE METHOD FOR DETECTING REDUCTIONS AND ELEVATIONS OF THE PROTHROMBIN CONCENTRATION (OR ACTIVITY) OF THE BLOOD PLASMA. PMID- 17858080 TI - THROMBOSIS AND GANGRENE OF RIGHT ARM, ASSOCIATED WITH POLYCYTHEMIA VERA: ITS RELATION TO "EFFORT THROMBOSIS". PMID- 17858081 TI - IMMEDIATE AND LATE RESULTS OF PERFORATION OF PEPTIC ULCER. PMID- 17858082 TI - THE LYMPHATIC AND VENOUS SPREAD OF CARCINOMA OF THE RECTUM. PMID- 17858083 TI - PRIMARY ABSCESS OF THE LIVER DUE TO ANAEROBIC NONHEMOLYTIC STREPTOCOCCUS. PMID- 17858084 TI - SEVERE TRAUMA TO THE LIVER WITH "HEPATORENAL SYNDROME". PMID- 17858085 TI - PLATYBASIA WITH INVOLVEMENT OF THE CENTRAL NERVOUS SYSTEM. PMID- 17858086 TI - EXTRALARYNGEAL DIVISION OF THE RECURRENT LARYNGEAL NERVE: ITS SIGNIFICANCE IN VOCAL CORD PARALYSIS. PMID- 17858087 TI - REPAIR OF DIRECT INGUINAL HERNIA WITH OSTEOPERIOSTEAL TRANSPLANT. PMID- 17858088 TI - UNUSUAL VISCERA IN INDIRECT INGUINAL HERNIAE. PMID- 17858090 TI - HEMISECTION OF THE MANDIBLE FOR RECURRENT ADAMANTINOMA. PMID- 17858089 TI - PRODUCTION OF A THROMBOTIC BARRIER IN THE TREATMENT OF VARICOSE VEINS. PMID- 17858091 TI - SO-CALLED DISLOCATION OF THE LOWER END OF THE ULNA. PMID- 17858093 TI - THE REGENERATION OF JOINT TRANSPLANTS AND INTRACAPSULAR FRAGMENTS. PMID- 17858092 TI - THE TREATMENT OF FRACTURES OF THE OLECRANON BY LONGITUDINAL SCREW OR NAIL FIXATION. PMID- 17858094 TI - BRIEF COMMUNICATIONS. PMID- 17858095 TI - INTESTINAL OBSTRUCTION IN THE NEWBORN. PMID- 17858096 TI - ATRESIA OF THE DUODENUM: CASE REPORT. PMID- 17858097 TI - MULTIPLE ATRESIA OF THE SMALL INTESTINE: CASE REPORT. PMID- 17858098 TI - A LARGE SUBACUTE GASTRIC ULCER: CASE REPORT. PMID- 17858099 TI - MULTIPLE, PRIMARY NONSPECIFIC JEJUNAL ULCERS, WITH CHRONIC DUODENAL DILATATION. PMID- 17858100 TI - MYO-EPITHELIAL HAMARTOMA OF THE ILEUM WITH INTUSSUSCEPTION. PMID- 17858101 TI - A STUDY OF THE BACTERIOLOGY OF THE COMMON BILE DUCT IN COMPARISON WITH THE OTHER EXTRAHEPATIC SEGMENTS OF THE BILIARY TRACT. PMID- 17858102 TI - ACUTE PANCREATITIS: REPORT OF TWENTY-NINE CASES. PMID- 17858103 TI - PULMONARY ABSCESS-A SURGICAL PROBLEM: CLASSIFICATION OF CASES AND DISCUSSION OF SURGICAL TREATMENT. PMID- 17858104 TI - CONTROL OF MASSIVE ESOPHAGEAL HEMORRHAGE SECONDARY TO LIVER DAMAGE (CIRRHOSIS) BY LIGATION OF THE CORONARY VEIN AND INJECTION OF SODIUM MORRHUATE. PMID- 17858105 TI - SLIDING AND OTHER LARGE BOWEL HERNIAE: DEVELOPMENT, CLASSIFICATION AND OPERATIVE MANAGEMENT. PMID- 17858106 TI - SPIGELIAN HERNIA: SPONTANEOUS LATERAL VENTRAL HERNIA THROUGH THE SEMILUNAR LINE. PMID- 17858107 TI - THE PREPARATION OF NONPYROGENIC INFUSION AND OTHER INTRAVENOUS FLUIDS BY ADSORPTIVE FILTRATION: REPORT OF 42 MONTHS' TRIAL. PMID- 17858108 TI - A SIMPLE METHOD OF PLASMA PROTEIN ESTIMATION. PMID- 17858109 TI - OBSERVATIONS ON THE FAILURE OF HEPARIN TO INHIBIT THE CLOTTING OF BLOOD IN VITRO BY STAPHYLOCOCCI. PMID- 17858111 TI - IMMEDIATE SKIN GRAFTING IN THE TREATMENT OF BURNS: A PRELIMINARY REPORT. PMID- 17858110 TI - DRAINAGE AND WOUND CLOSURE TECHNIQUE IN APPENDICITIS OPERATIONS. PMID- 17858112 TI - THE ELECTRO-ENCEPHALOGRAPHIC DIAGNOSIS OF SUBDURAL HEMORRHAGE. PMID- 17858113 TI - THE USE OF MYOTOMY IN THE REPAIR OF DIVIDED FLEXOR TENDONS. PMID- 17858114 TI - BRIEF COMMUNICATIONS. PMID- 17858115 TI - CLOSURE OF THE BRONCHUS FOLLOWING TOTAL PNEUMONECTOMY: EXPERIMENTAL AND CLINICAL OBSERVATIONS. PMID- 17858116 TI - THE EFFECT OF PNEUMONECTOMY UPON CARDIOPULMONARY FUNCTION IN ADULT PATIENTS. PMID- 17858118 TI - TRANSTHORACIC RESECTION OF TUMORS OF THE ESOPHAGUS AND STOMACH PART II. PMID- 17858117 TI - A PRACTICAL CONSIDERATION OF OPEN PNEUMOTHORAX UNDER SODIUM EVIPAL, SODIUM PENTOTHAL, AND ETHER ANESTHESIA. PMID- 17858119 TI - RECENT EXPERIENCES WITH THROMBOPHLEBITIS OF THE LOWER EXTREMITY AND PULMONARY EMBOLISM: THE VALUE OF VENOGRAPHY AS A DIAGNOSTIC AID. PMID- 17858120 TI - THE CONTROL OF HAIR AND FEATHER PIGMENTATION AS REVEALED BY GRAFTING MELANOPHORES IN THE EMBRYO. PMID- 17858121 TI - AN EXPERIMENTAL APPROACH TO THE PROBLEM OF MENSTRUAL DISORDERS. PMID- 17858122 TI - NEUROGENIC SHOCK: I. THE EFFECTS OF PROLONGED LOWERING OF BLOOD PRESSURE BY CONTINUOUS STIMULATION OF THE CAROTID SINUS IN DOGS. PMID- 17858123 TI - THE STADER REDUCTION SPLINT: FOR TREATING FRACTURES OF THE SHAFTS OF THE LONG BONES. PMID- 17858124 TI - BRIEF COMMUNICATION. PMID- 17858125 TI - A PRACTICAL CONCEPT FOR THE TREATMENT OF MAJOR AND MINOR BURNS: THE IMPORTANCE OF TIMING THEREIN. PMID- 17858126 TI - A STUDY OF THE "SHOCK-DELAYING" ACTION OF THE BARBITURATES: WITH A CONSIDERATION OF THE FAILURE OF OXYGEN-RICH ATMOSPHERES TO DELAY THE ONSET OF EXPERIMENTAL SHOCK DURING ANESTHESIA. PMID- 17858127 TI - CHEST INJURIES. PMID- 17858128 TI - PILONIDAL CYSTS AND SINUSES: A METHOD OF WOUND CLOSURE: REVIEW OF 230 CASES. PMID- 17858129 TI - SUCCESSFUL CLOSURE OF AN ARTERIOVENOUS ANEURYSM INVOLVING THE LEFT INNOMINATE VEIN AND THE LEFT COMMON CAROTID ARTERY. PMID- 17858130 TI - A COMPLICATED CASE OF ANEURYSM INVOLVING THE ILIAC AND FEMORAL ARTERIES. PMID- 17858131 TI - A COMPARISON OF THE RESULTS OF ROENTGEN RAYS, SULFANILAMIDE AND SERUM THERAPY IN EXPERIMENTAL GAS GANGRENE IN THE PIGEON. PMID- 17858132 TI - NONINFECTIVE GANGRENE FOLLOWING FRACTURES OF THE LOWER LEG. PMID- 17858133 TI - RECURRENT ULCERATION FOLLOWING SUBTOTAL GASTRECTOMY IN THE TREATMENT OF GASTRODUODENAL ULCER. PMID- 17858134 TI - PRIMARY CARCINOMA OF THE DUODENUM. PMID- 17858135 TI - SOLITARY NONPARASITIC CYST OF THE LIVER. PMID- 17858136 TI - STUDIES ON THE USE OF METALS IN SURGERY -PART II: EXPERIMENTS ON THE USE OF TICONIUM IN CRANIAL REPAIR. PMID- 17858137 TI - THE USE OF A LAMP TO WARM MOIST COMPRESSES. PMID- 17858138 TI - THE ANATOMIC APPROACH TO PULMONARY RESECTION. PMID- 17858139 TI - BRIEF COMMUNICATION: MEDIASTINAL GOITER. PMID- 17858141 TI - LYMPHEDEMA OF THE ARM FOLLOWING RADICAL MASTECTOMY FOR CARCINOMA OF BREAST: A NEW OPERATION FOR ITS CONTROL. PMID- 17858140 TI - CARCINOMA OF THE BREAST-PART I; RESULTS OF TREATMENT. PMID- 17858142 TI - EXTRADURAL HEMORRHAGE IN THE ANTERIOR CRANIAL FOSSA. PMID- 17858144 TI - TEMPORARY OCCLUSION OF THE PORTAL VEIN AND HEPATIC ARTERY: REPORT OF A SUCCESSFUL SUTURE OF AN INCISED PORTAL VEIN WITHIN THE LIVER. PMID- 17858143 TI - MASSIVE RUPTURE OF THE LIVER. PMID- 17858145 TI - POSTMORTEM PERITONEOSCOPY: A MEANS OF LEARNING PERITONEOSCOPY. PMID- 17858146 TI - ROLE OF INFECTION IN THE PATHOGENESIS OF LIVER NECROSIS IN HYPERTHYROIDISM. PMID- 17858147 TI - CRUVEILHIER-BAUMGARTEN SYNDROME (SPLENOMEGALY, PORTAL HYPERTENSION AND PATENT UMBILICAL VEIN): CASE REPORT. PMID- 17858148 TI - DUODENAL TUMOR OF UNUSUAL CHARACTER. PMID- 17858149 TI - VOLVULUS OF THE CECUM: REPORT OF FOUR CASES. PMID- 17858150 TI - LEIOMYOSARCOMA OF THE UTERUS. PMID- 17858151 TI - LESS COMMON LESIONS OF THE ASTRAGALUS. PMID- 17858152 TI - POSTERIOR PITUITARY EXTRACT IN ANESTHESIOLOGY. PMID- 17858153 TI - REGIONAL ILEITIS. PMID- 17858154 TI - INCREASING USEFULNESS OF THE DEVINE COLOSTOMY IN LEFT COLON AND RECTAL MALIGNANCY. PMID- 17858155 TI - METABOLIC STUDIES IN PATIENTS WITH CANCER OF THE GASTRO-INTESTINAL TRACT: VII-THE INFLUENCE OF GASTRIC SURGERY UPON THE CHEMICAL COMPOSITION OF THE LIVER. PMID- 17858156 TI - BRIEF COMMUNICATIONS. PMID- 17858157 TI - CLEFT PALATE. PMID- 17858158 TI - EMPYEMA COMPLICATED BY BRONCHO-ESOPHAGOPLEURAL FISTULA. PMID- 17858160 TI - SO-CALLED RETROPERITONEAL LIPOMA: REPORT OF SEVEN CASES. PMID- 17858159 TI - SUBSTITUTION OF THE URINARY BLADDER WITH A SEGMENT OF SIGMOID: AN EXPERIMENTAL STUDY. PMID- 17858161 TI - THE SURGICAL TREATMENT OF THE CONGENITAL MALFORMATIONS IMPLICATING THE DISTAL SPINAL CORD. PMID- 17858162 TI - THE TREATMENT OF CONGENITAL HEMANGIOMATA OF THE SKIN. PMID- 17858164 TI - A LIGHT COMPACT UNIT FOR THE INTRAVENOUS OR INTRAOSSEOUS INJECTION OF PLASMA IN EMERGENCIES. PMID- 17858163 TI - THE SURGICAL TREATMENT OF INTRINSIC KNEE JOINT LESIONS: FURTHER ANALYSIS OF OPERATIVE CASES. PMID- 17858165 TI - THE MECHANISM OF SHOCK IN INTESTINAL STRANGULATION: AN EXPERIMENTAL STUDY. PMID- 17858166 TI - FLUID, PROTEIN AND ELECTROLYTE ALTERATIONS IN EXPERIMENTAL INTESTINAL OBSTRUCTION. PMID- 17858167 TI - A STUDY OF PLASMA PROTEIN VARIATIONS IN SURGICAL PATIENTS. PMID- 17858168 TI - CARCINOMA OF THE GUM. PMID- 17858169 TI - RATE OF EPITHELIAL REGENERATION: A CLINICAL METHOD OF MEASUREMENT, AND THE EFFECT OF VARIOUS AGENTS RECOMMENDED IN THE TREATMENT OF BURNS. PMID- 17858170 TI - INTRATHORACIC NEUROBLASTOMA: CASE REPORT. PMID- 17858171 TI - THE SURGICAL TREATMENT OF TOPHACEOUS GOUT. PMID- 17858172 TI - TOTAL GASTRECTOMY FOR CANCER. PMID- 17858173 TI - PILONOIDAL CYST: THE LOCAL USE OF BUFFERED SULFANILAMIDE IN PRIMARY CLOSURE. PMID- 17858174 TI - BILIARY DYSKINESIA FROM THE SURGICAL VIEWPOINT. PMID- 17858175 TI - THE ADMINISTRATION OF MORPHINE AND ANTISPASMODICS IN BILIARY COLIC. PMID- 17858176 TI - MULTILOCULAR SEROUS CYSTS OF THE ROUND LIGAMENT SIMULATING INCARCERATED HERNIAE: REPORT OF THREE CASES. PMID- 17858177 TI - ACUTE APPENDICITIS DURING THE LATER DECADES OF LIFE: SOME REMARKS ON THE INCIDENCE OF THE DISEASE IN A RURAL AREA. PMID- 17858178 TI - THE PATHOLOGY OF BURNS: THE PATHOLOGIC PICTURE AS REVEALED AT AUTOPSY IN A SERIES OF 61 FATAL CASES TREATED AT THE HOSPITAL FOR SICK CHILDREN, TORONTO, CANADA. PMID- 17858179 TI - THE INTRA-ABDOMINAL USE OF THE MIKULICZ PACK. PMID- 17858181 TI - ECHINOCOCCUS CYST OF LUNG EXHIBITING UNUSUAL RADIOLOGIC AND SURGICAL FEATURES. PMID- 17858180 TI - REDUCTION OF THE MORTALITY IN THE SURGICAL MANAGEMENT OF HYPERTHYROIDISM: THE USE OF THE. SHORT INTERVAL TWO-STAGE LOBECTOMY. PMID- 17858182 TI - EVOLUTION OF SPINAL FUSION. PMID- 17858183 TI - STENOSING TENDOVAGINITIS AT THE RADIAL STYLOID (DeQUERVAIN'S DISEASE). PMID- 17858184 TI - TRENDS IN GENERAL SURGERY: REVIEW OF FIVE YEARS SURGICAL EXPERIENCE AT HARPER HOSPITAL. PMID- 17858185 TI - EARLY MORTALITY OF BURNS AS INFLUENCED BY RAPID TANNING AND BY TRANSFUSIONS. PMID- 17858186 TI - GOITER INCISIONS. PMID- 17858187 TI - THE PRE- AND POSTOPERATIVE EMPLOYMENT OF A BRASSTIPPED GASTRODUODENAL TUBE AS AN AID IN THE SURGICAL TREATMENT OF DUODENAL OBSTRUCTION IN THE NEWBORN. PMID- 17858188 TI - CONGENITAL CYSTIC DILATATION OF THE COMMON BILE DUCT : CASE REPORT AND REVIEW OF LITERATURE. PMID- 17858189 TI - THE INDICATIONS FOR JEJUNAL ALIMENTATION IN THE SURGERY OF PEPTIC ULCER. PMID- 17858190 TI - DIVERTICULA AND VARIATIONS OF THE DUODENUM. PMID- 17858192 TI - ACUTE ILEUS : ANALYSIS OF 130 CASES OPERATED UPON AT THE PRESBYTERIAN HOSPITAL, NEW YORK CITY, FROM 1936 TO 1939, INCLUSIVE: WITH USE OF MILLER-ABBOTT TUBE IN 1938 AND 1939. PMID- 17858191 TI - GASTROJEJUNOCOLIC FISTULAE: WITH SPECIAL REFERENCE TO ASSOCIATED NUTRITIONAL DEFICIENCIES AND CERTAIN SURGICAL ASPECTS. PMID- 17858193 TI - ISLET CELL CARCINOMA OF PANCREAS, WITH METASTASIS. PMID- 17858194 TI - CHOLESTEROSIS OF THE GALLBLADDER : OBSERVATIONS ON TWENTY-FIVE CASES WITHOUT STONES. PMID- 17858195 TI - LATE INVASION OF BLADDER AND PROSTATE IN CANCER OF THE RECTUM OR RECTO SIGMOID FOLLOWING ABDOMINO-PERINEAL RESECTION. PMID- 17858196 TI - COCHLIOMYIA AMERICANA INFESTATION IN MAN: CASE REPORT. PMID- 17858197 TI - CONTINUOUS CAUDAL ANALGESIA IN SURGERY. PMID- 17858198 TI - RESTORATION OF BLOOD FLOW IN DAMAGED ARTERIES: FURTHER STUDIES ON A NONSUTURE METHOD OF BLOOD VESSEL ANASTOMOSIS. PMID- 17858199 TI - THE INTRACTABLE DUODENAL ULCER : EVALUATION OF SURGICAL PROCEDURES. PMID- 17858200 TI - NITROGEN METABOLISM, CALORIC INTAKE AND WEIGHT LOSS IN POSTOPERATIVE CONVALESCENCE : A STUDY OF EIGHT PATIENTS UNDERGOING PARTIAL GASTRECTOMY FOR DUODENAL ULCERS. PMID- 17858201 TI - PREOPERATIVE SCRUBBING IN ABDOMINAL SURGERY-I. EXPERIMENTAL STUDIES. PMID- 17858202 TI - THE LATE EFFECTS OF CRANIOCEREBRAL INJURIES: A CONSIDERATION OF THE CRITERIA NECESSARY TO EVALUATE THE POSSIBLE CAUSES. PMID- 17858204 TI - FORENSIC ASPECTS OF BURNS: SPECIAL REFERENCE TO APPRAISAL OF TERMINAL DISABILITY. PMID- 17858203 TI - MECHANISMS OF HEAD INJURY. PMID- 17858205 TI - MINIMAL CRITERIA REQUIRED TO PROVE CAUSATION OF TRAUMATIC OR OCCUPATIONAL NEOPLASMS. PMID- 17858207 TI - THE RELATION OF TRAUMA TO DIABETES. PMID- 17858206 TI - MINIMAL CRITERIA REQUIRED TO PROVE PRIMA FACIE CASE OF TRAUMATIC ABORTION OR MISCARRIAGE : AN ANALYSIS OF 1000 SPONTANEOUS ABORTIONS. PMID- 17858208 TI - RELATION OF TRAUMA TO SYPHILIS OF THE NERVOUS SYSTEM. PMID- 17858209 TI - LOBECTOMY FOR PULMONARY TUBERCULOSIS. PMID- 17858210 TI - THE LOCAL EFFECT OF SULFANILAMIDE, SULFATHIAZOLE AND SULFADIAZINE UPON HEMOLYTIC STAPHYLOCOCCUS AUREUS INFECTIONS OF THE PLEURAL CAVITY. PMID- 17858211 TI - THE EFFECT OF SULFANILAMIDE, SULFATHIAZOLE AND SULFADIAZINE UPON THE PERITONEUM. PMID- 17858212 TI - PREVENTION OF SHOCK AND DEATH BY IMMEDIATE APPLICATION OF A PRESSURE DRESSING TO THE SEVERELY FROZEN LIMBS OF DOGS: AN EXPERIMENTAL STUDY. PMID- 17858213 TI - THE BLOOD CIRCULATION IN PEDICLE FLAPS : AN ACCURATE TEST FOR DETERMINING ITS EFFICIENCY. PMID- 17858215 TI - ATRESIA OF THE DUODENUM: A CASE SUCCESSFULLY TREATED BY DUODENODUODENOSTOMY. PMID- 17858214 TI - PERFORATED PEPTIC ULCER. PMID- 17858216 TI - CONGENITAL ATRESIA OF THE COMMON BILE DUCT: CASE REPORT. PMID- 17858217 TI - CYST OF THE AMPULLA OF VATER: CASE REPORT. PMID- 17858218 TI - HYPERESTHESIA OF THE POSTERIOR PERITONEUM IN APPENDICITIS AND OTHER VISCERAL LESIONS. PMID- 17858220 TI - THE TREATMENT OF POSTOPERATIVE HYPOPROTEINEMIA IN PATIENTS WITH CANCER OF THE COLON AND RECTUM. PMID- 17858219 TI - METABOLIC STUDIES IN PATIENTS WITH CANCER OF THE GASTRO-INTESTINAL TRACT. PMID- 17858221 TI - ACCESSORY SPLEEN IN THE SCROTUM: REVIEW OF LITERATURE ON ECTOPIC SPLEENS AND THEIR ASSOCIATED SURGICAL SIGNIFICANCE. PMID- 17858222 TI - SPONTANEOUS REPTURE OF THE URINARY BLADDER : REPORT OF CASE OF SECOND RUPTURE. PMID- 17858223 TI - PREOPERATIVE SCRUBBING IN ABDOMINAL SURGERY II-CLINICAL STUDIES. PMID- 17858224 TI - CLINICAL USES OF VITALLIUM. PMID- 17858225 TI - FOREWORD. PMID- 17858227 TI - SOCIAL SERVICE ACTIVITIES. PMID- 17858226 TI - THE PROBLEMS OF THE HOSPITAL ADMINISTRATION: I-THE COCOANUT GROVE DISASTER. PMID- 17858228 TI - NEUROPSYCHIATRIC OBSERVATIONS. PMID- 17858229 TI - RESUSCITATION AND SEDATION OF PATIENTS WITH BURNS WHICH INCLUDE THE AIRWAY: SOME PROBLEMS OF IMMEDIATE THERAPY. PMID- 17858231 TI - ROENTGENOLOGIC REPORT OF THE PULMONARY LESIONS. PMID- 17858230 TI - THE PULMONARY COMPLICATIONS: A CLINICAL DESCRIPTION. PMID- 17858232 TI - PATHOLOGY: WITH SPECIAL REFERENCE TO THE PULMONARY LESIONS. PMID- 17858233 TI - THE TREATMENT OF THE SURFACE BURNS. PMID- 17858234 TI - PROBLEMS OF INFECTION AND CHEMOTHERAPY. PMID- 17858236 TI - A NOTE ON PHYSICAL THERAPY. PMID- 17858235 TI - PROCEDURES IN REHABILITATION OF THE SEVERELY BURNED. PMID- 17858237 TI - THE PROBLEM OF BURN SHOCK COMPLICATED BY PULMONARY DAMAGE. PMID- 17858239 TI - A NOTE ON THE THROMBOPHLEBITIS ENCOUNTERED. PMID- 17858238 TI - A NOTE ON THE BLOOD BANK. PMID- 17858241 TI - PROTOCOLS. PMID- 17858240 TI - METABOLIC OBSERVATIONS. PMID- 17858242 TI - EXPERIENCES WITH BATTLE WOUNDS OF THE HEAD. PMID- 17858244 TI - RESULTS OF GALLBLADDER SURGERY IN DIABETES MELLITUS. PMID- 17858243 TI - INTESTINAL OBSTRUCTION DUE TO A GALLSTONE. PMID- 17858245 TI - ABSORBABLE COTTON, PAPER AND GAUZE : (OXIDIZED CELLULOSE). PMID- 17858246 TI - USE OF THROMBIN ON SOLUBLE CELLULOSE IN NEUROSURGERY: CLINICAL APPLICATION. PMID- 17858248 TI - ACUTE POSTOPERATIVE NECROSIS OF THE LIVER : AN EXPERIMENTAL STUDY. PMID- 17858247 TI - CONVULSIONS DURING GENERAL ANESTHESIA : REPORT OF TWELVE CASES. PMID- 17858249 TI - COMMUNICATIONS BETWEEN THE CORONARY ARTERIES PRODUCED BY THE APPLICATION OF INFLAMMATORY AGENTS TO THE SURFACE OF THE HEART. PMID- 17858250 TI - STAB WOUND OF THE HEART: CASE REPORT OF SUCCESSFUL SUTURE. PMID- 17858251 TI - THE SURGICAL MANAGEMENT OF SOLITARY CYSTS, OR CYST-LIKE STRUCTURES, OF PULMONARY ORIGIN. PMID- 17858252 TI - THE SPREAD OF CARCINOMA OF THE RECTUM: INVASION OF LYMPHATICS, VEINS AND NERVES. PMID- 17858253 TI - CHOLEDOCHUS CYST : FINAL REPORT OF TWO CASES. PMID- 17858254 TI - ROUTINE CYSTIC DUCT DRAINAGE FOLLOWING CHOLECYSTECTOMY. PMID- 17858255 TI - ADDRESS OF THE PRESIDENT-THE IMPORTANCE OF FUNDAMENTALS IN SURGICAL EDUCATION. PMID- 17858256 TI - THE STUDY OF THE PREVENTION OF INFECTION IN CONTAMINATED ACCIDENTAL WOUNDS, COMPOUND FRACTURES AND BURNS. PMID- 17858257 TI - BASIC PRINCIPLES IN THE TREATMENT OF THERMAL BURNS. PMID- 17858258 TI - GELATIN AS A PLASMA SUBSTITUTE WITH PARTICULAR REFERENCE TO EXPERIMENTAL HEMORRHAGE AND BURN SHOCK. PMID- 17858259 TI - PROBLEMS OF PROTEIN NUTRITION IN BURNED PATIENTS. PMID- 17858260 TI - AMINO-ACIDS, SERUM AND PLASMA IN THE REPLACEMENT THERAPY OF FATAL SHOCK DUE TO REPEATED HEMORRHAGE: AN EXPERIMENTAL STUDY. PMID- 17858261 TI - TRAUMATIC SHOCK: AN EXPERIMENTAL STUDY INCLUDING EVIDENCE AGAINST THE CAPILLARY LEAKAGE HYPOTHESIS. PMID- 17858262 TI - ROLE OF THE NERVOUS SYSTEM IN SHOCK. PMID- 17858263 TI - SURGICAL GUT CATGUT TUBING FLUID AS A TISSUE IRRITANT. PMID- 17858264 TI - HYDROCARBON CONTENT OF NONBOILABLE SURGICAL GUT TUBING FLUIDS. PMID- 17858265 TI - IRRITANT PROPERTIES OF TUBING FLUIDS AS A FACTOR IN THE TISSUE REACTIONS OBSERVED WITH SURGICAL GUT CATGUT. PMID- 17858266 TI - SURGICAL PRINCIPLES OPPOSED TO "RULE OF THE THUMB" IN THE TREATMENT OF COMPOUND FRACTURES. PMID- 17858267 TI - THE MEDICAL TREATMENT OF HEMATOGENOUS OSTEOMYELITIS. PMID- 17858268 TI - REGIONAL ILEITIS. PMID- 17858269 TI - METASTASIZING INTRACRANIAL TUMORS. PMID- 17858270 TI - CONSERVATION OF LUNG TISSUE BY PARTIAL LOBECTOMY. PMID- 17858271 TI - METABOLIC STUDIES IN PATIENTS WITH CANCER OF THE GASTRO-INTESTINAL TRACT : X HYPOPROTEINEMIA AND ANEMIA IN PATIENTS WITH GASTRIC CANCER. PMID- 17858272 TI - CONGENITAL DUODENAL OBSTRUCTION. PMID- 17858273 TI - NONMECKELIAN DIVERTICULA OF THE JEJUNUM AND ILEUM. PMID- 17858274 TI - DERMOID CYST OF PANCREAS: CASE REPORT. PMID- 17858275 TI - SPONTANEOUS RUPTURE OF LIVER COMPLICATING PREGNANCY. PMID- 17858276 TI - LIVER NECROSIS IN BURNS. PMID- 17858277 TI - ANIMAL EXPERIMENTS WITH TANNIC ACID: SUGGESTED BY THE TANNIC ACID TREATMENT OF BURNS. PMID- 17858279 TI - PILONIDAL SINUS: APPLICATION OF PLASTIC SURGICAL PRINCIPLES IN A NEW SURGICAL APPROACH. PMID- 17858278 TI - A CLINICAL TEST FOR DIFFERENTIATING SECOND FROM THIRD DEGREE BURNS. PMID- 17858280 TI - SYNOVIAL CYSTS OF THE POPLITEAL SPACE: CLINICAL SIGNIFICANCE AND TREATMENT. PMID- 17858281 TI - HEMANGIO-ENDOTHELIOMA: A TUMOR OF BLOOD VESSELS FEATURING VASCULAR ENDOTHELIAL CELLS. PMID- 17858282 TI - VENOUS HEMANGIOMA OF SKELETAL MUSCLE: CASE REPORT. PMID- 17858283 TI - VENOGRAPHY. PMID- 17858284 TI - A SUBCLAVIAN ANEURYSM CURED BY CELLOPHANE FIBROSIS. PMID- 17858286 TI - MANAGEMENT OF ULCERS AMONG NAVAL PERSONNEL. PMID- 17858285 TI - THE COAGULABILITY OF VENOUS BLOOD OF NORMAL AND DISEASED LEGS : A STUDY ON 191 SUBJECTS. PMID- 17858287 TI - EFFECTS OF PEDICLE GRAFTS OF JEJUNUM IN THE WALL OF THE STOMACH ON GASTRIC SECRETION : EXPERIMENTAL AND CLINICAL STUDIES. PMID- 17858288 TI - GASTRIC HISTOLOGY AND SUBTOTAL GASTRECTOMY. PMID- 17858289 TI - THE EFFECT ON GASTRIC ACIDITY OF GASTRO-ENTEROSTOMY AND GASTRIC RESECTION FOR PEPTIC ULCER. PMID- 17858290 TI - CHOLECYSTO-ENTEROSTOMY, CHOLEDOCHO-ENTEROSTOMY, AND ENTERO-ENTEROSTOMY BY MEANS OF RUBBER BANDS: THE USE OF RUBBER BANDS IN THE MIKULICZ OPERATION. PMID- 17858291 TI - SOME PHYSIOLOGIC PROBLEMS IN SURGERY OF THE PANCREAS. PMID- 17858293 TI - TOTAL PANCREATECTOMY FOR CARCINOMA : CASE REPORT. PMID- 17858292 TI - THE RECOGNITION AND MANAGEMENT OF ACUTE TRAUMA TO THE PANCREAS: WITH PARTICULAR REFERENCE TO THE USE OF THE SERUM AMYLASE TEST. PMID- 17858294 TI - EXPERIMENTAL STUDIES ON PERITONEAL ADHESIONS: FOURTH REPORT - SULFONAMIDES WITH AND WITHOUT HEPARIN. PMID- 17858296 TI - WAR WOUNDS OF THE CENTRAL NERVOUS SYSTEM. PMID- 17858295 TI - CHANGES IN BRAIN VOLUME AND BLOOD CONTENT AFTER EXPERIMENTAL CONCUSSION. PMID- 17858297 TI - RECENT ADVANCES IN THE TREATMENT OF RUPTURED LUMBAR INTERVERTEBRAL DISKS. PMID- 17858299 TI - ACUTE PUTRID ABSCESS OF THE LUNG : VII. RELATIONSHIP OF THE TECHNIC OF THE ONE STAGE OPERATION TO RESULTS. PMID- 17858298 TI - OBSERVATIONS ON THE DISTRIBUTION OF THE SYMPATHETIC NERVES TO THE PUPIL AND UPPER EXTREMITY AS DETERMINED BY STIMULATION OF THE ANTERIOR ROOTS IN MAN. PMID- 17858300 TI - THE CHOICE OF OPERATION FOR DELAYED AND NONUNION OF LONG BONES. PMID- 17858302 TI - SKIN REMOVAL IN RADICAL BREAST AMPUTATION. PMID- 17858301 TI - THYROCARDIAC DISEASE : A REVIEW OF 614 CASES. PMID- 17858303 TI - PILONIDAL CYSTS AND SINUSES. PMID- 17858304 TI - EFFECTS OF ETHER AND CYCLOPROPANE ANESTHESIA UPON THE RENAL FUNCTION IN MAN. PMID- 17858306 TI - PEROXIDE OINTMENTS. PMID- 17858305 TI - THROMBOSIS AND EMBOLISM : REVIEW OF 202 PATIENTS TREATED BY FEMORAL VEIN INTERRUPTION. PMID- 17858307 TI - EXPERIENCES OF A SURGICAL CONSULTANT OF A SERVICE COMMAND. PMID- 17858308 TI - THE SURFACE TREATMENT OF BURNS : A COMPARISON OF RESULTS OF TANNIC ACID, SILVER NITRATE, TRIPLE DYE, AND VASELINE OR BORIC OINTMENT AS SURFACE TREATMENTS IN 150 CASES. PMID- 17858309 TI - GUNSHOT WOUNDS OF THE ABDOMEN: A SURVEY OF 238 CASES. PMID- 17858310 TI - PRINCIPLES UNDERLYING THE OPERATIVE APPROACH TO THE TREATMENT OF MYOCARDIAL ISCHEMIA. PMID- 17858311 TI - CLINICAL APPRAISAL OF THE BECK OPERATION. PMID- 17858312 TI - TOTAL GASTRECTOMY BY THE TRANSTHORACIC APPROACH: REPORT OF SEVEN CASES. PMID- 17858313 TI - CARCINOMA OF THE DUODENUM. PMID- 17858314 TI - A NEW CONCEPT REGARDING THE ORIGIN OF SO-CALLED PRIMARY CARCINOMA OF THE HYPERPLASTIC THYROID. PMID- 17858315 TI - CARCINOMA OF THE BREAST: II. CRITERIA OF OPERABILITY. PMID- 17858316 TI - IMMEDIATE EFFECTS ON RENAL FUNCTION OF THE ONSET OF SHOCK DUE TO PARTIALLY OCCLUDING LIMB TOURNIQUETS. PMID- 17858317 TI - PRIMARY OSTEOGENIC SARCOMA OF THE BLADDER: COMPLETE REVIEW OF SARCOMATA OF THE BLADDER. PMID- 17858318 TI - MENINGIOMA: CASE REPORT. PMID- 17858319 TI - ANTERIOR SACRAL MENINGOCELE: REPORT OF THREE CASES. PMID- 17858320 TI - Partial Fundusectomy (Proximal Gastrectomy) : Review of 24 Cases. PMID- 17858321 TI - The Peptic Ulcer and Chronic Gastritis. PMID- 17858323 TI - Saphenous (Ligation) Resection in the Obese. PMID- 17858322 TI - Protein Metabolism and Bed Sores. PMID- 17858324 TI - Carcinoma of the Breast. II-Criteria of Operability. PMID- 17858325 TI - Amputation Neuroma in Nerves Implanted in Bone. PMID- 17858326 TI - Intravenous Gelatin. PMID- 17858327 TI - The Surgical Treatment of Malignant Lymphoma. PMID- 17858329 TI - Continuous Caudal Analgesia in Surgery. PMID- 17858328 TI - Planned Timing in the Treatment of Wounds and Infections by Means of Infrequent Occlusive Dressings. PMID- 17858330 TI - Advances in Spinal Anesthesia. PMID- 17858331 TI - Further Experiences with the Use of Adrenal Cortical Extract in Burn Shock. PMID- 17858332 TI - Use of One Flap to Restore Extensive Losses of the Middle Third of the Face. PMID- 17858333 TI - Experiences with Chest Wounds from the Pacific Combat Area. PMID- 17858334 TI - Lymphosarcoma of the Gastro-Intestinal Tract: Report of Twenty Cases. PMID- 17858335 TI - Hypertrophic Pyloric Stenosis in Adults: Report of Two Cases. PMID- 17858336 TI - Experiences in War Surgery in China. PMID- 17858337 TI - Afferent Vasodepressor Nerve Impulses as a Cause of Shock: Tested Experimentally by Aortic-Depressor Nerve Stimulation. PMID- 17858338 TI - Studies on Traumatic Shock: I. Blood Volume Changes in Traumatic Shock. PMID- 17858339 TI - Liposarcoma-the Malignant Tumor of Lipoblasts. PMID- 17858340 TI - A Report on the Management of Burns: Using the Occlusive Compression Dressing, with Sulfathiazole Emulsion. PMID- 17858341 TI - Refrigeration Anesthesia in Surgery. PMID- 17858342 TI - Regeneration of Pre- and Postganglionic Fibers Following Sympathectomy of the Upper Extremity: An Experimental Study. PMID- 17858343 TI - Total Pancreatectomy for Hyperinsulinism Due to an Islet-Cell Adenoma: Survival and Cure at Sixteen MOnths after Operation Presentation of Metabolic Studies. PMID- 17858344 TI - Total Gastrectomy, Splenectomy, Resection of the Left Lobe of the Liver, Omentumectomy and Colectomy on One Patient in One Operation. PMID- 17858345 TI - An Experiment in the Early Diagnosis of Gastric Carcinoma. PMID- 17858346 TI - The Frequency and Future of Gallstones Believed to be Quiescent or Symptomless. PMID- 17858347 TI - Preoperative Measures Used in War Surgery in China with Special Reference to the Delimiting Tourniquet. PMID- 17858348 TI - Cystomyoma of Seminal Vesicle. PMID- 17858349 TI - Teratoma of the Testicle -Metastasis to the Epigastrium Treated with Bilateral Orchidectomy. PMID- 17858350 TI - Compound Fracture of the Fingers. PMID- 17858351 TI - Regional Enteritis Involving Meckel's Diverticulum Perforation of the Diverticulum and Fistula Formation. PMID- 17858352 TI - Address of the President: Psychosomatic Surgery. PMID- 17858354 TI - Acute Perforation in Gastroduodenal Ulceration: With Special Reference to End Results. PMID- 17858353 TI - Indications for, and Experiences with, Total Gastrectomy: Based upon Seventy Three Cases of Total Gastrectomy. PMID- 17858355 TI - Carcinoma of the Duodenum: Report of Two Cases in Suprapapillary Portion. PMID- 17858356 TI - Congenital Pyloric Stenosis. PMID- 17858357 TI - Neurofibroma of the Small Intestine: Report of Case. PMID- 17858358 TI - Massive Resection of the Small Intestine: Report of Two Cases. PMID- 17858359 TI - Simple Penetrating Ulcer of the Cecum. PMID- 17858360 TI - Surgical Indications in Diseases of the Common Bile Duct. PMID- 17858361 TI - Cholesterolosis: Its Significance in the Badly Damaged Gallbladder. PMID- 17858362 TI - Combined Vascular and Nerve Injuries of Warfare. PMID- 17858363 TI - Control of Pain in Posttraumatic and Other Vascular Disturbances: The Role of the Sympathetic Nervous System in the Treatment of Peripheral Vascular Diseases. PMID- 17858364 TI - The Surgical Treatment of Experimental Coarctation (Atresia) of the Aorta. PMID- 17858365 TI - Ligation of the Abdominal Aorta for Aneurysm: Complicated by Rupture into the Retroperitoneal Space. PMID- 17858366 TI - The Technical Simplicity of the Matas Endo-aneurysmorrhaphy. PMID- 17858367 TI - Newer Aspects of Ruptured Intervertebral Disks. PMID- 17858368 TI - Spondylolisthesis : Analysis of Fifty-ninth Consecutive Cases. PMID- 17858369 TI - A Report on the Healing of Wounds as Influenced by the Use of the Sulfonamides and Cotton Thread Sutures. PMID- 17858371 TI - Clinical and Laboratory Experiences with Succinyl Sulfathiazole. PMID- 17858370 TI - The Chemotherapy of Intracranial Infections : Observations on the use of the Sulfonamides and of Penicillin under Various Experimental Intracranial Conditions. PMID- 17858372 TI - The Treatment of Burns Complicated by Fractures of the Extremities. PMID- 17858373 TI - Postoperative Salt Intolerance. PMID- 17858374 TI - Treatment of Metastatic Carcinoma of the Neck. PMID- 17858375 TI - Congenital Atresia of the Esophagus with Tracheo-Esophageal Fistulae : Transpleural Operative Approach. PMID- 17858376 TI - Chronic Cystic Mastitis: With Particular Reference to Classification. PMID- 17858377 TI - The Surgical Management of Cryptorchidism. PMID- 17858378 TI - Extraskeletal Osteogenic Sarcoma : Report of a Case of Osteogenic Sarcoma of the Lip. PMID- 17858379 TI - The Value of Nonprofit Blood Banks for Civilian Use: As Planned by the Office of Civilian Defense. PMID- 17858380 TI - Sir W. Arbuthnot Lane: 1856-1943. PMID- 17858381 TI - George Crile: 1864-1943. PMID- 17858383 TI - Mont Rogers Reid: 1889-1943. PMID- 17858382 TI - John Miller Turpin Finney: 1863-1942. PMID- 17858384 TI - Edward Joseph Ill: 1854-1942. PMID- 17858385 TI - Henry Dawson Furniss: 1878-1942. PMID- 17858386 TI - Robert Coalter Bryan: 1873-1941. PMID- 17858387 TI - Ross Arlington Woolsey: 1877-1942. PMID- 17858388 TI - Thomas Pinckney Waring: 1867-1943. PMID- 17858389 TI - Hermann Johannes Boldt: 1856-1943. PMID- 17858390 TI - Charles Watts Flynn, Jr: 1884-1943. PMID- 17858391 TI - Archibald Johnston Buist: 1873-1943. PMID- 17858392 TI - Granville S. Hanes: 1864-1943. PMID- 17858393 TI - Frank L. Barnes: 1872-1943. PMID- 17858394 TI - Surgical Lesions of the Facial Nerve: With Comments on its Anatomy. PMID- 17858395 TI - Diverticula of the Urinary Bladder. PMID- 17858396 TI - Thyroid Carcinoma With Metastases: Studied With Radioactive Iodine. PMID- 17858397 TI - Modified Technic in Skin Grafting of Extensive Deep Burns. PMID- 17858398 TI - Further Experience With the Treatment of Burns With Sulfonamide-Impregnated Membranes. PMID- 17858399 TI - Primary Hemangiomatous Tumors of Skeletal Muscle. PMID- 17858400 TI - Acute Retroperitoneal Abscess and Phlegmon : A Study of Sixty-five Cases. PMID- 17858401 TI - Annular Pancreas Producing Duodenal Obstruction : Report of a Successfully Treated Case. PMID- 17858402 TI - The Conservative Treatment of Acute Duodenal Fistula : Case Report. PMID- 17858403 TI - A Rare Abnormality of the Bile Ducts: The Anteduodenal Position of the Cystic Duct. PMID- 17858404 TI - Treatment of Horseshoe Kidneys. PMID- 17858405 TI - Wilms' Tumor in a Horseshoe Kidney : Case Report. PMID- 17858406 TI - Crude Penicillin: Its Preparation and Clinical Use Externally. PMID- 17858407 TI - Postoperative Chronic Progressive Gangrene of the Abdominal Wall. PMID- 17858408 TI - A Physiologic Analysis of the Nature and of the Treatment of Burns. PMID- 17858409 TI - The Nutritional Care of Cases of Extensive Burns : With Special Reference to the Oral Use of Amino-Acids (Amigen) in Three Cases. PMID- 17858410 TI - Adenomatosis of Islet Cells, With Hyperinsulinism. PMID- 17858411 TI - Pancreaticojejunostomy and Other Problems Associated With the Surgical Management of Carcinoma Involving the Head of the Pancreas: Report of Five Additional Cases of Radical Pancreaticoduodenectomy. PMID- 17858412 TI - Neurogenic Sarcoma of the Jejunum Associated with von Recklinghausen's Disease. PMID- 17858413 TI - Metabolic Studies in Patients With Cancer of the Gastro-intestinal Tract: XXII Estimation and Significance of Blood Loss during Gastro-intestinal Surgery. PMID- 17858414 TI - Enterogenous Cysts at the Ileocecal Junction. PMID- 17858415 TI - Differential Diagnosis of Causes of Pain in the Lower Back Accompanied by Sciatic Pain. PMID- 17858416 TI - An Anatomic Study of the Lumbosacral Region in Relation to Low Back Pain and Sciatica. PMID- 17858417 TI - Chronic Spinal Epidural Granuloma : Report of Two Cases. PMID- 17858418 TI - Venography: Its Value in the Diagnosis and Management of Venous Disturbances of the Lower Extremities. PMID- 17858419 TI - Pectus Excavatum: Report of Two Cases Successfully Operated Upon. PMID- 17858420 TI - Brachial Plexus Block Anesthesia: An Improved Technic. PMID- 17858421 TI - Basal Cell Lesions of the Nose, Cheek and Lips. PMID- 17858422 TI - Effect of Locally Implanted Sulfonamides on Wound Healing. PMID- 17858423 TI - Anesthetic Deaths in 54,128 Consecutive Cases. PMID- 17858424 TI - On the Removal of Enormous Vesical Calculi by the Suprapubic Route, with Report of a Successful Case. PMID- 17858425 TI - An Experimental Investigation into the Antiseptic Value of Iodoform. PMID- 17858426 TI - Contribution to Pulmonary Surgery. PMID- 17858427 TI - Contribution to the Study of Flat-Foot. PMID- 17858428 TI - The Treatment of Fractures of the Clavicle. PMID- 17858429 TI - New Method of Operating for Relief of Deformity from Prominent Ears. PMID- 17858430 TI - Recent British Contributions the the Surgery of Renal Calculi. PMID- 17858432 TI - Kroenlein on the Pathology and Operative Treatment of Dermoid Cysts of the Orbits. PMID- 17858431 TI - Czerny's Experiences with Resections of the Stomach and Intestines. PMID- 17858433 TI - INDEX OF SURGICAL PROGRESS. PMID- 17858434 TI - V. Downward Dislocation of the Patella. PMID- 17858435 TI - VI. The Pathology of Subluxation of the Head of the Radius in Children. PMID- 17858437 TI - INDEX OF SURGICAL PROGRESS. PMID- 17858436 TI - Results of Prostatectomy by the Suprapubic Route Obtained at the Leeds General Infirmary. PMID- 17858438 TI - I. Subdural Cerebral Abscess, and Subdural Cyst Relieved by Trephining. PMID- 17858439 TI - II. Interscaputo-Thoracic Amputation. PMID- 17858440 TI - III. Cirsoid Aneurism of Scalp. PMID- 17858442 TI - I. On the Symptoms of Chronic Obstruction of the Common Bile Duct by Gall Stones. PMID- 17858441 TI - IV. Miescher's Corpuscles in Actinomycosis. PMID- 17858443 TI - II. Recent Experience in the Diagnosis and Treatment of Cranial and Spinal Injuries. PMID- 17858444 TI - I. The Operative Treatment of Cancer of the Rectum. PMID- 17858445 TI - INDEX OF SURGICAL PROGRESS. PMID- 17858446 TI - I. The Operative Treatment of Talipes Calcaneus Paralyticus. PMID- 17858447 TI - II. A New Operation for Relief of Complete Prolapse of the Rectum. PMID- 17858449 TI - II. Recent American Contributions to the Treatment of Penetrating Wounds of the Abdomen. PMID- 17858448 TI - I. Rotter on Plastic Operations in the Cavity of the Mouth and on the Nose. PMID- 17858450 TI - INDEX OF SURGICAL PROGRESS. PMID- 17858451 TI - I. On Excision of the Superior Maxilla. PMID- 17858452 TI - II. On the Pathology and Treatment of Aggravated Haemorrhoids. PMID- 17858453 TI - III. On Symmetrical Manifestations of Syphilis. PMID- 17858454 TI - IV. Cases of Cuneiform Osteotomy for Relief of Double Congenital Equino-Varus. PMID- 17858455 TI - I. Delbet on Drainage of the Peritoneal Cavity. PMID- 17858456 TI - II. Darling on Carcinoma of the Bladder. PMID- 17858457 TI - III. Recent Contributions to the Operative Relief of Intracranial Conditions. PMID- 17858458 TI - IV. Lucas-Championniere on Massage and Mobilisation in the Treatment of Fractures. PMID- 17858459 TI - V. Jaffe on the Therapy of Habitual Scoliosis. PMID- 17858460 TI - INDEX OF SURGICAL PROGRESS. PMID- 17858462 TI - I. The Action of Chloroform in the Production of Anaesthesia, as Demonstrated by the Second Hyderabad Commission. PMID- 17858461 TI - I. On Penetrating Gunshot Wounds of the Abdomen. PMID- 17858464 TI - INDEX OF SURGICAL PROGRESS. PMID- 17858463 TI - II. Trendelenberg on Operations for Vesico-Vaginal Fistula, and on the Elevation of the Pelvis During Operations in the Pelvic Cavity. PMID- 17858465 TI - The Treatment of Air Force Combat Casualties. PMID- 17858466 TI - Whole Upper Extremity Transplant for Human Beings: General Plans of Procedure and Operative Technic. PMID- 17858468 TI - Operation for Aneurysm of the Heart. PMID- 17858467 TI - Studies on the Effects of Posture in Shock and Injury. PMID- 17858469 TI - Infected Dissecting Aneurysm of the Iliac Artery Following Arteriovenous Fistula of the Femoral Vessels. PMID- 17858470 TI - Ligation of the Abdominal Aorta: Case Report. PMID- 17858472 TI - Primary Gastric Resection for Perforated Gastroduodenal Ulcers. PMID- 17858471 TI - Surgical Aspects of Pancreatic Fistula. PMID- 17858473 TI - Atresia of Small Intestine; Two Case Reports; One Multiple Atresia, With Survival. PMID- 17858474 TI - Cauda Equina Compression Syndrome With Herniated Nucleus Pulposus: A Report of Eight Cases. PMID- 17858475 TI - Lumbosacral Roentgenograms of 450 Consecutive Applicants for Heavy Work. PMID- 17858476 TI - Comparative Values of Various Methods of Resuscitation. PMID- 17858477 TI - Studies on Surgical Convalescence I-Sources of Nitrogen Loss Postgastrectomy and Effect of High Amino-Acid and High Caloric Intake on Convalescence. PMID- 17858478 TI - Continuous Spinal Anesthesia Observations on 2000 Cases. PMID- 17858479 TI - Continuous Spinal Anesthesia For Labor and Delivery. A Preliminary Report. PMID- 17858480 TI - The Use of Thiouracil in the Preparation of Patients With Hyperthyroidism for Thyroidectomy. PMID- 17858482 TI - Hemostasis With Absorbable Gauze (Oxidized Cellulose). PMID- 17858481 TI - Subtotal Gastrectomy for Duodenal Ulcer. PMID- 17858483 TI - Leiomyoma of the Jejunum: Intermittent Melena of Fourteen Years Duration, and Fatal Hemorrhage. PMID- 17858484 TI - Retrograde Jejunogastric Intussusception Through a Subtotal Gastrectomy Stoma. PMID- 17858485 TI - The Influence of Ether, Morphine and Nembutal on Mortality in Experimental Burns. PMID- 17858486 TI - Closure of Defects of Lips With Composite Vermilion Border-Lined Flaps. PMID- 17858487 TI - Dupuytren's Contracture: Fibroma of the Palmar Fascia. PMID- 17858488 TI - Omental Circulation in Morphinized Dogs Subjected to Graded Hemorrhage. PMID- 17858489 TI - Condylomata Acuminata: Two Hundred Cases Treated With Podophyllin. PMID- 17858490 TI - The State of the Association. PMID- 17858491 TI - The Surgical Management of the Wounded in the Mediterranean Theater at the Time of the Fall of Rome-[Foreword by Brig. Gen'l Fred W. Rankin, M.C.]. PMID- 17858492 TI - Vascular Injuries of Warfare. PMID- 17858493 TI - The Use of Penicillin in Surgical Infections. PMID- 17858494 TI - Acute Starvation Following Operation or Injury: With Special Reference to Caloric and Protein Needs. PMID- 17858495 TI - The Healing of Deep Thermal Burns: A Preliminary Report. PMID- 17858497 TI - A Comparison of Various Types of Local Treatment in a Controlled Series of Experimental Burns in Human Volunteers. PMID- 17858496 TI - A Study of the Interrelationship of Salt Solutions Serum and Defibrinated Blood in the Treatment of Severely Scalded, Anesthetized Dogs. PMID- 17858498 TI - Tannic Acid and the Treatment of Burns: An Obsequy. PMID- 17858499 TI - The Surgical Treatment of Carcinoma of the Body of the Pancreas. PMID- 17858501 TI - Refrigerated Skin Grafts. PMID- 17858500 TI - The Repair of Surface Defects of the Foot. PMID- 17858502 TI - Skin Graft Fixation by Plasma-Thrombin Adhesion. PMID- 17858503 TI - The Influence of Sulfonamides on Postoperative Complications. PMID- 17858504 TI - Chronic Constrictive Pericarditis: Partial Pericardiectomy and Epicardiolysis in Twenty-Four Cases. PMID- 17858505 TI - The Problem of Embolism of the Pulmonary Artery: Report of a Transcardiac Operation. PMID- 17858506 TI - Effect of Sulfonamides Upon Experimental Gunshot Wounds Involving Peripheral Nerves. PMID- 17858507 TI - Thiouracil in the Preparation of Thyrotoxic Patients for Surgery. PMID- 17858508 TI - The Relationship of Protein Deficiency to Surgical Infection. PMID- 17858509 TI - Emergency Gastrectomy for Acute Perforation of Carcinoma of the Stomach, With Diffuse Soiling of the Free Peritoneal Cavity. PMID- 17858511 TI - Closure of Colonic Stoma: Improved Results With Combined Succinylsulfathiazole and Sulfathiazole Therapy. PMID- 17858510 TI - Complications and Mortality in Subtotal Gastrectomy for Duodenal Ulcer: Report on a Two-Stage Procedure. PMID- 17858512 TI - The Advantages and Disadvantages of Closed Resection of the Colon. PMID- 17858513 TI - Large Melena of Obscure Origin. PMID- 17858514 TI - Inflammatory Stricture of the Rectum: An Analysis of 192 Cases, Including 35 Treated by Rectosigmoid Resection. PMID- 17858515 TI - Influence of Estrogens on the Peripheral Vasomotor Mechanism. PMID- 17858516 TI - Modification of the King Operation for Bilateral Vocal Cord Paralysis. PMID- 17858517 TI - Congenital Atresia of the Esophagus With Tracheoesophageal Fistula : Reconstruction of Esophageal Continuity by Primary Anastomosis. PMID- 17858518 TI - The Danger and Prevention of Citrate Intoxication in Massive Transfusions of Whole Blood. PMID- 17858520 TI - Effects of Bovine Anterior Hypophyseal Extract on Urinary Bladder Transplants in Young Dogs. Including Some Observations on its Effects on Endochondral Ossification. PMID- 17858519 TI - Surgical Manifestations of Coccidioidomycosis. PMID- 17858521 TI - Experimental Study of the Histopathology of Burns With Particular Reference to Sites of Fluid Loss in Burns of Different Depths. PMID- 17858522 TI - Experimental Study of the Tannic Acid Treatment of Burns: With Particular Reference to Its Effect on Local Fluid Loss and Healing. PMID- 17858523 TI - Refrigeration in Clinical Surgery. PMID- 17858524 TI - Effects of Cooling on Experimentally Infected Tissues. PMID- 17858525 TI - The Effect of Cooling on Wound Healing. PMID- 17858526 TI - Nerve Degeneration Following Prolonged Cooling of an Extremity. PMID- 17858527 TI - Hyperinsulinism Treated by Subtotal Pancreatectomy. PMID- 17858528 TI - Stellate Ganglion Block: A New Anterior Approach. PMID- 17858529 TI - Congenital Atresia of the Esophagus: With Tracheo-Esophageal Fistula. PMID- 17858530 TI - Varicose Veins: Anatomic Findings and an Operative Procedure Based Upon Them. PMID- 17858531 TI - An Improved Method for Collecting, Centrifuging and Pooling Blood Plasma. PMID- 17858532 TI - The Peripheral Circulation During the Tourniquet Shock Syndrome in the Rat. PMID- 17858533 TI - Proposed Alteration in the Knee Joint of Prosthesis for Below-Knee Amputation. PMID- 17858534 TI - The Racial Distribution of Cancer II. Tumors of the Kidney, Bladder and Male Genital Organs. PMID- 17858535 TI - Wounds of the Heart. PMID- 17858536 TI - The Beneficial Effect of Intravenous Infusions in Acute Pericardial Temponade. PMID- 17858537 TI - Synovial Sarcoma. PMID- 17858538 TI - Synovial Sarcoma and Normal Synovial Tissue Cultivated in Vitro. PMID- 17858539 TI - Physiologic Observations on Patients With External Pancreatic Fistula. PMID- 17858540 TI - The Healing of Surface Cutaneous Wounds: Its Analogy With the Healing of Superficial Burns. PMID- 17858542 TI - Urinary Complications of Pelvic Endometriosus. PMID- 17858541 TI - Battle Casualties in a South Pacific Evacuation Hospital. PMID- 17858543 TI - An Application of Staging in the Removal of Difficult Wilms' Tumors. PMID- 17858545 TI - Resplitting Split-Thickness Grafts With the Dermatome. A Method for Increasing the Yield of Limited Donor Sites. PMID- 17858544 TI - External Pin Transfixion of Fractures: An Analysis of 80 Cases. PMID- 17858546 TI - Portal Vein Thrombosis Following Removal of Ruptured Spleen. PMID- 17858547 TI - Roentgenologic Examination of the Abdomen as an Aid in the Early Diagnosis of Splenic Injury. PMID- 17858548 TI - Sulfonamide Therapy in Clean Thoracoplasty Cases. PMID- 17858549 TI - Curling's Ulcer in Experimental Burns. PMID- 17858550 TI - Comparative Studies of Cancerous Versus Noncancerous Breasts. PMID- 17858551 TI - Transthoracic Esophagogastrostomy for Carcinoma of the Middle Third of the Esophagus. Report of a Successful Resection. PMID- 17858552 TI - The Effect of Chemotherapy on the Ileum Subjected to Vascular Injury. PMID- 17858553 TI - Diverticulitis of the Cecum: A Method of Management. PMID- 17858554 TI - Multiple Polypoid Disease of the Colon and Rectum. PMID- 17858556 TI - Secondary Suture of War Wounds: A Clinical Study of 305 Secondary Closures. PMID- 17858555 TI - Craniocerebral War Wounds: Observations on Delayed Treatment. PMID- 17858557 TI - Refrigeration Anesthesia and Evaluation of Amputation Sites by Arteriogram. PMID- 17858559 TI - Skin Graft of Dorsum of Hand: Use of Large size Dermatome to Obtain One-Piece Pattern. PMID- 17858558 TI - The Biopsy as an Accurate Guide to the Decision of Early Skin Grafting. PMID- 17858560 TI - Proximal Ligation and Thrombectomy for Phlebothrombosis of the Femoral and Iliac Veins. PMID- 17858561 TI - The Economic Value of Periotoneoscopy. PMID- 17858562 TI - Spontaneous Intra-abdominal Hemorrhage. PMID- 17858563 TI - Comparative Studies of Cancerous Versus Noncancerous Breasts. PMID- 17858564 TI - Studies in Surgical Convalescence: A Preliminary Study of the Nitrogen Loss in Exudates in Surgical Conditions. PMID- 17858565 TI - The Effects of Temperature on the Digestion of Collagen Sutures and Surgical Gut (Catgut) by Enzymes and by the Subcutaneous Tissues of the Frog. PMID- 17858566 TI - The Submucosal Morcellation of Hemorrhoids. PMID- 17858567 TI - Albright's Syndrome: Report of a Case Associated with Multiple Pathologic Fractures, Disseminated Fibrous Dysplasia of Bones, Precocious Puberty and Multiple Pigmented Nevi. PMID- 17858568 TI - Report on Immersion Foot Casualties From the Battle of Attu. PMID- 17858569 TI - Transthoracic Resection of the Esophagus and Stomach for Carcinoma : Analysis of the Postoperative Complications, Causes of Death, and Late Results of Operation. PMID- 17858570 TI - Selection of the Time for Grafting of Skin to Extensive Defects Resulting from Deep Thermal Burns. PMID- 17858571 TI - The Influence of Local Treatment of Burns on Liver Function. PMID- 17858572 TI - Studies on the Toxemia Syndrome After Burns II: Central Nervous System Changes as a Cause of Death. PMID- 17858574 TI - Wheal Fluorescence: A New Method of Evaluating Peripheral Vascular Diseases. PMID- 17858573 TI - The Problem of Thrombophlebitis. PMID- 17858575 TI - Pooled Human Serum. PMID- 17858577 TI - Malignant Granular Cell Myoblastoma Involving the Urinary Bladder. PMID- 17858576 TI - Plasma Volume, "Available (Thiocyanate) Volume" and Total Circulating Plasma Proteins in Normal Adults. PMID- 17858578 TI - The Treatment of Actinomycosis With Penicillin. PMID- 17858580 TI - Treatment of Carcinoma of the Colon. PMID- 17858579 TI - Address of the President: Whither Anon. PMID- 17858581 TI - A Method of Re-establishing Continuity between the Bile Ducts and the Gastro Intestinal Tract. PMID- 17858583 TI - A Nonsuture Method of Blood Vessel Anastomosis : Review of Experimental Study Report of Clinical Cases. PMID- 17858582 TI - Primary Carcinoma of the Gallbladder : An Additional Reason for Early Removal of the Calculous Gallbladder. PMID- 17858584 TI - End-Results in the Treatment of Hyperparathyroidism. PMID- 17858585 TI - Cases of Severe Pelvic Injury. PMID- 17858586 TI - Studies on Traumatic Shock: V: The Treatment of Clinical Shock with Gelatin. PMID- 17858588 TI - Heparin in the Abdomen : A Clinical Report. PMID- 17858587 TI - Pentothal-Metrazol Antagonism : A Method of Shortening the Recovery Period Following Pentothal Anesthesia a Clinical and Experimental Study. PMID- 17858589 TI - Methods of Constructing a Vagina. PMID- 17858590 TI - Spontaneous Perforation of the Rectovaginal Septum, Five Weeks after Construction of the Vagina : Case Reports. PMID- 17858591 TI - Intervertebral Disk Lesions are the Most Common Cause of Low Back Pain with or Without Sciatica. PMID- 17858592 TI - Current Considerations of War Surgery. PMID- 17858594 TI - An Emergency Surgical Plan in an Army Air Force Hospital. PMID- 17858593 TI - Remarks on a Few Surgical Problems in Aviation Medicine. PMID- 17858595 TI - An Analysis of the Results of the Surgical Treatment of 260 Consecutive Cases of Chronic Peptic Ulcer of the Duodenum. PMID- 17858596 TI - Transthoracic Gastrectomy for Unusual Lesions of the Stomach. PMID- 17858597 TI - A Plan for the Surgical Management of Gastrojejunocolic Fistula. PMID- 17858598 TI - Full-Thickness Skin Grafts from the Neck for Function and Color in Eyelid and Face Repairs. PMID- 17858599 TI - Tattooing of Free Skin Grafts and Pedicle Flaps. PMID- 17858601 TI - Penicillin as an Adjunct to the Surgical Treatment of Acute and Chronic Empyemas. PMID- 17858600 TI - Tantalum Cranioplasty for War Wounds of the Skull. PMID- 17858602 TI - Total Hysterectomy. PMID- 17858604 TI - Observations on the Conversion of Normal into Malignant Cells. PMID- 17858603 TI - Surgical Principles Underlying the Use of Grafts in the Repair of Peripheral Nerve Injuries. PMID- 17858605 TI - Mucoid Disease of the Appendix. PMID- 17858606 TI - Appendicitis: The Possible Effects of Sulfonamides on Mortality. PMID- 17858607 TI - Sacral and Presacral Tumors. PMID- 17858608 TI - Treatment of Varicose Veins by Stripping, Excision and Evulsion. PMID- 17858609 TI - Quadricepsplasty. PMID- 17858611 TI - Edward Peirson Richardson: 1881-1944. PMID- 17858610 TI - Herrmann Bertram Gessner: 1872-1944. PMID- 17858612 TI - Kenneth Hazen Aynesworth: 1873-1944. PMID- 17858614 TI - Preparation of Battle Casualties for Surgery. PMID- 17858613 TI - William Simpson Elkin: 1858-1944. PMID- 17858615 TI - Graduate Surgical Training in America. PMID- 17858616 TI - Local Fluid Loss, Nerve Stimuli and Toxins in the Causation of Shock. PMID- 17858617 TI - Stainless Steel Wire-Mesh in the Repair of Small Cranial Defects. PMID- 17858618 TI - Fracture of the Atlas: Review and Presentation of Data on Eight Cases. PMID- 17858619 TI - Chest Wounds in Battle Casualties. PMID- 17858620 TI - The Problem of Massive Hemorrhage from Duodenal Ulcers of Patients Beyond Middle Life: With Particular Reference to the Value of the Devine Exclusion Operation in Selected Cases of this Nature. PMID- 17858621 TI - Pancreaticoduodenectomy for Islet Carcinoma : A Five-Year Follow-Up. PMID- 17858622 TI - Suppurative Pancreatitis with Associated Liver Abscess. PMID- 17858623 TI - Frozen Human Skin Grafts. PMID- 17858625 TI - Bone Sarcoma in Polyostotic Fibrous Dysplasia. PMID- 17858624 TI - The Pyruvic Acid Method of Burn Slough Removal: An Experimental Investigation. PMID- 17858626 TI - Spontaneous Rupture of Axillary Artery. PMID- 17858627 TI - An Unusual Case of Meckel's Diverticulum. PMID- 17858629 TI - Traumatic Aneurysm of the First Portion of the Left Vertebral Artery: Case Report. PMID- 17858628 TI - Traumatic Osteomyelitis: The Use of Skin Grafts-Part I: Technic and Result. PMID- 17858631 TI - Serum Amylase Findings in Chronic Alcoholic Patients with Acute, Severe Abdominal Symptoms. PMID- 17858630 TI - Stricture of the Female Urethra with Lymphopathia Venerea: Lymphogranuloma Inguinale. PMID- 17858632 TI - Experiences with 156 Penetrating Wounds of the Head. PMID- 17858633 TI - Myoblastoma: Case Report. PMID- 17858634 TI - Experiences with Injuries and Diseases of Bone in World War II. PMID- 17858635 TI - Experiences with Sympathectomy in Peripheral Lesions. PMID- 17858637 TI - Cholecystogastroduodenocutaneous Biliary Fistula: Case Report. PMID- 17858636 TI - Resurfacing of Dorsum of the Hand Following Burns. PMID- 17858638 TI - Solitary Diverticulitis of the Cecum: Report of two Cases. PMID- 17858639 TI - A Continuous Traction Screw for Fixation of Fractures of the Hip: Review of 23 Cases. PMID- 17858641 TI - The Present Status of the Injection Treatment of Hernia. PMID- 17858640 TI - Recurrent Inguinal Hernia. PMID- 17858642 TI - Cancer of the Face: A Clinical and Statistical Study of 1062 Cases. PMID- 17858643 TI - Observations on the Severely Wounded in Forward Field Hospitals: With Special Reference to Wound Shock. PMID- 17858644 TI - Evacuation Hospital Experiences with War Wounds and Injuries of the Chest: A Preliminary Report. PMID- 17858646 TI - Traumatic Right Diaphragmatic Hernia: Case with Delayed Herniation of the Liver and Gallbladder. PMID- 17858645 TI - Early Pulmonary Decortication in the Treatment of Posttraumatic Empyema. PMID- 17858647 TI - The Value of Antitoxin in the Prevention and Treatment of Malignant Edema and Gas Gangrene : A Review of Observations. PMID- 17858648 TI - The Immediate and Late Treatment of an Arteriovenous Fistula. PMID- 17858649 TI - Arterial Injuries in a Theater of Operations. PMID- 17858651 TI - Experiences with the Miller-Abbott Tube : A Statistical Study of 1000 Cases. PMID- 17858650 TI - Chronic Hypertrophic Antrum Gastritis. PMID- 17858652 TI - The Surgical Significance of an Anomalous Cholecystohepatic Duct: Case Reports. PMID- 17858654 TI - Coma During and Following Spinal Anesthesia. PMID- 17858653 TI - Complications of Intra-Osseous Therapy. PMID- 17858655 TI - Reparative Surgery of Compound Battle Fractures in the Mediterranean Theater of Operations. PMID- 17858656 TI - The Management of Intrathoracic and Thoraco-abdominal Wounds in the Combat Zone. PMID- 17858657 TI - Combined Injuries of the Thorax and Abdomen. PMID- 17858658 TI - Compound, Comminuted Skull Fractures Produced by Missiles: Report Based upon 100 Cases. PMID- 17858659 TI - The Surgical Management of Colon and Rectal Injuries in the Forward Areas. PMID- 17858660 TI - The Management of War Injuries of the Extraperitoneal Rectum. PMID- 17858661 TI - The Simultaneous Occurrence of Acute Appendicitis and Malaria. PMID- 17858662 TI - Right Paraduodenal Hernia. PMID- 17858663 TI - Benign Capillary Hemangioma of Digital Flexor Tendon Sheath : Case Report. PMID- 17858665 TI - The Technic of Using Vitallium Tubes in Establishing Portacaval Shunts for Portal Hypertension. PMID- 17858664 TI - The Problem of Portal Hypertension in Relation to the Hepatosplenopathies. PMID- 17858666 TI - The Use of Vitallium Tubes in Strictures and Absence of the Common Bile Duct. PMID- 17858667 TI - Advanced Carcinoma of the Extrahepatic Bile Ducts: Choleangiocholecystocholedochectomy. PMID- 17858668 TI - Arteriovenous Aneurysm : Exposure of the Tibial and Peroneal Vessels by Resection of the Fibula. PMID- 17858669 TI - The Surgical Treatment of the More Common Type of Diaphragmatic Hernia : Report of 404 Cases. PMID- 17858670 TI - Congenital Diaphragmatic Hernia. PMID- 17858671 TI - Idiopathic Dilatation of the Esophagus : Differentiation of Clinical Types and Successful Operation in Intractable Cases. PMID- 17858672 TI - Congenital or Hereditary Polyposis of the Colon. PMID- 17858673 TI - The Local Use of Sulfanilamide in the Treatment of Acute Appendicitis : A Review of 1481 Cases. PMID- 17858674 TI - Secondary Hemorrhage Arising from Gunshot Wounds of the Peripheral Blood Vessels. PMID- 17858675 TI - Secondary Infection of Wounds. PMID- 17858676 TI - Traumatic Shock Incurable by Volume Replacement Therapy : A Summary of Further Studies including Observations on the Hemodynamics, Intermediary Metabolism and Therapeutics of Shock. PMID- 17858677 TI - Translocation of Fluid Produced by the Intravenous Administration of Isotonic Salt Solutions in Man Postoperatively. PMID- 17858678 TI - Metabolic Alterations Following Thermal Burns: V. The use of Whole Blood and an Electrolyte Solution in the Treatment of Burned Patients. PMID- 17858679 TI - The Rationale of Whole Blood Therapy in Severe Burns : A Clinical Study. PMID- 17858680 TI - Direct Flap Repair of Defects of the Arm and Hand : Preparation of Gunshot Wounds for Repair of Nerves, Bones and Tendons. PMID- 17858681 TI - A Design for Surgical Convalescence. PMID- 17858682 TI - Profits to Peace-time Practice from Surgical Experiences of War. PMID- 17858683 TI - A Study of Shock in Battle Casualties: Measurements of the Blood Volume Changes Occurring in Response to Therapy. PMID- 17858684 TI - A Comparative Study of 100 Fractures of the Shaft of the Femur in Which One-Half were Treated with Penicillin. PMID- 17858685 TI - Thoraco-Abdominal Injuries: A Report of Twenty-Nine Operated Cases. PMID- 17858686 TI - Anesthesia for Men Wounded in Battle. PMID- 17858688 TI - Regional Enteritis. PMID- 17858687 TI - Muco-Epidermoid Tumors of Salivary Glands. PMID- 17858689 TI - The Second Five-Year Period Experience in Total Thyroidectomy. PMID- 17858691 TI - Observations on the Surgical Treatment of Hernia. PMID- 17858690 TI - Ainhum (Dactylolysis Spontanea): Report of Two Cases from Illinois. PMID- 17858692 TI - The Use of Heterogenous Fascial Grafts in the Radical Operation for Herniae. PMID- 17858693 TI - Renal Decapsulation for Transfusion Oliguria. PMID- 17858694 TI - The Use of Fluorescent Wheals in Determining Extent and Degree of Peripheral Vascular Insufficiency: Further Observations. PMID- 17858695 TI - The Pathogenesis of Localized Fibrous Lesions in the Metaphyses of Long Bones. PMID- 17858696 TI - Bilateral Adrenalectomy in Prostatic Cancer: Clinical Features and Urinary Excretion of 17-Ketosteroids and Estrogen. PMID- 17858697 TI - Subtotal Replacement of the Skin of the Face: For Actinodermatitis Due to Roentgenotherapy: with Multiple Areas of Squamous Cell Carcinoma. PMID- 17858698 TI - Congenital Cataracts Following Rubella in Pregnancy. PMID- 17858700 TI - Osteomyelitis of the Petrous Pyramid of the Temporal Bone. PMID- 17858699 TI - Headaches from Lesion of Scalp Nerves. PMID- 17858701 TI - The Present Status of Ethylene-Oxygen Anesthesia. PMID- 17858703 TI - Resection of the Left Lobe of the Liver in a Patient with Four Separate Carcinomas. PMID- 17858702 TI - Acoustic Trauma. PMID- 17858704 TI - The Etiology and Treatment of Polycythemia Rubra Vera : Observations Based upon Studies of Body Fluid Changes in Dogs Subjected to Proprioceptor Depressor Neurotomy and Extensive Sympathectomy, Including the Case Report of a Man with Polycythemia Rubra Vera Treated by Extensive Para-Vertebral Sympathectomy. PMID- 17858705 TI - Principles and Practice of Penicillin Therapy in Diseases of the Nervous System. PMID- 17858707 TI - Acute Hypertension with Sodium Pentothal Anesthesia in Neurologic Surgery. PMID- 17858706 TI - Traumatic Rupture of the Spleen. PMID- 17858708 TI - The Use of Blood Plasma for Filling the Pleural Space Following Total Pneumonectomy : A Clinical Study. PMID- 17858709 TI - Chronic Leptomeningeal Thickening Following Treatment of Meningitis with Sulfa drugs. PMID- 17858711 TI - Surgical Relief of Tremor at Rest. PMID- 17858710 TI - Radical Resections of Advanced Intra-abdominal Cancer: Summary of Results in 100 Patients. PMID- 17858712 TI - Transthoracic Esophagogastrostomy for Benign Strictures of the Lower Esophagus. PMID- 17858713 TI - The Use of Penicillin in the Treatment of Acute Hematogenous Osteomyelitis in Children: Report of Twelve Consecutive Cases. PMID- 17858714 TI - Blood Iodine Studies : VII. The Relation of the Basal Metabolic Rate to the Blood Iodine in Thyroid Disease. PMID- 17858715 TI - Vagotomy for Gastroduodenal Ulcer. PMID- 17858716 TI - Blood Pressure of Renal and of Early and Late Neurogenic Hypertension Dogs after Low Cervical Cord Section. PMID- 17858717 TI - Cutis Grafts: Clinical and Experimental Studies on their use as a Reinforcing Patch in the Repair of Large Ventral and Incisional Herniae. PMID- 17858718 TI - Delayed Internal Fixation of Compound Battle Fractures in the Mediterranean Theater of Operations: A Follow-up Study in the Zone of Interior. Part I. PMID- 17858719 TI - Retroperitoneal (Mesenteric Pouch) Hernia: Case Report. PMID- 17858720 TI - Cystic Disease of the Liver: Report of a Case. PMID- 17858721 TI - Congenital Cystic Dilatation of the Common Bile Duct: Follow-up on Previously Reported Case and Report of Additional Case. PMID- 17858722 TI - Traumatic Rupture of the Gallbladder: Case Reports and Notes on Choleperitoneum. PMID- 17858724 TI - Extradural Spinal Hemorrhage. PMID- 17858723 TI - Sarcoma Complicating Paget's Disease of Bone. PMID- 17858725 TI - The Incidence of Complications in the Use of Transfixion Pins and Wires For Skeletal Traction. PMID- 17858726 TI - Abdominal Surgery in an Evacuation Hospital. PMID- 17858727 TI - Chemotherapy in Traumatic Surgery of the Abdomen. PMID- 17858728 TI - Lung Abscess Complicating Penetrating Wounds of the Chest. PMID- 17858729 TI - The Operative Treatment of Decubitus Ulcer. PMID- 17858730 TI - The Role of Chemotherapy in Wounds and Surgical Infections: I-Clinical and Bacteriologic Studies. PMID- 17858731 TI - Pain in Men Wounded in Battle. PMID- 17858732 TI - Vascular Injuries of the Extremities in Battle Casualties. PMID- 17858733 TI - Penetrating Head Wounds: Experiences from the Italian Campaign. PMID- 17858734 TI - Treatment of Jaw and Face Casualties in the British Army. PMID- 17858735 TI - Repair of Soft-tissue War Wounds. PMID- 17858737 TI - Congenital Cystic Lung: Successful Pneumonectomy in a Three-Week-Old Baby. PMID- 17858736 TI - Pulmonary Embolism: A Statistical Study: With Particular Reference to the Value of Certain Preventive Measures. PMID- 17858738 TI - Delayed Internal Fixation of Compound Battle Fractures in the Mediterranean Theater of Operations, Part II: Case Histories with Illustrations a Follow-Up Study in the Zone of Interior. PMID- 17858740 TI - Biliary Ascariasis: Report of 19 Cases. PMID- 17858739 TI - The Surgical Significance of the Accessory Spleen. PMID- 17858741 TI - Sympathectomy for Ischemia Following Femoral Artery Ligation. PMID- 17858742 TI - Battle Wounds of the Thoracic Cavity. PMID- 17858743 TI - The "Wet Lung" in War Casualties. PMID- 17858744 TI - Penetrating Wounds of the Chest. PMID- 17858745 TI - Thoracic Gastric Cyst. PMID- 17858746 TI - Results Following Bands and Ligatures on the Human Internal Carotid Artery. PMID- 17858747 TI - Gastric Retention after Posterior Gastro-Enterostomy for Duodenal Ulcer: Prevention and Treatment. PMID- 17858748 TI - The So-Called "Dumping Syndrome" after Subtotal Gastrectomy: A Clinical Study. PMID- 17858749 TI - Postappendicectomy Interstitial Inguinal Hernia. PMID- 17858750 TI - Aneurysm of Hepatic Artery. PMID- 17858751 TI - Reflex Vasodilatation in Tubed Pedicle Skin Grafts. PMID- 17858752 TI - Rhabdomyosarcoma of the Skeletal Muscles. PMID- 17858754 TI - Address of the President: The Transylvania Medical Library. PMID- 17858753 TI - Supracondylar Amputations: A Survey. PMID- 17858755 TI - Newer Concepts in the Treatment of the Paralyzed Patients Due to War-Time Injuries of the Spinal Cord : Outline of Plan and Statistical Analysis. PMID- 17858756 TI - Newer Concepts in the Treatment of the Paralyzed Patient Due to War-Time Injuries of the Spine: Neurosurgical Complications. PMID- 17858757 TI - Methods of Closure of Decubitus Ulcers in the Paralyzed Patient. PMID- 17858759 TI - Traumatic Arteriovenous Fistula Involving the Abdominal Aorta and the Inferior Vena Cava. PMID- 17858758 TI - Battle Injuries of the Arteries in World War II : An Analysis of 2,471 Cases. PMID- 17858760 TI - Cirsoid Aneurysm of the Scalp : Report of Four Cases. PMID- 17858761 TI - The Management of Aneurysms of the Lower Extremities. PMID- 17858762 TI - Plastic Surgery in World War I and in World War II. PMID- 17858763 TI - Use of Cancellous Bone in the Repair of Defects About the Jaws. PMID- 17858764 TI - Muscle-flap Transplant for the Relief of Painful Monarticular Arthritis (Aseptic Necrosis) of the Hip. PMID- 17858765 TI - Fixation of Tendons, Ligaments and Bone by Bunnell's Pull-out Wire Suture. PMID- 17858766 TI - Muscle Flap Closure of Cavity Resulting From Lung Abscess. PMID- 17858767 TI - Dyschondroplasia. PMID- 17858768 TI - Traumatic Osteomyelitis: The Use of Skin Grafts-Part II : Subsequent Treatment. PMID- 17858770 TI - Repair of Surface Defects of the Upper Extremity. PMID- 17858769 TI - Repair of Bony Defects Associated with Osteomyelitis. PMID- 17858771 TI - Experiences with Early Nerve Surgery in Peripheral Nerve Injuries. PMID- 17858773 TI - Angiomatous Malformations of the Brain : Successful Extirpation in Three Cases. PMID- 17858772 TI - Mediastinal Tumors : Report of Cases Treated at Army Thoracic Surgery Centers in the United States. PMID- 17858774 TI - An Analysis of Brain Abscesses Observed During the Past Thirty Years. PMID- 17858775 TI - Craniotomy and Total Dissection as a Method in the Treatment of Abscess of the Brain. PMID- 17858776 TI - Streptomycin in Urinary Infections. PMID- 17858777 TI - A New Method for Constructing an Artificial Esophagus. PMID- 17858779 TI - Indications for and Value of Choledochoduodenostomy. PMID- 17858778 TI - Experiences in Subtotal Resection of the Pancreas in Hypoglycemia. PMID- 17858780 TI - Malignant Tumors of the Small Bowel. PMID- 17858781 TI - Restoration of Continuity after Resection of the Rectum. PMID- 17858782 TI - Further Observations Upon Imperforate Anus. PMID- 17858783 TI - Congenital Defect of the Abdominal Wall in the Newborn : (Gastroschisis). PMID- 17858784 TI - Fortyeight Consecutive Cases of Gangrenous Suppurative Appendictis, with Removal of the Appendix and Complete Closure of the Wound, without a Death. PMID- 17858786 TI - The Prevention and Treatment of Postoperative Lymphedema of the Arm. PMID- 17858785 TI - An Investigation of the Role of Chemotherapy in Wound Management in the Mediterranean Theater. PMID- 17858787 TI - Refrigeration Anesthesia for Amputation. PMID- 17858789 TI - The Treatment of Sebaceous Cyst by Electrosurgical Marsupialization. PMID- 17858788 TI - Vertical Traction: An Aid in the Surgical Management of Certain Large Tumors : Case Report. PMID- 17858790 TI - Robert Tuttle Morris: 1857-1945. PMID- 17858791 TI - Robert DuVal Jones: 1898-1945. PMID- 17858792 TI - Gerry Rounds Holden: 1874-1945. PMID- 17858793 TI - William Farquhar Shallenberger: 1881-1944. PMID- 17858794 TI - The Surgical Treatment of Funnel Chest. PMID- 17858795 TI - The Use of Testosterone Propionate in the Treatment of Advanced Carcinoma of the Breast. PMID- 17858796 TI - Coincident Removal of Additional Structures in Resections for Carcinoma of the Colon and Rectum. PMID- 17858798 TI - Repeated Massive Intestinal Hemorrhage: Report of an Unusual Case. PMID- 17858797 TI - Choledochus Cyst. PMID- 17858799 TI - Neurofibroma of the Small Intestine with Massive Hemorrhage. PMID- 17858800 TI - Adenolymphoma of the Parotid and Submaxillary Salivary Glands. PMID- 17858801 TI - Pilonidal Cysts and Sinuses: A Technic for Excision and Primary Closure. PMID- 17858802 TI - Basic Principles in Geriatric Surgery. PMID- 17858803 TI - Wound Healing with Low Vitamin C Level. PMID- 17858804 TI - Exarticulation of the Lower Extremities for Malignant Tumors. PMID- 17858805 TI - Chest Wounds in Battle Casualties. PMID- 17858806 TI - Thoraco-abdominal Wounds without Abdominal Signs: Report of Two Cases. PMID- 17858807 TI - Wounds of the Urinary Bladder: An Analysis of 155 Cases. PMID- 17858808 TI - Exarticulation of the Lower Extremities for Malignant Tumors: Hip Joint Disarticulation (with and without Deep Iliac Dissection) and Sacro-iliac Disarticulation (Hemipelvectomy) Part III. PMID- 17858809 TI - A Two-Stage Mastopexy in Plastic Surgery of Markedly Enlarged Breasts. PMID- 17858810 TI - A Minute Granulosa Cell Tumor, with Vaginal Bleeding. PMID- 17858811 TI - Streptococcus Viridans Septicemia from Vegetations in Femoral Arteriovenous Aneurysm: Report of a Case Cured by Surgical Excision of the Aneurysm. PMID- 17858812 TI - The Influence of a Special High Protein Diet on Protein Regeneration in the Surgical Patient. PMID- 17858813 TI - Absorbable Gauze in Bone Surgery : Experimental Studies Suggesting Clinical Application in Reconstruction of Joints. PMID- 17858814 TI - Management of Late Head Injuries. PMID- 17858815 TI - The Technic of Immediate Restoration of Vascular Continuity after Arterial Wounds: Indications and Results. PMID- 17858816 TI - Reconstruction of the Thumb. PMID- 17858817 TI - Cervical Rib: The Role of the Clavicle in Occlusion of the Subclavian Artery. PMID- 17858818 TI - Resection of the Left Lobe of the Liver for Mesenchymoma: Report of Case. PMID- 17858819 TI - Postoperative Atelectasis and Pneumonia: Diagnosis, Etiology and Management Based upon 1,240 Cases of upper Abdominal Surgery. PMID- 17858820 TI - Experience with Curare in Anesthesia. PMID- 17858821 TI - Thiouracil in the Treatment of Thyrotoxicosis: Experience of the Thyroid Clinic of the Columbia-Presbyterian Medical Center. PMID- 17858822 TI - Early Postoperative Ambulation. PMID- 17858823 TI - The Effect of Evisceration upon Traumatic Abdominal Wounds. PMID- 17858824 TI - Orthopedic Surgery in the European Theater of Operations: A Brief Resume. PMID- 17858825 TI - Laminectomy for Pott's Paraplegia. PMID- 17858826 TI - Indications and Results of Surgery of the Autonomic Nervous System in Naval Personnel. PMID- 17858827 TI - Granular Cell Myoblastoma of the Mammary Gland. PMID- 17858828 TI - Combined Roentgen Radiation and Surgical Treatment of Large Benign Giant Cell Tumors of Bone. PMID- 17858830 TI - Cushing's Syndrome. PMID- 17858829 TI - Epithelioma of the Anus. PMID- 17858831 TI - Acute Intussusception in Infants and Children. PMID- 17858832 TI - Prevention of Wound Infection by the Injection of Nontoxic Antibacterial Substances. PMID- 17858833 TI - A Study in Articular Replacement. PMID- 17858834 TI - An Approach to Resections of the Esophagus and Gastric Cardia. PMID- 17858835 TI - A Report on Trench Foot and Cold Injuries in the European Theater of Operations: 1944-1945. PMID- 17858836 TI - War-time Activities of the National Research Council and the Committee on Medical Research: With Particular Reference to Team-work on Studies of Wounds and Burns. PMID- 17858837 TI - The Effect of Pentothal Sodium on Mean Arterial Blood Pressure in the Presence of High Spinal Cord Paralysis. PMID- 17858838 TI - The Importance of Whole Blood Transfusions in the Management of Severe Burns. PMID- 17858840 TI - Massive Pancreatic Hemorrhage : Case Report. PMID- 17858839 TI - Lesions of the Musculotendinous Cuff of the Shoulder: III. Observations on the Pathology, Course and Treatment of Calcific Deposits. PMID- 17858841 TI - War Injuries of the Chest. PMID- 17858842 TI - Notes on Operative Technic in Neurosurgery. PMID- 17858843 TI - Posterior Cordotomy for Relief of Phantom Limb Pain. PMID- 17858844 TI - Streptomycin in Surgical Infections: II. Infections of the Genito-urinary Tract. PMID- 17858846 TI - Displacement of Medial Epicondyle of Humerus into the Elbow Joint. PMID- 17858845 TI - Antral Gastritis and Spasm: Their Clinical and Surgical Significance. PMID- 17858847 TI - A Technic for Combined Measurement of Motility and Electric Action Potentials in the Human Intestine. PMID- 17858848 TI - The Treatment of Compound Fractures in the Italian Campaign. PMID- 17858849 TI - Gunshot Wounds of the Abdomen. PMID- 17858850 TI - Skin-grafting the Burned Dorsum of the Hand. PMID- 17858851 TI - The Thoraco-abdominal Casualty. PMID- 17858853 TI - Congenital Stenosis of Small Intestine: With Retention of Nonpenetrating Foreign Bodies: Report of two Cases. PMID- 17858852 TI - Perforated Gastroduodenal Ulcers: A Study of 166 Cases. PMID- 17858854 TI - Familial Diverticulosis of the Colon: Report of Seven Cases in one Family of Nine Persons. PMID- 17858855 TI - Carcinoma of Meckel's Diverticulum: Case Report. PMID- 17858856 TI - Enterogenous Cysts: Report of Case Involving the Rectum. PMID- 17858858 TI - Splenectomy: Removal of a Spleen Weighing 5,450 Grams. PMID- 17858857 TI - Liposarcoma of the Mesentery. PMID- 17858859 TI - Surgical Treatment for Dysphagia Lusoria. PMID- 17858860 TI - Pulmonary Actinomycosis: Its Treatment by Pulmonary Resection in Conjunction with Chemotherapy. Report of two Cases. PMID- 17858861 TI - Management of Injuries to Stensen's Duct. PMID- 17858862 TI - Mastectomy for Gynecomastia Through a Semicircular Intra-areolar Incision. PMID- 17858864 TI - Incisions in Surgery of Aneurysms: With Special Reference to Exploration in the Anticubital and Popliteal Fossae. PMID- 17858863 TI - Subtrochanteric Osteotomy for Ununited Fracture Neck of the Femur. PMID- 17858865 TI - Cross Nerve Anastomosis in Man. PMID- 17858866 TI - Address of the President: Treatment of Fractures. PMID- 17858867 TI - Pharyngo-esophageal Diverticulum: Its Management and Complications. PMID- 17858869 TI - Carcinoma of the Midthoracic Esophagus : Its Treatment by Radical Resection and High Intrathoracic Esophagogastric Anastomosis. PMID- 17858868 TI - Diverticula of the Lower Thoracic Esophagus : Report of Six, Four of which were Operated upon. PMID- 17858870 TI - Bronchiogenic Carcinoma. PMID- 17858871 TI - Palliative Gastrectomy in Selected Cases of Gastric Ulcer. PMID- 17858872 TI - Subtotal Gastrectomy for Duodenal Ulcer. PMID- 17858873 TI - Congenital Hypertrophic Pyloric Stenosis. PMID- 17858874 TI - Late Results in the Treatment of Ulcerative Colitis. PMID- 17858875 TI - Diverticulitis of the Colon. PMID- 17858876 TI - Resection of Abdominal Carcinomas Involving the Liver and Spleen Secondarily. PMID- 17858877 TI - Definitive Surgery of the Large Intestine Following War Wounds. PMID- 17858878 TI - Early Ambulation in Abdominal Surgery. PMID- 17858879 TI - The Pyruvic Acid Method in Deep Clinical Burns. PMID- 17858880 TI - The Anemia of Thermal Burns. PMID- 17858881 TI - Ascorbic Acid, Riboflavin, Thiamin, and Nicotinic Acid in Relation to Severe Injury, Hemorrhage, and Infection in the Human. PMID- 17858883 TI - The Surgical Treatment of Congenital Pulmonic Stenosis. PMID- 17858882 TI - The Treatment of Acute Renal Failure by Peritoneal Irrigation. PMID- 17858884 TI - Arterial Repair in the Treatment of Aneurysms and Arteriovenous Fistulae : A Report of Eighteen Successful Restorations. PMID- 17858885 TI - Roentgenologic Kymographic Studies of the Heart in the Presence of an Arteriovenous Fistula and their Interpretation. PMID- 17858886 TI - Arteriovenous Aneurysm of the Vertebral Vessels : Report of Ten Cases. PMID- 17858888 TI - Penicillin in the Treatment of Established Surgical Infections : A Systematic Study of 744 Including 82 Septicemias. PMID- 17858887 TI - Studies on the Use of Gelatin Sponge or Foam as an Hemostatic Agent in Experimental Liver Resections and Injuries to Large Veins. PMID- 17858889 TI - The Clinicians' Responsibility in the Teaching of Surgery. PMID- 17858890 TI - Pancreatitis as a Cause of Complete Obstruction of the Common Duct. PMID- 17858892 TI - Tetanus-A Preventable Disease : Including an Experience with Civilian Casualties in the Battle for Manila (1945). PMID- 17858891 TI - Results from using Vitallium Tubes in Biliary Surgery. PMID- 17858893 TI - Surgical Treatment of Angina Pectoris : Experiences with Ligation of the Great Cardiac Vein and Pericoronary Neurectomy. PMID- 17858895 TI - The New Viewpoint toward Spinal Cord Injuries. PMID- 17858894 TI - Management and Rehabilitation of Naval Battle Casualty Amputees. PMID- 17858896 TI - Operative Results in Intervertebral Disks. PMID- 17858897 TI - Penetrating Wounds of the Chest in the Pacific Area: An Analysis of 180 Cases. PMID- 17858898 TI - Fractures of the Os Calcis : Their Treatment by Tri-Radiate Traction and Subastragalar Fusion. PMID- 17858899 TI - Composite Free Grafts of Two Surfaces of Skin and Cartilage from the Ear. PMID- 17858900 TI - Unusual Surgical Lesions of the Umbilicus : Report of Cases of Congenital Origin. PMID- 17858901 TI - Studies on the Effects of Adult Animal Tissue Extracts on Wound Healing: A Preliminary Report of the Factors Responsible. PMID- 17858902 TI - Primary Closure of Bedsores by Plastic Surgery. PMID- 17858903 TI - The Primary Closure of Decubitus Ulcers. PMID- 17858904 TI - Studies on Nutrition : The Effect of Preoperative Force-Feeding on Surgical Patients. PMID- 17858905 TI - Radical Surgery for Certain Cases of Pancreatic Fibrosis associated with Calcareous Deposits. PMID- 17858906 TI - Expeditious Care of Full-Thickness Burn Wounds by Surgical Excision and Grafting. PMID- 17858907 TI - Experimental Observations on Absorbable Alginate Products in Surgery : Gel, Film, Gauze and Foam. PMID- 17858908 TI - Nutritional Rehabilitation of Surgical Patients. PMID- 17858909 TI - A Technic for Testing Hypertensive Patients Preoperatively. PMID- 17858910 TI - Esophageal Atresia and Tracheo-esophageal Fistula. PMID- 17858911 TI - Pulsion Diverticulum of the Pharyngo-esophageal Junction: Technic of the One stage Operation: A Preliminary Report. PMID- 17858912 TI - Anatomic Data Regarding the Surgical Treatment of Angina Pectoris. PMID- 17858913 TI - A Ten-year Survey of Intestinal Obstruction. PMID- 17858914 TI - Traumatic Pancreatitis. PMID- 17858915 TI - The Surgical Treatment of 1,545 Herniae. PMID- 17858917 TI - Experiences with Posttraumatic Osteomyelitis in World War II. PMID- 17858916 TI - Scalenotomy: An Analysis of Eleven Cases Done for Scalenus Anticus Syndrome. PMID- 17858918 TI - Bone Grafting Methods: Two Illustrative Case Reports. PMID- 17858919 TI - The Use of Shunt or By-pass Operations in the Treatment of Certain Circulatory Disorders, including Portal Hypertension and Pulmonic Stenosis. PMID- 17858920 TI - Thoracic Surgery in a Hospital Center: Part I. PMID- 17858921 TI - War Experiences with the Nonsuture Technic of Anastomosis in Primary Arterial Injuries. PMID- 17858922 TI - Phenylpropanolamine Hydrochloride: A Vasopressor Drug, for Maintaining Blood Pressure during Spinal Anesthesia. PMID- 17858923 TI - The Effect of the Local Reduction of Temperature on Scald Burns in the Rat. PMID- 17858924 TI - Streptomycin in Surgical Infections: I-Laboratory Studies. PMID- 17858925 TI - Sympathectomy in Trench Foot. PMID- 17858926 TI - Congenital Dislocation of the Hip. PMID- 17858927 TI - Autogenous Diced Cartilage Transplants to Bone: An Experimental Study. PMID- 17858928 TI - Experimental Carcinoma of the Gallbladder : Supplementary Data. PMID- 17858929 TI - The Surgical Therapeutic Significance of the Functional Behavior of Thyroid Nodules. PMID- 17858931 TI - The Mechanism of Hemostasis. PMID- 17858930 TI - Malignant Adenoma of the Thyroid, with Secondary Metastases to Bone: With a Discussion of So-Called "Benign Metastasizing Goiter". PMID- 17858932 TI - Thoracic Surgery in a Hospital Center: Part II. PMID- 17858933 TI - The Modern Technic of the Le Fort Operation. PMID- 17858934 TI - Compound Injuries of the Knee Joint : Study I. PMID- 17858935 TI - The Treatment of Peripheral Nerve Injuries Complicated by Skin and Soft Tissue Defects. PMID- 17858936 TI - The Use of Radioactive Sodium in the Study of Peripheral Vascular Disease. PMID- 17858937 TI - The Value of External Skeletal Fixation in Elective Orthopedic Surgery. PMID- 17858938 TI - Compound Injuries of the Knee Joint : Study II-The Infected Knee Joint. PMID- 17858939 TI - Surgical Management of Gunshot Wounds of the Pelvic Viscera and Their Late Complications. PMID- 17858940 TI - Studies on the Acid DeBridement of Burns. PMID- 17858941 TI - Extremity Refrigeration without Tourniquet Ligation in Cases of Acute Arterial Deficit. PMID- 17858942 TI - Primary Fibrosarcoma of the Liver. PMID- 17858943 TI - Simultaneous Repair of Peripheral Nerve and Soft Tissue Defects in the Forearm. PMID- 17858944 TI - Bacteriologic Study of Burn Wounds : A Comparison of the Bacterial Flora of Burn Wounds of Patients Treated with Sulfonamides or Penicillin. PMID- 17858945 TI - The Mortality of Surgical Disease. PMID- 17858947 TI - The Present Status of the Surgical Treatment of Carcinoma of the Lung. PMID- 17858946 TI - Primary Pulmonary Malignancy Treated by Resection: An Analysis of 129 Cases. PMID- 17858948 TI - A Concept of Toxic Goiter. PMID- 17858949 TI - The Use of Thiouracil, Thiobarbital and Propyl thiouracil in Patients with Hyperthyroidism. PMID- 17858950 TI - Use of Thyroid Extract with Thiouracil in the Preparation of the Thyrotoxic Patient : A Preliminary Report. PMID- 17858951 TI - An Evaluation of Pulmonary Embolism following Intravascular Venous Thrombosis. PMID- 17858952 TI - The Study of Malignant Cells with Phase Difference Microscopy. PMID- 17858953 TI - Surgical Considerations in the Treatment of Hypertension. PMID- 17858954 TI - Chronic Shock: The Problem of Reduced Blood Volume in the Chronically Ill Patient In Three Parts. PMID- 17858955 TI - The Treatment of Injuries of the Brachial Plexus. PMID- 17858956 TI - Should the Neck Nodes be Dissected in Patients with Carcinoma of the Lip? PMID- 17858957 TI - The Present Status of the Leg Length Discrepancy Problem. PMID- 17858958 TI - Analysis of Pelvic Operations Preceding Hysterectomy: Causal Relationship. PMID- 17858959 TI - Carcinoma of the Breast: A Study of 298 Consecutive Cases. PMID- 17858960 TI - Carcinoma of the Breast: Results of Combined Treatment with Surgery and Roentgen Therapy. PMID- 17858961 TI - Treatment of Cancer of the Breast in Premenopausal Patients with Radical Amputation and Bilateral Oophorectomy. PMID- 17858962 TI - The Surgical Treatment of Spontaneous Cerebrospinal Rhinorrhea. PMID- 17858963 TI - Tetra-ethyl-ammonium as an Adjunct in the Treatment of Peripheral Vascular Disease and Other Painful States. PMID- 17858964 TI - Wounds of the Liver. PMID- 17858965 TI - Wound Disruption and Early Ambulation. PMID- 17858966 TI - Wound Closure Without the Use of Grafts. PMID- 17858967 TI - Bilateral Cutaneous Ureterostomy Eighteen Years After Ureterosigmoidostomy for Exstrophy of the Bladder. PMID- 17858968 TI - Gastric Neurectomy for Gastric and Duodenal Ulceration : An Anatomic and Clinical Study. PMID- 17858969 TI - Shoulder and Elbow Lesions Distinctive of Baseball Players. PMID- 17858970 TI - Howard Merrill Clute: 1890-1946. PMID- 17858971 TI - Walter E. Dandy: 1886-1946. PMID- 17858972 TI - John Staige Davis: 1872-1946. PMID- 17858973 TI - Samuel Laban Ledbetter: 1886-1946. PMID- 17858974 TI - John Chadwick Oliver: May 7, 1862-March 14, 1946. PMID- 17858975 TI - Carcinoma of the Colon: Effect of Recent Advances on the Surgical Management. PMID- 17858976 TI - The Persistence of Symptoms Following Cholecystectomy. PMID- 17858977 TI - Bezoars Causing Acute Intestinal Obstruction. PMID- 17858978 TI - Surgical Care of Urinary Incontinence in Women. PMID- 17858979 TI - Gangrene (Noninfective) Complicating Fractures. PMID- 17858980 TI - The Management of Carcinoma in the Several Parts of the Colon. PMID- 17858981 TI - Carcinoma of the Thyroid. PMID- 17858982 TI - Primary Carcinoma of the Lung, with Invasion of the Ribs: Pneumonectomy and Simultaneous Block Resection of the Chest Wall. PMID- 17858983 TI - The Use of a Mixture of Pure Amino Acids in Surgical Nutrition : I. Certain Pharmacologic Considerations. PMID- 17858984 TI - The Clinical Behavior of Arteriosclerotic Aneurysm of the Abdominal Aorta: A Rational Surgical Therapy. PMID- 17858985 TI - Intravenous Oxygen and Pulmonary Embolism. PMID- 17858986 TI - Laryngo-esophagectomy. PMID- 17858987 TI - Leiomyoma of the Kidney. PMID- 17858988 TI - Congenital Absence of Gallbladder: Report of Three Cases. PMID- 17858989 TI - Management of Colostomies Performed for War Injuries. PMID- 17858990 TI - Multiple Polyposis of the Colon with Malignant Change Involving Colon and Appendix: Case Report. PMID- 17858991 TI - The Effects on Venous Endothelium of Alterations in Blood Flow Through the Vessels in Vein Walls, and the Possible Relation to Thrombosis. PMID- 17858992 TI - Duplications of the Alimentary Tract: Report of Six Cases. PMID- 17858993 TI - A Psychiatric Study of Sixty-one Appendicectomy Cases. PMID- 17858994 TI - Local Penicillin Therapy in Surgical Infections. PMID- 17858995 TI - A Successful Method for Securing Primary Wound Healing after Resection of Fistulae in Ano: A Preliminary Report. PMID- 17858996 TI - The Effect of Heparin upon Intra-abdominal Adhesions in Rabbits. PMID- 17858997 TI - The Question of Regeneration of Nerve Fibers to the Human Adrenal Gland after Bilateral Sympathectomy. PMID- 17858998 TI - Retroperitoneal Cysts. PMID- 17858999 TI - A Study of the Results of the Surgical Treatment of Varicose Veins. PMID- 17859000 TI - Persistent Omphalomesenteric (Vitelline) Artery Causing Intestinal Obstruction and Gangrene of Meckel's Diverticulum. PMID- 17859001 TI - How Long Should an Extremity be Immobilized after Nerve Suture? PMID- 17859002 TI - Address of the President: Science and Humanism in Surgery. PMID- 17859003 TI - Gastro-esophageal Resection and Total Gastrectomy in the Treatment of Bleeding Varicose Veins in Banti's Syndrome. PMID- 17859004 TI - Acute Cholecystitis Following the Surgical Treatment of Unrelated Disease. PMID- 17859005 TI - A Consideration of Pathological Factors Influencing Five Year Survival in Radical Resection of the Large Bowel and Rectum for Carcinoma. PMID- 17859006 TI - Adjuvants to Surgical Therapy in Large Bowel Malignancy. PMID- 17859007 TI - Observations on Mortality from Acute Appendicitis at a University Hospital, 1916 to 1946. PMID- 17859008 TI - Studies upon Spinal Cord Injuries : 1. The Development of Automatic Micturition. PMID- 17859009 TI - The Control of Cancer. PMID- 17859010 TI - The Specialty of Anesthesia : And its Application in the Harvard University Massachusetts General Hospital Department. PMID- 17859011 TI - Graduate Training in Surgery in Veterans Administration Hospitals. PMID- 17859012 TI - Toxoid Immunization in Experimental Gas Gangrene : A Preliminary Report. PMID- 17859013 TI - The Pathophysiology of the Cause of Death from Coronary Thrombosis. PMID- 17859014 TI - Factors Limiting Surgery for Essential Hypertension. PMID- 17859015 TI - The Paradox of Aciduria in the Presence of Alkalosis Caused by Hypochloremia. PMID- 17859016 TI - Essential Therapeutic Adjuvants in the Surgical Arrest of Wolff-Israel Actinomycosis. PMID- 17859017 TI - An Evaluation of Methods of Penicillin Therapy in Thoracic Surgery. PMID- 17859018 TI - Studies in Postoperative Convalescence. PMID- 17859019 TI - Repair of Sliding Inguinal Hernia Through the Abdominal (Laroque) Approach. PMID- 17859020 TI - Repair of Major Facial Injuries. PMID- 17859021 TI - Subtotal Gastrectomy for Gastric Ulcer. PMID- 17859022 TI - The Effect of Vagotomy on Human Gastric Function: A Preliminary Report. PMID- 17859023 TI - Vagus Resection for Ulcer: An Interim Evaluation : II. Clinical Results. PMID- 17859024 TI - A Study of the Results, both Favorable and Unfavorable, of Section of the Vagus Nerves in the Treatment of Peptic Ulcer. PMID- 17859025 TI - Section of the Vagus Nerves to the Stomach in the Treatment of Peptic Ulcer : Complications and End Results After Four Years. PMID- 17859026 TI - Abdominal Visceral Sensation in Man. PMID- 17859027 TI - The Role of Pinealomas in the Causation of Diabetes Insipidus. PMID- 17859028 TI - The Treatment of Focal Epilepsy by Cortical Excision. PMID- 17859029 TI - Urgent Surgery in the Aged. PMID- 17859030 TI - Experiences in the Surgical Treatment of Multiple Visceral Neoplasms. PMID- 17859031 TI - Resection and Primary Anastomosis in the Treatment of Gangrenous or Non-reducible Intussusceptions in Children : A Safe, Simple, One-Layer Silk Anastomosis. PMID- 17859032 TI - Mediastinal Aberrant Goiter. PMID- 17859033 TI - Inflammatory Obliteration of the Common and Hepatic Ducts Following Cholecystectomy. PMID- 17859034 TI - The Appendiceal Stump. PMID- 17859035 TI - Talcum Powder Granuloma: A Frequent and Serious Postoperative Complication. PMID- 17859036 TI - A Suspension Operation for Prolapse of the Rectum. PMID- 17859037 TI - Letter to the Editor. PMID- 17859038 TI - On the Specific Role of the Liver in Hemorrhagic Shock: Report of Progress to Date. PMID- 17859039 TI - The Redistribution of Body Water and the Fluid Therapy of the Burned Patient. PMID- 17859040 TI - Restorative Endoaneurysmorrhaphy by Vein Graft Inlay. PMID- 17859041 TI - The "Borrowing-lending" Hemodynamic Phenomenon (Hemometakinesia) and its Therapeutic Application in Peripheral Vascular Disturbances. PMID- 17859042 TI - Arterial Injuries. PMID- 17859043 TI - Sympathectomy for Obliterative Arterial Disease; Indications and Contraindications. PMID- 17859045 TI - Experiences with a Bone Bank. PMID- 17859044 TI - Chondrosarcoma. PMID- 17859046 TI - Penetrating Wounds of Major Joints. PMID- 17859047 TI - Pulmonary Cavernous Hemangioma with Arteriovenous Fistula, Surgical Management. PMID- 17859048 TI - Control of Hemorrhage from Wounds of the Heart by the Gelatin Sponge "Patch" Technic : A New Experimental Method. PMID- 17859049 TI - Familial Hemolytic Anemia and its Surgical Aspect with Special Reference to a Case Complicated by the Rh Factor. PMID- 17859050 TI - Ligation and Division of the Abdominal Aorta for Metallic Embolus from the Heart: Postoperative Observations of the Circulation in the Extremities. PMID- 17859051 TI - Ischemic Necrosis of the Anterior Crural Muscles. PMID- 17859052 TI - One-Stage Resection and Anastomosis of the Colon: Utilizing the Furniss Clamp. PMID- 17859053 TI - Obstructive Lesions of the Small Intestine and Sigmoid Due to Irradiation. PMID- 17859054 TI - The Anatomy of the Peri-Esophageal Vagi. PMID- 17859055 TI - Prolonged Intercostal Nerve Block in Upper Abdominal Operations. PMID- 17859056 TI - A Technic for Blocking the Carotid Sinus Nerves. PMID- 17859057 TI - Pancreatic Calculi. PMID- 17859058 TI - Cystadenoma of the Pancreas. PMID- 17859059 TI - Mucocele of the Appendix, with Myxoglobulosis. PMID- 17859060 TI - Carcinoma of the Breast in the Absence of Clinical Breast Findings. PMID- 17859061 TI - Hamartoma of the Liver. PMID- 17859062 TI - A Case of Glomus Tumor with Primary Involvement of Bone. PMID- 17859063 TI - The Arterial Supply of the Distal Colon Pertinent to Abdominoperineal Proctosigmoidectomy, with Preservation of the Sphincter Mechanism. PMID- 17859064 TI - Surgical Treatment of Cardiospasm. PMID- 17859065 TI - Spontaneous Rupture of the Malarial Spleen: Case Report and Analysis of 64 Reported Cases. PMID- 17859066 TI - Penetrating Wounds of the Cerebral Ventricles. PMID- 17859067 TI - Some Effects of Experimental Thermal Burns on Vascular Endothelium Employing a Perfusion Technic in Anesthetized Dogs. PMID- 17859068 TI - Homogenous Fetal Cartilage Grafts to Bone: An Experimental Study. PMID- 17859069 TI - Acromioclavicular Dislocation: End-Results of Screw Suspension Treatment. PMID- 17859070 TI - The Syndrome of Thrombotic Obliteration of the Aortic Bifurcation. PMID- 17859071 TI - The Problem of Maintaining the Continuity of the Artery in the Surgery of Aneurysms and Arteriovenous Fistulae: Notes on the Development and Clinical Application of Methods of Arterial Suture. PMID- 17859072 TI - Conservative Surgery in Tumors of Bone with Special Reference to Segmental Resection. PMID- 17859073 TI - The Closure of Colostomies. PMID- 17859074 TI - Modern Concepts of Ureteral Calculi. PMID- 17859075 TI - Carotid Body Tumors. PMID- 17859076 TI - Mesenchymoma, the Mixed Tumor of Mesenchymal Derivatives. PMID- 17859077 TI - Lingual Goiter: Report of Three Cases. PMID- 17859078 TI - Concerning Surgical Treatment of Traumatic Injury to the Upper Division of the Brachial Plexus (Erb's Type). PMID- 17859079 TI - Observations upon Patients with Penetrating Wounds Involving the Cerebellum. PMID- 17859080 TI - The Subarachnoid Use of Vasoconstrictors in Spinal Anesthesia. PMID- 17859081 TI - A Method of Partitioning Liver Proteins and its Application to the Study of the Effects of Acute Hemorrhage in the Dog. PMID- 17859082 TI - Blood and Liver Proteins in Surgical Patients as Related to Protein Depletion. PMID- 17859083 TI - A Simplification of the Diagnosis of Varicose Veins. PMID- 17859084 TI - Giant Intracanalicular Fibro-adenoma of the Breast: Report of a Case. PMID- 17859085 TI - Massive Resection of the Small Intestine. PMID- 17859086 TI - Complete Transposition of the Aorta and the Pulmonary Artery: Experimental Observations on Venous Shunts as Corrective Procedures. PMID- 17859087 TI - The Sigmoid as a Source of Right-Sided Symptoms. PMID- 17859089 TI - Gastroduodenal Ulcer, A Splastic Disease. PMID- 17859088 TI - New Donor Areas in Skin Grafting. PMID- 17859090 TI - Rationale of Parenteral Glucose Feeding in the Postoperative State. PMID- 17859091 TI - Disasters following the Operation of Ligation and Retrograde Injection of Varicose Veins. PMID- 17859092 TI - Sacrococcygeal Chordoma. PMID- 17859093 TI - Plasma Silk Suture of Nerves. PMID- 17859094 TI - Operative Exposure of the Blood Vessels in the Superior Anterior Mediastinum. PMID- 17859095 TI - Bronchiogenic Cysts of the Mediastinum. PMID- 17859096 TI - Mid-leg Amputations for Gangrene in the Diabetic. PMID- 17859097 TI - Juvenile Nasopharyngeal Angiofibroma. PMID- 17859099 TI - A Simultaneous Abdominal and Perineal Approach in Operations for Imperforate Anus with Atresia of the Rectum and Rectosigsmoid. PMID- 17859098 TI - Transperitoneal Approach to the Intervertebral Disc in the Lumbar Area. PMID- 17859100 TI - Acute Pancreatitis. PMID- 17859101 TI - Bursitis under Fibular Collateral Ligament. PMID- 17859102 TI - Traumatic Aneurysm of the Subscapular Artery. PMID- 17859103 TI - Cysts of the Spleen: Case Report. PMID- 17859104 TI - Marrow-mailing of Recent Fractures, Pseudarthrosis and Bone Plastic: Experiences in 100 Cases. PMID- 17859105 TI - Cardiac Resuscitation. PMID- 17859106 TI - Metabolic Study of Burn Cases. PMID- 17859108 TI - Thyroiditis. PMID- 17859107 TI - The Surgical Triangles of the Inguinopectineal Region (Inguina): Their Classification, Parietal Relationship and Significance in Hernia Repair. PMID- 17859109 TI - Coarctation and Aneurysm of the Aorta: Report of a Case Treated by Excision and End-to-End Suture of Aorta. PMID- 17859110 TI - The Changing Scene in American Surgery. PMID- 17859112 TI - The Selection of Patients for Thoracolumbar Sympathectomy: Description of a Set of Rules for the Elimination of Failures and Fatalities. PMID- 17859111 TI - Uterine Anomaly: Duplication of Uterus, Three Tubes and Three Ovaries: Report of a Case. PMID- 17859113 TI - Constrictive Pericarditis with Tuberculous Intrapericardial Abscess Treated by Streptomycin: Report of a Case. PMID- 17859114 TI - "Functional" Subclavian Arterial Murmur: Possible Relation to Scalenus Anticus Syndrome, Costoclavicular Compression, or the Neurovascular Syndrome of Wright. PMID- 17859116 TI - Myoxma, the Tumor of Primitive Mesenchyme. PMID- 17859115 TI - Peripheral Nerve Surgery: Repair of Nerve Defects. PMID- 17859117 TI - Raynaud's Phenomenon and Atypical Causalgia; the Role of Sympathectomy. PMID- 17859118 TI - Multiple Intussusceptions, Direct and Retrograde, of Traumatic Origin. PMID- 17859120 TI - Congenital Absence of the Gallbladder. PMID- 17859119 TI - Carcinosarcoma of the Uterus. PMID- 17859121 TI - Hydrocele of the Canal of Nuck with Large Cystic Retroperitoneal Extension. PMID- 17859122 TI - Lipoma of the Duodenum Causing Melena. PMID- 17859123 TI - A New Method of Restoring Continuity of the Alimentary Canal in Cases of Congenital Atresia of the Esophagus with Tracheo-esophageal Fistula not Treated by Immediate Primary Anastomosis. PMID- 17859125 TI - Rationale and Results in Retropubic Prostatectomy. PMID- 17859124 TI - LETTER TO THE EDITOR. PMID- 17859126 TI - Current Trends in Surgery of the Distal Colon and Rectum for Cancer. PMID- 17859127 TI - Familial Polyposis and Carcinoma of the Colon. PMID- 17859128 TI - Low Anterior Segmental Resection with or without Colostomy. PMID- 17859129 TI - The Surgical Treatment of Peptic Ulcer : A Comparison of the Results of Castro enterostomy, Gastric Resection and Vagotomy at the Duke Hospital. PMID- 17859130 TI - The Surgical Treatment of Obstructive Lesions of the Esophagus. PMID- 17859131 TI - Preliminary Report on the Use of Tantalum Mesh in the Repair of Ventral Hernias. PMID- 17859132 TI - Perineal Hernia: Report of a Case Occurring in a Male. PMID- 17859133 TI - The Management of Penetrating Abdominal Injuries : Comparative Military and Civilian Experiences. PMID- 17859134 TI - Aneurysm following Surgical Procedures : Report of Five Cases. PMID- 17859135 TI - Aneurysm of the Left Common Iliac Artery Secondary to a Traumatic Arteriovenous Fistula of the Left Popliteal Vessels. PMID- 17859136 TI - Endometriosis. PMID- 17859137 TI - The Clinical Evaluation of Cholangiograms. PMID- 17859138 TI - Acute Cholecystitis. PMID- 17859139 TI - A Clinical Evaluation of Cherney's Incision. PMID- 17859140 TI - "Wet Lung"-An Experimental Study : I. The Effects of Trauma and Hypoxia. PMID- 17859141 TI - Facial Paralysis Supported with Autogenous Fascia Lata. PMID- 17859142 TI - Preservation and Restoration of Mandibular Function and Contour. PMID- 17859143 TI - Prolapse of the Gastric Mucosa: Report of Six Cases. PMID- 17859144 TI - Mesenteric Vascular Occlusion. PMID- 17859145 TI - Lymphangioma of the Mesentery. PMID- 17859146 TI - Enterogenous Cysts of the Duodenum. PMID- 17859147 TI - Jejunal Diverticulosis Complicated by the Development of Jejuno-Colic and Jejunal Fistulas: Report of a Case. PMID- 17859148 TI - Diploic Epidermoid and Extra-Dural Pneumatocle: Cranial Defects and Deformity. PMID- 17859150 TI - The Effects of Priscol (2 Benzyl-4, 5 Imidazoline HCl) on Peripheral Vascular Diseases, Hypertension and Circulation in Patients. PMID- 17859149 TI - Anatomical Observations on the Lumbar Sympathetics with Evaluation of Sympathectomies in Organic Peripheral Vascular Disease. PMID- 17859151 TI - Carcinoma of the Breast. PMID- 17859152 TI - The Definition of Inoperability of Cancer. PMID- 17859153 TI - The Surgical Treatment of the Infantile Type of Coarctation of the Aorta. PMID- 17859154 TI - Battle Wounds and Injuries of the Heart and Pericardium: Experiences in Forward Hospitals. PMID- 17859155 TI - Fractures of the Acetabulum: The Nature of the Traumatic Lesions, Treatment, And Two-Year End-Results. PMID- 17859156 TI - Experimental Studies of Alginates as Hemostatics. PMID- 17859158 TI - Significant Anatomic Relations in the Syndrome of the Scalene Muscles. PMID- 17859157 TI - The Toxicity of Sodium Alginate in Cats. PMID- 17859159 TI - The Local Injection of Penicillin in Acute Circumscribed Infections. PMID- 17859160 TI - Temporary Failure of Gallbladder Visualization by Cholecystography in Acute Pancreatitis. PMID- 17859161 TI - A Dependable Method for Constant Intravenous Therapy in Infants Using Polyethylene Tubing. PMID- 17859162 TI - Phlebography in the Localization of Incompetent Communicating Veins in Patients with Varicose Veins. PMID- 17859163 TI - Perforation of Ileum by Ingested Chicken Bone Complicating Ventral Hernia. PMID- 17859164 TI - The Accidental Operative Transplantation of Benign Giant Cell Tumor. PMID- 17859165 TI - Primary Carcinoma of the Liver: Report of a Case Treated by Lobectomy. PMID- 17859166 TI - Pseudoembolic Phlebitis with Ligation of the Inferior Vena Cava: A Case Report. PMID- 17859167 TI - Choledocho-duodeno-jejunal Intubation for Feeding Following Choledochostomy. PMID- 17859168 TI - Carcinoma of the Premenopausal Breast: Endocrine Influence Suggested Clinically in 31 Cases. PMID- 17859169 TI - Letters to the Editor. PMID- 17859170 TI - Letters to the Editor. PMID- 17859172 TI - On the Use of N. Musculocutaneous for Neurotization of N. Radialis in Cases of Very Large Defects of the Latter. PMID- 17859171 TI - Temporary Interruption of the Sympathetic Impulses to the Head by Infiltration of the Cervical Sympathetic Trunk. PMID- 17859173 TI - The Use of Mechanically Wound Bobbins for Handling and Dispensing Non-absorbable Suture Material, with Observations on the Tensile Strength and Sterility of Mechanically Wound Suture Material. PMID- 17859174 TI - Carcinoid Tumors of the Rectum-Report of Three Cases, Two with Metastases. PMID- 17859175 TI - Morbidity and Mortality in Talc Granuloma: Report of a Fatal Case. PMID- 17859176 TI - The Problem of Peptic Ulcer Following Pancreatectomy. PMID- 17859177 TI - An Unusual Complication of a Meckelian Diverticulum. PMID- 17859178 TI - Chylous Mesenteric Cyst : Case Report. PMID- 17859179 TI - Experimental Repair of Common Duct Defects Utilizing a Free Vein Graft Over Blakemore-Lord Tubes. PMID- 17859180 TI - Result Following Subtotal Gastrectomy for Duodenal and Gastric Ulcer. PMID- 17859181 TI - Conservative Therapy of Residual Calculi Following Operations on the Common Bile Duct : Report of Two Cases. PMID- 17859182 TI - Blood Fat Levels Following Supradiaphragmatic Ligation of the Thoracic Duct. PMID- 17859183 TI - Streptomycin in Surgical Infections-Part IV. Infections of Soft Tissues. PMID- 17859184 TI - Penicillin in the Postoperative Treatment of Peptic Ulcer with Perforation and Appendicitis with Perforation. PMID- 17859185 TI - Resurfacing Procedures in Compound Injuries of Lower Extremities. PMID- 17859186 TI - Urologic Complications of Left Colon Surgery. PMID- 17859187 TI - Sacrococcygeal Teratomata in Infancy-A Report of Six Cases. PMID- 17859189 TI - Effect of Vagotomy and of Drugs on Gastric Motility. PMID- 17859188 TI - Causalgia Following Gunshot Injuries of Nerves : Role of Emotional Stimuli and Surgical Cure through Interruption of Diencephalic Efferent Discharge by Sympathectomy. PMID- 17859190 TI - Pure Serum Albumin Compared with Citrated Plasma in the Therapy of Chronic Hypoalbuminemia. PMID- 17859191 TI - Strangulated Diaphragmatic Hernia. PMID- 17859192 TI - Reconstruction of the External Ear. PMID- 17859193 TI - Choledochus Cyst: Case Report with Brief Comment. PMID- 17859194 TI - Internal Hernia with Strangulation of Bowel Due to a Defect in the Falciform Ligament. PMID- 17859195 TI - Acute Torsion of the Gallbladder. PMID- 17859196 TI - Saddle Embolus of the Aorta: Report of Successful Embolectomy. PMID- 17859197 TI - The Histochemistry of Burned Human Skin: With a Note on Base Exchange in Traumatized Tissue. PMID- 17859198 TI - Polypoid Adenomatosis of the Entire Gastrointestinal Tract. PMID- 17859199 TI - Tumor of the Small Intestine : Miller-Abbott Tube Determines Site of Massive Hemorrhage. PMID- 17859200 TI - Recurrent Primary Thrombocytopenic Purpura with Accessory Spleens: Review of the Literature. PMID- 17859201 TI - Streptomycin in Surgical Infections.-Part VI. Lung Abscess and Empyema. PMID- 17859202 TI - Memoir: Enrique Finochietto, M.D. (1881-1948). PMID- 17859203 TI - Address of the President: He Shall Have a Noble Memory. PMID- 17859204 TI - Strictures of the Common Duct. PMID- 17859205 TI - The Quantitative and Qualitative Control of Bile Flow and Its Relation to Biliary Tract Surgery. PMID- 17859206 TI - Splenectomy: When Is It Indicated? PMID- 17859207 TI - The Treatment of Renal Insufficiency in the Surgical Patient. PMID- 17859209 TI - Stress, Strain and Sutures. PMID- 17859208 TI - The Significance of Urine Chloride Determination in the Detection and Treatment of Dehydration with Salt Depletion. PMID- 17859210 TI - Further Studies on the Cytologic Method in the Problem of Gastric Cancer. PMID- 17859211 TI - Anterior Resection for Malignant Lesions of the Upper Part of the Rectum and Lower Part of the Sigmoid. PMID- 17859212 TI - The Significance of the Protein-bound Blood Iodine in Patients with Hyperthyroidism. PMID- 17859213 TI - Dorsal Cordotomy for Painful Phantom Limb. PMID- 17859214 TI - A Comparative Study of Subtotal Gastrectomy with and without Vagotomy. PMID- 17859215 TI - The Response to Vagotomy in Idiopathic Ulcerative Colitis and Regional Enteritis. PMID- 17859217 TI - Studies on the Use of Polythene as a Fibrous Tissue Stimulant. PMID- 17859216 TI - Pharmacologic Factors Influencing Collateral Respiration: Possible Relation to the Etiology of Pulmonary Complications. PMID- 17859218 TI - Prothrombin Activity : A Diagnostic Test for Early Postoperative Venous Thrombosis. PMID- 17859219 TI - Endothelioma of Bone. PMID- 17859220 TI - Further Experiences with Peritoneal Irrigation for Acute Renal Failure: Including a Description of Modifications in Method. PMID- 17859221 TI - Recurrent Acute Pancreatitis: Observations on Etiology and Surgical Treatment. PMID- 17859222 TI - Observations on Some Metabolic Changes after Pancreatoduodenectomy. PMID- 17859223 TI - Colorimetric Determination of Amylase. PMID- 17859224 TI - Surgical Experiences with Extramedullary Tumors of the Spinal Cord. PMID- 17859225 TI - The Control of Anoxemia during Surgical Anesthesia with the Aid of the Oxyhemograph. PMID- 17859226 TI - Penicillin Therapy with Prolonged Interval Dosage Schedules. PMID- 17859227 TI - The Results of the Systemic Administration of the Antibiotic, Bacitracin, in Surgical Infections: A Preliminary Report. PMID- 17859228 TI - Paralysis of Deglutition: Surgical Correction. PMID- 17859229 TI - Late Complications Following Cranioplasty with Alloplastic Plates. PMID- 17859230 TI - The Clinical Aspects of Chronic Thyroiditis. PMID- 17859232 TI - Gangliosympathectomy and Bilateral Hemiadrenalectomy for Severest Grade of Hypertension. PMID- 17859231 TI - The Results of a Specifically Co-ordinated Plan of Medical and Surgical Treatment of Essential Hypertension. PMID- 17859233 TI - Management of Massively Bleeding Peptic Ulcer. PMID- 17859235 TI - The Portacaval Shunt in the Surgical Treatment of Portal Hypertension. PMID- 17859234 TI - The Surgical Treatment and the Physiopathology of Coarctation of the Aorta. PMID- 17859236 TI - Closure of Defects in Cardiac Septa. PMID- 17859237 TI - Revascularization of the Heart. PMID- 17859238 TI - The Factor of Rate of Transfusion with Particular Reference to the Intra-arterial Route. PMID- 17859239 TI - Severe Crushing Injury to the Chest: Report of a Case having Extensive Bilateral Rib Fractures Successfully Treated by Pericostal Skeletal Traction. PMID- 17859240 TI - Herniation of the Heart : Through a Pericardial Incision. PMID- 17859241 TI - Mycetoma-Madura Foot: A Case of Mycetoma Pedis in Chicago. PMID- 17859242 TI - Volvulus of the Sigmoid Colon: Report of Two Cases. PMID- 17859243 TI - Gastroduodenal Intussusception : A Case Report. PMID- 17859244 TI - Cholecystitis due to Giardia Lamblia in a Left-sided Gallbladder. PMID- 17859245 TI - Mediastinal Lipomata: A Case Report. PMID- 17859246 TI - Observations on Visceral Pain : (1) Visceral Tenderness. PMID- 17859247 TI - Hemophilia: Problem of Surgical Intervention for Accompanying Diseases. Review of the Literature and Report of a Case. PMID- 17859248 TI - Reduction of Intussusception by Barium Enema : A Clinical and Experimental Study. PMID- 17859249 TI - Primary "Inflammatory" Carcinoma of the Breast : A Report of Five Cases and a Review of the Literature. PMID- 17859250 TI - The Silent Gallstone: A Ten to Twenty Year Follow-up Study of 112 Cases. PMID- 17859251 TI - Thoraco-abdominal Approach for Portacaval Anastomosis: With a Case Report of Portacaval Shunt Employing this Method. PMID- 17859252 TI - The Right Thoraco-abdominal Approach. PMID- 17859253 TI - Experience with Three Thousand Cases of Brachial Plexus Block: Its Dangers: Report of a Fatal Case. PMID- 17859254 TI - Femoral Hernia: A Technic of Repair : The Clinic. PMID- 17859255 TI - Results of Treatment of Perforation of the Esophagus. PMID- 17859256 TI - Treatment of Pancreatic Cysts. PMID- 17859257 TI - Pancreatic Pseudocysts: Report of a Case Treated by Cystogastrostomy. PMID- 17859258 TI - Oral Streptomycin in Surgery of the Large Bowel: The Production of Secondary Hypoprothrombinemia. PMID- 17859259 TI - Control of the Common Iliac Artery during Sacroiliac Disarticulation (Hemipelvectomy). PMID- 17859260 TI - Adamantinoma of the Maxilla Metastatic to the Lung: Case Report. PMID- 17859261 TI - The Nature of the Shift of Plasma Protein to the Extravascular Space Following Thermal Trauma. PMID- 17859262 TI - Traumatic Chylothorax : A Review of the Literature and Report of a Case Treated by Ligation of the Thoracic Duct and Cisterna Chyli. PMID- 17859263 TI - Rectal Stricture of Lymphogranuloma Venereum. PMID- 17859264 TI - Tetraethyl Ammonium Chloride-Its Effects on Surface Temperatures of Extremities in Peripheral Vascular Conditions. PMID- 17859265 TI - Tetraethyl Ammonium Chloride-Its Effects on Surface Temperatures of Atherosclerotic Extremities. PMID- 17859266 TI - Chronic Progressive Infectious Gangrene of the Skin : A Patient with Exposure to Cold Wave Solution. PMID- 17859267 TI - A Study of the Beta 17 Ketosteroids in a Case of Pseudo-hermaphroditism Due to Adrenal Cortical Tumor. PMID- 17859268 TI - Evaluation of the Open Jump Flap for Lower Extremity Soft Tissue Repair. PMID- 17859269 TI - Carcinoma Developing in Sebaceous Cysts. PMID- 17859270 TI - Comparison of the Efficacy of Therapeutic Agents in the Treatment of Experimentally Induced Diffuse Peritonitis of Intestinal Origin. PMID- 17859271 TI - Giant Cell Tumor of the Sacrum: A Case Report. PMID- 17859272 TI - Choledochus Cyst Associated with Congenital Atresia of the Bile Ducts. PMID- 17859273 TI - Traumatic Rupture of the Choledochus, Associated with an Acute Hemorrhagic Pancreatitis and a Bile Peritonitis. PMID- 17859274 TI - Multiple Carcinomas of the Stomach. PMID- 17859275 TI - Internal Hernia Behind the Jejunal Loop of a Posterior Gastro-enterostomy. PMID- 17859276 TI - Response to Parenteral Glucose of Normal Kidneys and of Kidneys of Postoperative Patients. PMID- 17859277 TI - Surgical Repair of Lacerations and Fistulas of the Parotid Duct. PMID- 17859278 TI - Acute Diverticulitis of the Cecum : Report of Three Cases Diagnosed Pre Operatively as Acute Appendicitis. PMID- 17859279 TI - The Use of Full Thickness Skin Grafts in the Repair of Large Herniae. PMID- 17859280 TI - Cirsoid Aneurysm of the Scalp: Report of a Case. PMID- 17859281 TI - Primary Splenic Neutropenia: A Specific Indication for Splenectomy : Report of a Case. PMID- 17859282 TI - Unusual Metastatic Manifestations of Breast Carcinoma: III. Metastatic involvement of Preauricular Lymph Nodes and Parotid Gland. A Report of Five Cases. PMID- 17859283 TI - Appraisal of Oral Streptomycin as an Intestinal Antiseptic, with Observations on Rapid Development of Resistance of E. Coli to Streptomycin. PMID- 17859284 TI - Bridging of Esophageal Defect by Pedicled Flap of Lung Tissue. PMID- 17859285 TI - Rupture of a Subphrenic Abscess into the Pericardium. PMID- 17859286 TI - Intraparotid Sebaceous Glands. PMID- 17859287 TI - Certain Anatomic Factors Related to the Pathogenesis of Hemorrhoids : The Author's "Obliterative Suture" in the Treatment of the Small and Middle-Sized Internal Hemorrhoids. PMID- 17859289 TI - Malignant Tumors of the Colon and Rectum. PMID- 17859288 TI - The Importance of the Level of the Lesion in the Prognosis and Treatment of Carcinoma of the Rectum and Low Sigmoid Colon. PMID- 17859290 TI - The Management of Massive Gastroduodenal Hemorrhage. PMID- 17859291 TI - An Experimental Study of Antiperistaltic Jejunal Loops. PMID- 17859292 TI - Sympathectomy in Peripheral Arteriosclerosis. PMID- 17859293 TI - Tissue Reaction to Plastics Used in Surgery with Special Reference to Teflon. PMID- 17859294 TI - Experimental Pulmonary Collapse. PMID- 17859295 TI - Streptomycin in Surgical Infections. Part VII-Non-pulmonary Tuberculosis (Lymph Nodes, Urinary Tract, Bone, and Peritoneum). PMID- 17859296 TI - Experimental Reconstruction of Cardiac Valves by Venous and Pericardial Grafts. PMID- 17859297 TI - The Metabolism of Calcium in Patients with Spinal Cord Injuries. PMID- 17859298 TI - Displacement of the Esophagus into a New Diaphragmatic Orifice in the Repair of Paraesophageal and Esophageal Hiatus Hernia. PMID- 17859299 TI - Sigmoidocutaneous Fistulae Resulting from Diverticulitis of the Sigmoid Colon. PMID- 17859300 TI - A Neurogenic Factor in Experimental Traumatic Shock: A Summary of Recent Studies Including Observations on Procainized and Spinal Dogs. PMID- 17859301 TI - A Discussion of Tendon Repair: With Clinical and Experimental Data on the Use of Gelatin Sponge. PMID- 17859302 TI - A Technic of Exposure for Diverticula of the Third and Fourth Parts of the Duodenum. PMID- 17859303 TI - The Surgical Treatment of Hernia in the Aged: A Study of Eighty-two Consecutive Patients over Sixty years of age. PMID- 17859304 TI - Surgery in Situs Inversus. PMID- 17859305 TI - Factors in the Mortality of the Ruptured Appendix. PMID- 17859306 TI - Neurofibroma: Benign Intraspinal-Intrathoracic "Hour-Glass" Tumor with Paraplegia. PMID- 17859307 TI - Gumma of the Lung: Report of a Case treated by Lobectomy. PMID- 17859308 TI - Congenital Microcolon: A Case Report. PMID- 17859309 TI - Massive Hematemesis : Analysis of 300 consecutive cases. PMID- 17859310 TI - The Management of Bleeding Duodenal Ulcers. PMID- 17859311 TI - The Effect of Injury on Wound Healing. PMID- 17859312 TI - The Surgical Management of Chronic Recurrent Intestinal Obstruction Due to Adhesions. PMID- 17859313 TI - Wedge Osteotomy for Fresh Intracapsular Fractures of the Neck of the Femur. PMID- 17859314 TI - Tissue-culture Evaluation of the Viability of Blood Vessels Stored by Refrigeration. PMID- 17859315 TI - The Medical and Surgical Treatment of Hypertension. PMID- 17859316 TI - Control of Hemorrhage from Wounds of the Coronary Vessels by the Gelatin Sponge Patch Technic: An Experimental Study. PMID- 17859317 TI - Total Gastrectomy for Carcinoma of the Stomach. PMID- 17859318 TI - Chemosurgical Treatment of Tumors of the Parotid Gland : A Microscopically Controlled Method of Excision. PMID- 17859319 TI - Resection of the Sternum for Metastatic Carcinoma. PMID- 17859320 TI - Hypernephroma Metastatic to the Thyroid Gland: Report of a Case. PMID- 17859321 TI - Retrograde Intragastric Intussusception of the Jejunum Following Subtotal Gastrectomy: Report of a Case, Apparently the Second such in the Literature. PMID- 17859322 TI - Wandering Spleen: Report of a Case Complicated by a Traumatic Cyst. PMID- 17859323 TI - A Preliminary Report on the Advantages of a Small Stoma in Partial Gastrectomy for Ulcer. PMID- 17859324 TI - The Operative Treatment of Pectus Excavatum. PMID- 17859325 TI - The Treatment of Acute Anuria : With Evaluation of Peritoneal Lavage. PMID- 17859327 TI - Prophylaxis of Ovarian Cancer. PMID- 17859326 TI - Glucose Assimilation during Anesthesia and Surgery. PMID- 17859328 TI - Rationale of Therapy in Acute Vascular Occlusions Based upon Micrometric Observations. PMID- 17859329 TI - The Treatment of Carbuncles by the Local Injection of Penicillin. PMID- 17859331 TI - Adamantinoma of the Mandible : A Case Report. PMID- 17859330 TI - Complete Excision of Pelvic Viscera in the Male for Advanced Carcinoma of the Sigmoid Invading the Urinary Bladder. PMID- 17859332 TI - Spontaneous Rupture of the Esophagus. PMID- 17859333 TI - Congenital Intestinal Atresia. PMID- 17859335 TI - Anomalous Insertion of the Right Hepatic Duct into the Cystic Duct : Report of a Case and Review of the Literature. PMID- 17859334 TI - Multiple Lipomas of the Stomach and Duodenum. PMID- 17859336 TI - Primary Inflammation of the Appendices Epiploicae : With Review of the Literature and Report of Six Additional Cases. PMID- 17859337 TI - Angiosarcoma of the Colon : With Case Report. PMID- 17859338 TI - Letter to the Editor. PMID- 17859339 TI - Presidential Address: The Surgical Man. PMID- 17859340 TI - Sex Ratio: Experimental Studies Demonstrating Controlled Variations - Preliminary Report. PMID- 17859341 TI - The Treatment of Congenital Atresia of the Esophagus with Tracheo-esophageal Fistula. PMID- 17859342 TI - Esophageal Resection with End-to-end Anastomosis: Experimental and Clinical Observations. PMID- 17859343 TI - The Surgical Treatment of Pulsion Diverticula of the Thoracic Esophagus. PMID- 17859344 TI - Esophageal Rupture Complicating Craniotomy-Symptom Complex and Proposed Surgical Treatment. PMID- 17859345 TI - Treatment of Hyperthyroidism in Children. PMID- 17859346 TI - Thyroglossal Cysts and Sinuses. PMID- 17859347 TI - Primary Repair of Severed Parotid Duct: Review of Literature and Report of Three Cases. PMID- 17859348 TI - Distention of the Subarachnoid Space with Cerebrospinal Fluid in Infants: Enlargement of the Head and Spasticity-Surgical Correction. PMID- 17859349 TI - Hyperfunctioning Tumors of the Adrenal Cortex with Report of Eight Cases. PMID- 17859351 TI - Chondroblastic Tumors of Bone: Benign and Malignant. PMID- 17859350 TI - Indications and Results of Splenectomy. PMID- 17859352 TI - Calcium Deposits in the Vicinity of the Shoulder and of Other Joints. PMID- 17859353 TI - Partial Hepatectomy with Intrahepatic Cholangiojejunostomy : A Useful Addition to Technical Methods for the Management of Common Duct Stricture. PMID- 17859354 TI - Combined Supraduodenal and Transduodenal Exploration of the Common Bile Duct. PMID- 17859355 TI - Application of Technics of Reconstructive Surgery to Certain Problems in General Surgery. PMID- 17859356 TI - Thrombosis and Embolism : The Five-Year Experience of a Small General Hospital. PMID- 17859357 TI - Comparison of Effectiveness of Newer Antibiotics in Experimental Peritonitis: A Preliminary Report. PMID- 17859358 TI - The Effects of Intramuscular and Intrathecal Administration of Streptomycin in Normal Dogs and in Dogs with Meningitis due to Escherichia Coli. PMID- 17859359 TI - Ultraviolet Radiation as an Adjunct in the Control of Postoperative Neurosurgical Infection: II Clinical Experience 1938-1948. PMID- 17859360 TI - Reduplication of the Stomach : Report of a Case. PMID- 17859362 TI - An Appraisal of Pancreatoduodenal Resection: A Follow-up Study of 61 Cases. PMID- 17859361 TI - The Management of Patients with Bleeding from the Upper Gastro-intestinal Tract with Buffer and Thrombin Solution. PMID- 17859364 TI - An Evaluation of the Treatment of Essential Hypertension by Sympathectomy. PMID- 17859363 TI - Results of Treatment of Patients with Hypertension by Total Thoracic and Partial to Total Lumbar Sympathectomy, Splanchnicectomy and Celiac Ganglionectomy. PMID- 17859365 TI - Presacral Enterogenous Cyst. PMID- 17859366 TI - I. Surgical Treatment of Tumors of the Bladdder. PMID- 17859367 TI - II. On Lumbar Hernia. PMID- 17859368 TI - III. New Methods for Compressing the Subclavian Artery, and for Ascertaining whether the Bladder is or is not Ruptured. PMID- 17859369 TI - IV. Further Report of Results obtained in a case of Removal of the Posterior Wall of the Spinal Canal and Opening of the Dura Mater Spinalis in the upper Dorsal Region for Paraplegia. PMID- 17859371 TI - II. Steinhaus on the Etiology of Acute Suppuration. PMID- 17859370 TI - I. Reichel on Etiology and Treatment of Acute Peritonitis. PMID- 17859372 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859373 TI - II. Rupture of the Middle Meningeal Artery, without Fracture; Ligation of Common Carotid Artery for Secondary Haemorrhage. PMID- 17859374 TI - III. Removal of an Eight Ounce Vesical Calculus by the Suprapubic Route. PMID- 17859376 TI - V. A Case of Fracture or the Styloid Processes of the Ulna and the Radius by Indirect Violence. PMID- 17859375 TI - IV. Rupture of the Rectum by Petersen's Calpeurynter during an Attempt to perform Intra-Peritoneal Cystotomy. PMID- 17859377 TI - VI. Note on the Use of Skin from Puppies in Skin-Grafting. PMID- 17859378 TI - I. Operations for the Radical Cure of Hernia in Hamburg. PMID- 17859379 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859380 TI - I. Nephrorrhaphy. PMID- 17859381 TI - I. The Operative Treatment of Goitre. PMID- 17859382 TI - I. Recent Scandinavian Contributions on Tuberculosis of the Knee-Joint and Its Surgical Treatment. PMID- 17859383 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859384 TI - I. The Dry Treatment for Open Wounds and Ulcers. PMID- 17859385 TI - II. Three Laparotomies on One Patient. Recovery. PMID- 17859386 TI - I. Delbet on Drainage of the Peritoneal Cavity. PMID- 17859387 TI - II. Kummell on the Surgery of the Gall-Bladder. PMID- 17859388 TI - III. Bardenheuer on Resection of the Articular Cavity of the Hip on account of Septic Epiphyseal Infection. PMID- 17859389 TI - IV. Vasilieff on the Development of Callus after Fractures of Long Bones. PMID- 17859391 TI - I. On Fibrous Stricture of the OEsophagus. PMID- 17859390 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859392 TI - II. Case of Cholecyst tomy for Gall-Stones. PMID- 17859393 TI - III. Empyema of Gall-Bladder; Cholecystotomy. PMID- 17859394 TI - I. Bergman on the Surgical Treatment of Diseases of the Brain. PMID- 17859395 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859396 TI - I. The Question of the Propriety of Resorting to Arthrotomy for Suturing Recent Simple Fractures of the Patella. PMID- 17859397 TI - II. In What Class of Wounds Shall We Use Drainage? PMID- 17859399 TI - IV. Dislocation of the Malar Bone. PMID- 17859398 TI - III. Cuneiform Osteotomy for Congenital Talipes Varus. PMID- 17859400 TI - I. Robb on Drainage in Pelvic Abdominal Surgery. PMID- 17859401 TI - II. Championniere on The Essentials of a Good Operating Room. PMID- 17859402 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859403 TI - Cervical Esophagogastric Anastomosis Following Subtotal Resection of the Esophagus for Carcinoma. PMID- 17859404 TI - Talc Granuloma-A Survey of Its Incidence and Significance. PMID- 17859405 TI - Complications of Gastro-intestinal Intubation. PMID- 17859406 TI - Inadvertent Gastro-ileostomy. PMID- 17859407 TI - The Inquiring Mind. PMID- 17859408 TI - Letter to the Editor. PMID- 17859409 TI - Cervical Esophagogastrostomy Following Resection of Supra-aortic Carcinoma of the Esophagus. PMID- 17859410 TI - Surgical Treatment of Duodenal Ulcer-Comparison of Results With and Without Vagotomy. PMID- 17859411 TI - "Categorically Inoperable" Carcinoma of the Breast. PMID- 17859412 TI - Exteriorization of the Canine Vesical Trigone for Experiments on the Kidney. PMID- 17859413 TI - Factors Inducing Renal Shut-down from Lysed Erythrocytes: An Experimental Study. PMID- 17859414 TI - The Effects of Ultraviolet Radiation on the Exposed Brain-Experimental Study. PMID- 17859415 TI - Disarticulation of an Innominate Bone (Hemipelvectomy) for Primary and Metastatic Cancer. PMID- 17859416 TI - One-stage Resection of Carcinoma of the Cervical Esophagus: Report of a Successful Case. PMID- 17859417 TI - The Mechanism of the Post-gastrectomy "Dumping" Syndrome. PMID- 17859418 TI - A Study of Mortality in a Burns Unit: Standards for the Evaluation of Alternative Methods of Treatment. PMID- 17859419 TI - The Surgery of Patent Ductus Arteriosus. PMID- 17859420 TI - Sigmoidovesical Fistulae Resulting from Diverticulitis of the Sigmoid Colon. PMID- 17859421 TI - Intussusception in Infants and Children: A Report of 143 Consecutive Cases. PMID- 17859423 TI - Varicose Veins: Further Findings based on Anatomic and Surgical Dissections. PMID- 17859424 TI - Chronic Stenosing Regional Enteritis-Surgical Pathology and Experience in Surgical Treatment. PMID- 17859425 TI - Further Experiences with Streptomycin Therapy in Peritonitis. PMID- 17859426 TI - Complete Duplication of the Large Bowel Treated by Subtotal Colectomy. PMID- 17859427 TI - Primary Carcinoma of the Duodenum: Report of a Case Surgically Resected. PMID- 17859428 TI - Isolated Fracture of the Atlas: Report of Two Cases. PMID- 17859429 TI - An Unusual Experience with the Miller-Abbott Tube. PMID- 17859430 TI - Spontaneous Internal Biliary Fistula: A Review of the Literature and Report of Two Cases. PMID- 17859431 TI - Emphysematous Acute Abdomen and Subcutaneous Emphysema from Intrarectal Operation. PMID- 17859433 TI - Presidential Address: Mission Accomplished-The Task Ahead. PMID- 17859432 TI - General Surgical Training and the Specialties. PMID- 17859434 TI - Cancer of the Breast. PMID- 17859435 TI - Malignant Melanoma: Forty Cases treated by Radical Resection. PMID- 17859436 TI - Development of New Methods for the Histochemical Demonstration of Hydrolytic Intracellular Enzymes in a Program of Cancer Research. PMID- 17859437 TI - Surgical Treatment of Congenital Pulmonary Stenosis. PMID- 17859438 TI - An Experimental Evaluation of Certain Methods of Suturing the Thoracic Aorta. PMID- 17859439 TI - The Surgical Relief of Congestion in the Pulmonary Circulation in Cases of Severe Mitral Stenosis: Preliminary Report of Six Cases treated by Means of Anastomosis between the Pulmonary and Systemic Venous Systems. PMID- 17859440 TI - The Valsalva Maneuver: An Aid for the Contrast Visualization of the Aorta and Great Vessels. PMID- 17859441 TI - Surgical Treatment of Insidious Thrombosis of the Aorta: Report of Ten Cases. PMID- 17859443 TI - Tinical Evaluation of Two Tests for Incipient Thrombosis: Prothrombin Activity and Fibrinogen B of Lyons. PMID- 17859442 TI - Quantitative Studies on the Time Factor in Arterial Injuries. PMID- 17859444 TI - Physiologic Studies in Cases of Stricture of the Common Bile Duct. PMID- 17859445 TI - Intrahepatic Cholangiojejunostomy for Biliary Obstruction-Further Studies: Report of Four Cases. PMID- 17859447 TI - Intestinal Obstruction in the Newborn. PMID- 17859446 TI - Deperitonealization: Clinical and Experimental Observations. PMID- 17859448 TI - Gastro-intestinal Gas: Observations on Belching: During Anesthesia and Operations, Rapid Passage, and During Pyelography. PMID- 17859449 TI - Sphincter Preserving Operations for Rectal Carcinoma as Related to the Anatomy of the Lymphatics. PMID- 17859450 TI - Extension of Carcinoma of the Stomach into the Duodenum and Esophagus. PMID- 17859451 TI - The End Results of Complete Versus Intracapsular Removal of Acoustic Tumors. PMID- 17859452 TI - Streptomycin, Aureomycin and Chloromycetin: Experimental and Clinical Comparison. PMID- 17859453 TI - Postoperative Deaths. PMID- 17859454 TI - Radiation Burns, Including Vocational and Atomic Exposures. Treatment and Surgical Prevention of Chronic Lesions. PMID- 17859455 TI - The Circulation of the Small Intestine: An Evaluation of its Revascularizing Potential. PMID- 17859456 TI - Herpes Zoster: A Surgical Procedure for the Treatment of Postherpetic Neuralgia. PMID- 17859457 TI - Clinical and Experimental Studies of Fluorescein Dyes with Special Reference to their Use for the Diagnosis of Central Nervous System Tumors. PMID- 17859458 TI - The Clinical Use of Radioactive Phosphorus in the Surgery of Brain Tumors. PMID- 17859459 TI - Evaluation of Total Sympathectomy. PMID- 17859460 TI - The Use of Bacitracin in Experimental Clostridium Welchii Infection in Guinea Pigs. PMID- 17859461 TI - Postoperative Nitrogen Loss A Comparison of the Effects of Trauma and the Caloric Readjustment. PMID- 17859462 TI - Minimum Postoperative Maintenance Requirements for Parenteral Water, Sodium, Potassium, Chloride and Glucose. PMID- 17859463 TI - The Metabolic Fate of the Infused Erythrocyte. PMID- 17859464 TI - An Evaluation of Oxygen Therapy. PMID- 17859465 TI - Sources of Error in Oximetry. PMID- 17859466 TI - The Experimental Study of Flash Burns. PMID- 17859467 TI - Blood Stasis in the Lungs as a Factor in the Etiology of Postoperative Pulmonary Complications. PMID- 17859468 TI - Elliptical Anastomosis in Urologic Surgery. PMID- 17859469 TI - The Pathogenesis of Hyperthyroidism. PMID- 17859470 TI - Transmetatarsal Amputation for Infection or Gangrene in Patients with Diabetes Mellitus. PMID- 17859472 TI - The Place of Research in a Surgical Training Program. PMID- 17859471 TI - Recurrence of Gastric Ulcer after Complete Vagotomy. PMID- 17859473 TI - Diverticulitis of the Colon. PMID- 17859474 TI - The Full-time Teacher of Surgery. PMID- 17859475 TI - General Surgery. PMID- 17859476 TI - The Necessity for Accurate Evaluation in Surgery. PMID- 17859477 TI - Psychiatry and Surgery. PMID- 17859478 TI - Valvular Anastomosis of the Heart Cavities. PMID- 17859479 TI - Technic of Resection of Coarctation of the Aorta with Aid of New Instruments. PMID- 17859481 TI - Lymphatic Metastases of Carcinoma of the Colon and Rectum. PMID- 17859480 TI - Carcinoma of the Thyroid Gland. PMID- 17859482 TI - Endometriosis. PMID- 17859483 TI - The Surgical Treatment of Familial Polyposis of the Colon: A Report of Seven Cases, Six in One Family. PMID- 17859484 TI - Disruption of Abdominal Wounds. PMID- 17859485 TI - Delayed Suture of Sensory Nerves of the Hand. PMID- 17859486 TI - Congenital Diverticulum of the Posterior Hypopharynx Simulating Atresia of the Esophagus. PMID- 17859487 TI - Retroperitoneal Hemorrhage following Lumbar Sympathetic Block during Treatment with Dicumarol: Report of a Fatality. PMID- 17859488 TI - Utilization of the Round and Falciform Ligaments as a Peritonealizing Structure in Surgery of the Upper Abdomen. PMID- 17859490 TI - A Two-Rib Incision for a Subtotal Esophagectomy. PMID- 17859489 TI - The Significance of Relaxed Inguinal Rings. PMID- 17859491 TI - "Abdominal Apoplexy" Complicated by Mesenteric Venous Thrombosis: Report of a Case. PMID- 17859492 TI - Aneurysm of the Splenic Artery: Report of Two Cases. PMID- 17859493 TI - Simplified Dermatome for Split Thickness Grafts. PMID- 17859494 TI - Anesthesia and the Old-Time Shotgun Prescription. PMID- 17859495 TI - The Surgical Treatment of Cholelithiasis. PMID- 17859496 TI - The Problem of Thromboembolism. PMID- 17859497 TI - The Surgical Conscience. PMID- 17859498 TI - Letter to the Editor. PMID- 17859499 TI - The Responsibility of Hospitals and Their Surgical Staffs to Residents. PMID- 17859500 TI - Vagus Section in the Treatment of Gastrojejunal Ulcer. PMID- 17859502 TI - THE ARMY MEDICAL SERVICE PROFITS BY PAST EXPERIENCE. PMID- 17859506 TI - Danger of Implanting Tumor Cells in Human Beings for the Purpose of "Immunization". PMID- 17859504 TI - A Four and One-Half Year Analysis of Tantalum Gauze Used in the Repair of Ventral Hernia. PMID- 17859507 TI - Foreword. PMID- 17859509 TI - The Deacon's Masterpiece, as the Surgeon Sees It. PMID- 17859510 TI - Letter to the Editor. PMID- 17859511 TI - Carcinoid Tumor of the Rectum. PMID- 17859515 TI - I. The Present Position of Antiseptic Surgery. PMID- 17859513 TI - Resection of the Superior Hypogastric Plexus for Dysmenorrhea. PMID- 17859516 TI - II. Rupture of the Joint-Capsule and Extensive Contusions as Contraindications to Immediate Suturing of Fracture of the Patella. PMID- 17859517 TI - III. A New Operation for Spasmodic Wry-Neck. PMID- 17859518 TI - I. Macewen on the Cure of Aneurism by Inducing the Formation of White Thrombi Within the Sac. PMID- 17859519 TI - II. Krecke on the Surgical Treatment of Circumscribed and General Peritonitis Starting from the Vermiform Appendix. PMID- 17859520 TI - III. Recent Russian Contributions to the Surgery of the Larynx. PMID- 17859521 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859523 TI - IV. A Case of Brain Tumor. PMID- 17859522 TI - III. A Case of OEsophagotomy for Removal of an Impacted Foreign Body. PMID- 17859524 TI - I. Melchior on the Conservative Treatment of Haemarthrosis of the Knee-Joint. PMID- 17859525 TI - II. Results of Knee Resections in Adults for Tuberculosis, in the Tuebingen Clinic. PMID- 17859526 TI - III. Kocher on the Treatment of Old Dislocations of the Shoulder-Joint. PMID- 17859527 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859528 TI - I. Circular Enterorrhaphy by a New Method. PMID- 17859529 TI - II. A Case of Partial Excision of the Sternum on Account of Sarcoma. PMID- 17859530 TI - I. The Inflammatary Process; The Relation of Bacteria to Inflammation; Surgical Infection. (The First Mutter Lecture, Series of 1890-1). PMID- 17859531 TI - I. Horsley on the Surgery of the Central Nervous System. PMID- 17859533 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859532 TI - II. Some Recent Cranial Surgery. PMID- 17859534 TI - I. On the Pathology of Appendicitis. PMID- 17859535 TI - II. The Indications for Early Laparotomy in Appendicitis. PMID- 17859536 TI - III. The Indications for Early Laparotomy in Appendicitis. PMID- 17859538 TI - V. The Operative Technique of Appendicitis. PMID- 17859537 TI - IV. The Technique of Operations for the Relief of Appendicitis. PMID- 17859539 TI - VI. Wound Infection and Suppuration. (The Second Mutter Lecture, Series of 1890 91). PMID- 17859540 TI - I. Sponges and Their Use in Surgery. PMID- 17859541 TI - II. Operation for Complete Prolapse of the Rectum after the Method Recommended by Dr. John B. Roberts. PMID- 17859542 TI - III. Simultaneous Distal Ligation of the Right Common Carotid and Right Subclavian Arteries for Supposed Innominate Aneurism. PMID- 17859543 TI - IV. The Propriety of, and the Indications for, the Resection of the Appendix Vermiformis During the Quiescent Stages of Chronic Relapsing Appendicitis. PMID- 17859544 TI - V. On the Resection of the Appendix Vermiformis During the Quiescent Stage of Chronic Relapsing Appendicitis. PMID- 17859546 TI - VII. Report of Three Fractures with Fatal Termination. PMID- 17859545 TI - VI. Instances of Foreign Bodies Lodged in the Body. PMID- 17859547 TI - VIII. Pyogenic Organisms. (Third Mutter Lecture, Series of 1890-91). PMID- 17859548 TI - I. The Germ Theory of Syphilis from a Clinical Point of View. PMID- 17859549 TI - II. A New Method of doing Jobert's Operation. PMID- 17859550 TI - III. The Operative Treatment of Head Injuries. PMID- 17859551 TI - IV. Note on Acute Periostitis of Femur in Children. PMID- 17859552 TI - V. The Results of the Absorption of the Products of Wound Infection. (Fourth Mutter Lecture, Series of 1890-91). PMID- 17859554 TI - Letters to the Editor. PMID- 17859553 TI - Letters to the Editor. PMID- 17859555 TI - More Accurate Estimation of the Extent of Gastric Resection. PMID- 17859556 TI - Address of the President. PMID- 17859557 TI - The Transfer of Surgical Experience. PMID- 17859558 TI - Letter to Editor. PMID- 17859559 TI - Editorial: The Surgical Treatment of Cancer. PMID- 17859560 TI - Editorial: The Surgeon and Preventive Psychiatry. The Problem of the "Surgical Addict". PMID- 17859562 TI - Comment on the Critique. PMID- 17859561 TI - Critique of "A Study of the Deaths Associated with Anesthesia and Surgery". PMID- 17859563 TI - Editorial: A Look at the Medical Specialty Boards. PMID- 17859564 TI - Letter to the Editor. PMID- 17859565 TI - The Stomach in Bed Three. PMID- 17859566 TI - Letter to the Editor. PMID- 17859567 TI - Presidential Address: The Nature of Discovery. PMID- 17859568 TI - General Education in Surgery. PMID- 17859570 TI - Keeping Abreast: An Item in Hospital Budgets. PMID- 17859569 TI - The Postcholecystectomy Syndrome. PMID- 17859572 TI - Evarts A. Graham. PMID- 17859571 TI - Hemorrhage as a Complication of Gastro-enterostomy. PMID- 17859573 TI - Editorial. PMID- 17859575 TI - Seventh International Cancer Congress: Applications and Travel Allotments. PMID- 17859574 TI - Secondary Operations and the Biliary Tract. PMID- 17859576 TI - Presidential Address-As It Was In The Beginning. PMID- 17859577 TI - Studies in Wound Healing: II. The Role of Granulation Tissue in Contraction. PMID- 17859578 TI - Medical Center Hospitals and Postoperative Complications. PMID- 17859579 TI - I. Malignant Tumors of the Nasal Fossae. PMID- 17859580 TI - II. Meloplasty. PMID- 17859581 TI - III. On Omental Tumors Due to Adhesive Inflammation. PMID- 17859582 TI - IV. Impairment or Loss of the Sense of Smell as a Means of Diagnosis. PMID- 17859584 TI - I. Karewski on the Surgically Important Syphilomata. PMID- 17859585 TI - II. Case of Ruptured Kidney, with Remarks. PMID- 17859583 TI - V. Peritonitis.-Tests for Antiseptics. (Fifth Mutter Lecture, Series of 1890-91). PMID- 17859587 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859586 TI - III. Tetany-Tetanus. (Sixth Mutter Lecture, Series of 1890-91). PMID- 17859588 TI - I. The Supposed Curative Effect of Operations per u. PMID- 17859589 TI - I. The Supposed Curative Effect of Operations per se. PMID- 17859590 TI - II. Contribution to the Knowledge of Sarcoma. PMID- 17859591 TI - III. Report of a Case of Subclavian Aneurism, with Ligation of the Subclavian Cure. Report of a Case of Nephrorraphy. PMID- 17859592 TI - IV. Surgical Diseases of Microbic Origin. (Seventh Mutter Lecture, Series of 1890 91). PMID- 17859593 TI - I. Snow on the Reappearance of Cancer after Apparent Extirpation. PMID- 17859594 TI - II. Keegan on Rhinoplasty. PMID- 17859595 TI - I. The Initial Seats of Neoplasms and Their Relative Frequency. PMID- 17859596 TI - II. Drainage of Wounds with Special Reference to Drainage after Urethrotomy. PMID- 17859597 TI - III. Laparotomy for Gunshot Wounds of the Abdomen, With report of a Recent Successful Case. PMID- 17859598 TI - IV. The Treatment of Hydrocele by Carbolic Acid Injection. PMID- 17859600 TI - VI. Tuberculosis. (Eighth Mutter Lecture, Series of 1890-91). PMID- 17859599 TI - V. Note on Bromide of Ethyl as an Anaesthetic. PMID- 17859602 TI - II. Bryant on Internal Intestinal Strangulation and Obstruction. PMID- 17859601 TI - I. Gonnesco on Internal Retro-Peritoneal Herniae. PMID- 17859603 TI - I. Cysts of the Urachus. PMID- 17859605 TI - III. Case of Symmetrical Congenital Dislocation of the Head of Each Radius. PMID- 17859604 TI - II. The Biceps Cruris Muscle as it Relates to Diseases in and Around the Knee Joint. PMID- 17859606 TI - IV. Mixed and Secondary Infections. (Eighth Mutter Lecture, Series of 1890-91). PMID- 17859608 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859607 TI - Thornton's Recent Cases of Hepatic Surgery. PMID- 17859609 TI - I. On the Treatment of Traumatic Aneurisms, With Report of a Cured Case of Traumatic Aneurism of the Right Common Carotid Artery. PMID- 17859610 TI - II. Cases of Penetrating Stab and Gunshot Wound of the Abdomen. PMID- 17859611 TI - IV. Mixed and Secondary Infections. (Ninth Mutter Lecture, Series of 1890-91). PMID- 17859612 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859613 TI - The Effect of Antrectomy on Gastric Blood Flow. PMID- 17859614 TI - Visualization of the Pancreas by Aortography. PMID- 17859615 TI - Bovine Arterial Grafts : An Experimental Study. PMID- 17859616 TI - Transplantation Immunity: Some Properties of Induction and Expression. PMID- 17859617 TI - Results of Open Commissurotomy in Acquired Calcific Aortic Stenosis: Clinical and Hemodynamic Studies in Patients Operated upon With General Hypothermia. PMID- 17859618 TI - Hepatocholangiojejunostomy Roux en Y: An Alternate Method of Repair of Bile Duct Strictures. PMID- 17859619 TI - Cross-over Graft for Unilateral Occlusive Disease of the Ilio-Femoral Arteries. PMID- 17859621 TI - Primary Closure of the Common Duct. PMID- 17859620 TI - Intramural Diverticulitis. PMID- 17859622 TI - Adenocarcinoma of the Rectum: Incidence and Locations of Recurrent Tumor Following Present-day Operations Performed for Cure. PMID- 17859623 TI - Gaucher's Disease With Ascites: Response to Portacaval Shunt. PMID- 17859624 TI - Lymphangiosarcoma of the Edematous Extremity. PMID- 17859625 TI - Operative Correction of Pectus Carinatum (Pigeon Breast). PMID- 17859626 TI - Jacksonville Plan in Postgraduate Education : An Experiment in Graduate Surgical Education. PMID- 17859627 TI - Late Behavior of Arterial Grafts: Three- to Five-Year Follow up of Homografts and Synthetic Prostheses in Experimental Animals. PMID- 17859628 TI - Studies of the Dermis in Skin Homografts. PMID- 17859629 TI - Radial Styloidectomy and Styloidectomy Plus Bone Graft in the Treatment of Old Ununited Carpal-Scaphoid Fractures. PMID- 17859630 TI - Cusp Replacement and Coronary Artery Perfusion in Open Operations on the Aortic Valve. PMID- 17859631 TI - Investigation of, and Use of DiMethyl Siloxanes, Halogenated Carbons and Polyvinyl Alcohol, as Subcutaneous Prosthesis. PMID- 17859633 TI - Separation of Conjoined Thoracopagus Twins: Surgical Considerations. PMID- 17859632 TI - Abdominal Perfusion for Cancer Chemotherapy. PMID- 17859634 TI - Coarctation of the Abdominal Aorta and Renal Artery Stenosis Corrected by Surgical Treatment: The Importance of Individual Renal Function Tests in Selection of Proper Management. PMID- 17859635 TI - Study of the Role of 5-Hydroxytryptamine (Serotonin) and Histamine in the Pathogenesis of Pulmonary Embolism in Man. PMID- 17859636 TI - The Use of Hypotensive Anesthesia in Radical Mastectomy. PMID- 17859638 TI - Hospital Management of the Ishikawa Disaster Patients at the U. S. Army Hospital, Ryukyu Islands. PMID- 17859637 TI - Absorption Studies after the Insertion of Colon as a Substitute for Both the Stomach and the Esophagus. PMID- 17859639 TI - Emergency Use of Antegrade Aortography in Diagnosis of Acute Aortic Rupture. PMID- 17859640 TI - Surgical Repair of Ruptured Aneurysm of Sinus of Valsalva in Two Patients. PMID- 17859641 TI - A Note on the Fate of Skin Autografts and Homografts and on the Healing of Cutaneous Wounds in Hibernating Squirrels. PMID- 17859642 TI - Subcutaneous Emphysema: An Important Sign of Intra-abdominal Abscess. PMID- 17859643 TI - Hirschsprung's Disease with Skip Area. PMID- 17859644 TI - Subacute Granulomatous Thyroiditis: A Clinicopathologic Review. PMID- 17859645 TI - Elective Hypothermic Cardiac Arrest in Normothermic Animals. PMID- 17859646 TI - Comparative Reaction of Mersilene and Silk Sutures Implanted Within the Heart. PMID- 17859647 TI - Perfusion Technic for Surgery on the Aortic Valves. PMID- 17859648 TI - Studies of Coronary and Peripheral Blood Flow Following Hemorrhagic Shock, Transfusion and L-Norepinephrine. PMID- 17859649 TI - Arteriomesenteric Duodenal Obstruction Associated with Severe Peptic Ulcer Disease. PMID- 17859650 TI - Nephrotoxicity of Iodinated Contrast Media: Quantitative Effects of High Concentration Upon Glomerular and Tubular Functions. PMID- 17859651 TI - Varicose Veins of the Lower Extremity Secondary to Traumatic Arteriovenous Fistula: Late Results of War Injuries. PMID- 17859652 TI - Current Trends in the Surgical Treatment of Diverticulitis of the Colon: Review of Thirty-Seven Cases. PMID- 17859653 TI - Intramural Hematoma of the Duodenum and Jejunum: A Cause of High Intestinal Obstruction-Report of Three Cases due to Trauma. PMID- 17859654 TI - Preduodenal Portal Vein Causing Duodenal Obstruction Associated with Pneumatosis Cystoides Intestinalis. PMID- 17859655 TI - Congenital Pyloric Atresia, a Rare Anomaly: Report of a Successful Case. PMID- 17859656 TI - Internal Jugular Aneurysm, Lymphocele and Axillary Arteriovenous Fistula Following a Bullet Wound. PMID- 17859658 TI - Right Hepatic Lobectomy for Carcinoma of the Gallbladder: A Five-Year Cure. PMID- 17859657 TI - Surgical Management of Reflux Esophagitis. PMID- 17859659 TI - Mechanism of Antral Regulation of Gastric Secretion: Discontinuous Cross Circulation. PMID- 17859660 TI - Rupture of the Thoracic Aorta due to Nonpenetrating Trauma. PMID- 17859661 TI - Primary Malignant Tumors of the Chest Wall (Excluding Primary Cutaneous Neoplasms). PMID- 17859662 TI - Tumor Cell Contamination of the Surgical Wound: Experimental and Clinical Observations. PMID- 17859663 TI - Simplified Treatment of Cancer of the Breast: Early Results of a Clinical Study. PMID- 17859664 TI - Disorders of the Biliary-Pancreatic System: Observations on Lymph Drainage in Jaundiced Patients. PMID- 17859665 TI - Spontaneous Rupture of the Splenic Vein During Pregnancy. PMID- 17859666 TI - Unexpected Rupture of the Stomach in the Postpartum Period: A Case Report. PMID- 17859667 TI - Electrical Burns: A Case Report. PMID- 17859668 TI - Treatment of Superior Sulcus Tumor by Irradiation Followed by Resection. PMID- 17859669 TI - Cirrhosis of the Liver and Bleeding Esophageal Varices, A Comparison of Operative and Nonoperative Treatment. PMID- 17859670 TI - Preoperative Cholangiography. PMID- 17859671 TI - Serum Amylase Levels in Experimental Intestinal Obstruction: Does Small Bowel Necrosis Cause a Rise in Serum Amylase? PMID- 17859672 TI - Presidential Address: On the Need for Continuity in Medical Education. PMID- 17859673 TI - Clinical Assessment of the Efficiency and Durability of Direct Vision Annuloplasty. PMID- 17859674 TI - Influence of Hypothermia on Pancreatic Function. PMID- 17859675 TI - Acidosis of Hypothermia. PMID- 17859676 TI - Breast Adjuvant Chemotherapy: Effectiveness of Thio-Tepa (Triethylenethiophosphoramide) as Adjuvant to Radical Mastectomy for Breast Cancer. PMID- 17859677 TI - Evaluation of Pericardial Monocusps as Aortic Valve Replacements. PMID- 17859678 TI - Some Hazards of Suction Drainage of Large Skin Flaps. PMID- 17859679 TI - Obstruction of the Small Bowel: An Evaluation of Pathology and Treatment. PMID- 17859680 TI - John of Gaddesden. PMID- 17859681 TI - Multiple Polyposis of the Small Intestine. PMID- 17859682 TI - Ruptured Abdominal Aortic Aneurysms: Problems of Diagnosis and Management. PMID- 17859683 TI - Two-stage Resection of the Sigmoid. PMID- 17859684 TI - Pseudocysts of the Pancreas. PMID- 17859685 TI - Etiology of Femoral Hernia. PMID- 17859687 TI - Surgical Anatomy of Adrenal Glands. PMID- 17859686 TI - Volvulus of the Right Colon. PMID- 17859688 TI - Cancer of the Breast: Personal Experience with 185 Patients. PMID- 17859689 TI - Curriculum Vitae. PMID- 17859690 TI - Malignant Melanoma: A Study of 217 Cases: Part I: Epidemiology. PMID- 17859691 TI - Malignant Melanoma: A Study of 217 Cases: Part II: Treatment Effect. PMID- 17859692 TI - Re-evaluation of Scrub Technic for Preoperative Disinfection of the Surgeon's Hands. PMID- 17859693 TI - Metabolic Response to Thermal Trauma: II. Nutritional Studies with Rats at Two Environmental Temperatures. PMID- 17859694 TI - Lateral Pharyngeal Diverticula. PMID- 17859695 TI - Surgical Treatment of Portal Hypertension According to State of Intrahepatic Circulation. PMID- 17859696 TI - Survival of an Infant Following Massive Resection of the Small Intestine. PMID- 17859697 TI - Diverticulosis and Diverticulitis of the Vermiform Appendix. PMID- 17859698 TI - Specialization in General Surgery: I. PMID- 17859699 TI - Experimental Pancreatitis A Possible Etiology of Postoperative Pancreatitis. PMID- 17859700 TI - Carcinoma of the Ovary: A Report of 106 Cases: I. A Further Effort at Pathological Differentiation. PMID- 17859701 TI - Carcinoma of the Colon Rectum and Anus. PMID- 17859702 TI - Villous Adenomas of the Rectum and Sigmoid Colon with Severe Fluid and Electrolyte Depletion. PMID- 17859703 TI - Experimental Study of the Effect of Grafts in the Common Duct on Biliary and Hepartic Function. PMID- 17859704 TI - Evaluation of the Use of a Temporary Percutaneous Endotracheal Catheter in the Treatment and Prevention of Postoperative Pulmonary Complications. PMID- 17859705 TI - Surgical Correction of Anomalous Pulmonary Venous Connection. PMID- 17859706 TI - Relationship of Tetracycline to Carcinoma. PMID- 17859707 TI - Indications for and the Results of the Surgical Treatment of Regional Enteritis. PMID- 17859708 TI - Serotonin Release Following Instillation of Hypertonic Glucose into the Proximal Intestine. PMID- 17859709 TI - Alterations in Thoracic Duct Lymph Flow in Hepatic Cirrhosis: Significance in Portal Hypertension. PMID- 17859710 TI - Clinical Experience with a New Operation (Modified Duhamel Procedure) for Hirschsprung's Disease. PMID- 17859711 TI - Recurrent Inguinal Hernia. PMID- 17859712 TI - Gastro-Pseudo-Esophagoplasty Following Total or Subtotal Mediastinal Esophagectomy: Evaluation of Antithoracic or Presternal Gastroesophageal Reconstruction. PMID- 17859713 TI - Postprostatectomy Bleeding: Analysis of Consequences of Control by Clotting Agents and Hypothermia. PMID- 17859714 TI - Successful Surgical Management of Through-and-Through Stab Wound of the Aortic Arch. PMID- 17859715 TI - von Willebrand's Disease : A Cause for Massive Postoperative Bleeding-Report of a Case. PMID- 17859716 TI - Spontaneous Regression of Pulmonary Metastases from Hypernephroma. PMID- 17859717 TI - Occluded Mesenteric Veins: Site of Growth and Elaboration of Bacteria in Intestinal Strangulation Obstruction. PMID- 17859718 TI - Effect of Chloramphenicol, Human Gamma Globulin and Burn Convalescent Serum on the Late Deaths of Burned Mice. PMID- 17859719 TI - The Gunfighter's Wound. PMID- 17859720 TI - Consideration of the Factors Responsible for Stomal Obstruction Following a Billroth I Anastomosis. PMID- 17859722 TI - An Aspect of Internal Mammary Metastases from Carcinoma of the Breast. PMID- 17859721 TI - Treatment of Early Mammary Carcinoma: A Cooperative International Study. PMID- 17859723 TI - Pulmonary Diffusion Studies in Patients Undergoing Nonthoracic, Thoracic and Cardiopulmonary Bypass Procedures. PMID- 17859724 TI - Neurologic Changes Following Profound Hypothermia. PMID- 17859725 TI - Chemotherapy of Malignant Brain Tumors Using Regional Perfusion: I. Technic and Patient Selection. PMID- 17859726 TI - Adenoid Cystic Carcinoma of Seromucous Glands of the Head and Neck. PMID- 17859727 TI - Serum Transaminase Changes in Severe Burns. PMID- 17859728 TI - Fecal Fistulas of the Scrotum in Children Secondary to Ruptured Appendicitis. PMID- 17859729 TI - Multiple Uses of a Left Ventricular Vent in Open-Heart Surgery. PMID- 17859730 TI - Factors Affecting Hepatic Vascular Resistance in the Perfused Liver. PMID- 17859731 TI - Migration of Aortic Prosthesis into the Duodenum: Case Report and Review. PMID- 17859732 TI - Giant Cystic Meconium Peritonitis. PMID- 17859733 TI - Observations on the Nature of Mucin Secreting Urachal Cystadenoma. PMID- 17859734 TI - Preliminary Report on a New Method of Surgical Management of Hydatid Cysts of the Lung. PMID- 17859736 TI - Presidential Address: The Davis Brothers of Birmingham and the Southern Surgical and Gynecological Association. PMID- 17859735 TI - Prevention of Brain Damage During Profound Hypothermia and Circulatory Arrest. PMID- 17859737 TI - Splenectomy in Treatment of Secondary Hypersplenism. PMID- 17859738 TI - In Vivo and In Vitro Assay for Drug Effect on Cancer Cells. PMID- 17859739 TI - Intramural Hematoma of the Duodenum. PMID- 17859740 TI - Translumbar Aortography: A Simple, Safe, Technic. PMID- 17859741 TI - Present Indication for the Use of Cardiopulmonary Bypass in Surgical Treatment of Mitral Stenosis. PMID- 17859742 TI - Union of Severed Arterial Trunks and Canalization Without Suture or Prosthesis. PMID- 17859743 TI - Clinical Experience with Management of the Infected Dacron Graft. PMID- 17859744 TI - Editorial. PMID- 17859745 TI - Effect of Intravenous Urea Upon the Fluid and Electrolyte Requirements Following Thermal Trauma: I. The Response of Rats to a Constant Intravenous Water Load Administered as 1) Buffered Isotonic Solution; 2) 4% Urea in 5% Dextrose in Water; and 3) 5% Dextrose in Water. PMID- 17859746 TI - I. The Treatment of Tuberculosis of Bones and Joints by Parenchymatous and Intra Articular Injections. PMID- 17859748 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859747 TI - II. Mixed and Secondary Infections. (Tenth Mutter Lecture, Series of 1890-91). PMID- 17859749 TI - II. Case of Caecal Hernia: Symptoms of Strangulation; Herniotomy; Wound of the Bowel; Suture; Recovery. PMID- 17859751 TI - Heidenhain on the Treatment of Senile Gangrene of the Lower Extremity. PMID- 17859750 TI - III. Suggestions as to the Technique of Intestinal Anastomosis. PMID- 17859753 TI - I. Studies upon Injuries of the Kidney, Nephrolithotomy and Nephrorrhaphy. PMID- 17859752 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859754 TI - I. The Surgical Management of Genitourinary Calculus. PMID- 17859756 TI - The Ultimate Results of Operations for Removal of the Uterus or its Appendages. PMID- 17859755 TI - II. Studies upon Niperies of the Kidney; Nephrolithotomy, and Nephrorraphy. Continued. PMID- 17859757 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859759 TI - II. Treatment of Compound Fractures. PMID- 17859758 TI - I. On the pathology, etiology and treatment of hip-joint disease in the light of present bacteriological and operative experience. PMID- 17859760 TI - III. Nephrotomy for the relief of sudden total suppression of urine occurring some time after nephrectomy: With the Report of a Successful Case. PMID- 17859761 TI - Plicque on Hysterical Coxalgia. PMID- 17859762 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859764 TI - II. The Crossed Suture. PMID- 17859763 TI - I. Intravenous Saline Infusion for Shock and Acute Anaemia. PMID- 17859765 TI - III. Cases of Appendicitis treated in Surgical Wards of the Cook County Hospital. PMID- 17859766 TI - IV. Case of Melano-Sarcoma in an Infant. PMID- 17859767 TI - I. Arnd on Methods and Results of Excision of Rectal Carcinoma. PMID- 17859768 TI - II. Landerer on the Treatment of Fractures. PMID- 17859769 TI - III. Lucas-Championiere on Radical Cure of Hernia in Women. PMID- 17859770 TI - IV. Korte on the Surgery of the Gall-Passages and the Liver. PMID- 17859772 TI - I. Obturator Dislocation. PMID- 17859771 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859774 TI - I. Woelfler on the Surgical Treatment of Goitre. PMID- 17859773 TI - II. Knee-joint Exsection. PMID- 17859775 TI - II. Poore's contribution to the Statistics of Operations upon Tuberculous Hip joints. PMID- 17859776 TI - III. Whitman on Radical Cure of Confirmed Flatfoot. PMID- 17859777 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859778 TI - Chapter II Ultraviolet Radiation in the Operating Room: A Historical Review. PMID- 17859779 TI - Chapter VI Epidemiological Considerations. PMID- 17859781 TI - Chapter III Organization, Methods, and Physical Factors of the Study. PMID- 17859780 TI - Chapter VII Summary. PMID- 17859783 TI - Chapter V Bacteriologic Studies. PMID- 17859782 TI - Chapter IV Factors Influencing the Incidence of Wound Infection. PMID- 17859784 TI - Chapter I Introduction. PMID- 17859785 TI - Remedial Operation for Severe Postgastrectomy Symptoms (Dumping): Emphasis on an Antiperistaltic (Reversed) Jejunal Segment Interpolated between Gastric Remnant and Duodenum and Role of Vagotomy. PMID- 17859786 TI - Prosthetic Substitution of Thoracic Esophagus in Puppies: Use of Marlex Mesh with Collagen or Anterior Rectus Sheath. PMID- 17859787 TI - Gastric Homotransplantation in Dogs: Response to Histamine and Meat Stimulation and Immunosuppressive Therapy with Azathioprine and Prednisolone. PMID- 17859789 TI - Role of Hepatic Arterial Blood Flow and Hepatic Nerves on Renal Circulation and Function: I. Acute Studies in the Dog. PMID- 17859788 TI - Homotransplantation of the Heart in Puppies Under Profound Hypothermia: Long Survival Without Immunosuppressive Treatment. PMID- 17859790 TI - Effect of Operative Trauma Upon Renal Function in Older Patients. PMID- 17859791 TI - Repair of Hepatic and Superior Mesenteric Artery Injury: Patency Demonstrated by Aortography. PMID- 17859792 TI - Alterations in Femoral Blood Flow and Resistance Following Sympathetic Blockade: Hemodynamic Evaluation of Patients With and Without Arterial Occlusion by Dye Dilution Technic. PMID- 17859793 TI - A Rapid, Simple and Inexpensive Method of Measurement of Blood Volume and Hepatic Function Utilizing Rose Bengal I. PMID- 17859794 TI - Review of Criteria for the Selection of the Level for Lower Extremity Amputation for Arteriosclerosis. PMID- 17859796 TI - Emergency Operation for Acute Cerebral Ischemia Due to Carotid Artery Obstruction:. PMID- 17859795 TI - Sympathetic Nerve Depletion in Severe Thermal Injury. PMID- 17859797 TI - Head-Down (Trendelenburg) Position for Treatment of Irreversible Shock: Experimental Study in Rats. PMID- 17859798 TI - Duodenal Duplication: Case Report and Literature Review. PMID- 17859799 TI - Rupture of Duodenum following Blunt Trauma: Report of a Case with Avulsion of Papilla of Vater. PMID- 17859800 TI - Treatment of Traumatic Hemobilia. PMID- 17859801 TI - Treatment of Exsanguinating Rupture of the Right Lobe of the Liver by Ligation of the Main Hepatic Artery:. PMID- 17859802 TI - Mesenteric Venous Thrombosis Following Splenectomy: Report of Two Cases. PMID- 17859803 TI - Resection of the Superior Mesenteric Vein and Replacement with a Venous Autograft During Pancreaticoduodenectomy: Case Report. PMID- 17859804 TI - Technic of Pyloroplasty for Duodenal Ulcer: Anterior Hemipylorectomy for Drainage of the Stomach. PMID- 17859805 TI - Hyperglycemic Coronary Perfusion: Effect of Hypothermia on Myocardial Function During Cardiopulmonary Bypass. PMID- 17859806 TI - Editorial. PMID- 17859807 TI - Association of primary neoplasms of the small intestine with other neoplastic growths. PMID- 17859808 TI - "Hidden acidosis" in experimental shock. PMID- 17859809 TI - Surgical Management of Tetralogy of Fallot in Children under Age Four. PMID- 17859810 TI - Carcinoma of the extrahepatic bile ducts. PMID- 17859811 TI - I. Treatment of Fractures of the Lower End of the Humerus and of the Base of the Radius. PMID- 17859812 TI - II. Hydrocele in the Female: With a Report of Fourteen Cases. PMID- 17859813 TI - III. Fractures of the Neck of the Femur: With a Report of Twelve Cases Treated by the Thomas Hip-Splint. PMID- 17859814 TI - IV. Fibroid Tumors of the Uterus. PMID- 17859815 TI - The Immediate and Ultimate Results of Vaginal Hysterectomy for Cancer of the Uterus. PMID- 17859816 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859817 TI - II. Cases of Operation in Spina Bifida and Encephalocele. PMID- 17859818 TI - III. Abscess or Aneurism. PMID- 17859819 TI - IV. Is Amputation justified in Coxitis. PMID- 17859820 TI - V. Note on the Dissection of a Case of Lumbar Hernia. PMID- 17859821 TI - I. Surgery of the Gall Bladder and Liver. PMID- 17859822 TI - II. Woelfler, on the Surgical Treatment of Goitre. PMID- 17859823 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859825 TI - I. Experimental Research on the Implantation of the Ureters into the Rectum. PMID- 17859824 TI - I. Surgery of the Tongue. PMID- 17859826 TI - II. Conditions demanding Excision of the Globe of the Eye. PMID- 17859827 TI - I. Schede's cases of Spinal Surgery. PMID- 17859828 TI - II. Kubler on Extirpation of Aneurism. PMID- 17859830 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859829 TI - III. Woelfler on the Surgical Treatment of Goitre, concluded. PMID- 17859831 TI - I. Laminectomy for Pott's Paraplegia. PMID- 17859833 TI - III. Musculo-spiral Paralysis complicating Fracture of the Humerus. PMID- 17859832 TI - II. The Treatment of Gangrenous Hernia. PMID- 17859835 TI - II. Lovett on the Relative Merits of Intubation and Tracheotomy for Diphtheritic Croup. PMID- 17859834 TI - I. Czerny on the Present State of the Surgery of the Gall-bladder. PMID- 17859836 TI - III. The Operating Pavilion of the New General Hospital at Hamburg. PMID- 17859837 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859838 TI - I. On the Treatment of Flat-foot. PMID- 17859840 TI - I. Observations upon Hernia at the last Meeting of the Italian Surgical Society. PMID- 17859839 TI - II. Case of Jacksonian Epilepsy, relieved by Trephining. PMID- 17859841 TI - II. Schede on the Extirpation of the Carcinomatous Uterus by the Sacral Route. PMID- 17859843 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859842 TI - III. Boldt on Vaginal Hysterectomy for Cancer of the Uterus. PMID- 17859844 TI - I. The Radical Cure of Hernia. PMID- 17859845 TI - II. Upward Dislocations of the Hip. PMID- 17859846 TI - I. The Comparative Value of Tracheotomy and Intubation for the Relief of Acute Laryngeal Stenosis in Children. PMID- 17859848 TI - III. Chipault on the Surgery of the Spinal Cord. PMID- 17859847 TI - II. Cerebral Surgery at the last Congress of Italian Surgeons. PMID- 17859849 TI - IV. Czerny's Recent Experience in the Operative Treatment of Carcinoma of the Rectum. PMID- 17859850 TI - V. Boisleux on Intraligamentous Elytrotomy. PMID- 17859851 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859852 TI - Presidential address: "we cannot escape history". PMID- 17859854 TI - Mondor's Disease (Phlebitis of the Thoracoepigastric Vein). PMID- 17859853 TI - Spontaneous retroperitoneal hemorrhage complicating anticoagulant therapy. PMID- 17859856 TI - Editorial. PMID- 17859855 TI - Intrahepatic Arteriovenous Fistulas between the Hepatic Artery and Portal Vein. PMID- 17859857 TI - Letters to the editor. PMID- 17859858 TI - Pentapeptide and Insulin Stimulated Gastric Acid Secretion in Patients with Duodenal Ulcer before and after Selective Gastric Vagotomy and Antrum Drainage: A Comparison with Results Obtained from Studies before and after Parietal Cell Vagotomy with No Drainage Procedure. PMID- 17859859 TI - Pentapeptide and insulin stimulated gastric Acid secretion in patients with gastric and duodenal ulcer. PMID- 17859860 TI - Letter to the editor. PMID- 17859861 TI - Letters to the editor. PMID- 17859862 TI - Penetrating wounds of great vessels. AB - Thirty-six patients with penetrating wounds of the great vessels treated at Grady Memorial Hospital during a 7-year period were reviewed. In more than 50% of the cases, diagnosis of the injury was made at the time of emergency thoracotomy for massive bleeding. In the remaining patients the diagnosis was suspected: 1) when the pulse distal to the vascular injury was absent or weak; 2) when the patient had symptoms and signs of impaired central nervous system perfusion; 3) when the missile had traversed the mediastinum and there was roentgenographic evidence of widening of the mediastinal shadow; or, 4) when a new murmur appeared. In all suspected cases with great vessel injury, the diagnosis was confirmed arteriographically. Arteriography in such patients should be performed to define the type and site of vascular injury so that its repair can be properly planned. Twenty-nine patients recovered from their injury, 6 succumbed as a result of it and 1 required midforearm amputation following repair of a subclavian artery and vein injury. Most of these patients underwent autotransfusion which greatly contributed to their successful outcome. Local temporary shunt was used for protection of the spinal cord and/or brain when impairment of their perfusion was required for the repair of the vascular wounds. PMID- 17859863 TI - I. Contribution to the Study of Amputations at the Hip-Joint. PMID- 17859864 TI - III. On the Operative Treatment of Hernia. PMID- 17859865 TI - II. Notes on Forcible Over-Correction in the Treatment of Flat-Foot. PMID- 17859866 TI - IV. Cases of Arterio-venous Aneurism of the Auxiliary Artery and Vein of fourteen years duration. PMID- 17859868 TI - VI. Strangulated Obturator Hernia. PMID- 17859867 TI - V. Expert Examinations and Testimony in Railway Cases. PMID- 17859869 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 23d, 1892. PMID- 17859870 TI - I. The Surgery of the Hypertrophied Prostate. PMID- 17859871 TI - II. Mironow on the Question of Asepsis in Laparotomy. PMID- 17859873 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859872 TI - III. Cranio-Cerebral Topography and its Surgical application. PMID- 17859874 TI - I. Report of a Case of Tumor of the Left Frontal Lobe of the Cerebrum; Operation; Recovery. PMID- 17859875 TI - II. A Method of Treating Compound Fractures. PMID- 17859876 TI - III. Vegetable Plates in Bowel and Stomach Surgery; A Discussion of the Proper Technique. PMID- 17859877 TI - IV. The Relations of the Gross Anatomy of the Vermiform Appendix to some Features of the Clinical History of Appendicitis. PMID- 17859878 TI - V. Urethrectomy, Partial or Complete, as a Method for Radical Treatment of Rupture of the Urethra, Fistula, or Organic Stricture. PMID- 17859879 TI - VI. Report of Seven Cases of Acute Axillary Suppuration of Unusual Severity, Treated by Extensive Excision of the Inflamed Tissues. PMID- 17859881 TI - I. Gueilliot on the Contagion of Cancer. PMID- 17859880 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, December 14, 1892. PMID- 17859883 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859882 TI - II. Iverson on Peri-Uterine Suppuration. PMID- 17859884 TI - Mental Symptoms Following Upon Use of Continuous Supra-Pubic Drainage of the Bladder. PMID- 17859885 TI - I. A Proposed New Method of Operating for the Radical Cure of Inguinal Hernia. PMID- 17859886 TI - II. The Accidents Which May Follow Removal of Portions of the Omentum in Operations for Hernia. PMID- 17859887 TI - III. Healing Under a Moist Blood-Clot in Accidental Wounds. PMID- 17859889 TI - V. A Contribution to the Anatomy of Congenital Equino-Varus. PMID- 17859888 TI - IV. Disease in the Sacro-Iliac Articulation. PMID- 17859890 TI - VI. Total Excision of the Lower Jaw for Malignant Disease. PMID- 17859891 TI - VII. Gradual Auto-Inoculation as a Factor in the Production of Immunity from the Effects of Septic Infection. PMID- 17859892 TI - VIII. A New and Rapid Method for Hysterectomy. PMID- 17859894 TI - X. A Case of Large Aneurism of the External Iliac Artery Apparently Cured by Macewen's Method of Needling. PMID- 17859893 TI - IX. A Case of Jejunostomy for Inoperable Cancer of the Stomach. PMID- 17859895 TI - XI. A Case of Cured Aneurism of the Abdominal Aorta Simulating a Solid Tumor. PMID- 17859896 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 11, 1893. PMID- 17859897 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 25, 1893. PMID- 17859898 TI - I. The Evolution of the American Surgeon. PMID- 17859899 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859900 TI - I. On the Value of Internal Medication in the Treatment of Malignant Disease. PMID- 17859901 TI - II. The Use and Place of Caustics in the Treatment of Cancer. PMID- 17859902 TI - III. The Domain of the Knife in the Treatment of Carcinoma. PMID- 17859904 TI - V. Remarks on the Management of Suppuration Complicating Tuberculous Disease of the Bones and Joints. PMID- 17859903 TI - IV. A Study of Seventeen Cases of Empyema. PMID- 17859905 TI - VI. Tuberculous Epididymitis. PMID- 17859906 TI - VII. A Case of Laminectomy for Depressed Fracture of the Spine. PMID- 17859907 TI - VIII. A Case of Perineal Lithotrity, with some Remarks upon Dilatation of the Prostate. PMID- 17859908 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, February 8, 1893. PMID- 17859910 TI - II. Hawkins on Tubercular Peritonitis. PMID- 17859909 TI - I. Some Recent Contributions to the Surgery of the Stomach. PMID- 17859911 TI - III. Haegler on the Surgical Significance of Dust. PMID- 17859912 TI - IV. Postnikow on Gastroenterostomy in Two Stages. PMID- 17859913 TI - V. The Present State of Knowledge as to Carcinoma. PMID- 17859914 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859915 TI - I. Intracranial Neurectomy of the Fifth Nerve. PMID- 17859916 TI - II. Observations on the Mechanical Treatment of Hernia at the Hospital for Ruptured and Crippled of New York. PMID- 17859917 TI - III. The Radical Cure of Inguinal Hernia in the Male. PMID- 17859918 TI - IV. A Syllabus of Intestinal Surgery. PMID- 17859920 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 8, 1893. PMID- 17859919 TI - V. A New Method of Treating Non-malignant Strictures of the Rectum by Transplantation of Intestine. PMID- 17859921 TI - I. On Some Fallacies Inherent in the Parasitic Theories of the Etiology of Carcinoma. PMID- 17859923 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859922 TI - II. Williams on Papillomatous Tumors of the Ovaries. PMID- 17859925 TI - II. Case of Cancer of the Hepatic Flexure of the Colon Producing Intestinal Obstruction; Temporary Relief by an Artificial Anus; Later Re-establishment of the Continuity of the Bowel by Ileo-colostomy by Means of Murphy's Button. PMID- 17859924 TI - I. The Complications of Cholelithiasis. PMID- 17859926 TI - III. The Use of Air to Dilate the Bladder in Suprapubic Cystotomy. PMID- 17859928 TI - V. A Method for Obtaining a Skin-Flap from the Scalp and a Permanent Buried Vascular Pedicle for Covering Defects of the Face. PMID- 17859927 TI - IV. Appendicular Colic. PMID- 17859929 TI - VI. Metatarsalgia (Morton's Painful Affection of the Foot), with an Account of Six Cases Cured by Operation. PMID- 17859931 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, March 6, 1893. PMID- 17859930 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 22, 1893. PMID- 17859932 TI - I. Lister's Present Antiseptic Practice. PMID- 17859933 TI - II. Operations upon the Stomach and Intestines Performed in the Surgical Clinic at Heidelberg. PMID- 17859934 TI - III. Morris on Infective Ecphyaditis. PMID- 17859936 TI - Letters to the editor. PMID- 17859935 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859937 TI - Letters to the editor. PMID- 17859938 TI - Letters to the editor. PMID- 17859939 TI - Letters to the editor. PMID- 17859940 TI - Letters to the editor. PMID- 17859942 TI - Letters to the editor. PMID- 17859941 TI - Letters to the editor. PMID- 17859943 TI - Letters to the editor. PMID- 17859945 TI - III. Unilateral Laryngectomy: A Case of Excision of the Right Half of the Larynx for Carcinoma; Recovery; No Recurrence at the End of a Year. PMID- 17859944 TI - I. Separation of the Lower Femoral Epiphysis. PMID- 17859947 TI - V. Report of a Case of Volvulus of the Sigmoid Flexure of the Colon Successfully Reduced after Abdominal Section. PMID- 17859946 TI - IV. Report of a Case of Hydrencephalocele Subjected to Excision; Recovery. PMID- 17859948 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 12, 1893. PMID- 17859949 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 26, 1893. PMID- 17859950 TI - I. Chipault on the Surgery of the Spine and Spinal Cord. PMID- 17859951 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859952 TI - II. Ossifying Haematoma. PMID- 17859953 TI - I. A New Method of Direct Fixation of the Fragments in Compound and Ununited Fractures. PMID- 17859954 TI - II. The Present Position of the Surgery of the Hypertrophied Prostate. PMID- 17859955 TI - III. A Contribution to the Surgery of the Rectum. PMID- 17859956 TI - IV. Electrolysis in the Treatment of Fibrous Anchylosis. PMID- 17859957 TI - V. Ten Cases of Anchylosis of the Elbow Joint, after Treatment of Fracture of the Lower End of the Humerus, with the Fore-Arm in the Extended Position: Five Treated by Exsection, Four Treated by Infraction, and One Not Treated. PMID- 17859958 TI - VI. A Case of Pancreatic Cyst. PMID- 17859960 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859959 TI - Gleiss on Nerve Suturing. PMID- 17859961 TI - I. Hypertrophies and Degenerations of Cicatrices and Cicatricial Tissue. PMID- 17859962 TI - II. Surgical Treatment of Cervical, Thoracic and Abdominal Aneurism. PMID- 17859963 TI - III. The Importance to the Surgeon of Familiarity with the Bacillus Coli Communis. PMID- 17859964 TI - IV. On a Method of Making Intestinal Anastomosis, which will prevent Subsequent Contraction of the Orifices. PMID- 17859965 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, April 3, 1893. PMID- 17859966 TI - I. The Discussion on the Treatment of Uterine Fibro-myomata at the Recent French Congress of Surgery. PMID- 17859967 TI - II. Richelot on the Operative Technique of Vaginal Hysterectomy. PMID- 17859968 TI - III. Suggestions for Effecting Sphincterplasty After Amputation of the Rectum. PMID- 17859970 TI - The Question of Priority in Devising a Method for the Performance of Intra cranial Neurectomy of the Fifth Nerve. PMID- 17859969 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859971 TI - Infectious Appendicitis. PMID- 17859972 TI - A Contribution to the Surgery of the Gall Bladder. PMID- 17859973 TI - THE RESULTS OF PARTIAL AND COMPLETE OCCLUSION OF THE URETERS. PMID- 17859974 TI - ON THE FEASIBILITY OF INTRAPERITONEAL CYSTOTOMY, WITH THE REPORT OF A CASE. PMID- 17859975 TI - Report of a Case of Removal of a Malignant Polyp Springing from the Base of the Skull, in Which an Attempt was Made to Practice Senn's Proposed Method of Rendering the Operation Bloodless. PMID- 17859976 TI - Report of Cases of Operative Relief of Endocranial Haemorrhage. PMID- 17859977 TI - Operative Procedures in Advanced Age, Based on a Study of Sixty-five Cases Aged Seventy or More. PMID- 17859978 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, May 1, 1893. PMID- 17859979 TI - I. Porter on the Indications to be Drawn From the Urine as to the Safety of Anaesthetics. PMID- 17859980 TI - II. Krause on the Transplantation of Large Skin Flaps Without a Pedicle. PMID- 17859981 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859983 TI - The Results Obtained from the Use of Aniline Products in the Treatment of Carcinoma. PMID- 17859982 TI - Traumatisms and Traumatic Aneurisms of the Vertebral Artery and Their Surgical Treatment with the Report of a Cured Case. PMID- 17859984 TI - Some Critical Observations Upon Certain Forms of Spinal Injury. PMID- 17859986 TI - I. Czerny on Pelvic Operations by the Sacral Route. PMID- 17859985 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, May 10, 1893. PMID- 17859987 TI - II. Kummell on Resection of the Kidney. PMID- 17859988 TI - INDEX OF SURGICAL PROGRESS. PMID- 17859989 TI - I. Report of a Case of Anthrax. PMID- 17859990 TI - II. Gunshot Wounds of the Intestines; Clinical Report of Thirteen Cases; Remarks on the Diagnosis and Treatment. PMID- 17859991 TI - III. Gastrostomy by Witzel's Method for Primary Cancer of the OEsophagus. PMID- 17859992 TI - IV. A Case of Intra-peritoneal Rupture of the Bladder; Recovery After Laparotomy. PMID- 17859993 TI - V. Complete Dislocation of Patella, Reduced by Arthrotomy After Six Years. PMID- 17859994 TI - VI. Case of Acute Intermittent Hydronephrosis From Valvular Stricture of the Ureter. PMID- 17859996 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 11, 1893. PMID- 17859995 TI - VII. A Case of Fragilitas Ossium, With Multiple Fractures and Vicious Union; Deformities Corrected by Osteotomy. PMID- 17859997 TI - I. Klemm on the Treatment of Fractures Involving Joints. PMID- 17859998 TI - II. Sokoloff on Fibroma Arborescens of the Joints. PMID- 17859999 TI - I. A Mode of Controlling the Circulation Through the Abdominal Aorta. PMID- 17860000 TI - I. Cinnamic Acid in the Treatment of Tuberculosis. PMID- 17860002 TI - INDEX OF SURGICAL PROGRESS. PMID- 17860001 TI - II. Zoller on the Surgical Treatment of Hypospadias and Epispadias in the Male. PMID- 17860004 TI - III. Intracranial Neurectomy and Removal of the Gasserian Ganglion. PMID- 17860003 TI - II. Observations Upon Appendicitis. PMID- 17860005 TI - IV. Sarcoma of the Kidney; Its Operative Treatment. PMID- 17860007 TI - VI. The Extirpation of Aneurisms. PMID- 17860006 TI - V. Uretero-Ureteral Anastomosis-Uretero-Ureterostomy. PMID- 17860008 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 25, 1893. PMID- 17860009 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 8, 1893. PMID- 17860010 TI - I. The Surgical Treatment of Pulmonary Cavities. PMID- 17860011 TI - II. Observations upon Appendicitis. PMID- 17860012 TI - III. Entero-Anastomosis for Malignant Stenosis of the Digestive Tract. PMID- 17860013 TI - IV. A Case of Emphysematous Gangrene of the Hand Due to the Streptococcus Pyogenes and the Bacillus AErogenes Capsulatus: Recovery without Amputation. PMID- 17860014 TI - V. Gangrenous Cholecystitis. PMID- 17860015 TI - VI. Hypertrophy of the Omentum in Hernia. PMID- 17860016 TI - VII. An Improved Method of Brain Localization in Epilepsy. PMID- 17860017 TI - VIII. An Examination of the Influence of the Ilio-psoas Muscle upon the Rotation of the Thigh. PMID- 17860018 TI - IX. An Improved Lock for Paired Instruments. PMID- 17860020 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 22, 1893. PMID- 17860019 TI - X. A New Spigot Attachment to Facilitate Asepsis. PMID- 17860021 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, November 6, 1893. PMID- 17860022 TI - I. The Operative Treatment of Club-foot. PMID- 17860023 TI - II. Traumatic Separation of the Epiphysis of the Lower Extremity. PMID- 17860024 TI - III. Observations upon Appendicitis. PMID- 17860025 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, December 13, 1893. PMID- 17860026 TI - Operations for Rupture of Bladder. PMID- 17860028 TI - II. Dislocation of the Humerus Complicated by Fracture at or near the Surgical Neck, with a New Method of Reduction. PMID- 17860027 TI - I. Fibrous Stricture of the OEsophagus Treated by Gastrotomy and Retrograde Dilatation. PMID- 17860029 TI - III. Two Cases of Primary Intestinal Resection for Gangrene of Bowel from Strangulation. PMID- 17860030 TI - IV. Tapping of the Lateral Ventricles. PMID- 17860031 TI - V. Spontaneous Torsion of the Pedicle of Ovarian Tumors; with the Report of a Case of Rotated Ovarian Cyst with Extensive Intra-mural Haemorrhage. PMID- 17860032 TI - VI. The Operative Treatment of Non-microcephalic Idiocy. PMID- 17860033 TI - VII. Report of Cases of Surgery of the Urinary Bladder Involving Suprapubic Section. PMID- 17860034 TI - VIII. Report of a Case of Carcinoma of Ileum; Intestinal Obstruction Relieved by Anastomosis with a Murphy Button. PMID- 17860035 TI - IX. Observations upon Appendicitis. PMID- 17860036 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 10, 1894. PMID- 17860037 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860038 TI - I. On Traumatic Ruptures of the Ureter, with Report of a Case of Ruptured Ureter Followed by Nephrectomy in a Child. PMID- 17860039 TI - II. Strangulation of Testicle from Twist of the Spermatic Cord. PMID- 17860041 TI - IV. Observations upon Appendicitis. PMID- 17860040 TI - III. Contribution to the Study of Head Injuries, and of the Results of Trephining for Subdural Haemorrhage, Abscess of Brain, and Epilepsy. PMID- 17860042 TI - V. Some Surgical Thoughts on Appendicitis from a Clinical Stand-point. PMID- 17860043 TI - VI. A New Method of Closing the Canal in Radical Operation for Inguinal Hernia. PMID- 17860044 TI - VII. Note on the Value of Maceration in Ether and in Ether-Solution of Corrosive Sublimate for the Sterilization of Catgut. PMID- 17860045 TI - VIII. A Case of Primary Tuberculosis of the Laminae and Spinous Processes of the Vertebral Column. PMID- 17860046 TI - IX. Report of a Case of Haematophilia, with Death from Haemorrhage Following the Extraction of a Tooth. PMID- 17860047 TI - X. An Improved Aseptic Trephine. PMID- 17860048 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 24, 1894. PMID- 17860049 TI - I. The Treatment of Tuberculous Peritonitis. PMID- 17860051 TI - I. Cases of Ruptured Kidney. PMID- 17860050 TI - II. Wunderlich on Clinical Observations on the Effect of Chloroform and Ether Narcosis on the Kidneys. PMID- 17860052 TI - II. Report of Three Cases of Gangrenous Hernia subjected to Circular Enterorrhaphy. PMID- 17860053 TI - III. Fracture of the Lower Jaw with Separation of the Genial Tubercle. PMID- 17860054 TI - IV. Gastro-Enterostomy with Bone Plates. PMID- 17860055 TI - V. Two Cases of Laminectomy for Fracture of the Vertebrae with Compression of the Cord. PMID- 17860056 TI - VI. Report of Two Cases of Laminectomy, with a Tabulated Collection of Fifty-two Cases of Laminectomy of Recent Date. PMID- 17860057 TI - VII. Malignant Stenosis of Sigmoid Flexure of Colon, with Enormous Collection of Fruit-Stones above Stricture; Relieved by Colotomy. PMID- 17860058 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, Febuary 14, 1894. PMID- 17860059 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, Febuary 28, 1894. PMID- 17860061 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, March 5, 1894. PMID- 17860060 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, February 5, 1894. PMID- 17860062 TI - I. Immunity against Tetanus. PMID- 17860064 TI - III. Nasse on the Extirpation of the Shoulder, and its Value in the Treatment of Sarcoma of the Humerus. PMID- 17860063 TI - II. Goldmann on the After Course of Skin-Grafts Transplanted after the Method of Thiersch. PMID- 17860065 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860066 TI - I. A Study of 170 Cases of Cancer. PMID- 17860067 TI - II. Fischer on Suppurative Inflammations in the Subumbilical Space. PMID- 17860068 TI - II. Old Displacements of the Upper End of the Femur and their Treatment. PMID- 17860069 TI - III. Cases Illustrating the Use of a Mechanical Appliance to Correct the Deformity after Removal of Half of the Lower Jaw. PMID- 17860070 TI - IV. The Incision Made in the Abdominal Wall in Cases of Appendicitis, with a Description of a New Method of Operating. PMID- 17860072 TI - VI. A Case of Obstructive Hypertrophy of the Prostate Treated by Castration. PMID- 17860071 TI - V. Simultaneous Ligation of Both Internal Iliac Arteries for Hypertrophy of the Prostate Gland (Bier's Method). PMID- 17860073 TI - VII. Note on the Sterilization of Catgut by Boiling in Olive Oil. PMID- 17860074 TI - VIII. Intestinal Obstruction from Strangulation by an Adhesion Band; Recovery after Laparotomy. PMID- 17860075 TI - IX. Large Pseudo-Diverticulum of the Duodenum. PMID- 17860077 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 28, 1894. PMID- 17860076 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 14, 1894. PMID- 17860078 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, April 2, 1894. PMID- 17860079 TI - TRANSACTIONS OF THE SURGICAL SECTION OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Meeting of April 13, 1894. PMID- 17860080 TI - I. Lauenstein on Strangulation of the Testicle from Torsion of the Spermatic Cord. PMID- 17860081 TI - I. Treatment of Congenital Dislocation of the Hip. PMID- 17860082 TI - II. Treatment of Congenital Dislocation of the Hip. PMID- 17860083 TI - III. Report of Six Operations on the Spinal Cord for the Relief of Paraplegia. PMID- 17860084 TI - IV. Tuberculosis of the Breast. PMID- 17860085 TI - V. Venous Tumor of the Diploe. PMID- 17860086 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 11, 1894. PMID- 17860087 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 24. PMID- 17860088 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, May 7, 1894. PMID- 17860089 TI - I. Chaput on the Inosculation of the Ureters with the Intestine. PMID- 17860090 TI - II. On the Surgery and Physiology of the Spleen. PMID- 17860091 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860092 TI - I. Surgery of the Ureter. PMID- 17860093 TI - II. View of the Results thus far Obtained by the Use of Absorbable Plates in Effecting Visceral Approximation. PMID- 17860094 TI - III. The Operative Treatment of Old Unreduced and Irreducible Dislocations of the Hip. PMID- 17860095 TI - IV. Neudorfer's Method of Amputating Extremities, with a Report of Two Thigh Amputations. PMID- 17860096 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, May 9, 1894. PMID- 17860097 TI - Stern on the Statistics and Prognosis of Herniotomy in the Incarcerated Herniae of Early Childhood. PMID- 17860098 TI - I. Experimental Researches in Infective Embryonal Pathology. PMID- 17860099 TI - II. On the Treatment of Vesico-Vaginal Fistula by Operation from within the Bladder. PMID- 17860100 TI - III. Uro-Genital Tuberculosis in the Male. PMID- 17860101 TI - IV. Thyroid Abscess; Thyroidectomy; Recovery. PMID- 17860102 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, May 23, 1894. PMID- 17860103 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, June 4, 1894. PMID- 17860105 TI - II. Thorburn on the Surgery of the Spinal Cord and Its Appendages. PMID- 17860104 TI - I. Lanz on the Thyreoid Question. PMID- 17860106 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860108 TI - II. Experimental Researches upon the Products of the Tubercle Bacillus. PMID- 17860107 TI - I. The Results of Operations for the Cure of Cancer of the Breast Performed at the Johns Hopkins Hospital from June, 1889, to January, 1894. PMID- 17860109 TI - III. The Operative Treatment of Gall-Stones Impacted in the Cystic or Common Bile Ducts. PMID- 17860110 TI - I. Operations at the Zurich Clinic for the Removal of Foreign Bodies from the OEsophagus. PMID- 17860111 TI - II. Bruns on the Results of Conservative Treatment of Tuberculous Coxitis. PMID- 17860112 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860113 TI - I. Operative Procedures in Congenital and Traumatic Dislocations of the Hip in Children. PMID- 17860114 TI - II. Resection of the Ileo-Caecal Coil of the Intestine; Its Indications, Results, and Modus Operandi, with a Review of 102 reported Cases and two heretofore Unpublished. PMID- 17860115 TI - III. Ether Anaesthesia; Clinical Notes on 300 Cases. PMID- 17860116 TI - IV. Extra-Uterine Pregnancy and Pelvic Haemorrhage; Cases and Remarks. PMID- 17860118 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 10, 1894. PMID- 17860117 TI - V. A Case of Horseshoe Kidney. PMID- 17860119 TI - I. Hoffa on the Pathological Anatomy of Scoliosis. PMID- 17860120 TI - I. On Some Points in the Technique of Resection of the Rectum. PMID- 17860121 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860122 TI - III. Thrombosis of the Mesenteric Veins as a Cause of Death after Splenectomy. PMID- 17860123 TI - IV. Case of Extraperitoneal Uretero-Lithotomy, following Nephro-Lithotomy and Nephrectomy. PMID- 17860124 TI - V. Clinical Report.-I. Complete Section of the Vas Deferens, End-to-End Union; II. Acute Suppuration of Knee-Joint: Open Treatment; III. Gastro-Enterostomy by the Murphy Button: Anastomoses by this Method. PMID- 17860126 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 14, 1894. PMID- 17860125 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 24, 1894. PMID- 17860127 TI - PROCEEDINGS OF THE SURGICAL SECTION OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, October 12, 1894. PMID- 17860128 TI - Guy de Chauliac and Henri de Mondeville,-A Surgical Retrospect. PMID- 17860129 TI - II. The Operative Relief of Gangrene of Intestine Due to Occlusion of the Mesenteric Vessels. PMID- 17860130 TI - I. On Movable Kidney. PMID- 17860131 TI - II. Peritonitis in the Male as a Complication of Gonorrhoea. PMID- 17860132 TI - III. Report of a Case of Stab-Wound of the Pericardium, Terminating in Recovery after Resection of a Rib and Suture of the Pericardium. PMID- 17860133 TI - IV. Complete Rectal Prolapse treated by Ventro-Fixation of the Rectum. PMID- 17860134 TI - V. Report of a Case of Pathological Separation of the Lower Epiphysis of the Femur. PMID- 17860135 TI - VI. The Relative Value of the Murphy Button and Absorbable Plates in Intestinal Anastomosis. PMID- 17860137 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, October 1, 1894. PMID- 17860136 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 28, 1894. PMID- 17860138 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, November 5, 1894. PMID- 17860139 TI - The Ambulant Treatment of Fractures of the Lower Extremity. PMID- 17860140 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860141 TI - I. The Surgical Treatment of Spina Bifida. PMID- 17860142 TI - II. The Treatment of Cicatricial Stricture of the OEsophagus by Retrograde Dilatation. PMID- 17860144 TI - IV. Suggestions for a Portable Instrument-Bag; Operating Overalls; a Bandage for Suprapubic Dressings; a Blanket for Protection of Patients during Operations; a Table for the Trendelenburg Posture; the Sterilization of Sponges; an Antiseptic Soap Paste. PMID- 17860143 TI - III. The Treatment of Injuries of the Spine and Cord by Sayre's Plaster-of-Paris Jacket. PMID- 17860145 TI - V. Report of a Case of Intracranial Trifacial Neurectomy. PMID- 17860146 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, December 12, 1894. PMID- 17860147 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, December 26, 1894. PMID- 17860148 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, December 3, 1894. PMID- 17860149 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, January 7, 1895. PMID- 17860150 TI - I. Burger on the Symptomatology and Diagnosis of Empyema of the Antrum of Highmore. PMID- 17860151 TI - II. Schede on the Non-Operative Treatment of Congenital Dislocations of the Hip. PMID- 17860152 TI - III. Castration for Prostatic Hypertrophy. PMID- 17860153 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860154 TI - I. The Parietal Incision in Abdominal Surgery. PMID- 17860155 TI - II. The Operative Treatment of Hernia, with a Report of Two Hundred Cases. PMID- 17860156 TI - III. A Study of Thirty-nine Cases of Strangulated Hernia. PMID- 17860157 TI - IV. A Preliminary Note on a New Method of Correcting Inveterate Talipes Varus by the Artificial Production of Pott's Fracture Deformity. PMID- 17860159 TI - VI. A New Method of Examination and Treatment of Diseases of the Rectum and Sigmoid Flexure. PMID- 17860158 TI - V. Hernia in the Linea Alba. PMID- 17860160 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 9, 1895. PMID- 17860161 TI - Effects of Unilateral Castration on the Prostate. PMID- 17860162 TI - I. The Surgical Treatment of Torticollis, with Especial Reference to the Spinal Accessory Nerve. PMID- 17860164 TI - III. Cases of Fracture of Spine and Laminectomy Treated in the Royal Infirmary, Newcastle-on-Tyne. PMID- 17860163 TI - II. Report of Additional Cases of Intracranial Neurectomy. PMID- 17860165 TI - IV. The Deciduoma Malignum. PMID- 17860166 TI - V. Two Cases of Gastrostomy for Cicatricial Stenosis of the OEsophagus. PMID- 17860167 TI - VI. On the Radical Cure of Inguinal and Femoral Hernia by Operation. PMID- 17860168 TI - VII. Fibrosis of Thyroid, Partial Thyroidectomy, Tracheotomy, and Dilatation of the Stenosed Trachea. PMID- 17860169 TI - VIII. Report of Four Cases of Nephrectomy for Pyo- and Pyelo-Nephritis. PMID- 17860170 TI - IX. A Case of Cholecystenterostomy Performed with Murphy's Button; Death from Haemorrhage on Fourth Day. PMID- 17860171 TI - X. A Surgical Crutch with Adjustable Leg-rests. PMID- 17860172 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 23, 1895. PMID- 17860173 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, February 13, 1895. PMID- 17860174 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860175 TI - The Gross Prize. PMID- 17860176 TI - I. A New Operative Method in the Treatment of Fracture of the Patella. PMID- 17860177 TI - II. Wounds of the Bladder in Operations for Hernia. PMID- 17860178 TI - III. A Report of Thirty-five Cases of Amputation of Omentum in Hernia Operations. PMID- 17860179 TI - IV. Restoration of the Lower Lip after the Method of Regnier. PMID- 17860180 TI - V. I. Case of Inguino-Labial Hernia; Ovary, Fallopian Tube, and Cornu of Uterus in Sac. II. Case of Hydronephrosis, of Thirty Years' Duration, with Calcification of the Inner Portion of the Wall of the Cyst. PMID- 17860182 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, February 4, 1895. PMID- 17860181 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, February 27, 1895. PMID- 17860183 TI - Lorenz on the Bloody Reposition of Congenital Hip-joint Dislocation. PMID- 17860184 TI - I. The Results of Double Castration in Hypertrophy of the Prostate. PMID- 17860185 TI - V. The Treatment of Tubercular Abscess. PMID- 17860186 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, March 4, 1895. PMID- 17860188 TI - Boeckel on Resection of the Knee without Drainage. PMID- 17860189 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860187 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, January 11, 1895. PMID- 17860190 TI - II. The Treatment of Spina Bifida by Plastic Operation. PMID- 17860191 TI - III. Immediate Suture of the Gall-Ducts and the Gall-Bladder after Extraction of Stones, with Cases. PMID- 17860192 TI - IV. The Radical Cure of Varicocele. PMID- 17860193 TI - I. The Results of Division or Resection in the Neck of the Pneumogastric and Phrenic Nerves. PMID- 17860195 TI - III. On Gall-Stones. PMID- 17860194 TI - II. The Treatment of Obstruction of the Common Gall-Duct. PMID- 17860196 TI - IV. The Relative Value of Operative and Hygienic Measures in the Treatment of Tuberculosis and Neoplasms of the Bladder. PMID- 17860197 TI - V. A Contribution to the Surgery of the Hypertrophied Prostate. PMID- 17860198 TI - VI. The Treatment of Postural Deformities of the Trunk by Means of Rapid and Thorough Physical Development. PMID- 17860199 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 13, 1895. PMID- 17860200 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 10, 1895. PMID- 17860201 TI - On the Cause of Death after Burns. PMID- 17860202 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860203 TI - I. The Surgical Treatment of Certain Forms of Bronchocele, with Reports of Sixteen Cases. PMID- 17860205 TI - III. Neural Infixation. PMID- 17860204 TI - II. The "Subgluteal" Triangle and its Surgical Importance. PMID- 17860206 TI - IV. Floating Bodies in Joints. PMID- 17860208 TI - VI. Chancre of the Tongue, with a Report of Four Cases. PMID- 17860207 TI - V. The Navel Loop. PMID- 17860209 TI - VII. Statistical Report of Seven Hundred and Three Major Amputations, from the Records of Eight Hospitals of New York City. PMID- 17860210 TI - VIII. A Successful Case of Transperitoneal Uretero-Lithotomy. PMID- 17860211 TI - IX. A Case of Hepato-Nephro-Lithotomy. PMID- 17860212 TI - X. A Case of Varicose Aneurism (Sacculated Arterio-Venous Fistule) of the Thigh treated by Transperitoneal Ligation of the External Iliac Artery. with Remarks of the Nomenclature of Vascular Lesions characterized by Pulsation. PMID- 17860213 TI - XI. A Case of Multiple Gunshot Wounds of the Intestine; Resection of Forty-three Inches of Ileum; Anastomosis with Murphy Button; Recovery. PMID- 17860214 TI - XII. A New Ward Surgical Dressing Carriage. PMID- 17860216 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, March 8, 1895. PMID- 17860215 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 24, 1895. PMID- 17860217 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860218 TI - I. The Etiology, Diagnosis, and Treatment of Malignant Disease. PMID- 17860219 TI - II. Operative Treatment of Cancer of Lips, Tongue, Floor of Mouth, and Pharynx. PMID- 17860220 TI - III. Treatment of Cancer of the Breast. PMID- 17860221 TI - IV. Operative Treatment of Cancer in the Female Generative Organs, Including the Uterus and Vulva. PMID- 17860222 TI - V. Operative Treatment of Cancer of the Male Genitals. PMID- 17860224 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, May 8, 1895. PMID- 17860223 TI - VI. The Modern Operative Treatment of Cancer of the Rectum. PMID- 17860226 TI - Bauby on the Treatment of Surgical Tuberculosis with Hot Water. PMID- 17860225 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, May 22, 1895. PMID- 17860227 TI - The Aseptic Treatment of Abscesses and Suppurating Wounds. PMID- 17860229 TI - II. The Location and Removal of Missiles from the Cranial Cavity. PMID- 17860228 TI - I. Operative Treatment of Aneurisms of the Third Portion of the Subclavian Artery. PMID- 17860230 TI - III. Post-Typhoid Bone Lesions. PMID- 17860232 TI - V. Report of a Case of Impacted Urethral Calculus. PMID- 17860231 TI - IV. An Improvement in the Technique of Catheterization of the Ureter in the Female. PMID- 17860233 TI - VI. The Operative Treatment of Fracture of the Patella. PMID- 17860234 TI - VII. Three Cases of Wiring of the Patella for Old Fracture, with Division of the Quadriceps Muscle, and Chiselling Loose the Tubercle of the Tibia in Two of the Cases. PMID- 17860235 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, April 12, 1895. PMID- 17860236 TI - Intestinal Anastomosis,-Maunsell's Method of Suture. PMID- 17860237 TI - I. Operative Treatment of Epispadias by Transplantation of the Urethra. PMID- 17860238 TI - II. Treatment of Epithelioma of the Ala of the Nose. PMID- 17860239 TI - III. Intraperitoneal Rupture of the Bladder. PMID- 17860240 TI - IV. Contribution to the Study of Nephrolithiasis. PMID- 17860241 TI - V. Some Considerations in the Operative Treatment of Fracture of the Patella, with Special Reference to Suture Material and the Use of Salt Solution. PMID- 17860242 TI - VI. A Further Case of Removal of the Upper Extremity together with the Scapula and Clavicle. PMID- 17860243 TI - VII. Operative Treatment of Aneurisms of the Third Portion of the Subclavian Artery. PMID- 17860245 TI - IX. Case of Intra-Uterine Fracture of the Tibia resulting in Congenital Ankle Deformity. PMID- 17860244 TI - VIII. Large Cyst of the Pancreas treated by Lateral Incision and Drainage; Recovery. PMID- 17860246 TI - X. A Case of Congenital Subspinous "Dislocation" of the Head of the Humerus. PMID- 17860247 TI - XI. Unilateral Laryngectomy for Cancer; no Recurrence after Three Years. PMID- 17860248 TI - XII. Two Cases of Bone-Grafting for Cranial Defect. PMID- 17860249 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 9, 1895. PMID- 17860250 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, May 10, 1895. PMID- 17860251 TI - Graser on the Adhesions of Serous Membranes. PMID- 17860253 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860252 TI - I. On the Value of Cocainization of the Nasal Mucous Membrane before and during Surgical Anaesthesia, with Report of One Hundred Cases. PMID- 17860254 TI - II. On the Treatment of the Sac in Operations for the Radical Cure of Hernia. PMID- 17860255 TI - III. An Improved Clamp for Facilitating Lateral Anastomosis of Intestine. PMID- 17860256 TI - IV. Congenital Absence of Radii, with Operation. PMID- 17860257 TI - V. Stretching of the Lingual Branch of the Fifth Nerve for the Relief of Neuralgia of the Tongue. PMID- 17860258 TI - VI. Enterorrhaphy with Murphy's Button for Gunshot Perforation of Intestine; Recovery. PMID- 17860259 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 23, 1895. PMID- 17860260 TI - Doyen on Extirpation of the Gasserian Ganglion. PMID- 17860261 TI - Ribbert on the Origin of Tumors. PMID- 17860262 TI - I. Comparative Frequency of Stone in the Bladder in the White and Negro Races. PMID- 17860263 TI - II. Two Cases of Intraperitoneal Suprapubic Cystotomy for Stone. PMID- 17860264 TI - III. Chronic Perivesical Inflammation. PMID- 17860265 TI - IV. Injuries to Nerves in Fractures: Report of Two Operative Cases in Fractures of the Humerus and Clavicle. PMID- 17860266 TI - V. Report of Two Successful Hip-Joint Amputations, the Second of which was Performed by a New Method. PMID- 17860267 TI - VI. A Contribution to the Theory of Cerebral Concussion. PMID- 17860268 TI - VII. An Improved Apparatus for Drainage by Siphonage in Operations on the Bladder, Chest, andother Cavities. PMID- 17860269 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 13, 1895. PMID- 17860271 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, October 11, 1895. PMID- 17860270 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 27, 1895. PMID- 17860272 TI - Myomata of the Bladder. PMID- 17860273 TI - Von Bungner on the Healing in of Foreign Bodies under the Influence of Chemical and Microparasitic Irritation. PMID- 17860274 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860276 TI - I. The Diagnosis and Treatment of Surgical Renal Disease. PMID- 17860275 TI - Two Additional Cases of Aneurism of the Third Portion of the Right Subclavian Artery. PMID- 17860277 TI - II. Relief of Tympanites by Posture. PMID- 17860278 TI - III. Note on Drainage through the Rectum of Pelvic Abscesses due to Appendicitis. PMID- 17860279 TI - IV. Note on the Post-Operative Treatment of Wry-Neck. PMID- 17860280 TI - V. Case of Sternal Dislocation of Second and Third Costal Cartilages and of Clavicle, with Fracture of Fourth and Fifth Cartilages. PMID- 17860281 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, December 11, 1895. PMID- 17860282 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 8, 1896. PMID- 17860284 TI - Gluck on Osteoplasty. PMID- 17860283 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, November 8, 1895. PMID- 17860286 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860285 TI - Von Bergmann on some Advances in Brain Surgery. PMID- 17860287 TI - I. The Relation of the Weather to Fatality following Surgical Operations. PMID- 17860289 TI - III. Subperitoneal Tissue. PMID- 17860288 TI - II. A New Operation for Hypospadias. PMID- 17860290 TI - IV. Case of Gastrotomy for Foreign Body impacted in OEsophagus. PMID- 17860291 TI - V. Gunshot Wound of the Intestines, with Sixteen Perforations; Enterorrhaphy; Use of the Murphy Button; Recovery. PMID- 17860292 TI - VI. Note on the Treatment of Diffuse Osteomyelitis of the Femur by Demedullization. PMID- 17860294 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 22, 1896. PMID- 17860293 TI - VII. Case of a Fibro-Angioma situated beneath the Four-Headed Extensor of the Leg; with some account of Similar Muscular Tumors. PMID- 17860295 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, December 13, 1895. PMID- 17860296 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, October 7, 1895. PMID- 17860297 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, November 4, 1895. PMID- 17860298 TI - A Simple and Reliable Means of Bladder-Drainage. PMID- 17860299 TI - I. The Reduction of Dislocation of the Humerus complicated by Fracture at the Anatomical Neck; Operative Treatment of Separation of the Lower Epiphysis of the Femur. PMID- 17860300 TI - II. On Acute Primary Osteomyelitis of the Vertebrae. PMID- 17860302 TI - IV. An Intracranial Implantation Dermoid Tumor. PMID- 17860301 TI - III. Research on the Surgical Anatomy of the Middle Meningeal Artery. PMID- 17860303 TI - V. Case of Operative Injury to the Thoracic Duct at the Root of the Neck. PMID- 17860305 TI - VII. A Bullet-Probe and Bullet-Forceps New in Principle. PMID- 17860304 TI - VI. A Case of Sarcoma of the Tongue. PMID- 17860307 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, February 12, 1896. PMID- 17860306 TI - VIII. Laparotomy for Perforating Typhoid Ulcer of the Ileum: Death on the Fourth Day from Obstruction of the Hepatic Flexure of the Colon by an Old Adhesion Band. PMID- 17860308 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, February 26, 1896. PMID- 17860309 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, January 10, 1896. PMID- 17860310 TI - I. Conservative Operative Treatment of Sacculated Kidney-Cystonephrosis. PMID- 17860311 TI - II. Treatment of Intraperitoneal Rupture of the Urinary Bladder. PMID- 17860312 TI - III. Results of Castration upon Prostatic Hypertrophy as shown in Six Cases. PMID- 17860313 TI - IV. Further Experience in the Effect of the Simultaneous Ligation of both Internal Iliac Arteries for Hypertrophy of the Prostate Gland. PMID- 17860314 TI - V. Results and Methods of Surgical Operations at the New York Hospital from August 1, 1895, to January 31, 1896, and at the House of Relief from August 1, 1895, to March 10, 1896. PMID- 17860315 TI - VI. The Operative Treatment of Ulcer of the Stomach, with Report of a Recent Successful Case. PMID- 17860316 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 11, 1896. PMID- 17860317 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, February 14, 1896. PMID- 17860318 TI - Should the Appendix be Removed in every Case of Appendicular Abscess. PMID- 17860319 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860320 TI - I. On the Anatomy of the Anus. PMID- 17860321 TI - II. Further Considerations on the Anatomy of Oblique Inguinal Hernia. PMID- 17860322 TI - III. The Treatment of Intracapsular Fracture of the Femur. PMID- 17860323 TI - IV. The Ligature in Oophorectomy. PMID- 17860324 TI - V. Fracture of the Os Calcis, with Report of a Case of Comminuted Fracture with an Unique Method of Treatment. PMID- 17860326 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 25, 1896. PMID- 17860325 TI - VI. Report of a Case of Sarcoma of the Caecum. PMID- 17860328 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, February 3, 1896. PMID- 17860327 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, January 6, 1896. PMID- 17860330 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860329 TI - The Ambulatory Treatment of Fractures of the Lower Extremity. PMID- 17860331 TI - I. Some Observations Relative to the Surgery of the Large Intestine. PMID- 17860332 TI - II. The Operative Treatment of Jacksonian and Focal Epilepsy. PMID- 17860333 TI - III. A Theory of the Ultimate Etiology of Deformity and its Practical Application. PMID- 17860334 TI - IV. The Treatment of Traumatic Lesions of the Kidney, with Tables of 155 Cases. PMID- 17860336 TI - VI. Large Parosteal Fibro-Sarcoma of the Thigh. PMID- 17860335 TI - V. Case of Interscapulo-Thoracic Amputation for Injury. PMID- 17860338 TI - VIII. Remarks on some Cases of Deformity of the External Ear. PMID- 17860337 TI - VII. Extraperitoneal Exploration of the Ureter followed by Nephrolithotomy. PMID- 17860339 TI - IX. Cleft Hand: A Report of a Case Successfully Treated by the Use of Periosteal Flaps. PMID- 17860340 TI - X. Case of Bullet Embedded in the Tissues of the Neck, Located by Skiagraphy. PMID- 17860341 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 8, 1896. PMID- 17860342 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, April 10, 1896. PMID- 17860344 TI - II. Rydygier on the Treatment of Intestinal Intussusception. PMID- 17860343 TI - I. The Use of Skiagraphy for the Detection and Location of Foreign Bodies Impacted in the OEsophagus. PMID- 17860345 TI - I. The Question of the Origin of Malignant from Non-Malignant Uterine Neoplasms. PMID- 17860346 TI - II. The Question of Castration for Enlarged Prostate. PMID- 17860347 TI - III. Report of a Case of Gastrotomy for Removal of a Pedunculated Carcinoma of the Stomach. PMID- 17860348 TI - IV. An Experimental Study of the Pathological Anatomy and Bacteriology of Salpingo-Ovaritis. PMID- 17860349 TI - V. Contribution to the Statistics of Foreign Bodies in the Peritoneal Cavity. PMID- 17860350 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 22, 1896. PMID- 17860351 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, May 8, 1896. PMID- 17860352 TI - I. The Question of Castration for Enlarged Prostate. PMID- 17860354 TI - II. An Experimental Study of the Pathological Anatomy and Bacteriology of Salpingo-Ovaritis. PMID- 17860353 TI - I. Operative Treatment of Anchylosis of the Shoulder-Joint. PMID- 17860355 TI - III. The Technique of Temporary Resection of the Skull, with Demonstration of a New Set of Instruments. PMID- 17860356 TI - IV. Ambulatory Treatment of Fractures in Children. PMID- 17860357 TI - V. Case of Pelvic Tumor formed by a Calcified Meckel's Diverticulum uniting the Ileum and Bladder. PMID- 17860358 TI - VI. Intestinal Fistula following Appendicitis. PMID- 17860360 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, May 27, 1896. PMID- 17860359 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, May 13, 1896. PMID- 17860361 TI - I. Felix Wurtz and Pierre Franco,-A Glimpse of Sixteenth Century Surgery. PMID- 17860362 TI - I. The Surgery of Intrathoracic Tuberculosis. PMID- 17860363 TI - II. Intracranial Operations for the Cure of Facial Neuralgia. PMID- 17860364 TI - III. The Treatment of some Traumatic Lesions of the Knee-Joint. PMID- 17860365 TI - IV. An Improved Surgical Bed. PMID- 17860366 TI - V. Extirpation of the Rectum per Vaginam, with Utilization of the Vagina to replace the lost Rectal Tissue. PMID- 17860367 TI - VI. The Remote Effects of Excision of the Fibula. PMID- 17860368 TI - VII. Report of a Case of Cholecystostomy with Subsequent Cholecystenterostomy for Biliary Obstruction in a Patient Eighty Years of Age. PMID- 17860369 TI - Remarks on the Surgery of Perforating Gastric Ulcer. PMID- 17860370 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860371 TI - I. Tuberculosis of the Superficial Lymphatic Glands. PMID- 17860372 TI - II. Remarks upon Carcinoma of the Tongue, with Special Reference to Kocher's Method of its Removal. PMID- 17860373 TI - III. Message and Movements in the Treatment of Fractures. PMID- 17860374 TI - IV. Fixation of the Round Ligaments in Alexander's Operation. PMID- 17860375 TI - V. Amputation of the Foot with a Dorsal Flap. PMID- 17860376 TI - VI. What Causes the Pain in Certain Cases of Chronic Appendicitis? PMID- 17860377 TI - VII. Two Cases of Perforating Gunshot Wound of the Kidney. PMID- 17860378 TI - VIII. A Case of Permanent Faecal Fistula of the Small Intestine following Operation for Appendical Abscess. PMID- 17860379 TI - IX. Report of a Case of Chronic Intussusception caused by an Adenoma of the Ileum relieved by Intestinal Resection. PMID- 17860380 TI - X. Intracranial Operations for the Cure of Facial Neuralgia. (Concluded.). PMID- 17860381 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, June 1, 1896. PMID- 17860382 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860383 TI - I. The Diagnosis and Treatment of Surgical Affections of the Kidneys, with Illustrative Cases. PMID- 17860384 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 28, 1896. PMID- 17860385 TI - I. Questions involved in the Practice of Castration for Enlarged Prostate. PMID- 17860386 TI - II. Reichel on the After-Treatment in Cases of Abdominal Section. PMID- 17860387 TI - Questions involved in the Practice of Castration for Enlarged Prostate. PMID- 17860388 TI - II. From the Surgical Section of the Twelfth International Medical Congress in Moscow. PMID- 17860389 TI - II. Laminectomy for Simple Fractures, with a Report of Three Cases. PMID- 17860390 TI - III. The Effects of Small Calibre Bullets as used in Military Arms. PMID- 17860391 TI - IV. Uretero-Ureteral Anastomosis. PMID- 17860392 TI - V. Contribution to the History of Operative Interference for the Relief of Obstruction of the Common Choledoch Duct by Biliary Calculi. PMID- 17860394 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 14, 1896. PMID- 17860393 TI - VI. A Further Case of Primary Tuberculosis of the Breast. PMID- 17860395 TI - I. Report of Sixty-nine Cases of Amputation at the Hip-Joint by the Author's Method. PMID- 17860396 TI - II. Air-Distention of the Bladder in Suprapubic Cystotomy. PMID- 17860397 TI - III. Actinomycosis. PMID- 17860399 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 25, 1896. PMID- 17860398 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 11, 1896. PMID- 17860400 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, October 9, 1896. PMID- 17860401 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, November 13, 1896. PMID- 17860402 TI - Krumm on Narcosis Paralysis. PMID- 17860403 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860404 TI - An Improvement in the Technique of End-to-End Intestinal Anastomosis. PMID- 17860406 TI - II. The Radical Cure of Hernia, with a Report of Three Hundred and Sixty Cases. PMID- 17860405 TI - I. The Surgical Treatment of Perforating Typhoid Ulcer. PMID- 17860407 TI - III. Tertiary Syphilitic Epididymitis. PMID- 17860408 TI - IV. Orthopaedic Operations at the Hospital for the Ruptured and Crippled, from October 1, 1895, to October 1, 1896. PMID- 17860409 TI - V. Observations upon the Absorption of Fluids by the Peritoneum. PMID- 17860410 TI - VI. Contribution to the Surgery of the Large Intestine. PMID- 17860412 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, December 9, 1896. PMID- 17860411 TI - VII. Cases of Rupture of the Quadriceps Extensor Tendon treated by Suture. PMID- 17860414 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860413 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, December 23, 1896. PMID- 17860415 TI - Castration for Enlargement of the Prostate. PMID- 17860417 TI - II. The Effect of High Altitudes in Aggravating Surgical Shock. PMID- 17860416 TI - I. The Operative Treatment of Cancer of the Rectum. PMID- 17860419 TI - IV. Contribution to Traumatic Abdominal Surgery: I. Report of a Case of Contusion and Subsequent Gangrene of a Portion of the Ileum, Complicated by Laceration of a Horseshoe Kidney. II. Report of a Case of Gangrenous Strangulated Hernia. PMID- 17860418 TI - III. The Operative Treatment of Hallux Valgus. PMID- 17860420 TI - V. Some Fractures of the Lower End of the Radius as seen by the Rontgen Rays. PMID- 17860422 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, December 11, 1896. PMID- 17860421 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 13, 1897. PMID- 17860423 TI - I. Schlatter on the Treatment of Traumatic Injuries of the Liver. PMID- 17860425 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860424 TI - II. Bruns on the Evolution of the Modern Treatment of Goitre. PMID- 17860427 TI - The Treatment of Varicose Veins. PMID- 17860426 TI - Disappearing Tumor of the Abdomen. PMID- 17860428 TI - I. Certain Intermittent Cysts of the Ovary and Kidney. PMID- 17860429 TI - II. Clinical Contribution to the Surgery of the Liver. PMID- 17860430 TI - III. An Analysis of Two Hundred and Twenty-One Cases of Foreign Body introduced into the Male Bladder per Urethram, with Report of a Recent Case. PMID- 17860431 TI - IV. Tracheotomy as Preliminary to Operations upon the Upper Air-Passages. PMID- 17860432 TI - V. Direct Intra-Abdominal Finger-Compression of the Common Iliac Artery during Amputation at the Hip-Joint. PMID- 17860433 TI - VI. Upon the Deportment of Needles Penetrating the Tissues. PMID- 17860434 TI - VII. Contribution to the Surgery of the Carotid Arteries. PMID- 17860435 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, February 10, 1897. PMID- 17860437 TI - Wolfler on the Surgery of the Stomach and Intestines. PMID- 17860436 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, January 8, 1897. PMID- 17860438 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860439 TI - I. Further Observations on Fracture of the Neck of the Femur in Childhood, with Especial Reference to its Diagnosis and to its more Remote Results. PMID- 17860440 TI - II. The Treatment of General Septic Peritonitis. PMID- 17860441 TI - III. Open Measures in the Treatment of so-called Simple and Compound Fractures. PMID- 17860443 TI - V. A Case of Persistent Thyro-Glossal Duct or of Congenital Laryngeal Diverticulum successfully treated by Excision. PMID- 17860442 TI - IV. Cases of Abdominal Cystic Tumor in the Male. PMID- 17860445 TI - VII. Removal of a Thyroid Sarcoma under Cocaine Anaesthesia. PMID- 17860444 TI - VI. Double Fracture of the Clavicle from Direct Violence. PMID- 17860446 TI - VIII. Cases of Radical Cure of Psoas Abscess by Operation. PMID- 17860447 TI - IX. Report of a Case of Cavernous Angioma of the Spleen. PMID- 17860448 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, February 24, 1897. PMID- 17860450 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, October 5, 1896. PMID- 17860449 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, February 12, 1897. PMID- 17860451 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, December 7, 1896. PMID- 17860453 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860452 TI - The Relations Existing between Granulation Tissue of Repair, the Infective Granulomata, and the Sarcomata. PMID- 17860454 TI - A Case of Central Narcosis Paralysis. PMID- 17860455 TI - I. Mesenteric Cysts. PMID- 17860456 TI - VI. The Galvano-Cautery in the Surgery of the Tonsil. PMID- 17860457 TI - VII. Report of a Case of Sarcoma of the Tonsil, Removed by Lateral Pharyngotomy. PMID- 17860458 TI - VIII. Gall-Stones formed around Silk Sutures Twenty Months after Recovery from Cholecystotomy. PMID- 17860459 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 10, 1897. PMID- 17860460 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, March 12, 1897. PMID- 17860461 TI - Wolff on the Functional Pathogenesis of Deformities. PMID- 17860462 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860463 TI - II. The Place of the Murphy Button in Gastro-Enterostomy. PMID- 17860464 TI - III. Solid Mesenteric Tumors, with Report of Case. PMID- 17860465 TI - IV. Surgical Treatment of Tumor of the Liver, with the Report of a Case. PMID- 17860466 TI - V. The Advantages of the Trendelenburg Posture during all Operations involving directly or indirectly the Cavities of the Mouth, Nose, and the Trachea, with a Report of Two Cases of Epithelioma and Sarcoma of the Tonsil. PMID- 17860467 TI - I. Tenoplastic Surgery. PMID- 17860468 TI - II. Colopexy for the Relief of Prolapsus of the Rectum. PMID- 17860469 TI - III. Strangulation of the Intestine by Meckel's Diverticulum. PMID- 17860471 TI - V. Remarks on Laminectomy, with Report of a Case done Sixteen Months after Fracture. PMID- 17860470 TI - IV. Successful Treatment of Sarcoma by Electrolysis and Cataphoresis, combined with the Internal Use of Donovan's Solution. PMID- 17860472 TI - VI. A Case of Perforating Typhoid Ulcer, with Recovery, after Operation. PMID- 17860474 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 24, 1897. PMID- 17860473 TI - VII. The Late Results of a Case of Implantation of Bone-Chips in a Cyst of the Head of the Tibia. PMID- 17860475 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 14, 1897. PMID- 17860476 TI - Clark on Drainage of the Peritoneal Cavity. PMID- 17860478 TI - A Case of Obstruction of Cystic Duct accompanied by Icterus. PMID- 17860477 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860479 TI - I. A Plea for a Revised Nomenclature of Operations upon the Alimentary Canal. PMID- 17860481 TI - III. The Technique of Intracranial Surgery. PMID- 17860480 TI - II. A Preliminary Comparison of Methods and Results in Operative Surgery at the Sea Level (New York) and in Places of High Altitude (Denver). PMID- 17860482 TI - IV. A Contribution to the Experimental Surgery of the Ureter. PMID- 17860484 TI - VI. Report upon the Use of a Mixture of Castor Oil and Balsam of Peru as a Surgical Dressing. PMID- 17860483 TI - V. Incision of the Kidney in Cases of Uncomplicated Nephrolithiasis. PMID- 17860485 TI - VII. A Report of Two Cases of Ante-Operative Asphyxia, following Acute Intestinal Obstruction. PMID- 17860486 TI - VIII. Some Remarks on Hospital Beds, with a Description of a New Model. PMID- 17860487 TI - IX. A Case of Diaphragmatic Hernia. PMID- 17860488 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 28, 1897. PMID- 17860489 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, May 12, 1897. PMID- 17860490 TI - Kraske on Cancer of the Rectum. PMID- 17860491 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860492 TI - I. On the Lower Limitations of the Pleural Cavities with Regard to Certain Surgical Operations. PMID- 17860494 TI - III. Spontaneous Dislocation of the Hip-Joint occurring during the Course of the Acute Infectious Diseases. PMID- 17860493 TI - II. Contribution to the Surgery of Hepatic Abscess. PMID- 17860495 TI - IV. The so-called Hot-Air Treatment of Painful and Partially Ankylosed Joints, and an Experimental Investigation of the Physiological Effect of the Local Application of Hot Air on General Metabolism. PMID- 17860497 TI - VI. Ligature of the Innominate Artery for Haemorrhage, with the Report of a Case. PMID- 17860496 TI - V. Some Practical Points upon Fracture of the Thigh-Bone, especially in Babies. PMID- 17860498 TI - VII. Primary Sarcoma of the Thyroid Gland. PMID- 17860500 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, May 26, 1897. PMID- 17860499 TI - VIII. Very Large Myxolipoma of Leg, Thigh, and Knee-Joint; Amputation at Hip Joint. Recovery. PMID- 17860501 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860502 TI - Cysts of the Mesentery. PMID- 17860503 TI - I. Sarcoma of the Kidney in Children: A Critical Review of the Pathology, Symptomatology, Prognosis, and Operative Treatment as seen in One Hundred and Forty-five Cases. PMID- 17860504 TI - II. A New Method for the Radical Cure of Inguinal Hernia: Intraperitoneal Transplacement of the Spermatic Cord and Typical Obliteration of the Internal Ring and Inguinal Canal. PMID- 17860505 TI - III. A New Incision for the Removal of the Appendix Vermiformis. PMID- 17860506 TI - IV. A Case of Actinomycosis Hominis, involving the Tissues of the Back and the Lungs: with Pathological Report. PMID- 17860507 TI - V. A Case of Vaginal Anus, the Result of a Hysterectomy, Cured by Ileocolostomy. PMID- 17860508 TI - VI. Report of a Case of Total Laryngectomy for Carcinoma. PMID- 17860510 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860509 TI - Kronlein on Carcinoma of the Pharynx and its Operative Treatment. PMID- 17860511 TI - I. The Treatment of Tetanus. PMID- 17860512 TI - II. Chronic Inflammation of the Spermatic Cord, with Haemorrhagic Infiltration and Gangrene of the Testis, following Thrombosis of the Vessels. PMID- 17860513 TI - III. The Role of the Cervical Fascia in producing Antero-Posterior Curvatures of the Spinal Column. PMID- 17860514 TI - IV. Case of Cystic Dilatation of the Common Bile-Duct in a Child. PMID- 17860515 TI - V. Report of Cases of Circular Resection, respectively of Pylorus, Caecum with Ascending Colon, and Sigmoid Flexure. PMID- 17860516 TI - VI. Some Practical Remarks upon the Use of X-Rays in Surgery, with Skiagraph of a Dislocation of the Astragalus Backward. PMID- 17860518 TI - The Geographical Distribution, Prophylaxis, and Therapeutics of Tetanus. PMID- 17860517 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 13, 1897. PMID- 17860519 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860520 TI - I. Some Considerations on Abdominal Incisions. PMID- 17860521 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, November 1, 1897. PMID- 17860523 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860522 TI - Terrier and Auvray on Floating Liver (Hepatoptosis) and its Surgical Treatment. PMID- 17860524 TI - Carotid Excision for Malignant Growths. PMID- 17860525 TI - II. The Remote Results after Operations for Renal Tuberculosis. PMID- 17860526 TI - III. Treatment of Acromio-Clavicular Dislocation. PMID- 17860527 TI - IV. Note on the Repair of Wounds of the Ureter. PMID- 17860528 TI - V. The Sterilization of Catgut by the Jefferson Method. PMID- 17860529 TI - VI. An Improved Technique for Avoidance of Fistula after Cholecystostomy. PMID- 17860530 TI - VII. Report of a Case of Traumatic Periencephalitis with Cerebral Abscess. PMID- 17860531 TI - VIII. Three Cases of Swallowed Foreign Bodies located by the Rontgen Rays. PMID- 17860532 TI - IX. Carcinoma of the Breast, with a Round-Celled Sarcoma in the Submaxillary Region in the same Individual. PMID- 17860533 TI - X. A combined Aspirating Needle and Director for opening Deep-Seated Abscesses. PMID- 17860534 TI - XI. A Preliminary Report upon the Examination of the Bladder and Catheterization of the Ureters in Men. PMID- 17860535 TI - XII. Four Cases of Secondary Syphilis complicated with Chronic Appendicitis, in which a continuous Course of Tonic Doses of Mercury resulted in Marked Subsidence of the Appendicular Symptoms. PMID- 17860536 TI - XIII. Remarks upon some Points in the Techique of the Operation for Appendicitis. PMID- 17860537 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 27, 1897. PMID- 17860538 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 10, 1897. PMID- 17860539 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, October 8, 1897. PMID- 17860540 TI - I. A Study of the Cases of Disease of the Female Generative Organs personally treated during Ten Years' Work in the Methodist Episcopal Hospital in Brooklyn. PMID- 17860541 TI - II. Extraperitoneal Rupture of the Bladder complicated by Fracture of the Pelvis Report of a Recent Cured Case, with a Study of Ninety Cases collected from Literature. PMID- 17860542 TI - III. Surgical Treatment of Acute Rheumatic Arthritis. PMID- 17860543 TI - IV. Branchial Carcinoma. PMID- 17860544 TI - V. Report of a Case of Epithelioma of the Skin of the Face, with Unusual Course of Infection of Lymph-Nodes. PMID- 17860545 TI - VI. A Case of Floating Gall-Bladder and Kidney complicated by Cholelithiasis, with Perforation of the Gall-Bladder. PMID- 17860546 TI - VII. Report of a Case of Choledochocystotomy. PMID- 17860547 TI - VIII. A Practical Gauze Bandage-Roller. PMID- 17860548 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, November 12, 1897. PMID- 17860550 TI - Why may Recurrent Carcinoma be Locally Worse than the Primary Disease of the same Region. PMID- 17860549 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, April 5, 1897. PMID- 17860552 TI - I. Contribution to the Surgery of the Sacral Region. PMID- 17860551 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860553 TI - II. The Influence of Injury upon the Development of Sarcoma. PMID- 17860554 TI - III. A Study of Twenty-nine Cases of Cancer of the Breast submitted to Operation. PMID- 17860555 TI - IV. Remarks upon the Differential Diagnosis, the Pathology, and the Treatment of Appendicitis. PMID- 17860556 TI - V. Value of Castration to Facilitate Detection of Stone in the Bladder, in the Presence of Prostatic Hypertrophy. PMID- 17860557 TI - VI. A Study of the Cases of Disease of the Female Generative Organs personally treated during Ten Years' Work in the Methodist Episcopal Hospital in Brooklyn. PMID- 17860558 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 24, 1897. PMID- 17860559 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, December 10, 1897. PMID- 17860560 TI - The Discussion of Contusions of the Abdomen at the Recent French Congress of Surgery. PMID- 17860561 TI - Priority of an Aspirator-Needle. PMID- 17860562 TI - I. Observations upon the Etiology of Tumors. PMID- 17860563 TI - II. Contribution to the Surgery of the Pelvis of the Kidney. PMID- 17860565 TI - IV. A Contribution to the Surgery of the Suprarenal Capsule, with Report of a Successful Case of its Removal. PMID- 17860564 TI - III. The Other Kidney in Contemplated Nephrectomy. PMID- 17860566 TI - V. Intestinal Obstruction caused by Meckel's Diverticulum. PMID- 17860568 TI - VII. Forcible Straightening of the Spine in Pott's Disease, with Report of Case. PMID- 17860567 TI - VI. A Modified Operation for the Radical Cure of Inguinal Hernia. PMID- 17860569 TI - VIII. Cystoscopy and Catheterization of the Ureters in the Male. PMID- 17860570 TI - IX. Large Multiple Neurofibromata of the Cervical Sympathetic. PMID- 17860571 TI - X. A Study of the Cases of Disease of the Female Generative Organs personally treated during Ten Years' Work in the Methodist Episcopal Hospital in Brooklyn. PMID- 17860572 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, December 8, 1897. PMID- 17860573 TI - Rieder on the Pathology and Treatment of Rectal Strictures. PMID- 17860574 TI - I. Further Observations regarding the Use of the Bone-Clamp in Ununited Fractures, Fractures with Malunion, and Recent Fractures, with a Tendency to Displacement. PMID- 17860576 TI - III. Operation without Ether or Chloroform Narcosis. General Observations and Report of Illustrative Cases. PMID- 17860575 TI - II. Remarks on the Treatment of Stone in the Bladder, when associated with Hypertrophy of the Prostate. PMID- 17860577 TI - IV. The Treatment of Fractures of the Lower Extremity. Clinical Report of Four Hundred and Fifty Cases treated in the Methodist Episcopal Hospital in the City of Brooklyn. PMID- 17860579 TI - VI. Varicose Veins and their Treatment by Trendelenburg's Operation. PMID- 17860578 TI - V. Contribution to the Study of Appendicitis Obliterans. PMID- 17860580 TI - VII. A Method for Partial Resection of the Eyeball and of the Optic Nerve. PMID- 17860581 TI - VIII. Case of Hydronephrosis from Stone impacted in the Ureter of a Child. PMID- 17860582 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, December 22, 1897. PMID- 17860583 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 12, 1898. PMID- 17860584 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, February 9, 1898. PMID- 17860585 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, December 6, 1897. PMID- 17860586 TI - Ultimate Results of Castration as a Means of Relief for Obstructive Hypertrophy of the Prostate. PMID- 17860587 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860588 TI - I. Remarks on Surgery of the Bile-Ducts. PMID- 17860589 TI - II. Operative Wounds of the Thoracic Duct. Report of a Case with Suture of the Duct. PMID- 17860590 TI - III. Successful Resection of the Ileo-Caecal Coil for Carcinoma. PMID- 17860592 TI - V. Total Excision of the Fibula for Sarcoma. PMID- 17860591 TI - IV. The Importance of Chronic Irritability of the Colon with Mucous Stools as a Symptom of Appendicitis. PMID- 17860593 TI - VI. A Case of Hara-Kiri which terminated in Recovery. PMID- 17860595 TI - VIII. A Surgical Wash-Stand. PMID- 17860594 TI - VII. Report of Six Cases of Hip-Joint Amputation. PMID- 17860596 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, February 23, 1898. PMID- 17860597 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, January 14, 1898. PMID- 17860598 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, February 7, 1898. PMID- 17860599 TI - Pathology and Operative Relief of Non-Malignant Pyloric Stenosis. PMID- 17860600 TI - I. A Case of Subclavian Aneurism treated by Excision of the Sac, with Remarks on the Ligation of the Innominate Artery and on the Treatment of Aneurism. PMID- 17860602 TI - V. Osteotomoclasis: A Preliminary Note on a Modified Operation to Correct Curved Tibia. PMID- 17860601 TI - IV. The Use of Rubber Gloves in Operative Surgery. PMID- 17860603 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 9, 1898. PMID- 17860604 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, February 11, 1898. PMID- 17860605 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, March 8, 1898. PMID- 17860606 TI - The Question of Priority in Choledocholithotomy. PMID- 17860607 TI - Rejoinder by Dr. Marcy. PMID- 17860608 TI - II. Curvature of the Neck of the Femur, sometimes called "Coxa Vara". PMID- 17860609 TI - III. The Question of Operative Interference in Recent, Simple Fractures of the Patella. PMID- 17860610 TI - I. The Surgical Occlusion of the Cerebral Sinuses. PMID- 17860612 TI - III. Gunshot Injuries of the Spine, with Report of a Case. PMID- 17860611 TI - II. Hysteria from a Surgical Stand-Point. PMID- 17860613 TI - IV. Treatment of Fracture of the Patella. PMID- 17860615 TI - VI. Two Cases of Recovery from Traumatic Tetanus after the Use of Antitoxin. PMID- 17860614 TI - V. Report of Two Cases of Injury to the Thoracic Duct in Operations on the Neck. PMID- 17860616 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 23, 1898. PMID- 17860618 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, April 8, 1898. PMID- 17860617 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 13, 1898. PMID- 17860620 TI - I. Metatarsalgia or Morton's Disease. PMID- 17860619 TI - Observations on Gastro-Enterostomy at the Breslau Clinic. PMID- 17860621 TI - II. The Cranial "Cracked-Pot" Sound as a Symptom of Cerebellar Tumors. PMID- 17860623 TI - IV. Enterorrhaphy without Buttons, Plates, or Rings. PMID- 17860622 TI - III. Report of a Case of Traumatic Rupture of Pancreas, with Formation of Haemorrhagic Cyst, and Pancreatic Fistula. PMID- 17860624 TI - V. A Means of Regulating Inflation of the Bladder preliminary to Suprapubic Cystotomy. PMID- 17860626 TI - VII. Report of a Case of Castration for Enlarged Prostate, without Benefit, followed one year later by Prostatectomy. PMID- 17860625 TI - VI. Four Atypical Cases of Appendicitis. PMID- 17860627 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 27, 1898. PMID- 17860628 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, May 2, 1898. PMID- 17860629 TI - Von Hacker on OEsophagoscopy and its Clinical Value. PMID- 17860631 TI - I. On the Cause and Mechanical Treatment of Subluxation of the Semilunar Cartilages of the Knee-Joint. PMID- 17860630 TI - Konig on Cystic Enchondrofibromata and Solitary Cysts of the Long Bones. PMID- 17860632 TI - II. A Contribution to the Study of Hip-Disease. On the Ultimate Results of the Mechanical and Operative Treatment, with an Analysis of One Hundred and Fifty Cases observed at the Hospital for Ruptured and Crippled. PMID- 17860633 TI - III. The Use of Egg-Membrane in Trephining Operations upon the Skull. PMID- 17860634 TI - IV. The Treatment of Fractures of the Nose. PMID- 17860635 TI - V. Separation of the Upper Epiphysis of the Humerus. PMID- 17860636 TI - VI. Remarks on the Treatment of Tuberculosis of the Uterus and Fallopian Tubes. PMID- 17860637 TI - VII. How to Prevent the Dangers and Disagreeable Symptoms of Ether. PMID- 17860638 TI - VIII. Removal of Biliary Calculi from the Common Duct by the Duodenal Route. PMID- 17860639 TI - IX. Report of Eight Cases of Penetrating Gunshot Wounds of the Abdomen, with Injury to the Hollow Viscera. PMID- 17860640 TI - X. Report of a Case of Stab-Wound of Colon, Diaphragm, and Lung, terminating in Recovery. PMID- 17860642 TI - XII. Report of a Case of Cervical Rib, with Remarks on Mistaken Skiagraphical Diagnoses. PMID- 17860641 TI - XI. A Case of Excessive Bone Atrophy complicating an Ununited Fracture in both Forearms of the same Individual. PMID- 17860643 TI - XIII. Note on Dr. Williams's Paper. PMID- 17860644 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 11, 1898. PMID- 17860645 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, March 11, 1898. PMID- 17860646 TI - I. A Clinical and Histological Study of certain Adenocarcinomata of the Breast: and a Brief Consideration of the Supraclavicular Operation and of the Results of Operations for Cancer of the Breast from 1889 to 1898 at the Johns Hopkins Hospital. PMID- 17860648 TI - III. Posterior Thoracotomy for Foreign Body in the Right Bronchus. PMID- 17860647 TI - II. Observations upon the Operative Treatment of Hernia at the Hospital for the Ruptured and Crippled. PMID- 17860649 TI - IV. The Anatomy and Surgery of the Frontal Sinus and Anterior Ethmoidal Cells. PMID- 17860651 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, May 25, 1898. PMID- 17860650 TI - V. A Case of Complete Cross Lesion of the Spinal Cord due to a Fractured Dislocation. The Fifth Cervical Vertebra being Displaced Forward upon the Sixth. PMID- 17860652 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, June 6, 1898. PMID- 17860653 TI - Rehn on the Suturing of Penetrating Wounds of the Heart. PMID- 17860654 TI - Inflation of the Bladder as a preliminary to Suprapubic Cystotomy. PMID- 17860655 TI - I. Tuberculosis of the Mammary Gland. PMID- 17860656 TI - II. I. Note upon the presence of the Caecum and Appendix in Left Femoral Herniae. II. Case of Inguinal Hernia of Small Intestine without a Peritoneal Sac. PMID- 17860657 TI - III. Epitheliomatosis of the Breast. PMID- 17860658 TI - IV. Venereal Arthropathies. PMID- 17860659 TI - V. A Method for facilitating Enucleation of Tumors of the Thyroid Gland. PMID- 17860661 TI - VII. The Anatomy and Surgery of the Frontal Sinus and Anterior Ethmoidal Cells. PMID- 17860660 TI - VI. A Case of apparently Hopeless Infiltration of Left Axilla and Scapula by Round-Celled Sarcoma; Extirpation attempted and abandoned; Extensive and Severe Wound Infection followed by disappearance of the Tumor. PMID- 17860662 TI - Butlin on Results of Operations for Cancer of the Tongue. PMID- 17860663 TI - I. The Treatment of the Intestinal Paralysis of Peritonitis by Enterostomy. PMID- 17860664 TI - II. Contribution to the Surgery of the Kidney. A Report of Cases treated in the Roosevelt Hospital of New York in the period from January 1, 1890, to October 1, 1898. PMID- 17860665 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 12, 1898. PMID- 17860666 TI - Alsberg on Coxa Vara. PMID- 17860667 TI - The Surgical Occlusion of the Cerebral Sinuses. PMID- 17860668 TI - III. Fractures of the Internal Condyle of the Humerus and the Correction of the Resultant Deformity by Operative Measures. PMID- 17860669 TI - IV. Remarks on the Radical Cure of Hernia. PMID- 17860670 TI - V. Permanent Dislocation of the Patella. The Report of a Case of Twenty Years' Duration, successfully treated by Transplantation of the Patella Tendons with the Tubercle of the Tibia. PMID- 17860671 TI - VI. Fistulous Opening between the Ileum and the Bladder; Operation and Cure. PMID- 17860672 TI - VII. The Anatomy and Surgery of the Frontal Sinus and Anterior Ethmoidal Cells. PMID- 17860673 TI - I. Air-Distention in Operations upon the Biliary Passages. PMID- 17860675 TI - III. Hot Air in Joint-Diseases. PMID- 17860674 TI - II. Postpuerperal Psoitis. PMID- 17860676 TI - IV. Employment of the Needle-Holder whenever in Surgical Operations Suturing is Required. PMID- 17860677 TI - V. Two Cases of Hypertrophy of the Penis; One due to Traumatism; the other, to Elephantiasis. PMID- 17860678 TI - VI. The Anatomy and Surgery of the Frontal Sinus and Anterior Ethmoidal Cells. PMID- 17860680 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 29, 1898. PMID- 17860679 TI - VII. Contribution to the Surgery of the Kidney. A Report of Cases treated in the Roosevelt Hospital of New York in the Period from January 1, 1890, to October 1, 1898. PMID- 17860681 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, October 3, 1898. PMID- 17860682 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, November 7, 1898. PMID- 17860683 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860685 TI - II. The Treatment of Haemorrhoids by the Plastic Method. PMID- 17860684 TI - I. A New Forceps for Intestinal Anastomosis. PMID- 17860686 TI - III. The Technique of Suturing the Patella after Fracture. PMID- 17860687 TI - IV. Prostatectomy. PMID- 17860688 TI - V. Contribution to the Surgery of the Kidney. A Report of Cases treated in the Roosevelt Hospital of New York in the Period from January 1, 1890, to October 1, 1898. PMID- 17860689 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 9, 1898. PMID- 17860690 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 23, 1898. PMID- 17860691 TI - Discussion on Nephrotomy at the French Surgical Congress of 1898. PMID- 17860692 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860693 TI - Enterorrhaphy without Mechanical Accessories. PMID- 17860694 TI - I. On the Management of Acute Traumatic Pneumothorax. PMID- 17860695 TI - II. Cholecystitis: A Clinical Review of Twenty-one Cases. PMID- 17860696 TI - III. A Modification in the Operative Method for Inveterate and Relapsed Cases of Talipes Equino-Varus. PMID- 17860697 TI - IV. Contribution to the Surgery of Empyema of the Thorax in Children. PMID- 17860698 TI - V. The Surgical Treatment of Acute Infective Arthritis and Cellulitis (Acute Articular Rheumatism). PMID- 17860700 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, December 14, 1898. PMID- 17860699 TI - VI. Report of a Case in which Halsted's Hammer was Used as an Aid to the Suture of the Common Bile-Duct. PMID- 17860701 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, December 5, 1898. PMID- 17860703 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860702 TI - The Treatment of Tetanus by Means of Intracerebral Injections of Antitoxin. PMID- 17860704 TI - I. Partial Enterocele. PMID- 17860705 TI - II. Observations on the Use of the Galvanic Current in the Treatment of False Ankylosis. PMID- 17860706 TI - III. Tubercular Cervical Lymph-Nodes: A Study based on Thirty-six Cases submitted to Operation. PMID- 17860707 TI - IV. Decortication of the Tongue in the Treatment of Lingual Psoriasis. PMID- 17860708 TI - V. Congenital Deformity due to Malposition of the Scapula. PMID- 17860709 TI - VI. A Case of Transposed Viscera, with Cholelithiasis, relieved by a Left-Sided Cholecystostomy. PMID- 17860710 TI - VII. Complete Single Sacro-Iliac Dislocation. PMID- 17860711 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, December 28, 1898. PMID- 17860713 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, February 6, 1899. PMID- 17860712 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 11, 1899. PMID- 17860714 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860715 TI - I. Observations in the Sterilization of Catheters and Bougies, and on the Presence of Bacteria in the Urethra. PMID- 17860716 TI - II. Uretero-Ureteral Anastomosis for Traumatism. PMID- 17860718 TI - IV. Preliminary Report on the Surgical Anatomy of the Gall-Bladder and Ducts from an Analysis of One Hundred Dissections. PMID- 17860717 TI - III. Movable Kidney. PMID- 17860719 TI - V. Inspection of the Abdominal Cavity and its Viscera in Post-Mortems. PMID- 17860721 TI - VII. Operative Relief of Vesico-Rectal Fistula. PMID- 17860720 TI - VI. Notes on Cancer of the Fundus Uteri. PMID- 17860722 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 25, 1899. PMID- 17860723 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, March 6, 1899. PMID- 17860725 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860724 TI - Results of Stomach Operations at the Heidelberg Clinic. PMID- 17860726 TI - I. The Technique of Laryngectomy. PMID- 17860727 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, April 3, 1899. PMID- 17860728 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860729 TI - II. On the Surgical Anatomy of the Bile-Ducts and a New Incision for their Exposure. PMID- 17860731 TI - IV. Observations upon Volvulus, with Report of Three Cases submitted to Operation. PMID- 17860730 TI - III. A Comparison of the Merits of Suprapubic and Perineal Cystotomy. PMID- 17860732 TI - V. Inflammation of the Bursa Gastrocnemio-Semimembranosa, with a Report of Four Cases of Enlargement and Distention of this Bursa treated by Excision. PMID- 17860733 TI - VI. The Importance of Blood Examinations in Reference to General Anaesthetization and Operative Procedures. PMID- 17860734 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, February 8, 1899. PMID- 17860735 TI - I. On Two Cases of Traumatic Rupture of the Colon, with some Remarks on the Cases of Rupture of the Intestine treated in the Wards of St. Thomas's Hospital, London, between the Years 1889 and 1898, Inclusive. PMID- 17860736 TI - II. The Treatment of Injuries of the Spinal Cord. PMID- 17860737 TI - III. Observations on the Detection of Small Renal Calculi by the Rontgen Rays. PMID- 17860738 TI - IV. Observations on Nephralgia, with Report of Cases simulating Stone in the Kidney, occurring at the Massachusetts General Hospital. PMID- 17860739 TI - V. Chondrocarcinoma of the Testicle. PMID- 17860741 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 8, 1899. PMID- 17860740 TI - VI. Anterior Dislocation of the Carpal Scaphoid Bone; Congenital Malformation of the Clavicle. PMID- 17860742 TI - Rutkowski on a New Plastic Operation for Exstrophy of the Bladder. PMID- 17860744 TI - I. Gastroplication for Dilated Stomach. PMID- 17860743 TI - Spontaneous Recovery from Gangrenous Littre's Hernia. PMID- 17860745 TI - II. The Intestinal Treatment of Tuberculous Peritonitis. PMID- 17860746 TI - III. Interscapulo-Thoracic Amputation. PMID- 17860747 TI - IV. Report of a Case of Resection of the Liver for the Removal of a Neoplasm, with a Table of Seventy-six Cases of Resection of the Liver for Hepatic Tumors. PMID- 17860749 TI - V. Results and Methods of Treatment of Compound Fractures at the J. Hood Wright Memorial Hospital. PMID- 17860748 TI - THE SURGICAL TREATMENT OF NEOPLASMS OF THE LIVER. PMID- 17860750 TI - VI. Sarcoma of Kidney in an Infant; Recovery after Nephrectomy. PMID- 17860752 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 22, 1899. PMID- 17860751 TI - VII. Splenectomy for Floating Spleen, with Twisted Pedicle. PMID- 17860754 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, May 1, 1899. PMID- 17860753 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 12, 1899. PMID- 17860755 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860756 TI - Remarks on a paper entitled "The Other Kidney in Contemplated Nephrectomy," by George M. Edebohls, M.D. PMID- 17860757 TI - I. On the Surgical Treatment of Haemorrhage from Gastric Ulcers. PMID- 17860758 TI - II. Actinomycosis in Man, with Special Reference to the Cases which have been Observed in America. PMID- 17860760 TI - IV. Observations on the Surgical Anatomy and Methods of Cure of Inguinal Herniae. PMID- 17860759 TI - III. Some Observations on the Surgery of the Gall-Bladder and the Bile-Ducts. PMID- 17860762 TI - VI. Some Experiments Relating to Sterilization of the Hands. PMID- 17860761 TI - V. A Method of Treatment for the Restoration of Entire Tibiae Necrotic from Acute Osteomyelitis. PMID- 17860763 TI - VII. Sterilized Water for Operating Rooms. PMID- 17860765 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 26, 1899. PMID- 17860764 TI - VIII. Strangulated Internal Hernia through a Mesenteric Hole. PMID- 17860766 TI - Surgery of the Heart. PMID- 17860767 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860768 TI - Operative Treatment of Hypospadias. PMID- 17860769 TI - I. Forcible Correction of the Angular Deformity Resulting from Spinal Caries. PMID- 17860770 TI - II. Blastomycetic Dermatitis (Pseudo-Lupus Vulgaris, Saccharomycosis Hominis, or Pseudo-Epithelioma with Blastomycetes). PMID- 17860771 TI - III. Some Remarks on the Symptoms of Bronchocele and the Results of Operative Treatment. PMID- 17860773 TI - V. Successful Removal of a Fibrosarcoma (Desmoid Fibroma) of the Abdominal Wall, involving the Iliac Vessels. PMID- 17860772 TI - IV. On Results Obtainable in the Treatment of some Post-Paralytic Deformities. PMID- 17860774 TI - VI. Sarcoma of the Stomach. PMID- 17860775 TI - VII. Report of a Case of Congenital Inguinal Tele-Lymphangioma of Large Size, with Remarks on Congenital Tumors of Childhood. PMID- 17860776 TI - VIII. Actinomycosis in Man, with Special Reference to the Cases which have been Observed in America. PMID- 17860778 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, May 24, 1899. PMID- 17860777 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, May 10, 1899. PMID- 17860779 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860780 TI - I. Differentiation of the Urines. PMID- 17860781 TI - II. The Mechanism of Fracture of the Neck of the Radius. PMID- 17860783 TI - IV. On the Proper Wire for Introduction into an Aneurismal Sac. PMID- 17860782 TI - III. Properitoneal and Interstitial Inguinal Herniae. PMID- 17860784 TI - V. Nitrous Oxide and Ether Anaesthesia by the Open Method. PMID- 17860785 TI - VI. Note on the Operative Relief of Ectopia Vesicae. PMID- 17860786 TI - VII. Persistent Thyro-Glossal Duct. PMID- 17860788 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860787 TI - VIII. Actinomycosis in Man, with Special Reference to the Cases which have been Observed in America. PMID- 17860789 TI - I. The Employment of Local Anaesthesia in the Radical Cure of Certain Cases of Hernia, with a Note upon the Nervous Anatomy of the Inguinal Region. PMID- 17860791 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860790 TI - The Development of the Surgery of the Kidney, with Some of the Lessons connected therewith. PMID- 17860792 TI - II. Interscapulo-Thoracic Amputation. PMID- 17860793 TI - III. Note on Mortality after Operation for Large Incarcerated Herniae. PMID- 17860794 TI - IV. The Surgical Aspects of the Modern Small-Bore Projectile. PMID- 17860796 TI - VI. On Vesico-Urethro-Vaginal Fistula. PMID- 17860795 TI - V. Mammoth Ovarian Tumors. PMID- 17860797 TI - I. Further Observations on Depression of the Neck of the Femur in Early Life; including Fracture of the Neck of the Femur, Separation of the Epiphysis and Simple Coxa Vara. PMID- 17860798 TI - II. The Technique of the Positive and Negative Diagnosis of Ureteral and Renal Calculi by the Aid of the Rontgen Rays. PMID- 17860799 TI - III. Intestinal Obstruction due to Intussusception. PMID- 17860800 TI - IV. Interscapulo-Thoracic Amputation (Concluded.). PMID- 17860801 TI - V. Pathology of the Lymphatics of the Peritoneum. PMID- 17860802 TI - VI. Traumatic Rupture of the Bile-Duct. PMID- 17860803 TI - VII. Actinomycosis in Man, with Special Reference to the Cases which have been Observed in America Supplementary Report. PMID- 17860804 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 11, 1899. PMID- 17860805 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 25, 1899. PMID- 17860807 TI - TRANSACTIONS OF THE SECTION ON GENERAL SURGERY OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA. Stated Meeting, April 14, 1899. PMID- 17860806 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 8, 1899. PMID- 17860809 TI - II. A New Method of Suture in Operations for Inguinal and other Forms of Hernia. PMID- 17860808 TI - I. Effects of Intracerebral and Subcutaneous Administration of Tetanic Antitoxin in Tetanus as Observed in Nine Cases. PMID- 17860810 TI - III. Fracture of the Neck of the Humerus with Dislocation of the Upper Fragment, with a Report of Three Cases Treated by Operation. PMID- 17860811 TI - IV. Prolapsus of the Rectum in Children. PMID- 17860812 TI - V. Report of Results Obtained in the Treatment of Ununited Fractures with the Parkhill Clamp. PMID- 17860813 TI - VI. A Case of Acute Osteomyelitis of the Femur, with General Systemic Staphylococcus Aureus Infection, Terminating in Recovery. PMID- 17860814 TI - VII. Coccygeal Dermoid Fistula. PMID- 17860815 TI - VIII. Report of a Case of Recovery after Gastrectomy for Carcinoma. PMID- 17860817 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 22, 1899. PMID- 17860816 TI - IX. Two Cases of Cicatricial Stricture of the OEsophagus Treated by Gastrostomy, the "String" Method, and Permanent Dilatation by Elastic Tubes. PMID- 17860818 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860819 TI - I. Surgery in the Presence of Sugar in the Urine. PMID- 17860820 TI - II. On Volvulus in Association with Hernia. PMID- 17860822 TI - IV. On the Use of Fixation Plates in the Treatment of Fractures of the Leg. PMID- 17860821 TI - III. Traumatisms Inflicted by Animals. PMID- 17860823 TI - V. The Relationship between Cholecystitis, Jaundice and Gall-stones. PMID- 17860824 TI - VI. On the Principles Involved in the Immediate Hermetic Sealing of Aseptic Wounds. PMID- 17860825 TI - VII. The Surgery of Gastric Ulcers. PMID- 17860826 TI - VIII. Excision of the External Two-thirds of a Gasserian Ganglion, by the Hartley Krause Method, after Preliminary Ligation of the External Carotid Artery. PMID- 17860828 TI - X. New Operating Table and an Improved Bowl Stand. PMID- 17860827 TI - IX. Two Cases of Anomalous Spinous Process of Seventh Cervical Vertebra Articulating with the Scapula. PMID- 17860829 TI - XI. Conical Stump after Amputation in Childhood. PMID- 17860830 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, December 13, 1899. PMID- 17860831 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, November 6, 1899. PMID- 17860832 TI - Gastro-Enterostomy by the Podrez Method. PMID- 17860833 TI - I. Two Cases of OEsophageal Diverticulum, with Remarks. PMID- 17860834 TI - II. Postdiphtheritic Stenosis of the Larynx (Retained Intubation Instruments and Retained Tracheal Canulae). PMID- 17860835 TI - III. A Contribution to the Surgery of the Stomach, including Wounds, Gastrostomy, Gastro-Enterostomy, and Gastrectomy. PMID- 17860836 TI - IV. Report of a Case of Recovery after Ligation of the First Portion of the Right Subclavian Artery for Aneurism of the Third Portion. PMID- 17860837 TI - V. Complete External Dislocation at the Elbow. PMID- 17860838 TI - VI. Report of a Case of Actinomycosis Hominis of the Lungs. PMID- 17860839 TI - VII. Report of a Case of Superficial Bilateral Gangrene with Asymmetrical Lesions. PMID- 17860841 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, December 27, 1899. PMID- 17860840 TI - VIII. Dislocation at the Shoulder complicated by Fracture through the Anatomical Neck of the Humerus. PMID- 17860842 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 10, 1900. PMID- 17860843 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, December 4, 1899. PMID- 17860844 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860845 TI - I. The Leucocyte Count in Surgery. PMID- 17860846 TI - II. Permanent (Congenital) Dislocation of the Patella. PMID- 17860847 TI - III. Interscapulo-Thoracic Amputation for Osteomyelitis of the Humerus. PMID- 17860848 TI - IV. Thyroid Medication in the Treatment of Delayed Union of Fractures. PMID- 17860849 TI - V. Splenectomy for Congestive Hypertrophy. PMID- 17860851 TI - VII. Radical Treatment for Curvature of the Penis. PMID- 17860850 TI - VI. Operation for Cure of Large Incarcerated Hernia of Long Standing. PMID- 17860852 TI - VIII. Report of a Case of Exstrophy of the Bladder, with Remarks upon the Operative Treatment of that Condition. PMID- 17860854 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, February 14, 1900. PMID- 17860853 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 24, 1900. PMID- 17860855 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, February 28, 1900. PMID- 17860856 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860857 TI - I. Perforating Ulcer of the Stomach. PMID- 17860858 TI - VI. Adhesions about the Stomach. PMID- 17860859 TI - VII. Note on a Case of Syphilis Terminating in Death. PMID- 17860861 TI - II. Benign Obstruction of the Pylorus. PMID- 17860860 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. 14, 1900: Stated Meeting, March. PMID- 17860862 TI - III. The Surgical Treatment of Simple Dilatation of the Stomach and of Gastroptosis. PMID- 17860863 TI - IV. Hour-Glass Stomach, and Its Surgical Treatment. PMID- 17860864 TI - V. The Diagnosis of Cancer of the Stomach. PMID- 17860866 TI - II. A Critical Survey of Ureteral Implantations. PMID- 17860865 TI - I. The best Method of Collecting the Urine from the Ureters for Diagnostic Purposes. PMID- 17860867 TI - III. The Pathology of Fracture of the Lower Extremity of the Radius. PMID- 17860868 TI - IV. Tetanus. A Study of the Nature, Excitant Lesions, Symptomatology, and Treatment of the Disease, with a Critical Summary of the Results of Serum Therapy. PMID- 17860869 TI - V. Malignant Diseases of the Stomach and Pylorus. PMID- 17860870 TI - VI. Note on the Relation of the Os Magnum to Tuberculosis of the Wrist-Joint. PMID- 17860872 TI - VIII. Report of a Case of Strangulated Obturator Hernia. PMID- 17860871 TI - VII. A Method of Excision of the Shoulder-Joint. PMID- 17860873 TI - IX. Report of a Case of Irreducible Backward Dislocation of the Bones of the Leg at the Knee-Joint. PMID- 17860874 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. 28, 1900: Stated Meeting, March. PMID- 17860875 TI - I. Cubitus Varus; or, "Gunstock" Deformity following Fracture of the Lower End of the Humerus. PMID- 17860877 TI - III. Massage in the Treatment of Recent Periarticular Fractures. PMID- 17860876 TI - II. The Results of Castration and Vasectomy in Hypertrophy of the Prostate Gland. PMID- 17860878 TI - IV. Excision of the Wrist by a Modification of Mynter's Method. PMID- 17860879 TI - V. The Ileocaecal Orifice and its Bearing on Chronic Constipation, with Report of Two Cases relieved by Operation. PMID- 17860880 TI - VI. Hernia of the Bladder through the Pelvic Floor from the Traction of a Subperitoneal Fibroma. PMID- 17860881 TI - VII. On the Influence of Anaesthesia on the Effect produced on the Circulation and Respiration by Irritation of a Sensory Nerve. PMID- 17860882 TI - VIII. The Pathology of Fracture of the Lower Extremity of the Radius. PMID- 17860883 TI - IX. Tetanus A Study of the Nature, Excitant, Lesions, Symptomatology, and Treatment of the Disease, with a Critical Summary of the Results of Serum Therapy. PMID- 17860885 TI - On the Co-operation of Surgeons in the Making of Surgical History. PMID- 17860884 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. 11, 1900: Stated Meeting, April. PMID- 17860886 TI - I. The Surgical Treatment of Primary Renal Tuberculosis, with a Consideration of the Immediate and Remote Results after Operation. PMID- 17860887 TI - II. A Study of One Thousand Operations for Acute Intestinal Obstruction and Gangrenous Hernia. PMID- 17860888 TI - III. Mesenteric Cysts. PMID- 17860889 TI - IV. Dislocation of the Humerus, complicated by Fracture at or near the Surgical Neck. PMID- 17860890 TI - V. Remarks on the Technique of Prostatectomy, with Report of a Case. PMID- 17860891 TI - VI. Suprapubic Retrocystic Extraperitoneal Resection of the Seminal Vesicles, Vasa Deferentia, and half of the Bladder. PMID- 17860892 TI - VII. Excision of the Right Vas Deferens and Vesicula Seminalis for Secondary Tubercular Disease. PMID- 17860894 TI - IX. Tetanus A Study of the Nature, Excitant, Lesions, Symptomatology, and Treatment of the Disease, with a Critical Summary of the Results of Serum Therapy. PMID- 17860893 TI - VIII. A New Method of Colpoplasty in a Case of Entire Absence of the Vagina. PMID- 17860895 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , April 25, 1900: Stated Meeting. PMID- 17860896 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , May 9, 1900: Stated Meeting. PMID- 17860897 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , January 8, 1900: Stated Meeting. PMID- 17860898 TI - I. A Skiagraphic Study of the Normal Membral Epiphyses at the Thirteenth Year. PMID- 17860899 TI - II. A Contribution to the Study of Intra-Abdominal Omental Torsion. PMID- 17860900 TI - III. Retrenchment of Lipomatous Abdominal Wall combined with Operation for Radical Cure of Umbilical Hernia. PMID- 17860901 TI - IV. Report of a Case of Actinomycosis Hominis. PMID- 17860902 TI - V. Traumatic Rupture of the Small Intestine; Abdominal Section; Recovery. PMID- 17860904 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , May 23, 1900: Stated Meeting. PMID- 17860903 TI - VI. A Study of One Thousand Operations for Acute Intestinal Obstruction and Gangrenous Hernia (Concluded.). PMID- 17860905 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , February 1900: Stated Meeting. PMID- 17860906 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860907 TI - I. Structure, Fracture, and Refracture of the Patella. PMID- 17860908 TI - II. Suppurative Pericarditis and Its Surgical Treatment, with an Analysis of Fifty-one Cases Reported in Literature. PMID- 17860909 TI - III. The Radical Cure of Inguinal Hernia in the Female. PMID- 17860910 TI - IV. Echinococcus Cyst of the Liver. PMID- 17860911 TI - V. A Complete Series of Clinical Charts for Keeping the Records of Surgical Cases. PMID- 17860912 TI - VI. Result of Operation for Cancer of Penis. PMID- 17860914 TI - VIII. Transperitoneal Ureterolithotomy. Report of a Case in which the Stone was Located by the X-Ray. PMID- 17860913 TI - VII. Fracture of the Spine. PMID- 17860915 TI - Surgical Analgesia by Spinal Cocainization. PMID- 17860916 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860917 TI - The Technique of Prostatectomy. PMID- 17860919 TI - II. On Traumatic Keloid of the Median Nerve, with Observations upon the Absorption of Silk Sutures. PMID- 17860918 TI - I. Ventral Hernia following Abdominal Section. PMID- 17860920 TI - III. An Intestine Holder. Devised for Facilitating the End-to-End Suture of Intestine. PMID- 17860921 TI - IV. Laryngectomy under Eucaine Anaesthesia, with Remarks on the Technique of the Operation. PMID- 17860922 TI - V. Double Ureter. Report of a Nephrectomy done upon a Young Child with this Condition Present. PMID- 17860923 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 10, 1900: Stated Meeting. PMID- 17860924 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 24, 1900: Stated Meeting. PMID- 17860925 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , March 5, 1900: Stated Meeting. PMID- 17860926 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , April 2, 1900: Stated Meeting. PMID- 17860927 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , October 4, 1900: Stated Meeting. PMID- 17860929 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860928 TI - Results Obtainable in the Treatment of Dense, Tight, Deep-Lying Strictures of the Urethra. PMID- 17860930 TI - I. Gunshot Wounds in the Philippino-American War. PMID- 17860931 TI - II. Sarcoma of the Uterus. PMID- 17860932 TI - III. Contribution to the Surgery of Multilocular Renal Cyst. PMID- 17860933 TI - IV. Cicatricial Stricture of Pharynx cured by Plastic Operation. PMID- 17860934 TI - V. The Improved Technique in the Operative Surgery of Carcinoma of the Stomach. PMID- 17860935 TI - VI. Cases of Compound or Complicated Fracture Illustrating the Value of Operative Interference in the Treatment of these Injuries. PMID- 17860936 TI - VII. A Method of performing Anastomosis of Hollow Viscera by a New Instrument. PMID- 17860937 TI - VIII. I. An Improved Brace for Head Extension. II. A Hard Rubber Spring Brace for Lateral Curvature. PMID- 17860938 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , November 14, 1900: Stated Meeting. PMID- 17860940 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , June 4, 1900: Stated Meeting. PMID- 17860939 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , May 7, 1900: Stated Meeting. PMID- 17860941 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860942 TI - I. On Non-Obstructive, Postoperative Anuria. PMID- 17860943 TI - II. Diagnosis of Stone in the Kidney by the X-Ray, and its Treatment. PMID- 17860944 TI - III. Hernia of the Fallopian Tube without Hernia of the Ovary. PMID- 17860945 TI - IV. Contributions to the Surgery of Malignant Disease of the Prostate Gland and of the Tonsils. PMID- 17860946 TI - V. Resection of the Pendulous, Fat Abdominal Wall in Cases of Extreme Obesity. PMID- 17860947 TI - VI. Eversion of the Tunica Vaginalis as a Remedy for Hydrocele. PMID- 17860948 TI - VII. Report of a Case of Recovery after Abdominal Section for Multiple Gunshot Wounds of the Abdomen: Perforations of Liver, Gall-Bladder, Hepatic Flexure of Colon, Two of the Small Intestines, One of Rectum (Deep in Pelvis), with Active and Excessive Haemorrhage. PMID- 17860949 TI - VIII. Periosteal Osteosarcoma of Upper Extremity of Femur; Ligation of Common Iliac Artery, with Amputation at Hip-Joint and Removal of Portion of Pelvis, etc.; Recovery, with Freedom from Recurrence at End of nearly Sixteen Months. PMID- 17860950 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , November 28, 1900: Stated Meeting. PMID- 17860951 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , November 2, 1900: Stated Meeting. PMID- 17860953 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860952 TI - Critical Suggestions on Cleansing the Surgeon's Hands. PMID- 17860954 TI - I. Conservative Operations for Renal Retention. PMID- 17860955 TI - II. The Appendix in Relation to the Psoas Muscle in Three Hundred Male and One Hundred and Eighteen Female Adult Autopsies. Trauma of the Psoas Muscle produces Appendicitis. PMID- 17860956 TI - III. The Value of the Rontgen Method of Diagnosis in Detecting and Excluding Renal and Ureteral Calculi. PMID- 17860957 TI - IV. Ileus due to Vascular Obstruction. PMID- 17860958 TI - V. Ileus due to Mechanical Obstruction to the Faecal Current. PMID- 17860959 TI - VI. Ileus caused by Neoplasms. PMID- 17860960 TI - VII. Fissure of the Head of the Radius. PMID- 17860961 TI - VIII. Excision of the Cervical Sympathetic Ganglia for Exophthalmic Goitre. PMID- 17860962 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , December 12, 1900: Stated Meeting. PMID- 17860963 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , December 5, 1900: Stated Meeting. PMID- 17860964 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860966 TI - II. Concerning Prompt Surgical Intervention for Intestinal Perforation in Typhoid Fever, with the Relation of a Case. PMID- 17860965 TI - I. The Surgery of the Spleen. PMID- 17860968 TI - IV. Hydatid of the Prostate. PMID- 17860967 TI - III. Operative Paralysis of the Spinal Accessory Nerve. PMID- 17860969 TI - V. The Surgical Treatment of Amoebic Dysentery. PMID- 17860971 TI - VII. Some Errors in Diagnosis in Conditions Resembling Appendicitis. PMID- 17860970 TI - VI. Some New Points in Tendon Surgery. PMID- 17860972 TI - VIII. Rare Complications after Operations for Appendicitis. PMID- 17860974 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , December 26, 1900: Stated Meeting. PMID- 17860973 TI - IX. Report of Three Cases of Properitoneal Hernia. PMID- 17860976 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , October 1, 1900: Stated Meeting. PMID- 17860975 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , January 9, 1901: Stated Meeting. PMID- 17860977 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , January 4, 1901: Stated Meeting. PMID- 17860978 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860979 TI - I. A Loop Around the Hyoid Bone as an Aid in Narcosis during Certain Operations on the Lower Jaw and in the Mouth, and in After-Treatment. PMID- 17860980 TI - II. Excision of the Intact Gasserian Ganglion: With a Report of Two Cases of Trifacial Neuralgia Successfully Treated by this Means. PMID- 17860981 TI - III. The Pathology of Trigeminal Neuralgia, Illustrated by the Microscopic Examination of Two Gasserian Ganglia. PMID- 17860982 TI - IV. Osteoplastic Amputation of the Arm: With the Description of a Useful Saw for Osteoplastic Amputations. PMID- 17860983 TI - V. Cases of Laceration of the Spleen and of the Kidney followed by Recovery after Removal of the Injured Organ. PMID- 17860984 TI - VI. The Operative Treatment of Cirrhosis of the Liver. PMID- 17860985 TI - VII. Angina Ludovici. PMID- 17860986 TI - VIII. Complications in Fractures Involving the Hip-Joint. PMID- 17860987 TI - IX. Fracture of the Pelvis: A Report of Fifty-Four Cases. PMID- 17860988 TI - X. A New Knot-Tightener. PMID- 17860989 TI - XI. The Value of the X-Ray in Surgery. PMID- 17860990 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , January 23, 1901: Stated Meeting. PMID- 17860991 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , November 5, 1900: Stated Meeting. PMID- 17860992 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , December 3, 1900: Stated Meeting. PMID- 17860993 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , February 1, 1901: Stated Meeting. PMID- 17860994 TI - INDEX TO SURGICAL PROGRESS. PMID- 17860995 TI - I. Radical Cure of Inguinal and Femoral Hernia, with a Report of Eight Hundred and Forty-five Cases. PMID- 17860996 TI - VI. Splenectomy in Splenic Anaemia or Primary Splenomegaly. PMID- 17860997 TI - VII. The Best Incision in Operations for Mammary Carcinoma. PMID- 17860998 TI - VIII. Aneurism of the Thoracic Aorta of Traumatic Origin; Treatment by Introduction of Wire and Electricity. PMID- 17860999 TI - IX. Left Caecal Hernia, with a Report of Two Cases. PMID- 17861000 TI - X. The Treatment of Suppurating Haematocele Due to Extra-Uterine Pregnancy. PMID- 17861001 TI - XI. The Mortality of Operation for Obstructive Jaundice. PMID- 17861002 TI - XII. Report of a Case of Recovery from Perforating Typhoid Ulcer of Intestine after Operation. PMID- 17861003 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , February 13, 1901: Stated Meeting. PMID- 17861004 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , January 7, 1901: Stated Meeting. PMID- 17861005 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , March 8, 1901: Stated Meeting. PMID- 17861006 TI - II. Two Cases of Ligation of the External Carotid for Severe Haemorrhage,-One after Tonsillotomy, the Other after a Slight Intranasal Operation. PMID- 17861007 TI - III. The Operative Treatment for Exstrophy of the Bladder. PMID- 17861008 TI - IV. The Treatment of Fracture of the Neck of the Femur. PMID- 17861009 TI - V. Wounds of the Venous Sinuses of the Brain An Analysis of Seventy Cases. PMID- 17861010 TI - I. Intraperitoneal Rupture of the Bladder treated by Laparotomy and Suture Report of Forty-five Cases. PMID- 17861011 TI - II. Strangulation of the Testis by Torsion of the Cord. A Review of All Recorded Cases, together with the Report of One Recent Case. PMID- 17861012 TI - III. Fracture of the Carpal End of the Radius, with Fissure or Fracture of the Lower End of the Ulna, and Other Associated Injuries. PMID- 17861013 TI - IV. An Operation for Saddle Nose. PMID- 17861014 TI - V. The Artificial Production of Connective Tissue by Means of Injection of Agar Agar. PMID- 17861015 TI - VI. An Operation for the Radical Cure of Umbilical Hernia. PMID- 17861016 TI - VII. Sarcoma of the Wall of the Thorax. Successful Excision of a Part of Three Ribs and a Portion of the Diaphragm. PMID- 17861017 TI - VIII. Congenital Anterior Dislocation of the Tibia treated by Arthrotomy. PMID- 17861018 TI - IX. Cancrum Oris Successfully treated by Excision of the Cautery. PMID- 17861019 TI - X. Forward Dislocation of the Semilunar Bone. PMID- 17861020 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , February 27, 1901: Stated Meeting. PMID- 17861022 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , February 4, 1901: Stated Meeting. PMID- 17861021 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , March 13, 1901: Stated Meeting. PMID- 17861023 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , March 4, 1901: Stated Meeting. PMID- 17861024 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , April 5, 1901: Stated Meeting. PMID- 17861025 TI - I. The Blood Changes Induced by the Administration of Ether as an Anaesthetic: A Contribution from the Laboratories of the Jefferson Medical College Hospital. PMID- 17861026 TI - II. Studies of the Blood in its Relation to Surgical Diagnosis. PMID- 17861027 TI - III. Frequency of Recurrence of Sarcoma: With Especial Reference to Amputation at the Hip-Joint on Account of this Neoplasm. PMID- 17861028 TI - IV. Teratoma of the Testis. PMID- 17861029 TI - V. Sacculated Aneurism of the Superior Profunda Humeri Artery. PMID- 17861030 TI - VI. Fracture of the Skull. PMID- 17861031 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , March 27, 1901: Stated Meeting. PMID- 17861032 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , April 10, 1901: Stated Meeting. PMID- 17861033 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , March 4, 1901: Stated Meeting. PMID- 17861034 TI - INDEX TO SURGICAL PROGRESS. PMID- 17861035 TI - I. A Contribution to the Pathology of the Sphincters. PMID- 17861036 TI - II. Milton's Method of Exposing the Anterior Mediastinum Modified for Ligature of the Innominate Artery. PMID- 17861038 TI - IV. Foreign Bodies Accidentally left in the Abdominal Cavity: With Report of One Hundred and Fifty-Five Cases. PMID- 17861037 TI - III. Abscess of the Liver. PMID- 17861039 TI - V. The Worsted Truss in Inguinal Hernia. PMID- 17861041 TI - VII. Some Observations on Fractures of the Skull, Based on One Hundred and Forty six Cases. PMID- 17861040 TI - VI. Pneumococcus Arthritis, Primary in the Knee-Joint. PMID- 17861042 TI - VIII. Suppurative Pericarditis following Appendicitis; Recovery after Incision and Drainage of Pericardium. PMID- 17861043 TI - IX. A Report of Two Cases of Facial Anthrax Treated by Injections of Carbolic Acid, with Recovery. PMID- 17861044 TI - X. The X-Ray and Photographic Technique Necessary to bring out Bone Detail in the Print. PMID- 17861046 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , April 1, 1901: Stated Meeting. PMID- 17861045 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , April 24, 1901: Stated Meeting. PMID- 17861047 TI - Intraperitoneal Rupture of the Bladder. PMID- 17861048 TI - I. Genital Tuberculosis, with Special Reference to the Seminal Vesicles. Report of Two Cases of Spermatocystectomy. PMID- 17861049 TI - II. Cervical Ribs. PMID- 17861051 TI - IV. Anorectal Transplantation. PMID- 17861050 TI - III. Skin-grafting in the Treatment of Complete Stenosis of the Larynx. PMID- 17861052 TI - V. Acute Intestinal Obstruction following Appendicitis. A Report of Three Cases Successfully Operated upon. PMID- 17861054 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , May 8, 1901: Stated Meeting. PMID- 17861053 TI - VI. Foreign Bodies Accidentally left in the Abdominal Cavity. With Report of One Hundred and Fifty-five Cases. PMID- 17861055 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , May 6, 1901: Stated Meeting. PMID- 17861056 TI - I. A Contribution to the Pathology, Diagnosis, and Treatment of Subphrenic Abscesses after Appendicitis. PMID- 17861057 TI - II. On the Differentiation between Inflammatory Processes and Neoplasms of the Bones by the Rontgen Rays. PMID- 17861059 TI - IV. Treatment of Tuberculosis of the Peritoneum. PMID- 17861058 TI - III. On the Pathology, Symptomatology, and Diagnosis of Tuberculosis of the Peritoneum. PMID- 17861060 TI - V. Tuberculosis Herniosa and Appendicitis Tuberculosa. PMID- 17861061 TI - VI. Obturator Hernia of the Bladder and of the Fallopian Tube. PMID- 17861062 TI - VII. Note on X-Ray Burns and their Treatment. PMID- 17861063 TI - VIII. Contribution to the Surgery of True Cystic Kidney. PMID- 17861064 TI - IX. Ureteral Anastomosis. Report of a Successful Case. PMID- 17861065 TI - X. Stone in the Bladder of a Female Child of Four Years. PMID- 17861066 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , May 22, 1901: Stated Meeting. PMID- 17861067 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , May 3, 1901: Stated Meeting. PMID- 17861068 TI - INDEX TO SURGICAL PROGRESS. PMID- 17861070 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 9, 1901: Stated Meeting. PMID- 17861069 TI - I. The Cause of "Stitch Abscesses" and their Prevention. Sterilization of the Skin prior to Operation by Inunctions of Oleate of Mercury. PMID- 17861071 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , October 7, 1901: Stated Meeting. PMID- 17861072 TI - II. Report of Six Cases of Penetrating Wounds of the Abdomen submitted to Abdominal Section, with Statistical Tables of One Hundred and Fifty-two Cases thus Operated on at the Charity Hospital in New Orleans, La. PMID- 17861073 TI - III. The Technique of Gall-Bladder and Duct Operations. PMID- 17861074 TI - IV. Intussusception of Meckel's Diverticulum. PMID- 17861075 TI - V. Mechanical versus Suture Methods for Intestinal Approximation. PMID- 17861076 TI - VI. The Symptomatology, Diagnosis, and Treatment of Carcinoma of the Caecum, with a Report of Two Cases. PMID- 17861077 TI - VII. Elbow Fractures in Children. Fractures of the Lower End of the Humerus; Lesions and End Results, and their Bearing upon Treatment. PMID- 17861078 TI - I. The Technics of Nephropexy, as an Operation per se, and as Modified by Combination with Lumbar Appendicectomy and Lumbar Exploration of the Bile Passages. PMID- 17861079 TI - II. Note on the Distribution of the Branches of the Internal Iliac Artery and the Zones of Exsanguination Resulting from its Deligation. PMID- 17861081 TI - IV. The Symptomatology, Diagnosis, and Treatment of Carcinoma of the Caecum, with a Report of Two Cases. PMID- 17861080 TI - III. Ligation of the Abdominal Aorta for Aneurism. PMID- 17861082 TI - V. Elbow Fractures in Children. Fractures of the Lower End of the Humerus; Lesions and End Results, and their Bearing upon Treatment. PMID- 17861083 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 23, 1901: Stated Meeting. PMID- 17861084 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , November 4, 1901: Stated Meeting. PMID- 17861085 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , November 1, 1901: Stated Meeting. PMID- 17861086 TI - I. Suture of the Abdominal Wall. PMID- 17861087 TI - II. Epiplopexy in Cirrhosis of the Liver with Ascites. PMID- 17861088 TI - III. On Splanchnoptosis and its Surgical Treatment, with Report of a Case. PMID- 17861089 TI - IV. Abdominal Contusions Associated with Rupture of the Intestine. PMID- 17861090 TI - V. Traumatic Rupture of the Mesenteric Arteries. PMID- 17861091 TI - VI. The Surgical Treatment of Some of the Remote Results of Inflammation of the Gall-Bladder and Bile-Ducts. PMID- 17861092 TI - VII. An Instrument for Facilitating Intestinal Anastomosis. PMID- 17861093 TI - VIII. Misapplied Mechanical Support to Weak Ankles of Children. PMID- 17861094 TI - IX. Elbow Fractures in Children. Fractures of the Lower End of the Humerus; Lesions and End Results, and their Bearing upon Treatment. PMID- 17861095 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , November 13, 1901: Stated Meeting. PMID- 17861096 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 27, 1901. PMID- 17861097 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , December 2, 1901: Stated Meeting. PMID- 17861098 TI - INDEX TO SURGICAL PROGRESS. PMID- 17861099 TI - I. An Experimental and Clinical Research on the Temporary Closure of the Carotid Arteries. PMID- 17861100 TI - II. Stereoscopic Radiography. PMID- 17861101 TI - III. Prostatectomy by the Perineal Route. PMID- 17861102 TI - IV. Intestinal Obstruction from Meckel's Diverticulum. PMID- 17861104 TI - VI. Hernia of Meckel's Diverticulum. PMID- 17861103 TI - V. Meckel's Diverticulum Patent at the Navel. PMID- 17861105 TI - VII. Bone Cysts. A Case in which the Humerus was Involved, with the X-Ray and Microscopic Findings. PMID- 17861107 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , December 2, 1901: Stated Meeting. PMID- 17861106 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , December 11, 1901: Stated Meeting. PMID- 17861108 TI - Korte on the Surgical Treatment of Gastric Ulcer and its Sequelae (Pyloric Stenosis, Gastric Dilatation, Haemorrhage). PMID- 17861109 TI - INDEX TO SURGICAL PROGRESS. PMID- 17861110 TI - I. Thoracic Injuries involving the Lungs. PMID- 17861111 TI - II. Fracture of the Carpal Scaphoid with Dislocation Forward of the Central Fragment. PMID- 17861112 TI - III. Treatment of Dislocation of the Clavicle through Open Wound. PMID- 17861113 TI - IV. Subcutaneous Injury of the Brachial Plexus. PMID- 17861114 TI - V. Chronic Phagedaena due to Mixed Infection. PMID- 17861115 TI - VI. Hour-Glass Stomach. PMID- 17861116 TI - VII. Rupture of the Axillary Vein in reducing an Old Dislocation of the Shoulder. PMID- 17861117 TI - VIII. Pus Dilatation of One Member of a Double Ureter. PMID- 17861118 TI - IX. Intestinal Suture: Report of Five Consecutive Cases Illustrating Different Methods of Suture. PMID- 17861120 TI - XI. Contribution to the Surgery of Spina Bifida. PMID- 17861119 TI - X. The Curative Effect of Trephining per se: Two Cases Trephined for Intracranial Disease,-One Cured, the Other Markedly Benefited; in neither was a Lesion Found, nor were the Operations Made Over the Areas which the Symptoms Suggested might be Diseased. PMID- 17861121 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , January 8, 1902: Stated Meeting. PMID- 17861122 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , January 22, 1902: Stated Meeting. PMID- 17861123 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , February 12, 1902: Stated Meeting. PMID- 17861125 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , January 6, 1902: Stated Meeting. PMID- 17861124 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , January 3, 1902: Stated Meeting. PMID- 17861127 TI - INDEX TO SURGICAL PROGRESS. PMID- 17861126 TI - Clayton Parkhill, Anatomist and Surgeon. PMID- 17861128 TI - I. Fracture of the Base of the Fifth Metatarsal Bone by Indirect Violence. PMID- 17861129 TI - II. Studies in the Pathogenesis of Appendicitis. PMID- 17861130 TI - III. Clinical Observations on the Surgery of the Gall-Bladder. PMID- 17861131 TI - IV. Analysis of Three Hundred and Twenty-Eight Operations upon the Gall-Bladder and Bile Passages. PMID- 17861132 TI - V. The Surgical Aspects of the Status Lymphaticus. PMID- 17861133 TI - VI. Abscesses in the Right Iliac Region, and Other Lesions not of Gynaecologic or Appendiceal Origin Mistaken for Appendicitis: With Reports of One Hundred and Ninety-Four Cases, with Lesions of Twenty Varieties of Structure and Sixty-Eight Species of Lesion, Not One of the Numbered Cases of Appendiceal Origin and all so Mistaken; Seven Cases Hitherto Unreported. PMID- 17861134 TI - VII. Sarcoma of the Mesentery: Resection of One Hundred and Nineteen Inches of Small Intestine; Recovery. PMID- 17861135 TI - VIII. Haemostasis of the Broad Ligament. PMID- 17861136 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , February 26, 1902: Stated Meeting. PMID- 17861137 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , February 3, 1902: Stated Meeting. PMID- 17861138 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , February 3, 1902: Stated Meeting. PMID- 17861139 TI - The Predisposing and Exciting Causes of Sudden Attacks of Appendicitis. PMID- 17861140 TI - I. Foreign Bodies in the Lungs. PMID- 17861141 TI - XII. Intestinal Polyposis and Carcinoma. PMID- 17861142 TI - XIII. Bony Cysts of the Middle Turbinated Body. PMID- 17861143 TI - XIV. Subacromial Dislocation from Muscular Spasm. PMID- 17861144 TI - XV. The Role of the Bacillus Proteus Vulgaris in Surgery. PMID- 17861145 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , March 12, 1902: Stated Meeting. PMID- 17861146 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , March 3, 1902: Stated Meeting. PMID- 17861148 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , March 5, 1902: Stated Meeting. PMID- 17861147 TI - II. Ligation of the Lingual Artery through the Mouth in Excising Half of the Tongue. PMID- 17861149 TI - III. The Treatment of Prostatic Hypertrophy Associated with Stone in the Bladder by Means of Litholapaxy and Bottini's Operation at One Sitting. PMID- 17861150 TI - IV. Transvesical Cauterization as a Substitute for the Bottini Operation in the Treatment of Some Forms of Prostatic Hypertrophy. PMID- 17861151 TI - V. Traumatic Rupture of the Spleen; Splenectomy; Death on the Sixth Day. PMID- 17861152 TI - VI. Gangrenous Intussusception in a Child Four Years Old; Intestinal Resection; Recovery: The Value of End-to-End Suture with an Inner Row of Stitches Through All the Layers of the Intestine and an Outer Row Through the Outer Layers. PMID- 17861154 TI - VIII. Osteoplastic Resection of the Skull by Means of a New Trephine. PMID- 17861153 TI - VII. The Operative Treatment of Diseases of the Pancreas. PMID- 17861155 TI - IX. Motor Aphasia due to a Small Cortical Haemorrhage in the Region of Broca's Convolution; Trephining; Recovery. PMID- 17861156 TI - X. Operations upon the Kidney at the German Hospital in Philadelphia. PMID- 17861157 TI - XI. Hydatid Cysts of the Kidney. PMID- 17861159 TI - II. Angiotripsy as a Substitute for the Ligature in Routine Work of General Surgery. PMID- 17861158 TI - I. Intestinal Obstruction due to Gall-Stones. Report of Three Cases, with Summary of Five More Cases from the Records of the London Hospital, 1893-1901. PMID- 17861160 TI - III. Morrison's Operation for Ascites due to Laennec's Cirrhosis. PMID- 17861161 TI - IV. Congenital Dislocation of Hips With Report of Cases and Description of a Pelvis obtained Three Years after Successful Reduction by the Lorenz Method. PMID- 17861162 TI - V. On the Use of the Abdominal Route for Approaching Rectal Tumors. PMID- 17861163 TI - VI. A Case of Perforating Gunshot Wound of the Stomach and Liver with Posterior Through Drainage and Recovery. PMID- 17861165 TI - VIII. Report of Five Cases of Laparotomy for Intestinal Obstruction. PMID- 17861164 TI - VII. Complications following Gastro-enterostomy. PMID- 17861167 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , March 26, 1902: Stated Meeting. PMID- 17861166 TI - IX. On a Case of Splenectomy for Leukaemic Enlargement. PMID- 17861168 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , April 9, 1902: Stated Meeting. PMID- 17861169 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , April 7, 1902: Stated Meeting. PMID- 17861170 TI - INDEX TO SURGICAL PROGRESS. PMID- 17861171 TI - I. On the Avoidance of Shock in Major Amputations by Cocainization of Large Nerve Trunks Preliminary to their Division. With Observations on Blood-Pressure Changes in Surgical Cases. PMID- 17861172 TI - II. Subparietal Rupture of the Kidney. PMID- 17861173 TI - III. The Results of Wounds of the Large Joints made by Modern Military Projectiles. PMID- 17861174 TI - IV. Removal of the Superior Cervical Ganglion for the Relief of Glaucoma, with Report of a Case. PMID- 17861175 TI - V. Note on Synchronous Ligation of Both Internal Jugular Veins. PMID- 17861176 TI - VI. Operative Treatment of Exophthalmic Goitre. PMID- 17861177 TI - VII. Avulsion of the Brachial Plexus, with a Report of Three Cases. PMID- 17861178 TI - VIII. Note on Permanent Suprapubic Drainage for Advanced Tuberculosis of the Bladder: Report of a Case at End of Five Years. PMID- 17861180 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , April 23, 1902: Stated Meeting. PMID- 17861179 TI - IX. Anatomical and Technical Reasons why the Perineal is Preferable to the Suprapubic Route in Prostatic Surgery. PMID- 17861181 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , May 5, 1902: Stated Meeting. PMID- 17861182 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , April 7, 1902: Stated Meeting. PMID- 17861183 TI - INDEX TO SURGICAL PROGRESS. PMID- 17861184 TI - I. Fatal Acetonaemia following an Operation for Acute Appendicitis. PMID- 17861185 TI - II. Acute Suppurative Pancreatitis. PMID- 17861186 TI - III. Cholecystectomy versus Removal of the Mucous Membrane of the Gall-Bladder. PMID- 17861187 TI - IV. Removal of the Bladder and Prostate for Carcinoma through a Suprapubic Opening. PMID- 17861188 TI - V. Results of Operations on the Kidney for Tuberculosis. PMID- 17861189 TI - VI. Valve Formation in the Lower Portion of the Ureter. PMID- 17861190 TI - VII. Excision of the Lumbar Lymphatic Nodes and Spermatic Vein in Malignant Disease of the Testicle: A Contribution from the Surgical Laboratory of the Philadelphia Polyclinic. PMID- 17861191 TI - VIII. Report of a Case of Gunshot Wound of the Thorax involving the Heart. PMID- 17861193 TI - X. Contribution to the Surgery of Cleft Palate. A Uranostaphylorrhaphy suitable for Certain Conditions. PMID- 17861192 TI - IX. Measurements for Operating Distances in the Nose. PMID- 17861194 TI - XI. Total Excision of the Scapula, with Preservation of the Upper Extremity. PMID- 17861195 TI - XII. A Further Note on Interscapulo-Thoracic Amputations. PMID- 17861196 TI - XIII. Operative Dislocation of the Head of the Femur in Tubercular Disease of the Acetabulum. PMID- 17861197 TI - XIV. Contribution to the Pathology of Supra-Acromial Dislocation of the Clavicle and Obturator Dislocation of the Hip. PMID- 17861198 TI - XV. A Case of Trigger Fingers. PMID- 17861199 TI - XVI. The Hartley-Krause Flap in Haemorrhage from the Middle Meningeal Artery. With Reports of Two Cases. PMID- 17861201 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , May 5, 1902: Stated Meeting. PMID- 17861200 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , May 14, 1902: Stated Meeting. PMID- 17861203 TI - INDEX TO SURGICAL PROGRESS. PMID- 17861202 TI - The Healing of Nerves. PMID- 17861204 TI - I. The Technique of Prostatectomy. PMID- 17861206 TI - III. A Contribution to the Surgical Anatomy of the Middle Cranial Fossa: With Special Reference to Operations for the Removal of the Gasserian Ganglion. PMID- 17861207 TI - IV. The "Circulus Vitiosus" following Gastro-Enterostomy: With a Description of a New Operation Designed to Prevent its Occurrence. PMID- 17861205 TI - II. The Prerectal Curvilinear Incision for Prostatic Abscess; with a Report of Three Cases. PMID- 17861209 TI - VI. Perforation of the Bowel in Typhoid Fever. PMID- 17861208 TI - V. So-called Hypertrophic Tuberculosis of the Intestine. PMID- 17861210 TI - VII. A New Method of Treatment for Fracture of the Neck of the Femur, together with Remarks on Coxa Vara. PMID- 17861212 TI - IX. The Implantation of Silver Filigree for the Closure of Large Hernia Apertures. PMID- 17861211 TI - VIII. The Identity of Proteus Infection and Hospital Gangrene: A Case of Mixed Infection with AErogenes Capsulatus and Proteus Vulgaris. PMID- 17861213 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , May 28, 1902: Stated Meeting. PMID- 17861214 TI - INDEX TO SURGICAL PROGRESS. PMID- 17861215 TI - I. The Pathogenesis and Pathological Anatomy of Enlarged Prostate. PMID- 17861216 TI - II. Removal of an Upholsterer's Tack from the Right Bronchus. PMID- 17861217 TI - III. Landmarks in the Ureter. PMID- 17861218 TI - IV. Subcutaneous Rupture of the Kidney: With a Report of Nine Cases. PMID- 17861219 TI - V. Traumatic Rupture of the Spleen. PMID- 17861220 TI - VI. The Transduodenal Route (Duodeno-choledochotomy) in Cases of Impaction of Gall-Stones in the Lower Portion of the Common Duct: With Report of a Case of Choledochotomia Transduodenalis with Choledochoduodenostomia Interna. PMID- 17861221 TI - VII. Strangulation of Vermiform Appendix in Right Femoral Ring. PMID- 17861222 TI - VIII. Contribution to the Study of Intra-abdominal Omental Torsion. PMID- 17861223 TI - IX. Primary Tuberculosis of the Parotid Gland. PMID- 17861225 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 8, 1902: Stated Meeting. PMID- 17861224 TI - X. A Simple Device for Holding Ligatures. PMID- 17861226 TI - INDEX TO SURGICAL PROGRESS. PMID- 17861227 TI - I. Subdural Interposition of Rubber Tissue without Removal of the Gasserian Ganglion in Operations for Tic Douloureux. PMID- 17861228 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , October 6, 1902: Stated Meeting. PMID- 17861230 TI - INDEX TO SURGICAL PROGRESS. PMID- 17861229 TI - Moynihan on Retroperitoneal Hernia. PMID- 17861231 TI - III. Ureter-Catheterism: Its Purposes and Practicability: With the Presentation of a Ureter-Cystoscope for Male and Female. PMID- 17861232 TI - IV. On a Possible Cause of Difficulty in the Differential Diagnosis between Renal Calculi and Hepatic Calculi. PMID- 17861233 TI - V. Some Points in Ligation of Arteries. PMID- 17861234 TI - VI. A Case of Tuberculosis, Resembling Carcinoma, in the Tongue of an Old Man. PMID- 17861235 TI - VII. Persistent Thyrolingual Duct: Complete Branchial Fistula: With Note on the Teaching of Embryology by Means of Clay Models. PMID- 17861236 TI - VIII. Cysts in Connection with the Teeth. PMID- 17861237 TI - IX. Excision of the Clavicle. PMID- 17861238 TI - X. Osteoma of the Knee-Joint. PMID- 17861240 TI - II. Considerations Relative to Basedow's Disease: The Application of "Regionary Anaesthesia" in its Surgical Treatment. PMID- 17861239 TI - XI. Posterior Dislocation of the Head of the Tibia: With the Report of Three Cases. PMID- 17861241 TI - XII. An Apparatus to Facilitate the Application of Plaster Jackets during Spinal Hyperextension. PMID- 17861242 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 22, 1902: Stated Meeting. PMID- 17861243 TI - I. An Operation for the Radical Cure of Aneurism based upon Arteriorrhaphy. PMID- 17861244 TI - II. Cases Illustrating some Important Points in the Diagnosis and Treatment of Abdominal Contusions associated with Visceral Injuries. PMID- 17861246 TI - IV. A Case of Pancreatic Cyst, with Remarks on the Pathology and Surgical Treatment. PMID- 17861245 TI - III. Intraperitoneal Rupture of the Bladder: With Report of Two Recent Cases of Recovery after Suture. PMID- 17861247 TI - V. The Question of Surgical Intervention in Cases of Injuries to the Spine. PMID- 17861248 TI - VI. Post-Typhoidal Infection of Ribs. PMID- 17861249 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , November 12, 1902: Stated Meeting. PMID- 17861250 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , November 3, 1902: Stated Meeting. PMID- 17861251 TI - Intramediastinal Bronchotomy and OEsophagotomy. PMID- 17861252 TI - I. Neurofibromatosis of the Nerves of the Tongue (Macroglossia Neurofibromatosa) and of Certain Other Nerves of the Head and Neck. PMID- 17861254 TI - III. Extradural Haemorrhage from Rupture of the Middle Meningeal Artery. PMID- 17861253 TI - II. Report of Sixty Cases of Actinomycosis. PMID- 17861255 TI - IV. New Instruments for the Treatment of OEsophageal Stricture. PMID- 17861257 TI - VI. Acute Yellow Atrophy of the Liver as a Sequela to Appendectomy. PMID- 17861256 TI - V. Knife-blade Removed from Lung. PMID- 17861258 TI - VII. Primary Retroperitoneal Solid Tumors: With Report of a Case. PMID- 17861259 TI - VIII. Closure by Suture of Intestinal Perforations complicating Typhoid Fever: Report of Three Cases. PMID- 17861260 TI - XI. Note on the Frequent Great Disparity between Falls upon the Buttocks and the Subsequent Persistent Pain and Irremediable Helplessness in Persons in Advanced Years. PMID- 17861261 TI - X. Hygroma and Fibroma of the Tuber Ischii Bursae. PMID- 17861262 TI - XI. Blank-cartridge Wound infected with Tetanus Bacilli; Prompt Excision; no Tetanus. PMID- 17861263 TI - XII. Dislocation of Individual Carpal Bones, with Report of a Case of Luxation of the Scaphoid and Semilunar. PMID- 17861264 TI - XIII. The Treatment of Infantile Spastic Paralysis. PMID- 17861265 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , November 26, 1902: Stated Meeting. PMID- 17861266 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , December 10, 1902: Stated Meeting. PMID- 17861267 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , November 3, 1902: Stated Meeting. PMID- 17861268 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , December 1, 1902: Stated Meeting. PMID- 17861269 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , December 1, 1902: Stated Meeting. PMID- 17861270 TI - I. Splenopexy for Wandering Spleen: With Report of a Case. PMID- 17861271 TI - II. Urethroplasty: Remarks on the Repair of Defects of the Male Urethra, with Report of Two Cases. PMID- 17861272 TI - III. Carcinomatous Changes in an Area of Chronic Ulceration, or Marjolin's Ulcer. PMID- 17861273 TI - IV. A Case of Dislocation of the Hip in Acute Rheumatism. PMID- 17861274 TI - V. Instrument to Protect the Brain while doing Craniotomy with Gigli Saw. PMID- 17861275 TI - VI. Primary Tuberculosis of the Breast: A Report of a Recent Case, with a Review of the Literature of the Subject. PMID- 17861276 TI - VII. The Diagnosis of Intestinal Injury following Abdominal Contusion. PMID- 17861277 TI - VIII. Hepatic Duct Stones: With Report of a Recent Operated Case. PMID- 17861278 TI - IX. Primary Carcinoma of the Vermiform Appendix, with a Report of Three Cases. PMID- 17861280 TI - XI. Results of Decapsulation of the Kidney: A Study of Changes Noted in the Renal and Perirenal Tissues of Dogs after Decapsulation. PMID- 17861279 TI - X. The Surgical Treatment of Anuria. PMID- 17861281 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , January 14, 1903: Stated Meeting. PMID- 17861283 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , January 5, 1903: Stated Meeting. PMID- 17861282 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , January 5, 1903: Stated Meeting. PMID- 17861284 TI - I. The Surgical Treatment of Facial Paralysis by Nerve Anastomosis: With the Report of a Successful Case. PMID- 17861285 TI - II. On the Possibility of Operative Relief of Certain Forms of Facial Paralysis: With Report of a Case. PMID- 17861286 TI - III. Intracranial Neurectomy: Report of a Case Followed by Extensive Temporary Paralysis. PMID- 17861288 TI - V. Contribution to the Subject of Perineal Prostatectomy. PMID- 17861287 TI - IV. The Surgery of the Lower Ureter. PMID- 17861289 TI - VI. Ruptured Crucial Ligaments and their Repair by Operation. PMID- 17861290 TI - VII. A Case of End-to-End Anastomosis of the Popliteal Artery for Gunshot Injury. PMID- 17861291 TI - VIII. The Successful Removal of a Large Enchondroma of the Chest Wall, involving the Diaphragm. PMID- 17861292 TI - IX. Hepatic Syphilis from a Surgical Standpoint. PMID- 17861293 TI - X. Chronic Interlobular Pancreatitis: Report of a Case of Pancreatic Calculi, with Multiple Cysts of the Pancreas. PMID- 17861294 TI - XI. Tuberculosis of the Femoral, Inguinal, and Iliac Lymph Nodes secondary to Foot Wounds. PMID- 17861295 TI - XII. Contribution to the Literature of Old Irreducible Dislocations of the Shoulder-Joint. PMID- 17861296 TI - XIII. An Os Trigonum detected by the Rontgen Rays. PMID- 17861297 TI - XIV. An Aspirating Trocar. PMID- 17861298 TI - XV. A New Osteoplastic Trephine. PMID- 17861299 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , January 28, 1903: Stated Meeting. PMID- 17861300 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , February 2, 1903: Stated Meeting. PMID- 17861301 TI - Exclusion of Actinic Rays of Light during Operation for General Peritonitis. PMID- 17861302 TI - A Test as to Whether the Cathelin Urine Divisor forms a Perfect Septum in the Bladder or Not. PMID- 17861303 TI - I. Results of One Thousand Operations for the Radical Cure of Inguinal and Femoral Hernia. PMID- 17861304 TI - II. Myositis Ossificans with a Report of Two Cases,-One Traumatic, the other Non traumatic. PMID- 17861306 TI - IV. Gunshot Wound of the Longitudinal Sinus Recovery with Hemianopsia after Trephining. PMID- 17861305 TI - III. On the Pathology of So-called Bone Aneurisms. PMID- 17861307 TI - V. The Orbital Route for Removal of the Second Branch of the Fifth Nerve at the Foramen Rotundum. PMID- 17861308 TI - VI. I. Tubage of the Pharynx for facilitating the Administration of Anaesthetics and Preventing the Inhalation of Blood in Certain Operations on the Mouth and Face. II. A Hot-Water Bed for the Operating Table. PMID- 17861309 TI - VII. The Drowning of Patients in Faecal Vomit during Operations for Intestinal Obstruction and Septic Peritonitis. PMID- 17861310 TI - VIII. Splenic Infections with Reports of Two Cases recovering after Operation. PMID- 17861311 TI - IX. Primary Typhoidal Perforation of the Gall-Bladder. PMID- 17861312 TI - X. Retroperitoneal Hernia. Acute Strangulation of a Knuckle of Ileum in a Pericaecal Pouch. PMID- 17861313 TI - XI. A Suction Apparatus for Continuous Drainage, with Report of Case of Intraperitoneal Rupture of Bladder. PMID- 17861314 TI - XII. Primary Carcinoma of the Appendix. PMID- 17861315 TI - XIII. Excision of the Scapula for Progressive Chronic Interstitial Myositis associated with Obliterating Endarteritis. PMID- 17861316 TI - XIV. Instruments for Use through Cylindrical Rectal Specula, with the Patient in the Knee-Chest Posture. PMID- 17861317 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , February 11, 1903: Stated Meeting. PMID- 17861318 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, February 25, 1903. PMID- 17861319 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , March 2, 1903: Stated Meeting. PMID- 17861320 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , March 2, 1903: Stated Meeting. PMID- 17861322 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , March 25, 1903: Stated Meeting. PMID- 17861321 TI - I. Surgery of the Pancreas With Especial Consideration of Trauma and Inflammatory Processes. PMID- 17861324 TI - INDEX TO SURGICAL PROGRESS. PMID- 17861323 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , April 6, 1903: Stated Meeting. PMID- 17861325 TI - II. A Review of Three Hundred and Three Operations upon the Stomach and First Portion of the Duodenum With Tabulated Report of Three Hundred and Thirteen Operated Cases. PMID- 17861326 TI - III. An Improved Filigree for the Repair of Large Defects in the Abdominal Wall. PMID- 17861327 TI - IV. Three Successful Laparotomies for Intestinal Perforation in Typhoid Fever. PMID- 17861328 TI - V. The Surgical Features of Perforation of the Intestine in Typhoid Fever in Children. PMID- 17861330 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , March 11, 1903: Stated Meeting. PMID- 17861329 TI - VI. Dislocation of the Carpal Scaphoid. PMID- 17861331 TI - I. Thyroidectomy and Sympathectomy for Exophthalmic Goitre. PMID- 17861332 TI - II. The Surgical Treatment of Exophthalmic Goitre. PMID- 17861333 TI - III. Bilateral Bony Ankylosis of the Temporomaxillary Articulation of Traumatic Origin and its Surgical Treatment. With Report and Presentation of Two Cases recently treated by Operation. PMID- 17861335 TI - V. The Gradual Surgical Occlusion of Large Arteries: Its Relative Advantages together with an Experimental Inquiry as to its Feasibility. PMID- 17861334 TI - IV. The Anatomy of the Inferior Ethmoidal Turbinate Bone with Particular Reference to Cell Formation; Surgical Importance of such Ethmoid Cells. PMID- 17861336 TI - VI. The Treatment of the Peritoneum in Diffuse Peritonitis. PMID- 17861337 TI - VII. A Proposed Method of Retroduodenal Choledochotomy for the Removal of Impacted Calculi in the Retroduodenal and Papillary Portions of the Common Bile Duct. PMID- 17861338 TI - VIII. A Chemical Hypothesis for the Etiology of Cancer. PMID- 17861339 TI - IX. The Method of Infection of Actinomycosis in Man With a Report of Five Cases. PMID- 17861340 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , April 8, 1903: Stated Meeting. PMID- 17861341 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , April 6, 1903: Stated Meeting. PMID- 17861343 TI - II. Cystic Degeneration of the Mamma showing Transformation into Scirrhous Carcinoma. PMID- 17861342 TI - I. Operative Possibilities in Cases of Advanced Carcinoma of the Breast. PMID- 17861344 TI - III. Surgical Treatment of Cholelithiasis: A Report of the Operations for Cholelithiasis, in the Service of Dr. A. G. Gerster, at Mount Sinai Hospital, During the Five Years, 1898-1902. PMID- 17861345 TI - IV. A Prostatic Tractor for Perineal Prostatectomy. PMID- 17861346 TI - V. A Case of Ascites due to Liver Cirrhosis treated by Operation. PMID- 17861347 TI - VI. Gangrene of Colon and Ileum after Operation for Appendicitis. PMID- 17861349 TI - VIII. Embolic Gangrene of the Leg as a Sequel of Acute Lobar Pneumonia. PMID- 17861348 TI - VII. Paraffin Casts of Ureteral Calyces, Pelves, and Ureters. PMID- 17861351 TI - X. Dislocation of the Outer End of the Clavicle: With Report of Four Cases. PMID- 17861350 TI - IX. Fractures of the Vertebrae. PMID- 17861352 TI - XI. Method of retaining Ends of Fractured Bones in Apposition during Fixation by Plaster-of-Paris Dressing, etc. PMID- 17861353 TI - XII. Blood Examinations in their Relation to Surgical Procedures. PMID- 17861354 TI - XIII. Myositis Ossificans Traumatica. PMID- 17861355 TI - XIV. Bridge for Treatment of Nasal Fractures and Deformities. PMID- 17861356 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , April 22, 1903: Stated Meeting. PMID- 17861357 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , May 13, 1903: Stated Meeting. PMID- 17861358 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , June 1, 1903: Stated Meeting. PMID- 17861359 TI - An Aid to the Localization, by X-Rays, of Foreign Bodies embedded in the Tissues. PMID- 17861360 TI - The Exposure of the Postduodenal Portion of the Common Bile Duct. PMID- 17861361 TI - I. A Case of Malignant OEdema. PMID- 17861362 TI - II. Fatal Haemorrhage from Trephining. PMID- 17861363 TI - III. Notes on a Case of Fusiform Aneurism treated by Matas's Method. PMID- 17861365 TI - V. The Treatment of Aneurism of the External Iliac Artery by Digital Compression. With Report of a Case. PMID- 17861364 TI - IV. On an Extraordinary Case of Aneurisma Racemosum: Presented to the Surgical Section of the New York Academy of Medicine, March 13, 1903. PMID- 17861366 TI - VI. Calculous Anuria: Its Diagnosis and Treatment. PMID- 17861367 TI - VII. A New Method of Performing Perineal Section without a Guide. PMID- 17861368 TI - VIII. A Clinical Contribution to the Knowledge of Tubercular Diseases of the Female Urinary Tract With a Report of Seven Complete Nephro-Ureterectomies. PMID- 17861369 TI - IX. Contribution to the Surgery of Pyosalpinx. PMID- 17861370 TI - X. Congenital Luxation of the Ankle. PMID- 17861371 TI - XI. The Treatment of the Complications attendant upon Chronic Gall-Stone Disease. PMID- 17861372 TI - XII. Tropical Abscess of the Liver: A Report of Military Experience in the Philippines. PMID- 17861373 TI - XIII. Intestinal Localization: A Study on the Cadaver for the Purpose of Determining to What Extent the Various Parts of the Small Intestine may be Identified Through an Abdominal Wound. PMID- 17861375 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , May 27, 1903: Stated Meeting. PMID- 17861374 TI - XIV. A Further Case of "Hour-Glass" Stomach. PMID- 17861376 TI - Hernia of the Urinary Bladder. PMID- 17861377 TI - The Exposure of the Postduodenal Portion of the Common Bile Duct. PMID- 17861378 TI - I. The Surgical Problem in Prostatic Hypertrophy. PMID- 17861379 TI - II. On the Treatment of Fracture of the Mandible: With Method of Wiring. PMID- 17861381 TI - IV. Report of a Case of Recurrent Dislocation of the Ulnar Nerve cured by Operation: With Summary of Previously Reported Cases. PMID- 17861380 TI - III. Traumatic Aneurism of the Left Subclavian Artery produced by Fracture of the Clavicle. PMID- 17861382 TI - V. One Thousand Abdominal Closures by a New Method, without a Known Hernia. PMID- 17861383 TI - VI. Splenectomy for Banti's Disease: Followed by Thrombosis of the Right Internal Jugular, Subclavian, and Innominate Veins. Recovery. PMID- 17861384 TI - VII. On the Pathology and Classification of Intussusceptions, with a Resume of those Arising from the Appendix Caeci. PMID- 17861385 TI - VIII. The Diagnosis and Treatment of Acute Pancreatitis. PMID- 17861386 TI - IX. Idiopathic Dilatation of the Colon. PMID- 17861387 TI - X. A Contribution to the Study of Intestinal Suture, with a New Method of Intestinal Union. PMID- 17861388 TI - INDEX TO SURGICAL PROGRESS. PMID- 17861389 TI - I. Method of Suturing the Prolapsed Kidney. PMID- 17861390 TI - II. The Gauze-bearing Tape and the Gravity Pad in Pelvic and Abdominal Surgery; Improvements in Technique. PMID- 17861391 TI - III. Traumatic Epilepsy Report of a Case improved by Trephining and Insertion of a Celluloid Plate beneath the Skull. PMID- 17861392 TI - IV. On the Results obtainable by Operative Measures in Affections of the Stomach. PMID- 17861393 TI - V. Intestinal Obstruction following Operation for Reducible Left Inguinal Hernia due to a Loop of Small Intestine caught in Treitz's Fossa. PMID- 17861395 TI - VII. Local Anaesthesia. PMID- 17861394 TI - VI. Perforating Gunshot Wound of the Cervical Portion of the Spinal Cord. Report of a Case in which Recovery was secured, with Ability to Walk. PMID- 17861396 TI - VIII. An Experimental Research into the Temperature Relationship existing in Shock. PMID- 17861398 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , June 1, 1903: Stated Meeting. PMID- 17861397 TI - IX. Anomalies in the Circle of Willis. With the Report of a Case in which the communicating Arteries were absent. PMID- 17861399 TI - INDEX TO SURGICAL PROGRESS. PMID- 17861400 TI - I. On Removal, after Suprapubic Cystotomy, of the Prostate and of the Prostatic Urethra for Senile Enlargement of the Prostate. With a List of Twelve Cases. PMID- 17861401 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 14, 1903: Stated Meeting. PMID- 17861402 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , October 5, 1903: Stated Meeting. PMID- 17861403 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , November 2, 1903: Stated Meeting. PMID- 17861404 TI - III. The Mixed Tumors of the Salivary Glands. PMID- 17861405 TI - II. Intestinal Perforation in Typhoid Fever. PMID- 17861406 TI - IV. Excision of Tuberculous Mass from Liver. PMID- 17861407 TI - I. Treatment by Direct Dilatation of Cicatricial OEsophageal Stricture. PMID- 17861408 TI - II. Diverticula of the OEsophagus, with the Report of a Case. PMID- 17861410 TI - IV. The Mixed Tumors of the Salivary Glands. PMID- 17861409 TI - III. On Bronchoscopy with Report of a Case in which a Foreign Body was removed from the Right Lower Lobe of a Lung through a Bronchoscope. PMID- 17861411 TI - V. Operative Removal of a Tumor of the Liver Report of a Case of Resection of the Liver for Gumma; Cholecystectomy. PMID- 17861412 TI - VI. The Aponeuroses the Supporting Structures of the Abdominal Wall; their Approximation for the Prevention and Cure of Hernia. PMID- 17861413 TI - VII. Fibrinous Vesical Concretions. Report of a Case in which Two Large Fibrinous Concretions were removed from the Urinary Bladder. PMID- 17861414 TI - VIII. Partial Enterocele. PMID- 17861416 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 28, 1903: Stated Meeting. PMID- 17861415 TI - IX. Perforation of the Urinary Bladder by an Appendiceal Abscess. PMID- 17861417 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , November 11, 1903: Stated Meeting. PMID- 17861418 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , May 11, 1903: Stated Meeting. PMID- 17861419 TI - Blood-Pressure in Surgery and the Treatment of Surgical Shock. PMID- 17861420 TI - I. Radical Operations for the Cure of Cancer of the Pyloric End of the Stomach. PMID- 17861421 TI - II. Contribution to the Surgery of Perforating Gastric Ulcer. PMID- 17861423 TI - IV. On the Treatment of Penetrating Wounds of the Abdomen With Report of Sixteen Cases. PMID- 17861422 TI - III. Cirrhosis of the Stomach. PMID- 17861424 TI - V. Unilateral Haematuria from Chronic Nephritis. Recovery after Decapsulation of Kidney. PMID- 17861425 TI - VI. Primary Carcinoma of the Bulbous Urethra. A Statistical Digest, with some Unrecorded Cases. PMID- 17861426 TI - VII. Complications and Sequels of Prostatectomy. PMID- 17861427 TI - VIII. A Case of Enormous Prostatic Calculus: Secondary to Traumatic Stricture of the Perineal Urethra; Suppuration About the Stone; Secondary Abscess in the Pelvis; Extensive Urethrorectal Fistula Following Perineal Section for the Calculus; Perineal Rectoplasty for the Closure of the Fistula; Recovery. PMID- 17861429 TI - X. On Costal and Thoracic Resection for Pyothorax With Special Reference to the Exploratory Method. PMID- 17861428 TI - IX. Fibromata of the Tunica Vaginalis. PMID- 17861430 TI - XI. The Treatment of Pulsating Exophthalmos. PMID- 17861432 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , November 25, 1903: Stated Meeting. PMID- 17861431 TI - XII. Lip-Tie. PMID- 17861433 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , November 2, 1903: Stated Meeting. PMID- 17861434 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , December 7, 1903: Stated Meeting. PMID- 17861435 TI - I. Traumatic Asphyxia. Report of a Recent Case, with a Study of the Minute Pathology, and Summary of Reported Cases. PMID- 17861436 TI - II. Operation in Spinal-Cord Injuries. PMID- 17861437 TI - III. On the Present Status of the Operation of Gastro-Enterostomy. PMID- 17861439 TI - V. Spontaneous Gangrene of the Hollow Viscera A Study of Mesenteric Occlusion. PMID- 17861438 TI - IV. Gastric Dilatation and Tetany. PMID- 17861440 TI - VI. Chronic Empyema of the Gall-Bladder. Report of a Case of Thirteen or More Years' Duration. PMID- 17861441 TI - VII. Traumatic Pyeloparanephric Cyst. PMID- 17861442 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , December 9, 1903: Stated Meeting. PMID- 17861443 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , December 23, 1903: Stated Meeting. PMID- 17861444 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , December 7, 1903: Stated Meeting. PMID- 17861445 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. with the Chicago Medical Society, held January 13, 1904: Joint Meeting. PMID- 17861446 TI - I. Lymphatic Constitution. Care of the Lymphatics during and after Surgical Operations. PMID- 17861447 TI - II. Pulsating Exophthalmos due to Traumatic Aneurism of the Internal Carotid Artery: Report of a Case Caused by a Bullet Wound of the Base of the Skull. PMID- 17861448 TI - III. Rhinophyma: Report of a Case, with Operation for its Relief. PMID- 17861449 TI - IV. Sialolithiasis. PMID- 17861450 TI - V. Stricture of the OEsophagus due to Typhoid Ulceration. PMID- 17861451 TI - VI. One Hundred Cases of Gastro-Enterostomy for Simple Ulcer of the Stomach and Duodenum. PMID- 17861453 TI - VIII. The Diagnosis of Abscess of the Liver. PMID- 17861452 TI - VII. Postoperative Pneumonia, with Experiments upon its Pathogeny. PMID- 17861455 TI - X. Intestinal Obstruction due to Fibrous Stricture consequent upon Strangulated Hernia: With an Account of Three New Cases. PMID- 17861454 TI - IX. The Treatment of Posterior Perforations of the Fixed Portions of the Duodenum. PMID- 17861456 TI - XI. Papilloma of the Renal Pelvis with Massive Hydronephrosis. PMID- 17861457 TI - XII. The Rontgen-Ray Diagnosis of Renal Calculus. PMID- 17861458 TI - XIII. Ureterocystostomy for Accidental Wound of the Ureter in Vaginal Hysterectomy. PMID- 17861459 TI - XIV. Injuries to the Axillary Vessels occurring during Operations for Carcinoma of the Breast. PMID- 17861460 TI - XV. Arteriovenous Aneurisms: A Case of Traumatic Arteriovenous Aneurism of the Common Femoral Artery and Vein-Unsuccessfully Treated by a New Method of Compression-and Finally Cured by the Proximal Ligation of the External Iliac Artery Extraperitoneally-with the Suggestion of the Application to these Aneurisms of the Matas Method of Operation Used for Ordinary Aneurisms-and the Mention of Some Other Recent Methods of Operating. PMID- 17861461 TI - XVI. Skin-Grafting Infected Areas. PMID- 17861462 TI - XVII. Treatment of Fractures. PMID- 17861464 TI - XIX. Some Observations on the Effects produced on the Skin by the Discharge of Small-Arms loaded with Smokeless Powders. PMID- 17861463 TI - XVIII. A New Osteoplastic Amputation at the Ankle-Joint. PMID- 17861465 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , January 13, 1904: Stated Meeting. PMID- 17861466 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , January 4, 1904: Stated Meeting. PMID- 17861467 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , February 1, 1904: Stated Meeting. PMID- 17861468 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , February 10, 1904: Stated Meeting. PMID- 17861469 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , February 1, 1904: Stated Meeting. PMID- 17861470 TI - I. The Operative Treatment of the Hypertrophied Prostate. With Special Reference to its Evolution, Present Status, and the Choice of Operative Method and Technique. PMID- 17861471 TI - II. Primary Carcinoma of the Prostate. PMID- 17861472 TI - III. Revival of Suprapubic Prostatectomy. PMID- 17861473 TI - IV. Intradural Tumor of the Cervical Meninges. With Early Restoration of Function in the Cord after Removal of the Tumor. PMID- 17861474 TI - V. Sarcoma of the Tongue. Report of a Recent Case, with Analysis of Previously Recorded Cases. PMID- 17861475 TI - VI. Malignant Disease of the Larynx; Total Laryngectomy. PMID- 17861477 TI - VIII. Extensive Subcutaneous Laceration of the Abdominal Muscles. PMID- 17861476 TI - VII. A Self-Retaining Abdominal Retractor. PMID- 17861478 TI - IX. Remarks on the Radical Cure of Femoral Hernia. PMID- 17861480 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , January 27, 1904: Stated Meeting. PMID- 17861479 TI - X. Experimental Surgery. Working Plans of a Sanitary Animal Cage for Laboratory Use. PMID- 17861481 TI - I. The Anatomy and Surgery of the Internal Derangements of the Knee-Joint. Based on a Study of 150 Dissected Joints and the Literature. PMID- 17861482 TI - VI. Suture of the Brachial Artery. PMID- 17861483 TI - VII. Pyaemic Glanders in the Human Subject. Report of a Recent Case of Laboratory Origin terminating in Recovery. PMID- 17861484 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , February 24, 1904: Stated Meeting. PMID- 17861485 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , March 9, 1904: Stated Meeting. PMID- 17861487 TI - Certain Points in Suprapubic Prostatectomy. PMID- 17861486 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , March 7, 1904: Stated Meeting. PMID- 17861488 TI - Value of Peroxide of Hydrogen. PMID- 17861489 TI - II. Some Remarks on Tumors of the Chiasm, With a Proposal how to reach the Same by Operation. PMID- 17861490 TI - III. Primary Cholecystectomy: Scope, Method, and Results Conclusions from Forty two Cases in the Practice of the Author. PMID- 17861491 TI - IV. Primary Sarcoma of the Spleen, and Its Treatment by Splenectomy. PMID- 17861492 TI - V. Hernia of the Uterus through the Inguinal Canal. PMID- 17861493 TI - I. Observations on the Results in 125 Cases of Sarcoma. PMID- 17861494 TI - II. The Combined Transverse and Longitudinal Incision in Laparotomy. PMID- 17861495 TI - III. Peptic Ulcer of the Jejunum. PMID- 17861496 TI - IV. The Treatment of Postoperative Vomiting by Gastric Lavage. PMID- 17861497 TI - V. Primary Spasm and Hypertrophy of the Pyloric Sphincter, and Resultant Enormous Dilatation of the Stomach: Relief by Pyloroplasty and Gastroplication. PMID- 17861498 TI - VI. Congenital and Infantile Omentocele on same Side, Separated from Greater Omentum and Peritoneal Cavity. PMID- 17861499 TI - VII. Unsuspected Lesions in Movable Kidneys Discovered during Nephropexy. PMID- 17861500 TI - VIII. Transverse Ectopy of the Testis. PMID- 17861501 TI - IX. Osteomalacia in the Male. PMID- 17861502 TI - X. Physiological Salt Solution. PMID- 17861503 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , March 23, 1904: Stated Meeting. PMID- 17861504 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , April 13, 1904: Stated Meeting. PMID- 17861505 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , April 4, 1904: Stated Meeting. PMID- 17861506 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , March 7, 1904: Stated Meeting. PMID- 17861507 TI - I. Contribution to the Surgery of Neurofibroma of the Acoustic Nerve: With Remarks on the Surgical Procedure. PMID- 17861508 TI - II. Adenoma of the Mucous Glands of the Lips as a Cause of Macrocheilia. PMID- 17861509 TI - III. Lingual Goitre: Accessory Thyroids at the Base of the Tongue. PMID- 17861510 TI - IV. Purulent Mastoiditis: Sinus Thrombosis; Threatened Cerebral Abscess; Recovery After Operation. PMID- 17861511 TI - V. On the Use of an Electro-Magnet for Removal of a Foreign Body from a Bronchus. PMID- 17861512 TI - VI. Removal by Gastrotomy of a Hatpin swallowed by a Twenty Months' Old Child. PMID- 17861513 TI - VII. Details of the Technique of a Posterior Gastro-Enterostomy. PMID- 17861514 TI - VIII. Gangrene of the Hollow Viscera: A Report of Three Cases, with Illustration. PMID- 17861515 TI - IX. Results in Abdominal Wall Suture. PMID- 17861516 TI - X. A Posterior Incision in Certain Appendicitis Operations. PMID- 17861517 TI - XI. Inflamed Appendix in the Sac of a Femoral Hernia. PMID- 17861518 TI - XII. A Radical Operation for Malignant Neoplasm of the Urinary Bladder. PMID- 17861519 TI - XIII. Repair of the Urethra by Transplantation of the Urethra of Animals. PMID- 17861520 TI - XIV. The Formation of an Artificial Vagina by Intestinal Trransplantation. PMID- 17861521 TI - XV. The Use of Electricity in Skin-Grafting. PMID- 17861522 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , April 27, 1904: Stated Meeting. PMID- 17861524 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , April 4, 1904: Stated Meeting. PMID- 17861523 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , May 2, 1904: Stated Meeting. PMID- 17861525 TI - I. Aseptic Surgical Technique: Minimum Requirements for Aseptic Surgical Operating in a Hospital in which the Personnel of the Operating Room is Permanent. PMID- 17861526 TI - II. Aseptic Surgical Technique: What are the Minimum Requirements for Aseptic Surgical Operations in Hospitals where the Surgeon is Assisted by a Large Staff of Internes and by Nurses from a Training-School? PMID- 17861527 TI - III. Some Studies in Asepsis. PMID- 17861528 TI - IV. An Adenoma of Sebaceous Glands of the Abdominal Wall: With a Review of the Literature of Adenoma and Hyperplasia of the Sebaceous Glands. PMID- 17861529 TI - V. The Treatment of Haematemesis by Gastro-Enterostomy: With Report of Case. PMID- 17861530 TI - VI. Postoperative Intestinal Obstruction: With a Report of Three Cases. PMID- 17861531 TI - VII. Mesosigmoiditis, and its Relations to Recurrent Volvulus of the Sigmoid Flexure. PMID- 17861532 TI - VIII. Meckel's Diverticulum: With Report of Strangulated Inguinal Hernia of Same. PMID- 17861533 TI - IX. Contribution to the Surgery of the Deep Urethra: I. Primary Urethral Anastomosis After Lacerated Wound of the Perineal Urethra. II. Urethral Fistula, Sequel to Prostatectomy. PMID- 17861534 TI - X. The Union of Ununited Fractures of the Neck of the Femur by Open Operation. PMID- 17861536 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , May 11, 1904: Stated Meeting. PMID- 17861535 TI - XI. The Treatment of Fracture of Patella: With Report of Results After Arthrotomy and Suture. PMID- 17861537 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , May 2, 1904: Stated Meeting. PMID- 17861538 TI - On the Value of Postoperative Gastric Lavage. PMID- 17861539 TI - I. Bacillus Pyocyaneus Septicaemia associated with Blastomycetic Growth in Primary Wound. PMID- 17861540 TI - II. The Bridging of Nerve Defects: A Contribution to the Surgery of Nerves. PMID- 17861541 TI - III. Total Avulsion of the Scalp. PMID- 17861542 TI - IV. Traumatic Abscess of Cerebrum: Recovery After Trephining and Drainage. PMID- 17861543 TI - V. Fracture of the Base of the Skull: A Contribution Based on the Clinical and Pathological Records of Fifty Cases. PMID- 17861544 TI - VI. Ligation of Both Common Carotid Arteries: Report of a Case in which the Right Common Carotid Artery was Ligated for Inoperable Sarcoma, with Temporary Improvement; Ligation of the Left Common Carotid Sixty-Nine Days After the First Operation. PMID- 17861545 TI - VII. Penetrating Wounds of the Chest, Perforating the Diaphragm, and Involving the Abdominal Viscera: Case of Successful Spleen Suture for Traumatic Haemorrhage. PMID- 17861546 TI - VIII. Operative Treatment of Perforating Gastric Ulcer: Report of a Third Consecutive Successful Case of Suture. PMID- 17861547 TI - IX. A New Operation for Intestinal Stenoses. PMID- 17861548 TI - X. Pneumococcus Peritonitis: A Report of Five Cases. PMID- 17861549 TI - XI. The Treatment of the Stump in Appendicectomy: Based on a Pathologic and Bacteriologic Study of the Appendix. PMID- 17861550 TI - XII. Appendix Vermiformis concealed in the Postcaecal Retroperitoneal Space. PMID- 17861551 TI - XIII. Remarks on Appendicitis: Based on an Analysis of 219 Cases Operated Upon at Lebanon Hospital up to April 1, 1904. PMID- 17861553 TI - XV. Fracture of the Tibial Tubercle. PMID- 17861552 TI - XIV. Double Traumatic Iliac Dislocation of the Hip: Report of a Recent Case, with a Review of the Literature of the Subject. PMID- 17861554 TI - XVI. Abdominal Crises caused by Meckel's Diverticulum: Report of Two Recent Cases, with a Review of the Literature of the Subject. PMID- 17861556 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , May 25, 1904: Stated Meeting. PMID- 17861555 TI - XVII. The Use of the Segmented Ring in Gastric and Intestinal Anastomoses: A Clinical and Experimental Study. PMID- 17861557 TI - XVII. I. Hypernephroma of Kidney II. Fibro-Adenoma of Inner Wall of Ileum: A Clinical Report. PMID- 17861558 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 26, 1904: Stated Meeting. PMID- 17861559 TI - The Annals of Surgery, 1885-1904. PMID- 17861560 TI - I. On the Morphology of Carcinoma and the Parasitic Theory of its Etiology. PMID- 17861561 TI - II. The Present Position of the Surgery of the Hypertrophied Prostate. PMID- 17861562 TI - III. Intussusception of Meckel's Diverticulum: Report of a Case Complicated by Stenosis of the Intestine Below Leading to Secondary Intussusception of the Small Intestine. PMID- 17861563 TI - IV. The Operative Treatment of Cancer of the Breast: With an Analysis of a Series of One Hundred Consecutive Cases. PMID- 17861564 TI - V. Modern Bullet Wounds. PMID- 17861566 TI - VII. Birth-Fracture of the Skull: Family of Three, Illustrating the Effects of Operative Treatment. PMID- 17861565 TI - VI. Some Experiments with a New Method of Closing Wounds of the Larger Arteries. PMID- 17861567 TI - VIII. Divulsion in OEsophageal Strictures by Means of a New Instrument. PMID- 17861568 TI - IX. Parotitis following Injury or Disease of the Abdominal and Pelvic Viscera. PMID- 17861569 TI - X. Duodenal Ulcer: A Clinical Review of Fifty-Eight Operated Cases, with Some Remarks on Gastrojejunostomy. PMID- 17861570 TI - XI. Tetany, and Foreign Bodies in the Stomach: Tetany Caused by a Mass in the Stomach, Composed of Forty Metallic Articles, Weighing One Pound; Gastrotomy; Cured. PMID- 17861572 TI - XIII. Hernia of the Bladder complicating Inguinal Hernia. PMID- 17861571 TI - XII. Intra-Abdominal Torsion of the Entire Great Omentum. PMID- 17861573 TI - XIV. Dermoid Cyst of the Pelvic Connective Tissue: Two Cases, with a Consideration of Twenty-Four Reported Cases. PMID- 17861574 TI - XV. The Iliac Extraperitoneal Operation for Stone in the Lower Ureter in the Male. PMID- 17861575 TI - XVI. Undescended Testicle: Based on a Study of Seventy-Seven Cases. PMID- 17861576 TI - I. An Adjustable Metallic Interdental Splint for the Treatment of Fracture of the Lower Jaw: With Report of Cases in which it has been Applied by the Author. PMID- 17861577 TI - XI. Dislocations of the Patella, with Rotation on its Horizontal Axis. PMID- 17861578 TI - XII. The Matas Operation for Aneurism: Report of a Case of Popliteal Aneurism so Treated. PMID- 17861579 TI - XIII. Loss of Entire Lower Lip: Repair by Flap from the Arm. PMID- 17861580 TI - XIV. A Regulable Combined Dropping and Pouring Device for the Administration of Anaesthetics. PMID- 17861582 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , November 9, 1904: Stated Meeting. PMID- 17861581 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 12, 1904: Stated Meeting. PMID- 17861583 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , October 3, 1904: Stated Meeting. PMID- 17861584 TI - The Operative Treatment of Cancer of the Breast. PMID- 17861585 TI - II. Some Considerations regarding Wounds of the Liver. PMID- 17861586 TI - III. Congenital Elongation of the Left Lobe of the Liver. PMID- 17861588 TI - V. Contribution to the Surgery of Gastric Ulcer. PMID- 17861587 TI - IV. The Surgical Treatment of Chronic Dyspepsia due to Defective Drainage, and Chronic Inflammation of the Stomach resulting from Gastric Atony and Dilatation. PMID- 17861589 TI - VI. Penetrating Wounds of the Abdomen: Report of Six Cases of Gunshot and Stab Wounds of the Abdomen. PMID- 17861590 TI - VII. Hepato-Cholangio-Jejunostomy: For Complete Cicatricial Obstruction of the Hepatic and Common Ducts. PMID- 17861591 TI - VIII. Volvulus of the Caecum: With an Account of Rare and Possibly Common Cases. PMID- 17861593 TI - X. Luys's Instrument for the Intravesical Separation of the Two Urines. PMID- 17861592 TI - IX. An Operation for Inguinal Hernia. PMID- 17861594 TI - I. Acid Intoxication: Its Significance in Surgical Conditions. PMID- 17861595 TI - II. Gall-Bladder and Biliary - Duct Surgery. PMID- 17861596 TI - III. Volvulus of the Jejunum. PMID- 17861597 TI - IV. Operations on the Lower Ends of the Ureters by the Inguinal Extraperitoneal Route under Local Anaesthesia (Cocaine): A Report of Three Ureterovesical Implantations and the Removal of a Ureteral Calculus. PMID- 17861599 TI - VI. Case of Bone Transference: Use of a Segment of Fibula to Supply a Defect in the Tibia. PMID- 17861598 TI - V. Primary Urethral Calculus: With Report of a Case. PMID- 17861600 TI - VII. Contrecoup Fracture of the Sternum. PMID- 17861601 TI - VIII. Fracture of the Carpal Scaphoid, with Habitual Dislocation of the Central Fragment. PMID- 17861602 TI - IX. Interscapulothoracic Amputation: Report of Operation for Sarcoma of the Humerus. PMID- 17861604 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , November 7, 1904: Stated Meeting. PMID- 17861603 TI - X. Symmetrical Inflammation of the Epiphyseal Beak of the Tibia. PMID- 17861605 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , November 7, 1904: Stated Meeting. PMID- 17861606 TI - I. The Diagnosis and Treatment of Fracture of the Carpal Scaphoid and Dislocation of the Semilunar Bone: With a Report of Thirty Cases. PMID- 17861607 TI - II. Fractures of the Tarsal Bones. PMID- 17861609 TI - IV. A Case of Cervical Rib with Symptoms resembling Subclavian Aneurism. PMID- 17861608 TI - III. Technique of Exposure of the Spinal Cord and Canal; Osteoplastic Resection and Laminectomy. PMID- 17861610 TI - V. Cases of Intussusception in Children treated by Laparotomy. PMID- 17861611 TI - VI. A Series of Cases of Intussusception in Childhood. PMID- 17861612 TI - VII. Interstitial Hernia. PMID- 17861613 TI - VIII. The Relation of Mechanical Distention to the Etiology of Appendicitis. PMID- 17861615 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , December 14, 1904: Stated Meeting. PMID- 17861614 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , November 23, 1904: Stated Meeting. PMID- 17861616 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , December 5, 1904: Stated Meeting. PMID- 17861617 TI - I. Studies on the Pathology and Etiology of Obstructive Hypertrophy and Atrophy of the Prostate Gland. PMID- 17861618 TI - II. Has the Catheter a Place in the Treatment of Chronic Prostatic Hypertrophy? PMID- 17861620 TI - IV. Some Anatomical Points connected with the Performance of Prostatectomy: With Remarks Upon the Operative Treatment of Prostatic Hypertrophy. PMID- 17861619 TI - III. Prostatism without Enlargement of the Prostate: Its Diagnosis and Treatment. PMID- 17861621 TI - V. The Question of Priority in the Adoption of the Method of Total Enucleation, Suprapubically, of the Hypertrophied Prostate. PMID- 17861623 TI - VII. Suprapubic Prostatectomy without Ether or Chloroform: By Use of Nitrous Oxide Gas Anaesthesia. PMID- 17861622 TI - VI. The Treatment of Prostatic Hypertrophy by Enucleation through a Suprapubic Incision. PMID- 17861624 TI - VIII. Conservative Perineal Prostatectomy: The Results of Two Years' Experience and Report of Seventy-Five Cases. PMID- 17861625 TI - IX. The Cause of Incontinence as a Sequel of Prostatectomy. PMID- 17861626 TI - X. The Choice of Operative Method for the Removal of the Hypertrophied Prostate. PMID- 17861627 TI - XI. A Study of Various Forms of Prostatic Hypertrophy from Post-Mortem Specimens and by the Cystoscope, with Reference to Operation. PMID- 17861628 TI - XII. Transperitoneal Ligature for Aneurism of External Iliac Artery. PMID- 17861629 TI - XIII. An Osteoma of the Frontal Sinus. PMID- 17861630 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , December 5, 1904: Stated Meeting. PMID- 17861631 TI - I. Actinomycosis. PMID- 17861633 TI - III. Retrosternal Accessory Thyroid Tumor: Report of a Case Requiring Removal, Terminating Fatally. PMID- 17861632 TI - II. Cerebral Tumor: Report of a Case of Removal in Two Stages by the Osteoplastic Method; Subsequent Wiring of Bone-Flap; Introduction of a Gold Plate. PMID- 17861634 TI - IV. Transthoracic Resection of the Lower End of the OEsophagus: Under Negative Air-Pressure in Sauerbruch's Box; A Personal Experience. PMID- 17861635 TI - V. Gastro-enterostomy and Pyloroplasty: An Experimental Study by Means of the Rontgen Rays. PMID- 17861636 TI - VI. Resection of the Middle Third of the Stomach for Carcinoma of the Greater Curvature: End-to-End Anastomosis; Recovery. PMID- 17861637 TI - VII. Some Surgical Considerations Pertaining to Gastric Dilatation. PMID- 17861638 TI - VIII. Gunshot Wound of the Pancreas: Report of Case, and Review of Literature. PMID- 17861639 TI - IX. Hydrocele in the Female. PMID- 17861640 TI - X. Tuberculosis of the Testicle: Epididymectomy; Grafting of the Vas Deferens into the Globus Major. PMID- 17861641 TI - XI. Rupture of the Tendon of the Biceps Flexor Cubiti: A Case of Rupture of the Long Tendon in its Continuity, and one of Rupture of the Same Tendon at the Glenoid Attachment; Operation with Successful Result in Each Case. PMID- 17861642 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , January 11, 1905: Stated Meeting. PMID- 17861643 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , January 25, 1905: Stated Meeting. PMID- 17861644 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , February 6, 1905: Stated Meeting. PMID- 17861645 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , January 16, 1905: Stated Meeting. PMID- 17861647 TI - II. Subperitoneal Pelvic Fibromata: Its Surgical Treatment, with a Report of Two Cases. PMID- 17861646 TI - I. An Experimental and Histological Study of Cargile Membrane: With Reference to (1) Its Efficacy in Preventing Adhesion in the Abdominal and Cranial Cavities and Around Nerves and Tendons, and (2) Its Ultimate Fate in the Tissues. PMID- 17861648 TI - III. Gangrene of the Scrotum. PMID- 17861649 TI - IV. The Diagnosis and Treatment of Fracture of the Carpal Scaphoid and Dislocation of the Semilunar Bone: With a Report of Thirty Cases. PMID- 17861650 TI - V. The Relation of Gonorrhoeal Rheumatism to Seminal Vesiculitis, and its Cure by Seminal Vesiculotomy: A Report of Four Cases. PMID- 17861651 TI - VI. The Twine Triangular Stitch for Gastro- and Entero-enterostomy. PMID- 17861652 TI - VII. Suture of the Spleen for Traumatic Haemorrhage. PMID- 17861653 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , February 8, 1905: Stated Meeting. PMID- 17861654 TI - I. Of Ligature of the Innominate Artery: With Report of a Successful Case. PMID- 17861656 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , March 8, 1905: Stated Meeting. PMID- 17861655 TI - VIII. The Treatment of Congenital and Acquired Luxations at the Shoulder in Childhood. PMID- 17861658 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , February 6, 1905: Stated Meeting. PMID- 17861657 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , March 6, 1905: Stated Meeting. PMID- 17861659 TI - Cargile Membrane. PMID- 17861660 TI - II. Thyroidectomy for Exophthalmic Goitre. PMID- 17861661 TI - III. The Surgical Treatment of Tubercular Cervical Lymph-nodes: A Study of One Hundred Cases Submitted to Operation. PMID- 17861662 TI - IV. Drainage in Diffuse Septic Peritonitis. PMID- 17861664 TI - VI. Some Remarks on Cases involving Operative Loss of Continuity of the Common Bile Duct: With the Report of a Case of Anastomosis Between the Hepatic Duct and the Duodenum. PMID- 17861663 TI - V. Penetrating Bullet Wound of Abdomen passing through the Spleen, Stomach, Vertebra, and Spinal Cord: Laparotomy and Suture of Stomach Wounds; Recovery. Subsequent Laminectomy and Removal of Bullet from Spinal Cord; Recovery. PMID- 17861665 TI - VII. The Surgical Treatment of Chronic Mucomembranous and Ulcerative Colitis, with Special Reference to Technique. PMID- 17861667 TI - II. Scopolamine-Morphine as an Adjuvant in the Administration of General Anaesthesia. PMID- 17861666 TI - I. Final Results in the X-Ray Treatment of Cancer, Including Sarcoma. PMID- 17861668 TI - III. Scopolamine-Morphine Anaesthesia: Report on its Use in Seventy-Two Cases. PMID- 17861670 TI - V. Combined Volvulus and Hernia through a recent Mesenteric Slit: Resection of Five and One-Half Feet of Intestine; Death on Ninth Day. PMID- 17861669 TI - IV. Hypertrophic Pyloric Stenosis in the Infant. PMID- 17861671 TI - VI. The Cure of Femoral Hernia: Results of One Hundred and Ten Operations by a Single Method. PMID- 17861673 TI - VIII. Dislocation Forward of the Atlas, with Fracture of the Odontoid Process of the Axis. PMID- 17861672 TI - VII. Punctured Wounds of the Bladder: Report of a Case, with a Review of the Literature. PMID- 17861675 TI - X. The Treatment of Fractures of the Femur in Infancy and Childhood. PMID- 17861674 TI - IX. A New Interdental Splint for Fractures of the Lower Jaw. PMID- 17861676 TI - XI. Fracture of the Carpal Scaphoid. PMID- 17861678 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , March 22, 1905: Stated Meeting. PMID- 17861677 TI - XII. Transmesenteric Hernia of the Appendix Vermiformis. PMID- 17861680 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , March 6, 1905: Stated Meeting. PMID- 17861679 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , April 3, 1905: Stated Meeting. PMID- 17861681 TI - I. Dry Iodine Catgut. PMID- 17861682 TI - II. Dentigerous Cyst of the Lower Jaw: Situated at the Symphysis Menti. PMID- 17861683 TI - III. A Contribution to the Knowledge of Endothelioma and Perithelioma of Bone. PMID- 17861684 TI - IV. Malposition of the Appendix as a Cause of Functional Disturbances of the Intestine. PMID- 17861685 TI - V. The Radical Treatment of Cancer of the Rectum: With Particular Reference to the Value of Inguinal Colostomy. PMID- 17861686 TI - VI. Contusion and Laceration of the Mucous and Alar Ligaments and Synovial Fringes of the Knee-Joint. PMID- 17861687 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , April 12, 1905: Stated Meeting. PMID- 17861688 TI - I. Fracture of the Spine: A Summary of All the Cases (244) which were Treated at the Boston City Hospital from 1864 to 1905. PMID- 17861689 TI - II. A Case of Suture of the Spinal Cord following a Gunshot Injury involving Complete Severance of the Structure. PMID- 17861691 TI - IV. The Surgical Treatment of Intraspinal Tumors. PMID- 17861690 TI - III. Tubercular Conditions of the Spine requiring Surgical and Mechanical Relief. PMID- 17861692 TI - V. Studies in the Surgical Anatomy of the Small Intestine and Its Mesentery. PMID- 17861693 TI - VI. A Study of Infection of the Knee-Joint, based upon an Analysis of 310 Cases. PMID- 17861694 TI - VII. Fibrolipoma of Stomach: Removal by Resection of Stomach; Convalescence Complicated by Tetany. PMID- 17861695 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , April 26, 1905: Stated Meeting. PMID- 17861696 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , May 10, 1905: Stated Meeting. PMID- 17861697 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , May 1, 1905: Stated Meeting. PMID- 17861698 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , April 3, 1905: Stated Meeting. PMID- 17861699 TI - I. A Review of Five Hundred Cases of Gastro-Enterostomy, including Pyloroplasty, Gastroduodenostomy, and Gastrojejunostomy. PMID- 17861700 TI - II. Splenectomy for Myelogenous Leukaemia: Report of Later History of a Recovered Case, and Ultimate Death from Locomotor Ataxia. PMID- 17861701 TI - III. On Rupture of Intestine: With Report of a Case in which Rupture Occurred from Muscular Action, and Recovery Followed Operation. PMID- 17861702 TI - IV. The Management of Certain Critical Cases of Intestinal Obstruction, with Report of Cases: A. Resection for Cancerous Obstruction; B. Resection for Gangrenous Intussusception; C. Resection for Gangrene Due to Mesenteric Thrombosis. PMID- 17861703 TI - V. Angulation at the Sigmoid. PMID- 17861705 TI - VII. Lymphatic and Hepatic Infections Secondary to Appendicitis. PMID- 17861704 TI - VI. Mesocolic Hernia. PMID- 17861706 TI - VIII. Parotitis Following Appendectomy. PMID- 17861707 TI - IX. Acute Gangrenous Appendicitis in Typhoid Fever Simulating Perforation. PMID- 17861708 TI - X. Jaboulay's Anastomotic Button: An Experimental Study. PMID- 17861709 TI - XI. Tubercular Peritonitis in Woman. PMID- 17861710 TI - XII. Fracture of a Phalanx near the Epiphysis. PMID- 17861711 TI - XIII. As to the Necessity of Consent to Render Surgical Operations Lawful. PMID- 17861712 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , June 5, 1905: Stated Meeting. PMID- 17861713 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , May 1, 1905: Stated Meeting. PMID- 17861715 TI - VAN ARSDALE'S TRIANGULAR SPLINT IN THE TREATMENT OF FRACTURES OF THE FEMUR IN INFANCY AND CHILDHOOD. PMID- 17861714 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , June 7, 1905: Stated Meeting. PMID- 17861716 TI - LIGATURE OF THE INNOMINATE. PMID- 17861718 TI - II. Sarcoma of the Bladder: Report of a Case Occurring in a Child Four Years Old. PMID- 17861717 TI - I. Operative Treatment of Tumors of the Bladder: A Proposal to Substitute Bilateral Lumbar Nephrostomy and the Establishment of Renal Fistulae in Cases of Bladder Tumor, for Ureteral Implantation in Connection with Bladder Resection or Total Extirpation, and that the Bladder Operation be Done after an Interval and not Together with the Nephrostomies. PMID- 17861719 TI - III. Rupture of the Male Urinary Bladder: With an Account of Three Cases. PMID- 17861721 TI - V. The Rontgen Method in Lithiasis of the Urinary Tract. PMID- 17861720 TI - IV. Intraperitoneal Rupture of the Urinary Bladder: Recovery after Laparotomy and Bladder Suture. PMID- 17861723 TI - VII. Prostatic and Peri-prostatic Abscess: A Contribution to the Study of these Conditions and their Treatment by Operation. PMID- 17861722 TI - VI. Destroying the Urogential Diaphragm or Pelvic Floor as a means of Relieving Prostatic Ischuria. A new operation. PMID- 17861724 TI - CASE OF AN HERMAPHRODITE. PMID- 17861725 TI - VIII. The Law of Accelerating Risk in Cancer: A Mathematical Formula for Calculating the Expectancy and Post-Operative Prognosis of Malignant Growths. PMID- 17861726 TI - IX. The use of X-Rays in Carcinoma. PMID- 17861727 TI - X. Brown Atrophy of the Heart as a Result of Cholecystitis and as a Complication of Cholecystectomy. PMID- 17861728 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 11, 1905: Stated Meeting. PMID- 17861729 TI - SURGICAL PROGRESS. PMID- 17861730 TI - I. On Preservation of the Nerve Supply to the Brow, in the Operative Approach to the Gasserian Ganglion. PMID- 17861731 TI - XI. A Transverse Incision for the Removal of the Appendix. PMID- 17861732 TI - XII. The Radical Cure of Direct Inguinal Hernia. PMID- 17861733 TI - XIII. The Radical Cure of Severe Femoral and Inguinal Hernia. PMID- 17861734 TI - XIV. The Radical Operation for Inguinal Hernia: A Method for Closing all Layers with a Single Tier of Easily Removable Non-Buried Sutures. PMID- 17861735 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 25, 1905: Stated Meeting. PMID- 17861736 TI - III. Acute OEdema of the Lungs Secondary to Ether Narcosis. PMID- 17861737 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , October 2, 1905: Stated Meeting. PMID- 17861738 TI - Rupture of Intestine. PMID- 17861739 TI - Suture of Ruptured Biceps Tendon. PMID- 17861740 TI - IV. Excision of Portions of the Chest Wall for Malignant Tumors. PMID- 17861741 TI - V. Non-Parasitic Cysts of the Spleen. PMID- 17861742 TI - II. The Operative Treatment of Cleft Palate With a Report of Eight Cases. PMID- 17861743 TI - VI. Perforation of the Gall-Bladder. With a Report of Ten Cases. PMID- 17861744 TI - VII. The Value and Place of Duodenocholedochotomy in Gall-Stone Surgery. PMID- 17861745 TI - VIII. Construction of the Duodenum Below the Entrance of the Common Duct and Its Relation to Disease. PMID- 17861746 TI - IX. An Anomaly of the Duodenum Resulting in Death After Gastro-Enterostomy. PMID- 17861747 TI - X. Resection of Intestine, Followed by End-to-End Anastomosis Report of Cases. PMID- 17861748 TI - I. Surgical Intervention in Tuberculosis of the Meninges and of the Brain. PMID- 17861749 TI - II. The Elastic Ligature and the Ligature Method: Historical and Experimental Data from the Surgical Laboratory of the Medical Department of the University of California. PMID- 17861750 TI - III. The Reversal of the Circulation in a Limb. PMID- 17861751 TI - IV. Carcinomatous Metastases Developing over Three Years After Removal of the Breast without Local Recurrence. PMID- 17861753 TI - VI. The Treatment of Diffuse Septic Peritonitis. PMID- 17861752 TI - V. Cardio Spasm: With Report of an Operative Case. PMID- 17861755 TI - VIII. Two Cases of Rupture of the Bladder. PMID- 17861754 TI - VII. Extroversion of the Bladder: Relief by Transplantation of the Bladder into the Rectum. PMID- 17861756 TI - IX. Loose Bodies in the Knee Joint: With Report of Cases. PMID- 17861757 TI - X. An External Metal Support for Direct Application to the Shaft of a Fractured Long Bone. PMID- 17861758 TI - XI. The Use of Wolfe Grafts and Tendon-Lengthening in Treating Cicatricial Contractures. PMID- 17861759 TI - XII. Fractures of the Metacarpal Bones. PMID- 17861761 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , November 8, 1905: Stated Meeting. PMID- 17861760 TI - XIII. Fracture of the Astragalus with Subastragaloid Forward Dislocation of the Foot. Removal of the Entire Astragalus. PMID- 17861762 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , November 6, 1905: Stated Meeting. PMID- 17861763 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , January 2, 1906: Stated Meeting. PMID- 17861764 TI - I. Frontal and Ethmoid Sinus Empyema. Report of a Case Cured by Operation. PMID- 17861765 TI - II. Anatomy of a Case of Cystic Adenoma of the Thyroid Gland. PMID- 17861766 TI - III. The Results of the Surgical Treatment of Exopthalmic Goitre. PMID- 17861767 TI - IV. Impaction of a Toy Bicycle in the OEsophagus; Successful Removal by OEsophagotomy. PMID- 17861768 TI - V. Overlapping the Aponeuroses in the Closure of Wounds of the Abdominal Wall, Including Umbilical, Ventral and Inguinal Herniae. PMID- 17861769 TI - VI. Foreign-Body Pseudo Tuberculosis of the Peritoneum. PMID- 17861770 TI - VII. Solid Tumors of the Mesentery, with Report of a Case and a Review of the Literature. PMID- 17861771 TI - VIII. Chylous Cysts of the Mesentary. PMID- 17861772 TI - IX. Perforating Duodenal Ulcer. PMID- 17861773 TI - X. Practical Points in the Surgery of the Large Bowel, Exclusive of the Rectum with Illustrative Cases. PMID- 17861774 TI - XI. A Method of Permanent Drainage of Both Kidneys Through the Loin in Connection with Bilateral Nephrostomy. PMID- 17861775 TI - XII. Contribution to the Surgery of the Kidney Cases requiring Nephrectomy. PMID- 17861777 TI - XIV. The Effect Upon Glandular Tissue of Exposure to the X-Rays. PMID- 17861776 TI - XIII. A New Method of Excision of the Knee Without Opening the Joint. PMID- 17861779 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , December 4, 1905: Stated Meeting. PMID- 17861778 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , December 13, 1905: Stated Meeting. PMID- 17861780 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , November 3, 1905: Stated Meeting. PMID- 17861781 TI - I. The Value of the Differential Leucocyte Count in Acute Surgical Diseases. PMID- 17861782 TI - II. Fibrolipoma of Jaw and Neck. PMID- 17861783 TI - III. Discission of the Pleura in the Treatment of Chronic Empyema. PMID- 17861784 TI - IV. The Movements of the Stomach and Intestines in Some Surgical Conditions. PMID- 17861785 TI - V. The Technique of Gastrojejunostomy. PMID- 17861787 TI - VII. The Use of Silver Wire for the Cure of Large Herniae. PMID- 17861786 TI - VI. The Relative Value of Cecostomy and Appendostomy in the Treatment of Amebic Dysentery by Irrigation of the Colon. PMID- 17861788 TI - VIII. Primary Tumors of the Urinary Bladder: A Study of Forty-One Cases at the Massachusetts General Hospital. PMID- 17861790 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , January 10, 1906: Stated Meeting. PMID- 17861789 TI - IX. Ischemic Muscular Atrophy, Contractures and Paralysis. PMID- 17861791 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , January 24, 1906: Stated Meeting. PMID- 17861792 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , December 1, 1905: Stated Meeting. PMID- 17861793 TI - I. Resection of Portion of the Chest Wall and of the Diaphragm, for Primary Sarcoma of the Pleura. PMID- 17861794 TI - II. Observations on the Diagnosis and Treatment of Typhoid Perforation. PMID- 17861795 TI - III. Combined Operation for the Removal of the Appendix and the Cure of Right Inguinal Hernia. PMID- 17861796 TI - IV. Appendicular Femoral Hernia, with Notes of 100 Cases. PMID- 17861797 TI - V. Inguino-Properitoneal Hernia; Inguino-Interstitial Hernia: Report of Cases with Remarks. PMID- 17861798 TI - VI. The Etiology of Certain Congenital Tumors of the Groin: Their Relationship to Hernial Sacs. PMID- 17861799 TI - VII. The Determination of the Functional Capacity of the Kidneys. PMID- 17861800 TI - VIII. Ureteral Calculus. With a Report of Five Cases. PMID- 17861801 TI - IX. The Transperitoneal Examination of the Ureter in Cases of Suspected Ureteral Calculus, and the Combined Intra- and Extra-Peritoneal Uretero-Lithotomy. PMID- 17861802 TI - X. The X-Ray Findings in a Case of Gritti-Stokes Amputation. PMID- 17861803 TI - XI. Epiphyseal Separation of the Great Trochanter With Report of a Case. PMID- 17861804 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , February 14, 1906: Stated Meeting. PMID- 17861805 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , February 5, 1906: Stated Meeting. PMID- 17861806 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , January 5, 1906: Stated Meeting. PMID- 17861807 TI - CONNELL'S STITCH. PMID- 17861808 TI - BENNETT'S FRACTURE OF THE METACARPAL BONES. PMID- 17861810 TI - II. Branchial Fistula. PMID- 17861809 TI - I. Affections of the Thyroid Gland: A Clinical and Pathological Study. PMID- 17861811 TI - III. Diagnosis of Esophageal Lesions. PMID- 17861813 TI - V. Backward Dislocation of the Second Carpo-Metacarpal Articulation. PMID- 17861812 TI - IV. Postoperative Ileus. PMID- 17861814 TI - VI. Cornu Cutaneum of the Human Scalp. PMID- 17861816 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , November 22, 1905: Stated Meeting. PMID- 17861815 TI - VII. A Self-Retaining Trocar and Canula for the Aseptic Evacuation of Distended Viscera. PMID- 17861817 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , February 28, 1906: Stated Meeting. PMID- 17861818 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. , February 2, 1906: Stated Meeting. PMID- 17861819 TI - The Transverse Incision in Appendicitis. PMID- 17861820 TI - I. Hypertrophic Stenosis of the Pylorus in Infants. PMID- 17861821 TI - X. Wrist Resection by the Lateral Incision. PMID- 17861822 TI - XI. The Use of a Steel Comb for Dissection in the Axilla. PMID- 17861823 TI - XII. Postoperative Comfort. PMID- 17861824 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 14, 1906. PMID- 17861825 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 28, 1906. PMID- 17861826 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, March 5, 1906. PMID- 17861827 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. Stated Meeting, February 28, 1906. PMID- 17861828 TI - Overlapping Aponeurosis in Suture of Abdominal Wounds. PMID- 17861829 TI - II. Primary Sarcoma of the Omentum: Report of a Case and a Study of the Subject. PMID- 17861830 TI - III. The Surgical Aspects of Anuria. PMID- 17861831 TI - IV. Retroperitoneal Perirenal Lipomata: A Study of Large Retroperitoneal Lipomata of Perirenal Origin. The Technique of their Removal, Based on Anatomical Studies, with the Report of a Case. PMID- 17861833 TI - VI. Clinical Experiences with Meckel's Diverticulum and other Vestiges of the Omphalo-Mesenteric Duct. PMID- 17861832 TI - V. False Diverticula of the Vermiform Appendix. PMID- 17861834 TI - VII. A Method of Anastomosis of the Vasa Deferentia. PMID- 17861836 TI - IX. Wyeth's Method of Haemostasis in Amputation at the Hip and Shoulder: Report of Primary Amputations, one at the Hip Joint, the Other a Double Thigh and Shoulder Joint Amputation. PMID- 17861835 TI - VIII. Extraperitoneal Ligature of External Iliac Artery for Aneurism: Report of a Recent Case Followed by Recovery. PMID- 17861837 TI - I. On the use of the Masland Saw for Opening the Cranial Vault. PMID- 17861838 TI - II. On the use of the Temporal Fascia to Cover in Cranial Defects. PMID- 17861839 TI - III. Acute Septic Infection of the Throat and Neck; Ludwig's Angina. PMID- 17861840 TI - IV. Total Laryngectomy for Carcinoma: Report of a Recent Successful Case. PMID- 17861841 TI - V. The Treatment of Diffuse Suppurative Peritonitis, Following Appendicitis. PMID- 17861842 TI - VI. A Review of Fifteen Hundred Operations upon the Gall-Bladder and Bile Passages with Especial Reference to the Mortality. PMID- 17861843 TI - VII. Solitary Abscess of the Liver: A Contribution to the Pathology, Diagnosis. and Treatment of this Disease, Based on the Study of Eighteen Cases. PMID- 17861844 TI - VIII. The Treatment of Gastric and Duodenal Ulcers and Benign Obstructions of the Pylorus. PMID- 17861845 TI - IX. Volvulus of the Small Intestine in Typhoid Fever, Simulating Perforation. PMID- 17861846 TI - X. Myofibroma of the Large Intestine. PMID- 17861847 TI - XI. The Operative Treatment of Cancer of the Large Intestine, Causing Dangerous Intestinal Obstruction. PMID- 17861848 TI - XII. Individual Excision and Suture in Operating for the Removal of Hemorrhoids. PMID- 17861850 TI - XIV. Congenital Protrusion of Heart, Stomach, and Spleen: Case of Celosoma. PMID- 17861849 TI - XIII. The Treatment of Ectopia Vesicae. PMID- 17861852 TI - XVI. Dislocation of the Metatarsal Bones. PMID- 17861851 TI - XV. Chewing-Gum Nucleus of Vesical Calculus. PMID- 17861853 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 11, 1906. PMID- 17861854 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, April 2, 1906. PMID- 17861855 TI - I. The Serum Therapy of Tetanus. PMID- 17861856 TI - II. The Treatment of Tetanus by Magnesium Sulphate. PMID- 17861858 TI - IV. Report of a Case of Tumor of the Carotid Body. PMID- 17861857 TI - III. Early Operation in Traumatic Intracranial Hemorrhage. PMID- 17861859 TI - V. Shortening of the Round Ligaments by Subperitoneal Ventro-Aponeurotic Fixation. PMID- 17861860 TI - VI. An Experimental Study of Suture of Arteries, with a Description of a New Suture. PMID- 17861861 TI - VII. Combined Superior Tibiofibular and Astragalofibular Osteoplasty as a Means to Prevent Shortening of the Leg after Extensive Osteomyelitis of the Tibia Occurring during Adolescence. PMID- 17861862 TI - VIII. The Relation of the Technique of Nurses and of Hospital Apparatus to the Healing of Wounds. PMID- 17861863 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 25, 1906. PMID- 17861865 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. Stated Meeting, April 6, 1906. PMID- 17861864 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, May 7, 1906. PMID- 17861866 TI - Chewing-Gum and Ham-Rind as Nuclei of Vesical Calculi. PMID- 17861867 TI - Removal of Hemorrhoids by Excision and Suture. PMID- 17861868 TI - I. Filariasis. PMID- 17861870 TI - III. Cysts of the Urachus. PMID- 17861869 TI - II. The Radical Cure of Femoral Hernia. PMID- 17861871 TI - IV. On the Value of the Indigo-Carmin Test as an Aid in the Diagnosis of Partial and Total Ureteral Occlusions. PMID- 17861872 TI - V. Arteriovenous Anastomosis. PMID- 17861873 TI - VI. Prostatectomy in two Stages: A Conservative Operation with Minimum Hazard. PMID- 17861874 TI - VII. The Female Prostate: An Anatomico-Surgical Study. PMID- 17861876 TI - IX. A Method of Drainage of the Ankle Joint. PMID- 17861875 TI - VIII. Teratomata of the Inguinoscrotal Region Including a Review of Reported Cases. PMID- 17861878 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, May 9, 1906. PMID- 17861877 TI - X. Sarcoma and Myoma of the Stomach. PMID- 17861879 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. Stated Meeting, May 4, 1906. PMID- 17861880 TI - TRANSACTIONS OF THE CHICAGO SURGICAL SOCIETY. Stated Meeting, June 15, 1906. PMID- 17861881 TI - I. Dislocation of Vertebrae in Lower Cervical Region, Followed by Symptoms of Complete Severance of the Spinal Cord; Laminectomy; Later Partial Restoration of Function. PMID- 17861883 TI - III. A Further Report on a Case of Cirrhosis of the Stomach. PMID- 17861882 TI - II. The Omentum and its Functions. PMID- 17861884 TI - IV. Rupture of the Intestine: Report of Two Cases. PMID- 17861885 TI - V. Report of a Case of Intussusception Subjected to Operation: Colon Opened and Part of Intussusceptum Excised; Enterostomy for Fecal Drainage; Later Excision of Segment of Small Intestine and Enterorrhaphy for Suppression of Fecal Fistula; Ultimate Complete Recovery. PMID- 17861886 TI - VI. Angulation at the Sigmoid. PMID- 17861887 TI - VII. Hernia into the Ileocolic Fossa. PMID- 17861888 TI - VIII. Trans-Uretero-Ureteral Anastomosis. I. Intraperitoneal. II. Retroperitoneal: (a) Anterior to Aorta and Vena Cava; (b) Posterior to Aorta and Vena Cava. PMID- 17861890 TI - SURGICAL PROGRESS. PMID- 17861889 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, June 4, 1906. PMID- 17861891 TI - Remark upon "A New Method of Excision of the Knee without Opening the Joint.": In the Annals of Surgery, March, 1906. PMID- 17861892 TI - I. The Question of Early Operation in Cases of Intracranial Injury. PMID- 17861893 TI - II. Fracture of Base of Skull. Analysis of 530 Cases, with Particular Reference to Treatment and Prognosis. PMID- 17861895 TI - IV. The Bone Metastases of Hypernephroma. A Report from the Massachusetts General Hospital Clinic. PMID- 17861894 TI - III. On the Technique of Operations upon the Head and Neck. PMID- 17861896 TI - V. Cancer of the Gall-Bladder and Ducts. PMID- 17861898 TI - VII. Why Gastro-Enterostomy is Not a Harmless Operation. PMID- 17861897 TI - VI. Tumors of the Mesentery With Report of a Case of Fibroma. PMID- 17861899 TI - VIII. Surgical Treatment of Perforating Gastric Ulcer With Report of Three Cases, Two Acute and One Chronic. PMID- 17861901 TI - X. Aneurismal Varix. PMID- 17861900 TI - IX. Acute General Peritonitis Without Demonstrable Lesion. PMID- 17861903 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, October 1, 1906. PMID- 17861902 TI - XI. Coxa Vara. PMID- 17861904 TI - END-TO-END ARTERIOVENOUS ANGEIORRHAPHY. PMID- 17861905 TI - DRAINAGE OF THE PREVESICAL SPACE THROUGH THE PERINEUM IN SUPRAPUBIC CYSTOTOMY. PMID- 17861906 TI - DRAINAGE OF PROSTATIC ABSCESSES THROUGH THE ISCHIO-RECTAL FOSSA. PMID- 17861907 TI - SILVERIZED CATGUT: A STUDY OF THE METHOD OF CREDE FOR STERILIZING CATGUT WITHOUT HEAT. PMID- 17861908 TI - NOTE ON GONORRHOEAL OSTEOMYELITIS. PMID- 17861909 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 10, 1906. PMID- 17861910 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, October 24, 1906. PMID- 17861911 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 14, 1906. PMID- 17861912 TI - OCCLUSION OF THE PORTAL VEIN DUE TO SURROUNDING INFLAMMATORY ADHESIONS. PMID- 17861913 TI - OBLITERATION OF THE STOMACH AS A RESULT OF GASTRIC ULCER-DUODENOSTOMY. PMID- 17861914 TI - TYPHOID WITH DOUBLE PERFORATION OF ILEUM AND PERFORATION OF GALL-BLADDER: INTESTINAL SUTURE. CHOLECYSTECTOMY. PMID- 17861915 TI - INTESTINAL INTUSSUSCEPTION. PMID- 17861916 TI - RESECTION OF TEN FEET, TWO INCHES OF SMALL INTESTINE, WITH RECOVERY. PMID- 17861917 TI - FRACTURES OF THE OS CALCIS AND ASTRAGALUS. PMID- 17861918 TI - OLD FRACTURE OF THE TARSUS: WITH A REPORT OF SEVENTEEN CASES. PMID- 17861919 TI - ROTARY DISLOCATIONS OF THE ATLAS. PMID- 17861920 TI - COLOSSAL DERMOID CYST OF OVARY OF OVER FIFTY YEARS' GROWTH. PMID- 17861922 TI - INTRAPERITONEAL RUPTURE OF THE URINARY BLADDER: WITH REPORT OF A CASE OPERATED TWO HUNDRED AND FIFTY-FOUR HOURS AFTER ACCIDENT; WITH RECOVERY. PMID- 17861921 TI - EXTIRPATION OF A HYPERNEPHROMA, WEIGHING FOUR AND A QUARTER POUNDS, FROM AN INFANT TWENTY MONTHS OF AGE: RECOVERY. PMID- 17861923 TI - SEQUESTRATION ANAEMIA IN BRAIN AND SKULL SURGERY. PMID- 17861925 TI - PUERPERAL GENERAL PERITONITIS: REPORT OF ELEVEN CASES. PMID- 17861924 TI - PAPILLARY-CYSTADENOMATA OF THE BREAST: A REPORT ON TWENTY CASES OF THE PAPILLARY CYSTADENOMA TYPE OF FIBRO-EPITHELIAL TUMORS OF THE BREAST. PMID- 17861927 TI - REPORT OF A CASE IN WHICH A LARGE NUMBER OF FOREIGN BODIES WERE REMOVED FROM THE STOMACH. PMID- 17861926 TI - SUBACUTE PERFORATION OF THE STOMACH AND DUODENUM. PMID- 17861928 TI - SARCOMA OF THE SMALL INTESTINE AND MESENTERY: REPORT OF A CASE IN WHICH SIX FEET AND FIVE INCHES OF THE SMALL INTESTINE WERE REMOVED, WITH RECOVERY. PMID- 17861929 TI - CONGENITAL LUMBAR HERNIA, AT THE TRIANGLE OF PETIT. PMID- 17861930 TI - TUBERCULOSIS OF THE BLADDER. PMID- 17861931 TI - RECURRENT INTERMITTENT RETENTION OF URINE OCCURRING WITH THE REMISSIONS IN A CASE OF PERNICIOUS ANAEMIA-THE FINAL RESULT OF A BOTTINI OPERATION FOR ASSOCIATED PROSTATIC HYPERTROPHY. PMID- 17861933 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, November 28, 1906. PMID- 17861932 TI - ARTHROPLASTY UPON THE ELBOW JOINT. PMID- 17861935 TI - BONE METASTASES OF HYPERNEPHROMA. PMID- 17861934 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting held November 5, 1906. PMID- 17861936 TI - SARCOMA OF THE LONG BONES: THE DIAGNOSIS, TREATMENT AND PROGNOSIS, WITH A REPORT OF SIXTY-NINE CASES. PMID- 17861937 TI - SUCCESSFUL ANTERIOR THORACO-BRONCHOTOMY FOR A FOREIGN BODY IMPACTED IN THE BRONCHUS. PMID- 17861938 TI - THE SURGICAL TREATMENT OF EMPYEMA. PMID- 17861940 TI - TUBERCULOSIS OF THE BLADDER. PMID- 17861939 TI - CYSTS OF THE OMENTUM. PMID- 17861941 TI - DRAINAGE OF THE KNEE JOINT IN SEVERE INFECTIONS BY THE TRANSVERSE INCISION. PMID- 17861942 TI - DIFFUSE CAVERNOUS ANGEIOMA OF THE UPPER EXTREMITY. PMID- 17861943 TI - FRACTURE OF THE CORACOID PROCESS OF THE SCAPULA CAUSED BY MUSCULAR ACTION: WITH REPORT OF CASE. PMID- 17861944 TI - REPORT OF OPERATIONS: PERFORMED AT THE PUBLIC CLINICS FOR STUDENTS AT THE GERMAN HOSPITAL OF PHILADELPHIA, DURING THE SESSION OF 1905 TO 1906. PMID- 17861946 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, December 12, 1906. PMID- 17861945 TI - GLANDERS IN THE HUMAN SUBJECT: CLINICAL REPORT OF TWO CASES OBSERVED IN THE FOURTH MEDICAL DIVISION OF BELLEVUE HOSPITAL OF NEW YORK. PMID- 17861947 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting held December 3, 1906. PMID- 17861949 TI - POSSIBILITIES AND LIMITATIONS OF BRAIN SURGERY, WITH ESPECIAL VIEW TO TRAUMATISMS. PMID- 17861948 TI - EXPERIENCES IN CEREBRAL SURGERY. PMID- 17861950 TI - THE VALUE OF TREPHINING AS A PALLIATIVE MEASURE IN TUMORS OF THE BRAIN. PMID- 17861951 TI - THE OPERATIONS FOR NEOPLASMS OF THE TONGUE. PMID- 17861952 TI - A METHOD OF USING THE TONGUE IN SUPPLYING A DEFECT OF THE CHEEK. PMID- 17861953 TI - INJURIES AND DISEASES OF THE HYOID BONE. PMID- 17861954 TI - SYMPTOMS AND SIGNS IN URINARY LITHIASIS. PMID- 17861955 TI - TUBERCULOSIS OF THE BLADDER. PMID- 17861957 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 9, 1907. PMID- 17861956 TI - CIRCUMCISION.-A PLASTIC IN CONSTRICTED PREPUCES. PMID- 17861958 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting held January 7, 1907. PMID- 17861959 TI - SEVERE BURN OF TOP OF HEAD AT SEVEN MONTHS OF AGE, FOLLOWED BY NECROSIS OF ENTIRE OSSEOUS CAP OF CRANIUM: AT FOURTEEN YEARS OF AGE DETACHMENT OF THE ENTIRE CALVARIUM BY CIRCULAR CRANIOTOMY FOR EPILEPSY AND DEFECTIVE MENTAL DEVELOPMENT. PMID- 17861960 TI - THE SURGICAL TREATMENT OF TRIFACIAL NEURALGIA: WITH REPORT OF EIGHT CASES OF RESECTION OF THE GASSERIAN GANGLION. PMID- 17861961 TI - REPORT OF A CASE OF HAEMOPHILIC KNEE JOINT. OPERATION; RECOVERY UNDER THE USE OF THYROID EXTRACT. PMID- 17861962 TI - STAB WOUNDS OF THE HEART: WITH REPORT OF A CASE. PMID- 17861963 TI - HERNIA OF STOMACH THROUGH THE DIAPHRAGM INTO THE THORAX. PMID- 17861964 TI - NOTE ON CARCINOMA OF THE CARDIAC END OF THE STOMACH. PMID- 17861965 TI - A CRITICAL REVIEW OF A RECENT SERIES OF OPERATIONS UPON THE STOMACH. PMID- 17861966 TI - THE LESIONS ASSOCIATED WITH GUNSHOT WOUNDS OF THE STOMACH. PMID- 17861967 TI - DUODENAL FISTULA: ITS TREATMENT BY GASTROJEJUNOSTOMY AND PYLORIC OCCLUSION. PMID- 17861968 TI - ILEOCAECAL INTUSSUSCEPTION DUE TO MYOADENOMA OF THE ILEUM. PMID- 17861970 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, January 23, 1907. PMID- 17861969 TI - THE SURGICAL TREATMENT OF SPLANCHNOPTOSIS. PMID- 17861971 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, February 13, 1907. PMID- 17861972 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, February 4, 1907. PMID- 17861973 TI - PLASTIC RESECTION OF THE MAMMARY GLAND. PMID- 17861974 TI - THE CONTRIBUTIONS OF SURGERY TO A BETTER UNDERSTANDING OF GASTRIC AND DUODENAL ULCER. PMID- 17861975 TI - END RESULTS IN BENIGN LESIONS OF THE STOMACH SURGICALLY TREATED. PMID- 17861976 TI - REMOTE OR INDIRECT SUBPERITONEAL DRAINAGE IN THE EXTRAPERITONEAL CLOSURE OF PERSISTENT FAECAL FISTULAE. PMID- 17861977 TI - LIPOMA OF THE INTESTINE OCCURRING IN A CHILD THIRTEEN MONTHS OLD AND CAUSING SYMPTOMS OF INTESTINAL OBSTRUCTION. PMID- 17861978 TI - A MALIGNANT TYPE OF PSEUDOMYXOMA PERITONEI PENETRATING THE SPLEEN AND COLON. PMID- 17861980 TI - THE ADEQUACY OF LOCAL ANAESTHESIA IN INGUINAL HERNIA OPERATIONS. PMID- 17861979 TI - PRIMARY TYPHLITIS WITHOUT APPENDICITIS. PMID- 17861981 TI - CYSTS OF THE SUPRARENAL GLAND. PMID- 17861982 TI - TOXIC NEPHRITIS DEPENDENT UPON SURGICAL CONDITIONS. PMID- 17861983 TI - THE DIAGNOSIS OF OBSCURE CASES OF RENAL AND URETERAL CALCULUS. PMID- 17861984 TI - TUBERCULOSIS OF THE TESTICLE: OBSERVATIONS UPON 100 PATIENTS. PMID- 17861985 TI - I. FRACTURE OF THE GREATER TUBEROSITY OF THE HUMERUS, WITH DISLOCATION OF THE HUMERUS INTO THE AXILLA. IMMEDIATE REDUCTION OF DISLOCATION. ON SEVENTH DAY NAILING OF FRAGMENT OF TUBEROSITY IN PLACE. PMID- 17861986 TI - II. FRACTURE AT THE ANATOMICAL NECK OF THE HUMERUS AND DISLOCATION OF THE HEAD INTO THE AXILLA, WITH FRACTURE OF THE SHAFT. DIFFICULT REMOVAL OF HEAD OF HUMERUS. PMID- 17861987 TI - PARTIAL GASTRECTOMY: WITH REPORT OF TWO CASES. PMID- 17861989 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, held March 4, 1907. PMID- 17861988 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, February 27, 1907. PMID- 17861990 TI - I. The Results of Radical Operations for the Cure of Carcinoma of the Breast. PMID- 17861991 TI - XII. Acute Diffuse Gonorrhoeal Peritonitis. PMID- 17861992 TI - XIII. Some Practical Deductions from Personal Experience in the Treatment of Appendicitis. PMID- 17861994 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 13, 1907. PMID- 17861993 TI - XIV. Motor-Boat Fractures. PMID- 17861997 TI - III. Final Results in 164 Cases of Carcinoma of the Breast Operated upon during the Past Fourteen Years at the Augustana Hospital. PMID- 17861996 TI - II. End Results of 376 Primary Operations for Carcinoma of the Breast at the Massachusetts General Hospital, between January 1, 1894, and January 1, 1904. PMID- 17861995 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, March 27, 1907. PMID- 17861998 TI - IV. End Results following Operations for Carcinoma of the Breast. PMID- 17861999 TI - V. The End Results following Operations for Carcinoma of the Breast. PMID- 17862000 TI - VI. Carcinoma of the Breast A Study of the Pathological Conditions and Their Relation to the Question of Recurrence. PMID- 17862001 TI - VII. End Results following Operations for Carcinoma of the Breast. PMID- 17862002 TI - VIII. Very Late Recurrences after Operation for Carcinoma of the Breast. PMID- 17862003 TI - IX. Carcinoma of the Bones following Carcinoma of the Breast. PMID- 17862004 TI - X. Thymus Gland Treatment of Cancer: A Preliminary Report with a Presentation of a Case of Inoperable Cancer with Great Relief of Symptoms. PMID- 17862005 TI - XI. Peritoneal Tuberculosis. PMID- 17862006 TI - I. Avulsion of the Spine of the Tibia. PMID- 17862007 TI - II. Osteogenesis Imperfecta and Idiopathic Fragilitas Ossium. PMID- 17862008 TI - III. Traumatic Epithelial Cysts. PMID- 17862009 TI - IV. Syphilis of the Bones and Some Radiographic Findings. PMID- 17862010 TI - V. The Correction of Certain Forms of "Saddle-Nose.". PMID- 17862011 TI - VI. Intussusception. PMID- 17862012 TI - VII. Operation in Two Stages for Relief of Ileus of Jejunum. PMID- 17862013 TI - VIII. An Enormous Cyst of the Urachus: Extirpation and Recovery. PMID- 17862014 TI - IX. Ureteritis Cystica Chronica: Report of a Case with Bilateral Double Ureters. PMID- 17862015 TI - X. Operation for Hypospadias. PMID- 17862016 TI - XI. A Male Pseudo-Hermaphrodite. PMID- 17862017 TI - XII. A New Retractor to be Used in Suprapubic Cystotomy. PMID- 17862018 TI - XIII. Multiple Fractures, with an Analysis of 240 Cases, etc. PMID- 17862019 TI - XIV. Fractures of the Head and Neck of the Radius. PMID- 17862020 TI - XV. Isolated Fracture of the Great Trochanter. PMID- 17862021 TI - XVI. Post-Operative Treatment. PMID- 17862022 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 10, 1907. PMID- 17862023 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, April 1, 1907. PMID- 17862025 TI - II. Arteriovenous Anastomosis. PMID- 17862024 TI - I. The Technique of Direct Transfusion of Blood. PMID- 17862026 TI - III. Ligation of the Ductus Arteriosus. PMID- 17862027 TI - IV. Arteriotomy for Thrombosis and Embolism. PMID- 17862028 TI - V. Technique of Blood Vessel Suture. PMID- 17862029 TI - VI. Endo-Aneurysmorrhaphy (Matas). PMID- 17862030 TI - VII. Endo-Aneurysmorrhaphy (Matas). PMID- 17862031 TI - VIII. The Suture of Blood Vessels. Implantation and Transplantation of Vessels and Organs. An Historical and Experimental Study. PMID- 17862032 TI - IX. The Operative Treatment of Acute Abscess of the Lung. PMID- 17862033 TI - X. Concerning a Distinct Type of Hypernephroma of the Kidney, which Simulates Various Cystic Conditions of that Organ. PMID- 17862034 TI - XI. The Extension of the Field of Treatment of Certain Renal and Vesical Conditions that is made Available by a New Contrivance for Long Continued or Permanent Drainage of the Kidneys through Renal Fistula in the Loin. PMID- 17862035 TI - XII. Upon Certain Aspects of Calculous Anuria with Especial Reference to the Performance of Bilateral Nephrolithotomy Simultaneously in Some Cases of this Condition. PMID- 17862036 TI - XIII. A New Combined Lithotrite with Cystoscope. PMID- 17862037 TI - XIV. A Telephonic Searcher for Use in the Bladder. PMID- 17862039 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, April 24, 1907. PMID- 17862038 TI - XV. "Gauze-Ether," or a Modified Drop Method, with its Effect on Acetonuria. PMID- 17862040 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, May 6, 1907. PMID- 17862041 TI - Influence of Pregnancy on Cancer of the Breast. PMID- 17862042 TI - I. The Parathyroid Glandules. Their Blood Supply and their Preservation in Operation upon the Thyroid Gland. PMID- 17862043 TI - II. Tetany Parathyreopriva: A Case Report, with a Brief Discussion of the Disease and of the Parathyroid Glands. PMID- 17862044 TI - III. Observations upon a Form of Exophthalmic Goitre Occurring in a Dog. PMID- 17862045 TI - IV. Experimental Studies upon the Thoracic OEsophagus-a Preliminary Report. PMID- 17862046 TI - V. Studies Upon the Function of the Pylorus and Stoma after Gastroenterostomy has been Performed. PMID- 17862047 TI - VI. Is Death in High Intestinal Obstruction Due to the Absorption of Bile? PMID- 17862048 TI - VII. Studies in Intestinal Exclusion. PMID- 17862049 TI - VIII. Are the Intestines Able to Propel their Contents in an Anti-Peristaltic Direction? PMID- 17862050 TI - IX. Rectal Anaesthesia: Experimental Studies together with a Report of its Practical Employment at Roosevelt Hospital. PMID- 17862051 TI - X. Tuberculins and the Tuberculo-Opsonic Index. PMID- 17862052 TI - XI. Tumor of the Cauda Equina Removed by Operation: Recovery. PMID- 17862054 TI - XIII. Tuberculosis of the Elbow, Arthroplasty. PMID- 17862053 TI - XII. Multiple Exostoses, Including an Exostosis within the Spinal Canal with Surgical and Neurological Observations. PMID- 17862056 TI - XV. Partial Loss of the Tibia Replaced by Transfer of the Fibula, with Maintenance of both Malleoli of the Ankle. PMID- 17862055 TI - XIV. Old Unreduced Posterior Dislocations of the Shoulder. PMID- 17862057 TI - XVI. Fracture of the Tarsal Scaphoid Bone: With Report of Three Cases. PMID- 17862058 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, May 8, 1907. PMID- 17862059 TI - Fracture-Dislocation Head of Humerus. PMID- 17862060 TI - I. Multiple Carcinomata following Chronic X-ray Dermatitis. PMID- 17862061 TI - II. Phagedenic Ulceration of both Breasts during the Puerperium. PMID- 17862062 TI - III. Cutaneous Horns: A Report of Three Cases. PMID- 17862063 TI - IV. Traumatic Hematomyelia: With a Report of a Case. PMID- 17862064 TI - V. Nerve Disassociation; A New Method for the Surgical Relief of Certain Painful or Paralytic Affections of Nerve Trunks. PMID- 17862065 TI - VI. Operations on the Spinal Column. PMID- 17862066 TI - VII. The Surgery of the Thoracic Duct. PMID- 17862067 TI - VIII. Dermoid Cyst of the Head: Excision, Using Crile's Temporary Clamp on the Common Carotid. PMID- 17862068 TI - IX. Stylo-hyoid Ossification. PMID- 17862070 TI - XI. Tuberculosis of the Caecum: With a Report of Two Cases. PMID- 17862069 TI - X. Acute Dilatation of the Stomach-Gastro-mesenteric Ileus. PMID- 17862071 TI - XII. Strangulation Resulting from Distention of Hollow Viscera: Its Bearing Upon Appendicitis, Strangulated Hernia and Gall-Bladder Disease. PMID- 17862072 TI - XIII. Abnormal Ileo-appendicular Fold as a Cause of Partial Occlusion of the Bowel. PMID- 17862073 TI - XIV. A New Liver Suture. PMID- 17862075 TI - I. Carcinoma of the OEsophagus: A Clinical and Pathological Study from the Pathological Department of the St. Louis University Medical School. PMID- 17862074 TI - XV. The Operative Treatment of Calculi Impacted in the Pelvic Portion of the Ureter. PMID- 17862076 TI - II. Tonsillar Hemorrhage and its Surgical Treatment. PMID- 17862078 TI - IV. Report of a Case of Sarcoma of the Thyroid. PMID- 17862077 TI - III. Lingual Goitre. PMID- 17862079 TI - V. Narath's Modification of Talma's Operation for Hepatic Cirrhosis. PMID- 17862081 TI - VII. Primary Fibromyomata of the Broad Ligaments. PMID- 17862080 TI - VI. Acute Pancreatitis: With Report of Two Cases. PMID- 17862083 TI - IX. The Conservative Surgical Treatment of the Hypertrophy of the Prostate Gland in the Very Feeble and Aged. PMID- 17862082 TI - VIII. The Renal Catheter as an Aid in the Diagnosis of Valve-like Obstruction of the Ureter. PMID- 17862084 TI - X. Epithelioma of the Penis. An Analysis of One Hundred Cases. PMID- 17862085 TI - XI. The "Bottle Operation" Method for the Radical Cure of Hydrocele. PMID- 17862086 TI - XII. Bilateral Tuberculous Bursitis of the Hips. PMID- 17862087 TI - XIII. The "Suspender" Abdominal Bandage. The Four-Tailed Genital Bandage. PMID- 17862088 TI - XIV. Surgical Progress. PMID- 17862089 TI - Subsequent Report on a Case of Severe Spinal Cord Injury: Symptoms of Complete Severance of the Cord. PMID- 17862090 TI - I. The Relation of the Mesocolic Band to Gastroenterostomy. PMID- 17862091 TI - III. Isolated Fracture of the Greater Tuberosity of the Humerus. PMID- 17862092 TI - XVI. Punctured Fracture of the Skull. PMID- 17862093 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, October 9, 1907. PMID- 17862094 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, October 23, 1907. PMID- 17862096 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, October 1, 1907. PMID- 17862095 TI - IV. A Contribution to the Diagnosis of Renal Tuberculosis. PMID- 17862097 TI - V. Excision of the Whole Left Lobe of the Liver for Sarcoma. PMID- 17862099 TI - VII. Splenectomy for Gunshot Wound of the Spleen. PMID- 17862098 TI - VI. Splenectomy for Lacerated Spleen, after Blood Transfusion. PMID- 17862100 TI - II. Intracranial Abscess Due to the Typhoid Bacillus. PMID- 17862101 TI - VIII. Splenectomy in Banti's Disease, with Report of a Case. PMID- 17862102 TI - IX. Splenectomy for Carcinoma. PMID- 17862103 TI - X. Gangrene of Appendix in a Three Weeks' Old Infant. PMID- 17862104 TI - XI. Primary Sarcoma of the Prostate. PMID- 17862105 TI - XII. A Systematic Operation for Penile Hypospadias and Other Defects of the Urethral Floor. PMID- 17862106 TI - XIII. Simple Fracture of the Carpal Scaphoid: With a Report of Seven Cases. PMID- 17862107 TI - XIV. Observations on the Treatment of Fracture of the Neck of the Femur in 112 Cases. PMID- 17862108 TI - XV. The Open Method in the Treatment of Pott's Fracture of the Leg. PMID- 17862109 TI - I. Ludwig's Augina. An Anatomical, Clinical, and Statistical Study. PMID- 17862110 TI - II. Experimental Surgery of the Lungs: I. Thirty Animal Operations Under Positive Pressure. (A Preliminary Report.). PMID- 17862111 TI - III. Should Cholecystitis and Cholelithiasis be Any Longer Considered Medical Affections, and What are the Usual Consequences of So Treating Them? PMID- 17862112 TI - IV. The Value of the Differential Leucocyte Count in Acute Appendicitis. PMID- 17862113 TI - V. A new Technique for Dealing with the Appendix Stump. PMID- 17862114 TI - VI. Obstruction of the Internal Urinary Meatus by Folds of Mucosa. PMID- 17862115 TI - VII. Postoperative X-ray Treatment of Malignant Disease. PMID- 17862116 TI - VIII. Endo-aneurysmorrhaphy (Matas) in the Treatment of Traumatic Aneurysm of the Femoral Artery. PMID- 17862118 TI - X. The Trough-suspender Forearm Sling. PMID- 17862117 TI - IX. Further Observations on the Treatment of Paralytic Talipes Calcaneus by Astragalectomy and Backward Displacement of the Foot. PMID- 17862119 TI - XI. Partial Resection of the Upper and Lower Maxillae for Congenital Deformity of the Face. PMID- 17862120 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, November 13, 1907. PMID- 17862121 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, November 4, 1907. PMID- 17862122 TI - I. Tracheo-Bronchoscopy: With Report of Cases. PMID- 17862124 TI - III. Ludwig's Angina (Part II): An Anatomical, Clinical and Statistical Study. PMID- 17862123 TI - II. Trichinous Infection of a Carcinoma of the Lip. PMID- 17862126 TI - V. Rupture of the Lung Without Costal Injury: With the Report of a Case. PMID- 17862125 TI - IV. Studies in Technique of Cancer of the Breast Operation. PMID- 17862127 TI - VI. Acute Dilatation of the Stomach and Arterio-Mesenteric Ileus. PMID- 17862128 TI - VII. Unilateral Renal Hematuria Due to Pyelitis Cystica. PMID- 17862129 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, November 27, 1907. PMID- 17862130 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, December 11, 1907. PMID- 17862131 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, December 2, 1907. PMID- 17862132 TI - The Bottle Operation for Hydrocele. PMID- 17862133 TI - CORRESPONDENCE. PMID- 17862134 TI - I. The Direction of the Jejunum in the Operation of Gastro-enterostomy. PMID- 17862135 TI - II. Transfusion and Arterial Anastomosis: Some Experiments in Arterial Anastomosis and a Study of Transfusion with Presentation of Two Clinical Cases. PMID- 17862136 TI - III. On the Thymus Gland Treatment of Cancer: Second Paper. PMID- 17862137 TI - IV. The Parathyroid Glands. PMID- 17862138 TI - V. Acute Dilatation of the Stomach and Arterio-Mesenteric Ileus. PMID- 17862139 TI - VI. The Removal of Gall Stones from the Second and Third Portions of the Common Bile Duct. PMID- 17862141 TI - VIII. Diagnosis of Renal Disease and Sufficiency. PMID- 17862140 TI - VII. The Reduction En Masse of Strangulated and Non-Strangulated Herniae. PMID- 17862142 TI - IX. Multiple and Consecutive Operations on the Kidneys for Calculi. PMID- 17862143 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, January 8, 1908. PMID- 17862144 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, January 6, 1908. PMID- 17862145 TI - I. Subtemporal Decompressive Operations for the Intracranial Complications Associated with Bursting Fractures of the Skull. PMID- 17862146 TI - II. Osteoplastic Resection of the Skull, with Description of a Modification of Stellwagen's Instrument for Performing this Operation. PMID- 17862147 TI - III. Atlo-Occipital Dislocation: A Case of Fracture of the Atlas and Axis, and Forward Dislocation of the Occiput on the Spinal Column, Life being Maintained for Thirty-four Hours and Forty Minutes by Artificial Respiration, during which a Laminectomy was Performed upon the Third Cervical Vertebra. PMID- 17862148 TI - IV. Fracture through the Anatomical Neck of the Humerus with Dislocation of the Head. PMID- 17862149 TI - V. The Treatment of Dislocation of the Shoulder-Joint Complicated by Fracture of the Upper Extremity of the Humerus, with an Analysis of Sixty-three Cases with Fracture at the Neck of the Humerus and Twenty-one Cases with Fracture of the Greater Tuberosity reported since 1894. PMID- 17862150 TI - VI. A Treatment of Epiphyseal Displacements and Fractures of the Upper Extremity of the Humerus Designed to Assure Definite Adjustment and Fixation of the Fragments. PMID- 17862151 TI - VII. Traumatic Subluxation of the Humerus. PMID- 17862152 TI - VIII. Occluding Pulmonary Embolism. PMID- 17862153 TI - IX. Primary Carcinoma of the Hepatic Ducts: the Report of a Case with the Autopsy. PMID- 17862154 TI - X. The Operative Treatment of Intractable Vomiting, Not Due to Pyloric Obstruction-Neurosis of the Stomach. PMID- 17862155 TI - XI. The Value of Enterostomy and Conservative Operative Methods in the Surgical Treatment of Acute Intestinal Obstruction, with Remarks on the Importance of Operations in Two Stages. PMID- 17862156 TI - XII. The Non-Absorbable Suture and Ligature. PMID- 17862157 TI - XIII. Report of Saturday Surgical Clinics for Students, held at the German Hospital of Philadelphia. 1906 and 1907. PMID- 17862158 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, January 22, 1908. PMID- 17862159 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, February 12, 1908. PMID- 17862160 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, February 3, 1908. PMID- 17862161 TI - XIV. Carcinoma of the Appendix with Metastasis to the Ileocolic Glands. PMID- 17862162 TI - XV. Splenectomy in Banti's Disease: Followed by OEdema of the Large Intestine with Localized Necrosis of its Wall. PMID- 17862163 TI - XVI Stone in the Bladder, Associated with Intermittent Pneumaturia. PMID- 17862164 TI - XVII. Results of Operation on the Kidney for Calculus and Tuberculosis. PMID- 17862165 TI - XVIII. Stone, Tuberculosis of the Kidney, and Perinephric Abscess. PMID- 17862166 TI - XIX. Report of a Case of Large Renal Calculus. PMID- 17862167 TI - XX. Primary Carcinoma of the Female Urethra. PMID- 17862168 TI - XXI. Pelvic Abscess, with Special Reference to Rectal Drainage. PMID- 17862169 TI - XXII. Treatment of Fractures of the Femur: Extension Made from Traction Below the Knee of the Injured, and Counter-Extension Through a Similar Position from the Immobilized Uninjured Limb. PMID- 17862170 TI - XXIII. Modern Medicine and Surgery in the Orient. PMID- 17862171 TI - TRANSACTIONS OF THE AMERICAN SURGICAL ASSOCIATION Annual Meeting, May 4, 5, and 6, 1908. PMID- 17862172 TI - I. Reminiscences of the Early Days of the American Surgical Association. PMID- 17862174 TI - III. Psychical Aspects of Graves' Disease. PMID- 17862173 TI - II. Psychical End-Results following Major Surgical Operations. PMID- 17862175 TI - IV. Treatment of Perforative Peritonitis: General Free Suppurative. PMID- 17862176 TI - V. Late Results after Operations for Benign Diseases of Stomach and Duodenum. PMID- 17862177 TI - VI. A Study of Gastric and Duodenal Ulcers: With Especial Reference to their Surgical Cure. PMID- 17862178 TI - VII. End-Results following Operation for Benign Diseases of the Stomach and Duodenum. PMID- 17862180 TI - IX. Gastric and Duodenal Ulcers Secondary to Wounds of the Urinary Bladder. PMID- 17862179 TI - VIII. How Frequently do Gastric Ulcers become Carcinomata? PMID- 17862182 TI - XI. Melanotic Sarcoma of the Common Bile Duct, etc. PMID- 17862181 TI - X. Infantile Hypertrophic Stenosis of Pylorus. PMID- 17862183 TI - XII. Experiments in Flushing the Intestinal Canal, etc: A Series of Studies on Animals and on Human Cadavers for the Purpose of Determining Whether it is Practicable to Attempt to Remove a Part, or the Whole, of the Intestinal Contents by Washing out the Canal of the Small Intestine Through Enterotomy Openings, Systematically from Above Downwards; and, Finally, by Washing out the Colon from the Lowest Enterotomy Opening, the Contents of the Colon and Wash Water Escaping from the Anus. PMID- 17862184 TI - XIII. Primary Carcinoma and Sarcoma of the Appendix. PMID- 17862185 TI - I. Aneurysmorrhaphy. Treatment of Popliteal Aneurysm by the Reconstructive Method. PMID- 17862186 TI - II. Aneurysmorrhaphy. Personal Experience with the Modern Method of Treating Aneurysm. PMID- 17862187 TI - XIII. Transperitoneal Removal of Tumors of the Bladder. PMID- 17862188 TI - XIV. Ainhum: With Report of a Case. PMID- 17862189 TI - XV. Arrest of Growth at the Lower End of the Radius after Separation of its Epiphysis. PMID- 17862190 TI - XVI. Strain-fractures of the Knee. PMID- 17862191 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , February 26, 1908: Stated Meeting. PMID- 17862192 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , March 11, 1908: Stated Meeting. PMID- 17862194 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , March 2, 1908: Stated Meeting. PMID- 17862193 TI - III. Aneurysmorrhaphy. A Case of Popliteal Aneurysm Presenting Unusual Difficulties in the Application of the Matas Operation. PMID- 17862196 TI - V. Ligation of the Left Common Iliac Artery, with Report of a Recent Case. PMID- 17862195 TI - IV. The Serous Coat of Blood Vessels Compared with the Peritoneum. PMID- 17862197 TI - VI. The Question of Operation for Non-penetrating Intracranial Trauma. PMID- 17862198 TI - VII. Splenectomy. Report of Six Cases, together with a Statistical Summary of all the Reported Operations up to the Year 1908. PMID- 17862199 TI - VIII. Subcutaneous Rupture of the Spleen Report of Cases with Remarks. PMID- 17862200 TI - IX. Gangrene of the Gall Bladder. PMID- 17862201 TI - X. The Treatment of the Appendix Stump after Appendectomy. PMID- 17862202 TI - XI. Excision of Carcinoma of the Rectum by the Combined Method: With Report of Three Cases. PMID- 17862204 TI - I. Tetany following Thyroidectomy Cured by the Subcutaneous Injection of Parathyroid Emulsion. PMID- 17862203 TI - XII. The Diagnosis and Prognosis of Tuberculous and Septic Conditions of the Kidney. PMID- 17862205 TI - II. Sinus of First Branchial Cleft. PMID- 17862207 TI - IV. Desmoid Tumors of the Abdominal Wall. PMID- 17862206 TI - III. Technique of Early Operation for the Removal of Tubercular Cervical Lymph Nodes. PMID- 17862208 TI - V. Note on Syphilis of the Liver: With a Report of Three Cases in which Operation was Resorted to. PMID- 17862209 TI - VI. Primary Carcinoma of the Vermiform Appendix. PMID- 17862210 TI - VII. Hernia of the Appendix, Complicated with Appendicitis. PMID- 17862211 TI - VIII. Enormous Endotheliomatous Cyst of the Great Omentum. PMID- 17862212 TI - IX. The Inconsistencies of the Gauze Pack. PMID- 17862213 TI - X. Prevesical Abscess. PMID- 17862214 TI - XI. Symptomless Hematuria: Report of Three Cases in which Hemorrhage Ceased after Catheterization of the Ureters. PMID- 17862215 TI - XII. Cystic Degeneration of the Kidney. PMID- 17862216 TI - XIII. Venous Thrombosis and Hydrocele of the Inguinal Canal. PMID- 17862218 TI - XV. Contribution to the Surgery of the Prostate: A. The Restoration of Voluntary Control of the Uro-Genital Sphincter in Cases of Incontinence of Urine Following Operations Upon the Prostate. B. An Operative Device in the Treatment of Urethro Rectal Fistulae. PMID- 17862217 TI - XIV. Comparative Value of Various Measures for Relief of Prostatic Enlargement. PMID- 17862219 TI - XVI. Musculo-spiral (Radial) Paralysis due to Dislocations of the Head of the Radius: With Especial Reference to those Cases Complicating Fracture of New York. PMID- 17862221 TI - XVIII. The Surgical Treatment of Bunion. PMID- 17862220 TI - XVII. Congenital Defect in the Ulna. PMID- 17862223 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , March 25, 1908: Stated Meeting. PMID- 17862222 TI - XIX. A New Motor for Bone Surgery. PMID- 17862224 TI - I. The Treatment of the Undescended or Maldescended Testis associated with Inguinal Hernia. PMID- 17862225 TI - II. Operation for Undescended Testicle. PMID- 17862226 TI - III. The Radical Treatment of Carcinoma of the Bladder. PMID- 17862227 TI - IV. Disturbances due to Disease of the Verumontanum and its Treatment with the Posterior Urethroscope. PMID- 17862229 TI - VI. Haematuria as a Complicating Factor in Appendicitis. PMID- 17862228 TI - V. Fibrinous Calculi in the Kidney. PMID- 17862230 TI - VII. Volkmann's Ischemic Paralysis. PMID- 17862231 TI - VIII. Recurrent Dislocation of the Ulnar Nerve. Report of a Second Case Cured by Operation. PMID- 17862232 TI - IX. The Operative Treatment of Recent Fractures of the Femoral Shaft. PMID- 17862233 TI - X. Reduction of Supracondyloid Fracture of Humerus: (Extension Type) by Preliminary Hyperextension of the Forearm, and Maintenance of the Reduction by Extreme Flexion. PMID- 17862235 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , April 8, 1908: Stated Meeting. PMID- 17862234 TI - XI. Twenty-five Hundred Cases of Gas-ether Anaesthesia without Complication. PMID- 17862236 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, April 22, 1908. PMID- 17862237 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , April 6, 1908: Stated Meeting. PMID- 17862238 TI - I. Cancer of the Mouth and Tongue. PMID- 17862239 TI - II. A Method of Operation in Extensive Cancerous Growths of the Cheek Involving the Jaw. PMID- 17862240 TI - III. Recurrence at a Late Period After Operation for Cancer of the Breast. PMID- 17862242 TI - V. Notes on the Arrest of Hepatic Hemorrhage Due to Trauma. PMID- 17862241 TI - IV. Osteoplastic Resection of the Costal Arch, followed by Resection of Lesser Curvature of Stomach and Oesophagus, and Oesophagostomy. PMID- 17862243 TI - VI. Cause of Sudden Fall in Blood-Pressure while Exploring the Common Bile-Duct. PMID- 17862245 TI - VIII. Primary Carcinoma of the Appendix: Report of Two Cases. PMID- 17862244 TI - VII. A Method to Facilitate the Avoidance of Infection During Intestinal Anastomosis-Preliminary Report. PMID- 17862246 TI - IX. Carcinoma of the Appendix Vermiformis. PMID- 17862247 TI - X. Chyle Cysts of the Mesentery. PMID- 17862248 TI - XI. The Etiology of Hydronephrosis. PMID- 17862250 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , May 4, 1908: Stated Meeting. PMID- 17862249 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , May 13, 1908: Stated Meeting. PMID- 17862251 TI - I. The use of Ethyl Chloride as a General Anaesthetic in the Pennsylvania Hospital. PMID- 17862252 TI - II. Ludwig's Angina. Report of Five Cases Including One Autopsy. PMID- 17862253 TI - III. Tumors of the Breast in Childhood. PMID- 17862254 TI - IV. Biliary Calculus Weighing Two and One Half Ounces Removed from the Common Duct. PMID- 17862255 TI - V. Acute Dilatation of the Stomach Complicating Typhoid Fever. PMID- 17862256 TI - VI. Acute Haematogenous Infection of One Kidney in Persons Apparently Well. A Report of Eight Cases. PMID- 17862257 TI - VII. Contribution to Renal and Ureteral Surgery. PMID- 17862258 TI - VIII. Arthroplasty for Complete Ankylosis of the Elbow. Result One Year and a Half After Operation. PMID- 17862259 TI - IX. Some Surgical Conditions in the Knee-Joint. PMID- 17862260 TI - X. The Operative Treatment of Fracture of the Neck of the Femur in Adults. PMID- 17862262 TI - XII. Non-Tuberculous Osteomyelitis of the Os Calcis. PMID- 17862261 TI - XI. The Conservative Treatment of Fractures of the Femur: Note on the End-Results of Sixty-One Fractures of the Femur Conservatively Treated. PMID- 17862264 TI - XIV. Surgical Progress Excerps from Transactions of the German Congress of Surgery, 1908. PMID- 17862263 TI - XIII. Silverized Catgut-The Argyrol Method. The Use of Argyrol in its Preparation. PMID- 17862265 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , June 1, 1908: Stated Meeting. PMID- 17862266 TI - I. Invagination of Meckel's Diverticulum: Report of a Case and a Study of the Literature. PMID- 17862267 TI - II. Peritonitis in Children from Unknown Sites of Infection. PMID- 17862268 TI - III. Diffuse Septic Peritonitis Due to Appendicitis: With Reference to After Treatment with Postural Drainage. PMID- 17862269 TI - IV. The Interlocking Suture. PMID- 17862270 TI - V. Primary Sarcoma of the Peritoneum. PMID- 17862271 TI - VI. Gunshot Wound of Abdomen, Complicated with Pregnancy. PMID- 17862272 TI - VII. Appendicitis and Tetany. PMID- 17862273 TI - VIII. Harrington's Operation of Intraperitoneal Cystotomy: With Report of Four Cases. PMID- 17862275 TI - X. A Further Report of the Operative Treatment of Acute Gonorrhoeal Epididymitis. PMID- 17862274 TI - IX. Simultaneous Ligation of Both External Iliac Arteries for Secondary Hemorrhage. PMID- 17862276 TI - XI. Finger Enucleation of the Tonsil: A Method for the Removal of Whole Tonsils in Children. PMID- 17862278 TI - XIII. Arteriovenous Anastomosis for Gangrene: The Report of a Third Case. PMID- 17862277 TI - XII. Blastomycosis of the Spine: Double Lesion: Two Operations: Recovery. PMID- 17862280 TI - XV. Skin Grafting of the Heel. PMID- 17862279 TI - XIV. A Modification of the Gritti Amputation. PMID- 17862281 TI - XVI. Some Deformities of the Hand. PMID- 17862282 TI - XVII. Fracture of the Os Magnum. PMID- 17862283 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 14, 1908: Stated Meeting. PMID- 17862284 TI - I. Studies in Cancer-Historical and Critical. PMID- 17862286 TI - X. A Modification of the Bradford Frame for the Treatment by Suspension of Fractures of the Femur in Young Children. PMID- 17862285 TI - IX. Giant-cell Sarcoma of Forearm. PMID- 17862287 TI - XI Portable Traction Apparatus for Treating Fractures of the Femur and for Various Orthopaedic Operations. PMID- 17862288 TI - XII. Intestinal Intussusception Complicating Typhoid Fever: Report of a Case of Intestinal Intussusception with Mesenteric Thrombi Occurring During First Week of Typhoid Fever. PMID- 17862289 TI - XIII. A Modified Crile Tube for the Direct Transfusion of Blood. PMID- 17862290 TI - XIV. Surgical Progress Reports on Cancer of Kidney and Bladder from the Second Congress of International Society of Surgery, September, 1908. PMID- 17862291 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 28, 1908: Stated Meeting. PMID- 17862293 TI - II. The Serum Reaction in Cancer: Report from the Pathological Laboratory of the Skin and Cancer Hospital of New York City. PMID- 17862292 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , October 5, 1908: Stated Meeting. PMID- 17862294 TI - III. Newer Conceptions of Operative Technic in Cleft Palate and Harelip. PMID- 17862295 TI - IV. Aberrant Thyroid: Report of a Case; from the Clinic of Professor Kanavel at the Chicago Post-Graduate Hospital. PMID- 17862296 TI - V. Suppurative Pericarditis. PMID- 17862297 TI - VI. Restoration of the Perineal Portion of the Urethra After Destruction by Fracture of the Pelvis. PMID- 17862298 TI - VII. Catheter Fever: Report of a Case with a Rapidly Fatal Termination. PMID- 17862299 TI - VIII. Cruroscrotal Hernia: An Entero-Epiplocele, with the Spermatic Cord in the Femoral Canal, the Testicle in the Scrotum and an Absence of the Inguinal Canal. PMID- 17862300 TI - I. Intestinal Obstruction Due to Volvulus or Adbesions of the Sigmoid Colon, with a Report of Five Cases, and a Study of the Etiological Factors: One Case of Recurrent Volvulus of Sixteen Years' Duration, Thirty-Two Attacks, Cured by Resection; Second, an Observation at Operation, of Acute Volvulus Seven Hours After the Onset of Symptoms. PMID- 17862302 TI - III. The Prevention of Intestinal Obstruction Following Operation for Appendicitis. PMID- 17862301 TI - II. The Value of the Cammidge Reaction in the Diagnosis of Pancreatic Disease: From the Private Laboratory of Dr. John H. Musser. PMID- 17862303 TI - IV. Accidents in Hernia Operations: With Especial Reference to the Vessels. PMID- 17862304 TI - V. A New Cystoscope for Catheterizing the Ureters by the Indirect Method. PMID- 17862305 TI - VI. A New Indirect Irrigating Observation and Double Catheterizing Cystoscope. PMID- 17862306 TI - VII. Complete Denudation of the Penis. PMID- 17862307 TI - VIII. The Operative Technic of Carcinoma of the Penis. PMID- 17862308 TI - IX. Carbolic Acid Gangrene of the Finger. PMID- 17862309 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , November 11, 1908: Stated Meeting. PMID- 17862310 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , November 25, 1908: Stated Meeting. PMID- 17862312 TI - Vas Deferens Anastomosis. PMID- 17862311 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , November 2, 1908: Stated Meeting. PMID- 17862313 TI - I. The Intra-abdominal Administration of Oxygen: A Further Contribution, with Reports of Additional Cases. PMID- 17862314 TI - II. Plastic Surgery of Blood-vessels and Direct Transfusion of Blood. PMID- 17862315 TI - III. Nerve Involvement in the Ischaemic Paralysis and Contracture of Volkmann. PMID- 17862316 TI - IV. Operating upon the Cranial Vault. PMID- 17862317 TI - V. The Surgical Treatment of Internal Hydrocephalus. PMID- 17862318 TI - VI. Operations Involving Free Opening of the Thorax: Inflation of the Collapsed Lung with Oxygen at the Moment of Closing the Chest Cavity after Operation. PMID- 17862319 TI - VII. The Value of the Leucocyte and Differential Counts in Appendicitis. PMID- 17862320 TI - VIII. Typhoid Fever with Multiple Perforations, Repeated Operations Followed by Ultimate Recovery. PMID- 17862321 TI - IX. Angeiorrhaphy: Suture of a Double Stab Wound of the Femoral Artery and Vein. PMID- 17862322 TI - X. Perforating Wound of the Knee-joint: A Case in which a Piece of Steel was Driven Through the Knee-Joint, Fracturing the Patella and Cutting a Chip of Bone out of the External Condyle; Functional Result Perfect. PMID- 17862323 TI - XI. An Apparatus for the Introduction of Salines into the Rectum. PMID- 17862324 TI - XII. The Sitting Posture; Its Postoperative and Other Uses: With a Description of a Bed for Holding a Patient in this Position. PMID- 17862325 TI - XIII. A Method of Splinting Skin Grafts. PMID- 17862326 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , December 9, 1908: Stated Meeting. PMID- 17862327 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , December 7, 1908: Stated Meeting. PMID- 17862328 TI - Intestinal Intussusception Complicating Typhoid Fever. PMID- 17862329 TI - I. An Analytical and Statistical Review of One Thousand Cases of Head Injury. PMID- 17862330 TI - II. The Rational Treatment of Non-malignant and Border-line Tumors of the Breast. PMID- 17862331 TI - III. Mesocolic or Retrogastric Hernia. PMID- 17862332 TI - IV. Inguinal Hernia of the Caecum. PMID- 17862333 TI - V. Hernia of the Vermiform Appendix, with an Account of Four Cases. PMID- 17862334 TI - VI. Cystic Dilatation of the Vermiform Appendix: From the Pathologic Laboratory of the Philadelphia Polyclinic Hospital and College. PMID- 17862335 TI - VII. Prostatic Abscess; Observations upon the Pathology and Operative Treatment. PMID- 17862337 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , January 27, 1909: Stated Meeting. PMID- 17862336 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , January 13, 1909: Stated Meeting. PMID- 17862338 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , January 4, 1909: Stated Meeting. PMID- 17862339 TI - An Interlocking Suture. PMID- 17862340 TI - Technic of Tying off the Mesentery in Doing a Resection of the Intestine. PMID- 17862341 TI - I. An Analytical and Statistical Review of One Thousand Cases of Head Injury. PMID- 17862342 TI - II. Osteosarcoma of the Mandible. PMID- 17862343 TI - III. Congenital Mesenteric Cysts. PMID- 17862344 TI - IV. On "Essential Haematuria" and "Nephralgia.": With Remarks on the Technic of Nephrotomy. PMID- 17862345 TI - V. Renal Varix-Angiomatous Disease of the Papillae Renales. PMID- 17862346 TI - VI. Observations on Renal and Ureteral Calculi. PMID- 17862347 TI - VII. Procidentia Recti; Treatment by Excision. PMID- 17862348 TI - VIII. Intestinal Anastomosis by Invagination. PMID- 17862349 TI - IX. Excision of the Shoulder Joint.-A Study of Nineteen Excisions of the Shoulder Joint. PMID- 17862350 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , February 10, 1909: Stated Meeting. PMID- 17862351 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , February 1, 1909: Stated Meeting. PMID- 17862352 TI - I. The Surgical Treatment of Locomotor Ataxia. PMID- 17862353 TI - II. Traumatic Asphyxia: With Report of a Case. PMID- 17862355 TI - IV. Ligation of the External Carotids: With Reports of Seven Ligations in Four Cases. PMID- 17862354 TI - III. A Case of Stasis Cyanosis following an Epileptic Seizure, Simulating Traumatic Asphyxia. PMID- 17862356 TI - V. Cystitis and Ulceration of the Bladder in Women. PMID- 17862357 TI - VI. Tuberculosis of the Bladder. PMID- 17862358 TI - VII. The Surgical Treatment of Tuberculosis of the Epididymis and Testicle. PMID- 17862359 TI - VIII. Removal of a Gauze Sponge from the Scrotum, Two and a Half Years After an Operation for Double Inguinal Hernia: Including a Report of Five Cases in which Foreign Bodies were Left in Operative Wounds Other than in the Peritoneal Cavity. PMID- 17862360 TI - IX. Bone Transference: Report of a Case of Operation after the Method of Huntington. PMID- 17862361 TI - X. Report of Saturday Surgical Clinics for Students: Held at the German Hospital of Philadelphia, 1907 and 1908. PMID- 17862363 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , February 24, 1909: Stated Meeting. PMID- 17862362 TI - XI. The Volunteer Military Surgeon. PMID- 17862365 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , March 1, 1909: Stated Meeting. PMID- 17862364 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , March 10, 1909: Stated Meeting. PMID- 17862366 TI - I. End Results After Total Excision of the Scapula for Sarcoma: With Statistical Tables. PMID- 17862367 TI - XI. The Operative Treatment of Heart Wounds: Report of a Case of Wound of the Right Auricle; Suture; Recovery. Tabulation of 158 Cases of Sutured Heart Wounds. PMID- 17862368 TI - XII. The Operative Treatment of Tuberculosis of the Lungs. PMID- 17862369 TI - XIII. Resection of Ribs, with External Pressure in Apical Tuberculosis. PMID- 17862370 TI - XIV. The Treatment of Fistulae and Abscesses Following Operations for Empyema of the Thorax. PMID- 17862371 TI - XV. Empyema Thoracis. PMID- 17862372 TI - XVI. OEsophagogastrostomy after Intrathoracic Resection of the OEsophagus. PMID- 17862373 TI - XVII. Chronic Intestinal Stasis. PMID- 17862374 TI - XVIII. Surgery of the Large Intestine: With a Review of One Hundred Resections. PMID- 17862376 TI - II. The Old and New in Surgery. PMID- 17862375 TI - XIX. Distortion of the Mesentery and Its Relation to Intestinal Obstruction. PMID- 17862377 TI - XX. I. Strangulated Retroperitoneal Hernia II. Interparietal Ventral Hernia at McBurney's Point. PMID- 17862378 TI - XXI. Vesico-Intestinal Fistulae. PMID- 17862379 TI - XXII. Fibroid Tumors of the Uterus demanding Operation. PMID- 17862380 TI - XXIII. Resection of the Sciatic Nerve: Neuroplasty: End Results. PMID- 17862381 TI - XXIV. Inequalities of the Right and Left Femora. PMID- 17862382 TI - XXV. The Transportation of Skin Flaps. PMID- 17862384 TI - TRANSACTIONS OF THE AMERICAN SURGICAL ASSOCIATION. , June 3, 4, 5, 1909: Annual Meeting. PMID- 17862383 TI - XXVI. Massive Keloid of Face and Hands. PMID- 17862385 TI - III. Sudden Death. PMID- 17862386 TI - IV. Treatment of Tetanus by Chloretone. PMID- 17862387 TI - V. Aneurisms in Young People. PMID- 17862388 TI - VI. Gunshot Injury of the Brain: With Late Manifestations After Immediate Recovery. PMID- 17862389 TI - VII. Complete Detachment of the Facial Bones: Recovery. Condition at the End of Fourteen Months. PMID- 17862390 TI - VIII. The Parathyroid Question. PMID- 17862391 TI - IX. The Histopathology of Goitre: Based Upon the Microscopical Study of Over Fifty Cases of Thyroidectomy, with Histories of the Most Important. PMID- 17862392 TI - X. Excision of the Larynx for Carcinoma. PMID- 17862393 TI - I. Jejunal and Gastrojejunal Ulcer following Gastrojejunostomy: With Notes of Two Cases, in One of which Gastric Analyses were Made before and after Operation for Jejunal Ulcer, with an Abstract of Sixty-One Other Cases, and Observations Thereon. PMID- 17862395 TI - III. A Case of Pistol-Shot Wound of the Axillary Artery: Ligation of First Portion: Recovery. PMID- 17862394 TI - II. Surgical Procedures Designed for the Relief of Pulmonary Tuberculosis. PMID- 17862396 TI - IV. The Treatment of Diffuse Septic Peritonitis. PMID- 17862398 TI - VI. Large Sliding Hernias of the Sigmoid: With a Description of an Operation for their Relief. PMID- 17862397 TI - V. Volvulus of Giant Sigmoid Colon: Recurrent Attacks of Acute Obstruction; Relief by New Method. PMID- 17862399 TI - VII. The Fat Appendix. PMID- 17862401 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , April 14, 1909: Stated Meeting. PMID- 17862400 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , March 24, 1909: Stated Meeting. PMID- 17862402 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , April 5, 1909: Stated Meeting. PMID- 17862403 TI - Surgical Treatment of Locomotor Ataxia. PMID- 17862404 TI - A New Method of Nephropexy. PMID- 17862405 TI - I. An Analytical and Statistical Review of One Thousand Cases of Head Injury. PMID- 17862406 TI - II. Skin Grafting at the Johns Hopkins Hospital. PMID- 17862408 TI - IV. Hour-Glass Stomach. PMID- 17862407 TI - III. Cyst of the Round Ligament of the Liver. PMID- 17862409 TI - V. Diagnosis and Treatment of Carcinoma of the Caecum: With a Report of Two Cases Treated by Resection of the Caecum. PMID- 17862410 TI - VI. Resection of the Colon for Cancer and Tuberculosis. PMID- 17862411 TI - VII. Large Phagedenic Ulcer of the Abdomen. PMID- 17862412 TI - VIII. Inguinal Hernia in the Female. PMID- 17862413 TI - IX. Surgical Aspects of Chronic Hypertrophic Arthritis. PMID- 17862414 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , April 28, 1909: Stated Meeting. PMID- 17862416 TI - Intestinal Anastomosis by Invagination. PMID- 17862415 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , May 3, 1909: Stated Meeting. PMID- 17862417 TI - I. An Analytical and Statistical Review of One Thousand Cases of Head Injury. PMID- 17862418 TI - II. Injuries of the Kidneys. PMID- 17862419 TI - III. The Surgical Conception of Pancreatitis. PMID- 17862420 TI - IV. The Advantage of Simplicity in Operations for Appendicitis: A Report Based on 110 Consecutive Operations Without Mortality. PMID- 17862422 TI - VI. Intravenous Local Anaesthesia. PMID- 17862421 TI - V. An Irrigating Sound of the Standard and Benique Type: Also an Irrigating Tunnelled and Grooved Sound for the Dilatation Treatment of Stricture of the Male Urethra. PMID- 17862424 TI - VIII. The "Open-Seat" Pelvic Binder: A Practical Bandage for Operations on the Scrotum and Testes and Ilio-Inguinal Region. PMID- 17862423 TI - VII. A Modification of the Crile Transfusion Cannula. PMID- 17862425 TI - IX. Note on Silver Foil in Surgery. PMID- 17862426 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , May 12, 1909: Stated Meeting. PMID- 17862427 TI - Total Excision of the Scapula for Sarcoma. PMID- 17862428 TI - I. A Study of Burns Involving the Periosteum of the Vault of the Skull. PMID- 17862430 TI - III. The Closure of the Wound after the Radical Amputation of the Breast. PMID- 17862429 TI - II. The Operative Treatment of Cancer of the Larynx. PMID- 17862431 TI - IV. The Postoperative Treatment in Cases of Typhoid Perforation: Report of Four Consecutive Cases Operated Upon with Recovery. PMID- 17862432 TI - V. Spontaneous Rupture of the Spleen in the Course of Typhoid Fever. PMID- 17862433 TI - VI. Ileocolic Intussusception in an Adult: With Remarks on the Method of Formation and Growth of this Variety of Intussusception. PMID- 17862434 TI - VII. A Very Early Form of Renal Tuberculosis Revealed by Nephrectomy. PMID- 17862435 TI - VIII. The Surgical Treatment of Non-Resilient Diverticula of the Bladder. PMID- 17862436 TI - IX. Fibrolymphosarcomata of Both Ureters Metastatic to a Primary Lymphosarcomata of the Anterior Mediastinum of Thymus Origin. PMID- 17862437 TI - X. Congenital Unilateral Absence of the Urogenital System. PMID- 17862438 TI - XI. Peri-Ureteral Pelvic Phleboliths. PMID- 17862439 TI - XII. Cyst of the Prostatic Urethra. PMID- 17862441 TI - XIV. A New Operation for Ingrown Toe-Nail. PMID- 17862440 TI - XIII. Interilio-Abdominal Amputation: With Report of a Case. PMID- 17862442 TI - XV. The Treatment of Gonorrhoeal Arthritis with Vaccines made from the Gonococcus: A Review of Fifty-One Cases. PMID- 17862443 TI - Torsion of Spermatic Cord. PMID- 17862444 TI - III. Partial Hypophysectomy for Acromegaly: With Remarks on the Function of the Hypophysis. PMID- 17862445 TI - IV. Ligation of the Thyroid Vessels in Cases of Hyperthyroidism. PMID- 17862446 TI - V. The Significance of Thyroidism and its Relation to Goitre. PMID- 17862447 TI - VI. Treatment of Dry Arthritis with Injection of Vaseline. PMID- 17862449 TI - VIII. Some Considerations upon High Amputation of the Rectum. PMID- 17862448 TI - VII. Lymphatics of the Colon: With Special Reference to the Operative Treatment of Cancer of the Colon. PMID- 17862450 TI - IX. Principles of a Radical Treatment for Proctosigmoiditis. PMID- 17862451 TI - X. The Operative Treatment of Fractures. PMID- 17862452 TI - XI. A Clamp for the Fixation of Ununited Fractures. PMID- 17862453 TI - XII. Musculospiral Paralysis Complicating Fracture of the Humerus: An Analysis of the Cases at the Massachusetts General Hospital. PMID- 17862454 TI - XIII. Note on Partial Nephrectomy. PMID- 17862455 TI - Partial Resection of the Bladder for Malignant Tumor by the Transperitoneal Route. PMID- 17862456 TI - XV. Cancer of the Prostate: A Clinical, Pathological and Post-Operative Analysis of 111 Cases. PMID- 17862458 TI - XVII. Pancreato-enterostomy and Pancreatectomy: A Preliminary Report. PMID- 17862457 TI - XVI. Acute Haemorrhagic Pancreatitis: Report of a Case Subjected to Operation Terminating in Recovery. PMID- 17862459 TI - XVIII. A Disease of the Gall-Bladder requiring Cholecystectomy. PMID- 17862460 TI - XIX. Transduodenal Choledochotomy: Report of a Case, with Comments on the Clinical and Operative Features. PMID- 17862461 TI - XX. Ileus due to Meckel's Diverticulum. PMID- 17862462 TI - XXI. Diffuse Peritonitis. PMID- 17862463 TI - XXII. Appendicostomy in Conditions of Acute Peritonitis. PMID- 17862464 TI - XXIII. The Appendix Vermiformis: A Note on its Physiology and Surgery. PMID- 17862465 TI - Beginnings of the : Annals of Surgery. PMID- 17862466 TI - I. Intrahuman Bone Grafting and Reimplantation of Bone. PMID- 17862467 TI - II. Derangements of the Knee: Based Upon a Personal Experience of Over Five Hundred Operations. PMID- 17862468 TI - I. The Blood in Surgery: A Historical and Critical Study. PMID- 17862469 TI - X. Paralytic Ileus as a Sequel of Fractured Ribs. PMID- 17862471 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 13, 1909: Stated Meeting. PMID- 17862470 TI - XI. Fibrinous Calculi in the Kidney. PMID- 17862472 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , October 27, 1909: Stated Meeting. PMID- 17862474 TI - Examinations of Hospital Internes. PMID- 17862473 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , October 4, 1909: Stated Meeting. PMID- 17862476 TI - II. The Two-stage Principle in Operative Surgery. PMID- 17862475 TI - Technic for a Temporary Enterostomy. PMID- 17862477 TI - III. The Effect of Scarlet Red, in Various Combinations, upon the Epitheliation of Granulating Surfaces. PMID- 17862478 TI - IV. Chloroma of the Jaws. PMID- 17862479 TI - V. Cervical Subcutaneous Cavernous Haemangeioma: With Report of Two Cases. PMID- 17862480 TI - VI. Aneurism of the Internal Carotid Treated by Matas' Method. PMID- 17862482 TI - VIII. The Surgical Treatment of Empyema Thoracis. PMID- 17862481 TI - VII. An Operation for Paralytic Shoulder Joint Due to Infantile Paralysis. PMID- 17862483 TI - IX. Studies of Pancreatitis and the Pancreatic Reaction of Cammidge. PMID- 17862484 TI - I. The Results of "Specific" Remedies in Diseased States Accompanied by Hypertrophy of the Thyroid. PMID- 17862485 TI - II. Suggestions for the Operative Correction of Syphilitic and Other Deformities of the Nose. PMID- 17862487 TI - IV. Traumatic Lesions of the Atlas and Axis. PMID- 17862486 TI - III. Rhinoplasty by Means of One of the Fingers. PMID- 17862488 TI - V. Atlo - Axoid Fracture - Dislocation. PMID- 17862489 TI - VI. Malignant Degeneration of Benign Diseases of the Breast. PMID- 17862490 TI - VII. Acute Intussusception of the Ileum with Volvulus. PMID- 17862491 TI - VIII. A Method of Anastomosis between Sigmoid and Rectum. PMID- 17862492 TI - IX. Excision of the Rectum for Cancer by the Perineal Route. PMID- 17862493 TI - X. The Treatment of Gangrene of the Foot by Arterial Anastomosis. PMID- 17862495 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , November 24, 1909: Stated Meetings. PMID- 17862494 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , November 10 1909: Stated Meetings. PMID- 17862496 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , November 1, 1909: Stated Meeting. PMID- 17862497 TI - I. An X-Ray Study of Bone Atrophy. PMID- 17862498 TI - II. The Radical Extirpation of Pharyngo-OEsophageal Pressure Diverticula. PMID- 17862500 TI - IV. Functional Diagnosis of Renal Disease, especially by Experimental Polyuria. PMID- 17862499 TI - III. Investigations Concerning the Technic of Lung Resection with the Application of Both Forms of Differential Pressure. PMID- 17862501 TI - V. Infections of the Urinary Tract due to Bacillus Coli and Allied Organisms: Further Observations on the Treatment of Acute and Chronic Conditions. PMID- 17862503 TI - VII. Perinephric Abscess: A Clinical Contribution Based on Thirty-Six Cases. PMID- 17862502 TI - VI. Intraperitoneal Division of One Ureter: A Clinical and Experimental Study. PMID- 17862504 TI - VIII. Genital Canal Block following Neisser Coccus Infection. PMID- 17862505 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , December 6, 1909: Stated Meeting. PMID- 17862506 TI - I. Stovaine Spinal Anaesthesia: A Report of Twenty Cases. PMID- 17862507 TI - II. Terminal Arterial Anaesthesia. PMID- 17862508 TI - III. Anaesthesia by Colonic Absorption of Ether. PMID- 17862509 TI - IV. Pus in the Abdominal Cavity. PMID- 17862510 TI - V. The Treatment of Diffuse Progressive Free Peritonitis: A Study of Six Hundred and Nine Cases. PMID- 17862511 TI - VI. Bone Plastic for Skull Defects. PMID- 17862512 TI - VII. Ping-Pong-Ball Indentation of the Skull Without Fracture. PMID- 17862513 TI - VIII. Tuberculosis of the Lip. PMID- 17862514 TI - IX. Suture of the Recurrent Laryngeal Nerve: With Report of a Case. PMID- 17862515 TI - X. Unilateral Laminectomy. PMID- 17862516 TI - XI. Deformities of the Renal Pelvis. PMID- 17862517 TI - XII. Angioma of Papillae of the Kidney: Report of Three Cases of Persistent Haematuria Relieved by Conservative Operation. PMID- 17862519 TI - XIV. The Treatment of Syphilis by Hypodermic Injections of Salicylate of Mercury. PMID- 17862518 TI - XIII. Combined Cystoscopic and Roentgenographic Examination of the Kidneys and Ureter. PMID- 17862520 TI - XV. Plastic Operation for the Relief of an Incurvation of the Penis. PMID- 17862522 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , December 8, 1909: Stated Meeting. PMID- 17862521 TI - XVI. The Principle of the Teale Flap applied to Amputation of the Penis. PMID- 17862523 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , January 3, 1910: Stated Meeting. PMID- 17862524 TI - I. The Relation of Trauma to Cancer Formation. PMID- 17862525 TI - II. Skeletal Carcinomatosis: With Report of a Case. PMID- 17862526 TI - III. A Tourniquet for the Control of Hemorrhage from the Scalp during Osteoplastic Resection of the Skull. PMID- 17862528 TI - V. Pancreatic Hemorrhage and Acute Pancreatitis. PMID- 17862527 TI - IV. The Pathology of the Gall-bladder and some Associated Lesions: A Study of Specimens from 365 Cholecystectomies. PMID- 17862529 TI - VI. Retroperitoneal Hernia of the Pericaecal Type: Report of a Case with References to the Literature. PMID- 17862530 TI - VII. An Operation for Umbilical Hernia. PMID- 17862531 TI - VIII. The Diagnosis of Typhoid Perforation: With Report of Cases. PMID- 17862533 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , January 12, 1910: Stated Meeting. PMID- 17862532 TI - IX. Treatment of Chronic Tuberculous Sinuses by Beck's Bismuth-Vaseline Paste Injections. PMID- 17862534 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , February 7, 1910: Stated Meeting. PMID- 17862535 TI - I. Note on the Neuropathologic Cytology of Anaemia, Infections, Graves's Disease, and Surgical Shock. PMID- 17862536 TI - II. Therapy by Bacterins and Tuberculins in Mixed Suppurative Bone and Joint Disease. PMID- 17862537 TI - III. The Study of the Etiology of Cancer Based on Clinical Statistics. PMID- 17862538 TI - IV. On the Simulation of Neoplasms by Inflammatory Processes. PMID- 17862539 TI - V. Prognosis and Operative Treatment of Fracture of the Base of the Skull: Based on an Analysis of 190 Cases. PMID- 17862540 TI - VI. Diagnosis and Surgical Treatment of OEsophageal Diverticula: Report of Eight Cases. PMID- 17862542 TI - VIII. Hepaticoduodenal Anastomosis. PMID- 17862541 TI - VII. Resection of the Pancreas: Report of a Case. PMID- 17862543 TI - IX. Wandering Spleen: Report of a Case with Twisted Pedicle, Producing a Tumor in the Pelvis. PMID- 17862544 TI - X. The Separation of the Colon from its Mesentery: A Clinical and Experimental Study. PMID- 17862545 TI - XI. Congestion of the Lower Lobe of the Right Lung an Early Symptom in Appendicitis: A Clinical Note. PMID- 17862546 TI - XII. Removal of the Rectum for Cancer: Statistical Report of 120 Cases. PMID- 17862547 TI - XIII. Choriocarcinoma: Report of a Case Occurring in a Patient with an Infantile Uterus. PMID- 17862548 TI - XIV. On Momburg's Method of Artificial Anaemia by Suprapelvic Constriction. PMID- 17862550 TI - XVI. Operations upon the Appendix: Analysis of 1411 Operations Performed at the Presbyterian Hospital, New York. PMID- 17862549 TI - XV. Old Irreducible Dislocations of the Shoulder Joint. PMID- 17862551 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , February 9, 1910: Stated Meeting. PMID- 17862552 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , February 23, 1910: Stated Meeting. PMID- 17862553 TI - I. Operations upon the Hypophysis. PMID- 17862554 TI - X. Abnormal Position of the Duodenum. PMID- 17862555 TI - XI. End-to-End Intestinal Anastomosis by the Invagination Method. PMID- 17862556 TI - TRANSACTIONS OF THE AMERICAN SURGICAL ASSOCIATION , May 3, 4, and 5, 1910: Annual Meeting. PMID- 17862557 TI - II. Tumor of the Hypophysis (with Infantilism): Operation-Recovery (Preliminary Report). PMID- 17862558 TI - III. Clinical Experiences with Intratracheal Insufflation (Meltzer), with Remarks upon the Value of the Method for Thoracic Surgery. PMID- 17862559 TI - IV. The First Case of Thoracotomy in a Human Being under Anaesthesia by Intratracheal Insufflation. PMID- 17862560 TI - V. Some Observations Regarding Thoracic Surgery on Human Beings. PMID- 17862561 TI - VI. Artificial Respiration and Intrathoracic OEsophageal Surgery. PMID- 17862562 TI - VII. Cancer of the OEsophagus and Cardia: A Description of an Operation for its Removal by the Transthoracic Route Under Conditions of Differential Pressure. PMID- 17862563 TI - VIII. On the Experimental Surgery of the Thoracic Aorta and Heart. PMID- 17862564 TI - IX. Treatment of Wounds of the Heart: With Report of Two Cases. PMID- 17862565 TI - I. Benign Bone Cysts, Ostitis Fibrosa, Giant-Cell Sarcoma and Bone Aneurism of the Long Pipe Bones: A Clinical and Pathological Study with the Conclusion that Conservative Treatment is Justifiable. PMID- 17862566 TI - II. Neoplasms and Other Tumors Involving the Maxillary Bones. PMID- 17862567 TI - III. Fracture of the Head and Neck of the Radius. PMID- 17862568 TI - IV. Backward Dislocation of the Upper End of the Ulna: Old, Complete Dislocation of the Ulna Alone, with Rotation Around the Head of the Radius. Operation: Good Result. PMID- 17862570 TI - VI. Spontaneous Forward Dislocation of the Wrist-Joint: Madelung's Deformity. PMID- 17862569 TI - V. Autoplastic Transplantation of Bone. PMID- 17862571 TI - VII. The Cystoscopic Examination in Renal Tuberculosis. PMID- 17862572 TI - VIII. Cystic Disease of the Breast. PMID- 17862573 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , March 9, 1910: Stated Meeting. PMID- 17862575 TI - Suture of the Recurrent Laryngeal Nerve. PMID- 17862574 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , March 7, 1910: Stated Meeting. PMID- 17862576 TI - I. A Contribution to the Symptomatology and Surgical Treatment of Spinal Cord Tumors. PMID- 17862578 TI - III. Transgastric Jejunal Feeding: After Gastro-Enterostomy Combined with Gastrostomy. Tested in a Case of Arteriomesenteric Ileus. PMID- 17862577 TI - II. Intestinal Lesions Produced by Blunt Force: A Report of Four Cases. PMID- 17862579 TI - IV. The Proposed Fistulo-enterostomy of Von Stubenranch. PMID- 17862580 TI - V. Permanent Colostomy: An Improved Original Operative Method. PMID- 17862581 TI - VI. Myeloma of the Long Bones. PMID- 17862582 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , March 23, 1910: Stated Meeting. PMID- 17862583 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , April 13, 1910: Stated Meeting. PMID- 17862584 TI - I. Transfusion by Carrel's End-to-end Suture Method: With Report of Cases. PMID- 17862586 TI - III. Graft of the Vena Cava on the Abdominal Aorta. PMID- 17862585 TI - II. Blood Transfusion in Haemophilia. PMID- 17862587 TI - IV. A Suggestion for the Treatment of Air Embolism. PMID- 17862588 TI - V. Preservation of the Submaxillary Branch of the Facial Nerve in Operations on the Neck. PMID- 17862589 TI - VI. Anaesthol Poisoning, causing Acute Yellow Atrophy of Liver after Operation for Ileocolic Intussusception. PMID- 17862590 TI - VII. The Surgical Aspect of Epulis and Sarcoma of the Jaw. PMID- 17862591 TI - VIII. The Use of Differential Pressure in the Treatment of Empyema. PMID- 17862592 TI - IX. Primary Sarcoma of the Stomach: With Report of Two Cases. PMID- 17862593 TI - X. The Function of the Appendix and the Origin of Appendicitis. PMID- 17862594 TI - XI. A Simple Method of Suturing all Hollow Viscera. PMID- 17862595 TI - XII. The Rectosigmoidal Arterial Anastomosis: Its Importance in the Treatment of Carcinoma High in the Rectum. PMID- 17862597 TI - XIV. Plastic Repair of the Thumb. PMID- 17862596 TI - XIII. The Bone Metastases of Hypernephroma: A Completed Record of a Case with Solitary Bone Metastasis. PMID- 17862598 TI - XV. Wright's Solution of Sodium Citrate and Sodium Chloride for Drainage. PMID- 17862600 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , April 27, 1910: Stated Meeting. PMID- 17862599 TI - XVI. The Relation of the Ductless Glands to Surgery. PMID- 17862602 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , April 25, 1910: Annual Meeting. PMID- 17862601 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , April 4, 1910: Stated Meeting. PMID- 17862603 TI - I. Atony of the Bladder without Obstruction or Signs of Organic Nervous Diseases. PMID- 17862604 TI - II. Certain Congenital Strictures of the Ureter. PMID- 17862605 TI - III. Primary (Congenital) Hydronephrosis: Report of a Case with Remarks on the Treatment and Pathology. PMID- 17862606 TI - IV. Recent Developments in Pyelography. PMID- 17862607 TI - V. Note on the Removal of Carcinoma of the Fundus of the Urinary Bladder. PMID- 17862608 TI - VI. Intraperitoneal Cystotomy. PMID- 17862610 TI - VIII. Is the Sac of a Femoral Hernia of Congenital Origin, or Acquired? PMID- 17862609 TI - VII. A Chart to Aid in the Treatment of Cystitis by Distentions of the Bladder. PMID- 17862611 TI - IX. Silver Wire and Linen Thread for the Cure of Hernia. PMID- 17862613 TI - XI. The Control of Hemorrhage by Means of Forceps-Tourniquet in Major Amputations. PMID- 17862612 TI - X. A Pneumatic Tourniquet. PMID- 17862615 TI - TRANSACTIONS OF THE NEW YORK ACADEMY OF SURGERY , May 11, 1910: Stated Meeting. PMID- 17862614 TI - XII. Statistics about Fractures and Refractures of the Patella. PMID- 17862616 TI - I. The Treatment of Scalping Accidents: Report of Two Cases of Scalping by Machinery, with a Consideration of Scalping Accidents in General. PMID- 17862617 TI - II. The Responsibility of the Tonsil in Tuberculous Adenitis. PMID- 17862618 TI - III. Treatment of Tuberculous Glands of the Neck: A Study of 649 Operated Cases. PMID- 17862619 TI - IV. Metallic Foreign Bodies in a Bronchus: With a Report of Two Cases. PMID- 17862620 TI - V. Sarcoma of the Clavicle: End-Results following Total Excision. PMID- 17862621 TI - VI. Transgastric Excision of Calloused Ulcer of the Posterior Wall of the Body of the Stomach. PMID- 17862622 TI - VII. Relation between Appendicitis and Disturbance in the Gastro-duodeno-hepatico pancreatic Physiological System: A Report on the Examination of 5000 Appendices with a Comparative Study of the Pathology and Clinical Histories in 2000 Cases. PMID- 17862623 TI - VIII. The Technic of Appendicostomy: A Consideration of the Preservation of the Blood Supply of the Appendix in the Operation. PMID- 17862624 TI - IX. Anomalous Renal Arteries and Their Relation to Hydronephrosis. PMID- 17862625 TI - X. The Anatomy and Treatment of Undescended Testis; with Especial Reference to the Bevan Operation. PMID- 17862626 TI - XI. Resection of the Male Rectum for Cancer, by the Combined Method in Two Stages: First Stage Under Spinal Anaesthesia. PMID- 17862627 TI - XII. Fracture of the Tarsal Scaphoid: With a Report of Cases Treated by Operation. PMID- 17862628 TI - Charles Robert Bell Keetley, F.R.C.S. PMID- 17862629 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , October 12, 1910: Stated Meeting. PMID- 17862630 TI - I. Testing the Efficiency of the Collateral Circulation as a Preliminary to the Occlusion of the Great Surgical Arteries. PMID- 17862631 TI - VIII. Disinfection of the Skin by Tincture of Iodine. PMID- 17862632 TI - IX. Dry Iodine Catgut: A Further Contribution Upon the Subject, with an Improved Method of Preparation. PMID- 17862634 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , October 26, 1910: Stated Meeting. PMID- 17862633 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , October 26, 1910: Stated Meeting. PMID- 17862635 TI - II. Anatomical and Surgical Desiderata in the Exposure and Removal of the Pituitary Gland. PMID- 17862636 TI - III. The Treatment of X-Ray Ulcer. PMID- 17862637 TI - IV. Posterior Gastro-Enterostomy Three Years After Anterior Gastro-Enterostomy. PMID- 17862638 TI - V. Non-Prostatic Urinary Retention of the Senile Bladder. PMID- 17862640 TI - VII. Laceration of the Axillary Portion of the Capsule of the Shoulder-Joint as a Factor in the Etiology of Traumatic Combined Paralysis of the Upper Extremity. PMID- 17862639 TI - VI. Bone Abscess Treated with Moorhof's Bone Wax: A Report of Five Cases. PMID- 17862641 TI - I. Anaesthesia by the Intratracheal Insufflation of Air and Ether: A Description of the Technic of the Method and of a Portable Apparatus for Use in Man. PMID- 17862642 TI - II. Intussusception, with Special Reference to Adults. PMID- 17862643 TI - III. Diverticula of the Lower Bowel: Their Development and Relationship to Carcinoma. PMID- 17862644 TI - IV. On the Coincidence of Volvulus and Real or Simulated Strangulated Hernia. PMID- 17862646 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , November 9, 1910: Stated Meeting. PMID- 17862645 TI - V. The Restoration of Fecal Continence After Iliac Colostomy. PMID- 17862647 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , November 23, 1910: Stated Meeting. PMID- 17862648 TI - I. Parathyroid Implantation in the Treatment of Tetania Parathyreopriva. PMID- 17862649 TI - II. Gastrostomy as a Curative Measure per se in Non-Malignant Strictures of the OEsophagus. PMID- 17862651 TI - IV. The Importance of Preserving the Gall-Bladder in Operations upon the Gall Passages. PMID- 17862650 TI - III. Operative Treatment of Wounds of the Heart: With Report of a Recent Case of Bullet Wound of the Heart, Lung, and Liver. PMID- 17862652 TI - V. Retroperitoneal and Mesenteric Cysts of a Simple Nature. PMID- 17862653 TI - VI. The Abdominal Incision-The Removal of the Wedge of Skin and Fat to Facilitate Intra-Abdominal Operations. PMID- 17862654 TI - VII. Supernumerary Kidney Subject of Cystadenoma: Report of a Case Verified by Operation. PMID- 17862655 TI - VIII. The Damage Done to the Kidney by Operation. PMID- 17862657 TI - X. The Control of Urinary Drainage after Cystotomy. PMID- 17862656 TI - IX. Empyema of the Ureter. PMID- 17862658 TI - XI. The Technic of Median Perineal Prostatectomy. PMID- 17862659 TI - XII. An Operation for Stiffening the Knee-Joint: With Report of Cases from the Service of the New York Orthopaedic Hospital. PMID- 17862660 TI - XIII. Intussusception in the Adult: Two Cases, One Due to Multiple Adenomata of the Intestine, the Other to a Sarcoma of the Caecum: with a Discussion of Adenomata of the Intestine. PMID- 17862662 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , November 7, 1910: Stated Meeting. PMID- 17862661 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , December 14, 1910: Stated Meeting. PMID- 17862663 TI - I. Injury as a Causative Factor in Cancer. PMID- 17862664 TI - II. The Abduction Treatment of Fracture of the Neck of the Femur, with Especial Reference to the Advantages of the Semireclining Posture and Changes of Attitude in its Application to Elderly Subjects. PMID- 17862665 TI - III. Fractures of the Shaft of the Femur with Marked Displacement. PMID- 17862666 TI - IV. Fracture of the Patella: With a Report of Fifty-Six Cases. PMID- 17862667 TI - V. Nephroureterectomy: Description of a Simple and Improved Method. PMID- 17862668 TI - VI. Technic of the Operative Treatment of Appendicitis: With Especial Reference to the Treatment of Peritonitis. PMID- 17862670 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , January 11, 1911: Clinical Meeting. PMID- 17862669 TI - VII. Diverticulitis of the Rectum: A Report of Two Cases Operated Upon, One of them with Carcinomatous Degeneration. PMID- 17862671 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , January 25, 1911: Stated Meeting. PMID- 17862672 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , December 5, 1910: Stated Meeting. PMID- 17862673 TI - Cholelithiasis-Fourteen Thousand Calculi Removed at Operation. PMID- 17862675 TI - II. Injury as a Causative Factor in Cancer (Continued). PMID- 17862674 TI - I. Recent Advances in Pulmonary Surgery: With Special Reference to Differential Pressure and Wounds of the Lung. PMID- 17862676 TI - III. Acute Ulcer Peritonitis in Typhoid Fever: A Plea for its Earlier Recognition. PMID- 17862677 TI - IV. The Radical Cure of Femoral Hernia in the Aged. PMID- 17862678 TI - V. Acute Diverticulitis. PMID- 17862679 TI - VI. Appendicostomy to Safeguard the Excluded Colon in Lane's Operation for Chronic Intestinal Stasis. PMID- 17862680 TI - VII. Chylous Cysts of the Mesentery: Report of a Case; Operation; Recovery. PMID- 17862681 TI - VIII. Removal of the Ureter with a Tuberculous Kidney. PMID- 17862682 TI - IX. Results of the Use of the Moorhof Bone Plug in the Surgical Clinic of the University of Minnesota. PMID- 17862683 TI - X. A Further Note on the Clinical Use of Scarlet Red and its Component, Amidoazotoluol, in Stimulating the Epitheliation of Granulating Surfaces. PMID- 17862684 TI - XI. An Improved Device for Transfusion. PMID- 17862685 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , February 8, 1911: Stated Meeting. PMID- 17862686 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , January 16, 1911: Stated Meeting. PMID- 17862687 TI - I. Large Intrathoracic Cysts of the Thyroid Gland Causing Dyspnoea. PMID- 17862688 TI - II. Further Experiences with Anaesthesia by the Intratracheal Insufflation of Air and Ether. PMID- 17862689 TI - III. Laminectomy for Injury and Tumor of the Spinal Cord: With a Report of Six Cases. PMID- 17862690 TI - IV. Organoscopy: Cystoscopy of the Abdominal Cavity. PMID- 17862691 TI - V. The Treatment of Chronic Pancreatitis by Pancreatostomy: A New Operation. PMID- 17862692 TI - VI. Acute Hepatitis Simulating Stone in the Common Duct and Liver Abscess. PMID- 17862693 TI - VII. The Rational Treatment of Acute Appendicitis. PMID- 17862694 TI - VIII. Chronic Appendicitis: A Critical Study of Post-Operative End Results. PMID- 17862696 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , March 8, 1911: Stated Meeting. PMID- 17862695 TI - IX. Some Observations upon the Surgery of the Ureter: With a Brief Report of Thirty-One Cases. PMID- 17862697 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , March 22, 1911: Stated Meeting. PMID- 17862698 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , February 6, 1911: Stated Meeting. PMID- 17862699 TI - I. The Control of Bleeding in Operations for Brain Tumors: With the Description of Silver "Clips" for the Occlusion of Vessels Inaccessible to the Ligature. PMID- 17862700 TI - VIII. Some Modifications of Technic in the Surgery of the Gall-bladder and Bile ducts. PMID- 17862701 TI - IX. Mesenteric Cysts: With Report of a Case. PMID- 17862702 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , March 6, 1911: Stated Meeting. PMID- 17862703 TI - II. Subluxation of the Atlas: Report of Two Cases. PMID- 17862704 TI - III. The Treatment of Aneurism of the Abdominal Aorta by Partial Occlusion of the Aorta with the Metallic Band-the Effect upon the Urinary Secretion of this Procedure: A Report of Two Cases. PMID- 17862705 TI - IV. Negative Tension Drainage in the Treatment of Empyema. PMID- 17862706 TI - V. A Study of Carcinoma Mastitoides. PMID- 17862707 TI - VI. Epigastric Hernia. PMID- 17862708 TI - VII. The Pathology and Symptomatology of Gall-stones: Based Upon an Examination of Over 400 Cases Occurring at the London Hospital. PMID- 17862709 TI - I. A Case of Bilateral Temporomaxillary Ankylosis with an Original Method for Approaching the Temporomaxillary Articulation. PMID- 17862710 TI - II. Variations in the Anatomy of the Nasolachrymal Passages. PMID- 17862711 TI - III. The Nerve Supply of the Anterior Abdominal Wall and its Surgical Importance. PMID- 17862713 TI - V. Note on Penetrating Wounds of the Abdomen: Report of Cases Treated at the Macon, Ga., Hospital. PMID- 17862712 TI - IV. An Apparatus Designed to Facilitate Pelvic Surgery by Approximating the Abdominal Wound to the Depth of the Pelvis. PMID- 17862714 TI - VI. Congenital Hypertrophic Stenosis of the Pylorus. PMID- 17862715 TI - VII. A Simplified Gastro-enterostomy Clamp. PMID- 17862716 TI - VIII. The Pathology and Symptomatology of Gall-stones (Continued): Based Upon an Examination of Over 400 Cases Occurring at the London Hospital. PMID- 17862718 TI - X. Primary Ovarian Pregnancy. PMID- 17862717 TI - IX. A Double Gall-bladder Removed by Operation. PMID- 17862719 TI - XI. Concerning the Treatment of Tumors of the Urinary Bladder with the Oudin High frequency Current. PMID- 17862720 TI - XII. Approximation of the Ends of Fragments in Fractures with Contraction of the Attached Muscles. PMID- 17862721 TI - XIII. Simple Fracture of the Pisiform Bone. PMID- 17862722 TI - XIV. Germicidal and Osmotic Actions of Picric Acid. PMID- 17862723 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , April 12, 1911: Clinical Meeting. PMID- 17862724 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , April 26, 1911: Stated Meeting. PMID- 17862725 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , April 3, 1911: Stated Meeting. PMID- 17862726 TI - Vesicovaginal Fistula from Penetration of Floor of the Bladder by Horn of a Bull. PMID- 17862727 TI - I. Some Considerations in the Treatment of Fractures of the Long Bones. PMID- 17862729 TI - III. Extirpation of Tumors of Vomer through the Roof of the Mouth. PMID- 17862728 TI - II. The Treatment of Far-advanced Malignant Disease. PMID- 17862730 TI - IV. Pyloroptosis; Gastric Atony as the Original Cause of Neurasthenia, and its Cure. PMID- 17862731 TI - V. Ulcer of the Stomach and Duodenum with Special Reference to the End Results. PMID- 17862732 TI - VI. Obstruction of the Ileum by a Large Gall-stone; Enterostomy; Subsequent Cholecystectomy and Suture of Duodenum. PMID- 17862733 TI - VII. On Chronic Colitis and Pericolitis. PMID- 17862734 TI - VIII. Intussusception Caused by a Lipoma of the Descending Colon: Acute Intestinal Obstruction; Resection of the Colon. PMID- 17862735 TI - IX. Suppuration in Half of a Horseshoe Kidney. PMID- 17862736 TI - X. Surgical Treatment of Fistula in Ano without Mutilation of the Sphincter. PMID- 17862737 TI - XI. Everted Dorsal Dislocations of the Hip. PMID- 17862738 TI - XII. The Treatment of Oblique Fractures of the Tibia and other Bones by Means of External Clamps Inserted through Small Openings in the Skin. PMID- 17862739 TI - XIII. Acute Pneumococcus Infections of the Extremities. PMID- 17862740 TI - XIV. Dislocation of the Hip Complicated with Fracture of the Femur: Report of Two Cases. PMID- 17862742 TI - I. A Study of the Infections. PMID- 17862741 TI - TRANSACTIONS OF THE AMERICAN SURGICAL ASSOCIATION , June 19-21, 1911: Annual Meeting. PMID- 17862743 TI - II. The Anatomy of Spinal Puncture with Some Considerations on Technic and Paralytic Sequels. PMID- 17862744 TI - III. The Technic of End-to-End Arterial Anastomosis: With Report of a Case. PMID- 17862745 TI - IV. Lateral Vascular Anastomosis: An Improved Method. PMID- 17862746 TI - V. Some Recent Mechanical Aids to Hollow Visceral Anastomosis. PMID- 17862747 TI - VI. Ligation of the First Portion of the Left Subclavian Artery: With Report of a Recent Successful Case. PMID- 17862748 TI - VII. Fibro-Epithelial Tumors of the Mammary Gland. PMID- 17862749 TI - VIII. Intercostal Diaphragmatic Hernia: With Report of a Case. PMID- 17862751 TI - X. The Surgical Clinic of the Protestant Episcopal Hospital of Philadelphia: Review of 150 Consecutive Operations. PMID- 17862750 TI - IX. An Experimental Study of the Management of Post-Operative Thoracic Infections: A Preliminary Report. PMID- 17862752 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , held May 10, 1911: Stated Meeting. PMID- 17862753 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , held May 1, 1911: Stated Meeting. PMID- 17862754 TI - Splinting Skin Grafts and Granulating Surfaces. PMID- 17862755 TI - Open Treatment of Fractures. PMID- 17862756 TI - I. Acute Haematogenous Infection of the Kidney. PMID- 17862757 TI - II. Malignant Papillary Adenoma of the Kidney. PMID- 17862758 TI - III. Polyp of Urinary Bladder in a Thirteen Months Old Child: With a Review of the Literature. PMID- 17862759 TI - IV. Intraperitoneal Operation for Extensive Carcinoma of the Bladder, with New Method of Treating the Divided Ureter. PMID- 17862760 TI - V. Splenectomy for Rupture of Spleen: With Report of Four Cases. PMID- 17862761 TI - VI. Prolapsed Spleen with Acute Torsion; Splenopexy: With Table of Unreported Cases to Date. PMID- 17862762 TI - VII. Cysts of the Omentum. PMID- 17862763 TI - VIII. Linitis Plastica (Cirrhosis of Stomach): With a Report of a Case Cured by Gastro-Jejunostomy. PMID- 17862764 TI - IX. Extensive Removals of Intestine: Report of a Case of Recovery After Resection of Ten Feet Eight Inches of the Ileum. PMID- 17862765 TI - X. Right Inguinal Hernia following Appendectomy. PMID- 17862767 TI - XII. Muscle Grafting for Gunshot Wound of the Shoulder. PMID- 17862766 TI - XI. Fracture-Dislocation of the Atlas. PMID- 17862768 TI - XIII. On Impacted Fractures through and near the Femoral Neck. PMID- 17862769 TI - XIV. Note on Catgut Sterilization: A Preliminary Report. PMID- 17862770 TI - XV. The Treatment of Lacerated and Incised Wounds of the Extremities: With a Report of Five Typical Cases. PMID- 17862771 TI - XVI. Obesity and Its Surgical Treatment by Lipectomy. PMID- 17862772 TI - I. The Value of the Leucocyte Count in Acute Surgical Diseases. PMID- 17862773 TI - II. The Transplantation of Free Flaps of Fascia: An Experimental Study. PMID- 17862774 TI - III. Experiences in Thoracic Surgery under. Anaesthesia by the Intratracheal Insufflation of Air and Ether: With Remarks on the Value of the Method for General Anaesthesia. PMID- 17862775 TI - IV. Studies on Peritoneal Adhesions: With a Contribution to the Treatment of Denuded Bowel Surfaces. PMID- 17862776 TI - V. Considerations Relating to the Pathogenesis and Diagnosis of Surgical Diseases of the Pancreas. PMID- 17862777 TI - VI. Gastric and Duodenal Ulcer: A Record of 110 Recent Operations. PMID- 17862778 TI - VII. Early Diagnosis of Carcinoma of the Colon. PMID- 17862779 TI - VIII. Non-Traumatic Large Hemorrhage into the Kidney Substance or its Surroundings. PMID- 17862780 TI - IX. The Operative Treatment of the Deformity of Pott's Disease. PMID- 17862782 TI - XI. A New Container for Sterilized Operating Supplies. PMID- 17862781 TI - X. Modified Autogenous Grafting and Turning Skin Flaps to Cover Granulating Surfaces: Report of Extensive Burn Presenting Unusual Features. PMID- 17862784 TI - I. Surgical Aspects of Membranous Pericolitis. PMID- 17862783 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , held October 11, 1911: Stated Meeting. PMID- 17862785 TI - X. Fracture of the Sesamoid Bones. PMID- 17862786 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , held November 8, 1911: Stated Meeting. PMID- 17862787 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , held October 2, 1911: Stated Meeting. PMID- 17862788 TI - TRANSACTIONS OF THE GERMAN SURGICAL CONGRESS , held April 19-22, 1911: Fortieth Congress. PMID- 17862789 TI - II. The Surgical Treatment of Colitis. PMID- 17862790 TI - The International Society of Surgery. PMID- 17862791 TI - III. Surgical Treatment of Acute Pancreatitis. PMID- 17862792 TI - IV. The Incision for Lumbar Exposure of the Kidney. PMID- 17862793 TI - V. Epigastric Hernia, a Cause of Chronic Diarrhoea: With Report of a Case. PMID- 17862794 TI - VI. A Study of Sprain-Fracture. PMID- 17862795 TI - VII. A Dressing for Fracture of the Clavicle. PMID- 17862797 TI - IX. Clamp for Lining up Fractured Long Bones. PMID- 17862796 TI - VIII. Fracture of the Floor of the Acetabulum: With Four Illustrative Cases. PMID- 17862798 TI - PARATHYROIDS AND THEIR SURGICAL RELATION TO GOITRE. PMID- 17862800 TI - NOTES ON THE TECHNIC OF SUTURING BLOOD-VESSELS WITH A NEW INSTRUMENT. PMID- 17862799 TI - ARTERIOVENOUS ANASTOMOSIS-REVERSAL OF THE CIRCULATION-AS A PREVENTIVE OF GANGRENE OF THE EXTREMITIES: REVIEW OF THE LITERATURE AND REPORT OF SIX ADDITIONAL CASES. PMID- 17862801 TI - A NOTE ON THE DIVISION AND CIRCULAR SUTURE OF THE AORTA IN PREGNANT CATS. PMID- 17862803 TI - PROPHYLAXIS AND TREATMENT OF EPITHELIOMA OF THE LOWER LIP. PMID- 17862802 TI - OBSERVATIONS UPON A SERIES OF FORTY-THREE LAMINECTOMIES. PMID- 17862804 TI - ACUTE, SPONTANEOUS PERFORATION OF THE BILIARY SYSTEM INTO THE FREE PERITONEAL CAVITY: A REPORT OF SIX CASES FROM THE PRESBYTERIAN HOSPITAL OF NEW YORK AND 108 CASES FROM THE LITERATURE. PMID- 17862806 TI - NOTE ON THE MESOTHELIOMATA (SO-CALLED HYPERNEPHROMATA) OF THE KIDNEY. PMID- 17862805 TI - THE ERROR OF OVERLOOKING URETERAL OR RENAL STONE UNDER THE DIAGNOSIS OF APPENDICITIS. PMID- 17862807 TI - THE SURGICAL TREATMENT OF DIVERTICULA OF THE URINARY BLADDER: WITH THE REPORT OF A CASE AND A NEW DEVICE FOR FACILITATING THE OPERATION. PMID- 17862808 TI - PRIMARY TUBERCULOSIS OF THE PENIS: I. A REPORT OF TWO CASES OF PRIMARY TUBERCULOSIS OF THE PENIS FOLLOWING NON-RITUAL CIRCUMCISION. PMID- 17862809 TI - PRIMARY TUBERCULOSIS OF THE PENIS: II. NOTE ON PRIMARY TUBERCULOSIS OF THE FORESKIN. PMID- 17862811 TI - INDICATIONS FOR AND AGAINST THE OPERATIVE TREATMENT OF SIMPLE FRACTURES. PMID- 17862810 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, Held at the German Hospital, New York, October 25, 1911. PMID- 17862812 TI - THE TREATMENT OF SIMPLE FRACTURES: A STUDY OF SOME END RESULTS. PMID- 17862814 TI - OSTEOMYELITIS OF THE LONG BONES: A STUDY OF NINETY-FOUR CASES FROM THE CHILDREN'S HOSPITAL, BOSTON. PMID- 17862813 TI - LUXATION OF THE ULNA FORWARD AT THE WRIST (WITHOUT FRACTURE): WITH REPORT OF A CASE. PMID- 17862815 TI - THE DIAGNOSIS OF DIAPHRAGMATIC HERNIA. PMID- 17862816 TI - MANAGEMENT OF THE OPENING IN THE TRANSVERSE MESOCOLON IN COMPLETING THE OPERATION FOR POSTERIOR GASTROJEJUNOSTOMY. PMID- 17862817 TI - SARCOMA OF THE SMALL INTESTINE. PMID- 17862818 TI - INVERSION OF MECKEL'S DIVERTICULUM: WITH A REPORT OF SIX CASES. PMID- 17862819 TI - PRIMARY SARCOMA OF THE MALE URETHRA: REPORT OF A CASE. PMID- 17862820 TI - A COMBINATION ABDOMINAL RETRACTOR. PMID- 17862821 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting held December 4, 1911. PMID- 17862822 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, Held at the Presbyterian Hospital, November 22, 1911. PMID- 17862823 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, held December 13, 1911. PMID- 17862824 TI - CEPHALIC TETANUS: WITH REPORT OF A CASE. PMID- 17862825 TI - TREATMENT OF HEART WOUNDS: REPORT OF SUCCESSFUL CARDIORRHAPHY AND TABULATION OF CASES. PMID- 17862826 TI - PNEUMECTOMY: ITS POSSIBILITIES: REPORT OF A CASE OF PARTIAL LUNG EXCISION. PMID- 17862827 TI - TUMORS OF THE MALE BREAST. PMID- 17862828 TI - THE CLINICAL FEATURES AND TREATMENT OF ACUTE PERFORATING GASTRIC AND DUODENAL ULCER. PMID- 17862829 TI - THE REPAIR OF HERNIAE FROM THE PERITONEAL SIDE OF THE ABDOMINAL WALL. PMID- 17862830 TI - CONGENITAL MALFORMATIONS OF THE URETERS. PMID- 17862831 TI - OPERATION FOR ANEURISMAL VARIX OF THE POPLITEAL VESSELS. PMID- 17862833 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, held at the New York Hospital, January 24, 1912. PMID- 17862832 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, held at the Mt. Sinai Hospital, January 10, 1912. PMID- 17862834 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, held January 8, 1912. PMID- 17862835 TI - ESTIMATION OF VITAL RESISTANCE OF PATIENT WITH REFERENCE TO POSSIBILITY OF RECOVERY. PMID- 17862836 TI - THE WIRING OF OTHERWISE INOPERABLE ANEURISMS: WITH REPORT OF CASES. PMID- 17862837 TI - A FURTHER CONSIDERATION OF AN OPERATION FOR POTT'S DISEASE OF THE SPINE: WITH REPORT OF CASES FROM THE SERVICE OF THE NEW YORK ORTHOPAEDIC HOSPITAL. PMID- 17862838 TI - THE CLINICAL FEATURES AND TREATMENT OF ACUTE PERFORATING GASTRIC AND DUODENAL ULCER. PMID- 17862839 TI - INTESTINAL OBSTRUCTION DUE TO GALL-STONES: WITH REPORT OF THREE SUCCESSFUL CASES. PMID- 17862841 TI - "LE RHUMATISME TUBERCULEUX" (PONCET). PMID- 17862840 TI - A NEW DECOMPRESSION OPERATION FOR THE BRAIN. PMID- 17862842 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, held February 14, 1912. PMID- 17862843 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, held February 5, 1912. PMID- 17862844 TI - GENERAL INFECTION FOLLOWING ACUTE TONSILLITIS. PMID- 17862845 TI - A THORACIC ANEURISM TREATED WITH GOLD WIRE AND GALVANISM: WITH NOTES ON A PREVIOUS CASE AND ON EXPERIMENTAL STUDIES. PMID- 17862846 TI - ADHESIONS OF THE UPPER ABDOMEN. PMID- 17862847 TI - INVOLVEMENT OF REGIONAL LYMPHATIC GLANDS IN CARCINOMA OF THE STOMACH: FROM A STUDY OF 200 RESECTED SPECIMENS. PMID- 17862848 TI - CONGENITAL ABSENCE OF CAECUM AND ASCENDING COLON. PMID- 17862849 TI - PREVASCULAR FEMORAL HERNIA. PMID- 17862850 TI - OBSERVATIONS ON THE RADICAL CURE OF HERNIA. PMID- 17862851 TI - THE VALUE OF ARTERIOVENOUS ANASTOMOSIS IN GANGRENE OF THE LOWER LIMB. PMID- 17862852 TI - FRACTURE OF THE RADIUS ABOVE THE ATTACHMENT OF THE PRONATOR QUADRATUS MUSCLE. PMID- 17862853 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, held at Bellevue Hospital, February 28, 1912. PMID- 17862854 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. Stated Meeting, held March 13, 1912. PMID- 17862855 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. Stated Meeting, held March 4, 1912. PMID- 17862856 TI - GAUZE LOST IN A BONE CAVITY FOR FIFTEEN MONTHS. PMID- 17862857 TI - CHRONIC OXYURIS INFECTION WITHOUT APPENDICEAL SYMPTOMS CURED BY APPENDECTOMY. PMID- 17862858 TI - I. Nephrectomy: A Study Based on the Records of 112 Cases. PMID- 17862859 TI - VII. On Drainage after Intrathoracic Operations with Special Reference to the OEsophagus. PMID- 17862861 TI - IX. Acute Diverticulitis of the Sigmoid Flexure of the Colon. PMID- 17862860 TI - VIII. Acute Pancreatitis with Very Extensive Fat Necrosis. PMID- 17862862 TI - X. Hemorrhage into the Peritoneal Cavity Caused by Accidental Rupture of the Ovary. PMID- 17862864 TI - XII. The Tomato Joint. PMID- 17862863 TI - XI. Tuberculosis of the Bladder, Ureter, and Kidney: Report of Cases. PMID- 17862865 TI - XIII. Acute Inflammation of Long Bones. PMID- 17862867 TI - XV. End Results of Fracture of the Shaft of the Femur. PMID- 17862866 TI - XIV. Surgery of the Long Bones. PMID- 17862868 TI - XVI. Safety in the Operative Fixation of Infected Fractures of Long Bones. PMID- 17862869 TI - XVII. Intratracheal Insufflation Anaesthesia (Meltzer-Auer): Observations on a Series of 216 Anaesthesias with the Elsberg Apparatus. PMID- 17862870 TI - II. The End Results in Sixty-three Cases of Operation for Brain Tumor. PMID- 17862871 TI - III. Bullet Wound of the Spinal Cord between the First and Second Dorsal Vertebrae; Laminectomy; Removal of the Bullet; Complete Recovery. PMID- 17862872 TI - IV. The Treatment of the Defect Occasioned by Partial Excision of the Inferior Maxilla. PMID- 17862873 TI - V. Surgery of the Thymus Gland. PMID- 17862874 TI - VI. The Treatment of Subclavian Aneurism. PMID- 17862875 TI - I. The Value of Direct Gastroduodenoscopy in Affections of the Stomach and the Duodenum. PMID- 17862876 TI - II. The Conservative Treatment of Giant-Cell Sarcoma, with the Study of Bone Transplantation. PMID- 17862878 TI - IV. Nephrectomy (Concluded): A Study Based on the Records of 112 Cases. PMID- 17862877 TI - III. The Radical Operation for the Relief of Cancer of the Rectum and Rectosigmoid. PMID- 17862879 TI - V. Observations on the Diagnosis of Renal Tuberculosis, the Indications for Nephrectomy in its Treatment and the Technic of the Operation. PMID- 17862880 TI - VI. Acute Haematogenous Infection of One Kidney in a Person Apparently Well. PMID- 17862881 TI - VII. Acute Unilateral Infection of the Kidney. PMID- 17862882 TI - VIII. Adherent Hernias of the Large Intestine. PMID- 17862883 TI - IX. An Apparatus for Intratracheal Insufflation. PMID- 17862884 TI - X. Picric Acid as a Skin Disinfectant. PMID- 17862885 TI - TRANSACTIONS OF THE AMERICAN SURGICAL ASSOCIATION , held at Montreal, Canada, May 29, 30, 31, 1912: Annual Meeting. PMID- 17862886 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , held March 27, 1912: Stated Meeting. PMID- 17862887 TI - I. A Discussion of Bone Transplantation and the Use of a Rib as a Graft. PMID- 17862889 TI - III. Bilateral Congenital Fistulae of the Lower Lip. PMID- 17862888 TI - II. An Unusual Sinus Frontalis. PMID- 17862890 TI - IV. Note on Intrathoracic Surgery: Division and Circular Suture of the Thoracic Aorta. PMID- 17862891 TI - V. Note on the Transplantation of Fresh Venous Segments. PMID- 17862892 TI - VI. The Results of Ligation of One Ureter. PMID- 17862893 TI - VII. On Appendix Tumor. PMID- 17862894 TI - VIII. Foreign Body Appendicitis: With Especial Reference to the Domestic Pin; an Analysis of Sixty-Three Cases. PMID- 17862895 TI - IX. The Relation of the Ileocaecal Folds to Appendectomy. PMID- 17862897 TI - XI. Separation of the Epiphysis of the First Metacarpal Bone: With Report of a Case. PMID- 17862896 TI - X. Fractures of the Greater Tuberosity of the Humerus: With an Operative Procedure for Fixation. PMID- 17862898 TI - XII. An Operating Room Mirror: A Device to Facilitate the View of Operations in the Operating Theatre. PMID- 17862900 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , held April 24, 1912: Stated Meeting. PMID- 17862899 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , held April 10, 1912: Stated Meeting. PMID- 17862902 TI - Biliary Calculi of Large Size Removed from Common Duct. PMID- 17862901 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , held April 1, 1912: Stated Meeting. PMID- 17862903 TI - A Note on the Mistake of Adopting the Inclined or Fowler Position after the Operation of Gastrojejunostomy. PMID- 17862904 TI - I. Tuberculosis of the Kidney. PMID- 17862905 TI - II. A Consideration of Gas Bacillus Infection with Special Reference to Treatment: A Resume of the Literature and a Report of Twenty-Five New Cases. PMID- 17862906 TI - III. Mediastinal and Pericardial Infections in Relation to Emergency Abdominal Surgery. PMID- 17862908 TI - V. Acute Phlegmonous Inflammation of the Large Intestine. PMID- 17862907 TI - IV. Trans-Duodenal Choledochotomy for Stone in the Ampulla of Vater: With Fistulous Communication Between the Gall-Bladder and the Duodenum. PMID- 17862909 TI - VI. The Recognition and Treatment of Lesions of the Right Iliac Fossa other than Appendicitis. PMID- 17862910 TI - VII. A Study of Sprain-Fracture as an Essential to the Occurrence of Dislocation. PMID- 17862911 TI - VIII. The Treatment of Intracapsular Fractures of the Hip. PMID- 17862912 TI - IX. Treatment of Dislocation of the Head of the Radius Complicated by Fracture of the Ulna. PMID- 17862914 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , held May 6, 1912: Stated Meeting. PMID- 17862913 TI - X. On the Freeing of Fragments Preliminary to the Operative Reduction of Fracture of the Femur. PMID- 17862915 TI - I. Tetany Following Extirpation of the Thyroid: With Report of a Case. PMID- 17862916 TI - II. The Surgical Treatment of Aortic Aneurism: Report on a Case Successfully Treated by Production of White Thrombus. PMID- 17862917 TI - III. Primary Sarcoma of the Peritoneum: Report of a Case. PMID- 17862919 TI - V. Malignant Tumors of the Mesentery: With Report of a Case. PMID- 17862918 TI - IV. Thrombosis of the Mesenteric Vessels. PMID- 17862920 TI - VI. Volvulus of the Stomach. PMID- 17862922 TI - VIII. The Clinical Diagnosis of Congenital Anomaly in the Kidney and Ureter. PMID- 17862921 TI - VII. Tumors of the Ampulla of Vater: With a Report of Two Cases. PMID- 17862924 TI - X. The Treatment of Fistula in Ano: With Especial Reference to the Whitehead Operation. PMID- 17862923 TI - IX. The Operative Procedure in Cancer of the Prostate. PMID- 17862925 TI - XI. Salvarsan and Neo-Salvarsan; Their Intravenous Injection. PMID- 17862926 TI - XII. Ivory Dowel for Preserving the Finger in a Case of Enchondroma of a Phalanx Complicated by Fracture. PMID- 17862927 TI - XIII. The Reduction of the Fragments in Fractures of the Long Bones: Two Methods Available Previous to Plating. PMID- 17862928 TI - XIV. Tying the Knots of Ligatures and Sutures with One Hand. PMID- 17862930 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , held May 8, 1912: Stated Meeting. PMID- 17862929 TI - XV. A Modification of Bartlett's Gastro-enterostomy Clamp. PMID- 17862932 TI - II. Acute Unilateral Haematogenous Infections of the Kidney. PMID- 17862931 TI - I. Fatal Post-Operative Embolism. PMID- 17862933 TI - III. The Management of the Grave Emergency Cases of Extra-Uterine Pregnancy: With a Study of 137 Cases of Tubal and Interstitial Pregnancy at the Massachusetts General Hospital from 1902 to 1910. PMID- 17862934 TI - IV. Operative Treatment of Fractures. PMID- 17862935 TI - V. Contribution to the Etiology of Congenital Dislocation of the Hip. PMID- 17862936 TI - VI. Bone Plating in Irreducible Fracture of the Clavicle. PMID- 17862937 TI - VII. Traumatic Separation of the Lower Epiphysis of the Femur. PMID- 17862938 TI - VIII. Observations on Fracture of the Odontoid Process of the Axis with Intermittent Pressure Paralysis. PMID- 17862939 TI - IX. Mediotarsal Subluxation as Shown by the X-Ray. PMID- 17862941 TI - XI. Displacements of the Colon. PMID- 17862940 TI - X. Multiple Gunshot Wounds of Intestine Without Perforation of Lumen. PMID- 17862942 TI - XII. Gangrene of Ileum Complicating Appendicitis. PMID- 17862943 TI - XIII. Appendicitis in an Infant Sixteen Days Old with Appendix in an Inguinal Hernial Sac. PMID- 17862944 TI - XIV. Primary Sarcoma of the Spleen. PMID- 17862945 TI - XV. Bevan's Operation for Undescended Testicle: With a Suggestion as to One Factor Causing Undescended Testicle. PMID- 17862946 TI - XVI. Traumatic Femoral Aneurism Cured by Matas's Method of Endo-Aneurismorrhaphy. PMID- 17862947 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , held October 9, 1912: Stated Meeting. PMID- 17862948 TI - I. Gastrocoloptosis: Its Pathological Signification and its Surgical Treatment. PMID- 17862949 TI - X. An Instrument for Establishing Fecal Drainage, with a Report of Its Use on a Case, and a Consideration of the Site for Making a Fecal Fistula in Low-Seated Intestinal Obstruction. PMID- 17862950 TI - XI. Rupture or Sprain Fracture of the Ligamentum Patellae. PMID- 17862952 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , held October 23, 1912: Stated Meeting. PMID- 17862951 TI - XII. A Method of Focusing Several Electric Lights on the Field of Operation. PMID- 17862954 TI - Operation Upon a New-born Babe. PMID- 17862953 TI - Acute Suppurating Bursitis of the Subdeltoid Bursa. PMID- 17862955 TI - II. A New Principle in OEsophagoscopy and Gastroscopy. PMID- 17862956 TI - III. Intratracheal Insufflation Anaesthesia: Considered from its Physiological and Clinical Aspects. PMID- 17862957 TI - IV. The Anaesthetic Effects of the Intravenous Injection of Paraldehyde. PMID- 17862958 TI - V. Traumatic Rupture of the Spleen (Complete); Splenectomy. PMID- 17862959 TI - VI. Spontaneous Rupture of the Malarial Spleen: A Report of Three Cases. PMID- 17862960 TI - VII. The Use of a Murphy Button to Effect Duodenojejunostomy After Gastrojejunostomy. PMID- 17862961 TI - VIII. Ileus Due to Meckel's Diverticulum. PMID- 17862963 TI - I. An Approach to the Hypophysis through the Anterior Cranial Fossa. PMID- 17862962 TI - IX. Extrasaccular Hernia. PMID- 17862964 TI - II. Postoperative Thrombophlebitis. PMID- 17862966 TI - IV. Tuberculosis of the Breast. PMID- 17862965 TI - III. Mutiple Myelomata, with Numerous Spontaneous Fractures and Albumosuria. PMID- 17862968 TI - VI. Strangulated Inguinal Hernia in Early Infancy. PMID- 17862967 TI - V. Angulation of the Junction of the Hepatic and Common Ducts after Cholecystostomy, Simulating Common Duct Obstruction. PMID- 17862969 TI - VII. Hernia Adiposa: Fat Hernia, Fettbruch, Hernie Graisseuse. PMID- 17862971 TI - IX. The Reduction of Old Unreduced Dislocations of the Shoulders. PMID- 17862970 TI - VIII. Formation of an Artificial Vagina by Intestinal Transplantation. PMID- 17862972 TI - X. Chronic (Non-Suppurative) Hemorrhagic Osteomyelitis. PMID- 17862973 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , held November 13, 1912: Stated Meetings. PMID- 17862974 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , held November 27, 1912: Stated Meetings. PMID- 17862975 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , held October 7, 1912: Stated Meetings. PMID- 17862976 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , held November 4, 1912: Stated Meetings. PMID- 17862977 TI - I. Myositis Ossificans Traumatica: A Report of Three Cases Illustrating the Difficulties of Diagnosis from Sarcoma. PMID- 17862978 TI - II. Sub-temporal Muscle Drainage by the Aid of Silver Wire Drainage Mats in Cases of Congenital Hydrocephalus. PMID- 17862979 TI - III. The Thyrogenic Origin of Basedow's Disease. PMID- 17862981 TI - V. Temporary Arrest of the Heart Beats Following Incision of the Pericardium for Suppurative Pericarditis. PMID- 17862980 TI - IV. A Cheek Defect and Its Repair by Plastic Operation. PMID- 17862982 TI - VI. Membranous Pericolitis and Allied Conditions of the Ileocaecal Region. PMID- 17862983 TI - VII. Carcinoma of the Papilla of Vater. PMID- 17862984 TI - VIII. Tendon Fixation: A Preliminary Report of a Simple Operation for the Prevention of Deformity in Paralytic Talipes. PMID- 17862985 TI - IX. The End Result of Excision of the Elbow for Tuberculosis. PMID- 17862986 TI - X. The Arrest of Hemorrhage from Bone by Plugging with Soft Tissues. PMID- 17862987 TI - XI. An Operating Table for Use in Animal Research. PMID- 17862988 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , held December 11, 1912: Stated Meeting. PMID- 17862989 TI - I. Congenital Internal Hydrocephalus: Its Treatment by Drainage of the Cisterna Magna into the Cranial Sinuses. PMID- 17862990 TI - II. The Effect of the Removal of the Hypophysis in the Dog. PMID- 17862991 TI - III. Consecutive Displacement of the Cerebral Hemisphere in the Localization and Removal of Intracerebral Tumors and Hemorrhages (Apoplectic Hemorrhages and Clots): With a Description of the Operative Technic. PMID- 17862992 TI - IV. Coexisting Infection and Sarcoma of the Thyroid. PMID- 17862993 TI - V. Experimental Devascularization of Intestine with and without Mechanical Obstruction. PMID- 17862995 TI - VII. The Embryogenetic Relationships of Tumors of the Kidney, Suprarenal, and Testicle. PMID- 17862994 TI - VI. The Surgery of the Single and Horseshoe Kidney. PMID- 17862996 TI - VIII. Excision and Suture in the Treatment of Dense, Close, Urethral Strictures. PMID- 17862997 TI - IX. Operative Fixation as a Cause of Delay in Union of Fractures. PMID- 17862998 TI - X. Treatment of Volkmann's Contracture: A Report of Two Cases with Description of Apparatus. PMID- 17862999 TI - XI. Infections of the Hand: A Review of 90 Cases. PMID- 17863000 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , held December 2, 1912: Stated Meeting. PMID- 17863001 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , held January 8, 1913: Stated Meeting. PMID- 17863002 TI - An Artificial Hand of the Middle Ages. PMID- 17863003 TI - I. Arthroplasty. PMID- 17863004 TI - II. The Identity of Cause of Aseptic Wound Fever and So-called Post-Operative Hyperthyroidism and Their Prevention. PMID- 17863006 TI - IV. Cysts of the Spleen: A Pathological and Surgical Study. PMID- 17863005 TI - III. The Surgical Significance of the Accessory Pancreas. PMID- 17863007 TI - V. Pathologic Data Obtained from Ulcers Excised from the Anterior Wall of the Duodenum. PMID- 17863008 TI - VI. Remarks on Fatal Hemorrhage from Erosion of the Gastroduodenal Artery by Duodenal Ulcers. PMID- 17863009 TI - VII. Acute Perforated Duodenal and Gastric Ulcers: Report of 25 Cases Occurring at the German Hospital in the Last Six Years. PMID- 17863010 TI - VIII. Resection of One-third of the Colon for Irreducible Intussusception in an Infant Five Days Old. PMID- 17863011 TI - IX. Complications Following Surgical Operations: A Report of the Complications and Deaths in a Series of 5835 Surgical Operations Performed in the Mayo Clinic, St. Mary's Hospital, in the Year 1912. PMID- 17863012 TI - X. Abolishing Pain after Operations With Nerve Block a Distance. PMID- 17863013 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , held January 6, 1913: Stated Meeting. PMID- 17863014 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , held January 22, 1913: Stated Meeting. PMID- 17863015 TI - The Glasgow Lister Ward and Museum. PMID- 17863016 TI - I. Lymphangioplasty: Handley's Method. PMID- 17863017 TI - II. Interscapulothoracic Amputation of the Shoulder. PMID- 17863018 TI - III. Solitary Cysts of the Liver. PMID- 17863019 TI - IV. Gas Cysts of the Intestine: Pneumatosis Cystoides Intestinorum Hominis. PMID- 17863020 TI - V. The Etiology of Kidney Cysts: Illustrated by a Cyst Due to Obstructive Calcareous Papillitis. PMID- 17863021 TI - VI. An Experimental Study of Several Methods of Suturing the Kidney. PMID- 17863022 TI - VII. "Dumb-Bell" Kidney. PMID- 17863023 TI - VIII. Traumatic Hydronephrosis: With Report of a Case. PMID- 17863024 TI - IX. The Cause of Pain in Pyelography with Report of Accident and Experimental Findings. PMID- 17863025 TI - X. Primary Tuberculosis of the Glans Penis. PMID- 17863026 TI - XI. On the Formation of Bone in the Human Penis. PMID- 17863028 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , held February 3, 1913: Stated Meeting. PMID- 17863027 TI - XII. Anterior Gastro-Enterostomy: Report of a Case of Diverticula of the Jejunum. PMID- 17863029 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , held February 12, 1913: Stated Meeting. PMID- 17863030 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , held February 26, 1913: Stated Meeting. PMID- 17863031 TI - I. The American Surgical Association. Its Influence on the Growth and Development of American Surgery. PMID- 17863033 TI - X. A Note on Cancer of the Thyroid, and Its Extension to the Lungs by Means of the Blood-vessels. PMID- 17863032 TI - II. Fibromatosis of the Stomach and Its Relationships to Ulcer and to Cancer. PMID- 17863034 TI - XI. Hygroma Cysticum Colli: Its Structure and Etiology. PMID- 17863036 TI - III. Diagnosis and Treatment of Fractures Involving the Knee-joint: Including Epiphyseal Separation. PMID- 17863035 TI - XII. Exclusion of the Bladder, an Operation of Necessity and Expediency. PMID- 17863037 TI - IV. An Analysis and Study of 724 Major Amputations. PMID- 17863038 TI - V. Snapping Hip (Hanche a Ressort; Schnellende Hufte). PMID- 17863039 TI - VI. Five Cases of Suture of the Heart. PMID- 17863040 TI - VII. Aneurismorrhaphy: Two Cases of Aneurism Treated by Matas' Methods. PMID- 17863041 TI - VIII. Arteriovenous Anastomosis for Threatened Gangrene of the Foot. PMID- 17863042 TI - IX. Contribution to the Study of Sarcoma of the Femur: Periosteal Round-Celled Sarcoma of the Femur, Involving Two-Thirds of the Shaft, with Very Extensive Multiple Metastases-Apparent Cure by the Mixed Toxins of Erysipelas and Bacillus Prodigiosus. Well 10(1/2) Years, when a Malignant Tumor (Sarcoma and Epithelioma) Developed in the Thigh at the Site of an Old X-Ray Dermatitis. PMID- 17863043 TI - I. The Surgery of the Pancreas: I. Injuries to the Pancreas in the Course of Operations on the Stomach. II. Injuries to the Pancreas in the Course of Operations on the Spleen. III. Resection of Half the Pancreas for Tumor. PMID- 17863044 TI - II. Pancreatic and Peripancreatic Lymphangitis. PMID- 17863045 TI - III. Laryngectomy for Cancer. PMID- 17863047 TI - V. Partial Occlusion of the Thoracic and Abdominal Aortas by Bands of Fresh Aorta and of Fascia Lata. PMID- 17863046 TI - IV. (I) The Excision of Both Lobes of the Thyroid Gland for the Cure of Graves's Disease. (II) The Preliminary Ligation of the Thyroid Arteries and of the Inferior in Preference to the Superior Artery. PMID- 17863048 TI - VI. The Surgery of the Pulmonary Artery. PMID- 17863049 TI - VII. Sarcoma of the Chest Wall. PMID- 17863050 TI - VIII. Acute Perforating Sigmoiditis in Children. PMID- 17863051 TI - IX. On Excision of the Infarct in Acute Haematogenous Infections of the Kidney. PMID- 17863052 TI - X. The Technic of Nephro-, Pyelo-, and Ureterolithotomy. PMID- 17863053 TI - XI. Rupture of the Bladder: With Report of Three Unusual Cases. PMID- 17863055 TI - XIII. The Surgical Aspects of Purpura. PMID- 17863054 TI - XII. Sarcoma of the Stomach. PMID- 17863056 TI - XIV. Aneurism of the Internal Iliac: Probably Immediately Following a Severe Instrumental Delivery: Operation and Partial Cure. PMID- 17863057 TI - TRANSACTIONS OF THE AMERICAN SURGICAL ASSOCIATION. Meeting, held in Washington, D. C., May 6, 7 and 8, 1913. PMID- 17863058 TI - I. OEsophagoplasty. PMID- 17863059 TI - II. Some Surgical Features of Injuries of the Spine, with Special Reference to Spinal Fracture. PMID- 17863061 TI - IV. Some Anatomic and Physiologic Principles Concerning Pyloric Ulcer. PMID- 17863060 TI - III. Conclusions Drawn from an Experimental Investigation into the Practicability of Reducing the Calibre of the Thoracic Aorta by a Method of Plication or Infolding of its Walls, by Means of a Lateral Parietal Suture Applied in One or More Stages. PMID- 17863062 TI - V. The Relationship Between Gastric and Pancreatic Carcinoma. PMID- 17863063 TI - VI. Subdiaphragmatic Abscess. PMID- 17863064 TI - VII. Experimental Anatomic and Physiologic Observations Bearing Upon the Total Extirpation of the Colon. PMID- 17863066 TI - IX. The Hernial Sac in Its Relation to Concealed Intestinal Injuries. PMID- 17863065 TI - VIII. Diverticulitis of the Sigmoid. PMID- 17863067 TI - X. On the Development of Malignant Disease of the Cervical Stump After Supravaginal Hysterectomy. PMID- 17863069 TI - XII. Purpura of the Bladder: Report of a Case with a Description of the Cystoscopic Appearances. PMID- 17863068 TI - XI. Sacrococcygeal Tumors: With a Report of a Large Teratoma. PMID- 17863070 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , held March 12, 1913: Stated Meeting. PMID- 17863071 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , held March 26, 1913: Stated Meeting. PMID- 17863072 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , held March 3, 1913: Stated Meeting. PMID- 17863074 TI - II. Excessive Thickening of Thiersch Grafts Caused by a Component of Scarlet Red (Amidoazotoluol). PMID- 17863073 TI - I. The Treatment of Tuberculous Cervical Lymphadenitis. PMID- 17863075 TI - III. Embolism and Thrombosis of the Superior Mesenteric Artery: A Report of One Case. PMID- 17863076 TI - IV. The Cause and Treatment of Certain Unfavorable After-effects of Gastro enterostomy. PMID- 17863077 TI - V. Rectus Transplantation for Deficiency of Internal Oblique Muscle, in Certain Cases of Inguinal Hernia. PMID- 17863078 TI - VI. Recurrence of Inguinal Hernia. PMID- 17863079 TI - VII. Contracture of the Psoas Parvus Muscle Simulating Appendicitis. PMID- 17863080 TI - VIII. The Reduction of the Fragments Preliminary to Internal Splintage in Cases of Fracture of the Long Bones. PMID- 17863081 TI - IX. Fractures Through the Trochanters of the Femur. PMID- 17863083 TI - XI. Uncomplicated Fractures of the Tarsal Scaphoid. PMID- 17863082 TI - X. Simultaneous Fracture of Both Patellae: With Report of Two Cases and a Review of the Literature. PMID- 17863084 TI - XII. Cyst of the Fifth Metacarpal Bone: A Complication of Chronic Osteo Arthritis. PMID- 17863085 TI - XIII. Direct Suture of the Brachial Artery Following Rupture, Result of Traumatism. PMID- 17863086 TI - XIV. Suction Tip for Aspiration in Abdominal Operations. PMID- 17863087 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , held April 7, 1913: Stated Meeting. PMID- 17863088 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , held April 9, 1913: Stated Meeting. PMID- 17863089 TI - I. Traumatic Erb's Paralysis in the Adult. PMID- 17863090 TI - II. Splenic Anaemia, with Special Reference to Etiology and Surgical Treatment. PMID- 17863091 TI - III. Exactness in Diagnosis and Conservatism in Treatment of Renal Calculus. PMID- 17863092 TI - IV. Transperitoneal Resection of a Diverticulum of the Bladder. PMID- 17863093 TI - V. Report of 105 Cases of Strangulated Hernia. PMID- 17863094 TI - VI. Immediate and Late Results of the Whitehead Operation for Hemorrhoids: A Review of 470 Cases. PMID- 17863096 TI - VIII. A Further Note on Reduction of Fragments in Fractures of the Long Bones at Open Operation. PMID- 17863095 TI - VII. A Method for the Mechanical Fixation of Transverse Fractures. PMID- 17863097 TI - IX. A Development of the Author's Gastro-enterostomy Clamp. PMID- 17863099 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , held April 23, 1913: Stated Meeting. PMID- 17863098 TI - X. The Chevalier Jackson Method of Finger Elevation of the Hyoid Bone in General Anaesthesia. PMID- 17863100 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , held May 14, 1913: Stated Meeting. PMID- 17863101 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , held May 5, 1913: Stated Meeting. PMID- 17863102 TI - Later History of Case in which Ten Feet Eight Inches of Gut Were Removed. PMID- 17863103 TI - I. Studies in Blood-pressure Before, During, and After Operations with Reference to the Early Recognition, Prevention, and Treatment of Shock. PMID- 17863104 TI - II. Tumors of the Carotid Body. PMID- 17863105 TI - III. The Early Diagnosis of Hydronephrosis by Pyelography and Other Means. PMID- 17863107 TI - V. Report of a Case of Pelvic Kidney: Diagnosis Before Operation. PMID- 17863106 TI - IV. The Value and Limitation of Diastase, Urea, and Phthalein in Estimating Renal Function in Association with Ureteral Catheterization. PMID- 17863108 TI - VI. Myoma of the Stomach. PMID- 17863109 TI - VII. Primary Sarcoma of the Large Intestine. PMID- 17863110 TI - VIII. Non-rotation of the Intestine: Its Relation to High, Retrocaecal and Aberrant Positions of the Appendix. PMID- 17863112 TI - X. The Anatomy of a Case of Carcinoma Recti. PMID- 17863111 TI - IX. A Retrorectus Laparotomy Incision and Closure. PMID- 17863113 TI - XI. Strangulation of the Undescended Testis. PMID- 17863115 TI - Contracture of Psoas Muscle Simulating Appendicitis. PMID- 17863114 TI - XII. Sarcoma of the Chest Wall. PMID- 17863116 TI - The American Association of Anaesthetists. PMID- 17863117 TI - Accuracy in Anaesthesia: Advantage, Technic and Dosage in Automatic Insufflation of Vapors and Gases. Preliminary Tables and Charts of Ether Anaesthesia. PMID- 17863118 TI - Reflex Action During General Surgical Anaesthesia. PMID- 17863119 TI - Intravenous Anaesthesia. PMID- 17863120 TI - Nitrous Oxide and Oxygen Narcosis. PMID- 17863121 TI - Intratracheal Anaesthesia: A. By Nitrous Oxide and Oxygen. B. By Nitrous Oxide and Oxygen Under Conditions of Differential Pressure. PMID- 17863122 TI - Deaths from Anaesthesia: And Lessons to be Drawn from them. PMID- 17863124 TI - Stovaine Spinal Analgesia in Prison Surgery. PMID- 17863123 TI - The Question of Anaesthesia in Goitre Operations. PMID- 17863125 TI - Medicolegal Aspects of Anaesthesia. PMID- 17863126 TI - I. A Further Contribution to the Study of Pericolic Membranous Films and Bands. PMID- 17863127 TI - VII. The Use of Citrate Solutions in the Prevention of Peritoneal Adhesions. PMID- 17863128 TI - VIII. Incidence of Gall-stones and Other Calculi Among Laborers in the Panama Canal Zone. PMID- 17863130 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , held October 8, 1913: Stated Meeting. PMID- 17863129 TI - IX. Interscapulothoracic Amputation of the Shoulder With Complete Excision of the Clavicle: A Report of Three Cases. PMID- 17863131 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , held October 6, 1913: Stated Meeting. PMID- 17863132 TI - II. Pericolic Membranes and Lane's Kink: With Report of Nine Cases. PMID- 17863134 TI - IV. Cancer and Precancerous Conditions. PMID- 17863133 TI - III. Pericolitis Sinistra. PMID- 17863136 TI - VI. Pneumococcic Arthritis. PMID- 17863135 TI - V. The Localization of Foreign Bodies Within the Tissues with a Description of a Method of Localization. PMID- 17863137 TI - I. The Present Status of Bismuth Paste Treatment of Suppurative Sinuses and Empyema. PMID- 17863138 TI - II. The Nature of Shock: Its Relation to Acapnia and to Changes in the Circulation of the Blood and to Exhaustion of the Nerve Centres. PMID- 17863139 TI - III. The Dietetic Treatment of Gangrene in Diabetes Mellitus. PMID- 17863140 TI - IV. Complete Avulsion of the Scalp: With a Report of a Case. PMID- 17863141 TI - V. Intrathoracic Goitre: Report of Two Cases with Marked Displacement of Trachea. PMID- 17863142 TI - VI. An OEsophagoscope with Direct Outside Illumination. PMID- 17863145 TI - IX. Stenosis of the Pylorus in Infancy. PMID- 17863146 TI - X. Intussusception: Review of Twenty-Seven Cases. PMID- 17863143 TI - VII. The Relation of Posterior Subluxation of the Shoulder-joint to Obstetrical Palsy of the Upper Extremity. PMID- 17863144 TI - VIII. The Frequency and Significance of Injuries to the Acromion Process. PMID- 17863147 TI - XI. Modern Laboratory Methods in the Diagnosis of Surgical Diseases of the Genito urinary Tract. PMID- 17863149 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY , held November 3, 1913: Stated Meeting. PMID- 17863148 TI - XII. A Technic for Performing a Shockless Suprapubic Prostatectomy. PMID- 17863150 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY , held November 12, 1913: Stated Meeting. PMID- 17863151 TI - Thrombosis of the Mesenteric Vessels. PMID- 17863152 TI - I. Prostatism: The Surgical Anatomy and Pathology of the Operative Treatment. PMID- 17863154 TI - III. Prostatectomy in a General Surgical Practice: A Clinical Report. PMID- 17863153 TI - II. Suprapubic Versus Perineal Prostatectomy. PMID- 17863155 TI - IV. A Method of Exposing the Lower End of the Ureter. PMID- 17863156 TI - V. Rectovesical Echinococcus Cyst. PMID- 17863158 TI - VII. Post-operative Ileus. PMID- 17863157 TI - VI. Fracture of the Penis. PMID- 17863159 TI - VIII. Intestinal Obstruction Resulting from a Malignant Tumor of a Retained Testis Abdominis. PMID- 17863161 TI - X. Arthroplasty. PMID- 17863160 TI - IX. Obstructive Pelvic Lesions Associated with Chronic Diverticulitis. PMID- 17863162 TI - XI. Paralytic Toe-drop, Putti's Operation for Its Relief: With Report of a Case and Slight Modification of the Technic. PMID- 17863163 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , held December 1, 1913: Stated Meeting. PMID- 17863164 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , held November 26, 1913: Stated Meeting. PMID- 17863165 TI - I. The Methods Suggested for Bone Transplantations. PMID- 17863166 TI - II. Autogenous Bone Grafting for Fracture of the Patella. PMID- 17863167 TI - III. The Treatment of Ununited Fractures of the Tibia by the Transplantation of Bone. PMID- 17863168 TI - IV. The Treatment of Ununited Fractures of the Tibia by Bone Transplants: A Report of Five Transplantations with Firm Bony Union. PMID- 17863169 TI - V. Transvesical Prostatectomy in Two Stages. PMID- 17863171 TI - VII. Eversion of Bladder: As a Late Sequel of Mutilation Caused by Rape in Early Childhood. PMID- 17863170 TI - VI. The Normal Bladder and Its Sphincters and the Changes Following Suprapubic Prostatectomy. PMID- 17863173 TI - IX. Perforating Gastric and Duodenal Ulcers: With Report of Cases. PMID- 17863172 TI - VIII. Arteriovenous Aneurism of the External Iliac Vessels, with Wound of the External Iliac Vein. PMID- 17863174 TI - X. Peritoneal and Pleural Absorption, with Reference to Postural Treatment. PMID- 17863175 TI - XI. Subcutaneous Traumatic Rupture of the Normal Spleen. PMID- 17863176 TI - XII. Hernia of the Large Intestine: With Special Reference to "Sliding Hernia.". PMID- 17863178 TI - XIV. Simple and Complete Forms of Apparatus for Intratracheal Anaesthesia. PMID- 17863177 TI - XIII. Looping the Cardinal Ligaments in Uterine Prolapse. PMID- 17863179 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , held December 10, 1913: Stated Meeting. PMID- 17863180 TI - INTERNATIONAL SURGICAL ASSOCIATION: Fourth Congress, to be held April 13, 1914. PMID- 17863182 TI - II. Vaccine and Serum Therapy in Septicaemia: A Clinical Study of the Course and Treatment of III Cases. PMID- 17863181 TI - I. The Technic of Comparative Hyperaemia: Moszkowicz's Sign. PMID- 17863183 TI - III. The Advantages of the Double Resection in Certain Types of Goiter. PMID- 17863184 TI - IV. The Frequency of Carcinoma of the Appendix: A Report of 40 Cases (.44 per cent.) in 8039 Specimens. PMID- 17863185 TI - V. A Consideration of Certain Coexisting Lesions of the Gall-Bladder and Kidney. PMID- 17863186 TI - VI. Splenic Anaemia with Splenectomy (Banti's Disease): A Case Report, with Remarks. PMID- 17863187 TI - VII. Ileocaecal Tuberculosis. PMID- 17863188 TI - VIII. The Experimental Study of Intestinal Obstruction. PMID- 17863189 TI - IX. Sarcoma of the Small Intestine. PMID- 17863190 TI - X. The Surgical Treatment of Acute Gonorrhoeal Epididymitis by Epididymotomy. PMID- 17863191 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY. , held January 5, 1914: Stated Meeting. PMID- 17863192 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , held October 22, 1913: Stated Meeting. PMID- 17863193 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , held January 14, 1914: Stated Meeting. PMID- 17863194 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY. , held January 28, 1914: Stated Meeting. PMID- 17863195 TI - I. The Prophylaxis of Cancer. PMID- 17863196 TI - II. Systemic Blastomycosis. PMID- 17863197 TI - III. The Value of Gluzinski's Test in the Diagnosis of Gastric Ulcer. PMID- 17863198 TI - IV. A Method of Subtotal Gastrectomy. PMID- 17863199 TI - V. The Function of the Gastro-Enterostomy Opening in Cases of Permeable Pylorus. PMID- 17863200 TI - VI. Chronic Pancreatitis. PMID- 17863201 TI - VII. Suggestions Regarding the Anatomy of and the Surgical Technic in the Treatment of Jonnesco's Membrane. PMID- 17863202 TI - VIII. Bullet in the Pericardium: Auricular Fibrillation. PMID- 17863204 TI - X. Visceral Pleurectomy for Chronic Empyema. PMID- 17863205 TI - XI. The Pleural and Pulmonary Complications of Tropical Abscess of the Liver. PMID- 17863203 TI - IX. Pulmonary Abscess and Bronchiectasis: A Clinical Report. PMID- 17863206 TI - XII. The Causal Relation of Traumatism to Tuberculosis. PMID- 17863207 TI - XIII. Uncomplicated Tuberculous Foci in Bones and Their Treatment. PMID- 17863208 TI - XIV. Frontal Sinus Suppuration: The Establishment of Permanent Nasal Drainage; the Closure of External Fistulae; Epidermization of Sinus. PMID- 17863209 TI - XV. Blepharoplasty. PMID- 17863210 TI - XVI. Ligation of the Innominate Artery: With Report of a Successful Case. PMID- 17863211 TI - XVII. Distant Results of a Suture of the Heart Following a Wound by Pistol-Shot. PMID- 17863212 TI - XVIII. A Review of Ninety-nine Arthrotomies for Fracture of the Patella. PMID- 17863213 TI - EXPERIMENTAL OPERATIONS ON THE ORIFICES OF THE HEART. PMID- 17863214 TI - TRANSACTIONS OF THE AMERICAN SURGICAL ASSOCIATION. Annual Meeting Held in New York City, April 9, 10, and 11, 1914. PMID- 17863215 TI - THE SURGICAL ASPECTS OF BRONCHIECTASIS. PMID- 17863216 TI - THE CHOICE OF ANAESTHETIC IN OPERATING FOR ABSCESS OF THE LUNG: REPORT OF TWO CASES OPERATED UPON UNDER LOCAL ANAESTHESIA. PMID- 17863217 TI - RESULTS OF CONSERVATIVE TREATMENT OF CYSTIC DISEASE OF THE BREAST. PMID- 17863218 TI - THE TWO-STAGE OPERATION ESPECIALLY IN ITS RELATION TO TREATMENT OF CANCER. PMID- 17863219 TI - ARTERIOVENOUS ANASTOMOSIS OF THE FEMORAL VESSELS FOR IMPENDING GANGRENE. PMID- 17863220 TI - ON BRONCHIECTASIS. PMID- 17863221 TI - MELANOBLASTOMAS OF THE FOOT (CHROMATOPHOROMA, MELANOMA, MELANOSARCOMA). PMID- 17863222 TI - WAR SURGERY: THE PRESIDENT'S ADDRESS OPENING THE FOURTH CONGRESS OF THE INTERNATIONAL SOCIETY OF SURGERY. PMID- 17863223 TI - AMPUTATIONS. PMID- 17863224 TI - AMPUTATION OF THE HAND. PMID- 17863225 TI - AMPUTATIONS OF THE LEG. PMID- 17863226 TI - FREE TRANSPLANTATION. PMID- 17863227 TI - TISSUE AND ORGAN TRANSPLANTATION. PMID- 17863228 TI - CHRONIC ULCERS OF THE STOMACH AND DUODENUM. PMID- 17863229 TI - ULCER OF THE STOMACH AND OF THE DUODENUM. PMID- 17863231 TI - ACQUIRED DISEASE OF THE THYROID GLAND. PMID- 17863230 TI - THE DIAGNOSIS OF GASTRIC AND DUODENAL ULCER. PMID- 17863232 TI - HOW SHALL THE CLINICIAN INTERPRET WASSERMANN REACTION? PMID- 17863233 TI - SEMINAL VESICULITIS. PMID- 17863234 TI - THE TREATMENT OF BLADDER PAPILLOMA BY HIGH FREQUENCY DESTRUCTION. PMID- 17863235 TI - POLYPS OF THE MALE URETHRA. PMID- 17863236 TI - A METHOD OF TREATING ADHERENT PERFORATING ULCER OF THE POSTERIOR WALL AND LESSER CURVATURE OF THE STOMACH. PMID- 17863237 TI - CONGENITAL PYLORIC STENOSIS. PMID- 17863238 TI - LYMPHANGIO-ENDOTHELIOMATOUS GROWTHS OF THE PERITONEUM. PMID- 17863239 TI - TUMOR AT THE MEATUS URINARIUS IN THE FEMALE. PMID- 17863240 TI - TRAUMATIC INTRA-ACETABULAR SEPARATION OF THE PELVIC BONES. PMID- 17863241 TI - THE PREPARATION OF DRY BONY AREAS FOR SKIN GRAFTING. PMID- 17863242 TI - THUMB FORCEPS TO FACILITATE ANASTOMOSIS. PMID- 17863243 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 11 1914: Stated Meetings, Held February. PMID- 17863244 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 25, 1914: Stated Meetings, Held February. PMID- 17863245 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 2, 1914: Stated Meeting, Held February. PMID- 17863247 TI - PRIMARY SARCOMA OF THE LOWER END OF THE FEMUR INVOLVING THE SYNOVIAL MEMBRANE: WITH A CRITICAL REVIEW OF THE LITERATURE OF SYNOVIAL SARCOMA REPORT OF ONE CASE WITH COMPLETE PATHOLOGICAL AND RADIOGRAPHIC EXAMINATION. PMID- 17863246 TI - PRINCIPLES OF OPERATIVE TREATMENT OF THE DISEASES OF THE LARGE INTESTINE. PMID- 17863248 TI - A TREATMENT FOR OLD CONTRACTED CICATRICES. PMID- 17863249 TI - LAMINECTOMY FOR SPINAL TUMOR: A REPORT OF EXPERIENCES IN 37 CASES. PMID- 17863250 TI - ANEURISM OF THE SCIATIC ARTERY. PMID- 17863251 TI - DISAPPEARANCE OF RECURRENT MAMMARY CARCINOMA AFTER REMOVAL OF THE OVARIES. PMID- 17863253 TI - THE FREE TRANSPLANTATION OF FASCIA LATA: IN THE REPAIR OF VENTRAL AND INGUINAL HERNIAE WITH CASES. PMID- 17863252 TI - INJURIES OF THE GREAT TOE SESAMOIDS. PMID- 17863255 TI - FLASHLIGHT AUTOCHROM PHOTOGRAPHY OF PATHOLOGICAL SUBJECTS. PMID- 17863254 TI - A CRITICAL ANALYSIS OF THE TREATMENT OF FRACTURE OF THE NECK OF THE FEMUR. PMID- 17863256 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 11 1914: Stated Meetings, Held March. PMID- 17863257 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 25, 1914: Stated Meetings, Held March. PMID- 17863258 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 2, 1914: Stated Meeting, Held March. PMID- 17863259 TI - A Paramedian Coeliotomy Incision. PMID- 17863260 TI - The Red Stippling Sign of Gastric and Duodenal Ulcer. PMID- 17863261 TI - Treatment of Thoracic Aneurism with Potassium Iodide. PMID- 17863262 TI - An Evacuator for the Removal. During Operation, of Fluids from the Abdominal and other Cavities. PMID- 17863263 TI - SOME PROBLEMS IN THE EARLY DIAGNOSIS AND TREATMENT OF SARCOMA OF THE LONG BONES. PMID- 17863264 TI - EXPERIENCES IN THE TREATMENT OF MALIGNANT TUMORS BY RADIUM. PMID- 17863266 TI - A REVIEW OF 100 CONSECUTIVE OPERATIONS FOR GOITRE WITH ESPECIAL REFERENCE TO THE TREATMENT OF HYPERTHYROIDISM. PMID- 17863267 TI - CHRONIC CYSTIC MASTITIS. PMID- 17863265 TI - OSTITIS FIBROSA CYSTICA. PMID- 17863270 TI - RECENT TRAUMATIC DISLOCATIONS OF THE HIP: WITH A REPORT OF TEN CASES AND THEIR END RESULTS. PMID- 17863272 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 8, 1914: Stated Meeting, Held April. PMID- 17863269 TI - ONE HUNDRED AND TEN CONSECUTIVE CASES OF APPENDICITIS WITHOUT MORTALITY. PMID- 17863273 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 6, 1914: Stated Meeting, Held April. PMID- 17863271 TI - THE SIGNIFICANCE OF THE JACKSON VEIL. PMID- 17863274 TI - BILIARY SURGERY: FROM JANUARY, 1910, TO APRIL 10, 1914, WITH AN ANALYSIS OF 270 CASES. PMID- 17863276 TI - CYSTIC LYMPHANGIOMA OF THE GREAT OMENTUM. PMID- 17863275 TI - RETENTION CYSTS OF THE PANCREAS. PMID- 17863277 TI - PRIAPISM: REPORT OF CASES AND A CLINICAL STUDY OF THE LITERATURE WITH REFERENCE TO ITS PATHOGENESIS AND SURGICAL TREATMENT. PMID- 17863268 TI - INDICATIONS FOR AND VARIATIONS IN THE TECHNIC OF ECK FISTULA. PMID- 17863278 TI - RUPTURE OF THE BLADDER: REPORT OF AN UNUSUAL CASE. PMID- 17863280 TI - HYDRONEPHROSIS: AN EXPERIMENTAL STUDY. PMID- 17863282 TI - CONGENITAL MALFORMATION OF THE POSTERIOR URETHRA. PMID- 17863281 TI - PYELOGRAPHY IN THE DIAGNOSIS OF TRAUMATIC INJURY OF THE KIDNEY. PMID- 17863279 TI - OPERATIVE TREATMENT OF ACUTE EPIDIDYMITIS. PMID- 17863283 TI - CIRCULATORY AND TROPHIC DISTURBANCES OF THE EXTREMITIES: AN ATTEMPT AT CLASSIFICATION. PMID- 17863286 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held at the New York Academy of Medicine, 17 West Forty-third Street, Wednesday, May 13, 1914. PMID- 17863285 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held at the New York Academy of Medicine, April 22, 1914. PMID- 17863284 TI - CINEMATOPLASTIC AMPUTATIONS. PMID- 17863287 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting held May 4, 1914. PMID- 17863290 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held at the New York Academy of Medicine, October 28, 1914. PMID- 17863288 TI - THE CANCER PROBLEM. PMID- 17863291 TI - ALUM CREAM: THE IDEAL RUBBER GLOVE LUBRICANT. PMID- 17863289 TI - CONTRIBUTION TO THE STUDY OF THE STRUCTURE OF ENCEPHALOCYSTOCELE. PMID- 17863292 TI - REPORT OF A CASE OF PURE MYXOMA OF THE BREAST. PMID- 17863293 TI - THE OBLIQUE EXTENSOR RADIAL RIDGE. PMID- 17863294 TI - CALCIFIED FIBRO-ADENOMA OF BREAST. PMID- 17863295 TI - OBSERVATIONS ON CEREBRAL SURGERY. PMID- 17863296 TI - LARYNGEAL DIVERTICULA. PMID- 17863297 TI - THE RONTGENOLOGIC DIAGNOSIS OF SURGICAL LESIONS OF THE STOMACH AND DUODENUM. PMID- 17863300 TI - FRACTURE OF THE TIP OF THE INTERNAL CONDYLE OF THE FEMUR: LOOSE BODY IN THE KNEE JOINT. PMID- 17863298 TI - INFLUENCE OF INHALATION ANAESTHESIA ON THE ACIDITY OF THE BLOOD AS DETERMINED BY ESTIMATION OF H-ION CONCENTRATION. PMID- 17863301 TI - JOINT MOUSE. PMID- 17863299 TI - PERSISTENT EMBRYONAL TYPE OF LARGE INTESTINE. PMID- 17863302 TI - KELOID FORMATION IN THE NEGRO. PMID- 17863303 TI - FIXATION OF SIMPLE FRACTURES. PMID- 17863304 TI - TENDON FIXATION FOR DEFORMITY RESULTING FROM PARTIAL PARALYSIS. PMID- 17863306 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held at the New York Academy of Medicine, October 14, 1914. PMID- 17863305 TI - BLOOD-VESSEL CLAMPS OF PRACTICAL UTILITY. PMID- 17863309 TI - A PRELIMINARY REPORT ON A STUDY OF THE PROTECTIVE FERMENTS OF THE BLOOD BY THE ABDERHALDEN METHOD, AFTER THE TRANSPLANTATION OF ORGANS. PMID- 17863308 TI - MULTIPLE CONGENITAL OSTEOCHONDROMATA. PMID- 17863307 TI - CANCELLOUS BONE LESIONS: NON-TUBERCULOUS, NON-SYPHILITIC, NON-SUPPURATIVE, NON MALIGNANT. PMID- 17863310 TI - SPINA BIFIDA: AN EXPERIMENTAL AND CLINICAL STUDY. PMID- 17863311 TI - DEVELOPMENTAL RECONSTRUCTION OF THE COLON BASED ON SURGICAL PHYSIOLOGY. PMID- 17863312 TI - COLOCOLOSTOMY: A PRELIMINARY REPORT ON AN OPERATION FOR THE CONSERVATIVE RELIEF OF THE SYMPTOMS OF COLOPTOSIS AND COLOSTASIS. PMID- 17863313 TI - DUODENOTOMY IN COMMON DUCT STONE. PMID- 17863314 TI - THE MORTALITY STATISTICS OF TWO HUNDRED AND SEVENTY-SIX CASES OF ACUTE INTESTINAL OBSTRUCTION. PMID- 17863315 TI - PRESERVATION OF THE ILIOHYPOGASTRIC NERVE IN OPERATION FOR CURE OF INGUINAL HERNIA. PMID- 17863316 TI - COMPLETE FRACTURE OF THE LOWER THIRD OF THE RADIUS IN CHILDHOOD, WITH GREENSTICK FRACTURE OF THE ULNA. PMID- 17863317 TI - THE REFORMATION OF GALL-STONES AFTER OPERATION. PMID- 17863319 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, Monday evening, October 5, 1914. PMID- 17863318 TI - DOUBLE INTERNAL JUGULAR VEIN-HIGH BIFURCATION OF COMMON CAROTID ARTERY. PMID- 17863320 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held at the New York Academy of Medicine, November 11, 1914. PMID- 17863321 TI - TONSILLECTOMY IN CHILDREN FROM THE STAND-POINT OF THE GENERAL SURGEON. PMID- 17863323 TI - THE SURGICAL ANATOMY OF THE UPPER AND LOWER POLES OF THE THYROID GLAND WITH REFERENCE TO THYROIDECTOMY. PMID- 17863322 TI - MECHANISM OF THE PRODUCTION OF HEMORRHAGIC EROSIONS OF THE OESOPHAGUS AND OF SOME ASSOCIATED LESIONS IN ILEUS. PMID- 17863324 TI - URETERO-ENTERIC ANASTOMOSIS: A NEW ENTERO-URETERAL OPERATION AN INDUCTIVE STUDY BASED ON SURGICAL PHYSIOLOGY. PMID- 17863326 TI - ON THE LYMPHATIC DRAINAGE OF THE PERITONEAL SAC. PMID- 17863325 TI - STUDIES IN OBSCURE FORMS OF PROSTATIC OBSTRUCTION AND VESICAL ATONY. PMID- 17863328 TI - THE TECHNIC OF CHOLECYSTECTOMY. PMID- 17863330 TI - A STUDY OF MULTILOCULAR CYSTADENOMATA OF RETROPERITONEAL ORIGIN. PMID- 17863329 TI - SOME EXPERIMENTS ON THE SURGERY OF THE PANCREAS. PMID- 17863332 TI - SECONDARY ULCERS OF THE STOMACH AND JEJUNUM. FORMATION OF CALCULI AROUND UNABSORBABLE MATERIAL USED IN SUTURING THE INTESTINAL MUCOSA. PMID- 17863333 TI - CLINICAL ASPECTS OF COLON STASIS. PMID- 17863327 TI - THE PREVENTION OF POST-OPERATIVE ADHESIONS IN THE PERITONEAL CAVITY. PMID- 17863331 TI - THE SURGICAL SIGNIFICANCE OF INTESTINAL ANGIONEUROTIC OEDEMA: WITH AN ILLUSTRATIVE CASE. PMID- 17863336 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, November 2, 1914. PMID- 17863335 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, Held at the New York Academy of Medicine, November 25, 1914. PMID- 17863334 TI - THE RONTGENOLOGIC FINDINGS IN THREE CASES OF DIVERTICULITIS OF THE LARGE BOWEL. PMID- 17863337 TI - CORRESPONDENCE. PMID- 17863338 TI - THE RED STIPPLING SIGN OF GASTRIC AND DUODENAL ULCER. PMID- 17863339 TI - BILATERAL CONGENITAL ABSENCE OF THE RADIUS. PMID- 17863340 TI - STRANGULATED INGUINAL HERNIA CONTAINING CAECUM AND APPENDIX. PMID- 17863341 TI - ENDOTHELIOMA OF THE INTERCAROTID BODY. PMID- 17863342 TI - THE OPERATIVE TREATMENT OF CARCINOMA OF THE OESOPHAGUS. PMID- 17863345 TI - OCCLUSION OF THE PYLORUS. PMID- 17863343 TI - GASTRIC AND DUODENAL ULCER: A REVIEW OF 120 CASES OPERATED UPON AT THE ROOSEVELT HOSPITAL BY THE SURGICAL STAFF DURING THE PAST FIVE YEARS. PMID- 17863344 TI - ON RETROPERITONEAL PERFORATION OF DUODENAL ULCER. PMID- 17863346 TI - APPENDICULAR OBLITERATION. PMID- 17863347 TI - THE MAJOR PROCEDURE FIRST IN THE TWO-STAGE OPERATION FOR RELIEF OF CANCER OF THE RECTUM. PMID- 17863350 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held at the New York Academy of Medicine, December 9, 1914. PMID- 17863348 TI - PAINFUL SUBCUTANEOUS TUBERCLE. PMID- 17863349 TI - TYPHOID SPINE: WITH REPORT OF FOUR CASES. PMID- 17863351 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held January 13, 1915. PMID- 17863352 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, December 7, 1914. PMID- 17863353 TI - BLASTOMYCOSIS. PMID- 17863354 TI - THE OPERATIVE TREATMENT OF ARTERIAL THROMBOSIS AND EMBOLISM. PMID- 17863355 TI - GALL-STONES: A STATISTICAL STUDY OF CASES OCCURRING AT THE BOSTON CITY HOSPITAL. PMID- 17863356 TI - THE SURGICAL TREATMENT OF GASTROCOLOPTOSIS. PMID- 17863357 TI - THE ROLE OF GASTRO-ENTEROSTOMY IN THE TREATMENT OF ULCERS. PMID- 17863359 TI - THE PATHOGENESIS OF UMBILICAL HERNIA. PMID- 17863358 TI - THE ACTIVITY OF THE PYLORUS FOLLOWING GASTRO-ENTEROSTOMY. PMID- 17863360 TI - CYSTIC DILATION OF THE VERMIFORM APPENDIX. PMID- 17863361 TI - PYLEPHLEBITIS COMPLICATING APPENDICITIS. PMID- 17863362 TI - A NEW METHOD OF LATERAL ANASTOMOSIS OF BLOOD-VESSELS AND AN OPERATION FOR THE CURE OF ARTERIOVENOUS ANEURISM. PMID- 17863363 TI - THE "TONGUE-DEPRESSOR" GASTRO-ENTEROSTOMY CLAMP. PMID- 17863364 TI - THE PREVENTION OF KELOIDS IN SCARS BY THE UNDER-LINING OF INCISIONS WITH STRIPS OF FASCIA LATA. PMID- 17863365 TI - RUPTURE OF THE BICEPS FLEXOR CUBITI: WITH A REPORT OF EIGHT CASES. PMID- 17863367 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held at the New York Academy of Medicine, January 27, 1915. PMID- 17863366 TI - THE USEFULNESS OF VENTRAL DECUBITUS IN SOME LEG AMPUTATIONS. PMID- 17863368 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, January 4, 1915. PMID- 17863370 TI - TRANSPLANTATION OF ENTIRE BONES WITH THEIR JOINT SURFACES. PMID- 17863369 TI - LIGATURE OF THE INNOMINATE ARTERY FOR CURE OF SUBCLAVIAN ANEURISMS. PMID- 17863371 TI - THE OSTEOGENIC POWER OF PERIOSTEUM: WITH A NOTE ON BONE TRANSPLANTATION: AN EXPERIMENTAL STUDY. PMID- 17863372 TI - GUNSHOT INJURIES OF THE SPINAL CORD: A PRELIMINARY REPORT UPON FIVE CASES. PMID- 17863373 TI - PERFORATING GUNSHOT WOUNDS OF THE ABDOMEN: REMARKS ON A CONSECUTIVE SERIES OF TWENTY-SEVEN CASES WITH THREE DEATHS. PMID- 17863374 TI - FRACTURE OF THE PELVIS: SYMPTOMS AND CLINICAL COURSE FROM A STUDY OF TWENTY-NINE CASES. PMID- 17863376 TI - AUTOGENOUS BONE GRAFTS VERSUS LANE'S PLATES. PMID- 17863375 TI - SIMULTANEOUS FRACTURE OF BOTH FEMURS: ONE TREATED BY PLATING, THE OTHER BY EXTENSION AND PLASTER-OF-PARIS CASE. PMID- 17863378 TI - OCCULT STRANGULATED INGUINAL HERNIA; SPONTANEOUS REDUCTION "EN MASSE". PMID- 17863377 TI - PAPILLOMA OF THE GALL-BLADDER: REPORT OF 85 CASES. PMID- 17863379 TI - THE TREATMENT OF BENIGN PAPILLOMATA OF THE URINARY BLADDER WITH HIGH FREQUENCY CURRENTS. PMID- 17863380 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, Held February 10, 1915. PMID- 17863381 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, February 1, 1915. PMID- 17863383 TI - NOTES ON MILITARY SURGERY. PMID- 17863382 TI - A LEAD PROTECTOR FOR USE IN BONE WORK. PMID- 17863384 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held March 10, 1915, at the New York Academy of Medicine. PMID- 17863385 TI - SARCOMA OF THE BREAST. PMID- 17863386 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held March 1, 1915. PMID- 17863388 TI - CARCINOMA OF THE STOMACH. PMID- 17863387 TI - THE CAMPAIGN AGAINST CANCER. PMID- 17863389 TI - LEATHER-BOTTLE STOMACH: WITH REPORT OF A CASE IN WHICH SUBTOTAL GASTRECTOMY WAS DONE. PMID- 17863391 TI - PERIENTERITIS MEMBRANOSA: A FURTHER CONTRIBUTION TO THE SUBJECT OF PERICOLITIS, JACKSON'S VEIL, ETC., IN THE LIGHT OF A POST-MORTEM OBSERVATION. PMID- 17863390 TI - CANCER OF THE TESTIS: CONTAINING A REPORT OF 64 CASES, WITH SPECIAL REFERENCE TO 12 CASES OF CANCER OF THE UNDESCENDED TESTIS. PMID- 17863392 TI - THE BONE GRAFT PEG IN THE TREATMENT OF FRACTURES OF NECK OF FEMUR: AUTHOR'S TECHNIC. PMID- 17863393 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held February 24, 1915. PMID- 17863394 TI - SURGERY AND WAR: ADDRESS OF THE PRESIDENT AT THE OPENING OF THE SESSION OF THE AMERICAN SURGICAL ASSOCIATION, JUNE 9, 1915. PMID- 17863395 TI - THE INCIDENCE OF HEREDITY AS A FACTOR IN THE CAUSATION OF GOITRE. PMID- 17863396 TI - LAPAROTOMY IN TYPHOID FEVER. PMID- 17863397 TI - ACUTE APPENDICITIS OCCURRING IN THE COURSE OF TYPHOID FEVER. PMID- 17863399 TI - PATHOLOGY OF SPLEENS REMOVED FOR CERTAIN ABNORMAL CONDITIONS OF THE BLOOD: PRELIMINARY REPORT. PMID- 17863398 TI - ACUTE CHOLECYSTITIS COMPLICATING TYPHOID FEVER. PMID- 17863400 TI - CLINICAL NOTES ON SPLENECTOMY. PMID- 17863402 TI - CAVERNOUS ANGIOMA OF THE SPLEEN. PMID- 17863401 TI - SURGICAL CONSIDERATIONS OF SPLENECTOMY. PMID- 17863403 TI - ABSCESS OF THE SPLEEN. PMID- 17863404 TI - PAPILLOMAS OF THE GALL-BLADDER. PMID- 17863405 TI - A REPORT OF THE CASES OF GALL-STONE DISEASE OPERATED DURING THE YEAR 1914. PMID- 17863406 TI - FISTULOUS COMMUNICATION BETWEEN THE STOMACH AND COLON, FOLLOWING GASTRO ENTEROSTOMY. PMID- 17863407 TI - PAGET'S DISEASE OF THE NIPPLE AND ALLIED CONDITIONS. PMID- 17863408 TI - ON EXCISION OF THE TONGUE. PMID- 17863410 TI - AMPUTATION OF THE BREAST BY A TRANSVERSE INCISION. PMID- 17863409 TI - CONSERVATIVE OPERATIONS IN CYSTS OF THE BREAST. PMID- 17863411 TI - NON-CALCULOUS OBSTRUCTION OF THE UPPER URETER. PMID- 17863413 TI - THE PHENOMENA OF ACIDOSIS AND ITS DOMINATING INFLUENCE IN SURGERY. PMID- 17863412 TI - DR. DEPAGE'S LETTER OF APPRECIATION TO AMERICAN SURGEONS. PMID- 17863414 TI - END RESULTS OF BONE FRACTURES: Report of the Committee of the American Surgical Association. PMID- 17863415 TI - AUTOPLASTIC REPAIR OF FRACTURES OF NECK OF THE FEMUR. PMID- 17863416 TI - EXTENSION AND REDUCTION OF TRANSVERSE OR SERRATED FRACTURES OF THE FEMUR. PMID- 17863417 TI - NOTES ON FRACTURES. PMID- 17863418 TI - ON FRACTURES OF THE SESAMOID BONES OF THE THUMB. PMID- 17863419 TI - ARTHROPLASTY OF THE ELBOW. PMID- 17863421 TI - BANTI'S SYMPTOM COMPLEX WITH RELATION TO SPLENECTOMY. PMID- 17863420 TI - EMPYEMA: EXPLORATION OF THE THORAX WITH PRIMARY MOBILIZATION OF THE LUNG. PMID- 17863422 TI - CHRONIC INTESTINAL STASIS AS PRODUCED BY OBSTRUCTION AT THE ILEOCAECAL REGION AND AT THE HEPATIC FLEXURE: WITH REPORT OF NINETEEN CASES. PMID- 17863423 TI - DIPHTHERIAL AND PSEUDODIPHTHERIAL PRIMARY CUTANEOUS INFECTION. PMID- 17863424 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held March 24, 1915. PMID- 17863425 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held April 14, 1915. PMID- 17863426 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting April 5, 1915. PMID- 17863428 TI - RUPTURE OF BICEPS FLEXOR CUBITI. PMID- 17863427 TI - POST-OPERATIVE BACKACHE. PMID- 17863429 TI - THE UTILITY OF THE FATTY CAPSULE IN THE OPERATION OF NEPHROPEXY. PMID- 17863430 TI - TYPHOID PERFORATION: A STUDY OF 139 CASES AND 16 SUPPOSED CASES OCCURRING IN THE PENNSYLVANIA HOSPITAL. PMID- 17863431 TI - THE TREATMENT OF JOINT INFECTIONS BY LAVAGE AND DIRECT MEDICATION. PMID- 17863432 TI - ACUTE GANGRENE OF THE GALL-BLADDER FOLLOWING INJURY. PMID- 17863433 TI - SITUS VISCERUM INVERSUS WITH GALL-STONES. PMID- 17863434 TI - CARCINOMA OF THE SMALL INTESTINE: WITH THE REPORT OF A CASE EACH OF THE JEJUNUM AND OF THE ILEUM. PMID- 17863435 TI - DILATATION OF THE DUODENUM: AN EXPERIMENTAL STUDY. PMID- 17863436 TI - CONTRIBUTION TO THE SURGICAL PHYSIOLOGY OF THE COLON. PMID- 17863437 TI - THE TRIANGLE OF PETIT IN KIDNEY SURGERY. PMID- 17863438 TI - OPERATIVE TREATMENT OF TUMORS OF THE BLADDER: CLINICAL RESULTS AS OBTAINED FROM A REVIEW OF 1702 CASES OF OPERATIONS ON TUMORS OF THE BLADDER BY VARIOUS OPERATORS DURING THE LAST FIFTEEN YEARS. PMID- 17863439 TI - SUPRAPUBIC PROSTATECTOMY IN TWO STAGES. PMID- 17863440 TI - PRIMARY TUBERCULOSIS OF THE PROSTATE GLAND. PMID- 17863441 TI - PATHOLOGIC LESIONS OBSERVED IN THE POSTERIOR MALE URETHRA BY MEANS OF THE URETHROSCOPE: AS SHOWN BY A SERIES OF PHOTOGRAPHS FROM WAX MODELS. PMID- 17863442 TI - A MODE FOR VENTROFIXATION OF THE UTERUS FOR THE RELIEF OF PROLAPSUS. PMID- 17863443 TI - TENDON FIXATION IN INFANTILE PARALYSIS: OBSERVATIONS BASED ON ONE HUNDRED OPERATIONS. PMID- 17863444 TI - CORRECTIVE OTOPLASTY: A REPORT OF TWO CASES. PMID- 17863445 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held April 28, 1915. PMID- 17863446 TI - MESENTERIC THROMBOSIS. PMID- 17863447 TI - A REPORT UPON ONE CASE OF SPLENECTOMY. PMID- 17863448 TI - THE DIAGNOSIS OF APPENDICITIS IN EARLY TYPHOID FEVER. PMID- 17863450 TI - FREQUENCY OF CHEST COMPLICATIONS AMONG THE WOUNDED. PMID- 17863449 TI - TYPHOID PERFORATION. PMID- 17863451 TI - THE TRANSVERSE ABDOMINAL INCISION. PMID- 17863452 TI - THE CLOSURE OF MUCOCUTANEOUS FECAL FISTULAE. PMID- 17863453 TI - AN ANATOMICAL STUDY OF FEMORAL HERNIA: TOGETHER WITH A REPORT OF SIX CASES OF INGUINAL HERNIA OF SPECIAL INTEREST THREE WITH PROTRUSION OF THE BLADDER. PMID- 17863454 TI - THE CLINICAL STATUS OF THE AUTOGRAFT. PMID- 17863456 TI - END RESULTS IN FRACTURES OF BOTH BONES OF THE LEG. PMID- 17863455 TI - FRACTURES OF THE FEMUR: WITH END RESULTS IN 62 CASES. PMID- 17863457 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held May 12, 1915. PMID- 17863458 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, May 3, 1915. PMID- 17863459 TI - HAEMANGIOMA OF THE SPINAL CORD: ASSOCIATED WITH SKIN NAEVI OF THE SAME METAMERE. PMID- 17863461 TI - SUPPURATIVE PERICARDITIS. PMID- 17863460 TI - THE CONSERVATIVE TREATMENT OF INTRINSIC CANCER OF THE LARYNX BY THYREOCRICOTOMY (TOTAL LARYNGOFISSURE) OR THYROTOMY (PARTIAL LARYNGOFISSURE). PMID- 17863463 TI - SPLENECTOMY FOR SPLENIC ANAEMIA IN CHILDHOOD AND FOR THE SPLENIC ANAEMIA OF INFANCY. PMID- 17863462 TI - THE ABDOMINAL SKIN-FLAP IN RADICAL AMPUTATION OF THE BREAST. PMID- 17863464 TI - PRIMARY SARCOMA OF THE GALL-BLADDER. PMID- 17863466 TI - OBTURATOR HERNIA: WITH REPORT OF CASE. PMID- 17863465 TI - RESECTION OF THE CARDIA FOR CARCINOMA. PMID- 17863467 TI - THE PROSTATE GLAND IN OLD AGE. PMID- 17863469 TI - FASCIA TRANSPLANTATION IN THE TREATMENT OF OLD FRACTURES OF THE PATELLA. PMID- 17863470 TI - DECOMPRESSION UNDER LOCAL ANAESTHESIA. PMID- 17863468 TI - GIANT-CELL TUMORS OF THE TENDON SHEATHS. PMID- 17863472 TI - GAS BACILLUS INFECTION. PMID- 17863471 TI - THE ACTION OF RADIUM ON TRANSPLANTED TUMORS OF ANIMALS. PMID- 17863474 TI - A METHOD FOR OBTAINING UNCONTAMINATED BLOOD FROM DOGS AND OTHER ANIMALS. PMID- 17863473 TI - REPAIR OF SMALL VESICOVAGINAL FISTULA. PMID- 17863475 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held October 13, 1915. PMID- 17863476 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held October 27, 1915. PMID- 17863477 TI - CHOLECYSTOSTOMY AND CAECOSTOMY FOR MERCURY BICHLORIDE POISONING. PMID- 17863479 TI - PRIMARY NEOPLASMS OF THE LYMPHATIC GLANDS INCLUDING HODGKIN'S DISEASE. PMID- 17863478 TI - THE SIGNIFICANCE OF FOREIGN BODIES IN THE TISSUES. PMID- 17863480 TI - CONCERNING THE SURGICAL ANATOMY OF THE THYROID WITH SPECIAL REFERENCE TO THE PARATHYROID GLANDS. PMID- 17863482 TI - THE USE OF FREE OMENTAL GRAFTS IN ABDOMINAL SURGERY. PMID- 17863481 TI - NON-STRANGULATED DIAPHRAGMATIC HERNIA DUE TO INDIRECT INJURY. PMID- 17863483 TI - ON LIGATION OF SPLENIC VESSELS AS A SUBSTITUTE FOR SPLENECTOMY IN BLOOD DISEASES: ALSO A CONTRIBUTION TO THE PATHOLOGY OF THE INFARCTS OF THE SPLEEN. PMID- 17863484 TI - STUDIES ON THE LOCALIZATION OF CEREBELLAR TUMORS: THE POSITION OF THE HEAD AND SUBOCCIPITAL DISCOMFORTS. PMID- 17863485 TI - CALCULI IN THE SUBMAXILLARY GLAND AND WHARTON'S DUCT. PMID- 17863486 TI - TUBERCULOSIS OF THE TONGUE. PMID- 17863487 TI - TANNERS' ULCER: CHROME SORES-CHROME HOLES-ACID BITES. PMID- 17863488 TI - MULTIPLE CARTILAGINOUS EXOSTOSES (HEREDITARY DEFORMING CHONDRODYSPLASIA): WITH NOTES OF NINE HITHERTO UNPUBLISHED CASES. PMID- 17863489 TI - TREATMENT OF VARICOSE LEG ULCERS. PMID- 17863490 TI - THE ARTIFICIAL PERIOSTEUM FOR FIXATION OF SHAFT FRACTURES. PMID- 17863491 TI - HOMOPLASTIC TRANSPLANTATION OF A BOILED SEGMENT OF A RADIUS: RESULT AFTER THREE AND A HALF YEARS. PMID- 17863492 TI - A SYMMETRICAL CONGENITAL MALFORMATION OF THE EXTREMITIES: WITH A REPORT OF TWO CASES. PMID- 17863493 TI - PERITONEAL ADHESIONS: THEIR PREVENTION WITH CITRATE SOLUTIONS. PMID- 17863494 TI - THE PREVENTION OF PERITONEAL ADHESIONS BY THE USE OF CITRATE SOLUTION. PMID- 17863495 TI - REMARKS ON THE SURGERY OF THE EUROPEAN WAR: WITH A DESCRIPTION OF AN IRRIGATION SYSTEM FOR PERFORATING INFECTED WOUNDS. PMID- 17863496 TI - FRACTURES OF THE NECK OF THE SCAPULA. PMID- 17863497 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held October 4, 1915. PMID- 17863498 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held November 1, 1915. PMID- 17863499 TI - THE CLASSIFICATION OF TUMORS. PMID- 17863500 TI - ACUTE DILATATION OF THE STOMACH COMPLICATING OPERATIONS ON THE EXTREMITIES. PMID- 17863502 TI - THE CONSERVATIVE TREATMENT OF GANGRENE OF THE EXTREMITIES DUE TO THROMBO-ANGIITIS OBLITERANS. PMID- 17863501 TI - REVERSAL OF THE CIRCULATION IN THE LOWER EXTREMITY. PMID- 17863503 TI - HYPOPHYSIAL DISORDER IN MAMMARY CANCER AND ITS RELATION TO DIABETES INSIPIDUS. PMID- 17863505 TI - TOLUOL: ITS ADVANTAGES OVER CHLOROFORM OR ALCOHOL AS A STORING FLUID FOR SURGICAL CATGUT. PMID- 17863504 TI - THE USE OF WARMED ETHER VAPOR FOR ANAESTHESIA. PMID- 17863507 TI - THE ANATOMICAL AND PHYSIOLOGICAL SUBDIVISIONS OF THE DUODENUM, WITH A NOTE UPON THE PATHOGENESIS OF ULCER: A PLEA FOR THE RATIONAL CLASSIFICATION OF DUODENAL LESIONS. PMID- 17863506 TI - ACUTE SECONDARY TUBERCULOUS SPLENOMEGALY: SPLENECTOMY. PMID- 17863508 TI - ULCER OF THE DUODENOPYLORIC FORNIX. PMID- 17863510 TI - MEGACOLON: HIRSCHSPRUNG'S DISEASE-REPORT OF A CASE IN AN ADULT. PMID- 17863509 TI - CYSTIC DILATATION OF THE VERMIFORM APPENDIX: REPORT OF A CASE OF HYDROPIC CYST, WITH A STUDY OF 142 CASES. PMID- 17863511 TI - SIGMOIDOVESICAL FISTULA: WITH REPORT OF A CASE. PMID- 17863512 TI - A STITCH TO ASSIST IN THE CLOSURE OF THE POSTERIOR SHEATH OF THE RECTUS ABOVE DOUGLAS'S SEMILUNAR FOLD. PMID- 17863513 TI - ARTIFICIAL IMPACTION OF HIP FRACTURE. PMID- 17863514 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held December 6, 1915. PMID- 17863515 TI - ACIDOSIS IN SURGERY: A REVIEW OF 138 CONSECUTIVE MAJOR OPERATIVE CASES, IN WHICH THE DOMINATING INFLUENCE OF ACIDOSIS WAS CONSIDERED. PMID- 17863516 TI - PULSATING EXOPHTHALMOS: WITH REPORT OF A CASE CURED BY LIGATION OF COMMON CAROTID ARTERY. PMID- 17863517 TI - OPERATION FOR REMOVING THE GALL-BLADDER. PMID- 17863519 TI - THE INEFFICACY OF PYLORIC EXCLUSION BY FASCIAL BANDS: AN EXPERIMENTAL STUDY. PMID- 17863518 TI - ACUTE OPERATIVE DILATATION OF THE STOMACH: REPORT OF A FATAL CASE AT THE TERMINATION OF GASTRO-ENTEROSTOMY FOR CHRONIC DUODENAL ULCER: FIVE ADDITIONAL CASES OF OPERATIVE DILATATION COLLECTED FROM THE LITERATURE: A SPECIAL STUDY OF THE ETIOLOGY OF ACUTE OPERATIVE AND POST-OPERATIVE GASTRIC DILATATION. PMID- 17863521 TI - THE PREVENTION OF FECAL FISTULA IN SUPPURATIVE APPENDICITIS. PMID- 17863520 TI - POST-OPERATIVE INTESTINAL OBSTRUCTION. PMID- 17863522 TI - RECENT CLINICAL AND PATHOLOGICAL OBSERVATIONS ON GIANT-CELL MEDULLARY BONE TUMORS. PMID- 17863523 TI - THE TRANSPLANTATION OF BONE IN UNUNITED FRACTURES OF THE SHAFT OF THE HUMERUS. PMID- 17863524 TI - OSTEOMYELITIS INVOLVING THE HIP-JOINT: A CONDITION HERETOFORE ERRONEOUSLY DESIGNATED ACUTE EPIPHYSITIS. PMID- 17863525 TI - THE LEGAL RESPONSIBILITY TO THE SURGEON AND PRACTITIONER WHICH THE USE OF THE X RAY INVOLVES. PMID- 17863527 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held January 12, 1916. PMID- 17863526 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held December 8, 1915. PMID- 17863529 TI - REPAIR OF VESICOVAGINAL FISTULA. PMID- 17863528 TI - THE ROLE OF ABDUCTION IN THE TREATMENT OF HIP FRACTURES AS COMPARED WITH ARTIFICIAL IMPACTION. PMID- 17863530 TI - SUGGESTED OPERATIVE STEPS DEALING WITH SPONTANEOUS INTRACEREBRAL HEMORRHAGE (APOPLEXY). PMID- 17863531 TI - COMPLETE BRANCHIOGENIC FISTULA. PMID- 17863532 TI - THE SURGICAL TREATMENT OF SUPPURATIONS IN THE POSTERIOR MEDIASTINUM. PMID- 17863533 TI - REMOVAL OF BULLET FROM PERICARDIUM: REPORT OF A CASE. PMID- 17863535 TI - A METHOD OF CORRECTING THE STOMACH DILATATION IN GASTROPTOSIS. PMID- 17863534 TI - INTRAHEPATIC CHOLELITHIASIS. PMID- 17863537 TI - LUMBAR HERNIA. PMID- 17863536 TI - THE ETIOLOGY OF CYSTS CONNECTED WITH HERNIAL SACS. PMID- 17863538 TI - ON PERFORATING AND VARICOSE ULCERS OF THE LEG AND THEIR TREATMENT BY NERVE OPERATIONS. PMID- 17863540 TI - TREATMENT OF INJURIES IN THE VICINITY OF THE ELBOW-JOINT. PMID- 17863539 TI - A PLEA FOR THE IMMEDIATE REDUCTION OF FRACTURES. PMID- 17863541 TI - FRACTURE-DISLOCATION OF THE ASTRAGALUS: TREATMENT BY REDUCTION THROUGH OPEN INCISION. PMID- 17863543 TI - DOUBLE UTERUS AND VAGINA WITH A NEW BLOODLESS OPERATION FOR THE CORRECTION OF THE DEFORMITY. PMID- 17863542 TI - A SIMPLIFIED PRE-OPERATIVE TREATMENT OF THE HANDS AND FIELD OF OPERATION. PMID- 17863544 TI - INDEX OF TOXICITY OF NOVOCAINE-ADRENALIN INJECTED INTRAVENOUSLY. PMID- 17863545 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held January 3, 1916. PMID- 17863546 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held January 26, 1916. PMID- 17863547 TI - THE TREATMENT OF FRACTURES BY METHODS OF SUSPENSION AND EXTENSION. PMID- 17863549 TI - TUBERCULOSIS OF THE BREAST: A REPORT OF 10 CASES. PMID- 17863548 TI - FOREIGN BODIES IN THE RESPIRATORY TRACT. PMID- 17863550 TI - A DENTAL PLATE IN THE OESOPHAGUS. PMID- 17863551 TI - THE APERIOSTEAL STUMP AND ITS CARE. PMID- 17863552 TI - A METHOD OF FACILITATING INFILTRATION ANAESTHESIA. PMID- 17863553 TI - CALCAREOUS DEGENERATION OF THE PROSTATE GLAND: REPORT OF A CASE. PMID- 17863554 TI - THE TECHNIC OF SUPRAPUBIC CYSTOSTOMY IN BADLY INFECTED CASES. PMID- 17863555 TI - SHIRRING THE ROUND LIGAMENTS: A NEW METHOD OF SHORTENING THE LIGAMENTS FOR RETRODISPLACEMENTS OF THE UTERUS. PMID- 17863556 TI - URETHROPLASTY AT THE BASE OF THE GLANS PENIS. PMID- 17863558 TI - THE TREATMENT OF THE RETROCAECAL APPENDIX. PMID- 17863557 TI - THE PATHOLOGICAL DIAGNOSIS OF DISEASES OF THE APPENDIX BASED ON THE STUDY OF 1500 SPECIMENS. PMID- 17863559 TI - HIGH INTESTINAL STASIS. PMID- 17863560 TI - EXPERIMENTAL COLONIC STASIS. PMID- 17863562 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held February 9, 1916. PMID- 17863561 TI - JEJUNAL ULCER, FOLLOWING GASTRO-ENTEROSTOMY FOR DUODENAL ULCER, WITH COMPLETE CLOSURE OF THE GASTRIC END OF THE STOMA. PMID- 17863563 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held February 23, 1916. PMID- 17863565 TI - BRANCHIOGENIC CARCINOMA. PMID- 17863564 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held February 7, 1916. PMID- 17863566 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held November 24, 1915. PMID- 17863567 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held March 8, 1916. PMID- 17863568 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held March 6, 1916. PMID- 17863570 TI - THE ELEMENT OF ERROR IN ABDOMINAL DIAGNOSIS. PMID- 17863569 TI - THE HANDLING OF CHILDREN WITH TUBERCULOSIS OF THE SPINE WHILE THEY ARE UNDER THE INFLUENCE OF AN ANAESTHETIC. PMID- 17863572 TI - CYSTS OF THE URACHUS: WITH REPORT OF A CASE. PMID- 17863571 TI - SURGERY OF THE GALL-BLADDER: WITH ESPECIAL REFERENCE TO CHANGES IN TECHNIC. PMID- 17863573 TI - A TRANSPLANTABLE CHONDRO-OSTEOSARCOMA IN A DOG. PMID- 17863574 TI - A TRACTION BANDAGE FOR REDUCTION OF FRACTURE OF THE LEG. PMID- 17863575 TI - THE SLIDING GRAFT AND THE KANGAROO SUTURE IN FRESH FRACTURES: ALBEE TECHNIC. PMID- 17863576 TI - FRACTURES OF THE FEMUR. PMID- 17863578 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held November 10, 1915. PMID- 17863577 TI - THE THERAPEUTICS OF CHRONIC NON-TUBERCULOUS SUPPURATIVE BRONCHIECTASIS. PMID- 17863580 TI - THE SURGICAL LESSONS OF THE EUROPEAN WAR. PMID- 17863579 TI - PREPAREDNESS: THE PRESIDENTIAL ADDRESS DELIVERED BEFORE AMERICAN SURGICAL ASSOCIATION, WASHINGTON, D. C., MAY 9, 1916. PMID- 17863581 TI - LOCALIZATION AND EXTRACTION OF PROJECTILES AND SHELL FRAGMENTS. PMID- 17863582 TI - METHODS OF HANDLING INJURIES ON TRANSPORTATION SYSTEMS AND WOUND TREATMENT. PMID- 17863583 TI - CHRONIC GENERAL INFECTION WITH THE BACILLUS PYOCYANEUS. PMID- 17863584 TI - A FURTHER NOTE ON ETIOLOGY OF SURGICAL SCARLATINA. PMID- 17863586 TI - OBSERVATIONS ON THE DIAGNOSIS AND TREATMENT OF TRIFACIAL NEURALGIA. PMID- 17863585 TI - MELANOTIC CANCER: WITH A REPORT OF 91 CASES. PMID- 17863587 TI - DISLOCATION OF THE FIRST CERVICAL VERTEBRA: UNILATERAL AND BACKWARD: PRODUCED BY MANIPULATION. PMID- 17863588 TI - A METHOD OF TREATING CYSTS OF THE BREAST. PMID- 17863589 TI - TUMORS OF THE CAROTID BODY. PMID- 17863591 TI - THE TECHNIC AND THE MANAGEMENT OF OPERATIONS ON THE STOMACH. PMID- 17863590 TI - TRANSVERSE INCISIONS IN THE UPPER ABDOMEN. PMID- 17863592 TI - MORE RADICAL TREATMENT OF DUODENAL AND GASTRIC ULCER. PMID- 17863594 TI - THE RADICAL OPERATION FOR CANCER OF THE RECTUM AND RECTOSIGMOID. PMID- 17863593 TI - RADIUM TREATMENT OF UTERINE CANCERS. PMID- 17863595 TI - SARCOMA OF THE APPENDIX. PMID- 17863596 TI - FRACTURES ABOUT THE WRIST IN CHILDHOOD AND ADOLESCENCE. PMID- 17863597 TI - UNDESCENDED TESTIS. PMID- 17863598 TI - ACUTE SUPPURATIVE PANCREATITIS. GANGRENE OF THE MAJOR PORTION OF THE PANCREAS. RECOVERY. DETERMINATION OF PANCREATIC FUNCTION THREE YEARS SUBSEQUENTLY. PMID- 17863599 TI - AMOEBIC ABSCESS OF THE LIVER. PMID- 17863600 TI - SYSTEM OF KEEPING SURGICAL RECORDS. PMID- 17863601 TI - A SURGICAL "FOLLOW-UP" SYSTEM. PMID- 17863602 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held March 23, 1916. PMID- 17863603 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held April 3, 1916. PMID- 17863604 TI - EXOPHTHALMIC GOITRE: IMPORTANT FEATURES FROM THE STAND-POINT OF THE CLINICAL SURGEON. PMID- 17863605 TI - THE SURGICAL TREATMENT OF GOITRE: HOW CAN THE RESULTS ACHIEVED BE IMPROVED? PMID- 17863606 TI - RESULTS OF OPERATIVE TREATMENT OF EXOPHTHALMIC GOITRE. PMID- 17863607 TI - THE SURGICAL TREATMENT OF PERFORATED ULCER OF THE STOMACH: WITH ESPECIAL REFERENCE TO THE QUESTION OF IMMEDIATE GASTRO-ENTEROSTOMY. PMID- 17863608 TI - A REPORT OF NINE CONSECUTIVE OPERATIONS FOR PERFORATED GASTRIC AND DUODENAL ULCERS. PMID- 17863610 TI - ANOMALIES OF THE GALL-BLADDER AND BILE-PASSAGES: WITH THE REPORT OF A DOUBLE GALL BLADDER AND A FLOATING GALL-BLADDER. PMID- 17863609 TI - RUPTURE OF THE COMMON BILE-DUCT ASSOCIATED WITH SUBPHRENIC ABSCESS. PMID- 17863611 TI - THE INTERPRETATION OF FUNCTIONAL RENAL TESTS WITH SPECIAL REFERENCE TO THE SIGNIFICANCE OF MINIMAL EXCRETION OF PHTHALEIN AND INDIGO-CARMIN. PMID- 17863612 TI - TRAUMATIC INJURIES OF THE KIDNEY AND URETER. PMID- 17863613 TI - OS CALCIS FRACTURE. PMID- 17863614 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held May 8, 1916. PMID- 17863615 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held April 12, 1916. PMID- 17863616 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held April 27, 1916. PMID- 17863617 TI - EPITHELIOMA IMMEDIATELY FOLLOWING SINGLE BURN. PMID- 17863618 TI - TOTAL BONE GRAFTS INTO SKULL DEFECTS. PMID- 17863619 TI - PARTIAL EPIPHYSIAL TRANSPLANTATION FOR DEFECT IN FIBULA: REPORT OF CASE UNDER OBSERVATION OVER FIVE YEARS. PMID- 17863620 TI - VENOUS ANEURISMAL VARIX. PMID- 17863621 TI - SEGMENTAL RESECTION FOR GASTRIC ULCER: A PRELIMINARY REPORT BASED UPON CLINICAL AND EXPERIMENTAL STUDIES. PMID- 17863623 TI - CHOLEDOCHUS CYST: REPORT OF A CASE WITH REFERENCES TO THE LITERATURE. PMID- 17863622 TI - INTRAPARENCHYMATOUS HEMORRHAGE OF THE SPLEEN: HEMORRHAGIC SPLENITIS: INTRASPLENIC HAEMATOMA (NON-TRAUMATIC); APOPLEXY OF THE SPLEEN: FIBRINOUS TRANSFORMATION OF SPLEEN. PMID- 17863624 TI - RETROPERITONEAL RUPTURE OF THE DUODENUM BY BLUNT FORCE. PMID- 17863625 TI - CHRONIC APPENDICITIS AND ITS RELATION TO VISCEROPTOSIS. PMID- 17863626 TI - PSEUDOMUCINOUS CYST OF THE APPENDIX COMPLICATING RUPTURED ECTOPIC GESTATION. PMID- 17863627 TI - CYSTIC DILATATION OF THE VERMIFORM APPENDIX. PMID- 17863628 TI - MAJOR SURGERY UNDER MINOR ANAESTHESIA. PMID- 17863629 TI - DEVICE FOR WARMING ETHER DURING INHALATION. PMID- 17863630 TI - RESULTS OBTAINED BY THE USE OF RADIUM IN THE TREATMENT OF CANCER OF THE UTERUS: AT THE UNIVERSITY OF PENNSYLVANIA HOSPITAL. PMID- 17863631 TI - THE FOUR-POST FRACTURE BEDSTEAD. PMID- 17863632 TI - SUPERNUMERARY MUSCLE OF THE DORSUM OF THE HAND: EXTENSOR BREVIS DIGITI MEDII ET INDICIS: A RARE CAUSE OF DISABILITY IN A PIANIST. PMID- 17863633 TI - THE IMPORTANCE OF THE PROPER DOSAGE OF SODIUM CITRATE IN BLOOD TRANSFUSION. PMID- 17863634 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, Held May 10, 1916. PMID- 17863635 TI - TISSUE FRAGMENTS AND WOUND INFECTION. PMID- 17863636 TI - BLOOD-PRESSURE AND GRAPHIC VASOMOTOR CHANGES IN THE PERIPHERY DURING ETHER ANAESTHESIA. PMID- 17863637 TI - BLOOD-PRESSURE AND PROSTATECTOMY. PMID- 17863638 TI - FURTHER OBSERVATIONS ON THE ANATOMY OF THE SINUS FRONTALIS IN MAN. PMID- 17863639 TI - TOOTH GERM CYSTS OF THE JAW. PMID- 17863640 TI - TWO CASES OF THORACIC ANEURISM WIRED FOUR YEARS AND THEREABOUTS AGO RESPECTIVELY: WITH REMARKS ON THE ANTISPECIFIC TREATMENT AND THE OPERATIVE TREATMENT OF THORACIC ANEURISM. PMID- 17863641 TI - CHRONIC CYSTIC MASTITIS OR ABNORMAL INVOLUTION OF THE BREAST. PMID- 17863642 TI - REGRESSIVE CHANGES IN THE BREAST. PMID- 17863643 TI - SPONDYLITIS DEFORMANS RELIEVED BY ALBEE OPERATION. PMID- 17863645 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held October 11, 1916. PMID- 17863644 TI - FELONS. PMID- 17863646 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, October 25, 1916. PMID- 17863647 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held October 2, 1916. PMID- 17863648 TI - FRACTURES OF THE LOWER EXTREMITY OR BASE OF THE RADIUS. PMID- 17863649 TI - TEMPORARY COLOSTOMY: A PRELIMINARY REPORT UPON A NEW TECHNIC. PMID- 17863651 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 6, 1916: Stated Meeting, Held November. PMID- 17863650 TI - FIBROMA OF THE SMALL INTESTINE RESULTING IN INTUSSUSCEPTION. PMID- 17863653 TI - GUNSHOT INJURIES OF THE PERIPHERAL NERVES AND THEIR TREATMENT. PMID- 17863652 TI - VOLKMANN'S ISCHAEMIC PARALYSIS AND CONTRACTURE. PMID- 17863654 TI - CARCINOMA OF THE BREAST. PMID- 17863656 TI - SPLENECTOMY FOR REPEATED GASTRO-INTESTINAL HEMORRHAGES. PMID- 17863655 TI - AUTOGENOUS FASCIAL RECONSTRUCTION OF THE BILE-DUCT. PMID- 17863658 TI - THE CHOICE OF OPERATIVE PROCEDURE IN CANCER OF THE RECTUM AND PELVIC COLON. PMID- 17863657 TI - ENTEROSTOMY FOR ILEUS. PMID- 17863659 TI - THE INFLUENCE OF ACIDOSIS ON SURGICAL PROCEDURES. PMID- 17863660 TI - THE CHEMOTHERAPY OF EXPERIMENTAL BACTERIAL INFECTIONS. PMID- 17863661 TI - ACUTE OSTEOMYELITIS OF THE SPINE. PMID- 17863662 TI - THE SIGNIFICANCE OF GIANT-CELLS IN BONE LESIONS. PMID- 17863664 TI - A COMPARISON OF THE PERMANENCE OF FREE TRANSPLANTS OF BONE AND CARTILAGE: AN EXPERIMENTAL STUDY. PMID- 17863663 TI - A COMPOSITE STUDY OF THE COELIAC AXIS ARTERY. PMID- 17863665 TI - STUDIES ON PAGET'S DISEASE OF THE NIPPLE AND ITS EXTRAMAMMARY OCCURRENCE: REPORTS OF EIGHTEEN CASES PERSONALLY INVESTIGATED. PMID- 17863666 TI - PAPILLOMA OF THE UMBILICUS. PMID- 17863667 TI - THE HEALING OF GASTRO-INTESTINAL ANASTOMOSES. PMID- 17863669 TI - INDICATIONS FOR THE IODOFORM WAX BONE-FILLING OF MOSETIG-MOORHOF. PMID- 17863668 TI - TRAUMATIC EXTRAPERITONEAL RUPTURE OF THE BLADDER WITH FRACTURE OF THE PELVIS. PMID- 17863670 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 4, 1916: Stated Meeting, Held December. PMID- 17863671 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 8, 1916: Stated Meeting, Held November. PMID- 17863672 TI - THE PLACE OF RADIUM IN SURGERY. PMID- 17863673 TI - INTRATHYROID INJECTIONS OF BOILING WATER IN HYPERTHYROIDISM. PMID- 17863674 TI - THE TREATMENT OF BONY DEFECTS OF THE LOWER JAW. PMID- 17863675 TI - STUDIES IN PLASTIC SURGERY OF THE FACE: I. USE OF SKIN FROM THE NECK TO REPLACE FACE DEFECTS. II. PLASTIC OPERATIONS ABOUT THE MOUTH. III. THE EPIDERMIC INLAY. PMID- 17863676 TI - TRAUMATIC ANEURISM OF THE TEMPORAL ARTERY. PMID- 17863677 TI - THE TREND OF SURGERY IN EMPYEMA OF THORAX. PMID- 17863679 TI - THE SIGNIFICANCE OF THE PATULOUS APPENDIX. PMID- 17863678 TI - THE PROGNOSTIC AND THERAPEUTIC SIGNIFICANCE OF SKELETAL METASTASES IN CARCINOMA OF THE BREAST. PMID- 17863680 TI - RENAL TUBERCULOSIS. PMID- 17863682 TI - ISOLATED SPRAIN-FRACTURE OF THE TRAPEZIUM PRODUCED BY INDIRECT VIOLENCE. PMID- 17863681 TI - REDUPLICATION OF THE URETER. PMID- 17863683 TI - ARTIFICIAL CELL PROLIFERATION WITH HORSE SERUM IN THE TREATMENT OF BURNS. PMID- 17863684 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 22, 1916: Stated Meeting, Held November. PMID- 17863685 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 13, 1916: Stated Meeting, Held December. PMID- 17863687 TI - LIGHTNING-SOME OF ITS EFFECTS. PMID- 17863686 TI - THE KERR SUTURE. PMID- 17863688 TI - SOME OBSERVATIONS IN SPINAL CORD SURGERY. PMID- 17863690 TI - ANGIONEUROTIC OEDEMA WITH VISCERAL CRISES. PMID- 17863689 TI - THE TREATMENT OF WOUND INFECTION. PMID- 17863691 TI - STAB WOUND OF THE DEEP EPIGASTRIC ARTERY: WITH COMMENTS UPON THE SURGERY OF THAT VESSEL. PMID- 17863692 TI - RETROPERITONEAL HERNIA INTO THE DUODENAL FOSSAE. PMID- 17863693 TI - ISOLATED ABSCESS OF THE LIVER COMPLICATING APPENDICITIS. PMID- 17863695 TI - THE GROSS PATHOLOGY OF MEDIAN BAR FORMATION. PMID- 17863694 TI - A NEW OPERATION FOR PROCIDENTIA UTERI. PMID- 17863696 TI - HAEMANGIOMA CAVERNOSUM OF BONE. PMID- 17863697 TI - CHRONIC MEDULLARY ABSCESS OF THE LONG BONES: ITS CLINICAL AND RONTGENOGRAPHIC FEATURES: ITS TREATMENT BY SIMPLE TREPHINING. PMID- 17863698 TI - THE TREATMENT OF FRACTURES OF THE FEMUR, ESPECIALLY IN THE OLD. PMID- 17863699 TI - FRACTURES THROUGH THE NECK OF THE ASTRAGALUS. PMID- 17863700 TI - SUPERNUMERARY BONES OF THE FOOT: AN X-RAY STUDY. PMID- 17863701 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 8, 1917: Stated Meeting, Held January. PMID- 17863702 TI - A TRIBUTE TO THE MEMORY OF PAUL M. PILCHER. PMID- 17863704 TI - THE PROBLEM OF PROSTATIC OBSTRUCTION. PMID- 17863703 TI - KIDNEY WITH DOUBLE PELVIS AND DOUBLE URETER: NEPHROLITHIASIS: PYONEPHROSIS: NEPHRECTOMY. PMID- 17863705 TI - CONGENITAL STRICTURES AND SPIRAL TWISTS OF THE URETERS. PMID- 17863706 TI - OBSERVATIONS ON ANOMALIES OF THE URINARY TRACT. PMID- 17863707 TI - NOTES ON INDICATIONS IN KIDNEY SURGERY. PMID- 17863708 TI - BILATERAL POLYCYSTIC KIDNEY: A CASE TREATED BY PUNCTURE OF THE CYSTS. PMID- 17863709 TI - A CONTRIBUTION TO ECHINOCOCCUS DISEASE OF THE KIDNEY. PMID- 17863710 TI - PRELIMINARY RENAL DRAINAGE WITH SPECIAL REFERENCE TO THE TWO-STAGE OPERATION ON THE KIDNEY. PMID- 17863711 TI - THE INFLUENCE OF THE VENOUS COLLATERAL CIRCULATION OF THE KIDNEY ON HYDRONEPHROSIS: AN EXPERIMENTAL STUDY. PMID- 17863712 TI - AN UNUSUAL CASE OF RENAL TUBERCULOSIS. PMID- 17863713 TI - BILATERAL RENAL CALCULI. PMID- 17863714 TI - EXPERIENCE WITH PAPAVERIN IN THE TREATMENT OF URETERAL CALCULUS. PMID- 17863715 TI - RECENT OBSERVATIONS IN CYSTOSCOPIC TECHNIC. PMID- 17863716 TI - THE VALUE OF BACILLUS BULGARICUS IN TREATMENT OF COCCUS INFECTIONS OF THE BLADDER. PMID- 17863717 TI - SARCOMA OF THE BLADDER IN A CHILD. PMID- 17863718 TI - THE USE OF RADIUM AND THE PUNCH OPERATION IN DESPERATE CASES OF ENLARGED PROSTATE. PMID- 17863719 TI - SIDELIGHTS ON PROSTATIC ABSCESS. PMID- 17863720 TI - NON-GONORRHOEAL AND NON-TUBERCULOUS EPIDIDYMITIS. PMID- 17863721 TI - THE SURGICAL SIGNIFICANCE OF THE ESTIMATION OF THE NON-PROTEIN NITROGENOUS CONSTITUENTS OF BLOOD: WITH ESPECIAL REFERENCE TO THE PHENOLSULPHONEPHTHALEIN TEST: A PRELIMINARY REPORT. PMID- 17863722 TI - THE RESULTS OF OPERATIONS FOR TUMORS OF THE BREAST, BENIGN AND MALIGNANT: WITH CRITIQUE ON TECHNIC. PMID- 17863724 TI - THE RESULTS OF THE TREATMENT OF LYMPHOSARCOMA BY MEANS OF X-RAYS AND OTHER METHODS. PMID- 17863723 TI - SURGICAL EXPERIENCE AND SURGICAL KNOWLEDGE: THE ANNUAL ORATION BEFORE THE PHILADELPHIA ACADEMY OF SURGERY, FEBRUARY 5, 1917. PMID- 17863725 TI - A HISTOLOGICAL STUDY OF THE CIRCULAR SUTURE OF THE BLOOD-VESSELS. PMID- 17863727 TI - CONGENITAL LIPOMATA OF THE CHEEK. PMID- 17863726 TI - STUDIES IN REGENERATION AND GROWTH OF BONE: THE DEMONSTRATION OF NEW FORMED BONE BY INTRAVITAL STAINING. PMID- 17863728 TI - A STUDY OF SECONDARY HEMORRHAGE TREATED BY LIGATION OF THE COMMON CAROTID ARTERY. PMID- 17863729 TI - A STUDY OF THE MOTOR DISTURBANCES ACCOMPANYING ULCER OF THE STOMACH OR DUODENUM AND THE CHANGES PRODUCED BY OPERATION. PMID- 17863730 TI - AN ANATOMICAL POINT WHICH FACILITATES THE LOCATION AND DELIVERY OF THE APPENDIX. PMID- 17863731 TI - CYSTIC DILATATION OF THE VERMIFORM APPENDIX. PMID- 17863732 TI - REMARKS ON TYPHOID SPINE: WITH REPORT OF A CASE. PMID- 17863733 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 5, 1917: Stated Meeting, Held February. PMID- 17863734 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 8, 1917: Stated Meeting, Held January. PMID- 17863735 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 24, 1917: Stated Meeting, Held January. PMID- 17863737 TI - CORRESPONDENCE. PMID- 17863736 TI - DEFINITION OF MAJOR AND MINOR SURGERY: A QUESTION AND AN ANSWER. PMID- 17863738 TI - GALL-BLADDER FILLED WITH CALCIUM CARBONATE PUTTY. PMID- 17863740 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 14, 1917: Stated Meeting, Held February. PMID- 17863739 TI - NOTES ON SERVICE IN THE FRENCH ARMY MEDICAL CORPS. PMID- 17863741 TI - THE X-RAY IN WAR SURGERY AND ITS RELATION TO THE REMOVAL OF FOREIGN BODIES: SPECIAL REFERENCE TO OPERATING WITH SYNCHRONOUS ASSISTANCE OF THE FLUOROSCOPE. PMID- 17863742 TI - A METHOD OF PRECISION FOR THE REMOVAL OF NEEDLES IN THE HAND: THE USE OF THE MICROPHONE. PMID- 17863743 TI - DEEP PALMAR HAND INFECTIONS: AN EXPERIMENTAL AND CLINICAL STUDY OF THE SURGICAL ANATOMY OF THESE CONDITIONS. PMID- 17863744 TI - LACERATION OF THE INFERIOR VENA CAVA: REPAIRED BY SUTURE: RECOVERY. PMID- 17863745 TI - INTRAPERICARDIAL TRAUMATIC HEMORRHAGE: TWO UNUSUAL EXPERIENCES IN HEART AND PERICARDIAL SURGERY. PMID- 17863746 TI - SUBCUTANEOUS INJURIES OF THE LIVER: A REPORT OF TEN CASES. PMID- 17863748 TI - THE VALUE OF THE X-RAY EXAMINATION IN CHOLELITHIASIS. PMID- 17863747 TI - TRANSPERITONEAL SIGMOIDOTOMY FOR THE REMOVAL OF TUMORS IN THE MUCOUS MEMBRANE. PMID- 17863749 TI - ACUTE PERFORATION OF GASTRIC AND DUODENAL ULCERS: WITH A REPORT OF 36 CASES. PMID- 17863751 TI - SOME OF THE PROBLEMS OF PLASTIC SURGERY. PMID- 17863750 TI - THE RELATION OF THE ILIOHYPOGASTRIC NERVE TO THE RADICAL CURE OF INGUINAL HERNIA: AN EXPERIMENTAL STUDY OF THE PHYSIOLOGY OF THE NERVE. PMID- 17863753 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 5, 1917: Stated Meeting, Held March. PMID- 17863752 TI - BONE AUTOGENOUS GRAFT IN THE TREATMENT OF FRACTURE OF THE GREATER TUBEROSITY OF THE HUMERUS. PMID- 17863754 TI - A CLEAN AND COMFORTABLE METHOD OF TREATING ERYSIPELAS PATIENTS. PMID- 17863755 TI - OBSERVATIONS ON THE NATURE OF POST-OPERATIVE LEUCOCYTOSIS IN THE DOG. PMID- 17863756 TI - THE VALUE OF THE LEUCOCYTE COUNT IN THE DIAGNOSIS AND PROGNOSIS OF ACUTE APPENDICITIS, AS BASED ON EXPERIENCE IN ONE HUNDRED CASES. PMID- 17863757 TI - TUMORS OF THE GASSERIAN GANGLION: WITH THE REPORT OF AN OPERATED CASE. PMID- 17863758 TI - BONE TRANSPLANTATION FROM SCAPULA FOR DEFECT IN SKULL. PMID- 17863759 TI - THE VALUE OF BONE AND CARTILAGE TRANSPLANTS IN RHINOLOGICAL SURGERY. PMID- 17863760 TI - FACTORS BEARING ON THE MORTALITY IN OPERATIONS FOR BILIARY OBSTRUCTION BY CALCULUS. PMID- 17863762 TI - POST-OPERATIVE PARALYTIC ILEUS. PMID- 17863761 TI - THE ETIOLOGICAL RELATIONS OF THE SEQUELAE TO GASTRO-ENTEROSTOMY: TOGETHER WITH THE DESCRIPTION OF A SIMPLE OPERATIVE TECHNIC. PMID- 17863763 TI - FRACTURES OF THE DIFFERENT BONES OCCURRING IN THE GOLD MINING INDUSTRY: END RESULTS AND ECONOMIC STUDY OF 311 CONSECUTIVE CASES. PMID- 17863764 TI - ON THE NATURE OF NEUROPATHIC AFFECTIONS OF THE JOINTS. PMID- 17863765 TI - AN ANATOMIC SUBSTITUTE FOR THE FEMALE BREAST. PMID- 17863766 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held February 28, 1917. PMID- 17863767 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting held March 14, 1917. PMID- 17863768 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting held March 28, 1917. PMID- 17863770 TI - THE CARREL METHOD OF TREATING WOUNDS. PMID- 17863769 TI - CONSERVATISM IN SURGERY: THE PRESIDENTIAL ADDRESS DELIVERED BEFORE THE AMERICAN SURGICAL ASSOCIATION, BOSTON, MASS., MAY 31, 1917. PMID- 17863771 TI - OBSERVATIONS UPON SHOCK, WITH PARTICULAR REFERENCE TO THE CONDITION AS SEEN IN WAR SURGERY. PMID- 17863772 TI - INJECTION OF THE GASSERIAN GANGLION FOR NEURALGIA OF THE FIFTH CRANIAL NERVE. PMID- 17863773 TI - EMPYEMA OF THE THORAX: REPORT OF ONE HUNDRED CASES TREATED IN THE SURGICAL SERVICE OF THE WRITER, AT MT. SINAI HOSPITAL. PMID- 17863774 TI - DILATATION OF THE HEART, WITH ACUTE MYOCARDITIS, FOLLOWING ABDOMINAL OPERATIONS. PMID- 17863775 TI - EPIGASTRIC HERNIA WITHOUT PALPABLE SWELLING. PMID- 17863776 TI - PARAFFINE HERNIA: HERNIA COMPLICATED BY PARAFFINE INJECTIONS. PMID- 17863777 TI - HYPERNEPHROMA IN THE FOLDS OF THE FALCIFORM LIGAMENT OF THE LIVER. PMID- 17863778 TI - CHOLECYSTECTOMY: UNDER WHAT CIRCUMSTANCE SHOULD IT BE DONE? PMID- 17863779 TI - ACUTE SUPPURATIVE CELLULITIS OF THE STOMACH: WITH REPORT OF THREE CASES. PMID- 17863781 TI - A SIMPLE METHOD OF RESECTING THE TRANSVERSE COLON: WITH PRESERVATION OF THE OMENTUM: LIKEWISE FOR THE SUSPENSION OF A PROLAPSED COLON. PMID- 17863780 TI - A METHOD OF GASTRO-ENTEROSTOMY. PMID- 17863782 TI - CARCINOMA OF THE SPLENIC FLEXURE OF THE COLON. PMID- 17863784 TI - PROSTATECTOMY. PMID- 17863783 TI - INFECTIONS IN PROSTATE CASES. PMID- 17863786 TI - THE HANDLING OF EARLY AND DOUBTFUL CASES OF CANCER. PMID- 17863785 TI - SOME FURTHER DATA ON ARTIFICIAL IMPACTION OF THE HIP. PMID- 17863787 TI - A TECHNIC FOR THE RADICAL CAUTERY OPERATION IN BREAST CANCER. PMID- 17863788 TI - REGIONAL ANAESTHESIA IN EXTRAPLEURAL THORACOPLASTY AND SOME INTRATHORACIC OPERATIONS. PMID- 17863789 TI - THE ADVANTAGE OF CHOLECYSTECTOMY IN THE AVOIDANCE OF ADHESIONS IN GALL-BLADDER SURGERY. PMID- 17863790 TI - POSTURE IN CASES OF ABDOMINAL DRAINAGE. PMID- 17863791 TI - OPERATIVE TREATMENT OF HOUR-GLASS STOMACH: WITH REPORT OF A CASE TREATED BY DOUBLE POSTERIOR GASTRO-ENTEROSTOMY. PMID- 17863792 TI - THE EXTENT OF TISSUE TO BE EXCISED FOR A RADICAL REMOVAL OF CARCINOMA OF THE STOMACH. PMID- 17863793 TI - HYPERPLASTIC PYLORIC STENOSIS. PMID- 17863794 TI - GIANT DUODENUM: WITH REPORT OF A CASE IN A CHILD. PMID- 17863795 TI - MEGACOLON: MEGASIGMOID: HIRSCHSPRUNG'S DISEASE. PMID- 17863796 TI - THE SAFE ELIMINATION OF THE COLON FOR THE RELIEF OF UNCONTROLLABLE INTESTINAL STASIS. PMID- 17863797 TI - IDIOPATHIC CHOLEDOCHUS CYST: WITH REPORT OF A CASE CURED BY CHOLEDOCHODUODENOSTOMY. PMID- 17863798 TI - RELATIVE INDICATIONS FOR CHOLECYSTECTOMY AND CHOLECYSTOTOMY. PMID- 17863799 TI - TORSION AND INFLAMMATION OF THE APPENDICES EPIPLOICAE. PMID- 17863800 TI - ULTIMATE RESULTS FOLLOWING NEPHROPEXY IN CASES OF SYMPTOMATIC NEPHROPTOSIS. PMID- 17863801 TI - CONGENITAL ELEVATION OF THE SCAPULA: SPRENGEL'S DEFORMITY. PMID- 17863802 TI - A NEW METHOD OF EXCISING THE HEAD OF THE HUMERUS. PMID- 17863803 TI - FUNGOUS DISEASES OF THE FOOT, OR MADURA FOOT, IN AMERICA. PMID- 17863805 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held April 11, 1917. PMID- 17863804 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held April 2, 1917. PMID- 17863806 TI - THE TREATMENT OF STAPHYLOCOCCUS SEPTICAEMIA BY TRANSFUSION OF IMMUNE BLOOD. PMID- 17863807 TI - PERSISTENCE OF BACTERIA WITHIN SEQUESTRA. PMID- 17863808 TI - DIABETES INSIPIDUS AS A SEQUEL TO A GUNSHOT WOUND OF THE HEAD. PMID- 17863809 TI - TRAUMATIC BRACHIAL PARALYSIS WITH FLAIL SHOULDER JOINT: WITH A REPORT OF THREE OLD AND ELEVEN NEW CASES. PMID- 17863811 TI - GALL-STONES IN INFANCY AND CHILDHOOD. PMID- 17863810 TI - MYXOFIBROMATA OF THE ABDOMINAL WALL. PMID- 17863813 TI - ENTEROSTOMY AND THE USE OF THE OMENTUM IN THE PREVENTION AND HEALING OF FISTULA. PMID- 17863812 TI - NOTES ON FOUR KINDS OF APPENDICITIS. PMID- 17863814 TI - HISTOPATHOLOGY OF CARCINOMA OF THE TESTICLE. PMID- 17863815 TI - THE UNIVERSITY HOSPITAL SHOULDER SPLINT. PMID- 17863816 TI - AN EVALUATION OF ASEPSIS AND ANTISEPSIS. PMID- 17863817 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held April 25, 1917. PMID- 17863818 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held May 9, 1917. PMID- 17863819 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held May 7, 1917. PMID- 17863820 TI - TRAUMATIC ANEURISM OF THE TEMPORAL ARTERY. PMID- 17863821 TI - STUDIES IN BONE REGENERATION: AN EXPERIMENTAL STUDY OF BONE TRANSPLANTATION BY MEANS OF A VITAL STAIN. PMID- 17863822 TI - THE COMPLETE MASTOID OPERATION: ITS RELATION TO THE MODERN HEALING OF MASTOID WOUNDS. PMID- 17863823 TI - DISLOCATION OF THE CERVICAL VERTEBRAE: REPORT OF TWO INSTANCES COMPLETELY REDUCED MANUALLY WITHOUT ANAESTHESIA. PMID- 17863824 TI - TUBERCULOSIS OF THE APPENDIX. PMID- 17863825 TI - OBSTRUCTION OF THE URETER. PMID- 17863826 TI - ON GASTRIC AND DUODENAL ULCERS FROM A SURGICAL POINT OF VIEW. PMID- 17863827 TI - ANNULAR SEGMENTAL GASTRECTOMY. PMID- 17863828 TI - STRICTURE OF THE GALL-BLADDER: DUME-BELL GALL-BLADDER. PMID- 17863829 TI - TUMORS OF THE BLADDER: WITH REPORT OF 26 CASES. PMID- 17863830 TI - INGUINAL HERNIA IN THE MALE: WITH REGARD TO POST-OPERATIVE SEQUELAE. PMID- 17863831 TI - FRACTURES OF THE OS CALCIS: A STUDY OF SEVENTY-TWO CASES. PMID- 17863832 TI - AN ANATOMICAL AND EXPERIMENTAL STUDY OF SACRAL ANAESTHESIA. PMID- 17863833 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held October 10, 1917. PMID- 17863834 TI - FURTHER OBSERVATIONS ON THE RESULTS OF BLOOD TRANSFUSION IN WAR SURGERY: WITH SPECIAL REFERENCE TO THE RESULTS IN PRIMARY HEMORRHAGE. PMID- 17863835 TI - THE TREATMENT OF GONORRHOEAL EPIDIDYMITIS, COMPLICATED BY PERI-EPIDIDYMITIS. PMID- 17863837 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 1, 1917: Stated Meeting, Held October. PMID- 17863836 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 24, 1917: Stated Meeting, Held October. PMID- 17863838 TI - THE USE OF DICHLORAMINE-T IN THE TREATMENT OF INFECTIONS AND INFECTED WOUNDS. PMID- 17863840 TI - PULSE RATE AND BLOOD-PRESSURE OBSERVATIONS AS AN AID IN THE TREATMENT OF HEAD TRAUMAS. PMID- 17863839 TI - BIRTH INJURIES OF THE SHOULDER. PMID- 17863841 TI - FRACTURES OF THE SPINE WITH CORD AND ROOT SYMPTOMS: SOME INDICATIONS FOR AND CONTRA-INDICATIONS TO EARLY OPERATIVE INTERFERENCE. PMID- 17863842 TI - THE SO-CALLED "MIXED TUMORS" OF THE SALIVARY GLANDS: WITH A POSSIBLE EXPLANATION OF THE MORPHOLOGICAL BEHAVIOR OF THE TUMOR CELLS. PMID- 17863843 TI - HYGROMA COLLI. PMID- 17863844 TI - PULMONARY TERATOMA: REPORT OF A CASE WITH REMARKS ON OVIGENOUS TUMORS. PMID- 17863846 TI - TECHNIC OF OPERATION FOR REPAIR OF THE ILEOCAECAL VALVE: WITH SUMMARY OF THE RESULTS IN A SERIES OF TWENTY-SIX CASES. PMID- 17863845 TI - GASTRODUODENOSTOMY: ITS INDICATIONS AND TECHNIC. PMID- 17863847 TI - DUMB-BELL STONE IN DIVERTICULUM OF URINARY BLADDER. PMID- 17863848 TI - NOTES ON THE RECOGNITION OF CERTAIN LESIONS OF THE MALE BLADDER. PMID- 17863849 TI - A STUDY OF ANTE-OPERATIVE AND POST-OPERATIVE BLOOD COUNTS IN NON-INFECTIVE SURGICAL CONDITIONS. PMID- 17863850 TI - ELECTRIC BURN CAUSING NECROSIS OF THE SKULL. PMID- 17863851 TI - DEEP PALMAR HAND INFECTIONS: A CLINICAL STUDY OF THE DIAGNOSIS AND TREATMENT OF THESE CONDITIONS. PMID- 17863852 TI - BONE TRANSPLANTATION IN THE SURGICAL TREATMENT OF PARALYTIC FEET. PMID- 17863853 TI - NOTE ON TUBERCULOSIS OF THE SPINE. PMID- 17863855 TI - APPARATUS FOR THE TREATMENT OF COMPOUND FRACTURES OF THE FOREARM. PMID- 17863854 TI - THE GENERAL PRINCIPLES OF TREATMENT OF WOUNDS OF THE KNEE-JOINT FROM PROJECTILES IN WARFARE. PMID- 17863857 TI - ABDOMINAL WOUND TECHNIC. PMID- 17863856 TI - A NEW INCISION FOR EXPOSURE OF THE LOWER ABDOMEN AND PELVIS. PMID- 17863858 TI - RESECTION OF THE LARGE BOWEL AT THE RECTOSIGMOIDAL JUNCTION. PMID- 17863859 TI - LEFT PARADUODENAL HERNIA. PMID- 17863860 TI - THE DISTRIBUTION OF FAT IN THE APPENDIX AND ITS RELATION TO INFLAMMATION. PMID- 17863862 TI - INTESTINAL OBSTRUCTION: AN EXPERIMENTAL STUDY. PMID- 17863861 TI - SPONTANEOUS PAN-HYSTERECTOMY AFTER ABDOMINAL CONTUSION. PMID- 17863863 TI - THE ETIOLOGICAL RELATIONSHIP OF BENIGN ULCER TO CARCINOMA OF THE STOMACH. PMID- 17863865 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held November 14, 1917. PMID- 17863866 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, Held December 12, 1917. PMID- 17863864 TI - AN IMPROVED MILITARY AMBULANCE. PMID- 17863867 TI - PAROVARIAN CYST IN A YOUNG GIRL. PMID- 17863868 TI - THE HYPOCHONDRIAC TYMPANY SYMPTOM OF PERFORATED GASTRODUODENAL ULCERS. PMID- 17863870 TI - THE EFFECT OF TRAUMA UPON THE LARYNGEAL NERVES: AN EXPERIMENTAL STUDY. PMID- 17863869 TI - SUTURE OF WOUND IN FEMORAL ARTERY. PMID- 17863871 TI - PNEUMOCOCCUS PERITONITIS. PMID- 17863872 TI - OBSTRUCTIVE (MALIGNANT) JAUNDICE: OPERATIVE RELIEF BY CHOLECYSTOGASTROSTOMY, ETC. PMID- 17863873 TI - ACUTE AND SUBACUTE PANCREATITIS: REPORT OF SEVEN CASES. PMID- 17863874 TI - ACCESSORY PANCREAS WITH INTUSSUSCEPTION. PMID- 17863875 TI - SPLENECTOMY IN SPLENOMEGALIES. PMID- 17863877 TI - ON OSSEOUS CYSTS AND SO-CALLED GIANT-CELL SARCOMA. PMID- 17863876 TI - INFLAMMATORY TUMORS OF THE ABDOMEN. PMID- 17863878 TI - REGENERATION OF BONE. PMID- 17863879 TI - TRAUMATIC LUXATION OF THE SACRO-ILIAC SYMPHYSIS WITHOUT FRACTURE OF THE PELVIS. PMID- 17863880 TI - FIBROCYSTIC AND CYSTIC LESIONS IN BONE. PMID- 17863881 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held January 9, 1918. PMID- 17863882 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held November 5, 1917. PMID- 17863883 TI - BILATERAL DISLOCATION OF THE SIXTH CERVICAL VERTEBRA FORWARDS. PMID- 17863884 TI - THE CHLORINE ANTISEPTICS IN CIVIL HOSPITAL USE. PMID- 17863885 TI - BISMUTH PASTE IN WAR SURGERY: ITS USE IN COMBINATION WITH THE SKIN SLIDING OPERATIONS FOR CHRONIC SUPPURATIONS AND LUNG ABSCESS. PMID- 17863886 TI - INJURIES TO THE MALAR BONE AND ZYGOMA. PMID- 17863887 TI - KINEPLASTIC AMPUTATIONS. PMID- 17863888 TI - SPLINT FOR THE TREATMENT AND TRANSPORT OF CASES OF FRACTURE OF THE FEMUR. PMID- 17863889 TI - HOSPITAL BED DESIGNED FOR MILITARY HOSPITALS: WITH A SPECIAL MODEL FOR CIVIL HOSPITALS. PMID- 17863890 TI - THE TYING OF A SURGICAL KNOT. PMID- 17863892 TI - CONSERVATION OF THE THYROID IN HYPERTHYROIDISM. PMID- 17863891 TI - THE BIOLOGICAL AND CLINICAL EVIDENCE OF THE THERAPEUTIC VALUE OF RADIUM AND RONTGEN RAYS IN CANCER. PMID- 17863893 TI - MADDERIZED BONE AS A MATERIAL FOR BONE-GRAFTS. PMID- 17863895 TI - NOTE ON ISOLATED ABSCESSES OF LONG BONES. PMID- 17863894 TI - THE USE OF SMALL BONE TRANSPLANTS IN BRIDGING A BONE DEFECT. PMID- 17863896 TI - NITROUS OXIDE, OXYGEN, ANAESTHOL SEQUENCE IN ORAL SURGERY. PMID- 17863898 TI - ON THE USE OF OLIVE OIL IN BLOOD-VESSEL SUTURING. PMID- 17863897 TI - RECTUS MUSCLE TRANSPOSITION IN CERTAIN CASES OF INGUINAL HERNIA. PMID- 17863899 TI - NOTE ON SAPHENOUS VARIX SIMULATING A FEMORAL HERNIA. PMID- 17863900 TI - THE RECURRENCE OF SYMPTOMS FOLLOWING OPERATIONS ON THE BILIARY TRACT. PMID- 17863901 TI - ACUTE DILATATION OF THE STOMACH FOLLOWING PROSTATECTOMY. PMID- 17863902 TI - THE MECHANISM OF OBSTRUCTION IN PROSTATIC ADENOMA. PMID- 17863903 TI - TERATOMA OF THE SACRUM: GLIOMA OF THE UPPER ABDOMINAL CAVITY. PMID- 17863904 TI - REPAIR OF COMPLETE RECTOVAGINAL LACERATIONS. PMID- 17863905 TI - CANCER OF RECTUM. PMID- 17863906 TI - SKIN ASEPSIS IN SURGERY. PMID- 17863907 TI - OPERATIVE TREATMENT OF FRACTURE OF THE SPINE UNCOMPLICATED BY CORD INJURY. PMID- 17863909 TI - CONTRACTURE OF THE BLADDER (HYPERTONIA VESICAE) DUE TO SPINAL INJURY. PMID- 17863908 TI - SURGERY OF SPASTIC PARALYSIS. PMID- 17863910 TI - LOOSE CARTILAGE IN THE TEMPOROMAXILLARY JOINT: SUBLUXATION OF THE INFERIOR MAXILLA. PMID- 17863911 TI - THE PREVENTION OF PERMANENT BRONCHIAL FISTULA FOLLOWING LUNG RESECTION: A CLINICAL NOTE. PMID- 17863912 TI - THE EFFECT OF SPLENECTOMY ON THE NORMAL INDIVIDUAL AND IN CERTAIN PATHOLOGICAL CONDITIONS. PMID- 17863913 TI - THE VALUE OF PYLORIC EXCLUSION IN THE TREATMENT OF PYLORIC AND DUODENAL ULCERS. PMID- 17863914 TI - IMMEDIATE JEJUNAL FEEDING AFTER GASTRO-ENTEROSTOMY. PMID- 17863915 TI - DEVELOPMENTAL RECONSTRUCTION OF THE COLON: ANIMAL RESEARCHES AND CLINICAL REPORT OF TWENTY-NINE HUMAN CASES. PMID- 17863916 TI - OMPHALOMESENTERIC DUCT: INTESTINAL OBSTRUCTION. PMID- 17863917 TI - CLOSURE OF THE ABDOMINAL INCISION. PMID- 17863918 TI - A COMPOSITE STUDY OF THE HYPOGASTRIC ARTERY AND ITS BRANCHES. PMID- 17863920 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held December 3, 1917. PMID- 17863919 TI - FRACTURE OF GREAT TOE SESAMOID BONES. PMID- 17863921 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, Held January 23, 1918. PMID- 17863922 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, Held February 13, 1918. PMID- 17863923 TI - TORSION AND STRANGULATION OF A PYOSALPINX. PMID- 17863924 TI - ON TUMORS OF THE SALIVARY GLANDS. PMID- 17863925 TI - CONGENITAL VARIATIONS IN THE PERITONEAL RELATIONS OF THE ASCENDING COLON, CAECUM, APPENDIX AND TERMINAL ILEUM. PMID- 17863926 TI - THE MULTIPLE MYELOMATA AND THEIR ABILITY TO METASTASIZE. PMID- 17863927 TI - THE PROGNOSIS AND TREATMENT OF EMPYEMA: WITH RESPECT TO THE SHAPE OF THE CAVITY AND THE RELATION OF THE LUNG TO THE CHEST WALLS. PMID- 17863928 TI - TREATMENT OF PENETRATING GUNSHOT WOUNDS OF THE CHEST WITH HEMORRHAGE INTO THE PLEURA. PMID- 17863929 TI - THE RELATION OF GASTRIC ULCER TO CANCER. PMID- 17863930 TI - CAUTERY EXCISION OF GASTRIC ULCER: FURTHER OBSERVATIONS ON THE VALUE OF THE METHOD. PMID- 17863931 TI - RELIEF OF UMBILICAL HERNIA BY THE CONDEMINRANSOHOFF TECHNIC. PMID- 17863933 TI - MECHANICAL DERANGEMENT OF THE KNEE-JOINT. PMID- 17863932 TI - CONGENITAL IDIOPATHIC DILATATION OF THE COLON OR HIRSCHSPRUNG'S DISEASE. PMID- 17863934 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held February 27, 1918. PMID- 17863935 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held March 13, 1918. PMID- 17863936 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held March 27, 1918. PMID- 17863938 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 8, 1918: Stated Meeting, Held May. PMID- 17863937 TI - THE USE OF FASCIAL TRANSPLANTS IN WAR SURGERY. PMID- 17863939 TI - Acker, Single Abscess of Liver. PMID- 17863940 TI - LAMINECTOMY AND REGIONAL ANAESTHESIA. PMID- 17863941 TI - THE ADVISABILITY OF TOTALLY EXCISING BOTH PECTORAL MUSCLES IN THE RADICAL OPERATION FOR CANCER OF THE BREAST. PMID- 17863943 TI - OBLITERATION OF THE COMMON BILE-DUCT FOLLOWING OPERATION: CURED BY AN HEPATICODUODENOSTOMY. PMID- 17863942 TI - THE INTERRELATION OF STASIS, PTOSIS AND INERTIA OF THE INTESTINAL TRACT. PMID- 17863944 TI - CLONORCHIS SINENSIS INFECTION OF THE GALL-BLADDER AND BILIARY PASSAGES. PMID- 17863946 TI - VENTRICULOGRAPHY FOLLOWING THE INJECTION OF AIR INTO THE CEREBRAL VENTRICLES. PMID- 17863945 TI - A CONTRIBUTION TO THE KNOWLEDGE OF FUSED KIDNEYS. PMID- 17863947 TI - SURGICAL IMPORTANCE OF SUPERNUMERARY ARTERIES TO THE KIDNEY. PMID- 17863949 TI - FIBRIN PAPER AS AN HAEMOSTATIC AGENT. PMID- 17863948 TI - PLASTIC (RECONSTRUCTIVE) SURGERY OF THE HAND AND THE FOREARM. PMID- 17863950 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 7, 1918: Stated Meeting, Held February. PMID- 17863951 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 7, 1918: Stated Meeting, Held March. PMID- 17863953 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 24, 1918: Stated Meeting, Held April. PMID- 17863952 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 10, 1918: Stated Meeting, Held April. PMID- 17863954 TI - PRESIDENTIAL ADDRESS BEFORE THE AMERICAN SURGICAL ASSOCIATION. PMID- 17863955 TI - THE VALUE OF THE TRANSFUSION OF BLOOD IN THE TREATMENT OF THE WOUNDED IN WAR. PMID- 17863956 TI - THE ROLE OF THE EVACUATION HOSPITAL IN THE CARE OF THE WOUNDED. PMID- 17863957 TI - THE RELATION OF ORTHOPAEDIC TO GENERAL SURGERY. PMID- 17863958 TI - CLINICAL OBSERVATIONS CONCERNING MALIGNANT TUMORS OF THE JAWS. PMID- 17863959 TI - RECURRENT DISLOCATION OF THE LOWER JAW. PMID- 17863960 TI - TWO CASES OF ENLARGED THYROID PRODUCING SUFFOCATION BY DISPLACEMENT BENEATH THE STERNUM. PMID- 17863961 TI - AN APPLICATION TO EMPYEMA OF THE PRINCIPLES UNDERLYING THE USE OF ANTISEPTICS. PMID- 17863962 TI - HEMORRHAGE FROM AN ANEURISM OF THE INTERNAL CAROTID ARTERY, FOLLOWING SEPTIC SORE THROAT. PMID- 17863963 TI - POST-OPERATIVE THORACIC DRAINAGE. PMID- 17863964 TI - THE TREATMENT OF DISEASES OF THE COSTAL CARTILAGES. PMID- 17863965 TI - THE SURGICAL TREATMENT OF THE CIRRHOSES OF THE LIVER AND THEIR COMPLICATIONS. PMID- 17863966 TI - CHOLECYSTITIS. PMID- 17863967 TI - A METHOD OF PERMANENT GASTROSTOMY. PMID- 17863968 TI - SPASTIC ILEUS (SPASMODIC INTESTINAL OBSTRUCTION). PMID- 17863969 TI - RIGHT COLECTOMY. PMID- 17863970 TI - FISTULA OF THE COLON. PMID- 17863971 TI - OBSERVATIONS ON THE TREATMENT OF DIRECT INGUINAL HERNIA IN ADULTS. PMID- 17863973 TI - THE USE OF THE PEDUNCULATED FLAP IN RECONSTRUCTIVE SURGERY. PMID- 17863972 TI - LIGATION OF THE ABDOMINAL AORTA: LIGATION OF THE FIRST PORTION OF THE LEFT SUBCLAVIAN. PMID- 17863975 TI - AMPUTATIONS OF THE LEG. PMID- 17863974 TI - HEREDITARY OSTEOPSATHYROSIS. PMID- 17863976 TI - RESULTS OBTAINABLE IN THE TREATMENT OF FRACTURES: REPORT OF THE COMMITTEE ON FRACTURES OF THE AMERICAN SURGICAL ASSOCIATION PRESENTED JUNE 6, 1918. PMID- 17863977 TI - PRELIMINARY REPORT OF A METHOD FOR ESTIMATING IN VIVO THE GERMICIDAL ACTIVITY OF ANTISEPTICS. PMID- 17863978 TI - TREATMENT OF GUNSHOT FRACTURES OF THE MANDIBLE. PMID- 17863979 TI - OPERATIVE TREATMENT OF HERNIA: A CONSIDERATION OF 8589 CASES OF HERNIA TREATED BY RADICAL OPERATION FROM 1891 TO 1918, WITH SPECIAL REFERENCE TO METHODS OF OPERATING AND END RESULTS. PMID- 17863980 TI - LIPOMA OF THE FUNICULUS SPERMATICUS. PMID- 17863981 TI - FECAL FISTULA FOLLOWING STRANGULATED HERNIA, WITH REPORT OF FIVE CASES OPERATED UPON. PMID- 17863982 TI - THE TRAUMATIC ABDOMEN. PMID- 17863983 TI - ACUTE PANCREATITIS. PMID- 17863984 TI - THE INCIDENCE OF CALCULI IN THE GALL-BLADDER AS MET WITH IN 1600 NECROPSIES. PMID- 17863986 TI - DIVERTICULA OF THE BLADDER. PMID- 17863985 TI - KIDNEY-URETER ABNORMALITIES. PMID- 17863987 TI - A NOTE ON THE TREATMENT OF WOUNDS OF THE GENITAL ORGANS IN WARFARE. PMID- 17863988 TI - ANATOMICAL METHODS OF APPROACH IN OPERATIONS ON THE LONG BONES OF THE EXTREMITIES. PMID- 17863989 TI - LENGTHENING OF THE TENDO ACHILLIS IN THE TREATMENT OF COMPLICATED POTT'S FRACTURE. PMID- 17863990 TI - RECEIVING AND OPERATING PAVILIONS FOR A MODERN BASE HOSPITAL. PMID- 17863992 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held April 4, 1918. PMID- 17863991 TI - THE TREATMENT OF MALIGNANT PERITONITIS OF OVARIAN ORIGIN. PMID- 17863994 TI - SIMPLIFYING CEREBRAL LOCALIZATION. PMID- 17863993 TI - SKIN ASEPSIS IN SURGERY. PMID- 17863995 TI - THE TREATMENT OF TUMORS OF THE SUPERIOR MAXILLA. PMID- 17863996 TI - THE OPERATIVE TREATMENT OF TRIFACIAL NEURALGIA. PMID- 17863997 TI - A NOTE ON THE SURGICAL TREATMENT OF CERTAIN DISEASES BY SPLENECTOMY. PMID- 17863999 TI - HYPERNEPHROMA OF THE FALCIFORM LIGAMENT OF THE LIVER. PMID- 17863998 TI - SURGICAL ASPECTS OF RIGHT SUBPHRENIC ABSCESS. PMID- 17864000 TI - THE LOW LATERAL INCISION AND A METHOD OF NERVE BLOCK FOR APPENDECTOMY. PMID- 17864002 TI - THE HUMAN SEMINAL VESICLES AT BIRTH-WITH OBSERVATIONS ON THEIR FETAL DEVELOPMENT. PMID- 17864001 TI - SURGICAL PATHOLOGY OF THE HUMAN PROSTATE GLAND. PMID- 17864003 TI - TRANSVERSE ECTOPY OF THE TESTIS WITH MASCULINE UTERUS. PMID- 17864004 TI - GIANT-CELL GROWTH OF BONE AND TENDON SHEATH: GIANT-CELL SARCOMA, BENIGN MYELOMA, ETC. PMID- 17864006 TI - SURGICAL CLOSURE OF WOUNDS. PMID- 17864005 TI - INTESTINAL OBSTRUCTION PRODUCED BY THE EVAGINATION OF ILEUM INTO THE URINARY BLADDER. PMID- 17864008 TI - THE AMERICAN RED CROSS SPLINTS. PMID- 17864007 TI - THE PHYSICAL FACTORS INFLUENCING INFECTION. PMID- 17864009 TI - UTILIZATION OF PLATINUM IN UNUSED INSTRUMENTS. PMID- 17864010 TI - THE VALUE AND LIMITATIONS OF LABORATORY STUDIES OF ACIDOSIS IN SURGERY. PMID- 17864011 TI - THE HOSPITALS OF THE AMERICAN EXPEDITIONARY FORCE. PMID- 17864012 TI - QUINO-FORMOL SOLUTION IN WAR SURGERY: A PRELIMINARY REPORT. PMID- 17864013 TI - HISTORY ANALYSIS APPLIED TO SURGICAL DISEASES OF THE BILIARY TRACT AND PANCREAS. PMID- 17864014 TI - A CONTRIBUTION TO THE STUDY OF MYOSITIS OSSIFICANS PROGRESSIVA. PMID- 17864015 TI - A RADIOLUCENT SEMILUNAR SHADOW OCCURRING AS A CONSTANT FACTOR IN CERTAIN CASES OF SEVERE INTERMITTENT HEADACHE: PRELIMINARY REPORT. PMID- 17864016 TI - IMPORTANT POINTS RELATING TO THE SURGICAL TREATMENT OF PROSTATIC HYPERTROPHY. PMID- 17864017 TI - THE AMBULANCE AIRSHIP: A FACTOR MAKING FOR IMPROVED ARTICULATION BETWEEN THE MEDICAL DEPARTMENT AND THE FLYING OFFICE. PMID- 17864019 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held January 7, 1918. PMID- 17864018 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, Held October 9, 1918. PMID- 17864020 TI - LUMBAR PUNCTURE AS APPLIED TO CRANIOCEREBRAL SURGERY. PMID- 17864021 TI - PRESENT-DAY VIEWS OF THE PATHOLOGY OF SYPHILIS. PMID- 17864022 TI - THE SURGERY OF GUNSHOT INJURIES OF THE THORAX. PMID- 17864023 TI - SKIN LESIONS PRODUCED BY MUSTARD GAS. PMID- 17864024 TI - IODINE AS A SKIN DISINFECTANT PREVIOUS TO INTRA-ABDOMINAL WORK. PMID- 17864025 TI - EXTIRPATION OF THE CHOROID PLEXUS OF THE LATERAL VENTRICLES IN COMMUNICATING HYDROCEPHALUS. PMID- 17864026 TI - RIB CARTILAGE TRANSPLANT FOR SADDLE-BACK NOSE. PMID- 17864027 TI - ARTERIOMESENTERIC ILEUS OF DUODENOJEJUNAL FLEXURE. PMID- 17864029 TI - A CONTRIBUTION TO THE STUDY OF MYOSITIS OSSIFICANS PROGRESSIVA. PMID- 17864028 TI - PRIMARY RETROGRADE INTUSSUSCEPTION OF THE SIGMOID ASSOCIATED WITH TUMOR. PMID- 17864030 TI - THE DANGERS OF UTERINE CURETTAGE. PMID- 17864031 TI - SURGICAL TECHNIC IN ORTHOPAEDIC SURGERY. PMID- 17864032 TI - WAR SURGERY OF THE ABDOMEN. PMID- 17864033 TI - THE LATE RESULTS OF GUNSHOT WOUNDS OF THE CHEST. PMID- 17864034 TI - THE EARLY TREATMENT OF SEPTIC PLEURAL EFFUSIONS COMPLICATING PENETRATING WOUNDS OF THE CHEST. PMID- 17864036 TI - A NOTE ON THE TREATMENT OF COMPOUND FRACTURES OF THE SKULL WITH OPEN DURA. PMID- 17864035 TI - TOTAL PLEURECTOMY FOR PACHYPLEURITIS. PMID- 17864038 TI - OPERATIVE TREATMENT OF HARELIP AND CLEFT PALATE. PMID- 17864037 TI - Treatment of Wounds of the Foot. PMID- 17864039 TI - NON-PARASITIC CYSTS OF THE SPLEEN. PMID- 17864040 TI - VARIABILITY OF THE PATHOLOGY AND SYMPTOMS OF CHRONIC INTESTINAL OBSTRUCTION. PMID- 17864041 TI - RESECTION OF THE CAECUM AND ASCENDING COLON. PMID- 17864043 TI - A SOURCE OF ERROR IN INTERPRETATION OF RONTGENOGRAMS OF THE SKULL. PMID- 17864044 TI - LEGG'S DISEASE: ARTHRITIS DEFORMANS JUVENILIS: OSTEOCHONDRITIS DEFORMANS JUVENILIS: "PERTHES'S" DISEASE. PMID- 17864042 TI - TORSION OF APPENDICES EPIPLOICAE. PMID- 17864045 TI - NOTES ON THE USE OF RUBBER GLOVES IN SURGICAL OPERATIONS. PMID- 17864046 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 13, 1918: Stated Meeting, Held November. PMID- 17864047 TI - Janssen on Cranioplasty: Its Indications and Its Technic. PMID- 17864048 TI - Harde on the Frequency of Tetanus Bacilli and of Other Anaerobic Microorganisms upon the Surface of Fragments of Projectiles Which Have Been Extracted from Wounds. PMID- 17864049 TI - Treatment of Chronic Osteomyelitis of Traumatic Origin. PMID- 17864051 TI - Final Results of the Treatment of Fracture of the Shaft of the Femur. PMID- 17864050 TI - THE SURGICAL TREATMENT OF CANCER OF THE SUPERIOR MAXILLA. PMID- 17864053 TI - Depage on the Opening Up of Gunshot Wounds. PMID- 17864052 TI - Late Extraction of Missiles Imbedded in the Lung. PMID- 17864054 TI - STUDIES IN BONE TRANSPLANTATION; A STUDY OF A METHOD OF INCREASING THE OSTEOGENETIC POWER OF A FREE BONE TRANSPLANT. PMID- 17864055 TI - THE ADVANTAGES OF PICRIC ACID OVER TINCTURE OF IODINE FOR DISINFECTION OF SKIN. PMID- 17864056 TI - POST-OPERATIVE PAROTITIS. PMID- 17864057 TI - THE FREQUENCY OF "STRAWBERRY" GALL-BLADDERS. PMID- 17864059 TI - ABDOMINAL DRAINAGE. PMID- 17864058 TI - THE FREQUENCY OF ADENOMYOMA OF THE UTERUS. PMID- 17864060 TI - FRACTURES OF THE UPPER END OF THE HUMERUS. PMID- 17864062 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting, held December 12, 1918. PMID- 17864061 TI - THE USE AND[ill]VALUE OF THE LANE PLATE. PMID- 17864064 TI - GORDON HOLMES ON THE TREATMENT OF SECONDARY AND LATE COMPLICATIONS OF BRAIN WOUNDS. PMID- 17864063 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated meeting, held December 11, 1918. PMID- 17864065 TI - GOSSET ON FUNCTIONAL RESULTS OF OPERATIONS UPON PERIPHERAL NERVES. PMID- 17864066 TI - JOYCE ON PERIPHERAL NERVE INJURIES. PMID- 17864067 TI - WILLEMS ON MOBILIZATION IN THE TREATMENT OF INTRA-ARTICULAR FRACTURES. PMID- 17864068 TI - THE FORMATION OF BONE. PMID- 17864069 TI - THE REPAIR OF CRANIAL DEFECTS. PMID- 17864070 TI - ON SOME LESIONS OBSERVED IN OPERATIONS FOR OLD INJURIES TO THE SPINAL CORD, WITH REMARKS AS TO TREATMENT. PMID- 17864071 TI - ON THE DIAGNOSIS AND THERAPY OF BONE TYPHOID. PMID- 17864072 TI - DIAPHRAGMATIC HERNIA: ITS UNSUSPECTED FREQUENCY: ITS DIAGNOSIS: TECHNIC FOR RADICAL CURE. PMID- 17864073 TI - GAS AND THE MOTILITY OF THE SURGICAL STOMACH. PMID- 17864074 TI - FATTY HERNIAS: WITH A REPORT OF A CASE OF STRANGULATED FATTY HERNIA ENVELOPING AN EMPTY FEMORAL SAC. PMID- 17864075 TI - ANURIA AFTER UNILATERAL NEPHRECTOMY. PMID- 17864076 TI - ADHESIVE PLASTER METHOD FOR THE RAPID REGENERATION OF SKIN OVER GRANULATING WOUNDS. PMID- 17864077 TI - EXPERIMENTAL RESEARCH ON THE EFFECT OF INTRAVENOUS INJECTION OF GUM SALT SOLUTIONS. PMID- 17864078 TI - THE TREATMENT OF BURNS: AN EXPERIENCE IN THIRTY-ONE CASES DUE TO FOREST FIRES. PMID- 17864080 TI - SUPPURATING CYST OF THE URACHUS, WITH CONCRETION. PMID- 17864079 TI - THE INITIAL TREATMENT OF WAR WOUNDS INVOLVING THE KNEE-JOINT. PMID- 17864081 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held January 8, 1919. PMID- 17864082 TI - BONE TUMORS. CENTRAL (MEDULLARY) GIANT-CELL TUMOR (SARCOMA) OF LOWER END OF ULNA, WITH EVIDENCE THAT COMPLETE DESTRUCTION OF THE BONY SHELL OR PERFORATION OF THE BONY SHELL IS NOT A SIGN OF INCREASED MALIGNANCY. PMID- 17864083 TI - FURTHER STUDIES IN OSTEOGENESIS. PMID- 17864084 TI - EFFACEMENT OF CAVITIES IN THE TREATMENT OF FRACTURES. PMID- 17864085 TI - SYNTHETIC TRANSPLANTATION OF TISSUES TO FORM NEW FINGER: WITH RESTORED FUNCTION OF HAND. PMID- 17864086 TI - A NOTE ON EXPERIMENTAL CRANIOPLASTY. PMID- 17864088 TI - EXPOSURE IN GALL-BLADDER SURGERY. PMID- 17864087 TI - HYPERTONIC GUM ACACIA AND GLUCOSE IN THE TREATMENT OF SECONDARY TRAUMATIC SHOCK. PMID- 17864089 TI - LONG RESECTIONS OF THE INTESTINE. PMID- 17864090 TI - LOTHEISEN'S OPERATION FOR FEMORAL HERNIA. PMID- 17864091 TI - TRANSPLANTATION OF THE VERMIFORM APPENDIX INTO THE FEMALE BLADDER TO SUPPLY AN ABSENT URETHRA. PMID- 17864092 TI - TREATMENT OF STREPTOCOCCUS SEPTICAEMIA COMPLICATED BY WOUND DIPHTHERIA, MAKING USE OF TRANSFUSION OF BLOOD IMMUNE TO THE STREPTOCOCCUS. PMID- 17864093 TI - DOUBLE-EYED ANEURISM NEEDLE. PMID- 17864094 TI - FREE TRANSPLANTATION OF TENDONS. PMID- 17864095 TI - COMPLETE TORSION OF GREAT OMENTUM. PMID- 17864096 TI - THE INFLUENCE OF THE WAR UPON THE DEVELOPMENT OF SURGERY. PMID- 17864097 TI - FRACTURE OF THE FEMUR: A CRITICAL ANALYSIS OF 131 CASES OF FRACTURE OF THE FEMUR, TREATED AT THE AMERICAN RED CROSS HOSPITAL, NO. 2, PARIS. PMID- 17864098 TI - THE DISINFECTION OF VITALIZED TISSUES AND THE HEALING OF WOUNDS WITH CHINOSOL AND SALT. PMID- 17864099 TI - A SERIES OF WAR WOUNDS TREATED WITH DICHLORAMINE-T. PMID- 17864100 TI - REMARKS ON THE ETIOLOGY, INDICATIONS FOR TREATMENT, BEHAVIOR, AND POST-OPERATIVE COURSE OF EMPYEMA THORACIS. PMID- 17864101 TI - ACUTE DILATATION OF THE STOMACH. PMID- 17864102 TI - PYLORIC STENOSIS IN INFANCY. PMID- 17864104 TI - PRIMARY LYMPHOSARCOMA OF THE INTESTINES: WITH REPORT OF TWO CASES. PMID- 17864103 TI - CHOLECYSTITIS FOLLOWING TYPHOID FEVER IN CHILDHOOD. PMID- 17864105 TI - "THE GUILLOTINE AMPUTATION". PMID- 17864106 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held February 12, 1919. PMID- 17864107 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting held February 13, 1919. PMID- 17864109 TI - GENERAL CONSIDERATIONS AS TO THE TREATMENT OF WAR WOUNDS. PMID- 17864108 TI - THE INFLUENCE OF WAR SURGERY UPON CIVIL PRACTICE: PRESIDENT'S ADDRESS BEFORE THE AMERICAN SURGICAL ASSOCIATION, JUNE 16, 1919. PMID- 17864110 TI - THE TREATMENT OF BURNS: AS EXEMPLIFIED IN THIRTY-TWO CASES. PMID- 17864112 TI - FIBROMA OF THE INTERNAL OBLIQUE AND TRANSVERSALIS MUSCLES. PMID- 17864111 TI - MYXOMA. PMID- 17864114 TI - A CASE IN WHICH FOR OVER THIRTY-FIVE YEARS A WOMAN DEFECATED AND URINATED, AND FOR ELEVEN YEARS MENSTRUATED BY THE RECTUM. PMID- 17864113 TI - UMBILICAL TERATOMA: A REPORT OF A CASE CONTAINING PANCREAS AND INTESTINE. PMID- 17864115 TI - VAGINAL HERNIA. PMID- 17864116 TI - WHY IS END-TO-END INTESTINAL ANASTOMOSIS UNSAFE?: A CLINICAL AND EXPERIMENTAL STUDY OF TECHNIC, INDICATIONS AND CONTRAINDICATIONS FOR END-TO-END ANASTOMOSIS OF THE SMALL INTESTINE AND THE COLON. PMID- 17864117 TI - DEFORMITY OF THE SCAPULAE ASSOCIATED WITH A CERVICAL RIB AND A SPINA BIFIDA. PMID- 17864118 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held March 12, 1919. PMID- 17864119 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting held April 9, 1919. PMID- 17864120 TI - CRANIOPLASTY. THE VALUE OF A GRAFT OF BONE, CARTILAGE OR FASCIA IN THE CLOSURE OF CRANIAL DEFECTS CAUSED BY WOUNDS IN WAR: A STUDY OF THE RESULTS OBTAINED IN A SERIES OF FORTY-TWO OPERATIONS. PMID- 17864121 TI - NEW INSTRUMENTS FOR PROCURING AND PREPARING AUTOGENOUS BONE BOLTS AND KEYS AND SPECIAL METHODS OF THEIR APPLICATION IN SHAFT FRACTURES. PMID- 17864122 TI - NOTE ON THE USE OF AUTOGENOUS BONE GRAFTS, SECURED AND APPLIED AFTER THE METHOD OF BELL. PMID- 17864123 TI - THE TREATMENT OF ACUTE GASTROMESENTERIC ILEUS. PMID- 17864125 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting held March 13, 1919. PMID- 17864124 TI - THE NO-FLAP OR GUILLOTINE AMPUTATION: AN UNFORTUNATE RESURRECTION. PMID- 17864126 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting held April 7, 1919. PMID- 17864127 TI - A CLAMP FOR OSTEOPLASTIC CRANIOTOMY. PMID- 17864128 TI - THE RESULTS OF SPLENECTOMY IN THE ANAEMIAS. PMID- 17864130 TI - THE DELAYED OR LATE EXTRACTION OF INTRATHORACIC PROJECTILES BY THE METHOD OF PETIT DE LA VILLEON. PMID- 17864129 TI - THE TREATMENT OF GUNSHOT WOUNDS OF THE CHEST. PMID- 17864131 TI - THORACIC FISTULA AND CHRONIC EMPYEMA: A NON-DEFORMING OPERATION FOR ITS CURE. PMID- 17864132 TI - EMPYEMA. PMID- 17864133 TI - THE TREATMENT OF EMPYEMA. PMID- 17864134 TI - FOREIGN BODIES IN THE STOMACH. PMID- 17864135 TI - INGUINAL HERNIA: AN OPERATIVE METHOD BY WHICH CLOSE TO 100 PER CENT. CURES HAVE BEEN OBTAINED. PMID- 17864136 TI - THE TRANSPLANTATION OF THE RECTUS MUSCLE OR ITS SHEATH FOR THE CURE OF INGUINAL HERNIA WHEN THE CONJOINED TENDON IS OBLITERATED. THE TRANSPLANTATION OF THE SARTORIUS MUSCLE FOR THE CURE OF RECURRENT HERNIA WHEN POUPART'S LIGAMENT HAS BEEN DESTROYED. PMID- 17864137 TI - STRANGULATED AND IRREDUCIBLE HERNIAE. PMID- 17864138 TI - ROENTGEN EXAMINATION OF THE ABDOMINAL ORGANS FOLLOWING OXYGEN INFLATION OF THE PERITONEAL CAVITY. PMID- 17864139 TI - EXPERIMENTAL HYDROCEPHALUS. PMID- 17864140 TI - CONCUSSION OF THE BRAIN: A STUDY IN DIAGNOSIS. PMID- 17864141 TI - TRAUMATIC FACIAL DIPLEGIA. PMID- 17864142 TI - A CLINICAL STUDY OF NERVE ANASTOMOSIS. PMID- 17864143 TI - RHINOPHYMA. PMID- 17864144 TI - TRANSTHORACIC LAPAROTOMY. PMID- 17864145 TI - DIAPHRAGMATIC HERNIA. PMID- 17864147 TI - POST-INFLUENZAL ABSCESS OF THE SHEATH OF THE RECTUS MUSCLE. PMID- 17864146 TI - THE ASSOCIATION OF MALIGNANT MYOMATA WITH MECKEL'S DIVERTICULUM. PMID- 17864148 TI - INDICATIONS FOR OPERATION IN URETERAL CALCULI. PMID- 17864149 TI - SOME DIFFICULTIES IN THE DIAGNOSIS AND TREATMENT OF UNILATERAL RENAL TUBERCULOSIS. PMID- 17864150 TI - FIBROMA OF THE TESTICLE. PMID- 17864151 TI - A NEW OPERATING COMPOSITE CYSTO-URETHROSCOPE. PMID- 17864152 TI - DUPUYTREN'S CONTRACTURE, WITH A DESCRIPTION OF A METHOD OF OPERATION. PMID- 17864153 TI - GUNSHOT INJURY OF THE MUSCULOSPIRAL NERVE. PMID- 17864154 TI - THE APPLICATION OF EXTENSION TO OVERLAPPING FRACTURES, ESPECIALLY OF THE TIBIA, BY MEANS OF BONE SCREWS AND A TURNBUCKLE, WITHOUT OPEN OPERATION. PMID- 17864155 TI - CANCER OF THE STOMACH AND ITS SURGICAL TREATMENT. PMID- 17864156 TI - THE METHOD OF RECORDING SURGICAL OPERATIONS AT THE FRONT. PMID- 17864157 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting held May 5, 1919. PMID- 17864158 TI - REPORT OF 82 CASES OF KNEE-JOINT WAR INJURIES. PMID- 17864160 TI - OPEN AMPUTATION THROUGH THE KNEE-JOINT. PMID- 17864159 TI - TREATMENT OF RECENT WOUNDS OF THE KNEE-JOINT. PMID- 17864161 TI - GUNSHOT INJURIES OF THE KNEE-JOINT IN A BASE HOSPITAL. PMID- 17864162 TI - FRACTURE OF THE ACETABULUM WITH INTRAPELVIC DISPLACEMENT OF THE FEMORAL HEAD. PMID- 17864163 TI - REPAIR BY AUTOGENOUS BONE GRAFTING IN FRACTURES OF LONG BONES. PMID- 17864165 TI - PNEUMOPERITONEUM: A METHOD OF DETECTING INTESTINAL PERFORATION-AN AID IN ABDOMINAL DIAGNOSIS. PMID- 17864164 TI - THE CORRECTION OF DEFORMITY IN FRACTURES WITH A NEW CONCEPTION OF THE MECHANISM OF FRACTURES OF THE UPPER EXTREMITY. PMID- 17864166 TI - CHRONIC INFLAMMATORY TUMOR OF OMENTUM. PMID- 17864167 TI - THE MOST IMPORTANT FACTOR IN THE TREATMENT OF WAR WOUNDS AND THE MOST IMPORTANT FACTOR IN CIVILIAN SURGERY-THE GOOD SURGEON. PMID- 17864168 TI - THE PROBLEM OF THE "SLIGHTLY WOUNDED" IN MILITARY AND CIVILIAN PRACTICE. PMID- 17864169 TI - WHAT WOULD BE THE BENEFIT TO THE CIVILIAN SURGEON IN THE EXPERIENCE GAINED BY OUR MILITARY SURGEONS IN THE RECENT WORLD WAR? PMID- 17864171 TI - FRACTURE OF THE SKULL WITH SPECIAL REFERENCE TO ITS NEUROLOGICAL MANIFESTATIONS. PMID- 17864170 TI - RONTGENOGRAPHY OF THE BRAIN AFTER THE INJECTION OF AIR INTO THE SPINAL CANAL. PMID- 17864173 TI - FRACTURES OF THE LOWER THIRD OF THE FEMUR. PMID- 17864172 TI - GUNSHOT FRACTURES OF THE HUMERUS TREATED BY SUSPENSION AND TRACTION. PMID- 17864174 TI - THE CONTRIBUTION OF THE WAR TO THE SURGERY OF THE KNEE-JOINT. PMID- 17864175 TI - POCKETING OPERATIONS AND OTHER SKIN AND FAT TRANSFERS. PMID- 17864176 TI - THE BARREL-STAVE SPLINT IN FRACTURE OF THE CLAVICLE. PMID- 17864177 TI - PHASES OF WAR SURGERY: BONE TRANSPLANTS FROM THE TIBIA TO THE LOWER JAW FOR LOSS OF SUBSTANCE. PMID- 17864178 TI - FOREIGN BODIES ARRESTED IN THE DUODENUM. PMID- 17864179 TI - "ENURESIS" OF ADULTS; HYPERTONIC BLADDER. PMID- 17864180 TI - THE ORGANIZATION AND OPERATION OF AN EVACUATION HOSPITAL. PMID- 17864181 TI - THE THREE-TABLE MILITARY OPERATING ROOM A PLAN APPLICABLE TO CIVIL HOSPITALS. PMID- 17864182 TI - SIMPLE BANDAGE FOR FRACTURE OF THE CLAVICLE. PMID- 17864183 TI - THE USE OF VEINS AS A REINFORCEMENT AND SUPPORT OF NERVE SUTURE. PMID- 17864185 TI - THE IMPORTANCE OF THE SPLEEN IN RESISTANCE TO INFECTION. PMID- 17864186 TI - LIFE EXPECTANCY OF PATIENTS FOLLOWING OPERATIONS FOR GASTRIC AND DUODENAL ULCER. PMID- 17864184 TI - A METHOD FOR THE PREVENTION OF HAEMATOMA FORMATION AFTER OPERATIONS FOR UNDESCENDED TESTIS. PMID- 17864187 TI - OPERATIVE TREATMENT OF PEPTIC ULCER; REMOVAL OF ULCER WITH GASTRO-ENTEROSTOMY, OR GASTRO-ENTEROSTOMY ALONE. PMID- 17864188 TI - CHOLEDOCHO-ENTEROSTOMY AND POSTOPERATIVE DILATION OF THE BILE-DUCTS: AN EXPERIMENTAL STUDY. PMID- 17864189 TI - THE CONDITION OF THE APPENDIX IN FIVE HUNDRED LAPAROTOMIES ON PATIENTS REPRESENTING NO SYMPTOMS OF APPENDICITIS. PMID- 17864190 TI - LUNG ABSCESS. PMID- 17864191 TI - TREATMENT OF CHRONIC EMPYEMA: RESULTS OBTAINED AT U. S. GENERAL HOSPITAL NO. 26, FORT DES MOINES, IOWA. PMID- 17864192 TI - TREATMENT OF CHRONIC EMPYEMA. PMID- 17864193 TI - THE PATHOGENESIS AND TREATMENT OF LYMPHOSARCOMA AND HODGKIN'S GRANULOMA. PMID- 17864194 TI - TUBERCULOSIS OF SUBMAXILLARY AND CERVICAL GLANDS IN THE ELDERLY. PMID- 17864195 TI - BENIGN XANTHIC EXTRAPERIOSTEAL TUMOR OF THE EXTREMITIES CONTAINING FOREIGN BODY GIANT CELLS. PMID- 17864196 TI - GLIOMA OF THE BUTTOCK. PMID- 17864197 TI - EXPERIMENTAL RESECTION OF THE DOG'S KNEE JOINT: SECOND STUDY. PMID- 17864198 TI - FRACTURES OF THE NECK OF THE FEMUR: ANALYSIS OF 116 CASES. PMID- 17864199 TI - FRACTURE OF THE FEMUR: THE APPLICATION OF WAR LESSONS TO CIVIL PRACTICE. PMID- 17864200 TI - GENITO-URINARY SURGERY IN AN ARMY GENERAL HOSPITAL. PMID- 17864202 TI - FURTHER OBSERVATIONS ON THE CONSERVATIVE TREATMENT OF SARCOMA OF THE LONG BONES. PMID- 17864201 TI - SALVAGE OF THE HAND BY TIMELY REPARATIVE SURGERY. PMID- 17864203 TI - AN ANALYSIS OF THE RESULTS OF SIX YEARS' FOLLOW-UP SYSTEM IN A HOSPITAL SURGICAL SERVICE. PMID- 17864205 TI - POST-OPERATIVE SUPPURATIVE PAROTITIS. PMID- 17864204 TI - WAR SURGERY UNDER FRONT-LINE CONDITIONS: REPORT OF THE WORK OF CASUAL SURGICAL TEAM NO. 506 (ORIGINALLY NO. 6) FROM JUNE 18, 1918, TO AUGUST 8, 1918. PMID- 17864206 TI - DRAINAGE IN APPENDICITIS: A REVIEW OF CASES OF ACUTE APPENDICITIS REQUIRING DRAINAGE AT THE PRESBYTERIAN HOSPITAL, NEW YORK, N. Y., 1915-1918. PMID- 17864207 TI - ANKYLOSING OPERATIONS ON THE TUBERCULOUS SPINE: LABORATORY EXAMINATION OF A SPECIMEN. PMID- 17864208 TI - AN EXPERIMENTAL STUDY OF BURIED BONE. PMID- 17864209 TI - THE SELF-RETAINING SLIDE BONE GRAFT. PMID- 17864210 TI - THE USE OF METALLIC FIXATURES IN SECURING BONE FRAGMENTS: PRESSURE ANALYSIS AND A NEW METAL BONE BOLT. PMID- 17864211 TI - LEFT BRANCHIAL CYST OPENING ON THE RIGHT SIDE. PMID- 17864213 TI - THE PREPARATION OF THE SKIN FOR OPERATION WITH SOLUTION OF RUBBER AND ETHER INSTEAD OF TINCTURE OF IODINE. PMID- 17864212 TI - SURGICAL PROBLEMS IN THE RECONSTRUCTION OF PERIPHERAL NERVE INJURIES. PMID- 17864214 TI - LYMPHOSARCOMA OF THE MESENTERY. PMID- 17864215 TI - SPLENECTOMY UNDER LOCAL ANAESTHESIA. PMID- 17864216 TI - DISLOCATION OF THE FIVE METATARSAL BONES DOWNWARD AND OUTWARD FROM THE TARSUS WITHOUT FRACTURE. PMID- 17864217 TI - RECURRENT NEPHROLITHIASIS. PMID- 17864218 TI - HOUR-GLASS BLADDER: REMARKS ON THE RESECTION OF THE BASE OF THE BLADDER FOR TRANSVERSE SEPTA. PMID- 17864219 TI - ELEPHANTIASIS AND THE KONDOLEON OPERATION. PMID- 17864220 TI - STUDIES IN BONE GROWTH: TRIPLE CALCIUM PHOSPHATE AS A STIMULUS TO OSTEOGENESIS. PMID- 17864222 TI - THE TREATMENT OF BONE CAVITIES. PMID- 17864221 TI - A STUDY OF THE CAUSE OF DELAYED UNION AND NON-UNION IN FRACTURES OF THE LONG BONES. PMID- 17864223 TI - THE TREATMENT OF CENTRAL LUXATION OF THE FEMUR. PMID- 17864224 TI - GUNSHOT FRACTURES OF THE TIBIA AND FIBULA: OBSERVATIONS ON THE PATHOLOGY AND TREATMENT. PMID- 17864225 TI - THE RAPID CLOSURE OF SURGICAL WOUNDS, ESPECIALLY OF LAPAROTOMIES. PMID- 17864226 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 8, 1919: Stated Meeting, Held October. PMID- 17864227 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 16, 1919: Stated Meeting, Held October. PMID- 17864228 TI - OXYCEPHALY: REPORT OF TWO CASES. PMID- 17864229 TI - THE SURGICAL TREATMENT OF CYSTS OF THE THYROGLOSSAL TRACT. PMID- 17864230 TI - STONE IN THE KIDNEY. PMID- 17864231 TI - THE RESULTS OF OPERATIONS FOR THE REMOVAL OF STONES FROM THE URETER. PMID- 17864233 TI - "NO SURGICAL APPENDICITIS WITHOUT ORGANIC STRICTURE". PMID- 17864232 TI - TUBERCULOSIS OF THE APPENDIX. PMID- 17864235 TI - ANATOMICAL CONSIDERATIONS IN THE RECTAL PROLAPSE OF INFANTS. PMID- 17864234 TI - THE ADVANTAGES OF THE MIKULICZ TWO-STAGE OPERATION OF PARTIAL COLECTOMY. PMID- 17864236 TI - SARCOMA OF THE PROSTATE. PMID- 17864237 TI - ABSCESS OF THE PROSTATE. PMID- 17864238 TI - CERVICAL EROSIONS. PMID- 17864239 TI - TREATMENT OF NON-UNION IN COMPOUND FRACTURES. PMID- 17864241 TI - SUTURE OF WAR WOUNDS. PMID- 17864240 TI - DISLOCATION OF THE TARSAL SCAPHOID: DOUBLE FRACTURE OF THE ISCHIATIC TUBEROSITIES. PMID- 17864243 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated meeting, held November 26, 1919. PMID- 17864242 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting, held November 12, 1919. PMID- 17864244 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting held November 3, 1919. PMID- 17864245 TI - TRAVELS OF A WIRE IN THE ABDOMEN. PMID- 17864246 TI - DOUBLE INTERVAL ECTOPIC WITH RETENTION OF SIX-MONTHS FOETUS. PMID- 17864247 TI - POSSIBLE ADVANCES IN CIVIL MEDICINE SUGGESTED BY EXPERIENCES IN TREATING WAR INJURIES OF THE CHEST. PMID- 17864248 TI - WAR WOUNDS OF THE CHEST. PMID- 17864249 TI - GUNSHOT WOUNDS OF THE CHEST. PMID- 17864251 TI - DIAPHRAGMATIC HERNIA. PMID- 17864250 TI - OPERATIVE RESULTS IN TWO HUNDRED BREAST TUMORS. PMID- 17864252 TI - CONGENITAL DIAPHRAGMATIC HERNIA: WITH REPORT OF A CASE. PMID- 17864253 TI - SURGERY OF THE DUCTUS COMMUNIS CHOLEDOCHUS. PMID- 17864254 TI - A PERMANENT COLOSTOMY OR ENTEROSTOMY WHICH MAY BE CLOSED BY AN EXTRAPERITONEAL OPERATION. PMID- 17864255 TI - GASTRO-ENTEROSTOMY STILL THE TREATMENT FOR CHRONIC GASTRIC AND DUODENAL ULCER. PMID- 17864256 TI - TECHNIC OF APPENDECTOMY: DESCRIPTION OF A RATIONAL, SAFE AND EASY TECHNIC OF THE OPERATION FOR ACUTE AND INTERVAL APPENDICITIS. PMID- 17864257 TI - FRACTURES OF THE PELVIS: WITH A REPORT OF TWENTY-FIVE CASES. PMID- 17864258 TI - USE OF FREE SKIN GRAFTS TO REPLACE LOSS OF MUCOUS MEMBRANE OF MOUTH AND NOSE. PMID- 17864259 TI - OPERATIVE TREATMENT OF UNUNITED FRACTURES OF THE MANDIBLE. PMID- 17864260 TI - BONE INLAYS AND BONE PLATINGS. PMID- 17864261 TI - A CONSIDERATION OF THE SURGICAL HAZARDS IN DIABETIC PATIENTS. PMID- 17864262 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting held December 10, 1919. PMID- 17864263 TI - PHILADELPHIA ACADEMY OF SURGERY Stated Meeting held December 1, 1919. PMID- 17864264 TI - CORRESPONDENCE. PMID- 17864265 TI - SURGICAL ENGLISH. PMID- 17864266 TI - SOME EXPERIENCES AND OBSERVATIONS IN THE TREATMENT OF ARTERIOVENOUS ANEURISMS BY THE INTRASACCULAR METHOD OF SUTURE (ENDO-ANEURISMORRHAPHY) WITH SPECIAL REFERENCE TO THE TRANSVENOUS ROUTE. PMID- 17864267 TI - STUDY OF ARTERIOVENOUS FISTULA WITH AN ANALYSIS OF 447 CASES. PMID- 17864268 TI - THE TREATMENT OF MALIGNANT TUMORS OF THE THYMUS GLAND BY RADIUM. PMID- 17864270 TI - CIRCUMSCRIBED PAN-MURAL ULCERATIVE CYSTITIS: ELUSIVE ULCER (HUNNER). PMID- 17864269 TI - MALIGNANT DISEASE OF THE LUNGS, ITS EARLY RECOGNITION AND PROGRESSIVE DEVELOPMENT, AS STUDIED BY THE RONTGEN RAYS, WITH REMARKS ON TREATMENT. PMID- 17864272 TI - PROJECTILE FRACTURES OF LONG BONES: A COMPARATIVE MECHANICAL STUDY. PMID- 17864271 TI - HYPOSPADIAS, WITH PARTICULAR REFERENCE TO THE OPERATION OF BUCKNALL. PMID- 17864273 TI - A FORM OF SPLINT AVAILABLE IN THE TREATMENT OF FRACTURES OF THE NECK OF THE FEMUR. PMID- 17864275 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting held January 5, 1920. PMID- 17864274 TI - ANHYDROUS COCAINE SPINAL ANAESTHESIA. PMID- 17864276 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting held January 14, 1920. PMID- 17864277 TI - FINGER EXPLORATION OF GUNSHOT WOUNDS OF THE BRAIN. PMID- 17864278 TI - CRANIO-CEREBRAL WOUNDS DUE TO PROJECTILES. PMID- 17864279 TI - FOREIGN BODIES OF DENTAL ORIGIN IN A BRONCHUS PULMONARY COMPLICATION. PMID- 17864280 TI - MULTIPLE HEMORRHAGIC FOCI IN BONE: CHRONIC HEMORRHAGIC OSTEOMYELITIS. PMID- 17864281 TI - COMPRESSION FRACTURES OF THE LOWER END OF THE RADIUS. PMID- 17864282 TI - PSEUDOMYXOMA PERITONEI: WITH REPORT OF SIX CASES. PMID- 17864284 TI - HYPERPLASTIC TUBERCULOSIS OF THE INTESTINES. PMID- 17864283 TI - SARCOMA OF THE STOMACH: WITH REPORT OF THREE CASES. PMID- 17864286 TI - INJURIES OF THE SEMILUNAR CARTILAGES OF THE KNEE-JOINT. PMID- 17864285 TI - THE RESULTS OBTAINED IN THE TREATMENT OF CHRONIC ARTHRITIS BY THE REMOVAL OF A DISTANT FOCUS OF INFECTION. PMID- 17864287 TI - REPORT ON THE USE OF HYCLORITE AND A MODIFIED DAKIN'S SOLUTION AS A SUBSTITUTE FOR THE ORIGINAL DAKIN'S SOLUTION. PMID- 17864288 TI - A GASTRO-ENTEROSTOMY CLAMP SIMPLIFIED AND IMPROVED. PMID- 17864289 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Regular Meeting, Held February 25, 1920. PMID- 17864290 TI - FRACTURE OF THE OS NAVICULARE PEDIS. PMID- 17864291 TI - DUODENAL HEMORRHAGE DUE TO SUTURE. PMID- 17864292 TI - THE RELATIVE VALUES OF RADIUM AND SURGERY IN THE TREATMENT OF TUMORS OF THE PELVIC ORGANS. PMID- 17864293 TI - AMPUTATION OF THE LEG. PMID- 17864294 TI - ACCIDENTS AND PRECAUTIONS IN LIGATION OF THE COMMON CAROTID ARTERY: REPORT OF A FATAL HEMIPLEGIA. PMID- 17864295 TI - REPORT OF THE CONDITION OF A CASE OF COMPLETE DIVISION OF THE SPINAL CORD BY GUNSHOT WOUND NINETEEN YEARS AFTER THE INJURY. PMID- 17864296 TI - FISH-SCALE GALL-BLADDER. PMID- 17864297 TI - THE RELATION OF VARIATIONS IN THE RENAL VESSELS TO PYELOTOMY AND NEPHRECTOMY. PMID- 17864298 TI - MODIFIED TECHNIC FOR THE RADICAL CURE OF INGUINAL HERNIA IN THE MALE. PMID- 17864299 TI - THE UTILIZATION OF THE EXTERNAL OBLIQUE APONEUROSIS IN INGUINAL HERNIA WITH MUSCLE DEFICIENCY. PMID- 17864300 TI - MULTIPLE FIBROIDS IN THE MALE PELVIS. PMID- 17864301 TI - INTESTINAL OBSTRUCTION DUE TO THE ASCARIS LUMBRICOIDS. PMID- 17864302 TI - THE PORTABLE SUSPENSION FRAME EMPLOYED IN THE TREATMENT OF THE WOUNDED DURING THE EUROPEAN WAR: ERRONEOUSLY CALLED THE BALKAN FRAME. PMID- 17864304 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting held March 1, 1920. PMID- 17864303 TI - THE CHLORINE ANTISEPTICS. PMID- 17864305 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Regular Meeting, Held at the New York Academy of Medicine, February 11, 1920. PMID- 17864306 TI - BILATERAL CONGENITAL DISLOCATION OF THE HEAD OF THE RADIUS ANTERIORLY. PMID- 17864307 TI - THE DUTIES AND RESPONSIBILITIES OF THE CIVIL SURGEON WHEN CALLED TO ACTIVE SERVICE. PMID- 17864308 TI - THE CALLOUSED ULCER OF THE POSTERIOR WALL OF THE STOMACH. PMID- 17864309 TI - FAILURE OF PRIMARY ROTATION OF THE INTESTINE (LEFT-SIDED COLON) IN RELATION TO INTESTINAL OBSTRUCTION. PMID- 17864310 TI - OBSERVATIONS ON EMPYEMA. PMID- 17864311 TI - MESENTERIC THROMBOSIS: WITH A REPORT OF 6 CASES. PMID- 17864312 TI - OPERATION FOR EMPYEMA IN YOUNG ADULTS. PMID- 17864313 TI - THE ETIOLOGY OF CHRONIC EMPYEMA. PMID- 17864315 TI - EMPYEMA: A SYLLABUS OF OPERATIVE TREATMENT. PMID- 17864314 TI - OBSERVATIONS ON THE TREATMENT OF CHRONIC EMPYEMA. PMID- 17864317 TI - GOITRE: A CLINICAL STUDY OF ONE HUNDRED AND THIRTY-NINE CASES. PMID- 17864316 TI - FATAL POST-OPERATIVE PULMONARY THROMBOSIS. PMID- 17864318 TI - ADENOMA WITH HYPERTHYROIDISM. PMID- 17864319 TI - SPECIAL CONSIDERATION OF TOXIC ADENOMA IN RELATION TO EXOPHTHALMIC GOITRE. PMID- 17864320 TI - RESULTS OF OPERATIONS FOR ADENOMA WITH HYPERTHYROIDISM AND EXOPHTHALMIC GOITRE. PMID- 17864321 TI - TOXIC GOITRE. PMID- 17864322 TI - THE MANAGEMENT OF TOXIC GOITRE FROM THE SURGICAL POINT OF VIEW. PMID- 17864323 TI - A "TOURNIQUET OPERATION" IN TOXIC AND OTHER GOITRES. PMID- 17864325 TI - LATE RESULTS AFTER THE RADICAL OPERATION FOR CANCER OF THE BREAST. PMID- 17864324 TI - THE RELATIONSHIP BETWEEN RANULA AND BRANCHIO-GENETIC CYSTS. PMID- 17864326 TI - THE REQUIREMENTS OF TECHNIC IN OPERATIONS FOR CANCER OF THE BREAST. PMID- 17864327 TI - TRAUMATIC FAT NECROSIS OF THE FEMALE BREAST AND ITS DIFFERENTIATION FROM CARCINOMA. PMID- 17864328 TI - HYPERPLASTIC TUBERCULOSIS OF THE SMALL INTESTINE. PMID- 17864329 TI - ACUTE INTESTINAL OBSTRUCTION. THE CAUSE OF THE CONTINUED HIGH MORTALITY; HOW THIS MAY BE REDUCED. PMID- 17864330 TI - CAUSES OF DEATH BY ACUTE APPENDICITIS AFTER OPERATION: Study of Two Hundred and Fifty-five Cases. PMID- 17864331 TI - OPERATION FOR CURE OF LARGE VENTRAL HERNIA. PMID- 17864332 TI - CANCER OF THE OVARY INVADING THE SIGMOID FLEXURE. PMID- 17864333 TI - THE RADICAL TREATMENT OF X-RAY BURNS. PMID- 17864334 TI - ETIOLOGY, PATHOLOGY AND CLINICAL FEATURES OF BENIGN EXOSTOSES. PMID- 17864336 TI - SOME OF THE THINGS THAT SURGEONS AS A PROFESSION STAND FOR. PMID- 17864335 TI - SARCOMA OF THE CLAVICLE-END-RESULTS FOLLOWING TOTAL EXCISION. PMID- 17864337 TI - THE TREATMENT OF CHRONIC EMPYEMA. PMID- 17864338 TI - THE TREATMENT OF CHRONIC EMPYEMA. PMID- 17864339 TI - THE MORELLI METHOD OF ASPIRATION DRAINAGE FOR ACUTE EMPYEMA. PMID- 17864340 TI - ABSCESS OF THE LUNG. PMID- 17864341 TI - THE TREATMENT OF BRONCHIAL FISTULAE. PMID- 17864342 TI - PENETRATING WAR[ill]WOUNDS OF THE CHEST: A CLINICAL STUDY OF ONE HUNDRED AND SIXTY CASES. PMID- 17864343 TI - THORACO-ABDOMINAL INJURIES: SOME TECHNICAL PROCEDURES DEVELOPED BY THE WAR. PMID- 17864344 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting held March 10, 1920. PMID- 17864345 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting held March 24, 1920. PMID- 17864347 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY JOINT MEETING HELD WITH THE NEW YORK SURGICAL SOCIETY February 2, 1920. PMID- 17864346 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting held April 14, 1920. PMID- 17864348 TI - THE INDICATIONS FOR ACTIVE IMMEDIATE MOBILIZATION IN THE TREATMENT OF JOINT INJURIES. PMID- 17864350 TI - THE ROLE OF CANCELLOUS TISSUE IN HEALING BONE. PMID- 17864349 TI - ON FRACTURES OF THE FOREARM IN THE REGION OF THE WRIST: WITH SPECIAL REFERENCE TO THE DIFFERENT TYPES OF RADIUS FRACTURE, THEIR MANNER OF ORIGIN AND MECHANISM. PMID- 17864351 TI - THE RECOGNITION OF DEAD BONE BASED ON PATHOLOGICAL AND X-RAY STUDIES. PMID- 17864352 TI - ON THE DIAGNOSIS AND THERAPY OF BONE TYPHOID. PMID- 17864353 TI - SURGICAL ASPECTS OF THE CHARCOT JOINT AND OTHER SYPHILITIC BONE AND JOINT LESIONS. PMID- 17864354 TI - FORWARD DISLOCATION OF THE ASTRAGALUS AND WITH IT THE FOOT. PMID- 17864355 TI - ADVENTITIOUS LIGAMENTS SIMULATING CERVICAL RIBS. PMID- 17864356 TI - SPERMATOCELE. PMID- 17864357 TI - A CONSIDERATION OF THE VARICOCELE OPERATION AND THE AVOIDANCE OF POST-OPERATIVE INDURATION. PMID- 17864358 TI - CUTTING THE BONE FLAP IN CRANIAL SURGERY. PMID- 17864359 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting held April 5, 1920. PMID- 17864360 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting held April 27, 1920. PMID- 17864361 TI - HYPOPHYSEAL DUCT TUMORS: A REPORT OF THREE CASES AND A FOURTH CASE OF CYST OF RATHKE'S POUCH. PMID- 17864362 TI - THE TREATMENT OF CRANIOCEREBRAL WOUNDS AND ITS RESULTS. PMID- 17864363 TI - A NEW APPLIANCE TO SECURE PROPER POSITION AND STEADINESS OF THE HEAD DURING BRAIN OPERATIONS. PMID- 17864364 TI - PERFORATING GASTRIC AND DUODENAL ULCER. PMID- 17864365 TI - PERSISTENCE OF PYLORIC AND DUODENAL ULCERS, FOLLOWING SIMPLE SUTURE OF AN ACUTE PERFORATION. PMID- 17864366 TI - CARCINOMA OF THE DUODENUM. PMID- 17864367 TI - PTOSIS OF THE THIRD PORTION OF THE DUODENUM WITH OBSTRUCTION AT THE DUODENO JEJUNAL JUNCTION. PMID- 17864368 TI - JEJUNO-COLIC FISTULA. PMID- 17864369 TI - THE RELATION BETWEEN INTESTINAL DAMAGE AND DELAYED OPERATION IN ACUTE MECHANICAL ILEUS. PMID- 17864370 TI - THE ORTHOPAEDIC TREATMENT OF BURNS. PMID- 17864371 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting held May 10, 1920. PMID- 17864372 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting held May 12, 1920. PMID- 17864373 TI - MULTIPLE POLYPOSIS OF THE INTESTINAL TRACT. PMID- 17864374 TI - A CASE OF DIAPHRAGMATIC HERNIA OBSERVED POST-MORTEM. PMID- 17864375 TI - HERNIA OF THE DIAPHRAGM. PMID- 17864376 TI - DIRECT INGUINAL HERNIA. PMID- 17864377 TI - DEVELOPMENT OF AN INGUINAL HERNIA THROUGH THE FEMORAL RING FOLLOWING DESCENT OF THE TESTICLE BY THE SAME ROUTE. PMID- 17864378 TI - AN OPERATION TO FORM A NEW ANAL SPHINCTER AFTER OPERATIONS ON THE LOWER RECTUM. PMID- 17864379 TI - TECHNIC OF PARTIAL COLECTOMY BY THE MIKULICZ TWO-STAGE METHOD. PMID- 17864380 TI - PRIMARY CARCINOMA OF THE VERMIFORM APPENDIX IN SISTERS SUFFERING FROM TUBERCULOSIS. PMID- 17864381 TI - RADICAL OPERATION IN CASES OF ADVANCED CANCER. PMID- 17864382 TI - RADIUM IN THE TREATMENT OF CARCINOMA OF THE CERVIX UTERI: A DISCUSSION OF THE PROBLEMS CONNECTED WITH THE OPERATIVE AND RADIUM TREATMENT. PMID- 17864383 TI - BONE TUMORS. MYXOMA, CENTRAL AND PERIOSTEAL: THEIR RECURRENCE AFTER EXPLORATORY EXCISION AND PIECEMEAL REMOVAL. PMID- 17864384 TI - HYPOPHYSEAL DUCT TUMORS: A REPORT OF THREE CASES AND A FOURTH CASE OF CYST OF RATHKE'S POUCH. PMID- 17864385 TI - THE WAR'S CONTRIBUTION TO CIVIL SURGERY. PMID- 17864386 TI - SEHRT'S METAL TOURNIQUET FOR PRODUCING ARTIFICIAL ANAEMIA. PMID- 17864387 TI - FIBROMYOMA OF THE CAECUM. PMID- 17864388 TI - A NEW GASTRO-ENTEROSTOMY CLAMP. PMID- 17864390 TI - BONE GRAFTING: STUDY OF SERIES OF CASES OPERATED IN U. S. ARMY HOSPITALS. PMID- 17864389 TI - THE RELATIVE PLACE OF PLASTER DRESSING AND OF SUSPENSION APPARATUS IN THE TREATMENT OF FRACTURES. PMID- 17864391 TI - EXSTROPHY OF THE BLADDER IN THE FEMALE: REPORT OF A SUCCESSFULLY OPERATED BY THE EXTRAPERITONEAL METHOD. PMID- 17864393 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting held October 4, 1920. PMID- 17864392 TI - GELATINIFORM CARCINOMA OF THE BREAST. PMID- 17864395 TI - PICRIC ACID IN OPERATIVE SURGERY. PMID- 17864394 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting held October 13, 1920. PMID- 17864396 TI - INTRACRANIAL AEROCELE FOLLOWING FRACTURED SKULL. PMID- 17864398 TI - BRONCHO-PULMONARY FISTULA: ITS IMPORTANCE AS A FACTOR IN ACUTE AND CHRONIC EMPYEMA. PMID- 17864399 TI - THE BACTERIOLOGY OF INFECTED WOUNDS WITH ESPECIAL REFERENCE TO THE IMPORTANCE OF STREPTOCOCCUS HAEMOLYTICUS. PMID- 17864397 TI - SQUAMOUS-CELL EPITHELIOMA OF THE THYROID. PMID- 17864400 TI - OBSERVATIONS ON CHOLELITHIASIS. PMID- 17864401 TI - THE PRODUCTION BY CHEMICAL MEANS OF A SPECIFIC CHOLECYSTITIS. PMID- 17864402 TI - HEMORRHAGIC CYSTS OF THE SPLEEN. PMID- 17864404 TI - RENAL TUBERCULOSIS IN TWINS. PMID- 17864403 TI - POLYCYSTIC KIDNEYS AND LIVER. PMID- 17864405 TI - THE TECHNIC OF THE OPERATIVE TREATMENT OF NEOPLASMS OF THE URINARY BLADDER. PMID- 17864406 TI - TIBIAL TUBERCLE AFFECTIONS: REPORT OF SEVEN CASES. PMID- 17864407 TI - HYSTERECTOMY IN THE LANKENAU (FORMERLY THE GERMAN) HOSPITAL: REPORT OF ONE YEAR'S (1919) WORK INCLUDING THE WRITER'S EXPERIENCE WITH RADIUM IN UTERINE CONDITIONS DURING THE YEAR, AND REMARKS UPON THE PATHOLOGY: BY STANLEY P. REIMANN, DIRECTOR OF THE PATHOLOGICAL LABORATORIES, LANKENAU HOSPITAL. PMID- 17864409 TI - SQUAMOUS-CELL EPITHELIOMA OF THE SKIN: A STUDY OF 256 CASES. PMID- 17864408 TI - NOTES ON THE NON-OPERATIVE TREATMENT OF FRACTURES. PMID- 17864410 TI - PAINLESS HYPODERMOCLYSIS. PMID- 17864411 TI - REGIONAL ANAESTHESIA: A SHORT REVIEW OF THE GENERAL PRINCIPLES. PMID- 17864412 TI - SOME SURGICAL ASPECTS OF ASPHYXIA. PMID- 17864413 TI - SOME UNDERLYING PRINCIPLES OF INTESTINAL AND GASTRIC SURGERY. PMID- 17864415 TI - STAVE FRACTURE OF THE FIRST METATARSAL BONE. PMID- 17864414 TI - SOLID TUMORS OF THE MESENTERY. PMID- 17864416 TI - TUMORS IN SOUTH CHINA: BASED UPON RECORDS OF OPERATIONS PERFORMED IN THE CANTON HOSPITAL DURING THE TEN YEARS 1910 TO 1919. PMID- 17864417 TI - PSEUDO-POLYCYTHEMIA: EXTRAORDINARY BLOOD-CHANGES IN A PATIENT WITH RENAL CALCULUS. PMID- 17864418 TI - PERTROCHANTERIC FRACTURE OF THE FEMUR. PMID- 17864420 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting held October 27, 1920. PMID- 17864419 TI - MESENTERIC EMBOLISM IN A HAEMOPHILIAC. PMID- 17864421 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting held November 10, 1920. PMID- 17864423 TI - PRELIMINARY LIGATION OF COMMON ILIAC ARTERY IN HIP-JOINT EXARTICULATION. PMID- 17864422 TI - LIGATION OF THE EXTERNAL ILIAC ARTERY AND VEIN ABOVE AND BELOW A COMMUNICATING BULLET WOUND OF THESE TWO VESSELS. PMID- 17864424 TI - CANCER INFECTION. PMID- 17864425 TI - CARCINOMA OF THE KIDNEY. PMID- 17864426 TI - CARCINOMA OF THE PELVIS OF THE KIDNEY. PMID- 17864428 TI - LARYNGEAL FUNCTION IN THYROID CASES. PMID- 17864427 TI - END-RESULTS OF OPERATIONS FOR BONY ANKYLOSIS OF THE JAW. PMID- 17864429 TI - GASTRIC AND DUODENAL ULCERS. PMID- 17864430 TI - SUBPHRENIC PYOPNEUMOTHORAX-SUBPHRENIC ABSCESS. PMID- 17864431 TI - THE TECHNIC OF HEPATICODUODENOSTOMY, WITH SOME NOTES ON RECONSTRUCTIVE SURGERY OF THE BILIARY DUCTS. PMID- 17864432 TI - AN ANALYTICAL STUDY OF FIFTY CASES OF URETERAL STRICTURE AND PYELITIS. PMID- 17864434 TI - OPERATIVE TREATMENT OF GONORRHOEAL EPIDIDYMITIS. PMID- 17864433 TI - EXSTROPHY OF THE URINARY BLADDER WITH CARCINOMA. PMID- 17864435 TI - COMPRESSION FRACTURE OF THE FIRST LUMBAR VERTEBRA WITH DELAYED SYMPTOMS (KUEMMEL'S DISEASE). PMID- 17864437 TI - TECHNIC FOR REMOVAL OF FOREIGN BODIES UNDER DIRECT FLUOROSCOPIC GUIDANCE. PMID- 17864436 TI - RONTGENOGRAPHIC STUDIES OF BRONCHIECTASIS AND LUNG ABSCESS AFTER DIRECT INJECTION OF BISMUTH MIXTURE THROUGH THE BRONCHOSCOPE. PMID- 17864438 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting held November 1, 1920. PMID- 17864439 TI - EDITORIAL COMMENT. PMID- 17864440 TI - PERICARDIOTOMY FOR SUPPURATIVE PERICARDITIS. PMID- 17864442 TI - THE PRESENT STATUS OF GASTRIC AND DUODENAL ULCER. PMID- 17864441 TI - DIAPHRAGMATIC HERNIA. PMID- 17864443 TI - MARGINAL, GASTROJEJUNAL OR PEPTIC ULCER SUBSEQUENT TO GASTROENTEROSTOMY. PMID- 17864444 TI - GASTROENTEROSTOMY IN ACUTE PERFORATED ULCER OF THE STOMACH AND DUODENUM. PMID- 17864446 TI - DRAINAGE OF THE COMMON BILE DUCT THROUGH THE CYSTIC DUCT: CYSTICO CHOLEDOCHOSTOMY. PMID- 17864445 TI - COMPARATIVE RESULTS OF PYLOROPLASTY AND OF GASTRO-ENTEROSTOMY IN STOMACH SURGERY. PMID- 17864448 TI - THE GIBSON-MIKULICZ TAMPON IN ACUTE APPENDICITIS. PMID- 17864447 TI - THE RUBBER DAM MIKULICZ TAMPON. PMID- 17864449 TI - CONGENITAL VALVES OF THE POSTERIOR URETHRA. PMID- 17864450 TI - KRUKENBERG TUMOR OF THE OVARY. PMID- 17864451 TI - THE TREATMENT OF UNUNITED FRACTURES. PMID- 17864452 TI - AN INTEGRAL TRACTION-PROVIDING SPLINT FOR VICIOUS FRACTURES OF THE FEMUR. PMID- 17864453 TI - THREE FREQUENT CAUSES OF WEAK AND OF FLAT FEET. PMID- 17864454 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY JOINT MEETING WITH PHILADELPHIA ACADEMY OF SURGERY December 8, 1920. PMID- 17864455 TI - THE RESULTS OF SURGICAL TREATMENT OF EPITHELIOMA OF THE LIP. PMID- 17864456 TI - SALIVARY CALCULUS IN AN ACROMEGALIC. PMID- 17864457 TI - THE TREATMENT OF ACUTE SUPPURATIVE PLEURISY. PMID- 17864458 TI - DUODENAL ULCER IN INFANCY. PMID- 17864459 TI - LINITIS PLASTICA. PMID- 17864460 TI - THE USE OF THE DUODENAL TUBE IN THE PRE-OPERATIVE STUDY OF THE BACTERIOLOGY AND PATHOLOGY OF THE BILIARY TRACT AND PANCREAS. PMID- 17864461 TI - ACUTE INTESTINAL OBSTRUCTION DUE TO STRANGULATION OF A LOOP OF SMALL INTESTINE BY MECKEL'S DIVERTICULUM. PMID- 17864462 TI - CHRONIC DUODENAL OBSTRUCTION WITH DUODENO-JEJUNOSTOMY AS A METHOD OF TREATMENT: REPORT OF FORTY-ONE OPERATIONS. PMID- 17864463 TI - SYMPHYSIOTOMY AS AN AID TO THE REMOVAL OF CANCER OF THE PROSTATE: A PROPOSED NEW OPERATION. PMID- 17864465 TI - SLIDING HERNIA OF THE URETER. PMID- 17864464 TI - THE SECRETORY PRESSURE OF THE KIDNEY AS AN INDEX OF PATHOLOGIC CONDITIONS: PRELIMINARY REPORT. PMID- 17864466 TI - DISLOCATIONS OF THE SEMILUNAR CARPAL BONE. PMID- 17864468 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting held January 3, 1921. PMID- 17864467 TI - INJURY TO THE BILE DUCTS AND METHODS OF REPAIR. PMID- 17864469 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting held January 12, 1921. PMID- 17864470 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting held January 26, 1921. PMID- 17864471 TI - A GRAVIMETRIC METHOD FOR DETERMINING THE SUPERFICIAL AREA OF WOUNDS: A PRELIMINARY REPORT. PMID- 17864472 TI - ACUTE HAEMATOGENOUS OSTEOMYELITIS. PMID- 17864473 TI - TREATMENT OF AN OPEN INFECTED WOUND. PMID- 17864475 TI - TREATMENT OF CARCINOMA OF THE TONGUE. PMID- 17864474 TI - RECURRENT UNILATERAL SUBLUXATION OF THE MANDIBLE EXCISION OF THE INTERARTICULAR CARTILAGE IN CASES OF SNAPPING JAW. PMID- 17864476 TI - BENIGN STENOSIS OF THE OESOPHAGUS: WITH A REPORT OF EIGHT CASES. PMID- 17864477 TI - MECHANICAL FACTORS IN THE MANAGEMENT OF RECENT EMPYEMAS. PMID- 17864478 TI - CLINICALLY DOUBTFUL BREAST TUMORS: THEIR DIAGNOSIS AND TREATMENT. PMID- 17864479 TI - CULTURES FROM THE APPENDIX. PMID- 17864481 TI - CANCER OF THE LARGE INTESTINE: NOT INCLUDING THE RECTUM AND RECTOSIGMOID. PMID- 17864480 TI - RESULTS OF TREATMENT OF TWENTY RECENT CASES OF INTRACAPSULAR FRACTURE OF THE FEMUR BY ABDUCTION AND PLASTER FIXATION. PMID- 17864482 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 7, 1921: Stated Meeting Held February. PMID- 17864483 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 9, 1921: Regular Meeting Held February. PMID- 17864484 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 23, 1921: Stated Meeting Held February. PMID- 17864486 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held March 7, 1921. PMID- 17864485 TI - RUPTURED SPLEENS. SPONTANEOUS AND SUBCUTANEOUS. PMID- 17864488 TI - THE EFFICIENT TREATMENT OF FRACTURES OF THE NECK OF THE FEMUR. PMID- 17864487 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held March 9, 1921. PMID- 17864489 TI - SURGERY OF CYSTS OF THE SPLEEN. PMID- 17864491 TI - THE SURGERY OF INFANTILE PARALYSIS. PMID- 17864490 TI - TECHNIC OF NERVE SURGERY. PMID- 17864492 TI - FRACTURE OF THE SKULL IN CHILDREN: A STATISTICAL SURVEY OF 100 CASES. PMID- 17864494 TI - PRIMARY CLOSURE OF THE URETER AND RENAL PELVIS AFTER NEPHROLITHOTOMY. PMID- 17864493 TI - THE VALUE OF DAKIN'S SOLUTION IN THE TREATMENT OF THORACIC EMPYEMA. PMID- 17864496 TI - DIVERTICULA OF THE JEJUNUM. PMID- 17864495 TI - URETERO-URETERAL ANASTOMOSIS: A MODIFICATION OF VAN HOOK'S TECHNIQUE. PMID- 17864497 TI - MALIGNANT TUMORS OF THE THYROID. PMID- 17864498 TI - CLINICAL EXPERIENCE WITH SYNERGISTIC ANALGESIA. PMID- 17864500 TI - RESULTS OF TREATMENT OF 115 CASES OF FRACTURE OF THE SHAFT OF THE FEMUR AT THE UNIVERSITY OF PENNSYLVANIA HOSPITAL. PMID- 17864499 TI - CERTAIN FUNDAMENTAL LAWS UNDERLYING THE SURGICAL USE OF THE BONE GRAFT. PMID- 17864501 TI - FRACTURE OF THE METATARSAL BONES: WITH A REPORT OF FOUR CASES. PMID- 17864502 TI - CHORIO-EPITHELIOMA FOLLOWING HYDATIFORM DEGENERATION: WITH REMARKS ON THE USE OF RADIUM. PMID- 17864503 TI - PERFORATED GASTRIC AND DUODENAL ULCER WITHOUT PREVIOUS PAIN. PMID- 17864504 TI - POLYPOID LIPOMA OF THE INTESTINAL TRACT. PMID- 17864506 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 23, 1921: Stated Meeting Held March. PMID- 17864505 TI - MYOMA OF THE RECTUM: REPORT OF FOUR CASES. PMID- 17864507 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 4, 1921: Stated Meeting Held April. PMID- 17864508 TI - DISLOCATIONS OF THE SEMILUNAR CARPAL BONE. PMID- 17864509 TI - THE MAKING OF A SURGEON. PMID- 17864511 TI - CERTAIN PROBLEMS CONCERNING FRACTURES OF BONE. PMID- 17864510 TI - CARCINOMA OF THORACIC OESOPHAGUS EXTRAPLEURAL RESECTION AND PLASTIC: DESCRIPTION OF AN ORIGINAL METHOD WITH REPORT OF A SUCCESSFUL CASE WITHOUT GASTROSTOMY. PMID- 17864512 TI - THE VALUES OF THE VARIOUS METHODS OF BONE GRAFTINGS JUDGED BY 1390 REPORTED CASES. PMID- 17864514 TI - THE INFLUENCE OF PHYSICAL THERAPY IN REDUCING DISABILITY TIME IN FRACTURES OF THE LONG BONES. PMID- 17864513 TI - OLD OS CALCIS FRACTURES. PMID- 17864515 TI - OPERATION FOR THE CURE OF ANEURISM. PMID- 17864516 TI - LIGATION (PARTIAL OCCLUSION) OF THE ABDOMINAL AORTA FOR ANEURISM: Report of a Recent Case with a Resume of Previous Cases. PMID- 17864517 TI - A NOTE ON THE TREATMENT OF SECONDARY HEMORRHAGE FROM THE BRANCHES OF THE COMMON CAROTID ARTERY. PMID- 17864519 TI - SURGICAL ASPECT OF TUMOR OF THE BRAIN. PMID- 17864518 TI - THE CAUSATION AND AVOIDANCE OF CEREBRAL DISTURBANCES IN LIGATION OF THE COMMON CAROTID ARTERY. PMID- 17864520 TI - A SURGICAL APPROACH TO THE SPHENOPALATINE GANGLION. PMID- 17864521 TI - ATROPHY AND INACTIVITY OF PAROTID GLAND, FOLLOWING OPERATIVE OBLITERATION OF STENSON'S DUCT, IN CARCINOMA OF THE CHEEK. PMID- 17864522 TI - AN ANALYSIS OF 102 CASES OF TUMORS OF THE BREAST. PMID- 17864523 TI - DIAPHRAGMATIC HERNIA; THE THORACIC APPROACH. PMID- 17864524 TI - PERNICIOUS ANAEMIA WITH SPECIAL REFERENCE TO THE SPLEEN AND THE LARGE INTESTINE. PMID- 17864525 TI - SOME SECONDARY COMPLICATIONS OF POSTERIOR GASTRO-ENTEROSTOMY. PMID- 17864527 TI - SO-CALLED CONGENITAL DISLOCATION OF THE SHOULDER POSTERIOR SUBLUXATION. PMID- 17864526 TI - TYPICAL FIBROMYOMA OF THE ABDOMINAL WALL FOLLOWING HYSTERECTOMY. PMID- 17864528 TI - STANDARDIZED RESULTS OF WOUND HEALING. PMID- 17864530 TI - SOME RESEARCHES ON THE PERI-ARTERIAL SYMPATHETICS. PMID- 17864529 TI - THE SURGICAL REMOVAL OF PANCREATIC STONES. PMID- 17864531 TI - THE SIMPLIFICATION OF TECHNIQUE IN OPERATIONS FOR HARE-LIP AND CLEFT PALATE. PMID- 17864532 TI - FURTHER DATA CONCERNING THE EXPERIMENTAL PRODUCTION OF PANCREATITIS. PMID- 17864533 TI - DRAINAGE OF ABSCESS OF PANCREAS. PMID- 17864534 TI - TRAUMATIC PANCREATITIS. PMID- 17864535 TI - CHRONIC CHOLECYSTITIS WITHOUT STONES: DIAGNOSIS AND TREATMENT. PMID- 17864536 TI - SURGICAL MANAGEMENT OF GASTRIC ULCERS. PMID- 17864537 TI - THE ALTERED ANATOMY AND PHYSIOLOGY OF THE CAECUM AND ASCENDING COLON, THE RESULT OF ADHESIONS. PMID- 17864538 TI - CARCINOMA OF THE LOWER PART OF THE SIGMOID IN A BOY FOURTEEN YEARS OF AGE. PMID- 17864539 TI - THE SURGICAL TREATMENT OF MEGACOLON. PMID- 17864541 TI - ON THE MECHANICS OF PRODUCTION AND THE TREATMENT OF SPIRAL FRACTURES. PMID- 17864540 TI - THE MANAGEMENT OF PELVIC ABSCESS IN ACUTE APPENDICITIS. PMID- 17864542 TI - INEQUALITY OF THE LOWER EXTREMITIES FOLLOWING FRACTURE OF THE SHAFT OF THE FEMUR IN CHILDREN. PMID- 17864544 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held April 27, 1921. PMID- 17864543 TI - NOTE CONCERNING KERATIN AND KERATOHYALIN IN TUMORS OF THE HYPOPHYSIAL DUCT. PMID- 17864545 TI - RUPTURE OF UTERUS. PMID- 17864547 TI - TRANS-ORBITAL PUNCTURE OF THE GASSERIAN GANGLION. PMID- 17864546 TI - RESULTS OF TWENTY-ONE CASES OF SURGICAL TREATMENT OF ANEURISM. PMID- 17864548 TI - A STUDY OF METHODS OF PROCEDURE IN RESECTION OF THE OESOPHAGUS. PMID- 17864549 TI - OBSERVATIONS UPON THE SURGERY OF THE LUNG. PMID- 17864550 TI - GANGRENE OF AN EXTREMITY AS A COMPLICATION OF PNEUMONIA. PMID- 17864552 TI - PEPTIC ULCER, PRIMARY AND SECONDARY. PMID- 17864551 TI - CENTRAL BONE ABSCESS: BRODIE'S ABSCESS; CHRONIC SUPPURATIVE OSTEOMYELITIS. PMID- 17864553 TI - EXPERIMENTAL INTESTINAL OBSTRUCTION: A STUDY IN SEVERED GUT OBSTRUCTION AND SEGMENTAL OBSTRUCTION. PMID- 17864555 TI - INCOMPLETE RUPTURE OF THE AXILLARY ARTERY. PMID- 17864554 TI - A FUNDAMENTALLY NEW TECHNIC FOR INGUINAL HERNIOTOMY. PMID- 17864556 TI - ARTERIAL HAEMATOMA FOLLOWING TRAUMATIC RUPTURE OF THE POPLITEAL ARTERY. PMID- 17864558 TI - A TECHNIC FOR LEG AMPUTATION. PMID- 17864557 TI - FRAGILITAS OSSIUM. PMID- 17864559 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held April 13, 1921. PMID- 17864561 TI - LATEST ACHIEVEMENTS OF THE ART OF LOCAL, REGIONAL AND SPINAL ANAESTHESIA. PMID- 17864560 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held May 11, 1921. PMID- 17864563 TI - TRAUMATIC CHYLOTHORAX. PMID- 17864562 TI - THE MALIGNANT DEGENERATION OF BENIGN TUMORS OF THE THYROID GLAND. PMID- 17864564 TI - AN ANOMALOUS PORTAL VEIN WITH ITS SURGICAL DANGERS. PMID- 17864565 TI - MALIGNANT NEOPLASIA IN THE GALL-BLADDER. PMID- 17864566 TI - PERFORATING GASTRIC AND DUODENAL ULCER. PMID- 17864567 TI - PERSISTENCE OF GASTRIC ULCER AFTER GASTROENTEROSTOMY. PMID- 17864569 TI - RADIUM TREATMENT OF CARCINOMA OF THE BLADDER. PMID- 17864568 TI - JEJUNAL DIVERTICULA. PMID- 17864570 TI - HAEMOSTASIS IN SUPRAPUBIC PROSTATECTOMY BY THE METHOD OF THE "LOST TAMPON". PMID- 17864572 TI - ON THE TRAUMATOLOGY OF THE SESAMOID STRUCTURES. PMID- 17864571 TI - DEFECTS OF THE PATELLAR BORDER. PMID- 17864573 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held May 2, 1921. PMID- 17864574 TI - NEW MECHANICAL PROBLEMS IN THE BRONCHOSCOPIC EXTRACTION OF FOREIGN BODIES FROM THE LUNGS AND OESOPHAGUS. PMID- 17864575 TI - POSTURE AND THE CERVICAL RIB SYNDROME. PMID- 17864577 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 12, 1921: Stated Meeting Held October. PMID- 17864576 TI - THE INTRA-ABDOMINAL OPERATION FOR FEMORAL HERNIA. PMID- 17864578 TI - FRACTURE OF THE METATARSAL BONES-BLOODLESS REDUCTION. PMID- 17864580 TI - WOUND EXCISION AND EARLY RECONSTRUCTION IN THE TREATMENT OF COMPOUND FRACTURES. PMID- 17864579 TI - THE SURGICAL TREATMENT OF PERNICIOUS ANAEMIA. PMID- 17864581 TI - SPECIAL POINTS IN THE TECHNIC OF OPERATIONS ON THE THYROID GLAND. PMID- 17864583 TI - LIFE EXPECTANCY FOLLOWING RADICAL AMPUTATION FOR CARCINOMA OF THE BREAST: A CLINICAL AND PATHOLOGIC STUDY OF 218 CASES. PMID- 17864582 TI - NOTES ON SURGERY OF THE MEDIASTINUM. PMID- 17864584 TI - THE TRANSVERSE ABDOMINAL INCISION. PMID- 17864585 TI - ACUTE INTESTINAL OBSTRUCTION: ENTERECTOMY, PARTIAL EXCISION, INCLUSION, POST APPENDICAL INCIDENCE, TREATMENT OF STUMPS. PMID- 17864586 TI - RECTAL AND VESICAL INCONTINENCE RELIEVED BY OPERATION. PMID- 17864588 TI - THE RELATIONSHIP OF MASSAGE TO METASTASIS IN MALIGNANT TUMORS. PMID- 17864587 TI - SECONDARY FOCI OF TUBERCULOSIS IN THE SPINE IN POTTS' DISEASE. PMID- 17864589 TI - TREATMENT OF ERYSIPELAS WITH CHINOSOL AND SODIUM CHLORIDE. PMID- 17864590 TI - VON RECKLINGHAUSEN'S DISEASE OR OSTEITIS FIBROSA: WITH REPORT OF A CASE PRESENTING MULTIPLE CYSTS AND GIANT-CELL TUMORS. PMID- 17864591 TI - NEURO-FIBRO-MYXOMA TREATED BY CONSERVATIVE OPERATION. PMID- 17864592 TI - RUPTURED SPLEEN: WITH REPORT OF THREE CASES. PMID- 17864593 TI - CYSTIC DILATATION OF THE COMMON BILE DUCT. PMID- 17864594 TI - SOME PROBLEMS IN CONNECTION WITH THE SURGERY OF THE BILIARY TRACT. PMID- 17864596 TI - DUODENECTOMY: AN EXPERIMENTAL STUDY. PMID- 17864595 TI - THE RESULTS OF HIGH LIGATION OF THE CYSTIC DUCT IN CHOLECYSTECTOMY. PMID- 17864598 TI - DISLOCATION OF THE PISIFORM. PMID- 17864597 TI - A COMPARATIVE ANALYSIS OF 213 FOREARM AND LEG FRACTURES. PMID- 17864599 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held October 3, 1921. PMID- 17864600 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held October 26, 1921. PMID- 17864601 TI - THE USE OF FASCIA LATA TO REPAIR DEFECT OF HEEL. PMID- 17864602 TI - GUNSHOT WOUND OF HORSE-SHOE KIDNEY-GUNSHOT WOUND OF EXTERNAL ILIAC ARTERY. PMID- 17864603 TI - PARALYSIS FOLLOWING USE OF SEHRT'S TOURNIQUET. PMID- 17864604 TI - RESECTION OF THE LUNG FOR SUPPURATIVE INFECTIONS WITH A REPORT BASED ON 31 OPERATIVE CASES IN WHICH RESECTION WAS DONE OR INTENDED. PMID- 17864606 TI - ABERRANT ADENOID CYSTIC EPITHELIOMAS OF THE SALIVARY GLAND TYPE. PMID- 17864605 TI - THE PATHOLOGY OF LUNG SUPPURATION. PMID- 17864607 TI - DIAPHRAGMATIC HERNIA. PMID- 17864608 TI - HEPATICODUODENOSTOMY FOR INJURY OF THE BILE DUCTS DURING CHOLECYSTECTOMY. PMID- 17864609 TI - ACUTE PERFORATED ULCER OF THE STOMACH OR DUODENUM. PMID- 17864611 TI - THE POTENTIAL MALIGNANCY IN EXSTROPHY OF THE BLADDER. PMID- 17864610 TI - BLIND-END CIRCULAR SUTURE OF THE INTESTINE, CLOSED ENDS ABUTTED AND THE DOUBLE DIAPHRAGM PUNCTURED WITH A KNIFE INTRODUCED PER RECTUM. PMID- 17864612 TI - INTERMITTENT HYDRONEPHROSIS WITH GASTROENTEROLOGIC SYMPTOMS. PMID- 17864614 TI - DRAINAGE. PMID- 17864613 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held December 14, 1921. PMID- 17864615 TI - WAR INJURIES COMING TO SUBSEQUENT OPERATION. PMID- 17864616 TI - THE TREATMENT OF SURGICAL TUBERCULOSIS WITH THE CARBON-ARC LAMP. PMID- 17864617 TI - TUBERCULOUS ABSCESSES OF THE CHEST WALL. PMID- 17864619 TI - LETHAL FACTORS IN ACUTE ILEUS. PMID- 17864618 TI - OBSERVATIONS ON A CASE OF POST-OPERATIVE TETANY WITH IMPLANTATION OF HUMAN PARATHYROIDS. PMID- 17864620 TI - THE CAUSE OF DEATH IN HIGH INTESTINAL OBSTRUCTION. PMID- 17864622 TI - BLEEDING ULCER OF THE DUODENUM ASSOCIATED WITH CHOLECYSTITIS. PMID- 17864621 TI - THE PRESENT STATUS OF EPIPLOPEXY: WITH THE REPORT OF TEN CASES. PMID- 17864623 TI - TRAUMATIC AND INDUSTRIAL HERNIA: REPORT OF THE SPECIAL COMMITTEE OF THE MEDICAL SECTION OF THE AMERICAN RAILWAY ASSOCIATION. PMID- 17864625 TI - NOTE ON THE DIAGNOSIS OF SHADOWLESS RENAL CALCULI: WITH ESPECIAL REFERENCE TO THOSE OF CYSTIN COMPOSITION. PMID- 17864624 TI - NON-TUBERCULAR KIDNEY INFECTIONS. PMID- 17864626 TI - INTRA-ABDOMINAL HEMORRHAGE FROM RUPTURED CORPUS LUTEUM. PMID- 17864627 TI - PREMATURE OSSIFICATION AFTER SEPARATION OF THE LOWER RADIAL EPIPHYSIS. PMID- 17864629 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held December 5, 1921. PMID- 17864628 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Joint Meeting with the New York Surgical Society held November 7, 1921. PMID- 17864631 TI - EPITHELIOMA OF THE GENITO-URINARY ORGANS. PMID- 17864630 TI - ANOMALOUS ABDOMINAL MEMBRANES: THEIR INFLUENCE UPON THE DIGESTIVE TRACT. PMID- 17864632 TI - CARCINOMATOUS PAPILLOMA OF THE RENAL PELVIS. PMID- 17864633 TI - HERNIA OF THE BLADDER. PMID- 17864634 TI - GAS CYSTS OF THE INTESTINES. PMID- 17864636 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held January 11, 1922. PMID- 17864635 TI - TRAUMATIC DIAPHRAGMATIC HERNIA. PMID- 17864637 TI - OSTEOPHYTIC ANKYLOSIS OF ELBOW. PMID- 17864638 TI - UMBILICAL AND INGUINO-LABIAL HERNIA IN WOMAN OF ADVANCED AGE. PMID- 17864639 TI - TUMORS OF THE BREAST: BENIGN AND MALIGNANT-A REVIEW OF 331 CASES. PMID- 17864640 TI - PAPILLARY CYSTADENOMA OF THE MALE BREAST. PMID- 17864641 TI - AN IMPROVED METHOD OF SKIN-GRAFTING. PMID- 17864642 TI - THE SERUM TREATMENT OF ANTHRAX SEPTICAEMIA. PMID- 17864644 TI - SCIATIC HERNIA: REPORT OF A CASE COMPLICATED WITH MYXOMATOUS TUMOR OF THE SCROTUM. PMID- 17864643 TI - PERITONITIS AS A COMPLICATION OF PROSTATECTOMY. PMID- 17864645 TI - SPONTANEOUS LATERAL VENTRAL HERNIA. PMID- 17864646 TI - THE LOW TRANSVERSE INCISION IN OPERATIONS UPON THE THYROID GLAND. PMID- 17864647 TI - EXTRACRANIAL ANEURISM OF THE INTERNAL CAROTID: REPORT OF A CASE. PMID- 17864648 TI - ANOTHER CASE OF BULLET WOUND OF THE FEMORAL ARTERY AND VEIN SUCCESSFULLY TREATED BY LIGATION OF THE ARTERY AND VEIN AND EXTIRPATION OF THE INJURED SEGMENT. PMID- 17864650 TI - SPIRAL FRACTURE OF THE TIBIA AND FIBULA. PMID- 17864649 TI - THE VALUE OF DAKIN'S SOLUTION IN THE TREATMENT OF ACUTE AND CHRONIC OSTEOMYELITIS. PMID- 17864651 TI - VOLVULUS OF THE SIGMOID. PMID- 17864652 TI - VALUE OF BLOOD-PRESSURE IN ACUTE CEREBRAL COMPRESSION: AN EXPERIMENTAL AND CLINICAL STUDY. PMID- 17864653 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held January 9, 1922. PMID- 17864654 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held January 25, 1922. PMID- 17864655 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held February 8, 1922. PMID- 17864658 TI - SURGICAL TREATMENT OF UTERINE PROLAPSE: END RESULT IN THIRTY CASES. PMID- 17864656 TI - INTRAMUSCULAR ADMINISTRATION OF SODIUM CITRATE. PMID- 17864657 TI - FIBROUS TUMORS OF THE FOOT. PMID- 17864660 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 6, 1922: Stated Meeting Held February. PMID- 17864659 TI - NEW MECHANICS IN BONE INJURIES. PMID- 17864661 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 8, 1922: Stated Meeting Held March. PMID- 17864662 TI - STAPHYLOCOCCUS INFECTIONS OF THE FACE AND LIPS. PMID- 17864663 TI - HAEMANGIOMAS OF THE GASTRO-INTESTINAL TRACT. PMID- 17864664 TI - MODIFICATION OF THE KADER OPERATION. PMID- 17864665 TI - ACUTE PERFORATIONS OF THE STOMACH AND DUODENUM. PMID- 17864666 TI - DUODENAL DIVERTICULA. PMID- 17864667 TI - TUMORS OF THE KIDNEY IN INFANCY AND CHILDHOOD. PMID- 17864668 TI - INTRAPERITONEAL RUPTURE OF THE BLADDER. PMID- 17864669 TI - CONGENITAL DISLOCATION OF THE SHOULDER. PMID- 17864670 TI - FRACTURES OF THE CAPITELLUM AND TROCHLEA. PMID- 17864671 TI - INJURY OF THE LIMBS DUE TO BACK-FIRE. PMID- 17864672 TI - LONGEVITY IN CANCER: A STUDY OF 293 CASES. PMID- 17864674 TI - PLASTIC SURGERY OF THE FACE. PMID- 17864673 TI - TRANSPLANTATION OF FIBULA. PMID- 17864675 TI - HARELIP AND CLEFT-PALATE DEFORMITIES, SOME OF THE TYPES AND THEIR OPERATIVE TREATMENT. PMID- 17864676 TI - OPERATIVE TREATMENT OF COMPLETE DOUBLE HARELIP. PMID- 17864677 TI - EXPERIMENTAL RECONSTRUCTION OF THE OESOPHAGUS WITH AUTOGENOUS FASCIA LATA TRANSPLANTS. PMID- 17864678 TI - EXTIRPATION OF ONE (LEFT) ADRENAL GLAND FOR THE CURE OF EPILEPSY. PMID- 17864680 TI - THE SURGICAL TREATMENT OF CHOLELITHIASIS, CHOLECYSTECTOMY AND CHOLEDOCHOTOMY: CONTINUOUS OUT-DOOR TREATMENT. PMID- 17864679 TI - THE SURGICAL VALUE OF THE ESTIMATION OF THE BILE PIGMENTATION (ICTERUS INDEX) OF THE BLOOD SERUM. PMID- 17864681 TI - MALIGNANT NEOPLASMS OF THE EXTRAHEPATIC BILIARY DUCTS. PMID- 17864683 TI - LYMPHOSARCOMA OF THE INTESTINE. PMID- 17864682 TI - PERFORATION OF DUODENAL ULCER FOLLOWING GASTRO-ENTEROSTOMY. PMID- 17864684 TI - METAPLASIA IN OVARIAN DERMOIDS AND CYSTADENOMAS: REPORT OF THREE CASES. PMID- 17864685 TI - PRIMARY TUMORS OF THE URETHRA. PMID- 17864686 TI - MALIGNANCY OF THE UNDESCENDED TESTIS-ASSOCIATED WITH HYDROCELE. PMID- 17864688 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held March 6, 1922. PMID- 17864689 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held April 12, 1922. PMID- 17864687 TI - RESULTS OF TREATMENT IN FORTY-EIGHT CASES OF SCIATICA. PMID- 17864691 TI - END RESULTS IN CANCER AS INFLUENCED BY TYPE, REACTION, LOCATION AND AGE. PMID- 17864690 TI - THE OPPORTUNITIES AND RESPONSIBILITIES OF THE SURGEON. PMID- 17864692 TI - THE SECONDARY MANIFESTATIONS OF MALIGNANT DISEASE. PMID- 17864693 TI - RECURRENCE VERSUS METASTASIS IN CARCINOMA. PMID- 17864694 TI - THE TREATMENT OF CANCER OF THE JAWS: OBSERVATIONS CONTINUED SINCE 1918, COVERING 26 ADDITIONAL CASES. PMID- 17864695 TI - CARCINOMA OF THE THORACIC OESOPHAGUS: FINAL NOTES AND POST-MORTEM EXAMINATION IN THE CASE REPORTED IN THE ANNALS OF SURGERY, SEPTEMBER, 1921. PMID- 17864696 TI - THE END RESULTS OF TREATMENT IN CERTAIN FORMS OF MALIGNANCY OF THE NECK. PMID- 17864697 TI - END RESULTS OF OPERATIONS FOR CANCER OF BREAST. PMID- 17864698 TI - END RESULTS OF OPERATIONS FOR CARCINOMA OF THE BREAST. PMID- 17864699 TI - THE END RESULTS OF OPERATIONS FOR CANCER OF THE BLADDER. PMID- 17864700 TI - RESULTS OF THE TREATMENT BY RADIATION OF PRIMARY INOPERABLE CARCINOMA OF THE BREAST: A REPORT OF 83 CASES TREATED IN THE BREAST CLINIC AT THE MEMORIAL HOSPITAL OF NEW YORK, N. Y. PMID- 17864702 TI - END RESULTS OF THE SURGICAL TREATMENT OF CARCINOMA OF THE CERVIX UTERI. PMID- 17864701 TI - END RESULTS OF OPERATIONS FOR CARCINOMA OF THE RECTUM. PMID- 17864703 TI - FACTORS INFLUENCING THE LIFE EXPECTANCY OF PATIENTS OPERATED ON FOR GASTRIC ULCER. PMID- 17864705 TI - THE SIGNIFICANCE OF BACTERIA IN THE BLOOD STREAM FROM A SURGICAL STANDPOINT. PMID- 17864704 TI - RESECTION OF THE BODY OF THE STOMACH FOR ULCER: REPORT OF A SERIES OF CASES WITH END RESULTS. PMID- 17864706 TI - THE PERITONEAL MANIFESTATIONS OF CHRONIC MULTIPLE SEROSITIS, CONCATO'S DISEASE. PMID- 17864707 TI - THYROID SURGERY AND THE DEMENTIA PRAECOX SYNDROME. PMID- 17864708 TI - CONGENITAL HYPERTROPHIC STENOSIS OF THE PYLORUS IN THE ADULT. PMID- 17864709 TI - SURGICAL TREATMENT OF SYPHILIS OF THE STOMACH. PMID- 17864710 TI - LATE RESULTS OF GASTRO-ENTEROSTOMY FOR GASTRIC AND DUODENAL ULCERS, INCLUDING ACUTE PERFORATED ULCERS. PMID- 17864711 TI - THE END RESULTS OF OPERATIONS FOR GASTRIC AND DUODENAL ULCER AND CANCER. PMID- 17864712 TI - THE RESULTS OF THE OPERATIVE TREATMENT OF CASES OF CHRONIC GASTRIC AND DUODENAL ULCER AT THE MASSACHUSETTS GENERAL HOSPITAL CLINIC. PMID- 17864714 TI - THE CHOICE OF OPERATION FOR GASTRIC ULCER IN VIEW OF THE LATE RESULTS. PMID- 17864713 TI - PEPTIC ULCER. PMID- 17864715 TI - A BACTERIOLOGIC STUDY OF THE FLUID CONTENTS OF 100 GALL-BLADDERS REMOVED AT OPERATION. PMID- 17864716 TI - TRAUMATIC PANCREATITIS. PMID- 17864717 TI - FAULTY ROTATION OF THE INTESTINE. PMID- 17864718 TI - PROLAPSE OF THE RECTUM IN CHILDREN: THE D'ESPINE METHOD OF TREATMENT. PMID- 17864719 TI - TREATMENT OF CANCER OF THE RECTUM. PMID- 17864720 TI - THE SURGICAL RELIEF OF INTESTINAL FOCI OF INFECTION IN CASES OF ARTHRITIS DEFORMANS. PMID- 17864721 TI - LIGATION OF THE AORTA: NECROPSY TWO YEARS AND ONE MONTH AFTER OPERATION. PMID- 17864722 TI - LIGATION OF THE INTERNAL ILIAC FOR ENORMOUS GLUTEAL ANEURISM. PMID- 17864723 TI - PERIPHERAL NERVE INJURIES ASSOCIATED WITH FRACTURES. PMID- 17864724 TI - BONE FORMATION IN OPERATIVE WOUND CICATRICES. PMID- 17864725 TI - INTUSSUSCEPTION OF STOMA FOLLOWING GASTRO-ENTEROSTOMY. PMID- 17864726 TI - EIGHT TOES ON ONE FOOT. PMID- 17864727 TI - EFFECTS OF SODIUM CITRATE ON BLOOD COAGULATION. PMID- 17864728 TI - THE TREATMENT OF CHRONIC EMPYEMA WHERE THE RECOGNIZED SURGICAL PROCEDURES HAVE FAILED TO PRODUCE OBLITERATION. PMID- 17864729 TI - PULMONARY FAT EMBOLISM. PMID- 17864730 TI - SURGICAL TREATMENT OF HEPATIC ABSCESS AND HYDATID CYSTS EVACUATING VIA BRONCHUS. PMID- 17864731 TI - TREATMENT OF FRACTURED CLAVICLES. PMID- 17864732 TI - COMPRESSION FRACTURES OF THE LOWER END OF THE RADIUS. PMID- 17864733 TI - ARTHROPLASTY OF THE ELBOW. PMID- 17864735 TI - IMMEDIATE OPERATION AS THE METHOD OF CHOICE IN THE TREATMENT OF FRACTURE OF THE NECK OF THE FEMUR. PMID- 17864734 TI - THE DIAGNOSIS AND TREATMENT OF INCOMPLETE EPIPHYSEAL FRACTURES AT THE HIP. PMID- 17864736 TI - SPRAINS OF THE RHOMBOIDEUS MINOR MUSCLE: A STUDY OF ONE HUNDRED AND FIFTY INJURIES OF THE SHOULDER GIRDLE. PMID- 17864737 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held April 3, 1922. PMID- 17864738 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held May 8, 1922. PMID- 17864739 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held April 26, 1922. PMID- 17864740 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held May 10, 1922. PMID- 17864741 TI - THE EFFICIENT TREATMENT OF ACUTE AND CHRONIC, SIMPLE, TRAUMATIC SYNOVITIS (HAEMARTHROSES AND HYDARTHROSES) BY REPEATED ASPIRATIONS AND IMMEDIATE, ACTIVE MOBILIZATIONS WITHOUT SPLINTING. PMID- 17864742 TI - A METASTASIZING MALIGNANT TUMOR OF THE THYROID GLAND. PMID- 17864743 TI - SUPPURATIVE OSTEOMYELITIS DUE TO THE COLON BACILLUS. PMID- 17864744 TI - THE TREATMENT OF CHRONIC EMPYEMA WHERE THE RECOGNIZED SURGICAL PROCEDURES HAVE FAILED TO PRODUCE OBLITERATION. PMID- 17864746 TI - ASEPTIC RESECTION OF INTESTINE: END-TO-END ANASTOMOSIS AND IMMEDIATE RESTORATION OF LUMEN BY USE OF SPECIAL APPLICATION OF REMOVABLE LOOPED LIGATURE. PMID- 17864745 TI - CHRONIC CATARRHAL CHOLECYSTITIS WITH LIPOID DEPOSIT. PMID- 17864747 TI - ASEPTIC TECHNIC FOR THE RESECTION OF INTESTINE: BLIND END-TO-END ANASTOMOSIS WITH THE RELEASE OF PURSE-STRING SUTURE AFTER THE ANASTOMOSIS IS COMPLETE. PMID- 17864749 TI - SOLID CARCINOMA OF THE OVARY. PMID- 17864748 TI - INVOLVEMENT OF THE LYMPH-NODES IN CARCINOMA OF THE RECTUM. PMID- 17864751 TI - SUBMAXILLARY SALIVARY CALCULUS. PMID- 17864750 TI - DOUBLE LIP. PMID- 17864752 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held March 22, 1922. PMID- 17864754 TI - PRESSURE AS A FACTOR IN SKIN GRAFTING. PMID- 17864753 TI - SECURING LARGE SKIN GRAFTS. PMID- 17864755 TI - DRAINAGE IN BLADDER CANCER. PMID- 17864756 TI - GONOCOCCUS IN ARM ABSCESS. PMID- 17864757 TI - CANCER OF THE LARYNX: IS IT PRECEDED BY A RECOGNIZABLE PRECANCEROUS CONDITION? PMID- 17864759 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 9, 1922: Stated Meeting Held October. PMID- 17864758 TI - BONE TUMORS, METASTASIS TO LUNGS FROM A PURE MYXOMA. PMID- 17864761 TI - Power Driven to-and-fro Saw. PMID- 17864760 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 11, 1922: Stated Meeting Held October. PMID- 17864762 TI - Operating Rooms and Body Warmth of Patients. PMID- 17864764 TI - The Abduction Treatment of Fracture of the Neck of the Femur. PMID- 17864763 TI - Question of Priority in Extirpation of the Gasserian Ganglion. PMID- 17864765 TI - Traumatic Pancreatitis. PMID- 17864767 TI - PERI-ARTERIAL SYMPATHECTOMY: AN EXPERIMENTAL STUDY. PMID- 17864766 TI - ARTERIAL DECORTICATION. PMID- 17864768 TI - ALUMINUM-POTASSIUM NITRATE IN THE TREATMENT OF SUPPURATIVE CONDITIONS, PARTICULARLY OSTEOMYELITIS. PMID- 17864769 TI - CHOLECYSTOSTOMY VERSUS CHOLECYSTECTOMY. PMID- 17864770 TI - CHOLELITHIASIS, CHOLECYSTITIS AND CHOLANGITIS. PMID- 17864771 TI - CERTAIN ASPECTS OF SURGERY OF THE GALL-BLADDER. PMID- 17864772 TI - REMOVAL OF A RETENTION CYST FROM THE LIVER. PMID- 17864773 TI - COLLOID CARCINOMA. PMID- 17864774 TI - THE REGENERATION OF THE MENINGES: THE DURA MATER. PMID- 17864775 TI - CHRONIC EMPYEMA: ITS ETIOLOGY, PATHOLOGY, DIAGNOSIS, COMPLICATIONS, TREATMENT AND FINAL RESULTS. PMID- 17864776 TI - INGUINAL HERNIA IN THE MALE: LATE RESULTS IN 978 TRACED CASES. PMID- 17864777 TI - IMPROVED TECHNIC FOR GASTRECTOMY AND GASTRO-ENTEROSTOMY. PMID- 17864778 TI - THE LIMITATIONS OF THE OCHSNER TREATMENT IN CERTAIN CASES OF SUPPURATIVE PERITONITIS. PMID- 17864779 TI - SPONTANEOUS INTRAPERITONEAL RUPTURE OF THE BLADDER. PMID- 17864780 TI - THE MECHANISM OF THE FORMATION OF URINARY CALCULI. PMID- 17864781 TI - SKIN GRAFTING BY EXACT PATTERN: A REPORT OF COSMETIC RESULTS OBTAINED WITHOUT THE EMPLOYMENT OF SUTURES. PMID- 17864782 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held October 25, 1922. PMID- 17864783 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held November 6, 1922. PMID- 17864784 TI - SPIRAL FRACTURES. PMID- 17864785 TI - HYPERTHYROIDISM WITH ASSOCIATED DIABETES MELLITUS. PMID- 17864786 TI - GASTRO-JEJUNOSTOMY FOR PERFORATED GASTRIC AND DUODENAL ULCERS. PMID- 17864787 TI - GENERAL PLASTIC SURGERY. PMID- 17864788 TI - THE TREATMENT OF ANTHRAX INFECTIONS. PMID- 17864789 TI - TREATMENT OF DIVERTICULUM OF THE OESOPHAGUS. PMID- 17864791 TI - PAPILLOMA AND ADENOMA OF GALL-BLADDER. PMID- 17864790 TI - THE METASTASIZING TENDENCY OF OESOPHAGUS CARCINOMA. PMID- 17864792 TI - WHITE BILE IN THE COMMON DUCT. PMID- 17864793 TI - THE SURGICAL TREATMENT OF CHRONIC ULCERATIVE COLITIS. PMID- 17864794 TI - MESENTERIC THROMBOSIS. PMID- 17864795 TI - SARCOMA OR EMBRYOMA OF THE KIDNEY IN INFANTS. PMID- 17864796 TI - SPONTANEOUS HAEMATOMA IN SARCOMA OF KIDNEY. PMID- 17864797 TI - URETERAL INJURIES DURING PELVIC OPERATIONS. PMID- 17864799 TI - RADICAL OPERATION FOR CHRONIC EMPYEMA. PMID- 17864798 TI - TYPHOIDAL OSTEOMYELITIS. PMID- 17864800 TI - TERATOID MIXED TUMORS OF THE BREAST: REPORT OF A CASE. PMID- 17864801 TI - RUPTURE OF THE LONG HEAD OF THE BICEPS FLEXOR CUBITI MUSCLE. PMID- 17864802 TI - THE VALUE AND LIMITATIONS OF BLOOD TRANSFUSION. PMID- 17864804 TI - ANEURISM OF THE THIGH. PMID- 17864803 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held November 8, 1922. PMID- 17864805 TI - LYMPHANGIOMA OF THE NECK. PMID- 17864807 TI - EMPYEMA THORACIS: ANALYSIS OF TWO HUNDRED AND FIFTY CASES TREATED AT THE CHILDREN'S HOSPITAL OF PHILADELPHIA. PMID- 17864806 TI - LIGATION OF INFERIOR THYROID ARTERY. PMID- 17864808 TI - THE EXPERIMENTAL PRODUCTION OF PEPTIC ULCER. PMID- 17864809 TI - THE RELATIONSHIP BETWEEN CERTAIN FORMS OF INTESTINAL OBSTRUCTION, CHRONIC PERITONITIS AND CHRONIC MULTIPLE SEROSITIS. PMID- 17864810 TI - GASTRO-COLIC FISTULA. PMID- 17864811 TI - SLIDING HERNIAS OF THE CAECUM AND APPENDIX IN CHILDREN. PMID- 17864812 TI - MASSIVE VENTRAL HERNIA WITH FECAL FISTULA. PMID- 17864813 TI - DOUBLE KIDNEY. PMID- 17864814 TI - SARCOMA OF THE UTERUS. PMID- 17864815 TI - SEPARATION OF THE UPPER EPIPHYSIS OF THE TIBIA. PMID- 17864816 TI - SPONDYLOLISTHESIS. PMID- 17864817 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held November 22, 1922. PMID- 17864818 TI - TRACTION APPARATUS FOR OPEN REDUCTION OF FRACTURES. PMID- 17864819 TI - ISCHAEMIC FAT NECROSIS. PMID- 17864820 TI - THE SIGNIFICANCE OF DIARRHOEA FOLLOWING ABDOMINAL OPERATIONS. PMID- 17864821 TI - DOUBLE KIDNEY. PMID- 17864822 TI - A METHOD FOR DETERMINING THE QUESTION OF DRAINAGE IN INTRA-ABDOMINAL INFECTION. PMID- 17864823 TI - REDUPLICATION OF THE URETER. PMID- 17864824 TI - A MODIFICATION OF THE OPERATION OF BUCKNALL FOR HYPOSPADIAS. PMID- 17864825 TI - BENIGN TUMORS OF THE STOMACH. PMID- 17864826 TI - GALL-BLADDER DISEASE IN CHILDHOOD. PMID- 17864827 TI - COMBINATION ILEUS, OR THE COINCIDENCE OF TWO INTESTINAL OCCLUSIONS. PMID- 17864829 TI - ANTERIOR DISLOCATION AT THE ELBOW JOINT. PMID- 17864828 TI - TRANSPOSITION OF THE RECTUS MUSCLE AND THE UTILIZATION OF THE EXTERNAL OBLIQUE APONEUROSIS IN THE RADICAL CURE OF INGUINAL HERNIA. PMID- 17864831 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held December 4, 1922. PMID- 17864830 TI - CARDIOSPASM IN THE AGED. PMID- 17864832 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held December 13, 1922. PMID- 17864833 TI - THE URETER VERSUS THE APPENDIX IN RIGHT-SIDED ABDOMINAL LESIONS. PMID- 17864834 TI - SURGICAL RELATIONS OF THE SYMPATHETIC NERVOUS SYSTEM. PMID- 17864835 TI - THE SURGICAL TREATMENT OF UNILATERAL PULMONARY TUBERCULOSIS. PMID- 17864836 TI - TUBERCULOSIS OF THE BREAST. PMID- 17864837 TI - TUMORS OF THE BREAST-INNOCENT AND MALIGNANT. PMID- 17864838 TI - RANULA. PMID- 17864839 TI - FACTORS OF SAFETY IN THYROID SURGERY. PMID- 17864840 TI - PATHOLOGICAL FRACTURE OF THE NECK OF THE FEMUR, DUE TO THYROID METASTASIS. PMID- 17864841 TI - INVOLVEMENT OF THE LYMPH GLANDS IN CANCER OF THE CAECUM. PMID- 17864842 TI - CANCER OF THE RECTUM AND SIGMOID IN CHILDHOOD AND ADOLESCENCE. PMID- 17864843 TI - SARCOMA OF THE OMENTUM. PMID- 17864844 TI - CONGENITAL DIAPHRAGMATIC HERNIA. PMID- 17864845 TI - NON-OPERATIVE TREATMENT OF DISPLACED SEMILUNAR CARTILAGES OF THE KNEE-JOINT. PMID- 17864846 TI - FRACTURES OF THE FEMUR IN CHILDREN: TREATMENT AND END RESULTS IN 268 CASES. PMID- 17864848 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held February 14, 1923. PMID- 17864847 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY AND OF THE PHILADELPHIA ACADEMY OF SURGERY Joint Meeting Held January 24, 1923. PMID- 17864849 TI - TREATMENT OF TRAUMATIC SYNOVITIS. PMID- 17864850 TI - GONOCOCCUS MYOSITIS. PMID- 17864851 TI - PREVENTION OF FAT NECROSIS IN INCISIONS. PMID- 17864852 TI - ALUMINUM POTASSIUM NITRATE IN OSTEOMYELITIS. PMID- 17864854 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 28, 1923: Stated Meeting Held February. PMID- 17864853 TI - FATAL ANAPHYLAXIS FOLLOWING BLOOD TRANSFUSION. PMID- 17864855 TI - Lympho-sarcoma of the Tonsils with Cervical Metastasis. PMID- 17864856 TI - Acute Intestinal Obstruction. PMID- 17864857 TI - Diet after Gastro-enterostomy. PMID- 17864858 TI - Osteomyelitis of the Spine. PMID- 17864859 TI - The Question of Intra-abdominal Drainage. PMID- 17864861 TI - TRAUMATIC LESIONS OF THE HEAD. PMID- 17864860 TI - MULTIPLE MYELOMA OF THE PLASMA-CELL TYPE. PMID- 17864862 TI - OPERATIONS FOR DIAPHRAGMATIC HERNIA. PMID- 17864864 TI - HAEMANGIOMA OF THE INTESTINE. PMID- 17864863 TI - PERFORATION IN UTERO OF A GASTRIC ULCER. PMID- 17864865 TI - A MODIFIED INGUINAL HERNIOPLASTY. PMID- 17864867 TI - INTRACERVICAL ENUCLEATION. PMID- 17864866 TI - PLEURAL EPILEPSY. PMID- 17864868 TI - SURGERY OF THE ECTOPIC KIDNEY. PMID- 17864869 TI - METAL PLATES IN FRACTURES OF THE LONG BONES. PMID- 17864870 TI - WOUND OF FEMORAL ARTERY AND VEIN. PMID- 17864871 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 8, 1923: Stated Meeting Held January. PMID- 17864872 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 5, 1923: Stated Meeting Held February. PMID- 17864873 TI - REPAIR OF THE COMMON BILE DUCT. PMID- 17864874 TI - A QUESTION OF SIZE. PMID- 17864875 TI - SURGERY OF THE THYROID AND ITS MORTALITY. PMID- 17864876 TI - THE MANY-STAGE OPERATION FOR GOITRE. PMID- 17864877 TI - EVENTRATION OF THE DIAPHRAGM. PMID- 17864878 TI - CARDIOPLASTY FOR CARDIOSPASM. PMID- 17864880 TI - PANCREATIC ASTHENIA AS A POST-OPERATIVE COMPLICATION IN PATIENTS WITH LESIONS OF THE PANCREAS. PMID- 17864879 TI - AN OPERATION FOR THE RELIEF OF CARDIOSPASM ASSOCIATED WITH DILATATION AND TORTUOSITY OF THE OESOPHAGUS. PMID- 17864881 TI - SPLENECTOMY IN HEMORRHAGIC PURPURA: IDIOPATHIC PURPURA, ESSENTIAL THROMBOPENIE (FRANK). PURPURA HEMORRHAGIC PROTOPATHIQUE (HAYEM). PMID- 17864882 TI - SPECIAL POINTS IN GALL-BLADDER SURGERY. PMID- 17864883 TI - THE MORTALITY FOLLOWING OPERATIONS ON THE LIVER, PANCREAS, AND BILIARY PASSAGES: A STATISTICAL STUDY. PMID- 17864884 TI - FURTHER OBSERVATIONS ON THE USE OF THE CAUTERY IN PEPTIC ULCER. PMID- 17864885 TI - CANCER OF THE COLON. PMID- 17864886 TI - EMBRYOMA OF THE KIDNEY. PMID- 17864887 TI - CERTAIN FEATURES OF RENAL CALCULUS. PMID- 17864888 TI - OSSIFICATION IN KIDNEY STONES ATTACHED TO THE RENAL PELVIS. PMID- 17864889 TI - THE OPERATION OF CHOICE IN THE SURGERY OF THE KIDNEY. PMID- 17864890 TI - CARCINOMA OF THE BLADDER. PMID- 17864891 TI - PATHOLOGICAL CHANGES, OCCURRING IN THE SPINAL CORD, FOLLOWING FRACTURE DISLOCATION OF THE VERTEBRAE. PMID- 17864892 TI - ACTINOMYCOSIS. PMID- 17864894 TI - END RESULTS OF ARTERIAL TRANSPLANTS. PMID- 17864893 TI - HERNIA THROUGH THE CONJOINED TENDON OR HERNIA OF THE LINEA SEMILUNARIS. PMID- 17864895 TI - RELATION OF SURGERY TO THE VASCULAR SYMPATHETIC SYSTEM. PMID- 17864897 TI - THE OPERATIVE CURABILITY OF CARCINOMA OF THE STOMACH. PMID- 17864896 TI - ANTHRAX AND ITS TREATMENT. PMID- 17864898 TI - ACUTE PERFORATION OF DUODENAL ULCER. PMID- 17864899 TI - ACUTE INTUSSUSCEPTION IN INFANTS. PMID- 17864900 TI - EXPERIMENTAL STUDY UPON THE USE OF INTRA-ABDOMINAL INJECTIONS OF HYPERTONIC GLUCOSE SOLUTION IN THE TREATMENT OF PERITONITIS. PMID- 17864902 TI - END-RESULTS IN MALIGNANT DISEASE OF THE TESTIS. PMID- 17864901 TI - THE INFLUENCE OF HEMORRHAGE ON THE MORTALITY IN GUNSHOT WOUNDS AND OTHER INJURIES OF THE ABDOMEN-WITH AN ANALYSIS OF 69 CASES. PMID- 17864903 TI - EMPYEMA OF THE URETERAL STUMP FOLLOWING INCOMPLETE URETERECTOMY. PMID- 17864905 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held March 5, 1923. PMID- 17864904 TI - RUPTURE OF TENDON OF EXTENSOR LONGUS POLLICIS FOLLOWING A COLLES FRACTURE. PMID- 17864906 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held March 14, 1923. PMID- 17864907 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held March 28, 1923. PMID- 17864908 TI - MANAGEMENT OF INJURIES TO THE CRANIUM AND ITS CONTENTS: WITH SPECIAL REFERENCE TO CEREBROSPINAL FLUID PRESSURE DETERMINATIONS. PMID- 17864910 TI - NOTE ON THE PATHOLOGY AND SURGICAL TREATMENT OF LEUKOKERATOSIS LINGUAE. PMID- 17864909 TI - CANCER OF THE TONGUE. PMID- 17864911 TI - LEUCOPLAKIA BUCCALIS. PMID- 17864912 TI - ABSCESS OF THE TONGUE. PMID- 17864913 TI - INTERCOSTAL THORACOPUNCTURE FOR THE REMOVAL OF PENETRATING PROJECTILES IN THE LUNG. PMID- 17864914 TI - RESECTION OF STOMACH FOR CHRONIC GASTRIC AND DUODENAL ULCER. PMID- 17864915 TI - RECURRENCE OF INGUINAL HERNIA AFTER OPERATIVE TREATMENT. PMID- 17864916 TI - TREATMENT OF WEBBED FINGERS CONGENITAL OR ACQUIRED. PMID- 17864917 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held April 2, 1923. PMID- 17864918 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held April 11, 1923. PMID- 17864919 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held April 25, 1923. PMID- 17864920 TI - PNEUMOVENTRICLE OF THE CEREBRUM FOLLOWING FRACTURE OF THE SKULL. PMID- 17864921 TI - POST-OPERATIVE INFECTIVE PAROTIDITIS. PMID- 17864922 TI - THE IMPORTANCE IN SURGERY OF THE THYROID GLAND OF THE CORRECT DIFFERENTIAL DIAGNOSIS OF THYROID DISEASES. PMID- 17864923 TI - PRIMARY SARCOMA OF THE OESOPHAGUS. PMID- 17864924 TI - TREATMENT OF HOUR-GLASS STOMACH BY DOUBLE GASTRO-ENTEROSTOMY. PMID- 17864925 TI - HYPERCHOLESTEROLEMIA: REPORT OF A CASE TREATED BY BILE DRAINAGE. PMID- 17864926 TI - THE MELTZER-LYONS TEST IN THE DIAGNOSIS OF GALL-BLADDER DISEASE. PMID- 17864927 TI - CHRONIC CHOLECYSTITIS WITHOUT STONE. PMID- 17864928 TI - DRAINAGE OF THE COMMON BILE DUCT: A NOTE ON A METHOD OF REGULATING THE EXTERNAL DRAINAGE OF BILE. PMID- 17864929 TI - CALCAREOUS CHANGES OF THE GALL-BLADDER WALL. PMID- 17864930 TI - ANEURISM OF THE RENAL ARTERY: AN ANALYSIS OF ALL CASES IN THE LITERATURE WITH A REPORT OF A CASE AND A DISSERTATION ON THE ETIOLOGY, PATHOLOGY, SYMPTOMS, DIAGNOSIS, PROGNOSIS, AND TREATMENT OF THIS CONDITION. PMID- 17864931 TI - THE TECHNIC OF RENAL AND URETERAL SURGERY. PMID- 17864932 TI - A CONSERVATIVE TREATMENT OF CARBUNCLES. PMID- 17864934 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held May 7, 1923. PMID- 17864933 TI - DIAPHRAGMATIC HERNIA. PMID- 17864935 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held May 9, 1923. PMID- 17864936 TI - GASTRO-COLIC FISTULA. PMID- 17864937 TI - A GRIDIRON AND A HALF-GRIDIRON INCISION IN OPERATIONS ON THE BILIARY TRACT. PMID- 17864938 TI - EFFECT OF PRE-OPERATIVE DIGITALIZATION IN REDUCING POST-OPERATIVE COMPLICATIONS. PMID- 17864939 TI - CARDIORRHAPHY IN ACUTE INJURIES: WITH REPORT OF TWO CASES AND A TABLE OF REPORTED CASES. PMID- 17864940 TI - EMPYEMA OF THE PLEURAL CAVITY. PMID- 17864941 TI - EXTERNAL DUODENAL FISTULAE. PMID- 17864942 TI - EXTENSIVE RESECTION OF THE SMALL INTESTINE: REPORT OF RECOVERY AFTER RESECTION OF FIFTEEN FEET OF SMALL INTESTINE AND HYSTERECTOMY. PMID- 17864943 TI - THE RELATION OF CIRRHOSIS OF MESENTERY AND SUBPERITONEAL LIPOMATOSIS TO ALCOHOL AND WORK. PMID- 17864944 TI - INTESTINAL OBSTRUCTION: AN EXPERIMENTAL STUDY OF THE THERAPEUTIC VALUE OF THE ADMINISTRATION OF SODIUM CHLORIDE. PMID- 17864945 TI - MALIGNANT TUMORS OF THE TESTICLE IN CHILDREN. PMID- 17864946 TI - ACUTE DEFERENTITIS AND FUNICULITIS. PMID- 17864947 TI - TRANSPUBIC REMOVAL OF THE PROSTATE FOR CARCINOMA. PMID- 17864948 TI - THE CONTROL OF HEMORRHAGE FOLLOWING PROSTATECTOMY. PMID- 17864949 TI - FRACTURE OF THE ACETABULUM WITH CENTRAL LUXATION OF THE HIP. PMID- 17864950 TI - SCLERODERMA WITH GANGRENE OF FINGERS: REPORT OF TWO CASES. PMID- 17864951 TI - THE DISABILITIES OF THE HAND AND THEIR PHYSIOLOGICAL TREATMENT. PMID- 17864952 TI - GIANT CELL SARCOMA OF THE FEMUR (EPULIS TYPE) WITH METASTASIS IN THE FEMORAL VEIN. PMID- 17864953 TI - SURGICAL SIGNIFICANCE OF ABDOMINAL PAIN. PMID- 17864955 TI - UTERUS DIDELPHYS: NOTES ON ITS DEVELOPMENTAL ETIOLOGY AND ITS CLINICAL SIGNIFICANCE. PMID- 17864954 TI - ASEPTIC TECHNIC FOR THE RESECTION OF INTESTINE: REPORT OF THREE ADDITIONAL CASES. PMID- 17864956 TI - ENCYSTED FOREIGN BODIES. PMID- 17864957 TI - SACRAL ANAESTHESIA. PMID- 17864958 TI - INSTRUMENTARIUM FOR LOCAL ANAESTHESIA. PMID- 17864960 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held October 10, 1923. PMID- 17864959 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held October 1, 1923. PMID- 17864961 TI - CRIPPLED JOINTS AND FLAT FEET. PMID- 17864962 TI - THE TOXINS OF PREGNANCY AND GALL-BLADDER DISEASE IN THE FOETUS. PMID- 17864963 TI - ENCAPSULATED ADENOMATA OF THE THYROID: IMPROVED TECHNIC FOR THEIR REMOVAL. PMID- 17864964 TI - THE BACTERIOLOGY OF EXTIRPATED TONSILS AND ITS RELATION TO EPIDEMIC TONSILLITIS. PMID- 17864965 TI - A STUDY ON FOCAL INFECTION AND ELECTIVE LOCALIZATION IN ULCER OF THE STOMACH AND IN ARTHRITIS. PMID- 17864966 TI - GUMMA OF THE BREAST; ITS DIFFERENTIAL DIAGNOSIS FROM CARCINOMA. PMID- 17864967 TI - THE LIVER AND ITS RELATION TO CHRONIC ABDOMINAL INFECTION. PMID- 17864968 TI - A METHOD OF RECONSTRUCTING AN ANOMALOUS HEPATIC DUCT INJURED AT OPERATION. PMID- 17864969 TI - RUPTURE OF THE SPLEEN: REPORT OF TWENTY CASES OBSERVED IN CHINA. PMID- 17864971 TI - ACUTE PERFORATED ULCER OF THE STOMACH AND DUODENUM. PMID- 17864970 TI - ENDOTHERMY IN THE TREATMENT OF ACCESSIBLE NEOPLASTIC DISEASES. PMID- 17864972 TI - THE TREATMENT OF PARALYSIS OF THE RECURRENT LARYNGEAL NERVE BY NERVE ANASTOMOSIS. PMID- 17864973 TI - BENIGN TUMORS OF THE BREAST. ENCAPSULATED ADENOMA: A BRIEF SUMMARY OF THEIR CLINICAL AND PATHOLOGICAL FEATURES. PMID- 17864974 TI - SOME OBSERVATIONS ON THE TREATMENT OF FRACTURE OF THE SKULL: REPORT OF ONE HUNDRED CASES FROM THE PENNSYLVANIA HOSPITAL. PMID- 17864975 TI - CONGENITAL SOLITARY KIDNEY. PMID- 17864976 TI - PYLORECTOMY FOLLOWED BY KOCHER'S METHOD OF GASTRODUODENOSTOMY IN CERTAIN CASES OF CARCINOMA OF THE STOMACH. PMID- 17864977 TI - CARCINOMA OF THE DUODENUM. PMID- 17864979 TI - FASCIA TO FASCIA IN INGUINAL HERNIA OPERATIONS. PMID- 17864978 TI - CHRONIC PRIMARY INTUSSUSCEPTION IN YOUNG CHILDREN. PMID- 17864980 TI - HISTOLOGIC EVIDENCES OF INFLAMMATION IN THE SACS OF CERTAIN INGUINAL HERNIAE. PMID- 17864981 TI - CHRONIC RETENTION OF URINE IN YOUNG BOYS DUE TO OBSTRUCTION AT THE NECK OF THE BLADDER. PMID- 17864982 TI - LOCOMOTION AFTER IMPACTED FRACTURE OF THE NECK OF THE FEMUR. PMID- 17864983 TI - THE PROGNOSIS IN EPIPHYSEAL LINE FRACTURES. PMID- 17864984 TI - SPINAL ANAESTHESIA. PMID- 17864985 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held November 5, 1923. PMID- 17864986 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held October 24, 1923. PMID- 17864987 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held November 14, 1923. PMID- 17864988 TI - PROGNOSIS IN GIANT-CELL SARCOMA OF THE LONG BONES: BASED UPON THE END-RESULTS IN A SERIES OF 50 CASES. PMID- 17864989 TI - ADAMANTINE EPITHELIOMA OF THE LOWER JAW: CLINICAL REPORT OF TWO UNUSUAL CASES. PMID- 17864990 TI - THE MATAS OPERATION FOR ANEURISM: REPORT OF PERSONAL CASES. PMID- 17864991 TI - AN IMPROVED METHOD OF REMOVING HERNIA FROM WITHIN. PMID- 17864992 TI - THE INFLUENCE OF HEMORRHAGE ON THE MORTALITY IN GUNSHOT WOUNDS AND OTHER INJURIES OF THE ABDOMEN: A SUPPLEMENTARY REPORT WITH ANALYSIS OF 127 CASES. PMID- 17864993 TI - PARTIAL GASTRECTOMY FOR GASTROJEJUNAL ULCER. PMID- 17864994 TI - SURGERY OF RENAL TUBERCULOSIS. PMID- 17864995 TI - PILONIDAL SINUS: COCCYGEAL FISTULA. PMID- 17864996 TI - COMPLETE OUTWARD DISLOCATION OF THE PATELLA. PMID- 17864998 TI - RECENT CONTROVERSIAL QUESTIONS IN GALL-BLADDER SURGERY. PMID- 17864997 TI - PRIMARY PERITONITIS. PMID- 17865000 TI - AN IMPROVED ABDOMINAL RETRACTOR. PMID- 17864999 TI - ANAESTHESIA OF THE SPLANCHNIC NERVE IN ABDOMINAL OPERATIONS. PMID- 17865001 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held November 28, 1923. PMID- 17865002 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held December 12, 1923. PMID- 17865003 TI - A PLAN OF MANAGEMENT OF CRANIAL INJURIES BASED ON A NEW GROUPING OF SUCH INJURIES. PMID- 17865004 TI - ARTHROPLASTY UPON THE TEMPOROMANDIBULAR JOINT. PMID- 17865005 TI - MALIGNANT TUMORS OF THE THYROID. PMID- 17865006 TI - EXOPHTHALMIC GOITRE RESULTING IN BLINDNESS FROM CORNEAL ULCERS. PMID- 17865007 TI - A CONTRIBUTION TO THE STUDY OF FISTULAE AND CYSTS OF THE NECK. PMID- 17865008 TI - POST-OPERATIVE PULMONARY COMPLICATIONS. PMID- 17865009 TI - ANGINA PECTORIS AND SURGICAL CONDITIONS OF THE ABDOMEN. PMID- 17865010 TI - NON-CALCULOUS INTERMITTENT BILIARY OBSTRUCTION FOLLOWING CHOLECYSTECTOMY. PMID- 17865011 TI - ACUTE APPENDICITIS IN CHILDHOOD: A STUDY OF 145 CASES OBSERVED AT BELLEVUE HOSPITAL OF NEW YORK CITY. PMID- 17865012 TI - FRACTURE OF THE ANTERIOR SUPERIOR SPINE OF THE ILIUM BY MUSCULAR VIOLENCE. PMID- 17865014 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held December 3, 1923. PMID- 17865013 TI - PROGNOSIS IN GIANT-CELL SARCOMA OF THE LONG BONES: BASED UPON THE END-RESULTS IN A SERIES OF 50 CASES. PMID- 17865015 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held January 7, 1924. PMID- 17865016 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held January 9, 1924. PMID- 17865017 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held January 23, 1924. PMID- 17865018 TI - GASTRO-JEJUNO-COLIC FISTULA. PMID- 17865019 TI - GANGRENE OF THE BREAST COMPLICATING DIABETES. PMID- 17865021 TI - PNEUMATIC INJECTORS IN LOCAL ANAESTHESIA. PMID- 17865020 TI - PROLONGED WEARING OF A PLASTER BANDAGE WITHOUT REMOVAL. PMID- 17865022 TI - THE PNEUMATIC INJECTOR FOR LOCAL ANAESTHESIA. PMID- 17865023 TI - THE USE OF THE CAUTERY IN THE TREATMENT OF ABSCESS OF THE LUNG. PMID- 17865024 TI - THE CONTINUED INTRAVENOUS "DRIP": WITH REMARKS ON THE VALUE OF CONTINUED GASTRIC DRAINAGE AND IRRIGATION BY NASAL INTUBATION WITH A GASTRODUODENAL TUBE (JUTTE) IN SURGICAL PRACTICE. PMID- 17865025 TI - SOME PROBLEMS OF JAUNDICE AND THEIR SIGNIFICANCE IN SURGERY. PMID- 17865027 TI - TUMORS OF THE MEDIASTINUM IN CHILDREN. PMID- 17865026 TI - INTRATHORACIC TUMORS: EXPERIENCES WITH EIGHT CASES OF TUMOR OF THE THORACIC WALL PLEURA AND MEDIASTINUM. PMID- 17865028 TI - THE TREATMENT OF SUPPURATIVE PERITONITIS. PMID- 17865029 TI - THE VALUE OF THE RONTGEN EXAMINATION IN THE EARLY DIAGNOSIS OF POST-OPERATIVE ILEUS. PMID- 17865030 TI - SOME SURGICAL RELATIONS OF CHOLECYSTITIS. PMID- 17865032 TI - TRANSVERSE INCISION AND DEPENDENT DRAINAGE IN APPENDICITIS. PMID- 17865031 TI - AMOEBIC LIVER ABSCESS: WITH A REPORT OF TWO CASES OCCURRING IN CONNECTICUT. PMID- 17865033 TI - RECURRING HERNIA OF THE DIAPHRAGM. PMID- 17865034 TI - A METHOD OF REPAIRING INGUINAL HERNIA WITH LIVING SUTURES TAKEN FROM THE EXTERNAL OBLIQUE TENDON. PMID- 17865036 TI - STRICTURE OF THE FEMALE URETHRA. PMID- 17865035 TI - CYSTS OF THE WOLFFIAN BODY. PMID- 17865037 TI - WOUNDS OF THE LOWER EXTREMITY COMMUNICATING WITH A FRACTURE OR JOINT. PMID- 17865038 TI - SIMULTANEOUS DISLOCATION OF BOTH SHOULDER JOINTS. PMID- 17865039 TI - THE PRE-OPERATIVE PREPARATION OF HANDICAPPED SURGICAL PATIENTS. PMID- 17865040 TI - GAS GANGRENE. PMID- 17865041 TI - THE INCIDENCE OF POST-OPERATIVE CATHETERIZATION IN THE JOHNS HOPKINS HOSPITAL. PMID- 17865042 TI - CONCLUSIONS BASED ON A STUDY OF FOUR THOUSAND CASES OF GOITRE. PMID- 17865043 TI - SUBDIAPHRAGMATIC ABSCESS AND ACCUMULATIONS OF FLUID. PMID- 17865044 TI - REVIEW OF FIVE THOUSAND FOUR HUNDRED AND EIGHTY-EIGHT APPENDECTOMIES PERFORMED AT THE LANKENAU HOSPITAL OF PHILADELPHIA. PMID- 17865045 TI - A REPORT ON 262 CONSECUTIVE CASES OF APPENDICITIS. PMID- 17865046 TI - LYMPHOID HYPERPLASIA OF THE APPENDIX IN CHILDREN; ITS RELATION TO RECURRENT APPENDICITIS. PMID- 17865047 TI - TUMOR OF THE OVARY WITH TWISTED PEDICLE, OCCURRING IN A CHILD TWO AND A HALF YEARS OF AGE. PMID- 17865048 TI - ANEURISMS OF THE ILIAC AND FEMORAL ARTERIES. PMID- 17865049 TI - COMBINED EXTIRPATION AND OBLITERATION IN THE TREATMENT OF VARICOSE VEINS. PMID- 17865050 TI - VALUE OF PRELIMINARY CIRCULAR CONSTRICTION BY RUBBER TUBE IN CERTAIN CASES REQUIRING AMPUTATION. PMID- 17865051 TI - LACK OF OPERATIVE INDICATIONS IN ASTHMA AND OTHER FORMS OF ALLERGY. PMID- 17865052 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 4, 1924: Stated Meeting Held February. PMID- 17865053 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 13, 1924: Stated Meeting Held February. PMID- 17865054 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 27, 1924: Stated Meeting Held February. PMID- 17865055 TI - Traumatic Avulsion of the Scapula. PMID- 17865056 TI - Gall-bladder Disease in Youth. PMID- 17865057 TI - INTRACRANIAL ARTERIO-VENOUS ANEURISM OR PULSATING EXOPHTHALMOS. PMID- 17865058 TI - FRACTURES ABOUT THE UPPER END OF THE HUMERUS. PMID- 17865060 TI - SYSTEMIC BLASTOMYCOSIS (OIDIOMYCOSIS). PMID- 17865059 TI - IDIOPATHIC OSTEOPSATHYROSIS: FRAGILITAS OSSIUM. PMID- 17865061 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 26, 1924: Joint Meeting with the Philadelphia Academy of Surgery Held March. PMID- 17865062 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 26, 1924: Stated Meeting Held March. PMID- 17865063 TI - CHRONIC PRODUCTIVE THYROIDITIS. PMID- 17865065 TI - THE PREVENTION OF ACUTE INESTINAL OBSTRUCTION: ANALYSIS OF ONE HUNDRED CASES. PMID- 17865064 TI - THE PRESENT STATUS OF THE SURGICAL TREATMENT OF CHRONIC DUODENAL AND GASTRIC ULCER. PMID- 17865066 TI - THE TREATMENT OF ACUTE MECHANICAL INTESTINAL OBSTRUCTION BY HIGH TEMPORARY JEJUNOSTOMY. PMID- 17865067 TI - PERFORATED GUNSHOT AND STAB WOUNDS OF THE ABDOMEN: TREATED AT THE GOUVERNEUR HOSPITAL OF NEW YORK. PMID- 17865068 TI - APPENDICEAL FECAL FISTULA. PMID- 17865070 TI - CO-EXISTENT NEPHROLITHIASIS AND URETEROLITHIASIS ON OPPOSITE SIDES. PMID- 17865069 TI - FURTHER STUDY OF CYSTS OF THE SPLEEN. PMID- 17865071 TI - KNEE-JOINT INJURIES AND THEIR MANAGEMENT. PMID- 17865072 TI - ARTHROPLASTY OF THE KNEE. PMID- 17865073 TI - THE INDUCTION OF SPLANCHNIC ANALGESIA: FROM A CLINICAL AND ANATOMICAL STANDPOINT. PMID- 17865074 TI - SUBLINGUAL FIBROMA. PMID- 17865076 TI - POST-OPERATIVE STRICTURE OF THE COMMON BILE DUCT. PMID- 17865075 TI - ACUTE PANCREATITIS. PMID- 17865077 TI - CHRONIC PARTIAL INTESTINAL OBSTRUCTION IN AN ADULT DUE TO ARRESTED DEVELOPMENT OF THE LARGE BOWEL. PMID- 17865078 TI - HEMORRHAGIC ULCER OF MECKEL'S DIVERTICULUM. PMID- 17865079 TI - A METHOD OF HERNIOTOMY UTILIZING ONLY WHITE FASCIA. PMID- 17865080 TI - THE JACK-KNIFE POSITION FOR PATIENTS AFTER OPERATIONS FOR ABDOMINAL HERNIA. PMID- 17865081 TI - THREE THOUSAND CONSECUTIVE HERNIOTOMIES: WITH SPECIAL REFERENCE TO RECURRENCE, BASED ON EIGHT HUNDRED AND THIRTY SEVEN FOLLOWED CASES. PMID- 17865082 TI - THE SURGICAL ASPECTS OF XANTHOMA TUMORS. PMID- 17865083 TI - EFFECTS OF THE INTRAMUSCULAR INJECTION OF SODIUM CITRATE UPON BLEEDING. PMID- 17865084 TI - INTRACRANIAL ARTERIO-VENOUS ANEURISM OR PULSATING EXOPHTHALMOS. PMID- 17865085 TI - A BIPOLAR THEORY OF THE NATURE OF CANCER: PRESIDENTIAL ADDRESS, AMERICAN SURGICAL ASSOCIATION, APRIL 17, 1924. PMID- 17865086 TI - THE FULL THICKNESS SKIN GRAFT. PMID- 17865087 TI - ENDOANEURISMORRHAPHY: PERSONAL EXPERIENCE IN 21 CASES. PMID- 17865088 TI - CIRSOID ANEURISM OF THE SCALP: WITH THE REPORT OF AN ADVANCED CASE. PMID- 17865090 TI - ANEURISM OF THE PALMAR ARCHES: WITH A REPORT OF AN ANEURISM OF THE DEEP ARCH CURED BY EXCISION. PMID- 17865089 TI - ANEURISM OF THE INTERNAL MAMMARY ARTERY. PMID- 17865091 TI - THE INCIDENCE OF CONGENITAL CLEFTS OF THE LIP AND PALATE. PMID- 17865093 TI - END RESULTS IN SOME CONDITIONS ASSOCIATED WITH OR POSSIBLY CAUSED BY GOITRE. PMID- 17865092 TI - OESOPHAGOTOMY FOR FOREIGN BODIES IN THE OESOPHAGUS. PMID- 17865094 TI - END RESULTS OF GOITRE OPERATIONS. PMID- 17865095 TI - REPORT OF THE RESULTS OF OPERATION ON A GROUP OF 150 CASES OF GOITRE. PMID- 17865097 TI - THE SURGICAL TREATMENT OF HEPATIC CIRRHOSES. PMID- 17865096 TI - A REPORT OF 87 PRIMARY OPERABLE CASES OF CARCINOMA OF THE BREAST ADMITTED TO THE NEW YORK HOSPITAL PRIOR TO APRIL 1, 1919. PMID- 17865099 TI - SURGERY OF THE RIGHT HALF OF THE COLON. PMID- 17865098 TI - DIVERTICULITIS OF THE COLON. PMID- 17865100 TI - CARCINOMA OF THE COLON. PMID- 17865102 TI - RONTGENOLOGICAL VISUALIZATION OF THE GALL-BLADDER BY THE INTRAVENOUS INJECTION OF TETRABROMPHENOLPHTHALEIN. PMID- 17865101 TI - MULTIPLE PRIMARY MALIGNANT FOCI IN CANCER OF THE COLON. PMID- 17865103 TI - CLOSURE OF ARTIFICIAL ANUS OF EIGHT YEARS' DURATION, WITH SOME REMARKS ON THE QUESTION OF INTESTINAL ANASTOMOSIS. PMID- 17865104 TI - THE EFFECT OF PRESSURE ON ARTICULAR SURFACES IN PYOGENIC AND TUBERCULOUS ARTHRITIDES AND ITS BEARING ON TREATMENT. PMID- 17865105 TI - ENTEROSTOMY AS A THERAPEUTIC AND DIAGNOSTIC MEASURE. PMID- 17865106 TI - INTRA-ABDOMINAL RUPTURE OF INTESTINE FOLLOWING STRANGULATED FEMORAL HERNIA. PMID- 17865107 TI - THE ADDITIONAL POSTERIOR INCISION IN CERTAIN CASES OF OPERATION FOR THE INFLAMED RETROCAECAL APPENDIX. PMID- 17865108 TI - AN EXPERIMENTAL CONSIDERATION OF THE INFECTION OF PERMANENT HYDRONEPHROSES. PMID- 17865109 TI - THE FATE OF THE FRACTURED CARPAL NAVICULAR. PMID- 17865110 TI - THE REGENERATION OF THE MENINGES. PMID- 17865111 TI - THE TOXICITY AND RATE OF EXCRETION OF CALCIUM CHLORID FROM THE BLOOD STREAM. PMID- 17865112 TI - CANCER OF THE THYROID. PMID- 17865114 TI - LATE RESULTS OF SPLENECTOMY FOR TRAUMATIC RUPTURE OF THE SPLEEN. PMID- 17865113 TI - RESUSCITATION BY DIRECT MASSAGE OF THE HEART IN CARDIAC ARREST. PMID- 17865116 TI - PAPILLARY EPITHELIOMA OF KIDNEY PELVIS. PMID- 17865115 TI - MALIGNANT TUMORS OF THE KIDNEY IN CHILDREN. PMID- 17865118 TI - SURGICAL TRAUMA OF THE RECURRENT LARYNGEAL NERVE WITH RESTORATION OF FUNCTION. PMID- 17865117 TI - SQUAMOUS-CELL TUMORS OF THE RENAL PELVIS. PMID- 17865120 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held May 5, 1924. PMID- 17865119 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held April 7, 1924. PMID- 17865121 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held April 9, 1924. PMID- 17865122 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held April 23, 1924. PMID- 17865123 TI - THE DIAGNOSTIC VALUE AND INTERPRETATION OF CEREBRO-SPINAL DETERMINATIONS. PMID- 17865124 TI - THE MECHANISM OF POST-OPERATIVE HEMORRHAGE. PMID- 17865125 TI - FRACTURE OF THE LARYNX. PMID- 17865126 TI - TRAUMATIC FAT NECROSIS OF THE FEMALE BREAST AND ITS DIFFERENTIATION FROM CARCINOMA. PMID- 17865127 TI - THE NEUROTIC OR IRRITABLE ABDOMEN. PMID- 17865129 TI - LYMPHO-SARCOMA OF THE SMALL INTESTINES. PMID- 17865128 TI - STUDIES IN BILIARY TRACT SURGERY: A SURVEY OF 130 CONSECUTIVE SURGICAL CASES. PMID- 17865130 TI - URETERO-PYELOGRAPHY: A CRITIQUE ON ITS USE AS A DIAGNOSTIC PROCEDURE. PMID- 17865131 TI - CONGENITAL PERINEAL TESTICLE. PMID- 17865132 TI - BONE REGENERATION FOLLOWING CHRONIC SUPPURATIVE OSTEITIS OF THE DISTAL PHALANX. PMID- 17865133 TI - ERRORS IN THE X-RAY DIAGNOSIS OF OSTEOGENIC SARCOMA: REPORT OF TWO CASES WITH AUTOPSY FINDINGS. PMID- 17865135 TI - ADOLESCENT COXA VARA. PMID- 17865134 TI - SACRAL NERVE BLOCK ANAESTHESIA: THE ANATOMY INVOLVED, TECHNIC, AND CLINICAL APPLICATION. PMID- 17865136 TI - THE RECONSTRUCTION OPERATION FOR ARTHRITIS DEFORMANS OF THE HIP-JOINT. PMID- 17865137 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held May 14, 1924. PMID- 17865138 TI - NATURE'S CURE OF CHOLECYSTITIS. PMID- 17865139 TI - ARTERIOVENOUS ANEURISM: CLINICAL EVIDENCE CORRELATING SIZE OF FISTULA WITH CHANGES IN THE HEART AND PROXIMAL VESSELS. PMID- 17865140 TI - BONE TUMORS. MYXOMA: SECOND PAPER WITH REPORT OF THREE NEW CASES. PMID- 17865141 TI - CONGENITAL TUMORS OF THE COCCYGEAL REGION. PMID- 17865142 TI - MELANOMA OF THE NAIL BED. PMID- 17865143 TI - FRACTURES OF THE SHAFT OF THE FEMUR: TREATMENT BY MEANS OF BALANCED TRACTION ANALYSIS OF IMMEDIATE RESULTS IN FORTY CASES. PMID- 17865144 TI - ASTRAGALECTOMY (THE WHITMAN OPERATION) IN PARALYTIC DEFORMITIES OF THE FOOT. PMID- 17865145 TI - RADIUM IN THE TREATMENT OF PROSTATIC CARCINOMA. PMID- 17865146 TI - THE INDICATIONS FOR OPERATION IN THE TREATMENT OF TUBERCULOUS CERVICAL LYMPH GLANDS: A PRELIMINARY REPORT. PMID- 17865148 TI - AN EXTRAPERITONEAL INTRAPLEURAL ROUTE OF APPROACH FOR INTRATHORACIC SURGERY. PMID- 17865147 TI - RUPTURE OF THE DIAPHRAGM. PMID- 17865149 TI - ACUTE APPENDICITIS IN THE INFANT: FACTORS ACCOUNTABLE FOR ITS HIGH MORTALITY. PMID- 17865151 TI - LATE RECURRENCE AFTER RADICAL OPERATION FOR CARCINOMA OF THE BREAST. PMID- 17865150 TI - THE CLINICAL SIGNIFICANCE OF THE RELATION OF TOTAL AND DIFFERENTIAL LEUCOCYTE COUNTS IN ACUTE APPENDICITIS. PMID- 17865152 TI - IMPROVED TECHNIC FOR INTESTINAL ANASTOMOSIS. PMID- 17865154 TI - LARGE, MALIGNANT, FACIAL TUMOR REMOVED WITHOUT HEMORRHAGE BY BIPOLAR ENDOTHERMY AND THE ENDOTHERM KNIFE. PMID- 17865153 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held October 8, 1924. PMID- 17865155 TI - INTRAVENOUS ADMINISTRATION OF UROTROPIN FOR POST-OPERATIVE URINE RETENTION. PMID- 17865157 TI - THE EARLY DAYS OF THE ANNALS OF SURGERY. PMID- 17865156 TI - PRIMARY PNEUMOCOCCAL PERITONITIS. PMID- 17865158 TI - ANEURISM OF THE RENAL ARTERY. PMID- 17865159 TI - LATENT JAUNDICE AS A SYMPTOM OF BILIARY COLIC. PMID- 17865160 TI - SOME FRACTURE CALAMITIES AND THEIR MANAGEMENT. PMID- 17865162 TI - ACUTE PANCREATITIS. PMID- 17865161 TI - ON THE RESECTION OF THE STOMACH BY KOCHER'S METHOD. PMID- 17865163 TI - THE TREATMENT OF CHRONIC RECURRENT DISLOCATION OF THE SHOULDER BY CRUCIAL CAPSULAR PLICATION. PMID- 17865164 TI - SURGERY OF JUXTA-PYLORIC ULCER: REPORT OF OPERATIVE RESULTS OBTAINED AT THE U. S. NAVAL HOSPITAL OF BROOKLYN, N. Y. PMID- 17865165 TI - AMPUTATIONS IN INDUSTRIAL SURGERY. PMID- 17865166 TI - THORACIC SURGERY AS A SPECIALTY. PMID- 17865167 TI - GAS GANGRENE: WITH SPECIAL REFERENCE TO ITS TREATMENT. PMID- 17865168 TI - CRANIOTOMY UNDER LOCAL ANAESTHESIA. PMID- 17865169 TI - THE DIAGNOSIS AND LOCALIZATION OF SPINAL CORD TUMORS. PMID- 17865170 TI - SPASMODIC TORTICOLLIS. PMID- 17865171 TI - PRACTICAL POINTS IN CONNECTION WITH GOITRE SURGERY. PMID- 17865172 TI - THE EXPERIMENTAL TRANSPLANTATION OF THE DIAPHRAGM AS AN ADJUNCT IN THE TREATMENT OF LESIONS AT THE LOWER END OF THE OESOPHAGUS: APPLICATION OF THE METHOD IN A CASE OF CARCINOMA OF THE CARDIAC END OF THE OESOPHAGUS IN MAN. PMID- 17865173 TI - THE SURGERY OF JAUNDICE. PMID- 17865174 TI - JAUNDICE: ITS PATHOLOGICAL PHYSIOLOGY. PMID- 17865175 TI - MASTERS OF SURGERY IN THE EARLY YEARS OF THE ANNALS OF SURGERY. PMID- 17865176 TI - INTERNAL BILIARY FISTULA. PMID- 17865177 TI - HOUR-GLASS STOMACH AND DUODENUM. PMID- 17865178 TI - DIVERTICULITIS OF THE COLON: CLINICAL TYPES AND TREATMENT. PMID- 17865179 TI - POST-OPERATIVE COMPLICATIONS OF ABDOMINAL OPERATIONS. PMID- 17865181 TI - SOME UNUSUAL NEW GROWTHS IN THE REGION OF THE INGUINAL AND THE FEMORAL CANALS. PMID- 17865180 TI - THE RATIONAL TREATMENT OF SLIDING HERNIA. PMID- 17865182 TI - PELVIC ACTINOMYCOSIS: A STUDY OF FIVE CONSECUTIVE CASES SUCCESSFULLY TREATED BY OPERATION. PMID- 17865183 TI - THEORY AND TREATMENT OF SPIRAL FRACTURES. PMID- 17865184 TI - THE ABDUCTION TREATMENT OF FRACTURE OF THE NECK OF THE FEMUR: AN ACCOUNT OF THE EVOLUTION OF A METHOD ADEQUATE TO APPLY SURGICAL PRINCIPLES AND THEREFORE THE EXPONENT OF RADICAL REFORM OF CONVENTIONAL TEACHING AND PRACTICE. PMID- 17865185 TI - SPINAL ANAESTHESIA. PMID- 17865187 TI - FELLOW WORKERS' APPRECIATION OF TWO SCORES OF YEARS OF EDITORIAL WORK. PMID- 17865186 TI - THE STORY OF THE ANNALS. PMID- 17865188 TI - PYLORUS SPASM AND ITS SURGICAL TREATMENT. PMID- 17865189 TI - ANTETHORACIC OESOPHAGOPLASTY: A NEW METHOD. PMID- 17865190 TI - SO-CALLED IDIOPATHIC DILATATION OF THE OESOPHAGUS: SYNONYMS: DILATATIO FUSIFORMIS OESOPHAGI, CARDIOSPASMUS, MEGAOESOPHAGUS FIVE CASES, OF WHICH FOUR HAVE BEEN TREATED BY MEANS OF OESOPHAGO-GASTROSTOMIA SUBDIAPHRAGMATICA. PMID- 17865191 TI - LUPUS IN ITS SURGICAL ASPECTS. PMID- 17865192 TI - CLINICAL NOTES ON TUBERCULOSIS OF THE KIDNEY: A. RENAL TUBERCULOSIS AND TRAUMA B. TUBERCULOUS KIDNEY WITH DUPLICATION OF RENAL PELVIS AND URETER. PMID- 17865193 TI - NEURO-EPITHELIOMA OF THE SPINAL CORD: A CLINICAL AND PATHOLOGICAL STUDY. PMID- 17865194 TI - PRIMARY SARCOMA OF THE SPINE. PMID- 17865196 TI - LIGATION OF THE ABDOMINAL AORTA: REPORT OF THE ULTIMATE RESULT, ONE YEAR, FIVE MONTHS AND NINE DAYS AFTER LIGATION OF THE ABDOMINAL AORTA FOR ANEURISM AT THE BIFURCATION. PMID- 17865195 TI - THE EARLY TREATMENT OF SUPERFICIAL BURNS. PMID- 17865198 TI - SO-CALLED IDIOPATHIC DILATATION OF THE OESOPHAGUS: TREATMENT AND REPORT OF CASES. PMID- 17865197 TI - CONGENITAL ARTERIOVENOUS FISTULA OF LEFT BRACHIAL ARTERY AND VEIN WITH SECONDARY ARTERIAL BLOOD SUPPLY TO THE ARM. PMID- 17865199 TI - A SUGGESTION FOR THE RELIEF FOR THE PAIN FROM CARCINOMA OF THE MOUTH AND CHEEK. PMID- 17865200 TI - KIDNEY GUMMATA. PMID- 17865201 TI - PERIRENAL HYDRONEPHROSIS: WITH COMMENTS ON THE TECHNIC OF ABDOMINAL EXTRAPERITONEAL NEPHRECTOMY. PMID- 17865202 TI - SITUS INVERSUS ABDOMINALIS COMPLICATED BY ILEO-CAECAL TUBERCULOSIS PRODUCING ACUTE INTESTINAL OBSTRUCTION. PMID- 17865203 TI - THE RELATION OF THE APPENDIX TO THE RIGHT KIDNEY AND URETER. PMID- 17865204 TI - INTRA-APPENDICAL POLYP. PMID- 17865205 TI - HERNIA FOLLOWING THE USE OF THE McBURNEY INCISION IN OPERATIONS FOR APPENDICITIS. PMID- 17865206 TI - REMOVAL OF SCREWS AND PLATES AFTER INSERTION IN BONE. PMID- 17865207 TI - STATISTICAL RESULTS OF THE RADIOGRAPHIC STUDY OF INJURIES ABOUT THE WRIST-JOINT. PMID- 17865208 TI - FRONTAL FRACTURES OF THE PATELLA. PMID- 17865209 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held October 6, 1924. PMID- 17865210 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held November 3, 1924. PMID- 17865211 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held October 22, 1924. PMID- 17865212 TI - ADHESIONS OF THE ILEUM-THE RESULT OF APPENDICITIS. PMID- 17865213 TI - OVARIAN CYST OF GREAT SIZE REMOVAL WITH RECOVERY. PMID- 17865214 TI - AN IMPROVED OPERATING TABLE, FOR GENERAL SURGERY, PROVIDING NEW FEATURES FOR UROLOGIC AND GYNAECOLOGIC WORK. PMID- 17865215 TI - THE SURGICAL TREATMENT OF CLEFT PALATE. PMID- 17865216 TI - CERVICAL SYMPATHECTOMY FOR ANGINA PECTORIS. PMID- 17865217 TI - THE SURGICAL TREATMENT OF ANGINA PECTORIS. PMID- 17865218 TI - SWELLINGS OF THE SUBMAXILLARY REGION. PMID- 17865220 TI - GASTRIC TETANY. PMID- 17865219 TI - THE RELATION OF THE SUBMAXILLARY SALIVARY GLAND TO INFECTIONS OF THE SUBMAXILLARY TRIANGLE OF THE NECK. PMID- 17865221 TI - THE OPERATIVE TREATMENT OF DUODENAL ULCER WITH SPECIAL REFERENCE TO THE HORSLEY OPERATION. PMID- 17865222 TI - ACUTE INTUSSUSCEPTION IN CHILDREN: OBSERVATIONS ON THIRTY-ONE CASES ADMITTED TO THE CHILDREN'S HOSPITAL IN PHILADELPHIA. PMID- 17865223 TI - ASEPTIC END-TO-END INTESTINAL ANASTOMOSIS. PMID- 17865224 TI - ASEPTIC END-TO-END ANASTOMOSIS OF THE INTESTINE. PMID- 17865225 TI - SARCOMA ASSOCIATED WITH OVARIAN FIBROMA. PMID- 17865226 TI - SOME UNUSUAL CASES OF MALIGNANT NEOPLASMS. PMID- 17865227 TI - RESULTS OF THE INTRAVENOUS USE OF GENTIAN VIOLET IN CASES OF EXTREME SEPTICAEMIA. PMID- 17865228 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held November 12, 1924. PMID- 17865229 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held November 26, 1924. PMID- 17865231 TI - ANURIA FOLLOWING TRANSFUSION: EFFECT OF DECAPSULATION OF BOTH KIDNEYS. PMID- 17865230 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held December 1, 1924. PMID- 17865232 TI - THE EFFECT OF THE ADMINISTRATION OF IODINE UPON EXOPHTHALMIC GOITRE: A STUDY OF SEVENTY CASES THUS TREATED. PMID- 17865233 TI - NEW THORACOPLASTIC PROCEDURE FOR PULMONARY TUBERCULOSIS TO LESSEN INCIDENCE OF POST-OPERATIVE PNEUMONIA. PMID- 17865234 TI - SUTURE OF STAB WOUND OF THE HEART: TWO CASES WITH ONE RECOVERY. PMID- 17865236 TI - SYPHILIS OF THE STOMACH: A CRITICAL REVIEW OF REPORTED CASES FROM THE PATHOLOGICAL AND CLINICAL VIEWPOINTS. PMID- 17865235 TI - CHOLECYSTECTOMY; EXTERNAL AND INTERNAL CHOLECYSTOSTOMY. PMID- 17865237 TI - DUODENO-JEJUNOSTOMY. PMID- 17865239 TI - TUBERCULOMA OF THE CAECUM: HYPERPLASTIC TUBERCULOSIS. PMID- 17865238 TI - ENTERO-MESENTERIC CYSTS. PMID- 17865240 TI - OVARIAN DERMOIDS: A STUDY OF ONE HUNDRED CONSECUTIVE CASES. PMID- 17865241 TI - THE SUTURE OF THE APONEUROSIS OF THE INTERNAL OBLIQUE MUSCLE TO THE LIGAMENT OF POUPART. PMID- 17865243 TI - XANTHOSARCOMA OF THUMB: A CENTRAL BENIGN GIANT-CELL TUMOR OF THE PROXIMAL PHALANX OF THE THUMB. PMID- 17865242 TI - STRICTURE OF THE URETER. PMID- 17865244 TI - KIENBOCH'S DISEASE OF THE SEMILUNAR BONE. PMID- 17865245 TI - MICROSCOPIC EXAMINATION OF FRESH TISSUE. PMID- 17865246 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 10, 1924: Stated Meeting Held December. PMID- 17865248 TI - Actinomycosis of the Tongue. PMID- 17865247 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 5, 1925: Stated Meeting Held January. PMID- 17865250 TI - Lipoma of the Inguinal Canal. PMID- 17865249 TI - Complete Posterior Dislocation of Ankle. PMID- 17865251 TI - Anomaly of Testis. PMID- 17865253 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held January 14, 1925. PMID- 17865252 TI - POLYPOSIS OF THE APPENDIX VERMIFORMIS WITH INTUSSUSCEPTION OF THE APPENDIX. PMID- 17865254 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held January 28, 1925. PMID- 17865255 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held February 2, 1925. PMID- 17865256 TI - PATENT URACHUS. PMID- 17865257 TI - CHRONIC POST-CAECAL SUPPURATIVE APPENDICITIS CAUSING LUMBAR ABSCESS. PMID- 17865258 TI - SOME SURGICAL ASPECTS OF THE PATHOLOGY OF GLIOMAS OF THE BRAIN. PMID- 17865260 TI - SPLENIC BLOOD DISORDERS: A SURGICAL CLASSIFICATION WITH REFERENCE TO SPLENECTOMY. PMID- 17865259 TI - MANAGEMENT OF INTRACRANIAL INJURIES WITH OR WITHOUT FRACTURE. PMID- 17865261 TI - DRAINAGE OF THE THORACIC DUCT IN EXPERIMENTAL PERITONITIS. PMID- 17865262 TI - SURGICAL EMERGENCIES OF THE ABDOMEN. PMID- 17865263 TI - ON THE VIABILITY OF THE INTESTINE IN INTESTINAL OBSTRUCTION. PMID- 17865264 TI - THE ROLE OF THE PYLORO-DUODENAL NERVE SUPPLY IN THE SURGERY OF DUODENAL ULCER. PMID- 17865265 TI - BENIGN TUMORS OF THE STOMACH. PMID- 17865266 TI - GALL-STONES AND DISEASES OF THE GALL-BLADDER. PMID- 17865268 TI - CANCER OF RECTUM AND RECTO-SIGMOID. PMID- 17865267 TI - SURGERY OF THE GALL-BLADDER AND DUCTS. PMID- 17865269 TI - A CONTRIBUTION TO THE STUDY OF THROMBO-ANGIITIS OBLITERANS. PMID- 17865271 TI - A METHOD FOR EXPOSING THE ANTERIOR PORTION OF THE FRONTAL LOBES OF THE BRAIN. PMID- 17865270 TI - THE ELIMINATION OF MORPHIN AND OTHER ACCESSORY DRUGS IN OPERATIONS UNDER LOCAL ANAESTHESIA. PMID- 17865272 TI - SOME ASPECTS OF THE DIAGNOSIS AND SURGICAL TREATMENT OF TUMORS OF THE SPINAL CORD: WITH A STUDY OF THE END RESULTS IN A SERIES OF 119 OPERATIONS. PMID- 17865273 TI - BONE TUMORS: ANALYSIS OF ONE THOUSAND CASES WITH SPECIAL REFERENCE TO LOCATION, AGE AND SEX. PMID- 17865274 TI - PLEXIFORM NEUROMA. PMID- 17865275 TI - FINAL RESULTS OF THE OPERATIVE TREATMENT OF GASTRIC ULCER: A STUDY OF TWENTY-TWO CASES SUBJECTED TO THE POLYA OPERATION OF PYLORIC RESECTION WITH GASTRO ENTEROSTOMY. PMID- 17865277 TI - PROSTATIC ABSCESS. PMID- 17865276 TI - THE OPERATIVE TREATMENT OF ARTHRITIS DEFORMANS OF THE HIP-JOINT. PMID- 17865278 TI - SPASTIC OBSTRUCTION TO THE URETERS. PMID- 17865280 TI - TRAUMATIC ANEURISM TREATED BY EXCISION AND END-TO-END ARTERIAL SUTURE. PMID- 17865279 TI - TORSION OF THE SPERMATIC CORD: REPORT OF TWO CASES WITH REVIEW OF LITERATURE. PMID- 17865281 TI - POST-OPERATIVE COMPLICATIONS: BASED UPON CASES AT THE LANKENAU HOSPITAL. PMID- 17865283 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held February 11, 1925. PMID- 17865282 TI - THE SURGICAL SERVICE AT THE HOSPITAL OF THE UNIVERSITY OF PENNSYLVANIA. PMID- 17865284 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held March 2, 1925. PMID- 17865285 TI - TRANSPLANTATION OF EXTROVERTED BLADDER INTO THE RECTUM. PMID- 17865286 TI - MECHANISM OF THE FORMATION AND GROWTH OF MALIGNANT TUMORS. PMID- 17865287 TI - PAPILLOMATA OF THE LARGE BOWEL. PMID- 17865288 TI - CARCINOMA OF THE BODY OF THE UTERUS: A STUDY OF FIFTY CASES AT THE MASSACHUSETTS GENERAL HOSPITAL. PMID- 17865289 TI - THE TRANSPLANTATION OF DISTANT SKIN FLAPS FOR THE CURE OF INTRACTABLE BASAL-CELL CARCINOMA. PMID- 17865291 TI - PRIMARY CARCINOMA OF THE DUODENUM: REPORT OF FIFTEEN VERIFIED CASES. PMID- 17865290 TI - METASTATIC CARCINOMA IN THE URETER: ASSOCIATED WITH URETERAL STRICTURE. PMID- 17865292 TI - EPITHELIOMAS IN SEBACEOUS CYSTS. PMID- 17865294 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SURGICAL 25, 1925: Joint Meeting with the Philadelphia Academy of Surgery, Held February. PMID- 17865293 TI - OPERATIVE TREATMENT OF CARCINOMA OF THE RECTUM: REPORT OF OPERATIONS AND PRESENTATION OF CASES. PMID- 17865295 TI - MALIGNANT TUMORS OF THE THYROID: EPITHELIAL TYPES. PMID- 17865296 TI - TUMORS OF THE MALE BREAST. PMID- 17865297 TI - BILATERAL MAMMARY CANCER OPERATIONS: ULTIMATE RESULTS IN NINETY-EIGHT CASES. PMID- 17865298 TI - PSEUDO RECURRENCES AFTER RADICAL AMPUTATION OF THE BREAST FOR CARCINOMA. PMID- 17865299 TI - ETIOLOGY OF CANCER OF THE STOMACH: A REVIEW OF ONE HUNDRED SIXTEEN CONSECUTIVE CASES OF CANCER OF THE STOMACH WITH PARTICULAR RELATION TO ETIOLOGY. PMID- 17865300 TI - CLINICAL CONSIDERATIONS OF THROMBOSIS AND EMBOLISM. PMID- 17865301 TI - INTRACRANIAL TUMORS AND ABSCESSES CAUSING COMMUNICATING HYDROCEPHALUS. PMID- 17865302 TI - LENGTHENING THE SOFT PALATE IN CLEFT PALATE OPERATIONS. PMID- 17865303 TI - EPIGASTRIC PAIN A SYMPTOM OF OESOPHAGEAL OBSTRUCTION. PMID- 17865305 TI - HERNIA OF THE LUNG. PMID- 17865304 TI - IMPROVED GOITRE TECHNIC. PMID- 17865306 TI - SOME CONSIDERATIONS PERTAINING TO THE DIAGNOSIS AND SURGICAL TREATMENT OF DISEASES OF THE GALL-BLADDER. PMID- 17865307 TI - WANDERING SPLEEN WITH TORSION OF ITS PEDICLE. PMID- 17865308 TI - SPONTANEOUS RUPTURE OF THE SPLEEN. PMID- 17865309 TI - DIVERTICULA OF THE JEJUNUM. PMID- 17865310 TI - APPENDICITIS AND TRANSPOSITION OF THE VISCERA. PMID- 17865311 TI - THE "LIGATION AND DROP" TREATMENT OF THE APPENDECTOMY STUMP: RESULTS OF 3500 CASES. PMID- 17865312 TI - HERNIA OF THE BLADDER: A BRIEF REVIEW OF THE LITERATURE WITH A CASE REPORT AND A SUGGESTION OF A POSITIVE METHOD FOR PRE-OPERATIVE DIAGNOSIS. PMID- 17865313 TI - GRANULOMA INGUINALE. PMID- 17865314 TI - CYSTS OF THE ILIO-PSOAS BURSA. PMID- 17865315 TI - VERTEBRAL EPIPHYSITIS. PMID- 17865316 TI - CLOSED REDUCTION OF ACUTE DISLOCATIONS OF THE SEMILUNAR CARPAL BONE. PMID- 17865318 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held April 6, 1925. PMID- 17865317 TI - ARTERIOVENOUS FISTULA. PMID- 17865319 TI - CURE OF INTESTINAL FISTULA NEAR THE DUODENO-JEJUNAL JUNCTION. PMID- 17865320 TI - TORSION OF THE GREAT OMENTUM. PMID- 17865321 TI - NOTE ON THE TREATMENT OF ABDOMINAL SEPSIS. PMID- 17865322 TI - THE SURGICAL TREATMENT OF HABITUAL CRIMINALS, IMBECILES, PERVERTS, PAUPERS, MORONS, EPILEPTICS, AND DEGENERATES. PMID- 17865323 TI - THE CONCEPTION OF SEPTICAEMIA AND THE FATE OF MICROBES IN THE BLOOD STREAM. PMID- 17865324 TI - FAT EMBOLISM: WITH STUDY OF TWO FATAL CASES. PMID- 17865325 TI - OPERATIVE TREATMENT OF ANGINA PECTORIS. PMID- 17865326 TI - ACUTE MASSIVE COLLAPSE OF THE LUNGS: A DISCUSSION OF ITS MECHANISM AND OF ITS RELATION TO FOREIGN BODIES IN THE BRONCHI AND POST-OPERATIVE COMPLICATIONS. PMID- 17865327 TI - EXTRACTION THROUGH THE THORAX OF PROJECTILES LONG RESIDENT IN THE LUNG. PMID- 17865328 TI - AN EVALUATION OF PRE-OPERATIVE AND POST-OPERATIVE RADIATION IN THE TREATMENT OF MAMMARY CARCINOMA: A PRELIMINARY REPORT. PMID- 17865329 TI - SPLENECTOMY FOR PURPURA HEMORRHAGICA. PMID- 17865330 TI - THE SEQUELAE OF GASTRO-ENTEROSTOMY: THE INDICATIONS FOR DISCONNECTING THE ANASTOMOSIS, AND THE TECHNIC OF THE OPERATION. PMID- 17865331 TI - PRIMARY CARCINOMA OF THE SMALL INTESTINE IN AN OCTOGENARIAN. PMID- 17865332 TI - INTUSSUSCEPTION IN ADULTS DUE TO THE INVAGINATION OF A MECKEL'S DIVERTICULUM. PMID- 17865333 TI - ANATOMY AND TREATMENT OF REDUCIBLE OBLIQUE INGUINAL HERNIA. PMID- 17865334 TI - BROKEN-DOWN ABDOMINAL INCISIONS: A METHOD OF CLOSURE. PMID- 17865336 TI - METHODS OF URETERAL REPAIR AND TRANSPLANTATION. PMID- 17865335 TI - PARTIAL RESECTION OF THE KIDNEY. PMID- 17865337 TI - IMPLANTATION OF AN OVARY. PMID- 17865338 TI - MANAGEMENT OF BILATERAL OVARIAN DERMOIDS. PMID- 17865339 TI - TREATMENT OF UTERINE FIBROIDS. PMID- 17865341 TI - A HANGER METHOD FOR THE REPAIR OF PROCIDENTIA UTERI. PMID- 17865340 TI - TREATMENT OF UTERINE PROLAPSE AND RECTOCELE BY CLOSURE OF THE POUCH OF DOUGLAS: JONES-MOSCHCOWITZ. PMID- 17865342 TI - LATE RESULT OF NEEDLING AN AORTIC ANEURISM. PMID- 17865343 TI - CONTRIBUTIONS TO BRAIN SURGERY: A. REMOVAL OF CERTAIN DEEP-SEATED BRAIN TUMORS B. INTRACRANIAL APPROACH WITH CONCEALED INCISIONS. PMID- 17865344 TI - RENAL TUBERCULOSIS: A CLINICAL SURVEY OF 295 CASES, 90 OF WHICH WERE NOT OPERATED ON. PMID- 17865345 TI - MALIGNANT TUMORS OF THE TESTICLE: A PATHOLOGICAL STUDY. PMID- 17865346 TI - RETROPERITONEAL HERNIA. PMID- 17865347 TI - OBSERVATIONS ON THE HISTOLOGIC AND PATHOLOGIC ANATOMY OF THE HEPATIC, CYSTIC, AND COMMON BILE DUCTS. PMID- 17865348 TI - SPONTANEOUS RUPTURE OF THE SPLEEN. PMID- 17865349 TI - FASCIAL BANDS AS SUPPORTS TO RELAXED FACIAL TISSUE. PMID- 17865350 TI - COMPENSATORY LENGTHENING OF THE FEMUR IN CHILDREN AFTER FRACTURE. PMID- 17865352 TI - TRAUMATIC LUXATION OF THE HEAD OF THE FIBULA. PMID- 17865351 TI - ACTIVE MOTION IN THE TREATMENT OF FRACTURES. PMID- 17865353 TI - THE EFFICIENCY AND INEFFICIENCY OF CERTAIN SKIN ANTISEPTICS. PMID- 17865354 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held March 11, 1925. PMID- 17865355 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held March 25, 1925. PMID- 17865357 TI - ACUTE HYPOTENSION OF CEREBRO-SPINAL FLUID FOLLOWING CRANIAL TRAUMATISM. PMID- 17865356 TI - EPITHELIAL HYPERPLASIA OF THE BREAST. PMID- 17865358 TI - END RESULTS IN NEURO-SURGERY: IMPRESSIONS DURING DECADE 1913-1923. PMID- 17865359 TI - SURGICAL TREATMENT OF EPILEPSIA PARTIALIS CONTINUA (KOJEVNICKOVI). PMID- 17865360 TI - PERIARTERIAL SYMPATHECTOMY. PMID- 17865361 TI - NEOPLASMS OF THE BLOOD-LYMPH-VASCULAR SYSTEM WITH SPECIAL REFERENCE TO ENDOTHELIOMAS. PMID- 17865362 TI - THE KLIPPEL-FEIL SYNDROME: NUMERICAL REDUCTION OF CERVICAL VERTEBRAE. PMID- 17865363 TI - HORSESHOE KIDNEY. PMID- 17865364 TI - NON-PARASITIC CHYLURIA. PMID- 17865365 TI - THE MECHANISM OF ACUTE OSTEOMYELITIS. PMID- 17865366 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held April 8, 1925. PMID- 17865367 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held April 22, 1925. PMID- 17865368 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held May 8, 1925. PMID- 17865369 TI - CANCER OF THE THYROID AND ITS PRESENT-DAY TREATMENT: EMBODYING THE EXPERIENCE OF THE MEMORIAL HOSPITAL OF NEW YORK. PMID- 17865371 TI - COMPRESSION OF THE SPINAL CORD BY TUMOR. PMID- 17865370 TI - CONGENITAL CYSTS AND FISTULAE OF THE NECK: A REVIEW OF 42 THYROGLOSSAL CYSTS AND FISTULAE. PMID- 17865372 TI - ORIGIN AND DEVELOPMENT OF THE BLOOD SUPPLY OF WHOLE-THICKNESS SKIN GRAFTS: AN EXPERIMENTAL STUDY. PMID- 17865373 TI - X-RAY AS A DIAGNOSTIC AID IN CASES OF HAEMANGIOMA. PMID- 17865374 TI - MYOSITIS OSSIFICANS CIRCUMSCRIPTA: A CLINICAL AND EXPERIMENTAL STUDY. PMID- 17865375 TI - GASTRIC RESECTION FOR PYLORIC AND DUODENAL ULCER: A PRELIMINARY REPORT. PMID- 17865376 TI - FAILURE OF GASTRO-ENTEROSTOMY TO EFFECT A DECISIVE REDUCTION IN GASTRIC ACIDITY. PMID- 17865378 TI - NOTE ON BENIGN TUMORS OF THE DUODENUM. PMID- 17865377 TI - INFANTILE PYLORIC STENOSIS. PMID- 17865379 TI - PANCREATIC LITHIASIS. PMID- 17865380 TI - THE RELATION OF TOTAL AND POLYMORPHONUCLEAR LEUCOCYTE COUNTS IN CHRONIC APPENDICITIS. PMID- 17865381 TI - TECHNIQUE FOR THE REMOVAL OF HEMORRHOIDS. PMID- 17865383 TI - PREHERNIAL LIPOMA. PMID- 17865382 TI - BILATERAL DUPLICATION OF RENAL PELVES AND URETERS. PMID- 17865384 TI - THE VALUE OF BLOOD TRANSFUSION IN SURGERY OF THE PROSTATE. PMID- 17865385 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held May 13, 1925. PMID- 17865386 TI - DIVERTICULA OF THE OESOPHAGUS, PULSION, TRACTION, MALIGNANT AND CONGENITAL. PMID- 17865387 TI - ARTHRODESIS OF THE ELBOW. PMID- 17865388 TI - REPAIR OF WOUNDS OF THE FLEXOR TENDONS OF THE HAND. PMID- 17865389 TI - A SKIN FLAP COVER FOR PROJECTING INTESTINE. PMID- 17865390 TI - A PERINEAL ELEVATOR. PMID- 17865391 TI - STITCH INTERPOLATION IN ARTERIAL AND VENOUS ANASTOMOSIS. PMID- 17865392 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held October 5, 1925. PMID- 17865393 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held October 14, 1925. PMID- 17865394 TI - THE ODONTOID OSSICLE OF THE SECOND CERVICAL VERTEBRA. PMID- 17865395 TI - THE DANGER IN THE USE OF LIPIODOL IN THE DIAGNOSIS OF OBSTRUCTIVE LESIONS OF THE SPINAL CANAL. PMID- 17865396 TI - THE RADICAL BREAST OPERATION WITH THE ENDOTHERM KNIFE (ACUSECTOR) AND WITHOUT LIGATURES. PMID- 17865397 TI - OBSERVATIONS ON THE TREATMENT OF GALL-STONES. PMID- 17865398 TI - RUPTURE OF AN INTRAHEPATIC BILE DUCT WITH FATAL PERITONITIS. PMID- 17865399 TI - THE MECHANISM OF INTESTINAL PERFORATION DUE TO DISTENTION. PMID- 17865400 TI - THE ILIO-HYPOGASTRIC NERVE IN RELATION TO HERNIOTOMY. PMID- 17865401 TI - MULTIPLE SACS IN INGUINAL HERNIA. PMID- 17865402 TI - DISLOCATION OF THE SHOULDER. PMID- 17865403 TI - CANCER OF THE HEART: SECONDARY TO CANCER OF THE BREAST BY DIRECT LYMPHATIC EXTENSION. PMID- 17865404 TI - THE DEVELOPMENT OF CARCINOMA IN SCAR TISSUE FOLLOWING BURNS. PMID- 17865405 TI - TUBERCULOSIS OF THE BREAST: AS OBSERVED AT BELLEVUE HOSPITAL OF NEW YORK CITY. PMID- 17865406 TI - TUBERCULOSIS OF THE MAMMARY GLAND. PMID- 17865408 TI - PARTIAL NEURECTOMY OF THE SENSORY ROOT OF THE GASSERIAN GANGLION IN TRIFACIAL NEURALGIA WITH PRESERVATION OF CORNEAL SENSATION. PMID- 17865407 TI - DIAGNOSIS AND TREATMENT OF FRACTURES OF THE SKULL AS DEVELOPED IN THE CINCINNATI GENERAL HOSPITAL. PMID- 17865409 TI - PERSISTENT AND RECURRENT HYPERTHYROIDISM. PMID- 17865410 TI - OSTEOMYELITIS OF THE STERNUM. PMID- 17865411 TI - THE SURGERY OF GASTRIC AND DUODENAL ULCERS: EXPERIENCES OF THE FIRST SURGICAL CLINIC UNIVERSITY OF BUDAPEST (DIRECTOR PROF. T. DE VEREBELY). PMID- 17865412 TI - A STUDY OF 6797 SURGICALLY REMOVED APPENDICES. PMID- 17865413 TI - PYELOGRAPHY IN RENAL DIAGNOSIS. PMID- 17865414 TI - THE ETIOLOGY OF THE POST-OPERATIVE PULMONARY ABSCESS. PMID- 17865415 TI - THE TREATMENT OF TRAUMATIC RUPTURE OF THE KIDNEY. PMID- 17865416 TI - TREATMENT OF OBSTRUCTIONS OF THE UPPER URETER AND EARLY HYDRONEPHROSIS. PMID- 17865417 TI - FRACTURES OF THE HEAD AND NECK OF THE RADIUS. PMID- 17865419 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held October 28, 1925. PMID- 17865418 TI - LATE RESULTS IN TREATMENT OF SIMPLE FRACTURE OF THE FEMUR IN ADULTS. PMID- 17865421 TI - INTESTINAL OBSTRUCTION FROM DIRECT TRAUMA. PMID- 17865420 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held November 2, 1925. PMID- 17865422 TI - FIBROMA OF THE MESENTERY. PMID- 17865423 TI - INVASION OF THE INTRACRANIAL VENOUS SINUSES BY MENINGIOMA (DURAL ENDOTHELIOMA). PMID- 17865424 TI - GIANT-CELL TUMOR INVOLVING PHALANGES. PMID- 17865425 TI - PERI-ARTERIAL SYMPATHECTOMY: REPORT OF THREE CASES IN WHICH IT FAILED. PMID- 17865426 TI - GLOSSOPHARYNGEAL NEURALGIA AND ITS SURGICAL RELIEF. PMID- 17865427 TI - QUESTIONS INVOLVED IN OPERATIVE PROCEDURES IN CASES OF GASTRIC AND DUODENAL ULCERS. PMID- 17865428 TI - THE HEALING OF THE GASTRIC ULCER IN MAN. PMID- 17865429 TI - CARCINOMA OF THE RIGHT SEGMENT OF THE COLON. PMID- 17865430 TI - COLONIC POLYPOSIS WITH ENGRAFTED MALIGNANCY: A TECHNIC FOR REMOVING THE ENTIRE COLON INCLUDING THE RECTUM. PMID- 17865432 TI - ARTHROTOMY FOR KNEE-JOINT CALCULI. PMID- 17865431 TI - HAEMOSTASIS IN SUPRAPUBIC PROSTATECTOMY. PMID- 17865433 TI - PRIMARY PNEUMOCOCCUS PERITONITIS. PMID- 17865434 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held November 11, 1925. PMID- 17865435 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held November 25, 1925. PMID- 17865437 TI - ACTIVE MOTION IN THE TREATMENT OF FRACTURES. PMID- 17865436 TI - ISOLATED DISLOCATION OF THE FIRST METATARSAL BONE. PMID- 17865438 TI - THE EXCISION OF INTERNAL HEMORRHOIDS. PMID- 17865439 TI - AMOEBIC ABSCESS OF LIVER WITH RUPTURE INTO INFERIOR VENA CAVA. PMID- 17865440 TI - THE MANAGEMENT OF ADVANCED CANCER OF THE STOMACH. PMID- 17865441 TI - ABDOMINAL PUNCTURE IN THE DIAGNOSIS OF ACUTE INTRAPERITONEAL DISEASE. PMID- 17865442 TI - LOCAL VERSUS GENERAL ANAESTHESIA FOR UPPER ABDOMINAL OPERATIONS: A COMPARISON OF POST-OPERATIVE CONDITIONS. PMID- 17865443 TI - PENETRATING GASTRIC ULCER, SITUATED NEAR THE CARDIA. VISUALIZATION OF THE CARDIA. PMID- 17865445 TI - DILATATION OF THE COMMON BILE DUCT IN THE ABSENCE OF FUNCTIONING GALL-BLADDER. PMID- 17865444 TI - PEPTIC ULCER OF MECKEL'S DIVERTICULUM. PMID- 17865446 TI - ASEPTIC END-TO-END SUTURE OF INTESTINE. PMID- 17865448 TI - EXPERIMENTAL RESULTS IN THE USE OF DEAD FASCIA GRAFTS FOR HERNIA REPAIR. PMID- 17865447 TI - TUBERCULOSIS OF THE CAECUM. PMID- 17865449 TI - SKIN PLASTICS IN THE TREATMENT OF TRAUMATIC LESIONS OF THE HAND AND FOREARM. PMID- 17865450 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held December 9, 1925. PMID- 17865451 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held January 13, 1926. PMID- 17865452 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held January 4, 1926. PMID- 17865453 TI - DERMOID CYSTS OF THE MEDIASTINUM. PMID- 17865454 TI - HEMIGLOSSECTOMY BY ENDOTHERMY IN CARCINOMA OF THE TONGUE. PMID- 17865455 TI - TECHNIC OF USE OF REMOVABLE RADON SEEDS IN CARCINOMA OF THE TONGUE. PMID- 17865456 TI - THE EXPERIMENTAL PRODUCTION OF DUODENAL ULCER BY EXCLUSION OF BILE FROM THE INTESTINE. PMID- 17865457 TI - AIDS TO CHOLECYSTECTOMY. PMID- 17865458 TI - TUBERCULOSIS OF THE MESENTERIC LYMPH-GLANDS. PMID- 17865459 TI - PYELOGRAPHY IN THE DIAGNOSIS OF TUMORS OF THE FLANK. PMID- 17865460 TI - ACUTE KNEE-JOINT INJURIES. PMID- 17865461 TI - CUTANEOUS CARCINOMA OF THE LOWER EXTREMITIES: A STUDY OF CASES AT THE BARNES AND THE BARNARD FREE SKIN AND CANCER HOSPITALS OF ST. LOUIS, MO. PMID- 17865462 TI - SOME BIOLOGIC EVIDENCE OBTAINED FROM A STUDY OF CONGENITAL DISLOCATION OF HIPS IN IDENTICAL TWINS SUPPORTING THE DEVELOPMENTAL THEORY. PMID- 17865463 TI - ACUTE OSTEOMYELITIS IN CHILDREN. PMID- 17865464 TI - RECONSTRUCTION OF HIP-JOINT DISORGANIZED BY CHARCOT'S DISEASE. PMID- 17865465 TI - UNUNITED FRACTURE OF THE HIP. PMID- 17865466 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held January 27, 1926. PMID- 17865467 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held February 24, 1926. PMID- 17865468 TI - JOINT MEETING OF THE PHILADELPHIA ACADEMY OF SURGERY AND THE NEW YORK SURGICAL SOCIETY Held at the Jefferson Hospital, Philadelphia, February 10, 1926. PMID- 17865469 TI - TULAREMIA. PMID- 17865470 TI - TREATMENT OF ACUTE TRAUMATIC CRANIOCEREBRAL INJURIES. PMID- 17865472 TI - THE PREVENTION OF POST-OPERATIVE THYROTOXICOSIS BY POST-OPERATIVE IODINIZATION. PMID- 17865471 TI - ASYMMETRY OF THE MANDIBLE FROM UNILATERAL HYPERTROPHY. PMID- 17865473 TI - DISSECTION OF THE AXILLA IN RADICAL OPERATIONS FOR CANCER OF THE BREAST. PMID- 17865475 TI - EXTERNAL FECAL FISTULA FOLLOWING APPENDICITIS. PMID- 17865474 TI - A STUDY OF THE ACCESSORY PANCREAS: WITH REPORT OF ONE CAUSING CONGENITAL PYLORIC STENOSIS. PMID- 17865476 TI - THE PATHOGENIC COLON. PMID- 17865478 TI - RETROPERITONEAL TUBERCULOUS LYMPHADENITIS. PMID- 17865477 TI - PRIMARY TUBERCULOSIS OF THE GALL-BLADDER. PMID- 17865480 TI - PENETRATING BULLET-WOUND OF THORACIC AORTA FOLLOWED BY LODGEMENT OF THE BULLET IN THE FEMORAL ARTERY. PMID- 17865479 TI - MESENTERIC LYMPHADENITIS. PMID- 17865481 TI - A STUDY IN THE DISINFECTION OF THE HANDS. PMID- 17865482 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held March 10, 1926. PMID- 17865483 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held March 24, 1926. PMID- 17865484 TI - THE TREATMENT OF CUTANEOUS BURNS. PMID- 17865486 TI - THE SURGICAL TREATMENT OF ACUTE APPENDICITIS. PMID- 17865485 TI - ACUTE PRIMARY INTUSSUSCEPTION IN THE ADULT. PMID- 17865488 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 1, 1926: Stated Meeting Held March. PMID- 17865487 TI - DISLOCATION OF THE CARPAL SEMILUNAR BONE. PMID- 17865489 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 14, 1926: Stated Meeting Held April. PMID- 17865490 TI - Two Cases of Diaphragmatic Hernia. PMID- 17865491 TI - Acute Ileus from a Distended Bladder. PMID- 17865493 TI - STUDIES OF CALCIUM AND PHOSPHORUS METABOLISM IN THE FRACTURE OF BONES. PMID- 17865492 TI - BURNS TREATED BY TANNIC ACID. PMID- 17865494 TI - SPINAL ANAESTHESIA. PMID- 17865495 TI - A SYSTEM OF CONTROL AND TREATMENT IN THE TOXIC GOITRE. PMID- 17865496 TI - HYPERNEPHROMATA: AN EXPERIMENTAL AND CLINICAL RESEARCH. PMID- 17865497 TI - CHRONIC ULCER OF THE STOMACH: ITS EXPERIMENTAL PRODUCTION AND EFFECT ON GASTRIC SECRETION AND MOTILITY. PMID- 17865498 TI - CHOLECYST-DUODENOSTOMY. PMID- 17865499 TI - THE PSYCHOLOGY OF THE SICK MAN: PRESIDENTIAL ADDRESS, AMERICAN SURGICAL ASSOCIATION, MAY 24, 1926. PMID- 17865500 TI - THE "REHABILITATION" OF THE SURGICAL PATIENT THROUGH BIOCHEMICAL METHODS, WITH SPECIAL REFERENCE TO DIABETES. PMID- 17865501 TI - FINAL RESULTS IN THE SURGERY OF MALIGNANT DISEASE: STUDY OF A TWELVE YEAR FOLLOW UP. PMID- 17865502 TI - LATE RESULTS AFTER AMPUTATION OF THE BREAST FOR CARCINOMA. PMID- 17865504 TI - THE ART AND SCIENCE OF PLASTIC SURGERY. PMID- 17865503 TI - THE CAUSES OF CICATRICIAL CONTRACTION. PMID- 17865505 TI - CONGENITAL CLEFT LIP AND PALATE: A MUSCLE THEORY REPAIR OF THE LIP CLEFT. PMID- 17865506 TI - IMPORTANT FACTORS IN THE TREATMENT OF CLEFT LIP AND CLEFT PALATE. PMID- 17865507 TI - THE TREATMENT OF RODENT ULCERS BY RADIATION. PMID- 17865508 TI - FREE, FULL-THICKNESS SKIN GRAFTS. PMID- 17865509 TI - A PLASTIC OPERATION ON THE CHEST. PMID- 17865510 TI - THE ADVANTAGES OF THE PRIMARY SUPERIOR POLAR ATTACK IN THE REMOVAL OF SUBSTERNAL THYROIDS. PMID- 17865511 TI - THE EXPERIMENTAL PRODUCTION OF ABSCESS OF THE LUNG. PMID- 17865514 TI - A STUDY OF THE MORTALITY IN APPENDICITIS. PMID- 17865512 TI - THE OCCURRENCE AND MANAGEMENT OF GASTROJEJUNAL ULCER. PMID- 17865513 TI - SHORT MESOCOLON AS A COMPLICATION OF GASTRIC SURGERY. PMID- 17865515 TI - THE OPERATIVE TREATMENT OF THENAR PARALYSIS. PMID- 17865516 TI - CHOLESTEATOMATOUS CYSTS: WITH REPORT OF CASE INVOLVING THE MAXILLA. PMID- 17865518 TI - CONTROLLING BLEEDING FROM THE CYSTIC ARTERY. PMID- 17865517 TI - ANTERIOR GASTRO-JEJUNOSTOMY. PMID- 17865519 TI - THE VITALISTIC METHOD IN THE TREATMENT OF CERTAIN SURGICAL INFECTIONS. PMID- 17865520 TI - ON SIMPLE AND COMBINED LIGATIONS OF PULMONARY VESSELS: AN EXPERIMENTAL STUDY. PMID- 17865521 TI - LUNG ABSCESS. PMID- 17865522 TI - AN EXTRAPERITONEAL TRANSDIAPHRAGMATIC ROUTE FOR LOWER INTRATHORACIC SURGERY. PMID- 17865524 TI - SURGICAL ASPECTS OF CERTAIN PHASES OF LIVER FUNCTION. PMID- 17865523 TI - SOME NEW PHASES OF THE PHYSIOLOGY OF THE BILIARY TRACT. PMID- 17865525 TI - THE GALL-BLADDER OF 1926. PMID- 17865527 TI - DANGERS INCIDENT TO CHOLECYSTECTOMY: AN ANALYSIS OF 575 CASES OF CHOLECYSTECTOMY AND CHOLECYSTOSTOMY. PMID- 17865526 TI - PROBLEMS IN GALL-BLADDER SURGERY. PMID- 17865528 TI - THE SURGICAL MANAGEMENT OF THE COMPLICATIONS OF CHOLECYSTITIS. PMID- 17865529 TI - ASSOCIATION OF CHOLECYSTITIS WITH DUODENAL ULCER. PMID- 17865530 TI - STRICTURES AND OPERATIVE INJURIES OF THE BILE DUCTS. PMID- 17865531 TI - STRICTURE OF THE COMMON BILE DUCT. PMID- 17865532 TI - THE OPERATIVE MANAGEMENT OF COMMON DUCT STONES. PMID- 17865533 TI - HYDROPS OF THE GALL-BLADDER IN AN INFANT. PMID- 17865534 TI - MORTALITY FOLLOWING OPERATIONS ON THE BILIARY TRACT, PANCREAS AND LIVER. PMID- 17865536 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held April 5, 1926. PMID- 17865535 TI - PROGRESSIVE GANGRENOUS INFECTION OF THE SKIN AND SUBCUTANEOUS TISSUES, FOLLOWING OPERATION FOR ACUTE PERFORATIVE APPENDICITIS: A STUDY IN SYMBIOSIS. PMID- 17865537 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held May 3, 1926. PMID- 17865538 TI - THE HISTOLOGY OF SPINAL CORD AFTER SPINAL ANAESTHESIA. PMID- 17865539 TI - ALKALOSIS. PMID- 17865540 TI - ERRORS IN DIAGNOSIS OF SURGICAL CONDITIONS. PMID- 17865541 TI - THE SURGICAL ASPECT OF BLOOD DYSCRASIAS ASSOCIATED WITH SPLENOMEGALY. PMID- 17865542 TI - FIBROSARCOMATOUS TUMORS OF THE SKIN OF THE TRUNK: CHARACTERIZED BY ATTENUATED DERMAL SURFACES. PMID- 17865543 TI - EXOPHTHALMIC GOITRE AND TOXIC ADENOMA: SIMILARITY OF RESPONSE TO IODINE. PMID- 17865544 TI - THE FREQUENCY AND CHARACTER OF BLADDER DISTURBANCES IN NEWGROWTHS OF THE BRAIN AND SPINAL CORD. PMID- 17865545 TI - ANALOGIES BETWEEN THE BILIARY TRACT AND THE URINARY TRACT. PMID- 17865546 TI - AN ECTOPIC (PELVIC) COMPLETELY FUSED (CAKE) KIDNEY ASSOCIATED WITH VARIOUS ANOMALIES OF THE ABDOMINAL VISCERA. PMID- 17865547 TI - RENAL ARTERIAL VARIATIONS AND EXTRAPERITONEAL ABDOMINAL NEPHRECTOMY. PMID- 17865548 TI - URINARY OBSTRUCTIONS IN CHILDHOOD. PMID- 17865549 TI - ESSENTIAL THROMBOCYTOPENIC PURPURA-PURPURA HEMORRHAGICA AND ITS TREATMENT BY SPLENECTOMY. PMID- 17865550 TI - ACUTE PANCREATITIS. PMID- 17865551 TI - CYSTS OF THE OMENTUM. PMID- 17865552 TI - INTESTINAL OBSTRUCTION. PMID- 17865553 TI - INTESTINAL OBSTRUCTION FOLLOWING APPENDECTOMY: STUDY OF TWENTY-ONE CASES. PMID- 17865554 TI - THE REDUCTION OF COLONIC INTUSSUSCEPTION BY AIR INFLATION. PMID- 17865555 TI - MECHANICAL FACTORS IN CHRONIC APPENDICITIS. PMID- 17865556 TI - STABILIZATION OF PARALYTIC TALIPES VARUS. PMID- 17865557 TI - PARAFFINOMA OF THE KNEE. PMID- 17865558 TI - BRIEF COMMUNICATIONS. PMID- 17865559 TI - THE STERILIZATION OF INFECTED WOUNDS AND CHRONIC ULCERATIONS BY PERIARTERIAL SYMPATHECTOMY. PMID- 17865560 TI - CONCERNING INTRACRANIAL MALIGNANT METASTASES: THEIR FREQUENCY AND THE VALUE OF SURGERY IN THEIR TREATMENT. PMID- 17865561 TI - EXOPHTHALMOS: THE MECHANISM OF ITS PRODUCTION IN EXOPHTHALMIC GOITRE. PMID- 17865562 TI - THE PATHOGENESIS OF THE END RESULTS OF THE LESIONS OF ACUTE OSTEOMYELITIS. PMID- 17865564 TI - SYMMETRICAL LATERAL ABERRANT THYROIDS. PMID- 17865563 TI - NEW PRINCIPLES IN THE SURGICAL TREATMENT OF POSTERIOR CERVICAL CARBUNCLES. PMID- 17865565 TI - TUBERCULOSIS OF THE MAMMARY GLAND: A REVIEW OF THE LITERATURE AND REPORT OF SIX ADDITIONAL CASES. PMID- 17865566 TI - ON THE SIGNIFICANCE OF THE ESCAPE OF STERILE BILE INTO THE PERITONEAL CAVITY. PMID- 17865567 TI - LIVER FUNCTION STUDIES AND THEIR CLINICAL CORRELATIONS. PMID- 17865568 TI - THE TREATMENT OF PEPTIC ULCER FROM THE SURGICAL POINT OF VIEW. PMID- 17865569 TI - CONGENITAL CONSTRICTION OF THE DUODENUM DUE TO AN ABNORMAL FOLD OF THE ANTERIOR MESOGASTRIUM. PMID- 17865570 TI - PARALYTIC ILEUS AS A COMPLICATION OF ACUTE APPENDICITIS. PMID- 17865571 TI - CHRONIC INTUSSUSCEPTION IN CHILDREN: A CRITICISM OF THE TERM, WITH A REPORT OF NINE CASES OCCURRING IN CHILDREN. PMID- 17865572 TI - DIVERTICULOSIS OF THE DESCENDING COLON: A REVIEW OF SEVEN CASES. PMID- 17865573 TI - FORTIFYING THE TRIANGLE IN REPAIR OF INGUINAL HERNIA. PMID- 17865574 TI - GLUTEAL ANEURISM. PMID- 17865576 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held April 28, 1926. PMID- 17865575 TI - KIENBOCH'S DISEASE OF THE SEMILUNAR BONE. PMID- 17865577 TI - BRIEF COMMUNICATIONS. PMID- 17865578 TI - ISCHAEMIC CONTRACTURE: EXPERIMENTAL STUDY. PMID- 17865579 TI - MECHANICAL DERANGEMENTS OF THE JOINTS. PMID- 17865580 TI - TUBERCULOSIS OF THE THYROID GLAND: A REVIEW OF THE LITERATURE AND REPORT OF FIVE NEW CASES. PMID- 17865581 TI - SHOULD THE GALL-BLADDER BE REMOVED WITHOUT DRAINAGE? PMID- 17865582 TI - AN ANALYSIS OF FOUR HUNDRED AND EIGHTY-TWO GALL-BLADDER CASES: TREATED IN THE FIRST SURGICAL DIVISION OF THE NEW YORK HOSPITAL. PMID- 17865584 TI - EXTERNAL FECAL FISTULAE IN ACUTE APPENDICITIS. PMID- 17865583 TI - CANCER OF THE SIGMOID AND RECTUM IN CHILDREN AND YOUNG ADULTS. PMID- 17865585 TI - POST-OPERATIVE GAS BACILLUS INFECTION OF THE ABDOMINAL WALL. PMID- 17865587 TI - URETERAL CALCULI: BASED ON ONE HUNDRED CONSECUTIVE CASES. PMID- 17865586 TI - POLYCYSTIC KIDNEY. PMID- 17865588 TI - ABNORMAL DESCENT OF THE TESTICLE. PMID- 17865590 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held May 12, 1926. PMID- 17865589 TI - METASTATIC INTRAMUSCULAR GONOCOCCAL ABSCESS. PMID- 17865592 TI - SEPTIC OSTEOMYELITIS OF THE BONES OF THE SKULL AND FACE: A PLEA FOR CONSERVATIVE TREATMENT. PMID- 17865591 TI - BRIEF COMMUNICATIONS. PMID- 17865593 TI - THE DANGER OF INFECTION ABOUT THE FACE. PMID- 17865595 TI - THE VASOMOTOR REFLEX ARC. PMID- 17865594 TI - ADENOMA OF THE THYROID. PMID- 17865597 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 4, 1926: Stated Meeting Held October. PMID- 17865596 TI - MALIGNANT GROWTHS OF THE THYROID. PMID- 17865598 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 13, 1926: Stated Meeting Held October. PMID- 17865600 TI - BENIGN BONY ENLARGEMENT OF THE CONDYLOID PROCESS OF THE MANDIBLE. PMID- 17865599 TI - BRIEF COMMUNICATIONS. PMID- 17865601 TI - CEREBROSPINAL FLUID LEAK DUE TO A FISTULA OF THE CISTERNA MAGNA. PMID- 17865602 TI - OSTEOPLASTIC SUPPORT OF THE SPINE IN POTT'S DISEASE. PMID- 17865603 TI - OPERATIVE RELIEF OF LARYNGOSTENOSIS. PMID- 17865604 TI - POST-OPERATIVE PULMONARY EMBOLISM. PMID- 17865605 TI - POST-OPERATIVE MASSIVE COLLAPSE OF THE LUNG: REPORT OF BRONCHOSCOPIC OBSERVATIONS. PMID- 17865606 TI - MASSIVE HYPERTROPHY OF THE BREASTS. PMID- 17865607 TI - CONGENITAL HYPERTROPHIC PYLORIC STENOSIS: A STUDY BASED ON 48 PERSONAL CASES. PMID- 17865608 TI - DUODENAL DIVERTICULITIS: SECOND REPORT. PMID- 17865610 TI - THE MORTALITY IN APPENDICITIS. PMID- 17865609 TI - DIVERTICULITIS OF THE SIGMOID. PMID- 17865611 TI - THE REPAIR PROCESSES IN WOUNDS OF TENDONS, AND IN TENDON GRAFTS. PMID- 17865612 TI - A STUDY OF GAS GANGRENE IN CIVIL SURGERY. PMID- 17865614 TI - CONTRIBUTION TO PLASTIC SURGERY: REMOVAL OF SCARS BY STAGES; AN OPEN OPERATION FOR EXTENSIVE LACERATION OF THE ANAL SPHINCTER; THE KONDOLEON OPERATION FOR ELEPHANTIASIS. PMID- 17865613 TI - OBSERVATIONS ON THE SURGERY OF THE LARGE ARTERIES: WITH REPORT OF CASE OF LIGATION OF THE INNOMINATE ARTERY FOR VARICOSE ANEURISM OF THE SUBCLAVIAN VESSELS. PMID- 17865615 TI - ON THE USE OF LIPIODOL IN RELATION TO THORACIC SURGERY. PMID- 17865617 TI - THE SURGICAL PATHOLOGY OF THE GALL-BLADDER. PMID- 17865616 TI - OBSERVATIONS ON PEPTIC ULCER: I. A METHOD OF PRODUCING CHRONIC GASTRIC ULCER: A CONSIDERATION OF ETIOLOGY. PMID- 17865618 TI - GALL-BLADDER TECHNIC. PMID- 17865620 TI - CHILLS IN ACUTE APPENDICITIS: AN ANALYSIS OF 2841 CASES OF ACUTE APPENDICITIS TREATED IN MT. SINAI HOSPITAL OF NEW YORK CITY. PMID- 17865619 TI - ULCER OF MECKEL'S DIVERTICULUM AS A CAUSE OF INTESTINAL HEMORRHAGE. PMID- 17865621 TI - TRAUMATIC APPENDICITIS. PMID- 17865623 TI - LIPOMA OF THE TESTICLE: WITH A CONSIDERATION OF FAT ATTACHED TO THE INGUINAL AND SCROTAL PERITONEUM. PMID- 17865622 TI - GANGRENE OF THE BLADDER: REPORT OF ADDITIONAL CASES. PMID- 17865624 TI - TORSION OF AN INTRA-ABDOMINAL TESTIS. PMID- 17865625 TI - LATERAL VENTRAL HERNIA. PMID- 17865626 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held November 1, 1926. PMID- 17865627 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held November 10, 1926. PMID- 17865628 TI - BRIEF COMMUNICATIONS. PMID- 17865629 TI - THE INFLUENCE OF TRADITION IN SURGERY. PMID- 17865630 TI - TREATMENT OF INFECTIONS OF THE FACE. PMID- 17865631 TI - EXPERIENCES WITH THE THYROID PROBLEM IN A DETROIT CLINIC. PMID- 17865632 TI - THYROIDITIS ACCOMPANIED BY HYPERTHYROIDISM. PMID- 17865633 TI - PRIMARY ENDOTHELIOMA OF CERVICAL LYMPH-NODES. PMID- 17865635 TI - UNILOCULAR CYST OF THE SPLEEN. PMID- 17865634 TI - BENIGN TUMORS OF THE STOMACH. PMID- 17865636 TI - TRAUMATIC ABSCESS OF THE SPLEEN. PMID- 17865637 TI - DUODENITIS. PMID- 17865638 TI - USE OF APPENDIX VERMIFORMIS IN THE FORMATION OF A URETHRA IN HYPOSPADIA. PMID- 17865639 TI - SUTURE TECHNIC FOR ABDOMINAL CLOSURE IN CASES OF DRAINAGE. PMID- 17865641 TI - CHRONIC TETANY. PMID- 17865640 TI - THE TREATMENT OF TETANUS. PMID- 17865642 TI - THE PRINCIPLES UNDERLYING THE RATIONAL TREATMENT OF ACUTE OSTEOMYELITIS. PMID- 17865643 TI - FAT NECROSIS OF THE BREAST: A STUDY OF TWENTY CASES. PMID- 17865644 TI - VALUE OF X-RAY IN DIAGNOSIS OF PERFORATED DUODENAL ULCER. PMID- 17865645 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held October 27, 1926. PMID- 17865646 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held November 24, 1926. PMID- 17865647 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held December 6, 1926. PMID- 17865648 TI - THE TREATMENT OF ACID AND ALKALI BURNS: AN EXPERIMENTAL STUDY. PMID- 17865649 TI - CONTRIBUTION TO THE STUDY OF BURNS, THEIR CLASSIFICATION AND TREATMENT. PMID- 17865650 TI - POST-OPERATIVE WATER METABOLISM AND THE INTRADERMAL SALT SOLUTION TEST: A PRELIMINARY REPORT. PMID- 17865651 TI - CHRONIC STRAIN OF THE LUMBAR SPINE AND SACRO-ILIAC JOINTS. PMID- 17865652 TI - FRACTURES OF THE TRANSVERSE PROCESSES OF THE LUMBAR VERTEBRAE. PMID- 17865654 TI - HEPATITIS AND ITS RELATION TO CHOLECYSTITIS. PMID- 17865653 TI - THE USE OF THE RUSSELL APPARATUS IN THE TREATMENT OF FRACTURES OF THE SHAFT OF THE FEMUR. PMID- 17865655 TI - PRE-OPERATIVE AND POST-OPERATIVE TREATMENT OF THE GALL-BLADDER PATIENT. PMID- 17865656 TI - SOME RESULTS OF SURGERY OF THE BILIARY TRACT. PMID- 17865657 TI - FOREIGN BODIES IN THE INTESTINE. PMID- 17865658 TI - THE REPAIR OF INJURIES TO THE POSTERIOR CRUCIAL LIGAMENT OF THE KNEE-JOINT. PMID- 17865659 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held December 8, 1926. PMID- 17865660 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held January 12, 1927. PMID- 17865661 TI - BRIEF COMMUNICATIONS. PMID- 17865662 TI - EXPERIMENTAL RESEARCHES UPON VASOMOTRICITY. PMID- 17865663 TI - SUTURE OF WOUNDS OF THE HEART: WITH REPORT OF A RECENT CASE. PMID- 17865664 TI - PERICARDIAL DECOMPRESSION IN THE TREATMENT OF WOUNDS OF THE HEART AFTER CARDIORRHAPHY. PMID- 17865665 TI - PURULENT PERICARDITIS IN CHILDHOOD. PMID- 17865666 TI - PHLEGMONOUS GASTRITIS. PMID- 17865667 TI - BENIGN HYPERTROPHY OF THE STOMACH AND LINITIS PLASTICA. PMID- 17865669 TI - ACUTE DILATATION OF THE STOMACH OCCURRING UNDER GENERAL ANAESTHESIA. PMID- 17865668 TI - THE EFFECT ON THE JEJUNAL MUCOSA OF TRANSPLANTATION TO THE LESSER CURVATURE OF THE STOMACH. PMID- 17865670 TI - CAUSES OF DEATH FOLLOWING OPERATIONS FOR PERFORATED GASTRIC AND DUODENAL ULCERS. PMID- 17865671 TI - TUMORS OF THE CAECUM: DISCUSSION AND REPORT OF FORTY-EIGHT CASES. PMID- 17865672 TI - THE ADVANTAGES OF A LOW MEDIAN-LINE INCISION IN EXPLORATORY LAPAROTOMY FOR CARCINOMA OF THE RECTUM OR RECTOSIGMOID. PMID- 17865673 TI - CLASSIFICATION OF RENAL AND URETERAL ANOMALIES. PMID- 17865674 TI - SPINAL ANAESTHESIA WITH ANHYDROUS COCAINE: OBSERVATIONS ON 557 ADDITIONAL CASES. PMID- 17865675 TI - THE USE OF REGIONAL ANAESTHESIA BY THE NERVE BLOCK METHOD FOR THE REDUCTION OF FRACTURES AND DISLOCATIONS. PMID- 17865677 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held January 26, 1927. PMID- 17865676 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held January 3, 1927. PMID- 17865678 TI - TRANSTHORACIC ABDOMINAL HERNIA. PMID- 17865680 TI - APPLICATION OF THE PRINCIPLE OF THE QUARANTINE IN ABDOMINAL SURGERY. PMID- 17865679 TI - TRAUMATIC CYANOSIS-ITS PATHOLOGICAL PHYSIOLOGY. PMID- 17865681 TI - ABDOMINAL INCISIONS TREATED BY THE "OPEN METHOD". PMID- 17865682 TI - SURGICAL ANATOMY OF THE RECURRENT LARYNGEAL NERVE WITH ESPECIAL REFERENCE TO THYROID SURGERY. PMID- 17865683 TI - CERVICAL RIB: A METHOD OF ANTERIOR APPROACH FOR RELIEF OF SYMPTOMS BY DIVISION OF THE SCALENUS ANTICUS. PMID- 17865684 TI - BRACHIAL PLEXUS PRESSURE BY THE NORMAL FIRST RIB. PMID- 17865685 TI - PRIMARY ULCER OF THE JEJUNUM. PMID- 17865687 TI - MESENTERIC CYSTS. PMID- 17865686 TI - OBSERVATIONS ON PEPTIC ULCER Continued: IV. PATCH TRANSPLANTS OF JEJUNUM IN THE STOMACH. PMID- 17865688 TI - TUMORS OF TENDON SHEATHS. PMID- 17865689 TI - METACARPAL CENTRAL GIANT-CELL TUMORS. PMID- 17865690 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held February 7, 1927. PMID- 17865691 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY AND THE PHILADELPHIA ACADEMY OF SURGERY Joint Meeting Held February 9, 1927. PMID- 17865692 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held February 23, 1927. PMID- 17865693 TI - BRIEF COMMUNICATIONS. PMID- 17865694 TI - THE RELATIVE VALUE OF THE SPECIAL SENSES. PMID- 17865695 TI - THE PATHOGENESIS AND TREATMENT OF ACUTE EPIPHYSITIS. PMID- 17865696 TI - SECONDARY OPERATIONS ON THE ABDOMEN. PMID- 17865697 TI - THE RECONSTRUCTION OPERATION FOR DEFORMITY SECONDARY TO DISEASE AT THE HIP-JOINT. PMID- 17865698 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 7, 1927: Stated Meeting Held March. PMID- 17865699 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 9, 1927: Stated Meeting Held March. PMID- 17865700 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 23, 1927: Stated Meeting Held March. PMID- 17865701 TI - VALUE OF RADIOGRAPHIC CONTRAST SOLUTIONS IN THE STUDY OF BRAIN ABSCESS. PMID- 17865702 TI - A METHOD OF REMOVING DISCRETE ADENOMATA OF THE THYROID. PMID- 17865703 TI - BILATERAL ATELECTASIS (MASSIVE COLLAPSE) OF LUNG. PMID- 17865704 TI - EMBOLIC AND METASTATIC PHENOMENA IN PLEURAL AND PULMONARY INFECTIONS. PMID- 17865705 TI - SUBCUTANEOUS RUPTURE OF THE LIVER. PMID- 17865707 TI - MEGACOLON. PMID- 17865706 TI - ABDOMINAL SURGERY IN THE PRESENCE OF INFECTION CAUSED BY THE STREPTOCOCCUS HAEMOLYTICUS. PMID- 17865708 TI - MUSCLE-FASCIA SUTURE IN HERNIA. PMID- 17865709 TI - THE PROBLEM OF RECURRENT HERNIA. PMID- 17865710 TI - RECURRENCE AFTER OPERATION FOR OBLIQUE INGUINAL HERNIA IN THE ADULT MALE. PMID- 17865711 TI - THE SURGICAL SIGNIFICANCE OF THE RECTO-SIGMOID SPHINCTER. PMID- 17865712 TI - CHRONIC SYNOVIAL TUBERCULOSIS. PMID- 17865713 TI - THOUGHTS ON THE FUTURE OF THORACIC SURGERY IN AMERICA. PMID- 17865714 TI - THE RELATION OF IMMUNITY TO THE EXPERIMENTAL PRODUCTION OF ABSCESS OF THE LUNG. PMID- 17865715 TI - THE TREATMENT OF PULMONARY SUPPURATION. PMID- 17865716 TI - MECHANICAL PRINCIPLES OF THE OPERATIVE TREATMENT OF PULMONARY TUBERCULOSIS. PMID- 17865717 TI - OPERATIONS AS AIDS IN THE TREATMENT OF PLEUROPULMONARY TUBERCULOSIS. PMID- 17865719 TI - SOME SURGICAL PROBLEMS ATTENDING THE OPERATION OF EXTRAPLEURAL THORACOPLASTY. PMID- 17865718 TI - THE TREATMENT OF SUCH CASES OF CHRONIC SUPPURATIVE BRONCHIECTASIS AS ARE LIMITED TO ONE LOBE OF THE LUNG. PMID- 17865721 TI - THE THORACO-PERITONEAL OPERATION FOR HERNIA OF THE DIAPHRAGM. PMID- 17865720 TI - FURTHER EXPERIENCES WITH INTRA-THORACIC TUMORS. PMID- 17865723 TI - THE PRESENT STATUS OF ANOCIATION: A CRITICAL REVIEW. PMID- 17865724 TI - ETHYLENE AS AN ANAESTHETIC FOR GENERAL SURGERY. PMID- 17865722 TI - THE CHANGING STATUS OF ANAESTHETICS. PMID- 17865725 TI - BLOOD CHANGES UNDER ETHYLENE ANAESTHESIA. PMID- 17865726 TI - ANAESTHESIA IN GENITO-URINARY OPERATIONS. PMID- 17865727 TI - THE ANAESTHETIC PREFERENCES OF AMERICAN SURGEONS: COMPILED FROM REPORTS RECEIVED FROM SIX HUNDRED AND FORTY SURGEONS. PMID- 17865728 TI - OBSERVATIONS ON THE EFFECT OF GLYCOSURIA IN SURGERY. PMID- 17865730 TI - BENIGN STRICTURE OF THE BILE DUCTS. PMID- 17865729 TI - RESULTS OF THE SURGICAL TREATMENT OF CARCINOMA OF THE STOMACH. PMID- 17865731 TI - FRACTURES OF THE EXTERNAL CONDYLE OF THE HUMERUS WITH ROTATION. PMID- 17865732 TI - FRACTURE OF THE FIFTH METATARSAL BONE: WITH SPECIAL REFERENCE TO DELAYED UNION. PMID- 17865733 TI - FINAL RESULTS OF GASTRIC RESECTIONS FOR CANCER. PMID- 17865734 TI - THE COLLOIDAL LEAD TREATMENT OF MALIGNANT NEOPLASMS. PMID- 17865735 TI - MULTIPLE GIANT-CELL TUMORS: REPORT OF A CASE AND REVIEW OF THE LITERATURE. PMID- 17865737 TI - ASEPTIC TECHNIC OF STOMACH RESECTIONS. PMID- 17865736 TI - THE PRINCIPLES UNDERLYING THE SURGERY OF CARCINOMA OF THE RECTUM. PMID- 17865738 TI - PERFORATED ULCERS OF THE DUODENUM: A STUDY OF TWENTY-SEVEN CASES. PMID- 17865739 TI - THE INTERPOSITION OF SMALL BOWEL SEGMENTS BETWEEN DIVIDED ENDS OF THE COLON. PMID- 17865740 TI - FISTULAE OF THE SMALL AND LARGE INTESTINE. PMID- 17865741 TI - EPIGASTRIC HERNIA IN ITS RELATION TO INTRA-ABDOMINAL DISEASE. PMID- 17865742 TI - NOTES ON THE COLLATERAL CIRCULATION IN BLOOD-VESSEL DISEASES OF THE LOWER EXTREMITIES. PMID- 17865743 TI - LIGATION OF THE FEMORAL ARTERY BELOW THE ORIGIN OF THE PROFUNDA FEMORIS IN THE TREATMENT OF OBLITERATIVE ENDARTERITIS OF THE LEG: LEWIS AND REICHERT OPERATION. PMID- 17865744 TI - CIRCULATORY FACTORS INFLUENCING NORMAL OSTEOGENESIS. PMID- 17865745 TI - ANASTOMOSIS OF PORTAL VEIN WITH INFERIOR VENA CAVA: A THOROUGHLY TESTED AND SATISFACTORY METHOD OF MAKING AN ECK FISTULA. PMID- 17865746 TI - THE TREATMENT OF POST-OPERATIVE SUPPURATIVE PAROTIDITIS. PMID- 17865747 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held April 4, 1927. PMID- 17865748 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held April 13, 1927. PMID- 17865750 TI - REPAIR OF HERNIA OF THE DIAPHRAGM. PMID- 17865749 TI - BRIEF COMMUNICATIONS. PMID- 17865751 TI - CHRONIC SUBDURAL HAEMATOMA. PMID- 17865753 TI - THE IMPORTANCE OF RONTGEN EXAMINATIONS IN THE DIAGNOSIS OF FRACTURES OF THE SKULL. PMID- 17865752 TI - ROOT SECTION UNDER LOCAL ANAESTHESIA FOR THE RADICAL CURE OF TRIGEMINAL NEURALGIA MAJOR (TIC DOULOUREUX). PMID- 17865754 TI - EXPERIMENTAL SURGERY OF THE OESOPHAGUS: SOME FACTORS AND END RESULTS. PMID- 17865755 TI - MALIGNANT DISEASE OF THE THYROID GLAND. PMID- 17865757 TI - PHLEGMONOUS GASTRITIS. PMID- 17865756 TI - THE SECONDARY SYMPTOMS OF EXOPHTHALMIC GOITRE (GRAVES' DISEASE). PMID- 17865758 TI - SIDE-TRACKING OPERATIONS FOR BILE DUCT OBSTRUCTION. PMID- 17865759 TI - METASTATIC CARCINOMA IN THE URETER: REPORT OF ADDITIONAL CASES. PMID- 17865760 TI - ENLARGEMENT OF THE PROSTATE GLAND WITH CHARACTERISTICS RESEMBLING HODGKINS' DISEASE: MALIGNANT GRANULOMA. PMID- 17865761 TI - SUSTAINED COUNTERWEIGHT-TRACTION IN HAEMOSTASIS OF PROSTATECTOMY. PMID- 17865762 TI - VITAL FACTORS IN THE MANAGEMENT OF PROSTATIC OBSTRUCTION. PMID- 17865763 TI - GONOCOCCUS EPIDIDYMITIS: OBSERVATIONS IN THREE THOUSAND CASES FROM THE UROLOGICAL SERVICE OF BELLEVUE HOSPITAL. PMID- 17865764 TI - TUBERCULOSIS OF THE KIDNEY IN PREGNANCY. PMID- 17865765 TI - THE PATHOLOGY OF CHARCOT JOINTS. PMID- 17865766 TI - THE PREPARATION OF COLLOIDAL LEAD FOR THERAPEUTIC USE. PMID- 17865767 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held April 27, 1927. PMID- 17865768 TI - BRIEF COMMUNICATIONS. PMID- 17865769 TI - PROGNOSIS AND TREATMENT OF GIANT-CELL SARCOMA: BASED ON A FURTHER STUDY OF END RESULTS IN SIXTY-NINE CASES. PMID- 17865770 TI - THE SURGICAL TREATMENT OF TUBERCULOUS GLANDS OF THE NECK: AN ANALYSIS OF A SERIES OF 140 CASES. PMID- 17865771 TI - TREATMENT OF SURGICAL COLLAPSE OF THE LUNG: A METHOD INVOLVING REMOVING THE FIRST RIB THROUGH THE POSTERIOR TRIANGLE OF THE NECK, AND AT THE SAME TIME, IF DESIRED, AVULSING THE PHRENIC OR POSTERIOR THORACIC NERVE, OR BOTH. PMID- 17865772 TI - THE RESULTS OF OPERATION FOR DUODENAL ULCER IN PHYSICIANS. PMID- 17865773 TI - LATE RESULTS OF OPERATION FOR CARCINOMA OF THE BREAST. PMID- 17865774 TI - TREATMENT OF CARBUNCLES: A COMPARISON OF FOUR DIFFERENT METHODS. PMID- 17865775 TI - GAUCHER'S DISEASE: WITH REPORT OF TWO CASES IN BROTHERS. PMID- 17865776 TI - THE PHENOMENA OF EARLY STAGES IN BONE REPAIR. PMID- 17865778 TI - THE SIMULATION OF GALL-BLADDER DISEASE BY INTERCOSTAL NEURALGIA OF THE ABDOMINAL WALL. PMID- 17865777 TI - THE JOINT COMPLICATIONS OF ACUTE OSTEOMYELITIS OR ACUTE EPIPHYSITIS: AND THE PRINCIPLES UNDERLYING THEIR TREATMENT. PMID- 17865779 TI - ON PYLORIC STENOSIS AS A COMPLICATION IN CHOLELITHIASIS. PMID- 17865781 TI - SACRO-COCCYGEAL CHORDOMA. PMID- 17865780 TI - ACUTE PERFORATION OR RUPTURE OF THE GALL-BLADDER. PMID- 17865782 TI - OBTURATOR HERNIA. PMID- 17865783 TI - ACUTE INFLAMMATION OF DEEP ILIAC LYMPH-NODES. PMID- 17865784 TI - COMPLETE RUPTURE OF INFRA-PATELLA TENDON AND ADJACENT CAPSULAR LIGAMENTS. PMID- 17865785 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held May 2, 1927. PMID- 17865786 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held May 11, 1927. PMID- 17865787 TI - OBSERVATIONS IN THE USE OF CISTERNA MAGNA ESTIMATIONS IN NEUROSURGERY. PMID- 17865789 TI - BULLET FREE IN THE SPINAL CANAL CAUSING DELAYED NEUROLOGICAL MANIFESTATIONS. PMID- 17865788 TI - NEUROGENIC SARCOMA: A CLINICAL AND PATHOLOGICAL STUDY. PMID- 17865790 TI - THE END RESULT IN ALBEE'S OPERATION FOR SPLINTING VERTEBRAE. PMID- 17865791 TI - CHANGES IN BLOOD CONCENTRATION WITH SPECIAL REFERENCE TO THE TREATMENT OF EXTENSIVE SUPERFICIAL BURNS. PMID- 17865792 TI - A NEW EXPLANATION OF THE IMPROVED RESULTS FOLLOWING LIGATION OF BOTH ARTERY AND VEIN. PMID- 17865793 TI - CHRONIC POST-OPERATIVE TETANY. PMID- 17865795 TI - EFFECT OF HYPERTHYROIDISM UPON DIABETES MELLITUS: STRIKING IMPROVEMENT IN DIABETES MELLITUS FROM THYROIDECTOMY. PMID- 17865794 TI - THE USE OF LUGOL'S SOLUTION IN EXOPHTHALMIC GOITRE: AN EXPLANATION FOR THE BENEFICIAL RESULTS OF PRE-OPERATIVE MEDICATION. PMID- 17865796 TI - INTRAPLEURAL PRESSURE IN POST-OPERATIVE ATELECTASIS. PMID- 17865797 TI - CALCULOUS OBSTRUCTION OF THE COMMON AND HEPATIC BILE DUCTS. PMID- 17865799 TI - THE HEALING PROCESS OF GASTRIC ULCER IN MAN. PMID- 17865798 TI - STRANGULATED NON-PARASITIC CYST OF THE LIVER. PMID- 17865800 TI - INGUINAL ENDOMETRIOSIS. PMID- 17865801 TI - TULAREMIA. PMID- 17865802 TI - THE CLINICAL MANIFESTATIONS OF NON-METALLIC PERFORATING INTESTINAL FOREIGN BODIES. PMID- 17865804 TI - BRIEF COMMUNICATIONS. PMID- 17865803 TI - A STUDY OF THE VARIATIONS IN THE TENSILE STRENGTH OF SILK SUTURE MATERIAL. PMID- 17865805 TI - OBSERVATIONS REGARDING VENTRICULAR PUNCTURES. PMID- 17865807 TI - THE USE OF A FLEXED PLASTER SPICA CASE IN THE TREATMENT OF HIP FRACTURES. PMID- 17865806 TI - FORMATION OF RADIUS CONGENITALLY ABSENT: CONDITION SEVEN YEARS AFTER IMPLANTATION OF BONE GRAFT. PMID- 17865808 TI - THE UNTOWARD EFFECTS OF NARCOTICS AND ANAESTHETICS UPON ROBUST AND HANDICAPPED PATIENTS. PMID- 17865809 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held October 10, 1927. PMID- 17865810 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held October 12, 1927. PMID- 17865812 TI - BRIEF COMMUNICATIONS. PMID- 17865811 TI - THE ROLE OF THE DURA MATER IN CRANIAL DECOMPRESSIVE OPERATIONS: A NOTE ON THE PRESERVATION OF THE INNER LAYER OF THE DURA IN CRANIAL DECOMPRESSIVE OPERATIONS, AND ON THE USE OF THE OUTER DURAL LAYER FOR THE PLASTIC CLOSURE OF DURAL DEFECTS. PMID- 17865813 TI - ACQUIRED ARTERIOVENOUS FISTULA. PMID- 17865814 TI - CORONARY DISEASE IN SURGICAL PATIENTS. PMID- 17865815 TI - ASSOCIATION OF HYPERTHYROIDISM WITH DIABETES. PMID- 17865816 TI - CONGENITAL CYSTIC DILATATION OF THE COMMON BILE-DUCT. PMID- 17865817 TI - CHOLANGITIS FOLLOWING CHOLECYSTENTEROSTOMY. PMID- 17865818 TI - CYSTIC LYMPHANGIOMA OF THE GREATER OMENTUM. PMID- 17865819 TI - ABDOMINAL INCISIONS: THEIR MAKING AND CLOSURE. PMID- 17865820 TI - SPONGIOBLASTOMA MULTIFORME OF THE BRAIN. PMID- 17865821 TI - THE De PETZ STOMACH AND INTESTINAL SUTURING APPARATUS. PMID- 17865822 TI - CARCINOMA OF THE OVARY IN INFANCY. PMID- 17865823 TI - ACID AND ALKALI BURNS OF THE EYE: AN EXPERIMENTAL STUDY. PMID- 17865824 TI - INDELIBLE INK-PENCIL INJURIES. PMID- 17865826 TI - COLONIC ANAESTHESIA IN OPERATIONS UPON BRAIN AND SPINAL CORD. PMID- 17865825 TI - CHROMOMA OF THE FOREARM: A STUDY OF AN UNUSUAL TUMOR. PMID- 17865828 TI - THE RELIEF OF PAIN IN CARCINOMA OF THE FACE. PMID- 17865827 TI - DIFFERENTIAL SECTION OF THE TRIGEMINAL ROOT IN THE SURGICAL TREATMENT OF TRIGEMINAL NEURALGIA. PMID- 17865829 TI - BRANCHIAL ANOMALIES AND NEOPLASMS: A REPORT OF THIRTY-TWO CASES WITH FOLLOW-UP RESULTS. PMID- 17865830 TI - CERTAIN EFFECTS OF OBSTRUCTION OF THE BILE DUCTS. PMID- 17865831 TI - GASTROJEJUNAL ULCERS AND GASTROJEJUNOCOLIC FISTULAE. PMID- 17865832 TI - PROGRESSIVE GANGRENOUS ULCERATION OF THE ABDOMINAL WALL. PMID- 17865834 TI - POSTERIOR EXCISION OF THE SEMINAL VESICLES. PMID- 17865833 TI - SOLITARY CYSTS OF THE KIDNEY. PMID- 17865835 TI - MALIGNANT TUMORS OF THE TESTICLE. PMID- 17865836 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held October 26, 1927. PMID- 17865837 TI - TRANASACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held November 9, 1927. PMID- 17865839 TI - BRIEF COMMUNICATIONS. PMID- 17865838 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held November 7, 1927. PMID- 17865840 TI - THE TREATMENT OF COMPOUND INJURIES OF THE EXTREMITIES. PMID- 17865841 TI - HEAD INJURIES IN CHILDREN: AN ANALYSIS OF 331 CASES WITH ESPECIAL REFERENCE TO END RESULTS. PMID- 17865842 TI - THE USE OF VISOR FLAPS FROM THE CHEST IN PLASTIC OPERATIONS UPON THE NECK, CHIN AND LIP. PMID- 17865843 TI - MALIGNANT DISEASE OF THE THYROID GLAND: A CLINICAL CONSIDERATION. PMID- 17865844 TI - TONSILLECTOMY WITH BLOODLESS TECHNIC. PMID- 17865846 TI - SOME UNDERLYING PRINCIPLES OF INTESTINAL SURGERY. PMID- 17865845 TI - PRIMARY SARCOMA OF THE CLAVICLE. PMID- 17865847 TI - PROPHYLACTIC GASTROSTOMY. PMID- 17865848 TI - OBSERVATIONS ON PEPTIC ULCER Continued: V. FINDINGS IN EXPERIMENTALLY PRODUCED PEPTIC ULCER: ETIOLOGIC AND THERAPEUTIC CONSIDERATIONS. PMID- 17865849 TI - TREATMENT OF ACUTE CHOLECYSTITIS. PMID- 17865850 TI - POINTS IN THE TECHNIC OF OPERATIVE REMOVAL OF KIDNEY STONES. PMID- 17865851 TI - CYSTOSCOPY REACTIONS. PMID- 17865852 TI - THE ABDUCTION TREATMENT, A STANDARD PROCEDURE FOR ALL FORMS OF FRACTURE AT THE HIP-JOINT. PMID- 17865853 TI - SUSPENSION OF THE FOOT IN TREATMENT OF POTT'S FRACTURE WITH PERSISTENT POSTERIOR DISLOCATION OF ASTRAGALUS. PMID- 17865854 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held November 23, 1927. PMID- 17865855 TI - BRIEF COMMUNICATIONS. PMID- 17865856 TI - SUTURE OF THE RECURRENT LARYNGEAL NERVE FOR BILATERAL ABDUCTOR PARALYSIS. PMID- 17865857 TI - TREATMENT OF SUPPURATION OF THE LUNG. PMID- 17865858 TI - OBLITERATIVE OPERATIONS FOR MASSIVE EMPYEMA. PMID- 17865860 TI - ACUTE SUBPECTORAL ABSCESS. PMID- 17865859 TI - POSTERIOR MEDIASTINAL ABSCESS FOLLOWING SUPPURATIVE ARTHRITIS OF CERVICAL VERTEBRAE. PMID- 17865861 TI - PULMONARY EMBOLISM. PMID- 17865862 TI - HARELIP AND CLEFT-PALATE: A STUDY OF FOUR HUNDRED AND TWENTY-FIVE CONSECUTIVE CASES. PMID- 17865863 TI - PSEUDO-CARCINOMA OF THE STOMACH: SOME UNUSUAL LESIONS OF THE STOMACH RESEMBLING CARCINOMA. PMID- 17865864 TI - TREATMENT OF ULCER OF THE STOMACH AND DUODENUM: A PLAN BASED ON THE CLASSIFICATION OF PATHOLOGIC TYPES. PMID- 17865866 TI - GASTRO-JEJUNO-COLIC FISTULA: AN UNUSUAL AND FATAL COMPLICATION FOLLOWING OPERATIONS FOR DUODENAL ULCER. PMID- 17865865 TI - INTUSSUSCEPTION OF THE SMALL INTESTINE INTO STOMACH THROUGH A GASTRO-ENTEROSTOMY STOMA. PMID- 17865867 TI - SURGICAL INTERVENTION IN EXTRA-UTERINE PREGNANCY: OBSERVATIONS IN THE TREATMENT OF 109 CASES AT THE PENNSYLVANIA HOSPITAL. PMID- 17865869 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY Stated Meeting Held December 5, 1927. PMID- 17865868 TI - FRENCH-HEEL FRACTURES OF THE TARSAL SCAPHOID. PMID- 17865871 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held January 11, 1928. PMID- 17865870 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY Stated Meeting Held December 14, 1927. PMID- 17865872 TI - BRIEF COMMUNICATIONS. PMID- 17865873 TI - THROMBOPHLEBITIS OF THE LOWER EXTREMITIES. PMID- 17865874 TI - EMBOLECTOMY: REPORT OF THREE CASES. PMID- 17865875 TI - ARTERIAL EMBOLECTOMY. PMID- 17865877 TI - SUBLINGUAL PHLEGMON: PRIMARY AND SECONDARY LUDWIG'S ANGINA. PMID- 17865876 TI - ILEOCAECAL ENTEROCYSTOMA PRODUCING PARTIAL INTUSSUSCEPTION. PMID- 17865878 TI - ULCERATIVE COLITIS. PMID- 17865880 TI - ABDOMINAL INJURIES IN CHILDREN. PMID- 17865879 TI - A NEW TYPE OF PERMANENT COLOSTOMY. PMID- 17865881 TI - OPERATIVE MORTALITY AND END RESULTS IN GALL-BLADDER SURGERY. PMID- 17865882 TI - DIVERTICULA OF THE BLADDER: REMARKS FOUNDED UPON A STUDY OF TWELVE CASES. PMID- 17865884 TI - HODGKIN'S DISEASE OF BONES. PMID- 17865883 TI - CONGENITAL HYPERTROPHY OF THE INTERURETERAL RIDGE. PMID- 17865886 TI - THE PROPHYLAXIS OF GAS GANGRENE IN CIVIL SURGERY. PMID- 17865885 TI - PUERPERAL GANGRENE OF THE EXTREMITIES. PMID- 17865888 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY STATED MEETING HELD JANUARY 16, 1928. PMID- 17865887 TI - THE TECHNIC OF BLOOD TRANSFUSION. PMID- 17865889 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD JANUARY 25, 1928. PMID- 17865891 TI - BLOOD FROM TRAUMATIZED LIMBS. PMID- 17865890 TI - EPINEPHRECTOMY (ADRENALECTOMY) FOR HYPERADRENALINEMIA. PMID- 17865892 TI - SPINA BIFIDA AND CRANIAL MENINGOCELE. PMID- 17865893 TI - HEART INJURIES-WITH SUTURE. PMID- 17865894 TI - PRIMARY HYPERNEPHROMA OF THE LIVER. PMID- 17865896 TI - NON-PARASITIC CYSTS OF THE LIVER. PMID- 17865895 TI - REMOTE RESULTS OF BILIARY SURGERY. PMID- 17865897 TI - PHLEGMONOUS GASTRITIS: OF BACILLUS AEROGENES CAPSULATUS (B. WELCHII) ORIGIN. PMID- 17865898 TI - LATE RESULTS IN PERFORATED AND GASTRO-DUODENAL ULCERS. PMID- 17865899 TI - ASEPTIC END-TO-END INTESTINAL ANASTOMOSIS. PMID- 17865900 TI - ACUTE INFLAMMATORY OBSTRUCTION OF TERMINAL ILEUM. PMID- 17865901 TI - FIBROMATA OF THE MESENTERY. PMID- 17865902 TI - LYMPHANGIOMA OF OMENTUM. PMID- 17865903 TI - LYMPHOSARCOMA OF THE MESENTERY. PMID- 17865904 TI - BRACHIAL PLEXUS ANAESTHESIA: ITS INDICATIONS, TECHNIQUE, AND DANGERS. PMID- 17865905 TI - TRAUMATIC OSTEOPOROSIS OF THE CARPAL BONES. PMID- 17865906 TI - DERANGEMENTS OF THE KNEE-JOINT. PMID- 17865907 TI - MELANOTIC TUMORS: NONMELANOTIC MELANO-EPITHELIOMAS AND THEIR RELATION TO THE MELANO-EPITHELIOMAS. PMID- 17865908 TI - MALIGNANT LYMPHOCYTOMA. PMID- 17865909 TI - RECURRENT FIBROMATOUS TUMORS OF THE SKIN. PMID- 17865911 TI - Critique on Adrenalectomy for Alleged Hyperadrenalinemia. PMID- 17865910 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 22, 1928: Stated Meeting Held February. PMID- 17865912 TI - SURGERY OF THE PITUITARY LESION. PMID- 17865913 TI - GENESIS, MORPHOLOGY, AND SURGERY OF PROSTATIC MIDDLE LOBE HYPERTROPHY. PMID- 17865914 TI - CLOSURE OF THE PROSTATIC BED IN SUPRA-PUBIC PROSTATECTOMY. PMID- 17865916 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY AND THE NEW YORK SURGICAL SOCIETY Conjoint Meeting Held February 8, 1928. PMID- 17865915 TI - XANTHOMA OF THE NECK. PMID- 17865917 TI - STUDIES ON EXPERIMENTAL PULMONARY ATELECTASIS: 1. THE PRODUCTION OF ATELECTASIS. PMID- 17865919 TI - THE DUODENAL TUBE AS AN AID IN THE SURGICAL TREATMENT OF EXOPHTHALMIC GOITRE: PRELIMINARY REPORT OF THIRTY CASES. PMID- 17865918 TI - BRIEF COMMUNICATIONS. PMID- 17865920 TI - THE THERAPEUTIC VALUE OF IRRADIATION IN THE TREATMENT OF MAMMARY CANCER: A SURVEY OF FIVE-YEAR RESULTS IN 355 CASES TREATED AT THE MEMORIAL HOSPITAL OF NEW YORK. PMID- 17865922 TI - OPERATIVE RELIEF OF CARDIOSPASM WHERE DILATATION HAS FAILED. PMID- 17865921 TI - GASTROSTOMY IN CARCINOMA OF THE OESOPHAGUS. PMID- 17865923 TI - POST-OPERATIVE PULMONARY ATELECTASIS. PMID- 17865924 TI - MORTALITY FACTORS IN ACUTE APPENDICITIS. PMID- 17865925 TI - THE GIBSON-MIKULICZ DRAIN IN ACUTE APPENDICITIS: WITH REPORT OF 1588 CASES. PMID- 17865926 TI - CONGENITAL ABSENCE OF THE GALL-BLADDER. PMID- 17865927 TI - LYMPHOID HYPERPLASIA OF LACRYMAL AND SALIVARY GLANDS: MIKULICZ' DISEASE. PMID- 17865928 TI - THE SURGICAL PATHOLOGY OF EPIDIDYMITIS. PMID- 17865929 TI - MASSIVE (ATELECTATIC) COLLAPSE OF THE LUNG. PMID- 17865930 TI - SURGICAL LESIONS OF THE BILIARY TRACT. PMID- 17865931 TI - CLOSURE OF THE ABDOMEN WITHOUT DRAINAGE AFTER OPERATIONS UPON THE BILE TRACTS. PMID- 17865932 TI - HIDDEN PERFORATION OF THE GALL-BLADDER. PMID- 17865934 TI - SPONTANEOUS RUPTURE OF SPLEEN WITH VENOUS THROMBOSIS. PMID- 17865933 TI - LATE INTESTINAL STENOSIS FOLLOWING STRANGULATED HERNIA. PMID- 17865935 TI - ANALYSIS OF ONE HUNDRED AND SEVENTY-SIX CASES OF CARCINOMA OF THE STOMACH SUBMITTED TO AUTOPSY. PMID- 17865936 TI - AN EXPERIMENTAL STUDY OF ARTERIAL COLLATERAL CIRCULATION. PMID- 17865937 TI - TEMPERATURE EFFECT OF POPLITEAL VEIN LIGATION IN THROMBO-ANGIITIS OBLITERANS AND ARTERIOSCLEROSIS. PMID- 17865938 TI - PRIMARY BILATERAL TUMORS OF THE TESTICLE. PMID- 17865939 TI - PHAGEDAENIC ULCERATION OF THE SKIN. PMID- 17865940 TI - FRACTURE AND DISLOCATION OF THE STERNUM: REPORT OF THREE CASES. PMID- 17865941 TI - TREATMENT OF FRACTURES INVOLVING THE ANKLE-JOINT: WITH SPECIAL REFERENCE TO THE USE OF THE PILLOW SPLINT AND EARLY WEIGHT-BEARING. PMID- 17865942 TI - END RESULTS OF CARPALECTOMY. PMID- 17865943 TI - ACUTE HAEMATOGENOUS OSTEOMYELITIS: THE RELATIONSHIP OF ITS PATHOLOGY TO PROGNOSIS AND TREATMENT. PMID- 17865945 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD MARCH 14, 1928. PMID- 17865944 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY STATED MEETING HELD MARCH 5, 1928. PMID- 17865946 TI - BRIEF COMMUNICATIONS. PMID- 17865947 TI - ADDRESS OF THE PRESIDENT: EARLY HISTORY OF MEDICAL EDUCATION IN CALIFORNIA. PMID- 17865948 TI - SOME FUNDAMENTAL CHARACTERISTICS OF THE SPLEEN AND THEIR RELATION TO FUNCTION. PMID- 17865949 TI - DEVELOPMENT AND PROGRESS OF SURGERY OF THE SPLEEN. PMID- 17865950 TI - SURGICAL TECHNIC OF SPLENECTOMY WITH PRESENTATION OF NEW INCISION. PMID- 17865951 TI - SPLENIC ENLARGEMENT WITH CIRRHOSIS OF THE LIVER: BANTI'S SYNDROME. PMID- 17865952 TI - UNCLASSIFIED TYPE OF SPLENOMEGALY IN CHILDREN. PMID- 17865953 TI - ATYPICAL HAEMOLYTIC ANEMIA WITH SPLENOMEGALY IN CHILDREN. PMID- 17865954 TI - SPLENECTOMY FOR TRAUMA. PMID- 17865956 TI - A REVIEW OF 500 SPLENECTOMIES WITH SPECIAL REFERENCE TO MORTALITY AND END RESULTS. PMID- 17865955 TI - SPLENECTOMY: REPORT OF A CASE WITH PATHOLOGY UNCLASSIFIED. PMID- 17865957 TI - ABSCESS OF THE SPLEEN. PMID- 17865959 TI - SURGERY OF THE SYMPATHETIC SYSTEM. INDICATIONS AND RESULTS. PMID- 17865958 TI - SPLENECTOMY IN EGYPT. PMID- 17865960 TI - CLINICAL STUDIES OF ADRENALECTOMY AND SYMPATHECTOMY. PMID- 17865961 TI - END RESULTS OF PERIARTERIAL SYMPATHECTOMY. PMID- 17865962 TI - LUMBAR SYMPATHETIC GANGLIONECTOMY AND RAMISECTOMY FOR CONGENITAL IDIOPATHIC DILATATION OF THE COLON. PMID- 17865963 TI - EFFECT OF SYMPATHECTOMY UPON THE PAIN OF ORGANIC DISEASE OF ARTERIES OF THE LOWER LIMBS AND FOR OBSCURE ABDOMINAL PAIN. PMID- 17865965 TI - OPERATION FOR THE RADICAL CURE OF TRIGEMINAL NEURALGIA: ANALYSIS OF FIVE HUNDRED CASES. PMID- 17865964 TI - TUMORS OF THE AUTONOMIC NERVOUS SYSTEM. PMID- 17865966 TI - RECURRING ULCERS FOLLOWING PARTIAL GASTRECTOMY. PMID- 17865968 TI - PYLORIC ACHALASIA AND PEPTIC ULCER. PMID- 17865967 TI - CANCER OF THE STOMACH IN PATIENTS OVER SEVENTY YEARS OF AGE. PMID- 17865969 TI - THE DILATED DUODENUM. PMID- 17865970 TI - THE VALUE OF THE RECTAL TUBE IN OPERATIONS FOR ACUTE ABDOMINAL CONDITIONS. PMID- 17865971 TI - RESECTION OF THE PANCREAS. PMID- 17865972 TI - INTERPOSITION OF A LOOP OF ILEUM TO REPAIR DEFECTS IN THE COLON. PMID- 17865973 TI - THE MIKULICZ OPERATION FOR RESECTION OF THE COLON: ITS ADVANTAGES AND DANGERS. PMID- 17865975 TI - TRAUMATIC EMPHYSEMA. PMID- 17865974 TI - INTRATHORACIC DERMOIDS: WITH THE REPORT OF A CASE OF TOTAL EXTIRPATION AT ONE SITTING BY A NEW METHOD OF THORACOTOMY. PMID- 17865976 TI - END RESULTS IN HODGKIN'S DISEASE AND LYMPHOSARCOMA TREATED BY THE MIXED TOXINS OF ERYSIPELAS AND BACILLUS PRODIGIOSUS, ALONE OR COMBINED WITH RADIATION. PMID- 17865978 TI - DIVISION OF THE VAGI FOR PYLOROSPASM. PMID- 17865977 TI - HAEMANGIOMA OF CHEST WALL. PMID- 17865979 TI - THE PERITONEUM AS RELATED TO PERITONITIS: AN EXPERIMENTAL STUDY. PMID- 17865980 TI - CHRONIC APPENDICITIS. PMID- 17865981 TI - BEZOARS: WITH THE REPORT OF AN ADDITIONAL CASE OF PHYTOBEZOAR. PMID- 17865982 TI - ADAMANTINOMA. PMID- 17865983 TI - CANCER IN AND ABOUT THE MOUTH: A STUDY OF TWO HUNDRED AND ELEVEN CASES. PMID- 17865984 TI - JUVENILE GANGRENE. PMID- 17865985 TI - NON-UNION OF FRACTURES: AN EXPERIMENTAL AND CLINICAL STUDY. PMID- 17865986 TI - THE EDUCATIONAL VALUE OF THE FOLLOW-UP: A REPORT OF 14 YEARS-FROM THE FIRST SURGICAL DIVISION (CORNELL MEDICAL) OF THE NEW YORK HOSPITAL. PMID- 17865987 TI - ROBERT ABBE 1851-1928. PMID- 17865989 TI - SUPPURATIVE PERICARDITIS FROM THE SURGICAL VIEWPOINT. PMID- 17865988 TI - CONGENITAL BILATERAL HALLUX VALGUS. PMID- 17865990 TI - PULMONARY ABSCESS-AN EXPERIMENTAL STUDY. PMID- 17865991 TI - VASOMOTOR AND REFLEX SEQUELAE OF UNILATERAL CERVICAL AND LUMBAR RAMISECTOMY IN A CASE OF RAYNAUD'S DISEASE, WITH OBSERVATIONS ON TONUS. PMID- 17865992 TI - RESULTS OF DELAY IN TREATMENT OF BREAST CANCER. PMID- 17865993 TI - THE HAEMORRHAGIC DIATHESIS OF OBSTRUCTIVE JAUNDICE AND ITS TREATMENT. PMID- 17865994 TI - BENIGN TUMORS OF THE STOMACH. PMID- 17865995 TI - FASCIAL SUTURES FOR INGUINAL HERNIA. PMID- 17865996 TI - FURTHER EXPERIENCES WITH PURELY FASCIAL HERNIOTOMY. PMID- 17865997 TI - THE INTERNAL FIXATION OF FRACTURES AND DISLOCATIONS BY USE OF THE HUMAN FASCIAL SUTURE. PMID- 17865998 TI - AINHUM. PMID- 17865999 TI - A STUDY OF 520 CASES OF FRACTURES OF THE SKULL. PMID- 17866001 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD MARCH 28, 1928. PMID- 17866000 TI - FRACTURE OF THE NECK OF THE FEMUR IN CHILDHOOD: A REPORT OF SIX CASES. PMID- 17866002 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD APRIL 11, 1928. PMID- 17866003 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY STATED MEETING HELD APRIL 2, 1928. PMID- 17866004 TI - BRIEF COMMUNICATIONS. PMID- 17866005 TI - CANCER OF THE TONGUE AND FLOOR OF THE MOUTH. PMID- 17866006 TI - DEEP PULSION DIVERTICULA OF OESOPHAGUS. PMID- 17866008 TI - SPINDLE-CELLED SARCOMA OF THE KIDNEY IN ADULTS. PMID- 17866007 TI - PRIMARY EXTRARENAL HYPERNEPHROMA. PMID- 17866009 TI - CONGENITAL ABSENCE OF ONE KIDNEY: UNILATERAL RENAL AGENESIS. PMID- 17866011 TI - SUPERNUMERARY ECTOPIC URETERS. PMID- 17866010 TI - KIDNEY RESECTION. PMID- 17866012 TI - THE ETIOLOGICAL RELATIONSHIP OF CHRONIC APPENDICITIS AND THE SMALL CYSTIC OVARY: BASED ON A STUDY OF 256 CASES. PMID- 17866013 TI - ADENOCARCINOMA OF THE TESTIS IN THE ADULT. PMID- 17866014 TI - CARCINOMA OF THE TESTICLE. PMID- 17866016 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY STATED MEETING HELD MAY 14, 1928. PMID- 17866015 TI - ORCHIDOPEXY FOR VARICOCELE: A METHOD FOR TREATING VARICOCELE BY MEANS OF LIVING TISSUE. PMID- 17866017 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD MAY 9, 1928. PMID- 17866019 TI - MYELOMA OF THE SPINE. PMID- 17866018 TI - ANTI-STAPHYLOCOCCIC EFFECTS OF THE INTRAARTERIAL INJECTION OF CERTAIN DYES: REPORT OF INTRAARTERIAL INJECTIONS OF MERCUROCHROME 220-SOLUBLE; GENTIAN VIOLET, AND ACRIFLAVINE IN THE TREATMENT OF EXPERIMENTAL STAPHYLOCOCCIC INFECTIONS IN DOGS. PMID- 17866020 TI - TRANSBUCCAL APPROACH TO THE ENCEPHALON: IN EXPERIMENTAL OPERATIONS UPON CARNIVORAL PITUITARY, PONS, AND VENTRAL MEDULLA. PMID- 17866021 TI - PLASTIC SURGERY ABOUT THE EYES. PMID- 17866022 TI - CONGENITAL ANOMALIES OF THE DUODENUM WITH OBSTRUCTION AT THE DUODENOJEJUNAL ANGLE. PMID- 17866023 TI - A CONTRIBUTION TO THE MECHANISM OF FRACTURES AND DISLOCATIONS IN THE ELBOW REGION. PMID- 17866025 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY STATED MEETING HELD OCTOBER 1, 1928. PMID- 17866024 TI - TUMORS WHICH MAY EXPAND THE CURVATURE OF THE DUODENUM, PARTICULARLY TUMORS AND INFECTIONS OF THE RETROPERITONEAL LYMPH NODES. PMID- 17866026 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD OCTOBER 10, 1928. PMID- 17866027 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD OCTOBER 24, 1928. PMID- 17866028 TI - BENIGN TUMORS OF THE DUODENUM. PMID- 17866030 TI - AFFECTIONS OF THE APPENDIX IN YOUNG CHILDREN: A REVIEW OF 100 CASES. PMID- 17866029 TI - DUODENAL DIVERTICULA AND THEIR SURGICAL TREATMENT. PMID- 17866031 TI - MALIGNANCIES OF THE COLON. PMID- 17866032 TI - ATRESIA OF THE DUODENUM AND DUODENAL DIVERTICULA. PMID- 17866033 TI - MORTALITY FOLLOWING COLOSTOMY FOR CARCINOMA OF THE LARGE BOWEL. PMID- 17866034 TI - THE CARE OF THE COLOSTOMY. PMID- 17866036 TI - A STUDY OF THREE HUNDRED FORTY-THREE SURGICAL CASES OF INTESTINAL OBSTRUCTION. PMID- 17866035 TI - CARCINOMA OF THE RECTUM AND RECTO-SIGMOID. PMID- 17866037 TI - THE FUTURE OF SURGERY. PMID- 17866039 TI - VALUE OF METHYLENE BLUE-GENTIAN VIOLET 5 PER CENT. IN PREOPERATIVE SKIN PREPARATION. PMID- 17866038 TI - THE BIOLOGICAL EFFECTS OF THE X-RAY AND RADIUM AS AN AID IN THE DIAGNOSIS OF NEOPLASTIC DISEASES. PMID- 17866041 TI - ALCOHOL INJECTION IN ANGINA PECTORIS. PMID- 17866040 TI - THE ALCOHOLIZED NERVE GRAFT: AN EXPERIMENTAL STUDY. PMID- 17866042 TI - THE MORTALITY OF OPERATIONS UPON THE THYROID GLAND: WITH AN ANALYSIS OF 388 OPERATIONS PERFORMED DURING 1927. PMID- 17866044 TI - MESENTERIC INJURIES AND INTESTINAL VIABILITY. PMID- 17866043 TI - PERFORATION OF PEPTIC ULCER: OBSERVATION OF ONE HUNDRED CASES AT THE PENNSYLVANIA AND PRESBYTERIAN HOSPITALS. PMID- 17866045 TI - THE INTERPRETATION OF CHOLECYSTOGRAPHIC FINDINGS: OPERATIVE CHECK IN TWO HUNDRED AND SEVENTY-SEVEN CASES. PMID- 17866046 TI - RELIEF OF OBSTRUCTIVE JAUNDICE FROM TUMORS IN THE HEAD OF THE PANCREAS. PMID- 17866047 TI - SUBCUTANEOUS RUPTURE OF THE STOMACH; TRAUMATIC AND SPONTANEOUS. PMID- 17866048 TI - RUPTURED GASTRODUODENAL ULCER: A REPORT OF TWENTY-SEVEN CASES. PMID- 17866049 TI - MYOMA OF THE APPENDIX. PMID- 17866050 TI - PRIMARY CARCINOMA OF THE VERMIFORM APPENDIX. PMID- 17866051 TI - APPENDECTOMY WOUND REPAIR AND HERNIA. PMID- 17866052 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD APRIL 25, 1928. PMID- 17866053 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY STATED MEETING HELD NOVEMBER 5, 1928. PMID- 17866054 TI - THE HARPANAHALLI BEZOAR. PMID- 17866055 TI - FREDERIC KAMMERER 1856-1928. PMID- 17866056 TI - HOWARD A. LOTHROP 1864-1928. PMID- 17866058 TI - SURGICAL TECHNIC. PMID- 17866057 TI - SYPHILIS AND SURGERY. PMID- 17866060 TI - WHEN AND WHEN NOT TO OPEN THE ABDOMEN IN ACUTE SURGICAL CONDITIONS. PMID- 17866059 TI - TRAUMATIC FACIAL PARALYSIS AND ITS SURGICAL TREATMENT BY FREE TRANSPLANTATION OF FASCIA LATA. PMID- 17866061 TI - THE TREATMENT OF INTESTINAL OBSTRUCTION. PMID- 17866063 TI - STRICTURE OF THE MALE URETHRA. PMID- 17866062 TI - AN ANATOMICAL AND CLINICAL STUDY OF INFECTIONS OF THE HAND. PMID- 17866064 TI - URETHRAL STONES. PMID- 17866066 TI - ASTRAGALO-SCAPHOID DISLOCATION. PMID- 17866065 TI - EXTRAARTICULAR ARTHRODESIS OF THE HIP FOR TUBERCULOSIS: WITH A REPORT OF 31 CASES. PMID- 17866067 TI - ASTRAGALECTOMY FOR FRACTURES OF THE ASTRAGALUS. PMID- 17866068 TI - ACUTE FRACTURE-DISLOCATIONS ABOUT THE ANKLE JOINT. PMID- 17866069 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 14, 1928: Stated Meeting Held November. PMID- 17866070 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 3, 1928: Stated Meeting Held December. PMID- 17866071 TI - BRIEF COMMUNICATIONS. PMID- 17866073 TI - DIAPHRAGMATIC HERNIA: REPAIR BY TWO-STAGE OPERATION EMPLOYING PRELIMINARY EXTRA PLEURAL THORACOPLASTY. PMID- 17866072 TI - PULMONARY INFARCTION AND EMBOLISM. PMID- 17866074 TI - THE NORMAL THICKNESS OF THE PYLORIC MUSCLE AND THE INFLUENCE ON IT OF ULCER, GASTRO-ENTEROSTOMY AND CARCINOMA. PMID- 17866075 TI - PERFORATED PEPTIC ULCER. PMID- 17866076 TI - ACUTE INFLAMMATION OF MECKEL'S DIVERTICULUM. PMID- 17866077 TI - THE MORTALITY OF INTESTINAL OBSTRUCTION: ANALYSIS OF 124 CASES OPERATED UPON AT THE HOSPITAL OF THE UNIVERSITY OF PENNSYLVANIA. PMID- 17866079 TI - BONE CHANGES IN GAUCHER'S SPLENOMEGALY. PMID- 17866078 TI - BILATERAL ADENOCARCINOMA OF THE BREAST. PMID- 17866080 TI - OSTEOMYELITIS OF THE VERTEBRAE. PMID- 17866081 TI - OSTEOPOROSIS OF THE HUMERUS FOLLOWING FRACTURE. PMID- 17866082 TI - ON THE TREATMENT OF THE SEPARATION OF THE LOWER EPIPHYSIS OF THE FEMUR. PMID- 17866083 TI - FRACTURES OF THE TIBIA INVOLVING THE KNEE. PMID- 17866084 TI - THE TREATMENT OF DIFFICULT FRACTURES OF BOTH BONES OF THE LEG. PMID- 17866085 TI - VALUE OF CLOSING COMPOUND FRACTURES BY SKIN PLASTIC. PMID- 17866087 TI - THE TREATMENT OF SUPRACONDYLAR FRACTURE OF THE HUMERUS. PMID- 17866086 TI - THE TREATMENT OF FRACTURES OF THE CLAVICLE: A STUDY OF 422 CASES OBSERVED IN THE OUT-PATIENT DEPARTMENT OF THE ROOSEVELT HOSPITAL OF THE CITY OF NEW YORK. PMID- 17866088 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD NOVEMBER 28, 1928. PMID- 17866089 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY STATED MEETING HELD JANUARY 8, 1929. PMID- 17866090 TI - BRIEF COMMUNICATIONS. PMID- 17866091 TI - THE USE OF BACILLUS WELCHII (PERFRINGENS) ANTITOXIN IN EXPERIMENTAL GENERAL PERITONITIS AND INTESTINAL OBSTRUCTION. PMID- 17866092 TI - THE ROLE OF THE BACILLUS WELCHII IN ACUTE INTESTINAL OBSTRUCTION: WITH LIGATION OF THE VEINS TO THE OBSTRUCTED LOOP. PMID- 17866093 TI - SOME CLINICAL FINDINGS IN SUBTOTAL GASTRECTOMY. PMID- 17866094 TI - URETERO-ENTEROVENTRAL FISTULA. PMID- 17866095 TI - EXTENSIVE RESECTIONS OF THE SMALL INTESTINE. PMID- 17866097 TI - PRIMARY EPITHELIOMA OF THE VULVA: AN ANALYSIS OF SEVENTY-ONE CASES. PMID- 17866096 TI - THE DIAGNOSIS OF PRIMARY NEOPLASMS OF THE RENAL PELVIS. PMID- 17866099 TI - CARPAL OSTEITIS. PMID- 17866098 TI - OSTEOMYELITIS OF THE VERTEBRAE. PMID- 17866100 TI - FRACTURE OF THE CARPAL SCAPHOID. PMID- 17866101 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD DECEMBER 12, 1928. PMID- 17866102 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD JANUARY 9, 1929. PMID- 17866104 TI - THE USE OF IODIZED RAPE-SEED OIL (CAMPIODOL) FOR RONTGENOGRAPHIC EXPLORATION. PMID- 17866103 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD JANUARY 23, 1929. PMID- 17866105 TI - NON-UNION OF FRACTURES: AN EXPERIMENTAL STUDY. PMID- 17866106 TI - THE EFFECT OF IODINE AND THYROID FEEDING ON THE THYROID GLAND. PMID- 17866107 TI - EFFECT OF ABDOMINAL THERMAL APPLICATIONS ON THE INTRAPERITONEAL TEMPERATURE. PMID- 17866108 TI - BILE PERITONITIS AND BILE ASCITES. PMID- 17866109 TI - SAFETY FACTORS IN MESENTERIC LIGATIONS. PMID- 17866110 TI - THE FATE OF THE FREE OMENTAL GRAFT IN ABDOMINAL SURGERY. PMID- 17866111 TI - THE SMALL DEEP GRAFT: RELATIONSHIP TO THE TRUE REVERDIN GRAFT. PMID- 17866113 TI - TWO CASES OF SUTURE OF STAB WOUNDS OF THE HEART. PMID- 17866112 TI - IMPRESSIONS RESULTING FROM THREE THOUSAND TRANSFUSIONS OF UNMODIFIED BLOOD. PMID- 17866114 TI - END RESULTS OF SURGERY OF THE BILIARY TRACT: A STUDY OF 634 CASES TREATED AT THE LAHEY CLINIC. PMID- 17866116 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY STATED MEETING HELD FEBRUARY 4, 1929. PMID- 17866115 TI - TREATMENT OF BILIARY FISTULA BY DIRECT IMPLANTATION OF THE TRACT INTO THE FIRST PORTION OF THE DUODENUM. PMID- 17866118 TI - RECONSTRUCTION OF THE HIP-JOINT IN CONGENITAL DISLOCATIONS. PMID- 17866117 TI - MALIGNANT EPITHELIAL TUMORS OF THE NECK OF UNKNOWN ORIGIN. PMID- 17866119 TI - TRANSPLANTATION OF URETERS FOR IRREPARABLE BLADDER INJURY. PMID- 17866121 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY AND THE PHILADELPHIA ACADEMY OF SURGERY 13, 1929: Joint Meeting Held February. PMID- 17866120 TI - BRANCHIAL CYSTS OF THE PAROTID GLAND. PMID- 17866122 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 27, 1929: Stated Meeting Held February. PMID- 17866123 TI - THE MANAGEMENT OF INTRA-ORAL CANCERS AT THE RADIUM INSTITUTE OF THE UNIVERSITY OF PARIS. PMID- 17866124 TI - BRIEF COMMUNICATIONS. PMID- 17866125 TI - TREATMENT OF ACUTE POST-OPERATIVE THYROID TOXAEMIA. PMID- 17866126 TI - FIBROSARCOMA OF THE THYROID. PMID- 17866128 TI - PRIMARY HYPERNEPHROMA OF THE LIVER: GRAWITZ TUMOR. PMID- 17866127 TI - HOMO-TRANSPLANTATION OF THYROID TISSUE IN CASES OF COMPLETE THYROIDECTOMY FOR CANCER. PMID- 17866129 TI - THE SPREAD OF BACTERIA FROM THE GALL-BLADDER TO THE LIVER. PMID- 17866130 TI - SURGERY OF THE PANCREAS: AT THE ROOSEVELT HOSPITAL FROM 1918 TO 1928. PMID- 17866131 TI - LEFT VAGUS SECTION AND PARTIAL GASTRECTOMY FOR DUODENAL ULCER WITH HYPERACIDITY: PRELIMINARY REPORT. PMID- 17866132 TI - SAFETY FACTORS IN RESECTION OF STOMACH FOR GASTRODUODENAL ULCERS. PMID- 17866133 TI - LATE RESULTS IN PERFORATED GASTRODUODENAL ULCERS. PMID- 17866134 TI - RESECTION OF THE PROXIMAL DUODENUM AND PYLORIC SPHINCTER FOR MULTIPLE DUODENAL ULCERS. PMID- 17866135 TI - HIGH VEIN LIGATION IN THROMBO-ANGIITIS OBLITERANS: A REPORT OF NINE CASES. PMID- 17866136 TI - EVALUATION OF BLOOD CLOTTING FACTORS IN SURGICAL DISEASES: WITH SPECIAL REFERENCE TO THROMBOSIS AND EMBOLISM AND CERTAIN BLEEDING CONDITIONS. PMID- 17866138 TI - THE PART WHICH IODINE HAS PLAYED IN THE TREATMENT OF PATIENTS WITH EXOPHTHALMIC GOITRE. PMID- 17866137 TI - HYPERGLYCEMIA FOLLOWING HEAD INJURIES: AN EXPERIMENTAL CLINICAL STUDY. PMID- 17866139 TI - TREATMENT OF ABDOMINAL INJURIES IN CHILDREN: WITH THE REPORT OF FIFTY-NINE CASES. PMID- 17866141 TI - SUBPHRENIC ABSCESS. PMID- 17866140 TI - A TREATMENT OF PERSISTENT BRONCHIAL FISTULA: AN EXPERIMENTAL AND CLINICAL STUDY. PMID- 17866142 TI - GONORRHOEAL INFECTION OF ABDOMINAL WOUNDS FOLLOWING LAPAROTOMY. PMID- 17866143 TI - LYMPHOSARCOMA OF THE GASTRO-INTESTINAL TRACT: WITH A REPORT OF THIRTEEN CASES. PMID- 17866144 TI - THE POST-OPERATIVE COMPLICATIONS OF CHOLECYSTECTOMY: A STUDY OF 700 CHOLECYSTECTOMIES. PMID- 17866145 TI - CARCINOID TUMORS OF THE APPENDIX. PMID- 17866147 TI - EMULSIFIED CAMPIODOL AS A PYELOGRAPHIC MEDIUM. PMID- 17866146 TI - ROUTINE REMOVAL OF THE APPENDIX IN RIGHT INGUINAL HERNIORRHAPHY: REPORT OF NINETY SIX APPENDECTOMIES IN ONE HUNDRED CONSECUTIVE OPERATIONS FOR HERNIA. PMID- 17866148 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD MARCH 13, 1929. PMID- 17866149 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD MARCH 27, 1929. PMID- 17866150 TI - WREDEN'S METHOD OF RECONSTRUCTING VOLUNTARY ANAL CONTROL. PMID- 17866151 TI - FRACTURE DISLOCATION OF THE CERVICAL SPINE. PMID- 17866152 TI - OBSERVATIONS ON IMPAIRED SHOULDER FUNCTION AND METHODS OF TREATMENT. PMID- 17866153 TI - INJURIES TO THE ABDOMINAL VISCERA: THEIR RELATIVE FREQUENCY AND THEIR MANAGEMENT. PMID- 17866155 TI - REVIEW OF THE OPERATIONS DONE ON THE GALL-BLADDER AND DUCTS. PMID- 17866154 TI - ACUTE PANCREATITIS: AN ANALYSIS OF EIGHTY-EIGHT CASES WITH ESPECIAL REFERENCE TO DIAGNOSIS. PMID- 17866156 TI - SURGICAL CONDITIONS OF THE BILIARY TRACT. PMID- 17866157 TI - MORTALITY OF ENTEROSTOMY IN ACUTE ILEUS: IMPROVEMENT NOT REFERABLE TO THE TIME ELEMENT. PMID- 17866158 TI - ILEUS FOLLOWING RIB FRACTURE. PMID- 17866159 TI - VON RECKLINGHAUSEN'S DISEASE: WITH SARCOMATOUS DEGENERATION OF A DEEP FIBROMA. PMID- 17866160 TI - HEMIRESECTION OF A SOLITARY KIDNEY. PMID- 17866161 TI - RECTAL ANAESTHESIA WITH TRIBROMETHYLALCOHOL. PMID- 17866162 TI - THE INCIDENCE OF HYPOACIDITY IN CHOLELITHIASIS AND CHOLECYSTITIS. PMID- 17866163 TI - SURGERY IN BREAST TUMORS; PROBLEMS CONCERNING DIAGNOSIS AND TREATMENT. PMID- 17866164 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY STATED MEETING HELD APRIL 1, 1929. PMID- 17866165 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY STATED MEETING HELD MAY 7, 1929. PMID- 17866166 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD APRIL 10, 1929. PMID- 17866167 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD APRIL 24, 1929. PMID- 17866168 TI - BRIEF COMMUNICATIONS. PMID- 17866169 TI - ADDRESS OF THE PRESIDENT: A CONSIDERATION OF CERTAIN FEATURES OF PRESENT MEDICAL EDUCATION AND MEDICAL ETHICS. PMID- 17866170 TI - THE SMALL HOSPITAL-MEDICAL SCHOOL IN AMERICAN MEDICAL EDUCATION-IS THERE A PLACE FOR IT? PMID- 17866171 TI - THE CAUSES OF FAILURE IN THE OPERATIVE TREATMENT OF CARCINOMA OF THE OESOPHAGUS. PMID- 17866172 TI - CONGENITAL HYPERTROPHIC PYLORIC STENOSIS AND ITS OPERATIVE TREATMENT. PMID- 17866173 TI - THERAPEUTIC ASPECTS OF GASTRO-INTESTINAL SUBCOMPETENCE. PMID- 17866174 TI - THE SURGERY OF PYLOROSPASM. PMID- 17866175 TI - THE MANAGEMENT OF RECURRENT ULCER FOLLOWING PARTIAL GASTRECTOMY. PMID- 17866176 TI - PROCESS OF UNION AFTER FRACTURE. PMID- 17866177 TI - IS ACCURATE REDUCTION OF A FRACTURE NECESSARY? PMID- 17866179 TI - THE IMMEDIATE TREATMENT OF OPEN FRACTURES: WITH SPECIAL REFERENCE TO FRACTURES OF THE TIBIA AND THE EVALUATION OF PLATING. PMID- 17866178 TI - NON-UNION AFTER FRACTURE. PMID- 17866180 TI - THE TREATMENT OF RECENT FRACTURES OF THE LONG BONES BY OPERATION. PMID- 17866181 TI - DISASTERS FOLLOWING OPERATIVE TREATMENT OF FRACTURES. PMID- 17866182 TI - GAS GANGRENE IN COMPOUND FRACTURES. PMID- 17866183 TI - TUBERCULOSIS OF THE PERITONEUM. PMID- 17866184 TI - CHRONIC, NON-SPECIFIC ENLARGEMENT OF THE MESENTERIC LYMPH NODES, AS RELATED TO SURGERY. PMID- 17866185 TI - THE SURGICAL TREATMENT OF BILE TYPHOID CARRIERS. PMID- 17866187 TI - THE REMOVAL OF WIDE SCARS AND LARGE DISFIGUREMENTS OF THE SKIN BY GRADUAL PARTIAL EXCISION WITH CLOSURE. PMID- 17866186 TI - THE FOWLER POSITION AND ITS RELATION TO DILATATION OF THE STOMACH. PMID- 17866188 TI - TRAUMATIC RUPTURE AS A SEQUENCE TO CONGENITAL HERNIA OF THE DIAPHRAGM, WITH AN EXPERIMENTAL STUDY OF ITS MECHANISM AND THE EFFECTS OF PHRENICOTOMY. PMID- 17866189 TI - RESECTION OF RECTUM FOR CANCER AND CONTINUITY RESTORED. PMID- 17866190 TI - END RESULTS OF RADICAL OPERATIONS FOR CARCINOMA OF THE RECTUM. PMID- 17866191 TI - THE SURGERY OF MEDIASTINAL DERMOIDS: BASED UPON AN EXPERIENCE WITH FOUR CASES AND A REVIEW OF THE LITERATURE. PMID- 17866192 TI - CONGENITAL MEDIASTINAL CYSTS OF GASTROGENIC AND BRONCHOGENIC ORIGIN. PMID- 17866193 TI - PARATHYROIDECTOMY IN OSTEOMALACIA. PMID- 17866194 TI - PAROXYSMAL HYPERTENSION ASSOCIATED WITH TUMOR OF THE SUPRARENAL. PMID- 17866196 TI - CHRONIC FIBROUS OSTEOMYELITIS. PMID- 17866195 TI - END RESULTS IN THYROCARDIACS. PMID- 17866197 TI - RETROCAECAL INTERNAL HERNIA. PMID- 17866198 TI - ACUTE ABDOMINAL PAIN, ASSOCIATED WITH SPINAL CORD SHOCK. PMID- 17866199 TI - SOME UNUSUAL TYPES OF ABDOMINAL HAEMORRHAGE. PMID- 17866200 TI - GLUCOSE TOLERANCE AND HEPATIC DAMAGE. PMID- 17866202 TI - DR. CLARENCE LESLIE STARR 1868-1928. PMID- 17866201 TI - THOMAS W. HUNTINGTON, M.D. 1849-1929. PMID- 17866204 TI - SIR ANTHONY BOWLBY, HONORARY FELLOW. PMID- 17866203 TI - RICHARD WALKER BOLLING, M.D. 1882-1929. PMID- 17866205 TI - PRESIDENTIAL ADDRESS. PMID- 17866206 TI - ACUTE OEDEMA OF THE PANCREAS: A CLINICAL AND EXPERIMENTAL STUDY. PMID- 17866207 TI - DECOMPRESSION OF THE HEART. PMID- 17866208 TI - THE DEVELOPMENT OF SURGERY OF THE STOMACH: WITH SPECIAL REFERENCE TO THE PART PLAYED BY AMERICAN SURGEONS. PMID- 17866209 TI - THE OPERATION FOR UNDESCENDED TESTIS: A FURTHER STUDY AND REPORT. PMID- 17866210 TI - TOTAL CYSTECTOMY AND PARTIAL PROSTATECTOMY FOR INFILTRATING CARCINOMA OF THE NECK OF THE BLADDER: REPORT OF EIGHT OPERATED CASES. PMID- 17866211 TI - CHRONIC CYSTIC MASTITIS OF THE DIFFUSE, NON-ENCAPSULATED, CYSTIC ADENOMATOUS TYPE: SHOTTY BREAST. PMID- 17866212 TI - THE SURGICAL TREATMENT OF DUODENAL ULCER: END-RESULTS OVER A TWENTY-FIVE YEAR PERIOD. PMID- 17866213 TI - THE RELATION OF BIOCHEMISTRY TO CANCER. PMID- 17866215 TI - THE FUNCTION OF THE GALL-BLADDER. PMID- 17866214 TI - HOMOTRANSPLANTATION AND THE SEVERAL BLOOD GROUPS: CONSIDERATIONS ON EPIDERMAL GRAFTS MADE BY THE THIERSCH METHOD. PMID- 17866216 TI - TEMPORARY BILATERAL ABDUCTOR PARALYSIS WITHOUT NERVE INJURY AFTER THYROIDECTOMY. PMID- 17866217 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD MAY 8, 1929. PMID- 17866218 TI - RADIATION IN THE TREATMENT OF RECTAL CANCER. PMID- 17866219 TI - SIGMOIDOVESICAL FISTULAE: WITH SPECIAL REFERENCE TO SIGMOID DIVERTICULITIS. PMID- 17866220 TI - ACUTE PERFORATED ULCERS OF THE STOMACH AND DUODENUM. PMID- 17866221 TI - THE PHYSIOLOGY OF THE LIVER AND ITS RELATION TO SURGERY OF THE BILIARY TRACT. PMID- 17866222 TI - CHRONIC CALCULOUS CHOLECYSTITIS. PMID- 17866223 TI - ACCIDENTAL OR COMPENSABLE HERNIA: REPORT OF THE COMMITTEE OF THE AMERICAN RAILWAY ASSOCIATION. PMID- 17866224 TI - THE TREATMENT OF ELECTRIC BURNS BY IMMEDIATE RESECTION AND SKIN GRAFT. PMID- 17866226 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD OCTOBER 9, 1929. PMID- 17866225 TI - SUBCUTANEOUS STREPTOCOCCUS GANGRENE. PMID- 17866227 TI - BRIEF COMMUNICATIONS. PMID- 17866228 TI - MEMOIR: FRANK EMORY BUNTS, M.D. 1861-1928. PMID- 17866229 TI - THE PROBLEM OF RHINOPLASTY. PMID- 17866230 TI - RESTORATION OF THE SUB-SEPTAL PORTION OF THE NOSE. PMID- 17866231 TI - PARATHYROIDECTOMY FOR ANKYLOSING POLYARTHRITIS. PMID- 17866232 TI - DIRECT AND INDIRECT INJURY TO THE RECURRENT LARYNGEAL NERVES DURING THYROIDECTOMY. PMID- 17866234 TI - RELATIONS OF HISTOLOGICAL STRUCTURE AND CLINICAL GROUPING TO THE PROGNOSIS OF CARCINOMATA OF THE BREAST AND UTERINE CERVIX. PMID- 17866233 TI - IMMEDIATE AND EVENTUAL FEATURES OF HEALING IN AMPUTATED BONES. PMID- 17866235 TI - THE SEMICENTENNIAL ANNIVERSARY OF THE FOUNDING OF THE NEW YORK SURGICAL SOCIETY Held October 30, 1929: INTRODUCTORY REMARKS. PMID- 17866236 TI - URETEROPYELONEPHROSTOMY FOR URINARY OBSTRUCTION AT THE URETERO PELVIC JUNCTION. PMID- 17866237 TI - TUBERCULOSIS OF THE PROSTATE GLAND. PMID- 17866238 TI - TESTICULAR NEOPLASMS: THE RELATION BETWEEN THE PATHOLOGIC HISTOLOGY, CLINICAL COURSE, AND REACTION TO IRRADIATION IN TESTICULAR NEOPLASMS. PMID- 17866239 TI - KAOLIN IN THE TREATMENT OF EXTERNAL GASTRO-INTESTINAL FISTULAS. PMID- 17866240 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD NOVEMBER 13, 1929. PMID- 17866241 TI - EARLY DAYS OF THE NEW YORK SURGICAL SOCIETY. PMID- 17866242 TI - BRIEF COMMUNICATIONS. PMID- 17866243 TI - THE SEMICENTENNIAL ANNIVERSARY OF THE NEW YORK SURGICAL SOCIETY. PMID- 17866244 TI - EVALUATION OF CARDIAC AND CIRCULATORY STIMULANTS FOR SURGICAL PATIENTS. PMID- 17866245 TI - TREATMENT OF PITUITARY TUMORS: THE ROLE OF THE RONTGEN-RAY AND OF SURGERY THEREIN. PMID- 17866246 TI - THE INFLUENCE OF THE NEW YORK SURGICAL SOCIETY ON THE DEVELOPMENT OF SURGERY. PMID- 17866248 TI - SARCOMA OF THE THYROID GLAND. PMID- 17866247 TI - GIANT CELL TUMOR OF THE SPINE. PMID- 17866249 TI - EXTRAPLEURAL THORACOPLASTY DURING THE TREATMENT OF PULMONARY TUBERCULOSIS. PMID- 17866250 TI - CHANGES IN THE INTRAHEPATIC BILE DUCTS FOLLOWING CHOLECYSTECTOMY. PMID- 17866251 TI - OBSERVATIONS ON PEPTIC ULCER: VII. CLINICAL CORROBORATION OF EXPERIMENTAL DATA. PMID- 17866252 TI - TUBERCULOSIS OF THE SIGMOID COLON SIMULATING A PRIMARY MALIGNANT LESION. PMID- 17866253 TI - THE SURGICAL MANAGEMENT OF STONE IN THE URETER. PMID- 17866255 TI - TREATMENT OF ANEURYSMS OF THE THORACIC AORTA AND INNOMINATE ARTERY BY DISTAL ARTERIO-VENOUS ANASTOMOSIS: OBSERVATIONS ON TEN CASES WITH OPERATIONS IN EIGHT CASES. PMID- 17866254 TI - PROBLEMS RELATED TO SURGICAL LESIONS OF THE KIDNEY. PMID- 17866256 TI - SANGUINEOUS DISCHARGE FROM THE NIPPLE AND ITS SIGNIFICANCE IN RELATION TO CANCER OF THE BREAST: A STUDY BASED ON 108 CASES. PMID- 17866257 TI - PHRENIC NERVE SURGERY. PMID- 17866258 TI - OESOPHAGEAL OBSTRUCTION: CAUSES, DIAGNOSIS AND SURGICAL TREATMENT. PMID- 17866259 TI - TESTS OF HEPATIC FUNCTION IN CARCINOMA; THEIR VALUE IN CASES OF NEOPLASM OF THE COLON WITH AND WITHOUT METASTASIS TO THE LIVER. PMID- 17866260 TI - LIPIODOL STUDIES OF POST-OPERATIVE BILIARY FISTULAE. PMID- 17866261 TI - OBSERVATIONS ON SPINAL ANAESTHESIA. PMID- 17866262 TI - SPINAL ANAESTHESIA IN MAJOR SURGERY: BASED ON A STUDY OF 1000 CASES. PMID- 17866263 TI - THE TREATMENT OF GAS GANGRENE WITH NORMAL HORSE SERUM. PMID- 17866264 TI - SYPHILIS AMONG SOUTHERN NEGRO MALES. PMID- 17866266 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 7, 1929: Stated Meeting Held October. PMID- 17866265 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 27, 1929: Stated Meeting Held November. PMID- 17866267 TI - BRIEF COMMUNICATIONS. PMID- 17866268 TI - Francis Wisner Murray M.D. 1873-1929. PMID- 17866269 TI - THE CAUSES OF DEATH AFTER OPERATION: A STUDY BASED ON EIGHT HUNDRED AUTOPSIES. PMID- 17866271 TI - BRONCHIAL INJURY AND REPAIR. PMID- 17866270 TI - POST-OPERATIVE SHOCK AND SHOCK-LIKE CONDITIONS TREATMENT BY INFUSION IN LARGE VOLUME. PMID- 17866272 TI - MORTALITY AND END RESULTS OF OPERATION FOR ABSCESS OF THE LUNG. PMID- 17866273 TI - DIAPHRAGMATIC HERNIA. PMID- 17866274 TI - DIAPHRAGMATIC HERNIA: Phrenic Nerve Stimulation Under Fluoroscope as an Aid in Diagnosis. PMID- 17866275 TI - ACUTE PANCREATITIS. PMID- 17866276 TI - A CLINICAL STUDY OF CALCIFIED NODES IN THE MESENTERY. PMID- 17866277 TI - THE INJECTION TREATMENT OF VARICOSE VEINS. PMID- 17866278 TI - THE CONTINUOUS INTRAVENOUS ADMINISTRATION OF PHYSIOLOGICAL SALT SOLUTION. PMID- 17866279 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY STATED MEETING HELD NOVEMBER 4, 1929. PMID- 17866280 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY STATED MEETING HELD DECEMBER 2, 1929. PMID- 17866281 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD DECEMBER 11, 1929. PMID- 17866282 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD JANUARY 8, 1930. PMID- 17866283 TI - BRIEF COMMUNICATIONS. PMID- 17866284 TI - MEMOIR: FRANCIS JOHN SHEPHERD, M.D., C.M., L.L.D., F.R.C.S. 1851-1929. PMID- 17866285 TI - OBSERVATIONS ON BLOOD GROUPING AND BLOOD TRANSFUSION. PMID- 17866287 TI - EXPERIENCES WITH SODIUM AMYTAL AS A GENERAL ANAESTHETIC. PMID- 17866286 TI - RELATION OF PROTEIN DIET TO THROMBOSIS: THE IMPORTANCE OF BLOOD COAGULABILITY AND DIETARY TREATMENT IN THROMBOSIS AND HAEMORRHAGIC CONDITIONS. PMID- 17866289 TI - MESENTERIC CYSTS: WITH REPORT OF CASE OF CYSTIC LYMPHANGIOMA. PMID- 17866288 TI - AN ANALYSIS OF ONE HUNDRED AND FORTY-EIGHT OPERATIONS FOR GOITER. PMID- 17866290 TI - EFFICIENCY OF THE VARIOUS TYPES OF ANASTOMOSES OF THE HOLLOW VISCERA: CLINICAL AND EXPERIMENTAL DATA. PMID- 17866292 TI - CURLING'S ULCER: DUODENAL ULCER FOLLOWING SUPERFICIAL BURNS. PMID- 17866291 TI - OPERATIVE RESULTS IN PARTIAL AND SUBTOTAL GASTRECTOMY FOR GASTRO-DUODENAL ULCERS. PMID- 17866293 TI - DUODENITIS AND DUODENAL ULCER. PMID- 17866294 TI - PRIMARY SOLITARY DIVERTICULITIS OF CAECUM. PMID- 17866295 TI - THE INTRA-ABDOMINAL POST-OPERATIVE COMPLICATIONS OF APPENDICITIS. PMID- 17866296 TI - PEPTIC ULCER OF MECKEL'S DIVERTICULUM AND ILEUM. PMID- 17866297 TI - MULTIPLE CARCINOMATA OF THE LARGE INTESTINE. PMID- 17866298 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD JANUARY 22, 1930. PMID- 17866299 TI - BRIEF COMMUNICATIONS. PMID- 17866301 TI - CARL A. HAMANN 1868-1930. PMID- 17866300 TI - THEODORE TUFFIER 1857-1929. PMID- 17866302 TI - EFFECT OF HIGH PROTEIN DIET ON THE VELOCITY OF GROWTH OF FIBROBLASTS IN THE HEALING WOUND. PMID- 17866303 TI - THE INCIDENCE OF ALLERGY AND ASTHMA IN A GROUP DEVELOPING POST-OPERATIVE ATELECTASIS. PMID- 17866304 TI - PARTIAL RIB-REMOVAL WITH CLOSED DRAINAGE IN THE TREATMENT OF ACUTE EMPYEMA IN INFANCY AND CHILDHOOD. PMID- 17866305 TI - PHRENIC EXAIRESIS IN THE TREATMENT OF PULMONARY TUBERCULOSIS. PMID- 17866306 TI - TRAUMATIC DIAPHRAGMATIC HERNIA. PMID- 17866307 TI - THE COMPOSITION OF THE BILE FOLLOWING THE RELIEF OF BILIARY OBSTRUCTION: REPORT OF A SERIES OF ILLUSTRATIVE CASES. PMID- 17866308 TI - THE SEDIMENTATION RATE OF BLOOD AS AN INDEX OF THE HAEMORRHAGIC TENDENCY IN OBSTRUCTIVE JAUNDICE. PMID- 17866310 TI - INTUSSUSCEPTION COMPLICATING VISCERAL (HENOCH'S) PURPURA. PMID- 17866309 TI - THE SURGICAL IMPORTANCE OF THE OMENTUM. PMID- 17866311 TI - THE MORTALITY FROM APPENDICITIS. PMID- 17866313 TI - OBSTETRICAL PARALYSIS. PMID- 17866312 TI - SUPPURATIVE RETROPERITONEAL PELVIC LYMPHADENITIS. PMID- 17866315 TI - THE MANAGEMENT OF FRACTURE OF THE FEMUR. PMID- 17866314 TI - OPERATIVE TREATMENT OF COMPRESSION FRACTURES OF THE CALCANEUS. PMID- 17866316 TI - TREATMENT OF FRACTURE OF THE NECK OF THE FEMUR IN THE AGED. PMID- 17866318 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY STATED MEETING HELD JANUARY 7, 1930. PMID- 17866317 TI - EXPERIENCES WITH VENOCLYSIS. PMID- 17866320 TI - BRIEF COMMUNICATIONS. PMID- 17866319 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD FEBRUARY 26, 1930. PMID- 17866321 TI - MEMOIR: DR. JOHN DIKEMAN RUSHMORE 1845-1929. PMID- 17866322 TI - COAGULATION OF BLOOD: 1. THE COMPARATIVE VALUES OF CALCIUM AND GLUCOSE AS AGENTS FOR DECREASING THE CLOTTING TIME. PMID- 17866323 TI - BONE METASTASES IN CANCER OF THE BREAST. PMID- 17866324 TI - OSTEITIS FIBROSA: CASE REPORTS SUGGESTING A TRAUMATIC ORIGIN. PMID- 17866325 TI - THE CURABILITY OF CANCER. PMID- 17866326 TI - SPASMODIC TORTICOLLIS: INTERRUPTION OF THE AFFERENT SYSTEM ALONE IN THE TREATMENT. PMID- 17866327 TI - THE BACTERIOPHAGE IN SURGERY. PMID- 17866328 TI - CLINICAL EXPERIENCE WITH GASTROPHOTOGRAPHY. PMID- 17866329 TI - SIMPLIFIED TREATMENT OF THORACIC EMPYEMA. PMID- 17866330 TI - AMYTAL AS AN ANAESTHETIC IN OPERATIONS FOR GOITRE: THE ORAL ADMINISTRATION OF BARBITURIC ACID COMPOUNDS. PMID- 17866331 TI - TRANSPLANTATION OF THE URETERS: FOR CANCER OF THE BLADDER WITH CYSTECTOMY. PMID- 17866332 TI - TEN YEARS OF THE TUNNEL SKIN GRAFT. PMID- 17866333 TI - END-RESULTS IN BUNION SURGERY. PMID- 17866335 TI - THE OPERATIVE TREATMENT FOR INJURED CARTILAGES OF THE KNEE-JOINT. PMID- 17866334 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY AND THE NEW YORK SURGICAL SOCIETY ANNUAL CONJOINT MEETING HELD FEBRUARY 13, 1930. PMID- 17866337 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 12, 1930: Stated Meeting Held March. PMID- 17866336 TI - ON THE CAUSES OF POST-OPERATIVE DEATHS. PMID- 17866339 TI - BRIEF COMMUNICATIONS. PMID- 17866338 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY 26, 1930: Stated Meeting Held March. PMID- 17866340 TI - RESULTS OF TREATMENT BY AUTOGENOUS GLAND FILTRATE IN HODGKIN'S DISEASE. PMID- 17866342 TI - PLASTIC RESTORATION OF THE OESOPHAGUS. PMID- 17866341 TI - HARE-LIP AND CLEFT PALATE: AN ANALYSIS OF 184 CASES. PMID- 17866343 TI - THYROGLOSSAL CYSTS AND SINUSES. PMID- 17866344 TI - MULTILOCULAR CYST OF THE SPLEEN PRODUCED BY INFARCTS. PMID- 17866345 TI - IMPERFORATE ANUS: A METHOD OF DETERMINING THE SURGICAL APPROACH. PMID- 17866346 TI - PULSATING EXOPHTHALMOS. PMID- 17866347 TI - PRIMARY CLOSURE IN PROSTATECTOMY. PMID- 17866349 TI - OSTEOPERIOSTEAL BONE GRAFTS. PMID- 17866348 TI - HEREDITARY DEFORMING CHONDRODYSPLASIA OR MULTIPLE EXOSTOSES: REPORT OF A FATHER AND TWO DAUGHTERS SHOWING SIMILAR MULTIPLE SYMMETRICAL EXOSTOSES AND FIFTY OTHER CASES COLLECTED FROM THE ENGLISH LITERATURE SINCE 1917. PMID- 17866351 TI - TRAUMATIC LESIONS OF THE BRACHIAL PLEXUS. PMID- 17866350 TI - BIOPSY BY NEEDLE PUNCTURE AND ASPIRATION. PMID- 17866352 TI - THE CAUSE AND ELIMINATION OF REACTIONS AFTER INTRAVENOUS INFUSIONS. PMID- 17866353 TI - HYPERPARATHYROIDISM. PMID- 17866354 TI - THE TREATMENT OF ACUTE EMPYEMA THORACIS: WITH A REPORT OF 153 CONSECUTIVE CASES. PMID- 17866355 TI - A BACTERIOLOGICAL AND CLINICAL STUDY OF GASTRIC ULCER. PMID- 17866356 TI - ACUTE ULCERATIONS OF THE STOMACH IN CHILDREN. PMID- 17866357 TI - ANNULAR PANCREAS INVOLVED IN ACUTE HAEMORRHAGIC PANCREATITIS. PMID- 17866358 TI - SUBACUTE PANCREATITIS OR SO-CALLED ACUTE OEDEMA OF THE PANCREAS. PMID- 17866359 TI - ECTOPIC SPLEEN CAUSING INTESTINAL OBSTRUCTION. PMID- 17866360 TI - INTESTINAL OBSTRUCTION. PMID- 17866361 TI - THE USE OF PERFRINGENS ANTITOXIN IN INTESTINAL OBSTRUCTION: AN EXPERIMENTAL STUDY. PMID- 17866363 TI - PATHOLOGICAL STUDY OF POSTERIOR VESICAL NECK OBSTRUCTION. PMID- 17866362 TI - THE PREVENTION OF PERITONEAL ADHESIONS BY AMNIOTIC FLUID. PMID- 17866364 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 3, 1930: Stated Meeting Held March. PMID- 17866365 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 7, 1930: Stated Meeting Held April. PMID- 17866366 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD APRIL 9, 1930. PMID- 17866368 TI - THE INFLUENCE OF HYPERTHYROIDISM UPON THE SECRETION OF FREE HYDROCHLORIC ACID. PMID- 17866367 TI - Insulin in the Treatment of Non-Diabetic Bed Sores. PMID- 17866370 TI - CHORDOTOMY FOR INTRACTABLE PELVIC PAIN. PMID- 17866369 TI - CARDIAC ARREST. PMID- 17866371 TI - THE MORTALITY AND LATE RESULTS OF SUBTOTAL GASTRECTOMY FOR THE RADICAL CURE OF GASTRIC AND DUODENAL ULCER. PMID- 17866373 TI - THE END RESULTS IN FIVE HUNDRED CASES OF CHOLECYSTECTOMY. PMID- 17866372 TI - DEFORMITIES AND OBSTRUCTIONS OF THE STOMACH AND DUODENUM. PMID- 17866374 TI - INFLAMMATION OF MECKEL'S DIVERTICULUM. PMID- 17866375 TI - THE SURGICAL TREATMENT OF URINARY INCONTINENCE IN WOMEN. PMID- 17866376 TI - THE SURGICAL TREATMENT OF GENITAL ELEPHANTIASIS IN THE MALE. PMID- 17866377 TI - TORSION OF THE SPERMATIC CORD IN INFANCY. PMID- 17866379 TI - NON-EFFECT OF IRRADIATED ERGOSTEROL IN THE TREATMENT OF FRACTURES. PMID- 17866378 TI - A DEPENDABLE METHOD FOR SUTURING STOMACH AND INTESTINES. PMID- 17866380 TI - INTRAARTICULAR ENDOTHELIAL TUMOR ARISING FROM SYNOVIAL MEMBRANE. PMID- 17866381 TI - MULTIPLE MYELOMA AS A SINGLE LESION. PMID- 17866382 TI - MALIGNANT TUMORS AND THEIR METASTASES: A SUMMARY OF THE NECROPSIES ON EIGHT HUNDRED SIXTY-FIVE CASES PERFORMED AT THE BELLEVUE HOSPITAL OF NEW YORK. PMID- 17866383 TI - DESMOID TUMORS. PMID- 17866384 TI - HERNIA OF THE UMBILICAL CORD (EXOMPHALOS). PMID- 17866385 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY, MEETING OF APRIL 23, 1930. PMID- 17866386 TI - BRIEF COMMUNICATIONS. PMID- 17866387 TI - ADDRESS OF THE PRESIDENT: FIFTY YEARS OF THE AMERICAN SURGICAL ASSOCIATION. PMID- 17866388 TI - EXPERIENCES WITH THE TRENDELENBURG OPERATION FOR PULMONARY EMBOLISM. PMID- 17866389 TI - FURTHER EXPERIENCE WITH RESECTION OF THE ANTERIOR HALF OF THE PYLORIC SPHINCTER. PMID- 17866391 TI - THE IMMEDIATE MORTALITY AND LATE RESULTS OF OPERATIONS FOR GASTRIC AND DUODENAL ULCERS. PMID- 17866390 TI - CARCINOMA OF STOMACH WITHOUT RECURRENCE TWENTY-FOUR YEARS AFTER OPERATION. PMID- 17866393 TI - RESULTS OF GASTROENTEROSTOMY FOR ULCER OF THE DUODENUM AND STOMACH. PMID- 17866392 TI - THE IMMEDIATE MORTALITY AND LATE RESULTS OF OPERATIONS FOR PEPTIC ULCER: PERFORMED IN THE PRESBYTERIAN HOSPITAL OF CHICAGO BETWEEN 1915 AND 1930. PMID- 17866394 TI - THE RESULTS OF OPERATIONS FOR EXCISION OF ULCER OF THE DUODENUM. PMID- 17866395 TI - THE ULTIMATE RESULTS AND THE ACTUAL FUNCTIONAL RESULTS AFTER THE DIFFERENT TYPES OF OPERATIONS FOR GASTRIC AND DUODENAL ULCERS, FOR GASTRIC CANCER AND FOR HOUR GLASS STOMACH AFTER AN INTERVAL OF FIVE YEARS OR MORE. PMID- 17866396 TI - A FOLLOW-UP STUDY OF THE RESULTS IN SURGICAL THERAPY FOR GASTRIC AND DUODENAL ULCER. PMID- 17866397 TI - PEPTIC ULCER SURGICAL ASPECTS INCLUDING END-RESULTS. PMID- 17866398 TI - THE IMMEDIATE MORTALITY IN OPERATIONS FOR GASTRIC AND DUODENAL ULCER AND ITS CAUSES. PMID- 17866399 TI - RESULTS OF OPERATIONS FOR CHRONIC GASTRIC AND DUODENAL ULCERATION: A STATISTICAL STUDY OF A THIRTY-YEAR PERIOD. PMID- 17866400 TI - PHILOSOPHIC CONSIDERATIONS OF THE GALL-BLADDER. PMID- 17866401 TI - ACUTE CHOLECYSTITIS. PMID- 17866402 TI - EXTERNAL AND INTERNAL BILIARY FISTULAE FOLLOWING CHOLECYSTECTOMY. PMID- 17866404 TI - RECONSTRUCTION OF THE BILE PASSAGES WITH SPECIAL REFERENCE TO HEPATICO DUODENOSTOMY. PMID- 17866403 TI - BENIGN PAPILLOMA OF THE COMMON BILE-DUCT. PMID- 17866405 TI - NEUROFIBROMA ARISING ON THE PERICARDIAL PLEURA. PMID- 17866407 TI - CANCER OF THE BUCCAL MUCOSA: THE RESULTS OF TREATMENT BY OPERATION AND RADIATION. PMID- 17866406 TI - OSTEOCHONDROMATOSIS. PMID- 17866408 TI - FURTHER OBSERVATION UPON THE COMPENSATORY USE OF LIVE TENDON STRIPS FOR FACIAL PARALYSIS. PMID- 17866409 TI - ENTEROANASTOMOSIS IN INTESTINAL OBSTRUCTION. PMID- 17866411 TI - SPLANCHNIC ANAESTHESIA IN THE TREATMENT OF PARALYTIC ILENS. PMID- 17866410 TI - SECTION OF THE SYMPATHETIC NERVES OF THE DISTAL PART OF THE COLON AND THE RECTUM IN THE TREATMENT OF HIRSCHSPRUNG'S DISEASE AND CERTAIN TYPES OF CONSTIPATION. PMID- 17866413 TI - DIVERTICULA OF THE SIGMOID. PMID- 17866412 TI - ILEOCAECAL OBSTRUCTION ASSOCIATED WITH APPENDICITIS. PMID- 17866414 TI - END-RESULTS OF INGUINAL HERNIA OPERATIONS. PMID- 17866415 TI - SLIDING HERNIAS OF THE ASCENDING COLON AND CAECUM, THE DESCENDING COLON AND SIGMOID, AND OF THE BLADDER. PMID- 17866416 TI - UROSELECTAN INTRAVENOUS UROGRAPHY. PMID- 17866417 TI - COCCUS INFECTIONS OF THE KIDNEY: THEIR FREQUENCY AND THEIR RELATION TO THE UPPER RESPIRATORY TRACT. PMID- 17866418 TI - VESICOVAGINAL FISTULA. PMID- 17866419 TI - PROGRESSIVE GANGRENOUS, PAINFUL ULCERATION OF THE ABDOMINAL SKIN AND SUBCUTANEOUS TISSUES FOLLOWING OPERATION. PMID- 17866420 TI - STUDY IN POST-OPERATIVE BLOOD CHEMISTRY. PMID- 17866422 TI - THE TREATMENT OF FRACTURES BY OPEN OPERATION AND DIRECT FIXATION: A CRITICAL SURVEY OF AN EXPERIENCE OF TWENTY YEARS, AND MORE PARTICULARLY OF TWO CONSECUTIVE FIVE-YEAR PERIODS. PMID- 17866421 TI - OBSERVATIONS ON POST-OPERATIVE PULMONARY ATELECTASIS: CONSIDERATION OF SOME FACTORS IN ITS ETIOLOGY, PREVENTION AND TREATMENT. PMID- 17866423 TI - FRACTURES OF THE NECK OF THE FEMUR WITH SPECIAL REFERENCE TO THE TREATMENT OF INTRACAPSULAR FRACTURE. PMID- 17866424 TI - PYLORIC OCCLUSION FROM SULPHURIC ACID. PMID- 17866425 TI - ALKALOSIS DUE TO PYLORIC STENOSIS SIMULATING NEPHRITIC URAEMIA. PMID- 17866426 TI - THE SERUM TREATMENT OF BACTERAEMIA DUE TO HAEMOLYTIC STREPTOCOCCUS. PMID- 17866427 TI - STUDIES ON THE ACTIVITY OF THE LUMBAR SYMPATHETIC NERVOUS SYSTEM. PMID- 17866428 TI - RECENT ADVANCES IN THE TREATMENT OF CIRCULATORY DISTURBANCES OF THE EXTREMITIES: RESULTS OBTAINED IN THE PERIPHERAL CIRCULATORY CLINIC OF THE MASSACHUSETTS GENERAL HOSPITAL. PMID- 17866429 TI - THE RONTGEN DIAGNOSIS OF ILEUS. PMID- 17866430 TI - FIBRO-SARCOMA OF THE MEDIASTINUM. PMID- 17866431 TI - POST-OPERATIVE PAROTIDITIS: TREATMENT WITHOUT AND WITH RADIUM. PMID- 17866432 TI - POST-OPERATIVE CORONARY OCCLUSION. PMID- 17866433 TI - LYMPH EXUDATE AND FIBROUS TISSUE. PMID- 17866434 TI - METASTASIS OF THYROID TISSUE TO ABDOMINAL ORGANS: WITH SPECIAL CASE REPORT OF A STRUMA OVARII METASTASIZING TO THE OMENTUM. PMID- 17866435 TI - TUMORS OF THE WALL OF THE THORAX. PMID- 17866437 TI - RETROPERITONEAL FIBROMYXOMA. PMID- 17866436 TI - SARCOMA OF THE BREAST. PMID- 17866438 TI - TETANUS IN NEW ORLEANS: AN ANALYSIS OF 813 CASES. PMID- 17866439 TI - OBSERVATIONS ON THE TREATMENT OF OSTEOMYELITIS BY THE "ORR" METHOD. PMID- 17866440 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 5, 1930: Stated Meeting Held May. PMID- 17866441 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY 6, 1930: Stated Meeting Held October. PMID- 17866442 TI - BRIEF COMMUNICATIONS. PMID- 17866443 TI - Henry Beeckman Delatour 1866-1930. PMID- 17866444 TI - Albert Vander Veer 1841-1930. PMID- 17866445 TI - TUMORS OF PERIPHERAL NERVES. PMID- 17866446 TI - PENETRATING TO THE GASSERIAN GANGLION. PMID- 17866447 TI - CALCIUM CHANGES IN THE BRAIN IN ETHER ANAESTHESIA. PMID- 17866449 TI - EPIDERMOID CARCINOMA IN SEBACEOUS CYSTS. PMID- 17866448 TI - VALUE OF CORDOTOMY FOR THE RELIEF OF PAIN. PMID- 17866450 TI - THE PRESENT STATUS OF THE CANCER PROBLEM. PMID- 17866451 TI - CANCER SERVICE IN MASSACHUSETTS. PMID- 17866452 TI - RELATION OF THE TECHNICIAN TO THE PATHOLOGIST. PMID- 17866454 TI - UNDIFFERENTIATED ROUND-CELL SARCOMAS. PMID- 17866453 TI - A PLEA FOR THE ENCOURAGEMENT OF EPIDEMIOLOGICAL CANCER RESEARCH. PMID- 17866455 TI - INTRACRANIAL CARCINOMATOUS METASTASES: WITH NOTE ON RELATION OF CARCINOMA AND TUBERCLE. PMID- 17866456 TI - AN ANALYSIS OF THE LYMPHADENOPATHY QUESTION WITH SPECIAL REFERENCE TO HODGKIN'S DISEASE AND TUBERCULOSIS. PMID- 17866457 TI - THE GENETIC NEOPLASTIC RELATIONSHIPS OF HODGKIN'S DISEASE, ALEUKAEMIC AND LEUKAEMIC LYMPHOBLASTOMA, AND MYCOSIS FUNGOIDES. PMID- 17866458 TI - SUSCEPTIBILITY TO CANCER. PMID- 17866460 TI - THERAPY OF SPONTANEOUS MOUSE CANCER: FAILURE OF TUBERCULIN, KARKINOLYSIN, AND SOME INORGANIC COMPOUNDS THEREIN. PMID- 17866459 TI - STUDIES IN HODGKIN'S DISEASE. PMID- 17866461 TI - SUSCEPTIBILITY AND RESISTANCE TO TAR CANCER: AN EXPERIMENTAL STUDY. PMID- 17866463 TI - RESISTANCE AND SUSCEPTIBILITY TO CANCER. PMID- 17866462 TI - EXPERIMENTAL AND CLINICAL STUDIES ON THE TREATMENT OF CANCER BY DICHLORETHYLSULPHIDE (MUSTARD GAS. PMID- 17866464 TI - ANIMAL TUMORS AS THERAPEUTIC REAGENTS. PMID- 17866466 TI - ELEPHANTIASIS NERVORUM. PMID- 17866465 TI - MECHANISMUS DER METHYLENBLAUATMUNG. PMID- 17866467 TI - GIANT NEURO-NAEVUS OF THE HAIRY SCALP. PMID- 17866468 TI - TRANSILLUMINATION OF THE BREAST. PMID- 17866469 TI - BORDER-LINE BREAST TUMORS. PMID- 17866470 TI - GIANT INTRACANALICULAR MYXOMA OF THE BREAST: THE SO-CALLED CYSTOSARCOMA PHYLLODES MAMMAE OF JOHANNES MULLER. PMID- 17866471 TI - THE RESULTS OF TREATMENT OF CANCER OF THE BREAST: BASED ON A STUDY OF 489 CASES 1914-1925. PMID- 17866472 TI - METASTASES TO THE SKELETON, BRAIN AND SPINAL CORD FROM CANCER OF THE BREAST AND THE EFFECT OF RADIOTHERAPY. PMID- 17866473 TI - PAPILLOMA OF THE DUODENUM. PMID- 17866474 TI - NATURAL LAW IN PATHOLOGICAL GROWTH. PMID- 17866475 TI - HEREDITY AND CANCER. PMID- 17866476 TI - CARCINOMA PERIGASTRODUODENALE. PMID- 17866477 TI - THE PREVENTION OF CARCINOMA OF THE GALL-BLADDER. PMID- 17866478 TI - ELECTROSURGERY IN GYNAECOLOGY. PMID- 17866479 TI - CARCINOMA OF THE PROSTATE. PMID- 17866480 TI - SOME COMMONER DIFFICULTIES IN DIAGNOSIS AND TREATMENT OF CARCINOMA OF THE RECTUM AND COLON. PMID- 17866481 TI - THE PATHOLOGY ASSOCIATED WITH RUPTURE OF THE SUPRASPINATUS TENDON. PMID- 17866482 TI - IS CANCER A SYSTEMIC DISEASE? PMID- 17866483 TI - L'EPITHELIOMA EPIDERMOIDE DU COL DE L'UTERUS A KERATINISATION PERILOBULAIRE. PMID- 17866484 TI - THE EXPERIMENTAL USE OF A LARGE QUANTITY OF RADIUM IN TREATMENT. PMID- 17866485 TI - INTERSTITIAL RADIATION IN METASTATIC CERVICAL NODES OF EPIDERMOID CARCINOMA. PMID- 17866486 TI - EFFECT OF IRRADIATION UPON A MALIGNANT THYMIC TUMOR. PMID- 17866487 TI - RESULTS IN THE RONTGEN-RAY THERAPY OF GIANT-CELL TUMORS. PMID- 17866488 TI - THE INTERRELATION BETWEEN HEREDITARY PREDISPOSITON AND EXTERNAL FACTORS IN THE CAUSATION OF CANCER: I. NEOPLASMS IN MICE AT THE SITE OF GROSS TRAUMAS STUDIES IN THE INCIDENCE AND INHERITABILITY OF SPONTANEOUS TUMORS IN MICE. 30TH REPORT. PMID- 17866489 TI - RONTGEN THERAPY IN CARCINOMA OF THE BREAST: A STATISTICAL STUDY OF 977 PRIVATE CASES. PMID- 17866490 TI - RESULTS OBTAINED WITH CARCINOMA UTERI TREATED BY RONTGEN-RAYS FROM 1915-1925. PMID- 17866491 TI - THE TREATMENT OF CANCER OF THE BODY OF THE UTERUS BY RADIATION. PMID- 17866492 TI - THE COMBINED RADIUM AND RONTGEN TREATMENT OF CANCER OF THE CERVIX UTERI. PMID- 17866493 TI - TREATMENT OF CARCINOMA OF THE CERVIX UTERI. PMID- 17866494 TI - LES METASTASES DES EPITHELIOMAS DU COL UTERIN LOCALEMENT GUERIS PAR RADIOTHERAPIE. PMID- 17866496 TI - FAR-REACHING EFFECTS OF GAMMA RAYS AND SHORT X-RAYS UPON THE HUMAN HEART: ELECTROCARDIOGRAPHIC RESULTS OF CANCER TREATMENTS GIVEN WITHOUT DIRECT IRRADIATION OF THE HEART. PMID- 17866495 TI - HOW FAR CAN RADIUM REPLACE RADICAL SURGERY FOR CANCER OF THE RECTUM. PMID- 17866497 TI - CANCER AND SMOKING HABITS. PMID- 17866499 TI - ERZEUGUNG VON BOSARTIGEN TUMOREN DURCH EINSPRITZEN VON MILZBREI UND BLUT VON TUMORTRAGENDEN RATTEN UND MAUSEN. PMID- 17866498 TI - THE ROLE OF LYMPH STASIS IN THE GENESIS OF CANCER: THE EVIDENCE OF LYMPHANGITIS IN PAPILLOMATA. PMID- 17866500 TI - MULTIPLE MYELOMA. PMID- 17866502 TI - TREATMENT OF MALIGNANCY. PMID- 17866501 TI - LA METAPLASIE EPITHELIALE ET SES RAPPORTS AVEC LES TUMEURS. PMID- 17866504 TI - Traumatic Pectus Excavatum. PMID- 17866503 TI - Concealed Cancer of the Tongue. PMID- 17866505 TI - Actinomycosis of the Kidney. PMID- 17866507 TI - Indications and Technic of Combined Ureteronephrectomy. PMID- 17866506 TI - Enucleable Multilocular Abscess (Carbuncle) of the Kidney. PMID- 17866508 TI - Extravasation from the Ureter. PMID- 17866509 TI - Fractures at the Condyles of the Femur. PMID- 17866510 TI - Fracture of the Shaft of Both Bones of the Leg: An Analysis of 107 Cases. PMID- 17866511 TI - The Comparative Value of Metaphen in Alcohol-Acetone-Aqueous Solutions in the Pre Operative Disinfection of the Skin. PMID- 17866513 TI - Transactions of the New York Surgical Society-Stated Meetings Oct. 8, 1930. PMID- 17866512 TI - Transactions of the New York Surgical Society-Stated Meetings May 14, 1930. PMID- 17866514 TI - Transactions of the New York Surgical Society-Stated Meetings Oct. 22, 1930. PMID- 17866515 TI - Brief Communications. PMID- 17866516 TI - Electrocauterization in the Treatment of Human Bites. PMID- 17866518 TI - Derangements of the Semilunar Cartilages: Based on a Study of 388 Operative Cases. PMID- 17866517 TI - Circulatory Diseases of the Lower Extremities: With Special References to Tests of Capillary Circulation. PMID- 17866519 TI - Benign Tumors of the Tendon Sheaths of Unusual Size. PMID- 17866520 TI - Varicose Veins: Indications and Contraindications to Injections. PMID- 17866521 TI - Solution of Dextrose and Sodium Chloride for Obliterating Varicose Veins. PMID- 17866522 TI - The Relation of Calcium to the Haemorrhagic Tendency in Obstructive Jaundice. PMID- 17866523 TI - The Use of Exploring Needles and Shadow-casting Media in the Diagnosis of Hepatic and Perihepatic Abscess. PMID- 17866524 TI - An Investigation of the Functions and Symptoms of Surgically Drained Gall Bladder. PMID- 17866526 TI - Cholecystectomy Without Drainage. PMID- 17866525 TI - Gall-Bladder Function: With Special Reference to Cholecystogastrostomy and the Absence of Ascending Cholangitis. PMID- 17866527 TI - Splenectomy for Haemorrhagic Purpura of Children. PMID- 17866529 TI - Torsion of the Great Omentum. PMID- 17866528 TI - End-Results in Radical Operations for Carcinoma of the Periampullar Region of the Duodenum. PMID- 17866530 TI - Carbuncle of Kidney. PMID- 17866531 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meetings Nov. 3. PMID- 17866532 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meetings Dec. 1. PMID- 17866533 TI - Brief Communications. PMID- 17866534 TI - Tumors of the Carotid Body: Report of Twelve Cases Including One of Bilateral Tumor. PMID- 17866535 TI - Surgery of the Phrenic Nerve in Treatment of Intractable Hiccup. PMID- 17866536 TI - Trendelenburg's Operation for Pulmonary Embolism: Report of a Recent Additional Case. PMID- 17866537 TI - Ligation of the Abdominal Aorta for Aneurism of the Common Iliac Artery. PMID- 17866538 TI - The Relation of the Welch Bacillus to Appendicitis and its Complications. PMID- 17866539 TI - Post-Operative Parotitis. PMID- 17866540 TI - Bleeding Gastric and Duodenal Ulcers: Report of 52 Cases. PMID- 17866542 TI - The Surgical Treatment of Some Congenital Abnormalities of the Genito-Urinary Tract. PMID- 17866541 TI - Sacral Chordoma. PMID- 17866543 TI - Solitary Cysts of the Kidney. PMID- 17866544 TI - Ectopic (Pelvic) Kidney. PMID- 17866545 TI - Benign Tumors of the Bladder. PMID- 17866546 TI - Litholapaxy-Method of Preference for the Removal of Vesical Calculi. PMID- 17866548 TI - Acquired Megacolon. PMID- 17866547 TI - Analysis of Seven Hundred Consecutive Appendectomies. PMID- 17866550 TI - The Surgical Aspects of Ascariasis. PMID- 17866549 TI - Is Toxaemia the Cause of Death in Uncomplicated Intestinal Obstruction? PMID- 17866551 TI - Spinal Anaesthesia: An Analysis of 497 Cases. PMID- 17866552 TI - Transactions of the New York Surgical Society-Stated Meetings Nov. 12. PMID- 17866553 TI - Transactions of the New York Surgical Society-Stated Meetings Nov. 26. PMID- 17866555 TI - Fractures of the Scapula. PMID- 17866554 TI - Brief Communications. PMID- 17866556 TI - Calcification in Callus Formation and Fracture Repair. PMID- 17866557 TI - Surgical Management of Cranial Injuries. PMID- 17866558 TI - Apathetic Thyroidism. PMID- 17866560 TI - Results of Thyroidectomy: Analysis of One Hundred Cases. PMID- 17866559 TI - Therapeutic Failures after Operation for Hyperthyroidism. PMID- 17866561 TI - Bilateral Empyema of the Pleural Cavities. PMID- 17866562 TI - Subcutaneous Rupture of the Spleen: Two Cases with Blood Counts Following Splenectomy. PMID- 17866563 TI - Intra-Abdominal Apoplexy. PMID- 17866564 TI - Subphrenic Abscess. PMID- 17866565 TI - The Management of Patients with Gastric and Duodenal Ulcers. PMID- 17866566 TI - Duodeno-jejunostomy as a Substitute for Gastro-enterostomy in Certain cases of Duodenal and Gastric Ulcer and Apparent Obstruction of the Stomach. PMID- 17866567 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting, Jan. 5, 1931. PMID- 17866568 TI - Transactions of the New York Surgical Society-Stated Meeting, Dec. 10, 1930. PMID- 17866569 TI - Brief Communications. PMID- 17866570 TI - Delayed and Non-Union in Fractures in the Adult. PMID- 17866571 TI - Fractures with Special Reference to the Hip, Ankle and Elbow. PMID- 17866573 TI - An Ambulatory Treatment of Malleolar Fractures. PMID- 17866572 TI - Malunion of Fractures of the Femur. PMID- 17866574 TI - The Surgical Treatment of Blepharospasm. PMID- 17866576 TI - Thyroidectomy Performed with the Radio-Knife: Conclusions Based on 160 Operations. PMID- 17866575 TI - Treatment of Pulmonary Abscess by Bronchoscopy. PMID- 17866577 TI - Obstructive Jaundice: Its Surgical Aspects. PMID- 17866578 TI - Intermittent Jaundice due to Neuroma of Cystic and Common Bile Ducts. PMID- 17866579 TI - Asymptomatic Common-Duct Stones. PMID- 17866581 TI - Surgical Aspects of Gall-bladder Disease. PMID- 17866580 TI - The Value of Early Operation for Acute Cholecystitis. PMID- 17866582 TI - Reconstruction of the Common Bile Duct by end-to-end Anastomosis. PMID- 17866583 TI - Partial and Subtotal Gastric Exclusion. PMID- 17866584 TI - Duodeno-Cutaneous Fistulae. PMID- 17866585 TI - Intussusception in an Adult: Associated with Adenoma of Ileum. PMID- 17866586 TI - Jejunal Alimentation: An Experimental Study in Dogs. PMID- 17866587 TI - Intravenous Urography. PMID- 17866588 TI - Primary Carcinoma of the Oviduct. PMID- 17866589 TI - Carcinoma of the Cervical Stump following Subtotal Hysterectomy. PMID- 17866591 TI - Therapeutic and Physical Properties of Ultraviolet irradiated Petrolatum. PMID- 17866590 TI - The Treatment of Gas Gangrene. PMID- 17866592 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting, Feb. 2, 1931. PMID- 17866593 TI - Transactions of the New York Surgical Society-Stated Meeting, Jan 14, 1931. PMID- 17866594 TI - Transactions of the New York Surgical Society-Stated Meeting, Jan 28, 1931. PMID- 17866595 TI - Brief Communications. PMID- 17866596 TI - Adamantinoma of the Lower Jaw. PMID- 17866598 TI - Transactions of the New York Surgical Society and the Philadelphia Academy of Surgery-Joint Meeting, Feb. 11, 1931. PMID- 17866597 TI - Diffuse Endothelioma of Bone: Ewing's Sarcoma. PMID- 17866599 TI - Brief Communications. PMID- 17866600 TI - Haemorrhage Into and Infection of Large Tumors (Pachydermatoceles) of Von Recklinghausen's Disease. PMID- 17866601 TI - Acute Empyaema Thoracis: A Statistical Study with a Comparison of the White and Colored Races. PMID- 17866603 TI - The Function of the Liver in Relation to Surgical Procedures. PMID- 17866602 TI - The Treatment of Lung Abscess and Empyaema by Packing. PMID- 17866604 TI - Tumors of the Extrahepatic Bile-ducts. PMID- 17866606 TI - Haematologic Studies as a Basis for Determining the Risk of Post-operative Haemorrhage in Jaundiced Patients. PMID- 17866605 TI - Primary Staphylococcus Infections of the Nose, Lips and Face. PMID- 17866607 TI - Mesenteric Vascular Occlusion. PMID- 17866608 TI - Orchiopexy for Undescended Testicle. PMID- 17866609 TI - Diabetes in Relation to Surgery. PMID- 17866610 TI - Mortality in Goitre Operations: An Analysis of a Series of 1,755 Operations During the Ten-Year Period, 1920-1929 Inc. PMID- 17866611 TI - Historic Phases of Appendicitis. PMID- 17866612 TI - The Changing Picture of Appendicitis in Adults: A Review of 1,000 Cases. PMID- 17866613 TI - Appendicitis Chronic. PMID- 17866614 TI - Traumatic Industrial Cancer. PMID- 17866615 TI - Foreign Bodies in the Stomach and Intestines. PMID- 17866616 TI - Von Haberer's Technic for Radical Stomach Resection following Previous Gastroenterostomy. PMID- 17866617 TI - Late Results of Simple Suture in Acute Perforation of Duodenal Ulcer. PMID- 17866618 TI - Perforated Peptic Ulcer of Meckel's Diverticulum. PMID- 17866620 TI - Deep Lipomas of the Hand. PMID- 17866619 TI - The Similarity in Effect of Experimental High Intestinal Obstruction and High Complete Intestinal Fistula. PMID- 17866622 TI - Transactions of the New York Surgical Society-Stated Meeting Feb. 25, 1931. PMID- 17866621 TI - Foot Infections of Peridigital Origin: Routes of Spread and Methods of Treatment. PMID- 17866624 TI - Brief Communications. PMID- 17866623 TI - Transactions of the New York Surgical Society-Stated Meeting Mar. 11, 1931. PMID- 17866625 TI - The Differentiation of Organic and Spastic Vascular Occlusions. PMID- 17866626 TI - Compression of the Lumbosacral Roots of the Spinal Cord by Thickened Ligamenta Flava. PMID- 17866627 TI - Fractures of the Upper Jaw and Malar Bone. PMID- 17866628 TI - Gastro-Intestinal Obstruction-Functional and Organic. PMID- 17866629 TI - Application and Interpretation of Blood Sugar Time Curves in the Diagnosis and Treatment of Surgical Infections of the Gall-bladder and Biliary Passages. PMID- 17866630 TI - Rapid High-Temperature Deaths Following Biliary-Tract Surgery. PMID- 17866631 TI - Cholecystostomy: With Special Reference to Post-Operative Morbidity and Function. PMID- 17866632 TI - Cancer of the Uterus: With General Remarks on the Pathologic Aspects of Cancer of the Uterus. PMID- 17866634 TI - Internal Derangements of the Knee. PMID- 17866633 TI - Aspiration of Joint Effusions. PMID- 17866635 TI - The Behavior of Alcohol-preserved Fascia Lata of the Ox, Autogenous Fascia and Chromicized Kangaroo Tendon in Dog and in Man. PMID- 17866636 TI - Improved Armamentarium for Fracture Reduction and Retention. PMID- 17866637 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting March 2, 1931. PMID- 17866639 TI - Transactions of the New York Surgical Society-Stated Meeting March 25, 1931. PMID- 17866638 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting April 6, 1931. PMID- 17866641 TI - Brief Communications. PMID- 17866640 TI - Transactions of the New York Surgical Society-Stated Meeting April 8, 1931. PMID- 17866642 TI - ADDRESS OF THE PRESIDENT: A STUDY IN RECORDS. PMID- 17866643 TI - RECONSTRUCTIVE OPERATIONS FOR JEJUNAL ULCER. PMID- 17866644 TI - CALCIUM CARBONATE GALL-STONES AND CALCIFICATION OF THE GALL-BLADDER FOLLOWING CYSTIC-DUCT OBSTRUCTION. PMID- 17866645 TI - GASTRIC ULCERS DEPENDENT UPON DIAPHRAGMATIC HERNIA. PMID- 17866646 TI - TUMORS OF THE DIAPHRAGM. PMID- 17866647 TI - SYMPTOMS AND PHYSICAL SIGNS INDICATING HERNIA OF THE DIAPHRAGM WITH REPORT OF TWELVE CASES TREATED BY OPERATION. PMID- 17866648 TI - THE PRESENT STATUS OF THE TREATMENT OF TUBERCULOSIS OF THE CERVICAL LYMPH-NODES. PMID- 17866649 TI - PARACELSUS. PMID- 17866650 TI - A CASE OF THYROIDITIS SIMPLEX (REIDEL'S TUMOR). PMID- 17866651 TI - THYROID SURGERY AT THE PORTLAND CLINIC. PMID- 17866652 TI - THE END-RESULTS OF THYROIDECTOMY. PMID- 17866653 TI - PROGRESSIVE EXOPHTHALMOS FOLLOWING THYROIDECTOMY; ITS PATHOLOGY AND TREATMENT. PMID- 17866654 TI - ELECTRO-SURGERY WITH SPECIAL REFERENCE TO GOITRE AND MALIGNANCY. PMID- 17866655 TI - PARATHYROIDISM AND PARATHYROIDECTOMY. PMID- 17866656 TI - RESECTION OF THE CAECUM. PMID- 17866657 TI - SURGICAL TREATMENT OF TUBERCULOMA OF THE CAECUM. PMID- 17866658 TI - DIVERTICULITIS OF THE COLON: A REPORT OF 36 CASES FROM THE NEW YORK HOSPITAL. PMID- 17866659 TI - BACTERIOPHAGE IN SURGERY OF THE COLON AND RECTUM. PMID- 17866661 TI - TREATMENT OF MEGALOCOLON BY SYMPATHECTOMY. PMID- 17866660 TI - DIVERTICULITIS AND SIGMOIDITIS. PMID- 17866662 TI - TOTAL COLECTOMY; ITS INDICATION AND TECHNIC. PMID- 17866664 TI - INTESTINAL OBSTRUCTION FROM CARCINOMA OF COLON. PMID- 17866663 TI - THE CHOICE OF OPERATION IN CARCINOMA OF THE COLON. PMID- 17866665 TI - SURGERY OF THE LARGE INTESTINE. PMID- 17866666 TI - THE ACTION OF SODIUM CHLORIDE UPON THE SMALL INTESTINE. PMID- 17866667 TI - SPINAL ANAESTHESIA. PMID- 17866669 TI - RESULTS OF SPLENECTOMY IN SPLENIC ANAEMIA, HAEMOLYTIC JAUNDICE, AND HAEMORRHAGIC PURPURA. PMID- 17866668 TI - CLINICAL EXPERIENCES WITH GWATHMEY'S COLONIC OIL-ETHER ANAESTHESIA. PMID- 17866670 TI - ABSCESS OF THE LIVER. PMID- 17866671 TI - THE SELECTIVE SURGICAL TREATMENT OF DIAPHRAGMATIC HERNIA. PMID- 17866672 TI - LATE RESULTS OF SURGICAL AND MEDICAL TREATMENT OF CHRONIC CHOLECYSTITIS. PMID- 17866674 TI - SEVENTIETH BIRTHDAY ANNIVERSARY OF WILLIAM J. MAYO. PMID- 17866673 TI - TUBERCULOSIS OF THE OESOPHAGUS: REPORT OF A CASE WITHOUT ACTIVE TUBERCULOSIS ELSEWHERE. PMID- 17866675 TI - IDIOPATHIC DILATATION OF THE OESOPHAGUS. PMID- 17866677 TI - HAEMANGIOMA OF SIGMOID AND COLON. PMID- 17866676 TI - THE PYLORIC SPHINCTER AND DUODENAL ULCER. PMID- 17866678 TI - SOME ANGIOSPASTIC SYNDROMES IN THE EXTREMITIES. PMID- 17866679 TI - THE DIAGNOSIS AND PRINCIPLES OF TREATMENT OF CARCINOMA OF THE COLON AND RECTUM. PMID- 17866680 TI - THE RELAXATION OF SCAR CONTRACTURES BY MEANS OF THE Z-, OR REVERSED Z-TYPE INCISION: STRESSING THE USE OF SCAR INFILTRATED TISSUES. PMID- 17866681 TI - AVERTIN ANAESTHESIA: FROM THE ANAESTHETIST'S STANDPOINT: A RESUME OF EIGHTEEN MONTHS' EXPERIENCE. PMID- 17866682 TI - AVERTIN ANAESTHESIA: FROM THE SURGICAL STANDPOINT: A RESUME OF EIGHTEEN MONTHS' EXPERIENCE. PMID- 17866683 TI - THE RESULTS OF AVERTIN BASIS ANAESTHESIAS, WITH ETHER, NITROUS OXYGEN AND ETHYLENE-BASED ON CLINICAL AND METABOLIC STUDIES-REPORT OF 700 CASES. PMID- 17866684 TI - A STUDY OF SPINAL ANALGESIA BASED UPON 357 PERSONAL CASES. PMID- 17866686 TI - SPINAL ANAESTHESIA ON A GENERAL SURGICAL SERVICE. PMID- 17866685 TI - SPINAL ANAESTHESIA: REPORT ON A SPINAL ANAESTHESIA QUESTIONNAIRE AND A SERIES OF SPINAL ANAESTHESIAS. PMID- 17866687 TI - SPINAL ANAESTHESIA WITH NUPERCAINE AND PROCAINE: A COMPARATIVE STUDY. PMID- 17866689 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY: STATED MEETING HELD MAY 4, 1931. PMID- 17866688 TI - SUTURING THE BONES OF THE FOREARM. PMID- 17866690 TI - BRIEF COMMUNICATIONS. PMID- 17866691 TI - BRILLIANT GREEN: A CLINICAL STUDY OF ITS VALUE AS A LOCAL ANTISEPTIC. PMID- 17866692 TI - SOME INDICATIONS FOR SECTION OF THE POSTERIOR ROOT OF THE TRIGEMINAL NERVE THROUGH THE POSTERIOR FOSSA. PMID- 17866694 TI - THE EVALUATION OF RESULTS IN 324 GASTRIC AND DUODENAL ULCERS. PMID- 17866693 TI - PENETRATING WOUNDS OF THE ABDOMEN. PMID- 17866696 TI - DIVERTICULUM OF THE MALE URINARY BLADDER. PMID- 17866695 TI - VOLVULUS OF A SIGMOID MEGACOLON. PMID- 17866697 TI - EXTIRPATION OF PREGNANT UTERUS AT FULL TERM. PMID- 17866699 TI - DUODENAL HERNIA. PMID- 17866698 TI - INTERPARIETAL HERNIAS. PMID- 17866700 TI - THE RONTGENOGRAPHIC VISUALIZATION OF THE ARTERIES OF THE EXTREMITIES IN PERIPHERAL VASCULAR DISEASE. PMID- 17866702 TI - TRANSACTIONS OF THE NEW YORK SURGICAL SOCIETY STATED MEETING HELD MAY 13, 1931. PMID- 17866701 TI - GANGRENE OF THE FINGER FOLLOWING DIGITAL NERVE BLOCK ANAESTHESIA. PMID- 17866703 TI - BRIEF COMMUNICATIONS. PMID- 17866705 TI - SPINA BIFIDA: A CLINICAL STUDY WITH A REPORT OF TWELVE PERSONAL CASES. PMID- 17866704 TI - BACTERIAL SYNERGISM IN DISEASE PROCESSES: WITH A CONFIRMATION OF THE SYNERGISTIC BACTERIAL ETIOLOGY OF A CERTAIN TYPE OF PROGRESSIVE GANGRENE OF THE ABDOMINAL WALL. PMID- 17866706 TI - Congenital Cysts and Fistulae of the Neck. PMID- 17866707 TI - Antivirus Treatment of Malignant OEdema Infections. PMID- 17866708 TI - Closing the Bronchial Stump in Pulmonary Surgery. PMID- 17866709 TI - Traumatic Rupture of Congenital Hydronephrotic Kidney. PMID- 17866711 TI - Transactions of the New York Surgical Society-Stated Meeting April 22, 1931. PMID- 17866710 TI - Cyst of the Pancreas Associated with Ectopic Splenic Island. PMID- 17866712 TI - Transactions of the New York Surgical Society-Stated Meeting October 28, 1931. PMID- 17866713 TI - Ruptured Gangrenous Caecum. PMID- 17866714 TI - Management of Skull Fracture involving the Frontal Sinus. PMID- 17866715 TI - Osteomyelitis of the Jaws in Nurslings and Infants. PMID- 17866716 TI - Rontgen Visualization of the Parotid Gland by Means of Lipiodol Injection. PMID- 17866717 TI - Primary Tuberculosis of the Parotid Gland. PMID- 17866718 TI - Metastatic Epidural Abscess of the Spinal Cord and Recovery after Operation. PMID- 17866719 TI - Pulmonary Embolism and Infarction: Analysis of Sixty-Four Verified Cases. PMID- 17866721 TI - Acute Fractures of the Pelvis: Based on Eighty-One Collected Cases. PMID- 17866720 TI - Nerve Suture and Muscle Repair: Primary Suture of the Ulnar Nerve and Secondary Reconstruction of the Extensor Tendons of the Forearm. PMID- 17866722 TI - Hemipelvectomy. PMID- 17866724 TI - Infra-Papillary Gastroduodenostomy by Mobilization with Retromesenteric Displacement of the Duodenum and Jejunum. PMID- 17866723 TI - Congenital Hypertrophic Pyloric Stenosis in Infancy. PMID- 17866725 TI - Hemophilic Arthritis: Bleeder's Joints. PMID- 17866726 TI - Congenital Cysts and Fistulae of the Neck. PMID- 17866727 TI - Comparative Study of Antiseptics in Experimentally Produced Local Infections. PMID- 17866728 TI - Transactions of the New York Surgical Society-Stated Meeting, November 11, 1931. PMID- 17866729 TI - Transactions of the New York Surgical Society-Stated Meeting, November 25, 1931. PMID- 17866730 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting, October 5, 1931. PMID- 17866731 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting, November 2, 1931. PMID- 17866732 TI - Brief Communications. PMID- 17866734 TI - Charles N. Dowd, M.D., 1858-1931. PMID- 17866733 TI - Norman Bruce Carson, M.D., 1844-1931. PMID- 17866735 TI - The Clinical Significance and Application of Histologic Grading of Cancers. PMID- 17866736 TI - A Bacteriological Study of Chronic Ulceration in Relation to Carcinoma. PMID- 17866737 TI - Results of Operations at the Johns Hopkins Hospital for Cancer of the Breast: Performed at the Johns Hopkins Hospital from 1889 to 1931. PMID- 17866738 TI - Operative Results in Cancer of the Breast: Thirty-Two Years' Experience. PMID- 17866739 TI - The Results of Treatment of Mammary Carcinoma at the Memorial Hospital: By Surgical and Irradiation Methods at the Memorial Hospital, New York City, During the Decade 1916 to 1926. PMID- 17866740 TI - Stereoscopic Rontgenography of the Breasts: An Aid in Establishing the Diagnosis of Mastitis and Carcinoma. PMID- 17866741 TI - Sarcoma of the Breast: A Report of Seven Cases. PMID- 17866742 TI - Cancer in Army Veterans. PMID- 17866743 TI - Gastrectomy: An Experimental Study. PMID- 17866744 TI - Carcinoma in the Duodenum: Originating from Aberrant Pancreatic Cells. PMID- 17866745 TI - Brief Communications. PMID- 17866746 TI - A History of Thyroid Surgery. PMID- 17866748 TI - Nodular Goitre. PMID- 17866747 TI - Thyroiditis. PMID- 17866749 TI - Lingual Thyroid. PMID- 17866750 TI - Cardiac Features of Goitre: With Special Reference to Operation. PMID- 17866751 TI - The Use of Potassium Iodide in Hyperthyroidism. PMID- 17866752 TI - A Simplified Technic in Thyroidectomy. PMID- 17866754 TI - Thyroid Crisis. PMID- 17866753 TI - How Much Thyroid Tissue Should be Removed in Toxic Goitre? PMID- 17866755 TI - Malignant Tumors and Tumor-like Growths of the Thymic Region. PMID- 17866756 TI - Suturing Wounds of the Heart. PMID- 17866757 TI - The Effect of Arteriovenous Aneurisms upon the Heart: With the Report of a Case Studied by Professor Rudolph Matas, Dr. Georger Herrmann, and the Author. PMID- 17866759 TI - Brief Communications. PMID- 17866758 TI - Cancer of the Colon and of the Rectum: Personal Experiences from 1892 to 1932. PMID- 17866760 TI - Memoir: John B. Deaver, M.D., Born July 25, 1855-Died September 25, 1931. PMID- 17866761 TI - The Repair of Cleft Palate: Concerning the Palatine Insertion of the Superior Constrictor Muscle of the Pharynx and its Significance in Cleft Palate; with Remarks on the "Push-Back Operation". PMID- 17866762 TI - The Pre-operative and Post-operative Care of Congenital Clefts of the Lip and Palate. PMID- 17866763 TI - Transthoracic Extrapleural Thoracotomy. PMID- 17866764 TI - Pulmonary Abscess. PMID- 17866765 TI - Phrenisectomy in the Treatment of Pulmonary Tuberculosis. PMID- 17866766 TI - The Repair of Intestinal Fistulae. PMID- 17866767 TI - Intestinal Fistulae: A Method for Preventing Digestion of the Skin. PMID- 17866768 TI - The Prevention of Faecal Fistula after Appendectomy: Simple Ligation vs. Precarious Purse-String. PMID- 17866770 TI - The Injection Treatment of Varicose Veins. PMID- 17866769 TI - Congenital Unilateral Renal Agenesia. PMID- 17866771 TI - Sodium Morrhuate as a Sclerosing Agent in the Treatment of Varicose Veins. PMID- 17866772 TI - Varicose Veins and Their Treatment: With a Study of Three Hundred Fifty-Four Cases. PMID- 17866773 TI - Varico-Phlebitis and the Injection Treatment. PMID- 17866774 TI - The Relation of Chronic Varicose Ulcer to Epithelioma: Based on Records of Over 1,000 Chronic Leg Ulcers. PMID- 17866776 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting, December 7, 1931. PMID- 17866775 TI - The Problem of Delayed Union and Ununited Fracture. PMID- 17866777 TI - Brief Communications. PMID- 17866778 TI - Memoir: Harry Clay Deaver, M.D., 1861-1931. PMID- 17866779 TI - Acute Intestinal Obstruction at the Los Angeles Hospital: An Analysis of Two Hundred and Sixty-Six Cases Treated in the Los Angeles County General Hospital. PMID- 17866781 TI - Acute Intestinal Obstruction at the Lebanon Hospital: A Report of One Hundred and Eighty-Five Cases Treated in the Lebanon Hospital of New York City. PMID- 17866780 TI - Acute Intestinal Obstruction at the New York Hospital: A Report of Two Hundred and Thirty-Five Cases. PMID- 17866782 TI - Acute Intussusception at the Philadelphia Children's Hospital: With Special Reference to Treatment by Resection of the Bowel Observations on Thirty-Four Cases Admitted to the Children's Hospital in Philadelphia. PMID- 17866784 TI - Congenital Duodenal Adhesions. PMID- 17866783 TI - Massive Resections in Acute Mechanical Intestinal Obstruction. PMID- 17866785 TI - Strangulation of the Sigmoid Flexure by the Pedicle of an Ovarian Cyst. PMID- 17866786 TI - The Treatment of Ileus: As Indicated by Clinical Experience and Experimental Studies. PMID- 17866787 TI - Lymphosarcoma of the Small and Large Intestines. PMID- 17866788 TI - Complications Associated with Major Proctectomy. PMID- 17866789 TI - Transactions of the New York Surgical Society-Stated Meeting, January 13, 1923. PMID- 17866790 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting, January 4, 1932. PMID- 17866791 TI - Brief Communications. PMID- 17866792 TI - Treatment of Fractures of the Neck of the Femur. PMID- 17866793 TI - The Kerr Technic in Resections of the Colon. PMID- 17866794 TI - Transactions of the New York Surgical Society-Stated Meeting January 27, 1932. PMID- 17866795 TI - Transactions of the Philadelphia Academy of Surgery and the New York Surgical Society-Conjoint Meeting, February 10, 1932. PMID- 17866796 TI - Brief Communications. PMID- 17866797 TI - Knee-joint Arthrotomy. PMID- 17866798 TI - An Operation for Recurrent Inferior Radioulnar Dislocation. PMID- 17866799 TI - A Study of the Cause of Death Following Burns. PMID- 17866801 TI - Embolectomy with Partial Arterial Occlusion for Embolism of the Extremities. PMID- 17866800 TI - Embolectomy: Report of a Case Involving the Femoral Artery. PMID- 17866803 TI - On the Mortality Resulting from Surgical Treatment of Chronic Gall-bladder Disease in Diabetes Mellitus. PMID- 17866804 TI - Fat Embolism. PMID- 17866802 TI - Insulin and Surgery. PMID- 17866806 TI - Acute Intussusception in Infancy and Childhood: A Review of Sixty-Four Cases. PMID- 17866805 TI - One Thousand Spinal Anaesthesias: With Special Reference to Complications and Mortality. PMID- 17866807 TI - Pericolic Membranes. PMID- 17866808 TI - Penetrating Wounds of the Abdomen: Reporting Sixty-Three Cases Received from Pistol, Rifle and Shotgun Missiles. PMID- 17866809 TI - The Influence of Haemorrhage in Abdominal Gunshot Injuries. PMID- 17866810 TI - Partial and Total Devascularization of the Stomach. PMID- 17866811 TI - The Vagus Nerve and Its Relation to Peptic Ulcer. PMID- 17866812 TI - Recurrent Perforation of Peptic Ulcers. PMID- 17866813 TI - Resection of the Fundus of the Stomach for Peptic Ulcer. PMID- 17866814 TI - Peptic Ulcer in Infants under One Year of Age. PMID- 17866815 TI - Partial Gastrectomy for Lymphosarcoma in Childhood. PMID- 17866816 TI - Pseudomyxoma Peritonei. PMID- 17866817 TI - Chronic Obstruction of the Duodenum Caused by Enlarged Retroperitoneal Glands. PMID- 17866819 TI - Perforated Peptic Ulcer of Meckel's Diverticulum. PMID- 17866818 TI - Gravity Feeding by Jejunostomy. PMID- 17866820 TI - Benign Tumors of the Stomach. PMID- 17866821 TI - Advanced Gastrojejunal Ulcer. PMID- 17866822 TI - The Choice of Surgical Procedures for Duodenal Ulcer. PMID- 17866823 TI - Tumors of the Small Intestine. PMID- 17866825 TI - Perimesenteric Intra-Abdominal Hernia. PMID- 17866824 TI - Late Results in the Operative Treatment of Carcinoma of the Breast. PMID- 17866827 TI - Automobile Rupture of the Intestines. PMID- 17866826 TI - Transactions of the New York Surgical Society-Stated Meeting, February 24, 1932. PMID- 17866828 TI - A Study of Mesenteric Cysts: With a Report of Two Recent Cases. PMID- 17866830 TI - Sodium Ricinoleate: Its Possible Value in the Prevention and Treatment of Peritonitis. PMID- 17866829 TI - Mesenteric and Omental Cysts. PMID- 17866831 TI - Internal Hernia following Gastro-enterostomy. PMID- 17866833 TI - X-ray Diagnosis of Acute Intestinal Obstruction without the use of Contrast Media. PMID- 17866832 TI - Posterior Pituitary Extract in the Prevention of Post-Operative Intestinal Distension: A Preliminary Report. PMID- 17866834 TI - Carcinoma of the Hepatic Duct. PMID- 17866836 TI - The Relation of the Blood Fibrin to the Haemorrhagic Diathesis of Obstructive Jaundice. PMID- 17866837 TI - The Surgical Treatment Active Cholecystitis. PMID- 17866835 TI - The Prediction of Haemorrhage in Obstructive Jaundice. PMID- 17866838 TI - Calcification of the Gall-Bladder. PMID- 17866839 TI - Acute Pancreatic Necrosis and Its Sequelae: A Critical Study of Thirty Cases. PMID- 17866840 TI - Chronic Interlobular Pancreatitis. PMID- 17866842 TI - The Etiology of Inflammatory and Degenerative Diseases of the Appendix. PMID- 17866841 TI - Post-Operative Shock following Splenectomy for Chronic Thrombocytopenic Purpura. PMID- 17866843 TI - Myxoglobulosis of the Appendix. PMID- 17866844 TI - Brief Communications. PMID- 17866845 TI - ADDRESS OF THE PRESIDENT: SURGERY OF THE SYMPATHETIC NERVOUS SYSTEM. PMID- 17866846 TI - CARCINOMA OF THE MOUTH AND TONGUE. PMID- 17866847 TI - THE PATHOGENESIS AND SYMPTOMS OF CHRONIC OBLITERATIVE APPENDICITIS. PMID- 17866848 TI - ACUTE APPENDICITIS-A BRIEF CRITICISM. PMID- 17866849 TI - TREATMENT OF APPENDICITIS COMPLICATED BY PERITONITIS. PMID- 17866850 TI - CLOSING VERY LARGE HERNIAL OPENINGS. PMID- 17866851 TI - ABDOMINAL INCISIONS AND THEIR CLOSURE. PMID- 17866853 TI - THE SURGICAL TREATMENT OF HAEMORRHAGIC DUODENAL ULCER. PMID- 17866852 TI - HERNIA OF THE URETER. PMID- 17866854 TI - CARCINOMA OF THE STOMACH-AN ANALYTICAL SURVEY. PMID- 17866856 TI - THE MECHANISM OF CHOLESTEROL GALL-STONE FORMATION. PMID- 17866855 TI - CALCIUM CARBONATE GALL-STONES AND THEIR EXPERIMENTAL PRODUCTION. PMID- 17866857 TI - TUBERCULOSIS OF THE THYROID GLAND. PMID- 17866858 TI - PARATHYROIDISM. PMID- 17866859 TI - ANEURISM OF THE INNOMINATE ARTERY. PMID- 17866860 TI - SUBCLAVIAN ANEURISM. PMID- 17866861 TI - SURGICAL TREATMENT OF POST-OPERATIVE SAPHENOUS THROMBOPHLEBITIS. PMID- 17866862 TI - AZYGOS VENOUS SYSTEM IN ITS RELATION TO SEPSIS. PMID- 17866863 TI - THE INTRAVENOUS INJECTION OF SCLEROSING SUBSTANCES: EXPERIMENTAL COMPARATIVE STUDIES OF CHANGES IN THE VESSELS. PMID- 17866865 TI - THE GENERAL CARE OF PERIPHERAL VASCULAR DISEASES. PMID- 17866864 TI - THE DIFFERENTIATION OF SPASTIC FROM ORGANIC PERIPHERAL VASCULAR OCCLUSION BY THE SKIN-TEMPERATURE RESPONSE TO HIGH ENVIRONMENTAL TEMPERATURE. PMID- 17866866 TI - OBSERVATIONS ON SYMPATHETIC VASOMOTOR PATHWAYS. PMID- 17866868 TI - SURGICAL TREATMENT OF CERTAIN VASCULAR DISORDERS BY SYMPATHECTOMY. PMID- 17866867 TI - THE QUANTITATIVE DETERMINATION OF VASOCONSTRICTOR SPASM AS A BASIS FOR THERAPY IN PERIPHERAL ARTERIAL DISEASES. PMID- 17866869 TI - RAYNAUD'S DISEASE, THROMBO-ANGIITIS OBLITERANS AND SCLERODERMA: SELECTION OF CASES FOR AND RESULTS OF SYMPATHETIC GANGLIONECTOMY AND TRUNK RESECTION. PMID- 17866870 TI - THE TREATMENT OF TRIGEMINAL NEURALGIA BY THE CEREBELLAR ROUTE. PMID- 17866871 TI - THE INFREQUENCY OF CARCINOMA OF THE CERVIX WITH COMPLETE PROCIDENTIA. PMID- 17866872 TI - Splenectomy in Purpura Hemorrhagica. PMID- 17866873 TI - The Tumors of the Sternum: Report of Removal of a Large Mediastinal Sternal Chondromyxoma. PMID- 17866875 TI - The Cancer Problem in the General Hospital. PMID- 17866874 TI - The Surgical Treatment of Mediastinal Tumors: Removal of Cystic Azygos Lobe from Posterior Mediastinum. PMID- 17866876 TI - Temporary Bilateral Abductor Paralysis without Nerve Injury and Tetany following Thyroidectomy. PMID- 17866877 TI - Results Obtained in the Treatment of Raynaud's Disease by Sympathetic Neurectomy and in Thrombo-angiitis Obliterans by Desensitization of Peripheral Sensory Nerves. PMID- 17866878 TI - Results of Operative Treatment of Cancer of the Breast. PMID- 17866879 TI - When Should Irradiation with Radium or X-ray Precede Operation or be Employed without Operation? PMID- 17866881 TI - Ulceration of Aberrant Gastric Mucosa in Meckel's Diverticulum: As a Source of Intestinal Haemorrhage. PMID- 17866880 TI - Inoperable and Malignant Tumors. PMID- 17866882 TI - Clinical Aspects and Treatment of Primary Lymphosarcoma of the Stomach and Intestines. PMID- 17866883 TI - The Fate of the Obstructed Loop in Intestinal Obstruction following an Anastomosis around the Obstruction without Resection. PMID- 17866884 TI - Maggots and Osteomyelitis. PMID- 17866885 TI - Fracture of the Neck of the Femur: Clinical Criteria in Prognosis. PMID- 17866887 TI - Malignant Tumors of the Kidney in Infancy and Childhood. PMID- 17866886 TI - Tuberculosis of the Upper Segment of a Duplicated Kidney. PMID- 17866888 TI - Sarcoma of the Kidney of the Adult: A Review of Twenty Cases with a Report of a Case. PMID- 17866890 TI - Post-Pyloric Ulcer under the Therapeutic Management of Internist, Radiologist and Surgeon. PMID- 17866889 TI - Stannoxyl in the Treatment of Chronic Recurring Osteomyelitis. PMID- 17866891 TI - The Length and Position of the Vermiform Appendix: A Study of 4,680 Specimens. PMID- 17866892 TI - Surgical Possibilities in the Treatment of Anterior Poliomyelitis. PMID- 17866893 TI - Operative Treatment of Paralytic Genu Recurvatum. PMID- 17866895 TI - Krukenberg Tumor of the Ovary. PMID- 17866894 TI - Chronic Tuberculous Polyarthritis. PMID- 17866896 TI - Treatment of Pott's Fracture: Report Based on Fifty Cases. PMID- 17866897 TI - Progressive Post-operative Cutaneous Gangrene. PMID- 17866898 TI - Radical Operations for Carcinoma of the Breast: A Preliminary Excision of the Tumor or Ablation of the Breast. PMID- 17866899 TI - Traumatic Lesions of Arteries, Indications for Therapeutic Ligation of Veins. PMID- 17866900 TI - Frank L. Hupp, M.D., 1929. PMID- 17866901 TI - Walter Aikman Sherwood, M.D., 1875-1931. PMID- 17866902 TI - The Fissures of the Lungs. PMID- 17866904 TI - Salivary Calculi. PMID- 17866903 TI - Lingual Thyroid. PMID- 17866905 TI - Acute Empyaema of Thorax: The Immediate and Late Results in a Hundred Consecutive Cases. PMID- 17866906 TI - Orbital Myositis and Choked Disc in Exophthalmic Goitre. PMID- 17866907 TI - Perinephritic Abscess. PMID- 17866908 TI - Cysticercus of the Brain. PMID- 17866910 TI - Transactions of the New York Surgical Society-Stated Meetings March 9, 1932. PMID- 17866909 TI - Chondroma of the Intervertebral Disks. PMID- 17866912 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting March 7, 1932. PMID- 17866911 TI - Transactions of the New York Surgical Society-Stated Meetings April 13, 1932. PMID- 17866914 TI - Emory Alexander, M.D., 1880-1930. PMID- 17866913 TI - Willy Meyer, M.D., 1858-1932. PMID- 17866915 TI - Primary Haemangioma of the Spine. PMID- 17866916 TI - Post-Traumatic Painful Osteoporosis. PMID- 17866917 TI - Irradiation in Carcinoma of the Breast. PMID- 17866918 TI - Sarcoma of the Stomach. PMID- 17866920 TI - Pilonidal Sinus. PMID- 17866919 TI - Partial Hysterectomy and the Use of the Stump of the Uterus to Support the Bladder in the Vaginal Operation for Prolapse. PMID- 17866921 TI - Syphilitic Leg Ulcers: Clinical Features Presented by 100 Cases. PMID- 17866922 TI - Treatment of Fractures in the Cincinnati General Hospital. PMID- 17866923 TI - The Treatment of Joint Fractures. PMID- 17866924 TI - Late Results of Separation of an Epiphysis. PMID- 17866926 TI - End-Results of Carpal-Scaphoid Fractures. PMID- 17866925 TI - Fractures of the Head and Neck of the Radius. PMID- 17866927 TI - Reconstructive Operation for Non-reducible Fractures of the Head of the Humerus. PMID- 17866929 TI - Intracapsular Fractures of the Neck of the Femur: A Closed Double-Screw Method for Reduction and Fixation-Preliminary Report. PMID- 17866928 TI - Elephantiasis Nostra. PMID- 17866931 TI - The Full-Thickness Skin Graft: Its Field of Applicability and Technical Considerations. PMID- 17866930 TI - Localized Tuberculosis of the Chest-Wall. PMID- 17866932 TI - Transactions of the New York Surgical Society-Stated Meeting April 27, 1932. PMID- 17866933 TI - Transactions of the Philadelphia Academy Surgery-Stated Meeting April 4, 1932. PMID- 17866934 TI - Brief Communications. PMID- 17866935 TI - Dead Bone Grafts to Repair Skull Defects. PMID- 17866936 TI - Studies on Acute Cranial and Intracranial Injuries. PMID- 17866937 TI - Chemical Treatment of the Periosteum in Thoracoplasty to Inhibit Rib Regeneration. PMID- 17866938 TI - Longitudinal Bone Growth: The Influence of Sympathetic Deinnervation. PMID- 17866939 TI - Interscapulo-Thoracic Amputation for Secondarily Infected Tuberculosis of Shoulder. PMID- 17866940 TI - Recurring External Dislocations of the Patella. PMID- 17866942 TI - Subcutaneous Angiomas of the Breast. PMID- 17866941 TI - The Treatment of Mal-union Following Unreduced Potts' Fracture. PMID- 17866943 TI - The Effect of Blood in Experimental Peritonitis. PMID- 17866945 TI - The Treatment of Sarcoma of the Long Bones. PMID- 17866944 TI - Traumatic Ulnar Neuritis: With Especial Reference to the Late or Tardy Ulnar Paralysis. PMID- 17866946 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting May 2, 1932. PMID- 17866947 TI - Astley Paston Cooper Ashhurst, M.D., 1876-1932. PMID- 17866948 TI - David Barrow, M.D., 1858-1932. PMID- 17866949 TI - William Williams Keen, M.D., 1837-1932. PMID- 17866950 TI - Effects of Sympathetic Nerve Surgery in Certain Intestinal Conditions. PMID- 17866951 TI - The Surgery of the Sympathetic Nervous System: Operative Notes Based on 273 Operations. PMID- 17866953 TI - Intermittent Claudication without Gangrene Controlled by Sympathetic Nerve Block. PMID- 17866952 TI - The Surgical Aspects of the Autonomic Nervous System. PMID- 17866954 TI - Phrenic Neurectomy: Results in 100 Cases. PMID- 17866955 TI - Bronchoscopical Observations on Post-Operative Pulmonary Complications. PMID- 17866956 TI - Penetrating Stab Wounds and Bullet Wounds of the Chest: A Study of Sixty-Eight Cases Operated Upon between June 1, 1931, and April 30, 1932, with a Description of a New Operative Procedure of Extrapleuralization and Exteriorization of the Pulmonary Laceration. PMID- 17866957 TI - Cardiorrhaphy in Wounds of the Heart. PMID- 17866958 TI - Jejunostomy: A Clinical and Experimental Study of the Technic of the Operation. PMID- 17866959 TI - Avertin Anaesthesia: A Study of 431 Cases Compared with 431 Similar Cases Operated on Under Other Types of Anaesthesia, at the Brooklyn Hospital. PMID- 17866960 TI - Transactions of the New York Surgical Society-Stated Meetings, May 11, 1932. PMID- 17866961 TI - Transactions of the New York Surgical Society-Stated Meetings, October 12, 1932. PMID- 17866963 TI - Brief Communications. PMID- 17866962 TI - Transactions of the New York Surgical Society-Stated Meetings, October 31, 1932. PMID- 17866964 TI - An Evaluation of the Tannic-Acid Treatment of Burns. PMID- 17866965 TI - The Treatment of Old Unhealed Burns. PMID- 17866966 TI - A Study in Extensive Cutaneous Burns. PMID- 17866967 TI - Arm-Chest Adhesions and Their Plastic Reconstruction: By the Tube Flap Method. PMID- 17866968 TI - Artifical Inguinal Hernia. PMID- 17866969 TI - Hernia Into the Prevesical Space. PMID- 17866970 TI - Intersigmoid Hernia. PMID- 17866971 TI - Strangulated Femoral Hernia: Anatomy and Surgical Treatment. PMID- 17866972 TI - Strangulated Femoral Cystocele. PMID- 17866973 TI - Osteomyelitis of the Skull. PMID- 17866974 TI - The Use of Continuous Intravenous Infusions in Acute Abdominal Crises. PMID- 17866975 TI - Tropacocaine Hydrochloride in Spinal Anaesthesia: Observations Based on One Thousand Operations. PMID- 17866976 TI - Torsion of the Omentum. PMID- 17866978 TI - Transactions of the New York Surgical Society-Stated Meeting held November 9, 1932. PMID- 17866977 TI - Bilateral Snapping Thumbs. PMID- 17866979 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting held October 3, 1932. PMID- 17866980 TI - Brief Communications. PMID- 17866981 TI - Electrosurgery: A Clinical Report on 118 Operations. PMID- 17866983 TI - Multiple Myeloma Simulating Hyperparathyroidism. PMID- 17866982 TI - The Diagnosis and Operative Control of Acute Pyogenic Phlebitis Complicated by General Septic Invasion. PMID- 17866984 TI - Anomaly of the Inferior Laryngeal Nerve. PMID- 17866985 TI - Amount of Gland to be Left at Thyroidectomy. PMID- 17866986 TI - Skin Conservation in Radical Mastectomy for Carcinoma. PMID- 17866988 TI - Primary Jejunal Ulcer. PMID- 17866987 TI - Observations on Rupture of the Supraspinatus Tendon: Based Upon a Study of Seventy-Three Cadavers. PMID- 17866989 TI - The Results of Medical and Surgical Treatment of Peptic Ulcer. PMID- 17866990 TI - Clinical and Pathological Factors Influencing Ultimate Prognosis following Resection for Carcinoma of the Stomach. PMID- 17866991 TI - Inflammatory Tumors of the Gastro-Intestinal Tract. PMID- 17866992 TI - Primary Mucoid Carcinoma of the Rectum in a Thirteen-Year-Old Girl. PMID- 17866994 TI - Transactions of the New York Surgical Society-Stated Meeting held November 23, 1932. PMID- 17866993 TI - Ectopic Chorionepithelioma: Report of Case in which the Lesion was Situated in the Jejunum. PMID- 17866995 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting held November 7, 1932. PMID- 17866996 TI - X-ray Common Duct Stones. PMID- 17866997 TI - Memoir: George Howard Monks, M.D., 1853-1933. PMID- 17866999 TI - Congenital Absence of Testes (Anorchia). PMID- 17866998 TI - Surgery of Diabetic Gangrene. PMID- 17867000 TI - Extravesical Ureteral Opening Causing Urinary Incontinence. PMID- 17867002 TI - Post-Operative Urinary Retention. PMID- 17867001 TI - Infected Supernumerary Ureter and Pelvis of Kidney: Hemi-Nephrectomy. PMID- 17867004 TI - Transactions of the New York Surgical Society-Stated Meeting held December 14, 1932. PMID- 17867003 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting held December 5, 1932. PMID- 17867005 TI - Meckel's Diverticulum Perforation by a Fishbone. PMID- 17867006 TI - Embolectomy for Arterial Embolism of the Extremities. PMID- 17867007 TI - The Trendelenburg Operation for Pulmonary Embolism. PMID- 17867008 TI - Advances in the Diagnosis and Treatment of Thrombo-Angiitis Obliterans. PMID- 17867009 TI - Thrombo-Angiitis Obliterans: Relief of Pain by Peripheral Nerve Section. PMID- 17867010 TI - Peripheral Vasoconstriction by Tobacco and Its Relation to Thrombo-Angiitis Obliterans. PMID- 17867011 TI - Basis for Recurrence of Varices in the Various Forms of Thrombophlebitis. PMID- 17867012 TI - Renal Neoplasms: Report Based Upon Twenty-Five Cases of Malignant Tumors of the Kidney. PMID- 17867013 TI - Annular Gastrectomy: Further Observations on the Cause of Its Failure. PMID- 17867014 TI - Tumors of the Stomach. PMID- 17867015 TI - Tumors of the Duodenum. PMID- 17867016 TI - Double Primary Malignant Tumors of the Colon. PMID- 17867018 TI - Perforated Peptic Ulcer in German Clinics: An Analysis of 4,402 Cases. PMID- 17867017 TI - Acute Obstruction of the Duodenum due to Submucous Haematoma. PMID- 17867019 TI - Acute Perforated Gastric and Duodenal Ulcers. PMID- 17867020 TI - Total Gastrectomy. PMID- 17867021 TI - Cardiospasm: Diagnosis and Treatment. PMID- 17867022 TI - External Duodenal Fistula. PMID- 17867023 TI - The Excoriations Around External Gastro-intestinal Fistula: Experimental Studies on Their Etiology and Further Experience with the Kaolin Powder Treatment. PMID- 17867024 TI - Arterial Embolectomy. PMID- 17867026 TI - Transactions of the New York Surgical Society-Stated Meeting held January 11, 1933. PMID- 17867025 TI - Surgical Diseases of the Shoulder Bursae. PMID- 17867027 TI - Transactions of the Philadelphia Academy of Surgery-Meeting held January 2, 1933. PMID- 17867028 TI - Transactions of the New York Surgical Society and the Philadelphia Academy of Surgery-Joint Meeting held February 8, 1933. PMID- 17867029 TI - Brief Communications. PMID- 17867030 TI - Gall-Bladder Surgery: A Report of Two Hundred Consecutive Operated Cases of Gall Bladder Disease. PMID- 17867031 TI - Improved Gall-Bladder Technic: With Especial Reference to Omission of Drainage. PMID- 17867032 TI - Correlation of Symptoms, Pathology and Results in Cholecystectomy: A Study of Two Hundred Thirty-Three Cholecystectomies Done in Vanderbilt School of Medicine from 1925 to the Middle of May, 1932. PMID- 17867033 TI - Conservation of Hepatic Function in Gall-Bladder Operations: Precautionary Measures to Prevent "Liver Deaths". PMID- 17867034 TI - Syndrome of Chronic Cholecystitis. PMID- 17867035 TI - Perforation of the Gall-Bladder in Acute Cholecystitis. PMID- 17867037 TI - Resection of Common Biliary Duct for Carcinoma of Ampulla of Vater. PMID- 17867036 TI - Incidental Gall-Stones in Women. PMID- 17867038 TI - Cysticoduodenostomy: An Experimental Study. PMID- 17867039 TI - Spontaneous External Rupture of Empyema of Gall-Bladder. PMID- 17867040 TI - Removal of the Spleen. PMID- 17867041 TI - Pilonidal Cyst. PMID- 17867042 TI - Healing of Surface Wounds to Prevent Deformities. PMID- 17867043 TI - Leeches in Phlebitis to Prevent Pulmonary Embolism. PMID- 17867044 TI - Arterial Embolectomy. PMID- 17867046 TI - Transactions of the New York Surgical Society-Stated Meeting held January 25, 1933. PMID- 17867045 TI - Jones Splint Fracture Neck of Femur. PMID- 17867047 TI - Transactions of the New York Surgical Society-Stated Meeting held February 24, 1933. PMID- 17867048 TI - Brief Communications. PMID- 17867049 TI - ADDRESS OF THE PRESIDENT: THE STUDY AND TEACHING AND THE PRACTICE OF SURGERY. PMID- 17867050 TI - UNDESCENDED TESTICLE: A COMPARISON OF THE END-RESULTS OF TOREK'S OPERATION AS CONTRASTED WITH THE FORMER METHODS OF OPERATION. PMID- 17867051 TI - OMBREDANNE'S POUCH OPERATION FOR HYPOSPADIAS. PMID- 17867053 TI - TUMORS OF THE BONY CHEST-WALL: A STUDY OF TWENTY-TWO PERSONAL AND SEVENTY-EIGHT COLLECTED CASES SINCE 1921. PMID- 17867052 TI - PRINCIPLES versus DETAILS IN THE TREATMENT OF ACUTE EMPYEMA. PMID- 17867054 TI - COMPLICATED CONTRACTURES OF THE HAND; THEIR TREATMENT BY FREEING FIBROSED TENDONS AND REPLACING DESTROYED TENDONS WITH GRAFTS. PMID- 17867055 TI - TRANSTHORACIC ABDOMINAL HERNIA. PMID- 17867056 TI - DUODENAL STASIS: DUODENO-JEJUNOSTOMY. PMID- 17867057 TI - THE TRAGEDY OF GASTRIC CARCINOMA: A STUDY OF 200 SURGICAL CASES. PMID- 17867058 TI - THE TEN-YEAR SURVIVORS OF RADICAL MASTECTOMY. PMID- 17867059 TI - THE INCIDENCE AND MANAGEMENT OF STONES IN THE COMMON AND HEPATIC DUCTS. PMID- 17867060 TI - THE TREATMENT OF CANCEROUS OR POTENTIALLY CANCEROUS CERVICAL LYMPH-NODES. PMID- 17867061 TI - THE USE OF SILK IN THE REPAIR OF CLEAN WOUNDS. PMID- 17867063 TI - THE INTRAVENOUS ADMINISTRATION OF DEXTROSE IN RINGER'S SOLUTION: WITH PARTICULAR REFERENCE TO ITS USE IN ACUTE ABDOMINAL CONDITIONS. PMID- 17867062 TI - ACUTE POST-OPERATIVE OBSTRUCTION OF THE BOWELS DIAGNOSED BY THE FLAT RONTGENOGRAM. PMID- 17867064 TI - SUBCUTANEOUS INJURIES OF THE ABDOMEN. PMID- 17867065 TI - ACUTE INTESTINAL OBSTRUCTION IN THE NEGRO: REVIEW OF 347 CASES. PMID- 17867066 TI - ACUTE INTUSSUSCEPTION. PMID- 17867067 TI - MECKEL'S DIVERTICULUM IN ACUTE ABDOMINAL EMERGENCIES. PMID- 17867069 TI - ACUTE MASSIVE HAEMORRHAGE FROM DUODENAL ULCER. PMID- 17867068 TI - WANDERING SPLEEN WITH TORSION OF THE PEDICLE. PMID- 17867070 TI - PANCREATIC EMERGENCIES. PMID- 17867071 TI - THE ACUTE GALL-BLADDER AS A SURGICAL EMERGENCY. PMID- 17867072 TI - TREATMENT OF ACUTE CHOLECYSTITIS. PMID- 17867073 TI - ACUTE CHOLECYSTIC DISEASE. PMID- 17867075 TI - ACUTE OBSTRUCTING AND INFLAMMATORY LESIONS OF THE KIDNEYS AND THE URETERS. PMID- 17867074 TI - ACUTE UROLOGICAL EMERGENCIES, PAST AND PRESENT. PMID- 17867076 TI - ANATOMY ECLIPSED. PMID- 17867077 TI - The Thoracic Lipomas. PMID- 17867078 TI - The Treatment of Intercostal Neuralgia of the Abdominal Wall. PMID- 17867079 TI - Wrinkles and Recipes in Intestinal Surgery. PMID- 17867080 TI - The Action of Morphine on the Small Intestine and Its Clinical Application in the Treatment of Peritonitis and Intestinal Obstruction. PMID- 17867081 TI - Benign Encapsulated Tumors in the Lateral Ventricles of the Brain: Diagnosis and Treatment. PMID- 17867083 TI - Vestigial Mastitis: A Hitherto Unrecognized Syndrome. PMID- 17867082 TI - Origin and Course of Infection in Subphrenic Abscess. PMID- 17867084 TI - Skeletal Pathology of Endocrine Origin. PMID- 17867086 TI - Closure of the Abdomen with Through-and-Through Silver Wire Sutures in Cases of Acute Abdominal Emergencies. PMID- 17867085 TI - Emergency Complications Occurring after Operations on the Stomach and Duodenum and Their Treatment. PMID- 17867087 TI - Some Limitations of Enterostomy. PMID- 17867088 TI - Rupture of the Liver without Tear of the Capsule. PMID- 17867089 TI - Foreign Bodies in the Biliary Tract. PMID- 17867090 TI - Acute Surgical Lesions of the Pancreas. PMID- 17867091 TI - Blood Cyst of the Spleen: Intracapsular Rupture. PMID- 17867092 TI - Surgical Judgement in the Approach to the Acute Abdomen. PMID- 17867093 TI - Choked Leg. PMID- 17867094 TI - Pre-Operative Irradiation in Cases of Cancer the Breast with and without Biopsy. PMID- 17867095 TI - The On-End or Vertical Mattress Suture. PMID- 17867096 TI - The Water Requirements of Surgical Patients. PMID- 17867097 TI - Surgical Operations in Addison's Disease: Successful Epididymectomy and Orchidectomy for Tuberculosis. PMID- 17867098 TI - Spontaneous Pneumothorax. PMID- 17867099 TI - Lateral Aberrant Thyroid Glands. PMID- 17867100 TI - Prolapse of the Rectum. PMID- 17867101 TI - Pruritus Ani: Its Etiology and Treatment. PMID- 17867102 TI - Non-Specific Granulomata of the Intestines: Inflammatory Tumors and Strictures of the Bowel. PMID- 17867104 TI - Intussusception Due to Invaginated Meckel's Diverticulum: Report of Two Cases with a Study of 160 Cases Collected from the Literature. PMID- 17867103 TI - Enterostomy in Ileus. PMID- 17867105 TI - Synovectomy of the Knee-Joint in Chronic Arthritis. PMID- 17867106 TI - Situs Transversus Viscerum: Report of Case with Cholelithiasis. PMID- 17867107 TI - Mortality Following Gall-Bladder Surgery. PMID- 17867108 TI - William McDowell Mastin, M.D. 1853-1933. PMID- 17867109 TI - Walter Ellis Sistrunk, M.D. 1880-1933. PMID- 17867110 TI - Subphrenic Abscess: An Analysis of 3,372 Collected and Personal Cases. PMID- 17867111 TI - Injury as a Causative Factor in the Development of Malignant Tumors. PMID- 17867112 TI - ARTERIAL SUPPLY OF UPPER LIP PLASTIC. PMID- 17867113 TI - AIR EMBOLISM COMPLICATING THYROIDECTOMY. PMID- 17867114 TI - MALIGNANT NEOPLASMS OF THE THYROID GLAND. PMID- 17867115 TI - EXPERIMENTAL AND CLINICAL STUDIES OF THE RELATIONSHIP OF THYROID DISEASE AND PANCREATIC FUNCTION. II. PMID- 17867116 TI - STAB WOUNDS OF THE HEART. PMID- 17867117 TI - THE OPERATION OF CARDIOLYSIS IN ADHESIVE PERICARDITIS WITH PICK'S SYNDROME. PMID- 17867118 TI - SURGERY OF THE INFERIOR VENA CAVA: CLINICAL AND EXPERIMENTAL STUDIES. PMID- 17867119 TI - THE CAUSATION AND TREATMENT OF MULTIPLE ADENOMATOSIS OF THE COLON. PMID- 17867120 TI - SURGICAL TREATMENT OF VARICOCELE. PMID- 17867121 TI - GENITO-ANO-RECTAL LYMPHOGRANULOMATOSIS OF THE MALE. PMID- 17867123 TI - TRANSACTIONS OF THE PHILADELPHIA ACADEMY OF SURGERY : Stated Meeting Held May 1, 1933. PMID- 17867122 TI - RESTORATION OF HAND FUNCTION AFTER TRAUMATIC INJURY. PMID- 17867124 TI - BRIEF COMMUNICATIONS. PMID- 17867125 TI - DEATHS FROM APPENDICITIS: THE MORTALITY FROM APPENDICITIS AND THE CAUSES OF DEATH FOLLOWING APPENDICITIS. PMID- 17867127 TI - CANCER OF THE MOUTH. PMID- 17867126 TI - DISRUPTION OF ABDOMINAL WOUNDS: Symposium at the Meeting of the New York Surgical Society, November 8, 1933. PMID- 17867128 TI - EPITHELIOMA OF THE LIP: WITH PARTICULAR REFERENCE TO LYMPH-NODE METASTASES. PMID- 17867129 TI - PALATOPLASTY USING EXTRA-ORAL TISSUES. PMID- 17867130 TI - The Use of Fascia in Reconstructive Surgery: With Special Reference to Operative Technic. PMID- 17867131 TI - The Reaction of the Retroperitoneal Tissues to Infection. PMID- 17867132 TI - The Rationale of the Treatment of Chronic Osteomyelitis with Special Reference to Maggot Therapy. PMID- 17867133 TI - The Problem of Recurrent Hernia. PMID- 17867134 TI - Gunshot Wounds of the Abdomen: A Review of Twenty-Two Cases. PMID- 17867135 TI - Experimental Studies in Nerve Transplants. PMID- 17867136 TI - Further Experience in the Relief of Pain by Section of the Rami Communicantes and Ganglionated Sympathetic Cord. PMID- 17867137 TI - Syphilis of the Clavicle. PMID- 17867138 TI - Acute Pancreatitis. PMID- 17867139 TI - Study of the Blood-Platelets after Removal of a Ruptured Spleen. PMID- 17867141 TI - Operative Mortality in Intestinal Obstruction. PMID- 17867140 TI - Chronic Duodenal Ileus. PMID- 17867142 TI - Sarcomatoid Fibroma of the Skin: Progressive and Recurring Dermatofibroma. PMID- 17867143 TI - Arsenical Keratoses and Epitheliomas. PMID- 17867144 TI - Transactions of the New York Surgical Society-Stated Meeting held March 8, 1933. PMID- 17867145 TI - Transactions of the New York Surgical Society-Stated Meeting held March 22, 1933. PMID- 17867147 TI - George David Stewart, M.D. 1862-1933. PMID- 17867146 TI - Harvey Gilmer Mudd, M.D. 1857-1933. PMID- 17867148 TI - John Speese, M.D. 1880-1933. PMID- 17867149 TI - Jejunal Ulcer: Some Observations on its Complications and their Treatment. PMID- 17867150 TI - Osteochondritis Dissecans: Intra-Articular Osseocartilaginous Loose Bodies a Clinical Study Based Upon Ten Personally Observed Cases. PMID- 17867151 TI - Solitary Bone Cyst: The Localized from of Osteitis Fibrosa Cystica. PMID- 17867152 TI - Post-Traumatic Acute Bone Atrophy (Sudeck's). PMID- 17867153 TI - Dislocation of the Cervical Vertebrae: Report of a Case of Complete Forward Dislocation of the Sixth Cervical Vertebra with Reduction by Forcible Traction and Full Recovery. PMID- 17867154 TI - Osteochondromatosis of Elbow. PMID- 17867155 TI - Radial Paralysis Complicating Fracture and Dislocation in the Upper Limb. PMID- 17867156 TI - Fracture of the Capitellum of the Humerus. PMID- 17867157 TI - Colles' Fracture of the Radius: Observations on 188 Cases. PMID- 17867159 TI - Transactions of the New York Surgical Society-Stated Meeting held April 26, 1933. PMID- 17867158 TI - Pseudo-Arthrosis of the Hip Following Acute Infection of the Joint. PMID- 17867161 TI - Alexis Victor Moschowitz, M.D. 1865-1933. PMID- 17867160 TI - Brief Communications. PMID- 17867162 TI - Miles Fuller Porter, M.D. 1856-1933. PMID- 17867163 TI - The Klippel-Feil Syndrome. PMID- 17867164 TI - Histomine Therapy of Rheumatic Affections and Disturbances of the Peripheral Circulation. PMID- 17867165 TI - Indirect Inguinal Hernia in the Light of the Newer Interpretation of Anatomy. PMID- 17867167 TI - Peri-Anal Tuberculosis. PMID- 17867166 TI - Cysts and Sinuses of the Sacrococcygeal Region. PMID- 17867168 TI - Internal Haemorrhoids: Comparative Value of Treatment by Operative and by Injection Methods: A Survey of 62,910 Cases. PMID- 17867169 TI - Pre- and Post-Operative Management of Ano-Rectal Cases: An Inquiry into the Use of Certain Anaesthetic Agents. PMID- 17867170 TI - The Pulses of the Foot: Their Value in the Diagnosis of Peripheral Circulatory Disease. PMID- 17867171 TI - Disability Due to Swelling Following Trauma of the Extremities: Post-Traumatic Peri-Articular Fibrosis. PMID- 17867172 TI - The Stump of the Appendix, an Agent of Infection. PMID- 17867173 TI - Drainage After Operation for Appendicitis: Chiefly on the Removal of Drains. PMID- 17867174 TI - Appendicostomy in Cases of Ruptured Appendix Associated with Diffuse General Peritonitis. PMID- 17867175 TI - Differential Diagnosis of Abdominal Manifestations of Acute Rheumatic Fever from Acute Appendicitis. PMID- 17867176 TI - The Diagnosis of Phlebitis in Varicose Veins with the Aid of the Sedimentation Rate. PMID- 17867177 TI - Sclerosing Injections in Surgery. PMID- 17867178 TI - Aseptic End-to-Side Ileocolostomy: Clamp Method: Technic and Statistical Data. PMID- 17867180 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting held October 2, 1933. PMID- 17867179 TI - Transactions of the Philadelphia Academy of Surgery-Meeting held April 3, 1933. PMID- 17867181 TI - Transactions of the New York Surgical Society-Stated Meeting held October 11, 1933. PMID- 17867182 TI - Ligation of the Great Vessels of the Neck. PMID- 17867184 TI - Tuberculosis of the Breast. PMID- 17867183 TI - Asymmetrical Breast Deformities. PMID- 17867185 TI - Value of Nephrolysis, Ureterolysis and Nephropexy in Selected Cases. PMID- 17867186 TI - Primary Tumors of the Ureter with Special Reference to the Malignant Tumors: Report of Three Cases. PMID- 17867187 TI - Supernumerary Kidney. PMID- 17867188 TI - The Treatment of Varicose Veins: A Study Based Upon A Series of More Than 35,000 Injections of Various Sclerosing Solutions Given in 3,164 Cases, and 293 Cases of Extensive and Recurrent Varicose Veins Treated by Preliminary Ambulatory Ligation and Subsequent Injections. PMID- 17867189 TI - Transactions of the New York Surgical Society-Stated Meeting held April 12, 1933. PMID- 17867190 TI - Transactions of the New York Surgical Society-Stated Meeting held May 12, 1933. PMID- 17867191 TI - Transactions of the New York Surgical Society-Stated Meeting held October 25, 1933. PMID- 17867192 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meeting held March 6, 1933. PMID- 17867193 TI - Brief Communications. PMID- 17867194 TI - Fracture of Lower End of Humerus. PMID- 17867195 TI - Fractures of the Leg Below the Lower Third. PMID- 17867196 TI - Fractures of the Shaft of the Humerus. PMID- 17867197 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meetings held Nov. 6, 1933. PMID- 17867198 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meetings held Dec. 4, 1933. PMID- 17867199 TI - Transactions of the Philadelphia Academy of Surgery-Stated Meetings held Jan. 8, 1934. PMID- 17867201 TI - Important Factors in the Surgical Treatment of Cholecystitis. PMID- 17867200 TI - The Factors Leading to Death in Operations Upon the Gall-Bladder and Bile-Ducts. PMID- 17867202 TI - Acute Cholecystitis: A Study of 75 Proven Cases with Subsiding or Subsided Clinical Manifestations at the Time of Operation. PMID- 17867204 TI - Acute Free Perforation of the Gall-Bladder. PMID- 17867203 TI - Perforation of the Gall-Bladder. PMID- 17867205 TI - Acute Inflammation of the Gall-Bladder; Conservative Operative Treatment. PMID- 17867207 TI - The Rontgenological Localization of Spinal Subarachnoid Block by the Use of Air in the Subarachnoid Space. PMID- 17867206 TI - Primary Carcinoma of the Common Bile-Duct. PMID- 17867208 TI - Treatment of Tuberculous Empyema Complicated by Pyogenic Infection. PMID- 17867209 TI - Skeletal Muscle Sarcoma. PMID- 17867210 TI - Localized Chronic Ulcerative Ileitis. PMID- 17867211 TI - Anterior Hemipylorectomy for Aberrant Pancreatic Tissue of the Duodenum Diagnostic Difficulties. PMID- 17867212 TI - The Carotid Sinus as an Etiological Factor in Sudden Anaesthetic Death. PMID- 17867214 TI - Femoral Hydrocele. PMID- 17867213 TI - The Relation of Post-Operative Paralytic Ileus to Mortality in Acute Appendicitis. PMID- 17867215 TI - The Germicidal Effects of Tannic Acid: With and Without the Addition of Mercurial Antiseptics. PMID- 17867216 TI - The Treatment of Varicose Ulcers and Veins. PMID- 17867217 TI - Outbreak news. Cholera, Iraq. PMID- 17867218 TI - Laboratory surveillance for wild and vaccine-derived polioviruses, January 2006 June 2007. PMID- 17867219 TI - [The device DOLPHIN in the treatment of rhinosinusitis and in postoperative period in endonasal surgical interventions]. PMID- 17867220 TI - [A method of therapy in combination of tubo-otitis and acute rhinosinusitis]. PMID- 17867221 TI - The dynamics of social solidarity: the Danish welfare state, 1900-2000. PMID- 17867222 TI - Notice of retraction. PMID- 17867223 TI - Imaging the South Seas: thoughts on the sexual politics of paradise in Samoa. PMID- 17867224 TI - Phytophotodermatitis caused by contact with a fig tree (Ficus carica). AB - Two arborists presented acutely with blistering eruptions affecting their forearms, hands, and fingers. The previous day, both men had pruned branches from a large fig tree, Ficus carica, which had sustained damaged during a storm. The following morning, both complained of a burning discomfort which rapidly evolved into erythema and bullae on skin that had been in direct contact with the tree branches. These symptoms gradually resolved over 4 to 6 weeks. Although phytophotodermatitis from Ficus carica has been reported, it is often poorly recognised and there is a need to raise awareness amongst arborists, orchardists, forestry workers, gardeners, and health professionals. PMID- 17867225 TI - Urbane decay. PMID- 17867226 TI - [A case of a successful removal of a large foreign body of the trachea and bronchus]. PMID- 17867227 TI - [An unusual esophageal foreign body in a child]. PMID- 17867228 TI - [More information on thyroid aberration]. PMID- 17867229 TI - [Pareses and paralyses of the larynx in children: features of development and course, diagnosis and treatment]. PMID- 17867230 TI - The provision of public goods under Islamic law: origins, impact, and limitations of the waqf system. PMID- 17867231 TI - Least-desired index for assessing the effectiveness of grass riparian filter strips in improving water quality in an agricultural region. AB - Unprotected streams within the agricultural Midwest region of the United States are subject to sedimentation, nutrification, and agricultural chemicals. Grass riparian filter strips (GRFSs) have been implemented as a best management practice to minimize sedimentation and associated materials that are harmful to aquatic ecosystems; however, few studies have examined the benthic community response to GRFS installation. This study introduces a least-desired index (LDI) multimetric approach of evaluating benthic communities in response to GRFS installation. LDI was determined in a reciprocal fashion to that of a benthic macroinvertebrate index of biotic integrity (B-IBI). When reference conditions are not available for the use of B-IBI, anti-reference sites, representing least desired conditions, can be used in constructing an LDI. A B-IBI and LDI were constructed in the Claypan Till Plains Subsection of Missouri and comparatively used to evaluate two test sites where tall fescue GRFS were installed. Five metrics were used to develop the B-IBI and six for the LDI. The LDI tended to be more conservative at evaluation in comparison to the B-IBI. Paired t-tests showed that LDI and B-IBI were significantly different at scoring test sites. The LDI assessed both test sites as showing no response to GRFS installation, whereas the B-IBI suggested moderate improvement. The LDI was considered to be a better index for evaluation because the streams used to develop the B-IBI were not suitable reference sites. An argument for the use of chironomid based metrics in low gradient agricultural streams is presented. PMID- 17867232 TI - The psychobiology of aggressive behaviour. AB - Among psychiatric illnesses, genetically determined disorders usually have an early onset and a severe and complicated course. Gene-environmental interaction is of importance for aggressive impulsive behaviour. For example, alcoholism type II has a high family loading, a severe course, and is often associated with antisocial behaviour. In order to gain further understanding of aggressive and impulsive behaviour, genes determining serotonin metabolism, neurosteroids and carbohydrate metabolism should be of interest to investigate. Furthermore, modern brain-imaging studies will reveal the site of action of aggressiveness and impulsivity. Within brain regions of interest, biological studies will promote our knowledge of this deleterious behaviour. PMID- 17867233 TI - Individual behaviours and substance use: the role of price. AB - I discuss economic approaches to the demand for harmfully addictive substances with an emphasis on the role of money prices. First, I examine trends in the real prices and in the prevalence of the use of cigarettes, alcohol, cocaine, heroin, and marijuana in the U.S.A. Then I present estimates of time-series demand functions. Next, I discuss how economists have modified their traditional model of consumer behaviour to incorporate the addictive aspects of illegal substances. I conclude with implications for tax policy and for the lively and contentious debate concerning the legalization of marijuana, cocaine, and heroin. PMID- 17867234 TI - Demand for illicit drugs among pregnant women. AB - We use postpartum survey data linked to medical records and city-level drug prices to estimate the demand for illicit drugs among pregnant women. We find that a $10 increase in the retail price of a gram of pure cocaine decreases illicit drug use by 12-15%. The estimated price effects for heroin are lower than for cocaine and are less robust across alternative model specifications. This study provides the first estimates of the effects of drug prices on prenatal drug use and yields important information about the potential of drug enforcement as a tool for reducing illicit drug use among pregnant women. PMID- 17867235 TI - The effect of alcohol consumption on the earnings of older workers. AB - This study analyses the effects of alcohol consumption on the labour market outcomes of older individuals. The data set used consists of five waves of the Health and Retirement Study. The results from models with a limited number of covariates indicate that there is a wage and earnings premium associated with alcohol use. This premium progressively diminishes as more individual-level controls are added to the standard earnings function. The data set is longitudinal which allows for estimation of individual-fixed-effects specifications. These results indicate that alcohol use does not have a positive effect on earnings and wages. PMID- 17867236 TI - Drugs and juvenile crime: evidence from a panel of siblings and twins. AB - Using data from the U.S. National Longitudinal Study of Adolescent Health, this chapter investigates the impact of individual drug use on robbery, burglary, theft, and damaging property for juveniles. Using a variety of fixed-effects models that exploit variations over time and between siblings and twins, the results indicate that drug use has a significant impact on the propensity to commit crime. We find that the median impact of cocaine use on the propensity to commit various types of crimes is 11 percentage points. The impact of using inhalants or other drugs is an increase in the propensity to commit crime by 7 percentage points, respectively. PMID- 17867237 TI - Antidepressants and the suicide rate: is there really a connection? AB - Recent research claims that the major part of the observed reduction in suicide rates during the 1990s can be explained by the increase in the prescription of antidepressants. However, this conclusion is based on research that only looks at raw correlations; confounding effects from other variables are not controlled for. Using a rich Swedish data set, we reinvestigate the issue. After controlling for other covariates, observed as well as unobserved, that might affect the suicide rate, we find, overall, no statistically significant effects from antidepressants on the suicide rate; when we do get significant effects, they are positive for young persons. Regarding the latter result, more research is needed before any firm policy conclusion can be made. PMID- 17867238 TI - Choice, social interaction and addiction: the social roots of addictive preferences. AB - It is argued that addicts, as people in general, are forward-looking and that they try to make the best of what they have got. However, this does not imply that they are fully rational. Cognitive defects, instabilities in preferences, and irrationalities in the form of wishful thinking and dynamical inconsistency play an important role in addictive behaviours. These "imperfections" in people's rationality may not have very large consequences in the case of ordinary goods, but their effect can be dramatic in relation to addictive goods. In the first part of the paper, the rational addiction theory and the empirical evidence that have been presented in support of the theory is reviewed. Regarding the conventional tests of the theory by econometric methods, it is argued that the tests are misguided, both theoretically and methodologically. Furthermore, it is claimed that the definition of addiction implicit in the rational addiction theory is unrealistic, and that the theory makes unrealistic assumptions about human nature. Some empirical evidence for these claims is reviewed. It is concluded that although the theory has its virtues, it faces serious problems and must be rejected in its original form. Secondly, the socio-cultural embeddedness of addictive behaviours, and the social roots of individual preferences, are discussed. These issues are more or less ignored in rational addiction theory. It is argued that we cannot expect to obtain a proper understanding of many addictive phenomena, unless they are seen in their proper socio-cultural context. PMID- 17867239 TI - The spread of drug use: epidemic models or social interaction? AB - This chapter argues that models trying to explain the spread of drug use should not be based on standard epidemiological models developed to describe the spread of infectious diseases. The main weaknesses of the standard model are the lack of attention to micro-foundations and the inappropriateness of several of its assumptions in the context of drug use. An approach based on mechanisms and social interaction is argued to provide a promising alternative to the standard approach. To illustrate this, a model of the spread of drugs based on two mechanisms has been developed (observational learning and social stigma). Lastly, some of the difficulties in testing and deriving policy implications in these models are discussed. PMID- 17867240 TI - Structural estimation of peer effects in youth smoking. AB - This chapter outlines a new approach to measuring peer influence on the choice of a young person to smoke cigarettes. The methodology is based on estimating an equilibrium discrete choice model in which the relative benefit to smoking is increasing in the fraction of peers who smoke. In contrast to much of the literature, this structural model allows for positive correlation in observable and unobservable characteristics between peers. The structural approach has been applied to estimating close friend peer effects in Canada, California, and the U.S.A. in general. In all three settings, I find that close friend smoking is substantially less influential than is generally found by previous studies. PMID- 17867241 TI - Trends in wine consumption in Norway: is diffusion theory applicable? AB - The study aimed at assessing whether diffusion theory may be applicable to explain the increasing trends in consumption of table wine in Norway over a four decade period. Data comprised a series of eight cross-sectional surveys from 1962 to 1999 in national samples of adults. The results indicated that diffusion theory might in part be applicable to explain the trends in wine consumption in Norway. Thus, early adopters were characterized by high social status and being more "cosmopolite". Yet, the typical S-shaped curve for adoption rate was not found, nor the expected association between wine consumption and social network. PMID- 17867242 TI - An investigation of the effects of alcohol policies on youth STDs. AB - The purpose of this chapter is to examine the role of alcohol policies in reducing the incidence of sexually transmitted diseases (STDs) among youth. Previous research has shown that risky sexual practices (e.g., unprotected sex and multiple partners) that increase the risk of contracting an STD are highly correlated with alcohol use. If alcohol is a cause of risky sexual behaviour, then policies that reduce the consumption of alcohol may also reduce the incidence of STDs. In this chapter, we examine the relationship between alcohol policies (e.g., beer taxes and statutes pertaining to alcohol sales and drunk driving) and rates of gonorrhea and acquired immune deficiency syndrome (AIDS) among teenagers and young adults. Results indicate that higher beer taxes are associated with lower rates of gonorrhea for males and are suggestive of lower AIDS rates. Strict drunk driving policies in the form of zero tolerance laws may also lower the gonorrhea rate among males under the legal drinking age. PMID- 17867243 TI - Can we model the impact of increased drug treatment expenditure on the U.K. drug market? AB - This chapter introduces a simulation model to estimate the social costs of problem drug misusers in England and Wales, and how policies to increase the number of drug users in treatment may impact on both social costs and government expenditure. Consequences are divided into five domains--health, crime, social care, work, and driving. Social costs are estimated to be between pound 12 and pound 12.3 billion, and the total cost of government expenditure is around pound 3.5 billion. Increases in the numbers in treatment, are estimated to reduce social costs across a 5-year period by between pound 3.0 and pound 4.4 billion. PMID- 17867244 TI - Tobacco control policies and youth smoking: evidence from a new era. AB - This chapter examines the impact of cigarette prices, taxes, and tobacco control policies on youth and young adult smoking propensity and intensity, in the U.S. during the years 1997-2001, a period characterized by significant changes in cigarette prices and tobacco control policies. Employing a fixed effects technique, we find a strong negative impact of cigarette prices and taxes on youth and young adult smoking prevalence and conditional demand. Moreover, we find purchase, use, and possession laws to be inversely related to youth and young adult smoking prevalence. PMID- 17867245 TI - The fires are not out yet: higher taxes and young adult smoking. PMID- 17867246 TI - Coupons and advertising in markets for addictive goods: do cigarette manufacturers react to known future tax increases? AB - We develop and test a pricing model for a monopolist that sells an addictive good. The model illustrates the conditions under which a monopolist lowers the price he charges youth when a future tax is imposed. Using household survey data, we investigate whether individuals use "cents-off" coupons in a way consistent with the price discrimination implied by the model. We find evidence that all smokers, not just the young, are more likely to use coupons prior to a tax increase if they are exposed to more advertising. With our data we cannot test whether cigarette manufacturers selectively offer youth price discounts in other ways. PMID- 17867247 TI - Symbolism and rationality in the politics of psychoactive substances. AB - Psychoactive substances take on many symbolic meanings, and thus the politics of psychoactive substances has featured symbolic elements, or value-based rationality, alongside and often dominating instrumental rationality. Drawing particularly on the work of Joseph Gusfield and Nordic scholars, the chapter considers the symbolic dimension in the politics of substance use, even in Nordic countries celebrated for their societal commitment to knowledge-based policymaking, and its effects on the interplay of science and policy. PMID- 17867248 TI - What does it mean to decriminalize marijuana? A cross-national empirical examination. AB - Although frequently discussed as a singular policy, there is tremendous variation in the laws and regulations surrounding so-called decriminalization policies adopted by Western countries, with many jurisdictions adopting depenalization policies rather than policies that actually change the criminal status of cannabis possession offences. This paper provides a discussion of the liberalization policies being adopted in Western countries, highlighting distinct elements about particular policies that are important for proper analysis and interpretation of the policies. It then discusses some of the environmental factors that also shape these policies, and hence influence their potential impact, using data from the U.S.A. as a particular example. The results clearly show that researchers should be careful conducting intra- or international comparisons of policies because important aspects of these policies are frequently ignored. PMID- 17867249 TI - Economic perspectives on injecting drug use. AB - Injecting drug use (IDU) has traditionally been seen as a law enforcement problem and a stain on society. With the emergence of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), however, the discourse on IDU has widened to include crucial public health and human rights concerns. Economic analysis, too, has much to contribute to the policy debate. By examining the costs and benefits of drug use from the perspective of injecting drug users, economic analysis can shed light on the problem of IDU and the transmission of HIV among users. This chapter also presents new results on the economic analysis of needle exchange programmes. PMID- 17867250 TI - Models pertaining to how drug policy should vary over the course of a drug epidemic. AB - The goals of this chapter are three-fold: (1) to outline some broad empirical regularities concerning how drug problems evolve over time, (2) to sketch some plausible mechanisms for ways in which aspects of that variation might be endogenous, and (3) to review two classes of dynamic models of drug use that have implications for how policy should vary over a drug epidemic. PMID- 17867251 TI - Economic evaluation of relapse prevention for substance users: treatment settings and health care policy. AB - Evaluating the prevention, intervention, and treatment programme is critical to understanding the decision-making behaviour of substance abusers. The study interweaves behavioural health economics with the extended PRECEDE-PROCEED Model and examines the effectiveness of treatment settings for substance users in New Jersey Drug and Alcohol Abuse Treatment (13,775 samples). The study also identifies the factors that are associated with substance users' recurrence to the treatment centre. The results concluded that educational attainment, counselling services from health care providers, mental agency services, and detoxification treatments have a significant impact on preventing relapse behaviour. PMID- 17867252 TI - Antimicrobial resistance in Neisseria gonorrhoeae and limited treatment options. PMID- 17867253 TI - Blindness in children at the Ida Rieu school for the blind and deaf. AB - OBJECTIVE: To identify the causes of blindness at the Ida Rieu school for the blind and deaf, Karachi, Pakistan. METHODS: A cross sectional study was conducted at the Ida Rieu School for the blind and deaf. The data collected from medical record of students was entered into the WHO/PBL eye examination form for children with blindness and low vision. RESULTS: Records of 144 pupils aged between 4-30 years were reviewed, including 67% males and 33% females. One third (31%) children had visual impairment (< 6/18-6/60) and 69% were blind (< 3/60-NPL). The commonest anatomical site was retina (41%) and whole globe (20%). The etiology was unknown in 49% cases. In 33% of cases, the data suggested hereditary cause as the etiology, 40% of cases were preventable and 13% treatable. CONCLUSION: Avoidable causes of blindness were seenin 53% of children, 58% of which were preventable and 19 were treatable. PMID- 17867254 TI - Association of Helicobacter pylori with carcinoma of stomach. AB - OBJECTIVE: To note the association of Helicobacter pylori in patients having carcinoma of stomach. METHODS: A descriptive study was carried out at the Department of Histopathology, Ziauddin Medical University, Karachi from April 1992 to May 1998. Histological evaluation of 50 cases of carcinoma of stomach was compared with 50 cases each of chronic gastritis and histological normal gastric mucosa. Only those cases of carcinoma of stomach were included that contained sufficient non-neoplastic mucosa in addition to tumour tissue. Three glass slides with serial sections of each case of carcinoma of stomach, chronic gastritis and normal gastric mucosa were freshly cut and stained with H&E, PAS and Giemsa stains. All slides were examined by light microscopy. RESULTS: Helicobacter pylori were identified in 35 cases (70%) of carcinoma of stomach, in 42 cases (84%) of chronic gastritis, and in 12 cases (24%) of normal gastric mucosa. The presence of H. pylori in cases of carcinoma of stomach and chronic gastritis was highly significant (P < 0.001) as compared to normal gastric mucosa. Chronic gastritis was observed in the non-neoplastic mucosa in 48 cases (96%) with carcinoma of stomach. Of 50 cases with carcinoma of the stomach, intestinal type of carcinoma was found in 30 cases (70%), and diffuse type in 15 cases (30%). No significant difference was noted in the prevalence of H. pylori between intestinal type (69%) and diffuse type (71%) gastric carcinoma. Significant Helicobacter pylori associated chronic gastritis was observed in intestinal type (94%) and diffuse type (100%) of gastric carcinoma. The prevalence of H. pylori was insignificant in the presence or absence of mucosal atrophy and intestinal metaplasia in both types of gastric carcinoma. CONCLUSION: A significant number of H. pylori were found in patients of carcinoma of stomach. Both intestinal and diffuse types of gastric carcinoma showed strong association with H. pylori. Chronic gastritis appears to be the background lesion while atrophy and intestinal metaplasia indicate long term infection. PMID- 17867255 TI - Multiple myeloma: a ten year study of survival and therapy in a developing nation. AB - OBJECTIVE: To analyze the survival related to therapeutic modalities and haematological indices at presentation with outcome performed on records of all multiple myeloma (MM) patients'. METHODS: A prospective study was conducted in the University of Benin Teaching Hospital, Nigeria from 1993 to 2003. Thirty patients were identified with diagnosis confirmed on the basis of atypical plasmacytosis (=30% in the bone marrow), monoclonal component in the serum or urine and radiological evidence of the typical skeletal lytic lesions. RESULTS: Males (n = 20) outnumbered the females (n = 10), with a median age of 54 years. The mean duration of survival of all patients was 7 months (median 3 months; P < 0.0001) with only 13.3% of the patients surviving at two years. The mean duration of survival of 10 patients on either therapy of vincristine, adriamycin, dexamethasone (VAD) or 8 patients on melphalan, prednisolone (MP) was 3 months, significantly shorter than 21 months for the 5 patients on a combination of both forms of therapy at different times (COMB) (P = 0.0067). The Kaplan-Meier estimates of survival showed survival probability was least in those without definitive therapy (NONE) as expected. CONCLUSION: Late presentation and inadequate treatment from poor compliance with therapy in a setting of poverty and ignorance are suggested as factors contributing to the poor survival of the patients studied PMID- 17867256 TI - Poor glycaemic control is the major factor associated with increased frequency of gastrointestinal symptoms in patients with diabetes mellitus. AB - OBJECTIVE: To compare the GI symptoms in diabetic patients with controls and its relationship with the complications, duration of diabetes and glycaemic control. METHODS: Consecutive patients were prospectively enrolled in to two groups. Group I (diabetic patients) and Group II (non-diabetic, Controls). Patient's characteristics, demographic profiles and GI symptoms were evaluated on a questionnaire. Groups were compared for differences in various GI symptoms. Group I was further analyzed for the relationship between GI symptoms with complications, duration of diabetes and glycaemic control. RESULTS: A total of 514 patients were enrolled 250 were diabetics (group I) and 264 were non diabetics (group II). Mean age was 51.8 +/- 10.6 years and 50.2 +/- 9.2 years in groups i and ii respectively. All GI symptoms; heartburn, dyspepsia, bowel related abdominal pain, diarrhea, constipation, and faecal incontinence were significantly more in diabetics than controls (P < .5). The presence of diabetic neuropathy, retinopathy and HbAlc of > 7 were significantly (P < .5) related to GI symptoms. Duration of diabetes (>10 years) was not found significantly linked to GI symptoms. CONCLUSIONS: GI symptoms in diabetics were more frequent then control subjects and were significantly associated with poor glycaemic control, neuropathy and retinopathy but not with duration of diabetes. Number of GI symptoms increases with the severity of poor glycaemic control in diabetic patients PMID- 17867257 TI - Adverse effects of diclofenac sodium on renal parenchyma of adult albino rats. AB - OBJECTIVE: To see the toxic effects of NSAID on kidney tissue of albino rats. METHODS: For this experimental study, 16 albino rats were taken. They were divided into two groups; A and B. The animals in group-A were given Normal Saline. Group-B received Diclofenac Sodium 2 mg/kg/day by feeding tube for 14 days. On day-15 all animals were sacrificed. Kidneys were removed, fixed, embedded in paraffin, section cut at 4 microm thick and stained with H&E, PAS, and silver methenamine. Renal histology was done under light microscope to see the renal tubular diameter, count and cellular detail. RESULTS: The result of present study revealed that diclofenac sodium in single daily dose of 2 mg/kg for a period of two weeks effectively produced destruction of proximal and distal convoluted tubules in adult albino rats showing the dilatation of tubule and flattening of tubular epithelium, disruption of brush border in proximal tubule and thickening of basement membrane around proximal and distal tubular epithelium. CONCLUSION: Diclofenac sodium induced nephrotoxicity causes the destruction of proximal and distal convoluted tubules showing the dilatation of tubule and flattening of its epithelium in albino rats. PMID- 17867258 TI - The correlation between ultrasonic manual and automatic measurements of foetal head and abdominal circumferences. AB - OBJECTIVE: To assess the correlation between ultrasonic manual and automatic ellipsoid measurements of foetal head and abdominal circumferences. METHODS: This comparative cross-sectional study was conducted at the Ultrasound Clinic, Karachi, from January to July 2004. Seventy two normal pregnant women with gestational ages between 14 to 38 weeks were included. Foetal head and abdominal circumferences were measured by manual method using traditional formulae and by automatic ellipsoid mode incorporated into the real-time ultrasound machines (EcoCee and Power Vision, Toshiba, Japan) using convex probes of 3 and 4.2 MHz frequency. Three readings of each parameter i.e. head circumference (HC) and abdominal circumference (AC) were taken by both methods. Mean values were calculated and compared using paired sample 't' test to assess the correlation between ultrasonic manual and automatic ellipsoid measurements. RESULTS: The mean HC measured through manual method was found to be 20.11 +/- 7.04 cm and was significantly different from that of 19.46 +/- 6.82 cm measured through ellipsoid automatic technique. There was, however, a perfect positive correlation (r = 0.999) between these measurements. In case of AC, there was no statistical difference between the mean values obtained by the manual technique and those measured automatically (16.79 +/- 6.24 vs. 16.74 +/- 6.11; p < 0.44), correlation between these measurements (r = 0.997) was also significantly positive. CONCLUSION: Correlation was found between the mean measurements of the foetal HC and AC by the manual and the automatic method of calculation; and even stronger for the latter. The automatic mode of measurement is a more rapid method than the manual calculation, and its use may be encouraged. PMID- 17867259 TI - Laparoscopic nephrectomy: technique and outcome. AB - OBJECTIVE: To review case series of retroperitoneal laparoscopic nephrectomies. METHODS: Between May 2003 and May 2006, 60 laparoscopic nephrectomies were performed by a single surgeon. Laparoscopic route for nephrectomy was retroperitoneal in 50 cases and transperitoneal in 10 cases. RESULTS: The patients included 37 males and 23 females. The mean age was 18.5 +/- 16.6 years and ranged from 2 years to 60 years. Right sided nephrectomy was performed in 31 cases while left kidney was removed in 29 cases. The indications for nephrectomy were stones (n = 29), dysplasia (n = 11), chronic pyelonephritis (n = 8), pelvi ureteric junction obstruction (n = 4), tuberculosis (n = 3), vesicoureteric reflux (n = 3) and ureterocele(n = 2). Mean operating time for laparoscopic nephrectomy alone was 140 +/- 51.1 min (range 25-300 minutes). In our series, 19 additional surgical procedures were performed under the same general anaesthesia. The mean hospital stay for all patients was 3.1 +/- 2.39 days; however the mean hospital stay for those patients who underwent laparoscopic nephrectomy without any additional procedure is 2.2 +/- 0.92 days (1.5-4 days). The mean size of kidney removed was 7.4 +/- 3.13 cm (4.6-15.9 cm). Complications were seen in 2 patients (3%); one developed wound infection and the other was found to have a haematoma for which the wound was re-explored. Conversion to open nephrectomy was required in 7 patients (11.6%) due to bleeding from renal pedicle (n = 4), poor vision secondary to pus spillage from pyonephrotic kidney (n = 2) and failure to progress due to indwelling percutaneous nephrostomy. There was no mortality and none of the patients had prolonged ileus. Blood transfusion was not required in any case. There was no bowel injury or port site herniation. CONCLUSION: Laparoscopic nephrectomy is a feasible and safe technique. The length of hospital stay and convalescence is short and hence rapid return to normal activity is expected. PMID- 17867260 TI - Aspiration of thrombus in ST segment elevation myocardial infarction. AB - OBJECTIVE: To evaluate the impact of Export Aspiration Catheter with restoration of ECG changes, arterial flow and myocardial perfusion in patients with ST segment elevation Myocardial Infarction undergoing Percutaneous Coronary Intervention (PCI). METHODS: A total of 40 consecutive patients with ST Segment Elevation Myocardial Infarction (STEMI) were selected. They underwent treatment according to the surgeon's discretion to either standard PCI or PCI with thrombus aspiration Catheter. Primary end points of the study were ST Segment resolution (STR) > 70% and myocardial blush grade (MBG) > 2. RESULTS: The base line clinical and procedural characteristics were same for both the groups. In the post intervention comparison the thrombus aspiration group was found to have significantly better outcomes as compared to the standard PCI group with regards to TIMI flow grade (p = 0.009) and myocardial blush grade (p = 0.001). Considering the criteria for MBG and STR together, the thrombus aspiration was found to have significantly better outcome than the standard PCI group (p = 0.017). CONCLUSION: This non-randomized study shows that Export Aspiration Catheter group with STEMI undergoing primary PCI is feasible and results in better angiographic ECG and myocardial perfusion rates compared with standard PCI. Role of export catheter in rescue PCI and thrombus Sapheneous Venous Graft (SVG) as primary PCI is questionable and needs larger randomized studies to prove its efficacy. PMID- 17867261 TI - Prevalence and factors associated with postpartum vaginal infection in the Khyber Agency federally administered tribal areas, Pakistan. AB - OBJECTIVE: To estimate the prevalence and to identify the factors associated with vaginal infection among the married women between the ages of 15-49 years residing in the Khyber Agency (FATA), Pakistan. METHODS: A cross-sectional study was conducted in the month of July 2005 on 1084 mothers by using random sampling strategy in Khyber Agency Pakistan by trained nurses. The descriptive and multivariate statistics were computed. RESULTS: The multivariate analysis showed that the associated factors with vaginal infection were the use of unhygienic material to soak up the lochia [aOR = 3.45, 95% CI (1.36, 8.75)], bathing after 40 days [aOR = 2.10, 95% CI (1.55, 3.14)], and women who did not receive antenatal care [OR = 3.87, 95% CI (1.93, 7.75)]. Also women who did not have medical facilities available [OR = 2.45, 95% CI (1.23, 5.06)] reported of vaginal infection. CONCLUSIONS: This study concluded that there is considerable need for health education among women and the entire community for the maintenance of hygiene, safe delivery through medical personnel and improvement in the mobility of mothers and female education. PMID- 17867262 TI - Clinical features and management of Merkel cell carcinoma. AB - Merkel cell carcinoma (MCC) is an aggressive dermal tumour of neuroendocrine origin. MCC is a rare tumour and all information pertaining to its behaviour, therapy and prognosis is based on retrospective reports. The two potentially curative treatment modalities are surgery and radiotherapy. It is a rare, highly malignant primary skin tumour, originally called "trabecular carcinoma" of the skin. MCC poses a challenge to the clinician because of its rarity and poor prognosis. The optimal therapy is customised and tailored for each individual patient with the appropriate use of operative resection and radiation therapy. This review covers reports from several authors regarding the rationale of using postoperative radiotherapy to the primary tumour and regional lymphatics. Although MCC is classified as a type of neuroendocrine carcinoma, it is less likely to be controlled by systemic chemotherapy. Management of primary lesion with clinically localised disease is wide excision with margin of at least 2 cm whenever possible. MCC is a radiosensitive tumour, adjuvant radiotherapy has been advocated in order to control local as well as regional disease. Radiation induced toxicity should be considered and discussed with the patient. Adjuvant radiation to the nodal bed after complete lymphadenectomy in patients with metastatic disease is generally not recommended. PMID- 17867263 TI - Adequacy of postoperative pain relief after discharge. AB - Day care surgery has shown a remarkable development over the last two decades, comprising approximately 60-70% of all surgical procedures. Therefore major proportions of surgical patients are recovering at home and have little or no assessment of the adequacy of their pain relief. The aim of our audit was to compare suggested postoperative pain indicators with targets for best practice. This audit was done at the Aga Khan University Hospital day care unit for a period of three months. On the day of surgery patients having the contact numbers were informed about the telephone call 24 hrs after the surgery inquiring about their pain relief. Patients were shown and explained the visual analogue score from 0 to 10. The data was collected by one of the investigators on the day of surgery. We could assess 63.3% of day care patients. All patients were discharged with analgesia. Only three percent reported severe pain after 24 hrs which is according to the proposed standard for best practice that is < 5%. Sixty percent of patients had mild or no pain which is less than the proposed standard (> 85%) and 84.2% were satisfied which is almost borderline (> 85%) according to the standard of best practice. PMID- 17867264 TI - Clear cell carcinoma of ovary with associated mucinous cystadenoma and endometriosis. AB - A 45 year old woman presented with right sided ovarian mass with multiple omental deposits and liver metastases. The right ovary was enlarged and showed a partly cystic partly solid cut surface. Histological picture showed clear cell carcinoma with areas of mucinous cystadenoma and endometriosis. Clear cell carcinoma is known to be associated with endometriosis. To the best of author's knowledge, it's association with mucinous cystadenoma has been described only once in the literature, where clear cell carcinoma was shown to be associated with mucinous cystadenoma without any evidence of endometriosis. PMID- 17867265 TI - Gallstone ileus and bowel perforation: a rare complication of therapeutic ERCP. AB - Gallstone ileus is rare following an Endoscopic Retrograde Cholangio Pancreaticography (ERCP). We present a case where gallstones caused ileus and perforation of small bowel after a therapeutic ERCP. There was no previous history of instrumentation of the papilla or a cholecystoenteric fistula. This case points out a serious morbidity of therapeutic ERCP for large common bile duct stones. PMID- 17867266 TI - Acute stroke secondary to internal carotid artery pseudoaneurysm: MRI findings and treatment with endovascular coiling. AB - Internal carotid artery pseudoaneurysms are uncommon. We report a young man with history of trivial trauma who presented with middle cerebral artery stroke. Head CT scan revealed a right parapharyngeal mass. MRI confirmed the diagnosis of internal carotid pseudoaneurysm. Cerebral angiogram showed dissection of internal carotid artery with a large pseudoaneurysm and almost complete occlusion of vessel distal to aneurysm. Vessel was obliterated by fibercoiling and gluing by endovascular technique to diminish risk of further embolization. MRI characteristics of carotid pseudoaneurysms and role of endovascular treatment are discussed. PMID- 17867267 TI - Medical doctors in media: is this a viable alternate career option? PMID- 17867268 TI - Physician-pharmaceutical interaction: training the doctors of tomorrow. PMID- 17867269 TI - Inflammatory biomarkers of stroke. PMID- 17867270 TI - Thyroid disorders in Khulna district: a community based study. AB - This study reports the prevalence of thyroid diseases and their relationship to autoimmunity in a population of Khulna district where goitre is not endemic. A survey was performed among citizens of a union of Khulna district. The study population consisted of a random sample of the students of primary schools, secondary schools and people of nearby areas. History taking, neck examination for goitre and blood examination for thyroid hormones was done from each subject. Blood sample was measured for thyroid hormones and thyroid microsomal antibody (TMAb) using radioimmunoassay method. Of the total 925 individual studied, 527 was female and 398 was male with age ranges from 2-62 years (mean 19.86 +/- 13.62 years). The overall occurrence of thyroid disease was estimated to be 20.43%. The spectrum of thyroid disorders showed highest incidence of diffuse goitre (7.35%), followed by sub-clinical hypothyroidism (6.59%), hypothyroidism (4.97%), hyperthyroidism (0.86%) and sub-clinical hyperthyroidism (0.65%). The incidence of thyroid disorders was observed to be highest in the 11-45 years age group (79.89%). Female outnumbered male, the ratio being 2.5:1 with preponderance of female subjects in all disease groups. The prevalence of all goitre was 10.49%. TMAb estimation was performed in 318 samples, of them 48 cases (15.09%) was found to be autoimmune thyroid disease. Of the total sub-clinical and overt hypothyroidism, the incidence of autoimmune thyroid disease was 29.29% and non goitrous thyroid dysfunction was more common than goitrous one. Three of 38 (7.89%) euthyroid goitrous subjects showed positive antibody. Interestingly, 16 of 181 (8.84%) individual had a positive antibody, which was considered normal by neck examination. Goitre prevalence of 10.49% in this study indicates the region to be a mild iodine deficient area. Chronic autoimmune disease is likely to be one of the etiological factors for thyroid disorders in this southern zone. PMID- 17867271 TI - Colonic secretion studied in vitro in rats fed polyunsaturated fatty acids. AB - Recent studies primarily in man have shown that cod fish oil rich in polyunsaturated fatty acids (PUFA) are beneficial to certain inflammatory diseases such as ulcerative colitis. This study was undertaken to observe any change in intestinal secretion where the tissues have been treated with cod fish and sunflower oils. Male Sprague Dawley rats weighing 200 gms were fed omega-3 fatty acids for 50 days. Changes in colonic secretion (fed with PUFA) were studied in-vitro in an Ussing chamber. Rat colon which were not fed with PUFA served as controls. Basal intestinal short circuit in PUFA group were comparable with control group in stripped rat colon. The results showed significant high short circuit current in cod fish oil and sunflower oil treated tissues. When stripped colonic tissues (fed with PUFA) were stimulated by EC50 of carbachol, bradykinin and prostaglandin; there was no significant changes in Short circuit current. PGE2 and LTB4 levels were measured in rat colon fed with PUFA by using radioimmunoassay. Biochemical changes in PGE2 and LTB4 levels showed LTB4 were significantly raised in both cod fish oil group and sunflower oil group. This study reveals that intestinal permeability increases in the rat colon (fed with PUFA) as indicated by high short circuit current. The high levels of leukotriene in colonic tissues also explains the high basal short circuit current in the present study. PMID- 17867272 TI - Correlation between microalbuminuria and angiographic severity of coronary artery disease. AB - Microalbuminuria has emerged as an important risk factor of considerable prognostic importance for cardiovascular events. Little is known about its impact on the angiographic profile among coronary artery disease patients. The primary aim of the study was to investigate the relationship of microalbuminuria and angiographic severity of coronary artery disease. This was a cross-sectional study conducted in NICVD, a tertiary-care cardiac center in Dhaka, Bangladesh. For this purpose, 72 patients aged 25 to 70 years, who underwent elective coronary angiogram were studied. Urinary albumin to creatinine ratio was used as a measure of microalbuminuria. Angiographic severity of coronary artery disease was measured by number of major vessels involved (vessel score), stenosis score, extent score and number of type B and C lesions. All parameters of angiographic severity were significantly higher in microalbuminuric patients. Spearman's rank correlation coefficient showed significant positive correlation between albumin to creatinine ratio and different parameters of angiographic severity. In multivariate logistic regression analysis odds ratio of having triple vessel coronary artery disease in microalbuminuric patients was 5.6 (95% CI, 1.4 - 22). Microalbuminuria was found to correlate positively and independently with angiographic severity of coronary artery disease. PMID- 17867273 TI - Zinc supplement on tissue arsenic concentration in rats. AB - To examine the effect of zinc in the removal of accumulated arsenic from different tissues (liver, kidneys, spleen and lungs), rats were initially allowed to drink high concentration (400 microg/kg/day) of arsenic for two months followed by a period of cessation (one month). Administration of zinc (2 mg/kg/day) during the third month in arsenic-treated and non-treated groups were compared. In arsenic-treated rats, the mean (+/- SD) amounts of total arsenic in liver, kidneys, spleen and lungs were 12.3 +/- 0.7, 20.5 +/- 1.0, 31.4 +/- 1.0 and 25.6 +/- 1.1 microg/g of tissues respectively. Administration of zinc to arsenic-treated rats reduced the arsenic concentrations of those tissues to 7.8, 10.7, 23.0 and 14.0 microg/g of tissues. This in vivo study suggests that zinc removes the accumulated arsenic from different tissues significantly (p < 0.001). PMID- 17867274 TI - Critical evaluation of research articles in relation to informed consent. AB - The concept of research bioethics arose and developed over the last three decades mainly in response to moral crisis created by rapidly advancing medical science and technology. Accordingly, reinterpretation of some fundamental principles of ethics is needed. At the heart of the ethical principle of respect for person, lies the informed consent process. Nuremberg Code, Helsinki Declaration of World Medical Association (WMA), Council for International Organizations of Medical Sciences (CIOMS) Guidelines etc. demonstrated the importance of informed consent in biomedical research involving human subjects. This article was planned to evaluate the reflection of informed consent in the published research articles. Fifty-two articles published in national and international journals were studied among which informed consent was found to be taken only in 21(40.4%) occasions and the same was not taken in 31(59.6%) occasions. Study showed that out of 38 articles published in national journals, informed consent was taken from only in 12(31.6%) situations, while out of 14 articles published in international journals, informed consent was taken in 9(64.3%) situations. Out of 36 observational studies, informed consent (both written and verbal) was taken from only 27.8% cases, whereas out of 16 interventional experiments, informed consent was taken in 68.8% situations. PMID- 17867275 TI - Induction of peripheral tolerance by local delivery of dendritic cell progenitors to cardiac allografts in a murine heterotopic heart transplantation model. AB - OBJECTIVE: Systemic injection of donor-derived dendritic cell (DC) progenitors is reported to prolong cardiac allograft survival in nonimmunosuppressed hosts. Our purpose was to identify whether tolerance limited to the cardiac allograft is inducible by direct delivery of DCs to the myocardium, thus diminishing the potential for systemic side effects. METHODS: The donors were 8- to 12-week-old male B10/ H2b mice. The recipients were 8- to 12-week-old male C3H/H2k mice. For DC culture, DCs were propagated from donor bone marrow with granulocytic/macrophage colony stimulating factor (GM-CSF) (GM-CSF DCs) and/or interleukin-4 (IL-4) (GM-CSF+IL-4 DCs). The phenotypes of DCs were analyzed by flow cytometry (FACScan). For DC assay, the JAM test (a DNA fragmentation assay), the mixed lymphocyte reaction (MLR), and flow cytometry were used. For local DC delivery to the myocardium, DCs were injected retrograde into the ascending aorta, and abdominal heterotopic vascularized heart transplantation was performed. Donor heart survival was recorded. RESULTS: JAM assays confirmed the induction of apoptosis in T cells by both DC preparations. Flow cytometry revealed that the GM-CSF DCs expressed diminished co-stimulatory molecules (B7-1 and B7-2) in comparison with the GM-CSF+IL-4 DCs. The mean survival time of cardiac allografts was 13.1 +/- 4.32 days for the controls, 35.0 +/- 25.7 days for DCs cultured with GM-CSF, and 16.9 +/- 7.30 days for DCs cultured with GM CSF+IL-4. CONCLUSION: Local delivery of GM-CSF DCs may induce graft tolerance and may prove to be more efficient than systemic delivery of DCs. Local delivery of GM-CSF+IL-4 DCs did not prolong cardiac graft survival, suggesting that the immune response elicited may be immunostimulatory. PMID- 17867277 TI - Left ventricular thrombus with a normal heart. AB - A 44-year-old man was found to have a left ventricular mass by transthoracic echocardiography. He had had multiple events of systemic embolization over the last few years. The heart was not dilated, and heart function was normal. Surgical excision was recommended to avoid further embolization. A transverse aortotomy was carried out under cardioplegic cardiac arrest with standard cardiopulmonary bypass. A transaortic video-assisted endoscopic procedure was performed. The mass was resected endoscopically without left ventriculotomy. Pathologically, the excised mass was an organized thrombus with a fibrous stalk connected to endocardium. We thus report a case of left ventricular thrombus with a normally functioning heart. PMID- 17867276 TI - Cardiopulmonary co-morbidity: a critical negative prognostic predictor for pulmonary resection following preoperative chemotherapy and/or radiation therapy in lung cancer patients. AB - OBJECTIVE: Preoperative therapy is an optional strategy for locally advanced lung cancer, although the indication for pulmonary resection is often marginal, when considering the survival benefit and perioperative risks. The aim of the present study was to identify prognostic predictors by assessing clinical factors including pre-thoracotomy co-morbidity. METHODS: This was a retrospective analysis of 54 patients who underwent complete resection after preoperative therapy was performed. RESULTS: The overall 5-year survival rate was 38%. In patients without cardiopulmonary co-morbidity the 5-year survival rate was 49%, whereas it was 0% for those who had associated cardiopulmonary co-morbidity (P = 0.004). When analyzing only those who died from lung cancer, the group without cardiopulmonary comorbidity showed a tendency for longer survival than those in the co-morbidity group (P = 0.092). The 5-year survival rate for patients- evaluated with a Charlson Co-morbidity Index (CCI)--with a CCI score of 0, was 45%, which tended to be better than that for those with a CCI score of 1-2 (P = 0.066). Furthermore, patients with a normal prethoracotomy level of carcinoembryonic antigen (CEA) had a 5-year survival rate of 44%, which was better than the 22% for patients with elevated CEA (P = 0.013). The 5-year survival rate for patients without lymph node metastasis was 52%, whereas it was 14% for those with residual node involvement (P = 0.002). Lymph node metastasis and cardiopulmonary co-morbidity were shown to be independent poor prognostic predictors by multivariate analysis. CONCLUSION: In addition to nodal status, preoperative cardiopulmonary co-morbidity should be noted when considering the operative indications following preoperative therapy for lung cancer patients. PMID- 17867278 TI - Concomitant surgery of a left atrial myxoma and a pulmonary carcinoma. AB - We report the first successful outcome of a patient undergoing concomitant surgery for a left atrial myxoma and a squamous cell carcinoma of the lung. Preoperative evaluations revealed lung cancer and a left atrial tumor of undetermined origin. An operation to excise both cardiac and pulmonary tumors was performed. The cardiac tumor was first resected with the aid of cardiopulmonary bypass. The histopathological diagnosis was myxoma. Resection of the left upper pulmonary lobe and mediastinal lymph nodes followed. The postoperative course was uneventful, and the patient is well without evidence of recurrence 7 years after the operation. PMID- 17867279 TI - Chronic diaphragmatic hernia. AB - Chronic diaphragmatic hernia is a rare entity and requires surgical intervention when it is diagnosed. We report three patients with chronic diaphragmatic hernia that followed a diagnosis of diaphragmatic abnormality with no previous chest injury. Operative findings suggested a diaphragmatic defect in a congenitally weak area. All patients were satisfied with the resolution of their preoperative discomfort and their improved respiratory function after repair using Marlex mesh sheets via thoracotomy and laparotomy. Chronic diaphragmatic hernia should be considered even in patients who had no previous chest injury. PMID- 17867280 TI - Use of the Bentall method for replacement of an aortic Starr-Edwards ball valve prosthesis implanted 32 years previously. AB - We report the case of a 54-year-old woman who, 32 years previously, had undergone replacement of the ascending aorta by the inclusion method with a Starr-Edwards ball valve prosthesis and recently underwent aortic root re-reconstruction by the Bentall method. Routine chest radiography revealed dilatation of the mediastinum, and computed tomography revealed an aneurysm of the ascending aorta. At reoperation, although the cloth covering the cage of the Starr-Edwards ball valve prosthesis appeared worn and some pannus formation was seen, the Starr-Edwards ball valve was functioning normally. The aortic root was replaced with a composite graft that consisted of a 23-mm St. Jude bileaflet prosthesis and a 24 mm Hemashield gold graft. The patient was discharged from the hospital in good condition 25 days after surgery. PMID- 17867281 TI - Pulmonary histoplasmosis as an example of imported mycoses in Japan. AB - As travel increases, histoplasmosis as an imported mycosis that has the potential to increase abruptly in Japan. A 56-year-old Japanese man who had been in Bolivia for 2 years complained of a dry cough. Chest computed tomography revealed multiple lesions in the right and left lower lobes of his lung that were difficult to diagnose and differentiate from advanced lung cancer. We performed surgical resection for biopsy by video-assisted thoracoscopic surgery. An intraoperative histopathological examination suggested a diagnosis of tuberculoma, but Mycobacterium tuberculosis DNA was not detected in the tumor tissue. Further histopathological examination, however, strongly suggested a diagnosis of histoplasmosis because multiple small, round yeast foci were observed after Grocott staining. The serological test was positive for anti Histoplasma capsulatum and confirmed the diagnosis of pulmonary histoplasmosis. The postoperative course was uneventful, and fluconazole was administrated for 90 days after the operation. Concerning imported mycoses, physicians should be keep abreast of updated and detailed information. PMID- 17867282 TI - Regarding "floating thrombus in the ascending aorta". PMID- 17867283 TI - Regarding "radiation-induced valvular disease is the logical consequence of irradiation". PMID- 17867284 TI - [p130Cas, an ion channel-independent cytoskeletal mechano-sensor]. PMID- 17867285 TI - [Proton transport mechanism of bacteriorhodopsin: movement of a proton and water molecules inside of protein]. PMID- 17867286 TI - [Cytokinin biosynthesis and novel activating pathway]. PMID- 17867287 TI - [Notch signal diversifies olfactory receptor neurons and determines their axonal projection pattern in Drosophila melanogaster]. PMID- 17867288 TI - [Non-classical caspase functions and its regulatory mechanisms]. PMID- 17867289 TI - [Coupled dynamics of organelle biogenesis and vesicular transport during cell cycle]. PMID- 17867290 TI - [Quantum chemical study of the color tuning mechanism of photoreceptor proteins]. PMID- 17867291 TI - [Lipid database "LipidBank" and international collaboration]. PMID- 17867292 TI - [Present status for the rapidly expanding joint family of serine and cysteine proteases]. PMID- 17867293 TI - [Database center for life science in Japan]. PMID- 17867294 TI - [Picture in clinical Hematology. No 20]. PMID- 17867295 TI - [Continuous infusion of cyclosporine A and C3 monitoring in pediatric stem cell transplantation]. AB - We performed an intravenous cyclosporine (CsA) drip infusion method for 3 hours and C3 monitoring in pediatric hematopoietic stem cell transplantation and examined the internal change and monitoring method of CsA. A total of six cases comprised five cord blood transplantations and one related allogeneic bone marrow transplantation. We started CsA 1.5 mg/kg at the day before transplantation by intravenous drip infusion (twice a day) for three hours. We controlled the dose so that the optimal peak value of C3 reached 800-1000 ng/ml. We recognized the C3 peak occurred three hours after initiation of infusion, and the blood CsA concentration was restored to the baseline value (C0) to (C12) 12 hours after that. We found a strong correlation between the C3 value (r = 0.90), and AUC(0 12). Two patients had grade II acute graft-versus-host disease (GVHD), but one needed no treatment, and the other recovered with short-term dosage of prednisolone. Apart from these instances, no serious complication occurred. In pediatric hematopoietic stem cell transplantation, it seems that regulation of the appropriate blood CsA concentration is enabled by using C3 monitoring at around 3 hours after commencing the intravenous drip infusion method for CsA. PMID- 17867296 TI - [Clinical analysis of predictive factors for the response to antithymocyte globulin in patients with aplastic anemia]. AB - We report the results of a retrospective study of antithymocyte globulin (ATG) treatment in 17 adult patients with aplastic anemia (AA). We evaluated 24 ATG treatments which included re-treatment with ATG in patients who had not responded to the first ATG treatment or who had relapsed after the first remission. The median age was 66 years, and the median follow-up period was 52 months. The response and relapse rates of ATG treatment were 70.8% and 23.1%, respectively. The response rate of ATG re-treatment was 57.1%. Overall survival and event-free survival at 10 years were 66.7% and 50.7%, respectively. The shorter duration from diagnosis to ATG treatment, the higher reticulocyte count before ATG treatment, and being female independently correlated with the efficacy of ATG treatment. Two patients developed monosomy 7 clonal abnormality. These results suggest that ATG treatment can achieve a high response rate and long-term survival among patients with adult AA. However, we have to pay attention to the development of the clonal diseases. PMID- 17867297 TI - [Transient chromosomal abnormalities following autologous peripheral blood stem cell transplantation for acute myelogenous leukemia]. AB - Twenty-three patients with acute myelogenous leukemia (AML) have received autologous hematopoietic stem cell transplantation (autoHSCT) in our institute from 1997 to 2005. Among them, 3 patients relapsed, and the other 4 patients (17%) showed cytogenetic abnormalities after the autoHSCT. In these 4 patients with AML1/MTG8 or CBFbeta/MYH11 AML, RT-PCR findings using bone marrow cells were all negative when a cytogenetic abnormality was detected. Myelodysplasia was not detected in the bone marrow and no abnormal findings were seen in the peripheral blood. Cytogenetic abnormalities were detected 12-48 months after AutoHSCT, which disappeared in three patients and decreased in the remaining one patient with a median follow up time of 51 months (30-72 months) after their detection. We present our finding together with a review of the literature on post-autoHSCT cytogenetic abnormalities not related to relapse or secondary leukemia/myelodysplastic syndrome. PMID- 17867298 TI - [Benefits of mycophenolate mofetil for refractory graft-versus-host disease]. AB - We retrospectively evaluated the efficacy of mycophenolate mofetil (MMF) in the treatment of steroid-resistant acute and chronic graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation. Thirteen patients, ten men and three women, consisted of 5 cases of acute myelogenous leukemia, 2 of acute lymphoblastic leukemia, 2 of chronic myelogenous leukemia, 2 of lymphoblastic lymphoma, and 1 case each of adult T-cell leukemia and peripheral T-cell lymphoma. The transfusions consisted of 5 peripheral blood, 7 bone marrow and 1 cord blood from 3 mothers, 4 siblings and 6 unrelated donors with conditioning treatments, including 8 total-body irradiation-based regimens, and 2 busulfan plus cyclophosphamide and 2 reduced-intensity regimens. GVHD prophylaxis included FK506 plus methotrexate (MTX) and/or antithymocyte globulin for 9 patients, and cyclosporine and MTX for 4 patients. All patients were treated with second-line MMF for steroid-refractory acute and/or chronic GVHD, and 11 patients improved. The adverse events were tolerable except for one patient in whom grade 3 neutropenia forced discontinuation of treatment. No case of non-relapse mortality occurred. We consider that MMF is beneficial and well tolerated for treatment of steroid-refractory GVHD. PMID- 17867299 TI - [Transient leukemoid reaction of plasma cells in a patient with rheumatoid arthritis]. AB - A 69-year-old female with rheumatoid arthritis was admitted to our hospital with facial flushing and cervical lymphadenopathy on Jan, 2006. She had been treated with methotrexate (MTX), sulfasalazine (SSA) and prednisolone. The MTX and SSA were discontinued because of appetite loss just before admission. The patient's white blood cell count was 30100/microl with 32.5% of plasma cells, and 25.7% of plasma cells were observed in the bone marrow. Immunoelectrophoresis revealed polyclonal hypergammaglobulinemia on admission. Flow cytometry analysis revealed that the plasma cells in the bone marrow expressed CD38 and CD19 and did not express CD56. The lymphadenopathy and the increase of plasma cells in the peripheral blood and the bone marrow gradually decreased after the cessation of MTX and SSA. PMID- 17867300 TI - [Successful treatment with azathioprine for autoimmune thrombocytopenia developing after autologous peripheral blood stem cell transplantation]. AB - A 60-year-old man with acute promyelocytic leukemia in complete remission had minimal residual disease (MRD). After two courses of arsenic trioxide treatment, the MRD disappeared. In October 2005, he received an unmanipulated autologous peripheral blood stem cell transplantation (autoPBSCT). Hematologic recovery was prompt; however, after day 21 following the autoPBSCT, platelet counts decreased to below 10 x 10(9)/l. A bone marrow aspirate showed an increased number of immature megakaryocytes, and platelet-associated IgG was elevated to 48.5 ng/10(7) platelets. A diagnosis of autoimmune thrombocytopenia was made. The combination of oral prednisolone (40 mg/day) and bolus immunoglobulin infusion (400 mg/kg, for 5 consecutive days) was ineffective. He was given azathioprine (50 mg/day, orally), and 10 days after the initiation of the treatment, the platelet counts gradually increased and recovered to over 50 x 10(9)/l on day 168, and 100 x 10(9)/l on day 364. To the best of our knowledge, successful treatment of ITP following auto PBSCT with azathioprine has not been previously reported. PMID- 17867301 TI - [POEMS syndrome presenting with transient immunoglobulin isotype switching after successful treatment with autologous peripheral blood stem cell transplantation]. AB - A 60-year-old man was admitted with muscle weakness and numbness in the extremities. Based on the existence of monoclonal gammopathy of the IgG-lamda type, a slight increase of plasma cells in the bone marrow, and an elevated level of serum vascular endothelial growth factor (VEGF), the diagnosis of POEMS syndrome was made. After peripheral blood stem cell collection by etoposide and G CSF, the patient received high dose melphalan (200 mg/m2) therapy supported by autologous peripheral blood stem cell transplantation (autoPBSCT). After high dose chemotherapy with autoPBSCT, the serum VEGF level normalized and the monoclonal IgG-lamda, disappeared. The patient gradually recovered from a bedridden state and at the time of writing has no impairment in his activities of daily life. After the autoPBSCT, monoclonal IgG-kappa, protein was detected transiently in serum. The new monoclonal immunoglobulin was considered to be due to normal immune reconstitution after myeloablation rather than alteration of the abnormal plasma cell clone, similarly as oligoclonal immunoglobulins occur in multiple myeloma after autoPBSCT. AutoPBSCT with high-dose chemotherapy should be considered among the treatments of choice for POEMS syndrome. PMID- 17867302 TI - [Polyclonal B-cell lymphocytosis with hairy cell appearance: hairy B-cell lymphoproliferative disorder]. AB - A 72-year-old woman was referred to our hospital for evaluation of leukocytosis revealed by a medical examination. Her physical examination demonstrated no splenomegaly and no palpable lymph nodes. Her white cell count was 10,900/microl with atypical lymphocytosis (84.5%). Her hemoglobin concentration was 10.4 g/dl, and platelet count 151,000/microl. On peripheral blood smears, the atypical lymphocytes had a hairy cell-like appearance, and phase-contrast microscopic and transmission electron microscopic findings revealed the lymphocytes had many long surface microvilli. Flowcytometric analysis of peripheral blood lymphocytes identified expanded B-lymphocytes as having the IgG+, CD5- CD10- CD11c+ CD19+ CD20+ CD23- CD25- and CD103- cell surface phenotype. Serum electrophoresis disclosed polyclonal elevation of IgG and IgM (2620 mg/dl and 840 mg/dl, respectively). No light-chain restriction and a polyclonal VH gene rearrangement pattern indicated the polyclonal proliferation of B cells. The patient was a nonsmoker and had HLA-DR4, as in previous reports which have suggested an association between hairy B-cell lymphoproliferative disorder (HBLD) and HLA-DR4. No chromosome 3 abnormality was observed. These findings were consistent with the characteristics of HBLD, but differed in some respects from those of persistent polyclonal B-cell lymphocytosis (PPBL). Therefore, we diagnosed this patient as having HBLD. PMID- 17867303 TI - [IgG-kappa type multiple myeloma with cytoplasmic crystalline inclusions]. AB - An 82-year-old male was admitted to our hospital because of anemia with Hb 6.9/dl. The serum monoclonal IgG of the kappa type was detected. Bone marrow aspiration showed the presence of 38.9% atypical plasma cells with crystalline inclusions. These crystalline inclusions were stained with acid phosphatase, and remained unstained with MPO, PAS and Congo-Red staining. Immunofluorescence studies showed the plasma cells were positive for IgG-kappa type immunoglobulin and CD138. Electron microscopy revealed varying numbers of stick-like, rod shaped, rhomboid or rectangular crystals of a variety of lengths and sizes with a periodicity giving an appearance of longitudinal striation. The inclusions were most often surrounded by ribosomes. Some crystalline inclusions were located in the rough-surfaced endoplasmic reticulum. Their presence was probably due to an abnormality in the synthesis and/or secretion of immunoglobulin. PMID- 17867305 TI - [Human herpesvirus 6 encephalitis in a patient with adult T-cell leukemia/lymphoma]. AB - Human herpesvirus 6 (HHV-6) reactivates in immunocompromised patients, and HHV-6 encephalitis has often been reported as a complication of transplantation. We describe a 37-year-old woman with the acute type of adult T-cell leukemia/lymphoma who developed HHV-6 encephalitis before chemotherapy. The patient's main symptoms were disorientation and short-term memory loss. Magnetic resonance imaging of the brain showed a bilateral T2 prolongation within the temporal lobes, and HHV-6 DNA was detected in the cerebrospinal fluid (CSF). After treatment with ganciclovir, HHV-6 DNA disappeared from the CSF and the patient's symptoms gradually improved. HHV-6 encephalitis should be listed as a differential diagnosis of encephalopathy developing in immunocompromised patients. PMID- 17867304 TI - [Exacerbation of acute leukemia bearing isolated i(17q) along with proliferation of blasts with high BMI-1 expression]. AB - We report a case of acute leukemia with an isolated isochromosome 17q karyotypic abnormality, which may be transformed from myeloproliferative disease (MPD)/myelodysplastic syndrome (MDS). A 69-year-old male patient with 27% of blasts in the peripheral blood underwent hematological examinations including cytochemical staining of cells such as myeloperoxydase (MPO), surface marker study on blasts, chromosomal test and bcr-abl mRNA analysis. The cytological and molecular findings (MPO-positive, myeloid marker CD13 expression (67.3%) and megakaryocytic marker CD41 expression (24.8%)) indicated that the blasts were consistent with myeloid leukemic cells partially committed to megakaryocytes. He was diagnosed as having leukemic transformation from MPD/MDS based on history of leukocytosis and thrombocytosis, isolated i(17q), bcr-abl negative, hepatosplenomegaly, increased eosinophil/basophil count and cytologic dysplasia. Positivity of BMI-1 in CD34+ blasts was 25.8% at the diagnosis and anti-leukemic drugs including anthracyclines were effective for his disease control during 6 months. However, the CD34+ cells turned out to highly express BMI-1 (83.1%), and leukemic cells started to increase progressively following which the leukemic cells failed to respond efficiently to any anti-leukemic drugs. Thus, expression of BMI-1 was well correlated with the disease progression, growth ability of blasts and resistance to anti-cancer drugs, indicating that BMI-1 positivity in CD34+blasts is an excellent molecular marker for disease progression and prognosis in such patients. PMID- 17867306 TI - [Application of fiber tractography for neurosurgery]. PMID- 17867307 TI - [Examination of the hypothalamic artery during clipping operations of anterior communicating artery aneurysms]. AB - Relationships between hypothalamic arteries and anterior communicating artery aneurysms were examined in 34 cases treated by clipping operations, using the anterior interhemispheric approach. The directions of the aneurysmal domes and hypothalamic arteries were analyzed and divided into 2 groups. The different direction (D.D.) group involved cases in which a hypothalamic artery ran in a different direction to that of the dome of the aneurysm. The same direction (S.D.) group involved cases in which a hypothalamic artery ran parallel to the dome of the aneurysm. The D.D. group consisted of 15 cases, and the S.D. group consisted of 13 cases. In the remaining 6 cases, the hypothalamic artery was not found during the operation. In many cases of the D.D. group, the aneurysm was located anterior to the A2 portions of the bilateral anterior cerebral arteries, whereas, in all cases of the S.D. group, the aneurysm was located between or posterior to the bilateral A2 portions. We also investigated the flow direction of the anterior communicating artery in the S.D. group. The dominant A1 was defined as the side of internal carotid angiography in which the aneurysm was depicted on preoperative angiography. The flow direction of the anterior communicating artery was assumed to flow from the dominant A1 side to the recessive A1 side. Considering the flow direction of the anterior communicating artery, the hypothalamic artery was located downstream from the aneurysm in 9 cases and upstream in 3 cases. These results suggested that it is important to pay more attention to the downstream of the aneurysm to avoid injury of the hypothalamic artery in the S.D. group. For cases in which the hypothalamic artery was located upstream to the aneurysm, these aneurysms seemed to arise from the bifurcation of the anterior communicating artery and hypothalamic artery, and might be named hypothalamic artery aneurisms. PMID- 17867308 TI - [Clinical analysis of treatment and long-term outcome in 56 craniopharyngiomas]. AB - In order to improve QOL in patients with craniopharyngioma, retrospective analysis was performed to discover factors for influencing functional outcome and the best treatment strategy. 56 patients were treated between 1978 and 2005. They were initially treated with surgery and surgical cure was obtained in 29 patients (Group A). Subtotal tumor resection with prophylactic radiation was performed in 8 patients (Group D). Tumor recurrence was noted in 19 patients and stereotactic radiation or 2nd operation was performed in 11 patients (Group B). 2nd operation and fractionated radiation were undertaken in 8 patients (Group C). Endocrine, vision and recognition were scored from 2 to 0, respectively; 2 indicates normal, 1 partially disturbed, 0 fully disturbed. The mean score before treatment was 4.7 and the final score was 3.9. Factors leading to poor outcome included extrasellar origin, solid tumor, bad score before treatment, 2nd surgery for recurrence. The change of scores after the treatment was -0.1 in group A, -0.7 in Group B, -0.9 in Group C and 0.3 in Group D. Maximum tumor removal should be attempted with functional preservation. Subtotal removal with prophylactic radiation is recommended if the patient has normal hypothalamic function. PMID- 17867309 TI - [Radiographic characteristics of fibrous dysplasia of the clivus: a case report and review of the literature]. AB - Whereas fibrous dysplasia is a well-known, developmental skeletal disorder with a benign clinical course, fibrous dysplasia of the clivus is extremely rare and has seldom been reported. Differentiating this benign entity from more aggressive diseases involving the clivus is important for the proper management of lesions in this area. We here report a case of fibrous dysplasia of the clivus and discuss its radiographic features. The patient was 55-year-old male who had suffered from headache for months. Physical and neurological examinations found no abnormalities. The computed tomographic (CT) scan and magnetic resonance imaging (MRI) showed an abnormal mass lesion in the lower of the third clivus. On CT scan, the mass lesion exhibited a ground-glass appearance. The lesion was detected as hypointense and a mixture of hyperintense and isointense areas on T1 weighted and T2-weighted MRI, respectively. Heterogenous enhancement was noted after infusion of GD-DTPA. The patient underwent a transsphenoidal resection of the mass and the histopathologic diagnosis was fibrous dysplasia. PMID- 17867310 TI - [A rare case of intracranial meningioma with intratumoral metastatic breast cancers]. AB - We report an uncommon case of breast cancer metastasis to an intracranial meningioma. A 47-year-old female was admitted to our hospital due to general convulsion. She had undergone a radical operation for left breast cancer 4 years refore, and received postoperative adjuvant therapies. MRI revealed a solid well circumscribed tumor in the right frontal convexity. The patient underwent tumor resection successfully. The pathological examination revealed ductal carcinoma in the tissue of a transitional meningioma. Tumor-to tumor metastasis is a rare event. Literature review and discussion of such an uncommon occurrence was presented. PMID- 17867311 TI - [A case report of severe cerebral sinus thrombosis treated by mechanical disruption using rheolytic catheter with balloon]. AB - A 61-year-old man presented with consciousness disorders. Computed tomography revealed bilateral frontal SAH and hematoma in the right temporo-parietal region. His condition deteriorated despite conservative treatment and hematoma became enlarged. The angiographic diagnosis was extensive sinus thrombosis from the superior sagittal sinus to the bilateral transverse sinus. Therefore, mechanical clot disruption was performed under systemic anticoagulation using PTA balloons catheter and a rheolytic catheter via the right internal jugular vein. Excellent angiographic results were obtained, and the patient recovered gradually. Six months after treatment, the patient had only upper quadrant hemianopsia and no other neurologic deficit. Our experience suggests that mechanical clot disruption with systemic anticoagulation as a safe effective treatment for cerebral sinus thrombosis, especially in patient whom had large intraparenchymal hematoma. PMID- 17867312 TI - [Skull metastasis of hepatocellular carcinoma successfully treated by intraoperative photodynamic diagnosis using 5-aminolevulinic acid: case report]. AB - There have been no studies on photodynamic diagnosis (PDD) using 5-aminolevulinic acid (5-ALA) in patients with metastatic skull tumors. Here, we present a case of skull metastasis of hepatocellular carcinoma (HCC) successfully treated by intraoperative PDD using 5-ALA. A 63-year-old man with HCC presented with a subcutaneous mass in the left occipital region. CT showed a hyperdensity mass and severe osteolytic change in the left side of the occipital bone. MRI revealed an extra-axial enhanced mass that compressed the left occipital lobe and enhancement was spreading to the adjacent subcutaneous soft tissue. In order to intraoperatively evaluate the extent of tumor invasion, PDD using 5-ALA was performed. Intraoperative PDD comfirmed that the tumor itself was highly fluorescent. Surgery was completed after comfirming the absence of residual fluorescence in the surgical field. The tumor was diagnosed HCC. Histopathological analysis confirmed that PDD accurately assessed the extent of tumor invasion. The patient was discharged home at 10 days after surgery. PDD using 5-ALA is convenient and inexpensive, and because adverse reactions are minimal, it may be useful in not only malignant glioma, but also other brain tumors. PMID- 17867313 TI - [A case of amebic brain abscess]. AB - Amebic brain abscess is a rare and usually fatal complication of Entamoeba histolytica infections. We successfully treated a patient with this infection accompanied by brain, liver and pulmonary abscesses. Treatment consisted of administration of metronidazole through a nasogastric tube, and drainage of the brain abscess. A 51-year-old male patient presented with a two-week history of fever, severe back pain, and chest pain. Liver and pulmonary abscesses were drained upon admission. Biopsy of the colon showed infection by Entamoeba histolytica. After oral administration of metronicazole, the patient became somnolent, and neurological examination showed left side weakness. CT scan and MRI of the brain disclosed an abnormal lesion in the right basal ganglia. He was then transferred to our department, where stereotactic aspiration with drainage of the brain abscess was performed. The abscess was filled with reddish purulent material. Treatment with metronidazole (1,200 mg daily) for 18 days resulted in almost complete resolution of the intracerebral lesion and survival of the patient without any neurological deficits. His general condition improved dramatically, and he was discharged from our hospital 2 months later. Only 14 cases with amebic brain abscess associated with Entamoeba histolytica infection who recovered after treatment have been reported. We suggest amebic brain abscess should be taken into consideration for patients with brain abscess with a history of dysenteric illness especially since early diagnosis and aggressive management is likely to result in a cure. PMID- 17867314 TI - [A case of multiple meningiomas: two lesions have different clinicopathological features, respectively]. AB - A 60-year-old man presented with general convulsion. Computed tomographic (CT) scans and magnetic resonance (MR) imaging showed two meningiomas located at the bilateral frontal convex respectively. In spite of the similar tumor size, the left tumor only had marked peritumoral edema. Angiography showed that the left lesion was more amply supplied from the internal carotid artery than the right one was. These two tumors were totally resected. The left tumor adhered to the surrounding brain tissue more intensely than the right one. Both tumors were microscopically diagnosed as angiomatous meningioma. The left tumor cells have a stronger immunopositivity for VEGF than the right ones. We suggest that pial blood supply, adhesion to brain tissue and VEGF expression influence the development of meningioma-associated peritumoral edema. PMID- 17867315 TI - [Cell replacement therapy with human ES cells for the treatment of Parkinson's disease]. PMID- 17867316 TI - HIV dementia a challenge to developing countries. PMID- 17867317 TI - Abbott Laboratories backlists Thailand from new AIDS/HIV drugs. PMID- 17867318 TI - Uganda's early gains against HIV eroding. PMID- 17867319 TI - Research governance: new hope for ethics committees? AB - For many years there has been discussion regarding the problems confronting our current ethics review system. Commentators have identified numerous issues that threaten the sustainability of Australia's voluntary HREC system. Various ad hoc solutions to these problems have been posed, but have not resulted in any significant advances. However, in recent years, discourse regarding research governance has become prominent in the Australian research environment. The application of research governance principles is gaining momentum amongst the regulators of research, including research institutions and their governing bureaucracies. We argue that this is potentially the most significant development in several years towards creating a sustainable HREC system in Australia. The recognition by research institutions and their governing bureaucracies that the responsibility for overall research governance lies with them, rather than solely with their HRECs, is leading to a range of initiatives which should significantly lessen the burden on Australian ethics committees, and improve their ability to undertake their core task of reviewing the ethical aspects of research proposals. PMID- 17867320 TI - Detecting bias in biomedical research: looking at study design and published findings is not enough. PMID- 17867321 TI - Articulation and transparency of decision-making by Human Research Ethics Committees. AB - In this paper, we argue that Human Research Ethics Committees (HRECs) have an obligation to clearly articulate, document and be accountable for the reasons for their decisions, and to make their documentation available for external scrutiny. We advance two arguments to support this claim. The first is that this is a legal obligation--that HRECs, by virtue of the way they are established under legislation, are required by law to provide statements of reasons. The second is an ethical argument--even if the legal argument is flawed, there are still compelling ethical reasons for HRECs to operate in this way. We then give an example of what a statement of reasons from an HREC might look like, and urge HRECs to consider whether their decision-making and documentation could meet this model. PMID- 17867322 TI - Mind the gap: Griffith University's approach to the governance of ethical conduct in human research. AB - It is perhaps not coincidental that, at the same time the apparent institutional risks associated with the conduct of human research are increasing, so are the complaints from researchers about research ethics committees. Rather than seeking to implement systems that more efficiently catch wrong-doing, in 2003 Griffith University began implementing an alternative approach. This new approach focused on resourcing the reflective practice of researchers through every stage of their work--well before, and long after, they seek ethical clearance for that work. Institutions have a key role to play in human research ethics, and this can be usefully situated within the broader framework of the institution's governance framework. This paper summarises the new approach that Griffith University adopted in 2003, the implementation of this 'model', the experience to date, and the road ahead. PMID- 17867323 TI - The patient, the doctor and the family as aspects of community: new models for informed consent. AB - Filial obligation and its implications have been little-debated in ethics. The basis of informed consent in libertarian positions may be challenged by inclusion of others beyond the immediate doctor-patient relationship. Some of the literature arguing for and against filial duty, including feminist literature, is presented as a backdrop to the argument that a patient's family, and further, his or her community, contains the source of a broader perspective regarding decisions concerning his or her medical treatment. Communitarian models allow for a medical decision to be owned by some or all stakeholders in patient outcomes. Although such a position undoubtedly confronts traditional notions of autonomy, it offers an alternative that may positively impact the practice of medicine by providing a more holistic treatment context. New models premised on shared decision-making will be presented as frameworks that may provide a theoretical basis for greater physician input into medical decisions that impact a patient's family members and in more global terms, his or her community. PMID- 17867324 TI - Enhancing children's intelligence: do the means matter morally? AB - This article deals with the prospect of genetically enhancing intelligence. We identify and contrast social attitudes (disapproval) to the use of future genetic technology with social attitudes (approval) for environmental methods of enhancing intelligence. Using various forms of the argument that the means by which enhancement is achieved has moral significance, we look for differences that could justify the different attitudes. We find that the different attitudes cannot be ethically justified. We predict that the lack of ethical justification for distinguishing between means of enhancement is likely to result in the eventual acceptance of genetic enhancement of intelligence. PMID- 17867325 TI - [Cervical cancer screening in Poland and worldwide]. AB - High cervical cancer morbidity remains an unresolved epidemiologic problem in Poland. Prevention programs used in the past years did not lead to significant decrease in cervical cancer mortality and morbidity. Countries that introduced active prevention programs several decades ago achieved significant decrease by up to 80%, in the cervical cancer morbidity. We present in this paper the principles of the screening program introduced in Poland in 2006 and compare it with the screening models applied in the other countries. The special attention is drawn to the age at which screening is commenced and stopped as well as to the screening intervals. Advantages and disadvantages of the PAP smear are discussed in great details. Additionally the potential role of HPV DNA testing is discussed, including the possibility of replacement of cytological tests with HPV testing. PMID- 17867326 TI - [The safety and tolerance of isoflavones (Soyfem) administration in postmenopausal women]. AB - INTRODUCTION: In recent years, considerable attention has been paid to isoflavones and their proprieties to alleviate the climacteric symptoms. The goal of this study was to evaluate the efficacy of standardized isoflavones extract (Soyfem) in moderate and medium-severe climacteric syndrome. MATERIAL AND METHODS: 555 postmenopausal women were recruited for the study. Out of this group, 169 women completed the study (12-month observation period). The patients were classified according to the intensity of climacteric symptoms (< or =34 points in Kupperman index). 1 or 2 tablets of Soyfem were administered twice a day,. RESULTS: A regular decrease of Kupperman index value and improvement of life quality were observed in the group of 169 postmenopausal women. We have noted a decrease in the intensity and number of hot flushes, diaphoresis (p < 0.05), diminished sleep disturbances (p < 0.05), decreased headache, dizziness, and arthrosis pain. The diminished intensity of tiredness, palpitation and breathlessness have been also observed (p < 0.05). 80% of all investigated women noted the regression of paresthesis, 20% indicated the decreased number of paresthesis (p < 0.05). Influence of Soyfem on the variability and moderation of depressive mood (p < 0.05) have been also positive evaluated by patients. CONCLUSIONS: Administration of Soyfem in the dosage 52 to 104 mg/24 hours (2 times daily 1 or 2 tablets) is a safe and effective therapy in the postmenopausal women with moderate and medium-severe climacteric syndrome evaluated according to the Kupperman index. Administration of Soyfem is connected with a good compliance and correlated with well-being in the investigated women allowing a long-term administration. PMID- 17867327 TI - [Activity of matrix metalloproteinases -2 and -9 (MMP-2 and MMP-9) and content of their tissue inhibitors in endometrial cancer--a preliminary study]. AB - OBJECTIVES: Matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) are enzymes degrading collagen type IV and other components of the basement membrane. Their activity is suppressed by tissue inhibitors of metalloproteinases--TIMP-1 and TIMP-2. Substantial evidence indicates that MMP2 and MMP-9 play an important role in the spread of malignant tumours. The aim of the study was to evaluate the activity of MMP-2 and MMP-9 and contents of their inhibitors: TIMP-1 and TIMP-2 in endometrial cancer and normal endometrium. MATERIAL AND METHODS: Material for the study comprised 28 samples of endometrial cancers and 15 samples of normal endmetrium. A two-step method for extraction of MMPs was applied. The activity of MMP-2 and MMP-9 was measured with semi-quantitative zymography. TIMP-1 and TIMP-2 contents were measured with ELISA method. RESULTS: Mean activity and activation ratio of MMP-9 was significantly higher in endometrial cancers compared with normal myometrium, whereas mean activity and activation ratio of MMP-2 did not differ significantly between investigated groups. Mean content of TIMP-1 and TIMP 2 did not differ between cancer and control tissues. No unequivocal association between activity of investigated MMPs or contents of their inhibitors and clinicopathological features of endometrial cancers was observed. CONCLUSIONS: Results of the study suggest that MMP-9 may play an important role in the progression of endometrial cancer, whereas MMP-2 does not seem to be involved in this process. Action of MMP-9 may be further enhanced by relative deficiency of TIMP-1. PMID- 17867328 TI - [Clinical assessment of selected vascularization attributes of adnexal masses in preoperative prediction of tumor malignancy]. AB - OVERVIEW: Preoperative differential diagnosis of adnexal masses has been a challenge for researchers for years. Prediction of tumor malignancy is essential for selection of optimal treatment with lowest risk for patient. Assessment of various tumor vascularization attributes, using color Doppler semi-quantitative analysis, can be helpful for malignancy differentiation. OBJECTIVES: To assess value of selected vascularization attributes of adnexal masses in preoperative prediction of tumor malignancy. MATERIALS AND METHODS: This study included 521 women diagnosed and treated for adnexal masses (181 malignant and 340 benign) in Obstetrics and Gynecology Hospital of University of Medical Sciences in Poznan between 1994 and 2004. All of them underwent color Doppler examination using Aloka 2000 and 5500 devices (vaginal probes 5,0-6,5 MHz, abdominal probes 3,5-5 MHz) with evaluation of such attributes as: vessels count, localization and structure; semi-quantitative scale was also constructed basing on these parameters. RESULTS: There was a significantly higher number of vessels (cut-off value=4; p < 0.0001), central vessels localization (p < 0.0001) and irregular structure of vessels (p < 0.0001) in patients with confirmed malignant tumor. Constructed semi-quantitative Doppler scale resulted in highest diagnostic accuracy (cut-off value = 3; p < 0.0001). CONCLUSIONS: Central vessels localization was the single most significant attribute in tumor malignancy differentiation. Constructed semi-quantitative Doppler scale resulted in highest diagnostic accuracy and can be a useful tool in preoperative prediction of tumormalignancy. PMID- 17867329 TI - [The efficacy of SUI treatment with Burch colposuspension evaluated with use of ITT analysis]. AB - OBJECTIVES: Search for methods of assessment of effects of SUI treatment, which goal is to minimize risk of bias, are inconclusive and remain the subject of investigation. DESIGN: The aim of the study was to analyze the influence of application of different methods of efficacy measurement of SUI treatment with use of Burch colposuspension on final conclusions concerning the treatment effects. MATERIAL AND METHODS: Prospective investigation was carried out among 50 women with SUI symptoms II or Ill degree, scheduled for Burch colposuspension. The analysis of obtained results was carried out with use of ITT and modified ITT. To compare, therapy effects were explored with the use of principles which have been, until quite recently, most often used in urogynecology. RESULTS: Differences in percentage of cured, based on results of several urogynecologic examinations according to method of analysis (previously used method, ITT, modified ITT), have oscillated between 3% to 20%. CONCLUSIONS: (1) While selecting diagnostic methods to analyze SUI treatment effectiveness, potential problems with obtaining complete data after the treatment should be taken into account. (2) In order to minimize statistic bias, the usage of few methods of analysis of obtained results is highly recommended. PMID- 17867330 TI - [The influence of SUI operative treatment with use of IVS tape on quality of life]. AB - OBJECTIVES: Real influence of urinary incontinence symptoms and adopted modes of treatment on patient's quality of life is not known. DESIGN: Assessment of influence of operative SUI treatment with the use of IVS tape on patient's quality of life. MATERIAL AND METHODS: Prospective study was conducted among 57 patients with SUI symptoms II and III degree (type III according to Blavais), who were classified to apply IVS tape. Diagnostic investigations were completed by questionnaires: IIQ-7 and UDI-6, which were filled by patients. In analysis there were included results obtained before the operation and 6 months after procedure. RESULTS: We recognized women as cured: based on physicians anamnesis--80.7% of patients, according to UDI-6 --71.93%. Half year after operation relevant improvement of quality of life, evaluated by IIQ-7 questionnaire, showed 89.47%. Improvement of quality of life correlated with lack of SUI symptoms in anamnesis (r = 0.631; p < 0.001) and in UDI-6 questionnaire (r = 0.597; p < 0.001). CONCLUSIONS: (1) Operation with the use of IVS tape is effective according to improvement of quality of life in majority of patients treated due to SUI. (2) Efficacy of operative treatment in domain with SUI symptoms correlates with influence of procedure on quality of life. (3) Assessment of SUI operative treatment should include analysis of SUI symptoms and their influence on quality of life, achieved upon standardized questionnaires filled by patients. PMID- 17867331 TI - [Evaluation of pregnancy-associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (beta hCG) levels and sonographic assesement of fetal nuchal translucency (NT) in singleton pregnancies between 11 and 14 weeks of gestation--Polish multi-centre research]. AB - Evaluation of pregnancy-associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (beta hCG) levels and sonographic assessment of fetal nuchal translucency (NT) in singleton pregnancies between 11 and 14 weeks of gestation--Poland's multi-centers research. OBJECTIVES: Pregnancy associated plasma protein A has been reported to be low in Down syndrome affected pregnancies during the first trimester of pregnancy. Enlarged nuchal translucency (NT) is observed in about 80% of fetuses affected with chromosomal abnormalities and congenital heart defects (CHD). MATERIAL AND METHODS: The aim of this study were to determine value and the medians of free beta-human chorionic gonadotropin (beta-hCG) and pregnancy associated plasma protein-A (PAPP-A) and nuchal translucency thickness in the first trimester in a prospective study of a non selected Polish population. RESULTS: All examinations have been performed according to the Fetal Medicine Foundation (FMF) rules. We have included 800 women between 11 weeks 0 days and 13 weeks 6 days gestation into a biochemical examination. Women booked into the clinic were offered screening, using a combination of maternal serum free beta-hCG and pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency thickness. The maternal serum were measured using the Kryptor analyzer (Brahms Diagnostica). All pregnant women have been divided into 2 groups younger than (first group) and older than (second group) 35 years of age. CONCLUSIONS: Nomogrames for free beta-hCG and PAPP-A levels in physiological pregnancy between 11(+0) and 13(6) weeks were determined in the examined population. A positive correlation between PAPP-A and CRL levels, as well as a weak negative correlation between free beta-hCG and CRL, were demonstrated. PMID- 17867332 TI - [Diagnostic techniques in breast cancer detection. Part I: imaging methods and their modifications]. AB - This publication contains an overview of the imaging techniques and the related technologies utilized in breast cancer diagnosis. It describes both those known for tens of years as well as the ones developed recently thanks to the new technological developments. An integration and coexistence of the diagnostic methods from classical mammography to the computerized laser mammography has become essential in order to cope with the requirements of early detection of breast tumours, which is a precondition of successful treatment and longer survival periods upon which patients rely. PMID- 17867333 TI - [Present conceptions of etiopathogenesis of polycystic ovary syndrome]. AB - Polycystic ovary syndrome is one of the most common endocrinopathies, occurring in women in reproductive ages. Despite a long history of studies on PCOS, its etiology is still unknown and the very definition remains controversial. This paper presents the most modern concepts which explain the pathophysiology of PCOS, concentrating on a gonadotropic-ovarian and an insulin-dependent model, the roles of a inflammatory state, an endothelium injury and an oxidative stress in PCOS development, as well as postulated genetic mechanisms. The hypo-thetical model of PCOS etiopathogenesis is proposed on the base of the discussed partial concepts. PMID- 17867334 TI - [Early or late amniocentesis--which method is safer?]. AB - OBJECTIVES: Whether or not to perform early or late amniocentesis remains questionable due to higher fetal loss and the rate of talipes equinovarus after early amniocentesis. MATERIAL AND METHODS: We have compared the course of pregnancy, delivery and the condition of the newborns in patients after early and late amniocentesis in the group of women who had undergone amniocentesis in the Department of Obstetrics of Medical University of Gdansk between the years 1996 2003. RESULTS: Early amniocentesis was performed in 302 patients (55.9%), late amniocentesis in 302 patients (44.1%). Fetal loss occurred in 8 pregnancies (2.6%) after early amniocentesis and in 2 cases (0.8%) after late amniocentesis (P = 0.10). There was no statistically significant difference between early and late amniocentesis, comparing complications following the procedure in the first 3 weeks after amniocentesis: lower abdominal pain, spotting, bleeding, leakage of amniotic fluid. Mean duration of pregnancy in patients after early amniocentesis was 38.5 +/- 3.9 and 38.4 +/- 3.3 weeks in late amniocentesis group. There was no statistically significant difference between these groups in the type of delivery and premature delivery rate. Frequency of pneumonia and the respiratory infections in newborns were comparable in two groups (6.8% vs. 4.8%). There was only one case of talipes equnovarus in a fetus after late amniocentesis and one case of congenital dysplasia of the hip in a fetus after late amniocentesis, too. There were not any such defects in a group after early amniocentesis. CONCLUSIONS: The type of amniocentesis--early or late--has not got any influence on the frequency of complicattions after amniocentesis. PMID- 17867335 TI - [Intrahepatic cholestasis of pregnancy: a disorder with increased fetal risks. Part II: fetal condition and medical management]. AB - The aim of this review was to present recent information about the fetal condition in cases of intrahepatic cholestasis of pregnancy. A relatively mild course of maternal disease does not predict fetal well-being accurately. Increased risk of sudden intrauterine death was emphasized, implicating the need for more stringent obstetric monitoring of fetal condition in this disorder. A pathogenetic mechanism leading to sudden deterioration of fetal wellbeing was proposed and discussed. Current recommendations regarding medical management of intrahepatic cholestasis of pregnancy were also presented. PMID- 17867336 TI - [Renal insufficiency in diabetic pregnancy with nephropathy]. PMID- 17867337 TI - [Practical cardiotocography]. PMID- 17867338 TI - Innervation of the triangular fibrocartilage complex of the human wrist: quantitative immunohistochemical study. AB - The distribution of neural elements in the triangular fibrocartilage complex (TFCC) of the human wrists was studied via immunohistochemical staining of protein gene product (PGP) 9.5 and calcitonin gene-related peptide (CGRP). Articular branches projecting to the TFCC arose from the dorsal branch of the ulnar nerve in all wrists examined. The TFCC is subdivided into the following six regions: the articular disc proper (ADP), meniscus homolog (MH), radio-ulnar ligament (RUL), loose part of ulnar collateral ligament (lUCL), dense part of ulnar collateral ligament (dUCL), and internal portion (IP). The IP consists of a mixture of dense and loose connective tissues enclosed by the ADP, MH, RUL, and UCL, and resides deep in the prestyloid recess, which is a pit in the MH. The densities of PGP 9.5-positive neural elements, including free nerve endings, single nerve fibers, nerve fascicles, and perivascular neural nets, were significantly higher in the IP than in other regions. Some of the neural elements except for the perivascular neural nets were positive for CGRP. The high density of neural elements in the IP suggests that sensory nerves projecting to the TFCC enter into the IP and from there distribute to adjacent regions such as the MH and RUL. Free nerve endings are responsible for pain transmission. The high density of free nerve endings in the IP suggests that the IP is a source of ulnar side wrist pain. PMID- 17867339 TI - Anomaly with no right ventral root at the seventh cervical segment in humans: gross anatomical and neuroanatomical study. AB - The cadaver of an 89-year-old woman who had died of cerebral apoplexy and which was dedicated to anatomy practice for medical students at Kumamoto University, was found to have complete lack of the right ventral root of the seventh cervical segment (C7). Observation of the peripheral spinal nerve indicated that the branch, which appeared to be a descending collateral of the ventral root of C6, became confluent with the dorsal root of C7 at the point just distal to the dorsal root ganglion. Following this confluence, new fiber elements ran out of the intervertebral foramen as the seventh cervical nerve. More peripherally, this fiber bundle joined the brachial plexus, its outward appearance was normal in the manner of ramification and each nerve's supply to muscles. Additionally, the inside view of the spinal cord of C6, C7 and C8 was examined neuroanatomically. Nissl staining of transverse sections at C7 (block 2) showed that motor neurons existed in the right anterior horn and their histological features were normal. Subsequently, horizontal sections were made from the two blocks, each of which contained C6/C7 (block 1) or C7/C8 (block 3), and were treated dually with Nissl and myelin staining. These sections also had a normal picture of cells and myelinated fibers on the right side as compared with those on the left side. The results suggested that motor neurons of the right C7 had a normal supply to the targets, although the trajectory of their axons in the spinal cord was obscure. PMID- 17867340 TI - Anatomical landmarks: dimensions of the mastoid air cell system in the Mediterranean population. Our experience from the anatomy of 298 temporal bones. AB - The mastoid apophysis originates from a recent phylogenetic formation, associated with the standing attitude and it is currently considered as an evolution of the bone super-structures. The aim of the present study was to measure the diameters of the mastoid and the temporal bone in the Greek adult population. A total of 298 temporal bones from 149 cadavers (74 male, 75 female) were examined. The distances between six landmarks were measured by means of a pachymeter on both vertical and transverse axes of the mastoids and the temporal bone. The estimated mean values for each dimension were as follows: vertical diameter, 2.37 +/- 0.42 cm; transverse diameter, 2.33 +/- 0.51 cm; anterior margin, 2.12 +/- 0.67 cm; posterior margin, 1.96 +/- 0.55 cm; oblong diameter, 10.30 +/- 0.60 cm; while the mean distance between the mastoid apex and mandibular fossa calva was 3.67 +/- 0.35 cm. Gender differences were detected for the vertical (P < 0.001), the transverse diameter of the mastoid (P < 0.001), the anterior (P < 0.001) and the posterior margin of the mastoid (P < 0.001). In both genders, the vertical diameter of the mastoid was positively correlated with the transverse diameter, as well as with its anterior and posterior margins. In the present study, direct measurements of the mastoid and temporal bone in a Mediterranean population are reported. This description may facilitate a more accurate surgical approach to the temporal bone structures. PMID- 17867341 TI - Relationship between the distribution of myofibroblasts, and stellar and circular scar formation due to the contraction of square and circular wound healing. AB - Square skin wounds can heal to form a stellar scar with four protrusions at the four angles, whereas circular wounds can heal to form an ellipsoid scar. It is not clear why these differences occur and the aim of the present study was to clarify this phenomenon. Two square or circular full-thickness skin wounds were made on the dorsum of mice, and covered with hydrocolloid dressing. They were observed from day 0 to 15 after wounding, and used to prepare paraffin sections stained with anti-alpha-smooth muscle actin antibody to detect myofibroblasts. The square wound was transiently enlarged by edema and skin tension on day 3, at which time the angles became round, and thus the square form became more circular. Thereafter, the wound contracted rapidly and the circular form was maintained until day 11. On day 11 distinct angles appeared where the scar formation had progressed further, and there were fewer myofibroblasts than in any other section. A stellar scar with protrusions from the four angles was formed on day 15, when myofibroblasts almost disappeared in the protrusions. This indicates that due to the earlier disappearance of myofibroblasts and earlier scarring in the angles of the square wound, the scar angle cannot be pulled into the center of the wound but residual myofibroblasts on the side can pull the side into the center due to myofibroblastic contraction and consequently a stellar scar is formed. Thus, the earlier disappearance of myofibroblasts in the angles is very important for the formation of stellar scars. PMID- 17867342 TI - Three-dimensional analysis of inner ear development in human embryos. AB - The development of the inner ear is difficult to understand morphologically, because it proceeds in a complicated manner. Chronological 3-D reconstructed models of the inner ear primordium in human embryos (Carnegie stage 16-22) were created from the histological serial sections in the Kyoto Collection of Human Embryos using 3-D-reconstruction software on a personal computer. The endolymphatic duct begins to extend at stage 18 and continues to extend. The formation of the anterior and posterior semicircular ducts begins at stage 17. The upper lateral region of the otic pouch starts to sink inward at stage 17 and then the epithelia of both sides face and fuse with each other. The fusion disappears and the mesenchyme appears in the primordium, which looks like a hole in the otic pouch at stage 18. The mesenchyme begins to enlarge in the otic pouch at late stage 18, and continues to enlarge until the formation of the loop of semicircular ducts at stage 19. The lateral semicircular duct is formed similarly at stages 18 and 19. In the mesenchyme of the lateral semicircular duct, we found apoptotic death near the epithelium of the otic pouch at late stage 19. The cochlear duct already begins to extend at stage 16. First it extends to the opposite direction of the future cochlear rotation at stage 16 and 17, and then turns to the future rotating direction at stage 18. The cochlear duct initiates rotation at late stage 19. The cochlear duct continues to rotate and forms approximately one winding at stage 22. PMID- 17867343 TI - Temporary accumulation of glycogen in the epithelial cells of the developing mouse submandibular gland. AB - Temporary accumulation of glycogen in the epithelial cells of the developing mouse submandibular gland was examined under light microscopic histochemistry and electron microscopy. To avoid loss of water-soluble glycogen during histological tissue preparation, fixation with ethanol and embedding in hydrophilic glycol methacrylate resin was used for light microscopy, and high-pressure freezing/freeze substitution for electron microscopy. Glycogen was detected on periodic acid-Schiff stain, periodic acid-thiosemicarbazide-silver proteinate reaction, and the digestion test with alpha-amylase. On embryonic day 14, glycogen began to accumulate in the proximal portions of the developing epithelial cords. On embryonic day 17, marked glycogen particles were seen at the basal portion of the ductal epithelial cells and an abrupt increase of glycogen accumulation occurred in the secretory cells in the terminal bulbs. Ultrastructural observation indicated large clumps of glycogen particles localized in the basal portion of the terminal bulb cells. The initiation of glycogen accumulation preceded the formation of lumens in the ducts and terminal bulbs. Furthermore, proliferation analysis by bromodeoxyuridine labeling showed that this glycogen accumulation followed the cessation of the epithelial cell proliferation. Postnatally, glycogen accumulation in the terminal bulbs became gradually inconspicuous and completely disappeared by postnatal day 3, but that in the ducts was retained until around postnatal day 12. Temporary glycogen accumulation after the cell proliferation and before/during the lumen formation and secretory granule formation suggests significant involvement of the carbohydrate metabolism in the organogenesis of the submandibular gland. PMID- 17867344 TI - Bilateral variations of the vertebral arteries: the left originating from the aortic arch and the left and right entering the C5 transverse foramina. AB - During the dissection course for second year medical students at the University of Toyama in 2005, we encountered variations of the bilateral vertebral arteries: the left directly came off from the aortic arch as the third branch between the left common carotid artery and the left subclavian artery and entered the transverse foramen of C5, instead of C6, whereas the right originated from the right subclavian artery and entered the transverse foramen of C5. The present vertebral artery of each side was possibly formed by the 6th cervical intersegmental artery linked with the longitudinal anastomoses between the cervical intersegmental arteries. Detailed knowledge of vertebral artery variations is crucially important for surgical treatment of blood vessels in the brain, neck and chest. PMID- 17867345 TI - Bilateral subclavian arteries passing in front of the scalenus anterior muscles. AB - Herein, we present a very rare case of bilateral subclavian arteries passing in front of the scalenus anterior muscles in a cadaver. This abnormality was observed in a 73-year-old Japanese male cadaver during a dissection session for students in 2004 at Osaka Dental University. The bilateral scalenus anterior muscle originated from the anterior tubercle of the transverse processes of the fifth and sixth cervical vertebrae and inserted into the scalene tubercle of the first ribs. The right scalenus minimus muscle was observed, but no left scalenus minimus muscle was observed. The aortic arch was a type A according to Adachi's classification. The origin of the internal thoracic artery was distal to that of the thyrocervical trunk. The bilateral brachial plexuses was formed by the union of the ventral rami from the fifth cervical to the first thoracic nerves and passed between the scalenus anterior and the scalenus medius muscles. To our knowledge, such a case has not been reported previously. PMID- 17867346 TI - Mixed-band wavelet-chaos-neural network methodology for epilepsy and epileptic seizure detection. AB - A novel wavelet-chaos-neural network methodology is presented for classification of electroencephalograms (EEGs) into healthy, ictal, and interictal EEGs. Wavelet analysis is used to decompose the EEG into delta, theta, alpha, beta, and gamma sub-bands. Three parameters are employed for EEG representation: standard deviation (quantifying the signal variance), correlation dimension, and largest Lyapunov exponent (quantifying the non-linear chaotic dynamics of the signal). The classification accuracies of the following techniques are compared: (1) unsupervised k-means clustering; (2) linear and quadratic discriminant analysis; (3) radial basis function neural network; (4) Levenberg-Marquardt backpropagation neural network (LMBPNN). To reduce the computing time and output analysis, the research was performed in two phases: band-specific analysis and mixed-band analysis. In phase two, over 500 different combinations of mixed-band feature spaces consisting of promising parameters from phase one of the research were investigated. It is concluded that all three key components of the wavelet-chaos neural network methodology are important for improving the EEG classification accuracy. Judicious combinations of parameters and classifiers are needed to accurately discriminate between the three types of EEGs. It was discovered that a particular mixed-band feature space consisting of nine parameters and LMBPNN result in the highest classification accuracy, a high value of 96.7%. PMID- 17867347 TI - Pulse morphology visualization and analysis with applications in cardiovascular pressure signals. AB - We present a new analysis and visualization method for studying the functional relationship between the pulse morphology of pressure signals and time or signal metrics such as heart rate, pulse pressure, and means of pressure signals, such as arterial blood pressure and central venous pressure. The pulse morphology is known to contain potentially useful clinical information, but it is difficult to study in the time domain without the aid of a tool such as the method we present here. The primary components of the method are established signal processing techniques, nonparametric regression, and an automatic beat detection algorithm. Some of the insights that can be gained from this are demonstrated through the analysis of intracranial pressure signals acquired from patients with traumatic brain injuries. The analysis indicates the point of transition from low-pressure morphology consisting of three distinct peaks to a high-pressure morphology consisting of a single peak. In addition, we demonstrate how the analysis can reveal distinctions in the relationship between morphology and several signal metrics for different patients. PMID- 17867348 TI - Automatic identification and removal of scalp reference signal for intracranial EEGs based on independent component analysis. AB - The pursuit of an inactive recording reference is one of the oldest technical problems in electroencephalography (EEG). Since commonly used cephalic references contaminate EEG and can lead to misinterpretation, extraction of the reference contribution is of fundamental interest. Here, we apply independent component analysis (ICA) to intracranial recordings and propose two methods to automatically identify and remove the reference based on the assumption that the scalp reference is independent from the local and distributed intracranial sources. This assumption, supported by our results, is generally valid because the reference scalp electrode is relatively electrically isolated from the intracranial electrodes by the skull's high resistivity. We point out that the linear model is underdetermined when the reference is considered as a source, and discuss one special underdetermined case for which a unique class of outputs can be separated. For this case most ICA algorithms can be applied, and we argue that intracranial or scalp EEGs follow this special case. We apply the two proposed methods to intracranial EEGs from three patients undergoing evaluation for epilepsy surgery, and compare the results to bipolar and average reference recordings. The proposed methods should have wide application in quantitative EEG studies. PMID- 17867349 TI - Evaluation of respiratory muscles activity by means of cross mutual information function at different levels of ventilatory effort. AB - Analysis of respiratory muscles activity is an effective technique for the study of pulmonary diseases such as obstructive sleep apnea syndrome (OSAS). Respiratory diseases, especially those associated with changes in the mechanical properties of the respiratory apparatus, are often associated with disruptions of the normally highly coordinated contractions of respiratory muscles. Due to the complexity of the respiratory control, the assessment of OSAS related dysfunctions by linear methods are not sufficient. Therefore, the objective of this study was the detection of diagnostically relevant nonlinear complex respiratory mechanisms. Two aims of this work were: (1) to assess coordination of respiratory muscles contractions through evaluation of interactions between respiratory signals and myographic signals through nonlinear analysis by means of cross mutual information function (CMIF); (2) to differentiate between functioning of respiratory muscles in patients with OSAS and in normal subjects. Electromyographic (EMG) and mechanomyographic (MMG) signals were recorded from three respiratory muscles: genioglossus, sternomastoid and diaphragm. Inspiratory pressure and flow were also acquired. All signals were measured in eight patients with OSAS and eight healthy subjects during an increased respiratory effort while awake. Several variables were defined and calculated from CMIF in order to describe correlation between signals. The results indicate different nonlinear couplings of respiratory muscles in both populations. This effect is progressively more evident at higher levels of respiratory effort. PMID- 17867350 TI - Estimation of muscle fiber conduction velocity with a spectral multidip approach. AB - We propose a novel method for estimation of muscle fiber conduction velocity from surface electromyographic (EMG) signals. The method is based on the regression analysis between spatial and temporal frequencies of multiple dips introduced in the EMG power spectrum through the application of a set of spatial filters. This approach leads to a closed analytical expression of conduction velocity as a function of the auto- and cross-spectra of monopolar signals detected along the direction of muscle fibers. The performance of the algorithm was compared with respect to that of the classic single dip approach on simulated and experimental EMG signals. The standard deviation of conduction velocity estimates from simulated single motor unit action potentials was reduced from 1.51 m/s [10 dB signal-to-noise ratio (SNR)] and 1.06 m/s (20 dB SNR) with the single dip approach to 0.51 m/s (10 dB) and 0.23 m/s (20 dB) with the proposed method using 65 dips. When 200 active motor units were simulated in an interference EMG signal, standard deviation of conduction velocity decreased from 0.95 m/s (10 dB SNR) and 0.60 m/s (20 dB SNR) with a single dip to 0.21 m/s (10 dB) and 0.11 m/s (20 dB) with 65 dips. In experimental signals detected from the abductor pollicis brevis muscle, standard deviation of estimation decreased from (mean +/- SD over 5 subjects) 1.25 +/- 0.62 m/s with one dip to 0.10 +/- 0.03 m/s with 100 dips. The proposed method does not imply limitation in resolution of the estimated conduction velocity and does not require any iterative procedure for the estimate since it is based on a closed analytical formulation. PMID- 17867351 TI - A new heart rate variability analysis method by means of quantifying the variation of nonlinear dynamic patterns. AB - A new heart rate variability (HRV) analysis method, quantifying the variation of nonlinear dynamic pattern (VNDP) in heart rate series, is proposed and validated against the age stratified Fantasia database. The method is based on three processes: (1) a recurrence quantification analysis (RQA) to quantify the dynamic patterns, (2) the use of mutual information (MI) and the entropy (EN) to characterize the VNDP, and 3) linear discriminant analysis to exploit the associations within MI and EN measures. Practically, the VNDP method overcomes the nonstationarity problem and exploits the nonstationary properties in HRV analyses. Physiologically, the VNDP reflects the properties of the fundamental short-term HRV dynamic system and the external associations of the system within the autonomous nervous system (ANS). The characteristic probability density peaks portrayed by VNDP plots indicate the quantum-like heart dynamics, which may provide valuable insights into the control of the ANS. The discrimination results of the reduced pattern dynamic range due to aging, from a new perspective, display the reduction in HRV. The significantly improved discriminatory power, compared to conventional RQA analyses, shows that the VNDP analysis can practically quantify the nonstationary nonlinear dynamics for ANS assessments. PMID- 17867352 TI - Design of a wire-mesh collimator for gamma cameras. AB - This paper presents a model of a wire-mesh collimator for a gamma camera that produces images of comparable quality as those produced with the conventional multihole collimator, but has about half the weight of the multihole collimator. The gamma camera and the collimator are simulated using the MCNPX code. Two final configurations of the wire-mesh collimator are proposed, and their performance is compared with other wire-mesh collimators and with the multihole collimator, using a point source, a planar square source, and two point sources, all in water. In all cases, photons with energy 140 keV are simulated. In addition, we use the simulation of a realistic phantom of a hot tumor in a warm background to assess the performance of our collimator in conjunction with an extended source. PMID- 17867353 TI - Theoretical limits of localizing 3-D landmarks and features. AB - In this paper, we analyze the accuracy of estimating the location of 3-D landmarks and characteristic image structures. Based on nonlinear estimation theory, we study the minimal stochastic errors of the position estimate caused by noisy data. Given analytic models of the image intensities, we derive closed-form expressions of the Cramer-Rao bound for different 3-D structures such as 3-D edges, 3-D ridges, 3-D lines, 3-D boxes, and 3-D blobs. It turns out that the precision of localization depends on the noise level, the size of the region-of interest, the image contrast, the width of the intensity transitions, as well as on other parameters describing the considered image structure. The derived lower bounds can serve as benchmarks and the performance of existing algorithms can be compared with them. To give an impression of the achievable accuracy, numeric examples are presented. Moreover, by experimental investigations, we demonstrate that the derived lower bounds can be achieved by fitting parametric intensity models directly to the image data. PMID- 17867354 TI - fMRI data analysis with nonstationary noise models: a Bayesian approach. AB - The assumption of noise stationarity in the functional magnetic resonance imaging (fMRI) data analysis may lead to the loss of crucial dynamic features of the data and thus result in inaccurate activation detection. In this paper, a Bayesian approach is proposed to analyze the fMRI data with two nonstationary noise models (the time-varying variance noise model and the fractional noise model). The covariance matrices of the time-varying variance noise and the fractional noise after wavelet transform are diagonal matrices. This property is investigated under the Bayesian framework. The Bayesian estimator not only gives an accurate estimate of the weights in general linear model, but also provides posterior probability of activation in a voxel and, hence, avoids the limitations (i.e., using only hypothesis testing) in the classical methods. The performance of the proposed Bayesian methods (under the assumption of different noise models) are compared with the ordinary least squares (OLS) and the weighted least squares (WLS) methods. Results from the simulation studies validate the superiority of the proposed approach to the OLS and WLS methods considering the complex noise structures in the fMRI data. PMID- 17867355 TI - The removal of wall components in Doppler ultrasound signals by using the empirical mode decomposition algorithm. AB - Doppler ultrasound systems, used for the noninvasive detection of the vascular diseases, normally employ a high-pass filter (HPF) to remove the large, low frequency components from the vessel wall from the blood flow signal. Unfortunately, the filter also removes the low-frequency Doppler signals arising from slow-moving blood. In this paper, we propose to use a novel technique, called the empirical mode decomposition (EMD), to remove the wall components from the mixed signals. The EMD is firstly to decompose a signal into a finite and usually small number of individual components named intrinsic mode functions (IMFs). Then a strategy based on the ratios between two adjacent values of the wall-to-blood signal ratio (WBSR) has been developed to automatically identify and remove the relevant IMFs that contribute to the wall components. This method is applied to process the simulated and clinical Doppler ultrasound signals. Compared with the results based on the traditional high-pass filter, the new approach obtains improved performance for wall components removal from the mixed signals effectively and objectively, and provides us with more accurate low blood flow. PMID- 17867356 TI - Comparison of applied and induced current electrical impedance tomography. AB - Several papers on induced current electrical impedance tomography (IC-EIT) have dwelt on potential advantages of this technique over conventional EIT which uses applied current (AC-EIT). Experimental evidence that IC-EIT could surpass AC-EIT in similar imaging conditions is lacking. In this paper, we describe a system that can switch rapidly between both AC-EIT and IC-EIT. The system makes it possible to image objects in a saline-filled tank, providing data acquired in identical test conditions for comparing the performance of the two modes. The system uses eight circular coils and 16 electrodes to acquire 120 linearly independent measurements in IC-EIT and 104 in AC-EIT. Difference images were reconstructed from data acquired with both modes using the maximum a posteriori method. Spatial resolution was lower in IC-EIT images than in AC-EIT, especially in the radial direction. IC-EIT also exhibits a bias toward the center for positioning a conductivity perturbation. These results were obtained for a typical coil configuration widely used in the literature and may not be representative of alternate coil configurations. The system described in this paper provides stable experimental conditions for comparing the performance of the two EIT imaging modes and would be a valuable tool for validating new coil configurations. PMID- 17867357 TI - Real-time monitoring of cardiac regional function using fastHARP MRI and region of-interest reconstruction. AB - Cardiovascular stress test imaging assists in the diagnosis and monitoring of cardiovascular disease. The procedure can be carried out in a magnetic resonance (MR) scanner using pharmacological agents that mimic the effects of natural exercise. In order to provide real time indication of ischemia, thereby assisting in diagnosis and helping to assure patient safety, it is desirable to have real time monitoring of the myocardial regional function. This paper presents an algorithm for the real time myocardium region-of-interest reconstruction and myocardial strain computation using data acquired from a real time pulse sequence that has been previously reported. The chirp Fourier transform is used for efficient computation, enabling a real-time continuous strain map at a rate of 25 frames/s. Coupled with a real time data path from the scanner to a laptop computer, this algorithm enables real time continuous monitoring of cardiac strain and is targeted for use in the early detection and quantification of ischemia during MR stress tests. PMID- 17867358 TI - Prototype fabrication and preliminary in vitro testing of a shape memory endovascular thrombectomy device. AB - An electromechanical microactuator comprised of shape memory polymer (SMP) and shape memory nickel-titanium alloy (nitinol) was developed and used in an endovascular thrombectomy device prototype. The microactuator maintains a straight rod shape until an applied current induces electro-resistive (Joule) heating, causing the microactuator to transform into a corkscrew shape. The straight-to-corkscrew transformation geometry was chosen to permit endovascular delivery through (straight form) and retrieval of (corkscrew form) a stroke causing thrombus (blood clot) in the brain. Thermal imaging of the microactuator during actuation in air indicated that the steady-state temperature rise caused by Joule heating varied quadratically with applied current and that actuation occurred near the glass transition temperature of the SMP (86 degrees C). To demonstrate clinical application, the device was used to retrieve a blood clot in a water-filled silicone neurovascular model. Numerical modeling of the heat transfer to the surrounding blood and associated thermal effects on the adjacent artery potentially encountered during clinical use suggested that any thermal damage would likely be confined to localized areas where the microactuator was touching the artery wall. This shape memory mechanical thrombectomy device is a promising tool for treating ischemic stroke without the need for infusion of clot dissolving drugs. PMID- 17867359 TI - A multiobjective design of a patient and anaesthetist-friendly neuromuscular blockade controller. AB - During surgeries (especially in long ones), patients are subject to a substantial amount of drug dosage necessary to achieve the required neuromuscular blockade level. This paper aims at the development of a fuzzy controller that satisfies two important goals: 1) an optimization of the amount of drug (atracurium) required to induce an adequate level of relaxation and 2) a concomitant ability to explain the undertaken control decision at the level of natural language. For instance, statements of the form "Since the difference between the target and the current blockade level is near zero, a small quantity of drug infusion is currently being applied", where "near zero" and "small" are linguistic terms that are represented as fuzzy sets. In this sense, we can regard this controller as a construct that is human friendly and highly interpretable (transparent). To address the two objectives outlined above, we consider the use of a multiobjective evolutionary optimization. How the quality of the control action and the controller interpretability are formalized and captured in this optimization framework is presented. The effectiveness of the approach is demonstrated through a comprehensive suite of experiments involving 100 simulated patients (used for training) and 500 patients (forming the test set), validating the approach for application in the operating theater. PMID- 17867360 TI - Testing the immunity of active implantable medical devices to CW magnetic fields up to 1 MHz by an immersion method. AB - This paper presents a magnetic-field system and the method developed for testing the immunity of the active implantable medical devices to continuous-wave magnetic fields in the frequency range up to 1 MHz. The system is able to produce magnetic fields of 150 A/m for frequencies up to 100 kHz and strengths decreasing as 1/f between 100 kHz and 1 MHz, with uniformity of the field within +/-2.5% in the volume for tests. To simulate human tissue, the medical device, together with its leads, is placed on a plastic grid in a saline tank that is introduced in the magnetic field of the induction coil. This paper offers an alternative for the injection voltage methods provided in the actual standards for assessing the protection of the implantable medical devices from the effects of the magnetic fields up to 1 MHz. This paper presents the equipment and signals used, the test procedure, and results from the preliminary tests performed at the Food and Drug Administration-Center for Devices and Radiological Health on implantable pacemakers and neurostimulators. The new system and test method are useful for the EMC research on the implantable medical devices. PMID- 17867362 TI - Robotic platform for human gait analysis. AB - A hydraulically actuated platform with 4-degrees of freedom (4-DOF) was designed to be able to apply velocity- or acceleration-controlled floor surface perturbations to freely walking human subjects. The apparatus was required to provide velocity-controlled translational perturbations over the floor surface, rotational perturbations about the ankle joint, and acceleration-controlled vertical translational perturbations. The apparatus was physically constructed, and tested by both measurements of dynamics and repeatability. Crossover of movement from one DOF to another was shown to be less than 1 mm or 0.5 degrees for all desired perturbations. Repeated perturbations were nearly identical with a standard deviation of less than 0.2 mm over translational axes. The application of the platform to human gait research was demonstrated with a protocol of midstance phase perturbations (n=8). For this, the platform controller was programmed to randomly select one out of three conditions: (1) no movement (control); (2) upward perturbation of 0.8 g, 50 mm, 300 ms after heel contact; (3) downward perturbation of 0.8 g, 50 mm, 300 ms after heel contact. In total, 90 trials (3 conditions x 30 repetitions) were recorded for each subject. By singling out the SOL EMG and normalizing and averaging over the subject population, it was shown that the upward and downward perturbations elicited at least two distinctive stereotypical reflex responses in the ankle extensors, opposite in sign. All subjects reported comfort with the apparatus and nobody fell. PMID- 17867361 TI - Design of patient-specific gait modifications for knee osteoarthritis rehabilitation. AB - Abstract-Gait modification is a nonsurgical approach for reducing the external knee adduction torque in patients with knee osteoarthritis (OA). The magnitude of the first adduction torque peak in particular is strongly associated with knee OA progression. While toeing out has been shown to reduce the second peak, no clinically realistic gait modifications have been identified that effectively reduce both peaks simultaneously. This study predicts novel patient-specific gait modifications that achieve this goal without changing the foot path. The modified gait motion was designed for a single patient with knee OA using dynamic optimization of a patient-specific, full-body gait model. The cost function minimized the knee adduction torque subject to constraints limiting how much the new gait motion could deviate from the patient's normal gait motion. The optimizations predicted a "medial-thrust" gait pattern that reduced the first adduction torque peak between 32% and 54% and the second peak between 34% and 56%. The new motion involved three synergistic kinematic changes: slightly decreased pelvis obliquity, slightly increased leg flexion, and slightly increased pelvis axial rotation. After gait retraining, the patient achieved adduction torque reductions of 39% to 50% in the first peak and 37% to 55% in the second one. These reductions are comparable to those reported after high tibial osteotomy surgery. The associated kinematic changes were consistent with the predictions except for pelvis obliquity, which showed little change. This study demonstrates that it is feasible to design novel patient-specific gait modifications with potential clinical benefit using dynamic optimization of patient-specific, full-body gait models. Further investigation is needed to assess the extent to which similar gait modifications may be effective for other patients with knee OA. PMID- 17867363 TI - Fluoroscopic bone fragment tracking for surgical navigation in femur fracture reduction by incorporating optical tracking of hip joint rotation center. AB - A new method for fluoroscopic tracking of a proximal bone fragment in femoral fracture reduction is presented. The proposed method combines 2-D and 3-D image registration from single-view fluoroscopy with tracking of the head center position of the proximal femoral fragment to improve the accuracy of fluoroscopic registration without the need for repeated manual adjustment of the C-arm as required in stereo-view registrations. Kinematic knowledge of the hip joint, which has a positional correspondence with the femoral head center and the pelvis acetabular center, allows the position of the femoral fragment to be determined from pelvis tracking. The stability of the proposed method with respect to fluoroscopic image noise and the desired continuity of the fracture reduction operation is demonstrated, and the accuracy of tracking is shown to be superior to that achievable by single-view image registration, particularly in depth translation. PMID- 17867364 TI - Redefining performance evaluation tools for real-time QRS complex classification systems. AB - In a heartbeat classification procedure, the detection of QRS complex waveforms is necessary. In many studies, this heartbeat extraction function is not considered: the inputs of the classifier are assumed to be correctly identified. This communication aims to redefine classical performance evaluation tools in entire QRS complex classification systems and to evaluate the effects induced by QRS detection errors on the performance of heartbeat classification processing (normal versus abnormal). Performance statistics are given and discussed considering the MIT/BIH database records that are replayed on a real-time classification system composed of the classical detector proposed by Hamilton and Tompkins, followed by a neural-network classifier. This study shows that a classification accuracy of 96.72% falls to 94.90% when a drop of 1.78% error rate is introduced in the detector quality. This corresponds to an increase of about 50% bad classifications. PMID- 17867365 TI - Phase resetting in one-dimensional model of the sinoatrial node. AB - In this paper, we use a one-dimensional model of the rabbit sinoatrial node (SAN), and we investigate the response of the model to hyperpolarizing and depolarizing stimulus. Depending on the stimulus timing, either a delay or an advance in the occurrence of next action potential is produced. This resetting behavior of the model is quantified in terms of phase transition curves (PTCs) for short electrical current pulses of varying amplitude which span the whole period. The main focus of this paper is to compare the dynamic properties of the spatially extended system and the single cell model. The detailed analysis of the results provides new insights in the understanding of the transition from the theoretical single cell models to the spatially extended systems. PMID- 17867366 TI - A hybrid classifier fusion approach for motor unit potential classification during EMG signal decomposition. AB - In this paper, we propose a hybrid classifier fusion scheme for motor unit potential classification during electromyographic (EMG) signal decomposition. The scheme uses an aggregator module consisting of two stages of classifier fusion: the first at the abstract level using class labels and the second at the measurement level using confidence values. Performance of the developed system was evaluated using one set of real signals and two sets of simulated signals and was compared with the performance of the constituent base classifiers and the performance of a one-stage classifier fusion approach. Across the EMG signal data sets used and relative to the performance of base classifiers, the hybrid approach had better average classification performance overall. For the set of simulated signals of varying intensity, the hybrid classifier fusion system had on average an improved correct classification rate (CCr) (6.1%) and reduced error rate (Er) (0.4%). For the set of simulated signals of varying amounts of shape and/or firing pattern variability, the hybrid classifier fusion system had on average an improved CCr (6.2%) and reduced Er (0.9%). For real signals, the hybrid classifier fusion system had on average an improved CCr (7.5%) and reduced Er (1.7%). PMID- 17867367 TI - A shape memory polymer dialysis needle adapter for the reduction of hemodynamic stress within arteriovenous grafts. AB - A deployable, shape memory polymer adapter is investigated for reducing the hemodynamic stress caused by dialysis needle flow impingement within an arteriovenous graft. Computational fluid dynamics simulations of dialysis sessions with and without the adapter demonstrate that the adapter provides a significant decrease in the wall shear stress. Preliminary in vitro flow visualization measurements are made within a graft model following delivery and actuation of a prototype shape memory polymer adapter. Both the simulations and the qualitative flow visualization measurements demonstrate that the adapter reduces the severity of the dialysis needle flow impingement on the vascular access graft. PMID- 17867368 TI - Origin of the radio frequency pulse artifact in simultaneous EEG-fMRI recording: rectification at the carbon-metal interface. AB - Simultaneous electroencephalograph-functional magnetic resonance imaging (EEG fMRI) recording has become an important tool for investigating spatiotemporal properties of brain events, such as epilepsy, evoked brain responses, and changes in brain rhythms. Reduction of noise in EEG signals during fMRI recording is crucial for acquiring high-quality EEG-fMRI data. The main source of the noise includes the gradient artifact, the radio frequency (RF) pulse artifact, and the cardiac pulse artifact. Since the RF pulse artifact is relatively small in amplitude, little attention has been paid to this artifact, and its origin is not well understood. However, the amplitude of the RF pulse artifact fluctuates randomly even if a very high EEG sampling rate is used, making it more salient than the gradient artifact after postprocessing for noise removal. In this paper, we investigate the cause of the RF pulse artifact in EEG systems that use carbon wires. PMID- 17867369 TI - Nutritional support for the infant's immune system. AB - Newborn babies possess a functional but immature immune system as a defense against a world teeming with microorganisms. Breast milk contains a number of biological, active compounds that support the infant's immune system. These include secretory immunoglobulin A (IgA), which confers specific protection against enteric pathogens, as well as numerous other immunological, active ingredients. A number of these ingredients can be used as supplements for infant formulas based on cow's milk. Here, the strength of evidence regarding the immune stimulating effects of selected minerals, vitamins, fatty acids, pre- and probiotics, and nucleotides is reviewed. An assessment of how these ingredients are used in infant-formula products currently available on the market is also presented. PMID- 17867370 TI - Mechanisms and effects of green tea on cardiovascular health. AB - Green tea, rich in antioxidant and anti-inflammatory catechins, especially epigallocatechin gallate (EGCG), has been shown to reduce surrogate markers of atherosclerosis and lipid peroxidation, particularly LDL oxidation and malondialdehyde concentrations, in several in vitro, animal, and limited clinical studies. Epidemiological observations in Southeast Asian countries indicate an inverse correlation exists between habitual consumption of green tea beverages and the incidence of cardiovascular events. A few short-term clinical studies have reported its effects in attenuating biomarkers of oxidative stress and inflammation among smokers, and an ability to decrease postprandial lipemia in hypercholesterolemic subjects has also been suggested. However, further investigations are needed to confirm the potential role of green tea beverages and the safety of green tea supplements in reducing body fat, as well as other biomarkers of cardiovascular disease risks. PMID- 17867371 TI - Nonalcoholic fatty liver disease: pathogenesis, identification, progression, and management. AB - Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases in the absence of significant alcohol consumption, and its incidence is paralleling the increasing numbers of overweight and obese individuals worldwide. This review discusses the pathogenesis of NAFLD, including the roles potentially played by specific adipokines, such as TNF-alpha, leptin, and adiponectin. Clinical features, diagnosis, and potential methods of management are also addressed to assist practitioners with the management of this growing population of patients. PMID- 17867372 TI - Identification of a membrane receptor for retinol-binding protein functioning in the cellular uptake of retinol. AB - Retinol-binding protein (RBP) is the transport protein that carries retinol in the circulation from the liver to its target tissues. The existence of a cell surface receptor on the target cells, which mediates the uptake of retinol from RBP, has been known since 1975. Recently, it was identified as an integral transmembrane protein named STRA6 that is inducible by retinoic acid in certain cancer cells. The receptor was found to be highly specific for RBP, with high affinity, and to be localized in all tissues known to require retinol for their function, particularly the pigment epithelium of the eye. PMID- 17867373 TI - Vitamin D and cancer: current dilemmas and future needs. PMID- 17867374 TI - The 'cocaine blues' and other problems in epidemiologic studies of vitamin D and cancer. PMID- 17867375 TI - Strengths and limitations of current epidemiologic studies: vitamin D as a modifier of colon and prostate cancer risk. PMID- 17867376 TI - Epidemiological studies of vitamin D and breast cancer. PMID- 17867377 TI - Sun exposure measurements in populations. PMID- 17867378 TI - Assessment of circulating 25(OH)D and 1,25(OH)2D: emergence as clinically important diagnostic tools. PMID- 17867379 TI - What is the dose-response relationship between vitamin D and cancer risk? PMID- 17867380 TI - What are the frequency, distribution, and functional effects of vitamin D receptor polymorphisms as related to cancer risk? PMID- 17867381 TI - Vitamin D receptor gene (VDR) associations with cancer. PMID- 17867382 TI - Can diet and/or sunlight modify the relationship between vitamin D receptor polymorphisms and prostate cancer risk? PMID- 17867383 TI - Extrarenal vitamin D hydroxylase expression and activity in normal and malignant cells: modification of expression by epigenetic mechanisms and dietary substances. PMID- 17867384 TI - Vitamin D inhibition of the prostaglandin pathway as therapy for prostate cancer. PMID- 17867385 TI - Interactions between vitamin D and androgen receptor signaling in prostate cancer cells. PMID- 17867386 TI - Vitamin D and the regulation of Wnt/beta-catenin signaling and innate immunity in colorectal cancer. PMID- 17867388 TI - Do body fat and exercise modulate vitamin D status? PMID- 17867387 TI - Potentiation of the growth-inhibitory effects of vitamin D in prostate cancer by genistein. PMID- 17867389 TI - What have genomic and proteomic approaches told us about vitamin D and cancer? PMID- 17867390 TI - Calcium, vitamin D and the vitamin D receptor: impact on prostate and breast cancer in preclinical models. PMID- 17867391 TI - Molecular targets of calcium and vitamin D in mouse genetic models of intestinal cancer. PMID- 17867392 TI - A conceptual model of parental behavior change following a child's dental general anesthesia procedure. AB - PURPOSE: The purpose of this study was to investigate parents' challenges to long term maintenance of healthy behaviors following their child's dental general anesthesia (GA). METHODS: Twenty-six in-depth interviews were conducted with parents of children younger than 6 years of age who had dental treatment under GA. The interviews were scheduled at various time periods following the surgery. Compared were the responses of: (1) "relapse" families, whose child had new cavities at the 6-month recall; and (2) "no relapse" families, who were caries free at recoil. A grounded theory approach to data analysis was used. RESULTS: "Relapse" parents: (1) valued baby teeth differently; (2) perceived their child to be less susceptible to new cavities; and (3) expressed lower self-efficacy for controlling their child's oral health compared to "no relapse" parents. They also appeared to be: (1) in earlier stages of change; (2) less receptive to advice from others, including professionals; and (3) more permissive regarding their child's desires. "Relapse" parents did not seem to have any immediate plans to change their "home-care" behaviors. CONCLUSION: GA did not appear to affect long term preventive behaviors for all parents. Readiness to change seemed to be an important predictor of whether parents adopted and maintained preventive behaviors to improve their child's oral health. PMID- 17867393 TI - Pediatric oral health knowledge of African American and Hispanic of Mexican origin expectant mothers. AB - PURPOSE: This study assessed the impact of a lecture on children's oral health knowledge of pregnant women from vulnerable African American (AA) and Hispanic of Mexican origin (HM) populations utilizing the same urban community health center prenatal education program. METHODS: Participants heard one 45-minute lecture in English or Spanish on children's oral health, and completed a survey (English or Spanish) before and after the lecture. RESULTS: Seven sessions provided 60 participants: (a) 30 AA; and (b) 30 HM. These two groups differed on: (1) educational attainment; (2) preferred language; (3) country of origin; and (4) baseline scores. They were similar in: (1) age; (2) frequency of first mothers; and (3) final scores. Oral health knowledge significantly rose from baseline to the end of the lecture (ANOVA, P < .001). Educational attainment was associated with HM baseline scores (P = .04), whereas age was associated with AA final scores (P = .01). CONCLUSIONS: An oral health lecture within a prenatal program improved oral health knowledge for African American and Hispanic of Mexican origin pregnant women, though associated factors varied between the two groups. Further study is needed to explore long-term knowledge retention and effect on the future babies' oral health. PMID- 17867394 TI - Medicaid participation by private dentists in Alabama. AB - OBJECTIVE: The objective of this study was to examine the relationship between private dentists' attitudes toward Medicaid and Medicaid patients and their extent of Medicaid participation. METHODS: A survey was mailed to all Medicaid dentists in Alabama in 2003 (N = 518). Descriptive statistics were calculated, and multiple regression models were tested. The "dentists' extent of participation" was a measure of the percentage of Medicaid patients seen in one month. Independent variables included dentists' personal and practice characteristics; market area characteristics; and dentists' attitudes toward Medicaid and Medicaid patients. RESULTS: A total of 277 (54%) surveys was returned. Non-Caucasian dentists in group practice had a higher mean of extent of Medicaid participation than Caucasian dentists in solo practice. Moreover, compared to privately insured families, dentists had significantly higher mean of extent of Medicaid participation if they perceived Medicaid reimbursement as generous; payments being processed faster; and families as not acceptable to non Medicaid families in the practice. CONCLUSIONS: Dentists' perceptions of Medicaid policies, such as generosity of payment and speed of processing payment, are important to ensure continued provider participation in Medicaid. Strategies to improve dentists' participation in Medicaid must be multifaceted to increase access to dental services for Medicaid children. PMID- 17867395 TI - An in vitro comparison of marginal microleakage of alternative restorative treatment and conventional glass ionomer restorations in extracted permanent molars. AB - PURPOSE: The objective of this study was to compare the marginal leakage of cervical restorations made using alternative restorative treatment (ART) and conventional glass ionomer restorations. METHODS: Sixteen permanent maxillary and mandibular first and second molars extracted for periodontal reasons with Class V carious dentin on the buccal surfaces were prepared using ART while a second set of 29 noncarious molars had Class V preparations made with a high-speed handpiece. The occlusal margin was located in the enamel, and the gingival margin was located in the dentin/cementum. All teeth were restored with glass ionomer cement (GIC). The teeth were thermally stressed for 300 cycles and stained with methylene blue. Samples were sectioned and evaluated for microleakage. RESULTS: One-way analysis of variance on ranks revealed no significant difference in leakage at both the dentin and enamel margins between the conventional and ART groups. The microleakage at the dentin margin, however, was significantly greater (P < .001) than at the enamel margins in the conventional group. CONCLUSION: Alternative restorative treatment with GIC provides enamel and dentin margins that show comparable marginal leakage to conventionally restored permanent teeth. For the conventional restorations, leakage at the dentin margins occurs to a significantly higher extent than at the enamel margins. PMID- 17867396 TI - Effect of preparation technique, fissure morphology, and material characteristics on the in vitro margin permeability and penetrability of pit and fissure sealants. AB - PURPOSE: The purpose of this study was to evaluate the effect of material characteristics, preparation techniques, and fissure morphology on the microleakage and penetrability of pit and fissure sealants. METHODS: Sealants used in the study included: (1) Aegis; (2) Conseal f; (3) Admira Seal; (4) Triage; and (5) Delton Opaque. A total of 100 extracted permanent molars were randomly assigned to 10 groups that combined the materials and preparation technique (pumice prophylaxis and air abrasion). Following sealant placement, the specimens were: (1) subjected to thermal-cycling and dye immersion; (2) invested in acrylic; (3) sectioned for microscopic examination; and (4) assessed for dye penetration (microleakage) and penetrability. RESULTS: Significant differences in microleakage were seen. Aegis using pumice-prophylaxis surface pretreatment showed significantly less leakage than the other groups. Significant differences were also exhibited between groups seen regarding sealant penetrability, with Delton and Triage (pumice prophylaxis) revealing the greatest values. Fissure morphology was not a significant factor regarding microleakage. Morphology did significantly impact sealant penetrability, however, with u-type fissures displaying the greatest values. No correlation was found between the extent of microleakage and sealant penetrability. CONCLUSION: Material characteristics and fissure morphology were significant factors regarding sealant success, while surface preparation did not play an important role in sealant microleakage or fissure penetrability. PMID- 17867397 TI - Dental management of a child with congenital sideroblastic anemia: a case report. AB - The sideroblastic anemias comprise a heterogeneous group of acquired and congenital disorders which that have in common: (1) anemia; (2) the presence of ring sideroblasts in the bone marrow; and (3) impaired heme biosynthesis. Elevation in iron levels is secondary to a deficiency in mitochondrial physiology. Patients exhibit mild to moderate hemolysis due to peripheral red blood cell destruction, and often require regular blood transfusions. The purpose of this case report was to describe the dental management of a child with congenital sideroblastic anemia--a rare hematologic disorder--and to emphasize how important it is for pediatric dentists to be cognizant of a patient's hematologic profile before attempting to perform any dental procedure. The timing of the patient's transfusions regarding the scheduling of dental care is crucial for successful management and anticipation of possible complications. Preventive dentistry should be a hallmark of dental management for these children. PMID- 17867398 TI - A new threat to adolescent oral health: the grill. AB - The wearing of dental "grills" in the mouths of children, adolescents, and adults is a problematic fad currently facing the dental community. A grill is a gold, platinum, or other metal and often jewel-encrusted encasement for the dentition. The grill can be easily placed over the existing teeth and is fabricated by simply obtaining an impression of an area of a person's mouth over which a grill is desired. The purpose of this case study was to report the oral and dental manifestations of a case in which a grill was worn by an uninformed adolescent consumer. A 16-year-old African American male was clinically evaluated on a routine recall appointment in this case. He had evidence of new rampant anterior decay in an oral cavity that had previously been caries-free on all earlier regular hygiene visits. A strong factor contributing to decoy was the purchase and regular wear of a grill from a neighborhood jewelry store. This case report was conducted to alert dental professionals, more specifically pediatric dentists, about the increased popularity of the grill and to the detrimental affects that it can have upon the unhygienic dentition. PMID- 17867399 TI - Oral manifestations of a possible new periodic fever syndrome. AB - Periodic fever syndrome is composed of a group of disorders that present with recurrent predictable episodes of fever, which may be accompanied by: (1) lymphadenopathy; (2) malaise; (3) gastrointestinal disturbances; (4) arthrolgia; (5) stomatitis; and (6) skin lesions. These signs and symptoms occur in distinct intervals every 4 to 6 weeks and resolve without any residual effect, and the patient remains healthy between attacks. The evaluation must exclude: (1) infections; (2) neoplasms; and (3) autoimmune conditions. The purpose of this paper is to report the case of a 41/2- year-old white female who presented with a history of periodic fevers accompanied by: (1) joint pain; (2) skin lesions; (3) rhinitis; (4) vomiting; (5) diarrhea; and (6) an unusual asymptomatic, marked, fiery red glossitis with features evolving to resemble geographic tongue and then resolving completely between episodes. This may represent the first known reported case in the literature of a periodic fever syndrome presenting with such unusual recurring oral findings. PMID- 17867400 TI - Clinical tips for the Halterman appliance. AB - Ectopic eruption of permanent first molars occurs infrequently and causes some resorption of the adjacent primary second molar. The primary second molar can be used as an anchor tooth for the Halterman appliance to disimpact the permanent first molar, provided root resorption is not extreme. A modification of the Halterman appliance is a reverse band and loop appliance with a bonded button on the permanent molar and chain elastic for disimpaction. The purpose of this report was to suggest tips regarding placement and clinical management of this modified Halterman appliance design. PMID- 17867401 TI - Clinical solutions for developmental defects of enamel and dentin in children. AB - Developmental defects of enamel (DDE) are frequently observed in pediatric dental patients. Proper diagnosis may improve the clinician's dental care. The purpose of this article is to present the clinical management of some common dental defects: (1) hypoplasia; (2) diffuse and demarcated opacities; (3) fluorosis; (4) amelogenesis imperfecto (Al); and (5) dentinogenesis imperfecto (DI). The comprehensive management of DDE in children and adolescents should include: (1) active follow-up and observation involving oral hygiene instructions; and (2) dietary consultation. Preventive care should be individually tailored according to the patient's risk-assessment analysis. The treatment of DDE involves an approach that includes several disciplines, including: (1) pediatric dentistry; (2) orthodontics; (3) perioprosthetics; and (4) psychology. A close follow-up is essential to achieve long-term success. PMID- 17867402 TI - The effectiveness of a novel infant tooth wipe in high caries-risk babies 8 to15 months old. AB - PURPOSE: The purpose of this study was to assess baby and parental satisfaction and plaque-removal efficacy of a novel infant tooth wipe (Spiffies) in high caries-risk babies. METHODS: Thirty-five healthy and caries-free infants were selected. Babies had never had their teeth cleaned and no primary molars were yet present. Subjects were identified with the risk factor of nightly feeding behaviors. Pre- and postcleaning oral hygiene plaque measurements were recorded and then analyzed by a blinded examiner. A manual toothbrush (Ultra Kids) was used as the control method. Infants' caregivers used their randomly assigned cleaning method without instruction. Babies returned to the clinic after a 48- to 72-hour washout period, and the procedures were repeated before and after use of the alternate method. Parental satisfaction and baby-perceived acceptance were evaluated by a questionnaire and were analyzed at the time of the visit and at bedtime. RESULTS: Both the infant tooth wipe and conventional brushing significantly reduced plaque levels (P < .001). Parents were more satisfied with the wipes when compared to toothbrushing, particularly after nightly feeding habits (P < .001). Similarly, infant's acceptance was higher with the wipes at daytime and significantly higher at night-time (P = .002). CONCLUSIONS: The Novel novel Infant infant Tooth tooth Wipe wipe provides an effective method of plaque removal before the eruption of primary molars. PMID- 17867403 TI - IRBs and the private office. PMID- 17867404 TI - The Bagdad boil deploys to the United States. PMID- 17867405 TI - Pediatric gastroenterology. PMID- 17867406 TI - Women's preventive health service preferences in the Rhode Island Hospital Emergency Department. PMID- 17867407 TI - Bach, botox, and butterflies: toward an awareness of musician's dystonia. PMID- 17867408 TI - Exercise-limiting symptoms in children. AB - Transient exercise-related symptoms are common in children and adolescents and only rarely reflect underlying cardiac and pulmonary disease processes. Most symptoms occurring during exercise reflect changes related to normal exercise physiology, changes in level of competition, and musculoskeletal and developmental factors. A rational approach to screening for potentially life threatening cardiac conditions and exercise-induced bronchospasm is important to minimize the risk of misdiagnosis and to keep the young athlete active. PMID- 17867409 TI - Use of neuroimaging in the workup of headache. PMID- 17867410 TI - The performance of Rhode Island's commercial health plans, 2005. PMID- 17867411 TI - Elder abuse and mistreatment. PMID- 17867412 TI - Dedicated reader's kind words. PMID- 17867413 TI - Third-shift stereotype? PMID- 17867414 TI - Ethics: a code for the laboratory. AB - The subject of ethics has become relevant once again since the 2004 expose of fraudulent laboratory practices involving HIV and hepatitis testing at the Maryland General Hospital. After congressional hearings into accrediting organizations entrusted to assure healthcare standards and patient safety, which had inspected Maryland General, vital changes were made--and laboratories are now subject to unannounced inspections. Here, we present a quondam cover story (June 1995) with a companion article (March 1998) that prove the subject of ethics never goes out of fashion. PMID- 17867415 TI - Ethos and the laboratory leader. PMID- 17867416 TI - Defining accuracy and precision. PMID- 17867417 TI - Health and safety issues in lab design. PMID- 17867418 TI - A conversation about changing life goals. PMID- 17867419 TI - Gossip in the laboratory. PMID- 17867420 TI - State and federal legislation in personalized medicine. PMID- 17867421 TI - Monkey business. PMID- 17867422 TI - It's okay: they've found the money. PMID- 17867423 TI - Practitioner influence. PMID- 17867424 TI - Nil by mouth: a misleading statement. AB - Preoperative fasting is universally accepted as a beneficial practice to reduce the risk of pulmonary aspiration of gastric contents during the induction of general anaesthesia. What is less clear for many junior doctors and nurses is the administration of oral medication during the fasting period. This study aims to highlight the subjective understanding of the statement, 'nil by mouth' with regard to drug administration. PMID- 17867425 TI - Plagiarism: understanding and management. AB - An epidemic of plagiarism is sweeping the world. A study carried out in the US suggested that 80% of college students admit to cheating at least once (Ashworth et al 1997). Alternative evidence from an American education and software company, Plagiarism.org, reported that 36% of undergraduates plagiarise written material and that 90% of students believe that cheaters are never caught or disciplined (Plagiarism.org 2005). Closer to home, research carried out in the UK by Clare (1996) suggested that 50% of students copy work and invent data. More recently the Plagiarism Advisory Service, based at Northumbria University, reported that 25% of students plagiarise, while lecturers only detect plagiarism 3% of the time (Plagiarism Advisory Service 2006). PMID- 17867426 TI - Ensuring safe and effective practice: fitness for practice at the point of registration. AB - The Nursing and Midwifery Council (NMC) has been reviewing its standards for the preparation of teachers and considering issues related to fitness for practice at the point of registration. This has resulted in new standards to support learning and assessment in practice (NMC 2006a). The standards have attempted to address learning in an interprofessional practice environment, taking account of the different professionals involved in supporting and assessing learning, while maintaining the integrity of particular professions. PMID- 17867427 TI - Pneumatic tourniquet use in the perioperative environment. AB - Pneumatic tourniquets are routinely used in operating theatres worldwide. Generally, tourniquets are viewed as a relatively safe instrument with minimal complications. Nevertheless, Klenerman (2003) and Golder et al (2000) both suggest that caution should be exercised in tourniquet use. Furthermore Phillips (2004, p532) claims that, 'a tourniquet is dangerous to apply, to leave on and to remove'. This article will inform perioperative practitioners of the current research pertaining to the routine procedure of using pneumatic tourniquets to achieve a bloodless surgical field. PMID- 17867428 TI - The Kolff artificial kidney. AB - Nowadays renal dialysis, with its sleek, compact machinery, is a routine, somewhat taken for granted procedure in our hospitals. The development of this life-saving apparatus, initiated by a young Dutch physician during the Nazi occupation of his country, is a fascinating story. PMID- 17867429 TI - Diminution of hypertriglyceridemia-induced pressor effect under hyperinsulinemic condition in normal and fructose-induced insulin resistant rats. AB - This study aimed to evaluate the effect of hyperinsulinemia on hypertriglyceridemia-induced pressor response in normal and fructose-induced insulin resistant rats. The rats were divided into six groups of eight rats and were fed a fructose-enriched diet (FINs, F(INS+TG)) or a regular chow diet (C, C(TG), C(INS), C(INS+TG)) for 8 wks. The acute experiment was conducted at the end of wk 8 and consisted of a 30-min basal period and followed by a 120-min test period. After the basal period, somatostatin (1.3 microg/kg/ min) combined with regular insulin (0.6 or 4 mU/kg/min) and variable glucose infusion were given to clamp euglycemia and euinsulinemia in C and C(TG) or euglycemia and hyperinsulinemia in CINs, C(INS+TG), F(INS) and F(INS+TG). During test period, lipofundin (a triglyceride emulsion) was infused into CTG, C(INS+TG), F(INS+TG) and saline instead was infused into C, C(INS), FINS. Plasma insulin and triglyceride levels were significantly higher in fructose-fed rats than in normal rats. During the test period, the lipofundin infusion (1.2 ml/kg/hr) increased plasma triglyceride levels by 368 +/- 39, 351 +/- 71 and 489 +/- 38 mg/dl compared with their baseline levels in lipid-infused groups. During the test period, low-dose insulin infusion kept plasma insulin at basal levels in C and C(TG) and high-dose insulin infusion increased plasma insulin levels about 6 times the baseline insulin level in C. Glucose infusion rate (GIR) was significantly higher in rats with high insulin infusion than those with low insulin infusion. The increase in GIR was lower in fructose-fed groups than in control groups under similar hyperinsulinemia. Rats with or without lipofundin infusion did not alter GIR during the test period. The present results demonstrated that hypertriglyceridemia-induced pressor response was diminished under hyperinsulinemic condition in both normal and fructose-induced insulin resistant rats. PMID- 17867430 TI - Multiple-band trigger features of midbrain auditory neurons revealed in composite spectro-temporal receptive fields. AB - Receptive fields of single units in the auditory midbrain of anesthetized rats were studied using random FM-tone stimuli of narrow frequency-ranges. Peri-spike averaging of the modulating waveform first produced a spectro-temporal receptive field (STRF). Combining STRFs obtained from the same unit at different frequency regions generated a composite receptive field covering a wider frequency range of 2 to 3 octaves. About 20% of the composite STRFs (26/122) showed a pattern of multiple-bands which were not clear in the non-composite maps. Multiple-bands in a given composite map were often oriented in the same direction (representing upward or downward FM ramp) separated at rather regular frequency intervals. They reflect multiple FM trigger features in the stimulus rather than repetitive firing to a single trigger feature. Results showed that the subcortical auditory pathways are capable of detecting multiple FM features and such sensitivity could be useful in detecting multiple-harmonic FM bands present in the vocalization sounds. PMID- 17867431 TI - Aging effects on the habitual expression of HSP70 mRNA in the hippocampus of rats. AB - Heat shock proteins are induced by stressful stimuli and have been shown to protect cells and organs from such stresses both in vitro and in vivo. This study examined the regulation of HSP70 mRNA expression and detected the effect of aging on RNA expression in hippocampus of rats. The stress models were built by using forced-swimming in 25 degrees C and 4 degrees C water, respectively. Two groups of male rats, 2-month-old and 16-month-old, respectively, were randomly divided into three subgroups: acute stress (AS) model, chronic habituation stress (CHS) model and chronic dishabituation stress (CDS) model. Observation of exploratory behavior in an open-field (OF) test indicated stress levels. The expression of HSP70 mRNA in hippocampus was measured by RT-PCR after 0, 30, 60, 180, and 360 min of stress, respectively. Results showed that the number of quadrant crossing in both aged CHS and young CHS groups decreased gradually with the process of stress, reflecting an adaptation to the stress condition. Repeated swimming in warm water resulted in habitual expression of HSP70 mRNA in both young and aged CHS group, indicating an adaptation to the stress. The RNA expression of young CHS group was significantly stronger than that of the aged CHS group at 30, 60, 180, and 360 min after stress (P < 0.05). Meanwhile, in an intensive stress level in which the rats swam in 4 degrees C water, a high expression level of HSP70 mRNA was achieved in CDS groups, producing a dishabituation that proved the habitual expression from the other side. These results showed that senescence dramatically affected both exploratory behavior and HSP70 mRNA expression in rats' hippocampus. The results also suggested that chronic stress could lead to the habituational expression of HSP70 mRNA, but high intensive stress could reverse the habituational state and lead to the dishabituational expression. Moreover, the duration of stimuli is one of the important factors that affect the level of HSP70 mRNA expression. PMID- 17867433 TI - Hypoxia/Reoxygenation induces nitric oxide and TNF-alpha release from cultured microglia but not astrocytes of the rat. AB - Hypoxia/reoxygenation (H/R) elicits neuronal cell injury and glial cell activation within the central nervous system (CNS). Neuroinflammation is a process that primarily results from the acute or chronic activation of glial cells. This overactive state of glial cells results in the increased release of nitric oxide (NO) and/or tumor necrosis factor alpha (TNF-alpha), a process which can lead to neuronal damage or death. In this study, we found that hypoxia for eight or twelve hours (h) followed by 24 h reoxygenation (H8/ R24 or H12/R24) induced NO production and TNF-alpha release from cultures of enriched microglial or mixed glial cells. However, microglial cells could not survive longer periods of hypoxia (> or = 12 h) in microglia-enriched culture. While astrocytes retained a 95% viability following longer periods of H/R in astrocyte-enriched cultures, they did not produce any significant quantities of NO and TNF-alpha. Reoxygenation for prolonged periods (three and five days) following H24 resulted in progressively greater increases in NO production (about two-fold greater level in hypoxia as compared to normoxic conditions) accompanied by relatively less increases in TNF-alpha release in mixed glial cell cultures. Our data indicate that inflammatory mediators such as NO and TNF-alpha are released from glia enriched mix culture in response to H/R. While microglial cells are more vulnerable than astrocytes during H/R, they survive longer in the presence of astrocyte and are the major cell type producing NO and TNF-alpha. Furthermore, the TNF-alpha release precedes NO production in response to a prolonged duration of reoxygenation following hypoxia for 24 h. PMID- 17867432 TI - Antiplatelet activity of caffeic acid phenethyl ester is mediated through a cyclic GMP-dependent pathway in human platelets. AB - The aim of this study was to examine the inhibitory mechanisms of caffeic acid phenethyl ester (CAPE), which is derived from the propolis of honeybee, in platelet activation. In this study, CAPE (15 and 25 microM) markedly inhibited platelet aggregation stimulated by collagen (2 microg/ml). CAPE (15 and 25 microM) increased cyclic GMP level, and cyclic GMP-induced vasodilator-stimulated phosphoprotein (VASP) Ser157 phosphorylation, but did not increase cyclic AMP in washed human platelets. Rapid phosphorylation of a platelet protein of Mw. 47,000 (P47), a marker of protein kinase C activation, was triggered by phorbol-12, 13 dibutyrate (150 nM). This phosphorylation was markedly inhibited by CAPE (15 and 25 microM). The present study reports a novel and potent antiplatelet agent, CAPE, which involved in the following inhibitory pathways: CAPE increases cyclic GMP/VASP Ser157 phosphorylation, and subsequently inhibits protein kinase C activity, resulting in inhibition of P47 phosphorylation, which ultimately inhibits platelet aggregation. These results strongly indicate that CAPE appears to represent a novel and potent antiplatelet agent for treatment of arterial thromboembolism. PMID- 17867434 TI - Simple anthropometric indices in relation to cardiovascular risk factors in Chinese type 2 diabetic patients. AB - To determine which is the best anthropometric index among body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and waist to height ratio (WHtR) in type 2 diabetic patients, we examined the relationship between these indices and cardiovascular risk factors using partial correlation analysis, chi square test, logistic regression analysis and Receiver Operator Characteristic (ROC) curves. Partial correlation analysis showed that among the 4 obesity indices, WHtR had the highest r values for all the cardiovascular risk factors in both sexes, followed by WC. Chi-square analysis which revealed that an increased WHtR was more strongly associated with hypertension, hypertriglyceridemia (high TG) and low high-density lipoprotein cholesterol (HDL-C) than the other indices. Logistic regression analysis showed that, after controlling for age, the hypertension, high TG and low HDL-C odds ratios of WHtR > or = 0.5 were 2.56 (95% CI: 1.24, 5.29), 2.87 (95% CI: 1.43, 5.78), 2.59 (95% CI: 1.03, 6.59) in men and 3.75 (95% CI: 1.75, 8.05), 3.21 (95% CI: 1.52, 6.79), 3.62 (95% CI: 1.43, 9.21) in women, respectively. In ROC analysis, the areas under curve of WHtR were the largest for at least one risk factor in both men and women. These results indicated that WHtR had a higher correlation with cardiovascular risk factors than WC, WHR or BMI in newly diagnosed type 2 diabetes. We proposed the measurement of WHtR as a screening tool for cardiovascular risk factors in this population. PMID- 17867435 TI - Effects of benzo(a)pyrene and ethanol on oxidative stress of brain, lung tissues and lung morphology in rats. AB - Ethanol and benzo(a)pyrene cause lipid peroxidation either by producing the reactive oxygen species or decreasing the activities of antioxidant enzymes that lead to cellular damage and cellular dysfunction. In this study, we investigated both physiological and histological changes in lung and physiological changes in brain after the administration of benzo(a)pyrene and ethanol both separately and together. Male Sprague Dawley rats were divided into four groups, each containing seven rats as follows: Group I (control), group II (benzo(a)pyrene, [B(a)P]), group III ([B(a)P] + ethanol (EtOH)) and group IV (EtOH). Superoxide dismutase (SOD) activity, levels of glutathione(GSH), malondialdehyde (MDA) as well as histological examinations were evaluated to demonstrate the damages in lung and brain tissues following the administration of [B(a)P] and EtOH. SOD activities of lung and brain tissues in group II and group III decreased significantly, compared to that in group I and group IV, respectively. GSH levels of both the lung and brain tissues in the experimental groups were lower when compared to the control group. MDA levels of lung tissues in group II and III were significantly higher than that in the control group. Moreover, MDA levels in the brain tissues of all the experimental groups were higher than that in the control group, but these values were only significantly higher in group II and IV. In the second study group, [B(a)P] administration resulted in lung damage. On the other hand, lung tissue of the third experimental group showed moderate damage, and lung tissues of the fourth group was less severely damaged. [B(a)P] and EtOH administration alone or together caused changes in the GSH, MDA levels and SOD enzyme activity in the lung and brain tissues. We also noted that [B(a)P] and EtOH caused different degrees of histological changes. PMID- 17867436 TI - Pay-for-performance: the good, the bad, & the ugly. PMID- 17867437 TI - Is SIDS on the rise?? AB - OBJECTIVE: Sudden Infant Death Syndrome (SIDS) is defined as a diagnosis of exclusion, after an evaluation of the medical history, complete postmortem examination, and scene investigation. The diagnosis of SIDS in many sudden and unexplained infant deaths has not been consistently applied nationally or, prior to July 2003, in the state of Kentucky. In order to better standardize practices in formulating the diagnosis of SIDS in cases of sudden and unexpected infant deaths, all of the Kentucky medical examiners formed a working group to collectively standardize the classification of this enigmatic type of infant death. METHODS: We conducted a retrospective review (2000-2004) of infants < 1 year who underwent complete historical review, circumstantial investigation, postmortem examination, and toxicological analysis performed at the Medical Examiners' Offices in Kentucky encompassing all deaths certified as Sudden Infant Death Syndrome, positional asphyxia, overlay, and undetermined cause and manner of death. RESULTS: A total of 417 cases were deemed sudden unexplained infant deaths after postmortem examination at the Medical Examiners' Offices in Kentucky between 2000 and 2004. A total of 237 (56.8%) infants had been bedsharing with at least one other person when found. Prior to the SIDS classification policy change in July 2003, a significantly greater number of sudden unexpected infant death cases were deemed undetermined in both cause and manner in contrast to a smaller number classified as SIDS. After the policy change, the number of deaths classified as SIDS greatly surpassed the number classified as undetermined. CONCLUSIONS: The increase in the number of deaths consistent with SIDS and a reciprocal decline in cases reported as undetermined cause and manner of death in Kentucky is due to the uniformity and standardization of terminology, rather than an actual increase in the number of infant deaths. The Kentucky policy in July 2003 has been invaluable in ensuring uniform criteria in the diagnosis of SIDS and other categories of sudden unexpected death in infants < 1 year. PMID- 17867438 TI - ADHD and anxiety. PMID- 17867439 TI - Our aging population. PMID- 17867440 TI - Current concepts in the treatment of full-thickness rotator cuff tears. PMID- 17867441 TI - Reportable diseases. PMID- 17867442 TI - A doctor's story. PMID- 17867443 TI - Medicare beneficiaries have right to appeal hospital discharge. PMID- 17867444 TI - W. D. Miller: his origins and his influence 100 years on. PMID- 17867445 TI - A brief history of dental libraries in the United Kingdom and beyond. PMID- 17867446 TI - Nasmyth's membrane: confusion and controversy. PMID- 17867447 TI - Peripatetic dentistry: an out-of-surgery experience. PMID- 17867448 TI - The centenary of the formation of the British Society for the Study of Orthodontics. PMID- 17867449 TI - Medical ethics under a totalitarian regime: German dentists and the Third Reich. PMID- 17867450 TI - Dentistry in the 'wild west': the roots of the profession in western Canada. PMID- 17867451 TI - The development of dentistry in Trinidad and Tobago. PMID- 17867452 TI - A dental extraction': a patient's tale'. PMID- 17867453 TI - We apoligize. 'The Glasgow heritage' (Dental Historian, No 43). PMID- 17867454 TI - Comparative examination of percussional and echocardiographic determination of the cardiac dullness area in healthy horses. AB - Since percussion started to be a method forgotten and not trusted by many practitioners, the aim of the study was to demonstrate whether this procedure could deliver exact data if done accurately and by a practised examiner. The trial presented here included 31 healthy warm-blooded horses. Percussion of the area of cardiac dullness and then echocardiographic imaging of the same region were performed. To obtain the relevant measurement points, the 4th and 5th intercostal spaces (ICS) were used on the left and the 4th ICS on the right side. On the left side, the dorsal border of cardiac dullness was determined in the 4th ICS (1st point). Then the ventral border of the cardiac dullness was determined at the same place (2nd point). This was followed by the examination of the same points in the 5th ICS (3rd and 4th points). The following step was to measure the distance of these points from the ventral border of the thorax, and also that between the 2nd and the 4th points. On the right side the same procedure was used in the 4th ICS only. Mean values/standard errors (in cm) of absolute values of differences between percussional and echocardiographic measurements were as follow. Left side, 4th ICS, dorsal border: 0.8/0.1; ventral border: 0.7/0.1; 5th ICS, dorsal border: 0.8/0.1, ventral border: 0.9/0.2; right side, 4th ICS, dorsal border: 0.8/0.2; ventral border: 0.7/0.1. Due to the close correlation between the results of the two techniques, it is reasonable to consider cardiac percussion as an integrated part of the physical examination. PMID- 17867455 TI - Evaluation of the effect of ketoprofen and carprofen on platelet function in dogs studied by PFA-100 point-of-care analyser. AB - The effect of two nonsteroidal anti-inflammatory drugs (carprofen and ketoprofen) on platelet adhesion and aggregation functions was evaluated by the PFA-100 analyser (Dade-Behring, CA, U.S.A.) using its collagen-adenosine diphosphate (ADP) and collagen-epinephrine (EPI) cartridges. The function of platelets was evaluated in 55 healthy dogs, in 7 dogs treated with ketoprofen and in 31 dogs treated with carprofen in a therapeutic dose for minimum 5 days. The therapeutic doses of carprofen had no effect on the closure time of PFA-100 (which is the marker of platelet function) but ketoprofen caused a significant increase when using collagen-EPI stimulation The closure times for both the healthy (control) and the treated dogs using EPI cartridges were often longer than the upper default cut-off point (300 sec) of the device. The PFA-100 analyser with collagen ADP cartridges could be a useful tool for veterinary applications including the evaluation of platelet aggregation in dogs treated with NSAIDs. The upper cut-off point of PFA-100 might be extended. PMID- 17867456 TI - Effects of haemolysis, lipaemia and bilirubinaemia in canine C-reactive protein and haptoglobin determination by time-resolved fluorometry: short communication. AB - C-reactive protein (CRP) and haptoglobin (Hp) are well-known acute phase proteins in the dog. Currently, a commercial ELISA and a colorimetric assay are the methods of choice for measuring CRP and Hp, respectively; however, these assays showed interference when using haemolysed, lipaemic or hyperbilirubinaemic samples. Recently, time-resolved immunofluorometric assays (TR-IFMAs) have been developed for measuring canine CRP and Hp. The aim of the present study was to evaluate the effect of increasing concentrations of haemoglobin, lipids and bilirubin in CRP and Hp serum measurements using these new fluoroimmunoassays. Haemolysis was produced by freezing blood cells at -20 degrees C. The haemolysate was added to pooled sera at final concentrations of 0, 2.5, 5, 10, 20 and 40 g/L. A commercial emulsion of triglycerides was added to homologous pooled sera at 0, 0.35, 0.7, 1.4, 2.8, 5.6 and 11.2 mmol/L. Bilirubin, initially dissolved in dimethyl sulphoxide, was added to pooled sera at 0, 64.2, 128.4, 256.8, 513.7 and 1027.4 micromol/L. Addition of fresh haemolysate, triglycerides or bilirubin to serum samples did not affect either CRP or Hp concentrations (P > or = 0.18), so the TR-IFMAs could be an alternative to the traditional tests for measuring canine CRP and Hp in those laboratories where immunofluorometric assays are available. PMID- 17867457 TI - Closed reduction of coxofemoral luxation in a goat: case report. AB - Hip luxations have been reported in many ruminants, and several treatments have been described for them. However, successful closed reduction of hip joint luxation has not been reported in goats to date. This case report describes the closed reduction of coxofemoral luxation in a three-month-old male Saanen dairy goat. The goat showed non-weightbearing lameness and abnormal mobility of the proximal right hindlimb. Luxation of the right coxofemoral joint in craniodorsal direction was diagnosed by radiography. The femoral head was repositioned under sedation, and physiotherapy including non-weightbearing hindlimb movement and supported walking exercise was performed. Fifteen days after closed reduction the animal was discharged from the clinic. At that time the animal was sound at a slow walk but lameness was still present at faster gaits. Follow-up examinations revealed normal development of the animal, which subsequently showed no lameness and served successfully as a breeding goat. PMID- 17867458 TI - Application of arm-specific painting probes of horse X chromosome for karyotype analysis in an infertile Hutsul mare with 64,XX/65,XX+Xp karyotype: case report. AB - A 5-year-old infertile Hutsul mare was subjected to cytogenetic analysis. Fluorescence in situ hybridisation (FISH) using the equine Xp and Xq chromosome painting probes was carried out on chromosome preparations obtained after blood lymphocyte culture. These probes were generated by chromosome microdissection and a large number of spreads was analysed (525). The karyotype formula of the analysed mare was 64,XX/65,XX+Xp with the ratio of the two lines being 99.4 and 0.6, respectively. The goal of the study was to apply chromosome microdissection and the FISH technique for cytogenetic diagnostics. PMID- 17867459 TI - Experimental study on the role of Brachyspira alvinipulli in intestinal spirochaetosis of geese. AB - Ten one-day-old goslings were inoculated orally with a Brachyspira alvinipulli strain isolated from the large intestine of geese that had died of intestinal spirochaetosis (Group A), 10 day-old goslings were inoculated orally with a B. hyodysenteriae strain (Group B), and a third group of 10 goslings (Group C) served as uninfected control. The goslings were observed daily for clinical signs. They were sacrificed on days 7, 14, 21 and 35 days postinfection (PI), and necropsied. Segments of the large intestine were subjected to histopathological, immunohistochemical, electron microscopic (TEM, SEM) and microbiological examinations. Mortality did not occur during the experimental period. However, in both groups the caecum of the goslings killed by bleeding was slightly dilated, in its lumen there was a watery, yellowish and frothy content, and the mucous membrane was slightly swollen. By histopathological, immunohistochemical and electron microscopic examination, B. alvinipulli and B. hyodysenteriae could be detected in the caecum or colon, in the lumen of the glands and sometimes among the glandular epithelial cells in goslings of the respective groups, and could be reisolated from these organs by culturing. A mild inflammation of the intestinal mucosa was also noted. In transverse section of the brachyspirae, numerous (16 22) periplasmic flagella could be detected inside the outer sheath, also depending on the plane of section. PMID- 17867460 TI - First occurrence of periosteal chondroma (juxtacortical chondroma) in Uromastyxmaliensis (Reptilia: Sauria: Agamidae). AB - The occurrence of a periosteal chondroma (juxtacortical chondroma) in an adult male Uromastyx maliensis is documented for the first time. The chondroma developed near the right shoulder joint from the periosteal membrane, causing partial atrophy in the surrounding skeletal muscles. In the chondroma tissues widespread central necrosis and secondary calcium salt deposition were observed. Monomorphic chondrocytes were irregularly spread in the chondromucin matrix. The lizard had locomotor problems due to irritation of the periosteum and reduced movement of the bones constituting the shoulder joint caused by the chondroma. PMID- 17867461 TI - Oestrogens in the mammalian brain: from conception to adulthood--a review. AB - Environmental and plant oestrogens have been identified as compounds that when ingested, disrupt the physiological pathways of endogenous oestrogen actions and thus, act as agonists or antagonists of oestrogen. Although the risks of exposure to exogenous oestrogens (ExEs) are subject to scientific debate, the question of how ExE exposure affects the central nervous system remains to be answered. We attempt to summarise the mechanisms of oestrogenic effects in the central nervous tissue with the purpose to highlight the avenues potentially used by ExEs. The genomic and rapid, non-genomic cellular pathways activated by oestrogen are listed and discussed together with the best known interneuronal mechanisms of oestrogenic effects. Because the effects of oestrogen on the brain seem to be age dependent, we also found it necessary to put the age-dependent oestrogenic effects in parallel to their intra- and intercellular mechanisms of action. Finally, considering the practical risks of human ExE exposure, we briefly discuss the human significance of this matter. We believe this short review of the topic became necessary because recent data suggest new fields and pathways for endogenous oestrogen actions and have generated the concern that the hidden exposure of humans and domestic animal species to ExEs may also exert its beneficial and/or adverse effects through these avenues. PMID- 17867462 TI - Evaluation of goose serum amyloid a acute phase response by enzyme-linked immunosorbent assay. AB - Serum amyloid A (SAA) is of interest as the circulating precursor of amyloid A protein, the fibrillar component of AA (secondary) amyloid deposits, and also as an extremely sensitive and rapid major acute phase protein. Serum concentrations of acute phase proteins (APPs) provide valuable information about the diagnosis and prognosis of various diseases, and thus the relevance of APPs for monitoring the health status of domestic animals is widely accepted. More importantly, the measurement of SAA concentration assists in assessing the prognosis in secondary amyloidosis, which is a common disease of geese, affecting an increasing number of animals. In the present study we introduce a highly sensitive goose-specific ELISA method for measuring SAA concentration in goose serum or plasma samples. Samples were taken from geese of the Landes Grey and Hungarian White breeds, which were stimulated for an acute phase reaction by administration of a commercially available fowl cholera vaccine containing inactivated Pasteurella multocida. Strong and characteristically rapid acute phase responses were measured in both breeds, peaking at approximately 24 h after inoculation. The maximum SAA concentration was 1200 microg/ml. At 72 h postinoculation, the concentrations returned to pre-inoculation values. There was significantly (p = 0.004) less intense response in the control groups; however, a very mild increase of SAA levels was detected due to the stress inevitably caused by the sampling procedure. PMID- 17867463 TI - Phytoestrogens alter cortisol and androstenedione secretion by porcine adrenocortical cells. AB - The effect of plant-derived, nonsteroidal estrogens (genistein, daidzein and biochanin A) on cortisol and androstenedione secretion by porcine adrenocortical cells was examined. Adrenals were harvested from locally slaughtered mature gilts on days 5-9 of the oestrous cycle. Adrenocortical cells were incubated with or without genistein, daidzein, biochanin A (0.5, 5, 10 or 50 microM), oestradiol (10, 50, 100 or 500 pg/mL) and ACTH (5 nM--positive control). All incubations were performed for 8 h (95% air and 5% CO2, 37 degrees C). ACTH increased cortisol and androstenedione secretion. Genistein, daidzein and biochanin A suppressed cortisol output, whereas androstenedione secretion was enhanced by these phytoestrogens. In contrast, oestradiol did not alter steroid secretion by porcine adrenocortical cells, which may suggest that phytoestrogens have a non oestrogenic mechanism of action. Therefore, phytoestrogens present in commercial forage may influence adrenocortical function in pigs by decreasing cortisol and increasing androstenedione secretion. PMID- 17867464 TI - Piezo-actuated zona-drilling improves the fertilisation of OPS vitrified mouse oocytes. AB - The present study was designed to investigate fertilisation of open pulled straw (OPS) vitrified mouse oocytes drilled with piezo-micromanipulation method and their subsequent in vitro and in vivo developmental capacity. Ovulated mouse oocytes were vitrified using the OPS method. After warming, the zona pellucida of a group of vitrified-warmed oocytes was drilled by piezo-micromanipulation. Groups of (a) vitrified, (b) vitrified/drilled and (c) fresh control oocytes were fertilised in vitro. The fertilisation rate of vitrified-warmed oocytes was significantly lower than that of fresh oocytes (45.0 +/- 12.6% vs. 85.2 +/- 6.8%, P < 0.05), and was significantly improved by zona-drilling (85.4 +/- 7.3%). However, blastocyst formation rates of the vitrified and vitrified/drilled groups were significantly lower than those of the fresh controls (65.7 +/- 7.0% and 66.4 +/- 2.5% vs. 86.6 +/- 4.3%, respectively, P < 0.05). The cell number of blastocysts from the vitrified/drilled or the vitrified group was not different from that of the controls. Embryo transfer resulted in pregnancy in all three groups, but the rate of development to term was lower in the vitrified/drilled or vitrified groups than in the controls (16.6 +/- 0.7% or 36.0 +/- 2.4% vs. 51.3 +/ 2.9%, respectively). Our results demonstrated that zona-drilling with piezo micromanipulation could improve fertilisation in OPS vitrified mouse oocytes but did not increase the overall number of vitrified oocytes developing to term. PMID- 17867465 TI - Short-term effects of prepubertal ovariohysterectomy on skeletal, physical and behavioural development of dogs up to 24 weeks of age. AB - This study investigated the effects of ovariohysterectomy performed at 10 weeks of age on body weight, behaviour, bone length, serum calcium and phosphorus concentrations and gonadal hormone (progesterone and oestradiol) levels until 24 weeks of age in 31 clinically healthy mixed-breed female puppies. The littermates were randomly assigned to three groups. Group I (n=11) was completely ovariohysterectomised, Group II (n=10) was incompletely ovariohysterectomised with one ovary left intact, and Group III (n=10) was sham operated. No significant differences were found between the groups for any of the parameters evaluated. It was determined that, except for two measurements of two animals in Group II at 20 and 24 weeks of age, all animals had undetectable concentrations of oestradiol 17-beta. These findings suggest that an ovariohysterectomy performed on a mixed-breed dog at 10 weeks of age does not affect her skeletal, behavioural or physical development in the period studied, i.e. until 24 weeks of age. PMID- 17867466 TI - First description of postweaning multisystemic wasting syndrome (PMWS) in wild boar (Sus scrofa) in Croatia and phylogenetic analysis of partial PCV2 sequences. AB - This report describes the first case of postweaning multisystemic wasting syndrome (PMWS) in wild boar in Croatia. During the winter season of 2004, eight wild young piglets (of approximately 2 to 5 months of age) were found dead in a fenced hunting area. Polymerase chain reaction (PCR) was carried out on mesenteric lymph nodes and all animals yielded positive results. In one of these animals diagnosis of PMWS was established based on the three key diagnostic criteria including the clinical manifestation, moderate lymphoid lesions consisting of lymphocyte depletion and granulomatous inflammation, and detection of the presence of PCV2 genome within the lymphoid lesions by in situ hybridisation (ISH). Three additional wild piglets had also mild PMWS-like lesions and a low amount of PCV2 was also found. No PMWS-like lesions or PCV2 genome were detected in the rest of the wild piglets studied. Three PCR-positive isolates were partially sequenced, which confirmed the diagnosis of PCV2 and demonstrated that the three sequences were genetically identical. The phylogenetic analysis of a representative PCV2 isolate indicated that its sequence (DQ875444) is grouped in a separate branch with Hungarian isolate (AY256460) and differs from any of the annotated sequences. PMID- 17867467 TI - Diagnostic potential of recombinant protein of hexahistidine tag and infectious bursal disease virus VPX expressed in Escherichia coli. AB - The current method to detect antibody titre against infectious bursal disease virus (IBDV) in chickens is based on enzyme-linked immunosorbent assay (ELISA) using whole virus as coating antigen. Coating the ELISA plates requires a purified or at least semi-purified preparation of virus as antigen, which needs special skills and techniques. In this study, instead of using whole virus, recombinant protein of hexahistidine tag (His 6 tag) and VPX protein of IBDV expressed in E. coli was used as an alternative antigen to coat the ELISA plates. There was a good correlation coefficient (R2 = 0.972) between the results of the ELISA using plates coated with monoclonal antibody against His 6 tag and those of the commercial IBDV ELISA kit. Hence, His 6 tag and VPX recombinant protein expressed in E. coli has the potential for the development of ELISA for the measurement of IBDV-specific antibody. PMID- 17867468 TI - Evolution of clinical pharmacology: a step towards safe and rational prescribing of drugs. PMID- 17867469 TI - Comparative predictive value of three prognostic markers--S-phase fraction, PCNA and Mitotic count on axillary lymph node metastasis in carcinoma breast. AB - BACKGROUND: Axillary lymph node metastasis is the single most important prognostic factor in carcinoma of the breast. Therefore, prognostic markers that may reliably predict probability of lymph node (LN) metastases are of great value. This study was conducted to compare the predictive value of two novel prognostic / proliferative markers i.e. S-phase fraction (SPF) and proliferating cell nuclear antigen (PCNA) in parallel with mitotic index. METHODS: Data of consecutive cases of infiltrating ductal carcinoma (IDC) breast diagnosed from July 2003 to July 2004 at the section of the Histopathology, The Aga Khan University Hospital, Karachi, were reviewed. Atotal of 112 cases of infiltrating ductal carcinoma (IDC) of the breast with axillary LN sampling were selected. SPF was calculated by flow cytometry while PCNA staining was done by immunohistochemistry. Mitotic count was calculated according to modified Bloom and Richardson's grading guidelines. RESULT: It was observed that the number of axillary LN metastases was increased with higher SPF (p value: 0.008). However no significant difference was found between the results of various categories of PCNA on axillary LN metastases (p value: 0.182) and mitotic count with axillary lymph node metastases (p value: 0.324). CONCLUSION: It was concluded that mitotic count and / PCNA alone cannot be used in predicting axillary LN metastases. SPF was found to be a more reliable marker compared to PCNAreactivity and conventional mitotic count in predicting axillary LN metastases. PMID- 17867470 TI - Flexor tendon injuries of hand: experience at Pakistan Institute of Medical Sciences, Islamabad, Pakistan. AB - BACKGROUND: Flexor tendon injury is one of the most common hand injuries. This initial treatment is of the utmost importance because it often determines the final outcome; inadequate primary treatment is likely to give poor long tem results. Various suture techniques have been devised for tendon repair but the modified Kessler's technique is the most commonly used. This study was conducted in order to know the cause, mechanism and the effects of early controlled mobilization after flexor tendon repair and to assess the range of active motion after flexor tendon repair in hand. METHODS: This study was conducted at the department of Plastic Surgery, Pakistan Institute of Medical Sciences, Islamabad from 1st March 2002 to 31st August 2003. Only adult patients of either sex with an acute injury were included in whom primary or delayed primary tendon repair was undertaken. In all the patients, modified Kessler's technique was used for the repair using non-absorbable monofilament (Prolene 4-0). The wound was closed with interrupted non-absorbable, polyfilament (Silk 4-0) suture. A dorsal splint extending beyond the finger tip to proximal forearm was used with wrist in 20-30 degrees palmer flexion, metacarpophalangeal (MP) joint flexed at 60 degrees. Passive movements of fingers were started from the first post operative day, and for controlled, active movements, a dynamic splint was applied. RESULTS: During this study, 33 patients with 39 digits were studies. 94% of the patients had right dominated hand involvement. 51% had the complete flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) injuries. Middle and ring fingers were most commonly involved. Thumb was involved in 9% of the patients. Zone III(46%) was the commonest to be involved followed by zone II (28%). Laceration with sharp object was the most frequent cause of injury. Finger tip to distal palmer crease distance (TPD) was < 2.0 cm in 71% cases (average 2.4cm) at the end of 2nd postoperative week. Total number of patients was 34 at the end of 6th week. TPD was < 2.0 cm in 55% patients and < 1.0 cm in 38% cases (average 1.5cm) at the end of 6th week. Total 9 patients were lost to the follow up at the end of 8th week. TPD was < 1.0 cm in 67% (average 0.9 cm) at the end of 8th postoperative week. No case of disruption of repair was noted during the study. CONCLUSION: Early active mobilization programme is essential after tendon repair. Majority of the patients (92%) had fair to good results at the end of 2nd week which increased to 97% at the end of 8th week to good to excellent. PMID- 17867471 TI - Liver dysfunction in Dengue infection: an analysis of the previously published Thai cases. AB - BACKGROUND: Dengue infection is a major vector-borne disease. The classical sings and symptoms of this infection include high fever, violent headache, chill and rash. However, there are a number of atypical forms of dengue infection including those presented with liver dysfunction. However, there are only a few reports concerning the liver dysfunction among the patients with dengue infections. METHODS: Here, the author presents a summative study on the liver dysfunction and its clinical correlation among Thai patients in the previous studies. A literature review on the prospective studies concerning liver function and dengue infection in Thailand was performed. RESULTS: According to this study, there are 4 reports included covering 191 Thai pediatric patients with dengue infection. The overall rate of liver dysfunction among 191 subjects is 34.6 % (66/191). The rate of liver dysfunction among the patients without shock (36/120) is not significant different from those with shock. The rate of liver dysfunction in this study is considerable high, similar to the previous reports from other developing Asian countries. In addition, about 8 % (5/66) the patients with liver dysfunction developed hepatic encephalopathy. CONCLUSIONS: This can imply the importance of detection of abnormal high transaminase enzyme among the patients with dengue infection since the consequently developed hepatic encephalopathy can be expected. PMID- 17867473 TI - Screening for diabetic retinopathy: a comparative study between hospital and community based screening and between paying and non-paying patients. AB - BACKGROUND: Prevalence of diabetes and diabetic retinopathy varies in the population considering the background and financial status. METHODS: A total of 79,194 people more than 40 years, were screened for diabetes both in the community and eye hospital setting. Initial screening was carried out by urine dipstick followed by random blood sugar examination. A value > or =140 mg/dl of blood sugar was considered positive for diabetes. All the diabetics were then examined for any evidence of diabetic retinopathy through indirect ophthalmoscopy in a dilated pupil by a midlevel ophthalmologist. Health education campaign at public, patient and professional level was also conducted. RESULTS: The results of screening were analyzed for three distinct groups; rural population, hospital based free patients and hospital based paying patients. The prevalence of diabetes was found to be 9.12%, 10.34% and 18.57% in rural community, poor hospital and affluent hospital groups respectively. The prevalence of diabetic retinopathy in the total screened population in these three subgroups was 1.92%, 2.52% and 4.42% respectively, while this prevalence in the diabetic population was 21.05%, 24.39% and 23.80% respectively. The cost per person screened was $2.6 3.4, while the cost per diabetic identified was $26-28 and the cost per patient of diabetic retinopathy identified was $ 108-135. CONCLUSION; The prevalence of diabetic retinopathy was two times more in the affluent hospital patients as compared to poor hospital patients or rural population. For each known diabetic, there were four previously undiscovered diabetics in the rural population, and two previously undiscovered diabetics in hospital based population. PMID- 17867472 TI - Analysis of tracheobronchial foreign bodies with respect to sex, age, type and presentation. AB - BACKGROUND: Foreign body inhalation is one of the life threatening emergencies. It may happen at any age, however, most of these accidents occur in children especially below the age of five. METHODS: This prospective study was done at Department of Otolaryngology, Head and Neck Surgery, Ayub Teaching Hospital, Abbottabad, from 1 January 2003 to 30 June 2005. A total of Eighty one patients, referred from the casualty and Paediatric unit with suspicion of tracheobronchial foreign body were included in the study. RESULTS: Eighty one were studied. Fifty (61.7%) were male and thirty one (38.3%) were female. Sixty three (77.8%) were below five years, thirteen (16%) were between five and fifteen years and five (6.2%) were above fifteen years. Sixty seven patients (82.7%), presented mainly with chocking, while fifty nine patients (72.8%) had stridor and forty five patients (55.6%) had cough at initial presentation. Seventy two (88.9%) patients had decreased air entry and forty two (51.9%) had wheeze on auscultation, whereas cyanosis was noticed in five (6.2%) patients. Peanut was the commonest foreign body, retrieved in forty five patients (55.6%). Other foreign bodies were whistle (18.5%), maize seed (13.6%), bean seed (6.2 %), nuts (2.5%), sewing needle with thread, dice and denture (1.2%) each. CONCLUSIONS: Foreign body inhalation is more common in male patients, mostly below five years of age. Chocking is the commonest symptom and decreased air entry on auscultation is the typical examination finding. Peanut has been found to be the commonest type of foreign body. PMID- 17867474 TI - Anterior cervical reconstruction using titanium mesh cages. AB - BACKGROUND: Surgical management of cervical lesions with reconstruction procedures has remarkably expanded the options available in the last decade. Anterior cervical corpectomy with titanium mesh reconstruction is one of the effective method of cervical spine reconstruction. METHODS: We studied 17 consecutive cases in whom corpectomy and decompression was performed. Fusion with titanium mesh cages filled with local bone pieces were placed inside the cage. RESULTS: Clinical status improved in 13 patients whereas in 3 it remained unchanged, based on Nurick's classification. At 3 months follow up, 13 (76.4%) patients reported successful arm pain relief and 12 (70.5%) with neck pain relief with visual analog score below five. Complications included cage in kyphosis, radiculopathy, cage subsidence and wound infection. CONCLUSION: Outcome after cervical fusion procedures with a titanium mesh cage lead to early and good stability of the cervical spine, excellent neurological improvement, low risk of complication and rare need for endogenous bone graft harvest avoiding donor site morbidity, less postoperative pain and decreased hospital stay and cost. PMID- 17867475 TI - Guillain Barre syndrome: the leading cause of acute flaccid paralysis in Hazara division. AB - BACKGROUND: Acute flaccid paralysis (AFP) can be caused by a number of conditions. A common preventable cause is poliomyelitis which is still being reported in Pakistan, Guillain Barre Syndrome (GBS), also known as Acute Inflammatory Demyelinating Polyneuropathy, is another common cause of acute flaccid paralysis. It is important to recognize GBS in childhood as parents consider all acute flaccid paralysis to be due to poliomyelitis. The present study was designed to know the frequency of different causes of acute flaccid paralysis in Hazara division. METHODS: This is a retrospective analysis of cases of acute flaccid paralysis reported from various districts of Hazara division during the period January 2003 to December 2004. Acute flaccid paralysis was diagnosed clinically through history and clinical examination. The underlying cause of acute flaccid paralysis was investigated by appropriate laboratory tests, such as serum electrolytes, cerebrospinal fluid analysis, electromyogram, nerve conduction study and stool culture for polio virus and other enteroviruses. Diagnosis of Poliomyelitis was confirmed by stool testing for poliovirus. RESULTS: 74 patients presented with AFP during the study period. 36 were male and 38 were female. Guillain Barre syndrome and enteroviral encephalopathy were the two leading causes of acute flaccid paralysis. Majority of the cases were reported from Mansehra district. Children of age groups 12 to 24 months and > 96 months constituted the majority (20% each). CONCLUSION: Guillian Barre syndrome was the leading cause of acute flaccid paralysis reported from various parts of Hazara division. PMID- 17867476 TI - Chest radiographs in acute pulmonary embolism. AB - BACKGROUND: Pulmonary embolism (PE) is a serious clinical entity carrying significant morbidity and mortality. Clinically, it is a difficult condition to diagnose and remains under treated condition in Pakistan due to non-availability of objective tests and lack of awareness among physicians. This study was conducted to determine the chest radiographic presentation in known cases of acute PE presenting to a tertiary care hospital. METHODS: Hospital records of patients with a diagnosis of acute PE were reviewed from June 2000 until June 2004. Fifty diagnosed cases of acute PE on Spiral Computed tomography (CT) of the chest demonstrating an intraluminal-filling defect were selected. Two chest physicians reviewed the chest radiographs obtained during that hospitalization. In case of discrepancy, a radiologist made final interpretation. RESULTS: The chest radiograph was interpreted as normal in only 18% of patients with acute PE. The most common chest radiographic abnormalities were cardiac enlargement (38%), pulmonary parenchymal infiltrates (34%), atelectasis (26%), pleural effusion (24%), and pulmonary congestion (24%). Other rare findings were elevated hemi diaphragm (14%), pulmonary artery enlargement (14%), and focal oligemia (8%). CONCLUSIONS: Cardiomegaly is the most common chest radiographic abnormality associated with acute pulmonary embolism. Chest radiography is not useful in making the diagnosis of acute pulmonary embolism. Its major role is in identification of alternative disease processes that can mimic thrombo-embolism. PMID- 17867477 TI - Effect of a compound recipe (medicinal plants) on serum insulin levels of alloxan induced diabetic rabbits. AB - BACKGROUND: The present study was planned to observe the hypoglycaemic effect of the 'Compound recipe' a combination of traditional medicinal plants in normal and alloxan induced diabetes mellitus. This study was performed to study the possible role of indigenous medicinal plants in the regeneration of pancreatic beta-cells and in treatment of insulin dependent diabetes mellitus. METHODS: The 'Compound recipe' was administered daily in doses of 400-mg/kg body weight to normal and alloxan induced diabetic rabbits for a period of 4 months. The blood glucose and serum insulin levels were estimated before and 1, 2, 3 and 4 months after the administration of the extract. RESULTS: The extract exerted a significant (p<0.05) hypoglycemic effect in alloxan diabetic rabbits. The hypoglycemic effect was not significant (p>0.05) in normal rabbits. The extract exerted a significant (p<0.05) increase in insulin levels in alloxan diabetic rabbits. The effect on the insulin levels was not significant (p>0.05) in normal rabbits. The doses used did not show acute toxicity or result in behavioral changes. CONCLUSION: From this study it may be concluded that the Compound recipe causes an increase in serum insulin levels in alloxan induced diabetic rabbits possibly due to regeneration of pancreatic beta cells. PMID- 17867478 TI - Resistance patterns of urinary isolates in a tertiary Indian hospital. AB - BACKGROUND: To analyze the pathogenic organisms recovered from patients with urinary tract infection in a tertiary Indian hospital setting along with determination of the occurrence and antimicrobial sensitivity of uropathogens on a retrospective basis during a period of one year. METHODS: A total of 5073 urine samples were processed. Urine culture was done using conventional microbiological techniques. Biochemical testing was used to identify the organisms and antibiotic sensitivity was done by the Kirby Bauer method. RESULTS: A total of 2436 uropathogens were isolated. E coli were seen in 50.7% samples followed by Klebsiella sp (27.6%). Staphylococcus aureus was the commonest Gram-positive isolate (1.5%). Urinary tract infection (UTI) was seen in 70.5% females as compared to 29.5% males. A high recovery of isolates was noted from July to September. Multi drug resistance was commonest with Enterococcus (78.8%) followed by Pseudomonas (65.1%). Drugs, which retained usefulness for Gram-negative isolates, were amikacin, norfloxacin and cefotaxime. For Gram-positive isolates, vancomycin, teicoplanin, lincomycin and Norfloxacin were very effective. CONCLUSIONS: Our study highlights the changing etiology of UTI and emergence of drug resistance within the Indian subcontinent. PMID- 17867479 TI - Intraocular pressure after phacoemulsification using hydroxypropyl methylcellulose and sodium hyaluronate as viscoelastics. AB - BACKGROUND: Phacoemulsification and intraocular lens (IOL) implantation has resulted in early visual rehabilitation, increased wound stability and improved refractive results. Viscoelastic substances (VES) are important adjuncts in this type of surgery. Use of VES in phacoemulsification can be associated with adverse effects, the most common and potentially dangerous of which is the transient rise in intraocular pressure (IOP) in post-operative period. To evaluate the effects of viscoelastic substances on post-operative IOP after phacoemulsification with implantation of intraocular lens, a cross-sectional comparative, prospective study was conducted in the department of Ophthalmology, Combined Military Hospital, Peshawar, Pakistan, from October 2003 to March 2004. METHODS: One hundred patients were randomized into two groups of 50 each. Phacoemulsification with implantation of intraocular lens was performed in all the patients. 2% Hydroxypropyl Methylcellulose (HPMC) was used in one group and 1% Sodium Hyaluronate (NaHa) was used in the other group. IOP was measured pre-operatively as well as 24 hours and 7 days post-operatively. RESULTS: There was no significant difference in the pre-operative intraocular pressure between the two groups (p=0.483). Twenty four hours after surgery, the mean IOP increased by 2.84+/-SD 2.12 mm Hg in 2% Hydroxypropyl Methylcellulose group and 4.54+/-2.07 mm Hg in 1% Sodium Hyaluronate group. The increase was significantly higher in 1% Sodium Hyaluronate group as compared to 2% Hydroxypropyl Methylcellulose group (p=0.003). Seven days after surgery the mean intraocular pressure returned to near pre-operative levels in both the groups. CONCLUSION: Sodium Hyaluronate causes significantly higher increase in intraocular pressure in early post operative period after cataract surgery inspite of maximum aspiration of viscoelastic substance from the eye following phacoemulsification surgery. PMID- 17867480 TI - Frequency of hepatitis C infection in diabetic patients. AB - BACKGROUND: Diabetic patients are at an increased risk of acquiring Hepatitis C virus (HCV) infection owing to the nature of the disease and its inherent complications or frequent parentral exposure. On the other hand HCV infection may itself contribute to the development of Diabetes Mellitus. The epidemiological evidence of this association has not been studied in Pakistan at a population level and its exact biological mechanisms are not obvious. Objective of this study was to study the frequency of HCV infection among adult diabetic patients attending the Hospital. METHODS: The study comprised of 100 Diabetic patients visiting the out patient clinics or admitted in the medical wards of a Teaching Hospital, in Peshawar. Diabetes was confirmed according to the new diagnostic criteria based on 2 fasting or 2 random plasma glucose levels of more than 126 milligram per deciliter (mg/dL) and 200 mg/dL respectively. The presence of HCV infection was confirmed by Enzyme Linked Immuno-Sorbent Assay (ELISA) method. A concise history of the patient, examination and laboratory findings were recorded on a Performa. RESULTS: Out of the hundred diabetics, 36% were found to be anti HCV positive and all of them had type II diabetes. There was no gender difference in the seropositive cases. Serum Glutamic-Pyruvic Transaminase (SGPT) level was raised in 75% of the positive cases as compared to the 25% of the seronegative patients. The seropositive cases had a comparatively higher blood sugar level. CONCLUSION: HCV infection occurs more often in type II diabetics and further investigations should be done in diabetic patients with raised SGPT for the presence of chronic HCV infection. PMID- 17867481 TI - Outcome of modified open surgery in tennis elbow. AB - BACKGROUND: Tennis elbow is a common disorder of upper extremity. It can be treated conservatively in majority of the patients but some resistant cases eventually need surgery. MATERIAL & METHODS: This descriptive study was conducted at Department of Orthopaedics, Ayub Teaching Hospital, Abbottabad, from January 2002 to June 2006. Sixteen patients had surgical release of the extensor tendon origin along with excision of the lateral epicondyle ridge. These patients did not respond to conservative treatment i.e. rest, non- steroidal anti inflammatory drugs (NSAIDS), local steroid injections and physiotherapy. Patients were followed upto six months. Outcome was graded as excellent, good and poor according to pain relief and function of the hand. RESULTS: Sixteen patients (17 elbows) were studied. Thirteen were female (81.25%) and three were male (18.75%). Fifteen patients (93.75%) had unilateral Tennis Elbow, while one had bilateral involvement (6.25%). In unilateral disease, right side was affected in eleven patients (68.75%) and left side in four (25%). Excellent outcome was noticed in eleven patients (68.75%) and good result in five patient (31.25%). CONCLUSION: Open surgical technique of releasing extensor tendon origin along with excision of lateral condylar ridge of the humerus is new and simple procedure and yields excellent and good result in patients with resistant Tennis Elbow. PMID- 17867482 TI - Frequency of primary solid malignant neoplasms in both sexes, as seen in our practice. AB - BACKGROUND: To determine the frequency of various histologic types of primary solid malignant neoplasms in males and females, in our practice, in a large series of surgical biopsies. METHODS: A retrospective study of 20,000 consecutive surgical biopsies in the section of Histopathology, Aga Khan University Hospital (AKU), Karachi, in 2004. RESULTS: Squamous cell carcinoma of oral cavity was the commonest malignant neoplasm in males followed by diffuse Large B cell, Non Hodgkin's lymphoma and Prostatic adenocarcinoma. In females, infiltrating Ductal carcinoma of the breast was overwhelmingly the commonest malignant neoplasm followed by Squamous cell carcinoma of the oral cavity and esophagus. CONCLUSION: Out of 20,000 biopsies, there were 4616 (23.08%) malignant neoplsms. Carcinoma of oral cavity is very common in our population in both sexes. PMID- 17867483 TI - Transverse testicular ectopia. AB - We present a case of Transverse testicular ectopia of the right testis that presented to our surgical out patient department with left inguinal hernia and an impalpable testis in the right scrotum. Patient was operated. Left herniotomy was performed and right testis was found in the left inguinal canal which was brought to the right scrotum and anchored through suprapubic subcutaneous tunnel. PMID- 17867484 TI - Gastrograffin use in distal intestinal obstruction syndrome of cystic fibrosis. AB - BACKGROUND: Meconium ileus equivalent or the Distal Intestinal Obstruction Syndrome (DIOS) is an entity that is frequently seen in patients with cystic fibrosis (CF). In the gastrointestinal tract cystic fibrosis may produces symptoms of malabsorption and constipation. The latter may be associated with complications such as impaction and intestinal perforation. Meconium ileus and DIOS are an emergency and requires to be treated aggressively to ensure that consequences such as perforation do not occur. METHOD: Traditional modes of management of DIOS have included the use of laxatives, Acetylcysteine and Gastrograffin enemas. We are describing the use of oral gastrograffin in our patient seen at the Aga Khan University Hospital where small bowel obstruction was refractory to treatment. Oral gastrograffin was used once diluted in 4 times the volume of water or fruit juice with half doses given on day 2 and 3. RESULTS: Oral gastrograffin use was followed by relief of obstruction in this patient. CONCLUSION: Gastrograffin use orally or rectally may be helpful in the treatment of refractions distal intestinal obstruction syndrome in cystic fibrosis. PMID- 17867485 TI - Cystic hygroma--an unusual cause of induced abortion. AB - A male infant was diagnosed prenatally at 20 weeks of gestation with posterior cervical cystic hygroma. The mother was a 31-year-old gravida, who had an otherwise normal systemic examination. A therapeutic abortion was arranged and fetus was aborted. Sonographic findings were confirmed on examination of aborted fetus PMID- 17867486 TI - Malignant melanoma of the small bowel with unknown primary: a case report. AB - Primary small bowel tumours are rare. However, alongwith stomach it is the most frequent site for metastatic tumours, malignant melanoma being the commonest tumour. The prevalence of malignant melanoma in the gastrointestinal tract without any evidence of a primary lesion in the skin or any other site is extremely rare. PMID- 17867487 TI - Barbers' education; a window to improve the public about skin diseases. PMID- 17867488 TI - [The antibacterial activity of fluoroquinolones against gram-negative bacteria isolated from Gifu Prefecture (2005)]. AB - We investigated the susceptibility to 6 fluoroquinolones against 433 strains of Gram-negative bacteria isolated from 6 medical facilities in Gifu prefecture between January and September in 2005, determined by the agar dilution methods in according with the Japan Society of Chemotherapy. We also investigated the correlation between the degree of resistance to fluoroquinolones and the amino acid substitutions in the quinolone resistance-determining region (QRDR). The tested clinical isolates were as follows, Salmonella spp.; 17 strains, Escherichia coli; 112 strains Citrobacter freundii; 35 strains, Enterobacter cloacae; 31 strains, Klebsiella pneumoniae; 73 strains, Proteus spp.; 18 strains, Providencia spp.; 3 strains, Morganella morganii; 14 strains, Serratia marcescens; 27 strains and Pseudomonas aeruginosa; 103 strains. The number of the strains resistant to ciprofloxacin (CPFX) (MIC > or = 6.25 microg/mL) was twenty (E. coli; 14 strains, E. cloacae; I strain, Proteus spp.; 2 strains and P. aeruginosa; 3 strains). Among these strains, 12 strain (E. coli; 11 strains and E. cloacae; 1 strain) were highly resistant to CPFX (MIC > or =25 microg/mL). The E. coli strains highly resistant to CPFX had the multiple amino acid mutations in QRDR of ParC an GyrA. However in other strains, there was no strains possessing multiple mutations in both ParC and GyrA. PMID- 17867489 TI - In vitro activity of cefotiam against oxacillin-resistant Staphylococcus epidermidis strains--reevaluation of beta-lactam antibiotics efficiency on MRSE. AB - We evaluated the efficacy of cefotiam (CTM) against Staphylococcus epidermidis (S. epidermidis) isolated from blood culture and central venous catheters. Of the S. epidermidis strains tested, 82.3% were methicillin (MPIPC)-resistant (MPIPC MIC > or = 0.5 microg/ml) and expressed the mecA gene, and 89.2% of these MPIPC resistant S. epidermidis (MRSE) showed less than 8.0 microg/ml CTM MIC. In vitro killing kinetics of CTM against MRSE demonstrated that strains with high CTM MIC (> or = 4.0 microg/ml) showed high MPIPC MIC (> or = 4.0 microg/ml). All strains with low CTM MIC (< or = 2.0 microg/ml) showed MPIPC MIC lower than 2.0 microg/ml. In time-kill studies, CTM had high bactericidal activity against strains with low CTM MIC (< or = 2.0 microg/ml), regardless of whether they were mecA positive. These results demonstrated that MRSE isolates with low CTM MIC (< or = 2.0 microg/ml) are not easily induced CTM resistance by CTM treatment in vitro, and indicated the possibility that beta-lactams such as CTM could be an effective antibiotic agents against beta-lactam-sensitive MRSE infections. PMID- 17867490 TI - [Clinical efficacy of prolonged (4 hour) drip infusion of meropenem against severe pneumonia]. AB - To examine the clinical efficacy of antibacterial chemotherapy for life threatening pneumonia, we investigated the clinical outcome after a prolonged infusion regimen of meropenem based on a pharmacokinetics/pharmacodynamics (PK/PD) theory. In 42 patients with severe pneumonia, the clinical efficacy of a prolonged (4 h) drip infusion regimen of meropenem (4 h-group; 0.5 g, b.i.d.; 18 patients) was compared with that of a standard (0.5-1 hour) infusion regimen of meropenem (1 h-group; 0.5 g, b.i.d.; 24 patients). Although there was no significant difference in the duration of meropenem-administration and the rate of decrease in CRP between the 4 h-group and 1 h-group, the mortality rate in the 4 h-group (5.6%) was significantly lower (p < 0.05) than that in the 1 h-group (37.5%). In this study, the meropenem-concentration in the blood of each patient and the MIC of meropenem against the causative bacteria in each patient were not determined; however, it was thought that the superior life-saving effect of meropenem in the 4h-group was mainly due to prolongation of the time above MIC realized by the prolonged infusion regimen. These results suggested that prolongation of infusion time of meropenem was usefu for improvement of the clinical efficacy against life-threatening pneumonia. PMID- 17867491 TI - [Clostridium spp. isolated from surgical specimens]. AB - In the present study, the isolation rate of Clostridium spp. from surgical specimens and its antimicrobial susceptibilities were examined. Last 24 years, Clostridium spp. was isolated from 65 (1.8%) out of 3,644 specimens from the surgical abdominal infections. Clostridium spp. was most frequently isolated from secondary peritonitis such as perforated peritonitis, followed by hepato-biliary tract infection. There were 59 cases (90.8%) of mixed infection with Clostridium spp. and other bacteria. The rate of mixed infection with Bacteroides spp. (23.6%) was highest, followed by Escherichia coli (19.7%), other aerobic Gram negative rods and Enterococcus spp. Although Clostridium perfringens was highly sensitive to penicillins, cephems and carbapenems, a small number of Clostridium spp. other than Clostridium perfringens were resistant to cephems, erythromycin clindamycin and fosfomycin, respectively. PMID- 17867492 TI - [Discovery of novel bioactive small molecules from microbial metabolites and chemical biology research]. PMID- 17867493 TI - [Nontargeted effects of ionizing radiation: implications for low-dose exposures]. AB - The traditional thinking has been that the biological effects of ionizing radiation occur in irradiated cells as a consequence of the DNA damage they incur. This implies that: 1) biological effects occur only in irratiated cells, 2) radiation traversal through the nucleus of the cell is a prerequisite to produce a biological response, and 3) DNA is the target molecule in the cell. Evidence has been emerging, however, for non-DNA targeted effects of radiation; that is, effects including mutations, chromosomal aberrations, and changes in gene expression which occur in cells that in themselves receive no radiation exposure. Two of these phenomena will be described in this paper. The first is radiation-induced genomic instability whereby biological effects, including elevated frequencies of mutations and chromosomal aberrations, arise in the distant descendants of irradiated cells. The second phenomenon has been termed the "bystander effect", whereby in a mixed population of irradiated and nonirradiated cells, biological effects arise in those cells that receive no radiation exposure. The damage signals are transmitted from cell to cell through gap junction channels, and the genetic effects observed in bystander cells appear to result from an upregulation of oxidative stress. The possible influence of these non-targeted effects of radiation of the respounse to low-dose exposures is discussed. PMID- 17867494 TI - [Preirradiation heat shock protein induction increases cellular radioresistance]. AB - It was studied how does the transcriptional stress response and the heat shock protein (HSP) overexpression affect cellular radioresistance. For this purpose, normal murine fibroblasts and fibroblasts devoid of HSF1-gene (HSF1 is a transcriptional factor initiating stress-responsive HSP expression) were compared. Some cell samples were infected with specific vectors for expression of the constitutively active (mutant) HSF1 or individual HSP (HSP70, HSP56, HSP27). It was found that heat stress (43 degrees C, 30 min) increased the HSP level in normal fibroblasts and improved their survival following exposure to gamma radiation, with both the effects being suppressed by quercetin (an inhibitor of HSF1-mediated HSP induction). In the HSF1-deprived cells, heat stress caused neither the up-regulation of HSP levels nor the enhancement of radioresistance, although both the effects were well manifested following the active HSF1 expression in those cells. The vector-induced over-expression of HSP70 or/and HSP27 equally enhanced the radioresistance in both cell cultures infected. PMID- 17867495 TI - Shared oxidative pathways in response to gravity-dependent loading and gamma irradiation of bone marrow-derived skeletal cell progenitors. AB - Astronauts are exposed to radiation during space travel under conditions of dramatically reduced weightbearing activity. However, we know little about how gravity-dependent loading affects tissue sensitivity to radiation. We hypothesize gravity-dependent loading and irradiation share common molecular signaling pathways in bone cell progenitors that are sensitive to stress-induced reactive oxygen species (ROS), species capable of impacting skeletal health. To address this, progenitor cells with potential to differentiate into bone-forming osteoblasts were extracted from bone marrow, then cells were centrifuged (from 5 gravity (g) to 50-g for 5-180 min) on day 2 in culture, or were exposed to a single dose (1-5 Gy) of irradiation (137Cs 1 Gy/min) on day 3 or 4. Production of ROS was measured via fluorescence-activated cell sorting (FACS) using an oxidation-sensitive dye. Cell numbers were assessed by measurement of DNA content (CyQUANT). Osteoblastogenesis was estimated by measurement of alkaline phosphatase (ALP) activity and production of mineralized matrix (Alizarin Red staining). Transient centrifugation was a potent stimulus to bone marrow stromal cells, increasing production of ROS (1.2-fold), cell number (1.5-fold to 2.2 fold), and ALP activity (2.7-fold). Radiation also caused dose- and time dependent increases in ROS production (1.1-fold to 1.4-fold) by bone marrow stromal cells, but inhibited subsequent osteoblast differentiation. In summary, gravity-dependent loading by centrifugation stimulated ROS production and increased numbers of osteoblasts. Although radiation increased production of ROS by bone marrow stromal cells, cell number and differentiation of osteoprogenitors appeared reduced. We conclude gravity-dependent loading and radiation both stimulate production of ROS and affect critical bone cell functions including growth and differentiation. PMID- 17867496 TI - Mechanisms of action for an anti-radiation vaccine in reducing the biological impact of high dose and dose-rate, low-linear energy transfer radiation exposure. AB - The development of an anti-radiation vaccine could be very useful in reducing acute radiation syndromes. Existing principles for the treatment of acute radiation syndromes are based on the amelioration of progressive pathophysiological changes, using the concept of replacement therapy. Active immunization by small quantities of the essential radiation-induced systemic toxins of what we call the Specific Radiation Determinant (SRD) before irradiation increased duration of life among animals that were irradiated by lethal or sub-lethal doses of gamma-radiation. The SRD toxins possess antigenic properties that are specific to different forms of acute radiation sickness. Intramuscular injection of larger quantities of the SRD toxins induce signs and symptoms in irradiated naive animals similar to those observed in acute radiation syndromes, including death. Providing passive immunization, at variable periods of time following radiation, with preparations of immune-globulins directed at the SRD molecules, can confer some protection in the development of clinical sequelae in irradiated animals. Improved survival rates and times were observed in animals that received lower, sublethal doses of the same SRDs prior to irradiation. Therefore, active immunization can be induced by SRD molecules as a prophylaxis. The protective effects of the immunization begin to manifest 15-35 days after an injection of a biologically active SDR preparation. The SRD molecules are a group of radiation toxins with antigenic properties that correlate specifically with different forms of radiation disease. The SRD molecules are composed of glycoproteins and lipoproteins that accumulate in the lymphatic system of mammals in the first hours after irradiation, and preliminary analysis suggests that they may originate from cellular membrane components. The molecular weight of the SRD group ranges from 200-250 kDa. The SRD molecules were isolated from the lymphatic systems of laboratory animals that were irradiated with doses known to induce the development of cerebral (SRD-1), non-specific toxic effects (SRD-2), gastrointestinal (SRD-3) and hematological (bone marrow) (SRD-4) syndromes. Our results suggest that an anti-radiation vaccine can be developed for prophylactic use against radiation damage induced by acute exposure to significant doses of low Linear Energy Transfer (LET) radiation for humans, including nuclear power workers, commercial and military pilots, cosmonauts/astronauts, nuclear-powered engine vessel operators and possibly even the civilian population in the case of a nuclear terrorism event. PMID- 17867497 TI - Biophysical modelling of DNA DSB repair following high LET irradiation. AB - One of the quantitative methods used in DNA repair research is a measurement of the size-distribution of DNA fragments at different times following cell irradiation. The aim of the present study was to evaluate the relationship between the experimentally observed size-distributions of DNA fragments and the parameters of doublestrand break (DSB) repair. A biophysical model of DNA DSB repair in chromosomal DNA including DSB clusters repair was proposed. Complex shapes of (1) DNA fragments distribution at different repair times, (2) rejoining kinetics for DNA fragments in different length intervals, (3) total fragments rejoining kinetics were simultaneously described with rates of DSB repair different for active/inactive chromatin compartments. PMID- 17867498 TI - Development of genetic instability in mice in response to chronic irradiation simulating high-altitude flight conditions. AB - The purpose of this work was to study the chronic influence of the high-energy radiation field formed in the atmosphere at an altitude of 10 to 30 km on the level of DNA damage in leukocytes of peripheral blood in mice. The external radiation field (behind the concrete shield) of the U-70 accelerator (Serpukhov, Russia) was used for these studies. This radiation field simulates the components and spectral composition of the high-energy radiation field formed in the atmosphere at an altitude of 10 to 30 km. Two groups of SHK line mice were chronically irradiated with a total dose equivalent to 21.5 and 31.5 cGy. The state of the genome of nucleated blood cells was assessed by the Comet assay (alkaline version) 72 h after completion of chronic irradiation. The level of genome damage in individual peripheral blood leukocytes of irradiated animals was compared with the basal level of DNA lesions in peripheral blood leukocytes of unirradiated control mice. The damage was expressed in %TDNA (the amount of DNA found in the "comet tail" in percent of total DNA in the "comet"). It was found that in mice exposed to the radiation field of the accelerator, the mean value of DNA damage was: %TDNA = 3.88 +/- 0.35% for a dose of 21.5 cGy and % TDNA = 6.00 +/- 0.82% for a dose of 31.5 cGy. In mice irradiated at an X-ray therapeutic device with a dose of 150 cGy 24 h before the examination, %TDNA was 2.27 +/- 0.34% and this did not differ from %TDNA in unirradiated mice, 2.68 +/- 0.56%. We suggest that the increased level of DNA damage observed in mice irradiated with 31.5 cGy from the mixed radiation field at the Serpukhov accelerator points to the development of genetic instability in their leukocytes as a result of chronic exposure of animals to this particular radiation field. PMID- 17867499 TI - Effects of heavy ions and energetic protons on normal human fibroblasts. AB - At the low particle fluences of radiation to which astronauts are exposed in space, "non-targeted" effects such as the bystander response may have increased significance. The radiation-induced bystander effect is the occurrence of biological responses in unirradiated cells near to or sharing medium with cells traversed by radiation. The objectives of this study were to establish the responses of AG01522 diploid human fibroblasts after exposure to several heavy ions and energetic protons, as compared to X-rays, and to obtain initial information on the bystander effect in terms of cell clonogenic survival after Fe ion irradiation. Using a clonogenic survival assay, relative biological effectiveness (RBE) values at 10% survival were 2.5, 2.3, 1.0 and 1.2 for 1 GeV/amu Fe, 1 GeV/amu Ti, 290 MeV/amu C and 1 GeV/amu protons, respectively, compared to 250 kVp X-rays. For induction of micronuclei (MN), compared to the low LET protons, Fe and Ti are very effective inducers of damage, although C ions are similar to protons. Using a transwell insert system in which irradiated and unirradiated bystander cells share medium but are not touching each other, it was found that clonogenic survival in unirradiated bystander cells was decreased when irradiated cells were exposed to Fe ions or X-rays. The magnitude of the decrease in bystander survival was similar with both radiation types, reaching a plateau of about 80% survival at doses of about 0.5 Gy or larger. PMID- 17867500 TI - [The state of hemopoiesis under conditions of long-term bone marrow irradiation in residents of the Techa riverside villages]. AB - The paper presents the results of a 50-year study on the state of hemopoiesis in the Techa riverside residents chronically exposed to radiation in the range from low to intermediate doses. The highest bone marrow doses were attributable to intakes of osteotropic 9OSr with drinking water and local food products. During the period of maximum radiation exposures (1951-1953) exposed residents were manifesting decreased counts of peripheral blood leukocytes (neutrophils and lymphocytes) and thrombocytes. Normal counts of erythrocytes were maintained owing to the effect of sufficient compensatory mechanisms, including accelerated rates of erythrocaryocyte proliferation and maturation. The development of peripheral blood granulocytopenia was influenced by the delay in the differentiation of neutrophilic bone-marrow granulocytes at the myelocyte phase, a marked increase in the frequency of lethal abnormalities in bone-marrow neutrophils, and pathological mitoses. The period of normalization of the blood cell composition was significantly variable for different blood cell series, and was noted to depend on exposure dose rate, extent of the primary hemopoiesis inhibition and specific physiological characteristics of exposed individuals. PMID- 17867501 TI - [The radioactive contamination dynamics of water body ecosystems of different types in the Chernobyl atomic station alienation zone in Belarus]. AB - The long-term (1986-2005) gamma-activity dynamics in dominating zoobenthos species and the bottom sediments in the inlet of Pripyat river and the non flowing Perstok lake within the Chernobyl alienation zone was determined. Immediately after the accident (1986-1987) zoonehthos y-activity achieved the maximal values (up to 300-1100 kBq/kg) and after that began to decline steadily due to natural decay of man-caused radionuclides of "Chernobyl origin". Up to summer 2005 gastropod mollusks gamma-activity (Lymnaea stagnalis, Viviparus viviparus) approached to the natural level (less than 6 Bq/kg) in the inlet of Pripyat river, but it remained at the very high level up to 979-1638 Bq/kg in the Perstok lake. The positive correlation between gamma-activity of mollusks and bottom sediments has been established. In turn, the long-term variations of atmospheric precipitate amounts which wash down radionuclides from surrounding territories to water bodies and the amounts of annual flow of the Pripyat river as well as shoreline position changes in water bodies within the Chernobyl alienation zone influence on these values too. PMID- 17867502 TI - [Animal death after exposure to ultra-high frequency waves in the dependence of power flux density and specific absorption rate]. AB - A comparative analysis and mathematical modeling of laboratory animal sensitivity (mice, rats, rabbits and dogs) to microwave exposure in the dependence of the power flux density (PFD) and the specific absorption rate (SAR) were carried out. The results obtained in our laboratory and some data published by other authors were presented as the dependence of the survival time of various animals during exposure both on PFD and SAR of microwave radiation (0.46; 2.4 and 7 GHz). It is shown that if PFD is used as a dosimetric parameter, the animal sensitivity to nonionizing electromagnetic ultrahigh frequency radiation increased with animal mass. If SAR was used as a dosimetric parameter, the arrangement of animals in accordance with their sensitivity to microwave became quite opposite. Mathematical equations describing the dependence of the survival time of laboratory animals on the duration and the intensity of microwave radiation were obtained. These equations describe the published experimental data and can be used to predict the animal death during the process of microwave irradiation. PMID- 17867503 TI - [The assessment of modulated radiofrequence electromagnetic radiation on cognitive function in rats of different ages]. AB - The modulated radiofrequence electromagnetic radiation influence on cognitive function of male uninbred Wister rat exposed at the age of sexual maturation (2 months) and at the age of morphofunctional maturity (3.5 months) was examined. Animals were subjected to pulse electromagnetic radiation (925 MHz) modulated as a GSM standard with the power density 1.2 mW/cm2 for 10 minutes every day for 12 days. At day 8 of exposure the cognitive function were examined with the Morris water maze. In the result of investigation it was determines that modulated radiofrequence electromagnetic radiation at the sexual maturation age did not affect the spatial learning and improve the visual orientation performance. Modulated radiofrequence electromagnetic exposure of animals at the sex maturity age did not affect the visual performance and improve the spatial performance of male rats. PMID- 17867504 TI - [The influence of variable and constant magnetic fields on biota and biological activity of ordinary chernozem soils]. AB - In model experiments on influence variable magnetic fields of industrial frequency (50 Hz) an induction of 1500 and of 6000 mkTl and the constant magnetic field an induction of 6000 mkTl and of 15000 mkTl during 5 days of exposure on biological properties of chernozem ordinary is shown, that the soil microflora is more sensitive to magnetic fields, than enzymes activity. Bacteria are more sensitive, than microscopic mushrooms. Dehydrogenase it is steady against influence of all variants. Constant magnetic field by the induction of 15000 mkTl rendered practically identical authentic overwhelming influence on catalase and saccharase activity - on 51 and 47% accordingly. PMID- 17867505 TI - [The clonal structure of dandelion coenopopulations under conditions of radioactive contamination in the Urals]. AB - The diversification of rare and unique morphs of some ferment systems and the clonal structure of dandelion coenopopulations, growing in radioactive contaminated drained watershed and flood-land ecosystems in the Ural region was studied. Drained watershed and flood-land dandelion coenopopulations significantly differed in the number of rare and of unique morphs and in the clonal structure. In the gradient of contamination in the drained watershed coenopopulations (zone of East-Urals radioactive trace) the share of rare morphs in most ferments systems increased, while the number of clones decreased. In two flood-land coenopopulations of the Techa River essential differences in the enzyme structure were observed, but these peculiarities were not connected with the level of radioactive contamination. PMID- 17867506 TI - [Radiological estimation of the protective measures used in agricultural complex of Belarus Republic in 2000-2005 (20 years after the accident on the Chernobyl NPP)]. AB - The radiological estimation of the basic agrochemistry measures spent for the agriculture of the Republic of Belarus in 2000-2005 is given. Laws of behavior radionuclides 137Cs and 90Sr in agrosystems are considered depending on used protective a measures (countermeasures) and the primary goals on liquidation of consequences in sphere of agrarian and industrial complex which are necessary for solving during the remote period after accident ChNNP (in 2006-2010) are studied. PMID- 17867507 TI - [On the problem of radioadaptation in small mammals (ecological specialization of species, radioresistance, hemopoiesis, immunity)]. AB - The data illustrating ambivalent nature of radioresistance of rodents having different ecological specialization: wood mice (Apodemus uralensis Pallas 1811) and mole-voles (Ellobius talpinus Pallas 1770) to acute (laboratory experiment) and chronic (long-term inhabiting the East Ural Radioactive Trace - EURT) radiation action are presented. These species are greatly distinguished by a way of life, a migratory activity, an average life span etc. Numerous immunological, hematological disturbances were found in more radioresistant wood mice inhabiting in radioactively-polluted biogeocenosis (density of pollution 90Sr - 18.5 MBq/m2 = 500 Ci/km2). On the contrary there are no pathological shifts in more radiosensitive mole-voles from the EURT zone (density of pollution 90Sr - 37 MBq/m2 = 1000 Ci/km2). Comparative analysis of the hematological and immunological parameters and absorbed dose loads in rodents from radiocontaminated environment testify about the possibility of radioadaptation in a series of generations in Ellobius talpinus Pall. The leading role in development of radioadaptation of mole-voles belongs to ecophysiological peculiarities of the species. PMID- 17867508 TI - The clinical outcomes of three surgical managements on primary angle-closure glaucoma. AB - PURPOSE: To investigate the efficacy of trabeculectomy, phacotrabeculectomy and phacoemulsification in the management of primary angle closure glaucoma (PACG). METHODS: A prospective observational study was performed in 88 chronic PACG patients (97 eyes) who were divided into three groups following defined indications to receive different surgical interventions. The indications and clinical outcomes were evaluated. The mean follow-up was (17.7 +/- 4.9) months. RESULTS: Success rate in trabeculectomy, phacotrabeculectomy and phacoemulsification group was 81.08%, 78.57% per hundred and 81.25% per hundred, respectively. The anterior chamber depth was deeper and the angle was wider postoperatively vs. preoperatively both in phacotrabeculectomy and phacoemulsification group. No obvious changes were seen in trabeculectomy group. The coefficient of outflow facility of aqueous humor (C values) significantly increased in three groups postoperatively (P < 0.01). No severe intraoperative complications were found and the incidence of postoperative complications was low. Five eyes sustained hypotony 3 +/- 1.87 months in trabeculectomy group and 1 eye happened malignant glaucoma in phacotrabeculectomy group. The visual acuity in patients with phacotrabeculectomy plus intraocular lens implantation and those only with phacoemulsification plus intraocular lens implantation were improved 78.57% and 93.74%, respectively. No significant improvement was found in trabeculectomy group (chi2 = 47.10, P < 0.001). CONCLUSION: Three surgical interventions were beneficial to manage PACG and with co-existing cataract. The indication choosing was suggested according to visual acuity, angle closure circumference, cataract, medication requirements and optic nerve damage. Phacotrabeculectomy was recommended for angle closed > or =180 degrees circumference while phacoemulsification for angle closed <180 degrees. PMID- 17867509 TI - [Investigation on the mutation of MYOC gene in two family pedigrees with primary open-angle glaucoma in Shanxi]. AB - PURPOSE: To investigate the mutations of MYOC gene in two family pedigrees with primary open-angle glaucoma(POAG) in Shanxi. METHODS: Two POAG pedigrees in Shanxi were recruited and underwent complete ophthalmic examination. Genomic DNA was extracted from the peripheral blood of patients, of relatives and of normal controls. The coding sequence of MYOC gene was amplified by PCR with 7 pairs of primers. The PCR products were sequenced to screen for mutation sites. RESULT: In Pedigree 1, no MYOC mutations were observed. One missense MYOC mutation, Ser341Pro, was identified in Pedigree 2, but there was no mutation presented in unaffected relatives and normal controls. CONCLUSION: MYOC Ser341Pro mutation may be account for the POAG in the Pedigree 2. PMID- 17867510 TI - [The observation of visual quality after the implantation of apodized diffractive multifocal intraocular lens]. AB - OBJECTIVE: To obverse visual acuity, visual symptom and the rate of spectacle independence after implantation of a multifocal intraocular lens (MIOL) in patients with age related cataract. METHODS: Sixty patients (68 eyes) with age related cataract were enrolled in two groups. ReSTOR SA60D3 MIOL and Natural SN60AT monofocal intraocular lens were specially implanted after phacoemulsification. Uncorrected distance visual acuity (UCDVA), best-corrected distance visual acuity (BCDVA), uncorrected near visual acuity (UCNVA), best corrected near visual acuity (BCNVA), distance-corrected near vision acuity (DCNVA), visual symptom and the rate of spectacle independence were observed. RESULTS: UCDVA and BCDVA in multifocal group were not statistically different from those in monofocal group (P > 0.05). UCNVA and DCNVA were statistically better in multifocal group than in monofocal group (P < 0.05). The multifocal group has higher rate of spectacle independence than the monofocal group (73.3% versus 13.3%) (P < 0.05) when reading. The visual symptom such as glare and halo were more serious in multifocal group than in monofocal group (P < 0.05). CONCLUSIONS: Acrysof ReSTOR apodized diffractive multifocal intraocular lens may provide an excellent distance and near visual acuity, and decrease the dependence of spectacle. PMID- 17867511 TI - [The study of long-term curative effect of array multifocal intraocular lens after phacoemulsification]. AB - PURPOSE: To compare the long-term curative effect of multifocal intraocular lens Array (AMO) with conventional monofocal intraocular lens AcrySof (Alcon) on functional visual performance, and to evaluate the safety and the effectiveness of the multifocal intraocular lens. METHODS: 30 cases (60 eyes) after the phacoemulsification with IOL implantation were included. Patients presented for cataract surgery were randomized to receive either Array (AMO) intraocular lens or the AcrySof (Alcon). 15 cases (30 eyes) of multifocal intraocular lens implantation were enrolled at investigational sites. 15 cases (30 eyes) of monofocal intraocular lens implantation were enrolled in a control ground. All the patients were followed up for more than 3 months post operatively. Patients were examined uncorrected distant visual acuity (UCDVA), best corrected distant visual acuity (BCDVA), uncorrected near visual acuity (UCNVA), best corrected near visual acuity (BCNVA), contrast sensitivity (CS) in the best corrected. Contrast sensitivity testing served as the principal outcome measure. All of these people with ocular pathology other than other disease known to affect contrast sensitivity were excluded. All of these people were 50-80 years old. The contrast sensitivity function was measured by one person. RESULTS: There was no significant difference about BCDVA and BCNVA between two groups (P > 0.05). UCNVA and UCDVA in multifocal intraocular lens group were better than control group (P < 0.05). Postoperative contrast sensitivity testing revealed no statistical significance in 3CPD, 6CPD, 12CPD between two groups (P > 0.05). In 18 CPD, multifocal intraocular lens group were worse than control group (P < 0.05). CONCLUSIONS: Long term curative effect shows that multifocal intraocular lens can offer better visual sight.Contrast sensitivity in two groups has no difference except in 18 CPD. PMID- 17867512 TI - [Wavefront analysis in pseudophakic eyes by using allegretto wave analyzer]. AB - PURPOSE: To analyze the wavefront aberrations of pseudophakic eyes. METHODS: Seventy-eight patients (84 eyes) who have undergone phacoemulsification and Alcon Acrysof SA60AT intraocular lens were divided into 3 groups by the stage of post operation. Allegretto Wave Analyzer (Wavelight Laser Technologie AG, Germany) implanted into the eyes was applied to analyze the wavefront aberrations. Twenty three healthy normal eyes were involved in the control group. RESULTS: The higher order aberrations were detected in all the eyes (100%) of Group 1-3. The higher order aberration of Group 1 (the first week of post-operation) was RMSh (0.3774 +/- 0.2311) microm, which of Group 2 (the first month of post-operation) was RMSh (0.4782 +/- 0.395 2) microm, which of Group 3 (the third month of post-operation) was RMSh (0.2880 +/- 0.1522) microm. The higher order aberration of the control group was RMSh (0.3412 +/- 0.2048) microm. The difference of higher order aberration root mean square (RMSh) values between Group 3 and Group 2 has statistical significance (P < 0.05). But the differences of RMsh between the control group and Group 1, 2, 3 apart were no significant (P > 0.05). CONCLUSION: The higher order aberrations of pseudophakic eyes may be a reason why the visual qualities of phakic eyes are not better than those of normal human eyes statistically when their vision acuity is alike. The IOLs which can reduce higher order aberrations will improve the visual qualities of pseudophakic eyes. Ophthalmologists are looking forward to optimizing and designing individual intraocular lens. PMID- 17867513 TI - [Changes of corneal endothelium morphology and thickness after secondary intraocular lens implantation of traumatic aphakia]. AB - PURPOSE: To find out changes of corneal endothelium morphology and corneal thickness after secondary intraocular lens implantation of traumatic aphakia. METHODS: Twenty-one patients with traumatic aphakia were included in this study. According to the ocular presentation only two surgical methods were performed: secondary PMMA lens implantation through superior corneoscleral incision and transscleral fixation of PMMA intraocular lens with intraocular infusion. Photographs were taken at 5 points area of cornea, including central, superior, inferior, temporal, and nasal points. Endothelial density, area, variation and corneal thickness were measured before and after the operation. The changes of corneal endothelium and thickness after the operation were analysed. Factors that induced the changes were also discussed. RESULTS: (1) Twenty-one patients were included in this study. Eleven patients underwent the operation of PMMA lens implantation through superior corneoscleral incision, while ten patients underwent the operation of transscleral fixation of PMMA intraocular lens with intraocular infusion. The hexagonally of corneal endothelium decreased and cell variation increased in the superior cornea after the operation, but they both did not change in other places of cornea. The corneal thickness of patients without intraocular infusion and transscleral fixation did not change after the operation. But the corneal thickness of each corneal point of patients without intraocular infusion and transscleral increased equally after the operation. CONCLUSIONS: Corneal swelling occurred in patients undergoing transscleral fixation of PMMA intraocular lens with intraocular infusion. Intraocular infusion will temporally influence the function of corneal endothelium, which induces corneal swelling. Corneal endothelium is damaged mainly by surgical manipulation. PMID- 17867514 TI - [Ultraviolet B irradiation induces NF-kappaB activation and tumor necrosis factor alpha production in mouse cornea]. AB - PURPOSE: To evaluate the activation of nuclear factor-kappaB (NF-kappaB) and expression of tumor necrosis factor (TNF)-alpha in mouse cornea following different doses of ultraviolet-B (UVB) irradiation and to demonstrate the potential role of NF-kappaB in the corneal damage. METHODS: ICR mice were randomly divided into control group, mice irradiated by low dose (300 mJ/cm2) and high dose (1200 mJ/cm2) of UVB group. The mouse corneas were observed under a slit lamp microscope, and corneal opacity was graded to evaluate corneal damage. Then the mice were sacrificed at time points varying from 6 hours to 72 hours after treatment and then corneas were excised. Translocation of NF-kappaB was examined by electrophoretic mobility shift assay (EMSA). TNF-alpha production was measured by enzyme-linked immunosorbant assay (ELISA). Moreover, eyes were harvested for routine histological analysis and electron microscopy. RESULTS: Mild corneal edema was observed after low-dose of UVB irradiation, and resolved after 72 hours.However, significant and persistent corneal edema was observed after high dose of UVB irradiation. EMSA results showed that the marked increased activation of NF-kappaB after UVB irradiation, compared with the control group. The level of activity of NF-kappaB was enhanced as the radiant exposure increased. The significance was statistically different at each time point between groups. ELISA showed rapid production of high levels of TNF-alpha concomitant with the up-regulation of NF-kappaB. Histological findings by electron microscopy demonstrated only damage of corneal epithelial cell and superficial keratocytes in low-dose group. Ultrastructural morphology in high dose group showed deeper damage including keratocytes throughout the whole stroma and endothelial cells. CONCLUSIONS: These results suggest that acute ultraviolet exposure induces the activation of NF-kappaB which results in the production of proinflammatory cytokines such as TNF-alpha. Moreover, the up-regulated NF-KB activation was concomitant with the enhanced corneal damage. These findings imply that NF-kappaB may play an important role in the pathogenesis of UV-induced damage of cornea. PMID- 17867515 TI - Keratinocyte growth factor-2 on the proliferation of corneal epithelial stem cells in rabbit alkali burned cornea. AB - PURPOSE: To determine whether the topical application of keratinocyte growth factor-2 (KGF-2) can enhance corneal epithelial healing in rabbit alkali burned cornea. In addition, the distribution and proliferation of corneal epithelial stem cells in KGF-2-treated and control corneas were investigated to explain their mechanisms of effects on the epithelium. METHODS: Twenty-four New Zealand eyes were divided into four groups, treated with KGF-2 solution (1, 50, 100 microg/ml) and PBS solution. Eighth millimeter filter paper discs, produced by standard paper punch, were soaked for 15 sec in 0.5N NaOH solution. The alkali soaked discs were applied to the central cornea, centered on the pupil and held gently in position with forceps for 1 min. The cornea was finally irrigated over 1 mm with 100 ml balanced salt solution (BSS). Keratinocyte growth factor-2 was then applied topically three times a day. The phosphate-buffered saline (PBS) group was served as a control. Each corneal epithelial defect was subsequently photographed every 24 hours with a slit lamp and was measured by computer assisted digitizer. In each group, two rabbits were sacrificed for light microscopic examination after the interval of 7, 14 and 21 days. Meanwhile, the cornea epithelium was examined hy immunohistochemistry for P63, AE5, EGFR. RESULTS: Topical application of 10 microg/ml to 100 microg/ml KGF-2 significantly accelerated corneal epithelial wound healing when compared with controls. After 24 hours, epithelial healing rate of the 100 microg/ml KGF-2 group and the PBS treated group was (74 +/- 6)% and (40 +/- 8)% (P < 0.05). After 48 hours, the rate of the C group was (94 +/- 6)%, whereas in the control group it was (73 +/- 12)% (P < 0.05). Epithelial defects were often recurrent, which happened only two times in the 100 microg/ml KGF-2-treated group, but many times in the control group. In the corneal epithelial stem cell analysis, the number of the P63 positive cells was higher in the KGF-2-treated PMID- 17867516 TI - [An investigation on the causes of blindness and low vision of students in blind school in Guangzhou]. AB - PURPOSE: To determine the underlying causes of blindness and low vision, potentially preventable and treatable causes of the students in blind school in Guangzhou. METHODS: In 2004, students in Guangzhou Blind School were examined, and WHO Prevention of Blindness Program (WHO/ PBL) Eye Examination Record for children with blindness and low vision was used. RESULTS: Of the 177 students (4 33 years, 13.5 average), all were blind or visually impaired severely (visual acuity, V/A, less than 0.1 in the better eye). No light perception, V/A < 0.05 and visually impaired (V/A < 0.1) were 31.1%, 54.2% and 8.5% respectively, others refused to be examined or were mental retard. The causes were retinopathy of premature infant (ROP) (37.9%), optic nerve hypoplasia, Phthisis or cause unknown, retinal degeneration (8.5%), congenital glaucoma (5.1%), congenital macular abnormal (4.5%), retinal detachment (3.9%), congenital cataract (3.9%), microphthalmos (2.8%), corneal disease (2.8%) and other causes. ROP was the most important cause (37.9%), accounting for 57.7% cases in < or =10 years group, 33.9% in < or = 15-year group, 28.6% in < or = 20-year group, 14.3% in older than 20-year group; and 52.7% in no light perception group, 31.3% in V/A < 0.05 group 63.6% in incorporated and mental retard group. 73 cases (41.2%) were with avoidable blindness and visual impairment including ROP, refractive error and amblyopia after cataract surgery, V/A in 14 cases (7.9%) could be improved after treatment. CONCLUSIONS: Along with the improvement of health and socio-economic status, ROP become the major causes in children in recent years. Things remained to be done to eliminate childhood blindness. PMID- 17867517 TI - [Abnormal property of meibomian secretion and dry eye syndrome]. AB - PURPOSE: To study the relationship between meibomian secretion and dry eye. METHODS: To observe 68 outpatients (136 eyes) consecutively. Routine check up included vision, anterior segment and fundus, scoring of tear break up time (BUT), Schirmer I test and rose bengal staining (rb). Recorded the property of meibomian secretion. Defined the dry eye as mild and severe. RESULTS: Meibomian secretion was sorted as egg-white-like secretion (n=28), milk-yellowish secretion (n=26), granular secretion (n=30) and toothpaste-like secretion (n=52). The result declared that BUT and rb scoring stepped up consecutively in the above secretions, that was higher in toothpaste-like secretion than in other groups (all P < 0.01). Schirmer I scoring was below 1 in all groups, and there was no difference in the groups. Fifty-four eyes (40%) met the criteria of dry eye syndrome. The incidence of dry eye stepped up in groups as egg-white-like secretion (2/28) 7.1%, milk-yellowish secretion (4/26) 15%, granular secretion (8/30) 27% and toothpaste-like secretion (40/52) 77%. The incidence was higher in granular secretion than in egg-white-like secretion (P < 0.05), while the incidence was higher in toothpaste-like secretion than in any of other 3 groups (P < 0.01). There was no severe dry eye in egg-white-like secretion and milk yellowish secretion, while dry eye was found in 2 out of 8 in granular secretion, and in 19 out of 40 in toothpaste-like secretion. Incidence of severe dry eye was found higher in toothpaste-like secretion than in non toothpaste-like secretion (P < 0.05). CONCLUSION: Abnormal meibomian secretion affects the stability of ocular surface. The patients with toothpaste-like secretion are prone to dry eye and tend to have a worse dry eye than other secretion groups. PMID- 17867518 TI - Radiation retinopathy associated with central retinal vein occlusion. AB - PURPOSE: To report a case of radiation retinopathy associated with central retinal vein occlusion. METHODS: The clinical features and fundus fluorescein angiography of this case were analyzed. RESULTS: The patient had been treated with radiotherapy for her nasopharyngeal carcinoma, and presented with sudden visual loss in the left eye. The funduscopic examination and fluorescein angiography showed the features of radiation retinopathy in both eyes, and central retinal vein occlusion in the left eye. CONCLUSIONS: Radiation retinopathy can be associated with central retinal vein occlusion in the same eye, and it seems that the endothelial cell loss caused by radiation retinopathy may lead to retinal vein occlusion. PMID- 17867519 TI - Chaos, brain and divided consciousness. AB - Modern trends in psychology and cognitive neuroscience suggest that applications of nonlinear dynamics, chaos and self-organization seem to be particularly important for research of some fundamental problems regarding mind-brain relationship. Relevant problems among others are formations of memories during alterations of mental states and nature of a barrier that divides mental states, and leads to the process called dissociation. This process is related to a formation of groups of neurons which often synchronize their firing patterns in a unique spatial maner. Central theme of this study is the relationship between level of moving and oscilating mental processes and their neurophysiological substrate. This opens a question about principles of organization of conscious experiences and how these experiences arise in the brain. Chaotic self organization provides a unique theoretical and experimental tool for deeper understanding of dissociative phenomena and enables to study how dissociative phenomena can be linked to epileptiform discharges which are related to various forms of psychological and somatic manifestations. Organizing principles that constitute human consciousness and other mental phenomena from this point of view may be described by analysis and reconstruction of underlying dynamics of psychological or psychophysiological measures. These nonlinear methods in this study were used for analysis of characteristic changes in EEG and bilateral electrodermal activity (EDA) during reliving of dissociated traumatic and stressful memories and during psychopathological states. Analysis confirms a possible role of chaotic transitions in the processing of dissociated memory. Supportive finding for a possible chaotic process related to dissociation found in this study represent also significant relationship of dissociation, epileptiform discharges measured by typical psychopathological manifestations and characteristic laterality changes in bilateral EDA in patients with schizophrenia and depression. Increased level of psychopathological symptoms indicates close relationship to the right-left EDA asymmetry and asymmetry of information entropy calculated by non-linear recurrence quantification analysis of EDA records. Because epileptiform activity has specific chaotic behaviour and calculated information entropy from EDA records reflects the complexity of the deterministic structure in the system there is a relevant assumption that unilaterally increased complexity may produce interhemispheric disbalance and increased chaoticity which hypothetically may serve as a dynamic source of epileptiform discharges related to trauma induced kindling mechanism. Specific form of chaotic inner organization which cannot be explained only as a consequence of external causality support also psychophysiological data that lead to the so-called self organizing theory of dreaming by Kahn and Hobson. This study suggests that self organizing theory of dreaming is particularly important with respect to problem of memory formation and processing during dissociative states characteristic for dreams. Recent data and also findings of this study support the research utility of chaos theory in psychology and neuroscience, and also its conceptual view of dynamic ordering factors and self-organization underlying psychological processes and brain physiology. PMID- 17867520 TI - Deaths: final data for 2004. AB - OBJECTIVES: This report presents final 2004 data on U.S. deaths; death rates; life expectancy; infant and maternal mortality; and trends by selected characteristics such as age, sex, Hispanic origin, race, marital status, educational attainment, injury at work, state of residence, and cause of death. Previous reports presented preliminary mortality data for 2004 and summarized key findings in the final data for 2004. METHODS: This report presents descriptive tabulations of information reported on death certificates, which are completed by funeral directors, attending physicians, medical examiners, and coroners. The original records are filed in the state registration offices. Statistical information is compiled into a national database through the Vital Statistics Cooperative Program of the Centers for Disease Control and Prevention's National Center for Health Statistics (NCHS). Causes of death are processed in accordance with the International Classification of Diseases, Tenth Revision (ICD-10). RESULTS: In 2004, a total of 2,397,615 deaths were reported in the United States. The age-adjusted death rate was 800.8 deaths per 100,000 standard population, representing a decrease of 3.8 percent from the 2003 rate and a record low historical figure. Life expectancy at birth rose by 0.4 year to a record high of 77.8 years. Age-specific death rates decreased for all age groups. (The decrease for children aged 5-14 years was not statistically significant.) The 15 leading causes of death in 2004 remained the same as in 2003. Heart disease and cancer continued to be the leading and second leading causes of death, together accounting for over one-half of all deaths. In 2004, Alzheimer's disease surpassed and swapped positions with Influenza, relative to their previous placements in 2003. The infant mortality rate in 2004 was 6.79 per 1000 births. CONCLUSIONS: Generally, mortality patterns in 2004 were consistent with long-term trends. Life expectancy in 2004 increased again to a new record level. The age adjusted death rate declined to a record low historical figure. Although not statistically significant, the decrease in the infant mortality rate is typical of recent trends; except for 2002, the infant mortality rate has either decreased or remained level each successive year from 1958 to 2004. PMID- 17867521 TI - HPLC separation of enantiomers using chiral stationary phases. AB - During recent few years, separations of enantiomers have become one of the most important analytical tasks. Modern separation techniques, such as the chromatographic ones, represent a very powerful tool in this respect and nowadays they are commercially and widely used all over the world. The importance of enantioseparation must be emphasized, not just because of drugs, food additives, and pesticides, but also because of other compounds which affect our life. The use of direct chromatographic enantioseparation seems to be a suitable approach not just in the analytical but also the preparative scale. This paper is focused on the separation of enantiomers using the chiral stationary phase as one of the ways of how to perform direct chromatographic separation. PMID- 17867522 TI - [Naphthoquinones and their pharmacological properties]. AB - Naphthoquinones are wide-spread phenolic compounds in nature. They are products of bacterial and fungal as well as high-plants secondary metabolism. Juglone, lawsone, and plumbagin are the most widespread compounds. Naphthoquinones display very significant pharmacological properties--they are cytotoxic, they have significant antibacterial, antifungal, antiviral, insecticidal, anti inflammatory, and antipyretic properties. Pharmacological effects to cardiovascular and reproductive systems have been demonstrated too. The mechanism of their effect is highly large and complex--they bind to DNA and inhibit the processes of replication, interact with numerous proteins (enzymes) and disturb cell and mitochondrial membranes, interfere with electrons of the respiratory chain on mitochondrial membranes. Plants with naphthoquinone content are widely used in China and the countries of South America, where they are applied to malignant and parasitic diseases treatment. PMID- 17867523 TI - Variability of the essential oil from three sorts of Echinacea MOENCH genus during ontogenesis. AB - Variability of the essential oil from three sorts of Echinacea MOENCH genus during ontogenesis The content and quality of the essential oil in relation to the main ontogenetic stages of plants were studied in three various sorts of Echinacea genus. The comparison included Echinacea purpurea, Echinacea atrorubens, and Echinacea pallida. The differences in the content of the oil in different parts of plants and the abundance of individual oil constituents in oils from the sorts under study at the optimum stage of ripeness for harvest were evaluated as well. PMID- 17867524 TI - Fagopyrum esculentum in vitro. AB - Common buckwheat is a valuable source of the flavonoid rutin. Its in vitro culture was derived from a young seedling plant and the content of flavonoids in the callus culture was compared with their content in an intact plant. The optimal nutrient medium for the cultivation of the in vitro culture and for the production of flavonoids is Murashige and Skoog medium which contains, during the cultivation in the normal light regime, the growth regulators combination of 2,4 D 1 mg/l and kinetin 1 mg/l. PMID- 17867525 TI - [Thermoplastic granulation as an alternative method for the preparation of hydrophilic-lipophilic oral matriix tablets]. AB - The paper focuses on the formulation of HPMC K-matrix tablets by compression of granulates previously prepared by melt granulation. The model drug was theophylline monohydrate. Montanglycol wax was used as the solid lipid binder in a concentration of 10-20 %. With respect to the obtained results, thermoplastic granulation was found to ensure suitable porosity, flow, and particle size of the granulates. In both dissolution media (phosphate buffer pH 6.8 and artificial gastric juice pH 1.2), the release of the model drug is dependent on the HPMC viscosity grade used. The release rate can be modified by a change in the HPMC-to montanglycol wax ratio. A decrease in this ratio increases the liberation of theophylline monohydrate. Due to different drug solubilities in the selected dissolution media, theophylline is released significantly faster in phosphate buffer pH 6.8 then in artificial gastric juice pH 1.2. The matrices of the same composition were prepared by direct compression; the comparison of dissolution profiles shows that the release of the active substance is not influenced by the employed method of manufacture. PMID- 17867526 TI - [Examination of the antioxidative and antidiabetic effect of pomiferin in alloxan induced diabetes mellitus in an experiment (a pilot study)]. AB - The antioxidative and antidiabetic effect of pomiferin was monitored under the experimental conditions of alloxan-induced diabetes mellitus. The animals were divided by random selection into 2 groups (n=7). The treated group was administered pomiferin in peroral doses of 10 mg/kg in Avicel, the placebo group was given only a solution of Avicel, and the last group was intact. Selected laboratory parameters (glucose, urea, cholesterol, antioxidative enzymes, total antioxidative capacity, malondialdehyde in serum: diuresis, total glucose and protein losses through urine) were determined. Kidney tissue and pancreas samples were taken for histopathological analysis. The findings included a statistically significant decrease (p < or = 0.01) in blood glucose level, a significant increase (p < or = 0.01) in glutathione peroxidase, total antioxidative capacity (p < or = 0.05) and a significant decrease (p < or = 0.01) in malondialdehyde level in the treated group compared to the placebo group. A highly significant decrease (p < or = 0.01) in diuresis, glucose and protein losses through urine were identified in the treated group compared to the placebo group. The superoxide dismutase catalytic activity, urea and cholesterol levels involved nonsignificant changes. The results of biochemical examination show a protective antioxidative and antidiabetic effect of pomiferin. The results of histopathological examination correlate with them only partially. PMID- 17867527 TI - [Chitosan in topical preparations]. AB - Chitosan in topical preparations Within the framework of experimental work at the Department of Pharmaceutical Technology of Slovak Medical University, "insect" chitin obtained from the buff-tailed bumblebee (Bombus terrestris) was processed to produce dosage forms and compared with commercially available chitin, or chitosan, obtained from shrimps (Pandalus borealus). The paper aimed to find whether insect chitin, or chitosan, possessed similar technological properties as commercially available and for topical preparations used products. Samples were prepared containing chitin, or chitosan, of different origin, 0.25 and 0.5% in a gel base. In some gels the gel base was acidified with citric acid (in an amount of 0.75%) or lactic acid (1%) to improve the mechanical properties of foils. All samples were well applicable and after drying a relatively resistant transparent layer was formed on the skin. All samples could be made to produce elastic foils, which after moistening clung well to the skin. Both chitin and chitosan obtained from the bodies of buff-tailed bumblebees differed from reference materials obtained from shrimps by the degree of deacetylation, possessed different technological properties, e.g., finer fibres, were more fragile, and when wet, they could be disintegrated better, which is obvious also from the results of microscopic evaluation. Chitosan prepared from chitin SAV (insect) possessed substantially finer particles in the dosage form. The evaluation of the flow properties of the prepared samples revealed that except Sample I (gel base alone) they are time-dependent tixotropic systems. Whereas chitin gels did not show any antimicrobial effect (which is apparently connected with bad solubility of chitin), gels with chitosan showed this activity. A more marked effect was observed in the strains of Staphylococcus aureus and Pseudomonas aeruginosa, and in Escherichia coli it was weaker. The paper reports the first tentative results of comparisons of chitin- and chitosan-containing gels obtained from insects and those obtained from shrimps, showing that the prepared samples were of comparable quality. PMID- 17867528 TI - [Medicinal preparations in a manuscript of a fifteen-century Franciscan monk in Brno]. AB - Medicinal preparations in a manuscript of a fifteen-century Franciscan monk in Brno An unknown Franciscan monk, who worked in his monastery's apothecary in Brno at the beginning of the 15th century, translated many extracts from Ancient and medieval authors into Czech. The collection, supplemented perhaps also from other manuscripts, contains a number of articles on treatment. It was repeatedly copied and has been preserved in several variants. The collection lists about two hundred medicinal preparations and many other pieces of advice and recommendations, mainly based on folk wisdom and knowledge. The most frequently listed items are aromatic waters, electuaries, potions, ointments, and plasters. The paper deals primarily with the technologies of their preparation and documents them by examples from the text of the collection. The collection includes also a herbarium. Some parts of the collection are markedly similar to other Czech manuscripts. PMID- 17867529 TI - The simultaneous analysis of proteins, lipids, and diterpenoid resins found in cultural objects. AB - We report a GC-MS method for the simultaneous analysis of proteins oil, and diterpenoid resins found in cultural objects. The method was initially designed for protein analysis of protenaceous paints and adhesives and involves acid hydrolysis as the first step. The amino acids in the protein hydrolysates, thus obtained, are treated with propan-l-ol/ hydrogen chloride and then pentafluoropropionic anhydride. The procedure was found also to yield the propyl esters of fatty acids derived from lipids and diterpenoid acids derived from natural resins, and thus allows the choice of a single method for the analysis of artists media which contain either oil s or proteins or mixtures of both proteins and oils or even resins. Thus natural mixtures such as egg yolk and also mixtures made by the artist such as animal glue/seed oil emulsions can be analysed. Coupled with FTIR analysis of paints and the staining of cross sections, to indicate layer structure the method can help to elucidate the paints and adhesives used by artists. PMID- 17867530 TI - Application of a portable XRF spectrometer for the non-invasive analysis of museum metal artefacts. AB - The present paper reviews examples of the application of a portable - in house developed- XRF spectrometer for the analysis of museum metal artefacts in Greece. Specific topics are addressed, in particular, to which extent the qualitative or quantitative XRF analyses reveal important information about the raw materials and manufacture techniques used for gold, silver and bronze alloys in antiquity. The analytical information that it is gained by means of the XRF measurements is further assessed in comparison with the existing archaeometallurgical knowledge. PMID- 17867531 TI - Analysis of frankincense in archaeological samples by gas chromatography-mass spectrometry. AB - Four archaeological samples, unearthed from Qana in Yemen were analysed by analytical technique, currently applied in the field of petroleum geochemistry, and by gas chromatography coupled with a mass spectrometer (GC-MS). Sample no 1286 comes from a burned warehouse and samples no 964, 963 and 962 from the central sanctuary. These specimens were probably exposed to a heating source. In each case olibanum resin was identified according to the presence of their chemical markers corresponding to alpha- , beta-boswellic and lupeolic acids (3alpha-hydroxy-olean-12-en-24-oic, 3alpha-hydroxy-urs-12-en-24-oic and 3alpha hydroxy-lup-20(29)en-24-oic acids) and their respective O-acetyled derivatives (3alpha- O-acetyl-olean-12-en-24-oic, 3alpha-O-acetyl-urs-12-en-24-oic and 3-O acetyl-lup-20(29)-en-24-oic acids). Concerning the thermal degradation state of samples, the GC-MS results are in agreement with the geochemical ones. Sample no 1286 and 964 correspond to ageing incense which has not undergone any heating action and are consequently relatively well preserved. Lastly, samples no 963 and 962 are thermally degraded resins and their gross composition data permits to conclude that sample no 963 is only partially burnt while sample no 962 has been much more degraded. PMID- 17867532 TI - The Russian avant-garde painting palette--documentary and physicochemical study of inorganic colorants. AB - In the present article an attempt is being made to elucidate the inorganic colorants encountered in the Russian avant-garde painting palette by a combined art historical, documentary and physicochemical investigation; and to examine the influence of environmental factors on the chromatic profile originally sought by the artist. The overall approach based on written sources is confirmed by measurements on representative paintings from the Costakis Collection in the State Museum for Contemporary Art, Thessaloniki. The documentary research deals with the influences of Orthodox iconography, folkloric art, and occidental modernist tendencies on the Russian avant-garde palette; and is studying the effects of contradictory historical processes in the chromatic profile of individual paintings. In the experimental section a series of colorants are investigated concerning the effects of accelerated ageing on experimental painting tables, prepared as watercolour and gouache layers on paper ground. The resulting samples are subject to colorimetric, and spectroscopic measurements; and analogous analytical procedures are applied on samples taken from selected paintings belonging to the Costakis Collection. A systematic comparative study of all data permits evaluating the materials used as to their stability towards exstrincic factors, and proposing degradation routes, in order to assist museum curators and conservators in every concrete case related to the broad spectrum of pigments examined. PMID- 17867533 TI - Energy dispersive X-ray diffraction potentiality in the field of cultural heritage: simultaneous structural and elemental analysis of various artefacts. AB - The applicability of an Energy Dispersive X-ray Diffractometer to some technical questions in the field of Cultural Heritage is presented. This diffractometer, equipped with a white source, has been utilized for the structural and elemental analysis of some items having different nature. Given its design, the instrument allows to collect data from samples as big as a book or a little more. Samples, without collection of any portion and without any preliminary preparation, have been placed in the instrument and spectra have been collected in a wide energy range that contains X-ray fluorescence and diffraction features. In all cases, data acquired in air and in a non destructive way were reliable and their collection was fast. Fluorescence and X-ray diffraction information, when possible, have been compared with those obtained by XRF micro-analysis and by an Angle Dispersive X-ray Diffractometer equipped with a Cu X-ray source. By using the last two techniques, data have been collected from small areas of the samples. PMID- 17867534 TI - Infrared and Raman vibrational spectroscopies reveal the palette of frescos found in the medieval monastery of Karaach Teke. AB - Vibrational spectroscopy is applied on samples obtained from the excavation area of the medieval Monastery (10th century) of Karaach-Teke in Bulgaria. The results of the corresponding study, reveal the type of materials used for the creation of the wall-paintings and give evidence of Byzantine influence, a fact that further supports the well known impact of Byzantium on the technology and thematic aesthetic features of iconography in Bulgaria during this era. In addition, the complementarity of FTIR and micro-Raman spectroscopies in the identification of pigments is indicated. PMID- 17867535 TI - Large sample neutron activation analysis: a challenge in cultural heritage studies. AB - Large sample neutron activation analysis compliments and significantly extends the analytical tools available for cultural heritage and authentication studies providing unique applications of non-destructive, multi-element analysis of materials that are too precious to damage for sampling purposes, representative sampling of heterogeneous materials or even analysis of whole objects. In this work, correction factors for neutron self-shielding, gamma-ray attenuation and volume distribution of the activity in large volume samples composed of iron and ceramic material were derived. Moreover, the effect of inhomogeneity on the accuracy of the technique was examined. PMID- 17867536 TI - Studies in organic archaeometry VII--differentiation of wood and bark pitches by pyrolysis capillary gas chromatography (PY-CGC). AB - Tars and pitches were prepared from wood and bark of various deciduous trees and conifers and analysed with the intention to distinguish between various starting materials. All this was done before the background of an archaeometrical problem: to provide a basis for the chemical identification of those pitches which are frequently found in archaeological excavations. Intending to extend the already existing possibilities for such analyses the present paper is dealing with the application of pyrolysis coupled with capillary gas chromatography and by subsequent chemometric studies. It could be shown that by this technique indeed not only tars and pitches prepared from deciduous trees and from conifers could clearly be differentiated, but that even respective species could be identified. Thus a fundament is provided for future studies aiming to identify the starting material of real archaeological finds by a novel method which requires by far less quantities of sample material as compared to the methods hitherto used by us. PMID- 17867537 TI - Effect of selected natural dyes in reduction on colour changes of Egyptian linen textiles by fungi. AB - Linen is the most historical Egyptian textile fibre liable to fungal deterioration. Fungal deterioration of dyed linen textiles may appear as undesirable different stains. In order to success in removing of fungal stains from biodeteriorated historical Egyptian dyed linen textiles, it is necessary to understand the nature and causes of these stains, hence their subsequent removal. So this paper aims to investigate the effect of fungi on dyed linen textiles. In this study linen textile samples were experimentally dyed by two different dyes, blue one as an example to vat dye and yellow one as an example to direct dye. This work is done on two of the most important dyes (Turmeric and indigo), which were popular in most of historical periods in Egypt. Dyed linen samples were experimentally biodegraded by thirty different fungal strains isolated previously from historical Egyptian linen samples. The produced change in colours of the biodeteriorated samples was detected visually. Also, the change in reflection spectra and colour differences produced to dyed linen textiles after fungal deterioration, were assessed and evaluated by using spectrophotometer. This study reported that most of tested fungi contribute to discoloration of all tested dyed linen samples. These results indicate that most of stains on historical Egyptian dyed linen textiles, may be fungal stains. The results confirm that undyed linen textiles more liable to fungal biodeterioration than dyed ones. Also the results show that yellow dyed linen textiles are more susceptible to fungal deterioration than blue dyed linen textiles. The obtained results show that Alternaria tenuissima, Chaetomium globosum, Chaetomium sp., Penicillium raistrickii, P. soppi, P. asperum, P. citrinum, Aspergillus carbonarius, A. fischeri, A. nidulans, A. terreus and A. niger, had showed the maximum colour changes of the deteriorated yellow dyed linen samples. The results also show that Alternaria tenuissima, Chaetomium sp., Penicillium asperum, P. citrinum, Aspergillus nidulans and A. spinulosus, had shown the maximum colour changes of the deteriorated blue dyed linen samples. PMID- 17867538 TI - Provenance determination of Vinica terra cotta icons using self-organising maps. AB - In the Vinica Fortress, Republic of Macedonia, 50 undamaged terra cotta icons and 100 fragments, all dated 6th-7th century, were found. In order to determine the provenance of these unique terra cotta icons, the mass fractions of 19 different chemical elements were previously determined in ten fragments of the terra cotta icons and thirty three samples of clays from eight different sites from the region. Due to the dimensionality and complexity of the experimental data, the archaeometric results were treated with self-organising maps (SOM). The results obtained using SOM were compared with the ones obtained using principal component analysis. Both chemometric methods revealed that Vinica terra cotta icons were made from clay from Grncarka, 2.5 km South-East from the Vinica Fortress. PMID- 17867539 TI - Metallographic approach to the investigation of metallic archaeological objects. AB - Metallic objects are considered among the most significant findings in Cultural Heritage and represent the 'culture of Materials' and the habits of an historical period and of a population. They also preserve traces of time: from the transformation of the ores in metal (by smelting) to the degradation from metal to oxidised compounds (by corrosion processes). Metallography, historically devoted to connect the microstructural features to production processes and to chemical-physical-mechanical properties is a powerful and relatively easy approach to characterise metallic findings. All analytical tools and methods in the hands of a metallographer are improved through experience and practice and provide a large number of information (elemental composition, primary and secondary microstructures, surface treatments, corrosion rate, original ores traces) by the preparation of a fairly small microdestructive sample. A wise and careful use of the metallography allows the balance "object sacrifice/knowledge improvement" to lean on the right side contributing to the hard work of rebuilding humankind history. Beside a description of a research protocol some practical examples concerning archaeological findings are presented in this paper. PMID- 17867540 TI - Filler segmentation of SEM paper images based on mathematical morphology. AB - Recent developments in microscopy and image processing have made digital measurements on high-resolution images of fibrous materials possible. This helps to gain a better understanding of the structure and other properties of the material at micro level. In this paper SEM image segmentation based on mathematical morphology is proposed. In fact, paper models images (Whatman, Murillo, Watercolor, Newsprint paper) selected in the context of the Euro Mediterranean PaperTech Project have different distributions of fibers and fillers, caused by the presence of SiAl and CaCO3 particles. It is a microscopy challenge to make filler particles in the sheet distinguishable from the other components of the paper surface. This objectif is reached here by using switable strutural elements and mathematical morphology operators. PMID- 17867541 TI - Re-examination of Turkey red. AB - Cotton yarn was dyed in Turkey red using madder through a special method. Amount of the dyestuffs bound to mordanted cotton fibre and the oiling numbers of the cotton yarn was investigated by using TLC (thin layer chromatography) and spectrophotometry. Sn(II) in the bright red cotton yarn was analysed by X-ray diffraction method. PMID- 17867542 TI - A long time coming. PMID- 17867543 TI - Piezoelectric osteotomies for outpatient rapid palatal expansion. PMID- 17867544 TI - Surgical intervention of complex endo-perio lesions. AB - Complex endo-perio lesions are infrequent, but pose treatment dilemmas. The lesions are complex with bone loss involving adjacent teeth that are not part of the initial endodontic lesion. The aggressive bone loss is not clearly understood and apparently has some differences from the usual apical periodontitis. PMID- 17867545 TI - Sympathetically maintained pain presenting first as temporomandibular disorder, then as parotid dysfunction. AB - Complex regional pain syndrome (CRPS) is a chronic condition that usually affects extremities, such as the arms or legs. It is characterized by intense pain, swelling, redness, hypersensitivity in a region not defined by a single peripheral nerve and additional sudomotor effects, such as excessive sweating. The clinical criteria for the diagnosis of sympathetically maintained pain as outlined by the International Association for the Study of Pain include: Onset following an initiating noxious event (CRPS-type I) or nerve injury (CRPS-type II). Spontaneous allodynia that is not limited to peripheral nerve distribution and is not proportionate to the inciting event; abnormal sudomotor activity, skin blood flow abnormality, edema, other autonomic symptoms; and exclusion of other conditions that may otherwise contribute to the extent of the symptoms. Only 13 cases of CRPS involving sympathetically maintained pain in the head and neck region have been described, and all reported trauma as the identifiable etiologic factor. The case presented here is another occurrence of sympathetically maintained pain in the head and neck region, but without nerve injury as a clear initiating factor. PMID- 17867546 TI - Oral and maxillofacial pathology case of the month. Angiocentric T-Cell lymphoma (midline lethal granuloma). PMID- 17867547 TI - Biosynthesis and biological activity of enniatins. AB - Enniatins are N-methylated cyclohexadepsipeptides (CHDPs), composed of three units each of N-methylated branched-chain L-amino acid and D-2-hydroxy acid arranged in an alternate fashion. These low-molecular secondary metabolites are produced by Fusarium species, typical mycotoxin producing fungi. Enniatins are known for their ionophoric, phytotoxic and anthelmintic effect, antibiotic activity and recently their potent cytotoxic activity against cancer cell lines was shown. They act also as inhibitors of drug efflux pumps. Biosynthesis, biological activity, and the structural characteristics of these microbial metabolites were summarized in this review. PMID- 17867548 TI - Creation of a novel cell penetrating peptide, using a random 18mer peptides library. AB - Cell penetrating peptides (CPPs) have drawn attention as carriers for intracellular drug delivery. It is commonly believed that TAT peptide is the best carrier among the existing CPPs due to its high translocational activity. Despite considerable research, the cellular uptake mechanism of TAT peptide remains unclear. Additionally, the transduction efficiency of TAT peptide is insufficient for use in intracellular therapy. In this study, we attempted to identify novel CPPs from a random 18mer peptide library using a phage display system. To isolate novel CPPs more effectively, PSIF (protein synthesis inhibition factor) was used with the screening system. Consequently, we isolated 7 novel CPPs from the library and determined by flow cytometry and confocal laser microscopy that these CPPs were taken up into cells. Once the cellular uptake pathway of these CPPs has been determined, it may be possible to use them for intracellular therapy. PMID- 17867549 TI - Species-dependent plasma metabolism of the ester compound daidzein 7,4'di succinic acid mon-ester-O-ethoxy (DZ5). AB - Daidzein 7,4'di-succinic acid mon-ester-O-ethoxy (DZ5) is an ester-containing compound, which was recently synthesized. The objective of this study was to determine the hydrolysis rate of DZ5 in blood from the rat and the dog. The data showed that the hydrolysis rate of DZ5 in plasma was much more rapid in rats than in dogs following intravenous administration. Moreover, similar results were observed after in vitro incubation of DZ5 in the rat or dog plasma. The findings suggested that plasma esterases in the rat plasma have higher activity than in the dog and plasma metabolism of DZ5 is species-dependent. PMID- 17867550 TI - Development and validation of an accurate HPLC method for the quantitative determination of picroside II in tablets. AB - A simple, sensitive and accurate high performance liquid chromatographic method (HPLC) with UV detection was developed and validated to determine picroside II in a new tablet formulation with paeoniflorin as internal standard. Chromatographic separation was achieved on an Agilent XDB C18 column (250 x 4.6 mm I.D., 5 microm) using a mobile phase consisting of acetonitrile-water-acetic acid (18:82:0.4, v/v/v) at a flow rate of 1.0 ml/min. The UV detection wavelength was set at 265 nm. Linear calibration curves were obtained in the concentration range of 0.10-100 microg/ml with the limit of quantification (LOQ) of 0.10 microg/ml. The within- and between-run precisions in terms of % relative standard deviation (RSD) were lower than 5.7% and 6.3%, respectively. The accuracy in terms of % relative error (RE) ranged from -2.3% to 5.0%. This validated method was successfully applied to the determination of the content of picroside II in a new tablet formulation. PMID- 17867551 TI - Pioglitazone impurities. AB - Methods of preparation of API pioglitazone were discussed from the point of view of impurities occurrence. Four real impurities (I-IV) of pioglitazone were prepared and characterized by means of NMR spectroscopy. PMID- 17867552 TI - Separation of beta-receptor blockers and analogs by capillary liquid chromatography (CLC) and pressurized capillary electrochromatography (pCEC) using a vancomycin chiral stationary phase column. AB - Enantiomeric separation of chiral pharmaceuticals was carried out by means of in capillary liquid chromatography (CLC) and pressurized capillary electrochromatography (pCEC) using a vancomycin chiral stationary phase (CSP). A 100 microm I.D. fused-silica capillary was packed with 5 microm diameter silica particles modified with vancomycin. Enantiomeric resolution of fifteen beta3 receptor blockers and analogs was studied by polar organic CLC mode and reversed phase pCEC mode using mobile phases containing methanol-isopropanol-acetic acid triethylamine and TEAA buffer-methanol, respectively. Several factors affecting chiral separation were investigated in both CLC and pCEC mode. Good enantiomeric resolution was achieved by CLC mode for propranolol, celiprolol, esmolol, bisoprolol, atenolol, metoprolol and carteolol using methanol-isopropanol-acetic acid-triethylamine (70:30:0.05:0.05, v/v/v/v) as mobile phase and for clenbuterol, bambuterol, terbutaline, and salbutamol using methanol-isopropanol acetic acid-triethylamine (50:50:0.05:005 or 50:50: 0.025:0.05, v/v/v/v) as mobile phase. The baseline was achieved by pCEC mode for the separation of esmolol, bisoprolol, atenolol, metoprolol, carteolol in the mobile phase containing MeOH-0.05%TEAA (pH 7.0) (90:10, v/v) (-10 kV), and that of propranolol and celiprolol in the mobile phase containing MeOH-0.025%TEAA (pH 7.0) (90:10, v/v)(-10 kV). Comparative enantioseparations performed in polar organic CLC and reversed phase pCEC mode revealed significant difference. PMID- 17867553 TI - Simultaneous identification and quantification by liquid chromatography of benzethonium chloride, methyl paraben and triclosan in commercial products labeled as grapefruit seed extract. AB - A HPLC method has been developed which permits the quantification of methyl paraben, benzethonium chloride and triclosan in various samples of grapefruit seed extract (GSE). The best results were obtained with a Phenomenex Gemini C18 column using gradient mobile phase of water (0.1% acetic acid) and acetonitrile (0.1% acetic acid) with a flow rate of 1.0 mL per minute. The detection wavelength was 254 nm for methyl paraben, and 275 nm for benzethonium chloride and triclosan. The main synthetic antimicrobial agent identified in commercial GSE samples was benzethonium chloride in concentrations from 0.29-21.84%. Positive ion electrospray MS of a commercial GSE sample showed a molecular ion at m/z 412 [M+], which matched that of a standard of benzethonium chloride. Triclosan was detected in two samples at 0.009 and 1.13%concentrations; while methyl paraben was not detected in the samples analyzed. PMID- 17867554 TI - Development and validation of a spectrophotometric method for estimation of letrozole in bulk and pharmaceutical formulation. AB - A simple, sensitive and accurate UV spectrophotometric method has been developed for the determination of letrozole, a new aromatase inhibitor, in raw material and tablets. The drug shows maximum absorption at 238 nm. Beer's law was obeyed in the concentration range 2-20 microg/mL for the drug. Results were validated statistically according to ICH guidelines. Validation of the method yielded good results concerning range, linearity, precision and accuracy. It was found that the excipients present in the commercial formulation did not interfere with the method. PMID- 17867555 TI - Solid dispersion of spironolactone with porous silica prepared by the solvent method. AB - Solid dispersions of spironolactone (SPI) with porous silica (Sylysia 730 and Sylysia 350) were prepared by the solvent method. The physicochemical properties of the prepared solid dispersions were evaluated by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and atomic force microscopy (AFM). In the SEM study, no differences in the surface condition between Sylysia 350 and the solid dispersion of a Sylysia 350:SPI system in a weight ratio of 1:1 were observed. However, AFM phase images showed that the surface of the solid dispersion of the Sylysia 350:SPI system (weight ratio of 1:1) was rather smooth due to the adsorption of SPI as compared with that of a Sylysia 350 intact. The results of PXRD and DSC data in the solid dispersion of the Sylysia 350:SPI system (weight ratio of 1:1) indicated that the molecular state of the adsorbed SPI changed from crystalline to amorphous. Although the decrease in the SPI concentration increased with the amorphous fraction in the solid dispersion, the diffraction peaks due to SPI crystals still remained in the solid dispersion of a Sylysia 730:SPI system (weight ratio of 1:1), indicating that the mean pore diameter and specific surface area of an additive are some of the important factors for the amorphization of SPI crystals. The dissolution property of the SPI from the solid dispersions was remarkably improved in comparison with that of SPI crystals. The dissolution rate of the SPI from the solid dispersions with Sylysia 350 was faster than that of the SPI from the solid dispersions with Sylysia 730. The difference in the dissolution properties of SPI from both the solid dispersions was attributed to the difference in the molecular state of the SPI in both the solid dispersions. In the stability test, the amorphous state of the SPI in the solid dispersion of the Sylysia 350:SPI system (weight ratio of 1:1) was maintained for 2 weeks at 25 degrees C and 0% RH, while the amorphous SPI without Sylysia 350 crystallized under the same conditions. PMID- 17867557 TI - Effect of the spin-labelled 1-ethyl-1-nitrosourea on CCNU-induced oxidative liver injury. AB - This study was carried out to determine the effects of 1-ethyl-3-[4-(2,2,6,6 tetramethylpiperidine-1-oxyl)]-l-nitrosourea (SLENU), recently synthesised in our laboratory, and vitamin E as positive control on 1-(2-chloroethyl)-3-cyclohexyl-1 nitrosourea (CCNU) - free radical induced oxidative injuries in the liver of mice. Specifically, alterations in malonyl dialdehyde (MDA) level and activities of some antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT), were measured in liver homogenates from tumour-bearing C57 black mice after treatment with solutions of CCNU (30 mg/kg) and SLENU (100 mg/kg), both administered intraperitoneally. CCNU-induced increase in MDA level, SOD and CAT activities were suppressed by SLENU. The present results and those from a previous report demonstrated superoxide scavenging activities (SSA) of the nitrosourea SLENU and enabled us explain the protective effect of the spin-labelled nitrosourea on CCNU induced oxidative stress in the liver of mice. This protective effect is through the scavenging of *O2- and by an increased production of *NO. Thus, a potential for developing new combination chemotherapy in cancer is seen. PMID- 17867556 TI - Enhancement of bioavailability and anthelmintic efficacy of albendazole by solid dispersion and cyclodextrin complexation techniques. AB - The objective of this study was to improve the oral bioavailability and therapeutic efficacy of albendazole (ABZ) employing solid dispersion and cyclodextrin complexation techniques. Solid dispersion (dispersion) was prepared using ABZ and polyvinylpyrrolidone (PVP) polymer (1:1 weight ratio). Ternary inclusion complex (ternary complex) was prepared using ABZ, hydroxypropyl beta cyclodextrin (HPbetaCD) and L-tartaric acid (1:1:1 molar ratio). In rabbits with high gastric acidity (gastric pH approximately 1), ternary complex and solid dispersion showed a bioavailability enhancement of 3.2 and 2.4 fold respectively, compared to a commercial suspension (p < 0.05). The rise in gastric pH (pH > 5) caused a 62% reduction in AUC (area under the plasma level curve) for the commercial suspension, whereas the reduction in case of PVP dispersion and ternary complex was only 43% and 37% respectively. The rapid absorption of the drug from solid dispersion and ternary complex was reflected in improved anthelmintic efficacy against the systemic phases of Trichinella spiralis. The ternary complex was significantly more efficient than solid dispersion and exhibited the highest larvicidal activity (90%) at a dose of 50 mg x kg(-1) (p < 0.05). These results suggest that the bioavailability and therapeutic efficacy of the ternary complex might be high even if there is a great variation in the gastric pH. PMID- 17867558 TI - Preparation, characterization and uptake by primary cultured rat hepatocytes of liposomes surface-modified with glycyrrhetinic acid. AB - 3-succinyl-30-stearyl glycyrrhetinic acid (Suc-GLAOSt) was synthesized as a targeting molecule, and incorporated in ordinary to liposomes (LP) to prepare a liposome surface-modified with glycyrrhetinic acid (LP-GLA), which could bind to the hepatocyte through the specific binding site of glycyrrhetinic acid (GLA) on the surface of rat cellular membrane. The maximal molar ratio of Suc-GLAOSt to total lipids in LP-GLA was 1:10. Calcein loaded liposome (Cal-LP) and calcein loaded LP-GLA (Cal-LP-GLA) were prepared by an ethanol injection method. The average diameter of Cal-LP and Cal-LP-GLA was 65 nm +/- 16 nm and 68 nm +/- 21 nm, respectively. The characteristics of cellular uptake of the two types of liposome were investigated through cellular uptake and competitive inhibition experiments. The uptake of Cal-LP-GLA by rat hepatocytes was markedly higher (3.3 fold) than that of Cal-LP (P < 0.01). The uptake of Cal-LP-GLA was inhibited, but the uptake of Cal-LP was not influenced by adding extraneous GLA. LP-GLA may be internalized by hepatocytes via the specific binding site, and can be used as a novel and promising carrier for targeting drug delivery to hepatocytes. PMID- 17867559 TI - A novel effect of lobeline on vascular smooth muscle cell: inhibition of proliferation induced by endothelin-1. AB - Lobeline has a long history of therapeutic use ranging from an emetic and respiratory stimulant to a tobacco smoking cessation agent. Lobelia chinensis Lour, a traditional Chinese herb whose active ingredient is the alkaloid lobeline, demonstrated to antagonize the bioactive effect of endothelin-1 (ET-1) and prevent the proliferation of vascular smooth muscle cells (VSMCs) in hyperlipidemic rats. The objective of the present study was to determine the effects of lobeline on proliferation of cultured human umbilical VSMCs induced by ET-1. The results showed that the increased cell numbers and enhanced [3H]thymidine incorporation induced by ET-1 were inhibited and the transition of cells from static phase (G0/G1) to DNA synthesis (S) and mitotic phase (G2/M) was held back by lobeline in a concentration-dependent manner. Confocal microscopy demonstrated that lobeline markedly decreased the fluorescent intensity of intracellular Ca2+ concentration ([Ca2+]i) with a significant difference from ET group. Cytotoxicity was determined by Trypan blue exclusion. These results demonstrated a novel biological role of lobeline. Lobeline inhibited the proliferation of human umbilical VSMCs induced by ET-1 in a dose-dependent manner and the anti-proliferative effect was involved in the reduce of increased [Ca2+]i, rather than nonspecific cytotoxicity. PMID- 17867560 TI - Studies on the flavonoid substrates of human UDP-glucuronosyl transferase (UGT) 2B7. AB - Flavonoids are found in fruits, vegetables, nuts, seeds, herbs, spices, stems and flowers, as well as in tea and red wine. They are prominent components of citrus fruits and other food sources, are consumed regularly with the human diet, and have been shown to have many biological functions, including antioxidant and chelating properties. This study suggests features of the flavonoid structure necessary for it to act as a substrate of human UGT2B7. Generally speaking, flavonol has higher glucuronidation activity than flavones and isoflavones. Differences in C3' position have an important effect on UGT2B7 glucuronidation activity, and the various substituents have different influences on glucuronidation activity. For flavonol, the bulky group at C4' can enhance glucuronidation activity. Increasing the number of hydroxyl groups of flavonoids will increase their glucuronidation activity towards UGT2B7, while conjugation of glycon will weaken the activity, and hydroxyl position can also have an important role in activity. The high glucuronidation efficiency observed with many flavonoids suggests that the contribution of UGT2B7 to the metabolism of flavonoids may be significant. The results suggest that we should not only pay attention to glucuronidation activity, but should also attach importance to the regioselectivity of glucuronidation. PMID- 17867561 TI - Antihyperglycemic activity of Arbutus unedo, Ammoides pusilla and Thymelaea hirsuta. AB - The effect of the water extract (WE) of three medicinal plants used as antidiabetic medication in Eastern Morocco (Arbutus unedo: Au, Ammoides pusilla: Ap and Thymelaea hirsuta: Th) was tested in rats with the Oral Glucose Tolerance Test (OGTT) and Intravenous Glucose Tolerance Test (IVGTT). In the OGTT the rats received water, glibenclamide (2 mg/kg) or WE (500 mg/kg for Au and 250 mg/kg for Th and Ap) 30 min before glucose loading (glucose: 1 g/kg). The WE of Au, Ap and Th produced a significant decrease in glycemia after glucose loading. In the IVGTT the WE of Ap and Th produced a significant decrease in glycemia 60 min after i.v. glucose loading (0.5 g/kg). The addition of the WE of Au (500 mg/kg), Ap or Th (250 mg/kg) induced a significant inhibition of jejunal glucose absorption, (31.6%, 28.5% and 40.5% respectively). This effect could explain in part the significant antihyperglycemic effect observed in the OGTT model but it does not exclude other effects on glucose homeostasis, particularly for Ap and Th. Toxicity tests (high LD50 value) suggest no adverse effect of the use of these plants. PMID- 17867562 TI - Antibacterial and antiviral naphthazarins from Maharanga bicolor. AB - Maharanga bicolor, Boraginaceae, is used in the Nepalese ethnomedicine for the treatment of several diseases. In the course of screening investigations the dichloromethane extract of the roots of Maharanga bicolor was found to inhibit the growth of gram positive bacteria. Bio-assay directed fractionation led to the isolation of five active naphthazarins, deoxyalkannin (1), alkannin (2), acetylalkannin (3), alkannin beta-hydroxyisovalerate (4) and alkannin beta acetoxyisovalerate (5). Compounds 2-5 showed antibacterial activity against multi resistant human pathogenic Staphylococcus and Enterococcus species and 1, 4 and 5 showed antiviral activity against herpes simplex virus type-1. PMID- 17867563 TI - N-substituted tetrahydro-2,4-dioxoquinazolin-1-yl acetic acids as aldose reductase inhibitors. AB - Novel N-substituted tetrahydro-2,4-dioxoquinazolin-1-yl acetic acids characterized by formal replacement of the substituted benzyl moiety by cyclohexylmethyl and n-heptyl residues, respectively, were synthesized and evaluated as aldose reductase inhibitors. PMID- 17867564 TI - Effect of processing temperature on Eudragit RS PO microsphere characteristics in the solvent evaporation process. AB - Eudragit RS PO microspheres containing stavudine as a model drug were prepared by the solvent evaporation method using acetone liquid paraffin system. The influence of processing temperature: 10, 30 and 40 degrees C on various parameters like particle shape, size distribution, drug loading, drug polymer interaction and release kinetic were studied. It was found that at lower temperature (10 degrees C) small particles of irregular size, rough and wrinkled surface were formed, whereas higher temperature gradually increases the particle size as well as improves the shape and smoothness of microspheres. It was found that temperature had no effect on encapsulation efficiency and drug polymer compatibility. Drug release rate from microspheres were found to be a function of mean particle size distribution. PMID- 17867565 TI - Nursing care in life, death and disaster. ANA Atlanta conference. PMID- 17867567 TI - New clinical placement database holds promise to ease bottlenecks. PMID- 17867566 TI - Nurse staffing: challenges in measurement and planning. PMID- 17867568 TI - Characterizing microbial exposure with ergosterol, 3-hydroxy fatty acids, and viable microbes in house dust: determinants and association with childhood asthma. AB - The authors assessed determinants of ergosterol, 3-OH fatty acids (FAs), and viable microbes in vacuum cleaner dust, and investigated the association between these microbial markers and childhood asthma. The authors studied the homes of 36 children who were new cases of childhood asthma and the homes of 36 controls. Home characteristics explained 34% to 44% of the variation in levels of different microbial groups. Determinants of 3-OH FAs were a lower level of cleanliness, having a fireplace, having livestock, and moisture damage; determinants of viable bacteria were the level of home repair needed and the material used in the building frame of the home. Ergosterol was associated with the presence of livestock and the practice of cleaning rugs outside; viable fungi was associated with the material used in the building frame, visible mold, and the practice of cleaning rugs outside. Exposure to mesophilic actinomycetes was nonsignificantly associated with risk of asthma. The authors concluded that the variation of microbial levels in dust could be explained relatively well by home characteristics, and suggested that exposure to mesophilic actinomycetes may increase the risk of new asthma. PMID- 17867569 TI - Evaluation of bronchial hypersensitivity in veterans with sulfur mustard gas induced skin or eye manifestations without respiratory symptoms: 15 years after exposure. AB - The authors evaluated the prevalence of bronchial hypersensitivity in subjects who had confirmed exposure to sulfur mustard gas (SMG) but no overt respiratory manifestations. They chose 30 patients who had proven skin or eye manifestations secondary to SMG, and performed baseline and provocative pulmonary function testing with cold air and methacholine. The authors performed the same procedure on 30 control volunteers. After challenge testing with cold air and methacholine, bronchial hypersensitivity was detected in 7 (23.3%) and 9 (30%) of cases, respectively. Only 1 control subject showed hypersensitivity after provocation testing with cold air (p = approximately .05); the same control subject showed a positive challenge testing result with 10 mg/ml of methacholine (p < .02). The kappa coefficient for evaluating the effectiveness of the cold air, as a provocative agent for challenge testing, was 93.3%. PMID- 17867570 TI - Assessment of genotoxic damage in lymphocytes of hospital workers exposed to ionizing radiation in Argentina. AB - The authors aimed to assess genotoxic damage in the lymphocytes of workers chronically exposed to ionizing radiation. The studied population included 15 exposed donors of the radiology unit of a public hospital in La Plata, Argentina. The control group included 15 nonexposed employers from administrative areas that the authors matched by age, sex, and smoking habits. The mean frequency of cytogenetic damage was higher in the exposed group than in the unexposed group for aneuploidy and structural chromosome aberrations. They observed the highest difference when achromatic lesions (or gaps) were considered. The comet assay showed that the frequency of cells with low damage was higher in the exposed group than in the unexposed group. A mean length analysis showed significant differences between exposed and nonexposed people. The results can be considered to be consistent evidence of occupational radiation exposure, and the results indicate that the workers must be advised to avoid or minimize their exposure. PMID- 17867571 TI - Reverse osmosis filter use and high arsenic levels in private well water. AB - Inorganic arsenic causes cancer, and millions of people worldwide are exposed to arsenic-contaminated water. Regulatory standards for arsenic levels in drinking water generally do not apply to private domestic wells. Reverse osmosis (RO) units commonly are used by well owners to reduce arsenic concentrations, but may not always be effective. In a survey of 102 homes in Nevada, 19 used RO devices. Pre- and post-RO filtration arsenic concentrations averaged 443 microg/l and 87 microg/l, respectively. The average absolute and percent reductions in arsenic concentrations after filtration were 356 microg/l and 79%, respectively. Postfiltration concentrations were higher than 10 microg/l in 10 homes and higher than 100 microg/l in 4 homes. These findings provide evidence that RO filters do not guarantee safe drinking water and, despite regulatory standards, some people continue to be exposed to very high arsenic concentrations. PMID- 17867572 TI - Peak expiratory flow rate variability is not affected by home combustion sources in a group of nonsmoking women. AB - Exposure to indoor combustion has been associated with health effects, especially in women, in many parts of the world. The authors studied 648 nonsmoking women in nonsmoking households who measured their peak expiratory flow rate for 2 weeks, during the winter, when ambient air pollution is lower. The participants recorded any use of secondary home heating combustion sources (eg, kerosene heaters, fireplaces, wood-burning stoves). Peak expiratory flows were expressed as the variability percent mean for the 2-week measurement period. Adjusting for educational level, ethnicity, and history of allergies, the 2-week variability in peak expiratory flow was associated with a previous physician diagnosis of asthma (OR = 2.88; 95% CI = 1.59-5.21) and black or Hispanic ethnicity (OR = 2.02; 95% CI = 1.27-3.22), but was not associated with use of any supplementary home combustion sources among either asthmatic or nonasthmatic women. PMID- 17867573 TI - Pleural plaques: a review of diagnostic issues and possible nonasbestos factors. AB - The authors reviewed nonasbestos etiologies and diagnostic issues related to pleural plaques. Through searches of PUBMED and DIALOG using the term pleural plaques, they identified 125 articles. The authors found additional references by reviewing citations of these 125 articles. Exposure to nonasbestos agents (eg, erionite, silicates, manmade fibers) was cited as a possible factor in plaque development, although this association was based on limited data; empyema, tuberculosis, rib fractures, and hemothorax also were cited as potential etiologies. Rib companion shadows, fat, intercostal vessels, and muscles can appear as plaques; thus, radiographic diagnosis requires careful evaluation. Chest x-rays show large false negative and varying false positive rates. The terms calcification and thickening often were used as synonymous with plaques; however, these terms have different meanings. The authors concluded that plaques may be associated with nonasbestos exposures and certain medical conditions. Without a thorough exposure/medical history, plaque reports can be misleading. PMID- 17867574 TI - [Omnis cellula e cellula--Pathology in Berlin 2006]. PMID- 17867575 TI - Types of colorectal adenoma. AB - While most colorectal polyps can be classified as either adenomas (AD) or hyperplastic polyps (HP), approximately 5 % have some of the features of these lesions but are distinguishable from both. These lesions include sessile serrated adenoma or polyp (SSP), mixed polyp (MP), and traditional serrated adenoma (SA). These relatively recently described entities account for only about 3%, 1% and 1% of colorectal polyps respectively. Nevertheless, they may serve as the precursor lesions of the subset of colorectal cancer (15-20%) with extensive DNA methylation, mutation of BRAF, and DNA microsatellite instability. This overview summarises the key morphological features of traditional and newer types of colorectal polyps. It also discusses the differing molecular signatures of polyps, focusing on mutation of BRAF and KRAS and alterations of TP53 and the DNA repair genes O-6-Methylguanine DNA Methyltransferase (MGMT) and MLH1. A more detailed description of the features of MPs and SA is then developed and it is shown that these polyps are highly heterogeneous lesions in terms of both morphology and molecular pathology. Finally, a simple working nomenclature for the diagnostic reporting of colorectal polyps is suggested. In this system, MPs and SAs are combined as 'serrated polyps with dysplasia'. It is likely that the recognition and diagnosis of serrated polyps of the colorectum will assume increasing importance in the coming years and that their complex morphology and molecular heterogeneity will present interesting challenges for pathologists, scientists and clinicians. PMID- 17867576 TI - [Diagnosis and clinical decision making: a conceptional framework for predictive pathology]. AB - In the clinical pathway of diagnosis and therapy of diseases two decisions are distinguished: diagnostic and therapeutic decision. The former is analysed by decision tables, the latter by decision trees. In both decisions pathology plays a dominant role, especially as a gold standard that is a test to which most people have developed trust. This definition is remarkably soft. An efficient diagnostic prediction depends on a high prevalence of the disease. This is frequently forgotten when tests have a high sensitivity and specificity. The mathematical concept behind this observation is the Bayesian theorem. This is highly important for predictive pathology because it allows to combine attributes with high likelihood ratio simply by multiplication and has been shown to be remarkably stable, e. g. in the differential diagnosis of acute abdominal pain. Pathology should take the leadership in prediction since it has a considerable power as the gold standard of many tests. However, a network is advisable with other basic disciplines. PMID- 17867577 TI - [Cytomics and receptor interaction]. AB - The system of erbB-receptor-tyrosine-kinases (RTKs) appears considerable complex because four erbB-receptors crossactivate each other via homo- and heterointeraction upon ligand binding. This complexicity is additionally elevated by scores of corresponding growth factors with unique binding- and activation specificity. The total receptor-ligand system provides the basis for intracellular signal- diversity and -specificity. Significant oncological importance is attributed to the family of erbB-RTKs, which are known to cause and contribute to carcinogenesis, tumor progression, invasion, metastasis, e. g. based on uncontrolled cell growth and cell proliferation. The detection of erbB receptor gene amplification or corresponding protein overexpression is well established in tumor diagnosis and an essential element for therapy decision. However, the assessment of the coexpression profile of erbB-receptors and the presence or absence of growth factors has not been implemented into pathological diagnosis so far. Cytomics represents a novel discipline in systems-biology. It is dedicated to understand and resolve biocomplexicity of cells, cellular components, and cell-systems. Understanding the function of the integrated erbB receptor-system on a cytomic level will facilitate to more precisely follow-up the course of disease and thereby to elevate prognosis to the level of individual prediction. A system biological approach should involve the analysis of molecular function and dynamics on a single cell level and thereby is expected to characterize the disease in terms of a given molecular equivalent. Additionally, new and highly specific drug targets are likely to be identified. The comprehensive analysis of the complex molecular erbB-receptor system will enable to stratify tumor patients more precisely and simultaneously to specify erbB receptor based therapeutic strategies in terms of individualized medicine. PMID- 17867578 TI - [DNA methylation: potential for diagnosis, prognosis and therapy--prediction in oncology]. AB - In the last decades, a great variety of novel therapeutic regimens have become available for cancer. These therapies often are very specific and thus effective only in subsets of cancer patients. This has led to an increased need for the clinician to specifically choose the therapeutic strategy the patient profits most from, but at the same time avoiding over-treatment. This situation has a profound impact on the methods in diagnostic tumor pathology, since it requires precise pre-therapeutic tumor characterization to support the clinical management of the individual case. A common and early event in cancer is aberrant DNA methylation within gene regulatory regions which affects a variety of genes with different functions. Altered DNA methylation has been shown to carry prognostic as well as predictive information. As a DNA-based marker that can be analyzed in routine formalin fixed tissue, DNA methylation offers a series of technical advantages which allow for introduction into a routine lab. Here we review well established DNA methylation markers and discuss their potential for clinical use. PMID- 17867579 TI - [Role of pathology: tumour banks, quality of tissue and more?]. AB - Human tissue, in particular tumour tissue, represents a basic requirement for the research topic "predictive pathology". For many approaches unfixed fresh frozen tissue is required. For the recruitment, asservation and storage standard operating procedures (e. g. "informed consent") have to be followed. The role of the pathologist in the organization of tumour banks is manifold. 1. The collection of fresh frozen tumour tissue has to be performed without interference with the diagnostic procedure, optimally by a trained pathologist within the operating theatre. 2. Prior to the use of fresh frozen tissue for non morphological prodecures a histopathological documentation of tissue has to be performed. 3. In many cases complementary analysis of paraffine embedded tumour tissue for the same cases is necessary (e. g. immunohistochemistry, tissue microarray analyses, etc.). 4. For special questions (laser)microdissection of tissue has to be applied and also requires pathohistological knowledge. 5. Interpretation of results of non morphological analysis has to be correlated with pathohistological findings. Furthermore, in addition to the above mentioned research goals, tumour banks are an important source for future diagnostic procedures in particular for individualiziation of tumour therapy which will be developed in the future. As a conclusion, the pathologist plays a pivotal role in the organization of tumour- respectively tissue banks. Care must be taken that banks should be organized on an interdisciplinary basis since besides tumour tissue clinical data are required for most scientific studies. PMID- 17867580 TI - [Predictive pathology: concept and dimensions of clinical trials]. AB - Most new treatment principles are based on pathophysiological knowledge. They are, however, only effective in subgroups of patients where the pathophysiological concepts apply. The definition of the respective patient groups using clinical and laboratory findings is rather unsuccessful. Pharmakogenetic approaches have as well been disappointing. Since outcomes are often multifactorial single polymorphisms have not been sufficient. Predictive pathology will need to use gene signatures or functionally defined genetic markers in order to solve the problems. PMID- 17867581 TI - [Soft tissue sarcomas: the role of histology and molecular pathology for differential diagnosis]. AB - Soft tissue sarcomas include a wide spectrum of different entities. The so-called small round blue cell tumors and spindle cell tumors are difficult to classify based solely on conventional histology. To identify different subtypes of tumors special histochemical and immunohistochemical techniques are necessary. Analysis of protein expression by immunohistochemistry provides a helpful tool to investigate the histogenesis of tumors. A basic spectrum of antibodies should be included to study these tumors: Desmin and myogenin (or MyoD1) for skeletal differentiation; S-100, NSE, CD56, and synaptophysin for neural/neuroendocrine differentiation; CD3, CD20, and CD79 alpha for malignant lymphomas; CD34, sm actin, and beta-catenin for spindle cell tumors; additional antigens, e. g. Ki-67 and p 53, for estimation of proliferation and tumor suppressor gene malfunctions. Nevertheless, the molecular analysis of soft tissue sarcomas is necessary for demonstration of specific translocations or gene defects to specify and proof a diagnosis. For this purpose, RT-PCR for RNA expression analysis of gene fusion transcripts and multi-color FISH for analysis of chromosomal rearrangements are used. Further investigations, using DNA microrrays may help to subclassify such tumors, with respect to prognosis or prediction of therapeutic response. PMID- 17867582 TI - [Therapeutic targets in gastrointestinal stromal tumors]. AB - Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors in the gastrointestinal tract, metastasize in up to 50 % of cases and are resistant to conventional radio- and chemotherapy. They are characterized by the expression of the type III receptor tyrosine kinase KIT which is the most important diagnostic immunohistochemical feature. Genomically, the majority of GISTs carry heterozygous mutations in the KIT or the PDGF receptor alpha gene leading to an autophosphorylation of the respective receptor protein. The evaluation of the mutational status allows the subdivision of GISTs into different prognostic sub groups. For example, GISTs carrying an activating mutation in PDGF receptor alpha are most often located in the stomach and seem to have a better prognosis than GISTs with a KIT mutation. Specific mutational subtypes of KIT mutations in exon 11 (esp. proximal deletions of codons tryptophane-557 and lysine-558) have a significantly higher metastatic risk than GISTs with KIT mutations located in the distal part of exon 11 (esp. insertions/duplications). GISTs in the small bowel most often carry KIT exon 9 mutations and have a worse prognosis than GISTs with exon 11 mutations. Mutational subtype in KIT or PDGF receptor alpha not only influences the biological behavior of GISTs but also their response to treatment with imatinib, a tyrosine kinase inhibitor also inhibiting ARG, PDGF receptor beta and BCR-ABL. KIT exon 11 mutated tumors show response rates of up to 80 % of cases whereas KIT exon 9 mutated GISTs respond in less then 50 %. GISTs without detectable KIT mutation in these both exons often are resistant to imatinib. The development of secondary resistance to imatinib in GIST patients occurs in up to 40% of cases and is partly due to secondary KIT mutations occuring additionally to the primary mutation. Actually, several studies evaluate the efficacy of alternative small molecules such as SU 11248, RAD001 and AMG706 inhibiting signal transduction pathways downstream of KIT and PDGF receptor alpha. In summary, mutational status in KIT or PDGF receptor alpha of GISTs is relevant for prognosis, for response to treatment and for further insights into mechanisms of treatment failure. PMID- 17867583 TI - [Goals of therapy]. AB - Relevant criteria to assess specific diseases have been heavily discussed since Rudolf Virchow when morphologic changes represented the center of interest. However, nowadays presence and severity of disease cannot exclusively depend on the mere absence or presence of morphologic criteria anymore. The progress in basic and clinical science, moral values and economic constraints imply to reflect, concretize and ultimately operationalize the goals of medical therapy. Recent advances in molecular biology and genetics have lead to further understanding of pathophysiological mechanisms of disease and opened new ways for sophisticated and individualized therapeutical approaches. It is important to reconsider the definition of health and appropriately address functional and quality of life aspects. The categorical classification of therapeutical options, i.e. curative versus palliative therapy, does not provide satisfying answers to several clinical scenarios such as early stage prostate cancer in older adults or functional limitations in patients with peripheral arterial disease. Clinical research does acknowledge increasingly that relevant outcomes extend well beyond the quantitative prolongation of life. The scientific field of health services research is supposed to increase the evidence base of these decisions. Lastly, the goals of therapy should not be defined by physicians alone. It is important to inform the patient appropriately and discuss individual prognosis, therapeutical options and goals. Ultimately, therapy should be based on a shared decision making process. PMID- 17867584 TI - [Hepatocellular carcinoma: novel molecular aspects for differential diagnosis and therapy]. AB - Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide and shows increasing incidence. Multimodal strategies against HCC include primary (e.g. immunisation) and secondary (e. g. antiviral therapy) prevention, surgical approaches, novel specific systemic therapies (targeted therapy), and the treatment of comorbidity (cirrhosis). New molecular approaches are currently under development and tackle several specific targets. In this context pathology is needed in many aspects: experimental strategies, development of valid tumor-relevant diagnostic tests as well as morphological evaluation in the context of clinical studies and finally in routine diagnosis. PMID- 17867585 TI - [Herceptin therapy in breast cancer: new indication?]. AB - HER-2 belongs to a family of four transmembrane receptor tyrosine kinases that mediate growth, differentiation and survival of cells. HER-2 overexpression and amplification occurs in approximately 15 to 25 % of breast cancers and is associated with aggressive tumour behaviour. Herceptin (trastuzumab), a humanized monoclonal antibody directed against the extracellular domain of the HER-2 receptor, has been shown to have clinical activity in HER-2-positive advanced breast cancer when administered alone or in combination with chemotherapy. It has been approved for HER-2-positive metastatic breast cancer by the United States Food and Drug Administration in 1998 and in the countries of the European Union in 2000. Recently, promising results of the four randomized international multicenter trials evaluating the therapeutic benefit of Herceptin in the adjuvant treatment of HER-2-positive primary breast cancer have been reported. Data of the first planned interim analysis of the studies showed significantly improved disease-free survival in patients assigned to one year of Herceptin compared to the control groups even after short term follow up. These results caused an immediate wave of demand for Herceptin in adjuvant therapy. Results of these studies are critically reviewed. Furthermore, the available preliminary results from studies using Herceptin in the primary (neoadjuvant) therapy of HER 2-positive breast cancer are addressed and possible implications for HER-2 testing are discussed. PMID- 17867586 TI - [Her-2/neu analysis--new data?]. AB - Her-2 status determination is an essential prerequisite before considering patient eligibility for treatment with trastuzumab. Currently the most common techniques to assess Her-2 status in routine practice are immunohistochemistry (IHC) and dual color FISH for receptor expression and gene amplification analysis, respectively. Despite both methods are well-established in breast cancer there are a variety of yet unsolved questions: 1. Do we really need IHC since interlab variation is still quite high (up to 30%)? 2. Are FISH and CISH equivalent techniques? 3. Are there any precautions to be taken if Her-2 is tested in non-breast cancer samples? 4. What is the value of Her-2 status in blood serum (ELISA)? 5. Do we get better response prediction if new Her2 antibodies, other techniques such as quantitative (q) RT-PCR or multiparameter assays according to downstream signalling pathways are applied? 6. Is Her-2 status still predictive when other therapeutic antibodies than trastuzumab (e. g. pertuzumab) or kinase inhibitors (e. g. lapatinib) are used? These questions will be discussed under the review of the recent literature and under own experiences obtained either by centralized Her-2 assessment in a variety of breast and non breast cancer therapy studies and within international ring studies between reference labs from Australia (M. Bilous), Canada (W. Hanna), France (F. Penault Llorcoa), Great Britain (M. Dowsett), Japan (R. Y. Osamura), and Netherlands (M. v. d. Vijver) in which we participated. PMID- 17867587 TI - [Preoperative chemotherapy in breast cancer and the development of new predictive markers]. AB - Neoadjuvant chemotherapy provides today a valid option for many patients with primary breast cancer. For evaluation of treatment response as well as for biomarker studies for prediction of response, an efficient collaboration between pathologists and gynaecological oncologists is essential. This report reflects aims and indication according to the current opinion, describes advantages and disadvantages in comparison to the conventional adjuvant approach and provides guidelines on how to conduct the whole treatment concept of neoadjuvant therapy. Current and projected study concepts of preoperative and following postsurgical treatments in Germany are introduced. While the basic principles of histopathological evaluation of tumour specimens from neo-adjuvant breast cancer studies are similar to conventional surgical therapy, some aspects of histopathological management are of special importance in these studies. PMID- 17867588 TI - [Breast cancer--known receptors, new pathways?]. AB - The deregulation of receptor tyrosine kinases is an essentiell factor in die initiation and progression of malignant tumours. With the introduction of Herceptin in the adjuvant therapy of invasive breast cancer, the determination of the c-erbB2 expression status became an essential part in the workup of breast cancer biopsies. The commonly used diagnostic algorithm is based on a detailed knowledge about molecular mechanisms and downstream signal cascades. In contrast to c-erbB2, the underlying molecular mechanisms and potential predictive parameters, associated with the expression of the Epidermal Growth Factor Receptor (EGFR) are likewise unclear. With the introduction of anti-EGFR directed therapies in the treatment of malignant tumours, an improved knowledge about the role in the progression of breast cancers is urgently needed. This article will focus on important improvements in the knowledge of EGFR-overexpression in breast cancer cells, especially in the context of egfr-amplifications. PMID- 17867589 TI - [Role of predictive pathology in oncology--example of new therapies targeting EGFR]. AB - New cancer-specific therapies are based on specific molecular alterations of malignant tumors which are targeted by small inhibitory molecules or specific antibodies. During the development of these agents potential molecular targets are characterized for their expression and importance for pathogenesis and clinical course of the disease. Frequently the assumption is made that the degree of expression of the target protein or the molecular alteration of the target gene allows a prediction if a certain patient will profit from the therapy against this specific protein or not. The first example was that breast cancer patients with overexpression and/or amplification of Her-2 respond to a Her-2 specific antibody (Herceptin) therapy. The expression or activation of the Epidermal Growth Factor Receptor (EGFR, Her-1) are altered in many epithelial tumours and clinical studies indicate that they have important roles in tumor aetiology and progression. Several EGFR-specific monoclonal antibodies and specific tyrosine kinase inhibitors were developed in the last years. Cetuximab is approved for the treatment of metastatic colorectal cancer and advanced squamous cell carcinoma of the head and neck and is investigated in numerous trials for other tumors. The expression of EGFR in the tumor was a prerequisite for the therapy in the first trials, giving the pathologist a central role in treatment decision. However, recent data clearly demonstrate that the degree of EGFR expression does not correlate with therapy response. Therefore a therapy should be not denied to a individual patient solely because of lack of EGFR expression in the tumor. Tyrosine kinase inhibitors (e. g. Gefitinib, Erlotinib) are effective in the treatment of non small cell lung cancer and also investigated in ongoing trials in many cancer types. The correlation of therapy response with both specific molecular alterations (EGFR tyrosine kinase domain mutations) and clinicopathological features (Asian ethnicity, women, non-smokers, bronchioloalveolar differentation) is a good example of the potential role of predictive molecular pathology in the future. PMID- 17867590 TI - [Global gene expression analysis and novel signalling pathways in Hodgkin lymphoma]. AB - To identify pathogenetic mechanisms in Hodgkin lymphoma (HL) we performed global gene expression profiling of four HL derived cell lines and compared the expression profiles with those of normal B cells and B cell non-HL. This analysis revealed a global loss of B-cell specific gene expression in Hodgkin Reed/Sternberg (HRS) cells (21). Further analysis showed that ABF-1 and Id2, which are both negative regulators of the B cell master transcription factor E2A and likely also Pax-5, are aberrantly expressed in HRS cell lines (11, 17). For Id2, immunohistochemistry showed expression in the HRS cells of all cases, and E2A could be coimmunoprecipitated with Id2 from HRS cell lines, indicating that the aberrant Id2 expression may indeed contribute to the loss of the B-cell specific gene expression in HL (17). An analysis of the global gene expression data for aberrant expression of genes which are frequently involved in neoplastic transformation identified six receptor tyrosine kinases (RTK) aberrantly expressed in HRS cell lines. All RTKs were also (co)-expressed in primary cases and mostly activated by auto- or paracrine mechanisms (18). Analysis of greater number of cases identified a subgroup of HL which encompasses about 20 % of cases characterised by coexpression of at least four of the RTKs. An survey of several B cell lymphoma types with a pan-phospho-tyrosine specific antibody indicated that mediastinal large B-cell lymphoma is beside HL the only entity where aberrant TK activities cause an aberrantly high cellular phospho-tyrosine content in a significant fraction of cases. PMID- 17867591 TI - [Use and problems of the TNM classification]. AB - The TNM system is the most important classification for describing the anatomical extent of tumors. The residual tumor classification describes the completeness of tumor removal. Although the definitions of both systems seem clear and precise, the daily work offers questions on how to use special situations. Despite the importance of the TNM- and residual tumor classification in planning clinical management before and after treatment, the misinterpretations and inconsistencies in application diminish or abrogate their clinical utility. Some of the questions and problems will be addressed in this contribution. PMID- 17867592 TI - [Correlation of FGFR3 mutations and chromosomal alterations in bladder cancer]. AB - It has been suggested that mutation of FGFR3 is associated with non-invasive tumors of low malignant potential and low risk of recurrence and progression. The aim of this study was to analyze the distribution of FGFR3 mutations in bladder tumors of different grade and stage and to determine the relation of FGFR3 mutations to chromosomal alterations detected by CGH. Frozen sections of 100 bladder cancer samples served as templates for manual microdissection. DNA was isolated from dissected samples containing at least 80% tumor cells. Mutations in FGFR3 were analyzed by SNaPshot analysis. CGH was carried out according to standard protocols. FGFR3 mutations were detected in 45 out of 92 samples (48.9 %). Concerning T-category, the following mutation frequencies occurred: pTa - 69 %, pT1 - 38 %, pT2/3 - 0 %. The mutation frequency was significantly associated with tumor grade: G1 - 72%, G2 - 56%, G3 - 4%. In pTaG1 tumors, mutations were found in 74 %. A significant lower number of genetic alterations per tumor detected by CGH was associated with FGFR3 mutations (2 vs. 8). This association was also seen in pTaG1 tumors: 2.5 (with mutation) vs. 7.5 (without mutation). Our results confirm that FGFR3 mutations characterize non-invasive low-risk tumors of low malignancy. The low malignant potential of these tumors is underlined by a low number of chromosomal alterations per tumor. Therefore, FGFR3 could represent a prognostic marker of chromosomally stable tumors with low malignant potential. PMID- 17867593 TI - [Parenchymal regression in chronic pancreatitis spares islets reprogrammed for expression of NFkappaB and IAPs]. AB - In chronic pancreatitis (CP), fibrous replacement of exocrine tissue spares islets. There is local production of IFNgamma and death ligands by inflammatory cells as well as TGFbeta and TRAIL by pancreatic stellate cells (PSCs), along with functional death receptor neo-expression and apoptosis in exocrine but not in endocrine cells. Moreover, islets are strongly induced for TRAIL-receptor(R)-4 lacking a functional death domain. TRAIL-R4 signalling in T-cells induces NFkappaB transcription factors which activate anti-apoptotic programs. Whether TRAIL elicits this response in endocrine cells, we tested human insulinoma cell line CM and determined NFkappaB subunits transcripts and NFkappaB dependent inhibitor of apoptosis proteins (IAPs) in normal pancreas (NP) and CP. We treated CM with cytokines, determined TRAIL-R expression by flow cytometry, graded degree of fibrosis in CP specimens, microdissected epithelial compartments, performed real time PCRs for NFkappaB subunits transcripts, and immunohistochemistry for IKK-gamma, IkappaB-alpha, RelA, survivin, and cIAP1. In CM, TGFbeta/IFNgamma/TRAIL induced TRAIL-R4 surface expression. TRAIL/ IFNgamma, upregulated NFkappaB subunits and survivin while down-modulating 1kappaBalpha. NP epithelia had low RNA levels of NFkappaB subunits. These were increased in parenchymal areas of CP with severe fibrosis and most intensely in islets. The NFkappaB regulated proteins IkappaBalpha, survivin, and cIAP1 were found in corresponding sites, again, at highest levels in islets surrounded by fibrosis. In CP, islets not only evade immune attack by non-exposure of functional death receptors in presence of TRAIL-R4. They also neo-express NFkappaB subunits, survivin, and cIAP1. This apoptosis-inhibitory security program might be enforced by PSC-derived TRAIL. PMID- 17867594 TI - [Salivary duct carcinomas comprise phenotypically and genotypically diverse high grade neoplasms]. AB - Salivary duct carcinomas (SDC) are high grade neoplasms morphologically reminiscent of breast ductal carcinomas. Whereas the latter are well characterized, the body of immunophenotypic and cytogenetic data on SDC is limited. We studied 23 SDC by conventional histology, immunohistology, in situ hybridization, and comparative genomic hybridization (CGH). Data were subjected to biomathematical analysis in comparison to previously characterized breast ductal carcinomas in situ and invasive ductal carcinoma cases. Most SDC stained for cytokeratins (Ck) Ck 8/18 (77 %) or Ck 5/6 (30 %), 30 % of cases expressed the androgen receptor (AR), 14 cases (63 %) expressed c-erbB2, and one case stained for prostate specific antigen. Except for two cases, Ck 8/18 and Ck 5/6 were not coexpressed. Ck 8/18 expression positively correlated with presence of c erbB2 and AR. At variance, Ck 5/6 correlated positively with p63 and inversely with both AR and c-erbB2 expression. Ck 5/6 and p 63 co-expression was also found in a distinct population of ductal epithelial cells of normal salivary glands. CGH analysis of SDC revealed increasing numbers of alterations in correlation with advanced diseases, but no recurrent alterations. Cluster analysis of phenotypic and genotypic markers assigned both salivary and breast carcinomas to numerous clusters independent of the primary tumour site. Although undistinguishable by conventional histology, SDC are heterogeneous, comprising at least two immunophenotypically distinct subgroups of neoplasms. Cluster analysis suggests several distinct patterns of gene expression common to both primary sites explaining morphologic parallels between SDC and high grade breast cancer. PMID- 17867595 TI - C-kit expression in high-risk breast cancer subgroup treated with high-dose or conventional dose-dense chemotherapy. AB - The proto-oncogene c-kit is known to be expressed in poorly differentiated breast cancer. In this study, we retrospectively evaluated the prognostic and predictive impact of c-kit in a high risk subgroup of breast cancer patients (>9 axillary node metastases) who received high-dose (HDCT) or dose-dense (DDCT) conventional chemotherapy and correlated these findings with the expression of the basal-type markers CK5 and CK 17, estrogen (ER) and progesterone (PR) receptor, Her-2/neu and MIB 1. C-kit, CK5, CK17, ER, PR, Her-2/neu and MIBI expression was evaluated immunohistochemically using tissue microarrays containing breast cancer samples from 236 patients who were randomized to the WSG AM01 trial (median follow-up of 60 months). There was a significant overall survival (OS) benefit for patients receiving HDCT compared to DDCT (p = 0.027). C-KIT expression was found in 12 % of all breast cancers and correlated with a poorer OS in multivariate analysis (p = 0.051). Furthermore, c-kit correlated with high grade (p = 0.019), CK5- and CK17-positivity (p <0.0001 and p = 0.001, respectively) and ER- and PR-negativity (p = 0.04 and p = 0.008, respectively). In contrast to CK5 and CK17, patients with c-kit positive breast cancers revealed no benefit from high-dose chemotherapy. These findings underline that c-kit expression represents an independent negative prognostic marker in high-risk breast cancer. Correlation with CK5 +/CK17+ and ER-/PR-suggests that c-kit positive carcinomas are at least partly of basal-type. PMID- 17867596 TI - [Receptors for luteinizing hormone releasing hormone expressed on melanoma, renal cell carcinoma and non Hodgkin lymphoma can be used for targeted chemotherapy with cytotoxic luteinizing hormone releasing hormone analogues]. AB - AIMS: Cytotoxic luteinizing hormone releasing hormone (LHRH) analogues AN-152 and AN-207 consist of [D-Lys6] LHRH linked to doxorubicin or its hyperactive derivate AN-201 and bind with high affinity to LHRH receptors. We evaluated the use of AN 207 and AN-201 in a nude mice model. In order to provide a rationale for the possible use of cytotoxic LHRH analogues in different malignancies we investigated the expression of LHRH-R in human renal cell carcinoma (RCC), melanoma and non Hodgkin's Lymphoma (NHL). METHODS: The expression of LHRH-R was examined in surgically removed human specimens of primary tumours and metastases from 37 RCC, 19 melanomas and 17 NHLs. In addition, human tumour cell lines expressing LHRH receptors were transplanted into nude mice and anti-tumour efficacy and systemic toxicity of AN-207 and its cytotoxic radical AN-201 were compared in various experiments. RESULTS: Positive staining for LHRH receptors was found in all of the RCC (37/37) and the melanoma specimens (19/19) as well as in 100% (10/10) of the NHLs. In in vivo experiments AN-207 significantly inhibited tumour growth while the cytotoxic radical alone was ineffective. Furthermore, side effects were reduced with targeted therapy. CONCLUSIONS: LHRH receptor expression was found to be very high in melanomas, RCCs and NHLs. Therefore targeted therapy with cytotoxic LHRH analogues may be a promising, novel therapy for advanced stages of these tumours. A first clinical trial with AN-152 was initiated recently in breast cancer patients. PMID- 17867597 TI - [Cell-specific deletion of glucosylceramide synthase in brain leads to severe neural defects after birth]. AB - AIMS: Gangliosides, i. e. sialic acid containing glycosphingolipids, constitute a major component of neuronal cells and are thought to be essential for brain function. UDP-glucose: ceramide glucosyl-transferase (Ugcg) catalyzes the initial step of glycosphingolipid (GSL) biosynthesis. A total deletion of the Ugcg-gene in mice led to embryonic lethality. In order to gain insight into the role of gangliosides in brain development and function, a cell specific disruption of Ugcg was performed. METHODS: A cell specific disruption of Ugcg in mice was performed using the Cre/loxP-system. LoxP-flanked Ugcg-mice were generated and crossed with nestin-cre mice. RESULTS: The nestin-promoted gene deletion in neuronal cells was indicated by the absence of virtually all gangliosides already at stage E15.5. Shortly after birth mice showed dysfunction of cerebellum and peripheral nerves, associated with structural defects. Axon-branching of Purkinje cells was significantly reduced. In primary cultures of neurons dendritic complexity was clearly diminished, while pruning occurred. Myelin sheaths of peripheral nerves were broadened and focally severely disorganized. GSL deficiency also led to a downregulation of gene expression sets involved in brain development and homeostasis. Mice died approximately 3 weeks after birth. CONCLUSIONS: The pronounced neurologic symptoms in postnatal mice with neuronal specific deficiency of glucosylceramide synthesis demonstrate that GlcCer-derived GSL may not serve functions essential for early brain development. They are, however, required for neuron differentiation and brain maturation. PMID- 17867598 TI - [Effective data collection in cancer research: an all-in-one database solution]. AB - Tissue banks containing human malignant and benign tissue have become highly important for modem cancer research. They provide an excellent source of information with respect to pathological states and processes. Nowadays tissue samples can be examined using a broad variety of molecular biology methods, at the levels of DNA, RNA and protein. However, these new possibilities impose great expectations from the user side towards tissue banks and their associated databases. Nowadays a database that only manages tissue samples is not timely anymore. In fact a modern database should be capable of registering arbitraty amounts of tissue relevant information in an easily searchable way. In order to simplify the often complicated and time consuming process of data collection, we have developed a software solution that centralizes various aspects of tumor tissue banking. The main task of this software is not only to administer tissue samples but also to provide a centralized data platform for scientists which support their research. To achieve our goals we have constructed a tissue database which is supported by an Oracle System. The access to this database has been made possible with a light-weight, self-developed Java Client Program. The system possesses high levels of security and the access to information in the database is strictly controlled by preset permissions. A flexible search mechanism is also readily available for speedy data extraction according to various criteria. This solution provides us with an "All-in-one" tool for the purpose of flexible and efficient data collection and management in cancer research. PMID- 17867599 TI - [Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho-STAT5 accumulation]. AB - AIMS: Suppressors of cytokine signaling (SOCS) negatively regulate Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling involved in proliferation, survival, and apoptosis. We previously showed a loss of SOCS-1 function due to deleterious mutations in a major subset of mediastinal B-cell lymphoma (MBL). In MBL cell lines this leads to retarded JAK2 degradation and sustained phospho-STAT5 action results in enhanced DNA binding of phospho STAT5. METHODS: To investigate the SOCS-1 gene we laser-microdissected Hodgkin and Reed-Sternberg (HRS) cells of 19 classical Hodgkin lymphoma (cHL) and performed sequencing analysis. To assess phospho-STAT5 status immunohistochemistry on the corresponding paraffin-embedded cHL tumor tissue was done. RESULTS: We detected mutations of the SOCS-1 gene in HRS cells of 8 of 19 cHL samples and in 3 of 5 cHL-derived cell lines. Moreover, we found a significant association between mutated SOCS-1 of isolated HRS cells and nuclear phospho-STAT5 accumulation in HRS cells (P <0.01). CONCLUSIONS: In conclusion, these findings support the concept that MBL and cHL share overlapping features and that defective tumor suppressor gene SOCS-1 triggers an oncogenic pathway operative in both lymphomas. PMID- 17867600 TI - [Aberrant promoter methylation as biomarker for molecular cytological diagnosis of lung cancer]. AB - Aberrant promoter methylation represents a main mechanism of tumor suppressor gene inactivation and may serve as a new source for biomarker discovery. This study investigated its applicability as a molecular tool for lung cancer diagnostics on bronchial aspirates. A methylation assay was developed applying a quantitative methylation specific real-time PCR (QMSP). A total of 552 patients with the differential diagnosis of lung cancer were investigated. The QMSP findings on bronchial aspirates were compared with the methylation status of respective genes investigated in microdissected tumor tissues (QMSP, cloning and sequencing of promoter regions after bisulfite conversion). Among the genes tested a marker panel consisting of APC, p16(INK4a) and RASSF1A proved to be the best suited for lung cancer diagnostics. This panel allowed for a correct diagnosis of lung cancer in cases with an ambiguous or false negative conventional cytology. In a cohort study on 247 patients, the combination of histology (sensitivity 59 %), cytology (sensitivity 44 %) and QMSP-assay (sensitivity 53 %) raised the sensitivity of a single bronchoscopy for the diagnosis of lung cancer up to 81%. The methylation assay yielded its major diagnostic surplus with respect to peripheral tumors representing 59 % of all primaries detected. In patients without antecedent lung cancer its specificity considering malignancy was >99 %. Therefore, the QMSP-assay is a promising technique which could enhance the sensitivity and diagnostic impact of conventional cytology. The assay is applicable to residual material of regular diagnostic cytology even in retrospect. PMID- 17867601 TI - [Molecular pathological analysis of neoplastic mast cells with regard to the actual WHO classification of mast cell neoplasias]. AB - Detection of activating c-kit mutation D816 V is one of five criteria for the diagnosis of systemic mastocytosis (SM). The aims of this study were to (I) establish molecular methods for the detection of these mutations in paraffin embedded biopsies, (II) determine the frequency of these mutations in mastocytoses and control tissues, (III) determine the frequency of these mutations in laser-microdissected lesional and nonlesional mast cells (MC), and (IV) investigate these matutions as a marker for clonality in cases with SM and associated clonal hematologic non-mast cell lineage diseases (SM-AHNMD). Formalin fixed and paraffin-embedded biopsies of 48 patients with cutaneous mastocytosis (CM), 55 cases with various forms of SM, and 239 controls were investigated by PNA-mediated PCR-clamping. In addition, nested PCR amplified DNA of pooled microdissected single mast cells (MC) was investigated by melting point analysis. Activating c-kit mutation codon 816 mutations were detected in 38 % (18/48) of CM, in 91% (50/55) of SM, in 5 % (2/39) of MC hyperplasia and in none of 200 hematologic non-MC neoplasias. c-kit mutations were detected significantly more frequent in lesional MC as compared to non-lesional MC (p = 0,003). In 6/15 (40 %) cases with SM-AHNMD the same c-kit mutations were detected in microdissected MC and AHNMD cells. This study underlines the concept of the actual WHO classification of mastocytoses. By establishing methods for the detection of c kit codon 816 mutations in paraffin-embedded tissues, the pathologist holds a central position in the diagnosis of systemic mastocytoses. PMID- 17867602 TI - [A new quantitative DNA-methylation analysis of MSI colorectal cancers helps to separate sporadic colorectal cancers from HNPCC-candidates]. AB - AIMS: Promoter hypermethylation is a common mechanism for epigenetic control of gene expression and occurs frequently in tumors silencing tumor suppressor genes. Our aim was to establish a quantitative and precise method to analyze promoter methylation of tumor samples in order to identify HNPCC candidates. METHODS: We established a new methylation specific relative quantitative real-time PCR technique for analysis of the methylation status of the hMLHI promoter in colorectal cancers (CRC). We determined methylation status of both the distal and proximal hMLH1-promoter region. The methylation quantification (MQ) was performed with cell line DNA and archival paraffinized tissue sections. RESULTS: The accuracy of our analysis was validated with spiking experiments of methylated and unmethylated DNA. We assessed the hMLH1 methylation status 56 CRC patients with known microsatellite status and hMLH1 IHC. The methylation analysis divided the MSI-H CRC into two groups: Methylation positive sporadic CRC patients with a median age of 78.5 years and frequent BRAF mutations (82 %, p < 0.0001) and the unmethylated cancers from HNPCC candidates with a median age of 48 years. All hMLH1 positive sporadic MSS CRC were methylation negative. In all samples, the degree of methylation was mirrored by the shift of the melting points to higher temperatures. CONCLUSIONS: In summary we introduced a quantitative and qualitative technique to analyze DNA methylation that can be performed with any dense CpG island. Our methylation analysis provides a potent diagnostic tool to differentiate between sporadic MSI-H cancers showing MLH1 methylation and MLH1 unmethylated HNPCC candidates. PMID- 17867603 TI - [Mutation of the FGFR3 oncogene is an independent and favorable prognostic factor for tumor-specific survival in patients with urothelial carcinoma of the upper urinary tract]. AB - AIMS: Urothelial tumors of the upper urinary tract (UUTT) frequently display microsatellite Instability (MSI) and a distinct pathway of tumorigenesis resembling MMR-deficient colorectal cancers has been recognized for MSI-UUTT. For MSS-UUTT however oncogenic mechanisms as in bladder cancer (BC) are debated. Mutation of the oncogene FGFR3 has been linked to lower stage, lower grade and favourable clinical outcome in BC. The aim of this study was to evaluate FGFR3 mutation in MSI and MSS-UUTT. METHODS: 172 unselected UUTT were screened for MSI using the National Cancer Institute Consensus Panel and additional markers; FGFR3 status was studied using mutation analysis. Histopathological and clinical data were reviewed. RESULTS: Microsatellite status had no impact on histopathological or clinical outcome. 52/99 MSS, 10/22 MSI-low and 25/51 MSI-high UUTT displayed mut. FGFR3 respectively. Overall FGFR3 mutation was associated with favourable stage and grade (p <0.0001 and p <0.002), as 62.1% of mut. vs. 23.5 % of wt. FGFR3 UUTT were stage Ta and T1 and graded G3 in 25.3 % vs. 47.1% respectively. That effect depended on MS-status however, as FGFR3 mutation was related to lower stage (pTa and pT1) in MSS/MSI-L (mut 62.9 % vs. wt 18.7%; p <0.01) only as opposed to MSI-H (mut 60% vs. wt. 50%; p = 0,1) UUTTs and as FGFR3 mut UUTTs tended to display lower grade (G1 and G2) provided stable (mut 74,2 % vs. wt. 44.1%; p <0,01) as opposed to instable microsatellite status (mut 76 % vs. wt. 73 %; p = 0.7). There was no marked relation of MS-status or FGFR3 mutation to sex, age or tobacco-exposure; localization in the renal pelvis (p < 0.01) however was more prevalent in the FGFR3 mut group. As opposed to MSI-status FGFR3 mutation had a favourable impact on survival, as 24.1% vs. 54.2 % cancer related deaths occured in the mutated group (p <0.001); this effect was indendent on stage or MSI-status. Neither MSI- nor FGFR3-status had any influence on subsequent bladder tumors. CONCLUSIONS: FGFR3 mutation is frequent in UUTT and appears to be independent of MS-status; however it is related to significantly favourable histopathological parameters and clinical outcome in MSS cases. Thus our findings might back the notion, that MSS and MSI-UUTTs stem from different oncogenic pathways and that their differing molecular character might have some relevance. Further research is warranted to study the clinical behavior of these tumors and to evaluate a potential role for MS-status and FGFR3 as prognostic tools. PMID- 17867604 TI - [Urothelial neoplasms in individuals younger than 20 years show very few genetic alterations and have a favourable clinical outcome]. AB - AIMS: Urothelial neoplasms in patients 19 years or younger are rare, with conflicting data regarding clinical outcome and no molecular data available. METHODS: Urothelial tumors of 14 patients 4 to 19 years old were identified, reclassified according to the 2004 WHO classification and data on presentation, risk factors and outcome were collected. 14 cases were microdissected and extensive molecular analyses were done, including FGFR3 and TP 53 mutation screening, Comparative Genomic Hybridisation (CGH), Urovysion FISH analysis, PCR for HPV, microsatellite analysis using an extended NIH consensus panel for detection of microsatellite instability (MSI) and 6 LOH markers on chromosome arms 17p, 9p and 9q and immunohistochemistry for TP 53, MIB1, CK20 and the mismatch repair proteins hMSH2, hMLH1 and hMSH6. RESULTS: Based on the 2004 WHO classification, 1 urothelial papilloma, 7 PUNLMPs, 5 low grade, and 1 high grade papillary urothelial cancers were included. There were no multifocal tumors and only 1 patient had recurrence. All patients were alive with no evidence of disease (4.5 years follow-up). We did not find mutations in FGFR3, deletions of chromosome arms 9p, 9q or 17p, MSI or MRP loss or HPV positivity. Chromosomal alterations in CGH, urothelial dedifferentiation with CK20 over-expression or aneuploidy were rare and only detected in 3 cases. One TP53 mutation was found in the only tumor with overexpression of TP53. CONCLUSIONS: Urothelial neoplasms in individuals younger than 20 years have predominantly a low grade and favourable clinical outcome. The most frequent genetic alterations found in elderly patients are extremely rare. Urothelial neoplasms in young patients could represent a biologically distinct form of bladder disease with lack of genetic instability in most cases. PMID- 17867605 TI - [Rhabdomyosarcoma lysis by T cells expressing a human autoantibody based chimeric receptor targeting the fetal acetylcholine receptors]. AB - Rhabdomyosarcomas (RMSs) are the most frequent malignant soft tissue tumors of childhood. Since even aggressive multimodality treatments including autologous stem cell rescue have failed to improve the < 20 % overall survival rate of children with metastatic RMS, novel treatment approaches are urgently needed. Looking for potential targets for immunotherapies, we identified the gamma subunit of the fetal acetylcholine receptor (fAChR) as a specific and overexpressed membrane antigen in RMS. Additionally we established a duplex RT PCR with simultaneous amplification of alpha and gamma subunit message of the fAChR and the quantification of both transcripts resulting in alpha/gammaAChR ratio > 1 was 100% sensitive in alveolar and embryonal rhabdomyosarcoma. Since the fAChR was the first extracellular tumor marker that can distinguish rhabdomyosarcomas from nonrhabdomyomatous tumors and from normal muscle and therefore implies, that the fAChR may be a target for immunotherapeutic strategies, we synthesized a scFv antibody fragment directed against the fAChR and enigineered both a Pseudomonas exotoxin A based immunotoxin as well as a chimeric T cell receptor composed of the antigen-binding domain of the scFv fragment joined to the signaling domain of the T cell receptor zeta chain. The interaction of fAChzeta-transduced T cells with several RMS cell lines but not with fAChR-negative controls induced strong T cell activation, characterized by secretion of high amounts of interferon-gamma. Moreover after co-incubations with RMS cell lines fAChRzeta-transduced T cells as well fAChR specific immunotoxin induced specific receptor-concentration dependent tumor cell lysis. Therefore, fAChRzeta-transduced T cells and the fAChR specific immunotoxin respectively are promising new tools for the immunotherapy of rhabdomyosarcomas and may provide an effective complementary approach to eradicate residual or metastatic RMS cells in patients, since 1. RMS-direceted chemotherapies increase the expression of fAChR on residual RMS cells in vivo and 2. the fully human fAChR autoantibody fragment with low immunizing potential allows prolonged/permanent application of fAChRzeta transduced T cells/immunotoxin. PMID- 17867606 TI - [Fibroblasts of recipient origin contribute to broncholitis obliterans in human lung transplants]. AB - RATIONALE: The participation of circulating precursor cells in the development of experimental pulmonary fibrosing lesions in mice has been recently demonstrated. OBJECTIVES: This study analyzes whether circulating, bone marrow-derived fibroblastic precursor cells contribute to the development of fibrosing lesions in human lungs, especially bronchiolitis obliterans. METHODS: The occurrence of in situ-microchimerism in bronchiolitis obliterans lesions of human lung allografts (n = 12) as well as of autologous lung tissue from patients post bone marrow-transplantation (n = 2) was analyzed using laser-assisted microdissection after immunohistochemical labeling of leukocytes followed by STR-PCR-based genotyping. Combined immunofluorescence and fluorescence in situ hybridization for sex chromsomes was performed for independent confirmation in cases with appropriate sex mismatch (n = 2). MEASUREMENTS AND MAIN RESULTS: The bronchiolitis obliterans lesions of all twelve lung transplant patients contained considerable numbers of recipient-derived fibroblasts (mean: 32 %). The fibrosing pulmonary lesions of the two bone marrow-transplanted patients displayed also clear in situ-microchimerism. The in situ detection methodology confirmed these results, although to a lower degree (6-16%). CONCLUSIONS: These data clearly demonstrate the involvement of circulating fibroblastic precursor cells in the development of human fibrosing lung lesions and provide evidence that these cells are most probably bone marrow-derived. These results may open new venues regarding the prevention of fibrosis in lung transplants and potentially other organs. PMID- 17867607 TI - [Acute dyspnea of Mrs. D]. PMID- 17867608 TI - [Medullary osteoidosteoma of the os pisiforme]. AB - A case of a medullary osteoidosteoma of the pisiforme bone is presented that appeared as a light bulb on MR-Angiography while causing diffuse hypointensity of the pisiforme bone and of the surrounding soft tissue on T1- and diffuse hyperintensity of these regions on T2-w and T1- w postcontrast images. Although not surprising according to the typical appearance of osteoidostomas on triple phase scintigraphy, the light bulb sign of osteoidosteomas on MRA has not yet been reported and familiarity with this findings may be of value in order to avoid their confusion with vascular lesions such as aneurysms or pseudoaneurysms during MR-angiography. PMID- 17867609 TI - [Subacute weakness of the lower limbs]. AB - Complete and isolated herniation of the urinary bladder is extremely rare, and the consecutive appearance of bilateral urethral obstruction and renal failure is even rarer. We report about a 73 year old male presenting with massive nausea and muscular weakness. On physical examination he showed a giant inguinal hernia with involvement of the entire bladder along with evidence of bilateral hydronephrosis. His serum creatinine and potassium levels were markedly elevated most likely leading to his presenting symptoms of azotemia (nausea) and hyperkalemia (weakness). After transscrotal drainage and decompression of the bladder, a transurethral catheter was inserted. After gaining full renal recovery, the hernia was repaired successfully performing the Lichtenstein procedure. PMID- 17867610 TI - [Generalized fulminant descending paresis]. AB - We report the case of an 83-year-old female patient with fulminant tetraparesis and respiratory failure who required mechanical ventilation. After exclusion of some important differential diagnosis we gave antitoxin under the presumptive diagnosis of botulism. The clinical suspicion was confirmed by the serological detection of botulinum toxin. The patient showed six months after the onset of the disease a little improvement of the tetraparesis and was intermittent ventilator-dependent. In the commentary we discuss, basing on the literature, some important epidemiological, microbiological, clinical and therapeutically clues. PMID- 17867611 TI - [A rare case of cornu cutaneum]. PMID- 17867612 TI - How herbal remedies affect clinical laboratory test results. PMID- 17867613 TI - Healthcare in urban slums in India. PMID- 17867614 TI - Are the urban poor vulnerable to non-communicable diseases? A survey of risk factors for non-communicable diseases in urban slums of Faridabad. AB - BACKGROUND: Non-communicable diseases have modifiable risk factors, which are easy to measure and can help in planning effective interventions. We established a community-based sentinel surveillance to estimate the prevalence and level of common risk factors for major non-communicable diseases as part of a joint Indian Council of Medical Research/WHO initiative. METHODS: This survey was done from February 2003 to June 2004 and included 1260 men and 1 304 women 15-64 years of age living in urban slum areas of Ballabgarh block, Faridabad district, Haryana. A list of all slums in Ballabgarh block was obtained from the Municipal Corporation of Faridabad. Slums were selected by stratified cluster sampling. All households in the selected slums were visited and men and women interviewed in alternate households. The study instrument was based on the STEPS approach of WHO. It included questions related to tobacco use, alcohol intake, diet, physical activity, and history of treatment for hypertension and diabetes mellitus. Height, weight, waist circumference and blood pressure were measured. To estimate prevalence at the population level, age adjustment was done using the urban Faridabad population structure from the 2001 Census of India. RESULTS: The age adjusted prevalence of smoking among men was 36.5% compared with 7% in women. Bidi was the predominant form of smoked tobacco used. The use of smokeless tobacco was reported by 10.2% of men and 2.9% of women. While 26% of men reported consuming alcohol in the past 1 year, none of the women did. The mean number of servings per day of fruits and vegetables was 2.7 for men compared with 2.2 for women. Overall, only 7.9% and 5.4% of men and women, respectively took > or = 5 servings per day of fruits and vegetables. Women were more likely to be physically inactive compared with men (14.8% v. 55%); 67% of men and 22.8% of women reported mean physical activity > 150 minutes per week. The mean body mass index (BMI) was lower in men than in women (20.9 v. 21.9 kg/m2). The prevalence of overweight (BMI > or = 25 kg/m2)) was 16% among men and 21.9% among women. The prevalence of hypertension (blood pressure > or = 1 40/> or = 90 mmHg or on an antihypertensive drug) was 17.2% in men and 15.8% in women. CONCLUSION: The high prevalence of risk factors for noncommunicable diseases across all age groups in this urban slum community indicates the likelihood of a high future burden of illness. Immediate action for prevention and control is required to prevent the situation from worsening. PMID- 17867615 TI - Melphalan and dexamethasone for patients with multiple myeloma who are not candidates for autologous stem cell transplantation. AB - BACKGROUND: Multiple myeloma is a disease for which a number of treatment options are available. The choice of therapy is often based on factors such as cost, ease of administration and faster response as the survival rates are similar with most of the regimens. We assessed the efficacy of a combination of melphalan and dexamethasone as first-line therapy in patients with multiple myeloma who were not candidates for autologous stem cell transplantation. METHODS: Thirty-four patients with multiple myeloma were included in the study. Patients received a maximum of 12 cycles of chemotherapy consisting of oral melphalan 8 mg/m2 on days 1-4 and oral dexamethasone 40 mg on days 1-4 and days 9-12 every 4 weeks. Patients were assessed for response on the basis of M proteins and a bone marrow biopsy with touch preparation. RESULTS: The median follow up of surviving patients was 40 months. Nine patients (26.1%) had complete response/near complete response (5 had negative immunofixation) and 15 (44%) had partial response. The regimen was well tolerated and there were no therapy-related deaths. The 3-year overall and progression-free survival rates using the Kaplan-Meier method were 53% and 34%, respectively. The median duration of overall and progression-free survivals were 58 and 28 months, respectively. CONCLUSION: The combination of melphalan and dexamethasone is safe and effective in patients with multiple myeloma who are not candidates for autologous stem cell transplantation. PMID- 17867616 TI - Changing profile of disease contributing to mortality in a resettlement colony of Delhi. AB - BACKGROUND: The past decade has seen a decline in the disability-adjusted life years (DALYs) contributed by communicable diseases while lifestyle changes and rapid urbanization have led to an increase in DALYs contributed by non communicable diseases. We studied the causes of death in a low socioeconomic area over 11 years to help identify changes in the pattern of disease. METHODS: We did this study in Gokulpuri, a resettlement colony in East Delhi. All deaths occurring from 1994 to 2004 were analysed using a verbal autopsy questionnaire completed by trained health workers during their home visits in the area. RESULTS: A total of 515 deaths occurred during the period; 340 in men (66%) and 175 in women (34%). The six commonest causes of death were tuberculosis (24.8%), chronic obstructive pulmonary disease (11.6%), pneumonia (8.7%), accidents and poisoning (8.6 %), coronary heart disease (8.2%) and cancer (4.6%). The age specific mortality rate was highest among people > 45 years of age. The cause specific mortality rate due to communicable diseases showed a decline while that due to non-communicable diseases showed a rising trend in all age groups. CONCLUSION: Our study shows the coexistence of communicable and non-communicable diseases in a low socioeconomic area with a rising trend in non-communicable diseases. Surveillance for risk factors of non-communicable diseases should be done even in predominantly low socioeconomic areas. The coexistence of communicable and non-communicable diseases and the increase in non-communicable diseases among the economically deprived sections of our society suggest the need to re-prioritize components of healthcare among these sections. PMID- 17867617 TI - Haematopoietic stem cell transplantation: current status. AB - Haematopoietic stem cell transplantation (HSCT) is now an established treatment fora number of non-malignant and malignant conditions. Bone marrow- or peripheral blood-derived allogeneic SCT from an HLA-identical sibling or matched unrelated donor cures more than half the patients with severe aplastic anaemia, thalassaemia major, congenital immunodeficiency diseases and genetic metabolic disorders. Among the malignant conditions, acute and chronic leukaemia, multiple myeloma, Hodgkin and non-Hodgkin lymphoma, and high risk neuroblastoma are important conditions that can be treated by HSCT. The major morbidities associated with HSCT are regimen-related toxicities, development of acute or chronic graft-versus-host disease (GVHD), failure of engraftment of the bone marrow and complications related to the immunodeficiency that occurs in the post transplant period. Peripheral blood stem cells are now being used as an alternative to bone marrow stem cells for allogeneic HSCT and exclusively for autologous HSCT. Reduced intensity conditioning for allogeneic HSCT has resulted in a lower frequency and severity of GVHD and risk of infections. This has resulted in allogeneic HSCT being done in older patients and for those with co morbid conditions. Patients with low grade Hodgkin and non-Hodgkin lymphoma, chronic lymphocytic leukaemia and multiple myeloma appear to benefit more with this approach. Prevention of acute GVHD while maintainingthe graft-versus-tumour effect and close monitoring of the kinetics of chimerism hold promise for improving the outcome of those receiving reduced intensity allogeneic HSCT. In recipients ofautologous HSCT, identification of patients at increased risk for relapse and use of agents (interferon, interleukin-2) post-transplant to augment the graft-versus-tumour effect are possible areas of further research. PMID- 17867618 TI - Oral fluid-based rapid HIV 1/2 antibody test. PMID- 17867619 TI - Payments for healthcare: do they aggravate poverty? PMID- 17867620 TI - Nutrition therapy and exercise. PMID- 17867621 TI - It is time to wash the linen. AB - The unethical practice of commissions in private healthcare requires an open debate since it leads to expensive and hazardous healthcare. Doctors are accused of being sales agents and law breakers, private hospitals resemble luxury hotels, the consumer has become fair game whenever he/she has money, and our profession and society are rendered insensitive to human suffering. At the root of this malaise is the unplanned promotion of healthcare as a free market product. This very complex product, which is required in times of stress and vulnerability, has been institutionalized as a business for profiteering in the absence of adequate checks and balances. The product is inherently unsuited for the free market because the consumer cannot be king unless he is empowered to choose wisely. Not enough has been done to address this deficiency. Efforts are required to strengthen non-profit health facilities; to make the consumer wise and minimize her/his exposure to doctored health information. The present unethical practices of our profession are not the fault of doctors or the Medical Council of India, and punitive measures would be inappropriate. We should start with the creation of a government health website which educates the public about modern healthcare, and by regulating advertisement of health products. Since health personnel, officials and news media are directly benefited by the present malpractices, corrective will require consumer participation. PMID- 17867622 TI - Dialysis dilemmas. PMID- 17867623 TI - Don't forget public health! PMID- 17867624 TI - The nephrotoxicity of the Tsunami. PMID- 17867625 TI - Male circumcision: perspectives of doctors in southern India. PMID- 17867626 TI - Shortage of faculty in medical colleges: the solution might lie in sharing resources over the short-term. PMID- 17867627 TI - The entrance examination fiasco in Tamil Nadu. PMID- 17867628 TI - Effectiveness of laparoscopic approach for acute appendicitis. AB - BACKGROUND: Whether a laparoscopic approach is more effective for acute appendicitis than standard open appendectomy remains controversial. METHODS: Clinical records of the 95 consecutive patients who underwent appendectomy for acute appendicitis between April 2002 and December 2005 were reviewed retrospectively. Laparoscopic appendectomy was performed for 62 patients (LA group), while 33 underwent open appendectomy (OA group). At our institution, LA is a standard operative procedure for acute appendicitis, and OA underwent because of social reasons. Characteristics, operative factors, and postoperative course were compared between groups. RESULTS: Age, gender, past appendicitis attacks managed conservatively, and preoperative white blood cell counts did not differ significantly. Pathologic severity of appendicitis was more advanced in the OA than LA group (gangrenous in 52% vs 21% respectively, p=0.009). Mean operative time was significantly longer in the LA than OA group (80 min vs 63 min respectively, p=0.012). Pre- and postoperative white blood cell counts did not differ between groups, but recovery from postoperative pain and fever was significantly earlier in the LA than OA group (p=0.0007 and 0.013, respectively). Postoperative wound infection was significantly less frequent in the LA (6%) than OA group (27%, p=0.01), while incidence of postoperative intraabdominal infection did not differ significantly. Two patients in the LA group had serious complications that required reoperation; postoperative bleeding from the coagulated mesoappendix in one, and perforation of the jejunum caused by electrocautery during trocar insertion in the other. Mean postoperative hospital stay was significantly shorter in the LA than OA group (6.7 and 14.4 days respectively, p=0.04). According to severity of appendicitis, LA had no advantages over OA for gangrenous appendicitis. CONCLUSIONS: Laparoscopic appendectomy has some disadvantages, such as long operative time and possible of serious complications, but generally accelerates postoperative early recovery to shorten hospitalization. PMID- 17867629 TI - Pre-ischemic administration of landiolol prevents ischemia-reperfusion injury in the rat heart. AB - BACKGROUND: This study was designed to investigate whether administration of landiolol before or during ischemia protects the myocardium against ischemia reperfusion (I/R) injury. METHODS: Isolated rat hearts were perfused with Krebs Henseleit buffer using Langendorff apparatus. Cardiac arrest was achieved using St. Thomas' Hospital cardioplegic solution for 3 min. Each heart was subjected to global ischemia at 37 degrees C for 45 min followed by reperfusion for 60 min. In protocol A, landiolol (5-200 microM) was administered before ischemia and in protocol B, landiolol (10-1000 microM) was administered during ischemia. Post ischemic recovery of cardiac function after 60 min of reperfusion was expressed as a percentage of the pre-ischemic value. Creatinine kinase (CK) leakage during reperfusion for 20 min was also measured. RESULTS: Post-ischemic recovery of cardiac function and CK leakage were significantly improved by administration of 100 microM landiolol in protocol A (left ventricular developed pressure, 54.5 +/- 10.5% vs 76.1 +/- 6.6%; dP/dtmax, 47.5 +/- 14.9% vs 71.4 +/- 6.9%; coronary flow, 68.5 +/- 7.1% vs 83.9 +/- 12.9%, and CK, 25.3 +/- 4.2 IU vs 20.3 +/- 7.4 IU). In protocol B, landiolol exerted no cardioprotective effect on cardiac function and CK leakage at each concentration. CONCLUSIONS: Landiolol has a cardioprotective effect on I/R injury in the rat heart when administered before ischemia. PMID- 17867630 TI - The effect of ultrapure dialysate on improving renal anemia. AB - BACKGROUND: Renal anemia is a very serious problem in hemodialysis patients. In this regard, the investigation was focused on whether ultrapure dialysate could improve renal anemia and the mechanism of renal anemia. METHODS: Ultrapure dialysate was used over a 2 years period for 61 patients on maintenance hemodialysis. During this period, the changes in renal anemia and red blood cell life span were investigated. The changes in the latter were evaluated using the creatine concentration in red blood cell. RESULTS: The hemoglobin concentration, RBC count, and hematocrit concentration before the use of the ultrapure dialysate were 9.1 +/- 0.2 g/dL, 309.9 +/- L7.2 x 10(4)/microL, and 28.8 +/- 0.6%, respectively. These values significantly increased to 10.2 +/- 0.1 g/dL, 349.7 +/ 5.6 x 10(4)/microL, and 32.6 +/- 0.3%, respectively, after 2 years of ultrapure dialysate use. The increase in reticulocyte count indicated enhanced erythropoiesis by ultrapure dialysate. The red blood cell life span evaluated by creatine concentration in red blood cell was also prolonged after the use of ultrapure dialysate. CONCLUSIONS: Ultrapure dialysate is considered to improve the renal anemia of dialysis patients by promoting erythropoiesis and prolonging red blood cell life span. PMID- 17867631 TI - Effects of tiotropium or combined therapy with salmeterol on hyperinflation in COPD. AB - BACKGROUND: Hyperinflation is widely accepted as an abnormal state affecting clinical symptoms, activities of daily living and exercise tolerance in chronic obstructive pulmonary disease (COPD). Reducing hyperinflation is an essential theme in COPD treatment. In this study, we let patients with COPD hyperventilate to evoke hyperinflation, and evaluated the effects of tiotropium alone or in combination with salmeterol on hyperventilation-evoked hyperinflation. METHODS: Thirty-eight patients with COPD received pulmonary function tests including hyperventilation-evoked hyperinflation testing and the St. George's Respiratory Questionnaire (SGRQ) before treatment, after tiotropium administration for 8 weeks, and after combined therapy with salmeterol for 8 weeks. RESULTS: Before treatment, inspiratory capacity (IC) after hyperventilation decreased significantly in a breathing frequency-dependent manner. After tiotropium administration, forced expiratory volume in one second (FEV1) increased significantly. IC after hyperventilation decreased significantly in a breathing frequency-dependent manner; however, IC was significantly greater than that before treatment (at rest, p=0.001; after hyperventilation at twice the resting respiratory rate, p=0.0009; and after hyperventilation at three times the resting respiratory rate, p<0.0001). The SGRQ score also improved significantly. After combined therapy with salmeterol, FEV1 increased significantly compared with after tiotropium alone. However, there was no significant difference between the IC after tiotropium alone and that after combined therapy, at each stage. However, after combined therapy the SGRQ score significantly improved compared with that after tiotropium alone. CONCLUSIONS: Tiotropium improved airflow obstruction and hyperventilation-evoked hyperinflation. In combination with salmeterol, the improvement in airflow obstruction was greater, but hyperventilation-evoked hyperinflation was not further improved. PMID- 17867632 TI - Digital image analysis of choroidal hypoperfusion in indocyanine green angiography using a choroid to disc gray-scale ratio. AB - PURPOSE: To investigate hypoperfusion of the choroidal circulation in the macula, the brightness of the diffuse fluorescence of indocyanine green (ICG) angiogram (IA) was measured and the ratio of brightness of the macula to that of the disc was used for comparison of choroidal perfusion between different angiograms. METHODS: Ten eyes of 10 young volunteers under 30 years of age (17-28 years old, average 24.7 years old), 10 eyes of 10 old volunteers over 60 years old (60-78 years old, average 66.7 years old) and 5 eyes of 5 patients with age-related macular degeneration (AMD) were examined by IA. The angiograms at 4 and 16 seconds after dye filling were used to measure the brightness of diffuse fluorescence at the macula and the disc on ICG angiograms with a 256-grade gray scale using the Topcon IMAGEnet computer system. The ratio (ch/d ratio) of the averaged brightness of the macula to that of the disc was calculated for each angiogram. RESULTS: The ch/d ratios of the angiograms 4 seconds after dye filling were 1.41 in the young volunteers, 1.23 in the old volunteers and 0.52 in the AMD patients. The ch/d ratios of the angiograms 16 seconds after dye filling were 0.92 in the young volunteers, 1.02 in the old volunteers and 0.80 in AMD. There were significant differences in the ch/d ratios among the 3 groups 4 seconds after dye filling (p=0.007, Kruskal-Wallis H test,) but there were no significant differences 16 seconds after dye filling (p=0.310). CONCLUSION: The ch/d ratio is an adjunctive method for detecting choroidal hypoperfusion in IA, and may be helpful for objective evaluation of the choroidal circulation in chorioretinal diseases. PMID- 17867633 TI - Iris prolapse after non-penetrating trabeculectomy with sinusotomy and mitomycin C. AB - Non-penetrating trabeculectomy (NPT) is effective in preventing numerous postoperative complications encountered with trabeculectomy. Recently, NPT has been modified to further reduce intraocular pressure (IOP) by combining other techniques. However, these modified NPT methods would make the globe even weaker than NPT alone. Here, we report a case of iris prolapse caused by blunt ocular trauma after NPT with sinusotomy and mitomycin C treatment. A 68-year-old man, who underwent NPT with sinusotomy and mitomycin C treatment, suffered from blunt ocular trauma to his left eye 28 days after surgery. The iris prolapsed from the sinusotomy site. Iridectomy, scleral suturing, and pars plana vitrectomy were performed. The bleb was absent post-re-operatively. Iris prolapse occurs uncommonly following simple NPT. However, additional sinusotomy and mitomycin C treatment render the globe weaker, and iris prolapse might occur. Iris prolapse increases risks in developing secondary infections and a loss of the filtration bleb. Thus, precautions are needed postoperatively. PMID- 17867634 TI - Capillary electrophoresis is essential for microsatellite marker based detection and quantification of adulteration of Basmati rice (Oryza sativa). AB - Microsatellite markers are employed for genotyping of Basmati varieties and assaying purity of market samples. However, employment of diverse electrophoresis techniques across laboratories has resulted in inconsistent allele sizes, creating doubts about the suitability of the assay. This study evaluated agarose gel electrophoresis, slab gel electrophoresis, and capillary electrophoresis techniques for their efficiency in the detection and quantification of adulteration in Basmati samples. Comparative analysis across 8 microsatellite loci in 12 rice varieties demonstrated that the capillary electrophoresis method showed less error (+/-0.73 bp) in the estimation of allele sizes compared to slab gel (+/-1.59 bp) and agarose gel (+/-8.03 bp) electrophoretic methods. Capillary electrophoresis showed greater reproducibility (<0.5 bp deviation) compared to slab gel (1 bp) and agarose (>3 bp) based methods. Capillary electrophoresis was significantly superior in quantification of the adulterant, with a mean error of +/-3.91% in comparison to slab gel (+/-6.09%). Lack of accuracy and consistency of the slab gel and agarose electrophoretic methods warrants the employment of capillary electrophoresis for Basmati rice purity assays. PMID- 17867635 TI - Flavonoid and hydroxycinnamate profiles of english apple ciders. AB - Seventeen phenolic compounds in 23 English apple ciders were identified and quantified by HPLC-PDA-MS (2). The total phenolic content of the ciders varied greatly ranging from 44 to 1559 mg/L. Four groups of compounds were identified, flavan-3-ols, hydroxycinnamates, flavonols, and dihydrochalcones. Hydroxycinnamates were the predominant group of phenolics in the majority of the ciders. Procyanidins were analyzed by HPLC after thiolysis, and total procyanidin content ranged from 8 to 722 mg/L and an average degree of polymerization of 2.5 3.5. This investigation of a wide range of ciders has shown a substantial variation in the profile and quantity of the phenolics. The analysis of single variety ciders highlighted the importance of using an apple cultivar with a high phenolic content to produce a phenolic-rich cider. Adaptations to the cider making process could be used to increase the phenolic content with potential health benefits. PMID- 17867636 TI - Characterization of alpha-terpineol as an anti-inflammatory component of orange juice by in vitro studies using oral buccal cells. AB - Epithelial buccal cells (KB) were exposed to orange juice or orange juice fractions containing either the dry matter (DM), the volatile compounds (aqueous distillate, AD), or individual nonvolatile or volatile components. Intracellular formation of the pro-inflammatory cytokine IL-6 was analyzed by flow cytometry. Exposure to whole orange juice resulted in an increase in IL-6 formation of 23% compared to nontreated control cells, whereas treatment of the cells with either DM or AD resulted in a 22 or 1% increase, respectively. Dose-response experiments revealed that exposure of the cells to a 2- or 4-fold concentrated AD resulted in an increased IL-6 formation, whereas an inhibiting effect was measured after treatment of the cells with an 8-fold concentrated AD. These results indicated the presence of pro- as well as anti-inflammatory compounds in the aqueous distillate. To identify the active principles, volatile compounds present in the AD-treated cells were analyzed by GC-MS. In particular, limonene, linalool, and alpha-terpineol were shown to be present in significant amounts. Subsequent studies on the IL-6 formation revealed that limonene had a stimulating effect and alpha-terpineol had an inhibiting effect, whereas linalool had no effect. This anti-inflammatory effect of alpha-terpineol on IL-6 formation was verified by quantitative real-time reverse transcription Polymerase Chain Reaction experiments in which alpha-terpineol inhibited the gene expression of the IL-6 receptor. PMID- 17867637 TI - Flavonoids in horse chestnut (Aesculus hippocastanum) seeds and powdered waste water byproducts. AB - Horse chestnut extracts are widely used in pharmacy and cosmetic industries. The main active constituents are saponins of oleane type, but seeds of horse chestnut also contain flavonoids, being glycosides of quercetin and kaempferol. Their contribution to the overall activity of the extracts was not clear. In the present work, the main flavonoids from horse chestnut seeds were isolated and their structures established with spectral methods. Seven glycosides were isolated, out of which six ( 2, 3, 4, 7, 11, 13) were previously reported and one ( 9) was identified as a new tamarixetin 3- O- [beta- d-glucopyranosyl(1-->3)]- O beta- d-xylopyranosyl-(1-->2)- O-beta- d-glucopyranoside. The structures of three additional compounds 1, 10, and 12, not previously reported, were deduced on the basis of their LC-ESI/MS/MS fragmentation characteristics. A new ultraperformance liquid chromatographic (UPLC) method has been developed for profiling and quantitation of horse chestnut flavonoids. The method allowed good separation over 4.5 min. Thirteen compounds could be identified in the profile, out of which di- and triglycoisdes of quercetin and kaempferol were the dominant forms and their acylated forms occurred in just trace amounts. The total concentration of flavonoids in the powdered horse chestnut seed was 0.88% of dry matter. The alcohol extract contained 3.46%, and after purification on C18 solid phase, this concentration increased to 9.40% of dry matter. The flavonoid profile and their content were also measured in the horse chestnut wastewater obtained as byproduct in industrial processing of horse chestnut seeds. The total flavonoid concentration in the powder obtained after evaporation of water was 2.58%, while after purification on solid phase, this increased to 11.23% dry matter. It was concluded that flavonoids are present in a horse chestnut extract in a relatively high amount and have the potential to contribute to the overall activity of these extracts. Industrial horse chestnut wastewater can be used to obtain quercetine and kaempferol glycosides for cosmetic, nutraceutical, and food supplement industries. PMID- 17867638 TI - Almond (Prunus dulcis (Mill.) D.A. Webb) skins as a potential source of bioactive polyphenols. AB - An exhaustive study of the phenolic composition of almond ( Prunus dulcis (Mill.) D.A. Webb) skins was carried out in order to evaluate their potential application as a functional food ingredient. Using the HPLC-DAD/ESI-MS technique, a total of 33 compounds corresponding to flavanols, flavonols, dihydroflavonols and flavanones, and other nonflavonoid compounds were identified. Peaks corresponding to another 23 structure-related compounds were also detected. MALDI-TOF MS was applied to characterize almond skin proanthocyanidins, revealing the existence of a series of A- and B-type procyanidins and propelargonidins up to heptamers, and A- and B-type prodelphinidins up to hexamers. Flavanols and flavonol glycosides were the most abundant phenolic compounds in almond skins, representing up to 38 57% and 14-35% of the total quantified phenolics, respectively. Due to their antioxidant properties, measured as oxygen-radical absorbance capacity (ORAC) at 0.398-0.500 mmol Trolox/g, almond skins can be considered as a value-added byproduct for elaborating dietary antioxidant ingredients. PMID- 17867639 TI - Development of an enzyme-linked immunosorbent assay to detect an immunomodulatory alpha-D-glucan-protein complex, MPG-1, in basidiomycete Tricholoma matsutake and related processed foods. AB - We previously isolated a novel immunomodulatory alpha-(1,4)(1,6)(1,2)- d-glucan protein complex (MPG-1) from mycelia of Tricholoma matsutake in basidiomycetes. In the present study, we raised a polyclonal antibody by immunizing rabbits with MPG-1 and constructed a sandwich enzyme-linked immunosorbent assay (ELISA) system to examine the distribution of MPG-1 among edible mushrooms and related processed foods. The system detected MPG-1 quantitatively at concentrations of more than 10 ng/mL, with a coefficient of variation of less than 10% by intra-assay and interassay precision. Analysis with the system of chemically modified MPG-1 suggested that the sugar moiety was mainly involved in the detection. The system detected MPG-1 in the extracts of the fruiting bodies of T. matsutake but not in those of 34 other basidiomycete species. Moreover, a significant amount of MPG-1 was detected in the extracts of their cultured mycelia. The antigenic structure of MPG-1 was relatively stable in terms of pH and temperature. MPG-1 was detected in processed foods supplemented with T. matsutake. These results suggest that MPG 1 is distributed predominantly in T. matsutake species and that the ELISA system can detect it in processed foods supplemented with T. matsutake. PMID- 17867640 TI - Comparative study of antimicrobial peptides to control citrus postharvest decay caused by Penicillium digitatum. AB - The objective of this study was to investigate and compare the in vitro efficacy and in vivo potential of eight distinct short antimicrobial peptides to control the postharvest green mold disease of oranges caused by the fungus Penicillium digitatum. The L-amino acid versions of the four peptides PAF26, PAF38, PAF40, and BM0, previously obtained by combinatorial approaches, were examined. The study included two antibacterial peptides formerly identified by rational design, BP15 and BP76, and it is demonstrated that they also have in vitro antifungal properties. The natural antimicrobial peptides melittin and indolicidin were also selected for comparison, due to their well-known properties and modes of action. In vitro and in vivo results indicated differential behaviors among peptides, regarding the inhibitory potency in growth media, selectivity against distinct microorganisms, fungicidal activity towards nongerminated conidia of P. digitatum, and efficacy in fruit inoculation assays. Interestingly, a high in vitro inhibitory activity did not necessarily associate with an effective control of fruit infection by P. digitatum. The short tryptophan-rich cationic peptides PAF26, PAF38, PAF40, and BM0 were lethal to conidia of P. digitatum, and this property is correlated with better protection in the decay control test. PMID- 17867641 TI - Metabolic characterization of newly isolated Pseudomonas nitroreducens Jin1 growing on eugenol and isoeugenol. AB - Newly isolated soil bacterium strain Jin1 was able to grow on both eugenol and isoeugenol each as sole source of carbon and energy. Based on bacterial 16S rDNA analysis, Jin1 belongs to Pseudomonas nitroreducens with a similarity of 98.92% (14/1297). P. nitroreducens Jin1 was found to biotransform eugenol and isoeugenol to vanillin by different pathways. Eugenol was biotransformed to vanillin through coniferyl alcohol and ferulic acid similarly to the pathway shown previously by Pseudomonassp. HR199 and vanillin produced from eugenol was rapidly metabolized to vanillic acid. Contrastively, Pseudomonas nitroreducens Jin1 did not appear to produce metabolic intermediates during the biotransformation of isoeugenol to vanillin which was finally biotransformed to vanillic acid with much slower rate. These results indicate that there seems to be different metabolic regulation systems for the biotransformation of eugenol and isoeugenol by this bacterium. Herein, we report on Pseudomonas nitroreducens Jin1, a novel bacterium that produces vanillin from eugenol and isoeugenol by two different metabolic pathways. PMID- 17867642 TI - Sisal fibers: surface chemical modification using reagent obtained from a renewable source; characterization of hemicellulose and lignin as model study. AB - Sisal fibers have one of the greatest potentials among other lignocellulosic fibers to reinforce polymer matrices in composites. Sisal fibers have been modified to improve their compatibility with phenolic polymer matrices using furfuryl alcohol (FA) and polyfurfuryl alcohols (PFA) that can be obtained from renewable sources. The modification corresponded first to oxidation with ClO 2, which reacts mainly with guaiacyl and syringyl units of lignin, generating o- and p-quinones and muconic derivatives, followed by reaction with FA or PFA. The FA and PFA modified fibers presented a thin similar layer, indicating the polymer character of the coating. The untreated and treated sisal fibers were characterized by (13)C CP-MAS NMR spectrometry, thermal analysis, and scanning electron microscopy. Furthermore, for a better understanding of the reactions involved in the FA and PFA modifications, the sisal lignin previously extracted was also submitted to those reactions and characterized. The characterization of isolated lignin and hemicellulose provides some information on the chemical structure of the main constitutive macrocomponents of sisal fibers, such information being scarce in the literature. PMID- 17867643 TI - Molecular and thermodynamic aspects of solubility advantage from solid dispersions. AB - The solubility behavior of solid dispersions of two drugs with similar structures was studied. Valdecoxib (VLB) and etoricoxib (ETB) were used as model drugs, and their solid dispersions were prepared with 1, 2, 5, 10, 15, and 20% w/w poly(vinylpyrrolidone) (PVP) by the quench cooling method. The interactions between the drug and polymer molecules were studied by Fourier transform infrared spectroscopy (FT-IR). The thermodynamic aspects of solubility behavior were studied by plotting van't Hoff plots. Both the drugs showed significant differences in their solubility behavior. In the case of VLB, solubility was found to increase significantly with increasing PVP concentration. ETB however did not show any significant solubility enhancement and was found to have decreased solubility at high PVP concentrations. H-bonding interactions were established between VLB and PVP molecules, while none were observed in ETB-PVP dispersions. Solution thermodynamics of amorphous and crystalline forms of both the drugs were studied by van't Hoff plots. The results obtained showed very high negative value of Gibbs free energy for VLB as compared to ETB, thus demonstrating high spontaneity of VLB solubilization. Entropy of amorphous VLB was found to be highly favorable, while being slightly unfavorable for ETB. From this study H-bonding interactions were found to play a major role in dictating the solubility behavior of these drugs from solid dispersions. PMID- 17867644 TI - Apoptotic epidermal growth factor (EGF)-conjugated block copolymer micelles as a nanotechnology platform for targeted combination therapy. AB - The overexpression of epidermal growth factor receptor (EGFR) in human epithelial cancers has been associated with aggressive disease, poor patient prognosis, and a high incidence of metastases. In the present study, block copolymer micelles are conjugated with epidermal growth factor (EGF), which acts as both a targeting ligand for the drug carrier and an apoptotic factor against EGFR-overexpressing cancers. Drug-free EGF-conjugated micelles are shown to result in cell-cycle arrest at the G 1 phase and subsequent induction of cell-type-specific apoptosis in EGFR-overexpressing breast cancer cells as demonstrated by flow cytometric analysis. EGF delivered as EGF-conjugated micelles was found to be 13-fold more potent than free EGF; the IC 50 was decreased from 0.98 +/- 0.1 nM for free EGF to 0.076 +/- 0.01 nM for EGF micelles. The apoptotic micelles, however, are non antiproliferative to cells expressing a low level of EGFR, suggesting that the apoptotic micelles have minimal or no toxicity against normal healthy tissues. Ellipticine, a chemotherapeutic agent, was loaded into the EGF-micelles after it had been shown, using the combination index-isobologram equation, to act synergistically with EGF. A 10-fold increase in EGF content in the ellipticine loaded micelles lowered the IC 50 of ellipticine in EGFR-overexpressing breast cancer cells by more than 18-fold. The EGF-micelles have the potential to be further pursued as a versatile nanotechnology platform for targeted delivery of a wide range of chemotherapeutic agents as a combination therapy for the treatment of EGFR-overexpressing cancers. PMID- 17867645 TI - Expedient Lewis acid catalyzed synthesis of a 3-substituted 5-arylidene-1-methyl 2-thiohydantoin Library. AB - An efficient and rapid solution phase combinatorial synthesis of a 3-substituted 5-arylidene-1-methyl-2-thiohydantoin library was developed. The salient feature for this library production procedure is the addition of the Lewis acid catalyst, indium(III) trifluoromethanesulfonate, which serves to facilitate the direct condensation of aldehydes with 3-substituted 1-methyl-2-thiohydantoins. Use of this Lewis acid catalyst has resulted in faster reaction times, higher conversions and better purity profiles for these condensation reactions as compared to traditional uncatalyzed reactions. The resulting 315 member library of 3-substituted 5-arylidene-1-methyl-2-thiohydantoin is described. PMID- 17867646 TI - Identification of cytochrome P450 3A4 modification site with reactive metabolite using linear ion trap-Fourier transform mass spectrometry. AB - Covalent binding of reactive metabolites to cytochrome P450s (P450s) often causes their mechanism-based inactivation (MBI), resulting in drug-drug interactions or toxicity. The detection and identification of the P450 sites to which reactive metabolites bind would elucidate MBI mechanisms. We describe a proteomic approach using nano-LC/linear ion trap-Fourier transform ion cyclotron resonance (FTICR) mass spectrometry to characterize the binding of a reactive metabolite of raloxifene, which is a known P450 3A4 inhibitor, to the P450 3A4 isozyme. LTQ-FT analyses revealed that the metabolic reaction of raloxifene in a reconstituted P450 3A4 system formed a reactive metabolite adduct to P450 3A4 apoprotein, accompanied by a mass shift of 471 Da relative to intact P450 3A4 apoprotein. The reaction mixtures were digested with trypsin, and then the tryptic digests were analyzed by nano-LC-MS/MS. This technique revealed that VWGFYDGQQPVLAITDPDMIK (position 71-91) was a tryptic peptide modified by the reactive metabolite derived from raloxifene. The site of adduction with the reactive metabolite was further postulated to be the nucleophilic OH group of Tyr-75 of P450 3A4. A proteomic approach using LTQ-FT can yield direct information on the P450 3A4 modification site without radiolabeled compounds. In addition, this information can elucidate mechanisms involved in the covalent binding of reactive metabolites and the inactivation of P450 3A4. PMID- 17867647 TI - Sequence distribution of acetaldehyde-derived N2-ethyl-dG adducts along duplex DNA. AB - Acetaldehyde (AA) is the major metabolite of ethanol and may be responsible for an increased gastrointestinal cancer risk associated with alcohol beverage consumption. Furthermore, AA is one of the most abundant carcinogens in tobacco smoke and induces tumors of the respiratory tract in laboratory animals. AA binding to DNA induces Schiff base adducts at the exocyclic amino group of dG, N2 ethylidene-dG, which are reversible on the nucleoside level but can be stabilized by reduction to N2-ethyl-dG. Mutagenesis studies in the HPRT reporter gene and in the p53 tumor suppressor gene have revealed the ability of AA to induce G-->A transitions and A-->T transversions, as well as frameshift and splice mutations. AA-induced point mutations are most prominent at 5'-AGG-3' trinucleotides, possibly a result of sequence specific adduct formation, mispairing, and/or repair. However, DNA sequence preferences for the formation of acetaldehyde adducts have not been previously examined. In the present work, we employed a stable isotope labeling-HPLC-ESI+-MS/MS approach developed in our laboratory to analyze the distribution of acetaldehyde-derived N2-ethyl-dG adducts along double stranded oligodeoxynucleotides representing two prominent lung cancer mutational "hotspots" and their surrounding DNA sequences. 1,7,NH 2-(15)N-2-(13)C-dG was placed at defined positions within DNA duplexes derived from the K-ras protooncogene and the p53 tumor suppressor gene, followed by AA treatment and NaBH 3CN reduction to convert N2-ethylidene-dG to N2-ethyl-dG. Capillary HPLC ESI+-MS/MS was used to quantify N2-ethyl-dG adducts originating from the isotopically labeled and unlabeled guanine nucleobases and to map adduct formation along DNA duplexes. We found that the formation of N2-ethyl-dG adducts was only weakly affected by the local sequence context and was slightly increased in the presence of 5-methylcytosine within CG dinucleotides. These results are in contrast with sequence-selective formation of other tobacco carcinogen-DNA adducts along K-ras- and p53-derived duplexes and the preferential modification of endogenously methylated CG dinucleotides by benzo[a]pyrene diol epoxide and acrolein. PMID- 17867648 TI - Synthesis and characterization of styrene oxide adducts with cysteine, histidine, and lysine in human globin. AB - Styrene 7,8-oxide (SO), a reactive metabolic intermediate of the industrial chemical styrene, binds covalently at nucleophilic amino acid residues of blood proteins in vivo and in vitro. In this study, SO adducts with cysteine, lysine, and histidine were synthesized, characterized, and then used as authentic standards to assign and quantitate the SO adducts in globin incubated with SO. S (2-Hydroxy-1-phenylethyl)cysteine and S-(2-hydroxy-2-phenylethyl)cysteine were prepared by direct alkylation of cysteine with (R)-SO or (S)-SO. To prepare the SO adducts with lysine and histidine, Nalpha-Boc-protected amino acids were alkylated with (R)-SO or (S)-SO followed by deprotection of the Boc group to obtain Nepsilon-(2-hydroxy-1-phenylethyl)lysine and Nepsilon-(2-hydroxy-2 phenylethyl)lysine as well as Npi-(2-hydroxy-1-phenylethyl)histidine, Npi-(2 hydroxy-2-phenylethyl)histidine, Ntau-(2-hydroxy-1-phenylethyl)histidine, and Ntau-(2-hydroxy-2-phenylethyl)histidine. The individual regioisomers were isolated from their mixtures by semipreparative HPLC, and their structure was assigned using NMR techniques. The SO-modified globin, isolated from human hemoglobin incubated in vitro with racemic SO at a molar ratio SO/globin of 100:1 or 10:1, was digested with pronase and subjected to LC/MS and GC/MS analysis. All known regioisomers of the SO adducts were detected, with S-(2-hydroxy-1 phenylethyl)cysteine, Nepsilon-(2-hydroxy-1-phenylethyl)lysine, and Ntau-(2 hydroxy-2-phenylethyl)histidine being the most abundant in the modified globin. Deuterated analogues of the SO adducts were employed as internal standards. The SO-amino acid adducts described here appear to be suitable biomarkers for long term exposures to styrene or SO. PMID- 17867649 TI - Functionalized carbon nanotubes in drug design and discovery. AB - Carbon nanotubes (CNTs) have been proposed and actively explored as multipurpose innovative carriers for drug delivery and diagnostic applications. Their versatile physicochemical features enable the covalent and noncovalent introduction of several pharmaceutically relevant entities and allow for rational design of novel candidate nanoscale constructs for drug development. CNTs can be functionalized with different functional groups to carry simultaneously several moieties for targeting, imaging, and therapy. Among the most interesting examples of such multimodal CNT constructs described in this Account is one carrying a fluorescein probe together with the antifungal drug amphotericin B or fluorescein and the antitumor agent methotrexate. The biological action of the drug in these cases is retained or, as in the case of amphotericin B constructs, enhanced, while CNTs are able to reduce the unwanted toxicity of the drug administered alone. Ammonium-functionalized CNTs can also be considered very promising vectors for gene-encoding nucleic acids. Indeed, we have formed stable complexes between cationic CNTs and plasmid DNA and demonstrated the enhancement of the gene therapeutic capacity in comparison to DNA alone. On the other hand, CNTs conjugated with antigenic peptides can be developed as a new and effective system for synthetic vaccine applications. What makes CNTs quite unique is their ability, first shown by our groups in 2004, to passively cross membranes of many different types of cells following a translocation mechanism that has been termed the nanoneedle mechanism. In that way, CNTs open innumerable possibilities for future drug discovery based on intracellular targets that have been hard to reach until today. Moreover, adequately functionalized CNTs as those shown in this Account can be rapidly eliminated from the body following systemic administration offering further encouragment for their development. CNT excretion rates and accumulation in organs and any reactivity with the immune system will determine the CNT safety profile and, consequently, any further pharmaceutical development. Caution is advised about the need for systematic data on the long-term fate of these very interesting and versatile nano-objects in correlation with the type of CNT material used. CNTs are gradually plyaing a bigger and more important role in the emerging field of nanomedicine; however, we need to guarantee that the great opportunities they offer will be translated into feasible and safe constructs to be included in drug discovery and development pipelines. PMID- 17867650 TI - Method for quantification of a prostate cancer biomarker in urine without sample preparation. AB - We describe a macrocantilever-based method for detecting a prostate cancer biomarker (alpha-methylacyl-CoA racemase; AMACR) directly in patient urine without a sample preparation step and without the use of labeled reagents. Clean catch voided urine specimens were prospectively collected from five confirmed prostate cancer patients 3 weeks postbiopsy. The presence of AMACR was measured in a blinded manner by exposing 3 mL of urine to the anti-AMACR-immobilized piezoelectric-excited millimeter-sized (PEMC) sensor. The resonance frequency of PEMC decreases as AMACR from sample binds to the antibody on the sensor. The resonance frequency changes for the five patients tested were 4,314 +/- 35 (n = 2), 269 +/- 17 (n = 2), 977 +/- 64 (n = 3), 600 +/- 31 (n = 2), and 801 +/- 81 (n = 2) Hz, respectively. Positive detection was observed within approximately 15 min. The responses to positive, negative, and buffer controls were -9 +/- 13, -34 +/- 18, and -6 +/- 18 Hz, respectively. Positive verification of AMACR attachment was confirmed by low-pH buffer release. The sensor response was quantitatively related to AMACR concentration in control urine, and the relationship was used in developing an in situ calibration method for quantifying AMACR in patient urine. Estimated concentrations of 42, 2, and 3 fg/mL AMACR were calculated for the three patients' urine, while absence of AMACR was confirmed in control urine (n = 13). Because of simplicity of measurement combined with high sensitivity and specificity, the method may be a useful adjunct in a point-of-care setting to identify men at increased risk for prostate cancer. PMID- 17867651 TI - Non-gel-based dual 18O labeling quantitative proteomics strategy. AB - To improve the quantitation of target proteins in proteomic analyses, we developed a non-gel-based, dual (18)O labeling strategy. This global isotope labeling method utilizes an acylating chemical reagent with two anhydride functional groups, bicyclic anhydride diethylenetriamine-N,N,N', N' ',N' ' pentaacetic acid (DTPA) dianhydride. In the first (18)O labeling method (chemical (18)O labeling) of our dual strategy, one functional group was covalently coupled to the primary amines of the peptides and (18)O from H2(18)O was incorporated at the other functional group by hydrolysis. In the second (18)O labeling method (chemical and enzyme-catalyzed (18)O labeling), chemical (18)O labeling and enzyme-catalyzed (18)O labeling of the carboxyl- termini of the peptides were combined. The acylation reaction between DTPA and the model peptides was rapid and specific, and the DTPA-modified N-termini of the peptides promoted only y series ions in MS/MS. The two methods of (18)O labeling were accurate in the range 0.1-10 of (16)O/(18)O peptide ratios. The deviations of the methods were <20%. In contrast to current proteolytic (18)O labeling methods, there was no (18)O to (16)O back-exchange in the first method and no isotope peaks in MS in the second method. The combination of chemical and proteolytic (18)O labeling improved the confidence of the quantitation results. PMID- 17867652 TI - Design and synthesis of single-nanoparticle optical biosensors for imaging and characterization of single receptor molecules on single living cells. AB - At the cellular level, a small number of protein molecules (receptors) can induce significant cellular responses, emphasizing the importance of molecular detection of trace amounts of protein on single living cells. In this study, we designed and synthesized silver nanoparticle biosensors (AgMMUA-IgG) by functionalizing 11.6 +/- 3.5-nm Ag nanoparticles with a mixed monolayer of 11-mercaptoundecanoic acid (MUA) and 6-mercapto-1-hexanol (1:3 mole ratio) and covalently conjugating IgG with MUA on the nanoparticle surface. We found that the nanoparticle biosensors preserve their biological activity and photostability and can be utilized to quantitatively detect individual receptor molecules (T-ZZ), map the distribution of receptors (0.21-0.37 molecule/microm(2)), and measure their binding affinity and kinetics at concentrations below their dissociation constant on single living cells in real time over hours. The dynamic range of detection is 0-50 molecules per cell. We also found that the binding rate (2-27 molecules/min) is highly dependent upon the coverage of receptors on living cells and their ligand concentration. The binding association and dissociation rate constants and affinity constant are k1 = (9.0 +/- 2.6) x 10(3) M(-1) s(-1), k(-1) = (3.0 +/- 0.4) x 10(-4) s(-1), and KB = (4.3 +/- 1.1) x 10(7) M(-1), respectively. PMID- 17867653 TI - Ambient mass spectrometry with a handheld mass spectrometer at high pressure. AB - The first coupling of atmospheric pressure ionization methods, electrospray ionization (ESI) and desorption electrospray ionization (DESI), to a miniature hand-held mass spectrometer is reported. The instrument employs a rectilinear ion trap (RIT) mass analyzer and is battery-operated, hand-portable, and rugged (total system: 10 kg, 0.014 m(3), 75 W power consumption). The mass spectrometer was fitted with an atmospheric inlet, consisting of a 10 cm x 127 microm inner diameter stainless steel capillary tube which was used to introduce gas into the vacuum chamber at 13 mL/min. The operating pressure was 15 mTorr. Ions, generated by the atmospheric pressure ion source, were directed by the inlet along the axis of the ion trap, entering through an aperture in the dc-biased end plate, which was also operated as an ion gate. ESI and DESI sources were used to generate ions; ESI-MS analysis of an aqueous mixture of drugs yielded detection limits in the low parts-per-billion range. Signal response was linear over more than 3 orders of magnitude. Tandem mass spectrometry experiments were used to identify components of this mixture. ESI was also applied to the analysis of peptides and in this case multiply charged species were observed for compounds of molecular weight up to 1200 Da. Cocaine samples deposited or already present on different surfaces, including currency, were rapidly analyzed in situ by DESI. A geometry independent version of the DESI ion source was also coupled to the miniature mass spectrometer. These results demonstrate that atmospheric pressure ionization can be implemented on simple portable mass spectrometry systems. PMID- 17867654 TI - Oligonucleotide gas-phase hydrogen/deuterium exchange with D2S in the collision cell of a quadrupole-Fourier transform ion cyclotron resonance mass spectrometer. AB - We have implemented gas-phase hydrogen/deuterium exchange (HDX) experiments in the external collision cell of a hybrid quadrupole-Fourier transform ion cyclotron resonance mass spectrometer. In this configuration, multiply charged oligonucleotide anions undergo significant exchange with D(2)S at reaction intervals ranging from 0.11 to 60.1 s. For DNA homohexamers, relative exchange rates were dC(6) approximately dA(6) > dG(6) > dT(6), correlating with the gas phase acidities of nucleobases (C > A > T > G), except for guanine. Our results are consistent with a relay mechanism in which D(2)S interacts with both a backbone phosphate group and a neutral nucleobase through hydrogen bonding. We propose that the faster exchange of polyguanosine compared to polythymidine is due to the larger size of guanine and the orientation of its labile hydrogens, which may result in gas-phase conformations more favorable for forming complexes with D(2)S. Similar trends were observed for RNA homohexamers, although their HDX rates were faster than for DNA, suggesting they can also exchange via another relay process involving the 2'-hydroxyl group. HDX of DNA duplexes further supports the involvement of nucleobase hydrogens because duplexes exchanged slower than their corresponding single strands, presumably due to the intermolecular hydrogen bonds between nucleobases. This work constitutes the first investigation of the mechanisms of oligonucleotide gas-phase HDX. Our results on duplexes show promise for application of this strategy to the characterization of structured nucleic acids. PMID- 17867655 TI - Dual electrospray ion source for electron-transfer dissociation on a hybrid linear ion trap-orbitrap mass spectrometer. AB - A dual electrospray ionization source (ESI) has been modified to simultaneously produce cations and anions, one from each emitter, for performing rapid electron transfer dissociation (ETD) ion/ion reactions on a hybrid linear ion trap orbitrap mass spectrometer. Unlike the pulsed dual ESI sources that were used to generate ETD reagent ions, this source separates the emitters in space, rather than time, by physically switching which one is in front of the atmospheric inlet. The new arrangement allows for substantially enhanced spray stability and decreased switching times (total slightly deviates from the predicted linear behavior. The QENS data indicate that this deviation, which is virtually independent of the extent of hydration, is due to a partial onset of diffusive protein motions. (C) At temperatures above 240 K, the protein flexibility drastically changes because of the onset of diffusive (large-amplitude) protein motions. This dynamical transition is clearly hydration dependent since it is strongly suppressed in dry PS II. The thermally activated onset of protein flexibility as monitored by QENS is found to be strictly correlated with the temperature-dependent increase of the electron transport efficiency from Q(A)(-) to QB (Garbers et al. (1998) Biochemistry 37, 11399 11404). Analogously, the freezing of protein mobility by dehydration in dry PS II appears to be responsible for the blockage of Q(A)(-) reoxidation by Q(B) at hydration values lower than 45% r.h. (Kaminskaya et al. (2003) Biochemistry 42, 8119-8132). Similar effects were observed for reactions of the water-oxidizing complex as outlined in the Discussion section. PMID- 17867658 TI - Vibrational spectra and structure of CH3Cl:(H2O)2 and CH3Cl:(D2O)2 complexes. IR matrix isolation and ab initio calculations. AB - The infrared spectra of CH3Cl + H2O isolated in solid neon at low temperature have been investigated. High concentration studies of water (0.01%-4%) and subsequent annealing lead to the formation of the ternary CH3Cl:(H2O)2 complex. Detailed vibrational assignments were made on the observed spectra of water and deuterated water engaged in the complex. In parallel, structural, energetic, and vibrational properties of the complex have been studied at the second-order Moller-Plesset perturbation theory using several basis sets. Anaharmonic correction to the vibrational frequencies has been done with the standard second order perturbation approach. It was shown that the ground state of the complex has a cyclic form for which the nonadditive three-body contribution was found to be around 10% of the interaction energy. PMID- 17867659 TI - Femtosecond IR spectroscopy of peroxycarbonate photodecomposition: S1-lifetime determines decarboxylation rate. AB - The ultrafast photofragmentation of arylperoxycarbonates R-O-C(O)O-O-tert-butyl (R = naphthyl, phenyl) is studied using femtosecond UV excitation at 266 nm and mid-infrared broadband probe pulses to elucidate the dissociation mechanism. Our experiments show that the rate of fragmentation is determined by the S1-lifetime of the peroxide, i.e., the time constants of S1 decay and of CO2 and R-O* formation are identical. The fragmentation times are solvent dependent and for tert-butyl-2-naphthylperoxycarbonate (TBNC) vary from 25 ps in CH2Cl2 to 52 ps in n-heptane. In the case of the tert-butylphenylperoxycarbonate (TBPC) the decomposition takes 5.5 ps in CD2Cl2 and 12 ps in n-heptane. The CO2 fragment is formed vibrationally hot with an excess energy of about 5000 cm(-1). The hot CO2 spectra at high energy can be modeled assuming Boltzmann distributions with initial vibrational temperatures of ca. 2500 K which relax to ambient temperature with time constants of 280 ps in CCl4 and 130 ps in n-heptane. In CCl4 the relaxed spectra at 1.5 ns show 3.5% residual excitation in the n = 1 level of the asymmetric stretch vibration. PMID- 17867660 TI - Self-directed growth of contiguous perpendicular molecular lines on H-Si(100) surfaces. AB - Future nanoscale integrated circuits will require the realization of interconnections using molecular-scale nanostructures; a practical fabrication scheme would need to be largely self-assembling and operate on a large number of like structures in parallel. The self-directed growth of organic molecules on hydrogen-terminated silicon(100) [H-Si(100)] offers a simple method of realizing one-dimensional molecular lines. In this work, we introduce the ability to change the growth direction and form more complex, contiguous shapes. Numerous styrene and trimethylene sulfide L shapes were grown on a H-Si(100)-3x1 surface in parallel with no intermediate surface lithography steps, and similar shapes were also grown using allyl mercaptan and benzaldehyde on H-Si(100)-2x1. Registered scanning tunneling microscopy (STM) images and high-resolution electron energy loss spectroscopy (HREELS) were used to investigate the growth process. PMID- 17867661 TI - The CN stretching band of aliphatic thiocyanate is sensitive to solvent dynamics and specific solvation. AB - Infrared absorption spectra in the C[triple bond]N stretching frequency region were collected for methyl thiocyanate, the simplest model aliphatic thiocyanate, in several common solvents to establish the dependence of the C[triple bond]N spectral band of aliphatic thiocyanate on its local solvation environment. Systematic changes in the C[triple bond]N bandwidth indicate that it reports on fast solvation dynamics. Anomalous asymmetry and temperature dependence of the C[triple bond]N band in fluorinated alcohol solvents indicates that these solvents participate in formation of a discrete hydrogen-bonded complex with the C[triple bond]N end of methyl thiocyanate. These observations indicate that the C[triple bond]N band of thiocyanate could be an effective site-specific probe of both specific hydrogen bonding and local dynamics in more complex systems, such as peptides and proteins. PMID- 17867663 TI - Synthesis and radioligand binding studies of bis-isoquinolinium derivatives as small conductance Ca(2+)-activated K(+) channel blockers. AB - Starting from the scaffold of N-methyllaudanosine and N-methylnoscapine, which are known small conductance Ca2+-activated K+ channel blockers, original bis isoquinolinium derivatives were synthezised and evaluated using binding studies, electrophysiology, and molecular modeling. These quaternary compounds are powerful blockers, and the most active ones have 10 times more affinity for the channels than dequalinium. The unsubstituted compounds possess a weaker affinity than the analogues having a 6,7-dimethoxy- or a 6,7,8-trimethoxy substitution. The length of the linker has no influence in the alkane derivatives. In relation to the xylene derivatives, the affinities are higher for the ortho and meta isomers. These results are well corroborated by a molecular modeling study. Finally, the most effective compounds have been tested in electrophysiological experiments on midbrain dopaminergic neurons and demonstrate the blocking potential of the apamin-sensitive after-hyperpolarization. PMID- 17867662 TI - 64Cu-Labeled triphenylphosphonium and triphenylarsonium cations as highly tumor selective imaging agents. AB - This report presents synthesis and evaluation of the 64Cu-labeled triphenylphosphonium (TPP) cations as new radiotracers for imaging tumors by positron emission tomography. Biodistribution properties of 64Cu-L1, 64Cu-L2, 64Cu-L3, and 99mTc-Sestamibi were evaluated in athymic nude mice bearing U87MG human glioma xenografts. The most striking difference is that 64Cu-L1, 64Cu-L2, and 64Cu-L3 have much lower heart uptake (<0.6% ID/g) than 99mTc-Sestamibi ( approximately 18% ID/g) at >30 min p.i. Their tumor/heart ratios increase steadily from approximately 1 at 5 min p.i. to approximately 5 at 120 min p.i. The tumor/heart ratio of 64Cu-L3 is approximately 40 times better than that of 99mTc-Sestamibi at 120 min postinjection. Results from in vitro assays show that 64Cu-L1 is able to localize in tumor mitochondria. The tumor is clearly visualized in the tumor-bearing mice administered with 64Cu-L1 as 30 min postinjection. The 64Cu-labeled TPP/TPA cations are very selective radiotracers that are able to provide the information of mitochondrial bioenergetic function in tumors by monitoring mitochondrial potential in a noninvasive fashion. PMID- 17867664 TI - A critical assessment of the performance of protein-ligand scoring functions based on NMR chemical shift perturbations. AB - We have generated docking poses for the FKBP-GPI complex using eight docking programs, and compared their scoring functions with scoring based on NMR chemical shift perturbations (NMRScore). Because the chemical shift perturbation (CSP) is exquisitely sensitive on the orientation of the ligand inside the binding pocket, NMRScore offers an accurate and straightforward approach to score different poses. All scoring functions were inspected by their abilities to highly rank the native-like structures and separate them from decoy poses generated for a protein ligand complex. The overall performance of NMRScore is much better than that of energy-based scoring functions associated with docking programs in both aspects. In summary, we find that the combination of docking programs with NMRScore results in an approach that can robustly determine the binding site structure for a protein-ligand complex, thereby providing a new tool facilitating the structure based drug discovery process. PMID- 17867665 TI - 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines: a series of potent and selective dopamine D(3) receptor antagonists. AB - The discovery of new highly potent and selective dopamine D3 receptor antagonists has recently permitted characterization of the role of the dopamine D3 receptor in a wide range of preclinical animal models. A novel series of 1,2,4-triazol-3 yl-thiopropyl-tetrahydrobenzazepines demonstrating a high level of D3 affinity and selectivity with an excellent pharmacokinetic profile is reported here. In particular, the pyrazolyl derivative 35 showed good oral bioavailability and brain penetration associated with high potency and selectivity in vitro. In vivo characterization of 35 confirmed that this compound blocks the expression of nicotine- and cocaine-conditioned place preference in the rat, prevents nicotine triggered reinstatement of nicotine-seeking behavior in the rat, reduces oral operant alcohol self-administration in the mouse, increases extracellular levels of acetylcholine in the rat medial prefrontal cortex, and potentiates the amplitude of the relative cerebral blood volume response to d-amphetamine in a regionally specific manner in the rat brain. PMID- 17867668 TI - Existing condition and migration property of ions in lithium electrolytes with ionic liquid solvent. AB - Ionization conditions of each ionic species in lithium ionic liquid electrolytes, LiTFSI/BMI-TFSI and LiTFSI/BDMI-TFSI, were confirmed based on the diffusion coefficients of the species measured by the pulsed gradient spin-echo (PGSE) NMR technique. We found that the diffusion coefficient ratios of the cation and anion species D(Li)(obs)/D(F)(obs) of the lithium salt and D(H)(obs)/D(F)(obs) of the ionic liquid solvent were effective guides to evaluate the ionization condition responsible for their mobility. Lithium ions were found to be stabilized, forming the solvated species as Li(TFSI)3(2-). TFSI- anion coordination could be relaxed by the dispersion of silica to form a gel electrolyte, LiTFSI/BDMI-TFSI/silica. It is expected that the oxygen sites on the silica directly attract Li+, releasing the TFSI- coordination. The lithium species, loosing TFSI- anions, kept a random walk feature in the gel without the diffusion restriction attributed from the strong chemical and morphological effect as that in the gel with the polymer. We can conclude that the silica dispersion is a significant approach to provide the appropriate lithium ion condition as a charge-transporting species in the ionic liquid electrolytes. PMID- 17867667 TI - YPED: a web-accessible database system for protein expression analysis. AB - We have developed an integrated web-accessible software system called the Yale Protein Expression Database (YPED) to address the need for storage, retrieval, and integrated analysis of large amounts of data from high throughput proteomic technologies. YPED is an open source system which integrates gel analysis results with protein identifications from DIGE experiments. The system associates the DIGE gel spots and image, analyzed with DeCyder, with mass spectrometric protein identifications from selected gel spots. Following in gel trypsin digestion, proteins in spots of interest are analyzed using MALDI-TOF/TOF on an AB 4700 or, more recently, on an AB 4800 with protein identifications performed by Mascot in conjunction with the AB GPS Explorer system. In addition to DIGE, YPED currently handles protein identifications from MudPIT, iTRAQ, and ICAT experiments. Sample descriptions are compatible with the evolving MIAPE standards. Tandem MS/MS results from MudPIT, and ICAT analyses are validated with the Trans-Proteomic Pipeline and then stored in the database for viewing and linking to the identified proteins. Researchers can view, subset, and download their data through a secure Web interface that includes a table containing proteins identified, a sample summary, the sample description, and a clickable gel image for DIGE samples. Tools are available to facilitate sample comparison and the viewing of phosphoproteins. A summary report with PANTHER Classification System annotations is also available to aid in biological interpretation of the results. The source code is open-source and is available from http://yped.med.yale.edu/yped_dist. PMID- 17867670 TI - Base flipping of the thymine dimer in duplex DNA. AB - Exposure of two adjacent thymines in DNA to UV light of 260-320 nm can result in the formation of the cis,syn-cyclobutane pyrimidine dimer (CPD). The structure of DNA containing an intrahelical CPD lesion has been previously studied experimentally and computationally. However, the structure of the extrahelical, flipped-out, CPD lesion, which has been shown to be the structure that binds to the CPD repair enzyme, DNA photolyase, has yet to be reported. In this work the structure of both the flipped-in and the flipped-out CPD lesions in duplex DNA is reported. These structures were calculated using 8 ns molecular dynamics (MD) simulations. These structures are then used to define the starting and ending points for the base-flipping process for the CPD lesion. Using a complex, two dimensional pseudodihedral coordinate, the potential of mean force (PMF) for the base-flipping process was calculcated using novel methodology. The free energy of the flipped-out CPD is roughly 6.5 kcal/mol higher than that of the flipped-in state, indicating that the barrier to flipping out is much lower for CPD than for undamaged DNA. This may indicate that the flipped-out CPD lesion may be recognized by its repair enzyme, DNA photolyase, whereas previous studies of other damaged, as well as nondamaged, bases indicate that they are recognized by enzymes in the intrahelical, flipped-in state. PMID- 17867669 TI - A theoretical investigation of P-hydroxyphenacyl caged phototrigger compounds: how water induces the photodeprotection and subsequent rearrangement reactions. AB - Complete active-space self-consistent field (CASSCF) calculations with a (14,11) active space and density functional theory calculations followed by Car Parrinello molecular dynamic simulations are reported for the p-hydroxyphenacyl acetate, diethyl phosphate, and diphenyl phosphate phototrigger compounds. These calculations considered the explicit hydrogen bonding of water molecules to the phototrigger compound and help reveal the role of water in promoting the photodeprotection and subsequent rearrangement reactions for the p hydroxyphenacyl caged phototrigger compounds experimentally observed in the presence of appreciable amounts of water but not observed in neat nonproton solvents like acetonitrile. The 267 nm excitation of the phototrigger compounds leads to an instantaneous population of the S3(1pipi*) state Franck-Condon region, which is followed by an internal conversion deactivation route to the S1(1npi*) state via a 1pipi*/1npi* vibronic coupling. The shorter lifetime of the S1(1npi*) state (approximately 1 ps) starting from the FC geometry is terminated by a fast intersystem crossing at a 3pipi*/3npi* intersection with a structure of mixed pipi*/npi* excitation in the triplet state. The deprotection reaction is triggered by a proton (or hydrogen atom) transfer assisted by water bridges and emanates from this pipi*/npi* triplet state intersection. With the departure of the leaving group, the reaction evolves into a water-mediated post-deprotection phase where the spin inversion of pQM (X, 3A) leads to a spiroketone in the ground state by a cyclization process that is followed by an attack of water to produce a 1,1'-di-hydroxyl-spiroketone. Finally, the H atom of the hydroxyl in 1,1'-di-hydroxyl-spiroketon transfers back to the p-O atom aided by water molecules to generate the p-hydroxyphenyl-acetic acid final rearrangement product. PMID- 17867671 TI - Self-organization process of ordered structures in linear and star poly(styrene) poly(isoprene) block copolymers: Gaussian models and mesoscopic parameters of polymeric systems. AB - Mesoscopic simulations of linear and 3-arm star poly(styrene)-poly(isoprene) block copolymers was performed using a representation of the polymeric molecular structures by means of Gaussian models. The systems were represented by a group of spherical beads connected by harmonic springs; each bead corresponds to a segment of the block chain. The quantitative estimation for the bead-bead interaction of each system was calculated using a Flory-Huggins modified thermodynamical model. The Gaussian models together with dissipative particle dynamics (DPD) were employed to explore the self-organization process of ordered structures in these polymeric systems. These mesoscopic simulations for linear and 3-arm star block copolymers predict microphase separation, order-disorder transition, and self-assembly of the ordered structures with specific morphologies such as body-centered-cubic (BCC), hexagonal packed cylinders (HPC), hexagonal perforated layers (HPL), alternating lamellar (LAM), and ordered bicontinuous double diamond (OBDD) phases. The agreement between our simulations and experimental results validate the Gaussian chain models and mesoscopic parameters used for these polymers and allow describing complex macromolecular structures of soft condensed matter with large molecular weight at the statistical segment level. PMID- 17867672 TI - Tautomeric equilibria in phenolic A-ring derivatives of prodigiosin natural products. AB - The prodigiosin natural products contain a common 4-methoxy-pyrromethene chromophore that is attached to a pyrrole A-ring that has its lone-pair nitrogen electrons in conjugation with the pyrromethene entity. This feature is known to play a key role in the biological activities (anticancer, antimicrobial, and immunosuppressive) of the prodigiosins. In an attempt to alter or improve upon the therapeutic potential of the prodigiosins, we have synthesized two new isomeric analogues that contain phenolic A-ring systems (a para (p)-phenol; an ortho (o)-phenol with respect to the pyrromethene) with lone-pair oxygen electrons in conjugation with the pyrromethene chromophore of the natural product. Herein, we report on the optical properties of the phenolic prodigiosin analogues that have been measured using absorbance and steady-state emission spectroscopy. For both analogues absorption measurements in aprotic solvents show that the neutral (L) ligands exist as the enol tautomers with lambda(max) ~ 460 nm, as noted for the parent prodigiosin natural product. However, in polar protic solvents the phenolic derivatives undergo ground-state prototropic tautomerization to generate keto tautomers with lambda(max) ~ 530 nm. This unique feature for a prodigiosin analogue involves proton transfer from the phenolic OH to the pyrromethene N1 proton acceptor atom. Tautomeric equilibrium constants (KT) of 1.4 in 1:4 MeCN/H2O (v/v) have been determined from examination of the absorption spectra. Titration of the o-phenolic derivative with Zn(II) in methanol yielded a 40-fold increase in fluorescence intensity (lambda(max) 542 nm) and generated a new 1:1 complex with Zn(II) with a log K of 5.29, suggesting the potential utility of this analogue to act as a fluorescence probe in a biological matrix to monitor Zn(II) concentrations. Our results demonstrate that phenolic A-ring derivatives of prodigiosins possess some unique properties that may act to enhance the biological properties of the prodigiosin natural products. PMID- 17867673 TI - Ferromagnetic coupling in a 1D coordination polymer containing a symmetric [Cu(mu1,1-N3)2Cu(mu1,1-N3)2Cu]2+ core and based on an organic ligand obtained from the solid state. AB - Addition of rctt-tetrakis(2-pyridyl)cyclobutane (2,2'-tpcb) in a Cu(II)/N(3)- solution afforded the 1D coordination polymer [Cu(3)(N(3))(6)(2,2' tpcb)(DMF)(2)](n) (1). The ligand 2,2'-tpcb serves as a tetradentate bis chelating ligand by linking linear [(DMF)Cu(mu(1,1)-N(3))(2)Cu(N(3))(2)(mu(1,1) N(3))(2)Cu(DMF)] trinuclear units to produce a zigzag chain. Within each centrosymmetric trinuclear unit there exist two irregularly asymmetric end-on double azido-bridged [Cu(mu(1,1)-N(3))(2)Cu](2+) cores, while one of the largest Cu-Nazide-Cu angles is observed. Magnetic susceptibility data, measured from 2 to 300 K, show bulk moderate ferromagnetic coupling within the magnetically isolated trinuclear units. These data were fitted to the appropriate equation derived from the Hamiltonian H = -J(1)(S(A1)S(B) + S(A2)S(B)) - J(2)S(A1)S(A2), giving the parameters J1 = +70(3) cm(-1), J2 = -3(2) cm(-1), g = 2.12(1), with an intertrimer interaction parameter theta = -0.74(2) K. The coupling constants were correlated with the structural parameters. Density functional calculations reproduce very well the experimental J values and show that ferromagnetism for this complex is mainly due to the topology of the magnetic orbitals and the different coordination spheres of two neighboring Cu(II) atoms, resulting in a small overlap of the orbitals possessing the unpaired electrons. PMID- 17867674 TI - Cluster carbonyls of the [Re6(mu3-Se)8]2+ core. AB - The first [Re(6)(mu(3)-Se)(8)](2+) core-containing cluster carbonyls, [Re(6)(mu(3)-Se)(8)(PEt(3))(5)(CO)][SbF(6)](2) and trans-[Re(6)(mu(3) Se)(8)(PEt(3))4(CO)(2)][SbF(6)](2), were produced by reacting [Re(6)(mu(3) Se)(8)(PEt(3))(5)I]I and trans-[Re(6)(mu(3)-Se)8(PEt(3))(4)I2], respectively, with AgSbF(6) in CO-saturated dichloromethane solutions. Spectroscopic and crystallographic studies suggest significant cluster-to-CO back-donation in these novel cluster derivatives and interesting electronic structures. Thermal and photolytic studies of the mono-carbonyl complex revealed its interesting and synthetically useful reactivity in producing new cluster derivatives. PMID- 17867675 TI - Mononuclear Ni(II)-thiolate complexes with pendant thiol and dinuclear Ni(III/II) thiolate complexes with Ni...Ni interaction regulated by the oxidation levels of nickels and the coordinated ligands. AB - Compared to [Ni(II)(SePh)(P(o-C(6)H(3)-3-SiMe(3)-2-S)(2)(o-C(6)H(3)-3-SiMe(3)-2 SH))]- (1a) and [Ni(II)(Cl)(P(o-C(6)H(3)-3-SiMe(3)-2-S)(2)(o-C(6)H(3)-3-SiMe(3)-2 SH))]- (3a) with a combination of the intramolecular [Ni...H-S] and [Ni-S...H-S] interactions, complexes [NiII(SePh)(P(o-C(6)H(3)-3-SiMe(3)-2-S)(2)(o-C(6)H(3)-3 SiMe(3)-2-SH))]- (1b) and [Ni(II)(Cl)(P (o-C(6)H(3)-3-SiMe(3)-2-S)(2)(o-C(6)H(3) 3-SiMe(3)-2-SH))]- (3b) with intramolecular [Ni...H-S] interaction exhibit lower nu(S-H) stretching frequencies (2137 and 2235 cm(-1) for 1b and 3b vs 2250 and 2287 cm(-1) for 1a and 3a, respectively) and smaller torsion angles (27.2 degrees for 3b vs 58.9 and 59.1 degrees for 1a and 3a, respectively). The pendant thiol interaction modes of 1a, 3a, and 3b in the solid state are controlled by the solvent pairs of crystallization. Oxygen oxidation of dinuclear [Ni(II)(P(o C(6)H(3)-3-SiMe(3)-2-S)(2)(o-C(6)H(3)-3-SiMe(3)-2-SH))](2) (4) yielded thermally stable dinuclear [Ni(III)(P(o-C(6)H(3)-3-SiMe(3)-2-S)(2)(o-C(6)H(3)-3-SiMe(3)-2 mu-S))](2) (5). The two paramagnetic d(7) Ni(III) cores (S = 1/2) with antiferromagnetic coupling (J = -3.13 cm(-1)) rationalize the diamagnetic property of 5. The fully delocalized mixed-valence [Ni(II)-Ni(III)] complexes [Ni2(P(o-C(6)H(3)-3-SiMe(3)-2-S)(3))(2)]- (6) and [Ni(2)(P(o-C(6)H(3)-3-SiMe(3)-2 S)(3))(P(o-C(6)H(3)-3-SiMe(3)-2-S)(2)(o-C(6)H(3)-3-SiMe(3)-2-SCH(3)))] (7) were isolated upon the reduction of 5 and the methylation of 6, respectively. The electronic perturbation from the sulfur methylation of 6 triggers the stronger Ni...Ni interaction and the geometrical rearrangement from the diamond shape of the [NiS(2)Ni] core to the butterfly structure of [Ni(mu-S)(2)Ni] to yield 7 with Ni...Ni distances of 2.6088(1) A. The distinctly different Ni...Ni distances (2.6026(7) for 5 and 2.8289(15) A for 6) and the coordination number of the nickels indicate a balance of geometrical requirements for different oxidation levels of [PS(3)Ni-NiPS(3)] cores of 5 and 6. PMID- 17867676 TI - Probing lead(II) bonding environments in 4-substituted pyridine adducts of (2,6 Me2C6H3S)2Pb: an X-ray structural and solid-state 207Pb NMR study. AB - The effect of subtle changes in the sigma-electron donor ability of 4-substituted pyridine ligands on the lead(II) coordination environment of (2,6 Me(2)C(6)H(3)S)(2)Pb (1) adducts has been examined. The reaction of 1 with a series of 4-substituted pyridines in toluene or dichloromethane results in the formation of 1:1 complexes [(2,6-Me(2)C(6)H(3)S)(2)Pb(pyCOH)](2) (3), [(2,6 Me(2)C(6)H(3)S)(2)Pb(pyOMe)](2) (4), and (2,6-Me(2)C(6)H(3)S)(2)Pb(pyNMe(2)) (5) (pyCOH = 4-pyridinecarboxaldehyde; pyOMe = 4-methoxypyridine; pyNMe2 = 4 dimethylaminopyridine), all of which have been structurally characterized by X ray crystallography. The structures of 3 and 4 are dimeric and have psi-trigonal bipyramidal S(3)N bonding environments, with the 4-substituted pyridine nitrogen and bridging sulfur atoms in axial positions and two thiolate sulfur atoms in equatorial sites. Conversely, compound 5 is monomeric and exhibits a psi-trigonal pyramidal S(2)N bonding environment at lead(II). The observed structures may be rationalized in terms of a simple valence bond model and the sigma-electron donor ability of the 4-pyridine ligands as derived from the analysis of proton affinity values. Solid-state (207)Pb NMR experiments are applied in combination with density functional theory (DFT) calculations to provide further insight into the nature of bonding in 4, 5, and (2,6-Me(2)C(6)H(3)S)(2)Pb(py)(2) (2). The lead chemical shielding (CS) tensor parameters of 2, 4, and 5 reveal some of the largest chemical shielding anisotropies (CSA) observed in lead coordination complexes to date. DFT calculations using the Amsterdam Density Functional (ADF) program, which take into account relativistic effects using the zeroth-order regular approximation (ZORA), yield lead CS tensor components and orientations. Paramagnetic contributions to the lead CS tensor from individual pairs of occupied and virtual molecular orbitals (MOs) are examined to gain insight into the origin of the large CSA. The CS tensor is primarily influenced by mixing of the occupied MOs localized on the sulfur and lead atoms with virtual MOs largely comprised of lead 6p orbitals. PMID- 17867678 TI - One-pot synthesis of Schiff-base-containing Ni8 clusters: solvothermal synthesis, structure, and magnetic properties. AB - Solvothermal in situ generation of a Schiff-base ligand (L) in the presence NiCl(2) and trimesic acid (H(3)BTC) in ethanol resulted in clusters, Ni(8)(L)(4)Cl(8).(H(2)O)(0.5), consisting of three different coordination geometries, four paramagnetic and four diamagnetic Ni(II), exhibiting both ferromagnetic and antiferromagnetic exchange interactions. PMID- 17867677 TI - Catalysis design for ring-opening polymerization of cyclic esters: 1. Group 1 metal and thallium(I) trispyrazolylborate complexes with hemilabile ligands. AB - The synthesis of 3-(2-methoxy-1,1-dimethylethyl)pyrazole, pz*H is described together with its reactions with the borohydrides MBH(4), where M = Li, Na, and K, under melt conditions. At 180 degrees C, this procedure leads to a mixture of products for M = Li, and at higher temperatures, a derivative LiTp'pz*H, 1, is isolated, wherein a B-H bond and a methyl group have been eliminated and a B-O bond has been formed. For M = Na, the reaction proceeds to give the tris pyrazolylborate derivative NaTp*, 2, but at higher temperatures the tetra pyrazolylborate complex NaB(pz*)(4), 3, is obtained. The reactions involving KBH4 and pz*H yield the dinuclear complex K(2)(Tp*)(2)pz*H, 4. The reaction between NaTp* and TlOAc in CH(2)Cl(2) at room temperature leads to the formation of TlTp*, 5, along with NaOAc. Thallium 5 reacts with methyllithium in diethylether to give LiTp*, 6, and thallium metal, and, similarly, 5 and KH react in tetrahydrofuran to give KTp*, 7 and Tl(0). 1-7 have been characterized by elemental analysis, NMR spectroscopy, and by single-crystal X-ray studies, the latter of which reveal the versatile modes of binding for this new ligand bearing hemilabile ether appendages. PMID- 17867679 TI - Luminescent charge-transfer platinum(II) metallacycle. AB - The photophysical and electrochemical properties of a platinum(II) diimine complex bearing the bidentate diacetylide ligand tolan-2,2'-diacetylide (tda), Pt(dbbpy)(tda) [dbbpy = 4,4'-di-tert-butyl-2,2'-bipyridine] (1), are compared with two reference compounds, Pt(dbbpy)(C[triple bond]CPh)(2) (2) and Pt(dppp)tda [dppp = 1,3-bis(diphenylphosphino)propane] (3), respectively. The X-ray crystal structure of 1 is reported, which illustrates the nearly perfect square planarity exhibited by this metallacycle. Chromophore 2 possesses low-lying charge-transfer excited states analogous to 1, whereas structure 3 lacks such excited states but features a low-lying platinum-perturbed tda intraligand triplet manifold. In CH(2)Cl(2), 1 exhibits a broad emission centered at 562 nm at ambient temperature, similar to 2, but with a higher photoluminescence quantum yield and longer excited-state lifetime. In both instances, the photoluminescence is consistent with triplet-charge-transfer excited-state parentage. The rigidity imposed by the cyclic diacetylide ligand in 1 leads to a reduction in nonradiative decay, which enhances its room-temperature photophysical properties. By comparison, 3 radiates highly structured tda-localized triplet-state phosphorescence at room temperature. The 77 K emission spectrum of 1 in 4:1 EtOH/MeOH becomes structured and is quantitatively similar to that measured for 3 under the same conditions. Because the 77 K spectra are nearly identical, the emissions are assigned as (3)tda in nature, implying that the charge-transfer states are raised in energy, relative to the (3)tda levels in 1 in the low temperature glass. Nanosecond transient absorption spectrometry and ultrafast difference spectra were determined for 1-3 in CH(2)Cl(2) and DMF at ambient temperature. In 1 and 2, the major absorption transients are consistent with the one-electron reduced complexes, corroborated by reductive spectroelectrochemical measurements performed at room temperature. As 3 does not possess any charge transfer character, excitation into the pipi* transitions of the tda ligand generated transient absorptions in the relaxed excited state assigned to the ligand-localized triplet state. In all three cases, the excited-state lifetimes measured by transient absorption are similar to those measured by time-resolved photoluminescence, suggesting that the same excited states giving rise to the photoluminescence are responsible for the absorption transients. ESR spectroscopy of the anions 1- and 2- and reductive spectroelectrochemistry of 1 and 2 revealed a LUMO based largely on the pi* orbital of the dbbpy ligand. Time-dependent density functional theory calculations performed on 1-3 both in vacuum and in a CH(2)Cl(2) continuum revealed the molecular orbitals, energies, dipole moments, and oscillator strengths for the various electronic transitions in these molecules. A DeltaSCF-method-derived shift applied to the calculated transition energies in the solvent continuum yielded good agreement between theory and experiment for each molecule in this study. PMID- 17867680 TI - Synthesis and characterization of diorganohydrazido(2-) tungsten complexes. AB - Diorganohydrazido(2-) complexes of tungsten (L)Cl4W(NNR2) [R2=Me2, Ph2, -(CH2)5-; L=CH3CN, pyridine] were synthesized by reacting the corresponding 1,1 diorganohydrazine with WCl6, followed by reaction with acetonitrile or pyridine. Crystallographic structure determination of (CH3CN)Cl4W(NNMe2) and (CH3CN)Cl4W(NNPh2) allows a comparison of the structural features of the diorganohydrazido(2-) functionality with varying substituents. Mass spectrometry, thermogravimetric analysis, and preliminary chemical vapor deposition experiments were performed to determine the viability of these complexes as single-source precursors for deposition of WNx and WNxCy films. PMID- 17867681 TI - Formation of a phosphine-phosphinite ligand in RhCl(PRR'2)[P,P R'(R)POCH2P(CH2OH)2] and R'H from cis-RhCl(PRR'2)2[P(CH2OH)3] via P-C bond cleavage. AB - Reaction of RhCl(1,5-cod)(THP), where THP = P(CH(2)OH)(3), with several PRR'2 phosphines (R = or not equal R') generates, concomitantly with R'H, the derivatives RhCl(PRR'(2))[P,P-R'(R)POCH(2)P(CH(2)OH)(2)] in two isomeric forms. The hydrogen of the hydrocarbon co-product derives from a THP hydroxyl group which becomes an 'alkoxy' group at the residual PRR' moiety, this resulting in the P,P-chelated R'(R)POCH(2)P(CH(2)OH)(2) ligand. One of the isomers of the PPh(3) system, cis-RhCl(PPh(3))[P,P-P(Ph)(2)OCH(2)P(CH(2)OH)(2)], was structurally characterized (cis refers to the disposition of the P atoms with Ph substituents). PMID- 17867682 TI - Reactivity and mechanism of stable heterocyclic silylenes with carbon tetrachloride. AB - The potential energy surfaces for the reactions of stable silylenes with carbon tetrachloride have been characterized in detail using density functional theory [B3LYP/6-311G(d)], including zero-point corrections. Five stable silylene species (1-5) have been chosen in this work as model reactants. The activation barriers and enthalpies of the reactions are compared to determine the relative reactivity of the stable silylenes on the reaction potential energy surface. Our theoretical findings suggest that stable silylene 5, which has two carbon atoms bonded to the silicon center and does not contain a resonance structure, is relatively unstable with respect to the reaction with haloalkanes, in comparison with the other stable silylenes (1-4). Of the three possible reaction paths, Cl abstraction (path 1), CCl3 abstraction (path 2), and CCl4 insertion (path 3), path 1 is found to be most favorable, with a very low activation energy and a large exothermicity. In short, electronic as well as steric factors play a dominant role in determining the chemical reactivity of the stable silylene species kinetically as well as thermodynamically. Furthermore, a configuration mixing model based on the work of Pross and Shaik is used to rationalize the computational results. The results obtained allow a number of predictions to be made. PMID- 17867684 TI - A thallium mediated route to sigma-arylalkynyl complexes of bipyridyltricarbonylrhenium(I). AB - A simple, one-pot preparation of rhenium(I) sigma-arylalkynyl complexes is reported using thallium(I) hexafluorophosphate as a halogen abstraction agent. This new route to rhenium sigma-alkynyls enjoys higher yields compared to analogous preparations using silver salts by eliminating potential electrochemical degradation pathways. PMID- 17867683 TI - Synthesis, photophysical, and anion-sensing properties of quinoxalinebis(sulfonamide) functionalized receptors and their metal complexes. AB - We report the synthesis, characterization, and photophysical properties of a series of organic receptors and their corresponding ReI and RuII metal complexes as anion probes featuring bis(sulfonamide) interacting sites incorporating highly chromophoric pi-conjugated quinoxaline moieties. The interactions with various anions were extensively investigated. These probe molecules are capable of recognizing F-, OAc-, CN-, and H2PO4- with different sensitivities. The probe anion interactions can be easily visualized via naked-eye colorimetric or luminescent responses. Probe 1 has the weakest acidic sulfonamide N-H protons and therefore simply forms hydrogen-bonding complexes with F-, OAc-, CN-, and H2PO4-. Probe 2 undergoes a stepwise process with the addition of F- and OAc-: formation of a hydrogen-bound complex followed by sulfonamide N-H deprotonation. Direct sulfonamide N-H deprotonation occurs upon the addition of CN-, while only a hydrogen-bound complex forms with the H2PO4- ion for probe 2 in a dimethyl sulfoxide (DMSO) solution. Similar probe-anion interactions occur in probe 3 with the addition of F-, CN-, or H2PO4-. However, only a genuine hydrogen-bound complex forms in the presence of the OAc- ion in a DMSO solution of probe 3 because of the subtle difference in the pKa values of sulfonamide N-H protons when probes 2 and 3 are compared. Coordination of probe 1 to a ReI center or probe 2 to a RuII center increases the intrinsic acidity of sulfonamide N-H protons and results in an enhanced sensitivity to anions. PMID- 17867685 TI - Novel coordination polymers based on the tetrathioterephthalate dianion as the bridging ligand. AB - The first examples of coordination polymers based on the tetrathioterephthalate dianion as the bridging ligand are reported. Two novel compounds, [M(S(2)CC(6)H(4)CS(2))(DMF)(2)](DMF) (M = Zn, Mn; DMF = dimethylformamide), have been synthesized, and their structural and optical properties were investigated. PMID- 17867687 TI - Functionalization of zeolitic cavities: grafting NH2 groups in framework T sites of B-SSZ-13--a way to obtain basic solids catalysts? AB - Insertion of B atoms into an Al-free zeolitic framework with CHA topology results in the formation of B-SSZ-13 zeotype with Si/B = 11. B K-edge NEXAFS testifies that B forms [B(OSi)4] units in a Td-like geometry (sp3-hybridized B atoms). According to B K-edge NEXAFS and IR, template burning results in the formation of [B(OSi)3] units in a D3h-like geometry (sp2-hybridized B atoms) with a break of a B-O-Si bond and the formation of a Si-OH group. The activated material contains B(III) Lewis acid centers able to specifically coordinate bases like NH3. Such [B(OSi)3] units are reactive toward ammonia, resulting in the formation of B-NH2 surface functionality inside the pores of B-SSZ-13 already under mild conditions, i.e., 35 mbar of NH3 at 373 K for 30 min and without crystallinity degradation. A minor fraction of Si-NH2 cannot be excluded owing to the presence of two IR doublets at 3500 and 3430 cm-1 and at 1600 and 1550 cm-1. Ab initio B3LYP/6 31+G(d,p) calculations on a cluster model, supported by a single-point MP2 on B3LYP/6-31+G(D,P) optimized structures, found the break by NH3 of a B-O-Si bond of the [B(OSi)3] unit with formation of [SiOH] and [H2N-B(OSi)2] species to be energetically favored. Comparison between experimental and computed frequency shifts shows them to be in semiquantitative agreement. The high stability of the B-NH2 surface functionality is probed by N K-edge NEXAFS spectra collected under UHV conditions. These findings can open a new route in the preparation of shape selective solid basic catalysts. PMID- 17867686 TI - Periodic trends within a series of five-coordinate thiolate-ligated [MII(SMe2N4(tren))]+ (M = Mn, Fe, Co, Ni, Cu, Zn) complexes, including a rare example of a stable CuII-thiolate. AB - A series of five-coordinate thiolate-ligated complexes [M(II)(tren)N4S(Me2)]+ (M = Mn, Fe, Co, Ni, Cu, Zn; tren = tris(2-aminoethyl)amine) are reported, and their structural, electronic, and magnetic properties are compared. Isolation of dimeric [Ni(II)(SN4(tren)-RS(dang))]2 ("dang"= dangling, uncoordinated thiolate supported by H bonds), using the less bulky [(tren)N4S](1-) ligand, pointed to the need for gem-dimethyls adjacent to the sulfur to sterically prevent dimerization. All of the gem-dimethyl derivatized complexes are monomeric and, with the exception of [Ni(II)(S(Me2)N4(tren)]+, are isostructural and adopt a tetragonally distorted trigonal bipyramidal geometry favored by ligand constraints. The nickel complex uniquely adopts an approximately ideal square pyramidal geometry and resembles the active site of Ni-superoxide dismutase (Ni SOD). Even in coordinating solvents such as MeCN, only five-coordinate structures are observed. The MII-S thiolate bonds systematically decrease in length across the series (Mn-S > Fe-S > Co-S > Ni-S approximately Cu-S < Zn-S) with exceptions occurring upon the occupation of sigma* orbitals. The copper complex, [Cu(II)(S(Me2)N4(tren)]+, represents a rare example of a stable CuII-thiolate, and models the perturbed "green" copper site of nitrite reductase. In contrast to the intensely colored, low-spin Fe(III)-thiolates, the M(II)-thiolates described herein are colorless to moderately colored and high-spin (in cases where more than one spin-state is possible), reflecting the poorer energy match between the metal d- and sulfur orbitals upon reduction of the metal ion. As the d-orbitals drop in energy proceeding across the across the series M(2+) (M= Mn, Fe, Co, Ni, Cu), the sulfur-to-metal charge-transfer transition moves into the visible region, and the redox potentials cathodically shift. The reduced M(+1) oxidation state is only accessible with copper, and the more oxidized M(+4) oxidation state is only accessible for manganese. PMID- 17867688 TI - Magnetic assembly and patterning of vesicle/nanoparticle aggregates. PMID- 17867690 TI - Hexabenzo[4.4.4]propellane: a helical molecular platform for the construction of electroactive materials. AB - Helical hexabenzo[4.4.4]propellane (a relative of hexaphenylethane) and its derivatives are synthesized and their structures are established by X-ray crystallography. Isolation and X-ray crystallographic characterization of a robust trication-radical salt of hexamethoxypropellane derivative confirms that its framework is stable toward oxidative (aliphatic) C-C bond cleavage. It is also demonstrated that propellane can be easily brominated at the 4,4'-positions of the biphenyl linkages for its usage as a molecular platform for the preparation of electroactive materials. PMID- 17867689 TI - Probing the thermodynamics of aminofluorene-induced translesion DNA synthesis by differential scanning calorimetry. PMID- 17867691 TI - Enantioselective formal [3+3] annulation for the direct construction of bicyclic skeletons with four stereogenic centers. AB - An enantioselective formal [3+3] annulation reaction of cyclic ketones with enones has been developed. In the presence of 20 mol % of pyrrolidine-thiourea 1a or N-(pyrrolidin-2-ylmethyl)trifluoromethanesulfonamide 1i, the reactions afford bicyclo [3.3.1] adducts in moderate to good yields with good to high enantioselectivities under mild conditions. PMID- 17867692 TI - Self-assembly of okadaic acid as a pathway to the cell. AB - The polyether toxin okadaic acid (OA) inhibits several protein serine/threonine phosphatases that play central roles in the regulation of many essential cellular processes. The use of scanning tunneling microscopy (STM) shows that dimerization of such toxins is crucial to understand the mechanism of toxin transport across model membranes. PMID- 17867693 TI - Enol esters: versatile substrates for Mannich-type multicomponent reactions. AB - The interaction of cyclic enol esters with diversely substituted anilines and ethyl glyoxalate yields, under Sc(OTf)3 catalysis, disubstituted N-aryl lactams in a multicomponent reaction. The protocol allows access to the trans stereoisomers after an epimerization of the initial mixture in which the cis isomers predominate. Vinyl acetate yields quinoline derivatives, whereas isopropenyl acetate leads to the corresponding Mannich adducts. PMID- 17867694 TI - Convenient synthesis of highly functionalized pyrazolines via mild, photoactivated 1,3-dipolar cycloaddition. AB - A mild, photoactivated 1,3-dipolar cycloaddition procedure was successfully developed for the synthesis of polysubstituted pyrazolines. This procedure involved the in situ generation of the reactive nitrile imine dipoles using a hand-held UV lamp at 302 nm, followed by spontaneous cycloaddition with a broad range of 1,3-dipolarophiles with excellent solvent compatibility, functional group tolerance, regioselectivity, and yield. PMID- 17867695 TI - Divergent synthesis of cytotoxic styryl lactones from D-xylose. The first total synthesis of (+)-crassalactone C. AB - A new divergent approach to (+)-goniofufurone (1) and 7-epi-(+)-goniofufurone (2), as well as the first total synthesis of crassalactone C (3), has been achieved starting from D-xylose. In a preliminary bioassay, all three natural products 1, 2, and 3 showed remarkable in vitro antiproliferative activities against K562, Raji, and HeLa neoplastic cell lines. PMID- 17867696 TI - Cascade coupling/cyclization process to N-substituted 1,3-dihydrobenzimidazol-2 ones. AB - Assembly of N-substituted 1,3-dihydrobenzimidazol-2-ones is achieved starting from methyl o-haloarylcarbamates via a CuI/amino acid catalyzed coupling with amines and subsequent condensative cyclization. A number of functional groups are tolerated by these reaction conditions, including vinyl, nitro, carboxylate, amide, ester, ketone, and silyl ether groups. PMID- 17867697 TI - Palladium(II)-catalyzed annulation of alkynes with ortho-ester-containing phenylboronic acids. AB - Palladium(II) catalyzes annulation of internal alkynes with methyl 2 boronobenzoate and (2-boronophenyl)acetate to provide 2,3-disubstituted indenones and 3,4-disubstituted 2-naphthols, respectively. The annulation reaction would proceed through transmetalation of Pd(II) with the boron reagents and insertion of the alkynes, followed by unprecedented 1,2-addition of the generated alkenylpalladium(II) species to the intramolecular ester group. PMID- 17867698 TI - Enantio- and diastereoselective synthesis of syn-beta-hydroxyallylsilanes via a chiral (Z)-gamma-silylallylboronate. AB - syn-beta-Hydroxyallylsilanes of general structure 11 and 28 are prepared in 50 86% yield and 91-95% ee (for aliphatic aldehydes; 50% ee for benzaldehyde) via the BF(3).Et(2)O-promoted gamma-silylallylboration reactions, using reagents 14 and 15. PMID- 17867699 TI - A nonacid degradable linker for solid-phase synthesis. AB - Synthesis and applications of two new nonacid degradable linkers as an alternative to the Wang linker for solid-phase synthesis are described. Resin from linker 2 looks superior to linker 1 in terms of yields for both anchoring of the first building block and cleavage and in terms of higher purity of the final product. Use of linker 2 avoids side reactions associated with the use of Wang resin due to an undesired cleavage during final acid treatment. PMID- 17867700 TI - Diastereoselective intermolecular cobalt-catalyzed reductive aldol reactions of alpha,beta-unsaturated amides with ketones. AB - Under cobalt catalysis, diethylzinc mediates the conjugate reduction of alpha,beta-unsaturated amides to produce ethylzinc enolates that react with ketones in situ to produce tertiary alcohol-containing aldol products with up to >19:1 diastereoselectivity. PMID- 17867701 TI - Electrocatalytic formal [2+2] cycloaddition reactions between anodically activated enyloxy benzene and alkenes. AB - Electrocatalytic formal [2+2] cycloadditions between anodically activated enyloxy benzene and alkenes have been accomplished in a lithium perchlorate/nitromethane electrolyte solution. The enyloxy benzene moiety of these electrolytic substrates played an important role in the formation of a radical cation that could accept nucleophilic alkenes, followed by intramolecular electron transfer between the cyclobutane and phenyl ether moieties of the intermediates. PMID- 17867702 TI - Copper(I)-catalyzed highly efficient synthesis of benzoselenazoles and benzotellurazoles. AB - A simple and practical useful synthetic method of 1,3-benzoselenazoles having a heteroatom substituent such as NRR', OR, and SR groups at the 2-position was developed by the copper(I)-catalyzed reaction of 2-bromophenyl (1) or 2 iodophenyl (2) isocyanides with selenium and heteroatom nucleophiles. In addition, the synthesis of 2-amino-1,3-benzotellurazoles is also described. PMID- 17867703 TI - Stereocontrolled access to orthogonally protected anti,anti-4-aminopiperidine-3,5 diols through chemoselective reduction of enantiopure beta-lactam cyanohydrins. AB - The cyanosilylation of enantiopure 4-oxoazetidine-2-carbaldehydes with tert butyldimethylsilyl cyanide was promoted by either molecular sieves or catalytic amount of sodium carbonate to give O-silylated beta-lactam cyanohydrins with good yield and diastereoselectivity. In contrast, Lewis acids did not effectively promote the cyanosilylation under different experimental conditions, and instead hydrocyanation took place affording the corresponding free cyanohydrins in variable yield and selectivity. Starting from beta-lactam cyanohydrin hybrids, two concise, complementary stereocontrolled routes to optically pure orthogonally protected anti,anti-4-amino-3,5-piperidine diols were achieved. Key features of the first approach include chemoselective reductive opening of the beta-lactam ring with LiBH4 to a 3-amino-5-hydroxy pentanenitrile followed by reductive cyclization of a conveniently functionalized cyanomesylate derivative with NaBH4/NiCl2. The second approach involves LiAlH4 reduction of protected anti,anti 4-amino-3,5-dihydroxypiperidin-2-ones, which were easily obtained by chemoselective reduction of the cyano group in the beta-lactam cyanohydrin hybrids with NaBH4/NiCl2 and subsequent intramolecular rearrangement of the resulting amino beta-lactams. Both routes make use of an oxidative N-dearylation with diacetoxyiodobenzene of a 4-methoxyphenylamino group as a common synthetic step. Specifically, the utility of this novel reaction sequence has been demonstrated by the synthesis of fully orthogonally protected sialidase inhibitors. PMID- 17867704 TI - Synthesis of methyl 1-hydroxy-6-oxo-2-cyclohexenecarboxylate, a component of salicortin and tremulacin, and the monomer of idesolide. AB - We have developed a short and practical first synthesis of methyl 1-hydroxy-6-oxo 2-cyclohexenecarboxylate (2), which has been known as a component of salicortin and tremulacin since 1970. Birch reduction of the SEM ether of methyl salicylate followed by oxidation of the intermediate enolate with (-) camphorsulfonyloxaziridine afforded the SEM enol ether of 2. Hydrolysis of the SEM enol ether afforded 2. We did not observe the dimerization of either racemic or optically enriched 2 to give idesolide (1). PMID- 17867705 TI - Aza-Prins-pinacol approach to 7-azabicyclo[2.2.1]heptanes: syntheses of (+/-) epibatidine and (+/-)-epiboxidine. AB - The syntheses of (+/-)-epibatidine and (+/-)-epiboxidine have been accomplished from commercial 2-methoxy-3,4-dihydro-2H-pyran. A recently developed aza-Prins pinacol rearrangement was employed for the construction of the key 7 azabicyclo[2.2.1]heptane skeleton of these targets. PMID- 17867706 TI - Isolation and characterization of okadaic acid binding proteins from the marine sponge Halichondria okadai. AB - Okadaic acid, first isolated from the marine sponge Halichondria okadai, is a potent inhibitor of protein phosphatases 1 and 2A (PP1 and PP2A, respectively). Photoaffinity labeling experiments previously performed with biotinylated photoreactive okadaic acid revealed the presence of okadaic acid binding protein (OABP) in the crude extract of H. okadai. In this article, OABP1 and OABP2 were purified from H. okadai as guided by the binding affinity of [27-3H]okadaic acid. OABP1 has an approximate molecular mass of 37 kDa in SDS-PAGE analysis. Edman degradation followed by molecular cloning and sequencing identified OABP1 as being 88% identical to the rabbit PP2Abeta catalytic subunit. On the other hand, HPLC analysis revealed that OABP2 consists of three 22 kDa proteins (OABP2.1, OABP2.2, and OABP2.3). Electrospray ionization mass spectrometry indicated that OABP2.1 and OABP2.2 form a complex with okadaic acid. The complete amino acid sequence of OABP2, determined by Edman degradation and molecular cloning, showed that OABP2.1 is 96% identical to OABP2.2 and 66% identical to OABP2.3, while being very slightly homologous to any protein phosphatases known to date. OABP2 did not exhibit phosphatase activity, though it bound to okadaic acid with a Kd of 0.97 nM. Furthermore, OABP2 was not detected in the sponge Halichondria japonica or the dinoflagellate Prorocentrum lima. We thus speculated that OABP2 might be involved in detoxifying okadaic acid. PMID- 17867708 TI - Use of Lawesson's reagent in organic syntheses. PMID- 17867707 TI - An aminoglycoside microarray platform for directly monitoring and studying antibiotic resistance. AB - Antibiotic resistance is a major threat to human health. Since resistance to the aminoglycoside class of antibiotics is most commonly caused by enzymatic modification, we developed a high-throughput microarray platform for directly assaying resistance enzyme activity on aminoglycosides. After modification, the array can be hybridized with the therapeutic target, a bacterial rRNA A-site mimic, to study the effect that modification has on binding. Such studies will help identify important factors that contribute to high-affinity recognition of therapeutic targets and low-affinity recognition of and modification by resistance enzymes. This platform may also be useful for screening chemical libraries to discover new antibiotics that evade resistance. PMID- 17867710 TI - Dielectrophoretic levitation in the presence of shear flow: implications for colloidal fouling of filtration membranes. AB - The ability of dielectrophoretic (DEP) forces created using a microelectrode array to levitate particles in a colloidal suspension is studied experimentally and theoretically. The experimental system employs microfabricated electrode arrays on a glass substrate to apply repulsive DEP forces on polystyrene latex particles suspended in an aqueous medium. A numerical model based on the convection-diffusion-migration equation is presented to calculate the concentration distribution of colloidal particles in shear flow under the influence of a repulsive DEP force field. The results obtained from the numerical simulations are compared against trajectory analysis results and experimental data. The results indicate that by incorporating ac electric field-induced DEP forces in a shear flow, particle accumulation and deposition on the flow channel surfaces can be significantly reduced or even completely averted. The mathematical model is then used to indicate how the deposition behavior is modified in the presence of a permeable substrate, representative of tangential flow membrane filtration operations. The results indicate that the repulsive dielectrophoretic (DEP) forces imparted to the particles suspended in the feed can be employed to mitigate membrane fouling in a cross-flow filtration process. PMID- 17867709 TI - Computational modeling of poly(alkylthiophene) conductive polymer insertion into phospholipid bilayers. AB - We have previously demonstrated that some poly(alkylthiophenes) (PATs) are able to increase the electrical conductance of unsupported phospholipid bilayers and have hypothesized that this effect is due to the ability of some PAT side chains to permit stable insertion into the bilayer. We have further proposed the development of long-term intracellular electrodes based on that phenomenon. In this article, we apply molecular dynamics techniques to study the insertion of two model PATs into a patch of a lipid bilayer. Steered molecular dynamics is used to obtain potential trajectories of insertion, followed by umbrella sampling to determine the free-energy change upon insertion. Our results indicate that both branched-side-chain poly(3-(2-ethylhexyl)thiophene) (EHPT) and straight-side chain poly(3-hexylthiophene) (HPT) are able to enter the bilayer but only EHPT can cross the center of the membrane and establish an electrical bridge. HPT penetrates the head groups but is not able to enter the alkyl tail phase. These findings support the feasibility of our electrode concept and raise questions regarding the mechanisms by which branched side chains grant PATs greater solubility in a lipid bilayer environment. The parameters and methods used in this study establish a novel framework for studying these and similar systems, and the results hold promise for the use of EHPT in biosensing and neural interfacing. PMID- 17867711 TI - Reversible helix sense inversion in surface-grafted poly(beta-phenethyl-L aspartate) films. AB - The reversible manipulation of the helix screw sense in surface-grafted poly(beta phenethyl-L-aspartate) (PPELA) films by means of external stimuli was investigated. Ringopening polymerization of beta-phenethyl-L-aspartate N carboxyanhydride initiated from primary amino-functionalized silicon and quartz substrates results in surface-grafted PPELA films in which the end-grafted polypeptide chains have a right-handed alpha-helical conformation. Upon annealing of the film at 150 degrees C for 30 min, a helix screw sense inversion takes place and the grafted chains adopt a left-handed pi-helical conformation. In the solid state, this left-handed pi-helical form is completely stable and cannot be changed by reheating and/or cooling. Upon immersion of the annealed grafted film in chloroform or other helicogenic solvents, the grafted polypeptide chains completely revert to their original right-handed alpha-helical form. Successive annealing and solvent treatment steps show that this helix sense inversion cycle can be repeated many times. PMID- 17867712 TI - A small angle neutron scattering study of the adsorbed asphaltene layer in water in-hydrocarbon emulsions: structural description related to stability. AB - We have developed a specific protocol to study with SANS measurements, the structure of the interfacial film layer in water-in-oil emulsions stabilized by asphaltene. Using the contrast matching technique available for neutron scattering, we have access to both the composition and the quantity of interface. The results obtained give us a view of the asphaltene aggregates in the interfacial film, which are structured as a monolayer and show a direct correlation between the size of asphaltene aggregates in solution and the thickness of the film layer. The organization of the interface has been studied as a function of several parameters such as the quantity of resins, i.e., the size of aggregates, the pH of the aqueous phase, and the aging time of the emulsions and the consequences of these variations on the macroscopic stability of these emulsions. We show that the key parameter for the stability is the inter asphaltene aggregate interaction inside the film layer. Changing the attractive/repulsive balance between the aggregates in the film at the microscopic scale, by changing the aggregate's size or the aggregate's ionization, has a direct incidence on the quantity of water recovered after centrifugation: the stronger the attraction between aggregates in the film, the more stable the emulsion is. PMID- 17867713 TI - Experimental investigation of the link between static and dynamic wetting by forced wetting of nylon filament. AB - Forced wetting experiments with various liquids were conducted to study the dynamic wetting properties of nylon filament. The molecular-kinetic theory of wetting (MKT) was used to interpret the dynamic contact angle data and evaluate the contact-line friction zeta0 at the microscopic scale. By taking account of the viscosity of the liquid, zeta0 could be related exponentially to the reversible work of adhesion. This clearly establishes an experimental link between the static and dynamic wetting properties of the material. Moreover, statistical analysis of the equilibrium molecular displacement frequency K0 and the length of the displacements lambda reveals that these two fundamental parameters of the MKT are strongly correlated, not only in the linearized form of the theory (valid close to equilibrium) but also when the nonlinear form of the equations has to be considered at higher wetting speeds. PMID- 17867714 TI - Shear-induced topology changes in liquid crystals of the soybean lecithin/DDAB/water system. AB - The viscoelastic behavior of the two different liquid crystalline lamellar phases and the liquid crystalline cubic phase of the mixed soybean lecithin/DDAB system in water was studied through rheology, with mechanical parameters studied as a function of composition. The swollen or diluted lamellar region is formed by vesicles, and its characteristic flow curve presents two-power law regions separated by a region where viscosity passes through a maximum. Yield stress and shear-dependent flow behavior were also observed. The microstructure suffers transformation under shear stress, and rheological response shifts from thixotropic to antithixotropic loops. Similar rheological behavior has been observed for samples in the collapsed or concentrated lamellar region, at the water-rich corner of the phase diagram. Vesicle formation may therefore occur by shearing the initial stacked and open bilayers. However, concentrated lamellar samples in the water-poor part of the phase diagram are less sensitive to shear effects and show plastic behavior and thixotropy. All lamellar samples manifest high elasticity. The dynamic responses of both lamellar topologies, i.e., vesicles and open bilayers, are comparable and exhibit an infinite relation time. The bicontinuous cubic, liquid crystalline phase is highly viscous. Its dynamic response cannot be modeled by a Maxwell model. PMID- 17867715 TI - Synthesis, characterization, and self-assembly of protein lysozyme monolayer stabilized gold nanoparticles. AB - Lysozyme monolayer-protected gold nanoparticles (Au NPs) which are hydrophilic and biocompatible and show excellent colloidal stability (at low temperature, ca. 4 degrees C), were synthesized in aqueous medium by chemical reduction of HAuCl4 with NaBH4 in the presence of a familiar small enzyme, lysozyme. UV-vis spectra, transmission electron microscopy (TEM), atomic force microscopy, and X-ray photoelectron spectroscopy characterization of the as-prepared nanoparticles revealed the formation of well-dispersed Au NPs of ca. 2 nm diameter. Moreover, the color change of the Au NP solution as well as UV-vis spectroscopy and TEM measurements have also demonstrated the occurrence of Ostwald ripening of the nanoparticles at low temperature. Further characterization with Fourier transform infrared spectroscopy (FTIR) and dynamic light scattering indicated the formation of a monolayer of lysozyme molecules on the particle surface. FTIR data also indicated the intactness of the protein molecules coated on Au NPs. All the characterization results showed that the monodisperse Au NPs are well-coated directly with lysozyme. Driven by the dipole-dipole attraction, the protein stabilized Au NPs self-assembled into network structures and nanowires upon aging under ambient temperature. On the basis of their excellent colloidal stability, controlled self-assembly ability, and biocompatible surface, the lysozyme monolayer-stabilized Au NPs hold great promise for being used in nanoscience and biomedical applications. PMID- 17867716 TI - Toward the extraction of single species of single-walled carbon nanotubes using fluorene-based polymers. AB - High purity of (7,5) SWNTs (approximately 79% of the semisonducting SWNT ensemble) can be obtained by polymer-assisted extraction from the narrow-diameter distributed SWNTs produced by the catalyst Co-MCM-41. The fluorene-based polymers are able to selectively wrap the single-walled carbon nanotubes (SWNTs) with certain chiral angles or diameters depending on their chemical structures. Poly(9,9-dioctyfluoreny1-2, 7-diyl) and poly[(9,9-dihexylfluorenyl-2,7-diyl)-co (9,10-anthracene)] selectively wrap SWNTs with high chiral angles (>24.5 degrees). By contrast, poly[9,9-dioctylfluorenyl-2,7-diyl)-co-1,4-benzo-{2,1'-3} thiadiazole)] preferentially wraps the SWNTs with certain diameter (1.02-1.06 nm). PMID- 17867717 TI - s-Electron ferromagnetism in gold and silver nanoclusters. AB - Ferromagnetic (FM) ordering in transition-metal systems (solids, surface layers, nanoparticles) arises from partially filled d shells. Thus, recent observations of FM Au nanoclusters was unexpected, and an explanation has remained elusive. Here we report first-principles density-functional spin-polarized calculations for Au and Ag nanoclusters. We find that the highest-occupied level is highly degenerate and partially filled by s electrons with spins aligned according to Hund's rule. The nanoclusters behave like "superatoms", with the spin-aligned electrons being itinerant on the outer shell of atoms. PMID- 17867718 TI - InAs/InP radial nanowire heterostructures as high electron mobility devices. AB - Radial core/shell nanowires (NWs) represent an important class of one-dimensional (1D) systems with substantial potential for exploring fundamental materials electronic and photonic properties. Here, we report the rational design and synthesis of InAs/InP core/shell NW heterostructures with quantum-confined, high mobility electron carriers. Transmission electron microscopy studies revealed single-crystal InAs cores with epitaxial InP shells 2-3 nm in thickness, and energy-dispersive X-ray spectroscopy analysis further confirmed the composition of the designed heterostructure. Room-temperature electrical measurements on InAs/InP NW field-effect transistors (NWFETs) showed significant improvement in the on-current and transconductance compared to InAs NWFETs fabricated in parallel, with a room-temperature electron mobility, 11,500 cm(2)/Vs, substantially higher than other synthesized 1D nanostructures. In addition, NWFET devices configured with integral high dielectric constant gate oxide and top-gate structure yielded scaled on-currents up to 3.2 mA/microm, which are larger than values reported for other n-channel FETs. The design and realization of high electron mobility InAs/InP NWs extends our toolbox of nanoscale building blocks and opens up opportunities for fundamental and applied studies of quantum coherent transport and high-speed, low-power nanoelectronic circuits. PMID- 17867719 TI - AuthorChoice: a great way to get your papers read. PMID- 17867720 TI - The need for definitions in pharmacovigilance. PMID- 17867721 TI - A case study of a graphical misrepresentation: drawing the wrong conclusions about the measles, mumps and rubella virus vaccine. AB - Graphs have been used in attempts to show a relationship between the measles, mumps and rubella virus (MMR) vaccine and autism. We examine the topic of graphical representation of data in general, and one of these graphs in particular: the one that appeared in a 1999 letter to The Lancet. That graph combined data from England and from California, USA. The author alleged that this graph illustrated a rise in autism rates linked to the use of the MMR vaccine. By examining the presentation closely, we are able to show how this graph misrepresented the data used. We give advice for both authors and publishers in the use of such graphical treatments of data. PMID- 17867722 TI - Leukotriene receptor antagonists and Churg-Strauss syndrome: cause, trigger or merely an association? AB - Concern has been raised in the medical literature that the use of leukotriene receptor antagonists for the treatment of asthma may be associated with an increased incidence of Churg-Strauss syndrome, a rare small-vessel vasculitic syndrome. This review provides a critical appraisal of the literature to address this question. The incidence of Churg-Strauss syndrome in the general population is one to four cases per million. In patients with asthma it is 20-60 cases per million patient-years, which is similar to that seen in a population receiving leukotriene receptor antagonists. There is no evidence for a direct causative role of leukotriene receptor antagonists in the development of Churg-Strauss syndrome. There may be multiple other non-causative reasons for an association, including the fact that these agents may be initiated in patients who are already in the process of developing Churg-Strauss syndrome, or that the use of leukotriene receptor antagonists leads to a reduction in corticosteroid use, which in turn allows the Churg-Strauss syndrome to be 'unmasked'. PMID- 17867723 TI - Mitochondrial disorders among infants exposed to HIV and antiretroviral therapy. AB - Although antiretroviral therapy (ART) is critical for preventing mother-to-child transmission of HIV, concern has been raised about the possibility that it may cause mitochondrial dysfunction in infants. There is adequate evidence for a mechanism by which exposure to nucleoside reverse transcriptase inhibitors (NRTIs) could lead to mitochondrial dysfunction; animal studies have shown evidence of mitochondrial dysfunction in the offspring of animals treated with NRTIs and mitochondrial disorders occur in adults treated with NRTIs. This systematic review synthesises the published research on mitochondrial dysfunction and disorders in infants exposed to HIV and antiretrovirals. We found conflicting evidence regarding the possible association of in utero ART exposure with mortality and morbidity due to mitochondrial dysfunction. ART exposure in utero or postpartum was associated with persistent decreases in lymphocytes, neutrophils and platelets as well as an increased risk of transient lactic acidaemia, anaemia and mitochondrial DNA depletion, although these laboratory findings were generally not associated with clinical symptoms. We conclude that large, prospective studies of HIV-exposed infants are needed to resolve the discrepant results regarding morbidity and mortality related to mitochondrial disorders, to ascertain the clinical significance of effects on laboratory values, to determine whether or not the incidence of mitochondrial disorders differs by regimen and to develop predictive models that might identify which infants are at the greatest risk. The challenges that remain to be addressed include the development of a sensitive but affordable screening algorithm in combination with specific diagnostic criteria; consistent collection of data on ART exposure and other risk factors, long-term follow-up of HIV-exposed but uninfected children and implementation in resource-limited settings. PMID- 17867725 TI - An analysis of Vigimed, a global e-mail system for the exchange of pharmacovigilance information. AB - BACKGROUND AND AIM: The Internet provides novel ways for communication and data exchange between national regulators. One innovation was the introduction of Vigimed, an e-mail discussion forum for national pharmacovigilance centres (NPCs). We reviewed a sample of Vigimed messages to learn more about this new tool and about the problems encountered in everyday pharmacovigilance and how these are handled. METHODS: We analysed the contents of 100 subsequent questions and the corresponding responses as stored in the Vigimed datafile. RESULTS: To the 100 questions circulated through Vigimed, 575 answers were received; mean number of answers per question 6, range 0-20. Fifty-five (77%) of the 71 collaborating countries and 88 (43%) of the 204 individuals who had access in the study period had submitted at least one question or answer. These countries were in all parts of the world and in various phases of development. A total of 38% of the questions concerned the regulatory status of a drug; 30% safety issues; 13% regulatory actions under consideration; and 10% drug use-related problems (more than one category possible). Of the questions, 89% concerned established drugs; 11% were classified as new. A total of 90% of the questions concerned specific active substances or drug groups. Of the drugs, 73% were classified as 'orthodox' and 9% as herbal; 4% were vaccines and 4% excipients. Emerging drug groups (anatomical therapeutic chemical codes) were NSAIDs and analgesics (M01, N02), antibacterials (J01), antiobesity drugs (A08), psychotropic drugs (N05) and antihistamines (R06). DISCUSSION: NPCs operate in a restricted environment and there is little published information about the daily practices and experiences at NPCs. Our study concerned a sample in a limited period in time. In the meantime, the use of Vigimed has greatly expanded. The data in the Vigimed records are subjected to confidentiality in regard to the identities of countries, staff members, drug products and pharmaceutical companies, which limits the presentation of data in a publication. For information about the actions taken to manage the matters and problems raised in Vigimed it would have been necessary to contact the NPCs and acquire follow-up data. CONCLUSIONS: The Vigimed e-mail discussion group was rapidly incorporated into the routines at NPCs in many countries around the world. When two or more persons per country have access, participation increases. The matters raised predominantly refer to regulatory policy, safety concerns and drug use-related problems, and mainly concern established drugs. The latter emphasises the need for persistent monitoring of all drugs. New safety concerns are often sensitive and uncertain; the timely and efficient communication of such suspicions benefits from an environment of confidentiality. The Vigimed records give a unique view of real life pharmacovigilance, of the matters addressed, the problems encountered, the data needed and the ways in which NPCs help each other. Such information can help make pharmacovigilance more efficient and effective. PMID- 17867726 TI - Impact of safety alerts on measures of disproportionality in spontaneous reporting databases: the notoriety bias. AB - BACKGROUND: Disproportionality analysis of spontaneous reporting is increasingly used, but it may be influenced in unknown ways by safety alerts (notoriety bias). OBJECTIVE: To explore the consequences of safety alerts on reporting disproportionality. METHODS: Within the French national pharmacovigilance database, disproportionality of reporting was tested, using the reporting odds ratio (ROR) and its 95% confidence interval, before and after four safety alerts: valvulopathies with pergolide; tuberculosis with infliximab; strokes with atypical antipsychotics; and rhabdomyolysis with HMG-CoA reductase inhibitors (statins) [after cerivastatin withdrawal]. RESULTS: No cases of valvulopathy were reported in association with pergolide before the safety alert and 63 cases were reported after the alert, (ROR 9400; 95% CI 4300, 20 000), of which five had occurred before the alert. Twenty-five reports mentioned rhabdomyolysis associated with statins (not including cerivastatin) before the safety alert (ROR 5.8; 95% CI 3.8, 9.0), and 63 did so after the alert (ROR 9.4; 95% CI 7.0, 13.0). Approximately 280 cases involving cerivastatin were reported after its withdrawal. There were two reports of tuberculosis associated with infliximab before the alert (ROR 1500; 95% CI 130, 18 000) and seven after the alert (ROR 430; 95% CI 110, 1700). There was one report of a stroke in association with atypical antipsychotic treatment before the safety alert (ROR 0.10; 95% CI 0.01, 0.63) and 16 after the alert (ROR 1.10; 95% CI 0.70, 1.90). After excluding events involving treatment with anticoagulant agents, the RORs for stroke in association with atypical antipsychotic treatment were 0.14 (95% CI 0.02, 1.00) before the alert and 2.0 (95% CI 1.2, 3.4) after the alert. CONCLUSION: Disproportionality in spontaneous reporting databases increases after a safety alert because of increased reporting of the event of interest, including reports of such events that occurred before the alert. This may overflow to increased reporting of the event in association with other drugs. PMID- 17867727 TI - Malaria pharmacovigilance in Africa: lessons from a pilot project in Mpumalanga Province, South Africa. AB - BACKGROUND AND OBJECTIVES: Prior to the introduction of artemisinin-based combination antimalarial therapy in Mpumalanga province, South Africa, a pharmacovigilance strategy was developed to pilot locally relevant surveillance methods for detecting serious adverse drug reactions (ADRs) and signals related to artesunate plus sulfadoxine/pyrimethamine. STUDY DESIGN: From 1 March 2002 to 30 June 2004, five methods for detecting ADRs in patients receiving antimalarials were piloted in the rural communities of Mpumalanga province in South Africa: (i) home follow-up of patients by malaria control staff; (ii) enhanced spontaneous reporting of suspected ADRs by health professionals at clinics and hospitals; (iii) active hospital surveillance for malaria-related admissions and patients recently treated for malaria; (iv) a confidential enquiry into malaria-related deaths; and (v) adverse events monitoring during two therapeutic efficacy studies conducted in 2002 and 2004. RESULTS: During the study period, the malaria control programme was notified of 4778 cases of malaria while sulfadoxine/pyrimethamine monotherapy was the recommended treatment and 7692 cases after the introduction of artesunate plus sulfadoxine/pyrimethamine in January 2003. Of 2393 home follow up visits of reported cases of malaria, three fatal adverse events were identified where recent use of artesunate plus sulfadoxine/pyrimethamine treatment was reported. Two cases were attributed to poor response to treatment, while one case was considered possibly related to artesunate plus sulfadoxine/pyrimethamine treatment. Clinic and hospital surveillance reported six ADRs in association with sulfadoxine/pyrimethamine treatment, five being treatment failures and one being a non-serious rash. During active hospital surveillance, 38 inpatients exposed to sulfadoxine/pyrimethamine were identified, including one child who experienced pancytopenia following treatment with sulfadoxine/pyrimethamine 11 days before admission; this adverse effect was considered to be possibly due to sulfadoxine/pyrimethamine treatment. The confidential enquiry into malaria-related deaths identified three adverse events, including a death where the contribution of treatment could not be excluded. A therapeutic efficacy study of 95 patients followed over 42 days identified one case of repeated vomiting possibly associated with artesunate plus sulfadoxine/pyrimethamine. CONCLUSION: Multifaceted monitoring throughout the malaria patient journey is necessary in developing countries implementing new treatments to safeguard against missing serious complications associated with malaria treatment. PMID- 17867724 TI - Corticosteroid-induced adverse events in adults: frequency, screening and prevention. AB - Corticosteroids represent the most important and frequently used class of anti inflammatory drugs and are the reference therapy for numerous neoplastic, immunological and allergic diseases. However, their substantial efficacy is often counter-balanced by multiple adverse events. These corticosteroid-induced adverse events represent a broad clinical and biological spectrum from mild irritability to severe and life-threatening adrenal insufficiency or cardiovascular events. The purpose of this article is to provide an overview of the available data regarding the frequency, screening and prevention of the adverse events observed in adults during systemic corticosteroid therapy (topically administered corticosteroids are outside the remit of this review). These include clinical (i.e. adipose tissue redistribution, hypertension, cardiovascular risk, osteoporosis, myopathy, peptic ulcer, adrenal insufficiency, infections, mood disorders, ophthalmological disorders, skin disorders, menstrual disorders, aseptic necrosis, pancreatitis) and biological (i.e. electrolytes homeostasis, diabetogenesis, dyslipidaemia) events. Lastly, data about the prescription of corticosteroids during pregnancy are provided. This review underscores the absence of data on many of these adverse events (e.g. lipodystrophy, dyslipidaemia). Our intent is to present to practitioners data that can be used in a practical way to both screen and prevent most of the adverse events observed during systemic corticosteroid therapy. PMID- 17867730 TI - Dynamics of the F2+CH3SCH3 reaction: a molecule-molecule reaction without entrance barrier. AB - The F(2)+CH(3)SCH(3) reaction was studied with crossed molecular beam techniques and high level ab initio calculations. Significant reactivity was observed even at low collision energies, consistent with the negligible barrier height obtained from the ab initio calculations. All experimental findings are consistent with a weakly bound reaction intermediate of F-F-S(CH(3))(2) structure, which possesses a special type of three-center four-electron bonding. Analogous intermediates can also explain the reactions of F(2) with CH(3)SH and CH(3)SSCH(3). PMID- 17867728 TI - The relationship between number of drugs and potential drug-drug interactions in the elderly: a study of over 600,000 elderly patients from the Swedish Prescribed Drug Register. AB - BACKGROUND: Drug-drug interactions (DDIs) are of great concern, as they are known to be related to adverse drug reactions and hospitalisations. In addition, many DDIs are regarded as predictable and avoidable; therefore, they may be considered as targets for education and interventions. OBJECTIVE: To analyse the relationship between number of dispensed drugs and the probability of potential DDIs among the elderly by using the new Swedish Prescribed Drug Register. METHODS: We analysed data on age, sex and dispensed drugs for people aged > or = 75 years who were registered in the Swedish Prescribed Drug Register from October to December 2005, and constructed a list of current prescriptions for every individual on the arbitrarily chosen date of 31 December 2005. Thereafter, we included those who had at least two dispensed drugs to capture the elderly population at risk of being exposed to DDIs (n = 630 743). The main outcome measures were potentially clinically relevant DDIs (type C), which may require dose adjustment, and potentially serious DDIs (type D), which should be avoided. RESULTS: The prevalence of type C potential DDIs was 26% and of type D potential DDIs 5% in the study population. There was a strong association between number of dispensed drugs and the probability of type C potential DDIs and an even stronger association for type D potential DDIs, after adjustment for age and sex. In addition, the probability of type D potential DDIs decreased with increasing age, and women had a lower probability of type D potential DDIs than men. CONCLUSION: There seems to be a strong relationship between number of dispensed drugs and potential DDIs, especially for potentially serious DDIs, which has implications for the importance of trying to minimise the number of drugs prescribed in the elderly. Our findings that the probability of potentially serious DDIs decreases with increasing age among the elderly and that elderly women have a lower probability of potentially serious DDIs than elderly men need to be verified and investigated by further research. PMID- 17867731 TI - Binomial tau-leap spatial stochastic simulation algorithm for applications in chemical kinetics. AB - In cell biology, cell signaling pathway problems are often tackled with deterministic temporal models, well mixed stochastic simulators, and/or hybrid methods. But, in fact, three dimensional stochastic spatial modeling of reactions happening inside the cell is needed in order to fully understand these cell signaling pathways. This is because noise effects, low molecular concentrations, and spatial heterogeneity can all affect the cellular dynamics. However, there are ways in which important effects can be accounted without going to the extent of using highly resolved spatial simulators (such as single-particle software), hence reducing the overall computation time significantly. We present a new coarse grained modified version of the next subvolume method that allows the user to consider both diffusion and reaction events in relatively long simulation time spans as compared with the original method and other commonly used fully stochastic computational methods. Benchmarking of the simulation algorithm was performed through comparison with the next subvolume method and well mixed models (MATLAB), as well as stochastic particle reaction and transport simulations (CHEMCELL, Sandia National Laboratories). Additionally, we construct a model based on a set of chemical reactions in the epidermal growth factor receptor pathway. For this particular application and a bistable chemical system example, we analyze and outline the advantages of our presented binomial tau-leap spatial stochastic simulation algorithm, in terms of efficiency and accuracy, in scenarios of both molecular homogeneity and heterogeneity. PMID- 17867732 TI - Combining two-body density correlation functionals with multiconfigurational wave functions using natural orbitals and occupation numbers. AB - We propose a procedure that combines multiconfigurational (MC) wave functions with two-body density correlation functionals by transforming the latter into functionals of the MC natural orbitals and occupation numbers. The method is tested with the spectroscopic constants of a set of 11 diatomics, the diradical involved automerization barrier of cyclobutadiene, the energy difference between triplet and open-shell singlet states in He and the methylene molecule, and the magnetic coupling constants of several systems, such as NiO, KNiF(3), K(2)NiF(4), La(2)CuO(4), alpha-4-dehydrotoluene, 1,1('),5,5(')-tetramethyl-6,6(')-dioxo 3,3(')-biverdazyl, [Cu(2)Cl(6)](-2), copper(II) acetate monohidrate and H-He-H. The procedure is applied to the Colle-Salvetti [Theor. Chim. Acta 37, 329 (1975); 53, 55 (1979)], functional and to a size-consistent functional depending on the on-top pair density (F1-5-N(eff)). On average, the best results are provided by the transformed F1-5-N(eff) [J. Chem. Phys. 114, 2022 (2001)] functional. PMID- 17867733 TI - Path ensembles and path sampling in nonequilibrium stochastic systems. AB - Markovian models based on the stochastic master equation are often encountered in single molecule dynamics, reaction networks, and nonequilibrium problems in chemistry, physics, and biology. An efficient and convenient method to simulate these systems is the kinetic Monte Carlo algorithm which generates continuous time stochastic trajectories. We discuss an alternative simulation method based on sampling of stochastic paths. Utilizing known probabilities of stochastic paths, it is possible to apply Metropolis Monte Carlo in path space to generate a desired ensemble of stochastic paths. The method is a generalization of the path sampling idea to stochastic dynamics, and is especially suited for the analysis of rare paths which are not often produced in the standard kinetic Monte Carlo procedure. Two generic examples are presented to illustrate the methodology. PMID- 17867734 TI - Cumulant reconstruction of the three-electron reduced density matrix in the anti Hermitian contracted Schrodinger equation. AB - Differing perspectives on the accuracy of three-electron reduced-density-matrix (3-RDM) reconstruction in nonminimal basis sets exist in the literature. This paper demonstrates the accuracy of cumulant-based reconstructions, developed by Valdemoro (V) [F. Colmenero et al., Phys. Rev. A 47, 971 (1993)], Nakatsuji and Yasuda (NY) [Phys. Rev. Lett. 76, 1039 (1996)], Mazziotti (M) [Phys. Rev. A 60, 3618 (1999)], and Valdemoro-Tel-Perez-Romero (VTP) [Many-electron Densities and Density Matrices, edited by J. Cioslowski (Kluwer, Boston, 2000)]. Computationally, we extend previous investigations to study a variety of molecules, including LiH, HF, NH(3), H(2)O, and N(2), in Slater-type, double zeta, and polarized double-zeta basis sets at both equilibrium and nonequilibrium geometries. The reconstructed 3-RDMs, compared with 3-RDMs from full configuration interaction, demonstrate in nonminimal basis sets the accuracy of the first-order expansion (V) as well as the important role of the second-order corrections (NY, M, and VTP). Calculations at nonequilibrium geometries further show that cumulant functionals can reconstruct the 3-RDM from a multireferenced 2 RDM with reasonable accuracy, which is relevant to recent multireferenced formulations of the anti-Hermitian contracted Schrodinger equation (ACSE) and canonical diagonalization. Theoretically, we perform a detailed perturbative analysis of the M functional to identify its second-order components. With these second-order components we connect the M, NY, and VTP reconstructions for the first time by deriving both the NY and VTP functionals from the M functional. Finally, these 3-RDM reconstructions are employed within the ACSE [D. Mazziotti, Phys. Rev. Lett. 97, 143002 (2006)] to compute ground-state energies which are compared with the energies from the contracted Schrodinger equation and several wave function methods. PMID- 17867735 TI - Dynamical effects in line shapes for coupled chromophores: time-averaging approximation. AB - For an isolated resonance of an isolated chromophore in a condensed phase, the absorption line shape is often more sharply peaked than the distribution of transition frequencies as a result of motional narrowing. The latter arises from the time-dependent fluctuations of the transition frequencies. It is well known that one can incorporate these dynamical effects into line shape calculations within a semiclassical approach. For a system of coupled chromophores, both the transition frequencies and the interchromophore couplings fluctuate in time. In principle one can again solve this more complicated problem with a related semiclassical approach, but in practice, for large numbers of chromophores, the computational demands are prohibitive. This has led to the development of a number of approximate theoretical approaches to this problem. In this paper we develop another such approach, using a time-averaging approximation. The idea is that, for a single chromophore, a motionally narrowed line shape can be thought of as a distribution of time-averaged frequencies. This idea is developed and tested on both stochastic and more realistic models of isolated chromophores, and also on realistic models of coupled chromophores, and it is found that in all cases this approximation is quite satisfactory, without undue computational demands. This approach should find application for the vibrational spectroscopy of neat liquids, and also for proteins and other complicated multichromophore systems. PMID- 17867736 TI - Making four- and two-component relativistic density functional methods fully equivalent based on the idea of "from atoms to molecule". AB - It is shown that four- and two-component relativistic Kohn-Sham methods of density functional theory can be made fully equivalent in all the aspects of simplicity, accuracy, and efficiency. In particular, this has been achieved based solely on physical arguments rather than on mathematical tricks. The central idea can be visualized as "from atoms to molecule," reflecting that the atomic information is employed to "synthesize" the molecular no-pair relativistic Hamiltonian. That is, the molecular relativistic Hamiltonian can, without loss of accuracy, be projected onto the positive energy states of the isolated Dirac atoms with the projector approximated simply by the superposition of the atomic ones. The dimension of the four-component Hamiltonian matrix then becomes the same as that of a two-component one. Another essential ingredient is to formulate quasirelativistic theory on matrix form rather than on operator form. The resultant quasi-four-component, normalized elimination of the small component, and symmetrized elimination of the small component approaches are critically examined by taking the molecules of MH and M(2) (M=At, E117) as examples. PMID- 17867737 TI - Canonical transformation theory from extended normal ordering. AB - The canonical transformation theory of Yanai and Chan [J. Chem. Phys. 124, 194106 (2006)] provides a rigorously size-extensive description of dynamical correlation in multireference problems. Here we describe a new formulation of the theory based on the extended normal ordering procedure of Mukherjee and Kutzelnigg [J. Chem. Phys. 107, 432 (1997)]. On studies of the water, nitrogen, and iron oxide potential energy curves, the linearized canonical transformation singles and doubles theory is competitive in accuracy with some of the best multireference methods, such as the multireference averaged coupled pair functional, while computational timings (in the case of the iron oxide molecule) are two to three orders of magnitude faster and comparable to those of the complete active space second-order perturbation theory. The results presented here are greatly improved both in accuracy and in cost over our earlier study as the result of a new numerical algorithm for solving the amplitude equations. PMID- 17867738 TI - Time-dependent density functional theory based upon the fragment molecular orbital method. AB - Time-dependent density functional theory (TDDFT) was combined with the two-body fragment molecular orbital method (FMO2). In this FMO2-TDDFT scheme, the system is divided into fragments, and the electron density for fragments is determined self-consistently. Consequently, only one main fragment of interest and several fragment pairs including it are calculated by TDDFT. To demonstrate the accuracy of FMO2-TDDFT, we computed several low-lying singlet and triplet excited states of solvated phenol and polyalanine using our method and the standard TDDFT for the full system. The BLYP functional with the long-range correction (LC-BLYP) was employed with the 6-31G(*) basis set (some tests were also performed with 6 311G(*), as well as with B3LYP and time-dependent Hartree-Fock). Typically, FMO2 TDDFT reproduced the full TDDFT excitation energies within 0.1 eV, and for one excited state the error was about 0.2 eV. Beside the accurate reproduction of the TDDFT excitation energies, we also automatically get an excitation energy decomposition analysis, which provides the contributions of individual fragments. Finally, the efficiency of our approach was exemplified on the LC-BLYP6-31G(*) calculation of the lowest singlet excitation of the photoactive yellow protein which consists of 1931 atoms, and the obtained value of 3.1 eV is in agreement with the experimental value of 2.8 eV. PMID- 17867739 TI - Langevin dynamics of molecules with internal rigid fragments in the harmonic regime. AB - An approximation scheme is developed to compute Brownian motion according to the Langevin equation for a molecular system moving in a harmonic force field (corresponding to a quadratic potential energy surface) and characterized by one or more rigid internal fragments. This scheme, which relies on elements of the rotation translation block (RTB) method for computing vibrational normal modes of large molecules developed by Sanejouand and co-workers [Biopolymers 34, 759 (1994); Proteins: Struct., Funct., Genet. 41, 1 (2000)], provides a natural and efficient way to freeze out the small amplitude, high frequency motions within each rigid fragment. The number of dynamical degrees of freedom in the problem is thereby reduced, often dramatically. To illustrate the method, the relaxation kinetics of the small membrane-bound ion channel protein gramicidin-A, subjected to an externally imposed impulse, is computed. The results obtained from all-atom dynamics are compared to those obtained using the RTB-Langevin dynamics approximation (treating eight indole moieties as internal rigid fragments): good agreement between the two treatments is found. PMID- 17867740 TI - Energy decompositions according to physical space partitioning schemes: treatments of the density cumulant. AB - This article is a continuation of our previous paper on schemes of energy decompositions of molecular systems in the real space [D. R. Alcoba et al., J. Chem. Phys. 122, 074102 (2005)] now using correlated state functions. We study, according to physical arguments, the appropriate management of the density cumulant arising from the second-order reduced density matrix at correlated level, whose contributions can be assigned to one-center or to two-center terms in the energy partitioning. Our treatments are applied within two physical space partitioning schemes: the Bader partitioning into atomic basins and the fuzzy atom procedure. The results obtained in selected molecules are analyzed and discussed in detail. PMID- 17867741 TI - Photoelectron studies on vibronic coupling in pyrazine. AB - Ionization pathways from the S(1) and T(1) states of pyrazine are investigated using one- and two-photon ionization of the excited state by both resonance enhanced multiphoton ionization photoelectron spectroscopy and zero electron kinetic energy pulsed field ionization techniques. For the triplet manifold, we show that two-photon ionization of T(1) is enhanced by a vibronically induced resonance for which we determine the inducing mode and the nature of the intermediate state, as well as the (3)3s(n(-1)) Rydberg state. For the singlet manifold, we identify the mode responsible for the vibronically induced intensity of a 3p Rydberg state that was previously found to greatly perturb the 1+2(') photoelectron spectrum of S(1) by a resonance at the two-photon level. PMID- 17867742 TI - Searching for resonances in the reaction Cl+CH4-->HCl+CH3: quantum versus quasiclassical dynamics and comparison with experiments. AB - A quantum-mechanical (QM) and quasiclassical trajectory (QCT) study was performed on the title reaction, using a pseudotriatomic ab initio based surface. Probabilities and integral cross sections present some clear peaks versus the collision energy E(col), which we assign to Feshbach resonances of the transition state, where the light H atom oscillates between the heavy Cl and CH(3) groups. For ground-state reactants, reactivity is essentially of quantum origin (QCT observables and oscillations are smaller, or much smaller, than QM ones), and the calculated integral cross section and product distributions are in reasonable agreement with the experiment. The reaction occurs through an abstraction mechanism, following both a direct and an indirect mechanism. The quasiclassical trajectory calculations show the participation of a short-lived collision complex in the microscopic reaction mechanism. Finally, QCT differential cross sections of Cl+CH(4)-->HCl (nu(')=0 and 1)+CH(3) oscillate versus E(col), whereas experimentally this only occurs for HCl (nu(')=1). This theoretical result and other oscillating properties found here could, however, be related to the existence of a Feshbach resonance for the production of HCl (nu(')=1), as suggested by experimentalists. PMID- 17867743 TI - Connection between the virial equation of state and physical clusters in a low density vapor. AB - We carry out Monte Carlo simulations of physical Lennard-Jones and water clusters and show that the number of physical clusters in vapor is directly related to the virial equation of state. This relation holds at temperatures clearly below the critical temperatures, in other words, as long as the cluster-cluster interactions can be neglected--a typical assumption used in theories of nucleation. Above a certain threshold cluster size depending on temperature and interaction potential, the change in cluster work of formation can be calculated analytically with the recently proposed scaling law. The breakdown of the scaling law below the threshold sizes is accurately modeled with the low order virial coefficients. Our results indicate that high order virial coefficients can be analytically calculated from the lower order coefficients when the scaling law for cluster work of formation is valid. The scaling law also allows the calculation of the surface tension and equilibrium vapor density with computationally efficient simulations of physical clusters. Our calculated values are in good agreement with those obtained with other methods. We also present our results for the curvature dependent surface tension of water clusters. PMID- 17867744 TI - Population transfer to excited vibrational levels of H2 molecule by stimulated hyper-Raman passage with chirped laser pulses. AB - We have theoretically investigated the population transfer from the initial ground rovibrational level v(g)=0, J(g)=0 to the final rovibrational levels v(f)=1,2, J(f)=0 of the ground electronic state X (1)Sigma(g) (+) via the resonant intermediate level v(i)=6, J(i)=0 of the excited electronic state EF (1)Sigma(g) (+) of H(2) molecule by (2+2)-photon stimulated hyper-Raman passage (STIHRP). The density matrix technique has been employed to evaluate the population transfer to the final target levels using linearly chirped pump and Stokes laser pulses with different chirp rates. Both the pulses are considered to have the same temporal shape, pulse width, and linear parallel polarizations. We have studied in detail the dependence of the population transfer on the set of laser parameters for pulse (peak) intensities in the ranges of 1.5 x 10(11)-1.0 x 10(12) and 1.0 x 10(12)-7.0 x 10(12) W/cm(2). The corresponding pulse widths (full width at half maximum) are of the order of 115-200 and 15-30 ps. We have found that the chirp rate parameters can be optimized to achieve almost complete population transfer from the ground (g) to the final (f) target levels. This, to our knowledge, is the first application of a (2+2)-photon STIHRP process with chirpings to a model molecular system (H(2)). The study demonstrates the suitability of the chirped (2+2)-photon STIHRP technique for selective and almost total inversion of vibrational population in a diatomic molecule. PMID- 17867745 TI - Potential energy surfaces and Jahn-Teller effect on CH4...NO complexes. AB - The potential energy surface of the CH(4)...NO van der Waals complexes was explored at the RCCSD(T)/aug-cc-pVTZ level including the full counterpoise correction to the basis set superposition error. The Jahn-Teller distortion of the C(3v) configurations for the CH bonded and CH(3) face complexes was analyzed. From this distortion, two A(') and A(") adiabatic surfaces were considered. The estimated zero point energy of C(s) configurations is above the barrier of the C(3v) ones. Therefore, the CH(3) face complexes are dynamic Jahn-Teller systems. The D(0) (140 cm(-1) for A(") state and 100 cm(-1) for A(')) values obtained are in good agreement with the experimental values (103+/-2 cm(-1)) recently reported. PMID- 17867746 TI - Two-body Coulomb explosion and hydrogen migration in methanol induced by intense 7 and 21 fs laser pulses. AB - Two-body Coulomb explosion with the C-O bond breaking of methanol induced by intense laser pulses with the duration of Delta t=7 and 21 fs is investigated by the coincidence momentum imaging method. When Delta t=7 fs, the angular distribution of recoil vectors of the fragment ions for the direct C-O bond breaking pathway, CH(3)OH(2+)-->CH(3) (+)+OH(+), exhibits a peak deflected from the laser polarization direction by 30 degrees -45 degrees , and the corresponding angular distribution for the migration pathway, CH(2)OH(2) (+)- >CH(2) (+)+H(2)O(+), in which one hydrogen migrates from the carbon site to the oxygen site prior to the C-O bond breaking, exhibits almost the same profile. When the laser pulse duration is stretched to Delta t=21 fs, the angular distributions for the direct and migration pathways exhibit a broad peak along the laser polarization direction probably due to the dynamical alignment and/or the change in the double ionization mechanism; that is, from the nonsequential double ionization to the sequential double ionization. However, the extent of the anisotropy in the migration pathway is smaller than that in the direct pathway, exhibiting a substantial effect of hydrogen atom migration in the dissociative ionization of methanol interacting with the linearly polarized intense laser field. PMID- 17867747 TI - Vibrational structure, spin-orbit splitting, and bond dissociation energy of Cl2+(X2 Pi g) studied by zero kinetic energy photoelectron spectroscopy and ion pair formation imaging method. AB - The isotopomer-resolved vibrational and spin-orbit energy structures of Cl(2) (+)(X (2)Pi(g)) have been studied by one-photon zero kinetic energy photoelectron spectroscopy. The spin-orbit energy splitting for the ground vibrational state is determined as 717.7+/-1.5 cm(-1), which greatly improves on the accuracy of the previously reported data. This value is found to be in good agreement with the ab initio quantum chemical calculation taking account of the inner shell electron correlation. The first adiabatic ionization energy (IE) of Cl(2) is determined as 92 645.9+/-1.0 cm(-1). Using the ion-pair formation imaging method to discriminate signals of Cl(+)((1)D(2)) from those of Cl(+)((3)P(j)), the threshold for ion-pair (E(tipp)) production, Cl(+)((1)D(2))+Cl(-)((1)S(0))<- Cl(2)(X (1)Sigma(g) (+)), is determined as 107 096(-2) (+8) cm(-1). By using the determined IE and E(tipp) for Cl(2) and also the reported IE and electronic affinity for chlorine atom, the bond dissociation energies of Cl(2)(X (1)Sigma(g) (+)) and Cl(2) (+)(X (2)Pi(g)) have been determined as 19 990(-2) (+8) and 31 935.1(-2) (+8), respectively. PMID- 17867748 TI - Theoretical study of the stability of multiply charged C70 fullerenes. AB - We have calculated the electronic energies and optimum geometries of C(70) (q+) and C(68) (q+) fullerenes (q=0-14) by means of density functional theory. The ionization energies for C(70) and C(68) fullerenes increase more or less linearly as functions of charge, consistent with the previously reported behavior for C(60) and C(58) [S. Diaz-Tendero et al., J. Chem. Phys. 123, 184306 (2005)]. The dissociation energies corresponding to the C(70) (q+)-->C(68) (q+)+C(2), C(70) (q+)-->C(68) ((q-1)+)+C(2) (+), C(70) (q+)-->C(68) ((q-2)+)+C(+)+C(+), C(70) (q+) ->C(68) ((q-3)+)+C(2+)+C(+), and C(70) (q+)-->C(68) ((q-4)+)+C(2+)+C(2+) decay channels show that C(70) (q+) (like C(60) (q+)) is thermodynamically unstable for q>or=6. However, the slope of the dissociation energy as a function of charge for a given decay channel is different from that of C(60) (q+) fullerenes. On the basis of these results, we predict q=17 to be the highest charge state for which a fission barrier exists for C(70) (q+). PMID- 17867749 TI - On the simulation of photoelectron spectra in molecules with conical intersections and spin-orbit coupling: the vibronic spectrum of CH3S. AB - A method to simulate photoelectron spectra for states coupled by conical intersections and the spin-orbit interaction is reported. The algorithm is based on the multimode vibronic coupling model and treats the spin-orbit interaction in a nonperturbative manner. Since the algorithm is not dependent on molecular symmetry, the approach is generally applicable to accidental conical intersections as well as the symmetry required intersections found in Jahn-Teller molecules. The method is also computationally efficient using energy gradient and derivative coupling information to limit the number of nuclear configurations at which ab initio data are required. This approach is applied to simulate the negative ion photoelectron spectrum of the methylthio radical. The two-state Hamiltonian employed to describe this system was determined employing ab initio gradients and derivative couplings at only 17 nuclear configurations. PMID- 17867750 TI - Quasiclassical trajectory calculations of the OH+NO2 association reaction on a global potential energy surface. AB - We report a full-dimensional potential energy surface (PES) for the OH+NO(2) reaction based on fitting more than 55,000 energies obtained with density functional theory-B3LYP6-311G(d,p) calculations. The PES is invariant with respect to permutation of like nuclei and describes all isomers of HOONO, HONO(2), and the fragments OH+NO(2) and HO(2)+NO. Detailed comparison of the structures, energies, and harmonic frequencies of various stationary points on the PES are made with previous and present high-level ab initio calculations. Two hydrogen-bond complexes are found on the PES and confirmed by new ab initio CASPT2 calculations. Quasiclassical trajectory calculations of the cross sections for ground rovibrational OH+NO(2) association reactions to form HOONO and HONO(2) are done using this PES. The cross section to form HOONO is larger than the one to form HONO(2) at low collision energies but the reverse is found at higher energies. The enhancement of the HOONO complex at low collision energies is shown to be due, in large part, to the transient formation of a H-bond complex, which decays preferentially to HOONO. The association cross sections are used to obtain rate constants for formation of HOONO and HONO(2) for the ground rovibrational states in the high-pressure limit. PMID- 17867751 TI - Energy transfer of highly vibrationally excited naphthalene. I. Translational collision energy dependence. AB - Energy transfer between highly vibrationally excited naphthalene and Kr atom in a series of translational collision energies (108-847 cm(-1)) was studied separately using a crossed-beam apparatus along with time-sliced velocity map ion imaging techniques. Highly vibrationally excited naphthalene in the triplet state (vibrational energy: 16,194 cm(-1); electronic energy: 21,400 cm(-1)) was formed via the rapid intersystem crossing of naphthalene initially excited to the S(2) state by 266 nm photons. The collisional energy transfer probability density functions were measured directly from the scattering results of highly vibrationally excited naphthalene. At low collision energies a short-lived naphthalene-Kr complex was observed, resulting in small amounts of translational to vibrational-rotational (T-->VR) energy transfer. The complex formation probability decreases as the collision energy increases. T-->VR energy transfer was found to be quite efficient at all collision energies. In some instances, nearly all of the translational energy is transferred to vibrational-rotational energy. On the other hand, only a small fraction of vibrational energy is converted to translational energy. The translational energy gained from vibrational energy extend to large energy transfer (up to 3000 cm(-1)) as the collision energy increases to 847 cm(-1). Substantial amounts of large V-->T energy transfer were observed in the forward and backward directions at large collision energies. PMID- 17867752 TI - Electronic spectroscopy of jet-cooled HCP+: molecular structure, phosphorus hyperfine structure, and Renner-Teller analysis. AB - Laser-induced fluorescence spectra of jet-cooled HCP(+) and DCP(+) have been obtained with the pulsed discharge technique using HCPDCP and argon precursor mixtures. Transitions involving all of the excited state vibrations have been observed and a set of vibrational constants has been obtained. High-resolution spectra of the (2)Pi(32) components of the 0(0) (0) bands of both isotopomers have been recorded, and these spectra show resolved phosphorus hyperfine structure which allowed the determination of the excited state Fermi contact parameter. The B values were used to obtain the ground and excited state effective geometric parameters as r(0) (")(CH)=1.077(2) A, r(0) (")(CP)=1.6013(3) A, r(0) (')(CH)=1.082(2) A, and r(0) (')(CP)=1.5331(3) A. A Renner-Teller analysis of the ground state vibrational energy levels obtained from the literature was attempted. All of the observed levels of DCP(+) and the majority of those of HCP(+) were satisfactorily fitted with a standard Renner-Teller model, but three HCP(+) levels showed large systematic deviations which could not be accommodated by reassignments or improvements in the Fermi resonance Hamiltonian. Further improvements in the theory or in the experimental data will be needed to resolve this discrepancy. PMID- 17867753 TI - Calculated spectroscopic and electric properties of the alkali metal-ammonia complexes from Kn-NH3 to Frn-NH3 (n=0,+1). AB - The newly developed Stuttgart small-core scalar relativistic pseudopotentials for the alkali metals are used to study spectroscopic and electric properties of the heavier alkali metal-ammonia complexes from K(n)-NH(3) to Fr(n)-NH(3) (n=0,+1) at the second-order Moller-Plesset (MP2) and coupled cluster [CCSD(T)] levels of theory. Equilibrium geometries and dissociation energies computed at the MP2 level are in reasonable agreement with their CCSD(T) counterparts, whereas for the dipole polarizabilities MP2 is not performing well overestimating significantly electron correlation effects. The bond distances increase monotonically with increasing mass of the metal atom as relativistic effects are small in these systems. However, the dipole polarizabilities are more sensitive to such effects and we find a decrease in this property from Cs-NH(3) to Fr NH(3). Combination of CCSD(T) harmonic frequencies and MP2 anharmonic corrections obtained from a perturbative vibrational treatment leads to fundamental frequencies in good agreement with experimental results obtained by Suzer and Andrews [J. Am. Chem. Soc. 109, 300 (1986)]. We also present the results of variational calculations with a three-dimensional vibrational Hamiltonian, making use of CCSD(T) potential energy and electric dipole moment surfaces. Complexation of NH(3) to the metal causes a strong infrared intensification of the symmetric NH(3) stretching mode in the neutral complexes, which is absent in the charged species. PMID- 17867754 TI - Atomiclike ionization and fragmentation of a series of CH3-X (X: H, F, Cl, Br, I, and CN) by an intense femtosecond laser. AB - Methane derivatives of CH(3)-X (X: H, F, Cl, Br, I, and CN) were ionized and fragmented by an intense femtosecond laser with a 40 fs pulse at 0.8 microm in intensities of 10(13)-10(15) W cm(-2). The curves of the ionization yields of CH(3)-X versus laser intensities have been found to be fitted with an atomic ionization theory (the theory of Perelomov, Popov, and Terent'ev) that has been established to reproduce experimental results well for rare gas atoms. The saturation intensities have been reproduced within a factor of 1.6 of the calculated ones. For molecules with low ionization potentials such as amines, another atomic ionization theory (the theory of Ammosov, Delone, and Krainov) reproduced the saturation intensities. The atomiclike ionization behavior of molecules indicates that the fragmentation occurs after the ionization. The fragmentation mechanisms after the ionization of some molecular ions are discussed. PMID- 17867755 TI - Effect of matrix on IR frequencies of acetylene and acetylene-methanol complex: infrared matrix isolation and ab initio study. AB - Effect of nitrogen and argon matrices on the C-H asymmetric stretching and bending infrared frequencies of the acetylene molecule, C(2)H(2), has been studied by matrix isolation experiments as well as by calculations at MP2 level of theory. The complexes of C(2)H(2) in nitrogen and argon matrices, viz., C(2)H(2)(N(2))(m) (with m=2-8) and C(2)H(2)(Ar)(n) (with n=2-10) are theoretically explored. The computed acetylenic C-H asymmetric stretch in C(2)H(2)-nitrogen complexes shows a redshift of 3.0 to 11.9 cm(-1) compared with the frequencies of the free acetylene molecule, and a corresponding blueshift of 7.4 to 26.2 cm(-1) when C(2)H(2) is complexed with argon atoms. The trends in the computed shifts are in good agreement with the experiments. The molecular electrostatic potential minimum of C(2)H(2) becomes more negative when complexed with nitrogen than on complexation with argon. This observation implies a greater basic character for C(2)H(2) in the nitrogen matrix, favoring the formation of H pi(C(2)H(2)-MeOH) complex as compared to that in the Ar matrix. Experimentally the preferential formation of H-pi(C(2)H(2)-MeOH) complex in the N(2) matrix has indeed been observed. PMID- 17867756 TI - Clustering of Lennard-Jones particles in water: temperature and pressure effects. AB - While the hydrophobic effect is, for many systems, one of the most relevant interactions, it may be said that in the case of biological systems this effect becomes of determinant importance. Although the matter has been analyzed extensively, certain aspects are yet to be elucidated. Hence, the study on the behavior of the hydrophobic effect with temperature, and particularly with pressure deserves further investigation; model systems may help us in the task. We have analyzed the behavior of Lennard-Jones particles in water by means of molecular dynamics simulation under different conditions of size, concentration, temperature, and pressure. Following the formation of particle aggregates we can observe an increase of the hydrophobic effect with temperature and a strong weakening of the effect at high pressures. The results agree with the experimental evidence and show the ability of molecular dynamics simulation to account for the behavior of nonpolar substances under different conditions, provided that the intermolecular interactions used are adequate. PMID- 17867757 TI - Emission of Au nanoparticles with and without rhodamine 6G dye. AB - We have observed Stokes and anti-Stokes emission of Au nanoparticles suspended in methanol and rhodamine 6G dye solution. Photoluminescence of Au nanoparticles is a three-step process involving single-photon or three-photon excitation of electron-hole pairs, relaxation of excited electrons and holes, and emission from electron-hole recombination, possibly enhanced by surface plasmons. In the presence of dye, the excitation of anti-Stokes emission of gold involves two photon absorption in rhodamine 6G molecules followed by the energy transfer to Au nanoparticles with simultaneous absorption of one pumping photon by Au. This mechanism significantly enhances anti-Stokes emission of gold nanoparticles in the presence of dye. PMID- 17867758 TI - Melting line of the Lennard-Jones system, infinite size, and full potential. AB - Literature estimates of the melting curve of the Lennard-Jones system vary by as much as 10%. The origin of such discrepancies remains unclear. We present precise values for the Lennard-Jones melting temperature, and we examine possible sources of systematic errors in the prediction of melting points, including finite-size and interaction-cutoff effects. A hypothetical thermodynamic integration path is used to find the relative free energies of the solid and liquid phases, for various system sizes, at constant cutoff radius. The solid-liquid relative free energy and melting temperature scale linearly as the inverse of the number of particles, and it is shown that finite-size effects can account for deviations in the melting temperature (from the infinite-size limit) of up to 5%. An extended ensemble density-of-states method is used to determine free energy changes for each phase as a continuous function of the cutoff radius. The resulting melting temperature predictions exhibit an oscillatory behavior as the cutoff radius is increased. Deviations in the melting temperature (from the full potential limit) arising from a finite cutoff radius are shown to be of comparable magnitude as those resulting from finite-size effects. This method is used to identify melting temperatures at five different pressures, for the infinite-size and full potential Lennard-Jones system. We use our simulation results as references to connect the Lennard-Jones solid equation of state of van der Hoef with the Lennard-Jones fluid equation of state of Johnson. Once the references are applied the two equations of state are used to identify a melting curve. An empirical equation that fits this melting curve is provided. We also report a reduced triple point temperature T(tr)=0.694. PMID- 17867759 TI - Heat capacity of the liquid-liquid mixture nitrobenzene and dodecane near the critical point. AB - The heat capacity of the liquid-liquid mixture nitrobenzene-dodecane has been measured for the first time near its upper critical consolute point using an adiabatic calorimeter. The theoretical expression for the heat capacity near the critical point was applied to our combined data runs. The critical exponent alpha was determined to be 0.124+/-0.006, which was consistent with theoretical predictions. When alpha was fixed at its theoretical value of 0.11, our value for the amplitude ratio A(+)A(-)=0.58+/-0.02 was consistent with experimental determinations and theoretical predictions. However, the two-scale-factor universality ratio X, now consistent among experiments and theories with a value between 0.019 and 0.020, was violated in this system when using a previously published value for the correlation length. PMID- 17867760 TI - Rotational dynamics of water and benzene controlled by anion field in ionic liquids: 1-butyl-3-methylimidazolium chloride and hexafluorophosphate. AB - The rotational correlation time (tau(2R)) is determined for D(2)O (polar) and C(6)D(6) (apolar) in 1-butyl-3-methylimidazolium chloride ([bmim][Cl]) and hexafluorophosphate ([bmim][PF(6)]) by measuring (2)H (D) nuclear magnetic resonance spin-lattice relaxation time (T(1)) in the temperature range from -20 to 110 degrees C. The tau(2R) ratio of water to benzene (tau(WB)) was used as a measure of solute-solvent attraction. tau(WB) is 0.73 and 0.52 in [bmim][Cl] and [bmim][PF(6)], respectively, whereas the molecular volume ratio is as small as 0.11. The slowdown of the water dynamics compared to the benzene dynamics in ionic liquids is interpreted by the Coulombic attractive interaction between the polar water molecule and the anion. As for the anion effect, the rotational dynamics of water solvated by Cl(-) is slower than that solvated by PF(6) (-), whereas the rotational dynamics of benzene is similar in the two ionic liquids. This is interpreted as an indication of the stronger solvation by the anion with a larger surface charge density. The slowdown of the water dynamics via Coulombic solvation is actually significant only at water concentrations lower than approximately 9 mol dm(-3) at room temperature, and it is indistinguishable at temperatures above approximately 100 degrees C. The quadrupolar coupling constants determined for D(2)O and C(6)D(6) in the ionic liquids were smaller by a factor of 2-3 than those in the pure liquid state. PMID- 17867761 TI - Effective interaction of nonuniformly charged colloid spheres in a bulk electrolyte. AB - The interaction energy between two like-charged colloid spheres with nonuniformly distributed surface charges immersed in a bulk electrolyte is calculated under the linearized Poisson-Boltzmann equation. The calculated results are sensitive to the relative orientations of the spheres due to the anisotropy of the distribution of charges on the sphere surface. The effective repulsive interaction after thermal average is weaker than the case when charges are uniformly distributed on the spheres, and with the increase of the nonuniformity, an attractive interaction between the two spheres emerges. PMID- 17867762 TI - A new model for Overhauser enhanced nuclear magnetic resonance using nitroxide radicals. AB - Nitroxide free radicals are the most commonly used source for dynamic nuclear polarization (DNP) enhanced nuclear magnetic resonance (NMR) experiments and are also exclusively employed as spin labels for electron spin resonance (ESR) spectroscopy of diamagnetic molecules and materials. Nitroxide free radicals have been shown to have strong dipolar coupling to (1)H in water, and thus result in large DNP enhancement of (1)H NMR signal via the well known Overhauser effect. The fundamental parameter in a DNP experiment is the coupling factor, since it ultimately determines the maximum NMR signal enhancements which can be achieved. Despite their widespread use, measurements of the coupling factor of nitroxide free radicals have been inconsistent, and current models have failed to successfully explain our experimental data. We found that the inconsistency in determining the coupling factor arises from not taking into account the characteristics of the ESR transitions, which are split into three (or two) lines due to the hyperfine coupling of the electron to the (14)N nuclei (or (15)N) of the nitric oxide radical. Both intermolecular Heisenberg spin exchange interactions as well as intramolecular nitrogen nuclear spin relaxation mix the three (or two) ESR transitions. However, neither effect has been taken into account in any experimental studies on utilizing or quantifying the Overhauser driven DNP effects. The expected effect of Heisenberg spin exchange on Overhauser enhancements has already been theoretically predicted and observed by Bates and Drozdoski [J. Chem. Phys. 67, 4038 (1977)]. Here, we present a new model for quantifying Overhauser enhancements through nitroxide free radicals that includes both effects on mixing the ESR hyperfine states. This model predicts the maximum saturation factor to be considerably higher by the effect of nitrogen nuclear spin relaxation. Because intramolecular nitrogen spin relaxation is independent of the nitroxide concentration, this effect is still significant at low radical concentrations where electron spin exchange is negligible. This implies that the only correct way to determine the coupling factor of nitroxide free radicals is to measure the maximum enhancement at different concentrations and extrapolate the results to infinite concentration. We verify our model with a series of DNP experimental studies on (1)H NMR signal enhancement of water by means of (14)N as well as (15)N isotope enriched nitroxide radicals. PMID- 17867763 TI - ac response of a carbon chain under a finite frequency bias. AB - Based on nonequilibrium Green's function approach and density functional theory, we report first principles investigation on ac transport of four carbon atom chain connected by two semi-infinite aluminum leads Al-C(4)-Al. For small alternating external bias voltage, we expanded nonequilibrium Green's function to the first order in the external voltage and calculated the dynamical conductance. The suppression of the dynamic conductance was obtained near the resonant level while far away from the resonance the giant enhancement of the dynamic conductance was also observed. These behaviors can be well understood under the wide-band limit. By changing the coupling distance between the carbon atom and aluminum leads, the system could change its transport response between capacitivelike and inductivelike. PMID- 17867764 TI - Surface tension and capillary waves at the nematic-isotropic interface in ternary mixtures of liquid crystal, colloids, and impurities. AB - In mixtures of thermotropic liquid crystals with spherical poly(methyl methacrylate) particles, self-supporting networklike structures are formed during slow cooling past the isotropic-to-nematic phase transition. Experimental results support the hypothesis that a third component, alkane remnants slowly liberated from the particles, plays a crucial role. A theoretical model, based on the phenomenological Landau-de Gennes, Carnahan-Starling, and hard-sphere crystal theories, is developed to describe the continuous phase separation in a ternary nematic-impurity-colloid mixture. The interfacial tension and the dispersion relation of the surface modes of the nematic-isotropic interface are determined. The colloids decrease the interfacial tension and the damping rate of surface waves, whereas impurities act in an opposite way. This should strongly influence the formation of abovementioned networklike structures and could help explain some of their rheological properties. PMID- 17867765 TI - Free energies of CO2H2 capture by p-tert-butylcalix[4]arene: a molecular dynamics study. AB - The interactions of CO(2)H(2) with p-tert-butylcalix[4]arene (TBC4) were studied using potential of mean force (PMF) and free energy perturbation approaches. To the best of our knowledge, the present work is one of the first to employ the constrained mean force approach to evaluate solute selectivity by the TBC4 molecule. The computed PMFs for the interaction of CO(2)H(2) with a single TBC4 molecule establish that the interaction of CO(2) with the open end of the cage structure is attractive while the interaction with H(2) is repulsive. Free energy perturbation calculations were performed for the same two guest molecules with a pair of facing TBC4 molecules used as a representative model as found in the TBC4 molecular solid. At low temperature, both CO(2)H(2) have favorable interactions with the TBC4 pair, with the CO(2) interaction being considerably greater. These results are in agreement with recent experimental data showing considerable CO(2) uptake by TBC4 at moderate pressures. PMID- 17867766 TI - Structure of incommensurate gold sulfide monolayer on Au(111). AB - We develop an atomic-scale model for an ordered incommensurate gold sulfide (AuS) adlayer which has previously been demonstrated to exist on the Au(111) surface, following sulfur deposition and annealing to 450 K. Our model reproduces experimental scanning tunneling microscopy images. Using state-of-the-art Wannier function-based techniques, we analyze the nature of bonding in this structure and provide an interpretation of the unusual stoichiometry of the gold sulfide layer. The proposed structure and its chemistry have implications for related S-Au interfaces, as in those involved in self-assembled monolayers of thiols on Au substrates. PMID- 17867767 TI - Ab initio embedded cluster study of the excitation spectrum and Stokes shifts of Bi3+-doped Y2O3. AB - The ab initio embedded cluster method coupled with correlated spin-orbit calculations has been used to interpret the excitation spectrum of a Bi(3+)-doped yttria crystal. Our results indicate that the Bi(3+) impurity can absorb light over a wider energy range in the C(2) site than in the S(6) site. Even if the computed absorption energies seem to be about 0.4 eV too high with respect to the experimental peaks for both sites, it is noteworthy that the embedded cluster model renders 93% of the large crystal redshift, about 6 eV. The determination of the geometry relaxation of the first shell of oxygen neighbors upon electronic excitation shows that the Stokes shift is smaller in the S(6) site than in the C(2) site. Combining all these results confirms the assignment of the violet emission to the S(6) site and that of the green emission to the C(2) site, as proposed by Boulon [J. Phys. (Paris) 32, 333 (1971)]. In addition, the nature of the metastable states which lie below the emitting ones and are responsible for the temperature dependence of the fluorescence lifetimes is discussed. PMID- 17867768 TI - Atomistic simulations of calcite nanoparticles and their interaction with water. AB - Molecular dynamics (MD) simulations have been used to study the stability of calcite nanoparticles ranging in size from 18 to 324 f.u., both in vacuo and in the presence of explicit water molecules. In vacuo, the smallest particles become highly disordered during the MD simulation due to rotation and translation of the undercoordinated CO(3) (2-) anions at the edges of the particles. As the nanoparticle size increases, the influence of the fully coordinated bulk ions begins to dominate and long-range order is seen both in the Ca-C pair distribution functions and in the degree of rotational order of the CO(3) (2-) anions. However, when explicit water is added to the system, the molecules in the first hydration layer complete the coordination shell of the surface ions, preserving structural order even in the smallest of the nanoparticles. Close to particle surface, the structure of the water itself shows features similar to those seen close to planar periodic (1014) surfaces, although the molecules are far less tightly bound. PMID- 17867769 TI - Influence of aggregation, defects, and contaminant oxygen on water dissociation at Cu(110) surface: a theoretical study. AB - The DFT-PW91 slab model approach is employed to investigate the influence of aggregation, surface defects, and contaminant oxygen on water dissociation on Cu(110) at low temperatures. The dissociation barriers of water in various aggregate states are calculated in the range of 60-75 kJ/mol on the clean surfaces, in nice agreement with the experimentally determined values. It is revealed that the aggregation of water shows no propensity to reduce the activation barrier for the O-H bond breaking on Cu(110), at variance with the water chemistry on Ru(0001). The calculated activation energy on Cu(211) which is the most active stepped surface investigated is equal to the value on the (110) surface, indicating that the hydroxyl groups observed on Cu(110) at low temperatures may not stem from surface defects. The coadsorbed oxygen, whether as a "spectator" or a "participant," facilitates the water dissociation both kinetically and thermodynamically. PMID- 17867770 TI - Electric double layer effect on observable characteristics of the tunnel current through a bridged electrochemical contact. AB - Scanning tunneling microscopy and electrical conductivity of redox molecules in conducting media (aqueous or other media) acquire increasing importance both as novel single-molecule science and with a view on molecular scale functional elements. Such configurations require full and independent electrochemical potential control of both electrodes involved. We provide here a general formalism for the electric current through a redox group in an electrochemical tunnel contact. The formalism applies broadly in the limits of both weak and strong coupling of the redox group with the enclosing metal electrodes. Simple approximate expressions better suited for experimental data analysis are also derived. Particular attention is given to the effects of the Debye screening of the electric potential in the narrow tunneling gap based on the limit of the linearized Poisson-Boltzmann equation. The current/overpotential relation shows a maximum at a position which depends on the ionic strength. It is shown, in particular, that the dependence of the maximum position on the bias voltage may be nonmonotonous. Approximate expressions for the limiting value of the slope of the current/overpotential dependence and the width of the maximum on the bias voltage are also given and found to depend strongly on both the Debye screening and the position of the redox group in the tunnel gap, with diagnostic value in experimental data analysis. PMID- 17867771 TI - First-principles calculations of hydrogen diffusion on rutile TiO2(110) surfaces. AB - Density functional calculations are performed to study the H-atom diffusion on titanium dioxide (110) surface in the cases of water-molecule dissociation and splitting of the adjacent hydroxyl OH pair. It is shown that, when a water molecule is adsorbed at a surface oxygen-vacancy site, a fragment H atom of the water molecule tends to diffuse toward the nearest-neighboring bridging-oxygen sites by using a straight-line or relay-point path. As the result, a pair of surface hydroxyl OH is formed on the same oxygen row. In a thermal process, on the other hand, such OH pair favorably splits only by using a relay-point path, i.e., by transferring one H atom from a bridging-oxygen site to a next neighboring one along the same oxygen row by way of another in-plane oxygen site. We found that the latter splitting reaction is activated around room temperature. PMID- 17867772 TI - Intraband spectroscopy and band offsets of colloidal II-VI core/shell structures. AB - The interband and intraband spectra of colloidal II-VI CdS and CdSe quantum dot cores and CdSZnSe, CdSCdSe, CdSeCdS, and CdSeZnSe core/shell systems are reported. Infrared absorption peaks between 0.5 and 0.2 eV are observed. The slope of the intraband energy versus the first interband absorption feature is characteristic of the relative band alignments of the materials constituting the core and the shell and it is analyzed within an effective mass model. The analysis provides a new estimate of the band gap of zinc blende CdSe as well as the band offsets in zinc blende and wurtzite CdSe, CdS, and ZnSe. PMID- 17867773 TI - Statistical approaches to the transient populations and to the macroscopic energy transfer rate for the upconversion phenomenon in monodoped amorphous solid. AB - In this article, statistical approaches to the first and the second excited state transient populations and to the temporal macroscopic energy transfer rate for the upconversion process in amorphous solid generic systems monodoped with trivalent lanthanide ions are reached. The plots of the expressions show general tendencies reported in the literature. The derivation and the analysis of the formalism allowed us to fulfill our main objective, that is, to make a theoretical study about the microscopic and statistical mechanisms present in the phenomenon and their relation with the classic kinetic analysis. The study shows that the inclusion of the minimum possible radius between two optical centers in a solid affects the initial slopes of the decay curves of the luminescence from the intermediate state. We also corroborate that the usual treatment of experimental data using direct equations for the dynamics of the populations in laser pulsed excitation experiments falls in the mistake of not considering the temporality of the macroscopic energy transfer rate. Finally, physical explanations are formulated about this temporal behavior and about the main factors that generate the characteristic simple exponential decay loss of the luminescence from the intermediate state. PMID- 17867774 TI - Influence of dye molecules on the birefringence of liquid crystal mixtures at near infrared frequencies. AB - The optical properties of nematic liquid crystals have been extensively exploited in the production of devices working in the visible range of the spectrum. These same properties can be employed to make devices that function in the near infrared as required for telecommunications applications. However, it is generally observed that the birefringence of liquid crystal mixtures decreases with increasing wavelength, making it important to identify new materials, optimized for use in the near infrared region. One route to high birefringence is to operate close to an absorption band edge, which in the present context implies choosing highly conjugated materials which are potentially colored and, thus, not suited to traditional display applications. In this paper we explore the usefulness of dye molecules as birefringence enhancers in mixtures with conventional nematic liquid crystals. The optical properties, in particular, the absorption edge, polarizability, and birefringence, of families of known dyes are calculated at optical (589 nm) and infrared (1550 nm) wavelengths, using electronic density functional theory. We demonstrate the expected correlation between the proximity of the absorption edge and the magnitude of the birefringence, and estimate the birefringence enhancement occurring when each dye is incorporated in a guest-host system. PMID- 17867775 TI - Point and ring defects in nematics under capillary confinement. AB - The textures exhibited by nematic liquid crystals confined to cylindrical capillaries under homeotropic anchoring have been studied for nearly thirty years. One of the reasons behind this maintained interest is that the processing of many high-performance fibers including carbon fibers and spider silks involves these textures. Three of these textures, the planar radial with line defect, the planar polar with two line defects (PPLD), and the escape radial (ER), are relatively well understood. A third one, the escape radial with point defects presents, however, some unresolved issues and recent studies have questioned the real nature and dimensionality of the defects involved in this texture. It seems that the defects are not in the form of points but rather in the form of closed lines or rings. This paper presents a detailed study on the connection between point and ring defects in a cylindrical cavity using three-dimensional simulations based on the continuum Landau-de Gennes theory. The results show that true point defects cannot exist in cylindrical cavities and that the merging of two ringlike defects may lead to two qualitatively different stable textures, namely, the ER and PPLD textures. The various results are in qualitative agreement with recent molecular dynamic studies and with theoretical predictions based on experimental observations. The predictions provide new insights on the structural connections between synthetic and biological superfibers. PMID- 17867776 TI - Phenomenological model for the confined dynamics in semicrystalline polymers: the multiple alpha relaxation in cold-crystallized poly(ethylene terephthalate). AB - The segmental relaxation in poly(ethylene terephthalate), crystallized from either an isotropic or a cold-drawn glass, is investigated by means of dielectric spectroscopy. It is shown that there exist two distinct alpha relaxation modes: a slow one, characterized by a rather wide frequency interval, and a faster, much narrower one. A simple phenomenological model is developed in order to analyze the polarization autocorrelation functions phi(t)'s associated with these relaxation modes. The model is based on the idea that the growth of crystalline domains causes a progressive confinement of the amorphous regions where, eventually, the observed alpha processes take place. The mechanism of confinement is accounted for by applying to the case of constrained density fluctuations, well known concepts introduced by Adam and Gibbs [J. Chem. Phys. 43, 139 (1965)] concerning the relaxation dynamics in liquids close to the glass transition. Randomness on confining conditions is then introduced, leading to the derivation of analytical expressions which are used afterwards to fit the asymptotic behavior of the phi's for long-time tails. It is found that the slow, broad alpha process takes place in regions where the confining effect of crystals is strong, whereas the amorphous domains relaxing via the fast mode are those where the confinement effect of crystals is weak. The analysis of the phi's by means of this model allows us to relate the fitting exponents to the dispersion in the free energy associated with structural rearrangement. PMID- 17867777 TI - Counterion-counterion correlation in the double layer around cylindrical polyions: counterion size and valency effects. AB - Monte Carlo simulation and Poisson-Boltzmann results on some aspects of structure and thermodynamics of aqueous polyelectrolyte solutions are presented. The polyelectrolyte solution is described by an infinitely long cylindrical polyion surrounded by counterions modeled as rigid ions moving in a continuum dielectric. Ion-ion correlations in the form of volume average of the counterion-counterion distribution function in the double layer surrounding the polyion are reported for mono- and divalent counterions and for a range of polyion concentrations and charge density parameters in each case. These results confirm again strong influence of the charge density parameter of polyions on properties of polyelectrolyte solutions. The structural information is supplemented by the calculated thermodynamic properties such as osmotic coefficients and heats of dilutions; the latter quantity has not been examined yet in detail by computer simulations. The results are discussed in view of the existing experimental data from the literature for these properties. PMID- 17867778 TI - Raman spectroscopy of intermolecular charge transfer complex between a conjugated polymer and an organic acceptor molecule. AB - Intermolecular donor-acceptor charge transfer complex (CTC) formed in the electronic ground state between poly[2-methoxy-5-(2-ethylhexyloxy)-1,4 phenylenevinylene] (MEH-PPV) and 2,4,7-trinitrofluorenone (TNF) has been investigated by Raman and optical absorption spectroscopies. Blending of MEH-PPV and TNF results in appearance of the CTC absorption band in the optical gap of the both components and in changes in the characteristic MEH-PPV Raman bands including shifts, change in bandwidth, and intensity. The experimental data are similar in films and solutions indicating the CTC formation in both. We associate the low-frequency shift of the strongest MEH-PPV Raman band at approximately 1580 cm(-1) reaching 5 cm(-1) with partial electron transfer from MEH-PPV to TNF amounting approximately 0.2e(-). We suggest that polymer conjugated segments can form the CTC of variable composition MEH-PPV:TNF=1:X, where X0.7 GPa) in all cases. From the Brillouin frequency shifts, longitudinal and transverse sound speeds were calculated, as were the C(11) and C(12) elastic constants, bulk, shear, and Young's moduli, and Poisson's ratios, and their respective pressure dependencies. P-V isotherms were then constructed, and fit to several empirical/semiempirical equations of state to extract the isothermal bulk modulus and its pressure derivative for each material. Finally, the lack of shear waves observed for any polymer at ambient pressure, and the pressure dependency of their appearance is discussed with regard to instrumental and material considerations. PMID- 17867780 TI - Multistage adsorption of diffusing macromolecules and viruses. AB - We derive the equations that describe adsorption of diffusing particles onto a surface followed by additional surface kinetic steps before being transported across the interface. Multistage surface kinetics occurs during membrane protein insertion, cell signaling, and the infection of cells by virus particles. For example, viral entry into healthy cells is possible only after a series of receptor and coreceptor binding events occurs at the cellular surface. We couple the diffusion of particles in the bulk phase with the multistage surface kinetics and derive an effective, integrodifferential boundary condition that contains a memory kernel embodying the delay induced by the surface reactions. This boundary condition takes the form of a singular perturbation problem in the limit where particle-surface interactions are short ranged. Moreover, depending on the surface kinetics, the delay kernel induces a nonmonotonic, transient replenishment of the bulk particle concentration near the interface. The approach generalizes that of Ward and Tordai [J. Chem. Phys. 14, 453 (1946)] and Diamant and Andelman [Colloids Surf. A 183-185, 259 (2001)] to include surface kinetics, giving rise to qualitatively new behaviors. Our analysis also suggests a simple scheme by which stochastic surface reactions may be coupled to deterministic bulk diffusion. PMID- 17867781 TI - Effects of hydrophobic and dipole-dipole interactions on the conformational transitions of a model polypeptide. AB - We studied the effects of hydrophobicity and dipole-dipole interactions between the nearest-neighbor amide planes on the secondary structures of a model polypeptide by calculating the free energy differences between different peptide structures. The free energy calculations were performed with low computational costs using the accelerated Monte Carlo simulation (umbrella sampling) method, with a bias-potential method used earlier in our accelerated molecular dynamics simulations. It was found that the hydrophobic interaction enhances the stability of alpha helices at both low and high temperatures but stabilizes beta structures only at high temperatures at which alpha helices are not stable. The nearest neighbor dipole-dipole interaction stabilizes beta structures under all conditions, especially in the low temperature region where alpha helices are the stable structures. Our results indicate clearly that the dipole-dipole interaction between the nearest neighboring amide planes plays an important role in determining the peptide structures. Current research provides a more unified and quantitative picture for understanding the effects of different forms of interactions on polypeptide structures. In addition, the present model can be extended to describe DNA/RNA, polymer, copolymer, and other chain systems. PMID- 17867782 TI - Dynamic disorder in single-molecule Michaelis-Menten kinetics: the reaction diffusion formalism in the Wilemski-Fixman approximation. AB - Single-molecule equations for the Michaelis-Menten [Biochem. Z. 49, 333 (1913)] mechanism of enzyme action are analyzed within the Wilemski-Fixman [J. Chem. Phys. 58, 4009 (1973); 60, 866 (1974)] approximation after the effects of dynamic disorder--modeled by the anomalous diffusion of a particle in a harmonic well- are incorporated into the catalytic step of the reaction. The solution of the Michaelis-Menten equations is used to calculate the distribution of waiting times between successive catalytic turnovers in the enzyme beta-galactosidase. The calculated distribution is found to agree qualitatively with experimental results on this enzyme obtained at four different substrate concentrations. The calculations are also consistent with measurements of correlations in the fluctuations of the fluorescent light emitted during the course of catalysis, and with measurements of the concentration dependence of the randomness parameter. PMID- 17867783 TI - Stretching effects on the permeability of water molecules across a lipid bilayer. AB - Using a coarse grained molecular dynamics model of a solvent-surfactant system, we study the effects of stretching on the permeability of water across a lipid bilayer. The density profile, free energy profile, diffusion profile, and tail ordering parameter were computed for a set of stretched membranes maintained at constant area. We computed the water permeability across each membrane using the inhomogeneous solubility-diffusion model first proposed by Marrink and Berendsen [J. Phys. Chem. 98, 4155 (1994)]. We find that even though the resistance to permeation profile shows a great deal of qualitative change as the membranes are stretched, the overall permeability remains nearly constant within the relevant range of stretching. This is explained by the fact that the main barrier to permeation, located in the densest section of the tails, is insensitive to increased area per lipid, as a result of competing effects. Expansion leads to thinning and a higher density in the tail region, the latter leading to an increase in the free energy barrier. However, this is compensated by the reduction in the transverse distance to cross and a larger diffusion coefficient due to increased disordering in the chains. PMID- 17867784 TI - Transient violations of the second law of thermodynamics in protein unfolding examined using synthetic atomic force microscopy and the fluctuation theorem. AB - The synthetic atomic force microscopy (AFM) method is developed to simulate a periodically replicated atomistic system subject to force and length fluctuations characteristic of an AFM experiment. This new method is used to examine the forced-extension and subsequent rupture of the alpha-helical linker connecting periodic images of a spectrin protein repeat unit. A two-dimensional potential of mean force (PMF) along the length and a reaction coordinate describing the state of the linker was calculated. This PMF reveals that the basic material properties of the spectrin repeat unit are sensitive to the state of linker, an important feature that cannot be accounted for in a one-dimensional PMF. Furthermore, nonequilibrium simulations were generated to examine the rupture event in the context of the fluctuation theorem. These atomistic simulations demonstrate that trajectories which are in apparent violation of the second law can overcome unfolding barriers at significantly reduced rupture forces. PMID- 17867785 TI - Rotating magnetic particle microrheometry in biopolymer fluid dynamics: mucus microrheology. AB - The polymer properties of canine mucus were investigated through the method of rotating magnetic particle microrheometry. Mucus is visualized as a physically entangled biopolymer of low polydispersity in a water-based solution. Mucus was modeled according to the constitutive law of a Doi-Edwards fluid. The magnetic particle equation of rotational motion is analytically solved in the linear viscoelastic limit rendering theoretical flow profiles which are used to fit the experimental trace signals of the particle remanent-magnetic-field decay. The zero-shear-rate viscosity was found to be 18,000 P and the relaxation time at about 42 s. The molecular weight between entanglements for mucins was estimated at 1.7 MDa rendering an estimation of about seven physical cross-links per molecule. Rheological investigations were extended also to diluted and concentrated rations of the normal mucus simulating the conditions found in more physiological extremes. PMID- 17867786 TI - Effects of the DNA state fluctuation on single-cell dynamics of self-regulating gene. AB - A dynamical mean-field theory is developed to analyze stochastic single-cell dynamics of gene expression. By explicitly taking account of nonequilibrium and nonadiabatic features of the DNA state fluctuation, two-time correlation functions and response functions of single-cell dynamics are derived. The method is applied to a self-regulating gene to predict a rich variety of dynamical phenomena such as an anomalous increase of relaxation time and oscillatory decay of correlations. The effective "temperature" defined as the ratio of the correlation to the response in the protein number is small when the DNA state change is frequent, while it grows large when the DNA state change is infrequent, indicating the strong enhancement of noise in the latter case. PMID- 17867787 TI - Transition on the entropic elasticity of DNA induced by intercalating molecules. AB - We use optical tweezers to perform stretching experiments on DNA molecules when interacting with the drugs daunomycin and ethidium bromide, which intercalate the DNA molecule. Our results show that the persistence length of the DNA-drug complexes increases strongly as the drug concentration increases up to some critical value. Above this critical value, the persistence length decreases abruptly and remains approximately constant for larger drug concentrations, at least in the concentration range used in our experiments. Measured intercalators critical concentrations for the persistence length transition coincide with the reported values for the helix-coil transition of DNA-drug complexes obtained from sedimentation experiments. The contour length of the molecules increases monotonically and saturates as the drug concentration increases. The neighbor exclusion model fits to our results for the total drug concentration as a function of the relative increase of the contour length. PMID- 17867789 TI - Three-dimensional nonlinear optical endoscopy. AB - The development of miniaturized nonlinear optical microscopy or endoscopy is essential to complement the current imaging modalities for diagnosis and monitoring of cancers. We report on a nonlinear optical endoscope based on a double-clad photonic crystal fiber and a two-dimensional (2-D) microelectromechanical system mirror, enabling the three-dimensional (3-D) nonlinear optical imaging through in vitro gastrointestinal tract tissue and human breast cancer tissue with a penetration depth of approximately 100 mum and axial resolution of 10 mum. The 3-D high-resolution and high-sensitive imaging ability of the nonlinear optical endoscope facilitates the visualization of 3-D morphologic and cell nuclei arrangement within tissue, and therefore will be important for histopathologic interpretation without the need of tissue excision. PMID- 17867791 TI - Ultrahigh-resolution imaging of human donor cornea using full-field optical coherence tomography. AB - A feasibility study of ultrahigh-resolution full-field optical coherence tomography (FF-OCT) for a subcellular-level imaging of human donor corneas is presented. The FF-OCT system employed in this experiment is based on a white light interference microscope, where the sample is illuminated by a thermal light source and a horizontal cross-sectional (en face) image is detected using a charge coupled device (CCD) camera. A conventional four-frame phase-shift detection technique is employed to extract the interferometric image from the CCD output. A 95-nm-broadband full-field illumination yields an axial resolution of 2.0 microm, and the system covers an area of 850 microm x 850 microm with a transverse resolution of 2.4 microm using a 0.3-NA microscope objective and a CCD camera with 512 x 512 pixels. Starting a measurement from the epithelial to the endothelial side, a series of en face images was obtained. From detected en face images, the epithelial cells, Bowman's layer, stromal keratocyte, nerve fiber, Descemet's membrane, and endothelial cell were clearly observed. Keratocyte cytoplasm, its nuclei, and its processes were also separately detected. Two dimensional interconnectivity of the keratocytes is visualized, and the keratocytes existing between collagen lamellaes are separately extracted by exploiting a high axial resolution ability of FF-OCT. PMID- 17867792 TI - Dynamic analysis of chemical eye burns using high-resolution optical coherence tomography. AB - The use of high-resolution optical coherence tomography (OCT) to visualize penetration kinetics during the initial phase of chemical eye burns is evaluated. The changes in scattering properties and thickness of rabbit cornea ex vivo were monitored after topical application of different corrosives by time-resolved OCT imaging. Eye burn causes changes in the corneal microstructure due to chemical interaction or change in the hydration state as a result of osmotic imbalance. These changes compromise the corneal transparency. The associated increase in light scattering within the cornea is observed with high spatial and temporal resolution. Parameters affecting the severity of pathophysiological damage associated with chemical eye burns like diffusion velocity and depth of penetration are obtained. We demonstrate the potential of high-resolution OCT for the visualization and direct noninvasive measurement of specific interaction of chemicals with the eye. This work opens new horizons in clinical evaluation of chemical eye burns, eye irritation testing, and product testing for chemical and pharmacological products. PMID- 17867793 TI - Minimum distance mapping using three-dimensional optical coherence tomography for glaucoma diagnosis. AB - Objective imaging of the optic nerve structure has become central to the management of patients with glaucoma. There is an urgent need in diagnosis and staging for reliable objective precursors and markers. Three-dimensional ultrahigh-resolution frequency domain optical coherence tomography (3D UHR OCT) holds particular promise in this respect since it enables volumetric assessment of intraretinal layers including tomographic data for the retinal nerve fiber layer (RNFL) and optic nerve head. The integrated analysis of this information and the resolution advantage has enabled the development of more informative indices of axonal damage in glaucoma compared with measurements of RNFL thickness and cup-to-disc ratio provided by commercial OCT devices. The potential for UHR OCT in enabling the combined analysis of tomographic and volumetric data on retinal structure is explored. A novel parameter was developed; the three dimensional minimal distance as the optical correlate of true retinal nerve fiber layer thickness around the optic nerve head region. For the purposes of this pilot study, we present data from a normal subject and from two patients with characteristic optic nerve and retinal nerve fiber layer changes secondary to glaucoma. PMID- 17867794 TI - Autocalibration of spectral-domain optical coherence tomography spectrometers for in vivo quantitative retinal nerve fiber layer birefringence determination. AB - Accurate wavelength assignment of each spectral element for spectral-domain optical coherence tomography (SD-OCT) and optical frequency domain imaging (OFDI) is required for proper construction of biological tissue cross-sectional images. This becomes more critical for functional extensions of these techniques, especially in polarization-sensitive optical coherence tomography (PS-OCT), where incorrect wavelength assignment between the two orthogonal polarization channels leads to polarization artifacts. We present an autocalibration method for wavelength assignment that does not require separate calibration measurements and that can be applied directly on actual data. Removal of the birefringence artifact is demonstrated in a PS-OCT system with picometer accuracy in the relative wavelength assignment, resulting in a residual phase error of 0.25 deg/100 microm. We also demonstrate, for the first time, a quantitative birefringence map of an in vivo human retinal nerve fiber layer. PMID- 17867795 TI - Adaptation of a support vector machine algorithm for segmentation and visualization of retinal structures in volumetric optical coherence tomography data sets. AB - Recent developments in Fourier domain-optical coherence tomography (Fd-OCT) have increased the acquisition speed of current ophthalmic Fd-OCT instruments sufficiently to allow the acquisition of volumetric data sets of human retinas in a clinical setting. The large size and three-dimensional (3D) nature of these data sets require that intelligent data processing, visualization, and analysis tools are used to take full advantage of the available information. Therefore, we have combined methods from volume visualization, and data analysis in support of better visualization and diagnosis of Fd-OCT retinal volumes. Custom-designed 3D visualization and analysis software is used to view retinal volumes reconstructed from registered B-scans. We use a support vector machine (SVM) to perform semiautomatic segmentation of retinal layers and structures for subsequent analysis including a comparison of measured layer thicknesses. We have modified the SVM to gracefully handle OCT speckle noise by treating it as a characteristic of the volumetric data. Our software has been tested successfully in clinical settings for its efficacy in assessing 3D retinal structures in healthy as well as diseased cases. Our tool facilitates diagnosis and treatment monitoring of retinal diseases. PMID- 17867796 TI - Analysis of posterior retinal layers in spectral optical coherence tomography images of the normal retina and retinal pathologies. AB - We present a computationally efficient, semiautomated method for analysis of posterior retinal layers in three-dimensional (3-D) images obtained by spectral optical coherence tomography (SOCT). The method consists of two steps: segmentation of posterior retinal layers and analysis of their thickness and distance from an outer retinal contour (ORC), which is introduced to approximate the normal position of external interface of the healthy retinal pigment epithelium (RPE). The algorithm is shown to effectively segment posterior retina by classifying every pixel in the SOCT tomogram using the similarity of its surroundings to a reference set of model pixels from user-selected area(s). Operator intervention is required to assess the quality of segmentation. Thickness and distance maps from the segmented layers and their analysis are presented for healthy and pathological retinas. PMID- 17867797 TI - Enhancing the signal-to-noise ratio in ophthalmic optical coherence tomography by image registration--method and clinical examples. AB - Optical coherence tomography (OCT) has already proven an important clinical tool for imaging and diagnosing retinal diseases. Concerning the standard commercial ophthalmic OCT systems, speckle noise is a limiting factor with respect to resolving relevant retinal features. We demonstrate successful suppression of speckle noise from mutually aligning a series of in vivo OCT recordings obtained from the same retinal target using the Stratus system from Humphrey-Zeiss. Our registration technique is able to account for the axial movements experienced during recording as well as small transverse movements of the scan line from one scan to the next. The algorithm is based on a regularized shortest path formulation for a directed graph on a map formed by interimage (B-scan) correlations. The resulting image enhancement typically increases the contrast-to noise ratio (CNR) with a factor of three or more and facilitates segmentation and quantitative characterization of pathologies. The method is currently successfully being applied by medical doctors in a number of specific retinal case studies. PMID- 17867798 TI - Evaluation of potential image acquisition pitfalls during optical coherence tomography and their influence on retinal image segmentation. AB - The development of improved segmentation algorithms for more consistently accurate detection of retinal boundaries is a potentially useful solution to the limitations of existing optical coherence tomography (OCT) software. We modeled artifacts related to operator errors that may normally occur during OCT imaging and evaluated their influence on segmentation results using a novel segmentation algorithm. These artifacts included: defocusing, depolarization, decentration, and a combination of defocusing and depolarization. Mean relative reflectance and average thickness of the automatically extracted intraretinal layers was then measured. Our results show that defocusing and depolarization errors together have the greatest altering effect on all measurements and on segmentation accuracy. A marked decrease in mean relative reflectance and average thickness was observed due to depolarization artifact in all intraretinal layers, while defocus resulted in a less-marked decrease. Decentration resulted in a marked but not significant change in average thickness. Our study demonstrates that care must be taken for good-quality imaging when measurements of intraretinal layers using the novel algorithm are planned in future studies. An awareness of these pitfalls and their possible solutions is crucial for obtaining a better quantitative analysis of clinically relevant features of retinal pathology. PMID- 17867799 TI - Corneal birefringence compensation for polarization sensitive optical coherence tomography of the human retina. AB - In previous publications we have reported on polarization-sensitive optical coherence tomography (PS-OCT) systems that measure and image retardation and axis orientation of birefringent samples with only a single input polarization state. This method requires that the sample is illuminated by circularly polarized light. In the case of retinal imaging, the retina is measured through the birefringent cornea, which causes a deviation of the sampling beam from the circular polarization state. To obtain undistorted birefringence patterns of the retina by PS-OCT, the corneal birefringence has to be compensated. We report on a software-based corneal birefringence compensation that uses the polarization state of the light backscattered at the retinal surface to measure the corneal birefringence. This information is used to numerically compensate the corneal birefringence. Contrary to hardware-based solutions, our method accounts for local variations of the corneal birefringence. We implemented the method in a state of the art spectral domain PS-OCT system and demonstrate it in a test sample and human retina in vivo. PMID- 17867800 TI - Three-dimensional optical coherence tomography at 1050 nm versus 800 nm in retinal pathologies: enhanced performance and choroidal penetration in cataract patients. AB - Frequency domain optical coherence tomography (FD-OCT), based on an all reflective high-speed InGaAs spectrometer, operating in the 1050 nm wavelength region for retinal diagnostics, enables high-speed, volumetric imaging of retinal pathologies with greater penetration into choroidal tissue is compared to conventional 800 nm three-dimensional (3-D) ophthalmic FD-OCT systems. Furthermore, the lower scattering at this wavelength significantly improves imaging performance in cataract patients, thereby widening the clinical applicability of ophthalmic OCT. The clinical performance of two spectrometer based ophthalmic 3-D OCT systems compared in respect to their clinical performance, one operating at 800 nm with 150 nm bandwidth (approximately 3 microm effective axial resolution) and the other at 1050 nm with 70 nm bandwidth (approximately 7 microm effective axial resolution). Results achieved with 3-D OCT at 1050 nm reveal, for the first time, decisive improvements in image quality for patients with retinal pathologies and clinically significant cataract. PMID- 17867802 TI - Vectorial reconstruction of retinal blood flow in three dimensions measured with high resolution resonant Doppler Fourier domain optical coherence tomography. AB - Resonant Doppler Fourier domain optical coherence tomography (FDOCT) is a functional imaging tool for extracting tissue flow. The method is based on the effect of interference fringe blurring in spectrometer-based FDOCT, where the path difference between structure and reference changes during camera integration. If the reference path length is changed in resonance with the Doppler frequency of the sample flow, the signals of resting structures will be suppressed, whereas the signals of blood flow are enhanced. This allows for an easy extraction of vascularization structure. Conventional flow velocity analysis extracts only the axial flow component, which strongly depends on the orientation of the vessel with respect to the incident light. We introduce an algorithm to extract the vessel geometry within the 3-D data volume. The algorithm calculates the angular correction according to the local gradients of the vessel orientations. We apply the algorithm on a measured 3-D resonant Doppler dataset. For validation of the reproducibility, we compare two independently obtained 3-D flow maps of the same volunteer and region. PMID- 17867801 TI - Spectral oximetry assessed with high-speed ultra-high-resolution optical coherence tomography. AB - We use Fourier domain optical coherence tomography (OCT) data to assess retinal blood oxygen saturation. Three-dimensional disk-centered retinal tissue volumes were assessed in 17 normal healthy subjects. After removing DC and low-frequency a-scan components, an OCT fundus image was created by integrating total reflectance into a single reflectance value. Thirty fringe patterns were sampled; 10 each from the edge of an artery, adjacent tissue, and the edge of a vein, respectively. A-scans were recalculated, zeroing the DC term in the power spectrum, and used for analysis. Optical density ratios (ODRs) were calculated as ODR(Art)=ln(Tissue(855)Art(855))ln(Tissue(805)Art(805)) and ODR(Vein)=ln(Tissue(855)Vein(855))ln(Tissue(805)Vein(805)) with Tissue, Art, and Vein representing total a-scan reflectance at the 805- or 855-nm centered bandwidth. Arterial and venous ODRs were compared by the Wilcoxon signed rank test. Arterial ODRs were significantly greater than venous ODRs (1.007+/-2.611 and -1.434+/-4.310, respectively; p=0.0217) (mean+/-standard deviation). A difference between arterial and venous blood saturation was detected. This suggests that retinal oximetry may possibly be added as a metabolic measurement in structural imaging devices. PMID- 17867803 TI - Real-time spectral domain Doppler optical coherence tomography and investigation of human retinal vessel autoregulation. AB - Investigation of the autoregulatory mechanism of human retinal perfusion is conducted with a real-time spectral domain Doppler optical coherence tomography (SDOCT) system. Volumetric, time-sequential, and Doppler flow imaging are performed in the inferior arcade region on normal healthy subjects breathing normal room air and 100% oxygen. The real-time Doppler SDOCT system displays fully processed, high-resolution [512 (axial) x 1000 (lateral) pixels] B scans at 17 frames/sec in volumetric and time-sequential imaging modes, and also displays fully processed overlaid color Doppler flow images comprising 512 (axial) x 500 (lateral) pixels at 6 frames/sec. Data acquired following 5 min of 100% oxygen inhalation is compared with that acquired 5 min postinhalation for four healthy subjects. The average vessel constriction across the population is -16+/-26% after oxygen inhalation with a dilation of 36+/-54% after a return to room air. The flow decreases by -6+/-20% in response to oxygen and in turn increases by 21+/-28% as flow returns to normal in response to room air. These trends are in agreement with those previously reported using laser Doppler velocimetry to study retinal vessel autoregulation. Doppler flow repeatability data are presented to address the high standard deviations in the measurements. PMID- 17867804 TI - In vivo total retinal blood flow measurement by Fourier domain Doppler optical coherence tomography. AB - There is considerable interest in new methods for the assessment of retinal blood flow for the diagnosis of eye diseases. We present in vivo normal human volumetric retinal flow measurement using Fourier domain Doppler optical coherence tomography. We used a dual-plane scanning pattern to determine the angle between the blood flow and the scanning beam in order to measure total flow velocity. Volumetric flow in each blood vessel around the optic nerve head was integrated in one cardiac cycle in each measurement. Measurements were performed in the right eye of one human subject. The measured venous flow velocity ranged from 16.26 mm/s to 29.7 mm/s. The arterial flow velocity ranged from 38.35 mm/s to 51.13 mm/s. The total retinal venous and arterial flow both added up to approximately 54 microl/min. We believe this is the first demonstration of total retinal blood flow measurement using the OCT technique. PMID- 17867805 TI - Nonlinear optical potentiometric dyes optimized for imaging with 1064-nm light. AB - Nonlinear optical phenomena, such as two-photon fluorescence (2PF) and second harmonic generation (SHG), in combination with voltage sensitive dyes, can be used to acquire high-resolution spatio temporal maps of electrical activity in excitable cells and tissue. Developments in 1064-nm fiber laser technology have simplified the generation of high-intensity, long-wavelength, femtosecond light pulses, capable of penetrating deep into tissue. To merge these two advances requires the design and synthesis of new dyes that are optimized for longer wavelengths and that produce fast and sensitive responses to membrane potential changes. In this work, we have systematically screened a series of new dyes with varying chromophores and sidechains that anchor them in cell membranes. We discovered several dyes that could potentially be used for in vivo measurements of cellular electrical activity because of their rapid and sensitive responses to membrane potential. Some of these dyes show optimal activity for SHG; others for 2PF. This regulated approach to dye screening also allows significant insight into the molecular mechanisms behind both SHG and 2PF. In particular, the differing patterns of sensitivity and kinetics for these two nonlinear optical modalities indicate that their voltage sensitivity originates from differing mechanisms. PMID- 17867806 TI - Quantification of the second-order nonlinear susceptibility of collagen I using a laser scanning microscope. AB - Characteristic changes in the organization of fibrillar collagen can potentially serve as an early diagnostic marker in various pathological processes. Tissue types containing collagen I can be probed by pulsed high-intensity laser radiation, thereby generating second harmonic light that provides information about the composition and structure at a microscopic level. A technique was developed to determine the essential second harmonic generation (SHG) parameters in a laser scanning microscope setup. A rat-tail tendon frozen section was rotated in the xy-plane with the pulsed laser light propagating along the z-axis. By analyzing the generated second harmonic light in the forward direction with parallel and crossed polarizer relative to the polarization of the excitation laser beam, the second-order nonlinear optical susceptibilities of the collagen fiber were determined. Systematic variations in SHG response between ordered and less ordered structures were recorded and evaluated. A 500 microm-thick z-cut lithiumniobate (LiNbO(3)) was used as reference. The method was applied on frozen sections of malignant melanoma and normal skin tissue. Significant differences were found in the values of d(22), indicating that this parameter has a potential role in differentiating between normal and pathological processes. PMID- 17867807 TI - In situ multiphoton optical tomography of hair follicles in mice. AB - We report multiphoton in situ optical sectioning of hair follicles in mice and a preliminary investigation of the pathological hair follicles in a transgenic mouse model. Using this imaging technology, we rapidly obtain detailed three dimensional (3-D) reconstructions of individual hair follicles. No staining or mechanical sectioning is involved, since multiphoton microscopy coregisters two photon excited fluorescence (TPF) from cells and second harmonic generation (SHG) signals from the extracellular matrix (ECM). These signals are ideally suited for estimating molecularly encoded hair follicular 3-D geometries, including sizes of the follicular orifices and their angles relative to the skin surface. In the normal hair follicles, spectral separation of SHG signals generated by the ECM of the hair follicle from that of intrinsic cellular fluorescence revealed intricate spatial interaction of the cellular components with the surrounding connective tissue. In the pathological hair follicles, these were clearly modified. In particular, in the transgenic mice, we observed lack of cellular fluorescence and significantly shallower angles of follicular orifices with respect to the skin surface. The combination of TPF with SHG is sensitive to structural changes in cells and extracellular matrix brought on by normal hair follicle physiology and specific gene alterations. PMID- 17867808 TI - Localized multiphoton photoactivation of paGFP in Drosophila wing imaginal discs. AB - In biological imaging of fluorescent molecules, multiphoton laser scanning microscopy (MPLSM) has become the favorite method of fluorescence microscopy in tissue explants and living animals. The great power of MPLSM with pulsed lasers in the infrared wavelength lies in its relatively deep optical penetration and reduced ability to cause potential nonspecific phototoxicity. These properties are of crucial importance for long time-lapse imaging. Since the excited area is intrinsically confined to the high-intensity focal volume of the illuminating beam, MPLSM can also be applied as a tool for selectively manipulating fluorophores in a known, three-dimensionally defined volume within the tissue. Here we introduce localized multiphoton photoactivation (MP-PA) as a technique suitable for analyzing the dynamics of photoactivated molecules with three dimensional spatial resolution of a few micrometers. Short, intense laser light pulses uncage photoactivatable molecules via multiphoton excitation in a defined volume. MP-PA is demonstrated on photoactivatable paGFP in Drosophila wing imaginal discs. This technique is especially useful for extracting quantitative information about the properties of photoactivatable fusion proteins in different cellular locations in living tissue as well as to label single or small patches of cells in tissue to track their subsequent lineage. PMID- 17867809 TI - Characterization of vulnerable plaques by multiphoton microscopy. AB - Cardiovascular disease is the primary cause of death in the United States; the majority of these deaths are caused by the rupture of vulnerable plaques. An important feature of vulnerable plaques is the thickness of the fibrous cap that covers the necrotic core. A thickness of less than 65 microm has been proposed as a value that renders the plaque prone to rupture. This work shows that multiphoton microscopy (MPM) can image the plaque with microm resolution to a depth deeper than 65 microm. The fibrous cap emits primarily second harmonic generation due to collagen, in contrast to the necrotic core and healthy artery, which emits primarily two-photon excited fluorescence from elastin. This gives a good demarcation of the fibrous cap from underlying layers, facilitating the measurement of the fibrous cap thickness. Based on a measure of the collagen/elastin ratio, plaques were detected with a sensitivity of 65% and specificity of 81%. Furthermore, the technique gives detailed information on the structure of the collagen network in the fibrous cap. This network ultimately determines the mechanical strength of the plaque. A mechanical model based on this information could yield a measure of the propensity of the plaque to rupture. PMID- 17867810 TI - Multimodal optical microscope for detecting viability of mouse embryos in vitro. AB - We present a multimodal optical microscope that incorporates six imaging modalities on one common platform. The imaging modalities include three staring modes, optical quadrature microscopy (OQM), differential interference contrast (DIC) microscopy, and epi-fluorescence microscopy, and three scanning modes, confocal reflectance microscopy (CRM), confocal fluorescence microscopy (CFM), and two-photon microscopy (2PM). OQM reconstructs the amplitude and phase of an optically transparent specimen within a modified Mach-Zehnder configuration. DIC microscopy images the phase gradient along a specified direction of an optically transparent specimen. CRM detects index of refraction changes that modulate backscatter. Epi-fluorescence microscopy, CFM, and 2PM detect endogenous and exogenous fluorophores within a specimen. The scanning modes are inherently capable of producing three-dimensional (3-D) images due to optical sectioning and localized probing. Illumination and imaging are performed coaxially with minimal changes of optical components between modes. Multimodal images of embryos are shown to demonstrate the microscope's imaging capabilities. PMID- 17867811 TI - Theoretical and practical considerations on detection performance of time domain, Fourier domain, and swept source optical coherence tomography. AB - Optical coherence tomography (OCT) based on spectral interferometry has recently been examined, with authors often suggesting superior performance compared with time domain approaches. The technologies have similar resolutions and the spectral techniques may currently claim faster acquisition rates. Contrary to many current opinions, their detection parameters may be inferior. The dynamic range and signal-to-noise ratio (SNR) correlate with image penetration, the contrast as a function of depth. This work examines the theoretical sensitivity, dynamic range, and SNR of the techniques, within the practical limits of optoelectronics, taking into account often ignored or misunderstood classical factors that affect performance, such as low frequency noise, analog to digital (AD) conversion losses, and methods for potentially improving sensitivity, including fast laser sweeping. The technologies are compared relative to these parameters. While Fourier domain OCT has some advantages such as signal integration, it appears unlikely that its disadvantages can ultimately be overcome for nontransparent tissue. Ultimately, time-domain (TD)-OCT appears to have the superior performance with respect to SNR and dynamic range. This may not be the case for transparent tissue of the eye. Certain positive aspects of swept source OCT leave the possibility open that its performance may approach that of (TD)-OCT in nontransparent tissue. PMID- 17867812 TI - Spectral domain phase microscopy for local measurements of cytoskeletal rheology in single cells. AB - We present spectral domain phase microscopy (SDPM) as a new tool for measurements at the cellular scale. SDPM is a functional extension of spectral domain optical coherence tomography that allows for the detection of cellular motions and dynamics with nanometer-scale sensitivity in real time. Our goal was to use SDPM to investigate the mechanical properties of the cytoskeleton of MCF-7 cells. Magnetic tweezers were designed to apply a vertical force to ligand-coated magnetic beads attached to integrin receptors on the cell surfaces. SDPM was used to resolve cell surface motions induced by the applied stresses. The cytoskeletal response to an applied force is shown for both normal cells and those with compromised actin networks due to treatment with Cytochalasin D. The cell response data were fit to several models for cytoskeletal rheology, including one and two-exponential mechanical models, as well as a power law. Finally, we correlated displacement measurements to physical characteristics of individual cells to better compare properties across many cells, reducing the coefficient of variation of extracted model parameters by up to 50%. PMID- 17867813 TI - Micro-resonance Raman study of optically trapped Escherichia coli cells overexpressing human neuroglobin. AB - We describe the possibility of using a microresonance Raman spectrometer combined with a microfluidic system and optical tweezers to study Escherichia coli (E. coli) overexpressing wild type (wt) neuroglobin (NGB) and its E7Leu mutant, respectively. NGB is a recently discovered heme protein and its function still is a matter of debate. So far, the protein has been studied in its purified form, and in vivo measurements on the single cell level could give more information. To study the feasibility of the combined techniques, the possibilities of the setup are investigated by taking spectra from single cells and clusters of cells. We find that the microresonance Raman technique enables studies of the wt NGB protein in a living cell under fluctuating aerobic and anaerobic conditions. E. coli cells overexpressing wt NGB are stable, and the reversible oxygenation deoxygenation can be studied over a long period of time. Further, the experiment indicates the presence of an enzymatic system in the bacteria reducing the ferric form NGB. The study of E. coli cells overexpressing E7Leu NGB, on the other hand, gives insight into limiting factors of the setup, such as cell lysis, photoinduced chemistry, and protein concentrations. PMID- 17867814 TI - Chemical imaging of the stratum corneum under controlled humidity with the attenuated total reflection Fourier transform infrared spectroscopy method. AB - Attenuated total reflection Fourier transform infrared spectroscopic imaging was applied to study human stratum corneum (SC) tissue, the outermost layer of the skin. This imaging approach was combined with a controlled environment cell to demonstrate the possibility of obtaining chemical images of SC exposed to a wide range of relative humidities and diffusion of ethanol through the SC tissue with a specially designed liquid cell. The effect of water vapor sorbed into the SC on the distribution of other components in the SC was studied. Principal component analysis was applied in conjunction with univariate analysis to differentiate the distribution of different components in the SC. Swelling of the SC, a heterogeneous distribution of natural moisturizing factor and water, was detected upon the increase of relative humidity. The approach to image the penetration of liquid ethanol into the SC was also demonstrated and showed good potential and implications for studying transdermal drug delivery. PMID- 17867815 TI - Experimental evaluation of angularly variable fiber geometry for targeting depth resolved reflectance from layered epithelial tissue phantoms. AB - The present study focuses on enhancing the sensitivity and specificity of spectral diagnosis in a stratified architecture that models human cervical epithelia by experimentally demonstrating the efficacy of using angularly variable fiber geometry to achieve the desired layer selection and probing depths. The morphological and biochemical features of epithelial tissue vary in accordance with tissue depths; consequently, the accuracy of spectroscopic diagnosis of epithelial dysplasia may be enhanced by probing the optical properties of this tissue. In the case of cellular dysplasia, layer-specific changes in tissue optical properties may be optimally determined by reflectance spectroscopy when specifically coupled with angularly variable fiber geometry. This study addresses the utility of using such angularly variable fiber geometry for resolving spatially specific spectra of a two-layer epithelial tissue phantom. Spectral sensitivity to the scattering particles embedded in the epithelial phantom layer is shown to significantly improve as the obliquity of the collection fibers increases from 0 to 40 deg. Conversely, the orthogonal fibers are found to be more sensitive to changes in the stromal phantom layer. PMID- 17867816 TI - Targeting spectral signatures of progressively dysplastic stratified epithelia using angularly variable fiber geometry in reflectance Monte Carlo simulations. AB - A key component of accurate spectroscopic-based cancer diagnostics is the ability to differentiate spectral variations resulting from epithelial tissue dysplasia. Such measurement may be enhanced by discretely probing the optical properties of the epithelial tissue where the morphological and biochemical features vary according to tissue depths. More precisely, layer-specific changes in tissue optical properties correlated to cellular dysplasia can be determined by conventional reflectance spectroscopy when it is coupled with angularly variable fiber geometry. Thus, this study addresses how angularly variable fiber geometry can resolve spatially specific spectral signatures of tissue pathology by interpreting and analyzing the reflectance spectra of increasingly dysplastic epithelial tissue in reflectance-mode Monte Carlo simulation. Specifically, by increasing the obliquity of the collection fibers from 0 to 40 deg in the direction facing toward the illumination fiber, the spectral sensitivity to tissue abnormalities in the epithelial layer is thereby improved, whereas orthogonal fibers are more sensitive to the changes in the stromal layer. PMID- 17867817 TI - Ex-vivo spectroscopic quantification of sunscreen efficacy: proposal of a universal sun protection factor. AB - The sun protection factor (SPF) describes the protective behavior of sunscreens insufficiently, because this factor takes into account only the UVB spectral range, and strains the volunteers during its determination by invasively invoking an erythema. A new noninvasive method is proposed that is based on the UV spectroscopic measurement of tape strips taken from a sunscreen-treated skin area. The resulting sum transmission spectra of the tape strips reflect the in vivo distribution of the absorber on the skin and quantify the protective efficacy of the applied sunscreens over the complete UV spectral range. The spectroscopic data provide a basis for the calculation of a universal sun protection factor (USPF). The comparison of the concrete values of USPF and SPF results in the following statements. 1. An unique functional correlation is not to be expected because a different UVB / UVA dependence exists. 2. The size of the differences between both values is influenced clearly by the intensity relation of the average sum transmission in the UVB in comparison to the UVA range. 3. The USPF values objectively assess the efficacy of sunscreens considering a protection against all irradiation injuries. PMID- 17867818 TI - Adaptive filtering for global interference cancellation and real-time recovery of evoked brain activity: a Monte Carlo simulation study. AB - The sensitivity of near-infrared spectroscopy (NIRS) to evoked brain activity is reduced by physiological interference in at least two locations: 1. the superficial scalp and skull layers, and 2. in brain tissue itself. These interferences are generally termed as "global interferences" or "systemic interferences," and arise from cardiac activity, respiration, and other homeostatic processes. We present a novel method for global interference reduction and real-time recovery of evoked brain activity, based on the combination of a multiseparation probe configuration and adaptive filtering. Monte Carlo simulations demonstrate that this method can be effective in reducing the global interference and recovering otherwise obscured evoked brain activity. We also demonstrate that the physiological interference in the superficial layers is the major component of global interference. Thus, a measurement of superficial layer hemodynamics (e.g., using a short source-detector separation) makes a good reference in adaptive interference cancellation. The adaptive-filtering-based algorithm is shown to be resistant to errors in source-detector position information as well as to errors in the differential pathlength factor (DPF). The technique can be performed in real time, an important feature required for applications such as brain activity localization, biofeedback, and potential neuroprosthetic devices. PMID- 17867819 TI - New aspects in assessment of changes in width of subarachnoid space with near infrared transillumination/backscattering sounding, part 1: Monte Carlo numerical modeling. AB - A modified Monte Carlo method was used for numerical modeling of the propagation of near-infrared radiation (NIR) within the anatomical layers of the human head. The distribution of NIR transmission between particular anatomical layers in the measurement region (frontal tubers) of the head was obtained. The study demonstrates the effect of the cardiac pump function-dependent changes in the width of the subarachnoid space (SAS) on the intensity of the backscattered radiation. It was proved that the influence of this factor increases with increasing distance between the observation point and the location of the NIR source placed on the surface of the head. Moreover, with sufficiently small NIR detector-source distance, the contribution of the optic radiation propagated within the SAS to the total signal received is negligibly low, which gives a basis for estimation of the modulatory influence of blood circulation within the superficial skin layer on the total intensity of the backscattered radiation. The dimensions of anatomical layers used in the study are real values measured in a female patient, in whom--due to unique circumstances--it was possible to make measurements followed by recordings in clinical conditions, a situation essential for verification of the results of numerical modeling. PMID- 17867820 TI - New aspects in assessment of changes in width of subarachnoid space with near infrared transillumination-backscattering sounding, part 2: clinical verification in the patient. AB - The study presents comparison of near-infrared light propagation and near infrared backscattered radiation power, as simulated with numerical modeling and measured live in a patient in clinical conditions with the use of the near infrared transillumination-backscattering sounding (NIR-TBSS) technique. A unique chance for such precise comparative analysis was available to us in a clinical case of a female patient with scalp removed from one half of the head due to injury. The analysis performed indicates that the difference between the intensity of the signals in numerical modeling and live measurements is less than 4 dB. Analysis of the theoretical model also provides hints on the positioning of the two detectors relative to the source of radiation. Correctness of these predicted values is confirmed in practical application, when changes of signals received by the detectors are recorded, along with changes of the width of the subarachnoid space. What is more, the power distribution of the spectrum of near infrared backscattered radiation returning to the detectors is confirmed in the real recording in the patient. An abridged description of the new method of NIR TBSS is presented. PMID- 17867821 TI - Investigation of morphometric parameters for granulocytes and lymphocytes as applied to a solution of direct and inverse light-scattering problems. AB - Quantitative data on cell structure, shape, and size distribution are obtained by optical measurement of normal peripheral blood granulocytes and lymphocytes in a cell suspension. The cell nuclei are measured in situ. The distribution laws of the cell and nuclei sizes are estimated. The data gained are synthesized to construct morphometric models of a segmented neutrophilic granulocyte and a lymphocyte. Models of interrelation between the cell and nucleus metric characteristics for granulocyte and lymphocyte are obtained. The discovered interrelation decreases the amount of cell-nucleus size combinations that have to be considered under simulation of cell scattering patterns. It allows faster analysis of light scattering to discriminate cells in a real-time scale. Our morphometric data meet the requirements of scanning flow cytometry dealing with the high rate analysis of cells in suspension. Our findings can be used as input parameters for the solution of the direct and inverse light-scattering problems in scanning flow cytometry, dispensing with a costly and time-consuming immunophenotyping of the cells, as well as in turbidimetry and nephelometry. The cell models developed can ensure better interpretations of scattering patterns for an improvement of discriminating capabilities of immunophenotyping-free scanning flow cytometry. PMID- 17867822 TI - Double-pass versus aberrometric modulation transfer function in green light. AB - Intraocular scattering can become an important source of optical degradation in the aging eye. To evaluate its relative contribution to the ocular modulation transfer function (MTF), a compact, dual experimental system comprising a laser ray tracing (LRT) wavefront sensor and a double-pass setup is used. An aberrometric MTF is estimated from aberration measurements, whereas a second MTF is derived from the double-pass point-spread function. While the former only accounts for the effect of aberrations (up to seventh order), the double-pass MTF includes the combined effect of both scattering and aberrations. A 532-nm laser light source is used to minimize choroidal scattering. Measurements are done on 19 normal, healthy eyes from three groups of subjects of different ages. The two MTFs are obtained for a 6-mm pupil diameter and partial refractive compensation. Intraocular scattering is modeled as a random wavefront aberration characterized by its variance and correlation length. These parameters are fitted from the differences between both MTFs. Our results show that double-pass and LRT techniques provide similar MTFs for most normal eyes, although small amounts of scattering, or high-order aberrations, could be measured in some eyes. A gradual increase in intraocular scattering with age is also observed. PMID- 17867823 TI - Three-dimensional panoramic imaging of cardiac arrhythmias in rabbit heart. AB - Cardiac fluorescent optical imaging provides the unique opportunity to investigate the dynamics of propagating electrical waves during ventricular arrhythmias and the termination of arrhythmias by strong electric shocks. Panoramic imaging systems using charge-coupled device (CCD) cameras as the photodetector have been developed to overcome the inability to monitor electrical activity from the entire cardiac surface. Photodiode arrays (PDAs) are known to have higher temporal resolution and signal quality, but lower spatial resolution compared to CCD cameras. We construct a panoramic imaging system with three PDAs and image Langendorff perfused rabbit hearts (n=18) during normal sinus rhythm, epicardial pacing, and arrhythmias. The recorded spatiotemporal dynamics of electrical activity is texture mapped onto a reconstructed 3-D geometrical heart model specific to each heart studied. The PDA-based system provides sufficient spatial resolution (1.72 mm without interpolation) for the study of wavefront propagation in the rabbit heart. The reconstructed 3-D electrical activity provides us with a powerful tool to investigate the fundamental mechanisms of arrhythmia maintenance and termination. PMID- 17867824 TI - Indocyanine-green-embedded PEBBLEs as a contrast agent for photoacoustic imaging. AB - Nanoparticles 100 nm in diameter containing indocyanine green (ICG) have been developed as a contrast agent for photoacoustic (PA) imaging based on (photonic explorers for biomedical use by biologically localized embedding PEBBLE) technology using organically modified silicate (ormosil) as a matrix. ICG is an FDA-approved dye with strong optical absorption in the near-infrared (NIR) region, where light can penetrate deepest into biological tissue. A photoacoustic imaging system was used to study image contrast as a function of PEBBLE concentration in phantom objects. ICG-embedded ormosil PEBBLEs showed improved stability in aqueous solution compared with free ICG dye. The particles were conjugated with HER-2 antibody for breast cancer and prostate cancer cell targeting. Initial in vitro characterization shows high contrast and high efficiency for binding to prostate cancer cells. ICG can also be used as a photosensitizer (generating toxic oxygen by illumination) for photodynamic therapy. We have measured the photosensitization capability of ICG-embedded ormosil nanoparticles. This feature can be utilized to combine detection and therapeutic functions in a single agent. PMID- 17867825 TI - Receptor-targeted quantum dots: fluorescent probes for brain tumor diagnosis. AB - The intraoperative diagnosis of brain tumors and the timely evaluation of biomarkers that can guide therapy are hindered by the paucity of rapid adjunctive studies. This study evaluates the feasibility and specificity of using quantum dot-labeled antibodies for rapid visualization of epidermal growth factor receptor (EGFR) expression in human brain tumor cells and in surgical frozen section slides of glioma tissue. Streptavidin-coated quantum dots (QDs) were conjugated to anti-EGFR antibodies and incubated with target cultured tumor cells and tissues. The experiments were conducted first in human glioma tumor cell lines with elevated levels of EGFR expression (SKMG-3, U87) and then in frozen tissue sections of glioblastoma multiforme and of oligodendroglioma. The bioconjugated QDs used in the study were found to bind selectively to brain tumor cells expressing EGFR. QD complexed quickly to the cell membrane (less than 15 min), and binding was highly specific and depended on the expression level of EGFR on the cell membrane. Tissue experiments showed that only tumor specimens expressing EGFR were labeled in less than 30 min by QD complexes. These findings demonstrate that QD-labeled antibodies can provide a quick and accurate method for characterizing the presence or absence of a specific predictive biomarker. PMID- 17867826 TI - High-resolution photonic bandgap fiber-based biochemical sensor. AB - The use of photonic bandgap fibers (PBGF) for biomedical sensing has been demonstrated. The demonstrated PBGF has a blue wavelength shift of 280 nm in the falling photonic bandgap edge (PBE) when the ambient refractive indices inside the holey region change from 1.333 to 1.39, which agrees well with the analytical prediction. Combining this with the knowledge of immobilization techniques and biorecognition elements could open up a new class of PBGF-based label-free biosensors. A sensitivity on the order of 0.1 nmol/L could be achieved by consuming less than 1 microL of sample. PMID- 17867827 TI - Sensitive biosensor array using surface plasmon resonance on metallic nanoslits. AB - Chip-based biosensor arrays for label-free and high-throughput detection were fabricated and tested. The sensor array was composed of a 150-nm-thick, 50-nm gap, and 600-nm-period gold nanoslits. Each array size was 100 mumx100 mum. A transverse-magnetic polarized wave in these metallic nanostructures generated resonant surface plasmons at a wavelength of about 800 nm in a water environment. Using the resonant wavelength shift in the nanoslit array, we achieved detection sensitivity up to 668 nm per refractive index unit, about 1.7 times larger than that reported on an array of nanoholes. An antigen-antibody interaction experiment in an aqueous environment verified the sensitivity in a surface binding event. PMID- 17867828 TI - Prevalence and population structure of lice (Phthiraptera) on the Indian Red Avadavat. AB - Prevalences of two phthirapteran species (an ischnoceran, Brueelia amandavae, and an amblyceran, Myrsidea amandava) on 130 Red Avadavats (Amandava amandava) were 36.2 and 20.8% in the district of Rampur, India, from September to December 2004. Sample mean abundances of the two species were 3.43 and 1.53, respectively. The frequency distribution patterns of both species were aggregated. The observed distribution conformed to the expected distribution of the negative binomial model, but only in the case of M. amandava. Adults dominated over nymphs in the overall adult-to-nymph ratio. Sex ratios of both species were skewed (female biased). PMID- 17867829 TI - A taxonomic catalogue of Japanese nemerteans (phylum Nemertea). AB - A literature-based taxonomic catalogue of the nemertean species (Phylum Nemertea) reported from Japanese waters is provided, listing 19 families, 45 genera, and 120 species as valid. Applications of the following species names to forms previously recorded from Japanese waters are regarded as uncertain: Amphiporus cervicalis, Amphiporus depressus, Amphiporus lactifloreus, Cephalothrix filiformis, Cephalothrix linearis, Cerebratulus fuscus, Lineus vegetus, Lineus bilineatus, Lineus gesserensis, Lineus grubei, Lineus longifissus, Lineus mcintoshii, Nipponnemertes pulchra, Oerstedia venusta, Prostoma graecense, and Prostoma grande. The identities of the taxa referred to by the following four nominal species require clarification through future investigations: Cosmocephala japonica, Dicelis rubra, Dichilus obscurus, and Nareda serpentina. The nominal species established from Japanese waters are tabulated. In addition, a brief history of taxonomic research on Japanese nemerteans is reviewed. PMID- 17867830 TI - Population expansion of the poultry fluff louse, Goniocotes gallinae (De Geer, 1778) (Ischnocera, Phthiraptera). AB - A study was undertaken to determine the rate of population expansion of an ischnoceran Phthiraptera, Goniocotes gallinae (infesting the domestic fowl, Gallus gallus domesticus), on the basis of in vitro and in vivo studies. Data obtained from in vitro rearing were utilized to construct the life history of the louse. The values of the gross reproductive rate (12.49 female eggs/female), net reproductive rate (8.31 female eggs/female), mean length of generation (36.91 days), precise generation time (35.65 days), finite rate of increase (1.06 female/days), and intrinsic rate of natural increase (0.059) of G. gallinae were determined. However, doubling-time values recorded during in vivo studies (14 days) was comparatively higher than those during in vitro rearing (11.73 days). PMID- 17867831 TI - Sensitive period in which walking affects recovery of direction of wind-evoked escape in the cricket Gryllus bimaculatus. AB - Unilaterally cercus-ablated crickets, Gryllus bimaculatus, were reared in an apparatus that induced walking artificially. In the crickets that experienced different distances of enforced walking per day, the directionality of escape was investigated before and 1, 4, 7, 10, 13, and 16 days after the ablation of the cercus. The crickets that walked a longer distance per day showed a quicker and a higher degree of compensational recovery of the escape direction than the crickets that walked a shorter distance per day, even after walking the same distance. Thus, the time course and amount of compensational recovery from cercal ablation depend on when crickets experience walking during the recovery period. During the recovery period, unilaterally cercus-ablated crickets were subjected to walking at different times to determine the most effective period in which walking affects the compensational recovery of escape direction. The compensational recovery of the escape direction occurred only in crickets experiencing walking in early periods after the ablation. In particular, walking experienced 2-6 days after the ablation was most effective for the compensational recovery. On the other hand, no compensational recovery occurred in crickets experiencing walking in later periods after the ablation. These results suggest that there is a sensitive or critical period in which walking affects the compensational recovery of escape direction. PMID- 17867832 TI - Excess tyrosine restores the morphology and maturation of melanosomes affected by the murine slaty mutation. AB - The slaty (Dct(slt)) mutation is known to reduce the activity of dopachrome tautomerase in melanocytes and to reduce the melanin content in the skin, hairs, and eyes. The slaty gene is known to be important for maximizing melanin deposition in melanosomes. However, it was not known whether the slaty mutation affects the morphology of melanosomes. Moreover, it was unknown whether melanosome development is modulated by melanogenic factors. In this study, the characteristics of melanosomes of slaty melanocytes in serum-free primary culture were investigated in detail under the electron microscope. In slaty melanocytes, melanosome maturation was blocked at stage III, and numerous spherical melanosomes with globular depositions of pigment in addition to elliptical melanosomes were observed. L-tyrosine (Tyr), the starting material of melanin synthesis, is known to stimulate melanin synthesis. To clarify whether L-Tyr restores the reduced production of melanin, L-Tyr was added to the culture medium and tested for its melanogenic effect. L-Tyr greatly increased the number and percentage of mature stage IV melanosomes. Moreover, L-Tyr increased elliptical melanosomes, but decreased spherical melanosomes. These results suggest that the slaty mutation inhibits the development of elliptical stage IV melanosomes, and that L-Tyr restores the development of elliptical stage IV melanosomes. L-Tyr seems to restore both the morphology and maturation of melanosomes affected by the slaty mutation. PMID- 17867833 TI - Molecular evidence suggesting interspecific hybridization in Zoanthus spp. (Anthozoa: Hexacorallia). AB - Interspecific hybridization has been proposed as a possible explanation for the incredible diversity seen in reef-dwelling corals, but until now little proof of such hybridization in other reef-dwelling anthozoans has been reported. Without further observation of hybridization, the question of such a phenomenon being widespread in Anthozoa remains. Here we have examined the mitochondrial cytochrome oxidase I gene (COI) and the nuclear internal transcribed spacer of ribosomal DNA (ITS-rDNA) from three species of the mass-spawning, encrusting anemone genus Zoanthus (Z. sansibaricus, Z. kuroshio, Z. gigantus) to investigate possible hybridization. The three species coexist at two of three sampling locations in southern Japan. Zoanthus spp. ITS-rDNA region spacers (ITS-1 and ITS 2) were shown to have very high rates of divergence. At locations where all three species co-existed, several of our sampled Z. sansibaricus individuals (with identical "sansi" COI sequences) possessed two very divergent (i.e., species level difference) ITS-rDNA alleles, the expected "sansi" allele and the divergent "B" allele. Additionally, two Z. sansibaricus individuals possessed only "B" alleles despite having "sansi" COI sequences. These results indicate that Z. sansibaricus has possibly experienced interspecific hybridization at least once with a Zoanthus partner possessing the "B" allele, and that these resulting hybrids may also sexually reproduce, demonstrating potential hybridization occurring in the order Zoantharia (Hexacorallia). PMID- 17867834 TI - Genetic relationships and reproductive-isolation mechanisms among the Fejervarya limnocharis complex from Indonesia (Java) and other Asian countries. AB - In order to elucidate the genetic relationships and reproductive-isolation mechanisms among the Fejervarya limnocharis complex from Indonesia and other Asian countries, allozyme analyses and crossing experiments were carried out using 208 individuals from 21 localities in eight Asian countries. The allozyme analyses revealed that 17 enzymes examined were controlled by genes at 27 loci, and that 7.9 phenotypes were produced by 5.2 alleles on average. The two species recognized in F. limnocharis sensu lato from Southeast Asia (i.e., F. limnocharis sensu stricto and F. iskandari) were found to occur sympatrically at three localities (Bogor, Cianjur and Malingping), all on Java, Indonesia. Fejervaya iskandari was dominant at each of these localities and showed substantial geographic genetic variation. Laboratory-produced hybrids between F. limnocharis and F. iskandari from Java became underdeveloped and died at the tadpole stage, suggesting that these species are completely isolated by hybrid inviability. Hybrids between topotypic F. limnocharis and the Malaysian and Japanese conspecific populations developed normally to metamorphosis. Likewise, hybrids between topotypic F. iskandari and the Thailand and Bangladesh conspecific populations also showed normal viability throughout larval development. The present allozyme analyses and crossing experiments strongly suggested the presence of two distinct forms, the large type and the small type, in the F. limnocharis complex from Asia, and further subdivision of the large type into the F. limnocharis assemblage and the F. iskandari assemblage. The small type was found in samples from India, Thailand, Bangladesh and Sri Lanka, and included at least three different species. The sample from Pilok, Thailand, was considered to represent an undescribed species. PMID- 17867835 TI - An assessment of initial body size in loggerhead sea turtle (Caretta caretta) hatchlings in Turkey. AB - Eggs, hatchlings, and adult loggerhead turtles, and incubation durations of clutches, were measured on three Turkish beaches (Dalyan, Fethiye and Goksu Delta), and some physical features of nests were compared. These features were not statistically different among the beaches, except for nest depth and distance to the high water mark. There was a positive relationship between hatchling mass and egg size. The carapace length of hatchlings was correlated with both egg diameter and incubation duration. The duration of asynchronous emergence of hatchlings on Fethiye beach was slightly longer than on the other two beaches, and the size of hatchlings decreased as asynchronous emergence proceeded. Of the hatchlings that emerged first, those that died were significantly smaller in SCL and mass than those that lived. These results suggest that smaller hatchlings may not be vigorous enough to emerge earlier from nests, and that they may be less fit. PMID- 17867836 TI - Phenotypic responses of hatchlings to constant versus fluctuating incubation temperatures in the multi-banded krait, Bungarus multicintus (Elapidae). AB - Most studies on egg incubation in reptiles have relied on constant temperature incubation in the laboratory rather than on simulations of thermal regimes in natural nests. The thermal effects on embryos in constant-temperature studies often do not realistically reflect what occurs in nature. Recent studies have increasingly recognized the importance of simulating natural nest temperatures rather than applying constant-temperature regimes. We incubated Bungarus multicintus eggs under three constant and one fluctuating-temperature regimes to evaluate the effects of constant versus fluctuating incubation temperatures on hatching success and hatchling phenotypes. Hatching success did not differ among the four treatments, and incubation temperature did not affect the sexual phenotype of hatchlings. Incubation length decreased as incubation temperature increased, but eggs incubated at fluctuating temperatures did not differ from eggs incubated at constant temperatures with approximately the same mean in incubation length. Of the hatchling phenotypes examined, residual yolk, fat bodies and locomotor performance were more likely affected by incubation temperature. The maximal locomotor speed was fastest in the fluctuating temperature and 30 degrees C treatments and slowest in the 24 degrees C treatment, with the 27 degrees C treatment in between. The maximal locomotor length was longest in the fluctuating-temperature treatment and shortest in the 24 degrees C and 27 degrees C treatments, with the 30 degrees C treatment in between. Our results show that fluctuating incubation temperatures do not influence hatching success and hatchling size and morphology any differently than constant temperatures with approximately the same mean, but have a positive effect on locomotor performance of hatchlings. PMID- 17867837 TI - Effects of homologous ghrelins on the growth hormone/insulin-like growth factor-I axis in the tilapia, Oreochromis mossambicus. AB - Ghrelin is a gut-brain peptide synthesized mainly in the oxyntic mucosal cells of the stomach, and has potent growth hormone (GH)-releasing and orexigenic activities. Recently, two forms of ghrelin, ghrelin-C8 and -C10, were identified in the Mozambique tilapia (Oreochromis mossambicus). The present study describes in vitro and in vivo effects of these endogenous ghrelins on the GH/insulin-like growth factor-I (IGF-I) axis. Ghrelin-C8 (100 nM) stimulated GH release from primary cultures of pituitary cells after 4 and 8 h of incubation, whereas no effect was seen on prolactin (PRL) release. Stimulatory effects of ghrelin-C8 and -C10 (100 nM) on GH release during 6 h of incubation were blocked by pre incubation with GHS receptor antagonist, [D-Lys(3)]-GHRP-6 (10 microM). Intraperitoneal injection of ghrelin-C8 (1 ng/g body weight) and -C10 (0.1 and 1 ng/g body weight) significantly increased plasma GH levels after 5 h. Significant increases were observed also in hepatic expression of IGF-I and GH receptor (GHR) mRNA following injections of both forms of ghrelin (0.1 and 1 ng/g body weight), although there was no effect on plasma levels of IGF-I. In the next experiment, both forms of ghrelin (1 ng/g body weight) significantly increased plasma IGF-I levels 10 h after the injection. No significant effect of either ghrelin was observed on plasma PRL levels. Both forms of GHS receptor (GHSR-1a and -1b) were found in the pituitary, clearly indicating that tilapia ghrelins stimulate primarily GH release through the GHS receptor. Stimulation of hepatic expression of IGF-I and GHR suggests metabolic roles of ghrelin in tilapia. PMID- 17867838 TI - Construction and characterization of a Lipotes vexillifer genomic DNA BAC library. AB - We constructed a genomic DNA library for Lipotes vexillifer (L. vexillifer), the Baiji or Yangtze River dolphin, one of the most endangered mammals in the world. The library consists of 149,000 BAC clones, with an average insert size of 83 kb, representing approximately 3.4 haploid genome equivalents. PCR amplification of four known L. vexillifer genes yielded two to four positive clones each. To demonstrate the utility of this library, we isolated and sequenced the L. vexillifer alpha lactalbumin gene, which is a gene specific to mammals and one which has been widely used as molecular tool in phylogenetic analysis. We also end-sequenced 20 randomly selected clones, resulting in the identification of at least five new L. vexillifer genes, five SSR loci, and one SINE locus. These results suggest that this library is a valuable resource for candidate gene cloning, physical mapping, and genome sequencing of this important and threatened species. PMID- 17867839 TI - Highly sensitive second-antibody enzyme immunoassay for determination of estradiol-17beta concentration in blood plasma of the mithun (Bos frontalis). AB - The objective of the present study was to develop and validate a simple, sensitive, quick and economic enzyme immunoassay (EIA) for estradiol-17beta (E2) in mithun (Bos frontalis) plasma on microtiter plates using a second-antibody coating technique and hormone-horseradish peroxidase as a label. For the assay, the wells of microtiter plates were coated with affinity-purified goat anti rabbit IgG that binds the hormone-specific antibody. One milliliter of mithun plasma was extracted using benzene and 50 microl of 300 microl volume reconstituted with assay buffer was run in the assay along with standards ranging from 0.10-100 pg/well prepared in assay buffer. The sensitivity of the assay was 0.72 pg/ml. The intra- and inter-assay coefficients of variation were below 10%, and the extraction efficiency was >93%. Linearity of recovery of the added hormone concentrations was recorded. The assay developed was further validated biologically by estimating the hormone concentrations in six female and five male mithun calves, 12 cyclic mithuns for the entire reproductive cycle, and four pregnant mithun cows. The EIA developed can estimate low concentrations of E2 (2.2-5.2 pg/ml) in growing calves as well as very high concentrations of the hormone during pregnancy (E2=85.6-143.5 pg/ml). Apart from being non-radioactive, the assay developed has several advantages over conventional radioimmunoassays: it is more sensitive, less labor intensive, simpler to perform, and less time consuming. In conclusion, the EIA procedure described herein is sufficiently reliable, economic, safe, quick and sensitive to estimate the hormone at all physiological levels in bovine plasma. PMID- 17867840 TI - The Oriental 'fly-like' leafhoppers of the subfamily Stegelytrinae - the Doda group (Hemiptera: Cicadellidae). AB - The Oriental 'fly-like' leafhoppers of the Doda group are reviewed and a key is given for their separation. Two new genera and two new species are described: Pseudododa gen. n. (with type species P. orientalis sp. n.) and Aculescutellaris gen. n. (with type species A. hirtellus sp. n.). The variation within the former species is documented and illustrated, and the special mineral uptake behavior ('mud-puddling') of this genus and other Cicadellidae is reviewed. PMID- 17867841 TI - Discrimination of individuals by odor in male Mongolian gerbils, Meriones unguiculatus. AB - The ability to discriminate among individuals plays a fundamental role in the establishment of social relationships in animals. We examined how Mongolian gerbils (Meriones unguiculatus) discriminate among individuals using odor. In the first experiment, the ability of male gerbils to discriminate among five odor sources from different individuals was investigated using a habituation dishabituation paradigm. After male gerbils had been habituated to a scent from one individual, they were exposed to familiar and unfamiliar scents from different donors simultaneously. Where urine and ventral gland secretions were used, the subjects spent more time investigating novel odors than familiar ones, suggesting that they were able to discriminate individual differences in these odor sources. However, with the scents of feces and saliva, they could detect, but could not discriminate individual differences; with scent from inside the pinnae, they could not even detect. In the second experiment, we tested whether cross-habituation occurred between the scents of urine and ventral gland secretions. A male was exposed repeatedly to urine from one of two familiar donor males during four habituation trials, and was then exposed to the ventral gland secretions from two donors simultaneously. The subject males spent more time investigating scents of ventral gland secretions, but there was no difference in the investigation time between ventral gland scents from the two donors. These results suggest that male gerbils discriminate among individuals using odors from urine and ventral gland secretions and that cross-habituation may not occur between these scents during social-memory formation. PMID- 17867842 TI - The ecology of male egg attendance in an arboreal breeding frog, Chirixalus eiffingeri (Anura: Rhacophoridae), from Taiwan. AB - Field observations were conducted on egg attendance in Chirixalus eiffingeri from April to August 2003. Parental attendance during embryonic development was performed exclusively by males. The frequency of egg attendance was low (27%), but it had a distinct diel pattern in which males were observed to attend eggs more frequently at night than during the day. Attendance frequency significantly decreased with increasing developmental stage of the embryos, but it was not statistically significantly related to clutch size. Field observations confirmed that male frogs actively moisten egg clutches using their ventral surfaces, presumably to prevent desiccation of egg clutches. The non-significant relationship between hatching success and frequency of egg attendance suggests that embryonic survival of C. eiffingeri is more than a function of egg attendance, and ecological and environmental factors, such as climate and characteristics of microhabitats, may also influence the survivorship of the embryos. PMID- 17867843 TI - Regionalization of the tail-tip epidermis requires inductive influence from vegetal cells and FGF signaling in the development of an ascidian, Halocynthia roretzi. AB - The epidermis of an ascidian larva derived from animal-hemisphere cells is regionalized along the anterior-posterior (AP) axis through inductive signals emanating from vegetal-hemisphere cells in early stages of the development. Previously, we showed by blastomere isolation and ablation experiments that the contact between the animal and vegetal hemispheres until the 32-cell stage is necessary for the proper AP patterning of the epidermis in the tailbud-stage embryo. We here addressed the patterning mechanism of the posteriormost epidermis using a tail-tip epidermis marker, HrTT-1. Employing blastomere isolation and ablation experiments along with knockdown of a master regulator gene for posterior mesoderm, we have demonstrated that presence of the posterior vegetal cells after the 32-cell stage is necessary for the expression of HrTT-1. To explore the timing and nature of the influence of the posterior vegetal cells, we treated the embryos with FGF signaling inhibitors at various developmental stages and found that HrTT-1 expression was lost from embryos treated with the inhibitors from stages earlier than the late neurula stage, just prior to the onset of HrTT-1 expression but not after the initial tailbud stage, at which the expression of HrTT-1 had started. In embryos lacking HrTT-1 expression, the expression domain of Hrcad, which would otherwise be localized anterior to that of HrTT-1, expanded to the tail-tip. These results suggest that FGF signaling from the neurula to initial tailbud stages is necessary for the initiation but not maintenance of HrTT-1 expression in the tail-tip epidermis. The contact with posterior vegetal cells until and after the 32-cell stage may be required for FGF signaling to occur in the posterior tail, which in turn regionalizes the tail-tip epidermal territory. PMID- 17867844 TI - Sequence variation in the Tbx4 gene in marine mammals. AB - The amino-acid sequences of the T-domain region of the Tbx4 gene, which is required for hindlimb development, are 100% identical in humans and mice. Cetaceans have lost most of their hindlimb structure, although hindlimb buds are present in very early cetacean embryos. To examine whether the Tbx4 gene has the same function in cetaceans as in other mammals, we analyzed Tbx4 sequences from cetaceans, dugong, artiodactyls and marine carnivores. A total of 39 primers were designed using human and dog Tbx4 nucleotide sequences. Exons 3, 4, 5, 6, 7, and 8 of the Tbx4 genes from cetaceans, artiodactyls, and marine carnivores were sequenced. Non-synonymous substitution sites were detected in the T-domain regions from some cetacean species, but were not detected in those from artiodactyls, the dugong, or the carnivores. The C-terminal regions contained a number of non-synonymous substitutions. Although some indels were present, they were in groups of three nucleotides and therefore did not cause frame shifts. The dN/dS values for the T-domain and C-terminal regions of the cetacean and artiodactylous Tbx4 genes were much lower than 1, indicating that the Tbx4 gene maintains it function in cetaceans, although full expression leading to hindlimb development is suppressed. PMID- 17867845 TI - Phylogeography and introgressive hybridization of the ground beetle Carabus yamato in Japan based on mitochondrial gene sequences. AB - To study the phylogeography of the ground beetle Carabus yamato in Japan, we compared 1,020-bp sequences of the mitochondrial NADH dehydrogenase subunit 5 (ND5) gene from 373 specimens from 37 localities with those of three parapatric species (C. albrechti, C. kimurai, and C. japonicus) that might share mitochondrial lineages with C. yamato through introgressive hybridization. We found 81 haplotypes from C. yamato. Of these, 17 haplotypes were considered to be of an introgressed lineage from C. albrechti, based on the phylogeny and geographic distribution. In addition, one haplotype of C. kimurai was likely an introgressant from C. yamato. Putative introgression events among the four species were restricted to these two directional cases. We analyzed the phylogeography of C. yamato using nested clade phylogeographical analysis and population genetic parameters. The mitochondrial lineages of C. yamato were estimated to have diverged no more than approximately 1.12 million years ago, implying that the estimated historical events occurred after the Early Pleistocene. Carabus yamato was inferred to have experienced a contraction of its distribution range, followed by recent range expansion. Populations in the western and eastern regions, segregated by Ise Bay and the Nobi and Okazaki Plains, diverged in the mitochondrial clades. The northern and most western populations possessed one clade only (except an introgressed lineage), whereas eastern and some southwestern populations possessed several diverged clades, which were considered to be ancestral; these populations may have been associated with refugia during glacial periods. PMID- 17867846 TI - Geographical divergence in the Japanese land snail Euhadra herklotsi inferred from its molecular phylogeny and genital characters. AB - We studied genetic variation within the Japanese land snail Euhadra herklotsi, which occurs on Kyushu and the surrounding islands, using partial sequences of the mitochondrial COI gene and nuclear ITS2 genes. The phylogenetic analysis revealed the existence of two major clades: clade N in the north and clade S in the south. These clades were parapatric and overlapped in southern Kyushu. Genetic divergence was high in clade N, whereas it was much lower in clade S. In addition, isolation-by-distance within each clade was implied. Since no current geographical barriers separate these clades, the genetic structure of clade S might have been influenced by historical events, such as volcanic activity, and a resulting population bottleneck followed by range expansion. The genital characteristics of clade-S snails were distinct from those of clade-N snails, and snails in both clades were sympatric at one locality. The shells of clade-N snails were generally larger than those of clade-S snails, but the shell-size variation within each clade could not be explained simply by environmental variables. Our study suggests that E. herklotsi likely consists of two sibling species. The taxonomic status of the previously proposed subspecies of E. herklotsi and related species requires reassessment. PMID- 17867847 TI - Inheritance pattern of lateral dimorphism in two cichlids (a scale eater, Perissodus microlepis, and an herbivore, Neolamprologus moorii) in Lake Tanganyika. AB - Antisymmetry in the direction of the mouth opening, to either the right ("lefty") or left ("righty"), was documented in the scale-eating cichlid Perissodus microlepis. This study revealed the presence of lefty and righty mouth morphs in the herbivorous cichlid Neolamprologus moorii, although the degree of deviation was not large. Both species are biparental brooders and guard their young. We examined the inheritance pattern of the dimorphism (laterality) using parents and broods of P. microlepis and N. moorii collected in the wild. In P. microlepis, lefty-lefty pairs had a 2:1 frequency of lefty:righty young, lefty-righty pairs a similar number of each type of young, and righty-righty pairs only righty young. Similar inheritance patterns were observed in N. moorii. We propose two hypotheses to explain the inheritance pattern: Mendelian genetics with the lefty allele dominant over the righty and the dominant allele homozygous lethal, and cross-incompatibility that is predominant in lefty homozygotes. PMID- 17867848 TI - A rapid sex-identification test for the forest musk deer (Moschus berezovskii) based on the ZFX/ZFY gene. AB - We describe a rapid sex-identification method for the forest musk deer (Moschus berezovskii) using PCR based on zinc-finger protein-encoding genes (ZFX/ZFY) located on the X and Y chromosomes. Fragments of the ZFX and ZFY genes were amplified and sequenced. The ZFX and ZFY fragments were identical in length and 94% similar in nucleotide sequence. Specific primers for forest musk deer sex identification were designed on the basis of sequence differences between ZFX and ZFY. All the primers were multiplexed in single-tube PCR. Both male and female forest musk deer showed amplification bands of 447 bp and 212 bp separated in agarose gels. A sex-specific 278-bp band was amplified only from males. These results show that testing by PCR for the presence of the 278-bp sequence is a rapid and reliable method for sex identification. PMID- 17867849 TI - Description of male Takydromus sylvaticus (Squamata: Lacertidae) from China, with notes on sexual dimorphism and a revision of the morphological diagnosis of the species. AB - The Chungan ground lizard, Takydromus sylvaticus, long known only from five females collected in Fujian Province of China, was recently found in Anhui Province of the country. The newly collected specimens included the first male specimens (n=7), in which the tail bases were stouter than in conspecific females. Ventral scales in these males were invariably keeled, whereas in females those forming the four median rows were smooth. Females had more dorsal scales (47-48) than males (42-43) in the median longitudinal row between axilla and groin. Takydromus sylvaticus differed from the closely related T. dorsalis in having more dorsal scales in the median longitudinal row between axilla and groin (42-48 versus 32-40, respectively), more rows of large dorsal scales between the hind legs (10 versus 7-8, respectively), shorter hind legs, two distinct white longitudinal stripes on each side of the body, and no black stripe in the preocular and postocular regions. The number of transverse rows of ventral scales between collar and femoral pores in T. sylvaticus (26-28) was larger, but with a slight overlap, than that in T. dorsalis (22-26). Ecological observations on T. sylvaticus were also documented. PMID- 17867850 TI - Identification of common excitatory motoneurons in Drosophila melanogaster larvae. AB - In insects, four types of motoneurons have long been known, including fast motoneurons, slow motoneurons, common inhibitory motoneurons, and DUM neurons. They innervate the same muscle and control its contraction together. Recent studies in Drosophila have suggested the existence of another type of motoneuron, the common excitatory motoneuron. Here, we found that shakB-GAL4 produced by labels this type of motoneuron in Drosophila larvae. We found that Drosophila larvae have two common excitatory motoneurons in each abdominal segment, RP2 for dorsal muscles and MNSNb/d-Is for ventral muscles. They innervate most of the internal longitudinal or oblique muscles on the dorsal or ventral body wall with type-Is terminals and use glutamate as a transmitter. Electrophysiological recording indicated that stimulation of the RP2 axon evoked excitatory junctional potential in a dorsal muscle. PMID- 17867851 TI - Laboratory culture of the Oriental lancelet Branchiostoma belcheri. AB - To overcome difficulties in getting research materials of cephalochordate lancelets, which has severely hampered experimental studies of this animal, we have attempted to establish a culture system in the laboratory. Adult animals collected from the wild were maintained in 2.5-L plastic containers filled with natural seawater without sand substratum. They were fed daily with unicellular algae. About 25% of the animals collected in 2003, 2004, and 2005 developed gonads in our culture system. Some of the sexually mature animals collected in the breeding seasons in 2005 and 2006 spawned spontaneously in the plastic containers of this system. Broods obtained in 2005 were maintained longer than a year in a glass tank without sand substratum. The progeny born in the laboratory showed great individual variation in growth but metamorphosed normally, and some of them started to develop gonads around 10 months after fertilization. Our mass culture methods for both adults and their progeny made daily observation possible and allowed the constant spawning of animals collected from the wild, at least in the summer season. Our culture method saves labor in maintenance and is easily set up without any specific demands except for running seawater, though still required to better survival rate and spawning control. Lancelet populations maintained in the laboratory can promote studies on these animals across disciplines and especially contribute to elucidation of the evolutionary history of chordates. PMID- 17867852 TI - Evidence for processing enzymes in the abdominal gland of the newt, Cynops pyrrhogaster, that generate sodefrin from its biosynthetic precursor. AB - Sodefrin (Ser-Ile-Pro-Ser-Lys-Asp-Ala-Leu-Leu-Lys) is a female-attracting peptide pheromone secreted by the abdominal gland of the male red-bellied newt, Cynops pyrrhogaster. Sequence analysis of a cDNA encoding sodefrin revealed that the peptide is located in the C-terminal region of its precursor protein (residues 177-186 of preprosodefrin) and extended from its C-terminus by the tripeptide sequence Ile(187)-Ser(188)-Ala(189) and flanked at its N-terminus by Leu(174) Gly(175)-Arg(176). This suggests that sodefrin is generated by enzymatic cleavage at monobasic (Lys and Arg) sites within the precursor molecule. To demonstrate the presence in the abdominal gland of proteolytic enzymes capable of generating sodefrin, an enzymatic assay was developed using t-butoxycarbo-nyl (Boc)-Leu-Gly Arg-4methylcoumaryl-7-amide (MCA) and Boc-Leu-Leu-Lys-MCA as synthetic substrates. A crude extract of the abdominal gland hydrolyzed both substrates to liberate 7-amino-4- methylcoumarin, suggesting that enzymes that generate sodefrin from its precursor molecule are present in the gland. The activity in the extract for cleaving Boc-Leu-Gly-Arg-MCA was optimal at pH 9.0 and 45 degrees C and for Boc-Leu-Leu-Lys-MCA at pH 9.0 and 40 degrees C. The effects of a range of specific inhibitors on activities in the extract suggest an involvement of enzymes belonging to the serine protease family. It was also demonstrated that enzymatic activity in an extract of the abdominal glands of sexually developed males was significantly (three- to six-fold; p<0.01) higher than that of sexually undeveloped males. PMID- 17867853 TI - A new frog species from the central western Ghats of India, and its phylogenetic position. AB - Tropical evergreen forests of Indian subcontinent, especially of the Western Ghats, are known hot spots of amphibian diversity, where many new anuran species await to be identified. Here we describe from the Sharavathi River basin of central Western Ghats a new shrub-frog taxon related to the anuran family Rhacophoridae. The new frog possesses the characteristic features of rhacophorids (dilated digit tips with differentiated pads circumscribed by a complete groove, intercalary cartilages on digits, T-shaped terminal phalanges and granular belly, the adaptive characters for arboreal life forms), but also a suite of unique features that distinguish it from all known congeners in the region. Morphogenetic analysis based on morphological characteristics and diversity in the mitochondrial 12S and 16S rRNA genes revealed it to be a new Philautus species that we named Philautus neelanethrus sp. nov. The phylogenetic analysis suggests the new frog to represent a relatively early Philautus species lineage recorded from the region. The distribution pattern of the species suggests its importance as a bioindicator of habitat health. In general, this relatively widespread species was found distributed only in non-overlapping small stretches, which indirectly indicates the fragmentation of the evergreen to moist deciduous forests that characterize the Western Ghats. Thus the discovery of the new rhacophorid species described here not only further reinforces the significance of the Western Ghats as a major hotspot of amphibian biodiversity, but also brings into focus the deterioration of forest habitats in the region and the need for prioritization of their conservation. PMID- 17867854 TI - Round-the-clock homing behavior of a subsocial shield bug, Parastrachia japonensis (Heteroptera: Parastrachiidae), using path integration. AB - Females of the subsocial shield bug, Parastrachia japonensis (Parastrachiidae), are central-place foragers, collecting drupes for their young from nearby host trees by walking along the forest floor both during the day and at night. Because burrows are often some distance from the drupe-shedding tree, the bugs must repeatedly leave their burrows, search for drupes, and return to the burrows. After a bug leaves its burrow, it searches arduously until it encounters a drupe. When a drupe is obtained, the bug always takes the shortest route back to its burrow. It has been clarified that this bug utilizes path integration during diurnal provisioning excursions. In this paper, we examined nocturnal behavior and some parameters of the path integration utilized by P. japonensis. There were no observable differences between day and night in the patterns of foraging and direct-homing behavior. When the bug was displaced to another position during the day or night, it always walked straight toward the fictive burrow, the site where the burrow should be if it had been displaced along with the bug, and then displayed searching behavior in the vicinity of the fictive burrow. The distance of the straight run corresponded accurately with a straight line between the burrow and the place where the bug obtained the drupe. These results indicate that P. japonensis orients toward the burrow using path integration both during diurnal and nocturnal provisioning behavior. PMID- 17867855 TI - Body muscle-cell differentiation from coelomic stem cells in colonial tunicates. AB - Body muscle-cell differentiation was ultrastructurally examined in palleal buds of the colonial tunicate Symplegma reptans. Undifferentiated coelomic cells accumulate near the primordial oral siphon and associate with the basal lamina beneath the epidermis. They initially display the characteristics of hemoblast cells that have a large nucleus with a prominent nucleolus and narrow cytoplasm filled with polysomes. However, they soon become unique due to the development of an indented contour of the nucleus. When the basal lamina of the epidermis develops into the fibrous extracellular matrix (ECM), the muscle precursor cell has the deeply-notched nucleus, and thick and thin filaments in the cytoplasm facing the ECM. Collagen fibril-like structures appear in the ECM. Myofilaments are arranged with the ratio of thick to thin filaments being 1:2.5. Dense bodies and plaques become evident before the oral siphon is perforated. These results show that in S. reptans, the sphincter muscle cells arise from undifferentiated hemoblasts, and that their differentiation begins with a morphological change in their nuclei. Epidermal cells and/or the ECM may have an inductive effect on muscle cell differentiation. PMID- 17867856 TI - Evolutionary relationships and reproductive isolating mechanisms in the rice frog (Fejervarya limnocharis) species complex from Sri Lanka, Thailand, Taiwan and Japan, inferred from mtDNA gene sequences, allozymes, and crossing experiments. AB - The rice frog (Fejervarya limnocharis) species complex is widely distributed, from India to Japan, and most prevalently in Southeast Asia. Conspicuous morphological variation has been reported for this species complex throughout its distribution range. In the present study, we used mtDNA gene sequence and allozyme analyses to infer evolutionary affinities within this species complex using eight populations (Sri Lanka; Bangkok and Ranong in Thailand; Taiwan; and Hiroshima, Okinawa, Ishigaki and Iriomote in Japan). We also conducted crossing experiments among four populations from Japan, Thailand, and Sri Lanka in order to find out more about the reproductive isolating mechanisms that might exist among the East, Southeast, and South Asian populations of this species complex. The crossing experiments revealed that the Sri Lanka population is reproductively isolated from the Hiroshima, Bangkok, and Ranong populations by complete hybrid inviability, and that the Bangkok population may be reproductively isolated from the Hiroshima population by partial hybrid inviability. Thus, it is not unreasonable to regard the Sri Lanka population as a species separated from F. limnocharis. The mtDNA and allozyme data showed that the Ranong population is most closely related to the Bangkok population in nuclear genome, but more similar to the Okinawa and Taiwan populations in mtDNA genome. The present, preliminary survey may raise questions about the species status of these particular populations and also about the nature of the biological species concept. PMID- 17867857 TI - An amphibious bryozoan from living mangrove leaves - Amphibiobeania new genus (Beaniidae). AB - Amphibiobeania epiphylla is a new, monotypic taxon of Beaniidae (Cheilostomata) from Darwin, Northern Territory. It is unique among the 6,000 living species of Bryozoa in that it encrusts mainly living tree leaves (chiefly the mangrove Rhizophora stylosa). The consequence of living in such a specialized habitat is that colonies are emergent (subaerial) for a significant part of the tidal cycle around 12 of every 24 hours during spring tides and for several days during neap tides. Desiccation is prevented or minimized by the high humidity of the habitat and a cohesive coating of silt covering the colony. Zooids are weakly calcified and lie alternately on their left and right sides in a lineal series, with opercula displaced to the outer corner of the distal zooidal rim. Organisms associated with A. epiphylla include a colony-damaging ceratopogonid (Diptera) larva and a tarsonemid mite that may use dead zooidal interiors, beneath the silt crust, for shelter. PMID- 17867858 TI - Relationship between algal-foraging ability and expression of sexually selected traits in male guppies. AB - In the guppy Poecilia reticulata, males exhibit orange spots on their body and tail, and the orange spot patterns are often criteria for female mate choice. The orange spot coloration of males is determined by the intake of algae, a natural source of carotenoids. Therefore, males exhibiting conspicuous orange coloration are considered to possess high algal-foraging ability. In the present study, we examined the influence of algal-foraging ability, measured by algal-searching ability and algal-foraging frequency, on the expression of orange spot patterns and on other sexually selected traits in male guppies. Males exhibiting better performance in terms of both algal-searching ability and algal-foraging frequency grew larger. The size of the orange spots on males also increased with algal foraging ability. However, neither algal-searching ability nor algal-foraging frequency influenced the coloration of the orange spots. In this experiment, a limited supply of carotenoids possibly prevented the males from completely developing their spots to the intrinsic size. The results of this study suggest that in male guppies under a carotenoid-limited situation, the allocation of carotenoids is directed toward enlargement of the size of the orange spots rather than enhancement of their coloration. Since both the body size and orange spot patterns of males contribute to their sexual attractiveness to females, high algal-foraging ability may enhance their mating success. PMID- 17867859 TI - Natriuretic peptides in cetaceans: identification, molecular characterization and changes in plasma concentration after landing. AB - Dolphins are aquatic animals free from gravity, and this may have imposed significant changes in their cardiovascular status and its hormonal regulation compared with terrestrial animals. This study molecularly characterized two major cardiovascular hormones, atrial and B-type natriuretic peptides (ANP and BNP) and measured their changes in dolphin plasma concentrations in relation to the cardiovascular status of the animal. We initially identified ANP and BNP in three species of dolphins (Lagenorhynchus obliquidens, Phocoenoides dalli and Tursiops truncatus). ANP precursors are highly conserved in most mammals, but dolphin BNP precursors were more variable. In molecular phylogenetic analyses, dolphin ANP and BNP precursors grouped with those of artiodactyls, particularly to the camel peptides. The chromatographic characterization of tissue and plasma molecular forms using specific radioimmunoassays showed that the predominant ANP and BNP in the atrium are prohormone and mature peptide, respectively, whereas mature ANP and BNP are circulating in the dolphin blood. A mass spectrometric analysis showed that atrial BNP consists of 26 amino acids, rather than the 32-amino-acid form detected in other mammals. Finally, changes in plasma ANP and BNP concentrations were examined in captive bottlenose dolphins (Tursiops truncatus) after their pool was drained. Plasma ANP and BNP concentrations did not change after landing, unlike terrestrial mammals. Plasma angiotensin II and cortisol concentrations did not change either, showing minor stress after landing. Since landed dolphins show a different cardiovascular status on land than terrestrial mammals, plasma ANP and BNP concentrations seem to reflect the cardiovascular status characteristic of dolphins. PMID- 17867860 TI - The delayed quinacrine mustard fluorescence from the C-blocks of Apodemus argenteus is due to the introduction of nicks into the DNA. AB - "Delayed QM-fluorescence" refers to the unusual kinetics of fluorescence from most of the C-heterochromatic regions of the chromosomes of the small Japanese field mouse Apodemus argenteus. When stained with quinacrine mustard (QM stained), these C-heterochromatic regions emit weak fluorescence immediately after exposure to blue light (BL); they emit bright fluorescence within a few minutes; and the intensity of the fluorescence gradually decreases after maximum fluorescence has been recorded. To elucidate the mechanism of this phenomenon, we used acridine orange staining (AO-staining) and a modified version of the in situ nick-translation method. Focusing on the large C-heterochromatic region (C-block) of the X chromosome, we noted that AO-stained C-blocks emitted greenish fluorescence, while QM-stained and BL-exposed (QM-BL-processed) C-blocks emitted reddish fluorescence upon AO-staining after removal of QM. These findings suggested that the C-block DNA of A. argenteus might undergo a structural change, such as strand breaks, during QM-BL processing. Application of the modified in situ nick-translation method revealed the generation of an appreciable number of nicks in the C-block DNA by QM-BL processing. No such nick formation was observed in the C-blocks of three other mammalian species: Apodemus peninsulae, Microtus montebelli, and Urotrichus talpoides. Our findings support the hypothesis that nick formation due to exposure to BL might play a primary role in inducing delayed QM-fluorescence in the C-blocks of A. argenteus. On the basis of the present and earlier findings, we propose a probable mechanism for delayed QM fluorescence in A. argenteus chromosomes. PMID- 17867861 TI - EcR-A expression in the brain and ovary of the honeybee (Apis mellifera L.). AB - We previously demonstrated that six genes involved in ecdysteroid signaling are expressed preferentially in Kenyon-cell subtypes in the mushroom bodies of the honeybee (Apis mellifera L.). To further examine the possible involvement of ecdysteroid signaling in honeybee brain function, we isolated a cDNA for the A isoform of the ecdysone receptor gene homolog AmEcR-A and analyzed its expression in the brain. In situ hybridization revealed that AmEcR-A is expressed selectively in the small-type Kenyon cells of the mushroom bodies in the worker and queen brain, like AmE74 and AmHR38, suggesting a possible association of these gene products. Analysis of AmEcR-A expression in queen and worker abdomens demonstrated that AmEcR-A is strongly expressed in nurse cells of the queen ovary, suggesting that ecdysteroid and ecdysteroid signaling have roles in oogenesis. Our present results further support the possible involvement of ecdysteroid signaling in brain function, as well as in regulating queen reproductive physiology in the adult honeybee. PMID- 17867862 TI - Effects of unilateral compound-eye removal on the photoperiodic responses of nymphal development in the cricket Modicogryllus siamensis. AB - The cricket, Modicogryllus siamensis, shows clear photoperiodic responses at 25 degrees C in nymphal development. Under long-day conditions (LD16:8), nymphs became adults about 50 days after hatching, while under short-day conditions (LD8:16) the duration of nymphal stage extended to more than 130 days. Under constant dark conditions, two developmental patterns were observed: about 60% of crickets became adults slightly slower than under the long-day conditions, and the rest at later than 100 days after hatching, like those under the short-day conditions. When the compound eye was unilaterally removed on the 2nd day of hatching, an increase of molting and an extension of the nymphal period were observed under the long-day conditions, while under the short-day conditions, some crickets developed faster and others slower than intact crickets. These results suggest that this cricket receives photoperiodic information through the compound eye, that a pair of the compound eyes is required for a complete photoperiodic response, and that interaction between bilateral circadian clocks may be also involved in the response. PMID- 17867863 TI - Sexual difference in color sense in a lycaenid butterfly, Narathura japonica. AB - The spectral sensitivity of a lycaenid butterfly, Narathura japonica, was investigated by electroretinography using an integrating sphere that could illuminate the compound eye from almost all directions. Samples were collected from three locations. Butterflies from different locations showed a similar pattern; the first, second, and third peaks (or a shoulder) were located at about 380, 460, and 560 nm, respectively. Males clearly showed the highest sensitivity at the first peak point. In contrast, females showed a higher relative sensitivity than males at the second and third peak points in all samples, and showed broad spectral sensitivity. This male-specific UV-sensitivity is discussed in terms of ecological factors. PMID- 17867864 TI - Annual reproductive cycle of a bitterling, Tanakia tanago, reared in an outdoor tank. AB - From June 2000 to September 2001, we investigated the presence of eggs spawned in Margaritifera laevis and the seasonal changes in the gonads of Tanakia tanago. Eggs were observed from mid-March to mid-September. In females with a shrunken ovipositor, as the GSI gradually increased, most ovaries were in the prespawning phase (Oct-Mar). As the GSI increased further, most ovaries were in the early spawning phase (Mar-Jun). As the GSI gradually deceased, ovaries in the late spawning phase appeared (Jun-Sep). When the GSI was very low, most ovaries were in the postspawning phase (Sep-Oct). In males, when the GSI was low, most testes were in the early prespawning phase from Oct-Dec. As the GSI gradually increased, most testes were in the late prespawning phase (Dec-Jan). As the GSI increased further, testes were in the early spawning phase (Jan-Jun). As the GSI gradually decreased, amost testes were in the late spawning phase (Jun-Sep). When the GSI was very low, most testes were in the postspawning phase (Sep-Oct). These results indicate that T. tanago has a distinct annual reproductive cycle and is a spring autumn spawner. Based on the relationship between reproductive activity and environmental factors, the spawning season of T. tanago appears to be initiated by increasing temperature and / or longer days in spring and to be terminated by shorter days in autumn. PMID- 17867865 TI - Pseudobiotus spinifer, a new tardigrade species (Eutardigrada: Hypsibiidae) from Nakdong River, South Korea, with a redescription of P. vladimiri Biserov, Dudichev & Biserova. AB - A new freshwater tardigrade species, Pseudobiotus spinifer sp. nov., is described from the sand bottom of Nakdong River, South Korea. The new species is most similar to Pseudobiotus vladimiri from Biwa Lake, Japan, but differs from it by having small accessory points ending in the center of the primary branches of all claws, relatively longer claws and macroplacoids, and well developed cuticular spines/spicules over most of the dorsal and lateral surfaces of the body. Pseudobiotus vladimiri is redescribed on the basis of the holotype. A revised key to the species of the genus Pseudobiotus is also given. PMID- 17867866 TI - Freshwater bryozoa of Tonle Sap, Cambodia. AB - We identified a collection of freshwater bryozoans from Tonle Sap (meaning Tonle Lake), Cambodia, a body of water fed by the Mekong River and characterized by extreme fluctuations in water level between the wet and dry seasons. The collection also included specimens from the moat of Angkor Wat, located at the north end of the lake. We found four phylactolaemate species (Plumatella bombayensis, Plumatella casmiana, Plumatella vorstmani, Hyalinella lendenfeldi) and one ctenostome species (Hislopia cambodgiensis) from the lake, and only a single, additional phylactolaemate species (Plumatella javanica) from the moat. We provide brief descriptions of these species, photographs of colonies for some, and photomicrographs by light and scanning electron microscopy (SEM) of statoblasts. None of the species encountered in this study is endemic to Cambodia, and the wide distributions of the species are possibly related to the dispersability of floatoblasts by birds. We briefly discuss some of the taxonomic problems surrounding Hislopia cambodgiensis. PMID- 17867867 TI - Lethal and sublethal effects of ammonia to juvenile Lampsilis mussels (Unionidae) in sediment and water-only exposures. AB - We compared the sensitivity of two juvenile unionid mussels (Lampsilis cardium and Lampsilis higginsii) to ammonia in 96-h water-only and sediment tests by use of mortality and growth measurements. Twenty mussels were placed in chambers buried 2.5 cm into reference sediments to approximate pore-water exposure (sediment tests) or elevated above the bottom of the experimental units (water only tests). In the sediment tests, a pH gradient existed between the overlying water (mean 8.0), sediment- water interface (mean 7.7), and 2.5 cm depth (mean 7.4). We assumed that mussels were exposed to ammonia in pore water and report effect concentrations in pore water, but if they were exposed to the higher pH water, more of the ammonia would be in the toxic un-ionized (NH(3)) form. The only differences in toxicity and growth between mussel species occurred in some of the water-only tests. In sediment tests, median lethal concentrations (LC50s) ranged from 124 to 125 microg NH(3)-N/L. In water-only tests, LC50s ranged from 157 to 372 microg NH(3)-N/L. In sediment tests, median effective concentrations (EC50s based on growth) ranged from 30 to 32 microg NH(3)-N/L. Juvenile mussels in the water-only tests grew poorly and did not exhibit a dose-response relation. These data demonstrate that growth is a sensitive and valuable endpoint for studies on ammonia toxicity with juvenile freshwater mussels and that growth should be measured via sediment tests. PMID- 17867868 TI - Subchronic organismal toxicity, cytotoxicity, genotoxicity, and feeding response of Pacific oyster (Crassostrea gigas) to lindane (gamma-HCH) exposure under experimental conditions. AB - This study evaluated organismal toxicity, cytotoxicity, and genotoxicity and the filtration rate in response to different concentrations of subchronic lindane (gamma-hexachlorocyclohexane [gamma-HCH]), exposure (12 d) in adult Pacific oysters Crassostrea gigas. Oysters were exposed in vivo in laboratory aquaria to 10 different concentrations (0.0-10.0 mg/L) of gamma-HCH. The median lethal concentration (LC50) after 12 d was calculated as 2.22 mg/L. Cytotoxic effects were observed in hemocytes, where the mean cell viability was significantly decreased at 1.0 mg/L of gamma-HCH after 12 d. Genotoxicity of gamma-HCH measured by single cell gel electrophoresis assay, in hemocytes was evident at 0.7 mg/L of gamma-HCH after 12 d. After 4 h of exposure to gamma-HCH, filtration rates were reduced compared with controls to 65.8 and 38.2% at concentrations of 0.3 and 0.7 mg/L, respectively, and after 11 d of exposure, filtration rates were reduced to 60.4 and 30.9% at concentrations of 0.1 mg/L and higher. These results show the subchronic effects of gamma-HCH at different concentrations and effect sensitivities are categorized as filtration rate < genotoxicity < cytotoxicity < mortality. The relevance of integral toxicity evaluation, considering different endpoints from molecular, cellular, and individual levels is discussed. PMID- 17867869 TI - Acute silver toxicity in the euryhaline copepod Acartia tonsa: influence of salinity and food. AB - The euryhaline copepod Acartia tonsa was exposed to silver (AgNO(3)) in either the absence or the presence of food (diatom Thalassiosira weissflogii; 2 x 10(4) cells/ml). Standard static-renewal toxicity tests that included a fixed photoperiod of 16: 8 h light:dark and temperature (20 degrees C) were run in three different salinities (5, 15, and 30 ppt) together with measurements of pH, ions (Na(+), Cl(-), K(+), SO(4)(2-), Mg(2+), and Ca(2+)), alkalinity, dissolved organic carbon, and total and dissolved (0.45 microm) silver concentrations in the experimental media. In the absence of food, the 48-h EC50 (concentration causing effect to 50% of the individuals tested) values based on total and dissolved silver concentrations were 11.6, 87.2, and 163.2 microg Ag/L and 7.1, 79.2, and 154.6 microg Ag/L at salinities 5, 15, and 30 ppt, respectively. In the presence of food, they were 62.1, 98.5, and 238.4 microg Ag/L and 48.4, 52.3, and 190.9 microg Ag/L, respectively. In all experimental conditions, most of the toxic silver fraction was in the dissolved phase, regardless of salinity or the presence of food in the water. In either the absence or the presence of food, acute silver toxicity was salinity dependent, decreasing as salinity increased. Data indicate that changes in water chemistry can account for the differences in acute silver toxicity in the absence of food, but not in the presence of food, suggesting that A. tonsa requires extra energy to cope with the stressful conditions imposed by acute silver exposure and ionoregulatory requirements in low salinities. These findings indicate the need for incorporation of both salinity and food (organic carbon) in a future biotic ligand model (BLM) version for estuarine and marine conditions, which could be validated and calibrated using the euryhaline copepod A. tonsa. PMID- 17867870 TI - Acute and chronic toxicity of glyphosate compounds to glochidia and juveniles of Lampsilis siliquoidea (Unionidae). AB - Native freshwater mussels (family Unionidae) are among the most imperiled faunal groups in the world. Factors contributing to the decline of mussel populations likely include pesticides and other aquatic contaminants; however, there is a paucity of data regarding the toxicity of even the most globally distributed pesticides, including glyphosate, to mussels. Therefore, the toxicity of several forms of glyphosate, its formulations, and a surfactant (MON 0818) used in several glyphosate formulations was determined for early life stages of Lampsilis siliquoidea, a native freshwater mussel. Acute and chronic toxicity tests were performed with a newly established American Society of Testing and Materials (ASTM) standard guide for conducting toxicity tests with freshwater mussels. Roundup, its active ingredient, the technical-grade isopropylamine (IPA) salt of glyphosate, IPA alone, and MON 0818 (the surfactant in Roundup formulations) were each acutely toxic to L. siliquoidea glochidia. MON 0818 was most toxic of the compounds tested and the 48-h median effective concentration (0.5 mg/L) for L. siliquoidea glochidia is the lowest reported for any aquatic organism tested to date. Juvenile L. siliquoidea were also acutely sensitive to MON 0818, Roundup, glyphosate IPA salt, and IPA alone. Technical-grade glyphosate and Aqua Star were not acutely toxic to glochidia or juveniles. Ranking of relative chronic toxicity of the glyphosate-related compounds to juvenile mussels was similar to the ranking of relative acute toxicity to juveniles. Growth data from chronic tests was largely inconclusive. In summary, these results indicate that L. siliquoidea, a representative of the nearly 300 freshwater mussel taxa in North America, is among the most sensitive aquatic organisms tested to date with glyphosate-based chemicals and the surfactant MON 0818. PMID- 17867871 TI - Intra- and interlaboratory variability in acute toxicity tests with glochidia and juveniles of freshwater mussels (Unionidae). AB - The present study evaluated the performance and variability in acute toxicity tests with glochidia and newly transformed juvenile mussels using the standard methods outlined in American Society for Testing and Materials (ASTM). Multiple 48-h toxicity tests with glochidia and 96-h tests with juvenile mussels were conducted within a single laboratory and among five laboratories. All tests met the test acceptability requirements (e.g., >or=90% control survival). Intralaboratory tests were conducted over two consecutive mussel-spawning seasons with mucket (Actinonaias ligamentina) or fatmucket (Lampsilis siliquoidea) using copper, ammonia, or chlorine as a toxicant. For the glochidia of both species, the variability of intralaboratory median effective concentrations (EC50s) for the three toxicants, expressed as the coefficient of variation (CV), ranged from 14 to 27% in 24-h exposures and from 13 to 36% in 48-h exposures. The intralaboratory CV of copper EC50s for juvenile fatmucket was 24% in 48-h exposures and 13% in 96-h exposures. Interlaboratory tests were conducted with fatmucket glochidia and juveniles by five laboratories using copper as a toxicant. The interlaboratory CV of copper EC50s for glochidia was 13% in 24-h exposures and 24% in 48-h exposures, and the interlaboratory CV for juveniles was 22% in 48-h exposures and 42% in 96-h exposures. The high completion success and the overall low variability in test results indicate that the test methods have acceptable precision and can be performed routinely. PMID- 17867872 TI - Acute and chronic toxicity of technical-grade pesticides to glochidia and juveniles of freshwater mussels (Unionidae). AB - Chemical contaminants are among many potential factors involved in the decline of freshwater mussel populations in North America, and the effects of pesticides on early life stages of unionid mussels are largely unknown. The objective of this study was to determine the toxicity of technical-grade current-use pesticides to glochidia and juvenile life stages of freshwater mussels. We performed acute toxicity tests with glochidia (five species) and juveniles (two species) exposed to a suite of current-use pesticides including herbicides (atrazine and pendimethalin), insecticides (fipronil and permethrin), and a reference toxicant (NaCl). Because of limited availability of test organisms, not all species were tested with all pesticides. Toxicity tests with fungicides (chlorothalonil, propiconazole, and pyraclostrobin) were performed with one species (Lampsilis siliquoidea). Lampsilis siliquoidea glochidia and juveniles were highly sensitive to the fungicides tested but the technical-grade herbicides and insecticides, at concentrations approaching water solubility, were not acutely toxic to this or the other unionid species. In a 21-d chronic test with four-month-old juvenile L. siliquoidea, the 21-d median effective concentration (EC50) with atrazine was 4.3 mg/L and in atrazine treatments >or=3.8 mg/L mussel growth was significantly less than controls. The relatively high sensitivity of L. siliquoidea to chlorothalonil, propiconazole, and pyraclostrobin is similar to that reported for other aquatic organisms commonly used for toxicity testing. The relative risk associated with acute exposure of early life stages of mussels to technical-grade atrazine, pendimethalin, fipronil, and permethrin is likely low; however, survival and growth results with juvenile L. siliquoidea indicate that chronic exposure to high concentrations (>/=3.8 mg/L) of atrazine may have the potential to impact mussel populations and warrants further investigation. PMID- 17867873 TI - Acute toxicity of copper, ammonia, and chlorine to glochidia and juveniles of freshwater mussels (Unionidae). AB - The objective of the present study was to determine acute toxicity of copper, ammonia, or chlorine to larval (glochidia) and juvenile mussels using the recently published American Society for Testing and Materials (ASTM) Standard guide for conducting laboratory toxicity tests with freshwater mussels. Toxicity tests were conducted with glochidia (24- to 48-h exposures) and juveniles (96-h exposures) of up to 11 mussel species in reconstituted ASTM hard water using copper, ammonia, or chlorine as a toxicant. Copper and ammonia tests also were conducted with five commonly tested species, including cladocerans (Daphnia magna and Ceriodaphnia dubia; 48-h exposures), amphipod (Hyalella azteca; 48-h exposures), rainbow trout (Oncorhynchus mykiss; 96-h exposures), and fathead minnow (Pimephales promelas; 96-h exposures). Median effective concentrations (EC50s) for commonly tested species were >58 microg Cu/L (except 15 microg Cu/L for C. dubia) and >13 mg total ammonia N/L, whereas the EC50s for mussels in most cases were <45 microg Cu/L or <12 mg N/L and were often at or below the final acute values (FAVs) used to derive the U.S. Environmental Protection Agency 1996 acute water quality criterion (WQC) for copper and 1999 acute WQC for ammonia. However, the chlorine EC50s for mussels generally were >40 microg/L and above the FAV in the WQC for chlorine. The results indicate that the early life stages of mussels generally were more sensitive to copper and ammonia than other organisms and that, including mussel toxicity data in a revision to the WQC, would lower the WQC for copper or ammonia. Furthermore, including additional mussel data in 2007 WQC for copper based on biotic ligand model would further lower the WQC. PMID- 17867874 TI - Chronic toxicity of copper and ammonia to juvenile freshwater mussels (Unionidae). AB - The objectives of the present study were to develop methods for conducting chronic toxicity tests with juvenile mussels under flow-through conditions and to determine the chronic toxicity of copper and ammonia to juvenile mussels using these methods. In two feeding tests, two-month-old fatmucket (Lampsilis siliquoidea) and rainbow mussel (Villosa iris) were fed various live algae or nonviable algal mixture for 28 d. The algal mixture was the best food resulting in high survival (>or=90%) and growth. Multiple copper and ammonia toxicity tests were conducted for 28 d starting with two-month-old mussels. Six toxicity tests using the algal mixture were successfully completed with a control survival of 88 to 100%. Among copper tests with rainbow mussel, fatmucket, and oyster mussel (Epioblasma capsaeformis), chronic value ([ChV], geometric mean of the no observed-effect concentration and the lowest-observed-effect concentration) ranged from 8.5 to 9.8 microg Cu/L for survival and from 4.6 to 8.5 microg Cu/L for growth. Among ammonia tests with rainbow mussel, fatmucket, and wavy-rayed lampmussel (L. fasciola), the ChV ranged from 0.37 to 1.2 mg total ammonia N/L for survival and from 0.37 to 0.67 mg N/L for growth. These ChVs were below the U.S. Environmental Protection Agency 1996 chronic water quality criterion (WQC) for copper (15 microg/L; hardness 170 mg/L) and 1999 WQC for total ammonia (1.26 mg N/L; pH 8.2 and 20 degrees C). Results indicate that toxicity tests with two month-old mussels can be conducted for 28 d with >80% control survival; growth was frequently a more sensitive endpoint compared to survival; and the 1996 chronic WQC for copper and the 1999 chronic WQC for total ammonia might not be adequately protective of the mussel species tested. However, a recently revised 2007 chronic WQC for copper based on the biotic ligand model may be more protective in the water tested. PMID- 17867875 TI - Acute and chronic toxicity of pesticide formulations (atrazine, chlorpyrifos, and permethrin) to glochidia and juveniles of Lampsilis siliquoidea. AB - Freshwater mussels are among the most imperiled faunal groups in North America; approximately 67% of the nearly 300 native freshwater mussel species (family Unionidae) are listed as endangered, threatened, or of special concern. Despite evidence that glochidia and juvenile life stages are highly sensitive to some chemical contaminants, the effects of pesticides on early life stages of unionid mussels are largely unknown. In the United States, pesticide registration is based on toxicity data of the active ingredient, not formulations as they are sold and applied. Some pesticide formulations, however, are more toxic than their active ingredient (technical-grade pesticide) alone because of the presence of surfactants, adjuvants, or other ingredients in the formulation. The objective of the present study was to compare the toxicity of active ingredients of several current-use pesticides (atrazine, chlorpyrifos, and permethrin) to the toxicity of pesticide formulations to glochidia and juvenile life stages of a freshwater mussel (Lampsilis siliquoidea). The atrazine formulation (Aatrex) was more toxic than technical-grade atrazine in chronic tests with juvenile L. siliquoidea. For other pesticides, acute and chronic toxicity of technical-grade pesticides were similar to the toxicity of pesticide formulations. Median effective concentrations for chlorpyrifos were 0.43 mg/L for glochidia at 48 h, 0.25 mg/L for juveniles at 96 h, and 0.06 mg/L for juveniles at 21 d. Atrazine and permethrin as well as their formulations did not cause significant acute toxicity in glochidia or juveniles at exposure concentrations approaching water-solubility limits. Additional research is needed on other pesticides with different modes of action, on the role of different routes of exposure, and with other species of unionid mussels to evaluate similarities of toxic response. PMID- 17867876 TI - An evaluation of freshwater mussel toxicity data in the derivation of water quality guidance and standards for copper. AB - The state of Oklahoma has designated several areas as freshwater mussel sanctuaries in an attempt to provide freshwater mussel species a degree of protection and to facilitate their reproduction. We evaluated the protection afforded freshwater mussels by the U.S. Environmental Protection Agency (U.S. EPA) hardness-based 1996 ambient copper water quality criteria, the 2007 U.S. EPA water quality criteria based on the biotic ligand model and the 2005 state of Oklahoma copper water quality standards. Both the criterion maximum concentration and criterion continuous concentration were evaluated. Published acute and chronic copper toxicity data that met American Society for Testing and Materials guidance for test acceptability were obtained for exposures conducted with glochidia or juvenile freshwater mussels. We tabulated toxicity data for glochidia and juveniles to calculate 20 species mean acute values for freshwater mussels. Generally, freshwater mussel species mean acute values were similar to those of the more sensitive species included in the U.S. EPA water quality derivation database. When added to the database of genus mean acute values used in deriving 1996 copper water quality criteria, 14 freshwater mussel genus mean acute values included 10 of the lowest 15 genus mean acute values, with three mussel species having the lowest values. Chronic exposure and sublethal effects freshwater mussel data available for four species and acute to chronic ratios were used to evaluate the criterion continuous concentration. On the basis of the freshwater mussel toxicity data used in this assessment, the hardness-based 1996 U.S. EPA water quality criteria, the 2005 Oklahoma water quality standards, and the 2007 U.S. EPA water quality criteria based on the biotic ligand model might need to be revised to afford protection to freshwater mussels. PMID- 17867877 TI - Risk assessment of water quality in three North Carolina, USA, streams supporting federally endangered freshwater mussels (Unionidae). AB - Water quality data were collected from three drainages supporting the endangered Carolina heelsplitter (Lasmigona decorata) and dwarf wedgemussel (Alasmidonta heterodon) to determine the potential for impaired water quality to limit the recovery of these freshwater mussels in North Carolina, USA. Total recoverable copper, total residual chlorine, and total ammonia nitrogen were measured every two months for approximately a year at sites bracketing wastewater sources and mussel habitat. These data and state monitoring datasets were compared with ecological screening values, including estimates of chemical concentrations likely to be protective of mussels, and federal ambient water quality criteria to assess site risks following a hazard quotient approach. In one drainage, the site specific ammonia ecological screening value for acute exposures was exceeded in 6% of the samples, and 15% of samples exceeded the chronic ecological screening value; however, ammonia concentrations were generally below levels of concern in other drainages. In all drainages, copper concentrations were higher than ecological screening values most frequently (exceeding the ecological screening values for acute exposures in 65-94% of the samples). Chlorine concentrations exceeding the acute water quality criterion were observed in 14 and 35% of samples in two of three drainages. The ecological screening values were exceeded most frequently in Goose Creek and the Upper Tar River drainages; concentrations rarely exceeded ecological screening values in the Swift Creek drainage except for copper. The site-specific risk assessment approach provides valuable information (including site-specific risk estimates and ecological screening values for protection) that can be applied through regulatory and nonregulatory means to improve water quality for mussels where risks are indicated and pollutant threats persist. PMID- 17867878 TI - Extraction and bioanalysis of the ecotoxicologically relevant fraction of contaminants in sediments. AB - Assessments of the risk connected to the contamination of soils and sediments should rely on a multidisciplinary approach based on both chemical and biological techniques (i.e., the sum of exposure and effects assessment). The dioxin responsive, chemical-activated luciferase expression (DR-CALUX) bioassay is widely applied for evaluation of the toxicity of sediments after an exhaustive extraction of the contaminants, and results are used for risk assessment purposes. Approaches based on total extraction of contaminants do not take into account the importance of bioavailability and aging processes, thus leading to possible overestimations of risk. In the present work, an approach based on nonexhaustive extraction techniques in combination with an in vitro reporter gene assay was tested on sediment samples contaminated with dioxins, polycyclic aromatic hydrocarbons, polychlorinated biphenyls (PCBs), and other xenobiotics. Tenax and hydroxypropyl-beta-cyclodextrin (HPCD) extractions over time were carried out to determine the bioavailable fractions, whereas the residual fractions were determined by means of a microwave-assisted exhaustive extraction. For both fractions, contaminant concentrations were quantified by gas chromatography-mass spectrophotometry, and the toxic potency was determined by the DR-CALUX assay. Assessments of bioavailable fractions of PCBs by Tenax and HPCD gave comparable results and showed that after several years of aging, a considerable fraction (38-70% of the total content for different PCBs) is still available and ecotoxicologically relevant. Coupling of nonexhaustive extraction and bioanalyses leads to a more realistic and, generally, much lower estimated risk for the toxicity of the extracts as compared to commonly adopted exhaustive techniques. PMID- 17867879 TI - Spatial and temporal evaluation of metal concentrations in soils and sediments from New Orleans, Louisiana, USA, following hurricanes Katrina and Rita. AB - During January 2006, soil and sediment samples from 75 sites in the New Orleans (LA, USA) area were collected and tested for 26 inorganic elements. The study design was intended to provide a spatial pattern of metal concentrations within the city following hurricanes Katrina and Rita. The sampling design included four transects that traversed the city in a north-south direction and three transects that traversed the city in an east-west direction. Contaminant concentrations were determined at multiple sites within each transect and compared to U.S. Environmental Protection Agency soil screening criteria pertaining to human health. Concentrations of Pb and As exceeded the criteria indiscriminately throughout the city. Of the 75 sites, 14 (19%) exceeded the soil screening criteria for Pb, and 73 (97%) exceeded the criteria for As. Forty-three of the 75 sites coincided with a previous sampling event in October 2005. Metal concentrations were evaluated for temporal comparisons using a pair sampled t test. Arsenic concentrations differed significantly over time, but Pb concentrations did not. PMID- 17867880 TI - Use of the Australian crimson-spotted rainbowfish (Melanotaenia fluviatilis) as a model test species for investigating the effects of endocrine disruptors. AB - Few studies have investigated the potential reproductive effects of toxicants on Australian freshwater fish species. The present study uses the Australian rainbowfish (Melanotaenia fluviatilis) as a model for testing the potential effects of 17beta-estradiol. Groups of reproductively active rainbowfish were exposed to waterborne 17beta-estradiol (control, carrier control, and 30, 100, 300, and 1,000 ng/L) for 3- and 14-d periods. Biomarkers of both low ecological relevance (plasma estradiol and testosterone, phosphoprotein, gamma glutamyltranspeptidase [GTP]) and high ecological relevance (egg counts, hatchability, larval lengths, histopathology) were measured and the relationships between these examined. Relative to the controls, exposed female rainbowfish had a decline in plasma estradiol. An increase in phosphoprotein (vitellogenin) also was observed after exposure to 1,000 ng/L after 3 d, and histological examination of the gonads showed an increase in oocyte atresia at 1,000 ng/L on days 3 and 14. Changes in egg production were observed at 300 and 1,000 ng/L. No changes were detected to egg hatchability and larval lengths of offspring. Although there were no changes in male rainbowfish plasma testosterone or the histological organization of testes, levels of phosphoprotein increased and GTP activities were increased after 3 d of exposure at all test concentrations, but these declined at day 14. The present study demonstrated that, though measurements at the biochemical level were responsive to 17beta-estradiol exposure, fewer changes were observed in markers of higher ecological relevance at the exposures concentrations and durations tested. PMID- 17867881 TI - Can the unit world model concept be applied to hazard assessment of both organic chemicals and metal ions? AB - A unit world model that has the potential to be used for the hazard assessment of both metal ions and organic chemicals is described and discussed, with an emphasis on the problems that arise when treating metal ions. It is based on the steady-state equilibrium criterion model that is designed to simulate the fate of organic chemicals in a 100,000-km(2) region and comprises four well-mixed compartments: Air, water, soil, and sediment. To be applicable to metal ions, modifications are required. The single soil and sediment layers should be replaced by two layers to accommodate aerobic and anaerobic conditions. The more complex and variable partitioning of metals resulting from dependence on pH, redox conditions, ionic oxidation state, and presence of sulfide also must be addressed, but preferably in a separate geochemical model, because these factors can result in nonlinearity. For metals, a dynamic as well as a steady-state model is desirable. It is shown that the resulting model can be applied to both organics and metals. Rather than seeking to apply the hazard criterion of persistence to metal ions, the model can be used to deduce a critical loading that results in a defined toxic end point, thus integrating the hazard criteria of persistence, toxicity, and possibly, bioaccumulation. This approach is applied illustratively to naphthalene as a typical organic substance and to four environmentally relevant metal ions. Results are discussed and recommendations made for further development. Specifically, the absence of metal degradation can result in large, steady-state quantities in soils and sediments corresponding to residence times of many centuries. Consequently, the dynamic calculations are more relevant for fate assessments of metals over a period of years, and more focus on the aquatic environment is justified. PMID- 17867882 TI - Validation study of the acute biotic ligand model for silver. AB - An important final step in development of an acute biotic ligand model for silver is to validate predictive capabilities of the biotic ligand model developed for fish and invertebrates. To accomplish this, eight natural waters, collected from across North America, were characterized with respect to ionic composition, pH, dissolved organic carbon, and sulfide. Tests were conducted with the cladoceran Ceriodaphnia dubia (48-h static) and the fish Pimephales promelas (96-h static renewal) to determine the concentrations causing lethality to 50% of the organisms (LC50s) for silver in each of these waters. Overall, the biotic ligand model adequately predicted silver toxicity to C. dubia; however, in some cases, predicted LC50 values exceeded measured values. The accuracy of the biotic ligand model predictions was less convincing for silver toxicity to P. promelas with pronounced problems in low-ionic strength waters. Another issue was the use of acclimated organisms in toxicity studies because the biotic ligand model has been developed with the use of a mix of studies with acclimated and nonacclimated test organisms of varying ages and sizes. To evaluate whether effects of acclimation to test waters influence biotic ligand model predictions, a subset of the natural waters were also tested with P. promelas that had been acclimated to the natural water for 7 d before testing. These experiments revealed no differences in toxicity between acclimated and nonacclimated P. promelas. To determine the influence of organism size, which has been previously correlated to Na(+) turnover and acute silver toxicity across multiple species, Na(+) and Cl(-) influx rates were measured in P. promelas of different sizes. Our results show that Na(+) and Cl(-) influx rates were inversely related to fish mass and positively correlated with silver sensitivity. PMID- 17867883 TI - Dynamics of benazolin under the influence of degrading maize straw in undisturbed soil columns. AB - The effect of organic carbon amendment on the fate of benazolin was investigated in undisturbed soil columns. The soil columns were obtained from three different soil types located in three different regions with different crop production regimes. All soils were operated in a normal crop production regime, and one of the soils was additionally operated in low and high crop production regimes. Two experimental setups were conducted, one using [(14)C]maize straw and nonlabeled benazolin and one using nonlabeled maize straw and [(14)C]benazolin. The column experiments with [(14)C]maize straw showed that the residual crop residues remained mainly in the top layer. Benazolin and its metabolites showed a higher retention in columns that were amended with maize straw compared to column without amendment. The production regimes of the soils did not influence the behavior of benazolin. The effect of maize straw incorporation on the translocation and degradation of benazolin could well be caused by a change in the soil microbial activity, leading to an enhanced degradation of benazolin and producing metabolites exhibiting a sorption behavior different from the parent. PMID- 17867884 TI - Advances and opportunities in assessing contaminant sensitivity of freshwater mussel (Unionidae) early life stages. PMID- 17867885 TI - An individual-based approach to model spatial population dynamics of invertebrates in aquatic ecosystems after pesticide contamination. AB - In the present study we present a population model (Metapopulation model for Assessing Spatial and Temporal Effects of Pesticides [MASTEP]) describing the effects on and recovery of the waterlouse Asellus aquaticus after exposure to a fast-acting, nonpersistent insecticide as a result of spray drift in pond, ditch, and stream scenarios. The model used the spatial and temporal distribution of the exposure in different treatment conditions as an input parameter. A dose-response relation derived from a hypothetical mesocosm study was used to link the exposure with the effects. The modeled landscape was represented as a lattice of 1- by 1-m cells. The model included processes of mortality of A. aquaticus, life history, random walk between cells, density dependence of population regulation, and, in the case of the stream scenario, medium-distance drift of A. aquaticus due to flow. All parameter estimates were based on expert judgment and the results of a thorough review of published information on the ecology of A. aquaticus. In the treated part of the water body, the ditch scenario proved to be the worst-case situation, due to the absence of drift of A. aquaticus. Effects in the pond scenario were smaller because the pond was exposed from one side, allowing migration from the other, less contaminated side. The results of the stream scenario showed the importance of including drift for the population recovery in the 100-m stretch of the stream that was treated. It should be noted, however, that the inclusion of drift had a negligible impact on numbers in the stream as a whole (600 m). PMID- 17867886 TI - A control chart approach to monitoring and communicating trends in tissue selenium concentrations. AB - A primary aim of monitoring programs is to determine changes relative to background conditions, which typically represent a distribution of values, not a single value, and which may be elevated naturally. Graphical inspection of the statistical distribution of background and subsequent data provides the best means to determine changes over time and the relative significance of those changes based on both their magnitude and trajectory. The control chart approach commonly used in laboratory and product testing is a useful tool that allows for such determinations in a manner that is transparent to both scientists and nonscientists. This approach can be used both with true baseline (i.e., pre development) data and with operational baseline (i.e., post-development) data and is particularly relevant for monitoring selenium (Se) tissue concentrations. PMID- 17867887 TI - Are songbirds at risk from lead at small arms ranges? An application of the spatially explicit exposure model. AB - Use of small arms during training is an important activity associated with the development and proficiency of soldiers. These weapons traditionally have used copper-jacketed lead projectiles; the copper facilitates the oxidation of the metallic lead resulting in more mobile oxides and carbonates. Consequently, many ranges at installations have high soil concentrations of lead. Many of these ranges are no longer used and have become habitat for wildlife. To address the potential for adverse effects from lead exposure in songbirds, we compared the outputs of traditional deterministic exposure models with a spatial model and compared the results of both with blood-lead levels from songbird species at two small arms range complexes. An integrative data collection procedure was used and incorporated into the spatially explicit exposure model (SEEM) for two small arms range sites. Site-specific data were used to refine model input parameters. These data included lead soil concentrations, analysis of lead concentrations in nestling food items, acid-insoluble ash content of feces (to estimate soil ingestion), location and mapping of singing males, and nest site location and characteristics. Territorial males also were spot-mapped to determine likelihood of breeding activity. Modeled estimates of risk were compared with blood and feather lead levels of adults and nestlings. Overall, edge species had higher blood-lead concentrations; however, most had concentrations below subclinical effect levels. Conventional deterministic methods produced risk estimates exceeding 10-fold the highest SEEM estimates. The spatially explicit exposure model provided good agreement with field observations and therefore produced more accurate risk estimates. The present study provides support for the application of spatial methods over conventional deterministic methods. PMID- 17867888 TI - Effects of dilution on the exposure in sediment toxicity tests- buffering of freely dissolved concentrations and changes in mixture composition. AB - Some sediment toxicity tests, such as the Microtox test, are conducted by diluting either contaminated sediment or an aqueous phase with clean water. The present study aims to clarify how the dilution procedure affects the exposure of organisms. It is shown that freely dissolved concentrations of hydrophobic compounds are buffered by desorption from the sediment matrix when sediment is diluted with water. The buffering depends on the properties of the sediment matrix and contaminant. Consequently, the composition of a contaminant mixture changes with dilution, and the exposure in a sediment dilution toxicity test is poorly defined. This questions the application and subsequent assessments of such tests. Additionally, the often-observed higher toxicity in sediment dilution tests relative to elutriate dilution tests is not sufficient to claim direct contact exposure, because the enhanced sensitivity in sediment dilution tests also can be explained by buffering from the sediment matrix. In applying these tests, one should be aware of the fundamental differences between the sediment dilution strategy and the dilution of an aqueous phase and of the consequences it has for the outcome of the test. PMID- 17867889 TI - Effects of subchronic exposure to 2,6-dinitrotoluene in the northern bobwhite (Colinus virginianus). AB - Explosives and their breakdown products are commonly found in soils at U.S. military installations. Many areas where these compounds are found represent useful habitat for ground-foraging birds. Because these birds likely are exposed to such compounds, we evaluated the oral toxicity of 2,6-dinitrotoluene (DNT) in a representative ground-foraging species of management concern. Adult male and female northern bobwhite (Colinus virginianus) were exposed to either 0, 5, 10, 40, or 60 mg/kg/d via gavage for 60 d (subchronic) following determination of the median acute lethal dose (320 mg/kg). Circulating levels of red blood cells and hemoglobin were significantly decreased in a dose-dependent manner; however, levels remained within normal ranges. Plasma concentrations of total protein, albumin, globulin, aspartate aminotransferase, and potassium, sodium, and chlorine ions were significantly decreased, and circulating levels of uric acid were significantly increased. Decreased body weight, enlarged gallbladders, edematous gastrointestinal tracts, pale kidneys, pale and fibrous livers, and loose stools were consistent observations. The effects found in the clinical chemistries taken together with histopathological abnormalities observed in sections of hepatic and renal tissue suggest that the liver and kidneys are major targets for 2,6-DNT. Oral exposures to 2,6-DNT appear to affect northern bobwhite in a manner similar to that of the other main DNT isomer, 2,4-DNT, but in more subtle ways, adversely affecting the gastrointestinal system and leading to diarrhea and, ultimately, emaciation. The lowest-observed-adverse-effect level is 40 mg/ kg/d based on hematological measures, and the no-observed-adverse-effect level is 10 mg/kg/d based on the absence of results indicative of adverse effects. PMID- 17867890 TI - Ecotoxicity and genotoxicity assessment of cytostatic pharmaceuticals. AB - The fate and effects of cytostatic (anticancer or antineoplastic) pharmaceuticals in the environment are largely unknown, but they can contaminate wastewater treatment effluents and consequently aquatic ecosystems. In this paper, we have focused on five cytostatic compounds used in high amounts (cyclophosphamide, cisplatin, 5-fluorouracil, doxorubicin, and etoposide), and we have investigated their ecotoxicity in bacterial Pseudomonas putida growth-inhibition test, algal Pseudokirchneriella subcapitata growth-inhibition test, and Dapnia magna acute immobilization test. Genotoxicity also was assessed with Escherichia coli SOS chromotest (with and without metabolic activation) and the GreenScreen Assay using yeast S. cerevisiae. All tested compounds showed significant effects in most of the assays with lowest-observed-effect concentrations and concentrations causing 50% effects (EC50s) values ranging within microg/L to mg/L. The most toxic compound was 5-fluorouracil in the assays with P. putida (EC50 = 0.027 mg/L) and P. subcapitata (EC50 = 0.11 mg/L), although cisplatin and doxorubicin were the most toxic to D. magna (EC50 = 0.64 and 2.0 mg/L, respectively). These two chemicals were also the most genotoxic in the SOS-chromotest (minimum genotoxic concentrations [MGC] = 0.07-0.2 mg/L), and 5-fluorouracil was the most genotoxic in the eukaryotic yeast assay (MGC = 0.02 mg/L). Our investigation seems to indicate generally lower risks of acute effects at concentrations expected in the environment. However, some effective concentrations were relatively low and chronic toxicity of cytostatics (and/or their transformation products), as well as specific sources of human pharmaceuticals such as hospital effluents, require research attention. PMID- 17867891 TI - Activated carbon amendment as a treatment for residual DDT in sediment from a superfund site in San Francisco Bay, Richmond, California, USA. AB - Pesticide formulators formerly operating at Lauritzen Channel, a portion of San Francisco Bay near Richmond (CA, USA), caused contamination of sediment with dichlorodiphenyltrichloroethane (DDT). The present study evaluated the distribution of residual DDT in channel sediment six years following extensive remedial dredging. High DDT concentrations (up to 252 mg/ kg) were found in Young Bay Mud sampled across the channel. Particle analyses showed most of the contamination is contained in the clay/silt sediment fraction, and desorption tests showed that availability is greater for DDT metabolites than parent DDT. The present study examined the feasibility of using activated carbon amendment to sequester DDT from sediment, including an evaluation of reactivated carbon as a less costly alternative to virgin activated carbons. Treatment success of activated carbon amendment to sediment collected from Lauritzen Channel was measured by reductions in aqueous equilibrium concentrations and uptake in semipermeable membrane devices (SPMDs). Four different activated carbons were tested and, after one month of treatment with 3.2 weight % carbon, DDT aqueous equilibrium concentrations were reduced up to 83% and SPMD uptake was reduced up to 91%. Reactivated carbon was comparable with virgin carbons in all tests. Reduction in SPMD uptake of DDT by treatment with 3.2% reactivated carbon increased to 99% after 26 months of treatment. The effectiveness of activated carbon was dependent on the type, size, dose, and contact time. The results show the potential usefulness of activated carbon amendment as a follow-up remedial technology for management of residuals after dredging contaminated sediment. PMID- 17867892 TI - Contaminant effects on host-parasite interactions: atrazine, frogs, and trematodes. AB - The effects of contaminants on multispecies interactions can be difficult to predict. The herbicide atrazine is commonly used in North America for corn crops, runs off into wetlands, and has been implicated in the increasing susceptibility of larval frogs to trematode parasites. Using experimental challenges with free living stages of trematodes (cercariae), it was found that Rana sylvatica tadpoles exposed to 30 microg/L of atrazine had significantly higher intensity of parasitism than did larval frogs either not exposed or exposed to 3 microg/L of atrazine. This result could not be explained by high concentrations of atrazine diminishing antiparasite behavior of tadpoles. Furthermore, when tadpoles and cercariae both were exposed to the same concentration of atrazine, either 3 or 30 microg/L, the abundance of formed cysts was not different from the condition in which both were housed at 0 microg/L of atrazine. Atrazine appears to be debilitating to both free-living cercariae and tadpoles. Studies examining relations between parasitism and contaminant levels must account for such combined effects as well as influences on other interacting species (e.g., first intermediate snail hosts). PMID- 17867893 TI - Effects of a fertilizer, an insecticide, and a pathogenic fungus on hatching and survival of bullfrog (Rana catesbeiana) tadpoles. AB - We assessed the single and interactive effects of ammonium nitrate fertilizer, the insecticide carbaryl, and a widespread waterborne pathogen Saprolegnia ferax on the hatching and survival of bullfrog (Rana catesbeiana) tadpoles in the laboratory. Carbaryl significantly reduced tadpole survival and hatching rate, but no interactive effects were found among stressors. PMID- 17867895 TI - A noninvasive test of exposition to toxicants: quantitative analysis of cytochrome P4501A expression in fish scales. AB - Elevated expression of cytochrome P4501A (CYP1A) is an established biomarker for exposition to a wide range of toxicants, particularly for dioxin and structurally similar compounds. Expression of CYP1A usually is analyzed in internal organs, which involves dissection of the specimen. To avoid unnecessary animal killing, we present here an alternative method based on the monitoring of CYP1A expression in fish scales. Using beta-naphthoflavone (BNF; 50 mg/kg body wt, intraperitoneal injection) as inducer in goldfish (Carassius auratus), we monitored levels of CYP1A mRNA both in scales and liver of treated and control specimens. Treatment with BNF resulted in a similar induction of CYP1A gene in both tissues, although scales responded faster (at 8 h after treatment) than liver (between 24 and 48 h). The scale-based test has the unique advantage of allowing sequential testing in the same specimen, which facilitates analysis of the time course of CYP1A induction and allows the study of individual variability. The method implies minimal suffering of the animals, because it only requires removal of a moderate (n = 1-3) number of scales for each time point. This nondestructive, fast, and relatively inexpensive test for toxic exposure therefore is suitable for environmental monitoring and food safety control programs in which specimen preservation is required. PMID- 17867896 TI - Evaluation of laboratory assays for the assessment of leaching of copper and chromium from ground-contact wood. AB - Laboratory studies were conducted to assess the leaching of Cu and Cr from wood, treated with a Cu-Cr-B preservative, when placed in contact with soil. Two laboratory assays were performed: Wood in contact with soil solutions over 30 d, and wood in direct contact with soil over 30 weeks. The influence of several factors, such as soil type and fertilizer use, was studied in both assays. In addition, the effect of soil moisture content and temperature was evaluated when wood was in contact with soil. A discrepancy in the results of the laboratory assays was observed. Leaching of Cu and Cr increased when soil in contact with wood was fertilized, but only an increase of Cu leaching was observed when soil solutions from fertilized soils were used. Moreover, soil solutions from a sandy clay loam soil produced a higher Cu leaching than those from a loamy sand soil, whereas the contrary occurred when treated wood was in direct contact with these soils. In the assay of treated wood in ground contact, the highest metal losses were produced in fertilized soils maintained at constant temperature and high soil moisture content, the latter being the most important factor. These losses were in the range of 5.34 to 15.6% for Cu and 1.85 to 2.35% for Cr in the soils studied. The proposed laboratory assay, using treated wood in direct contact with soil at a moisture content near field capacity during a period of 30 weeks, produced total metal losses that were in accordance with those reported by other authors under field conditions, expressed on a per-year basis. PMID- 17867897 TI - [Metabolic alterations, AIDS and vascular disease]. PMID- 17867898 TI - [Lipid profile in untreated HIV positive patients. HIV infection: cardiovascular risk factor?]. AB - INTRODUCTION: Some cases of HIV+ patients with unexplained vascular disease have been reported and many studies are being performed to determine whether HIV infected individuals have an increased cardio-vascular risk (CVR). We propose: to describe lipid profile of untreated HIV+ patients and to compare it with the HIV- and to assess whether any of the lipid abnormalities influence in CVR estimation. MATERIAL AND METHODS: 407 homosexual males: 251 untreated HIV+ and 156 HIV-. Biochemistry parameters: Total cholesterol (CHOL), HDL-cholesterol (HDL), VLDL cholesterol, LDL-cholesterol (LDL), triglycerides (TG), apolipoproteins A1 and B (ApoA1 y ApoB) and lipoprotein A. Atherogenic rates: CHOL/HDL, LDL/HDL and log (TG/HDL). HIV+ patients were classified into three groups according to CD4 lymphocytes number. RESULTS: HIV+ patients had lower CHOL, HDL, and ApoA1 and higher CVR rates. These differences showed also between each HIV+ group according to CD4 number and control group HIV-. 76% of the HIV+ patients showed low levels of HDL (less than 40 mg/dL) as compared with 31% of HIV- subjects. CONCLUSION: Untreated HIV+ patients' lipid profile is different from the HIV- subjects; one. There are decreases in HDL and ApoA1 from the beginning of the infection that persis along all the CD4 levels. HDL decrease in HIV infection multiplies global CVR in HIV infected individuals, independently of other risk factors. PMID- 17867899 TI - [Sex influence in lipodystrophy of HIV-infected patients and its association with cardiovascular risk factors]. AB - OBJECTIVE: To evaluate the influence of sex in human immunodeficiency virus (HIV) infected patients with lipodystrophy and its association with cardiovascular risk factors. PATIENTS AND METHOD: A cross-sectional study was conducted in HIV infected patients aged 20 or over managed at the outpatient Infectious Disease Unit in 2003. Clinical and epidemiological characteristics of HIV infection, lipodystrophy and cardiovascular risk factors were evaluated. RESULTS: Of the 760 patients included in the study, women comprised 28%. Men with lipodystrophy had a higher prevalence of hypertension, hypercholesterolemia, hypoalphalipoproteinemia and hypertriglyceridemia than those without lipodystrophy. Women with lipodystrophy had a higher prevalence of central obesity and hypertriglyceridemia compared with those without lipodystrophy (22.8 vs. 11.2%, p = 0.000; 20.6 vs. 9.3%, p = 0.001; 39.7 vs. 30%, p = 0.03 y 56.6 vs. 40.9%, p = 0.0001, respectively). The lipoatrophy pattern was predominant in men (24.9 vs. 12.6%, p = 0.0001) and lipoaccumulation forms in women (12.3 vs. 22.6%, p = 0.0001). Furthermore, women were younger, had a higher prevalence of smoking, family history of premature coronary heart disease and central obesity, and a lower prevalence of hypertension and hypoalphalipoproteinemia than men with lipodystrophy (42.1 +/- 8 years vs. 44.8 +/- 9.9 years, p = 0.03; 77.5 vs. 64%, p = 0.04; 22.5 vs. 9%, p = 0.003; 31 vs. 8.5%, p = 0.0001; 9.9 vs. 22.8%, p = 0.01; 25.4 vs. 39.7%, p = 0.03). CONCLUSIONS: This study demonstrated that the influence of sex in lipodystrophy in HIV-infected patients affects not only the lipodystrophy pattern, but also the cardiovascular risk profile. PMID- 17867900 TI - [Adequancy of the pharmacological disponibility in a Department of Internal Medicine to the WHO essential drug list]. AB - INTRODUCTION: Since several years ago, the World Health Organization (WHO), publishes the Essential Drug List (EDL) including medicines that are used to cover the mayor health community problems. Drugs are selected in terms of importance, usefulness, safety and cost-effectiveness. There is no enough data about adequacy between this list and the current medical practise in Internal Medicine. MATERIAL AND METHODS: Both EDL (13 edition, reviewed on April 2003) and the list of medicines used in the Internal Medicine Department from the Hospital da Barbanza, Riveira, A Coruna (Spain), Fundacion Publica del Servizo Galego de Saude in 2004-2005 were compared. RESULTS: From the 27 groups included in the EDL, 2 groups were excluded because no regular use in Internal Medicine. Among the other 25 groups there were significant differences in 24 groups. Just in one group both lists were identical. In all the 24 groups with differences, we used an smaller amount of drugs that recommended in the EDL. We analysed 15 groups (the groups with at least 5 differences between both lists). Causes identified were as follows: drugs used in diseases that we used to send to another hospital (Reference Hospital) in groups 6,8 and 12; drugs not commonly prescribed in Internal Medicine in groups 1,4,13,14,18,19 and 21, and finally drugs not currently financed by the National Health System (group 27). CONCLUSIONS: After examining the adequacy of the list of drugs prescribed in Internal Medicine in a Community Hospital we conclude that its use is significantly lower than the standard recommendations derived from de WHO. Identified causes are treatments not covered in a Community Hospital needing to transfer patients to another hospital and the inclusion of drugs not commonly used in Internal Medicine. The WHO estimates that over 2000 million people can not currently access to essential drugs nor vaccines all over the world. The problem is not just a health problem but also a social, economic and ethic one. So, an accurate use of such essential drugs in developed Health Systems could be a good example of efficiency. PMID- 17867901 TI - [Unfrequently opportunistic infection in lupus erythematosus with inmunosuppresive treatment]. AB - We present a case of systemic lupus erythematosus complicated by pancytopenia and visceral leishmaniasis in Spain. The literature on opportunistic infection in lupus erythematosus is reviewed.Leishmaniasis is a group of infections caused by the protozoa Leishmania, which is endemic in the Mediterranean basin. These opportunistic infections are an emerging entity in immunosuppressed patients. The use of immunosuppressive treatment in systemic lupus erythematosus modifies natural defense patterns and increases the risk of visceral leishmaniasis in endemic areas. PMID- 17867902 TI - [Liposarcoma histologic subtypes: four cases reports]. AB - The liposarcoma is a malignant tumor of mesodermic origin derived of the adipose tissue. Liposarcoma s types, according to his histological diagnosis, are: mixoide, pleomorphic, well differentiated and dedifferentiated. It can get to reach enormous proportions, mainly when it is located at abdominal level. His treatment is the radical surgery, it is possible, together with radiation therapy and/or chemotherapy. Four patients diagnosed of liposarcoma are shown up, a case of liposarcoma well differentiated, another case of liposarcoma pleomorphic and two cases about liposarcoma mixoide; with the characteristic that one of these two cases presented a local recidivation with a dediferenciation of itself. The evolution of the four cases, was in a different way. So, their prognosis is going to depend on their histopathologic variety and on a possible multicentricidad that is going to difficult the complete radical surgical exeresis. PMID- 17867903 TI - [Crohn s disease: is still the reason of fever of unknown origin?]. AB - We present two patients with Crohn's disease who presented with fever unknown origin, and mild intestinal symptoms. In case 1, the debut was with intermittent fever and symmetrical polyarthritis of the wrists, elbows, ankles and knees; in the case 2, prolonged fever associated to unspecific colicky abdominal pain. The initial approach was fever unknown origin yielded no etiology in both of them. The barium studies of the intestinal tract of paramount importance to reach a positive diagnosis in both cases. We strongly recommend the use of barium studies as a first line diagnostic tool in the approach of fever unknown origin. PMID- 17867904 TI - [Lipoid pneumonia related to an accidental aspiration of gas-oil]. AB - A 35-year-old non smoker man with no known history of chronic pulmonary disease, was treated at our hospital after accidental aspiration of gas-oil. He had developed an acute lipoid pneumonia in a few hours. Computed tomography of the chest showed a ground-glass pattern in middle lobe; given the immediate epidemiological precedent, it was possible to confirm a definitive diagnosis. One year later the patient is asymptomatic although small signs of acute process remain in the computed tomography. PMID- 17867905 TI - [Fournier's gangrene. Current perspectives]. AB - The Fournier Gangrene (FG) is a synergistic, polymicrobial, necrotizing fasciitis with infectious origin that produces gangrene of the perineal, genital or perianal skin. The number bigger than cases happens between 20 at 50 years, the males are affected more than the females in proportion 10:1 and the mortality rate is high yet. The clinical manage of the GF must be fast and opportune with intravenous application of fluids, electrolytes and systemic broad-spectrum antibiotic therapy; and avoid the hemodynamic stabilization of the patient before the surgery. The precocious surgery with debridement of the necrotizing tissues constitutes the main objective of the treatment. PMID- 17867906 TI - [Medicine and literature in the training of a house physician an internal medicine]. AB - Medical humanities are inseparable from the clinical activity. The aim of this paper is to demonstrate that evidence-based medicine and humanitary medicine based on narratives and values must be necessarily en effectively joined. It is detailed the utility of literature in the training of a house physician in internal medicine and it is exposed as methodology a complementary learning program about medicine and literature. Literary works are able to do from a reader physician, a "better physician". PMID- 17867907 TI - [Influence of the diabetes mellitus in the subjects with chronic obstructive pulmonary disease in setting ambulatory]. PMID- 17867908 TI - Inter-annual associations between precipitation and human incidence of West Nile virus in the United States. AB - Higher-than-average precipitation levels may cause mosquito outbreaks if mosquitoes are limited by larval habitat availability. Alternatively, recent ecological research suggests that drought events can lead to mosquito outbreaks the following year due to changes in food web structure. By either mechanism, these mosquito outbreaks may contribute to human cases of West Nile Virus (WNV) in the recent United States outbreak. Using countylevel precipitation and human WNV incidence data (2002-2004), we tested the impacts of above and below-average rainfall on the prevalence of WNV in human populations both within and between years. We found evidence that human WNV incidence is most strongly associated with annual precipitation from the preceding year. Human outbreaks of WNV are preceded by above-average rainfall in the eastern United States and below-average rainfall in the western United States in the prior year. While no direct mechanism may be determined from this study, we hypothesize that differences in the ecology of mosquito vectors may be responsible for the opposite relationships between precipitation and WNV outbreaks between the eastern and western United States. PMID- 17867909 TI - Isolation and establishment of the raccoon Ehrlichia-like agent in tick cell culture. AB - Feral animals are reservoirs of emerging human pathogens, as well as carriers of closely related wildlife diseases. The latter may interfere with epidemiologic studies by inducing cross-reactive antibodies, or by providing false positive signals in PCR based tests. We cultured a novel intracellular bacterium from the blood of two raccoons (Procyon lotor): RAC413 and RAC414. RAC413 had been experimentally inoculated with blood from a wild-caught raccoon, and provided the material for a blood passage into RAC414. The microbes grew in Ixodes scapularis (black-legged tick) cells, line ISE6, inoculated either with the leukocyte or erythrocyte fraction of anticoagulated blood. Giemsa-stained cells sampled two and three months after initial inoculation of the cultures revealed inclusions similar to those of Ehrlichia sp., except that individual bacteria commonly were elongated and clustered within endosomes. Electronmicroscopy confirmed the presence of irregularly shaped bacteria with evenly granular bacterioplasm bounded by a unit membrane. 16S rDNA sequencing identified the microbes as the raccoon Ehrlichia-like agent previously detected in feral raccoons from Georgia, United States. In conclusion, the availability of a culture isolate of this agent will facilitate future studies to determine its biology, epidemiologic significance, vector association, and host range. The Ehrlichia-like agent infecting raccoons joins a growing list of tick-borne agents cultivable in tick cells. PMID- 17867910 TI - Electrical therapy for advanced heart failure: is it time for a multidisciplinary approach or a new subspecialty? PMID- 17867913 TI - Candesartan: from left ventricular hypertrophy to heart failure, a global approach. AB - Cardiovascular disease is a continuum, starting with risk factors resulting from physiological changes and extending to vascular pathology associated with adverse clinical outcomes. The overactivation of the renin-angiotensin-aldosterone system has been related to the development and worsening of risk factors associated with cardiovascular diseases such as hypertension and heart failure. Treatment at each stage along the continuum may prevent, or at least delay, the next one, and so it is crucial to initiate therapy as early as possible in such patients so as to provide optimal care. Candesartan, a long-acting angiotensin receptor antagonist, has been shown to be an effective, and well-tolerated therapy, in both the early and late phases of cardiovascular disease (prehypertension, hypertension, left ventricular hypertrophy and heart failure). This article reviews the data supporting the use of candesartan in cardiovascular medicine, with a focus on left ventricular hypertrophy and ultimately heart failure. Particular emphasis is given to the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program, which has shown a positive impact of candesartan in patients with chronic heart failure in terms of reducing the incidence of cardiovascular deaths and chronic heart failure hospitalizations. PMID- 17867914 TI - Aliskiren, the future of renin-angiotensin system blockade? AB - The suppression of the renin-angiotensin system by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers has been proven in many studies to treat hypertension and reduce cardiovascular events; however, reducing angiotensin I receptor stimulation results in the loss of the negative-feedback signal, leading to increased plasma renin activity. Numerous direct renin inhibitors were synthesized, but abandoned owing to low potency, poor bioavailability and short half-life. Aliskiren, a direct renin inhibitor of a novel structural class, inhibits the activity of the renin produced and, thus, its capacity to form angiotensin I, as measured by plasma renin activity. Aliskiren has been recently shown to be efficacious in hypertensive patients at once-daily oral dosing with favorable pharmacokinetics and the potential to improve end-organ protection. PMID- 17867915 TI - ExTRACT-TIMI 25 trial: clarifying the role of enoxaparin in patients with ST elevation myocardial infarction receiving fibrinolysis. AB - Pharmacologic reperfusion remains the most common treatment strategy for ST elevation myocardial infarction (STEMI) worldwide. Unfractionated heparin (UFH) is the established adjunctive antithrombotic agent used with fibrinolytic agents. Low-molecular-weight heparins (LMWHs) are a potential alternative to UFH, but have not been evaluated in large cohorts of patients. The Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment (ExTRACT) Thrombolysis in Myocardial Infarction (TIMI) 25 was a double-blind, double-dummy randomized controlled trial, of 20,479 patients, which demonstrated the superiority of enoxaparin over UFH in reducing death or nonfatal myocardial infarction (MI) at 30 days, with an increase in major bleeding. The composite of death, nonfatal MI and nonfatal intracranial hemorrhage, was reduced with enoxaparin. Elderly patients (> or = 75 years of age) received a novel enoxaparin dosing regimen and when compared with UFH, benefited from a lower relative bleeding risk than younger patients without compromising efficacy in preventing death or MI. Intracranial hemorrhage rates were similar. The net clinical benefit of enoxaparin over UFH was maintained regardless of whether patients were on clopidogrel or not, or whether percutaneous coronary intervention was performed. Enoxaparin is an appropriate choice for adjunctive therapy with fibrinolysis in patients with STEMI. PMID- 17867916 TI - Pregnancy and adult congenital heart disease. AB - Increasing numbers of women with complex congenital heart disease are reaching childbearing age. Pregnancy is a major issue in the management of adult congenital heart disease. Cardiac disease is one of the most common causes of maternal morbidity and mortality. Complications, such as growth retardation, preterm and premature birth and even fetal and neonatal mortality, are more frequent among children of women with congenital heart disease. The risk of complications is determined by the severity of the cardiac lesion, the presence of cyanosis, the maternal functional class and the use of anticoagulation. However, the pathophysiology of these complications is not completely understood and may be related to a diminished increase in cardiac output and/or endothelial dysfunction. The management of pregnant cardiac patients is based on limited clinical information. This article reviews pre-pregnancy counseling and management during pregnancy in patients with congenital heart disease. PMID- 17867917 TI - Anatomy of coarctation, hypoplastic and interrupted aortic arch: relevance to interventional/surgical treatment. AB - Obstructive lesions in the aortic arch are comprised of discrete coarctation, tubular hypoplasia and interruption. This review discusses the anatomy of the lesions relevant to interventional treatment. Catheter intervention, using not only balloon angioplasty but also stent implantation for coarctation, has been developed over the past couple of decades as an alternative treatment to surgery. Several studies have reported long-term outcome and the benefits of surgery and catheter intervention for treating obstructive lesions in the aortic arch but more studies are needed for comparable evaluations. The development of imaging and further improvement of surgical and catheter intervention, such as hybrid intervention or new devices, will help in removing the obstruction safely. PMID- 17867918 TI - Patent foramen ovale closure: past, present and future. AB - Patent foramen ovale (PFO) is a common congenital abnormality that has been implicated in a number of disease processes, including cryptogenic stroke and migraine headaches. Medical treatment for these processes is often considered inadequate and mechanical closure of the PFO is an attractive, albeit controversial, alternative. PFO closure has become common practice in many centers, although recent guidelines limit its indication to certain subsets of patients. This review first focuses on the anatomy, physiology and pathophysiology of PFO, and then reviews the currently available and experimental devices for PFO closure, as well as the present clinical data pertaining to them. Finally, we present our perspective of the PFO closure, with regard to its current use and future directions. PMID- 17867919 TI - Stenting the neonatal arterial duct. AB - Ductal stenting in neonates with either duct-dependent pulmonary or systemic circulation has become a good alternative for the initial palliation of complex congenital heart disease. Changes of stent and catheter technology (low profile, flexible, premounted stents with good scaffolding), better patient selection and preparation, optimal interventional access and covering the complete length of the duct have significantly improved results. PMID- 17867920 TI - Role of image-guided vascular intervention in therapeutic angiogenesis translational research. AB - Therapeutic angiogenesis, the process of growing collateral blood vessels to better perfuse ischemic tissue, has been hailed as an up-and-coming treatment for symptomatic lower-extremity peripheral arterial occlusive disease. A minimally invasive durable treatment would be welcome since current treatment options for this disease carry high risk, limited efficacy or limited durability. Unfortunately, as evidenced by disappointing results in multiple clinical trials, therapeutic angiogenesis has yet to deliver in humans the success it has seen in animal models. In this review, we discuss the challenges of translating therapeutic angiogenesis into effective clinical treatments for lower-extremity peripheral arterial occlusive disease and we highlight the role that experts in image-guided vascular interventions can play in advancing the field. PMID- 17867921 TI - Contrast-enhanced intravascular ultrasound: combining morphology with activity based assessment of plaque vulnerability. AB - Acute coronary syndromes are the result of coronary plaque rupture in the majority of cases. Available diagnostic techniques that focus on the early detection of plaques that are prone to rupture are still limited. Increased neovascularization in the vasa vasorum of the atherosclerotic plaque has been identified recently as a common feature of inflammation and plaque vulnerability. Microbubbles, which have been used for ultrasound imaging, can be used to trace neovascularization. We present recent advances in contrast agents and contrast enhanced intravascular ultrasound that may be used for the detection of vasa vasorum, including fundamental and harmonic contrast imaging. Identification of vasa vasorum proliferation in atherosclerotic plaques presents important clinical implications; in particular it could provide a means to detect vulnerability in vivo, thereby guiding targeted treatments. PMID- 17867922 TI - In vivo wall shear stress measurements using phase-contrast MRI. AB - There is growing evidence to suggest that endothelial biology and atherosclerosis depend on arterial wall shear stress (WSS). We review the existing literature on in vivo measurements of WSS in healthy individuals using phase-contrast MRI, which is a promising, noninvasive technique for determining various blood flow characteristics. WSS data exist for the following arteries: carotid, brachial, aorta and femoral. Measured values indicate that WSS is site specific, a finding which opposes the notion that physiological WSS values are maintained at a constant magnitude in all parts of the arterial system. Among the WSS values obtained at the same site by different investigators there is qualitative agreement; however, differences exist in absolute values mainly due to the dependence on the method used to obtain WSS values from velocity data. PMID- 17867923 TI - Antiplatelet therapy in the era of drug-eluting stents: current and future perspectives. AB - The use of drug-eluting stents (DESs) dramatically reduced in-stent restenosis. However, the increasing use of these stents has raised concern about their potential thrombogenicity. Indeed, the particularity of DES thrombosis compared with bare metal stent thrombosis is a high rate of late thrombosis. Antiplatelet therapy is efficient in preventing DES thrombosis. However, this therapy could be optimized and may be improved in the future. This article will review the mechanisms and the epidemiology of stent thrombosis. Then, we will summarize the antiplatelet therapeutic strategies used to prevent stent thrombosis and especially DES-associated thrombosis. Finally, we will present some data with regard to potential advantages and pitfalls in DES thrombosis prevention using novel antiplatelet agents currently under development, as well as future stent designs with improved healing properties. PMID- 17867924 TI - Platelet function testing: state of the art. AB - Platelet function testing has evolved from crude tests, such as the bleeding time, to tests that permit a relatively sophisticated evaluation of platelet activity. Nonetheless, these tests are hampered by lack of specificity and sensitivity, and poor standardization of methods and techniques. The bleeding time, which has long been a staple of hemostasis testing, has been dropped from the test menu at many laboratories. In its place, tests such as the Platelet Function Analyzer-100 are increasingly used to screen patients with possible bleeding disorders. Older tests, such as platelet aggregometry and lumiaggregometry, are still used frequently because they provide insight into receptor, signaling pathway and granule release mechanisms. Flow cytometry is available in some specialized laboratories and allows for quantitative and qualitative assessment of some platelet functions, although the expense of testing is often prohibitive. Finally, the wider availability of platelet function testing has stimulated interest and demand for monitoring the effect of platelet inhibitory drugs, such as aspirin and clopidogrel. As platelet function pathways become better understood, the demand for these type of monitoring tests is likely to increase. PMID- 17867925 TI - Clinical implications of aspirin resistance. AB - Aspirin (acetylsalicylic acid) is one of the main therapeutic medications used in the prevention of thromboembolic vascular events. Aspirin exhibits its antiplatelet action by irreversibly inhibiting platelet cyclooxygenase-1 enzyme, thus preventing the production of thromboxane A2 (TXA2). Aspirin resistance, as measured in vitro, is the inability of aspirin to reduce platelet activation and aggregation by failure to suppress the platelet production of TXA2. Laboratory tests of platelet TXA2 production or platelet function dependent on TXA2 can detect aspirin resistance in vitro. The clinical implication of this laboratory definition has not yet been elucidated via prospective trials that have controlled for confounders, such as hypertension, diabetes and dyslipidemia. Large meta-analyses have found low-dose aspirin to be as effective as high-dose aspirin in preventing vascular events, making a dose-dependent improvement in laboratory response clinically irrelevant. Possible causes of aspirin resistance include poor compliance, inadequate dose, drug interactions, genetic polymorphisms of cyclooxygenase-1, increased platelet turnover and upregulation of non-platelet pathways of thromboxane production. However, there is currently no standardized approach to the diagnosis and no proven effective treatment for aspirin resistance. Further research exploring the mechanisms of aspirin resistance is needed in order to better define aspirin resistance, as well as to develop a standardized laboratory test that is specific and reliable, and can correlate with the clinical risk of vascular events. The intent of this paper is to review the literature discussing possible mechanisms, diagnostic testing and clinical trials of aspirin resistance and to discuss its clinical relevance as it pertains to cerebrovascular and cardiovascular disease. PMID- 17867926 TI - Catheter ablation for ventricular tachycardia: indications and techniques. AB - Ventricular tachycardia (VT) may be secondary to many different underlying pathophysiologies. The nature of the underlying disorder determines amenability to catheter ablation, thus, dictating the circumstances under which it should be undertaken. The differing substrates also influence the choice of techniques that are used. The most intensively studied clinical subgroup of VT is re-entrant VT in the setting of ischemic heart disease. The approach to ablation in such patients is discussed in detail. Subsequent discussion focuses on other clinically encountered varieties of VT and the ablation methods used in each individual disease state. PMID- 17867927 TI - Excitability of skeletal muscle during development, denervation, and tissue culture. AB - A quantitative understanding of the bulk excitability of skeletal muscle tissues is important for the design of muscle tissue bioreactor systems, implantable muscle stimulators, and other systems where electrical pulses are employed to elicit contractions in muscle tissue both in vitro and in vivo. The purpose of the present study is to systematically compare the excitability of mammalian (rat) skeletal muscle under a range of conditions (including neonatal development, denervation, and chronic in vivo stimulation of denervated muscle) and of self-organized muscle tissue constructs engineered in vitro from both primary cells and cell lines. Excitability is represented by rheobase (R(50), units = V/mm) and chronaxie (C(50), units = microseconds) values, with lower values for each indicating greater excitability. Adult skeletal muscle is the most excitable (R(50) ~ 0.29, C(50) ~ 100); chronically denervated whole muscles (R(50) ~ 2.54, C(50) ~ 690) and muscle engineered in vitro from cell lines (C2C12 + 10T1/2) (R(50) ~ 1.93, C(50) ~ 416) have exceptionally low excitability; muscle engineered in vitro from primary myocytes (R(50) ~ 0.99, C(50) ~ 496) has excitability similar to that of day 14 neonatal rat muscle (R(50) ~ 0.65, C(50) ~ 435); stimulated-denervated muscles retain excellent excitability when chronically electrically stimulated (R(50) ~ 0.40, C(50) ~ 100); and neonatal rat muscle excitability improves during the first 6 weeks of development, steadily approaching that of adult muscle. PMID- 17867928 TI - Engineered liver-like tissue on a capillarized matrix for applied research. AB - Liver tissue that is functional and viable for several weeks in vitro represents an auspicious test system for basic and applied research. In this study, a coculture system for hepatocytes (HCs) and microvascular endothelial cells (mECs) was generated applying tissue-engineering techniques, establishing the basis for a new bioartificial liver in vitro model. Porcine mECs were seeded on a decellularized porcine jejunal segment with preserved vascular structures. Porcine HCs were seeded onto this vascularized scaffold, and the resulting coculture was maintained for 3 weeks in vitro. Tissue morphology and differentiation was monitored using histology and immunohistochemistry. Tissue metabolism was monitored using daily assessment of urea and lactate production. HC monolayer cultures served as controls. The 2-stage seeding procedure resulted in a 3-dimensional coculture system harboring HC cell clusters in multiple cell layers lining the generated mEC-seeded capillary structures. It was viable for 3 weeks, and HCs maintained their morphology and differentiation. Biochemical testing revealed stable metabolic activity of the tissue culture. In contrast, HCs cultured in monolayer showed morphological dedifferentiation and an unfavorable metabolic state. Our mEC-HC coculture represents a new approach toward a functional bioartificial liver-like tissue applicable as a test system for basic and applied research. PMID- 17867930 TI - Gene set enrichment analysis reveals several globally affected pathways due to SKI-1/S1P inhibition in HepG2 cells. AB - Sterol regulatory element-binding proteins (SREBPs) are transcription factors governing transcription of genes related to cholesterol and fatty acid metabolism. To become active, SREBPs must undergo a proteolytic cleavage to allow an active NH(2)-terminal segment to translocate into the nucleus. SKI-1/S1P is the first protease in the proteolytic activation cascade of SREBPs. SREBP inhibition may be useful, for example, in the treatment of liver steatosis caused by homocysteine-induced lipid synthesis. Accordingly, we overexpressed inhibitory prodomains (proSKI) of SKI-1/S1P in HepG2 cells to block SREBP activation to evaluate the potential of SKI-1/S1P in controlling cellular cholesterol synthesis. SKI-1/S1P inhibition resulted in reduced cholesterol synthesis and mRNA levels of the rate-limiting enzymes, HMG-CoA reductase and squalene epoxidase, in the cholesterol synthetic pathway. The inhibitory effect was maintained in the presence of homocysteine-induced endoplasmic reticulum stress. A gene set enrichment analysis was performed to elucidate other metabolic effects caused by SKI-1/S1P inhibition. SKI-1/S1P inhibition was observed to affect a number of other metabolic pathways, including glycolysis and citric acid cycle. These results demonstrate that inhibition of SREBPs decreases cholesterol synthesis in HepG2 cells both in the absence and presence of homocysteine. SKI 1/S1P inhibition may cause widespread changes in other key metabolic pathways. PMID- 17867931 TI - Mitochondrial dysfunction: the first domino in brain aging and Alzheimer's disease? AB - With the increasing average life span of humans and with decreasing cognitive function in elderly individuals, age-related cognitive disorders including dementia have become a major health problem in society. Aging-related mitochondrial dysfunction underlies many common neurodegenerative disorders diseases, including Alzheimer's disease (AD). AD is characterized by two major histopathological hallmarks, initially intracellular and with the progression of the disease extracellular accumulation of oligomeric and fibrillar beta-amyloid (Abeta) peptides and intracellular neurofibrillary tangles (NFT) composed of hyperphosphorylated tau protein. In this review, the authors focus on the latest findings in AD animal models indicating that these histopathological alterations induce deficits in the function of the complexes of the respiratory chain and therefore consecutively result in mitochondrial dysfunction. This parameter is intrinsically tied to oxidative stress. Both are early events in aging and especially in the pathogenesis of aging-related severe neurodegeneration. Ginkgo biloba extract seems to be of therapeutic benefit in the treatment of mild to moderate dementia of different etiology, although the data are quite heterogeneous. Herein, the authors suggest that mitochondrial protection and subsequent reduction of oxidative stress are important components of the neuroprotective activity of Ginkgo biloba extract. PMID- 17867932 TI - The zero sum game. PMID- 17867933 TI - First prize: direct real-time temperature monitoring for laparoscopic and CT guided radiofrequency ablation of renal tumors between 3 and 5 cm. AB - PURPOSE: To evaluate our experience with radiofrequency ablation (RFA) of renal tumors in the range of 3 to 5 cm. PATIENTS AND METHODS: A series of 96 patients underwent 104 tumor laparoscopic or percutaneous CT-guided RFAs. We identified 37 tumors between 3 and 5 cm at the time of the ablation. Non-conducting temperature probes, independent of the radiofrequency (RF) electrode, were placed at the peripheral and deep margins of the tumor in order to achieve real-time temperature monitoring of the ablation zone. All ablations were continued until the peripheral and deep temperature probes reached 60 degrees C. RESULTS: All 37 patients (100%) achieved complete necrosis at the initial session. There were two radiographic failures at 9 months and 30 months that required a second treatment (95% radiographic success rate). Tissue samples taken at the time of the re treatment (one partial nephrectomy with numerous biopsies of the deep and peripheral margins and one repeat ablation with eight core biopsies) showed no evidence of viable tumor with hematoxylin and eosin or nicotinamide adenine dinucleotide viability stains. The average length of follow-up was 11.3 months (range 1-44 months). No patient with localized disease at the time of the RFA developed local extension or metastatic disease in follow-up. CONCLUSIONS: The majority of renal tumors between 3 and 5 cm can be ablated with complete necrosis in a single session. Placement of independent temperature probes at the peripheral and deep margins of the tumor provides real-time monitoring that assists in the deployments of the RF electrode and determining the appropriate duration of the ablation cycles. Attention to real-time thermometry decreases the need for repeat sessions to achieve complete necrosis for larger tumors. Likewise, real-time thermometry decreases the incidence of overtreatment of normal parenchyma and prevents collateral damage to adjacent vital structures (ureter, pancreas, bowel, spleen, nerves) outside the desired zone of ablation. PMID- 17867934 TI - Second prize: preliminary experience with the Niris optical coherence tomography system during laparoscopic and robotic prostatectomy. AB - PURPOSE: To evaluate the feasibility of high-resolution optical coherence tomography (OCT) in the identification of neurovascular bundles (NVBs) during laparoscopic and robotic radical prostatectomy (LRP). PATIENTS AND METHODS: Between November 2005 and March 2006, 24 patients undergoing transperitoneal laparoscopic or robotic radical prostatectomy were enrolled in this study. Once the bladder was taken down and the prostate mobilized, the Niris imaging system was deployed. In each patient, in-vivo images were obtained to determine the image characteristics of NVBs, adipose tissue, prostate capsule, and endopelvic fascia. The NVB was imaged again in vivo, after the prostate was excised. Ex-vivo images were obtained from the prostate surface to look for the presence or absence of the NVBs and correlated with the surgeon's assessment of the adequacy of nerve sparing. RESULTS: From 24 patients, we obtained more than 300 OCT images of tissue structures including endopelvic fascia, prostate capsule, NVBs, fat, lateral pedicles, and lymphatics. These images were found to correlate independently with the surgeon's impression of the tissue being imaged. Preliminary comparison with parallel histologic evaluation was performed in four patients that suggested OCT could help to identify the NVBs and prostate capsule during LRP. CONCLUSIONS: In our preliminary experience with the Niris system during LRP, OCT was able to image the NVB in all patients. This could enhance surgical precision during nerve sparing and positively impact potency rates after radical prostatectomy. Further research will be needed, including parallel histologic evaluation and follow-up, to validate the findings of OCT imaging. PMID- 17867935 TI - Second prize: frequency of benign renal cortical tumors and histologic subtypes based on size in a contemporary series: what to tell our patients. AB - BACKGROUND AND PURPOSE: Historically, 85% to 90% of renal masses have been malignant, with the majority being renal-cell carcinoma. However, with the increasing frequency of incidentally discovered renal masses, only 70% to 85% of lesions are found to be malignant. Furthermore, the pathologic breakdown of these lesions on the basis of size is not well described. This study sought to determine the incidence of the various histologic subtypes of renal cortical tumors according to size in a contemporary series of surgically treated patients. MATERIALS AND METHODS: Our prospectively collected database of all 482 patients who underwent partial or radical nephrectomy for a unilateral, unifocal, suspicious renal cortical tumor between January 2001 and October 2005 was reviewed. The frequency of benign and malignant lesions was determined according to size, as was the incidence of the various histologic subtypes. RESULTS: Of the lesions, 228 were 4 cm. Of all lesions 4 cm were benign. For larger lesions, 10.9% of those between 4 and 7 cm and only 5.6% of those >7 cm were benign (P < 0.001). A significant difference between histologic subtypes according to size also was found (P = 0.01). Smaller lesions (20 mg/dL, Gleason score = 8, and stage cT(2c) or higher), intraoperative criteria (difficulty separating the tissues around the prostate), and evidence of extracapsular extension (ECE) on magnetic resonance imaging. We performed unilateral partial resection, nerve advancement, and, finally, end-to-end anastomosis in six patients, whereas in one patient, we did a bilateral partial excision. We analyzed the results in terms of oncologic safety (positive surgical margins and PSA) and SHIM score after 18 months of follow-up. RESULTS: Pathologic examination revealed stage T3 disease in six patients; one had a positive surgical margin. Two patients are receiving salvage radiotherapy for PSA relapse, and five continue to have undetectable PSA concentrations after a median follow up of 20 months. Five of the seven men recovered erectile potency with or without a phosphodiesterase inhibitor, and their median SHIM score is 18. CONCLUSIONS: We are encouraged by the initial results of NAT. The procedure may be an alternative for men who require extensive NVB dissection. However, further experience, longer follow-up, and independent trials are necessary. PMID- 17867938 TI - Pelvic kidney: associated diseases and treatment. AB - The incidence of pelvic kidney has been approximated at between 1 in 2200 and 1 in 3000. The ectopic kidney is thought to be no more susceptible to disease than the normally positioned kidney, except for the development of calculi and hydronephrosis. Because of the greater risk of injuring aberrant vessels or overlying abdominal viscera and nerves, the pelvic kidney presents special treatment challenges. Alternative approaches to treating nephrolithiasis may yield better outcomes. The tortuous ureter often associated with a pelvic kidney hinders deflection of the flexible ureteroscope, potentially limiting access. Laparoscopy-guided intervention permits visual exposure of the kidney, enhancing safe puncture and tract placement integral to percutaneous nephrolithotomy. Laparoscopy-assisted anterior retrograde percutaneous nephroscopy involves percutaneous access using a Hunter-Hawkins retrograde nephrostomy needle with adjunctive laparoscopy to permit viewing and manipulation of overlying bowel. Ureteropelvic junction (UPJ) obstruction has been reported to occur in 22% to 37% of ectopic kidneys. Endoscopic incision presents difficulties beyond those of anatomically normal kidneys. The laparoscopic approach provides good surgical exposure, and operative times are comparable to those of laparoscopic pyeloplasty in anatomically normal kidneys. To date, only a handful of cases of malignancy in a pelvic kidney have been described. Like a nonfunctioning anatomically normal kidney, a nonfunctional pelvic kidney may require primary removal. There are a few reports of laparoscopic pelvic nephrectomy. Additional studies are needed to compare the various treatments for disease of the pelvic kidney in order to decide which options have the most beneficial outcomes. PMID- 17867939 TI - Durability of endourologic skills: two-year follow-up study. AB - PURPOSE: To assess the long-term durability of endourologic skills among urology trainees after an intensive technical skills training course. SUBJECTS AND METHODS: Seventeen urology residents participated in a 2-day ureteroscopy course at a surgical skills center. Residents performed rigid ureteroscopy and basket manipulation of a small midureteral stone. Performance was assessed immediately after the course and 1 year and 2 years after training. Residents prospectively tracked all ureteroscopic cases in which they were considered the primary surgeon (i.e., performed greater than 75% of the procedure). Performance was measured using a validated global rating score (GRS), checklist score (CLS), and time required to complete the task. RESULTS: Overall, GRS improved over the 2-year follow-up (P < 0.001), with most of the improvement occurring in the first year (P = 0.03). The CLS and time to complete the task did not change (P = 0.08 and 0.12, respectively). At the 2-year follow-up, the number of cases logged had no significant effect on performance. CONCLUSIONS: Ureteroscopy skills are retained and continue to improve 2 years after completing an intense training session that uses high-fidelity bench models. Ureteroscopic experience is important for the maintenance and development of skills, even though they appear to plateau after 1 year. This result may also reflect a ceiling effect of the assessment tools. PMID- 17867941 TI - Laparoscopic pyelolithotomy: indications and technique. AB - BACKGROUND AND PURPOSE: Laparoscopic pyelolithotomy, although uncommonly performed, may be considered in patients who have renal anomalies, are poorly compliant, and have a large single renal-pelvic calculus. We present our experience with this procedure in five patients. PATIENTS AND METHODS: Three patients underwent laparoscopic pyelolithotomy because of a horseshoe kidney, one for a pelvic kidney, and one for a large renal-pelvic calculus. All stones were solitary with a mean size of 2280 mm2 (range 540-8200 mm2). All were approached transperitoneally with passage of a flexible cystoscope through a laparoscopic port to aid in stone extraction. RESULTS: All cases were completed laparoscopically. The length of surgery was 74, 92, 134, 158, and 159 minutes. There were no minor or major complications, and the estimated blood loss was <50 mL in all cases. All patients were discharged on postoperative day 1 with the drains removed. Four patients were stented for 4 to 6 weeks. The remaining patient was not stented because of poor compliance. The stents were removed with office cystoscopy. All patients were stone free on follow-up imaging. CONCLUSIONS: Laparoscopic pyelolithotomy can be done safely, effectively, and efficiently with proper patient selection and adherence to standard laparoscopic surgical principles. PMID- 17867942 TI - Treatment of symptomatic caliceal diverticula using a mini-percutaneous technique with greater than 3-year follow-up. AB - BACKGROUND AND PURPOSE: Caliceal diverticula can be treated with a variety of techniques. Traditional percutaneous techniques utilize nephrostomy-tract dilation to between 26F and 32F. Identification of a small diverticulum can be difficult after such dilation. The mini-percutaneous nephrolithotomy technique has been described for the treatment of nephrolithiasis. We report on two patients with caliceal diverticula treated using a mini-perc technique with long term follow-up. PATIENTS AND METHODS: Two symptomatic patients underwent treatment of posterior caliceal diverticula using a mini-perc technique. An interventional radiologist placed an 8F nephrostomy tube for access to the diverticulum. The following day, a 12F/14F ureteral access sheath was placed over a guidewire. Through the sheath, we identified the diverticulum and its neck with a 7F semirigid ureteroscope. The diverticular neck was balloon dilated to 18F, followed by fulguration with a 3F Bugbee electrode. A Double-J ureteral stent was placed antegrade from the diverticulum to the bladder, and an 8F nephrostomy tube provided external drainage. RESULTS: The mean operative time was 138.5 minutes, and the mean estimated blood loss was 10 mL. Neither of the diverticula contained calculi. The mean length of stay was 2.5 days, and there were no complications. The hemoglobin and creatinine values showed no significant change. Both patients remained asymptomatic at a mean follow-up of 38 months. CONCLUSION: Treatment of a caliceal diverticulum via a mini-perc technique is safe, effective technique with durable long-term results. It offers a less-invasive alternative to standard percutaneous treatment with larger access sheaths. PMID- 17867943 TI - Comparison of graft survival in live donor nephrectomy: hand-assisted laparoscopic v open procedures. AB - PURPOSE: Laparoscopic donor nephrectomy is associated with decreased morbidity while maintaining similar graft function in short-term follow-up compared with open surgery. We investigated hand-assisted laparoscopic donor nephrectomy (HALDN) in comparison with standard open donor nephrectomy (ODN) in living donors. PATIENTS AND METHODS: Two hundred patients who received a living-donor kidney and were followed up for more than 1 year were enrolled. The procedure was performed exclusively on the left kidney through either HALDN or ODN from January 2001 to July 2004. The probability of graft survival was determined using the Kaplan-Meier method. Multivariate analysis using a Cox regression hazard model was performed to identify the predictors of graft survival. RESULTS: The mean operative time, estimated blood loss, warm ischemic time, and operation-related complications were compared. There was no difference in graft function. The cumulative graft survival at 1 and 3 years was similar in the two groups: 98% and 97%. Episodes of acute rejection were an independent predictor of graft survival. CONCLUSIONS: Hand-assisted laparoscopic nephrectomy in living donors is safe and effective with results similar to those of open nephrectomy with regard to graft function. PMID- 17867944 TI - Early laparoscopic management of acute postoperative hemorrhage after initial laparoscopic surgery. AB - BACKGROUND AND PURPOSE: The use of laparoscopic surgery has been well established for the management of abdominal emergencies. However, the value of this technique for postoperative hemorrhage in urology has not been characterized. We present our favorable experience with laparoscopic exploration after urologic surgery and suggest guidelines for laparoscopic management of post-laparoscopy bleeding. PATIENTS AND METHODS: Three patients who developed hemorrhage shortly after laparoscopic urologic surgery and were managed by laparoscopic exploration were identified from a series of 910 laparoscopic urologic procedures performed at our institution from October 2002 to June 2006. RESULTS: Three patients, who were hemodynamically stable (two after robot-assisted laparoscopic prostatectomy, one after laparoscopic radical nephrectomy), required prompt surgical exploration for postoperative hemorrhage not stabilized by blood transfusion (mean 2.7 units) at a mean of 19.4 hours after initial surgery. Clots were evacuated with a 10-mm suction-irrigator. Two patients were found to have abdominal-wall arterial bleeding and were managed with suture ligation. The third patient demonstrated diffuse bleeding from the prostatic bed, which was controlled with Surgicel and FloSeal. Bleeding was efficiently controlled in all patients, and none required post-exploration transfusion. The mean post-exploration hospital stay was 2.3 days. CONCLUSION: Significant hemorrhage after urologic laparoscopy is a rare event. We found laparoscopic exploration to be an excellent way to diagnose and correct such hemorrhage in certain patients. Early diagnosis with clinical and hematologic studies, a lowered threshold for surgical exploration, and specific operative equipment may decrease patient morbidity and the need for open surgical exploration. PMID- 17867945 TI - Laparoscopic partial nephrectomy in upper-pole apical renal tumor using gauze sling and flexible laparoscope. AB - Upper-pole apical renal tumors are difficult to see using conventional rigid laparoscopes during laparoscopic partial nephrectomy. Added to this, the instrument angle makes tumor excision and kidney reconstruction difficult. We therefore elevated the kidney using a gauze sling and observed the lesion through a flexible laparoscope. With a clear field of vision, we could excise tumors and repair the kidney more easily. PMID- 17867946 TI - Laparoscopic heminephrectomy for upper-pole moiety in children using a 3-mm laparoscope and instruments. AB - PURPOSE: We report three cases of laparoscopic heminephrectomy in infants using a 3-mm laparoscope and instruments. To our knowledge, this is the first pediatric heminephrectomy series reported in the literature that utilized these small instruments. PATIENTS AND METHODS: Three pediatric patients underwent laparoscopic heminephrectomy for an upper-pole moiety in a duplicated collecting system with 3-mm laparoscopic ports and a 3-mm Storz 30 degrees laparoscope. RESULTS: All three cases were completed laparoscopically with total times of 120, 135, and 160 minutes. There were no intraoperative complications, and there was minimal blood loss. The optics of the laparoscope provided visibility and illumination similar to those available with larger-diameter laparoscopes. Two patients were discharged approximately 1 day postoperatively. The third patient required intravenous antibiotics to treat a urinary-tract infection and was discharged home 4 days postoperatively. All three patients had recovered fully by 2 weeks. CONCLUSION: The 3-mm laparoscope provides excellent visibility and illumination for performing heminephrectomy in the pediatric population. In addition, the 3-mm instruments provide excellent tissue handling, similar to that of the 5-mm tools. PMID- 17867947 TI - Radiofrequency ablation of renal tumors improved by preoperative ex-vivo computer simulation model. AB - BACKGROUND AND PURPOSE: Radiofrequency ablation (RFA) of small renal tumors has emerged as an option for patients with contraindications to surgery. The technique usually is limited to dorsolateral tumors because of the unknown pattern of heat distribution. The aim of this in-vitro experiment was to develop a planning computer simulation model of the heat distribution in order to calculate needle placement correctly. MATERIALS AND METHODS: Our measurement system enables capture of the temperature pattern of a linear arrangement of thermocouples in a porcine cadaver kidney. A high-frequency sinusoidal electric current (460 kHz) was introduced via a unipolar umbrella-shaped needle electrode. The results of the RFA thermocoagulation were compared with the computer model using the finite element method. RESULTS: Comparison between ex-vivo simulation and in-vivo measurement of destruction in three porcine cadaver kidneys showed excellent agreement. The discoloring of the necrotic region represented a temperature of 42 degrees C, where the tissue begins to denaturate. The 42 degrees C isodose temperature could be simulated precisely starting 6 mm from the center of the needle electrode. Using several MATLAB programs, simulation models were created to predict the space and time correlation of the necrotic regions. CONCLUSION: This experimental model allows successful planning of the expected necrotic region using RFA in a cadaver kidney. Future planning can be improved by using a perfused in-vivo kidney model, thus allowing much more precise computer simulation before applying RFA to kidney tumors at critical locations. PMID- 17867948 TI - In-vitro renal shrinkage after hypertonic saline perfusion for organ removal during laparoscopic nephrectomy. AB - BACKGROUND AND PURPOSE: To evaluate the possibility of shrinking the kidney by perfusion with hypertonic solution to facilitate organ removal in laparoscopic surgery. MATERIALS AND METHODS: After 18 open nephrectomies (ONs) in 9 pigs, one of four saline solutions (5%, 7.5%, 10%, and 15%) was infused through a catheter into the renal artery for 5 minutes in four kidneys each. The volumes and weights of the kidneys were measured before and after renal perfusion; the kidneys were then sent for histologic evaluation. Eight ONs were performed, and the kidneys were removed from the abdominal cavity in a plastic bag in order to mimic organ entrapment during laparoscopy. The kidneys were perfused with hypertonic solution and were again put in a plastic bag and removed from the same animal's abdomen through another incision. The incisions were measured with calipers before and after extraction of the unperfused and perfused organs. RESULTS: The kidneys that underwent perfusion with 5% saline had the greatest decrease in both weight and volume, an average of 16% and 17.8%, respectively. The average incision needed for extraction of unperfused kidneys was 44.9 mm (range 40-58 mm), whereas the mean size of the incision needed to remove perfused kidneys was 26.6 mm (range 20 30 mm) (P < 0.001). The relative reduction in the necessary incision size therefore was 44.3% (range 33.3%-55%). CONCLUSION: Perfusion with 5% saline is able to shrink the kidney volume slightly with mild histologic changes. In the pig, it is possible to decrease the renal incision necessary for kidney removal by 44% using this method. PMID- 17867949 TI - Laparoscopic pyeloplasty compared with open pyeloplasty in children. AB - BACKGROUND AND PURPOSE: Open dismembered pyeloplasty by a retroperitoneal approach remains the reference standard for correcting ureteropelvic junction (UPJ) obstruction in children. We prospectively compared the results of laparoscopic and open pyeloplasty in children with UPJ obstruction. PATIENTS AND METHODS: During the period April 2003 to March 2005, 15 children underwent laparoscopic pyeloplasty and 14 children underwent open pyeloplasty. The two groups were similar in age and mean weight. We prospectively analyzed and compared operative time, postoperative pain and activity, complications, and hospital stay in the two groups. The mean follow-up was 23 and 24 months in the laparoscopy and open surgery group, respectively. RESULTS: The mean operative time was significantly shorter in the open surgery group (159 +/- 21.39 [SD] v 214 +/- 32.26 minutes; P = 5.874 x 10(-6)). Postoperative discomfort/pain on day 7 was significantly less in the laparoscopic group, and the mean hospital stay was significantly shorter (P = 0.018019). CONCLUSIONS: The benefits of laparoscopic pyeloplasty include a high reproducible success rate comparable to the results achieved by open pyeloplasty. Our results indicate minimal morbidity such as pain and a quick return to normal activities. The hospital stay is significantly reduced, although the operative times are long compared with open pyeloplasty. PMID- 17867950 TI - Comparison of ethanol and sodium tetradecyl sulfate in the sclerotherapy of renal cyst. AB - BACKGROUND AND PURPOSE: Renal cysts are common in the adult population. Symptomatic cysts traditionally have been treated by percutaneous aspiration with injection of sclerosant agents. Our aim was to compare the efficacy and side effects of ethanol and sodium tetradecyl sulfate (STDS) as sclerosants for symptomatic simple renal cyst. PATIENTS AND METHODS: Sixty-five patients with 68 symptomatic simple renal cysts were included in this study. An 8F pigtail catheter was inserted into the cyst under ultrasound guidance followed by aspiration of the cyst fluid. Either 95% ethanol (N = 34) or 3% STDS (N = 34), assigned randomly, was then instilled into the empty sac. Patients recorded any flank pain on a visual analog scale and were followed up by ultrasonography for 6 to 18 months. RESULTS: There was complete ablation of 28 (82%) and 26 (76%) cysts, partial regression of 3 (9%) and 6 (18%) cysts, and failure of treatment in 3 (9%) and 2 (6%) cysts in the ethanol and STDS groups, respectively. There was no major complication in either group. The pain caused by the injection was significantly less for the group receiving STDS (pain score 2.1 +/- 1.1 v 3.8 +/- 1.2 for ethanol; P = 0.019). CONCLUSIONS: Ethanol and STDS are simple, noninvasive, cost-effective, and well-tolerated sclerosants for the treatment of simple renal cysts. We prefer STDS as a first choice because it causes less pain. PMID- 17867951 TI - Determination of ideal stent length for endourologic surgery. AB - PURPOSE: To assess whether direct measurement of ureteral length correlates with patient height or the ureteral length measured on intravenous urography in order to determine the appropriate ureteral stent length to be used for ureteroscopic surgery. PATIENTS AND METHODS: Sixty-five patients (70 ureters) who underwent ureteroscopic procedures were evaluated. The ureteral length between the ureteropelvic and ureterovesical junctions was determined either by preoperative intravenous urography (straight ureteral length; SUL) or intraoperatively with the aid of a guidewire (practical ureteral length; PUL). We regarded the PUL as a clinically useful measurement. The height, SUL, and PUL for each patient was determined. For a postoperative comparison of proper stent position, we selected another 36 patients in whom the length of the stent was based on patient height. RESULTS: The SUL values correlated significantly with the PUL (R2 = 0.482 on the right v 0.564 on the left side) and might be used as a predictor of stent length. However, patient height did not correlate with the PUL. Postoperative stent position tended to be better in the patients who had direct ureteral measurements than in those with stents chosen on the basis of patient height. CONCLUSION: Determination of stent length according to patient height does not correlate well with the length needed for endoscopic procedures. Direct measurement of the ureteral length is easy and minimizes stent-associated complications and stent migration. PMID- 17867952 TI - Development of miniaturized light endoscope-holder robot for laparoscopic surgery. AB - PURPOSE: We have conducted experiments with an innovatively designed robot endoscope holder for laparoscopic surgery that is small and low cost. MATERIALS AND METHODS: A compact light endoscope robot (LER) that is placed on the patient's skin and can be used with the patient in the lateral or dorsal supine position was tested on cadavers and laboratory pigs in order to allow successive modifications. The current control system is based on voice recognition. The range of vision is 360 degrees with an angle of 160 degrees . Twenty-three procedures were performed. RESULTS: The tests made it possible to advance the prototype on a variety of aspects, including reliability, steadiness, ergonomics, and dimensions. The ease of installation of the robot, which takes only 5 minutes, and the easy handling made it possible for 21 of the 23 procedures to be performed without an assistant. CONCLUSION: The LER is a camera holder guided by the surgeon's voice that can eliminate the need for an assistant during laparoscopic surgery. The ease of installation and manufacture should make it an effective and inexpensive system for use on patients in the lateral and dorsal supine positions. Randomized clinical trials will soon validate a new version of this robot prior to marketing. PMID- 17867953 TI - Hem-o-lok clips to control both the artery and the vein during laparoscopic nephrectomy: personal experience and review of the literature. AB - BACKGROUND AND PURPOSE: Control and division of the renal vessels is a critical step in laparoscopic nephrectomy. Although the linear cutting stapler is easy to use, a 1.7% malfunction rate has been reported, and the consequences of this failure can be serious, including often-emergency conversion to an open procedure and even death. We reviewed the purely laparoscopic nephrectomies performed in our center, in which both the renal artery and the vein were secured using only nonabsorbable polymer ligating (NPL) clips. Our purpose was to evaluate the reliability, safety, and cost-effectiveness of this surgical approach. PATIENTS AND METHODS: We retrospectively reviewed our 31 laparoscopic nephrectomies performed from November 2002 to November 2005. In all the procedures, both the renal artery and the renal vein were secured using only NPL clips. For each patient, the operative time, estimated blood loss, early and late complications, and length of hospital stay were analyzed. Further, we performed a MEDLINE search for laparoscopic nephrectomies in which both the renal artery and the vein were secured using only Hem-o-lok clips. RESULTS: No renal vessel injuries, cases of clip dislodgement or slippage, or bleeding were recorded. Worthy of note, we achieved a meaningful reduction in the cost per procedure. To the best of our knowledge, renal-pedicle control exclusively with Hem-o-lok clips during purely laparoscopic nephrectomy has not been yet published. CONCLUSIONS: Any device or technique for vascular control is prone to malfunction in either open or laparoscopic surgery. The described approach is safe, reliable, rapid, and inexpensive. PMID- 17867954 TI - Splenic injury: rare complication of percutaneous nephrolithotomy: report of two cases with review of literature. AB - BACKGROUND: Splenic injury is an uncommon complication of percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: We report herewith two cases of splenic injury that occurred during puncture of the 10th intercostal-space for PCNL. RESULTS AND CONCLUSIONS: One of these patients presented with hypotension on day 5 after discharge from the hospital. Both patients needed emergency laparotomy, and one of them required splenectomy for management of the injury. We reviewed the literature to determine the risk factors and management of splenic injury during PCNL. PMID- 17867955 TI - Case report: delayed hemorrhage from an accessory internal pudendal artery pseudoaneurysm after robotic radical prostatectomy: successful management with ct angiography and embolization. AB - We present the first report of a pseudoaneurysm of an accessory internal pudendal artery after transperitoneal robotic radical prostatectomy. The vesicourethral anastomosis was performed using two continuous 3-0 Monocryl sutures tied at the six o'clock position. As the anastomotic suture was placed at 11 o'clock, lateral to the dorsal venous complex, there was a small amount of pulsatile bleeding that ceased when the suture was completed and tied. The lesion presented as hematuria beginning on the fourth day. On the 14(th) day, the pseudoaneurysm was diagnosed by CT angiography and treated by embolization with eight 3-mm/30-mm micro coils after superselective catheterization. There were no complications or further hematuria. PMID- 17867956 TI - Comparison of laparoscopic and abdominal sacrocolpopexy for the treatment of vaginal vault prolapse. AB - BACKGROUND AND PURPOSE: Laparoscopic sacrocolpopexy (LSCP) offers a minimally invasive treatment for vaginal vault prolapse. We describe the surgical technique and offer insight into the learning curve. In addition, we performed a case series review comparing the laparoscopic procedure with its open surgical counterpart with respect to various demographic and perioperative parameters. PATIENTS AND METHODS: The Institutional Review Board-approved continence database at our institution was queried to identify all patients undergoing sacrocolpopexy between August 1999 and October 2004. The LSCP was performed in 25 patients, and open abdominal sacrocolpopexy (ASCP) was performed in 22 patients. Data were analyzed using Student's t-test and the Fisher exact test. RESULTS: No significant difference was observed in the demographic characteristics of the patients undergoing the two approaches. The mean estimated blood loss (P = 0.0002) and mean length of hospitalization (P < 0.0001) were significantly less for LSCP, whereas the operative time was significantly longer (219.9 minutes v 185.2 minutes; P = 0.045). The success rate for LSCP at 5.9 months was 100%; the ASCP success rate at 11.0 months was 95%. CONCLUSIONS: Laparoscopic sacrocolpopexy led to shorter hospitalization, better hemostasis, and less pain than the open procedure. Early follow-up suggests that LSCP is as effective as ASCP for the treatment of vaginal vault prolapse. PMID- 17867957 TI - Experimental evaluation of suture support in bladder-neck suspension for the treatment of female stress urinary incontinence. AB - BACKGROUND AND PURPOSE: Bladder-neck suspension has been used widely for the management of female stress incontinence. Despite high early success rates, the long-term results are poor. This in-vitro model was designed to simulate the tear forces affecting the sutures under standardized laboratory conditions. MATERIALS AND METHODS: First, we determined the ultimate strength of various tissues (porcine vagina [PV], human vagina [HV], porcine colon, and chicken skin) in resisting standardized traction force and expansion. Subsequently, different types of suture fixation (U stitch, Z stitch, patch suspension) and button techniques (titanium 2 mm and buttons with various diameters) on PV were exposed to standardized stress impulses generated by the horizontal movement of a metal sledge and the traction force of a 0.5-kg weight pulling on the suture. Amplitude, frequency of the sine movement, traction force on the suture, and tissue thickness were modified; and the tear-out time of the fixation (suture, button) was measured. RESULTS: The PV and HV revealed similar ultimate strengths (49.04 N and 32.08 N, respectively, for traction force; 58.25% and 58.20%, respectively, for expansion). Increasing the frequency (110-160/min), amplitude (8-24 cm), or traction force (0.3-1.2 N) shortened the tear-out time. Tissue thickness had a nearly linear correlation with the tear-out time. The conventional suture technique was almost equal to the smaller buttons (8 and 12 mm) in tear-out resistance, but the 20-mm button was superior (2.6-fold increase in tear-out time). Further improvement of the button technique could be achieved by use of round silicone-coated buttons with medium hardness (shore 40). CONCLUSION: A button-like support is promising, being superior to conventional suturing. Compared with tension-free vaginal tape, it provides the advantage that paraurethral suspension prevents erosion of a foreign body through the urethra. Further technical improvements may include adjustment devices for postoperative fine-tuning of the bladder-neck suspension. PMID- 17867958 TI - Efficacy of laser-activated gold nanoshells in ablating prostate cancer cells in vitro. AB - BACKGROUND AND PURPOSE: Nanoshells (NS) are nanoparticles consisting of a dielectric silica core covered by a thin gold shell. Nanoshells can be designed to absorb near-infrared (NIR) light strongly to generate heat and provide optically guided hyperthermic ablation. Laser-activated gold nanoshells (LAGN) may offer a minimally invasive targeted ablative treatment for prostate cancer. We studied the in-vitro effectiveness of LAGN ablation on human prostate cancer cells. MATERIALS AND METHODS: Two human prostate cancer (PCa) cell lines, PC-3 and C4-2, were grown to 80% confluency in T medium with 5% fetal bovine serum. In order to determine a threshold concentration of gold nanoshells (GNS) needed to achieve full cellular ablation, dose titration was performed. In subsequent experiments, GNS were added to PCa cells in phosphate-buffered saline at concentrations above the predetermined threshold. The cells were then exposed to NIR light (810 nm, 88 W/cm2) for 5 minutes and stained immediately for viability using the Calcein AM assay. For determining long-term cell survival, the crystal violet assay was employed. RESULTS: The GNS could be evenly distributed across the culture plates. A ratio of 5000 GNS per PCa cell was critical for achieving cell kill. Cells treated with GNS + NIR demonstrated a laser-specific zone of cell death. The crystal violet viability assay confirmed consistent cell death rather than induction of cell dormancy. Cells treated with GNS alone or with NIR light alone demonstrated no toxicity. CONCLUSION: Laser-activated gold nanoshells can ablate human PCa cells in vitro. This nanoparticle technology is an attractive therapeutic agent for selective tumor ablation. PMID- 17867963 TI - Out of Rockville and Laurel. FDA-CVM initiatives span individualized medicine to aquaculture research. PMID- 17867964 TI - More on the legal status of animals. PMID- 17867965 TI - A proposed novel food animal health care delivery system. PMID- 17867966 TI - What is your diagnosis? Cystic meningioma. PMID- 17867967 TI - What is your diagnosis? Retrobulbar neoplasia. PMID- 17867968 TI - Theriogenology question of the month. The infected bitch should be euthanized. The other dogs in the kennel should be quarantined. PMID- 17867969 TI - Income of US veterinarians, 2005. PMID- 17867970 TI - Aquatic zoonoses associated with food, bait, ornamental, and tropical fish. PMID- 17867972 TI - Evaluation of a circumferential femoral head osteophyte as an early indicator of osteoarthritis characteristic of canine hip dysplasia in dogs. AB - OBJECTIVE: To determine the relationship between a circumferential femoral head osteophyte (CFHO) and osteoarthritis characteristic of canine hip dysplasia, and to ascertain whether CFHO, like osteoarthritis, varies between diet-restricted and control-fed dogs. DESIGN: Longitudinal cohort study. ANIMALS: 48 Labrador Retrievers. PROCEDURES: Dogs were paired by size, sex, and litter and assigned to 1 of 2 equal groups at 2 months of age. The control-fed group was fed ad libitum, and the diet-restricted group was fed 25% less on a pairwise basis of the same diet for life. The dogs' hip joints were radiographed yearly for life. Each radiograph was evaluated for radiographic signs of osteoarthritis characteristic of hip dysplasia and for the presence and severity of a CFHO. RESULTS: 41 of the 48 (85.4%) dogs had a CFHO, which was detected at a median age of 5.4 years, and 33 of those 41 (80.5%) developed radiographic evidence of osteoarthritis. Nineteen (79.2%) dogs in the diet-restricted group and 22 (91.7%) in the control fed group had a CFHO at a median age of 9 and 3 years, respectively. Of the dogs with a CFHO, 12 (63.2%) in the diet-restricted group and 20 (90.0%) in the control-fed group developed radiographic evidence of osteoarthritis characteristic of hip dysplasia at a median age of 11 and 6.5 years, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated a relationship between the CFHO and subsequent development of radiographic signs of osteoarthritis. If a CFHO is present in Labrador Retrievers, it might be considered an early indicator of osteoarthritis. PMID- 17867973 TI - Frequency of urinary tract infection in catheterized dogs and comparison of bacterial culture and susceptibility testing results for catheterized and noncatheterized dogs with urinary tract infections. AB - OBJECTIVE: To determine frequency of urinary tract infections (UTIs) in catheterized dogs that had intervertebral disk disease (IVDD) or disease other than IVDD and compare bacterial culture and susceptibility testing results for catheterized and noncatheterized dogs with UTIs. DESIGN: Retrospective cohort study. ANIMALS: 147 catheterized dogs (105 with IVDD and 42 with other diseases) and 99 noncatheterized dogs with UTIs. PROCEDURES: Medical records were reviewed for signalment, history, clinical problem, duration of urinary tract catheterization, administration of drugs, and urine bacterial culture and susceptibility testing results. RESULTS: Forty-two percent (44/105) of dogs with IVDD and 55% (23/42) of dogs with other diseases had UTIs; this difference was not significant. For catheterized dogs, the odds of UTI were increased by 20% for each year increase in age, 27% for each day increase in duration of catheterization, and 454% with antimicrobial administration. Escherichia coli and Proteus spp were more frequently isolated from noncatheterized dogs, whereas Enterobacter spp and Staphylococcus spp were more frequently isolated from catheterized dogs. There was no significant difference in frequency of 1, 2, or 3 isolates between groups. Proportions of antimicrobials to which the most frequently isolated bacteria were resistant were not significantly different between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that urinary tract catheterization is a reasonable alternative for management of dogs with urinary bladder dysfunction, but that duration of catheterization should be minimized and indiscriminate antimicrobial administration to dogs with indwelling urinary catheters should be avoided. PMID- 17867974 TI - Pharmacokinetics of an extended-release theophylline product in cats. AB - OBJECTIVE: To evaluate the pharmacokinetics of a brand of extended-release theophylline tablets and capsules in healthy cats. DESIGN: Randomized 3-way crossover study. ANIMALS: 6 healthy cats. PROCEDURES: A single dose of aminophylline (10 mg/kg [4.5 mg/lb], IV), a 100-mg extended-release theophylline tablet, or a 125-mg extended-release theophylline capsule was administered to all cats. Plasma samples were collected via preplaced central catheters throughout a 36-hour period. Plasma samples were frozen until analyzed by use of a fluorescence polarization monoclonal immunoassay. RESULTS: All cats tolerated drug administration and plasma collection with no adverse effects. Peak concentrations were reached for both orally administered products between 8 and 12 hours after administration. Bioavailability was excellent. Plasma concentrations were within the human therapeutic concentration of 5 to 20 microg/mL. CONCLUSIONS AND CLINICAL RELEVANCE: Daily administration of the brand of theophylline tablets and capsules used in this study at 15 mg/kg (6.8 mg/lb) and 19 mg/kg (8.6 mg/lb), respectively, maintained plasma concentrations within the desired therapeutic range in healthy cats. PMID- 17867975 TI - Blanket and flank sucking in Doberman Pinschers. AB - OBJECTIVE: To evaluate blanket and flank sucking and any association with pica in Doberman Pinschers. DESIGN: Survey and case-control study. ANIMALS: 153 Doberman Pinschers (77 dogs with blanket or flank sucking and 76 unaffected dogs). PROCEDURES: Owners of Doberman Pinschers with blanket sucking, flank sucking, or both were surveyed regarding the age of onset, triggers, frequency, duration, interruptability, and associated medical and behavioral consequences. A putative association of blanket sucking and flank sucking with pica was examined by comparison of affected dogs with unaffected dogs. RESULTS: Apart from the difference in the object of oral activity between blanket and flank suckers, age of onset was the only variable that differed between dogs with the 2 conditions. Dogs with blanket or flank sucking had a higher prevalence of pica than the unaffected population. CONCLUSIONS AND CLINICAL RELEVANCE: Blanket and flank sucking are apparently related conditions that can occur with sufficient intensity to cause medical sequelae. These nonnutritive suckling behaviors share similarities with other canine compulsive disorders and are associated with pica. Veterinarians should advise owners that flank and blanket sucking are abnormal, potentially harmful behaviors in dogs. Treatment should be considered for severely affected dogs or when flank or blanket sucking is associated with medical problems. PMID- 17867976 TI - Evaluation of electroacupuncture treatment for thoracolumbar intervertebral disk disease in dogs. AB - OBJECTIVE: To evaluate use of electroacupuncture combined with standard Western medical treatment versus Western medical treatment alone for treatment of thoracolumbar intervertebral disk disease in dogs. DESIGN: Prospective controlled study. ANIMALS: 50 dogs with signs of thoracolumbar intervertebral disk disease. PROCEDURES: Dogs were randomly allocated to 1 of 2 treatment groups and classified as having grade 1 to 5 neurologic dysfunction. Dogs in group 1 received electroacupuncture stimulation combined with standard Western medical treatment; those in group 2 received only standard Western medical treatment. A numeric score for neurologic function was evaluated at 4 time points to evaluate effects of treatments. RESULTS: Time (mean +/- SD) to recover ambulation in dogs with grade 3 and 4 dysfunction in group 1 (10.10 +/- 6.49 days) was significantly lower than in group 2 (20.83 +/- 11.99 days). Success (able to walk without assistance) rate for dogs with grade 3 and 4 dysfunction in group 1 (10/10 dogs) was significantly higher than that of similarly affected dogs in group 2 (6/9 dogs). Dogs without deep pain perception (grade 5 dysfunction) had a success (recovery of pain sensation) rate of 3 of 6 and 1 of 8 in groups 1 and 2, respectively, but the difference was not significant. Overall success rate (all dysfunction grades) for group 1 (23/26; 88.5%) was significantly higher than for group 2 (14/24; 58.3%). CONCLUSIONS AND CLINICAL RELEVANCE: Electroacupuncture combined with standard Western medical treatment was effective and resulted in shorter time to recover ambulation and deep pain perception than did use of Western treatment alone in dogs with signs of thoracolumbar intervertebral disk disease. PMID- 17867977 TI - Spontaneous external biliary fistula in a dog. AB - CASE DESCRIPTION: A 10-year-old sexually intact female dog was examined because of a static, well-circumscribed subcutaneous mass and associated fistulous draining tract located along the right ventrolateral aspect of the thoracic body wall of 15 months' duration. CLINICAL FINDINGS: Results of computed tomography and fistulography confirmed the presence of the fistulous tract. Computed tomography also revealed a focal, hypodense region in the right ventral portion of the liver that was adjacent to but not clearly associated with the fistulous tract. TREATMENT AND OUTCOME: Surgical exploration of the tract revealed that it passed into the right hemithorax to the diaphragm; entered the right medial lobe of the liver; and terminated in a well-encapsulated, cystic liver lesion. The right medial liver lobe and all affected tissues were removed. Histologically, the liver lesion consisted of a fibrotic, dilated bile duct. The dilated bile duct and fistula were lined with biliary epithelium. On the basis of these findings, a diagnosis of spontaneous external biliary fistula was made. Five months after surgery, the dog was clinically normal. CLINICAL RELEVANCE: To the authors' knowledge, spontaneous external biliary fistula in a dog has not been reported in the veterinary medical literature. Despite the rarity of this condition, it should be considered in a dog with similar clinical findings. Clinical findings and results of appropriate diagnostic imaging procedures may provide valuable information in making this diagnosis and in planning surgical treatment. PMID- 17867978 TI - Computed tomographic appearance of masticatory myositis in dogs: 7 cases (1999 2006). AB - OBJECTIVE: To document computed tomography (CT) features in dogs with masticatory myositis. DESIGN: Retrospective case series. ANIMALS: 7 dogs with an immunologic diagnosis of masticatory myositis and an absence of clinical abnormalities of any skeletal muscles other than the masticatory muscles. PROCEDURES: History; clinical, hematologic, biochemical, immunologic, cytologic, and histologic findings; and pre- and postcontrast CT imaging features of masticatory muscles and head and neck lymph nodes were extracted from medical records. RESULTS: On CT images, changes in size (atrophy or swelling) were common for all masticatory muscles except the digastricus muscles, which were involved only in 1 dog. Pre contrast attenuation changes, most often hypoattenuation with varied distribution patterns, were seen in masticatory muscles of 4 dogs. Contrast enhancement with a predominantly inhomogeneous distribution pattern was seen in the temporalis, masseter, and pterygoid muscles of all dogs. Head and neck lymph nodes were enlarged in all but 1 dog and had contrast enhancement with predominantly central or homogeneous distribution patterns. Muscle biopsy was performed in 6 dogs, with biopsy specimens obtained from areas that had the most obvious contrast enhancement on CT images. For all 6 dogs, biopsy specimens had histologic features indicative of masticatory myositis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that CT may be a useful adjunct in the diagnosis of masticatory myositis in dogs, including selection of sites for diagnostic muscle biopsy. PMID- 17867981 TI - Interpretation of laboratory results: the reference intervals, a necessary evil? PMID- 17867979 TI - Comparison of the diagnosis and management of unilaterally castrated and cryptorchid horses at a referral hospital: 60 cases (2002-2006). AB - OBJECTIVE: To determine the incidence of unilaterally castrated horses among horses admitted to the hospital for castration and to compare horses that underwent previous unilateral castration with horses that had cryptorchism. DESIGN: Retrospective case series. ANIMALS: 16 unilaterally castrated horses and 44 cryptorchid horses. PROCEDURES: Medical records of horses that were admitted to the veterinary medical teaching hospital for castration, including cryptorchid and unilaterally castrated horses, between January 2002 and December 2006 were reviewed. Medical records of unilaterally castrated horses and cryptorchid horses were examined for age, breed, history, diagnostic procedures, surgical technique of cryptorchidectomy, location of the retained testicle, and cost of surgery. RESULTS: Of 160 horses admitted for castration, 16 (10%) had undergone previous unilateral castration and 44 (27.5%) had cryptorchidism. Unilaterally castrated horses were significantly older than cryptorchid horses. No significant difference was found in left versus right distribution of testicles. No significant difference was found in abdominal versus inguinal distribution of left-sided testicles. Unilaterally castrated horses had a significantly lower proportion of right inguinal testicles, compared with cryptorchid horses. The cost of diagnosis and management of unilaterally castrated horses was significantly greater than in cryptorchid horses. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the distribution of retained testicles is significantly different in unilaterally castrated horses, compared with cryptorchid horses, which may affect the selection of diagnostic and surgical approaches to unilaterally castrated horses. PMID- 17867982 TI - Implementation of haemoglobin A1c results traceable to the IFCC reference system: the way forward. PMID- 17867983 TI - Exhaled breath condensate: a new method for lung disease diagnosis. AB - Analysis of exhaled breath composition in lung disease patients can indirectly point to biochemical changes that occur in the fluid lining airway surfaces. The parameters of redox and acid-base changes, and of inflammatory changes relevant in the pathogenesis of most pulmonary diseases are currently most widely determined in exhaled breath condensate. The collection of exhaled breath condensate is a safe, non-invasive, easy and simple diagnostic procedure that is suitable for longitudinal studies and applicable in patients of all age groups, irrespective of the disease severity. In spite of many scientific studies involving lung disease patients, methodology for exhaled breath condensate collection and analysis has not yet been realized for daily utilization. Additional studies of the exact origin of condensate constituents and standardization of the overall analytical process, including collection, storage, analysis and result interpretation, are needed. Irrespective of these limitations, further investigation of this sample type is fully justified by the fact that classical specimens used in the management of pulmonary disease are either obtained by invasive procedures (e.g., induced sputum, biopsy, bronchoalveolar lavage) or cannot provide appropriate information (e.g., urine, serum). Analysis of exhaled breath condensate in the future might contribute significantly to our understanding of the physiological and pathophysiological processes in lungs, to early detection, diagnosis and follow up of disease progression, and to evaluation of therapeutic response. PMID- 17867984 TI - Association of interleukin-1 genetic polymorphisms with the risk of rheumatoid arthritis in Chinese population. AB - BACKGROUND: Previous studies suggest that a variable number of tandem repeats polymorphism in the second intron of the interleukin-1 receptor antagonist gene and two single nucleotide polymorphisms at positions -511 and +3954 of the interleukin-1beta (IL-1B) gene are associated with an increased risk of autoimmune diseases. In the present study, we evaluated associations between these genetic factors and an increased risk of rheumatoid arthritis (RA) in a population from Northwest China. METHODS: A total of 240 patients with RA and 227 healthy controls from Northwest China were investigated using PCR and PCR restriction fragment length polymorphism. Genotype and allele distributions and haplotype construction were analyzed. RESULTS: The genotype and allele distributions of IL-1B +3954 and IL-1RN polymorphisms were significantly different in RA patients compared to controls (p<0.001 and p<0.001; p=0.028, p=0.023, respectively). Significant differences were also observed between the RA and control groups for the haplotypes IL-1B -511C/+3954C/IL-1RN *1, IL-1B 511C/+3954T/IL-1RN *1 and IL-1B -511T/+3954T/IL-1RN *1 [p=0.017, odds ratio (OR) 0.721, 95% confidence interval (CI) 0.551-0.944; p=0.030, OR 2.111, 95% CI 1.060 4.204; and p=0.029, OR 2.909, 95% CI 1.066-7.902, respectively]. CONCLUSIONS: These findings suggest that IL-1B +3954 and IL-1RN genetic polymorphisms are associated with a significantly increased risk of RA in this Chinese population. PMID- 17867985 TI - Highest accuracy of combined consensus clinical criteria and SNRPN gene molecular markers in diagnosis of Prader-Willi syndrome in Thai patients. AB - BACKGROUND: Prader-Willi Syndrome (PWS) is a complex human genetic disease arising from a loss of paternal allele expression of imprinting genes on chromosome 15q11-q13. Normally the CpG islands at this site are heavily methylated in the maternal allele, but unmethylated in the paternal allele and therefore activated in gene expression. only the methylated allele should present in pws patients when methylation-specific pcr (msp) is analyzed. METHODS: This paper reports an analysis of PWS in Thai patients using consensus diagnostic criteria based on a combination of clinical data, basic G-banding and fluorescence in situ hybridization (FISH) cytogenetics, PCR-based methylation assay, and bisulfite sequencing of the CpG islands of SNRPN to confirm 15q deletion or the methylation pattern of the SNRPN promoter and exon 1. Lack of complete clinical reports or inadequacy of the minimum laboratory support required had made it difficult to diagnose PWS, Angelman syndrome and other microdeletion disorders. RESULTS: Accuracy of 100% was obtained for diagnosis of the PWS study patients using the minimum requirements necessary. A total of 20 patients were diagnosed as PWS based on clinical criteria and the scoring tool for PWS, and the same approach was applied to four separate patients with some unmatched criteria but phenotypic similarity to PWS. Findings showed that 70% of those clinically diagnosed as PWS patients (14/20) had a deletion at 15q11-q13 according to FISH, while all 20 patients showed MSP positive of SNRPN gene. Six cases (30%) without a paternal deletion were confirmed to have maternal uniparental disomy (mUPD) of PWS by MSP and methylation sequencing approaches. Noteworthy, two of the six cases with mUPD were 3.5 year-old twins. None of the five cases with scores lower than the reported consensus criteria showed positive G-band, FISH or MSP results. CONCLUSIONS: We demonstrate here the high power of combining clinical findings, FISH and MSP in definitive diagnosis of PWS and in distinguishing between the two major different types of molecular mechanisms. No false positives or false negatives were observed in our analysis. PMID- 17867986 TI - Use of maternal plasma for non-invasive prenatal diagnosis of fetal ABO genotypes. AB - BACKGROUND: Measurement of free fetal DNA in maternal plasma opened a door for non-invasive prenatal diagnosis. Prenatal diagnosis of fetal ABO genotypes can provide a basis for the prevention and therapy of maternal-fetal incompatibility. We identified fetal ABO genotypes using fetal DNA in plasma from pregnant women with blood group O. The aim of the study was to investigate the accuracy and feasibility of this method. METHODS: A total of 105 blood group O women in middle or late pregnancy were enrolled. Fetal DNA in maternal plasma and genomic DNA in umbilical vein blood from newborns were extracted using a QIAamp DNA Blood Kit. DNA was amplified to identify ABO genotypes by PCR with sequence-specific primers (PCR-SSP). The genotype results were evaluated using serologic tests for ABO phenotyping. RESULTS: Using DNA from umbilical vein blood, ABO genotypes of 105 newborns were successfully identified by PCR-SSP. Using fetal DNA from maternal plasma, 88.6% (93/105) fetal ABO genotypes was correct; 12 false results were from 66 pregnant women with fetuses of type non-O. The accuracy in middle pregnancy was lower than that in late pregnancy, although the difference was not significant (0.05or=50 years) and was significant for AST (females only), gamma-GT and lipase, not significant for amylase and inconsistent for AP, LDH and ALT. For gamma-GT, further stratification for age in decades was necessary for males. Creatine kinase MB (CK-MB) values were not stratified owing to the low number of data available. CONCLUSIONS: Retrospective RLs derived from intra-laboratory data pools for the catalytic activity concentration of enzymes using a modified procedure plausibly agreed with published consensus values. However, most RLs varied significantly among laboratories, thus supporting the "old" plea for intra-laboratory RLs. PMID- 17867995 TI - Monitoring glycaemic control: is there evidence for appropriate use of routine measurement of glycated haemoglobin? AB - BACKGROUND: Regardless of the available recommendations to perform glycated haemoglobin testing at a 2- to 3-month frequency, there is increasing evidence of an inappropriate laboratory use of this test in clinical practice. METHODS: Data from our Laboratory Information System were analysed for glycated haemoglobin test orders over a 3-year period using Microsoft Excel to calculate the order intervals and the test frequency for each patient. To assess the appropriateness of repeat testing, only data for patients who had at least two separate glycated haemoglobin test results were included in the analysis. Inappropriate test orders were defined as any order for a given patient taking place within a 29- or 89-day period following the previous order. RESULTS: The results of our investigation demonstrate that inappropriate laboratory utilisation of this test is commonplace (26% of total repeat orders within 90 days), especially for inpatients (63.7% of inpatient repeat orders in less than 90 days). When stratifying glycated haemoglobin test results according to the >7% threshold, the frequency of inappropriate laboratory use (>90 days) was surprisingly greater among inpatients with a previous value of <7% than among those with a previous value of >7% (57.6% vs. 42.4%). The frequency of inappropriate glycated haemoglobin repeat test orders was lower among outpatients with a previous value of <7% than in outpatients with a previous value of >7% (64.8% vs. 35.2%). CONCLUSIONS: We conclude that more accurate application of the current recommendations would be advisable to decrease unnecessary testing and prevent avoidable health expenditure. PMID- 17867996 TI - Hook effect in calcitonin immunoradiometric assay. PMID- 17867997 TI - Rapid genotyping of the Ser447Stop variant of the lipoprotein lipase gene using real-time fluorescent PCR. PMID- 17867998 TI - Global standardization of glycated hemoglobin measurement: the position of the IFCC Working Group. AB - The measurement of glycated hemoglobin is central in the monitoring of glycemic control in patients with diabetes. There are at least 30 different laboratory assays commercially available to measure the proportion of HbA1c in blood. In 1995 the IFCC established a Working Group (IFCC WG-HbA1c) to achieve international standardization of HbA1c measurement. The main achievements can be summarized as follows: a) a reference measurement procedure has been established with purified primary calibrators; b) a network of reference laboratories has been developed worldwide; and c) work has begun on implementation of traceability to the IFCC reference system. The IFCC WG-HbA1c recognizes the recommendation of the IFCC-IUPAC Committee on Nomenclature, Properties and Units that the analyte measured by the IFCC reference measurement procedure has been defined as betaN1 deoxyfructosyl-hemoglobin and that the recommended measurement units are mmol/mol. The IFCC WG-HbA1c recommends maintaining the use of the name HbA1c in clinical practice. PMID- 17867999 TI - Recommendation for term and measurement unit for "HbA1c". PMID- 17868000 TI - IFCC position paper: report of the IFCC taskforce on ethics: introduction and framework. AB - Laboratory Medicine organizations and their professional members have a goal and responsibility to benefit the health and wellbeing of the patients and communities they serve. Newer genetics and biochemical techniques raise significant issues of community concern, impacting on privacy, informed consent, access to and retention of samples and information. Balance may be required to ensure protection of individual rights against potential benefits to the broader community. While many national organizations may already have appropriate policies addressing various ethics issues, there is a need for an international framework to assist those nations that have not yet developed such policies, as well as to enable alignment of existing national policies. We have proposed a generic ethics framework, incorporating a hierarchy of four fundamental guiding principles: autonomy, justice, non-maleficence and beneficence. Proposals or issues requiring policy development can be considered and tested against this hierarchy, resulting in the development of policy and positions consistent with the above framework, acceptable to all participating stakeholders. PMID- 17868003 TI - Chronic (transformed) migraine and medication overuse: to withdraw or not? PMID- 17868004 TI - Migraine and suicide. PMID- 17868006 TI - Zonisamide for the treatment of Parkinson's disease. AB - Zonisamide is an antiepileptic drug widely used to treat seizures worldwide. In addition to epilepsy, zonisamide may have beneficial efficacy in various neurological or psychiatric diseases. This article reviews the structure, mechanism of action, pharmacokinetics and possible antiparkinsonian action of zonisamide. A multicentered, randomized, double-blind, placebo-controlled study conducted in Japan provided data suggesting that zonisamide, as an add-on treatment, has efficacy in treating motor symptoms in patients with Parkinson's disease (PD). Zonisamide may be effective in reducing the duration of 'off' time in patients with PD treated with L-DOPA. The therapeutic doses of zonisamide for the treatment of PD are 50-100 mg/day, considerably lower than those for the treatment of epilepsy (200-400 mg/day). It is expected that zonisamide will be safe and tolerated in patients with PD, as it has been used as an antiepileptic for more than 15 years; however, further studies are required to evaluate its safety and tolerability in the treatment of PD. The pharmacological mechanisms of the beneficial actions of zonisamide in PD remain unclear. Various hypotheses have been proposed, but the supporting data are not yet sufficient to draw any conclusions. Further basic research is required to advance our understanding of the antiparkinsonian mechanism of zonisamide. PMID- 17868007 TI - The PRoFESS trial: future impact on secondary stroke prevention. AB - Patients with transient ischemic attack and ischemic stroke have a high risk of recurrent stroke and death. While aspirin is accepted as standard therapy in these patients, recent trials demonstrate that a combination of aspirin and extended-release dipyridamole or clopidogrel is superior to aspirin monotherapy. Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers may also reduce recurrent stroke. The ongoing Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial is designed to evaluate whether extended-release dipyridamole plus aspirin compared with clopidogrel, and whether telmisartan in addition to usual care, in individuals after a stroke, will reduce the risk of further strokes. PRoFESS is a multicenter, randomized, double-blind trial involving 695 sites from 35 countries or regions. The primary outcome for the trial is recurrent stroke, using a time to-event analysis. Safety is evaluated by assessing the risk of major hemorrhagic and other serious adverse events. With over 20,000 patients randomized, and utilizing a 2 x 2 factorial design, PRoFESS is the largest stroke trial to investigate the prevention of recurrent stroke. PMID- 17868008 TI - 49th annual scientific meeting of the American Headache Society 2007. PMID- 17868009 TI - Associations between migraine and cardiovascular disease. AB - Migraine is a common chronic, intermittent headache disorder that in some patients is accompanied by neurological symptoms, particularly visual symptoms, known as migraine aura. Several population-based studies have linked migraine, and particularly migraine with aura, with increased risk of ischemic stroke. Recent prospective data suggest an association between migraine with aura and any ischemic vascular events, including coronary heart disease. The precise biological mechanism by which migraine with aura may increase the risk of vascular events is currently unknown and likely complex. Potential mechanisms involve shared risk factors, inter-relationships between migraine and vascular pathologies, migraine treatments, as well as genetic components. This review aims to summarize the epidemiologic evidence linking migraine with ischemic vascular events, discuss potential mechanisms and to outline potential consequences. PMID- 17868010 TI - Menstrual migraine: clinical and therapeutical aspects. AB - Estrogens fluctuations, particularly their premenstrual fall, are currently regarded as the main triggers of menstrual migraine (MM). MM presents in two clinical forms: pure MM, where attacks are confined to the perimenstrual period (PMP), and menstrually related migraine, where attacks always occur during, but are not confined to, the PMP. MM episodes are usually longer, more intense, more disabling and more refractory than nonmenstrual attacks. Acute management of MM should initially be abortive and primarily sought with triptans. If this fails, short-term perimenstrual prophylaxis with NSAIDs, coxibs, triptans or ergotamine derivatives can be considered. Hormone manipulations, mainly application of percutaneous estradiol gel in PMP or administration of oral contraceptives in extended cycles, constitute an alternative approach for nonresponders. PMID- 17868011 TI - Role of acupuncture in the treatment of migraine. AB - Since the last Cochrane review of acupuncture and headache in 2001, which found methodological and/or reporting shortcomings in the majority of the studies, several large, randomized trials on the effectiveness of acupuncture as a treatment for headache have been published. Following a brief overview of the pathophysiology of migraine and possible action mechanisms of acupuncture, we look at current studies on acupuncture and migraine and discuss the results. From these results and our own studies on acupuncture and migraine, we conclude that a 6-week course of acupuncture is not inferior to a 6-month prophylactic drug treatment, but that specific Chinese point selection, point stimulation and needling depth are not as important as had been thought. The review suggests that acupuncture should be integrated into existing migraine therapy protocols. PMID- 17868012 TI - Clinical spectrum of thunderclap headache. AB - Headaches of the thunderclap variety become severe in intensity within seconds to a minute of onset. Patients with thunderclap headache are to be evaluated in an emergent fashion as many of the underlying causes are associated with significant morbidity and mortality. Although subarachnoid hemorrhage is usually the initial consideration, a multitude of other etiologies have been identified and are discussed herein. In accordance with the increased utilization of cerebral imaging, availability of noninvasive techniques to image the cerebral vasculature and interest in identifying causes of thunderclap headaches, the list of potential causes is growing rapidly. Included in this growth are the reversible cerebral vasoconstriction syndromes, terminology recently introduced to unify several disorders all presenting with thunderclap headache and similar diagnostic findings including reversible vasoconstriction of the intracranial arteries. PMID- 17868013 TI - Management of medication-overuse headache. AB - Medication-overuse headache (MOH) has developed into the third most common type of headache after tension-type headache and migraine. The prevalence reaches approximately 1% of the world's population and shows an increasing trend. Many important studies on MOH have been published in the last year, some of which investigated the pathophysiology of headache chronicity, with others focusing on the evaluation of risk factors. The International Headache Society revised its classification criteria on MOH. Several large population-based longitudinal studies clearly demonstrated that overuse of any kind of acute headache medication is the main risk factor leading to the development of chronic headache. Management of MOH remains difficult; the only effective treatment concept is consequent withdrawal therapy. PMID- 17868014 TI - Symptomatic treatment of multiple sclerosis using cannabinoids: recent advances. AB - Recent years have seen a dramatic increase in the number of clinical trials investigating the potential efficacy of medicinal cannabinoids for the symptomatic treatment of chronic pain and spasticity in multiple sclerosis (MS). A number of different cannabinoids have been used, including: delta9 tetrahydrocannabinol (THC) itself; the synthetic delta9-THC, dronabinol; a 1:1 ratio of delta9-THC:cannabidiol (Sativex); and the synthetic delta9-THC metabolites CT-3 and nabilone. Other Cannabis extracts have also been tested. While 2-3 years ago there was little consensus in the literature, now the majority of studies are beginning to suggest that cannabinoids are useful in the treatment of MS in at least a subset of individuals. Their adverse side-effect profile has generally been mild compared with other drugs used for pain and spasticity; nonetheless, there is still concern about potential long-term side effects, particularly psychiatric side effects and effects on fetal development. PMID- 17868015 TI - Pharmacological treatment of pain in multiple sclerosis. AB - Pain is a common symptom in multiple sclerosis (MS) and was recently estimated to be experienced by up to 75% of patients. Nociceptive and neuropathic pain in MS may be present concurrently and at different stages of the disease and may be associated with other symptoms. Evidence for treating pain in MS is limited. Many clinical features of pain are often unrecognized by clinicians and are difficult for patients to describe. Treatment is often based on anecdotal reports and clinical experience. We present a review of treatment options for pain in MS that should serve to update current knowledge, highlight shortcomings in clinical research and provide indications towards achieving evidence-based treatment of pain in MS. PMID- 17868016 TI - Recent advances in genetic analysis of multiple sclerosis: genetic associations and therapeutic implications. AB - Epidemiological studies have confirmed that genetic factors are a key component in the pathogenesis of multiple sclerosis (MS) and that those determining MS susceptibility have been extensively studied. Many papers have been published regarding the heritable differences useful in genetic studies; these include variations in DNA, such as single-nucleotide polymorphisms, microsatellites and insertion/deletion polymorphisms. However, to date, among other regions, HLA is the only region confirmed to possess genes that determine MS susceptibility. In this article, we review the progress during the last 5 years in the studies on the susceptibility genes and the pharmacogenetics of MS. Newer techniques and methods of analysis will hopefully result in better screening of individuals who are at highest risk and novel treatments. PMID- 17868017 TI - Use of stem cells for the treatment of multiple sclerosis. AB - The reported evidence of neurodegeneration in multiple sclerosis (MS) may explain the lack of efficacy of the currently used immunomodulating modalities and the irreversible axonal damage, which results in accumulating disability. To date, efforts for neuroprotective treatments have not been successful in clinical studies in other CNS diseases. Therefore, for MS, the use of stem cells may provide a logical solution, since these cells can migrate locally into the areas of white-matter lesions (plaques) and have the potential to support local neurogenesis and rebuilding of the affected myelin. This is achieved both by support of the resident CNS stem cell repertoire and by differentiation of the transplanted cells into neurons and myelin-producing cells (oligodendrocytes). Stem cells were also shown to possess immunomodulating properties, inducing systemic and local suppression of the myelin-targeting autoimmune lymphocytes. Several types of stem cells (embryonic and adult) have been described and extensively studied in animal models of CNS diseases and the various models of MS (experimental autoimmune encephalomyelitis [EAE]). In this review, we summarize the experience with the use of different types of stem cells in CNS disease models, focusing on the models of EAE and describe the advantages and disadvantages of each stem cell type for future clinical applications in MS. PMID- 17868018 TI - Multiple sclerosis findings in the spinal cord. AB - The spinal cord is commonly affected by acute demyelinating lesions, chronic tissue loss and atrophy in multiple sclerosis, and is a clinically eloquent site. Historically, however, more attention has been focussed on the analysis and contribution of brain lesions. In this review, we discuss some of the key findings from MRI analysis and histopathological examination of the spinal cord, and how they relate to the clinical characteristics of this common and disabling disease. PMID- 17868019 TI - Multiple sclerosis symptom management. AB - Multiple sclerosis (MS) is the most common cause of nontraumatic disability in young adults. The increasing emphasis on early treatment with disease-modifying therapies has the goal of preventing long-term disability. However, current disease treatments are only partially effective, and most patients experience a variety of neurologic symptoms at various times during their disease course. Because these symptoms often have a profound impact on social, occupational and physical performance, effective symptom management is an important component of therapy to maintain quality of life. Effective symptom management often requires a multidisciplinary team approach. This review outlines general principles of the management of MS symptoms. PMID- 17868020 TI - A prototype software methodology for the rapid evaluation of biomanufacturing process options. AB - A three-layered simulation methodology is described that rapidly evaluates biomanufacturing process options. In each layer, inferior options are screened out, while more promising candidates are evaluated further in the subsequent, more refined layer, which uses more rigorous models that require more data from time-consuming experimentation. Screening ensures laboratory studies are focused only on options showing the greatest potential. To simplify the screening, outputs of production level, cost and time are combined into a single value using multi-attribute-decision-making techniques. The methodology was illustrated by evaluating alternatives to an FDA (U.S. Food and Drug Administration)-approved process manufacturing rattlesnake antivenom. Currently, antivenom antibodies are recovered from ovine serum by precipitation/centrifugation and proteolyzed before chromatographic purification. Alternatives included increasing the feed volume, replacing centrifugation with microfiltration and replacing precipitation/centrifugation with a Protein G column. The best alternative used a higher feed volume and a Protein G step. By rapidly evaluating the attractiveness of options, the methodology facilitates efficient and cost-effective process development. PMID- 17868021 TI - Pollen-mediated transformation of Sorghum bicolor plants. AB - Pollen from sorghum (Sorghum bicolor L. Moench) were transformed by a novel genetic transformation approach using mild ultrasonication. The plasmid pBI121 contained the NPT II gene encoding NPT II (neomycin phosphotransferase II) and a GUS (beta-glucuronidase) reporter gene. Plasmid DNA and pollen from sorghum A(2)V4B were submerged in a 0.3 mol/l sucrose solution and then subjected to ultrasonication. The treated pollen was then used for pollination of stigmas from the male sterile line A(2)V4A. Detection of transient and stable GUS activity confirmed that the GUS gene was expressed in transgenic plants. PCR amplification and Southern-blot analysis of transgenic plants confirmed that the NPT II gene had been integrated into the sorghum genome. These results indicate that direct gene transfer to pollen can be mediated by mild ultrasonication. PMID- 17868022 TI - Enhancing methacrylate-monolith-based downstream processes to champion plasmid DNA production. AB - Increasing numbers of preclinical and clinical studies are utilizing pDNA (plasmid DNA) as the vector. In addition, there has been a growing trend towards larger and larger doses of pDNA utilized in human trials. The growing demand on pDNA manufacture leads to pressure to make more in less time. A key intervention has been the use of monoliths as stationary phases in liquid chromatography. Monolithic stationary phases offer fast separation to pDNA owing to their large pore size, making pDNA in the size range from 100 nm to over 300 nm easily accessible. However, the convective transport mechanism of monoliths does not guarantee plasmid purity. The recovery of pure pDNA hinges on a proper balance in the properties of the adsorbent phase, the mobile phase and the feedstock. The effects of pH and ionic strength of binding buffer, temperature of feedstock, active group density and the pore size of the stationary phase were considered as avenues to improve the recovery and purity of pDNA using a methacrylate-based monolithic adsorbent and Escherichia coli DH5 alpha-pUC19 clarified lysate as feedstock. pDNA recovery was found to be critically dependent on the pH and ionic strength of the mobile phase. Up to a maximum of approx. 92% recovery was obtained under optimum conditions of pH and ionic strength. Increasing the feedstock temperature to 80 degrees C increased the purity of pDNA owing to the extra thermal stability associated with pDNA over contaminants such as proteins. Results from toxicological studies of the plasmid samples using endotoxin standard (E. coli 0.55:B5 lipopolysaccharide) show that endotoxin level decreases with increasing salt concentration. It was obvious that large quantities of pure pDNA can be obtained with minimal extra effort simply by optimizing process parameters and conditions for pDNA purification. PMID- 17868023 TI - Characterization of a human telomerase reverse transcriptase sequence containing two antigenic epitopes with high affinity for human leucocyte antigen. AB - Almost all human malignant tumours exhibit strong telomerase activity, but normal adult tissues, with a few exceptions, do not. hTERT (human telomerase reverse transcriptase) is an essential component of telomerase, and hence it can serve as a parallel sign in the diagnosis and prognosis of cancers. In the present study, we selected a sequence of hTERT containing two antigenic epitopes that have high affinity for HLA-A2 (human leucocyte antigen-A2) as a TAA (tumour-associated antigen) based on a peptide-motif scoring system. The sequence was obtained by reverse-transcriptase PCR and cloned into the Escherichia coli expression vector pGEX-4T-1. The expression product appeared in the form of inclusion bodies. Denatured inclusion-body extract was subjected to SDS/PAGE, and the gel band corresponding to the putative 38 kDa fusion protein (GST-hTERT major tumour associated antigen) was excised, ground with PBS, mixed with Freund's adjuvant and used to inoculate mice, generating anti-TERT polyclonal antibodies. Western blotting using the leukaemia cell line THP-1 demonstrated that the antibodies were able to detect hTERT expression, implying the potential applicability of the antigenic peptides derived from hTERT as a universal marker in the diagnosis and prognosis of tumours. PMID- 17868024 TI - Expression of human coagulation Factor IX in transgenic tomato (Lycopersicon esculentum). AB - In the present study, a plant binary expression vector PG-pRD12-hFIX (where PG is polygalacturonase) harbouring the hFIX (human coagulation Factor IX) gene was constructed and introduced into tomato (Lycopersicon esculentum) via Agrobacterium tumefaciens-mediated transformation. After kanamycin selection, 32 putative independent transgenic tomato plants were regenerated. PCR and Southern blot analyses confirmed the transgenic status of some plants. RT (reverse transcription)-PCR analysis for the expression of the introduced gene (hFIX) demonstrated that the hFIX gene was expressed specifically in fruits of the tomato. Western-blot analysis confirmed the presence of a 56 kDa band specific to hFIX in the transformed tomatoes. ELISA results showed that the expression of hFIX protein reached a maximum of 15.84 ng/g fresh weight in mature fruit. A blood-clotting assay demonstrated the clotting activity of the expressed hFIX protein in transgenic tomato fruits. This is the first report on the expression of hFIX in plants, and our research provides potentially valuable knowledge for further development of the plant-derived therapeutic proteins. PMID- 17868025 TI - Antitumour activity of cationic-liposome-conjugated adenovirus containing the CCL19 [chemokine (C-C motif) ligand 19] gene. AB - CCL19 [chemokine (C-C motif) ligand 19; also known as MIP-3beta (macrophage inflammatory protein-3beta) or ELC (Epstein-Barr-virus-induced molecule 1 ligand chemokine)], one of the immunostimulatory cytokines, chemoattracts both DCs (dendritic cells) and T-lymphocytes. Adenoviral vector is one of the most used gene delivery vectors for cancer therapy because of its high gene-transfection efficiency. However, its wider application is limited, owing to immune responses that reduce transgene expression and decrease the efficacy of repeated administration. We constructed the recombinant replication deficient adenoviral vectors containing the CCL19 gene (Ad-CCL19) and combined them with PEG-PE [poly(ethylene glycol)-phosphatidylethanolamine]-modified cationic liposomes (Ad CCL19/PEG-PE) for immunotherapy against murine fibrosarcoma. Although there were hardly any therapeutic differences between Ad-CCL19- and Ad-CCL19/PEG-PE-treated mice that were observed at the second administration, the final results demonstrated that Ad-CCL19/PEG-PE-treated mice survived much longer. The antitumour efficacy may be related to the high level of CCL19 after the final administration and lasting expression of IFN-gamma (interferon-gamma) and IL-12 (interleukin-12) in the Ad-CCL19/PEG-PE-treated group, which were measured by reverse-transcription PCR and ELISA. The results demonstrated that PEG-PE cationic-liposome-conjugated adenovirus could prolong the expression of the therapeutic gene in vivo and may enhance the antitumour efficacy. PMID- 17868026 TI - Breakthrough performance of large proteins on ion-exchange membrane columns. AB - Protein adsorption of large proteins on ion-exchange membrane columns was theoretically and experimentally investigated using batch and fixed-bed systems. Thyroglobulin was used as the model protein. The study strongly suggests that part of the protein is physically retained inside the column during frontal mode operation. These experimental results were used to obtain a filtration function of the chromatographic system. In the theoretical analysis of the frontal protein adsorption, a model was integrated by the serial coupling of the membrane transport model, the filtration model and the system-dispersion model. Two different techniques were employed in the estimation of the maximum adsorption capacity, the equilibrium desorption constant and the forward interaction rate constant, which are the parameters of the membrane-transport model. The fit of the model to the experimental data was not possible using the equilibrium parameters obtained in the batch experiments. The parameter estimation using a simplex optimization routine coupled to the solution of the partial differential model equations yields full prediction of the adsorption phenomena. PMID- 17868027 TI - G1 phase-dependent nucleolar accumulation of human histone H1x. AB - BACKGROUND INFORMATION: H1 histones are a protein family comprising several subtypes. Although specific functions of the individual subtypes could not be determined so far, differential roles are indicated by varied nuclear distributions as well as differential expression patterns of the H1 subtypes. Although the group of replication-dependent H1 subtypes is synthesized during S phase, the replacement H1 subtype, H1 degrees , is also expressed in a replication-independent manner in non-proliferating cells. Recently we showed, by protein biochemical analysis, that the ubiquitously expressed subtype H1x is enriched in the micrococcal nuclease-resistant part of chromatin and that, although it shares common features with H1 degrees , its expression is differentially regulated, since, in contrast to H1 degrees , growth arrest or induction of differentiation did not induce an accumulation of H1x. RESULTS: In the present study, we show that H1x exhibits a cell-cycle-dependent change of its nuclear distribution. This H1 subtype showed a nucleolar accumulation during the G(1) phase, and it was evenly distributed in the nucleus during S phase and G(2). Immunocytochemical analysis of the intranucleolar distribution of H1x indicated that it is located mainly in the condensed nucleolar chromatin. In addition, we demonstrate that the amount of H1x protein remained nearly unchanged during S phase progression, which is in contrast to the replication-dependent subtypes. CONCLUSION: These results suggest that the differential localization of H1x provides a mechanism for a control of H1x activity by means of shuttling between nuclear subcompartments instead of a controlled turnover of the protein. PMID- 17868028 TI - Retention and mobility of the mammalian lamin B receptor in the plant nuclear envelope. AB - BACKGROUND INFORMATION: In a previous study, we showed that GFP (green fluorescent protein) fused to the N-terminal 238 amino acids of the mammalian LBR (lamin B receptor) localized to the NE (nuclear envelope) when expressed in the plant Nicotiana tabacum. The protein was located in the NE during interphase and migrated with nuclear membranes during cell division. Targeting and retention of inner NE proteins requires several mechanisms: signals that direct movement through the nuclear pore complex, presence of a transmembrane domain or domains and retention by interaction with nuclear or nuclear-membrane constituents. RESULTS: Binding mutants of LBR-GFP were produced to investigate the mechanisms for the retention of LBR in the NE. FRAP (fluorescence recovery after photobleaching) analysis of mutant and wild-type constructs was employed to examine the retention of LBR-GFP in the plant NE. wtLBR-GFP (wild-type LBR-GFP) was shown to have significantly lower mobility in the NE than the lamin-binding domain deletion mutant, which showed increased mobility in the NE and was also localized to the endoplasmic reticulum and punctate structures in some cells. Modification of the chromatin-binding domain resulted in the localization of the protein in nuclear inclusions, in which it was immobile. CONCLUSIONS: As expression of truncated LBR-GFP in plant cells results in altered targeting and retention compared with wtLBR-GFP, we conclude that plant cells can recognize the INE (inner NE)-targeting motif of LBR. The altered mobility of the truncated protein suggests that not only do plant cells recognize this signal, but also have nuclear proteins that interact weakly with LBR. PMID- 17868029 TI - AF10-dependent transcription is enhanced by its interaction with FLRG. AB - BACKGROUND INFORMATION: FLRG (follistatin-related gene) is a secreted glycoprotein which is very similar to follistatin. As observed for follistatin, FLRG is involved in the regulation of various biological processes through its binding to members of the TGFbeta (transforming growth factor beta) superfamily, activin, BMPs (bone morphogenetic proteins) and myostatin. Unlike follistatin, FLRG has been found to be both secreted and localized within the nucleus of many FLRG-producing cells, suggesting the existence of specific intracellular functions of the protein. RESULTS: In order to analyse the function of the nuclear form of FLRG, we performed a yeast two-hybrid screen, in which we identified AF10 [ALL1 (acute lymphoblastic leukaemia) fused gene from chromosome 10], a translocation partner of the MLL (mixed-lineage leukaemia) oncogene in human leukaemia, as a FLRG-interacting protein. This interaction was confirmed by far-Western-blot analysis and co-immunoprecipitation with transfected COS-7 cells. The N-terminal region of AF10, including the PHD (plant homeodomain), is sufficient to mediate this interaction, and has been shown to be involved in AF10 homo-oligomerization. By immunoprecipitation experiments, we showed that FLRG enhances the homo-oligomerization of AF10. Functional studies demonstrated that FLRG enhances the transactivation properties of the AF10 protein fused to Gal4 DNA-binding domains in transient transfection assays. CONCLUSIONS: Our present study provides novel insights into the function of the nuclear form of the FLRG protein, which is revealed as a novel regulator of transcription. The nuclear isoform of FLRG lacks an intrinsic transactivation domain, but enhances AF10 mediated transcription, probably through promoting the homo-oligomerization of AF10, thus facilitating the recruitment of co-activators. PMID- 17868030 TI - RNA interference of metastasis-associated gene 1 inhibits metastasis of B16F10 melanoma cells in a C57BL/6 mouse model. AB - BACKGROUND INFORMATION: MTA1 (metastasis-associated gene 1) has been reported to be overexpressed in cancers with high potential to metastasize. Studies of the molecular mechanisms revealed that MTA1 plays an important role in the process of metastasis of many types of cancer. However, the role of MTA1 in melanoma development is unclear. RESULTS: We have investigated the therapeutic value of MTA1 in the B16F10 melanoma cell line with the C57BL/6 mouse model. Studies in vitro showed that MTA1 promoted the metastatic ability of B16F10 cancer cells. MTA1 down-regulation by RNA interference greatly reversed the malignant phenotypes of cancer cells. Immunohistochemical staining of MTA1 in human melanoma samples confirmed the up-regulation of MTA1 in the process of carcinogenesis. Studies in vivo confirmed down-regulation of MTA1 suppressed the growth and experimental metastasis of B16F10 melanoma cells. CONCLUSIONS: MTA1 plays an important role in melanoma development and metastasis. It has a promising potential as a target for in cancer gene therapy or chemotherapy. PMID- 17868031 TI - Arf GAPs as regulators of the actin cytoskeleton. AB - The Arf (ADP-ribosylation factor) GAPs (GTPase-activating proteins) are a family of proteins with a common catalytic domain that induces hydrolysis of GTP bound to Arf GTP-binding proteins. At least three groups of multidomain Arf GAPs affect the actin cytoskeleton and cellular activities, such as migration and movement, that depend on the cytoskeleton. One role of the Arf GAPs is to regulate membrane remodelling that accompanies actin polymerization. Regulation of membrane remodelling is mediated in part by the regulation of Arf proteins. However, Arf GAPs also regulate actin independently of effects on membranes or Arf. These functions include acting as upstream regulators of Rho family proteins and providing a scaffold for Rho effectors and exchange factors. With multiple functional elements, the Arf GAPs could integrate signals and biochemical activities that result in co-ordinated changes in actin and membranes necessary for a wide range of cellular functions. PMID- 17868032 TI - Caspase-3-truncated type 1 inositol 1,4,5-trisphosphate receptor enhances intracellular Ca2+ leak and disturbs Ca2+ signalling. AB - BACKGROUND INFORMATION: The IP(3)R (inositol 1,4,5-trisphosphate receptor) is a tetrameric channel that accounts for a large part of the intracellular Ca(2+) release in virtually all cell types. We have previously demonstrated that caspase 3-mediated cleavage of IP(3)R1 during cell death generates a C-terminal fragment of 95 kDa comprising the complete channel domain. Expression of this truncated IP(3)R increases the cellular sensitivity to apoptotic stimuli, and it was postulated to be a constitutively active channel. RESULTS: In the present study, we demonstrate that expression of the caspase-3-cleaved C-terminus of IP(3)R1 increased the rate of thapsigargin-mediated Ca(2+) leak and decreased the rate of Ca(2+) uptake into the ER (endoplasmic reticulum), although it was not sufficient by itself to deplete intracellular Ca(2+) stores. We detected the truncated IP(3)R1 in different cell types after a challenge with apoptotic stimuli, as well as in aged mouse oocytes. Injection of mRNA corresponding to the truncated IP(3)R1 blocked sperm factor-induced Ca(2+) oscillations and induced an apoptotic phenotype. CONCLUSIONS: In the present study, we show that caspase-3-mediated truncation of IP(3)R1 enhanced the Ca(2+) leak from the ER. We suggest a model in which, in normal conditions, the increased Ca(2+) leak is largely compensated by enhanced Ca(2+)-uptake activity, whereas in situations where the cellular metabolism is compromised, as occurring in aging oocytes, the Ca(2+) leak acts as a feed-forward mechanism to divert the cell into apoptosis. PMID- 17868033 TI - Determination of the class and isoform selectivity of small-molecule histone deacetylase inhibitors. AB - The human HDAC (histone deacetylase) family, a well-validated anticancer target, plays a key role in the control of gene expression through regulation of transcription. While HDACs can be subdivided into three main classes, the class I, class II and class III HDACs (sirtuins), it is presently unclear whether inhibiting multiple HDACs using pan-HDAC inhibitors, or targeting specific isoforms that show aberrant levels in tumours, will prove more effective as an anticancer strategy in the clinic. To address the above issues, we have tested a number of clinically relevant HDACis (HDAC inhibitors) against a panel of rhHDAC (recombinant human HDAC) isoforms. Eight rhHDACs were expressed using a baculoviral system, and a Fluor de Lystrade mark (Biomol International) HDAC assay was optimized for each purified isoform. The potency and selectivity of ten HDACs on class I isoforms (rhHDAC1, rhHDAC2, rhHDAC3 and rhHDAC8) and class II HDAC isoforms (rhHDAC4, rhHDAC6, rhHDAC7 and rhHDAC9) was determined. MS-275 was HDAC1-selective, MGCD0103 was HDAC1- and HDAC2-selective, apicidin was HDAC2- and HDAC3-selective and valproic acid was a specific inhibitor of class I HDACs. The hydroxamic acid-derived compounds (trichostatin A, NVP-LAQ824, panobinostat, ITF2357, vorinostat and belinostat) were potent pan-HDAC inhibitors. The growth inhibitory effect of the HDACis on HeLa cells showed that both pan-HDAC and class I-specific inhibitors inhibited cell growth. The results also showed that both pan-HDAC and class-I-specific inhibitor treatment resulted in increased acetylation of histones, but only pan-HDAC inhibitor treatment resulted in increased tubulin acetylation, which is in agreement with their activity towards the HDAC6 isoform. PMID- 17868034 TI - The covalent modification and regulation of TLR8 in HEK-293 cells stimulated with imidazoquinoline agonists. AB - The mammalian TLRs (Toll-like receptors) mediate the rapid initial immune response to pathogens through recognition of pathogen-associated molecular patterns. The pathogen pattern to which TLR8 responds is ssRNA (single-stranded RNA) commonly associated with ssRNA viruses. TLR8 also responds to small, purine like molecules including the imidazoquinoline IRMs (immune-response modifiers). The IRMs include molecules that selectively activate TLR7, selectively activate TLR8 or non-selectively activate both TLR7 and TLR8. Using HEK-293 cells (human embryonic kidney cells) stably expressing an NF-kappaB (nuclear factor kappaB)/luciferase promoter-reporter system as a model system, we have examined the regulation of TLR8 using the non-selective TLR7/8 agonist, 3M-003. Using conservative tyrosine to phenylalanine site-directed mutation, we show that of the 13 tyrosine residues resident in the cytosolic domain of TLR8, only three appear to be critical to TLR8 signalling. Two of these, Tyr898 and Tyr904, reside in the Box 1 motif and the third, Tyr1048, lies in a YXXM putative p85-binding motif. TLR8 is tyrosine-phosphorylated following 3M-003 treatment and TLR8 signalling is inhibited by tyrosine kinase inhibitors. Treatment with 3M-003 results in the association of the p85 regulatory subunit of PI3K (phosphoinositide 3-kinase) with TLR8 and this association is inhibited by tyrosine to phenylalanine mutation of either the YXXM or Box 1 motifs. As a further consequence of activation by 3M-003, TLR8 is modified to yield both higher and lower molecular mass species. These species include a monoubiquitinated form as deduced from ubiquitin peptide sequencing by HPLC/MS/MS (tandem MS). PMID- 17868035 TI - Human group III secreted phospholipase A2 promotes neuronal outgrowth and survival. AB - Human sPLA2-III [group III secreted PLA2 (phospholipase A2)] is an atypical sPLA2 isoenzyme that consists of a central group III sPLA2 domain flanked by unique N- and C-terminal domains. In the present study, we found that sPLA2-III is expressed in neuronal cells, such as peripheral neuronal fibres, spinal DRG (dorsal root ganglia) neurons and cerebellar Purkinje cells. Adenoviral expression of sPLA2-III in PC12 cells (pheochromocytoma cells) or DRG explants facilitated neurite outgrowth, whereas expression of a catalytically inactive sPLA2-III mutant or use of sPLA2-III-directed siRNA (small interfering RNA) reduced NGF (nerve growth factor)-induced neuritogenesis. sPLA2-III also suppressed neuronal death induced by NGF deprivation. Lipid MS revealed that sPLA2-III overexpression increased the cellular level of lysophosphatidylcholine, a PLA2 reaction product with neuritogenic and neurotropic activities, whereas siRNA knockdown reduced the level of lysophosphatidylcholine. These observations suggest the potential contribution of sPLA2-III to neuronal differentiation and its function under certain conditions. PMID- 17868036 TI - Imatinib mesylate improves insulin sensitivity and glucose disposal rates in rats fed a high-fat diet. AB - The aim of the present study was to investigate whether imatinib affects insulin sensitivity and glucose disposal in HF (high-fat)-fed rats. Sprague-Dawley rats were fed either a standard pelleted rat food (low-fat diet) or an HF diet (60% fat) for 8 weeks. During the last 10 days of the HF diet regime, rats received saline alone or imatinib (50 or 100 mg/kg of body weight) daily by gavage. The higher dose of imatinib resulted in a decreased psoas fat pad weight in the HF treated rats. Under euglycaemic hyperinsulinaemic clamp conditions, HF-fed rats exhibited increased insulin concentrations and decreased glucose disposal. The lower (50 mg/kg of body weight), but not the higher (100 mg/kg of body weight), dose of imatinib normalized insulin sensitivity and glucose disposal without affecting glucose metabolism in low-fat-fed rats. Hepatic glucose production at both fasting and hyperinsulinaemic conditions was only weakly affected by imatinib. We conclude that a moderate dose of imatinib efficiently counteracts HF induced peripheral insulin resistance, and that further studies on the mechanisms by which imatinib increases insulin action in muscle and fat tissues might generate novel strategies for the treatment of Type 2 diabetes. PMID- 17868037 TI - Non-HDL cholesterol and apoB in dyslipidaemia. AB - On the basis of a high correlation, non-HDL-C (non-high-density lipoprotein cholesterol) and apoB (apolipoprotein B) have been suggested to be of equivalent value for clinical practice; however, the strength of this relationship has not been examined in detail in patients with dyslipidaemia. The present study examines the variance of non-HDL-C compared with apoB in 1771 consecutive patients evaluated in a lipid clinic. These patients were divided into normolipidaemic subjects (n=407), type I hyperlipoproteinaemia (n=16), type IIa (n=736) and IIb (n=231) hyperlipoproteinaemia, type III hyperlipoproteinaemia (n=38), type IV hyperlipoproteinaemia (n=509) and type V hyperlipoproteinaemia (n=101). The relationship between non-HDL-C and apoB was examined both in terms of correlation and concordance. Correlation was high, but concordance was only moderate in the normolipidaemic subjects and in those with type IIa and type IIb hyperlipoproteinaemia. Correlation and concordance were both low in the subgroups with type III and type V hyperlipoproteinaemia. In those with type IV hyperlipoproteinaemia, correlation was moderately high (r=0.74), but concordance was only fair. In conclusion, our results indicate that there is substantial variance of apoB for given values of non-HDL-C in many dyslipidaemic subjects. It follows that correlation is not adequate as a sole judge of equivalence of laboratory parameters. PMID- 17868038 TI - Kinetic and biochemical characterization of Plasmodium falciparum GMP synthetase. AB - Plasmodium falciparum, the causative agent of the fatal form of malaria, synthesizes GMP primarily from IMP and, hence, needs active GMPS (GMP synthetase) for its survival. GMPS, a G-type amidotransferase, catalyses the amination of XMP to GMP with the reaction occurring in two domains, the GAT (glutamine amidotransferase) and ATPPase (ATP pyrophosphatase). The GAT domain hydrolyses glutamine to glutamate and ammonia, while the ATPPase domain catalyses the formation of the intermediate AMP-XMP from ATP and XMP. Co-ordination of activity across the two domains, achieved through channelling of ammonia from GAT to the effector domain, is the hallmark of amidotransferases. Our studies aimed at understanding the kinetic mechanism of PfGMPS (Plasmodium falciparum GMPS) indicated steady-state ordered binding of ATP followed by XMP to the ATPPase domain with glutamine binding in a random manner to the GAT domain. We attribute the irreversible, Ping Pong step seen in initial velocity kinetics to the release of glutamate before the attack of the adenyl-XMP intermediate by ammonia. Specific aspects of the overall kinetic mechanism of PfGMPS are different from that reported for the human and Escherichia coli enzymes. Unlike human GMPS, absence of tight co-ordination of activity across the two domains was evident in the parasite enzyme. Variations seen in the inhibition by nucleosides and nucleotide analogues between human GMPS and PfGMPS highlighted differences in ligand specificity that could serve as a basis for the design of specific inhibitors. The present study represents the first report on recombinant His tagged GMPS from parasitic protozoa. PMID- 17868039 TI - Functional complementation of high-efficiency resonance energy transfer: a new tool for the study of protein binding interactions in living cells. AB - Green bioluminescence in Renilla species is generated by a approximately 100% efficient RET (resonance energy transfer) process that is caused by the direct association of a blue-emitting luciferase [Rluc (Renilla luciferase)] and an RGFP (Renilla green fluorescent protein). Despite the high efficiency, such a system has never been evaluated as a potential reporter of protein-protein interactions. To address the question, we compared and analysed in mammalian cells the bioluminescence of Rluc and RGFP co-expressed as free native proteins, or as fused single-chain polypeptides and tethered partners of self-assembling coiled coils. Here, we show that: (i) no spontaneous interactions generating detectable BRET (bioluminescence RET) signals occur between the free native proteins; (ii) high-efficiency BRET similar to that observed in Renilla occurs in both fusion proteins and self-interacting chimaeras, but only if the N-terminal of RGFP is free; (iii) the high-efficiency BRET interaction is associated with a dramatic increase in light output when the luminescent reaction is triggered by low quantum yield coelenterazine analogues. Here, we propose a new functional complementation assay based on the detection of the high-efficiency BRET signal that is generated when the reporters Rluc and RGFP are brought into close proximity by a pair of interacting proteins to which they are linked. To demonstrate its performance, we implemented the assay to measure the interaction between GPCRs (G-protein-coupled receptors) and beta-arrestins. We show that complementation-induced BRET allows detection of the GPCR-beta-arrestin interaction in a simple luminometric assay with high signal-to-noise ratio, good dynamic range and rapid response. PMID- 17868040 TI - Glucosylated free oligosaccharides are biomarkers of endoplasmic- reticulum alpha glucosidase inhibition. AB - The inhibition of ER (endoplasmic reticulum) alpha-glucosidases I and II by imino sugars, including NB-DNJ (N-butyl-deoxynojirimycin), causes the retention of glucose residues on N-linked oligosaccharides. Therefore, normal glycoprotein trafficking and processing through the glycosylation pathway is abrogated and glycoproteins are directed to undergo ERAD (ER-associated degradation), a consequence of which is the production of cytosolic FOS (free oligosaccharides). Following treatment with NB-DNJ, FOS were extracted from cells, murine tissues and human plasma and urine. Improved protocols for analysis were developed using ion-exchange chromatography followed by fluorescent labelling with 2-AA (2 aminobenzoic acid) and purification by lectin-affinity chromatography. Separation of 2-AA-labelled FOS by HPLC provided a rapid and sensitive method that enabled the detection of all FOS species resulting from the degradation of glycoproteins exported from the ER. The generation of oligosaccharides derived from glucosylated protein degradation was rapid, reversible, and time- and inhibitor concentration-dependent in cultured cells and in vivo. Long-term inhibition in cultured cells and in vivo indicated a slow rate of clearance of glucosylated FOS. In mouse and human urine, glucosylated FOS were detected as a result of transrenal excretion and provide unique and quantifiable biomarkers of ER glucosidase inhibition. PMID- 17868041 TI - Development of SCAR (sequence-characterized amplified region) markers as a complementary tool for identification of ginger (Zingiber officinale Roscoe) from crude drugs and multicomponent formulations. AB - Zingiber officinale Roscoe (common or culinary ginger) is an official drug in Ayurvedic, Indian herbal, Chinese, Japanese, African and British Pharmacopoeias. The objective of the present study was to develop DNA-based markers that can be applied for the identification and differentiation of the commercially important plant Z. officinale Roscoe from the closely related species Zingiber zerumbet (pinecone, bitter or 'shampoo' ginger) and Zingiber cassumunar [cassumunar or plai (Thai) ginger]. The rhizomes of the other two Zingiber species used in the present study are morphologically similar to that of Z. officinale Roscoe and can be used as its adulterants or contaminants. Various methods, including macroscopy, microscopy and chemoprofiling, have been reported for the quality control of crude ginger and its products. These methods are reported to have limitations in distinguishing Z. officinale from closely related species. Hence, newer complementary methods for correct identification of ginger are useful. In the present study, RAPD (random amplification of polymorphic DNA) analysis was used to identify putative species-specific amplicons for Z. officinale. These were further cloned and sequenced to develop SCAR (sequence-characterized amplified region) markers. The developed SCAR markers were tested in several non Zingiber species commonly used in ginger-containing formulations. One of the markers, P3, was found to be specific for Z. officinale and was successfully applied for detection of Z. officinale from Trikatu, a multicomponent formulation. PMID- 17868042 TI - How robust is the optic chiasm? Perimetric and neuro-imaging correlations. AB - OBJECTIVES: Analysis of form and function relationships with tumour-mediated dislocations and deformations of the optic chiasm. MATERIALS AND METHODS: Results of magnetic resonance tomography and two forms of quantitative, computerized perimetry were contrasted in 31 patients with pituitary adenomata impinging on the chiasm, prior to treatment. RESULTS: Perimetric abnormalities ranged from none to modest. High-pass Resolution Perimetry (HRP) produced abnormal results in 10 cases and RareBit perimetry (RBP) in 15 cases. Overall, field defects and qualitative stages of deformation and dislocation of the chiasm were well correlated. Among quantitative indices, the best correlations were obtained by a measure of the cranio-caudal position of the chiasm. CONCLUSIONS: On average, an elevation of the chiasm by 6 mm will be associated with abnormal visual fields in 50% of the cases. An additional elevation of 5 mm will raise the incidence of field defects to 90%. PMID- 17868043 TI - The contribution of alpha(2)-macroglobulin thrombin to the endogenous thrombin potential. PMID- 17868044 TI - Paravertebral extramedullary haemopoiesis occurring in a case of congenital dyserythropoietic anaemia type II. PMID- 17868045 TI - Bi-clonal disease in patients with chronic lymphocytic leukaemia as detected by analysing IGHV mutation status. PMID- 17868046 TI - Association of autoimmune disease-related gene polymorphisms with chronic graft versus-host disease. AB - Chronic graft-versus-host disease (GVHD) is the most common cause of poor outcomes after haematopoietic stem cell transplantation (HSCT), while the pathophysiology of chronic GVHD remains poorly understood. As both chronic GVHD and autoimmune disease share clinical features, we speculated that autoimmune disease-related genes might be candidate chronic GVHD-related genes. Recent large scale cohort studies showed that Fc receptor-like 3 gene (FCRL3) single nucleotide polymorphism (SNP) and peptidylarginine deiminases citrullinating enzymes 4 gene (PADI4) haplotype were associated with autoimmune disease. The present study investigated the association between polymorphisms of these two genes and the incidence of chronic GVHD. We analysed 123 cases of Japanese human leucocyte antigen-matched sibling recipients and their donors who underwent HSCT. Although PADI4, which is the rheumatoid arthritis-specific related gene, was not associated with the occurrence of chronic GVHD, the recipient FCRL3-169C/C genotype was significantly less frequent in chronic GVHD patients than in those without chronic GVHD (P = 0.0086). There was no relationship between FCRL3 polymorphism and acute GVHD. As FCRL3 is expressed by B cells and might have an important role in immunoregulation, this significant protective genetic effect raises the question of whether FCRL3 might also be involved in the pathogenesis of chronic GVHD. PMID- 17868047 TI - Clinical characteristics and treatment outcome of infants with non-Hodgkin lymphoma. AB - Non-Hodgkin lymphoma (NHL) is rarely observed during infancy and data on its incidence, characteristics and outcome are scarce. The present study aimed to assess the prevalence, clinical presentation and treatment results of all infants who were diagnosed with NHL between October 1986 and December 2002 among 2084 patients treated according to the NHL-BFM (Berlin-Frankfurt-Munster) multicentre trials 86, 90 and 95. We identified 20 (1%) infants with NHL including five with T-cell lymphoblastic lymphoma (T-cell LBL), seven with precursor B-cell LBL (pB cell LBL), two with a mature Burkitt neoplasm, five with anaplastic large cell lymphoma (ALCL) and one with peripheral T-cell lymphoma (PTCL). The PTCL patient, 3/7 pB-cell LBL and 1/5 ALCL patients relapsed. One patient each from the T-cell LBL and Burkitt lymphoma groups suffered from a second malignancy and one patient each with ALCL and Burkitt leukaemia died from treatment-related toxicity. The 5 year event-free survival rate was 53 +/- 12% for the 20 cases. This study has provided preliminary evidence that infants with NHL have a dismal prognosis and showed that infant NHL differed to lymphomas in older patients with respect to the distribution of gender, histopathologic subtypes as well as the ratio of T- to pB-cell LBL and the frequency of relapses of pB-cell LBL. PMID- 17868048 TI - Inhibitory mechanisms of resveratrol in platelet activation: pivotal roles of p38 MAPK and NO/cyclic GMP. AB - Resveratrol has been reported to have antiplatelet activity; however, the detailed mechanisms have not yet been resolved. This study aimed to systematically examine the detailed mechanisms of resveratrol in the prevention of platelet activation in vitro and in vivo. Resveratrol (0.05-0.25 micromol/l) showed stronger inhibition of platelet aggregation stimulated by collagen (1 microg/ml) than other agonists. Resveratrol (0.15 and 0.25 micromol/l) inhibited collagen-induced platelet activation accompanied by [Ca(+2)]i mobilization, thromboxane A(2) (TxA(2)) formation, phosphoinositide breakdown, and protein kinase C (PKC) activation. Resveratrol markedly increased levels of NO/cyclic guanosine monophosphate (GMP), and cyclic GMP-induced vasodilator-stimulated phosphoprotein phosphorylation. Resveratrol markedly inhibited p38 mitogen activated protein kinase (MAPK) but not Jun N-terminal kinase or extracellular signal-regulated kinase-2 phosphorylation in washed platelets. Resveratrol reduced hydroxyl radical (OH(-)) formation in the electron spin resonance study. In an in vivo study, resveratrol (5 mg/kg) significantly prolonged platelet plug formation of mice. In conclusion, the main findings of this study suggest that the inhibitory effects of resveratrol possibly involve (i) inhibition of the p38 MAPK-cytosolic phospholipase A(2)-arachidonic acid-TxA(2)-[Ca(+2)]i cascade and (ii) activation of NO/cyclic GMP, resulting in inhibition of phospholipase C and/or PKC activation. Resveratrol is likely to exert significant protective effects in thromboembolic-related disorders by inhibiting platelet aggregation. PMID- 17868049 TI - Surgery for medically intractable temporal lobe epilepsy during early life. AB - PURPOSE: Temporal lobe epilepsy (TLE) in early life is often a catastrophic disorder with pharmacoresistant seizures and secondary neurological deterioration. there is little data available regarding epilepsy surgery performed in infants and young children and no prior study has focused on tle. METHODS: We analyzed the results of temporal resection for epilepsy as the primary indication in children less than age 5 years who had at least 2 years of follow-up. RESULTS: 20 children (14 males) were identified with a mean age at surgery of 26 months and a mean age at seizure onset of 12 months. Clinical presentation was diverse. Typical psychomotor seizures (n = 4; mean age at surgery 37 months) were followed by prominent motor changes (n = 7; 30 months) and were occasionally isolated (n = 3; 23 months). Epileptic spasms were noted in six patients and were frequently associated with lateralizing features. The interictal EEG was lateralizing in 15 patients and the ictal EEG was lateralizing in 18 patients. Brain MRI provided localizing value in 16 patients, ictal SPECT was concordant in 4/8 cases. Invasive EEG was employed in six cases. At mean follow-up of 5.5 years, 65% of the children were seizure-free and 15% had >90% seizure reduction. Morbidity included infection and hydrocephalus in one case and stroke-related hemiparesis in two cases. Cortical dysplasia was identified in eight children, tumors in eight including two DNET, two ganglioglioma, and four malignant tumors. Hippocampal sclerosis was present in four cases, always as dual pathology. CONCLUSION: TLE presents in early life with varied and severe manifestations. Excisional procedures in this age group are associated with favorable seizure reduction similar to older children and in adults. PMID- 17868050 TI - Hypotheses, tests, methods, and innovation: the balancing act in research. AB - Clinical and epidemiological research studies are essential to advancing our understanding of human health conditions such as epilepsy. To be of value, studies must not only address important questions, they must do so in such a way as to contribute usefully to existing knowledge. Comprehensive understanding of the subject matter is only one component of successful research and research reports. A firm grasp of research methods and statistical issues and a scholarly command of the relevant and current literature are essential components to high quality research. No single study, however, is perfect nor can any single study definitively answer a given single research question. Studies must be designed and evaluated in light of historical, scientific, pragmatic, and ethical realities that may constrain them. Selected but essential methodological and statistical concepts are discussed along with the need to balance innovation and novelty against methodological rigor. PMID- 17868051 TI - Focal reduction of neuronal glutamate transporters in human neocortical epilepsy. AB - PURPOSE: To study the differential expression of excitatory amino acid transporters (EAATs) at localized epileptic foci compared to nonepileptic regions in human neocortical epilepsy. Decreased expression of EAATs, the predominant mechanism to remove synaptic-released glutamate, may explain mechanisms of heightened excitability at these epileptic foci. METHODS: The differential expression of EAAT1-4 at the mRNA and protein levels was measured in electrically mapped human neocortical tissues using quantitative real-time PCR and immunoblotting. This required a novel way to prevent aggregation of EAAT proteins through cold solubilization. Layer-specific neuronal densities were measured to control for potential differences in neuronal density. RESULTS: While focal epileptic brain regions show marked increases in immediate early genes, they have significant reductions in the neuronal glutamate transporter mRNAs (EAAT3 and EAAT4). These changes were not associated with changes in relative neuronal density, suggesting a reduction in EAAT mRNA per neuron. Immunohistochemical staining of epileptic human neocortex confirmed the presence of EAAT1 and EAAT2 proteins in astroglial cells and EAAT3 and EAAT4 proteins in human cortical neurons. At the protein level, western blots of the same epileptic and nonepileptic regions for a subset of these patients showed a similar decrease of EAAT3 and EAAT4. Despite no change in EAAT2 mRNA, EAAT2 protein expression was significantly reduced at epileptic foci. CONCLUSION: Regional reductions in EAAT expression at human neocortical epileptic foci could produce increased local glutamate levels that in turn may contribute to both hyperexcitability and the spontaneous generation of epileptic discharges that characterize human epileptic foci. PMID- 17868052 TI - Pathways to discovery in epilepsy research: rethinking the quest for cures. AB - This paper, based on the 4th Annual Hoyer Lecture presented at the 2006 annual meeting of the American Epilepsy Society, first provides a general view of the current limitations in therapies aimed at achieving the goal of "no seizures, no side effects" for patients living with epilepsy. Some of the seminal discoveries in epilepsy research over the past 100 years are then reviewed, with an emphasis on the pivotal role of basic and clinical/translational science in leading the way to new and effective means for diagnosing and treating for epilepsy. The paper concludes with a view of the future course of epilepsy research. Scientific advances will increasingly rely on the collaboration of multidisciplinary teams of researchers using the analytic and storage capabilities of machines, and linked together by communication tools such as the Internet and related technologies. PMID- 17868053 TI - Protective effect of topiramate on kainic acid-induced cell death in mice hippocampus. AB - The protective effect of topiramate (TPM) on seizure-induced neuronal injury is well known; however, its molecular basis has yet to be elucidated. We investigated the effect and signaling mediators of TPM on seizure-induced hippocampal cell death in kainic acid (KA)-treated ICR mice. KA-induced hippocampal cell death was identified by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling. Immunoreactivity (IR) of p-Erk, p-Jnk, p-P38, and caspase-3, and caspase-3 activity were observed in the hippocampal region 3 h after KA (0.1 microg/5 microL, i.c.v.) administration, and/or TPM (100 mg/kg, i.p.) pretreatment. TPM attenuated seizure-induced neuronal cell death and reduced KA-induced p-Erk IR in the CA3 region of the hippocampus, but did not affect p-Jnk and p-P38. In addition, TPM reduced caspase-3 IR and activation by KA. KA-induced seizures were also suppressed by TPM pretreatment. TPM inhibits seizures, and decreases Erk phosphorylation and caspase-3 activation by KA, thereby contributing to protection from neuronal injury. PMID- 17868054 TI - The effectiveness of low-frequency stimulation for mapping cortical function. AB - OBJECTIVE: To establish the efficacy and safety of low-frequency electrical stimulation for cortical brain mapping. METHODS: Cortical function was mapped using electrical stimulation in epilepsy patients with chronically implanted intracranial subdural electrodes. Contacts overlying motor, sensory, visual, and language cortex were stimulated at frequencies of 5, 10, and 50 Hz, using current levels ranging from 1 to 17.5 mA for 3-5 s. The current intensity and incidence at which functional alterations and afterdischarges (ADs) occurred were recorded. The modified McNemar test for nonindependent measures was used to analyze the data. RESULTS: 122 electrode contact pairs were electrically stimulated at least two different frequencies in 14 patients. Functional alterations were obtained at all stimulation frequencies (5, 10, and 50 Hz) at generally similar rates. The likelihood of producing an AD correlated with stimulation frequency, and lower frequency stimulation was less likely to provoke an AD. Higher current intensity was required to induce both functional responses and ADs at low-frequency stimulation than high-frequency stimulation. While overall rates of producing functional changes were similar, differences in functional response with regard to frequency were noted at individual cortical sites. CONCLUSION: 5- and 10-Hz stimulation are as effective for mapping cortical function as 50-Hz stimulation and produce fewer ADs. We recommend that mapping of cortical function be started with 5-Hz-frequency stimulation. Higher frequencies should be used in suspect cortex if no symptoms or signs are produced with 5-Hz stimulation. PMID- 17868055 TI - Intralesional recordings and epileptogenic zone in focal polymicrogyria. AB - PURPOSE: Polymicrogyria (PMG) is recognized as an epileptogenic lesion but few data concerning organization of the epileptogenic zone (EZ) are available. METHODS: We analyzed the distribution of the EZ according to Stereo-EEG (SEEG) with intralesional recordings in four patients evaluated for intractable partial epilepsy associated with focal unilateral PMG, involving the posterior temporal region in two, the perisylvian area in one and the temporoparietal junction in the other. All had ictal scalp EEG, high-resolution structural and functional MRI, fluorodeoxyglucose positron emission tomography (FDG-PET), and SEEG. For each patient, several depth electrodes were implanted both within the PMG and in extralesional areas. RESULTS: In three patients, the PMG displayed high-frequency spiking activity. However, interictal and ictal recordings demonstrated a large epileptogenic network, which was more widespread than the PMG, including the mesial temporal structures in two. In another patient, interictal spiking and seizure onset site were located within the hippocampus and outside of the PMG, although it was rapidly involved during seizure spread. Overall, EZ was considered to be larger than the PMG in all patients although hypometabolic areas detected by PET were concordant with EZ. Three patients underwent extensive surgery including the PMG and are seizure free with a follow-up >2 years. DISCUSSION: Although intralesional recordings demonstrated intrinsic epileptogenicity in PMG, our data provide evidence that unilateral focal PMG belongs to a large epileptogenic network extending beyond the MRI lesion. SEEG may be helpful for planning surgery with favorable outcome, providing large resections are feasible, even in apparently focal PMG. PMID- 17868056 TI - Disappearance of tophi in familial juvenile hyperuricemic nephropathy after kidney transplantation. AB - A 40-year-old man who had been on hemodialysis for 25 months due to familial juvenile hyperuricemic nephropathy (FJHN) received a kidney transplant. Biopsy of his native kidney had shown tubulo-interstitial nephropathy. Genetic analysis confirmed abnormal uromodulin expression due to a mutation in the exon 4 of the UMOD gene. He had multiple tophi on the day of transplantation, including some on his fingers. He received immunosuppressive treatment including polyclonal antilymphocyte antibodies, mycophenolate mofetil, steroids and cyclosporine and achieved excellent renal function, with serum creatinine at 13 mg/L on day 10 posttransplantation and 9.4 mg/L at 6 months. His uric acid excretion rate increased from 4.4% at day 2 posttransplantation to 7.7% 6 months after transplantation. The number and sizes of the tophi were reduced 3 months posttransplantation, and nearly disappeared at month 6. Serum uric acid level decreased slowly from 650 mumol/L before transplantation to 300 mumol/L. Reduction of tophi was probably due to the absence of the mutated UMOD gene in the transplanted kidney. PMID- 17868057 TI - Sirolimus versus cyclosporine in kidney recipients receiving thymoglobulin, mycophenolate mofetil and a 6-month course of steroids. AB - To evaluate the efficacy and tolerance of a calcineurin inhibitor (CNI)-free regimen, 145 renal recipients were prospectively randomized to receive either sirolimus (n = 71) or cyclosporine (CsA; n = 74). All patients received polyclonal antilymphocyte antibodies, mycophenolate mofetil (MMF) and steroids (6 months). The primary endpoint, estimated glomerular filtration rate (eGFR) was not significantly different at 12 months comparing sirolimus- and CsA-treated patients (60 +/- 27 vs. 57 +/- 21 mL/min). At 12 months, patient and graft survival, incidence of biopsy-proven rejection and rates of steroid withdrawal were not statistically different (97% vs. 97%; 90% vs. 93%; 14.3% vs. 8.6% and 82.8% vs. 84.1%, respectively). Delayed and slow graft function (SGF) was not significantly different (18.6% vs. 12.3% and 11.4% vs. 13.7%, respectively). In patients who remained on treatment according to protocol at 12 months, eGFR was significantly higher with sirolimus (69 +/- 19 vs. 60 +/- 14 mL/min, p = 0.01). Overall study drug discontinuation rates were 28.2% with sirolimus and 14.9% with CsA. Adverse events (wound complications, mouth ulcers, diarrhea, hypokalemia, bronchopneumonia) and proteinuria >0.5 g/24h (38.8% vs. 5.6%, p < 0.001) were significantly more frequent in sirolimus-treated patients. Cytomegalovirus (CMV) infections were significantly less frequent with sirolimus (6% vs. 23%, p < 0.01). A CNI-free regimen using sirolimus-MMF can achieve excellent renal function, but patients on sirolimus experienced a high rate of adverse events and study drug discontinuation. PMID- 17868058 TI - 2509 living donor nephrectomies, morbidity and mortality, including the UK introduction of laparoscopic donor surgery. AB - The worldwide expansion of laparoscopic, at the expense of open, donor nephrectomy (DN) has been driven on the basis of faster convalescence for the donor. However, concerns have been expressed over the safety of the laparoscopic procedure. The UK Transplant National Registry collecting mandatory information on all living kidney donations in the country was analyzed for donations between November 2000 (start of living donor follow-up data reporting) to June 2006 to assess the safety of living DN, after the recent introduction of the laparoscopic procedure in the United Kingdom. Twenty-four transplant units reported data on 2509 donors (601 laparoscopic, 1800 open and 108 [4.3%] unspecified); 46.5% male; mean donor age: 46 years. There was one death 3 months postdischarge and a further five deaths beyond 1 year postdischarge. The mean length of stay was 1.5 days less for the laparoscopic procedure (p < 0.001). The risk of major morbidity for all donors was 4.9% (laparoscopic = 4.5%, open = 5.1%, p = 0.549). The overall rate of any morbidity was 14.3% (laparoscopic = 10.3%, open = 15.7%, p = 0.001). Living donation has remained a safe procedure in the UK during the learning curve of introduction of the laparoscopic procedure. The latter offers measurable advantages to the donor in terms of reduced length of stay and morbidity. PMID- 17868060 TI - Dissociation of depletional induction and posttransplant lymphoproliferative disease in kidney recipients treated with alemtuzumab. AB - Transplant patients are at the risk for posttransplant lymphoproliferative disease (PTLD), a virally-driven malignancy. Induction with the depleting antibody preparations Thymoglobulin and OKT3 is associated with PTLD suggesting that the T-cell depletion increases PTLD risk. We therefore studied 59 560 kidney recipients from the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database for a relationship between induction agent use and PTLD. Two agents with comparable T-cell depletional effects, alemtuzumab and Thymoglobulin, were compared to nondepletional induction agents or no induction. The overall incidence of PTLD was 0.46% and differed significantly by induction strategy (p < 0.01): without induction (0.43%), basiliximab (0.38%), daclizumab (0.33%), Thymoglobulin (0.67%) and alemtuzumab (0.37%). Thymoglobulin was associated with significantly increased PTLD risk (p = 0.0025), but alemtuzumab (p = 0.74), basiliximab (p = 0.33) and daclizumab, which trended toward a protective effect (p = 0.06), were not. Alemtuzumab and Thymoglobulin treated patients did not differ in any established parameter affecting PTLD risk although alemtuzumab is known to have a more pronounced B-cell depleting effect. Interestingly, maintenance therapy with an mTOR inhibitor was strongly associated with PTLD (0.71%, p < 0.0001). Thus, depletional induction is not an independent risk factor for PTLD. Rather, maintenance drug selection or perhaps the balance between B- and T-cell depletion may be more relevant determinants of PTLD risk. PMID- 17868061 TI - Cyclosporine abrogates de novo generation of Tregs independently of IL-2. PMID- 17868062 TI - Liver transplantation for familial amyloidotic polyneuropathy (FAP): a single center experience over 16 years. AB - Orthotopic liver transplantation (LTx) is currently the only available treatment that has been proven to halt the progress of familial amyloidotic polyneuropathy (FAP). The aim of this study was to assess mortality and symptomatic response to LTx for FAP. All 86 FAP patients transplanted at our hospital between April 1990 and November 2005 were included in the study. Five patients underwent retransplantation. The 1-, 3- and 5-year patient survival rates in patients transplanted during 1996-2005 were 94.6%, 92.3% and 92.3%, respectively, a significant difference from the rates of 76.7%, 66.7% and 66.7%, respectively, during 1990-1995 (p = 0.0003). Multivariate analysis revealed that the age at the time of LTx (>or=40 years), duration of the disease (>or=7 years) and modified body mass index (mBMI) (<600) were independent prognostic factors for patient survival. A halt in the progress of symptoms was noted in most patients, but only a minority experienced an improvement after LTx. To optimize the posttransplant prognosis, LTx should be performed in the early stages of the disease, and close post-LTx monitoring of heart function by echocardiography and of heart arrhythmia by Holter ECG is mandatory. PMID- 17868063 TI - Hyperlipidemia is associated with accelerated chronic kidney disease progression after lung transplantation. AB - Hyperlipidemia is associated with faster progression of chronic kidney disease (CKD) in the general public. We sought to investigate this association after lung transplantation. Data was retrospectively collected on 230 lung recipients transplanted between January 1997 and December 2003. Estimated glomerular filtration rates (eGFR) and lipid levels were recorded at regular intervals posttransplant. Independent associations between lipid levels early posttransplant and pertinent renal endpoints were investigated. Baseline LDL was 110 +/- 35 mg/dL and remained unchanged at 6 months. A faster decline in eGFR was seen in those with 6 month LDLs > versus < the mean level of 110 mg/dL (p = 0.05). By 6 months posttransplant eGFRs were lower in the 6 month LDL > versus < 110 mg/dL group (53 +/- 23 vs. 62 +/- 29 mL/min/1.73 m2, p = 0.01), a difference that persisted at 60 months (39 +/- 24 vs. 73 +/- 57 mL/min/1.73 m2, p = 0.05). On univariate analysis, a 6 month LDL in the highest quartile, i.e. >140 mg/dL, predicted faster progression to CKD, defined as declining to an eGFR < 30 mL/min/1.73 m2 (HR 1.5, p = 0.01). This finding persisted in the multivariate Cox proportional model (HR 1.4, p = 0.02). Hyperlipidemia predicts faster decline in renal function after lung transplant. Prospective trials are needed to confirm this finding. PMID- 17868064 TI - Diannexin, a novel annexin V homodimer, protects rat liver transplants against cold ischemia-reperfusion injury. AB - Ischemia/reperfusion injury (IRI) remains an important problem in clinical transplantation. Following ischemia, phosphatidylserine (PS) translocates to surfaces of endothelial cells (ECs) and promotes the early attachment of leukocytes/platelets, impairing microvascular blood flow. Diannexin, a 73 KD homodimer of human annexin V, binds to PS, prevents attachment of leukocytes/platelets to EC, and maintains sinusoidal blood flow. This study analyzes whether Diannexin treatment can prevent cold IRI in liver transplantation. Rat livers were stored at 4 degrees C in UW solution for 24 h, and then transplanted orthotopically (OLT) into syngeneic recipients. Diannexin (200 microg/kg) was infused into: (i) donor livers after recovering and before reperfusion, (ii) OLT recipients at reperfusion and day +2. Controls consisted of untreated OLTs. Both Diannexin regimens increased OLT survival from 40% to 100%, depressed sALT levels, and decreased hepatic histological injury. Diannexin treatment decreased TNF-alpha, IL-1beta, IP-10 expression, diminished expression of P-selectin, endothelial ICAM-1, and attenuated OLT infiltration by macrophages, CD4 cells and PMNs. Diannexin increased expression of HO-1/Bcl-2/Bcl xl, and reduced Caspase-3/TUNEL+ apoptotic cells. Thus, by modulating leukocyte/platelet trafficking and EC activation in OLTs, Diannexin suppressed vascular inflammatory responses and decreased apoptosis. Diannexin deserves further exploration as a novel agent to attenuate IRI, and thereby improve OLT function/increase organ donor pool. PMID- 17868065 TI - A retrospective analysis of immunosuppression compliance, dose reduction and discontinuation in kidney transplant recipients. AB - We describe factors associated with poor compliance and dose reductions and examine the relative impact of compliance, dose reduction and discontinuation on graft outcome. Medicare claims for MMF in 7062 deceased donor renal recipients with at least 1 year of graft function were used to calculate compliance and dose reductions. Compliance was modeled using medication possession ratio to define quartiles for poor, low, medium and high compliance. The relative impact of compliance, dose reduction and discontinuation on graft outcome was assessed with Cox proportional hazards. Pediatric (Age 0-18, Odds ratio = 1.71, 95% CI 1.11 2.63, p = 0.014) and adolescent recipients (19-24, 1.57, 1.23-2.00, p < 0.001) were more likely poorly compliant compared to adults age 25-44. Poor compliance was also associated with physical limitations, hypertension, delayed graft function, rejection, infection and GI conditions. Poor (1.43, 1.11-1.84, p = 0.005) and low (1.46, 1.13-1.88, p = 0.004) compliance was associated with an increased hazard of graft loss as was >50% dose reduction (1.69, 1.15-2.50, p = 0.008) and discontinuation (8.34, 6.85-10.2, p < 0.001). Medication possession ratios lower than the 3-year mean were associated with an increased risk of graft loss. These results may indicate that interventions to improve compliance among kidney transplant recipients should strive for high rather than discourage low compliance. PMID- 17868066 TI - Liver transplantation for hepatocellular carcinoma: validation of the UCSF expanded criteria based on preoperative imaging. AB - We previously suggested that in patients with heptocellular carcinoma (HCC), the conventional Milan criteria (T1/T2) for orthotopic liver transplantation (OLT) could be modestly expanded based on pathology (UCSF criteria). The present study was undertaken to prospectively validate the UCSF criteria based on pretransplant imaging. Over a 5-year period, the UCSF criteria were used as selection guidelines for OLT in 168 patients, including 38 patients exceeding Milan but meeting UCSF criteria (T3A). The 1- and 5-year recurrence-free probabilities were 95.9% and 90.9%, and the respective survivals without recurrence were 92.1% and 80.7%. Patients with preoperative T1/T2 HCC had 1- and 5-year recurrence-free probabilities of 95.7% and 90.1%, respectively, versus 96.9% and 93.6%, respectively, for preoperative T3A stage (p = 0.58). Under-staging was observed in 20% of T2 and 29% of T3A HCC (p = 0.26). When explant tumor exceeded UCSF criteria (15%), the 1- and 5-year recurrence-free probabilities were 80.4% and 59.5%, versus 98.6% and 96.7%, respectively, for those within UCSF criteria (p < 0.0001). In conclusion, our results validated the ability of the UCSF criteria to discriminate prognosis after OLT and to serve as selection criteria for OLT, with a similar risk of tumor recurrence and under-staging when compared to the Milan criteria. PMID- 17868067 TI - Bloodstream infections among transplant recipients: results of a nationwide surveillance in Spain. AB - Bloodstream infections (BSIs) are a major cause of morbidity and mortality in transplant recipients. The aim of this study is to describe the incidence, microbiology and outcomes of BSIs in transplant recipients in Spain. The Spanish Network for Research on Infection in Transplantation (RESITRA) is formed by 16 centers with transplant program in Spain. The incidence and characteristics of BSIs in transplant patients were obtained prospectively from the cohort. We included 3926 transplant recipients (2935 solid organ and 991 hematopoietic stem cell transplants). Overall, 730 episodes of BSIs were recorded with an incidence rate ranging from 3 episodes per 10 000 transplant days in kidney recipients to 44 episodes per 10 000 transplant days in allogeneic hematopoietic stem cell transplantation (HSCT). The most frequent sources were intravascular catheters and the most frequent microorganisms isolated were coagulase-negative staphylococci. Crude mortality of BSIs was 7.8%, being highest in liver recipients (16%). Multidrug resistant nonfermentative gram-negative BSIs had significantly worse prognosis than those caused by their susceptible counterparts (p = 0.015), but no differences were found between resistant and susceptible gram negative enteric bacilli, S. aureus or Candida spp. BSIs are still a major concern in transplant recipients. The increasing isolations of multiresistant microorganisms represent a challenge for the next years. PMID- 17868068 TI - Therapeutic monitoring of mycophenolic acid: is there clinical utility? PMID- 17868069 TI - Medication errors: an important component of nonadherence to medication in an outpatient population of lung transplant recipients. AB - Data about medication errors in outpatients are limited. Medication errors, defined as discordance between the most recent flow-sheet version, the patient's diary card or the contents of the pill container were assessed systematically after announcement in an outpatient setting of lung transplant recipients by a direct observation approach. A total of 101 patients took a median of 15 (13-17) different drugs and 31 (26-38) pills daily. A total of 2253 doses of drugs were further analyzed. A total of 152 errors were identified resulting in 303 incorrect doses. Lack of keeping a diary card was the only factor significantly associated with a higher rate of incorrect doses (regression coefficient 0.24, p = 0.02). Furthermore, a significant correlation of medication errors with clinical adverse events could be demonstrated. This study shows that medication errors are frequent in a population which has to comply with a complex drug regimen. The need for error control as a basic requirement for drug adherence must be accentuated. Mostly, medication errors seem to occur system-based. Therefore, redundant error control mechanisms and alertness of both the patient and the care-giver should be initiated systematically. PMID- 17868070 TI - Role of IFNgamma in allograft tolerance mediated by CD4+CD25+ regulatory T cells by induction of IDO in endothelial cells. AB - Regulatory T cells have been described to specifically accumulate at the site of regulation together with effector T cells and antigen-presenting cells, establishing a state of local immune privilege. However the mechanisms of this interplay remain to be defined. We previously demonstrated, in a fully MHC mismatched rat cardiac allograft combination, that a short-term treatment with a deoxyspergualine analogue, LF15-0195, induces long-term allograft tolerance with a specific expansion of regulatory CD4+CD25+T cells that accumulate within the graft. In this study, we show that following transfer of regulatory CD4+T cells to a secondary irradiated recipient, regulatory CD25+Foxp3+ and CD25+Foxp3(-) CD4+T cells accumulate at the graft site and induce graft endothelial cell expression of Indoleamine 2, 3-dioxygenase (IDO) by an IFNgamma-dependent mechanism. Moreover, in vivo transfer of tolerance can be abrogated by blocking IFNgamma or IDO, and anti-IFNgamma reduces the survival/expansion of alloantigen induced regulatory Foxp3+CD4+T cells. Together, our results demonstrate interrelated mechanisms between regulatory CD4+CD25+T cells and the graft endothelial cells in this local immune privilege, and a key role for IFNgamma and IDO in this process. PMID- 17868071 TI - Synergistic deposition of C4d by complement-activating and non-activating antibodies in cardiac transplants. AB - The role of non-complement-activating alloantibodies in humoral graft rejection is unclear. We hypothesized that the non-complement-activating alloantibodies synergistically activate complement in combination with complement-activating antibodies. B10.A hearts were transplanted into immunoglobulin knock out (Ig-KO) mice reconstituted with monoclonal antibodies to MHC class I antigens. In allografts of unreconstituted Ig-KO recipients, no C4d was detected. Similarly, reconstitution with IgG1 or low dose IgG2b alloantibodies did not induce C4d deposition. However, mice administered with a low dose of IgG2b combined with IgG1 had heavy linear deposits of C4d on vascular endothelium. C4d deposits correlated with decreased graft survival. To replicate this synergy in vitro, mononuclear cells from B10.A mice were incubated with antibodies to MHC class I antigens followed by incubation in normal mouse serum. Flow cytometry revealed that both IgG2a and IgG2b synergized with IgG1 to deposit C4d. This synergy was significantly decreased in mouse serum deficient in mannose binding lectin (MBL) and in serum deficient in C1q. Reconstitution of MBL-A/C knock out (MBL-KO) serum with C1q-knock out (C1q-KO) serum reestablished the synergistic activity. This suggests a novel role for non-complement-activating alloantibodies and MBL in humoral rejection. PMID- 17868072 TI - ICAM-1 peptide inhibitors of T-cell adhesion bind to the allosteric site of LFA 1. An NMR characterization. AB - We have used nuclear magnetic resonance to characterize the binding site of two intercellular adhesion molecule-1 derived cyclic peptides, cIBC and cIBR, to the I-domain of leukocyte function-associated antigen-1. These peptides inhibit the leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction known to play a key role in autoimmune diseases and cancer metastasis. Perturbation of the chemical shifts and intensities of the nuclear magnetic resonance signals corresponding to a number of residues of the I-domain of leukocyte function-associated antigen-1 show that both peptides bind to the I domain allosteric site, the binding site of I-domain allosteric inhibitors such as lovastatin, and therefore the peptides probably also act as allosteric inhibitors of leukocyte function-associated antigen-1. Molecular models of the interaction of these two cyclic peptides with leukocyte function-associated antigen-1 I-domain show that the binding mode of the three molecules are analogous: the hydrophobic residues of the peptides remain buried and occupy the same positions as the apolar groups of lovastatin, while the peptides regions containing the most polar residues are flexible and primarily exposed to the solvent. These results suggest an allosteric mechanism for the inhibitory effect on T-cell adhesion displayed by both peptides, which exhibit potential as therapeutic agents. PMID- 17868073 TI - Synthesis and evaluation of dual wavelength fluorescent benzo[b]thiophene boronic acid derivatives for sugar sensing. AB - Cell surface glycoproteins have been known to play very important roles in various physiologic and pathologic processes. Small molecule compounds capable of carbohydrate recognition can be very useful for the development of sensing, diagnostic, and therapeutic agents. Along this line, we are interested in developing water-soluble fluorescent boronic acid compounds for carbohydrate recognition. As such, a series of benzo[b]thiophene boronic acid derivatives have been synthesized and their fluorescent properties analyzed at physiologic pH. Benzo[b]thiophene derivatives were found to be a new type of fluorescent reporter compounds capable of dual fluorescent emission under physiologic pH conditions. Compounds 1, 3, 4, 5, and 6 showed unusual emission wavelength shifts upon binding of sugars. These boronic acids will be useful tools for building glycoprotein biosensors for biologic applications. PMID- 17868074 TI - Reassessing the role of phosphocaveolin-1 in cell adhesion and migration. AB - Although phosphorylation on tyrosine 14 was identified early in the discovery of caveolin-1, the functional significance of this modification still remains elusive. Recent evidence points to a role of caveolin-1 tyrosine 14 phosphorylation in cell adhesion and migration. These results are based on a variety of tools, including a widely used mouse monoclonal anti-phosphocaveolin-1 antibody, which labels, in cultured cells, a protein localized at or near focal adhesions. We here report results from three independent laboratories, showing that this antibody recognizes phosphocaveolin-1 amongst other proteins in immunoblot analyses and that the signal obtained with this antibody in immunostaining experiments is in part due to labeling of paxillin. Published data need to be interpreted keeping in mind that images of phosphocaveolin-1 cellular localization obtained using this antibody are not valid. We re-evaluate the current knowledge about the role of caveolin-1 in cell adhesion and migration in view of this new information. PMID- 17868075 TI - EHD1 interacts with retromer to stabilize SNX1 tubules and facilitate endosome-to Golgi retrieval. AB - Endosome-to-Golgi retrieval of the cation-independent mannose 6-phosphate receptor (CIMPR) requires the function of the retromer complex. Retromer is localized to endosomes and comprises two distinct sub complexes: the vacuolar protein sorting 35/29/26 sub complex that binds cargo and the sorting nexin (SNX)1/2 sub complex that tubulates endosomal membranes. To identify up- or down stream regulatory factors of retromer, a comparative proteomic strategy was employed. Protein profiles of endosomally enriched membranes, from either wild type or retromer-deficient mouse cells, were compared to identify proteins with either elevated or reduced expression levels. Eps15 homology domain-containing protein-1 (EHD1) was identified in endosomally enriched membrane fractions from retromer-deficient cells and was found to be approximately threefold upregulated in the absence of retromer. EHD1 is localized to tubular and vesicular endosomes, partially colocalizes with retromer and is associated with retromer in vivo. Mutation of the nucleotide-binding P-loop of EHD1 results in a dominant-negative effect upon retromer localization and endosome-to-Golgi retrieval, while loss of EHD1 expression by RNA interference destabilizes SNX1-positive tubules and inhibits endosome-to-Golgi retrieval. The interaction between EHD1 and retromer and the requirement for EHD1 to stabilize SNX1-tubules establish EHD1 as a novel facilitating component of endosome-to-Golgi retrieval. PMID- 17868076 TI - Shortage of quantitative geneticists in animal breeding. PMID- 17868077 TI - Fine mapping of a quantitative trait locus on chromosome 9 affecting non-return rate in Swedish dairy cattle. AB - We previously mapped a quantitative trait locus (QTL) affecting the trait non return rate at 56 days in heifers to bovine chromosome 9. The purpose of this study was to confirm and refine the position of the QTL by using a denser marker map and fine mapping methods. Five families that previously showed segregation for the QTL were included in the study. The mapping population consisted of 139 bulls in a granddaughter design. All bulls were genotyped for 25 microsatellite markers surrounding the QTL on chromosome 9. We also analysed the correlated trait number of inseminations per service period in heifers. Both traits describe the heifer's ability to become pregnant after insemination. Linkage analysis, linkage disequilibrium and combined linkage and linkage disequilibrium analysis were used to analyse the data. Analysis of the families jointly by linkage analysis resulted in a significant but broad QTL peak for non-return rate. Results from the combined analysis gave a sharp QTL peak with a well-defined maximum in between markers BMS1724 and BM7209, at the same position as where the highest peak from the linkage disequilibrium analysis was found. One of the sire families segregated clearly at this position and the difference in effects between the two sire haplotypes was 2.9 percentage units in non-return rate. No significant results were found for the number of inseminations in the combined analysis. PMID- 17868078 TI - Distribution of nuclear mitochondrial DNA in cattle nuclear genome. AB - The nuclear mitochondrial pseudogenes (numts), originated from mtDNA insertions into the nuclear genome, have been detected to exist in many species. However, the distribution of numts in cattle nuclear genome yet has not been fully reported. By referring to the whole cattle mtDNA sequence and to the recently released cattle nuclear genome by Human Genome Sequencing Center (HGSC), 303 numts were identified by BLAST with 55 numts unmapped to cattle nuclear genome. Further analysis found that the size of the numts ranges from 37 to 1932 bp, and the homologous identity between numts and their corresponding mtDNA fragments varies from 73 to 98%. Furthermore, the identified cattle numts cover nearly all the mitochondrial genes including mtDNA control region, distributing over all the chromosomes with the exception of the chromosome 23 and Y chromosome (in the latter the sequence data are not available). In the discovered numts, 29 relatively complete mitochondrial genes, which were distributed in 72 numts, were detected. Undoubtedly, this research would provide some valuable information for successive research related to mitochondrial genes and the evolution of cattle. PMID- 17868079 TI - Analysis and mapping of CACNB4, CHRNA1, KCNJ3, SCN2A and SPG4, physiological candidate genes for porcine congenital progressive ataxia and spastic paresis. AB - The cause of porcine congenital progressive ataxia and spastic paresis (CPA) is unknown. This severe neuropathy manifests shortly after birth and is lethal. The disease is inherited as a single autosomal recessive allele, designated cpa. In a previous study, we demonstrated close linkage of cpa to microsatellite SW902 on porcine chromosome 3 (SSC3), which corresponds syntenically to human chromosome 2. This latter chromosome contains ion channel genes (Ca(2+), K(+) and Na(+)), a cholinergic receptor gene and the spastin (SPG4) gene, which cause human epilepsy and ataxia when mutated. We mapped porcine CACNB4, KCNJ3, SCN2A and CHRNA1 to SSC15 and SPG4 to SSC3 with the INRA-Minnesota porcine radiation hybrid panel (IMpRH) and we sequenced the entire open reading frames of CACNB4 and SPG4 without finding any differences between healthy and affected piglets. An anti epileptic drug treatment with ethosuximide did not change the severity of the disease, and pigs with CPA did not exhibit the corticospinal tract axonal degeneration found in humans suffering from hereditary spastic paraplegia, which is associated with mutations in SPG4. For all these reasons, the hypothesis that CACNB4, CHRNA1, KCNJ3, SCN2A or SPG4 are identical with the CPA gene was rejected. PMID- 17868080 TI - Genetic correlations between body condition scores and fertility in dairy cattle using bivariate random regression models. AB - Genetic correlations between body condition score (BCS) and fertility traits in dairy cattle were estimated using bivariate random regression models. BCS was recorded by the Swiss Holstein Association on 22,075 lactating heifers (primiparous cows) from 856 sires. Fertility data during first lactation were extracted for 40,736 cows. The fertility traits were days to first service (DFS), days between first and last insemination (DFLI), calving interval (CI), number of services per conception (NSPC) and conception rate to first insemination (CRFI). A bivariate model was used to estimate genetic correlations between BCS as a longitudinal trait by random regression components, and daughter's fertility at the sire level as a single lactation measurement. Heritability of BCS was 0.17, and heritabilities for fertility traits were low (0.01-0.08). Genetic correlations between BCS and fertility over the lactation varied from: -0.45 to 0.14 for DFS; -0.75 to 0.03 for DFLI; from -0.59 to -0.02 for CI; from -0.47 to 0.33 for NSPC and from 0.08 to 0.82 for CRFI. These results show (genetic) interactions between fat reserves and reproduction along the lactation trajectory of modern dairy cows, which can be useful in genetic selection as well as in management. Maximum genetic gain in fertility from indirect selection on BCS should be based on measurements taken in mid lactation when the genetic variance for BCS is largest, and the genetic correlations between BCS and fertility is strongest. PMID- 17868081 TI - Multi-breed genetic evaluation in a Gelbvieh population. AB - A multi-breed model was presented for the genetic evaluation of growth traits in beef cattle. In addition to the fixed effects, random direct and maternal genetic effects, and random maternal permanent environmental effects are considered; the model also fits direct and maternal heterosis and direct and maternal breed-of founder (BOF) x generation group effects using a Bayesian approach that weights prior literature estimates relative to information supplied by the dataset to which the model will be applied. The multi-breed evaluation procedures also allow the inclusion of external evaluations for animals of other breeds. The multi breed model was applied to a dataset provided by the American Gelbvieh Association. Different analyses were conducted by varying the weights given to the prior literature relative to the information provided by the dataset. Large differences were observed for the heterosis estimates, the BOF x generation group effect estimates, and the predicted breeding values across breeds due to the weights posed on prior literature estimates versus estimates derived directly from data. However, the rankings within breed were observed to be relatively robust to the different weights on prior information. PMID- 17868082 TI - Estimates of genetic parameters for growth traits in Kermani sheep. AB - Birth weight (BW), weaning weight (WW), 6-month weight (W6), 9-month weight (W9) and yearling weight (YW) of Kermani lambs were used to estimate genetic parameters. The data were collected from Shahrbabak Sheep Breeding Research Station in Iran during the period of 1993-1998. The fixed effects in the model were lambing year, sex, type of birth and age of dam. Number of days between birth date and the date of obtaining measurement of each record was used as a covariate. Estimates of (co)variance components and genetic parameters were obtained by restricted maximum likelihood, using single and two-trait animal models. Based on the most appropriate fitted model, direct and maternal heritabilities of BW, WW, W6, W9 and YW were estimated to be 0.10 +/- 0.06 and 0.27 +/- 0.04, 0.22 +/- 0.09 and 0.19 +/- 0.05, 0.09 +/- 0.06 and 0.25 +/- 0.04, 0.13 +/- 0.08 and 0.18 +/- 0.05, and 0.14 +/- 0.08 and 0.14 +/- 0.06 respectively. Direct and maternal genetic correlations between the lamb weights varied between 0.66 and 0.99, and 0.11 and 0.99. The results showed that the maternal influence on lamb weights decreased with age at measurement. Ignoring maternal effects in the model caused overestimation of direct heritability. Maternal effects are significant sources of variation for growth traits and ignoring maternal effects in the model would cause inaccurate genetic evaluation of lambs. PMID- 17868083 TI - Genetic parameters for the prevalence of osteochondrosis in the limb joints of South German Coldblood horses. AB - Heritabilities were estimated for osteochondrosis (OC) in fetlock and hock joints and palmar/plantar osseous fragments in fetlock joints of South German Coldblood (SGC) horses using Residual Maximum Likelihood (REML) under a linear animal model. The analyses were based on the results of a standardized radiographic examination of 167 SGC horses with a mean age of 14 months. The heritabilities linearly estimated and transformed onto the liability scale were for OC in fetlock joints 0.16 and for OC in hock joints 0.04. Considering fetlock and hock OC together, results in a heritability of 0.17. Palmar/plantar osseus fragments of the fetlock joints showed a heritability of 0.48. We concluded that there is most likely a genetic component in the variation of the development of osteochondrosis in fetlock and hock joints as well as for palmar/plantar osseus fragments of fetlock joints of the investigated population of SGC horses. PMID- 17868084 TI - Estimation of genetic parameters and prediction of breeding values for multivariate threshold and continuous data in a simulated horse population using Gibbs sampling and residual maximum likelihood. AB - Simulated horse data were used to compare multivariate estimation of genetic parameters and prediction of breeding values (BV) for categorical, continuous and molecular genetic data using linear animal models via residual maximum likelihood (REML) and best linear unbiased prediction (BLUP) and mixed linear-threshold animal models via Gibbs sampling (GS). Simulation included additive genetic values, residuals and fixed effects for one continuous trait, liabilities of four binary traits, and quantitative trait locus (QTL) effects and genetic markers with different recombination rates and polymorphism information content for one of the liabilities. Analysed data sets differed in the number of animals with trait records and availability of genetic marker information. Consideration of genetic marker information in the model resulted in marked overestimation of the heritability of the QTL trait. If information on 10,000 or 5,000 animals was used, bias of heritabilities and additive genetic correlations was mostly smaller, correlation between true and predicted BV was always higher and identification of genetically superior and inferior animals was - with regard to the moderately heritable traits, in many cases - more reliable with GS than with REML/BLUP. If information on only 1,000 animals was used, neither GS nor REML/BLUP produced genetic parameter estimates with relative bias 50% for all traits. Selection decisions for binary traits should rather be based on GS than on REML/BLUP breeding values. PMID- 17868085 TI - Automated analysis of neurite branching in cultured cortical neurons using HCA Vision. AB - Manual neuron tracing is a very labor-intensive task. In the drug screening context, the sheer number of images to process means that this approach is unrealistic. Moreover, the lack of reproducibility, objectivity, and auditing capability of manual tracing is limiting even in the context of smaller studies. We have developed fast, sensitive, and reliable algorithms for the purpose of detecting and analyzing neurites in cell cultures, and we have integrated them in software called HCA-Vision, suitable for the research environment. We validate the software on images of cortical neurons by comparing results obtained using HCA-Vision with those obtained using an established semi-automated tracing solution (NeuronJ). The effect of the Sez-6 deletion was characterized in detail. Sez-6 null neurons exhibited a significant increase in neurite branching, although the neurite field area was unchanged due to a reduction in mean branch length. HCA-Vision delivered considerable speed benefits and reliable traces. PMID- 17868086 TI - Practical time-gated luminescence flow cytometry. II: experimental evaluation using UV LED excitation. AB - In the previous article [Part 1 (8)], we have modelled alternative approaches to design of practical time-gated luminescence (TGL) flow cytometry and examined the feasibility of employing a UV LED as the excitation source for the gated detection of europium dye labelled target in rapid flow stream. The continuous flow-section approach is well suited for rare-event cell counting in applications with a large number of nontarget autofluorescent particles. This article presents details of construction, operation and evaluation of a TGL flow cytometer using a UV LED excitation and a gated high-gain channel photomultiplier tube (CPMT) for detection. The compact prototype TGL flow cytometer was constructed and optimised to operate at a TGL cycle rate of 6 kHz, with each cycle consisting of 100 micros LED pulsed excitation and approximately 60 micros delay-gated detection. The performance of the TGL flow cytometer was evaluated by enumerating 5.7 microm Eu(3+) luminescence beads (having comparable intensity to europium-chelate labeled Giardia cysts) in both autofluorescence-rich environmental water concentrates and Sulforhodamine 101 (S101) solutions (broadband red fluorescence covering the spectral band of target signals), respectively. The prototype TGL flow cytometer was able to distinguish the target beads, and a maximum signal to background ratio of 38:1 was observed. Neither the environmental water concentrates nor S101 solution contributed to the background in the TGL detection phase. The counting efficiency of the TGL flow cytometer was typically >93% of values determined using conventional counting methods. PMID- 17868087 TI - Practical time-gated luminescence flow cytometry. I: concepts. AB - The method of time-gated detection of long-lifetime (1-2,000 micros) luminescence labeled microorganisms following rapid excitation pulses has proved highly efficient in suppressing nontarget autofluorescence (<0.1 micros), scatterings, and other prompt stray light (Hemmila and Mukkala, Crit Rev Clin Lab Sci 2001;38:441-519). The application of such techniques to flow cytometry is highly attractive but there are significant challenges in implementing pulsed operation mode to rapid continuous flowing sample to achieve high cell analysis rates (Leif R, Vallarino L, Rare-earth chelates as fluorescent markers in cell separation and analysis, In: Cell Separation Science and Technology, ACS Symposium Series 464, American Chemical Society, 1991, pp 41-58; Condrau et al., Cytometry 1994;16:187 194; Condrau et al., Cytometry 1994;16:195-205; Shapiro HM, Improving signals from labels: Amplification and other techniques, In: Practical Flow Cytometry, 4th ed., Wiley, New York, 2002, p 345). We present here practical approaches for achieving high cell analysis rates at 100% detection efficiency, using time-gated luminescence (TGL) flow cytometry. In particular, we report that new-generation UV LEDs are practical sources in TGL flow cytometry. Spatial effects of long lived luminescence from the target fluorophore in a fast-flowing sample stream have been investigated; excitation and detection requirements in TGL flow cytometry were theoretically analyzed; two practical approaches, a triggered model and a continuous flow-section model, were considered as a function of flow speed, sizes and relative positions of the excitation/detection spots, label lifetime, excitation pulse duration/intensity, and detection duration. A particular configuration using LED excitation to detect europium dye-labeled targets in such a system has been modeled in detail. In the triggered model, TGL mode is confined to a low repetition rate (<1 kHz) and engaged only while a target particle is present in the excitation zone. In the flow-section model, TGL mode is engaged continuously at high repetition rates to permit much higher cell arrival rates. The detection of 5.7-microm europium calibration beads in a UV LED excited TGL flow cytometer has been shown to be feasible with a calculated signal to-background ratio up to 11:1. PMID- 17868088 TI - Generation of a Twist1 conditional null allele in the mouse. AB - Twist1 is the mouse ortholog of TWIST1, the human gene mutated in Saethre-Chotzen syndrome. Previously, a Twist1 null allele was generated by gene targeting in mouse embryonic stem cells. Twist1 heterozygous mice develop polydactyly and a craniofacial phenotype similar to Saethre-Chotzen patients. Mice homozygous for the Twist1 null allele die around embryonic day 11.5 (E11.5) with cranial neural tube closure and vascular defects, hindering in vivo studies of Twist1 function at later stages of development. Here, we report the generation of a Twist1 conditional null allele in mice that functions like a wild-type allele but can be converted to a null allele upon Cre-mediated recombination. PMID- 17868089 TI - Floxed allele for conditional inactivation of the voltage-gated sodium channel beta1 subunit Scn1b. AB - The voltage-gated sodium channel gene Scn1b encodes the auxiliary subunit beta1, which is widely distributed in neurons and glia of the central and peripheral nervous systems, cardiac myocytes, skeletal muscle myocytes, and neuroendocrine cells. We showed previously that the Scn1b null mutation results in a complex and severe phenotype that includes retarded growth, seizures, ataxia, and death by postnatal day 21. We generated a floxed allele of Scn1b by inserting loxP sites surrounding the second coding exon. Ubiquitous deletion of the floxed exon by Cre recombinase using CMV-Cre-transgenic mice produced the Scn1b(del) allele. The null phenotype of Scn1b(del) homozygotes is indistinguishable from that of Scn1b nulls and confirms the invivo inactivation of Scn1b. Conditional inactivation ofthe floxed allele will make it possible to circumvent the lethality that results from complete loss of this gene, such that the physiological role of Scn1b in specific cell types and/or specific developmental time points can be investigated. PMID- 17868090 TI - Cyclin degradation for cancer therapy and chemoprevention. AB - Cancer is characterized by uncontrolled cell division resulting from multiple mutagenic events. Cancer chemoprevention strategies aim to inhibit or reverse these events using natural or synthetic pharmacologic agents. Ideally, this restores normal growth control mechanisms. Diverse classes of compounds have been identified with chemopreventive activity. What unites many of them is an ability to inhibit the cell cycle by specifically modulating key components. This delays division long enough for cells to respond to mutagenic damage. In some cases, damage is repaired and in others cellular damage is sufficient to trigger apoptosis. It is now known that pathways responsible for targeting G1 cyclins for proteasomal degradation can be engaged pharmacologically. Emergence of induced cyclin degradation as a target for cancer therapy and chemoprevention in pre clinical models is discussed in this article. Evidence for cyclin D1 as a molecular pharmacologic target and biological marker for clinical response is based on experience of proof of principle trials. PMID- 17868091 TI - Generation of an Frs2alpha conditional null allele. AB - The fibroblast growth factor (FGF) signaling family controls a broad spectrum of cellular processes in development and adult tissue homeostasis and function, which is expressed in almost all tissues at all stages. FGF receptor substrate 2 alpha (FRS2alpha) is an adaptor protein that recruits downstream substrates to the FGF receptor (FGFR) tyrosine kinase. Disruption of Frs2alpha gene in mice abrogates activation of the mitogen-activated protein kinase pathway by the FGFR and leads to embryonic lethality at day E7.5 post copulation. To circumvent the embryonic lethality resulting from disruption of the Frs2alpha gene, which hinders further characterization of the role of FRS2alpha in adult tissue function and homeostasis, we generated an Frs2alpha conditional null allele for temporally- and tissue-specific disruption of the Frs2alpha gene. Using gene targeting in mouse embryonic stem cells, we introduced two loxP sites flanking the largest coding exon, exon 5, in the Frs2alpha allele. Our results indicate that the floxed Frs2alpha (Frs2alpha(flox)) allele is a true conditional null allele that encodes wildtype activity and is converted to a null allele after Cre recombinase mediated recombination. PMID- 17868092 TI - Back to the future: ribonuclease A. AB - Pancreatic ribonuclease A (EC 3.1.27.5, RNase) is, perhaps, the best-studied enzyme of the 20th century. It was isolated by Rene Dubos, crystallized by Moses Kunitz, sequenced by Stanford Moore and William Stein, and synthesized in the laboratory of Bruce Merrifield, all at the Rockefeller Institute/University. It has proven to be an excellent model system for many different types of experiments, both as an enzyme and as a well-characterized protein for biophysical studies. Of major significance was the demonstration by Chris Anfinsen at NIH that the primary sequence of RNase encoded the three-dimensional structure of the enzyme. Many other prominent protein chemists/enzymologists have utilized RNase as a dominant theme in their research. In this review, the history of RNase and its offspring, RNase S (S-protein/S-peptide), will be considered, especially the work in the Merrifield group, as a preface to preliminary data and proposed experiments addressing topics of current interest. These include entropy enthalpy compensation, entropy of ligand binding, the impact of protein modification on thermal stability, and the role of protein dynamics in enzyme action. In continuing to use RNase as a prototypical enzyme, we stand on the shoulders of the giants of protein chemistry to survey the future. PMID- 17868093 TI - Activity of short segments of Type I antifreeze protein. AB - In this work, we present a study on the antifreeze activity of short segments of a Type I antifreeze protein, instead of the whole protein. This approach simplifies the correlation between antifreeze protein characteristics, such as hydrophilicity/hydrophobicity, and the effect of these characteristics on the antifreeze mechanism. Three short polypeptides of Type I AFP have been synthesized. Their antifreeze activity and interactions with water and ice crystals have been analyzed by various techniques such as circular dichroism spectroscopy, X-ray diffraction, differential scanning calorimetry, and osmometry. It is shown that one short segment of Type I AFP has an antifreeze activity of about 60% of the native protein activity. In this work, we demonstrate that short segments of Type I AFPs possess nonzero thermal hysteresis and result in modifications in the growth habits and growth rates of ice. This approach enables the preparation of large quantities of short AFP segments at low cost with high antifreeze activity, and opens the possibility of developing the commercial potential of AFPs. PMID- 17868094 TI - Conformational consequences of protein glycosylation: preparation of O-mannosyl serine and threonine building blocks, and their incorporation into glycopeptide sequences derived from alpha-dystroglycan. AB - With the goal to investigate the structural impact of O-mannosyl glycosylation on alpha-dystroglycan, a glycoprotein that has an important role in the extracellular organization of muscle, glycopeptides derived from its mucin-like sequence have been prepared by solid-phase peptide synthesis. Two approaches have been explored to obtain needed mannosylated serine and threonine building blocks. With the alpha-carboxyl group unprotected, and with tetraaceto-1-fluoro-alpha-D mannose as the sugar donor, the desired alpha-O-mannosyl-Fmoc-Ser/Thr formed, along with mannosyl ester isomers and the species with mannose attached to both hydroxyl and carboxyl functions. Relevant mechanistic questions and stability issues were elucidated. Alternatively, building blocks were made with the alpha carboxyl protected/activated as the pentafluorophenyl (Pfp) ester. Glycopeptides synthesized herein contained 5-9 residues, and featured one, two, and four consecutive Ser and/or Thr residues O-glycosylated with mannose. Circular dichroism (CD) spectra for Man-containing glycopeptides recorded in water show them to be not well ordered. For one of the alpha-dystroglycan-derived sequences, the comparative conformational consequences of glycosylation by either Man or GalNAc have been examined by CD and NMR, with both methods showing a more organized structure when GalNAc is present. PMID- 17868095 TI - Importance of RNA-protein interactions in bacterial ribonuclease P structure and catalysis. AB - Ribonuclease P (RNase P) is a ribonucleoprotein (RNP) complex that catalyzes the metal-dependent maturation of the 5' end of precursor tRNAs (pre-tRNAs) in all organisms. RNase P is comprised of a catalytic RNA (P RNA), and at least one essential protein (P protein). Although P RNA is the catalytic subunit of the enzyme and is active in the absence of P protein under high salt concentrations in vitro, the protein is still required for enzyme activity in vivo. Therefore, the function of the P protein and how it interacts with both P RNA and pre-tRNA have been the focus of much ongoing research. RNA-protein interactions in RNase P serve a number of critical roles in the RNP including stabilizing the structure, and enhancing the affinity for substrates and metal ions. This review examines the role of RNA-protein interactions in bacterial RNase P from both structural and mechanistic perspectives. PMID- 17868096 TI - A global double-fluorescent Cre reporter mouse. AB - The Cre/loxP system has been used extensively for conditional mutagenesis in mice. Reporters of Cre activity are important for defining the spatial and temporal extent of Cre-mediated recombination. Here we describe mT/mG, a double fluorescent Cre reporter mouse that expresses membrane-targeted tandem dimer Tomato (mT) prior to Cre-mediated excision and membrane-targeted green fluorescent protein (mG) after excision. We show that reporter expression is nearly ubiquitous, allowing visualization of fluorescent markers in live and fixed samples of all tissues examined. We further demonstrate that mG labeling is Cre-dependent, complementary to mT at single cell resolution, and distinguishable by fluorescence-activated cell sorting. Both membrane-targeted markers outline cell morphology, highlight membrane structures, and permit visualization of fine cellular processes. In addition to serving as a global Cre reporter, the mT/mG mouse may also be used as a tool for lineage tracing, transplantation studies, and analysis of cell morphology in vivo. PMID- 17868097 TI - Coefficients of friction, lubricin, and cartilage damage in the anterior cruciate ligament-deficient guinea pig knee. AB - The coefficient of friction (COF) of articular cartilage is thought to increase with osteoarthritis (OA) progression, and this increase may occur due to a decrease in lubricin concentration. The objectives of this study were to measure the COF of guinea pig tibiofemoral joints with different stages of OA and to establish relationships between COF, lubricin concentrations in synovial fluid, and degradation status using the Hartley guinea pig model. Both hind limbs from 24 animals were harvested: seven 3-month-old (no OA), seven 12-month-old (mild OA), and 10 that were euthanized at 12 months of age after undergoing unilateral ACL transection at 3 months of age (moderate OA). Contralateral knees served as age-matched controls. COFs of the tibiofemoral joints were measured using a pendulum apparatus. Synovial fluid lavages were analyzed to determine the concentration and integrity of lubricin using ELISA and Western blot, and the overall articular cartilage status was evaluated by histology. The results showed that the mean COF in the ACL-deficient knees was significantly greater than that of the no OA (p < 0.01) and mild OA knees (p < 0.01). Lubricin concentrations in the ACL-deficient knees were significantly lower than that in both of the other groups (p < 0.01). No significant differences in COF or lubricin concentration were found between the no OA and mild OA knees. Histology verified the extent of cartilage damage in each group. PMID- 17868099 TI - Quality of life in epilepsy, multiple sclerosis, and beyond. PMID- 17868100 TI - Efficacy of early treatment of facial port wine stains in newborns: a review of 49 cases. AB - BACKGROUND: Port wine stains (PWS) affect 0.3-0.5% of both sexes of newborns, usually occurring on the face. OBJECTIVE: To document safety and effectiveness of cryogen spray cooled, pulsed-dye laser at higher fluences than previously used to lighten facial PWS in infants < or =6 months, and establish that frequent treatment early in life yields better clearance than if delayed until later in life. MATERIALS AND METHODS: Forty-nine infants who had been treated with pulsed dye laser treatments for facial PWS at < or =6 months were identified by case review of photographs, age, sex, PWS severity score prior to laser treatment, number of treatments, and improvement following laser therapy. RESULTS: Patients averaged 9.3 (range 2-16) treatments at 4-6 week intervals at 7.75-9.5 J/cm(2). Average surface area treated was 24.0% with 88.6% average clearance after 1 year. Average clearance was 90.7% for lesions covering <20% surface area and 85.6% for lesions > or =20%. Location (V1, V2, V3, eye, and/or scalp), treated surface area, treatment number, and fluence predicted clearance. Average clearance for sole involvement of V1 was highest (at 93.8%), followed by V2 (at 91.1%), V3 (at 84.3%), V1/V2 (at 83.7%), V1/V2/V3 (at 81.0%), periocular (at 88.6%), and scalp (at 89.9%). All patients tolerated the higher treatment fluences without atrophy or scarring. DISCUSSION/CONCLUSIONS: Frequent, high energy pulsed-dye laser treatments are safe and highly effective in improving facial PWS in infants < or =6 months of age. Patients with PWS should be referred for pulsed-dye laser treatment during early infancy. PMID- 17868101 TI - Microscopic characterization of collagen modifications induced by low-temperature diode-laser welding of corneal tissue. AB - BACKGROUND AND OBJECTIVE: Laser welding of corneal tissue that employs diode lasers (810 nm) at low power densities (12-20 W/cm(2)) in association with Indocyanine Green staining of the wound is a technique proposed as an alternative to conventional suturing procedures. The aim of this study is to evaluate, by means of light (LM) and transmission electron microscopy (TEM) analyses, the structural modifications induced in laser-welded corneal stroma. MATERIALS AND METHODS: Experiments were carried out in 20 freshly enucleated pig eyes. A 3.5 mm in length full-thickness cut was produced in the cornea, and was then closed by laser welding. Birefringence modifications in samples stained with picrosirius red dye were analyzed by polarized LM to assess heat damage. TEM analysis was performed on ultra-thin slices, contrasted with uranyl acetate and lead citrate, in order to assess organization and size of type I collagen fibrils after laser welding. RESULTS: LM evidenced bridges of collagen bundles between the wound edges, with a loss of regular lamellar organization at the welded site. Polarized LM indicated that birefringence properties were mostly preserved after laser treatment. TEM examinations revealed the presence of quasi-ordered groups of fibrils across the wound edges preserving their interfibrillar spacing. These fibrils appeared morphologically comparable to those in the control tissue, indicating that type I collagen was not denatured during the diode laser corneal welding. CONCLUSIONS: The preservation of substantially intact, undenatured collagen fibrils in laser-welded corneal wounds supported the thermodynamic studies that we carried out recently, which indicated temperatures below 66 degrees C at the weld site under laser irradiation. This observation enabled us to hypothesize that the mechanism, proposed in the literature, of unwinding of collagen triple helixes followed by fibrils "interdigitation" is not likely to occur in the welding process that we set up for the corneal suturing. PMID- 17868102 TI - In vivo quantification of fluorescent molecular markers in real-time by ratio imaging for diagnostic screening and image-guided surgery. AB - Future applications of "molecular diagnostic screening" and "molecular image guided surgery" will demand images of molecular markers with high resolution and high throughput (~ > or =30 frames/second). MRI, SPECT, PET, optical fluorescence tomography, hyper-spectral fluorescence imaging, and bioluminescence imaging do not offer such high frame rates. 2D optical fluorescence imaging can provide surface images with high resolution and high throughput. The ability to accurately quantify the fluorescence in vivo is critical to extract functional information of the disease state, however few methods are available. Here, a ratiometric 2D quantification method is introduced. Through mathematical modeling the performance was evaluated using optical properties that resembled biological tissues with the fluorescent marker Protoporhyrin IX. Experimentally the performance was evaluated in optical phantoms with different optical properties employing a novel prototype clinical imaging system. The clinical feasibility of real-time, image-guided surgery was demonstrated in patients undergoing prostatectomy. Discussed are the reasons why the introduced method leads to an increased quantification performance followed by modifications so it can be applied to novel fluorescent molecular markers as phthalocyanine 4 and dual fluorescent markers. These offer additional advantages as these can provide a linear response to marker concentration and further minimize the dependence on autofluorescence and optical properties, as demonstrated through modeling. PMID- 17868103 TI - Photothermal antimicrobial nanotherapy and nanodiagnostics with self-assembling carbon nanotube clusters. AB - BACKGROUND AND OBJECTIVES: Unique properties of carbon nanotubes (CNTs) would open new avenues for addressing challenges to realize rapid and sensitive antimicrobial diagnostics and therapy for human pathogens. In this study, new CNTs' capabilities for photothermal (PT) antimicrobial nanotherapy were explored in vitro using Escherichia coli as a model bacterium. STUDY DESIGN/MATERIALS AND METHODS: Single-walled carbon nanotubes (SWNTs) and multi-walled carbon nanotubes (MWNTs) were incubated with E. coli K12 strain. CNTs' locations in bacteria and laser-induced thermal and accompanied effects around CNTs were estimated with TEM and PT microscopy, respectively. Multi-pulse lasers at 532 and 1064 nm with 12-ns pulse duration were used for irradiating sample mixtures at different laser fluences. Cell viability was evaluated using a bacterial viability test kit and epi-fluorescence microscopy. RESULTS: This study revealed CNTs' high binding affinity to bacteria, their capability to self-assemble as clusters at bacteria surfaces, and their inherent near-infrared (NIR) laser responsiveness. Cell viability was affected neither by CNTs alone nor by NIR irradiations alone. Notable changes in bacteria viability, caused by local thermal and accompanied bubble-formation phenomena, were observed starting at laser fluences of 0.1-0.5 J/cm(2) with complete bacteria disintegration at 2-3 J/cm(2) at both wavelengths. Furthermore, ethanol in reaction mixtures significantly (more than one order) enhanced bubble formation phenomena. CONCLUSION: This first application of laser activated CNTs as PT contrast antimicrobial agents demonstrated its great potential to cause irreparable damages to disease-causing pathogens as well as to detect the pathogens at single bacterium level. This unique integration of laser and nanotechnology may also be used for drinking water treatment, food processing, disinfection of medical instrumentation, and purification of grafts and implants. Furthermore, the significant ethanol-induced enhancement of bubble formation provides another unique possibility to improve the efficiency of selective nanophotothermolysis for treating cancers, wounds, and vascular legions. PMID- 17868105 TI - Laser removal of port wine stains: how close are we? A Commentary. PMID- 17868106 TI - Interstitial photodynamic therapy for a symptom-targeted treatment of complex vascular malformations in the head and neck region. AB - BACKGROUND AND OBJECTIVES: Photodynamic therapy is based on an interaction of a drug and light in oxygenated tissue. The photosensitizing drug Foscan is licensed in the EU for the treatment of advanced head and neck cancer. The light can be applied by surface illumination or directly into tumour tissue by optical fibres. One interesting feature of PDT is that it does not cause major damage to nerves and major blood vessels. This raises the possibility of using this therapy in the treatment of benign neoplasms in the head and neck. STUDY DESIGN/MATERIALS AND METHODS: A total of 11 patients with lymphatic [8] or venous malformation [3] were treated on 25 occasions. The treatments were carried out using Temoporphin (Foscan) 0.15 mg/kg; the drug-light-interval was 4 days. Illumination was performed at 652 nm delivered interstitially through bare tip fibres at a total light dose of 20 J per fibre. Multiple fibres were positioned either image guided [13] or clinically [12] to ensure accurate targeting of tissue while avoiding damage of the surrounding and overlying tissue. RESULTS: In all cases there was a significant reduction in the volume of abnormal tissue without damage to the overlying skin; the results were objectified using MRI-imaging, CT-volumetry and surface optical scanning. The best results were obtained with lymphatic malformations, especially for those that had not undergone previous surgery. Post treatment pain and swelling were successfully controlled with steroids and a variety of analgesics (opioids and non-steroidal anti-inflammatories). No vascular or neurological signs were encountered. CONCLUSION: This minimally invasive approach to treat complex benign neoplasias seems promising. The treatment is safe, effective and repeatable and merits further evaluation. PMID- 17868108 TI - Er:YAG laser osteotomy for removal of impacted teeth: clinical comparison of two techniques. AB - BACKGROUND AND OBJECTIVES: In contrast to many techniques currently employed for osteotomy, like saws, drills or modulated ultrasound, lasers offer non-contact and low-vibration bone cutting. Therefore, this report examines the benefits to laser osteotomy in oral surgery using two different short-pulsed Er:YAG laser systems. MATERIALS AND METHODS: Er:YAG lasers, using either a fiber-optic delivery system and an articulated arm delivery system, were used to remove impacted teeth in 30 patients. In 15 patients an Er:YAG laser utilizing a fiber optic delivery system was applied for cutting bone, with a pulse energy of 500 mJ, a pulse duration of 250 microseconds and frequency of 12 Hz (energy density 177 J/cm(2)). The other 15 patients were treated with an Er:YAG laser utilizing an articulated arm delivery system, with a pulse energy of 1,000 mJ, a pulse duration of 300 microseconds and a frequency of 12 Hz (energy density 157 J/cm(2)). RESULTS: In all cases the lasers allowed precise bone ablation without any visible, negative, thermal side-effects. Since the laser tip was used in a non-contact mode and could be positioned freely, unrestricted cut geometries were feasible. Adjacent soft tissue structures could be preserved and were not harmed by the laser beam. However, osteotomies were time consuming, especially if teeth had to be separated. The level of water irrigation limited the use of the laser. In 20% of the cases in which the articulated arm delivery laser was used to section teeth, it was necessary to use a conventional dental drill to finish the procedure. CONCLUSION: This bone ablation technique, using short Er:YAG laser pulses and water spray, produced good clinical results without any impairment to wound healing. However, for now, the lack of depth control and the time required to perform the necessary osteotomy limit routine clinical application. PMID- 17868109 TI - Endoscopic free electron laser technique development for minimally invasive optic nerve sheath fenestration. AB - PURPOSE: This study proposed to develop a technique for efficiently accessing the posterior orbital space using endoscopy and attempted application of free electron laser (FEL) energy, biopsy forceps, electrocautery, and CO(2) insufflation to posterior orbital tissues. METHODS: Through an inferior transconjunctival incision, access to the posterior orbital space was attempted in 14 eyes of 7 non-survival pigs. FEL energy (6.1 microm, 30 Hz, delivered via 250 microm hollow-glass waveguide), biopsy forceps, and monopolar electrocautery application were endoscopically attempted in the posterior orbit. CO(2) gas insufflation effects were assessed by analyzing arterial blood gases at 30-minute intervals for 1.5 hours. RESULTS: The posterior orbit was accessed in 13 of 14 eyes, the optic nerve was encountered, and FEL energy was applied in 8 of 14 eyes. Use of biopsy forceps and electrocautery were successful. Although ANOVA results for arterial blood gas changes were not statistically significant, visibility was adequate without CO(2) insufflation. CONCLUSIONS: The posterior orbit was endoscopically accessed and the optic nerve was exposed and successfully treated with FEL energy. CO(2) insufflation did not alter blood gases, but did not further enhance visibility in this study. PMID- 17868110 TI - The anti-inflammatory mechanism of 635 nm light-emitting-diode irradiation compared with existing COX inhibitors. AB - BACKGROUND AND OBJECTIVES: Inhibition of cyclooxygenase (COX) and prostaglandin E(2) (PGE(2)) protects cells against cell injury in specific pathophysiological situations: inflammation and oxidative stress. Although the anti-inflammatory effects have been reported in clinical fields for specific wavelength irradiation during wound healing, the physiological mechanism has not been clarified yet. The aim of the present study is to investigate the anti-inflammatory mechanism of 635 nm light-emitting-diode (LED) irradiation compared with existing COX inhibitors. STUDY DESIGN/MATERIALS AND METHODS: The present study investigated anti inflammatory effects of 635 nm irradiation on PGE(2) release, COX and phospholipase A(2) (PLA(2)) expression, and reactive oxygen species (ROS) dissociation in arachidonic acid (AA)-treated human gingival fibroblast (hGF). These results were compared with their existing COX inhibitors: indomethacin and ibuprofen. The PGE(2) release was measured by enzyme immunoassay, the COX expression was measured by western blot and reverse transcriptase polymerase chain reaction (RT-PCR), and ROS level was measured by flow cytometry, laser scanning confocal microscope and RT-PCR. RESULTS: Results showed that 635 nm irradiation and existing COX inhibitors inhibit expression of COX and PGE(2) release. Unlike indomethacin and ibuprofen, 635 nm irradiation leads to a decrease of ROS levels and mRNA expression of cytosolic phospholipase A(2) (cPLA(2)) and secretary phospholipase A(2) (sPLA(2)). CONCLUSION: Taken together, 635 nm irradiation, unlike indomethacin and ibuprofen, can directly dissociate the ROS. This inhibits cPLA(2), sPLA(2), and COX expression, and results in the inhibition of PGE(2) release. Thus, we suggest that 635 nm irradiation inhibits PGE(2) synthesis like COX inhibitor and appears to be useful as an anti inflammatory tool. PMID- 17868111 TI - Is cultured tendon fibroblast a good model to study tendon healing? AB - Cultured tendon fibroblasts (CTFs) from intact explants are widely used to study tendon healing in vitro. The significance of these findings may rely on similarities between CTFs and healing tendon fibroblasts in situ. Our purpose was to compare CTFs with fibroblasts cultured from healing tendons. We cultured CTFs from intact and healing tendons at day 7 and day 14 postinjury in a rat model of patellar donor site injury. The mRNA expression of COL1A1, COL3A1, decorin, and biglycan, with or without supplementation of 1 ng/mL TGF-beta1, was compared by quantitative real-time RT-PCR. The expression of proliferation cell nuclear antigen (PCNA) and alpha-smooth muscle actin (alpha-SMA) was determined by immunostain. COL3A1 and decorin mRNA in CTFs was lower as compared to day 7 healing fibroblasts, but its biglycan mRNA level was higher than day 14 healing fibroblasts. TGF-beta1 increased COL1A1 and decorin mRNA in CTFs, but decreased the mRNA of all four genes in day 7 healing tendon fibroblasts. CTFs exhibited lower PCNA immunopositivity as compared to day 7 and day 14 healing fibroblasts, but a higher alpha-SMA immunopositivity than cultured day 14 healing fibroblasts. These findings showed that CTFs did not resemble healing tendon cells with respect to major cellular activities related to tendon healing. Thus, fibroblasts from healing tendon may be a more appropriate model for studying cellular activities in tendon healing. PMID- 17868112 TI - The DEAD box RNA helicase VBH-1 is required for germ cell function in C. elegans. AB - Vasa and Belle are conserved DEAD box RNA helicases required for germ cell function. Homologs of this group of proteins in several species, including mammals, are able to complement a mutation in yeast (DED1) suggesting that their function is highly conserved. It has been proposed that these proteins are required for mRNA translation regulation, but their specific mechanism of action is still unknown. Here we describe functions of VBH-1, a C. elegans protein closely related to Belle and Vasa. VBH-1 is expressed specifically in the C. elegans germline, where it is associated with P granules, the C. elegans germ plasm counterpart. vbh-1(RNAi) animals produce fewer offspring than wild type because of defects in oocyte and sperm production, and embryonic lethality. We also find that VBH-1 participates in the sperm/oocyte switch in the hermaphrodite gonad. We conclude that VBH-1 and its orthologs may perform conserved roles in fertility and development. PMID- 17868113 TI - Introduction of a new interlocked intramedullary nailing device for stabilization of critically sized femoral defects in the rat: A combined biomechanical and animal experimental study. AB - The goals of this study were to develop a new intramedullary, rotation-stable locking device and evaluate it biomechanically and in vivo for maintenance of a critical size osteotomy gap in a model of conscious pseudarthrosis. In standardized osteotomized rat femora (5 mm osteotomy gap) two different rotation- and axial-stable locking devices (group pS + cS) were tested in vitro with respect to biomechanics and compared to a control group without an additional locking device (K; n = 6 for each group). For in vivo studies, 27 male Sprague Dawley rats (250-300 g) underwent a femoral defect osteotomy of critical size and were stabilized by one of the three methods (n = 9 for each group). All groups were examined radiologically postoperatively, after 14 days, and after 12 weeks. In vitro testing revealed higher compression and torsional rigidities for the two locking devices (p < 0.05) compared to the control group (compression rigidity: pS = 103.6 +/- 13.2; cS = 91.3 +/- 10.9; K = 52.8 +/- 8.4 N/mm; torsional rigidity: pS = 5.9 +/- 0.9; cS = 4.3 +/- 1.4; K = 0.4 +/- 0.1 Nmm/ degrees ). In vivo, group K and pS exhibited up to two thirds wire dislocation and reduction of the osteotomy gap, while dislocation was less frequent in the cS group. Thus, the locking device with compression of the wire showed advantages in rotational and axial stability for a critically sized defect, though the osteotomy gap could not be maintained in all cases over the 12-week period. Nevertheless, our data corroborate the necessity of an internal fixation device with sufficient axial and rotational stability. PMID- 17868114 TI - Microstructural adaptation in trapezial bone due to subluxation of the thumb. AB - Although the thumb saddle is one of the most common sites of degenerative osteoarthritis in the hand, little is known about the altered microstructure in osteoarthritic trapezial bones. External forces resulting from subluxation of the carpometacarpal joint of the thumb (CMC I) should provoke microstructural changes in the trapezium. The purpose of this study was to compare the regional differences of the microstructure between osteoarthritic and healthy trapezial bones. Fifteen trapezia harvested from female patients with radiologically and clinically diagnosed saddle joint osteoarthritis (OA) were compared with 15 unaffected controls. Microstructural parameters, such as bone volume ratio (BV/TV), three-dimensional connectivity (Conn.D), trabecular number (Tb.N), and trabecular thickness (Tb.Th) were studied using a microcomputed tomography (microCT) system. While the trapezial height in OA was 22% less, the sclerotic subchondral bone layer thickness was 50% higher in OA compared with the control group (p < 0.001). In the OA group there was a 42% higher bone volume ratio (p or =5; P = .009) and the presence of extracapsular spread (ECS) (P < .001) were independent risk factors for DM. In Group B, the presence of ECS (P = .008), poor differentiation (P = .040), pathological stage > or =III (P = .036), and the presence of neck recurrence (P = .001) were independent prognosticators. CONCLUSIONS: The current results indicated that different risk factor categories according to locoregional control may be used to facilitate the selection of appropriate management for patients with OSCC after they undergo radical surgery. PMID- 17868120 TI - Challenges and recommendations for advancing the state-of-the-science of quality of life assessment in symptom management trials. AB - Major findings are presented from a workshop on Quality of Life Assessment in Cancer Symptom Management Trials, sponsored by the National Cancer Institute. Data-driven research reports focused on 3 topics, 1) the rationale and utility of health-related quality of life (HRQOL) assessment, 2) conceptual models, and 3) measurement and design issues. Recommendations for including HRQOL assessment cited the potential value of: capturing additional treatment effects (eg, fatigue + depression); describing the patient experience; predicting patient prognosis; identifying potential adverse effects; observing interactions among symptoms; calculating quality adjusted survival and cost-effectiveness; and generating new hypotheses. Recommendations for developing more fully developed conceptual models focused on maintaining clear distinctions among symptoms, function, summary measures of HRQOL, and global HRQOL assessments; identifying symptom clusters; pursuing hypotheses about whether clustering is better explained as symptom related or as patient-related (genetic predispositions); and gaining a better understanding of the dynamic and reciprocal influences of symptoms on each other. With respect to measurement and design issues, because different HRQOL measures cover different domains with various degrees of sensitivity, there is a need to select measures that are carefully tailored to the study's hypotheses. Finally, there is a growing appreciation that trials must be powered to test for effects on secondary endpoints. PMID- 17868121 TI - Association between broadly defined bulimia nervosa and drug use disorders: common genetic and environmental influences. AB - OBJECTIVE: Previous research has shown an association between bulimia (BN) and drug use disorders (DUD). The purpose of the present study was to investigate possible influences on the comorbidity between BN and DUD. METHOD: Participants included 490 monozygotic and 354 dizygotic female twins and 930 females from opposite sex pairs. Multiple logistic regression analyses were used to test shared correlates and mediators. Bivariate twin analyses were used to investigate the contribution of genes and environment to the correlation between BN and DUD. RESULTS: Depression, neuroticism, and childhood sexual abuse (CSA) mediated the association between BN and DUD regardless of which disorder was used as the dependent variable. Analyses also indicated genetic and nonshared environmental overlap between BN and DUD. CONCLUSION: The association between BN and DUD is due mostly to overlapping genetic influences with a smaller contribution from nonshared environment. Depression, neuroticism, and CSA are likely important shared correlates. PMID- 17868122 TI - Classification of child and adolescent eating disturbances. Workgroup for Classification of Eating Disorders in Children and Adolescents (WCEDCA). AB - OBJECTIVE: : The purpose of this article is to summarize major conceptual and clinical variables related to age-appropriate and developmentally appropriate classification of eating problems and disorders in children and adolescents. METHOD: A review of current classifications and related literature in child development is provided. Problems with current classification schemes are identified and discussed. RESULTS: Current classifications are inadequate to address the clinical and research needs of children and adolescents with eating disturbances and disorders. CONCLUSION: A range of possible changes in classification strategies for eating disorders in children and adolescents are described. PMID- 17868123 TI - Stability of eating disorder diagnoses. PMID- 17868124 TI - Purging disorder: subthreshold variant or full-threshold eating disorder? AB - OBJECTIVE: To review evidence of the clinical significance, distinctiveness, and prevalence of a newly characterized form of eating disorder not otherwise specified, purging disorder (PD). METHOD: Articles were identified by computerized and manual searches. RESULTS: PD is a clinically significant disorder of eating that does not appear to differ meaningfully in severity from bulimia nervosa (BN). Preliminary evidence supports the distinctiveness of PD from BN, but no studies have directly examined PD in comparison with anorexia nervosa (AN). Epidemiological studies indicate that PD affects between 1.1 and 5.3% of young adult women in their lifetimes, reflecting lifetime prevalence rates comparable with those for AN and BN. CONCLUSION: More research on PD is needed, particularly with regard to etiology, treatment, course, and outcome. Such work would be greatly facilitated by standardization of the syndrome's definition. PMID- 17868125 TI - The multifaceted role of distress tolerance in dysregulated eating behaviors. AB - OBJECTIVE: Few empirical studies have examined the potential role of affect in dysregulated eating. The authors hypothesized that distress tolerance would predict EDI-Bulimia, even when controlling for several covariates, including depressive and anxiety symptoms, and all four subscales of the UPPS Impulsive Behavior Scale. Additionally, the authors predicted low levels of distress tolerance would interact with high levels of urgency to predict EDI-Bulimia. Finally, the authors predicted that distress tolerance would mediate the previously reported relationship between anxiety sensitivity and EDI-Bulimia. METHOD: A sample of undergraduates (N = 200) filled out a series of questionnaires pertaining to the variables of interest, including the Eating Disorder Inventory, UPPS Impulsive Behavior Scale, Distress Tolerance Scale, and Anxiety Sensitivity Index. RESULTS: All three hypotheses were supported by the data. CONCLUSION: Authors suggest that deficits in distress tolerance might play a significant role in the etiology and maintenance of bulimic symptoms. PMID- 17868126 TI - Epidemiology of eating disorders: creating opportunities to move the current classification paradigm forward. PMID- 17868127 TI - Specific and nonspecific comorbidity in anorexia nervosa. AB - OBJECTIVE: This article reports lifetime Axis I and II comorbidity in women with anorexia nervosa (AN), and ascertains specific and nonspecific comorbidity in AN compared to clinical samples of women with bulimia nervosa (BN) or major depression (DEP). METHOD: Outpatient AN (n = 56), BN (n = 132), and DEP (n = 100) samples were assessed using Structured Clinical Interviews I and II for DSM-III R. Baseline data were compared using univariate statistics and logistic regression. RESULTS: In the AN sample as a whole, specific elevations were found for prevalences of obsessive compulsive disorder. The AN-binge eating purging subtype (AN-BP) and the BN sample had elevated prevalences of Cluster B personality disorders. Cluster C prevalences were elevated across samples. CONCLUSION: Evidence of AN-specific, eating disorder-specific, and nonspecific comorbidity illustrates the heterogeneity in AN. Further research is need to examine the relative impact of specific and nonspecific comorbidity in AN subtypes and AN as a whole. PMID- 17868128 TI - A comparison of early family life events amongst monozygotic twin women with lifetime anorexia nervosa, bulimia nervosa, or major depression. AB - OBJECTIVES: To investigate the differential profile of early family life events associated with lifetime anorexia nervosa (AN), bulimia nervosa (BN), and major depression (MD). METHOD: Only data from the monozygotic twins (n = 622) were examined from a community sample of female twins who had participated in three waves of data collection. Eating disorder and MD diagnoses were ascertained from the Eating Disorder Examination at Wave 3 and interview at Wave 2 respectively. Early family events were ascertained from self-report measures at Waves 1 and 3. Two case control designs were used, including a comparison of women: (1) who had lifetime AN, BN, MD, and controls, and (2) twin pairs discordant for either AN, BN, or MD (where the unaffected cotwin formed the control group). RESULTS: Across the two types of designs, compared to controls, both AN and BN were associated with more comments from the family about weight and shape when growing up. AN was uniquely associated with higher levels of paternal protection while BN was associated with higher levels of parental expectations. CONCLUSION: While some overlap among early life events was indicated, especially related to parental conflict and criticism, there was evidence to support some degree of nonoverlap among life events associated with AN, BN, and MD. PMID- 17868129 TI - Genetic epidemiology of eating disorders and co-occurring conditions: the role of endophenotypes. PMID- 17868130 TI - Thinking afresh about the classification of eating disorders. PMID- 17868131 TI - Transcription factor TEAD2 is involved in neural tube closure. AB - TEAD2, one of the first transcription factors expressed at the beginning of mammalian development, appears to be required during neural development. For example, Tead2 expression is greatest in the dorsal neural crest where it appears to regulate expression of Pax3, a gene essential for brain development. Consistent with this hypothesis, we found that inactivation of the Tead2 gene in mice significantly increased the risk of exencephaly (a defect in neural tube closure). However, none of the embryos exhibited spina bifida, the major phenotype of Pax3 nullizygous embryos, and expression of Pax3 in E11.5 Tead2 nullizygous embryos was normal. Thus, Tead2 plays a role in neural tube closure that is independent of its putative role in Pax3 regulation. In addition, the risk of exencephaly was greatest with Tead2 nullizygous females, and could be suppressed either by folic acid or pifithrin-alpha. These results reveal a maternal genetic contribution to neural tube closure, and suggest that Tead2 deficient mice provide a model for anencephaly, a common human birth defect that can be prevented by folic acid. PMID- 17868132 TI - Optical disector counting in cryosections and vibratome sections underestimates particle numbers: effects of tissue quality. AB - Optical disector counting is currently applied most often to cryosections, followed in frequency by resin-embedded tissues, paraffin, and vibratome sections. The preservation quality of these embedding options differs considerably; yet, the effect of tissue morphology on numerical estimates is unknown. We tested whether different embedding media significantly influence numerical estimates in optical disector counting, using the previously calibrated trochlear motor nucleus of hatchling chickens. Animals were perfusion-fixed with paraformaldehyde (PFA) only or in addition with glutaraldehyde (GA), or by Methacarn immersion fixation. Brains were prepared for paraffin, cryo-, vibratome or celloidin sectioning. Complete penetration of the thionin stain was verified by z-axis analysis. Neuronal nuclei were counted using an unbiased counting rule, numbers were averaged for each group and compared by ANOVA. In paraffin sections, 906 +/- 12 (SEM) neurons were counted, similar to previous calibrated data series, and results obtained from fixation with Methacarn or PFA were statistically indistinguishable. In celloidin sections, 912 +/- 28 neurons were counted-not statistically different from paraffin. In cryosections, 812 +/- 12 neurons were counted (underestimate of 10.4%) when fixed with PFA only, but 867 +/- 17 neurons were counted when fixed with PFA and GA. Vibratome sections had the most serious aberration with 729 +/- 31 neurons-a deficit of 20%. Thus, our analysis shows that PFA-fixed cryosections and vibratome sections result in a substantial numerical deficit. The addition of GA to the PFA fixative significantly improved counts in cryosections. These results may explain, in part, the significant numerical differences reported from different labs and should help investigators select optimal conditions for quantitative morphological studies. PMID- 17868133 TI - A novel method for three-dimensional observation of the vascular networks in the whole mouse brain. AB - A novel method for acquiring serial images suitable for three-dimensional reconstruction of vascular networks in the whole brain of mouse was developed. The brain infused with a White India ink-gelatin solution was fixed and embedded in paraffin containing Sudan Black B through xylene also containing Sudan Black B. Each sliced surface of the paraffin block was coated with liquid paraffin and its image was serially acquired. Coating with liquid paraffin extremely improved the quality of the image. The series of serial images was free of distortion and a three-dimensional image was reconstructed without the problem of the alignment and registration of adjacent images. The volume-rendered image indicated three dimensional distribution of blood vessels in a whole brain. No ghost or shadow was observed on a volume-rendered image of the White India ink-gelatin infused brain. The z-axial resolution examined on the orthogonal sections reconstituted from serial images obtained at an interval of 5 mum showed no cross talk, indicating that the z-axial resolution was no larger than 5 mum. A proper understanding of the vascular system in a whole brain is indispensable to reveal the development of the vascular system in the brain of normal and genetically manipulated mouse and vascular alterations in pathological situation, such as stroke and neurodegenerative disease. Although simple and inexpensive, this method will provide fundamental information on the vascular system in a whole brain. PMID- 17868134 TI - Study of the spinal cords of the sturgeon Acipenser schrenckii, gar Lepisosteus oculatus, and goldfish Carassius auratus by morphological, immunohistochemical, and biochemical approaches. AB - Little is known about the spinal cords of phylogenetically ancient actinopterygeans. The spinal cords of the chondrostean Acipenser schrenckii (Amur sturgeon), holostean Lepisosteus oculatus (spotted gar), and teleost Carassius auratus (goldfish) were, therefore, analyzed by immunohistochemistry, electron microscopy and two-dimensional gel electrophoresis. Morphology showed numerous similarities between sturgeons and gars. In both, a dorsal column between the two dorsal horns was lacking, giving the grey matter an inverted Y-shape. In goldfish, a small dorsal column was seen, the grey matter occupied a larger area, neuronal density was much higher, and a ventral commissure was apparent, which was absent in sturgeons and gars. In the white matter of sturgeons and gars, small caliber axons predominated, whereas larger axons were frequent in goldfish. Choline acetyltransferase immunoreactive neurons were prevalent in the ventral horns of all three fish, mainly in motoneurons, but stained fibers were only found in sturgeons and gars. gamma-aminobutyric acid positive cells were seen in both the ventral and the dorsal horns of all three fish. Distribution of serotonin (5-HT) and tyrosine hydroxylase (TH) immunoreaction was similar in sturgeons and gars, being located in both the ventral and the dorsal horns. In goldfish, 5-HT label was confined to the ventral horn and TH label was mainly observed in a cell group located ventromedially. Two-dimensional gel electrophoresis showed a gradual increase in protein number from sturgeons to gars to goldfish. In conclusion, the spinal cords of sturgeons and gars share many morphological and chemical features, distinguishing them from the goldfish spinal cord. PMID- 17868135 TI - Caldesmon is necessary for maintaining the actin and intermediate filaments in cultured bladder smooth muscle cells. AB - Caldesmon (CaD), a component of microfilaments in all cells and thin filaments in smooth muscle cells, is known to bind to actin, tropomyosin, calmodulin, and myosin and to inhibit actin-activated ATP hydrolysis by smooth muscle myosin. Thus, it is believed to regulate smooth muscle contraction, cell motility and the cytoskeletal structure. Using bladder smooth muscle cell cultures and RNA interference (RNAi) technique, we show that the organization of actin into microfilaments in the cytoskeleton is diminished by siRNA-mediated CaD silencing. CaD silencing significantly decreased the amount of polymerized actin (F-actin), but the expression of actin was not altered. Additionally, we find that CaD is associated with 10 nm intermediate-sized filaments (IF) and in vitro binding assay reveals that it binds to vimentin and desmin proteins. Assembly of vimentin and desmin into IF is also affected by CaD silencing, although their expression is not significantly altered when CaD is silenced. Electronmicroscopic analyses of the siRNA-treated cells showed the presence of myosin filaments and a few surrounding actin filaments, but the distribution of microfilament bundles was sparse. Interestingly, the decrease in CaD expression had no effect on tubulin expression and distribution of microtubules in these cells. These results demonstrate that CaD is necessary for the maintenance of actin microfilaments and intermediate-sized filaments in the cytoskeletal structure. This finding raises the possibility that the cytoskeletal structure in smooth muscle is affected when CaD expression is altered, as in smooth muscle de-differentiation and hypertrophy seen in certain pathological conditions. PMID- 17868136 TI - Movement of stress fibers away from focal adhesions identifies focal adhesions as sites of stress fiber assembly in stationary cells. AB - Force generated in contractile actin filament bundles (stress fibers-SFs) is transmitted to the extracellular matrix (ECM) via linker proteins and transmembrane integrins at focal adhesions (FAs). Though it has long been known that actin is rapidly exchanged in FAs, the connection between SFs and FAs has not been studied in detail. We introduced fiduciary marks on SFs by expressing GFP-palladin or GFP-alpha-actinin-1, which are both FA and dense body proteins, and by pattern bleaching of GFP-actin. Following fiduciary marks on SFs over time by time-lapse fluorescence microscopy, we detected assembly of SFs at FAs in stationary cells resulting in movement of SFs away from FAs with a velocity of 0.2-0.4 microm/min. Visualization of FAs in GFP-palladin/DsRed-paxillin double transfected cells showed that SF elongation was not accompanied by a change in FA length. SF elongation at FAs depended on actin polymerization and force as demonstrated by inhibitors of actin polymerization (cytochalasin D, jasplakinolide) and inhibitors of myosin-dependent contraction (blebbistatin, Y 27632), respectively. Our finding of SF assembly at FAs has important implications for SF formation, force transmission, and tension distribution within the actin cytoskeletal network of stationary cells. PMID- 17868137 TI - A modified model of hindlimb osteomyocutaneous flap for the study of tolerance to composite tissue allografts. AB - Composite tissue allotransplantation (CTA) is the new frontier in transplantation. More than 25 hand allograft transplants have been performed worldwide, and the feasibility has been well established. The classical experimental model of CTA involves rat orthotopic hindlimb transplantation, a time-consuming procedure associated with high mortality and morbidity. We describe a rat heterotopic osteomyocutaneous flap that serves as a nonfunctional CTA, allowing the study of tolerance induction to a highly antigenic vascularized allograft of bone, muscle, and skin while minimizing the morbidity and mortality of full hind limb transplantation. In the present studies, we explored whether establishing chimerism by nonmyeloablative conditioning would induce tolerance to CTA. When compared with the classic hind limb transplantation model, these results demonstrate that our heterotopic hind limb flap is less morbid and as an effective experimental model for the study of CTA tolerance. PMID- 17868138 TI - Clinical experience with the nasolabial fold as receptor site in microvascular reconstruction. AB - We report our experience using the vessels at the nasolabial fold as receptor site in free tissue transfer in head and neck reconstructions; a site that proved more convenient than the submandibulary site in selected cases. Six cases as well as the dissection technique of the nasolabial fold are reported. No complications occurred during or post surgery and in all cases the vessels were of adequate diameter for an end to end anastomosis. The advantages this site offers are discussed. PMID- 17868139 TI - The use of integra artificial dermis to minimize donor-site morbidity after suprafascial dissection of the radial forearm flap. AB - In an effort to minimize the radial forearm flap donor-site morbidity, the flap was elevated using the suprafascial dissection technique, in six patients with various facial defects. The donor site was covered primarily with Integra artificial skin and secondarily with an ultrathin split-thickness skin graft. The mean time to wound healing of the forearm donor site was 24 days. There were no flap failures, and all flaps healed uneventfully. At the end of the follow-up, all patients showed normal range of motion of the wrist and the fingers, normal power grip, and power pinch. All patients evaluated the esthetic appearance of the forearm donor site as very good. In conclusion, suprafascial dissection of the forearm flap creates a superior graft recipient site, and the use of Integra artificial dermis is a valuable advancement to further minimize the donor-site morbidity, resulting in excellent functional and aesthetic outcomes. PMID- 17868140 TI - Free SCIA/SIEA skin flap: a dual blood supply approach to groin region. AB - Free groin flap donor skin is unequaled in generous skin supply and inconspicuousness. We reliably utilize this region by taking advantage of the dual blood supply from superficial circumlex iliac (SCIA) and superficial inferior epigastric (SIEA) arteries and name the flap "Free SCIA/SIEA skin flap." The arterial pedicle is selected between SCIA and SIEA according to vascular anatomy which is explored through an incision along the inguinal ligament prior to skin island planning. Among 57 free SCIA/SIEA skin flap transfers, two flap failures occurred; circulatory impairment was restored by taking the patient back to the operating room in four cases; major size discrepancy was noted in one end to-end arterial anastomosis; and no vein grafts were required. Mostly an extended length of skin island is harvested irrespective of wound size in order to utilize the proximal skin as a vascular carrier that compensates for short pedicle. We conclude that, with the current microsurgical expertise, free SCIA/SIEA skin flap is versatile even when the skin quality is considered. PMID- 17868141 TI - Early reintervention of compromised free flaps improves success rate. AB - INTRODUCTION AND AIM: To develop a protocolized monitor schedule in microvascular free flap reconstruction, we investigated a possible correlation between the outcome and the interval between clamp release and start of revision. MATERIALS AND METHODS: All the charts of patients treated between 2000 and 2006 with a free flap were evaluated. The patients who underwent a flap revision were further analyzed. RESULTS: A total of 608 free flaps were evaluated; 69 of these flaps were revised. Most vascular complications took place within the first 24 h; the latest complication was observed 8 days after surgery. After 6 days post surgery, the number of revisions decreased considerably. With regard to the salvaged flaps the mean time to start the revision was 46.5 h (SD 39). With regard to the failed revisions, the mean time to start the revision was 82.0 h (SD 47). This difference proved significant (P = 0.006). CONCLUSION: Our data shows that the majority of anastomotic failures occur within the first 24 h. Thereafter, the frequency of failures decreases. We also found that the time between initial reconstruction and start of the salvage procedure influences the outcome of the revision negatively. PMID- 17868142 TI - Surgical treatment of superimposed nerve compressions in hepatitis C neuropathy. AB - The plastic surgeon's usual involvement in patients with hepatitis C is most frequently limited to an inner city population with hand and forearm abscesses from intravenous drug use or to incidences of needle-stick injury in the operating room when the patient is hepatitis C positive. Hand surgeons and peripheral nerve surgeons often treat patients with underlying neuropathies who have superimposed overlying nerve compressions such as carpal tunnel syndrome. We have applied this experience to a patient with underlying peripheral neuropathy associated with Hepatitis C and clinical evidence of overlying lower extremity nerve compressions. We believe that she is the first successful surgical treatment of peripheral nerve compressions in a patient with hepatitis C associated neuropathy, documented by noninvasive neurosensory testing. PMID- 17868143 TI - Reconstruction of the human median nerve in the forearm with the Neurotube. AB - Reconstruction of the median nerve in the forearm traditionally has required multiple interfascicular interposition autologous nerve grafts. Recovery of two point discrimination, even in young adults, has been reported rarely. Two patients, aged 43 and 61, are reported with 5-year follow-up of median nerve reconstruction in the distal forearm in which multiple interposition bioabsorbable polyglycolic acid conduits (Neurotube) were used to bridge the 3-cm nerve defects. Four separate 2.3-mm diameter, 4.0-cm long conduits were used in each patient. Sensory re-education was used for rehabilitation. Each patient recovered two-point discrimination with good localization in the thumb, index, and middle finger by 2 years after the nerve reconstruction. Both patients recovered abductor pollicis brevis function. PMID- 17868144 TI - Selection of recipient vessels in microsurgical free tissue reconstruction of head and neck defects. AB - The development of microsurgical techniques has facilitated proper management of extensive head and neck defects and deformities. Bone or soft tissue can be selected to permit reconstruction with functional and aesthetic results. However, for free tissue transfer to be successful, proper selection of recipient vessels is as essential as the many other factors that affect the final result. In this article selection strategies for recipient vessels for osteocutaneous free flaps, soft tissue free flaps, previously dissected and irradiated areas, recurrent and subsequent secondary reconstructions, simultaneous double free flap transfers in reconstruction of extensive composite head and neck defects, and the selection of recipient veins are reviewed in order to provide an algorithm for the selection of recipient vessels for head and neck reconstruction. PMID- 17868145 TI - Microsurgical arterovenous loops and biological templates: a novel in vivo chamber for tissue engineering. AB - BACKGROUND: Microsurgical tissue engineering is an emerging topic in regenerative medicine. Here we describe a new microsurgical model of bioengineering in rats based on the use of an arterovenous loop (AV) implanted into a commercially available crosslinked collagen/glycosaminoglycan template. METHODS: The microvascular loop was created between the femoral artery and vein and covered by the template folded onto itself. The chamber was isolated from the outside tissue by an outer silicon layer to impede tissue ingrowth. RESULTS: At 1-month postimplantation, the tissue chamber was found heavily vascularized, as assessed by laser Doppler perfusion analysis. Histological examination showed that the AV loop was integrated into the collagen matrix of the template and that the whole template was filled with a newly formed soft connective tissue. Most interestingly, the whole scaffold was found heavily vascularized, including the formation of a large number of alpha-SMA-positive arterioles. CONCLUSIONS: The developed microsurgical chamber provides a highly vascular, isolated tool for in vivo tissue engineering. PMID- 17868146 TI - Population differences in the International Multi-Centre ADHD Gene Project. AB - The International Multi-Centre ADHD Gene sample consists of 674 families from eight countries (Belgium, England, Germany, Holland, Ireland, Israel, Spain, and Switzerland) ascertained from clinics for combined-type attention definity hyperactivity disorder in an offspring. 863 SNPs were successfully genotyped across 47 autosomal genes implicated in psychiatric disorders yielding a single nucleotide polymorphism (SNP) density of approximately one SNP per 2.5 kb. A global test of heterogeneity showed 269 SNPs nominally significant (expected 43). Inclusion of the Israeli population accounted for approximately 70% of these nominally significant tests. Hardy-Weinberg equilibrium tests suggest that combining all these populations would induce stratification, but that the Northern European populations (Belgium, England, Germany, Holland, and Ireland) could be appropriate. Tag SNPs were generated using pair-wise and aggressive tagging from Carlson et al. [2004] and de Bakker et al. [2005], respectively, in each population and applied to the other populations. Cross-population performance across Northern Europe was consistent with within population comparisons. Smaller sample size for each population tended to yield more problems for the generation of aggressive tags and the application of pair-wise tags. Any case-control sample employing an Israeli sample with Northern Europeans must consider stratification. A Northern European tag set, however, appears to be appropriate for capturing the variation across populations. PMID- 17868148 TI - Novel culture strategy for human stem cell proliferation and neuronal differentiation. AB - Embryonal carcinoma (EC) stem cells derived from germ cell tumors closely resemble embryonic stem (ES) cells and are valuable tools for the study of embryogenesis. Human pluripotent NT2 cell line, derived from a teratocarcinoma, can be induced to differentiate into neurons (NT2-N) after retinoic acid treatment. To realize the full potential of stem cells, developing in vitro methods for stem cell proliferation and differentiation is a key challenge. Herein, a novel culture strategy for NT2 neuronal differentiation was developed to expand NT2-N neurons, reduce the time required for the differentiation process, and increase the final yields of NT2-N neurons. NT2 cells were cultured as 3D cell aggregates ("neurospheres") in the presence of retinoic acid, using small-scale stirred bioreactors; it was possible to obtain a homogeneous neurosphere population, which can be transferred for further neuronal selection onto coated surfaces. This culturing strategy yields higher amounts of NT2-N neurons with increased purity compared with the amounts routinely obtained with static cultures. Moreover, mechanical and enzymatic methods for neurosphere dissociation were evaluated for their ability to recover neurons, trypsin digestion yielding the best results. Nevertheless, the highest recoveries were obtained when neurospheres were collected directly to treated surfaces without dissociation steps. This novel culture strategy allows drastic improvement in the neuronal differentiation efficiency of NT2 cells, insofar as a fourfold increase was obtained, reducing simultaneously the time needed for the differentiation process. The culture method described herein ensures efficient, reproducible, and scaleable ES cell proliferation and differentiation, contributing to the usefulness of stem cell bioengineering. PMID- 17868147 TI - PGE(2) receptor EP1 renders dopaminergic neurons selectively vulnerable to low level oxidative stress and direct PGE(2) neurotoxicity. AB - Oxidative stress and increased cyclooxygenase-2 (COX-2) activity are both implicated in the loss of dopaminergic neurons from the substantia nigra (SN) in idiopathic Parkinson's disease (PD). Prostaglandin E(2) (PGE(2)) is one of the key products of COX-2 activity and PGE(2) production is increased in PD. However, little is known about its role in the selective death of dopaminergic neurons. Previously, we showed that oxidative stress evoked by low concentrations of 6 hydroxydopamine (6-OHDA) was selective for dopaminergic neurons in culture and fully dependent on COX-2 activity. We postulated that this loss was mediated by PGE(2) acting through its receptors, EP1, EP2, EP3, and EP4. Using double-label immunohistochemistry for specific EP receptors and tyrosine hydroxylase (TH), we identified EP1 and EP2 receptors on dopaminergic neurons in rat SN. EP2 receptors were also found in non-dopaminergic neurons of this nucleus, as were EP3 receptors, whereas the EP4 receptor was absent. PGE(2), 16-phenyl tetranor PGE(2) (a stable synthetic analogue), and 17-phenyl trinor PGE(2) (an EP1 receptor selective agonist) were significantly toxic to dopaminergic cells at nanomolar concentrations; EP2- and EP3-selective agonists were not. We challenged dopaminergic neurons in embryonic rat mesencephalic primary neuronal cultures and tested whether these receptors mediate selective 6-OHDA toxicity. The nonselective EP1-3 receptor antagonist AH-6809 and two selective EP1 antagonists, SC-19220 and SC-51089, completely prevented the 40%-50% loss of dopaminergic neurons caused by exposure to 5 muM 6-OHDA. Together, these results strongly implicate PGE(2) activation of EP1 receptors as a mediator of selective toxicity in this model of dopaminergic cell loss. PMID- 17868149 TI - Cellular and molecular characterization of oxidative stress in olfactory epithelium of Harlequin mutant mouse. AB - Oxidative stress in the olfactory system is a major factor associated with age related olfactory impairment, although the mechanisms by which this occurs are not completely understood. The Harlequin mutant mouse (Hq/Y), which carries an X linked recessive mutation in the Aifm1 gene, is a model of progressive oxidative stress-induced neurodegeneration in the cerebellum and retina. To determine whether the Hq/Y mutant mouse is a suitable model of oxidative stress-associated olfactory aging, we investigated cellular and molecular changes in the olfactory epithelium (OE) and olfactory bulb (OB) of 6-month-old male Hq/Y mice compared to those in sex-matched littermate controls (+/Y) and in age- and sex-matched C57BL/6 mice. Immunoreactivity for apoptosis-inducing factor, the protein product of Aifm1, was localized in mature olfactory sensory neurons (mOSNs) in +/Y mice but was rarely detected in Hq/Y mice. Hq/Y mice also exhibited increased lipofuscin autofluorescence and increased immunoreactivity for an oxidative DNA/RNA damage marker in mOSNs and in mitral/tufted cells in the OB and an increased number of cleaved caspase-3 immunoreactive apoptotic cells in the OE. Microarray analysis demonstrated that Aifm1 expression was down-regulated by 80% in the OE of Hq/Y mice compared to that in +/Y mice. Most significantly, regulated genes were classified into functional categories of cell signaling/apoptosis/cell cycle, oxidative stress/aging, and cytoskeleton/extracellular matrix/transport-associated. Analysis with EASE software indicated that the functional categories significantly overrepresented in Hq/Y mice included up-regulated mitochondrial genes and down-regulated cytoskeletal organization- and neurogenesis-related genes. Our results strongly support the Hq/Y mutant mouse being a novel model for mechanistic studies of oxidative stress-associated olfactory aging. PMID- 17868150 TI - Inhibition of proteoglycan synthesis affects neuronal outgrowth and astrocytic migration in organotypic cultures of fetal ventral mesencephalon. AB - Grafting fetal ventral mesencephalon has been utilized to alleviate the symptoms of Parkinson's disease. One obstacle in using this approach is the limited outgrowth from the transplanted dopamine neurons. Thus, it is important to evaluate factors that promote outgrowth from fetal dopamine neurons. Proteoglycans (PGs) are extracellular matrix molecules that modulate neuritic growth. This study was performed to evaluate the role of PGs in dopamine nerve fiber formation in organotypic slice cultures of fetal ventral mesencephalon. Cultures were treated with the PG synthesis inhibitor methyl-umbelliferyl-beta-D xyloside (beta-xyloside) and analyzed using antibodies against tyrosine hydroxylase (TH) to visualize dopamine neurons, S100beta to visualize astrocytes, and neurocan to detect PGs. Two growth patterns of TH-positive outgrowth were observed: nerve fibers formed in the presence of astrocytes and nerve fibers formed in the absence of astrocytes. Treatment with beta-xyloside significantly reduced the distance of glial-associated TH-positive nerve fiber outgrowth but did not affect the length of the non-glial-associated nerve fibers. The addition of beta-xyloside shifted the nerve fiber growth pattern from being mostly glial guided to being non-glial-associated, whereas the total amount of TH protein was not affected. Further, astrocytic migration and proliferation were impaired after beta-xyloside treatment, and levels of non-intact PG increased. beta-Xyloside treatment changed the distribution of neurocan in astrocytes, from being localized in vesicles to being diffusely immunoreactive in the processes. To conclude, inhibition of PG synthesis affects glial-associated TH-positive nerve fiber formation in ventral mesencephalic cultures, which might be an indirect effect of impaired astrocytic migration. PMID- 17868151 TI - Mode of cembranoid action on embryonic muscle acetylcholine receptor. AB - The mechanism of eupalmerin acetate (EUAC) actions on the embryonic muscle nicotinic acetylcholine receptor (nAChR) in BC3H-1 cells was studied by using whole-cell and single-channel patch-clamp current measurements. With whole-cell currents, EUAC did not act as an agonist on this receptor. Coapplication of 30 microM EUAC with 50 microM, 100 microM, or 500 microM carbamoylcholine (CCh) reversibly inhibited the current amplitude, whereas, with 20 microM CCh, current was increased above control values in the presence of EUAC. EUAC concentration curves (0.01-40 microM) obtained with 100 microM and 500 microM CCh displayed slope coefficients, n(H), significantly smaller than one, suggesting that EUAC bound to several sites with widely differing affinities on the receptor molecule. The apparent rate of receptor desensitization in the presence of EUAC and CCh was either slower than or equal to that obtained with CCh alone. The major finding from single-channel studies was that EUAC did not affect single-channel conductance or the ability of CCh to interact with the receptor. Instead, EUAC acted by increasing the channel closing rate constant. The results are not consistent with the competitive model for EUAC inhibition, with the sequential open-channel block model, or with inhibition by increased desensitization. The data are best accounted for by a model in which EUAC acts by closed-channel block at low concentrations, by positive modulation at intermediate concentrations, and by negative allosteric modulation of the open channel at high concentrations. PMID- 17868152 TI - Histological correlation of diffusion tensor imaging metrics in experimental spinal cord injury. AB - Diffusion tensor imaging (DTI) has the potential to provide important information about the integrity of white matter tracts in injured spinal cord tissue. It is thought that DTI-based transverse diffusivity (lambda(t)) reflects the state of myelin, whereas longitudinal diffusivity (lambda(l)) reflects axonal integrity. However, this has not been established in spinal cord injury (SCI). Therefore, we performed quantitative histologic analysis on 4- and 8-week post-SCI rodent spinal cords that had received a moderately severe injury at the T7 level and correlated the histology with lambda(t) and lambda(l) measured in vivo. Using antibodies specific to myelin and axonal process (i.e., neurofilament), the percent area of expression was determined in the dorsal, ventral, and lateral white matter from both rostral and caudal regions away from the epicenter of the injury site. The results suggest a positive correlation between lambda(t) and demyelination in many but not all regions. However, these studies failed to establish a correlation between lambda(l) and axonal damage. These results suggest that caution must be exercised in interpreting the DTI metrics in terms of tissue pathology in SCI. PMID- 17868153 TI - Proteomic analysis of embryonic stem cell-derived neural cells exposed to the antidepressant paroxetine. AB - Antidepressant drugs can have significant effects on the mood of a patient suffering from major depression or other disorders. The pharmacological actions of these drugs generally affect the uptake or metabolism of the neurotransmitters serotonin, noradrenalin, and, to a lesser extent, dopamine. However, many aspects of antidepressant action are not understood. We conducted a proteomic analysis in a neuronal cell culture model in an attempt to identify molecules important to the operation of pathways functionally relevant to antidepressant action. The model involved generating cultures containing mixed neural and glial cells by controlled differentiation of mouse embryonic stem cells, followed by exposure to 1 microM paroxetine for 14 days. After antidepressant exposure, we observed increased expression or modification of sepiapterin reductase (SPR), heat shock protein 9A, RAS and EF-hand domain containing, and protein disulfide isomerase associated 3 and decreased expression or modification of creatine kinase, actin, prohibitin, a T-cell receptor alpha chain, defensin-related cryptdin 5, and the intermediate filament proteins glial fibrillary acidic protein and vimentin. SPR, the most strongly up-regulated protein observed, controls production of tetrahydrobiopterin, an essential cofactor for the synthesis of many neurotransmitters including serotonin, making it a plausible and intriguing candidate protein for involvement in mood control and antidepressant drug action. SPR and the other proteins identified may represent links to molecular processes of importance to mood dysregulation and control, and their respective genes may be novel candidates for the study of antidepressant pharmacogenetics. PMID- 17868154 TI - Controlled assembly of silver(I)-pyridylfullerene networks. PMID- 17868155 TI - The role played by the alpha-helix in the unfolding pathway and stability of azurin: switching between hierarchic and nonhierarchic folding. AB - The role played by the alpha-helix in determining the structure, the stability and the unfolding mechanism of azurin was addressed by studying a helix-depleted azurin variant produced by site-directed mutagenesis. The protein structure was investigated by CD, 1D (1)H NMR, fluorescence spectroscopy measurements and MD simulations, whilst EPR, UV-visible and cyclic voltammetry experiments were carried out to investigate the geometry and the properties of the Cu(II) site. The effects of the alpha-helix depletion on the thermal stability and the unfolding pathway of the protein were determined by DSC, UV/visible and fluorescence measurements at increasing temperature. The results show that, in the absence of the alpha-helix segment, the overall protein structure is maintained, and that only the Cu site is slightly modified. In contrast, the protein stability is diminished by about 60% with respect to the wild-type azurin. Moreover, the unfolding pathway of the mutant azurin involves the presence of detectable intermediates. In comparison with previous studies concerning other small beta-sheet cupredoxins, the results as a whole support the hypothesis that the presence of the alpha-helix can switch the folding of azurin from a hierarchic to a nonhierarchic mechanism in which the highly conserved beta sheet core provides a scaffold for cooperative folding of the wild-type protein. PMID- 17868156 TI - Biochemical studies of the thermal effects on DNA modifications by the antitumor cisplatin and their repair. AB - Using biochemical methods, we have examined the effect of two factors that might play a role in the mechanism of the biological activity of cisplatin at elevated temperatures (>37 degrees C). We show that increased temperatures result in distinct alterations in the modification of the target DNA by cisplatin, and in the repair of these modifications. Our in vitro results support the view that the enhanced DNA-cross-linking efficiency of cisplatin and the lower efficiency of native DNA repair mechanisms at higher temperature play at least a partial role in the potentiation of the antitumor effects of cisplatin under conditions of mild hyperthermia. PMID- 17868157 TI - Increasing pH causes faster anion-and cation-transport rates through a synthetic ion channel. AB - Ion-channel mimics are able to transmit electrical signals across phospholipid membranes, and can be envisioned as nanoswitches for molecular electronics. Here, we reported the use of pH to alter ion-transport rates through a synthetic aminocyclodextrin ion channel. Both cation- and anion-transport rates were found to increase with an increase in pH due to the unique electrostatics of the multiple ammonium groups that line the channel pore. Such pH regulation of ion transport rates is unique and can be exploited for sensing applications. PMID- 17868158 TI - Conformation, dynamics, and insertion of a noncysteine-containing protegrin-1 analogue in lipid membranes from solid-state NMR spectroscopy. AB - Disulfide-bonded beta-hairpin structures are common among antimicrobial peptides. Disulfide bonds are known to be important for antimicrobial activity, but the underlying structural reason is not well understood. We have investigated the membrane-bound structure of a disulfide-deleted analogue of the antimicrobial peptide protegrin-1, in which the four Cys residues were replaced by Ala. The secondary structure, dynamics, and topology of this Ala-PG1 peptide in the membrane were determined by using magic-angle-spinning NMR spectroscopy. Conformation-dependent (13)C isotropic chemical shifts of multiple (13)C-labeled residues were obtained from 1D cross-polarization and direct-polarization spectra, and from 2D J-coupling-mediated (13)C-(13)C correlation spectra. Most labeled residues exhibited two conformations: a random coil and a beta-sheet structure. The dual-conformation property was present in both anionic lipid bilayers, which mimic the bacterial membrane, and zwitterionic cholesterol containing bilayers, which mimic the eukaryotic cell membrane. The mobility of the peptide was measured by using a 2D C-H dipolar-shift correlation experiment. The random-coil fraction was highly mobile whereas the beta-sheet component was rigid. (1)H spin diffusion from the lipid chains to the peptide indicates that the beta-sheet component was well inserted into the anionic membrane, but surface bound in the cholesterol-containing neutral membrane. Thus, the removal of disulfide bonds changed some PG-1 molecules to highly mobile random coils that were poorly associated with the lipid membrane, but other molecules retained a beta-sheet conformation and had a similar membrane-binding topology to the parent peptide. Thus, the reduced antimicrobial activity of Ala-PG1 was largely due to the reduced number of insertion-competent beta-sheet molecules, rather than uniformly weakened activity of identically structured peptides. PMID- 17868159 TI - Double-stranded DNA-templated oligonucleotide digestion triggered by triplex formation. PMID- 17868160 TI - On the absolute configuration in 1,4-dihydrothiazepine covalent complexes derived from inhibition of class A and C beta-lactamases with 6-methylidene penems. PMID- 17868161 TI - Virtual screening for selective allosteric mGluR1 antagonists and structure activity relationship investigations for coumarine derivatives. AB - A virtual screening study towards novel noncompetitive antagonists of the metabotropic glutamate receptor 1 (mGluR1) is described. Alignment-free topological pharmacophore descriptors (CATS) were used to encode the screening compounds. All virtual hits were characterized with respect to their allosteric antagonistic effect on mGluR1 in both functional and binding assays. Exceptionally high hit rates of up to 26 % were achieved, confirming the applicability of this virtual screening concept. Most of the compounds were found to be moderately active, however, one potent and subtype selective mGluR1 antagonist, 13 (IC(50): 0.362 microM, SEM +/-0.031; K(i): 0.753 microM, SEM +/ 0.048), based on a coumarine scaffold was discovered. In a following activity optimization program a series of coumarine derivatives was synthesized. This led to the discovery of potent (60, IC(50): 0.058 microM, SEM +/-0.008; K(i): 0.293 microM, SEM +/-0.022) and subtype selective (rmGluR5 IC(50): 28.6 microM) mGluR1 antagonists. From our homology model of mGluR1 we derived a potential binding mode within the allosteric transmembrane region. Potential interacting patterns are proposed considering the difference of the binding pockets between rat and human receptors. The study demonstrates the applicability of ligand-based virtual screening for noncompetitive antagonists of a G-protein coupled receptor, resulting in novel, potent, and selective agents. PMID- 17868162 TI - Allergic contact dermatitis and the endocannabinoid system: from mechanisms to skin care. PMID- 17868163 TI - Synthesis of conjugatable bisphosphonates for molecular imaging of large animals. PMID- 17868164 TI - Biomimetic high-valent non-heme iron oxidants for the cis-dihydroxylation and epoxidation of olefins. PMID- 17868165 TI - Gelation-assisted control over excitonic interaction in merocyanine supramolecular assemblies. PMID- 17868166 TI - Indirect electrochemical sensing of radicals and radical scavengers in biological matrices. PMID- 17868167 TI - Reversible topochemical transformation of a soft crystal of a coordination polymer. PMID- 17868169 TI - On the characterization of dynamic supramolecular systems: a general mathematical association model for linear supramolecular copolymers and application on a complex two-component hydrogen-bonding system. AB - A general mathematical model for the characterization of the dynamic (kinetically labile) association of supramolecular assemblies in solution is presented. It is an extension of the equal K (EK) model by the stringent use of linear algebra to allow for the simultaneous presence of an unlimited number of different units in the resulting assemblies. It allows for the analysis of highly complex dynamic equilibrium systems in solution, including both supramolecular homo- and copolymers without the recourse to extensive approximations, in a field in which other analytical methods are difficult. The derived mathematical methodology makes it possible to analyze dynamic systems such as supramolecular copolymers regarding for instance the degree of polymerization, the distribution of a given monomer in different copolymers as well as its position in an aggregate. It is to date the only general means to characterize weak supramolecular systems. The model was fitted to NMR dilution titration data by using the program Matlab, and a detailed algorithm for the optimization of the different parameters has been developed. The methodology is applied to a case study, a hydrogen-bonded supramolecular system, salen 4+porphyrin 5. The system is formally a two component system but in reality a three-component system. This results in a complex dynamic system in which all monomers are associated to each other by hydrogen bonding with different association constants, resulting in homo- and copolymers 4n5m as well as cyclic structures 6 and 7, in addition to free 4 and 5. The system was analyzed by extensive NMR dilution titrations at variable temperatures. All chemical shifts observed at different temperatures were used in the fitting to obtain the DeltaH degrees and DeltaS degrees values producing the best global fit. From the derived general mathematical expressions, system 4+5 could be characterized with respect to above-mentioned parameters. PMID- 17868168 TI - Fluorous-based small-molecule microarrays for the discovery of histone deacetylase inhibitors. PMID- 17868170 TI - Synthesis of highly modified DNA by a combination of PCR with alkyne-bearing triphosphates and click chemistry. AB - We report the combination of "click chemistry" with PCR by using alkyne-modified triphosphates for efficient and homogeneous labeling of DNA. A series of modified PCR products of different lengths (300, 900, and 2000 base pairs) were prepared by using a variety of alkyne- and azide-containing triphosphates and different polymerases. After intensive screening of real-time PCR methods, protocols were developed that allow the amplification of genes by using these modified triphosphates with similar efficiency to that of standard PCR. The click reaction on the highly modified PCR fragments provided conversion rates above 90 % and resulted in the functionalization of hundreds of alkynes on large DNA fragments with superb selectivity and efficiency. PMID- 17868171 TI - Evidence for the intermediacy of Wheland-Meisenheimer complexes in SEAr reactions of aminothiazoles with 4,6-dinitrobenzofuroxan. AB - Reactions of DNBF with a series of 2-aminothiazoles (1 a-f) to afford thermodynamically stable C-bonded sigma-adducts have been investigated in acetonitrile. A most significant finding emerged on recording NMR spectra immediately after mixing of equimolar amounts of DNBF and the unsubstituted 2 aminothiazole (1 a) in Me2SO: namely, that the formation of 9 a is preceded by that of a short-lived intermediate species X. From the 1H NMR parameters characterizing this intermediate, as well as the dependence of its lifetime on the experimental conditions-the presence of excess DNBF over 1 a increases the lifetime of X while an excess of base (1 a) accelerates its conversion into 9 a- it is convincingly demonstrated that the structure of X combines the presence of a positively charged Wheland complex moiety (with regard to the thiazole ring) with that of a negatively charged Meisenheimer complex moiety (with regard to the benzofuroxan system). So far, only one intermediate of this type (noted WM) has been successfully characterized, in the reactions of DNBF with 1,3,5-tris(N,N dialkylamino)benzenes. Among the key features supporting the intermediacy of X along the reaction coordinate leading to 9 a is the fact that the reactions of DNBF with 1 a in the presence of an alcohol (MeOH, EtOH, nPrOH) produce new adducts arising from the addition of an alcohol molecule to the thiazole moiety of WM-1 a. Reflecting the presence of three chiral centres, these species are formed as mixtures of several diastereomers that could all be characterized in their racemic forms in ethanol. These findings generalize the previous report on the formation of Wheland-Meisenheimer carbon-carbon complexes in homocyclic series. PMID- 17868172 TI - Formation of ZSM-22 zeolite catalytic particles by fusion of elementary nanorods. AB - An ZSM-22 aluminosilicate zeolite was synthesized using the hydrothermal gel method at 150 degrees C. Products obtained after different synthesis times were characterized using various techniques and catalytic testing. Massive formation of ZSM-22 nanocrystals occurs after only a short synthesis time, appearing as isolated rods with a cross section of 12+/-4 nm. Nanorods have aluminum enriched at their external surface. Later in the crystallization process nanorods align and fuse sideways, whereby the external surface is systematically converted into an internal micropore surface. The formation of aluminum bearing micropores by the joining of nanorod surfaces is responsible for the enhanced catalytic activity. For this, the zeolite synthesis of nanoscale crystallites is ineffective for enhancing catalytic activity. PMID- 17868173 TI - Configurational stability of oxymethyllithiums as intermediates in intramolecular rearrangements. AB - Several homochiral oxymethyllithiums, chiral by virtue of the hydrogen isotopes protium and deuterium, were prepared. They were tested for their microscopic configurational stability in intramolecular isomerizations, such as the silyl- and germyl-[1,2]-retro-Brook and the sigmatropic[2,3]-Wittig rearrangement. The influence of temperature, solvent, and migrating group on the stability of the intermediate carbanions was studied. Furthermore, the stereochemical course of these rearrangements was elucidated, resulting in highly enantioenriched alcohols (90-97% ee; ee=enantiomeric excess) up to temperatures of 0 degrees C. PMID- 17868174 TI - Multiresidue determination of thermolabile insecticides in cereal products by gas chromatography-mass spectrometry: evaluation with on-column injection and conventional hot splitless injection. AB - This communication presents a study on the simultaneous determination of thermolabile N-methylcarbamate and organophosphorus insecticides in cereal products by gas chromatography-mass spectrometry. The thermal stability of the multiple insecticides was evaluated with conventional hot splitless injection and on-column injection. The results obtained by GC-MS with these two injection techniques were compared in terms of the recovery, the limit of detection, the limit of qualification, and the reproducibility. With on-column injection, the pesticide recoveries in cereal samples were better than 82%, with relative standard deviations lower than 5.4%. The limits of qualification for most insecticides were in the range of 0.009-0.08 mg/kg, i. e. lower than the maximum residue limits established for insecticides in cereal products by the European Union. The long-term stability using on-column injection for analysis of insecticides in real samples was evaluated and normal chromatographic performance could be obtained within 50 analyses. The results revealed that it was possible for application of on-column injection in the analysis of thermolabile multiple insecticides in food sample after comprehensive sample clean-up, despite the highly contaminated nature of the column system. PMID- 17868175 TI - Determination of decabromodiphenyl ether in water samples by single-drop microextraction and RP-HPLC. AB - This paper describes the development of a new method using single-drop microextraction (SDME) and RP-HPLC for the determination of decabromodiphenyl ether (BDE-209) in water samples. The effects of SDME parameters such as extraction solvent, microdrop volume, extraction time, stirring speed, salt concentration, and sample pH on the extraction performance are investigated. Under optimal extraction conditions (extraction solvent, toluene; solvent drop volume, 3.0 microL; extraction time, 15 min; stirring speed, 600 rpm; no addition of salt and change of sample pH), the calibration curve was drawn by plotting peak area against a series of BDE-209 concentrations (0.001-1 microg/mL) in aqueous solution; the correlation coefficient (r) was 0.9998. The limit of detection was 0.7 ng/mL. The enrichment factor was 10.6. The precision of this method was obtained by six successive analyses of a 100 ng/mL standard solution of BDE-209, and RSD was 4.8%. This method was successfully applied to the extraction of BDE-209 from tap and East Lake water samples with relative recoveries ranging from 92.5 to 102.8% and from 91.5 to 96.2%, respectively, and the relative standard deviations (n = 3) were 4.4 and 2.2%. The proposed method is acceptable for the analysis of BDE-209 in water samples. PMID- 17868176 TI - A new method for simultaneous estimation of unsaponifiable constituents of rice bran oil using HPTLC. AB - Rice bran oil (RBO) is rich in a variety of bioactive phytochemicals otherwise known as unsaponifiable constituents (USC). Oryzanols, phytosterols, tocols, etc. are the major USC in RBO; the methods presently used for their estimation involve different techniques and require pretreatment of the sample. In this paper standardization of a simple method for simultaneous estimation of USC directly from RBO using HPTLC is presented. The method involves a two-stage separation of USC on a precoated silica gel 60 F(254 )TLC plate viz.: TLC-1 to separate sterols, oryzanols and tocols; TLC-2 to separate steryl esters, wax, and squalene. Calibration plots using the respective standards were made to determine LOD, LOQ, and linear regression equations. Recovery studies were also conducted and the values ranged from 93.45 to 101.97%. The LOD and LOQ values showed the sensitivity of the method. The instrumental precision was found to be in the range of 0.30 to 1.18 CV%. Quantitative estimation of USC in crude RBO and refined RBO using this method gave a concentration of 52.80 mg/g of USC in the crude and 33.48 mg/g in the refined oil. The present method for estimation of USC using HPTLC is fast, simple, accurate, precise, and sensitive, as demonstrated here. PMID- 17868177 TI - The rapid detection and identification of the impurities of simvastatin using high resolution sub 2 microm particle LC coupled to hybrid quadrupole time of flight MS operating with alternating high-low collision energy. AB - The profiling and identification of impurities in raw pharmaceuticals or finished drug product is an essential part of the pharmaceutical manufacturing process. Critical to this process is the ability to confirm known, expected impurities and identify new impurities. LC coupled to electrospray MS is a powerful tool that has been employed for the identification of impurities, natural products, drug metabolites, and proteins. In this study, we show how sub 2 microm porous particle LC has been coupled to hybrid quadrupole orthogonal TOF mass spectrometer to profile and identify the impurities of the common cholesterol lowering drug simvastatin. The hybrid quadrupole TOF mass spectrometer was operated by alternating the collision cell energies to allow for the rapid, facile conformation of the identity of impurities. Using this process it was possible to identify all of the common impurities of simvastatin in a single 10 min run. During the analysis a new impurity of simvastatin was detected and identified as the saturated ring form of simvastatin. PMID- 17868178 TI - Determination of sulphonamides in animal tissues by high performance liquid chromatography with pre-column derivatization of 9-fluorenylmethyl chloroformate. AB - A novel approach for simultaneous determination of 12 sulphonamides (sulphadiazine, sulphamethazine, sulphathiazole, sulphadimethoxine, sulphamerazine, sulphapyridine, sulphamethoxazole, suphamethizole, sulphaquinoxaline, sulphameter, sulphamonomethoxine, and sulphachloropyridazine) in animal tissues (swine muscle and liver, chicken muscle, beef muscle) by HPLC with UV detection has been developed. A pre-column derivatization of the sulphonamide compounds with 9-fluorenylmethyl chloroformate (FMOC-Cl) has been proposed and the reaction conditions have been optimized. The FMOC-sulphonamide derivatives were purified by SPE with silica gel as solid support prior to HPLC separation. The limits of detection for the sulphonamide compounds were greatly improved after the derivatization and purification step for the derivatives. Sulphonamide residues in animal tissues were extracted by acetonitrile and purified by solid phase extraction with C(18) as the solid support. The method developed has high sensitivity and good repeatability, and the average recoveries for most of the sulphonamides at various spiking levels were above 70% with relative standard deviations below 13.7%. The limits of detection for most sulphonamides can reach 3-5 microg/kg. PMID- 17868182 TI - Role of lattice strain and defects in copper particles on the activity of Cu/ZnO/Al(2)O(3) catalysts for methanol synthesis. PMID- 17868184 TI - Adiponectin gene therapy of streptozotocin-induced diabetic mice using hydrodynamic injection. AB - BACKGROUND: Adiponectin (Adipo), an adipocyte hormone involved in the regulation of glucose and lipid metabolism, has already been identified as a potential therapeutic target for the treatment of diabetes. However, successful delivery of Adipo to the receptors is difficult due to their peptide characteristics. Receptors for Adipo are abundantly expressed in the liver and skeletal muscle. METHODS: Uptake of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) in hepatoblastoma HepG2 cells expressing Adipo was examined. Adipo expressing plasmid DNA (10-50 microg) in saline solution (0.1 ml/g body weight) was rapidly injected into the tail vein of 4-week-old diabetic mice after 4-6 weeks of treatment with streptozotocin (STZ). Uptake of glucose in diabetic mice also was measured using a planar positron imaging system featuring 18 fluorodeoxyglucose. RESULTS: HepG2 cells expressing Adipo exhibited significantly increased 2-NBDG uptake compared with cells transfected with control plasmid even in the absence of insulin. STZ-induced diabetic mice showed decreased serum Adipo levels compared with non-diabetic mice. A single hydrodynamic injection of 10-50 microg Adipo-expressing plasmid DNA into diabetic mice led to approximately 10-15 fold elevation in serum Adipo levels, and resulted in decreased serum levels of glucose and triglyceride. As well as exhibiting higher levels of Adipo expression, diabetic mice also had higher hepatic glucose uptake than similar mice injected with control plasmid. CONCLUSIONS: We report that STZ-induced diabetic mice exhibited decreased Adipo levels and hyperglycemia which may be alleviated by hydrodynamic injection of the Adipo gene. This type of gene delivery system to the liver offers a different approach in developing novel treatments for type 1 and 2 diabetes. PMID- 17868185 TI - Caffeine, sleep and wakefulness: implications of new understanding about withdrawal reversal. AB - The broad aim of this review is to critically examine the implications of new understanding concerning caffeine withdrawal and withdrawal reversal in the context of research concerned with the effects of caffeine on sleep and wakefulness. A comprehensive search was conducted for relevant experimental studies in the PubMED and PsycINFO databases. Studies were assessed with particular reference to methodological adequacy for controlling against confounding due to caffeine withdrawal and withdrawal reversal. This assessment was used to clarify evidence of effects, highlight areas of ambiguity and derive recommendations for future research. It was found that researchers have generally failed to take account of the fact that habitual use of caffeine, even at moderate levels, leads to physical dependence evidenced by physiological, behavioural and subjective withdrawal effects during periods of abstinence. Consequently, there has been near-complete absence of adequate methodological controls against confounding due to reversal of withdrawal effects when caffeine is experimentally administered. The findings of what has been a substantial research effort to elucidate the effects of caffeine on sleep and wakefulness, undertaken over a period spanning decades, are ambiguous. Current shortcomings can be redressed by incorporating suitable controls in new experimental designs. PMID- 17868186 TI - Guidelines for good pharmacoepidemiology practices (GPP). PMID- 17868187 TI - Encapsulated human primary myoblasts deliver functional hFIX in hemophilic mice. AB - BACKGROUND: Hemophilia B is a bleeding disorder caused by defective factor IX (FIX), currently treated by regular infusions of plasma-derived or recombinant FIX. We propose a gene therapy strategy based on the implantation of cells secreting FIX enclosed in alginate microcapsules as a highly desirable alternative treatment. We have reported sustained delivery of human factor IX (hFIX) in immunocompetent mice implanted with encapsulated primary mouse myoblasts engineered to secrete hFIX. As a step towards the treatment of human patients, in this study we report the implantation of encapsulated human primary myoblasts secreting hFIX in hemophilia B mice. METHODS: Human primary myoblasts were transfected with plasmids pKL4M-hFIX, pLNM-betaIXL, pMFG-hFIX, and transduced with retrovirus MFG-hFIX. Two human primary myoblast clones secreting approximately 1 microg hFIX/10(6) cells/day were enclosed in biocompatible alginate microcapsules and implanted intraperitoneally into SCID and hemophilic mice. RESULTS: Circulating hFIX (peak of approximately 120 ng/ml) was detected in hemophilia B mice on day 1 after implantation. Human FIX delivery was transient, however, becoming undetectable on day 14. Concurrently, anti-hFIX antibodies were detected. At the same time, activated partial thromboplastin time (APTT) was reduced from 94 s before treatment to 78-80 s. Tail bleeding time decreased from 15 min to 1.5-7 min after treatment, some mice being normalised. These findings indicate that the delivered hFIX is biologically active. Similarly treated NOD/SCID mice had circulating hFIX levels of 170 ng/ml on day 1 that remained detectable for 1 month, albeit at low levels. Cell viability of microcapsules retrieved on day 60 was below 5%. CONCLUSIONS: Our findings indicate that encapsulated human primary myoblasts secrete functional hFIX. Furthermore, implantation of encapsulated human primary myoblasts can partially correct the phenotype of hemophilia B mice, supporting the feasibility of this gene therapy approach for hemophilia B. However, the long-term viability of the encapsulated human myoblasts must first be improved. PMID- 17868188 TI - A functional analysis of KlSRB10: implications in Kluyveromyces lactis transcriptional regulation. AB - The function of KlSRB10 has been studied by diverse approaches. Primer extension analysis reveals several transcription start sites, position - 17 from ATG being predominant. Deletion of KlSRB10 diminishes growth in ethanol and decreases KlCYC1 transcript levels. A second phenotype associated with this deletion affects growth in galactose. These phenotypes are independent of the specific sequence connecting the ATP binding cassette and the kinase domain of Srb10p in yeasts. KlSrb10p is not necessary for LAC4 repression mediated by KlGal80p, as deduced by construction of a Klgal80Deltasrb10Delta double mutant. In the two hybrid system, KlSrbp10p interacts with the protein encoded by KLLA0E08151g (KlSrbp11p). PMID- 17868189 TI - Modelling dynamic processes in yeast. AB - Yeast molecular and cell biology has accumulated large amounts of qualitative and quantitative data of diverse cellular processes. The results are often summarized as verbal or graphical descriptions. Moreover, a series of mathematical models has been developed that should help to interpret such data, to integrate them into a coherent picture and to allow for an understanding of the underlying processes. Dynamic modelling of regulatory processes in yeast focuses on central carbon metabolism, on a number of selected signalling pathways and on cell cycle regulation. These models can explain questions of general relevance, such as whether the dynamics of a network can be understood from the combination of in vitro kinetics of its individual reactions. They help to elucidate complicated dynamic features, such as glycolytic oscillations, effects of feedback regulation or the optimal regulation of gene expression. The availability of comprehensive qualitative information, such as protein interactions or pathway composition, and sets of quantitative data make yeast a perfect model organism. Therefore, yeast related data are often used to develop and examine computational approaches and modelling methods. PMID- 17868191 TI - Role of CYP2C9 and CYP2C19 polymorphisms in patients with atherosclerosis. AB - The arachidonic acid metabolizing CYP enzymes with prominent roles in vascular regulation are epoxygenases of the two gene family which generate epoxyeicosatrienoic acids. Carriers of CYP2C9 mutant alleles exhibit a diminished CYP2C9 metabolic capacity leading to decreased endothelium-derived hyperpolarizing factors (EDHF) synthesis and an increased risk for atherosclerosis. We investigated whether the polymorphisms of CYP2C9/19 are related with atherosclerosis. We examined 108 patients having angioraphically > or =70 coronary artery narrowing and 90 healthy controls. CYPC2C9/19*2 and CYP2C9/19*3 alleles were investigated in both patients and controls by a real time PCR instrument. There was no significant difference in the distribution of the CYP2C9*2/*3 alleles between cases and the controls. We found that smoker patients having CYP2C9*2 heterozygote genotype have 3.7-fold risk of developing atherosclerosis. CYP2C19*3 heterozygote alleles are more frequent in patients than in controls (10.2%, 5.6% respectively) and it is related with a three-fold risk of atherosclerosis (odds ratio (OR) = 3.75, confidence interval (CI) = 0.75 18.65). It becomes clear that cigarette smoking can cause almost all major diseases prevalent today, such as cancer or heart disease. This inter-subject variability in cigarette-induced pathologies is partly mediated by genetic variants of genes that may participate in detoxification processes, e.g., cytochrome P450 (CYP), cellular susceptibility to toxins, such as p53, or disease development such as atherosclerosis. PMID- 17868190 TI - R-CHOP-14 in patients with diffuse large B-cell lymphoma younger than 70 years: a multicentre, prospective study. AB - Several studies have shown that adding rituximab to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) or reducing the interval between chemotherapy cycles from 3 weeks to 2 weeks improves survival in patients with diffuse large B-cell lymphoma (DLBCL). These studies prompted our group (GOTEL) to evaluate prospectively in a pilot study the feasibility and efficacy of R-CHOP 14 in patients with DLBCL. Patients (<70 years) with stage II bulky or stage III or IV DLBCL and no significant comorbidities were included in the study. Rituximab was administered on day 1 before chemotherapy. R-CHOP was given every 14 days. All patients received filgrastim (5 microg/kg) from days 4 to 10. From May 2002 to August 2004, 80 patients were recruited. Median age was 53 years and 58 patients were <60 years. According to the age-adjusted international prognostic index (aaIPI), 13 patients (16%) had low-risk disease, 31 (39%) low-to intermediate risk, 27 (34%) high-to-intermediate risk and 9 (11%) high-risk disease. Grade 3-4 neutropenia was observed in 15 patients (17.5%) and grade 3-4 infections in 13 patients (16%). After therapy, 58 patients (73%) achieved CR-CRu (95% CI: 55-90%). With a median follow-up of 26 months, progression-free survival (PFS) and overall survival (OS) at 30 months were 72% and 86%, respectively. Administration of R-CHOP-14 is feasible and effective in patients <70 years. PMID- 17868193 TI - Drug prescribing pattern at the medical outpatient clinic of a tertiary hospital in southwestern Nigeria. AB - PURPOSE: Assessment of drug use patterns with World Health Organization (WHO) Drug Use Indicators is becoming increasingly necessary towards promoting rational drug use in the developing countries. This study aimed at assessing the drug prescription pattern at the Medical Outpatient Clinic (MOP), University College Hospital, Ibadan, using some WHO core drug use indicators. METHODS: One thousand four hundred and forty-seven patient encounters were reviewed prospectively over a 2-month period. Data were collected from patient case files immediately following consultation in each of the seven subspecialty clinics at the MOP. Prescribed medications were then reviewed for some drug use indicators including cost of medications. Cost was based on the current hospital pharmacy drug-pricing list. RESULTS: One thousand three hundred and seven (90.3%) prescriptions from 1447 patient encounters were reviewed. One hundred and forty (9.7%) encounters did not have prescriptions written out. The overall average number of drugs prescribed was 3.2 +/- 1.47. Average percentage of drugs prescribed by generic names was 49.5% +/- 31.2, while average percentage of drugs prescribed from the hospital essential drug list was 96% +/- 14.0. The average cost of medications to patients/day was N = 126.0 +/- 136.0 approximately $0.9 (USD). Results varied between subspecialties. CONCLUSION: The low percentage prescription of drugs by their generic name is responsible for the high cost of drugs to patients. Drug use studies are a necessary tool for assessing prescribing patterns in hospitals, recognizing areas for improvement and improving drug prescribing practices in these facilities. PMID- 17868192 TI - Artemin activates axonal growth via SFK and ERK-dependent signalling pathways in mature dorsal root ganglia neurons. AB - Artemin, one of the glial cell line-derived neurotrophic factor (GDNF) family, enhances the generation and survival of early sympathetic neurons and superior cervical ganglion (SCG) neurons. Src-family kinases (SFK) are involved in the growth and differentiation of cells, which are composed of unique Src homology 2 (SH2), Src homology 3 (SH3) and kinase domains. Various extra-cellular molecules containing growth factors and G-protein coupled receptors stimulate SFK. In this report, artemin is shown to have a significant effect on the neurite growth of dorsal root ganglia (DRG) neurons. Also, artemin triggers Src-family kinase activation and the phosphorylation of extra-cellular signal-regulated kinases (ERK) mitogen-activated protein kinase (MAPK). Artemin also regulated actin polymerization. There are several indications that another SH3-containing protein, Hck, and an SH3-containing adaptor protein, Nck1, play an important role in the organization of the actin cytoskeleton by cellular signalling. These findings suggest that the exploration of binding partners for the SH3 domain could provide an insight into regulation between the microtubule and actin networks. The binding partners for the SH3 domains of Nck, Src and Hck that we identified were Smc chromosome segregation ATPases, FOG Zn-finger protein and the FYVE zinc-binding domain, respectively. PMID- 17868194 TI - Loudness dependence of evoked dipole source activity during acute serotonin challenge in females. AB - OBJECTIVES: Direct challenge of cortical serotonergic (5-hydroxytryptamine, 5-HT) availability by tryptophan depletion test (TDT) was used to assess the hypothesized inverse relationship between central 5-HT function and loudness dependence of auditory evoked potentials (LDAEPs). Gender must be taken into particular account here, since there are gender differences in 5-HT brain synthesis, with women reacting more strongly to TDT. METHODS: In a double-blind, controlled cross-over study, 16 healthy females were ingested two highly concentrated amino acid mixtures with (+TRP) or without TRP (-TRP). While monitoring TRP levels and mood states, the AEP of different loudness stimuli were recorded, followed by dipole source analysis. RESULTS: Under the -TRP condition, free plasma TRP levels decreased by 81.10% (+/-5.14). Most of the loudness change rates of the relevant N1/P2 tangential dipole activities were significantly increased under -TRP, but calculated LDAEP did not differ significantly between treatments. LDAEP and states of mood were not correlated. CONCLUSIONS: Despite strong TRP depletion, the results did not reach sufficient evidence that LDAEP is a valid biological marker of central 5-HT activity in females when using TDT. This agrees with the literature and supports the view that LDAEP indicates predominantly biological vulnerability in predisposed individuals. PMID- 17868195 TI - Modafinil and nicotine interactions in abstinent smokers. AB - In this study, we examined the effects of a wakefulness-promoting medication, modafinil, alone and with the nicotine lozenge, on subjective, physiological and cognitive measures as well as on nicotine withdrawal in overnight abstinent cigarette smokers. Nineteen smokers, 13 male and 6 female, participated in a double-blind, placebo-controlled, crossover study. In each of three experimental sessions, subjects were treated orally with a single 200 mg or 400 mg dose of modafinil or placebo. Two hours and 10 min following the medication treatment, subjects received a single 2 mg nicotine lozenge. Both doses of modafinil alone increased the rating of elated-depressed on the Profile of Mood States (POMS) subscale in the direction of depressed and increased ratings of negative affect on the Positive and Negative Affect Schedule (PANAS). In contrast, the 200 mg modafinil dose combined with a 2 mg nicotine lozenge, increased the rating of energetic-tired in the direction of energetic on the POMS subscale. Modafinil attenuated self-reported rating of 'drug strength' in response to the nicotine lozenge. Modafinil, alone or in combination with the nicotine lozenge, did not affect tobacco withdrawal symptoms. There was an increase in baseline heart rate and systolic blood pressure under modafinil treatment. In addition, modafinil speeded reaction times on a modified Stroop task. The clinical utility of modafinil for smoking cessation needs to be determined in future studies. PMID- 17868196 TI - Protective effects of melatonin and N-acetylserotonin on aflatoxin B1-induced lipid peroxidation in rats. AB - Aflatoxin B1 (AFB1) is a potent hepatotoxic and hepatocarcinogenic mycotoxin. Reactive oxygen species are considered to participate in the main mechanism of aflatoxin toxicity. Melatonin (Mel) is a hormone which has antioxidative activities. N-acetylserotonin (NAc-5HT) is an immediate precursor of Mel. Melatonin is documented to be completely safe in humans and animals. The aim of our study was to examine the potential protective effects of Mel or NAc-5HT against lipid peroxidation (LPO), caused by AFB1 in male Wistar rats. Mel and NAc 5HT were intraperitoneally (i.p.) injected for 3 weeks in late afternoon (16:00 18:00) injections (20 mg kg(-1) BW/daily). AFB1 (50 microg kg(-1) BW/daily) was administered i.p. 6 h prior to indoleamine injections. Concentrations of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA), as an index of LPO, were measured in liver, brain, lung, testis and kidney homogenates. The level of LPO in tissue homogenates was expressed as the amount of MDA + 4-HDA (nmol) per milligram of protein. AFB1 increased LPO in the liver, lung, brain and testis, but not the kidney. The increase of LPO caused by AFB1 injections was completely prevented by either Mel or NAc-5HT in all the tissues examined. Melatonin can be considered as a protective pharmacological agent in intoxication with AFB1 and the protective effect of NAc-5HT against aflatoxin-induced LPO broadens the knowledge about its antioxidative properties. PMID- 17868197 TI - Retrospective database analysis on the effectiveness of typical and atypical antipsychotic drugs in an outpatient clinic setting. AB - OBJECTIVE: To report the outcomes of a retrospective database analysis to compare the effectiveness of atypical and typical antipsychotic drugs. METHODS: Medical records of patients admitted to the psychiatry outpatient clinic between January 1998 and October 2005 were retrospectively reviewed. Data obtained from patient records were noted on a special form assessing four aspects of the treatment history: socio-demographic features, disease characteristics, initial treatment at the time of admission, and course of treatment. Patient groups (typical/atypical and Risperidone/Haloperidol/Olanzapine) were compared for time to all-cause medication discontinuation and rate of discontinuation. RESULTS: There was no statistically significant difference in the duration of treatment between patients using atypical (n = 150) and typical (n = 124) antipsychotics. The duration of treatment was significantly longer in patients on Haloperidol (n = 91) compared with those on Risperidone (n = 63). Rates of discontinuation over 18 months were 59.3% for patients on atypical antipsychotics and 57.3% for those on typical antipsychotics, and 68.3% for patients on Risperidone, 51.6% for patients on Haloperidol and 54.3% for patients on Olanzapine. CONCLUSION: Despite our hypothesis patients with chronic schizophrenia discontinued their atypical and typical antipsychotics, at a high rate with no significant difference indicating substantial limitations in the effectiveness of these drugs. PMID- 17868199 TI - Pharmacological and clinical evidences on the potential for abuse and dependence of propofol: a review of the literature. AB - Propofol (2,6-diisopropylphenol) is an intravenous short-acting anaesthetic widely used for inducing and maintaining anaesthesia. Propofol is also being increasingly used for sedation. Beside medical use, propofol is abused for recreational purpose, mostly in medical professionals who are not informed of the risk of dependence to this compound. The aim of this review was to provide an overview of molecular, animal and clinical pharmacological data of the literature evidencing the potential for abuse and dependence of propofol. PMID- 17868200 TI - Amine oxidases and monooxygenases in the in vivo metabolism of xenobiotic amines in humans: has the involvement of amine oxidases been neglected? AB - In this review, the major enzyme systems involved in vivo in the oxidative metabolism of xenobiotic amines in humans are discussed, i.e. the monooxygenases [cytochrome P450 system (CYPs) and flavin-containing monooxygenases (FMOs)] and the amine oxidases (AOs). Concerning the metabolism of xenobiotic amines (drugs in particular) by monoamine oxidases (MAOs), this aspect has been largely neglected in the past. An exception is the extensive investigation carried out on the inhibition of the metabolism of tyramine, when tyramine-containing food is ingested by subjects taking inhibitors of MAO A or of both MAO A and B. Moreover, investigations in humans on the metabolism of drug amines on the market by AOs, such as semicarbazide-sensitive amine oxidases (SSAOs) and polyamine oxidases (PAOs), are practically nonexistent, with the exception of amlodipine. In contrast to MAOs, monooxygenases (CYP isoenzymes more than FMOs) have been extensively investigated concerning their involvement in the metabolism of xenobiotics. It is possible that the contribution of AOs to the overall metabolism of xenobiotic amines in humans is underestimated or erroneously estimated, as most investigations of drug metabolism are performed using in vitro test systems optimized for CYP activity, such as liver microsomes, and most investigations of drug metabolism in vivo in humans carry out only the identification of the final, stable metabolites. However, for some drugs on the market, the involvement of MAOs in their in vivo metabolism in humans has been demonstrated recently, among these drugs citalopram, sertraline and the triptans are examples that can be mentioned. PMID- 17868201 TI - Empirical mode decomposition to assess cardiovascular autonomic control in rats. AB - Heart beat rate and blood pressure, together with baroreflex sensitivity, have become important tools in assessing cardiac autonomic system control and in studying sympathovagal balance. These analyses are usually performed thanks to spectral indices computed from standard spectral analysis techniques. However, standard spectral analysis and its corresponding rigid band-pass filter formulation suffer from two major drawbacks. It can be significantly distorted by non-stationarity issues and it proves unable to adjust to natural intra- and inter-individual variability. Empirical mode decomposition (EMD), a tool recently introduced in the literature, provides us with a signal-adaptive decomposition that proves useful for the analysis of non-stationary data and shows a strong capability to precisely adjust to the spectral content of the analyzed data. It is based on the concept that any complicated set of data can be decomposed into a finite number of components, called intrinsic mode functions, associated with different spectral contributions. The aims of this study were twofold. First, we studied the changes in the sympathovagal balance induced by various pharmacological blockades (phentolamine, atropine and atenolol) of the autonomic nervous system in normotensive rats. Secondly, we assessed the use of EMD for the analysis of the cardiac sympathovagal balance after pharmacological injections. For this, we developed a new (EMD-based) low frequency vs. high frequency spectral decomposition of heart beat variability and systolic blood pressure, we define the corresponding EMD spectral indices and study their relevance to detect and analyze changes accurately in the sympathovagal balance without having recourse to any a priori fixed high-pass/low-pass filters. PMID- 17868202 TI - Pharmacological evidence of calcium-channel blockade by essential oil of Ocimum gratissimum and its main constituent, eugenol, in isolated aortic rings from DOCA salt hypertensive rats. AB - Intravenous (i.v.) treatment of conscious DOCA-salt hypertensive rats with the essential oil of Ocimum gratissimum L. (Labiatae) (EOOG) induced a hypotensive effect that seems related to an active vascular relaxation rather than withdrawal of sympathetic tone. To corroborate this hypothesis, the present study examined the vascular effects of EOOG and its main constituent, eugenol (EUG) and the putative mechanisms underlying these effects. Additionally, the role of the vascular beta(2)-adrenergic mechanism in the mediation of EOOG-induced hypotension has also been investigated. In conscious DOCA-salt hypertensive rats, the EOOG-induced hypotension was reversible and remained unchanged by i.v. pretreatment with propranolol (2 mg/kg). In isolated aorta preparations with intact endothelium from DOCA-salt hypertensive rats, EOOG (1-1000 microg/mL) and EUG (0.006-6 mM) relaxed the phenylephrine-induced contraction similarly with IC(50) [geometric mean (95% confidence interval)] values of 226.9 (147.8-348.3) microg/mL and 1.2 (0.6-2.1) mm, respectively. Vasorelaxant effects of EOOG were significantly altered by removal of the vascular endothelium [IC(50) = 417.2 (349.5-497.8) microg/mL]. In a calcium-free medium, the CaCl(2)-induced contractions were significantly reduced and even abolished by EOOG at 300 and 1000 microg/mL, respectively, whereas EOOG (1000 microg/mL) did not have any significant effect on caffeine-induced contractions. Similar results were obtained with EUG (1.8 and 6 mM) on both CaCl(2)- and caffeine-induced contractions, respectively. The data suggest that hypotensive responses to EOOG in DOCA-salt hypertensive rats are due to an active vascular relaxation, which is partly dependent upon the integrity of the vascular endothelium and seems predominantly mediated through an inhibition of plasmalemmal Ca(2+) influx rather than Ca(2+)-induced Ca(2+) release from the sarcoplasmic reticulum. PMID- 17868203 TI - Inhibitory effect of Hemidesmus indicus and its active principle 2-hydroxy 4 methoxy benzoic acid on ethanol-induced liver injury. AB - The study evaluates the inhibitory activity of ethanolic root extract of Hemidesmus indicus (H. indicus) and its active principle 2-hydroxy 4-methoxy benzoic acid (HMBA) on liver fibrotic markers and characteristics such as collagen content, matrix metalloproteinases (MMPs) 2 and 9 in ethanol-fed rats. Experimental groups were control, H. indicus (500 mg/kg body weight every day during the last 30 days), HMBA (200 microg/kg body weight every day during the last 30 days), alcohol (5 g/kg body weight by intragastric intubation everyday, i.e. throughout the experimental period of 60 days), alcohol plus H. indicus and alcohol plus HMBA. Ethanol administration significantly increased the levels of liver collagen and hydroxy proline content, cross-linked fluorescence, shrinkage temperature and lipid peroxidation and significantly decreased the solubility of liver collagen and the ascorbic acid content when compared with control rats. On treatment with H. indicus and HMBA the ethanol-fed rats showed significantly reduced levels of liver collagen and hydroxyproline content, cross-linked fluorescence, shrinkage temperature and lipid peroxidation and enhanced solubility of liver collagen and ascorbic acid levels when compared with untreated ethanol-fed rats. MMPs were extracted from the liver of control, H. indicus-treated, HMBA-treated, ethanol-administered, ethanol with H. indicus coadministered and ethanol with HMBA-coadministered rats. The inhibition was analyzed by gelatin zymography and the percentage of expression was determined by a gel documentation system. The activities of MMPs 2 and 9 were significantly increased in ethanol-supplemented rats. Cotreatment of H. indicus/HMBA with ethanol showed significantly decreased activities of these enzymes when compared with those of the untreated rats. H. indicus/HMBA alone treatment showed no such significant alterations. Thus, our present study reveals the strong inhibitory activity of H. indicus and HMBA on the quantitative and qualitative properties of hepatic collagen and also MMPs involved in the extracellular matrix degradation during ethanol intoxication. PMID- 17868204 TI - Synergistic interaction between dexamethasone and tramadol in a murine model of acute visceral pain. AB - Tramadol is effective in the management of mild to moderate postoperative pain, but its administration is associated with nausea and vomiting. Patients treated with tramadol, often receive dexamethasone as antiemetic. The aim of our investigation was to assess if the two drugs interact in a murine model of acute visceral pain. Using the acetic acid writhing test in mice, we assessed the antinociceptive effects of tramadol and dexamethasone (a glucocorticoid with antiemetic effect) administrated individually and in a 1 : 1 fixed ratio combination. Tramadol and dexamethasone induced a dose-dependent inhibition of the writhing response when administered individually, with ED(50) values of 2.9 [2.09-4.31, 95% confidence limit (CL)] mg/kg, and 0.13 (0.05-0.29, 95% CL) mg/kg, respectively. The ED(50) of the combination was 0.13 (0.01-0.29, 95% CL) mg/kg; the isobolographic and interaction index analysis revealed a synergistic interaction. The results suggest that the combination of tramadol and dexamethasone could be beneficial in the management of postoperative pain in humans. PMID- 17868205 TI - Protective effect of rutin, a polyphenolic flavonoid against haloperidol-induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes. AB - The occurrence and irreversibility of tardive dyskinesia (TD), a motor disorder of the orofacial region, resulting from chronic neuroleptic treatment has been considered a major clinical issue in the treatment of schizophrenia. The molecular mechanism underlying the pathophysiology of TD is not completely known. Several animal studies have demonstrated an enhancement of oxidative damage and increased glutamatergic transmission after chronic administration of neuroleptics. The present study investigated the effect of rutin, an antioxidant in haloperidol-induced orofacial dyskinesia by using different behavioural (orofacial dyskinetic movements, stereotypic rearing, locomotor activity, percent retention), biochemical [lipid peroxidation, reduced glutathione levels, antioxidant enzyme levels (SOD and catalase)] and neurochemical (neurotransmitter levels) parameters. Chronic administration of haloperidol (1 mg/kg i.p. for 21 days) significantly increased vacuous chewing movements, tongue protrusions and facial jerking in rats, which were significantly inhibited by rutin. Chronic administration of haloperidol also resulted in dopamine receptor sensitivity as evident by a well-shaped response (initial decrease followed by increase) in locomotor activity and stereotypic rearing and also decreased percent retention time on elevated plus maze paradigm. Pretreatment with rutin reversed these behavioural changes. Besides, haloperidol also induced oxidative damage in all regions of brain which was prevented by rutin, especially in the subcortical region containing striatum. Although turnover of dopamine and noradrenaline decreased in both cortical and subcortical regions after chronic administration of haloperidol, it was significantly reversed by high-dose rutin treatment. The findings of the present study suggested the involvement of free radicals in the development of neuroleptic-induced orofacial dyskinesia, a putative model of TD, and rutin as a possible therapeutic option to treat this hyperkinetic movement disorder. PMID- 17868206 TI - Effect of chronic chromium picolinate in animal models of anxiety and memory. AB - Diabetes mellitus is associated with certain neurological problems such as depression, anxiety, memory impairment, etc. As chromium picolinate (CrP), a widely used trace element is shown to have beneficial effects in diabetes and depression, we investigated its effects on elevated plus maze and spontaneous alternation behavior paradigm as a measure of anxiety and memory, respectively. CrP (8 microg/mL in drinking water) significantly increased percentage preference to open arm in elevated plus maze in diabetic and normal rats. However, no significant changes were observed in percentage alternation after CrP chronic treatment. The possible anxiolytic effect of CrP might be related to its effect on serotonergic transmission. PMID- 17868207 TI - Antioxidant properties of hesperidin in nicotine-induced lung toxicity. AB - Nicotine, the principal alkaloid in tobacco, is generally considered to be an active pharmacological agent responsible for lung-related disorders. The actions of nicotine have been extensively investigated in animal and variety of cell systems. Nicotine is known to induce the lipid peroxidation by producing reactive oxygen species and reactive nitrogen species. In the present study, we have investigated the effect of hesperidin on nicotine toxicity. The parameters studied were marker enzymes and antioxidant status in blood, tissues, BAL (bronchoalveolar lavage cells) and BALF (bronchoalveolar lavage fluid). Lung damage was induced by subcutaneous injection of nicotine at a dosage of 2.5 mg/kg body weight for 5 days a week. Hesperidin was administered orally at a dose of 25 mg/kg body weight. The results showed an increase in the level of marker enzymes and decrease in the antioxidant status in nicotine-treated rats. Hesperidin treatment resulted in a decreased level of all the marker enzymes and the antioxidant status was brought back to near normal. Thus the study shows that hesperidin offers protection against the lung damage caused by nicotine. PMID- 17868208 TI - The ameliorative effect of cysteine prodrug L-2-oxothiazolidine-4-carboxylic acid on cisplatin-induced nephrotoxicity in rats. AB - Pathogenesis of nephrotoxicity of the synthetic anticancer drug cisplatin (CP) involves generation of reactive oxygen species and free radicals in the kidney cortex, and cysteine prodrug l-2-oxothiazolidine-4-carboxylic acid (OTC) has been confirmed to have a strong antioxidant action. Therefore, in the present work, we aimed at testing the possible protective or palliative effect of OTC on CP nephrotoxicity in rats. OTC was given at an oral dose of 150 mg/kg/day for 7 days. On day 7, some of these rats were given a single intraperitoneal injection of CP (or vehicle) at a dose of 6 mg/kg. Rats were killed, blood and urine samples were collected, and the kidneys were removed 6 days after CP treatment. Nephrotoxicity was evaluated histopathologically by light microscopy, and biochemically by measuring the concentrations of creatinine and urea in serum, reduced glutathione (GSH) concentration and superoxide dismutase (SOD) activity in renal cortex, and by urinalyses. CP significantly increased the concentrations of urea and creatinine (P < 0.05) by about 128% and 170% respectively. CP treatment reduced cortical GSH concentration by about 34% (P < 0.05), and the activity of SOD by about 28% (P < 0.05). CP treatment significantly increased urine volume and N-acetyl-beta-D-glucosaminidase (NAG) activity, and significantly decreased osmolality and protein concentrations. OTC significantly mitigated all these effects. Sections from saline- and OTC-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This appeared to be lessened when CP was given simultaneously with OTC. The concentration of CP in the cortical tissues was not significantly altered by OTC treatment. The results suggested that OTC had ameliorated the histopathological and biochemical indices of nephrotoxicity in rats. Pending further pharmacological and toxicological studies, OTC may potentially be useful as a nephroprotective agent. PMID- 17868209 TI - Overview of adverse reactions to nefopam: an analysis of the French Pharmacovigilance database. AB - Nefopam is widely used for the relief of moderate acute pain. Its safety profile remains to be specified. The objective of the study was to review adverse reactions to nefopam spontaneously reported to the French Pharmacovigilance system. All cases of adverse drug reactions (ADRs) associated with nefopam, registered in the French Pharmacovigilance database from January 1, 1995 to December 31, 2004, were reviewed. For each reported ADR, information about patient (age, gender, medical history), drug exposure (suspected and concomitantly used drugs), characteristics of ADRs (imputability score, time of onset, seriousness, outcome) were collected. A total of 114 ADRs with an imputability rated from 'plausible' (I2) to 'likely' (I3) and 'very likely' (I4) was analysed. The most frequent ADRs included 'expected' ADRs such as sweating, nausea, tachycardia, malaise or vomiting; 61 ADRs were 'unexpected. No overdose was reported; 26 ADRs (23%) were considered as 'serious'. Most of them were 'unexpected', including neuropsychiatric (hallucinations, convulsions) or cutaneous (pruritus, erythema, urticaria) ADRs. Six cases of anaphylactic ADRs (two angioedema and four anaphylactic shocks) were reported, all occurring shortly after use of nefopam during the post-operative period. Physicians should be aware of the possible occurrence of some serious ADRs when using nefopam such as convulsions and anaphylactic shocks, especially when the drug is used in special medical conditions, like post-operative periods. PMID- 17868210 TI - The possible prophylactic effect of Nigella sativa seed extract in asthmatic patients. AB - In previous studies, the relaxant, anticholinergic (functional antagonism) antihistaminic, effects of Nigella sativa have been demonstrated on guinea-pig tracheal chains. In the present study, the prophylactic effect of boiled extract of N. sativa on asthmatic disease was examined. Twenty-nine asthmatic adults were randomly divided into control group (14 patients) and study group (15 patients), and they were studied for 3 months. In the study group 15 mL/kg of 0.1 g% boiled extract and in the control group a placebo solution was administrated daily throughout the study. Asthma symptom score, asthma severity, frequency of symptoms/week and wheezing were recorded in the beginning (first visit), 45 days after treatment (second visit), and at the end of the study (third visit). Pulmonary function tests (PFTs) were also measured, and the drug regimen of the patients was evaluated at three different visits. All asthma symptoms, frequency of asthma symptoms/week, chest wheezing, and PFT values in the study group significantly improved in the second and third visits compared with the first visit (P < 0.05 to P < 0.001). In addition, further improvement of chest wheezing and severity of disease on the third visit were observed compared with the second visit in this group (P < 0.05 for both cases). In the third visit all symptoms in the study group were significantly different from those of the control group (P < 0.01 to P < 0.001). However, in the control group, there were only small improvements in some parameters in just the second visit. The usage of inhaler and oral beta-agonists, oral corticosteroid, oral theophylline and even inhaler corticosteroid in the study group decreased at the end of the study while there were no obvious changes in usage of the drugs in control subjects. The results of phase I study generally suggest a prophylactic effect of N. sativa on asthma disease and warrant further research regarding this effect. PMID- 17868211 TI - Management of chronic hand eczema. AB - Hand eczema (HE) is one of the most frequent skin diseases and has often a chronically relapsing course with a poor prognosis resulting in a high social and economic impact for the individual and the society. In this article, we highlight the results of an expert workshop on the 'management of severe chronic hand eczema' with the focus on the epidemiology, the burden of severe HE, its classification and diagnostic procedures, and the current status of treatment options according to an evidence-based approach (randomized controlled clinical trials, RCTs). We conclude that despite the abundance of topical and systemic treatment options, disease management in patients with severe chronic HE is frequently inadequate. There is a strong need for RCTs of existing and new treatment options based on clearly diagnosed subtypes of HE and its severity. PMID- 17868212 TI - Incontinence in the aged: contact dermatitis and other cutaneous consequences. AB - Urinary and faecal incontinence affects a significant portion of the elderly population. The increase in the incidence of incontinence is not only dependent on age but also on the onset of concomitant ageing issues such as infection, polypharmacy, and decreased cognitive function. If incontinence is left untreated, a host of dermatological complications can occur, including incontinence dermatitis, dermatological infections, intertrigo, vulvar folliculitis, and pruritus ani. The presence of chronic incontinence can produce a vicious cycle of skin damage and inflammation because of the loss of cutaneous integrity. Minimizing skin damage caused by incontinence is dependent on successful control of excess hydration, maintenance of proper pH, minimization of interaction between urine and faeces, and prevention of secondary infection. Even though incontinence is common in the aged, it is not an inevitable consequence of ageing but a disorder that can and should be treated. Appropriate clinical management of incontinence can help seniors continue to lead vital active lives as well as avoid the cutaneous sequelae of incontinence. PMID- 17868213 TI - Patch testing with thin-layer chromatograms of chamomile tea in patients allergic to sesquiterpene lactones. AB - Patients with contact allergy to sesquiterpene lactones (SLs) are usually hypersensitive to Asteraceae plant products such as herbal teas. The objective of this study was to show sensitizers in chamomile tea by patch testing with thin layer chromatograms. Tea made from German chamomile was separated by thin-layer chromatography. Strips of the thin-layer chromatograms were used for patch testing SL-positive patients. 15 (43%) of 35 patients tested positively to 1 or more spots on the thin-layer chromatogram, with many individual reaction patterns. Patch testing with thin-layer chromatograms of German chamomile tea showed the presence of several allergens. PMID- 17868215 TI - Current patch test results in consecutive patients with, and chemical analysis of, disperse blue (DB) 106, DB 124, and the mix of DB 106 and 124. AB - Disperse blue (DB) 106 and 124 are important textile dye allergens. However, the dye raw material is impure, leading to uncertainty regarding the actual patch test (PT) concentration. To examine, (i) the allergen content of previously and currently used DB 106 and 124 and a respective mix, and (ii) the frequency of positive PT reactions to the DB 106/124 mix and to the single compounds in consecutive PT patients. High performance liquid chromatography (HPLC) analysis and purification of DB 106 and 124, respectively. Descriptive analysis of PT data from the Information network of departments of dermatology obtained between January 2003 and December 2005. Retrospectively, 2 batches of the DB 106/124 mix proved to contain an amount of allergen different to the 1 declared (based on information of suppliers of raw material). However, since February 2005, DB 106 and 124, respectively, are available at a reliable concentration of 0.3% petrolatum. In 2005, the prevalence of positive PT reactions to both the mix (0.89%) and the single constituents combined (0.56%) did not qualify them for inclusion in the standard series. Quality control, providing accurate test concentrations of allergens based on technical grade purity raw materials is necessary for valid diagnosis of contact allergy and comparable epidemiological data. PMID- 17868214 TI - Elicitation of contact hypersensitivity after repeated suberythemal exposures of humans to solar simulated radiation: number of epidermal Langerhans cells. AB - Ultraviolet radiation suppresses contact hypersensitivity (CHS). The role of epidermal Langerhans cells (LCs, CD1a(+)) in the elicitation phase of CHS is uncertain. To assess the effect of low-doses of solar simulated radiation (SSR) on LC numbers at the CHS elicitation site. 3 groups (each about 30 volunteers) were whole-body irradiated with suberythemal SSR on 2, 10 or 30 consecutive days before sensitization with diphenylcyclopropenone. Another group was not irradiated. Elicitation of CHS took place 3 weeks later with subsequent evaluation by visual scoring and spongiosis grade. CD1a(+) cells in the epidermis from the elicitation site were counted. No difference in CHS intensity between the unirradiated controls and all 3 irradiated groups was found, but a significant negative correlation between the spongiosis grade and the number of SSR exposures was shown. The number of epidermal CD1a(+) cells in the 10- and 30 day groups was reduced compared with the unirradiated group, and the 30-day group had significantly fewer than the 10-day group. Low daily doses of SSR induce suppression of CHS, leading to depletion of LCs at the CHS elicitation site. The effect on the CHS and LCs is cumulative, indicating that photoadaptation for these parameters does not develop over the 30 day irradiation period. PMID- 17868216 TI - Effects of disinfectants and detergents on skin irritation. AB - We investigated the biological response of regular human skin to alcohol-based disinfectants and detergents in a repetitive test design. Using non-invasive diagnostic tools such as transepidermal water loss, laser-Doppler flowmetry and corneometry, we quantified the irritative effects of a propanol-based hand disinfectant (Sterillium), its propanol mixture (2-propanol 45% w/w and 1 propanol 30% w/w), sodium lauryl sulfate (SLS) 0.5% and distilled water. The substances were applied in a 2-D patch test in a repetitive occlusive test design to the back. Additionally, we performed a wash test on the forearms that was supposed to mimic the skin affection in the normal daily routine of health care workers. In this controlled half-side test design, we included the single application of the hand rub, SLS 0.5% and water as well as a tandem application of the same substances. Patch test and wash test showed similar results. The alcohol-based test preparations showed minimal irritation rather comparable to the application of water. However, the detergent SLS produced stronger barrier disruption, erythema and dryness than the alcohol-based preparations. There was no additional irritation at the combined use of SLS and disinfectants. By contrary, there was even a decrease in barrier disruption and erythema induced by the tandem application of SLS followed by alcohol-based disinfection compared with the use of SLS alone. These findings show a less irritant effect of alcohol based disinfectants on the skin than detergents. Our study shows that there is no summation of irritating effects of a common detergent and propanol and that the combination of washing and disinfection has a rather protective aspect compared with washing alone. PMID- 17868217 TI - Comparative analysis of skin sensitization potency of acrylates (methyl acrylate, ethyl acrylate, butyl acrylate, and ethylhexyl acrylate) using the local lymph node assay. AB - There are currently available no systematic experimental data on the skin sensitizing properties of acrylates that are of relevance in occupational settings. Limited information from previous guinea-pig tests or from the local lymph node assay (LLNA) is available; however, these data are incomplete and somewhat contradictory. For those reasons, we have examined in the LLNA 4 acrylates: butyl acrylate (BA), ethyl acrylate (EA), methyl acrylate (MA), and ethylhexyl acrylate (EHA). The LLNA data indicated that all 4 compounds have some potential to cause skin sensitization. In addition, the relative potencies of these acrylates were measured by derivation from LLNA dose-response analyses of EC3 values (the effective concentration of chemical required to induce a threefold increase in proliferation of draining lymph node cells compared with control values). On the basis of 1 scheme for the categorization of skin sensitization potency, BA, EA, and MA were each classified as weak sensitizers. Using the same scheme, EHA was considered a moderate sensitizer. However, it must be emphasized that the EC3 value for this chemical of 9.7% is on the borderline between moderate (<10%) and weak (>10%) categories. Thus, the judicious view is that all 4 chemicals possess relatively weak skin sensitizing potential. PMID- 17868218 TI - Retesting with the TRUE Test in a population-based twin cohort with hand eczema - allergies and persistence in an 8-year follow-up study. AB - Population-based studies on contact allergy with retesting of individuals are infrequently performed. Variable degrees of persistence are reported when individuals with contact allergy are retested with years in between. The patch test results of 270 individuals tested in 2005-2006 are presented and the pattern and frequency of sensitization discussed. Persistence when compared with patch test results from 1997-1998 is reported. 270 twin individuals with and without hand eczema underwent patch testing with the TRUE Test((R)) (Mekos Laboratories AS, Hilleroed, Denmark) in 1997-1998 and again in 2005-2006 as part of a larger study. In 2005-2006, a total of 74 (27.4%) of the 270 individuals had at least 1 positive patch test and 20 (7.4%) of the 270 had 2. The frequency in men and women was 9/90 (10%) and 65/180 (36.1%), respectively. The frequency of contact allergy in individuals with and without hand eczema was 59/185 (31.3%) and 15/85 (17.6%), respectively. The most prevalent contact allergies were to nickel, thiomersal, and fragrance mix I. All together, 74% of the positive reactions were reproduced. The frequency of contact allergy in this population-based cohort with hand eczema was comparable with previous reports. Persistence of contact allergy after many years was confirmed. PMID- 17868219 TI - Skin exposure in geriatric care - a comparison between observation and self assessment of exposure. AB - The aim of this study was to compare observation and self-assessment of skin exposure to irritants during a working day in nursing in geriatric care. The study group consisted of 40 volunteers, 13 nurses, and 27 assistant nurses. Before the start of a working day, the participants completed a questionnaire regarding skin exposure to water, gloves, hand disinfection, and moisturizers. Observers subsequently used a hand-held computer to register the time and frequency of each exposure. The total mean skin exposure time was 96 min per working day, including glove use. The mean exposure time to water was 9 min per working day. A tendency to overestimate was found for all exposures. A strong correlation between self-reports and observations was found for hand disinfection and moisturizers, while a moderate correlation was found for gloves and number of water exposures and a weak correlation for total time of water exposure. Despite the differences between self-assessment and observation of the exposure, we consider the questionnaire to be useful for surveying skin exposure in nursing. Furthermore, the observations in this study suggest that nursing work in geriatric care may comprise limited exposure to water. PMID- 17868220 TI - Self-reported skin symptoms in metal workers. AB - Machinists and machine maintenance men working in the metal industry use metal working fluids capable of causing irritant and allergic contact dermatitis. The objectives of this study were to find out the frequency of skin symptoms in machinists and machine maintenance men (metal workers) and to compare the risk of their skin symptoms to that in office workers (controls). A total of 726 male metal workers and 84 controls answered a structured telephone questionnaire enquiring about work, atopy, skin symptoms, their impact on life, etc. The risk of skin symptoms compared with that in the controls was estimated using a logistic regression analysis. Of the metal workers, 20% reported recurring or prolonged dermatitis on their hands or forearms during the past 12 months. The hand or forearm dermatitis (HD) affected mostly the metal workers' mood and their activities at work. Recurring dermatitis elsewhere (DE) than in the hands and in connection with work was reported by 10%. The risk of HD was about twofold and the risk of DE was about fourfold compared with that in the controls. The HD of machinists may be severe and affect their ability to work. DE may have clinical significance in machinists. PMID- 17868221 TI - 10-year prevalence of contact allergy in the general population in Denmark estimated through the CE-DUR method. AB - The prevalence of contact allergy in the general population has traditionally been investigated through population-based epidemiological studies. A different approach is the combination of clinical epidemiological (CE) data and the World Health Organization-defined drug utilization research (DUR) method. The CE-DUR method was applied in Denmark to estimate the prevalence of contact allergy in the general population and compare it with the prevalence estimates from the Glostrup allergy studies. Contact allergy prevalence estimates ranging from very liberal ('worst case') to conservative ('best case') assumptions were based on patch test reading data in combination with an estimate of the number of persons eligible for patch testing each year based on sales data of the 'standard series'. The estimated 10-year prevalence of contact allergy ranged between 7.3% and 12.9% for adult Danes older than 18 years. The 10-year prevalence of contact allergy measured by CE-DUR was slightly lower than previous prevalence estimates from the Glostrup allergy studies. This could probably be explained by a decrease in nickel allergy. The CE-DUR approach holds the potential of being an efficient and easy monitoring method of contact allergy prevalence. PMID- 17868222 TI - Positive photocontact responses are not elicited to sunscreen ingredients exposed to UVA prior to application onto the skin. AB - Photocontact allergic reactions to sunscreen chemicals are investigated by photopatch testing. It has generally been assumed that for photocontact allergy to be shown, the putative pro-allergen must be in the skin at the time of ultraviolet A (UVA) exposure. However, this assumption has not, to our knowledge, been tested. The objective of this study was to determine whether positive photocontact responses can still be elicited when sunscreen chemicals are exposed to UVA prior to application onto the skin. 3 patients known to have positive photocontact reactions to a total of 6 sunscreen chemicals were studied. For conventional photopatch testing, patch test strips were applied onto the back and removed 1 D later, and the area was irradiated with UVA (5 J/cm(2)). For pre irradiated testing, patches were exposed to the same dose of UVA immediately before application onto the back and then removed 1 D later. Skin responses were visually assessed by a blinded investigator 1 and 2 D after patch test removal. The same photocontact responses of the same magnitude, as previously documented for each patient, were seen at each of the conventional UVA-exposed patch test sites. However, in no patient was a positive response elicited at any of the sites where pre-irradiated patches had been applied. This study shows that positive photocontact responses to sunscreen chemicals do not occur when the putative pro-allergen is irradiated prior to application onto the skin. This suggests that for a photoallergic reaction to occur, the sunscreen chemical needs to be within the skin when activated by UVA. PMID- 17868223 TI - Occupational allergic contact dermatitis caused by aerosols of acrylate monomers. PMID- 17868224 TI - Allergic contact dermatitis caused by tosylamide formaldehyde resin in nail varnish: an old allergen that has not disappeared. PMID- 17868225 TI - Allergic contact dermatitis to Aloe vera. AB - We present the case of a 72-year-old woman observed for dermatitis on the legs followed by apperance of erythema on the eyelids. She had a past history of peripheral venous insufficiency and had been using self home-made Aloe vera juice over the legs for relief from pain. Patch tests showed positive reactions to the leaf of Aloe, the macerated Aloe jelly, and nickel sulfate. Although most manufacturers process Aloe products avoiding its irritant extracts, and probably as a consequence reports of allergic reactions are rare, one must remember that the growing popularity on the use of Aloe products may stimulate its use 'as is' by the patients. Furthermore, it is important to specifically ask patients about the use of these products, because they consider it as innocuous and thus would not spontaneously provide such information. PMID- 17868226 TI - Contact dermatitis due to Allivum sativum and Ranunculus illyricus: two cases. AB - Plants are of relevance to dermatology for both their adverse and beneficial effects on skin and skin disorders respectively. Virtually all cultures worldwide have relied historically, or continue to rely on medicinal plants for medical care. As alternative herbal remedies are becoming more widely used there is an increase in phytocontact dermatitis. Here we document two patients who developed contact dermatitis due to Allivum sativum, and Ranunculus illyricus after applying to the skin in order to relieve the rheumatological joint pain. PMID- 17868227 TI - Onycholysis induced by nail hardener. AB - Nail hardeners appeared in the market during the 1960s. They were basically solutions of formaldehyde. The first adverse effects were published in 1966 (1). Reactions were onycholysis, chromonychia, subungual haemorrhage, and hyperkeratosis. Onycholysis may be non-inflammatory or inflammatory, and is accompanied by throbbing pain. Inflammatory reactions are followed by paronychia and occasional dermatitis on the digital pulpa. PMID- 17868228 TI - Allergic contact dermatitis to cod liver oil contained in a topical ointment. PMID- 17868229 TI - Simvastatin - occupational contact dermatitis. PMID- 17868230 TI - Contact dermatitis to hydrolyzed wheat protein. PMID- 17868231 TI - Occupational airborne contact dermatitis from saffron bulbs. PMID- 17868232 TI - Occupational contact urticaria due to pennyroyal (Mentha pulegium). PMID- 17868233 TI - Urban-rural flows of physicians. AB - CONTEXT: Physician supply is anticipated to fall short of national requirements over the next 20 years. Rural areas are likely to lose relatively more physicians. Policy makers must know how to anticipate what changes in distribution are likely to happen to better target policies. PURPOSE: To determine whether there was a significant flow of physicians from urban to rural areas in recent years when the overall supply of physicians has been considered in balance with needs. METHODS: Individual records from merged AMA Physician Masterfiles for 1981, 1986, 1991, 1996, 2001, and 2003 were used to track movements from urban to rural and rural to urban counties. Individual physician locations were tracked over 5-year intervals during the period 1981 to 2001, with an additional assessment for movements in 2001-2003. FINDINGS: Approximately 25% of physicians moved across county boundaries in any given 5-year period but the relative distribution of urban-rural supply remained relatively stable. One third of all physicians remained in the same urban or rural practice location for most of their professional careers. There was a small net movement of physicians from urban to rural areas from 1981 to 2003. CONCLUSIONS: The data show a net flow from urban to rural places, suggesting a geographic diffusion of physicians in response to economic forces. However, the small gain in rural areas may also be explained by programs that are intended to counter normal market pressures for urban concentrations of professionals. It is likely that in the face of an overall shortage, rural areas will lose physician supply relative to population. PMID- 17868234 TI - The experience of rural independent pharmacies with medicare part D: reports from the field. AB - CONTEXT: The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) created prescription drug coverage for Medicare beneficiaries through a new Part D program, the single largest addition to Medicare since its creation in 1965. Prior to program implementation in January 2006, concerns had been voiced as to how independent pharmacies, which represent a higher proportion of all retail pharmacies in rural areas, would fare under the new program. PURPOSE: This article describes first-hand reports from rural pharmacist-owners about their experiences with Medicare Part D plans in the first 7 months of 2006 in order to gain a more thorough understanding of the challenges faced by rural independent pharmacies as a result of program implementation. METHODS: A semi structured interview protocol was utilized in telephone interviews with 22 pharmacist-owners of rural independent pharmacies in 10 states. FINDINGS: The rural independent pharmacists interviewed are experiencing major changes in payment, administrative burden, and interaction with patients as a result of the shift of patients into Medicare Part D plans. While administrative burden has greatly increased, payment and clinical interaction have decreased. CONCLUSION: Actions should be considered that would help rural independent pharmacists adjust to the new circumstances of having Medicare patients mirror, for administrative and payment purposes, commercially insured patients. Long-term modification of existing policies and regulations may be necessary to assure reasonable access to pharmaceuticals for rural populations. Further study is needed to determine how best to target these modifications to essential pharmacies. PMID- 17868235 TI - Pharmacy access to emergency contraception in rural and frontier communities. AB - CONTEXT: Timely access to emergency contraception (EC) has emerged as a major public health effort in the prevention of unintended pregnancies. The recent FDA decision to allow over-the-counter availability of emergency contraception for adult women presents important rural health implications. American women, especially those living in rural and frontier areas, have one of the highest rates of unintended and teen pregnancy among developed countries. PURPOSE: This study, conducted prior to the recent FDA ruling, evaluated the participation among California pharmacies in the pharmacy access program in December 2005, specifically comparing rural/frontier and urban pharmacies. METHODS: The sample consisted of 862 California pharmacies, including 50 in rural/frontier areas, which were randomly selected and surveyed by telephone. FINDINGS: The results indicated that similar proportions of rural/frontier pharmacies and urban pharmacies provided direct pharmacy access services (28% vs 22%, P = 0.32). However, of the 13 rural/frontier counties included in the survey, eight (62%) had no emergency contraception pharmacies. The rural/frontier pharmacies that provided emergency contraception services tended to be small, independent pharmacies in the most remote areas of the state. Among rural/frontier pharmacies that did not participate in the program, the primary reasons included lack of training or demand for emergency contraception. Only one rural/frontier pharmacist cited moral or religious opposition to providing emergency contraception. CONCLUSIONS: In light of the current limited over-the-counter status of emergency contraception, the role of rural and frontier pharmacies in ensuring access to emergency contraception will increase in the future. PMID- 17868236 TI - Variations in financial performance among peer groups of critical access hospitals. AB - CONTEXT: Among the large number of hospitals with critical access hospital (CAH) designation, there is substantial variation in facility revenue as well as the number and types of services provided. If these variations have material effects on financial indicators, then performance comparisons among all CAHs are problematic. PURPOSE: To investigate whether indicators of financial performance and condition systematically vary among peer groups of CAHs. METHODS: Suggestions from CAH administrators, a literature review, expert panel advice, and statistical analysis were used to create peer groups based on whether a CAH: (1) had less than $5 million, $5-10 million, or over $10 million in net patient revenue; (2) was owned by a government entity; (3) provided long-term care; and (4) operated a provider-based Rural Health Clinic. FINDINGS: Significant differences in financial performance and condition exist among CAH peer groups. CONCLUSIONS: CAHs should ensure that they use appropriate peer comparators when assessing their financial performance and condition. If quality, outcome, safety and access are affected by financial performance and condition, it may also be important for research in these areas to control for peer group differences among CAHs. PMID- 17868237 TI - Starting a general surgery program at a small rural critical access hospital: a case study from southeastern Oregon. AB - CONTEXT: Surgical services are frequently unavailable in rural American communities. Therefore, rural residents often must travel long distances to receive surgical care. Rural hospitals commonly have difficulty providing surgical services despite potential economic benefits. PURPOSE: The purpose of this project was to identify the key challenges and describe the initial outcomes experienced by Harney District Hospital (HDH), a rural critical access facility in Oregon, as it develops a surgical program. Since few models exist, this information will be valuable for those considering offering surgical services in a rural setting. METHODS: This project employed a single case study design. Qualitative information was gathered from semi-structured interviews, a focus group, reviews of historical documents, and informal observations. Quantitative data sources included HDH financial and utilization records, US Census records, and economic and demographic statistics from the state of Oregon, Harney County, and the city of Burns. FINDINGS: HDH is learning that initiating a change such as expanding surgical services within an organization is a challenging process requiring collaboration among the administration, staff, and community. Preliminary findings indicate that the new surgical program has resulted in significant financial gains for the hospital. CONCLUSIONS: While starting a rural surgery program is a complex undertaking, there are benefits for the hospital. If a rural hospital is to be successful in this mission, collaboration and adaptability must be key components of the process. PMID- 17868238 TI - Rural, suburban, and urban variations in alcohol consumption in the United States: findings from the National Epidemiologic Survey on Alcohol and Related Conditions. AB - CONTEXT: Alcohol consumption is a major public health problem nationally, but little research has investigated drinking patterns by rurality of residence. PURPOSE: To describe the prevalence of abstinence, alcohol use disorders, and risky drinking in rural, suburban, and urban areas of the United States. METHODS: Analyses of the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were conducted to estimate prevalence rates for abstinence, a current alcohol use disorder, and exceeding recommended daily and weekly drinking limits. Logistic regression analyses were conducted to test for rural and urban versus suburban differences after adjusting for potential confounders. Additional analyses were stratified by Census Region. FINDINGS: Nationally, the odds of abstinence and, among drinkers, the odds of a current alcohol disorder and exceeding daily limits were higher in rural than suburban areas. Stratified analyses revealed differences in the associations between rurality of residence and drinking across Census Regions. Rural residents of the Northeast, Midwest, and South and urban residents of the Northeast had higher odds of abstinence than their suburban peers. Among drinkers, rural and urban residents of the Midwest had higher odds of a current alcohol disorder and exceeding daily limits; urban residents of the Midwest had higher odds of exceeding weekly limits. CONCLUSIONS: Abstinence is particularly common in the rural South, whereas alcohol disorders and excessive drinking are more problematic in the urban and rural Midwest. Health policies and interventions should be further targeted toward those places with higher risks of problem drinking. PMID- 17868239 TI - Impact of a health promotion nurse intervention on disability and health care costs among elderly adults with heart conditions. AB - CONTEXT: Patients with heart conditions in rural areas may have different responses to health promotion-disease Self-management interventions compared to their urban counterparts. PURPOSE: To estimate the impact of a multi-component health promotion nurse intervention on physical function and total health care expenditures among elderly adults with heart conditions and to examine the impact of rural residence on the intervention effect. METHODS: We analyzed data on 281 community-living Medicare beneficiaries with heart conditions from the Medicare Primary and Consumer-Directed Care Demonstration (a randomized controlled trial). We estimated ordinary least squares (OLS) models to determine the effect of the intervention on the change in functional status and log-linear models to determine the impact of the intervention on total health care expenditures over a 2-year period. RESULTS: The OLS models showed that the nurse intervention resulted in fewer impairments in Activities of Daily Living (ADL) (-0.307 on 0-6 scale, P = .055) at the end of 2 years. The effect of the intervention on ADL appeared to be stronger for rural than for urban participants (-0.490 vs -0.162, respectively). However, the difference was not statistically significant (P = .150). The effect of the intervention on Instrumental Activities of Daily Living (IADL) was not significant (P = .321). Average total health care expenditures were 6.5% ($1,981, 95% CI: -$8,048, $4,087) lower in the nurse group. CONCLUSIONS: The nurse intervention led to better physical functioning and has potential to reduce total health care expenditures among high-risk Medicare beneficiaries with heart conditions. PMID- 17868240 TI - Ethnic and sex differences in ownership of preventive health equipment among rural older adults with diabetes. AB - CONTEXT: Diabetes self-management is important for achieving successful health outcomes. Different levels of self-management have been reported among various populations, though little is known about ownership of equipment that can enhance accomplishment of these tasks. PURPOSE: This study examined diabetes self management equipment ownership among rural older adults. METHODS: Participants included African American, American Indian, and white men and women 65 years of age and older. Data included equipment ownership overall and by ethnicity and sex across diabetes self-management domains (glucose monitoring, foot care, medication adherence, exercise, and diet). Associations between equipment ownership and demographic and health characteristics were assessed using logistic regression. FINDINGS: Equipment ownership ranged from 85.0% for blood glucose meters to less than 11% for special socks, modified dishes, and various forms of home exercise equipment. Equipment ownership was associated with ethnicity, living arrangements, mobility, poverty status, and formal education. CONCLUSIONS: Rural older adults with diabetes are at risk because they lack equipment to perform some self-management tasks. Providers should be sensitive to and assist patients in overcoming this barrier. PMID- 17868241 TI - Characteristics of crashes with farm equipment that increase potential for injury. AB - CONTEXT: Crash fatality and injury rates are higher on rural roadways than other roadway types. Although slow-moving farm vehicles and equipment are risk factors on rural roads, little is known about the characteristics of crashes with farm vehicles/equipment. PURPOSE: To describe crashes and injuries for the drivers of farm vehicles/equipment and non-farm vehicles involved in an injury crash. Passengers are not included in this analysis. METHODS: Injury crashes were included that involved a farm vehicle/equipment and at least one non-farm vehicle reported in Iowa Department of Transportation crash data from 1995 to 2004. Odds ratios were calculated through logistic regression to identify increased odds for injury among drivers of non-farm vehicles and farm vehicles/equipment. We examined frequently occurring crash characteristics to identify crash scenarios leading to the highest odds for injury. FINDINGS: Non-farm vehicle drivers were 5.23 times more likely to be injured than farm vehicle/equipment drivers (95% CI = 4.12-6.46). The absence of restraint use was a significant predictor of injury for both farm vehicle/equipment drivers (OR = 2.85; 95% CI = 1.14-7.13) and non farm vehicle drivers (OR = 2.53; 95% CI = 1.54-4.15). Crash characteristics increasing the odds of injury for non-farm vehicle drivers included speeding, passing the farm vehicle/equipment, driving on a county road, having a frontal impact collision, and crashing in darkness. Ejection was the strongest predictor of injury for the farm vehicle/equipment driver. CONCLUSION: Non-farm vehicle drivers were much more likely to be injured than farm vehicle/equipment drivers, suggesting that farm vehicle/equipment crash prevention should be a priority for all rural road users. Prevention strategies that reduce motor vehicle speed, assist in safe passing, increase seat belt use, and increase conspicuousness of the farm vehicle/equipment are suggested. PMID- 17868242 TI - Injury and illness costs in the Certified Safe Farm study. AB - CONTEXT: The Certified Safe Farm (CSF) intervention program aims to reduce occupational injuries and illnesses, and promote wellness to reduce health care and related costs to farmers, insurers, and other stakeholders. PURPOSE: To evaluate the cost effectiveness of CSF. METHODS: Farms (316) located in a 9 county area of northwestern Iowa were recruited and randomized into intervention and control cohorts. Intervention farms received occupational health screenings, health and wellness screening, education, on-farm safety reviews, and performance incentives. For both cohorts, quarterly calls over 3 years were used to collect self-reported occupational injury and illness information, including costs to the farmers and their insurers. FINDINGS: Annual occupational injury and illness costs per farmer paid by insurers were 45% lower in the intervention cohort ($183) than in the control cohort ($332). Although out-of-pocket expenses were similar for both cohorts, combined costs of insurance and out-of-pocket expenses were 27% lower in the intervention cohort ($374/year per farmer) compared to the control cohort ($512/year per farmer). Within the cohort of intervention farmers, annual occupational injury and illness cost savings were directly associated with on-farm safety review scores. Reported health care costs were $237 per farmer in the safest farms (those farms scoring in the highest tertile) versus $485 per farmer in the least safe farms (lowest tertile). CONCLUSIONS: Results suggest that farmers receiving the intervention had lower health care costs for occupational injuries and illnesses than control farmers. These cost savings more than cover the cost of providing CSF services (about $100 per farm per year). PMID- 17868243 TI - The impact of drought on the emotional well-being of children and adolescents in rural and remote New South Wales. AB - CONTEXT AND PURPOSE: Between 2002 and 2006 New South Wales was in the grip of the worst drought for more than 100 years. Financial hardships have led governments to declare "Exceptional Circumstances." Little social research has investigated the impact of drought on children. For this study, children from rural and remote regions of New South Wales were asked for their interpretations of the impacts of drought on their lives. METHODS: A multi-strategy approach combining qualitative and quantitative approaches was used to reveal deeper understanding of the impacts of drought. Students in Years 5 through 12 from six Central Schools in the rural southwest of New South Wales participated in focus groups and completed self-report questionnaires. RESULTS: Quantitative self-reports indicated these students were not significantly more distressed than Australian norms. However, the themes that emerged from the students' statements indicated that the drought had been a very significant event for them. This qualitative information also indicated connections for these students to their families, schools, and communities. CONCLUSIONS: The emotional impacts of changes to family and community life appear to have been moderated by these students' positive attitudes toward their country lifestyle. These students have discussed the impact of drought on their environment, their livestock, financial resources, and their families. In the face of declining rural community networks, children should be supported through programs that maintain resilience in the face of recurring environmental stressors. PMID- 17868245 TI - Emerging role of mitogen-activated protein kinases in peripheral neuropathies. AB - Among the different families of intracellular molecules that can be modulated during cell damage and repair, mitogen-activated protein kinases (MAPKs) are particularly interesting because they are involved in several intracellular pathways activated by injury and regeneration signals. Despite most of the studies have been performed in non-neurological models, recently a causal role for MAPKs has been postulated in central nervous system disorders. However, also in some peripheral neuropathies, MAPK changes can occur and these modifications might be relevant in the pathogenesis of the damage as well as during regeneration and repair. In this review, the current knowledge on the role of MAPKs in peripheral neuropathies will be discussed. PMID- 17868246 TI - Expression of metalloproteinases (MMP-2, MMP-9, and TACE) and TNF-alpha in the nerves of leprosy patients. AB - Matrix metalloproteinases (MMPs) and tumor necrosis factor alpha (TNF-alpha) play important and related roles in the pathogenesis of nerve injury. MMP-dependent and TNF-alpha-dependent processes of neurodegeneration, such as blood-nerve breakdown and immune cell recruitment, are characteristic of leprosy nerve damage. Our work has contributed to the understanding of the role of cytokines in the process, but the role of MMPs in the pathogenesis of neuritic leprosy has not been investigated. This study analyzed the changes in mRNA expression and immunodistribution of MMP-2, MMP-9, TNF-alpha-converting enzyme (TACE), TNF-alpha in nerves of 27 pure neuritic leprosy (PNL) patients, both acid-fast bacilli positive (AFB(+)) and acid-fast bacilli negative (AFB(-)), and 8 non-leprosy patients with control peripheral neuropathic conditions. MMP-2, MMP-9, and TNF alpha mRNA expression was significantly induced in the AFB(-) relative to the AFB(+) neuritic leprosy group and nonlepritic controls; TACE levels were also elevated in the AFB(-) group, but this change was not statistically significant. Immunoreactive profiles for TNF-alpha and MMPs demonstrated strong reactivity of myelinated axons, infiltrating macrophages, Schwann cells, endothelial cells, and perineurial cells in neuritic leprosy biopsies. This study provides the evidence of the involvement of MMPs in the pathogenesis of PNL neuropathy. PMID- 17868247 TI - Morphometric aspects of peripheral nerves in adults and the elderly. AB - There have been inconsistencies among reports of age-related differences in human peripheral nerves (PNs). For such studies, normal control values are necessary. Moreover, the diversity of methods employed makes it difficult to compare results. We used the same histological procedures and methods to measure 12 PNs: 8 in the cranial nerves, 2 motor nerves in the lower limb, and 2 nerves in the autonomic system. We performed a morphometric analysis of nerve fibers and estimated the change in the total number (TN) and average transverse area (ATA) of myelinated axons from adulthood to old age. The spinal nerves demonstrated notable age-related changes in TN and ATA. Most of the cranial nerves also demonstrated notable age-related changes in TN and ATA. However, some nerves demonstrated no such age-related changes and were affected more by other factors. With regards to the autonomic nerves, the lesser splanchnic nerve indicated age related changes in TN, but the greater splanchnic nerve indicated no age-related changes in either TN or ATA. The autonomic nerves were affected not only by the aging process but also by the pathological changes to the peripheral tissues that they innervate. PMID- 17868248 TI - The Total Neuropathy Score as an assessment tool for grading the course of chemotherapy-induced peripheral neurotoxicity: comparison with the National Cancer Institute-Common Toxicity Scale. AB - Chemotherapy-induced peripheral neurotoxicity (CIPN) is a major side effect of several antineoplastic drugs. However, despite its clinical importance, there is no agreement as to the best way to assess the severity and changes in CIPN. We have previously demonstrated a correlation between the severity of CIPN, assessed using the Total Neuropathy Score (TNS) or its reduced versions, and several common toxicity scales. In this study, we investigated two series of patients (total number = 173) who were evaluated at baseline and during chemotherapy with the TNS (n= 122) or the TNSc (the TNS version based exclusively on the clinical evaluation of the patients, n= 51) and with the National Cancer Institute-Common Toxicity Criteria (NCI-CTC) 2.0, with the aim of comparing the sensitivity to the changes in CIPN severity. In both series, the TNS and the TNSc had a significant correlation with the NCI-CTC in scoring the severity of CIPN, confirming the results of previous studies. Moreover, both the TNS and the TNSc showed a higher sensitivity to CIPN changes. We, therefore, propose the TNSc as a reliable method for assessing not only the severity but also the changes in CIPN. PMID- 17868249 TI - Two-dimensional digital video ankle motion analysis for assessment of function in the rat sciatic nerve model. AB - Ankle motion analysis may provide a better method to assess function in the rat sciatic nerve model than the standard method, the sciatic functional index (SFI), but it is not widely used in experiments on nerve regeneration possibly because of complicated analysis. In this study, we investigated the practical use of a two-dimensional (2D) digital video motion analysis system. Reproducibility was investigated in normal rats. Recovery of ankle motion was analyzed after sciatic, tibial, and peroneal nerve crush injury. Results were compared with scores for the SFI. Results were not significantly different from animal-to-animal and day to-day. Interobserver variability also was small. In the analysis of recovery after separate nerve crush injuries, subtle differences in ankle plantar flexion and dorsiflexion could be detected. The method was also more sensitive than the SFI: whereas scores for the SFI had returned to normal 4 weeks after sciatic nerve crush injury, the ankle angle at mid-stance was still significantly different from that in sham-operated animals 6 weeks after the injury. 2D digital video ankle motion analysis is a practical and sensitive method to assess function in the rat sciatic nerve model. PMID- 17868250 TI - Diagnostic role of deep tendon reflex latency measurement in small-fiber neuropathy. AB - Small-fiber neuropathy (SFN) is diagnosed on the basis of clinical features and specialized tests of small-fiber function because standard nerve conduction studies are normal. Thus, the objective of this study was to determine the value of deep tendon reflex (DTR) latency measurement in the diagnosis of SFN in patients with preserved DTR on clinical examination. We prospectively examined electromyographic reflexes from the biceps brachii [biceps brachii reflex (BR)], patellar [patellar reflex (PR)], and ankle [ankle reflex (AR)] using a manually operated electronic reflex hammer attached to electromyography machine and recorded by means of surface electrodes in 18 patients with SFN and 38 controls. Intra- and inter-evaluator reliability was good (intraclass correlation coefficient: 0.80-0.91, p < 0.01). In controls, the latencies at all sites were correlated to the height (R= 0.6, p < 0.01). Compared with controls, in patients with SFN, the mean latency in milliseconds was prolonged at all sites (BR: 12.8 +/- 1.6 vs. 8.9 +/- 1.9, p < 0.01; PR: 23.0 +/- 5.8 vs. 17.4 +/- 2.4, p < 0.01; and AR: 34.5 +/- 4.8 vs. 30.0 +/- 2.4, p < 0.01). The sensitivity [61.1% (95% CI: 51-94.9)] and specificity [92% (95% CI: 73-97.3)] of BR latency were roughly equal to those of PR and AR. We conclude that DTR latencies were significantly abnormal in the majority of the patients with SFN, suggestive of subclinical involvement of large myelinated fibers. DTR latency measurement is a reproducible, valuable, sensitive tool in the evaluation of mild subclinical involvement of large fibers. PMID- 17868251 TI - Multicentre study of peroneal mononeuropathy: multiperspective follow-up of nonsurgical cases. PMID- 17868252 TI - Abstracts of the XXVth Annual Scientific Meeting of the British Blood Transfusion Society, Glasgow, UK, 13-15 September 2007. PMID- 17868254 TI - Identification of a variant HLA-A*3401 allele, A*340102, in an educational DNA typing sample. AB - A*340102 was first identified in an ASEATTA Educational DNA typing sample, which typed as A*3401, 3401variant. The variant differs from A*3401 by a single silent substitution in exon 2 at nucleotide 309, codon 79 (GGG-->GGT). PMID- 17868255 TI - No association of KIR genes with Behcet's disease. AB - Behcet's disease (BD) is thought to be caused by multiple genetic, environmental and immunological factors, one of the most prominent being the strong association with human leucocyte antigen (HLA)-Bw51, an HLA-Bw4-associated allele. We examined the presence/absence of 14 killer cell immunoglobulin-like receptors (KIRs) and their ligands in 134 Turkish individuals with BD and compared the results with those of 154 ethnically matched controls. Although KIR3DL1 with its ligand (HLA-Bw4) was significantly increased in the patients with BD (P = 0.0003), this no longer applied when the patients and controls were categorised by HLA-Bw51 status. Thus, no association was identified between presence or absence of any of the 14 KIR genes studied and BD. In addition, we did not find any associations of KIR with various manifestations of the disease nor with gender or age of onset. PMID- 17868256 TI - PTPN22 gene polymorphism in Behcet's disease. AB - A functional single nucleotide polymorphism (SNP) of PTPN22 gene encoding the protein tyrosine phosphatase has been reported to be associated with autoimmune disorders such as rheumatoid arthritis, systemic lupus erythematosus and type I diabetes. PTPN22 R620W polymorphism has a wide variation of allelic frequencies among different populations. This polymorphism is investigated in Turkish patients with Behcet's disease (BD), a systemic vasculitis with immune activation. DNA samples from 134 patients with BD and 177 healthy controls are genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism method for the SNP (rs2476601, A/G) of PTPN22 gene. Polymorphic region was amplified by PCR and digested with XcmI enzyme. The frequency of heterozygous genotype (AG) was 5.1% (9/177) in control group, whereas polymorphic allele was not present in the whole BD group (P = 0.012, OR 0.65, 95% confidence interval 0.0-1.1). Both the lower prevalence in the general population and the absence in BD show the limited role of PTPN22 polymorphism in the pathogenesis of autoimmunity in Turkey. PMID- 17868257 TI - Identification of a novel allele HLA-DQB1*0622. AB - A novel human leukocyte antigen-DQ allele, DQB1*0622, was identified in a bone marrow transplantation candidate. DQB1*0622 differs from DQB1*0609 by two nucleotide differences in exon 2, position 122 (A-->T) and 177 (A-->G). The difference at position 122 resulted in an amino acid change (Tyrosine to Phenylalanine). However, the difference at position 177 did not cause any amino acid change. PMID- 17868258 TI - Reanalysis of sequence-based HLA-A, -B and -Cw typings: how ambiguous is today's SBT typing tomorrow. AB - The permanently increasing number of human leukocyte antigen (HLA)-alleles and the growing list of ambiguities require continuous updating of high-resolution HLA typing results. Two different kinds of ambiguities exist: the first, when two or more allele combinations have identical heterozygous sequences, and the second, when differences are located outside the analyzed region. The number of HLA-A, B and C alleles recognized in 1999 was almost tripled in 2006. Two hundred individuals, sequence-based typing (SBT) typed in the period from 1999 to 2002, were reanalyzed using the 2006 database. A final allele typing result of at least four digits was obtained for HLA-A, -B and -C by heterozygous sequencing of exons 2 and 3 and, if necessary, additional exons and/or allele-specific sequencing. Storage of the individual sequences in a specially developed database enabled reanalysis with all present and future HLA releases. In the 5-year period HLA-A, B and -C typing results became ambiguous in 37%, 46% and 41% of the cases. Most were because of differences outside the analyzed region; ambiguities because of different allele combinations with identical heterozygous sequences were present in 7%, 8% and 13% of the HLA-A, -B and -C typings. These results indicate that within 5 years, approximately half of the HLA SBT typings become ambiguous. PMID- 17868259 TI - Impaired maturation of monocyte-derived dendritic cells from birch allergic individuals in association with birch-specific immune responses. AB - Optimal activation of T lymphocytes requires a costimulatory signal provided by the interaction of molecules on the surface of T cells with their ligands expressed on dendritic cells (DC). We investigated whether DC differentiated from monocytes from healthy and birch allergic asthmatic individuals and further maturated by stimulation with cat and birch allergens and LPS differ in their phenotypic receptor expression. Similar expression of DC surface markers, including HLA-DR, CD80, CD86, CD83, CD1a and CD11c, was detected in monocyte derived DC from allergic and healthy individuals. Cells from healthy donors stimulated either antigen showed a similar activation of the CD80 and double CD80/CD86 costimulatory molecules when compared with non-stimulated cells. In the case of cells from allergic individuals, birch allergen was unable to produce the same increased expression of CD80 alone or in combination with CD80/CD86, in comparison with cells stimulated with cat and LPS. Levels of IL-6, IL-8, IL-10, MCP-1/MCAF and MIP-1beta were similar in the supernatant of non-stimulated DC from both groups of subjects. By contrast, the spontaneous secretion of IL-12p70 and TNF-alpha was higher in the supernatant of DC from healthy subjects when compared with that from allergic individuals. Stimulation with birch and LPS resulted in an increased secretion of IL-12p70 in samples from healthy when compared with that in allergic individuals. The results suggest an impaired specific maturation of DC from birch allergic individuals in association with birch-specific immune responses. Lower secretion of IL-12p70 from birch stimulated DC from allergic individuals suggests that not only maturation, but also the specific Th1 function of these cells seems to be affected in those individuals. PMID- 17868260 TI - Peripheral circulating activated b-cell populations are associated with nephritis and disease activity in patients with systemic lupus erythematosus. AB - B-cell-dependent autoantibody production is a hallmark of systemic lupus erythematosus (SLE) which requires costimulatory molecules. The aim of the study was to analyse the expression of costimulatory molecules on B cells in patients with SLE. Twenty-six patients with SLE (four male, 22 female, mean age 46 +/- 15 years) as defined by the American College of Rheumatology criteria and 13 healthy controls (three male, 10 female, mean age 43 +/- 15 years) were included in the study. In a subgroup analysis, SLE patients were divided according to renal involvement due to SLE (10 with and 16 patients without renal involvement). Clinical disease activity was assessed according to the systemic lupus erythematosus disease activity index (SLEDAI). Blood B-cell populations were analysed by FACS for the cell surface marker expression of CD27, CD38, CD71, CD80, CD86 and CD137 ligand. The expression levels of CD71, CD80 and CD86 on B cells were significantly enhanced in SLE patients when compared with healthy controls (27 +/- 3% versus 11 +/- 2%, P = 0.0003, 55 +/- 2% versus 28 +/- 4%, P < 0.0001, 34 +/- 3% versus 12 +/- 2%, P < 0.0001). CD86 expression was significantly elevated in patients with renal involvement when compared with patients without renal disease (43 +/- 6% versus 28 +/- 3%, P < 0.05). There was a significant correlation between the expression levels of CD80 and CD86 on CD19(+) B cells and disease activity. Moreover, prednisone dose significantly correlated with SLEDAI (r = 0.5, P = 0.02) and with the expression levels of CD86 (r = 0.47, P = 0.02). A pathological B-cell population is associated with disease activity and renal involvement in SLE which are obviously resistant to therapy with medium doses of prednisone. PMID- 17868262 TI - MMN or no MMN: no magnitude of deviance effect on the MMN amplitude. AB - Based on results showing that the "deviant-minus-standard" estimate of the mismatch negativity (MMN) amplitude increases with increasing amounts of deviance, it has been suggested that the MMN amplitude reflects the amount of difference between the neural representations of the standard and the deviant sound. However, the deviant-minus-standard waveform also includes an N1 difference. We tested the effects of the magnitude of deviance on MMN while minimizing this N1 confound. We found no significant magnitude of deviance effect on the genuine MMN amplitude. Thus we suggest that the average MMN amplitude does not reflect the difference between neural stimulus representations; rather it may index the percentage of detected deviants, each of which elicits an MMN response of uniform amplitude. These results are compatible with an explanation suggesting that MMN is involved in maintaining a neural representation of the auditory environment. PMID- 17868263 TI - Association and not semantic relationships elicit the N400 effect: electrophysiological evidence from an explicit language comprehension task. AB - Language comprehension studies have identified the N400, an event-related potential (ERP) correlate of the processing of meaning, modulation of which is typically assumed to reflect the activation of semantic information. However, N400 studies of conscious language processing have not clearly distinguished between meaning derived from a semantic relationship and meaning extracted through association. We independently manipulated the presence of associative and semantic relationships while examining the N400 effect. Participants were asked to read and remember visually presented word pairs that shared an association (traffic-jam), an association+semantic relationship (lemon-orange), a semantic relationship alone (cereal-bread), or were unrelated (beard-tower). Modulation of the N400 (relative to unrelated word pairs) was observed for association and association+semantic word pairs but not for those that only shared a semantic relationship. PMID- 17868261 TI - Dissociation of sad facial expressions and autonomic nervous system responding in boys with disruptive behavior disorders. AB - Although deficiencies in emotional responding have been linked to externalizing behaviors in children, little is known about how discrete response systems (e.g., expressive, physiological) are coordinated during emotional challenge among these youth. We examined time-linked correspondence of sad facial expressions and autonomic reactivity during an empathy-eliciting task among boys with disruptive behavior disorders (n=31) and controls (n=23). For controls, sad facial expressions were associated with reduced sympathetic (lower skin conductance level, lengthened cardiac preejection period [PEP]) and increased parasympathetic (higher respiratory sinus arrhythmia [RSA]) activity. In contrast, no correspondence between facial expressions and autonomic reactivity was observed among boys with conduct problems. Furthermore, low correspondence between facial expressions and PEP predicted externalizing symptom severity, whereas low correspondence between facial expressions and RSA predicted internalizing symptom severity. PMID- 17868264 TI - The relationship of methanol and formate concentrations in fatalities where methanol is detected. AB - An automated headspace gas chromatography method was developed for the determination of formate (formic acid) in postmortem specimens, based on the in situ sulfuric acid-methanol methylation of formic acid to methyl formate. Diisopropyl ether was used as an internal standard. The method was applied to over 150 postmortem cases where methanol was detected. Of the 153 cases presented, 107 deaths were attributed to acute methanol toxicity. In the vast majority of the remaining 46 deaths, the methanol was determined to be present as a postmortem or perimortem artifact, or was otherwise incidental to the cause of death. Of the 76 victims who were found dead and blood was collected by the medical examiner, all but one had a postmortem blood formate concentration greater than 0.50 g/L (mean 0.85 g/L; n = 74). The sole exception involved suicidal ingestion of methanol where the blood methanol concentration was 7.9 g/L (790 mg/100 mL) and blood formate 0.12 g/L. In 97% (72/74) of the cases where blood was available, the blood formate was between 0.60 and 1.40 g/L. In 31 of the 153 cases, the victim was hospitalized and blood obtained on admission or soon after was analyzed for methanol and formate during the subsequent death investigation; the vast majority (27/30) had antemortem blood formate concentrations greater than 0.50 g/L. Cases with samples taken prior to death with blood formate concentrations less than 0.5 g/L can readily be explained by active treatment such as dialysis. The blood formate method has also been useful in confirming probable perimortem or postmortem contamination of one of more fluids or tissues with methanol (e.g., windshield washer fluid or embalming fluid), where methanol ingestion was unlikely. PMID- 17868265 TI - Routine forensic use of the mitochondrial 12S ribosomal RNA gene for species identification. AB - Since July 2004, Mitotyping Technologies has been amplifying and sequencing a approximately 150 base pair fragment of mitochondrial DNA (mtDNA) that codes for 12S ribosomal RNA, to identify the species origin of nonhuman casework samples. The approximately 100 base pair sequence product is searched at http://www.ncbi.nlm.nih.gov/BLAST and the species match is reported. The use of this assay has halved the number of samples for which no mtDNA results are obtained and is especially useful on hairs and degraded samples. The availability of species determination may aid forensic investigators in opening or closing off lines of inquiry where a highly probative but challenging sample has been collected. PMID- 17868266 TI - Macroscopic characteristics of screwdriver trauma. AB - The main objective of the study was to determine the type of macroscopic trauma created by a flat-tipped and a cross-tipped screwdriver. The second objective was to determine if the trauma inflicted by the two screwdrivers could be macroscopically differentiated. Three tests were conducted, each by a male volunteer. Each test consisted of 12 samples of fleshed pig ribs; six were stabbed with a flat-tipped screwdriver and the remaining six with a cross-tipped screwdriver (Phillips). Each sample received 15 stab wounds during the process. The stabbings were conducted at perpendicular and oblique angles, with fabric variables being utilized. Results illustrate two main categories of macroscopic skeletal trauma, fractures, and puncture wounds. By studying the macroscopic appearance in tandem with differing trauma frequencies, these two screwdriver types can be differentiated. PMID- 17868267 TI - Recovery and detection of urea nitrate in traces. AB - Urea nitrate (uronium nitrate, UN) is a powerful improvised explosive, frequently used by terrorists in the Israeli arena. It was also used in the first World Trade Center bombing in New York in February 1993. It is difficult to identify UN in postexplosion debris, because in the presence of water it readily decomposes to its original components, urea and nitric acid. A method for the recovery and detection of urea nitrate in traces is described. The residues are extracted with hot acetone, and the extract chromatographed on chromosorb G-HP. The eluent is analyzed by liquid chromatography mass spectrometry using atmospheric pressure chemical ionization (APCI). By applying this technique, we were able to identify urea nitrate in actual exhibits. It was found that UN can be also formed during the analytical procedure, by certain combinations of urea, nitrate ions, and a source of protons and, hence, the presence of the characteristic adduct ion does not necessarily indicate an "authentic" urea nitrate. Several solutions are suggested to overcome this ambiguity. PMID- 17868268 TI - mRNA profiling for body fluid identification by multiplex quantitative RT-PCR. AB - An alternative approach to conventional protein-based body fluid identification is gene expression profiling analysis. In the present work, we report the development of sensitive and robust multiplex quantitative reverse transcriptase PCR assays for the identification of blood, saliva, semen, and menstrual blood. Each body fluid assay comprises a triplex system that detects transcripts from two body fluid-specific genes and a housekeeping gene GAPDH. The body fluid specific genes include erythroid delta-aminolevulinate synthase (ALAS2) and beta spectrin (SPTB) for blood, statherin (STATH) and histatin 3 (HTN3) for saliva, protamine 1 (PRM1) and protamine 2 (PRM2) for semen, and matrix metalloproteinase 7 (MMP7) and matrix metalloproteinase 10 (MMP10) for menstrual blood. Normalization of both body fluid-specific genes to the housekeeping gene by means of appropriate cycle threshold metrics ensures the high specificity of each assay for its cognate body fluid. PMID- 17868269 TI - The role of center of mass kinematics in predicting peak utilized coefficient of friction during walking. AB - Slips frequently occur when the friction required between the foot and floor exceeds available surface slip resistance. To date, the ability to identify variables that predict an individual's friction needs during walking, or utilized coefficient of friction (COFU), remains limited. Understanding COFU in the context of pedestrian/walkway accidents is important as individuals who demonstrate higher COFU are at a greater risk of slipping. This study determined if whole body center of mass (CM) kinematics were predictive of peak COFU during walking. Ground reaction forces and kinematic data were recorded simultaneously as subjects walked. Stepwise regression analysis determined that the combination of the subject's CM-to-center-of-pressure angle and CM anterior (i.e., forward) velocity predicted 62% of the variance in peak COFU during weight acceptance (p < 0.001). The identified relationships between CM kinematics and peak COFU provide insight into how gait and individual anthropometric characteristics may increase risk for slip initiation. PMID- 17868270 TI - The role of mobile computed tomography in mass fatality incidents. AB - Mobile multi-detector computed tomography (MDCT) scanners are potentially available to temporary mortuaries and can be operational within 20 min of arrival. We describe, to our knowledge, the first use of mobile MDCT for a mass fatality incident. A mobile MDCT scanner attended the disaster mortuary after a five vehicle road traffic incident. Five out of six bodies were successfully imaged by MDCT in c. 15 min per body. Subsequent full radiological analysis took c. 1 h per case. The results were compared to the autopsy examinations. We discuss the advantages and disadvantages of imaging with mobile MDCT in relation to mass fatality work, illustrating the body pathway process, and its role in the identification of the pathology, personal effects, and health and safety hazards. We propose that the adoption of a single modality of mobile MDCT could replace the current use of multiple radiological sources within a mass fatality mortuary. PMID- 17868271 TI - The role of environmental factors in the causation of sudden death in infants: two cases of sudden unexpected death in two unrelated infants who were cared for by the same babysitter. AB - We report two cases of sudden unexpected death in two unrelated African American female infants, 2 months and 4 months old. Both infants were attended to by the same babysitter in the same apartment and died 39 days apart in the same bed and in the same bedroom. The autopsy of the first infant revealed sudden unexplained death in an infant. Toxicologic analysis for carbon monoxide (CO) was not performed because it was not suspected. When the second infant died, investigation into the ambient air quality within the apartment revealed high levels of CO emanating from a poorly ventilated and defective hot water heater, which was located across a hallway from the bedroom where the two babies died. CO saturation levels in the postmortem blood samples of the two babies were elevated and were similar (13% and 14%). Nicotine and cotinine were not detected in the blood sample of the two infants. Cherry-red livor mortis was absent. Acute CO intoxication was determined to be the underlying cause of these two unexpected deaths. These two cases underscore the need to integrate ambient air analysis and postmortem CO analysis as routine components of the comprehensive death investigation of infants who die suddenly and unexpectedly. PMID- 17868272 TI - Determination of season at death using dental cementum increment analysis. AB - Dental cementum anchors teeth into their sockets via the periodontal ligament. In mammals, dental cementum is laid down in alternating opaque and translucent bands representing winter (dormant) and summer (growth) seasons. Each pair of bands represents 1 year of life. Estimates of age at death based on counting pairs of bands are highly accurate. If the timing of the transition between winter and summer bands could be identified in humans, dental cementum increment analysis could be used to specify the season at death. This pilot project attempts to determine when these transitions occur and thus provide forensic anthropologists with a technique that would refine our estimates of postmortem interval. Extracted teeth were obtained from a local oral surgeon, embedded, sectioned, ground, polished, and examined under transmitted polarized light. The outermost increment was identified and measured along with other randomly chosen like bands. A transition from translucent to opaque bands was observed in teeth extracted in early October, while teeth extracted in early April exhibited nascent translucent bands. Further, significant correlations were observed between band thickness and number of days into either season, suggesting that band width increases as either season progresses. In this blind study, extracted teeth were effectively sorted into the spring/summer or fall/winter season 99% of the time. PMID- 17868273 TI - Vascular events after liver transplantation: a long-term follow-up study. AB - Long-term follow-up studies on the impact of vascular events (VE) and risk factors of liver transplant recipients are scarce. In this study, 311 recipients of a first isolated liver transplant who survived at least 1 year were followed up from 1979 to 2002. The median follow-up duration was 6.2 (range1-22.7) years. Overall median survival was 18.7 [95% confidence interval (CI): 15.5-20.1] years and this was significantly lower compared with age- and sex-matched controls. Eleven (21%) of the patients had a vascular cause of death and VE were the third cause of death. VE occurred later compared with other causes of death (mean 10.3 years vs. 4.5 years, P < 0.0001, 95% CI: 2.7-8.9). Systolic hypertension, systolic blood pressure, smoking, renal failure, age, hypertriglyceridemia, serum total cholesterol levels and hypercholesterolemia at the 1-year follow-up visit were associated with the occurrence of VE, but renal failure and age at 1 year after transplantation were the only independent risk factors for vascular death (hazard ratio 0.06, 95% CI: 0.01-0.41 and hazard ratio 1.17, 95% CI: 1.02-1.34, respectively). Finally, it was shown that the adequate treatment of hypertension was associated with a significant reduced risk of vascular death. Therefore, vascular risk factors should be treated aggressively to prevent VE in the long term. PMID- 17868274 TI - Orthotopic liver transplantation for subacute hepatic failure following partial treatment of isoniazid-resistant tuberculosis. AB - The management of patients with pre-existing tuberculosis (TB) undergoing liver transplantation is challenging. Cautious immunosuppression is required to prevent reactivation of disease, and second-line anti-tuberculous treatment may be necessary to prevent graft hepatotoxicity. Furthermore, liver transplantation in the context of isoniazid-resistant TB has seldom been reported. We report on a 44 year-old man with recent isoniazid-resistant extra-pulmonary TB who developed subacute hepatic failure requiring emergency liver transplantation and treatment with second-line anti-tuberculous therapy. We demonstrate that patients who have pre-existing TB can be successfully treated with alternative anti-tuberculous medication while under immunosuppression post transplantation. Pre-existing TB, including resistant strains, should not be an absolute contraindication to liver transplantation. PMID- 17868275 TI - Laparoscopic para-aortic lymphadenectomy and positron emission tomography scan as staging procedures in patients with cervical carcinoma stage IB2-IIIB. AB - The objective of this study was to determine the role of laparoscopic lower para aortic lymphadenectomy and positron emission tomography (PET) scan in the staging of cervical carcinoma. Ninety consecutive patients with FIGO stage IB2-IIIB were scheduled for laparoscopic para-aortic lymphadenectomy. EXCLUSION CRITERIA: obvious metastatic para-aortic nodes on computed tomography (CT)/PET or PET-CT. The procedure was stopped when a node was positive on frozen section. In ten patients, no para-aortic lymphadenectomy was performed as scheduled. Forty-seven patients were operated retroperitoneally, 22 transperitoneally, and 21 cases were converted from retroperitoneally to transperitoneally. Median number of removed nodes was 6 (1-24). In 10 of 80 patients, para-aortic metastases were diagnosed. Despite a nonsuspect PET result, 5 of 44 patients had positive para-aortic nodes. Two-year survival was 76% and 16% without and with para-aortic metastases, respectively (P = 0.0001). Laparoscopic para-aortic lymphadenectomy showed metastases in 13% of the patients. In the subgroup with negative PET scan, 11% had metastases. The procedure had a low morbidity and identified a group with an extremely poor prognosis. PMID- 17868276 TI - A novel compound heterozygous dysferlin mutation in Miyoshi myopathy siblings responding to dantrolene. AB - Miyoshi myopathy (MM) is an autosomal recessive distal muscular dystrophy characterized by mutations of the dysferlin gene. Although several pairs of homozygous/heterozygous mutations have been reported, few effective treatments of MM are available. We had observed the decreased serum creatine kinase (CK) before and after administration of dantrolene in the elder brother and the increased serum CK before and after discontinuance of the drug on suspicion of drug-induced hepatopathy in the younger sister. We report a novel pair of heterozygous mutations in the 3'-splicing site of exon 26 and the translation site of exon 28 of the dysferlin gene in two siblings, and effective treatment of their MM with dantrolene. PMID- 17868277 TI - Intercellular adhesion molecule-1 gene polymorphism in Iranian patients with multiple sclerosis. AB - Intercellular adhesion molecule-1 (ICAM-1), an important molecule in leucocyte activation and migration, is expressed on the CNS endothelial cells of patients with multiple sclerosis. This study was conducted to determine whether ICAM-1 gene polymorphism influences the risk of developing multiple sclerosis in an Iranian population. We studied 157 patients with definite multiple sclerosis and 156 ethnically matched controls. The patients and the controls were genotyped for ICAM-1 gene polymorphism at codons 241 (exon 4) and 469 (exon 6). G/R241 and K/E 469 allele and genotype distribution did not show any significant difference between patient and control groups. We concluded that role of the ICAM-1 gene polymorphisms in the pathogenesis of multiple sclerosis is still controversial and should be studied further. PMID- 17868278 TI - Cerebral venous thrombosis caused by spontaneous intracranial hypotension: two cases. AB - The association of spontaneous intracranial hypotension (SIH) with cerebral venous thrombosis (CVT) is rare. We are reporting two new cases. In one case, CVT is extensive concerning three sinuses and bilateral parietal cortical veins and, in the other case, only a cortical vein is involved. Both the patients presented had no thrombosis risk factors. There is certainly a link between these two pathologies. SIH should be considered as a risk factor of CVT. Modification of symptoms of SIH leading to CVT must be known to start early treatment. PMID- 17868279 TI - Subcortical ischaemic changes in young hypertensive patients: frequency, effect on cognitive performance and relationship with markers of endothelial and haemostatic activation. AB - Information on subcortical ischaemic changes (SIC) in young hypertensive patients is scarce. We evaluated the frequency of SIC at magnetic resonance imaging (MRI), the possible effect on cognition of these patients, and the role of plasma markers known as indicators of endothelial and haemostatic activation. Inclusion criteria were age 10-fold) induced in differentiated RN46A cells, but not in GH4C1 cells. This effect was blocked by actinomycin D, implicating transcriptional activation. Similarly, calcium ionophore ionomycin induced TPH2 RNA by threefold in RN46A cells. To address the promoter sites involved, the transcription start site was identified and a series of TATA-containing TPH2 promoter-luciferase constructs were analyzed. In differentiated RN46A cells, the TPH2 promoter was induced 2.5-fold by ionomycin, similar to its action on TPH2 RNA. By contrast, ionomycin had no effect on TPH2 promoter activity in GH4C1 cells or TPH2-negative L6 myoblasts. Ionomycin sensitivity was localized to within 88 bp of the start site, containing putative CCATT-enhancer binding protein element, activator protein-1 and -2 (AP 1, AP-2) elements. These results are the first to identify calcium-mediated regulation of the proximal TPH2 promoter as critical for cell-specific TPH2 expression. PMID- 17868302 TI - Brain-to-blood elimination of 24S-hydroxycholesterol from rat brain is mediated by organic anion transporting polypeptide 2 (oatp2) at the blood-brain barrier. AB - 24S-Hydroxycholesterol (24S-OH-chol), a major cerebral cholesterol metabolite, is an endogenous ligand for the liver X receptor and is a potential stimulant of cholesterol release from glial cells. The elimination mechanism of 24S-OH-chol from the brain is one of the key issues for understanding cerebral cholesterol homeostasis. The purpose of the present study was to clarify the molecular mechanism of the elimination process of 24S-OH-chol across the blood-brain barrier (BBB). After an intracerebral injection in rats, [(3)H]24S-OH-chol was eliminated from the brain and the radioactivity derived from [(3)H]24S-OH-chol was detected in the plasma, while [(3)H]cholesterol was not significantly eliminated from the brain. Co-administration of unlabeled 24S-OH-chol significantly inhibited the [(3)H]24S-OH-chol elimination, while no inhibitory effect was seen at the same concentration of cholesterol. The [(3)H]24S-OH-chol elimination was inhibited by co-administration of probenecid, but not by benzylpenicillin. Pre-administration of digoxin completely inhibited the elimination. Xenopus laevis oocytes expressing rat oatp2 exhibited significant transport of [(3)H]24S-OH-chol, and this was inhibited by unlabeled 24S-OH-chol and digoxin, indicating that rat oatp2 transports 24S-OH-chol. These results are the first direct demonstration that 24S-OH-chol undergoes elimination from the brain to blood across the BBB via a carrier-mediated process, which involves oatp2 expressed at the BBB in rats. PMID- 17868303 TI - Intracellular signaling mechanisms mediating catecholamine release upon activation of NPY Y1 receptors in mouse chromaffin cells. AB - The adrenal chromaffin cells synthesize and release catecholamine (mostly epinephrine and norepinephrine) and different peptides, such as the neuropeptide Y (NPY). NPY stimulates catecholamine release through NPY Y1 receptor in mouse chromaffin cells. The aim of our study was to determine the intracellular signaling events coupled to NPY Y1 receptor activation that lead to stimulation of catecholamine release from mouse chromaffin cells. The stimulatory effect of NPY mediated by NPY Y1 receptor activation was lost in the absence of extracellular Ca2+. On the other hand, inhibition of nitric oxide synthase and guanylyl cyclase also decreased the stimulatory effect of NPY. Moreover, catecholamine release stimulated by NPY or by the nitric oxide donor (NOC-18) was inhibited by mitogen-activated protein kinase (MAPK) and protein kinase C inhibitors. In summary, in mouse chromaffin cells, NPY evokes catecholamine release by the activation the NPY Y1 receptor, in a Ca2+-dependent manner, by activating mitogen-activated protein kinase and promoting nitric oxide production, which in turn regulates protein kinase C and guanylyl cyclase activation. PMID- 17868304 TI - G protein-coupled receptor oligomerization provides the framework for signal discrimination. AB - The idea that G protein-coupled receptors (GPCRs) may undergo homo- or hetero oligomerization, although highly controversial up to a few years ago, has recently gained wide acceptance. The recognition that GPCRs may exhibit either dimeric or oligomeric structures is based upon a large body of biochemical and biophysical evidence. While much effort has been spent to demonstrate the mechanism(s) by which GPCRs interact with each other, the physiological relevance of this phenomenon remains rather elusive. GPCR oligomerization has been proposed to play a role in receptor ontogeny by either chaperoning protein folding or controlling trafficking to the cell surface. However, the acquisition of these roles does not rule out the possibility that oligomeric receptors may have additional functions, once they are brought to the cell surface. Herein, we propose that protein-protein as well as protein-lipid interactions may provide the structural basis for organizing distinct cell compartments along the plasma membrane where different extracellular signals may be perceived and discriminated. PMID- 17868305 TI - Pituitary adenylate cyclase-activating polypeptide is up-regulated in cortical pyramidal cells after focal ischemia and protects neurons from mild hypoxic/ischemic damage. AB - The protective effect of pituitary adenylate cyclase-activating polypeptide (PACAP) in stroke models is poorly understood. We studied patterns of PACAP, vasoactive intestinal peptide, and the PACAP-selective receptor PAC1 after middle cerebral artery occlusion and neuroprotection by PACAP in cortical cultures exposed to oxygen/glucose deprivation (OGD). Within hours, focal ischemia caused a massive, NMDA receptor (NMDAR)-dependent up-regulation of PACAP in cortical pyramidal cells. PACAP expression dropped below the control level after 2 days and was normalized after 4 days. Vasoactive intestinal peptide expression was regulated oppositely to that of PACAP. PAC1 mRNA showed ubiquitous expression in neurons and astrocytes with minor changes after ischemia. In cultured cortical neurons PACAP27 strongly activated Erk1/2 at low and p38 MAP kinase at higher nanomolar concentrations via PAC1. In astrocyte cultures, effects of PACAP27 on Erk1/2 and p38 were weak. During OGD, neurons showed severely reduced Erk1/2 activity and dephosphorylation of Erk1/2-regulated Ser112 of pro-apoptotic Bad. PACAP27 stimulation counteracted Erk1/2 inactivation and Bad dephosphorylation during short-term OGD but was ineffective after expanded OGD. Consistently, PACAP27 caused MEK-dependent neuroprotection during mild but not severe hypoxic/ischemic stress. While PACAP27 protected neurons at 1-5 nmol/L, full PAC1 activation by 100 nmol/L PACAP exaggerated hypoxic/ischemic damage. PACAP27 stimulation of astrocytes increased the production of Akt-activating factors and conferred ischemic tolerance to neurons. Thus, ischemia-induced PACAP may act via neuronal and astroglial PAC1. PACAP confers protection to ischemic neurons by maintaining Erk1/2 signaling via neuronal PAC1 and by increasing neuroprotective factor production via astroglial PAC1. PMID- 17868306 TI - Changes in brain levels of N-acylethanolamines and 2-arachidonoylglycerol in focal cerebral ischemia in mice. AB - The N-acylethanolamines (NAEs) and 2-arachidonoylglycerol (2-AG) are bioactive lipids that can modulate inflammatory responses and protect neurons against glutamatergic excitotoxicity. We have used a model of focal cerebral ischemia in young adult mice to investigate the relationship between focal cerebral ischemia and endogenous NAEs. Over the first 24 h after induction of permanent middle cerebral artery occlusion, we observed a time-dependent increase in all the investigated NAEs, except for anandamide. Moreover, we found an accumulation of 2 AG at 4 h that returned to basal level 12 h after induction of ischemia. Accumulation of NAEs did not depend on regulation of N acylphosphatidylethanolamine-hydrolyzing phospholipase D or fatty acid amide hydrolase. Treatment with the fatty acid amide hydrolase inhibitor URB597 (cyclohexyl carbamic acid 3'-carbamoyl-biphenyl-3-yl ester; 1 mg/kg; i.p.) 1.5 h before arterial occlusion decreased the infarct volume in our model system. Our results suggest that NAEs and 2-AG may be involved in regulation of neuroprotection during focal cerebral ischemia in mice. PMID- 17868307 TI - Constitutive endocytosis and recycling of the neuronal glutamate transporter, excitatory amino acid carrier 1. AB - The neuronal glutamate transporter, excitatory amino acid carrier 1 (EAAC1), has a diverse array of physiologic and metabolic functions. There is evidence that there is a relatively large intracellular pool of EAAC1 both in vivo and in vitro, that EAAC1 cycles on and off the plasma membrane, and that EAAC1 cell surface expression can be rapidly regulated by intracellular signals. Despite the possible relevance of EAAC1 trafficking to both physiologic and pathologic processes, the cellular machinery involved has not been defined. In the present study, we found that agents that disrupt clathrin-dependent endocytosis or plasma membrane cholesterol increased steady-state levels of biotinylated EAAC1 in C6 glioma cells and primary neuronal cultures. Acute depletion of cholesterol increased the V(max) for EAAC1-mediated activity and had no effect on Na(+) dependent glycine transport in the same system. These agents also impaired endocytosis as measured using a reversible biotinylating reagent. Co-expression with dominant-negative variants of dynamin or the clathrin adaptor, epidermal growth factor receptor pathway substrate clone 15, increased the steady-state levels of biotinylated myc-EAAC1. EAAC1 immunoreactivity was found in a subcellular fraction enriched in early endosome antigen 1 (EEA1) isolated by differential centrifugation and partially co-localized with EEA1. Co-expression of a dominant-negative variant of Rab11 (Rab11 S25N) reduced steady-state levels of biotinylated myc-EAAC1 and slowed constitutive delivery of myc-EAAC1 to the plasma membrane. Together, these observations suggest that EAAC1 is constitutively internalized via a clathrin- and dynamin-dependent pathway into early endosomes and that EAAC1 is trafficked back to the cell surface via the endocytic recycling compartment in a Rab11-dependent mechanism. As one defines the machinery required for constitutive trafficking of EAAC1, it may be possible to determine how intracellular signals regulate EAAC1 cell surface expression. PMID- 17868308 TI - P2Y2 nucleotide receptors inhibit trauma-induced death of astrocytic cells. AB - Nucleotides as well as other neurotransmitters are known to be released to the extracellular space upon injury. To determine whether nucleotides acting on P2Y(2) nucleotide receptors promote protective or degenerative events after trauma in astrocytic cells, a well-established model of in vitro brain trauma was applied to 1321N1 cells expressing recombinant P2Y(2) nucleotide receptors (P2Y(2)R-1321N1). Cellular death was examined by measuring DNA fragmentation and caspase activation. Fragmented DNA was observed 48 h post-injury in 1321N1 cells, while P2Y(2) nucleotide receptor expressing cells did not show DNA fragmentation. A laddering pattern of fragmented DNA following injury was observed upon inhibition of P2Y(2) nucleotide receptors with suramin. Time-dependent increases of cleaved caspase-9, a mitochondrial-associated caspase, correlated with injury induced cellular death. A decreased bax/bcl-2 gene expression ratio was observed in P2Y(2)R-1321N1 cells after traumatic injury, while untransfected 1321N1 cells showed a significant time-dependent increase of the bax/bcl-2 gene expression ratio. Activation of protein kinases was assessed to determine the signaling pathways involved in cell death and survival responses following traumatic injury. In P2Y(2)R-1321N1 and 1321N1 cells p38 phosphorylation was stimulated in a time-dependent manner but the phosphatidylinositol 3-kinase-dependent activation of extracellular signal-regulated kinase 1/2 and protein kinase B (PKB)/Akt was only observed in P2Y(2)R-1321N1 cells after injury. The stress activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) signaling pathway was not activated by traumatic injury in either astrocytic cell line. Inhibition of p38 kinase signaling pathway by treatment with PD1693, a MKK3/6 inhibitor, abolished the expression of cleaved caspase-9, the increase in the bax/bcl-2 gene expression ratio, as well as the fragmentation of DNA that followed injury of 1321N1 cells. Taken together, our results demonstrate a novel role for P2Y(2) nucleotide receptors and extracellular nucleotides in mediating survival responses to glial cells undergoing cellular death induced by trauma. PMID- 17868309 TI - Plant reproductive systems and evolution during biological invasion. AB - Recent biological invasions provide opportunities to investigate microevolution during contemporary timescales. The tempo and scope of local adaptation will be determined by the intensity of natural selection and the amounts and kinds of genetic variation within populations. In flowering plants, genetic diversity is strongly affected by interactions between reproductive systems and stochastic forces associated with immigration history and range expansion. Here, we explore the significance of reproductive system diversity for contemporary evolution during plant invasion. We focus in particular on how reproductive modes influence the genetic consequences of long-distance colonization and determine the likelihood of adaptive responses during invasion. In many clonal invaders, strong founder effects and restrictions on sexual reproduction limit opportunities for local adaptation. In contrast, adaptive changes to life-history traits should be a general expectation in both outbreeding and inbreeding species. We provide evidence that evolutionary modifications to reproductive systems promote the colonizing ability of invading populations and that reproductive timing is an important target of selection during range expansion. Knowledge of the likelihood and speed at which local adaptation evolves in invasive plants will be particularly important for management practices when evolutionary changes enhance ecological opportunities and invasive spread. PMID- 17868310 TI - The effects of cyclic dynamics and mating system on the effective size of an island mouflon population. AB - The Haute Island mouflon (Ovis aries) population is isolated on one small (6.5 km2) island of the remote Kerguelen archipelago. Given a promiscuous mating system, a cyclic demography and a strong female-biased sex ratio after population crashes, we expected a low effective population size (Ne). We estimated Ne using demographic and temporal genetic approaches based on genetic information at 25 microsatellite loci from 62 and 58 mouflons sampled in 1988 and 2003, respectively. Genetic Ne estimates were higher than expected, varying between 104 and 250 depending on the methods used. Both demographic and genetic approaches show the Haute Island Ne is buffered against population crashes. The unexpectedly high Ne likely results from the cyclic winter crashes that allow young males to reproduce, limiting the variance of male reproductive success. Based on individual-based simulations, we suggest that despite a strongly female-biased sex ratio, the effects of the mating system on the effective population size more closely resemble random mating or weak polygyny. PMID- 17868311 TI - Multi-locus DNA sequence data reveal a history of deep cryptic vicariance and habitat-driven convergence in the desert night lizard Xantusia vigilis species complex (Squamata: Xantusiidae). AB - The lizard genus Xantusia of southwestern North America has received recent attention in relation to delimiting species. Using more than 500 lizards from 156 localities, we further test hypothesized species boundaries and clarify phylogeographical patterns, particularly in regions of potential secondary contact. We sequenced the entire mitochondrial cytochrome b gene for every lizard in the study, plus a second mitochondrial DNA (mtDNA) region and two nuclear introns for subsets of the total sample. Phylogenetic analyses of the mtDNA recover a well-resolved, novel hypothesis for species in the Xantusia vigilis complex. The nuclear DNA (nDNA) data provide independent support for the recognition of X. arizonae, X. bezyi and X. wigginsi. Differences between the respective mtDNA and nDNA topologies result from either the effects of lineage sorting or ancient introgression. Nuclear data confirm the inference that some populations of X. vigilis in northwestern Arizona converged on rock-crevice dwelling morphology and are not X. arizonae with an introgressed X. vigilis mtDNA genome. The historical independence of ancient cryptic lineages of Xantusia in southern California is also corroborated, though limited introgression is detected. Our proposed biogeographical scenario indicates that diversification of this group was driven by vicariance beginning in the late Miocene. Additionally, Pleistocene climatical changes influenced Xantusia distribution, and the now inhospitable Colorado Desert previously supported night lizard presence. The current taxonomy of the group likely underestimates species diversity within the group, and our results collectively show that while convergence on the rock crevice-dwelling morphology is one hallmark of Xantusia evolution, morphological stasis is paradoxically another. PMID- 17868312 TI - Reduction of ferric green rust by Shewanella putrefaciens. AB - AIMS: To reduce carbonated ferric green rust (GR*) using an iron respiring bacterium and obtain its reduced homologue, the mixed Fe(II)-Fe(III) carbonated green rust (GR). METHODS AND RESULTS: The GR* was chemically synthesized by oxidation of the GR and was incubated with Shewanella putrefaciens cells at a defined [Fe(III)]/[cell] ratio. Sodium methanoate served as the sole electron donor. The GR* was quickly transformed in GR (iron reducing rate = 8.7 mmol l(-1) h(-1)). CONCLUSIONS: Ferric green rust is available for S. putrefaciens respiration as an electron acceptor. The reversibility of the GR redox state can be driven by bacterial activity. SIGNIFICANCE AND IMPACT OF THE STUDY: This work suggests that GRs would act as an electronic balance in presence of bacteria. It provides also new perspectives for using iron reducing bacterial activity to regenerate the reactive form of GR during soil or water decontamination processes. PMID- 17868313 TI - Detection of Staphylococcus aureus and enterotoxin genotype diversity in Monte Veronese, a Protected Designation of Origin Italian cheese. AB - AIMS: To evaluate the risk associated with the load and enterotoxigenicity of Staphylococcus aureus in Monte Veronese, a PDO (Protected Designation of Origin) cheese of the Lessinia area (Verona, Italy). METHODS AND RESULTS: Staphylococcus aureus was quantified by a conventional culture method and by a nucA targeted real-time PCR assay developed in this study. Staphylococcus aureus numbers in cheese were higher than the limit tolerated by the Italian food legislation in 78% instances, according to both detection methods. Multiplex PCR tests for 17 Staph. aureus enterotoxin (SE) genes were applied to nucleic acids extracted from curds, cheeses and Staph. aureus isolates. The SE gene diversity appeared reduced after ripening. The gene encoding SED was found most frequently in dairy samples and the enterotoxin genes ser, sed, seg and sem predominated in the isolates. CONCLUSIONS: The occurrence of enterotoxigenic Staph. aureus strains with complex SE genotypes in this PDO cheese at numbers often exceeding the Italian tolerance threshold represents an important risk factor. SIGNIFICANCE AND IMPACT OF THE STUDY: The high frequency of contamination of Monte Veronese PDO cheese and, expectedly, similar typical productions from raw milk, by enterotoxigenic Staph. aureus imposes a tighter hygienic control in the earlier manufacturing phases. PMID- 17868314 TI - Production and partial characterization of cellulase free xylanase by Bacillus subtilis C 01 using agriresidues and its application in biobleaching of nonwoody plant pulps. AB - AIMS: To optimize the solid-state cultivation conditions for xylanase production using agriresidues and testing the biobleaching efficiency of xylanase on nonwoody plant fibre materials. METHODS AND RESULTS: An extracellular cellulase free xylanase was produced from Bacillus subtilis C 01 using various inexpensive substrates under solid-state cultivation. High level of xylanase production (135 IU gds(-1)) was observed when grown on wheat bran followed by maize powder (50 IU gds(-1)). The maximum xylanase (136 IU gds(-1)) production was occurred in wheat bran-to-moisture ratio of 1 : 1 at 72 h. The xylanase pretreated pulp samples of banana, silk cotton and cotton showed an increased brightness of 19.6, 11.6 and 7.9%, respectively. CONCLUSIONS: The enzyme-aided biobleaching results indicate that the xylanase has potential application in enhancing the brightness of nonwoody plant fibre pulp. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on biobleaching of banana fibres, silk cotton and cotton pulps using xylanase. The biobleaching results of secondary fibres are promising and can be transferred to paper mills, which utilize nonwoody plant fibres as a raw material for paper production. PMID- 17868315 TI - Production of inulinase by Xanthomonas campestris pv phaseoli using onion (Allium cepa) and garlic (Allium sativum) peels in solid state cultivation. AB - AIMS: To access inulinase production by Xanthomonas campestris pv phaseoli using the submerged and solid state cultivation (SSC) methods. METHODS AND RESULTS: Various carbon sources, inulin-rich solid substrates and pure synthetic inulin were tested for their efficiency in inulinase induction. The highest inulinase production (17.42 IU ml(-1)) in submerged cultures of X. campestris was observed with inulin as a carbon source with an initial pH, temperature and agitation of 7.0, 37 degrees C and 150 rev min(-1) respectively. Among the various substrates, garlic peels (117 IU gds(-1)) and onion peels (101 IU gds(-1)) were found to be the best for inulinase production. CONCLUSION: The inulinase production level of X. campestris was 6.7-fold higher in garlic and 5.8-fold in onion, under optimized SSC conditions compared with the submerged culture. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on inulinase production from garlic and onion peels by X. campestris using SSC. SSC is an efficient method for inulinase production by X. campestris for commercial applications. PMID- 17868316 TI - Cytidine deamination assay to differentiate Staphylococcus aureus from other staphylococci. AB - AIMS: Adoption of the property of cytidine (cytosine-beta-d-riboside) deamination in staphylococci to distinguish Staphylococcus aureus from other staphylococci. METHODS AND RESULTS: A total of 560 staphylococcal strains were examined. The test demonstrated a sensitivity of 97.1% and a specificity of 98.8%. Of the 249 S. aureus strains (115 oxacillin-resistant) 58 strains were coagulase-negative S. aureus and another 16 strains were clumping factor-negative S. aureus. The 74 deficient S. aureus strains were identified by 16S rRNA gene sequencing and further investigated by spa typing and 13 spa types were found. CONCLUSIONS: The cytidine deaminase test (CDT) is useful especially for distinguishing coagulase- and clumping factor-negative S. aureus from other staphylococci and the results correlated well with 16S rRNA sequencing and the polymerase chain reaction (PCR) amplification of the nuc gene. SIGNIFICANCE AND IMPACT OF THE STUDY: Cytidine deamination assay differentiates S. aureus from other staphylococci. This method is fast (6 h) and reliable in distinguishing between non-S. aureus and the defective (coagulase-negative, clumping factor-negative) S. aureus isolates which could have major consequences for therapy. PMID- 17868317 TI - Identification of vip3A-type genes from Bacillus thuringiensis strains and characterization of a novel vip3A-type gene. AB - AIMS: To search for novel Vip3A proteins for controlling insect pests. METHODS AND RESULTS: A pair of universal primers was designed based on the conserved regions of five vip3A genes. Amplified products were digested with the HindIII and EcoR enzymes so as to confirm different restriction fragment length polymorphism (RFLP) patterns used to identify vip3A-type genes. The vip3A gene types of 606 Bacillus thuringiensis strains were screened and three patterns of RFLP were successfully identified. Two novel vip3A genes were found and one of these, vip3Aa19, was further characterized and its product was confirmed toxic to Spodoptera exigua, Helicoverpa armigera and Plutella xylostella larvae. Partial sequences of another novel vip3A-type gene were obtained that shared 83% homology with that of the vip3Af1 gene. CONCLUSIONS: A polymerase chain reaction (PCR) RFLP system we developed could be used for identifying novel vip3A-genes from B. thuringiensis strains. A novel Vip3A protein was found to have a broader insecticidal spectrum. SIGNIFICANCE AND IMPACT OF THE STUDY: The reported method is a powerful tool to find novel Vip3A proteins from large-scale B. thuringiensis strains. The novel Vip3A protein may be used to control insect pests or resistant insect pests by constructing genetically engineered strains or transgenic plants. PMID- 17868318 TI - An efficient purification and fractionation of genomic DNA from soil by modified troughing method. AB - AIMS: The aim of this study was to utilize a modified troughing method for purification of large genomic DNA obtained from microbiota in natural environment and for fractionation of genomic DNA into many size ranges that facilitates construction of metagenomic library. METHODS AND RESULTS: Genomic DNA extracted from soil or termite gut was purified by the modified troughing method which utilized gel electrophoresis in the presence of 30% PEG8000. The method performed better than various purification kits and allowed no significant loss in the amount of DNA recovered. In addition, the efficiency of the modified troughing method for DNA size fractionation was investigated. DNA size fractionation was achieved with repetitive rounds of electrophoresis and DNA collection to obtain DNA with many size ranges. CONCLUSIONS: The modified troughing method is a simple and efficient method for purification of genomic DNA and for DNA size fractionation. SIGNIFICANCE AND IMPACT OF THE STUDY: The modified troughing method is a straightforward and inexpensive technique readily available for anyone working with environmental genomic DNA. It facilitates cloning of genomic DNA and enhances rapid discovery of useful bioactive compounds from microbial resources. PMID- 17868319 TI - Induction of apoptosis in Caco-2 and HT-29 human intestinal epithelial cells by enterohemolysin produced by classic enteropathogenic Escherichia coli. AB - AIMS: Detect the cytotoxic effects of the Enterohemolysin from enteropathogenic Escherichia coli C3888 (O 26: H-) on Caco 2 and HT-29-human epithelial intestinal cells. METHODS AND RESULTS: The Caco 2 and HT-29 cells, which were treated with Enterohemolysin (EHly) within 10-15 min, became round, lost attachment to substrate, showed extensive surface blebbing, nucleus shrank, and the chromatin became more compact. After 10 min of exposure to the EHly, the cells showed lactate dehydrogenase (LDH) leakage and reduction of mitochondrial activity. The cells showed disorganization of the actin fibers at 15 min. The death of these human epithelial intestinal cells by apoptosis was confirmed by annexin V. CONCLUSIONS: Enterohemolysin induced apoptosis on human epithelial intestinal cells. SIGNIFICANCE AND IMPACT OF THE STUDY: The finding of EHly cytotoxic activity suggests the involvement of this hemolysin in the (Enteropathogenic Escherichia coli) EPEC infection mechanism and may facilitate the understanding of the diarrhea caused by EPEC. PMID- 17868320 TI - Inhibition of cortical astrocyte differentiation by Hes6 requires amino- and carboxy-terminal motifs important for dimerization and phosphorylation. AB - Hairy/Enhancer of split (Hes) 6 is a basic helix-loop-helix protein that interacts with the transcriptional co-repressor, Groucho, and antagonizes the neural functions of the Notch pathway. More specifically, mouse Hes6 regulates cerebral corticogenesis by promoting neurogenesis and suppressing astrocyte differentiation. The molecular mechanisms underlying the anti-astrogenic function of Hes6 are poorly defined. Here we describe studies aimed at testing whether Hes6 inhibits astrocyte differentiation by antagonizing the transcription repression activity of Notch-activated Hes family members like Hes1. It is reported that Hes6 preferentially forms homodimers. Heterodimerization with Hes1 is antagonized in part by a conserved N-terminal patch of negatively charged residues. Mutation of this motif enhances heterodimerization with Hes1 and increases Hes6 ability to antagonize Hes1-mediated transcriptional repression. However, this mutation does not increase, but instead decreases, the anti astrogenic activity of Hes6. It is shown further that Hes6 harbors a second conserved sequence, a C-terminal SPXXSP motif. This sequence is phosphorylated by the mitogen activated protein kinase pathway and its mutation disrupts the anti astrogenic activity of Hes6 without affecting its ability to suppress Hes1. Together, these observations suggest that Hes6 homodimers regulate astrocyte differentiation through mechanisms that depend on the phosphorylation of Hes6 C terminal domain but are independent of its ability to suppress Hes1-mediated transcriptional repression. PMID- 17868321 TI - Minocycline decreases in vitro microglial motility, beta1-integrin, and Kv1.3 channel expression. AB - Minocycline is a semisynthetic, tetracycline derivative that exerts anti inflammatory and neuroprotective effects unrelated to its anti-microbial action. We have previously shown that minocycline prevented peripheral nerve injury induced mechanical allodynia. Minocycline's mechanisms of action as a neuroprotective and anti-allodynic agent are unknown. In response to injury, microglia become activated, proliferate, and migrate. Resting microglia express voltage-dependent inward K(+) currents and blocking Kv1.3 channels has been shown to inhibit microglial-mediated neuronal death. We investigated the effect of minocycline on the expression of Kv channels, cell motility, and beta-integrin expression using primary rat cortical microglia, transwell assays, and by flow cytometry. Minocycline significantly reduced microglial migration to cellular debris, astrocyte-conditioned medium, ADP, and algesic mediators and significantly reduced the expression of CD29 (beta(1)-integrin) but not CD18 (beta(2)-integrin). Minocycline reduced the effect of extracellular potassium and later decreased microglial Kv1.3 expression. In summary, we uncovered a novel effect of minocycline that demonstrates this agent decreases microglial beta(1) integrin expression, which leads to inhibition of motility. We propose an in vivo model whereby reduced microglial trafficking to injured neurons following nerve injury decreases the release of proinflammatory mediators into the synaptic milieu, preventing neuronal sensitization, the pathological correlate to chronic pain. PMID- 17868322 TI - Differential regulation of the Cdk5-dependent phosphorylation sites of inhibitor 1 and DARPP-32 by depolarization. AB - While cyclin-dependent kinase 5 (Cdk5) is of growing importance to neuronal signaling, its regulation remains relatively unexplored. Examination of the mechanism by which NMDA modulates the phosphorylation of protein phosphatase inhibitor-1 at Ser6 and Ser67 and dopamine- and cAMP-regulated phosphoprotein M(r) 32 000 at Thr75 revealed that generalized depolarization, rather than specific activation of NMDA receptors, was sufficient to induce decreases in these Cdk5 sites. Although no evidence for the involvement of the Cdk5 cofactors p35 or p39, or for L- and T-type voltage-gated Ca(2+) channels, was found, evaluation of the role of phosphatases and extracellular cations revealed differential regulation of the three sites. NMDA-induced decreases in the phosphorylation of Thr75 of dopamine- and cAMP-regulated phosphoprotein M(r) 32 000 required protein phosphatase 1/2A activity and extracellular Ca(2+). In contrast, the effects on Ser6 and Ser67 of inhibitor-1 were not cation specific; either Na(+) or Ca(2+) sufficed. Furthermore, while the decrease in phosphorylation of Ser6 was partially dependent on protein phosphatase 2B, that of Ser67 was independent of the major protein serine/threonine phosphatases, likely indicating the presence of a pathway by which NMDA inhibits Cdk5 activity. Thus, in the striatum the regulation of phosphorylation of Cdk5-dependent sites by NMDA occurs through multiple distinct pathways. PMID- 17868323 TI - Increased expression of lysosomal acid phosphatase in CLN3-defective cells and mouse brain tissue. AB - Juvenile neuronal ceroid lipofuscinosis (Batten disease) is a neurodegenerative disorder caused by defective function of the lysosomal membrane glycoprotein CLN3. The activity of the lysosomal acid phosphatase (LAP/ACP2) was found to be significantly increased in the cerebellum and brain stem of Cln3-targeted mice during the early stages of postnatal life. Histochemical localization studies revealed an increased LAP/ACP2 staining intensity in neurons of the cerebral cortex of 48-week-old Cln3-targeted mice as compared with controls. Additionally, the expression of another lysosomal membrane protein LAMP-2 was increased in all brain areas. Knockdown of CLN3 expression in HeLa cells by RNA interference also resulted in increased LAP/ACP2 and LAMP-2 expression. Finally in fibroblasts of two juvenile neuronal ceroid lipofuscinosis patients elevated levels of LAP/ACP2 were found. Both activation of gene transcription and increased protein half-life appear to contribute to increased LAP/ACP2 protein expression in CLN3-deficient cells. The data suggest that lysosomal dysfunction and accumulation of storage material require increased biogenesis of LAP/ACP2 and LAMP-2 positive membranes which makes LAP/ACP2 suitable as biomarker of Batten disease. PMID- 17868324 TI - Interrupting activator protein-1 signaling in conscious rats can modify neuropeptide Y gene expression and feeding behavior of phenylpropanolamine. AB - The mechanism for phenylpropanolamine (PPA)-induced anorexia has been attributed to its inhibitory action on hypothalamic neuropeptide Y (NPY), an orexigenic agent abundant in the brain. However, molecular mechanisms behind this effect are not well known. In this study, we investigated whether activator protein-1 (AP-1) signaling was involved. Rats were daily treated with PPA for 4 days. Changes in hypothalamic NPY, c-fos, c-jun, superoxide dismutase (SOD)-1, and SOD-2 mRNA contents were measured and compared. Results showed that c-fos and c-jun mRNA levels were increased following PPA treatment, which were relevant to a reduction in NPY mRNA level. To further determine if c-fos/c-jun genes were involved in PPA anorexia, infusions of antisense oligonucleotide into cerebroventricle were performed before daily PPA treatment in freely moving rats. Results showed that either c-fos or c-jun knock down could block PPA anorexia and restore NPY mRNA content to normal level. It is suggested that AP-1 signaling may participate in the central regulation of PPA-mediated appetite suppression via the modulation of NPY gene expression. Moreover, this modulation might be partly because of the neuroprotective effect of AP-1 since SOD gene was activated during PPA treatment. PMID- 17868325 TI - Neurexin Ibeta and neuroligin are localized on opposite membranes in mature central synapses. AB - Synaptogenesis requires formation of trans-synaptic complexes between neuronal cell-adhesion receptors. Heterophilic receptor pairs, such as neurexin Ibeta and neuroligin, can mediate distinct intracellular signals and form different cytoplasmic scaffolds in the pre- and post-synaptic neuron, and may be particularly important for synaptogenesis. However, the functions of neurexin and neuroligin depend on their distribution in the synapse. Neuroligin has been experimentally assigned to the post-synaptic membrane, while the localization of neurexin remains unclear. To study the subcellular distribution of neurexin Ibeta and neuroligin in mature cerebrocortical synapses, we have developed a novel method for the physical separation of junctional membranes and their direct analysis by western blotting. Using urea and dithiothreitol, we disrupted trans synaptic protein links, without dissolving the lipid phase, and fractionated the pre- and post-synaptic membranes. The purity of these fractions was validated by electron microscopy and western blotting using multiple synaptic markers. A quantitative analysis has confirmed that neuroligin is localized strictly in the post-synaptic membrane. We have also demonstrated that neurexin Ibeta is largely (96%) pre-synaptic. Thus, neurexin Ibeta and neuroligin normally form trans synaptic complexes and can transduce bidirectional signals. PMID- 17868326 TI - Spinal cord mitochondria display lower calcium retention capacity compared with brain mitochondria without inherent differences in sensitivity to cyclophilin D inhibition. AB - The mitochondrial permeability transition (mPT) is a potential pathogenic mechanism in neurodegeneration. Varying sensitivity to calcium-induced mPT has been demonstrated for regions within the CNS possibly correlating with vulnerability following insults. The spinal cord is selectively vulnerable in e.g. amyotrophic lateral sclerosis and increased mPT sensitivity of mitochondria derived from the spinal cord has previously been demonstrated. In this study, we introduce whole-body hypothermia prior to removal of CNS tissue to minimize the effects of differential tissue extraction prior to isolation of spinal cord and cortical brain mitochondria. Spinal cord mitochondria were able to retain considerably less calcium when administered as continuous infusion, which was not related to a general increased sensitivity of the mPT to calcium, its desensitization to calcium by the cyclophilin D inhibitor cyclosporin-A, or to differences in respiratory parameters. Spinal cord mitochondria maintained a higher concentration of extramitochondrial calcium during infusion than brain mitochondria possibly related to an increased set-point concentration for calcium uptake. A hampered transport and retention capacity of calcium may translate into an increased susceptibility of the spinal cord to neurodegenerative processes involving calcium-mediated damage. PMID- 17868327 TI - Timing of potential and metabolic brain energy. AB - The temporal relationship between cerebral electro-physiological activities, higher brain functions and brain energy metabolism is reviewed. The duration of action potentials and transmission through glutamate and GABA are most often less than 5 ms. Subjects may perform complex psycho-physiological tasks within 50 to 200 ms, and perception of conscious experience requires 0.5 to 2 s. Activation of cerebral oxygen consumption starts after at least 100 ms and increases of local blood flow become maximal after about 1 s. Current imaging technologies are unable to detect rapid physiological brain functions. We introduce the concepts of potential and metabolic brain energy to distinguish trans-membrane gradients of ions or neurotransmitters and the capacity to generate energy from intra- or extra-cerebral substrates, respectively. Higher brain functions, such as memory retrieval, speaking, consciousness and self-consciousness are so fast that their execution depends primarily on fast neurotransmission (in the millisecond range) and action-potentials. In other words: brain functioning requires primarily maximal potential energy. Metabolic brain energy is necessary to restore and maintain the potential energy. PMID- 17868328 TI - Expression level and activity profile of membrane bound guanylate cyclase type 2 in rod outer segments. AB - Rod and cone cells of the mammalian retina harbor two types of a membrane bound guanylate cyclase (GC), rod outer segment guanylate cyclase type 1 (ROS-GC1) and ROS-GC2. Both enzymes are regulated by small Ca(2+)-binding proteins named GC activating proteins that operate as Ca2+ sensors and enable cyclases to respond to changes of intracellular Ca2+after illumination. We determined the expression level of ROS-GC2 in bovine ROS preparations and compared it with the level of ROS GC1 in ROSs. The molar ratio of a ROS-GC2 dimer to rhodopsin was 1 : 13 200. The amount of ROS-GC1 was 25-fold higher than the amount of ROS-GC2. Heterologously expressed ROS-GC2 was differentially activated by GC-activating protein 1 and 2 at low free Ca2+ concentrations. Mutants of GC-activating protein 2 modulated ROS GC2 in a manner different from their action on ROS-GC1 indicating that the Ca2+ sensitivity of the Ca2+ sensor is controlled by the mode of target-sensor interaction. PMID- 17868329 TI - Chronic exposure to sub-lethal beta-amyloid (Abeta) inhibits the import of nuclear-encoded proteins to mitochondria in differentiated PC12 cells. AB - Studies on amyloid beta (Abeta|), the peptide thought to play a crucial role in the pathogenesis of Alzheimer's disease, have implicated mitochondria in Abeta mediated neurotoxicity. We used differentiated PC12 cells stably transfected with an inducible green fluorescent protein (GFP) fusion protein containing an N' terminal mitochondrial targeting sequence (mtGFP), to examine the effects of sub lethal Abeta on the import of nuclear-encoded proteins to mitochondria. Exposure to sub-lethal Abeta(25-35) (10 mumol/L) for 48 h inhibited mtGFP import to mitochondria; average rates decreased by 20 +/- 4%. Concomitant with the decline in mtGFP, cytoplasmic mtGFP increased significantly while mtGFP expression and intramitochondrial mtGFP turnover were unchanged. Sub-lethal Abeta(1-42) inhibited mtGFP import and increased cytoplasmic mtGFP but only after 96 h. The import of two endogenous nuclear-encoded mitochondrial proteins, mortalin/mtHsp70 and Tom20 also declined. Prior to the decline in import, mitochondrial membrane potential (mmp), and reactive oxygen species levels were unchanged in Abeta treated cells versus reverse phase controls. Sustained periods of decreased import were associated with decreased mmp, increased reactive oxygen species, increased vulnerability to oxygen-glucose deprivation and altered mitochondrial morphology. These findings suggest that an Abeta-mediated inhibition of mitochondrial protein import, and the consequent mitochondrial impairment, may contribute to Alzheimer's disease. PMID- 17868330 TI - Activation of peroxisome proliferator-activated receptor alpha by dietary fish oil attenuates steatosis, but does not prevent experimental steatohepatitis because of hepatic lipoperoxide accumulation. AB - BACKGROUND AND AIM: Non-alcoholic fatty liver disease is the result of an imbalance in hepatic lipid partitioning that favors fatty acid synthesis and storage over fatty acid oxidation and triglyceride secretion. The progressive, inflammatory disorder of steatohepatitis can be prevented or reversed by correcting this lipid imbalance by activating peroxisome proliferator-activated receptor (PPAR) alpha, a transcription factor which regulates fatty acid oxidation. n-3 polyunsaturated fatty acids (PUFA), such as those found in fish oil (FO), are naturally occurring PPARalpha ligands which also suppress lipid synthesis. METHODS: We tested the role of dietary activation of PPARalpha by feeding mice a n-3 PUFA-enriched FO diet in the methionine and choline deficient (MCD) model of steatohepatitis. Results were compared with mice fed the corresponding diet supplemented with monounsaturated fatty acids as olive oil (OO). RESULTS: As expected, FO feeding led to robust hepatic PPARalpha activation in control mice, and decreased expression of genes involved with fatty acid synthesis. Such lipolytic gene expression profile was also clearly evident in FO MCD-fed mice, and was associated with reduced hepatic lipid accumulation in comparison with mice fed OO MCD diet. FO feeding in control mice also caused marked hepatic accumulation of lipoperoxides compared with OO and chow-fed mice. This was further exacerbated in FO MCD-fed animals, which developed steatohepatitis characterized by mild steatosis and moderate inflammation in comparison with OO MCD-fed mice; such inflammatory recruitment was not related to NF-kappaB activation or enhanced cyclooxygenase-2 activity. CONCLUSIONS: Feeding an n-3 PUFA-enriched diet activated PPARalpha and suppressed hepatic de novo lipogenesis, but failed to prevent development of steatohepatitis in the presence of methionine and choline deficiency. Instead, the very high levels of hepatic lipoperoxides may have abrogated the protection that would otherwise be conferred by PPARalpha activation, and could also be responsible for lipotoxic hepatocellular injury and inflammatory recruitment. PMID- 17868331 TI - Congenital veno-venous malformations of the liver: widely variable clinical presentations. AB - BACKGROUND AND AIM: Congenital portosystemic veno-venous malformations are rare abnomalities that often remain undiagnosed. Typically they are classified by their anatomical characteristics according to Morgan (extrahepatic, Abernethy malformations type Ia,b and II) and Park (intrahepatic, types 1-4). However, their clinical presentation is less dependent on the anatomical type. METHOD: We reviewed the clinical characteristics of six cases drawn from our files (from 1970 to 2006). RESULTS: One patient, a 25-year-old male, had extrahepatic shunting whereby the liver receives only arterial blood because the portal vein (PV) connects with the inferior caval vein (ICV) (Abernethy Ib); he presented with episodes of jaundice and pruritus. Three patients had extrahepatic shunting with patent intrahepatic portal veins, but with shunting of splenomesenterial blood towards the ICV (Abernethy II); these included a 66-year-old male with hepatic encephalopathy, a 17-year-old female with (porto?-)pulmonary hypertension without portal hypertension, and a 33-year-old female with epidsodes of acute pain secondary to spontaneous bleeding within a primary liver tumor. Two patients had intrahepatic shunting; these included an 8-year-old boy who was diagnosed incidentally during work-up for abnormal liver enzymes with a communication between right PV and ICV (Park type 1), and a 59-year-old male with multiple PV ICV-shunts in several liver segments (Park, type 4) who presented with hepatic encephalopathy. CONCLUSION: Patients often present with signs of hepatic shunting (encephalopathy, pulmonary hypertension, hepatopulmonary syndrome, and/or hypoglycemia) with relative sparing of the synthetic liver function in the absence of portal hypertension. Some shunts present with space-occupying lesions (focal nodular hyperplasia, hepatocellular carcinoma, nodular regenerative hyperplasia, etc.) or biliary atresia. Finally, some cases are detected incidentally. PMID- 17868332 TI - Prophylaxis with mesna prevents oxidative stress induced by ischemia reperfusion in the intestine via inhibition of nuclear factor-kappaB activation. AB - BACKGROUND AND AIM: Mesna (2-mercaptoethane-sulfonate) has been shown to attenuate oxidative injury induced by ischemia reperfusion (I/R) in the kidneys, the liver, and the intestine; however, its mechanism of action has not been fully elucidated. We sought to determine a prophylactic administration schedule of mesna that would confer optimal antioxidant protection on the intestinal mucosa following I/R and to investigate whether mesna's action is mediated via inhibition of nuclear factor-kappaB (NF-kappaB) activity. METHODS: Wistar rats were subjected to one of the following: (a) induction of 30 min ischemia followed by 60 min reperfusion (I30/R60) of the intestine, (b) pretreatment with intraperitoneal or oral mesna at various time- and dose- administration schedules plus I30/R60, (c) sham operation, (d) no operation (controls), or (e) oral mesna alone. At the end of the reperfusion period or at various time points after mesna alone administration, the oxidative state of the intestinal mucosa was assessed in terms of glutathione to glutathione disulfide ratio, malondialdehyde concentration, and superoxide dismutase activity. In addition, NF-kappaB activity in the intestinal mucosa was assessed immunohistochemically in the oral mesna plus I/R and in the oral mesna alone groups. RESULTS: Sham operation caused mild stress, while I/R caused substantial oxidative stress in the intestinal mucosa. Mesna pretreatment had an antioxidant effect which varied from attenuation to prevention of oxidative stress. Over the two routes of administration, the oral proved to be more effective and had a time- and dose- dependent effect. The antioxidant action of mesna was not related to enhancement of the intestinal mucosa oxidative state. Furthermore, I/R induced NF-kappaB activation in the intestinal mucosa which was inhibited by mesna pretreatment. In the absence of oxidative damage, mesna led to downregulation of activated NF-kappaB. CONCLUSIONS: Prophylaxis with mesna prevents oxidative stress induced by I/R in the intestine via inhibition of NF-kappaB activation. PMID- 17868333 TI - Role of phosphatidylcholine saturation in preventing bile salt toxicity to gastrointestinal epithelia and membranes. AB - BACKGROUND AND AIM: The mechanism which protects the biliary and intestinal mucosa from the detergent properties of bile acids is not fully understood. We employed three contrasting in vitro model systems (human red blood cells, polarized intestinal [Caco-2] cells, and synthetic liposomes), to compare the efficacy of saturated and unsaturated phosphatidylcholine (PC) to protect cells and membranes from bile salt injury. METHODS: Hemolysis of red blood cells, electrical resistance across confluent monolayers of Caco-2 cells, and disruption of synthetic PC liposomes were assessed after incubation with varying concentrations of bile salt (sodium deoxycholate) alone or in the presence of saturated or unsaturated PC. RESULTS: The hemolytic activity of deoxycholate on red blood cells was observed at > or =2 mM, and could be blocked by equimolar concentration or greater of both saturated or unsaturated PC. In contrast, exposure of Caco-2 cells to deoxycholate at > or =0.8 mM induced a maximal decrease in resistance, which was reversed by > or =0.8 mM unsaturated PC or 5 mM saturated PC. Similarly, synthetic liposomes were permeabilized by 0.8 mM deoxycholate and were protected by a lower concentration of unsaturated PC (2 mM) than saturated (5 mM). CONCLUSIONS: Cells can show variable resistance to bile salt toxicity. Extracellular PC, especially in the unsaturated state, can directly protect cell and artificial membranes from bile salt injury. These findings support a role for biliary PC in the formation of mixed micelles that have low cytotoxic properties. PMID- 17868334 TI - Interstrain differences in susceptibility to non-alcoholic steatohepatitis. AB - BACKGROUND AND AIM: The pathophysiological mechanisms leading to the development of non-alcoholic steatohepatitis (NASH) remain unclear. There are differences in the susceptibility to NASH between the different species and sexes. The investigation of the precise mechanism of interstrain differences may provide new means by which the pathophysiological mechanisms of NASH may be understood. METHODS: C57BL/6N and C3H/HeN mice were administered a methionine- and choline deficient (MCD) diet to establish a dietary model of NASH. RESULTS: An elevation of the serum alanine aminotransferase and increased infiltration of inflammatory cells were predominant in C57BL/6N mice at 8 weeks. The increase in the steatosis and lipid contents in the liver was greater in C57BL/6N mice than in C3H/HeN mice. The indices of lipid peroxidation demonstrated by F2-isoprostanes or 8 hydroxy-2'-deoxyguanosine also increased in the livers of C57BL/6N mice. Furthermore, Sirius red staining revealed an increase in the degree of fibrosis in C57BL/6N mice given the MCD diet. As a result, the C57BL/6N strain had a higher susceptibility to NASH than the C3H/HeN mice. The carnitine palmitoyltransferase 1A (in beta-oxidation) mRNA and mitochondrial 3-hydroxy-3 methylglutaryl-CoA synthase 2 (in ketogenesis) mRNA were downregulated in the C57BL/6N mice in comparison with C3H/HeN mice. There were no differences in the expression of microsomal triglyceride transfer protein or sterol regulatory element binding protein 1 between the C57BL/6N and C3H/HeN mice. CONCLUSION: There were interstrain differences in susceptibility to NASH observed in a rodent dietary model. Further evaluations of the precise molecular mechanism of this interstrain difference may provide some indications of the pathophysiological mechanisms of NASH in humans. PMID- 17868336 TI - What prognostic factors are important for resected intrahepatic cholangiocarcinoma? AB - BACKGROUND AND AIM: Our aim was to evaluate the predictive factors for survival and disease-free survival of patients with resected intrahepatic cholangiocarcinoma (ICC). METHODS: Between October 1994 and 2005, 97 patients with ICC underwent curative hepatic resection. The tumors in 97 patients were reviewed retrospectively to examine the prognosis of ICC. RESULTS: The 1-, 3- and 5-year survival rates were 74.9%, 51.8% and 31.1%, respectively. The 1-, 3- and 5 year disease-free survival rates were 21.3%, 6.4% and 2.1%, respectively. Univariate analysis showed that tumor size, tumor number, the gross type, resection margin status, T-stage and lymph node involvement were significant prognostic factors. Multiple tumors and cancer cells in the resection margin were found in multivariate analysis to be significantly related to the prognosis. In the multivariate analysis disease free survival was poor for the patients with a large tumor, multiple lesions, a high CA 19-9 level, cancer in the resection margin, advanced T-stage and lymph node involvement. CONCLUSIONS: The overall 5 year survival rate of ICC was 31.1%. Multiple intrahepatic lesions were a sign of a poor prognosis for ICC. Better survival could be achieved by curative resection with a tumor-free margin. PMID- 17868335 TI - Cytoprotective effect of tauroursodeoxycholate on hepatocyte apoptosis induced by peroxisome proliferator-activated receptor gamma ligand. AB - BACKGROUND AND AIM: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands inhibit cell growth and induce apoptosis in various cancer cells. Bile acids are also known to cause hepatocyte apoptosis through nuclear receptor mediated mechanisms. The aim of this study was to examine the effect of two different bile acid species on the inhibitory action of PPARgamma in cell growth with paying attention to the role of the mitogen-activated protein kinase pathway as an underlying mechanism. METHODS: Immortalized human hepatocytes (OUMS-29) and hepatoma cells (HepG2 and Huh7) were incubated with troglitazone (TGZ), a PPARgamma ligand with or without pre-incubation of either hydrophobic glycochenodeoxycholate (GCDC) or hydrophilic tauroursodeoxycholate (TUDC). RESULTS: TGZ induced cell apoptosis in all cell types, resulting in the reduction of cell viability. While pre-incubation with GCDC enhanced the apoptotic effects of TGZ, TUDC significantly attenuated it. Both bile acids enhanced p38 and c-Jun N-terminal kinase (JNK) phosphorylation in a similar way, whereas there was more drastic enhancement of extracellular signal-regulated kinase (ERK) 1/2 phosphorylation in the presence of TUDC compared to GCDC. In addition, ERK inhibitors suppressed the action of TUDC against apoptotic effect of TGZ. CONCLUSION: This study demonstrates that TUDC exhibits anti-apoptotic and cytoprotective effects against TGZ-induced cell apoptosis, presumably through the ERK signaling pathway. We speculate that the administration of TUDC might be one of the potential strategies for the hepatotoxicity caused by TGZ. PMID- 17868337 TI - The attitude and knowledge of cervical cancer by Cameroonian women; a clinical survey conducted in Maroua, the capital of Far North Province of Cameroon. AB - This study was conducted to assess the knowledge, attitudes, and assumption of cervical cancer by women living in Maroua, the capital of the Far North Province of Cameroon. In a 1-month period, 171 women were surveyed as to their socioeconomic status, sexual habits, prior knowledge of cervical cancer, its prevention, and their attitudes toward cervical cancer. Of 171 women, 48 (28%) had prior knowledge of cervical cancer; they were classified as the "aware group" compared with 123 of 171 (72%) women who were uninformed about cervical cancer and they were classified as the "unaware group" (UG). The UG of women tended to be single mothers, illiterate, housewives, and had their first child before the age of 20 (P < 0.005). Despite the awareness of cervical cancer by 28% of women, only a minority of them, 4 of 48 (8.3%), underwent a preventative screening test. Only 71 of 171 (41.5%) women stated that they would be having a screening test in the future. The awareness of cervical cancer by women in Cameroon is still inadequate. Thus, to avoid deaths from cervical cancer, a curable and preventable disease, the need of an aggressive campaign to make Cameroonian women aware of cervical cancer and its prevention is needed. PMID- 17868338 TI - Characteristics of recurrence in adult-type granulosa cell tumor. AB - Granulosa cell tumor (GCT) of the ovary is a very rare neoplasm, which is characterized by an indolent clinical course. Thus, the clinical characteristics, optimal treatment, and follow-up protocols are not well established. The goal of this study is to evaluate clinical findings, prognostic factors, and recurrent features of GCT in Korean patients. Between 1987 and 2005, 42 cases of GCT were diagnosed in our institution. There were 35 cases showing adult-type GCT, which were available for evaluation. All charts were reviewed, and the clinical data along with treatment results were retrospectively studied. Statistical analyses were performed for risk factors of recurrence and disease-free survival. GCT accounted for 3% of all ovarian malignancies in our institution during the study period. The median age was 45 years (range, 24-68 years). Abdominal and hormone related symptoms were the main causes of first presentation. There were eight cases of recurrence including two cases of disease-related deaths during the median follow-up period of 177 months (range, 8-212 months). Factors affecting the recurrence involved residual tumor and stage, but residual tumor was the only significant factor of recurrence in multivariate analysis. The median time to relapse was 75 months (range, 55-137 months), and the liver was the most common extra-pelvic metastatic site followed by the intestine. Continuous long-term follow-up with pelvic and whole-abdominal surveillance is absolutely required. Active management including complete tumorectomy is the most important treatment modality in both primary surgeries and recurrent cases. PMID- 17868339 TI - Preoperative serum CA125 levels do not predict suboptimal cytoreductive surgery in epithelial ovarian cancer. AB - The objective is to assess the ability of preoperative serum CA125 levels to identify patients at high risk of suboptimal cytoreductive surgery for epithelial ovarian cancer (EOC). One hundred and thirty-two women diagnosed with EOC between 1998 and 2004, who had serum CA125 levels measured preoperatively and received primary cytoreductive surgery, were retrospectively evaluated. The value of CA125 and patient and disease characteristics to predict suboptimal cytoreduction were determined, and a prognostic scoring system, based on statistically significant variables, was created. Optimal cytoreduction was achieved in 42.7% of the women with FIGO stage III/IV EOC. The optimal cutoff point of preoperative CA125 to predict surgical outcome in this group was 330 U/mL (sensitivity 80.0%; specificity 41.5%). The area under the receiver-operating characteristic curve (AUC) for preoperative CA125 predicting suboptimal surgery in FIGO stage III/IV was 0.576 (P = 0.617). Preoperative radiologic amount of ascites and weight loss (ie, >or=10% in the last 6 months before diagnosis) were independent prognostic factors for suboptimal cytoreduction, showing an AUC of 0.76 (P < 0.001) in women with FIGO stage III/IV. A prognostic scoring system showed that the chance of suboptimal surgery was 84.6% in FIGO stage III/IV when both these factors are present preoperatively. The role of CA125 levels predicting suboptimal cytoreduction seems questionable. Instead, women with considerable weight loss and a gross amount of ascites have a higher risk of suboptimal cytoreduction. These patients may be candidates for neoadjuvant chemotherapy. PMID- 17868340 TI - Cell detachment modulates TRAIL resistance in ovarian cancer cells by downregulating the phosphatidylinositol 3-kinase/Akt pathway. AB - TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a potent inducer of apoptosis but many ovarian cancer cells display intrinsic resistance to TRAIL. The molecular determinants regulating TRAIL sensitivity in these resistant tumor cells are still incompletely understood. We observed that cell detachment enhances TRAIL-induced apoptosis in two TRAIL-resistant ovarian cancer cell lines. This process was accompanied by an increase of caspase activation, which could be blocked by caspase-8 inhibitor IETD. Cell detachment inhibited Akt phosphorylation. Phosphatidylinositol 3-kinase inhibition by LY294002 also enhanced TRAIL-induced apoptosis. Further decreased Akt activity by LY294002 in detached cells translated to increased cell death after TRAIL treatment. Our data indicate that cell detachment enhances TRAIL-induced killing by decreasing Akt activity in TRAIL-resistant ovarian carcinoma cells and suggest that Akt inhibition primes TRAIL-resistant cells to TRAIL-induced apoptosis. PMID- 17868341 TI - Analysis of human papillomavirus and Epstein-Barr virus infection and aberrant death-associated protein kinase methylation in high-grade squamous intraepithelial lesions. AB - This study was conducted to investigate the presence of Epstein-Barr virus (EBV) and human papillomavirus (HPV) and the promoter methylation status of the death associated protein kinase (DAPK) gene in high-grade intraepithelial lesions. Viral infection was analyzed using polymerase chain reaction (PCR), and promoter methylation status was evaluated using chemical modification by sodium bisulfite followed by PCR. A total of 24 samples were studied. HPV was detected in 16.6%, EBV in 16.6%, and HPV/EBV coinfection in 16.6%. No virus infection was detected in 50% of the samples studied. DAPK promoter methylation was observed in 29.2% of the analyzed samples. There was no significant correlation between DAPK methylation and viral infection. DAPK methylation was detected in 28% of HPV positive lesions, in 28% of HPV- and EBV-positive lesions, and in 44% (3/7) of the samples without viral infection. There was no observed methylation in samples with isolated EBV infection. In DAPK unmethylated samples, HPV infection was found in 12%, EBV infection in 23%, HPV/EBV coinfection in 12%, and an absence of HPV and EBV infection in 53%. The promoter methylation of the DAPK gene is an important event during carcinogenesis and may have potential clinical application as a marker for the progression and prognosis of cancer. PMID- 17868342 TI - Small cell neuroendocrine carcinoma of the endometrium and laparoscopic staging: a clinicopathologic study of a case and a brief review of the literature. AB - Small cell neuroendocrine (NE) carcinoma is one of the most aggressive tumors that arise in the female genital tract. Small cell carcinoma of the endometrium (SCCE) is an extremely rare disease. Because of its rarity, the only clinical reports are limited to case studies, and therefore, clinical behavior and optimal treatment modalities are not well defined. To the best of our knowledge, we present the first case of SCCE staged by laparoscopic approach. A 54-year-old parous woman admitted with intermittent vaginal spotting. On physical examination, she had a 4- x 3-cm mass fungating out of the cervical os. Magnetic resonance imaging showed an endometrial mass of 25 x 30 x 50 mm in dimensions, invading less than 50% of the depth of the myometrium at the uterine fundus. Pathologic examination revealed undifferentiated malign NE tumor of endometrium of small cell type. The patient underwent laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and laparoscopic pelvic and para-aortic lymphadenectomy. The disease was surgically staged as IB. Histologically, tumor cells were monotone, with scanty, ill-defined cytoplasm and hyperchromatic nuclei. Immunohistochemically, tumor showed positive immunoreactivity for P16, neuron specific enolase, and synaptophysin. She underwent pelvic external radiation and brachytherapy postoperatively. Patient has no evidence of disease after 26 months of follow-up. Small cell NE carcinoma of the endometrium is an extremely rare and aggressive disease. With the availability of skilled endoscopic surgeons, laparoscopic management of women, even with SCCE in early stage, can be a feasible option. PMID- 17868343 TI - Pathology of stage I versus stage III ovarian carcinoma with implications for pathogenesis and screening. AB - The progression of ovarian carcinoma from stage I when it is confined to the ovaries and curable to disseminated abdominal disease, which is usually fatal, is poorly understood. An accurate understanding of this process is fundamental to designing, testing, and implementing an effective screening program for ovarian cancer. Pathologic features of the primary ovarian tumors in 41 FIGO stage I ovarian carcinomas were compared with those in 40 stage III carcinomas. The primary ovarian tumors in stage I cases, when compared with stage III, respectively, were significantly larger (15.4 versus 9.8 cm), were less frequently bilateral (12% versus 75%), more frequently contained a noninvasive component (88% versus 30%), had a higher proportion of a noninvasive component (42% versus 8%), and were more often nonserous (83% versus 20%) (P < 0.001 for all five comparisons). There are significant pathologic differences between the primary ovarian tumors in stage I and III ovarian carcinomas that are very difficult to explain by a simple temporal progression. These findings along with the growing body of literature suggest that early- and advanced-stage ovarian cancers are in many instances biologically different entities. This knowledge may have significant implications for our understanding of the biology of early- and advanced-stage ovarian cancer and therefore on the development of screening strategies for ovarian cancer. PMID- 17868344 TI - Expression of CD133-1 and CD133-2 in ovarian cancer. AB - Cancer stem cells have been isolated from several solid tumors including prostate, colon, liver, breast, and ovarian cancer. Stem cells isolated from nervous system and prostate express CD133 antigen, which is widely used to isolate hematopoietic stem and progenitor cells. The aims of this study were to investigate the expression of the CD133-1 and CD133-2 epitopes in primary ovarian tumors and to biologically characterize CD133(+) ovarian cancer cells, also according to clinicopathologic parameters. Tissue specimens were obtained at primary surgery from 41 ovarian carcinomas; eight normal ovaries and five benign ovarian tumors were also collected. Flow cytometry with monoclonal antibodies against CD133-1 and CD133-2 epitopes was employed. FACS (fluorescence activated cell sorting) analysis enabled the selection of CD133(+) cells, whose epithelial origin was confirmed by immunofluorescence analysis with monoclonal anti cytokeratin 7. CD133(+) cells gave rise to a 4.7 +/- 0.9-fold larger number of colonies than that documented in CD133(-) population (P < 0.001). Moreover, CD133(+) cells showed an enhanced proliferative potential compared to CD133(-) cells. The percentages of CD133-1- and CD133-2-expressing cells were significantly lower in normal ovaries/benign tumors with respect to those in ovarian carcinoma. Both the percentages of CD133-1- and CD133-2-expressing cells were significantly lower in omental metastases than in primary ovarian cancer (P = 0.009 and 0.007 for CD133-1- and CD133-2-expressing cells, respectively). There seems not to be any difference in the distribution of the percentage of CD133-1- and CD133-2-expressing cells according to clinicopathologic parameters and response to primary chemotherapy. CD133-1 and CD133-2 may be useful in order to select and enrich the population of CD133(+) ovarian tumor cells, which are characterized by a higher clonogenic efficiency and proliferative potential. PMID- 17868345 TI - Burden of asthma in the hospital setting: an Australian analysis. AB - OBJECTIVES: This study was designed to report factors associated with asthma hospital admission, such as patient characteristics, type of admission and subsequent outcome i.e. discharge or death, for the years 2000-2005. These data are used for health economic models regarding asthma burden in the hospital setting in Australia. METHODS: Data was obtained from the Australian Centre for Asthma Monitoring using their amalgamated dataset from all states and territories. Admissions under ICD-10 codes J45 'Asthma' plus all subcodes, and J46 'acute severe asthma' were included. Codes for associated comorbidity at the time of admission were identified, as well as the month of death, age, gender and length and the type of stay. Confidence intervals for death rate assumed a binomial distribution because of the rarity of event. RESULTS: The total number of all-cause deaths for the 5-year observation period was 289 from 202,739 asthma separations or 0.14% or 143 deaths/100,000 separations and the highest rate was seen in patients over 45 years. Acute upper respiratory tract infections were reported in up to 25% of all asthma hospital admissions. Length of stay was up to a mean average of 10.2 days in patients who died (SD 15.3). In 5 years observation there was 152,758 emergency asthma admissions which contributed greatly to Australian healthcare burden. CONCLUSIONS: The study demonstrates that emergency admissions dominate asthma care in the hospital setting in Australia, which suggests poor asthma control in some patients with subsequent economic burden. Asthma-related mortality remains a risk for specific patients in the hospital setting. PMID- 17868346 TI - Chikungunya disease with nephritic presentation. PMID- 17868347 TI - Breast carcinoma masquerading as recurrent primary breast lymphoma. PMID- 17868348 TI - Gastric stasis occurs in spontaneous, visually induced, and interictal migraine. AB - OBJECTIVE: To evaluate and compare gastric motility and emptying during spontaneous migraine to previous observations from induced migraine. BACKGROUND: We have previously demonstrated a delay in gastric emptying both during the interictal period and during an induced migraine. A limitation noted in these studies was whether there are differences gastrointestinally during a visually induced migraine compared to spontaneous migraines. To address this, 9 additional studies have been performed to ascertain if there is a similar delay during spontaneous migraine METHODS: Gastric scintigraphy using a standard meal was performed in 3 subjects during 3 periods: spontaneous migraine, induced migraine, and interictal period. RESULTS: On average, the time to half emptying was delayed during spontaneous migraine (124 minutes), during induced migraine (182 minutes), and during the interictal period migraine (243 minutes) compared to normative values established at our center (112 minutes). On average, similar gastric slowing was seen in all 3 groups when the percentage of nuclear material remaining in the stomach at 2 hours was measured. CONCLUSIONS: This study provides additional evidence of gastric stasis in migraineurs interictally during induced and spontaneous migraine. PMID- 17868349 TI - Migraine and topiramate induced dyspnea. AB - Topiramate is effective in migraine headache prophylaxis. Pulmonary symptoms are rarely described as adverse effects. We report the case of a 42-year-old woman with migraine headaches who developed chronic shortness of breath while taking topiramate. Our patient experienced hand paresthesiae at a dose of 25 mg daily, and exercise induced dyspnea at doses above 50 mg daily; these symptoms worsened with increasing topiramate doses. Physical exam and chest x-ray were normal. Blood gas revealed a metabolic acidosis. Symptoms resolved after discontinuation of topiramate. Topiramate induces a lowering of blood carbon dioxide, which is usually asymptomatic. This is due to inhibition of carbonic anhydrase at the proximal renal tubule resulting in impaired proximal bicarbonate reabsorption. The decrease in CO(2) blood level facilitates the occurrence of metabolic acidosis. To our knowledge, this is the first case report of topiramate-induced dyspnea in a patient with migraine headaches. PMID- 17868350 TI - The use of questions to determine the presence of photophobia and phonophobia during migraine. AB - OBJECTIVE: To investigate whether the use of more detailed close-ended questions as part of the routine headache history is helpful when patients initially deny that they are sensitive to light and noise during migraine headaches. BACKGROUND: According to the International Headache Society 2004 criteria, the diagnosis of migraine requires the presence of at least one of the following during a headache: (1) nausea and/or vomiting, (2) photophobia and phonophobia. Evans anecdotally noted that many patients answer the question, "does light or noise bother you during a headache," with a "no" when the answer is really "yes" if they are asked more detailed close-ended questions. METHODS: Consecutive patients fulfilling International Headache Society 2004 criteria for migraine or probable migraine presenting to a headache clinic and a neurology clinic were asked the following questions: "does light bother you during a headache?" If "no," they were then asked, "during a headache, would you prefer to be in bright sunlight or in a dark room?""does noise bother you during a headache?" If "no," they were then asked, "during a headache, would you prefer to be in a room with loud music or in a quiet room?" RESULTS: Eighty-five consecutive patients with migraine or probable migraine were questioned, 71 females (83.5%) and 14 males (16.5%). There was denial of light and sound sensitivity in 24% of patients with routine questioning and then awareness of sensitivity in 93% with the further questioning. A total of 7.1% of the patients were diagnosed with probable migraine. However, if the additional questions were not asked, 8% more of the patients with definite migraine would have been incorrectly diagnosed as probable migraine. CONCLUSION: When patients initially deny light and noise sensitivity during migraine headaches, additional questions should be asked to ensure that their answer is accurate. Not asking the additional questions may result in the over-diagnosis of probable migraine. PMID- 17868352 TI - An expert system for headache diagnosis: the Computerized Headache Assessment tool (CHAT). AB - BACKGROUND: Migraine is a highly prevalent chronic disorder associated with significant morbidity. Chronic daily headache syndromes, while less common, are less likely to be recognized, and impair quality of life to an even greater extent than episodic migraine. A variety of screening and diagnostic tools for migraine have been proposed and studied. Few investigators have developed and evaluated computerized programs to diagnose headache. OBJECTIVES: To develop and determine the accuracy and utility of a computerized headache assessment tool (CHAT). CHAT was designed to identify all of the major primary headache disorders, distinguish daily from episodic types, and recognize medication overuse. METHODS: CHAT was developed using an expert systems approach to headache diagnosis, with initial branch points determined by headache frequency and duration. Appropriate clinical criteria are presented relevant to brief and longer-lasting headaches. CHAT was posted on a web site using Microsoft active server pages and a SQL-server database server. A convenience sample of patients who presented to the adult urgent care department with headache, and patients in a family practice waiting room, were solicited to participate. Those who completed the on-line questionnaire were contacted for a diagnostic interview. RESULTS: One hundred thirty-five patients completed CHAT and 117 completed a diagnostic interview. CHAT correctly identified 35/35 (100%) patients with episodic migraine and 42/49 (85.7%) of patients with transformed migraine. CHAT also correctly identified 11/11 patients with chronic tension-type headache, 2/2 with episodic tension-type headache, and 1/1 with episodic cluster headache. Medication overuse was correctly recognized in 43/52 (82.7%). The most common misdiagnoses by CHAT were seen in patients with transformed migraine or new daily persistent headache. Fifty patients were referred to their primary care physician and 62 to the headache clinic. Of 29 patients referred to the PCP with a confirmed diagnosis of migraine, 25 made a follow-up appointment, the PCP diagnosed migraine in 19, and initiated migraine-specific therapy or prophylaxis in 17. CONCLUSION: The described expert system displays high diagnostic accuracy for migraine and other primary headache disorders, including daily headache syndromes and medication overuse. As part of a disease management program, CHAT led to patients receiving appropriate diagnoses and therapy. Limitations of the system include patient willingness to utilize the program, introducing such a process into the culture of medical care, and the difficult distinction of transformed migraine. PMID- 17868354 TI - Traditional acupuncture in migraine: a controlled, randomized study. AB - OBJECTIVE: To check the effectiveness of a true acupuncture treatment according to traditional Chinese medicine (TCM) in migraine without aura, comparing it to a standard mock acupuncture protocol, an accurate mock acupuncture healing ritual, and untreated controls. BACKGROUND: Migraine prevalence is high and affects a relevant rate of adults in the productive phase of their life. Acupuncture has been increasingly advocated and used in Western countries for migraine treatment, but the evidence of its effectiveness still remains weak. A large variability of treatments is present in published studies and no acupoint selection according to TCM has been investigated so far; therefore, the low level of evidence of acupuncture effectiveness might partly depend on inappropriate treatment. DESIGN AND METHODS: A prospective, randomized, controlled study was performed in 160 patients suffering from migraine without aura, assessed according to the ICD-10 classification. The patients were divided into the following 4 groups: (1) group TA, treated with true acupuncture (according to TCM) plus Rizatriptan; (2) group RMA, treated with ritualized mock acupuncture plus Rizatriptan; (3) group SMA, treated with standard mock acupuncture plus Rizatriptan; (4) group R, without prophylactic treatment with relief therapy only (Rizatriptan). The MIDAS Questionnaire was administered before treatment (T0), at 3 (T1) and 6 months (T2) from the beginning of treatment, and the MIDAS Index (MI) was calculated. Rizatriptan intake was also checked in all groups of patients at T0, T1, and T2. Group TA and RMA were evaluated according to TCM as well; then, the former was submitted to true acupuncture and the latter to mock acupuncture treatment resembling the same as TA. The statistical analysis was conducted with factorial ANOVA and multiple tests with a Bonferroni adjustment. RESULTS: A total of 127 patients completed the study (33 dropouts): 32 belonged to group TA, 30 to group RMA, 31 to group SMA, and 34 to group R. Before treatment the MI (T(0)) was moderate to severe with no significant intergroup differences. All groups underwent a decrease of MI at T(1) and T(2), with a significant group difference at both T(1) and T(2) compared to T(0) (P < .0001). Only TA provided a significant improvement at both T(1) and T(2) compared to R (P < .0001). RMA underwent a transient improvement of MI at T(1). The Rizatriptan intake paralleled the MI in all groups. CONCLUSIONS: TA was the only treatment able to provide a steady outcome improvement in comparison to the use of only Rizatriptan, while RMA showed a transient placebo effect at T1. PMID- 17868355 TI - Retropharyngeal tendinitis: a rare differential diagnosis of severe headaches and neck pain. AB - Retropharyngeal tendinitis is a rare cause of intense neck pain and occipital headache. It is caused by an aseptic inflammatory process in the longus colli tendon, triggered by deposition of calcium hydroxyapatite crystal. Clinically, it can be misdiagnosed as retropharyngeal abscess, traumatic injury, infectious spondylitis, cervical artery dissection, or even meningitis. The diagnosis is made radiographically by a nearly pathognomonic amorphous calcification anterior to C1-C2 and prevertebral soft tissue swelling. We present a new case of this uncommon condition exhibiting some unusual features. PMID- 17868356 TI - Predictors of response to botulinum toxin type A (BoNTA) in chronic daily headache. AB - OBJECTIVE: To evaluate predictors of response to botulinum toxin type A (BoNTA; BOTOX, Allergan Inc., Irvine, CA, USA) in patients with chronic daily headache (CDH). BACKGROUND: Chronic migraine (CM) and chronic tension-type headache (CTTH) form the majority of CDH disorders. Controlled trials indicate that BoNTAis effective in reducing the frequency of headache and number of headache days in patients with CDH disorders. A recent migraine study found that patients with imploding or ocular types of headaches were responders to BoNTA, whereas those with exploding headaches were not. To date, there are no data on factors that might predict response to BoNTA in patients with CDH. METHODS: A total of 71 patients with CM and 11 patients with CTTH were treated with 100 units BoNTA. Every patient received at least 2 sets of injections at intervals of 12-15 weeks; fixed sites, fixed dose, and "follow-the-pain" approaches were used for the injections. A detailed medical history was taken for each patient in addition to recording Migraine Disability Assessment Scale (MIDAS) scores at baseline and every 3 months after each set of injections. Headache frequency was assessed throughout the study from baseline to weeks 24-27. Patients recorded the frequency, severity, and duration of headaches in Headache Diaries. Patients were divided into responders (> or = 50% reduction in both headache frequency and MIDAS scores compared with baseline) and nonresponders (< 50% reduction in either of the above variables). Variables analyzed for predictors of response include headache that is predominantly unilateral or bilateral in location, presence of cutaneous allodynia (scalp allodynia), and presence of pericranial muscle tenderness (also referred to as muscle allodynia). Chi-square analysis was used for parallel-group comparisons (proportion of CM responders vs proportion of CM nonresponders and proportion of CTTH responders vs proportion of CTTH nonresponders). RESULTS: In the CM group, 76.1% (54 /71) of patients were responders to BoNTA, of which 68.5% (37/54) had headache that was predominantly unilateral in location and the remaining 31.5% (17/54) had headache that was predominantly bilateral in location (both P < .01 vs CM nonresponders). Of the 23.9% (17/71) CM nonresponders, 76.5% (13/17) reported predominantly bilateral headache and in the remaining 23.5% (4/17) the headache was unilateral. In the CM responders group, 81.5% (44/54) had clinically detectable scalp allodynia, while pericranial muscle tenderness was present in 61.1% (33/54) (both P < .01 vs CM nonresponders). The presence of scalp allodynia and pericranial muscle tenderness in the CM nonresponders was 11.8% (2/17) and 17.6% (3/17), respectively. In the CTTH group where all patients (100%, 11/11) had bilateral headache, 36.4% (4/11) of patients were responders to BoNTA. All of those CTTH responders (100%, 4/4) had pericranial muscle tenderness (P < .05 vs CTTH nonresponders). None of the CTTH nonresponders had pericranial muscle tenderness. No clinically significant serious adverse events (AEs) were reported. Mild AEs, eg, injection-site pain that persisted for 1-9 days, were reported in 11 patients. One patient had transient brow ptosis. CONCLUSIONS: A greater percentage of patients with CM responded to BoNTA than patients with CTTH. Headaches that were predominantly unilateral in location, presence of scalp allodynia, and pericranial muscle tenderness appear to be predictors of response to BoNTA in CM, whereas in CTTH, pericranial muscle tenderness may be a predictor of response. PMID- 17868357 TI - Thunderclap headache as initial manifestation of Vogt-Koyanagi-Harada disease. AB - A 59-year-old Asian woman suffered from a TCH followed by sudden, binocular blurred vision, mimicking pituitary apoplexy. The diagnostic workup (including fluorescein angiography, MRI of the brain, and CSF analysis) showed severe optic disc swelling and dye leakage of multiple faint hyperfluorescent spots at retinal pigment epithelium level, diffuse pachymeningeal hypertrophy, and monocytic pleocytosis, respectively. VKH disease should be considered in the differential diagnosis of patients presenting with a TCH followed by sudden, bilateral decreased visual acuity. PMID- 17868359 TI - Identification of Tannerella forsythia antigens specifically expressed in patients with periodontal disease. AB - Molecular pathogenesis of Tannerella forsythia, a putative periodontal pathogen, has not yet been adequately elucidated due to limited information on its virulence factors. Here, identification of in vivo expressed antigens of T. forsythia is reported using in vivo-induced antigen technology (IVIAT). Among 13 000 recombinant clones screened, 16 positive clones were identified that reacted reproducibly with sera obtained from patients with periodontal disease. DNA sequences from 12 of these in vivo-induced genes were determined. IVIAT identified protein antigens of T. forsythia include: BspA, a well-defined virulence factor of T. forsythia; enzymes involved in housekeeping functions (tRNA synthetases, glycine hydroxymethyltransferase, and glucoside glucohydrolase); enzymes implicated in tissue destruction (dipeptidyl peptidase IV); a DNA mismatch repair protein; and putative outer membrane proteins of unknown function. The in vivo gene expression of these IVIAT-identified antigens was confirmed by a quantitative real-time PCR analysis. This is, to the best of the authors' knowledge, the first report using IVIAT in T. forsythia. It is anticipated that detailed analysis of the in vivo-induced genes identified by IVIAT in this study will lead to a better understanding of the molecular mechanisms mediating periodontal infection by T. forsythia. PMID- 17868360 TI - Specific mutations in the Mycobacterium tuberculosis rpoB gene are associated with increased dnaE2 expression. AB - In Mycobacterium tuberculosis (MTB), rifampicin resistance is almost invariably due to mutations in the rpoB gene, whose function is critical for cell viability. Most of these mutations, at least initially, impair the fitness of the bacteria but confer a selective advantage when antibiotic pressure is exerted. Subsequent adaptation may be critical to restore fitness. The possibility was considered that MTB with mutations in the rpoB gene elicits a constitutive stress response, increasing the probability of subsequent adaptation. In order to test this hypothesis, the expression of recA and dnaE2, an inducible putative error-prone DNA polymerase, was determined in six different isogenic laboratory-generated rpoB-mutants of MTB. Expression levels were determined with real-time PCR and the data obtained were compared with those of the wild-type parent. In four of the six rpoB mutants, a two- to fivefold induction of dnaE2 was detected (P<0.05). Thus, the presence of specific mutations in rpoB is not only associated with impaired fitness but also results in a detectable, moderate yet persistent increase in the expression of dnaE2 but not recA. PMID- 17868361 TI - Posttranscriptional gene expression regulation in CpG-activated macrophages depends on FXR1P RNA-binding protein. AB - An RNA-binding protein (RBP) was recently identified, FXR1P, which regulates tumour necrosis factor (TNF) gene expression at the posttranscriptional level in response to lipopolysaccharide, was recently identified resulting in higher TNF production in macrophages from FXR1 knockout (KO) mice compared with wild-type (WT) macrophages. In this study, the importance of FXR1P in the induction of TNF by toll-like receptor 7 (TLR7) ligand S28463 and TLR9 ligand CpG is evaluated. The results clearly reveal a much higher level of TNF protein expression in FXR1 KO than in WT macrophages following stimulation with CpG but not with S28463. To better understand the molecular mechanism, both the steady-state levels and the stability of TNF mRNA were assessed. It was found that the TNF mRNA steady-state level was more elevated in CpG-stimulated FXR1-KO macrophages, while the stability of TNF mRNA was not affected in CpG-stimulated FXR1-KO macrophages. It was also established that FXR1P is involved in regulating the expression of several other inflammatory cytokines and chemokines. Together, the data clearly demonstrate the importance of FXR1P RBP in the regulation of a wide spectrum of inflammatory genes and suggest an important role of MAP signalling in the response of macrophages to selected TLR ligands, including CpG. PMID- 17868362 TI - Molecularly assessed shifts of Bifidobacterium ssp. and less diverse microbial communities are characteristic of 5-year-old allergic children. AB - The composition of intestinal microbiota and the Bifidobacterium group community in 20 allergic and 20 nonallergic 5-year-old children was visualized by PCR denaturing gradient gel electrophoresis (DGGE). The number of dominant bands in the DGGE profiles was smaller in allergic children than in nonallergic children (P<0.001). Allergic children mainly formed a single group upon cluster analysis, whereas nonallergic children were divided between four different groups. In allergic children the Bifidobacterium adolescentis species prevailed, and in nonallergic children the Bifidobacterium catenulatum/pseudocatenulatum prevailed (P=0.01 and P=0.01, respectively). The less diverse composition of intestinal microbiota and prevalence of particular species of Bifidobacterium were characteristic of allergic children even at the age of 5 years. PMID- 17868363 TI - Microbial diversity-productivity relationships in aquatic ecosystems. AB - Thanks to recent advances in molecular biology, one's knowledge of microbial co occurrence patterns, microbial biogeography and microbial biodiversity is expanding rapidly. This MiniReview explores microbial diversity-productivity relationships in the light of what is known from the general ecology literature. Analyses of microbial diversity-productivity relationships from 70 natural, experimental, and engineered aquatic ecosystems reveal patterns that are strikingly similar to those that have long been documented for communities of macroorganisms. Microbial ecology and the general science of ecology are thus continuing to converge. PMID- 17868364 TI - Nitrite-oxidizing bacteria guild ecology associated with nitrification failure in a continuous-flow reactor. AB - Nitrification is an important process for nitrogen removal in many wastewater treatment plants, which requires the mutualistic oxidation of ammonia to nitrate by ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB). However, this process can be quite unpredictable because both guilds are conditionally sensitive to small changes in operating conditions. Here, dynamics are examined within the NOB guild in two parallel chemostats operated at low and high dilution rates (0.10 and 0.83 day(-1), respectively) during periods of varying nitrification performance. NOB and AOB guild abundances and nitrogen oxidation efficiency were relatively constant over time in the 0.10 day(-1) reactor; however, the 0.83 day(-1) reactor had two major disturbance episodes that caused destabilization of the NOB guild, which ultimately led to nitrification failure. The first episode caused the extinction of Nitrospira spp. from the system, resulting in chronic incomplete ammonia oxidation and nitrite accumulation. The second episode caused complete loss of nitrification activity, likely resulting from metal toxicity and the previous extinction of Nitrospira spp. from the system. These results exemplify the types of changes that can occur within the NOB guild that result in process impairment or failure, and provide one possible explanation for why nitrification is often unstable at higher dilution rates. PMID- 17868365 TI - Vacuolization correlates with spin-spin relaxation time in motor brainstem nuclei and behavioural tests in the transgenic G93A-SOD1 mouse model of ALS. AB - In recent years, magnetic resonance imaging (MRI) has emerged as a preferred tool for the diagnosis of amyotrophic lateral sclerosis (ALS) in humans. A widely used animal model for human ALS is the G93A-superoxide dismutase 1 (G93A-SOD1) transgenic mouse model. However, the mechanisms for the selective degeneration of motor neurons in the brainstem and spinal cord are still uncertain. In our study, we applied MRI at 4.7 Tesla to non-invasively evaluate pathological alterations in the brainstem of this animal model and to follow the progression of the disease. Extending previous investigation, we used the relaxation parameter T(2) as a suitable measure for the progression of ALS, and evaluated the potential agreement with histological evaluation and behavioural data of open-field tests. In the brainstem of G93A-SOD1 mice, T(2) values were significantly increased in the motor nuclei Nc. V, Nc. VII and Nc. XII, as early as Day 80, i.e. before the average disease onset at about Day 90. Moreover, this increase is associated with a progressive development of vacuoles in the brainstem motor nuclei and a significantly decreased performance in behavioural tests. Overall, MRI is a very sensitive tool to obtain correlates for neuronal degeneration in vivo. Furthermore, MRI enables us to investigate a follow up at different time points of the disease. These advantages are especially useful for therapeutic studies with respect to survival rates of motor neurons using mouse models. Finally, our data suggest that MRI does not only resemble the findings of behavioural tests, but is potentially superior to behavioural studies. PMID- 17868366 TI - Coding of spatial information by soma and dendrite of pyramidal cells in the hippocampal CA1 of behaving rats. AB - The soma and dendrite of a single neuron differ markedly in their anatomical and chemical organization. However, the difference between the neuronal codes by the soma and dendrite in the brain of behaving animals remains unknown. Here, we show that in the hippocampal CA1 of behaving rats, the soma and dendrite of pyramidal cells code distinct spatial information. To detect these neuronal codes, we used a unique extracellular multiunit recording technique with special electrodes (dodecatrodes) and a novel spike-sorting system with an independent component analysis (ICSort). First, we examined whether ICSort could separate extracellular signals from the soma and those from the dendrite of a single cell, in comparison with the separation obtained by a conventional spike-sorting technique. The results suggest that ICSort could distinguish extracellular signals originating from the soma and dendrite. Second, we examined spatial information coded by signals from the soma and dendrite of hippocampal pyramidal cells when the rats were moving in a familiar open environment. The results indicate that the somatic units had single place fields, and showed higher spatial specificity, lower sparsity and lower firing rates than the dendritic units. Therefore, we conclude that a hippocampal pyramidal cell has the ability to transform redundant spatial information received from upstream neurons via the dendrite into more place specific information along the dendrosomatic axis and transmit this information to downstream neurons via the soma. PMID- 17868367 TI - Spatio-temporal dynamics of oscillatory network activity in the neonatal mouse cerebral cortex. AB - We used a 60-channel microelectrode array to study in thick (600-1000 microm) somatosensory cortical slices from postnatal day (P)0-P3 mice the spatio-temporal properties of early network oscillations. We recorded local non-propagating as well as large-scale propagating spontaneous oscillatory activity. Both types of activity patterns could never be observed in neocortical slices of conventional thickness (400 microm). Local non-propagating spontaneous oscillations with an average peak frequency of 15.6 Hz, duration of 1.7 s and maximal amplitude of 66.8 microV were highly synchronized in a network of approximately 200 microm in diameter. Spontaneous oscillations of lower frequency (10.4 Hz), longer duration (23.8 s) and larger amplitude (142.9 microV) propagated with 0.11 mm/s in the horizontal direction over at least 1 mm. These propagating oscillations were also synchronized in a columnar manner, but these waves synchronized the activity in a larger neuronal network of 300-400 microm in diameter. Both types of spontaneous network activity could be blocked by the gap junction antagonist carbenoxolone. Electrical stimulation of the subplate (SP) or bath application of the cholinergic agonist carbachol also elicited propagating network oscillations, emphasizing the role of the SP and the cholinergic system in the generation of early cortical network oscillations. Our data demonstrate that a sufficiently large network in thick neocortical slice preparations is capable of generating spontaneous and evoked network oscillations, which are highly synchronized via gap junctions in 200-400-microm-wide columns. These via synchronized oscillations coupled networks may represent a self-organized functional template for the activity-dependent formation of neocortical modules during the earliest stages of development. PMID- 17868368 TI - Long-term depression of cortico-striatal synaptic transmission by DHPG depends on endocannabinoid release and nitric oxide synthesis. AB - In models of early stage Parkinson's disease (PD), motor deficits are accompanied by excessive activation of striatal glutamate receptors. Metabotropic glutamate group I receptors (mGluR I) play an important but not well-understood role in PD progression. In mouse brain slices, bath application of the mGluR I agonist (RS) DHPG (3,5-dihydroxyphenylglycine, 100 microm for 20 min) caused a long-term depression of corticostriatal transmission (LTD(DHPG)), which was reversed by three mGluR I antagonists: LY 367385, CPCCOEt and MPEP. LTD(DHPG) required nitric oxide (NO) synthesis as it was blocked by the broad-spectrum NO synthase (NOS) inhibitor Nomega-nitro-l-arginine (NL-Arg) and impaired under blockade of neuronal NOS and in endothelial NOS-deficient mice. Release of endocannabinoids (eCB) was critically involved in this form of striatal plasticity givem that the CB1 receptor antagonist AM251 prevented LTD(DHPG), while the CB1 agonist ACEA elicited LTD. The NO synthesis necessary for LTD(DHPG) induction occurred downstream of CB1 activation as ACEA-evoked LTD was also abolished by NL-Arg. These findings are relevant for the pathophysiology of PD, as they link the overactivation of group I mGluRs and striatal NO production. PMID- 17868369 TI - Schwann cells revert to non-myelinating phenotypes in the deafened rat cochlea. AB - Loss of sensory hair cells within the cochlea results in a permanent sensorineural hearing loss and initiates the gradual degeneration of spiral ganglion neurons (SGNs) - the primary afferent neurons of the cochlea. While these neurons are normally myelinated via Schwann cells, loss of myelin occurs as a precursor to neural degeneration. However, the relationship between demyelination and the status of Schwann cells in deafness is not well understood. We used a marker of peripheral myelin (myelin protein zero; P0) and a marker of Schwann cells (S100) to determine the temporal sequence of myelin and Schwann cell loss as a function of duration of deafness. Rat pups were systemically deafened for periods ranging from 2 weeks to greater than 6 months by co administration of frusemide and gentamicin. Cochleae were cryosectioned and quantitative immunohistochemistry used to determine the extent of P0 and S100 labelling within the peripheral processes, SGN soma and their central processes within the modiolus. SGN density was also determined for each cochlear turn. P0 labelling decreased throughout the cochlea with increasing duration of deafness. The reduction in P0 labelling occurred at a faster rate than the SGN loss. In contrast, S100 labelling was not significantly reduced compared with age-matched controls in any cochlear region until 6 months post-deafening. These results suggest that Schwann cells may revert to non-myelinating phenotypes in response to deafness and exhibit greater survival traits than SGNs. The potential clinical significance of these findings for cochlear implants is discussed. PMID- 17868370 TI - Substance P excites globus pallidus neurons in vivo. AB - Substance P is a member of the neurokinin family. Previous studies have reported the existence of substance P and its high-affinity receptor, neurokinin-1 receptor, in globus pallidus. Employing in vivo extracellular recording combined with behavioural tests, the effects of substance P in globus pallidus of rats were studied. Micropressure ejection of the selective neurokinin-1 receptor agonist [Sar9,Met(O2)11] substance P increased the spontaneous firing rate of pallidal neurons in a concentration-dependent manner, with increases of 27.3% at 0.01, 33.4% at 0.03, 45.5% at 0.1, 38.4% at 0.3 and 36.4% at 1.0 mm. The selective neurokinin-1 receptor antagonist SR140333B prevented the excitatory effects induced by [Sar9,Met(O2)11] substance P. In behaving rats, we observed the postural effects of neurokinin-1 receptor activation in the globus pallidus. Consistent with electrophysiological results, unilateral microinjection of [Sar9,Met(O2)11] substance P (0.1 mm) led to a SR140333B-sensitive contralateral deflection in the presence of systemic haloperidol administration. Combining electrophysiological and behavioural findings, we concluded that substance P produces excitatory effects on globus pallidus neurons via neurokinin-1 receptors. PMID- 17868371 TI - Evidence for RPE65-independent vision in the cone-dominated zebrafish retina. AB - An enzyme-based cyclic pathway for trans to cis isomerization of the chromophore of visual pigments (11-cis-retinal) is intrinsic to vertebrate cone and rod vision. This process, called the visual cycle, is mostly characterized in rod dominated retinas and essentially depends on RPE65, an all-trans to 11-cis retinoid isomerase. Here we analysed the role of RPE65 in zebrafish, a species with a cone-dominated retina. We cloned zebrafish RPE65 and showed that its expression coincided with photoreceptor development. Targeted gene knockdown of RPE65 resulted in morphologically altered rod outer segments and overall reduced 11-cis-retinal levels. Cone vision of RPE65-deficient larvae remained functional as demonstrated by behavioural tests and by metabolite profiling for retinoids. Furthermore, all-trans retinylamine, a potent inhibitor of the rod visual cycle, reduced 11-cis-retinal levels of control larvae to a similar extent but showed no additive effects in RPE65-deficient larvae. Thus, our study of zebrafish provides in vivo evidence for the existence of an RPE65-independent pathway for the regeneration of 11-cis-retinal for cone vision. PMID- 17868372 TI - Norepinephrine depletion facilitates recovery of function after focal ischemia in the rat. AB - Previous studies have suggested that increased norepinephrine plays an important role in recovery of function after brain injury; however, the majority of these studies used drugs that are known to also affect other monoamines to increase or decrease norepinephrine. The purpose of the present study was to determine if norepinephrine is required to promote recovery after ischemia. A form of enriched rehabilitation was used to rehabilitate animals after ischemia and the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine was used to selectively destroy norepinephrine projections from the locus coeruleus. Three sensorimotor tests were used to evaluate the recovery of the animals. Depletion of norepinephrine improved sensorimotor recovery in standard-housed animals and did not impede recovery in the rehabilitation groups. Dopamine beta hydroxylase staining was used to confirm N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine-depleted terminal norepinephrine levels. The amount of norepinephrine terminal staining negatively correlated with recovery of function in the staircase test after ischemia. In addition, enriched rehabilitation increased, but depletion of norepinephrine had no effect on, brain-derived neurotrophic factor protein levels, which have also been linked to improved recovery of function. Together the above findings question the previously postulated role of norepinephrine in recovery of function after stroke. PMID- 17868373 TI - Interleukin-1 inhibits firing of serotonergic neurons in the dorsal raphe nucleus and enhances GABAergic inhibitory post-synaptic potentials. AB - In vitro electrophysiological data suggest that interleukin-1 may promote non rapid eye movement sleep by inhibiting spontaneous firing of wake-active serotonergic neurons in the dorsal raphe nucleus (DRN). Interleukin-1 enhances GABA inhibitory effects. DRN neurons are under an inhibitory GABAergic control. This study aimed to test the hypothesis that interleukin-1 inhibits DRN serotonergic neurons by potentiating GABAergic inhibitory effects. In vitro intracellular recordings were performed to assess the responses of physiologically and pharmacologically identified DRN serotonergic neurons to rat recombinant interleukin-1beta. Coronal slices containing DRN were obtained from male Sprague-Dawley rats. The impact of interleukin-1 on firing rate and on evoked post-synaptic potentials was determined. Evoked post-synaptic potentials were induced by stimulation with a bipolar electrode placed on the surface of the slice ventrolateral to DRN. Addition of interleukin-1 (25 ng/mL) to the bath perfusate significantly decreased firing rates of DRN serotonergic neurons from 1.3 +/- 0.2 Hz (before administration) to 0.7 +/- 0.2 Hz. Electrical stimulation induced depolarizing evoked post-synaptic potentials in DRN serotonergic neurons. The application of glutamatergic and GABAergic antagonists unmasked two different post-synaptic potential components: a GABAergic evoked inhibitory post-synaptic potentials and a glutamatergic evoked excitatory post-synaptic potentials, respectively. Interleukin-1 increased GABAergic evoked inhibitory post-synaptic potentials amplitudes by 30.3 +/- 3.8% (n = 6) without affecting glutamatergic evoked excitatory post-synaptic potentials. These results support the hypothesis that interleukin-1 inhibitory effects on DRN serotonergic neurons are mediated by an interleukin-1-induced potentiation of evoked GABAergic inhibitory responses. PMID- 17868374 TI - Functional specificity of human premotor-motor cortical interactions during action selection. AB - Functional connections between dorsal premotor cortex (PMd) and primary motor cortex (M1) have been revealed by paired-pulse transcranial magnetic stimulation (TMS). We tested if such connections would be modulated during a cognitive process (response selection) known to rely on those circuits. PMd-M1 TMS applied 75 ms after a cue to select a manual response facilitated motor-evoked potentials (MEPs). MEPs were facilitated at 50 ms in a control task of response execution, suggesting that PMd-M1 interactions at 75 ms are functionally specific to the process of response selection. At 100 ms, PMd-M1 TMS delayed choice reaction time (RT). Importantly, the MEP (at 75 ms) and the RT (at 100 ms) effects were correlated in a way that was hand-specific. When the response was made with the M1-contralateral hand, MEPs correlated with slower RTs. When the response was made with the M1-ipsilateral hand, MEPs correlated with faster RTs. Paired-pulse TMS confined to M1 did not produce these effects, confirming the causal influence of PMd inputs. This study shows that a response selection signal evolves in PMd early during the reaction period (75-100 ms), impacts on M1 and affects behaviour. Such interactions are temporally, anatomically and functionally specific, and have a causal role in choosing which movement to make. PMID- 17868375 TI - Dopamine release is heterogeneous within microenvironments of the rat nucleus accumbens. AB - Many individual neurons within the intact brain fire in stochastic patterns that arise from interactions with the neuronal circuits that they comprise. However, the chemical communication that is evoked by these firing patterns has not been characterized because sensors suitable to monitor subsecond chemical events in micron dimensions have only recently become available. Here we employ a voltammetric sensor technology coupled with principal component regression to examine the dynamics of dopamine concentrations in the nucleus accumbens (NAc) of awake and unrestrained rats. The sensor has submillimeter dimensions and provides high temporal (0.1 s) resolution. At select locations spontaneous dopamine transient concentration changes were detected, achieving instantaneous concentrations of approximately 50 nm. At other locations, transients were absent even though dopamine was available for release as shown by extracellular dopamine increases following electrical activation of dopaminergic neurons. At sites where dopamine concentration transients occur, uptake inhibition by cocaine enhances the frequency and magnitude of the rapid transients while also causing a more gradual increase in extracellular dopamine. These effects were largely absent from sites that did not support ongoing transient activity. These findings reveal an unanticipated spatial and temporal heterogeneity of dopamine transmission within the NAc that may depend upon the firing of specific subpopulations of dopamine neurons. PMID- 17868376 TI - A comprehensive and critical review of dental implant prognosis in periodontally compromised partially edentulous patients. AB - OBJECTIVES: The outcome of implant treatment in periodontally compromised partially edentulous patients has not been completely clarified. Therefore, the aim of the present study was to perform, applying a systematic methodology, a comprehensive and critical review of the prospective studies published in English up to and including August 2006, regarding the short-term (<5 years) and long term (>or=5 years) prognosis of osseointegrated implants placed in periodontally compromised partially edentulous patients. MATERIAL AND METHODS: Using The National Library Of Medicine and Cochrane Oral Health Group databases, a literature search for articles published up to and including August 2006 was performed. At the first phase of selection the titles and abstracts and at the second phase full papers were screened independently and in duplicate by the three reviewers (I. K. K., S. K., I. F.). RESULTS: The search provided 2987 potentially relevant titles and abstracts. At the first phase of evaluation, 2956 publications were rejected based on title and abstract. At the second phase, the full text of the remaining 31 publications was retrieved for more detailed evaluation. Finally, 15 prospective studies were selected, including seven short term and eight long-term studies. Because of considerable discrepancies among these studies, meta-analysis was not performed. CONCLUSIONS: No statistically significant differences in both short-term and long-term implant survival exist between patients with a history of chronic periodontitis and periodontally healthy individuals. Patients with a history of chronic periodontitis may exhibit significantly greater long-term probing pocket depth, peri-implant marginal bone loss and incidence of peri-implantitis compared with periodontally healthy subjects. Even though the short-term implant prognosis for patients treated for aggressive periodontitis is acceptable, on a long-term basis the matter is open to question. Alterations in clinical parameters around implants and teeth in aggressive periodontitis patients may not follow the same pattern, in contrast to what has been reported for chronic periodontitis patients. However, as only three studies comprising patients treated for aggressive periodontitis were selected, more studies, specially designed, are required to evaluate implant prognosis in this subtype of periodontitis. As the selected publications exhibited considerable discrepancies, more studies, uniformly designed, preferably longitudinal, prospective and controlled, would be important. PMID- 17868377 TI - A novel characteristic of porous titanium oxide implants. AB - OBJECTIVE: The anatase form of titanium dioxide (TiO2) is one of the most common crystalline forms of TiO2 and is normally produced by oxidation of titanium via thermal oxidation or anodizing. This crystalline form exhibits photocatalytic activity when it is irradiated with ultraviolet A (UVA) light. The aim of the current study was to analyze the crystal structure of anodic-oxidized TiUnite implants and to confirm the photocatalytic properties in vitro and in vivo. MATERIAL AND METHODS: Cross-sectional observations by transmission electron microscopy were used to determine the surface crystal structure on the TiUnite implant. Subsequently, photocatalytic activity was confirmed by degradation of methylene blue, and hydrophilicity was measured based on the water contact angle. Furthermore, the in vivo effects of the photocatalytic activity of this compound were investigated. RESULTS: An amorphous layer that was about 10 microm thick was observed on the TiUnite implant surface. In the amorphous layer, the anatase form of the crystalline TiO2 was identified. Photocatalytic activity was clearly demonstrated by the bleaching effect of methylene blue under UVA illumination. The contact angle decreased from 44 degrees to 11 degrees after UVA illumination. Although these data suggest increased hydrophilicity for the TiUnite implant, the bone-to-metal contact at 4 weeks was not influenced. CONCLUSION: The anodic oxidized TiUnite implant has inherent photocatalytic activity. UVA illumination increases the surface hydrophilicity of the implant. However, this increase in hydrophilicity does not improve bone apposition to the implant surface at 4 weeks. PMID- 17868378 TI - Cell cycle-dependent transcription of cyclin B2 is influenced by DNA methylation but is independent of methylation in the CDE and CHR elements. AB - DNA methylation is an important mechanism involved in embryogenesis and tumor development. Changing cytosines to 5-methylcytosines in CpG dinucleotides has been found to be responsible for the inactivation of tumor suppressor genes by repressing transcription. A central cell cycle regulator whose synthesis is controlled by transcription is cyclin B. In mammalian cells, cyclin B1 and B2 proteins are well characterized and often found to be overexpressed in cancer patients. Transcription from cyclin B1 and B2 promoters during the cell cycle is dependent upon a combination of two sites named 'cell cycle-dependent element' (CDE) and 'cell cycle genes homology region' (CHR), through repression in G(0) and G(1) followed by release in G(2)/M. Here we show that the cyclin B2 promoter contains a CpG island and that 5-aza-deoxycytidine treatment leads to deregulation of cell cycle-dependent mRNA expression from this gene via a loss of repression in G(0). Furthermore, deletion of the DNA methyltransferase genes DNMT1 and DNMT3b leads to an increase in transcription of cyclin B2. Additionally, DNA methylation in vitro prevents transcriptional activation of the cyclin B2 promoter in G(2)/M. Analysis in vivo of the cyclin B2 core promoter revealed that the CDE/CHR site is partially methylated. However, quantitative in vivo analysis of the CpG-methylation level of the CDE during cell division indicates that CpG methylation is independent of the cell cycle. We conclude that DNA methylation affects cell cycle-dependent transcription of cyclin B2 but that regulation through CDE/CHR is independent of cytosine methylation. PMID- 17868379 TI - Pyruvate reduces DNA damage during hypoxia and after reoxygenation in hepatocellular carcinoma cells. AB - Pyruvate is located at a crucial crossroad of cellular metabolism between the aerobic and anaerobic pathways. Modulation of the fate of pyruvate, in one direction or another, can be important for adaptative response to hypoxia followed by reoxygenation. This could alter functioning of the antioxidant system and have protective effects against DNA damage induced by such stress. Transient hypoxia and alterations of pyruvate metabolism are observed in tumors. This could be advantageous for cancer cells in such stressful conditions. However, the effect of pyruvate in tumor cells is poorly documented during hypoxia/reoxygenation. In this study, we showed that cells had a greater need for pyruvate during hypoxia. Pyruvate decreased the number of DNA breaks, and might favor DNA repair. We demonstrated that pyruvate was a precursor for the biosynthesis of glutathione through oxidative metabolism in HepG2 cells. Therefore, glutathione decreased during hypoxia, but was restored after reoxygenation. Pyruvate had beneficial effects on glutathione depletion and DNA breaks induced after reoxygenation. Our results provide more evidence that the alpha-keto acid promotes the adaptive response to hypoxia followed by reoxygenation. Pyruvate might thus help to protect cancer cells under such stressful conditions, which might be harmful for patients with tumors. PMID- 17868380 TI - Characterization of a methyl jasmonate and wounding-responsive cytochrome P450 of Arabidopsis thaliana catalyzing dicarboxylic fatty acid formation in vitro. AB - A fatty-acid-metabolizing enzyme from Arabidopsis thaliana, CYP94C1, belonging to the cytochrome P450 family was cloned and characterized. CYP94C1 was heterologously expressed in a Saccharomyces cerevisiae strain (WAT11) engineered for P450 expression. When recombinant yeast microsomes were incubated with lauric acid (C12:0) for 15 min, one major metabolite was formed. The product was purified and identified by GC/MS as 12-hydroxylauric acid. Longer incubation (40 min) led to the formation of an additional metabolite identified by GC/MS as dodecadioic acid. This diacid was also produced by incubation with 12 hydroxylauric acid. These compounds were not produced by incubating microsomes from yeast transformed with a void plasmid, demonstrating the involvement of CYP94C1. This new enzyme also metabolized fatty acids of varying aliphatic chain lengths (C12 to C18) and in-chain modifications, for example, degree of unsaturation or the presence of an epoxide as an additional polar functional group. Transcription of the gene encoding CYP94C1 is enhanced by stress, treatment with the hormone methyl jasmonate and wounding. Treatment with methyl jasmonate also induced lauric acid metabolism in microsomes prepared from Arabidopsis. The induction of hydroxylase activity was dose dependent and increased with exposure time, reaching 16x higher in microsomes from 24-h treated Arabidopsis compared with control plants. Analysis of the metabolites showed a mixture of 12-, 11- and 10-hydroxylauric acids, revealing for the first time the presence of fatty acid in-chain hydroxylase in Arabidopsis. PMID- 17868381 TI - Interactions between the West Nile virus capsid protein and the host cell-encoded phosphatase inhibitor, I2PP2A. AB - The West Nile virus (WNV) capsid protein functions in virus assembly to package genomic RNA into nucleocapsid structures. It is becoming clear, that in addition to their structural roles, capsid proteins of RNA viruses have non-structural functions. For example, the WNV capsid protein has been implicated as a pathogenic determinant. Presumably, many, if not all, of the non-structural functions of this protein involve interactions with host cell-encoded proteins. In the present study, we used affinity purification to isolate human proteins that bind to the WNV capsid protein. One of the capsid binding proteins is I(2)(PP2A), a previously characterized inhibitor of the serine/threonine phosphatase PP2A. Mapping studies revealed that capsid binding site overlaps with the region of I(2)(PP2A) that is required for inhibition of PP2A activity. Moreover, expression of the WNV capsid protein resulted in significantly increased PP2A activity and expected downstream events, such as inhibition of AP1 dependent transcription. Infected cells treated with I(2)(PP2A)-specific siRNAs produced less infectious virus than control siRNA-transfected cells, but this difference was minimal. Together, our data indicate that interactions between WNV capsid and I(2)(PP2A) result in increased PP2A activity. Given the central role of this phosphatase in cellular physiology, capsid/I(2)(PP2A) interactions may yet prove to be important for viral pathogenesis. PMID- 17868382 TI - The major outer sheath protein of Treponema denticola selectively inhibits Rac1 activation in murine neutrophils. AB - Treponema denticola major outer sheath protein (Msp) inhibits neutrophil chemotaxis in vitro, but key regulatory mechanisms have not been identified. Because the Rac small GTPases regulate directional migration in response to chemoattractants, the objective was to analyse the effects of Msp on formyl methionyl-leucyl-phenylalanine (fMLP)-mediated neutrophil polarization and Rac activation in murine neutrophils. Msp pretreatment of neutrophils inhibited both polarization and chemotactic migration in response to fMLP. Activation of small GTPases was measured by p21 binding domain (PBD) pulldown assays, followed by Western analysis, using monoclonal anti-Rac1, anti-Rac2, anti-cdc42 and anti-RhoA antibodies. Enriched native Msp selectively inhibited fMLP-stimulated Rac1 activation in a concentration-dependent manner, but did not affect Rac2, cdc42 or RhoA activation. Murine neutrophils transfected with vectors expressing fluorescent probes PAK-PBD-YFP and PH-AKT-RFP were used to determine the effects of Msp on the localization of activated Rac and PI3 kinase products. Real-time confocal images showed that Msp inhibited the polarized accumulation of activated Rac and PI3-kinase products upon exposure to fMLP. The findings indicate that T. denticola Msp inhibition of neutrophil polarity may be due to the selective suppression of the Rac1 pathway. PMID- 17868383 TI - Plasma aldosterone response to the low-dose adrenocorticotrophin (ACTH 1-24) stimulation test. AB - BACKGROUND: Endocrine tests for adrenal insufficiency use pharmacological doses of stimulant such as ACTH. More physiological tests have often used high-dose protocols for sampling frequency. AIMS: To evaluate the response of plasma aldosterone concentration to low doses (125, 250 and 500 ng/m(2) body surface area) of synthetic ACTH. DESIGN: A randomised trial in six normal adult males aged 18-27 years. MATERIALS AND METHODS: Aldosterone concentration was measured by radioimmunoassay in serum from blood samples taken at 10 min intervals for 90 min. RESULTS: All three doses produced a significant rise in plasma aldosterone concentration (125 ng/m(2), P = 0.003; 250 ng/m(2), P < 0.001; 500 ng/m(2), P < 0.001) but there was no effect of dose on either the peak or incremental plasma aldosterone concentration. Mean time to peak was similar between the doses and the two higher doses were associated with a longer secretory profile (125 ng/m(2) 56 (26 SD) mins, 250 ng/m(2) 74 (19) mins, 500 ng/m(2) 77 (21) mins; F = 3.39; P = 0.04). Peaks of 100% were detected within 30 min of drug administration and peak response was associated with the prestimulation plasma aldosterone concentration (r = 0.45; P = 0.003). The between- and within-individual coefficients of variation for prestimulation concentrations were 37.0% and 32.8%, and for the peak response were 27.2% and 27.2%, respectively. CONCLUSIONS: The response of plasma aldosterone concentrations to low-dose ACTH administration requires a blood sampling protocol of 0, 10, 20 and 30 min to capture concentrations near the peak response. The high-dose protocol would have missed the response. Over the dose range studied no dose-response was observed so the selection of dose should be based on the dose effective to release steroids in the glucocorticoid pathway if this study is to be used in conjunction with such evaluation. PMID- 17868384 TI - Effect of growth hormone deficiency and recombinant hGH (rhGH) replacement on the hypothalamic-pituitary-adrenal axis in children with idiopathic isolated GH deficiency. AB - OBJECTIVE: Recombinant hGH (rhGH) therapy may unmask central hypoadrenalism in adults with organic GH deficiency (GHD), likely by normalizing 11beta hydroxysteroid dehydrogenase type 1 isoenzyme (11betaHSD1) activity and reducing cortisone to cortisol conversion. The aim of the present study was to evaluate the hypothalamic-pituitary-adrenal (HPA) axis in children with idiopathic isolated GHD and normal pituitary magnetic resonance imaging (MRI) both before and during rhGH therapy. DESIGN AND PATIENTS: This was a single-centre study of 10 consecutive children [five males and five females, mean age: 12.2 +/- 1.0 year]. Evaluation was performed at baseline and on rhGH (mean duration: 10.9 +/- 2.9 months, mean dose: 0.030 +/- 0.002 mg/kg bw/day). MEASUREMENTS: HPA function was assessed by serum cortisol levels before and after appropriate provocative stimuli, that is, 1 microg ACTH test (N = 5 patients) or insulin tolerance test (ITT, N = 5 patients), evaluating all children with the same stimulation test both before and during rhGH therapy. Central hypoadrenalism was excluded by the presence of either a peak of > 500 nmol/l or a rise in cortisol levels of > 200 nmol/l, after both tests. RESULTS: On rhGH therapy, serum IGF-I levels normalized, while serum cortisol and ACTH levels did not significantly differ from those recorded at baseline. The mean serum cortisol peak after both provocative tests was not significantly different on rhGH therapy and at baseline (498 +/- 41 vs. 580 +/- 35 nmol/l, respectively, P = 0.06), the mean cortisol rise being 280 +/- 45 and 270 +/- 36 nmol/l on rhGH and at baseline, respectively. CONCLUSIONS: According to the diagnostic criteria, no child became hypoadrenal on rhGH, contrary to what observed in patients with organic GHD, further supporting the view that only in patients with organic multiple pituitary hormone deficiency GHD masks the presence of a hidden central hypoadrenalism. PMID- 17868385 TI - Endoscopic removal of an unusual foreign body in the sphenoid sinus: an oral implant. AB - AIM: Migration of oral implants displaced in the maxillary sinus toward the sphenoid sinus is an extremely rare event. This case report is focused on the possibility of treating such a rare complication by means of endoscopic treatment through the nasal cavity. MATERIAL AND METHODS: A 45-year-old female patient received one oral implant for the substitution of the left first upper molar, but during the surgical procedure the implant was displaced in the maxillary sinus. Owing to a delay in treatment, a spontaneous migration of the implant in the sphenoid sinus occurred. RESULTS: The implant was removed endoscopically through the nasal cavity: postoperative recovery was uneventful. CONCLUSION: To the authors' knowledge, this case represents the first report concerning migration of an oral implant into the sphenoid sinus and demonstrates the reliability and safety of an endoscopically driven surgical removal of the foreign body, thus preventing potential complications with extremely low postoperative morbidity. PMID- 17868386 TI - A retrospective analysis of the failure rate of three different orthodontic skeletal anchorage systems. AB - OBJECTIVES: The aim of this retrospective study was to assess systematically the case distribution among three types of mini-implants and to evaluate the clinical factors that influence the failure rates of mini-implants used as an orthodontic anchorage. MATERIAL AND METHODS: Data for 359 mini-implants (miniplates, miniscrews, and microscrews) in 129 patients were collected. The factors related to mini-implant failure were evaluated using univariate analysis and multivariate stepwise logistic regression analysis. RESULTS: Among these three different types of skeletal anchorage, there was a significant difference between the failure rates of these mini-implants, with the miniscrews and microscrews showing much higher failure rates. There were no significant differences in failure rates among the mini-implants for the following variables: gender, type of malocclusion, local or full-arch treatment, whether on the buccal or lingual side, length of the screw, loading pattern, or the duration of the healing phase. Greater risks for failure were found in younger patients, when an implant was placed for retraction/protraction, when it was placed on the mandibular arch, when it was placed anterior to the second premolars, or when using the miniscrew/microscrew systems. After adjusting for potential confounding effects, only three factors (type of mini-implant, placement on the mandibular arch, and age) were found to be statistically significant in predicting mini-implant failures (P<0.05) with an R2 value of 85.2%. CONCLUSIONS: Mini-implants placed in younger patients or placed on the mandibular arch are at a greater risk of failing. The miniplate system has greater stability compared with miniscrews or microscrews. However, it requires flap surgery for insertion and removal, which usually causes swelling and discomfort. Therefore, selection of the proper type of skeletal anchorage should be based on the specific treatment needs of each individual patient. PMID- 17868387 TI - Oily calcium hydroxide suspension (Osteoinductal) used as an adjunct to guided bone regeneration: an experimental study in rats. AB - OBJECTIVES: To evaluate whether an oily calcium hydroxide suspension (OCHS) promotes bone healing when used as an adjunct to guided bone regeneration (GBR). MATERIAL AND METHODS: Rigid, hemispherical, teflon capsules were placed with their open part facing the lateral surface of the ramus on both sides of the mandible in 10 adult Wistar rats. In each animal, one capsule was filled out with an OCHS (test) before placement, while the capsule on the other side was left empty (control). After 4 months of healing, the animals were sacrificed and histological sections containing the capsules and the neighboring soft and hard tissues were prepared. On three to four sections taken by uniformly random sampling from each specimen, the relative volumes of (1) the newly formed bone (mineralized bone and marrow), (2) the soft connective tissue, (3) the residual OCHS, and (4) the acellular (empty) space inside the capsule were estimated by a point-counting technique, and expressed as percentage of the space originally created by the capsule. RESULTS: There was no new bone formation inside the capsules in all but one test specimen, where only a minimal amount of newly formed bone could be observed in continuation with the lateral surface of the ramus. OCHS had a homogenous appearance and occupied the major portion (79.4%) of the space created by the capsule. No signs of active resorption of the material could be observed. On the contrary, 31.5% of the space provided by the capsule was filled out with newly formed bone in the control group. The new bone had a trabecular appearance with large marrow spaces filled with hematopoietic and fatty marrow. The rest of the capsule space in the controls appeared empty. CONCLUSION: OCHS may hamper bone healing when used as an adjunct to GBR. PMID- 17868388 TI - TBX22 mutations are a frequent cause of non-syndromic cleft palate in the Thai population. AB - Mutations in the TBX22 gene underlie an X-linked malformation syndrome with cleft palate (CP) and ankyloglossia. Its mutations also result in non-syndromic CP in some populations. To investigate whether mutations in TBX22 play a part in the formation of non-syndromic CP in the Thai population, we performed mutation analysis covering all the coding regions of the TBX22 gene in 53 unrelated Thai patients with non-syndromic CP. We identified four potentially pathogenic mutations, 359G-->A (R120Q), 452G-->T (R151L), 1166C-->A (P389Q), and 1252delG in four different patients. All mutations were not detected in at least 112 unaffected ethnic-matched control chromosomes and had never been previously reported. R120Q and R151L, found in two sporadic cases, were located in the DNA binding T-box domain. P389Q and 1252delG, found in two familial cases, were at the carboxy-terminal region, which has never been described. Our study indicates that TBX22 mutations are responsible for a significant proportion of Thai non syndromic CP cases confirming its importance as a frequent cause of non-syndromic CP across different populations. PMID- 17868389 TI - The role of common genetic risk variants in Parkinson disease. AB - Despite the discovery of at least five pathogenic genes in Parkinson disease (PD), the genetic etiology in the vast majority of PD remains to be clarified. Common genetic variants could act as susceptibility risk factors. Our previous meta-analysis of PD genetic association studies, over a 30-year period yielded four genes (N-acetylcysteine 2, monoamine oxidase B, glutathione transferase, and mitochondrial tRNA), as their common variants were found to be associated with PD. More recently, international collaborative studies and meta-analysis have identified the S18Y variant of ubiquitin carboxy-terminal hydrolase L1, Rep 1 variant of alpha-synuclein and tau H1 haplotype to be genetic susceptibility risk/protective factors. However, the most significant, common genetic risk factor in PD has been its association with the leucine-rich repeat kinase-2 (LRRK2) G2385R variant. We conducted an analysis of independent studies involving 2205 PD and 1817 controls and found the average carrier rate of G2385R variant to be about 9% in PD and 4% in controls (p < 0.001; odds ratio: 2.27; 95% confidence interval: 1.78-2.9). A higher frequency of G2385R carriers has been observed in familial PD when compared with sporadic patients. Based on current evidence, certain common genetic variants are likely to modulate the risk of PD. PMID- 17868390 TI - A novel DFNA5 mutation, IVS8+4 A>G, in the splice donor site of intron 8 causes late-onset non-syndromic hearing loss in a Chinese family. AB - We report here the clinical, genetic, and molecular characteristics of a large Chinese family exhibiting non-syndromic, late-onset autosomal dominant sensorineural hearing loss. Clinical evaluation revealed variable phenotypes of hearing loss in terms of severity and age-at-onset of disease in these subjects. Genome-wide linkage analysis mapped the disease gene to the DFNA5 locus with a maximum two-point log odds score of 5.39 at [theta] = 0 for marker D7S2457. DNA sequencing of DFNA5 revealed a novel heterozygous IVS8+4 A>G substitution in the splice donor site of intron 8. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed skipping of exon 8 in the mutant transcript. This mutation faithfully cosegregated with hearing loss in the family. In addition, the mutation was absent in 100 unrelated control DNA samples of Chinese origin. The IVS8+4 A>G mutation is predicted to create a shift in the reading frame and introduce a stop codon at position 372, thereby resulting in a prematurely truncated DFNA5 protein. Up to date, a total of four mutations in DFNA5 have been reported to lead to hearing impairment, all of them result in skipping of exon 8 at the mRNA level. Our findings provide further support for the hypothesis that DFNA5-associated hearing loss is caused by a very specific gain-of-function mutation. PMID- 17868391 TI - Topical kinetin 0.1% lotion for improving the signs and symptoms of rosacea. AB - Many patients with rosacea are unable to tolerate extended treatment periods with topical agents because of the unusually high skin sensitivity that often accompanies rosacea. Kinetin (N(6)-furfuryladenine) is a plant cytokinin that reportedly helps restore skin barrier function and may be useful to ameliorate the signs and symptoms of rosacea. The purpose of this open-label study was to determine the tolerance and efficacy of twice-daily application of kinetin 0.1% lotion for improving the signs and symptoms of mild to moderate facial rosacea. Subjects applied kinetin 0.1% lotion twice daily to the face, with daily use of a sunscreen of sun protection factor 30. Subjects were evaluated at baseline and at 4-week intervals for 12 weeks to assess efficacy and tolerance. Results of this study suggest that kinetin 0.1% lotion is a well-tolerated moisturizing lotion option for subjects with mild to moderate inflammatory rosacea. PMID- 17868392 TI - Phacomatosis pigmentokeratotica associated with a suprasellar dermoid cyst and leg hypertrophy. AB - Phacomatosis pigmentokeratotica (PP) is a mosaic disorder that represents a distinct epidermal naevus syndrome. Its defining features are an epidermal naevus that is usually of the sebaceous type and a speckled lentiginous naevus arranged in a chequerboard pattern. In addition, there are neurological, ophthalmological and skeletal abnormalities, including limb hemiatrophy with muscular weakness, ptosis, seizures and ipsilateral segmental hyperaesthesia and hyperhidrosis. We report a 44-year-old man with an extensive epidermal naevus and an ipsilateral speckled lentiginous naevus. He also had ipsilateral right leg hypertrophy and a suprasellar dermoid cyst with associated neurological abnormalities. We propose that this case represents an unusual example of PP. PMID- 17868393 TI - Globalization of DNA-based prenatal diagnosis for recessive dystrophic epidermolysis bullosa. AB - Globalization of economies and improvements in international telecommunications has led to increased demand for better access to the latest developments in healthcare, wherever they may be available. In this report, we describe the first case from Thailand of DNA-based prenatal testing of a mother at risk for recurrence of severe recessive dystrophic epidermolysis bullosa (RDEB), whose affected child had died in early childhood. In the absence of previous access to prenatal diagnostic tests, the mother had undergone several terminations for fear of having another affected child. To prevent this happening again, DNA from the mother and her consanguineous partner was sent from Bangkok to a specialist laboratory at St John's Institute of Dermatology in London and screened for pathogenic mutations in the COL7A1 gene: both individuals were shown to be heterozygous carriers of a splice-site mutation, c.2440G --> C. In a subsequent pregnancy, amniocentesis was performed at 18 weeks' gestation in Bangkok, and fetal DNA was extracted and sent to London for analysis. Restriction endonuclease digestion of the amplified fetal DNA revealed the wild-type COL7A1 sequence only, and 5 months later, a clinically unaffected boy was born. This case represents the first example of DNA-based prenatal diagnosis for RDEB in Thailand and illustrates the benefits for patients in establishing international links with diagnostic centres with technological expertise that is not widely available in certain countries. PMID- 17868394 TI - Linear IgA bullous dermatosis responsive to trimethoprim-sulfamethoxazole. PMID- 17868395 TI - The effect of the sun on expression of beta-catenin, p16 and cyclin d1 proteins in melanocytic lesions. AB - BACKGROUND: The tumour suppressor gene product, p16, is often inactivated during melanoma malignant progression. Although the importance of p16 in melanomas is well documented, its relationship with cyclin D1, beta-catenin and ultraviolet radiation (UVR) remains unclear. AIM: To determine the role of these cell cycle related proteins and high-risk sun exposure in the biological behaviour of melanocytic lesions. METHODS: We used immunohistochemistry to examine 28 melanocytic naevi (MN; 9 congenital and 19 acquired types) and 24 primary cutaneous malignant melanomas (CMM; 19 nodular melanomas, 3 lentigo maligna melanomas, 1 acral lentiginous melanoma and 1 superficial spreading melanoma) for the presence of p16, cyclin D1 and beta-catenin. The melanocytic lesions were classified into two groups to examine the effects of UVR on these three proteins: high risk of sun exposure (chronically sun damaged; CSD), or low risk of sun exposure (nonchronically sun damaged; non-CSD). We evaluated the relationship between the production of these proteins and the histopathological and clinical characteristics of the lesions. RESULTS: Production of p16 was repressed in most CMM, but not in MN (P < 0.0001). Cyclin D1 was overproduced in CMM but not in MN, and beta-catenin was frequently overproduced both in MN and CMM. Overproduction of beta-catenin was not common in CSD melanocytic lesions, but was more frequent in non-CSD melanocytic lesions (P = 0.027). CONCLUSION: An immunohistochemical panel including melanocytic markers enriched by p16 and cyclin D1 could be used to differentiate some borderline melanocytic lesions. In addition, the Wnt/beta catenin pathway was more frequently activated in non-CSD than in CSD melanocytic lesions. PMID- 17868396 TI - Transient acantholytic dermatosis associated with B symptoms of follicular lymphoma. PMID- 17868397 TI - Acute-onset adult dermatomyositis presenting with erythroderma and diplopia. PMID- 17868398 TI - Reoperation for sella haematoma after pituitary surgery. AB - OBJECTIVE: Although occasionally discussed as a general complication in large pituitary series, the incidence of reoperation for postoperative sella haematoma is unclear. We retrospectively reviewed a large pituitary surgical series to determine the incidence and associated factors of this complication. DESIGN: We reviewed all pituitary surgery at Mayo Rochester from January 1987 until January 2007. There were 2312 transsphenoidal procedures during this period. PATIENTS: All patients had proven pituitary pathology by computed tomography (CT) or magnetic resonance imaging and pituitary function studies. MEASUREMENTS: Reoperation for sella haematoma and perioperative clinical correlations were the only measurement tools. It is indeterminate how many patients had postoperative sella haematoma without visual loss because routine postoperative CT scanning was not performed. RESULTS: Three patients underwent reoperation for postoperative haematoma in the sella by three different endocrine neurosurgeons, and all three patients had progressive postoperative visual loss. All initial operations were for large macroadenomas; two had early postoperative hypertension that may have been a contributor; and one had markedly thickened bone felt to be the source of bleeding and deterioration 24 h later. CONCLUSIONS: Reoperation for postoperative sellar haematoma is uncommon. However, postoperative progressive visual loss was clinically present in all three patients, and labile hypertension postoperatively may play a role. PMID- 17868399 TI - Phaeochromocytoma and mixed corticomedullary tumour - a rare cause of Cushing's syndrome and labile hypertension in a primigravid woman postpartum. PMID- 17868400 TI - Hexokinase III, cyclin A and galectin-3 are overexpressed in malignant follicular thyroid nodules. AB - BACKGROUND: Distinguishing malignant thyroid nodules in patients with follicular cytology by fine-needle aspiration (FNA) remains problematic. The large majority of thyroid nodules (> 85%) are overtreated. Therefore, a clear need exists to develop more accurate initial diagnostic tests for follicular thyroid nodules. Galectin-3 is the most recent promising marker to aid discrimination between benign and malignant thyroid lesions; however, this biomarker can be absent in follicular malignancies. AIMS: This study was undertaken to determine whether additional biomarkers can help to discriminate between benign and malignant thyroid nodules. METHODS: Surgical specimens of 36 patients with benign (n = 12) and malignant (n = 24) thyroid nodules showing follicular cytology were assessed by immunohistochemistry for the expression of galectin-3 and novel biomarkers. RESULTS: Expression of hexokinase III (HK III) (P = 0.000) cyclin A (P = 0.002) and galectin-3 (P = 0.003) differed significantly between benign and malignant thyroid nodules. HK III had a sensitivity of 79% [95% confidence interval (CI) 60 91] and a specificity of 100% (95% CI 76-100) in predicting malignancy. Galectin 3 had a sensitivity of 79% (95% CI 56-91) and a specificity of 75% (95% CI 47-91) in predicting malignancy. Combining HK III, cyclin A and galectin-3 in a parallel test increased the sensitivity to 96% (95% CI 80-99) while the specificity remained at a high level of 75% (95% CI 47-91). Leave-one-out cross-validation demonstrated a stable predictive validity of a model based on HK III, cyclin A and galectin-3. CONCLUSIONS: In this study, we have demonstrated that in addition to galectin-3, HK III and cyclin A profiles could be important biomarkers in predicting malignancy in follicular thyroid nodules. The use of these biomarkers may allow an accurate preoperative diagnosis of thyroid cancer, which can be cost saving and may avoid serious morbidity such as vocal cord paralysis. The value of the suggested biomarkers warrants further evaluation in a large prospective study on cytological samples of follicular thyroid nodules. PMID- 17868401 TI - Combined analysis of intracellular signalling and immunophenotype of human peripheral blood basophils by flow cytometry: a proof of concept. AB - BACKGROUND: The signal transduction pathways and control mechanisms involved in IgE-mediated basophil activation remain incompletely understood. OBJECTIVES: To investigate whether basophilic intracellular signal transduction and immunophenotype can be analysed simultaneously by flow cytometry. METHODS: Basophils in whole blood were stimulated with anti-IgE and latex antigen at various concentrations and during different time courses. Phosphorylation of p38 mitogen-activated protein kinase (MAPK) as a representative of the intracellular signal transduction pathway and surface expression of CD63 was assessed simultaneously flow cytometrically. The effect of pre-incubation with IL-3 was assessed. RESULTS: Stimulation of the basophils with anti-IgE and allergen induces a rapid phosphorylation of p38 MAPK that peaks between 1 and 5 min and returns to baseline levels after 60 min. In contrast, CD63 up-regulation demonstrates a maximal but more continuous expression that peaks approximately 5 min later than phosphorylation of p38 MAPK. Specific inhibition of p38 MAPK reduced or almost completely abrogated up-regulation of CD63. Pre-incubation of the basophils with IL-3 produces a rapid p38 MAPK phosphorylation over basal levels, but this was weaker and shorter than for anti-IgE stimulation. Pre incubation of the basophils with IL-3 did not potentiate anti-IgE-induced phosphorylation of p38 MAPK and did affect spontaneous or IgE-mediated CD63 up regulation. CONCLUSIONS: This study provides the proof that the flow cytometer allows an integrated analysis of basophilic intracellular signalling and immunophenotyping. Owing to its technical simplicity, the low number of cells required and rapid analysis, the technique seems promising for use in the clinic as a diagnostic tool or to monitor therapy. CAPSULE SUMMARY: This study is the first to provide evidence for a combined analysis of basophilic intracellular signalling and immunophenotyping by flow cytometry. Owing to its technical simplicity, the low number of cells required and rapid analysis, the technique seems promising for use in the clinic as a diagnostic tool or to monitor therapy. PMID- 17868402 TI - Comparison of surgical vs chemical sphincterotomy using botulinum toxin for the treatment of chronic anal fissure: a meta-analysis. AB - OBJECTIVE: To analyse systematically prospective randomized controlled trials dealing with the effectiveness of surgical sphincterotomy (SS) vs chemical sphincterotomy (CS) using botulinum toxin for the management of chronic anal fissure (CAF). METHOD: A systematic review of the literature was undertaken. Prospective randomized controlled trials on the effectiveness of SS vs CS using botulinum toxin were selected and analysed to generate the summative outcome. RESULTS: Four prospective randomized controlled trials dealing with SS vs CS using botulinum injection, which included 279 CAF patients, were analysed. Based on the random effects model, there was a higher complication rate [Risk ratio (RR) 14.54 (-9.84, -38.9) 95% CI, df = 2, P < 0.0163] and a higher risk of transient faecal incontinence [RR 6.39 (-2.37, -15.1) 95% CI, df = 3, P < 0.0001] in the SS group than in the CS group. However, there was significant heterogeneity among the trials (Q = 8 408 891, P < 0.0001), indicating a wide confidence interval range; thus, the inferiority of SS could not be shown. SS had a significantly higher healing rate [RR 1.63, (1.34-1.91) 95% CI, df = 3, P < 0.0110] and a significantly lower recurrence rate [RR 0.35 (0.33-0.38) 95% CI, df = 3, P < 0.0221] than CS. CONCLUSION: Both CS and SS are comparable in the management of CAF. There are no differences in the complication rates and incontinence rates between the two procedures. SS has a higher healing rate and a lower recurrence rate than CS. As long as the patient is willing to accept a negligible risk of transient faecal incontinence, SS should be the first-line treatment for CAF. PMID- 17868403 TI - Botulinum toxin vs glyceryltrinitrate for the medical management of chronic anal fissure: a meta-analysis. AB - OBJECTIVE: The objective of this review was to analyse systematically the prospective randomized controlled trials on the effectiveness of botulinum toxin (BTX) and glyceryltrinitrate (GTN) for the pharmacological management of chronic anal fissure (CAF). METHOD: A systematic review of the literature was undertaken. Prospective randomized controlled trials on the effectiveness of BTX and GTN for the management of CAF were selected according to specific criteria and analysed to generate summative data. RESULTS: Six studies encompassing 355 patients with CAF were retrieved from electronic databases. Only three randomized controlled trials on 180 patients qualified for the meta-analysis according to inclusion criteria. There were 90 patients in BTX and 90 in the GTN group. BTX and GTN were equally effective in healing/improving the CAF. There was no statistically significant difference between the two pharmacotherapies [RR 1.29 (0.98-1.70) 95% CI, z = -1.83, P = 1.93, Fig. 1]. However, there was statistically significant heterogeneity among the trials (Q = 4.03, df = 1, P = 0.042). On fixed effect model, GTN was associated with higher incidence of total side effects [fixed effect model RR 0.14 (0.05-0.40) 95% CI, z = -3.71, P = 0.0002] and headache [RR 0.07 (0.02-0.20) 95% CI, z = -5.05, P = 0.0007] among patients of CAF. CONCLUSION: Botulinum toxin is as effective as GTN for the management of CAF but it is associated with a lower complication rate. BTX can be recommended as a first-line therapy for chemical sphincterotomy in patients of CAF. However, a major and multi-centre randomized controlled trial is required to support this treatment approach in order to establish stronger evidence. PMID- 17868404 TI - A randomized controlled trial comparing the efficacy and acceptability of phospo soda buffered saline (Fleet) with sodium picosulphate/magnesium citrate (Picoprep) in the preparation of patients for colonoscopy. AB - OBJECTIVE: Small-volume bowel preparations for colonoscopy has become increasingly popular due to improved tolerance by patients and equivalent efficacy compared with the larger volume preparations. Comparative studies, however, between small volume preparations are lacking. This randomized controlled trial aimed at comparing the efficacy and acceptability of phospo-soda buffered saline (Fleet) with sodium picosulphate/magnesium citrate (Picoprep) in the preparation of patients for colonoscopy. METHOD: A randomized prospective trial designed to compare the efficacy and acceptability of Fleet with Picoprep in patients undergoing colonoscopy. RESULTS: Seventy-three patients undergoing colonoscopy were randomized to receive either Fleet or Picoprep as bowel preparation. Patients were asked to score the acceptability and to comment specifically on adverse events, namely headache, nausea and vomiting. The efficacy of the preparation was also assessed. The results showed no difference in efficacy (P = 0.06, chi(2) test), but there was a significant difference in acceptability (P = 0.01, chi(2) test). and side effects of patients suffering nausea (P = 0.003, chi(2) test), in favour of Picoprep. CONCLUSION: Whilst there was no difference in efficacy, there was a significant difference in acceptability and side effects in favour of Picoprep. PMID- 17868405 TI - Primary anal pilonidal disease. PMID- 17868406 TI - The diagnostic value of digital rectal examination in primary care for palpable rectal tumour. AB - BACKGROUND: Accurate digital rectal examination (DRE) enables the early diagnosis of palpable rectal tumour. We aimed at evaluating the diagnostic value of DRE performed by general practitioners (GPs), with respect to detecting the presence of a palpable rectal tumour. METHOD: All patients diagnosed to have a palpable rectal tumour via a 14-day cancer referral system between May and December 2006 were identified from the colorectal database. Patients referred by GPs during the same period as having a palpable rectal tumour were also identified by reviewing the 14-day cancer referrals. Sensitivity, specificity, positive and negative predictive value of a DRE in primary care were calculated by using these data. RESULTS: Between May and December 2006, 1069 patients were referred to the University Hospital of North Staffordshire to the 14-day urgent colorectal cancer referral service. Of these, 108 patients were referred as having a 'palpable rectal tumour'. Only 32 of the 108 were found to have a rectal lesion on examination in the hospital. Ten tumours were missed by GPs' DREs. CONCLUSION: Digital rectal examination in primary care for palpable rectal tumour has a sensitivity of 0.762, specificity of 0.917, positive predictive value of 0.296 and negative predictive value of 0.988. It is an inaccurate procedure and a poor predictor for palpable rectal tumour. PMID- 17868407 TI - Colpocystodefecography in obstructed defecation: is it really useful to the surgeon? Correlating clinical and radiological findings in surgery for obstructed defecation. AB - OBJECTIVE: Colpocystodefecography images the pelvic floor with the dynamics of defecation, but various authors claim that it overestimates clinical findings. The aim of this study was to evaluate the pre- and postoperative consistency between clinical and colpocystodefecographic findings in patients undergoing surgery for obstructed defecation. METHOD Between June 2001 and September 2003, 20 patients underwent transvaginal posterior colpoperineorrhaphy and rectal mucosal prolapsectomy with one circular stapler for symptomatic rectocele and concomitant anorectal prolapse. They were prospectively evaluated both before surgery by designed questionnaire on constipation and incontinence, proctological, gynaecological and urological examinations, colpocystodefecography and anorectal manometry, and after operation at 6 months by questionnaire and a proctological check-up. The mean follow-up was 30 months (24-48 months). RESULTS: At 6 months the questionnaire revealed a major response in terms of symptoms. The proctological visit confirmed the absence of rectocele in 19 (95%) patients, while the anorectal prolapse had completely disappeared in 17 (85%) patients. Postoperative colpocystodefecography demonstrated a general reduction in the dimensions of the rectocele, which had completely disappeared in five (25%) patients; 40% of the patients had a persistent anorectal prolapse. CONCLUSION: Preoperative data analysis showed a statistically significant correlation between clinical and radiological findings. Postoperatively the global clinical assessment correlated well with patient satisfaction, while there was evidence of a statistically significant difference between the radiological and clinical findings. Routine postoperative use of colpocystodefecography is unjustified unless there is clinical evidence of surgical failure. PMID- 17868408 TI - Strategy in clinical practice for classification of unselected colorectal tumours based on mismatch repair deficiency. AB - OBJECTIVE: Deficiency of DNA mismatch repair (MMR) causes microsatellite instability (MSI) in a subset of colorectal cancers. Patients with these tumours have a better prognosis and may have an altered response to chemotherapy. Some of the tumours are caused by hereditary mutations (hereditary nonpolyposis colon cancer or Lynch syndrome), but most are epigenetic changes of sporadic origin. The aim of this study was to define a robust and inexpensive strategy for such classification in clinical practice. METHOD: Tumours and blood samples from 262 successive patients with colorectal adenocarcinomas were collected. Expression of the MMR proteins MLH1, MSH2, and MSH6 by immunohistochemistry (IHC) was compared with MSI DNA analysis. Methylation analysis of MLH1 and mutation analysis for BRAF V600E were compared in samples with MSI and/or lack of MLH1 expression to determine if the tumour was likely to be sporadic. RESULTS: Thirty-nine (14.9%) of the tumours showed MMR deficiency by IHC or by microsatellite analysis. Sporadic inactivation by methylation of MLH1 promoter was found in 35 patients whereby the BRAF activating V600E mutation, indicating sporadic origin, was found in 32 tumours. On the basis of molecular characteristics we found 223 patients with intact MMR, 35 patients with sporadic MMR deficiency, and four patients who were likely to have hereditary MMR deficiency. CONCLUSION: To obtain the maximal benefit for patients and clinicians, MMR testing should be supplemented with MLH1 methylation or BRAF mutation analysis to distinguish sporadic patients from likely hereditary ones. MMR deficient patients with sporadic disease can be reassured of the better prognosis and the likely hereditary cases should receive genetic counselling. PMID- 17868409 TI - Routine interval appendectomy is unnecessary after conservative treatment of appendiceal mass. AB - OBJECTIVE: The traditional management of appendiceal mass is initial conservative treatment followed by interval appendicectomy. Recently interval appendicectomy has been questioned by a growing amount of evidence. The purpose of this study was to clarify the role of interval appendicectomy after successful initial conservative treatment. METHOD: The study included 98 patients with a mass in the right iliac fossa. Four (4%) patients were excluded wing to another diagnosis of appendiceal mass including caecal cancer (two), diverticulitis (one), and Crohn's disease (one). The remaining 94 patients were treated conservatively. Routine interval appendicectomy was not performed after successful conservative treatment. RESULTS: Ultrasound (US)-guided drainage was performed in seven (7.4%) patients. Two were drained surgically because of a persistent abscess despite a previous US-guided drainage. In five (5.3%) patients, a delayed operation was necessary because of complications. One patient developed small bowel obstruction, and in three patients, conservative treatment was unsuccessful with the abscess remaining unresolved. Within 3 months, seven out of the 89 patients were readmitted to hospital with a recurrent mass in two patients and acute appendicitis without a mass in five patients. Six (6.7%) patients were readmitted with recurrent appendicitis after 3 months. The recurrence rate after successful conservative treatment was 14.6%. The majority (nine patients; 10.1%) of the recurrences occurred within the first 6 months, and after 1 year the recurrence rate was very low (two patients; 2.2%). CONCLUSION: Routine interval appendicectomy after initial successful conservative treatment is not justified and should be abandoned. At present, there is no consensus for the management of appendiceal mass. There is, therefore, a need to develop a protocol for the management of this common problem. PMID- 17868410 TI - Palliative surgery for rectal cancer in a national cohort. AB - OBJECTIVE: Whether resection of the primary tumour is of benefit to patients with incurable rectal cancer (RC) remains a matter of debate. In this study we analyse prospectively recorded data from a national cohort. METHOD: Among 4831 patients diagnosed with RC between 1997 and 2001, 838 (17%) patients were treated with palliative surgery. Patients were stratified according to disease stage, age and type of surgery. RESULTS: A significantly longer median survival, 12 (range 10 13) months, was observed in patients treated with resection of the primary tumour compared with 5 (range 4-6) months in patients treated with nonresective procedures (P < 0.001). Median survival in months was significantly (P < 0.001) related to age (13; < 60 years of age, 10; 60 to 69 years, 7; 70 to 79 years, 6; >/= 80 years of age). In patients over 80 years, survival was similar regardless of the treatment. Thirty-day mortality varied from 2.5% to 20%, according to age groups. CONCLUSION: The longer survival observed in patients with resection of the primary tumour may partly be explained by patient selection. Elderly patients (>/= 80 years) had a similar survival, irrespective of resection of the primary tumour or not. Careful consideration of the individual patient, extent of disease and treatment-related factors are important in decision-taking for palliative treatment for patients with advanced RC. PMID- 17868411 TI - Prognostic value of plasma D-dimer levels in patients with colorectal cancer. AB - OBJECTIVE: Plasma D-dimer levels have been shown to be increased in patients with various solid tumours including lung, prostate, cervical, ovarian, breast and colon cancer. The purpose of this prospective study was to estimate the plasma D dimer level of patients with colorectal cancer before surgery and to assess whether it has a prognostic value. METHOD: The study comprised 51 patients with colorectal cancer. Variables including demographic, clinical, operative and pathological findings and routine laboratory tests were recorded. In addition, tumour markers, coagulation tests and plasma D-dimer levels were evaluated. RESULTS: Histological types other than well-differentiated adenocarcinoma, relatively advanced tumour stage and a high preoperative plasma D-dimer level were the prognostic factors that were associated with shorter postoperative survival according to univariate analyses. The presence of vascular invasion was associated with higher preoperative D-dimer levels. However, there was no statistically significant relationship between postoperative survival and the presence of vascular invasion. CONCLUSION: Postoperative survival was significantly shorter in colorectal cancer patients with elevated preoperative D dimer levels. Evaluation of preoperative D-dimer level can be used to predict postoperative survival. PMID- 17868412 TI - Bone cement for control of massive presacral bleeding. PMID- 17868413 TI - Intra-abdominal and gastrointestinal tuberculosis. AB - OBJECTIVE: Reports suggest that the rates of tuberculosis (TB) continue to rise in the UK and throughout the world. The spread of the disease is aided by poverty, overcrowding, co-infection with human immunodeficiency virus and drug resistance. Consistent with the overall trend, intra-abdominal and gastrointestinal (GI) TB rates are rising. Tuberculosis is a treatable disease, whether occurring in the lungs or at extra-pulmonary sites but the nonspecific features of the disease result in difficulty in establishing a diagnosis. In this report, we have concentrated on the benefits and potential pitfalls of diagnostic methods. METHOD: A literature review was performed using the National Library of Medicine's Pubmed Database using the keywords diagnosis, management, abdominal and GI TB. RESULTS: Abdominal TB presents a particular challenge, as the diverse features of the disease do not readily suggest a particular diagnosis and diagnostic delays lead to significant morbidity and mortality. A number of investigative methods have been used to aid in the diagnosis of abdominal and GI TB. CONCLUSION: The nonspecific presentation of abdominal and GI TB present challenges in the diagnosis of this increasingly common disease. A high index of suspicion is an important factor in early diagnosis. After a diagnosis has been established, prompt initiation of treatment helps prevent morbidity and mortality. PMID- 17868414 TI - High animal-fat intake changes the bile-acid composition of bile juice and enhances the development of Barrett's esophagus and esophageal adenocarcinoma in a rat duodenal-contents reflux model. AB - The dietary components responsible for the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remain unclear. Wistar rats were divided into four groups based on their diet: a low soybean-oil diet, a low cow-fat diet, a high soybean-oil diet, and a high cow-fat diet. First, we evaluated the bile acid composition of the bile juice in each group without operation, using high performance liquid chromatography. Because only high cow-fat intake induced changes in the composition of bile acids in bile juice, we then selected animals fed with a low soybean-oil diet and those with a high cow-fat diet to carry out esophago-jejunostomy for reflux of the duodenal contents, and compared sequential morphological changes between these groups up to 30 weeks after surgery. At 30 weeks after surgery, the reflux animals in the high cow-fat group showed a significantly higher incidence of BE and Barrett's dysplasia than those in the low soybean-oil group, and the incidence of EAC in the high cow-fat group was also slightly higher than that in the low soybean-oil group. High dietary animal fat changed the bile-acid composition and increased the concentration of taurine conjugates in the bile juice. These increased bile acids promoted the development of BE and Barrett's dysplasia leading to EAC. PMID- 17868415 TI - A randomized comparison of conventional vs articulating laparoscopic needle drivers for performing standardized suturing tasks by laparoscopy-naive subjects. AB - OBJECTIVES: To compare the efficacy of conventional and articulating laparoscopic needle-drivers for performing standardized laparoscopic tasks by medical students with no previous surgical experience. SUBJECTS AND METHODS: Twenty medical students with no surgical experience were randomly assigned to two equal groups, one using a conventional laparoscopic needle-holder (Karl Storz, Tuttlingen, Germany) and the other using a first-generation articulating laparoscopic needle holder (Cambridge Endo, Framingham, MA, USA). Each student performed a series of four standardized laparoscopic tasks, during which speed and accuracy were assessed. The tasks tested needle passage through rings (1), an oblique running suture model (2), a urethrovesical anastomosis model (3) and a model simulating renal parenchymal reconstruction following partial nephrectomy (4). RESULTS: Tasks 1 and 3 were completed significantly more quickly by those using the conventional instruments (P < 0.05), but there was no statistically significant difference for task 2 and 4 (P > 0.05). Those using conventional instruments were significantly more accurate in all of the tasks than those using the articulated instruments (P < 0.05). CONCLUSIONS: The conventional laparoscopic needle-driver allowed laparoscopy-naive medical students to complete a series of standardized suturing tasks more rapidly and accurately than with the novel articulating needle-driver. Laparoscopic suturing with first-generation articulating needle drivers might be more difficult to learn, secondary to the complexity of physical manoeuvres required for their use. PMID- 17868416 TI - Microarray analysis of exstrophic human bladder smooth muscle. AB - OBJECTIVE: To compare the genetic profiles of 'healthy' bladder smooth muscle cells (SMCs) and exstrophic SMCs (ESMCs) to identify genes that are over- and under-expressed in ESMCs, thus providing a molecular evaluation of the quality and therapeutic potential of ESMC tissue. PATIENTS, MATERIAL AND METHODS: Classical bladder exstrophy is a rare disorder, occurring in 1 in 30,000 live births. Studies have shown that exstrophic bladders are developmentally immature at birth. After surgical closure, the bladder typically undergoes abnormal remodelling (such as over-expression of collagen III) throughout early development. We hypothesized that the predominant genetic differences between normal SMCs and ESMCs are in the developmental genes. This hypothesis was tested by the use of microarray analysis. Bladder SM biopsies were taken from 'healthy' subjects undergoing bladder surgeries for other conditions (for example, urinary reflux) and patients with bladder exstrophy. Cells were expanded in vitro, and total RNA was isolated and hybridized to the Affymetrix U133A GeneChip (Affymetrix Inc., Santa Clara, CA, USA) by the Wake Forest University School of Medicine Affymetrix core facility, using standard protocols. RESULTS: We created a genetic signature consisting of 961 genes that are over-expressed and 432 genes that are under-expressed in ESMCs. Analysis of these signatures identified an over-expression of inflammatory genes and an under-expression of developmental genes. CONCLUSION: Our data is in concordance with previous studies and histological data showing that ESMCs are developmentally immature relative to healthy bladder SM. The clinical implication of the ESMC genetic signature is that it provides a list of targets that can be (i) manipulated ex vivo and/or in vivo to induce differentiation (the completion of development) and (ii) used as biomarkers to explain the variability of the clinical symptoms after surgical closure. PMID- 17868417 TI - Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on testicular spermatogenesis related panels and serum sex hormone levels in rats. AB - OBJECTIVES: To determine the detrimental role of tetrachlorodibenzo-p-dioxin (TCDD) in testicular histology, spermatogenesis-related panels and proteome, and serum sex hormone levels. MATERIALS AND METHODS: In all, 40 male rats were divided into equal groups: a normal control (NC) group that received vehicle and saline, and a TCDD-treated (TT) group injected intraperitoneally with TCDD (one dose, 50 microg/kg body weight). The rats were killed 4 weeks after TCDD exposure and testicular weight, histopathology, proteome and variables related to spermatogenesis, and serum sex hormone levels were investigated. RESULTS: TCDD induced a significant decrease in testicular weight, Johnsen's score, seminiferous tubular size, percentage of tubules containing sperm, sperm counts, germ cell counts and Sertoli cell index. In addition, there was a significant decrease in serum testosterone level (P < 0.01) and a remarkable increase in oestradiol (P < 0.01), follicle-stimulating hormone (P < 0.05) and luteinizing hormone (P < 0.05) levels in the TT group. The expression of six testicular proteins including testis-specific heat shock protein (Hsp70), protein disulphide isomerase A3 precursor, 3-phosphoglycerate dehydrogenase, nonmuscle myosin heavy chain type B-like protein, and superoxide dismutase 1 were significantly up regulated (P < 0.05-0.01). Interestingly, fertility protein SP22 and phosphatidylethanolamine-binding protein were down-regulated but this was only significant for fertility protein SP22 (P < 0.05). CONCLUSION: TCDD induces marked histological changes in the testis, impairs variables related to spermatogenesis, and increases serum oestradiol levels but decreases testosterone levels. In particular, TCDD disturbs testicular proteome profiles in rats. PMID- 17868418 TI - Erythropoietin receptor expression in the human urogenital tract: immunolocalization in the prostate, neurovascular bundle and penis. AB - OBJECTIVE: To investigate whether the erythropoietin (EPO) receptor is expressed in human periprostatic (including the neurovascular bundles) and penile tissues, and define its distribution in these tissues, as the administration of exogenous EPO in cavernous nerve injury promoted the recovery of erectile function in a rat model. MATERIALS AND METHODS: Human prostate (six samples) and penile (two) tissue were collected and paraffin-embedded. Tissue was sectioned and processed for immunohistochemical studies using an antibody for the EPO receptor; immunolocalization was assessed using light microscopy. RESULTS: There was prominent staining for the EPO receptor in neuronal cell bodies of the periprostatic neurovascular bundles, and in the axons emanating from these ganglia. The glandular epithelium of the prostate also had weak staining. There was EPO receptor immunoreactivity in the penile specimens in the penile dorsal nerves, sinusoidal endothelium of the corpus cavernosum, and endothelial cells lining the dorsal veins and arteries. All slides processed with no primary antibody or blocking peptide showed no staining. CONCLUSIONS: EPO receptor expression was identified and localized in human penile tissues and in the periprostatic neurovascular bundles responsible for erectile function. This suggests a likely role for endogenous EPO within these tissues, and provides the rationale for its clinical use as a protective agent locally. PMID- 17868419 TI - Overlap of different urological symptom complexes in a racially and ethnically diverse, community-based population of men and women. AB - OBJECTIVE: To define the prevalence and overlap of symptom patterns traditionally associated with benign prostatic hyperplasia, chronic prostatitis/chronic pelvic pain syndrome, interstitial cystitis/painful bladder syndrome, and incontinence among men and women in a racially and ethnically diverse, community-based population. SUBJECTS AND METHODS: In all, 5506 men and women aged 30-79 years were recruited to participate in the Boston Area Community Health Survey, using a stratified-cluster sampling technique to obtain roughly similar representative samples by age group, gender and race/ethnicity (White, Black, Hispanic). Survey data were collected by bilingual interviewers in subjects' homes. Scales measuring symptom patterns were derived from validated instruments, with minor changes to eliminate different recall periods and overlap in items that might have confused subjects. RESULTS: About a quarter of men and women of all ages met the definition for one or more of the target symptom patterns; there was no significant variation in the prevalence of any of the symptom patterns by race/ethnicity. Overall, approximately 16% of men and women had one symptom pattern, while 7% had overlap patterns. Except for urinary incontinence and interstitial cystitis/painful bladder syndrome in both men and women, the prevalence of all symptom complexes were associated with one another significantly more often that would be expected by chance. CONCLUSIONS: Overlapping patterns of lower urinary tract symptoms and pelvic pain are common. These overlapping patterns present challenges for clinical practice and research, and require further investigation of their causes, diagnosis and optimum treatment. PMID- 17868420 TI - Risk of new-onset diabetes mellitus and worsening glycaemic variables for established diabetes in men undergoing androgen-deprivation therapy for prostate cancer. AB - OBJECTIVE To investigate the incidence of new-onset diabetes mellitus (NODM) and of worsening glycaemic control in established DM after starting androgen deprivation therapy (ADT) for prostate cancer, as ADT is associated with altered body composition, potentially influencing insulin sensitivity. PATIENTS AND METHODS We retrospectively reviewed patients receiving ADT for prostate cancer at our institution between January 1989 and July 2005; those with incomplete information and those receiving only neoadjuvant ADT were excluded. Variables examined included age, race, body mass index (BMI), pretreatment prostate specific antigen, Gleason sum, clinical stage, ADT type (medical vs surgical) and schedule (continuous vs intermittent), presence of pre-existing DM, serum glucose and glycosylated haemoglobin (HbA1c) levels before and after ADT, and receipt of vitamin D or bisphosphonate supplementation. Data were analysed statistically and P < 0.05 considered to indicate significance. RESULTS In all, 396 patients (median age 73.2 years; median BMI of 26.7 kg/m(2) at ADT initiation) were analysed. Of these, 59.1% were African-American and 40.9% were Caucasian/other. At a median follow-up of 60.1 months, 36 (11.3%) patients developed NODM. In 77 patients with pre-existing DM, there was an increase of >/=10% in serum HbA1c or fasting glucose levels in 15 (19.5%) and 22 (28.6%), respectively. On multivariate analysis, a BMI of >/=30 kg/m(2) was associated with an increased risk of developing NODM (odds ratio 4.65, P = 0.031). Receipt of vitamin D had a protective effect (odds ratio 5.75, P = 0.017). CONCLUSIONS Patients receiving ADT for prostate cancer with or with no history of DM should have routine surveillance of glycaemic control, particularly when their BMI is >/= 30 kg/m(2), with appropriate preventive and treatment measures. PMID- 17868421 TI - Non-genomic effects of androgens on isolated human vascular and nonvascular penile erectile tissue. AB - OBJECTIVES: To evaluate non-genomic effects of testosterone and dihydrotestosterone (DHT) on isolated human cavernosal arteries (HCA) and corpus cavernosum (HCC) using organ-bath studies and radio-immunoassays (RIA), as non genomic effects of androgens are reported for vascular smooth musculature and there is evidence that the relaxant response involves a modulation of cyclic nucleotide tissue levels. MATERIALS AND METHODS: The relaxation induced by the cumulative addition of testosterone and DHT (0.01-10 microm) was studied using circular segments of HCA and strip preparations of HCC. To evaluate the effects of testosterone and DHT on tissue levels of cAMP and cGMP, specimens were exposed to increasing concentrations of the hormones. Forskolin and sodium nitroprusside (SNP) served as reference compounds. RESULTS: Testosterone and DHT dose dependently reversed the noradrenaline-induced tension of vascular segments and HCC strips. At the maximum concentration, testosterone and DHT reduced the mean (sd) tension to 79.8 (4.43)% and 83.9 (10.94)%, respectively. SNP and forskolin significantly stimulated the production of cGMP and cAMP. No effects of testosterone and DHT on cGMP and cAMP levels were detected. CONCLUSION: Rapid androgen-induced relaxation of HCA and HCC occurs via non-genomic mechanisms. In penile erectile tissue, non-genomic relaxant effects of testosterone and DHT are not mediated via modulation of cyclic nucleotide tissue levels. Additional studies are required to establish if non-genomic relaxant effects are important in ensuring a basal level of perfusion to maintain overall penile function. PMID- 17868422 TI - Prognostic value of syndecan-1 expression in patients treated with radical prostatectomy. AB - OBJECTIVE: To investigate the association of syndecan-1 expression with pathological features and disease progression in patients treated with radical prostatectomy (RP) as syndecan-1 plays a role in the regulation of cell proliferation, migration, and differentiation and its expression is altered in various malignancies. PATIENTS AND METHODS: Syndecan-1 immunostaining was performed on a tissue microarray containing cores from 232 consecutive patients treated with RP and bilateral lymphadenectomy for clinically localized prostatic adenocarcinoma. Patients were categorized as having features of aggressive progression if they had evidence of metastases, an after progression prostate specific antigen (PSA) doubling time of < 10 months, and/or failure to respond to local salvage radiation therapy. Expression was defined as > or = 10% cells staining for syndecan-1. RESULTS: Syndecan-1 was expressed in 86 patients (37.1%). Expression of syndecan-1 was associated with higher PSA levels (P = 0.004), higher pathological Gleason sum (P = 0.027) and lymph nodes metastases (P = 0.027). Patients with syndecan-1 expression were at significantly greater risk of PSA-progression after surgery (P = 0.034) in univariate but not in multivariate analysis. Patients with features of aggressive progression (n = 22) were more likely to express syndecan-1 than those with features of nonaggressive progression (63.6% vs 36.4%, P = 0.010). Patients with syndecan-1 expression were at significantly greater risk of aggressive progression after surgery (P = 0.005) in univariate but not in multivariate analysis. CONCLUSIONS: Expression of syndecan-1 was associated with established features of biologically aggressive prostate cancer and PSA-progression in univariate analysis. These findings suggest a role for syndecan-1 in prostate carcinogenesis and progression. PMID- 17868423 TI - Total or partial prostate sparing cystectomy for invasive bladder cancer: long term implications on erectile function. AB - OBJECTIVE: To review the long-term results in patients treated with either total or partial prostate-sparing cystectomy, focusing on erectile function (EF), as en bloc radical cystectomy (RC) with or without urethrectomy has been the method of choice for managing invasive bladder carcinoma, but has inherent risks of subsequent urinary incontinence and erectile dysfunction, with a marked effect on quality of life, especially in younger patients. PATIENTS AND METHODS: Between 2003 and 2005 we assessed 21 men (mean age 56 years) who had either a prostate apex-sparing cystectomy (PASC, 15) or total prostate-sparing cystectomy (TPSC, six). The mean follow-up was 30 months for PASC and 24 months for TPSC. The evaluation before surgery included standard bladder cancer staging, prostate specific antigen level, a digital rectal examination and a complete medical history, with attention to self-reported EF before surgery and the EF domain of the International Index of EF (IIEF) after surgery. RESULTS: The EF domain score was 20 after PASC and 30 after TPSC; this correlates with mild to moderate ED in the PASC group vs normal erectile function in the TPSC group. After transurethral resection of the bladder tumours (TURBT) 10 of 14 in the PASC group were T1 or T2a, and in the TPSC group, five of six were T2a and one patient was T2b. From the cystectomy specimen, in the PASC group eight were understaged compared with the TURBT specimen (T2b/T4a vs T1/T2a), while in the TPSC group there was understaging two (T3a vs T2a/T2b); this was significantly different (P < 0.05). There was recurrence of urothelial carcinoma in one of 15 and one of six after PASC and TPSC, respectively. CONCLUSION: The EF domain score after PASC was 10 points lower than after TPSC, representing a 30% increase in EF by preserving the entire prostate. We conclude that in patients with invasive bladder cancer, EF can be significantly preserved by prostate-sparing cystectomy. If adequate selection criteria are applied, EF can be preserved without compromising cancer control. PMID- 17868424 TI - Influence of the glycosaminoglycan layer on the permeation of hypericin in rat bladders in vivo. AB - OBJECTIVE: To investigate the influence of a glycosaminoglycan (GAG) layer on the specific location of hypericin in superficial urothelial carcinoma lesions of the bladder after intravesical instillation. MATERIALS AND METHODS: Fisher rat bladders were incubated with 15 or 30 microm hypericin for 2 h. To examine the influence of the GAG layer on the permeation of hypericin, bladders were pre treated with chondroitinase ABC, n-dodecyl-beta-d-maltoside (DDM) or sodium dodecyl sulphate (SDS) to disrupt, or protamine to neutralise the GAG layer before incubating with hypericin. After incubation, the photosensitizer permeation was examined quantitatively in cryostat sections of the bladders, using fluorescence microscopy and image analysis. RESULTS: Disrupting or neutralising the GAG layer in the bladder had no influence on the permeation of hypericin. Pre-treatment of the bladder with chondroitinase, DDM or SDS resulted in a significantly lower accumulation of hypericin, whereas neutralising the GAG layer in rats with protamine had no significant effect on the biodistribution of hypericin. CONCLUSION: The GAG matrix causes no obstacle to the permeation of hypericin in the urothelium of the bladder, and modification of this GAG layer cannot explain the enhanced accumulation of hypericin in superficial bladder tumours. PMID- 17868425 TI - Transobturator surgery for female stress incontinence: a comparative anatomical study of outside-in vs inside-out techniques. AB - OBJECTIVE To assess the specific risks of injury to neural and vascular structures inherent in two approaches to transobturator surgery for inserting a suburethral sling, i.e. the outside-in (standard technique) and inside-out approaches. MATERIALS AND METHODS The study comprised seven cadavers, providing 14 obturator regions. Five specimens had a tape inserted outside-in on one side, and inside-out on the other; of the remaining two cadavers, one had an inside-out tape and one an outside-in tape, bilaterally. After tape insertion, the cadavers were dissected. Particular attention was paid to the distances between the tape and the deep external pudendal vessels, and between the tape and the posterior branch of the obturator nerve. RESULTS With the inside-out technique, the safety margins were reduced, and the external pudendal vessels and the posterior branch of the obturator nerve were at greater risk of injury. CONCLUSION The two techniques are not equivalent, with a lower risk of injury to vascular and nerve structures with the outside-in technique. PMID- 17868426 TI - The associations among eNOS G894T gene polymorphism, erectile dysfunction and related risk factors. AB - OBJECTIVE: To investigate the possible correlations among eNOS G894T polymorphism, erectile dysfunction (ED) and related risk factors in a Taiwanese population. MATERIALS AND METHODS: In all, 151 patients with ED and 77 healthy controls were enrolled. All the men had a complete clinical history taken and laboratory data was collected. To assess erectile conditions the five-item version of the International Index of Erectile Function (IIEF-5) was used. The eNOS G894T polymorphisms were determined using the polymerase chain reaction restriction fragment length polymorphism method. RESULTS: In all, 228 men were enrolled with a mean (sd) age of 58.6 (9.7) years. In a univariate analysis, age, serum testosterone level, and the prevalence of diabetes mellitus (DM) and hypertension were significantly different between patients with ED and the healthy controls (P < 0.01). In the multiple logistic regression analysis, DM, age and hypogonadism were three independent risk factors for ED (P = 0.018, P = 0.046 and P = 0.016, respectively). The prevalence of ED in T allele carriers (GT/TT) was significantly greater than in G allele carriers (GG; 80.0% vs 63.3%, P = 0.04). Also the eNOS 894T allele carriers had significantly lower IIEF-5 scores than the eNOS 894G allele carriers, at 13.2 (5.3) vs 15.7 (6.1) (P = 0.01) and it was associated with increment of T allele number (11.0 (5.6) vs 13.6 (5.2) vs 15.7 (6.1); P = 0.03). CONCLUSION: Our results indicate that DM, age and hypoganadism are three significant independent risk factors for ED. Also, in the Taiwanese population, the eNOS 894T allele carriers are at greater risk of ED, both in prevalence and severity, and this might be a factor of genetic susceptibility. PMID- 17868427 TI - Laparoscopic reconstructive options for obstruction in children with duplex renal anomalies. AB - OBJECTIVE: To present our initial experience of laparoscopic reconstructive surgery in children with upper urinary tract obstruction associated with duplex anomalies, as although there is much information on ablative procedures such as laparoscopic heminephrectomy, there is little available about minimally invasive reconstructive options for duplex renal anomalies in children. PATIENTS AND METHODS: We retrospectively reviewed four consecutive patients (aged 6-11 years) with duplex anomalies and laparoscopic reconstruction for obstructed, dilated segments treated at our institution. The port placement and surgical exposure were analogous to that for transperitoneal laparoscopic pyeloplasty. A JJ stent was placed retrogradely into the ureter immediately before each procedure. The procedures performed were pyelo-ureterostomy for incomplete duplication and lower pole pelvi-ureteric junction (PUJ) obstruction, lower pole pyeloplasty for lower pole PUJ obstruction and complete duplication, and ipsilateral uretero ureterostomy and distal ureterectomy for an obstructed, ectopic upper pole. Foley catheters were left indwelling for 36-48 h and stents were removed at 4-6 weeks. Postoperative imaging included either ultrasonography or intravenous urography. RESULTS: Three children presented with intermittent flank pain due to lower pole PUJ obstruction. The other child presented with pyonephrosis and purulent drainage from her vagina due to an ectopic ureter associated with a functioning upper pole segment. All procedures were successfully completed. The only complication was in the first patient (pyelo-ureterostomy) who had transient urinary extravasation that resolved with bladder decompression for 10 days. With a follow-up of 6-18 months, all had resolution of symptoms with improvement in radiographic variables. CONCLUSIONS: This series shows that children with duplex anomalies and obstruction can undergo successful reconstruction using techniques learned with laparoscopic pyeloplasty. PMID- 17868428 TI - Subjective response and attitudes toward antipsychotic drug therapy during the initial treatment period: a prospective follow-up study in patients with schizophrenia. AB - OBJECTIVE: In this prospective study, patients with schizophrenia were followed up for 3 months to investigate the impact of sociodemographic factors, psychopathology, change in psychopathology and side effects on subjective response and attitudes toward antipsychotics during the initial treatment period. METHOD: We investigated 42 patients starting treatment with a new-generation antipsychotic. Next to the registration of demographic data various rating scales were used: the Positive and Negative Syndrome Scale (PANSS), the Udvalg for Kliniske Undersogelser (UKU) Side Effect Rating Scale and the Drug Attitude Inventory (DAI). RESULTS: Two patients experienced a first episode of the illness and were neuroleptic naive, and 40 had suffered from at least one prior episode of schizophrenia. Longer duration of illness as well as the amelioration of psychopathological symptoms had a positive impact on subjective response to treatment. Correlations between antipsychotic-induced side effects and drug attitude tended to be weak. CONCLUSION: Our results emphasize the necessity of improving psychopathological symptoms during the initial treatment period to improve attitudes toward and compliance with treatment. PMID- 17868429 TI - Predictors of violent victimization amongst those with psychosis. AB - OBJECTIVE: The aim of this study was to establish the prevalence and predictors of violent victimization amongst a community-dwelling sample of individuals with psychosis. METHOD: The 2-year prevalence of self-reported violent victimization was estimated for a sample of 708 individuals with chronic psychosis living in the community in four urban UK centres. Baseline socio-demographic and clinical factors were examined as possible risk factors for victimization over the 2-year follow-up period. RESULTS: The 2-year prevalence of violent victimization in the sample was 23%. Four factors were found to be independently predictive of victimization - history of victimization, less than daily family contact, young age at illness onset and the presence of co-morbid Cluster B personality disorder. CONCLUSION: Those with psychotic illnesses are at elevated risk of being assaulted. Given the likely adverse health implications, clinicians should routinely enquire about victimization in their assessments of those with psychotic disorders particularly amongst those who are socially isolated, with a younger age of illness onset and in those with co-morbid personality disorder. PMID- 17868430 TI - The efficacy and safety of apixaban, an oral, direct factor Xa inhibitor, as thromboprophylaxis in patients following total knee replacement. AB - BACKGROUND: Heparins and warfarin are currently used as venous thromboembolism (VTE) prophylaxis in surgery. Inhibition of factor (F) Xa provides a specific mechanism of anticoagulation and the potential for an improved benefit-risk profile. OBJECTIVES: To evaluate the safety and efficacy of apixaban, a potent, direct, oral inhibitor of FXa, in patients following total knee replacement (TKR), and to investigate dose-response relationships. PATIENTS/METHODS: A total of 1238 patients were randomized to one of six double-blind apixaban doses [5, 10 or 20 mg day(-1) administered as a single (q.d.) or a twice-daily divided dose (b.i.d.)], enoxaparin (30 mg b.i.d.) or open-label warfarin (titrated to an International Normalized Ratio of 1.8-3.0). Treatment lasted 10-14 days, commencing 12-24 h after surgery with apixaban or enoxaparin, and on the evening of surgery with warfarin. The primary efficacy outcome was a composite of VTE (mandatory venography) and all-cause mortality during treatment. The primary safety outcome was major bleeding. RESULTS: A total of 1217 patients were eligible for safety and 856 patients for efficacy analysis. All apixaban groups had lower primary efficacy event rates than either comparator. The primary outcome rate decreased with increasing apixaban dose (P = 0.09 with q.d./b.i.d. regimens combined, P = 0.19 for q.d. and P = 0.13 for b.i.d. dosing).A significant dose-related increase in the incidence of total adjudicated bleeding events was noted in the q.d. (P = 0.01) and b.i.d. (P = 0.02) apixaban groups; there was no difference between q.d. and b.i.d. regimens. CONCLUSIONS: Apixaban in doses of 2.5 mg b.i.d. or 5 mg q.d. has a promising benefit-risk profile compared with the current standards of care following TKR. PMID- 17868431 TI - Review article: the assessment of liver function using breath tests. AB - BACKGROUND: Hepatologists have long sought to develop a test for assessing liver function, but this aim has been stalled by the complexity of the liver and its diverse functions. Results of metabolic tests, including breath tests, correlate with clinical and histological parameters of patients with liver disorders; however, these tests tend to be cumbersome and impractical for everyday use. The recent development of a real-time, point-of-care liver function breath test has made it straightforward to assess the metabolic function of the liver. AIM: To review the available data on the use of breath tests for assessing liver reserve in various conditions and their application in various clinical hepatology settings. RESULTS: The (13)C-methacetin breath test enables accurate follow-up of patients with acute or chronic liver damage, where overall hepatic function is significantly suppressed by known causes of liver disorders, including acute, sub acute or chronic conditions. The metabolic breath test can detect both gradual and spontaneous improvements in liver function and the effects of treatment. CONCLUSIONS: Breath testing that provides continuous quantification of methacetin metabolism may be a sensitive tool for the diagnosis and follow-up of patients with liver disorders. PMID- 17868432 TI - Costs and thresholds in cost-effectiveness analysis. PMID- 17868433 TI - Review article: vaccination and viral hepatitis - current status and future prospects. AB - BACKGROUND: Viral hepatitis is the most common cause of liver disease in the world. In the past 25 years, vaccines have become available for two of the five hepatitis viruses, and, where implemented, vaccination has become a key component of hepatitis prevention. AIMS: To provide an update on recent advances in the use of current hepatitis vaccines and to examine progress in the development of vaccines for the remaining hepatitis viruses. METHODS: A Medline search was undertaken to identify the recent relevant literature. Search terms included hepatitis vaccines, hepatitis vaccination and hepatitis A-E vaccines. RESULTS: Dramatic vaccine-induced declines in the incidence of both hepatitis A and B have occurred in the USA. Strategies to integrate hepatitis A vaccine into universal childhood immunization are being adopted. Similarly, strategies with the goal of eliminating transmission of hepatitis B have been promulgated. A vaccine for hepatitis E has been reported to be effective and safe, but progress in the development of vaccines for hepatitis C and D has been limited. CONCLUSION: During the next few decades, the goals of eliminating hepatitis A and B virus transmission may be reached in the USA and elsewhere. PMID- 17868434 TI - Susceptibility of schizophrenia and affective disorder not associated with loci on chromosome 6q in Han Chinese population. AB - BACKGROUND: Several linkage studies across multiple population groups provide convergent support for susceptibility loci for schizophrenia - and, more recently, for affective disorder - on chromosome 6q. We explore whether schizophrenia and affective disorder have common susceptibility gene on 6q in Han Chinese population. METHODS: In the present study, we genotyped 45 family trios from Han Chinese population with mixed family history of schizophrenia and affective disorder. Twelve short tandem repeat (STRs) markers were selected, which covered 102.19 cM on chromosome 6q with average spacing 9.29 cM and heterozygosity 0.78. The transmission disequilibrium test (TDT) was performed to search for susceptibility loci to schizophrenia and affective disorder. RESULTS: The results showed STRs D6S257, D6S460, D6S1021, D6S292 and D6S1581 were associated with susceptibility to psychotic disorders. When families were grouped into schizophrenia and affective disorder group, D6S257, D6S460 and D6S1021, which map closely to the centromere of chromosome 6q, were associated with susceptibility to schizophrenia. Meanwhile, D6S1581, which maps closely to the telomere, was associated with susceptibility to affective disorder. But after correction of multiple test, all above association were changed into no significance (P > 0.05). CONCLUSION: These results suggest that susceptibility of schizophrenia and affective disorder not associated with loci on chromosome 6q in Han Chinese population. PMID- 17868435 TI - Towards a possible aetiology for depressions? AB - BACKGROUND: Since a genetic disposition for depression is probable, there ought to be biochemical changes. Increased peptide levels with relevant bioactivities have been found in urine in a previous investigation, which may be such changes. METHODS: Urine from patients with severe depression according to ICD 10 have been run on reversed phase High Performance Liquid Chromatography, and off line mass spectrometry was performed on some of these peptides. RESULTS: We find overlapping patterns of peptide peaks in severe depression, but with considerable individuality. Mass spectrometry shows that some of these peptides are probably of dietary origin, because their sequences are found only in certain dietary proteins. Opioids from casein and gliadin are typical examples. CONCLUSION: Our data show that the disposition must be polygenetic because some peptide peaks with the same bioactivity are of different length in different patients, but with the same diagnosis. However, some of the peaks are common Peptide increase in urine is found when break down is deficient, and the data presented agree with reports on peptidase deficiencies in depression. Antidepressant drugs decrease the peptide level after about 3 weeks. PMID- 17868437 TI - Combined endocrine and exocrine tumours of the pancreas. AB - BACKGROUND: Cystic neoplasms of the pancreas comprise 10%-15% of pancreatic cystic lesions, with the serous cystadenoms being the commonest. The association of exocrine and endocrine tumours of the pancreas unrelated to Von Hipple Lindau disease is very rare. Very few cases have been reported in the literature. We present another case of both these tumours in one patient. CASE PRESENTATION: A female patient was seen in the surgical clinic for a pain in the right groin. Clinical examination and investigations confirmed a diagnosis of combined endocrine and exocrine tumours of the pancreas. She underwent surgery and is under regular follow-up in the surgical clinic. CONCLUSION: Biphasic differentiation of pancreatic stem cell during embryological development could happen and may result in combined endocrine and exocrine tumours of the pancreas. Imaging studies are excellent in diagnosing theses lesions. Surgery has a central role and could be curative. PMID- 17868436 TI - Rationale, design, and protocol for the prevention of low back pain in the military (POLM) trial (NCT00373009). AB - BACKGROUND: There are few effective strategies reported for the primary prevention of low back pain (LBP). Core stabilization exercises targeting the deep abdominal and trunk musculature and psychosocial education programs addressing patient beliefs and coping styles represent the current best evidence for secondary prevention of low back pain. However, these programs have not been widely tested to determine if they are effective at preventing the primary onset and/or severity of LBP. The purpose of this cluster randomized clinical trial is to determine if a combined core stabilization exercise and education program is effective in preventing the onset and/or severity of LBP. The effect of the combined program will be compared to three other standard programs. METHODS/DESIGN: Consecutive Soldiers participating in advanced individual training (AIT) will be screened for eligibility requirements and consented to study participation, as appropriate. Companies of Soldiers will be randomly assigned to receive the following standard prevention programs; a core stabilization exercise program (CSEP) alone, a CSEP with a psychosocial education (PSEP), a traditional exercise (TEP), or a TEP with a PSEP. Proximal outcome measures will be assessed at the conclusion of AIT (a 12 week training period) and include imaging of deep lumbar musculature using real-time ultrasound imaging and beliefs about LBP by self-report questionnaire. We are hypothesizing that Soldiers receiving the CSEP will have improved thickness of selected deep lumbar musculature (transversus abdominus, multifidi, and erector spinae muscles). We are also hypothesizing that Soldiers receiving the PSEP will have improved beliefs about the management of LBP. After AIT, Soldiers will be followed monthly to measure the distal outcomes of LBP occurrence and severity. This information will be collected during the subsequent 2 years following completion of AIT using a web-based data entry system. Soldiers will receive a monthly email that queries whether any LBP was experienced in the previous calendar month. Soldiers reporting LBP will enter episode-specific data related to pain intensity, pain related disability, fear-avoidance beliefs, and pain catastrophizing. We are hypothesizing that Soldiers receiving the CSEP and PSEP will report the longest duration to first episode of LBP, the lowest frequency of LBP, and the lowest severity of LBP episodes. Statistical comparisons will be made between each of the randomly assigned prevention programs to test our hypotheses related to determining which of the 4 programs is most effective. DISCUSSION: We have presented the design and protocol for the POLM trial. Completion of this trial will provide important information on how to effectively train Soldiers for the prevention of LBP. PMID- 17868438 TI - The extracellular leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns. AB - BACKGROUND: Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development. Here we catalogue all of the extracellular LRR (eLRR) proteins in worms, flies, mice and humans. We use convergent evidence from several transmembrane-prediction and motif-detection programs, including a customised algorithm, LRRscan, to identify eLRR proteins, and a hierarchical clustering method based on TribeMCL to establish their evolutionary relationships. RESULTS: This yields a total of 369 proteins (29 in worm, 66 in fly, 135 in mouse and 139 in human), many of them of unknown function. We group eLRR proteins into several classes: those with only LRRs, those that cluster with Toll-like receptors (Tlrs), those with immunoglobulin or fibronectin-type 3 (FN3) domains and those with some other domain. These groups show differential patterns of expansion and diversification across species. Our analyses reveal several clusters of novel genes, including two Elfn genes, encoding transmembrane proteins with eLRRs and an FN3 domain, and six genes encoding transmembrane proteins with eLRRs only (the Elron cluster). Many of these are expressed in discrete patterns in the developing mouse brain, notably in the thalamus and cortex. We have also identified a number of novel fly eLRR proteins with discrete expression in the embryonic nervous system. CONCLUSION: This study provides the necessary foundation for a systematic analysis of the functions of this class of genes, which are likely to include prominently innate immunity, inflammation and neural development, especially the specification of neuronal connectivity. PMID- 17868439 TI - Tagging of MADS domain proteins for chromatin immunoprecipitation. AB - BACKGROUND: Most transcription factors fulfill their role in complexes and regulate their target genes upon binding to DNA motifs located in upstream regions or introns. To date, knowledge about transcription factor target genes and their corresponding transcription factor binding sites are still very limited. Two related methods that allow in vivo identification of transcription factor binding sites are chromatin immunoprecipitation (ChIP) and chromatin affinity purification (ChAP). For ChAP, the protein of interest is tagged with a peptide or protein, which can be used for affinity purification of the protein DNA complex and hence, the identification of the target gene. RESULTS: Here, we present the results of experiments aiming at the development of a generic tagging approach for the Arabidopsis MADS domain proteins AGAMOUS, SEPALLATA3, and FRUITFULL. For this, Arabidopsis wild type plants were transformed with constructs containing a MADS-box gene fused to either a double Strep-tag II-FLAG tag, a triple HA-tag, or an eGFP-tag, all under the control of the constitutive double 35S Cauliflower Mosaic Virus (CaMV) promoter. Strikingly, in all cases, the number of transformants with loss-of-function phenotypes was much larger than those with an overexpression phenotype. Using endogenous promoters in stead of the 35S CaMV resulted in a dramatic reduction in the frequency of loss-of function phenotypes. Furthermore, pleiotropic defects occasionally caused by an overexpression strategy can be overcome by using the native promoter of the gene. Finally, a ChAP result is presented using GFP antibody on plants carrying a genomic fragment of a MADS-box gene fused to GFP. CONCLUSION: This study revealed that MADS-box proteins are very sensitive to fusions with small peptide tags and GFP tags. Furthermore, for the expression of chimeric versions of MADS-box genes it is favorable to use the entire genomic region in frame to the tag of choice. Interestingly, though unexpected, it appears that the use of chimeric versions of MADS-box genes under the control of the strong 35S CaMV promoter is a very efficient method to obtain dominant-negative mutants, either caused by cosuppression or by alteration of the activity of the recombinant protein. Finally, we were able to demonstrate AGAMOUS binding to one of its targets by ChAP. PMID- 17868440 TI - Molecules, morphometrics and new fossils provide an integrated view of the evolutionary history of Rhinopomatidae (Mammalia: Chiroptera). AB - BACKGROUND: The Rhinopomatidae, traditionally considered to be one of the most ancient chiropteran clades, remains one of the least known groups of Rhinolophoidea. No relevant fossil record is available for this family. Whereas there have been extensive radiations in related families Rhinolophidae and Hipposideridae, there are only a few species in the Rhinopomatidae and their phylogenetic relationship and status are not fully understood. RESULTS: Here we present (a) a phylogenetic analysis based on a partial cytochrome b sequence, (b) new fossils from the Upper Miocene site Elaiochoria 2 (Chalkidiki, Greece), which represents the first appearance datum of the family based on the fossil record, and (c) discussion of the phylogeographic patterns in both molecular and morphological traits. We found deep divergences in the Rhinopoma hardwickii lineage, suggesting that the allopatric populations in (i) Iran and (ii) North Africa and the Middle East should have separate species status. The latter species (R. cystops) exhibits a shallow pattern of isolation by distance (separating the Middle East and the African populations) that contrasts with the pattern of geographic variation in the morphometrical traits. A deep genetic gap was also found in Rhinopoma muscatellum (Iran vs. Yemen). We found only minute genetic distance between R. microphyllum from the Levant and India, which fails to support the sub/species distinctness of the Indian form (R. microphyllum kinneari). CONCLUSION: The mtDNA survey provided phylogenetic tree of the family Rhinopomatidae for the first time and revealed an unexpected diversification of the group both within R. hardwickii and R. muscatellum morphospecies. The paleobiogeographic scenario compiled in respect to molecular clock data suggests that the family originated in the region south of the Eocene Western Tethyan seaway or in India, and extended its range during the Early Miocene. The fossil record suggests a Miocene spread into the Mediterranean region, followed by a post-Miocene retreat. Morphological analysis compared with genetic data indicates considerable phenotypic plasticity in this group. PMID- 17868441 TI - Dynamics of C-reactive protein and white blood cell count in critically ill patients with nosocomial Gram positive vs. Gram negative bacteremia: a historical cohort study. AB - BACKGROUND: Nosocomial bacteremia is associated with a poor prognosis. Early adequate therapy has been shown to improve outcome. Consequently, rapid detection of a beginning sepsis is therefore of the utmost importance. This historical cohort study was designed to evaluate if different patterns can be observed in either C-reactive protein (CRP) and white blood cell count (WCC) between Gram positive bacteremia (GPB) vs. Gram negative bacteremia (GNB), and to assess the potential benefit of serial measurements of both biomarkers in terms of early antimicrobial therapy initiation. METHODS: A historical study (2003-2004) was conducted, including all adult intensive care unit patients with a nosocomial bacteremia. CRP and WCC count measurements were recorded daily from two days prior (d(-2)) until one day after onset of bacteremia (d(+1)). Delta (Delta) CRP and Delta WCC levels from the level at d-2 onward were calculated. RESULTS: CRP levels and WCC counts were substantially higher in patients with GNB. Logistic regression analysis demonstrated that GNB and Acute Physiology and Chronic Health Evaluation (APACHE) II score were independently associated with a CRP increase of 5 mg/dL from d-2 to d+1, and both were also independently associated with an increase of WCC levels from d(-2) to d(+1) of 5,000 x 10(3) cells/mm3. CONCLUSION: Increased levels of CRP and WCC are suggestive for GNB, while almost unchanged CRP and WCC levels are observed in patients with GPB. However, despite the different patterns observed, antimicrobial treatment as such cannot be guided based on both biomarkers. PMID- 17868443 TI - DetectiV: visualization, normalization and significance testing for pathogen detection microarray data. AB - DNA microarrays offer the possibility of testing for the presence of thousands of micro-organisms in a single experiment. However, there is a lack of reliable bioinformatics tools for the analysis of such data. We have developed DetectiV, a package for the statistical software R. DetectiV offers powerful yet simple visualization, normalization and significance testing tools. We show that DetectiV performs better than previously published software on a large, publicly available dataset. PMID- 17868442 TI - Invasive and noninvasive methods for studying pulmonary function in mice. AB - The widespread use of genetically altered mouse models of experimental asthma has stimulated the development of lung function techniques in vivo to characterize the functional results of genetic manipulations. Here, we describe various classical and recent methods of measuring airway responsiveness in vivo including both invasive methodologies in anesthetized, intubated mice (repetitive/non repetitive assessment of pulmonary resistance (RL) and dynamic compliance (Cdyn); measurement of low-frequency forced oscillations (LFOT)) and noninvasive technologies in conscious animals (head-out body plethysmography; barometric whole-body plethysmography). Outlined are the technical principles, validation and applications as well as the strengths and weaknesses of each methodology. Reviewed is the current set of invasive and noninvasive methods of measuring murine pulmonary function, with particular emphasis on practical considerations that should be considered when applying them for phenotyping in the laboratory mouse. PMID- 17868444 TI - Quitline referral vs. self-help manual for tobacco use cessation in the Emergency Department: a feasibility study. AB - BACKGROUND: Tobacco use counseling interventions delivered in the primary care setting are efficacious, but limited evidence exists regarding their feasibility or efficacy in the Emergency Department (ED). ED randomized controlled trials evaluating referral for outpatient tobacco use counseling have not had a single subject in the intervention groups attend scheduled clinic appointments. Telephone counseling potentially affords the opportunity to provide this population with individual counseling more conveniently than traditional clinic counseling. The purpose of this preliminary study was to evaluate the intervention completion rate among cigarette smokers enrolled through the ED in a tobacco quitline (QL) and to assess the feasibility of a randomized controlled trial assessing the efficacy of this intervention. METHODS: We conducted a prospective, randomized, controlled, un-blinded pilot study enrolling cigarette smokers presenting to a tertiary-care ED. Patients indicating a desire to quit smoking were randomized to receive either proactive telephone counseling through a QL (intervention) or a self-help manual (control). RESULTS: Of 212 smokers who indicated an interest in quitting, 20 subjects were randomized to the QL and 19 to control. Twenty-one did not meet inclusion criteria and 152 refused to participate. A total of 10 patients (50%) enrolled in the QL completed the full intervention. However, only a total of 20 patients (51%) were reached for follow up at 3 or 6 months (10 in each arm). At 6-month follow-up a total of six subjects had either disconnected their phone, no longer lived at the provided phone number or had provided an incorrect number. Two declined to provide follow up and the remainder could not be reached. Assuming all patients unavailable for follow-up were still smoking, the 7-day point prevalence smoking abstinence rate at 6 months was 20% (95% CI: 6 to 44%) for the QL group and 0% (95% CI: 0 to 15%) for the control group (p = 0.11). CONCLUSION: Compliance with the QL intervention was encouraging and may hold promise for providing needed tobacco use counseling to ED patients. Future studies are required, and should focus on more effective mechanisms to obtain outcome measures and a larger sample size. PMID- 17868445 TI - A Bayesian nonparametric method for prediction in EST analysis. AB - BACKGROUND: Expressed sequence tags (ESTs) analyses are a fundamental tool for gene identification in organisms. Given a preliminary EST sample from a certain library, several statistical prediction problems arise. In particular, it is of interest to estimate how many new genes can be detected in a future EST sample of given size and also to determine the gene discovery rate: these estimates represent the basis for deciding whether to proceed sequencing the library and, in case of a positive decision, a guideline for selecting the size of the new sample. Such information is also useful for establishing sequencing efficiency in experimental design and for measuring the degree of redundancy of an EST library. RESULTS: In this work we propose a Bayesian nonparametric approach for tackling statistical problems related to EST surveys. In particular, we provide estimates for: a) the coverage, defined as the proportion of unique genes in the library represented in the given sample of reads; b) the number of new unique genes to be observed in a future sample; c) the discovery rate of new genes as a function of the future sample size. The Bayesian nonparametric model we adopt conveys, in a statistically rigorous way, the available information into prediction. Our proposal has appealing properties over frequentist nonparametric methods, which become unstable when prediction is required for large future samples. EST libraries, previously studied with frequentist methods, are analyzed in detail. CONCLUSION: The Bayesian nonparametric approach we undertake yields valuable tools for gene capture and prediction in EST libraries. The estimators we obtain do not feature the kind of drawbacks associated with frequentist estimators and are reliable for any size of the additional sample. PMID- 17868446 TI - Long-term results of radiotherapy for periarthritis of the shoulder: a retrospective evaluation. AB - BACKGROUND: To evaluate retrospectively the results of radiotherapy for periarthritis of the shoulder METHODS: In 1983-2004, 141 patients were treated, all had attended at least one follow-up examination. 19% had had pain for several weeks, 66% for months and 14% for years. Shoulder motility was impaired in 137/140 patients. Nearly all patients had taken oral analgesics, 81% had undergone physiotherapy, five patients had been operated on, and six had been irradiated. Radiotherapy was applied using regular anterior-posterior opposing portals and Co-60 gamma rays or 4 MV photons. 89% of the patients received a total dose of 6 Gy (dose/fraction of 1 Gy twice weekly, the others had total doses ranging from 4 to 8 Gy. The patients and the referring doctors were given written questionnaires in order to obtain long-term results. The mean duration of follow-up was 6.9 years [0-20 years]. RESULTS: During the first follow-up examination at the end of radiotherapy 56% of the patients reported pain relief and improvement of motility. After in median 4.5 months the values were 69 and 89%, after 3.9 years 73% and 73%, respectively. There were virtually no side effects. In the questionnaires, 69% of the patients reported pain relief directly after radiotherapy, 31% up to 12 weeks after radiotherapy. 56% of the patients stated that pain relief had lasted for "years", in further 12% at least for "months". CONCLUSION: Low-dose radiotherapy for periarthropathy of the shoulder was highly effective and yielded long-lasting improvement of pain and motility without side effects. PMID- 17868447 TI - Effect of an herbal extract Number Ten (NT) on body weight in rats. AB - BACKGROUND: Chinese herbal extract Number Ten (NT) is a dietary herbal formulation prepared from rhubarb, ginger, astragalus, red sage and tumeric. This study tested the effectiveness of NT in reducing body weight gain in rats. METHODS: Sixty female Wistar rats were fed a high fat diet and acclimated to gavage feeding. The rats were divided into five treatment groups: (1) Control (n = 15); (2) NT-H (n = 15), 1.5 g/day; (3) NT-L (n = 10), 0.75 g/day; (4) Pr-fed (n = 10), pair fed to NT-H; (5) d-FF (n = 10), d-fenfluramine 2 mg/kg. Ten rats per group were sacrificed on day 56. Weight, food intake, clinical chemistry and body composition were evaluated. Five animals in the control and 1.5 g/day NT groups were left untreated during a two week recovery period. RESULTS: The 0.75 g/day NT, 1.5 g/day NT, d-fenfluramine and pair fed groups gained 24.6%, 33.3%, 12.3% and 33.3% less than the control respectively (P < 0.0006). Leptin decreased 27.5% to 46.2% in the treatment groups vs. control (P < 0.009). Parametrial fat decreased 14.1% to 55.5% in the NT and pair fed groups vs. control (P < 0.006). The NT groups had soft stools, loss of hair around the mouth and coloration to the urine and stool without evidence of blood or bilirubin (attributed to chromogens in NT). There were no differences between groups in the clinical chemistry. CONCLUSION: This study demonstrated the efficacy of NT in reducing weight gain in rodents. PMID- 17868448 TI - Inflammatory cytokines induce MAdCAM-1 in murine hepatic endothelial cells and mediate alpha-4 beta-7 integrin dependent lymphocyte endothelial adhesion in vitro. AB - BACKGROUND: MAdCAM-1 plays a central role in T-lymphocyte homing to the gut, but its role in chronic liver inflammation remains unknown. Therefore, this study measured MAdCAM-1 expression, regulation, and function in cultured murine hepatic endothelial cells. METHODS: Cultures of hepatic endothelial cells (HEC) were prepared from mice expressing a temperature-sensitive SV40 large T antigen (H-2Kb tsA58) under the control of an IFN-gamma promoter. Time and dose dependent expression of MAdCAM-1 in response to TNF-alpha, IL-1 beta and IFN-gamma was studied by immunoblotting. Lymphocyte adhesion was studied using alpha 4 beta 7 integrin expressing lymphocytes (TK-1) +/- anti-MAdCAM-1 mAb. RESULTS: TNF-alpha induced MAdCAM-1 dose-and time-dependently with maximum expression at 20 ng/ml and at 48 hours. IL-1 beta also induced MAdCAM-1 to a lesser extent compared to TNF-alpha; IFN-gamma did not induce MAdCAM-1. TNF-alpha significantly increased lymphocyte-endothelial adhesion (P < 0.01), which was reversed by anti-MAdCAM-1 antibody. MAdCAM-1 expression was also reduced by N-acetylcysteine and by two NO donors (SperNO, DETANO) suggesting that hepatic endothelial MAdCAM-1 is oxidant and NO regulated. CONCLUSION: MAdCAM-1 is a major determinant of leukocyte recruitment in chronic inflammation and is expressed by HEC in response to IL-1 beta and TNF-alpha. This system may provide a useful model for studying inflammatory mechanisms in liver disease and help determine if controlled MAdCAM 1 expression might influence inflammation in liver disease. PMID- 17868449 TI - Impact of image segmentation on high-content screening data quality for SK-BR-3 cells. AB - BACKGROUND: High content screening (HCS) is a powerful method for the exploration of cellular signalling and morphology that is rapidly being adopted in cancer research. HCS uses automated microscopy to collect images of cultured cells. The images are subjected to segmentation algorithms to identify cellular structures and quantitate their morphology, for hundreds to millions of individual cells. However, image analysis may be imperfect, especially for "HCS-unfriendly" cell lines whose morphology is not well handled by current image segmentation algorithms. We asked if segmentation errors were common for a clinically relevant cell line, if such errors had measurable effects on the data, and if HCS data could be improved by automated identification of well-segmented cells. RESULTS: Cases of poor cell body segmentation occurred frequently for the SK-BR-3 cell line. We trained classifiers to identify SK-BR-3 cells that were well segmented. On an independent test set created by human review of cell images, our optimal support-vector machine classifier identified well-segmented cells with 81% accuracy. The dose responses of morphological features were measurably different in well- and poorly-segmented populations. Elimination of the poorly-segmented cell population increased the purity of DNA content distributions, while appropriately retaining biological heterogeneity, and simultaneously increasing our ability to resolve specific morphological changes in perturbed cells. CONCLUSION: Image segmentation has a measurable impact on HCS data. The application of a multivariate shape-based filter to identify well-segmented cells improved HCS data quality for an HCS-unfriendly cell line, and could be a valuable post-processing step for some HCS datasets. PMID- 17868450 TI - Impact of intensive care on renal function before graft harvest: results of a monocentric study. AB - BACKGROUND: The aim of life-support measures in brain-dead donors is to preserve the functional value of their organs. In renal transplantation, serum creatinine level is one of the criteria for graft harvest. The aim of this study was to assess the impact of intensive care on donor renal function through two criteria: preharvesting serum creatinine level above 120 micromol/L and the elevation of serum creatinine level above 20% between intensive care unit (ICU) admission and graft harvest. METHODS: Between 1 January 1999 and 31 December 2005, we performed an observational study on 143 brain-dead donors. ICU chronology, hemodynamic, hematosis, and treatment data were collected for each patient from ICU admission to kidney removal. RESULTS: Twenty-two percent of the 143 patients had a serum creatinine level above 120 micromol/L before graft harvest. The independent factors revealed by multivariate analysis were the administration of epinephrine (odds ratio [OR]: 4.36, 95% confidence interval [CI]: 1.33 to 14.32; p = 0.015), oliguria (OR: 3.73, 95% CI: 1.22 to 11.36; p = 0.021), acidosis (OR: 3.26, 95% CI: 1.07 to 9.95; p = 0.038), the occurrence of disseminated intravascular coagulation (OR: 3.97, 95% CI: 1.05 to 15.02; p = 0.042), female gender (OR: 0.13, 95% CI: 0.03 to 0.50; p = 0.003), and the administration of desmopressin (OR: 0.12, 95% CI: 0.03 to 0.44; p = 0.002). The incidence of elevated serum creatinine level above 20% between admission and graft harvest was 41%. The independent risk factors were the duration of brain death greater than 24 hours (OR: 2.64, 95% CI: 1.25 to 5.59; p = 0.011) and the volume of mannitol (OR: 2.08, 95% CI: 1.03 to 4.21; p = 0.041). CONCLUSION: This study shows that the resuscitation of brain-dead donors impacts on their renal function. The uses of epinephrine and mannitol are associated with impairment of kidney function. It seems that graft harvest should be performed less than 24 hours after brain death diagnosis. PMID- 17868451 TI - Optical mapping as a routine tool for bacterial genome sequence finishing. AB - BACKGROUND: In sequencing the genomes of two Xenorhabdus species, we encountered a large number of sequence repeats and assembly anomalies that stalled finishing efforts. This included a stretch of about 12 Kb that is over 99.9% identical between the plasmid and chromosome of X. nematophila. RESULTS: Whole genome restriction maps of the sequenced strains were produced through optical mapping technology. These maps allowed rapid resolution of sequence assembly problems, permitted closing of the genome, and allowed correction of a large inversion in a genome assembly that we had considered finished. CONCLUSION: Our experience suggests that routine use of optical mapping in bacterial genome sequence finishing is warranted. When combined with data produced through 454 sequencing, an optical map can rapidly and inexpensively generate an ordered and oriented set of contigs to produce a nearly complete genome sequence assembly. PMID- 17868452 TI - Adjuvant therapeutic vaccination in patients with non-small cell lung cancer made lymphopenic and reconstituted with autologous PBMC: first clinical experience and evidence of an immune response. AB - BACKGROUND: Given the considerable toxicity and modest benefit of adjuvant chemotherapy for non-small cell lung cancer (NSCLC), there is clearly a need for new treatment modalities in the adjuvant setting. Active specific immunotherapy may represent such an option. However, clinical responses have been rare so far. Manipulating the host by inducing lymphopenia before vaccination resulted in a magnification of the immune response in the preclinical setting. To evaluate feasibility and safety of an irradiated, autologous tumor cell vaccine given following induction of lymphopenia by chemotherapy and reinfusion of autologous peripheral blood mononuclear cells (PBMC), we are currently conducting a pilot phase I clinical trial in patients with NSCLC following surgical resection. This paper reports on the first clinical experience and evidence of an immune response in patients suffering from NSCLC. METHODS: NSCLC patients stages I-IIIA are recruited. Vaccines are generated from their resected lung specimens. Patients undergo leukapheresis to harvest their PBMC prior to or following the surgical procedure. Furthermore, patients receive preparative chemotherapy (cyclophosphamide 350 mg/m2 and fludarabine 20 mg/m2 on 3 consecutive days) for induction of lymphopenia followed by reconstitution with their autologous PBMC. Vaccines are administered intradermally on day 1 following reconstitution and every two weeks for a total of up to five vaccinations. Granulocyte-macrophage colony-stimulating-factor (GM-CSF) is given continuously (at a rate of 50 microg/24 h) at the site of vaccination via minipump for six consecutive days after each vaccination. RESULTS: To date, vaccines were successfully manufactured for 4 of 4 patients. The most common toxicities were local injection-site reactions and mild constitutional symptoms. Immune responses to chemotherapy, reconstitution and vaccination are measured by vaccine site and delayed type hypersensitivity (DTH) skin reactions. One patient developed positive DTH skin tests so far. Immunohistochemical assessment of punch biopsies taken at the local vaccine site reaction revealed a dense lymphocyte infiltrate. Further immunohistochemical differentiation showed that CD1a+ cells had been attracted to the vaccine site as well as predominantly CD4+ lymphocytes. The 3-day combination chemotherapy consisting of cyclophosphamide and fludarabine induced a profound lymphopenia in all patients. Sequential FACS analysis revealed that different T cell subsets (CD4, CD8, CD4CD25) as well as granulocytes, B cells and NK cells were significantly reduced. Here, we report on clinical safety and feasibility of this vaccination approach during lymphoid recovery and demonstrate a patient example. CONCLUSION: Thus far, all vaccines were well tolerated. The overall trial design seems safe and feasible. Vaccine site reactions associated with infusion of GM-CSF via mini-pump are consistent with the postulated mechanism of action. More detailed immune-monitoring is required to evaluate a potential systemic immune response. Further studies to exploit homeostasis-driven T cell proliferation for the induction of a specific anti-tumor immune response in this clinical setting are warranted. PMID- 17868454 TI - The first organocatalytic carbonyl-ene reaction: isomerisation-free C-C bond formations catalysed by H-bonding thio-ureas. AB - Intramolecular carbonyl ene reactions of highly activated enophiles can be catalysed by H-bonding thio-ureas to give tertiary alcohols in high yields without extensive isomerisation side products. An asymmetric variant of this reaction was realised using a chiral thiourea but was limited by low enantioselectivity (up to 33% e.e.) and low turnover frequencies. PMID- 17868453 TI - Evolutionary conservation of P-selectin glycoprotein ligand-1 primary structure and function. AB - BACKGROUND: P-selectin glycoprotein ligand-1 (PSGL-1) plays a critical role in recruiting leukocytes in inflammatory lesions by mediating leukocyte rolling on selectins. Core-2 O-glycosylation of a N-terminal threonine and sulfation of at least one tyrosine residue of PSGL-1 are required for L- and P-selectin binding. Little information is available on the intra- and inter-species evolution of PSGL 1 primary structure. In addition, the evolutionary conservation of selectin binding site on PSGL-1 has not been previously examined in detail. Therefore, we performed multiple sequence alignment of PSGL-1 amino acid sequences of 14 mammals (human, chimpanzee, rhesus monkey, bovine, pig, rat, tree-shrew, bushbaby, mouse, bat, horse, cat, sheep and dog) and examined mammalian PSGL-1 interactions with human selectins. RESULTS: A signal peptide was predicted in each sequence and a propeptide cleavage site was found in 9/14 species. PSGL-1 N terminus is poorly conserved. However, each species exhibits at least one tyrosine sulfation site and, except in horse and dog, a T [D/E]PP [D/E] motif associated to the core-2 O-glycosylation of a N-terminal threonine. A mucin-like domain of 250-280 amino acids long was disclosed in all studied species. It lies between the conserved N-terminal O-glycosylated threonine (Thr-57 in human) and the transmembrane domain, and contains a central region exhibiting a variable number of decameric repeats (DR). Interspecies and intraspecies polymorphisms were observed. Transmembrane and cytoplasmic domain sequences are well conserved. The moesin binding residues that serve as adaptor between PSGL-1 and Syk, and are involved in regulating PSGL-1-dependent rolling on P-selectin are perfectly conserved in all analyzed mammalian sequences. Despite a poor conservation of PSGL-1 N-terminal sequence, CHO cells co-expressing human glycosyltransferases and human, bovine, pig or rat PSGL-1 efficiently rolled on human L- or P selectin. By contrast, pig or rat neutrophils were much less efficiently recruited than human or bovine neutrophils on human selectins. Horse PSGL-1, glycosylated by human or equine glycosyltransferases, did not interact with P selectin. In all five species, tyrosine sulfation of PSGL-1 was required for selectin binding. CONCLUSION: These observations show that PSGL-1 amino acid sequence of the transmembrane and cytoplasmic domains are well conserved and that, despite a poor conservation of PSGL-1 N-terminus, L- and P-selectin binding sites are evolutionary conserved. Functional assays reveal a critical role for post-translational modifications in regulating mammalian PSGL-1 interactions with selectins. PMID- 17868455 TI - Comparative acute efficacy and tolerability of OROS and immediate release formulations of methylphenidate in the treatment of adults with attention deficit/hyperactivity disorder. AB - BACKGROUND: The main aim of this study was to compare the safety and efficacy of IR MPH administered three times daily to those of once daily OROS-MPH. METHODS: Subjects were outpatient adults satisfying full diagnostic criteria for DSM-IV ADHD between 19 and 60 years of age. Data from two independently conducted 6-week placebo controlled, randomized clinical trials of IR-MPH (tid) and of OROS-MPH were pooled to create three study groups: Placebo (N = 116), IR-MPH (tid) (N = 102) and OROS-MPH (N = 67). RESULTS: Eight-five percent (N = 99) of placebo treated subjects, 77% (N = 79) of the IR-MPH (tid) treated subjects, and 82% (N = 55) of the OROS-MPH treated subjects completed the 6-week trial. Total daily doses at endpoint were 80.9 +/- 31.9 mg, 74.8 +/- 26.2 mg, and 95.4 +/- 26.3 mg in the OROS-MPH, IR-MPH (tid), and placebo groups, respectively. At endpoint, 66% (N = 44) of subjects receiving OROS-MPH and 70% (N = 71) of subjects receiving IR MPH (tid) were considered responders compared with 31% (N = 36) on placebo. CONCLUSION: Comparison of data from two similarly designed, large, randomized, placebo-controlled, trials, showed that equipotent daily doses of once daily OROS MPH had similar efficacy to that of TID administered IR MPH. PMID- 17868456 TI - HAP1 can sequester a subset of TBP in cytoplasmic inclusions via specific interaction with the conserved TBP(CORE). AB - BACKGROUND: Huntington's disease, spinal and bulbar muscular atrophy, and spinocerebellar ataxia 17 (SCA17) are caused by expansions in the polyglutamine (polyQ) repeats in Huntingtin protein (Htt), androgen receptor protein (AR), and TATA-binding protein (TBP), respectively. Htt-associated protein 1 (HAP1), a component of neuronal cytoplasmic stigmoid bodies (STBs), can sequester polyQ expanded Htt and AR in STBs, thereby antagonizing formation of the nuclear aggregates associated with apoptotic neuron loss and disease progression. RESULTS: Clones of HAP1 were isolated from unbiased two-hybrid screens for proteins that interact with TBP. Domain mapping showed that regions between amino acids 157 and 261 and between amino acids 473 and 582 of mouse HAP1 both bind specifically to the conserved C-terminal TBP(CORE) domain, away from the TBP N terminal polyQ region. When fluorescently tagged versions of HAP1 or TBP were expressed independently in COS-7, 293, or Neuro-2a cells, all TBP localized to the nucleus and all HAP1 assembled into cytoplasmic stigmoid-like bodies (STLBs). When co-expressed, a portion of the TBP was assembled into the HAP1 STLBs while the remainder was localized to the nucleus. Although the TBP N terminus, including the polyQ region, was unnecessary for TBP-HAP1 interaction, in mammalian cells, removal of the TBP Q(repeat) reduced the proportion of TBP that assembled into STLBs, whereas expansion of the Q(repeat) had no significant affect on TBP subcellular localization. CONCLUSION: HAP1 can sequester a subset of TBP protein away from the nucleus; extranuclear TBP sequestration is quantitatively influenced by the TBP polyQ repeat. These results suggest HAP1 could provide protection from SCA17 neuropathology. PMID- 17868457 TI - Kaposi's sarcoma associated herpesvirus G-protein coupled receptor activation of cyclooxygenase-2 in vascular endothelial cells. AB - BACKGROUND: Kaposi's sarcoma associated herpesvirus (KSHV) is the etiologic agent of Kaposi's sarcoma (KS), a highly vascularized neoplasm characterized by endothelial-derived spindle-shaped tumor cells. KSHV-infected microvascular endothelial cells demonstrate increased cyclooxygenase-2 (COX-2) expression and KS lesions have high levels of prostaglandin E2 (PGE2), a short-lived eicosanoid dependent on cyclooxygenase activity that has been linked to pathogenesis of other neoplasias. To determine whether increased COX-2 expression and PGE2 production is mediated by the angiogenic and tumorigenic KSHV-encoded G-protein coupled receptor (vGPCR), we developed a recombinant retrovirus to express vGPCR in Human Umbilical Vascular Endothelial Cells (HUVEC). RESULTS: In the present study, we show that vGPCR-expressing HUVEC exhibit a spindle-like morphology that is characteristic of KS endothelial cells and demonstrate selective induction of PGE2 and COX-2. By treating vGPCR-expressing HUVEC with selective and non selective COX inhibitors, we show that vGPCR-induced PGE2 production is dependent on the expression of COX-2 but not COX-1. CONCLUSION: Taken together, these results demonstrate that vGPCR induces expression of COX-2 and PGE2 that may mediate the paracrine effects of this key viral protein in KS pathogenesis. PMID- 17868459 TI - The effect of growth on the correlation between the spinal and rib cage deformity: implications on idiopathic scoliosis pathogenesis. AB - BACKGROUND: Numerous studies have attempted to quantify the correlation between the surface deformity and the Cobb angle without considering growth as an important factor that may influence this correlation. In our series, we noticed that in some younger referred children from the school-screening program there is a discrepancy between the thoracic scoliometer readings and the morphology of their spine. Namely there is a rib hump but no spinal curve and consequently no Cobb angle reading in radiographs, discrepancy which fades away in older children. Based on this observation, we hypothesized that in scoliotics the correlation between the rib cage deformity and this of the spine is weak in younger children and vice versa. METHODS: Eighty three girls referred on the basis of their hump reading on the scoliometer, with a mean age of 13.4 years old (range 7-18), were included in the study. The spinal deformity was assessed by measuring the thoracic Cobb angle from the postero-anterior spinal radiographs. The rib cage deformity was quantified by measuring the rib-index at the apex of the thoracic curve from the lateral spinal radiographs. The rib-index is defined as the ratio between the distance of the posterior margin of the vertebral body and the most extended point of the most projecting rib contour, divided by the distance between the posterior margin of the same vertebral body and the most protruding point of the least projecting rib contour. Statistical analysis included linear regression models with and without the effect of the variable age. We divided our sample in two subgroups, namely the younger (7-13 years old) and the older (14-18 years old) than the mean age participants. A univariate linear regression analysis was performed for each age group in order to assess the effect of age on Cobb angle and rib index correlation. RESULTS: Twenty five per cent of patients with an ATI more than or equal 7 degrees had a spinal curve under 10 degrees or had a straight spine. Linear regressions between the dependent variable "Thoracic Cobb angle" with the independent variable "rib index" without the effect of the variable "age" is not statistical significant. After sample split, the linear relationship is statistically significant in the age group 14-18 years old (p < 0.03). CONCLUSION: Growth has a significant effect in the correlation between the thoracic and the spinal deformity in girls with idiopathic scoliosis. Therefore it should be taken into consideration when trying to assess the spinal deformity from surface measurements. The findings of the present study implicate the role of the thorax, as it shows that the rib cage deformity precedes the spinal deformity in the pathogenesis of idiopathic scoliosis. PMID- 17868458 TI - Characterization of heterotypic interaction effects in vitro to deconvolute global gene expression profiles in cancer. AB - BACKGROUND: Perturbations in cell-cell interactions are a key feature of cancer. However, little is known about the systematic effects of cell-cell interaction on global gene expression in cancer. RESULTS: We used an ex vivo model to simulate tumor-stroma interaction by systematically co-cultivating breast cancer cells with stromal fibroblasts and determined associated gene expression changes with cDNA microarrays. In the complex picture of epithelial-mesenchymal interaction effects, a prominent characteristic was an induction of interferon-response genes (IRGs) in a subset of cancer cells. In close proximity to these cancer cells, the fibroblasts secreted type I interferons, which, in turn, induced expression of the IRGs in the tumor cells. Paralleling this model, immunohistochemical analysis of human breast cancer tissues showed that STAT1, the key transcriptional activator of the IRGs, and itself an IRG, was expressed in a subset of the cancers, with a striking pattern of elevated expression in the cancer cells in close proximity to the stroma. In vivo, expression of the IRGs was remarkably coherent, providing a basis for segregation of 295 early-stage breast cancers into two groups. Tumors with high compared to low expression levels of IRGs were associated with significantly shorter overall survival; 59% versus 80% at 10 years (log-rank p = 0.001). CONCLUSION: In an effort to deconvolute global gene expression profiles of breast cancer by systematic characterization of heterotypic interaction effects in vitro, we found that an interaction between some breast cancer cells and stromal fibroblasts can induce an interferon response, and that this response may be associated with a greater propensity for tumor progression. PMID- 17868460 TI - Cable properties and propagation velocity in a long single chain of simulated myocardial cells. AB - BACKGROUND: Propagation of simulated action potentials (APs) was previously studied in short single chains and in two-dimensional sheets of myocardial cells 123. The present study was undertaken to examine propagation in a long single chain of cells of various lengths, and with varying numbers of gap-junction (g-j) channels, and to compare propagation velocity with the cable properties such as the length constant (lambda). METHODS AND RESULTS: Simulations were carried out using the PSpice program as previously described. When the electric field (EF) mechanism was dominant (0, 1, and 10 gj-channels), the longer the chain length, the faster the overall velocity (theta(ov)). There seems to be no simple explanation for this phenomenon. In contrast, when the local-circuit current mechanism was dominant (100 gj-channels or more), theta(ov) was slightly slowed with lengthening of the chain. Increasing the number of gj-channels produced an increase in theta(ov) and caused the firing order to become more uniform. The end effect was more pronounced at longer chain lengths and at greater number of gj channels. When there were no or only few gj-channels (namely, 0, 10, or 30), the voltage change (DeltaV(m)) in the two contiguous cells (#50 & #52) to the cell injected with current (#51) was nearly zero, i.e., there was a sharp discontinuity in voltage between the adjacent cells. When there were many gj channels (e.g., 300, 1000, 3000), there was an exponential decay of voltage on either side of the injected cell, with the length constant (lambda) increasing at higher numbers of gj-channels. The effect of increasing the number of gj-channels on increasing lambda was relatively small compared to the larger effect on theta(ov). theta(ov) became very non-physiological at 300 gj-channels or higher. CONCLUSION: Thus, when there were only 0, 1, or 10 gj-channels, theta(ov) increased with increase in chain length, whereas at 100 gj-channels or higher, theta(ov) did not increase with chain length. When there were only 0, 10, or 30 gj-channels, there was a very sharp decrease in DeltaV(m) in the two contiguous cells on either side of the injected cell, whereas at 300, 1000, or 3000 gj channels, the voltage decay was exponential along the length of the chain. The effect of increasing the number of gj-channels on spread of current was relatively small compared to the large effect on theta(ov). PMID- 17868461 TI - Inverse association of plasma IL-13 and inflammatory chemokines with lung function impairment in stable COPD: a cross-sectional cohort study. AB - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous syndrome characterized by varying degrees of airflow limitation and diffusion impairment. There is increasing evidence to suggest that COPD is also characterized by systemic inflammation. The primary goal of this study was to identify soluble proteins in plasma that associate with the severity of airflow limitation in a COPD cohort with stable disease. A secondary goal was to assess whether unique markers associate with diffusion impairment, based on diffusion capacity of carbon monoxide (DLCO), independent of the forced expiratory volume in 1 second (FEV1). METHODS: A cross sectional study of 73 COPD subjects was performed in order to examine the association of 25 different plasma proteins with the severity of lung function impairment, as defined by the baseline measurements of the % predicted FEV1 and the % predicted DLCO. Plasma protein concentrations were assayed using multiplexed immunobead-based cytokine profiling. Associations between lung function and protein concentrations were adjusted for age, gender, pack years smoking history, current smoking, inhaled corticosteroid use, systemic corticosteroid use and statin use. RESULTS: Plasma concentrations of CCL2/monocyte chemoattractant protein-1 (CCL2/MCP-1), CCL4/macrophage inflammatory protein-1 beta (CCL4/MIP-1 beta), CCL11/eotaxin, and interleukin-13 (IL-13) were inversely associated with the % FEV1. Plasma concentrations of soluble Fas were associated with the % DLCO, whereas CXCL9/monokine induced by interferon-gamma (CXCL9/Mig), granulocyte- colony stimulating factor (G-CSF) and IL-13 showed inverse relationships with the % DLCO. CONCLUSION: Systemic inflammation in a COPD cohort is characterized by cytokines implicated in inflammatory cell recruitment and airway remodeling. Plasma concentrations of IL-13 and chemoattractants for monocytes, T lymphocytes, and eosinophils show associations with increasing severity of disease. Soluble Fas, G-CSF and CXCL9/Mig may be unique markers that associate with disease characterized by disproportionate abnormalities in DLCO independent of the FEV1. PMID- 17868462 TI - Brief Intervention in Type 1 diabetes - Education for Self-efficacy (BITES): Protocol for a randomised control trial to assess biophysical and psychological effectiveness. AB - BACKGROUND: Self management is the cornerstone of effective preventive care in diabetes. Educational interventions that provide self-management skills for people with diabetes have been shown to reduce blood glucose concentrations. This in turn has the potential to reduce rates of complications. However, evidence to support type, quantity, setting and mode of delivery of self-management education is sparse. OBJECTIVES: To study the biophysical and psychological effectiveness of a brief psycho-educational intervention for type 1 diabetes in adults. METHODS/DESIGN: DESIGN: Randomised controlled clinical trial. SETTING: Multidisciplinary specialist diabetes centre. HYPOTHESIS: Our hypothesis was that the brief (2.5-day) intervention would be biophysically and psychologically effective for people with type 1 diabetes. INTERVENTION: A brief psycho educational intervention for type 1 diabetes developed by a multi-professional team comprising of a consultant diabetologist, a diabetes specialist nurse, a specialist diabetes dietician and a clinical health psychologist and delivered in 20 hours over 2.5 days. PRIMARY OUTCOMES: HbA1c and severe hypoglycaemia. SECONDARY OUTCOMES: Blood pressure, weight, height, lipid profile and composite psychometric scales. PARTICIPANTS: We shall consent and recruit 120 subjects with postal invitations sent to eligible participants. Volunteers are to be seen at randomisation clinics where independent researcher verify eligibility and obtain consent. We shall randomise 60 to BITES and 60 to standard care. ELIGIBILITY CRITERIA: Type 1 diabetes for longer than 12 months, multiple injection therapy for at least two months, minimum age of 18 and ability to read and write.Randomisation: An independent evaluator to block randomise (block-size = 6), to intervention or control groups using sealed envelopes in strict ascendant order. Control group will receive standard care. ASSESSMENT: PARTICIPANTS in both groups would attend unblinded assessments at baseline, 3, 6 and 12 months, in addition to their usual care. After the intervention, usual care would be provided.Ethics approval: York Research Ethics Committee (Ref: 01/08/016) approved the study protocol. DISCUSSION: We hope the trial will demonstrate feasibility of a pragmatic randomised trial of BITES and help quantify therapeutic effect. A follow up multi-centre trial powered to detect this effect could provide further evidence. TRIAL REGISTRATION: Current Controlled Trials ISRCTN75807800. PMID- 17868463 TI - ChIP on SNP-chip for genome-wide analysis of human histone H4 hyperacetylation. AB - BACKGROUND: SNP microarrays are designed to genotype Single Nucleotide Polymorphisms (SNPs). These microarrays report hybridization of DNA fragments and therefore can be used for the purpose of detecting genomic fragments. RESULTS: Here, we demonstrate that a SNP microarray can be effectively used in this way to perform chromatin immunoprecipitation (ChIP) on chip as an alternative to tiling microarrays. We illustrate this novel application by mapping whole genome histone H4 hyperacetylation in human myoblasts and myotubes. We detect clusters of hyperacetylated histone H4, often spanning across up to 300 kilobases of genomic sequence. Using complementary genome-wide analyses of gene expression by DNA microarray we demonstrate that these clusters of hyperacetylated histone H4 tend to be associated with expressed genes. CONCLUSION: The use of a SNP array for a ChIP-on-chip application (ChIP on SNP-chip) will be of great value to laboratories whose interest is the determination of general rules regarding the relationship of specific chromatin modifications to transcriptional status throughout the genome and to examine the asymmetric modification of chromatin at heterozygous loci. PMID- 17868464 TI - InSite: a computational method for identifying protein-protein interaction binding sites on a proteome-wide scale. AB - We propose InSite, a computational method that integrates high-throughput protein and sequence data to infer the specific binding regions of interacting protein pairs. We compared our predictions with binding sites in Protein Data Bank and found significantly more binding events occur at sites we predicted. Several regions containing disease-causing mutations or cancer polymorphisms in human are predicted to be binding for protein pairs related to the disease, which suggests novel mechanistic hypotheses for several diseases. PMID- 17868466 TI - Xiphodynia: a diagnostic conundrum. AB - This paper presents 3 case reports of xiphodynia that presented to a chiropractic clinic. The paper examines aspects of xiphodynia including relevant anatomy of the xiphoid, as well as the incidence, aetiology, symptoms, diagnosis, and treatment. A brief overview of the mechanism of referred pain is presented. PMID- 17868465 TI - Measurement error adjustment in essential fatty acid intake from a food frequency questionnaire: alternative approaches and methods. AB - BACKGROUND: We aimed at assessing the degree of measurement error in essential fatty acid intakes from a food frequency questionnaire and the impact of correcting for such an error on precision and bias of odds ratios in logistic models. To assess these impacts, and for illustrative purposes, alternative approaches and methods were used with the binary outcome of cognitive decline in verbal fluency. METHODS: Using the Atherosclerosis Risk in Communities (ARIC) study, we conducted a sensitivity analysis. The error-prone exposure - visit 1 fatty acid intake (1987-89) - was available for 7,814 subjects 50 years or older at baseline with complete data on cognitive decline between visits 2 (1990-92) and 4 (1996-98). Our binary outcome of interest was clinically significant decline in verbal fluency. Point estimates and 95% confidence intervals were compared between naive and measurement-error adjusted odds ratios of decline with every SD increase in fatty acid intake as % of energy. Two approaches were explored for adjustment: (A) External validation against biomarkers (plasma fatty acids in cholesteryl esters and phospholipids) and (B) Internal repeat measurements at visits 2 and 3. The main difference between the two is that Approach B makes a stronger assumption regarding lack of error correlations in the structural model. Additionally, we compared results from regression calibration (RCAL) to those from simulation extrapolation (SIMEX). Finally, using structural equations modeling, we estimated attenuation factors associated with each dietary exposure to assess degree of measurement error in a bivariate scenario for regression calibration of logistic regression model. RESULTS AND CONCLUSION: Attenuation factors for Approach A were smaller than B, suggesting a larger amount of measurement error in the dietary exposure. Replicate measures (Approach B) unlike concentration biomarkers (Approach A) may lead to imprecise odds ratios due to larger standard errors. Using SIMEX rather than RCAL models tends to preserve precision of odds ratios. We found in many cases that bias in naive odds ratios was towards the null. RCAL tended to correct for a larger amount of effect bias than SIMEX, particularly for Approach A. PMID- 17868467 TI - Comparison of three molecular methods for the detection and speciation of Plasmodium vivax and Plasmodium falciparum. AB - BACKGROUND: Accurate diagnosis of Plasmodium spp. is essential for the rational treatment of malaria. Despite its many disadvantages, microscopic examination of blood smears remains the current "gold standard" for malaria detection and speciation. PCR assays offer an alternative to microscopy which has been shown to have superior sensitivity and specificity. Unfortunately few comparative studies have been done on the various molecular based speciation methods. METHODS: The sensitivity, specificity and cost effectiveness of three molecular techniques were compared for the detection and speciation of Plasmodium falciparum and Plasmodium vivax from dried blood spots collected from 136 patients in western Thailand. The results from the three molecular speciation techniques (nested PCR, multiplex PCR, and real-time PCR) were used to develop a molecular consensus (two or more identical PCR results) as an alternative gold standard. RESULTS: According to the molecular consensus, 9.6% (13/136) of microscopic diagnoses yielded false negative results. Multiplex PCR failed to detect P. vivax in three mixed isolates, and the nested PCR gave a false positive P. falciparum result in one case. Although the real-time PCR melting curve analysis was the most expensive method, it was 100% sensitive and specific and least time consuming of the three molecular techniques investigated. CONCLUSION: Although microscopy remains the most appropriate method for clinical diagnosis in a field setting, its use as a gold standard may result in apparent false positive results by superior techniques. Future studies should consider using more than one established molecular methods as a new gold standard to assess novel malaria diagnostic kits and PCR assays. PMID- 17868468 TI - Adaptive expression responses in the Pol-gamma null strain of S. pombe depleted of mitochondrial genome. AB - BACKGROUND: DNA polymerase gamma(Pol-gamma) has been shown to be essential for maintenance of the mitochondrial genome (mtDNA) in the petite-positive budding yeast Saccharomyces cerevisiae. Budding yeast cells lacking mitochondria exhibit a slow-growing or petite-colony phenotype. Petite strains fail to grow on non fermentable carbon sources. However, it is not clear whether the Pol-gamma is required for mtDNA maintenance in the petite-negative fission yeast Schizosaccharomyces pombe. RESULTS: We show that disruption of the nuclear gene pog1+ that encodes Pol-gamma is sufficient to deplete mtDNA in S. pombe. Cells bearing pog1Delta allele require substantial growth periods to form petite colonies. Mitotracker assays indicate that pog1Delta cells are defective in mitochondrial function and EM analyses suggest that pog1Delta cells lack normal mitochondrial structures. Depletion of mtDNA in pog1Delta cells is evident from quantitative real-time PCR assays. Genome-wide expression profiles of pog1Delta and other mtDNA-less cells reveal that many genes involved in response to stimulus, energy derivation by oxidation of organic compounds, cellular carbohydrate metabolism, and energy reserve metabolism are induced. Conversely, many genes encoding proteins involved in amino acid metabolism and oxidative phosphorylation are repressed. CONCLUSION: By showing that Pol-gamma is essential for mtDNA maintenance and disruption of pog1+ alters the genome-wide expression profiles, we demonstrated that cells lacking mtDNA exhibit adaptive nuclear gene expression responses in the petite-negative S. pombe. PMID- 17868469 TI - The nicotinic acetylcholine receptor gene family of the silkworm, Bombyx mori. AB - BACKGROUND: Nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic cholinergic transmission in the insect central nervous system. The insect nAChR is the molecular target of a class of insecticides, neonicotinoids. Like mammalian nAChRs, insect nAChRs are considered to be made up of five subunits, coded by homologous genes belonging to the same family. The nAChR subunit genes of Drosophila melanogaster, Apis mellifera and Anopheles gambiae have been cloned previously based on their genome sequences. The silkworm Bombyx mori is a model insect of Lepidoptera, among which are many agricultural pests. Identification and characterization of B. mori nAChR genes could provide valuable basic information for this important family of receptor genes and for the study of the molecular mechanisms of neonicotinoid action and resistance. RESULTS: We searched the genome sequence database of B. mori with the fruit fly and honeybee nAChRs by tBlastn and cloned all putative silkworm nAChR cDNAs by reverse transcriptase polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE) methods. B. mori appears to have the largest known insect nAChR gene family to date, including nine alpha-type subunits and three beta-type subunits. The silkworm possesses three genes having low identity with others, including one alpha and two beta subunits, alpha 9, beta2 and beta 3. Like the fruit fly and honeybee counterparts, silkworm nAChR gene alpha 6 has RNA-editing sites, and alpha 4, alpha 6 and alpha 8 undergo alternative splicing. In particular, alternative exon 7 of Bm alpha 8 may have arisen from a recent duplication event. Truncated transcripts were found for Bm alpha 4 and Bm alpha 5. CONCLUSION: B. mori possesses a largest known insect nAChR gene family characterized to date, including nine alpha-type subunits and three beta-type subunits. RNA-editing, alternative splicing and truncated transcripts were found in several subunit genes, which might enhance the diversity of the gene family. PMID- 17868470 TI - Do bullae and emphysema increase risk of pneumothorax in silicosis? AB - BACKGROUND: The occurrence of occupational lung diseases is decreasing due to improvements in occupational health in recent years; however, silicosis and its complications remain important occupational health problems. We have studied the role of emphysema and bullae as predictive factors of secondary spontaneous pneumothorax in acute and accelerated silicosis. METHODS: This study was carried out using questionnaire items on occupational history and conventional computed tomography of lungs. Differences between two groups (silicosis with and without secondary spontaneous pneumothorax) in terms of age, interval of exposure diagnosis and therefore silica exposure duration were assessed by independent t test. Fisher's exact test was used to determine the association between secondary spontaneous pneumothorax and both emphysema and bullae. RESULTS: We found a significant association between secondary spontaneous pneumothorax and bullae in acute and accelerated silicosis. CONCLUSION: Pneumothorax in silicosis could be attributed to previous bullae. PMID- 17868471 TI - Ensuring sustained ACT production and reliable artemisinin supply. AB - INTRODUCTION: This paper reviews recent trends in the production, supply and price of the active ingredients as well as finished ACT products. Production and cost data provided in this paper are based on an ongoing project (Artepal). Stability data are derived from a development project on rectal artesunate. DISCUSSION: The artemisinin raw material and its derivatives appear to be very stable compared to the finished products. Supply of artemisinin changed in May 2004 when the Global Fund shifted financial support to qualified countries from chloroquine or sulphadoxine-pyrimethamine to an ACT for treatment of malaria. First, there was a sudden shortage of the starting material, and short term scarcity led to a steep rise in API price: it increased dramatically in 2004, from $350 per kg to more than $1000. Second, there was a parallel increase in the number of companies extracting artemisinin from 10 to 80 between 2003 and 2005 in China, and from 3 to 20 in Vietnam. Commercial cultivation began also in East Africa and Madagascar.A steady and predictable demand for the crop can eliminate such wide fluctuations and indirectly contribute to price stability of the herb, the API and ACT. With appropriate mechanisms to reduce those fluctuations, the cost of artemisinin might decrease sustainably to US$ 250-300 per kg. CONCLUSION: Today the global health community is facing the risk of another cyclical swing with lower demand feeding into reduced planting of A. annua and, thereafter, a new shortage of the raw material and higher API prices. International donors, the largest purchasers for ACTs could better coordinate their activities, in order to guarantee purchase of ACTs and consequently of API with manufacturers. In parallel, the base of quality producers of APIs and finished ACT products needs to be broadened.While the ACT programme is still in its early stages, the consequences of another wave of artemisinin and ACT shortages would permanently discredit it and impede any progress in rolling malaria back. PMID- 17868472 TI - Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study. AB - BACKGROUND: Currently there is no effective treatment available to retard cyst growth and to prevent the progression to end-stage renal failure in patients with autosomal dominant polycystic kidney disease (ADPKD). Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus) markedly slows cyst development and renal functional deterioration. Based on these promising results in animals we have designed and initiated the first randomized controlled trial (RCT) to examine the effectiveness, safety and tolerability of sirolimus to retard disease progression in ADPKD. METHOD/DESIGN: This single center, randomised controlled, open label trial assesses the therapeutic effect, safety and tolerability of the mTOR inhibitor sirolimus (Rapamune) in patients with autosomal dominant polycystic kidney disease and preserved renal function. The primary outcome will be the inhibition of kidney volume growth measured by magnetic resonance imaging (MRI) volumetry. Secondary outcome parameters will be preservation of renal function, safety and tolerability of sirolimus. DISCUSSION: The results from this proof-of-concept RCT will for the first time show whether treatment with sirolimus effectively retards cyst growth in patients with ADPKD. PMID- 17868473 TI - Galapagos and Californian sea lions are separate species: Genetic analysis of the genus Zalophus and its implications for conservation management. AB - BACKGROUND: Accurate formal taxonomic designations are thought to be of critical importance for the conservation of endangered taxa. The Galapagos sea lion (GSL), being appreciated as a key element of the Galapagos marine ecosystem, has lately been listed as 'vulnerable' by the IUCN. To date there is, however, hardly any scientific evidence, whether it constitutes a separate entity from its abundant Californian neighbour (CSL). In this paper, we delineate the taxonomic relationships within the genus Zalophus being comprised of the Galapagos sea lion, the Californian sea lion and the already extinct Japanese sea lion (JSL). RESULTS: Using a set of different phylogenetic reconstruction approaches, we find support for monophyly of all three taxa without evidence of reticulation events. Molecular clock estimates place time to common ancestry of the Galapagos sea lion and the Californian sea lion at about 2.3 +/- 0.5 mya. Genetic separation is further suggested by diagnostic SNPs in the mitochondrial and nuclear genome. Microsatellite markers confirm this trend, showing numerous private alleles at most of the 25 investigated loci. Microsatellite-based estimates of genetic differentiation between the Galapagos sea lion and the Californian sea lion indicate significant genetic differentiation. Gene diversity is 14% lower in the Galapagos sea lion than in the Californian sea lion, but there is no evidence for recent bottleneck events in the Galapagos sea lion. CONCLUSION: Based on molecular evidence we build a case for classifying the Galapagos sea lion (Zalophus wollebaeki), the Californian sea lion (Zalophus californianus) and the Japanese sea lion (Zalophus japonicus) as true species. As morphological characters do not necessarily fully reflect the rapid divergence on the molecular level, the study can be considered as a test case for deriving species status from molecular evidence. We further use the results to discuss the role of genetics in conservation policy for an organism that already is under the general protection of the habitat it lives in. PMID- 17868474 TI - Enterococcal colonization of infants in a neonatal intensive care unit: associated predictors, risk factors and seasonal patterns. AB - BACKGROUND: During and shortly after birth, newborn infants are colonized with enterococci. This study analyzes predictors for early enterococcal colonization of infants in a neonatal intensive care unit and describes risk factors associated with multidrugresistant enterococci colonization and its seasonal patterns. METHODS: Over a 12-month period, we performed a prospective epidemiological study in 274 infants admitted to a neonatal intensive care unit. On the first day of life, we compared infants with enterococcal isolates detected in meconium or body cultures to those without. We then tested the association of enterococcal colonization with peripartal predictors/risk factors by using bivariate and multivariate statistical methods. RESULTS: Twenty-three percent of the infants were colonized with enterococci. The three most common enterococcal species were E. faecium (48% of isolates), E. casseliflavus (25%) and E. faecalis (13%). Fifty-seven percent of the enterococci found were resistant to three of five antibiotic classes, but no vancomycin-resistant isolates were observed. During winter/spring months, the number of enterococci and multidrug-resistant enterococci were higher than in summer/fall months (p = 0.002 and p < 0.0001, respectively). With respect to enterococcal colonization on the first day of life, predictors were prematurity (p = 0.043) and low birth weight (p = 0.011). With respect to colonization with multidrug-resistant enterococci, risk factors were prematurity (p = 0.0006), low birth weight (p < 0.0001) and prepartal antibiotic treatment (p = 0.019). Using logistic regression, we determined that gestational age was the only parameter significantly correlated with multidrug resistant enterococci colonization. No infection with enterococci or multidrugresistant enterococci in the infants was detected. The outcome of infants with and without enterococcal colonization was the same with respect to death, necrotizing enterocolitis, intracerebral hemorrhage and bronchopulmonary dysplasia. CONCLUSION: In neonatal intensive care units, an infant's susceptibility to early colonization with enterococci in general, and his or her risk for colonization with multidrug-resistant enterococci in particular, is increased in preterm newborns, especially during the winter/spring months. The prepartal use of antibiotics with no known activity against enterococci appears to increase the risk for colonization with multidrug-resistant enterococci. PMID- 17868475 TI - Do general practitioners adhere to the guideline on infectious conjunctivitis? Results of the Second Dutch National Survey of General Practice. AB - BACKGROUND: In 1996 the guideline 'The Red Eye' was first published by the Dutch College of General Practitioners. The extent to which general practitioners adhere to this guideline is unclear. Recently, data on the management of infectious conjunctivitis by general practitioners became available from the Second Dutch National Survey of General Practice. We measured the age-specific incidence of infectious conjunctivitis, described its management by Dutch general practitioners, and then compared these findings with the recommendations made in the guideline. METHODS: In 2001, over a 12-month period, data from all patient contacts with 195 general practitioners were taken from electronic medical records. Registration was episode-oriented; all consultations dealing with the same health problem were grouped into disease episodes. Data concerning all episodes of infectious conjunctivitis (ICPC-code F70 and sub codes) were analysed. RESULTS: Over one year, 5,213 new and recurrent episodes of infectious conjunctivitis were presented to general practitioners from a population of N = 375,899, resulting in an overall incidence rate of 13.9 per 1000 person-years, varying from more than 80/1000 py in children up to one-year old, to less than 12/1000 py in children over the age of 4. Topical ophthalmic ointments were prescribed in 87% of the episodes, of which 80% was antibiotic treatment. Fusidic acid gel was most frequently prescribed (69%). In most episodes general practitioners did not adhere to the guideline. CONCLUSION: In 2001, the management of infectious conjunctivitis by Dutch general practitioners was not in accordance with the recommendations of the consensus-based guideline published five years previously, despite its wide distribution. In 2006 this guideline was revised. Its successful implementation requires more than distribution alone. Probably the most effective way to achieve this is by following a model for systemic implementation. PMID- 17868476 TI - Calcium-sensitive regulation of monoamine oxidase-A contributes to the production of peroxyradicals in hippocampal cultures: implications for Alzheimer disease related pathology. AB - BACKGROUND: Calcium (Ca2+) has recently been shown to selectively increase the activity of monoamine oxidase-A (MAO-A), a mitochondria-bound enzyme that generates peroxyradicals as a natural by-product of the deamination of neurotransmitters such as serotonin. It has also been suggested that increased intracellular free Ca2+ levels as well as MAO-A may be contributing to the oxidative stress associated with Alzheimer disease (AD). RESULTS: Incubation with Ca2+ selectively increases MAO-A enzymatic activity in protein extracts from mouse hippocampal HT-22 cell cultures. Treatment of HT-22 cultures with the Ca2+ ionophore A23187 also increases MAO-A activity, whereas overexpression of calbindin-D28K (CB-28K), a Ca2+-binding protein in brain that is greatly reduced in AD, decreases MAO-A activity. The effects of A23187 and CB-28K are both independent of any change in MAO-A protein or gene expression. The toxicity (via production of peroxyradicals and/or chromatin condensation) associated with either A23187 or the AD-related beta-amyloid peptide, which also increases free intracellular Ca2+, is attenuated by MAO-A inhibition in HT-22 cells as well as in primary hippocampal cultures. CONCLUSION: These data suggest that increases in intracellular Ca2+ availability could contribute to a MAO-A-mediated mechanism with a role in AD-related oxidative stress. PMID- 17868477 TI - Clinical utility of the Mood and Anxiety Symptom Questionnaire (MASQ) in a sample of young help-seekers. AB - BACKGROUND: The overlap between Depression and Anxiety has led some researchers to conclude that they are manifestations of a broad, non-specific neurotic disorder. However, others believe that they can be distinguished despite sharing symptoms of general distress. The Tripartite Model of Affect proposes an anxiety specific, a depression-specific and a shared symptoms factor. Watson and Clark developed the Mood and Anxiety Symptom Questionnaire (MASQ) to specifically measure these Tripartite constructs. Early research showed that the MASQ distinguished between dimensions of Depression and Anxiety in non-clinical samples. However, two recent studies have cautioned that the MASQ may show limited validity in clinical populations. The present study investigated the clinical utility of the MASQ in a clinical sample of adolescents and young adults. METHODS: A total of 204 Young people consecutively referred to a specialist public mental health service in Melbourne, Australia were approached and 150 consented to participate. From this, 136 participants completed both a diagnostic interview and the MASQ. RESULTS: The majority of the sample rated for an Axis-I disorder, with Mood and Anxiety disorders most prevalent. The disorder specific scales of the MASQ significantly discriminated Anxiety (61.0%) and Mood Disorders (72.8%), however, the predictive accuracy for presence of Anxiety Disorders was very low (29.8%). From ROC analyses, a proposed cut-off of 76 was proposed for the depression scale to indicate 'caseness' for Mood Disorders. The resulting sensitivity/specificity was superior to that of the CES-D. CONCLUSION: It was concluded that the depression-specific scale of the MASQ showed good clinical utility, but that the anxiety-specific scale showed poor discriminant validity. PMID- 17868478 TI - Impact of drug classes and treatment availability on the rate of antiretroviral treatment change in the TREAT Asia HIV Observational Database (TAHOD). AB - BACKGROUND: It is critical to understand the pattern of antiretroviral treatment (ART) prescription in different regions of the world as ART procurement needs to be anticipated. We aimed at exploring rates and predictors of ART combination changes in clinical practice in Treat Asia HIV Observational Database (TAHOD). METHODS: Rates of ART changes were examined in patients who started first line triple or more ART combination in TAHOD, and had at least one follow-up visit. Rates of ART changes were summarised per follow-up year, and factors associated with changes assessed using random-effect Poisson regression. The Kaplan-Meier method was used to determine durations of patients in their first, second and third regimen. RESULTS: A total of 1846 patients initiated an ART combination with at least three drugs. Median follow up time for the first treatment was 3.2 years. The overall rate of ART change was 29 per 100-person-year. In univariate analyses, rate of treatment change was significantly associated with exposure category, the country income category, the drug class combination, calendar year and the number of combinations. In multivariate analysis, compared to d4T/3TC/NVP, starting ART with another NNRTI-containing regimen, with PI only or with a triple NRTI regimen was associated with a higher risk of combination change (relative risk (RR) 1.6 (95% CI 1.64 - 1.96), p < 0.001, RR 3.39 (2.76 - 4.16) p < 0.001, RR 6.37 (4.51 - 9.00), p < 0.001). Being on a second or a third combination regimen was also associated with a decreased rate of ART change, compared with first ART combination (RR 0.82 (0.68 - 0.99), p = 0.035, RR 0.77 (0.61 - 0.97), p = 0.024). Sites with fewer than 12 drugs used had an increased rate of treatment changes (1.31 (1.13 - 1.51), p < 0.001). Injecting drug users, and other/unknown exposure was found to increase rate of treatment change (1.24 (1.00 - 1.54), p = 0.055). Percentages of patients who stopped treatment due to adverse events were 31, 27 and 32 in 1st, 2nd and 3rd treatment combinations, respectively. CONCLUSION: Our study suggests that drug availability impacts on ART prescription patterns. Our data, reflecting real clinic use in Asia, suggest that around half of all patients require second combination ART by 3 years after treatment initiation. PMID- 17868479 TI - Snacking behaviours of adolescents and their association with skipping meals. AB - BACKGROUND: Snacking is likely to play an important role in the development of overweight and obesity, yet little is known about the contexts of snacking in adolescents or how snacking may influence other dietary habits, like meal skipping. This study examines the contexts in which adolescents snack and whether these contexts are associated with demographic characteristics of adolescents and with meal skipping. METHODS: A cross-sectional, self-reported online food habits survey was administered to 3,250 secondary students in years seven and nine. The students were drawn from 37 secondary schools in Victoria, Australia during 2004 2005. Frequencies of meal skipping, and snacking in eight contexts, were compared across gender, year level and region of residence. Logistic regressions were performed to examine associations between snacking contexts and meal skipping adjusting for gender and region. RESULTS: The most common contexts for snacking among adolescents were after school (4.6 times per week), while watching TV (3.5 times per week) and while hanging out with friends (2.4 times per week). Adolescents were least likely to snack all day long (0.8 times per week) or in the middle of the night (0.4 times per week). Snacking contexts were variously associated with gender, year level and region. In contrast, meal skipping was associated with gender and region of residence but not year level. Adolescents who reported more frequent snacking on the run, on the way to or from school, all day long, or in the middle of the night were more likely to skip meals. CONCLUSION: These data suggest adolescents snack frequently, especially in their leisure time. In addition, adolescents who snack on the run, on the way to or from school, all day long or in the middle of the night are more likely to skip meals than are adolescents who don't snack at these times. Understanding the contexts in which adolescents snack, and their associations with skipping meals, may assist those involved in the promotion of healthy food habits among adolescents. PMID- 17868480 TI - MiRFinder: an improved approach and software implementation for genome-wide fast microRNA precursor scans. AB - BACKGROUND: MicroRNAs (miRNAs) are recognized as one of the most important families of non-coding RNAs that serve as important sequence-specific post transcriptional regulators of gene expression. Identification of miRNAs is an important requirement for understanding the mechanisms of post-transcriptional regulation. Hundreds of miRNAs have been identified by direct cloning and computational approaches in several species. However, there are still many miRNAs that remain to be identified due to lack of either sequence features or robust algorithms to efficiently identify them. RESULTS: We have evaluated features valuable for pre-miRNA prediction, such as the local secondary structure differences of the stem region of miRNA and non-miRNA hairpins. We have also established correlations between different types of mutations and the secondary structures of pre-miRNAs. Utilizing these features and combining some improvements of the current pre-miRNA prediction methods, we implemented a computational learning method SVM (support vector machine) to build a high throughput and good performance computational pre-miRNA prediction tool called MiRFinder. The tool was designed for genome-wise, pair-wise sequences from two related species. The method built into the tool consisted of two major steps: 1) genome wide search for hairpin candidates and 2) exclusion of the non-robust structures based on analysis of 18 parameters by the SVM method. Results from applying the tool for chicken/human and D. melanogaster/D. pseudoobscura pair wise genome alignments showed that the tool can be used for genome wide pre-miRNA predictions. CONCLUSION: The MiRFinder can be a good alternative to current miRNA discovery software. This tool is available at http://www.bioinformatics.org/mirfinder/. PMID- 17868481 TI - Comparison of protein coding gene contents of the fungal phyla Pezizomycotina and Saccharomycotina. AB - BACKGROUND: Several dozen fungi encompassing traditional model organisms, industrial production organisms and human and plant pathogens have been sequenced recently and their particular genomic features analysed in detail. In addition comparative genomics has been used to analyse specific sub groups of fungi. Notably, analysis of the phylum Saccharomycotina has revealed major events of evolution such as the recent genome duplication and subsequent gene loss. However, little has been done to gain a comprehensive comparative view to the fungal kingdom. We have carried out a computational genome wide comparison of protein coding gene content of Saccharomycotina and Pezizomycotina, which include industrially important yeasts and filamentous fungi, respectively. RESULTS: Our analysis shows that based on genome redundancy, the traditional model organisms Saccharomyces cerevisiae and Neurospora crassa are exceptional among fungi. This can be explained by the recent genome duplication in S. cerevisiae and the repeat induced point mutation mechanism in N. crassa. Interestingly in Pezizomycotina a subset of protein families related to plant biomass degradation and secondary metabolism are the only ones showing signs of recent expansion. In addition, Pezizomycotina have a wealth of phylum specific poorly characterised genes with a wide variety of predicted functions. These genes are well conserved in Pezizomycotina, but show no signs of recent expansion. The genes found in all fungi except Saccharomycotina are slightly better characterised and predicted to encode mainly enzymes. The genes specific to Saccharomycotina are enriched in transcription and mitochondrion related functions. Especially mitochondrial ribosomal proteins seem to have diverged from those of Pezizomycotina. In addition, we highlight several individual gene families with interesting phylogenetic distributions. CONCLUSION: Our analysis predicts that all Pezizomycotina unlike Saccharomycotina can potentially produce a wide variety of secondary metabolites and secreted enzymes and that the responsible gene families are likely to evolve fast. Both types of fungal products can be of commercial value, or on the other hand cause harm to humans. In addition, a great number of novel predicted and known enzymes are found from all fungi except Saccharomycotina. Therefore further studies and exploitation of fungal metabolism appears very promising. PMID- 17868482 TI - PlasmaDNA: a free, cross-platform plasmid manipulation program for molecular biology laboratories. AB - BACKGROUND: Most molecular biology experiments, and the techniques associated with this field of study, involve a great deal of engineering in the form of molecular cloning. Like all forms of engineering, perfect information about the starting material is crucial for successful completion of design and strategies. RESULTS: We have generated a program that allows complete in silico simulation of the cloning experiment. Starting with a primary DNA sequence, PlasmaDNA looks for restriction sites, open reading frames, primer annealing sequences, and various common domains. The databases are easily expandable by the user to fit his most common cloning needs. PlasmaDNA can manage and graphically represent multiple sequences at the same time, and keeps in memory the overhangs at the end of the sequences if any. This means that it is possible to virtually digest fragments, to add the digestion products to the project, and to ligate together fragments with compatible ends to generate the new sequences. Polymerase Chain Reaction (PCR) fragments can also be virtually generated using the primer database, automatically adding to the fragments any 5' extra sequences present in the primers. CONCLUSION: PlasmaDNA is a program available both on Windows and Apple operating systems, designed to facilitate molecular cloning experiments by building a visual map of the DNA. It then allows the complete planning and simulation of the cloning experiment. It also automatically updates the new sequences generated in the process, which is an important help in practice. The capacity to maintain multiple sequences in the same file can also be used to archive the various steps and strategies involved in the cloning of each construct. The program is freely available for download without charge or restriction. PMID- 17868483 TI - Elevated serum beta-human chorionic gonadotropin in nonpregnant conditions. AB - Positive serum beta-human chorionic gonadotropin (beta-hCG) in reproductive-age women generally indicates a pregnancy, and to a lesser extent, gestational trophoblastic disease, ovarian or peripheral germ cell tumor. Besides gynecologic conditions, nongynecologic cancers can be associated with beta-hCG positivity as well. The hormone in these tumors varies from detection by the immunohistochemistry studies of the tumor tissue only to a high serum level. This is illustrated by our case report of a 26-year-old woman who was diagnosed with a spindle cell osteosarcoma of the shoulder. The serum beta-hCG became undetectable after chemotherapy. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians Learning OBJECTIVES: After completion of this article, the reader should be able to recall that elevated serum hCG can be related to pregnancy, gestational neoplasias, and ovarian and nongynecologic tumors and explain that it is important to appreciate that the hCG detected in these conditions may differ in type and be a marker of the success of treatment. PMID- 17868484 TI - Obstetric management of thyroid disease. AB - Timely treatment of thyroid disease during pregnancy is important in preventing adverse maternal and fetal outcome. At present, thyroid testing is performed on symptomatic pregnant women or those with a history of the disease. Hypothyroidism is very often subclinical in nature and not easily recognized without specific screening programs. Even mild maternal thyroid hormone deficiency may lead to neurodevelopment complications in the fetus. Early maternal thyroxine therapy might be beneficial in these women. The main diagnostic indicator of thyroid disease is the measurement of serum thyroid stimulating hormone and free thyroxine. Availability of gestation-age-specific thyroid stimulating hormone (TSH) thresholds is an important aid in the accurate diagnosis and treatment of thyroid dysfunction. Pregnancy-specific free thyroxine thresholds not presently available are also required. Gestational iodine deficiency is still prevalent in some areas of the United Kingdom. Thyroid peroxidase antibody (TPO Ab) in combination with thyroglobulin autoantibody (TgAb) is an accurate predictor of postpartum thyroiditis (PPT). Early screening and treatment of PPT may be justified on the grounds that it is relatively common and causes considerable postpartum morbidity. Large-scale intervention trials are urgently needed to assess the efficacy of preconception or early pregnancy screening for thyroid disorders. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to state that thyroid gland physiology changes with pregnancy, recall that levels of thyroid hormones are gestational-age related, and explain that accurate interpretation of both antepartum and postpartum levels of thyroid hormones are important in preventing pregnancy-related complication secondary to thyroid dysfunction and in the diagnosis and management of postpartum thyroiditis. PMID- 17868485 TI - Elevated HCG outside of pregnancy--diagnostic considerations and laboratory evaluation. AB - Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced by trophoblastic tissues, and its identification is frequently relied upon to establish the diagnosis of pregnancy. Entities other than pregnancy, such as false-positive hCG results, pituitary hCG, exogenous hCG, and both trophoblastic and nontrophoblastic neoplasias, can also cause laboratory assays for hCG to show positive results. Because of their rarity, these conditions are not commonly recognized, and the steps to differentiate between them are not widely known. Discriminating between the causes of elevated hCG in nonpregnant patients can be confusing. An understanding of the differential diagnosis and awareness of available diagnostic modalities are essential for accurate diagnosis and avoidance of potentially harmful treatments. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to state the importance of types of human chorionic gonadotropin (hCG), recall their presence in both trophoblastic and nontrophoblastic neoplasias, and explain how important it is to distinguish between the various causes of an elevated serum hCG to avoid harmful treatments. PMID- 17868486 TI - High folic acid increases cell turnover and lowers differentiation and iron content in human HT29 colon cancer cells. AB - Folate, a water-soluble B vitamin, is a cofactor in one-carbon metabolism and is essential for DNA synthesis, amino acid interconversion, methylation and, consequently, normal cell growth. In animals with existing pre-neoplastic and neoplastic lesions, folic acid supplementation increases the tumour burden. To identify processes that are affected by increased folic acid levels, we compared HT29 human colon cancer cells exposed to a chronic supplemental (100 ng/ml) level of folic acid to cells exposed to a normal (10 ng/ml) level of folic acid, in the presence of vitamin B12 and other micronutrients involved in the folate methionine cycle. In addition to higher intracellular folate levels, HT29 cells at 100 ng folic acid/ml displayed faster growth and higher metabolic activity. cDNA microarray analysis indicated an effect on cell turnover and Fe metabolism. We fully confirmed these effects at the physiological level. At 100 ng/ml, cell assays showed higher proliferation and apoptosis, while gene expression analysis and a lower E-cadherin protein expression indicated decreased differentiation. These results are in agreement with the promoting effect of folic acid supplementation on established colorectal neoplasms. The lower expression of genes related to Fe metabolism at 100 ng folic acid/ml was confirmed by lower intracellular Fe levels in the cells exposed to folic acid at 100 ng/ml. This suggests an effect of folate on Fe metabolism. PMID- 17868487 TI - The responses of serum transferrin receptors to iron supplements in subjects with iron-deficiency erythropoiesis and iron-deficiency anaemia. AB - We aimed to study the response of serum transferrin receptors (sTfR) to Fe supplementation in women of childbearing age with Fe-deficiency erythropoiesis (IDE) and Fe-deficiency anaemia (IDA). Primary screening was performed in 942 women ranging in age from 18 to 45 years. After Fe-related biochemical indices such as serum ferritin, Zn protoporphyrin and Hb were determined, the subjects were divided into four groups: normal, Fe store depletion, IDE and IDA. A total of 131 women were randomly selected from the normal, IDE and IDA groups. Subsequently, seventy-six women with IDE and IDA were given various doses of Fe (14 mg/d for IDE; 28 mg/d for IDA) with ferrous l-threonate capsules for twelve consecutive weeks. After receiving Fe supplements, the levels of Fe and sTfR were determined at weeks 0, 3, 6, 9 and 12. The levels of sTfR in women of childbearing age with IDE and IDA were significantly higher than those in the normal group. After receiving Fe supplements, the levels of sTfR were significantly decreased in women of childbearing age with IDE and IDA, while the levels of serum ferritin were significantly increased. In conclusion, STfR can be used as a reliable indicator for assessing the efficacy of Fe supplements. PMID- 17868488 TI - Phytanic acid: measurement of plasma concentrations by gas-liquid chromatography mass spectrometry analysis and associations with diet and other plasma fatty acids. AB - Epidemiological data suggest that a diet rich in animal foods may be associated with an increased risk of several cancers, including cancers of the prostate, colorectum and breast, but the possible mechanism is unclear. It is hypothesised that phytanic acid, a C20 branched-chain fatty acid found predominantly in foods from ruminant animals, may be involved in early cancer development because it has been shown to up regulate activity of alpha-methylacyl-coenzyme A racemase, an enzyme commonly found to be over-expressed in tumour cells compared with normal tissue. However, little is known about the distribution of plasma phytanic acid concentrations or its dietary determinants in the general population. The primary aim of the present cross-sectional study was to determine circulating phytanic acid concentrations among ninety-six meat-eating, lacto-ovo-vegetarian and vegan women, aged 20-69 years, recruited into the Oxford component of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford). Meat-eaters had, on average, a 6.7-fold higher geometric mean plasma phytanic acid concentration than the vegans (5.77 v. 0.86 micromol/l; P < 0.0001) and a 47 % higher mean concentration than the vegetarians (5.77 v. 3.93 micromol/l; P = 0.016). The strongest determinant of plasma phytanic acid concentration appeared to be dairy fat intake (r 0.68; P < 0.0001); phytanic acid levels were not associated with age or other lifestyle factors. These data show that a diet high in fat from dairy products is associated with increased plasma phytanic acid concentration, which may play a role in cancer development. PMID- 17868489 TI - Effect of the LoBAG30 diet on blood glucose control in people with type 2 diabetes. AB - In subjects with untreated type 2 diabetes, we previously determined that a weight-maintenance, non-ketogenic diet containing 30 % protein, 50 % fat and 20 % carbohydrate (30:50:20) decreased the percentage total glycohaemoglobin (%tGHb) by 2.2 % glycohaemoglobin over 5 weeks compared to a diet recommended for the American public (protein-fat-carbohydrate 15:30:55). Both the fasting and postprandial glucose were decreased. The objective of the present study was to determine if increasing the carbohydrate content from 20 to 30 % at the expense of fat would still provide a similar effect on %tGHb, fasting and postprandial glucose concentration. Eight men with untreated type 2 diabetes were studied over a 5-week period. Results at the beginning (standard diet) and end of the 5-week study were analysed. Body weight was stable. Fasting glucose concentration decreased by 40 %; 24 h glucose area response decreased by 45 %. Insulin did not change. Mean %tGHb decreased by 1.7 (from 10.8 to 9.1 %), and was still decreasing linearly at 5 weeks. In conclusion, a high-protein, 30 % carbohydrate diet could be a patient-empowering method of improving the hyperglycaemia of type 2 diabetes without pharmacologic intervention. Long-term effects and general applicability of this diet remain to be determined. PMID- 17868490 TI - Effect of prebiotic supplementation on a probiotic bacteria mixture: comparison between a rat model and clinical trials. AB - The effects of a probiotic mixture (PRO), supplemented with either galacto oligosaccharide (GOS) or polydextrose (PDX), on cell numbers of lactic acid bacteria (LAB) and bifidobacteria (BIF) were studied in conventional rats and healthy human subjects. In rats the baseline BIF cell numbers were below the detection limit and were increased by the 2-week GOSPRO intervention. In contrast baseline LAB numbers in rats were high and not affected by the treatments. The human study consisted of two independent but concurrent trials; both started with PRO followed by GOSPRO or PDXPRO periods. In the human subjects variation in numbers of BIF and LAB were high. The GOSPRO group exhibited high counts of faecal LAB and BIF at the start and showed little or no effects of the interventions. In contrast, the PDX group had low faecal LAB and BIF numbers at the start and clearly increased cell numbers of BIF after the PDXPRO period, and LAB after the PRO and PDXPRO period, compared with the run-in period. We propose here that responses to pro- and prebiotics are dependent on baseline numbers of LAB and/or BIF, and that the conventional rat model does not predict well the treatment responses in humans. The survival of PRO was presumably enhanced by the use of prebiotic supplementation and advocates the use of particular combinations of pro- and prebiotics. PMID- 17868491 TI - Gender-specific modulation of tumorigenesis by folic acid supply in the Apc mouse during early neonatal life. AB - Epidemiological studies suggest an inverse association between folic acid intake and colorectal cancer risk. Conversely, conventional treatment of existing tumours includes the use of folate antagonists. This suggests that the level of exposure to folate and its timing in relation to stage of tumorigenesis may be critical in determining outcomes. We hypothesised that folic acid depletion in utero and during early neonatal life may affect tumorigenesis in offspring. To investigate this hypothesis, female C57Bl6/J mice were randomised to a folic acid adequate (2 mg folic acid/kg diet) or folic acid depleted diet (0.4 mg folic acid/kg) from mating with Apc+/Min sires and throughout pregnancy and lactation. At weaning the Apc+/Min offspring were randomised to a folic acid adequate (2 mg folic acid/kg diet) or depleted (0.26 mg folic acid/kg diet) diet, creating four in utero/post-weaning dietary regimens. At 10 weeks post-weaning, mice were killed and the intestinal tumour number and size were recorded. Folic acid depletion during pregnancy and post-weaning reduced erythrocyte folate concentrations in offspring significantly. Folic acid depletion during pregnancy and lactation did not affect tumour multiplicity or size. However, female mice fed normal folic acid diets post-weaning had more, and larger, tumours when compared with depleted females and both depleted and adequate folic acid fed males. These data suggest that folate depletion post-weaning was protective against neoplasia in female Apc+/Min mice and highlights the need for further investigation of the optimal timing and dose of folic acid supplementation with regard to colorectal cancer risk. PMID- 17868492 TI - Dietary inulin affects the expression of intestinal enterocyte iron transporters, receptors and storage protein and alters the microbiota in the pig intestine. AB - Inulin, a linear beta fructan, is present in a variety of plants including chicory root and wheat. It exhibits prebiotic properties and has been shown to enhance mineral absorption and increase beneficial bacteria in the colon. The aim of the present study was to assess the effect of dietary inulin on the gene expression of selected intestinal Fe transporters and binding proteins. Anaemic piglets at age 5 weeks were allocated to a standard maize-soya diet (control) or the same diet supplemented with inulin at a level of 4 %. After 6 weeks, the animals were killed and caecum contents and sections of the duodenum and colon were removed. Segments of the genes encoding for the pig divalent metal transporter 1 (DMT1) and duodenal cytochrome-b reductase (Dcytb) were isolated and sequenced. Semi-quantitative RT-PCR analyses were performed to evaluate the expression of DMT1, Dcytb, ferroportin, ferritin, transferrin receptor (TfR) and mucin genes. DMT1, Dcytb, ferroportin, ferritin and TfR mRNA levels in duodenal samples were significantly higher in the inulin group (P < or = 0.05) compared with the control. In colon, DMT1, TfR and ferritin mRNA levels significantly increased in the inulin group. Additionally, the caecal content microflora was examined using 16S rDNA targeted probes from bacterial DNA. The Lactobacillus and Bifidobacterium populations were significantly increased in the inulin group (P < or = 0.05) compared with the control group. These results indicate that dietary inulin might trigger an up regulation of genes encoding for Fe transporters in the enterocyte. The specific mechanism for this effect remains to be elucidated. PMID- 17868493 TI - Absolute bioavailability and dose-dependent pharmacokinetic behaviour of dietary doses of the chemopreventive isothiocyanate sulforaphane in rat. AB - Sulforaphane is a naturally occurring isothiocyanate with promising chemopreventive activity. An analytical method, utilising liquid chromatography MS/MS, which allows the determination of sulforaphane in small volumes of rat plasma following exposure to low dietary doses, was developed and validated, and employed to determine its absolute bioavailability and pharmacokinetic characteristics. Rats were treated with either a single intravenous dose of sulforaphane (2.8 micromol/kg) or single oral doses of 2.8, 5.6 and 28 mumol/kg. Sulforaphane plasma concentrations were determined in blood samples withdrawn from the rat tail at regular time intervals. Following intravenous administration, the plasma profile of sulforaphane was best described by a two compartment pharmacokinetic model, with a prolonged terminal phase. Sulforaphane was very well and rapidly absorbed and displayed an absolute bioavailability of 82 %, which, however, decreased at the higher doses, indicating a dose-dependent pharmacokinetic behaviour; similarly, Cmax values did not rise proportionately to the dose. At the highest dose used, the rate of absorption constant k(ab), biological half-life t(1/2) and apparent volume of distribution decreased significantly. It is concluded that in the rat orally administered sulforaphane is rapidly absorbed, achieving high absolute bioavailability at low dietary doses, but dose-dependent pharmacokinetics was evident, with bioavailability decreasing with increasing dose. PMID- 17868494 TI - How do Chinese patients with dementia rate their own quality of life? AB - OBJECTIVE: This study examines the psychometric properties and clinical experience in using the Mandarin translation of the Quality of Life-Alzheimer's Disease (QoL-AD) instrument in Chinese patients with dementia in Singapore. METHODS: A Mandarin version of QoL-AD was established following standard guidelines for transcultural adaptation of QoL measures. The instrument was administered to 70 patient-carer dyads; patients with severe dementia (MMSE < 10) were excluded. Reliability by internal consistency and test-retest, and construct validity by correlating the known domains of QoL-AD with validity measures for the respective domains, was performed. Guidelines for Rating Awareness Deficits (GRAD) measured patients' insight into their deficits. RESULTS: Three patients were not able to complete the QoL-AD. Internal consistency (Cronbach's alpha) was high for both patient (0.9) and carer (0.8) QoL-AD ratings, as was test-retest reliability, intraclass correlation coefficient (ICC) 0.7 and 0.8 respectively. Correlation of QoL-AD with domain measures was moderate for carer ratings (0.21 < r < 0.51) and poor for patient (-0.17 < r < 0.13). Patient self-rated QoL correlated poorly with, and was significantly higher than, carer-rated QoL. Correlation between patient and carer QoL-AD was stronger in patients with better insight (GRAD 3-4). CONCLUSIONS: The results suggest that while the Mandarin version of QoL-AD can be used reliably in our population, patients' self perceived QoL can be different from carer ratings and from objective QoL measures. The disparity can be attributed to patients' poor insight, denial, fear of "losing face," normalization and accommodation of standards with aging. The patients' lack of education and seclusion from Western cultural exposure are also contributory. PMID- 17868495 TI - Mild parkinsonian signs and psycho-behavioral symptoms in subjects with mild cognitive impairment. AB - BACKGROUND: Mild cognitive impairment (MCI) may be accompanied by extra pyramidal signs (EPS), which are related to the severity and type of cognitive impairment. We aimed to elucidate further the relationship between MCI and EPS, analyzing the correlation between the severity of EPS and cognitive functions, and the presence of EPS and neuro-psychiatric features. METHODS: Data were obtained from a longitudinal study of 150 MCI outpatients. Participants underwent a clinical assessment including the Unified Parkinson Disease Rating Scale, the Neuropsychiatric Inventory, the Tinetti Scale, and a standardized neuropsychological battery. Mild EPS could be defined as being present (MCI with mild EPS) using a subscale of UPDRS, based on three specific symptoms: bradykinesia, rigidity and tremor. RESULTS: The two groups, one with mild EPS (24%) and one without EPS (76%), differed in gait abnormalities and presence of extrapyramidal symptoms. Groups did not differ in terms of general cognitive functions evaluated using the Mini-mental State Examination, while subjects with MCI with mild EPS performed significantly worse than those with MCI without EPS in total global score and in non-memory items of the Alzheimer's Disease Assessment Scale. Moreover, severity of EPS was significantly correlated with low performance on executive functions and with high performance on episodic memory. The group with MCI with mild EPS were observed to have a greater prevalence of patients with anxiety, depression, apathy and sleep disturbances than in MCI without EPS. CONCLUSION: MCI may be associated with mild parkinsonian signs, the severity of which are related to the severity of cognitive impairment, in particular of non-memory functions, and to a differential pattern of psycho behavioral symptoms. PMID- 17868496 TI - Subjective socioeconomic status as a predictor of long-term care staff burnout and positive caregiving experiences. AB - BACKGROUND: The potentially negative consequences associated with providing care to older adults are well documented. Recently, there has been an increasing interest in the positive aspects associated with caregiving. Both aspects are believed to represent a continuum of caregiving experiences. Long-term care (LTC) staff members often report high levels of burnout associated with their work. Whereas several job characteristics and objective indicators of socioeconomic status have been identified as potential predictors of LTC staff caregiving experiences, the role of subjective socioeconomic status (i.e. one's view of one's place in society) has not yet been evaluated. METHODS: A cross-sectional design of 122 LTC staff members. LTC staff completed the Maslach Burnout Inventory and the Positive Aspects of Caregiving questionnaire. They also completed questions about job characteristics (i.e. staff-to-resident ratio, number of hours worked per day, and years of experience working with older adults), objective sociodemographic variables (i.e. level of education, professional affiliation), and subjective socioeconomic indicator (i.e. MacArthur Scale of Subjective Social Status). Hierarchical regression analyses were conducted to identify the unique contribution of job characteristics, objective socioeconomic status, and subjective socioeconomic status to LTC staff caregiving experiences. RESULTS: Subjective socioeconomic status remained a significant predictor of LTC staff experience even once job characteristics and objective indicators of socioeconomic status were entered into the model. Those who placed themselves higher on the subjective social ladder reported higher levels of positive caregiving experiences and lower levels of burnout. CONCLUSIONS: Building a sense of community identity and improving one's status within the community might result in lower levels of burnout and better caregiving experiences among LTC staff. PMID- 17868497 TI - Embolization of a pulmonary arterial pseudoaneurysm with endovascular coils. AB - Unrecognized pseudoaneurysm or rupture of a pulmonary artery is a rare but potentially catastrophic complication of pulmonary arterial catheterization. Herein, we describe a teenage patient with a pulmonary arterial pseudoaneurysm, probably iatrogenic, who presented with haemoptysis following catheterization of the right heart. The pseudoaneurysm was successfully embolized using coils inserted by catheter. Increased awareness of this lesion, its rapid recognition, and prompt therapy are the keys to a successful outcome. PMID- 17868498 TI - Proximal origin and hypoplasia of the left pulmonary artery in association with chromosome 22q11 deletion, right aortic arch, and persistently patent right-sided arterial duct. PMID- 17868499 TI - The effect of atrial septostomy on the concentration of brain-type natriuretic peptide in patients with idiopathic pulmonary arterial hypertension. AB - Atrial septostomy has improved haemodynamics and clinical symptoms in selected patients with idiopathic pulmonary arterial hypertension. We found that, in 5 patients with idiopathic pulmonary arterial hypertension, septostomy resulted in decreased levels of brain-type natriuretic peptide, and improvement in symptoms of cardiac failure, suggesting that serial measurements of the peptide may have clinical utility. PMID- 17868500 TI - Timing of removal of pacing wires following paediatric cardiac surgery. AB - BACKGROUND: Temporary percutaneous epicardial pacing wires are routinely placed in children following cardiac surgery. There is uncertainty in clinical practice about the optimum timing for their removal, and practice varies widely both within and between different institutions. AIM: The aim of our study was to describe the use of temporary pacing in children undergoing cardiac surgery. METHODS: We performed a prospective audit of 140 children following cardiac surgery in two institutions. Information on diagnosis, surgical procedure, occurrence of arrhythmias, use of pacing wires, timing of removal of the wire, and complications related to removal was recorded on a daily basis from clinical records. RESULTS: We studied 140 patients undergoing a total of 141 operations. Of these, 39 (28%) required pacing postoperatively. In 38, pacing was required within the first 24 hours. One patient, who was in nodal rhythm for the first 24 hours, required pacing on the second postoperative day, while 29 patients required pacing beyond the first 24 hours. No patient in sinus rhythm on the first postoperative day required new pacing after this time. The median time to removal of the pacing wires was 4.5 days, with an inter-quartile range from 2 to 9 days. Complications included malfunction of atrial wires in 2 patients. CONCLUSIONS: Our study shows that no patient who was in sinus rhythm for the first 24 hours post-operatively required pacing before their discharge from hospital. This suggests that, in those patients in a stable state of sinus rhythm, and who have not required pacing within the first 24 hours, it may be safe to remove pacing wires after 24 hours. This could be timed to coincide with the removal of chest drains, thus avoiding the need for multiple distressing procedures. PMID- 17868502 TI - Cardiac history, prior depression and personality predict course of depressive symptoms after myocardial infarction. AB - BACKGROUND: Although many studies have focused on post-myocardial infarction (MI) depression, there is limited information about the evolution and determinants of depressive symptoms in the first year post-MI. Therefore we examined (1) the course of depressive symptoms during the first year post-MI and (2) the predictors of these symptom trajectories. METHOD: To assess depressive symptoms, 287 patients completed the Beck Depression Inventory during hospitalization for MI, and 2, and 12 months post-MI. Personality was assessed with the Type-D scale during hospitalization. We used latent class analysis to examine the evolution of depressive symptoms over a 1-year period and multinomial logit regression analyses to examine predictors of these symptom trajectories. RESULTS: The course of depressive symptoms was stable during the first year post-MI. Four groups were identified and classified as non-depressed [40%, intercept (IC) 2.52], mildly depressed (42%, IC 6.91), moderately depressed (14%, IC 13.73) or severely depressed (4%, IC 24.54). In multivariate analysis, cardiac history (log OR(severe) 2.93, p=0.02; log OR(moderate) 1.81, p=0.02; log OR(mild) 1.46, p=0.01), history of depression (log OR(severe) 4.40, p<0.001; log OR(moderate) 1.97, p=0.03) and Type-D personality (log OR(severe) 4.22, p<0.001; log OR(moderate) = 4.17, p<0.001; log OR(mild) 1.66, p=0.02) were the most prominent risk factors for persistence of depressive symptoms during the first year post MI. CONCLUSIONS: Symptoms of depression tend to persist during the first year post-MI. Cardiac history, prior depression and Type-D personality were identified as independent risk factors for persistence of depressive symptoms. The results of this study strongly argue for routine psychological screening during hospitalization for acute MI in order to identify patients who are at risk for chronicity of depressive symptoms and its deleterious effects on prognosis. PMID- 17868501 TI - Chronic treatment with aripiprazole induces differential gene expression in the rat frontal cortex. AB - Chronic treatment of antipsychotic drugs can modulate gene expression in the brain, which may underscore their clinical efficacy. Aripiprazole is the first approved antipsychotic drug of the class of dopamine D2 receptor partial agonist, which has been shown to have similar efficacy and favourable side-effects profile compared to other antipsychotic drugs. This study aimed to identify differential gene expression induced by chronic treatment of aripiprazole. We used microarray based gene expression profiling technology, real-time quantitative PCR and Western blot analysis to identify differentially expressed genes in the frontal cortex of rats under 4 wk treatment of aripiprazole (10 mg/kg). We were able to detect ten up-regulated genes, including early growth response gene 1, 2, 4 (Egr1, Egr2, Egr4), chromobox homolog 7 (Cbx7), cannabinoid receptor (Cnr1), catechol-O-methyltransferase (Comt), protein phosphatase 2c, magnesium dependent (Ppm2c), tachykinin receptor 3 (Tacr3), Wiscott-Aldrich syndrome-like gene (Wasl) and DNA methyltransferase 3a (Dnmt3a). Our data indicate that chronic administration of aripiprazole can induce differential expression of genes involved in transcriptional regulation and chromatin remodelling and genes implicated in the pathogenesis of psychosis. PMID- 17868503 TI - Efficacy, tolerability and comfort of a 0.3% hypromellose gel ophthalmic lubricant in the treatment of patients with moderate to severe dry eye syndrome. AB - OBJECTIVE: To evaluate efficacy, safety and comfort of a 0.3% hypromellose (HM) eye gel (GenTeal Lubricant Eye Gel), with a sodium perborate preservative system and carbomer gelling agent, in patients with dry eye. RESEARCH DESIGN AND METHODS: Patients with moderate-to-severe dry eye syndrome were enrolled in this open label study and assessed at three visits; a screening consultation (baseline) and two follow-up visits on day 14 (+/- 4 days) and day 28 (+/- 4 days). All screening, evaluation and follow-up visits were carried out at the Tauber Eye Center (formerly the Hunkeler Eye Center), Kansas City. Patients were treated with the product over a 4-week period. They were instructed to use the product at least two times daily, more if necessary, with one drop instilled into the conjunctive sac of both eyes. MAIN OUTCOME MEASURES: Efficacy was measured by ocular symptoms (burning, stinging, foreign body sensation, dryness, pain/soreness and photophobia), ocular signs (eyelid erythema, bulbar conjunctival injection and corneal superficial punctate keratitis score), tear breakup time and global assessment of ocular comfort. Tolerability measures were change from baseline in best corrected Snellen visual acuity and monitoring of adverse events. RESULTS: Thirty-seven patients completed this study. The mean sum symptom score at each visit was significantly lower compared with baseline with approximately 30% reduction in the sum symptom score at 2 weeks and approximately 33% at 4 weeks after treatment initiation (p < 0.001). Mean individual symptom scores for dryness, stinging and foreign body sensation decreased by approximately 40% at the end of the study (p < 0.02). Tear breakup time increased from baseline by 53% and 59% at 2 and 4 weeks, respectively (p < 0.001). The proportion of patients reporting a global evaluation of slightly better or much better was approximately 74% at 2 weeks and 78% at 4 weeks after treatment initiation. The product was well tolerated, with one related adverse event reported. CONCLUSIONS: In a small, open-label study, this 0.3% HM eye gel showed statistically significant effects in relieving ocular symptoms and provides a well-tolerated formula that effectively reduced symptoms and improved ocular comfort in patients with dry eye syndrome. PMID- 17868504 TI - Long dosing intervals in the treatment of postmenopausal osteoporosis. AB - BACKGROUND: Osteoporosis is a common disease associated with diminished bone strength and increased risk of fracture. With the aging of the population, the number of people with osteoporosis, particularly postmenopausal women, is expected to increase. There are excellent tools for diagnosing osteoporosis and widely available treatments that are safe and effective. Nevertheless, osteoporosis is underdiagnosed and undertreated. Even among those who are diagnosed and treated, widespread nonadherence with treatment regimens undermines the efficacy of osteoporosis therapy. PURPOSE: To examine the pharmacological options for the treatment of postmenopausal osteoporosis and the influence of extended dosing intervals upon outcomes, medication adherence, and patient preference. METHODS: A Medline and Cochrane Review database search was conducted for appropriate clinical trials, meta-analyses, and systematic reviews published between 1987 and 2007. FINDINGS: The causes of nonadherence include poor understanding of the consequences of a silent disease, concern regarding potential side-effects of medications, the inconvenience associated with administration of some osteoporosis medications, and medication costs. The recent development of effective oral and injectable osteoporosis medications that can be given with long dosing intervals may improve patient adherence. Less frequent dosing lessens the inconvenience of administration, and dosing by injection assures that the medication is 100% bioavailable. Osteoporosis patients have shown a preference for monthly bisphosphonate dosing compared with weekly dosing. CONCLUSION: Enhanced adherence with new dosing regimens can be expected to improve treatment efficacy, reduce fracture risk, and lessen the burden of osteoporosis on patients and society. Further study is required to fully elucidate the relationship between extended dosing, adherence, and positive outcomes. PMID- 17868505 TI - Comment and reply on: International Society for Medical Publication Professionals (ISMPP) position statement: the role of the professional medical writer. PMID- 17868506 TI - Eco-friendly dentistry: not a matter of choice. PMID- 17868507 TI - Evidence-based decision making: should the general dentist adopt the use of the VELscope for routine screening for oral cancer? PMID- 17868508 TI - A magic wand for the community dental office? Observations from the British Columbia Oral Cancer Prevention Program. PMID- 17868509 TI - I've learned a thing or two... PMID- 17868510 TI - Effectiveness of 2 scavenger mask systems for reducing exposure to nitrous oxide in a hospital-based pediatric dental clinic: a pilot study. AB - Chronic exposure to elevated ambient air levels of nitrous oxide during nitrous oxide/ oxygen (N2O/2) sedation can result in deleterious side effects to dentists and auxiliary staff. A sampling survey was done in the outpatient dental clinic at the Hospital for Sick Children to determine whether airborne nitrous oxide (N2O) gas concentrations were within established regulatory limits. The effectiveness of 2 scavenger mask systems, the Matrix Medical single-mask system and the Porter/Brown double-mask system, for reducing airborne contamination in a clinical environment during the treatment of pediatric dental patients was compared in a pilot study. The results indicated that the double-mask system more effectively minimized N2O exposure during N2O/O2 sedation of outpatients for a variety of clinical pediatric dental procedures. PMID- 17868511 TI - Domestic violence and its relation to dentistry: a call for change in Canadian dental practice. AB - Domestic violence (DV), now a national health concern, has pervasive effects at both the individual and societal levels. Women are the primary victims of DV; their lifetime prevalence has been reported to be 20%-53.8%. The sequelae of violence include increased acute and chronic health care utilization, psychological harm and a wide range of physical injuries. Head and neck injuries are the most common result of violence, and many women seek dental treatment following abuse. Dentists are in a unique position to identify abused victims and intervene. However, they are not well trained to identify victims of DV, and they lack appropriate resources to manage identified victims. Moreover, of the many health professionals surveyed, dentists feel the least responsible for intervening in cases of DV, and interventions by dentists are minimal. Barriers to screening for DV occur at the patient, provider and system levels, but they can be overcome with increased education. DV education, assessment and management should be a priority, so that dentists can help improve the lives of the many women faced with abuse. PMID- 17868512 TI - Lawsuit against a dentist related to serious ocular infection possibly linked to water from a dental handpiece. AB - This case report highlights the risks that may be associated with amoebae in the water of a dental unit. A woman with contact lenses visited her dentist for replacement of a bridge. During the treatment, a stream of water was directed from the handpiece into her right eye. Because of subsequent pain in the eye, the patient consulted several ophthalmologists, who discovered abrasive lesions of the cornea and inflammation. Despite antibacterial and anti-inflammatory treatments, the patient"s visual acuity declined gradually over a period of several days. A microbiological examination nearly 2 months later revealed amoebae in corneal samples. A lawsuit against the dentist was initiated. Although a causal relation with the dental treatment was rejected by the judge in this case, high numbers of amoebae in the water of dental units can present a risk if a patient with pre-existing corneal lesions is splashed. According to the precautionary principle, complete evidence of risk does not have to exist to institute measures to protect individuals and society from that risk. This case reinforces the importance of having patients wear safety glasses during dental treatments and of dental personnel draining the waterlines of dental units, as recommended by the Canadian Dental Association. PMID- 17868513 TI - Coronal sealing ability of a new root canal filling material. AB - BACKGROUND AND OBJECTIVE: To date, many different materials have been proposed for root canal fillings, but gutta-percha (used with various types of sealers) has remained the material of choice for over a century. A new root canal obturation system, the Epiphany endodontic obturation system, has been developed to replace gutta-percha and traditional sealers for root canal obturation. The purpose of this study was to evaluate the coronal sealing ability of the new endodontic obturation system. MATERIALS AND METHODS: Seventy-two maxillary and mandibular single-rooted human teeth extracted for periodontal reasons were used. The root canals were instrumented using the step-back technique and were irrigated with 5.25% sodium hypochlorite. The smear layer was removed by washing in 10 mL of 17% ethylenediamine tetra-acetic acid (EDTA). The specimens were randomly divided into 3 groups (group 1 to be filled with gutta-percha and AH 26 sealer, group 2 with gutta-percha and AH plus sealer, and group 3 with Epiphany self-etch sealer and Resilon obturating material) and obturated by lateral condensation. Teeth were centrifuged at 30 g for 5 minutes in 2% methylene blue dye solution to allow evaluation of any coronal leakage. The tooth roots were longitudinally grooved with a diamond disk and split with a chisel. Dye penetration was measured from the coronal to the apical part of the root canal using a stereomicroscope with ocular micrometer, and the mean leakage value for each group was calculated and recorded. RESULTS: The 6 positive control specimens had total dye penetration of the root canal system, whereas the 6 negative control teeth had no dye penetration into the roots. All of the experimental groups demonstrated some degree of coronal leakage. Coronal leakage was greatest in the teeth filled with gutta-percha and AH 26 sealer and least in teeth treated with Epiphany sealer and Resilon core material. These differences in coronal leakage were statistically significant (p < 0.05). CONCLUSION: All of the root canal filling materials tested in this evaluation yielded a satisfactory seal; however, the Epiphany root canal filling system exhibited the least coronal leakage. PMID- 17868514 TI - External cervical resorption associated with traumatic occlusion and pyogenic granuloma. AB - This report describes a rare situation in which external cervical resorption was associated with gingival enlargement (pyogenic granuloma) in the upper left central incisor (tooth 21) in a 28-year-old man. Tissue from the lesion was examined histopathologically; periodontal, endodontic and restorative treatments were performed; and the occlusal disharmony, which had resulted in traumatic occlusion, was corrected. Three years after these treatments, the gingiva is normal and healthy and there is no sign of recurrence of the pathologic enlargement. The patient"s periodontal condition is now routinely evaluated. In the presence of gingival enlargement resulting from inflammation, traumatic occlusion can cause progressive external root resorption. PMID- 17868515 TI - Exfoliative cheilitis: report of a case. AB - Exfoliative cheilitis, one of a spectrum of diseases that affect the vermilion border of the lips, is uncommon and has no known cause. However, factors such as stress and some psychiatric conditions are associated with the onset of the disease. This condition is disabling because esthetics and normal functions such as eating, speaking and smiling are compromised. The lack of specific treatment makes exfoliative cheilitis a chronic disease that radically affects a person"s life. This report attempts to further investigate the clinical course of the disease and provides detailed illustrations of the cyclical nature of the disease. PMID- 17868516 TI - [Study of the pharmacotherapy prescribed for older-adult in a Brazilian long-term care facility]. AB - OBJECTIVE: this study evaluated the medication prescribed to older-adults residing in a long-term facility in the Brazilian Federal District. MATERIAL AND METHODS: social-demographic parameters as well the overall degree of disability and autonomy of the subjects were investigated. Regarding the pharmacotherapy, qualitative and quantitative aspects of the medication were assessed, including the mean number of drugs, most prescribed pharmacological classes and principles, appropriateness to the age strata and agreement to lists of essential drugs. RESULTS: in our setting, the female gender constituted a predisposing condition to an increased number of prescriptions, whereas polypharmacy and a favorable level of autonomy have played roles of main risk factors for the potential onset of drug-related problems. CONCLUSIONS: the occurrence of polypharmacy coupled to potentially serious problems related to these drugs allow to conclude that the pharmacotherapy employed for this group of older-adults present questionable therapeutical value, at least on what concerns some medications, prompting attention to the model of medical and pharmaceutical assistance provided for this population. PMID- 17868517 TI - [Preventable drug-related morbidity: determining valid indicators for primary care in Portugal]. AB - Preventable drug-related morbidity (PDRM) indicators are operational measures of therapeutic risk management. These clinical indicators, which cover a wide range of drugs, combine process and outcome in the same instrument. They were developed in the US and have been validated for primary care settings in the US, UK and Canada. This study is part of a research programme; it aimed to determine a valid set of PDRM indicators for adult patients in primary care in Portugal. Face validity of 61 US and UK-derived indicators translated to Portuguese was preliminarily determined by means of a postal questionnaire using a purposive sample of four Portuguese pharmacists with different backgrounds. Preliminary content validity of indicators approved in the previous stage was determined by cross-checking each definition of PDRM with standard drug information sources in Portugal. Face and content validity of indicators yielded by preliminary work were then established by a 37 expert panel (20 community pharmacists and 17 general practitioners) using a two-round Delphi survey. Data were analysed using SPSS release 11.5. Nineteen indicators were ruled out in preliminary validation. Changes were made in the content of eight of the remaining 42 indicators; these were related to differences in the drugs being marketed and patterns of drug monitoring between countries. Thirty-five indicators were consensus approved as PDRM for adult patients in Portuguese primary care by the Delphi panel. PMID- 17868518 TI - [Multivaried analysis of the interaction between quality of life and physical capacities for people occupationally intoxicated by mercury]. AB - INTRODUCTION: One important aggression to human biology is constituted by metallic mercury intoxication, mainly expressed by neuropsychiatric disorders. OBJECTIVE: To explore interaction between the domains of Quality of Life (QoL.) and neuro-muscular evidences in intoxicated people by the metal within an urban industrial environment. MATERIAL AND METHODS: 47 patients have been assessed, through SF36 application and semiological tests. Multiple regression was performed and, to test parameters estimated in adjustments, Student t test was used. RESULTS: Although there are low scores present in the instrument, there have been noticed good results in physical capacities. Muscular strength seems to be an influencing variable on physical and social functioning and mental health (p<0.05). Motor coordination influence on Vitality (p <0.05) was also remarked. As to equilibrium, it presents a negative interaction (p <0.03) with social functioning. CONCLUSIONS: Neuropsychiatric disorders influence negatively QoL perception, making people to subestime their motor performances. Complementarily, it is distinguished strength as physical capacity that presents positive interaction with the subjective perception of QV. PMID- 17868519 TI - [Breast cancer mortality trend in Portugal (1955-2002)]. AB - INTRODUCTION: In the last decade there were significant changes in breast cancer mortality that is declining since the 90 s in several countries. The aim of this study was to quantify the variation of the female breast cancer mortality rates, in Portugal and in different regions of the country, considering the changes in the trends. PATIENTS AND METHODS: Breast cancer mortality rates and the number of deaths were obtained from the World Health Organization, for the years from 1955 to 2002, and the number of deaths and population in each region were obtained from the publication Risco de Morrer em Portugal. Age-standardized rates were computed by the direct method, using the European standard population. Joinpoint regression analyses were performed to identify the years in which changes in trends have occurred, and to estimate the annual percent changes in each period, for the age groups 35-74, 35-44, 45-54, 55-64 and 65-74 years. The annual variation was computed for each Portuguese region from 1990 to 2002. RESULTS: Breast cancer mortality rates increased 1.55%/year (95% Confidence Interval (CI): 1.43 to 1.68) between 1955 and 1992 and changed -2.02%/year (95%CI: -2.81 to 1.31) from 1992 to 2002 in women aged 35 to 74 years. No significant differences were observed in the joinpoints or the estimated annual percent changes across age strata. At a regional level, the mortality trends between 1990 and 2002 were inversely associated with the rates at the beginning of this period (r= -0.74, p <0.001), the larger decline being observed in Lisbon, with rates varying -3.58%/ year (95% CI: -5.30 to -1.48). CONCLUSION: A decrease in breast cancer mortality has been observed in Portugal in the early 90 s, with an estimated annual percent change of -2%/year in the last decade. The decline in mortality correlated positively with the rates at the beginning of the period. PMID- 17868520 TI - [Diabetic nephropathy: glomerular filtration rate and estimated creatinine clearance]. AB - OBJECTIVE: To assess in diabetic nephropathy, the accuracy of estimated creatinine clearance (calculated with the Cockroft Gault formula) and the clearance of the Tc99m-DTPA, to measure the glomerular filtration rate (GFR). PATIENTS AND METHODS: We analysed the GFR measure by Tc99m-DTPA method and the estimated by the Cockroft Gault formula, in 21 subjects with type 1 or type 2 diabetes. RESULTS: There was a strong positive correlation between the two methods but the Cockroft Gault formula underestimated the GFR. CONCLUSIONS: The formula gives a accurate estimates of GFR, when GFR is <100 ml/min/1,73 m2. Beside the underestimation, the formula could be used in the management of diabetic nephropathy because the repeated isotope assessments of renal function are impracticable. PMID- 17868521 TI - [Importance of the radiographic sign of fecal loading in the cecum for the differential diagnosis of acute appendicitis]. AB - BACKGROUND: Although the radiographic characteristics of acute appendicitis have been well documented, the value of plain abdominal radiography has not been completely studied. Therefore, the purpose of this investigation was to verify a new radiographic sign: the presence of fecal loading in the cecum. METHODS: 470 consecutive patients of both sexes were admitted to the hospital due to acute abdomen and pain localized in the right flank were studied prospectively. The patients were divided into four groups: Group 1 (n = 170) - diagnosed with acute appendicitis and subdivided into two subgroups: Subgroup 1A - (n = 100) - patients submitted to an abdominal radiographic study a few hours before surgical treatment, Subgroup 1B - (n = 70) - patients submitted to two abdominal radiographic studies, one before the surgical procedure and the other the following day; Group 2 (n = 100) -patients of both sexes with right nephrolithiasis submitted to an abdominal radiography during the episode of pain caused by the lithiasis; Group 3 (n = 100) - women diagnosed with right acute inflammatory pelvic disease that underwent an abdominal radiographic study during the pain incident; Group 4 (n = 100) - patients of both sexes operated upon to treat acute cholecystitis submitted to abdominal radiography during the pain episode that preceded the surgical procedure. All of the radiographs were plain with an anteroposterior view of the abdomen. RESULTS: The sign of fecal loading in the cecum was present in 97 patients of Subgroup 1A, in 68 patients of Subgroup 1B, in 19 patients of Group 2, in 12 patients of Group 3 and in 13 patients of Group 4. During the postoperative period the radiographic sign disappeared in 66 of the 68 cases that had presented with the sign. The sensitivity of the radiographic sign for acute appendicitis was 97,05% and its specificity was 85,33%. The positive predictive value for acute appendicitis was 78,94% and its negative predictive value was 98,08%. CONCLUSIONS: The radiographic image of fecal loading in the cecum is associated with acute appendicitis. The image usually disappears soon after the appendix is removed. This sign is uncommon in other acute inflammatory diseases of the right side of the abdomen. When a diagnosis of acute appendicitis is suspected, the absence of this sign indicates great possibility of a different diagnosis. PMID- 17868522 TI - [Ventilatory dysfunction in motor neuron disease: when and how to act?]. AB - Amyotrophic lateral sclerosis is a devastating progressive neurodegenerative disorder, involving motor neurons in the cerebral cortex, brainstem and spinal cord. Mean duration of survival from the time of diagnosis is around 15 months, being pulmonary complications and respiratory failure responsible for more than 85% of deaths. Albeit the inevitability of respiratory failure and short-term death, standardized intervention protocols have been shown to significantly delay the need for invasive ventilatory support, thus prolonging survival and enhancing quality of life. The authors present an intervention protocol based on clinical progression and respiratory parameters. Decisions regarding initiation of non invasive positive pressure ventilation (NIPPV) and mechanically assisted coughing, depend on development of symptoms of hypoventilation and on objective deterioration of respiratory parameters especially in what concerns bulbar muscle function. These include maximum inspiratory capacity (MIC), difference between MIC and vital capacity (MIC-VC), and assisted peak cough flow (PCF). These standardized protocols along with patient and caregivers education, allow for improved quality of life, prolonged survival and delay or eventually prevent the need for tracheotomy and invasive ventilatory support. Supplemental oxygen should be avoided in these patients, since it precludes use of oxymetry as feedback for titrating NIPPV and MAC, and is associated with decreased ventilatory drive and aggravated hypercapnia. PMID- 17868523 TI - [Differences between SSRI's pharmacokinetics and pharmacodinamics]. AB - Selective serotonin reuptake inhibitors (SSRI) are nowadays the preferred treatment for patients with depression and anxiety disorders, when compared with traditional tricyclic antidepressants. All the SSRIs were designed to selectively potentiate serotonin [5-hydroxytryptamine (5-HT)] activity through inhibition of the 5 -HT neuronal reuptake transporter. However, despite a common mode of proven antidepressant efficacy and a similar range of indications, each SSRI has individual properties, not only pharmacodinamics, but also pharmacokinetics, which contributes for different pattern of clinical indications, side effects and interactions. The authors pretended to review the differences between each SSRI, in terms of metabolism and clinical goals. They analyzed several studies published in the last years, obtained through MedLine research. The authors describe how the unique secondary binding properties of each SSRI account for clinical significant differences in tolerability and side-effects profiles, particularly in some patients. Secondary properties within the class of SSRIs include some combinations of actions at noradrenergic, dopaminergic, muscarinic, cholinergic, histaminergic and sigma receptors. In addition, most SSRI inhibit al least one of the cytochrome P450 enzymes, resulting in potential pharmacokinetics interactions with co-prescribed drugs. PMID- 17868524 TI - [Gaucher disease]. AB - We describe, with a brief thematic review, the case of a 47-year-old woman that was hospitalized to study a clinical picture characterized by massive splenomegaly with asthenia, postprandial fullness, weight loss and edema in the left lower extremity, in which Gaucher disease was diagnosed. PMID- 17868525 TI - [Fracture of the hamate with carpometacarpal dislocation]. AB - Hamate fractures are rare injuries, frequently associated to dislocation of the ring and little fingers at the hamate-metacarpal joint. Its diagnosis is difficult, leading to delays in diagnosis. A strong clinical suspicion and appropriated radiographic exams are essential. The authors present a series of three clinical cases of fracture of the unciforme with carpometacarpal dorsal dislocation of the 4 masculine and 5 masculine fingers. For each case, they discuss the diagnosis, radiographic study, treatment and prognostic. PMID- 17868526 TI - Maxilla osseus sequestre and oral exposure: effects of the treatment of multiple myeloma with bisphosphonates. AB - Multiple myeloma, the second most common haematopoietic cancer, represents a collection of plasma-cell neoplasms that invariably become fatal when self renewing myeloma cells begin unrestrained proliferation. The major clinical manifestation of multiple myeloma is related to loss of bone through osteolysis. The bone disease can lead to pathologic fractures, spinal cord compression, hypercalcemia, and pain. It is also a major cause of morbidity and mortality in these patients. These patients frequently require radiation therapy, surgery and analgesic medications. Bisphosphonates are specific inhibitors of osteoclastic activity, and are currently used to prevent bone complications and to treat malignant hypercalcemia in patients with multiple myeloma, or bone metastases from breast and prostate cancers. Recent published reports have documented a possible link between treatment with intravenous bisphosphonates and osteonecrosis of the jaw. Bisphosphonates have been demonstrated to alter the normal bone microenvironment and appear to have direct effects on tumours as well. These changes may contribute to the development of osteonecrosis of the jaw in these patients, particularly after tooth extractions or other invasive dental procedures. Osteonecrosis of the mandible has been reported in 3 patients from Centro Hospitalar de Vila Nova de Gaia (CHVNG) with multiple myeloma treated for over 18 to 48 months with intravenous bisphosphonate zoledronate. It has been postulated that bisphosphonates may cause oral avascular bone necrosis due to antiangiogenic effect leading to disruption of osteoclast-mediated bone resorption. Although this report serves to alert clinicians about the potential complication of bone necrosis in patients receiving bisphosphonates therapy, many questions remain concerning the underlying pathogenesis of this process. In these 3 described clinical cases, surgical debridment without flap elevation, intensive antibiotherapy and zolendronate treatment arrest made possible the partial recovery of the patients. We purpose this type of clinical approach in patients suffering from multiple myeloma and bone osteonecrosis induced by bisphosphonate treatment. Research to determine the mechanism of this dental phenomenon is needed to fully validate and substantiated the possible link between bisphosphonates treatment of multiple myeloma or other cancer diseases with avascular osteonecrosis of the jaws. Until then, clinicians involved in the care of patients at risk should consider this possible complication. PMID- 17868527 TI - [Breastfeeding: prevalence and determinant factors]. AB - Breastfeeding is the best way of feeding the baby for the first six months of life. However, in Portugal the abandonment rate of breastfeeding is very high during the baby first's months of life. The aim of this study was to assess prevalence of breastfeeding and to identify related factors during the six months after delivery, as socio demographic variables and life styles. We conducted a cohort study at the Maternity of the Hospital Santa Maria. A standard questionnaire was applied to 475 women after delivery, at three and six months postpartum. We studied socio demographics aspects, life styles and the way of feeding during the six months after delivery. Multivariate analysis was performed. The women studied (mean age of 29.8 +/- 5,4 years), 52.2% were primiparous, 86.1% were Caucasian, 40% had a high school degree and 33% had a University degree. Four hundred and sixty (96.8%) received prenatal care. The mean gestational age was 38.8 +/- 2 weeks and the birth weight was 3198.3 +/- 545.3 g. At the discharge 91% were breastfeeding (77% exclusively), 54.7% at third month and 34.1% at sixth month. The main causes pointed for abandoning breastfeeding were insufficient milk production, bad sucking and return to work. The milk formula introduction was in 68.6% cases by medical recommendation. The decision in maintenance breastfeeding at third and sixth months was correlated with a previous positive breastfeed experience, high educational level, healthy lifestyles, as non-smoking, regular physical activity, and information about advantage of breastfeed for mother health. Information about breastfeeding was received by media, friends, family and only 9% by health professionals. Fifty (13%) women had no information about breastfeeding. Although breastfeeding rate at discharge was high, there was an important rate of abandonment at third and sixth month. Healthy lifestyles, high educational level, a previous positive breastfeed experience had a positive influence in breastfeeding. Understanding attitudes towards pregnancy and breastfeeding can lead to new strategies for its promotion and maintenance. PMID- 17868528 TI - [Pregnancy and smoking: an opportunity to change behaviours]. AB - INTRODUCTION: Maternal smoking during pregnancy is related not only to perinatal adverse events but also to important postnatal problems. Smoking is very prevalent in women with several socio-demographic factors playing an important role. AIMS: To assess the frequency of smoking as well as mothers' change in behaviours during pregnancy. To identify socio-demographic factors associated to smoking and to assess women's knowledge and sources of information about adverse effects of smoking during pregnancy. METHODS: We started a cohort study between March and October 2003 at the Maternity, Hospital Santa Maria. After an informed consent the mothers in the post natal ward were asked to fill in a questionnaire. RESULTS: Four hundred and seventy five mothers responded to the questionnaire and among them 30% were smokers before pregnancy. Thirty five percent stopped smoking during pregnancy and those who continued significantly reduced the number of cigarettes per day. Smoking was less prevalent in married women, with higher educational level and with stable employment (statistically significant correlations). Forty five percent of the mothers were misinformed or had no information about the adverse effects of smoking during pregnancy. Their main source of information were the media. DISCUSSION: Smoking prevalence was high (30%) among the respondents but the pregnancy lowered the numbers of cigarettes per day. The percentage of misinformed mothers concerned about the adverse effects of smoking during pregnancy was high (45%), which also showed that doctors' role as a source of information was surpassed by the media. The study also brought to light the need for the health professionals to improve their competences in their role on prevention of smoking during pregnancy and the postnatal period. PMID- 17868529 TI - [Pregnancy and physical exercise: myths, evidence and recommendations]. AB - In recent years there has been a great increase of scientific research regarding physical exercise during pregnancy. Nevertheless, many doubts persist leading to a decrease of its practice. We aimed to evaluate the main factors that influence the practice of physical activity during pregnancy and mothers' knowledge regarding its effects. Physical activity has decreased significantly, although it was higher in nulliparous mothers, with higher educational level, employment and between 25 and 34 years old. Mothers who practiced exercise during pregnancy breastfed longer. No correlation was found concerning birth weight, gestational age or obstetric pathology. Although most mothers understand the benefits of physical activity in pregnancy, that doesn't seem to translate in an increasing practice. We believe there should be an increased awareness of health professionals in order to promote controlled physical exercise in pregnant woman. PMID- 17868530 TI - [Primary prevention of allergic disease]. AB - Allergic diseases are a major public health problem. It is essential to develop prevention strategies applied to it. A number of risk factors have been identified, but some are still under contradictory. Changing the dietary pattern of the at-risk infant may prevent food allergy. Evidence suggests that exclusive breast-feeding for the first 4-months seems to protect against atopic dermatitis in infants and early childhood wheezing. Breast-feeding should be encouraged for all infants because of all its well known benefits. Hydrolyzed formulas cannot substitute breast milk on the prevention of allergic diseases. Extensively hydrolysed formulas should be encouraged as a supplement to breast milk in high risk infants whenever necessary. Partially hydrolysed formulas may be a reasonable substitute, but more studies are necessary. There is no evidence that avoiding allergenic foods during pregnancy will reduce the incidence of allergenic diseases in child. Avoidance food and aeroallergen seems effective in reducing early childhood wheeze, atopic dermatitis and asthma. Maternal avoidance of allergenic foods during lactation should only be undertaken under medical supervision by highly motivated mothers with a high risk of allergy in the offspring. PMID- 17868531 TI - [Intrapartum management strategies for congenital cervical teratoma: the EXIT procedure (ex utero intrapartum treatment)]. AB - Cervical teratomas are 3 to 5% of all teratomas and have an incidence of 1:20,000 to 1:40,000 live-borns. M.J.F., 31-years-old, had done a routine scan during pregnancy that evidenced a large fetal neck mass with teratoma cervical sonographic aspect. An interdisciplinary reunion decided for expectant management until pregnancy term when C section with EXIT procedure would be performed. At 34 weeks occurred spontaneous preterm labor and the interdisciplinary team was contacted. After head exteriorization a large neck mass was noticed. The EXIT procedure was performed allowing a tranquil orotracheal intubation while placental circulation was sustained. At third day the patient presented hypoxia, decreased heart rate and central cyanosis developing cardiorespiratory failure with unsuccessful response to resuscitation. Cervical teratoma is a rare fetal condition that is very important an interdisciplinary approach performing EXIT procedure to allow an adequate respiratory assistance at delivery. Intensive neonatal care is essential to improve patient outcome. PMID- 17868532 TI - [Neonatal lupus erythematosus]. AB - Neonatal lupus erythematosus (NLE) is a rare immune disease. Clinical findings include congenital heart block (CHB), cutaneous manifestations, and hepatic and haematological abnormalities. The authors present a case of a baby with prenatal diagnosis of bradycardia. On the first day of life, she was bradycardic and a CHB (Mobitz type II) with left branch complete block was diagnosed. She had no structural cardiac abnormalities on the scan. Spontaneous resolution of the CHB occurred and she was discharged on the seventh day of life. On the third month of life cutaneous lesions and alimental difficulties were noted. She was diagnosed a complete heart block and a definitive pacemaker was instituted with clinical improvement. Anti-Ro antibodies were positive in the mother and in the child, with the skin biopsy consistent with NLE. Heart block is usually permanent but it can spontaneously revert temporarily to sinus rhythm. A long term follow-up is essential. PMID- 17868533 TI - [Leukemoid reaction and fever after polyvalent polysaccharide pneumococcal vaccination]. AB - Streptococcus pneumoniae is one of the leading causes of pneumonia and several other invasive diseases as well as upper respiratory tract infections. They are more prevalent and serious in elderly and in those with chronic diseases and with high morbidity and mortality. Invasive pneumococcal diseases can most effectively be prevented by vaccination. The vaccine is effective and safe, even after revaccination. Nevertheless, some adverse events can occur, the most frequent being local, mild and self-limited. Although unusual, serious systemic reactions can eventually have a great impact in the individual health. The authors report a clinical case of a 66 years old man who was vaccinated with polyvalent polysaccharide pneumococcal vaccine and who developed a serious local and systemic reaction, including leukemoid reaction and respiratory insufficiency. In this respect they make some comments regarding the value of this vaccine. PMID- 17868534 TI - [Thyroid lymphoma]. AB - Thyroid Lymphomas are rare tumors among thyroid neoplasms. Almost all types originate from B cells and the most frequent subtype is a diffuse large cell lymphoma. The majority arise in a background of Hashimoto's thyroiditis and patients present with a thyroid mass, rapidly enlarging and with pressure symptoms. The treatment depends on the histological subtype and stage of the disease but include radiotherapy and/or chemotherapy. The prognosis usually is favorable. The reported case presents a thyroid lymphoma. We discussed the clinic, diagnosis and treatment. PMID- 17868535 TI - [MYH associated polyposis: severe phenotype in the homozygosity for the 1103delC mutation]. AB - MYH-associated polyposis (MAP) is an autosomal recessive disease associated with multiple colonic adenomas and colorectal cancer. Y165C and G382D MYH missense mutations are involved in more than 80% of cases in Caucasians and the large series published do not include patients homozygous for other mutations. We present the report of two siblings homozygous for the nonsense frameshift mutation 1103delC. The proband aged 28 presented with four colonic adenocarcinomas and 20-30 synchronous adenomas. Her sister aged 24 had 20 colonic adenomas and a severe Spigelman's III duodenal adenomatosis. Their parents, aged 60 and 51, heterozygous for the 1103delC MYH mutation, presented 5 and 2 low risk colorectal adenomas, respectively. PMID- 17868536 TI - Duro Armen Baglivi--homage in June. Commemorating 300th anniversary of Duro Baglivi's death. PMID- 17868537 TI - Most common inhalant allergens in atopic dermatitis, atopic dermatitis/allergic rhinitis, and atopic dermatitis/bronchial asthma patients: a five-year retrospective study. AB - Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease with a distinctive clinical appearance and distribution. Around 85% of patients have positive immediate skin reaction or specific IgE to different airborne allergens that are in association with respiratory allergy. The aim of this retrospective, open and uncontrolled study was to identify the most common inhalant allergens in AD patients, AD/allergic rhinitis patients, and AD/bronchial asthma patients by skin prick test per year during the 2001-2005 period. PMID- 17868538 TI - The role of Chlamydia trachomatis in prostatitis syndrome--our experience in diagnosis and treatment. AB - Since the beginning of 1999, over 1500 patients with symptoms of chronic prostatitis were examined at Dr. Fran Mihaljevic University Hospital for Infectious Diseases in Zagreb. In almost all of these patients urethral swabs and quantitative segmented bacteriologic cultures and microscopy of expressed prostatic secretion (EPS) or voided bladder urine3 (VB3) were performed as described by Meares and Stamey. Urethral swabs, EPS or VB3 were examined for the presence of Chlamydia (C.) trachomatis by McCoy culture and Lugol stain or by immunofluorescent typing with monoclonal antibodies. In the majority of patients C. trachomatis was demonstrated in parallel in EPS or VB3 by DNA/RNA hybridization method. Normal white blood cell count viewed per high power field<10 was found in 362 (68%) of 536 patients with symptoms of chronic prostatitis and C. trachomatis detected in EPS or VB3. These findings additionally suggest that C. trachomatis can be suspected as a causative pathogen in all categories of chronic prostatitis syndrome. Furthermore, this paper summarizes the results of five previously published clinical studies on the efficacy and tolerability of various treatment schemes for chronic chlamydial prostatitis, conducted from the beginning of 1999 until the end of 2003. PMID- 17868539 TI - A dose-finding study of azithromycin in the treatment of acne vulgaris. AB - This open, multicenter, comparative, randomized study included 120 subjects with papulopustular stage of acne vulgaris. Subjects were randomized to one of the three treatment groups (A, total dose 4.5 g of azithromycin in 7 weeks; B, total dose 6.0 g in 10 weeks; and C, total dose 7.5 g in 13 weeks). The aim was to identify the optimum azithromycin dose in the treatment of acne vulgaris through monitoring the efficacy and safety of three dosage regimens. Clinical efficacy was assessed upon completion of study therapy and six months of therapy initiation. Post-therapeutic efficacy assessment was available in 104 subjects. The difference between three treatment groups was most pronounced in the "cure" category (36.11% in group A, 58.82% in group B and 55.88% in group C) and "failure" category (8.33% in group A, and no failures in groups B and C). Follow up efficacy assessment was available in 87 subjects. The group percentage of "cure" was lower and group percentage of "treatment failure" higher in group A than in groups B and C. Azithromycin in a total dose of 6.0 g in 10 weeks seems to be a promising agent in the treatment of papulopustular acne vulgaris with few side effects and good patient compliance. PMID- 17868540 TI - Axillary apocrine carcinoma associated with apocrine adenoma and apocrine gland hyperplasia. AB - Apocrine carcinomas represent a rare group of tumors with a potential for destructive local invasion, regional and distant metastases, and are equally common in both sexes. A case of a 79-year-old woman with axillary apocrine carcinoma associated with apocrine adenoma and apocrine gland hyperplasia is presented. To our knowledge, this is the first case diagnosed in a Caucasian and also the first case diagnosed in a female patient. Grossly, the tumor measured 3.2x1.5x1.2 cm and on cut section appeared granular, white to gray-tanned. Microscopically, the tumor was located in the dermis, poorly demarcated, focally necrotic with ulcerated overlying skin. It was predominantly composed of complex, closely packed tubuloglandular structures but in few areas papillary structures were also observed. The cells contained abundant eosinophilic, finely granular cytoplasm with pleomorphic nuclei and showed apocrine-like decapitation. The cytoplasm contained periodic acid Schiff diastase resistant granules. Mitoses were frequent and some were atypical. In one area, the tumor was lobular and composed of tubular structures lined with one layer of uniform cuboidal or columnar eosinophilic cells, indicating a pre-existing apocrine adenoma. Beneath the tumor, in the deep dermis and subcutaneous tissue, hyperplastic apocrine glands were also found. No additional therapy was used, and one year after the surgery the patient was alive and showed no signs of tumor spread. This and previously reported cases suggest that apocrine hyperplasia and apocrine adenoma may represent successive steps in the development of apocrine carcinoma. PMID- 17868541 TI - Acroangiodermatitis (pseudo-Kaposi sarcoma): three case reports. AB - Acroangiodermatitis (synonym pseudo-Kaposi sarcoma) is a dermatological condition characterized by purple-colored nodules, plaques or patches, mostly on the extensor surfaces of lower extremities, usually in patients with chronic venous insufficiency and arteriovenous malformations of the legs, but also in hemodialysis patients with iatrogenic arteriovenous shunts, paralyzed limbs and amputation stumps. Acroangiodermatitis in patients with chronic venous insufficiency manifests usually as bilateral skin lesions located on the dorsa of the feet, halux and second toe, or on the medial aspect of lower legs. Acroangiodermatitis may look like Kaposi sarcoma, but in contrast to Kaposi sarcoma, acroangiodermatitis is not characterized by progression of changes, and there is a lack of spindle cells and silt-like vessels on histopathologic analysis. Three cases of acroangiodermatitis encountered in our clinical practice are described. The patients presented with livid-erythematous patches on lower legs and skin changes connected with chronic venous insufficiency, treated at the Department Phlebology Unit. Results of the histopathologic analysis indicated acroangiodermatitis. Thus, in clinical practice it is important to recognize acroangiodermatitis and to exclude Kaposi sarcoma, as sometimes there is similarity with this entity. Topical therapy with neutral and local corticosteroid preparations is often useful, however, the use of compressive bandages and dermatologic follow up are recommended. PMID- 17868542 TI - An overview on atopic dermatitis in children. AB - Atopic dermatitis (AD) is a chronic recurring inflammatory skin disease divided into at least two different forms: atopic (extrinsic) and non-atopic (intrinsic) dermatitis. Genetic epidemiological studies have unraveled several chromosomal loci with putative candidate genes, some of which are localized on chromosomes 3, 17 and 20, and most recently on 1q21. AD represents a large and continuous spectrum of one disease where different contributions from epidermal, immunologically relevant genes and their interactions with environmental signals dictate the outcome of sensitization. AD appears early in childhood and has a typical clinical picture with characteristic remissions and exacerbations. The variability of the clinical picture is related to the complex etiopathogenesis of the disease and patient's age, and is accompanied by moderate to strong itch. This review outlines recent standpoints on the etiopathogenesis, diagnosis, treatment and prevention of AD. PMID- 17868543 TI - Occupational health hazards of artists. AB - Artists may be exposed to a variety of potentially noxious materials. The modern techniques they use imply exposure to environmental hazards. Occupational health was evaluated in individuals engaged in different arts such as sculpture, painting, printmaking, restoration photography, glass-work and ceramics, because of exposure to toxic chemicals in art materials, tools and methods used in their work. This evaluation demonstrated that artists sustain extensive exposure to toxic substances similar to occupational exposure of workers in different industrial settings. Hazards for artists are numerous and therefore it is important to identify the noxious materials and techniques used. Preventive measures should include basic safety, precautions, education and preventive medical surveillance. PMID- 17868544 TI - Differential diagnosis of neonatal and infantile erythroderma. AB - Neonatal and infantile erythroderma is a diagnostic and therapeutic challenge. Numerous underlying causes have been reported. Etiologic diagnosis of erythroderma is frequently difficult to establish, and is usually delayed, due to the poor specificity of clinical and histopathologic signs. Differential diagnosis of erythroderma is a multi-step procedure that involves clinical assessment, knowledge of any relevant family history and certain laboratory investigations. Immunodeficiency must be inspected in cases of severe erythroderma with alopecia, failure to thrive, infectious complications, or evocative histologic findings. The prognosis is poor with a high mortality rate in immunodeficiency disorders and severe chronic diseases such as Netherton's syndrome. PMID- 17868545 TI - Occupational skin diseases caused by UV radiation. AB - This overview highlights the risk of skin diseases arising in workers exposed to ultraviolet radiation (UVR) at their workplace. There is a plethora of skin manifestations in outdoor workers such as seamen, fishermen, farmers after acute intense or long-term exposure to solar UVR, but some cutaneous diseases may also develop in indoor workers exposed to artificial sources. In recent years, investigations of the biological effects and damage caused by UVB and UVA on the skin have improved our understanding of the cellular and molecular mechanisms of photoaging, skin cancer and other skin diseases caused by UVR exposure. The necessity of primary prevention in workers exposed to UVR is emphasized. PMID- 17868546 TI - Teledermatology. PMID- 17868551 TI - Q fever outbreak in the Netherlands: a preliminary report. PMID- 17868550 TI - Outbreak of respiratory infection on a cruise ship. PMID- 17868552 TI - A case of trichinellosis in Denmark, imported from Poland, June 2007. PMID- 17868553 TI - Ongoing measles outbreak in Switzerland: results from November 2006 to July 2007. PMID- 17868554 TI - Use of Gamma-interferon assays in low- and medium-prevalence countries in Europe: a consensus statement of a Wolfheze Workshop organised by KNCV/EuroTB, Vilnius Sept 2006. PMID- 17868556 TI - Outbreak of Q fever among a group of high school students in Slovenia, March April 2007. PMID- 17868557 TI - Outbreak of trichinellosis in North-Western Poland--update and exported cases, June-July 2007. PMID- 17868558 TI - Importation of Polish trichinellosis cases to Ireland, June 2007. PMID- 17868559 TI - Cluster of trichinellosis cases in Germany, imported from Poland, June 2007. PMID- 17868560 TI - Outbreak of trichinellosis in North-Western Poland, June 2007. PMID- 17868561 TI - Salmonella Kottbus outbreak in infants in Gran Canaria (Spain), caused by bottled water, August-November 2006. PMID- 17868563 TI - Outbreak of acute gastroenteritis in Greece during a school excursion, April 2007. PMID- 17868564 TI - Highly pathogenic avian influenza A/H5N1 in birds within the EU--implications for public health. PMID- 17868565 TI - Drug-resistant tuberculosis: World Health Organization launches global response plan 2007-2008. PMID- 17868568 TI - Outbreak of tuberculosis in a junior school in south-eastern England. PMID- 17868569 TI - First cases of infections caused by Panton-Valentine leukocidin positive community-acquired methicillin-resistant Staphylococcus aureus in Bulgaria. PMID- 17868570 TI - Genetic evidence of Puumala and Tula Hantaviruses in rodents in the Jura region, France--preliminary results. PMID- 17868571 TI - Letter to the editor: Influenza antiviral susceptibility monitoring activities in relation to national antiviral stockpiles in Europe during the winter 2006/2007 season. PMID- 17868573 TI - A case of tetanus in a child whose parents refused immunisation--Piedmont Region, Italy, 2006. PMID- 17868574 TI - Outbreak of measles among Irish Travellers in England, March to May 2007. PMID- 17868575 TI - Outbreak of measles among Irish Travellers in Norway: an update. PMID- 17868576 TI - International outbreak of Salmonella Senftenberg in 2007. PMID- 17868577 TI - Prevalence of the new genetic variant of Chlamydia trachomatis in Sodra Alvsborg County, Vastra Gotaland Region, Sweden. PMID- 17868578 TI - Infant Staphylococcal scalded skin syndrome, Ireland, 2007--preliminary outbreak report. PMID- 17868579 TI - Measuring the impact of PCV7 in the European Union: why it is a priority. PMID- 17868581 TI - ECDC to launch first report on communicable diseases epidemiology in the European Union. PMID- 17868580 TI - Ostreopsis ovata and human health: epidemiological and clinical features of respiratory syndrome outbreaks from a two-year syndromic surveillance, 2005-06, in north-west Italy. PMID- 17868582 TI - Increase of reported HIV infections in Sweden. PMID- 17868583 TI - New International Health Regulations come into force. PMID- 17868584 TI - Avian influenza A/(H7N2) outbreak in the United Kingdom. PMID- 17868585 TI - Low Pathogenicity Avian Influenzas and human health. PMID- 17868586 TI - An outbreak of Verocytotoxin-producing Escherichia coli O26:H11 caused by beef sausage, Denmark 2007. PMID- 17868587 TI - Case report on fatal human rabies infection in Hamburg, Germany, March 2007. PMID- 17868588 TI - Terminology services--an example of knowledge management in public health. PMID- 17868589 TI - An outbreak of measles among a travelling community from England in Norway: a preliminary report. PMID- 17868590 TI - A case of native valve infective endocarditis caused by Alcaligenes xylosoxidans. PMID- 17868591 TI - EpiNorth website updated with 2006 data. PMID- 17868592 TI - New Health Communication Unit in ECDC. PMID- 17868593 TI - Monitoring HIV prevalence in blood donations in Europe. PMID- 17868594 TI - World Health Assembly adopts resolution on influenza virus sharing. PMID- 17868596 TI - First tuberculosis cases in Italy resistant to all tested drugs. PMID- 17868597 TI - Influenza vaccine coverage and the attack rate of influenza-like illness among the elderly in Portugal: is there a correlation? PMID- 17868598 TI - Large outbreak of acute gastroenteritis in Samokov Region, Bulgaria, February 2007. PMID- 17868600 TI - Influenza transmission: research needs for informing infection control policies and practice. PMID- 17868601 TI - Outbreak of measles in Geneva, Switzerland, March-April 2007. PMID- 17868602 TI - Russian-German initiative tackles infectious diseases. PMID- 17868603 TI - Clinical trial search portal launched. PMID- 17868605 TI - Significant increase of hantavirus infections in Germany since the beginning of 2007. PMID- 17868606 TI - Vibrio cholerae O1 strains with decreased susceptibility to fluoroquinolones in travellers returning from India (Rajasthan) to France, April 2007. PMID- 17868607 TI - A large outbreak of cryptosporidiosis in western Ireland linked to public water supply: a preliminary report. PMID- 17868608 TI - The current status of HPV and rotavirus vaccines in national immunisation schedules in the EU--preliminary results of a VENICE survey. PMID- 17868609 TI - Distribution of Clostridium difficile PCR ribotype 027 in British hospitals. PMID- 17868610 TI - First isolation and report of clusters of Clostridium difficile PCR 027 cases in Ireland. PMID- 17868612 TI - Large outbreak of viral gastroenteritis caused by contaminated drinking water in Apulia, Italy, May-October 2006. PMID- 17868613 TI - An ongoing outbreak of lymphogranuloma venereum in the Netherlands, 2006-2007. PMID- 17868614 TI - Sporadic human cases of cowpox in Germany. PMID- 17868615 TI - Interim H5N1 vaccine for humans approved in US. PMID- 17868616 TI - The European Network for Diagnostics of Imported Viral Diseases (ENIVD)--12 years of strengthening the laboratory diagnostic capacity in Europe. PMID- 17868617 TI - Outbreak of shigellosis in Denmark associated with imported baby corn, August 2007. PMID- 17868618 TI - Prevalence surveillance system of nosocomial infections in Norway. AB - In 1996, the Norwegian Ministry of Health issued regulations on the prevention of nosocomial infections (NIs). The regulations were revised in 2005. As part of the infection control programme, hospitals and long-term care facilities are obliged to have a surveillance system for NIs in place and to report the results to the Norwegian Institute of Public Health. PMID- 17868619 TI - WHO highlights need for collective international efforts to face emerging diseases. PMID- 17868620 TI - An outbreak of Escherichia coli O157 phage type 2 infection in Paisley, Scotland. PMID- 17868621 TI - Trichinellosis outbreak in Bavaria caused by cured sausage from Romania, January 2007. PMID- 17868622 TI - An outbreak of cryptosporidiosis at a day-care centre in Sweden. PMID- 17868623 TI - Influenza activity in the Southern Hemisphere: a preliminary look at the winter 2007 season. PMID- 17868624 TI - An outbreak of gastroenteritis in a campsite in Romania, July 2007. PMID- 17868625 TI - Salmonellosis outbreak in connection with the Formula One race, August 2007 in Hungary. PMID- 17868626 TI - European Commission launches Green Paper on bio-preparedness. PMID- 17868628 TI - The mechanism of priming: episodic retrieval or priming of pop-out? AB - Previous studies indicate that priming affects attentional processes, facilitating processes of target detection and selection on repetition trials. However, the results are so far compatible with two different attentional views that propose entirely different mechanisms to account for priming. The priming of pop-out hypothesis explains priming by feature weighting processes that lead to more frequent selections of nontarget items on switch trials. According to the episodic retrieval account, switch trials conversely lead to temporal delays in retrieving priority rules that specify the target. The results from two eye tracking experiments clearly favour the priming of pop-out hypothesis: Switching the target and nontarget features leads to more frequent selection of nontargets, without affecting the time-course of saccades to a great extent. The results from two more control experiments demonstrate that the same results can be obtained in a visual search task that allows only covert attention shifts. This indicates that eye movements can reliably indicate covert attention shifts in visual search. PMID- 17868629 TI - The development of cued versus contextual conditioning in a predictable and an unpredictable human fear conditioning preparation. AB - In this human fear conditioning study, the online development of conditioned US expectancy to discrete cues and background contexts was measured in two groups. In the paired group (n=30), the CS was systematically followed by an aversive shock (US). In the unpaired group (n=30), CS and US were presented explicitly unpaired. Using US-expectancy ratings, we replicated the basic finding already illustrated in humans with startle modulation. In the paired group, the CS elicited more US-expectancy than the context, whereas in the unpaired group, the context elicited more US-expectancy than the CS. Interestingly, we also observed a trial-by-trial development of conditioning to the context in the unpaired group as indicated by a significant linear trend. This gradual development and the evidence for the role of US-expectancy in contextual fear add to the idea that cued and contextual fear rely on the same basic associative processes. PMID- 17868630 TI - Collective rationality in interactive decisions: evidence for team reasoning. AB - Decision theory and game theory rest on a fundamental assumption that players seek to maximize their individual utilities, but in some interactive decisions it seems intuitively reasonable to aim to maximize the utility of the group of players as a whole. Such team reasoning requires collective preferences and a distinctive mode of reasoning from preferences to decisions. Findings from two experiments provide evidence for collective preferences and team reasoning. In lifelike vignettes (Experiment 1) and abstract games (Experiment 2) with certain structural properties, most players preferred team-reasoning strategies to strategies supporting unique Nash equilibria, although individually rational players should choose equilibrium strategies. These findings suggest that team reasoning predicts strategy choices more powerfully than orthodox game theory in some games. PMID- 17868631 TI - Optic disk and nerve fiber layer imaging to detect glaucoma. AB - PURPOSE: To compare optic disk and retinal nerve fiber layer (RNFL) imaging methods to discriminate eyes with early glaucoma from normal eyes. DESIGN: Retrospective, cross-sectional study. METHODS: In a tertiary care academic glaucoma center, 92 eyes of 92 subjects (46 with early perimetric open-angle glaucoma and 46 controls) were studied. Diagnostic performance of optical coherence tomography (StratusOCT; Carl Zeiss Meditec, Dublin, California, USA), scanning laser polarimetry (GDx VCC; Laser Diagnostic Technologies, San Diego, California, USA), confocal laser ophthalmoscopy (Heidelberg Retinal Tomograph [HRT] III; Heidelberg Engineering GmbH, Heidelberg, Germany), and qualitative assessment of stereoscopic optic disk photographs were compared. Outcome measures were areas under receiver operator characteristic curves (AUCs) and sensitivities at fixed specificities. Classification and regression tree (CART) analysis was used to evaluate combinations of quantitative parameters. RESULTS: The average (+/- standard deviation) visual field mean deviation for glaucomatous eyes was 4.0 +/- 2.5 dB (decibels). Parameters with largest AUCs (+/- standard error) were: average RNFL thickness for StratusOCT (0.96 +/- 0.02), nerve fiber indicator for GDx VCC (0.92 +/- 0.03), Frederick S. Mikelberg (FSM) discriminant function for HRT III (0.91 +/- 0.03), and 0.97 +/- 0.02 for disk photograph evaluation. At 95% specificity, sensitivity of disk photograph evaluation (90%) was greater than GDx VCC (P = .05) and HRT III (P = .002) results, but not significantly different than those of StratusOCT (P > .05). The combination of StratusOCT average RNFL thickness and HRT III cup-to-disk area with CART produced a sensitivity of 91% and specificity of 96%. CONCLUSIONS: StratusOCT, GDx VCC, and HRT III performed as well as, but not better than, qualitative evaluation of optic disk stereophotographs for detection of early perimetric glaucoma. The combination of StratusOCT average RNFL thickness and HRT III cup-to-disk area ratio provided a high diagnostic precision. PMID- 17868632 TI - Retinal sensitivity loss and structural disturbance in areas of capillary nonperfusion of eyes with diabetic retinopathy. AB - PURPOSE: To assess light sensitivity and morphologic changes of capillary nonperfused areas in diabetic retinopathy. DESIGN: Prospective, observational cross-sectional study. METHODS: Seventeen consecutive patients (20 eyes) with areas of capillary nonperfusion resulting from severe nonproliferative or proliferative diabetic retinopathy were included in the study. All eyes underwent fluorescent angiography and fundus-related microperimetry. Nonperfused areas of the retina were scanned with optical coherence tomography (OCT). RESULTS: In all 20 diabetic eyes, areas of capillary nonperfusion detected by fluorescein angiography were associated with the loss of retinal sensitivity. At the edges of the nonperfused area, retinal sensitivity tended to be reduced. The OCT images suggested a structural disturbance of the inner retina and high-reflectivity deposition located between the outer segments of photoreceptor and the retinal pigment epithelium corresponding to the areas of capillary nonperfusion. CONCLUSIONS: Areas of capillary nonperfusion resulting from severe nonproliferative or proliferative diabetic retinopathy show morphologic changes of the retinal structure, which may lead to a loss of sensitivity. PMID- 17868633 TI - Visual acuity testability in African-American and Hispanic children: the multi ethnic pediatric eye disease study. AB - PURPOSE: To compare the age- and gender-specific testability rates for the Amblyopia Treatment Study (ATS) HOTV visual acuity testing protocol using the electronic visual acuity (EVA) tester in African-American and Hispanic preschool children. DESIGN: Population-based, cross-sectional study. METHODS: Measurement of presenting monocular distance visual acuity using the ATS HOTV protocol was attempted in all African-American and Hispanic children aged 30 to 72 months from the population-based Multi-Ethnic Pediatric Eye Disease Study (MEPEDS). Children able to be tested monocularly in both eyes were considered able. Age-, gender-, and ethnicity-specific testability rates were calculated. Comparisons of testability among different groups were performed using Chi-square analyses and the Cochran trend test. RESULTS: Testing was attempted on 3,126 children (1,471 African-American, 1,655 Hispanic; 50% female). Overall, 84% (83% African American, 85% Hispanic; 86% female, 82% male) were testable. Older children were more likely to complete testing successfully than younger children (P < .0001). Age-specific testability in children 30 to 36 months of age, 37 to 48 months of age, 49 to 60 months of age, and 61 to 72 months of age was 39%, 84%, 98%, and 100%, respectively. After stratifying by age, there were no ethnicity-related differences in children testable (P = .12). Girls (86%) were slightly more likely to be testable than boys (82%; P > .003). CONCLUSIONS: Monocular threshold visual acuity testing using the ATS HOTV protocol on the EVA tester (Jaeb Center for Health Research, Tampa, Florida, USA) can be completed by most African-American and Hispanic preschool children, particularly those older than 36 months of age. This protocol therefore may be used in minority preschool children as an integral part of the diagnosis and management of amblyopia and other forms of visual impairment. PMID- 17868634 TI - A homogeneous cellular histone deacetylase assay suitable for compound profiling and robotic screening. AB - Most cellular assays that quantify the efficacy of histone deacetylase (HDAC) inhibitors measure hyperacetylation of core histone proteins H3 and H4. Here we describe a new approach, directly measuring cellular HDAC enzymatic activity using the substrate Boc-K(Ac)-7-amino-4-methylcoumarin (AMC). After penetration into HeLa cervical carcinoma or K562 chronic myeloid leukemia cells, the deacetylated product Boc-K-AMC is formed which, after cell lysis, is cleaved by trypsin, finally releasing the fluorophor AMC. The cellular potency of suberoylanilide hydroxamic acid, LBH589, trichostatin A, and MS275 as well-known HDAC inhibitors was determined using this assay. IC(50) values derived from concentration-effect curves correlated well with EC(50) values derived from a cellomics array scan histone H3 hyperacetylation assay. The cellular HDAC activity assay was adapted to a homogeneous format, fully compatible with robotic screening. Concentration-effect curves generated on a Tecan Genesis Freedom workstation were highly reproducible with a signal-to-noise ratio of 5.7 and a Z' factor of 0.88, indicating a very robust assay. Finally, a HDAC-inhibitor focused library was profiled in a medium-throughput screening campaign. Inhibition of cellular HDAC activity correlated well with cytotoxicity and histone H3 hyperacetylation in HeLa cells and with inhibition of human recombinant HDAC1 in a biochemical assay. Thus, by using Boc-K(Ac)-AMC as a cell-permeable HDAC substrate, the activity of various protein lysine-specific deacetylases including HDAC1-containing complexes is measurable in intact cells in a simple and homogeneous manner. PMID- 17868635 TI - Continuous-flow microfluidic printing of proteins for array-based applications including surface plasmon resonance imaging. AB - Arraying proteins is often more challenging than creating oligonucleotide arrays. Protein concentration and purity can severely limit the capacity of spots created by traditional pin and ink jet printing techniques. To improve protein printing methods, we have developed a three-dimensional microfluidic system to deposit protein samples within discrete spots (250-microm squares) on a target surface. Our current technology produces a 48-spot array within a 0.5 x 1 cm target area. A chief advantage of this method is that samples may be introduced in continuous flow, which makes it possible to expose each spot to a larger volume of sample than would be possible with standard printing methods. Using Biacore Flexchip (Biacore AB) surface plasmon resonance array-based biosensor as a chip reader, we demonstrate that the microfluidic printer is capable of spotting proteins that are dilute (<0.1 microg/ml) and contain high concentrations of contaminating protein (>10,000-fold molar excess). We also show that the spots created by the microfluidic printer are more uniform and have better-defined borders than what can be achieved with pin printing. The ability to readily print proteins using continuous flow will help expand the application of protein arrays. PMID- 17868636 TI - An automated, high-throughput sequence read classification pipeline for preliminary genome characterization. AB - In the absence of a complete genome sequence, considerable insight into genome structure can be gained from survey sequencing of genomic DNA. To facilitate high throughput characterization of genome structure based on shotgun sequence reads, we have developed an automated sequence read classification pipeline (SRCP). The SRCP uses a battery of novel and standard sequence analysis algorithms along with a sophisticated decision tree to place reads into "best fit" functional/descriptive categories. Once "primed" with genomic sequence data, the SRCP also permits estimation of gene/repeat enrichment afforded by reduced representation sequencing techniques. To our knowledge, the SRCP is the only tool that has been designed to provide a description of a genome or a genome component based on sample sequence reads. In an initial test of the SRCP using sequence data from Sorghum bicolor, it was shown to provide results similar in quality to results generated by manual classification. Although the SRCP is not a replacement for manual sequence characterization, it can provide a rapid, high quality overview of genome sequence content and facilitate subsequent annotation. The SRCP presumably can be adapted for analysis of any eukaryotic genome. PMID- 17868637 TI - Myeloperoxidase-catalyzed taurine chlorination: initial versus equilibrium rate. AB - Myeloperoxidase (MPO) catalyzes the two-electron oxidation of chloride, thereby producing hypochlorous acid (HOCl). Taurine (2-aminoethane-sulfonic acid, Tau) is thought to act as a trap of HOCl forming the long-lived oxidant monochlorotaurine [(N-Cl)-Tau], which participates in pathogen defense. Here, we amend and extend previous studies by following initial and equilibrium rate of formation of (N-Cl) Tau mediated by MPO at pH 4.0-7.0, varying H(2)O(2) concentration. Initial rate studies show no saturation of the active site under assay conditions (i.e. [H(2)O(2)] > or = 2000 [MPO]). Deceleration of Tau chlorination under equilibrium is quantitatively described by the redox equilibrium established by H(2)O(2) mediated reduction of compound I to compound II. At equilibrium regime the maximum chlorination rate is obtained at [H(2)O(2)] and pH values around 0.4mM and pH 5. The proposed mechanism includes known acid-base and binding equilibria taking place at the working conditions. Kinetic data ruled out the currently accepted mechanism in which a proton participates in the molecular step (MPO I+Cl(-)) leading to the formation of the chlorinating agent. Results support the formation of a chlorinating compound I-Cl(-) complex (MPO-I-Cl) and/or of ClO(-), through the former or even independently of it. ClO(-) diffuses away and rapidly protonates to HOCl outside the heme pocket. Smaller substrates will be chlorinated inside the enzyme by MPO-I-Cl and outside by HOCl, whereas bulkier ones can only react with the latter. PMID- 17868638 TI - Identification of calpastatin and mu-calpain and studies of their association in pulmonary smooth muscle mitochondria. AB - Using calpastatin antibody we have identified a 145 kDa major band along with two relatively minor bands at 120 kDa and 110 kDa calpastatin molecules in bovine pulmonary artery smooth muscle mitochondria. To the best of our knowledge this is first report regarding the identification of calpastatin in mitochondria. We also demonstrated the presence of micro-calpain in the mitochondria by immunoblot and casein zymogram studies. Immunoblot studies identified two major bands corresponding to the 80 kDa large and the 28 kDa small subunit of mu-calpain. Additionally 76 kDa, 40 kDa and 18 kDa immunoreactive bands have also been detected. Purification and N-terminal amino acid sequence analysis of the identified proteins confirmed their identity as mu-calpain and calpastatins. Immunoprecipitation study revealed molecular association between mu-calpain and calpastatin in the mitochondria indicating that calpastatin could play an important role in preventing uncontrolled activity of mu-calpain which otherwise may facilitate pulmonary hypertension, smooth muscle proliferation and apoptosis. PMID- 17868639 TI - Regulation of HAS expression in human synovial lining cells of TMJ by IL-1beta. AB - Hyaluronan (HA), a major glycosaminoglycan of synovial fluid, is synthesised by a class of membrane-bound HA synthase (HAS) proteins. In the present study, we investigated the regulatory roles of IL-1beta on HAS gene expression and HA production by the fibroblastic synovial lining cells. The synovial lining cells from synovial membrane in human temporomandibular joint (TMJ) were cultured and characterised using immunocytochemistry with CD14, CD44, and vimentin monoclonal antibodies. With or without treatment with IL-1beta, the production of HA was detected with radiometric assay and the expression of HAS mRNAs were analysed with a semi-quantitative reverse transcribed polymerase chain reaction (RT-PCR). HA synthesis was significantly augmented with 1ng/ml of IL-1beta for both 24 and 48h stimulation, however the production of HA declined if stimulated with 10ng/ml of IL-1beta. The expression of HAS2 and 3 mRNA were enhanced about 4.2- and 7.2 fold after 4h stimulation with 1ng/ml of IL-1beta, respectively. From these results, it is concluded that IL-1beta functions on regulating HAS expression and consequently promoting the secretion of HA in synovial lining cells from TMJ. PMID- 17868640 TI - Social anxiety and interpretation biases for facial displays of emotion: emotion detection and ratings of social cost. AB - The current study assessed the processing of facial displays of emotion (Happy, Disgust, and Neutral) of varying emotional intensities in participants with high vs. low social anxiety. Use of facial expressions of varying intensities allowed for strong external validity and a fine-grained analysis of interpretation biases. Sensitivity to perceiving negative evaluation in faces (i.e., emotion detection) was assessed at both long (unlimited) and brief (60 ms) stimulus durations. In addition, ratings of perceived social cost were made indicating what participants judged it would be like to have a social interaction with a person exhibiting the stimulus emotion. Results suggest that high social anxiety participants did not demonstrate biases in their sensitivity to perceiving negative evaluation (i.e. disgust) in facial expressions. However, high social anxiety participants did estimate the perceived cost of interacting with someone showing disgust to be significantly greater than low social anxiety participants, regardless of the intensity of the disgust expression. These results are consistent with a specific type of interpretation bias in which participants with social anxiety have elevated ratings of the social cost of interacting with individuals displaying negative evaluation. PMID- 17868641 TI - Hoarding in a compulsive buying sample. AB - Previous research has indicated that many compulsive buyers also suffer from compulsive hoarding. The present work specifically examined hoarding in a compulsive buying sample. Sixty-six treatment-seeking compulsive buyers were assessed prior to entering a group therapy for compulsive buying using the Compulsive Buying Scale (CBS), the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) Shopping Version, the Compulsive Acquisition Scale (CAS), the German-CBS, the Saving Inventory-Revised (SI-R), the Maudsley Obsessive Compulsive Inventory (MOCI), the Barratt Impulsiveness Scale (BIS-11), and the Structured Clinical Interview for DSM-IV Axis I (SCID). Inclusion criteria were current problems with compulsive buying according to the proposed diagnostic criteria for compulsive buying by McElroy, Keck, Pope, Smith, and Strakowski [(1994). Compulsive buying: A report of 20 cases. Journal of Clinical Psychiatry, 55, 242-248]. Our results support the assumption that many but not all compulsive buyers suffer from compulsive hoarding. A significant association between the SI-R and the compulsive buying measures CBS, Y-BOCS-SV, German-CBS, and the CAS-Buy subscale was found, which is mostly caused by the SI-R subscale acquisition. The SI-R subscales clutter and difficulty discarding were more closely associated with the CAS-Free subscale and with obsessive-compulsive symptoms. Hoarding compulsive buyers reported more severe buying symptoms and obsessive-compulsive symptoms and presented with a higher psychiatric co-morbidity, especially any current affective, anxiety and eating disorder. Specific therapeutic interventions for compulsive buyers who also report compulsive hoarding appear indicated. PMID- 17868642 TI - Confidence in memory and other cognitive processes in obsessive-compulsive disorder. AB - Previous studies have implicated beliefs about one's memory (i.e., meta-memory), in maintaining the symptoms of obsessive-compulsive disorder (OCD), particularly with respect to checking rituals. However, most research has focused on task- or situation-specific perceptions about memory performance. Expanding on this research, we undertook two studies with analogue and clinical cohorts to examine the relationship between general 'trait' beliefs about memory and related processes and OCD symptoms. Trait meta-memory as measured in the current study was conceptualised as a multi-dimensional construct encompassing a range of beliefs about memory and related processes including confidence in one's general memory abilities, decision-making abilities, concentration and attention, as well as perfectionistic standards regarding one's memory. Meta-memory factors were associated with OCD symptoms, predicting OCD symptoms over-and-above mood and other OCD-relevant cognitions. Meta-memory factors were found to be particularly relevant to checking symptoms. Implications for theory and research are discussed. PMID- 17868643 TI - Chromatin opening is tightly linked to enhancer activation at the kappa light chain locus. AB - Enhancers play an important role in chromatin opening but the temporal relationship between enhancer activation and the generation of an accessible chromatin structure is poorly defined. Recombination enhancers are essential for chromatin opening and subsequent V(D)J recombination at immunoglobulin loci. In mice, the kappa light chain locus displays an open chromatin structure before the lambda locus yet the same proteins, PU.1/PIP, trigger full enhancer activation of both loci. Using primary B cells isolated from distinct developmental stages and an improved method to quantitatively determine hypersensitive site formation, we find the kappa and lambda recombination enhancers become fully hypersensitive soon after transition to large and small pre-B-II cells, respectively. This correlates strictly with the stages at which these loci are activated. Since these cells are short-lived, these data imply that there is a close temporal relationship between full enhancer hypersensitive site formation and locus chromatin opening. PMID- 17868645 TI - Modulation of human Kv1.5 channel kinetics by N-cadherin. AB - Kv1.5 is expressed in multiple tissues including heart, brain, macrophages, as well as vascular, airway, and intestinal smooth muscle cells. Kv1.5 currents contribute to cardiac repolarization. In cardiac myocytes Kv1.5 colocalizes with N-cadherin. As Kv1.5 expression increases following establishment of cell-cell contacts and N-cadherin influences the activity of other ion channels, we explored whether N-cadherin participates in the regulation of Kv1.5 activity. To this end, we expressed Kv1.5 in Xenopus oocytes with or without additional expression of N-cadherin. Coexpression of N-cadherin was followed by a approximately 2- to 3-fold increase of Kv1.5 induced current. The effect of N cadherin was not paralleled by significant alterations of Kv1.5 channel abundance within the oocyte cell membrane but resulted primarily from accelerated recovery from inactivation. In conclusion, N-cadherin modifies Kv1.5 channel activity and is thus a novel candidate signaling molecule participating in the regulation of a variety of functions including cardiac action potential and vascular tone. PMID- 17868644 TI - Effects of triglyceride on ER stress and insulin resistance. AB - This study was conducted to examine the mechanism by which triglyceride induces insulin resistance and ER stress in HepG2 cells. Using in vitro study models, we show that triglyceride causes insulin resistance through serine phosphorylation of insulin receptor substrate-1 (IRS-1). In addition, triglyceride induces the expression of endogenous endoplasmic reticulum (ER) stress markers, including GRP 78, IRE-1alpha, XBP-1, p-eIF2alpha, CHOP, and p-JNK. ER stress, in turn, leads to the suppression of insulin receptor signaling through tyrosine dephosphorylation of IRS-1. The results of this study show that triglyceride is a central feature of peripheral insulin resistance, and also suggest that triglyceride-induced ER stress influences insulin resistance. These experiments may be used in the development of an in vitro acute obesity model. PMID- 17868646 TI - DNA damage induced by novel demethylcantharidin-integrated platinum anticancer complexes. AB - Oxaliplatin is a third generation platinum (Pt) drug with a diaminocyclohexane (DACH) entity, which has recently obtained worldwide approval for the clinical treatment of colon cancer, and apparently operates by a different mechanism of action to the classical cisplatin or carboplatin. Introducing a novel dual mechanism of action is one approach in designing a new platinum-based anticancer agent, whereby an appropriate ligand, such as demethylcantharidin (DMC), is released from the parent compound to exert a cytotoxic effect, in addition to that of the DNA-alkylating function of the platinum moiety. To investigate the likelihood of a novel dual mechanism of anticancer action, demethylcantharidin integrated Pt complexes: Pt(R,R-DACH)(DMC) with the same Pt-DACH moiety as oxaliplatin, and Pt(NH(3))(2)(DMC) akin to carboplatin; were studied for their ability to induce DNA damage in HCT116 colorectal cancer cells by an alkaline comet assay. The results showed that the DMC ligand released from the novel complexes caused additional DNA lesions when compared with oxaliplatin and carboplatin. The comet assay also revealed that the DNA-damaging behavior of cisplatin is characteristically different; and this study is the first to demonstrate the ability of DMC to induce DNA lesions, thus providing sufficient evidence to explain the superior antiproliferative effect of the novel DMC integrated complexes. PMID- 17868647 TI - cAMP-induced expression of ABCA1 is associated with MAP-kinase-pathway activation. AB - Several lines of evidence suggest that the ATP binding cassette A1 (ABCA1) is also involved in other degenerative processes such as brain neurodegeneration. Cholesterol and cAMP activate ABCA1 in a cell-specific manner. We employed a cell culture model of murine monocytes (P388) and neuroblastoma cells (N2A) and studied the differential induction of the ABCA1-gene product by modifying the cholesterol acceptor and by inhibition of the MAP-kinase pathway. Our study reveals a rise of ABCA1-expression in both N2A and P388 by cAMP. This increase is accompanied by a higher activation of the MAP-kinase-pathway. The inhibition of the MAP-kinase activation disrupts the stimulating effect of cAMP but increases the base line expression of ABCA1. Our data suggest a negative feedback between the MAP-kinase-system and ABCA1. We conclude that the interaction of the MAP kinase pathway and the ABCA1 system might affect the function of neuronal and microglial cells in the brain. PMID- 17868648 TI - Effects of high glucose on mesenchymal stem cell proliferation and differentiation. AB - High glucose (HG) concentrations impair cellular functions and induce apoptosis. Exposition of mesenchymal stem cells (MSC) to HG was reported to reduce colony forming activity and induce premature senescence. We characterized the effects of HG on human MSC in vitro using telomerase-immortalized MSC (hMSC-TERT) and primary MSC (hMSC). HG (25mM) enhanced hMSC-TERT proliferation in long-term studies in contrast to hMSC where proliferation was unchanged. Thioredoxin interacting protein, which is involved in apoptosis regulation, was stimulated by glucose in hMSC-TERT. However, apoptosis was not influenced by HG in both cell types. MSC treatment with HG favored osteogenic differentiation. MSC are resistant to HG toxicity, depending on the stemness of MSC. Proliferation and osteogenic differentiation are stimulated by HG. Effects of HG on the transient amplifying compartment of MSC may differ from those in mature cells. Further research is needed to unravel the molecular mechanisms of HG resistance of MSC. PMID- 17868649 TI - Resveratrol-induced apoptosis in human T-cell acute lymphoblastic leukaemia MOLT 4 cells. AB - Resveratrol (RES) is a natural occurring phytoalexin that has been shown to have chemopreventive activity. Resveratrol acts both by suppressing cell proliferation and inducing apoptosis in a variety of cancer cell lines. In this study, we show that RES induces apoptosis in MOLT-4 acute lymphoblastic leukaemia cells by modulating three different pathways that regulate cells survival and cell death. We show for the first time that RES inhibits the survival signalling pathways Notch and their down stream effector and modulates the operation of interacting signalling systems. It induces an increase in the levels of the pro-apoptotic proteins p53, its effector p21waf and Bax. We also show that RES inhibits the PI3K/Akt pathway and activates Gsk-3beta. The data presented here demonstrate unequivocally that RES induces apoptosis by inhibiting the Notch pathway and markedly influencing the operation of the interacting apoptosis pathways mediated by p53 and PI3K/Akt. These data support findings from other laboratories that have suggested the use of RES as a chemopreventive agent. Here, we have identified potential signalling pathways influenced by RES and this could lead to the identification of the targets of RES-induced apoptosis and growth control. PMID- 17868650 TI - Sulfated polymannuroguluronate, a novel anti-AIDS drug candidate, inhibits HIV-1 Tat-induced angiogenesis in Kaposi's sarcoma cells. AB - Kaposi's sarcoma (KS), a neoplasm often associated with iatrogenic and acquired immunosuppression, is characterized by prominent angiogenesis. Angiogenic factors released from KS and host cells and HIV viral products-the protein Tat are reported to be involved in angiogenesis. Mounting evidence further suggests that multiple angiogenic activities of Tat contribute to AIDS-associated Kaposi's sarcoma (AIDS-KS). Herein, we report that sulfated polymannuroguluronate (SPMG), a novel anti-AIDS drug candidate now undergoing phase II clinical trial, significantly eliminated Tat-induced angiogenesis in SLK cells both in vitro and in vivo. SPMG significantly and dose-dependently inhibits proliferation, migration, and tube formation by SLK cells. SPMG also dramatically arrested Tat driven KDR phosphorylation and blocked the interaction between Tat and integrin beta1, thus inhibiting the phosphorylation of the downstream kinases of FAK, paxillin and MAPKs. In addition, SPMG was noted to block the release of bFGF and VEGF from ECM. All these collectively favor an issue that SPMG functions as a promising therapeutic against Tat-induced angiogenesis and pathologic events relevant to AIDS-KS, which adds novel mechanistic profiling to the anti-AIDS action of SPMG. PMID- 17868651 TI - Sex-dependent expression of CYP2C11 in spleen, thymus and bone marrow regulated by growth hormone. AB - CYP2C11, the most commonly expressed isoform of cytochrome P450 in male rat liver, was measured in spleen, thymus and bone marrow by quantitative real-time PCR and enhanced Western blotting. CYP2C11 concentrations in the lymphoid tissues were a fraction of that observed in liver, but like the liver, were sexually dimorphic (M>F) with mRNA and protein levels in agreement. Although the response to hypophysectomy varied according to tissue and sex, expression levels of CYP2C11 in all measured tissues remained greater in males. Further differences in CYP2C11 expression between liver and lymphoid tissue were observed following restoration of the circulating masculine growth hormone profile in hypophysectomized rats. In contrast to the liver where the renaturalized growth hormone profile elevated CYP2C11 expression in both sexes, the response was opposite in spleen and thymus with isoform concentrations declining in both sexes. Lastly, the divergent response of CYP2C11 between the liver and immune system was examined in cultured splenocytes exposed to different mitogens. In contrast to the dramatic depletion of CYP2C11 reported in proliferating hepatocytes, mitogen-stimulation resulted in a significant elevation in splenocyte CYP2C11 expression. In summary, we report for the first time that thymus, spleen and bone marrow express, albeit nominal, sex-dependent levels of CYP2C11 (M>F) whose regulation appears to be under some hormonal control, but very different from that of the hepatic isoform. PMID- 17868652 TI - The interplay between viruses and innate immune signaling: recent insights and therapeutic opportunities. AB - The immediate response to viral infection relies on pattern-recognition receptors (PRRs), most prominently the Toll-like receptors (TLRs) and the RNA helicases RIG I and MDA5, as well as double stranded RNA-dependent protein kinase (PKR) and the DNA receptor, DAI. These PRRs recognize pathogen-associated molecular patterns (PAMPs) such as viral proteins and nucleic acids. The engagement of these receptors then initiates intracellular signaling cascades which ultimately cause the activation of transcription factors and the expression of type I interferons and pro-inflammatory cytokines. This innate response establishes an anti-viral state in the infected cell and its neighbours and alerts immune cells to the danger. In order to establish a productive infection, viruses need to overcome this initial anti-viral response. Evasion of innate immune defences is achieved by means of viral proteins that inhibit the signaling cascades emanating from the PRRs. The same innate signal transduction pathways have been implicated in conditions of sterile inflammation, such as rheumatoid arthritis and multiple sclerosis, and in autoimmunity. Because viral proteins target crucial host proteins involved in these pathways, they can point the way to key drug targets. Further, the viral proteins themselves or derivatives of them may be of use therapeutically to curtail inflammation and autoimmunity. PMID- 17868653 TI - Bupropion inhibits the cellular effects of nicotine in the ventral tegmental area. AB - Each year, tobacco use causes over 4 million deaths worldwide and billions of dollars are spent on treatment for tobacco-related illness. Bupropion, an atypical antidepressant, improves the rates of successful smoking cessation, however, the mechanisms by which bupropion reduces cigarette smoking and depression are unknown. Here we show that clinical concentrations of bupropion inhibit nicotine's stimulatory effects on brain reward areas. Many drugs of abuse, including nicotine, stimulate dopamine (DA) release in the mesoaccumbens reward system. Nicotinic acetylcholine receptors in the ventral tegmental area (VTA) mediate nicotine's stimulation of DA release, as well as its rewarding effects. Nicotinic receptors are expressed by excitatory and inhibitory neurons that control DA neuron excitability, and by the DA neurons themselves. Bupropion is a broad-spectrum non-competitive nicotinic receptor antagonist. Here we report that pre-treatment of brain slices with a clinically relevant concentration of bupropion dramatically reduces the effects of nicotine on DA neuron excitability. Nicotinic receptors on VTA DA neurons and their synaptic inputs are inhibited by 75 - 95% after bupropion treatment. We also find that bupropion alone reduces GABAergic transmission to DA neurons, thereby diminishing tonic inhibition of these neurons. This increases DA neuron excitability during bupropion treatment in the absence of nicotine, and may contribute to bupropion's antidepressant actions. PMID- 17868654 TI - Low blood lead levels associated with clinically diagnosed attention deficit/hyperactivity disorder and mediated by weak cognitive control. AB - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and low-level lead exposure are high-prevalence conditions among children, and studies of large populations have suggested that these conditions are related. We examine this relationship in children from a community sample exposed to average background levels of lead who have a diagnosis of ADHD that is established by clinical criteria. METHODS: One hundred fifty children ages 8-17 years participated (mean age = 14 years; 53 control subjects, 47 ADHD Predominantly Inattentive type, 50 ADHD-Combined type). Diagnosis was formally established with a semi-structured clinical interview and parent and teacher ratings. Children completed intelligence quotient (IQ) measures and the stop task (a neuropsychological measure). Lead was assayed from whole blood with inductively coupled plasma mass spectrometry. RESULTS: Blood lead levels in this sample closely matched US population exposure averages, with a maximum level of 3.4 mug/dL. Blood lead levels were statistically significantly higher in ADHD-combined type than in non ADHD control (p < .05) children. Blood lead was associated with symptoms of hyperactivity-impulsivity but not inattention-disorganization, after control of covariates. Blood lead levels were linked with a lower IQ (p < .05), but IQ did not account for effects on hyperactivity. Instead, hyperactivity mediated effects of lead on IQ. Effects of blood lead on hyperactivity-impulsivity were mediated by poor performance on the stop task. This mediation effect was independent of effects of lead on IQ. CONCLUSIONS: Low-level lead exposure might be an important contributor to ADHD. Its effects seem to be mediated by less effective cognitive control, consistent with a route of influence via striatal-frontal neural circuits. PMID- 17868655 TI - Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. AB - BACKGROUND: Prazosin, a central nervous system (CNS) active alpha-1 adrenoreceptor antagonist, has reduced nightmares and sleep disturbance in placebo-controlled studies of combat-related posttraumatic stress disorder (PTSD). We evaluated objective sleep parameters and PTSD symptoms in a placebo controlled prazosin trial for civilian trauma-related PTSD. METHODS: Thirteen outpatients with chronic civilian trauma PTSD, frequent nightmares, and sleep disturbance participated in a randomized placebo-controlled crossover trial of prazosin. Sleep parameters were quantified at home with the REMView (Respironics, Pittsburgh, Pennsylvania). The PTSD symptoms were quantified with the Clinician Administered PTSD Scale (CAPS) "recurrent distressing dreams" and "disturbed sleep" items, a non-nightmare distressed awakenings scale, the PTSD Dream Rating Scale (PDRS), the PTSD Checklist-Civilian (PCL-C), and the Clinical Global Impression of Improvement (CGI-I). RESULTS: Prazosin compared with placebo significantly increased total sleep time by 94 min; increased rapid eye movement (REM) sleep time and mean REM period duration without altering sleep onset latency; significantly reduced trauma-related nightmares, distressed awakenings, and total PCL scores; significantly improved CGI-I scores; and changed PDRS scores toward normal dreaming. CONCLUSIONS: Prazosin reductions of nighttime PTSD symptoms in civilian trauma PTSD are accompanied by increased total sleep time, REM sleep time, and mean REM period duration in the absence of a sedative-like effect on sleep onset latency. PMID- 17868656 TI - Effect of prenatal exposure to diclofenac sodium on Purkinje cell numbers in rat cerebellum: a stereological study. AB - Diclofenac sodium (DS) is commonly used as a non-steroidal anti-inflammatory drug. Although several adverse effects are clearly established, it is still unknown whether prenatal exposure to DS has an effect on the development of the cerebellum. In this study, we investigated the total number of Purkinje cells of the cerebellum in a control group and in a DS-treated group of male rats using a stereological method. The DS in a dose of 1 mg/kg daily was intraperitoneally injected to the drug-treated group of pregnant rats beginning from the 5th day after mating for a period of 15 days during pregnancy. Physiological serum at 1 ml dose was intraperitoneally injected to the control group of pregnant rats at the same period. After delivery, male offspring were obtained and each main group was divided into two subgroups that were 4-week-old (4W-old) and 20-week-old (20W old). Our results showed that the total number of Purkinje cells in offspring of drug-treated rats was significantly lower than in the offspring of control animals. These results suggest that the Purkinje cells of a developing cerebellum may be affected by administration of DS during the prenatal period. PMID- 17868657 TI - Comparative expression of p2x receptors and ecto-nucleoside triphosphate diphosphohydrolase 3 in hypocretin and sensory neurons in zebrafish. AB - The hypocretin/orexin (HCRT/ORX) excitatory neuropeptides are expressed in a small population of lateral hypothalamic cells in mammals and fish. In humans, loss of these cells causes the sleep disorder narcolepsy. Identification of genes expressed in HCRT-producing cells may be revealing as to the regulation of sleep and the pathophysiology of narcolepsy. In this study, in situ hybridization analyses were performed to characterize the expression pattern of receptors and enzyme, which regulate ATP-mediated transmission in hypocretin cells of zebrafish larvae. The zebrafish cDNA encoding the ecto-nucleoside triphosphate diphosphohydrolase 3 (ENTPD3/NTPDase3) was isolated. This transcript was found to be expressed in zebrafish HCRT cells as previously reported in mammals. It was also expressed in the cranial nerves (gV, gVII, gIV and gX) and in primary sensory neurons (i.e., Rohon-Beard neurons) in the spinal cord. The expression of known zebrafish p2rx purinergic receptor family members was next studied and found to overlap with the entpd3 expression pattern. Specifically, p2rx2, p2rx3.1, p2rx3.2 and p2rx8 were expressed in the trigeminal ganglia and subsets of Rohon-Beard neurons. In contrast to mammals, p2rx2 was not expressed in HCRT cells; rather, p2rx8 was expressed with entpd3 in this hypothalamic region. The conservation of expression of these genes in HCRT cells and sensory neurons across vertebrates suggests an important role for ATP mediated transmission in the regulation of sleep and the processing of sensory inputs. PMID- 17868658 TI - The steroid sulfatase inhibitor COUMATE attenuates rather than enhances access of dehydroepiandrosterone sulfate to the brain in the mouse. AB - Intraperitoneal injection of adult male mice with the neuroactive steroid dehydroepiandrosterone sulfate (DHEAS) at 1 and 40 mg/kg caused dose-dependent increases in the concentration of both this compound and its corresponding free steroid DHEA in brain within 1 h of injection. Pretreatment of these animals for 24 h with the steroid sulfatase inhibitor COUMATE at a dose (10 mg/kg, p.o.) shown previously to cause almost complete inhibition of this enzyme in liver and brain was expected to increase the amount of the DHEAS dose reaching the brain. Surprisingly however, the increases in brain concentrations of DHEAS and DHEA after injection of DHEAS i.p. were attenuated by pretreatment with COUMATE. The results suggest that the arylsulfamate based steroid sulfatase inhibitors such as COUMATE interfere with the influx of the DHEAS anion into the brain. PMID- 17868659 TI - Aquaporin 1 and aquaporin 4 overexpression in bovine spongiform encephalopathy in a transgenic murine model and in cattle field cases. AB - Aquaporins (AQP) are a family of transmembrane proteins that act as water selective channels. AQP1 and AQP4 are widely expressed in the central nervous system where they play several roles. Overexpression of AQP has been reported in some human and animal transmissible spongiform encephalopathies, but information is scanty about their distribution in the central nervous system in bovine spongiform encephalopathy (BSE). Double immunohistochemistry for AQP1, AQP4 and GFAP was developed in a transgenic mouse line overexpressing the bovine cellular prion protein (BoTg110), intracerebrally infected with cattle BSE. Western blot for AQP1 and AQP4, and immunohistochemistry for both AQP and GFAP were carried out in cases of BSE-diagnosed cattle as part of surveillance plan in Catalonia (Spain). A marked increase in AQP1 and AQP4 was observed in mice at the terminal stage of the disease, when they had a wide range of clinical signs, whereas no increase could be observed in the early stage before the onset of the clinical signs. In cattle which did not show evidence of clinical signs, both AQP already showed a great increase. The AQP overexpression correlated with GFAP immunoreactive astrocytes and PrPres deposition in both cases. The results of this study suggest that AQP overexpression in glial cells could lead to an imbalance in water and ion homeostasis which could contribute to triggering the typical histopathological changes of BSE. PMID- 17868660 TI - Separation of proteins including metallothionein in cerebrospinal fluid by size exclusion HPLC and determination of trace elements by HR-ICP-MS. AB - A method to study the protein binding patterns of trace elements in human cerebrospinal fluid (CSF) is described. Proteins in CSF samples were separated by size exclusion chromatography combined with high performance liquid chromatography (SEC-HPLC). The column was calibrated to separate proteins in the molecular weight range 6-70 kDa. Fractions were then analyzed off-line for trace elements using high resolution inductively coupled plasma mass spectrometry (HR ICP-MS). We were able to accurately determine more than 10 elements of clinical interest in the CSF fractions. Results are presented for Cd, Mn, Fe, Pb, Cu and Zn. The total concentrations of 16 trace elements in human plasma and CSF are also presented. The method was able to differentiate the relative contribution of metallothionein and other proteins towards metal binding in human CSF. PMID- 17868661 TI - NMR characterization of the structure of a beta-(1-->3)-D-glucan isolate from cultured fruit bodies of Sparassis crispa. AB - SCG, a purified beta-d-glucan, obtained from Sparassis crispa, exhibits various biological activities including an antitumor effect, enhancement of the hematopoietic response in cyclophosphamide-induced leukopenic mice, and induction of the production of cytokines. The mechanisms of these effects have been extensively investigated; however, an unambiguous structural characterization of SCG is yet to be achieved. It is well accepted that the biological effects of beta-glucan depend on its primary structures, conformation, and molecular weight. In the present study, we examine the difference of biological effects among beta glucans, elucidate the primary structure of SCG, and compare with SPG from Schizophyllum commune using NMR spectroscopy. Our data reveal that SCG but not SPG induce cytokine production from bone marrow-derived dendritic cells (BMDCs) and their major structural units are a beta-(1-->3)-d-glucan backbone with single beta-(1-->6)-d-glucosyl side branching units every three residues. PMID- 17868662 TI - Allyl deprotection of galacturonic acid derivatives: mechanistic aspects of mercuric-catalyzed prop-1-enyl acetal cleavage. AB - Different deallylation methods were assayed for selective deprotection of allyl galactopyranosiduronic acid derivatives. A two-step procedure using DABCO and (Ph(3)P)(3)RhCl followed by mercuric-assisted cleavage gave quantitative yields. Reaction in the presence of [(18)O]water allowed us to obtain evidence about the mechanism of prop-1-enyl cleavage. PMID- 17868663 TI - Structure of a galactomannan isolated from the cell wall of the fungus Lineolata rhizophorae. AB - The structure of an alkali-extracted water-soluble polysaccharide isolated from the cell wall of the marine fungus Lineolata rhizophorae has been elucidated by chemical and spectroscopic means. The idealized repeating unit of this novel structure is [carbohydrate structure: see text] being m approximately 41, n approximately 2, and p approximately 5. PMID- 17868664 TI - The influence of headgroup structure and fatty acyl chain saturation of phospholipids on monolayer behavior: a comparative rheological study. AB - This paper compares six phospholipidic monolayers at the water/chloroform interface by performing dilational rheological measurements with a drop tensiometer apparatus. The chosen lipids differ both in their headgroup structure and fatty acyl chain saturation or symmetry. The study concentrated on monolayers formed with DPPC, DPPE, DOPC, DOPE, POPC and POPE. Using a generalized Maxwell rheological model, transposed at the interface, the intimate intermolecular interactions between amphiphilic molecules are studied on and off the monolayer plane. The equilibrium and nonequilibrium phenomena are analyzed and, respectively, correlated with monolayer cohesion and with monolayer/sub-surface interactions. The purpose of this work is to gain further insights into the influences (as slight as they are) of the weak changes in phospholipid structure and on the behavior of the monolayers. The results, widely described, provide further details on nuances existing between very similar molecules, and likewise, on the synergies created between the different effects. PMID- 17868665 TI - The C-allele of tissue inhibitor of metalloproteinases 2 is associated with increased magnitude of QT dispersion prolongation in elderly Chinese - 4-year follow-up study. AB - BACKGROUND: Matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases (TIMP) trigger the signal cascade instigating cardiac remodeling and fibrosis, which lead to changes of repolarization variables. We investigate the influence of MMP9-1562 C/T and TIMP2-418 G/C gene polymorphisms on repolarization parameters including QT dispersion (QTd) and the peak and the end of the T wave interval (Tpe) in a prospective cohort. METHODS: Of 1500 people screened, 106 elderly Chinese without organic heart disease were recruited and received electrocardiography at the baseline, second and 4th year follow-ups. The QTc (corrected QT), QTd, QTc dispersion (QTcd) and Tpe were manually calculated. RESULTS: Age was 72.7+/-4.1 y (range 62-81 y). QTd, QTcd and Tpe were significantly prolonged (all p <0.001 at the 2nd and 4th year). At the 4th year the magnitude of QTd prolongation but not Tpe was significantly higher in subjects carrying the TIMP2 C-allele than non C-allele carriers (p=0.033) as well as QTcd (p=0.010). This association was still significant in multivariate analyses (p=0.012 and p=0.003 for QTd and QTcd, respectively) but not in MMP9 genotype. CONCLUSIONS: The elderly Chinese with TIMP2 C-allele have higher magnitude of QTd and QTcd prolongation. PMID- 17868666 TI - Beyond Simulation-Theory and Theory-Theory: why social cognitive neuroscience should use its own concepts to study "theory of mind". AB - The debate between Simulation-Theory (ST) and Theory-Theory (TT) provides the dominant theoretical framework for research on "theory of mind" (ToM). Behavioural research has failed to provide clear methods for discriminating between these theories, but a number of recent studies have claimed that neuroimaging methods do allow key predictions of ST and TT to be tested. In the current paper it is argued that neuroimaging studies have not in fact provided any data that discriminates between ST and TT accounts of propositional attitude ascription, and moreover that it is uncertain that they will in the future. However, it is also argued that the fault lies with the ST/TT debate, not with the methods and concepts of neuroimaging research. Neuroimaging can certainly contribute to our understanding of ToM, and should contribute to the project of developing theoretical models more firmly grounded in specific cognitive and neural processes than ST or TT. PMID- 17868667 TI - Computer simulation of damage on distal femoral articular cartilage after meniscectomies. AB - It is commonly accepted that total or partial meniscectomies cause wear of articular cartilages that leads to severe damage in a period of few years. This also produces alteration of the biomechanical environment and increases articular instability, with a progressive and degenerative arthrosic pathology. Due to these negative consequences, total meniscectomy technique has been avoided, with a clear preference for partial meniscectomies. Despite the better results obtained with this latter technique, it has been demonstrated that the knee still suffers progressive long-term wear, which alters the properties of the surface of articular cartilage. In this paper, a phenomenological isotropic damage model of articular cartilage is presented and implemented in a finite element code. We hypothesized that there is a relation between the increase of shear stress and cartilage degeneration. To confirm the hypothesis, the obtained results were compared to experimental ones. It is used to investigate the effect of meniscectomies on articular damage in the human knee joint. Two different situations were compared for the tibio-femoral joint: healthy and after meniscectomy. The distribution of damaged regions and the damage level distribution resulted qualitatively similar to experimental results, showing, for instance that, after meniscectomy, significant degeneration occurs in the lateral compartment. A noteworthy result was that patterns of damage in a total meniscectomy model give better agreement to clinical results when using relative increases in shear stress, rather than an absolute shear stress criterion. The predictions for partial meniscectomies indicated the relative severity of the procedures. PMID- 17868668 TI - Sex-specific expression of a HOX gene associated with rapid morphological evolution. AB - Animal diversity is shaped by the origin and diversification of new morphological structures. Many examples of evolutionary innovations are provided by male specific traits involved in mating and sexual selection. The origin of new sex specific characters requires the evolution of new regulatory interactions between sex-determining genes and genes that control spatial patterning and cell differentiation. Here, we show that sex-specific regulation of the HOX gene Sex combs reduced (Scr) is associated with the origin and evolution of the Drosophila sex comb - a novel and rapidly diversifying male-specific organ. In species that primitively lack sex combs, Scr expression shows little spatial modulation, whereas in species that have sex combs, Scr is upregulated in the presumptive sex comb region and is frequently sexually dimorphic. Phylogenetic analysis shows that sex-specific regulation of Scr has been gained and lost multiple times in Drosophila evolution and correlates with convergent origin of similar sex comb morphologies in several independent lineages. Some of these transitions occurred on microevolutionary timescales, indicating that HOX gene expression can evolve with surprising ease. This is the first example of a sex-specific regulation of a HOX gene contributing to the development and evolution of a secondary sexual trait. PMID- 17868669 TI - Actomyosin contractility and microtubules drive apical constriction in Xenopus bottle cells. AB - Cell shape changes are critical for morphogenetic events such as gastrulation, neurulation, and organogenesis. However, the cell biology driving cell shape changes is poorly understood, especially in vertebrates. The beginning of Xenopus laevis gastrulation is marked by the apical constriction of bottle cells in the dorsal marginal zone, which bends the tissue and creates a crevice at the blastopore lip. We found that bottle cells contribute significantly to gastrulation, as their shape change can generate the force required for initial blastopore formation. As actin and myosin are often implicated in contraction, we examined their localization and function in bottle cells. F-actin and activated myosin accumulate apically in bottle cells, and actin and myosin inhibitors either prevent or severely perturb bottle cell formation, showing that actomyosin contractility is required for apical constriction. Microtubules were localized in apicobasally directed arrays in bottle cells, emanating from the apical surface. Surprisingly, apical constriction was inhibited in the presence of nocodazole but not taxol, suggesting that intact, but not dynamic, microtubules are required for apical constriction. Our results indicate that actomyosin contractility is required for bottle cell morphogenesis and further suggest a novel and unpredicted role for microtubules during apical constriction. PMID- 17868670 TI - Pharmacological evidence for the involvement of the opioid system in the antidepressant-like effect of adenosine in the mouse forced swimming test. AB - This study investigated the involvement of the opioid system in the antidepressant-like effect of adenosine in the forced swimming test. The effect of adenosine (10 mg/kg, i.p.) was prevented by the pretreatment of mice with naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist), naltrindole (3 mg/kg, i.p., a selective delta-opioid receptor antagonist), clocinnamox (1 mg/kg, i.p., an irreversible mu-opioid receptor antagonist), and 2-(3,4 dichlorophenyl)-Nmethyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1 pyrrolidinyl)ethyl]acetamide (DIPPA; 1 mg/kg, i.p., a selective kappa-opioid receptor antagonist), but not with naloxone methiodide (1 mg/kg, s.c., a nonselective opioid receptor antagonist that does not cross the blood-brain barrier). Naloxone also prevented the anti-immobility effect of cyclohexyladenosine (CHA, 0.1 mg/kg, i.p., a selective adenosine A(1) receptor agonist) and N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA, 1 mg/kg, i.p., a selective adenosine A(2A) receptor agonist). The administration of DIPPA (0.1 mg/kg, i.p.) or morphine (1 mg/kg, s.c., a nonselective opioid receptor agonist), but not naltrindole (0.3 mg/kg, i.p.) and clocinnamox (0.1 mg/kg, i.p.) potentiated the effect of a subeffective dose of adenosine (1 mg/kg, i.p.) in the forced swimming test, without affecting the locomotor activity. No additive effect in the immobility time was observed when mice were treated with morphine (5 mg/kg, s.c.) plus adenosine (10 mg/kg, i.p.). These results indicate that the anti-immobility effect of adenosine in the forced swimming test, via adenosine A(1) and A(2A) receptors, is mediated by an interaction with the opioid system, likely dependent on an activation of mu- and delta-opioid receptors and an inhibition of kappa-opioid receptors. PMID- 17868671 TI - Mouse Prickle1 and Prickle2 are expressed in postmitotic neurons and promote neurite outgrowth. AB - The Drosophila planar cell polarity (PCP) gene prickle has been previously indicated as one of the regulators of gastrulation in the early embryonic stage. However, the functional role of prickle in the brain in particular is not known. We first indicated that mouse Prickle1 and Prickle2 are continually expressed in the brain throughout the embryonic stages and are observed to be specifically expressed in the postmitotic neurons. Furthermore, Prickle1 or Prickle2 depletion effectively decreases the neurite outgrowth levels of mouse neuroblastoma Neuro2a cells. These results indicate that mouse Prickle1 and Prickle2 possibly regulate positive neurite formation during brain development. PMID- 17868672 TI - Casein kinase 2 is the major enzyme in brain that phosphorylates Ser129 of human alpha-synuclein: Implication for alpha-synucleinopathies. AB - In Lewy body diseases and multiple system atrophy, alpha-synuclein is hyperphosphorylated at Ser129, suggesting a role in pathogenesis. Here, we report purification of the protein kinase in rat brain that phosphorylates Ser129 and its identification as casein kinase-2 (CK2). We show that most of the activity can be inhibited by heparin, an inhibitor of CK2. Phosphorylated Ser129 was detected in primary cultured neurons and inhibited by CK2 inhibitors. In some cases of Lewy body disease, CK2-like immunoreactivity was recovered in the sarkosyl-insoluble fraction, which was enriched in phosphorylated alpha synuclein. Taken together, these findings suggest that CK2 may be involved in the hyperphosphorylation of alpha-synuclein in alpha-synucleinopathies. PMID- 17868673 TI - Immunocytochemical detection of leptin-like immunoreactivity in the chicken gastroenteric tract. AB - Leptin is a hormone produced and secreted mainly by adipocytes, but also by other tissues such as placenta, brain, mammary, and pituitary glands. The gastric epithelium has also been reported as a source of leptin in mammals. In this study we examined the presence of leptin in the chicken gastroenteric tract by immunohistochemistry and Western blotting. Strong and widespread leptin-like immunoreactivity was observed in the mucosal epithelium of proventriculus plicae and in the epithelium of the complex compound glands. Numerous leptin immunoreactive cells were found along lining epithelium of duodenum villi, while few leptin-immunoreactive cells were observed in the basal zone of duodenum glands. Many leptin-immunoreactive cells were found in the caeca at the basal zone of glands, while very few leptin-immunoreactive cells were found in the deep glandular structures of the large intestine. In the homogenates of chicken gastroenteric tract the protein detected using a human leptin-specific antibody had estimated molecular weight of approximately 15-16 kDa. To our knowledge, this is the first report demonstrating leptin-like protein distribution in the whole gastroenteric tract of bird. This finding constitute important data for the further understanding of the mechanism that regulate feeding behaviour in birds, farm animal for which the control of food intake and fatness are a high economic interest. PMID- 17868674 TI - Interactions between estrogen effects and hunger effects in ovariectomized female mice. I. Measures of arousal. AB - Measures of arousal were used to study effects of estradiol and food restriction, and their potential interactions, in ovariectomized female C57Bl/6 mice. It was hypothesized based on a proposed theoretical equation [Pfaff, D.W., 2006a. Brain Arousal and Information Theory. Harvard University Press, Cambridge, Pfaff, D.W., (Ed.), 2006b. Knobil and Neill's The Physiology of Reproduction, 3rd edition. Elsevier/Academic Press, San Diego] that each treatment would increase arousal related behaviors and that their combination would further increase arousal behavior. Following baseline testing, animals (n=28) were divided into 3 groups that, in different experimental phases, received either estradiol (in subcutaneous capsules), restricted diet (a liquid diet providing 60% of daily caloric requirements) or a combination of those two. An automated arousal behavior monitoring system was used to measure home cage voluntary motor activity and sensory responsiveness, these being components of a new operational definition of 'generalized arousal'. KEY FINDINGS: (1) During the light, all treatments reduced voluntary activity. (2) In the dark, estrogens increased, while estrogens in combination with restricted diet decreased, horizontal activity. (3) In the dark, restricted diet alone had little effect on voluntary activity, but reduced it when combined with estrogen treatment. (4) All treatments reduced responses to the olfactory stimulus. The dependence of results on time of day was unexpected. Further, different patterns of results for the three treatments suggest that estrogens and food restriction did not have equivalent or additive effects on arousal. While contrary to the main prediction, these findings are discussed in terms of the animals' adaptive preparations for reproduction [Schneider, J.E., 2006. Metabolic and hormonal control of the desire for food and sex: implications for obesity and eating disorders. Horm. Behav. 50, 562-571]. PMID- 17868675 TI - Obstetric fistulas: a clinical review. AB - A high proportion of genitourinary fistulas have an obstetric origin. Obstetric fistulas are caused by prolonged obstructed labor coupled with a lack of medical attention. While successful management with prolonged bladder drainage has occasionally been reported, mature fistulas require formal operative repair, and it is crucial that the first repair is done properly. The literature reports 3 approaches to fistula repair: vaginal, abdominal, and combined vaginal and abdominal. Many authors report high success rates for the surgical closure of obstetric fistulas at the time of hospital discharge, without further evaluation of the repair's effect on urinary continence or subsequent quality of life. Data on obstetric fistulas are scarce, and thus many questions regarding fistula management remain unanswered. A standardized terminology and classification, as well as a data reporting system on the surgical management of obstetric fistulas and its outcomes, are critical steps that need to be taken immediately. PMID- 17868676 TI - The role of delayed childbearing in the prevention of obstetric fistulas. AB - OBJECTIVE: To examine the role of delayed childbearing in the prevention of obstetric fistulas (OFs). METHODS: Data on 4798 deliveries in Niger (1995-1998), 3552 in Nigeria (1996-1999), and 6789 in Tanzania (1991-1996) were analyzed with logistic regression models. RESULTS: Young maternal age and primiparous status were identified as correlates of prolonged/obstructed labor. The annual incidence of OFs in Nigeria was found to be 2.11 per 1000 births, with 9817 cases developing each year, 28% in women and girls younger than 20 years. The predicted proportion of women experiencing prolonged/obstructed labor would be reduced by 11.2% in Niger, 11.4% in Nigeria, and 13.1% in Tanzania if the risks associated with young maternal age at first delivery and primiparity were eliminated. CONCLUSIONS: Community programs to educate young, newly married women about delaying childbearing until they reach physical maturity should be implemented in countries with a high incidence of OFs. PMID- 17868677 TI - Natural regulatory (CD4+CD25+FOXP+) T cells control the production of pro inflammatory cytokines during Plasmodium chabaudi adami infection and do not contribute to immune evasion. AB - Different functions have been attributed to natural regulatory CD4+CD25+FOXP+ (Treg) cells during malaria infection. Herein, we assessed the role for Treg cells during infections with lethal (DS) and non-lethal (DK) Plasmodium chabaudi adami parasites, comparing the levels of parasitemia, inflammation and anaemia. Independent of parasite virulence, the population of splenic Treg cells expanded during infection, and the absolute numbers of activated CD69+ Treg cells were higher in DS-infected mice. In vivo depletion of CD25+ T cells, which eliminated 80% of CD4+FOXP3+CD25+ T cells and 60-70% of CD4+FOXP3+ T cells, significantly decreased the number of CD69+ Treg cells in mice with lethal malaria. As a result, higher parasite burden and morbidity were measured in the latter, whereas the kinetics of infection with non-lethal parasites remained unaffected. In the absence of Treg cells, parasite-specific IFN-gamma responses by CD4+ T cells increased significantly, both in mice with lethal and non-lethal infections, whereas IL-2 production was only stimulated in mice with non-lethal malaria. Following the depletion of CD25+ T cells, the production of IL-10 by CD90(-) cells was also enhanced in infected mice. Interestingly, a potent induction of TNF-alpha and IFN-gamma production by CD4+ and CD90(-) lymphocytes was measured in DS-infected mice, which also suffered severe anaemia earlier than non-depleted infected controls. Taken together, our data suggest that the expansion and activation of natural Treg cells represent a counter-regulatory response to the overwhelming inflammation associated with lethal P.c. adami. This response to infection involves TH1 lymphocytes as well as cells from the innate immune system. PMID- 17868678 TI - Atorvastatin increases HDL cholesterol by reducing CETP expression in cholesterol fed APOE*3-Leiden.CETP mice. AB - OBJECTIVE: In addition to lowering low-density lipoprotein (LDL)-cholesterol, statins modestly increase high-density lipoprotein (HDL)-cholesterol in humans and decrease cholesteryl ester transfer protein (CETP) mass and activity. Our aim was to determine whether the increase in HDL depends on CETP expression. METHODS AND RESULTS: APOE*3-Leiden (E3L) mice, with a human-like lipoprotein profile and a human-like responsiveness to statin treatment, were crossbred with mice expressing human CETP under control of its natural flanking regions resulting in E3L.CETP mice. E3L and E3L.CETP mice were fed a Western-type diet with or without atorvastatin. Atorvastatin (0.01% in the diet) reduced plasma cholesterol in both E3L and E3L.CETP mice (-26 and -33%, P<0.05), mainly in VLDL, but increased HDL cholesterol only in E3L.CETP mice (+52%). Hepatic mRNA expression levels of genes involved in HDL metabolism, such as phospholipid transfer protein (Pltp), ATP binding cassette transporter A1 (Abca1), scavenger receptor class B type I (Sr b1), and apolipoprotein AI (Apoa1), were not differently affected by atorvastatin in E3L.CETP mice as compared to E3L mice. However, in E3L.CETP mice, atorvastatin down-regulated the hepatic CETP mRNA expression (-57%; P<0.01) as well as the total CETP level (-29%) and cholesteryl esters (CE) transfer activity (-36%; P<0.05) in plasma. CONCLUSIONS: Atorvastatin increases HDL-cholesterol in E3L.CETP mice by reducing the CETP-dependent transfer of cholesterol from HDL to (V)LDL, as related to lower hepatic CETP expression and a reduced plasma (V)LDL pool. PMID- 17868679 TI - Metabolic syndrome features small, apolipoprotein A-I-poor, triglyceride-rich HDL3 particles with defective anti-apoptotic activity. AB - The metabolic syndrome (MetS) phenotype is typically characterized by visceral obesity, insulin resistance, atherogenic dyslipidemia involving hypertriglyceridemia and subnormal levels of high density lipoprotein-cholesterol (HDL-C), oxidative stress and elevated cardiovascular risk. The potent antioxidative activity of small HDL3 is defective in MetS [Hansel B, et al. J Clin Endocrinol Metab 2004;89:4963-71]. We evaluated the functional capacity of small HDL3 particles from MetS subjects to protect endothelial cells from apoptosis induced by mildly oxidized low-density lipoprotein (oxLDL). MetS subjects presented an insulin-resistant obese phenotype, with hypertriglyceridemia, elevated apolipoprotein B and insulin levels, but subnormal HDL-C concentrations and chronic low grade inflammation (threefold elevation of C reactive protein). When human microvascular endothelial cells (HMEC-1) were incubated with oxLDL (200 microg apolipoprotein B/ml) in the presence or absence of control HDL subfractions (25 microg protein/ml), small, dense HDL3b and 3c significantly inhibited cellular annexin V binding and intracellular generation of reactive oxygen species. The potent anti-apoptotic activity of small HDL3c particles was reduced (-35%; p<0.05) in MetS subjects (n=16) relative to normolipidemic controls (n=7). The attenuated anti-apoptotic activity of HDL3c correlated with abdominal obesity, atherogenic dyslipidemia and systemic oxidative stress (p<0.05), and was intimately associated with altered physicochemical properties of apolipoprotein A-I (apoA-I)-poor HDL3c, involving core cholesteryl ester depletion and triglyceride enrichment. We conclude that in MetS, apoA-I-poor, small, dense HDL3c exert defective protection of endothelial cells from oxLDL-induced apoptosis, potentially reflecting functional anomalies intimately associated with abnormal neutral lipid core content. PMID- 17868680 TI - Effect of a 4-year workplace-based physical activity intervention program on the blood lipid profiles of participating employees: the high-risk and population strategy for occupational health promotion (HIPOP-OHP) study. AB - Individuals who are physically fit or engage in regular physical activity have a lower incidence of cardiovascular disease and risk of mortality. We conducted a large-scale controlled trial of interventions to decrease cardiovascular risk factors, during which we assessed the effect of a workplace-based intervention program, which was part of a population strategy for promoting long-term increases in physical activity, on the blood lipid profiles of participating employees. Data were collected from 2929 participants and this report presents the results of a survey conducted in five factories for the intervention group and five factories for the control group at baseline and year 5. The absolute/proportional changes in HDL-cholesterol were 2.7 mg/dL (4.8%) in the intervention group and -0.6 mg/dL (-1.0%) in the control group. The differences between the two groups in the change in serum levels of HDL-cholesterol were highly significant (p<0.001) in each analysis of covariance, in which the number of cigarettes smoked was included or excluded. In the intervention group, the daily walking time increased significantly (p<0.001) when compared between baseline and year 5, whereas no significant difference was observed in daily walking time in the control group over the identical period. Our results show that an intervention program promoting physical activity raises serum HDL cholesterol levels of middle-aged employees. Increased awareness of the benefits of physical activity, using environmental rearrangement and health promotion campaigns, which especially target walking, may have contributed to a beneficial change in serum HDL-cholesterol levels in the participants. PMID- 17868681 TI - Determination of nitrate esters in water samples Comparison of efficiency of solid-phase extraction and solid-phase microextraction. AB - This paper deals with comparison of efficiency of extraction techniques (solid phase extraction, SPE and solid-phase microextraction, SPME) used for extraction of nitrate esters (ethyleneglycoldinitrate, EGDN and nitroglycerin, NG), representing the first step of the method of quantitative determination of trace concentrations of nitrate esters in water samples. EGDN and NG are subsequently determined by means of high-performance liquid chromatography with ultraviolet detection (HPLC-UV). Optimization of SPE and SPME conditions was carried out using model water samples. Seven SPE cartridges were tested and the conditions were optimized (type of sorbent, type and volume of solvent to be used as eluent). For both nitrate esters the limit of detection (LOD) and the limit of quantification (LOQ) obtained using SPE/HPLC-UV were 0.23 microg mL(-1) and 0.70 microg mL(-1), respectively. Optimization of SPME conditions: type of SPME fibre (four fibres were tested), type and time of sorption/desorption, temperature of sorption. PDMS/DVB (polydimethylsiloxane/divinylbenzene) fibre coating proved to be suitable for extraction of EGDN and NG. For this fibre the LOD and the LOQ for both nitrate esters were 0.16 microg mL(-1) and 0.50 microg mL(-1), respectively. Optimized methods SPE/HPLC-UV and SPME/HPLC-UV were then used for quantitative determination of nitrate esters content in real water samples from the production of EGDN and NG. PMID- 17868682 TI - Introducing interacting diffuse layers in TLM calculations: a reappraisal of the influence of the pore size on the swelling pressure and the osmotic efficiency of compacted bentonites. AB - The truncation of the Gouy-Chapman diffuse part in compacted clay-rocks and bentonite is introduced into the electrical triple-layer model (TLM) recently developed by P. Leroy and A. Revil [J. Colloid Interface Sci. 270 (2004) 371]. The new model is used to explain the dependence of the osmotic efficiency and the swelling pressure as functions of the mean pore size of the medium, determined from the porosity and the specific surface. The truncation of the diffuse layer introduces a new variable in the system of equations to be solved, the electrical potential at the midplane between adjacent charged surfaces. This new variable is evaluated through a Taylor expansion of the electrical potential. The present model is able to capture the variation of the osmotic efficiency and the swelling pressure with the mean pore size. The partition of counterions between the Stern layer and the diffuse layer as a function of the pore size calculated by the TLM also shows a good consistency with the model. This implies that more than 90% of the counterions are located in the Stern layer. PMID- 17868683 TI - Mechanism study on adsorption of acidified multiwalled carbon nanotubes to Pb(II). AB - Adsorption of acidified multiwalled carbon nanotubes (MWCNTs) to heavy metal using Pb(II) as a model was investigated and characterized by many techniques. The main adsorption mechanism of acidified MWCNTs to Pb(II) is proposed on the basis of adequate analysis. The results show that the oxygenous functional groups can be formed on MWCNTs after MWCNTs were treated by concentrated nitric acid. The oxygenous functional groups play an important role in Pb(II) adsorption to form chemical complex adsorption, which accounts for 75.3% of all the Pb(II) adsorption capacity. The Pb(II) in the form of PbO, Pb(OH)(2), and PbCO(3) adsorbed on the surface of the acidified MWCNTs is only 3.4% of the total Pb(II) adsorption capacity. The Pb(II) species adsorbed on acidified MWCNTs mainly aggregate on the ends and at the defects sites on the acidified MWCNTs. PMID- 17868684 TI - False positive reactivity of recombinant, diagnostic, glycoproteins produced in High Five insect cells: effect of glycosylation. AB - Baculovirus-mediated expression of recombinant proteins for use in diagnostic assays is commonplace. We expressed a diagnostic antigen for cysticercosis, GP50, caused by the larval stage of Taenia solium, in both High Five and Sf9 insect cells. Upon evaluation of the specificity of recombinant GP50 (rGP50) in a western blot assay, we observed that 12.5% (21/168) of the serum samples from persons with a variety of parasitic infections other than cysticercosis reacted positive when rGP50 was produced in High Five cells. The same samples reacted negative when rGP50 was produced in Sf9 cells. The false positive reactivities of these other parasitic infection sera were abolished when rGP50, expressed in High Five cells, was deglycosylated. In addition, the same sera that reacted with rGP50 from High Five cells also reacted with recombinant human transferrin (rhTf) when expressed in High Five cells, but not Sf9 cells. High Five cells, but not Sf9 cells, modify many glycoproteins with a core alpha(1,3)-fucose. This same modification is found in the glycoproteins of several parasitic worms and is known to be immunogenic. Since the distribution of these worms is widespread and millions of people are infected, the use of recombinant proteins with N-linked glycosylation produced in High Five cells for diagnostic antigens is likely to result in a number of false positive reactions and a decrease in assay specificity. PMID- 17868685 TI - Mechanical unbinding of abeta peptides from amyloid fibrils. AB - Using the experimental structures of Abeta amyloid fibrils and all-atom molecular dynamics, we study the force-induced unbinding of Abeta peptides from the fibril. We show that the mechanical dissociation of Abeta peptides is highly anisotropic and proceeds via different pathways when force is applied in parallel or perpendicular direction with respect to the fibril axis. The threshold forces associated with lateral unbinding of Abeta peptides exceed those observed during the mechanical dissociation along the fibril axis. In addition, Abeta fibrils are found to be brittle in the lateral direction of unbinding and soft along the fibril axis. Lateral mechanical unbinding and the unbinding along the fibril axis load different types of fibril interactions. Lateral unbinding is primarily determined by the cooperative rupture of fibril backbone hydrogen bonds. The unbinding along the fibril axis largely depends on the interpeptide Lys-Asp electrostatic contacts and the hydrophobic interactions formed by the Abeta C terminal. Due to universality of the amyloid beta structure, the anisotropic mechanical dissociation observed for Abeta fibrils is likely to be applicable to other amyloid assemblies. The estimates of equilibrium forces required to dissociate Abeta peptide from the amyloid fibril suggest that these supramolecular structures are mechanically stronger than most protein domains. PMID- 17868686 TI - Filling a hole in cytochrome P450 BM3 improves substrate binding and catalytic efficiency. AB - Cytochrome P450BM3 (CYP102A1) from Bacillus megaterium, a fatty acid hydroxylase, is a member of a very large superfamily of monooxygenase enzymes. The available crystal structures of the enzyme show non-productive binding of substrates with their omega-end distant from the iron in a hydrophobic pocket at one side of the active site. We have constructed and characterised mutants in which this pocket is filled by large hydrophobic side-chains replacing alanine at position 82. The mutants having phenylalanine or tryptophan at this position have very much (approximately 800-fold) greater affinity for substrate, with a greater conversion of the haem iron to the high-spin state, and similarly increased catalytic efficiency. The enzyme as isolated contains bound palmitate, reflecting this much higher affinity. We have determined the crystal structure of the haem domain of the Ala82Phe mutant with bound palmitate; this shows that the substrate is binding differently from the wild-type enzyme but still distant from the haem iron. Detailed analysis of the structure indicates that the tighter binding in the mutant reflects a shift in the conformational equilibrium of the substrate free enzyme towards the conformation seen in the substrate complex rather than differences in the enzyme-substrate interactions. On this basis, we outline a sequence of events for the initial stages of the catalytic cycle. The Ala82Phe and Ala82Trp mutants are also very much more effective catalysts of indole hydroxylation than the wild-type enzyme, suggesting that they will be valuable starting points for the design of mutants to catalyse synthetically useful hydroxylation reactions. PMID- 17868687 TI - Functional specificity lies within the properties and evolutionary changes of amino acids. AB - The rapid increase in the amount of protein sequence data has created a need for automated identification of sites that determine functional specificity among related subfamilies of proteins. A significant fraction of subfamily specific sites are only marginally conserved, which makes it extremely challenging to detect those amino acid changes that lead to functional diversification. To address this critical problem we developed a method named SPEER (specificity prediction using amino acids' properties, entropy and evolution rate) to distinguish specificity determining sites from others. SPEER encodes the conservation patterns of amino acid types using their physico-chemical properties and the heterogeneity of evolutionary changes between and within the subfamilies. To test the method, we compiled a test set containing 13 protein families with known specificity determining sites. Extensive benchmarking by comparing the performance of SPEER with other specificity site prediction algorithms has shown that it performs better in predicting several categories of subfamily specific sites. PMID- 17868688 TI - Structural and biochemical basis for polyamine binding to the Tp0655 lipoprotein of Treponema pallidum: putative role for Tp0655 (TpPotD) as a polyamine receptor. AB - Tp0655 of Treponema pallidum, the causative agent of syphilis, is predicted to be a 40 kDa membrane lipoprotein. Previous sequence analysis of Tp0655 noted its homology to polyamine-binding proteins of the bacterial PotD family, which serve as periplasmic ligand-binding proteins of ATP-binding-cassette (ABC) transport systems. Here, the 1.8 A crystal structure of Tp0655 demonstrated structural homology to Escherichia coli PotD and PotF. The latter two proteins preferentially bind spermidine and putrescine, respectively. All of these proteins contain two domains that sandwich the ligand between them. The ligand binding site of Tp0655 can be occupied by 2-(N-morpholino)ethanesulfanoic acid, a component of the crystallization medium. To discern the polyamine binding preferences of Tp0655, the protein was subjected to isothermal titration calorimetric experiments. The titrations established that Tp0655 binds polyamines avidly, with a marked preference for putrescine (Kd=10 nM) over spermidine (Kd=430 nM), but the related compounds cadaverine and spermine did not bind. Structural comparisons and structure-based sequence analyses provide insights into how polyamine-binding proteins recognize their ligands. In particular, these comparisons allow the derivation of rules that may be used to predict the function of other members of the PotD family. The sequential, structural, and functional homology of Tp0655 to PotD and PotF prompt the conclusion that the former likely is the polyamine-binding component of an ABC-type polyamine transport system in T. pallidum. We thus rename Tp0655 as TpPotD. The ramifications of TpPotD as a polyamine-binding protein to the parasitic strategy of T. pallidum are discussed. PMID- 17868689 TI - Increasing methotrexate resistance by combination of active-site mutations in human dihydrofolate reductase. AB - Methotrexate-resistant forms of human dihydrofolate reductase have the potential to protect healthy cells from the toxicity of methotrexate (MTX), to improve prognosis during cancer therapy. It has been shown that synergistic MTX resistance can be obtained by combining two active-site mutations that independently confer weak MTX-resistance. In order to obtain more highly MTX resistant human dihydrofolate reductase (hDHFR) variants for this application, we used a semi-rational approach to obtain combinatorial active-site mutants of hDHFR that are highly resistant towards MTX. We created a combinatorial mutant library encoding various amino acids at residues Phe31, Phe34 and Gln35. In vivo library selection was achieved in a bacterial system on medium containing high concentrations of MTX. We characterized ten novel MTX-resistant mutants with different amino acid combinations at residues 31, 34 and 35. Kinetic and inhibition parameters of the purified mutants revealed that higher MTX-resistance roughly correlated with a greater number of mutations, the most highly-resistant mutants containing three active site mutations (Ki(MTX)=59-180 nM; wild-type Ki(MTX)<0.03 nM). An inverse correlation was observed between resistance and catalytic efficiency, which decreased mostly as a result of increased KM toward the substrate dihydrofolate. We verified that the MTX-resistant hDHFRs can protect eukaryotic cells from MTX toxicity by transfecting the most resistant mutants into DHFR-knock-out CHO cells. The transfected variants conferred survival at concentrations of MTX between 100-fold and >4000-fold higher than the wild-type enzyme, the most resistant triple mutant offering protection beyond the maximal concentration of MTX that could be included in the medium. These highly resistant variants of hDHFR offer potential for myeloprotection during administration of MTX in cancer treatment. PMID- 17868690 TI - Distinct determinants of tRNA recognition by the TrmD and Trm5 methyl transferases. AB - TrmD and Trm5 are, respectively, the bacterial and eukarya/archaea methyl transferases that catalyze transfer of the methyl group from S-adenosyl methionine (AdoMet) to the N1 position of G37 in tRNA to synthesize m1G37-tRNA. The m1G37 modification prevents tRNA frameshifts on the ribosome by assuring correct codon-anticodon pairings, and thus is essential for the fidelity of protein synthesis. Although TrmD and Trm5 are derived from unrelated AdoMet families and recognize the cofactor using distinct motifs, the question of whether they select G37 on tRNA by the same, or different, mechanism has not been answered. Here we address this question by kinetic analysis of tRNA truncation mutants that lack domains typically present in the canonical L shaped structure, and by evaluation of the site of modification on tRNA variants with an expanded or contracted anticodon loop. With both experimental approaches, we show that TrmD and Trm5 exhibit separate and distinct mode of tRNA recognition, suggesting that they evolved by independent and non-overlapping pathways from their unrelated AdoMet families. Our results also shed new light onto the significance of the m1G37 modification in the controversial quadruplet-pairing model of tRNA frameshift suppressors. PMID- 17868692 TI - A quantitative kinetic scheme for 70 S translation initiation complex formation. AB - Association of the 30 S initiation complex (30SIC) and the 50 S ribosomal subunit, leading to formation of the 70 S initiation complex (70SIC), is a critical step of the translation initiation pathway. The 70SIC contains initiator tRNA, fMet-tRNA(fMet), bound in the P (peptidyl)-site in response to the AUG start codon. We have formulated a quantitative kinetic scheme for the formation of an active 70SIC from 30SIC and 50 S subunits on the basis of parallel rapid kinetics measurements of GTP hydrolysis, Pi release, light-scattering, and changes in fluorescence intensities of fluorophore-labeled IF2 and fMet tRNA(f)(Met). According to this scheme, an initially formed labile 70 S complex, which promotes rapid IF2-dependent GTP hydrolysis, either dissociates reversibly into 30 S and 50 S subunits or is converted to a more stable form, leading to 70SIC formation. The latter process takes place with intervening conformational changes of ribosome-bound IF2 and fMet-tRNA(fMet), which are monitored by spectral changes of fluorescent derivatives of IF2 and fMet-tRNA(fMet). The availability of such a scheme provides a useful framework for precisely elucidating the mechanisms by which substituting the non-hydrolyzable analog GDPCP for GTP or adding thiostrepton inhibit formation of a productive 70SIC. GDPCP does not affect stable 70 S formation, but perturbs fMet-tRNA(fMet) positioning in the P-site. In contrast, thiostrepton severely retards stable 70 S formation, but allows normal binding of fMet-tRNA(fMet)(prf20) to the P-site. PMID- 17868691 TI - Programmed ribosomal frameshifting in SIV is induced by a highly structured RNA stem-loop. AB - Simian immunodeficiency virus (SIV), like its human homologues (HIV-1, HIV-2), requires a -1 translational frameshift event to properly synthesize all of the proteins required for viral replication. The frameshift mechanism is dependent upon a seven-nucleotide slippery sequence and a downstream RNA structure. In SIV, the downstream RNA structure has been proposed to be either a stem-loop or a pseudoknot. Here, we report the functional, structural and thermodynamic characterization of the SIV frameshift site RNA. Translational frameshift assays indicate that a stem-loop structure is sufficient to promote efficient frameshifting in vitro. NMR and thermodynamic studies of SIV RNA constructs of varying length further support the absence of any pseudoknot interaction and indicate the presence of a stable stem-loop structure. We determined the structure of the SIV frameshift-inducing RNA by NMR. The structure reveals a highly ordered 12 nucleotide loop containing a sheared G-A pair, cross-strand adenine stacking, two G-C base-pairs, and a novel CCC triloop turn. The loop structure and its high thermostability preclude pseudoknot formation. Sequence conservation and modeling studies suggest that HIV-2 RNA forms the same structure. We conclude that, like the main sub-groups of HIV-1, SIV and HIV-2 utilize stable stem-loop structures to function as a thermodynamic barrier to translation, thereby inducing ribosomal pausing and frameshifting. PMID- 17868693 TI - The regulation of myosin binding to actin filaments by Lethocerus troponin. AB - Lethocerus indirect flight muscle has two isoforms of troponin C, TnC-F1 and F2, which are unusual in having only a single C-terminal calcium binding site (site IV, isoform F1) or one C-terminal and one N-terminal site (sites IV and II, isoform F2). We show here that thin filaments assembled from rabbit actin and Lethocerus tropomyosin (Tm) and troponin (Tn) regulate the binding of rabbit myosin to rabbit actin in much the same way as the mammalian regulatory proteins. The removal of calcium reduces the rate constant for S1 binding to regulated actin about threefold, independent of which TmTn is used. This is consistent with calcium removal causing the TmTn to occupy the B or blocked state to about 70% of the total. The mid point pCa for the switch differed for TnC-F1 and F2 (pCa 6.9 and 6.0, respectively) consistent with the reported calcium affinities for the two TnCs. Equilibrium titration of S1 binding to regulated actin filaments confirms calcium regulated binding of S1 to actin and shows that in the absence of calcium the three actin filaments (TnC-F1, TnC-F2 and mammalian control) are almost indistinguishable in terms of occupancy of the B and C states of the filament. In the presence of calcium TnC-F2 is very similar to the control with approximately 80% of the filament in the C-state and 10-15% in the fully on M State while TnC-F1 has almost 50% in each of the C and M states. This higher occupancy of the M-state for TnC-F1, which occurs above pCa 6.9, is consistent with this isoform being involved in the calcium activation of stretch activation. However, it leaves unanswered how a C-terminal calcium binding site of TnC can activate the thin filament. PMID- 17868694 TI - Structural and kinetic characterization of quinolinate phosphoribosyltransferase (hQPRTase) from homo sapiens. AB - Human quinolinate phosphoribosyltransferase (EC 2.4.2.19) (hQPRTase) is a member of the type II phosphoribosyltransferase family involved in the catabolism of quinolinic acid (QA). It catalyses the formation of nicotinic acid mononucleotide from quinolinic acid, which involves a phosphoribosyl transfer reaction followed by decarboxylation. hQPRTase has been implicated in a number of neurological conditions and in order to study it further, we have carried out structural and kinetic studies on recombinant hQPRTase. The structure of the fully active enzyme overexpressed in Escherichia coli was solved using multiwavelength methods to a resolution of 2.0 A. hQPRTase has a alpha/beta barrel fold sharing a similar overall structure with the bacterial QPRTases. The active site of hQPRTase is located at an alpha/beta open sandwich structure that serves as a cup for the alpha/beta barrel of the adjacent subunit with a QA binding site consisting of three arginine residues (R102, R138 and R161) and two lysine residues (K139 and K171). Mutation of these residues affected substrate binding or abolished the enzymatic activity. The kinetics of the human enzyme are different to the bacterial enzymes studied, hQPRTase is inhibited competitively and non competitively by one of its substrates, 5-phosphoribosylpyrophosphate (PRPP). The human enzyme adopts a hexameric arrangement, which places the active sites in close proximity to each other. PMID- 17868695 TI - The translational fidelity function of IF3 during transition from the 30 S initiation complex to the 70 S initiation complex. AB - IF3 has a fidelity function in the initiation of translation, inducing the dissociation of fMet-tRNA(fMet) from the 30 S initiation complexes (30SIC) containing a non-canonical initiation triplet (e.g. AUU) in place of a canonical initiation triplet (e.g., AUG). IF2 has a complementary role, selectively promoting initiator tRNA binding to the ribosome. Here, we used parallel rapid kinetics measurements of GTP hydrolysis, Pi release, light-scattering, and changes in intensities of fluorophore-labeled IF2 and fMet-tRNA(fMet) to determine the effects on both 30SIC formation and 30SIC conversion to 70 S initiation complexes (70SIC) of (a) substituting AUG with AUU, and/or (b) omitting IF3, and/or (c) replacing GTP with the non-hydrolyzable analog GDPCP. We demonstrate that the presence or absence of IF3 has, at most, minor effects on the rate of 30SIC formation using either AUG or AUU as the initiation codon, and conclude that the high affinity of IF2 for both 30 S subunit and initiator tRNA overrides any perturbation of the codon-anticodon interaction resulting from AUU for AUG substitution. In contrast, replacement of AUG by AUU leads to a dramatic reduction in the rate of 70SIC formation from 30SIC upon addition of 50 S subunits. Interpreting our results in the framework of a quantitative kinetic scheme leads to the conclusion that, within the overall process of 70SIC formation, the step most affected by substituting AUU for AUG involves the conversion of an initially labile 70 S ribosome into a more stable complex. In the absence of IF3, the difference between AUG and AUU largely disappears, with each initiation codon affording rapid 70SIC formation, leading to the hypothesis that it is the rate of IF3 dissociation from the 70 S ribosome during IC70S formation that is critical to its fidelity function. PMID- 17868696 TI - Optimization of the gbeta1 domain by computational design and by in vitro evolution: structural and energetic basis of stabilization. AB - Computational design and in vitro evolution are major strategies for stabilizing proteins. For the four critical positions 16, 18, 25, and 29 of the B domain of the streptococcal protein G (Gbeta1), they identified the same optimal residues at positions 16 and 25, but not at 18 and 29. Here we analyzed the energetic contributions of the residues from these two approaches by single and double mutant analyses and determined crystal structures for a variant from the calculation (I16/L18/E25/K29) and from the selection (I16/I18/E25/F29). The structural analysis explains the observed differences in stabilization. Residues 16, 18, and 29 line an invagination, which results from a packing defect between the helix and the beta-sheet of Gbeta1. In all stabilized variants, residues with larger side-chains occur at these positions and packing is improved. In the selected variant, packing is better optimized than in the computed variant. Such differences in side-chain packing strongly affect stability but are difficult to evaluate by computation. PMID- 17868697 TI - The N-terminal helix is a post-assembly clamp in the bacterial outer membrane protein PagP. AB - The Escherichia coli outer membrane beta-barrel enzyme PagP and its homologues are unique in that the eight-stranded barrel is tilted by about 25 degrees with respect to the membrane normal and is preceded by a 19-residue amphipathic alpha helix. To investigate the role of this helix in the folding and stability of PagP, mutants were generated in which the helix was deleted (Delta(1-19)), or in which residues predicted to be involved in helix-barrel interactions were altered (W17A or R59L). The ability of the variants to insert into detergent micelles or liposomes was studied in vitro using circular dichroism, fluorescence, Fourier transform infrared spectroscopy, electrophoretic mobility and gain of enzyme activity. The data show that PagP, initially unfolded in 5% (w/v) perfluoro octanoic acid or 6 M guanidinium chloride, inserts spontaneously and folds quantitatively to an active conformation into detergent micelles of cyclofos-7 or into large vesicles of diC(12:0)-phosphatidylcholine (diC(12:0)PC), respectively, the latter in the presence of 7 M urea. Successful refolding of all variants into both micelles and liposomes ruled out an essential role for the helix or helix barrel interactions in folding and membrane insertion. Measurements of thermal stability indicated that the variants R59L, W17A/R59L and Delta(1-19) were destabilised substantially compared with wild-type PagP. However, in contrast to the other variants, destabilisation of the W17A variant relative to wild-type PagP was much greater in liposomes than in micelles. Analysis of the kinetics of folding and unfolding of all variants in diC(12:0)PC liposomes suggested that this destabilisation arises predominantly from an increased dissociation of the refolded variant proteins from the lipid-inserted state. The data support the view that the helix of PagP is not required for folding and assembly, but instead acts as a clamp, stabilising membrane-inserted PagP after folding and docking with the membrane are complete. PMID- 17868698 TI - A multimodal assessment of the relationship between emotion dysregulation and borderline personality disorder among inner-city substance users in residential treatment. AB - The concept of emotion dysregulation has been integrated into theory and treatment for borderline personality disorder (BPD), despite limited empirical support. Expanding upon existing research on the relationship between emotion dysregulation and BPD, the present study utilized a multimodal approach to the assessment of emotion dysregulation (including two behavioral measures of the willingness to tolerate emotional distress, and a self-report measure of emotion dysregulation broadly defined) to examine the relationship between emotion dysregulation and BPD among inner-city substance users in residential treatment (n=76, with 25 meeting criteria for BPD). Results provide laboratory-based evidence for heightened emotion dysregulation in BPD, extending extant research on BPD to underserved clinical populations. Specifically, the presence of a BPD diagnosis among a sample of inner-city inpatient substance users was associated with both higher scores on the self-report measure of emotion dysregulation and less willingness to tolerate emotional distress on the behavioral measures of emotion dysregulation. Moreover, both self-report and behavioral measures of emotion dysregulation accounted for unique variance in BPD status, suggesting the importance of utilizing comprehensive assessments of emotion dysregulation within studies of BPD. Findings suggest the need to further explore the role of emotion dysregulation in the development and maintenance of BPD among inner-city substance users in residential treatment. PMID- 17868699 TI - Mesenchymal stem cells attenuate hypoxic pulmonary vasoconstriction by a paracrine mechanism. AB - BACKGROUND: Hypoxic pulmonary vasoconstriction (HPV) may be an adaptive mechanism to correct ventilation-perfusion mismatch in the face of hypoxia. In chronic hypoxia, prolonged vasoconstriction may result in pulmonary hypertension and cor pulmonale. It has been shown that during chronic hypoxia, mesenchymal stem cells (MSCs) may contribute to pulmonary vascular remodeling, anti-inflammation, and vascular stability. Also, MSCs have been shown to release growth factors when stressed by hypoxia. We hypothesized that MSCs reduce HPV by a paracrine mechanism. To test this, MSCs were stressed by hypoxia in tissue culture and the cell-free media was then used to treat the pulmonary arteries subjected to HPV. METHODS: Adult male (250-350 g) Sprague Dawley rat pulmonary arteries (n = 10/group) were isolated and suspended in physiological organ baths. Human MSCs were stressed with 60-min hypoxia and conditioned media was collected. Pulmonary artery rings were treated with vehicle or MSC-conditioned (cell-free) media prior to hypoxia. Force displacement was continuously recorded. Data (mean +/- SEM) were analyzed with two-way analysis of variance with post-hoc Bonferroni test. RESULTS: Pulmonary arteries exposed to MSC-conditioned media experienced an augmented vasodilatory phase as compared to vehicle. Maximum vasodilation was 53.58 +/- 6.42% versus 39.76 +/- 4.05% for vehicle (P < 0.001). In addition, delayed, phase II vasoconstriction was significantly attenuated as compared to vehicle. Maximum phase II vasoconstriction was 28.51 +/- 12.42 versus 86.29 +/- 15.99% for vehicle (P < 0.001). CONCLUSIONS: We conclude that acute hypoxia induces HPV and that MSC-conditioned media acutely attenuates this effect. Thus, in addition to a direct contribution to vessel remodeling in chronic hypoxia, MSCs may acutely protect and attenuate hypoxic pulmonary vasoreactivity through a paracrine mechanism. PMID- 17868700 TI - Effects of progesterone on intestinal inflammatory response, mucosa structure alterations, and apoptosis following traumatic brain injury in male rats. AB - BACKGROUND: Traumatic brain injury (TBI) can induce a persistent inflammatory response, histopathological changes, and apoptosis in the gut. Progesterone given after TBI has been shown to reduce the cerebral inflammation and neuronal apoptosis in the brain. However, the effects of progesterone on the inflammatory response, structure alterations, and apoptosis in the intestinal mucosa following TBI has not been investigated. MATERIALS AND METHODS: Right parietal cortical contusion in male rats was made by using the weight-dropping method. Rats were given 0 or 16 mg/kg injections of progesterone at postinjury at 1 and 6 hours and on days 1, 2, 3, 4, and 5. Gut samples were extracted at 5 days after trauma. We measured the concentrations of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha, and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay; intercellular adhesion molecule-1 expression by immunohistochemistry; intestinal mucosal morphological changes by histopathological study and electron microscopy; and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. RESULTS: Administration of progesterone following TBI could decrease the intestinal concentrations of IL-1beta and tumor necrosis factor alpha, but not IL-6. The level of intercellular adhesion molecule-1 expression in the gut was down-regulated by progesterone. TBI-induced damages of gut structure and apoptosis were attenuated after progesterone injections. CONCLUSIONS: The results of the present study suggest that post-TBI progesterone administration could suppress the intestinal inflammation, protect the intestinal mucosal structure, and reduce the mucosa apoptosis. PMID- 17868701 TI - Molecular sex: the importance of base composition rather than homology when nucleic acids hybridize. AB - On learning that nucleic acid hybridization had been achieved in a test tube, Huxley hailed the discovery of "molecular sex." The description was apt, since sex involves recombination, which requires hybridization that, in turn, depends on a successful homology search. Conversely, when the homology search fails, recombination fails. In yeast, this failure has been attributed to "simple sequence divergence." But sequence divergence does not impair nucleic acid hybridization simply. Most natural single-stranded nucleic acids are predisposed to adopt higher-order structures containing stem-loops. Tomizawa showed that the rate-limiting step in the hybridization of single-stranded sequences is an initial "kissing" exploration between complementary loops, which must first be appropriately extruded and aligned. Successful duplex formation requires successful synchronization of matching higher-ordered structures, which depends, not so much on the degree of similarity between their base sequences as on the closeness of their base compositions (GC%). In these terms, we can understand how the anti-recombinational effect of GC% differences supports the duplication both of genes within a genome and of genomes within a genus (speciation). PMID- 17868717 TI - Optimized prostate brachytherapy minimizes the prognostic impact of percent of biopsy cores involved with adenocarcinoma. AB - PURPOSE: A higher percent of positive biopsy cores predicts poor biochemical failure-free survival. The highest dose covering at least 90% of the prostate is a standard method of measuring implant quality. We tested the hypothesis that the percentage of positive biopsy cores loses its adverse prognostic impact in patients who receive implants with a highest dose covering at least 90% of the prostate of 100% or greater of the prescription dose. MATERIALS AND METHODS: A total of 568 patients with intermediate to high risk adenocarcinoma of the prostate who were previously treated with brachytherapy in a prospective, randomized study were evaluated. The relationship between the percentage of positive biopsy cores, the highest dose covering at least 90% of the prostate and biochemical failure was examined. RESULTS: At a median followup of 50 months the rate of 5-year biochemical failure-free survival was 87% for the entire group and 92% vs 81% for patients with less than 50% vs 50% or greater positive biopsy cores (log rank p = 0.009). The mean highest dose covering at least 90% of the prostate was statistically lower in failing vs nonfailing cases (p = 0.03). Gleason score, prostate specific antigen, 50% or greater positive biopsy cores and the highest dose covering at least 90% of the prostate were the only statistically significant predictive factors for biochemical failure-free survival on multivariate Cox regression analysis. When regression analysis was restricted to the 237 patients who received implants with a highest dose covering at least 90% of the prostate of 100% or greater, 50% or greater positive biopsy cores lost predictive value but prostate specific antigen and Gleason score remained independent prognostic factors. CONCLUSIONS: A total of 50% or greater positive biopsy cores is an independent predictor of poor biochemical failure free survival in patients treated with brachytherapy. High quality prostate brachytherapy, defined by a highest dose covering at least 90% of the prostate of 100% or greater, minimize the adverse effect of 50% or greater positive biopsy cores on time to biochemical failure. PMID- 17868718 TI - Low morbidity following high dose rate brachytherapy in the setting of prior transurethral prostate resection. AB - PURPOSE: We reviewed our single institution experience with high dose rate brachytherapy in patients who underwent prior transurethral prostate resection. MATERIALS AND METHODS: A total of 28 patients treated with high dose rate brachytherapy for prostate cancer at our institution between 2001 and 2006 were identified as having undergone prior transurethral prostate resection. All patients received high dose rate brachytherapy as a boost before or after conformal external beam radiation therapy to 4,500 cGy. Boost brachytherapy doses ranged from 1,600 to 1,900 cGy, given in 2 or 3 fractions. Changes in American Urological Association symptom scores were assessed. RESULTS: Dosimetric goals were adequately achieved in all patients with a median minimal dose to 90% of the prostate of 109% of the prescription dose (range 100% to 117%). The median volume receiving 100% of the prescribed dose was 95% (range 87.9% to 100%) Three patients (11%) required temporary urinary catheter placement for acute obstructive symptoms after brachytherapy. At a median followup of 2.5 years there was 1 case each of grade 1 rectal proctitis, grade 1 hemorrhage and grade 2 cystitis. Two patients had worsening of existing grade 1 urge incontinence to grade 2. No patient had a bulbourethral stricture requiring dilation or new onset incontinence. Patients with a higher baseline American Urological Association score demonstrated significantly improved scores over those with lower baseline scores (less than 15) at least 1 year after treatment. CONCLUSIONS: High dose rate brachytherapy with careful attention to dosimetry is a reasonable treatment option for patients who have undergone prior transurethral prostate resection with the expectation of low morbidity. PMID- 17868719 TI - Validity of the CAPRA score to predict biochemical recurrence-free survival after radical prostatectomy. Results from a european multicenter survey of 1,296 patients. AB - PURPOSE: The CAPRA (Cancer of the Prostate Risk Assessment) score from the University of California, San Francisco provides a new statistical model to predict recurrence-free survival and pathological tumor stage after radical prostatectomy. It was originally developed using data from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry. To calculate the score, which ranges from 0 to 10, 5 clinical variables are needed, ie prostate specific antigen, Gleason sum, clinical tumor grade, percentage of positive biopsies and patient age. To date, the only external validation of the CAPRA score has been conducted using the SEARCH (Shared Equal Access Regional Cancer Hospital) database. The present study uses a German database to contribute to existing validation work and to test transferability of the CAPRA score to a sample that differs fundamentally from the SEARCH sample in terms of clinical features. MATERIALS AND METHODS: Data from 1,296 German patients after radical prostatectomy were used for validation. Mean followup was 56.5 (+/-35.4) months. Accuracy of prediction of recurrence-free survival and pathological tumor stage with the CAPRA score was analyzed using Kaplan-Meier analysis, proportional hazards regression, logistic regression and graphic representation. RESULTS: For the external validation of the CAPRA score, the underlying clinical variables of our study group were unfavorable compared to the original cohort from the CaPSURE data set. The recurrence-free survival rate decreased after 3 and 5 years from 100% to 97%, respectively, in the CAPRA score 0 to 1 group, and from 44% to 31%, respectively, in the CAPRA score of 7 or higher group. The hazard ratios of a biochemical recurrence per 1-group increase were 1.50 (95% CI 1.43-1.56) for the CAPRA sum score, 1.62 (95% CI 1.53-1.71) for the 7-group CAPRA score and 3.52 (95% CI 3.00-4.12) for the 3-group CAPRA score. Concordance indices between 0.78 and 0.81 suggested good predictive accuracy. Of the 5 CAPRA constituents 4 independently predicted recurrence-free survival, ie prostate specific antigen, Gleason sum, cT stage and percent of positive biopsies. Positive margins occurred in 13.1% of patients with a CAPRA score of 0 to 1 vs 62% of patients with a score of 7 to 10 (p <0.001). Organ confined tumors were present in 97.7% of patients with a CAPRA score of 0 to 1 vs 19.3% of those with a score of 7 to 10 (p <0.001). CONCLUSIONS: Despite different clinical features in the present patient cohort and the CaPSURE data set, the accuracy of the CAPRA nomogram in predicting recurrence-free survival was high. These results underscore the effectiveness and the clinical applicability of the CAPRA score which, in addition to patient counseling, may also be used for risk stratification in clinical studies. PMID- 17868720 TI - Applying population dynamics modeling to patients with lymph node positive prostate cancer. AB - PURPOSE: We previously reported the applications of population dynamics modeling on cancer populations. Cancer death populations show a reproducible progression from an essentially linear phase, in which cure is likely, through a Gompertzian phase of advancing disease to an exponential phase of incurable disease. The latter 2 phases meet at an inflection, at which the disease process becomes incurable. Patients with prostate cancer and positive lymph nodes are often considered to be doomed to distant failure. We applied these models to that population to examine whether those data support this presumption. MATERIALS AND METHODS: The public use Surveillance, Epidemiology and End Results Registry was queried for observed survival data on the population of men with nonmetastatic prostate cancer and positive lymph nodes presenting between 1988 and 1993. Lymph node data were first collated in 1988. The closing date was selected to allow a minimum 10-year followup since Surveillance, Epidemiology and End Results data are complete through 2003. These data were modeled using Gompertzian and exponential models to determine whether an inflection point exists. RESULTS: Gompertzian modeling best described the observed survival of the 2,265 patients retrieved from the Surveillance, Epidemiology and End Results Registry. Analysis of the data revealed an inflection 4 years after diagnosis. We interpreted this to indicate that there is a 4-year window during which curative therapy may be initiated in this population of patients. CONCLUSIONS: Patients with lymph node positive prostate cancer need not be considered to represent a doomed population, although new therapies are crucial in that case. We theorize that a 4-year window exists during which potentially curable therapies may be performed. PMID- 17868721 TI - Association of body mass index with response and survival in men with metastatic prostate cancer: Southwest Oncology Group trials 8894 and 9916. AB - PURPOSE: We evaluated the effect of body mass index on prostate specific antigen response, and progression-free and overall survival in men with androgen dependent or androgen independent metastatic prostate cancer. MATERIALS AND METHODS: We examined the prognostic impact of body mass index in patient cohorts from phase III randomized studies coordinated by the Southwest Oncology Group. The first study included 1,006 men treated with androgen deprivation for metastatic prostate cancer. The second study included 671 patients treated with chemotherapy for metastatic, androgen independent prostate cancer. RESULTS: Among men with androgen dependent disease, higher body mass index was associated with longer overall (p <0.001) and progression-free (p = 0.009) survival, as well as with an increased likelihood of achieving a prostate specific antigen nadir less than 4 ng/ml (p = 0.008). In multivariate analysis adjusting for risk factors, increasing body mass index was positively correlated with overall survival (p <0.01) and overweight but not obese patients (body mass index 27 to 29.9) had a significantly improved outcome compared to normal weight patients, with hazard ratios for risk of progression and death of 0.82 (95% CI 0.69, 0.98) and 0.75 (95% CI 0.63, 0.89), respectively. Among men with androgen independent prostate cancer, no clear association could be detected between body mass index and progression-free survival, overall survival or prostate specific antigen response. CONCLUSIONS: This study revealed higher body mass index to be associated with better overall and progression-free survival in patients with androgen dependent metastatic prostate cancer. Among men who had androgen independent disease, no significant association was found between body mass index and survival. PMID- 17868722 TI - Association of obesity with tumor characteristics and treatment failure of prostate cancer in African-American and European American men. AB - PURPOSE: The impact of body mass index on tumor characteristics and treatment failure in prostate cancer is not well understood in diverse ethnic groups. We evaluated the effect of body mass index in African-American and European American patients from a radical prostatectomy cohort between 1995 and 2004 with regard to tumor histopathological characteristics and biochemical relapse-free survival. MATERIALS AND METHODS: A total of 924 patients were studied to evaluate whether obese men (body mass index greater than 30) had different preoperative and postoperative tumor characteristics or biochemical relapse-free survival compared to nonobese men. There were 784 European American and 140 African-American patients analyzed using failure time models, adjusted for age, preoperative prostate specific antigen, tumor stage and race. RESULTS: Mean and median followup was 42 and 36 months, respectively. African-American men were significantly more obese than European American men. Mean body mass index was 29.0 in African-American and 28.1 in European American men (p = 0.003). African American men (OR 2.30, 95% CI 1.04-5.1) were more likely to have higher tumor stage on final pathology. Obesity was a risk factor for biochemical failure in African-American men (adjusted hazard ratio 5.49, 95% CI 2.16-13.9) but not in European American men (HR 1.41, 95% CI 0.96-2.08), and this difference was statistically significant (p value for interaction 0.036). CONCLUSIONS: Obesity is associated with poorer tumor prognostic characteristics and decreased biochemical relapse-free survival, particularly in African-American men. These data suggest that obesity may in part explain the poorer prostate cancer prognosis seen in African-American men compared to other racial and ethnic groups. PMID- 17868723 TI - Impact of patient age on biochemical recurrence rates following radical prostatectomy. AB - PURPOSE: Increased age has been suggested to predict worse clinical outcomes in patients with prostate cancer. An explanation that was proposed for this observation is that it is due to inherent differences in the biological properties of prostate cancer in older men. Stage migration, prostate specific antigen and prostate biopsy pathology are variables that may confound the interpretation of age as an independent prognosticator of outcomes following radical prostatectomy. MATERIALS AND METHODS: Matched pairs analysis was performed comparing the 3 age cohorts 46 to 55, 56 to 65 and older than 65 years to a cohort of 435 patients who were 45 years or younger based on propensity scores calculated with all known preoperative variables. Postoperative clinical and pathological characteristics were compared among the 4 matched age cohorts. A Cox hazards model was used to compare time to prostate specific antigen recurrence across the different age cohorts and the actuarial risk of recurrence was calculated using Kaplan-Meier and log rank survivor analyses. RESULTS: Younger patients showed lower grade disease (p <0.001), and lower rates of positive surgical margin rates (p = 0.035) and extraprostatic extension (p <0.001) but they did not have higher rates of lymph node involvement (p = 0.85) or seminal vesicle invasion (p = 0.56). Kaplan-Meier analysis showed no significant differences in biochemical recurrence across the age cohorts (log rank 0.38). On multivariate analysis prostatectomy Gleason score, pathological stage, positive surgical margins (each p <0.001) and preoperative prostate specific antigen (p = 0.04) were independently predictive of biochemical recurrence. CONCLUSIONS: We report that increased age is not associated with worse biochemical outcomes following radical prostatectomy and it should not be considered an independent prognosticator for disease recurrence. Rather, age is a surrogate for known predictors of biochemical recurrence following surgery. PMID- 17868724 TI - Current age and race adjusted prostate specific antigen threshold values delay diagnosis of high grade prostate cancer. AB - PURPOSE: Age specific prostate specific antigen ranges have been advocated to increase the predictive value of prostate specific antigen based on increases that occur with aging. We suggest that prostate specific antigen is not a dichotomous biomarker and age specific reference ranges delays the diagnosis of high grade prostate cancer in older and black American men. MATERIALS AND METHODS: Using the Prostate Cancer Prevention Trial risk calculator we evaluated the impact of age on the risk of high grade prostate cancer in white and black men. We created a hypothetical population of men by standardizing risk variables, including negative family history, normal digital rectal examination and no history of negative biopsy. Results were compared in the 2 populations using 5 year age increments from ages 55 to 75 years and increasing prostate specific antigen. RESULTS: Increasing age was associated with a higher risk of high grade prostate cancer in white and black men. The risk of high grade prostate cancer in a black man was twice that in a white man with the same prostate specific antigen at all prostate specific antigen values. CONCLUSIONS: Age specific and race specific prostate specific antigen ranges are flawed. Many patients who would not be considered for biopsy based on these prostate specific antigen ranges are at significant risk for high grade prostate cancer. The risk of high grade prostate cancer in black men is twice that in white men. Risk assessment in black men and older men is necessary to diagnose high grade prostate cancer when treatment can be effective. PMID- 17868725 TI - Predicting the risk of patients with biopsy Gleason score 6 to harbor a higher grade cancer. AB - PURPOSE: Prostate cancer Gleason score 3 + 3 = 6 is currently the most common score assigned on prostatic biopsies. We analyzed the clinical variables that predict the likelihood of a patient with biopsy Gleason score 6 to harbor a higher grade tumor. MATERIALS AND METHODS: The study population consisted of 448 patients with a mean age of 59.1 years who underwent radical prostatectomy between February 2003 to October 2006 for Gleason score 6 adenocarcinoma. The effect of preoperative variables on the probability of a Gleason score upgrade on final pathological evaluation was evaluated using logistic regression, and classification and regression tree analysis. RESULTS: Gleason score upgrade was found in 91 of 448 patients (20.3%). Logistic regression showed that only serum prostate specific antigen and the greatest percent of cancer in a core were significantly associated with a score upgrade (p = 0.0014 and 0.023, respectively). Classification and regression tree analysis showed that the risk of a Gleason score upgrade was 62% when serum prostate specific antigen was higher than 12 ng/ml and 18% when serum prostate specific antigen was 12 ng/ml or less. In patients with serum prostate specific antigen lower than 12 ng/ml the risk of a score upgrade could be dichotomized at a greatest percent of cancer in a core of 5%. The risk was 22.6% and 10.5% when the greatest percent of cancer in a core was higher than 5% and 5% or lower, respectively. CONCLUSIONS: The probability of patients with a prostate biopsy Gleason score of 6 to conceal a Gleason score of 7 or higher can be predicted using serum prostate specific antigen and the greatest percent of cancer in a core. With these parameters it is possible to predict upgrade rates as high as 62% and as low as 10.5%. PMID- 17868726 TI - Prostate cancer risk assessment program: a 10-year update of cancer detection. AB - PURPOSE: Guidelines for screening men at high risk for prostate cancer remain under investigation. We report our 10-year cancer detection data from the Prostate Cancer Risk Assessment Program, a longitudinal screening program for men at high risk. MATERIALS AND METHODS: Men between ages 35 and 69 years with a family history of prostate cancer, any black man regardless of family history or any patient with a known mutation in the BRCA 1 gene are eligible for the Prostate Cancer Risk Assessment Program and undergo longitudinal followup. Cancer detection, prostate cancer features and the predictive value of screening parameters were determined based on Prostate Cancer Risk Assessment Program biopsy criteria. RESULTS: A total of 609 men were accrued to the Prostate Cancer Risk Assessment Program as of the end of June 2006, of whom 61.2% were black. Of all participants 19% underwent prostate biopsies. The prostate cancer incidence was 9.0%, more than 90% of prostate cancers were Gleason score 6 or higher and 22% were Gleason score 7 or higher. The majority were organ confined. Of men diagnosed with prostate cancer 20% had a prostate specific antigen of less than 2.5 ng/ml and a free prostate specific antigen of less than 25% with a normal digital rectal examination. CONCLUSIONS: Our results support aggressive screening measures for men at high risk for prostate cancer. The majority of cancers detected were at a prostate specific antigen of less than 4.0 ng/ml with a fifth diagnosed at a prostate specific antigen of below 2.5 ng/ml. These cancers were intermediate to high grade and organ confined, indicating a greater likelihood of cure following local therapy in these men. PMID- 17868727 TI - Interleukin-6/10 ratio as a prognostic marker of recurrence in patients with intermediate risk urothelial bladder carcinoma. AB - PURPOSE: Several potential markers have been investigated to improve the noninvasive diagnosis of recurrent superficial bladder carcinoma. We evaluated the role of the interleukin-6/10 ratio as a prognostic marker of recurrence in patients with intermediate risk superficial bladder carcinoma. MATERIALS AND METHODS: A total of 65 consecutive urological patients seen in the office, including 41 with intermediate risk superficial bladder carcinoma and 24 controls, were selected for this prospective study. Five urine samples for urinary cytology and interleukin analyses were collected from each subject at baseline, and 3, 6, 9 and 12 months after surgery, respectively. Interleukin-6 and 10 were determined in urine by the Quantikine solid phase interleukin-6 and 10 enzyme-linked immunosorbent assay, respectively. Sensitivity, specificity, and positive and negative predictive values of the method were calculated. RESULTS: At baseline sample collection the interleukin-6/10 ratio was not statistically different between patients and controls (p = 0.58). Interleukin-6/10 was statistically different between patients with vs without recurrence 3 (0.009 vs 0.408), 6 (0.011 vs 0.268), 9 (0.012 vs 0.288) and 12 months (0.009 vs 0.302) after pre-transurethral bladder tumor resection (each p <0.001). Multivariate analysis indicated that interleukin-6/10 was an independent prognostic factor of recurrence (HR 3.62, 95% CI 2.80-4.92, p <0.001). Test sensitivity and specificity were 0.83% (95% CI 0.57-0.95) and 0.76% (95% CI 0.45-0.93), respectively. CONCLUSIONS: The current study highlights the feasible role of the interleukin-6/10 ratio for predicting intermediate risk superficial bladder carcinoma recurrence. However, clinical trials with a greater number of patients are needed to consider its use in clinical urological practice. PMID- 17868728 TI - Prognostic factors of metastatic renal cell carcinoma after failure of immunotherapy: new paradigm from a large phase III trial with shark cartilage extract AE 941. AB - PURPOSE: We analyzed prognostic factors, described survival and generated a prognostic model in patients with metastatic renal cell carcinoma in whom immunotherapy failed and who were potentially eligible for novel agents. MATERIALS AND METHODS: An analysis of the relationship between clinical features and survival was performed in 300 patients with advanced renal cell carcinoma in whom immunotherapy had failed and who were subsequently treated as part of a single, phase III clinical trial with the anti-angiogenic agent Neovastat (shark cartilage extract AE 941). Clinical features were first examined univariately and a stepwise modeling approach based on Cox proportional hazard regression was then performed to generate a multivariate model. RESULTS: Median and progression-free survival (prognostic factors) for the whole cohort was 12.6 and 2 months, respectively. Prognostic features associated with shorter survival on multivariate analysis were the number of metastatic sites (greater than 1), time from nephrectomy to metastatic disease (less than 2 years), high alkaline phosphatase, abnormal corrected serum Ca and high lactate dehydrogenase (greater than 1.5 x the upper limit of normal). Four prognostic subgroups were identified by counting the number of adverse prognostic factors. Median survival in patients with zero adverse prognostic factors was 15.6 months compared to 11.7 months in patients with 1, 8.5 months in patients with 2 and 3.5 months in patients with 3 or more. CONCLUSIONS: We identified 4 risk groups to predict survival in previously treated patients with renal cell carcinoma. This model was based on data from what is to our knowledge the largest experience in this population. It should be used in clinical trial design, risk stratification and patient counseling. PMID- 17868729 TI - Cytoreductive nephrectomy for metastatic renal cell carcinoma with nonclear cell histology. AB - PURPOSE: To our knowledge the benefit of cytoreductive surgery for patients with metastatic renal cell carcinoma with nonclear cell histology is unknown. In this retrospective study we report our experience with cytoreductive nephrectomy for nonclear cell metastatic renal cell carcinoma at M. D. Anderson Cancer Center. We compared the outcomes with those in patients with clear cell metastatic renal cell carcinoma. MATERIALS AND METHODS: From 1991 to 2006, 606 patients with metastatic renal cell carcinoma underwent cytoreductive nephrectomy and they formed the basis of this report. Of these patients 92 had nonclear cell metastatic renal cell carcinoma. The remaining 514 patients had clear cell metastatic renal cell carcinoma and they formed a comparative group. Multivariate Cox regression analysis was performed to evaluate the relationship between clinical variables and histology (clear cell vs nonclear cell) on disease specific survival. RESULTS: Compared with patients with clear cell histology those with nonclear cell metastatic renal cell carcinoma were younger (p = 0.0001), and more likely to have nodal metastases (p <0.0001) and sarcomatoid features (23% vs 13%, p = 0.026). On multivariate analysis median disease specific survival in patients with nonclear cell histology was significantly worse than that in patients with clear cell metastatic renal cell carcinoma (9.7 vs 20.3 months, p = 0.0003) even after adjusting for T stage, grade, performance status, age and sarcomatoid features. Sarcomatoid features were a predictor of poor outcome in cases of clear and nonclear cell histology, although even in the absence of sarcomatoid features nonclear cell histology was associated with worse disease specific survival (p = 0.017). Interestingly although there was a significantly higher incidence of positive nodes in patients with nonclear histology (p <0.0001), this phenotype was not associated with a worse disease specific survival, as it was in those with clear cell histology (p = 0.0001). In fact, patients with node negative disease with nonclear cell histology had the worst prognosis overall in the entire group. CONCLUSIONS: Patients with nonclear cell metastatic renal cell carcinoma were younger and had a higher incidence of nodal metastases, a higher incidence of sarcomatoid features and a worse prognosis than those with clear cell histology who underwent cytoreductive surgery. PMID- 17868730 TI - The prevalence of malignancy in satellite renal lesions and its surgical implication during nephron sparing surgery. AB - PURPOSE: We examined the prevalence of malignancy in a synchronous ipsilateral renal lesion identified during partial nephrectomy and evaluated its clinical significance. MATERIALS AND METHODS: We retrospectively reviewed the records of 112 patients (114 renal units) who underwent nephron sparing surgery for a clinically localized sporadic renal mass between May 1995 and September 2005. RESULTS: In 37 patients (32%) an additional lesion was diagnosed and excised intraoperatively, while in 67% these lesions were known before the operation and believed to be simple cysts. During surgery the additional mass was suspicious in 8 cases and in the remainder the mass was described as simple cysts that were excised. The mean size of the primary mass was 3.1 cm (SD 1.4). In 29 (78%) cases the primary mass was malignant, in 23 (79%) of these the second mass was benign and in the remainder renal cell carcinoma was diagnosed. In 8 cases (22%) the primary mass was benign and in 2 (25%) the secondary mass was malignant. Overall 22% of all second masses were malignant, and all were low grade and low stage. We found that 7% of second ipsilateral masses could be expected to harbor malignancy. CONCLUSIONS: Based on our data it is questionable whether total nephrectomy is mandatory as an immediate response to an ipsilateral synchronous second renal mass. The present findings may represent an increased appreciation of ipsilateral multicentricity compared to historical data. PMID- 17868731 TI - Prospective radiographic followup after en bloc ligation of the renal hilum. AB - PURPOSE: We determined the risk of arteriovenous fistula after en bloc ligation of the renal hilum. MATERIALS AND METHODS: A prospective evaluation of all patients who underwent en bloc ligation of the renal hilum during nephrectomy for malignant disease was performed. Pertinent operative data were recorded and patients were followed for clinical evidence of arteriovenous fistula formation, including hypertension, abdominal bruit and new onset congestive heart failure. Patients with at least 12 months of followup underwent computerized tomographic arteriography to assess arteriovenous fistula formation. RESULTS: A total of 94 patients underwent en bloc renal hilar ligation during open (43) and laparoscopic (51) nephrectomy using a 45 mm titanium endovascular stapler. Of this cohort 11 patients were lost to followup and 3 died of disease. The remaining 80 patients were followed an average of 35.2 months with no clinical evidence of arteriovenous fistula formation. Specifically there was no statistically significant difference in preoperative and postoperative blood pressure (p = 0.18 and 0.62, respectively), no evidence of abdominal bruit on examination and no new onset congestive heart failure. A total of 32 had increased serum creatinine and, therefore, they were excluded from followup computerized tomographic arteriography. Eight patients had a followup of less than 1 year and they were not yet eligible for evaluation. In the 40 patients who underwent computerized tomographic arteriography no fistulas were noted. CONCLUSIONS: Based on clinical followup and prospective radiographic evaluation there appears to be a low risk of arteriovenous fistula formation after en bloc ligation of the renal hilum using a titanium endovascular stapler. PMID- 17868732 TI - Sunitinib efficacy against advanced renal cell carcinoma. AB - PURPOSE: We assessed the efficacy of the oral multitargeted tyrosine kinase inhibitor sunitinib in patients with metastatic clear cell renal cell carcinoma. MATERIALS AND METHODS: Patients with metastatic clear cell renal cell carcinoma were enrolled in this multicenter, phase II clinical trial. Major eligibility requirements were clear cell renal cell carcinoma histology, prior nephrectomy, measurable metastases and failed prior cytokine therapy as a result of disease progression. Sunitinib was given orally as second line therapy in 6-week cycles of 50 mg daily for 4 weeks, followed by 2 weeks off drug per treatment cycle. Response to sunitinib was rigorously assessed by an independent third party core imaging laboratory (central review). RESULTS: Of 106 patients enrolled in the study 105 were evaluated for response. As determined by independent third party assessment, the objective response rate was 33% (95% CI 24%-43%) with a median response duration of 14.0 months. Median time to progression and median progression-free survival in the 105 evaluable patients was 10.7 and 8.8 months, respectively. Median survival was 23.9 months and 43 patients remained alive at a median followup of 29.7 months. CONCLUSIONS: The results of this trial demonstrate the efficacy of sunitinib for metastatic renal cell carcinoma. The optimal integration of surgery and sunitinib treatment requires further prospective investigation. PMID- 17868733 TI - Location of extrarenal tumor extension does not impact survival of patients with pT3a renal cell carcinoma. AB - PURPOSE: The current TNM classification for pathological pT3a renal cell carcinoma includes patients with perinephric or sinus fat invasion, suggesting that the prognoses are similar for these pathological findings. However, sinus fat invasion was proposed by some investigators to be an independent predictor of inferior cancer specific outcome following surgical treatment. To assess and improve the predictive ability of the current pT3a primary tumor classification we evaluated the prognostic significance of location of extrarenal tumor extension on cancer specific survival following surgery. MATERIALS AND METHODS: The database of 3,470 patients at our institution who were treated for renal cell carcinoma from 1990 to 2006 was searched for those with pT3a tumors managed by partial or radical nephrectomy. Patients with nonrenal cell carcinoma histology, direct adrenal invasion or a followup of less then 6 months were excluded from analyses. The prognostic importance of all clinical and pathological variables was investigated using Cox proportional hazards regression. RESULTS: A total of 365 patients with pT3a renal cell carcinoma and a mean followup of 33.5 months (range 6.1 to 158.6) met study inclusion criteria and they comprise the data set for this analysis. There was no difference in 5-year cancer specific survival between 166 patients (45.5%) with SF invasion and 199 (54.5%) with PF invasion only (50.8% and 54.1%, p = 0.782 respectively). On univariate analyses neither sinus fat invasion nor the location of extrarenal extension, assessed as perinephric fat vs sinus fat vs perinephric plus sinus fat, correlated with cancer specific survival following surgical treatment (HR 1.052, p = 0.783 and HR 1.072, p = 0.543, respectively). After adjusting for the effects of nodal and systemic metastases tumor grade and sarcomatoid differentiation remained independent predictors of renal cell carcinoma specific survival in our pT3a cohort of patients (HR 1.508, p = 0.003 and HR 1.810, p = 0.018, respectively). CONCLUSIONS: In contrast to previously reported observations, in our cohort of surgically treated patients with pT3a renal cell carcinoma the location of extrarenal extension was not an important prognosticator of cancer specific mortality. Based on our findings we confirm that perinephric and/or sinus fat should be similarly subclassified in the primary tumor staging system. PMID- 17868734 TI - Elisabeth Pauline Pickett (1918-): opening the door for women in urological oncology. AB - PURPOSE: We outline the career of Elisabeth Pauline Pickett (1918-), the first board certified female urologist. MATERIALS AND METHODS: The historical literature including personal writings of Pickett and her mentors were reviewed. The factors which determine female medical student career choice as well as a summary of the current status of women in urology were also examined. RESULTS: The groundwork for women in the modern era of urology was forged by Mary E. Childs MacGregor, who also supported and encouraged fellowship training. Inspired by Doctor MacGregor's example, Elisabeth Pickett became the first female general surgeon to complete a fellowship in urological oncology in 1955 under Dr. Willet Whitmore at Memorial Sloan-Kettering, and to be board certified in urology in 1962. Despite the benchmark set by these early pioneers the American Board of Urology currently lists only 324 female board certified urologists, 86 female candidates and 20 board eligible individuals as of the year 2006. CONCLUSIONS: Although the number of female graduating medical students in modern times is equivalent to males, there still exists a large discrepancy in the number of women choosing urology and other surgical subspecialties as a career. Elisabeth Pickett demonstrated that it could be done at a time when few thought it possible. However, only a minority of women today continue to pursue fellowship training. PMID- 17868735 TI - Decision analysis and Markov modeling in urology. AB - PURPOSE: The process of decision making in medicine has become increasingly complex. This has developed as the result of increasing amounts of data, often without direct information or answers regarding a specific clinical problem. The use of mathematical models has grown and they are commonly used in all areas. We describe and discuss the application of decision analysis and Markov modeling in urology. MATERIALS AND METHODS: We define decision analysis and Markov models, providing a background and primer to educate the urologist. In addition, we performed a complete MEDLINE database search for all decision analyses in all disciplines of urology, serving as a reference summarizing the current status of the literature. RESULTS: The review provides urologists with the ability to critically evaluate studies involving decision analysis and Markov models. We identified 107 publications using decision analysis or Markov modeling in urology. A total of 36 studies used Markov models, whereas the remainder used standard decision analytical models. All areas of urology, including oncology, pediatrics, andrology, endourology, reconstruction, transplantation and erectile dysfunction, were represented. CONCLUSIONS: Decision analysis and Markov modeling are widely used approaches in the urological literature. Understanding the fundamentals of these tools is critical to the practicing urologist. PMID- 17868736 TI - Open versus laparoscopic live donor nephrectomy: a focus on the safety of donors and the need for a donor registry. AB - PURPOSE: A review of the existing literature showed that the subject of live donor nephrectomy is a seat of underreporting and underestimation of complications. We provide a systematic comparison between laparoscopic and open live donor nephrectomy with special emphasis on the safety of donors and grafts. MATERIALS AND METHODS: The PubMed literature database was searched from inception to October 2006. A comparison was made between laparoscopic and open live donor nephrectomy regarding donor safety and graft efficacy. RESULTS: The review included 69 studies. There were 7 randomized controlled trials, 5 prospective nonrandomized studies, 22 retrospective controlled studies, 26 large (greater than 100 donors), retrospective, noncontrolled studies, 8 case reports and 1 experimental study. Most investigators concluded that, compared to open live donor nephrectomy, laparoscopic live donor nephrectomy provides equal graft function, an equal rejection rate, equal urological complications, and equal patient and graft survival. Analgesic requirements, pain data, hospital stay and time to return to work are significantly in favor of the laparoscopic procedure. On the other hand, laparoscopic live donor nephrectomy has the disadvantages of increased operative time, increased warm ischemia time and increased major complications requiring reoperation. In terms of donor safety at least 8 perioperative deaths were recorded after laparoscopic live donor nephrectomy. These perioperative deaths were not documented in recent review articles. Ten perioperative deaths were reported with open live donor nephrectomy by 1991. No perioperative mortalities have been recorded following open live donor nephrectomy since 1991. Regarding graft safety, at least 15 graft losses directly related to the surgical technique of laparoscopic live donor nephrectomy were found but none was emphasized in recent review articles. The incidence of graft loss due to technical reasons in the early reports of open live donor nephrectomy was not properly documented in the literature. CONCLUSIONS: We are in need of a live organ donor registry to determine the combined experience of complications and long-term outcomes, rather than short-term reports from single institutions. Like all other new techniques, laparoscopic live donor nephrectomy should be developed and improved at a few centers of excellence to avoid the loss of a donor or a graft. PMID- 17868737 TI - Vaginal substitution: attempts to create the ideal replacement. AB - PURPOSE: Vaginal substitution may be necessary for vaginal agenesis (Mayer Rokitansky-Kuster-Hauser syndrome), cloacal anomalies and certain intersex disorders or following pelvic exenterative surgery. The ideal method of vaginal replacement should provide a cosmetically acceptable, low maintenance vaginal substitute with minimal morbidity and excellent long-term function. We present the available literature on the various approaches to vaginal substitution, focusing on outcomes, complications and long-term durability in terms of sexual function. MATERIALS AND METHODS: We performed an extensive search of the medical literature for nonoperative and operative alternatives for vaginal replacement. We focused on surgical indications, complications, long-term sexual function if available, and inherent advantages and disadvantages of the specified technique. RESULTS: Popular methods of vaginal substitution include passive dilation, inlay skin grafts, rotational myocutaneous flaps and bowel substitute vaginoplasty. These methods have been modified to some extent, and carry inherent advantages and disadvantages. Reports in the literature show the inherent biases of the proponents of different methods. CONCLUSIONS: There are many options for vaginoplasty. The ideal method is not currently known and depends on numerous factors including patient preparedness, surgeon experience, and patient and surgeon preference. Despite these issues, patients must be provided with nonoperative and operative options that address individual patient expectations, potential complications, long-term durability and long-term sexual function. PMID- 17868738 TI - Novel targeted pro-apoptotic agents for the treatment of prostate cancer. AB - PURPOSE: We reviewed and highlighted novel targeted apoptotic mediated therapies that can be used to treat prostate cancer. MATERIALS AND METHODS: A comprehensive review of the peer reviewed literature in the area of apoptosis was performed with special emphasis on apoptotic mediated pathways with promising novel targeted therapies that can be used for patients with prostate cancer. RESULTS: The apoptotic pathway can be classified into 2 separate broad categories, including the extrinsic and the intrinsic pathways. Targeting the extrinsic or intrinsic mediated pathway holds promise for developing novel agents for treating prostate cancer. We discuss apoptosis related molecules and therapies, as categorized by 1) targeting apoptosis pathway for antitumor treatment, 2) targeting apoptosis regulators for antitumor treatment and 3) drugs that potentiate pro-apoptotic agents. CONCLUSIONS: Defining the molecules responsible for apoptosis and their intricate molecular interactions will help guide us in developing drugs with less toxicity for appropriately selected patients with prostate cancer and other malignancies. Because neoadjuvant and adjuvant clinical trials are under way using novel pro-apoptotic agents for prostate cancer, it is imperative for urologists to be active members of the clinical research team and become familiar with the molecular pathways, and potential benefits and toxicities associated with these novel agents. PMID- 17868739 TI - Neuromodulation and the urinary tract--are we over the rainbow or have we simply stepped through the looking glass? PMID- 17868740 TI - Obesity and prostate cancer: importance of race and stage of disease. PMID- 17868741 TI - Bacillus Calmette-Guerin mechanism of action: the role of immunity, apoptosis, necrosis and autophagy. PMID- 17868742 TI - Identification of five human novel genes associated with cell proliferation by cell-based screening from an expressed cDNA ORF library. AB - The development of functional profiling technologies provides opportunity for high-throughput functional genomics studies. We describe a cell-based screening system to identify novel human genes associated with cell proliferation. The method integrates luciferase reporter gene activity, fluorescence stain, automated microscopy and cellular phenotype assays. We successfully used the system to screen 409 novel human genes cloned by our lab and found that 27 genes significantly up-regulated promoter-Renilla luciferase reporter plasmid (pRL) activity. Among them, five genes, TRAF3IP3, ZNF306, ZNF250, SGOL1, and ZNF434, were determined through morphological observation, calcein AM fluorescence stain, MTT assay and cell cycle analysis to be associated with cell proliferation. Furthermore, we showed that the gene TRAF3IP3, which initially was identified to specifically interact with TRAF3, stimulated cell growth by modulating the c-Jun N-terminal kinase (JNK) pathway, and RNAi of TRAF3IP3 confirmed that the effect was physiological and necessary. In summary, we integrated a rapid and efficient system for screening novel growth regulatory genes. Using the new screening system we identified five genes associated with cell proliferation for the first time. PMID- 17868743 TI - Benthic indicators: analysis of the threshold values of ecological quality classifications for transitional waters. AB - The effect of the modifications of the threshold values generally adopted for the five EcoQ (Ecological Quality) classes recognized by the European Water Framework Directive (WFD) for the most used benthic indicators and diversity indicators (AMBI, BENTIX, BOPA, BQI, H', ITI and M-AMBI) were studied to test whether it is possible to obtain the same or similar ecological classifications for transitional waters using these different indicators, and determine whether the current classifications can be improved. The analysis included: (i) the use of indicator equations, (ii) the use of reference indicators, and (iii) the use of indicator distribution laws. These investigations demonstrated that it was impossible to obtain an exact intercalibration of the ecological classifications with the selected indicators. However, some propositions to improve the actual classification were suggested. PMID- 17868744 TI - The impact of organic pollution on the macrobenthic fauna of Dubai Creek (UAE). AB - Dubai Creek is a tidal marine intrusion bisecting Dubai within the United Arab Emirates (UAE). The creek extends 14km inland from its opening into the Arabian Gulf, with a narrow lower creek channel leading to a lagoon section in the upper creek. The creek contains numerous sources of organic pollution including sewage outlet flows and boat waste. A survey of the creek was performed, assessing organic pollution, water properties, and the benthic macrofaunal community. The upper creek was heavily polluted with macrofauna communities commonly associated with organic pollution and eutrophication, while the lower creek contained low pollution and relatively healthy macrofauna communities. There is little net tidal flow of water within the creek and residence time in the lagoon is high, which may account for the high organic pollution levels. However, some evidence of the pollution effect moving into the lower creek was found. The results are considered in light of current and historic organic loading within the creek and future developments in the area. PMID- 17868745 TI - Benthic meiofauna community composition at polluted and non-polluted sites in New Zealand intertidal environments. AB - Meiofauna composition was investigated for six field sites, including polluted and non-polluted sites, within two regions (Auckland and Bay of Plenty) during winter (July-August 2004) in the North Island of New Zealand. Physico-chemical parameters were measured during the sampling period and meiofauna distribution and abundance were compared with these measured parameters. Analysis of meiofauna abundance indicated that foraminiferans, nematodes and ostracods were the taxa that contributed to the variability between field sites within the Auckland region. However, no clear taxa dominance was seen in the Bay of Plenty region. Comparison of meiofauna abundance and physico-chemical parameters was done using multivariate analysis (PRIMER). However, no clear relationships between the parameters were observed in any field site in either region. The Shannon-Weiner index of diversity did not show any clear differentiation between polluted and non-polluted field sites. Therefore, from the present study, the taxa or physico chemical parameters used could not effectively characterise pollution at the investigated field sites. PMID- 17868746 TI - Microvascular blood flow and oxygenation during hemorrhagic hypotension. AB - Understanding microvascular oxygen transport requires the knowledge of microvessel topology and geometry, blood flow and oxygen levels. Microvascular hemodynamic responses to hemorrhagic hypotension (HH) such as size-dependent vasoconstriction and blood flow reduction could lead to increased longitudinal oxygen partial pressure (PO(2)) gradients. However, the mesenteric microvascular PO(2) has never been evaluated during HH. Therefore, we studied hemodynamic variables and PO(2) distribution in 165 mesenteric microvessels from 39 anesthetized rats to investigate whether HH-induced vasoconstriction and blood flow reduction were associated with changes in longitudinal PO(2) gradients. Vessels were analyzed according to their position in the network, as well as a few interstitial PO(2) areas. We found that during baseline a small PO(2) gradient exists, but HH is accompanied by more pronounced microvascular longitudinal PO(2) gradients. Decreased blood flow did not seem to completely explain these findings, since blood flow was uniformly diminished in arterioles and venules, independent of diameter and position in the network. During HH, some microvessels presented higher PO(2) than during baseline despite blood flow reduction, possibly due to a combination of systemic hyperoxia and low oxygen consumption of mesentery. The data suggest that blood flow measurements may be a poor indicator of the oxygenation status in some regions of the mesentery. The enhanced mesenteric longitudinal PO(2) gradient may lead to regions with different levels of other physiologically active compounds. PMID- 17868747 TI - Novel complex genomic rearrangement of the BRCA1 gene. AB - Initial BRCA1 and BRCA2 analyses conducted in breast and ovarian cancer families were focused on identification of mutations in coding sequences and splicing sites of the genes. Large genomic rearrangements as well as mutations in promoter or untranslated regions have been missed by standard detection strategies. Nevertheless, in Western countries, a detailed study of families with strong linkage to BRCA1 identified large genomic deletions and rearrangements in this gene as early as 1997. To date, no such gene alteration has been described in Central and Eastern European populations. In our study of BRCA1/2 genes in the Czech population, we have detected a complex genomic rearrangement in BRCA1 using RNA-based analysis for mutation screening. This rearrangement involves exons 21 and 22 and results in a protein product lacking BRCT domain important for its function. PMID- 17868749 TI - Point mutation in the NF2 gene of HEI-193 human schwannoma cells results in the expression of a merlin isoform with attenuated growth suppressive activity. AB - Neurofibromatosis type 2 (NF2) is a genetic disorder characterized by the formation of bilateral schwannomas of the eighth cranial nerve. Although the protein product of the NF2 gene (merlin) is a classical tumor suppressor, the mechanism by which merlin suppresses cell proliferation is not fully understood. The availability of isolated tumor cells would facilitate a better understanding of the molecular function of merlin, but primary schwannoma cells obtained from patients grow slowly and do not yield adequate numbers for biochemical analysis. In this study, we have examined the NF2 mutation in HEI-193 cells, an immortalized cell line derived from the schwannoma of an NF2 patient. Previous work showed that the NF2 mutation in HEI-193 cells causes a splicing defect in the NF2 transcript. We have confirmed this result and further identified the resultant protein product as an isoform of merlin previously designated as isoform 3. The level of isoform 3 proteins in HEI-193 cells is comparable to the levels of merlin isoforms 1 and 2 in normal human Schwann cells and several other immortalized cell lines. In contrast to many mutant forms of merlin, isoform 3 is as resistant to proteasomal degradation as isoforms 1 and 2 and can interact with each of these isoforms in vivo. Cell proliferation assays showed that, in NF2(-/ ) mouse embryonic fibroblasts, exogenously expressed merlin isoform 3 does exhibit growth suppressive activity although it is significantly lower than that of identically expressed merlin isoform 1. These results indicate that, although HEI-193 cells have undetectable levels of merlin isoforms 1 and 2, they are, in fact, not a merlin-null model because they express the moderately active growth suppressive merlin isoform 3. PMID- 17868748 TI - Mutagenic potential of DNA-peptide crosslinks mediated by acrolein-derived DNA adducts. AB - Current data suggest that DNA-peptide crosslinks are formed in cellular DNA as likely intermediates in the repair of DNA-protein crosslinks. In addition, a number of naturally occurring peptides are known to efficiently conjugate with DNA, particularly through the formation of Schiff-base complexes at aldehydic DNA adducts and abasic DNA sites. Since the potential role of DNA-peptide crosslinks in promoting mutagenesis is not well elucidated, here we report on the mutagenic properties of Schiff-base-mediated DNA-peptide crosslinks in mammalian cells. Site-specific DNA-peptide crosslinks were generated by covalently trapping a lysine-tryptophan-lysine-lysine peptide to the N(6) position of deoxyadenosine (dA) or the N(2) position of deoxyguanosine (dG) via the aldehydic forms of acrolein-derived DNA adducts (gamma-hydroxypropano-dA or gamma-hydroxypropano-dG, respectively). In order to evaluate the potential of DNA-peptide crosslinks to promote mutagenesis, we inserted the modified oligodeoxynucleotides into a single stranded pMS2 shuttle vector, replicated these vectors in simian kidney (COS-7) cells and tested the progeny DNAs for mutations. Mutagenic analyses revealed that at the site of modification, the gamma-hydroxypropano-dA-mediated crosslink induced mutations at only approximately 0.4%. In contrast, replication bypass of the gamma-hydroxypropano-dG-mediated crosslink resulted in mutations at the site of modification at an overall frequency of approximately 8.4%. Among the types of mutations observed, single base substitutions were most common, with a prevalence of G to T transversions. Interestingly, while covalent attachment of lysine tryptophan-lysine-lysine at gamma-hydroxypropano-dG caused an increase in mutation frequencies relative to gamma-hydroxypropano-dG, similar modification of gamma-hydroxypropano-dA resulted in decreased levels of mutations. Thus, certain DNA-peptide crosslinks can be mutagenic, and their potential to cause mutations depends on the site of peptide attachment. We propose that in order to avoid error-prone replication, proteolytic degradation of proteins covalently attached to DNA and subsequent steps of DNA repair should be tightly coordinated. PMID- 17868750 TI - GABA(B) receptor activation inhibits dopamine D1 receptor-mediated facilitation of [(3)H]GABA release in substantia nigra pars reticulata. AB - GABA(B) receptors inhibit and dopamine D1 receptors stimulate the release of GABA from striatal terminals in the pars reticulata of the substantia nigra. Here we have studied the interaction between both classes of receptors by exploring the effect of GABA(B) receptors upon the stimulation of depolarization-induced [(3)H]GABA release induced by the activation of D1 receptors in slices of the pars reticulata of the rat substantia nigra. The activation of GABA(B) receptors with baclofen (100 microM) inhibited by 48+/-8% the evoked [(3)H]GABA release in normal slices but did not modify the release in slices from reserpine-treated rats, indicating that the inhibition was dependent on endogenous dopamine. The inhibitory effect of baclofen was also abolished by the D1 receptor antagonist SCH 23390 (1 microM), indicating a D1 receptor-dependence of the baclofen inhibition. Baclofen dose-dependently inhibited (IC(50)=3.6 microM) the stimulation of release induced by the D1 agonist SKF 38393 (1 microM). Baclofen also blocked the stimulation of release induced by forskolin but not that induced by 8-Br-cAMP, indicating that the inhibitory effect was exerted before cAMP synthesis. N-ethylmaleimide (NEM), a selective inactivator of PTX-sensitive G proteins, abolished the baclofen inhibition of the SKF 38393-induced stimulation of the release without affecting the stimulation induced by the D1 agonist, suggesting that the baclofen effect was mediated by Galpha(i/o) proteins. These results might have relevance in the control motor disorders associated with D1 receptor supersensitivity. PMID- 17868751 TI - Cortisol and behavioral responses of working dogs to environmental challenges. AB - This paper's primary objective is to analyse the physiological (cortisol) and behavioral responses of military working dogs (MWD). Dogs (N=27) were submitted twice to environmental challenges (challenge 1 and 2, 20 days in-between) composed of social (training), visual (mobile toy car) and auditory (air blast) stimuli. Cortisol levels decreased back to the baseline after the second challenge. The behavioral observations showed that these MWD were more active, and presented less stereotypic behaviors (pacing, manipulation of the environment) during both visual challenges, whereas half low posture was observed during the first but not during the second visual challenge. The present study shows that this group of MWD still has an adaptation capacity to an environmental challenge (return to baseline of the cortisol levels, a higher posture during the second than at the first challenge). These results are encouraging and indicate that the dogs might have a diminished welfare (i.e. stereotypic behaviors), but are not chronically stressed. PMID- 17868752 TI - Inhibitory effect of phytoglycoprotein on tumor necrosis factor-alpha and interleukin-6 at initiation stage of colon cancer in 1,2-dimethylhydrazine treated ICR mice. AB - This study was carried out to investigate the chemopreventive potentials of plant originated glycoprotein (UDN glycoprotein, 116 kDa) isolated from the stems of Ulmus davidiana Nakai (UDN) on aberrant crypt foci (ACF) formation in 1,2 dimethylhydrazine (DMH)-treated ICR mice. UDN glycoprotein was administered to mice at 0.01% and 0.02% levels for 5 weeks. The mice were treated with 20 mg/kg DMH twice a week for 2 weeks in presence of UDN glycoprotein and killed at week 6. We found that UDN glycoprotein has inhibitory effects on the frequency of colonic aberrant crypt foci (ACF), activation of colonic proliferating cell nuclear antigen (PCNA), and release of plasma lactate dehydrogenase (LDH) in DMH treated mice. In addition, UDN glycoprotein has anti-oxidative effects on the formation of plasma thiobarbituric acid reactive substances (TBARS) and the production of plasma inducible nitric oxide (NO) in DMH-treated mouse. Also, 0.02% UDN glycoprotein suppressed the DNA binding activities of nuclear factor kappa B (NF-kappaB) and activator protein-1 (AP-1), accompanying the inhibitions of its subunits (p50, p65, c-Jun, and c-Fos), pro-inflammatory proteins [inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)], and pro inflammatory cytokines [tumor necrosis factor (TNF)-alpha and interleukin (IL)-6] on DMH-stimulated ACF formation. On the basis of these results, we assume that UDN glycoprotein may be useful for colon cancer prevention at initiation stage. PMID- 17868753 TI - Tityus perijanensis Gonzalez-Sponga (Scorpiones, Buthidae): molecular assessment of its geographical distribution and venom lethality of Venezuelan populations. AB - An extensive field survey allowed us to expand the geographical distribution of the scorpion Tityus perijanensis in the Perija range, western Zulia State, Venezuela, including areas where adult cases of severe scorpionism have been reported. 16S ribosomal RNA (rRNA) gene sequencing, DL(50) determination, and native PAGE suggest low genetic and venom proteomic divergence across the distribution range. The results also indicate phylogenetic divergence between T. perijanensis and T. discrepans, the species prevalent in northcentral Venezuela. T. perijanensis venom lethality (0.91-0.94 mg/kg) is comparable to that of the Brazilian T. serrulatus and ranks highest among toxic Venezuelan Tityus studied so far. The data indicate that the Perija range should be included amongst the endemic areas of scorpionism of Venezuela and Colombia. PMID- 17868755 TI - Attention deficit/hyperactivity disorder in adults. AB - Attention deficit/hyperactivity disorder (ADHD), characterized by inattention, hyperactivity/impulsivity, or a combination of these, is being increasingly recognized in adults. Adult ADHD prevalence rates range from 1% to 4%. The pathophysiology of adult ADHD is likely multifactorial, including genetic, environmental, and neurobiological influences. Though ADHD diagnostic criteria per the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) were developed based on child samples, the symptoms are believed to be similar in adults, with some developmental differences in symptom presentation. This article identifies common presenting complaints of adults who have ADHD and provides information useful for differential diagnosis of these patients. Specific strategies for pharmacological and nonpharmacological intervention are also presented. PMID- 17868756 TI - Recent advances in the understanding and treatment of anxiety disorders. AB - Anxiety disorders usually are chronic or recurrent disorders characterized by stress sensitivity and a fluctuating course. Both psychopharmacologic and cognitive-behavioral treatments are well-established, evidence-based treatments for panic disorder, social anxiety disorder, generalized anxiety disorder, and obsessive-compulsive disorder. Exposure-based behavioral treatment is well established as evidence-based treatment for specific phobias. Primary care physicians can make a significant impact on patients' lives by identifying and educating about anxiety disorders, directing patients to appropriate self-help resources, choosing evidence-based drug treatment when indicated, and making referrals for specialist care. PMID- 17868757 TI - Navigating the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study: practical outcomes and implications for depression treatment in primary care. AB - The Sequenced Treatment Alternatives to Relieve Depression (STAR( *)D) study addressed many clinically relevant issues on treatment of depressed outpatients. The study used an equipoise-stratified randomization scheme that enhanced the real-world expediency of treatment options studied. Because patients who had significant comorbid medical and psychiatric problems were included, and care was provided in the outpatient primary care setting as well as in outpatient psychiatric centers, findings are relevant to primary care physicians. The use of measurement-based treatment protocols promotes objectivity in a realm of often subjective clinical decision making. Although STAR( *)D was unable to provide specific treatment comparisons for patients at all study levels, it succeeded in defining the prevalence of treatment-resistant depression and is a model for further practical clinical outcomes studies. PMID- 17868758 TI - Bipolar spectrum disorder: differential diagnosis and treatment. AB - Bipolar disorder commonly presents as a recurrent mood disorder characterized by frequent depressive episodes. Although manic or hypomanic phases are required for the diagnosis to be made based on current diagnostic criteria, a wider expression of mood instability and other historical features or family history may suggest the presence of a bipolar spectrum illness. This article covers the diagnostic issues related to bipolar disorder and the spectrum concept of the illness. A new definition of bipolar spectrum disorder is suggested, and treatment principles and options are discussed. Primary care providers often encounter patients who have depression and mood problems, placing them in a key position for the diagnosis and treatment of this psychiatric illness. PMID- 17868759 TI - Efficient counseling techniques for the primary care physician. AB - Up to 60% of ambulatory primary care patients have psychosocial factors contributing to their symptom presentation. Counseling, although helpful, is seen as requiring specialized training that most primary care physicians lack, as well as being complex and time-consuming. Several counseling methods have been developed that are brief, relatively easy for the physician to learn and implement, and patient-centered. These include the BATHE technique, the FRAMES strategy, the Stages of Change (Transtheoretical Model) approach, and Motivational Interviewing. Although limited, available research suggests that carefully targeted brief counseling in medical settings does produce meaningful change. PMID- 17868760 TI - Integrating mental health and primary care. AB - Mental health and primary care delivery systems have evolved to operate differently. For example, attention to multiple medical issues, health maintenance, and structured diagnostic procedures are standard elements of primary care rarely incorporated into mental health care. A multidisciplinary treatment approach, group care, and case management are common features of mental health treatment settings only rarely used in primary care practices. Advances in treatments for mental health disorders and increased knowledge of the integral link between mental health and physical health encourage mental health disorder treatment in primary care settings, which reach the most patients. Effective integration of mental health care into primary care requires systematic and pragmatic change that builds on the strengths of both mental health and primary care. PMID- 17868761 TI - Adult post-traumatic stress disorder: screening and treating in primary care. AB - Trauma and post-traumatic stress disorder (PTSD) affect patients' physical health and daily functioning. Primary care physicians should remember to screen for trauma history and symptoms of PTSD when patients present with somatization, chronic pain, or other unexplained symptoms. Perceived loss of control, including physical examinations and procedures, may be frightening, and physicians should ask the patient's permission before touching them. Patients who have PTSD benefit from treatment, including both psychopharmacology (primarily selective serotonin reuptake inhibitors) and psychotherapy. Finally, hearing patients' stories of trauma and exposure to very sick patients can be traumatizing for physicians, who are encouraged to actively engage in self-care activities. PMID- 17868762 TI - Practical behavior change counseling in primary care. AB - Unhealthy behaviors lead to significant preventable morbidity and mortality in the United States. Primary care providers are in a unique position to address these issues with patients. Despite the importance and opportunity for health behavior counseling in primary care, reported rates are low. This article presents a practical model for health behavior counseling in everyday clinical practice. PMID- 17868763 TI - Personality disorders. AB - Personality disorders are gaining a similar level of attention in the primary care literature as afforded to mood, anxiety, and substance abuse disorders. A personality disorder-comorbid with a medical or other psychiatric diagnosis presents a challenge for primary care physicians because of diagnostic and treatment dilemmas, as well as management of the physician's interpersonal reaction to the patient. This article reviews research on prevalence, clinical presentation and assessment, and treatment, with specific recommendations for primary care physicians. Strategies to enhance the physician-patient relationship, including the use of empathic skills and the facilitation of physician well-being, are presented. Integrating these tools into routine practice can lead to more satisfying treatment relationships between primary care physicians and patients who have personality disorders. PMID- 17868764 TI - Screening and responding to family and intimate partner violence in the primary care setting. AB - It is now widely recognized that family violence and intimate partner violence (IPV) is prevalent, affecting 1 to 4 million women a year in the United States alone. Children and men are also victims of IPV. The consequences can be devastating and can affect both mental and physical health. The aims of this article are to review prevalence data, review mental and physical health consequences, and discuss screening and interventions appropriate to primary health care settings. PMID- 17868765 TI - Insomnia: an ignored health problem. AB - Insomnia is common in all age groups and impairs quality of life. Untreated insomnia can lead to, or cause worsening of, other health problems. Effective treatment is available. Behavioral approaches should be tried first with chronic insomnia, because they are effective with few adverse effects. A number of medicines are effective for insomnia, but providers need to be cautious with their use because they are expensive, have a number of adverse side effects, and their long-term use has not been studied. PMID- 17868766 TI - Geometric determinants of shape segmentation: tests using segment identification. AB - The geometric determinants of shape decomposition were studied using a performance-based method. Observers' identification of contour segments was shown to be systematically modulated by their curvature properties, and by the geometric properties of the enclosed region. Specifically, negative minima of contour curvature provided the best segment boundaries. Segments with negative minima boundaries were identified with greater accuracy than those with positive maxima or inflection boundaries of comparable length. Additionally, segment identification was shown to be determined by contour length, the turning angle at part boundaries, and the width at the part's base (hence the part's protrusion). The results indicate that part decomposition is an automatic process. Moreover, this process is graded, i.e. parts are more strongly segmented, or more likely to be perceived, according to the strength of many geometric determinants. PMID- 17868767 TI - Stimulus dependence of the flash-lag effect. AB - When two moving objects are presented in perfect alignment, but are not visible for the same amount of time, the briefer object will often be perceived as "lagging" the object of greater duration. Most investigations of this flash-lag effect (FLE) employ high velocity broadband stimuli, such as lines or dots with sharp boundaries and flashes with rapid onset and offset. We introduce a stimulus paradigm with narrow-band stimuli and measure the stimulus dependence of the FLE when basic stimulus parameters of spatio-temporal frequency and temporal duration are varied. We suggest that this dependence is consistent with the involvement of early visual mechanisms and interpret our results in the context of existing theories of the FLE. PMID- 17868768 TI - PLP catabolism: identification of the 4-pyridoxic acid dehydrogenase gene in Mesorhizobium loti MAFF303099. AB - The function of the mlr6793 gene from Mesorhizobium loti MAFF303099 has been identified. This gene encodes 4-pyridoxic acid dehydrogenase, an enzyme involved in the catabolism of PLP (Vitamin B6). This enzyme was overexpressed in Escherichia coli and characterized. 4-Pyridoxic acid dehydrogenase is a 33kDa protein that catalyzes the four electron oxidation of 4-pyridoxic acid to 3 hydroxy-2-methylpyridine-4,5-dicarboxylate, using nicotinamide adenine dinucleotide as a cofactor. The k cat for NADH production is 0.01s(-1). The KM values for 4-pyridoxic acid and NAD are 5.8 and 6.6microM, respectively. PMID- 17868769 TI - Complexation-flocculation of organic contaminants by the application of oxyhumolite-based humic organic matter. AB - Control of hazardous organic micropollutants is a challenging water quality issue. Dissolved humic organic matter (DOM) isolated from oxyhumolite coal mined in Bohemia was investigated as a complexation agent to remove polycyclic aromatic hydrocarbons (PAHs) and functionalized phenols from water by a two-stage process involving complexation and flocculation. After the formation of humic-contaminant complexes, ferric salts were added resulting in the precipitation and flocculation of the DOM and the associated pollutants. Flocculation experiments with ferric ion coagulants indicated that precipitation of oxyhumolite DOM together with the complexed contaminants occurred at lower ferric ion concentrations than with the reference DOM in acidic environments (pH approximately 3.5). The complexation-flocculation removal rates for non-reactive PAHs characterized by small localization energies of pi-electrons correlated well with the complexation constants. On the other hand, the combined complexation flocculation removal rates for activated PAHs including trans-stilbene, anthracene and 9-methyl anthracene, as well as functionalized polar phenols, were higher than predicted from the complexation coefficients. Methodological studies revealed for the first time that the ferric ion coagulant contributed to enhanced removal rates, most probably due to ferric ion-catalyzed pollutant degradation resulting in oxidized products. PMID- 17868770 TI - Biotransformation and antioxidant enzymes of Lumbriculus variegates as biomarkers of contaminated sediment exposure. AB - In this study the black worm Lumbriculus variegatus was tested for suitability as biomonitor for moderately contaminated sediments. The response capacity of the biotransformation system phase II enzyme glutathione-S-transferase (GST) and the oxidative defense enzyme catalase (CAT) to contaminated sediment and atrazine was investigated to establish them as sensitive biomarkers. To get an integrated view on the enzyme activity kinetics, increasing concentrations of the herbicide atrazine were applied to stimulate GST response, and relationship between enzyme activity and herbicide concentration was observed at various exposure durations. Furthermore, animals were exposed for up to 1 week to sediments of four typical urban river sections with high anthropogenic impact. L. variegatus was capable to accomplish the environmental stress and the selected enzymes showed elevation. Significant changes of GST (membrane-bound and soluble) were detected after at least 4 days of exposure to atrazine and contaminated sediments. Although CAT increase could be observed already after 1 day of exposure to sediments, an exposure time of one week is considerable for accurate interpretation of the enzymatic response. The clear enzymatic response of especially the membrane-bound GST indicated charges with organic lipophilic substances at all sampling sites. PMID- 17868771 TI - Phosphorus fractionation in volcanic lake sediments (Azores - Portugal). AB - The phosphorus distribution in volcanic sediments of three lakes that are under different anthropogenic pressures in Sao Miguel island (Azores - Portugal) was evaluated using a sequential extraction scheme. The P-fractionation scheme employs sequential extractions of sediment with NH4Cl, bicarbonate-dithionite (BD), NaOH (at room temperature), HCl and NaOH (at 85 degrees C) to obtain five P fractions. The P-fractionation shows that in lakes with higher trophic status (Lake Furnas and Lake Sete Cidades), the NaOH extracted P is the dominant fraction, that contribute with more than 50% to total sedimentary phosphorus. The rank order of P-fractionation for these two lakes was NaOH>NaOH (85 degrees C)>HCl>BD>NH4Cl for Furnas lake and NaOH>HCl>NaOH (85 degrees C)>NH4Cl>BD for Sete Cidades lake. On the other hand, the trend of P contribution in the oligotrophic lake Fogo shows that the most inert P pools have the higher concentrations, with more than 50% of the P contribution from the last extraction step with NaOH at 85 degrees C. For this lake, the rank order of P-fractionation was NH4Cl>BD>NaOH>HCl>NaOH (85 degrees C). The Phosphorus Maximum Solubilization Potential (P-MSP) was also calculated and the results show that for the more bio available P-fractions (first and second extraction step), the P-MSP values for Furnas and Sete Cidades lakes are sensibly higher than the results obtained in Fogo lake, an indication of the non-point diffuse load discharged in the first ones. PMID- 17868772 TI - Effects of pollutants on laccase activities of Marasmius quercophilus, a white rot fungus isolated from a Mediterranean schlerophyllous litter. AB - Marasmius quercophilus is a white-rot fungus involved in carbon recycling in Mediterranean ecosystems because of its laccase production. Here we described the effect of metal ions and halide salts, on laccase activity in order to point out the action of such environmental pollutants on this enzyme of major importance. Furthermore we tested organic solvent effects on laccase reaction since reaction mixture including solvent can be used in the transformation of xenobiotics. In the case of metal ions, we found that chloride ions were responsible for inhibition while CuSO(4) and MnSO(4) enhanced laccase activity. When halides were tested, we showed the following degree of inhibition: F(-)>Cl(-)>Br(-). Furthermore we found that I(-) was oxidized by laccase with I(2) as the product of the reaction. With ABTS, 50% of the laccase activity remains for solvent concentration ranging from 40% to 60% depending on the solvent used while with syringaldazine solvent concentration ranged from 50% to 70%. The organic solvent effects observed were probably a result of enzyme denaturation and of both enhancement of oxidised product solubilisation and of substrate solubilisation (for syringaldazine). These results show that laccase from M. quercophilus is not rapidly inhibited by certain environmental pollutants which sustains its role in carbon turnover under pertubation. However the strong effect of chloride ion on laccase activity should be further investigated with in situ studies since this could drastically influence carbon recycling in litters from Mediterranean littoral locations. PMID- 17868774 TI - Clinical significance of prostaglandin E synthase expression in gastric cancer tissue. AB - Studies have linked microsomal prostaglandin E synthase (mPGES)-1 with gastric cancer. The purpose of this study was to determine mPGES-1, mPGES-2, and cytosolic PGES (cPGES) expression in gastric cancer and to evaluate the correlation between mPGES-1 and mPGES-2 expression and clinicopathological factors and cyclooxygenase-2 expression. PGES protein expression was examined by Western blot in gastric cancer cell lines and in biopsy samples from patients with gastric cancer. mPGES-1, mPGES-2, and cPGES protein localizations were examined immunohistochemically in 129 archival gastric cancer surgical resections. mPGES-1 protein expression was found in gastric cancer biopsies and cancer cell lines with differentiated or undifferentiated adenocarcinoma. There was no mPGES-1 expression in nonneoplastic biopsies. All cell lines and tissue samples expressed mPGES-2 and cPGES. Immunohistochemical analysis showed cancer cells expressed mPGES-1 in 47% of cases. mPGES-2 immunoreactivity was seen both in nonneoplastic glandular epithelium and cancer cells; however, cancer cell immunoreactivity was significantly more pronounced in 29% of cases. cPGES expression was constitutive both in nonneoplastic and neoplastic tissues, with no significant variation among cases. mPGES-1 and mPGES-2 expression correlated with cyclooxygenase-2 expression. mPGES-1 and mPGES-2 expression, and tumor-node metastasis stage had independent prognostic significance under multivariate analysis in patients with gastric cancer overall and in patients with differentiated cancers. However, only tumor-node-metastasis stage and mPGES-2 expression retained independent prognostic significance in patients with poorly differentiated cancers. mPGES-1 and mPGES-2 correlate with clinicopathological factors and may be valuable prognostic factors in gastric cancer. PMID- 17868773 TI - Stromogenic prostatic carcinoma pattern (carcinomas with reactive stromal grade 3) in needle biopsies predicts biochemical recurrence-free survival in patients after radical prostatectomy. AB - We previously reported that reactive stromal grading in radical prostatectomies is a predictor of recurrence and that reactive stromal grading 0 and 3 are associated with lower biochemical recurrence-free survival rates than reactive stromal grading 1 and 2. We explored the prognostic significance of reactive stromal grading in preoperative needle biopsies. At Baylor College of Medicine, 224 cases of prostatic carcinoma were diagnosed by needle biopsy. Reactive stromal grading was evaluated on hematoxylin-eosin (H&E)-stained sections on the basis of previously described criteria: grade 0, with 0% to 5% reactive stroma; grade 1, 6% to 15%; grade 2, 16% to 50%; grade 3, 51% to 100%, or at least a 1:1 ratio between glands and stroma. Kaplan-Meier and Cox proportional hazard analyses were used. Reactive stromal grading distribution was as follows: reactive stromal grading 0, 1 case (0.5%); reactive stromal grading 1, 149 cases (66.5%); reactive stromal grading 2, 59 cases (26.3%); reactive stromal grading 3, 15 cases (6.7%). Reactive stromal grading in biopsies was correlated with adverse clinicopathologic parameters in the prostatectomy. Patients with reactive stromal grading 1 and 2 had better survival than those with 0 and 3 (P = .0034). Reactive stromal grading was an independent predictor of recurrence (hazard ratio = 1.953; P = .0174). Reactive stromal grading is independent of Gleason 4 + 3 and 3 + 4 in patients with a Gleason score of 7. Quantitation of reactive stroma and recognition of the stromogenic carcinoma in H&E-stained biopsies is useful to predict biochemical recurrence in prostate carcinoma patients independent of Gleason grade and prostate-specific antigen. PMID- 17868775 TI - Colorectal adenocarcinoma involving the prostate: report of 9 cases. AB - We present 9 consult cases, the largest series to date, of colorectal adenocarcinoma involving the prostate. Mean age of patients at diagnosis was 61 years (range, 42-78 years). Six cases were initially diagnosed on needle biopsy and the others by transurethral resection. Three cases were diagnosed before biopsy of the colon, which led to the discovery of a primary colonic tumor. The mean interval between the detection of the primary colonic tumor and prostatic involvement in the other 6 cases was 30 months (range, 1-52 months). At diagnosis, the stages of colorectal carcinomas were pT1 (n=2), pT2 (n=2), pT3 (n=2), and pT4 (n=3). Two cases involved the prostate after the recurrence of rectal adenocarcinoma at the anastomotic site of the previous colonic resection. In most cases, the tumors were typical moderately differentiated with occasional poorly differentiated foci. Other histologic features included desmoplastic stromal reaction (100%, n=9), necrosis (77.8%, n=7), chronic inflammatory response (77.8%, n=7), cribriform pattern (66.7%, n=6), villous architecture (22.2%, n=2), mucin production (22.2%, n=2), signet-ring cells (11.1%, n=1), and perineural invasion (11.1%, n=1). Immunohistochemical stains were positive for beta-catenin in 6 of 6 cases, CDX2 in 6 of 6 cases, carcinoembryonic antigen in 7 of 7 cases, CK20 in 5 of 6 cases, high-molecular-weight cytokeratin in 5 of 6 cases, and alpha-methylacyl-CoA racemase in 3 of 6 cases. Stains were negative in all cases for prostate-specific antigen, P501S (prostein), and CK7. Six patients (66.7%) died of disease within an average of 34 months (range, 8-88 months) after diagnosis of prostatic involvement. There are critical therapeutic and prognostic implications for distinguishing between prostatic adenocarcinoma and colorectal carcinoma involving the prostate. Colorectal adenocarcinoma should be considered on prostate sampling when carcinoma exhibits either "dirty" necrosis, tall columnar epithelium with mucin production, mucin-positive signet-ring cells, villous architecture, or associated inflammation. Immunohistochemical stains for beta-catenin, CDX2, carcinoembryonic antigen, high-molecular-weight cytokeratin, prostate-specific antigen, P501S (prostein), CK20, and CK7 can be helpful in making a definitive diagnosis. PMID- 17868776 TI - A feasibility study of virtual slides in surgical pathology in China. AB - China's huge territorial expanse and its imbalance of regional economic development have resulted in an uneven distribution of experienced pathologists. Developing telepathology for consultation is of special relevance to China. We developed a newly designed telepathology workstation, which includes a small file size of each slide, permitting easy transmission, storage, and manipulation, and a feedback function, and also evaluated its feasibility in surgical pathology in China. Four hundred cases covering a broad spectrum of surgical pathology problems were investigated in a blinded fashion by the 2 pathologists using this virtual microscope system. These cases were then randomized and re-reviewed a second time with light microscope. Diagnoses and time spent for each diagnosis were recorded for both methods. The diagnostic accuracies achieved by viewing glass slides and virtual images were 97.25% (389 of 400) and 95.5% (382 of 400) for pathologist A and 96.25% (385 of 400) and 94.75% (379 of 400) for pathologist B, respectively. There was no significant diagnostic discrepancy between the 2 methods for the 2 pathologists. The average times for viewing a virtual slide were 3.41 and 5.24 minutes for pathologists A and B, respectively, whereas the average times for viewing a glass slide were 1.16 and 3.35 minutes for pathologists A and B. There was a statistical difference between the time costs of the 2 methods. However, the slight time increase using virtual slides is less than that using dynamic telepathology and traditional consultation, and is acceptable to the pathologists. These results showed that this newly designed virtual microscope system have an acceptable diagnostic accuracy that is of practical value and may be suitable for application in China. PMID- 17868777 TI - MRI-directed, wire-localized breast excisions: incidence of malignancy and recommendations for pathologic evaluation. AB - Magnetic resonance imaging (MRI) has an evolving role in the evaluation of breast lesions and is currently being used for the screening of high-risk patients (eg, women with a personal or family history of breast cancer), for the evaluation of extent of disease in patients with a current diagnosis of cancer, and for patients with suspicious, but indeterminate, findings by other imaging modalities. If a suspicious lesion detected by MRI is not well visualized by another method, an MRI-directed core biopsy or breast excision may be performed. MRI cannot be used to verify the lesion in the specimen because MRI lesion detection is dependent on uptake of gadolinium after intravenous injection. Accordingly, these breast excisions present unique challenges to pathologists. The purpose of this report is to define the surgical pathology issues involved in processing MRI-localized excisions. Retrospective review of 85 consecutive MRI directed breast excisions from 77 patients was performed. Malignant lesions were present in 20 (24%) of 85 excisions, including 10 cases of invasive carcinoma (median size, 0.4 cm), 9 cases of ductal carcinoma in situ, and 1 case of lymphoma. Most of the malignancies (85% or 17/20) had no associated gross finding and only 5 (25%) of 20 of these malignancies were associated with a definite finding on the specimen radiograph. This study demonstrates that gross examination and specimen radiography do not identify most of the malignancies in MRI-localized biopsies and, therefore, optimal processing requires complete microscopic examination of these specimens. PMID- 17868778 TI - Theropithecus and 'Out of Africa' dispersal in the Plio-Pleistocene. AB - Theropithecus oswaldi was one of the most widely distributed Plio-Pleistocene primates, found in southern, East, and North Africa, as well as in Spain, India, and possibly Italy. Such a large geographic range for a single primate species is highly unusual. Here, the nature and timing of its dispersal is examined using the Stepping Out cellular automata model. A hypothetical dispersal of T. darti is also modelled to assess whether the late Pliocene might have been a more favorable period for Afro-Eurasian dispersal than the early Pleistocene. Stepping Out draws on climatic and biome reconstruction to provide the paleovegetative and climatic background necessary for the simulations, and model parameters for T. oswaldi and T. darti were set a priori on the basis of their fossil records and paleobiologies. The simulations indicate that T. darti could have readily left Africa in the Pliocene, and that it swiftly reaches Asia. A European T. darti colonization was less certain and less rapid. The simulated T. oswaldi dispersal out of Africa was slower, but nonetheless T. oswaldi arrived at Mirzapur within the time period indicated by the fossil record. Using the a priori parameters, T. oswaldi did not arrive at the European sites of Cueva Victoria and Pirro Nord. It cannot be discounted, therefore, that some of the European fossils are a result of an earlier T. darti dispersal. The simulations also showed that in order for Theropithecus to reach Europe, it needed to be tolerant of a relatively wide range of habitats. In addition, our finding that Asian colonization was more rapid and more probable parallels the information from the hominin fossil record, in which the fossils from Asia predate those from Europe by several hundred thousand years. PMID- 17868779 TI - New hominid remains associated with Gravettian parietal art (Les Garennes, Vilhonneur, France). PMID- 17868780 TI - Systematic butchering of fallow deer (Dama) at the early middle Pleistocene Acheulian site of Gesher Benot Ya'aqov (Israel). AB - Three assemblages of fallow deer (Dama sp.) bones excavated from the early middle Pleistocene (oxygen isotope stage 18) layers of the Acheulian site of Gesher Benot Ya'aqov, Israel, furnish evidence of systematic and repeated exploitation of complete carcasses by hominins. The excellent state of preservation of the bones and the presence of only minimal signs of carnivore involvement permit an investigation of the role of hominins as the primary agents responsible for the damage to these bones. Hominin expertise in dealing with fallow deer carcasses is manifested by cut marks, percussion marks, and hack marks on the bones. The archaeozoological analysis of the anatomical position and frequency of these marks suggests that carcass processing followed systematic practices that reflect an in-depth knowledge of fallow deer anatomy and a consistent behavioral strategy. These assemblages represent one of the earliest examples of methodological butchering practices in Eurasia. The evidence of carcass processing observed at Gesher Benot Ya'aqov resembles that seen in late Pleistocene sites in Israel, which were inhabited by modern humans. We interpret the Gesher Benot Ya'aqov data as indicating that the Acheulian hunters at the site (1) were proficient communicators and learners and (2) possessed anatomical knowledge, considerable manual skill, impressive technological abilities, and foresight. PMID- 17868781 TI - Dissolved organic matter fluorescence as a water-flow tracer in the tropical wetland of Pantanal of Nhecolandia, Brazil. AB - The Nhecolandia is a sub-region of the Brazilian Pantanal wetland, where saline and freshwater lakes coexist in close proximity. Measurements of dissolved organic carbon (DOC) content and analysis of fluorescence excitation-emission matrices (EEM) were conducted in an effort to characterize spatial variability in concentration and source of dissolved organic matter (DOM) and to further understand the hydrochemical functioning of this complex environment. Increasing pH under the influence of evaporation resulted in an increasing DOC solubility ranging from 50 to over 300 mgC L(-1) in surface water. Spectrofluorescence characterisation indicates the presence of several families of dissolved organic matter (fulvic and humic-type and proteinaceous materials), which are related to the type of lake and its hydro-bio-geochemical functioning. Moreover, the fluorescence signatures from lake water DOM and from surrounding soil-water extracted organic matter (WEOM) show strong similarities although some labile proteinaceous compounds disappeared during humification. Results from the characterisation of DOM and WEOM not only suggest that spectrofluorescence is a reliable technique for the tracing of water flows, but also for the marking of the origin of organic horizons in this environment. PMID- 17868782 TI - Modelling the cardiac transverse-axial tubular system. AB - The transverse-axial tubular system (TATS) of cardiac ventricular myocytes is a complex network of tubules that arises as invaginations of the surface membrane; it appears to form a specialised region of cell membrane that is particularly important for excitation-contraction coupling. However, much remains unknown about the structure and role of the TATS. In this brief review we use experimental data and computer modelling to address the following key questions: (i) What fraction of the cell membrane is within the TATS? (ii) Is the composition of the TATS membrane the same as the surface membrane? (iii) How good is electrical coupling between the surface and TATS membranes? (iv) What fraction of each current is within the TATS? (v) How important is the complex structure of the TATS network? (vi) What is the effect of current inhomogeneity on lumenal ion concentrations? (vii) Does the TATS contribute to the functional changes observed in heart failure? Although there are many areas in which experimental evidence is lacking, computer models provide a method to assess and predict the possible function of the TATS; such models suggest that although the surface and TATS membranes are electrically well coupled, concentration of ion flux pathways within the TATS, coupled to restricted diffusion, may result in the ionic composition in the TATS lumen being different from that in the bulk extracellular space, and varying with activity and in pathological conditions. PMID- 17868784 TI - Multi-scale system biology applied to cervical inter-epithelial neoplasia. PMID- 17868785 TI - Could follow-up different modalities play a role in asymptomatic cervical cancer relapses diagnosis? An Italian multicenter retrospective analysis. AB - OBJECTIVE: The aim of this study was to evaluate how much clinical surveillance performed by follow-up scheduled appointments may correctly identify asymptomatic recurrences and describe the pattern of relapse detected by procedures. METHODS: The records of 327 consecutive women with recurrent cervical cancer treated from 1980 to 2005 were retrospectively collected in 8 Italian Institutions. Primary disease and recurrence data were picked up: diagnosis, type of treatment, FIGO stage, tumour grade, histology, clinical lesion size, number of localizations and site of relapse, presence of symptoms and primary method of detection, the type of treatment of recurrence and follow-up data, such as appointment date, clinical status and procedure performed. A multivariate analysis was carried out using the Cox proportional hazards regression model. Survival curves were calculated using the Kaplan-Meier technique. Survival differences were evaluated by the log-rank test. RESULTS: Sixty-seven out of 327 patients (20.5%) had a local recurrence on vaginal vault, 120 (36.7%) in central pelvis, 31 (9.5%) in pelvic wall, 16 cases (4.9%) in lymph nodes. Seventy-nine patients (24.2%) showed a distant relapse while 14 (4.3%) developed both a distant and local relapse. Among patients with distant relapses 39 (49.4%) had lung metastasis, 41 (51.9%) an hepatic recurrence, 4 (5.1%) a bone relapse. Among distant sites 32 out of 79 patients (40.5%) had single relapse and 46 (58.2%) had multiple localizations. The site of relapse influenced survival since patients with vaginal vault recurrences lived significantly longer than patients with recurrences in other sites. Ninety-seven (29.7%) patients were symptomatic and anticipated the scheduled visit, 66 (20.2%) reported their symptoms during the follow-up visit and 164 (50.1%) were asymptomatic and the diagnostic path was introduced by a planned visit or exam. Between asymptomatic patients the first procedure was clinical visit for 85 patients out of 164 patients (51.8%), imaging for 60 patients (36.6%), both clinical visit and imaging for 14 (8.5%) and cytology for 5 (3%, Pap smear test). The median OS of symptomatic patients was 37 months versus 109 months of asymptomatic patients (Log rank, p=0.00001). The median survival since recurrence was 9 months for symptomatic patients and median was not reached for asymptomatic patients (p<0.0001). The median disease-free interval was 24 months for asymptomatic patients vs. 36 months for symptomatic patients (p=0.03). CONCLUSIONS: Our study helps demonstrate the great need of prospective cost effectiveness studies which are lacking at the present time. PMID- 17868786 TI - Hypertension and the kidney: new avenues for an improved management of hypertension in renal diseases: introduction. PMID- 17868787 TI - Renin inhibition: what are the clinical perspectives? AB - Evidence that renin system blockade is useful in many patients with hypertension is overwhelming. Two recent lines of investigation have suggested that more complete blockade leads to improved clinical outcomes. One line of investigation involves the use of a combination of an angiotensin-converting enzyme inhibitor with an angiotensin-receptor blocker. The second line of investigation involves the use of very high dose angiotensin-receptor blocker. The interaction of renin with substrate is the rate-limiting step in the renin cascade; thus, the recent development of a powerful renin inhibitor also favors more complete blockade of the system. In many patients, this is likely to lead to improved treatment. PMID- 17868788 TI - The (pro)renin receptor: a new kid in town. AB - Renin inhibitors are now available in therapeutic doses and it is accepted that they decrease blood pressure as efficiently as the classic inhibitors of the renin-angiotensin system (RAS): angiotensin converting enzyme inhibitors and angiotensin II-receptor blockers (ARBs). One major issue will be to know how, beyond the normalization of blood pressure, renin inhibitors (RIs) will compare with angiotensin converting enzyme inhibitors and ARBs for their ability to protect the organs against the tissue damage associated with overactivation of the RAS. The mechanism(s) of tissue protection may involve the inhibition of a direct cellular effect of renin and prorenin mediated by the (pro)renin receptor ([P]RR). This review updates the recent findings on (P)RR; its role in hypertension, cardiac fibrosis, diabetic nephropathy, and retinopathy; and the effects of a putative (P)RR antagonist. PMID- 17868789 TI - The (pro)renin receptor and the kidney. AB - Prorenin binding to the (pro)renin receptor not only causes a nonproteolytic activation of prorenin leading to the activation of the renin-angiotensin system (RAS), but also stimulates the receptor's own intracellular signaling pathways independent of the RAS. Within the kidneys, the (pro)renin receptor is present in the glomerular mesangium and podocytes, which play an important role in the maintenance of the glomerular filtration barrier. Therefore, prorenin-receptor blockers, which competitively bind to the receptor as a decoy peptide, have superior benefits with regard to proteinuria and glomerulosclerosis in experimental animal models with elevated plasma prorenin levels such as diabetes and hypertension compared with conventional RAS inhibitors, possibly by inhibiting both the nonproteolytic activation of prorenin and RAS-independent intracellular signals. PMID- 17868790 TI - The association of aldosterone with obesity-related hypertension and the metabolic syndrome. AB - Overweight and obesity are associated with arterial hypertension. Given the large increase in the obesity prevalence worldwide, the number of obese patients with hypertension is likely to increase substantially in the near future. Overweight and obese patients are exposed to an important metabolic and cardiovascular risk. The understanding of the mechanisms linking obesity to hypertension is important for specific prevention and therapy in this population. There is some evidence that obesity is associated with an increased aldosterone level. To date, 2 mechanisms may explain the interaction of fat tissue with the renin-angiotensin aldosterone system, and therefore explain, in part, obesity-related hypertension. First, human adipose tissue produces several components of the renin-angiotensin aldosterone system, mainly adipose tissue-derived angiotensinogen. Second, increased fatty acid production in the obese patient, especially nonesterified fatty acids, might stimulate aldosterone production, independent of renin. A better understanding of these mechanisms might have implications for the management of hypertension in overweight and obese patients. Because aldosterone also is associated with blood glucose and blood lipids, selective aldosterone blockade may represent a particularly attractive therapeutic strategy in obese patients with a clustering of cardiovascular risk factors. PMID- 17868791 TI - Ambulatory blood pressure and cardiovascular events in chronic kidney disease. AB - Hypertension is an important risk factor for adverse cardiovascular and renal outcomes, particularly in patients with chronic kidney disease (CKD). This review compares blood pressure (BP) measurements obtained in the clinic with those obtained outside the clinic to predict cardiovascular and renal injury and outcomes. Data are accumulating that suggest that ambulatory BP monitoring is a superior prognostic marker compared with BP values obtained in the clinic. The use of ambulatory BP monitoring can detect white-coat hypertension and masked hypertension, which results in less misclassification of BPs. Ambulatory BP monitoring is a marker of cardiovascular end points in CKD. Nondipping is associated with proteinuria and lower glomerular filtration rate. Although nondipping is associated with more end-stage renal disease and cardiovascular events, adjustment for other risk factors removes the prognostic significance of nondipping. For patients with CKD who are not on dialysis, 24-hour ambulatory BPs of less than 125/75 mm Hg, daytime ambulatory BP of less than 130/85 mm Hg, and nighttime ambulatory BPs of less than 110/70 mm Hg appear to be reasonable goal BP targets. In the management of hypertension in patients with CKD, control of hypertension is important. Ambulatory BP monitoring may be useful to assign more aggressive treatment to patients with masked hypertension and withdraw antihypertensive therapy in patients with white-coat hypertension. Ambulatory BP monitoring can refine cardiovascular and renal risk assessment in all stages of CKD. The independent prognostic role of nondipping is unclear. PMID- 17868792 TI - Rationale for combining blockers of the renin-angiotensin system. AB - Blockade of the renin-angiotensin system (RAS) with angiotensin I-converting enzyme (ACE) inhibitors and AT1-receptor (AT1R) blockers has become one of the most successful therapeutic approaches in medicine. The question is no longer whether RAS inhibition helps, but rather how we can optimize inhibition to achieve optimal cardiovascular and renal protection. Indeed, numerous data have shown that the RAS is not blocked fully over 24 hours with current doses of RAS blockers because they trigger a counter-regulatory renin release that can offset pharmacologic inhibition of the RAS. This absence of full blockade may have clinical implications. Combination therapy with ACE inhibitors and AT1R antagonists thus has been proposed to inhibit the biological effects of the reactive renin release triggered by single-site RAS inhibition. By using this approach, numerous experimental and clinical studies have suggested that this combination therapy has additive or synergistic effects on blood pressure and on the prevention of cardiovascular and renal lesions. Although similar intensity of RAS blockade can be achieved by either combination therapy or by using high doses of an AT1-receptor antagonist given alone, the ACE inhibitor present in the combination interferes with the bradykinin-nitric oxide pathway and the N-acetyl Ser-Asp-Lys-Pro metabolism, which both may have additional biological effects. PMID- 17868793 TI - Should beta-blockers be used to control hypertension in people with chronic kidney disease? AB - Activation of the sympathetic nervous system is common in patients with chronic kidney disease, plays an important role in the genesis of hypertension, the rate of decrease of renal function, and is associated with the increased cardiovascular morbidity and mortality seen in these patients. beta-blockers are potent antihypertensive agents but differ in their hemodynamic effects on renal function. The cardioselective beta-blockers such as atenolol and metoprolol are known to retard the progression of renal diseases, but to a lesser degree compared with blockers of the renin-angiotensin-aldosterone system. However, the newer vasodilating beta-blockers such as carvedilol and nebivolol have different effects on renal hemodynamics and function primarily because of its greater adjunctive alpha1-blocking activity. Carvedilol decreases renal vascular resistance and prevents reductions in the glomerular filtration rate and renal blood flow in patients with hypertension with or without impaired kidney function. In addition, carvedilol may retard progression of albuminuria, and provide cardiorenal protection in chronic kidney disease patients with hypertension, congestive heart failure, and at high risk for sudden cardiac death. PMID- 17868794 TI - Renal sodium handling and nighttime blood pressure. AB - Blood pressure follows a circadian rhythm with a physiologic 10% to 20% decrease during the night. There is now increasing evidence that a blunted decrease or an increase in nighttime blood pressure is associated with a greater prevalence of target organ damage and a faster disease progression in patients with chronic kidney diseases. Several factors contribute to the changes in nighttime blood pressure including changes in hormonal profiles such as variations in the activity of the renin-angiotensin and the sympathetic nervous systems. Recently, it was hypothesized that the absence of a blood pressure decrease during the nighttime (nondipping) is in fact a pressure-natriuresis mechanism enabling subjects with an impaired capacity to excrete sodium to remain in sodium balance. In this article, we review the clinical and epidemiologic data that tend to support this hypothesis. Moreover, we show that most, if not all, clinical conditions associated with an impaired dipping profile are diseases associated either with a low glomerular filtration rate and/or an impaired ability to excrete sodium. These observations would suggest that renal function, and most importantly the ability to eliminate sodium during the day, is indeed a key determinant of the circadian rhythm of blood pressure. PMID- 17868795 TI - Effects of xenoestrogens on the differentiation of behaviorally-relevant neural circuits. AB - It has become increasingly clear that environmental chemicals have the capability of impacting endocrine function. Moreover, these endocrine disrupting chemicals (EDCs) have long term consequences on adult reproductive function, especially if exposure occurs during embryonic development thereby affecting sexual differentiation. Of the EDCs, most of the research has been conducted on the effects of estrogen active compounds. Although androgen active compounds are also present in the environment, much less information is available about their action. However, in the case of xenoestrogens, there is mounting evidence for long-term consequences of early exposure at a range of doses. In this review, we present data relative to two widely used animal models: the mouse and the Japanese quail. These two species long have been used to understand neural, neuroendocrine, and behavioral components of reproduction and are therefore optimal models to understand how these components are altered by precocious exposure to EDCs. In particular we discuss effects of bisphenol A and methoxychlor on the dopaminergic and noradrenergic systems in rodents and the impact of these alterations. In addition, the effects of embryonic exposure to diethylstilbestrol, genistein or ethylene,1,1-dichloro-2,2-bis(p-chlorophenyl) is reviewed relative to behavioral impairment and associated alterations in the sexually dimorphic parvocellular vasotocin system in quail. We point out how sexually dimorphic behaviors are particularly useful to verify adverse developmental consequences produced by chemicals with endocrine disrupting properties, by examining either reproductive or non-reproductive behaviors. PMID- 17868797 TI - B cell-derived exosomes can present allergen peptides and activate allergen specific T cells to proliferate and produce TH2-like cytokines. AB - BACKGROUND: Exosomes are vesicles of 30 to 100 nm produced by inward budding of endosomal compartments and are released by a range of different cell types. Exosomes from antigen-presenting cells carry immunorelevant molecules like MHC class I and II and costimulatory molecules and thus are suggested to have a role in immune modulation. OBJECTIVE: To investigate the role of antigen-presenting cell derived exosomes in allergen presentation and T-cell stimulation. METHODS: Exosomes were isolated from supernatants of B-cell lines derived from patients with birch pollen allergy. The exosomes were characterized with regard to the expression of surface molecules by flow cytometry. Moreover, exosomes were loaded with T-cell-activating peptides from the major birch allergen Bet v 1, and binding was tested with ELISA. Loaded exosomes were used for stimulation of Bet v 1-specific T-cell lines. Cell proliferation and cytokine production were assessed. RESULTS: The exosomes had a phenotype typical of B cell-derived exosomes with expression of MHC, costimulatory molecules like CD86, tetraspanin proteins such as CD81, and CD19. Furthermore, B cell-derived exosomes bound Bet v 1-derived peptides and subsequently induced a dose-dependent T-cell proliferation. In addition to proliferation, T cells synthesized the cytokines IL 5 and IL-13 in response to peptide-loaded exosomes. CONCLUSION: These results demonstrate for the first time that exosomes isolated from B cells can present allergen-derived peptides and thereby induce T-cell proliferation and T(H)2-like cytokine production. CLINICAL IMPLICATIONS: Our data suggest that exosomes from B lymphocytes are an immunostimulatory factor in allergic immune responses. PMID- 17868796 TI - Bupropion dose-dependently reverses nicotine withdrawal deficits in contextual fear conditioning. AB - Bupropion, a norepinephrine and dopamine reuptake inhibitor and nicotinic acetylcholine receptor antagonist, facilitates smoking cessation and reduces some symptoms of nicotine withdrawal. However, the effects of bupropion on nicotine withdrawal-associated deficits in learning remain unclear. The present study investigated whether bupropion has effects on contextual and cued fear conditioning following withdrawal from chronic nicotine or when administered alone. Bupropion was administered alone for a range of doses (2.5, 5, 10, 20 or 40 mg/kg), and dose-dependent impairments in contextual and cued fear conditioning were observed (20 or 40 mg/kg). Follow-up studies investigated if bupropion disrupted acquisition or expression of fear conditioning. Bupropion (40 mg/kg) administration on training day only produced deficits in contextual fear conditioning. Alternatively, bupropion (20 or 40 mg/kg) administration during testing dose-dependently produced deficits in contextual and cued fear conditioning. To test the effect of bupropion on nicotine withdrawal, mice were withdrawn from 12 days of chronic nicotine (6.3 mg/kg/day) or saline treatment. Withdrawal from chronic nicotine disrupted contextual fear conditioning; however, 5 mg/kg bupropion reversed this deficit. Overall, these results indicate that a low dose of bupropion can reverse nicotine withdrawal deficits in contextual fear conditioning, but that high doses of bupropion produce deficits in fear conditioning. PMID- 17868798 TI - Morphological and biochemical analysis of immature ovine oocytes vitrified with or without cumulus cells. AB - The cryopreservation of oocytes is an open problem as a result of their structural sensitivity to the freezing process. This study examined (i) the survival and meiotic competence of ovine oocytes vitrified at the GV stage with or without cumulus cells; (ii) the viability and functional status of cumulus cells after cryopreservation; (iii) the effect of cytochalasin B treatment before vitrification; (iv) chromatin and spindle organization; (v) the maturation promoting factor (MPF) and mitogen-activated protein kinase (MAPK) activity of vitrified oocytes after in vitro maturation. Sheep oocytes were vitrified at different times during in vitro maturation (0, 2, and 6 h) with (COCs) or without cumulus cells (DOs). After warming and in vitro maturation, oocytes denuded at 0 h culture showed a significantly higher survival and meiotic maturation rate compared to the other groups. Hoechst 33342/propidium iodide double staining of COCs and microinjection of Lucifer Yellow revealed extensive cumulus cell membrane damage and reduced oocyte-cumulus cell communications after vitrification. Cytochalasin B treatment of COCs before vitrification exerted a negative effect on oocyte survival. After in vitro maturation, the number of vitrified oocytes with abnormal spindle and chromatin configuration was significantly higher compared to control oocytes, independently of the presence or absence of cumulus cells. The removal of cumulus cells combined with vitrification significantly decreased the MPF and MAPK levels. This study provides evidence that the removal of cumulus cells before vitrification enhances oocyte survival and meiotic competence, while impairing the activity of important proteins that could affect the developmental competence of oocytes. PMID- 17868799 TI - Suicide ideation and social desirability among school-aged young people. AB - A mixed male-female sample of 950 school-aged adolescents, corresponding to 10% of the young population aged 15-19 living in a rural district of Northeast Italy, was investigated with self-reported questionnaires about the links between social desirability and suicide ideation. On the whole 30.6% of females and 23.9% of males reported suicidal ideation of some degree, with 5% in both genders reporting suicide ideation of a high degree (i.e. quite a lot/extremely often). Those who scored higher at the Marlowe-Crowne Social Desirability Scale (SDS) reported lower levels of psychiatric symptoms on the Symptom checklist 90R (SCL 90R), with the "denial" subscale of the SDS resulting specifically associated to lower scores on SCL-90R items measuring hopelessness, thoughts about death and suicide ideation. The personality traits measured by the Marlowe-Crowne SDS, such as defensiveness, denial and self-deception, might be conceived as a protection against psychiatric disorders and suicide ideation. PMID- 17868800 TI - Ethnic and national identity among second-generation immigrant adolescents in France: the role of social context and family. AB - This study, based on 365 second-generation adolescents from five ethnic groups, examined the cultural identity according to two orientations (ethnic and national) including two components (affirmation and exploration). Parents (356 mothers, 292 fathers) are also interviewed. Following ecological models of development and acculturation, multiple layers of context and their influence were analyzed: socialization with peers (ethnic composition of school and friends), the perception of discrimination and several aspects of parent adolescent relationship including the perception of adolescent of their relationship with parents and both mothers' and fathers' reports on their own ethnic and national enculturation practices and on their parental styles. Ethnic and national affirmations were found to be two independent orientations. Regression analysis showed that the highest explanation of variance came from the adolescent's perception of their relationship with their parents, followed by parental enculturation, and perceived discrimination. The school and peer context explained a lesser amount of variance. Parents' contribution to cultural identity is not limited to the ethnic orientation; parents also contribute in a positive way to national identity. The parents' contribution was different in the case of mothers and fathers. This reflects the dynamic of acculturation within immigrant families. PMID- 17868801 TI - C-reactive protein gene polymorphisms, C-reactive protein blood levels, and cardiovascular disease risk. AB - C-reactive protein (CRP), a blood marker of inflammation and a hallmark of the acute-phase response, has been shown to be a powerful and specific predictor of cardiovascular event risk in populations of otherwise healthy persons. Here we review what is known about CRP gene polymorphisms, discuss how these might affect the epidemiology of CRP and our understanding of CRP's contribution to cardiovascular disease, and examine their potential clinical usefulness. Evidence shows that certain subtle variations in the CRP gene sequence, mostly single nucleotide polymorphisms, predictably and strongly influence the blood level of CRP. Some of these variations are associated with clinical correlates of cardiovascular disease. If future studies can establish with certainty that CRP influences cardiovascular biology, then CRP gene profiling could have clinical utility. PMID- 17868802 TI - Impact of vessel size on outcome after implantation of sirolimus-eluting and paclitaxel-eluting stents: a subgroup analysis of the SIRTAX trial. AB - OBJECTIVES: We assessed the impact of vessel size on angiographic and long-term clinical outcome after percutaneous coronary intervention (PCI) with sirolimus eluting stents (SES) and paclitaxel-eluting stents (PES) within a randomized trial (SIRTAX [Sirolimus-Eluting Stent Compared With Paclitaxel-Eluting Stent for Coronary Revascularization]). BACKGROUND: Percutaneous coronary intervention in small-vessel disease is associated with an increased risk of major adverse cardiac events (MACE). METHODS: A total of 1,012 patients were randomly assigned to treatment with SES (n = 503) or PES (n = 509). A stratified analysis of angiographic and clinical outcome was performed up to 2 years after PCI according to size of the treated vessel (reference vessel diameter < or =2.75 vs. >2.75 mm). RESULTS: Of 1,012 patients, 370 patients (37%) with 495 lesions underwent stent implantation in small vessels only, 504 patients (50%) with 613 lesions in large vessels only, and 138 patients (14%) with 301 lesions in both small and large vessels (mixed). In patients with small-vessel stents, SES reduced MACE by 55% (10.4% vs. 21.4%; p = 0.004), mainly driven by a 69% reduction of target lesion revascularization (TLR) (6.0% vs. 17.7%; p = 0.001) compared with PES at 2 years. In patients with large- and mixed-vessel stents, rates of MACE (large: 10.4% vs. 13.1%; p = 0.33; mixed: 16.7% vs. 18.0%; p = 0.83) and TLR (large: 6.9% vs. 8.6%; p = 0.47; mixed: 16.7% vs. 15.4%; p = 0.86) were similar for SES and PES. There were no significant differences with respect to death and myocardial infarction between the 3 groups. CONCLUSIONS: Compared with PES, SES more effectively reduced MACE and TLR in small-vessel disease. Differences between SES and PES appear less pronounced in patients with large- and mixed-vessel disease. (The SIRTAX trial; http://clinicaltrials.gov/ct/show/NCT00297661?order=1; NCT00297661). PMID- 17868803 TI - Poor responsiveness to clopidogrel: drug-specific or class-effect mechanism? Evidence from a clopidogrel-to-ticlopidine crossover study. AB - OBJECTIVES: This study was designed to investigate whether poor responders to thienopyridines after clopidogrel remain so even after ticlopidine administration (class effect) or whether a drug-specific effect exists between currently available thienopyridines. BACKGROUND: Whether clopidogrel poor responders also display inadequate platelet inhibition after ticlopidine administration remains undefined. METHODS: Platelet aggregation (PA) was measured in 143 patients, while they were taking aspirin, with light transmission aggregometry using adenosine diphosphate as an agonist at baseline (T0) and at clopidogrel steady state (T1). After T1) clopidogrel was stopped and substituted with ticlopidine. Then PA was assessed at ticlopidine steady state (T2). Resistance was defined as an absolute difference between T0 and after-treatment (T1 or T2) PA < or =10%. RESULTS: Clopidogrel and ticlopidine responsiveness was normally distributed; PA at T1 did not differ compared with T2. Thirty (21%) and 28 (19%) patients were clopidogrel and ticlopidine nonresponders, respectively. Only 5 patients (3.5%) were nonresponders to both clopidogrel and ticlopidine (class effect), whereas 25 patients (83%) who were clopidogrel nonresponders at T1 were responsive to ticlopidine, reaching a higher level of platelet inhibition at T2 (PA 69 +/- 15 vs. 44 +/- 18, p < 0.01) (drug-specific response). On the other hand, 23 patients who were responsive to clopidogrel showed resistance to ticlopidine at T2 (PA 46 +/- 15 vs. 70 +/- 15, p < 0.01) (drug-specific response). CONCLUSIONS: Poor responsiveness to either clopidogrel or ticlopidine at steady state was common, whereas nonresponders to both drugs were relatively infrequent (3.5%, 95% confidence interval 1.5% to 7.9%), suggesting that poor response to thienopyridines may frequently be a drug-specific mechanism. PMID- 17868805 TI - Olmesartan, but not amlodipine, improves endothelium-dependent coronary dilation in hypertensive patients. AB - OBJECTIVES: We aimed to compare the effects of the angiotensin II receptor blocker (ARB) olmesartan versus the calcium channel blocker (CCB) amlodipine on coronary endothelial dysfunction in patients with hypertension. BACKGROUND: Angiotensin II receptor blockers are thought to have greater beneficial effects than CCBs on coronary vasomotion by directly blocking action of angiotensin II. METHODS: Twenty-six patients with untreated essential hypertension were prospectively assigned to treatment with either olmesartan (27.7 +/- 12.4 mg/day, n = 13) or amlodipine (5.6 +/- 1.5 mg/day, n = 13) for 12 weeks. Changes of corrected myocardial blood flow (DeltaMBF) and coronary vascular resistance (DeltaCVR) from rest to cold pressor were measured by using 15O-water and positron emission tomography before and after treatment. Blood biomarkers including lipids, glucose, insulin, high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and superoxide dismutase (SOD) were also measured. RESULTS: Olmesartan and amlodipine reduced blood pressure (BP) to the same extent (-28.7 +/- 16.2 mm Hg vs. -26.7 +/- 10.8 mm Hg). In the olmesartan group, DeltaMBF tended to be greater (-0.15 +/- 0.19 ml/g/min vs. 0.03 +/- 0.17 ml/g/min, p = 0.09 by 2-way analysis of variance), and DeltaCVR was significantly decreased (7.9 +/- 23.5 mm Hg/[ml/g/min] vs. -16.6 +/- 18.0 mm Hg/[ml/g/min], p < 0.05) after treatment, whereas these parameters did not change in the amlodipine group (DeltaMBF: -0.15 +/- 0.12 ml/g/min vs. -0.12 +/- 0.20 ml/g/min; DeltaCVR: 6.5 +/- 18.2 mm Hg/[ml/g/min] vs. 4.8 +/- 23.4 mm Hg/[ml/g/min]). Serum SOD activity tended to increase (4.74 +/- 4.77 U/ml vs. 5.57 +/- 4.74 U/ml, p = 0.07 by 2-way analysis of variance) only in the olmesartan group. CONCLUSIONS: Olmesartan, but not amlodipine, improved endothelium-dependent coronary dilation in hypertensive patients independent of BP reduction. These beneficial effects on coronary vasomotion might be via an antioxidant property of ARBs. PMID- 17868804 TI - Two mechanistic pathways for thienopyridine-associated thrombotic thrombocytopenic purpura: a report from the SERF-TTP Research Group and the RADAR Project. AB - OBJECTIVES: We sought to describe clinical and laboratory findings for a large cohort of patients with thienopyridine-associated thrombotic thrombocytopenic purpura (TTP). BACKGROUND: The thienopyridine derivatives, ticlopidine and clopidogrel, are the 2 most common drugs associated with TTP in databases maintained by the U.S. Food and Drug Administration (FDA). METHODS: Clinical reports of TTP associated with clopidogrel and ticlopidine were identified from medical records, published case reports, and FDA case reports (n = 128). Duration of thienopyridine exposure, clinical and laboratory findings, and survival were recorded. ADAMTS13 activity (n = 39) and inhibitor (n = 30) were measured for a subset of individuals. RESULTS: Compared with clopidogrel-associated TTP cases (n = 35), ticlopidine-associated TTP cases (n = 93) were more likely to have received more than 2 weeks of drug (90% vs. 26%), to be severely thrombocytopenic (84% vs. 60%), and to have normal renal function (72% vs. 45%) (p < 0.01 for each). Compared with TTP patients with ADAMTS13 activity >15% (n = 13), TTP patients with severely deficient ADAMTS13 activity (n = 26) were more likely to have received ticlopidine (92.3% vs. 46.2%, p < 0.003). Among patients who developed TTP >2 weeks after thienopyridine, therapeutic plasma exchange (TPE) increased likelihood of survival (84% vs. 38%, p < 0.05). Among patients who developed TTP within 2 weeks of starting thienopyridines, survival was 77% with TPE and 78% without. CONCLUSIONS: Thrombotic thrombocytopenic purpura is a rare complication of thienopyridine treatment. This drug toxicity appears to occur by 2 different mechanistic pathways, characterized primarily by time of onset before versus after 2 weeks of thienopyridine administration. If TTP occurs after 2 weeks of ticlopidine or clopidogrel therapy, therapeutic plasma exchange must be promptly instituted to enhance likelihood of survival. PMID- 17868806 TI - Limitations of ejection fraction for prediction of sudden death risk in patients with coronary artery disease: lessons from the MUSTT study. AB - OBJECTIVES: We determined the contribution of multiple variables to predict arrhythmic death and total mortality risk in patients with coronary disease and left ventricular dysfunction. We then constructed an algorithm to predict risk of mortality and sudden death. BACKGROUND: Many factors in addition to ejection fraction (EF) influence the prognosis of patients with coronary disease. However, there are few tools to use this information to guide clinical decisions. METHODS: We evaluated the relationship between 25 variables and total mortality and arrhythmic death in 674 patients enrolled in the MUSTT (Multicenter Unsustained Tachycardia Trial) study that did not receive antiarrhythmic therapy. We then constructed risk-stratification algorithms to weight the prognostic impact of each variable on arrhythmic death and total mortality risk. RESULTS: The variables having the greatest prognostic impact in multivariable analysis were functional class, history of heart failure, nonsustained ventricular tachycardia not related to bypass surgery, EF, age, left ventricular conduction abnormalities, inducible sustained ventricular tachycardia, enrollment as an inpatient, and atrial fibrillation. The model demonstrates that patients whose only risk factor is EF < or =30% have a predicted 2-year arrhythmic death risk <5%. CONCLUSIONS: Multiple variables influence arrhythmic death and total mortality risk. Patients with EF < or =30% but no other risk factor have low predicted mortality risk. Patients with EF >30% and other risk factors may have higher mortality and a higher risk of sudden death than some patients with EF < or =30%. Thus, risk of sudden death in patients with coronary disease depends on multiple variables in addition to EF. PMID- 17868807 TI - Risk assessment for defibrillator therapy: Il Trittico. PMID- 17868808 TI - Prognostic value of multidetector coronary computed tomographic angiography for prediction of all-cause mortality. AB - OBJECTIVES: The purpose of this study was to examine the association of all-cause death with the coronary computed tomographic angiography (CCTA)-defined extent and severity of coronary artery disease (CAD). BACKGROUND: The prognostic value of identifying CAD by CCTA remains undefined. METHODS: We examined a single center consecutive cohort of 1,127 patients > or =45 years old with chest symptoms. Stenosis by CCTA was scored as minimal (<30%), mild (30% to 49%), moderate (50% to 69%), or severe (> or =70%) for each coronary artery. Plaque was assessed in 3 ways: 1) moderate or obstructive plaque; 2) CCTA score modified from Duke coronary artery score; and 3) simple clinical scores grading plaque extent and distribution. A 15.3 +/- 3.9-month follow-up of all-cause death was assessed using Cox proportional hazards models adjusted for pretest CAD likelihood and risk factors. Deaths were verified by the Social Security Death Index. RESULTS: The CCTA predictors of death included proximal left anterior descending artery stenosis and number of vessels with > or =50% and > or =70% stenosis (all p < 0.0001). A modified Duke CAD index, an angiographic score integrating proximal CAD, plaque extent, and left main (LM) disease, improved risk stratification (p < 0.0001). Patients with <50% stenosis had the highest survival at 99.7%. Survival worsened with higher-risk Duke scores, ranging from 96% survival for 1 stenosis > or =70% or 2 stenoses > or =50% (p = 0.013) to 85% survival for > or =50% LM artery stenosis (p < 0.0001). Clinical scores measuring plaque burden and distribution predicted 5% to 6% higher absolute death rate (6.6% vs. 1.6% and 8.4% vs. 2.5%; p = 0.05 for both). CONCLUSIONS: In patients with chest pain, CCTA identifies increased risk for all-cause death. Importantly, a negative CCTA portends an extremely low risk for death. PMID- 17868809 TI - Computed tomography coronary angiography as an anatomic basis for risk stratification: deja vu or something new? PMID- 17868810 TI - Prognostic value of dipyridamole stress cardiovascular magnetic resonance imaging in patients with known or suspected coronary artery disease. AB - OBJECTIVES: We evaluated the prognostic value of dipyridamole stress cardiovascular magnetic resonance imaging (CMR) in patients with chest pain and known or suspected coronary artery disease. BACKGROUND: Stress perfusion CMR has been incorporated in daily practice. Data on its prognostic value are preliminary. METHODS: Dipyridamole stress CMR was performed in 420 patients with chest pain and known or suspected coronary artery disease. The extent (number of segments according to the 17-segment model) of abnormal wall motion at rest (AWM rest), abnormal wall motion with dipyridamole (AWM-D), perfusion deficit (at stress first-pass perfusion imaging), and delayed enhancement (at late enhancement imaging) were analyzed. RESULTS: During a median follow-up of 420 days, 41 major adverse cardiac events (MACE), including 9 cardiac deaths, 14 nonfatal myocardial infarctions, and 18 readmissions for unstable angina with documented abnormal angiography, were documented. The MACE were more frequent in patients with significant (>1 segment) AWM-rest (22% vs. 5%), AWM-D (21% vs. 4%), perfusion deficit (17% vs. 5%), and delayed enhancement (20% vs. 6%; p <0.0001 in all cases). In a multivariate analysis adjusted for baseline characteristics, the extent of AWM-D was independently related to MACE (hazard ratio [HR] 1.15 [95% confidence interval (CI) 1.06 to 1.24] per segment; p = 0.0006) and to major events (cardiac death or nonfatal myocardial infarction; HR 1.15 [95% CI 1.05 to 1.26] per segment; p = 0.002). CONCLUSIONS: Dipyridamole stress CMR is useful for predicting the outcome of patients with known or suspected coronary artery disease. PMID- 17868811 TI - Speckle-tracking radial strain reveals left ventricular dyssynchrony in patients with permanent right ventricular pacing. AB - OBJECTIVES: Speckle-tracking strain analysis was used to assess the effects of permanent right ventricular (RV) pacing on the heterogeneity in timing of regional wall strain and left ventricular (LV) dyssynchrony. BACKGROUND: Recent studies have shown detrimental effects of RV pacing, possibly related to the induction of LV dyssynchrony. METHODS: Fifty-eight patients treated with His bundle ablation and pacemaker implantation were studied. To assess the effect of RV pacing on time-to-peak radial strain of different LV segments, we applied speckle-tracking analysis to standard LV short-axis images. In addition, New York Heart Association (NYHA) functional class, LV volumes, and systolic function were assessed at baseline and after long-term RV pacing. RESULTS: At baseline, similar time-to-peak strain for the 6 segments was observed (mean 371 +/- 114 ms). In contrast, after a mean of 3.8 +/- 2.0 years of RV pacing, there was a marked heterogeneity in time-to-peak strain of the 6 segments. In 33 patients (57%), LV dyssynchrony, represented by a time difference > or =130 ms between the time-to peak strain of the (antero)septal and the posterolateral segments, was present. In these patients, a deterioration of LV systolic function and NYHA functional class was observed. In 11 patients, an "upgrade" of the conventional pacemaker to a biventricular pacemaker resulted in partial reversal of the detrimental effects of RV pacing. CONCLUSIONS: Speckle-tracking analysis revealed that permanent RV pacing induced heterogeneity in time-to-peak strain, resulting in LV dyssynchrony in 57% of patients, associated with deterioration of LV systolic function and NYHA functional class. Biventricular pacing may reverse these adverse effects of RV pacing. PMID- 17868812 TI - Transcatheter closure of perimembranous ventricular septal defects: early and long-term results. AB - OBJECTIVES: We sought to analyze safety, efficacy, and follow-up results of percutaneous closure of perimembranous ventricular septal defects (pmVSD). BACKGROUND: Results of pmVSD transcatheter closure have been reported in the literature; however, follow-up data are still limited. METHODS: Between January 1999 and June 2006, 104 patients underwent percutaneous closure of a pmVSD at our institution. An Amplatzer VSD device (muscular or eccentric) (AGA Medical Corp., Golden Valley, Minnesota) was used in all subjects. RESULTS: The mean age at closure was 14 years (range 0.6 to 63 years). The attempt to place a device was successful in 100 patients (96.2%). The median device size used was 8 mm (range 4 to 16 mm). No deaths occurred. Total occlusion rate was 47% at completion of the procedure, rising to 84% at discharge and 99% during the follow-up. A total of 13 early complications occurred (11.5%), but in all but 2 subjects (1.9%) these were transient. The median follow-up was 38.5 months. The most significant complication was complete atrioventricular block (cAVB), which required pacemaker implantation in 6 subjects (5.7%; 2 in the early phase and 4 during the follow up). Cox proportional hazards regression analysis showed that the only variable significantly associated with the occurrence of this complication was age at the time of the procedure (p = 0.028; relative risk 0.25). All subjects experiencing this problem were <6 years old. CONCLUSIONS: In the current era and in experienced hands, pmVSD closure can be performed safely and successfully. The major concern is the occurrence of cAVB; therefore, very careful monitoring of rhythm is mandatory during follow-up. PMID- 17868813 TI - Permanent pacemaker for atrioventricular conduction block after operative repair of perimembranous ventricular septal defect. AB - OBJECTIVES: This study sought to discover the incidence of permanent pacemaker (PPM) placement for atrioventricular conduction block (AV block) after operative repair of perimembranous ventricular septal defect (PMVSD) in a large multi institutional database and in the subgroup of patients comparable to those considered for transcatheter device closure of PMVSD. BACKGROUND: Atrioventricular conduction block is a complication of operative repair of PMVSD and of device closure of this defect. Earlier reports do not report the incidence of AV block by VSD type. METHODS: The Pediatric Cardiac Care Consortium database was searched for all children who had operative PMVSD repair except those with abnormalities that increase risk of AV block. The patient group was searched for those with subsequent PPM placement for AV block. Demographic data and time to PPM placement were available for all patients. RESULTS: Of 4,432 patients with PMVSD repair, 48 (1.1%) underwent PPM placement for AV block. The PPM group was more likely to have Down syndrome (41% vs. 18%; p < 0.001), was younger (mean age 14 vs. 26 months; p < 0.001), and had longer mean length of postoperative hospital stays (20 vs. 8 days; p < 0.001). The most significant risk factor for AV block was Down syndrome (odds ratio 3.62, 95% confidence interval 2.02 to 6.39; p < 0.005). Modal time to PPM placement was 7 days (range 0 to 4,078 days). Out of 1,877 patients comparable to those currently considered for device closure, 13 (0.8%) underwent PPM placement after PMVSD repair. CONCLUSIONS: Operative AV block and PPM placement occurred in 1.1% of patients in the total group and in 0.8% of patients comparable to those considered for device closure of PMVSD. A PPM placement is more likely in patients with Down syndrome. These data should be considered as devices are developed and in the future when counseling families about options for PMVSD closure. PMID- 17868814 TI - Medicine in blink. PMID- 17868815 TI - Cardiovascular prevention in asymptomatic diabetic patients. PMID- 17868817 TI - Energy and transport. AB - We examine the links between fossil-fuel-based transportation, greenhouse-gas emissions, and health. Transport-related carbon emissions are rising and there is increasing consensus that the growth in motorised land vehicles and aviation is incompatible with averting serious climate change. The energy intensity of land transport correlates with its adverse health effects. Adverse health effects occur through climate change, road-traffic injuries, physical inactivity, urban air pollution, energy-related conflict, and environmental degradation. For the world's poor people, walking is the main mode of transport, but such populations often experience the most from the harms of energy-intensive transport. New energy sources and improvements in vehicle design and in information technology are necessary but not sufficient to reduce transport-related carbon emissions without accompanying behavioural change. By contrast, active transport has the potential to improve health and equity, and reduce emissions. Cities require safe and pleasant environments for active transport with destinations in easy reach and, for longer journeys, public transport that is powered by renewable energy, thus providing high levels of accessibility without car use. Much investment in major road projects does not meet the transport needs of poor people, especially women whose trips are primarily local and off road. Sustainable development is better promoted through improving walking and cycling infrastructures, increasing access to cycles, and investment in transport services for essential needs. Our model of London shows how increased active transport could help achieve substantial reductions in emissions by 2030 while improving population health. There exists the potential for a global contraction and convergence in use of fossil-fuel energy for transport to benefit health and achieve sustainability. PMID- 17868818 TI - Food, livestock production, energy, climate change, and health. AB - Food provides energy and nutrients, but its acquisition requires energy expenditure. In post-hunter-gatherer societies, extra-somatic energy has greatly expanded and intensified the catching, gathering, and production of food. Modern relations between energy, food, and health are very complex, raising serious, high-level policy challenges. Together with persistent widespread under nutrition, over-nutrition (and sedentarism) is causing obesity and associated serious health consequences. Worldwide, agricultural activity, especially livestock production, accounts for about a fifth of total greenhouse-gas emissions, thus contributing to climate change and its adverse health consequences, including the threat to food yields in many regions. Particular policy attention should be paid to the health risks posed by the rapid worldwide growth in meat consumption, both by exacerbating climate change and by directly contributing to certain diseases. To prevent increased greenhouse-gas emissions from this production sector, both the average worldwide consumption level of animal products and the intensity of emissions from livestock production must be reduced. An international contraction and convergence strategy offers a feasible route to such a goal. The current global average meat consumption is 100 g per person per day, with about a ten-fold variation between high-consuming and low consuming populations. 90 g per day is proposed as a working global target, shared more evenly, with not more than 50 g per day coming from red meat from ruminants (ie, cattle, sheep, goats, and other digastric grazers). PMID- 17868819 TI - Policies for accelerating access to clean energy, improving health, advancing development, and mitigating climate change. AB - The absence of reliable access to clean energy and the services it provides imposes a large disease burden on low-income populations and impedes prospects for development. Furthermore, current patterns of fossil-fuel use cause substantial ill-health from air pollution and occupational hazards. Impending climate change, mainly driven by energy use, now also threatens health. Policies to promote access to non-polluting and sustainable sources of energy have great potential both to improve public health and to mitigate (prevent) climate disruption. There are several technological options, policy levers, and economic instruments for sectors such as power generation, transport, agriculture, and the built environment. However, barriers to change include vested interests, political inertia, inability to take meaningful action, profound global inequalities, weak technology-transfer mechanisms, and knowledge gaps that must be addressed to transform global markets. The need for policies that prevent dangerous anthropogenic interference with the climate while addressing the energy needs of disadvantaged people is a central challenge of the current era. A comprehensive programme for clean energy should optimise mitigation and, simultaneously, adaption to climate change while maximising co-benefits for health--eg, through improved air, water, and food quality. Intersectoral research and concerted action, both nationally and internationally, will be required. PMID- 17868820 TI - Energy, energy efficiency, and the built environment. AB - Since the last decades of the 19th century, technological advances have brought substantial improvements in the efficiency with which energy can be exploited to service human needs. That trend has been accompanied by an equally notable increase in energy consumption, which strongly correlates with socioeconomic development. Nonetheless, feasible gains in the efficiency and technology of energy use in towns and cities and in homes have the potential to contribute to the mitigation of greenhouse-gas emissions, and to improve health, for example, through protection against temperature-related morbidity and mortality, and the alleviation of fuel poverty. A shift towards renewable energy production would also put increasing focus on cleaner energy carriers, especially electricity, but possibly also hydrogen, which would have benefits to urban air quality. In low income countries, a vital priority remains the dissemination of affordable technology to alleviate the burdens of indoor air pollution and other health effects in individuals obliged to rely on biomass fuels for cooking and heating, as well as the improvement in access to electricity, which would have many benefits to health and wellbeing. PMID- 17868821 TI - The built environment and health. PMID- 17868826 TI - Health care needs of patients with obstructive lung diseases. PMID- 17868827 TI - Properties and microstructure of protein-based film from round scad (Decapterus maruadsi) muscle as affected by palm oil and chitosan incorporation. AB - The properties of protein-based film prepared from round scad (Decapterus maruadsi) muscle in the absence and the presence of palm oil and/or chitosan were investigated. Films added with 25% palm oil (as glycerol substitiution) had the slight decrease in water vapor permeability (WVP) and elongation at break (EAB) (p<0.05). WVP and tensile strength (TS) of films increased but EAB decreased when 10-40% chitosan (as protein substitution) was incorporated (p<0.05). Hydrophobic interactions and hydrogen bonds, together with disulfide and non-disulfide covalent bonds, played an important role in stabilizing the film matrix. The a* and b*-values increased with increasing chitosan levels (p<0.05). Films added with chitosan were less transparent and had the lowered transmission in the visible range. The incorporation of 25% palm oil and 40% chitosan yielded the films with the improved TS but decreased water vapor barrier property. Apart from film strengthening effect, chitosan inconjunction with Tween-20 most likely functioned as the emulsifier/stabilizer in film forming solution containing palm oil. PMID- 17868828 TI - Good time for a bad shoulder. PMID- 17868829 TI - Arthroscopically assisted ankle fusion in patients with end-stage tuberculosis. AB - PURPOSE: Our purpose was to evaluate the clinical outcomes of arthroscopically assisted ankle fusion in patients with end-stage tuberculosis. METHODS: Ten patients, all with end-stage tuberculosis, were operated on by arthroscopically assisted ankle fusion, and a half-ring sulcated external fixator was used. Partial weight-bearing was started on the fourth day. The clinical results were assessed with the American Orthopaedic Foot & Ankle Society score. Ankle fusion was proved by radiographs. RESULTS: At the mean follow-up of 23 months, all fusions were healed; the mean time to radiologic healing was 14.5 weeks. The final American Orthopaedic Foot & Ankle Society score was 66 points. CONCLUSIONS: Arthroscopically assisted debridement and ankle arthrodesis with an external fixator provided a very satisfactory rate of ankle fusion in 10 patients who had no recurrences or other complications. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 17868830 TI - Mechanical chondroplasty: early metabolic consequences in vitro. AB - PURPOSE: The purpose of this study was to determine the depth of penetration from mechanical chondroplasty and metabolic consequences of this procedure on the remaining articular cartilage. METHODS: Mechanical chondroplasty was performed in vitro on a portion of fresh grade I or II articular cartilage from 8 human knee arthroplasty specimens. Treated and control (untreated) explants (approximately 30 mg) were cut from the cartilage. The explants were divided into 2 groups, day 1 and day 4, placed separately in a 48-well plate containing media, and incubated at 37 degrees C for 24 hours. After the 24-hour incubation, the explants were weighed on day 1 and day 4, and explant media were removed and tested for total proteoglycan synthesis and aggrecan synthesis. At time 0, 2 sets (2.6 mm each) of treated and control cartilage slices were cut with a precision saw. One set was stained for confocal laser microscopy via a cytotoxicity stain to determine cell viability. The second set was stained with H&E to determine depth of penetration. RESULTS: The mean depth of penetration was 252.8 +/- 78 microm. There was no significant difference (P > .25) between total proteoglycan synthesis for control versus treatment groups on day 1 or 4. Aggrecan synthesis was significantly reduced on day 1 when normalized for tissue weight (P = .019) and double-stranded deoxyribonucleic acid (P = .004). On day 4, no significant difference was detected. Confocal laser microscopy did not show cell death below the zone of treatment. CONCLUSIONS: There was no significant metabolic consequence caused by chondroplasty to the remaining articular cartilage, and the zone of injury was limited to the treatment area. CLINICAL RELEVANCE: Mechanical chondroplasty causes no significant metabolic consequences to articular cartilage under these conditions. PMID- 17868831 TI - Long-term follow-up of surgically treated localized pigmented villonodular synovitis of the knee. AB - PURPOSE: The purpose of this study was to review a single institution's large consecutive series of localized pigmented villonodular synovitis (PVNS) of the knee. METHODS: Cases for review were identified by a search of our institution's pathology records for definitive diagnoses of monoarticular localized PVNS (LPVNS) of the knee between 1970 and 1996. Patients' presenting symptoms and examination were recorded, as were the preoperative diagnosis and documentation of the PVNS nodule's location in the knee at surgery. Eighty-four patients were diagnosed with localized PVNS of the knee during the study period. Twenty-nine of these cases were incidental findings associated with planned total knee replacement and were excluded from the study. Of the remaining 55 patients constituting the study subgroup, 26 have been reviewed in detail. RESULTS: There were 15 males and 11 females, and the mean age at presentation was 36.7 years. Patients presented for evaluation at an average of 15 months after the onset of symptoms. Pain was the most common complaint, reported by 24 of the 26. Locking and giving way were reported by 10 and 5 patients, respectively. On examination, 13 patients had an effusion, 11 had joint line tenderness, and 10 had a palpable mass. The most common preoperative diagnosis was a meniscus tear (10 of the 26), followed by PVNS (4), "mass" (4), and anterior cruciate ligament injury (3). At surgery, the nodule of PVNS was found most frequently in the suprapatellar pouch (6 cases), followed by the femoral notch (4), lateral synovium/gutter (4), popliteal fossa (3), lateral compartment (3), and medial compartment (2). Fourteen of the procedures performed were open, and 12 were performed by arthroscopy. Ten of the 26 patients participated in a long-term follow-up via the Lysholm Knee Scoring Scale questionnaire (average, 65.8 months postoperatively; average score, 95.4/100). Of these 10, 7 returned for follow-up clinical examinations (6 excellent results and 1 good). All 10 patients were operated on arthroscopically, and none required repeat surgery. CONCLUSIONS: This review represents the largest series of localized PVNS of the knee to date. Echoing the findings of other PVNS studies, patients presented, on average, in their fourth decade. The common preoperative diagnosis of a meniscal tear is not surprising given the frequent presentation of a painful and, typically, locking knee with joint line tenderness and effusion. Interestingly, what is perhaps the most diagnostic finding on examination, a palpable mass, was present in only 1 of the 6 patients who had PVNS in the most common location, the suprapatellar pouch. With the ease and utility of modern arthroscopy, however, PVNS is an easily treatable condition that can be diagnosed at the time of surgery. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 17868832 TI - Current techniques in anatomic anterior cruciate ligament reconstruction. AB - PURPOSE: The aim of this report is to summarize several techniques that are currently performed to reconstruct the anterior cruciate ligament (ACL) via an anatomic approach restoring the anteromedial (AM) bundle and posterolateral (PL) bundle separately. METHODS: A survey containing questions about technique and rehabilitation protocol and a picture of an anatomic specimen, where study participants were asked to locate the tunnels, was created. This was sent to surgeons identified either through an Internet-based search via the National Library of Medicine or who have presented clinical studies about anatomic ACL reconstruction at international meetings. The questions were presented in an open fashioned way in an Excel-based data file (Microsoft, Redmond, WA) and addressed the profile of the panelists, number of total and anatomic ACL reconstruction per year, graft choice, graft fixation, advantages and disadvantages of anatomic ACL reconstruction, and rehabilitation protocol. RESULTS: One of the most common techniques used 2 femoral and 2 tibial tunnels with a soft-tissue graft. All but 1 panelist used a hamstring graft. A great variance in tunnel placement of the PL bundle was noted. Most surgeons prefer a transtibial technique for the AM bundle. Of the study participants, 67% start by placing a tunnel at the tibial insertion of the ACL. All of the surgeons who started at the femoral insertion with the PL bundle used an accessory medial portal technique. CONCLUSIONS: Anatomic reconstruction of the ACL remains a technically demanding procedure. Hamstring grafts are the most commonly used graft; an extracortical flip button technique is used at the femoral site, and a hybrid technique is used at the tibial site. The femoral tunnel placement of the PL bundle tunnel is statistically different from the AM bundle tunnel, and the same rehabilitation protocols as for single bundle ACL reconstructions are used. CLINICAL RELEVANCE: Knowledge of the pitfalls and current techniques used for an anatomic approach restoring both bundles of the ACL may provide important information for surgeons considering this technique. LEVEL OF EVIDENCE: Level V, expert opinion. PMID- 17868833 TI - An arthroscopic treatment regimen for osteoarthritis of the knee. AB - PURPOSE: The purpose of this study was to evaluate the functional and subjective outcomes of patients with moderate to severe osteoarthritis of the knee who underwent a comprehensive arthroscopic treatment regimen. METHODS: Between August 2000 and November 2001, 69 knees in 61 patients were treated with an arthroscopic regimen. Inclusion criteria included severe osteoarthritis and a minimum 2-year follow-up. Arthroscopic treatment included joint insufflation, lysis of adhesions, anterior interval release, contouring of cartilage defects to a stable rim, shaping of meniscus tears to a stable rim, synovectomy, removal of loose bodies, and removal of osteophytes that affected terminal extension. Exclusion criteria included the treatment of chondral defects with microfracture. Failure was defined as knees requiring arthroplasty because this was what patients were trying to avoid. RESULTS: The average patient age was 57 (range, 37-78), with 35 men and 26 women. Patients had an average of 1.5 previous surgeries (range, 0 12). The average preoperative Lysholm score was 49 (range, 14-79). On average, knees were insufflated with 170 mL of lactated Ringer's solution (range, 120 240). Nine knees failed, with survivorship of 83% at 3 years. At an average follow-up of 31 months (range, 24-41), the average Lysholm score was 74 (range, 37-100), with an average improvement of 25 points. The average Tegner score was 4 (range, 0-8). Average patient satisfaction was 8 (range, 1-10). The average Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain score was 4 (range, 0-14), WOMAC stiffness was 2 (range, 0-4), and WOMAC function was 11 (range, 0-44). Independent predictors of improvement in Lysholm score included a shift in the weight-bearing axis and preoperative Lysholm score. CONCLUSIONS: This arthroscopic treatment regimen can improve function and activity levels in patients with moderate to severe osteoarthritis. Of 69 patients, 60 (87%) patients had a satisfactory result. However, in this group of 60, 11 patients needed a second procedure, resulting in a 71% satisfactory result after 1 surgery. LEVEL OF EVIDENCE: Level IV, therapeutic case series. PMID- 17868834 TI - Prevalence of saphenous nerve injury after autogenous hamstring harvest: an anatomic and clinical study of sartorial branch injury. AB - PURPOSE: Injury to the sartorial (terminal) branch of the saphenous nerve (SBSN) has received little attention in the literature, despite its anatomic proximity to the hamstring tendons during autogenous harvesting. This study aims to define the prevalence of saphenous nerve injury after anterior cruciate ligament (ACL) reconstruction with autogenous hamstrings and define clinically relevant anatomy that may contribute to nerve injury. METHODS: Surveys regarding the presence and duration of sensory changes in the infrapatellar branch of the saphenous nerve (IPBSN) and SBSN were retrospectively sent to 164 patients who had undergone arthroscopically assisted ACL reconstruction with hamstring autograft over a 4 year period. Eleven cadavers were then dissected to identify the relation of the saphenous nerve to the hamstring tendons and accessory insertions. RESULTS: Postoperative sensory disturbance was present in 74% of patients surveyed. Concomitant injuries to both the SBSN and IPBSN occurred in 32% of patients, whereas isolated paresthesias in the SBSN and IPBSN distribution affected 23% and 19%, respectively. The saphenous nerve was intimately associated with the gracilis for 4.6 cm in the distal thigh, from 7.2 cm (range, 6.4 to 9.3 cm) to 11.8 cm (range, 7 to 13.2 cm) proximal to its insertion. Accessory hamstring insertions were present distal to the point where the sartorial branch became extrafascial. CONCLUSIONS: The SBSN is at higher risk of injury during hamstring ACL reconstruction than has been previously reported. The saphenous nerve is intimately involved with the gracilis tendon for a portion of its course in the distal thigh, likely predisposing it to damage during passage of the tendon stripper. LEVEL OF EVIDENCE: Level IV. PMID- 17868835 TI - Olecranon fractures repaired with FiberWire or metal wire tension banding: a biomechanical comparison. AB - PURPOSE: Tension band constructs are commonly used for olecranon fracture fixation. The purpose of this study was to determine if a tension band constructed of FiberWire (Arthrex, Naples, FL), a high-strength polyester and polyethylene suture, will provide fixation that is equivalent to an 18-gauge metal wire tension band. METHODS: The following 4 fixation methods were biomechanically tested in cadaveric elbows with a simulated transverse olecranon fracture: (1) Kirschner wires (K-wires) with an 18-gauge metal wire tension band, (2) K-wires with a FiberWire tension band, (3) intramedullary screw with an 18 gauge metal wire tension band, and (4) intramedullary screw with a FiberWire tension band. Each elbow underwent all 4 repair methods. The K-wire repairs were performed first followed by the intramedullary screw repairs. The order of the tension band (FiberWire or metal wire) was randomly assigned. Specimens were tested under cyclic loading conditions that simulated stresses generated by (1) active range of motion and (2) pushing up from a chair. Fracture displacement was recorded by using transducers placed at the articular surface of the fracture and on the posterior surface of the olecranon. RESULTS: There were no significant differences in fracture displacement associated with the use of a high-strength suture or metal wire tension band under conditions simulating active range of motion or a more vigorous physiologic stress. Also, there were no significant differences associated with the use of an intramedullary screw versus K-wire fixation under either condition. CONCLUSIONS: The biomechanical characteristics of high-strength suture tension bands are equivalent to 18-gauge metal wire tension bands when used with either an intramedullary screw or K-wires. The fatigue patterns of high-strength suture tension bands and metal wire tension bands are similar. There is not a significant difference between the biomechanical strength of intramedullary screw fixation constructs and K-wire constructs. CLINICAL RELEVANCE: FiberWire tension bands may be used in place of metal wire tension bands without sacrificing fixation strength. PMID- 17868836 TI - The inter-rater reliability of shoulder arthroscopy. AB - PURPOSE: The purpose of this study was to determine the inter-rater reliability of orthopaedic shoulder surgeons in evaluating the intra-articular structures involved in real-time diagnostic shoulder arthroscopy by use of a videotape model. METHODS: Twenty patients (nineteen male patients and one female patient) diagnosed with recurrent anterior shoulder instability with a mean age of 27.9 years (range, 15 to 44 years) consented to participate in the study. Standardized diagnostic shoulder arthroscopies (modified Snyder protocol) were done by a single experienced surgeon, and the procedures were videotaped. The patients' clinical information, radiographs, and videotape of the arthroscopy were sent to 6 experienced shoulder surgeons. The surgeons reviewed the clinical information, assessed the intra-articular structures shown on the videotape, and recorded their diagnoses on a standardized data collection form. The primary outcome was the median overall percent agreement for the video review surgeons by structure evaluated. RESULTS: The median values for overall agreement for the video review surgeons were as follows: anterior labrum, 90%; inferior labrum, 75%; superior labrum, 60%; posterior labrum, 65%; superior glenohumeral ligament, 50%; middle glenohumeral ligament, 50%; anterior inferior glenohumeral ligament, 25%; glenoid surface, 35%; detection of Hill-Sachs lesion, 85%; biceps tendon, 70%; supraspinatus tendon, 85%; infraspinatus tendon, 70%; and subscapularis tendon, 80%. CONCLUSIONS: The inter-rater reliability for orthopaedic shoulder surgeons' arthroscopic assessment of intra-articular anatomy in patients with anterior shoulder instability varied by structure examined. It was very good (>80%) for the anterior labrum and supraspinatus tendon and in detecting a Hill-Sachs lesion, poor (<40%) for the glenoid and anterior inferior glenohumeral ligament, and intermediate for all other structures examined. LEVEL OF EVIDENCE: Level V, diagnostic study, expert opinion. PMID- 17868837 TI - Vascular anatomy of the subacromial space: a map of bleeding points for the arthroscopic surgeon. AB - PURPOSE: Our purpose was to study the vascular anatomy of the subacromial space and to map the major sources of expected bleeding during subacromial arthroscopy surgery. METHODS: Ten shoulders of five adult cadavers underwent whole-body arterial perfusion with a mixture of lead oxide, gelatin, and water. The tissue specimens were dissected, photographed, radiographed, scanned, and analyzed with a digital software analyzer. Dissection of the arteries of the subacromial space, with their respective anatomic landmarks, was documented. Correlations of bleeding areas during subacromial arthroscopic surgery and cadaveric dissection were carried out. A vascular map of the walls of the subacromial space was created. RESULTS: The vascularity of the subacromial structures showed consistent patterns of distribution in 60% of the shoulders dissected, and specific sources of bleeding were analyzed. We divided this space into walls with their major arteries as follows: anterior wall, with the acromial branch of the thoracoacromial artery; posterior wall, with the posteromedial acromial branch of the suprascapular artery; and medial wall, with the anterior and posterior arteries of the acromioclavicular joint. The vascular map of the lateral wall, roof, and floor of the subacromial space was also described. CONCLUSIONS: Vascular maps of the arteries of the walls of the subacromial space were created. The subacromial space is highly vascular, and the pattern of blood supply was found to be constant in 60% of the shoulders dissected. This knowledge of the vascular anatomy may decrease bleeding during surgery. CLINICAL RELEVANCE: Knowledge of the vascular anatomy may decrease vascular damage during subacromial arthroscopy surgery. PMID- 17868838 TI - A comparison of the spectrum of intra-articular lesions in acute and chronic anterior shoulder instability. AB - PURPOSE: The purpose of the study was to compare the incidence of secondary intra articular shoulder lesions in patients with acute and chronic anterior shoulder instability. The occurrence of glenoid shape alterations (inverted pear glenoid) in recurrent instability was especially examined. METHODS: Data for all arthroscopically ascertained intra-articular shoulder lesions in a series of 127 patients with acute and chronic traumatic anterior instability were recorded. RESULTS: Hemarthrosis was evident in all patients with acute dislocation and in 7 patients with chronic laxity who underwent surgery shortly after a dislocation episode. In both groups the presence of a chondral or osteochondral Hill-Sachs lesion was noted in 112 patients (88.1%), a Bankart lesion was noted in 106 patients (83.46%), an anterior labroligamentous periosteal sleeve avulsion (ALPSA) lesion was noted in 13 patients (10.23%), a SLAP lesion was noted in 26 patients (20.47%), a humeral avulsion of the glenohumeral ligament (HAGL) lesion was noted in 2 acutely dislocated shoulders (1.57%), and capsular laxity was noted in 33 patients (25.98%). All ALPSA lesions were noted in patients with chronic instability (P = .044), and both HAGL lesions were found in patients with acute dislocations (P = .002). In patients with acute dislocations the incidence of Bankart lesions was 78.2% (18/23), whereas in chronic cases the incidence of Bankart or ALPSA lesions was 97.11% (101/104) (P = .002). In the group with acute dislocations there was a Hill-Sachs lesion in 15 cases (65.21%) and chronic recurrent instability accounted for 97 cases (93.26%) (P = .001). The capsule was considered lax in 2 patients with acute instability and 31 patients with chronic instability (8.69% v 29.8%, P = .037). The overall frequency of SLAP lesions was not statistically significant between acute and chronic cases (P = .868), unlike their distribution. In acute cases there were 3 type I and 2 type II SLAP lesions, whereas in chronic cases there were 4 type I, 13 type II, 3 type III, and 1 type IV SLAP lesions. Loose bodies were found and removed in 17 chronic and 4 acute cases (16.34% v 13.04%, P = .903). A partial-thickness articular rotator cuff tear was found in 14 patients: 12 with chronic dislocations and 2 with acute dislocations (11.53% v 8.69%, P = .694). The cuff tears were partial articular surface tears, involving less than 25% of the cuff thickness, and were treated with debridement, and cuff repair was not necessary in any case. The inverted pear configuration of the glenoid was found in 16 cases with chronic instability (15.38%), whereas no patient with an acutely dislocated shoulder had an inverted pear-shaped glenoid (P = .044). CONCLUSIONS: Associated, secondary intra articular lesions are more frequent in patients with chronic compared with acute shoulder instability, probably as a result of the repeated dislocation or subluxation episodes. LEVEL OF EVIDENCE: Level IV, prognostic case series. PMID- 17868839 TI - Posterior shoulder pain: a dynamic study of the spinoglenoid ligament and treatment with arthroscopic release of the scapular tunnel. AB - PURPOSE: The purpose of this study was to determine the pressure exerted on the suprascapular nerve by compression of the spinoglenoid ligament during glenohumeral range of motion. In addition, a 2-portal technique was described to arthroscopically visualize and safely release the spinoglenoid ligament while visualizing the suprascapular nerve, artery, and vein. METHODS: Ten cadaveric shoulders were used for visual observation of variation in the position and tension of the spinoglenoid ligament. In 15 additional shoulders, a transducer was used to sense the pressure changes and was recorded in voltage. Pressure changes created by the spinoglenoid ligament on the distal suprascapular nerve in the scapular tunnel during glenohumeral motion were recorded. RESULTS: Internal rotation, rather than external rotation, in any position of the shoulder created a visual increase of tension in the spinoglenoid ligament. Increased pressure readings were noted with internal rotation and with 90 degrees of abduction, full abduction, and full adduction of the shoulder. The suprascapular nerve occupying the space created by the spinoglenoid ligament experiences an increased pressure during glenohumeral range of motion and positions that mimic overhead throwing. The dynamic nature of the ligament with its insertion on the posterior capsule required a new minimally invasive technique for its release that can be safe and straightforward. CONCLUSIONS: The spinoglenoid ligament was affected by the position of the glenohumeral joint. These changes in pressure in combination with repetitive shoulder movement are likely components that cause repeated trauma or compression on the distal suprascapular nerve created by a scapular tunnel syndrome. The surgical technique provides a treatment option when conservative treatment fails in the patient with posterior shoulder pain. CLINICAL RELEVANCE: The spinoglenoid ligament was affected by the position of the shoulder, with the most pressure noted with the arm in full adduction and internal rotation. This pressure can be treated with arthroscopic release. PMID- 17868840 TI - The anatomy and function of the low posterolateral portal in addressing posterior labral pathology. AB - PURPOSE: A standard posterior portal allows excellent visualization of the glenohumeral joint but is inadequate for anchor placement because of its parallelism to the glenoid surface. The purpose of this study was to describe the low posterolateral portal for glenohumeral arthroscopy, describe the anatomy of the portal and surrounding structures, and discuss the portal's usefulness in addressing posterior and inferior shoulder pathology. METHODS: Five cadaveric shoulders were dissected after placement of a spear through the low posterolateral portal. The location was identified via a spinal needle, 2 to 4 cm lateral and 4 to 5 cm inferior to the posterolateral corner of the acromion. Measurements from the spear to the anatomic structures were recorded with a caliper. Seventeen patients with posterior labral pathology were included in this study. The low posterolateral portal was established while visualizing through the anterosuperolateral or posterior portal. The spear and anchor were inserted through the low posterolateral portal. RESULTS: Five shoulders were dissected, and the neurovascular structures relative to the low posterolateral portal were identified. The portal was 13.8 +/- 1.6 mm from the axillary nerve and 13.4 +/- 1.2 mm from the posterior humeral circumflex artery. In the retrospective review the low posterolateral portal was created without difficulty or complication in all 17 patients. The portal was extremely helpful for anchor insertion in the posteroinferior glenoid. It was useful in suture passage through the posterior and inferior labrum and in suture management. CONCLUSIONS: The low posterolateral portal provides the optimal angle for insertion of instruments and anchors, resulting in a more anatomic repair. CLINICAL RELEVANCE: The standard 3 portals are not optimal for approaching posterior and inferior labral tears, and use of the low posterolateral portal improves access and treatment. PMID- 17868841 TI - Continuous infusion of a local anesthetic versus interscalene block for postoperative pain control after arthroscopic shoulder surgery. AB - PURPOSE: The purpose of this investigation was to evaluate the efficacy, complication rate, and cost of a 1-time interscalene block compared with a continuous infusion of a local anesthetic for postoperative pain relief in patients having arthroscopic shoulder surgery. METHODS: After prospective power analysis and institutional review board approval, 56 consecutive patients having arthroscopic shoulder surgery under general anesthesia performed by a single surgeon were randomly assigned to 1 of 2 groups to evaluate postoperative pain control. Group 1 patients received a preoperative interscalene block, and group 2 patients received a subacromial continuous infusion of a local anesthetic (0.5% bupivacaine) via a pain pump for 48 hours postoperatively. Pain was evaluated at 12, 24, 36, and 48 hours and then daily on postoperative days 3 through 7 by use of a visual analog scale included in a patient diary. Patients were provided with 2 "rescue" medication options: ibuprofen and Percocet (Endo Pharmaceuticals, Chadds Ford, PA). The total number of tablets ingested was also evaluated over these same intervals. Total hospital outpatient surgical costs for each group were calculated by dividing total hospital charges by the ratio of annual hospital cost to charges. RESULTS: No statistically significant differences were identified between the 2 groups with regard to visual analog scale pain scores, medication intake, or cost. Complications did not occur in either group. One patient inadvertently removed the pain pump catheter. CONCLUSIONS: Our results support the null hypothesis. We found no difference between interscalene block versus continuous subacromial infusion of a local anesthetic with regard to efficacy, complication rate, or cost. LEVEL OF EVIDENCE: Level I, prospective, randomized controlled trial. PMID- 17868842 TI - Anatomic variations in the long head of biceps: contribution to shoulder dysfunction. AB - The long head of the biceps (LHB) is a subject of interest to shoulder surgeons and physiotherapist alike. Since the advent of shoulder arthroscopy, knowledge of and interest in the LHB has increased. We discuss the current knowledge on anatomic variants of the LHB. Several cadaveric studies have refined the standard textbook description of the LHB origin, showing that it originates from the superior glenoid labrum and the supraglenoid tubercle. These studies have provided important information for the assessment of the LHB, guiding the treatment of lesions such as superior labral anterior posterior (SLAP) tears. Described variants to the anterosuperior glenoid labrum should be noted, from the superior sublabral recess to the Buford complex. Congenital absence of the LHB should be appreciated. Only 4 previous cases have been reported. We have experience in treating 3 further cases. Further information on the function of the LHB has been gleaned from electomyographic, cadaveric, and clinical studies. These have shown that it has a role in stabilizing the humeral head. It has been stated that it may have a proprioceptive function. Classification systems for symptomatic LHB lesions and congenital absence of the LHB tendon are proposed. The management of LHB lesions is also discussed. PMID- 17868843 TI - Arthroscopic debridement and capsular release for glenohumeral osteoarthritis. AB - Osteoarthritis of the glenohumeral joint in younger, active patients presents a difficult situation to the surgeon, who would like to delay the necessity for hemiarthroplasty or total shoulder replacement until the patient is older and less active. This report outlines our technique of arthroscopic debridement and capsular release. By using electrocautery to release the rotator interval, anterior capsule, posterior capsule, and axillary recess, we have been able to improve the range of motion and to achieve pain relief. In 8 patients the mean improvement in range of motion was as follows: forward elevation, 21.4 degrees ; external rotation, 16.6 degrees; and internal rotation, 31.1 degrees. We believe that a reduction in joint contact pressures through a greater range of motion is the primary mechanism for pain relief resulting from capsular release. PMID- 17868844 TI - Diagnosis and arthroscopic treatment of primary synovial chondromatosis of the shoulder. AB - Primary synovial chondromatosis of the shoulder is a rare condition. We present the case of a 24-year-old man with a 6-month history of right shoulder pain and decreased range of motion. Computed tomography and magnetic resonance imaging findings led us to the diagnosis of synovial chondromatosis of the shoulder. Arthroscopy revealed loose bodies in the glenohumeral joint, the biceps tendon sheath, and the subscapularis recess. Active intrasynovial proliferation of the axillary pouch was noted. All loose bodies were removed arthroscopically, and partial synovectomy was performed. Histologic examination confirmed the diagnosis of primary synovial chondromatosis. We recommend arthroscopic treatment for synovial chondromatosis of the shoulder because of low morbidity and early functional return. PMID- 17868845 TI - Osteochondral grafting for treatment of a massive chondral defect in the knee of a young adult with anterior cruciate ligament deficit. AB - We report the case of a 28-year-old woman who underwent osteochondral grafting and anterior cruciate ligament (ACL) reconstruction for treatment of a massive cartilage defect in a knee joint with ACL deficit. Arthroscopy showed a full thickness degenerative cartilage defect measuring 22 x 35 mm in the weight bearing area of the medial femoral condyle, a totally resected lateral meniscus, and a loosened ACL. Therefore we performed osteochondral autograft transplantation and ACL reconstruction. Osteochondral plugs were harvested from a donor site in the patellofemoral joint of the contralateral knee and grafted into the recipient site in a "skipping" manner. Arthroscopic examination 1 year after surgery showed good preservation of the grafts and satisfactory bridging of the gaps between the plugs with fibrocartilage-like tissue. A recent follow-up examination, performed 36 months after surgery, has shown an excellent result, with a Lysholm score of 100, an International Knee Documentation Committee score of 95.4, and full range of knee motion with no symptoms. Plain radiographs at that time showed preservation of the medial joint space on the weighted anteroposterior view. No osteoarthritic changes were evident in the patellofemoral joint. PMID- 17868846 TI - Posterosuperior osteochondritis of the calcaneus. AB - Osteochondritis of the posterosuperior area of the talocalcaneal surface is a relatively uncommon injury, and only 1 case has been described in the literature. We present a 37-year-old man who complained of pain in the tarsal canal area during walking and when standing up. The magnetic resonance imaging study showed an osteochondral signal in the posterosuperior medial area of the calcaneus on the talocalcaneal surface. The persistence of pain and lack of improvement with conservative treatment made arthroscopic debridement of the injury necessary. The arthroscopic procedure was performed through 2 medial portals, made under fluoroscopy, marked with needles, and dissected with mosquito clamps, and the affected surface could be fully visualized, showing a chondral lesion. Debridement of the osteonecrotic area was performed, and the Steadman technique was used on the injured bone surface. The patient was pain-free, and limited activity (i.e., standing up and walking without symptoms) was allowed. After 24 months, the patient remains asymptomatic with weight-bearing working activities and when standing. Arthroscopic curettage and scission of the injury have been shown to yield good or excellent outcomes in 75% to 80% of patients with regard to the talar surface. PMID- 17868847 TI - Failure of primary ACL surgery using anterior tibialis allograft via transtibial technique. PMID- 17868849 TI - Tensioning in double-bundle ACL reconstruction. PMID- 17868850 TI - The effect of hydrofluoric acid treatment of TiO2 grit blasted titanium implants on adherent osteoblast gene expression in vitro and in vivo. AB - It is widely accepted that implant surface factors affect the quality of the bone to-implant interface. Recent additional treatments superimposed on moderately rough cpTitanium surface provide further enhancement of bone-to-implant contact. The aim of this study was to compare osteoinductive and bone-specific gene expression in cells adherent to titanium dioxide-grit blasted (TiO2) versus TiO2 grit blasted and HF treated (TiO2/HF) cpTitanium implant surfaces. MC3T3-E1 cells were grown in osteogenic supplements on the titanium disk surfaces for 1-14 days. Real-time PCR was used to measure RUNX-2, Osterix, and bone sialoprotein (BSP) mRNA levels. Implants were placed in rat tibia and, following harvesting at 1-7 days after placement, real-time PCR was used to measure RUNX-2, alkaline phosphatase (ALP), and BSP mRNA levels in implant adherent cells. In cell culture, RUNX-2 and Osterix levels were significantly increased (p<0.05) on the TiO2/HF surfaces as compared to the TiO2 and smooth surfaces through the cultural period, while BSP expression was elevated on both TiO2 and TiO2/HF surfaces when compared to a machined surface control. In cells adherent to implants retrieved from rat tibia, RUNX-2 mRNA levels were 2-fold and 8-fold greater on the TiO2/HF surfaces at 1-3 and 7 days following implantation. This was paralleled by significantly greater levels of ALP at 3 and 7 days and BSP mRNA at 7 days following implantation. As a marker of osteoinduction, the increased levels of RUNX-2 in cells adherent to the TiO2/HF surfaces suggest that the additional HF treatment of the TiO2 grit blasted surface results in surface properties that support adherent cell osteoinduction. In vivo assessments of implant adherent cell phenotypes provide further insight into the mechanisms affecting alloplast tissue interactions. PMID- 17868853 TI - Clinical overview of hypereosinophilic syndromes. AB - Hypereosinophilic syndrome (HES) or syndromes are disorders characterized by chronic peripheral blood hypereosinophilia with damage to various organs due toeosinophilic infiltration and release of mediators. HES is most accurately described as a collection of heterogeneous disorders, with some similarities in clinical features, but many differences. Based on recent advances in molecular and genetic diagnostic techniques and increasing experience with differences in clinical features and prognosis, some subtypes of HES have been defined, such as myeloproliferative variants, including chronic eosinophilic leukemia, and lymphocytic variants, but other subtypes remain undefined. Recent evidence suggests that, in addition to differences in clinical features, the range of complications, treatment options, and prognoses differs significantly among the myeloproliferative, lymphocytic, and undefined variants of HES. PMID- 17868855 TI - Chronic eosinophilic leukemias and the myeloproliferative variant of the hypereosinophilic syndrome. AB - Among patients with hypereosinophilia, a myeloproliferative variant is recognized. In many of these patients a diagnosis of eosinophilic leukemia can be made. The molecular mechanism is often a fusion gene, incorporating part of PDGFRA or PDGFRB, encoding anaberrant tyrosine kinase. Prompt diagnosis of such cases is important since specific tyrosine kinase inhibitor therapy is indicated. PMID- 17868856 TI - Lymphocytic variant hypereosinophilic syndromes. AB - A large body of evidence establishing the existence of an underlying T-cell disorder in a subset of patients fulfilling hypereosinophilic syndrome (HES) diagnostic criteria has accumulated over the past decade, resulting in the definition of a novel HES variant termed "lymphocytic" HES. Although end-organ complications of hypereosinophilia are generally benign, with predominant cutaneous manifestations, long-term prognosis is overshadowed by an increased risk of developing T-cell lymphoma, as a result of malignant transformation of aberrant T cells years after HES diagnosis. Therapeutic strategies should target pathogenic T cells in addition to eosinophils, but the practical implications remain largely unexplored. PMID- 17868854 TI - Mechanisms of eosinophilia in the pathogenesis of hypereosinophilic disorders. AB - The increased numbers of activated eosinophils in the blood and tissues that typically accompany hypereosinophilic disorders result from a variety of mechanisms. Exciting advances in translating discoveries achieved from mouse models and molecular strategies to the clinic have led to a flurry of new therapeutics specifically designed to target eosinophil-associated diseases. So far, this form of hypothesis testing in humans in vivo through pharmacology generally has supported the paradigms generated in vitro and in animal models, raising hopes that a spectrum of novel therapies soon may become available to help those who have eosinophil-associated diseases. PMID- 17868857 TI - Dermatologic manifestations of the hypereosinophilic syndromes. AB - Skin is a commonly affected organ in hypereosinophilic syndromes (HES). Cutaneous lesions may be an important presenting sign, may be extremely debilitating, and often reflect disease activity in HES. Recognition of dermatologic manifestations is important in approaching diagnosis and treatment of HES. This article reviews cutaneous involvement in HES and other eosinophil-associated skin diseases. PMID- 17868858 TI - Gastrointestinal eosinophilia. AB - Gastrointestinal eosinophilia, a broad term for abnormal eosinophil accumulation in the gastrointestinal tract, involves many different disease identities. These diseases include primary eosinophil associated gastrointestinal diseases, gastrointestinal eosinophilia in hypereosinophilic syndrome, and all gastrointestinal eosinophilic states associated with known causes. Each of these diseases has its unique features but there is no absolute boundary between them. All three groups of gastrointestinal eosinophila are described in this article, although the focus is on primary gastrointestinal eosinophilia. PMID- 17868860 TI - Pulmonary eosinophilic syndromes. AB - Acute eosinophilic pneumonia, chronic eosinophilia, Churg-Strauss syndrome, and the hypereosinophilic syndrome are pulmonary eosinophilic syndromes characterized by an increased number of eosinophils in peripheral blood, in lung tissue, in sputum, in bronchoalveolar lavage fluid, or in all of these. These pulmonary eosinophilic syndromes generally are characterized by increased respiratory symptoms, abnormal radiographic appearance, and the potential for systemic manifestations. It is critical to exclude other causes of eosinophilia in patients who have lung disease, to make a quick diagnosis, and to treat aggressively with corticosteroids and other therapies to prevent long-term sequelae. PMID- 17868861 TI - Treatment of hypereosinophilic syndromes with prednisone, hydroxyurea, and interferon. AB - The hypereosinophilic syndromes continue to challenge our clinical acumen and skills. Prednisone, hydroxyurea, and interferon alpha 2b are three of the oldest agents that allow control of eosinophilia and its devastating clinical consequences. They still work. As our experience with them has grown, it has become evident that use of these agents in combination will control eosinophilia in most patients. Moreover, with time, the doses can frequently be reduced. Even with the advent of newer agents for treatment of hypereosinophilic syndromes, these three medications still afford an excellent, cost-effective avenue for disease management. PMID- 17868859 TI - Cardiovascular manifestations of hypereosinophilic syndromes. AB - The hypereosinophilic syndromes (HESs) are characterized by persistent marked eosinophilia (>1500 eosinophils/mm(3)), the absence of a primary cause of eosinophilia (such as parasitic or allergic disease), and evidence of eosinophil mediated end organ damage. Cardiovascular complications of HES are a major source of morbidity and mortality in these disorders. The most characteristic cardiovascular abnormality in HES is endomyocardial fibrosis. Patients who have an HES also may develop thrombosis, particularly in the cardiac ventricles, but also occasionally in deep veins. Because of the rarity of these disorders, specific guidelines for the management of the cardiac and thrombotic complications of HES are lacking. This article reviews the diagnosis and management of the cardiovascular manifestations of HES. PMID- 17868862 TI - Novel approaches to therapy of hypereosinophilic syndromes. AB - There has been recent progress in the understanding of the pathogenesis of the hypereosinophilic syndromes (HES). This led to the distinction of subgroups, in which the underlying cause has been identified. Consequently, new treatment options became available, such as imatinib and mepolizumab, which proved to be promising. This article summarizes these new pharmacologic approaches to the therapy of HES. PMID- 17868864 TI - Approach to the therapy of hypereosinophilic syndromes. AB - With the introduction of new diagnostic methods and treatment modalities, it has become increasingly clear that hypereosinophilic syndromes (HES) are a heterogeneous group of disorders for which a single approach to treatment is insufficient. This article discusses current treatment modalities for myeloproliferative HES, idiopathic HES, and lymphocytic-variant HES. PMID- 17868863 TI - Evaluation and differential diagnosis of marked, persistent eosinophilia. AB - Hypereosinophilic syndromes (HES) are a group of heterogeneous disorders many of which remain ill-defined. By definition, the HES must be distinguished from other disorders with persistently elevated eosinophilia with a defined cause. Although marked eosinophilia worldwide is most commonly caused by helminth (worm) infections, the diagnostic approach must include noninfectious (nonparasitic) causes of marked eosinophilia as well. PMID- 17868865 TI - Adverse childhood experiences and childhood autobiographical memory disturbance. AB - OBJECTIVE: To examine relationships between childhood autobiographical memory disturbance (CAMD) and adverse childhood experiences (ACEs) which are defined as common forms of child maltreatment and related traumatic stressors. METHODS: We use the ACE score (an integer count of eight different categories of ACEs) as a measure of cumulative exposure to traumatic stress during childhood. In a cross sectional analysis we assess the relationship of the ACE score to the prevalence of CAMD in a sample of 9,460 relatively healthy adults evaluated for wellness care at a southern California health maintenance organization between August 1995 and March 1996. In addition, we examined possible secular influences by examining association among each of four birth cohorts. Logistic regression was used to obtain the adjusted relative odds of CAMD associated with increasing ACE score. RESULTS: Overall, the age-standardized prevalence of CAMD was 18% (men: 15%; women: 19%). As the ACE score increased, the prevalence of CAMD increased in a graded fashion for both men and women (p for trend <.0001). After adjustment for age, sex, race/ethnicity, and education, adults with an ACE score >or=6 were 5.9 (95% CI, 4.4-7.9) times more likely to have CAMD compared to adults with an ACE score of 0. The prevalence of CAMD increased with each successive birth cohort, and graded relationships between the ACE score and CAMD were observed among each of the four birth cohorts though no statistical difference in the association was found across birth cohorts. CONCLUSIONS: The accumulation of ACEs across several domains is associated CAMD among men and women and in each of four birth cohorts. Further research is needed that describes the prevalence of CAMD in population based samples and that examines whether impaired memory is a marker for persons neurobiologically affected by multiple forms of child maltreatment and related traumatic stressors. PMID- 17868866 TI - Multiple alpha subunits of integrin are involved in cell-mediated responses of the Manduca immune system. AB - The cell-mediated responses of the insect innate immune system-phagocytosis, nodulation, encapsulation-involve multiple cell adhesion molecules of hemocyte surfaces. A hemocyte-specific (HS) integrin and a member of the immunoglobulin (Ig) superfamily (neuroglian) are involved in the encapsulation response of hemocytes in Manduca sexta. In addition, two new integrin alpha (alpha) subunits have been found on these hemocytes. The alpha2 subunit is mainly expressed in epidermis and Malphigian tubules, whereas the alpha3 subunit is primarily expressed on hemocytes and fat body cells. Of the three known alpha subunits, the alpha1 subunit found in HS integrin is the predominant subunit of hemocytes. Cell adhesion assays indicate that alpha2 belongs to the integrin family with RGD binding motifs, confirming the phylogenetic analysis of alpha subunits based on the amino-acid sequence alignment of different alpha subunits. Double-stranded RNAs (dsRNAs) targeting each of these three integrin alpha subunits not only specifically decreased transcript expression of each alpha subunit in hemocytes, but also abolished the cell-mediated encapsulation response of hemocytes to foreign surfaces. The individual alpha subunits of M. sexta integrins, like their integrin counterparts in mammalian immune systems, have critical, individual roles in cell-substrate and cell-cell interactions during immune responses. PMID- 17868867 TI - A review of medial temporal lobe and caudate contributions to visual category learning. AB - Here we review recent functional neuroimaging, neuropsychological and behavioral studies examining the role of the medial temporal lobe (MTL) and the caudate in learning visual categories either by verbalizeable rules or without awareness. The MTL and caudate are found to play dissociable roles in different types of category learning with successful rule-based (RB) categorization depending selectively on the MTL and non-verbalizeable information-integration (II) category learning depending on the posterior caudate. These studies utilize a combination of experimental cognitive psychology, mathematical modeling (Decision Bound Theory (DBT)) and cognitive computational modeling (the COVIS model of Ashby et al. [1998. A neuropsychological theory of multiple systems in category learning. Psychological Review 105, 442-481]) to enhance the understanding of data obtained via functional magnetic resonance imaging (fMRI). The combination of approaches is used to both test hypotheses of the cognitive model and also to incorporate hypotheses about the strategies used by participants to direct analysis of fMRI data. Examination of the roles of the MTL and caudate in visual category learning holds the promise of bridging between abstract cognitive models of behavior, systems neuroscience, neuropsychology, and the underlying neurophysiology of these brain regions. PMID- 17868868 TI - Critical linkages between land-use transition and human health in the Himalayan region. AB - This article reviews critical linkages between land-use transition and human health in the Himalayan region by applying ecosystem approaches to human health (or EcoHealth). Land-use transition in the Himalayan and similar regions includes sedentarization, agricultural intensification, habitat modification, migration, change of livelihoods and lifestyles, biodiversity loss, and increasing flash floods. These transitions, which can have impacts on human health, are driven by state policies, a market economy, and climate change. Human health is dependent on access to ecosystem services for food, nutrition, medicine, fiber and shelter, fresh water, and clear air. Ecosystem management has been a key means of controlling disease vectors and creating suitable habitats for human well-being. The paper identifies the web of environmental factors that influence human health. Institutional and policy issues for land-use and health transitions are also discussed. PMID- 17868869 TI - Reduced exposure to air pollution on the boardwalk in Dublin, Ireland. Measurement and prediction. AB - This paper outlines an air pollution study carried out on Dublin city's recently completed boardwalk along the side of and overhanging the River Liffey. Air quality samples were taken along the length of the boardwalk to investigate whether pedestrians using the boardwalk would have a lower air pollution exposure than those using the adjoining footpath along the road. The results of the study show significant reductions in pedestrian exposure to both traffic derived particulates and hydrocarbons along the boardwalk as opposed to the footpath. Computational fluid dynamics was also used to model the outcome of these field measurements and shows the importance of the boundary wall between the footpath and boardwalk in reducing air pollution exposure for the pedestrian, the results of which are also presented herein. PMID- 17868870 TI - The Cbl-b RING finger domain has a limited role in regulating inflammatory cytokine production by IgE-activated mast cells. AB - The RING finger type E3 ubiquitin ligase, Cbl-b, is abundantly expressed in bone marrow-derived mast cells (BMMCs) and functions as a potent negative regulator of signalling responses from the high-affinity IgE receptor (FcvarepsilonRI). To determine the contribution of Cbl-b E3 ligase activity we generated knockin mice with a loss-of-function mutation in the RING finger domain. We find the mice to be healthy and, unlike equivalent c-Cbl RING finger mutant mice, produce homozygous offspring at the expected frequency. Comparative analyses of BMMCs from Cbl-b knockout and Cbl-b RING finger mutant mice revealed that both showed similarly enhanced FcvarepsilonRI signalling compared to wild-type cells for most parameters examined. A notable exception was a markedly higher level of activation of IkappaB kinase (IKK) in Cbl-b knockout BMMC compared to RING finger mutant-derived cells. In addition BMMCs from the Cbl-b RING finger mutant did not retard FcvarepsilonRI internalization to the extent observed for knockout cells. Most striking however was the finding that RING finger mutant mast cells do not produce the very high levels of TNF-alpha, IL-6, and MCP-1 evident in Cbl-b knockout cultures following FcvarepsilonRI activation. Thus the ability of Cbl-b to function as a negative regulator of FcvarepsilonRI signalling that promotes inflammatory cytokine production is largely independent of the RING finger domain. PMID- 17868871 TI - Functional analysis of the host defense peptide Human Beta Defensin-1: new insight into its potential role in cancer. AB - Although it is known that innate immunity is key for protecting the body against foreign agents such as bacteria, little is known about elements of the innate immune system that have anti-tumor activity. Human Beta Defensin-1 (hBD-1), an important component of the innate immune response, is lost at high frequencies in malignant prostatic tissue, while high levels of expression are maintained in adjacent benign regions. In prostate carcinoma, frequent genetic alterations occur in the 8p22-23 region and several studies indicate there may be multiple tumor suppressor genes present within this region. The high incidence of loss of hBD-1 expression in prostate cancer, along with its chromosomal location of 8p23.2, raised the possibility that it may play a role in tumor suppression. To gain insight as to its function in prostate cancer, hBD-1 was cloned and ectopically expressed in four prostate cancer cell lines. Induction of hBD-1 expression resulted in a decrease in cellular growth in DU145 and PC3 cells. However, hBD-1 has no effect on the growth of androgen receptor (AR) positive LNCaP prostate cancer cells, but was again growth suppressive to PC3 cells with ectopic AR expression (PC3/AR+). hBD-1 also caused rapid induction of cytolysis and caspase-mediated apoptosis in DU145 and PC3 prostate cancer cells. Although the regulation of hBD-1 was not addressed in this study, our preliminary data demonstrated that the pathways involved may include cMYC and PAX2. Data presented here are the first to provide evidence of its potential role in prostate cancer cell death. PMID- 17868872 TI - PD-1 upregulation is associated with HBV-specific T cell dysfunction in chronic hepatitis B patients. AB - Programmed death-1 (PD-1) is demonstrated to have an increased expression on antigen-specific T cells during chronic virus infections, and the blockage of PD 1/PD-ligand (PD-L1) pathway could restore the function of exhausted T cells. We measured the PD-1 expression levels on HBV-specific CD8 T cells and investigated the role of PD-1/PD-L1 pathway in T-cell responses of patients with different HBV infection statuses. Compared to the patients with convalescent acute hepatitis B, PD-1 expression on total CD8 T cells from chronic hepatitis B (CHB) patients was significantly upregulated, especially on the HBV pentamer-positive CD8 T cells. And PD-L1, but not PD-L2, was also significantly upregulated on PBMC from CHB patients. In CHB patients, HBV-specific T cells and cellular proliferation could be observed under the recombinant HBV-Ag stimulation in vitro, and blockade of PD 1 pathway significantly enhanced the IFN-gamma production and cellular proliferation of PBMC. Furthermore, PD-1 expression level on HBV-pentamers positive CD8 T cells was positively associated with plasma viral load in CHB patients. Thus, PD-1 upregulation on HBV-specific CD8 T cells is engaged in the dysfunction of T cells and high viraemia in CHB patients, and the antiviral T cell responses could be improved by the blockade of this inhibitory PD-1/PD-L1 pathway. PMID- 17868873 TI - Endothelial cell loss after descemet stripping with endothelial keratoplasty influencing factors and 2-year trend. AB - PURPOSE: To identify factors correlated with early endothelial cell loss after Descemet stripping with endothelial keratoplasty (DSEK) and to document cell loss over a 2-year period. DESIGN: Cross-sectional and longitudinal retrospective analyses. PARTICIPANTS: A series of 263 eyes in 216 patients who were treated with DSEK and were examined at the same center after surgery. METHODS: Six-month endothelial cell density (ECD) measurements were analyzed by multivariate analysis of variance to identify preoperative, operative, and postoperative factors that significantly influenced early cell loss. In addition, ECD measurements were compared longitudinally at 6, 12, and 24 months after grafting. MAIN OUTCOME MEASURES: Central ECD after transplantation. RESULTS: Mean ECD was 2000+/-550 cells/mm(2) 6 months after DSEK, representing cell loss of 34+/-18%. Factors associated with lower 6-month cell loss were use of single-point fixation forceps that compressed the donor tissue only at the tip during graft insertion (P = 0.025) and absence of any secondary donor reattachment procedure (P = 0.035). Six-month cell loss also was significantly less when DSEK was performed as a combined procedure; in combined cases, the graft was inserted through a clear corneal incision, whereas in standard cases, it was inserted through a scleral tunnel incision, which likely exerted more compression. Cell loss was comparable with manual and microkeratome donor dissection techniques (P = 0.91). Postoperative ECD was correlated positively with donor ECD (P<0.0001) and was correlated inversely with donor age (P<0.0001), although these donor characteristics explained only 10% of the total variance in 6-month ECD. Factors not significantly correlated with 6-month ECD or cell loss included donor death to-preservation time (range, 1-22 hours; P = 0.45), donor death-to-use time (range, 2-8 days; P = 0.86), and recipient demographics. In 34 DSEK eyes analyzed longitudinally, mean ECD was 3100+/-250 cells/mm(2) before surgery, 2000+/-540 cells/mm(2) at 6 months, 1900+/-480 cells/mm(2) at 1 year, and 1800+/-490 cells/mm(2) at 2 years. CONCLUSIONS: Cell loss 6 months and 1 year after DSEK was higher than in a recent penetrating keratoplasty series performed at the same center, consistent with more donor tissue manipulation in DSEK. Cell loss was reduced with certain variations in surgical technique. PMID- 17868874 TI - Macular pigment density and age-related maculopathy in the Carotenoids in Age Related Eye Disease Study. An ancillary study of the women's health initiative. AB - PURPOSE: To examine the association between intermediate age-related macular degeneration (AMD) and the optical density of macular pigment (MPOD), which is composed of lutein and zeaxanthin from the diet. DESIGN: Cross-sectional cohort study. PARTICIPANTS: We included 1698 of 2005 women ages 54 to 86 years and participating in the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women's Health Initiative. METHODS: The MPOD was measured noninvasively by heterochromatic flicker photometry. Fundus photographs were taken to document prevalent AMD. MAIN OUTCOME MEASURES: Intermediate AMD (n = 305) and two subtypes-large drusen (n = 233) and pigmentary abnormalities (n = 157). RESULTS: After adjusting for covariates, the odds ratio (OR) and 95% confidence interval (CI) for AMD among women in quintile (Q) 5 (n = 339) versus 1 (n = 340) for MPOD was 1.4 (0.9, 2.1). However, after excluding women with possible unstable diets and recent supplement use due to chronic disease history, associations reversed (OR Q2-5 vs. 1, 0.8; 95% CI, 0.5-1.2), but remained nonsignificant. Associations also differed between middle-aged (54-69 years) and older (> or =70 years) women (P-interaction = 0.09), but less so, after excluding women who were likely to have unstable diets: adjusted ORs (95% CI) were 0.5 (0.3 1.0; P = 0.08) for intermediate AMD among middle-aged women (n = 516) with MPOD in Q2 to Q5 versus 1 and 1.0 (0.5-2.0; P = 0.90) for older women (n = 422). CONCLUSIONS: The MPOD is not cross-sectionally associated with AMD. The inconsistency of relationships across age groups and in subgroups of women who are likely to have more stable diets suggests that cross-sectional associations may be biased and highlights the need to study these relationships prospectively. PMID- 17868875 TI - Achilles' heel of stentless porcine valves. PMID- 17868876 TI - Inflammation and infection in nine surgically explanted Medtronic Freestyle stentless aortic valves. AB - BACKGROUND: The Medtronic Freestyle valve is fixed in glutaraldehyde at zero pressure on the cusps and treated with alpha-amino oleic acid. This valve reportedly has excellent clinical and hemodynamic results, but little has been reported about its long-term pathology. METHODS AND RESULTS: Nine Freestyle valves explanted between 2003 and 2005 were reviewed to assess the reasons for bioprosthesis failure (six implanted at our institution). All valves were examined in detail, using histochemistry and immunohistochemistry to identify the cellular response. One Freestyle valve, explanted for mitral valve endocarditis on the fifth postoperative day, was excluded from analysis. Average implant duration was 52.8+/-35.5 months. Four valves were explanted for infective endocarditis, three for aortic insufficiency, two for aortic stenosis with cusp calcification seen in five valves, pannus and thrombus in all valves and a chronic inflammatory reaction involving the xenograft arterial wall seen in eight of nine valves. This was associated with significant damage to the porcine aortic wall in seven cases, and cusp myocardial shelf damage in six cases. CONCLUSIONS: In this series of valves, we found (1) infective endocarditis; (2) pannus, thrombus, and calcification; and (3) unusual and significant inflammatory reaction and aortic tissue damage, which could by itself lead to aortic incompetence. PMID- 17868877 TI - Synergistic effects of cyclic tension and transforming growth factor-beta1 on the aortic valve myofibroblast. AB - BACKGROUND: Phenotypically, aortic valve interstitial cells are dynamic myofibroblasts, appearing contractile and activated in times of development, disease, and remodeling. The precise mechanism of phenotypic modulation is unclear, but it is speculated that both biomechanical and biochemical factors are influential. Therefore, we hypothesized that isolated and combined treatments of cyclic tension and transforming growth factor-beta1 would alter the phenotype and subsequent collagen biosynthesis of aortic valve interstitial cells in situ. METHODS AND RESULTS: Porcine aortic valve leaflets received 7- and 14-day treatments of 15% cyclic stretch (Tension); 0.5 ng/ml transforming growth factor beta1 (TGF); 15% cyclic stretch and 0.5 ng/ml transforming growth factor-beta1 (Tension+TGF); or neither mechanical nor cytokine stimuli (Null). Tissues were homogenized and assayed for aortic valve interstitial cell phenotype (smooth muscle alpha-actin) and collagen biosynthesis (via heat shock protein 47, which was further verified with type I collagen C-terminal propeptide). At both 7 and 14 days, smooth muscle alpha-actin, heat shock protein 47, and type I collagen C terminal propeptide quantities were significantly greater (P<.001) in the Tension+TGF group than in all other groups. Additionally, Tension alone appeared to maintain smooth muscle alpha-actin and heat shock protein 47 levels that were measured on Day 0, while TGF alone elicited an increase in smooth muscle alpha actin and heat shock protein 47 compared to Day 0 levels. Null treatment revealed diminished proteins at both time points. CONCLUSIONS: Elevated transforming growth factor-beta1 levels, in the presence of cyclic mechanical tension, resulted in synergistic increases in contractile and biosynthetic proteins in aortic valve interstitial cells. Since cyclic mechanical stimuli can never be relieved in vivo, the presence of transforming growth factor-beta1 (possibly from infiltrating macrophages) may result in overly biosynthetic aortic valve interstitial cells, leading to altered extracellular matrix architecture, compromised valve function, and, ultimately, degenerative valvular disease. PMID- 17868878 TI - Healing and remodeling of bioengineered pulmonary artery patches implanted in sheep. AB - PURPOSE: We hypothesized that cell-seeded patches implanted into sheep pulmonary artery would undergo progressive and complete healing into a viable structure well integrated with the arterial wall. METHODS: Autologous ovine blood-derived endothelial progenitor cells (EPCs) and bone marrow-derived mesenchymal stem cells (MSCs) were isolated and cultured in vitro. MSCs and EPCs were seeded onto poly-4-hydroxybutyrate (P4HB)-coated polyglycolic acid (PGA) nonwoven biodegradable mesh scaffolds (10x20 mm) and cultured for 5 days in a laminar fluid flow system. Seeded patches were implanted into the wall of sheep pulmonary artery for 1-2 weeks (n=4) or 4-6 weeks (n=3). Preimplant and postexplant specimens were analyzed by histology and immunohistochemistry. RESULTS: Unimplanted constructs contained alpha-smooth muscle actin (SMA)-positive cells and early extracellular matrix formation (primarily glycosaminoglycans). One week after implantation, seeded patches had surface thrombus formation and macrophage infiltration. Seeded patches implanted for 2 weeks showed granulation tissue, early pannus formation, macrophages, foreign body giant cells around disintegrating polymer, and early angiogenesis (microvessel formation). After 4 weeks in vivo, seeded patches contained glycosaminoglycans, collagen, and coverage of the luminal surface by host artery-derived pannus containing alpha SMA-positive cells and laminated elastin; polymer scaffold degradation was almost complete with replacement by fibrous tissue containing viable cells. CONCLUSIONS: This study shows that cell-seeded patches implanted in sheep pulmonary artery remodel to layered and viable tissue well integrated into the native arterial wall. The key remodeling processes included (1) intimal overgrowth at the luminal surface (pannus formation; neointima) and (2) granulation tissue formation and fibrosis with foreign body reaction. PMID- 17868879 TI - Blockade of integrin beta3-FAK signaling pathway activated by osteopontin inhibits neointimal formation after balloon injury. AB - BACKGROUND: Osteopontin (OPN) promotes the migration and adhesion of vascular smooth muscle cells (VSMCs) through cell surface receptor, integrin beta3. In order to elucidate the signaling pathway by which OPN is involved in neointimal formation, we focused on integrin beta3-focal adhesion kinase (FAK) upon VSMC migration. METHODS: The integrin beta3 and FAK expression in VSMC and in neointima was detected by Western blot and immunohistochemistry staining. FAK phosphorylation induced by OPN was verified using a linear OPN 13 peptide containing RGD motif and anti-OPN antibody. The role of integrin beta3-FAK pathway in VSMC adhesion and migration induced with OPN was tested by the overexpression of FAK-related nonkinase and integrin beta3 cytoplasmic domain. RESULTS: The results showed that OPN increased integrin beta3 expression and induced rapid and transient FAK phosphorylation. Inhibition of the phosphorylation of FAK significantly suppressed VSMC migration induced by OPN. Similarly, blockade of the interaction of integrin beta3 with OPN inhibited VSMC adhesion induced by OPN. The experiment, in vivo, demonstrated that OPN expression level was consistent with neointimal thickening. Administration of anti-OPN antibody for blocking OPN function suppressed integrin beta3 and FAK expression induced by balloon injury, and neointimal thickening was inhibited. CONCLUSIONS: These data indicate that integrin beta3-FAK signaling modulates OPN induced VSMC migration during neointimal formation. PMID- 17868880 TI - Expression of vascular endothelial growth factor and receptor tyrosine kinases in cardiac ischemia/reperfusion injury. AB - INTRODUCTION: Vascular endothelial growth factor (VEGF) expression is regulated by hypoxia and cytokines, including insulin-like growth factor (IGF)-1. We examined the influence of ischemia/reperfusion (I/R) on IGF-1, VEGF, fetal liver kinase (flk-1), fms-like tyrosine kinase-1 (flt-1), and laminin using an isolated hemoperfused working porcine heart model of acute ischemia (2 h) and reperfusion (4 h). METHODS: Twenty-three porcine hearts were randomized into the following groups: five nonischemic control hearts (Group C), five I/R hearts with occlusion of the ramus circumflexus; three I/R hearts treated with quinaprilat, a potent angiotensin-converting enzyme (ACE) inhibitor (Group Q); five I/R hearts treated with angiotensin I (Group Ang I), and 5 I/R hearts treated with Ang I and quinaprilat (Group QA). RESULTS: Compared to C, VEGF mRNA and protein contents were significantly increased in I/R and Ang I hearts. flk-1 and flt-1 were increased in I/R (2.2-/1.95-fold) and further elevated by Ang I (3.2-/3.4-fold) compared with C. Quinaprilat application attenuated the amount of VEGF significantly and of flk-1 slightly but not that of flt-1. In contrast, IGF-1 and IGF-1 receptor (IGF-1R) proteins were elevated in I/R hearts (3-/1.4-fold vs. C) and further increased in the presence of Q. These findings were accompanied by an elevation of laminin mRNA and protein levels. Moreover, we observed an increase in collagen Type IV and chondroitin sulfate content in I/R (2.9-/1.4-fold) and Ang I (3.5-/1.5-fold) hearts. Quinaprilat significantly reduced laminin and chondroitin sulfate proteins. CONCLUSION: These data suggest that the VEGF/VEGF receptor and IGF-1-IGF-1R systems are activated by I/R. The benefits of ACE inhibition in attenuation of cardiac remodeling may be mediated by IGF-1. PMID- 17868881 TI - Expression of cyclooxygenase-1 and cyclooxygenase-2 in the normal human heart and in myocardial infarction. AB - INTRODUCTION: Cyclooxygenase is a key enzyme in prostanoid synthesis. It exists in two isoforms: cyclooxygenase-1 (COX-1), which is constitutively expressed in cells and tissues maintaining normal homeostasis, and cyclooxygenase-2 (COX-2), which is normally not present in most cells, but can be induced by various stimuli. Little is known about the significance of COX isoforms in the normal human heart and in myocardial infarction (MI). Thus, we aimed to investigate the immunohistochemical expression of COX-1 and COX-2 in the normal human heart and in MI. METHODS: Our study included autopsy samples of heart tissue from 15 healthy individuals who died in accidents, and from 40 patients with MI who died few hours to a month after the onset of symptoms. Immunohistochemistry was performed by a sensitive peroxidase-streptavidin method on formalin fixed, paraffin-embedded tissue, using monoclonal antibodies against COX-1 and COX-2. RESULTS: In normal hearts, COX-1 was found in endothelial and smooth muscle cells of blood vessels and in endothelial cells of the endocardium. In MI, it was expressed in inflammatory cells, as well as in myofibroblasts and capillaries of granulation and fibrous tissue. COX-2 was either not present or it was present in occasional myocytes in the normal hearts. In MI, its expression was induced in cardiomyocytes as well as in interstitial inflammatory cells, and in capillaries and myofibroblasts in granulation tissue. CONCLUSIONS: Our results suggest that COX-1 is associated with normal homeostasis in the heart, whereas COX-2 probably mediates inflammatory reaction in MI. It appears that both COX-1 and COX-2 are associated with the healing processes and scar formation after MI. PMID- 17868882 TI - Folic acid reduces chemokine MCP-1 release and expression in rats with hyperhomocystinemia. AB - OBJECTIVE: This study aimed to investigate the effects of folate on the monocyte chemoattractant protein-1 (MCP-1) expression and release in rats with hyperhomocystinemia induced by ingestion of excess methionine. METHODS AND RESULTS: Thirty male Sprague-Dawley rats (200+/-20 g) were randomly divided into three groups (n=10 for each group): control group (Control), high-homocystinemia (Hhcy) group, and folate treatment (FA) group. They were fed with a normal regular diet, enriched by 1.7% methionine plus 1.7% methionine and 0.006% folate for 45 days. Our study showed the following: (a) A high methionine diet for 45 days is sufficient to induce hyperhomocystinemia; folate supplementation to the rats fed the high-methionine diet prevented an elevation homocysteine (Hcy) levels in the blood (P<.01). (b) Compared with the Control group, the Hhcy group had elevated plasma levels of MCP-1, and Hcy was significantly correlated with MCP-1 (P<.05). (c) The protein and mRNA expression of MCP-1 in the aorta was higher in rats from the Hhcy group than in rats from the Control group. (d) Most important, after folic acid supplementation, the lowering of Hcy levels was accompanied by a marked reduction of MCP-1 expressed in aortae and released from plasma and peripheral blood mononuclear cells (PBMCs) stimulated by oxidized low density lipoprotein (P<.05, P<.01). CONCLUSION: Folic acid supplementation not only can blunt the rise in Hcy and reduce MCP-1 released from both plasma and PBMCs of rats with hyperhomocystinemia but also can downgrade MCP-1 expression in the aorta of rats with hyperhomocystinemia. PMID- 17868883 TI - Left ventricular hypertrabeculation (noncompaction) with prominent calcifications in a patient with mannose-binding lectin deficiency and unclassified myopathy. AB - OBJECTIVES: The aim of this study was to report the histological findings of a patient with left ventricular hypertrabeculation (LVHT, noncompaction), mannose binding lectin (MBL) deficiency, and unclassified myopathy in whom also endocardial thickening and calcifications over the compacted and noncompacted layer were found. CASE REPORT: In a 47-year-old man with left bundle-branch block, ventricular runs, and dilative cardiomyopathy with systolic dysfunction since childhood, LVHT was detected at 40 years of age. At the same time, intracardial calcifications were recognized on a thoracic computed tomographic scan. MBL deficiency was identified as the cause of recurrent respiratory infections since childhood at 45 years of age. Easy fatigability, myalgias, ptosis, and warming-up phenomenon were attributed to an unclassified myopathy at 44 years of age. After death from a sepsis with Staphylococcus aureus, autopsy confirmed LVHT and additionally revealed endocardial thickening, endocardial fibrosis, foci of calcifications within the endocardium, and accumulations of degenerated cardiomyocytes within the calcifications. Endocardial fibrosis and calcifications were located over the compacted as well as noncompacted segments. They were attributed to LVHT rather than the MBL deficiency-triggered infections or the preterminal sepsis. CONCLUSIONS: LVHT may be associated with MBL deficiency, unclassified myopathy, and endocardial fibrosis with calcifications over the compacted and noncompacted layer. Endocardial fibrosis with prominent calcifications seems to be a rare manifestation of LVHT. PMID- 17868884 TI - Fibromuscular dysplasia in association with intrauterine cocaine exposure. AB - BACKGROUND: Fibromuscular dysplasia (FMD) is an idiopathic disease of small- and medium-sized arteries, involving one or more vascular beds. Patients may present with a range of symptoms, which may not readily lead to a diagnosis of FMD. While maternal cocaine abuse during pregnancy has previously been associated with vascular alterations in the fetus, an association specifically with FMD has not previously been described. METHODS/RESULTS: In this case report, a 21-month-old male presented with a 3-week history of daily vomiting, with temporary improvement of symptoms, then relapse followed by loss of consciousness. His medical history was significant only for maternal cocaine use. Clinical evaluation revealed dilated cardiomyopathy, and a presumptive diagnosis of myocarditis was rendered. Respiratory arrest and death occurred 2 days after admission. Postmortem examination demonstrated intimal-type multivessel FMD, which was determined to be the cause of the clinical presentation. CONCLUSION: Without a postmortem examination, it is unlikely that a diagnosis of intimal fibroplasia, a rare variant of FMD (5% of cases), would have been made. This case thus illustrates the continuing utility of the classic postmortem examination. More intriguingly, the case suggests a possible relationship between in utero cocaine exposure and the development of fibromuscular dysplasia in the child. PMID- 17868885 TI - Cardiac papillary fibroelastoma in left ventricular apex. AB - Papillary fibroelastoma (PF) is a rare benign heart tumor and represents less than 10% of primary cardiac tumors. It mainly affects the cardiac valves and is often discovered during open heart surgery or autopsy. We present a case of a patient who was detected with a left ventricular apex tumor during the evaluation of the transient ischemic attack. The patient underwent surgery, and subsequently, macroscopic and microscopic examination confirmed the diagnosis of PF. PMID- 17868886 TI - Transcriptional profiling of whole blood and serum protein analysis of mice exposed to the neurotoxin Pacific Ciguatoxin-1. AB - Ciguatoxins (CTX) are a suite of cyclic polyether toxins produced by the marine dinoflagellate Gambierdiscus sp., are potent activators of voltage-gated sodium channels and a leading cause of human poisoning from food fish. This report characterizes the genomic and proteomic response in whole blood of adult male mice exposed i.p. to 264 ng/kg of the Pacific congener of CTX (P-CTX-1) at 1, 4 and 24h. Whole genome microarray expression data were filtered by tightness of fit between replicates, fold change (1.8) and p-value (10(-5)), resulting in 183 annotated genes used for trending analysis, K-means clustering and ontology classification. Genes involved with cytokine signaling, proteasome complex and ribosomal function were dominant. qPCR performed on 19 genes of interest had a correlation of 0.95 to array results by Pearson's correlation coefficient. Serum protein analysis showed small but significant changes in 6 of 60 proteins assayed: Ccl2, Ccl12, CD40, IL-10, leptin and M-CSF. In large part, the gene expression was consistent with a Th2 immune response with interesting similarities to expression seen in asthmatic models. PMID- 17868888 TI - The kinetics and mechanisms of the reactions of iron(III) with quercetin and morin. AB - The kinetics and mechanisms of the reactions of a pseudo-first order excess of iron(III) with the flavonoids quercetin and morin have been investigated in aqueous solution at 25 degrees C and an ionic strength of 0.5M. Mechanisms have been proposed which account satisfactorily for the kinetic data. The data are consistent with a mechanism in which the metal:ligand complex formed initially on reaction of iron(III) with the ligand subsequently decomposes through an electron transfer step. Morin forms a 1:1 metal:ligand complex while quercetin forms a 2:1 metal:ligand complex. Both ligands showed evidence for the involvement of the iron hydroxo dimer Fe2(OH)2(4+) in the complex formation reaction at the hydroxy carbonyl moiety. The iron(III) assisted decomposition of the initial iron(III) complex formed was also investigated and the rate constants evaluated. Both the complex formation and subsequent electron transfer reactions of iron(III) with these ligands were monitored using UV-visible spectrophotometry. All of the suggested mechanisms and calculated rate constants are supported by calculations carried out using global analysis of time dependant spectra. PMID- 17868887 TI - Neuropsychological function in children with blood lead levels <10 microg/dL. AB - Clear adverse effects of blood lead levels >or=10 microg/dL have been documented in children. Given that the majority of US children have levels below 10 microg/dL, clarification of adverse effects below this cutoff value is needed. Our study evaluated the associations between blood lead levels <10 microg/dL and a broad spectrum of children's cognitive abilities. Data were analyzed from 534 children aged 6-10, enrolled in the New England Children's Amalgam Trial (NECAT) from the urban area of Boston, Massachusetts and rural Farmington, Maine. Adjusting for covariates (age, race, socioeconomic status, and primary caregiver IQ), children with 5-10 microg/dL had 5.0 (S.D. 2.3) points lower IQ scores compared to children with blood lead levels of 1-2 microg/dL (p=0.03). Verbal IQ was more negatively affected than performance IQ, with the most prominent decrement occurring in children's vocabulary. Wechsler Individual Achievement Test scores were strongly negatively associated with blood lead levels of 5-10 microg/dL. In adjusted analyses, children with levels of 5-10 microg/dL scored 7.8 (S.D. 2.4) and 6.9 (S.D. 2.2) points lower on reading and math composite scores, respectively, compared to children with levels of 1-2 microg/dL (p<0.01). Finally, levels of 5-10 microg/dL were associated with decreased attention and working memory. Other than associations of lead exposure with achievement, which even persisted after adjustment for child IQ, the most pronounced deficits were in the areas of spatial attention and executive function. Overall, our analyses support prior research that children's blood levels <10 microg/dL are related to compromised cognition and highlight that these may especially be related to academic achievement. PMID- 17868889 TI - Cytotoxic effect, differentiation, inhibition of growth and theoretical calculations of an N,N-donor ligands and its platinum(II), palladium(II) and copper(II) complexes. AB - The new pyrazole ligand 5-(2-hydroxyphenyl)-3-methyl-1-(2-pyridylo)-1H-pyrazole-4 carboxylic acid methyl ester (2) and the corresponding Pt(II), Pd(II) and Cu(II) complexes 3-5 have been synthesized as potential anticancer compounds, and characterized using IR, and (1)H NMR as well as mass spectrometry. The 3-D structures of the Cu(II) complexes were determined by quantum mechanic calculation DFT methodology (density functional theory). The cytotoxicity assay of the ligand and complexes has been performed on leukemia cell lines. In general, the complexes showed lower cytotoxicity than cisplatin, and the Pt(II) and Cu(II) complexes were found to be more efficient in the induction of leukemia cell death than the Pd(II) complex. Our investigations indicate that the antiproliferating activity of the Pt(II) and Cu(II) complexes was partly due to the modulation of cellular differentiation. PMID- 17868890 TI - Marine amphiphilic siderophores: marinobactin structure, uptake, and microbial partitioning. AB - Marinobactins A-E are a suite of amphiphilic siderophores which have a common peptidic head group that coordinates Fe(III), and a fatty acid which varies in length and saturation. As a result of the amphiphilic properties of these siderophores it is difficult to study siderophore-mediated uptake of iron, because the amphiphilic siderophores partition indiscriminately in microbial and other membranes. An alternative method to distinguish amphiphilic siderophore partitioning versus siderophore-mediated active uptake for Fe(III)-marinobactin E has been developed. In addition, a new member of the marinobactin family of siderophores is also reported, marinobactin F, which has a C(18) fatty acid with one double bond and which is substantially more hydrophobic that marinobactins A E. PMID- 17868891 TI - Cervical intraepithelial neoplasia--a new and refreshing approach. PMID- 17868892 TI - Management of cervical intraepithelial neoplasia 2 in adolescent and young women. AB - STUDY OBJECTIVE: To evaluate regression rates among adolescents (aged < or =21) with cervical intraepithelial neoplasia (CIN) 2 managed expectantly and to determine factors associated with disease regression. DESIGN: Cohort study using a colposcopic database of 2,996 women seen between August 1999 and November 2005. SETTING: Colposcopy clinic in urban, tertiary care medical center. PARTICIPANTS: Adolescents with CIN 2. Routine management consisted of two options: immediate treatment or repeat colposcopic evaluation in 6 months. MAIN OUTCOME MEASURES: For those managed conservatively, regression was defined either as a subsequent normal colposcopy and/or biopsy and at least 2 smears read as negative for epithelial abnormality or at least 3 consecutive negative smears if repeat colposcopy was not performed. Demographic information, including age, was assessed to determine possible associations with disease regression. RESULTS: Of the 93 adolescents, 53 (57%) elected to undergo immediate treatment with a diagnostic excisional procedure, and 40 (43%) chose management with colposcopic follow-up. Of those treated, high-grade disease (CIN 2+) was found in 40 (75%). Of the 36 young women followed conservatively (4 were lost to follow-up), regression after a median follow-up time of 378 days was documented in 14 (39%). Of the 22 adolescents not fulfilling our criteria for regression, only 3 had evidence of CIN 2 or worse during follow-up. The remaining 19 had either CIN 1 or mildly abnormal cytologic results. Kaplan-Meier survival estimates indicated younger age (< or =16 years) tended to be associated with decreased time to regression. CONCLUSION: Based on significant regression of CIN 2 among adolescent women, primary management in this population should consist of cytologic and colposcopic follow-up. PMID- 17868893 TI - Interval to treatment of sexually transmitted infections in adolescent females. AB - STUDY OBJECTIVE: To describe (1) the treatment interval for adolescent females with Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC), or Trichomonas vaginalis (TV); (2) the proportion treated in < or =7 days; and (3) factors influencing the treatment interval. DESIGN AND PARTICIPANTS: Charts of sexually active females from an urban teen health center who participated in a larger study and were positive for CT, GC or TV (N = 58) were retrospectively reviewed for dates of treatment, and compared to demographic and symptom data. The treatment interval was defined as days from visit to treatment. CT and/or GC were analyzed together (CT/GC) because presumptive treatment covered both infections, and the diagnostic test (nucleic acid amplification) differed from that of TV (wet mount or culture). RESULTS: The median treatment interval was 0 days for TV, 5 days for CT/GC, and 3 days for any STI. Overall, 39 (69%) were treated within 7 days of their visit. Those with TV were more likely than those with CT/GC to receive treatment at their initial visit (58% vs. 6%). Genitourinary symptoms increased the odds of treatment in < or =7 days. The treatment interval was significantly shorter for subjects who had their prescriptions phoned to a pharmacy than for those who returned to clinic for treatment (median 2.5 vs. 8 days). CONCLUSIONS: Where presumptive treatment was uncommon, providers were more likely to prescribe same-day therapy to symptomatic patients or those with TV on wet mount. Additional strategies are needed to improve the proportion of adolescent females treated in < or =7 days. PMID- 17868894 TI - Development of an HPV educational protocol for adolescents. AB - STUDY OBJECTIVES: To develop an educational protocol about HPV and Pap tests for adolescents, to evaluate the protocol for understandability and clarity, and to evaluate the protocol for its effectiveness in increasing knowledge about HPV. DESIGN: In phase 1, investigators and adolescents developed the protocol. In phase 2, adolescents evaluated the protocol qualitatively, investigators evaluated its effectiveness in increasing HPV knowledge in a sample of adolescents, and the protocol was revised. In phase 3, investigators evaluated the effectiveness of the revised protocol in an additional adolescent sample. SETTING: Urban, hospital-based teen health center. PARTICIPANTS: A total of 252 adolescent girls and boys in the three study phases. MAIN OUTCOME MEASURES: Pre- and post-protocol knowledge about HPV, measured using a 10- or 11-item scale. RESULTS: Scores on the HPV knowledge scale increased significantly (P < 0.0001) among adolescents who participated in phases 2 and 3 after they received the protocol. Initial differences in scores based on race, insurance type, and condom use were not noted post-protocol. CONCLUSION: The protocol significantly increased knowledge scores about HPV in this population, regardless of sociodemographic characteristics and risk behaviors. Effective, developmentally appropriate educational protocols about HPV and Pap tests are particularly important in clinical settings as cervical cancer screening guidelines evolve, HPV DNA testing is integrated into screening protocols, and HPV vaccines become available. In-depth, one-on-one education about HPV may also prevent adverse psychosocial responses and promote healthy sexual and Pap screening behaviors in adolescents with abnormal HPV or Pap test results. PMID- 17868895 TI - Bacterial colonization in suspected sexually abused children. AB - OBJECTIVE: Previous studies concluded that symptomatic prepubertal children with Gardnerella vaginalis infection should be investigated for child sexual abuse. Gardnerella vaginalis is only one out of a group of organism that cause bacterial vaginosis. The aim of the study was to report the frequency of bacterial colonization as well as sexually transmitted diseases and to correlate these data with patient characteristics. METHODS: Data were collected from 1996 to 2006. Medical records of 180 girls, median age at first sexual abuse 7.44 years (range 1-16, SD 3.937), have been evaluated retrospectively. SPSS software 12.0 has been used for statistical analysis. RESULTS: Only 18.3% of patients complained of vaginal discharge or pruritus. Sexually transmitted diseases were documented: Gonorrhoea 1 (1.8%, 56 tested), Chlamydia trachomatis 1 (1.6%, 62 tested), Syphilis 0 (0%, 5 tested), Trichomonas vaginalis 1 (0.7%, 136 tested) and HIV 0 (0%, 27 tested). Bacterial colonization were documented (121 tested): Gardnerella vaginalis 29 (24%), Enterobacteriaceae 50 (41.3%), Haemophilus influenzae 11 (9.1%), Streptococcus a haemolyticus 35 (28.9%), Streptococcus Group B 8 (6.6%), Staphylococcus Koag neg. 37 (30.6%), Staphylococcus aureus 10 (8.3%), Pseudomonas aeruginosa 4 (4.1%), Bacteroides 19 (15.7%), Prevotella 24 (19.8%), Klebsiella 4 (3.3%), Corynebacteria 20 (16.5%) and Ureaplasma 9 (7.4%). CONCLUSIONS: Sexually transmitted diseases are infrequent in children suspected for child sexual abuse. Bacterial colonization is common, however, not correlated with clinical symptoms (except for Bacteroides) and hymenal/vaginal injuries. PMID- 17868896 TI - Bone density in adolescents treated with a GnRH agonist and add-back therapy for endometriosis. AB - STUDY OBJECTIVE: To evaluate the bone density of adolescents with endometriosis treated with a GnRH-agonist and "add-back" therapy with norethindrone acetate. DESIGN: Retrospective chart review. SETTING: Pediatric gynecology clinic at a tertiary care center. PARTICIPANTS: 36 adolescents, ages 13 to 21 years, with endometriosis. MAIN OUTCOME MEASURES: Bone mineral density (BMD, g/cm(2)) by dual energy x-ray absorptiometry (DXA); BMD Z-scores of hip and spine. RESULTS: The mean BMD Z-score at the total hip was -0.24 +/- 1.0, with a range of -2.4 to 1.7. At this site, 6 subjects had a BMD Z-score between -1.0 and -2.0 SD, while 2 had a Z-score < or = -2.0 SD. The mean BMD Z-score at the lumbar spine was 0.55 +/- 1.1, with a range of -2.8 to 1.4. At the spine, 11 subjects had a BMD Z-score between -1.0 and -2.0 SD, while 3 had a Z-score < or = -2.0 SD. There was no correlation noted between duration of therapy with the GnRH-agonist plus add-back and BMD at the hip or spine. CONCLUSION: BMD at the hip was normal in most adolescents with endometriosis who were receiving a GnRH-agonist plus add-back therapy with norethindrone acetate. Almost one third of subjects exhibited skeletal deficits at the spine. These data suggest that BMD should be carefully monitored in adolescents receiving treatment with GnRH agonists. PMID- 17868897 TI - More than just vaginal intercourse: anal intercourse and condom use patterns in the context of "main" and "casual" sexual relationships among urban minority adolescent females. AB - PURPOSE: Receptive anal intercourse has long been recognized as a risk factor for the transmission of HIV and STIs. Most HIV/STI prevention messages continue to emphasize penile-vaginal transmission, so many teens do not recognize anal intercourse as risky sexual behavior. This purpose of this study was to determine the prevalence of anal intercourse, and to describe the relationship between types of sexual relationships (main vs. casual), types of sexual behaviors (vaginal vs. anal sex), and types of contraception used among inner-city sexually experienced adolescents. METHODS: Reproductive health histories were obtained from 350 sexually experienced adolescent females aged 12-18 years participating in a 5-year STI acquisition study at an urban health center. Baseline sexual behavior data was analyzed and described using frequencies, percentages and chi square tests. RESULTS: 41% of teens and 86.5% of teens reported engaging in sexual activity with casual and main partners respectively. Sixteen percent of teens with main partners and 12% of those with casual partners engaged in receptive anal intercourse (P = 0.31). Condom use is more prevalent for both vaginal (61% vs. 32.4%, P < or = 0.0001) and anal (47.1% vs. 21.3%, P = 0.0428) intercourse in the context of casual as compared to main sexual relationships. Teens involved in a casual relationship were more likely to use anal intercourse as a form of contraception (41.2% vs. 8.5%, P = 0.0022). CONCLUSION: It is imperative that health care providers recognize that adolescents engage in anal sex, specifically inquire about their types of sexual behavior and types of sexual relationships so that anticipatory guidance regarding HIV/STI transmission risk reduction education can be tailored to meet their needs. PMID- 17868898 TI - Perrault syndrome with Marfanoid habitus in two siblings. AB - BACKGROUND: Familial pure gonadal dysgenesis with 46 XX karyotype and sensorineural deafness constitutes a rare autosomal recessive syndrome described initially by Perrault in 1951. The spectrum of the disease remains undetermined. Families with additional newer findings are regularly reported. CASE: We report two siblings with gonadal dysgenesis, progressive sensorineural deafness, Marfanoid body proportions and skeletal features, and a normal female karyotype. The diagnosis of Perrault syndrome was made. Abnormal body proportions including a longer arm span, shorter trunk, high arched palate, long slender fingers and positive thumb and wrist sign were observed. The siblings did not have any cardiac or ocular features of Marfan's syndrome. CONCLUSION: The report of the siblings adds to the expanding spectrum of findings in Perrault syndrome. PMID- 17868899 TI - Erythema multiforme limited to the oral mucosa in a teenager on oral contraceptive therapy. AB - BACKGROUND: Erythema multiforme has been linked to numerous drugs and infectious agents. A link to oral contraceptive use has been reported in the past in the adult population but thus far has not been reported in children or adolescents. CASE: We report the case of an 18-yr-old female who developed oral erosions consistent with erythema multiforme two and a half weeks after initiating therapy with an oral contraceptive agent. A thorough examination for other inciting factors was negative, and the lesions slowly resolved over the course of 3 weeks. CONCLUSIONS: This case illustrates that erythema multiforme should be considered in the differential diagnosis of adolescents with oral erosions who have been prescribed oral contraceptives. PMID- 17868900 TI - Streptococcus pyogenes pharyngeal colonization resulting in recurrent, prepubertal vulvovaginitis. AB - BACKGROUND: Recurrent, prepubertal, vaginal infections are an uncommon, troublesome problem for the patient and her family. Failure of initial therapy to alleviate vulvovaginitis may be related to vulvar skin disease, foreign body, sexual abuse, pinworms, reactions to medications, anatomic anomalies, or allergies. This report describes a case of recurrent Streptococcus pyogenes vulvovaginitis secondary to presumed vaginal re-inoculation from pharyngeal colonization. CASE: A 4-yr-old presented with one year of culture proven, recurrent Streptococcus pyogenes vulvovaginitis. Her symptoms repeatedly resolved with penicillin therapy, but continued to recur following cessation of antibiotic therapy. Evaluation included physical examination, trans-abdominal pelvic ultrasound, and vaginoscopy which all revealed normal upper and lower genital tract anatomy. Both the patient and her mother demonstrated culture proven, Group A Streptococcus pharyngeal colonization. Because of the possibility of repeated inoculations of the vaginal area from the colonized pharynx, they were both treated for decolonization with a regimen of amoxicillin and rifampin for ten days. Following this therapy there was resolution of vaginal symptoms with no further recurrence. Follow-up pharyngeal culture done on both mother and child on their last visit were negative for Group A Streptococcus. CONCLUSION: This case demonstrated an unusual specific cause of recurrent vaginitis resulting from presumed self or maternal re-inoculation with group A beta-hemolytic streptococcus from pharyngeal colonization. Group A beta-hemolytic streptococcus are consistently sensitive to penicillin, but up to 25% of acute pharyngitis cases treated with penicillin having continued asymptomatic, bacterial carriage within the nasopharynx. Thus initial alleviation of symptoms in a patient with Group A beta-hemolytic vulvovaginitis treated with penicillin, can have continued asymptomatic pharyngeal colonization which can result in recurrence of the vulvovaginitis. This case stresses the importance of considering re-infection through this route in the patient with recurrent Group A beta-hemolytic streptococcus vulvovaginitis. PMID- 17868901 TI - Immunohistopathological and biochemical changes in Schistosoma mansoni-infected mice treated with artemether. AB - OBJECTIVE: To investigate immune mechanisms possibly involved in the amelioration of histopathological changes in livers of Schistosoma mansoni-infected mice treated with artemether (ART), including liver functions and apoptotic changes. METHODS: Male CD-1 Swiss albino mice were infected with Schistosoma mansoni and treated with praziquantel (PZQ) 6 weeks post-infection (PI) (500 mg/kg/day x2) and/or ART in double dose (each of 400 mg/kg) 4 and 6 weeks PI. Parasitological parameters, liver functions and histopathological changes including T-lymphocyte profile and apoptotic changes were assessed. RESULTS: Eight weeks PI, although the reduction in worm burden in mice treated with ART plus PZQ was comparable to that in PZQ-treated mice, yet there was complete absence of eggs and typical granulomas. The ratio of T-helper/cytotoxic cells was in favor of T-helper in infected control and in mice treated with both drugs. This ratio was 0.9:1 and 0.7:1 in PZQ and ART-treated groups, respectively, with moderate apoptotic changes in the latter. All biochemical parameters expressing liver function were improved with all treatment regimens. CONCLUSIONS: Administration of ART in addition to PZQ resulted in absence of eggs and typical granulomas with less apoptotic changes than in ART-treated mice. Improved liver functions with higher apoptosis in ART-treated mice may suggest enhanced necrotic cell death/regenerative changes. PMID- 17868903 TI - A relationship between neurocognitive impairment and functional impairment in bipolar disorder: a pilot study. AB - We assessed the relationship between neurocognitive status and role function in 14 euthymic bipolar subjects. Role function scores were bimodally distributed. Poor verbal memory and executive function were associated with functional impairment, suggesting that functional disability may be restricted to a subgroup of cognitively impaired bipolar patients. PMID- 17868904 TI - Characterization and expression analysis of TNFR-associated factor 1 (TRAF1) in grass carp Ctenopharyngodon idella. AB - TNF receptor associated factor 1 (TRAF1) plays an important role in regulating the TNF signaling and protecting cells from apoptosis. In the present study, a TRAF1 gene has been cloned from grass carp (Ctenopharyngodon idella) by reverse transcription (RT)-PCR and rapid amplification of cDNA ends (RACE). The full length cDNA is 2235bp, including a 250bp 5' UTR (untranslated region), a 1659bp open reading frame, and a 326bp 3' UTR. The polyadenylation signal (AATAAA, AATAA) and one mRNA instability motif (AUUUA) were found followed by a poly (A) tail in the 3' UTR. No signal peptide or transmembrane region has been found in the putative amino acids of grass carp TRAF1 (gcTRAF1). The putative amino acids of gcTRAF1 share 72% identity with the homologue in zebrafish. It is characterized by a zinc finger at the N-terminus and a TRAF domain (contains one TRAF-C and one TRAF-N) at the C-terminus. The identity of the TRAF domain among all the TRAF1 homologues in vertebrates varies from 52% to 58%, while the identities of TRAF-C were almost the same as 70%. The recombinant gcTRAF1 has been constructed successfully and expressed in Escherichia coli by using pET-32a expression vector. The polyclonal antibody for rabbit has been successfully obtained. The expression of gcTRAF1 in different organs was examined by real-time quantitative PCR and Western blotting, respectively. It was widely distributed in heart, head kidney, thymus, brain, gill, liver, spleen, and trunk kidney. This is the first report of TRAF1 homologue molecule found in fish. PMID- 17868905 TI - Phenotypic and functional characterisation of porcine CD4(+)CD25(high) regulatory T cells. AB - Over the last years regulatory T cells (Tregs) were defined as CD4(+)CD25(+) T lymphocytes expressing the transcription factor Foxp3 (Forkhead Box P3) with the ability to downregulate various immune responses. In swine the existence of CD4(+)CD25(+) T lymphocytes was described before but nothing is known about the function of this minor cell population to date. Therefore, we studied porcine CD4(+)CD25(+) T cells with regard to major attributes of murine and human Tregs: their phenotype concerning the expression of several T-cell specific antigens, including Foxp3, their IL-10 production and their suppressive capacity. Our results revealed that porcine CD4(+)CD25(+) T cells with high CD25 expression count for about 2-9% of the CD4(+) T-cell subset. They demonstrate a strong Foxp3 expression, a heterogeneous CD45RC-, CD8alpha- and MHC-II-defined phenotype and a moderate IL-10 production. Co-cultivation of increasing numbers of CD4(+)CD25(high) T cells with a constant number of CD4(+)CD25(-) responder-T cells caused a decrease in proliferation of the entire culture. This demonstrates the suppressive capacity of the CD4(+)CD25(high) T-cell subset and - together with their Foxp3 expression - the existence of porcine Tregs. PMID- 17868906 TI - Recombined CC chemokine ligand 2 into B16 cells induces production of Th2 dominant [correction of dominanted] cytokines and inhibits melanoma metastasis. AB - This study is aimed to verify whether CCL2 can induce Th2 polarization in vivo and subsequently inhibit tumor metastasis. B16 cells (a murine melanoma cell line) highly expressing CCL2 (CCL2-B16 cells) were obtained by transfection with recombinant plasmid CCL2-pcDNA3. Primary thymocytes were co-cultured with CCL2 B16 cells and STAT-6-mediated Th2 polarization was noticed after co-culture. Caudal vein injection of CCL2-B16 cells effectively inhibited pulmonary metastasis in C57BL/6 mice, but not in nude mice, indicating that T cells play a role in CCL2-induced inhibition of tumor metastasis. We found that high level of CCL2 up-regulated the expression of Th2-related cytokine (IL-4) in tumor microenvironment and increased CD4+, CD8+, and CD45RB+ cells in the peripheral blood and tumor tissues. We also demonstrated that inoculation of mice with CCL2 B16 cells prolonged mice survival time when they were reinjected with wildtype B16 cells, implying that CCL2 can activate immuno-memory in mice. It is concluded that high expression of CCL2 can induce Th2 polarization in tumor microenvironment and can effectively inhibit tumor metastasis, which casts new lights on the role of chemokines in reconstruction of immune surveillance in patients suffering from tumors. PMID- 17868902 TI - Dynorphin and the pathophysiology of drug addiction. AB - Drug addiction is a chronic relapsing disease in which drug administration becomes the primary stimulus that drives behavior regardless of the adverse consequence that may ensue. As drug use becomes more compulsive, motivation for natural rewards that normally drive behavior decreases. The discontinuation of drug use is associated with somatic signs of withdrawal, dysphoria, anxiety, and anhedonia. These consequences of drug use are thought to contribute to the maintenance of drug use and to the reinstatement of compulsive drug use that occurs during the early phase of abstinence. Even, however, after prolonged periods of abstinence, 80-90% of human addicts relapse to addiction, suggesting that repeated drug use produces enduring changes in brain circuits that subserve incentive motivation and stimulus-response (habit) learning. A major goal of addiction research is the identification of the neural mechanisms by which drugs of abuse produce these effects. This article will review data showing that the dynorphin/kappa-opioid receptor (KOPr) system serves an essential function in opposing alterations in behavior and brain neurochemistry that occur as a consequence of repeated drug use and that aberrant activity of this system may not only contribute to the dysregulation of behavior that characterizes addiction but to individual differences in vulnerability to the pharmacological actions of cocaine and alcohol. We will provide evidence that the repeated administration of cocaine and alcohol up-regulates the dynorphin/KOPr system and that pharmacological treatments that target this system may prove effective in the treatment of drug addiction. PMID- 17868907 TI - NGF promotes microglial migration through the activation of its high affinity receptor: modulation by TGF-beta. AB - Activation and mobilization of microglia are early events in the majority of brain pathologies. Among the signalling molecules that can affect microglial behaviour, we investigated whether nerve growth factor (NGF) was able to influence microglial motility. We found that NGF induced chemotaxis of microglial cells through the activation of TrkA receptor. In addition, NGF chemotactic activity was increased in the presence of low concentrations (< or =0.2 ng/ml) of transforming growth factor-beta (TGF-beta), which at this concentration showed chemotactic activity per se. On the contrary, NGF-induced microglial migration was reduced in the presence of chemokinetic concentration of TGF-beta (> or =2 ng/ml). Finally, both basal and NGF-induced migratory activity of microglial cells was increased after a long-term exposure of primary mixed glial cultures to 2 ng/ml of TGF-beta. Our observations suggest that both NGF and TGF-beta contribute to microglial recruitment. The chemotactic activities of these two pleiotropic factors could be particularly relevant during chronic diseases in which recruited microglia remove apoptotic neurons in the absence of a typical inflammatory reaction. PMID- 17868909 TI - Inheritance of microtia in the Finnish population. AB - OBJECTIVE: To study the inheritance of microtia in the Finnish population, identify families for genetic linkage analyses and compare the phenotype between sporadic and familial patients. METHODS: Retrospective case series and patient questionnaire of 109 microtia patients referred for reconstruction of the earlobe to the Helsinki University Central Hospital during the years 1980-2005. RESULTS: 22 out of the 109 patients had a relative with microtia or preauricular tag. The familial and sporadic patients did not differ in microtia phenotype or sex distribution. Urinary system anomalies were statistically more prevalent in familial patients (p<0.01). The analyses of the birthplace of parents or grandparents of familial or sporadic microtia patients resulted in no evidence for founder effect. CONCLUSIONS: The prevalence of familial microtia/OAVS in the Finnish population is higher than 20%. The sporadic and familial microtia/OAVS patients do not differ in the phenotype or sex distribution. The mode of inheritance seems to be autosomal dominant with incomplete penetrance. PMID- 17868908 TI - Antiphospholipid antibodies in blood and cerebrospinal fluids of patients with psychosis. AB - Antiphospholipid antibodies (aPL) have been reported in the cerebrospinal fluids (CSF) of neurology patients but no CSF studies with psychiatric patients exist. We tested serum from 100 hospitalized psychotic patients having hallucinations and/or delusions for aPL. Patients with positive serum aPL findings were asked to submit CSF for aPL testing. Five CSF samples had aPL specificities not found in the patient's serum suggesting the possibility of intrathecal synthesis. Specificity and isotype discordance between CSF and blood aPL in these psychiatric patients implicates a central nervous system independent autoimmune process that may have an underlying association with the pathophysiology of their diseases. PMID- 17868910 TI - HIV-1 DNA vaccine efficacy is enhanced by coadministration with plasmid encoding IFN-alpha. AB - Numerous strategies have been employed in an attempt to improve the immunogenicity and efficacy of nucleic acid vaccines. In the present study, the immunogenicity in the induction of humoral and cellular immune responses to HIV-1 DNA vaccine expressing a chimeric gene of gag and gp120 and the adjuvant effect of IFN-alpha on HIV-1 DNA vaccine were studied in a murine model. The DNA vaccine plasmid pVAX1-gag-gp120 and eukaryotic expression plasmid pVAX1-IFN were constructed by inserting the chimeric gene of gag and gp120 of HIV-1 and IFN alpha into the downstream of CMV promoter of eukaryotic expression vector pVAX1, respectively. In vitro expression detected by RT-PCR and Western blotting showed that the genes of interest could be expressed in transfected HeLa cells. After BALB/c mice were immunized by three intramuscular inoculations of the HIV-1 DNA vaccine plasmids alone or in combination with IFN-alpha expression plasmids, the different levels of anti-HIV-1 humoral and cellular responses were measured comparable to the control groups immunized with pVAX1-IFN, parent plasmid pVAX1 or PBS. The percentage of CD3+CD4+ and CD3+CD8+ subgroups of spleen T lymphocytes and the specific cytotoxicity activities of splenic CTLs in the coinoculation group were significantly higher than those in the separate inoculation group, and an enhancement of antibody response was also observed in the coinoculation group compared with the separate inoculation group. Take together, coadministration of HIV-1 DNA vaccine plasmids and IFN-alpha expression plasmids can elicit stronger humoral and cellular immune responses in mice than HIV-1 DNA vaccine plasmids alone, and IFN-alpha can be an effective immunological adjuvant in DNA vaccination against HIV-1. PMID- 17868911 TI - A single-tube PCR assay for detecting viruses and their recombinants that cause tomato yellow leaf curl disease in the Mediterranean basin. AB - Tomato yellow leaf curl disease (TYLCD) is well known in Mediterranean countries, where it has been causing severe losses in tomato crops for decades. Until recently, two viruses (with several isolates) in the genus Begomovirus, family Geminiviridae, have been associated with the epidemics: Tomato yellow leaf curl virus (TYLCV) and Tomato yellow leaf curl Sardinia virus (TYLCSV). However, recombinants between these, such as Tomato yellow leaf curl Malaga virus (TYLCMalV), are spreading, and new methods for detecting all viruses present in the region are needed. By considering all DNA sequences available of viruses causing TYLCD in the Mediterranean basin, a PCR/RFLP protocol was developed that amplifies the intergenic region in a multiplex reaction, followed by digestion with AclI (=Psp1406I) restriction enzyme. This procedure generates an easily recognizable pattern on gels, with DNA fragments of specific size for each virus species and each recombinant: 800 bp for TYLCSV, 410 bp for TYLCV, 570 bp for TYLCMalV and the other detected recombinants, 640 bp for hypothetical recombinants of different type. This new method gives, with a single reaction, an overview of the species present in the sample and will be useful for screening the causal agents of TYLCD, as well as in breeding programs for resistance. PMID- 17868912 TI - Development of a multiplex PCR method for detecting and typing human papillomaviruses in verrucae vulgaris. AB - The methods for detecting and typing human papillomavirus (HPV) in most molecular epidemiological surveys of verrucae vulgaris were based on PCR followed by sequencing or hybridization. However, the amplification efficacies of different assays for the detection of HPV DNAs varied largely. In this study, a novel multiplex PCR method to detect and type the HPVs (HPV-1, -2, -27 and -57) related to verrucae vulgaris was described. This method allows detecting and typing HPV DNA simultaneously in one reaction based on the length of the PCR products after electrophoresis. The sensitivity and specificity of this multiplex PCR method was assessed with the standard template panels and the spiking sample panels, and evaluated with the clinical samples, compared with PCR assay with primer MY09/11. The results showed the novel method had reliable clinical sensitivity (97.6%) and specificity (100%), significantly higher than that of the PCR using consensus primer, MY09/11. In addition, this method can effectively detect multiple HPV infection within the lesions. This simplified, economic and time-saving multiplex PCR method provides a useful additional tool for the clinical epidemiological study of verrucae vulgaris. PMID- 17868913 TI - Forensic application of Epstein-Barr virus genotype: correlation between viral genotype and geographical area. AB - Using 50 forensic blood samples, the latent membrane protein 2A (LMP-2A) gene of Epstein-Barr virus (EBV) DNA was amplified to find a geographic correlation among the EBV genotypes. EBV DNA was detected in nine samples. From a phylogenetic analysis using 18 reported sequences as a reference, six EBV subtypes (Ia, Ib, Ic IIa, IIb, and IIc) were found. Japanese isolates were included in subtypes Ia or IIa. All the Asian reference isolates, except isolate D6, were included in subtype Ia or IIa. Mediterranean, an Alaskan and other African isolates were included in types Ib, Ic, IIb and IIc. The EBV genotype in the LMP-2A gene was thus demonstrated as being correlated with the host's geographical location. Typing in the EBV-associated nuclear antigen 2 gene was not related to that in the LMP-2A gene. Detection of the EBV genotype in the LMP-2A gene may be useful for determining the geographical origins of unidentified cadavers. PMID- 17868914 TI - Detection of human papillomavirus types 45 and 51 by type-specific polymerase chain reaction. AB - Human papillomavirus (HPV) types 45 and 51 are both considered as high risk types for the development of human cervical cancer. To optimize the detection of these two types in clinical samples, HPV-45 and HPV-51 specific primers were designed to amplify respectively a 141bp and a 266bp fragment from the L1 gene by polymerase chain reaction (PCR). The sensitivity and the specificity of these two PCR reactions were determined using varying amounts of HPV DNA containing plasmids and negative and positive controls. Overall, the sensitivity for the HPV 45 plasmid DNA is 10fg, while for HPV-51 the sensitivity is 1fg. This is equivalent to approximately 100 and 10 HPV genome copies per PCR reaction, respectively. PMID- 17868915 TI - Specific detection of reverse transcription-loop-mediated isothermal amplification amplicons for Taura syndrome virus by colorimetric dot-blot hybridization. AB - The goal of this study was to develop a field diagnosis system based on isothermal reverse transcription-loop-mediated amplification (RT-LAMP) for shrimp Taura syndrome virus (TSV), placing emphasis on specific and simple detection of the LAMP amplicons. After a single-tube RT-LAMP reaction for TSV was established, colorimetric dot-blot hybridization (DBH) was adopted to detect signals only from the target-derived amplicons. The results showed that the modified DBH offered unambiguous and sensitive detection of the TSV RT-LAMP amplicons without the UV cross-linking and denaturation steps. Together, TSV RT-LAMP-DBH assay reached the same dilution point as reverse transcription-nested polymerase chain reaction agarose gel electrophoresis (RT-nPCR-AGE) for TSV detection. Specificity of the assay was demonstrated by the absence of DBH signal from yeast tRNA and various shrimp viruses. TSV RT-LAMP-DBH was applied to 125 Penaeus vannamei and demonstrated a very good concordance (kappa value, 0.823) with RT-nPCR-AGE assay in detection efficiency. Furthermore, a one-step guanidinium thiocyanate (GuSCN) homogenization method was established to provide RNA extraction efficiency comparable to that of the TRIzol Reagent for RT-LAMP. Requiring simply a heating apparatus, the GuSCN RNA extraction-isothermal RT-LAMP-DBH protocol has the potential for further development for diagnosis of diseases in the field. PMID- 17868916 TI - Microbiological diagnostic procedures in respiratory infections: suppurative lung disease. AB - Pursuing a microbiological diagnosis in suppurative lung disease can enable focused antibiotic therapy, identify pathogens of potential concern for infection control, and in some cases delineate a specific pathological process. Suppurative lung disease can be categorized as acute or chronic. Acute disease most commonly consists of lung abscess or parapneumonic empyema. The vast majority of chronic suppurative lung disease in childhood is due to cystic fibrosis. Samples from the respiratory tract offer the most useful information for diagnosis and management, but adjunctive information can also be obtained from serological methods, blood cultures and molecular techniques. The quality of respiratory tract samples is vital to aid accurate interpretation of results, and this varies according to the technique of collection. Antibiotic sensitivity testing is of particular importance in an era of evolving antibiotic resistance and can be problematical in cystic fibrosis. PMID- 17868917 TI - Congenital and neonatal pneumonia. AB - The greatest risk of death from pneumonia in childhood is in the neonatal period. It is estimated that pneumonia contributes to between 750000-1.2 million neonatal deaths annually, accounting for 10% of global child mortality. Congenital and neonatal pneumonias are often a difficult disease to identify and treat, with clinical manifestations often being non-specific. Many of the normal lung defences are compromised in the fetus and neonate, leading to an increased susceptibility to infection. The aetiology and epidemiology of congenital and neonatal pneumonias will depend on the clinical setting and population that the baby belongs to, the stage in the perinatal period, the gestational age of the baby and the definition of pneumonia. Diagnosis, treatment and prevention strategies are therefore also dependent on these factors, and will differ depending on the clinical setting. This review summarizes the current knowledge concerning congenital and neonatal pneumonia worldwide and discusses future directions in the prevention of the disease. PMID- 17868918 TI - Microbiological aspects of bacterial lower respiratory tract illness in children: typical pathogens. AB - Whilst childhood immunization programmes have had an impact on the spectrum of pneumonic diseases seen in children, bacteria remain an important cause of lower respiratory tract infection (LRTI), particularly in younger and debilitated children. Because of the difficulty in obtaining lower respiratory tract specimens in children, specific diagnosis has often been difficult, although advances in diagnostic techniques have provided a much greater range of tools for the clinician. The challenge is to understand the application and limitation of these tests in the diagnosis of LRTI. This review examines the microbiological and diagnostic issues around Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis and enteric Gram negative pathogens. PMID- 17868919 TI - Microbiological aspects of bacterial lower respiratory tract illness in children: atypical pathogens. AB - 'Atypical' lower respiratory tract pathogens often cause a distinct identifiable syndrome in adults, but in children the clinical presentation of atypical, typical and viral pneumonia is less well differentiated. Specific microbiological investigations are usually required, but an understanding of their strengths and weaknesses is necessary to make interpretation possible. This review examines clinical presentation, microbiology and current evidence surrounding diagnostic techniques for Mycoplasma pneumoniae, Chlamydophila pneumoniae, Chlamydophila psittaci, Bordetella pertussis and Legionella species. Applying an understanding of the investigations to the diagnosis of pneumonia in children may lead to more appropriate patient management by ensuring that they clarify rather than further obscure the diagnosis. PMID- 17868920 TI - Microbiological diagnostic procedures in respiratory infections: mycobacterial infections. AB - This article will review traditional and newer microbiological techniques for the diagnosis of mycobacterial respiratory infections. It will concentrate on the diagnosis of infections due to Mycobacterium tuberculosis, the main mycobacterium causing respiratory infections of clinical and public health importance. The diagnosis of respiratory disease associated with non-tuberculous mycobacteria (NTM), particularly in children with underlying airway pathology such as cystic fibrosis (CF) or bronchiectasis, will be briefly discussed. With respect to the diagnosis of tuberculosis (TB), the review will concentrate on the diagnosis of patients with symptoms and/or signs of clinical disease, rather than the detection of exposure or asymptomatic infection. It will not specifically address the assessment of pre-test probability based on clinical or epidemiological factors, the use of radiological investigations or the investigation of extrathoracic lymph node disease or chest wall disease. The role of newer diagnostic modalities including nucleic acid detection (NAD) and gamma-interferon assays in paediatric practice will be reviewed, and suggestions made as to how they may fit into contemporary diagnostic algorithms. PMID- 17868921 TI - Immunocompromised children: conditions and infectious agents. AB - Individuals with immunodeficiency, either primary or acquired, are increasingly common. These individuals have increased susceptibility to a range of infections which are uncommon in the normal host. An understanding of the individual's immune defect provides important information about the range of organisms that this individual may be susceptible to. As a corollary, identification of an 'opportunistic pathogen' may indicate the patient's type of underlying immune defect. PMID- 17868922 TI - Respiratory virus infections. AB - The respiratory tract is a frequent site of infection with a wide range of viruses. Each family of viruses can cause differing clinical syndromes depending on the age of the patient and the immune response. As a corollary, different clinical syndromes can be caused by different families of viruses. PMID- 17868923 TI - Clinical utility of synergy testing for multidrug-resistant Pseudomonas aeruginosa isolated from patients with cystic fibrosis: 'the motion for'. AB - Patients with cystic fibrosis are at risk of developing infections with multidrug resistant (MDR) pathogens, particularly Pseudomonas aeruginosa. Thus, there has been widespread interest in using antimicrobial agents in combination to expand the antimicrobial spectrum, prevent the emergence of resistance, reduce toxicity and provide synergistic activity. There are multiple methodologies for synergy testing, but checkerboard dilution assays and multiple combination bactericidal testing have been used most often for cystic fibrosis isolates. To date, synergy testing has been advocated to guide treatment for MDR strains of P. aeruginosa associated with a pulmonary exacerbation for which conventional testing does not reveal susceptibility to two agents from different classes of antibiotic. Synergy testing has also been advocated for isolates from patients failing to respond to therapy for treatment of a pulmonary exacerbation or from patients with substantial drug allergies for whom antibiotic choices are limited. PMID- 17868924 TI - Antibiotic synergy testing should not be routine for patients with cystic fibrosis who are infected with multiresistant bacterial organisms. AB - Patients with cystic fibrosis (CF) suffer from chronic bacterial infection of the airways, and many patients are infected with multiresistant bacteria. Combination antibiotic susceptibility tests, or antibiotic synergy tests, are in vitro tests that have been developed to allow clinicians to choose combinations of antibiotics that should be more effective at killing, or inhibiting, multiresistant bacterial pathogens. Only one randomised controlled clinical trial has been performed to determine whether combination antibiotic susceptibility testing leads to an improved clinical outcome for patients with acute pulmonary exacerbations of CF. The results of this clinical trial were disappointing - treatment based on combination antibiotic susceptibility testing was no more effective than treatment based on conventional culture and sensitivity testing. The adoption of antibiotic synergy testing as routine practice for patients with CF would be costly and would not be justified as there is insufficient evidence to suggest that the routine use of these tests improves clinical outcomes. PMID- 17868925 TI - Editorial overview: clinical utility of synergy testing for multidrug resistant Pseudomonas aeruginosa isolated from patients with cystic fibrosis. PMID- 17868926 TI - Multidrug resistant tuberculosis in a 6 year old child. AB - The case is reported of a 6 year old girl whose mother had multidrug resistant tuberculosis (MDR TB). The diagnostic algorithm and the pros and cons of treatment of MDR TB in a child are discussed. PMID- 17868927 TI - Measurement of nasal nitric oxide. AB - Nasal nitric oxide (nNO) is produced in high quantity in the upper airways. It is thought to be involved in host defence functions and regulation of mucociliary function, and to serve as a biochemical airborne transmitter. The measurement of nNO is easy and non-invasive. It has evolved as a screening test to exclude primary ciliary dyskinesia (PCD) in patients with suggestive symptoms, because nNO is extremely low in this condition. Nasal NO is also altered in other nasal, sinus and pulmonary pathologies, but is without diagnostic value outside of PCD. PMID- 17868928 TI - Neuraminidase inhibitor drug susceptibility differs between influenza N1 and N2 neuraminidase following mutagenesis of two conserved residues. AB - Neuraminidase (NA) inhibitors are a class of antivirals designed to target the conserved residues of the influenza NA active site. While there are many conserved residues in the NA active site that are involved in NA inhibitor binding, only a few have been demonstrated to confer resistance. As such, little is known regarding the potential of the other conserved residues in the NA active site to cause NA inhibitor resistance. Two conserved residues (E227 and E276) of an N1 NA that have not previously been associated with resistance to NA inhibitors were investigated. Site-directed mutagenesis was used to generate three alternative amino acids at each residue. Reverse genetics was used to generate recombinant mutant viruses which were characterized for growth, NA activity and NA inhibitor sensitivity. Of the six recombinant viruses expressing NA with mutations at either E227 or E276, only the E227D and E276D viruses were able to grow without supplementary NA activity, and all mutant viruses had a significant reduction in NA activity. The E227D virus demonstrated significantly reduced sensitivity to zanamivir while the E276D virus did not demonstrate any significant changes in NA inhibitor sensitivity. Interestingly, the resistance profiles of E227D and E276D in N1 NA were significantly different from these sites that have been reported for N2 NA. This study confirmed the essential role of NA active site residues in viral fitness, and identified clear differences in the role of residues E227 and E276 in NA inhibitor resistance with N1 and N2 neuraminidases. PMID- 17868929 TI - Dorsal hippocampal N-methyl-D-aspartate receptors underlie spatial working memory performance during non-matching to place testing on the T-maze. AB - Previous lesion studies have suggested a functional dissociation along the septotemporal axis of the hippocampus. Whereas the dorsal hippocampus has been implicated in spatial memory processes, the ventral hippocampus may play a role in anxiety. However, these lesion studies are potentially confounded by demyelination of fibres passing through the lesion site, and the possibility of secondary, downstream changes in associated brain structures as a consequence of their chronic denervation following the lesion. In the present study, we have used the microinfusion of muscimol to temporarily inactivate either the dorsal or ventral hippocampus in order to re-examine the contribution of the hippocampal sub-regions to spatial memory. Microinfusion studies spare fibres of passage and offer fewer opportunities for compensatory changes because the effects are transient and short-lasting. Rats were infused prior to spatial working memory testing on a non-matching to place T-maze alternation task. Spatial working memory was impaired by dorsal but not ventral hippocampal inactivation. In a second experiment, infusion of the NMDAR antagonist, D-AP5, into dorsal hippocampus also impaired spatial working memory performance, suggesting that NMDAR function within the dorsal hippocampus makes an essential contribution to this aspect of hippocampal information processing. PMID- 17868930 TI - Effect of parental morphine addiction on hippocampal long-term potentiation in rats offspring. AB - Attention to addiction of women alone for fetus and infant's health has caused the possible role of father's status was less considered, while some developmental impairments including decrease of liter size, weight loss, congenital deficiencies, behavioral disorders, and learning and memory impairments in offspring with addicted father have been reported. In this study the effects of addiction of one or both parents to morphine on male and female offspring hippocampal long-term potentiation (LTP), were assessed. One hundred twenty female and 48 male rats (4-5 months, 250-270 g) were used. Forty females and 16 males were addicted by oral administration of morphine (32 mg/kg twice daily) for 5 days before mating. Then each two males with five females were housed (coupled) per cage as five groups for coupling: (A) addicted females+5% dextrose males (add.F); (B) addicted males+5% dextrose females (add.M); (C) addicted females+addicted males (add.MF); (D) 5% dextrose females+intact males (dex.F); (E) 5% dextrose males+intact females (dex.M). In puberty offspring LTP was induced in hippocampal dentate gyrus by stimulation of perforant path (pp). Changes of population spikes (PS) amplitude and LTP slope at 0, 5, 30, 60 and 120 min were evaluated. Slope of LTP at 30, 60 and 120 min, and amplitude of PS at 60 and 120 min in add.F and add.M offspring were significantly lower than dextrose groups (P<0.01). LTP slope and PS amplitude of male and female offspring did not different between add.F and add.M groups. Our results suggest that both parental and paternal addiction to morphine may cause memory deficiency through reduction of LTP in hippocampus. PMID- 17868931 TI - Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa induced dyskinesias in parkinsonian monkeys. AB - Increased glutamatergic activity is believed to play a significant role in the development of levodopa-induced dyskinesias (LID). LID may therefore be attenuated by a reduction in glutamatergic function. This was tested pharmacologically in MPTP monkeys by increasing the formation of kynurenic acid (KYNA), a tryptophan metabolite that inhibits glutamate release and also blocks NMDA receptors directly. KYNA synthesis was stimulated by prolonged systemic administration of the kynurenine 3-hydroxylase inhibitor Ro 61-8048. Four MPTP cynomolgus monkeys received l-dopa (LD; 100mg) with benserazide (25 mg) for one month. Progressively, all these animals developed LID. Four other MPTP monkeys received Ro 61-8048 (50mg/kg) daily 3 h before administration of LD/benserazide for one month. The addition of Ro 61-8048 reduced the development of LID but did not affect the antiparkinsonian efficacy of LD. Moreover, Ro 61-8048 administration caused sustained increases in serum kynurenine and KYNA concentrations, which reverted to basal values 24 h after the last treatment. This effect of Ro 61-8048 was less pronounced in the CSF. These results demonstrate that long-lasting elevation of KYNA levels caused by prolonged inhibition of kynurenine 3-hydroxylase is associated with a significant reduction in LID but does not compromise the benefits of chronic LD therapy. PMID- 17868932 TI - Neuropeptide W in the rat pancreas: potentiation of glucose-induced insulin release and Ca2+ influx through L-type Ca2+ channels in beta-cells and localization in islets. AB - Neuropeptide W (NPW) is a regulatory peptide that acts via two subtypes of G protein-coupled receptors, GPR7 and GPR8. Evidence has been provided that NPW is involved in the central regulation of energy homeostasis and feeding behavior. In this study, we examined the effects of NPW on insulin release and localization of NPW in the rat pancreas. NPW (10-100 nM) significantly increased insulin release in the presence of 8.3 mM, but not 2.8 mM, glucose in the isolated rat islets. By fura-2 microfluorometry, NPW (1-100 nM) concentration-dependently increased cytosolic Ca(2+) concentration ([Ca(2+)](i)) at 8.3 mM glucose in rat single beta cells. The NPW-induced [Ca(2+)](i) increase was abolished under external Ca(2+) free conditions and by an L-type Ca(2+) channel blocker nifedipine (10 microM). RT-PCR analysis revealed that mRNA for NPW was expressed in the rat pancreas and hypothalamus. Double immunohistochemical analysis showed that NPW immunoreactivity was found in islets and co-localized with insulin-containing beta-cells, but not glucagon-containing alpha-cells and somatostatin-containing delta-cells. These results suggest that NPW could serve as a local modulator of glucose-induced insulin release in rat islets. NPW directly activates beta-cells to enhance Ca(2+) influx through voltage-dependent L-type Ca(2+) channels and potentiates glucose-induced insulin release. PMID- 17868933 TI - CSF orexin-A/hypocretin-1 concentrations in patients with intracerebral hemorrhage (ICH). AB - Orexins/hypocretins are neuropeptides that have various physiological effects, including the regulation of both the feeding behavior neuroendocrine functions and sleep-wakefulness cycle. Recent studies have suggested that the orexin system may also be involved in neuronal damage in the clinical setting and animal experiments. The aim of this study was to examine the role of the hypothalamic orexin-A/hypocretin-1 system in patients with intracerebral hemorrhage (ICH). The CSF orexin-A/hypocretin-1 levels were measured in 11 ICH patients. CSF orexin A/hypocretin-1 levels were low in ICH patients during the 13 days following the ICH event. The mean CSF orexin-A/hypocretin-1 levels were 61.1+/-22.3 (S.D.) pg/ml (range 27.5-106.9 pg/ml). The decreasing in the CSF orexin-A/hypocretin-1 levels was not related to the severity of ICH. The CSF orexin-A/hypocretin-1 levels were lower in the thalamic hemorrhage patients than those in other patients (48.5+/-23.3 pg/ml vs. 65.2+/-21.2 pg/ml; p=0.03.) These data indicate that orexin-A/hypocretin-1 may therefore play an important role in the various physiological responses including sleep, feeding, and the overall metabolism in ICH patients. PMID- 17868934 TI - Rac1-dependent transcriptional up-regulation of p27Kip1 by homophilic cell-cell contact in vascular endothelial cells. AB - The mechanism for the transcriptional up-regulation of p27Kip1 due to the formation of the cell-cell contact was investigated in vascular endothelial cells. The induction of the cell-cell contact by adding an extra number of endothelial cells activated Rac1, up-regulated p27Kip1 mRNA and protein, and also facilitated the cell cycle arrest. Transduction of the Rac1 inhibitor protein using the cell-penetrating peptide or treatment with a Rac1 inhibitor NSC23766 inhibited the p27Kip1 up-regulation and delayed the cell cycle arrest. Rac1 was therefore suggested to mediate the contact-induced transcriptional up-regulation of p27Kip1. The role of Rac1 in the regulation of the p27Kip1 promoter activity was next examined with a luciferase reporter assay. The promoter activity was increased by inducing the cell-cell contact, which was significantly inhibited by the Rac1 inhibitory protein and NSC23766. The evaluation of various truncated promoter regions determined region -620 to -573 nucleotides from the initiation codon to be responsible for the contact-induced, Rac1-dependent activation of the p27Kip1 promoter. The present study thus demonstrated for the first time that the activation of Rac1 due to the cell-cell contact plays a critical role in the transcriptional up-regulation of p27Kip1 in vascular endothelial cells. PMID- 17868936 TI - Analysis of drug-drug interactions (DDIs) in nursing homes in Central Taiwan. AB - With the progressive aging of the population, the long-term nursing care and drug safety for the elderly are gradually gaining attention. In Taiwan, nursing homes are the main institutes helping society or families take care of elderly people suffering from diseases. The aim of this study was to assess the prescribed medications of nursing home residents, the occurrence of DDIs and the association between the number of drugs and DDIs with a view to reinforce drug safety for the elderly. The findings of this study showed that the mean number of medications per resident was 5.74+/-2.4. Of the 323 samples, 81 (25.1%) had experienced DDIs, 63 (64.95%) were of moderate and 7 (7.2%) of major severity. The findings also showed that the number of potential DDIs increased as the number of medications used per residents increased. The residents with nine or more medications tended to have more DDIs, in comparison to those with one or two medications. The odds ratio (OR) was 11.389, which had reached statistical significance in difference. Therefore, to reduce potential DDIs, the number of medications for the senior people with chronic diseases should be properly controlled. PMID- 17868935 TI - Consequences of severity at stroke onset for health-related quality of life (HRQL) and informal care: a 1-year follow-up in elderly stroke survivors. AB - Severity of stroke influences the possibility of living at homes after stroke and has been discussed as one possible prognostic factor for functional outcome and future residence. The objective was to explore how severity at stroke onset affects health-related quality of life (HRQL) and informal care among 147 stroke survivors and their spouses living in their own homes 1 year after acute stroke. This study is part of "The Goteborg 70+ Stroke Study" which included 249 elderly persons after acute stroke. One year after stroke 59% of the survivors, 94 women and 53 men, lived in their own homes. This group forms the present study population. They were subdivided according to the severity of stroke at onset, as assessed by Barthel index (BI) ratings in the acute phase. The stroke survivors rated their HRQL and were interviewed in their own homes to assess the effects of stroke on daily life activities and informal care after 1 year. Informal caregivers were found to assist their spouses to a great extent, regardless of severity of stroke. Persons with moderate/severe stroke at onset received more informal as well as more formal help than the ones with mild stroke. As expected, the group with moderate/severe stroke also was more dependent on personal assistance, used more assistive devices (ADs) and rated their HRQL lower. However, persons who were assessed as mild stroke at onset also needed informal care, particularly with more complex tasks. Gender differences were obvious, since many women were living alone after their partner had died, while the men usually had assistance from their spouses. Noteworthy is that informal caregivers assisted their spouses to a large extent, regardless of severity of stroke at onset. Different kind of support programs, extended day rehabilitation centers and more relieve places should be developed. That could possibly improve the life situation for the elderly stroke survivors and their caregivers, generally an elderly spouse. PMID- 17868937 TI - Transmission parameters of Mycobacterium avium subspecies paratuberculosis infections in a dairy herd going through a control program. AB - A Johne's disease control program, including stringent management practices and a test-and-cull program (whole-herd fecal-samples taken twice a year), was implemented on a medium-sized Pennsylvania dairy farm that was suffering losses from clinical Johne's disease. The data that emerged from the control program, combined with birthdates, culling dates, lactation information and pedigrees, yielded an extensive longitudinal dataset. The dataset was processed through SAS 9.1 for statistical analysis; herd-level disease dynamics and dam-to-daughter transmission parameters were calculated. After the implementation of the program in 1984, prevalence dropped dramatically from 60% to less than 20% in 1989. After an apparent prevalence peak (25%) in 1991 due to improved test sensitivity, prevalence maintained a plateau of 10% from 1996 to 2000. After the implementation of the program, 9.5% of the offspring from test-negative dams and 26.8% of the offspring from known-infected dams became infected with Mycobacterium avium subspecies paratuberculosis (Map) (chi(2)=14.7; p=0.0001). Calves born shortly following the calving of an infected dam and calves growing up with a future high shedder were more likely to be infected compared to calves without this risk profile. It was concluded that, after the implementation of the control program, the most important causes of infections of susceptible calves were their own dams or infected animals which had calved recently. PMID- 17868938 TI - Effect of chronic treatment with clozapine and haloperidol on 5-HT(2A and 2C) receptor mRNA expression in the rat brain. AB - This study examined regional changes of 5-HT(2A and 2C) receptor mRNA expression in the rat brain after chronic administration of clozapine (1.5 mg/kg/day) and haloperidol (2.0 mg/kg/day) for 36 days. 5-HT(2A and 2C) receptor mRNA expression and distributions were detected by in situ hybridization after rats were sacrificed either 2 or 48 h after the last drug administration to examine both immediate and delayed effects following drug withdrawal. Following 2 h of drug withdrawal, it showed that clozapine administration significantly decreased 5 HT(2A) receptor mRNA, predominantly in the nucleus accumbens (65%), hippocampus (80%), lasteral septal nucleus (61%) and striatum (68%) compared to controls, whilst rebound increases were observed in most of these regions 48 h later. In contrast, no change in 5-HT(2A) receptor mRNA expression was found in the haloperidol treated groups either 2 h or 48 h after drug withdrawal. Clozapine also decreased 5-HT(2C) receptor mRNA expression in the posteromedial cortical amygdala (32%) and substantia nigra (35%) 2 h after the last drug administration, while rebound effects were also observed 48 h later. 5-HT(2C) receptor mRNA was only decreased in the substantia nigra at both 2 h (42%) and 48 h (54%) after the last haloperidol administration. Alterations in serotonin receptor expression in limbic system region such as the nucleus accumbens, hippocampus and lateral septal nucleus as well as the striatum may represent the specific regional targets that mediate the clinical effects of antipsychotics via the serotonin system. PMID- 17868939 TI - Growth/no growth models describing the influence of pH, lactic and acetic acid on lactic acid bacteria developed to determine the stability of acidified sauces. AB - Growth/no growth models were developed for two spoilage bacteria typical for acidified sauces, L. plantarum and L. fructivorans. Influencing factors embedded in the model are also those typically encountered in these acidified sauces. The pH was varied between 3.0 and 5.0 (5 levels), and the acetic and lactic acid concentration ranged from 0 to 3% (6 levels). Modified MRS broth was inoculated at a high inoculation level (10(6) CFU/ml), incubated at 30 degrees C and growth was assessed by optical density measurements. All combinations of environmental conditions were tested in twelvefold yielding precise values for the probability of growth. Data were modelled by means of ordinary logistic regression. A comparison was made between a model containing the total acid concentrations as explanatory variables, on the one hand, and a model differentiating between the dissociated and undissociated concentrations, on the other hand. Results showed that (i) L. plantarum and L. fructivorans behave differently, resulting in a clearly distinct growth/no growth interface, (ii) there was no great difference between the established models with different explanatory variables, (iii) in some cases, growth/no growth boundaries at very low probabilities (which are more practical in industry) show illogical behaviour. The results of this study were also compared with the CIMSCEE code, which is often used by food producers to determine the stability of their acidified food products. PMID- 17868940 TI - Development of biodegradable scaffolds based on patient-specific arterial configuration. AB - Biodegradable scaffolds are of great value in tissue engineering. We have developed a method for fabricating patient-specific vascular scaffolds from a biocompatible and biodegradable polymer, poly(L-lactide-co-epsilon-caprolactone). This method's usefulness is due to flexibility in the choice of materials and vascular configurations. Here, we present a way to fabricate scaffolds of human carotid artery by combining processes of rapid prototyping, lost wax, dip coating, selective dissolution, and salt leaching. The result was the successful development of porous biodegradable scaffolds, with mechanical strength covering the range of human blood vessels (1-3 MPa). Human umbilical vein endothelial cells were also cultured on the scaffolds and their biocompatibility was confirmed by cell growth. The Young's modulus of scaffolds could be controlled by changing polymer concentration and porosity. The wall thickness of the tubular scaffold was also controllable by adjusting polymer concentration and pull-up velocity during dip coating. We believe that this fabrication technique can be applied to patient-specific regeneration of blood vessels. PMID- 17868941 TI - Recycling of bacterial biomass in a process of L-threonine production by means of a recombinant strain of Escherichia coli. AB - The Gram-negative bacterium Escherichia coli B-3996 represents an interesting host organism for the production of the essential amino acid L-threonine. Microbial processes - especially those of aerobic cultivation - lead to the generation of considerable amounts of biomass, thus lowering the product yield. These are the reasons for studying methods for the recycling of biomass from E. coli. It will be shown that it is possible to disintegrate the microbial biomass preferably by means of high pressure homogenisation followed by a protease treatment of the resulting slurry of debris - in an efficient way and to recycle at least different amounts of the soluble part as cultivation medium component. By studying the growth and product formation of E. coli no adverse effects have been observed. PMID- 17868942 TI - Selection of reference genes for normalisation of specific gene quantification data of Aspergillus niger. AB - Aspergillus niger is a widely used expression host for homologous and heterologous protein production in biotechnological processes. In order to increase product yields, a thorough optimisation of these cultivation processes is necessary. Considering mRNA as the key molecule, which transports the genetic information between DNA and protein production side, the quantification of product specific gene expression provides useful information about product formation already on the level of transcription. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) is a powerful tool to obtain data about gene transcription. However, using this technique the choice of an appropriate reference system is a crucial aspect to provide optimal data normalisation. A prominent approach is the use of so called housekeeping genes as internal references. However, validation of the usability of these reference genes is the fundamental step before starting with qRT-PCR experiments. Adequate reference genes for A. niger have not been published so far. Therefore, 10 possible candidate genes from different functional classes were selected and their applicability as internal references validated. Transcript levels of these genes were compared in sets of 9, 41 and 19 samples from diverse cultivations of A. niger. Under the chosen experimental conditions, the genes act, sarA and cox5 have been identified as genes with the most stable gene expression. The three reference genes were used to normalise qRT-PCR data for glaA gene expression which showed a high correlation with glucoamylase production in continuous cultivations. PMID- 17868943 TI - Effects of the immobilization supports on the catalytic properties of immobilized mushroom tyrosinase: a comparative study using several substrates. AB - Mushroom tyrosinase was immobilized from an extract onto glass beads covered with one of the following compounds: the crosslinked totally cinnamoylated derivatives of glycerine, D-sorbitol, D-manitol, 1,2-O-isopropylidene-alpha-D-glucofuranose, D-glucuronic acid, D-gulonic acid, sucrose, D-glucosone, D-arabinose, D-fructose, D-glucose, ethyl-D-glucopyranoside, inuline, dextrine, dextrane or starch, or the partially cinnamoylated derivative 3,5,6-tricinnamoyl-D-glucofuranose which was obtained by the acid hydrolysis of 1,2-O-isopropylidene-alpha-d-glucofuranose. The enzyme was immobilized by direct adsorption onto the support and the quantity of tyrosinase immobilized was found to increase with the hydrophobicity of the supports. The kinetic constants of immobilized tyrosinase acting on the substrates, 4-tert-butylcatechol, dopamine and DL-dopa, were studied. When immobilized tyrosinase acted on 4-tert-butylcatechol, the values of K(m)(app) were lower than these obtained for tyrosinase in solution while, when dopamine and DL-dopa were used, the K(m)(app) were higher. The order of the substrates as regards their ionizable groups, DL-dopa (two ionizable groups)>dopamine (one ionizable group)>4-tert-butylcatechol (no ionizable group) coincided with the order of the K(m)(app) values shown by tyrosinase immobilized on the hydrophobic supports, and was the inverse of that observed for tyrosinase in solution. The K(m)(app) values of immobilized tyrosinase were in all cases higher than those of soluble tyrosinase and depended on the nature of the support and the hydrophobicity of the substrate, meaning that it is possible to design supports with different degrees of selectivity towards a mixture of enzyme substrates in the reaction medium. PMID- 17868944 TI - Substrate specificity of a galactose 6-phosphate isomerase from Lactococcus lactis that produces d-allose from d-psicose. AB - We purified recombinant galactose 6-phosphate isomerase (LacAB) from Lactococcus lactis using HiTrap Q HP and Phenyl-Sepharose columns. The purified LacAB had a final specific activity of 1.79units/mg to produce d-allose. The molecular mass of native galactose 6-phosphate isomerase was estimated at 135.5kDa using Sephacryl S-300 gel filtration, and the enzyme exists as a hetero-octamer of LacA and LacB subunits. The activity of galactose 6-phosphate isomerase was maximal at pH 7.0 and 30 degrees C, and enzyme activity was independent of metal ions. When 100g/L of d-psicose was used as the substrate, 25g/L of d-allose and 13g/L of d altrose were simultaneously produced at pH 7.0 and 30 degrees C after 12h of incubation. The enzyme had broad specificity for various aldoses and ketoses. The interconversion of sugars with the same configuration except at the C2 position was driven by using a large amount of enzyme in extended reactions. The interconversion occurred via two isomerization reactions, i.e., the interconversion of d-allose<-->d-psicose<-->d-altrose, and d-allose to d-psicose reaction was faster than d-altrose to d-psicose reaction. PMID- 17868945 TI - Effects of tensile and compressive strains on response of a chondrocytic cell line embedded in type I collagen gel. AB - Tensile and compressive strains are commonly used in mechanobiological models. Here we report on the development of a novel three-dimensional cell-culture method, which allows both tensile and compressive loads to be applied. Preliminary results were obtained using HCS2/8 chondrocytic cells embedded in type I collagen gel. This construct was subjected to either 16% tension or 14% compression. Confocal laser scanning microscopy showed that both tension and compression caused significant cell deformation. The collagen gel-embedded HCS2/8 cells were subjected to static tension, dynamic tension, static compression or dynamic compression for 24h. Dynamic compression led to significantly decreased 5 bromo-2'-deoxyuridine incorporation compared with the control group. PCR analysis revealed upregulation of type II collagen caused by dynamic tension, upregulation of aggrecan caused by static compression, and downregulation of type II collagen and aggrecan caused by dynamic compression. Nitric oxide production was significantly increased by static tension and static compression compared with the control group. Our experimental system effectively applied several types of strain to HCS2/8 cells embedded in collagen gel. Our results suggest that the mode of mechanical strain affects the response of HCS2/8 cells. PMID- 17868946 TI - Expressing Vitreoscilla hemoglobin in statically cultured Acetobacter xylinum with reduced O(2) tension maximizes bacterial cellulose pellicle production. AB - Vitreoscilla hemoglobin (VHb) was constitutively expressed in Acetobacter xylinum to enhance bacterial cellulose (BC) production. A pronounced enhancement of BC production in static culture was observed. Reducing O(2) tension in gaseous phase of the culture by tightly sealing the culture tube could also enhance BC production by 70%. O(2) tension in gaseous phase reduced from 21 to 15% in the sealed and static culture of VHb-expressing A. xylinum after 7 days cultivation, while 7.36g/l of BC with yield of 0.44 were obtained. BC pellicle production by VHb-expressing A. xylinum was successfully scaled-up in a sealed 4l disposable zip lock plastic bag with BC yield of 0.38 and concentration of 6.73g/l. PMID- 17868948 TI - Intravascular drug release kinetics dictate arterial drug deposition, retention, and distribution. AB - Millions of patients worldwide have received drug-eluting stents to reduce their risk for in-stent restenosis. The efficacy and toxicity of these local therapeutics depend upon arterial drug deposition, distribution, and retention. To examine how administered dose and drug release kinetics control arterial drug uptake, a model was created using principles of computational fluid dynamics and transient drug diffusion-convection. The modeling predictions for drug elution were validated using empiric data from stented porcine coronary arteries. Inefficient, minimal arterial drug deposition was predicted when a bolus of drug was released and depleted within seconds. Month-long stent-based drug release efficiently delivered nearly continuous drug levels, but the slow rate of drug presentation limited arterial drug uptake. Uptake was only maximized when the rates of drug release and absorption matched, which occurred for hour-long drug release. Of the two possible means for increasing the amount of drug on the stent, modulation of drug concentration potently impacts the magnitude of arterial drug deposition, while changes in coating drug mass affect duration of release. We demonstrate the importance of drug release kinetics and administered drug dose in governing arterial drug uptake and suggest novel drug delivery strategies for controlling spatio-temporal arterial drug distribution. PMID- 17868947 TI - The Varicella-zoster virus DNA encapsidation genes: Identification and characterization of the putative terminase subunits. AB - The putative DNA encapsidation genes encoded by open reading frames (ORFs) 25, 26, 30, 34, 43, 45/42 and 54 were cloned from Varicella-zoster virus (VZV) strain Ellen. Sequencing revealed that the Ellen ORFs were highly conserved at the amino acid level when compared to those of 19 previously published VZV isolates. Additionally, RT-PCR provided the first evidence that ORF45/42 was expressed as a spliced transcript in VZV-infected cells. All seven ORFs were expressed in vitro and full length products were identified using a C-terminal V5 epitope tag. The in vitro products of the putative VZV terminase subunits encoded by ORFs 30 and 45/42 proved useful in protein-protein interaction assays. Previous studies have reported the formation of a heterodimeric terminase complex involved in DNA encapsidation for both herpes simplex virus-type 1 (HSV-1) and human cytomegalovirus (HCMV). Here we report that the C-terminal portion of exon II of ORF45/42 (ORF42-C269) interacted in GST-pull down experiments with in vitro synthesized ORF30 and ORF45/42. The interactions were maintained in the presence of anionic detergents and in buffers of increasing ionic strength. Cells transiently transfected with epitope tagged ORF45/42 or ORF30 showed primarily cytoplasmic staining. In contrast, an antiserum directed to the N-terminal portion of ORF45 showed nearly exclusive nuclear localization of the ORF45/42 gene product in infected cells. An ORF30 specific antiserum detected an 87 kDa protein in both the cytoplasmic and nuclear fractions of VZV infected cells. The results were consistent with the localization and function of herpesviral terminase subunits. This is the first study aimed at the identification and characterization of the VZV DNA encapsidation gene products. PMID- 17868949 TI - Amanita phalloides poisoning: reassessment of prognostic factors and indications for emergency liver transplantation. PMID- 17868950 TI - The rise and fall(acy) of clinical directorates in Italy. AB - Clinical Directorates (CDs), in the sense of "intermediate organizational arrangements through which defined parts of larger hospitals health services are managed", were introduced in the Italian National Health Service (INHS) by law after the major reform of 1992. By means of such reform, accountability chains within INHS hospitals were streamlined. Changes looked at strengthening the role of management in hospitals as a strategy to improve efficiency in the provision of services. From this stream of managerialism emerged the attempts to re organize hospital activities along the lines of clinical directorates. The aim of this paper is to outline the context in which CDs initially developed in Italy as the "one best way" to address current hospital problems and the reasons why they are now challenged due to not coming up to expectations. To do so we run through the last 10 years of history of CDs in Italy and propose an interpretative framework to understand the grounds for their partial failure and success. PMID- 17868952 TI - VEGF121 promotes lymphangiogenesis in the sentinel lymph nodes of non-small cell lung carcinoma patients. AB - BACKGROUND: The sentinel lymph node (SLN) concept is that lymphatic flux from a primary tumor initially flows into a SLN. The mechanism mediating tumor metastasis within SLNs remains largely unknown; however, primary tumors overexpressing vascular endothelial growth factor (VEGF)-A appear to induce SLN lymphangiogenesis prior to metastasis in animal model. Our aim was to further investigate the capacity of VEGFs to induce lymphangiogenesis within SLNs and to assess their role in SLN metastasis in non-small cell lung carcinoma (NSCLC). METHODS: Real-time quantitative RT-PCR was used to assess expression of mRNAs encoding several VEGFs (VEGF121, VEGF165, VEGFR1, VEGFR2, VEGFR3, VEGF-C and VEGF D) in resected lymph node specimens from 35 NSCLC patients, after which we compared their expression SLNs and non-SLNs. In addition, expression of the lymphatic endothelium-specific hyaluronan receptor (LYVE)-1 was used to assess lymphangiogenesis in SLNs and non-SLNs. RESULTS: Immunohistochemical staining revealed substantial expression of LYVE-1 in SLNs. Moreover, levels LYVE-1 mRNA were significantly higher in SLNs than non-SLNs (P<0.05), as were levels of VEGF121 and VEGFR2 mRNA (P<0.01 and P=0.02, respectively). In addition metastasis positive SLNs showed significantly higher levels of VEGF121, VEGF-C and VEGF-D mRNA than metastasis-negative SLNs (P<0.001, P=0.01 and P=0.01, respectively), and VEGF121 induced the proliferation of lymphatic endothelial cells (P<0.01). CONCLUSIONS: Our findings suggest that active lymphangiogenesis is ongoing within SLNs from NSCLC patients, even before metastasis. This lymphangiogenesis may be promoted by upregulation of VEGF121, which may in turn act in part via induction of VEGF-C. PMID- 17868953 TI - Flavor-nutrient learning independent of flavor-taste learning with college students. AB - Flavor preference learning is mediated by associations with other liked tastes (flavor-taste learning) or calories (flavor-nutrient learning). The present study asked whether flavor-nutrient learning could be exhibited independent of flavor taste learning in humans (as has been shown in animals). Subjects were 24 undergraduates with a mean age of 19 years. Half the subjects received the bitter tasting cream cheese crackers with high fat cream cheese, half with low fat cream cheeses. Half the cream cheeses were flavored orange, half banana in each group. Results showed that subjects who had high fat flavored cream cheese rated the flavor more pleasant in plain crackers than subjects who had the flavor in low fat cream cheese (flavor-nutrient learning), although all cream cheese crackers were bitter tasting in training (flavor-taste learning). PMID- 17868951 TI - Spatiotemporal control over growth factor signaling for therapeutic neovascularization. AB - Many of the qualitative roles of growth factors involved in neovascularization have been delineated, but it is unclear yet from an engineering perspective how to use these factors as therapies. We propose that an approach that integrates quantitative spatiotemporal measurements of growth factor signaling using 3-D in vitro and in vivo models, mathematic modeling of factor tissue distribution, and new delivery technologies may provide an opportunity to engineer neovascularization on demand. PMID- 17868954 TI - Beyond pulmonary edema: diagnostic, risk stratification, and treatment challenges of acute heart failure management in the emergency department. AB - The majority of heart failure hospitalizations in the United States originate in the emergency department (ED). Current strategies for acute heart failure syndromes have largely been tailored after chronic heart failure guidelines and care. Prospective ED-based acute heart failure syndrome trials are lacking, and current guidelines for disposition are based on either little or no evidence. As a result, the majority of ED acute heart failure syndrome patients are admitted to the hospital. Recent registry data suggest there is a significant amount of heterogeneity in acute heart failure syndrome ED presentations, and diagnostics and therapeutics may need to be individualized to the urgency of the presentation, underlying pathophysiology, and acute hemodynamic characteristics. A paradigm shift is necessary in acute heart failure syndrome guidelines and research: prospective trials need to focus on diagnostic, therapeutic, and risk stratification algorithms that rely on readily available ED data, focusing on outcomes more proximate to the ED visit (5 days). Intermediate outcomes (30 days) are more dependent on inpatient and outpatient care and patient behavior than ED management decisions. Without these changes, the burden of acute heart failure syndrome care is unlikely to change. This article proposes such a paradigm shift in acute heart failure syndrome care and discusses areas of further research that are necessary to promote this change in approach. PMID- 17868955 TI - Synthesis, structure elucidation and identification of antitumoural properties of novel fused 1,2,4-triazine aryl derivatives. AB - Synthesis, structure elucidation and anticancer activities of novel fused 1,2,4 triazine aryl derivatives containing the ethoxycarbonyl (6-10) and carbohydrazide formations (11-15) are presented. Molecular structures of the synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR, EI-MS spectra and elemental analyses. Antitumour activities in vitro for heterobicyclic hydrazides of the type 11-14 were evaluated by BrdU method for human LS180, SiHa and T47D carcinoma cells. Amongst them, hydrazide 14 has exhibited remarkable inhibitory effect against SiHa and LS180 tumour cells, and simultaneously was found to be non-toxic towards the human normal cell line-HSF cells. Furthermore, the pulse field gel electrophoresis experiment was performed for characterizing DNA-cleaving activity of heterobicycle 14. The DNA fragments of 2500, 2000 and 500 kilobase pairs (kbp) were commonly detected in the cancer cell lines (SiHa, LS180 and T47D) treated with compound 14. DNA fragmentation pattern, since three types of fragments induced by the tested hydrazide of the type 14 were detected, suggesting a way of interaction with DNA. It is worth pointing out, that DNA strand breaks were also produced in human breast cancer (T47D) cells, a cell line where the induction of DNA fragmentation is very difficult. Moreover, the statistically significant apoptotic activity in T47D human breast cancer cells for the tested heterobicycle 14 was proved using the annexin V-binding assay. The antiproliferative properties in vitro for compounds 6-14 were evaluated by MTT method for human leukaemic Jurkat cells. Significant viability decreases in Jurkat cells treated with different concentrations of compounds 10 and 11 were observed, suggesting that these derivatives have antiproliferative activities. Their acute toxicities were established. For these compounds the influence on the central nervous system of mice in behavioural tests was examined. Molecular structure for free base of the intermediate 4 was confirmed by (1)H-(1)H COSY, HMBC and HMQC correlations. PMID- 17868956 TI - Dealing with stress: patterns of self-comfort among healthcare students. AB - Stress among healthcare students is a growing problem. As self-comfort is assumed to be a way of coping with stressful emotions, the aim of this study was to describe the patterns of self-comforting actions that healthcare students usually use in distress. One hundred and sixty-eight healthcare students volunteered to write down accounts of what they do when they comfort themselves. Their accounts were analysed using qualitative content analysis. The findings reveal two themes: Ingressing and Transcending. Ingressing comprises the sub-themes Unloading, Distracting, Nurturing oneself, Withdrawing and Reassuring. Transcending comprises the sub-themes Opening up and Finding new perspectives. These findings are in line with some stress-reducing strategies described in the literature on stress management. Winnicott's theory about the phenomenon of transition is used to interpret the findings. In the light of Winnicott's theory, self-comforting measures can be comprehended as the ability to transfer early childhood experiences of being nurtured and comforted into well-adapted strategies to effect relaxation and gain strength. PMID- 17868957 TI - Enhancement of immunity to an Escherichia coli vaccine in mice orally inoculated with a fusion gene encoding porcine interleukin 4 and 6. AB - Experiments were conducted to investigate the effect of a fusion gene of porcine IL-4 and IL-6 (PIL4/IL6) packaged with chitosan nanoparticles (CNPs) in terms of the development of a novel effective adjuvant. The IL4/PIL6 fusion gene was constructed and inserted into a eukaryotic expression vector. The plasmid was bound to CNP and then utilized to orally inoculate 21-day-old female Kunming mice that simultaneously received intramuscular injection of inactivated Escherichia coli vaccine. At 35 days post-vaccination, the mice were challenged by oral feeding with virulent O139: K88 strain EPEC E. coli bacteria. Compared with those of control mice, the content of immunoglobulins and specific antibodies to E. coli increased significantly in the sera of mice immunized with VPIL4/IL6-CNP (P<0.05). Furthermore, the levels of IL-2, IL-4 and IL-6 increased remarkably in the sera of immunized mice (P<0.05). After challenge, these immunological markers were elevated to different degrees in the mice immunized with the fusion gene construct (IL4/VPIL6-CNP) or individual plasmids (VPIL4+VPIL6-CNP). The immunized mice all survived the challenge and did not show any symptoms or lesion, whereas the VR1020-CNP control mice manifested obvious clinical symptoms and hemorrhagic lesions in the digestive tracts. These results demonstrated that VPIL4/IL6 entrapped with CNP is a novel promising adjuvant to promote specific immunity and resistance of animals against infectious pathogen. PMID- 17868959 TI - The absence of enhanced disease with wild type respiratory syncytial virus infection occurring after receipt of live, attenuated, respiratory syncytial virus vaccines. AB - Early in the development of respiratory syncytial virus (RSV) vaccines severe disease occurred in children after receipt of formalin-inactivated RSV vaccine. Continuing efforts to develop an appropriately attenuated and immunogenic live RSV vaccine have given opportunities to assure that live vaccines are safe through surveillance of children after vaccination. In the present study, the rate of RSV-associated upper respiratory tract illness in 388 children was lower in RSV vaccinated children than in controls (14% versus 20% in a 6-24 month old group and 16% versus 25% in infants). Additionally, there was no evidence that vaccination predisposed to more severe lower respiratory tract illness. Thus infection with a series of live attenuated RSV vaccines did not result in enhanced disease upon infection with wild type RSV. The impact of RSV during this surveillance will inform the design of future efficacy studies with RSV vaccines. PMID- 17868958 TI - HSV-1 amplicon vectors elicit polyfunctional T cell responses to HIV-1 Env, and strongly boost responses to an adenovirus prime. AB - HSV-1 amplicon vectors elicit strong T-cell responses to encoded antigens but the qualitative nature of these responses is poorly understood. Antigen-specific CD4(+) and CD8(+) T-cell responses to amplicon and adenovirus (rAd5) vectors encoding HIV-1 gp120 were assessed following immunization of mice, by performing intracellular cytokine staining for IFNgamma, IL2 and TNFalpha, following stimulation of splenocytes with a HIV-1 Env peptide pool. The quality of the primary T-cell response to amplicon and rAd5 vectors was strikingly similar, but there were qualitative differences in responses to amplicon vectors that incorporated different promoters upstream of gp120 - suggesting that promoters can significantly influence immune response quality. When prime-boost combinations were studied, a rAd5 prime and amplicon boost elicited the highest T cell response. Furthermore, protocols that incorporated a rAd5 prime consistently elicited a greater proportion of polyfunctional CD4(+) T-cells-regardless of boost. This suggests that initial priming can shape immune response quality after a boost. Overall, these findings provide insight into effective vector combinations for HIV-1 vaccine development. PMID- 17868960 TI - Higher peak contact hip stress predetermines the side of hip involved in idiopathic osteoarthritis. AB - BACKGROUND: Biomechanical parameters of the hip have been suggested to have an important influence on the development of osteoarthritis. We aimed to find out whether higher stress is generated in a hip that subsequently results in earlier hip arthroplasty compared to the contralateral hip in the same subject. METHODS: Standard anterior-posterior pelvic radiographs with no or subtle radiological signs of hip osteoarthritis, of 59 female patients, who underwent hip arthroplasty for primary osteoarthritis years later, were selected from the archives. For each subject peak contact hip stress of the hip with earlier arthroplasty and of the contralateral hip (pair of hips), was calculated from the radiographically obtained geometrical parameters with the HIPSTRESS program, which is based on a three-dimensional biomechanical model of the resultant hip force in the one-legged stance and a three-dimensional mathematical model of the contact hip stress distribution. Differences in peak contact hip stress within pairs of hips were determined for subjects with unilateral (22 pairs of hips) and bilateral disease (37 pairs of hips) by using paired-samples T-test. FINDINGS: In the population of subjects with unilateral osteoarthritis, average peak contact hip stress was significantly higher (P = 0.007) in hips with arthroplasty (2.44 kPa/N) than in contralateral hips (2.32 kPa/N). In the population of subjects with bilateral osteoarthritis, average peak contact hip stress was significantly higher (P<0.001) in hips with earlier arthroplasty (2.54 kPa/N) than in contralateral hips (2.35 kPa/N). INTERPRETATION: Results are consistent with the hypothesis that higher peak contact hip stress results in earlier hip arthroplasty due to faster development of idiopathic osteoarthritis. PMID- 17868961 TI - Relationship of medial plica and medial femoral condyle during flexion. AB - BACKGROUND: The goal of this study was to investigate the kinematic relationship between medial plica and medial femoral condyle during knee motion. METHODS: I prospectively selected 30 knees which had different size of medial plica from patients underwent arthroscopic surgery over a one-year-period. I located the inner margins of these plicae by inserting needles percutaneously under direct vision during arthroscopic examination. The topographic changes of the margins of these plicae during knee motion were recorded by fluoroscopy and analyzed. FINDINGS: Three types of medial plicae were defined by their size. In all types of the medial plicae, shifting (rubbing, sliding) medially was found when the knee was moved from extension to flexion. They remained in contact with the medial femoral condyles during the whole range of motion. INTERPRETATION: This observation disclosed the kinematic relationship of the medial plica with the medial femoral condyle during knee motion in vivo. This pattern of medial-lateral motion may generate some shearing force acting on the cartilage of the medial femoral condyle. The conclusion of this study may draw more attention to the role of medial plica in the pathogenesis of degeneration of the cartilage on the medial femoral condyle of the knee joint. PMID- 17868962 TI - Assessment of population exposure to particulate matter pollution in Chongqing, China. AB - To determine the population exposure to PM(10) in Chongqing, China, we developed an indirect model by combining information on the time activity patterns of various demographic subgroups with estimates of the PM(10) concentrations in different microenvironments (MEs). The spatial and temporal variations of the exposure to PM(10) were illustrated in a geographical information system (GIS). The population weighted exposure (PWE) for the entire population was 229, 155 and 211 microg/m(3), respectively, in winter, summer and as the annual average. Indoor PM(10) level at home was the largest contributor to the PWE, especially for the rural areas where high pollution levels were found due to solid fuels burning. Elder people had higher PM(10) exposure than adults and youth, due to more time spent in indoor MEs. The highest health risk due to particulate was found in the city zone and northeast regions, suggesting that pollution abatement should be prioritized in these areas. PMID- 17868963 TI - What do we (need to) know about the kinetic properties of nanoparticles in the body? AB - Nowadays the development and applications of nanotechnology are of major importance in both industrial and consumer areas. However, the knowledge on human exposure and possible toxicity of nanotechnology products is limited. To understand the mechanism of toxicity, thorough knowledge of the toxicokinetic properties of nanoparticles is warranted. There is a need for information on the absorption, distribution, metabolism and excretion (ADME) of nanoparticles and validated detection methods of these man-made nanoparticles. Determination of the ADME properties of nanoparticles requires specialised detection methods in different biological matrices (e.g. blood and organs). In this paper, the current knowledge on the kinetic properties of nanoparticles is reviewed. Moreover, knowledge gaps from a kinetic point of view (detection, dose, ADME processes) are identified. PMID- 17868964 TI - Socioeconomic status and health: youth development and neomaterialist and psychosocial mechanisms. AB - There is substantial debate in the field of epidemiology over the theoretical underpinnings of socioeconomic status (SES)-disease mechanisms in the developed world. In particular, it has been debated whether psychosocial mechanisms are important in understanding these relationships, compared with material influences. Within an interdisciplinary context, this review synthesizes the youth development and resilience literatures in examination of this hypothesis. This review provides evidence that both classes of mechanisms are critical to understanding and addressing SES-disease mechanisms over the lifecourse. Research findings demonstrating the effects of these classes of factors point to the complicated and dynamic nature of how SES may impact disease. In the epidemiologic literature, investigators predominantly consider the cumulative impact of biological insults over time. A developmental perspective, however, provides evidence of the importance of psychosocial influences early in life on socioeconomic and health trajectories over the lifecourse. Future epidemiologic research should consider cumulative and developmental influences of early adversity--both psychosocial and material--on later health. This perspective may be particularly relevant to appropriately evaluating the impact of selection and causation in research on SES and disease and will also hopefully provide clarity to this ongoing theoretical debate. PMID- 17868965 TI - Sequence analysis in multilevel models. A study on different sources of patient cues in medical consultations. AB - The aims of the study were to explore the importance of macro (patient, physician, consultation) and micro (doctor-patient speech sequences) variables in promoting patient cues (unsolicited new information or expressions of feelings), and to describe the methodological implications related to the study of speech sequences. Patient characteristics, a consultation index of partnership and doctor-patient speech sequences were recorded for 246 primary care consultations in six primary care surgeries in Verona, Italy. Homogeneity and stationarity conditions of speech sequences allowed the creation of a hierarchy of multilevel logit models including micro and macro level variables, with the presence/absence of cues as the dependent variable. We found that emotional distress of the patient increased cues and that cues appeared among other patient expressions and were preceded by physicians' facilitations and handling of emotion. Partnership, in terms of open-ended inquiry, active listening skills and handling of emotion by the physician and active participation by the patient throughout the consultation, reduced cue frequency. PMID- 17868966 TI - Toxicology and pharmacokinetics of 1-methyl-d-tryptophan: absence of toxicity due to saturating absorption. AB - 1-methyl-d-tryptophan (D-1MT) reverses the immunosuppressive effect of indoleamine 2,3-dioxygenase (IDO), and it is currently being developed both as a vaccine adjuvant and as an immunotherapeutic agent for combination with chemotherapy. The present study examined the pharmacokinetics and toxicity of D 1MT in preparation for clinical trials. Incubation of D-1MT in rat plasma for 24h produced no significant degradation, with <15% of D-1MT being bound to plasma protein. Following oral administration, D-1MT exhibited a larger AUC and V(d), longer elimination t(1/2), and slower clearance in rats than in dogs. When oral doses of D-1MT exceeded levels of 600 mg/m(2)/day in rats, or 1200 mg/m(2)/day in dogs, the C(max) and AUC values decreased, resulting in a corresponding decrease in oral bioavailability. Thus, the doses were indicative of the lowest saturating doses in dogs and rats corresponding with an elimination t(1/2) of 6.0 h and 28.7 h, a T(max) of 1h and 8h, and a bioavailability of 47% and 92%, respectively. Tissue concentrations of D-1MT in mice were highest in the kidney, followed by the liver, muscle, heart, lung, and spleen, respectively; 48 h post dosing, D-1MT was excreted in the urine (35.1%) and feces (13.5%). Oral administration of D-1MT in rats from 150 to 3000 mg/m(2)/day (25-500 mg/kg/day) and in dogs from 600 to 1200 mg/m(2)/day (30 and 60 mg/kg/day) for 28 consecutive days did not lead to mortality, adverse events, histopathological lesions, or significant changes in hematology, clinical chemistry, and body weight. These results suggested that 3000 and 1200 mg/m(2)/day were the no-observed-adverse-effect levels in rats and dogs, respectively. Mean plasma concentrations of D-1MT (600 and 1200 mg/m(2)/day) in dogs 1h post dosing were 54.4 and 69.5 microg/ml on Day 1, respectively, and 53.1 and 66.6 microg/ml on Day 28, respectively; thus, indicating no increase in plasma D-1MT with a change in dose. In conclusion, D 1MT has little toxicity when administered orally to rats and dogs. Exceeding the saturating dose of D-1MT is unlikely to cause systemic toxicity, since any further increase in D-1MT plasma levels would be minimal. PMID- 17868967 TI - Cinnamaldehyde inhibits pro-inflammatory cytokines secretion from monocytes/macrophages through suppression of intracellular signaling. AB - We investigated the in vitro anti-inflammatory effects of Cinnamaldehyde, a cytokine production inhibitor isolated from an essential oil produced from the leaves of Cinnamomum osmophloeum Kaneh, and its mechanism of action. Although Cinnamaldehyde has been reported to have contact sensitizing properties at high concentration (mM), we found that low concentration of Cinnamaldehyde (muM) inhibited the secretion of interleukin-1beta and tumor necrosis factor alpha within lipopolysaccharide (LPS) or lipoteichoic acid (LTA) stimulated murine J774A.1 macrophages. Cinnamaldehyde also suppressed the production of these cytokines from LPS stimulated human blood monocytes derived primary macrophages and human THP-1 monocytes. Furthermore, Cinnamaldehyde also inhibited the production of prointerleukin-1beta within LPS or LTA stimulated human THP-1 monocytes. Reactive oxygen species release from LPS stimulated J774A.1 macrophages was reduced by Cinnamaldehyde. The phosphorylation of extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase 1/2 induced by LPS was also inhibited by Cinnamaldehyde; however, Cinnamaldehyde neither antagonize the binding of LPS to the cells nor alter the cell surface expression of toll-like receptor 4 and CD14. In addition, we also noted that Cinnamaldehyde appeared to elicit no cytotoxic effect upon J774A.1 macrophages under our experimental conditions, although Cinnamaldehyde reduced J774A.1 macrophages proliferation as analysed by MTT assay. Our current results have demonstrated the anti-oxidation and anti-inflammatory properties of Cinnamaldehyde that could provide the possibility for Cinnamaldehyde's future pharmaceutical application in the realm of immuno-modulation. PMID- 17868968 TI - A method to assess 59Fe in residual tissue blood content in mice and its use to correct 59Fe-distribution kinetics accordingly. AB - BACKGROUND: Dysregulation of body iron-distribution may induce oxidative damage. To investigate the molecular mechanisms of iron homeostasis, corresponding essential genes are manipulated by many working groups. This asks for a simple method to pursue the resulting impact on body iron-distribution in mice. AIM: To develop a method for the assessment of (59)Fe in residual tissue blood content and to correct this influence in (59)Fe body distribution studies. METHODS: Iron status in male adult C57BL6 mice was adjusted by feeding diets with different iron content. Fractional contribution of organs to total body weight was determined after dissection. (59)Fe-labelled blood was injected in recipient mice to estimate total blood volume and residual blood content in all organs and tissues. The main experiment used these data to correct total (59)Fe tissue content at six intervals after (59)Fe injection (12h-28 days). RESULTS AND DISCUSSION: The sum of (59)Fe in all organs was the same as determined in each mouse before dissection. (59)Fe in whole blood remained constant from the 4th day after injection on, and was highest in iron-deficiency. As in other species, residual blood content was highest in spleen and lungs. Nevertheless, (59)Fe in the iron-deficient spleen decreased to zero and intestinal (59)Fe-content also decreased significantly over time after correction for (59)Fe in residual blood. These findings suggest correct assessment of compartment sizes and (59)Fe in residual blood in each organ. CONCLUSIONS: Differences in (59)Fe-distribution between iron status reflected changes in the expression of proteins of iron transport and its regulation correctly. Thus, the method seems suitable to analyse body iron-distribution in consequence to genetic manipulations of murine iron homeostasis which is a prerequisite to assess possible toxicological consequences of iron supplementation. PMID- 17868969 TI - Differential expression of peroxiredoxin 6 in fetal rat testis following in utero exposure to di(n-butyl) phthalate. AB - OBJECTIVES: To isolate and identify differentially expressed proteins in fetal rat testis following in utero exposure to di(nbutyl) phthalate (DBP). METHODS: We used the technique of proteomic analysis to compare the testis protein patterns obtained by two-dimensional gel electrophoresis from fetal rats of gestation day 19. RESULTS: We found significant differences in protein spot intensities. Subsequently several of these variant protein spots were identified by mass spectrometry. Peroxiredoxin 6 (Prdx6) was one of them. Prdx6, which expressed a higher level in DBP-treated fetal rat testes compared with normal ones, is a member of the peroxiredoxins family (Prdxs). Recently, Prdx6 had been shown to be important in protecting cells from oxidative injury. Further, immunohistochemical analyses of fetal rat testes sections were made to determine the cellular distribution of this protein, consequently a strong Prdx6 staining was found out primarily in Leydig cells. CONCLUSIONS: The present study had found several differentially regulated proteins and demonstrated the differential expression of Prdx6 in fetal rat testis following in utero exposure to DBP, when compared with controls. Combining the cellular location of Prdx6 and its function in other tissues, the results of this study could provide us with a possibility to interfere the reproductive toxicity of DBP for its specific antioxidant properties in testis tissues. PMID- 17868970 TI - Telomeric position effect: from the yeast paradigm to human pathologies? AB - Alteration of the epigenome is associated with a wide range of human diseases. Therefore, deciphering the pathways that regulate the epigenetic modulation of gene expression is a major milestone for the understanding of diverse biological mechanisms and subsequently human pathologies. Although often evoked, little is known on the implication of telomeric position effect, a silencing mechanism combining telomere architecture and classical heterochromatin features, in human cells. Nevertheless, this particular silencing mechanism has been investigated in different organisms and several ingredients are likely conserved during evolution. Subtelomeres are highly dynamic regions near the end of the chromosomes that are prone to recombination and may buffer or facilitate the spreading of silencing that emanates from the telomere. Therefore, the composition and integrity of these regions also concur to the propensity of telomeres to regulate the expression, replication and recombination of adjacent regions. Here we describe the similarities and disparities that exist among the different species at chromosome ends with regard to telomeric silencing regulation with a special accent on its implication in numerous human pathologies. PMID- 17868971 TI - Critical role of microvasculature basal lamina in ischemic brain injury. AB - Cerebral vascular system can be divided into two categories: the macrovessels and microvessels. The microvessels consist of arterioles, capillaries and venules. There are three basic components in the microvasculature: endothelial cells, basal lamina and end-feet of astrocytes. The basal lamina is situated between the endothelial cells and the end-feet of astrocytes, and connects these two layers together. Damage to the basal lamina causes the dismantlement of microvascular wall structures, which in turn results in increase of microvascular permeability, hemorrhagic transformation, brain edema and compromise of the microcirculation. The present article reviews microvascular changes during ischemic brain injury, with emphasis on basal lamina damage. PMID- 17868972 TI - Incentive motivation is associated with striatal dopamine asymmetry. AB - Dopamine plays an important role in modulating incentive motivation, expressed behaviorally as approach behavior. EEG studies report association between approach behavior and asymmetric pattern of activation in anterior cortical regions (as measured by the inverse of EEG alpha power). Therefore, individual differences in incentive motivation may reflect asymmetries in dopaminergic systems. We examined this hypothesis by studying the relationship between self reported degree of incentive motivation, and asymmetry of D2 receptor availability in healthy volunteers. Nineteen healthy participants were studied with positron emission tomography (PET) and [11C]raclopride to assess the availability of dopamine D2 receptors in left and right striatum. Incentive motivation was assessed by the Achievement scale of the Multidimensional Personality Questionnaire. The Achievement score was negatively correlated with the Asymmetry Index ([R-L]/[R+L]) of D2 receptor availability (r=-.721, p=.001), suggesting that greater positive incentive motivation is associated with higher receptor availability in the left relative to the right hemisphere. PMID- 17868973 TI - Phyllodes tumour of the breast: clinical follow-up of 33 cases of this rare disease. AB - OBJECTIVE: The "cystosarcoma phyllodes" of the breast is a rare entity which accounts for 0.5% of all breast neoplasms. The aim of our study was to analyse the clinical management with respect to patient outcome. STUDY DESIGN: The data of 5270 patients with primary breast neoplasms treated in our department between 1984 and 2005 were retrospectively analysed for the histopathologic diagnosis of a cystosarcoma phyllodes. The clinical data was analysed with respect to tumour grading and size, treatment and prognosis. RESULTS: Retrospective analysis of 5270 patients with primary breast neoplasms revealed 33 patients. In the histopathological analysis, tumour grade was classified as benign in 40%, borderline in 27% and malignant in 33% of patients. Breast conserving surgery was conducted in 58% of the patients, mastectomy in 42%. Only one patient was treated with adjuvant radiotherapy after primary surgery. Mean tumour size was 6.9 cm, and no lymph node infiltration was found in the 10 patients who received axillary lymph node dissection. Local recurrence occurred in eight patients (26%). The local recurrence rate was 50% in malignant, 20% in borderline and only 8% in benign tumours. Distant metastases were seen in three patients (9%) with malignant phyllodes tumours. Neither regarding age at primary diagnosis nor in tumour size there was a significant difference between patients with local recurrence or metastatic spread and those without (p=0.284 tumour size; p=0.739 for age; Mann-Whitney U-test). CONCLUSION: Histopathological classification appears to be the strongest prognostic factor in this disease. PMID- 17868974 TI - An approach to optimise nutrient management in environmental sanitation systems despite limited data. AB - The material flow analysis method can be used to assess the impact of environmental sanitation systems on resource consumption and environmental pollution. However, given the limited access to reliable data, application of this data-intensive method in developing countries may be difficult. This paper presents an approach allowing to develop material flow models despite limited data availability. Application of an iterative procedure is of key importance: model parameter values should first be assessed on the basis of a literature review and by eliciting expert judgement. If model outputs are not plausible, sensitive input parameters should be reassessed more accurately. Moreover, model parameters can be expressed as probability distributions and variable uncertainty estimated by using Monte Carlo simulation. The impact of environmental sanitation systems on the phosphorus load discharged into surface water in Hanoi, Vietnam, is simulated by applying the proposed approach. PMID- 17868975 TI - Surface applied water treatment residuals affect bioavailable phosphorus losses in Florida sands. AB - Water treatment residuals (WTR) can reduce runoff P loss and surface co application of P-sources and WTR is a practical way of land applying the residuals. In a rainfall simulation study, we evaluated the effects of surface co applied P-sources and an Al-WTR on runoff and leacheate bioavailable P (BAP) losses from a Florida sand. Four P-sources, namely poultry manure, Boca Raton biosolids (high water-soluble P), Pompano biosolids (moderate water-soluble P), and triple super phosphate (TSP) were surface applied at 56 and 224 kg P ha(-1) (by weight) to represent low and high soil P loads typical of P- and N-based amendments rates. The treatments further received surface applied WTR at 0 or 10 g WTR kg(-1) soil. BAP loss masses were greater in leachate (16.4-536 mg) than in runoff (0.91-46 mg), but were reduced in runoff and leachate by surface applied WTR. Masses of total BAP lost in the presence of surface applied WTR were less than approximately 75% of BAP losses in the absence of WTR. Total BAP losses from each of the organic sources applied at N-based rates were not greater than P loss from TSP applied at a P-based rate. The BAP loss at the N-based rate of moderate water-soluble P-source (Pompano biosolids) was not greater than BAP losses at the P-based rates of other organic sources tested. The hazards of excess P from applying organic P-sources at N-based rates are not greater than observed at P based rates of mineral fertilizer. Results suggest that management of the environmental P hazards associated with N-based rates of organic materials in Florida sands is possible by either applying P-sources with WTR or using a moderate water-soluble P-source. PMID- 17868976 TI - PSA in the new millennium: a powerful predictor of prostate cancer prognosis and radical prostatectomy outcomes--results from the SEARCH database. AB - OBJECTIVES: As a result of prostate-specific antigen (PSA) screening, most men today with prostate cancer present with localized disease and serum PSA values < 10 ng/ml. Within this context, it is debated whether PSA remains an important prognostic variable in more recently treated patients. We examined the prognostic significance of preoperative PSA to predict pathologic stage and biochemical progression among men undergoing radical prostatectomy in the new millennium (2000-2006). METHODS: We performed a review of 925 men with prostate cancer treated by radical prostatectomy since 2000 within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. We examined the association between preoperative PSA and risk of adverse pathologic features and biochemical progression using logistic regression and Cox proportional hazards analysis. RESULTS: After adjusting for multiple clinical preoperative characteristics, higher preoperative PSA values were associated with increased odds of extracapsular extension (p<0.001), positive surgical margins (p<0.001), and seminal vesicle invasion (p<0.001) and increased risk of biochemical progression (p=0.009). When the analyses were limited to the 690 men with a preoperative PSA<10 ng/ml and after adjusting for multiple clinical characteristics, higher preoperative PSA values remained associated with increased risk of biochemical progression (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.06-1.28, p=0.002). Even among the 448 men with a PSA<10 ng/ml and clinical stage T1c disease, preoperative PSA was associated with increased risk of biochemical progression (HR 1.14, 95%CI 1.00-1.31, p=0.047). CONCLUSIONS: PSA remains an important prognostic marker among men diagnosed with prostate cancer in the new millennium treated with radical prostatectomy and remains an important predictor of outcome even among men with preoperative PSA level < 10 ng/ml. PMID- 17868978 TI - Prostate Cancer: Are We Over-Diagnosing-or Under-Thinking? PMID- 17868980 TI - Outcomes of 24 patients with subarachnoid hemorrhage aged 80 years or older in a single center. AB - OBJECTIVE: In the developed countries, elderly population is rapidly increasing, but outcomes of elderly patients with subarachnoid hemorrhage (SAH) remain unclear. PATIENTS AND METHODS: We retrospectively reviewed the medical records of non-traumatic SAH patients aged 80 years or older, who were hospitalized in a single center between 2000 and 2005. RESULTS: There were 24 patients (80-92 years old and 83% female), representing 8.8% of all non-traumatic SAHs (n=272). Of those, six patients received an intervention (five clipping and one endovascular coiling) and the remaining 18 patients were managed conservatively. The patients who received an intervention were younger and had a better consciousness at presentation. Early mortality rate within 30 days after SAH was higher in the conservative group (61% [11/18] and 17% [1/6], p=0.155). At 6 months, mortality rate was significantly higher in the conservative group (83% [15/18] and 33% [2/6], p=0.038), and independence rate was higher in the intervention group (33% [2/6] and 0% [0/18], p=0.054). Logistic regression analysis showed that age and degree of consciousness on admission were significant predictor of outcome in 4 weeks, and that receiving intervention was significant predictor of outcome in 6 months. CONCLUSION: In elderly SAH patients with good clinical condition at presentation, an active intervention may improve the outcome. PMID- 17868981 TI - Importance of axial postcontrast images in the differential diagnosis between inflammatory and neoplastic spinal cord enlargement. PMID- 17868982 TI - Neuroimage: racemose neurocysticercosis. PMID- 17868983 TI - Up-regulation of LOX-1 expression by TNF-alpha promotes trans-endothelial migration of MDA-MB-231 breast cancer cells. AB - Adhesion of cancer cell to endothelial cells and the subsequent trans-endothelial migration are key steps in metastasis. However, the identities of the molecules mediating cancer cell/endothelial cell interaction are still not fully understood. In this study, we tested the hypothesis that lectin-like oxidized-low density lipoprotein (oxLDL) receptor-1 (LOX-1), a key mediator of vascular inflammation and atherosclerosis expressed on endothelial cell surface, mediates breast cancer cell/endothelial cell interactions. We showed that up-regulation of endothelial LOX-1 by TNF-alpha promoted the adhesion and trans-endothelial migration of MDA-MB-231 breast cancer cells. Thus, endothelial LOX-1 could present a novel pathway in breast cancer metastasis. PMID- 17868984 TI - Decomposition of toxic pollutants in landfill leachate by ozone after coagulation treatment. AB - This study deals with evaluation of organic matter from Mexico City waste sanitary landfill leachate of Bordo Poniente (including domestic and industrial) by ozonation after a coagulation treatment with Fe2(SO4)(3) (2.5 g/L at pH 4-5). The content of humic substances after the coagulation treatment decreases up to 70%. Then leachate obtained from a solid with initial COD=1511 mg/L and the pH 8.5 was treated by ozone. The aqueous samples by a UV-vis and HPLC technique were analyzed. The partial identification of the initial composition of the organic matter as well as of intermediates and final products was carried out after the extraction of the initial and ozonated leachate with benzene, chloroform:methanol (2:1) and hexane. Then the extracts with a gas chromatograph with mass detector and FID were analyzed. In the HPLC results we identify malonic and oxalic acids. The initial concentrations of these acids were 19 mg/L and 214 mg/L, respectively. The oxalic acid is formatted and accumulated in ozonation. The obtained results show that the color disappears (visually) at 100% during 5 min of ozonation. The organic substances, extracted with chloroform-methanol, may be destructed during 15 min of ozonation; the organic matter, extracted with benzene, destructs completely by ozone during 5 min, and the organic compounds extracted with hexane have a low ozonation rate. The toxic compounds presented in leachate decompose completely during 15 min of ozonation. The ozonation rate constants for each group of organics (as observed constants) were calculated applying simplified mathematical model and the recurrent least square method using the program MATLAB 6.5. PMID- 17868985 TI - Different bacterial groups for biodegradation of three- and four-ring PAHs isolated from a Hong Kong mangrove sediment. AB - Mangrove sediments have been found to degrade three- to four-ring PAHs extensively. In the present study, 11 strains from 4 genera Mycobacterium (3 strains), Sphingomonas (5), Terrabacter (2) and Rhodococcus (1) were isolated from a single surface sediment sample of a Hong Kong mangrove swamp, among which the Terrabacter strains were isolated to grow with fluoranthene for the first time. Although all four genera could degrade three- and four-ring PAHs, their in situ activities in natural sediment slurry were found to be different. A cultivable method showed that Sphingomonas strains grew rapidly under the induction of three-ring, but not four-ring PAHs, while only Mycobacterium degrading strains dominated in the four-ring PAHs spiked slurry. Culture independent method using a reverse transcriptional PCR showed expressions of nahAc-like (mainly found in Gram-negative bacteria) and nidA-like (in Gram positive bacteria) dioxygenase genes parallel with the degradation of three- and four-ring PAHs, respectively. The present study suggested that surface mangrove sediments harbored diverse PAH-degrading bacteria, which showed different importance for biodegradation of three- and four-ring PAHs in the sediment. PMID- 17868986 TI - Degradation of methylene blue: optimization of operating condition through a statistical technique and environmental estimate of the treated wastewater. AB - FeO(x)-MoO(3)-P(2)O(5) (x=1 or 1.5) composite catalyst was prepared by solid reaction method and characterized by X-ray diffraction (XRD) and X-ray Photoelectron Spectroscopy (XPS). Its catalytic activities on degradation of a heteropolyaromatic dye, methylene blue (MB), were also investigated under mild condition. In order to determine the optimum operating condition, the orthogonal experiments were devised. And the results revealed that initial concentration of MB was the key factor that affected the decoloration, while the catalysts dose has an insignificant effect. Environmental estimation was also done and the results showed that the treated wastewater have little influence on plant growth and could totally be applied to irrigation. PMID- 17868987 TI - Ammonium removal from sanitary landfill leachate using natural Gordes clinoptilolite. AB - Removal of ammonium ion (NH(4)(+)) from leachate from Odayeri sanitary landfill, located in the European part of Istanbul, was examined using Gordes (Turkish) clinoptilolite. The effects of pH, flow rate, ammonium concentration and competitive cations on the removal efficiency were investigated in both batch and column studies. Thomas model were used to analyze the breakthrough data. Nonlinear least square method was applied for fitting the column data. The competitive effect was observed more effective in lower ammonium concentration and higher cation concentrations. Conditioning and regeneration using NaCl improved removal efficiency of ammonium from leachate. PMID- 17868988 TI - Prediction of biosorption efficiency for the removal of copper(II) using artificial neural networks. AB - Various low-cost adsorbents have been used for removing Cu(II) ions from aqueous solutions for the treatment of copper containing wastewaters to remove organic compounds and color. Sawdust is an impressive adsorbent in terms of adsorption efficiency, cost and availability; hence the use of sawdust as biosorbent has been widely studied. Many earlier investigations tried to correlate the experimental data with available models or some modified empirical equations, but these results were unable to predict the values of parameters from a single equation. Artificial neural networks (ANN) are effective in modeling and simulation of highly non-liner multivariable relationships. A well-designed and very well trained network can converge even on multiple number of variables at a time without any complex modeling and empirical calculations. In this present work ANN is applied for the prediction of percentage adsorption efficiency for the removal of Cu(II) ions from aqueous solutions by sawdust. Artificial neural network model, based on multilayered partial recurrent back-propagation algorithm has been used. The performance of the network for predicting the sorption efficiency of sawdust for copper is found to be very impressive. PMID- 17868989 TI - Three modified activated carbons by different ligands for the solid phase extraction of copper and lead. AB - In the presented work, 5,5-diphenylimidazolidine-2,4-dione (phenytoin) (DFTD), 5,5-diphenylimidazolidine-2-thione-,4-one (thiophenytoin) (DFID) and 2-(4' methoxy-benzylidenimine) thiophenole (MBIP) modified activated carbons have been used for the solid phase extraction of copper and lead ions prior to their flame atomic absorption spectrometric determinations. The influences of the various analytical parameters including pH, amounts of reagent, sample volume and eluent type, etc. on the recovery efficiencies of copper and lead ions were investigated. The influences of alkaline, earth alkaline and some transition metals on the adsorption of the analytes were also examined. The detection limits by three sigma for analyte ions were 0.65 and 0.42 microg L(-1) using activated carbon modified with DFID; 0.52 and 0.37 microg L(-1) using activated carbon modified with DFTD and 0.46 and 0.31 microg L(-1) using activated carbon modified with MBIP for Pb(II) and Cu(II), respectively. The procedure was applied to the determination of analytes in natural waters, soil, and blood samples with satisfactory results (recoveries greater than 95%, R.S.D.'s lower than 4%). PMID- 17868990 TI - Analysis of CO2 separation and simulation of a partially wetted hollow fiber membrane contactor. AB - A steady state model was developed for a microporous hollow fiber membrane contactor operated under partially wetted conditions accompanied by chemical reactions, to analyze CO2 absorption into the aqueous solution of diethanolamine (DEA). The proposed diffusion-reaction model contains reversible chemical reactions in the liquid bulk as well as wetted parts of the membrane pores. A numerical scheme was employed to solve the simultaneous nonlinear mathematical expressions, and the results were validated with experimental data in the literature. The gas phase concentration and velocity profile in axial direction inside the shell, liquid concentration profile in axial and radial directions inside the fibers, and also those within the wetted parts of the pores were predicted by using the model. The results of the model and proposed numerical scheme show that membrane wetting, even in very low fractions, can decrease the absorption flux significantly. The wetting fraction of membrane was predicted both with and without consideration of chemical reactions inside the wetted pores. The results indicate that the chemical reactions inside the wetted pores, which have been disregarded in the literature, have considerable effects on the prediction of membrane wetting fraction. PMID- 17868991 TI - Immobilization of aqueous cadmium by addition of phosphates. AB - In situ immobilization of heavy metals in polluted soils using phosphates leads to formation of products which are highly insoluble and thermodynamically stable over a broad pH and Eh range. In this research effectivity of Cd ions immobilization (initial [Cdaq]-4.800 mM) from aqueous solutions by different phosphorus compounds (K2HPO4, NH4H2PO4 and "Polifoska 15" fertilizer) was compared at pH in the range 4.00-9.00 and for reaction times 2-1440 h. The highest reduction of cadmium concentration (>99%), owing due to the formation of cadmium phosphates, was observed for all used phosphorus sources within pH range of 6.75-9.00. Uptake of cadmium for pH< or =5.00 did not exceed 80% and was lowest in the reaction with "Polifoska 15" fertilizer (28.25%). Identification of phases formed in the reactions using XRD, FTIR and SEM-EDS-EBSD was carried out. It was noticed that crystallinity of formed solid decreased with pH increase. Formation of Cd5H2(PO4)4.4H2O was observed in acidic conditions (pH< or =5.00), at pH approximately 7.00 mixture of following cadmium phosphates Cd(H2PO4)2, Cd3(PO4)2 and Cd5H2(PO4)4.4H2O was formed. Amorphic cadmium phosphates were noticed in alkaline conditions (pH>8.50). PMID- 17868992 TI - Desorption and re-adsorption of carbon nanotubes: comparisons of sodium hydroxide and microwave irradiation processes. AB - This study evaluates exhausted carbon nanotubes regenerated by desorption processes using 1mM NaOH and microwave irradiation processes. Kinetic analyses of re-adsorption were performed using pseudo first- and second-order models. Regression results revealed that a pseudo first-order model accurately captured re-adsorption kinetics. The regeneration efficiency was 28, 30, 35 and 44% at 18, 28, 38 and 48 degrees C using desorption agent of 1mM NaOH for 24h, respectively. Microwave power was considered the most important factor in regeneration experiments, as the temperature reached by exhausted CNTs was directly related to microwave power in this study. Additionally, microwave regeneration was more effective than the desorption agent of NaOH. The most effective conditions for regenerating exhausted CNTs were a microwave power input of 1000 W for 20 min. PMID- 17868993 TI - IGF-1 exacerbates the neurotoxicity of the mitochondrial inhibitor 3NP in rats. AB - Insulin-like Growth Factor 1 (IGF-1) has broad-range neuroprotective effects and is a therapeutic candidate for Huntington's disease (HD). IGF-1 protects striatal neurons from the toxicity of mutated huntingtin in vitro and improves neuronal survival in vivo in a phenotypic model of HD involving excitotoxic cell death. Because HD is a multifactorial disease, it is important to evaluate the neuroprotective role of IGF-1 in other pathological situations involved in HD progression. We have evaluated the neuroprotective effects of IGF-1 in vivo, using the 3-nitropropionic acid (3NP) rat model which replicates the mitochondrial dysfunction observed in HD. Continuous intracerebroventricular infusion of recombinant IGF-1 at a low dose (0.025 microg/h for 5 days) did not alleviate motor impairment and weight loss induced by 3NP treatment. In addition, histological evaluation and quantification of DNA fragmentation evidenced no improvement in neuronal survival. Of interest, we found that a higher concentration of IGF-1 (0.25 microg/h) resulted in an exacerbation of 3NP toxicity on striatal neurons. These results suggest that intracerebral delivery of IGF-1 may not provide a fully effective therapeutic strategy for HD or other disorders involving mitochondrial impairment. PMID- 17868994 TI - Effect of different patterns of low-frequency stimulation on piriform cortex kindled seizures. AB - Low-frequency stimulation (LFS) is an antiepileptic and antiepileptogenic electrical stimulation. In this study the effect of changes in some LFS (1Hz, monophasic square wave) parameters (intensity, pulse duration and train duration) on piriform cortex kindled seizures was investigated both in fully kindled rats and during kindling acquisition. In fully kindled animals, application of different patterns of LFS immediately before kindling stimulation had no significant effect on seizure parameters. However, daily (15 min) application of LFS (0.1 ms pulse duration at intensity equal to after-discharge threshold (ADT) and 1 ms pulse duration at intensity equal to 1/4 ADT) during inter-seizure interval of 7 days significantly reduced the stage 5 duration of the next kindled seizure. Application of the same two LFS protocols for 3 days and 2 weeks had no effect on seizure parameters. The effect of LFS was also tested using different paradigms during kindling acquisition. When LFS (0.1 and 1 ms pulse duration, intensity equal to ADT and 1/4 ADT) was delivered daily after each kindling stimulation, it could significantly decrease after-discharge duration in various days during kindling development. In this experiment, only LFS with 0.1 ms pulse duration and intensity equal to ADT significantly delayed the appearance of seizure stages 1 and 2. According to obtained results, it may be concluded that in fully kindled rats application of different patterns of LFS before kindling stimulation has no anticonvulsant effect, but it can exert an inhibitory effect when applied during an inter-seizure interval of 7 days. In addition, LFS has antiepileptogenic effect during kindling acquisition. These effects depend on the applied LFS parameters (e.g. intensity, pulse duration and train duration). PMID- 17868995 TI - In situ hybridization histochemical and immunohistochemical evidence that striatal projection neurons co-containing substance P and enkephalin are overrepresented in the striosomal compartment of striatum in rats. AB - In a prior study, we showed that the few striatal projection neurons that contain both substance P (SP) and enkephalin (ENK) in rats may preferentially project to the substantia nigra pars compacta. Since striatal neurons that project to the pars compacta are thought to preferentially reside in the striosomal compartment, we investigated if striatal neurons that contain both SP and ENK are preferentially localized to the patch compartment. We used in situ hybridization histochemistry to double-label sections for SP and ENK to identify SP/ENK co containing neurons, and immunolabeling of adjacent sections for the mu opiate receptor (MOR) to define the striosomal compartment. We found that 32.3% of neurons containing both SP and ENK were localized to the striosomal compartment, which itself only made up 12.8% of the striatum. Our results further showed that the density of neurons co-containing SP and ENK was three-fold higher in striosomes than in the matrix compartment. These results are consistent with the notion that SP/ENK colocalizing neurons preferentially project to pars compacta, and these and our prior results additionally raise the possibility that neurons of this type in the striatal matrix may also project to the pars compacta. PMID- 17868996 TI - Copolymer-1 (Cop-1) improves neurological recovery after middle cerebral artery occlusion in rats. AB - The damage in ischemic stroke is caused by two events: (i) the ischemic phenomenon by itself; (ii) the self-destructive mechanisms developed as a consequence of ischemia. The inflammatory response is one of these destructive phenomena that accompanies and exacerbates the developing injury. Since it has been suggested that immune cells participate in neuroprotective and restorative processes, modulation rather than elimination of this inflammatory response could be a strategy to improve the neurological outcome. The immune modulator copolymer 1 (Cop-1), a synthetic basic random copolymer of amino acids, is a potent inducer of Th2 regulatory cells which, aside from exerting modulatory actions, is capable of releasing neurotrophic factors. There is evidence that Cop-1-specific T cells exert neuroprotective and even restorative effects in diverse neurodegenerative diseases. In order to test the ability of Cop-1 to prevent ischemic injury in a model of transient middle cerebral artery (MCA) occlusion, two groups of rats were treated either with Cop-1 or with saline solution (SS). Seven days after occlusion, Cop-1 treated rats presented a significant improvement in neurological function compared to SS-treated animals (1.2+/-0.4 and 2.8+/-0.5 mean+/-S.D., respectively; p=0.008). Histological findings showed that the percentage of infarct volume was smaller in Cop-1 treated rats (4.8+/-1.5), in comparison with those receiving SS (32.2+/-8.6; p=0.004). Cop-1 constitutes a promising therapy for stroke; thereby, the enforcement of further experimental investigation is encouraged in order to be able to formulate the best strategy. PMID- 17868998 TI - Fecal and serological survey of Neospora caninum in farm dogs in Costa Rica. AB - To detect oocysts of Neospora caninum in dog feces and to determine the excretion pattern in dogs from specialized dairy farms in Costa Rica, a total of 265 fecal samples from 34 dogs were collected at intervals from February to August 2005. Fecal samples were examined for N. caninum-like oocysts microscopically, by DNA detection using the polymerase chain reaction (PCR), and by bioassay. N. caninum DNA was detected by PCR in four fecal samples, twice from one dog, but oocysts were not detected microscopically in these dogs. Sera of 31 of 34 dogs were tested for antibodies to N. caninum by a competitive-inhibition ELISA (VMRD). Fifteen (48.4%) of 31 dogs had antibodies to N. caninum by ELISA. Seroconversion was not found in 28 dogs that were bled twice, 4 months apart (March and July 2005). Only one dog tested positive to N. caninum by both ELISA and PCR. This is the first report of finding N. caninum DNA in feces of naturally infected dogs in Costa Rican dairy farms. PMID- 17868999 TI - Neural stem cells, tumour stem cells and brain tumours: dangerous relationships? AB - Neural stem cells (NSC) have been implicated not only in brain development and neurogenesis but also in tumourigenesis. Brain tumour stem cells (BTSC) have been isolated from several paediatric or adult human brain tumours, however their origin is still disputed. This review discusses the normal role of NSC in the adult mammalian brain and their anatomical location. It compares the molecular characteristics and the biological behaviour of NSC/BTSC, and describes the molecular pathways involved in controlling self-renewal and maintenance of adult NSC/BTSC and brain tumour development. It also assesses the current hypotheses about the origin of BTSC and the clinical consequences. PMID- 17869000 TI - Isolation and culture of different epidermal and dermal cell types from human scalp suitable for the development of a therapeutical cell spray. AB - BACKGROUND: Previous studies demonstrated, that cultured epithelial autografts (CEA) can be isolated and skin cell sprays can be produced for application on different types of wounds. The purpose of the present study was to determine which cell types can be isolated from the human scalp and whether these cells can be used for spray transplantation. METHODS: Outer root sheath cells (ORS), keratinocytes, melanocytes, dermal papilla cells (DP), and dermal sheath cells (DSC) were isolated from human scalp tissue. Isolated cells were characterized, expanded and sprayed in an in vitro model. Growth behaviour, morphology and cell counts were compared with non-sprayed cells. RESULTS: With acceptable time, equipment and laboratory personnel a sufficient amount of keratinocytes, ORS, melanocytes, DP cells and DSC cells could be achieved. The cells are sufficient for application as a cell spray. Cells, positive for Integrin alpha6, Cytokeratin 19, CD73 and CD105 were identified within the cultures. CONCLUSIONS: Human scalp is suitable to gain epidermal and dermal cells for the development of therapeutic cell spray transplantation. Further studies have to determine, whether these cells can be combined to produce wound specific skin substitutes. PMID- 17869001 TI - The use of eidronate disodium in the prevention of heterotopic ossification in burn patients. AB - Heterotopic ossification (HO) is a well-known complication of moderate and severe burn injuries. The development and progression of HO in burn patients are poorly understood phenomena at this time. Numerous measures aimed at preventing or minimizing HO have been described, but no definitive prophylactic modality has been found. Biphosphonate compounds are known to inhibit calcification, but previous studies are equivocal regarding their effectiveness in preventing HO in burn patients. We retrospectively reviewed the effect of etidronate disodium (EDHP), a bisphosphonate, on the development of HO in severely burned patients. We found that not only was EDHP ineffective in preventing HO, the group of patients treated with EDHP demonstrated an increased incidence of HO over that seen in a comparison group. This was true after controlling for age, sex, and %TBSA burned. Based on the results of this study, the routine use of etidronate disodium to prevent HO in burn patients cannot be recommended. PMID- 17869002 TI - Five years' experience of the modified Meek technique in the management of extensive burns. AB - BACKGROUND: The Meek technique of skin expansion is useful for covering a large open wound with a small piece of skin graft, but requires a carefully followed protocol. METHODS: Over the past 5 years, a skin graft expansion technique following the Meek principle was used to treat 37 individuals who had sustained third degree burns involving more than 40% of the body surface. A scheme was devised whereby the body was divided into six areas, in order to clarify the optimal order of wound debridements and skin grafting procedures as well as the regimen of aftercare. RESULTS: The mean body surface involvement was 72.9% and the mean area of third degree burns was 41%. The average number of operations required was 1.84. There were four deaths among in this group of patients. CONCLUSIONS: The Meek technique of skin expansion and the suggested protocol are together efficient and effective in covering an open wound, particularly where there is a paucity of skin graft donor sites. PMID- 17869003 TI - Social and economic factors associated with the risk of burn injury. AB - Socioeconomic status (SES) factors have been associated with the risk of burn, but the relative significance of these findings across populations and cultures is not known. The purpose of this literature synthesis was to determine: (1) which SES factors have been associated with burn risk; (2) whether these factors are generalizable across studies; and (3) which of these factors are modifiable. A search of studies of SES and burn risk published between January 1992 and September 2006 yielded 34 pertinent studies. SES risk factors were placed into categories pertaining to ethnicity, income, family structure, education, occupation, residence, and general SES. SES factors associated with increased risk included: ethnicity (non-white), low income, large families, single parents, illiteracy, low maternal education, unemployment, job loss, substandard living conditions, not owning a home, not having a telephone, and crowding. The lack of standard definitions for SES, as well as the heterogeneity of study populations and outcome variables, limits the generalizability of these results. However, the results confirm that several SES factors are associated with increased risk of burn and provide a template of factors to be considered when studying burn populations. PMID- 17869005 TI - Cross-modal integration of intranasal stimuli: a functional magnetic resonance imaging study. AB - Most odorants, in addition to the olfactory system, also activate the intranasal trigeminal system. Recent studies have shown that pure trigeminal stimulation activates somatosensory regions as well as regions traditionally thought of as primary olfactory areas. As a main aim of this study we wished to a) ascertain which brain regions are responsive to an "artificially" bimodal odor composed of a trigeminal (CO(2)) and an olfactory stimulant (phenyl ethyl alcohol, PEA) and b) determine if presenting CO(2) and PEA simultaneously activates different brain regions than when presenting them individually. Fifteen men were scanned using functional magnetic resonance imaging while smelling PEA, CO(2), and a mixture of both stimuli (CO(2)PEA) presented simultaneously. Odors were presented monorhinally to the right nostril in a block design. The contrast between CO(2)PEA and baseline revealed areas implicated in the processing of both olfactory and trigeminal stimuli. When the mixture was contrasted with the sum of its single components (CO(2)PEA-{CO(2)+PEA}), activations in integration centers (left superior temporal and right intraparietal sulcus) and in orbitofrontal areas (left medial and lateral orbitofrontal cortex) were detected. The opposite contrast ({CO(2)+PEA}-CO(2)PEA) did not reveal any significant activation. In contrast to studies which have used natural mixed olfactory/trigeminal stimuli, we have shown that the perception of an artificial mixed olfactory/trigeminal stimulus activates, as opposed to inhibiting the olfactory cortex. Further, we also conclude that a mixed olfactory/trigeminal stimulus appears to lead to higher cortical activations than the sum of its parts. PMID- 17869006 TI - P2 receptor expression in the dopaminergic system of the rat brain during development. AB - Extracellular ATP facilitates the release of dopamine via P2 receptor activation in parts of the mesolimbic system. To characterize P2X/Y receptor subtypes in the developing dopaminergic system, their expression in organotypic slice co-cultures including the ventral tegmental area/substantia nigra (VTA/SN) complex and the prefrontal cortex (PFC) was studied in comparison to the receptor expression in 3 5 day-old and adult rats. Reverse transcriptase-polymerase chain reaction (RT PCR) with specific primers for the P2X(1,2,3,4,6,7) and P2Y(1) receptors in the tissue extracts of organotypic co-cultures revealed the presence of the P2X and P2Y receptor mRNAs investigated. Multiple immunofluorescence labeling of the P2X/Y receptor protein indicated differences in the regional expression in the organotypic co-cultures after 10 days of cultivation (VTA/SN, P2X(1,2,3,4,6,7), P2Y(1,6,12); PFC, P2X(1,3,4,6,7), P2Y(1,2,4,6,12)). At postnatal days 3-5, an immunofluorescence mostly comparable to that of adult rats was observed (VTA/SN and PFC: P2X(1,2,3,4,6,7), P2Y(1,2,4,6,12)). There was one important exception: the P2X(7) receptor immunocytochemistry was not found in adult tissue, suggesting a potential role of this receptor in the development. Only few P2 receptors (e.g. P2X(1), P2Y(1)) were expressed at fibers interconnecting the dopaminergic VTA/SN with the PFC in the organotypic co-cultures. The treatment of the cultures with the ATP analogues 2-methylthio-ATP and alpha,beta-methylene-ATP induced an increase in axonal outgrowth and fiber density, which could be inhibited by pre treatment with the P2X/Y receptor antagonist pyridoxal-phosphate-6-azophenyl 2',4'-disulphonic acid. The co-localization of the dopamine-(D1) receptor with the P2X(1) receptor in organotypic slice cultures was evident. In the PFC of the co-cultures, and that of young but not adult rats, a number of tyrosine hydroxylase (TH)-positive cells also possessed P2Y(1)-immunoreactivity (IR). Additionally, a strong P2Y(1)-IR was observed on astrocytes. The present results show a time-, region- and cell type-dependent in vitro and in vivo expression pattern of different P2 receptor subtypes in the dopaminergic system indicating the involvement of ATP and its receptors in neuronal development and growth. PMID- 17869008 TI - Reproductive experience alters hippocampal neurogenesis during the postpartum period in the dam. AB - Pregnancy and the postpartum period are a time of maximal neural and behavioral plasticity. Recent work has shown that hippocampus-dependent learning and memory performance and hippocampus morphology are affected by motherhood and reproductive experience (number of times pregnant and given birth). Adult neurogenesis in the dentate gyrus of the hippocampus is influenced by steroid hormones such as estradiol and corticosterone, which fluctuate during pregnancy and the postpartum period. Thus, it is possible that hippocampal neurogenesis may be affected by motherhood and reproductive experience. The present study aimed to investigate the role of reproductive experience on hippocampal neurogenesis via cell proliferation and cell survival and to determine whether differences were due to the effect of pregnancy and/or pup-exposure alone. Four groups of female Sprague-Dawley rats were used; multiparous, primiparous, nulliparous, and nulliparous rats exposed to pups. All rats were injected with 5-bromo-2 deoxyuridine (BrdU) (200 mg/kg) approximately 24 h after birth/pup-exposure with age-matched controls. Rats were perfused either 24 h (Expt. 1: Cell proliferation) or 21 days (Expt. 2: Cell survival) after BrdU injection. Results show there is a significant decrease in cell proliferation in the dentate gyrus of primiparous and multiparous rats during the early postpartum period, and a decrease in cell survival in the dentate gyrus during the postpartum in primiparous rats, regardless of pup-exposure, compared with all other groups. In addition, brief pup exposure to nulliparous rats significantly increased cell proliferation and cell death in the dentate gyrus, while 22 days of pup exposure to nulliparous rats (sensitized rats) resulted in increased cell survival and cell death in the dentate gyrus. Collectively these results indicate that reproductive experience significantly affects hippocampal neurogenesis and that these effects are not due to the effect of pregnancy or pup-exposure alone. PMID- 17869007 TI - Ginkgo biloba extract EGb 761 attenuates hippocampal neuronal loss and cognitive dysfunction resulting from chronic restraint stress in ovariectomized rats. AB - We have recently found that a combination of ovariectomy (OVX) and chronic restraint stress causes cognitive dysfunction and reduces hippocampal CA3 neurons in female rats and that estrogen replacement suppresses the OVX/stress-induced behavioral and morphological changes. In this study, we examined the effect of Ginkgo biloba extract (EGb 761), a popular herbal supplement, on the cognitive dysfunction and neuromorphological change in OVX/stress-subjected rats. Female Fisher 344 rats were randomly divided into three groups: vehicle-treated OVX, EGb 761 (50 mg/kg) -treated OVX and vehicle-treated sham-operated control groups. Two months after ovariectomy, all animals received restraint stress for 21 days (6 h/day), and were then subjected to a novel object recognition test followed by morphological examination by Nissl staining. EGb 761 was orally administered once daily until the behavioral analysis was done. Treatment with EGb 761 improved memory impairment and neuronal loss of hippocampus in the OVX/stress-subjected group in the same ways as 17beta-estradiol. On the other hand, EGb 761 did not affect the loss of bone mineral density and increase in body weight after OVX, although 17beta-estradiol attenuated them. These results have important implications for neuroprotective and cognition enhancing effects of EGb 761 in postmenopausal women and suggest that the effects are mediated by a different mechanism from estrogen. PMID- 17869009 TI - KLF4: a novel target for the treatment of atherosclerosis. AB - Atherosclerosis is an inflammatory disease characterized by a large amount of hyperproliferation and poorly differentiated or undifferentiated smooth muscle cells in atherosclerotic plaque. Cancer cells differ from normal cells in many aspects, including hyperproliferation and loss of differentiation. So the research on tumor may shed light on the treatment of atherosclerosis. Given that Kruppel-like factor 4 (KLF4) has an important function in tumor development and progression, it may be associated with the formation and development of atherosclerosis. Recently, KLF4 expression has been documented in vascular endothelial cells. KLF4, which is normally not expressed in differentiated SMC in vivo, was rapidly up-regulated in response to vascular injury. In addition, KLF4 is a critical regulator in macrophage activation. Endothelial dysfunction, macrophage activation and VSMC phenotype switching are critical component elements in development of atherosclerosis. Herein we hypothesize that KLF4 is an important regulator in different phase of atherosclerosis and may be a novel target of prevention and cure of atherosclerosis. Further investigation is needed to approach the concrete signaling pathways about KLF4. PMID- 17869010 TI - Endothelial progenitor cells as cellular vehicles to deliver oncolytic virus therapies to metastatic tumors: the "Trojan horse" approach. AB - In view of the limited success of available treatment modalities for metastatic tumor, alternative and complementary strategies need to be developed. Oncolytic viruses are capable of selective replication in malignant cells and therefore offer levels of potency and specificity that are potentially far higher than conventional treatments for tumor. However, lack of systemic delivery technique for therapeutic viruses impacts their application in treating patients with multiple disseminated metastases. Recent studies have demonstrated that when being transplanted, endothelial progenitor cells can migrate via peripheral blood and home exclusively to the site of tumor neovasculature. We hypothesized that endothelial progenitor cells can act as "Trojan horse" to systemically deliver oncolytic virus to metastases in order to inhibit tumor neovascularization formation and eventually eradicate the metastatic tumor. PMID- 17869011 TI - Placental pathology may cause schizophrenia. PMID- 17869012 TI - Contribution of TIA-1+ and granzyme B+ cytotoxic T lymphocytes to cryptal apoptosis and ulceration in active inflammatory bowel disease. AB - In spite of the clinicopathological differences between Crohn's disease (CD) and ulcerative colitis (UC), they share the fundamental feature of destructive inflammatory processes involving the intestinal wall. The aim of the present study was to investigate the contribution of cell-mediated cytotoxicity to mucosal damage in CD and UC. Colonic mucosal biopsy specimens from patients with active CD (n=25) and UC (n=26) and normal controls (n=12) were immunohistochemically analyzed for the expression of CD3, CD4, CD8, and T cell restricted intracellular antigen (TIA)-1, which promotes apoptosis by alternative splicing of pre-messenger RNA of the Fas receptor, and granzyme B (GrB), which leads to apoptosis through induction of perforin. Histological scores for cryptal apoptosis and ulceration were assessed in hematoxylin- and eosin-stained sections. In patients with CD and UC, CD3+(P<0.001), CD4+(P<0.001), CD8+(P<0.01), TIA-1+(CD, P<0.01; UC, P<0.001), and GrB+(CD, P<0.01; UC, P<0.001) intraepithelial lymphocytes (IELs) were significantly increased as compared with controls. Positive relationships were found between the histological scores for apoptosis or ulceration and the numbers of CD8+or TIA-1+IELs. In conclusion, cytotoxic T lymphocytes are present in increased numbers in the mucosa of patients with active CD and UC, and local activation of IELs may contribute to mucosal damage with these diseases. PMID- 17869013 TI - Effect of tumor bulk on local control and survival of patients with T1 glottic cancer: a 30-year experience. AB - PURPOSE: To evaluate the effect of tumor bulk on local control and survival of patients with T1 glottic cancer. METHODS AND MATERIALS: Effects of tumor bulk, T stage, anterior-commissure involvement, treatment duration, and fraction size were analyzed in 208 patients; 136 had small tumors and 72 had bulky tumors. Anterior-commissure was involved in 54 patients. Treatment duration ranged from 39 to 64 days and fraction size ranged from 1.8 to 2.0 Gy. Median follow-up was 5.1 years. RESULTS: Five-year actuarial local control rates were 86.1% and 91.4% after radiotherapy and salvage laryngectomy. On univariate analysis, local control rates were 92.6% and 73.6% for small and bulky tumors (p = 0.03), 89.6% and 75.9% for patients without and with anterior-commissure involvement (p = 0.01), 92.6% and 75.6% when treatment duration was 50 days (p = 0.04), and 90.2% and 76.4% with 2 Gy and 1.8 Gy (p = 0.02) per fraction. On multivariate analysis, tumor bulk was the only significant factor that affected local control (p = 0.007). Ultimate local control rates after salvage were 97.1% and 80.5% for patients with small and bulky tumors. Disease-free survival rates at 5 years for small and bulky tumors were 96.3% and 84.7% (p = 0.001). Median duration to recurrence for small tumors was 30 months as compared with 11 months for bulky tumors. CONCLUSION: Tumor bulk is a highly significant prognostic factor for radiation control of T1 glottic cancer. Patients with bulky tumors had lower local control and disease-free survival rates and shorter duration to recurrence than those with small tumors. PMID- 17869014 TI - Salvage hypofractionated radiotherapy for biochemically recurrent prostate cancer after radical prostatectomy. AB - PURPOSE: To evaluate whether hypofractionation is well tolerated and to preliminarily assess biochemical control of this regimen in a postprostatectomy, salvage setting. METHODS AND MATERIALS: A retrospective analysis was performed in 50 patients treated between May 2003 and December 2005 with hypofractionated radiotherapy for biochemical recurrence after radical prostatectomy. Radiotherapy was prescribed to the prostatic fossa to 65-70 Gy in 26-28 fractions of 2.5 Gy each, using intensity-modulated radiotherapy with daily image localization. Toxicities were scored using a modified Radiation Therapy Oncology Group scale and the Fox Chase modification of Late Effects Normal Tissue scale. The median follow-up was 18.9 months (range, 5.3-35.9). RESULTS: No Grade 3 or greater acute or late toxicities were observed. Grade 2 toxicities included four acute genitourinary, one acute gastrointestinal, two late genitourinary, and two late gastrointestinal toxicities. Of the 50 patients, 39 demonstrated a continuous biochemical response after salvage therapy, 3 had an initial response before prostate-specific antigen failure, and 7 had prostate-specific antigen progression, 1 of whom died of progressive metastatic disease. Finally, 1 patient discontinued therapy because of the diagnosis of a metachronous pancreatic cancer and died without additional prostate cancer follow-up. All remaining patients were alive at the last follow-up visit. A lower presalvage prostate-specific antigen level was the only significant prognostic factor for improved biochemical control. The estimated actuarial biochemical control rate at 2 years was 72.9%. CONCLUSIONS: The toxicity and early biochemical response rates were consistent with expectations from conventional fractionation. Additional follow-up is required to better document the biochemical control, but these results suggest that hypofractionation is a well-tolerated approach for salvage radiotherapy. PMID- 17869015 TI - Temporal change in brain natriuretic Peptide after radiotherapy for thoracic esophageal cancer. AB - PURPOSE: To investigate the relationships of plasma levels of brain natriuretic peptide (BNP) with abnormal (18)F-fluorodeoxyglucose (FDG) accumulation in the myocardium corresponding to irradiated fields and temporal changes in BNP, which is used as an index of heart remodeling, after radiotherapy for the mediastinum. MATERIALS AND METHODS: Brain natriuretic peptide concentrations were measured before and after radiotherapy for thoracic esophageal cancer, and the change in BNP concentration after radiotherapy was investigated. Moreover, FDG accumulation in the myocardium was investigated in patients who had undergone FDG positron emission tomography less than 14 days before or after measurement of BNP concentration, and the Mann-Whitney U test was used to detect significant difference between BNP concentrations in patients with and without abnormal FDG accumulation corresponding to the irradiated field. RESULTS: There was significant difference between the levels of BNP in patients without abnormal FDG accumulation in the irradiated myocardium and in patients with abnormal FDG accumulation (p < 0.001). The levels of BNP in the 9-24 months after radiotherapy group and in the >24 months after radiotherapy group were significantly higher than the levels in the before radiotherapy group, immediately after radiotherapy group, 1-2 months after radiotherapy group, and control group. CONCLUSIONS: The level of BNP was significantly increased more than 9 months after the start of radiotherapy and was significantly higher in patients who had high FDG accumulation corresponding to the irradiated field. The results of this study indicate that BNP concentration might be an early indicator of radiation-induced myocardial damage. PMID- 17869016 TI - Shrinkage of locally advanced non-small-cell lung cancers in response to induction chemotherapy: implications for radiotherapy treatment planning. AB - PURPOSE: To quantify the impact that changes in tumor volume after induction chemotherapy have on radiotherapy treatment planning for locally advanced non small-cell lung cancer. METHODS AND MATERIALS: An analysis of coregistered pre- and postchemotherapy tumor volumes in a Phase II study of induction chemotherapy delivered before radical radiotherapy. RESULTS: Using the Response Evaluation Criteria In Solid Tumors measurement, 35% of patients had a partial response and 62% had stable disease after chemotherapy. Conversely, volumetric decreases in tumor size were seen in 95% of patients. Mean decreases in gross tumor volume and planning target volume were 37% and 26%, respectively. Using the smaller postchemotherapy tumor volume to plan radiotherapy treatment leads to a mean decrease in volume of lung receiving 20 Gy or greater of 3% (p < 0.005). Targeting the postchemotherapy volume also results in the delivery of a significant, although inhomogeneous, incidental dose of radiation to the rind of tissue formed around the shrinking tumor. Disease shrinkage is anisotropic, with greater displacements observed along anterior, posterior, and lateral margins. After chemotherapy, there is measurable blurring of the tumor's radiologic edge. CONCLUSIONS: Modest decreases in tumor volume that are not reflected by the Response Evaluation Criteria In Solid Tumors measurement occur in most patients. Although targeting the postchemotherapy tumor may decrease lung toxicity, the magnitude of the benefit is small. Because this strategy runs the risk of increasing the marginal recurrence rate, it should be used with caution. Quantification of tumor shrinkage and margin blurring permits more accurate reconstruction of the prechemotherapy target volume. PMID- 17869017 TI - Increasing tumor volume is predictive of poor overall and progression-free survival: secondary analysis of the Radiation Therapy Oncology Group 93-11 phase I-II radiation dose-escalation study in patients with inoperable non-small-cell lung cancer. AB - PURPOSE: Patients with non-small-cell lung cancer (NSCLC) in the Radiation Therapy Oncology Group (RTOG) 93-11 trial received radiation doses of 70.9, 77.4, 83.8, or 90.3 Gy. The locoregional control and survival rates were similar among the various dose levels. We investigated the effect of the gross tumor volume (GTV) on the outcome. METHODS AND MATERIALS: The GTV was defined as the sum of the volumes of the primary tumor and involved lymph nodes. The tumor response, median survival time (MST), and progression-free survival (PFS) were analyzed separately for smaller (< or =45 cm(3)) vs. larger (>45 cm(3)) tumors. RESULTS: The distribution of the GTV was as follows: < or =45 cm(3) in 79 (49%) and >45 cm(3) in 82 (51%) of 161 patients. The median GTV was 47.3 cm(3). N0 status and female gender were associated with better tumor responses. Patients with smaller (< or =45 cm(3)) tumors achieved a longer MST and better PFS than did patients with larger (>45 cm(3)) tumors (29.7 vs. 13.3 months, p < 0.0001; and 15.8 vs. 8.3 months, p < 0.0001, respectively). Increasing the radiation dose had no effect on the MST or PFS. On multivariate analysis, only a smaller GTV was a significant prognostic factor for improved MST and PFS (hazard ratio [HR], 2.12, p = 0.0002; and HR, 2.0, p = 0.0002, respectively). The GTV as a continuous variable was also significantly associated with the MST and PFS (HR, 1.59, p < 0.0001; and HR, 1.39, p < 0.0001, respectively). CONCLUSIONS: Radiation dose escalation up to 90.3 Gy did not result in improved MST or PFS. The tumor responses were greater in node-negative patients and women. An increasing GTV was strongly associated with decreased MST and PFS. Future radiotherapy trials patients might need to use stratification by tumor volume. PMID- 17869018 TI - Protection of salivary function by concomitant pilocarpine during radiotherapy: a double-blind, randomized, placebo-controlled study. AB - PURPOSE: To investigate the effect of concomitant administration of pilocarpine during radiotherapy for head-and-neck squamous cell carcinoma (HNSCC) on postradiotherapy xerostomia. METHODS AND MATERIALS: A prospective, double blind, placebo-controlled randomized trial including 170 patients with HNSCC was executed to study the protective effect of pilocarpine on radiotherapy-induced parotid gland dysfunction. The primary objective endpoint was parotid flow rate complication probability (PFCP) scored 6 weeks, 6 months, and 12 months after radiotherapy. Secondary endpoints included Late Effects of Normal Tissue/Somatic Objective Management Analytic scale (LENT SOMA) and patient-rated xerostomia scores. For all parotid glands, dose-volume histograms were assessed because the dose distribution in the parotid glands is considered the most important prognostic factor with regard to radiation-induced salivary dysfunction. RESULTS: Although no significant differences in PFCP were found for the two treatments arms, a significant (p = 0.03) reduced loss of parotid flow 1 year after radiotherapy was observed in those patients who received pilocarpine and a mean parotid dose above 40 Gy. The LENT SOMA and patient-rated xerostomia scores showed similar trends toward less dryness-related complaints for the pilocarpine group. CONCLUSIONS: Concomitant administration of pilocarpine during radiotherapy did not improve the PFCP or LENT SOMA and patient-rated xerostomia scores. In a subgroup of patients with a mean dose above 40 Gy, pilocarpine administration resulted in sparing of parotid gland function. Therefore, pilocarpine could be provided to patients in whom sufficient sparing of the parotid is not achievable. PMID- 17869019 TI - Multi-institutional review of repeat irradiation of chest wall and breast for recurrent breast cancer. AB - PURPOSE: To review the toxicity and clinical outcomes for patients who underwent repeat chest wall or breast irradiation (RT) after local recurrence. METHODS AND MATERIALS: Between 1993 and 2005, 81 patients underwent repeat RT of the breast or chest wall for locally recurrent breast cancer at eight institutions. The median dose of the first course of RT was 60 Gy and was 48 Gy for the second course. The median total radiation dose was 106 Gy (range, 74.4-137.5 Gy). At the second RT course, 20% received twice-daily RT, 54% were treated with concurrent hyperthermia, and 54% received concurrent chemotherapy. RESULTS: The median follow-up from the second RT course was 12 months (range, 1-144 months). Four patients developed late Grade 3 or 4 toxicity. However, 25 patients had follow-up >20 months, and no late Grade 3 or 4 toxicities were noted. No treatment-related deaths occurred. The development of Grade 3 or 4 late toxicity was not associated with any repeat RT variables. The overall complete response rate was 57%. No repeat RT parameters were associated with an improved complete response rate, although a trend was noted for an improved complete response with the addition of hyperthermia that was close to reaching statistical significance (67% vs. 39%, p = 0.08). The 1-year local disease-free survival rate for patients with gross disease was 53% compared with 100% for those without gross disease (p < 0.0001). CONCLUSIONS: The results of our study have shown that repeat RT of the chest wall for patients with locally recurrent breast cancer is feasible, because it is associated with acceptable acute and late morbidity and encouraging local response rates. PMID- 17869021 TI - A cone beam CT-Based Study for Clinical Target Definition Using Pelvic Anatomy During Postprostatectomy Radiotherapy. AB - PURPOSE: There are no accepted guidelines for target volume definition for online image-guided radiation therapy (IGRT) after radical prostatectomy (RP). This study used cone beam CT (CBCT) imaging to generate information for use in post-RP IGRT. METHODS AND MATERIALS: The pelvic anatomy of 10 prostate cancer patients undergoing post-RP radiation therapy (RT) to 68.4 Gy was studied using CBCT images obtained immediately before treatment. Contoured bladder and rectal volumes on CBCT images were compared with planning CT (CT(ref)) volumes from seminal vesicle stump (SVS) to bladder-urethral junction. This region was chosen to approximate the prostatic fossa (PF) during a course of post-RP RT. Anterior and posterior planning target volume margins were calculated using ICRU report 71 guidelines, accounting for systematic and random error based on bladder and rectal motion, respectively. RESULTS: A total of 176 CBCT study sets obtained 2 to 5 times weekly were analyzed. The rectal and bladder borders were reliably identified in 166 of 176 (94%) of CBCT images. Relative to CT(ref), mean posterior bladder wall position was anterior by 0.1 to 1.5 mm, and mean anterior rectum wall position was posterior by 1.6 to 2.7 mm. Calculated anterior margin as derived from bladder motion ranged from 5.9 to 7.1 mm. Calculated posterior margin as derived from rectal motion ranged from 8.6 to 10.2 mm. CONCLUSIONS: Normal tissue anatomy was definable by CBCT imaging throughout the course of post RP RT, and the interfraction anteroposterior motion of the bladder and rectum was studied. This information should be considered in devising post-RP RT techniques using image guidance. PMID- 17869020 TI - Fluorine-18-labeled fluoromisonidazole positron emission and computed tomography guided intensity-modulated radiotherapy for head and neck cancer: a feasibility study. AB - PURPOSE: Hypoxia renders tumor cells radioresistant, limiting locoregional control from radiotherapy (RT). Intensity-modulated RT (IMRT) allows for targeting of the gross tumor volume (GTV) and can potentially deliver a greater dose to hypoxic subvolumes (GTV(h)) while sparing normal tissues. A Monte Carlo model has shown that boosting the GTV(h) increases the tumor control probability. This study examined the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography ((18)F-FMISO PET/CT)-guided IMRT with the goal of maximally escalating the dose to radioresistant hypoxic zones in a cohort of head and neck cancer (HNC) patients. METHODS AND MATERIALS: (18)F FMISO was administered intravenously for PET imaging. The CT simulation, fluorodeoxyglucose PET/CT, and (18)F-FMISO PET/CT scans were co-registered using the same immobilization methods. The tumor boundaries were defined by clinical examination and available imaging studies, including fluorodeoxyglucose PET/CT. Regions of elevated (18)F-FMISO uptake within the fluorodeoxyglucose PET/CT GTV were targeted for an IMRT boost. Additional targets and/or normal structures were contoured or transferred to treatment planning to generate (18)F-FMISO PET/CT guided IMRT plans. RESULTS: The heterogeneous distribution of (18)F-FMISO within the GTV demonstrated variable levels of hypoxia within the tumor. Plans directed at performing (18)F-FMISO PET/CT-guided IMRT for 10 HNC patients achieved 84 Gy to the GTV(h) and 70 Gy to the GTV, without exceeding the normal tissue tolerance. We also attempted to deliver 105 Gy to the GTV(h) for 2 patients and were successful in 1, with normal tissue sparing. CONCLUSION: It was feasible to dose escalate the GTV(h) to 84 Gy in all 10 patients and in 1 patient to 105 Gy without exceeding the normal tissue tolerance. This information has provided important data for subsequent hypoxia-guided IMRT trials with the goal of further improving locoregional control in HNC patients. PMID- 17869022 TI - Efficacy and safety of subcutaneous amifostine in minimizing radiation-induced toxicities in patients receiving combined-modality treatment for squamous cell carcinoma of the head and neck. AB - PURPOSE: To report long-term data from a prospective trial of subcutaneous (s.c.) amifostine in patients who received chemoradiotherapy for squamous cell carcinoma of the head and neck (SCCHN). METHODS AND MATERIALS: Patients >or=18 years of age with previously untreated Stage III/IV SCCHN received fractionated radiotherapy, 1.8-2.0 Gy/day, 5 days per week, to a total dose of 70-72 Gy, plus weekly paclitaxel (40 mg/m2) and carboplatin (100 mg/m2) administered intravenously (i.v.) for 6 weeks. All patients received 500 mg s.c. amifostine 30-60 min before radiotherapy with antihistamine and antiemetic prophylaxis. RESULTS: Twenty patients were evaluable (median age, 55 years). The incidence of Grade 2 xerostomia was 42% and 29% at 12 and 18 months, respectively; there were no reports of Grade >or=3 xerostomia. Grade >or=3 mucositis occurred in 30% of patients, with median time to resolution of 12.5 weeks (range, 5-17 weeks). Survival estimates at 1 and 2 years were 95% and 71%, respectively. All patients experienced Grade 2 weight loss; 7 patients (35%) experienced Grade /=3 amifostine-related adverse events. CONCLUSIONS: Subcutaneous amifostine was well tolerated by patients receiving chemoradiotherapy for SCCHN, with lower rates of nausea/vomiting than reported in trials with i.v. amifostine. Xerostomia and mucositis rates were similar to those reported in trials with i.v. amifostine. PMID- 17869023 TI - Role of fractionated external beam radiotherapy in hemangioblastoma of the central nervous system. AB - PURPOSE: To assess the clinical outcomes and toxicity in patients receiving fractionated external beam radiotherapy (EBRT) for hemangioblastoma of the central nervous system, treated at two Canadian radiation oncology institutions. METHODS AND MATERIALS: Between January 1980 and December 2004, the data of all patients receiving EBRT for central nervous system hemangioblastoma were retrospectively reviewed. The patient, tumor, and treatment characteristics were collected and overall survival, disease-free survival, and EBRT-related toxicities assessed. RESULTS: A total of 18 cases, 5 associated with von Hippel Lindau disease (VHL) and 13 sporadic (non-VHL), with a total 31 lesions, were documented. These were located in the cerebellum in 20 and spinal cord in 8 patients. EBRT was delivered for recurrence in 12, adjuvantly for residual disease in 4, and definitively in 2. The EBRT schedules ranged from 50.0 to 55.8 Gy in 1.8-2.0-Gy daily fractions (n = 17), typically with parallel-opposed fields to the cerebellar target volumes and direct posterior fields for spinal disease. At a median follow-up of 5.1 years (range, 0.1-14.5), the 5-year OS rate was 69% (95% confidence interval [CI], 50-96%), decreasing to 30% (95% CI, 10-87%) at 10 years. The disease-free survival rate at 5 and 10 years was 57% (95% CI, 37-87%) and 30% (95% CI, 11-83%), respectively. The outcomes differed according to VHL status. The 5-year OS rate was 100% for those with VHL compared with 55% (95% CI, 32-95%) for those with non-VHL disease (log-rank p = 0.003), and the 5-year disease-free survival rate was 80% (95% CI, 52-100%) with VHL compared with 48% (95% CI, 26-89%) without (log-rank p = 0.036). CONCLUSIONS: Fractionated EBRT has a role in the management of extensive intracranial and/or spinal cord disease, the adjuvant treatment of residual postoperative disease, and the treatment of recurrence. More favorable outcomes were reported for VHL-associated lesions than for sporadic cases. PMID- 17869024 TI - Long-term outcome after static intensity-modulated total body radiotherapy using compensators stratified by pediatric and adult cohorts. AB - PURPOSE: To report the long-term outcome after total body irradiation with intensity-modulating compensators and allogeneic/autologous transplantation, especially in terms of therapy-related toxicity in pediatric and adult cohorts. METHODS AND MATERIALS: A total of 257 consecutive patients (40 children and 217 adults) have been treated since 1983 with TBI using static intensity-modulated radiotherapy for hematologic malignancies. The total dose of 12 Gy was applied in six fractions within 3 days before allogeneic (n = 174) or autologous (n = 83) transplantation. The median follow-up was 9.2 years. RESULTS: The 5-year overall survival rate was 47.9% (49.8% for the adults and 37.5% for the children, p = 0.171). The 5-year tumor-related mortality rate was 23%, and the 5-year treatment related mortality rate 29.2% (29.5% in the adults and 27.5% in the pediatric patients). Interstitial pneumonitis developed in 28 (10.9%) of 257 patients and in 12.5% of the pediatric cohort. The interstitial pneumonitis rate was 25% in pediatric patients treated with a 12-Gy lung dose compared with 4.2% for those treated to an 11-Gy lung dose. The overall survival rate stratified by lung dose was 26.7% for 12 Gy and 52.4% for 11 Gy (p = 0.001). The incidence of veno occlusive disease and cataract was 5.8% and 6.6% in all patients and 12.5% and 15% in the pediatric patients, respectively (p < 0.05). Secondary malignancies were found in 4.3% of all patients, all in the adult cohort at transplantation. CONCLUSION: Static intensity-modulated total body irradiation with a total dose of 12 Gy before allogeneic/autologous transplantation is a successful treatment with good long-term outcome and acceptable therapy-related toxicities. Constraining the lung dose to 11 Gy substantially lowered the actuarial treatment related mortality. This effect was especially striking in the pediatric patients. PMID- 17869025 TI - Quantification of motion of different thoracic locations using four-dimensional computed tomography: implications for radiotherapy planning. AB - PURPOSE: To assess the respiratory motion of different thoracic nodal locations and its dependence on the presence of enlarged nodes; to assess the respiratory motion of different parenchymal tumor locations; and to determine the appropriate margins to cover the respiratory motion of targets at these locations. METHODS AND MATERIALS: We reviewed the four-dimensional computed tomography scans of 20 patients with thoracic tumors treated at our institution. The motion of four central thoracic locations (aortic arch, carina, and bilateral hila), parenchymal tumor locations (upper vs. lower, and anterior vs. middle vs. posterior thorax), and bilateral diaphragmatic domes was measured. RESULTS: For the central thoracic locations, the largest motion was in the superoinferior (SI) dimension (>5 mm for bilateral hila and carina, but <4 mm for aortic arch). No significant difference was found in the motion of these locations in the absence or presence of enlarged nodes. For parenchymal tumors, upper tumors exhibited smaller SI motion than did lower tumors (3.7 vs. 10.4 mm, p = 0.029). Similarly, anterior tumors exhibited smaller motion than did posterior tumors in both the SI (4.0 vs. 8.0 mm, p = 0.013) and lateral (2.8 vs. 4.6 mm, p = 0.045) directions. The margins that would be needed to encompass the respiratory motion of each of the evaluated locations in 95% of patients were tabulated and range from 3.4 to 37.2 mm, depending on the location and direction. CONCLUSIONS: The results of our study have provided data for appropriate site-specific internal target volume expansion that could be useful in the absence of four-dimensional computed tomography-based treatment planning. However, generalizing the results from a small patient population requires discretion. PMID- 17869026 TI - [Evaluation of the instruction and the instructors by the students during a clinical training period in a gynecology and obstetrics unit]. AB - OBJECTIVES: The evaluation of an educational system is part of the essential process to get high-quality teaching. We wanted to assess the teaching and the teachers in a gynaecological unit with a view to improve the education of the trainees within a dynamic educational system. MATERIALS AND METHODS: It is a prospective study which took place in the gynecology-obstetric unit of the University of Nantes. Thanks to a questionnaire called "Evaluation of the teaching during a gynecologic-obstetric training course", we evaluated the feelings of 21 medical students about their two-month training course. This questionnaire of 27 items is divided in several parts. The first one is about the quality of the teaching, the second about planification, the third about the quality of the learning resources, and the fourth is about the educational quality of each teacher (interaction teacher-student). The fifth one evaluates the perception of this work experience by the student, notably his clinical activity and his personal implication in the unity. There are also some open questions which point out the positive aspects of the teaching but also its failings and the parts that must be improved. We give here the details of the different stages of this assessment from the questionnaire up to the results, mentioning their limits considering the conceptual orientations and the methodological orientations chosen. RESULTS: Analysis of the data was done determining the percentage of agreement and disagreement to a statement of the questionnaire. All the students find the teachings interesting and stimulating, objectives were gone through thoroughly. Courses were well organised. Their integration in the medical team was good. They feel responsible especially when they are on call (88.3%). On the other hand, for a quarter of them, educational supports are not adapted, teaching documents are not clear and adapted to the National Test. Half of them (45%) are not satisfied by the numerical campus which does not facilitate understanding. Staffs are not an opportunity to learn for 37% of them. Management by senior doctors is insufficient. CONCLUSION: Students are completely integrated into the process of evaluation but concrete actions to improve the teaching have to be realised in the hospital departments. Questionnaire is an informative and adapted tool. It permits to highlight the flaws in the learning process and to remedy them. PMID- 17869027 TI - Smaller feedback ERN amplitudes during the BART are associated with a greater family history density of alcohol problems in treatment-naive alcoholics. AB - BACKGROUND: Alcoholism is characterized by impaired decision-making (i.e., choosing intoxication in the face of mounting negative consequences). This impairment may involve a reduced brain response to the negative consequences of behavior, which supports an inclination to engage in risky behaviors. The feedback error-related negativity (F-ERN) is hypothesized to reflect the valence attached to the negative consequences of behavior. Performance on the Balloon Analogue Risk Task (BART) measures risk-taking propensity. We recorded F-ERNs during the BART and during a BART simulation, where individuals observed the rewards and consequences of (someone else's) BART performance. METHODS: EEGs were recorded on 22 actively drinking, treatment-naive alcoholics during the BART and BART simulation. F-ERNs were measured and their association with psychological and alcohol use measures was examined. RESULTS: F-ERNs over fronto-central electrode sites were observed to balloon pops in the BART and BART simulation. F ERNs during the BART were more than twice the amplitude of F-ERNs during the BART simulation. Smaller F-ERN amplitudes from the BART (but not the BART simulation) were associated with a greater family history density of alcohol problems. CONCLUSION: The results suggest a possible link between the genetic vulnerability toward developing alcoholism and the brain's response to the negative consequences of behavior. PMID- 17869028 TI - An analysis of racial and sex differences for smoking among adolescents in a juvenile correctional center. AB - The purpose of this study was to investigate racial and sex differences on the risk factors for smoking initiation and daily smoking among juvenile justice adolescents, a population that is traditionally ignored in school-based epidemiological samples. This study used archival data collected by juvenile justice authorities for a large sample of juvenile justice adolescents (N=4381), examining interaction terms to determine race and sex differences for risk factors. About 70% of juvenile justice adolescents reported ever having smoked cigarettes while almost half reported daily smoking. Overall predictors of ever and daily smoking included older age, being female, White, use of alcohol, cannabis, and cocaine in the past year, affiliation with smoking peers, not living with at least one parent, and a diagnosis of ADHD. While differences were seen between individual predictor models for both race and sex, the interaction terms did not add significantly to the overall model. These important racial and gender differences in this study suggest that tailored prevention messages and interventions may be needed to be most effective with adolescents in the juvenile justice system. While this study provides a basic foundation of risk factors for smoking among juvenile justice adolescents, future research is needed to assess the efficacy of treatment and prevention interventions with this high risk group of adolescent smokers. PMID- 17869029 TI - The impact of early school behavior and educational achievement on adult drug use disorders: a prospective study. AB - Few longitudinal studies have examined the effects of education on drug use disorders among community populations of African Americans. This study explores the impact of multiple early education indicators on later problem drug use in an African American population followed for more than 35 years. The initial cohort comprised all 1st graders (N=1242, 51% female) living in the Woodlawn community of Chicago in 1966. Follow-up assessments were conducted in adolescence (1975 76), early adulthood (1992-93), and mid adulthood (2002-03). One or both adult interviews were completed by 1053 individuals providing information for identifying lifetime drug use disorders. Logistic regression with multiple imputation revealed several important relationships between early education indicators and DSM-III-R/DSM-IV drug use disorders. Specifically, the risk for adult problem drug use was related to: underachievement in 1st grade; low 7th and 8th grade standardized math scores; both suspension from and skipping school in adolescence; not having a high school diploma (compared to having a college degree), and having a diploma or GED (compared to having a college degree). Also, 1st graders characterized as shy by their teachers were less likely to develop problem drug use in adulthood. Results indicate potential opportunities for targeted intervention at multiple life stages. PMID- 17869030 TI - The influence of legal coercion on dropout from substance abuse treatment: results from a national survey. AB - Legal coercion is frequently used to leverage substance abuse treatment upon persons who would otherwise not seek it voluntarily. Various methodological and conceptual problems of the existing research have prevented a clear understanding of its effectiveness. The influence of legal coercion on retention in substance abuse treatment was examined using a national survey of programs in the public sector of care and three different treatment modalities including short-term residential (N=756), long-term residential (N=757), and outpatient treatment (N=1181). Legal coercion was found to reduce the risk of dropout across all three treatment modalities. The greatest effect was among persons in short-term residential treatment. The smallest effect was observed in outpatient treatment. This study shows that legal coercion significantly reduces the risk of dropout in substance abuse treatment. However, the differential effects across treatment conditions must be carefully considered when using coercion to involve individuals in treatment. PMID- 17869031 TI - Experimental trial in heifers vaccinated with Staphylococcus aureus avirulent mutant against bovine mastitis. AB - Staphylococcus aureus, is the most frequently isolated pathogen from cases of bovine mastitis. Vaccination against S. aureus seems to be a rational approach for the control of staphylococcal mastitis. In the present work we evaluate the response of heifers vaccinated with a S. aureus avirulent mutant to the intramammary challenge with a S. aureus virulent strain. Clinical signs, production of milk, shedding of S. aureus cells, somatic cell count (SCC) and antigen-specific IgG in blood and milk, were determined. Two subcutaneous doses of a culture of the mutant, used as vaccine, was administered to four pregnant heifers 30 and 10 days before calving. The vaccinated heifers and four non vaccinated were challenged 10 days after calving with the homologous virulent S. aureus strain, which was inoculated by intramammary route into two quarters of each animal. No local tissue damage was observed due to the administration of the vaccine. A significantly increase of specific IgG to S. aureus RC122 was detected in blood and milk of vaccinate heifers as well as a slight increase in daily milk yield during the trial. No significant difference on shedding of bacteria in milk and SCC were found among groups. In conclusion, vaccination of heifers before calving by an avirulent mutant vaccine of S. aureus, induced specific and significant antibody responses and provide better post-challenge conditions in vaccinated heifers. PMID- 17869033 TI - Sexual maturity and reproductive phase of oocyte donor influence the developmental ability and apoptosis of cloned and parthenogenetic porcine embryos. AB - This study investigated the influence of the sexual maturity and reproductive phase of oocyte donor on the developmental ability and quality of porcine embryos produced by somatic cell nuclear transfer (SCNT) or parthenogenesis (PA). Blastocyst quality was evaluated in terms of hatching ability, total nuclei number and types of apoptosis. Results revealed that maturation rate was not influenced by the reproductive status of the oocyte donor. However, when subjected to PA or SCNT, embryos derived from sexually mature sow oocytes developed to blastocysts at higher rates and had higher cell number than those derived from immature gilt oocytes (p<0.05). Significant effect of reproductive phase, luteal versus follicular, was also noted with luteal stage oocytes yielding higher (p<0.05) rate of blastocyst formation (PA: 54.3+/-1.3% versus 44.8+/-0.3%; SCNT: 29.4+/-0.2% versus 22.7+/-0.1%). Blastocysts derived from luteal phase oocytes also had higher (p<0.05) hatching ability (PA: 44.2+/-1.1%; SCNT: 39.6+/-4.7%) and cell number (PA: 77.4+/-4.9; SCNT: 54.9+/-2.4) than those derived from follicular phase oocytes (PA: 34.9+/-0.9%, 67.2+/-3.9; SCNT: 34.6+/ 2.7%, 47.5+/-2.9). TUNEL assay and Hoechst 33342 staining revealed that percentage of blastocysts showing total apoptosis did not differ among the groups. However, luteal phase oocyte-derived blastocysts had the highest incidence of nuclear fragmentation. Among cloned blastocysts that showed the signs of apoptosis, the highest index of total apoptosis was observed in prepubertal oocyte-derived blastocysts (5.2+/-0.7). Blastocysts derived from luteal phase oocytes showed the lowest TUNEL index (2.0+/-0.5). The present study therefore, indicates that the sexual maturity and reproductive phase of cytoplast donor significantly influences the developmental ability, apoptosis and quality of blastocysts produced by SCNT or PA. Oocytes from sexually mature sows in luteal phase of their reproductive cycle may be better cytoplast recipients for SCNT. PMID- 17869032 TI - Genetic diversity of porcine reproductive and respiratory syndrome virus strains circulating in Hungarian swine herds. AB - Analysis of 37 ORF5 sequences of Hungarian porcine reproductive and respiratory syndrome virus (PRRSV) strains revealed that most of them (35) belonged to the European genotype, forming distinct subgroups, reflecting the exceptional diversity of Eastern European strains. Twelve vaccine-like strains were also found in non-vaccinated animals. Two strains belonged to the American genotype showing 90-91% nucleotide identity to the "Quebec" Canadian reference strain. The analysis of the putative ectodomains and their N-linked glycosylation sites of the vaccine strain and its variants suggested selective pressure on the first ectodomain, by a consistent amino acid change on epitope B and by loosing a glycosylation site in the otherwise conserved N-46 position. PMID- 17869034 TI - Influence of various combinations of mucolytic agent and non-ionic surfactant on intestinal absorption of poorly absorbed hydrophilic compounds. AB - The absorption enhancing effects of various combinations of a mucolytic agent and a non-ionic surfactant on the intestinal absorption of poorly absorbed hydrophilic compounds were examined. Fluorescein isothiocyanate-labeled dextran with an average molecular weight of ca. 4.4 kDa (FD-4) was used as a model compound. Cysteine derivatives such as N-acetylcysteine (NAC), S carboxymethylcysteine (SCMC), S-ethylcysteine (SEC), and S-methylcysteine (SMC) were selected as mucolytic agents. A homogeneous series of single chain polyoxyethylene alkyl ethers were employed as non-ionic surfactants. Various dosing solutions were administered into rat jejunum, and the bioavailability of FD-4 was determined. Unlike NAC, the agents such as SCMC, SEC, and SMC, which do not possess a free thiol group, did not show any apparent enhancement of intestinal FD-4 absorption, when they were co-administered with p-t-octyl phenol polyoxyethylene-9.5 (Triton X-100, TX-100). In addition, the absorption enhancement was dependent on the kinds of polyoxyethylene alkyl ethers used, when used in combination with NAC. For a constant alkyl chain of 12 with a varying polyoxyethylene (POE) chain length, the surfactant with a short to medium POE chain length such as lauryl poly (4.2) oxyethylene ether (BL-4.2) and lauryl poly (9) oxyethylene ether (BL-9) were effective. In addition, for a constant alkyl chain of 18 with a varying POE chain length, the surfactants with a longer POE chain length such as oleyl poly (15) oxyethylene ether (BO-15) and stearyl poly (20) oxyethylene ether (BS-20) showed the effective enhancement. All these results suggest that a mucolytic agent not possessing a free thiol group is not effective for enhancing the intestinal absorption of poorly absorbed hydrophilic compounds. Also, they indicate that the combination of a mucolytic agent possessing a free thiol group and a non-ionic surfactant either with a short to medium POE chain length and a medium alkyl chain length, or with a longer POE chain length and a longer alkyl chain length shows the effective enhancement. This fundamental information might be useful for finding the optimal combination. PMID- 17869035 TI - Stabilization and encapsulation of photosensitive resveratrol within yeast cell. AB - The photosensitive resveratrol was successfully encapsulated in yeast cells for the first time, as characterized by FT-IR spectra, fluorescence and confocal micrographs of the yeast cells, resveratrol and microcapsules. The release characteristic of the obtained yeast-encapsulated resveratrol in simulated gastric fluid was evaluated, and its storage stability as a powder was investigated at 25 degrees C/75% relative humidity (RH), 25 degrees C/90% RH and 60 degrees C under the laboratory fluorescent lighting conditions (ca. 300 lx) or in the dark. Also, the scavenging capacity of yeast-encapsulated resveratrol on DPPH radical was compared with that of non-encapsulated resveratrol. It could be demonstrated clearly that no chemical changes occurred during the encapsulation. Besides, the DPPH radical-scavenging activity increased after the encapsulation. In addition, the yeast-encapsulated resveratrol exhibited good stability, and its bioavailability was enhanced as a result of increased solubility of resveratrol and sustained releasing. PMID- 17869036 TI - Block copolymers for drug solubilisation: relative hydrophobicities of polyether and polyester micelle-core-forming blocks. AB - Published values of the critical micelle concentration are tabulated for diblock copolymers E(m)P(n), E(m)B(n), E(m)S(n), E(m)L(n), E(m)VL(n) and E(m)CL(n), where E denotes a chain unit derived from ethylene oxide, P from propylene oxide, B from 1,2-butylene oxide, S from styrene oxide, L from dl-lactide, VL from gamma valerolactone and CL from epsilon-caprolactone, and the subscripts denote average chain lengths. Noting that log(cmc/moldm(-3) is proportional to the standard Gibbs energy of micellisation, the dependence of this quantity on hydrophobic block length (n) is explored for a given E-block length. Superposition of data allows ranking of the hydrophobicities of the chain units. The ratios relative to the least hydrophobic unit are: P : L : B : VL : S : CL = 1 : 4 : 6 : 10 : 12 : 12 Transitions in the slope of log(cmc) versus n are assigned to changes in the unimer-micelle equilibrium and related to the formation of unimolecular micelles and, at high values of n, to the completion of that process. The formation transition is seen in the plots for all the copolymers except the least hydrophobic, E(m)P(n). The completion transition is seen in the plots for E(m)CL(n) and E(m)L(n) copolymers, as these alone include results for copolymers with very lengthy hydrophobic blocks. PMID- 17869037 TI - Neutron activation based gamma scintigraphic evaluation of enteric-coated capsules for local treatment in colon. AB - The fate of two colon-specific formulations developed in our previous study was investigated using a gamma scintigraphic imaging method. The formulations contained paracetamol and samarium oxide (Sm2O3) and either microcrystalline cellulose (MCC) or hypromellose (HPMC K4M) as diluent and were coated with Eudragit S polymer. The gamma scintigraphic evaluation proved that the products remained intact in the stomach and the upper gastrointestinal tract. The gastric residence time was less that 1h. Three to four hours after administration the formulations had reached the ileo-caecal junction, i.e. the small intestine transit time was approximately 3h. The capsules disintegrated in the ileo-caecal junction or in the ascending colon. The capsules containing MCC released the marker momentarily, the capsules containing HPMC K4M gradually spreading it to the whole colon. The gamma images also verified that the HPMC gel disintegrates completely in 12-14 h. While comparing the results to those previously obtained from the bioavailability studies it could be concluded that it is possible to develop colon specific drug products that begin releasing the drug in the ileo caecal junction or at the beginning of the ascending colon and spread the drug dose to a larger surface area by using enteric coats and hydrophilic polymers. PMID- 17869038 TI - Screening for the anti-inflammatory activity of fractions and compounds from Atractylodes macrocephala koidz. AB - The aim of this study was to screen for the anti-inflammatory activity of fractions and compounds from Atractylodes macrocephala Koidz. The rhizomes of Atractylodes macrocephala were treated with supercritical CO(2) fluid and the extract was separated by normal-phase and reverse-phase column chromatography. The separated samples were screened with white blood cell membrane (WBCM) chromatography (WBCM-C). The anti-inflammatory effects of these fractions and components were tested pharmacologically in vivo. The results indicated that the retention characteristics of the petrol-ether (1:1, v/v) fraction (BZC-2) of the supercritical CO(2) extract, the atractylenolide I and 14-acetoxy-12 senecioyloxytetradeca-2E,8E,10E-trien-4, 6-diyn-1-ol isolated from BZC-2 as active fractions and components were similar to that of dexamethasone in WBCM-C. Therefore, they may act on WBCM and its receptors. BZC-2 has shown anti inflammatory effects in acute and chronic inflammation models in rats and mice. Oral administration of atractylenolide I and 14-acetoxy-12-senecioyloxytetradeca 2E,8E,10E-trien-4,6-diyn-1-ol produced significant anti-inflammatory effects in acute and chronic inflammation models in mice. The screening results with WBCM-C were correlated significantly with pharmacological effects in vivo. Atractylenolide I and 14-acetoxy-12-senecioyloxytetradeca-2E,8E,10E-trien-4,6 diyn-1-ol were the main components of Atractylodes macrocephala that were effective as anti-inflammatory agents. PMID- 17869039 TI - Antihyperglycemic activity of kinsenoside, a high yielding constituent from Anoectochilus roxburghii in streptozotocin diabetic rats. AB - Different doses of kinsenoside, a high yielding constituent from Anoectochilus roxburghii, was orally administered to further investigate its biological activity and pharmacological mechanisms that involve in the hypoglycemic effect on streptozotocin (STZ) diabetic rats. Our study showed that this compound exhibited significantly antihyperglycemic activity at the dose of 15mg/kg body weight, which is speculated to be partially attributed to modulating the activity of enzymatic antioxidants, scavenging free radicals, and reducing the content of factor NO. Much more intact beta cells in the islets of Langerhans with denser insulin in kinsenoside-treated groups than the negative control were observed, which greatly supported the morphological and functional elucidation. These results displayed that kinsenoside could be useful for repairing beta cells in pancreatic islet injury as well as improving its function. The OGTT evidenced that this compound could promote the glucose tolerance of acute glucose increase in both diabetic and normal healthy rats. PMID- 17869040 TI - Reconstruction of ripped-up documents using fragment stack analysis procedures. AB - Reconstruction of ripped-up documents can be a very time-consuming task for forensic experts. Currently, this task is often carried out using various homespun or loosely defined procedures. Under the main assumption that a (partially) ordered set of fragments can be recovered, we propose and discuss a more formal analysis methodology for this type of reconstruction problem. We discuss several complications that can occur in real-life problems and illustrate the efficiency of the proposed methods. Although several avenues for further research remain, we show that the proposed approach offers both a better understanding of the problem, as well as important strategies for devising very fast manual and semi-automatic fragment reassembly procedures. PMID- 17869041 TI - Intralabyrinthine schwannomas: symptoms and managements. AB - OBJECTIVE: To describe the characteristic presentations, radiologic findings and managements of the intralabyrinthine schwannomas. METHOD: Retrospective review of patient records, their managements, and review of the literature. RESULT: Four patients with a variety of otologic symptoms including hearing loss, vertigo, and tinnitus were found to have a schwannomas involving the labyrinth. In all cases, the inner ear lesions were preoperatively identified on magnetic resonance imaging, and the surgical removals were performed in all patients without serviceable hearing. The patients experienced improvement in their vertigo and tinnitus after surgery. Two patients were implanted the Bone-Anchored Hearing Aid (BAHA) to reconstruct the pseudo-stereophonic hearing. CONCLUSION: Intralabyrinthine schwannomas are the rare tumours in the otology. The tumour can be removed by surgical approach, but we do not propose surgical excision for the patients with serviceable hearing. BAHA can give patients a post-operative monaural pseudo-stereophonic hearing. PMID- 17869042 TI - Supracricoid laryngectomy with cricohyoidoepiglotto-pexy or cricohyoido-pexy: experience on 32 patients. AB - OBJECTIVE: Supracricoid laryngectomy (SCL) with Cricohyoidoepiglotto-pexy (CHEP) or Cricohyoido-pexy (CHP) is an organ preservation surgery indicated for early and selected advanced laryngeal cancers. To verify the clinical usefulness of supracricoid laryngectomy versus total laryngectomy, a retrospective review was conducted. METHODS: We summarized the clinical and postoperative data of 32 patients who received SCL over the past 9 years (1997-2005). Five-year survival rate of the SCL patient group (29 cases) was compared with that of the patient group receiving total laryngectomy (35 cases) within the same period. RESULTS: Wound infection was detected in 12 patients (38%). Those with severe infection, which required surgical intervention, included two cases of ruptured pexis and two cases showing cricoid cartilage necrosis induced by Forestier disease. There were two T4 cases that resulted in extensive excision. In one case, excision involved the posterior part of the cricoid cartilage resulting in insufficient closure of the neoglottis; the patient received total laryngectomy 30 months after SCL-CHEP because of persistent aspiration of liquid diet. In the other T4 case, the tumor invaded the thyroid and arytenoid cartilages but not the cricoid cartilage. Reposition of the remaining corniculate cartilage resulted in sufficient closure of the neoglottis; this patient subsequently acquired satisfactory laryngeal function. The 5-year overall survival rate was 86% for SCL group and 61% for the total laryngectomy group (limited to Stages III and IV glottic cancers). The causes of the four deaths were distant metastasis, neck metastasis, and intercurrent disease, respectively. Two patients are alive with distant disease. CONCLUSION: Through our experience in this series, the functional and oncological results of SCL showed certain advantages over those of total laryngectomy. Particularly, the clinical impact of SCL-CHEP was impressive; this technique needs is recommended to both head and neck surgeons and patients. PMID- 17869043 TI - Arsenic trioxide induced the apoptosis of laryngeal cancer via down-regulation of survivin mRNA. AB - OBJECTIVE: Arsenic trioxide (As(2)O(3)) is used clinically to treat acute promyelocytic leukemia and has activity in vitro against several solid tumor cell lines, where induction of differentiation and apoptosis are the prime effects. As a novel anticancer agent for treatment of solid cancers, As(2)O(3) is promising and the mechanism has been not still fully understood. Laryngeal squamous cell carcinoma (LSCC) is one common tumor in head and neck cancers. The objective of this study was to investigate the effects of As(2)O(3) on LSCC cell line HEP-2, and their possible involvement in As(2)O(3)-induced apoptosis. METHODS: The cell viability was analyzed by MTT assay method and the morphological changes were observed by an inverted microscope and acridine orange (AO) staining. The caspase 3 activity was measured by a fluorophotometer. The expression of survivin mRNA was evaluated by RT-PCR. RESULTS: In this study, we demonstrated an apoptotic effect of As(2)O(3) in LSCC cell line Hep-2. In Hep-2 cells, As(2)O(3) decreased the cell viability, inhibited the growth and proliferation, induced apoptosis and increased the activity of caspase-3 in a dose-dependent manner. And the expression of survivin mRNA was also decreased in a dose-dependent manner. CONCLUSION: We concluded that As(2)O(3) induced the apoptosis of Hep-2 cells via down-regulating the expression of survivin mRNA. PMID- 17869044 TI - Distortion-product otoacoustic emission: early detection in deferoxamine induced ototoxicity. AB - OBJECTIVE: Deferoxamine therapy in lifelong transfusion-dependent anaemias, as beta-thalassemia major, is associated with an increased risk of ototoxic changes. With increasing survival rates, prevention and/or early detection of ototoxicity are important for providing management options. The predictive value of pure-tone audiometry in early detection of ototoxicity has been questioned, particularly in the higher frequencies. Otoacoustic emissions appear to be more sensitive to cochlear insult than the conventional pure-tone audiometry. The aim of our study was to compare the efficacy of otoacoustic emissions (distortion-product otoacoustic emissions) with that of pure-tone audiometry as method of audiological monitoring. METHODS: Baseline audiometric (0.25-8kHz) and otoacoustic emission testing (distortion-product otoacoustic emissions) was conducted in a group of patients with beta-thalassemia major, 60 of whom met the criteria for inclusion in the study. Comparisons were performed between baseline measurements and those recorded after 20 months. Distortion-product otoacoustic emissions were obtained as DP-grams. The DP-gram amplitude was determined for each child. RESULTS: Threshold changes from baseline were found to be statistically significant from 4 to 8kHz in 68.4% of the subjects (P<0.01). Distortion-product otoacoustic emissions demonstrated a significant threshold shift and a decreased amplitude in the frequencies >3kHz (P<0.05). Furthermore, DP-gram amplitude also reduced significantly at 3kHz (P<0.05) without any similar change in pure-tone audiometry. CONCLUSIONS: As ototoxicity screening tool DP gram was extremely sensitive and superior to pure-tone audiometry. Their use is recommended for regular monitoring of cochlear function, aiming in prevention of permanent damage. PMID- 17869045 TI - Influence of visual information and test paradigm on clinical olfactory test results. AB - OBJECTIVE: The goal of this study was to determine if visual information and test paradigms affect clinical olfactory test results. METHODS: Three hundred and ninety-seven Japanese patients with complaints of olfactory dysfunction were administered both a new clinical olfactory test, the Odor Stick Identification Test for Japanese (OSIT-J), and the Japanese benchmark olfactory test, T&T olfactometry. Four different methods were used to administer the OSIT-J combining paradigms using word or picture-word alternatives with the four-plus alternative method based on a top-down strategy or the two-step identification method based on a bottom-up strategy. OSIT-J scores were compared for the different methods, referring to benchmark scores obtained with T&T olfactometry. RESULTS: OSIT-J scores using picture-word alternatives and the four-plus alternative method showed a stronger correlation with T&T olfactometry test scores than those using word alternatives and the two-step identification method, respectively. The average OSIT-J scores of the four-plus alternative method using picture-word alternatives were significantly higher than those using word alternatives in anosmic and severely hyposmic patients. The time required to administer the OSIT J using both picture-word alternatives and the four-plus alternative method was the shortest of the four OSIT-J methods. CONCLUSIONS: Visual information and test paradigms may affect clinical olfactory test results. The OSIT-J method using picture-word alternatives and the four-plus alternative method may be the most suitable for clinical practice. PMID- 17869046 TI - Hemostasis factors and aging. AB - With advancing age, an increasing number of healthy individuals have laboratory signs of heightened coagulation enzyme activity. Such biochemical hypercoagulability might be the basis of either the increased thrombotic tendency occurring with age or a harmless manifestation of this process. Centenarians had striking signs of heightened coagulation enzyme activity, accompanied by signs of enhanced formation of fibrin and secondary hyperfibrinolysis. Plasma concentrations of fibrinogen and factor VIII were higher than in controls, whereas other coagulation factors were not elevated. It is of interest that centenarians have a significantly higher frequency than young individuals of the high risk 4G allele of the PAI-1-675 (4G/5G) polymorphism, mutant factor V (Arg506Gln) and prothrombin gene G20210A mutation. Von Willebrand factor (VWF), a well-known independent predictor of atherothrombotic disease, was increased in centenarians, independently of the blood group, confirming the previous results of a state of hypercoagulability. The finding that the VWF cleaving proteases levels are low when VWF levels are high in centenarians could be a corollary of the previous described paradox of successful aging, adding another marker of increased risk of atherothrombosis to the scenario. Alike, high prevalence of anti-phospholipids antibodies, not associated with an anti-phospholipid syndrome has been described in centenarians. In conclusion, the data show the oldest old do not escape the state of hypercoagulability associated with aging, but that this phenomenon is compatible with health and longevity. Hence, high plasma levels of the coagulation activation markers in older populations do not necessarily mirror a high risk of arterial or venous thrombosis. PMID- 17869047 TI - A continuous correlation between oxidative stress and telomere shortening in fibroblasts. AB - Telomere shortening in cells with low intrinsic telomerase activity like fibroblasts is governed by various mechanisms including the so-called end replication problem, end processing and oxidative DNA damage. To assess the impact of oxidative stress on telomere shortening rates, we compared telomere shortening rates measured in fibroblasts from two different donor species (human and sheep) under both pro- and antioxidative culture regimes. Over an almost 50 fold change in peroxide indicator dye fluorescence intensity, we found a continuous, exponential correlation between cellular oxidative stress levels and telomere shortening rates, which was independent of donor species and cell strain. This correlation suggests stress-mediated telomere DNA damage as an important determinant of telomere shortening. PMID- 17869048 TI - Complement Factor H polymorphism Y402H associates with inflammation, visual acuity, and cardiovascular mortality in the elderly population at large. AB - The haplotype tagging Y402H polymorphism in the Complement Factor H gene (CFH) has consistently been associated with age-related macular degeneration, whereas conflicting results have been reported on its relationship with cardiovascular disease. CFH plays a role in inflammation, which is causal to both diseases and both are highly prevalent in old age. Therefore, we investigated whether or not Y402H associated with inflammation, visual acuity, and cardiovascular disease in old age. Within the Leiden 85-plus Study, a prospective population-based study of participants aged 85 years and older, we found that carriers of the CFH 402HH variant had a higher production of IL-6 in whole blood samples compared to those carrying the 402YY variant (P=0.029). Carriers of the 402HH genotype also had a steeper increase in circulating C-reactive protein levels during follow-up (P=0.009), lower visual acuity (P=0.020), and an increased risk of cardiovascular mortality (P=0.004). Subjects in the lowest tertile of visual acuity had a twofold increased risk of cardiovascular mortality compared to those in the highest tertile (P=0.001). We conclude that the CFH Y402H polymorphism associates with inflammation, visual impairment, and cardiovascular mortality in the elderly population at large. Visual impairment identifies elderly with an increased risk of cardiovascular disease. PMID- 17869049 TI - Impact of methadone on drug use and risky sex in China. AB - This study examined the impact of methadone on drug-using and risky sexual behaviors among 557 heroin injection drug users in one of the first methadone programs in China. Structured questionnaires were administered to collect data on methadone utilization, drug use, and risky sexual behaviors. Blood samples were tested for blood-borne infections. Multivariate logistic analyses revealed that, among opioid-addicted individuals, methadone participants were less likely to use or inject drugs and share needles than nonparticipants. They also were less likely to have multiple sexual partners or have unprotected sex. Those currently enrolled in methadone maintenance had lower risk of using and injecting drugs than those who were no longer receiving methadone. Data suggest positive, short term impact on these important behaviors, but further studies are needed to examine the long-term impact of methadone treatment on disease rates. PMID- 17869050 TI - The interactive effects of antisocial personality disorder and court-mandated status on substance abuse treatment dropout. AB - The present study sought to examine the interactive effects of court-mandated (CM) treatment and antisocial personality disorder (ASPD) on treatment dropout among 236 inner-city male substance users receiving residential substance abuse treatment. Of the 236 participants, 39.4% (n = 93) met criteria for ASPD and 72.5% (n = 171) were mandated to treatment through a pretrial release-to treatment program. Results indicated a significant interaction between ASPD and CM status, such that patients with ASPD who were voluntarily receiving treatment were significantly more likely to drop out of treatment than each of the other groups. Subsequent discrete time survival analyses to predict days until dropout, using Cox proportional hazards regression, indicated similar findings, with patients with ASPD who were voluntarily receiving treatment completing fewer days of treatment than each of the other groups. These findings suggest the effectiveness of the court system in retaining patients with ASPD, as well as the role of ASPD in predicting treatment dropout for individuals who are in treatment voluntarily. Implications, including the potential value of the early implementation of specialized interventions aimed at improving adherence for patients with ASPD who are receiving treatment voluntarily, are discussed. PMID- 17869051 TI - The adolescent cannabis check-up: randomized trial of a brief intervention for young cannabis users. AB - The aim of this study was to evaluate the efficacy of a brief motivational enhancement therapy in reducing cannabis use and cannabis-related problems in a population of non-treatment-seeking adolescent cannabis users. In a randomized controlled trial, 40 young people (aged 14-19 years) were randomly assigned to either a two-session brief intervention or a 3-month delayed-treatment control condition. The intervention consisted of a detailed assessment and a session of motivational enhancement therapy. An additional optional discussion of skills for reducing or quitting cannabis use was offered if a participant was interested in discussing these issues. Primary outcome measures were changes in days of cannabis use, mean quantity of cannabis used weekly, and number of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition dependence symptoms reported. Significantly greater reductions on these measures were found in the Adolescent Cannabis Check-up group at 3-month follow-up. Between-group effect sizes were moderate. The approach is acceptable to participants and merits further evaluation with this difficult to reach population. PMID- 17869052 TI - Interpersonal violence exposure and alcohol treatment utilization among medical inpatients with alcohol dependence. AB - The goal of this study was to examine the association between interpersonal violence exposure and utilization of alcohol treatment after medical hospitalizations among adults with alcohol dependence. We analyzed data collected from a prospective cohort of 238 adults with alcohol dependence who were inpatients in a large urban hospital. Participants who reported interpersonal violence victimization had 1.6 times the odds (adjusted odds ratio = 1.64, 95% confidence interval = 0.92-2.91) of receiving alcohol treatment during the year after hospitalization compared to participants with no violence exposure. Recent (past 3 months) exposure to violence was not more strongly related to receipt of treatment than any lifetime violence exposure. Results suggest that a history of interpersonal violence victimization may be associated with an increased odds of alcohol treatment utilization following a medical hospitalization. Therefore, clinicians should be optimistic about identifying and referring patients who have experienced interpersonal violence to alcohol treatment. Moreover, given the potentially high prevalence of interpersonal violence exposure among inpatient populations at large urban hospitals, alcohol treatment providers should develop methods to address both alcohol dependence and violence recovery. PMID- 17869053 TI - NF-kappaB activation as a key mechanism in ethanol-induced disruption of the F actin cytoskeleton and monolayer barrier integrity in intestinal epithelium. AB - Intestinal barrier disruption has been implicated in several intestinal and systemic disorders including alcoholic liver disease (ALD). Using monolayers of intestinal (Caco-2) cells, we showed that ethanol (EtOH) disrupts the barrier integrity via destabilization of the cytoskeleton. Because proinflammatory conditions are associated with activation of NF-kappa B (NF-kappaB), we hypothesized that EtOH induces disruption of cytoskeletal assembly and barrier integrity by activating NF-kappaB. Parental cells were pretreated with pharmacological modulators of NF-kappaB. Other cells were stably transfected with a dominant negative mutant for the NF-kappaB inhibitor, I-kappaBalpha. Monolayers of each cell type were exposed to EtOH and we then monitored monolayer barrier integrity (permeability); cytoskeletal stability and molecular dynamics (confocal microscopy and immunoblotting); intracellular levels of the I-kappaBalpha (immunoblotting); subcellular distribution and activity of NF-kappaB (immunoblotting and sensitive ELISA); and intracellular alterations in the 43kDa protein of the actin cytoskeleton, polymerized F-actin, and monomeric G-actin (SDS-PAGE fractionation). EtOH caused destabilizing alterations, including I kappaBalpha degradation, NF-kappaB nuclear translocation, NF-kappaB subunit (p50 and p65) activation, actin disassembly (upward arrow G-, downward arrow F-), actin cytoskeleton instability, and barrier disruption. Inhibitors of NF-kappaB and stabilizers of I-kappaBalpha (e.g., MG-132, lactacystin, etc) prevented NF kappaB activation while protecting against EtOH-induced injury. In transfected I kappaBalpha mutant clones, stabilization of I-kappaBalpha to inactivate NF-kappaB protected against all measures of EtOH-induced injury. Our data support several novel mechanisms where NF-kappaB can affect the molecular dynamics of the F-actin cytoskeleton and intestinal barrier integrity under conditions of EtOH injury. (1) EtOH induces disruption of the F-actin cytoskeleton and of intestinal barrier integrity, in part, through I-kappaBalpha degradation and NF-kappaB activation; (2) The mechanism underlying this pathophysiological effect of the NF-kappaB appears to involve instability of the assembly of the subunit components of actin network. PMID- 17869054 TI - The S-shaped orthotopic ileal neobladder substitute incorporating a new seromuscular antireflux technique (split ileal end) in a series of 50 patients. AB - OBJECTIVE: The purpose of this study was to assess the function of our new technique, complications, continence, voiding patterns in those patients with the clinical evaluation of the S-shaped orthotopic ileal neobladder substitute incorporating a new antireflux technique. PATIENTS AND METHODS: Between April 2002 and November 2006, 50 patients (44 men and 6 women) underwent radical cystectomy and S-shaped ileal neobladder reconstruction with our new antireflux technique (split seromuscular). The mean age of male patients was 58 years (45-71 years). The mean age of female patients was 50 years (45-55 years). In all patients an S-shaped ileal pouch was constructed incorporating the new antireflux technique. This antireflux has not yet been described in the literature before. All procedures are performed by the same surgeons and the mean follow-up was 30 months. Complications were registered as early (occurring within 3 months) or late (occurring after 3 months), and as diversion-related and diversion unrelated. Continence and voiding patterns were also evaluated. RESULTS: There is no reflux in all patients except one. Early complications occurred in 8 patients. The most common early diversion-related complication was urinary leakage in 3 patients. No patients sustained an early diversion-related complication attributed to the new antireflux technique. Late complications occurred in 6 patients. Overall, 39 patients voided to completion without needing catheterization. A total of 7 patients required some form of clean intermittent catheterization to empty the new bladder completely including 5 of 44 men (12.5%) and 2 of 6 women (33.3%). CONCLUSIONS: The functional results with this pouch incorporating the new antireflux technique were efficient. Our S-shaped pouch has reduced the length of intestine (37 cm) that minimized the metabolic and malabsorption complications. Moreover it is simple. PMID- 17869055 TI - Effects of mixing metal ions on oxidative DNA damage mediated by a Fenton-type reduction. AB - The formation of 8-hydroxy-deoxyguanosine (8-OHdG) and strand breaks in DNA by Fenton-type reactions by mixtures of two of five metal ions, iron (II), cadmium (II), nickel (II), chromium (III) or copper (II), has been investigated and compared to their formation by each single metal ion. Salmon sperm DNA and pBluescript K+ plasmid were each incubated with hydrogen peroxide and metal ions. The formation of 8-OHdG declined in the Fe (II) or Cu (II) Fenton reaction upon addition of Cd (II) or Ni (II) ion. In contrast, the Fe (II) reaction upon addition of Cr (III) ion showed an additive influence on the formation of 8-OHdG. Furthermore, the Cu (II) plus Cr (III) reaction showed a synergistic effect. These influences relate to the interaction of metal ions with DNA, the potentials of the metal ions to generate activated oxygen and electron transfer between metal ions. The formation of DNA strand breaks was investigated in plasmid DNA by agarose gel electrophoresis and subsequent densitometry. The formation of DNA strand breaks in the Fe (II) or Cu (II) Fenton reaction decreased upon the addition of Ni (II) ion, as with the formation of 8-OHdG mediated by these metal ions. On the other hand, the formation of DNA strand breaks in the Fe (II) reaction decreased upon addition of Cr (III) ion, and the Cu (II) plus Cr (III) reaction did not show the synergistic influence on DNA strand breaks. These results suggest that interactions between two metal ions can influence the generation of 8-OHdG and the formation of DNA strand breaks and demonstrate that these lesions can arise by different mechanisms. PMID- 17869056 TI - A confirmatory factor analysis of specific phobia domains in African American and Caucasian American young adults. AB - The current study investigated factors related to specific phobia domains and differences in patterns among African American and Caucasian American adults. Subjects were 100 African Americans and 121 Caucasian Americans who completed the Fear Survey Schedule--Second Edition (FSS-II). Fears related to specific phobia domains were first examined, with frequencies differing between African American and Caucasian American samples on three of the six specific phobia domains. A confirmatory factor analysis was conducted to determine the patterns of specific phobias among the African American sample. The trimmed model for the African American sample included natural environment, animal and social anxiety specific phobia factors as latent, exogenous variables. Data from the Caucasian American sample provided a poor fit to this model. Instead, the trimmed model for the Caucasian American sample included the situational, animal and social anxiety factors. The natural environment-type specific phobia factor did not have adequate fit for the Caucasian American sample as in the African American sample. Results indicated that different factor loading patterns of fear-related stimuli may exist among African American and Caucasian American young adults. Potential explanations and future directions are discussed. PMID- 17869057 TI - Stimulus-evoked glutamate release is diminished by acute exposure to uranium in vitro. AB - Uranium is used in civilian applications, in the manufacture of nuclear fuel, and by the military for munitions and armament, but little information is available on its neurotoxicity. Neurological dysfunctions have been observed after chronic exposure in both animals and humans, but the actions of acute exposure on amino acid neurotransmission have not been investigated. The following study was performed to examine the effects of uranyl ion (UO(2)(+2)) on hippocampal glutamatergic and GABAergic function as possible bases for the neurotoxicity and to assess the direct effects on the exocytotic process. Nominal UO(2)(+2) concentrations were applied to superfused hippocampal synaptosomes to permit estimation of the metal's potency on endogenous transmitter release in the presence and absence of Ca(+2). K(+)-evoked glutamate release was diminished in the range of 10 nM-316 microM UO(2)(+2), resulting in an IC(50) of 1.92 microM. In contrast, the potency of UO(2)(+2) to decrease stimulated GABA release was reduced, producing an IC(50) approximately 2.6 mM. In the absence of Ca(+2) in the superfusion medium there was no systematic change in the magnitude of glutamate or GABA release, suggesting that UO(2)(+2) does not possess Ca(+2) mimetic properties. The inhibitory potency of UO(2)(+2) on glutamate release is similar to the potencies of other multivalent metal ions, suggesting by inference an action exerted on voltage-sensitive Ca(+2) channels. The bases for the reduced potency to inhibit GABA release is not known, but differential sensitivity to other heavy metals has been reported for glutamate and GABA neurotransmission. These findings indicate a profile of neurotoxicity not unlike that of other metal ions, and indicate the importance of extending subsequent studies to chronic exposure models. PMID- 17869058 TI - Quantitative assessment of pulmonary insufficiency by Doppler echocardiography in patients with adult congenital heart disease. AB - We determined the utility of continuous wave (CW) Doppler for quantification of pulmonary insufficiency (PI) confirmed by pulmonary angiography in patients with postoperative adult congenital heart disease. A total of 41 patients with PI were divided into two groups on the basis of PI severity by pulmonary angiography: group A (n = 27) with severe PI and group B (n = 14) with mild or moderate PI. Nine patients in group A had pulmonic valve replacement and reverted to mild PI after surgery. Their pre- and postoperative data were compared. All underwent a two-dimensional/Doppler study with interrogation of the PI jet for jet width by color Doppler and peak flow velocity, deceleration time (DT), pressure half-time (PHT), diastolic period (DP), and PI flow time (FT) by CW Doppler. The no-flow time (NFT), NFT/FT ratio, and NFT/DP fraction were calculated. Group A had a larger right ventricle (4.1 +/- 0.9 vs. 3.5 +/- 0.6 cm, P = .033), higher PI peak velocity (2.1 +/- 0.5 vs. 1.7 +/- 0.5 m/s, P = .04), shorter DT (261 +/- 61 vs. 317 +/- 83 ms, P = .018) and PHT (76 +/- 29 vs. 132 +/- 53, P < .0001), longer NFT (146 +/- 66 vs. 40 +/- 42 ms, P < .0001), and higher ratios of NFT/FT (46% +/ 27% vs. 13% +/- 14%, P < .0001) and NFT/DP (29% +/- 13% vs. 10% +/- 9%, P < .0001). The PHT and DT lengthened, and the NFT shortened in patients who underwent pulmonic valve replacement (all P < .05). By binary logistic regression, NFT and PHT were the best predictors for severe PI. An NFT of 80 ms had 84% sensitivity and 93% specificity, and a PHT of 100 ms had 93% sensitivity and 93% specificity for identifying angiographically severe PI. CW Doppler accurately distinguishes severe from lesser degrees of PI in patients with postoperative adult congenital heart disease. PMID- 17869060 TI - Severe aortic regurgitation after repair of ruptured sinus of Valsalva aneurysm: the role of transesophageal echocardiography. AB - We report a 27-year-old woman who presented with worsening exertional dyspnea and palpitation. Transthoracic echocardiography showed ventricular septal defect, with left-to-right shunting and mild aortic regurgitation detected. Cardiac catheterization was performed that revealed sinus of Valsalva aneurysm with rupture into the right ventricle. Transesophageal echocardiography (TEE) confirmed a rupture of sinus of Valsalva aneurysm and ventricular septal defect. The patient underwent elective surgical repair of the ruptured sinus and intraoperative TEE demonstrated severe aortic regurgitation after repair and mechanical prosthetic valve was implanted. This case illustrates that TEE frequently establishes the diagnosis and provides more information concerning additional cardiac lesions in a patient with ruptured sinus of Valsalva aneurysm. Aortic regurgitation should be evaluated after repair of rupture of sinus of Valsalva by TEE. PMID- 17869061 TI - An unusual cause of severe mitral regurgitation: aberrantly inserted chordae tendineae. AB - We present a case of aberrantly inserted chordae tendineae causing severe mitral regurgitation and requiring surgical correction. This is an extremely rare finding illustrating a distinct mechanism of mitral regurgitation. PMID- 17869062 TI - Increased plasma aldosterone-to-renin ratio is associated with impaired left ventricular longitudinal functional reserve in patients with uncomplicated hypertension. AB - Relative aldosterone excess is associated with endothelial dysfunction and higher incidence of end organ damage. We sought to investigate whether plasma aldosterone-to-renin ratio (ARR) is associated with left ventricular (LV) longitudinal function reserve to exercise in patients with controlled hypertension. In the patients with controlled and uncomplicated hypertension without overt LV hypertrophy, plasma aldosterone concentrations (ng/dL) and renin activities (ng/mL/h) were measured. Then 28 consecutive patients with higher ARR (group II, ARR > or = 30, 55 +/- 10 years) and 56 age- and sex-matched patients with lower ARR (group I, ARR < 30) underwent supine bicycle exercise echocardiography. Despite similar 24-hour blood pressure, LV mass index was significantly higher in group II (91.1 +/- 16.4 vs 101.7 +/- 18.2 g/m(2), P = .008). Early diastolic and systolic mitral annular velocity (E' and S', cm/s) at 50-W exercise was significantly lower in group II compared with group I (9.91 +/- 1.66 vs 8.67 +/- 1.65 cm/s, P = .002; 9.52 +/- 1.71 vs 8.46 +/- 1.79, P = .010, respectively) despite similar resting values. Longitudinal diastolic functional reserve at 25-W and 50-W exercise, defined as DeltaE' (change from resting E', cm/s) of group II was significantly lower than that of group I (2.60 +/- 1.42 vs 1.85 +/- 1.44 cm/s, P = .016; 3.40 +/- 1.48 vs 2.36 +/- 1.43 cm/s, P = .003, respectively). In conclusion, in patients with hypertension without overt LV hypertrophy, increased ARR is associated with increased LV mass, and impaired LV longitudinal functional reserve during exercise. PMID- 17869063 TI - Myocardial radial strain in early diastole is useful for assessing left ventricular early diastolic function: comparison with invasive parameters. AB - BACKGROUND: Peak myocardial systolic strain determined using myocardial strain imaging is a useful index of left ventricular (LV) myocardial systolic function. We investigated the relationship between peak myocardial radial strain during early diastole and LV early diastolic function. METHODS: A total of 85 patients without localized LV wall-motion abnormality underwent myocardial strain imaging and diagnostic cardiac catheterization. Peak myocardial radial strain during early diastole was obtained at the LV posterior-sided wall in the short-axis image. Invasive parameters of LV function were determined during cardiac catheterization. RESULTS: Peak myocardial radial strain during early diastole significantly correlated with both the time constant tau (r = 0.80, P < .0001) and the peak negative dP/dt (r = -0.64, P < .0001). Although it correlated with the LV ejection fraction, LV end-diastolic pressure, LV end-systolic volume index, and mean pulmonary capillary wedge pressure, the time constant tau was the prime determinant of peak myocardial radial strain during early diastole. CONCLUSION: Peak myocardial radial strain during early diastole could be used to evaluate LV early diastolic function. Myocardial strain imaging is a promising noninvasive tool for assessing LV function in systole and early diastole. PMID- 17869064 TI - Afterdischarges during cortical stimulation at different frequencies and intensities. AB - PURPOSE: The occurrence of unwanted afterdischarges (ADs) impedes cortical stimulation for mapping purposes. We investigated the safety of several stimulation paradigms. METHODS: We compared the incidence of ADs and behavioral responses of two stimulation frequencies (50 and 100 Hz), at two intensities (1 and 0.2 ms pulse widths). RESULTS: Stimulation with 100 Hz was more likely to cause ADs than 50 Hz, and stimulation using 1 ms pulse width was more likely to cause ADs than 0.2 ms. CONCLUSIONS: Stimulation using 50 Hz frequency with a pulse width of 0.2 ms might be safer during cortical mapping. PMID- 17869065 TI - Orienting of attention in unmedicated patients with schizophrenia, prodromal subjects and healthy relatives. AB - In typical orienting of attention tasks subjects have to respond as fast as possible to targets which appear in the periphery of the visual field and are preceded by spatial cues (e.g. brightening of a peripheral box where the target may subsequently appear). Reaction times (RT) are facilitated when cue and target appear at the same location (valid cueing) and the cue target interval is short (<250 ms). However, RTs slow down again when the target follows a valid cue after an interval of 250 ms and longer. This latter phenomenon is called Inhibition of Return (IOR) and is thought to reflect an automatic, inhibitory mechanism to protect the organism from redundant and distracting stimuli. Deficits of IOR were repeatedly reported in patients with schizophrenia. However, the role of medications and the nature of the deficit (trait or vulnerability indicator?) were unclear. In the present study we examined 15 unmedicated patients with schizophrenia (age: 31.2+/-11.1, m/f: 11/4, global scores SAPS: 48.33+/-33.09, SANS: 19.22+/-26.16), 29 subjects who were putatively in a prodromal state of psychosis, 30 first-degree relatives, another 8 first-degree relatives who had one child and at least one more relative with schizophrenia, and 50 healthy controls. We found an impairment of IOR only in the unmedicated patient group. In conclusion, blunted IOR in schizophrenia is not secondary to medications. According to this and previous studies blunted IOR may be most probably viewed as a trait cognitive feature of the schizophrenic disorder. PMID- 17869067 TI - Isolation, characterization and complete nucleotide sequence of a novel temperate bacteriophage Min1, isolated from the nematode pathogen Microbacterium nematophilum. AB - We report the discovery, properties and complete sequence (46,365bp) of Min1, the first bacteriophage to be reported for the coryneform genus Microbacterium. This temperate phage is normally integrated into a stable plasmid, pMN1, found in cells of Microbacterium nematophilum, a pathogen of certain soil nematodes including Caenorhabditis elegans, but it can also grow lytically. The phage is lambdoid in morphology and in sequence, belonging to the family Siphoviridae. General and specific features of the genome are discussed, together with possible contributions of the phage to host virulence. PMID- 17869066 TI - Nonsense mutations in the hairless gene underlie APL in five families of Pakistani origin. AB - BACKGROUND: Atrichia with papular lesions (APL) is a rare autosomal recessive form of inherited alopecia. Affected individuals present with a distinct pattern of total hair loss on the scalp, axilla and body shortly after birth and are essentially devoid of eyelashes and eyebrows. This form of hair loss is irreversible and the histology is consistent with an absence of mature hair follicles. In addition to total atrichia, APL patients also present with papules and follicular cysts filled with cornified material. Mutations in the Hairless (HR) gene have been shown to underlie APL. OBJECTIVE: Here, we studied five unrelated large Pakistani families with clinical manifestations of APL. METHODS: Based on previous reports of HR mutations in APL, we performed direct DNA sequencing analysis. RESULTS: DNA sequencing of the HR gene in APL patients revealed three novel nonsense mutations in five unrelated families. All affected individuals were homozygous for a nonsense mutation due to C-to-T transitions at different positions in the amino acid sequence. Two families carry the mutation Q323X (CAG-TAG) in exon 3, two families harbor the mutation Q502X (CAG-TAG) in exon 6, and one family had a mutation at R940X (CGA-TGA) in exon 14. Haplotype analysis revealed that all affected individuals of both APL1 and APL16 families were homozygous for the same haplotype, and likewise, the mutation in families APL2 and APL19 was on the same haplotype. CONCLUSIONS: We report three novel nonsense mutations in the HR gene in APL. Two of the newly identified mutations, Q323X and Q502X, were found to be shared between unrelated families and marker analysis confirmed an identical homozygous haplotype for APL1 and APL16, and for APL2 and APL19. These findings suggest that Q323X and Q502X did not arise independently, but instead appear to have been propagated in the population. Collectively, these findings contribute further evidence for the involvement of hairless mutations in papular atrichia. PMID- 17869068 TI - Molecular typing of Staphylococcus aureus clinical isolates by pulsed-field gel electrophoresis, staphylococcal cassette chromosome mec type determination and dissemination of antibiotic resistance genes. AB - Pulsed-field gel electrophoresis (PFGE) of SmaI macrorestriction fragments of genomic DNA as well as staphylococcal cassette chromosome mec (SCCmec) typing for mecA-carrying isolates were used to study the distribution of clonal types among 177 Staphylococcus aureus clinical isolates recovered in a Spanish hospital between 2000 and 2003. Five major clonal types (P1 to P5) were identified by PFGE, with one of them (P1) comprising the majority of strains (47.5%). According to SCCmec typing, SCCmec type IVA was the most prevalent type, showing increasing prevalence in the hospital setting with respect to other pandemic clones. One SCCmec pattern was detected in different PFGE types, which demonstrates that the latter is a major discriminative typing method. Three novel SCCmec elements or variants were found, each in a different PFGE type. Oxacillin (methicillin) resistant and -susceptible S. aureus (MRSA and MSSA, respectively) strains were detected showing identical PFGE patterns, suggesting horizontal transfer of mecA to MSSA and/or mecA deletion from MRSA. Persistence of several S. aureus clones throughout the years within the same hospital environment was also observed. PMID- 17869069 TI - Infection of intravascular prostheses: how to treat other than surgery. AB - Long-term antimicrobial therapy may be effective in some patients with intravascular prosthesis infection. However, this approach does not represent an alternative to surgery when this is feasible, but is merely the best opportunity for patients too ill to tolerate a re-intervention. Prosthetic valve endocarditis may be treated with antibiotic therapy alone in selected patients who are haemodynamically stable with non-staphylococcal infections and no para-valvular complications. In contrast, infections of pacemaker leads or other implantable cardiac devices require complete hardware removal, as infection recurrence always occurs, even after a seemingly effective initial treatment. Attempts to treat conservatively infections of abdominal aortic grafts can be successful in a few cases, provided the patient is stable, the pathogen has been identified, and antibiotic susceptibility has been demonstrated. Treatment requires at least 4-6 weeks and may be followed by a sequential oral regimen once the acute phase of the infection has subsided. The correct duration of this treatment is often unknown and relapses are common after treatment withdrawal. The availability of novel antibacterial and antifungal agents - showing fast microbicidal activity that includes biofilm micro-organisms - such as daptomycin and caspofungin, or having a wide antimicrobial spectrum, such as tigecycline, may increase the probability of long-standing suppression or even eradication of the infection in these particular subsets of inoperable patients. However, so far, very little experience is available on the efficacy and tolerability of these drugs in intravascular prosthesis infections. Controlled studies are lacking and difficult to plan. Well-designed prospective studies may help to establish guidelines and reach a multidisciplinary consensus on the optimal therapeutic approach, and are therefore awaited. PMID- 17869070 TI - Annexin V is directly involved in cystic fibrosis transmembrane conductance regulator's chloride channel function. AB - The cystic fibrosis transmembrane conductance regulator (CFTR) functions as a cAMP-activated chloride channel, which is regulated by protein-protein interactions. The extent to which CFTR is regulated by these interactions remains unknown. Annexin V is overexpressed in cystic fibrosis (CF), and given the functional properties of annexin V and CFTR we considered whether they are associated and if so whether this has implications for CFTR function. Using co immunoprecipitation and overlay experiments, we show that annexin V is associated with nucleotide-binding domain 1 (NBD1) of CFTR. Surface plasmon resonance (SPR) indicated different KD values in the absence and presence of both calcium and ATP, suggesting that this interaction is calcium- and ATP-dependent. Using an siRNA approach and overexpression, we showed that CFTR chloride channel function and its localization in the cell membranes were dependent on annexin V expression. We concluded that annexin V is necessary for normal CFTR chloride channel activity. Furthermore, we show that CFTR and annexin V are partially co distributed in normal epithelial cells in human bronchi. In conclusion, we show for the first time that annexin V is associated with CFTR and is involved in its function. PMID- 17869071 TI - Removal of lead and cadmium ions from aqueous solution by adsorption onto micro particles of dry plants. AB - In the present work, Pb(II) and Cd(II) ion adsorption onto inert organic matter (IOM) obtained from ground dried plants: Euphorbia echinus, Launea arborescens, Senecio anthophorbium growing in semi-arid zones of Morocco and Carpobrotus edulis as the Mediterranean plant has been studied. A suspension of plant deroed micro-particles adsorbs lead and cadmium present as ionic species, with a higher affinity for Pb(II). The kinetics and the maximum capacity adsorption depend on the type of plant as well as on the metal ions (atomic weight, ionic radius and electronegativity). The adsorption process is affected by various parameters such as contact time, solution volume to mass of plant particles ratio (m/V), particle size, solution pH and metal concentration. A dose of 25 g/l of adsorbent was optimal to obtain maximum adsorption of both metal ions. The maximum metal uptake was obtained with particles of organic matter of <50 microm. As to classical ionic adsorption phenomena, the adsorption of both metal ions increases with the increase of the initial concentration in the solution. For the two metal cations, the uptake efficiency of the studied plants ranged from: C. edulis>E. echinus>S. anthophorbium>L. arborescens, however, the differences are rather small. Two different waste water types (domestic and industrial) were tested and good results were obtained for removal of Pb(II) and Cd(II) at more than 90%. The removal of the metal and mineral ions waste water was observed for PO(4)(3-) at 88%, for NO(3)(-) at 96.5% and for metal ions (Pb(II), Cd(II), Cu(II) and Zn(II)) at about 100%, using IOM as absorbent. PMID- 17869072 TI - A multi-approaches-guided genetic algorithm with application to operon prediction. AB - OBJECTIVE: The prediction of operons is critical to the reconstruction of regulatory networks at the whole genome level. Multiple genome features have been used for predicting operons. However, multiple genome features are usually dealt with using only single method in the literatures. The aim of this paper is to develop a combined method for operon prediction by using different methods to preprocess different genome features in order for exerting their unique characteristics. METHODS: A novel multi-approach-guided genetic algorithm for operon prediction is presented. We exploit different methods for intergenic distance, cluster of orthologous groups (COG) gene functions, metabolic pathway and microarray expression data. A novel local-entropy-minimization method is proposed to partition intergenic distance. Our program can be used for other newly sequenced genomes by transferring the knowledge that has been obtained from Escherichia coli data. We calculate the log-likelihood for COG gene functions and Pearson correlation coefficient for microarray expression data. The genetic algorithm is used for integrating the four types of data. RESULTS: The proposed method is examined on E. coli K12 genome, Bacillus subtilis genome, and Pseudomonas aeruginosa PAO1 genome. The accuracies of prediction for these three genomes are 85.9987%, 88.296%, and 81.2384%, respectively. CONCLUSION: Simulated experimental results demonstrate that in the genetic algorithm the preprocessing for genome data using multiple approaches ensures the effective utilization of different biological characteristics. Experimental results also show that the proposed method is applicable for predicting operons in prokaryote. PMID- 17869073 TI - A multi-layered approach to protein data integration for diabetes research. AB - OBJECTIVE: Recent advances in high-throughput experimental techniques have enabled many protein-protein interactions to be identified and stored in large databases. Understanding protein interactions is fundamental to the advancement of science and medical knowledge, unfortunately the scale of the requires an automated approach to analysis. We describe our graph-mining techniques to identify important structures within protein-protein interaction networks to aid in human comprehension and computerised analysis. METHODS AND MATERIALS: We describe our techniques for characterizing graph type and associated properties which is constructed from data collated from the Human Protein Reference Database. Using random graph rewiring comparative techniques and cross-validation with other identification methods a further analysis of the identified essential proteins is presented to illustrate the accuracy of these measures. We argue for using techniques based upon graph structure for separating and encapsulating proteins based upon functionality. RESULTS: We demonstrate how rational Erdos numbers may be used as a method to identify collaborating proteins based solely upon network structure. Further, by using dynamic cut-off limit it demonstrates how collaboration subgraphs can be generated for each protein within the network, and how graph containment can be used as a means of identifying which of many possible graphs are likely to be actual protein complexes. The demonstration protein interaction network built for diabetes is found to be a scale-free, small world graph with a power-law degree distribution of interactions on nodes. These findings are consistent with many other protein interaction networks. PMID- 17869074 TI - Quantum dots - nano-sized probes for the exploration of cellular and intracellular targeting. AB - Nanoparticles emerged as promising tool in drug targeting, since, after appropriate modification, they are able to deliver their payload to specific sites, like tissues, cells, or even certain cellular organelles. In this context, the delivery of nanoparticles from the circulation into the target cells represents a crucial step. Here, model drug delivery systems such as quantum dots are ideal candidates to elucidate this process in more detail, since they provide outstanding features like a small and uniform size, unique optical properties for most sensitive detection and modifiable surfaces. Recent progress in the surface chemistry of quantum dots expanded their use in biological applications, reduced their cytotoxicity and rendered quantum dots a powerful tool for the investigation of distinct cellular processes, like uptake, receptor trafficking and intracellular delivery. In this review, we will not only describe the ideal attributes of QDs for biological applications and imaging but also their distinct specific and non-specific pathways into the cells as well as their intracellular fate. PMID- 17869075 TI - Regenerative capacity differs between micro- and macrovesicular hepatic steatosis. AB - INTRODUCTION: Independent of etiology, the hepatic microvesicular steatosis has a worse prognosis compared with macrovesicular steatosis. Proliferation compensates for apoptosis and reflects regenerative mechanisms following liver injury. It is unknown whether these two types of fatty liver have differences in regenerative capacity and apoptosis, which could have an impact on their prognosis. METHODS: Two groups of pigs were studied for 72 days under a protein-deficient diet. One group received only protein-deficient diet (n=6), the other was treated in addition to the diet with 6g ethanol/kg/day by means of a percutaneous intragastric catheter (n=6). The rate of proliferating and apoptotic hepatocytes was determined, respectively, by proliferation cell nuclear antigen (PCNA) and ISEL/TUNEL staining for apoptosis in liver biopsies with similar steatosis grade in pigs with micro- or macrovesicular fatty liver. RESULTS: The ethanol-treated group developed microvesicular steatosis, the other group developed macrovesicular steatosis. Proliferation index was significantly increased in macrovesicular in comparison with microvesicular steatosis (p<0.05). Apoptosis rate was similar in both groups. CONCLUSIONS: Regeneration, but not apoptosis rate differs between micro- and macrovesicular steatosis. The reduced regenerative capacity in microvesicular steatosis may contribute to the worse prognosis of this subtype of fatty liver disease. PMID- 17869076 TI - Copulatory mechanism in a sexually cannibalistic spider with genital mutilation (Araneae: Araneidae: Argiope bruennichi). AB - Genitalia are among the fastest evolving morphological traits as evidenced by their common function as diagnostic traits in species identification. Even though the main function of genitalia is the successful transfer of spermatozoa, the presence of diverse structures that are obviously not necessary for this suggests that genitalia are a target of sexual selection. The male genitalia of many spider species are extremely complex and equipped with numerous sclerites, plates and spines whose functions are largely unknown. Selection on male genitalia may be particularly strong in sexually cannibalistic spiders, where mating success of males is restricted to a single female. We investigated the copulatory mechanism of the sexually cannibalistic orb weaving spider Argiope bruennichi by shock freezing mating pairs and revealed a complicated interaction between the appendices and sclerites that make up the male gonopods (paired pedipalps). The plate that covers the female genital opening (scape) is secured between two appendices of the male genital bulb, while three sclerites that bear the sperm duct are unfolded and extended into the female copulatory opening. During copulation, females attack and cannibalise the male and males mutilate their genitalia in about 80% of cases. Our study demonstrates that (i) genital coupling is largely accomplished on the external part of the female genitalia, (ii) that the mechanism requires an interaction between several non-sperm-transferring structures and (iii) that there are two predetermined breaking points in the male genitalia. Further comparative work on the genus Argiope will test if the copulatory mechanism with genital mutilation indeed is an adaptation to sexual cannibalism or if cannibalism is a female counter adaptation to male monopolisation through genital plugging. PMID- 17869077 TI - The lipF promoter of Mycobacterium tuberculosis is upregulated specifically by acidic pH but not by other stress conditions. AB - The lipF gene of Mycobacterium tuberculosis has been implicated in pathogenesis and its promoter has been shown to be upregulated by acidic stress. To further define the acidic pH that upregulates the lipF promoter from M. tuberculosis and to establish that it is specifically upregulated by acid stress and not by other environmental stresses, promoter expression levels were measured under a variety of conditions. The conditions measured were pH, temperature, oxidative stress, and hypoxic stress. PMID- 17869078 TI - The two faces of the 15-lipoxygenase in atherosclerosis. AB - Chronic inflammation plays a major role in atherogenesis and understanding the role of inflammation and its resolution will offer novel approaches to interfere with atherogenesis. The 15(S)-lipoxygenase (15-LOX) plays a janus-role in inflammation with pro-inflammatory and anti-inflammatory effects in cell cultures and primary cells and even opposite effects on atherosclerosis in two different animal species. There is evidence for a pro-atherosclerotic effect of 15-LOX including the direct contribution to LDL oxidation and to the recruitment of monocytes to the vessel wall, its role in angiotensin II mediated mechanisms and in vascular smooth muscle cell proliferation. In contrast to the pro atherosclerotic effects of 15-LOX, there is also a broad line of evidence that 15 LOX metabolites of arachidonic and linoleic acid have anti-inflammatory effects. The 15-LOX arachidonic acid metabolite 15-HETE inhibits superoxide production and polymorphonuclear neutrophil (PMN) migration across cytokine-activated endothelium and can be further metabolized to the anti-inflammatory lipoxins. These promote vasorelaxation in the aorta and counteract the action of most other pro-inflammatory factors like leukotrienes and prostanoids. Anti-atherogenic properties are also reported for the linoleic acid oxidation product 13-HODE through inhibition of adhesion of several blood cells to the endothelium. Furthermore, there is evidence that 15-LOX is involved in the metabolism of the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) leading to a family of anti-inflammatory resolvins and protectins. From these cell culture and animal studies the role of the 15-LOX in human atherosclerosis cannot be predicted. However, recent genetic studies characterized the 15-LOX haplotypes in Caucasians and discovered a functional polymorphism in the human 15-LOX promoter. This will now allow large studies to investigate an association of 15-LOX with coronary artery disease and to answer the question whether 15-LOX is pro- or anti atherogenic in humans. PMID- 17869079 TI - Intravenous magnesium sulphate provides no additive benefit to standard management in acute asthma. AB - BACKGROUND: Treatment of acute asthma is based on rapid reversal of bronchospasm and airway inflammation. Magnesium sulphate (MgSO(4)) is known to have a bronchodilator effect on smooth muscle but studies have shown conflicting results on its efficacy in acute asthma, although its use is recommended in national and international guidelines. AIMS: To determine if intravenous MgSO(4), when used as an adjunct to standard therapy, improves the outcome in acute asthma. METHODS: A double blind, randomised placebo controlled trial comparing 1.2g MgSO(4) with standard therapy in adult patients with acute asthma. Patients had a PEF 5cm) 62.8%, 40.3%, 0%, respectively. Survival of patients treated with PRFA was dependent on tumor size (p<0.001; risk ratio [RR] 9.6, 95% CI 5.2-17.8), number of tumors (p=0.003; RR 1.6, 95% CI 1.2-2.0), combination with PEI (p=0.01; RR 0.6, 95% CI 0.4-0.9), Child-Pugh class (p=0.002; RR 2.0, 95% CI 1.3-3.0) and safety margin (p=0.0026; RR 0.6, 95% CI 0.4-0.9). CONCLUSIONS: PRFA is an effective treatment for HCC. This study showed after PRFA, tumor size, number of tumors, combination with PEI, safety margin, and Child-Pugh class were independent risk factors of survival. PMID- 17869097 TI - Microbial protein production in activated suspension tanks manipulating C:N ratio in feed and the implications for fish culture. AB - The present experiment investigated the possibility of microbial protein production in 250 l indoor tanks by manipulating C:N ratio in fish feed applied. Two different levels of protein feed (35% and 22% CP) resulting in C:N ratio of 8.4 and 11.6, respectively, were applied at 25 g daily in each tank. Tanks were aerated and agitated continuously using a dome diffuser. The experiment was carried out for eight weeks. The biofloc development in terms of VSS and BOD5 was better in the low protein fed tanks than in the high protein fed tanks. An estimated biofloc productivity ranged 3-5 g Cm(-3)day(-1). A 3-D image stained with DAPI indicates that the biofloc is comprised of hundreds of bacterial nuclei, size being ranged from 100 to 200 microm. Biofloc quality was independent of the quality of feed applied and contained more than 50% crude protein, 2.5% crude lipid, 4% fibre, 7% ash and 22 kJ g(-1) energy on dry matter basis. The dietary composition and size of biofloc can be considered as appropriate for all omnivorous fish species. The underlying ecological processes are explained through factor analysis. The potential of using biofloc in fish culture is also discussed. PMID- 17869098 TI - A novel class of Hsp90 inhibitors isolated by structure-based virtual screening. AB - A novel class of 3-phenyl-2-styryl-3H-quinazolin-4-one Hsp90 inhibitors with in vitro anti-tumor activity are identified by structure-based virtual screening of a chemical database with docking simulations in the N-terminal ATP-binding site, in vitro ATPase assay using yeast Hsp90, and cell-based Her2 degradation assay in a consecutive fashion. These results exemplify the usefulness of the structure based virtual screening with molecular docking in drug discovery. The structural features responsible for a tight binding of the inhibitors in the active site of Hsp90 are discussed in detail. PMID- 17869099 TI - Novel orally active, dibenzazepinone-based gamma-secretase inhibitors. AB - Structural modifications of the gamma-secretase inhibitor, LY411575, led to a malonamide analogue (S),(S)-1 with potent inhibitory activity in vitro, but disappointing activity in a mouse model of Alzheimer's disease. Identification and replacement of a metabolically labile position provided an improved compound (R/S),(S)-13 with high in vitro activity (IC(50)=1.7 nM), and in vivo activity after oral administration (MED=3 mg/kg). Further modifications gave an equipotent carbamate analogue 14 with improved molecular properties. PMID- 17869100 TI - Discovery, synthesis, and structure-activity studies of tetrazole based growth hormone secretagogues. AB - A novel class of Growth Hormone Secretagogues (GHS), based on a tetrazole template, has been discovered. In vitro SAR and in vivo potency within this new class of GHS are described. The tetrazole 9q exhibits good oral bioavailability in rats and dogs as well as efficacy following an oral 10 mg/kg dose in dogs. Solution and solid phase protocols for the synthesis of tetrazole based GHS have been developed. PMID- 17869101 TI - High dopamine transporter selectivity can be displayed by remarkably simple non nitrogen containing inhibitors. AB - A series of 2-(3,4-dichlorophenyl)-cyclopent-1-enyl carboxylic acid esters and amides were prepared and tested for binding to the DAT, SERT, and NET. The achiral compounds were easily attained and found to inhibit DAT binding with K(i) values ranging from 0.095 to 0.00003 mM. Among the compounds tested 2-(3,4 dichlorophenyl)-cyclopent-1-enyl carboxylic acid 2-methylphenyl ester was found to be highly selective with SERT/DAT>7000; NET/DAT>1700, K(i)=60 nM. PMID- 17869102 TI - Pentacyclic triterpenes. Part 5: synthesis and SAR study of corosolic acid derivatives as inhibitors of glycogen phosphorylases. AB - The synthesis and biological evaluation of corosolic acid derivatives and related compounds as inhibitors of rabbit muscle glycogen phosphorylase a is described. Within this series of compounds, 8 (IC(50)=7.31 microM), 12d (IC(50)=3.26 microM), and 12e (IC(50)=5.1 microM) exhibited more potent activities than the parent compound 1 (IC(50)=20 microM). SAR of these compounds is also discussed. PMID- 17869103 TI - Taxodistines A and B, abietane-type diterpenes from Taxodium distichum. AB - Two new abietane-type diterpenes, taxodistines A (1) and B (2), have been isolated by the guidance of inhibitory effect of tubulin polymerization from the fruits of Taxodium distichum and the structures were elucidated by using 2D NMR data. Taxodistine B (2) showed inhibition of tubulin polymerization. PMID- 17869104 TI - Discovery of potent T-type calcium channel blocker. AB - The intensive SAR study of 3,4-dihydroquinazoline series led to the most potent compound 10 (KYS05090: IC(50)=41+/-1 nM) against T-type calcium channel and its potency is nearly comparable to that of Kurtoxin. As a small organic molecule, this compound showed the highest blocking activity reported to date. PMID- 17869105 TI - Synthesis and biological evaluation of phenyl piperidine derivatives as CCR2 antagonists. AB - A series of phenyl piperidine derivatives possessing potent and selective CCR2 antagonist activity is reported. Structure-activity relationship (SAR) studies have established that incorporation of a second ring system adjacent to the aryl piperidine plays an important role in determining the CCR2 potency. Both a second piperidine ring and a 1,3-substituted cyclopentylamine have been probed as linkers. For the cyclopentylamine series, the 1S,3R-configuration exhibits much higher affinity for hCCR2 than the 1R,3S-configuration. Compound 3g shows good selectivity over CCR1, CCR3, 5-HT and has an excellent P450 profile. PMID- 17869106 TI - Pain in different methods of breast biopsy: emphasis on vacuum-assisted breast biopsy. AB - This study examines pain (visual analog scale 0-10) in women undergoing breast biopsy. Two hundred and twenty-seven patients with a palpable lesion underwent FNA (21G, n=85), core biopsy (14G, n=86) or open biopsy under local anesthesia (n=56). One hundred and twenty-six women presented with a non-palpable lesion, and underwent vacuum-assisted breast biopsy (VABB, 11G) under mammographic guidance, prone position (n=72) or hook-wire localization followed by open surgery (n=54). The techniques sampling non-palpable lesions were the most painful: hook-wire (9.15+/-0.74) and VABB (4.35+/-1.70). Larger needle diameter was associated with more intense pain. Concerning VABB, an S-shape curve of pain (third-order pattern) was documented. A second dose of lidocaine just before the rapid increase phase was then adopted (n=61), and reduced the total/maximum pain. In conclusion, although VABB is less painful than hook-wire, the pain experienced in VABB is significant; however, it can be attenuated by a second dose of lidocaine. PMID- 17869107 TI - Radiolabelled somatostatin analogs for diagnosis and radio-guided surgery of neuroendocrine breast cancer undetectable with conventional imaging procedures. AB - Some neoplasms are classified as primary neuroendocrine tumours (NETs) because of their positivity for neuroendocrine markers [chromogranins A and B (CgA, CgB) and neuron-specific enolase (NSE)]. Neuroendocrine differentiation has been reported, for example, in both "in situ" and infiltrating breast cancer. Diagnosis of NET is bio-humoral (CgA, NSE, synaptophysin) and instrumental. Even if the final diagnosis is made by open biopsy, radionuclide imaging using radiolabelled somatostatin analogs, such as In-111 pentetreotide, may detect neuroendocrine primary tumours and metastases before they become detectable using traditional and advanced imaging modalities [mammography (MX), ultrasound (US) and magnetic resonance imaging (MRI)]. When neuroendocrine breast lesions are not detectable, radio-guided surgery (RGS) is able to localise cancer. We report a case of a woman with a palpable lymph node in the left axilla. She underwent a US-guided lymph node biopsy, which was positive for massive metastases, probably of neuroendocrine breast origin. Mammary plus axillary US showed only lymphadenopathy in the left axilla. MX and breast MRI were negative. Neoplastic markers (CEA, CA 15.3, CA 125 and CA 19.9) were negative too. On the other hand, neuroendocrine markers (NSE and CgA) were positive. A whole body scintigraphic scan plus thorax and abdomen single photon emission computed tomography (SPECT) with In-111 pentetreotide (222 MBq; 6 mCi) showed an uptake in the left mammary gland. No other pathological localisations were observed. The day after the intravenous injection of In-111 pentetreotide, the patient underwent RGS breast tumour resection and left axillary lymphadenectomy. In conclusion, we would like to emphasise: (1) the role of radionuclide imaging for the detection of breast NETs in relation to conventional diagnostic procedures; (2) the role of RGS in localising and removing a non-palpable breast NET that was undetectable with the use of conventional imaging techniques. PMID- 17869108 TI - Equivalent parental contribution to early plant zygotic development. AB - Hybrid vigor or heterosis results from the combination of genetically distant genomes at fertilization, and as well as being of major commercial importance, it is held to contribute significantly to fitness [1]. Activation of the paternal genome marks the transition from maternal to zygotic control of development, but a reported delay of paternal-genome activation in flowering plants [2-4] and animals [5, 6] excludes heterosis from impacting on very early development. We have analyzed the allele-specific expression of 25 genes after fertilization of the egg in maize and show immediate equivalent parental genomic contribution to the zygote. Every gene expressed before the first cell division of the zygotes showed paternal transcripts. Sequence comparisons indicate that these genes are involved in a range of processes and are distributed throughout the genome. Our findings confirm that some plant species have evolved a strategy to activate the paternal genome immediately after fertilization, in contrast to the situation in other plants and in animals. Such an extensive activation of the paternal genome very early in development is consonant with observations of high levels of heterosis in early hybrid maize embryos [7, 8], indicating a significant impact of this sexual strategy on fitness. PMID- 17869109 TI - The Polerovirus F box protein P0 targets ARGONAUTE1 to suppress RNA silencing. AB - Plants employ post-transcriptional gene silencing (PTGS) as an antiviral defense response. In this mechanism, viral-derived small RNAs are incorporated into the RNA-induced silencing complex (RISC) to guide degradation of the corresponding viral RNAs. ARGONAUTE1 (AGO1) is a key component of RISC: it carries the RNA slicer activity. As a counter-defense, viruses have evolved various proteins that suppress PTGS. Recently, we showed that the Polerovirus P0 protein carries an F box motif required to form an SCF-like complex, which is also essential for P0's silencing suppressor function. Here, we investigate the molecular mechanism by which P0 impairs PTGS. First we show that P0's expression does not affect the biogenesis of primary siRNAs in an inverted repeat-PTGS assay, but it does affect their activity. Moreover, P0's expression in transformed Arabidopsis plants leads to various developmental abnormalities reminiscent of mutants affected in miRNA pathways, which is accompanied by enhanced levels of several miRNA-target transcripts, suggesting that P0 acts at the level of RISC. Interestingly, ectopic expression of P0 triggered AGO1 protein decay in planta. Finally, we provide evidence that P0 physically interacts with AGO1. Based on these results, we propose that P0 hijacks the host SCF machinery to modulate gene silencing by destabilizing AGO1. PMID- 17869110 TI - The Polerovirus silencing suppressor P0 targets ARGONAUTE proteins for degradation. AB - Plant and animal viruses encode suppressor proteins of an adaptive immunity mechanism in which viral double-stranded RNA is processed into 21-25 nt short interfering (si)RNAs. The siRNAs guide ARGONAUTE (AGO) proteins so that they target viral RNA. Most viral suppressors bind long dsRNA or siRNAs and thereby prevent production of siRNA or binding of siRNA to AGO. The one exception is the 2b suppressor of Cucumoviruses that binds to and inhibits AGO1. Here we describe a novel suppressor mechanism in which a Polerovirus-encoded F box protein (P0) targets the PAZ motif and its adjacent upstream sequence in AGO1 and mediates its degradation. F box proteins are components of E3 ubiquitin ligase complexes that add polyubiquitin tracts on selected lysine residues and thereby mark a protein for proteasome-mediated degradation. With P0, however, the targeted degradation of AGO is insensitive to inhibition of the proteasome, indicating that the proteasome is not involved. We also show that P0 does not block a mobile signal of silencing, indicating that the signal molecule does not have AGO protein components. The ability of P0 to block silencing without affecting signal movement may contribute to the phloem restriction of viruses in the Polerovirus group. PMID- 17869111 TI - Dynamics of visual information integration in the brain for categorizing facial expressions. AB - A key to understanding visual cognition is to determine when, how, and with what information the human brain distinguishes between visual categories. So far, the dynamics of information processing for categorization of visual stimuli has not been elucidated. By using an ecologically important categorization task (seven expressions of emotion), we demonstrate, in three human observers, that an early brain event (the N170 Event Related Potential, occurring 170 ms after stimulus onset) integrates visual information specific to each expression, according to a pattern. Specifically, starting 50 ms prior to the ERP peak, facial information tends to be integrated from the eyes downward in the face. This integration stops, and the ERP peaks, when the information diagnostic for judging a particular expression has been integrated (e.g., the eyes in fear, the corners of the nose in disgust, or the mouth in happiness). Consequently, the duration of information integration from the eyes down determines the latency of the N170 for each expression (e.g., with "fear" being faster than "disgust," itself faster than "happy"). For the first time in visual categorization, we relate the dynamics of an important brain event to the dynamics of a precise information processing function. PMID- 17869112 TI - EGG-3 regulates cell-surface and cortex rearrangements during egg activation in Caenorhabditis elegans. AB - Fertilization triggers egg activation and converts the egg into a developing embryo. The events of this egg-to-embryo transition typically include the resumption of meiosis, the reorganization of the cortical actin cytoskeleton, and the remodeling of the oocyte surface. The factors that regulate sperm-dependent egg-activation events are not well understood. Caenorhabditis elegans EGG-3, a member of the protein tyrosine phosphatase-like (PTPL) family, is essential for regulating cell-surface and cortex rearrangements during egg activation in response to sperm entry. Although fertilization occurred normally in egg-3 mutants, the polarized dispersal of F-actin is altered, a chitin eggshell is not formed, and no polar bodies are produced. EGG-3 is associated with the oocyte plasma membrane in a pattern that is similar to CHS-1 and MBK-2. CHS-1 is required for eggshell deposition, whereas MBK-2 is required for the degradation of maternal proteins during the egg-to-embryo transition. The localization of CHS 1 and EGG-3 are interdependent and both genes were required for the proper localization of MBK-2 in oocytes. Therefore, EGG-3 plays a central role in egg activation by influencing polarized F-actin dynamics and the localization or activity of molecules that are directly involved in executing the egg-to-embryo transition. PMID- 17869113 TI - Regulation of MBK-2/Dyrk kinase by dynamic cortical anchoring during the oocyte to-zygote transition. AB - BACKGROUND: Successful transition from oocyte to zygote depends on the timely degradation of oocyte proteins to prepare for embryonic development. In C. elegans, degradation of the oocyte protein MEI-1 depends on MBK-2, a kinase that phosphorylates MEI-1 shortly after fertilization during the second meiotic division. RESULTS: Here we report that precise timing of MEI-1 phosphorylation depends on the cell cycle-regulated release of MBK-2 from the cortex. Prior to the meiotic divisions, MBK-2 is tethered at the cortex by EGG-3, an oocyte protein required for egg activation (see [1], accompanying paper in this issue). During the meiotic divisions, EGG-3 is internalized and degraded in an APC/C (anaphase-promoting complex/cyclosome)-dependent manner. EGG-3 internalization and degradation correlate with MBK-2 release from the cortex and MEI-1 phosphorylation in the cytoplasm. In an egg-3 mutant, MEI-1 is phosphorylated and degraded prematurely. CONCLUSION: We suggest that successful transition from an oocyte to a zygote depends on the cell cycle-regulated relocalization of key regulators from the cortex to the cytoplasm of the egg. PMID- 17869114 TI - Gait and balance of transfemoral amputees using passive mechanical and microprocessor-controlled prosthetic knees. AB - BACKGROUND: Microprocessor-controlled knee joints appeared on the market a decade ago. These joints are more sophisticated and more expensive than mechanical ones. The literature is contradictory regarding changes in gait and balance when using these sophisticated devices. METHODS: This study employed a crossover design to assess the comparative performance of a passive mechanical knee prosthesis compared to a microprocessor-controlled knee joint in 15 subjects with an above knee amputation. Objective measurements of gait and balance were obtained. RESULTS: Subjects demonstrated significantly improved gait characteristics after receiving the microprocessor-controlled prosthetic knee joint (p<0.01). Improvements in gait were a transition from a hyperextended knee to a flexed knee during loading response which resulted in a change from an internal knee flexor moment to a knee extensor moment. The participants' balance also improved (p<0.01). All conditions of the Sensory Organization Test (SOT) demonstrated improvements in equilibrium score. The composite score also increased. CONCLUSIONS: Transfemoral amputees using a microprocessor-controlled knee have significant improvements in gait and balance. PMID- 17869116 TI - MexAB-OprM specific efflux pump inhibitors in Pseudomonas aeruginosa. Part 7: highly soluble and in vivo active quaternary ammonium analogue D13-9001, a potential preclinical candidate. AB - A series of 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives, substituted at the 2 position with piperidines bearing quaternary ammonium salt side chains, were synthesized and evaluated for their ability to potentiate the activity of the fluoroquinolone levofloxacin (LVFX) and the beta-lactam aztreonam (AZT) in Pseudomonas aeruginosa. Attachment of the charged entity using an N ethylcarbamoyloxy linker led to the discovery of the highly soluble compound 22 (D13-9001), which maintained good potency in vitro and displayed excellent activity in vivo in a rat pneumonia model of P. aeruginosa. PMID- 17869115 TI - Novel analogs of D-e-MAPP and B13. Part 1: synthesis and evaluation as potential anticancer agents. AB - A series of novel isosteric analogs of the ceramidase inhibitors, (1S,2R)-N myristoylamino-phenylpropanol-1 (d-e-MAPP) and (1R,2R)-N-myristoylamino-4'-nitro phenylpropandiol-1,3 (B13), with modified targeting and physicochemical properties were designed, synthesized, and evaluated as potential anticancer agents. When MCF7 cells were treated with the analogs, results indicated that the new analogs were of equal or greater potency compared to the parent compounds. Their activity was predominantly defined by the nature of the modification of the N-acyl hydrophobic interfaces: N-acyl analogs (class A), urea analogs (class B), N-alkyl analogs (class C, lysosomotropic agents), and omega-cationic-N-acyl analogs (class D, mitochondriotropic agents). The most potent compounds belonged to either class D, the aromatic ceramidoids, or to class C, the aromatic N alkylaminoalcohols. Representative analogs selected from this study were also evaluated by the National Cancer Institute In Vitro Anticancer Drug Discovery Screen. Again, results showed a similar class-dependent activity. In general, the active analogs were non-selectively broad spectrum and had promising activity against all cancer cell lines. However, some active analogs of the d-e-MAPP family were selective against different types of cancer. Compounds LCL85, LCL120, LCL385, LCL284, and LCL204 were identified to be promising lead compounds for therapeutic development. PMID- 17869118 TI - Identification of a series of novel derivatives as potent HCV inhibitors by a ligand-based virtual screening optimized procedure. AB - This paper presents the results of a ligand-based virtual screening optimized procedure on 98 compounds which have been recently evaluated as inhibitors of genotype 1 HCV polymerase. First, quantitative structure-activity patterns are investigated for the selected compounds and then structural modifications are proposed to afford novel active patterns. An accurate and reliable QSAR model involving five descriptors that is able to predict successfully the HCV inhibitory potency against genotype 1 HCV polymerase is presented. Furthermore, the effects of various structural modifications on biological activity are investigated and biological activities of novel structures are estimated using the developed QSAR model. More specifically a search for optimized pharmacophore patterns by insertions, substitutions, and ring fusions of pharmacophoric substituents of the main building block scaffolds is described. The detection of the domain of applicability defines compounds whose estimations can be accepted with confidence. PMID- 17869117 TI - Structure-activity relationship studies of flavonoids as potent inhibitors of human platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2. AB - Human lipoxygenase (hLO) isozymes have been implicated in a number of disease states and have attracted much attention with respect to their inhibition. One class of inhibitors, the flavonoids, have been shown to be potent lipoxygenase inhibitors but their study has been restricted to those compounds found in nature, which have limited structural variability. We have therefore carried out a comprehensive study to determine the structural requirements for flavonoid potency and selectivity against platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2. We conclude from this study that catechols are essential for high potency, that isoflavones and isoflavonones tend to select against 12-hLO, that isoflavons tend to select against 15-hLO-1, but few flavonoids target 15-hLO-2. PMID- 17869119 TI - Synthesis and evaluation of chloromethyl sulfoxides as a new class of selective irreversible cysteine protease inhibitors. AB - The synthesis and biological evaluation of a new class of selective irreversible cysteine protease inhibitors is described. A set of amino acid based chloromethyl sulfoxides was prepared and they were found to inhibit irreversibly the cysteine protease papain. They were selective for cysteine proteases since no inhibition was found for the serine protease chymotrypsin. PMID- 17869120 TI - Synthesis and biological activities of quinazoline derivatives with ortho-phenol quaternary ammonium salt groups. AB - One phenol-quaternary ammonium salt derivative with a flexible linker and three derivatives with a quinazoline moiety are present. Their binding affinities for DNA are discussed and it is clearly demonstrated that this class of phenol quaternary ammonium salt derivatives could inhibit DNA transcription effectively. PMID- 17869121 TI - Synthesis and biological evaluation of non-peptide alpha(v)beta(3)/alpha(5)beta(1) integrin dual antagonists containing 5,6 dihydropyridin-2-one scaffolds. AB - Small constrained non-peptidic molecules consisting of a polyfunctionalized rigid core, carrying appendages corresponding to arginine and aspartic acid side chains, have been recently reported to be promising for drug development. In this work, the 5,6-dihydropyridin-2-one was envisaged as a scaffold to turn into potential integrin ligands, introducing a carboxylic acid and a basic appendage. The synthesis and the antiadhesion activity of a small library of peptidomimetics capable to recognize alpha(v)beta(3) and alpha(5)beta(1) integrins has been herein reported. PMID- 17869123 TI - Construction of polyamine-modified uridine and adenosine derivatives--evaluation of DNA binding capacity and cytotoxicity in vitro. AB - We here report the synthesis of the two polyamine-based nucleoside derivatives 5 {[bis-(3-aminopropyl)amino]acetamido-1-propynyl}uridine and 2-{[bis-(3 aminopropyl)amino]-acetamido-1-propynyl}adenosine. The various polyamine derivatives have been used in thermal melting analysis using DNA from herring testes, and in cellular studies using four different cell lines. The compounds were all found to be non-toxic, thus holding good promise for future use as siRNA building blocks. PMID- 17869122 TI - Alpha-diaminobutyric acid-linked hairpin polyamides. AB - A hairpin polyamide-chlorambucil conjugate linked by alpha-diaminobutyric acid (alpha-DABA) has been shown to have interesting biological properties in cellular and small animal models. Remarkably, this new class of hairpin polyamides has not been previously characterized with regard to energetics and sequence specificity. Herein we present a series of pyrrole-imidazole hairpin polyamides linked by alpha-DABA and compare them to polyamides containing the standard gamma-DABA turn unit. The alpha-DABA hairpins have overall decreased binding affinities. However, alpha-DABA polyamide-chlorambucil conjugates are sequence-specific DNA alkylators with increased specificities. Affinity cleavage studies of alpha-DABA polyamide EDTA conjugates confirmed their preference for binding DNA in a forward hairpin conformation. In contrast, an unsubstituted glycine-linked polyamide prefers to bind in an extended binding mode. Thus, substitution on the turn unit locks the alpha-DABA polyamide into the forward hairpin binding motif. PMID- 17869124 TI - Influence of 6 or 8-substitution on the antiviral activity of 3 phenethylthiomethylimidazo[1,2-a]pyridine against human cytomegalovirus (HCMV) and varicella-zoster virus (VZV). AB - The synthesis of original imidazo[1,2-a]pyridines bearing a phenethylthiomethyl side chain at the 3 position and a (hetero)aryl substituent on the 6 or 8 position, and their antiviral activities are reported. From the synthesized compounds, the 6-halogeno and 6-phenylimidazo[1,2-a]pyridine derivatives 4c-d and 5b were the most potent against human cytomegalovirus (CMV) and/or varicella zoster virus (VZV), whereas several other congeners (i.e., 5e, 5g, 5i, 5l, 5n, 5p, 5q, and 5t), while less potent, were equally or more selective in their inhibitory activity against both VZV and CMV. These compounds showed similar activity against thymidine kinase competent (TK(+)) and deficient (TK(-)) VZV strains, demonstrating a mechanism of action independent of the viral thymidine kinase. PMID- 17869125 TI - Unconjugated bilirubin differentially affects the redox status of neuronal and astroglial cells. AB - We investigated whether nerve cell damage by unconjugated bilirubin (UCB) is mediated by oxidative stress and ascertained the neuronal and astroglial susceptibility to injury. Several oxidative stress biomarkers and cell death were determined following incubation of neurons and astrocytes isolated from rat cortical cerebrum with UCB (0.01-1.0 microM). We show that UCB induces a dose dependent increase in neuronal death in parallel with the oxidation of cell components and a decrease in the intracellular glutathione content. Comparison of the results obtained in both cell types demonstrates that neurons are more vulnerable than astrocytes to oxidative injury by UCB, for which accounts the lower glutathione stores in neuronal cells. Moreover, neuronal oxidative injury is prevented by supplementation with N-acetylcysteine, a glutathione precursor, whereas astroglial sensitivity to UCB is enhanced by inhibition of glutathione synthesis, using buthionine sulfoximine. Collectively, we demonstrate that oxidative stress is involved in UCB neurotoxicity and depict a new therapeutic approach for UCB-induced oxidative damage. PMID- 17869126 TI - Creation of aorto-pulmonary window with pulmonary artery band is not good palliation for hypoplastic left heart syndrome. AB - OBJECTIVE: A small sub-group of patients with hypoplastic left heart syndrome (HLHS) have normal-sized ascending aorta and arch. An alternative to the Norwood I procedure in these patients is the creation of an aorto-pulmonary (AP) window with a distal pulmonary artery band (PAB). We reviewed our experience with this technique and compared outcomes to the Norwood procedure for HLHS. METHODS: All patients treated for HLHS in a single institution between 1992 and 2005 were analysed. This identified 13 patients treated with AP window and PAB compared to 333 patients undergoing stage I Norwood procedure. An unrestrictive AP window was created and the main PA was banded. Patient records and echocardiograms were analysed. Median follow-up was 10 (IQR 0-655) days and 100% complete. RESULTS: There were seven early deaths (54%) in the AP window group and two conversions to Norwood circulation. This was a significantly worse outcome than for the Norwood procedure over the same period, which had an early mortality of 29% (p=0.03). Kaplan-Meier actuarial analysis demonstrated a continued survival benefit of the Norwood group at 6 months (p=0.0005). Deaths were due to either low cardiac output syndrome (n=4) or sudden unheralded arrest (n=3). This occurred despite aortic cross-clamp and circulatory arrest times being significantly lower in the AP window group compared to the Norwood group (35+/-27 vs 55+/-16 min, p<0.01 and 16+/-29 vs 55+/-20 min, p<0.01, respectively). No differences in arterial saturations or systolic blood pressure existed between the groups, but diastolic blood pressure was significantly lower in the AP window group at 27+/-10 mmHg compared to 42+/-8 mmHg in the Norwood group (p=0.01) with evidence of flow reversal in the descending aorta. Differences in diastolic blood pressure between groups were abolished after conversion to stage II. CONCLUSIONS: Despite favourable anatomy and shorter ischaemic times, the AP window/PAB technique has a poor outcome compared to the Norwood procedure for HLHS. Low diastolic blood pressure with reversal of descending aortic flow in diastole was a feature of the AP window/PAB circulation. We recommend the Norwood procedure for these sub types. This may have implications for newer 'hybrid' procedures for HLHS which create a similar palliative circulation. PMID- 17869127 TI - Interleukin-6 -174 promoter polymorphism does not influence IL-6 production after LPS and IL-1 beta stimulation in human umbilical cord vein endothelial cells. AB - The IL-6 is a typical pleiotropic cytokine, which regulates T cell response, B cell differentiation and immunoglobulin production. Endothelial cells can produce large amounts of IL-6. SNP at position -174 (G/C) in the IL-6 promoter region was found to be associated with a series of complex diseases. In this study we analyzed whether IL-6 -174 G/C polymorphism has any effect on IL-6 production of in vitro cultured HUVECs. Thirty-three fresh umbilical cords were recruited from healthy pregnancies. The endothelial cells isolated from human umbilical cords were genotyped for IL-6 -174 SNP. C allele frequency was 0.379. The IL-6 production of each primary HUVEC line was measured after IL-1beta or LPS treatment by ELISA. Serial dilutions of the stimulating agents were applied and maximum amount of produced IL-6 (R(max)) and stimulator concentrations at half maximal IL-6 response (MR(50)) were calculated for each of the cell lines. IL-6 production was not associated with IL-6 -174 SNP genotypes or with presence of C allele. Our results showed that IL-6 production of HUVEC after proinflammatory stimulation was not influenced by IL-6 -174 SNP. Further functional studies are required to compare differences and similarities in IL-6 -174 SNP dependent expression of IL-6 among various cell types. PMID- 17869128 TI - Application of laser induced electron impact ionization to the deposition chemistry in the hot-wire chemical vapor deposition process with SiH4-NH3 gas mixtures. AB - The application of a laser-induced electron impact (LIEI) ionization source in studying the gas-phase chemistry of the SiH(4)/NH(3) hot-wire chemical vapor deposition (HWCVD) system has been investigated. The LIEI source is achieved by directing an unfocused laser beam containing both 118 nm (10.5 eV) vacuum ultraviolet (VUV) and 355 nm UV radiations to the repeller plate in a time-of flight mass spectrometer. Comparison of the LIEI source with the conventional 118 nm VUV single-photon ionization (SPI) method has demonstrated that the intensities of the chemical species with ionization potentials (IP) above 10.5 eV, e.g., H(2), N(2) and He, have been significantly enhanced with the incorporation of the LIEI source. It is found that the SPI source due to the 118 nm VUV light coexists in the LIEI source. This allows simultaneous observations of parent ions with enhanced intensity from VUV SPI and their "fingerprint" fragmentation ions from LIEI. It is, therefore, an effective tool to diagnose the gas-phase chemical species involved with both NH(3) and SiH(4) in the HWCVD reactor. In using the LIEI source to SiH(4), NH(3) and their mixtures, it has been shown that the NH(3) decomposition is suppressed with the addition of SiH(4) molecules. Examination of the NH(3) decomposition percentage and the time to reach the N(2) and H(2) steady-state intensities for various NH(3)/SiH(4) mixtures suggests that the extent of the suppression is enhanced with more SiH(4) content in the mixture. With increasing filament temperatures, the negative effect of SiH(4) becomes less important. PMID- 17869130 TI - Structural models of the supramolecular organization of AQP0 and connexons in junctional microdomains. AB - Membrane proteins perform many essential cellular functions. Over the last years, substantial advances have been made in our understanding of the structure and function of isolated membrane proteins. However, like soluble proteins, many membrane proteins assemble into supramolecular complexes that perform specific functions in specialized membrane domains. Since supramolecular complexes of membrane proteins are difficult to study by conventional approaches, little is known about their composition, organization and assembly. The high signal-to noise ratio of the images that can be obtained with an atomic force microscope (AFM) makes this instrument a powerful tool to image membrane protein complexes within native membranes. Recently, we have reported high-resolution topographs of junctional microdomains in native eye lens membranes containing two-dimensional (2D) arrays of aquaporin-0 (AQP0) surrounded by connexons. While both proteins are involved in cell adhesion, AQP0 is a specific water channel whereas connexons form cell-cell communication channels with broad substrate specificity. Here, we have performed a detailed analysis of the supramolecular organization of AQP0 tetramers and connexon hexamers in junctional microdomains in the native lens membrane. We present first structural models of these junctional microdomains, which we generated by docking atomic models of AQP0 and connexons into the AFM topographs. The AQP0 2D arrays in the native membrane show the same molecular packing of tetramers seen in highly ordered double-layered 2D crystals obtained through reconstitution of purified AQP0. In contrast, the connexons that surround the AQP0 arrays are only loosely packed. Based on our AFM observations, we propose a mechanism that may explain the supramolecular organization of AQP0 and connexons in junctional domains in native lens membranes. PMID- 17869129 TI - Fragmentation of protonated dipeptides containing arginine. Effect of activation method. AB - The fragmentation reactions of the protonated dipeptides Gly-Arg and Arg-Gly have been studied using collision-induced dissociation (CID) in a quadrupole ion trap, by in-source CID in a single-quadrupole mass spectrometer and by CID in the quadrupole cell of a QqTOF mass spectrometer. In agreement with earlier quadrupole ion trap studies (Farrugia, J. M.; O'Hair, R. A. J., Int. J. Mass Spectrom., 2003, 222, 229), the CID mass spectra obtained with the ion trap for the MH(+) ions and major fragment ions are very similar for the two isomers indicating rearrangement to a common structure before fragmentation. In contrast, in-source CID of the MH(+) ions and QqTOF CID of the MH(+), [MH - NH(3)](+) and [MH <23 HN = C(NH(2))(2)](+) ions provide distinctly different spectra for the isomeric dipeptides, indicating that rearrangement to a common structure has not occurred to a significant extent under these conditions even near the threshold for fragmentation in the QqTOF instrument. Clearly, under normal operating conditions significantly different fragmentation behavior is observed in the ion trap and beam-type experiments. This different behavior probably can be attributed to the shorter observation times and concomitant higher excitation energies in the in-source and QqTOF experiments compared to the long observation times and lower excitation energies relevant to the ion trap experiments. Based largely on elemental compositions derived from accurate mass measurements in QqTOF studies fragmentation schemes are proposed for the MH(+), [MH - NH(3)](+), and [MH - (HN = C(NH(2))(2))](+) ions. PMID- 17869131 TI - Phylogenetic relationships within an endemic group of Malagasy 'assassin spiders' (Araneae, Archaeidae): ancestral character reconstruction, convergent evolution and biogeography. AB - The phylogenetic relationships in an endemic group of Malagasy 'assassin spiders' (Araneae, Archaeidae: Eriauchenius) called the gracilicollis group, are inferred from mitochondrial 12S, 16S and COI DNA sequence data. Archaeid spiders of Madagascar have evolved varying degrees of elongation in the cephalic area. These molecular data support the monophyly of the gracilicollis group. The evolution of the cephalic area is examined by performing an ancestral character reconstruction on this character, which reveals that the cephalic area is elongating independently. The biogeography of the gracilicollis group reveals an east-west split of the clade on Madagascar. PMID- 17869132 TI - Life-long environmental enrichment differentially affects the mnemonic response to estrogen in young, middle-aged, and aged female mice. AB - The present study was designed to examine whether life-long exposure to standard or enriched housing affects the ability of estrogen to improve spatial and object memory throughout the lifespan. Three-week-old female mice were maintained in standard or enriched housing up to and through ovariectomy and behavioral testing at 5, 17, or 22 months of age. Spatial memory was tested in the Morris water maze and object memory was tested using an object recognition task. Immediately after training each day, mice were injected intraperitoneally with vehicle or 0.2 mg/kg 17beta-estradiol. Among young females, object recognition was enhanced by estradiol alone, an effect that was reduced by enrichment. In contrast, spatial water maze performance was impaired by estradiol alone, but improved by the combination of both estradiol and enrichment. At middle-age, object recognition was enhanced by estradiol or enrichment alone, and the combination of both treatments. Spatial memory in the water maze was also improved by both treatments at middle-age, but the beneficial effects of estradiol were limited to standard housed females. Finally, whereas enrichment in aged females significantly enhanced performance in both tasks, estradiol had no effect at this age in either task. In total, the data indicate that life-long enrichment can significantly alter the extent to which estradiol affects memory in mice throughout the lifespan. Importantly, the interaction between these treatments is highly dependent on age and type of memory tested. PMID- 17869134 TI - Antigen crosspresentation by human plasmacytoid dendritic cells. AB - Crosspresentation is a specialized function of myeloid dendritic cells (mDCs), allowing them to induce CD8+ T cell responses against exogenous antigens that are not directly produced in their cytotosol. Human plasmacytoid DCs (pDCs) are not considered so far as able to perform crosspresentation. We showed here that purified human pDCs crosspresented vaccinal lipopeptides and HIV-1 antigens from apoptotic cells to specific CD8+ T lymphocytes. Apoptotic debris were internalized by phagocytosis and the lipopeptide LPPol reached nonacidic endosomes. This crosspresentation was amplified upon influenza virus infection. Importantly, the efficiency of crosspresentation by pDCs was comparable to that of mDCs. This property of human pDCs needs to be taken into account to understand the pathogenesis of infectious, allergic, or autimmune diseases and to help achieve desired responses during vaccination by targeting specifically either type of DCs. PMID- 17869133 TI - Nonself-antigens are the cognate specificities of Foxp3+ regulatory T cells. AB - The majority of regulatory Foxp3+CD4+ T cells naturally arises in the thymus. It has been proposed that T cell receptors (TCRs) on these cells recognize self-MHC class II-peptide complexes with high or higher affinity and that their specificities mirror specificities of autoreactive T cells. Here, we analyzed hundreds of TCRs derived from regulatory or nonregulatory T cells and found little evidence that the former population preferably recognizes self-antigens as agonists. Instead, these cells recognized foreign MHC-peptide complexes as often as nonregulatory T cells. Our results show that high-affinity, autoreactive TCRs are rare on all CD4+ T cells and suggest that selecting self-peptide is different from the peptide that activates the same regulatory T cells in the periphery. PMID- 17869135 TI - Surrogate-light-chain silencing is not critical for the limitation of pre-B cell expansion but is for the termination of constitutive signaling. AB - The pre-B cell receptor (pre-BCR), composed of immunoglobulin mu heavy chain and the surrogate light chain (SLC) proteins lambda5 and Vpreb, signals for proliferation and maturation of developing pre-B cells. It has been assumed that pre-B cells stop cycling by the pre-BCR-mediated downregulation of SLC transcription. We generated transgenic mice expressing SLC throughout B cell development and, remarkably, found that enforced SLC expression had no effect on pre-B cell proliferation or differentiation. However, in the presence of conventional immunoglobulin light chains, SLC components had the capacity to induce constitutive BCR internalization, secondary immunoglobulin light-chain rearrangement, and a severe developmental arrest of immature B cells, dependent on the adaptor protein Slp65. Residual B cells in the spleen showed increased expression of surface CD5, which is a negative regulator of BCR signaling, and differentiated spontaneously into IgM+ plasma cells. Thus, the silencing of SLC genes is not essential for the limitation of pre-B cell proliferation, but is required for the prevention of constitutive activation of B cells. PMID- 17869137 TI - Salivary detection of periodontopathic bacteria in periodontally healthy children. AB - BACKGROUND: Salivary occurrence of periodontopathic bacteria is of interest especially in children as a risk indicator for the transmission, development and control of periodontal disease. We assessed the prevalence of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Prevotella intermedia, Prevotella nigrescens and Treponema denticola as microbial complexes in the saliva of children with mixed dentition and healthy gingiva. MATERIALS AND METHODS: Paraffin-stimulated saliva samples were collected from 41 children (22 boys and 19 girls), aged 6-13 years old. Gingival health was determined during the initial screening exam. The test bacteria were identified using a 16S rRNA based PCR analysis. RESULTS: P. nigrescens was the most frequent species (80%), followed by T. denticola (32%), A. actinomycetemcomitans (24%) and P. gingivalis (12%). P. intermedia and T. forsythia were not detected. P. nigrescens was also common species in combinations. Paired and triple bacterial combinations were found in 24% and 20% of all children, respectively. There was no positive association between bacterial combinations in colonization and subject's gender (P>0.05, Fisher exact test). CONCLUSION: The salivary presence of P. nigrescens, T. denticola, A. actinomycetemcomitans and P. gingivalis but not P. intermedia and T. forsythia can occur in childhood without clinical signs of gingival disease. Thus, the possible risk of bacterial transmissions through saliva and, the need to screen for periodontal pathogens should be considered before mixed dentition. PMID- 17869136 TI - A role for the IkappaB family member Bcl-3 in the control of central immunologic tolerance. AB - Bcl-3 is a member of the family of IkappaB inhibitors. Unlike the classical, cytoplasmic IkappaBs, Bcl-3 does not inhibit RelA- or c-Rel-containing NF-kappaB transcription factor dimers. Instead, Bcl-3 can enter the nucleus and modulate NF kappaB activity, although the underlying mechanism and physiologic function remain largely unknown. Here we identified Bcl-3 as a regulator of immunologic tolerance to self. In parallel with NF-kappaB2, Bcl-3 functions within stroma to generate medullary thymic epithelial cells, which are essential for negative selection of autoreactive T cells. Loss of both NF-kappaB2 and Bcl-3, but not either one alone, led to a profound breakdown in central tolerance resulting in rapid and fatal multiorgan inflammation. These data reveal extensive utilization of the NF-kappaB system to promote central tolerance in the thymus, in apparent contrast with the well-known roles of NF-kappaB to promote inflammation and autoimmunity in the periphery. PMID- 17869138 TI - Comparison of risk-scoring methods in predicting the immediate outcome after elective open abdominal aortic aneurysm surgery. AB - BACKGROUND & OBJECTIVES: The aim of this study was to apply three simple risk - scoring systems to prospectively collected data on all elective open Abdominal Aortic Aneurysm (AAA) operations in the Cambridge Academic Vascular Unit over a 6 - year period (January 1998 to January 2004), to compare their predictive values and to evaluate their validity with respect to prediction of mortality and post operative complications. METHODS: 204 patients underwent elective open infra renal AAA repair. Data were prospectively collected and risk assessment scores were calculated for mortality and morbidity according to the Glasgow Aneurysm Score (GAS), VBHOM (Vascular Biochemistry and Haematology Outcome Models) and Estimation of Physiologic Ability and Surgical Stress (E-PASS). RESULTS: The mortality rate was 6.3% (13/204) and 59% (121/204) experienced a post-operative complication (30-day outcome). For GAS, VBHOM and E-PASS the receiver operating characteristics (ROC) curve analysis for prediction of in-hospital mortality showed area under the curve (AUC) of 0.84 (95% confidence interval [CI], 0.76 to 0.92; p<0.0001), 0.82 (95% CI, 0.68 to 0.95; p=0.0001) and 0.92 (95% CI, 0.87 to 0.97; p<0.0001) respectively. There were also significant correlations between post-operative complications and length of hospital stay and each of the three scores, but the correlation was substantially higher in the case of E-PASS. CONCLUSIONS: All three scoring systems accurately predicted the risk of mortality and morbidity in patients undergoing elective open AAA repair. Among these, E PASS seemed to be the most accurate predictor in this patient population. PMID- 17869139 TI - Risk factors for strap-related lesions in working donkeys at the World Heritage Site of Petra in Jordan. AB - A risk analysis was undertaken in an attempt to improve improvised rump straps on donkeys carrying tourists at the World Heritage Site at Petra, Jordan. Tail-base lesions were identified in 63 of the 86 donkeys. Observations and questionnaires were used to collect data relating to the straps, donkey health and human attitudes. The worse lesions were associated with padded rather than unpadded straps, if tightly fitted. Padding could be a cause of, or a response to lesions, but results suggest that it did not effectively aid healing. Significantly worse lesions occurred with unclean than with clean straps and, contrary to many recommendations, cotton straps were associated with worse lesions than were synthetic straps. Since this was an exploratory study, findings should be considered to generate (not to test) hypotheses and any resulting interventions will require monitoring. Further possible risks are discussed, referring to medical and veterinary literature and applied expertise in working equines. PMID- 17869140 TI - Magnetic stimulation of peripheral nerves in dogs: a pilot study. AB - A model for magnetic stimulation of the radial and sciatic nerves in dogs was evaluated. Onset-latencies and peak-to-peak amplitudes of magnetic and electrical stimulation of the sciatic nerve were compared, and the effect of the direction of the current in the magnetic coil on onset-latencies and peak-to-peak amplitude of the magnetic motor evoked potential was studied in both nerves. The results demonstrate that magnetic stimulation is a feasible method for stimulating the radial and sciatic nerves in dogs. No significant differences were observed in onset-latencies and peak-to-peak amplitudes during magnetic and electrical stimulation, indicating conformity between the techniques. Orthodromic or antidromic magnetic nerve stimulation resulted in no significant differences. This pilot study demonstrates the potential of magnetic stimulation of nerves in dogs. PMID- 17869141 TI - Risk factors associated with the occurrence of frontoethmoidal encephalomeningocele. AB - OBJECTIVES: To determine factors associated with the occurrence of frontoethmoidal encephalomeningocele (FEEM), a congenital defect with unique geographical distribution. METHODS: The subjects of this study were 160 unrelated cases of FEEM. Subjects were recruited between 1999 and 2006 from 15 medical centers throughout Thailand. Data obtained from FEEM cases were analyzed and compared with data from 349 cases of oral clefts studied in the same centers and during the same time and those from the general population (GP) taken in 2003. RESULTS: About 52% of FEEM cases had brain anomalies which were not different among types of FEEM. We found familial aggregation reflected by an increased risk to siblings. All of the FEEM cases were of Thai nationality and came from low socioeconomic status. Seven FEEM cases had amniotic rupture sequences. Compared with oral clefts, advanced maternal age (OR: 1.08, 95% CI: 1.02-1.15) was found to be associated with FEEM. In addition, the interpregnancy interval between the FEEM cases and their previous siblings was significantly longer than that of the oral cleft patients and unaffected sibs (OR: 1.17, 95% CI: 1.06-1.28). CONCLUSIONS: Low socioeconomic status, advanced maternal age, and a long interpregnancy interval may lead to an unfavorable intrauterine environment which, with a certain genetic background such as Thai ethnicity, could contribute to the occurrence of FEEM. PMID- 17869142 TI - Differential diagnosis of cerebellar atrophy in childhood. AB - Starting from the imaging appearance of cerebellar atrophy (CA) we provide checklists for various groups of CA: hereditary CA, postnatally acquired CA, and unilateral CA. We also include a list of disorders with ataxia as symptom, but no evidence of CA on imaging. These checklists may be helpful in the evaluation of differential diagnosis and planning of additional investigations. However, the complete constellation of clinical (including history and neurological examination), imaging, and other information have to be considered. On the basis of a single study distinction between prenatal onset atrophy, postnatal onset atrophy, and cerebellar hypoplasia is not always possible. Apart from rare exceptions, neuroimaging findings of CA are nonspecific. A pattern-recognition approach is suggested, considering isolated (pure) CA, CA and hypomyelination, CA and progressive white matter abnormalities, CA and basal ganglia involvement, and cerebellar cortex hyperintensity. PMID- 17869143 TI - Procedural pain--time for its recognition and treatment! PMID- 17869144 TI - Dose- and time-dependent estradiol modulation of morphine antinociception in adult female rats. AB - To clarify the activational role of ovarian hormones on pain and analgesia, the present study determined whether estradiol (E2) modulation of nociception and morphine antinociception in adult female rats depends on (1) the dose of E2 and (2) the interval between E2 treatment and nociceptive testing. Female rats were ovariectomized (OvX) and either oil vehicle (0), or E2 (0.25, 2.5 or 25 microg/0.1 ml vehicle) was injected s.c. two consecutive days of every four days for five cycles before testing. Either 4, 24, 48 or 96 h after the last injection, nociception was evaluated on the 50 degrees C hotplate and warm water tail withdrawal tests before and after escalating doses of s.c. morphine. Lordosis behavior and uterine weight were assessed in other rats at the same E2 doses and time points. E2 significantly lengthened latency to respond on the hotplate test at 24 h after the last injection, but had no significant effect on tail withdrawal latencies. The lower doses of E2 significantly increased morphine antinociceptive potency at 4-24 h on one or both tests, but the intermediate E2 dose significantly decreased morphine potency at 48 h on the hotplate test. Thus, E2 modulation of morphine antinociception in the adult female rat is bidirectional, and occurs at E2 doses producing cyclic changes in sexual behavior, uterine weight and vaginal cytology that are similar to those observed in gonadally intact, cycling females. PMID- 17869145 TI - More on pain semantics. PMID- 17869146 TI - Morphine-6-glucuronide (M6G) for postoperative pain relief. AB - Morphine-6-glucuronide (M6G) is morphine's active metabolite acting at the mu opioid receptor. Recent experimental human studies and 5 of 6 randomized clinical trials indicate that M6G causes adequate and long lasting pain relief comparable to morphine. There are various observations that M6G is associated with a reduction in the severity of side effects normally associated with opioid use, such as reduced postoperative nausea and vomiting (PONV) and reduced respiratory depression. The present drug profile provides a review of the pharmacological properties of M6G, the clinical evidence relating to its efficacy and safety, and discusses its future role in the treatment of postoperative pain. PMID- 17869147 TI - Detection of microscopic anisotropy in gray matter and in a novel tissue phantom using double Pulsed Gradient Spin Echo MR. AB - A double Pulsed Gradient Spin Echo (d-PGSE) MR experiment was used to measure and assess the degree of local diffusion anisotropy in brain gray matter, and in a novel "gray matter" phantom that consists of randomly oriented tubes filled with water. In both samples, isotropic diffusion was observed at a macroscopic scale while anisotropic diffusion was observed at a microscopic scale, however, the nature of the resulting echo attenuation profiles were qualitatively different. Gray matter, which contains multiple cell types and fibers, exhibits a more complicated echo attenuation profile than the phantom. Since microscopic anisotropy was observed in both samples in the low q regime comparable to that achievable in clinical scanner, it may offer a new potential contrast mechanism for characterizing gray matter microstructure in medical and biological applications. PMID- 17869148 TI - Mechanism of decongestant activity of alpha 2-adrenoceptor agonists. AB - The vascular bed in nasal mucosa of different species, including human, is highly vascularized and an extensive sinusoidal network of large capacitance vessels is present deep within the submucosa. When this network of venous sinusoids is engorged with blood, the swollen mucosa reduces the size of the airway lumen and congestion ensues. Nasal vasculature tone is strongly influenced by the sympathetic nervous system and the only drugs approved specifically to relieve vascular nasal obstruction are alpha-adrenoceptor sympathomimetic agents. Due to their vasoconstrictor action, the sympathomimetic decongestants oppose vasodilation, reducing nasal airway resistance and thus facilitating nose breathing. However, standard decongestants that are non-selective alpha adrenoceptor agonists are associated with the potential for side-effect liabilities including hypertension, stroke, insomnia and nervousness. We propose than a selective alpha 2-adrenoceptor agonist, by acting preferentially on nasal venous capacitance vessels, will elicit decongestion with a reduced side-effect liability. In the present study, we evaluated the effects of the selective alpha 2-adrenoceptor agonist BHT-920 in a real-time tissue contractility assay using isolated pig nasal explants and in an in vivo cat model of congestion. The vasoconstrictor and decongestant effects of BHT-920 were compared to the non selective alpha-adrenoceptor agonist epinephrine and the standard decongestant oxymetazoline. Our results showed that the alpha 2-adrenoceptor agonist BHT-920 preferentially contracts venous sinusoids confirming previous observations [Corboz MR, Varty LM, Rivelli MA, Mutter JC, Mingo G, McLeod R, et al. Effects of an alpha 2-adrenoceptor agonist in nasal mucosa. Arch Physiol Biochem 2003;11: 335-6, Corboz MR, Rivelli MA, Varty LM, Mutter J, Cartwright M, Rizzo CA, et al. Pharmacological characterization of postjunctional alpha-adrenoceptor in human nasal mucosa. Am J Rhinol 2005;19: 495-502] and displays decongestion without affecting blood pressure. Therefore, an alpha 2-adrenoceptor agonist, by causing constriction in the capacitance vessels of nasal mucosa, can produce nasal decongestion without the effects on blood pressure observed with the standard selective alpha 1-adrenoceptor and non-selective alpha-adrenoceptor sympathomimetic decongestants. PMID- 17869149 TI - Pulmonary versus systemic delivery of levofloxacin. The isolated lung of the rat as experimental approach for assessing pulmonary inhalation. AB - The present work was aimed to compare levofloxacin pulmonary disposition after systemic or inhalatory delivery and to evaluate the influence of respiratory pattern on lung distribution. An experimental model of the isolated lung of the rat was used. Twenty-four Wistar rats were distributed in four groups receiving levofloxacin under different experimental conditions including systemic or pulmonary delivery and higher or lower respiratory frequency with lower or higher tidal volume, respectively. Levofloxacin (500 microg) was administered as a bolus injection or by inhalation. Lung tissue samples as well as efferent and broncoalveolar fluid were collected. Quantification of levofloxacin levels in all samples was performed by a high-performance liquid chromatography (HPLC) technique. Pulmonary distribution coefficient of levofloxacin after systemic delivery showed mean values of 1.19+/-0.13 and 3.34+/-0.61 ml/g for each respiratory pattern assayed. The partition coefficients estimated from simultaneous drug level in lung tissue and efferent fluid (EF) are in agreement with the above values. Comparison of systemic and pulmonary administration reveals statistical significant differences between partition coefficients showing much higher values for the latter route (8.01+/-5.53 versus 2.86+/-1.35). In conclusion, inhalation compared to systemic administration improves levofloxacin access to the lung tissue; the experimental approach used here to assess the pulmonary drug disposition may be a useful model for biopharmaceutical studies of inhaled therapeutics. PMID- 17869150 TI - Changes in cardiac output during swimming and aquatic hypoxia in the air breathing Pacific tarpon. AB - Pacific tarpon (Megalops cyprinoides) use a modified gas bladder as an air breathing organ (ABO). We examined changes in cardiac output (V(b)) associated with increases in air-breathing that accompany exercise and aquatic hypoxia. Juvenile (0.49 kg) and adult (1.21 kg) tarpon were allowed to recover in a swim flume at 27 degrees C after being instrumented with a Doppler flow probe around the ventral aorta to monitor V(b) and with a fibre-optic oxygen sensor in the ABO to monitor air-breathing frequency. Under normoxic conditions and in both juveniles and adults, routine air-breathing frequency was 0.03 breaths min(-1) and V(b) was about 15 mL min(-1) kg(-1). Normoxic exercise (swimming at about 1.1 body lengths s(-1)) increased air-breathing frequency by 8-fold in both groups (reaching 0.23 breaths min(-1)) and increased V(b) by 3-fold for juveniles and 2 fold for adults. Hypoxic exposure (2 kPa O2) at rest increased air-breathing frequency 19-fold (to around 0.53 breaths min(-1)) in both groups, and while V(b) again increased 3-fold in resting juvenile fish, V(b) was unchanged in resting adult fish. Exercise in hypoxia increased air-breathing frequency 35-fold (to 0.95 breaths min(-1)) in comparison with resting normoxic fish. While juvenile fish increased V(b) nearly 2-fold with exercise in hypoxia, adult fish maintained the same V(b) irrespective of exercise state and became agitated in comparison. These results imply that air-breathing during exercise and hypoxia can benefit oxygen delivery, but to differing degrees in juvenile and adult tarpon. We discuss this difference in the context of myocardial oxygen supply. PMID- 17869151 TI - Squash-preparation cytology from nasopharyngeal masses in the cat: cytological results and histological correlations in 30 cases. AB - Upper airway obstruction in cats can be a life-threatening condition. Early recognition of clinical signs and an appropriate diagnostic approach increases the possibility of appropriate therapeutic choices. The purpose of this study was to assess the efficacy and diagnostic value of squash-preparation cytology in providing an accurate diagnosis of masses growing in the nasopharynx of cats. Cytological specimens prepared by a squash technique from nasopharyngeal masses in 30 cats were collected under direct endoscopic guidance and classified into four groups: benign inflammatory/hyperplastic mass, lymphoma, carcinoma and sarcoma. The cytopathological diagnosis was compared with the final histopathological diagnosis and indices of diagnostic test accuracy were calculated. The results showed good agreement between the cytological and histological diagnosis with a sensitivity of 0.94, a specificity of 0.81, a positive likelihood ratio of 0.9, a negative likelihood ratio of 0.9 and an overall accuracy of 0.9. Squash-preparation cytology is considered an accurate diagnostic tool for distinguishing benign from malignant nasopharyngeal masses in cats. For differentiation of lymphoma and lymphoid reactions histopathological confirmation is recommended. PMID- 17869152 TI - [Left extraperitoneal laparoscopic para-aortic lymphadenectomy: morbidity and learning curve of the technique]. AB - OBJECTIVE: Description of the morbidity and the learning curve of the left extraperitoneal laparoscopic paraaortic lymphadenectomy in patients with gynecologic cancers. PATIENTS AND METHODS: Retrospective study of patients treated with the left extraperitoneal laparoscopic paraaortic lymphadenectomy between August 1999 and January 2005. Duration of surgery, per and post-operative complications, duration of the hospital stay, number of retrieved nodes, and pathologic results were studied. A comparative analysis of the results was performed between trained and training surgeons. RESULTS: Eighty-one patients were planned for the left extraperitoneal laparoscopic paraaortic lymphadenectomy. The major indication (90% of cases) was advanced cervical carcinomas (stage IB2 and more). The median number of retrieved nodes was 14, with a mean operative time of 109 minutes. The median hospital stay was 3 days. Two major complications related to the surgical technique were observed: a laceration of the inferior vena cava and an acute abdominal syndrome. Seven lymphocysts (8.6%) were observed (with associated symptoms in 2 cases). Trained surgeons to the technique displayed higher success rate of this surgical technique and higher number of retrieved lymph nodes. DISCUSSION AND CONCLUSIONS: The left extraperitoneal laparoscopic paraaortic lymphadenectomy allows the accurate staging and management of patients with gynecologic cancers and mainly women affected by advanced cervical carcinoma. The surgical technique is safe and reproducible when performed by trained surgeons. PMID- 17869153 TI - [Posterior IVS: feasibility and preliminary results in a continuous series of 108 cases]. AB - OBJECTIVE: We present a continuous series of 108 patients operated for genital prolapse by vaginal route using the Posterior Intravaginal Slingplasty (PIVS) technique (IVS 02 Tyco Healthcare, polypropylene multifilament band), associated to prosthetic repair of cystocele and/or rectocele if present by interposition of a mesh (Surgipro Mesh Tyco Healthcare). PATIENTS AND METHODS: Inclusion criteria were C and/or D point superior to -1 cm. The main criterion is the assessment of feasibility, morbidity and anatomical results obtained for the treatment of level 1 genital prolapse with an average follow-up of 19 months. The secondary criterion is to assess the same elements for the treatment of associated cystocele and rectocele. RESULTS: Seventy-three patients presented with a cystocele (Ba>-1 cm) and eighty-seven with a rectocele (Bp>-1 cm). Nineteen patients had a hysterectomy, twenty had amputation of the cervix and forty-nine were treated for stress urinary incontinence by anterior IVS. Perioperative complications consisted of seven bladder injuries, one injury to the lower rectum during dissection. Postoperative complications were: a loss more than 2 g haemoglobin for seven patients, two haematomas in the cave of Retzius, one haematoma of the pararectal fossa with secondary superinfection requiring mesh removal. Three erosions occurred: two in front of the vesicovaginal prosthesis and one in front of the recto-vaginal prosthesis. The latter became secondarily super infected and had to be removed. With regard to the anatomical result, one failure was noted for the Posterior IVS excluding the two patients in whom the prosthetic material had to be removed. For the anterior compartment, eight failures occurred. From a functional perspective, we noted one case of dyspareunia due to fibrous retraction and seven patients complained of de novo stress urinary incontinence and eight of moderate voiding obstruction. DISCUSSION AND CONCLUSIONS: The technical feasibility is excellent. Feasibility of level 2 repair, anterior or posterior, but results on cystocele are insufficient in case of lateral defect. PMID- 17869154 TI - [Who is it necessary to vaccine against whooping-cough?]. AB - Whooping-cough is one of the rare diseases for which vaccine prevention has been available for many years. However, in spite of good vaccine coverage in the infant, the pertussis infection remains a frequent disease in the teenagers and adults partially immunized. The missing diagnosis of the infection, added to its often clinical banal expression, contributes to support the circulation of Bordetella pertussis and explains the contamination of the young infants in whom the disease remains a true danger as the few declared deaths show it every year. Control of the disease must go through reinforcement of vaccination as a practitioner of booster vaccine in preadolescents, teenagers and adults. Instituted since 1998 in the French vaccine calendar, the 2nd booster in preadolescence between 11-13 years olds or 5th dose of vaccine is not enough carried out and must be encouraged like the installation of another additional vaccine dose for adults and certain professional categories. The protection of infants too young to have received the 3 doses goes through the vaccination of their entourage, family and socio-professional alike. The new recommendations thus preach to begin vaccination in children from the age of 2 months, a reinforcement of the vaccine boosters in preadolescents, in adults likely to become parents and in the medical and paramedical personnel in contact with very young infants. PMID- 17869155 TI - [Pelviperineoscopy. Preliminary study and feasibility of use of cadavers]. PMID- 17869156 TI - [Obstetrical and neonatal consequences of gestational diabetes in the south of Reunion Island]. PMID- 17869157 TI - [Is cerebral palsy preventable?]. PMID- 17869158 TI - Shock-wave model of acoustic cavitation. AB - Shock-wave model of liquid cavitation due to an acoustic wave was developed, showing how the primary energy of an acoustic radiator is absorbed in the cavitation region owing to the formation of spherical shock-waves inside each gas bubble. The model is based on the concept of a hypothetical spatial wave moving through the cavitation region. It permits using the classical system of Rankine Hugoniot equations to calculate the total energy absorbed in the cavitation region. Additionally, the model makes it possible to explain some newly discovered properties of acoustic cavitation that occur at extremely high oscillatory velocities of the radiators, at which the mode of bubble oscillation changes and the bubble behavior approaches that of an empty Rayleigh cavity. Experimental verification of the proposed model was conducted using an acoustic calorimeter with a set of barbell horns. The maximum amplitude of the oscillatory velocity of the horns' radiating surfaces was 17 m/s. Static pressure in the calorimeter was varied in the range from 1 to 5 bars. The experimental data and the results of the calculations according to the proposed model were in good agreement. Simple algebraic expressions that follow from the model can be used for engineering calculations of the energy parameters of the ultrasonic radiators used in sonochemical reactors. PMID- 17869159 TI - Smart Vest: wearable multi-parameter remote physiological monitoring system. AB - The wearable physiological monitoring system is a washable shirt, which uses an array of sensors connected to a central processing unit with firmware for continuously monitoring physiological signals. The data collected can be correlated to produce an overall picture of the wearer's health. In this paper, we discuss the wearable physiological monitoring system called 'Smart Vest'. The Smart Vest consists of a comfortable to wear vest with sensors integrated for monitoring physiological parameters, wearable data acquisition and processing hardware and remote monitoring station. The wearable data acquisition system is designed using microcontroller and interfaced with wireless communication and global positioning system (GPS) modules. The physiological signals monitored are electrocardiogram (ECG), photoplethysmogram (PPG), body temperature, blood pressure, galvanic skin response (GSR) and heart rate. The acquired physiological signals are sampled at 250samples/s, digitized at 12-bit resolution and transmitted wireless to a remote physiological monitoring station along with the geo-location of the wearer. The paper describes a prototype Smart Vest system used for remote monitoring of physiological parameters and the clinical validation of the data are also presented. PMID- 17869160 TI - In vivo measurements of the elastic mechanical properties of human skin by indentation tests. AB - Knowledge about the human skin mechanical properties is essential in several domains, particularly for dermatology, cosmetic or to detect some cutaneous pathology. This study proposes a new method to determine the human skin mechanical properties in vivo using the indentation test. Usually, the skin mechanical parameters obtained with this method are influenced by the mechanical properties of the subcutaneous layers, like muscles. In this study, different mechanical models were used to evaluate the effect of the subcutaneous layers on the measurements and to extract the skin elastic properties from the global mechanical response. The obtained results demonstrate that it is necessary to take into account the effect of the subcutaneous layers to correctly estimate the skin Young's modulus. Moreover, the results illustrate that the variation of the measured Young's modulus at low penetration depth cannot be correctly described with usual one-layer mechanical models. Thus a two-layer elastic model was proposed, which highly improved the measurement of the skin mechanical properties. PMID- 17869161 TI - Methylglyoxal causes strong weakening of detoxifying capacity and apoptotic cell death in rat hippocampal neurons. AB - The hippocampus is known to play a crucial role in learning and memory. Recent data from literature show that cognitive problems, common to aged or diabetic patients, may be related to accumulation of toxic alpha-oxoaldehydes such as methylglyoxal. Thus, it is possible that methylglyoxal could be, at least in part, responsible for the impairment of cognitive functions, and the knowledge of the mechanisms through which this compound elicits neuronal toxicity could be useful for the development of possible therapeutic strategies. We previously reported a high susceptibility of hippocampal neurons to methylglyoxal, through an oxidation-dependent mechanism. In the present study, we extend our investigation on the molecular mechanisms which underlie methylglyoxal toxicity, focusing on possible effects on expression and activity of glyoxalases, its main detoxifying enzymes, and glutathione peroxidase, as well as on the levels of reduced glutathione. We also investigate methylglyoxal-induced modulation of brain derived neurotrophic factor and proinflammatory cytokines. Our results show that methylglyoxal causes a dramatic depletion of reduced glutathione and a significant inhibition of both glyoxalase and glutathione peroxidase activities. Furthermore, methylglyoxal treatment seems to affect the expression of inflammatory cytokines and survival factors. In conclusion, our findings suggest that methylglyoxal-induced neurotoxicity occurs through the impairment of detoxification pathway and depletion of reduced glutathione. This, in turn, triggers widespread apoptotic cell death, occurring through the convergence of both mitochondrial and Fas-receptor pathways. PMID- 17869162 TI - TNF-alpha-induced self expression in human lung endothelial cells is inhibited by native and oxidized alpha1-antitrypsin. AB - Endothelial cells are among the main physiological targets of the pro inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). In endothelial cells TNF-alpha elicits a broad spectrum of biological effects including differentiation, proliferation and apoptosis. alpha1-antitrypsin (AAT), an endogenous inhibitor of serine proteases plays a vital role in protecting host tissue from proteolytic injury at sites of inflammation. Recently, it has been shown that AAT can be internalized by pulmonary endothelial cells, raising speculation that it may modulate endothelial cell function in addition to suppressing protease activity. Using Affymetrix microarray technology, real time PCR and ELISA methods we have investigated the effects of AAT on un-stimulated and TNF-alpha stimulated human primary lung microvascular endothelial cell gene expression and protein secretion. We find that AAT and TNF-alpha generally induced expression of distinct gene families with AAT exhibiting little activity in terms of inflammatory gene expression. Approximately 25% of genes up regulated by TNF-alpha were inhibited by co-administration of AAT including TNF-alpha induced self expression. Surprisingly, the effects of AAT on TNF-alpha-induced self expression was inhibited equally well by oxidized AAT, a modified form of AAT, which lacks serine protease inhibitor activity. Overall, the pattern of gene expression regulated by native and oxidized AAT was similar with neither inducing pro-inflammatory gene expression. These findings suggest that inhibitory effects of native and oxidized forms of AAT on TNF-alpha stimulated gene expression may play an important role in limiting the uncontrolled endothelial cell activation and vascular injury in inflammatory disease. PMID- 17869163 TI - Binding isotope effects: boon and bane. AB - Kinetic isotope effects are increasingly applied to investigate enzyme reactions and have been used to understand transition state structure, reaction mechanisms, quantum mechanical hydride ion tunneling and to design transition state analogue inhibitors. Binding isotope effects are an inherent part of most isotope effect measurements but are usually assumed to be negligible. More detailed studies have established surprisingly large binding isotope effects with lactate dehydrogenase, hexokinase, thymidine phosphorylase, and purine nucleoside phosphorylase. Binding reactants into catalytic sites immobilizes conformationally flexible groups, polarizes bonds, and distorts bond angle geometry, all of which generate binding isotope effects. Binding isotope effects are easily measured and provide high-resolution and detailed information on the atomic changes resulting from ligand-macromolecular interactions. Although binding isotope effects complicate kinetic isotope effect analysis, they also provide a powerful tool for finding atomic distortion in molecular interactions. PMID- 17869164 TI - Raman spectroscopy of the system iron(III)-sulfuric acid-water: an approach to Tinto River's (Spain) hydrogeochemistry. AB - Acid mine drainage is formed when pyrite (FeS(2)) is exposed and reacts with air and water to form sulfuric acid and dissolved iron. Tinto River (Huelva, Spain) is an example of this phenomenon. In this study, Raman spectroscopy has been used to investigate the speciation of the system iron(III)-sulfuric acid-water as an approach to Tinto River's aqueous solutions. The molalities of sulfuric acid (0.09 mol/kg) and iron(III) (0.01-1.5 mol/kg) were chosen to mimic the concentration of the species in Tinto River waters. Raman spectra of the solutions reveal a strong iron(III)-sulfate inner-sphere interaction through the nu(1) sulfate band at 981 cm(-1) and its shoulder at 1005 cm(-1). Iron(III) sulfate interaction may also be facilitated by hydrogen bonds and monitored in the Raman spectra through the symmetric stretching band of bisulfate at 1052 cm( 1) and a shoulder at 1040 cm(-1). Other bands in the low-frequency region of the Raman spectra are attributed to the hydrogen-bonded complexes formation as well. PMID- 17869165 TI - Application of Raman microscopy to the characterization of different verdigris variants obtained using recipes from old treatises. AB - Verdigris is an historical pigment of synthetic origin widely used in the artistic scope, from the antiquity to beginning of 19th century. It is a greenish or green-bluish colored product resulting from corrosion of pure copper and alloys caused by the action of different chemical reagents. The preparation recipes are numerous and appear in old texts, such as: treatises of art and texts of alchemy, as well as in books of secrets, natural history and those concerning medicines. A comparative study of these recipes shows significant differences depending on the initial components and the methodology applied in the synthesis of the pigment. Consequently, typical verdigris pigments very likely correspond to a variety of chemical compositions and, in addition, it might contain certain amounts of unknown by-products. To confirm such hypothesis, four different preparation recipes of verdigris have been carefully reproduced in our laboratory, and characterized by Raman microscopy. Our experiments allowed us to establish interesting differences among the studied samples. Some differences are mostly related to the ingredients used in the elaboration of the so-called raw verdigris. In other cases, the observed variations are consequence of the recrystallization treatment of the pigment. In general, all spectra reveal the existence of common component, namely, the copper(II) acetate (hydrated or anhydrous). However, other minority components have been detected in our samples, for instance, copper oxides, copper chlorides, and ammonic salts. In some cases, these compounds allow us to deduce the type of recipe used in the elaboration of the pigment. PMID- 17869166 TI - ESR, electrochemical and reactivity studies of antitrypanosomal palladium thiosemicarbazone complexes. AB - Cyclic voltammetry (CV) and electron spin resonance (ESR) techniques were used in the investigation of novel palladium complexes with bioactive thiosemicarbazones derived from 5-nitrofurane or 5-nitrofurylacroleine. Sixteen palladium complexes grouped in two series of the formula [PdCl(2)HL] or [PdL(2)] were studied. ESR spectra of the free radicals obtained by electrolytic reduction were characterized and analyzed. The ESR spectra showed two different hyperfine patterns. The stoichiometry of the complexes does not seem to affect significantly the hyperfine constants however we observed great differences between 5-nitrofurane and 5-nitrofurylacroleine derivatives. The scavenger properties of this family of compounds were lower than Trolox. PMID- 17869167 TI - Synthesis, spectroscopy, X-ray structure and redox behaviors of 4-(N-R salicylideneimine)-2,6-diphenylphenols. AB - A series of sterically hindered 4-(N-R-salicylaldimine)-2,6-diphenylphenols (X), where R=H (1), 3-CH3 (2), 5-CH3 (3), 3-OCH3 (4), 4-OCH3 (5), 5-OCH3 (6), 3-tBu (7), 5-tBu (8), 3,5-tBu2(9) and 5,6-benzo(10), were synthesized and their structure as well as redox behavior studied by analytical, spectroscopic [1H, (13C) NMR, IR, UV-vis and mass spectrometry] and cyclic voltammetric (CV) techniques. Single crystal X-ray diffraction studies of 7 evidenced its existence as non-planar enol-imine tautomer structure, in which the phenol ring of the molecule is twisted around C-N single bond by 21.5(2) degrees. The packing structure of 7 is stabilized by C-H...pi(Ph) and O...O and C...O intermolecular short contact interactions. The CV of X display rate is dependent on irreversible and quasi-reversible redox waves in the anodic and cathodic regions due to oxidation and reduction of phenolic and iminic groups, respectively. As evidenced by ESR and UV-vis study, chemical oxidation of X by PbO2 and (NH4)2Ce(NO3)6 in MeCN and CHCl3 generates stable phenoxyl radicals [(g approximately 2.005 and lambda approximately 450 nm (1600-8200 M(-1) cm(-1))]. PMID- 17869168 TI - A novel and selective assay for the quantitative analysis of molybdenum(VI) at nanogram level by resonance light scattering quenching technique. AB - A novel method is designed for the direct determination of trace amounts of molybdenum(VI) in tap water, human hair, and Chinese herbal medicine by means of decreasing resonance light scattering (RLS) technique. The characteristics of RLS spectra, the effective factors, and optimum conditions of the reaction were studied. In the medium of hydrochloric acid (pH 2.38), Mo(VI), dibromohydroxyphenylfluorone (DBHPF), and Triton X-100 react to form a complex, resulting in significant decreasing RLS signals of DBHPF-Triton X-100. The decreasing RLS intensity at 583.0 nm is proportional to the concentration of Mo(VI) up to 8.0 ng mL(-1). The detection limit is 0.013 ng mL(-1). The method is simple, reproducible, with reaction rapidity and stability of complexes formed. Moreover, the high selectivity and sensitivity of this method permits its direct determination of molybdenum(VI) in tap water, human hair, and Chinese herbal medicine and the results are in agreement with those obtained by the inductively coupled plasma atomic emission spectrometry (ICP-AES) method. PMID- 17869169 TI - Diagnosis of human metapneumovirus by immunofluorescence staining with monoclonal antibodies in the North-East of England. AB - BACKGROUND: Since its discovery in 2001 human metapneumovirus (hMPV) has been shown to be a significant cause of human respiratory disease, responsible for 5 8% of respiratory infections in hospitalised children. Diagnosis hitherto has been largely carried out by reverse tanscriptase polymerase chain reaction (RT PCR) but immunofluorescence staining of cells from nasopharyngeal secretions (IF) offers advantages for some laboratories and may produce a more rapid result in urgent cases. We have recently demonstrated that IF with a rabbit antiserum gave sensitivity equal to that of RT-PCR. However, monoclonal antibodies offer a more plentiful, uniform IF reagent. OBJECTIVES: Here we have evaluated a pool of anti hMPV monoclonal antibodies in the routine diagnosis of respiratory infections in hospitalised infants and children. STUDY DESIGN: Eight hundred and fifty-seven routine respiratory specimens were tested by IF with rabbit polyclonal antiserum and monoclonal antibody pool in parallel. A further 1003 specimens were tested with the monoclonal antibody pool alone. All specimens were also tested for a panel of other respiratory viruses by IF. RESULTS: Both rabbit polyclonal antiserum and monoclonal antibody pool gave positive results in 56 and negative results in 797 specimens. The rabbit polyclonal antibody detected virus in a further two specimens which were negative when tested with the monoclonal pool giving a concordance of 96.6% and a specificity of 100% for the monoclonal antibody pool. Overall hMPV was detected in 5% of specimens whilst 18.4% were positive for hRSV. CONCLUSIONS: The monoclonal antibody pool-based IF is a robust assay suitable for routine use with a sensitivity only slightly less than that of the other major diagnostic methodologies available. PMID- 17869171 TI - Growth factors upregulate deposition and remodeling of ECM by endothelial cells cultured for tissue-engineering applications. AB - Appropriate matrix formation, turnover and remodeling in tissue-engineered small diameter vascular conduits are crucial for their long-term function. The interaction between cells and extra-cellular components is indispensable in determining cellular behavior in tissues and on biomaterials. The fibrin that contains fibronectin shows promise in most aspects as a tissue engineering scaffold, whereas, deposition of elastin and collagen by endothelial cells grown in the lumen of the construct is desirable to improve post implant retention, mechanical stability and vaso-responsiveness. So far there is no report on production of extra-cellular matrix (ECM) proteins, elastin and collagen by endothelial cells (EC) in in vitro culture conditions. In this study, we have used a biomimetic approach of providing multiple growth factors (GF) in the fibronectin (FN)-containing fibrin matrix to induce production of elastin and collagen by the endothelial cells for application in vascular tissue engineering. Deposition of elastin and collagens with matrix remodeling is demonstrated through qualitative analysis of the matrices that were recovered after growing cells on the initial fibrin-FN-GF matrix. Expressions of mRNA for both proteins were assessed by real time polymerase chain reaction (RT-PCR) to estimate the effects of multiple growth factor compositions. Marked deposition of elastin and collagen was evidenced by staining the recovered matrix after different culture intervals. Obviously, the biomimetic environment created by adding angiogenic and platelet growth factors in the fibrin-fibronectin-gelatin matrix can induce deposition of collagens and elastin by EC. PMID- 17869170 TI - Detection of a premature stop codon in the surface gene of hepatitis B virus from an HBsAg and antiHBc negative blood donor. AB - BACKGROUND: In blood donors, HBV infection is detected by the presence of serum hepatitis B surface antigen (HBsAg). However, some mutations in the surface gene region may result in altered or truncated HBsAg that can escape from immunoassay based diagnosis. Such diagnostic escape mutants pose a potential risk for blood transfusion services. RESULTS: In the present study, we report a blood donor seronegative for HBsAg and antiHBc, but positive for antiHBs who was HBV DNA positive by PCR. Sequencing of the HBsAg gene revealed presence of a point mutation (T-A) at 207th nucleotide of the HBsAg ORF, which resulted in a premature stop codon at position 69. This results in a truncated HBsAg gene lacking the entire 'a' determinant region. However, follow-up of the donor after 2 years revealed clearance of HBV DNA from the serum. CONCLUSION: The case illustrates an unusual mutation, which causes HBsAg negativity. The finding emphasizes the importance of molecular assays in reducing the possibility of HBV transmission through blood transfusion. However, developing more sensitive serological assays, capable of detecting HBV mutants, is an alternative to expensive and complex amplification-based assays for developing countries. PMID- 17869172 TI - RGD peptides grafting onto poly(ethylene terephthalate) with well controlled densities. AB - The aim of this study was to graft RGD peptides with well controlled densities onto poly(ethylene terephthalate) (PET) film surfaces. Biomimetic modifications were performed by means of a four-step reaction procedure: surface modification in order to create -COOH groups onto polymer surface, coupling agent grafting and finally immobilization of peptides. The originality of this work is to evaluate several grafted densities peptides. Toluidine blue and high-resolution mu-imager (using [(3)H]-Lys) were used to evaluate densities. Moreover, mu-imager has exhibited the stability of peptides grafted onto the surface when treated under harsh conditions. Benefits of the as-proposed method were related to the different concentrations of peptides grafted onto the surface as well as the capacity of RGD peptide to interact with integrin receptors. PMID- 17869173 TI - Spark plasma sintering synthesis of porous nanocrystalline titanium alloys for biomedical applications. AB - The reason for the extended use of titanium and its alloys as implant biomaterials stems from their lower elastic modulus, their superior biocompatibility and improved corrosion resistance compared to the more conventional stainless steel and cobalt-based alloys [Niinomi, M., Hattori, T., Niwa, S., 2004. Material characteristics and biocompatibility of low rigidity titanium alloys for biomedical applications. In: Jaszemski, M.J., Trantolo, D.J., Lewandrowski, K.U., Hasirci, V., Altobelli, D.E., Wise, D.L. (Eds.), Biomaterials in Orthopedics. Marcel Dekker Inc., New York, pp. 41-62]. Nanostructured titanium based biomaterials with tailored porosity are important for cell-adhesion, viability, differentiation and growth. Newer technologies like foaming or low density core processing were recently used for the surface modification of titanium alloy implant bodies to stimulate bone in-growth and improve osseointegration and cell-adhesion, which in turn play a key role in the acceptance of the implants. We here report preliminary results concerning the synthesis of mesoporous titanium alloy bodies by spark plasma sintering. Nanocrystalline cp Ti, Ti-6Al-4V, Ti-Al-V-Cr and Ti-Mn-V-Cr-Al alloy powders were prepared by high-energy wet-milling and sintered to either full-density (cp Ti, Ti-Al-V) or uniform porous (Ti-Al-V-Cr, Ti-Mn-V-Cr-Al) bulk specimens by field assisted spark plasma sintering (FAST/SPS). Cellular interactions with the porous titanium alloy surfaces were tested with osteoblast-like human MG-63 cells. Cell morphology was investigated by scanning electron microscopy (SEM). The SEM analysis results were correlated with the alloy chemistry and the topographic features of the surface, namely porosity and roughness. PMID- 17869174 TI - Emulsion-based synthesis of PLGA-microspheres for the in vitro expansion of porcine chondrocytes. AB - The in vitro cell expansion of autologous chondrocytes is of high interest in regenerative medicine since these cells can be used to treat joint cartilage defects. In order to preserve chondrocyte phenotype, while optimizing adhesion on microspheres, several processing parameters for the microsphere synthesis were varied. In this study three different polylactide-co-glycolides were used with differing lactide-glycolide ratios (85:15 and 50:50) and differing inherent viscosities. An emulsion route was established, where the polymer was dissolved in chloroform and then injected into a stirred polyvinyl alcohol-water solution at different polymer concentrations and different stirring velocities to produce microspheres with varying diameters. The sphere size distribution and morphology was analyzed using image processing software on SEM pictures. Based on previous experiments with commercial microspheres, three optimum samples were selected for further investigations. The degradation of the microspheres was determined in a long-term experiment in culture medium for 3 months. Adherent cells were characterized after 3 and 5 days by FDA+EB vital staining and in SEM. PMID- 17869175 TI - Antibacterial activation of hydroxyapatite (HA) with controlled porosity by different antibiotics. AB - In order to prevent the increasing frequency of per-operative infections, bioceramics can be loaded with anti-bacterial agents, which will release with respect to their chemical characteristics. A novel hydroxyapatite (HA) was elaborated with specific internal porosities for using as a bone-bioactive antibiotic (ATB) carrier material. UV spectrophotometry and bacteria inhibition tests were performed for testing the ATB adsorption and the microbiological effectiveness after loading with different antibiotics. The impregnation time, ATB impregnating concentration, impregnation condition and other factors, which might influence the ATB loading effect, were studied by exposure to different releasing solvents and different pathogenic bacteria: Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli. It clearly showed that the facility of ATB loading on this porous HA is even possible just under simple non vacuum impregnation conditions in a not-so-long impregnating interval. The results also showed that, for all three types of ATB (vancomycin, ciprofloxacin and gentamicin), adsorbed amount on the micro-porous HA were hugely higher than that on dense HA. The micro-porosity of test HA had also significantly prolonged the release time of antibiotics even under mimic physiological conditions. Furthermore, it also has primarily proved by a pilot test that the antibacterial efficiency of crude micro-porous HA could be further significantly improved by other methods of functionalization such as cold plasma technique. PMID- 17869176 TI - Inverse inkjet printed gold micro electrodes for the structured deposition of epithelial cells and fibrin. AB - The micro structured deposition of vital cells is an important challenge in tissue engineering, biosensor technology, and in all research dealing with cell cell and cell-substrate contacts. Hence, an inkjet printing technology has been developed to manufacture Au-based micro electrodes by sputter coating inversely printed polyester-foils. These electrodes feature minimal structure sizes of 35 microm and consist of an anode and a cathode part. They were used with fibrinogenic epithelial cell suspensions to deposit human keratinocytes (HaCaT), mouse fibroblasts (L-929) and the protein fibrin by applying DC voltage. Subsequently cells were electrophoretically attracted to the anode, following exactly its shape, while the insoluble fibrin was simultaneously precipitated due to the electrically mediated polymerization of the soluble fibrinogen molecule. Furthermore, it was demonstrated that this technique is suitable to co-deposit both cell types in a layered fashion. The lower voltage boundary for successful deposition was set at approximately 0.8 V needed for the conversion of fibrinogen into fibrin, while the upper voltage boundary was set at approximately 1.85 V, when commencing electrolysis inhibited the deposition of vital cells. Subsequent to the anodic cell-fibrin deposition, cells were cultivated for up to 4 days and then characterized by FDA+EB staining, methyl violet staining, MNF staining and SEM. The conversion from fibrinogen into fibrin was studied using ATR/FTIR. PMID- 17869177 TI - Tribo-electrochemical technique for studying tribocorrosion behavior of biomaterials. AB - Tribocorrosion is the term which describes the synergy between tribological and electrochemical processes. An apparatus was designed and built to study the tribocorrosion behavior of biomaterials. Electrochemical set-up with three electrodes is used for controlling the potential of the surface of a conducting material subjected to classical wear testing. Using this equipment, it is possible to carry out friction and wear tests in electrolytic solution under well defined electrochemical conditions determined by the applied electrode potential. In this paper, this apparatus was described and the tests of deposited TiN on pure Ti for corrosion and tribocorrosion behavior under simulated body fluid were conducted. The presence of TiN layer on the surface of Ti has increased the open circuit potential. The charge transfer resistance (R(ct)) determined using electrochemical impedance spectroscopy (EIS) was higher for the nitrided surfaces than for the Ti substrates. However after wear test, R(ct) was significantly reduced because the protective layer was damaged. PMID- 17869178 TI - Ti-Cp functionalization by deposition of organic/inorganic silica nanoparticles. AB - In orthopaedics and cardiovascular surgery, titanium has become the metal of choice, due to its excellent mechanical properties and biocompatibility. In many surgical operations, chemicals and/or biomolecules (such as antibiotics or growth factors) are used in conjunction with prostheses, so as to avoid or stimulate targeted biological events. Often, immobilization instead of release of such molecules is preferred to optimize their effects, thus avoiding ectopic transformations. A versatile method for the functionalization of pure Ti is shown here, which allows the covalent immobilization of polypeptides. In order to avoid the hydrolysable Ti-O-Si bond found in directly silanized Ti, we use organic/inorganic silica colloids, derived from commercially available 25 nm Ludox silica nanoparticles. Prior to deposition onto Ti-Cp, the silica nanoparticles are functionalized by a propylsemicarbazide moiety by silanization. After spin-coating onto the Ti substrates, the colloids were shown by SEM to form a uniform layer, and to be very strongly adsorbed; the reactivity of the supported semicarbazide (Sc) functionalities being maintained. Chemoselective reaction of semicarbazide groups on the surface with aldehyde moieties present on the polypeptide of interest was chosen in this work due to its efficiency, to its compatibility with the proteinogenic amino acids and in particular cystein and to the use of mild experimental conditions. Aldehyde groups are also easily introduced onto polypeptides by synthesis, oxidation of N-terminal Ser residue or polysaccharide moieties of glycoproteins. Biological assays with MC3T3-E1 osteoblasts revealed an excellent cytocompatibility as shown by the assessment of cell viability, vitality and morphology. PMID- 17869179 TI - Underestimation of toluene diisocyanate concentration using long-term sampling with 1-(2-methoxyphenyl) piperazine impregnated filters. AB - Occupational exposure to toluene diisocyanate (TDI) is a known occupational hazard and the occupational exposure limits in air are very low. One of the most common methods to monitor exposure to isocyanates is to sample air through filters impregnated with 1-(2-methoxyphenyl) piperazine (2MP). In one earlier field study it was found that long-term sampling with 2MP-filters underestimated the exposure compared with consecutive short-term samples of TDI. The aim of this study was to confirm that finding in a controlled atmosphere in the laboratory. A test atmosphere of 2,4-TDI or 2,6-TDI was generated in a small test chamber and parallel long-term samples and consecutive short-term samples were collected. A total of 159 filters were exposed. The long-term samples collected significantly lower amounts of TDI than the sum of the short-term samples. For a 4-h sampling, the air levels were calculated to underestimate the exposure for 2,4-TDI by a factor of 1.4 and for 2,6-TDI by a of factor 1.3. The calculated underestimation was lower than earlier reported. PMID- 17869180 TI - Survival of epidemic strains of healthcare (HA-MRSA) and community-associated (CA MRSA) meticillin-resistant Staphylococcus aureus (MRSA) in river-, sea- and swimming pool water. AB - The aim of this study was to examine the survival dynamics of several epidemic healthcare (HA) and community-associated (CA) meticillin-resistant Staphylococcus aureus (MRSA) in river, sea and swimming pool waters. Six different phage-types of HA-MRSA (Irish 1, Irish 2, EMRSA 15, EMRSA 16, distinct type and non-typable), as well as a community-associated MRSA (CA-MRSA), were examined in this study. Two strains of each type were examined resulting in a total of 14 organisms being examined. Cells were harvested from overnight cultures of Columbia blood agar (Oxoid) supplemented with 5% [v/v] defibrinated blood to make a 0.5 McFarland inoculum standard. An inoculum of each MRSA isolate was added individually to each water microcosm to give log(10)5 (10(5)) colony forming units (cfu/ml water) and water was stored in the dark at ambient temperature for up to 14 days. Recovery experiments were unable to isolate any of HA- or CA-MRSA in the swimming pool water after 24 h storage. This study demonstrates that all 14 epidemic HA and CA MRSA studied can survive in sea and river water environments up to at least 14 days post inoculation. There was no significant differences in the survival dynamics between CA-MRSA and HA-MRSA in any water environment, but all MRSA died off more quickly in river water, compared to sea water, with decimal (D(10)) reduction values of 3.53 and 7.4 days, for river- and sea water, respectively. This study indicates that contaminated sea and river water may serve as potential reservoirs of HA- and CA-MRSA, if such water sources become contaminated with these organisms. PMID- 17869181 TI - Appraisal of neurobehavioral methods in environmental health research: the developing brain as a target for neurotoxic chemicals. AB - Psychological tests as developed and validated in the field of differential psychology have a longstanding tradition as tools to study individual differences. In clinical neuropsychology, global or more specific tests are used as neuropsychological tools in the differential diagnosis of various forms of brain damage or neurobehavioral dysfunction following chemical insults, such as mental sequelae of prenatal alcohol consumption by pregnant mothers (fetal alcohol syndrome) or of maternal thyroid deficiency during pregnancy. Psychometric tests are constructed to fulfill basic quality criteria, namely objectivity, reliability and validity. For strictly diagnostic purposes in individual cases they must also possess normative values based on representative reference groups. Intelligence tests or their developmental variants are often used as endpoints in environmental health research for studying neurodevelopmental adversity due to early exposure to neurotoxic chemicals in the environment. Intelligence as treated in psychology is a complex construct made up of specific cognitive functions which usually cover verbal, numerical and spatial skills, as well as perceptual speed, memory and reasoning. In this paper, case studies covering neurodevelopmental adversity of inorganic lead, of methylmercury and of polychlorinated biphenyls (PCBs) are reviewed, and the issue of postnatal behavioral sequelae of prenatal exposure is covered. In such observational studies precautions must be taken in order to avoid pitfalls of causative interpretation of associations between exposure and neurobehavioral outcome. This requires consideration of co-exposure and confounding. Important confounders considered in most modern developmental cohort studies are maternal intelligence and quality of the home environment. PMID- 17869182 TI - The effect of a physical activity education programme on physical activity, fitness, quality of life and attitudes to exercise in obese females. AB - Obesity has reached epidemic proportions worldwide. Decline in physical activity has occurred simultaneously or before the increase in obesity. The aim of this pilot study was to investigate the effect of a physical activity group-based education programme delivered by a Physiotherapist on weight, physical activity, cardiovascular fitness, quality of life and attitudes to exercise in obese females. A sample of 18 obese Irish females (mean age 37.6 years, mean weight 117.9kg), took part in this study. The participants attended four physical activity education sessions in groups of 6-8, 1 month apart. Outcome measures were Cardiorespiratory fitness (CRF) measured by the Incremental Shuttle Walk test (ISWT) International Physical Activity Questionnaire-Short Form (IPAQ-Short) Impact of Weight on Quality of Life Questionnaire-Short Form (IWQOL-Lite), and a questionnaire adapted from the EU survey on Consumer Attitudes to Physical Activity. There were no significant decreases in participants' weight (p=0.444) and there were no significant improvements in IPAQ (p=0.496) and IWQOL-Lite scores (p=0.337). There were significant improvements in CRF (p<0.0002). Attitudes towards exercise improved as shown by decreased barriers to exercise, i.e. decreased shyness (17%) and increased energy (22%) and increased enjoyment (22%). A group education programme focusing on physical activity alone demonstrated a significant increase in CRF (ISWT) and had a positive influence on attitudes to exercise. Longer duration interventions may allow participants to make the necessary lifestyle changes to achieve weight loss. PMID- 17869183 TI - Maximising performance in triathlon: applied physiological and nutritional aspects of elite and non-elite competitions. AB - Triathlon is a sport consisting of sequential swimming, cycling and running. The main diversity within the sport of triathlon resides in the varying event distances, which creates specific technical, physiological and nutritional considerations for athlete and practitioner alike. The purpose of this article is to review physiological as well as nutritional aspects of triathlon and to make recommendations on ways to enhance performance. Aside from progressive conditioning and training, areas that have shown potential to improve triathlon performance include drafting when possible during both the swim and cycle phase, wearing a wetsuit, and selecting a lower cadence (60-80 rpm) in the final stages of the cycle phase. Adoption of a more even racing pace during cycling may optimise cycling performance and induce a "metabolic reserve" necessary for elevated running performance in longer distance triathlon events. In contrast, drafting in swimming and cycling may result a better tactical approach to increase overall performance in elite Olympic distance triathlons. Daily energy intake should be modified to reflect daily training demands to assist triathletes in achieving body weight and body composition targets. Carbohydrate loading strategies and within exercise carbohydrate intake should reflect the specific requirements of the triathlon event contested. Development of an individualised fluid plan based on previous fluid balance observations may assist to avoid both dehydration and hyponatremia during prolonged triathlon racing. PMID- 17869184 TI - COX-2 expression in B lymphocytes: links to vaccines, inflammation and malignancy. PMID- 17869185 TI - Impact of interictal epileptic activity on normal brain function in epileptic encephalopathy: an electroencephalography-functional magnetic resonance imaging study. AB - Using electroencephalography (EEG) in combination with functional magnetic resonance imaging (fMRI), we studied a 9.5-year-old girl who developed cognitive and behavioral regression in association with intense interictal bilaterally synchronous epileptic discharges (IBSEDs) both during the awake state and during sleep. During runs of IBSEDs, EEG-fMRI demonstrated deactivations in the lateral and medial frontoparietal cortices, posterior cingulate gyrus, and cerebellum together with focal relative activations in the right frontal, parietal, and temporal cortices. The deactivations probably reflect the repercussion of the interictal epileptic activity on normal brain function which might cause the neuropsychological regression by inducing repetitive interruptions of neurophysiological function resulting in a chronic state of specific psychomotor impairment. The relative activations could possibly indicate the source of epileptic activity rapidly spreading to other brain regions. PMID- 17869186 TI - Does the concept of emotional intelligence contribute to our understanding of temporal lobe resections? AB - Research on temporal lobe (TL) resection has revealed impairments in cognition and emotion that differ as a function of laterality. Until recently, however, a construct called "emotional intelligence" had not been investigated in surgical recipients. We asked if Bar-On's Emotional Quotient Inventory (EQ-i) was sensitive to the side of the temporal lobe lesion, and if the EQ-i correlated with intellectual and psychosocial functioning. EQ-i scores, estimated Full Scale IQ, verbal memory, confrontation naming, and psychosocial adjustment data were analyzed for 38 patients who underwent TL resection. Results indicated that the EQ-i self-ratings were significantly lower than the average-range Full Scale IQ. Verbal memory and naming skills were significantly worse after left than right TL resection, but EQ-i scores did not reflect a laterality effect. The EQ-i correlated significantly with psychosocial adjustment, but not with estimated Full Scale IQ. We concluded that there was no compelling evidence for lateral specialization of EI, although it seems to be a theoretically relevant construct that may be useful in understanding individuals with epilepsy. PMID- 17869187 TI - Down-regulation of endogenous nitric oxide synthase inhibitors on endothelial SK3 expression. AB - OBJECTIVES: To investigate role of endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) in down-regulation of the expression of endothelial SK3 in atherosclerosis. METHODS: Apolipoprotein E deficient (apo E(-/ )) mice aged 11 approximately 12 weeks were treated with ADMA (5 mg/kg per day, subcutaneous injection) for 4 weeks. Cultured human umbilical venous endothelial cells (HUVECs) were treated with different concentrations of lysophosphatidylcholine (LPC) or ADMA for 48 h. Plasma levels of ADMA were determined by high performance liquid chromatogram (HPLC); protein and mRNA levels of SK3 in the aortas of mice and cultured cells were detected by immunofluorescence, western blot and RT-PCR, respectively. RESULTS: Concomitantly with the elevated plasma levels of ADMA, the expressions of both SK3 protein and mRNA in aortas of apo E(-/-) mice were significantly reduced in comparison to those of the wild-type mice. Moreover, 4-week treatment of ADMA made levels of SK3 expression even lower. In cultured HUVECs, either LPC or ADMA notably decreased the expressions of both SK3 protein and mRNA in a concentration dependent manner. CONCLUSIONS: Endogenous ADMA may be an important factor for down-regulation of the expression of endothelial SK3 in atherosclerotic animals. PMID- 17869188 TI - Pharyngeal motor control and the pathogenesis of obstructive sleep apnea. AB - The upper airway in patients with obstructive sleep apnea (OSA) is thought to collapse during sleep at least in part, because of a sleep related reduction in upper airway dilator muscle activity. Therefore, a comprehensive understanding of the neural regulation of these muscles is warranted. The dilator muscles can be classified in two broad categories; those that have respiratory related activity and those that fire constantly throughout the respiratory cycle. The motor control of these two groups likely differs with the former receiving input from respiratory neurons and negative pressure reflex circuits. The activity of both muscle groups is reduced shortly after sleep onset, indicating that both receive input from brainstem neurons involved in sleep regulation. In the apnea patient, this may lead to pharyngeal airway collapse. This review briefly describes the currently proposed sleep and respiratory neural pathways and how these circuits interact with the upper airway dilator muscle motorneurones, including recent evidence from animal studies. PMID- 17869189 TI - Gender differences in age and BMI distributions in partial upper airway obstruction during sleep. AB - The obstructive sleep apnea-hypopnea syndrome occurs more frequently and with higher apnea-hypopnea indices in men than in women. To investigate the gender differences we extended our respiratory analyses during sleep to cover not only periodic obstruction (apnea and hypopnea) but also nonperiodic partial upper airway obstruction during sleep and their associations with increasing age or body mass index (BMI). The clinical sleep recordings with the static-charge sensitive bed (SCSB) and oximeter were reviewed in 233 age and BMI-matched men women pairs. Periodic obstruction increased with increasing BMI only in men. Nonperiodic partial obstruction increased with moderate to morbid obesity in women and men after the age of 65 years. Our findings suggest that while partial upper airway obstruction increases with increasing age and BMI in both genders, men have a gender specific BMI dependent predisposition for periodic obstruction (obstructive sleep apnea). The apnea-hypopnea index is likely to underestimate the impact of sleep-disordered breathing, particularly in elderly patients. PMID- 17869190 TI - Ventilatory responses to acute hypoxia in neurokinin-1 receptor deficient mice. AB - The regulatory effect of substance P on respiration is mediated via neurokinin (NK) receptors. While previous studies suggest that NK-1 receptors are involved, little is known about the role NK-2 receptors in ventilatory responses to hypoxia. Ventilatory responses to acute hypoxia (8% O2 in N2) were measured by indirect plethysmography in unanaesthetized, unrestrained NK-1 receptor gene deficient (NK-1-/-) and wild-type mice. In additional experiments mice were treated with an NK-2 receptor antagonist prior to hypoxic challenge. Resting ventilatory parameters were not different between groups. NK-1-/- mice displayed significantly greater shortening of expiratory time and higher increase of breathing frequency during hypoxia than wild-type mice. Treatment with the NK-2 receptor antagonist SR 48968 (1 mg/kg) resulted in a further shortening of inspiratory and expiratory time in NK-1-/- but not wild-type mice. These results demonstrate that both NK-1 and NK-2 receptors are involved in the modification of ventilation in response to acute hypoxia. PMID- 17869191 TI - Spontaneous central apneas occur in the C57BL/6J mouse strain. AB - Despite the clinical significance of central apneas in a wide range of disorders little is known about their pathogenesis. Research in this field has been hindered by the lack of appropriate animal models. Our goal was to determine whether the C57BL/6J mouse strain, which has an inherited predisposition for dysrhythmic breathing, exhibits spontaneous apneas. In vivo plethysmography of unanesthetized, unrestrained adult C57BL/6J mice revealed a regular occurrence of spontaneous apneas. In situ recordings from respiratory outputs (phrenic, vagal, hypoglossal nerves) in the working heart-brainstem preparation (WHBP) also showed spontaneous central apneas accompanied by laryngeal closure as indicated by tonic vagal postinspiratory activity and increase in subglottal pressure. The apneas were further characterized by a hypoglossal discharge with delayed onset compared to the tonic vagal postinspiratory activity. We conclude that spontaneous central apneas with active laryngeal closure occur in C57BL/6J mice. This mouse strain is a useful animal model to study neuronal mechanisms that underlie the generation of spontaneous central apneas. PMID- 17869192 TI - The enigma of aestivation in the African lungfish Protopterus dolloi--commentary on the paper by Perry et al. PMID- 17869193 TI - Simultaneous estimation of mangiferin and four secoiridoid glycosides in rat plasma using liquid chromatography tandem mass spectrometry and its application to pharmacokinetic study of herbal preparation. AB - Extracts from Swertia chirata (family Gentianaceae) have antidiabetics and antioxidant activity, largely attributed to the flavonoids and secoiridoids, which are a major class of functional components in methanolic extracts from aerial part of plants. In order to facilitate analysis of systemic exposure to S. chirata derived products in animals, we developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) based method that is capable of routinely monitoring plasma levels of flavonoids and secoiridoids. An LC-MS/MS-based method has been developed for the simultaneous estimation of two bioactive markers, mangiferin and amarogentin along with three other components, amaroswerin, sweroside and swertiamarin in rat plasma. All the analytes including the internal standard (kutkoside) were chromatographed on RP-18 column (250 mm x 4 mm i.d., 5 microm.) coupled with guard column using acetonitrile: 0.5 mM ammonium acetate buffer, pH approximately 3.0 as mobile phase at a flow rate of 1 ml/min in gradient mode. The final flow to source was splitted in 1:1 ratio. The detection of the analytes was performed on API 4000 LC-MS/MS system in the multiple reaction-monitoring (MRM) mode. The quantitation for analytes other than the pure markers was based on relative concentration. The method was validated in terms of establishing linearity, specificity, sensitivity, recovery, accuracy and precision (Intra- and Inter-day), freeze-thaw stability, peltier stability, dry residue stability and long-term stability. The recoveries from spiked control samples were >90% for all analytes and internal standard except mangiferin where recovery was >60%. Intra- and inter-day accuracy and precision of the validated method were within the acceptable limits of <15% at low and <10% at other concentrations. The quantitation method was successfully applied to generate pharmacokinetic (PK) profile of markers as well as to detect other components in plasma after intravenous dose administration of herbal preparation in male Sprague-Dawley (SD) rats. PMID- 17869194 TI - Anti Zn antibodies: cross reactivity and competitive binding with heavy metals. AB - Monoclonal antibodies of IgM class, specific to IDA-Zn were used for evaluating their Zn(2+) binding efficiency in the presence of trace metal ions such as Cr(3+) Cr(6+), Cu(2+) and Cd(2+). In the present work, antibody raised against the hapten IDA-Zn(II) was pre-incubated with different metal ions and the binding capacity to the specific hapten was tested using ELISA and immobilized metal ion affinity chromatography (IMAC) techniques. IMAC was carried out with the free antibody and antibody pre-incubated with selected heavy metal ions using Sepharose IDA-Zn(2+) column and the same samples were tested using a hapten specific ELISA with non-protein hapten carrier. Different effects were observed after pre-incubation with metal ions. Cr(3+) exhibited synergistic binding where as antagonism was detected with Cd(2+). The synergistic effect observed with Cr(3+) suggests involvement of binding sites other than that of zinc and conformational changes that result from Cr(3+) binding. It is probable that, this binding event also increases the accessibility of the zinc binding sites on IgM. On the same lines, the antagonism observed with Cd(2+) could be attributed to structural changes resulting in reduced accessibility to zinc binding sites. In case of Cr(6+), no appreciable change in binding to IDA-Zn was observed while Cu(2+) showed competitive binding. PMID- 17869195 TI - Mycobacterial Ser/Thr protein kinases and phosphatases: physiological roles and therapeutic potential. AB - Reversible protein phosphorylation is a major regulation mechanism of fundamental biological processes, not only in eukaryotes but also in bacteria. A growing body of evidence suggests that Ser/Thr phosphorylation play important roles in the physiology and virulence of Mycobacterium tuberculosis, the etiological agent of tuberculosis. This pathogen uses 'eukaryotic-like' Ser/Thr protein kinases and phosphatases not only to regulate many intracellular metabolic processes, but also to interfere with signaling pathways of the infected host cell. Disrupting such processes by means of selective inhibitors may thus provide new pharmaceutical weapons to combat the disease. Here we review the current knowledge on Ser/Thr protein kinases and phosphatases in M. tuberculosis, their regulation mechanisms and putative substrates, and we explore their therapeutic potential as possible targets for the development of new anti-mycobacterial compounds. PMID- 17869196 TI - Bowman-Birk protease inhibitor from the seeds of Vigna unguiculata forms a highly stable dimeric structure. AB - Different protease inhibitors including Bowman-Birk type (BBI) have been reported from the seeds of Vigna unguiculata. Protease isoinhibitors of double-headed Bowman-Birk type from the seeds of Vigna unguiculata have been purified and characterized. The BBI from Vigna unguiculata (Vu-BBI) has been found to undergo self-association to form very stable dimers and more complex oligomers, by size exclusion chromatography and SDS-PAGE in the presence of urea. Many BBIs have been reported to undergo self-association to form homodimers or more complex oligomers in solution. Only one dimeric crystal structure of a BBI (pea-BBI) is reported to date. We report the three-dimensional structure of a Vu-BBI determined at 2.5 A resolution. Although, the inhibitor has a monomer fold similar to that found in other known structures of Bowman-Birk protease inhibitors, its quaternary structure is different from that commonly observed in this family. The structural elements responsible for the stability of monomer molecule and dimeric association are discussed. The Vu-BBI may use dimeric or higher quaternary association to maintain the physiological state and to execute its biological function. PMID- 17869197 TI - Improving the activity and stability of thermolysin by site-directed mutagenesis. AB - In previous site-directed mutagenesis study on thermolysin, mutations which increase the catalytic activity or the thermal stability have been identified. In this study, we attempted to generate highly active and stable thermolysin by combining the mutations so far revealed to be effective. Three mutant enzymes, L144S (Leu144 in the central alpha-helix located at the bottom of the active site cleft is replaced with Ser), G8C/N60C/S65P (Gly8, Asn60, and Ser65 in the N terminal region are replaced with Cys, Cys, and Pro, respectively, to introduce a disulfide bridge between the positions 8 and 60), and G8C/N60C/S65P/L144S, were constructed by site-directed mutagenesis. In the hydrolysis of N-[3-(2 furyl)acryloyl]-glycyl-L-leucine amide (FAGLA) and N-carbobenzoxy-L-aspartyl-L phenylalanine methyl ester (ZDFM), the k(cat)/K(m) values of L144S and G8C/N60C/S65P/L144S were 5- to 10-fold higher than that of the wild-type enzyme. The rate constants for thermal inactivation at 70 degrees C and 80 degrees C of G8C/N60C/S65P and G8C/N60C/S65P/L144S decreased to 50% of that of the wild-type enzyme. These results indicate that G8C/N60C/S65P/L144S is more active and stable than the wild-type thermolysin. Thermodynamic analysis suggests that the single mutation of Leu144-->Ser and the triple mutation of Gly8-->Cys, Asn60-->Cys, and Ser65-->Pro are independent. PMID- 17869198 TI - Treatment of high output entero-cutaneous fistulae associated with large abdominal wall defects: single center experience. AB - BACKGROUND AND AIM: Enteric fistulas are defined by their sites of origin, communication and flow. We evaluate the treatment of complex patients with entero cutaneous fistulae with large abdominal wall defects. MATERIALS AND METHODS: Retrospective case note review of 19 patients (15 males, median age 46 years) treated at the Department of Surgical Sciences, University of Insubria, Varese, Italy. These were distinguished by multiple/wide gastrointestinal fistula orifices, with total discontinuity of bowel. Fistulas were not covered by abdominal wall thus presenting with a giant abdominal wall defects. Surgery was planned once adequate nutritional status was present. RESULTS: All fistulas resulted from previous surgery for IBD in 7 cases (37%), abdominal trauma 4 (21%), acute necrotic infected pancreatitis 3 (16%), intra-abdominal malignancy 3 (16%), and diverticular disease 2 (10%). The most common site of presentation was ileum (80%). Median fistula output was 800ml/day (range 400-1600ml/day). Seltzer's prognostic index identified malnutrition in 70% of patients at the time of presentation. The elapsed mean time from onset of fistula and elective time of surgical management were 184 days (range 20-2190 days). The VAC system was used in the last 7 patients preoperatively and in 6 patients with postoperative abdominal wound dehiscences that could not be closed immediately and who were at high risk for healing complications. There were no complications from the VAC therapy. Surgery was successful in 69% of cases. Mortality rate was 21%. Factors related to mortality were persistent malignancy, malnutrition and sepsis. CONCLUSIONS: After optimization of nutritional status surgery with en bloc resection of fistula offers best results. In this series, cancer and sepsis were unfavourable factors for outcome. These fistulas may be successfully managed with a multidisciplinary approach. PMID- 17869199 TI - Decision making in laparoscopic surgery: a prospective, independent and blinded analysis. AB - AIMS: Correct decision making is pivotal and an integral part of surgical competency. To date there has not been an attempt to assess surgeons making decisions whilst operating. In our present study we aim to assess operative decision making by trainee and expert surgeons by using hierarchical task analysis (HTA) as a method to map out decision making in surgery. METHODS: One hundred and forty live laparoscopic operations were prospectively analyzed, independently and blindly. The operations were compared to an operative HTA, and individual case reasons for deviations noted. Factors in the operating theatre which may influence the surgeons' decisions whilst operating were assessed using a checklist. RESULTS: One hundred and nineteen elective and 21 emergency laparoscopic operations performed by 12 consultants and 14 registrars were analysed. Factors from the HTA and theatre environment checklists were categorised. Inter-rater reliability was k=0.95, k=1.00 for sub-tasks and tasks, respectively, and 0.98 between the surgeon and independent observer for the operating theatre checklist. From these data sets a psychomotor surgical decision making model was constructed. Face and content validities of the model were verified by experts in surgery and decision making. CONCLUSIONS: Dynamic surgical decision making is a multi-faceted and intricate process. We have used HTA to map this process and we present a model in surgical decision making. By understanding the mechanisms and factors which influence this process we may use it for effective, focused surgical training. We aim to use and test our model also on open major complex surgery. PMID- 17869200 TI - Initial experiences using non-cultured autologous keratinocyte suspension for burn wound closure. AB - Early complete wound closure and thus reduction of excessive scar formation still represent a major clinical challenge in severely burned patients. A novel concept to cover large burn wounds consists of the application of non-cultured epithelial cell suspension within the first days. Herein, we report our experiences with three patients treated with CellSpray XP. According to the amount of cell suspension required, a skin biopsy was harvested and then processed in an external laboratory. Two days later the suspension containing autologous non cultured keratinocytes was applied using an aerosol system. All wounds healed rapidly and virtually no signs of hypertrophic scarring were observed 6 months later. PMID- 17869201 TI - Mechanical regulation of PTHrP expression in entheses. AB - The PTHrP gene is expressed in the periosteum and in tendon and ligament insertion sites in a PTHrP-lacZ knockin reporter mouse. Here, we present a more detailed histological evaluation of PTHrP expression in these sites and study the effects of mechanical force on PTHrP expression in selected sites. We studied the periosteum and selected entheses by histological, histochemical, and in situ hybridization histochemical techniques, and tendons or ligaments were unloaded by tail suspension or surgical transection. In the periosteum, PTHrP is expressed in the fibrous layer and the type 1 PTH/PTHrP receptor (PTH1R) in the subjacent cambial layer. PTHrP has distinct temporospatial patterns of expression in the periosteum, one hot spot being the metaphyseal periosteum in growing animals. PTHrP is also strongly expressed in a number of fibrous insertion sites. In the tibia these include the insertions of the medial collateral ligament (MCL) and the semimembranosus (SM). In young animals, the MCL and SM sites display a combination of underlying osteoblastic and osteoclastic activities that may be associated with the migration of these entheses during linear growth. Unloading the MCL and SM by tail suspension or surgical transection leads to a marked decrease in PTHrP/lacZ expression and a rapid disappearance of the subjacent osteoblastic population. We have not been able to identify PTHrP-lacZ in any internal bone cell population in the PTHrP-lacZ knockin mouse in either a CD-1 or C57Bl/6 genetic background. In conclusion, we have identified PTHrP expression in surface structures that connect skeletal elements to each other and to surrounding muscle but not in intrinsic internal bone cell populations. In these surface sites, mechanical force seems to be an important regulator of PTHrP expression. In selected sites and/or at specific times, PTHrP may influence the recruitment and/or activities of underlying bone cell populations. PMID- 17869202 TI - Attentional switching in the sequential flanker task: age, location, and time course effects. AB - The sequential flanker task was developed to study sequential performance using methodology borrowed from studies of task switching. We investigated age differences in backward inhibition [BI: Mayr, U., & Keele, S. W. (2000). Changing internal constraints on action: The role of backward inhibition. Journal of Experimental Psychology: General, 129, 4-26] during a sequential category search task. Participants learned four animal categories in a fixed order, and then searched for exemplars from those categories in runs of mis-ordered exemplars. Across three experiments, we observed robust BI facilitation effects. However, the magnitude of BI effects did not differ across age groups. This age-invariance held despite manipulations of distractibility (Experiment 2), and interstimulus interval (Experiment 3), suggesting that BI processes may be relatively automatic and obligatory in the context of sequential tasks. The findings are discussed in terms of the attentional mechanisms that underlie task set switching and sequential performance. PMID- 17869203 TI - Confocal microscopy of colloidal particles: towards reliable, optimum coordinates. AB - Over the last decade, the light microscope has become increasingly useful as a quantitative tool for studying colloidal systems. The ability to obtain particle coordinates in bulk samples from micrographs is particularly appealing. In this paper we review and extend methods for optimal image formation of colloidal samples, which is vital for particle coordinates of the highest accuracy, and for extracting the most reliable coordinates from these images. We discuss in depth the accuracy of the coordinates, which is sensitive to the details of the colloidal system and the imaging system. Moreover, this accuracy can vary between particles, particularly in dense systems. We introduce a previously unreported error estimate and use it to develop an iterative method for finding particle coordinates. This individual-particle accuracy assessment also allows comparison between particle locations obtained from different experiments. Though aimed primarily at confocal microscopy studies of colloidal systems, the methods outlined here should transfer readily to many other feature extraction problems, especially where features may overlap one another. PMID- 17869204 TI - Anti-angiogenic effects of ribonucleic acid interference targeting vascular endothelial growth factor and hypoxia-inducible factor-1alpha. AB - PURPOSE: To compare the in vitro anti-angiogenic effects of inhibiting vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1-alpha (HIF 1alpha) using ribonucleic acid (RNA) interference (RNAi). DESIGN: Laboratory investigation. METHODS: VEGF or HIF-1alpha was antagonized in human retinal pigment epithelial (RPE) cells using RNAi, and then cells were cultured under hypoxia. Angiogenic proteins secreted into the media were measured using enzyme linked immunosorbent assay. Media from hypoxic RPE cells was used to grow human umbilical vein endothelial cells (HUVECs). Capillary tube formation by HUVECs was quantified and compared to assess the effectiveness of angiogenesis. RESULTS: RNAi targeting VEGF caused a significant decrease in VEGF in addition to several other clinically important angiogenic factors, including angiogenin, interleukin 6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and tumor growth factor beta(1) (TGF-beta(1)). Although HIF-1alpha RNAi reduced the production of VEGF, angiogenin, and TGF-beta(1), we observed an increase in the levels of several other angiogenic factors like IL-6, IL-8, and MCP-1. RNAi of VEGF and HIF-1alpha was effective in inhibiting angiogenesis, although the effect was more pronounced for VEGF RNAi. CONCLUSIONS: RNAi of VEGF and HIF-1alpha may have therapeutic potential in ischemic retinal diseases like diabetic retinopathy. Targeting VEGF seems to have the advantage of decreasing the production of several clinically important angiogenic factors, thereby effectively inhibiting angiogenesis. Antagonism of HIF-1alpha may lead to the overactivation of alternate transcription factors and their respective gene products, leading to less effective inhibition of angiogenesis. PMID- 17869205 TI - Diverse clinical presentations of orbital sarcoid. AB - PURPOSE: To review the clinical presentation, location, systemic features, management, and natural history of orbital sarcoid. DESIGN: Retrospective, noncomparative, interventional case series. METHODS: Twenty patients with sarcoid and sarcoidal reactions of the orbit underwent biopsy, excision of localized mass, and systemic and local treatment at a tertiary referral center. Age, gender, onset, symptoms and signs, characterization of disease process, location, systemic disease, associated systemic features, management, and recurrence of the disease were identified. RESULTS: Of the 20 patients studied, five were male and 15 were female. The mean age was 50.55 +/- 16.43 years (range, 18 to 77 years). The most common symptom was the presence of a palpable mass, followed by eyelid swelling. Review of the computed tomographic scans revealed four main categories of presentation: lacrimal gland infiltration (n = 11; 55%), orbital mass (n = 4; 20%), optic nerve sheath and dural involvement (n = 4; 20%), and extraocular muscle involvement (n = 1; 5%). Concurrent systemic sarcoidosis discovered after the diagnosis of orbital sarcoid was present in 10 cases (50%). The remaining showed no evidence of systemic disease at follow-up. Angiotensin converting enzyme analysis was performed in 10 cases; in only two (20%) was elevated, and in the remaining eight, it was within normal levels. CONCLUSIONS: Orbital sarcoid has a diverse clinical presentation varying from lacrimal gland infiltration, soft tissue orbital mass, intraorbital and extraorbital optic nerve sheath and dural involvement, to extraocular muscle involvement. The orbital site most commonly involved was the lacrimal gland. PMID- 17869206 TI - Relationship of axial length and retinal vascular caliber in children. AB - PURPOSE: Previous studies in older adults suggest that longer axial length is associated with narrower arteriolar caliber. In this study, we re-examined this relationship in a cohort of children, while controlling for the effects of ocular magnification. DESIGN: Cross-sectional study of 767 children aged 7 to 9 years. METHODS: Retinal vascular calibers were measured from retinal photographs using a computer-based program. Ocular magnification was corrected using the Bengtsson formula. Standardized examination of refraction and ultrasound ocular biometry was performed for all children. RESULTS: In models that adjusted for age, gender, ethnicity, body mass index, blood pressure, and birth weight, longer axial length was associated strongly with narrower retinal arteriolar caliber (3.18-microm decrease per standard deviation increase in axial length; P < .001) and venular caliber (4.62-microm decrease standard deviation increase in axial length; P < .001) before correction for ocular magnification. However, after correction, these associations no longer were significant (0.44 microm; P = .31, change for arteriolar caliber; and 0.70 microm; P = .25, for venular caliber). CONCLUSIONS: Our study in children found no association between axial length and retinal vascular caliber after correcting for ocular magnification, suggesting that the previously reported association was likely related to differences in ocular magnification. PMID- 17869207 TI - Optical coherence tomography findings in persistent diabetic macular edema: the vitreomacular interface. AB - PURPOSE: To assess the optical coherence tomography (OCT) characteristics of eyes with persistent clinically significant diabetic macular edema (PDME) after focal laser treatment, with emphasis on the vitreomacular interface (VMI) characteristics. DESIGN: Prospective, observational case series. METHODS: Fifty eyes with PDME after at least one focal laser treatment were enrolled prospectively. Slit-lamp biomicroscopy, stereoscopic fundus photography, fluorescein angiography (FA), and OCT were performed for each eye. The main outcome measures included the detection rate of VMI abnormalities (VMIA) by OCT in comparison with biomicroscopy, fundus photography, and FA (traditional techniques); the relationship between VMIA and the number of focal laser sessions per eye and FA leakage pattern. RESULTS: Two of 50 eyes were excluded because of incomplete data. For the remaining 48 eyes, 25 eyes (52.1%) demonstrated definite VMIA, including anomalous vitreal adhesions, epiretinal membrane (ERM), or both, and six eyes (12.5%) had questionable VMIA. OCT in general was 1.94 times more sensitive than traditional techniques combined in detecting VMIA (P = .00003). The number of focal laser sessions and diffuse FA leakage were not associated with an increased prevalence of VMIA (P = .13 and P = .47, respectively). CONCLUSIONS: This study demonstrates a high prevalence of VMIA in eyes with PDME after focal laser treatment and underscores the superiority of OCT in detecting these abnormalities. OCT evaluation of eyes with PDME may be helpful in identifying VMIA, which may impact treatment selection and patient subgroup stratification. PMID- 17869208 TI - Reproducibility and repeatability of central corneal thickness measurement in keratoconus using the rotating Scheimpflug camera and ultrasound pachymetry. AB - PURPOSE: To assess repeatability, reproducibility, and agreement of rotating Scheimpflug camera (Pentacam Oculus, Wetzlar, Germany) and ultrasound pachymetry in measuring central thickness of keratoconic corneas. DESIGN: Method-comparison study. METHODS: In 33 patients with keratoconus (one eye per patient), two examiners each used both pachymetric methods to measure central corneal thickness (CCT); in the same session, measurements then were repeated by examiner 1 (A.M.). The difference between two examiners, and between first and second measurements by examiner 1, with both methods and the difference between the two pachymetric methods in measuring central thickness of keratoconic corneas were noted. RESULTS: With the rotating Scheimpflug camera, interexaminer correlation was higher (intra-class correlation coefficient [ICC], 0.98 vs 0.76) and inter examiner variability was lower (95% limits of agreement [95% LoA], -14.8 to 13.8 microm vs -18.0 to +49.5 microm) than with ultrasound pachymetry. Both methods showed close first- to second-measurement correlation (ICC, > 90), but the rotating Scheimpflug camera had lower variability (95% LoA, -14.5 to 14.2 microm vs -27.4 to 26.0 microm). Mean CCT was 478.9 +/- 34.6 microm with the rotating Scheimpflug camera and 486.6 +/- 30 microm with ultrasound pachymetry. Although the mean difference was small (-7.8 microm), the 95% LoA (-43.8 to 28.2 microm) showed that the difference between the two methods can be considerable. CONCLUSIONS: In keratoconic corneas, the rotating Scheimpflug camera provides measurements of central thickness that are more reproducible and repeatable than those obtained with ultrasound pachymetry. The rotating Scheimpflug camera seems to be suitable for disease staging and follow-up, when corneal thickness measurements may be repeated over time by different examiners. PMID- 17869209 TI - Quantitative DNA hybridization in solution using magnetic/luminescent core-shell nanoparticles. AB - Nanoscale magnetic/luminescent core-shell particles were used for DNA quantification in a hybridization-in-solution approach. We demonstrated a rapid, simple, and non-polymerase chain reaction-based DNA hybridization-in-solution assay for quantifying bacteria capable of biodegrading methyl tertiary-butyl ether. Fe3O4/Eu:Gd2O3 core-shell nanoparticles synthesized by spray pyrolysis were biofunctionalized with NeutrAvidin. Following immobilization of a biotinylated probe DNA on the particles' surfaces via passive adsorption, target DNA labeled with fluorescein isothiocyanate was hybridized with probe DNA. The hybridized DNA complex was separated from solution with a magnet, while nonhybridized DNA remained in solution. The normalized fluorescence (fluorescein isothiocyanate/nanoparticles) measured with a spectrofluorometer indicated a linear quantification (R(2)=0.98) of the target bacterial 16 S rDNA. The rate of hybridization increased concurrently with the target DNA concentration. In addition, this approach differentiated between the signal outputs from perfectly complementary target and two-base mismatched target DNA in a range of concentrations, showing the specificity of the assay and the possibility for environmental applications. PMID- 17869210 TI - A sensitive fluorescence intensity assay for deubiquitinating proteases using ubiquitin-rhodamine110-glycine as substrate. AB - The dynamic modification of proteins with ubiquitin is a key regulation paradigm in eukaryotic cells that controls stability, localization, and function of the vast majority of intracellular proteins. Here we describe a robust fluorescence intensity assay for monitoring the enzymatic activity of deubiquitinating proteases, which reverse ubiquitin modifications and comprise over 100 members in humans. The assay was developed for the catalytic domain of human ubiquitin specific protease 2 (USP2) and human ubiquitin carboxyterminal hydrolase L3 (UCH L3), and makes use of the novel substrate ubiquitin-rhodamine110-glycine. The latter combines the advantages of a high dynamic range and beneficial optical properties. Its enzymatic behavior is characterized by the kinetic constants K(m)=1.5 microM, k(cat) = 0.53s(-1) and k(cat)/K(m) = 3.5 x 10(5)M(-1) s(-1) for USP2 and K(m) = 34 nM, k(cat)=4.72s(-1), and k(cat)/K(m) = 1.4 x 10(8)M(-1) s(-1) for UCH-L3. This new assay is suitable for inhibitor screening and characterizations, and has been established for the 384-well plate format using protease concentrations of 120 pM for USP2 and 1 pM for UCH-L3 and substrate concentrations of 100 nM for both enzymes. Due to the low protease concentrations and high sensitivity, this assay would allow the determination of inhibitory constants in the subnanomolar range. PMID- 17869211 TI - Proteomic analysis of the amyloid precursor protein fragment C99: expression in yeast. AB - The accumulation and aggregation of fragments of amyloid precursor protein (APP) are central to the development of Alzheimer's disease. The production of the small fragment C99 is thought to form the rate-limiting step in the APP processing pathway, which can lead to the production of the toxic Abeta peptide. It has also been suggested that the proteasome contributes to APP catabolism. While the identities and aggregation propensities of many APP fragments have been studied in vitro, the sequences, structures, and cellular sources of fragments generated in vivo remains poorly elucidated. To better identify the specific APP fragments generated in vivo and to elucidate the role of the proteasome in APP processing, we developed a C99 yeast expression system. Using Zip Tip immunocapture, a specific anti-Abeta antiserum (6E10), and matrix-assisted laser desorption ionization- time of flight mass spectrometry, we identified over one dozen APP-generated peptide fragments in wild-type yeast (PRE1PRE2) and over three dozen unique fragments in proteasome mutant cells (pre1- 1pre2-1) expressing C99. Based on the identities of the immunocaptured species, we propose that defects in proteasome function are compensated by other proteases and that the combination of techniques described here will be invaluable to further delineate the APP processing pathway in vivo. PMID- 17869212 TI - Enzymatic assay of D-serine using D-serine dehydratase from Saccharomyces cerevisiae. AB - D-Serine is localized in the mammalian forebrain and modulates brain functions as a coagonist of an N-methyl-D-aspartate receptor. D-Serine is also found in human urine, although its physiological meaning is unclear. A method for rapid and simple assay of D-serine is probably useful for studying its physiological role and clinical relevance. Currently, D-serine is assayed by high-performance liquid chromatography after derivatization of the amino acid to a diastereomer. The method is time consuming and requires expensive equipment. In this study, we developed a rapid and simple method for the D-serine assay using D-serine dehydratase newly found in Saccharomyces cerevisiae. The yeast d-serine dehydratase acts dominantly on d-serine, in contrast with previously reported bacterial enzymes that act on both D- and L-serine. In our method, pyruvate produced from D-serine by the dehydratase reaction is assayed with lactic dehydrogenase and reduced nicotinamide adenine dinucleotide or with 2,4 dinitrophenylhydrazine. Our enzymatic method could be used for the quantitative determination of D-serine in human urine. PMID- 17869213 TI - Antifibrotic effect via the regulation of transcription factor Sp1 in lung fibrosis. AB - The aim of this study is to evaluate the antifibrotic effect of ring-type Sp1 decoy oligonucleotides (ODNs) through blocking the transcription of transforming growth factor (TGF)-beta1 and its downstream target genes. In this experiment, the expression of TGF-beta1, metalloproteinase (MMP)-13, and fibronectin was decreased in the group with the treatment of the ring-type Sp1 decoy ODNs. Also, alpha-smooth muscle actin positive bronchial lining cells and alveolar epithelial cells were observed, especially around the lesions of extracellular matrix (ECM) deposition. These findings provide evidences for the finding of pulmonary epithelial-mesenchymal transition (EMT) and the effectiveness of Sp1 transcription factor as a target for the gene therapy on lung fibrosis. PMID- 17869214 TI - Novel subsets of the Arabidopsis plasmalemma phosphoproteome identify phosphorylation sites in secondary active transporters. AB - The generation of novel subsets of phosphorylation sites is needed to complement the present Arabidopsis plasma membrane phosphoprotein repertoire, where several families of proteins are under-represented. In this work, different combinations of chromatographic steps were first compared for capacity to resolve model phosphopeptides before characterisation from PSD fragments in MALDI MS/MS. Nearly half of the phosphorylation sites detected in the Arabidopsis plasmalemma using the optimised procedure were novel, and two-thirds of protein accessions identified secondary active transporters. These included phosphate/H(+) symporters, ammonium and nitrate transporters, different alkali cation exchangers, a urea/H(+) symporter, a glucose transporter, a purine permease, and peptide transporters. There has been previous functional evidence for phosphorylation of only a minority of these, the regulation of others having been essentially investigated at the transcriptional level. The demonstration of active phosphorylation sites in such a diverse set of secondary transporter families suggests that this regulation level plays a major role in the response of plants to nutrient availability. PMID- 17869215 TI - Protection from acute cellular injury using Sleeping Beauty mediated telomerase gene transfer. AB - We developed a Sleeping Beauty (SB) transposon mediated hTERT gene delivery system for in vitro use. We have constructed telomerase or luciferase gene expressing SB-transposons with a SV40 enhancer (pT3.hTERT.Con and pT3.Con, respectively) or without an enhancer (pT3.Pro). Using the SB transposon system in vitro hTERT gene overexpression has protective effects from acute cellular injury by tert-butyl hydroperoxide (t-BH), carbon tetrachloride (CCl(4)), and d galactosamine (d-GalN) in normal human cells IMR-90. pT3.hTERT.Con vector and helper plasmid co-transfection resulted in a approximately 3-fold increase in telomerase activity which was maintained for 14 days. Trypan blue and Cell Death Detection Assays showed the protective effects of the telomerase gene against toxic agents. Fourteen days after co-transfection with pT3.hTERT.Con vector and helper plasmid, IMR-90 cells were incubated with 1.2mM t-BH for 50 min, 5mM CCl(4) for 1.5h or 30 mM d-GalN for 24h. Cell viability of SB-mediated telomerase overexpressing cells significantly increased by 48% (t-BH), 43% (CCl(4)), and 25% (d-GalN) in comparison to mock treated cells. Cell Death Detection ELISA showed a decrease in the rate of apoptosis by 47%. In summary, SB transposon mediated telomerase gene transfer may have a protective effect against t-BH, CCl(4), or d GalN induced acute cellular injury, and this results suggested SB-mediated telomerase therapy for tissue engineering. PMID- 17869216 TI - Role of adenosine kinase in the control of Streptomyces differentiations: Loss of adenosine kinase suppresses sporulation and actinorhodin biosynthesis while inducing hyperproduction of undecylprodigiosin in Streptomyces lividans. AB - Adenosine kinase (ADK) catalyses phosphorylation of adenosine (Ado) and generates adenosine monophosphate (AMP). ADK gene (adk(Sli), an ortholog of SCO2158) was disrupted in Streptomyces lividans by single crossover-mediated vector integration. The adk(Sli) disruption mutant (Deltaadk(Sli)) was devoid of sporulation and a plasmid copy of adk(Sli) restored sporulation ability in Deltaadk(Sli), thus indicating that loss of adk(Sli) abolishes sporulation in S. lividans. Ado supplementation strongly suppressed sporulation ability in S. lividans wild-type (wt), supporting that disruption of adk(Sli) resulted in Ado accumulation, which in turn suppressed sporulation. Cell-free experiments demonstrated that Deltaadk(Sli) lacked ADK activity and in vitro characterization confirms that adk(Sli) encodes ADK. The intracellular level of Ado was highly elevated while the AMP level was significantly reduced after loss of adk(Sli) while Deltaadk(Sli) displayed no significant derivation from wt in the levels of S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM). Notably, Ado supplementation to wt lowered AMP content, albeit not to the level of Deltaadk(Sli), implying that the reduction of AMP level is partially forced by Ado accumulation in Deltaadk(Sli). In Deltaadk(Sli), actinorhodin (ACT) production was suppressed and undecylprodigiosin (RED) production was dramatically enhanced; however, Ado supplementation failed to exert this differential control. A promoter-probe assay verified repression of actII-orf4 and induction of redD in Deltaadk(Sli), substantiating that unknown metabolic shift(s) of ADK-deficiency evokes differential genetic control on secondary metabolism in S. lividans. The present study is the first report revealing the suppressive role of Ado in Streptomyces development and the differential regulatory function of ADK activity in Streptomyces secondary metabolism, although the underlying mechanism has yet to be elucidated. PMID- 17869217 TI - Immunomodulation of activated hepatic stellate cells by mesenchymal stem cells. AB - Bone marrow-derived mesenchymal stem cells (MSCs) have been reported to prevent the development of liver fibrosis in a number of pre-clinical studies. Marked changes in liver histopathology and serological markers of liver function have been observed without a clear understanding of the therapeutic mechanism by which stem cells act. We sought to determine if MSCs could modulate the activity of resident liver cells, specifically hepatic stellate cells (SCs) by paracrine mechanisms using indirect cocultures. Indirect coculture of MSCs and activated SCs led to a significant decrease in collagen deposition and proliferation, while inducing apoptosis of activated SCs. The molecular mechanisms underlying the modulation of SC activity by MSCs were examined. IL-6 secretion from activated SCs induced IL-10 secretion from MSCs, suggesting a dynamic response of MSCs to the SCs in the microenvironment. Blockade of MSC-derived IL-10 and TNF-alpha abolished the inhibitory effects of MSCs on SC proliferation and collagen synthesis. In addition, release of HGF by MSCs was responsible for the marked induction of apoptosis in SCs as determined by antibody-neutralization studies. These findings demonstrate that MSCs can modulate the function of activated SCs via paracrine mechanisms provide a plausible explanation for the protective role of MSCs in liver inflammation and fibrosis, which may also be relevant to other models of tissue fibrosis. PMID- 17869218 TI - Protective effect of heat shock protein 27 using protein transduction domain mediated delivery on ischemia/reperfusion heart injury. AB - Heat shock protein 27 (HSP27) is an intracellular stress protein with the cytoprotective effect for a variety of noxious stresses. In this study, using a protein delivery system, we demonstrated the potential cytoprotective effect of HSP27 as a therapeutic protein in cardiac cells and ischemia/reperfusion animal model. We constructed a recombinant HSP27 fused to the protein transduction domain (PTD) derived from HIV-1 TAT protein. Purified recombinant TAT-HSP27 protein was efficiently delivered to H9c2 cells, and its transduction showed cytoprotective effect against the hypoxic stress. Moreover, transduction of TAT HSP27 also attenuated hypoxia-induced apoptosis, which was accompanied by reduced caspase-3 activity. In addition, intraperitoneal injection of TAT-HSP27 into rat resulted in efficient protein transduction in heart tissues, decreased infarcted myocardium (control vs TAT-HSP27, 39.1% vs 29.5%, P<0.05) and preserved heart function (fractional shortening, 15.6% vs 33.4%, P<0.05), as determined at 7 d after I/R. These results suggest that the PTD-mediated delivery of HSP27 protein may represent a potential therapeutic strategy as protein drug for ischemic heart diseases. PMID- 17869219 TI - Human lymphocytes express the transcriptional regulator, Wilms tumor 1: the role of WT1 in mediating nitric oxide-dependent repression of lymphocyte proliferation. AB - The inhibitory roles of nitric oxide (NO) in T cell proliferation have been observed and studied extensively over the last two decades. Despite efforts, the fundamental pathway by which NO exerts its inhibitory actions remains to be elucidated although recent evidence suggests that the transcription factor Wilms tumor 1 (WT1) may be important. WT1 has been linked to numerous developmental pathways in particular nephrogenesis. Due to its roles in development and cell proliferation, polymorphisms within the WT1 gene can result in malignancies such as leukemia and Wilms tumor. WT1 functions as a transcriptional regulator and its activity is controlled through phosphorylation by protein kinase A (PKA). PKA dependent WT1 phosphorylation results in translocation of WT1 from the nucleus to the cytosol, a process that interferes with WT1 transcriptional activities. In the current study we demonstrate that WT1 is expressed in human lymphocytes. Using the proliferative compound PHA we induced T cell proliferation and growth correlated with an increase in the expression of WT1 measured by RT-PCR, flow cytometry and immunoblot. Co-stimulation with the NO donor SNOG at concentrations of 0, 100, 300 and 600 microM reduced in a concentration dependent way the PHA induced upregulation of WT1 that correlated with a reduction in T cell proliferation. We conclude that WT1 might be an important component of the NO dependent regulation of T lymphocyte proliferation and potential function. PMID- 17869220 TI - Unexpected blockade of adipocyte differentiation by K-7174: implication for endoplasmic reticulum stress. AB - Preadipocytes constitutively express GATA-2 and GATA-3 that are required to halt the cells at the undifferentiated stage. However, we unexpectedly found that K 7174, a GATA-specific inhibitor, did not induce but rather inhibited differentiation of 3T3-L1 preadipocytes. It was associated with lack of lipid accumulation, blunted expression of adipocyte markers including adiponectin and peroxisome proliferator-activated receptor gamma (PPARgamma), and sustained expression of a preadipocyte marker monocyte chemoattractant protein 1 (MCP-1). Subsequent experiments revealed that K-7174 had the potential to induce endoplasmic reticulum (ER) stress evidenced by induction of GRP78 and CHOP. Other inducers of ER stress completely reproduced the effects of K-7174 including suppression of lipid accumulation, blockade of induction of adiponection and PPARgamma and maintenance of MCP-1 expression. These results indicated a possibility that ER stress suppresses adipocyte differentiation and that GATA inhibitor K-7174 has the potential for interfering with adipogenesis through induction of ER stress. PMID- 17869221 TI - Analysis of p53-RNA interactions in cultured human cells. AB - Tumor suppressor p53 is a well-characterized transcription factor that binds DNA. More enigmatic are the RNA-binding properties of p53 and their physiological relevance. We used three sensitive co-immunoprecipitation methods in an attempt to detect RNAs that tightly associate with p53 in cultured human cells. Although recombinant p53 protein binds RNA in a sequence-nonspecific mode, we do not detect specific in vivo RNA binding by p53. These results suggest that RNA binding is prevented by post-translational p53 modifications. A ribonucleoprotein (not p53) is purified by multiple IgG monoclonal antibodies (including anti-p53 antibodies) from both p53 +/+ and p53 null cells. Caution is therefore required in interpreting RNA co-immunoprecipitation experiments. Though not formally excluded, these results do not support models in which p53 binds specific RNA partners in vivo. PMID- 17869222 TI - The effect of dendritic cells on the retinal cell transplantation. AB - The potential of bone marrow cell-derived immature dendritic cells (myeloid iDCs) in modulating the efficacy of retinal cell transplantation therapy was investigated. (1) In vitro, myeloid iDCs but not BMCs enhanced the survival and proliferation of embryonic retinal cells, and the expression of various neurotrophic factors by myeloid iDCs was confirmed with RT-PCR. (2) In subretinal transplantation, neonatal retinal cells co-transplanted with myeloid iDCs showed higher survival rate compared to those transplanted without myeloid iDCs. (3) CD8 T-cells reactive against donor retinal cells were significantly increased in the mice with transplantation of retinal cells alone. These results suggested the beneficial effects of the use of myeloid iDCs in retinal cell transplantation therapy. PMID- 17869223 TI - Trichostatin-A induces differential changes in histone protein dynamics and expression in HeLa cells. AB - Trichostatin-A (TSA), a histone deacetylase (HDAC) inhibitor, results in enhanced acetylation of core histones thereby disrupting chromatin organization within living cells. We report on changes in chromatin organization and the resultant alteration in nuclear architecture following treatment with TSA using fluorescence imaging. TSA triggers an expected increase in the euchromatin fraction which is accompanied by a significant increase in nuclear volume and alterations in chromatin compaction mapped using fluorescence anisotropy imaging. We observe differential changes in the mobility of core and linker histones as measured by fluorescence recovery after photo-bleaching (FRAP) and fluorescence correlation spectroscopy (FCS) methods. Further TSA induces a differential increase in linker histone transcription and increased phosphorylation of linker histone proteins accompanying an expected increase in core histone acetylation patterns. Thus subtle feedback responses triggered by changes in chromatin configurations impinge selectively on linker histone mobility and its expression. These observations have implications for understanding the role of HDAC in the dynamic maintenance of chromatin organization. PMID- 17869224 TI - A1 receptor deficiency causes increased insulin and glucagon secretion in mice. AB - Adenosine influences metabolism and the adenosine receptor antagonist caffeine decreases the risk of type 2 diabetes. In this study the metabolic role of one adenosine receptor subtype, the adenosine A(1)R, was evaluated in mice lacking this receptor [A(1)R (-/-)]. The HbA1c levels and body weight were not significantly different between wild type [A(1)R (+/+)] and A(1)R (-/-) mice (3-4 months) fed normal lab chow. At rest, plasma levels of glucose, insulin and glucagon were similar in both genotypes. Following glucose injection, glucose tolerance was not appreciably altered in A(1)R (-/-) mice. Glucose injection induced sustained increases in plasma insulin and glucagon levels in A(1)R (-/-) mice, whereas A(1)R (+/+) control mice reacted with the expected transient increase in insulin and decrease in glucagon levels. Pancreas perfusion experiments showed that A(1)R (-/-) mice had a slightly higher basal insulin secretion than A(1)R (+/+) mice. The first phase insulin secretion (initiated with 16.7 mM glucose) was of the same magnitude in both genotypes, but the second phase was significantly enhanced in the A(1)R (-/-) pancreata compared with A(1)R (+/+). Insulin- and contraction-mediated glucose uptake in skeletal muscle were not significantly different between in A(1)R (-/-) and A(1)R (+/+) mice. All adenosine receptors were expressed at mRNA level in skeletal muscle in A(1)R (+/+) mice and the mRNA A(2A)R, A(2B)R and A(3)R levels were similar in A(1)R (-/ ) and A(1)R (+/+) mice. In conclusion, the A(1)R minimally affects muscle glucose uptake, but is important in regulating pancreatic islet function. PMID- 17869225 TI - Cyanidin 3-glucoside ameliorates hyperglycemia and insulin sensitivity due to downregulation of retinol binding protein 4 expression in diabetic mice. AB - Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine expression is one of the most important targets for the prevention of obesity and improvement of insulin sensitivity. In this study, we have demonstrated that anthocyanin (cyanidin 3-glucoside; C3G) which is a pigment widespread in the plant kingdom, ameliorates hyperglycemia and insulin sensitivity due to the reduction of retinol binding protein 4 (RBP4) expression in type 2 diabetic mice. KK-A(y) mice were fed control or control +0.2% of a C3G diet for 5 weeks. Dietary C3G significantly reduced blood glucose concentration and enhanced insulin sensitivity. The adiponectin and its receptors expression were not responsible for this amelioration. C3G significantly upregulated the glucose transporter 4 (Glut4) and downregulated RBP4 in the white adipose tissue, which is accompanied by downregulation of the inflammatory adipocytokines (monocyte chemoattractant protein-1 and tumor necrosis factor-alpha) in the white adipose tissue of the C3G group. These findings indicate that C3G has significant potency in an anti diabetic effect through the regulation of Glut4-RBP4 system and the related inflammatory adipocytokines. PMID- 17869226 TI - Anti-tumor potential of 15,16-dihydrotanshinone I against breast adenocarcinoma through inducing G1 arrest and apoptosis. AB - Chemotherapeutic drugs are usually designed to induce cancer cell death via cell cycle arrest and/or apoptosis pathways. In this study, we used the chemical drug 15,16-dihydrotanshinone I (DHTS) to inhibit breast cancer cell proliferation and tumor growth, and investigate the underlying molecular mechanisms. Human breast cancer cell lines MCF-7 and MDA-MB-231 were both used in this study, and DHTS was found to significantly decrease cell proliferation by a dose-dependent manner in both cells. Flow cytometry indicated that DHTS induced G1 phase arrest in synchronous MCF-7 and MDA-MB-231 cells. When analyzing the expression of cell cycle-related proteins, we found that DHTS reduced cyclin D1, cyclin D3, cyclin E, and CDK4 expression, and increased CDK inhibitor p27 expression in a dose dependent manner. In addition, DHTS inhibited the kinase activities of CDK2 and CDK4 by an immunocomplex kinase assay. In addition, DHTS also induced apoptosis in both cells through mainly mitochondrial apoptosis pathways. We found that DHTS decreased the anti-apoptotic protein Bcl-xL level and increased the loss of mitochondria membrane potential and the amount of cytochrome c released. Moreover, DHTS activated caspase-9, caspase-3, and caspase-7 and caused cell apoptosis. The fact that DHTS-induced apoptosis could be blocked by pretreating cells with pan-caspase inhibitor confirmed that it is mediated through activation of the caspase-3-dependent pathway. In a nude mice xenograft experiment, DHTS significantly inhibited the tumor growth of MDA-MB-231 cells. Taken together, these results suggest that DHTS can inhibit human breast cancer cell proliferation and tumor growth, and might have potential chemotherapeutic applications. PMID- 17869227 TI - The involvement of AMP-activated protein kinases in the anti-inflammatory effect of nicotine in vivo and in vitro. AB - AMP-activated protein kinase (AMPK) is the downstream component of a kinase cascade that plays a pivotal role in energy homeostasis. AMPK has recently emerged as an attractive and novel target for inflammatory disorders. Thus, the aim of this study was to assess the role of AMPKalpha in the anti-inflammatory effect of nicotine in carrageenan-induced rat paw edema model and to evaluate the mechanism of nicotine-induced AMPKalpha phosphorylation in RAW 264.7 cells. The results indicate that nicotine alleviated paw edema and the activation of AMPKalpha involved in the anti-inflammatory effect of nicotine in vivo. In addition, nicotine was able to activate AMPKalpha phosphorylation in macrophages and this effect was mediated through nicotinic acetylcholine receptors. Furthermore, nicotine significantly induced the phosphorylation of Akt and the Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK) protein expression in macrophages. Wortmannin, a specific inhibitor of phosphotidylinositol 3-kinase (PI3K), suppressed nicotine-induced Akt and AMPKalpha phosphorylation. STO-609, a CaMKK inhibitor, not only inhibited the activation of AMPKalpha but also suppressed the phosphorylation of Akt induced by nicotine. In conclusion, both of CaMKK and PI3K/Akt pathways are involved in the nicotine-induced AMPKalpha phosphorylation in macrophages, and the interaction of CaMKK and Akt may exist. AMPKalpha is a novel and critical component of anti-inflammatory effect of nicotine. PMID- 17869228 TI - Neurochemical organization of the nucleus paramedianus dorsalis in the human. AB - We have characterized the neurochemical organization of a small brainstem nucleus in the human brain, the nucleus paramedianus dorsalis (PMD). PMD is located adjacent and medial to the nucleus prepositus hypoglossi (PH) in the dorsal medulla and is distinguished by the pattern of immunoreactivity of cells and fibers to several markers including calcium-binding proteins, a synthetic enzyme for nitric oxide (neuronal nitric oxide synthase, nNOS) and a nonphosphorylated neurofilament protein (antibody SMI-32). In transverse sections, PMD is oval with its long axis aligned with the dorsal border of the brainstem. We identified PMD in eight human brainstems, but found some variability both in its cross-sectional area and in its A-P extent among cases. It includes calretinin immunoreactive large cells with oval or polygonal cell bodies. Cells in PMD are not immunoreactive for either calbindin or parvalbumin, but a few fibers immunoreactive to each protein are found within its central region. Cells in PMD are also immunoreactive to nNOS, and immunoreactivity to a neurofilament protein shows many labeled cells and fibers. No similar region is identified in atlases of the cat, mouse, rat or monkey brain, nor does immunoreactivity to any of the markers that delineate it in the human reveal a comparable region in those species. The territory that PMD occupies is included in PH in other species. Since anatomical and physiological data in animals suggest that PH may have multiple subregions, we suggest that the PMD in human may be a further differentiation of PH and may have functions related to the vestibular control of eye movements. PMID- 17869230 TI - Hyperbaric oxygen therapy improves spatial learning and memory in a rat model of chronic traumatic brain injury. AB - In the present experiment we use a rat model of traumatic brain injury to evaluate the ability of low-pressure hyperbaric oxygen therapy (HBOT) to improve behavioral and neurobiological outcomes. The study employed an adaptation of the focal cortical contusion model. 64 Male Long-Evans rats received unilateral cortical contusion and were tested in the Morris Water Task (MWT) 31-33 days post injury. Rats were divided into three groups: an untreated control group (N=22), an HBOT treatment group (N=19) and a sham-treated normobaric air group (N=23). The HBOT group received 80 bid, 7 days/week 1.5 ATA/90-min HBOTs and the sham treated normobaric air group the identical schedule of air treatments using a sham hyperbaric pressurization. All rats were subsequently retested in the MWT. After testing all rats were euthanized. Blood vessel density was measured bilaterally in hippocampus using a diaminobenzadine stain and was correlated with MWT performance. HBOT caused an increase in vascular density in the injured hippocampus (p<0.001) and an associated improvement in spatial learning (p<0.001) compared to the control groups. The increased vascular density and improved MWT in the HBOT group were highly correlated (p<0.001). In conclusion, a 40-day series of 80 low-pressure HBOTs caused an increase in contused hippocampus vascular density and an associated improvement in cognitive function. These findings reaffirm the clinical experience of HBOT-treated patients with chronic traumatic brain injury. PMID- 17869229 TI - Time-dependent effect of epidural steroid on pain behavior induced by chronic compression of dorsal root ganglion in rats. AB - Although epidural steroid injection has been commonly used to treat radicular pain, its clinical efficacy remains controversial. In a rat model of radicular pain induced by chronic compression of lumbar dorsal root ganglion (CCD), we examined the effect of epidural steroid on CCD-induced pain behavior. Triamcinolone [a glucocorticoid receptor (GR) agonist] or RU38486 (a GR antagonist) was given epidurally once either on day 3 (early treatment) or day 10 (late treatment) after CCD. The results showed that 1) early treatment with triamcinolone and RU38486 alone, respectively, reduced and exacerbated mechanical allodynia and thermal hyperalgesia, 2) late treatment with triamcinolone alone failed to improve mechanical allodynia and only transiently attenuated thermal hyperalgesia, and 3) late treatment with RU38486 alone improved mechanical allodynia and thermal hyperalgesia in CCD rats. Moreover, a second dose of triamcinolone given on day 10 paradoxically exacerbated pain behavior in CCD rats that received a first dose of triamcinolone on day 3. These results indicate that the effect of epidural steroid on radicular pain may be time-dependent. Clinical implications for epidural steroid treatment are discussed in light of these preclinical findings. PMID- 17869231 TI - Inhibition of SR Ca2+ uptake: a novel action of the RyR2-FKBP12.6 antagonist K201. PMID- 17869232 TI - Drug-induced torsades de pointes--a form of mechano-electric feedback? PMID- 17869233 TI - Plasma chitotriosidase in lysosomal storage diseases. PMID- 17869234 TI - Cost-effectiveness analysis in diagnosis of coronary artery disease: choice of laboratory markers. AB - OBJECTIVES: The aim of our study was to determine the cost-effectiveness of coronary artery disease (CAD) diagnostic parameters in a clinical laboratory setting. DESIGN AND METHODS: The effectiveness of apolipoproteins, lipoproteins and high sensitivity C-reactive protein (hs-CRP) supplementary to Framingham scoring data within a CAD risk assessment procedure was established in 221 CAD patients and 289 controls. The total costs of diagnostic procedures were calculated and incremental cost-effectiveness analysis was applied. RESULTS: A diagnostic strategy employing Framingham calculation followed by apolipoprotein A I (apoA-I) had the lowest cost per additional successfully diagnosed patient than the same strategy followed by hs-CRP in the low (2.63 vs. 24.47 euros) and intermediate-risk groups (2.96 vs. 122.85 euros). In the high-risk group the diagnostic strategy employing apoA-I saved 9.14 euros in comparison to the strategy employing hs-CRP. CONCLUSION: Cost-effectiveness analysis of different diagnostic markers results in improved identification of at-risk patients at a lower health cost for society. PMID- 17869235 TI - Goal attribution to inanimate agents by 6.5-month-old infants. AB - Human infants' tendency to attribute goals to observed actions may help us to understand where people's obsession with goals originates from. While one-year old infants liberally interpret the behaviour of many kinds of agents as goal directed, a recent report [Kamewari, K., Kato, M., Kanda, T., Ishiguro, H., & Hiraki, K. (2005). Six-and-a-half-month-old children positively attribute goals to human action and to humanoid-robot motion. Cognitive Development, 20, 303-320] suggested that younger infants restrict goal attribution to humans and human-like creatures. The present experiment tested whether 6.5-month-old infants would be willing to attribute a goal to a moving inanimate box if it slightly varied its goal approach within the range of the available efficient actions. The results were positive, demonstrating that featural identification of agents is not a necessary precondition of goal attribution in young infants and that the single most important behavioural cue for identifying a goal-directed agent is variability of behaviour. This result supports the view that the bias to give teleological interpretation to actions is not entirely derived from infants' experience. PMID- 17869236 TI - Induction of multiple criteria optimal classification rules for biological and medical data. AB - To induce critical classification rules from observed data is a major task in biological and medical research. A classification rule is considered to be useful if it is optimal and simultaneously satisfies three criteria: is highly accurate, has a high rate of support, and is highly compact. However, current classification methods, such as rough set theory, neural networks, ID3, etc., may only induce feasible rules instead of optimal rules. In addition, the rules found by current methods may only satisfy one of the three criteria. This study proposes a multi-criteria model to induce optimal classification rules with better rates of accuracy, support and compactness. A linear multi-objective programming model for inducing classification rules is formulated. Two practical data sets, one of HSV patients results and another of European barn swallows, are tested. The results illustrate that the proposed method can induce better rules than current methods. PMID- 17869237 TI - Essential role of Smad4 in maintaining cardiomyocyte proliferation during murine embryonic heart development. AB - Transforming growth factor-beta/bone morphogenetic protein (TGF-beta/BMP) signaling pathway is essential for embryonic and postnatal heart development and remodeling. The intracellular factor Smad4 plays a pivotal role in mediating TGF beta/BMP signal transduction in the nucleus. To examine the function of Smad4 in embryonic cardiac development during mid-gestation, we specifically deleted the Smad4 gene in embryonic cardiomyocytes using the Cre-LoxP system. Deletion of Smad4 as early as E9.5, led to embryonic lethality between E12.5 and E15.5, and embryos exhibited severe morphological defects in the heart, including a thin compact layer, disorganized trabeculae, and ventricular septum defects (VSD). Smad4 deletion also led to a dramatic decrease in cardiomyocyte proliferation accompanied by downregulation of contractile protein-encoding genes such as alpha myosin heavy chain, beta-myosin heavy chain, ventricular myosin light chain 2, and alpha-cardiac actin. In addition, deletion of Smad4 resulted in perturbation of TGF-beta/BMP ligand expression and signaling, and defects in expression of several cardiac transcription factor genes such as Nkx2.5, GATA4, and MEF2c. These results provide direct genetic evidences that Smad4 is essential for regulating cardiomyocyte proliferation and differentiation during murine cardiogenesis, and provides new insights into potential causes of congenital heart disease. PMID- 17869238 TI - crm-1 facilitates BMP signaling to control body size in Caenorhabditis elegans. AB - We have identified in Caenorhabditis elegans a homologue of the vertebrate Crim1, crm-1, which encodes a putative transmembrane protein with multiple cysteine-rich (CR) domains known to have bone morphogenetic proteins (BMPs) binding activity. Using the body morphology of C. elegans as an indicator, we showed that attenuation of crm-1 activity leads to a small body phenotype reminiscent of that of BMP pathway mutants. We showed that the crm-1 loss-of-function phenotype can be rescued by constitutive supply of sma-4 activity. crm-1 can enhance BMP signaling and this activity is dependent on the presence of the DBL-1 ligand and its receptors. crm-1 is expressed in neurons at the ventral nerve cord, where the DBL-1 ligand is produced. However, ectopic expression experiments reveal that crm 1 gene products act outside the DBL-1 producing cells and function non autonomously to facilitate dbl/sma pathway signaling to control body size. PMID- 17869240 TI - Redundancy and evolution of GATA factor requirements in development of the myocardium. AB - The transcription factors, GATA4, 5 and 6, recognize the same DNA sequence and are all expressed in the developing myocardium. However, knockout studies in the mouse have indicated that none of them are absolutely required for the specification of the myocardium. Here we present evidence for redundancy in this family for the first time. Using morpholinos in both Xenopus and zebrafish embryos, we show that GATA4 knockdown, for example, only affects cardiac marker expression in the absence of either GATA5 or GATA6. A similar situation pertains for GATA5 in Xenopus whereas, in zebrafish, GATA5 (faust) plays a major role in driving the myocardial programme. This requirement for GATA5 in zebrafish is for induction of the myocardium, in contrast to the GATA6 requirement in both species, which is for differentiation. This early role for GATA5 in zebrafish correlates with its earlier expression and with an earlier requirement for BMP signalling, suggesting that a mutual maintenance loop for GATA, BMP and Nkx expression is the evolutionarily conserved entity. PMID- 17869239 TI - The GATA factor Serpent cross-regulates lozenge and u-shaped expression during Drosophila blood cell development. AB - The Drosophila GATA factor Serpent interacts with the RUNX factor Lozenge to activate the crystal cell program, whereas SerpentNC binds the Friend of GATA protein U-shaped to limit crystal cell production. Here, we identified a lozenge minimal hematopoietic cis-regulatory module and showed that lozenge-lacZ reporter gene expression was autoregulated by Serpent and Lozenge. We also showed that upregulation of u-shaped was delayed until after lozenge activation, consistent with our previous results that showed u-shaped expression in the crystal cell lineage is dependent on both Serpent and Lozenge. Together, these observations describe a feed forward regulatory motif, which controls the temporal expression of u-shaped. Finally, we showed that lozenge reporter-gene activity increased in a u-shaped mutant background and that forced expression of SerpentNC with U shaped blocked lozenge- and u-shaped-lacZ reporter-gene activity. This is the first demonstration of GATA:FOG regulation of Runx and Fog gene expression. Moreover, these results identify components of a Serpent cross-regulatory sub circuit that can modulate lozenge expression. Based on the sub-circuit design and the combinatorial control of crystal cell production, we present a model for the specification of a dynamic bi-potential regulatory state that contributes to the selection between a Lozenge-positive and Lozenge-negative state. PMID- 17869241 TI - Lack of development of behavioral sensitization to methylphenidate in mice: correlation with reversible astrocytic activation. AB - Methamphetamine is a powerfully addictive psychostimulant that dramatically affects the mammalian central nervous system. Methylphenidate has been shown to have psychostimulus effects similar to methamphetamine. In the present study, we compared several effects of methylphenidate to those of methamphetamine. The subcutaneous administration of either methamphetamine or methylphenidate increased extracellular dopamine levels in the nucleus accumbens of mice. Interestingly, methamphetamine, but not methylphenidate, also increased the extracellular serotonin levels in this area. Further, repeated treatment with methamphetamine induced the development of sensitization to hyperlocomotion, whereas methylphenidate failed to induce behavioral sensitization. Moreover, in vitro treatment with methamphetamine, but not methylphenidate, caused long lasting astrocytic activation in limbic neuron/glia co-cultures. These findings suggest that, unlike methamphetamine, methylphenidate shows a lack of development of behavioral sensitization to its hyperlocomotion and induces reversible astrocytic activation. PMID- 17869242 TI - Enantio-selective effects of clenbuterol in cultured neurons and astrocytes, and in a mouse model of cerebral ischemia. AB - Neuroprotective effects of the lipophilic beta(2)-adrenoceptor agonist clenbuterol have been established in neuronal cultures and in various rodent models of stroke. In previous studies, however, clenbuterol was always applied as a racemate, while it has not been established whether the enantiomers differ in their neuroprotective activities. Here, we demonstrate that R,S-clenbuterol and S(+)-clenbuterol, but not the R(-)-enantiomer protect cultured neurons against glutamate-mediated excitotoxicity and staurosporine-induced apoptosis. Similar to previous findings with clenbuterol racemate, the neuroprotective effect of S(+) clenbuterol correlated well with morphological changes of astrocytes which transformed into dense stellate cells with dendritic processes indicating beta(2) adrenoceptor-mediated activation. Most importantly, the S(+)-enantiomer but not R(-)-clenbuterol reduced ischemic brain damage similar to the effect of the racemate. The selective beta(2)-adrenoceptor antagonist butoxamine blocked this neuroprotective effect of S(+)-clenbuterol. In addition, S(+)-clenbuterol significantly reduced blood pressure, enhanced blood glucose levels and increased glucocorticoid levels compared to vehicle-or R(-)-clenbuterol-treated controls. These results clearly demonstrate that S(+)-clenbuterol is the eutomer that mediates neuroprotective effects of the beta(2)-adrenoceptor agonist but also according changes of physiological parameters. PMID- 17869243 TI - Differential desensitization of dopamine D2 receptor isoforms by protein kinase C: the importance of receptor phosphorylation and pseudosubstrate sites. AB - Altered regulation of dopamine D(2) receptors is implicated in addiction, schizophrenia and movement disorders, as well as lactotroph growth and regulation. Dopamine D(2S) and dopamine D(2L) receptors are alternately-spliced variants that differ by 29 amino acids in the third intracellular (i3) domain and display different sensitivity to desensitization by protein kinase C (PKC). In the present studies we determined the specific phosphorylation sites on the dopamine D(2S) receptor that confer PKC-mediated desensitization. In dopamine D(2L) receptors, we identified a PKC pseudosubstrate site responsible for the relative insensitivity of the receptor to PKC-induced uncoupling. In transiently transfected Ltk(-) fibroblast cells, 2-min preactivation of PKC with 12-O tetradecanoyl 4beta-phorbol 13alpha-acetate (TPA) completely inhibited calcium mobilization induced by the dopamine D(2S) receptor, but not the dopamine D(2L) variant. Point mutation of i3 PKC sites Ser228/229Gly rendered the dopamine D(2S) receptor resistant to PKC action, with lesser effects of other Ser and Thr mutations. Inactivation of the PKC pseudosubstrate motif in the dopamine D(2L) receptor sensitized the receptor to PKC, and this was reversed by mutation of i3 PKC sites Ser228/229. A phospho-specific antibody generated against phospho Ser228/229 demonstrated PKC-induced phosphorylation at these sites of dopamine D(2S), but not D(2L) receptors, in Ltk(-) cells. Conversely, the pseudosubstrate dopamine D(2L) receptor mutant displayed PKC-induced phosphorylation at Ser228/229, which was abolished when these sites were mutated. Similar phosphorylation results were observed using GH4 cells stably transfected with dopamine D(2) receptors and mutants. Thus the relative location of phosphorylation and pseudosubstrate sites provides an important determinant substrate sensitivity to PKC. PMID- 17869244 TI - CRM1-dependent nuclear export and dimerization with hMSH5 contribute to the regulation of hMSH4 subcellular localization. AB - MSH4 and MSH5 are members of the MutS homolog family, a conserved group of proteins involved in DNA mismatch correction and homologous recombination. Although several studies have provided compelling evidences suggesting that MSH4 and MSH5 could act together in early and late stages of meiotic recombination, their precise roles are poorly understood and recent findings suggest that the human MSH4 protein may also exert a cytoplasmic function. Here we show that MSH4 is present in the cytoplasm and the nucleus of both testicular cells and transfected somatic cells. Confocal studies on transfected cells provide the first evidence that the subcellular localization of MSH4 is regulated, at least in part, by an active nuclear export pathway dependent on the exportin CRM1. We used deletion mapping and mutagenesis to define two functional nuclear export sequences within the C-terminal part of hMSH4 that mediate nuclear export through the CRM1 pathway. Our results suggest that CRM1 is also involved in MSH5 nuclear export. In addition, we demonstrate that dimerization of MSH4 and MSH5 facilitates their nuclear localization suggesting that dimerization may regulate the intracellular trafficking of these proteins. Our findings suggest that nucleocytoplasmic traffic may constitute a regulatory mechanism for MSH4 and MSH5 functions. PMID- 17869246 TI - JAK/STAT pathway mediates retinal ganglion cell survival after acute ocular hypertension but not under normal conditions. AB - Intraocular pressure (IOP) elevation is an important cause of glaucoma. Animal models of ocular hypertension have been widely used to mimic glaucoma to investigate the mechanisms underlying retinal ganglion cell (RGC) death and search for possible cure. The aim of the present study was to examine the role of JAK/STAT pathway in RGC viability in normal condition or after acute IOP elevation. Retinal explants obtained from intact or IOP-elevated eyes were firstly used to examine the effect of the JAK/STAT pathway inhibitors, AG490 and Jak Inhibitor I, on RGC viability in vitro. The role of this signal pathway was further investigated and confirmed in vivo. AG490 and Jak Inhibitor I were applied into the left eye on days 3, 9, and 15 post 2-h IOP elevation at 110mmHg. Fluorescence dye Fluorogold was used to retrogradely label surviving RGCs. Because macrophage recruitment was seen in the IOP-elevated eyes after inhibition of this pathway, clodronate liposomes were used to remove phagocytic cells in the eye and examine the role of JAK/STAT pathway in RGC survival independent of macrophages. Activities and location of JAK/STAT pathway in the retina were examined using Western blotting and immunohistochemistry. We found that inhibition of JAK/STAT pathway did not affect RGC survival in the retinal explants derived from intact eye but caused RGC death in the retinal explants that were derived from IOP-elevated eye. Importantly, the detrimental effect of JAK/STAT pathway inhibition on RGC survival was also observed in vivo following acute IOP elevation, but not in intact eye. In addition, both in vitro and in vivo experiments confirmed a detrimental action of phagocytic cells following acute IOP elevation and the pathway inhibition. Compatible with what were observed in vivo, Western blotting and immunohistochemistry showed that JAK/STAT activities were not present in intact retina, but acute IOP elevation activated JAK/STAT pathway in the retina, in the regions of inner nuclear layer and ganglion cell layer, including RGCs. The IOP elevation-induced JAK/STAT activities were effectively abolished by intravitreal application of AG490. This study thus shows that (1) acute IOP elevation activates JAK/STAT pathway in RGCs, and (2) JAK/STAT pathway mediates RGC survival following IOP elevation but not under normal condition. PMID- 17869245 TI - Dynamic protrusive cell behaviour generates force and drives early matrix contraction by fibroblasts. AB - We investigated the cellular mechanisms underlying force generation and matrix contraction, using human corneal, Tenon's and scleral fibroblasts in a standard collagen matrix. We used timelapse light and confocal reflection microscopy to analyse concomitantly cell behaviour and matrix remodeling during contraction and devised a novel index to quantify dynamic cell behaviour in 3D. Based on the previously described culture force monitor, a novel simultaneous imaging and micro-culture force monitor system (SIM-CFM) was developed to measure the mechanical strain generated during matrix contraction whilst simultaneously recording cell and matrix behaviour. Ocular fibroblasts show marked differences in macroscopic matrix contraction profiles, with corneal fibroblasts inducing the strongest, and scleral the weakest, contraction. We identified four factors that determine the early matrix contraction profile: 1) cell size, 2) intrinsic cellular force, 3) dynamic cell protrusive activity and 4) net pericellular matrix displacement. Intrinsic cellular force and dynamic activity appear to be independent unique characteristics of each cell type and might serve as predictors of matrix contraction. The identification of these factors raises the fundamental new possibilities of predicting the ability of tissues to contract and scar and of modulating tissue contraction by targeting intracellular pathways linked to protrusive activity and force generation. PMID- 17869247 TI - Mover is a novel vertebrate-specific presynaptic protein with differential distribution at subsets of CNS synapses. AB - Presynaptic nerve terminals contain scaffolding proteins that orchestrate neurotransmitter release at active zones. Here we describe mover, a yet unknown non-transmembrane protein that is targeted to presynaptic terminals when overexpressed in cultured neurons. Confocal immunomicroscopy revealed that mover colocalizes with presynaptic markers in the calyx of Held. In the hippocampus, mover localizes to mossy fibre terminals, but is absent from inhibitory nerve terminals. By contrast, mover localizes to inhibitory terminals throughout the cerebellar cortex. Our results suggest that mover may act in concert with generally expressed scaffolding proteins in distinct sets of presynaptic terminals. PMID- 17869248 TI - Extensive mutagenesis experiments corroborate a structural model for the DNA deaminase domain of APOBEC3G. AB - APOBEC3G is a single-strand DNA cytosine deaminase capable of blocking retrovirus and retrotransposon replication. APOBEC3G has two conserved zinc-coordinating motifs but only one is required for catalysis. Here, deletion analyses revealed that the minimal catalytic domain consists of residues 198-384. Size exclusion assays indicated that this protein is monomeric. Many (31/69) alanine substitution derivatives of APOBEC3G198-384 retained significant to full levels of activity. These data corroborated an APOBEC2-based structural model for the catalytic domain of APOBEC3G indicating that most non-essential residues are solvent accessible and most essential residues cluster within the protein core. PMID- 17869249 TI - The PPARdelta agonist, GW501516, promotes fatty acid oxidation but has no direct effect on glucose utilisation or insulin sensitivity in rat L6 skeletal muscle cells. AB - Peroxisome proliferator-activated receptor-delta (PPARdelta) activation enhances skeletal muscle fatty acid oxidation and improves whole body glucose homeostasis and insulin sensitivity. Recently, GW501516, a selective PPARdelta agonist, was reported to increase glucose uptake in human skeletal myotubes by an AMPK dependent mechanism that may contribute to the improved glucose tolerance. Here, we demonstrate that whilst GW501516 increases expression of PGC-1alpha and CPT-1 and stimulates fatty-acid oxidation in L6 myotubes, it fails to enhance insulin sensitivity, AMPK activity or glucose uptake and storage. Our findings exclude sarcolemmal glucose transport as a potential target for the therapeutic action of PPARdelta agonists in skeletal muscle. PMID- 17869250 TI - Catalytic domain of MMP20 (Enamelysin) - the NMR structure of a new matrix metalloproteinase. AB - The solution structure of the catalytic domain of MMP-20, a member of the matrix metalloproteinases family not yet structurally characterized, complexed with N Isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid (NNGH), is here reported and compared with other MMPs-NNGH adducts. The backbone dynamic has been characterized as well. We have found that, despite the same fold and very high overall similarity, the present structure experiences specific structural and dynamical similarities with some MMPs and differences with others, around the catalytic cavity. The present solution structure, not only contributes to fill the gap of structural knowledge on human MMPs, but also provides further information to design more selective and efficient inhibitors for a specific member of this class of proteins. PMID- 17869251 TI - Diurnal patterns and sex differences in cortisol, 11-ketotestosterone, testosterone, and 17beta-estradiol in the bluebanded goby (Lythrypnus dalli). AB - The primary goals of this study were to evaluate diurnal patterns of and sex differences in the levels of cortisol, 11-ketotestosterone, testosterone, and 17beta-estradiol in the sex-changing bluebanded goby Lythrypnus dalli. Steroid hormones were collected from water samples and analyzed by enzyme immunoassay. During the breeding season, hormones were sampled from both males and females at seven time points between 0600 and 2000 h. When comparing each time point separately, there were significant overall time effects for cortisol and 17beta estradiol. Cortisol concentrations were lowest at the 0800-1000 h sampling point and showed a qualitative peak in late morning (1000-1200 h). Concentrations of 17beta-estradiol were elevated at the last sampling point (1800-2000 h). Broader temporal trends were revealed for testosterone and 11-ketotestosterone concentrations, both of which were elevated in the morning. There were no sex differences in overall hormone concentrations or temporal profiles for cortisol, 11-ketotestosterone, or testosterone. Males and females showed similar diurnal patterns of 17beta-estradiol but females had significantly higher water-borne 17beta-estradiol levels than males. The results show the presence of diurnal changes in steroid hormone levels in male and female bluebanded gobies. The lack of sex differences in androgens suggests that males of this species, and perhaps other bi-directional sex-changing species in which males do not exhibit prominent secondary sexual characteristics, do not require persistent elevations in 11 ketotestosterone or testosterone to maintain the male phenotype. Although the role of 17beta-estradiol in maintaining sex differences in sexually plastic species is unclear, our results suggest that, of the hormones measured, 17beta estradiol has the greatest potential for future studies interested in this question. PMID- 17869252 TI - The classification of obstetric vesico-vaginal fistulas: a call for an evidence based approach. AB - Classification systems for vesico-vaginal fistulas (VVFs) are as old as fistula surgery itself. Many classification systems have been proposed over the past 150 years, and nearly all have been based on descriptions of the size and anatomic location of the defect. While useful in communicating the appearance of a given fistula, systems based on size and anatomy do not necessarily give information on the difficulty of repair or the prognosis for successful outcome. This article serves as a call for a classification system for VVFs based on outcome rather than anatomy. Developing a reliable system will require data resources that do not yet exist. Based on incomplete data from a Nigerian VVF center, a possible system is proposed for further study. Once available, an outcome-based classification system could be vital in selecting fistula cases appropriate for training surgeons, and in improving communication with patients. PMID- 17869253 TI - USAID program for the prevention and treatment of vaginal fistula. AB - The cornerstone of the US Agency for International Development (USAID) fistula program is to support and strengthen local capacity for fistula repair. The USAID program includes support to upgrade facilities, enhance local surgical repair capability, allocate equipment and supplies to operating rooms, implement quality improvement systems, and cover the women's transportation costs to and from the treatment facilities. The program also offers training in clinical and counseling skills; transferring skills South-to-South; and monitoring and evaluating the program's effectiveness. As new fistula cases continually increase the backlog of untreated cases, its efforts are also directed toward the prevention of fistula and the reintegration of treated women into their communities. Furthermore, the program challenges the culture of sexual violence against women that leads to traumatic gynecologic fistulas. PMID- 17869254 TI - Obstetric fistula admissions at Komfo Anokye Teaching Hospital, Kumasi, Ghana. PMID- 17869255 TI - Improving community knowledge of obstetric fistula prevention and treatment. AB - In recent years, information has emerged in the scientific literature regarding the experience of physicians and clinical staff who try to prevent and treat obstetric fistulas at health facilities in developing countries. However, little is known about attempts to match the services they provide with policy and programmatic interventions in the communities they serve. To determine what is known about community involvement in the prevention and treatment of obstetric fistulas, the authors inquired into experiments carried out by EngenderHealth and partners in 15 African and Asian countries. From raw data, gray literature, and personal communications with those working in the field, they learned that engaging the community may be the keystone in the eradication of fistulas in low resource settings, and they learned how to engage the community. PMID- 17869256 TI - Urogenital and recto-vaginal fistulas in southern Malawi: a report on 407 patients. AB - This study from Southern Malawi reports on 407 patients with 408 vaginal fistulas (1 patient had 2 successive fistulas). There were 29 patients (7.6%) with a combined urogenital and recto-vaginal fistula. Obstructed labor was the cause of 379 fistulas and the remaining 29 were not of obstetric origin. Although the actual incidence of vaginal fistulas is unknown, the incidence is probably much lower in Malawi than in other African countries. The rate of closure at first repair was 94.1% for urogenital fistulas but it reached 98.5% overall. For recto vaginal fistulas, closure at first repair was 78.8% but the overall rate of successful closure was 87.9%. Stress incontinence was seen in 16.2% of the patients immediately after repair and in 6.2% after 6 months. The latter rate is certainly too low, however, as 26 of 63 patients were lost to follow-up. A national fistula task force has been set up in Malawi. PMID- 17869257 TI - Prevention and treatment of obstetric fistula: Identifying research needs and public health priorities. PMID- 17869258 TI - Primed polymorphonuclear leukocytes constitute a possible link between inflammation and oxidative stress in hyperlipidemic patients. AB - BACKGROUND: Oxidative stress (OS) and chronic inflammation are involved and contribute to the development of atherosclerosis. Primed polymorphonuclear leukocytes (PMNLs) are a possible source for superoxide radicals and inflammatory mediators, hence can promote OS and inflammation. The involvement of primed PMNLs in clinical states associated with high risk for developing cardiovascular disease and atherosclerosis, such as hypertension, renal failure and diabetes has been described, however, little is known about PMNLs characteristics in hyperlipidemic patients. METHODS: Hyperlipidemic patients and healthy control (HC) subjects were enrolled in this cross-sectional study. PMNL priming was estimated by measuring the rate of superoxide release and by levels of membrane CD11b. PMNL priming and myeloperoxidase (MPO) levels served as OS indices. Inflammation was linked to peripheral white blood cells and PMNL counts and to apoptosis. Systemic inflammation was estimated by blood levels of fibrinogen, C reactive protein (CRP), transferrin and albumin. PMNL priming and inflammation parameters were related to the severity of hyperlipidemia. RESULTS: PMNLs from hyperlipidemic patients are primed compared to HC. A decrease in PMNL-MPO levels with increased levels of serum MPO were found in hyperlipidemic patients. Leukocyte counts tended to be higher in hyperlipidemic patients with increased PMNL apoptosis. PMNL priming and fibrinogen levels correlated positively with the severity of hyperlipidemia (r=0.32, P=0.02 for CD11b vs. cholesterol and r=0.38, P=0.009 for CD11b vs. LDL-c; r=0.35, P=0.01 for fibrinogen vs. cholesterol and r=0.3, P=0.03 for superoxide release vs. LDL-c). CONCLUSION: PMNLs are primed in hyperlipidemic patients contributing to OS and inflammation in these patients. This study highlights primed PMNLs as an additional risk factor for promoting atherosclerosis in hyperlipidemic patients. PMID- 17869259 TI - Histological topographical comparisons of atherosclerosis progression in juveniles and young adults. AB - BACKGROUND: The histologically topographic comparisons on atherosclerosis progression among three anatomical sites, mid-thoracic and lower abdominal aorta and left anterior descending coronary artery (LAD) were performed using a young population (age 15-34 years) from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. METHODS AND RESULTS: The histological classification based on the American Heart Association grading scheme showed that in the thoracic aorta type 2 lesions (numerous macrophage foam cells with fine particles but no pools of extracellular lipid) appeared in the first 10-year age group, with no significant change in prevalence in the next 10 years. Lesions greater than type 2 were rarely seen in the thoracic aorta. Although type 2 lesions appeared later in the LAD than in the aorta, the lesions within the LAD progressed rapidly to more advanced lesions (types 4 and 5) or atheroma. Lesion development in the abdominal aorta was intermediate to lesion development in the thoracic aorta and the LAD. CONCLUSIONS: The most striking topographic difference on lesion progression among the three anatomical sites was the vulnerability of type 2 lesions to progress into advanced lesions. The histology study, including immunohistochemistry limited to the type 2 lesions suggested that lesion progression was related to the intimal thickness and the amount of collagen but not to the number of macrophage foam cells. PMID- 17869260 TI - 6-oxy-(acetyl piperazine) fluorescein as a new fluorescent labeling reagent for free fatty acids in serum using high-performance liquid chromatography. AB - A new fluorescein-based fluorescent derivatizating reagent, 6-oxy-(acetyl piperazine) fluorescein (APF), has been designed, synthesized and developed for carboxylic acid labeling. It was used as a pre-column derivatizing reagent for the determination of seven free fatty acids (lauric acid, myristic acid, arachidonic acid, linoleic acid, palmitic acid, oleic acid, and stearic acid) with high-performance liquid chromatography (HPLC). The derivatization reaction of APF with seven fatty acids was completed at 60 degrees C for 1 h using 1-ethyl 3-(3-dimethylaminopropyl)carbodiimide (EDC) as the condensing reagent. On a C18 column, the derivatives of APF with seven free fatty acids could be separated completely in 22 min using a mobile phase of methanol-water (88:12, v/v) containing 7 mmol L(-1) pH 6.5 Na2HPO4-H3Cit3 buffer with fluorescence detection at lambdaex/lambdaem=467/512 nm. The detection limits could reach 0.1-6.4 nmol L( 1) (signal-to-noise=3). This reagent was applied to the determination of the free fatty acids in human serum samples with satisfying recovery efficiencies varying from 93 to 105%. PMID- 17869261 TI - Quality by design--thermodynamic modelling of chromatographic separation of proteins. AB - A desired goal of the PAT framework is to design and develop well-understood processes that will consistently ensure a predefined quality at the end of the manufacturing process. Such procedures would be consistent with the basic tenet of quality by design and could reduce risks to quality and regulatory concerns while improving efficiency. To support a more in-depth understanding of the design and development of a chromatographic purification process the paper discusses the general thermodynamic principles of ligand-binding and models of multi-component adsorption in ion-exchange and hydrophobic chromatography. The parameters in the models are easy to determine and have a well-defined physical significance. Examples demonstrate how the model parameters can be determined from experimental data and in order to validate the model, simulated chromatograms are compared to the corresponding experimental chromatograms. Finally it is demonstrated how a simulation can be used to explain an aberration. PMID- 17869262 TI - Counterion volume effects in mixed electrical double layers. AB - When a monolayer of negatively charged surfactant molecules is brought in contact with an aqueous solution containing mixtures of counterions of different size and valency, very large deviations from Poisson-Boltzmann theory (PBT) develop at a high surface charge, with the smaller counterion outcompeting the larger one (even if divalent) near the interface, leading to counterion segregation [V.L. Shapovalov, G. Brezesinski, J. Phys. Chem. B 110 (2006) 10032]. We use a modified PBT that empirically includes an extended Carnahan-Starling equation-of-state to describe hard-sphere interactions in electrical double layers containing ions of different size and charge. Model calculations are made for ion concentration profiles, free energies, surface pressures, and differential capacities. At high surface charge, volume interactions become important, leading to significant deviations from PBT. In contrast to PBT, at high surface charge, contributions to energy and pressure are no longer mainly entropic, but instead volume and electrostatic field effects now dominate. When the hydrated size of the divalent ion is used as an adjustable parameter, the theory is in good agreement with the experimental data. PMID- 17869263 TI - Study of the growth process of in situ polyaniline deposited films. AB - Polyaniline (PAni) thin films were deposited onto BK7 glass substrates using the in situ deposition technique. The control of the time and the aniline concentration in the PAni polymerization reaction on the film deposition allowed us to prepare films with different thickness, down to approximately 25 nm. The film growth process was monitored by measuring the UV-vis spectra and the AFM height profiles of the film surface. The curves of adsorption kinetics were analyzed with the Avrami's model, yielding an exponent n=3, thus indicating nucleation of spheroids at the initial stages of polymerization that grow through a diffusion process. AFM images of the surface height profiles corroborate this hypothesis, with spheroids growing with no preferred orientation during the in situ deposition. PMID- 17869264 TI - Identification, characterization, and developmental regulation of two storage proteins in the bamboo borer Omphisa fuscidentalis. AB - Two insect storage proteins, OfSP1 (75 kDa) and OfSP2 (72 kDa), were purified using three different chromatographies from the hemolymph of Omphisa fuscidentalis larvae during diapause, and their genes were cloned. OfSP1 and OfSP2 concentrations in the hemolymph were high during diapause. During pupation, OfSP1 levels decreased in the male hemolymph and disappeared from the female hemolymph. OfSP1 and OfSP2 mRNA levels in the fat bodies were low during the third instar, but increased greatly during the fourth and fifth larval instars. During diapause, mRNA expression continued at a lower level than during the feeding period. The injection of 20-hydroxyecdysone (20E) into diapausing larvae caused an increase in OfSP1 and OfSP2 mRNA levels 2-3 days post-injection, followed by a decrease in expression until pupation, which occurred 2-4 days thereafter. When larvae were treated with juvenile-hormone analog (JHA), OfSP1 and OfSP2 mRNA levels gradually decreased until the onset of pupation. In Omphisa, OfSP1 and OfSP2 proteins are produced and released by the larval fat bodies in the fourth and fifth-instar larvae, and the proteins accumulate in the hemolymph until the insects enter diapause. OfSP1 may be reabsorbed by the fat bodies at the end of diapause for subsequent re-use during pupation. PMID- 17869265 TI - Selection of Beauveria bassiana isolates to control Alphitobius diaperinus. AB - This paper presents results on isolates of the entomopathogenic fungus Beauveria bassiana for Alphitobius diaperinus (Coleoptera: Tenebrionidae) control. Of the 30 isolates tested, four (CG 71, CG 152, UNIOESTE 4, and UNIOESTE 40) resulted in mortality rates >or= 40% within 10 days. These mortality rates could be considered high because of the resistance of these species to B. bassiana. Tests were conducted using these isolates to estimate LC(50), mortality rate over time, vegetative growth, and conidial production on artificial medium and on insects. Isolates CG 71, CG 152, and UNIOESTE 4 showed the best performance and great potential to be used in an integrated management program in poultry farms to control A. diaperinus. Also, the molecular profiles of 12 isolates were analyzed using the RAPD technique. The high-virulence isolates presented a more homogeneous RAPD pattern than the others. Genetic sequencing of the ITS region was performed for one of the virulent isolates (UNIOESTE 4) and compared with sequences deposited at the NCBI database, confirming its taxonomical position as belonging to B. bassiana Clade A. PMID- 17869266 TI - EMMPRIN mediates beta-adrenergic receptor-stimulated matrix metalloproteinase activity in cardiac myocytes. AB - Extracellular matrix metalloproteinase inducer (EMMPRIN) expression is increased in myocardium from patients with dilated cardiomyopathy and animal models of heart failure. However, little is known about the regulated expression or functional role of EMMPRIN in the myocardium. In rat cardiac cells, EMMPRIN is expressed on myocytes but not endothelial cells or fibroblasts. Therefore, we tested the hypothesis that EMMPRIN expression regulates matrix metalloproteinase (MMP) activity in rat ventricular myocytes in vitro. In adult rat ventricular myocytes (ARVM), beta-adrenergic receptor (betaAR) stimulation and H(2)O(2) (24 h) each increased EMMPRIN expression as assessed by immunoblotting. Pretreatment with a catalase/superoxide dismutase mimetic or adenoviral-mediated expression of catalase or a dominant-negative c-jun N-terminal kinase-1 (JNK) mutant inhibited the betaAR- and H(2)O(2)-stimulated increases in EMMPRIN expression suggesting that EMMPRIN expression is regulated via a reactive oxygen species-dependent JNK pathway. To determine whether EMMPRIN expression regulates matrix metalloproteinase (MMP) activity, EMMPRIN activity was inhibited by adenoviral expression of an inhibitory mutant of EMMPRIN. Expression of mutant EMMPRIN inhibited the betaAR-stimulated increases in MMP2 expression and zymographic MMP activity. Thus, in cardiac myocytes betaAR stimulation induces the expression of EMMPRIN via the ROS-dependent activation of JNK. The resulting increase in EMMPRIN activity stimulates MMP expression and activity. These findings suggest that in the myocardium the regulated expression of EMMPRIN is a determinant of MMP activity and may thus play a role in myocardial remodeling. PMID- 17869267 TI - Characterization of a double dockerin from the cellulosome of the anaerobic fungus Piromyces equi. AB - The assembly into supramolecular complexes of proteins having complementary activities is central to cellular function. One such complex of considerable biological and industrial significance is the plant cell wall-degrading apparatus of anaerobic microorganisms, termed the cellulosome. A central feature of bacterial cellulosomes is a large non-catalytic protein, the scaffoldin, which contains multiple cohesin domains. An array of digestive enzymes is incorporated into the cellulosome through the interaction of the dockerin domains, present in the catalytic subunits, with the cohesin domains that are present in the scaffoldin. By contrast, in anaerobic fungi, such as Piromyces equi, the dockerins of cellulosomal enzymes are often present in tandem copies; however, the identity of the cognate cohesin domains in these organisms is unclear, hindering further biotechnological development of the fungal cellulosome. Here, we characterise the solution structure and function of a double-dockerin construct from the P. equi endoglucanase Cel45A. We show that the two domains are connected by a flexible linker that is short enough to keep the binding sites of the two domains on adjacent surfaces, and allows the double-dockerin construct to bind more tightly to cellulosomes than a single domain and with greater coverage. The double dockerin binds to the GH3 beta-glucosidase component of the fungal cellulosome, which is thereby identified as a potential scaffoldin. PMID- 17869268 TI - Structural elements underlying the high binding affinity of human cytomegalovirus UL18 to leukocyte immunoglobulin-like receptor-1. AB - Human cytomegalovirus (HCMV) encodes UL18, a major histocompatibility complex (MHC) class I homologue that binds to the leukocyte immunoglobulin-like receptor (LIR)-1 (also called ILT2/CD85j/LILRB1), an inhibitory receptor expressed on myeloid and lymphoid immune cells. The molecular basis underlying the high affinity binding of UL18 to LIR-1, compared to MHC class I molecules (MHC-I), is unclear. Based on a comparative structural analysis of a molecular model of UL18 with the crystal structure of the HLA-A2/LIR-1 complex, we identified three regions in UL18 influencing interaction with LIR-1. Comparison of the relative binding affinities of mutated UL18 proteins to LIR-1 demonstrated the importance of specific residues in each region. Substitution of residues K42/A43 and Q202, localized in the alpha1 and alpha3 domains, respectively, reduced binding affinity to LIR-1 nearly by half. The model also suggested the formation of an additional disulfide bridge in the alpha3 domain of UL18 between residues C240 and C255, not present in MHC-I. Substitution of either cysteine residue prevented association of UL18 to beta2m, abolishing binding to LIR-1. All observed differences in binding affinities translated directly into functional consequences in terms of inhibition of IFN-gamma production by T cells, mediated through the UL18-LIR-1 interaction. The larger amount of interacting regions, combined with an increased stability of the alpha3 and beta2m domains allow a higher recognition affinity of UL18 by LIR-1. PMID- 17869269 TI - X-ray structure of a NF-kappaB p50/RelB/DNA complex reveals assembly of multiple dimers on tandem kappaB sites. AB - We describe here the X-ray crystal structure of NF-kappaB p50/RelB heterodimer bound to a kappaB DNA. Although the global modes of subunit association and kappaB DNA recognition are similar to other NF-kappaB/DNA complexes, this complex reveals distinctive features not observed for non-RelB complexes. For example, Lys274 of RelB is removed from the protein-DNA interface whereas the corresponding residues in all other subunits make base-specific contacts. This mode of binding suggests that RelB may allow the recognition of more diverse kappaB sequences. Complementary surfaces on RelB and p50, as revealed by the crystal contacts, are highly suggestive of assembly of multiple p50/RelB heterodimers on tandem kappaB sites in solution. Consistent with this model our in vitro binding experiments reveal optimal assembly of two wild-type p50/RelB heterodimers on tandem HIV kappaB DNA with 2 bp spacing but not by a mutant heterodimer where one of the RelB packing surface is altered. We suggest that multiple NF-kappaB dimers assemble at diverse kappaB promoters through direct interactions utilizing unique protein-protein interaction surfaces. PMID- 17869271 TI - Characterization of a novel Cullin5 binding domain in HIV-1 Vif. AB - Human immunodeficiency virus tyoe 1 (HIV-1) Vif counteracts host restriction cytidine deaminase (APOBEC3G) A3G by co-opting the cellular ubiquitin-proteasome machinery. Vif utilizes a viral-specific BC-box to recruit ElonginB-ElonginC and a novel zinc-binding HCCH motif to recruit Cullin5 (Cul5) to form an E3 ubiquitin ligase targeting A3G for polyubiquitination and subsequently proteasomal degradation. To determine the structural requirements in HIV-1 Vif HCCH motif for Cul5 binding and Vif function, we investigated the arrangement of the His and Cys residues, the role of the spacing between them, and the requirement for the conserved residues. Our data demonstrate that exchanging Cys for His and vice versa in the highly conserved Zn-coordinating HCCH motif disrupted Vif function and interaction with Cul5. Moreover, the maintenance of both conserved residues and spacing within the HCCH motif is critical for Vif function. We have identified a "viral Cul5 box" with consensus Hx2YFxCFx4Phix2APhix7-8Cx5H that is required for Cul5 selection and subsequent A3G degradation. This novel motif may represent a potential new target for anti-viral drug development. PMID- 17869270 TI - Insights from atomic-resolution X-ray structures of chemically synthesized HIV-1 protease in complex with inhibitors. AB - The human immunodeficiency virus 1 (HIV-1) protease (PR) is an aspartyl protease essential for HIV-1 viral infectivity. HIV-1 PR has one catalytic site formed by the homodimeric enzyme. We chemically synthesized fully active HIV-1 PR using modern ligation methods. When complexed with the classic substrate-derived inhibitors JG-365 and MVT-101, the synthetic HIV-1 PR formed crystals that diffracted to 1.04- and 1.2-A resolution, respectively. These atomic-resolution structures revealed additional structural details of the HIV-1 PR's interactions with its active site ligands. Heptapeptide inhibitor JG-365, which has a hydroxyethylamine moiety in place of the scissile bond, binds in two equivalent antiparallel orientations within the catalytic groove, whereas the reduced isostere hexapeptide MVT-101 binds in a single orientation. When JG-365 was converted into the natural peptide substrate for molecular dynamic simulations, we found putative catalytically competent reactant states for both lytic water and direct nucleophilic attack mechanisms. Moreover, free energy perturbation calculations indicated that the insertion of catalytic water into the catalytic site is an energetically favorable process. PMID- 17869272 TI - Serum heart-fatty acid binding protein levels in patients with Lewy body disease. AB - OBJECTIVE: In order to examine a possible role of serum heart-fatty acid binding protein (H-FABP) in patients with Lewy body disease, we measured serum levels of H-FABP in patients with dementia with Lewy bodies (DLB), Parkinson's disease (PD), and Alzheimer's disease (AD). METHODS: Serum levels of H-FABP were measured using a solid-phase enzyme-linked immunoassay. Iodine-123 metaiodobenzylguanidine ((123)I-MIBG) cardiac scintigraphy was performed on each patient and the heart to mediastinum (H/M) ratio was calculated. Receiver operating characteristic (ROC) analysis was used to calculate the optimal cutoff values of the H-FABP between DLB and AD patients. Independent predictive variables for serum H-FABP levels were analyzed using multivariate regression analysis. RESULTS: Serum levels of H FABP were significantly higher in DLB patients and PD patients than in AD patients. H/M ratios of the DLB and PD patients were significantly lower than those of AD patients. The diagnostic value of the serum H-FABP levels between AD and DLB patients was inferior to that of the delayed H/M ratio of (123)I-MIBG cardiac scintigraphy. Multivariate regression analysis revealed that the delayed H/M ratio predicted serum H-FABP levels in the PD patients. CONCLUSIONS: Examination of serum H-FABP levels did not allow discrimination between DLB and AD patients. Cardiac sympathetic nerve dysfunction may be associated with elevation of serum H-FABP in Lewy body disease patients. PMID- 17869273 TI - A mathematical model for human nucleotide excision repair: damage recognition by random order assembly and kinetic proofreading. AB - A mathematical model of human nucleotide excision repair was constructed and validated. The model incorporates cooperative damage recognition by RPA, XPA, and XPC followed by three kinetic proofreading steps by the TFIIH transcription/repair factor. The model yields results consistent with experimental data regarding excision rates of UV photoproducts by the reconstituted human excision nuclease system as well as the excision of oligonucleotides from undamaged DNA. The model predicts the effect that changes in the initial concentrations of repair factors have on the excision rate of damaged DNA and provides a testable hypothesis on the biochemical mechanism of cooperativity in protein assembly, suggesting experiments to determine if cooperativity in protein assembly results from an increased association rate or a decreased dissociation rate. Finally, a comparison between the random order assembly with kinetic proofreading model and a sequential assembly model is made. This investigation reveals the advantages of the random order assembly/kinetic proofreading model. PMID- 17869274 TI - Coreceptor CD8-driven modulation of T cell antigen receptor specificity. AB - The CD8 coreceptor modulates the interaction between the T cell antigen receptor (TCR) and peptide-major histocompatibility class I (pMHCI). We present evidence that CD8 not only modifies the affinity of cognate TCR/pMHCI binding by altering both the association rate and the dissociation rate of the TCR/pMHCI interaction, but modulates the sensitivity (triggering threshold) of the TCR as well, by recruiting TCR/pMHCI complexes to membrane microdomains at a rate which depends on the affinity of MHCI/CD8 binding. Mathematical analysis of these modulatory effects indicates that a T cell can alter its functional avidity for its agonists by regulating CD8 expression, and can rearrange the relative potencies of each of its potential agonists. Thus we propose that a T cell can specifically increase its functional avidity for one agonist, while decreasing its functional avidity for other potential ligands. This focussing mechanism means that TCR degeneracy is inherently dynamic, allowing each TCR clonotype to have a wide range of agonists while avoiding autorecognition. The functional diversity of the TCR repertoire would therefore be greatly augmented by coreceptor-mediated ligand focussing. PMID- 17869275 TI - Prediction of group patterns in social mammals based on a coalescent model. AB - This study describes a statistical model which assumes that mammal group patterns match with groups of genetic relatives. Given a fixed sample size, recursive algorithms for the exact computation of the probability distribution of the number of groups are provided. The recursive algorithms are then incorporated into a statistical likelihood framework which can be used to detect and quantify departure from the null-model by estimating a clustering parameter. The test is then applied to ecological data from social herbivores and carnivores. Our findings support the hypothesis that genetic relatedness is likely to predict group patterns when large mammals have few or no predators. PMID- 17869276 TI - T cell development in the thymus: from periodic seeding to constant output. AB - T cell development occurs in the thymus throughout life. Recent experimental findings show that the seeding of the thymus by multi-potent stem cells from the bone marrow is periodic rather than continuous, as previously assumed. However it is well known that the output rate of cells from the thymus is relatively constant. A quantitative model is used to verify the current hypotheses regarding T cell development in the steady state mouse thymus. The results show that the thymus could be at a periodic steady state with out-of-phase thymocyte populations. Experiments to examine possible periodic fluctuations in the thymus are proposed and methods for further analysis are outlined. PMID- 17869288 TI - An independent analysis of flexible cystoscope repairs and cost. AB - PURPOSE: To establish the repair patterns of flexible cystoscopes we performed a systematic review of repairs performed at an independent endoscope repair company. MATERIALS AND METHODS: Repair and cost data for 2000 to 2004 were obtained from an independent endoscope repair company. All cystoscopes underwent a detailed inspection using a preset protocol and the frequency of individual repair descriptions was extracted from a computer database. RESULTS: A total of 1,150 repairs were performed on the Olympus CYF (3%), CYF-2 (21%), CYF-3 (56%) and CYF-4 (20%) flexible cystoscopes. Repairs to the distal tip (28% of all repairs) most commonly involved the bending rubber or outer polymer sheath. Repairs to the hand control segment (14% of all repairs) most commonly involved the ocular. Repairs for image (14% of all repairs) and deflection (9%) were most commonly performed on the fiberoptic bundle and wires, respectively. Repairs to the deflection apparatus comprised a significantly greater proportion of total repairs in the early CYF models than in the CYF-4 model (10% to 12% vs 3%, p <0.01, chi-square 10.73). Less than 1% of all cystoscopes needed more than 2 repairs. CONCLUSIONS: Olympus cystoscopes require repair every 2 to 3 years and they appear to be durable. The distal deflection tip, specifically the outer bending rubber, is the most common site of flexible cystoscope damage. Although it appears that significant improvements have been made to the deflection apparatus, the number of repairs to other areas has not changed significantly with time. Improvements in form and function of the distal tip, the hand control segment and the fiberoptic bundles may enhance the durability of flexible cystoscopes. PMID- 17869289 TI - Ideal culture time for improvement in sperm motility from testicular sperm aspirates of men with azoospermia. AB - PURPOSE: The motility of testicular derived spermatozoa reflects viability and predicts success during intracytoplasmic sperm injection. Although improvements in sperm motility are seen after incubation for extended periods, no guidelines suggest duration or media use for optimal improvement in motility. MATERIALS AND METHODS: Between July 1999 and February 2005 testicular aspirations were performed on 95 men with azoospermia, including 51 with obstructive azoospermia and 44 with nonobstructive azoospermia. Sperm motility was determined at initial collection and following incubation for 24 or 48 hours in processing media or Ham's F10 + protein. A mixed regression model controlling for testis side, media and baseline motility was created to analyze the change in motility between 24 and 48 hours. RESULTS: Mean motility improved from 3% to 20% at 24 hours and 25% at 48 hours for OA cases and from 0% to 5% at 24 hours and 11% at 48 hours for nonobstructive azoospermia cases. The improvement in motility from 24 to 48 hours was significant for obstructive azoospermia cases (p = 0.001). While media was a nonsignificant factor in regression models, when patients were grouped into categories of motility change there was a significantly better response to F10 compared to processing media (p = 0.03). CONCLUSIONS: Incubation in processing media or Ham's F10 + albumin media improves sperm motility with significant improvement noted between 24 and 48 hours for obstructive azoospermia cases. Ham's F10 + albumin media may provide extra benefit for cases of nonobstructive azoospermia or nerve injury. These results suggest the ideal timing of oocyte retrieval for intracytoplasmic sperm injection correlates with 48-hour sperm incubation for obstructive azoospermia cases, and 24 hours for nonobstructive azoospermia and nerve injury cases. PMID- 17869290 TI - Midodrine improves ejaculation in spinal cord injured men. AB - PURPOSE: We evaluated the effect of the alpha1-adrenergic agonist midodrine given orally for anejaculation in spinal cord injured men. MATERIALS AND METHODS: A total of 185 spinal cord injured patients who reported absent ejaculation during sexual intercourse and who failed to respond to penile vibratory stimulation were treated with midodrine 30 to 120 minutes before a new stimulation. The procedure was repeated weekly, increasing doses by 7.5 mg to a maximum of 30 mg. Cardiovascular effects were monitored throughout the procedure. RESULTS: Antegrade or retrograde ejaculation was achieved in 102 spinal cord injured men (64.6%). A positive response was more frequent in patients with complete lesions (American Spinal Injury Association A) and upper motor neuron lesions above T10. Midodrine induced a significant but moderate increase (maximum 10 mm Hg) in mean arterial pressure in all patients. The highest systolic blood pressure (more than 200 mm Hg) was seen in patients with quadriplegia. No other significant side effect was recorded. The average dose of midodrine required for ejaculation was 18.7 mg. CONCLUSIONS: Midodrine is a safe and efficient adjunct to penile vibratory stimulation for anejaculation in spinal cord injured patients. PMID- 17869291 TI - Responsiveness and minimum important differences for the erection quality scale. AB - PURPOSE: We evaluated the responsiveness and treatment sensitivity of the Erection Quality Scale, and provided further psychometric validation of this scale. MATERIALS AND METHODS: An 8-week, placebo controlled, randomized clinical trial investigating the efficacy and safety of vardenafil in patients with erectile dysfunction was performed. The Erection Quality Scale, together with a number of other patient and partner questionnaires, was administered at a screening visit, at baseline, and weeks 4 and 8 of treatment. Erection Quality Scale responsiveness was investigated by evaluating treatment induced changes and modeling using ANCOVA. Internal consistency, convergent and discriminant validity, and minimum important difference of the Erection Quality Scale were also assessed. RESULTS: Efficacy evaluations demonstrated that the Erection Quality Scale was sufficiently responsive to differentiate the treatment benefits of vardenafil compared with placebo. Internal consistency for the Erection Quality Scale total score was similar across visits, with values high enough to suggest reliability of items included in the scale. Discriminant validity of the Erection Quality Scale total score was demonstrated, with a high correlation with the erectile function domain of the International Index of Erectile Function (0.88, p <0.0001) and negligible correlations with clinical measures assumed to be unrelated to erection quality. All Erection Quality Scale total score comparisons substantially exceeded the 5-point minimum important difference estimate. CONCLUSIONS: The Erection Quality Scale was responsive and internally consistent, and demonstrated convergent and discriminant validity. Furthermore, this instrument provided a unique contribution to the measurement of erection quality compared to the International Index of Erectile Function. This study provides strong evidence supporting the use of the Erection Quality Scale in clinical trials. PMID- 17869292 TI - Urogenital disorders associated with gut failure and intestinal transplantation. AB - PURPOSE: Intestinal transplantation has been increasingly performed in patients with short bowel syndrome and irreversible gut failure with successful outcomes. In parallel a common association was observed between gut failure and different urological disorders. To our knowledge this study is the first to address such an important clinical observation with special reference to the underlying disease. MATERIALS AND METHODS: The medical records of 175 consecutive adult intestinal recipients were reviewed. Data were compiled and described according to the documented urogenital disorder, cause of intestinal failure and treatment modality, including transplantation. RESULTS: Of the patients 43 experienced a total of 53 urogenital disorders for an overall incidence of 25%, including 24 (56%) who had the disorder before referral and 19 (44%) in whom the morbidity developed as a result of transplantation. Interestingly hypercoagulability, pseudo-obstruction, Crohn's disease and Gardner's syndrome were the underlying urogenital and intestinal disorder pathologies in 6.3% of the study patients. Treatment for prior urogenital disorders, including malignancy, precipitated intestinal failure in 3.4% of the referred patients. Reciprocally surgical treatment for the primary intestinal disease and management of gut failure by total parenteral nutrition, followed by transplantation, resulted in different urogenital complications in 17.7% of the total population with an 8.6% incidence of chronic renal failure. CONCLUSIONS: Gut failure and intestinal transplantation are commonly associated with different urogenital disorders. Accordingly a designated urological service should be considered part of the multidisciplinary team required for treating this unique population. PMID- 17869293 TI - Novel technique for hand assisted laparoscopic right donor nephrectomy. AB - PURPOSE: Most surgeons divide the renal vein with a laparoscopic stapler during laparoscopic donor nephrectomy. The right renal vein is usually shorter than the left one and using the stapler on the right side can result in a higher incidence of vascular complications for right kidney recipients. We present our experience with a new technique for hand assisted laparoscopic right donor nephrectomy. MATERIALS AND METHODS: We designed a new vascular clamp to be completely inserted into the peritoneal cavity through the hand port incision in hand assisted laparoscopy. The renal vein with a cuff of the inferior vena cava was then excised. The defect in the inferior vena cava was sutured intracorporeally. RESULTS: A total of 80 kidney donors underwent hand assisted laparoscopic right donor nephrectomy using the new technique. Mean +/- SD operative time was 184 +/- 36 minutes. Operative time was decreased in the last 30 patients to 152 +/- 22 minutes. Intracorporeal suture time on the inferior vena cava was 16 +/- 3 minutes. No intraoperative complications were noted and there was no partial or total graft loss. Mean blood loss was 50 +/- 35 cc. Mean warm ischemia time was 4 +/- 2 minutes. Hospital discharge was on postoperative day 1 or 2 in 81% of patients. Graft function was normal in 78 recipients with a day 5 postoperative serum creatinine of 1.6 +/- 0.9 mg/dl. Two recipients showed delayed graft function and were treated medically. CONCLUSIONS: This technique for hand assisted laparoscopic right donor nephrectomy has proved to be safe and reproducible. We recommend practicing laparoscopic inferior vena cava suturing in the animal laboratory before performing it in humans. PMID- 17869294 TI - Office based transurethral needle ablation of the prostate with analgesia and local anesthesia. AB - PURPOSE: We evaluated the efficacy and feasibility of performing office based transurethral needle ablation of the prostate with analgesia and local anesthesia. MATERIALS AND METHODS: A total of 56 consecutive patients underwent transurethral needle ablation of the prostate for symptomatic benign prostatic hyperplasia. Oral rofecoxib (50 mg) and ciprofloxacin (250 mg) were administered before the procedure with 25 mg hydroxyzine and 50 to 100 mg meperidine intramuscularly. A combination of 2% lidocaine solution and jelly was used for anesthesia. Patients rated discomfort during anesthesia administration and the procedure using a 10-point scale of 0--no discomfort to 10--the worst pain/discomfort ever experienced in the patient life. Overall satisfaction with the procedure was assessed with a 4-point scale of 1--very satisfactory to 4- very unsatisfactory. Followup was 12 months for uroflow and 36 months for International Prostate Symptom Score. RESULTS: The mean age of 47 patients was 65.4 years. Mean discomfort ratings were 3.6 and 4.9 for anesthesia administration and the procedure, respectively. Average operative time was 34.4 minutes, excluding anesthesia administration. The mean overall satisfaction score was 1.5. The mean preoperative International Prostate Symptom Score was 23.1, which improved to 10.9, 11.2, 12.3, 13.8 and 11.3 at 3, 6, 12, 24 and 36 months, respectively. Mean maximum uroflow improved from 8.2 ml/sec at baseline to 12.8, 13.9 and 13.3 ml/sec at 3, 6 and 12 months, respectively. CONCLUSIONS: Administration of an intramuscular narcotic combined with oral analgesic and topical lidocaine provided adequate pain control for transurethral needle ablation of the prostate, making it a feasible office procedure. PMID- 17869295 TI - The effect of doxazosin, finasteride and combination therapy on nocturia in men with benign prostatic hyperplasia. AB - PURPOSE: We evaluated the effectiveness of single or combination drug therapy on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 3,047 men with lower urinary tract symptoms/benign prostatic hyperplasia enrolled in the Medical Therapy of Prostatic Symptoms trial were randomly assigned to receive doxazosin alone, finasteride alone, combination therapy or placebo. Treatment effectiveness was assessed according to intent to treat by mean reduction in self-reported nightly nocturia at 1 and 4 years. A subgroup analysis by age (younger than 70 vs 70 years old or older) was also performed. RESULTS: Of the men 2,583 reported 1 or more episodes of nocturia and finished 12 or more months of the trial. Mean nocturia was similar in all groups at baseline. Mean nocturia was reduced at 1 year by 0.35, 0.40, 0.54 and 0.58 in the placebo, finasteride, doxazosin and combination groups, respectively. Reductions with doxazosin and combination therapy were statistically greater than with placebo (p <0.05). At 4 years nocturia was also significantly reduced in patients treated with doxazosin and combination therapy (p <0.05 vs placebo). In men older than 70 years (495) all drugs significantly reduced nocturia at 1 year (finasteride 0.29, doxazosin 0.46 and combination 0.42) compared to placebo (0.11, p <0.05). CONCLUSIONS: Doxazosin and combination therapy reduced nocturia more than placebo, but the net benefit of active drug compared to placebo was often modest with a net difference of less than 0.20 fewer nightly nocturia episodes at 1 and 4 years. Findings in men 70 years old or older were similar, with an even smaller effect observed for finasteride. PMID- 17869296 TI - Vardenafil improves urodynamic parameters in men with spinal cord injury: results from a single dose, pilot study. AB - PURPOSE: We assessed urodynamic changes after vardenafil administration in spinal cord injured male patients on oxybutynin treatment. MATERIALS AND METHODS: We performed a single center, randomized, double-blind, placebo controlled trial in 25 patients with spinal cord injury who had erectile dysfunction and micturition disorders. A baseline urodynamic test was performed as well as a second urodynamic test 1 to 3 hours after the administration of 20 mg vardenafil and placebo in 15 and 10 cases, respectively. In all patients standard oral oxybutynin administration was not discontinued. Statistical assessment included the 3 urodynamic parameters maximum detrusor pressure during voiding, maximum cystometric capacity and detrusor overactivity volume. RESULTS: Placebo administration did not affect urodynamic parameters. After vardenafil administration maximum detrusor pressure was significantly decreased (59.3 vs 52.1 cm H(2)O, p <0.001) and maximum cystometric capacity considerably improved (233.5 vs 272 ml, p <0.001). The most dramatic variations were observed for detrusor overactivity volume (174 vs 218 ml, p <0.0001). In 7 patients with American Spinal Injury Association classification A and spinal cord injury above T6 we observed the most significant improvement in the evaluated urodynamic items, including maximum detrusor pressure 57 vs 52 cm H(2)O (p = 0.039), maximum cystometric capacity 253 vs 296 ml (p = 0.004) and detrusor overactivity volume 177 vs 229 ml (p = 0.003). CONCLUSIONS: This trial demonstrates that in spinal cord injured patients a single 20 mg vardenafil administration achieved a significant decrease in maximum detrusor pressure, an improvement in maximum cystometric capacity and a remarkable increase in detrusor overactivity volume value. PMID- 17869297 TI - Bipolar transurethral resection in saline--an alternative surgical treatment for bladder outlet obstruction? AB - PURPOSE: The transurethral resection in saline system uses bipolar energy for transurethral prostate resection, thus, avoiding the need for glycine irrigation and its associated complications. We compared the clinical efficacy and safety of bipolar transurethral resection in saline and of monopolar transurethral prostate resection for symptomatic benign prostate hyperplasia. MATERIALS AND METHODS: From January 2005 to June 2006, 238 consecutive patients with symptomatic benign prostate hyperplasia were randomized into a prospective, controlled trial comparing the 2 treatment modalities. Patient demographics, operative time, hospital stay and complications were noted. Serum hemoglobin and electrolytes were determined in all patients immediately before and after the endoscopic procedure. RESULTS: During 18 months 120 patients were randomized to the conventional transurethral prostate resection group and 118 were randomized to the transurethral resection in saline group. Patient profiles, weight of resected prostatic tissue and duration of hospitalization were similar in the 2 groups. The decrease in serum sodium and serum chloride was statistically significantly greater in the transurethral prostate resection group than in the transurethral resection in saline group (each p = 0.05). The transurethral resection in saline procedure required significantly more time (mean 56 vs 44 minutes, p <0.01). There was 1 case (0.8%) of transurethral resection syndrome in the transurethral prostate resection group but none in the transurethral resection in saline group. Postoperative bleeding did not significantly differ between the 2 groups. Clot retention was observed in 6 (5%) and 4 patients (3%) in the transurethral prostate resection and transurethral resection in saline group, respectively. Two repeat interventions were required in the transurethral prostate resection group. CONCLUSIONS: The bipolar transurethral resection in saline system is as efficacious as monopolar transurethral prostate resection but it is safer than the latter because of the lesser decrease in postoperative hypernatremia and the smaller risk of transurethral resection syndrome. However, probably due to technical reasons, transurethral resection in saline operative time is significantly longer. PMID- 17869298 TI - Results of sacral neuromodulation therapy for urinary voiding dysfunction: outcomes of a prospective, worldwide clinical study. AB - PURPOSE: This 5-year, prospective, multicenter trial evaluated the long-term safety and efficacy of sacral neuromodulation in patients with refractory urge incontinence, urgency frequency and retention. MATERIALS AND METHODS: A total of 17 centers worldwide enrolled 163 patients (87% female). Following test stimulation 11 patients declined implantation and 152 underwent implantation using InterStim. Of those treated with implantation 96 (63.2%) had urge incontinence, 25 (16.4%) had urgency frequency and 31 (20.4%) had retention. Voiding diaries were collected annually for 5 years. Clinical success was defined as 50% or greater improvement from baseline in primary voiding diary variable(s). RESULTS: Data for all implanted cases were reported. For patients with urge incontinence mean leaking episodes per day decreased from 9.6 +/- 6.0 to 3.9 +/- 4.0 at 5 years. For patients with urgency frequency mean voids per day decreased from 19.3 +/- 7.0 to 14.8 +/- 7.6, and mean volume voided per void increased from 92.3 +/- 52.8 to 165.2 +/- 147.7 ml. For patients with retention the mean volume per catheterization decreased from 379.9 +/- 183.8 to 109.2 +/- 184.3 ml, and the mean number of catheterizations decreased from 5.3 +/- 2.8 to 1.9 +/- 2.8. All changes were statistically significant (p <0.001). No life threatening or irreversible adverse events occurred. In 102 patients 279 device or therapy related adverse events were observed. At 5 years after implantation 68% of patients with urge incontinence, 56% with urgency frequency and 71% with retention had successful outcomes. CONCLUSIONS: This long-term study demonstrates that InterStim therapy is safe and effective for restoring voiding in appropriately selected cases refractory to other forms of treatment. PMID- 17869299 TI - Transcutaneous mechanical nerve stimulation using perineal vibration: a novel method for the treatment of female stress urinary incontinence. AB - PURPOSE: We defined basic guidelines for transcutaneous mechanical nerve stimulation in modifying pelvic floor responses in women and determined the efficacy of transcutaneous mechanical nerve stimulation in treating stress urinary incontinence. MATERIALS AND METHODS: Perineal and clitoral transcutaneous mechanical nerve stimulation was performed in healthy volunteers while measuring changes in peak urethral pressure to determine optimal vibration amplitude and site of stimulation. Perineal transcutaneous mechanical nerve stimulation was then performed weekly for 6 weeks in a cohort of women with stress urinary incontinence (33). Reduction in incontinence episodes and pad use on voiding diary were compared from baseline to 6 weeks. Global efficacy was determined at 6 weeks and 3 months after the completion of the program. RESULTS: In healthy subjects a vibration amplitude of 2.0 mm resulted in the highest urethral pressure increase. Although the increase with perineal transcutaneous mechanical nerve stimulation was lower than that seen with clitoral stimulation (80 vs 115 cm H(2)O), perineal transcutaneous mechanical nerve stimulation was more acceptable to the patient and resulted in a better subjective response. Urethral pressure increases with transcutaneous mechanical nerve stimulation at either site were greater than with voluntary contraction (60 cm H(2)O). After 6 weeks of transcutaneous mechanical nerve stimulation in the subjects with stress urinary incontinence, there was a significant reduction in daily incontinence episodes (2.6 +/- 1.1 vs 0.5 +/- 1.1, paired t test p <0.001) and pad use (3.5 +/- 0.9 vs 0.6 +/- 1.3, paired t test p <0.001). At 6 weeks the cure rate (no incontinence episodes) was 73%, with durability through 3 months with 67% still reporting persistent resolution. CONCLUSIONS: Perineal transcutaneous mechanical nerve stimulation has promise as a noninvasive and well tolerated method of treating stress urinary incontinence. PMID- 17869300 TI - Laparoscopic pyeloplasty: a prospective randomized comparison between the transperitoneal approach and retroperitoneoscopy. AB - PURPOSE: A prospective randomized study was performed to compare the results of laparoscopic dismembered pyeloplasty using transperitoneal and retroperitoneal approaches. MATERIALS AND METHODS: A total of 40 patients with primary ureteropelvic junction obstruction were included in the study. The patients were prospectively randomized between transperitoneal (20 patients, group 1) and retroperitoneal (20 patients, group 2) laparoscopic Anderson-Hynes pyeloplasty. All the patients were assessed preoperatively by excretory urography, diuretic isotope renography and computerized tomography angiography. The patients were followed at 3 and 6 months postoperatively, and then every 6 months. Evaluation was performed by excretory urography and diuretic renography. Both approaches were compared regarding operative time, morbidity, hospital stay, convalescence and functional outcome. The preoperative demographic data of the patients and radiological and operative findings were statistically correlated to the operative time. RESULTS: The preoperative data of both groups were comparable. All the procedures were successfully completed with laparoscopy. Mean operative times were 149 and 189 minutes for the transperitoneal approach and retroperitoneoscopy, respectively (p = 0.02). In groups 1 and 2 there were complications in 3 and 5 patients, respectively. Morbidity, hospital stay, convalescence and success rate had no significant differences between the groups. None of the patient parameters apart from the approach had a significant impact on operative time. CONCLUSIONS: Laparoscopic dismembered Anderson-Hynes pyeloplasty has a satisfactory functional outcome and low morbidity regardless of the approach. Nevertheless, with early experience retroperitoneoscopy is associated with a longer operative time. PMID- 17869301 TI - Buccal mucosa graft urethroplasty for anterior urethral stricture repair: evaluation of the impact of stricture location and lichen sclerosus on surgical outcome. AB - PURPOSE: We report our experience with buccal mucosa grafts for anterior urethral strictures. We compared outcomes in the pendulous and bulbar urethra as well as the impact of lichen sclerosus on success. MATERIALS AND METHODS: A total of 53 men underwent buccal mucosa graft urethroplasty from 1997 to 2004 for strictures of all etiologies, including lichen sclerosis in 13. Of the patients 46 underwent 1-stage repair and 7 with full-thickness circumferential disease underwent multistage repair. For 1-stage repair strictures were limited to the bulb in 33 cases and they involved the pendulous urethra in 13. A dorsal onlay was used in 24 cases and a ventral onlay was used in 22. For multistage urethroplasty 2 strictures were in the bulbar urethra and 5 were in the pendulous urethra. Success was defined as no postoperative procedures or complications. RESULTS: The success rate of all urethroplasties was 81% (43 of 53 cases) at a mean followup of 52 months. For bulbar vs pendulous urethroplasty the success rate was 86% (30 of 35 cases) vs 72% (13 of 18, p = 0.23). For 1-stage urethroplasty by graft location success was achieved in 20 of 24 cases (83%) for dorsal onlay vs 17 of 22 (77%) for ventral onlay (p = 0.61), in 18 of 21 (86%) for bulbar-dorsal onlay, in 10 of 12 (83%) for bulbar-ventral onlay, in 2 of 3 (66%) for pendulous-dorsal onlay and in 7 of 10 (70%) for pendulous-ventral onlay. For multistage urethroplasty success was achieved in 2 of 2 cases (100%) for bulbar repair vs 4 of 5 (80%) for pendulous repair. In the 13 patients with lichen sclerosus success was achieved in 4 of 8 (50%) with 1-stage repair vs 4 of 5 (80%) with multistage repair (p = 0.28). Complications developed in 10 of 53 cases (19%), including fistula in 1, urinary tract infection in 1 and stricture in 8 that required treatment, including dilation in 3, internal urethrotomy in 4 and perineal urethrostomy in 1. Five of these 8 recurrent strictures (63%) developed in patients with lichen sclerosus, including 4 in urethras in which 1-stage repair was done for lichen sclerosus. There were no donor site complications, postoperative erectile dysfunction or chordee. CONCLUSIONS: A buccal mucosa graft placed dorsally or ventrally remains an excellent graft material in the bulbar and pendulous urethra. When lichen sclerosus is present, careful consideration should be given to complete excision of the diseased urethra with multistage repair vs accepting a higher rate of stricture recurrence with 1-stage repair. PMID- 17869302 TI - Urethral reconstruction for traumatic posterior urethral disruption: outcomes of a 25-year experience. AB - PURPOSE: Management of posterior urethral disruption due to pelvic trauma can be quite challenging and is the subject of ongoing controversy. This study presents an update of the University of California, San Francisco experience with delayed anastomotic posterior urethroplasty for management of these injuries. MATERIALS AND METHODS: Since 1979 all patients undergoing posterior urethroplasty by a single surgeon at University of California, San Francisco and its affiliated hospitals have been entered prospectively into a patient registry. For this cohort descriptive statistics were calculated and recurrence was analyzed with the Kaplan-Meier method. Success was defined as no recurrence (by symptoms and/or retrograde urethrogram) or a mild recurrence managed successfully with a single internal urethrotomy. RESULTS: A total of 134 male patients were analyzed with a mean of 32.9 and a median of 12 months followup. Mean patient age at surgery was 34.8 years. Of the patients 35% had undergone at least 1 prior procedure for stricture including prior urethroplasty in 16%. In addition, 22% required partial pubectomy and 4% a combined abdominal-perineal approach with total pubectomy. Of patients with a closed bladder neck on urethrography 34% vs 7% of those with an open bladder neck required pubectomy (p <0.001). Stricture length tended to be longer in pubectomy cases (mean 3.2 vs 2.1 cm by urethrography, p = 0.055). Of the patients 14% experienced recurrent stricture at a mean of 12 months, 42% of whom were treated successfully with a single urethrotomy. The overall success rate allowing 1 direct vision internal urethrotomy was 93%. CONCLUSIONS: Anastomotic urethroplasty offers excellent long-term results to patients with posterior urethral trauma and stricture disease even after multiple prior procedures. PMID- 17869303 TI - Robotic reconstruction of the upper urinary tract. AB - PURPOSE: Reconstructive surgery of the upper urinary tract can be complicated. During the last 2 decades minimally invasive techniques have emerged as viable options for these complex procedures. We reviewed our experience with robotic surgery for upper urinary tract reconstruction. MATERIALS AND METHODS: Between May 2002 and December 2006, a single surgeon performed certain robotic reconstructions on the upper urinary tract in 26 males and 37 females (65 renal units), including dismembered pyeloplasty, dismembered pyeloplasty with stone extraction, ureteroureterostomy, ureterolysis with omental wrap, ureterocalicostomy, ureteral reimplantation and upper pole nephroureterectomy. We compared demographic, preoperative, intraoperative and postoperative data on patients undergoing these various procedures. RESULTS: Across all cases mean blood loss was 125 cc, mean operative time was 244.8 minutes and mean length of stay was 2.8 days. The rate of radiographic and symptomatic improvement was 97.3% and 100%, respectively. We observed 2 major complications during a mean followup of 18.7 months. CONCLUSIONS: Our data illustrate that robotics can be successfully and safely used for virtually any type of upper urinary tract reconstruction. Robotic techniques are a viable option for upper urinary tract reconstruction. PMID- 17869304 TI - Ureteroscopic removal of mildly migrated stents using local anesthesia only. AB - PURPOSE: In the outpatient office setting we evaluated the feasibility and efficacy of ureteroscopic removal of upward migrated ureteral stents using local or no anesthesia. MATERIALS AND METHODS: Prospectively 37 patients with mild upward stent migration underwent ureteroscopic stent removal under local or no anesthesia. Stent migration was always below the pelvic brim. It was diagnosed by plain x-ray of the kidneys, ureters and bladder, and flexible cystoscopy. Semirigid ureteroscopy was performed in the office outpatient setting. After each procedure patients graded the discomfort and/or pain level experienced by completing 2 separate 5-scale visual analog pain scores, including 1 for flexible cystoscopy and 1 for the ureteroscopic procedure. Pain scores were compared between the 2 procedures. RESULTS: Stent removal was successful in 34 of 37 patients (91.9%). Successful procedures were never interrupted due to pain intolerance. No complications occurred. The mean visual analog pain score for ureteroscopic stent removal was 1.73 and it was similar in men and women (p = 0.199). The mean visual analog pain score for flexible cystoscopy was 1.27. This procedure was significantly more painful in men than in women (p = 0.018). Ureteroscopic stent removal was more painful than flexible cystoscopy overall and in women (each p <0.01) but not in men (p = 0.3). All patients were discharged home within 1 hour after the procedure and no patient required hospital admission or a new hospital visit. CONCLUSIONS: Ureteroscopic removal of a migrated stent using local anesthesia is effective, safe and tolerable in select patients. Preventing the complications and costs associated with general or spinal anesthesia makes this option appealing to patients and it should be offered when possible. PMID- 17869305 TI - Ethnic differences in relative risk of idiopathic calcium nephrolithiasis in North America. AB - PURPOSE: Data on susceptibility to kidney stone disease are sparse in individuals of nonEuropean ancestry residing in North America. We determined the relative risk of calcium nephrolithiasis among people of different ethnic backgrounds living in the same geographic region. MATERIALS AND METHODS: Using a cross sectional design 1,128 consecutive patients with idiopathic calcium nephrolithiasis 18 to 50 years old were recruited from a population based Kidney Stone Center in Toronto. Age and gender adjusted odds ratios and 95% confidence intervals were calculated by logistic regression using the 2001 Canada Census population data. RESULTS: Compared to Europeans the relative risk of calcium nephrolithiasis was significantly higher in individuals of Arabic (OR 3.8, 2.7 5.2), West Indian (OR 2.5, 1.8-3.4), West Asian (OR 2.4, 1.7-3.4) and Latin American (OR 1.7, 1.2-2.4) origin, and significantly lower in those of East Asian (OR 0.4, 0.3-0.5) and African (OR 0.7, 0.5-0.9) background. Several ethnic groups had kidney stone risk factors that were significantly different from those of the European group including higher urinary uric acid, urea excretion and estimated protein intake, and lower urinary citrate, potassium, magnesium and phosphate excretion. However, none was consistent with the variation in relative risk of stone disease overall. CONCLUSIONS: The propensity for the development of calcium nephrolithiasis differed markedly among ethnic groups in North America. While environmental factors could not be completely ruled out, this variability may reflect the influence of genetic susceptibility because there was no dominant environmental factor to account for the differences in relative risk of stone disease. PMID- 17869306 TI - Mohs micrographic surgery for penile cancer: management and long-term followup. AB - PURPOSE: Mohs micrographic surgery is efficacious for the primary treatment and local recurrence control of nongenital and cutaneous squamous and basal cell cancers. The efficacy of this procedure for squamous cell carcinoma of the penis was reviewed. MATERIALS AND METHODS: We retrospectively reviewed the charts of all patients treated with Mohs micrographic surgery for penile cancer at our institution from 1988 to 2006. RESULTS: We identified 33 patients who underwent a total of 41 Mohs procedures. Average +/- SD lesion size was 509 +/- 699 mm(2). An average of 2.6 +/- 1.4 stages were done using Mohs micrographic surgery. Five procedures were terminated with positive margins, including 3 due to urethral involvement and 2 due to defect size. Of the tumors 26 were stage Tis, 4 were T1, 7 were T2 and 4 were T3. A total of 13 defects were reconstructed by primary repair or granulation, 4 were reconstructed by skin grafts and 25 were reconstructed by tissue flaps and urethroplasty. Followup data were available on 25 patients at a mean of 58 +/- 63 months. Eight patients (32%) had recurrence, which was managed by repeat Mohs micrographic surgery in 7 and by penectomy in 1. There were 2 cases of tumor progression, including 1 from T1 to T3 disease (meatal involvement) and 1 from T1 to inguinal lymph node involvement. Two patients died, of whom 1 had no evidence of penile cancer and 1 had metastatic disease. CONCLUSIONS: Mohs micrographic surgery for low stage penile cancer results in a relatively high local recurrence rate. However, with repeat procedures and vigilant followup cancer specific and overall survival rates are excellent and progression rates are low. PMID- 17869307 TI - Vascular targeted photodynamic therapy with palladium-bacteriopheophorbide photosensitizer for recurrent prostate cancer following definitive radiation therapy: assessment of safety and treatment response. AB - PURPOSE: Tookad is a novel intravascular photosensitizer. When activated by 763 nm light, it destroys tumors by damaging their blood supply. It then clears rapidly from the circulatory system. To our knowledge we report the first application of Tookad vascular targeted photodynamic therapy in humans. We assessed the safety, pharmacokinetics and preliminary treatment response as a salvage procedure after external beam radiation therapy. MATERIALS AND METHODS: Patients received escalating drug doses of 0.1 to 2 mg/kg at a fixed light dose of 100 J/cm or escalated light doses of 230 and 360 J/cm at the 2 mg/kg dose. Four optical fibers were placed transperineally in the prostate, including 2 for light delivery and 2 for light dosimetry. Treatment response was assessed primarily by hypovascular lesion formation on contrast enhanced magnetic resonance imaging and transrectal ultrasound guided biopsies targeting areas of lesion formation and secondarily by serum prostate specific antigen changes. RESULTS: Tookad vascular targeted photodynamic therapy was technically feasible. The plasma drug concentration was negligible by 2 hours after infusion. In the drug escalation arm 3 of 6 patients responded, as seen on magnetic resonance imaging, including 1 at 1 mg/kg and 2 at 2 mg/kg. The light dose escalation demonstrated an increasing volume of effect with 2 of 3 patients in the first light escalation cohort responding and all 6 responding at the highest light dose with lesions encompassing up to 70% of the peripheral zone. There were no serious adverse events, and continence and potency were maintained. CONCLUSIONS: Tookad vascular targeted photodynamic therapy salvage therapy is safe and well tolerated. Lesion formation is strongly drug and light dose dependent. Early histological and magnetic resonance imaging responses highlight the clinical potential of Tookad vascular targeted photodynamic therapy to manage post external beam radiation therapy recurrence. PMID- 17869308 TI - Urologic cancer--when is less more? PMID- 17869309 TI - Effects of anethole and structural analogues on the contractility of rat isolated aorta: Involvement of voltage-dependent Ca2+-channels. AB - Anethole is a naturally occurring aromatic oxidant, present in a variety of medicinal plant extracts, which is commonly used by the food and beverage industry. Despite its widespread occurrence and commercial use, there is currently little information regarding effects of this compound on the vasculature. Therefore the actions of anethole on the contractility of rat isolated aorta were compared with those of eugenol, and their respective isomeric forms, estragole and isoeugenol. In aortic rings precontracted with phenylephrine (PE; 1 microM), anethole (10(-6) M-10(-4) M) induced contraction in preparations possessing an intact endothelium, but not in endothelium-denuded tissues. At higher concentrations (10(-3) M-10(-2) M), anethole-induced concentration dependent and complete relaxation of all precontracted preparations, irrespective of whether the endothelium was intact or not, an action shared by eugenol, estragole and isoeugenol. The contractile and relaxant effects of anethole in PE precontracted preparations were not altered by L-NAME (10 microM) or indomethacin (10 microM), indicating that neither nitric oxide nor prostaglandins were involved in these actions. The mixed profile of effects was not confined to PE mediated contraction, since similar responses were obtained to anethole when tissues were precontracted with 25 mM KCl. Anethole and estragole (10(-6)-10(-4) M), but not eugenol or isoeugenol, increased the basal tonus of endothelium denuded aortic rings, an action that was abolished by VDCC blockers nifedipine (1 microM) and diltiazem (1 microM), or by withdrawal of extracellular Ca(2+). Our data suggest complex effects of anethole on isolated blood vessels, inducing contraction at lower doses, mediated via opening of voltage-dependent Ca(2+) channels, and relaxant effects at higher concentrations that are shared by structural analogues. PMID- 17869310 TI - Acid-induced modulation of airway basal tone and contractility: role of acid sensing ion channels (ASICs) and TRPV1 receptor. AB - The role of extracellular acidosis in inflammatory airway diseases is not well known. One consequence of tissue acidification is the stimulation of sensory nerves via the polymodal H(+)-gated transmembrane channels ASICs and TRPV1 receptor. The present study investigated the effect of acidosis on airway basal tone and responsiveness in the guinea pig. Acidosis (pH 6.8, 10 min, 37 degrees C) significantly decreased the basal tone of tracheal rings (p<0.01 vs. paired control). Moreover, pH fall raised the maximal contraction of tracheal rings to acetylcholine (p<0.05 vs. paired control). The pH-induced relaxation of airway basal tone was inhibited by pretreatments with ASIC1a or ASIC3/ASIC2a inhibitors (0.5 mM ibuprofen, 0.1 mM gadolinium), nitric oxide synthase inhibitor (1 mM L NAME), and guanylate cyclase inhibitor (1 microM ODQ). In contrast, the pH induced relaxation of airway basal tone was not modified by epithelium removal or pretreatments with a TRPV1 antagonist (1 microM capsazepine), a combination of NK(1,2,3) receptor antagonists (0.1 microM each), a blocker of voltage-sensitive Na(+) channels (1 microM tetrodotoxin), a cyclooxygenase inhibitor with no activity on ASICs (1 microM indomethacin) or ASIC3 and ASIC3/ASIC2b inhibitors (10 nM diclofenac, 1 microM aspirin). Furthermore, acid-induced hyperresponsiveness to acetylcholine was inhibited by epithelium removal, capsazepine, NK(1,2,3) receptor antagonists, tetrodotoxin, amiloride, ibuprofen and diclofenac. In summary, the initial pH-induced airway relaxation seems to be independent of sensory nerves, suggesting a regulation of airway basal tone mediated by smooth muscle ASICs. Conversely, the pH-induced hyperresponsiveness involves sensory nerves-dependent ASICs and TRPV1, and an unknown epithelial component in response to acidosis. PMID- 17869311 TI - Expression of striatal adenosine and dopamine receptors in mice deficient in the p50 subunit of NF-kappaB. AB - The striatal dopamine D2 receptor (D2R) and adenosine A2A receptor (A2AAR) exhibit mutually antagonistic effects through physical interactions and by differential modulation of post-receptor signaling pathways. The expression of the A2AAR and the D2R is differentially regulated by nuclear factor-kappaB (NF kappaB). In this report, we determined the role of NF-kappaB in regulation of these receptors by comparing mice deficient in the NF-kappaB p50 subunit (p50 KO) with genetically intact B6129PF2/J (F2) mice. Quantification of adenosine receptor (AR) subtypes in mouse striatum by real time PCR, immunocytochemistry and radioligand binding assays showed more A2AAR but less A1AR in p50 KO mice as compared with F2 mice. Striata from p50 KO mice also had less D2R mRNA and [(3)H] methylspiperone binding than did striata from F2 mice. G(alphaolf) and G(alphas) proteins, which are transducers of A2AAR signals, were also present at a higher level in striata from the p50 KO versus F2 mice. In contrast, the G(alphai1) protein, which transduces signals from the A1AR and D2R, was significantly reduced in striata from p50 KO mice. Behaviorally, p50 KO mice exhibited increased locomotor activity relative to that of F2 mice after caffeine ingestion. These data are consistent with a role for the NF-kappaB in the regulation of A1AR, A2AAR, D2R and possibly their coupling G proteins in the striatum. Dysregulation of these receptors in the striata of p50 KO mice might sensitize these animals to locomotor stimulatory action of caffeine. PMID- 17869312 TI - Implication of cytosolic phospholipase A2 (cPLA2) in the regulation of human synoviocyte NADPH oxidase (Nox2) activity. AB - NADPH oxidase Nox2 is involved in the production of superoxide by rheumatoid synovial cells, constitutively and after pro-inflammatory cytokine treatment. The aims of the study were to evaluate the capacity of these cells to produce the superoxide anion in response to arachidonic acid (AA), and to study the involvement of cytosolic phospholipase A(2) (cPLA(2)) in the cytokine regulation of Nox2. Superoxide production was quantified in synovial cells obtained from six patients with rheumatoid arthritis (RA) and six with osteoarthritis (OA), stimulated with (i) AA, and (ii) PLA(2) inhibitors prior to IL-1beta or TNF-alpha treatment. Total cellular AA concentrations and PLA(2) activity were measured; effects of cytokines and NADPH oxidase inhibitors on the AA-activatable proton channel opening were also studied. Our results demonstrated that AA enhanced superoxide production in RA and OA cells; this production was significantly inhibited by iodonium diphenyl and apocynin. cPLA(2) inhibitors inhibited both IL 1beta and TNF-alpha-induced superoxide production in RA and OA cells. Basal PLA(2) activity was significantly more important in RA cells than in OA cells; PLA(2) activity was increased in IL-1beta and TNF-alpha pre-treated RA cells, and cPLA(2) inhibitors inhibited this activity. Opening of the AA-activatable proton channel was amplified when RA cells were pre-treated with both IL-1beta and TNF alpha, and iodonium diphenyl and apocynin inhibited these cytokine effects. We concluded that AA is an important cofactor for synovial NADPH oxidase activity. Despite their direct effects on p47-phox phosphorylation, cytokines can also regulate the Nox2 activity though the AA-activatable associated H(+) channel. PMID- 17869313 TI - A Petri net approach to the study of persistence in chemical reaction networks. AB - Persistence is the property, for differential equations in R(n), that solutions starting in the positive orthant do not approach the boundary of the orthant. For chemical reactions and population models, this translates into the non-extinction property: provided that every species is present at the start of the reaction, no species will tend to be eliminated in the course of the reaction. This paper provides checkable conditions for persistence of chemical species in reaction networks, using concepts and tools from Petri net theory, and verifies these conditions on various systems which arise in the modeling of cell signaling pathways. PMID- 17869314 TI - Theory of Mind disruption and recruitment of the right hemisphere during narrative comprehension in autism. AB - The intersection of Theory of Mind (ToM) processing and complex narrative comprehension in high functioning autism was examined by comparing cortical activation during the reading of passages that required inferences based on either intentions, emotional states, or physical causality. Right hemisphere activation was substantially greater for all sentences in the autism group than in a matched control group suggesting decreased LH capacity in autism resulting in a spillover of processing to RH homologs. Moreover, the ToM network was disrupted. The autism group showed similar activation for all inference types in the right temporo-parietal component of the ToM network whereas the control participants selectively activated this network only when appropriate. The autism group had lower functional connectivity within the ToM network and also between the ToM and a left hemisphere language network. Furthermore, the within-network functional connectivity in autism was correlated with the size of the anterior portion of the corpus callosum. PMID- 17869315 TI - Cytotoxic and apoptosis-inducing effect of ent-15-oxo-kaur-16-en-19-oic acid, a derivative of grandiflorolic acid from Espeletia schultzii. AB - ent-Kaurenic acid and many natural derivatives of this diterpene are known to have interesting biological properties. ent-15-Oxo-kaur-16-en-19-oic acid can be easily obtained from grandiflorolic acid which was first isolated from Espeletia grandiflora. The present work describes the proapoptotic effect of ent-15-oxo kaur-16-en-19-oic acid on the human prostate carcinoma epithelial cell line PC-3 as evidenced by the changes in the expression level of proteins associated with the execution and regulation of apoptosis. Cell viability was affected upon exposure to the compound, the IC(50) were determined as 3.7 microg/ml, which is 4 times lower than that corresponding to a primary cell culture of fibroblasts (14.8 microg/mL). Through Western blot analysis, active forms of caspace-3 associated with the specific proteolysis of Poly(ADP-ribose) polymerase (PARP) were detected. Reduced levels of the antiapoptotic protein Bcl-2, as well as the appearance of internucleosomal DNA fragmentation, were also demonstrated. Thus, ent-15-oxo-kaur-16-en-19-oic acid may be a promising lead compound for new chemopreventive strategies, alone or in combination with traditional chemotherapy agents to overcome drug resistance in tumoral cells. PMID- 17869316 TI - Influence of food polyphenols on aryl hydrocarbon receptor-signaling pathway estimated by in vitro bioassay. AB - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxic and biological actions of many aromatic environmental pollutants such as dioxins. We investigated AhR activation by some vegetable constituents, including flavonoids, tannins, and related polyphenols, using an AhR-based in vitro bioassay for dioxins. Among the compounds tested, marked AhR activation was exhibited by isoflavones such as daidzein, resveratrol (a stilbene) structure, some flavanones such as naringenin, and flavones such as baicalein. On the other hand, some flavones such as apigenin, flavonols such as quercetin, and anthraquinones such as emodin, showed notable inhibitory effects on the in vitro activation of AhR induced by the dioxin [2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)]. In addition, AhR-mediated interactions between AhR and some plant extracts, including those from vegetables, fruits, herbs, and teas, were tested by using the AhR-based bioassay. Of the samples tested, some leafy green vegetables, citrus fruits, and herbs that contain food polyphenolics showed AhR-based interactions at high concentrations. On the basis of these finding, we discuss the implications of polyphenols on the AhR-signaling pathway. PMID- 17869317 TI - Anticancer and antiproliferative activity of natural brassinosteroids. AB - Brassinosteroids (BRs) are steroid plant hormones that are essential for many plant growth and developmental processes, including cell expansion, vascular differentiation and stress responses. Up to now the inhibitory effects of BRs on cell division of mammalian cells are unknown. To determine basic anticancer structure-activity relationships of natural BRs on human cells, several normal and cancer cell lines have been used. Several of the tested BRs were found to have high cytotoxic activity. Therefore, in our next series of experiments, we tested the effects of the most promising and readily available BR analogues with interesting anticancer properties, 28-homocastasterone (1) and 24-epibrassinolide (2), on the viability, proliferation, and cycling of hormone sensitive/insensitive (MCF-7/MDA-MB-468) breast and (LNCaP/DU-145) prostate cancer cell lines to determine whether the discovered cytotoxic activity of BRs could be, at least partially, related to brassinosteroid-nuclear receptor interactions. Both BRs inhibited cell growth in a dose-dependent manner in the cancer cell lines. Flow cytometry analysis showed that BR treatment arrested MCF 7, MDA-MB-468 and LNCaP cells in G(1) phase of the cell cycle and induced apoptosis in MDA-MB-468, LNCaP, and slightly in the DU-145 cells. Our results provide the first evidence that natural BRs can inhibit the growth, at micromolar concentrations, of several human cancer cell lines without affecting the growth of normal cells. Therefore, these plant hormones are promising leads for potential anticancer drugs. PMID- 17869318 TI - Multiple attractors in a discrete competition model. AB - The existence of multiple attractors in a competition model implies that the question of coexistence vs. extinction can depend on initial conditions. A discrete stage-structured model of two competing species is derived from a well tested single-species model of insect populations, and is shown to exhibit multiple attractors for parameter values similar to those used in laboratory experiments which demonstrated chaos in population dynamics. The corresponding basins of attraction are investigated and shown to have very complex structures, and the initial stage structure of the populations is shown to have a significant impact on final outcomes. PMID- 17869319 TI - Flexural vibration analyses of piezoelectric ceramic tubes with mass loads in ultrasonic actuators. AB - Based on Timoshenko beam model, a theoretical model of radially polarized piezoelectric ceramic tubes is investigated. In the model, the piezoelectric effects are considered, and the shear correction factor is introduced which reveals effects of the size of the cross-section and Poisson's ratio. Based on the model, the particular attentions are devoted to effects of the boundary conditions at two ends on flexural resonance frequencies of the piezoelectric ceramic tubes. Changing the sizes of the tubes and the mass loads at both free ends, the variations of the flexural resonance frequencies of free-free piezoelectric ceramic tubes are calculated theoretically. Besides, the flexural resonance frequencies of the piezoelectric ceramic tube cantilevers with mass loads at one free end are also investigated theoretically. To verify accuracy of the theoretical mode, the flexural resonance frequencies for different lengths of the piezoelectric ceramic tubes and different loaded masses are measured experimentally. The theoretical results agree well with the experimental measurement, which demonstrates that the model is accurate for analyzing the flexural resonance frequencies of the piezoelectric ceramic tubes with mass loads. PMID- 17869320 TI - Identification of a 17-nucleotide splicing enhancer in HPV-16 L1 that counteracts the effect of multiple hnRNP A1-binding splicing silencers. AB - Human papillomavirus type 16 (HPV-16) infections can in rare cases persist and cause lesions that may progress to cervical cancer. Cells in the lesions are not permissive for virus production, nor are cervical cancer cells. The intracellular environment is such that it prevents production of the highly immunogenic, viral structural proteins L1 and L2. One may speculate that inhibition of L1 and L2 expression is a prerequisite for persistence and cancer progression. We have therefore investigated how expression of HPV-16 L1 is regulated. We found that the only splice site in the HPV-16 late region, which is used to produce L1 mRNAs, is under control of a splicing enhancer located in the 17 nucleotides immediately downstream of the splice site. However, the function of this enhancer in cervical cancer cells is largely overshadowed by multiple splicing silencers in the late region which bind to hnRNP A1. High levels of hnRNP A1 therefore inhibit HPV-16 L1 expression. Immunohistological analysis of cervical epithelia revealed that hnRNP A1 is expressed primarily in the lower layers of the epithelium. hnRNP A1 is undetectable in terminally differentiated cells that can express HPV-16 late genes, which supports the conclusion that high levels of hnRNP A1 inhibit HPV-16 L1 expression. PMID- 17869321 TI - Inverse modeling of human contrast response. AB - Mathematical singularities found in the Signal Detection Theory (SDT) based analysis of the 2-Alternative-Forced-Choice (2AFC) method [Katkov, M., Tsodyks, M., & Sagi, D. (2006a). Analysis of two-alternative force-choice Signal Detection Theory model. Journal of Mathematical Psychology, 50, 411-420; Katkov, M., Tsodyks, M., & Sagi, D. (2006b). Singularities in the inverse modeling of 2AFC contrast discrimination data. Vision Research, 46, 256-266; Katkov, M., Tsodyks, M., & Sagi, D. (2007). Singularities explained: Response to Klein. Vision Research, doi:10.1016/j.visres.2006.10.030] imply that contrast discrimination data obtained with the 2AFC method cannot always be used to reliably estimate the parameters of the underlying model (internal response and noise functions) with a reasonable number of trials. Here we bypass this problem with the Identification Task (IT) where observers identify one of N contrasts. We have found that identification data varies significantly between experimental sessions. Stable estimates using individual session data showed Contrast Response Functions (CRF) with high gain in the low contrast regime and low gain in the high contrast regime. Noise Amplitudes (NA) followed a decreasing function of contrast at low contrast levels, and were practically constant above some contrast level. The transition between these two regimes corresponded approximately to the position of the dipper in the Threshold versus Contrast (TvC) curves that were computed using the estimated parameters and independently measured using 2AFC. PMID- 17869322 TI - Contamination of soils with organochlorine pesticides in urban parks in Beijing, China. AB - Urban parks are an integral component of healthy urban living. Since they are frequently visited, an understanding of the environmental quality of these urban facilities is crucial. Here, a study was conducted on the contamination of soils in the parks of Beijing. Organochlorine pesticides (OCPs), which have the potential to cause endocrine disturbances, were considered study objectives. Hexachlorocyclohexanes (HCHs) were found at concentrations of 0.2490-197.0 ng g( 1) and dichlorodiphenyltrichloroethanes (DDTs) were found at concentrations of 5.942-1039 ng g(-1) in the soils investigated. The preliminary pollution assessment indicated that DDTs have caused high pollution levels in the soils of some parks. Analysis of the sources of contamination showed that HCHs in the soils were derived from an old mixed source of technical HCHs and lindane and that DDTs, which were suspected to have recent application to the soils at some sites, were derived mainly from a mixture of technical DDTs and dicofol containing DDT impurities. An independent sample t-test proved that pesticides containing DDTs had been used in large amounts in the soils of parks before 1983 (p<0.05) and that the levels of DDTs in the soils of parks administered by the Beijing municipal government were significantly higher than the levels in those administered by the district government (p<0.05). However, the main difference in this situation needs to be further studied. This study suggested that open spaces like urban parks were not as sound as was expected and that there was potential for exposure of visitors/workers in the parks to organochlorine pesticides. PMID- 17869323 TI - Adsorption characteristics of carbonaceous adsorbents for organic pollutants in a model incineration exhaust gas. AB - Adsorption characteristics of carbonaceous adsorbents were examined using 1,2,3,4 tetrachlorobenzene, naphthalene and 2,4,6-tribromophenol as adsorbates. The breakthrough and equilibrium adsorption characteristics were evaluated using laboratory-scale adsorption test equipment. A micropore volume of diameter less than 2 nm is the most important factor governing the adsorption capacity of all adsorbates. A kinetic analysis was performed and the adsorption behavior of the adsorbates was analyzed. Diffusion within porous particles controls the adsorption rate in this system, and the diffusion process is a function of pore diffusion. The operating conditions in working incineration facility adsorbers were reviewed and the breakthrough time of these adsorbents in actual adsorbers was estimated using the mass transfer zone method. Information on the optimal operating conditions of adsorbers was derived from the adsorption breakthrough characteristics. PMID- 17869324 TI - Nitrate reduction by fluoride green rust modified with copper. AB - Nitrate reduction by the fluoride form of green rust modified with copper (GR F(Cu)) was investigated using a batch reactor system. The extent of nitrate reduction was measured by measuring the increase in concentration of ammonia, which is the final product of nitrate reduction by GR. This approach was required, because nitrate could be removed from solution by ion exchange without reduction. The rate of ammonium production was investigated over the range of pH 7.8-11. The fastest reaction was achieved at pH 9 when GR was present at a concentration of 0.083M as Fe(II) and 1mM of Cu(II) was added. The rate at pH 9 was enhanced by a factor of 2.5 compared to that at pH 7.8 by comparing the time elapsed to transform all nitrate to ammonium. Kinetics of nitrate reduction by GR F at pH 7.8 were affected by the concentration of Cu(II) added. The rate constants for ammonium production increased from 0.012 to 1.52h(-1) as Cu(II) additions increased from 0 to 2.5mM, but the reaction rate at 5mM was slightly decreased to 1.25h(-1). The mechanism of enhanced rates of nitrate reduction by addition of Cu(II) could not be fully determined in this study. However, XRD results showed that magnetite was produced in the reaction of Cu(II) and GR-F and SEM shows the production of nano-size particles which were not fully identified in this study. In addition, the concentration of Fe(II) in GR was observed to linearly decrease with concentration of Cu(II) added. PMID- 17869325 TI - Distribution of detoxifying genes polymorphism in Maharastrian population of central India. AB - The present study is aimed at evaluating the genotype frequency of detoxifying genes such as GSTM1, GSTT1 and NQO1 in Maharastrian population of central India. The study revealed about 64.6% of GSTM1-positive and 35.4% GSTM1-null population. GSTT1-positive genotype was found to be 87.5% and GSTT1-null showed 12.5%. The NQO1 genotype of Maharastrian population showed 52.3% of C/C, 42.48% C/T and 5.18% T/T. The NQO1 of this population does not deviate from the expected Hardy Weinberg equilibrium. The genotype frequencies GSTM1 and GSTT1 of the population when compared with other ethnic groups of Asia and Caucasians show distinct nature of Maharastrian population from other Asian and Caucasian population. PMID- 17869326 TI - Effects of long-term erythropoietin therapy on fibrinolytic system in haemodialyzed patients. AB - INTRODUCTION: Recombinant human erythropoietin (rHuEPO) is the cornerstone of anaemia therapy in uraemic patients however the effects of this hormone on fibrinolytic system are difficult to interpret. MATERIALS AND METHODS: Assessment of fibrinolytic parameters: tissue-type plasminogen activator (tPA) antigen, urokinase-type plasminogen activator (uPA) and its soluble receptor (suPAR), plasminogen activator inhibitor 1 (PAI-1) and plasmin/antiplasmin (PAP) complexes were performed in haemodialyzed (HD) patients without rHuEPO therapy: Group I (n=8, Hg<10 g/dl); Group II (n=12, Hg>10 g/dl); and in HD patients treated with rHuEPO for more than 6 months (Group III, n=10) or for more than 12 months (Group IV, n=9) in relation to the healthy controls. RESULTS: Patients of Group I had the significantly lower haematological parameters than those of Groups II, III and IV. All the fibrinolytic parameters studied, except PAI-1, were significantly higher in HD patients without rHuEPO therapy when compared to the controls. There were no significant differences in fibrinolytic system between the Groups I and II. Erythropoietin therapy resulted in progressive decrease in antigenic tPA levels, which reach normal range values after 6 months rHuEPO administration. uPA and PAP concentrations were also decreased and reached normal values after 12 months of rHuEPO therapy. In these patients a significant decrease in uPAR levels was also observed. Therapy with rHuEPO did not alter PAI-1 concentrations in HD patients. CONCLUSIONS: These results suggest that long-term rHuEPO therapy can correct fibrinolytic parameters in patients undergoing regular HD irrespective from haemoglobin levels and in the absence of concomitant iron supplementation. PMID- 17869327 TI - Modulation of endothelial cell thrombomodulin by PPAR ligands--variation according to environment. AB - INTRODUCTION: Thrombomodulin (TM) is an important anti-coagulant protein that is down-regulated on endothelial cells overlying atherosclerotic plaques. We investigated the effects of the peroxisome proliferator-activated receptor (PPAR) ligands, fenofibrate and rosiglitazone, on the expression of TM ex vivo by advanced carotid atheromas, and in vitro by endothelial cells. METHODS: Adjacent carotid atheroma biopsies were incubated in vehicle control or PPAR ligand in explant culture for 4 days. Human aortic endothelial cells were incubated with PPAR ligands in vitro. TM expression was measured by Western blotting and flow cytometry. TM activity was assessed by generation of activated protein C. RESULTS: The PPAR-alpha activator, fenofibrate, up-regulated total TM expression within carotid explants by 1.7-fold (P<0.001) with no effect on activity. Rosiglitazone treatment had no effect on protein levels but reduced activity by 73% of the control (P<0.05). We noted disparate effects of PPAR ligands in atheroma samples from different patients and postulated that the response of endothelial cells to medication was influenced by the atheromatous environment. Incubation of human aortic endothelial cells with fenofibrate alone led to a dose dependent increase in TM expression (P<0.05), however, in the presence of oxidized LDL a dose-dependent reduction in TM expression was induced by fenofibrate (P<0.05). CONCLUSIONS: The ability of fenofibrate to increase endothelial cell and carotid atheroma TM protein expression suggests a potential therapeutic role for this medication. The response to PPAR ligands likely varies depending on the exact constituents of individual atherosclerotic plaques, such as the relative amount of oxidized LDL. PMID- 17869328 TI - Protein Z levels and anti-protein Z antibodies in patients with arterial and venous thrombosis. AB - INTRODUCTION: The thrombotic risk associated with protein Z (PZ) deficiency is unclear. Anti-protein Z (anti-PZ) has been described as a risk factor in unexplained embryo demise. The aim of our study was to evaluate a possible PZ deficiency and presence of anti-PZ antibodies on thrombotic diseases. MATERIAL AND METHODS: We performed a case-control study on 114 patients with preexisting arterial or venous thrombosis (50 and 64, respectively). Thrombosis was studied based on etiology (creating factor risk subgroups) and on specific thrombotic disease. RESULTS: PZ levels of patients were significantly lower compared to controls (1709+-761.3 ng/mL vs. 2437+-964.7 ng/mL P=0.001). The high arterial risk factor subgroup showed the lowest PZ level (1267.5+-609 ng/mL) whereas the rest of arterial and venous etiological subgroups presented similar PZ levels. Patients with peripheral artery disease had the lowest PZ level (1022+-966 ng/mL). The rest of arterial and venous thrombotic diseases presented similar PZ levels. A significant increased risk for arterial and venous thrombosis for the lowest (<1685 ng/mL) quartile of PZ has been founded (OR:52, P=0.001 and OR:18, P=0.007, respectively). Anti-PZ antibodies were negative in the majority of patients, although mean anti-PZ IgG antibody levels in the arterial thrombosis group were significantly higher compared to venous thrombosis and control groups (P=0.05 and P=0.005, respectively). CONCLUSIONS: The results suggest that both arterial and venous thrombotic events are related to low PZ levels and that low PZ concentrations are associated with thrombosis in our study. In arterial thrombosis our findings strengthen previous studies that related low PZ levels to atherosclerotic disease. Anti-PZ antibodies do not seem to play a potent role in thrombosis. PMID- 17869329 TI - Mechanisms underlying adaptation of action potential duration by pacing rate in rat myocytes. AB - Heart rate is an essential determinant of cardiac performance. In rat ventricular myocytes, a sudden increase in rate yields to a prolongation of the action potential duration (APD). The mechanism underlying this prolongation is controversial: it has been proposed that the longer APD is due to either: (1) a decrease in K+ currents only or (2) an increase in Ca2+ current only. The aim of this study was to quantitatively investigate the contribution of Ca2+ and K+ currents in the adaptation of APD to pacing rate. Simulation using a mathematical model of ventricular rat cardiac cell model [Pandit, S.V., Clark, R.B., Giles, W.R., Demir, S.S., 2001. A mathematical model of action potential heterogeneity in adult rat left ventricular myocytes. Biophys. J. 81, 3029-3051] predicted a role in the prolongation of APD for K+ currents only. In patch clamp experiments, increasing the pacing rate leads to a significant increase in APD in both control and detubulated myocytes, although it was more marked in control than detubulated myocytes. Supporting the model prediction, we observed that increasing stimulation frequency leads to a decrease in K+ currents in voltage clamped rat ventricular myocytes (square and action potential waveforms), and to a similar extent in both cell types. We have also observed that frequency-dependent facilitation of Ca2+ current occurred in control cells but not in detubulated cells (square and action potential waveforms). From these experiments, we calculated that the relative contribution of Ca2+ and K+ currents to the longer APD following an increase in pacing rate is approximately 65% and approximately 35%, respectively. Therefore, in contrast to the model prediction, Ca2+ current has a significant role in the adaptation of APD to pacing rate. Finally, we have introduced a simplistic modification to the Pandit's model to account for the frequency-dependent facilitation of Ca2+ current. PMID- 17869330 TI - Treatment of pulmonary recurrences in patients with endometrial cancer. AB - OBJECTIVE: To assess the treatment and outcome of patients with endometrial cancer following isolated pulmonary relapse. METHODS: Between 1984 and 1996, 82 of 1109 patients undergoing surgery for primary endometrial cancer experienced a primary pulmonary recurrence, 28 of which were solitary. Median follow up of censored patients after isolated pulmonary recurrence was 159 months. RESULTS: Grade 1/2 disease, pulmonary nodule size <2 cm, and the presence of estrogen receptors (ER) were significant (p<0.05) predictors of improved disease specific survival (DSS) in the 28 patients with an isolated lung recurrence. Median DSS for the 11 patients with grade 1/2 tumors and pulmonary nodules measuring 60 dB (A) and < or =60 dB (A), respectively. Children's blood pressure was measured with mercury sphygmomanometer. Heart rate was counted by radial artery palpitation for 1 min. The prevalence of children with hypertensive values of blood pressure was 3.96% (13 children, including 8 boys and 5 girls) with higher prevalence in children from noisy residences (5.70%), compared to children from quiet residences (1.48%). The difference was borderline significant (p=0.054). Systolic pressure was significantly higher (5 mm Hg on average) among children from noisy residences and kindergartens, compared to children from both quiet environments (p<0.01). Heart rate was significantly higher (2 beats/min on average) in children from noisy residences, compared to children from quiet residences (p<0.05). Multiple regression, after allowing for possible confounders, showed a significant correlation between noise exposure and children's systolic pressure (B=1.056; p=0.009). PMID- 17869341 TI - A synergistic effect of a combined bivalent DNA-protein anti-HIV-1 vaccine containing multiple T- and B-cell epitopes of HIV-1 proteins. AB - Immunogenic properties of the combined vaccine CombiHIVvac, comprising polyepitope HIV-1 immunogens, one being the artificial polyepitope protein TBI, containing the T- and B-cell epitopes from Env and Gag proteins, and the DNA vaccine construct pcDNA-TCI coding for the artificial protein TCI, carrying over 80 T-cell epitopes (both CD4+ CTL and CD8+ Th) from Env, Gag, Pol, and Nef proteins, are studied in this work. The data reported demonstrate clearly that a combination of two B- and T-cell immunogens (TBI and TCI) in one construct results in a synergistic increase in the antibody response to both TBI protein and the proteins from HIV-1 lysate. The level of antibodies induced by immunization with the constructs containing either immunogen alone (TBI protein or the plasmid pcDNA-TCI) was significantly lower as compared to that induced by the combined vaccine. The analysis performed suggests that the presence of CD4+ T helper epitopes, which can be presented by MHC class II, in the protein TCI may be the main reason underlying the increased synthesis of antibodies to TBI protein due to a CD4-mediated stimulation of B-cell proliferation and differentiation. PMID- 17869342 TI - T cell allorecognition and MHC restriction--A case of Jekyll and Hyde? AB - A great paradox in cellular immunology is how T cell allorecognition exists at high frequencies (up to 10%) despite the stringent requirements of discriminating 'self' from 'non-self' imposed by MHC restriction. Thus, in tissue transplantation, a substantial proportion of the recipient's T cells will have the ability to recognize the graft and instigate an immune response against the transplanted tissue, ultimately resulting in graft rejection--a manifestation of T cell alloreactivity. Transplantation of human organs and lymphoid cells as treatment for otherwise life-threatening diseases has become a more routine medical procedure making this problem of great importance. Immunologists have gained important insights into the mechanisms of T cell alloreactivity from cytotoxic T cell assays, affinity-avidity studies, and crystal structures of peptide-MHC (pMHC) molecules and T cell receptors (TCRs) both alone and in complex. Despite the clinical significance of alloreactivity, the crystal structure of an alloreactive human TCR in complex with both cognate pMHC and an allogeneic pMHC complex has yet to be determined. This review highlights some of the important findings from studies characterizing the way in which alloreactive T cell receptors and pMHC molecules interact in an attempt to resolve this great irony of the cellular immune response. PMID- 17869343 TI - Prevalence of primary angle-closure disease in an urban south Indian population and comparison with a rural population. The Chennai Glaucoma Study. AB - OBJECTIVE: To determine the prevalence of primary angle-closure glaucoma (PACG), primary angle closure (PAC), and PAC suspect (PACS) in an urban population, and to compare prevalence and associated risk factors with a rural population. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Four thousand eight hundred subjects 40 years or older were selected from Chennai city using multistage random cluster sampling. INTERVENTION: All subjects had a complete ophthalmic examination that included logarithm of the minimum angle of resolution visual acuity, applanation tonometry, gonioscopy, grading of lens opacities, dilated fundus examination, optic disc photography, and visual fields. MAIN OUTCOME MEASURES: Glaucoma was diagnosed using the International Society of Geographical and Epidemiological Ophthalmology classification. RESULTS: Three thousand eight hundred fifty (80.2%) responded; 34 subjects (17 female, 17 male) had PACG (0.88%; 95% confidence interval [CI], 0.60-1.16). The mean intraocular pressure (IOP) was 26.0+/-14.9 mmHg. Five subjects (14.7%) had been previously diagnosed to have glaucoma, 1 of whom had undergone glaucoma surgery and 2 of whom had been diagnosed to have open-angle glaucoma. Two subjects (5.9%) were bilaterally and 3 subjects (8.8%) were unilaterally blind. One hundred six subjects (2.75%; 95% CI, 2.01-3.49) were diagnosed to have PAC (62 female, 44 male). Thirty-nine subjects (36.8%) had presenting IOP > 24 mmHg, 83 (78.3%) had peripheral anterior synechiae, and 16 (15.1%) had both. Two hundred seventy-eight subjects (7.24%; 95% CI, 6.38-8.02) had PACS (183 female, 95 male). Prevalences of PACG and PACS were similar in the urban and rural populations. Primary angle closure prevalence was higher in the urban population (P<0.0001). Primary angle closure and PACG were positively associated with increasing age and IOP in both populations and were more common in rural women (odds ratio [OR], 4.3; 95% CI, 2.2-8.3). Association with hyperopia was seen only in the urban population (OR, 2.0; 95% CI, 1.4-2.8). CONCLUSIONS: Prevalences of PACG and PACS were similar in the rural and urban populations; PAC was more common in the urban population. In both groups, the disease was asymptomatic. Poor detection rates were probably due to lack of gonioscopy as a routine part of an eye examination. PMID- 17869344 TI - P300 of auditory event related potentials in occupational chronic solvent encephalopathy. AB - This retrospective study characterized the P300 component of the auditory event related potential (ERP) and assessed its diagnostic value in occupational chronic solvent encephalopathy (CSE). The P300 was recorded on 86 CSE patients by the classical oddball paradigm. In addition to the laboratory's reference values, we used an age and education matched control group that consisted of 104 blue-collar workers with no known occupational solvent exposure. The association of P300 values with solvent exposure indices, major depression, alcohol consumption, and neuropsychological parameters was studied. The P300 amplitude was lower in CSE patients (mean 7.5 microV; S.D. 3.6) compared to laboratory controls (mean 11.8 microV; S.D. 4.1; F(1,167)=24.4; p<0.001, 95% CI -4.4 to -1.8) and to matched controls (mean 9.0 microV; S.D. 4.0; p=0.007, 95% CI -2.6 to -0.4). The P300 latency was longer in the CSE patients (mean 358 ms; S.D. 28) compared to laboratory controls (mean 339 ms; S.D. 19, F(1,167)=7.6, p=0.006, 95% CI 3.12 18.7) but did not differ from matched controls (mean 358 ms; S.D. 22; p=0.947, 95% CI -7.4 to 6.9). The solvent exposure indices, major depression, or alcohol consumption did not associate with the P300 values. The P300 amplitude correlated positively with the Digit Symbol test. All the amplitude values in the patient group and in the matched control group were classified as normal (i.e. age corrected mean+/-2.5S.D.) against the laboratory's reference values. Thirty percent of the latencies in the CSE patient group and 26% in the matched control group were classified as abnormal. At group level, the decreased P300 amplitudes in CSE patients may reflect solvent-related pathophysiology. However, the P300 measured with the classical oddball paradigm does not seem to be sensitive at individual level or useful in clinical practice. PMID- 17869345 TI - The course of nitric oxide and superoxide dismutase during treatment of bipolar depressive episode. AB - BACKGROUND AND AIMS: Studies have already pointed out a possible pathophysiological role of oxidative and antioxidative molecules in bipolar disorder. We aimed to evaluate the activity and levels of antioxidant superoxide dismutase (SOD), and oxidant nitric oxide (NO), in bipolar I depressive episode (BD-DE) patients in a prospective design. METHOD: 30 BD-DE patients, diagnosed according to DSM IV, and 30 healthy volunteer controls were included. The serum levels of NO and SOD have been studied when admitted to hospital (1st) and on the 30th days. Clinical outcome was measured by Hamilton Depression Scale (HAM-D). The patients were allowed to have their treatments. One patient was dropped out due to insufficient sampling. RESULTS: As in the previous studies, NO 1st day levels were significantly higher in patients and SOD 1st day activity was significantly low (p<0.01). NO levels significantly decreased (p<0.01) and normalized, as SOD activity significantly increased but did not reach to the controls' levels (p<0.01) on the 30th day. CONCLUSION: Despite normalized NO levels, persistent low SOD activity might point out an oxidative imbalance in BD DE. Chronic low SOD activity may be associated with incapacity of coping with oxidative stress. This research connotes the probable oxidative imbalance in BD DE and discusses that phenomenon within the continuum of the disease state. PMID- 17869346 TI - The association between maternal depression and frequent non-routine visits to the infant's doctor--a cohort study. AB - BACKGROUND: Perinatal depression is common, but women typically do not seek help for it. We studied its association with frequent non-routine physician visits, which may be a form of help-seeking behaviour. METHODS: A prospective cohort study of women in their 34th to 38th week of pregnancy at the outpatient obstetrics clinic at a Singapore tertiary hospital was done. Screening was done using the Edinburgh Postnatal Depression Scale and diagnosis of major or minor depressive disorder was made using the SCID-IV. At 6 to 12 months' post-partum, women were screened and interviewed again for depression and asked to report the frequencies with which they had brought their infants to the doctor on non routine visits in the preceding 6 weeks. Four hundred and seventy-one of the 559 patients recruited before delivery were re-interviewed. RESULTS: After adjusting for confounders, women who had brought their infants for three or more non routine visits to the infant's doctor had a significantly higher prevalence of depression (32.6%) than those with fewer visits (13.6%) (OR 2.87, 95% CI 1.41 to 5.85, p=0.004). The relative risk reduction for women who did not bring their infants for frequent non-routine visits was 0.583 (95% CI 0.44 to 0.73, p=0.002). They were also more likely to have poorer perceived emotional support from their families. LIMITATIONS: These included use of self-reported doctor visits, and relatively high educational levels of the participants. CONCLUSIONS: Doctors should have a high index of suspicion for enquiring about depression and emotional support in mothers who bring their infants for frequent non-routine visits. PMID- 17869347 TI - Dissociative experiences on ice--peritraumatic and trait dissociation during the cold pressor test. AB - The present study investigated the relationship between trait dissociation and peritraumatic dissociation during acute painful stimulation. In a sample of 70 undergraduate students, peritraumatic dissociation was induced by means of a cold pressor test, which basically consists of participants holding an arm in ice water for as long as possible. Results indicate that heightened trait dissociation scores were related to shorter durations that participants could sustain the task. However, trait dissociation was not associated with increases in acute dissociative symptoms (i.e., peritraumatic dissociation). These findings are in sharp contrast to the defensive function ascribed to both types of dissociation and also the commonly held assumption that peritraumatic and trait dissociation are intimately linked. PMID- 17869348 TI - CpG-ODN enhances mammary gland defense during mastitis induced by Escherichia coli infection in goats. AB - Seven healthy native goats in early lactation, weighing 30-40 kg, were used in this study. The right mammary gland of the seven does were infused with CpG-ODN at a dosage of 100 microg kg(-1) body weight on the day 5 postpartum (PP). The left glands were used as controls and infused with sterile phosphate-buffered saline (PBS). On day 8 PP, the same dosage of CpG-ODN or PBS was again infused. On day 9 PP, the mammary glands (both right and left) of the seven does were infused with 6 x 10(6) colony-forming units (CFU) Escherichia coli and, at 0, 8, 16, 24, 48 and 72 h postinfection (PI), milk samples were collected from all glands. Goats were euthanized at 72 h PI and the mammary tissue harvested. Infusion with 6 x 10(6)CFU ml(-1)E. coli induced acute mastitis. Histopathological evaluations showed that polymorphonuclear neutrophils (PMNs) were still present in alveoli at 72 h PI, but PMNs in the CpG-ODN-treated glands has disappeared. Bacteria counts in milk peaked at 16 h PI and CpG-ODN induced a significant decrease in viable bacteria from 16 h PI until the end of the experiment. This study showed that CpG-ODN promoted the expression of its specific receptor (TLR-9 mRNA) in mammary tissue, stimulated IL-6 production, reduced bacteria counts in milk, attenuated the impact of inflammation mediators on cells and significantly shortened the inflammation course. These results suggest that the CpG-ODN improved mammary gland defense and, thereby, had a beneficial effects against mastitis caused by E. coli infection in goats. PMID- 17869349 TI - Antibodies against Epstein-Barr virus and herpesvirus type 6 are associated with the early phases of multiple sclerosis. PMID- 17869350 TI - Pediatric cochlear implantation in Taiwan: long-term communication outcomes. AB - OBJECTIVES/HYPOTHESIS: Cochlear implantation is an established method of auditory rehabilitation for severely and profoundly hearing impaired individuals. Although numerous studies have examined communication outcomes in pediatric cochlear implant (CI) recipients, data concerning the benefits of cochlear implantation in children who speak Mandarin Chinese are lacking. This study examined communication outcomes in 29 Mandarin-speaking children implanted at Chung Gung Memorial Hospital. DESIGN: A prospective between-groups design was used to compare communication outcomes as a function of age at time of implantation. METHODS: Children in the Younger group were implanted before 3 years of age, whereas children in the Older group were implanted after 3 years of age. Outcome measures assessed auditory thresholds, speech perception, speech intelligibility, receptive and expressive language skills, communication barriers, and communication mode. Correlation analysis was used to examine the relationship between communication outcome and age at implantation. RESULTS: Children in the Younger group demonstrated a significant level of difference on Mandarin vowels, consonants, tones, and open-set speech perception compared with the children in the Older group. Between-group differences were also shown on receptive and expressive language skills. But, no significant differences were noted on speech intelligibility or in self-ratings of communication barriers. A larger proportion of children in the Younger group used oral communication and were educated in mainstream classrooms. Communication mode change of the Younger group reached a significant level after cochlear implant. Speech perception performance was negatively correlated with age at implantation as well as chronological age. Mandarin-speaking children can obtain substantial communication benefits from cochlear implantation, with earlier implantation yielding superior results. PMID- 17869351 TI - Rapid determination of viral RNA sequences in mosquitoes collected in the field. AB - A method for rapid determination of viral RNA sequences (RDV) was applied to homogenates of Aedes aegypti collected in Thailand in an area in which dengue fever (dengue hemorrhagic fever) is endemic, using the mosquito cell line C6/36. Nucleic acid sequences of dengue virus type 4 and cell fusing agent virus were detected. This RDV method has the potential to become a standard method for detection of both known and newly emerging, unknown mosquito-borne viruses. PMID- 17869352 TI - Optical fiber immunosensor for the detection of IgG antibody to Rift Valley fever virus in humans. AB - This paper describes the development and evaluation of an optical fiber immunosensor (OFIS) for the detection of IgG antibody to Rift Valley fever virus (RVFV) in humans. The OFIS was based on a sandwich enzyme-linked immunosorbent assay (S-ELISA) format, whereby gamma-irradiated RVFV and control antigens were immobilized on the optical fiber surface coated with a mouse anti-RVFV antibody. Data sets derived from field-collected sera in Africa (n=242) were dichotomized according to the results of a virus neutralization test. Compared to standard colorimetric S-ELISA, the OFIS technique was more sensitive in detecting smaller quantity of specific IgG to RVFV in human sera. At cut-off value selected at a 95% accuracy level by the two-graph receiver operating characteristic analysis, the OFIS diagnostic sensitivity was 97.22% and diagnostic specificity 98.86%. Our results demonstrate that the OFIS technology reported here is highly accurate, simple to perform and has the potential to be used in a portable format. PMID- 17869353 TI - Dileucine signal-dependent and AP-1-independent targeting of a lysosomal glycoprotein in Trypanosoma brucei. AB - Sorting of trans-membrane proteins destined for the lysosome is achieved by selective inclusion into post-Golgi transport vesicles. In higher eukaryotes sorting may be mediated by a peptidic motif, principally acidic clusters and tyrosine- or dileucine-based cytoplasmic signals or by inclusion of mannose-6 phosphate (M6P) into the N-glycans of lysosomal proteins. In African trypanosomes a major lysosomal trans-membrane protein is CB-1/p67. The cytoplasmic domain of p67 lacks tyrosine and lysine, but does contain a canonical dileucine sequence embedded within an acidic region. AP-1, -3 and -4 adaptin complexes, which recognise tyrosine- and dileucine-sorting signals, are encoded by the trypanosome genome, but the genes for M6P-receptors or activities required to produce M6P are absent, suggesting that lysosomal delivery of p67 is most likely adaptin mediated. By construction of p67 reporter constructs we show that the dileucine signal is necessary and sufficient for efficient lysosomal delivery of a trans membrane protein in bloodstream stage trypanosomes. However, this targeting does not require AP-1, as knockdown of the trypanosome gamma-adaptin subunit by RNAi has no detectable effect on the location or maturation of p67. These data suggest that p67 is targeted to the lysosome by dileucine-dependent but AP-1-independent mechanisms. PMID- 17869354 TI - Paroxysmal atrioventricular block and right coronary artery stenosis without acute myocardial infarction. AB - Paroxysmal atrioventricular block is an ill-defined entity, previously described in sporadic cases in association with vasovagal reaction, coronary angiography and distal conduction disease. The occurrence of atrioventricular block in acute inferior wall myocardial infarction is related to the presence of an important right coronary artery that is occluded, the recanalisation of this vessel leads often to rapid regression of the block that is no longer pejorative. We present a case of paroxysmal atrioventricular block at monitor in a 44-year-old Italian man with right coronary artery stenosis and without acute myocardial infarction. Error in computer electrocardiogram interpretation was excluded. Coronary angiography revealed significant right coronary artery stenosis. Percutaneous transluminal coronary angioplasty with implantation of stent was successfully performed. PMID- 17869355 TI - "Lots of clots": multiple thromboemboli including a huge paradoxical embolus in a 29-year old man. AB - Paradoxical embolism occurs when a venous thrombus passes into the arterial circulation, most commonly through an intracardiac shunt. This phenomenon has been associated with catastrophic outcomes such as stroke and ischemic limb. We report the case of a 29-year old man with multiple thromboemboli including a deep venous thrombus, bilateral pulmonary emboli, and a paradoxical embolus into his left subclavian artery. We postulate the underlying predisposition and sequence of events that may have resulted in these multiple blood clots and report on his successful surgical outcome. PMID- 17869356 TI - Percutaneous treatment of aorto-pulmonary window in a one year old child. PMID- 17869357 TI - Left cor triatriatum: a rare potential cause of total anomalous pulmonary vein connection obstruction. PMID- 17869358 TI - Delayed papillary muscle rupture following percutaneous mitral balloon valvotomy. PMID- 17869359 TI - Acute myocardial infarction due to right coronary artery occlusion in dextrocardia. PMID- 17869360 TI - Fighting cancer with plant-expressed pharmaceuticals. AB - Cancer is one of the most prevalent diseases worldwide, which explains why biological therapies for cancer are forecast to make up 35% of total recombinant pharmaceuticals by 2010. Because of the high demand for cancer drugs, the need to lower production costs and the constraints of present production technologies for recombinant pharmaceuticals (such as the difficulties involved in culturing bacteria, yeast and mammalian cells), attention has recently been focused on recombinant expression of pharmaceutical anti-cancer proteins in plants. This review aims to provide an update on the most recent publications about anti cancer recombinant pharmaceuticals expressed in plants, as well as on the relevant technical issues, potential and prospects of this emerging production system. PMID- 17869361 TI - Safety assessment of dairy microorganisms: coagulase-negative staphylococci. AB - The genus Staphylococcus is made up of 36 validated species which contain strains that are pathogenic, saprophytic, or used as starter cultures for the food industry. Staphylococci species used in cheese-making are novobiocin-resistant, coagulase-negative and are not usually identified at species level by routine laboratories. A bibliographic survey was conducted to assess safety status of CNS used in fermented dairy foods. Commercial kits based on phenotypic discrimination can't reliably identify these species because of the variable expression of some phenotypic traits. Several molecular targets, including 16S rRNA, hsp60, tuf, SodA and rpoB genes can be used for identifying species of the Staphylococcus genus. No coagulase-negative staphylococci isolated from milk or dairy products has ever been involved in a case of food poisoning or human pathology following ingestion of dairy products. Nevertheless, a few case of nosocomial infection caused by some species (S. caprae, S. capitis, S. sciuri) have been reported in patients with depressed immune systems or who have undergone long severe hospital treatments, or in the presence of an indwelling catheter or foreign materials such as cardiac prostheses. They may therefore be regarded as exceptional opportunistic pathogens in certain clinical situations. PMID- 17869362 TI - Evaluation of the Weibull and log normal distribution functions as survival models of Escherichia coli under isothermal and non isothermal conditions. AB - Published survival curves of Escherichia coli in two growth media, with and without the presence of salt, at various temperatures and in a Greek eggplant salad having various levels of essential oil, all had a characteristic downward concavity when plotted on semi logarithmic coordinates. Some also exhibited what appeared as a 'shoulder' of considerable length. Regardless of whether a shoulder was noticed, the survival pattern could be considered as a manifestation of an underlying unimodal distribution of the cells' death times. Mathematically, the data could be described equally well by the Weibull and log normal distribution functions, which had similar modes, means, standard deviations and coefficients of skewness. When plotted in their probability density function (PDF) form, the curves also appeared very similar visually. This enabled us to quantify and compare the effect of temperature or essential oil concentration on the organism's survival in terms of these temporal distributions' characteristics. Increased lethality was generally expressed in a shorter mean and mode, a smaller standard deviation and increased overall symmetry as judged by the distributions' degree of skewness. The 'shoulder', as expected, simply indicated that the distribution's standard deviation was much smaller than its mode. Rate models based on the two distribution functions could be used to predict non isothermal survival patterns. They were derived on the assumption that the momentary inactivation rate is the isothermal rate at the momentary temperature at a time that corresponds to the momentary survival ratio. In this application, however, the Weibullian model with a fixed power was not only simpler and more convenient mathematically than the one based on the log normal distribution, but it also provided more accurate estimates of the dynamic inactivation patterns. PMID- 17869363 TI - Spontaneous Lactobacillus delbrueckii phage-resistant mutants with acquired bile tolerance. AB - Three commercial phage-sensitive strains of Lactobacillus delbrueckii (strains Ab(1), YSD V and Ib(3)) and four spontaneous phage-resistant mutants (strains A(7), A(17), V(2) and I(39)) isolated from them, all with a probiotic potential previously demonstrated were studied for their tolerance of bile salts (ox gall). Minimal Inhibitory Concentrations (MICs) ranged from 0.30% to 0.35% (w/v) of ox gall. These strains were exposed to gradually increasing concentrations of ox gall with the aim of isolating bile resistant derivatives. Stable derivatives able to tolerate up to 0.9% of ox gall were obtained from L. delbrueckii Ab(1), as well as from its spontaneous phage-resistant mutants A(7) and A(17). Random Amplified Polymorphic DNA (RAPD-PCR) analysis revealed a strong genetic homology between the ox gall-tolerant derivatives and their respective non-adapted original strains. These derivatives maintained, in general, the phage resistance phenotype of the non-adapted strains, with only one exception (phage-resistant mutant A(7)). After progressive ox gall adaptation, the phage-resistant mutant A(7) also exhibited progressive reversion of the phage resistance phenotype. The derivative with the highest ox gall-acquired tolerance (A(7)(0.9)) became sensitive to the phage, but derivatives with low (A(7)(0.3)) and intermediate (A(7)(0.6)) ox gall-acquired tolerance retained phage resistance. The technological properties of ox gall derivatives were comparable to those of their respective parent strains. However, the cells of the former were smaller than those of the original strains. Finally, the tolerant derivatives grew faster in the presence of ox gall than the parent strains. Our results demonstrated that it was possible to obtain, by a natural selection strategy, probiotic strains with acquired ox gall-tolerance from three (L. delbrueckii Ab(1) and their phage resistant mutants A(7) and A(17)) of seven tested strains. Since such derivatives keep both phage resistance and other useful technological properties, they could be used for production of functional foods. PMID- 17869364 TI - Safety assessment of dairy microorganisms: Geotrichum candidum. AB - Geotrichum candidum is a ubiquitous filamentous yeast-like fungus commonly isolated from soil, air, water, milk, silage, plant tissues, digestive tract in humans and other mammals. This species is widely used as adjunct culture in the maturation of cheese. The genus Geotrichum is composed of 18 species. A recent taxonomic revision concluded that the old Galactomyces geotrichum/G. candidum complex contained four separate species of which Galactomyces candidus sp. nov./G. candidum. M13 primer can be used for identifying species of the Geotrichum genus. Used in combination, RAPD-PCR and RAM-PCR permit strains to be differentiated. The species can be unambiguous differentiated from the two species most frequently described in human pathology: Geotrichum clavatum (reclassified Saprochaete clavata) and Geotrichum capitatum (reclassified Magnusiomyces capitatus/Saprochaete capitata). Sources of exposure are food ingestion--cheese consumption playing a major role--inhalation and contact. A bibliographic survey was conducted to assess corresponding hazards and risks. G. candidum infections (mainly pulmonary or bronchopulmonary, but also cutaneous, oral, disseminates) are very rare: fewer than 100 cases reported between 1842 and 2006. Moreover, cases were not all confirmed by repeated isolations and demonstration of the fungus' presence in tissues, a prerequisite to establish a true diagnosis of geotrichosis. Immunocompromised population was recently shown as a target for opportunistic infection. The most effective treatments include either azole drogs as ketonazole, iconazole and clotrimazole, or polyene antibiotics as amphotericin B, nystatin and pimaricin, or voriconazole amphotericin B association. Less than 1 case/year of disease was possibly caused by G. candidum and it never included dairy products or foodborne infection. The risk of developing an infection due to G. candidum in connection with its technological use and consumption of dairy products is virtually nil. For these reasons, G. candidum should be proposed for QPS status. PMID- 17869365 TI - Human papillomavirus 16 E6, L1, L2 and E2 gene variants in cervical lesion progression. AB - The human papillomavirus (HPV) 16 E6 genome variant 350G has been found to be more prevalent in women with persistent infection and cervical disease progression than the HPV16 E6 prototype 350T. In this study, we examined whether women who progressed to a high-grade lesion, yet were infected with the prototype 350T, showed variants in other HPV genes such as L1, L2 and E2. Although we detected variants within these genes, they could not explain this phenomenon. Indeed they correlated similarly with variant 350G and prototype 350T. These data indicate that polymorphisms in HPV16 E6 rather than in the other analyzed genes play a role in determining the risk for cervical lesion progression and that additional factors are likely to be required as well. PMID- 17869366 TI - A molecular epidemiological study of rabies in Puerto Rico. AB - The mongoose is the principal reservoir for rabies on the island of Puerto Rico. This report describes a molecular epidemiological study of representative rabies viruses recovered from the island in 1997. Two closely related but distinct variants circulating in regionally localised parts of the island were identified. The lack of a monophyletic relationship of these viruses suggests that two independent incursions of rabies onto the island have occurred. Both of these Puerto Rican variants were closely related to a variant, known as the north central skunk strain, currently circulating in North American skunk populations and all are members of the cosmopolitan rabies lineage spread during the colonial period. However, the Puerto Rican viruses are clearly distinct from those presently circulating in mongooses in Cuba and which are epidemiologically closely linked to the Mexican dog rabies virus. This study clearly establishes the distinct origins of the rabies viruses now circulating on these two Caribbean islands. PMID- 17869367 TI - Liberation of doxorubicin from HPMA copolymer conjugate is essential for the induction of cell cycle arrest and nuclear fragmentation in ovarian carcinoma cells. AB - Despite intensive study, the molecular mechanism for cell toxicity of N-(2 hydroxypropyl)methacrylamide (HPMA) copolymer-bound doxorubicin remains unclear. Moreover, the ability of the released drug to accumulate in the nucleus has also been questioned. We have hypothesized that the pattern of cell cycle progression is a useful indicator for the presence of free doxorubicin in the nucleus and its interaction with nuclear DNA. The effects of HPMA copolymer-bound doxorubicin on cell cycle progression were evaluated in this study in cultured human ovarian cancer A2780 cells. We determined that P-GFLG-DOX, but not P-GG-DOX, initiates cell cycle arrest and nuclear fragmentation in the same manner as free DOX, but with a time-delay. Our data indicate that drug release from the conjugate is required for the apoptotic activity associated with the conjugate. PMID- 17869368 TI - [Obesity and knee osteoarthritis]. PMID- 17869369 TI - Thrombocytopenia in chronic liver disease: lessons from transplanted patients. PMID- 17869370 TI - Omega 3 - Omega 6: What is right for the liver? AB - Linoleic and alpha-linolenic acids are the fatty acids designated as "essential" since they are not synthesized by mammalian cells and must be provided in the diet. The recent dietary shift towards the consumption of n-6 (omega-6) at the expense of n-3 (omega-3) polyunsaturated fatty acids (PUFAs) is thought to be a primary cause of many diseases related to the Western diet. The body converts linoleic acid to arachidonic acid and derives eicosapentaenoic acid from alpha linolenic acid. Ideally the effects of these fatty acids and their eicosanoid derivatives are tailored to the specific biological needs of the body. The balance between n-3 and n-6 PUFAs is essential for metabolism and maintenance of the functions of both classes. The availability of n-3 long chain PUFAs plays a major role in regulating both fat accumulation and its elimination by the liver. Derangement of hepatic n-6:n-3 PUFA ratio impacts on the histological pattern of fatty liver through modulation of the amount of intrahepatic lipids. Moreover, the influence of PUFAs and their eicosanoid products on hepatic microcirculation and ischemia/reperfusion injury has been demonstrated in many studies. This concise review article will focus on the role of PUFAs and eicosanoids in hepatic steatosis, microcirculation and ischemia/reperfusion injury. PMID- 17869371 TI - Is exchange transfusion a possible treatment for neonatal hemochromatosis? AB - Neonatal hemochromatosis is a rare congenital disorder of the liver associated to a poor prognosis. Liver transplantation is often required, since no effective medical treatment has been found. Despite mounting evidence of an alloimmune etiology of this condition, exchange transfusion has never been proposed as a specific treatment for neonatal hemochromatosis. Here we describe two siblings affected by neonatal hemochromatosis. The first, a female, died at 18 days of severe coagulopathy and acute renal failure, diagnosed as affected by neonatal hemochromatosis only when the second sibling was suspected as being affected by the same disease. The second child showed a rapidly worsening coagulopathy which was treated with two exchange transfusions, followed by rapid clinical and laboratory improvement, before reaching a definite diagnosis of neonatal hemochromatosis. He is healthy at present after a follow-up of 12 months. Although exchange transfusion has never been considered as treatment for neonatal hemochromatosis, this case suggests that it could be a feasible treatment option for children affected by this disease, as for other alloimmune conditions. PMID- 17869372 TI - Granulocyte colony-stimulating factor impairs liver regeneration in mice through the up-regulation of interleukin-1beta. AB - BACKGROUND/AIMS: Stem cell induction via granulocyte colony-stimulating factor (G CSF) administration is utilized in the treatment of various diseases. Therefore, we examined the effect of G-CSF administration to a liver fibrosis model induced by dimethylnitrosamine (DMN). METHODS: ICR mice were subcutaneously injected with either G-CSF (150microg/kg) or saline at days 0, 3, 7 and 10. Subacute liver injury was established by intraperitoneal injection of DMN (10mg/kg) on three consecutive days of each week. RESULTS: G-CSF administration significantly decreased the survival rate of mice treated with DMN. There was no difference in the degree of liver injury or fibrosis between either group of mice. However, assessment by proliferating cell nuclear antigen (PCNA) revealed that the G-CSF treated mice experienced a greater degree of inhibition of liver cell proliferation than the control mice. Interleukin-1beta (IL-1beta) mRNA expression increased in the livers of G-CSF-treated mice. PCNA staining and analysis of cell cycle-related proteins also revealed that passive immunization with anti-IL-1beta neutralizing antibody improved the impaired hepatocellular regeneration and resulted in an improved survival rate of mice treated with G-CSF and DMN. CONCLUSIONS: G-CSF administration suppressed liver cell proliferation through the up-regulation of IL-1beta expression in DMN-induced liver injury. PMID- 17869373 TI - Assessment of low-grade hepatic encephalopathy: a critical analysis. AB - BACKGROUND/AIMS: The value of paper-pencil tests and West-Haven-criteria for assessment of low-grade hepatic encephalopathy under conditions of a randomized, double-blind, placebo-controlled, clinical trial was evaluated in a cohort of 217 cirrhotics. METHODS: Patients were graded at least twice clinically for severity of hepatic encephalopathy and tested concomitantly with a recommended psychometric test battery. RESULTS: Re-evaluation of the study documentation showed that at study entry 33% and during the study even 50% of the patients were wrongly allocated to minimal or overt hepatic encephalopathy. Despite the participating physicians' training, 31% of the number-connection-tests-A, 20% of the number-connection-tests-B and 28% of the line-tracing-test were in retrospect considered invalid by an independent psychologist. Neither the Portosystemic Encephalopathy-Syndrome (PSE) test nor the Psychometric-Hepatic-Encephalopathy Sum (PHES)-score reliably picked up clinical improvement in the individual patient. Although these test scores could statistically differentiate between patients with minimal and overt hepatic encephalopathy, the clinical classification of individual patients into one of the groups will have a high rate of error. The PHES-Score was less balanced than the score derived from the PSE-Syndrome-Test. CONCLUSIONS: Inaccuracies in conducting paper-pencil tests together with the subjectivity and incorrectness of clinical HE-grading question the usefulness of West-Haven-criteria and paper-pencil tests including related scores for quantification of low-grade HE at least in multicenter approaches. PMID- 17869374 TI - A planning tool for two-phase case-control studies. AB - We present a software tool for planning two-phase case-control studies assuming categorical covariates. Two-phase designs, in which validation or complete information data are sampled stratified both on a dichotomous outcome and a covariate from a first-phase study with incomplete data, result in efficient estimates compared to standard designs. Efficiency and power depend on sample size, sampling fractions within each stratum x outcome cell, distributional assumptions and the regression model. Our software, called Two-Phase Planning Tool (or 2P Planning Tool), offers a graphical user interface (GUI) to organize and input the relevant anticipated entities and calculates a normed, expected two phase case-control study. The 2P Planning Tool is especially helpful in selecting a stratification. The data are output into an Excel-sheet, which in turn can be read into a standard statistics package to perform "experimental" power calculations. Its use is illustrated by an example from epidemiology. Software for analyzing logistic two-phase studies is also provided. PMID- 17869375 TI - Interferon-based therapy of hepatitis C. AB - In 2007, the world celebrated the 50th anniversary of the discovery of interferon (IFN). The first clinical trial of recombinant IFN-alpha in patients with chronic hepatitis C was published in 1986. This article reviews the classification of IFNs, IFN production during viral infections, IFN signaling pathways and the mechanisms of their antiviral and immunomodulatory properties. Hepatitis C virus infection treatment is currently based on the combination of pegylated IFN-alpha and ribavirin. The pegylated IFN-alpha molecules are described, as well as the putative mechanisms of action of ribavirin. Current treatment guidelines are discussed and new results suggesting that the treatment schedule should be tailored to the early virological response during therapy are presented. Finally, insights into new hepatitis C drug developments are given. PMID- 17869376 TI - Transgenic animal models of neurodegenerative diseases and their application to treatment development. AB - Neurodegenerative disorders of the aging population affect over 5 million people in the US and Europe alone. The common feature is the progressive accumulation of misfolded proteins with the formation of toxic oligomers. Previous studies show that while in Alzheimer's disease (AD) misfolded amyloid-beta protein accumulates both in the intracellular and extracellular space, in Lewy body disease (LBD), Parkinson's disease (PD), Multiple System Atrophy (MSA), Fronto-Temporal dementia (FTD), prion diseases, amyotrophic lateral sclerosis (ALS) and trinucleotide repeat disorders (TNRD), the aggregated proteins accumulate in the plasma membrane and intracellularly. Protein misfolding and accumulation is the result of an altered balance between protein synthesis, aggregation rate and clearance. Based on these studies, considerable advances have been made in the past years in developing novel experimental models of neurodegenerative disorders. This has been in part driven by the identification of genetic mutations associated with familial forms of these conditions and gene polymorphisms associated with the more common sporadic variants of these diseases. Transgenic and knock out rodents and Drosophila as well as viral vector driven models of Alzheimer's disease (AD), PD, Huntington's disease (HD) and others have been developed, however the focus for this review will be on rodent models of AD, FTD, PD/LBD, and MSA. Promising therapeutic results have been obtained utilizing amyloid precursor protein (APP) transgenic (tg) models of AD to develop therapies including use of inhibitors of the APP-processing enzymes beta- and gamma-secretase as well as vaccine therapies. PMID- 17869377 TI - Advances in the development of new therapeutic agents targeting the NS3-4A serine protease or the NS5B RNA-dependent RNA polymerase of the hepatitis C virus. AB - The HCV NS3 protease and NS5B polymerase play essential roles in the replication of the hepatitis C virus (HCV). Following the successful paradigm established for HIV protease and reverse transcriptase inhibitors, these enzymes have been elected as targets for the development of small molecule HCV inhibitors. By combining the power of high-throughput screening with rational, knowledge-based drug discovery, a number of competitive inhibitors of the NS3 protease as well as nucleoside and non-nucleoside inhibitors of the NS5B polymerase have been identified and some have now entered clinical trials. In this article we review recent progress in the discovery and development of small molecule inhibitors of these two essential viral enzymes as they are advancing in the clinic. PMID- 17869378 TI - Anti-cancer PEG-enzymes: 30 years old, but still a current approach. AB - PEGylation (i.e. the covalent link of PEG strands) is a well known technique used to improve pharmaceutical properties of bioactive proteins and peptides. Even in cancer therapy some proteins, in particular enzymes, can find many applications, because of their antiproliferative action or ability to reduce side effects of chemotherapies, but to do so they need to be properly formulated. Unfortunately, formulation alone can not fulfil all the requirements to yield a safe and successful protein preparation for therapeutic applications. In particular, for many proteins fast clearance from the body and potential immunogenicity are severe limitations, which can not be easily overcome without taking into consideration a purposely designed drug delivery system. Among the approaches in the field of drug delivery, PEGylation has so far been the best choice for protein delivery. Here, we describe some examples of PEGylated enzymes useful in antitumoral therapies and the most recent advances in this field. PMID- 17869379 TI - Obestatin and ghrelin in obese and in pregnant women. AB - We identified, through qPCR, receptor mRNA for a number of gut peptides in female human omental fat: the incretins, GIP and GLP-1, the orexigenic peptides PYY-Y1 and -Y2 and ghrelin, and the anorexigenic peptide obestatin. Four cohorts of women were examined: lean controls (BMI<23), obese (BMI>41), obese diabetic and term pregnant women. Human fat expressed receptor mRNAs for all six peptides. Pregnant women expressed roughly three times as much orphan GPR-39 receptor, a proposed obestatin receptor, than other women and less than half as much of the ghrelin receptor (GHSR-1a). An immunoblot probed with a GPR-39 selective antibody yielded a single band corresponding to the correct molecular weight (52 kDa) for the proposed obestatin receptor. Fluorescent immunohistochemistry of human fat employing the same antibody indicated the receptor protein was localized to the adipocyte cell membrane. The concentration of obestatin circulating in blood was measured in the same cohort of women and was significantly lower in obese and obese diabetic women compared to control. PMID- 17869380 TI - Changes of beta-casomorphin content in human milk during lactation. AB - Milk is the best, complete food important for the development and nourishment of a neonate. Except for nutrients, milk contains biologically active opioid peptides derived from beta-casein, named beta-casomorphins (BCMs), which can exert effects in the gastrointestinal tract as well as in the whole body of neonates. The content of beta-casomorphins in human milk during maturation phases has not been studied so far. The aim of this study was to determine the content of beta-casomorphin-5 and -7 in human milk in different phases of lactation. A significantly higher concentration of both beta-casomorphins was found in colostrum than in mature milk. The concentration of beta-casomorphin in milk collected in the second month of lactation was similar to the level obtained in the fourth month of lactation. The content of beta-casomorphins in human milk was observed with the period of lactation. The level of opioid peptides may depend on the function of these peptides in neonate's body and may be associated with the maturation process. PMID- 17869381 TI - NAP protects hippocampal neurons against multiple toxins. AB - The femtomolar-acting protective peptide NAP (NAPVSIPQ), derived from activity dependent neuroprotective protein (ADNP), is broadly neuroprotective in vivo and in vitro in cerebral cortical cultures and a variety of cell lines. In the present study, we have extended previous results and examined the protective potential of NAP in primary rat hippocampal cultures, using microtubule associated protein 2 (MAP2) as a measure for neuroprotection. Results showed that NAP, at femtomolar concentrations, completely protected against oxygen-glucose deprivation, and cyanide poisoning. Furthermore, NAP partially protected against kainic acid excitotoxicity. In summary, we have significantly expanded previous findings in demonstrating here direct neuroprotective effects for NAP on vital hippocampal neurons that are key participants in cognitive function in vivo. PMID- 17869382 TI - Blood-brain barrier: ageing and microvascular disease--systematic review and meta analysis. AB - Cerebral "microvascular" disease occurs in lacunar stroke, leukoaraiosis, vascular dementia and Alzheimer's disease. It may arise from or contribute to insidious damage to the blood-brain barrier (BBB). We systematically reviewed the literature for evidence that BBB permeability is altered in patients with manifestations of cerebral microvascular disease. We found 31 BBB permeability studies (1953 individuals) of normal ageing or cerebral microvascular disease. In healthy humans, increasing age (10 comparisons, controls(C):subjects(S)=357:336) was associated with increased BBB permeability (standardised mean difference (S.M.D.) 1.21, 95% confidence interval (CI) 0.60, 1.81, p<0.01). BBB permeability was increased further in patients with either vascular or Alzheimer's dementia compared with age-matched controls (26 comparisons, C:S=510:547, S.M.D. 0.81, 99% CI 0.37, 1.26, p<0.01); in vascular compared with Alzheimer's dementia (10 comparisons, C:S=291:165, S.M.D. 0.71, 99% CI 0.12, 1.29, p<0.01); and with worsening leukoaraiosis (5 comparisons, C:S=122:88, S.M.D. 0.60, 99% CI 0.30, 0.89, p<0.01). BBB permeability increases with normal ageing and may be an important mechanism in the initiation or worsening of cerebral microvascular disease. Further studies on the role of BBB permeability are urgently needed. PMID- 17869383 TI - Relative contributions of the cerebellar vermis and prefrontal lobe volumes on cognitive function across the adult lifespan. AB - Recent research has revealed significant relationships between the vermian regions of the cerebellum and cognitive functions typically associated with prefrontal lobe function. These relationships are believed to be supported by anatomical connections between the distant brain regions. Recent evidence also suggests that age-related reductions in the posterior vermis are associated with age-related decline in frontal lobe cognitive functions, but these studies did not consider concomitant age-related atrophy of the prefrontal lobes. In the present study we addressed this issue by examining cognitive and structural MRI data obtained from 251 adults ranging in age from 18 to 79. Cognition was examined with a computerized cognitive battery and volumes of the cerebellar vermian regions and the prefrontal lobes were determined using quantitative morphometry. Results of the study revealed that both prefrontal and vermian volumes were smaller in older adults compared to younger adults, and both volumes correlated with cognitive performances in the older individuals. However, after controlling for prefrontal volume, the relationships between cognitive function and vermian volumes were eliminated, whereas prefrontal lobe volume remained significantly related to cognitive function after controlling for vermian volumes. These results suggest that while a reduction in cerebellar vermian volume does not significantly relate to normal age-related cognitive decline, prefrontal volume is significantly related to cognitive aging. Our results are consistent with the frontal aging hypothesis. PMID- 17869385 TI - Basic 3-hydroxypyridin-4-ones: potential antimalarial agents. AB - 3-Hydroxypyridin-4-ones selectively bind iron under biological conditions and one such compound has found application in the treatment of thalassaemia-linked iron overload. Related molecules have also been demonstrated to possess an antimalarial effect at levels which are non-toxic to mammalian cells. In an attempt to improve the efficiency of such molecules we have investigated the effect of introducing basic nitrogen centres into 3-hydroxypyridin-4-ones in an attempt to achieve targeting to lysosomes and other intracellular acidic vacuoles. Several of the compounds reported in this communication possess enhanced antimalarial activity over that of the simple hydroxypyridinone class. PMID- 17869386 TI - Non-nucleoside HIV-1 reverse transcriptase inhibitors. Part 11: structural modulations of diaryltriazines with potent anti-HIV activity. AB - A series of novel 6-naphthyloxy substituted DATA analogues bearing different substituents on the C-6 position of triazine ring were synthesized and evaluated for their in vitro anti-HIV activity in MT-4 cells. The results demonstrated that most of the compounds in this series are potent activity against HIV-1 with moderate to high selectivity. Among these analogues, two compounds exhibited excellent effect in inhibiting HIV-1 replication at nanomolar concentration (for compound 9h: IC(50)=9.3 nM, SI=15,385; for compound 9i: IC(50)=9.4 nM, SI=14,094), which are about 15-fold more active than nevirapine. In addition, several compounds are active against both HIV-1 and HIV-2, whose mechanism may be different from typical NNRTIs. PMID- 17869384 TI - Differential effects of aging and Alzheimer's disease on medial temporal lobe cortical thickness and surface area. AB - The volume of parcellated cortical regions is a composite measure related to both thickness and surface area. It is not clear whether volumetric decreases in medial temporal lobe (MTL) cortical regions in aging and Alzheimer's disease (AD) are due to thinning, loss of surface area, or both, nor is it clear whether aging and AD differ in their effects on these properties. Participants included 28 Younger Normals, 47 Older Normals, and 29 patients with mild AD. T1-weighted MRI data were analyzed using a novel semi-automated protocol (presented in a companion article) to delineate the boundaries of entorhinal (ERC), perirhinal (PRC), and posterior parahippocampal (PPHC) cortical regions and calculate their mean thickness, surface area, and volume. Compared to Younger Normals, Older Normals demonstrated moderately reduced ERC and PPHC volumes, which were due primarily to reduced surface area. In contrast, the expected AD-related reduction in ERC volume was produced by a large reduction in thickness with minimal additional effect (beyond that of aging) on surface area. PRC and PPHC also showed large AD-related reductions in thickness. Of all these MTL morphometric measures, ERC and PRC thinning were the best predictors of poorer episodic memory performance in AD. Although the volumes of MTL cortical regions may decrease with both aging and AD, thickness is relatively preserved in normal aging, while even in its mild clinical stage, AD is associated with a large degree of thinning of MTL cortex. These differential morphometric effects of aging and AD may reflect distinct biologic processes and ultimately may provide insights into the anatomic substrates of change in memory-related functions of MTL cortex. PMID- 17869387 TI - Synthesis and structure-activity relationships of N-6 substituted analogues of 9 hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of Wee1 and Chk1 checkpoint kinases. AB - A series of N-6 substituted 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H) diones were prepared from N-substituted (5-methoxyphenyl)ethenylindoles. The target compounds were tested for their ability to inhibit the G2/M cell cycle checkpoint kinases, Wee1 and Chk1. Analogues with neutral or cationic N-6 side chains were potent dual inhibitors. Acidic side chains provided potent (average IC(50) 0.057 microM) and selective (average ratio 223-fold) Wee1 inhibition. Co crystal structures of inhibitors bound to Wee1 show that the pyrrolo[3,4 c]carbazole scaffold binds in the ATP-binding site, with N-6 substituents involved in H-bonding to conserved water molecules. HT-29 cells treated with doxorubicin and then target compounds demonstrate an active Cdc2/cyclin B complex, inhibition of the doxorubicin-induced phosphorylation of tyrosine 15 of Cdc2 and abrogation of the G2 checkpoint. PMID- 17869388 TI - Concomitant administration of Yersinia pestis specific monoclonal antibodies with plague vaccine has a detrimental effect on vaccine mediated immunity. AB - Antibodies can be used to confer rapid immunity against infectious agents for short periods of time. By comparison, vaccine induced immunity is more protective, but takes a relatively long time to develop. Concomitant administration of antibody and vaccine by different routes was evaluated as a means of providing both rapid and long-term protection against plague. BALB/c mice were treated intraperitoneally with monoclonal antibodies, with specificities for Yersinia pestis LcrV and F1 antigens. A cohort of these mice was simultaneously vaccinated with rF1 and rLcrV by the intramuscular route. Antibody co-administration with vaccine reduced the level of vaccine mediated protection afforded against a high level Y. pestis challenge. Conversely, antibody-mediated protection was unaffected by vaccine co-administration and lasted for at least 8 weeks post administration. We also evaluated the effect of administering vaccine intradermally and antibody intratracheally and observed that, irrespective of administration route, concomitant administration of antibody reduced the effectiveness of vaccine mediated immunity. The results of passive transfer experiments supported the thesis that the development of protective antibody responses following vaccination is impaired by the presence of circulating monoclonal antibodies with specificities for important B-cell epitopes in the vaccine. We also noted that intradermal injection of LcrV antigen and cholera toxin adjuvant afforded good levels of protection against systemic and aerosol challenge with Y. pestis: intradermal injection might therefore be considered as a potential minimally invasive method of plague vaccine administration. These data have implications for the design of therapeutic strategies against plague infection. PMID- 17869389 TI - Field effectiveness of vaccination against tick-borne encephalitis. AB - Tick-borne encephalitis (TBE) is a vaccine-preventable disease caused by a flavivirus (TBE virus) that is endemic in many European countries and large parts of Central and Eastern Asia. In Europe, highly purified formalin-inactivated whole virus vaccines are in widespread use, but the vaccination coverage differs significantly between countries with TBE endemicity. Austria presents an exceptional situation because 88% of the total population have a history of TBE vaccination, with 58% being regularly vaccinated within the recommended schedule. In this study, we investigated the field effectiveness of TBE vaccination in Austria for the years 2000-2006 in different age groups on the basis of the documented numbers of hospitalized cases in unvaccinated and vaccinated people and the sizes of these population groups as revealed by representative inquiries. We show that the overall effectiveness in regularly vaccinated persons is about 99% with no statistically significant difference between age groups. It is at least as high after the first two vaccinations, i.e. before the completion of the basic vaccination scheme by a third vaccination, but is significantly lower (about 95%) in those with a record of irregular vaccination. Our data confirm the excellent performance of TBE vaccine under field conditions and provide evidence that, in Austria, about 2800 cases were prevented by vaccination in the years 2000-2006. PMID- 17869390 TI - Distribution and correlation of the natural radionuclides in a coal mine of the West Macedonia Lignite Center (Greece). AB - The distribution and correlation of six natural nuclides in the West Macedonia Lignite Center, Northern Greece were studied. Fifty-five samples of lignite, aged from 1.8 to 5 million years, and corresponding steriles, beds of marls, clays and sands alternating with the lignite, were collected perpendicular to the mine benches and measured spectroscopically. The mean concentrations of (238)U and (226)Ra in lignites were found to be higher than that in steriles since these nuclides are associated with the organic material of lignite, whereas (238)U/(226)Ra equilibrium was not observed in either lignites or steriles. Finally, the ratio (226)Ra/(228)Ra in lignites was approximately double of that in steriles, confirming the affinity of the (238)U series with the coal matrix in contrast to the (232)Th series. No correlation was found between radionuclide concentrations and the depth of the sample, nor with the ash content of lignite. PMID- 17869391 TI - Generic approaches to transfer. AB - A review of methods which have been used to describe and predict transfer of radionuclides in biota was undertaken. The intent was to identify approaches that might prove useful in extending predictive estimates to other organisms and environments. Empirical approaches, such as found in the use of transfer factors, were examined. Kinetic methodologies were also presented. Allometric functions, with their ability to make broad generalizations, were also discussed. Data from several earlier radioecological assessments were tested for their potential utility in developing allometric relationships, with the result implying that such an approach might prove useful. PMID- 17869392 TI - Preliminary evaluation of (135)Cs/(137)Cs as a forensic tool for identifying source of radioactive contamination. AB - Ratios of the fission products (135)Cs and (137)Cs were determined in soil and sediment samples contaminated from three different sources, to assess the use of (135)Cs/(137)Cs as an indicator of source of radioactive contamination. Soil samples from the Chernobyl exclusion zone were found to have to be heavily depleted in (135)Cs ((135)Cs/(137)Cs approximately 0.45), indicative of a high thermal neutron flux at the source. Sludge samples from a nuclear waste treatment pond were found to have a (135)Cs/(137)Cs ratio of approximately 1, whereas sediment collected downstream from a nuclear reactor was highly variable in both (137)Cs activity and (135)Cs/(137)Cs ratio. Comparison of these preliminary results of variability in radiocaesium isotope ratios with reports of Pu isotope ratios suggests (135)Cs/(137)Cs similarly varies with fuel and reactor conditions, and may be used to corroborate other methods of characterizing radioactive contamination. PMID- 17869393 TI - Bachelor of Midwifery students' experiences of achieving competencies: the role of the midwife preceptor. AB - OBJECTIVES: to explore and describe Bachelor of Midwifery students' learning experiences, specifically the role of the midwifery preceptor in learning and development of competency, from the students' perspective. The findings reported are taken from a wider investigation into Bachelor of Midwifery student's achievement of competency. DESIGN: grounded theory methodology using in-depth interviews for data collection. SETTING: school of nursing and midwifery of one university, and associated clinical teaching hospitals in Victoria, Australia. PARTICIPANTS: eight Bachelor of Midwifery students completing their final clinical placement. FINDINGS: data analysis in the broader study identified the categories of: hands-on practice; reflecting on practice; building confidence; gaining knowledge; working with midwives; and constructing a sense of self as a midwife. This paper focuses on one category 'working with midwives', which encompasses the therapeutic, interpersonal and clinical characteristics of the preceptor and their impact on student learning. Generally speaking, students identified midwife preceptors as helpful and unhelpful, and students indicated that they prefer to work with a caring midwife preceptor, who enjoys teaching, answers questions fairly and is philosophically similar. Students also felt that they benefited from opportunities for responsibility for care under supportive supervision, hands-on learning and debriefing. Midwife preceptors described as unhelpful were poor role models, did not allow the space for 'hands-on' practice or 'took over', were generally unsupportive and operated in a hierarchical system within the clinical agencies. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: a positive midwife preceptor-student relationship is an integral part of successful student midwife learning, and preceptors with helpful qualities enhance learning. Hands-on learning was emphasised as the most beneficial learning experience and students sought opportunities to work with midwives who imbued the philosophy they admired rather than becoming desensitised or socialised into a midwifery culture that was at odds with the course's philosophy. These findings are potentially useful to inform midwives and agencies teaching student midwives about preceptor behaviours helpful for student midwife learning. PMID- 17869394 TI - Assessment of biological effects of environmental pollution along the NW Mediterranean Sea using red mullets as sentinel organisms. AB - A biomonitoring program was carried out in spring and autumn in three pollution hot-spots and sensitive areas of the NW Mediterranean Sea using red mullets (Mullus barbatus) as sentinel organisms and a battery of biomarkers together with gonad histology. In fish from anthropogenic impacted areas (Fos-sur-mer, Cortiou, Arenzano, Delta of Ebro) lysosomal membrane destabilization occurred indicating disturbed health. There were no significant differences in metallothionein (MT) levels among stations. Peroxisomal acyl-CoA oxidase (AOX) activity was highest in fish from Cortiou. Both MT levels and AOX activities were significantly correlated with gamete development. Prevalence of melanomacrophage centers were high in Cortiou in all samplings and in Fos-sur-mer in September samplings. In conclusion, the application of a battery of biomarkers in red mullets provided relevant data for the assessment of environmental pollution in the NW Mediterranean Sea but also showed the difficulties of using native fish as sentinels. For future studies caging strategies are recommended. PMID- 17869395 TI - The impact of synthetic pyrethroid and organophosphate sheep dip formulations on microbial activity in soil. AB - Sheep dip formulations containing organophosphates (OPs) or synthetic pyrethroids (SPs) have been widely used in UK, and their spreading onto land has been identified as the most practical disposal method. In this study, the impact of two sheep dip formulations on the microbial activity of a soil was investigated over a 35-d incubation. Microbial utilisation of [1-(14)C] glucose, uptake of (14)C-activity into the microbial biomass and microbial numbers (CFUs g(-1) soil) were investigated. In control soils and soils amended with 0.01% sheep dip, after 7d a larger proportion of added glucose was allocated to microbial biomass rather than respired to CO(2). No clear temporal trends were found in soils amended with 0.1% and 1% sheep dips. Both sheep dip formulations at 0.1% and 1% concentrations resulted in a significant increase in CFUs g(-1) soil and [1-(14)C] glucose mineralisation rates, as well as a decline in microbial uptake of [1-(14)C] glucose, compared to control and 0.01% SP- or OP-amended soils. This study suggests that the growth, activity, physiological status and/or structure of soil microbial community may be affected by sheep dips. PMID- 17869396 TI - Detection of antibodies against therapeutic proteins in the presence of residual therapeutic protein using a solid-phase extraction with acid dissociation (SPEAD) sample treatment prior to ELISA. AB - The evaluation of the potential immunogenicity of therapeutic proteins in nonclinical safety studies has become complicated by the development of biopharmaceuticals that are dosed at high concentrations and/or have long half lives. These products remain in the circulation of the test system for extended periods of time, resulting in samples containing high concentrations of drug that interfere with standard immunogenicity assays. This protocol describes a novel solid-phase extraction with acid dissociation (SPEAD) sample treatment that removes the interfering therapeutic protein "drug" from the sample prior to performance of a direct immunoassay for detection of anti-drug antibodies (ADA). A biotin-avidin capture technique is used to physically separate ADA and ADA:Drug complexes from the drug and the sample matrix. The acid dissociation step removes the ADA from the biotin-avidin complex, and detection is performed by simple direct enzyme-linked immunoassay (ELISA). The SPEAD treatment allows for detection of ADA in an ELISA format and results in a >10-100-fold increase in residual drug tolerance as compared to an immunoassay without the sample treatment. The method can be used for serum samples from all species, but is presented here as an assay for detection of anti-drug antibodies in cynomolgus monkey serum. PMID- 17869397 TI - In vivo protective effect of Porphyra yezoensis polysaccharide against carbon tetrachloride induced hepatotoxicity in mice. AB - To study the protective effect and possible mechanism of Porphyra yezoensis polysaccharide (PYP) in hepatotoxicity mice, acute liver injury was successfully induced by injecting 0.2% carbon tetrachloride (CCl(4)) intraperitoneally. Levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and liver homogenate, content of malondialdehyde (MDA), activities of total superoxide dismutase (T-SOD) in liver were measured by biochemical methods. Liver index was calculated and pathological changes of the liver tissue were observed microscopically. PYP was found to significantly decrease the activities of ALT and AST (P<0.05), to remarkably lower the liver indexes and MDA level in hepatical tissues in mice (P<0.05), and to upregulated the lower T-SOD level in liver homogenate (P<0.01). Furthermore, histologic examination showed that PYP could attenuate and the extent of necrosis, reduce the immigration of inflammatory cells. PYP plays a protective action against hepatotoxicity induced by CCl(4) in mice, and its mechanisms may be related to free radical scavenging, increasing SOD activities and anti-lipid peroxide. PMID- 17869398 TI - Factors affecting Taiwanese women's choice of Cesarean section. AB - The rising rate of cesarean section (CS) is a subject of concern, intensive discussion, and investigation. However, few, if any, systematic studies of this trend have been recorded among the oriental populations. This study examines factors that may contribute to the high incidence of CS in Taiwan, where the rate of CS is among the highest in the world. Multiple logistic regression and stratified analyses were used to determine the association between CS and various factors, including provider and patient parameters. Our study sample of 2,497 cases was drawn from a total of 10,654 in-patient deliveries in Chang Gung Memorial Hospital of Taiwan. A number of factors associated with the use of CS were explored, including maternal age, occupation, education and marital status of the mother, sex and body weight of the infant at birth, parity, insurance status, source of admission, and time of birth. Our study also shows that CS in Taiwan is affected by the folk belief of Pe-Ji, which influences the preference of some patients for delivery at a specific time. Such a preference reflects a unique right of choice by women in Taiwan. PMID- 17869399 TI - Power based association analysis (PBAT) of serotonergic and noradrenergic polymorphisms in bipolar patients with suicidal behaviour. AB - BACKGROUND AND AIMS: Suicidality is a major health concern worldwide particularly in affective disorder patients. Attempted suicide is familial. There is strong neurobiological evidence showing that serotonergic and noradrenergic dysfunction is implicated in suicidal behaviours. We will apply now a new family based association strategy aimed to explain the genetic influence in suicidal behaviour by power based association test statistics (PBAT) in 336 bipolar patients assessed for suicidality within nuclear families. METHODS: By use of conditional power calculations, the approach screens all possible null hypotheses without biasing the nominal significance level, and it identifies the subset of phenotypes that has optimal power when tested for association by either univariate or multivariate family based association test (FBAT). Using this statistical approach (PBAT) we investigated polymorphisms in serotonergic and noradrenergic genes, considering suicidal behaviour severity instead of the dichotomous phenotype (presence of suicide attempt). RESULTS: COMT Val/Met polymorphism was not associated with suicide with high confidence (power=91%). On the other hand, the analysis of the other 12 markers in the adrenergic and serotonergic genes revealed that the TH allele tended towards association with higher severity of suicidal behaviour (p=0.060) but the power obtained was very low. CONCLUSIONS: The marginal finding of association between TH and severe suicidal behaviour are convergent with previous reports. On the other hand, our sample has enough power to exclude the other polymorphisms investigated as major candidate for suicidality in bipolar disorder. PMID- 17869400 TI - Birth months and vulnerability to juvenile delinquency. AB - BACKGROUND: Birth months have been shown to affect susceptibility to schizophrenia and other mental disorders, thus this factor could also affect predisposition to delinquency through biological effects on brain development and personality and/or through relative age effects at school. This study aimed to examine the relationship between birth-season and relative age at school on the risk of delinquency. METHODS: We investigated the ratio of observed and expected births in winter/summer and that in the first/last months of the Japanese school year in 5008 young male Japanese delinquents. RESULTS: No significant difference was found between observed and expected numbers of births in winter/summer or those in the first/last months of the school year. CONCLUSIONS: The present study did not provide evidence for any effect from season of birth or a relative age effect within the school year on the risk of delinquency in Japanese male teenagers. PMID- 17869402 TI - Enamel diffusion modulated by Er:YAG laser (Part 1)--FRAP. AB - Several studies have demonstrated the caries protective effect of lasers by strengthening enamel crystalline structure. However, the effect of laser on enamel diffusion (ED) remains unclear. OBJECTIVES: This study aimed to quantify the laser-induced alteration of diffusion coefficients (DC) in enamel using fluorescence recovery after photobleaching (FRAP). METHODS: Eleven caries-free enamel sections were characterized morphologically using stereomicroscopy, polarized light microscopy and scanning electron microscopy, before and after laser treatment with Er:YAG laser 50 mJ x 5 s x 5 Hz. With 20 microM fluorescein, DCs were measured (n=11) by FRAP coupled with confocal microscopy. RESULTS: The DCs measured were 2.89+/-0.61 x 10(-7)cm(2)/s and 4.076+/-0.73 x 10(-7)cm(2)/s, at the lased and unlased areas, respectively (p=0.001). CONCLUSIONS: This study has confirmed the reduction of ED as a potential mechanism involved in laser induced caries prevention. FRAP was demonstrated to be a promising technique for evaluating diffusion-related phenomenon in enamel. PMID- 17869401 TI - An investigation of the effects of methylmercury in rats fed different dietary fats and proteins: testicular steroidogenic enzymes and serum testosterone levels. AB - Methylmercury (MeHg) is a testicular toxicant causing reduced steroidogenic enzyme activity, reduced serum testosterone (T) and abnormal spermatogenesis in mammals and fowl. It is also known that certain diets can alter androgen metabolism in rats. Previously we have shown that diets used in the current study impact circulating androgen levels and testicular steroidogenic enzyme activities in Sprague Dawley rats in the absence of MeHg. In the present study, we have investigated the impact of imposing an environmental contaminant (MeHg) commonly found in marine mammals and fish onto the rats' dietary intake of different proteins and lipids in order to determine if the different diets could modify MeHg toxicity in rats. Therefore, we examined the effects of MeHg on testicular steroidogenic enzymes and serum testosterone in rats fed diets containing either different protein sources (casein, fishmeal, whey) or different lipid sources (soybean oil, docosahexaenoic acid (DHA), seal oil, fish oil, lard). Male rats 42 45 days of age (18 per group) were assigned to different experimental diets for 28 days after which 6 rats in each group were gavaged daily with 0, 1 or 3 mg/kg body weight (BW)/day MeHg chloride in 5 mM Na(2)CO(3) solution for 14 days while being maintained on their diets. On the 43rd day of dosing, rats were sacrificed and blood plasma and testes frozen (-80 degrees C) until analysis. Microsomal steroidogenic enzyme activities (3beta-HSD, 17-OHase, C-17, 20-lyase, 17beta-HSD) were measured radiometrically. Serum testosterone was determined using ELISA kits. Testis weights were not affected by MeHg. MeHg at 3 mg/kg BW/day caused a reduction (>50%) in the activity of C-17, 20-lyase in all three protein diets and similar reductions in 17-OHase activity were seen in the casein and whey protein fed rats. At 3 mg/kg BW/day, MeHg reduced 17-OHase activity in the DHA diet but had no effect on 3beta-HSD activity and no inhibitory effects on 17beta-HSD activity. MeHg (3 mg/kg BW/day) caused significant reductions in serum T in the whey, soybean oil and fish oil groups. Interestingly, fishmeal protein but not fish oil offered some protection with respect to maintaining steroidogenic enzyme activities and serum T levels in rats dosed with MeHg. In conclusion, these studies show that different lipid diets can alter the toxic effects of MeHg on male rat steroidogenesis in terms of serum testosterone and steroidogenic enzyme activities. PMID- 17869403 TI - The effect of 24h non-stop hydrogen peroxide concentration on bovine enamel and dentine mineral content and microhardness. AB - OBJECTIVES: Tooth bleaching agents may adversely affect tooth structure. The aim of this study was to investigate the effect of hydrogen peroxide concentration on mineral loss and microhardness of bovine teeth. METHODS: Twenty-six freshly extracted intact bovine incisor teeth were stored in distilled water. Five teeth were sectioned and four samples (2 mm x 2 mm x 1.5 mm) each of enamel and dentine were obtained from each tooth. The samples of enamel and dentine were divided into four groups and immersed in either 0%, 3%, 10% or 30% (w/v) hydrogen peroxide solutions for 24h at 37 degrees C. Samples from the solutions were taken for ion release analysis using inductively coupled plasma mass spectrometry. The remaining 21 teeth were mounted in epoxy resin and the upper surface of the specimens were ground and polished to expose the enamel and dentine for microhardness measurements. These specimens were randomly divided into three equal groups and Vickers microhardness values were recorded on the enamel and dentine surfaces of each group before and after bleaching. RESULTS: The differences in ion release concentration after treatment with 0% (control) and each of 3%, 10% and 30% hydrogen peroxide (w/v) were statistically significant (p<0.025). The release of calcium and phosphorous ions increased with increasing hydrogen peroxide concentrations. A significant reduction (p<0.05) in Vickers microhardness values for enamel was recorded after bleaching. CONCLUSIONS: Ion release from both enamel and dentine increased with increasing hydrogen peroxide concentration. Microhardness of enamel decreased significantly with bleaching. PMID- 17869404 TI - Enamel diffusion modulated by Er:YAG laser (Part 2). Organic matrix. AB - Organic matrix (OM) has been hypothesized as a key player in the laser-induced retardation of enamel diffusion (LRED). OBJECTIVES: Therefore, this study was aimed to quantify the contribution of OM in LRED. METHODS: Four groups of enamel sections (n=10) were assigned to 'normal', 'laser treated', 'OM extracted' and 'laser+OM extraction' groups for measurement of diffusion coefficient (DC) using fluorescence recovery after photobleaching (FRAP) and fluorophores transport study (FTS). Er:YAG laser treatment and OM extraction were performed on respective groups. Sections were characterized with stereomicroscopy and polarized light microscopy. Treatment effects were statistically assessed with a factorial ANOVA. RESULTS: DC measured by FRAP and FTS coupled with confocal microscopy revealed the significant effect of OM (p=0.001) and laser treatment (p<0.01). After OM extraction, the laser effect on diffusion decreased about 34 75%, confirming the significant role of OM in LRED. CONCLUSION: Both FRAP and FTS may be promising tools to quantify enamel DC. PMID- 17869405 TI - Breast metastasis in a pregnant woman with alveolar rhabdomyosarcoma of the upper extremity. PMID- 17869406 TI - Doppler indices in the umbilical arteries: influence of vessel curvature induced by bladder filling. AB - Doppler indices are widely used to assess normal versus pathologic haemodynamics. In obstetrics, the assessment of abnormal values in some critical compartments, such as the umbilical arteries (UA), may be crucial in the clinical management of growth-restricted foetuses. It was recently proposed that the UA should be sampled in their perivesical portion (PVC), i.e., where they surround the foetal urinary bladder. However, measurements at this site could be biased by the degree of curvature of the vessel due to bladder filling. We investigated this possibility in vivo and in vitro, i.e., measurements on rubber tubes at different radii of curvature R(c). There was significant dependence of the Doppler indices A/B and PI on the vessel curvature and insonation angle; in fact, we recorded errors of about 25% when R(c) was 10 times larger than the radius of the vessel and about 100% when R(c) was five times larger than the radius of the vessel. Therefore, measurements of the UA at the PVC site should only be performed when the foetal bladder is empty. PMID- 17869407 TI - Editorial comment on: holmium laser enucleation of the prostate versus open prostatectomy for prostates greater than 100 grams: 5-year follow-up results of a randomised clinical trial. PMID- 17869408 TI - Editorial comment on: holmium laser enucleation of the prostate versus open prostatectomy for prostates greater than 100 grams: 5-year follow-up results of a randomised clinical trial. PMID- 17869409 TI - Holmium laser enucleation of the prostate versus open prostatectomy for prostates greater than 100 grams: 5-year follow-up results of a randomised clinical trial. AB - OBJECTIVES: To report 5-year follow-up results of a randomised clinical trial comparing holmium laser enucleation of the prostate (HoLEP) with open prostatectomy (OP). METHODS: One hundred twenty patients with prostates greater than 100g in weight according to transrectal ultrasound were randomised to either the HoLEP or the OP group (ie, 60 patients to each group). Preoperative and postoperative assessments included American Urological Association Symptom Score (AUA-SS), maximum urinary flow rates (Qmax), and postvoid residual urine (PVRU) volumes. Measurements were performed at 1, 3, 6, 12, 18, 24, 36, 48, and 60 mo. Postoperative outcome data were compared. All complications were recorded. RESULTS: Five years postoperatively, a total of 46 patients (38.3%) were lost to follow-up or had to be excluded from the study. All the remaining 74 patients (42 HoLEP vs. 32 OP patients, p=0.11) had undergone the 5-yr follow-up assessments. Mean AUA-SS was 3.0 in both groups (p=0.98), mean Qmax was 24.4 ml/s in both groups (p=0.97) and PVRU volume was 11 ml in the HoLEP and 5 ml in the OP group (p=0.25). Late complications consisted of urethral strictures and bladder-neck contractures; reoperation rates were 5% in the HoLEP and 6.7% in the OP group (p=1.0). No patient developed benign prostatic hyperplasia recurrence. CONCLUSIONS: Five years after the operation, the improvements in micturition obtained with HoLEP and OP were equally good, and reoperation rates similarly low. HoLEP seems to be a true endourological alternative to OP. PMID- 17869410 TI - Steroid effects on intracellular degradation of insulin and crinophagy in isolated pancreatic islets. AB - Under physiological conditions substantial amounts of hormone may be degraded within endocrine cells by a crinophagic process comprising fusions of secretory granules with lysosomes. Glucocorticoids may stabilise and progesterone destabilise lysosomal membranes. The effects of corticosterone and progesterone on intracellular degradation of insulin and crinophagy were determined in pancreatic beta-cells, and possible pathways mediating these effects were evaluated. Pancreatic islets were isolated from mice, intracellular degradation of insulin was measured by a pulse-chase method, and crinophagy was studied by electron microscopy. The islets were exposed to 3.3, 5.5 or 28 mM glucose with or without corticosterone, progesterone or the receptor ligands A-224817.0 and WAY 161358. Mifepristone was used to block steroid receptors and indomethacin to inhibit prostaglandin synthesis. Corticosterone caused a concentration-dependent decrease of insulin degradation at the lower glucose concentrations. Progesterone effected a concentration-dependent stimulation of insulin degradation. These results were paralleled with changes of the crinophagic activity in the beta cells. Corticosterone decreased and progesterone increased islet production of prostaglandin E(2). Mifepristone abolished the steroid actions on insulin degradation and prostaglandin production. The effects of corticosterone were mimicked by the selective glucocorticoid receptor modulator A-224817.0, but in contrast to progesterone, the selective progesterone receptor agonist WAY-161358 had no effect on insulin degradation or prostaglandin production. Inhibition of cyclooxygenase blocked insulin degradation. The findings indicate that both corticosterone and progesterone could affect intracellular insulin degradation and crinophagy solely via the glucocorticoid receptor, and that prostaglandins may have a regulatory role in intracellular turnover of secretory material in pancreatic islet beta-cells. PMID- 17869411 TI - Inhibitory effects of nitric oxide on invasion of human cancer cells. AB - Hypoxia increased the ability of two human cancer cell lines, PC-3M and T24, to invade through Matrigel, while sodium nitroprusside (SNP), a nitric oxide (NO) donor, strongly inhibited this invasion, along with down-regulating HIF-1alpha. SNP also inhibited the function of mitochondria in PC-3M cells, and mitochondrion specific inhibitors reduced the invasion of these cells. Furthermore, knocking down either Rieske iron-sulfur protein (Fe-S) of mitochondrial complex III or HIF 1beta in these cells decreased their invasive potential. Our findings suggest that NO inhibits invasion of cancer cells via both inhibition of HIF-1, and impairment of mitochondria. PMID- 17869412 TI - Wild-type class I beta-tubulin sensitizes Taxol-resistant breast adenocarcinoma cells harboring a beta-tubulin mutation. AB - A Taxol-resistant cell line, K20T, which does not express P-glycoprotein, was selected with Taxol from human MDA-MB-231 breast adenocarcinoma cells and maintained in the presence of 20nM Taxol. K20T cells were approximately 18-fold resistant to Taxol, displayed cross-resistance to Taxotere and the epothilones, but little cross-resistance to discodermolide. Sequence analysis of the class I beta-tubulin indicated that it harbored an A593G mutation resulting in a change from glutamate to glycine at amino acid 198, which is near the intradimer interface within the alpha/beta-tubulin heterodimer. An HA-tagged wild-type class I beta-tubulin expression vector was transfected into the K20T cells. Immunofluorescence studies demonstrated that this exogenous tubulin was incorporated into cellular microtubules and Western blot analysis indicated that the K20T transfectants predominantly expressed the exogenous wild-type class I beta-tubulin. The transfected cells were only approximately 5-fold resistant to Taxol. Our results, plus the knowledge that Glu198 is the target for other anti tubulin agents, suggest that glutamate198 in beta-tubulin is a critical determinant for microtubule stability and Taxol resistance. PMID- 17869413 TI - Preparation of sludge-based activated carbon and its application in dye wastewater treatment. AB - A novel activation process was adopted to produce highly porous activated carbon from cyclic activated sludge in secondary precipitator in municipal wastewater treatment plant for dye removal from colored wastewater. The physical properties of activated carbon produced with the activation of 3M KOH solution in the atmosphere of steam were investigated. Adsorption removal of a dye, Acid Brilliant Scarlet GR, from aqueous solution onto the sludge-based activated carbon was studied under varying conditions of adsorption time, initial concentration, carbon dosage and pH. Adsorption equilibrium was obtained in 15 min for the dye initial concentration of 300 mg/L. Initial pH of solution had an insignificant impact on the dye removal. Results indicated that 99.7% coloration and 99.6% total organic carbon (TOC) were removed after 15 min adsorption in the synthetic solution of Acid Brilliant Scarlet GR with initial concentration of 300 mg/L of the dye and 20 g/L activated carbon. The Langmuir and Freundlich equilibrium isotherm models fitted the adsorption data well with R(2)=0.996 and 0.912, respectively. Accordingly, it is concluded that the procedure of developing activated carbon used in this study could be effective and practical for utilizing in dye wastewater treatment. PMID- 17869414 TI - Utilization of steel slag for Portland cement clinker production. AB - The aim of the present research work is to investigate the possibility of adding steel slag, a by-product of the conversion of iron to steel process, in the raw meal for the production of Portland cement clinker. Two samples of raw meals were prepared, one with ordinary raw materials, as a reference sample ((PC)(Ref)), and another with 10.5% steel slag ((PC)(S/S)). Both raw meals were sintered at 1450 degrees C. The results of chemical and mineralogical analyses as well as the microscopic examination showed that the use of the steel slag did not affect the mineralogical characteristics of the so produced Portland cement clinker. Furthermore, both clinkers were tested by determining the grindability, setting times, compressive strengths and soundness. The hydration products were examined by XRD analysis at 2, 7, 28 and 90 days. The results of the physico-mechanical tests showed that the addition of the steel slag did not negatively affect the quality of the produced cement. PMID- 17869415 TI - An assessment of the role of intracellular reductive capacity in the biological clearance of triarylmethane dyes. AB - The second-order rate constants (at pH 7, 25 degrees C) for the reduction of three cationic triarylmethane dyes [pararosaniline (PR+), malachite green (MG+), methyl green (MeG+)] by NADH were 1.4 x 10(-2) to 6.7 x 10(-2)mM(-1)min(-1). Based on these values the intracellular nonenzymatic reduction of TAM+ to TAM-H by endogenous NADH was estimated to proceed with an average half-life of 30 min. Rapid and significant adduct formation was observed with the thiol, 3 mercaptopropionic acid (MPA), suggesting that the primary intracellular form of the dyes must be a thiol adduct and that the conversion to adduct form takes place within ms-s. These time frames, when compared to the min-h time frame for microbial clearance of triarylmethanes from culture media, suggest that transport must be the rate-limiting step in non-adsorptive (chemical) clearance of the dyes and that the presence of enzymes to complement the nonenzymatic reductive and adduct-forming activities cited serves a kinetically limited purpose. It appears that a superior catalytic scavenger will be one with a superior transport capacity. PMID- 17869416 TI - Removal of colour and COD from wastewater containing acid blue 22 by electrochemical oxidation. AB - Electrochemical oxidation of synthetic wastewater containing acid blue 22 on a boron-doped diamond electrode (BDD) was studied, using cyclic voltammetry and bulk electrolysis. The influence of current density, dye concentration, flow rate, and temperature was investigated, in order to find the best conditions for COD and colour removal. It was found that, during oxidation, a polymeric film, causing BDD deactivation, was formed in the potential region of water stability, and that it was removed by anodic polarisation at high potentials in the region of O(2) evolution. Bulk electrolysis results showed that the electrochemical process was suitable for completely removing COD and effectively decolourising wastewaters, due to the production of hydroxyl radicals on the diamond surface. In particular, under optimal experimental conditions of flow rates (i.e. 300 dm(3) h(-1)) and current density (i.e. 20 mA cm(-2)), 97% of COD was removed in 12h electrolysis, with 70 kWh m(-3) energy consumption. PMID- 17869417 TI - Anaerobic biodegradation of fluoranthene under methanogenic conditions in presence of surface-active compounds. AB - Bacillus cereus isolated from municipal wastewater treatment plant was used as a model strain to assess the efficiency of two anionic surfactants, a chemical surfactant and a biosurfactant during fluoranthene biodegradation under anaerobic methanogenic conditions. The surfactants selected for the study were linear alkyl benzene sulphonates (LAS) and rhamnolipid-biosurfactant complex from Pseudomonas sp. PS-17. Biodegradation of fluoranthene was monitored by GC/MS for a period up to 12th day. No change in the fluoranthene concentration was registered after 7th day. The presence of LAS enhanced the cell growth as well as the fluoranthene biodegradation. The rhamnolipid-biosurfactant at both used concentrations inhibited the cell growth and had no effect on the biodegradation rate. It was shown that LAS did not affect the microbial cell permeability and its positive effect on fluoranthene biodegradation was most likely as a result of the increased fluoranthene solubility. The results indicate that LAS can be considered as a promising agent for facilitation of the process of anaerobic polycyclic aromatic hydrocarbons (PAH) biodegradation under methanogenic conditions. PMID- 17869418 TI - Photodegradation of an azo dye using immobilized nanoparticles of TiO2 supported by natural porous mineral. AB - Natural mordenite, replacing the synthetic zeolites, has been employed as the support of TiO2, and its photocatalytic activity has been examined in methyl orange (MO) aqueous under UV light. AFM, TEM, XRD, FTIR and fluorescence spectra have been used to reveal the loading effects of TiO2 on mordenite. The results show that the photocatalytic degradation (PCD) reaction rates are sharply increased by natural zeolite supports. Since mordenite is photo-inert, the PCD enhancement is mostly caused by the bonding effects of Ti-O-Si and Ti-O-Al. Moreover, another two distinct natural zeolites have been employed as the supports of TiO2, in order to check the universality of PCD-enhancement effect of natural zeolites on TiO2. And the factors of PCD reaction on TiO2-zeolite, such as pH and catalyst dose, have been investigated. PMID- 17869419 TI - Growth responses of three ornamental plants to Cd and Cd-Pb stress and their metal accumulation characteristics. AB - Up to now, there was no document on ornamental plants that had been applied to phytoremediation, which can remedy contaminated environment and beautify it at the same time. Thus, the growth responses and possible phytoremediation ability of three ornamental plants selected from the previous preliminary experiments were further examined under single Cd or combined Cd-Pb stress. The results showed that these tested plants had higher tolerance to Cd and Pb contamination and could effectively accumulate the metals, especially for Calendula officinalis and Althaea rosea. For C. officinalis, it grew normally in soils containing 100 mg kg(-1) Cd without suffering phytotoxicity, and the Cd concentration in the roots was up to 1084 mg kg(-1) while the Cd concentration in the shoots was 284 mg kg(-1). For A. rosea, the Cd accumulation in the shoots was higher than that in the roots when the Cd concentration in soils was <100 mg kg(-1), and reached 100 mg kg(-1) as the criteria of a Cd hyperaccumulator when the Cd concentration in soils was 100 mg kg(-1). Their accumulation and tolerance to Cd and Pb were further demonstrated through the hydroponic-culture method. And A. rosea had a great potential as a possible Cd hyperaccumulator under favorable or induced conditions. Furthermore, the interactive effects of Cd and Pb in the three ornamentals were complicated, not only additive, antagonistic or synergistic, but also related to many factors including concentration combinations of heavy metals, plant species and various parts of plants. Thus, it can be forecasted that this work will provide a new way for phytoremediation of contaminated soils. PMID- 17869420 TI - Inhibiting dopamine reuptake blocks the induction of long-term potentiation and depression in the lateral entorhinal cortex of awake rats. AB - Synaptic plasticity in olfactory inputs to the lateral entorhinal cortex may result in lasting changes in the processing of olfactory stimuli. Changes in dopaminergic tone can have strong effects on basal evoked synaptic responses in the superficial layers of the entorhinal cortex, and the current study investigated whether dopamine may modulate the induction of long-term potentiation (LTP) and depression (LTD) in piriform cortex inputs to layer II of the lateral entorhinal cortex in awake rats. Groups of animals were pretreated with either saline or the selective dopamine reuptake inhibitor GBR12909 prior to low or high frequency stimulation to induce LTD or LTP. In saline-treated groups, synaptic responses were potentiated to 122.4+/-6.4% of baseline levels following LTP induction, and were reduced to 84.5+/-4.9% following induction of LTD. Changes in synaptic responses were maintained for up to 60min and returned to baseline levels within 24h. In contrast, induction of both LTP and LTD was blocked in rats pretreated with GBR12909. Dopaminergic suppression of synaptic plasticity in the entorhinal cortex may serve to restrain activity-dependent plasticity during reward-relevant behavioral states or during processing of novel stimuli. PMID- 17869421 TI - Nerve resection and re-location may relieve causalgia: a case report. AB - This article reports the relief of severe causalgia of the right infra-orbital nerve by nerve section and re-location in a 14-year-old boy who had worsening neuropathic pain (NP) and was housebound and refractory to all analgesics for 14 months. His infra-orbital nerve was sectioned and re-located into his buccal fat pad. Severe steady burning, electric shock-like pain and allodynia disappeared and he was able to return to school and an increasingly normal life at one year post-operatively and is pain-free at 3 years and 6 months of follow-up. With NP further deafferentation can cause a worsening of the pain or anaesthesia dolorosa. In this instance there was dramatic and then sequential, gradual and complete resolution of all components of this particular form of NP. Therefore, in selected patients with causalgia this nerve re-location technique may help in symptom resolution and improve quality of life. PMID- 17869422 TI - Chronic pain, impaired glucose tolerance and diabetes: a community-based study. AB - The aim of this study was to analyse how plasma glucose level and diabetes mellitus (DM) are associated with chronic pain in the adult population. A structured interview and health examination study with 480 participants aged 30 65 years was carried out in Lapinlahti municipality in Eastern Finland. Chronic pain (duration of at least 3 months) was graded according to frequency: being present less often than daily, or every day or continuously (daily chronic pain, DCP). Elevated plasma glucose was defined as a plasma glucose level 6.1 mmol/l. DM diagnosis was based on self-reported diagnoses, reimbursed medication or a health examination with laboratory tests. Glucose regulation status was defined according to fasting plasma glucose level and a two-hour glucose tolerance test. Of the total sample, 90 subjects (19%) had a plasma glucose level > or = 6.1 mmol/l and 55 subjects (11%) had diabetes. The prevalence of daily chronic pain was 21% (N = 101) in all the subjects. In the subjects with a normal plasma glucose level, the prevalence was 18%, while in those with an elevated plasma glucose level it was 38%. The corresponding percentages for non-diabetics and diabetics were 19% and 42%. In the multinomial multivariate logistic regression analysis, glucose level or diabetes was associated with DCP. The odds for DCP in the subjects with an elevated plasma glucose level was 2.37 (95% CI, 1.26-4.49), and in those with DM it was 2.53 (95% CI, 1.12-5.72). Elevated plasma glucose level and DM are associated with DCP in adults. PMID- 17869423 TI - Exposure to movement in chronic back pain: evidence of successful generalization across a reaching task. AB - According to the fear-avoidance model, kinesiophobia (pain-related fear) is an important factor in the development of chronic pain and disability through the maintenance of maladaptive avoidance behaviors. Using a paradigm that required repeated exposure to a reaching task, the current study investigated generalization of pain and harm expectancy corrections (i.e., the tendency to bring expectations in line with experience) in chronic low back pain sufferers with high versus low levels of kinesiophobia. Sixty participants were asked to consecutively perform four adaptations of a reaching task, each introducing an element of increased intensity. Expected and experienced pain and harm ratings were collected during the two trials comprising each movement. Individuals with high levels of kinesiophobia reported greater pain and harm ratings during the movements. Further, highly kinesiophobic female, but not male, participants demonstrated greater overprediction of harm relative to low kinesiophobic counterparts during the first reaching trial. Finally, in contrast to previous investigations, highly kinesiophobic participants showed successful generalization of pain expectancy corrections across movement tasks. Possible clinical implications of the findings are noted. PMID- 17869424 TI - Validation of the S-LANSS in the community setting. AB - The Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs (S LANSS), an assessment tool to determine if pain is predominantly neuropathic, has not been validated in a community setting. Previously identified residents of Olmsted County, Minnesota, with chronic pain were recruited using a stratified randomization process to increase the frequency of neuropathic pain in the study sample. Subjects completed the S-LANSS in mailed and telephone formats, and underwent clinical assessment to determine if a component of their pain was neuropathic. Sensitivity and specificity of the S-LANSS as compared to the clinical assessment were determined. Two hundred and five subjects participated in the study. Eighty-three subjects (40%) had a positive S-LANSS score in the mailed, as did 59 of 173 (34%) in the telephone format, with little inter-subject difference in scores (p=0.57). Clinical assessment identified a component of neuropathic pain in 37% of the sample (75/205). Compared to clinical assessment, sensitivity and specificity in the mailed S-LANSS were 57% (95% CI, 46-69%) and 69% (95% CI, 61-77%), respectively, and in the telephone S-LANSS were 52% (95% CI, 39-64%) and 78% (95% CI, 68-85%), respectively. The sensitivity and specificity of the S-LANSS in both formats were lower than the initial S-LANSS validation study. Differences in survey format and subject population could account for these differences, suggesting that the S-LANSS is best suited as a screening tool and its use to determine the prevalence of neuropathic pain in population studies should be viewed cautiously. PMID- 17869425 TI - Cardiovascular distribution of the calcium sensing receptor before and after burns. AB - Due to up-regulation of the parathyroid gland calcium-sensing receptor (CaR), burned children have hypocalcemic hypoparathyroidism, and decreased myocardial contractility. Our aim was to localize the CaR in the heart and measure receptor density changes due to burns. Heart and aorta samples from sheep subjected to 40% burn or sham conditions were probed for CaR via fluorescence microscopy. CaR was localized to endocardial endothelium, myocardial microvasculature, and fibroblasts and vessels of the aortic adventitia. CaR was not found in cardiomyocytes or smooth muscle cells. No differences in density of CaR or beta adrenergic receptors were noted. No differences in CaR distribution were seen in the myocardium or aorta, in contrast to the parathyroid where burn injury up regulates CaR. We suggest that CaR has a local, tissue-specific role, and functions in vascular calcium sensing for intravascular calcium deposition or regulation of other calcium channels after trauma or burn. PMID- 17869426 TI - Classification of skin substitutes. PMID- 17869427 TI - Improving the ability to predict mortality among burn patients. AB - BACKGROUND: Early efforts to predict death following severe burns focused on age and burn size; more recent work incorporated inhalation injury and pneumonia. Gender, co-morbid illness, and co-existent trauma have been implicated in burn mortality but have rarely been incorporated into predictive models. METHODS: The National Burn Repository (NBR) and the National Trauma Data Bank (NTDB) provided data on 68,661 (54,219 and 14,442, respectively) burn patients that was used to develop and validate, respectively, a predictive model of burn mortality. Logistic regression was used to model the odds of mortality with respect to age, gender, % body surface area burned (BSAB), co-existent trauma, inhalation injury, pneumonia, and co-morbid illness. Performance of the predictive model was assessed using a deviance statistic, receiver operating characteristic (ROC) curves, and the Hosmer-Lemeshow (HL) statistic. RESULTS: The predictive model that demonstrated optimal performance included the variables age, percent total BSAB, inhalation injury, co-existent trauma, and pneumonia. The area under the ROC curve for this model was 0.94 and the HL statistic was 16.0. The inclusion of additional variables, i.e., gender, co-morbid illness, did not improve the performance of the model despite reduction in the model deviance. When the predictive model was applied to the validation data source, the area under the ROC curve was 0.87 and the HL statistic was 10.0, indicating good discrimination and calibration. CONCLUSION: The results of this study suggest that a comprehensive predictive model of burn mortality incorporating certain variables not previously considered in other models provides superior predictive ability. PMID- 17869428 TI - Iatrogenic second-degree burn caused by a catheter encased tubular braid of stainless steel during MRI. PMID- 17869429 TI - Analysis of hydrofluoric acid penetration and decontamination of the eye by means of time-resolved optical coherence tomography. AB - So far the study of chemical burns has lacked techniques to define penetration kinetics and the effects of decontamination within biological structures. In this study, we aim to demonstrate that high-resolution optical coherence tomography (HR-OCT) can close this gap. Rabbit corneas were exposed ex vivo to 2.5% hydrofluoric acid (HF) solution, and microstructural changes were monitored in the time domain by OCT imaging. HF application and penetration resulted in shrinkage of the corneal thickness, interpreted as a result of osmolar changes and of loss of water-binding capacity, and a substantial increase in OCT signal amplitudes. The effectiveness of different rinsing solutions on the chemical burn was also evaluated. With tap water and with 1% calcium gluconate, the deep corneal stroma remained clear until the end of the rinsing period but became opaque afterwards. With Hexafluorine, the cornea remained clear for 60 min after rinsing ceased. We conclude that HR-OCT can assist in the clinical evaluation of an ex vivo eye irritation test, and that decontamination of an HF burn using Hexafluorine is efficient. PMID- 17869430 TI - Squamous cell carcinoma arising in a split-thickness skin graft donor site. PMID- 17869431 TI - GLAST1b, the exon-9 skipping form of the glutamate-aspartate transporter EAAT1 is a sensitive marker of neuronal dysfunction in the hypoxic brain. AB - In normal brain, we previously demonstrated that the exon-9 skipping form of glutamate-aspartate transporter (GLAST; which we refer to as GLAST1b) is expressed by small populations of neurons that appear to be sick or dying and suggested that these cells were subject to inappropriate local glutamate-mediated excitation. To test this hypothesis we examined the expression of GLAST1b in the hypoxic pig brain. In this model glial glutamate transporters such as GLAST and glutamate transporter 1 (GLT-1) are down-regulated in susceptible regions, leading to regional loss of glutamate homeostasis and thus to brain damage. We demonstrate by immunohistochemistry that in those brain regions where astroglial glutamate transporters are lost, GLAST1b expression is induced in populations of neurons and to a lesser extent in some astrocytes. These neurons were also immunolabeled by antibodies against the carboxyl-terminal region of GLAST but did not label with antibodies directed against the amino-terminal region. Our Western blotting data indicate that GLAST1b expressed by neurons lacks the normal GLAST amino-terminal region and may be further cleaved to a smaller approximately 30 kDa fragment. We propose that GLAST1b represents a novel and sensitive marker for the detection of neurons at risk of dying in response to hypoxic and other excitotoxic insults and may have wider applicability in experimental and clinical contexts. PMID- 17869432 TI - Endurance exercise promotes cardiorespiratory rehabilitation without neurorestoration in the chronic mouse model of parkinsonism with severe neurodegeneration. AB - Physical rehabilitation with endurance exercise for patients with Parkinson's disease has not been well established, although some clinical and laboratory reports suggest that exercise may produce a neuroprotective effect and restore dopaminergic and motor functions. In this study, we used a chronic mouse model of Parkinsonism, which was induced by injecting male C57BL/6 mice with 10 doses of 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks. This chronic parkinsonian model displays a severe and persistent loss of nigrostriatal neurons, resulting in robust dopamine depletion and locomotor impairment in mice. Following the induction of Parkinsonism, these mice were able to sustain an exercise training program on a motorized rodent treadmill at a speed of 18 m/min, 0 degrees of inclination, 40 min/day, 5 days/week for 4 weeks. At the end of exercise training, we examined and compared their cardiorespiratory capacity, behavior, and neurochemical changes with that of the probenecid-treated control and sedentary parkinsonian mice. The resting heart rate after 4 weeks of exercise in the chronic parkinsonian mice was significantly lower than the rate before exercise, whereas the resting heart rate at the beginning and 4 weeks afterward in the control or sedentary parkinsonian mice was unchanged. Exercised parkinsonian mice also recovered from elevated electrocardiogram R-wave amplitude that was detected in the parkinsonian mice without exercise for 4 weeks. The values of oxygen consumption, carbon dioxide production, and body heat generation in the exercised parkinsonian mice before and during the Bruce maximal exercise challenge test were all significantly lower than that of their sedentary counterparts. Furthermore, the exercised parkinsonian mice demonstrated a greater mass in the left ventricle of the heart and an increased level of citrate synthase activity in the skeletal muscles. The amphetamine-induced, dopamine release-dependent locomotor activity was markedly inhibited in the sedentary parkinsonian mice and was also inhibited in the exercised parkinsonian mice. Finally, neuronal recovery from the loss of nigrostriatal tyrosine hydroxylase expression and dopamine levels in the severe parkinsonian mice after exercise was not evident. Taken all together, these data suggest that 4 weeks of treadmill exercise promoted physical endurance, resulting in cardiorespiratory and metabolic adaptations in the chronic parkinsonian mice with severe neurodegeneration without demonstrating a restorative potential for the nigrostriatal dopaminergic function. PMID- 17869433 TI - Lack of exercise, via hindlimb suspension, impedes endogenous neurogenesis. AB - Bedridden patients who receive good physical rehabilitation are able to exhibit clinical improvement. Accumulating evidence demonstrates that exercise increases endogenous neurogenesis and may even protect against central nervous system (CNS) disorders. Here, we explored the effects of lack of exercise on neurogenesis in rats by employing a routine hindlimb suspension (HS) model over a 2-week period, which consists of elevating their tails, thereby raising their hindlimbs above the ground and unloading the weights in these extremities. In addition, the effects of exercise and recovery time with normal caging after HS were also explored. BrdU (50 mg/kg, i.p.) was injected every 8 h over the last 4 days of each paradigm to label proliferative cells. Immunohistochemical results revealed that HS significantly reduced the number of BrdU/Doublecortin double-positive cells in the subventricular zone and dentate gyrus. Exercise and recovery time significantly improved atrophy of the soleus muscle, but did not attenuate the HS induced decrement in BrdU/Dcx-positive cells. A separate cohort of animals was exposed to the same HS paradigm and enzyme-linked immunosorbent assay (ELISA) of neurotrophic factors was performed on brain tissue samples harvested at the end of the HS period, as well as plasma samples from all animals. ELISA results revealed that HS reduced the levels of brain-derived neurotrophic factor in the hippocampus and vascular endothelial growth factor plasma levels. This study revealed that lack of exercise reduced neurogenesis with downregulation of neurotrophic factors. The use of the HS model in conjunction with CNS disease models should further elucidate the role of exercise in neurogenesis and neurotrophic factors in neurologic disorders. PMID- 17869434 TI - An intact dopaminergic system is required for context-conditioned release of 5-HT in the nucleus accumbens of postweaning isolation-reared rats. AB - We investigated the effect of the tyrosine hydroxylase inhibitor, alpha-methyl para-tyrosine (AMPT) on extracellular dopamine and 5-HT levels in the nucleus accumbens of group- and isolation-reared rats. Microdialysis with high performance liquid chromatography-electrochemical detection was used to quantify dopamine and 5-HT efflux in the nucleus accumbens following foot shock and in association with a conditioned emotional response (CER). Isolation- and group reared rats received i.p. injections of either saline (0.9%) or AMPT (200 mg/kg) 15 h and 2 h prior to sampling. There was no significant difference between saline-treated isolation- or group-reared rats for basal efflux of dopamine or 5 HT, however as expected, AMPT-treatment significantly reduced dopamine efflux in both groups to an equivalent level (50-55% saline-treated controls). Exposure to mild foot shock stimulated basal dopamine efflux in saline-treated groups only, although the effect was significantly greater in isolation-reared rats. In AMPT treated rats, foot shock did not affect basal dopamine efflux in either rearing group. Foot shock evoked a prolonged increase in 5-HT efflux in both isolation- and group-reared saline-treated rats but had no effect on 5-HT efflux in AMPT treated rats. In response to CER, isolation-rearing was associated with significantly greater efflux of both dopamine and 5-HT in saline-treated rats, compared to saline-treated, group-reared controls. However in AMPT-treated rats, efflux of dopamine or 5-HT did not change in response to CER. These data suggest that unconditioned or conditioned stress-induced changes in 5-HT release of the nucleus accumbens are dependent upon intact catecholaminergic neurotransmission. Furthermore, as the contribution of noradrenaline to catecholamine efflux in the nucleus accumbens is relatively minor compared to dopamine, our findings suggest that dopamine efflux in the nucleus accumbens is important for the local regulation of 5-HT release in this region. Finally, these findings implicate the isolation-enhanced presynaptic dopamine function in the accumbens with the augmented ventral striatal 5-HT neurotransmission characterized by isolation reared rats. PMID- 17869435 TI - Modification of purinergic signaling in the hippocampus of streptozotocin-induced diabetic rats. AB - Diabetic encephalopathy is a recognized complication of untreated diabetes resulting in a progressive cognitive impairment accompanied by modification of hippocampal function. The purinergic system is a promising novel target to control diabetic encephalopathy since it might simultaneously control hippocampal synaptic plasticity and glucose handling. We now tested whether streptozotocin induced diabetes led to a modification of extracellular ATP homeostasis and density of membrane ATP (P2) receptors in the hippocampus, a brain structure involved in learning and memory. The extracellular levels of ATP, evaluated in the cerebrospinal fluid, were reduced by 60.4+/-17.0% in diabetic rats. Likewise, the evoked release of ATP as well as its extracellular catabolism was also decreased in hippocampal nerve terminals of diabetic rats by 52.8+/-10.9% and 38.7+/-6.5%, respectively. Western blot analysis showed that the density of several P2 receptors (P2X(3,5,7) and P2Y(2,6,11)) was decreased in hippocampal nerve terminals. This indicates that the synaptic ATP signaling is globally depressed in diabetic rats, which may contribute for diabetes-associated decrease of synaptic plasticity. In contrast, the density of P2 receptors (P2X(1,2,5,6,7) and P2Y(6) but not P2Y(2)) increased in whole hippocampal membranes, suggesting an adaptation of non-synaptic P2 receptors to sense decreased levels of extracellular ATP in diabetic rats, which might be aimed at preserving the non synaptic purinergic signaling. PMID- 17869436 TI - Potentiation of the nicotinic acetylcholine receptor by aluminum in mammalian neurons. AB - Aluminum (Al(3+)), a known neurotoxic substance, has long been implicated in the pathogenesis of Alzheimer's disease and other neurodegenerative diseases. Al(3+) targets many ligand-gated and voltage-gated ion channels and modulates their functions. In the present study, the actions of Al(3+) on the nicotinic acetylcholine receptor (nAChR) were investigated by whole-cell patch clamp technique in acutely isolated rat trigeminal ganglion neurons. We observed that Al(3+) potentiated nicotine-evoked inward currents in a concentration-dependent manner (10-1000 microM). The effects of Al(3+) on nicotine-evoked currents were voltage independent. Al(3+) appeared to increase the affinity of nicotine to nAChR but not the efficacy. Al(3+) reduced the agonist concentration producing a half-maximal response (EC(50)) for nicotine from 74.4+/-1.9 microM to 32.9+/-2.6 microM, but did not alter the threshold nor maximal response. On the contrary, another trivalent cation, Ga(3+), had little effect on nicotine-evoked currents. The present results indicated that Al(3+) enhanced the function of nAChR and this potentiation might underlie the neurological alteration induced by Al(3+). PMID- 17869438 TI - Functional changes in the vanilloid receptor subtype 1 channel during and after acute desensitization. AB - Agonist-induced desensitization of the transient receptor potential vanilloid receptor-1 (TRPV1) is one of the key strategies that offer a way to alleviate neuropathic and inflammatory pain. This process is initiated by TRPV1 receptor activation and the subsequent entry of extracellular Ca(2+) through the channel into sensory neurones. One of the prominent mechanisms responsible for TRPV1 desensitization is dephosphorylation of the TRPV1 protein by the Ca(2+)/calmodulin-dependent enzyme, phosphatase 2B (calcineurin). Of several consensus phosphorylation sites identified so far, the most notable are two sites for Ca(2+)/calmodulin dependent kinase II (CaMKII) at which the dynamic equilibrium between the phosphorylated and dephosphorylated states presumably regulates agonist binding. We examined the mechanisms of acute Ca(2+)-dependent desensitization using whole-cell patch-clamp techniques in human embryonic kidney (HEK) 293T cells expressing the wild type or CaMKII phosphorylation site mutants of rat TRPV1. The nonphosphorylatable mutant S502A/T704I was capsaicin insensitive but the S502A/T704A construct was fully functional, indicating a requirement for a specific residue at position 704. A point mutation at the nearby conserved residue R701 strongly affected the heat, capsaicin and pH-evoked currents. As this residue constitutes a stringent CaMKII consensus site but is also predicted to be involved in the interaction with membrane phosphatidylinositol 4,5-bisphosphate (PIP(2)), these data suggest that in addition to dephosphorylation, or as its consequence, a short C-terminal juxtamembrane segment adjacent to the transient receptor potential box composed of R701 and T704 might be involved in the decelerated gating kinetics of the desensitized TRPV1 channel. PMID- 17869437 TI - 5-HT(2) receptor subtypes mediate different long-term changes in GABAergic activity to parasympathetic cardiac vagal neurons in the nucleus ambiguus. AB - Serotonin (5-HT), and in particular 5-HT(2) receptors, play an important role in cardiorespiratory function within the brainstem. In addition, abnormalities in the 5-HT system have been implicated in many cardiorespiratory disorders, including sudden infant death syndrome. However, little is known about the mechanisms of action of 5-HT(2) receptors in altering the activity of parasympathetic cardiac neurons in the brainstem. In this study we examined the effects of activation of different subtypes of 5-HT(2) receptors on spontaneous and respiratory-evoked GABAergic neurotransmission to cardioinhibitory vagal neurons within the nucleus ambiguus as well as rhythmic fictive inspiratory related activity in rats. A single application of alpha-Me-5-hydroxytryptamine maleate (alpha-Me-5-HT), a 5-HT(2) receptor agonist, did not significantly alter the frequency of spontaneous or respiratory-evoked GABAergic inhibitory postsynaptic currents (IPSCs) in cardiac vagal neurons. However, repetitive successive applications of alpha-Me-5-HT elicited a long-lasting (>/=1 h) decrease in the frequency of spontaneous as well as inspiratory-related GABAergic IPSCs to cardiac vagal neurons. This study demonstrates multiple, but not single applications of the 5-HT(2) receptor agonist alpha-Me-5-HT caused a long-lasting inhibition of both spontaneous and fictive inspiratory-related GABAergic neurotransmission to CVNs, which can be prevented by the 5-HT(2B) receptor antagonist SB204741, but persisted with the 5-HT(2A/2C) receptor antagonist ketanserin. The 5-HT(2) receptor agonist alpha-Me-5-HT also reversibly and transiently excited central fictive inspiratory activity, which was abolished by ketanserin, but was unaffected by the 5-HT(2B) receptor antagonist SB204741. PMID- 17869439 TI - Role of inhibitor of apoptosis protein in gentamicin-induced cochlear hair cell damage. AB - Apoptotic cell death is considered to play a key role in gentamicin-induced cochlear hair cell loss. Inhibitor of apoptosis proteins (IAPs) are important regulators of apoptosis that can prevent activation of effector caspases. This study was designed to investigate the possible involvement of X-linked inhibitor of apoptosis protein (XIAP) in hair cell death due to gentamicin. Basal turn organ of Corti explants from postnatal day (p) p3 or p4 rats were maintained in tissue culture and were exposed to 35 muM gentamicin for up to 48 h. Effects of specific XIAP inhibitors on gentamicin-induced hair cell loss and caspase-3 activation were examined. XIAP inhibitors increased gentamicin-induced hair cell loss but an inactive analog had no effect. Caspase-3 activation was primarily observed at 36 or 48 h in gentamicin-treated hair cells, whereas caspase-3 activation peaked at 24-36 h when explants were treated with gentamicin and an XIAP inhibitor. The inhibitors alone had no effect on hair cells. Finally, a caspase-3 inhibitor decreased caspase-3 activation and hair cell loss induced by gentamicin and an XIAP inhibitor, but caspase-8 and -9 inhibitors did not. The results indicate that XIAP normally acts to decrease caspase-3 activation and hair cell loss during gentamicin ototoxicity, as part of a protective response to potentially damaging stimuli. PMID- 17869440 TI - Detection and differentiation of sensorineural hearing loss in mice using auditory steady-state responses and transient auditory brainstem responses. AB - Sensorineural hearing loss (SNHL) comprises hearing disorders with diverse pathologies of the inner ear and the auditory nerve. To date, an unambiguous phenotypical characterization of the specific pathologies in an affected individual remains impossible. Here, we evaluated the use of scalp-recorded auditory steady-state responses (ASSR) and transient auditory brainstem responses (ABR) for differentiating the disease mechanisms underlying sensorineural hearing loss in well-characterized mouse models. We first characterized the ASSR evoked by sinusoidally amplitude-modulated tones in wild-type mice. ASSR were robustly elicited within three ranges of modulation frequencies below 200 Hz, from 200 to 600 Hz and beyond 600 Hz in most recordings. Using phase information we estimated the apparent ASSR latency to be about 3 ms, suggesting generation in the auditory brainstem. Auditory thresholds obtained by automated and visual analysis of ASSR recordings were comparable to those found with tone-burst evoked ABR in the same mice. We then recorded ASSR and ABR from mouse mutants bearing defects of either outer hair cell amplification (KCNQ4-knockout) or inner hair cell synaptic transmission (Bassoon-mutant). Both mutants showed an increase of ASSR and ABR thresholds of approximately 40 dB versus wild-type when investigated at 8 weeks of age. Mice with defective amplification displayed a steep rise of ASSR and ABR amplitudes with increasing sound intensity, presumably reflecting a strong recruitment of synchronously activated neural elements beyond threshold. In contrast, the amplitudes of ASSR and ABR responses of mice with impaired synaptic transmission grew very little with sound intensity. In summary, ASSR allow for a rapid, objective and frequency-specific hearing assessment and together with ABR and otoacoustic emissions can contribute to the differential diagnosis of SNHL. PMID- 17869441 TI - The 5-HT7 receptor: role in novel object discrimination and relation to novelty seeking behavior. AB - Despite showing high affinity for neuroleptics and hallucinogens, the function of the 5-HT7 receptor in cognition remains largely speculative. This study tests the hypothesis that 5-HT7 participates in gauging salience of novel visual stimuli as a function of the animal's initial tendency for novelty-seeking. Novelty-seeking behavior in the rat is thought to model some aspects of sensation-seeking in humans, a personality trait closely associated to drug abuse. We analyzed the effects of the 5-HT7 receptor antagonist SB269.970 (3 mg kg(-1) or 15 mg kg(-1) i.p.) on object-recognition tasks using rats that differed in exploration of novel environments, namely high (HR) and low (LR) responders. The task involved a first encounter with an object ("old"), which after a delay of 3 h had to be discriminated from a different object ("new"). The antagonist was injected into HR and LR rats immediately after the first encounter with the objects and its effects on recall of objects were evaluated. In the absence of drug, LR but not HR rats were able to discriminate the familiarity of previously encountered objects. A low dose (3 mg kg(-1)) of SB269.970 was ineffective in altering object discrimination. A higher dose (15 mg kg(-1)) inhibited novel-object exploration in LR animals thus curtailing differences in object recognition, a finding that was replicated. In order to validate our studies, the effects of the cholinergic muscarinic antagonist scopolamine (0.2 mg kg(-1), i.p.) on object recognition were also evaluated in one of the cohorts 2 weeks after the first NOD experiment. In the Choice phase, all vehicle-treated rats succeeded in recognizing the new object. Scopolamine inhibited object discrimination in HR rats more efficiently than it did in LR rats. Taken together, these results suggest that 5-HT7 may mediate attentional and memory processes relevant to novelty-induced arousal. PMID- 17869442 TI - Characteristics of sensori-motor interaction in the primary and secondary somatosensory cortices in humans: a magnetoencephalography study. AB - We studied sensori-motor interaction in the primary (SI) and secondary somatosensory cortex (SII) using magnetoencephalography. Since SII in both hemispheres was activated following unilateral stimulation, we analyzed SIIc (contralateral to stimulation) as well as SIIi (ipsilateral to stimulation). Four tasks were performed in human subjects in which a voluntary thumb movement of the left or right hand was combined with electrical stimulation applied to the index finger of the left or right hand: L(M)-L(S) (movement of the left thumb triggered stimulation to the left finger), L(M)-R(S) (movement of the left thumb triggered electrical stimulation to the right finger), R(M)-R(S) (movement of the right thumb triggered electrical stimulation to the right finger), and R(M)-L(S) (movement of the right thumb triggered electrical stimulation to the left finger). Stimulation to the index finger only (S condition) was also recorded. In SI, the amplitude of N20m and P35m was significantly attenuated in the R(M)-R(S) and L(M)-L(S) tasks compared with the S condition, but that for other tasks showed no change, corresponding to a conventional gating phenomenon. In SII, the R(M)-L(S) task significantly enhanced the amplitude of SIIc but reduced that of SIIi compared with the S condition. The L(M)-L(S) and R(M)-R(S) tasks caused a significant enhancement only in SIIi. The L(M)-R(S) task enhanced the amplitude only in SIIc. The laterality index showed that SII modulation with voluntary movement was more dominant in the hemisphere ipsilateral to movement but was not affected by the side of stimulation. These results provided the characteristics of activities in somatosensory cortices, a simple inhibition in SI but complicated changes in SII depending on the side of movement and stimulation, which may indicate the higher cognitive processing in SII. PMID- 17869443 TI - Nerve growth factor neuroprotection of ethanol-induced neuronal death in rat cerebral cortex is age dependent. AB - Organotypic cultures of rat cortex were used to test the hypotheses that nerve growth factor (NGF) is neuroprotective for immature cortical neurons and that ethanol abolishes this neuroprotection in a developmental stage-dependent manner. Samples were obtained on gestational day (G) 16 or postnatal day (P) 3 and cultured with ethanol (0 or 400 mg/dl) and NGF (0 or 30 ng/ml) for 72 h. Dying neurons were identified as exhibiting terminal nick-end labeling, immunoreactivity for activated caspase 3, or condensed nuclear chromatin. Two cortical compartments were examined in fetal tissue: a superficial, cell-sparse marginal zone (MZ) and a cell-dense cortical plate (CP). At P3, the CP was subdivided into a cell-dense upper cortical plate (UCP) and a less densely packed lower cortical plate (LCP). Neuronal death in the MZ was affected by neither NGF nor ethanol at both ages. In the fetal CP, NGF did not affect the incidence of cell death, but ethanol increased it. Treatment with NGF caused an upregulation of the expression of Neg, a gene known to be affected by NGF and ethanol. NGF did not ameliorate the ethanol-induced death. In pups, ethanol increased the amount of death in the LCP. NGF did protect against this death. Neither ethanol nor NGF altered the incidence of cell death in the UCP. The laminar-dependent neuroprotection did not correlate with expression of NGF receptors or Neg. Thus, NGF can be protective against the neurotoxic effect of ethanol in the neonatal brain. This effect is site selective and time dependent and it targets postmigratory, differentiating neurons. PMID- 17869444 TI - Kv1.1/1.2 channels are downstream effectors of nitric oxide on synaptic GABA release to preautonomic neurons in the paraventricular nucleus. AB - The paraventricular nucleus (PVN) of the hypothalamus is important for the neural regulation of cardiovascular function. Nitric oxide (NO) increases synaptic GABA release to presympathetic PVN neurons through the cyclic guanosine monophosphate (cGMP)/protein kinase G signaling pathway. However, the downstream signaling mechanisms underlying the effect of NO on synaptic GABA release remain unclear. In this study, whole-cell voltage-clamp recordings were performed on retrograde labeled spinally projecting PVN neurons in rat brain slices. Bath application of the NO precursor l-arginine or the NO donor S-nitroso-N-acetylpenicillamine (SNAP) significantly increased the frequency of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) in labeled PVN neurons. A specific antagonist of cyclic ADP ribose, 8-bromo-cyclic ADP ribose (8-Br-cADPR), had no significant effect on l-arginine-induced potentiation of mIPSCs. Surprisingly, blocking of voltage-gated potassium channels (Kv) with 4-aminopyridine or alpha-dendrotoxin eliminated the effect of l-arginine on mIPSCs in all labeled PVN neurons tested. The membrane permeable cGMP analog mimicked the effect of l-arginine on mIPSCs, and this effect was blocked by alpha-dendrotoxin. Furthermore, the specific Kv channel blocker for Kv1.1 (dendrotoxin-K) or Kv1.2 (tityustoxin-Kalpha) abolished the effect of l-arginine on mIPSCs in all neurons tested. SNAP failed to inhibit the firing activity of labeled PVN neurons in the presence of dendrotoxin-K, Kalpha. Additionally, the immunoreactivity of Kv1.1 and Kv1.2 subunits was colocalized extensively with synaptophysin in the PVN. These findings suggest that NO increases GABAergic input to PVN presympathetic neurons through a downstream mechanism involving the Kv1.1 and Kv1.2 channels at the nerve terminals. PMID- 17869445 TI - Adaptive radiotherapy for prostate cancer using kilovoltage cone-beam computed tomography: first clinical results. AB - PURPOSE: To evaluate the first clinical results of an off-line adaptive radiotherapy (ART) protocol for prostate cancer using kilovoltage cone-beam computed tomography (CBCT) in combination with a diet and mild laxatives. METHODS AND MATERIALS: Twenty-three patients began treatment with a planning target volume (PTV) margin of 10 mm. The CBCT scans acquired during the first six fractions were used to generate an average prostate clinical target volume (AV CTV), and average rectum (AV-Rect). Using these structures, a new treatment plan was generated with a 7-mm PTV margin. Weekly CBCT scans were used to monitor the CTV coverage. A diet and mild laxatives were introduced to improve image quality and reduce prostate motion. RESULTS: Twenty patients were treated with conform ART protocol. For these patients, 91% of the CBCT scans could be used to calculate the AV-CTV and AV-Rect. In 96% of the follow-up CBCT scans, the CTV was located within the average PTV. In the remaining 4%, the prostate extended the PTV by a maximum of 1 mm. Systematic and random errors for organ motion were reduced by a factor of two compared with historical data without diet and laxatives. An average PTV reduction of 29% was achieved. The volume of the AV Rect that received >65 Gy was reduced by 19%. The mean dose to the anal wall was reduced on average by 4.8 Gy. CONCLUSIONS: We safely reduced the high-dose region by 29%. The reduction in irradiated volume led to a significant reduction in the dose to the rectum. The diet and laxatives improved the image quality and tended to reduce prostate motion. PMID- 17869446 TI - Preoperative chemoradiotherapy for rectal cancer: randomized trial comparing oral uracil and tegafur and oral leucovorin vs. intravenous 5-fluorouracil and leucovorin. AB - PURPOSE: To compare, in a randomized trial, 5-fluorouracil (FU) plus leucovorin (LV) (FU+LV) vs. oral uracil and tegafur (UFT) plus LV (UFT+LV) given concomitantly with preoperative irradiation in patients with cT3-4 or N+ rectal cancer. METHODS AND MATERIALS: A total of 155 patients were entered onto the trial. Patients received pelvic radiotherapy (4500-5,040 cGy in 5 to 6 weeks) and chemotherapy consisting of two 5-day courses of 20 mg/m(2)/d LV and 350 mg/m(2)/d FU in the first and fifth weeks of radiotherapy (77 patients) or one course of 25 mg/d oral LV and 300 mg/m(2)/d UFT for 4 weeks beginning in the second week of radiotherapy (78 patients). The primary endpoints were pathologic complete response (pCR) and resectability rate. Secondary endpoints included downstaging rate, toxicity, and survival. RESULTS: Grade 3-5 acute hematologic toxicity occurred only with FU+LV (leukopenia 9%; p = 0.02). There were no differences in resectability rates (92.1% vs. 93.4%; p = 0.82). The pCR rate was 13.2% in both arms. Tumor downstaging was more frequent with UFT+LV (59.2% vs. 43.3%; p = 0.04). Three-year overall survival was 87% with FU+LV and 74% with UFT+LV (p = 0.37). The 3-year cumulative incidences of local recurrence were 7.5% and 8.9%, respectively (p = 0.619; relative risk, 1.46; 95% confidence interval 0.32-6.55). CONCLUSION: Although this study lacked statistical power to exclude clinically significant differences between both groups, the outcome of patients treated with UFT+LV did not differ significantly from that of patients treated with FU+LV, and hematologic toxicity was significantly lower in the experimental arm. PMID- 17869447 TI - Retrospective analysis of locally advanced noninflammatory breast cancer from Chennai, South India, 1990-1999. AB - PURPOSE: This was a retrospective observational study to elicit the outcome of the therapeutic strategy of concurrent neoadjuvant chemoradiotherapy protocol for locally advanced breast cancer. METHODS AND MATERIALS: A large series of 1,117 consecutive cases of locally advanced breast cancer treated at the Cancer Institute (WIA), in Chennai, South India, between 1990 and 1999 and followed through 2004 formed the basis for this study. Disease-free survival was the main outcome, and nodal and tumor downstaging were the intermediate outcome measures studied. RESULTS: Primary tumor downstaging was observed in 45% and nodal downstaging in 57.5%. The disease-free survival rate of nodal downstaged patients at 5, 10, and 15 years was 75%, 65%, and 58%, respectively. The corresponding rates for pre- and postoperative node-negative patients were 70%, 60%, and 59%. The best survival was seen among those who were tumor and node negative postoperatively. Nodal downstaging halved the risk of disease recurrence and death compared with node positivity, irrespective of tumor sterility. CONCLUSIONS: A randomized trial using cyclophosphamide, methotrexate, and 5 fluorouracil vs. an anthracycline-based regimen in the setting of concurrent chemoradiotherapy appears indicated. Additional preoperative chemotherapy to maximize nodal and tumor downstaging should be investigated. A change in postoperative chemotherapy according to nodal status could also be explored. PMID- 17869448 TI - A phase III, double-blind, placebo-controlled prospective randomized clinical trial of d-threo-methylphenidate HCl in brain tumor patients receiving radiation therapy. AB - PURPOSE: The quality of life (QOL) and neurocognitive function of patients with brain tumors are negatively affected by the symptoms of their disease and brain radiation therapy (RT). We assessed the effect of prophylactic d-threo methylphenidate HCl (d-MPH), a central nervous system (CNS) stimulant on QOL and cognitive function in patients undergoing RT. METHODS AND MATERIALS: Sixty-eight patients with primary or metastatic brain tumors were randomly assigned to receive d-MPH or placebo. The starting dose of d-MPH was 5 mg twice daily (b.i.d.) and was escalated by 5 mg b.i.d. to a maximum of 15 mg b.i.d. The placebo was administered as one pill b.i.d. escalating three pills b.i.d. The primary outcome was fatigue. Patients were assessed at baseline, the end of radiation therapy, and 4, 8, and 12 weeks after brain RT using the Functional Assessment of Cancer Therapy with brain and fatigue (FACIT-F) subscales, as well as the Center for Epidemiologic Studies Scale and Mini-Mental Status Exam. RESULTS: The Mean Fatigue Subscale Score at baseline was 34.7 for the d-MPH arm and 33.3 for the placebo arm (p = 0.61). At 8 weeks after the completion of brain RT, there was no difference in fatigue between patient groups. The adjusted least squares estimate of the Mean Fatigue Subscale Score was 33.7 for the d-MPH and 35.6 for the placebo arm (p = 0.64). Secondary outcomes were not different between the two treatment arms. CONCLUSIONS: Prophylactic use of d-MPH in brain tumor patients undergoing RT did not result in an improvement in QOL. PMID- 17869449 TI - Immunosuppressive total lymphoid irradiation-based reconditioning regimens enable engraftment after graft rejection or graft failure in patients treated with allogeneic hematopoietic stem cell transplantation. AB - PURPOSE: To retrospectively evaluate the efficacy of total lymphoid irradiation (TLI)-based reconditioning regimens in patients with graft failure or graft rejection after allogeneic hematopoietic stem cell transplantation. METHODS AND MATERIALS: The results of 14 patients (7 adults and 7 children) with a variety of hematologic malignant diseases treated with a TLI-based reconditioning regimen with 7-Gy single-dose application plus anti-T-lymphocyte antibody OKT3 (n = 11) and/or antithymocyte globulin (n = 7)/fludarabine (n = 9), followed by an infusion of peripheral blood stem cells (n = 13) or bone marrow stem cells (n = 1) from related or unrelated donors, were retrospectively analyzed. RESULTS: Of the 14 recipients, the data from 11 were evaluable for engraftment after TLI based reconditioning because 3 adults died early (at Day 2, 5, and 15) after the second transplantation of infectious complications. Engraftment in 4 adults was seen after a median of 12 days (range, 10-18) and occurred after a median of 10 days (range, 9-32) in the 7 children. TLI-based reconditioning was well-tolerated with no severe toxicity. The median overall survival and disease-free survival for the whole cohort was 140 days (range, 5-1,268). After a median follow-up of 681 days, the disease-free survival and overall survival rate was 85.7% and 85.7%, respectively, in the children. Despite engraftment in the 4 remaining adults, 1 died of fatal graft-vs.-host disease, 1 of infectious complications, 1 of disease relapse, and 1 of acute respiratory distress syndrome. CONCLUSIONS: In patients with graft failure or graft rejection after allogeneic hematopoietic stem cell transplantation, TLI-based reconditioning regimens allow sustained engraftment, paralleled by a favorable toxicity profile, potentially leading to long-term survival. PMID- 17869450 TI - Influence of FDG-PET on computed tomography-based radiotherapy planning for locally recurrent nasopharyngeal carcinoma. AB - PURPOSE: Assuming F-18-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET)/computed tomography (CT) to be more accurate in representing the true disease extent than CT alone, we prospectively designed this study to evaluate how the addition of FDG-PET influences CT-based radiotherapy planning for locally recurrent nasopharyngeal carcinoma. PATIENTS AND METHODS: All patients underwent FDG-PET/CT simulation scans. For each patient, the gross tumor volume (GTV) was separately delineated with or without the addition of PET information and defined as GTV PET/CT and GTV CT, respectively. Corresponding planning target volumes (PTV) were generated for the GTV CT (PTV(CT)) and GTV PET/CT (PTV PET/CT). Three dimensional conformal radiotherapy plans were separately created for PTV CT and PTV PET/CT. To assess the potential geographic miss of the PET/CT-based disease in CT-based treatment planning, the size and location of the GTV PET/CT, PTV(PET/CT), and PTV(CT) were analyzed, and the three-dimensional conformal radiotherapy plans created using the PTV CT were evaluated with the GTV PET/CT and PTV PET/CT information. RESULTS: A total of 43 patients were enrolled in this study. Distant metastasis was found in 4 patients with the addition of the PET information. The 39 patients without distant metastasis proceeded to three dimensional conformal radiotherapy planning. Inadequate coverage of the GTV PET/CT and PTV PET/CT by the PTV CT occurred in 7 (18%) and 20 (51%) patients, respectively. This resulted in <95% of the GTV(PET/CT) and PTV PET/CT receiving >or=95% of the prescribed dose in 4 (10%) and 13 (33%) patients, respectively. CONCLUSIONS: The addition of FDG-PET information might influence CT-based radiotherapy planning for locally recurrent nasopharyngeal carcinoma by altering the definition of the target volume, with the potential to avoid a geographic miss of true disease. PMID- 17869452 TI - Larvicidal and growth inhibition of the malaria vector Anopheles stephensi by triterpenes from Dysoxylum malabaricum and Dysoxylum beddomei. AB - Secondary metabolites from Dysoxylum malabaricum and Dysoxylum beddomei were tested against mature and immature stage of the mosquito vector Anopheles stephensi under laboratory conditions. The triterpenes 3beta,24,25 trihydroxycycloartane and beddomeilactone from D. malabaricum and D. beddomei showed strong larvicidal, pupicidal and adulticidal activity. They also affected the reproductive potential of adults by acting as oviposition deterrents. The highest concentration tested (10 ppm) of both compounds evoked more than 90% mortality and oviposition deterrence. PMID- 17869451 TI - Comparison of treatment tolerance and outcomes in patients with cervical cancer treated with concurrent chemoradiotherapy in a prospective randomized trial or with standard treatment. AB - PURPOSE: To compare the treatment and outcomes of cervical cancer patients treated with concurrent chemoradiotherapy (CT-RT) in a multi-institutional trial or as standard care. PATIENTS AND METHODS: We reviewed the records of 302 patients treated with CT-RT for locoregionally confined, intact cervical cancer between 1990 and 2005. Of the 302 patients, 76 were treated using cisplatin and 5 fluorouracil (C/F) on Radiation Therapy Oncology Group protocol 90-01 (CT-RT(90 01)); 226 underwent CT-RT as standard care with either C/F [CT-RT(SC(C/F)); n = 115] or weekly cisplatin [CT-RT(SC(WC)); n = 111). RESULTS: The CT-RT(90-01) patients more often had tumors >or=6 cm and were less often diabetic than were the CT-RT(SC) patients. The CT-RT(SC(WC)) patients were more likely than the CT RT(SC(C/F)) patients to be >or=60 years old or to have Stage III-IV disease. During treatment, CT-RT(SC(C/F)) patients experienced more Grade 2-3 neutropenia and were, therefore, less likely to receive 200 mg/m(2) cisplatin than were either CT-RT(SC(WC)) or CT-RT(90-01) patients (52% vs. 77% vs. 85%, respectively; p <0.001). At 5 years, the disease-specific survival rates were greater for patients treated with C/F [CT-RT(SC(C/F)), 75%; CT-RT(90-01), 79%] than for those treated with CT-RT(SC(WC)) (58%; p = 0.02). On multivariate analysis, C/F chemotherapy, cisplatin dose >or=200 mg/m(2), Stage I-II disease, and negative pelvic lymph nodes were independent predictors of improved disease-specific survival. CONCLUSIONS: Even within a large comprehensive cancer center, the high rates of chemotherapy completion achieved on a multi-institutional trial can be difficult to reproduce in standard practice. Although C/F toxicity was greater in the standard care patients, their outcomes were similar to those of patients treated with C/F on Radiation Therapy Oncology Group protocol 90-01. PMID- 17869453 TI - The initiation of eukaryotic and prokaryotic protein synthesis: a selective accessibility and multisubstrate enzyme reaction. AB - An extension of our unique accessibility hypothesis for the initiation of protein synthesis is proposed following a review of the initiation of protein synthesis. The E. coli model initiation sequence generated by computer from 68 initiation sequences and the eukaryotic consensus initiation sequence derived by non computer analysis of 211 initiation sequences do not contain a specific base in any position; they are only assigned preferred bases. The initiation site, in other words, is a varied sequence of preferred bases and its sequence is non unique. This indicates that the ribosomal recognition of the initiation site may be the result of multiple interactions that are cooperative and cumulative and typical of multisubstrate enzymes. Because of this characteristic, the model of multisubstrate enzymes with broad substrate specificity is proposed as a paradigm for the initiation of protein synthesis. As predicted by this model, changes in the leader and downstream sequences that improve the agreement with the preferred base sequence do indeed enhance the rate of protein synthesis. The eukaryotic/prokaryotic hybrid studies show a considerable overlap in the specificities of the two groups of ribosomes. The scanning of the mRNA from the 5'-end postulated by the scanning hypothesis is not a necessary step since eukaryotic ribosomes are able to bind to internal mRNA sites and initiate synthesis. Our unique accessibility hypothesis, which is extended by coupling cooperative and cumulative specificity in ribosomal function, is referred to for brevity as the cumulative specificity hypothesis. The hypothesis actually postulates a selective accessibility and cooperative-cumulative specificity mechanism; it is able to account for the behavior of both eukaryotic and prokaryotic initiation of protein synthesis. From another perspective, the hypothesis can be regarded as providing a mechanism that enables ribosomes to recognize the IS in the absence of a unique initiation sequence. PMID- 17869454 TI - Serological evidence of continuing high Usutu virus (Flaviviridae) activity and establishment of herd immunity in wild birds in Austria. AB - Usutu virus (USUV), family Flaviviridae, has been responsible for avian mortality in Austria from 2001 to 2006. The proportion of USUV-positive individuals among the investigated dead birds decreased dramatically after 2004. To test the hypothesis that establishment of herd immunity might be responsible, serological examinations of susceptible wild birds were performed. Blood samples of 442 wild birds of 55 species were collected in 4 consecutive years (2003--2006). In addition, 86 individuals from a birds of prey rehabilitation centre were bled before, at the peak, and after the 2005 USUV transmission season in order to identify titre dynamics and seroconversions. The haemagglutination inhibition test was used for screening and the plaque reduction neutralization test for confirmation. While in the years 2003 and 2004 the proportion of seropositive wild birds was <10%, the percentage of seroreactors raised to >50% in 2005 and 2006. At the birds of prey centre, almost three quarters of the owls and raptors exhibited antibodies before the 2005 transmission season; this percentage dropped to less than half at the peak of USUV transmission and raised again to almost two thirds after the transmission season. These data show a from year to year continuously increasing proportion of seropositive wild birds. The owl and raptor data indicate significant viral exposure in the previous season(s), but also a number of new infections during the current season, despite the presence of antibodies in some of these birds. Herd immunity is a possible explanation for the significant decrease in USUV-associated bird mortalities in Austria during the recent years. PMID- 17869455 TI - Detection and quantification of classical swine fever virus in air samples originating from infected pigs and experimentally produced aerosols. AB - During epidemics of classical swine fever (CSF), neighbourhood infections occurred where none of the 'traditional' routes of transmission like direct animal contact, swill feeding, transport contact or transmission by people could be identified. A hypothesized route of virus introduction for these herds was airborne transmission. In order to better understand this possible transmission route, we developed a method to detect and quantify classical swine fever virus (CSFV) in air samples using gelatine filters. The air samples were collected from CSFV-infected pigs after experimental aerosolization of the virus. Furthermore, we studied the viability of the virus with time in aerosolized state. Three strains of CSFV were aerosolized in an empty isolator and air samples were taken at different time intervals. The virus remained infective in aerosolized state for at least 30 min with half-life time values ranging from 4.5 to 15 min. During animal experiments, concentrations of 10(0.3)-10(1.6)TCID(50)/m(3) CSFV were detected in air samples originating from the air of the pig cages and 10(0.4) 10(4.0)TCID(50)/m(3) from the expired air of infected animals. This is the first study describing the isolation and quantification of CSFV from air samples originating from infected pigs and their cages, supporting previous findings that airborne transmission of CSF is feasible. PMID- 17869456 TI - Simultaneous detection and differentiation of Newcastle disease and avian influenza viruses using oligonucleotide microarrays. AB - Newcastle disease (ND) and avian influenza (AI) are two of the most important zoonotic viral diseases of birds throughout the world. These two viruses often have a great impact upon the poultry industry. Both viruses are associated with transmission from wild to domestic birds, and often display similar signs that need to be differentiated. A rapid surveillance among wild and domestic birds is important for early disease detection and intervention, and is the basis for what measures should be taken. The surveillance, thus, should be able to differentiate the diseases and provide a detailed analysis of the virus strains. Here, we described a fast, simultaneous and inexpensive approach to the detection of Newcastle disease virus (NDV) and avian influenza virus (AIV) using oligonucleotide microarrays. The NDV pathotypes and the AIV haemagglutinin subtypes H5 and H7 were determined at the same time. Different probes on a microarray targeting the same gene were implemented in order to encompass the diversified virus strains or provide multiple confirmations of the genotype. This ensures good sensitivity and specificity among divergent viruses. Twenty-four virus isolates and twenty-four various combinations of the viruses were tested in this study. All viruses were successfully detected and typed. The hybridization results on microarrays were clearly identified with the naked eyes, with no further imaging equipment needed. The results demonstrate that the detection and typing of multiple viruses can be performed simultaneously and easily using oligonucleotide microarrays. The proposed method may provide potential for rapid surveillance and differential diagnosis of these two important zoonoses in both wild and domestic birds. PMID- 17869457 TI - The advantage of polymer addition to a non-ionic oil in water microemulsion for the dermal delivery of progesterone. AB - The influence of progesterone on the physicochemical behaviour of the o/w microemulsion consisting of the non-ionic surfactant polyoxyethylene-10-dodecyl ether, tributyrin and water was investigated. Thereby no significant influence could be detected in terms of droplet size, zeta potential, conductivity and pH by progesterone. However the chemical stability of progesterone was insufficient during the storage of 6 months. Therefore, two different polymeric agents, named silicon dioxide and polymeric emulsifier, were added to the progesterone containing microemulsions. These polymers increased the chemical stability of progesterone significantly. Moreover the polymeric additives improved the skin permeation 1.24- and 1.63-fold and decreased the skin retention in relation to the pure microemulsion. The polymer-stabilized progesterone microemulsions are interesting vehicles for skin application of progesterone. PMID- 17869458 TI - Cremophor-free intravenous microemulsions for paclitaxel II. Stability, in vitro release and pharmacokinetics. AB - Two cremophor-free microemulsion systems LBMW (lecithin:butanol:myvacet:water) and CMW (capmul:myvacet:water), for intravenous (IV) administration of paclitaxel (PAC) were previously developed and characterized. Their chemical stability, in vitro release and pharmacokinetics of PAC were assessed using Taxol (cremophor:ethanol 1:1, 6 mg/ml) as a reference. The shelf-lives of PAC at 25 degrees C in Taxol, LBMW and CMW, in an accelerated stability study, were 71, 57 and 31 days, respectively. The activation energy (Ea) for PAC in Taxol, LBMW and CMW was 23, 16 and 14 kcal/mol, respectively. PAC released from LBMW and CMW using a dialysis technique was significantly slower than that from Taxol. The extents of release of PAC from LBMW and CMW were 25 and 50% of that from Taxol. In vivo pharmacokinetic studies in male Sprague-Dawley rats after IV administration revealed that PAC in LBMW and CMW remained in the systemic circulation five and two times longer and was eight and three times more widely distributed than PAC from Taxol. LBMW and CMW offer a significant clinical advantage in terms of the prolonged half-life and wide tissue distribution, indicating that PAC delivered by these systems intravenously may result in prolonged exposure of PAC to the tumor and subsequently an improved clinical efficacy. PMID- 17869459 TI - Cremophor-free intravenous microemulsions for paclitaxel I: formulation, cytotoxicity and hemolysis. AB - Two cremophor-free microemulsions, lecithin:butanol:myvacet oil:water (LBMW) and capmul:myvacet oil:water (CMW) for paclitaxel (PAC) were developed for intravenous (i.v.) administration. Six surfactants and four oils were screened with various combinations for maximal water incorporation and PAC solubility. Microemulsion regions were subsequently determined in ternary phase diagrams. Cytotoxicity in an MDA-M231 human breast cancer cell line and hemolytic potential were assessed in these systems compared to Taxol (cremophor EL:ethanol, 1:1, 6 mgPAC/ml). The maximal water incorporation into the lecithin:butanol surfactant blend was greater than that incorporated into capmul when combined with the oils screened. PAC solubility in myvacet oil was increased 1389-fold over its aqueous solubility. LBMW had a larger microemulsion region (46.5% of total ternary phase diagram) than that seen with CMW (18.6%). The droplet size of the dispersed phase was 111.5 (4.18)nm for LBMW and 110.3 (8.09)nm for CMW. Cytotoxicity of PAC was in decreasing order of: Taxol>LBMW>CMW. The IC50 values for LBMW and CMW ranged from 4.5 to 5.7 and >10 microM, respectively, as compared to that of Taxol (1.3 to 1.8 microM). Eighty-three percent, 68%, and 63% of red blood cells remain unlysed at a formulation volume to blood ratio of 0.035 in LBMW, CMW and Taxol. Promising microemulsions, LBMW and CMW were developed that can incorporate approximately 12 mg/g of PAC, substantially higher than its aqueous solubility (10.8 microg/ml) and that in the Taxol vehicle (6 mg/ml). PAC retained its cytotoxicity in the LBMW and CMW and was less likely to cause hemolysis compared to Taxol. This higher drug loading results in a smaller vehicle volume in required doses of these formulations and potentially less vehicle-related side effects are anticipated. PMID- 17869460 TI - Release profiles and morphological characterization by atomic force microscopy and photon correlation spectroscopy of 99mTechnetium-fluconazole nanocapsules. AB - Several classes of antifungal have been employed in candidiasis treatment, but patients with advanced immunodeficiency can present unsatisfactory results after therapy. In these cases, high doses of drugs or the use of multiple agents are sometimes used, and hence increasing the risk of serious side effects. Considering theses difficulties, the encapsulation of antifungal agents in nanoparticulate carriers has been used with the objective of modifying the pharmacokinetic of drugs resulting in more efficient treatments with less side effects. The purpose of this work was the preparation, characterization and the investigation of the release profiles of radiolabeled fluconazole nanocapsules. The size, homogeneity and zeta potential of NC preparations were determined with a Zetasizer 3000HS. The morphology and the structural organization were evaluated by atomic force microscopy (AFM). The release study in vitro of NC was evaluated in physiologic solution with or without 70% mouse plasma. The labeling yield of fluconazole with 99mTc was 94% and the radiolabeled drug was stable within 24h period. The encapsulation percentage of 99mTc-fluconazole in PLA-POLOX NC and PLA PEG NC was approximately of 30%. The average diameter calculated by photon correlation spectroscopy (PCS) varied from 236 to 356 nm, while the average diameter determined by AFM varied from 238 to 411 nm. The diameter/height relation decreased significantly when 25% glutaraldehyde was used for NC fixation on mica. The zeta potential varied from -55 to -69 nm and surface-modified NC showed lower absolute values than conventional NC. The in vitro release of 99mTc fluconazole in plasma medium of the conventional and surface-modified NC was greater than in saline. The drug release in plasma medium from conventional NC was faster than for surface-modified NC. The results obtained in this work suggest that the nanocapsules containing fluconazole could be used to identify infectious foci, due to the properties, such as size, zeta potential and controlled release of (99m)Tc-fluconazole. The surface-modified nanocapsules could constitute a long-circulating intravenous formulation of fluconazole for treating sepsis caused by disseminated form of candidiasis. However, in vivo studies should be considered and are under investigation. PMID- 17869461 TI - Sinomenine suppresses TNF-alpha-induced VCAM-1 expression in human umbilical vein endothelial cells. AB - Sinomenine (SN), an alkaloid prepared from the root of Sinomenium acutum Rehd. Et wils, is used to alleviate the symptoms of rheumatism in Chinese medicine. In the present study, the potential inhibition of TNF-alpha-induced VCAM-1 expression on human umbilical vein endothelial cells (HUVECs) was evaluated in vitro. HUVECs were isolated from freshly collected umbilical cords. Positive controls were stimulated with TNF-alpha, omitting SN. Negative controls were cultured omitting TNF-alpha and SN. Experimental groups were co-cultured with TNF-alpha and SN at different concentrations (0.25, 0.5, and 1.0 mol/L), or TNF-alpha and Dexamethasone (Dex) at a concentration of 1.0 x 10(-6) mol/L. Cells were harvested after culturing with the above drugs for 12 h. VCAM-1 mRNA expression was detected by real-time quantitative PCR, and VCAM-1 expression was detected by flow cytometry. The experimental data indicated that VCAM-1 mRNA and VCAM-1 were induced by TNF-alpha. The relative VCAM-1 mRNA expression decreased in the experimental groups (p<0.05). Concentrations of SN at 0.5 and 1.0 mol/L inhibited expression of VCAM-1 (p<0.05). SN at concentration of 0.25 mol/L and Dex at concentration of 1.0 x 10(-6) mol/L did not show an inhibitory effect on VCAM-1 expression in TNF-alpha-induced HUVECs. Our preliminary data indicates that SN has an inhibitory effect in vitro on TNF-alpha-induced VCAM-1 expression at both mRNA level and protein level in HUVECs, and suggests that SN may be a novel method of immunotherapy for rheumatic carditis or rheumatic heart disease. PMID- 17869462 TI - Pharmacological analysis of paregoric elixir and its constituents: in vitro and in vivo studies. AB - Paregoric elixir is a phytomedicinal product which is used widely as an analgesic, antispasmodic and antidiarrheal agent. Here, we investigated the pharmacological actions and some of the mechanisms of action of paregoric elixir and compared its action with some of its components, the alkaloids morphine and papaverine. The paregoric elixir given orally to mice did not present relevant toxic effects, even when administered in doses up to 2000-fold higher than those used clinically. However, it showed an antinociceptive action that was more potent, but less efficacious, than morphine. In contrast to morphine, its effect was not dose-dependent and not reversed by the non-selective opioid antagonist naloxone. Moreover, paregoric elixir produced tolerance, but did not cause cross tolerance, with the antinociceptive actions of morphine. When assessed in the gastrointestinal motility in vivo, paregoric elixir elicited graduated reduction of gastrointestinal transit. Finally, like morphine and papaverine, paregoric elixir concentration-dependently inhibited electrically-induced contraction of the guinea pig isolated ileum. In vivo and in vitro gastrointestinal actions of paregoric elixir were not reversed by naloxone. Collectively, the present findings lead us to suggest that the pharmacological actions produced by paregoric elixir are probably due to a synergic action of its constituents. PMID- 17869463 TI - Macroscopic observation of the morphological characteristics of the ammunition gunpowder. AB - At the present time, optical examinations are not used in routine to analyze the gunshot residues, except for the counting and the localization of particles. Indeed, the sequence of examinations often starts immediately with destructive techniques, contrary to the widely accepted law saying that we should progress from general to particular and from non-destructive to destructive and which is recommended for all the fields of forensic sciences. When a cartridge is shot, and before the projectile leaves the gun, all the powder grains should must be completely burnt; however, if this ideal case does not happen, it is possible to find unburnt and/or partially burnt gunpowder particles [H.H. Meng, R. Caddy, Gunshot residue analysis-a review, J. Forensic Sci. 42 (1997) 553-570]. The goal of this paper is to study the morphological characteristics of the powder before and after the shot, to establish if it is possible to determine which type of ammunition has been used on the basis of these characteristics. A set of 181 cartridges of different calibers was considered and various tests carried out to evaluate the technique. On the basis of the observation of the gunpowder particles found on the target, a list of potential cartridges can be established with the actually shot cartridge always found among them. It is important to underline that a maximum of eight cartridges were proposed for each experiment. Consequently, the method can be judged very discriminating. A database was then created, including information related to the morphological characteristics of the gunpowder before and after the shot as well as to the class characteristics of the analysed cartridges. PMID- 17869464 TI - A case of acute disseminated encephalomyelitis presenting with vertigo. AB - We report a 37-year-old woman with acute disseminated encephalomyelitis (ADEM) who presented with progressive vertigo. A central nervous system disorder was initially suspected because gaze-evoked torsional nystagmus was observed and electrical nystagmography (ENG) revealed abnormal eye movements with saccadic ocular pursuit and pathological optokinetic nystagmus. Finally ADEM was diagnosed by the clinical symptoms and the characteristic patterns of brain MRI. It is rare for otolaryngologists to examine patients with ADEM. ADEM takes an acute course and can present a grave state and therefore needs early diagnosis, early treatment. We have to keep ADEM in mind in the diagnosis of vertigo. PMID- 17869465 TI - Hypertonic saline solution stimulated CLC-3 production in primary cultured human nasal epithelial cells. AB - OBJECTIVE: To determine the molecular mechanisms of hypertonic saline on nasal disorders. METHODS: Primary human nasal epithelial cells (HNECs) were treated with 0.9 and 3% saline for 12h. CLC-3 was detected in HNECs by immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting. RESULTS: Positive expression of CLC-3 was detected in HNECs in all subjects by immunohistochemistry. The relative density of CLC-3 mRNA was 0.22+/-0.09 and 0.12+/-0.05 in HNECs treated with 3 and 0.9% saline, respectively. The effect of 3% saline on the expression of CLC-3 in HNECs was observed in a time-dependent manner. CONCLUSIONS: Hypertonic saline decreases the nasal edema and influences the mucocilliary function through the fluid secretion in vitro and may be associated with the upregulation of CLC-3. PMID- 17869466 TI - Magnetic resonance imaging in congenital facial palsy. AB - We report magnetic resonance (MR) findings in a patient with congenital unilateral facial palsy and a patient with atypical Moebius syndrome. MR imaging showed a complete deficiency of right facial nerve in the patient with congenital unilateral facial palsy and bilateral, thin proximal facial nerves in the Moebius syndrome patient. Three-dimensional constructive interference in steady state (3D CISS) MR imaging, especially reconstructions perpendicular to the bilateral internal auditory channel, was very useful when diagnosing patients with facial palsy due to the associated facial nerve abnormalities. PMID- 17869467 TI - Modified Atkins diet therapy for a case with glucose transporter type 1 deficiency syndrome. AB - Glucose transporter type 1 deficiency syndrome (GLUT-1 DS), giving rise to impaired glucose transport across the blood-brain barrier, is characterized by infantile seizures, complex motor disorders, global developmental delay, acquired microcephaly, and hypoglycorrhachia. GLUT-1 DS can be treated effectively with a ketogenic diet because it can provide an alternative fuel for brain metabolism; however, the excessive restriction of food intake involved frequently makes it difficult for patients to initiate or continue the diet. Recently, the modified Atkins diet, which is much less restrictive in terms of the total calorie and protein intake than the classical ketogenic diet, has been shown to be effective and well tolerated in children with intractable epilepsy. We successfully introduced the modified Atkins diet to a 7-year-old boy with GLUT-1 DS, whose caregivers refused ketogenic diet treatment because of strong concerns over restricting the diet. The modified Atkins diet should be considered for patients with GLUT-1 DS as an alternative to the traditional ketogenic diet. PMID- 17869468 TI - Recurrent attacks of status epilepticus as predominant symptom in 3 methylcrotonyl-CoA carboxylase deficiency. AB - A patient with isolated 3-methylcrotonyl-CoA carboxylase (MCC) deficiency with an unusual clinical presentation is described. The patient presented with clusters of seizures with two or three months disease free interval in the first year of life which then evolved into attacks of status epilepticus after the age of 12 months. MCC deficiency was suspected because of elevated C5-OH-carnitine in tandem mass spectrometry and elevated 3-hydroxy-isovaleric acid in urine organic acid analysis. Deficiency of MCC was confirmed in cultured fibroblasts and mutation analysis revealed a novel mutation in MCCB, p.S39F. Attacks of status epilepticus as a predominant symptom have not been described before in isolated MCC deficiency. PMID- 17869469 TI - Reproducibility of CT-based bone texture parameters of cancellous calf bone samples: influence of slice thickness. AB - Bone microarchitecture is an important determinant of the fracture risk, independently of bone mineral density. At present, bone biopsy is required for microarchitecture assessment, and accessible non-invasive techniques are needed. In this study, we tested the short-term reproducibility and parameter changes of a non-invasive method for microarchitecture assessment with a medical computed tomography. Texture parameters (run lengths and co-occurrence) were extracted from bone sample images. Reproducibility and the influence of slice thickness (1, 3, 5 and 8mm) were also studied. After five repositionings, short-term reproducibility was found to be good. All run length parameters but one fell significantly with increasing slice thickness. Co-occurrence parameters showed different patterns of change. Short-term coefficients of variation of texture parameters used to assess bone microarchitecture were similar to those obtained elsewhere with other techniques. The results were influenced by slice thicknesses, emphasizing the importance of the conditions of acquisition. PMID- 17869470 TI - Contrast-enhanced sonography in pancreatic diseases. AB - Contrast-enhanced sonography is a widely available imaging modality for the diagnosis of pancreatic diseases. With this procedure, pancreatic tumours can be differentiated better. Furthermore, contrast-enhanced sonography produces good results in the staging of acute pancreatitis severity, especially in the detection of pancreatic necrosis. In this review article the value of contrast enhanced sonography in the diagnosis of pancreatic diseases will be described and discussed. PMID- 17869471 TI - The role of 3D-CTA in the assessment of peripheral vascular lesions in trauma patients. AB - PURPOSE: The goal of any imaging in the setting of a level 1 trauma center is to assess the injuries of a patient as fast as possible with the least amount of time spend to move the patients between rooms or scanners in order to reduce the time till final diagnosis. CT-angiography (CTA) has become increasingly used to analyze peripheral vascular lesions in blunt and penetrating trauma. METHODS: Diagnostic angiography and CTA are competing methods for the display of peripheral vascular lesions. The specific advantages and shortcomings of both techniques for the routine use in a trauma center are discussed. RESULTS: The inherent limitations of the spatial and temporal resolution of a CTA are compensated by the availability of the procedure and reduced time needed for the final diagnosis. CONCLUSION: 3D-CTA with multislice CT (MSCT) can be used to replace the diagnostic angiography in patients with blunt or penetrating extremity injuries. PMID- 17869472 TI - Simultaneous quantitative analysis of oxcarbazepine and 10,11-dihydro-10 hydroxycarbamazepine in human plasma by liquid chromatography-electrospray tandem mass spectrometry. AB - A fast and sensitive method to quantify oxcarbazepine (OXC) and its active metabolite, 10,11-dihydro-10-hydroxycarbamazepine (MHD) in human plasma using HPLC-MS/MS has been developed. The method involved liquid-liquid extraction (LLE), with diethyl ether-diclhoromethane (60:40v/v) using deuterade carbamazepine (d10-carbamazepine) as internal standard (IS). The analytes and IS were separated using an isocratic mobile phase (acetonitrile/water (50:50v/v)+20 mM acetic acid) on the analytical column Phenomenex Luna C18 5 microm (150 mm x 4.6 mm) at room temperature. Detection was performed by a Micromass Quatro LC mass spectrometer in the reaction monitoring mode using positive electrospray ionization (ESI+). The MS-MS ion transition monitored were m/z 253>208 for OXC, m/z 255>194 for MHD and m/z 247>204 for IS. Over the range 20-5250 ng/ml for OXC and 40-10,500 ng/ml for MHD, the calibration curves were defined by the following equations: y = 0.00568 + 0.00296x -5.70e - 8x(2) and y = 0.00749 + 0.00178x - 5.70e - 8x(2) for OXC and MHD, respectively. All coefficient of determination (r(2)) were close to unity (0.9986-0.9994). The lower limits of quantification obtained as a result of the LLE procedure was 20 ng/ml for OXC and 40 ng/ml for MHD. The statistical evaluation of the developed method was conducted by examining within-batch and between-batch precision data, which were within the required limits. The suitability of the assay for pharmacokinetics studies was determined by measuring OXC and MHD concentration after administration of a single 10 ml of OXC oral suspension (6%) in plasma human of healthy volunteers. PMID- 17869473 TI - Real-time therapeutic drug monitoring of cefozopran in plasma using high performance liquid chromatography with ultraviolet detection. AB - A simple, rapid, and precise HPLC method using ultrafiltration to remove plasma protein was developed to determine cefozopran concentrations in human plasma for real-time therapeutic drug monitoring. Plasma was separated by centrifugation at 4 degrees C from blood collected in heparinized vacuum tubes. Cefozopran and an internal standard were detected by ultraviolet absorbances at 235 nm with no interfering plasma peak. The calibration curve of cefozopran in human plasma was linear from 0.2 to 200 microg/ml. The limit of detection was 0.05 microg/ml. The assay was applied to febrile neutropenia patients in a clinical setting. PMID- 17869474 TI - Differential maturation of chloride homeostasis in primary afferent neurons of the somatosensory system. AB - Recent research into the generation of hyperalgesia has revealed that both the excitability of peripheral nociceptors and the transmission of their afferent signals in the spinal cord are subject to modulation by Cl(-) currents. The underlying Cl(-) homeostasis of nociceptive neurons, in particular its postnatal maturation, is, however, poorly understood. Here we measure the intracellular Cl( ) concentration, [Cl(-)]i, of somatosensory neurons in intact dorsal root ganglia of mice. Using two-photon fluorescence-lifetime imaging microscopy, we determined [Cl(-)]i in newborn and adult animals. We found that the somatosensory neurons undergo a transition of Cl(-) homeostasis during the first three postnatal weeks that leads to a decline of [Cl(-)]i in most neurons. Immunohistochemistry showed that a major fraction of neurons in the dorsal root ganglia express the cation chloride co-transporters NKCC1 and KCC2, indicating that the molecular equipment for Cl(-) accumulation and extrusion is present. RT-PCR analysis showed that the transcription pattern of electroneutral Cl(-) co-transporters does not change during the maturation process. These findings demonstrate that dorsal root ganglion neurons undergo a developmental transition of chloride homeostasis during the first three postnatal weeks. This process parallels the developmental "chloride switch" in the central nervous system. However, while most CNS neurons achieve homogeneously low [Cl(-)]i levels - which is the basis of GABAergic and glycinergic inhibition - somatosensory neurons maintain a heterogeneous pattern of [Cl(-)]i values. This suggests that Cl(-) currents are excitatory in some somatosensory neurons, but inhibitory in others. Our results are consistent with the hypothesis that Cl(-) homeostasis in somatosensory neurons is regulated through posttranslational modification of cation-chloride co-transporters. PMID- 17869475 TI - An algorithm for choosing among smoking cessation treatments. AB - Currently, there are nine validated medications, four validated psychosocial strategies, and three validated ways to deliver psychosocial treatments for smoking cessation. This article presents an algorithm based on a literature review and the author's clinical experience. The algorithm integrates the recommendations of the major guidelines and meta-analyses and provides rationales for its treatment decisions. The algorithm suggests a brief assessment followed by use of one to two medications and counseling in most smokers. Because all treatments appear equally effective and have few adverse events, the algorithm suggests clinicians inform smokers of the pros and cons of the different treatments, and recommend use of one or more of each. If a smoker fails to quit, the algorithm suggests an assessment of why relapse occurred and then a more intense treatment, a new treatment, or both. PMID- 17869476 TI - Hepatitis B vaccination: an unmet challenge in the era of harm reduction programs. AB - The prevalence of vaccination against hepatitis B virus (HBV), factors associated with vaccination, and missed opportunities for vaccination were assessed among 949 street-recruited young injecting heroin users (IHUs) and noninjecting HUs (NIHUs). A cross-sectional study was carried out in Madrid, Barcelona, and Seville. Face-to-face interviews were held using a structured questionnaire with computer-assisted personal interviewing. Dried blood spot samples were tested for anti-HBV core antigen and HBV surface antigen. Bivariate and logistic regression analyses were performed. The prevalence of HBV vaccination was 21.7%, with significant differences among the cities (13.3% in Madrid, 18.4% in Seville, and 33.2% in Barcelona) and between IHUs (23.8%) and NIHUs (17.9%). In the logistic regression analysis, living in Barcelona and being aged 25 years or younger were associated with HBV vaccination in IHUs and NIHUs; in IHUs, vaccination was also associated with living in the street or in institutions for most of the last 12 months. Practically all those susceptible to HBV infection had missed at least one opportunity for vaccination, and most of them had missed such an opportunity in the last year. The proportion of vaccinated HUs remains very low despite efforts to set up harm reduction programs. New and more active strategies must be incorporated in these programs. PMID- 17869477 TI - P518/Qrfp sequence polymorphisms in SAMP6 osteopenic mouse. AB - Mice lacking GPR103A expression display osteopenia. Analysis of mouse quantitative trait loci literature associated with bone mineral density suggested GPR103A ligand P518/Qrfp (chromosome 2qB) as a candidate osteoporosis gene. Promoter and coding regions of mouse P518/Qrfp were sequenced from genomic DNA obtained from the osteoporosis-prone strain SAMP6 and control strains SAMR1, A/J, AKR/J, BALB/c, C3H/HeJ, C57BL/6J, and DBA/2J. Four single-nucleotide polymorphisms (SNPs) were identified in only SAMP6 genomic DNA, g.-1773 T-->C, g.110 A-->G (N37S), g.188 G-->A (R63K), and g.135 T-->C (H45H). The promoter SNP generated a novel neuron-restrictive silencing factor binding site, a repressor that decreases gene expression in nonneuronal tissues. TaqMan analysis demonstrated fivefold lower P518/Qrfp liver expression in SAMP6 versus SAMR1 or C57BL/6J control strains. Tissue distribution of human, mouse, and rat P518/Qrfp and its receptors showed expression in bone and spinal cord. A direct role for P518/Qrfp function in maintaining bone mineral density is suggested. PMID- 17869478 TI - IL-1 beta signaling is required for mechanical allodynia induced by nerve injury and for the ensuing reduction in spinal cord neuronal GRK2. AB - Many neurotransmitters involved in pain perception transmit signals via G protein coupled receptors (GPCRs). GPCR kinase 2 (GRK2) regulates agonist-induced desensitization and signaling of multiple GPCRs and interacts with downstream molecules with consequences for signaling. In general, low GRK2 levels are associated with increased responses to agonist stimulation of GPCRs. Recently, we reported that in mice with reduced GRK2 levels, inflammation-induced mechanical allodynia was increased. In addition, mice with impaired interleukin (IL)-1 beta signaling did not develop mechanical allodynia after L5 spinal nerve transection (SNT). We hypothesized that in the L5 SNT model mechanical allodynia would be associated with reduced neuronal GRK2 levels in the spinal cord dorsal horn and that IL-1 beta signaling would be required to induce both the decrease in GRK2 and mechanical allodynia. We show here that in wild type (WT) mice L5 SNT induces a bilateral decrease in neuronal GRK2 expression in the lumbar spinal cord dorsal horn, 1 and 2 weeks after L5 SNT. No changes in GRK2 were observed in the thoracic segments. Moreover, spinal cord GRK2 expression was not decreased in IL 1R(-/-) mice after L5 SNT. These data show that IL-1 beta signaling is not only required for the development of mechanical allodynia, but also to reduce neuronal GRK2 expression. These results suggest a functional relation between the L5 SNT induced IL-1 beta-mediated decrease in GRK2 and development of mechanical allodynia. PMID- 17869479 TI - Antioxidant status in the serum of persons with intellectual disability and hypothyroidism: a pilot study. AB - Hypothyroidism (HPO) in humans is widely believed to impair health. The biochemical factors mediating decline in health, however, are poorly elucidated. Pathological consequences of HPO point to a high potential for antioxidant imbalance. The objectives of this study were to investigate the major antioxidants in persons with intellectual disability (ID) and HPO in order to find the effect of chronic disease on the level of antioxidative parameters. This is a prospective, nonrandomized study. A total of 11 people with HPO and 11 age matched healthy participants were examined. The following antioxidative defense were examined: superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH Px), and glutathione reductase (GR) as well as two biochemical parameters creatinine and albumin. Compared to healthy control subjects without complications, persons with ID and HOP had significantly lower SOD (p<0.05), catalase (p<0.05), GSH-Px (p<0.05), except the GR level (p=NS). A significant correlation was found between age and gender and AO values in experimental group SOD (r=-0.882), catalase (r=-0.724) and GSH-Px (r=-0.782). Our preliminary results confirm the hypothesis that there is a reduction of the antioxidative defense in persons with HPO and in particularly among males. PMID- 17869480 TI - Decreased sensitivity in adolescent vs. adult rats to the locomotor activating effects of toluene. AB - Volatile organic solvent (inhalant) abuse continues to be a major health concern throughout the world. Of particular concern is the abuse of inhalants by adolescents because of its toxicity and link to illicit drug use. Toluene, which is found in many products such as glues and household cleaners, is among the most commonly abused organic solvents. While studies have assessed outcomes of exposure to inhalants in adult male animals, there is little research on the neurobehavioral effects of inhalants in female or younger animals. In attempt to address these shortcomings, we exposed male and female Long-Evans rats to 20 min of 0, 2000, 4000, or 8000 parts per million (ppm) inhaled toluene for 10 days in rats aged postnatal (PN) day 28-39 (adolescent), PN44-PN55, or >PN70 (adult). Animals were observed individually in 29-l transparent glass cylindrical jars equipped with standard photocells that were used to measure locomotor activity. Toluene significantly increased activity as compared to air exposure in all groups of male and female rats with the magnitude of locomotor stimulation produced by 4000 ppm toluene being significantly greater for female adults than during any age of adolescence. The results demonstrate that exposure to abuse patterns of high concentrations of toluene through inhalation can alter spontaneous locomotor behavior in rats and that the expression of these effects appears to depend upon the postnatal age of testing and sex of the animal. PMID- 17869481 TI - A non-canonical Grb2-PLC-gamma1-Sos cascade triggered by lipovitellin 1, an apolipoprotein B homologue. AB - The injection of the Grb2 adapter in Xenopus oocytes promotes G2/M transition without stimulation from a receptor only the first day after the oocytes removal from the ovaries. This cell cycle reinitiation is Ras-dependent and requires the SH2 and SH3 domains of Grb2. The SH2 domain of Grb2 binds the tyrosine phosphorylated lipovitellin1, a homologue of the human apolipoprotein B. The N SH3 domain of Grb2 is linked to a proline-rich sequence of the C2 domain of PLC gamma1, PLC-gamma1 itself is linked, through its SH3 domain, to the C-terminal proline-rich region of Sos. When Grb2-PLC-gamma1-Sos is associated, PLC-gamma1 is not phosphorylated on Y783 but shows a phospholipase activity. Inhibition of lipovitellin 1 or PLC-gamma1 avoids Grb2-induced cell cycle reinitiation. Therefore, the Grb2-lipovitellin 1 association is the starting point of a novel signaling pathway, where PLC-gamma1 binds Grb2 and recruits Sos. PMID- 17869482 TI - Relationship between stress, eating behavior, and obesity. AB - Stress is thought to influence human eating behavior and has been examined in animal and human studies. Our understanding of the stress-eating relation is confounded by limitations inherent in the study designs; however, we can make some tentative conclusions that support the notion that stress can influence eating patterns in humans. Stress appears to alter overall food intake in two ways, resulting in under- or overeating, which may be influenced by stressor severity. Chronic life stress seems to be associated with a greater preference for energy- and nutrient-dense foods, namely those that are high in sugar and fat. Evidence from longitudinal studies suggests that chronic life stress may be causally linked to weight gain, with a greater effect seen in men. Stress-induced eating may be one factor contributing to the development of obesity. Future studies that measure biological markers of stress will assist our understanding of the physiologic mechanism underlying the stress-eating relation and how stress might be linked to neurotransmitters and hormones that control appetite. PMID- 17869483 TI - Ideal weight better predicts resting energy expenditure than does actual weight in patients with short bowel syndrome. AB - OBJECTIVE: The objective of the present study was to compare measured energy expenditure with predicted energy expenditure in patients with short bowel syndrome. METHODS: Thirteen patients with short bowel syndrome underwent anthropometric measurements and indirect calorimetry for the determination of resting energy expenditure. Energy expenditure was also estimated by use of the Harris-Benedict equation with current weight and ideal weights. RESULTS: The difference between measured energy expenditure and energy expenditure estimated by use of current weight was statistically significant, whereas the difference between measured energy expenditure and energy expenditure estimated by use of ideal weight was not significant. CONCLUSION: The energy expenditure of patients with short bowel syndrome can be estimated by use of the Harris-Benedict equation and patients' ideal weight. PMID- 17869484 TI - Effects of CLA at different dietary fat levels on the nutritional status of rats during protein repletion. AB - OBJECTIVE: Protein depletion is associated with decreased body weight gain, low nitrogen balance, intrahepatic lipid accumulation, and hypoalbuminemia. Because conjugated linoleic acid (CLA) can increase lean body mass, enhance feed efficiency, and modulate lipid metabolism, this study investigated the effects of CLA at two levels of dietary fat on energy efficiency, nitrogen retention, and plasmatic and hepatic lipid levels in rats during dietary protein repletion. METHODS: The animals were subjected to a moderate protein restriction for 14 d. After that, they were fed a protein repletion diet for 30 d, supplemented or not with CLA at recommended and high-fat levels. Energy efficiency, nitrogen balance, and nutritional parameters in serum and tissues were evaluated. RESULTS: Protein repletion improved most of the nutritional parameters evaluated independently of CLA supplementation at both fat levels. At recommended fat levels, CLA did not have any effect. At high-fat levels, energy efficiency increased more than 20% by fat accumulation in carcasses and epididymal pads, serum cholesterol increased (two-fold), and liver triacylglycerol accumulation remained elevated. However, at high-fat levels, CLA prevented lipid accumulation in liver and adipose tissue. CONCLUSION: Protein repletion improved the nutritional status of protein restricted rats with minor effects of CLA at both dietary fat levels. However, when high-fat diets were given, CLA-enriched oil showed preventive effects on liver and adipose tissue lipid accumulation and no deleterious effects were observed. Because there are no studies dealing with CLA effects on protein repletion, this experimental model could improve nutritional interventions to overcome the protein-deficit stage. PMID- 17869487 TI - Overexpression of phosphorylated ATF2 and STAT3 in eccrine porocarcinoma and eccrine poroma. PMID- 17869486 TI - Brain-derived neurotrophic factor polymorphisms and smoking in schizophrenia. PMID- 17869488 TI - Sensitive voltammetric determination of tyrosine using multi-walled carbon nanotubes/4-aminobenzeresulfonic acid film-coated glassy carbon electrode. AB - A chemically modified electrode is constructed based on the multi-walled carbon nanotubes (MWNTs)/4-aminobenzeresulfonic acid (4-ABSA) film-coated glassy carbon electrode. The electrocatalytic oxidation of tyrosine (Tyr) is investigated on the surface of the MWNTs/4-ABSA-modified electrode using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The prepared modified electrode shows voltammetric responses with high sensitivity and selectivity for Tyr in optimal conditions, which makes it very suitable for sub-micromolar detection of Tyr. A sensitive oxidation peak at +0.64 V is employed to determine Tyr. Good linear relationship between the oxidation peak current and the Tyr concentration in the range of 1x10(-7) to 5x10(-5) mol/L is obtained in phosphate buffer solution with pH 7.0. By use of modified electrode, the voltammetric detection limit for Tyr in DPV measurements is 8x10(-8) mol/L (S/N=3). Good sensitivity, selectivity and stability of the low-cost modified electrode make it very suitable for the determination of trace amounts of Tyr in pharmaceutical and clinical preparations. PMID- 17869489 TI - Self-aggregated nanoparticles from methoxy poly(ethylene glycol)-modified chitosan: synthesis; characterization; aggregation and methotrexate release in vitro. AB - Methoxy poly(ethylene glycol)-grafted-chitosan (mPEG-g-CS) conjugates were synthesized by formaldehyde linking method and characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance ((1)H-NMR). The degree of substitution (DS) of methoxy poly (ethylene glycol) (mPEG) in the mPEG-g-CS molecules determined by (1)H-NMR ranged from 19% to 42%. The critical aggregation concentration (CAC) was determined by fluorescence spectroscopy using pyrene as fluorescence probe and its value was 0.07 mg/mL in water. mPEG-g-CS formed monodisperse self-aggregated nanoparticles with a roughly spherical shape and a mean diameter of 261.9 nm were prepared by the dialysis method. mPEG-g-CS self aggregated nanoparticles were used as carriers of poorly water-soluble anticancer drug methotrexate (MTX). MTX was physically entrapped inside mPEG-g-CS self aggregated nanoparticles by dialysis method and the characteristics of MTX-loaded mPEG-g-CS self-aggregated nanoparticles were analyzed using dynamic laser light scattering (DLLS), transmission electron microscopy (TEM). Moreover, in vitro release behavior of MTX was also investigated and the results showed that MTX was continuously released more than 50% in 48 h. PMID- 17869490 TI - Immobilization of heavy metals by Pseudomonas putida CZ1/goethite composites from solution. AB - Bacterial-mineral composites are important in the retention of heavy metals due to their large sorption capacity under a wide range of environmental conditions. This study provides the first quantitative comparison of the metal-binding capacities of P. putida CZ1-goethite composite to its individual components. When the same amount (on a dry weight basis) of living and nonliving cells of P. putida CZ1, goethite or their composites was separately exposed to solutions of 0.5 mM Cu(II) and Zn(II) in 0.01 M KNO(3), the living cells removed the largest quantity of heavy metals. The results of calculated metal retention values indicated that the adsorption of goethite to bacteria has not mask or neutralize chemically reactive adsorption sites normally available to metal ions. Moreover, the nonliving cells-goethite composite retained approximately 82% more Zn than that predicted by their individual behavior. The preferential association of Zn with P. putida CZ1 was observed by TEM and EDS analyses of a mixture consisting of the bacteria and goethite. Desorption of Cu and Zn with 1.0M CH(3)COOK solution from P. putida CZ1 and goethite indicated the differences in the functional groups able to bind heavy metals. PMID- 17869491 TI - Clonidine accumulation in human neuronal cells. AB - After transport across several epithelial barriers including the blood-brain barrier, clonidine interacts with alpha(2)-adrenergic receptors and imidazoline binding sites in the brain. We hypothesized that neuronal cells take up clonidine thereby removing the drug from the extracellular fluid compartment. Uptake of [(3)H]clonidine into SH-SY5Y neuroblastoma cells was linear for up to 1 min, unaffected by inside directed Na(+) or Cl(-) gradients but strongly inhibited by an outside pH of 6.0. The cells accumulated [(3)H]clonidine 50-70-fold uphill against a concentration gradient. Unlabeled clonidine, guanabenz, imipramine, diphenhydramine, maprotiline, quinine and the endogenous monoamine phenylethylamine (2 mM) strongly inhibited the [(3)H]clonidine uptake by 60-95%. Tetraethylammonium, choline and N-methyl-4-phenylpyridinium had no effect. The accumulation at pH 7.5 was saturable with an apparent Michaelis-Menten constant (K(t)) of 0.7 mM. We conclude that SH-SY5Y cells not only bind clonidine to extracellular receptors but also take up the drug rapidly by a specific and concentrative mechanism. PMID- 17869492 TI - Is there a limit to dose escalation for rectal cancer? AB - The radiation tolerance of the rectum is not fully understood. Published studies on the radiation treatment of cancers of the prostate, cervix and rectum have been reviewed to determine currently recommended dose-volume guidelines. The need for further studies directed specifically at the treatment of primary rectal cancer and perirectal node metastases is discussed. There seems to be room for escalation of the external beam doses currently given. PMID- 17869493 TI - Radiotherapy for early rectal cancer. PMID- 17869494 TI - Dimethoate-induced biochemical and histopathological changes in the liver of rats. AB - Dimethoate is an organophosphorus insecticide and acaricide used for the control of a wide range of insects, including houseflies and mites, on a variety of fruits, vegetables, field and forestry crops. The aim of the current study was to evaluate the subchronic toxicity of orally administered dimethoate in Wistar albino rats, based on the histopathological and biochemical findings in the liver. The animals of the exposed groups were fed with laboratory chow combined with 2, 8 or 20 mg/kg body weight/day dimethoate for 90 consecutive days under controlled laboratory conditions. At the end of the experiment, body weight gain, absolute and relative liver weights, liver cholinesterase activities and total protein levels were determined. Histopathological changes in the liver were also determined using a light microscope. Results showed that there were decreases in relative liver weights of exposed rats. Although liver total protein levels were significantly increased, liver cholinesterase activities were decreased in all exposed groups. Dimethoate caused dose-related histopathological changes such as mononuclear cell infiltration, congestion, an enlargement of the veins and sinusoids, hepatocellular damage, necrotic changes, an increase in the number of Kupffer cells, cytoplasmic vacuolization and degeneration in nuclei in the liver of exposed rats. These effects did not vary between the sexes. PMID- 17869495 TI - Spontaneous neoplasms observed in cynomolgus monkeys (Macaca fascicularis) during a 15-year period. AB - A total of 33 tumors were observed during a time period of 15 years (1992-2006) in cynomolgus monkeys. The great majority of neoplasms was benign (23 benign neoplasms versus 10 malignant tumors). Fourteen appeared in males and 19 in females. The age of tumor-bearing animals ranged between 2 years 2 months and 13 years 9 months. Most of the tumors (22) in the cynomolgus monkeys were seen in endocrine organs (adrenal cortical adenoma, adrenal hemangioma, C-cell carcinoma, follicular adenoma), respiratory system (nasal cavity adenoma, pulmonary squamous cell carcinoma, bronchio-alveolar carcinoma, bronchiolar papilloma, chondromatous hamartoma) and female genital system (uterine polyp, uterine adenoma, uterine leiomyoma and teratoma of the ovary). Four animals revealed malignant lymphoma infiltrating multiple organs. PMID- 17869498 TI - Chemical characterization of landfill leachates--400 parameters and compounds. AB - A large number of hazardous compounds can be expected to be present in landfill leachates, many of which have not yet been identified. Thus this study screened samples from 12 Swedish municipal landfill sites for 400 parameters and compounds. More than 90 organic and metal organic compounds and 50 inorganic elements were detected, some of which seem to have not been detected before. Compounds detected include halogenated aliphatic compounds, benzene and alkylated benzenes, phenol and alkylated phenols, ethoxylates, polycyclic aromatic compounds, phthalic esters, chlorinated benzenes, chlorinated phenols, PCB, chlorinated dioxins and chlorinated furans, bromated flame-retardants, pesticides, organic tin, methyl mercury and heavy metals. The presence of this large number of hazardous compounds in landfill leachates should have a significant impact on future landfill risk assessments and the development of leachate treatment methods. We propose that future research should pay more attention to the metal-organic and organic compounds detected in this study. We also suggest using leachate sediments as a matrix for detecting hydrophobic compounds, and reflecting on the degradation phase when evaluating results from monitoring studies. The extensive compilation of compounds in this paper can be used to select compounds to search for in future studies. PMID- 17869497 TI - Early administration of two intravenous bolus of aminophylline added to the standard treatment of children with acute asthma. AB - OBJECTIVES: Evaluate the efficacy of adding two intravenous bolus of aminophylline to the standard treatment of acute asthma episode in children admitted to the pediatric emergency room (PER). METHODS: Between March 2001 and February 2002, 60 children (2-5 years old), admitted to the PER at Hospital de Clinicas de Porto Alegre (Brazil), due to an episode of acute asthma, refractory to conventional therapy (an oral dose of steroids and at least three doses of inhaled albuterol, associated or not with oxygen) were enrolled in a randomized, double blind, placebo controlled clinical trial. The randomization was performed in blocks of 10 patients, who received a "bronchodilator solution" (either saline or aminophylline), in two doses: on arrival at the PER and again 6h later. The intervention group received aminophylline 5mg/kg/dose diluted in normal saline (NS) solution up to a 20 mL volume, while the placebo group received plain NS, both in an infusion rate of 1 cc/min. The main outcomes were total length of hospital stay, length of supplemental oxygen use, number of bronchodilator nebulizations and/or aerosol inhalations performed and patient destination. The groups were compared using the Students t-test, Mann-Whitney test and Chi-Square test, accepting p<0.05 as significant. RESULTS: Comparing the main outcomes, we did not find differences between the placebo and aminophylline groups: 29.0+/ 14.7 versus 26.2+/-13.4 beta-agonist nebulizations per patient (p=0.46); 2.4+/ 10.6 versus 5.6+/-14.2 aerosol inhalations per patient (p=0.32); 24.7+/-30.0 versus 26.0+/-25.2h for oxygen supplement (p=0.86); 43.2+/-30.0 versus 43.6+/ 23.7h for length of hospital stay (p=0.95). We also did not find differences between the two groups related to the blood pressure, heart rate, respiratory rate and oxygen saturation. CONCLUSION: In children aged 2-5 years admitted to a PER with asthma, two intravenous doses of 5mg/kg of aminophylline given 6h apart did not change the length of stay in hospital, the number of nebulizations given or the duration of oxygen therapy required. We are unable to tell whether there would be benefit with higher doses of aminophylline designed to give levels in the usual therapeutic range. PMID- 17869499 TI - Analysis of land suitability for the siting of inter-municipal landfills in the Cuitzeo Lake Basin, Mexico. AB - This paper presents three spatial decision-support models (Boolean logic, binary evidence and overlapping index of multiple class maps) to perform a land suitability analysis for sanitary landfill siting. The study was carried out in the basin of Lake Cuitzeo, Mexico, with the objective of locating areas that comply with environmental regulations and with the inter-municipality criterion, i.e., that are accessible by at least two municipalities. Biophysical and socio economic data were processed in a Geographic Information System (GIS). The three models differ in their complexity and restrictiveness. The Boolean logic model is easier to apply and more restrictive than the other two, because it is based on the assessment of single attributes. On the other hand, the binary data and overlapping index methods are relatively more complex because they require attribute weighting. The results showed that 23 of the 28 municipalities included in the basin have at least one area that was classified as highly suitable. The most suitable areas covered from 63.8 to 204.5 km(2) (from 1.5% to 5%), and they are not distributed homogeneously, but clustered around four main sites. The larger and most suitable of these sites is located in the central part of the basin, and it can be accessed by five of the most densely populated municipalities. The proposed approach represents a low-cost alternative to support a common spatial decision-making process in developing countries. PMID- 17869500 TI - Investigating solid waste production and associated management practices in private dental units. AB - In the municipality of Thessaloniki in 2006 mercury-bearing dental wastes were not managed properly by 80% of dentists and metal-bearing waste was handled in accordance with internationally established best management practices by less than 50% of dentists. Those results were documented through a biennial field based research study that took place in private dental units within the Thessaloniki Urban Area. For quantifying the waste produced, structured questionnaires were used and interviews with dentists were performed. In the present work, results of this survey are presented; critical parameters and factors affecting the quantity and quality of the dental waste stream are reported together with the analysis and classification of dominant conditions and needs of the dental sector in the waste management field. PMID- 17869501 TI - Detecting penicillin G in milk with impedimetric label-free immunosensor. AB - A label-free impedimetric flow injection immunosensor for the direct detection of penicillin G has been developed. Anti-penicillin G was immobilized on a gold working electrode modified with a self-assembled monolayer of thioctic acid. Real time monitoring of impedance was carried out at the optimum frequency of 160 Hz. Under optimum operating conditions the system provided a wide linear range between 1.0 x 10(-13) and 1.0 x 10(-8) M with a very low detection limit of 3.0 x 10(-15) M, much lower than the MRL of penicillin G in milk (1.2 x 10(-8) M). The immobilized anti-penicillin G on self-assembled thioctic acid monolayer gold electrode was very stable and provided good reproducible signal after regeneration up to 45 times with a relative standard deviation (R.S.D.) lower than 4%. Good recoveries and precisions were obtained when spiked raw milk samples were analyzed. PMID- 17869502 TI - Lab-on-a-chip immunoassay for multiple antibodies using microsphere light scattering and quantum dot emission. AB - Double detection of microsphere light scattering and quantum dot emission was demonstrated for lab-on-a-chip immunoassay without using stationary support. We conjugated quantum dots (QDs) onto microspheres to enable multiplex assays as well as to enhance the limit of detection (LOD). We named this configuration "nano-on-micro" or "NOM". Upon radiation with UV light (380nm), a stronger light scattering signal is observed with NOMs than QDs or microspheres alone. Additionally, NOMs are easier to handle than QDs. Since QDs also provide fluorescent emission, we are able to utilize an increase in light scattering for detecting antigen-antibody reaction and a decrease in QD emission to identify which antibody (or antigen) is present. Two types of NOM combinations were used. One batch of microspheres was coated with QDs emitting at 655 nm and mouse IgG (mIgG); the other with QDs emitting at 605 nm and bovine serum albumin (BSA). A mixture of these two NOMs was used to identify either anti-mIgG or anti-BSA. NOM particles and target solutions were mixed in a microfluidic device (using highly carboxylated microspheres as previously demonstrated by our group) and on-chip detection was performed using proximity optical fibers. Forward light scattering at 380 nm was collected. With the positive target, the scattering signal was increased. The LOD was as low as 50 ng ml(-1) (330 pM) with p<0.05. Fluorescent emission (655 or 605 nm) was simultaneously collected. With the positive target, the emission signal was attenuated. Therefore, we were able to detect two different antibodies simultaneously with two different detection protocols. We believe this NOM bioassay has the ability to screen for and detect multiple antibodies with minimal sample processing and handling (one-step lab-on-a-chip immunoassay). PMID- 17869503 TI - Moss bioreactors producing improved biopharmaceuticals. AB - Plants may serve as superior production systems for complex recombinant pharmaceuticals. Current strategies for improving plant-based systems include the development of large-scale production facilities as well as the optimisation of protein modifications. While post-translational modifications of plant proteins generally resemble those of mammalian proteins, certain plant-specific protein linked sugars are immunogenic in humans, a fact that restricts the use of plants in biopharmaceutical production so far. The moss Physcomitrella patens was developed as a contained tissue culture system for recombinant protein production in photo-bioreactors. By targeted gene replacements, moss strains were created with non-immunogenic humanised glycan patterns. These were proven to be superior to currently used mammalian cell lines in producing antibodies with enhanced effectiveness. PMID- 17869504 TI - X inactivation Xplained. AB - Random inactivation of one of the two female X chromosomes establishes dosage compensation between XY males and XX females in placental mammals. X inactivation is controlled by the X inactivation center (Xic). Recent advances in genome sequencing show that the Xic has evolved from an ancestral vertebrate gene cluster in placental mammals and has undergone separate rearrangements in marsupials. The Xic ensures that all but one X chromosome per diploid genome are inactivated. Which chromosome remains active is randomly chosen. Pairing of Xic loci on the two X chromosomes and alternate states of the X chromosomes before inactivation have recently been implicated in the mechanism of random choice. Chromosome-wide silencing is then initiated by the noncoding Xist RNA, which evolved with the mammalian Xic and covers the inactive X chromosome. PMID- 17869505 TI - Steady state model for evaluation of external and internal mass transfer effects in an immobilized biofilm. AB - A steady model for the evaluation of external liquid film diffusion and internal pore diffusion effects in an immobilized biofilm system under continuous mode of operation was developed. The model takes into account, substrate diffusion through external liquid film and biofilm. Average rate of substrate consumption in the biofilm was considered. The overall efficiency of the biofilm was mathematically represented by considering the combined effects of substrate penetration and substrate utilization in the biofilm. The model was illustrated using a case study of pyridine biodegradation in a rotating biological contactor immobilized with pyridine degrading microbial film. The model is able to effectively predict both internal and external mass transfer effects in an immobilized biofilm system. PMID- 17869506 TI - Pullulan-hyperproducing color variant strain of Aureobasidium pullulans FB-1 newly isolated from phylloplane of Ficus sp. AB - The studies were carried out for the isolation of efficient pullulan producing strains of Aureobasidium pullulans. Five strains were isolated from phylloplane of different plants. Amongst these, three were producing black pigment melanin, while the remaining two produced pink pigment. These two color variant isolates of A. pullulans were designated as FB-1 and FG-1, and obtained from phylloplane of Ficus benjamina and Ficus glometa, respectively. The parameters employed for the identification of the isolates included morphology, nutritional assimilation patterns and exopolysaccharide (EPS) production. Isolates were compared with standard cultures for EPS production. A. pullulans FB-1 was the best producer of pullulan giving up to 1.9, 1.4 and 1.7 times more pullulan than the control of A. pullulans NCIM 976, NCIM 1048 and NCIM 1049, respectively. The IR spectra of the isolates and standard strains revealed that the polysaccharide was pullulan, but not aubasidan. The study also supported the fact that A. pullulans is a ubiquitous organism and phylloplane being the important niche of the organism. PMID- 17869507 TI - New biologically active epidioxysterols from Stereum hirsutum. AB - From the fungus Stereum hirsutum have been isolated and identified two new epidioxysterols 1, 4, together with two known ones 2 and 3. Their structures were elucidated on the basis of spectroscopic analysis and chemical reactions. Epidioxysterols 1-4 have been shown to possess a significant activity against Mycobacterium tuberculosis. PMID- 17869508 TI - Design and synthesis via click chemistry of 8,9-anhydroerythromycin A 6,9 hemiketal analogues with anti-MRSA and -VRE activity. AB - An erythromycin analogue, 11,12-di-O-iso-butyryl-8,9-anhydroerythromycin A 6,9 hemiketal (1b), was found to be a potential anti-MRSA and anti-VRE agent. The use of copper catalyzed azide-acetylene cycloaddition, and click chemistry, readily provided 10 types of triazole analogues of 1b in good to nearly quantitative yield. Among the library, 5b exhibited activity against MRSA and VRE bacterial strains, representing more than twice the potency of 1b. PMID- 17869509 TI - Amino-caprolactam derivatives as gamma-secretase inhibitors. AB - A series of amino-caprolactam sulfonamides were developed from a screening hit. Compounds with good in vitro and in vivo gamma-secretase activity are reported. PMID- 17869510 TI - Synthesis and inhibitory activity of 4-alkynyl and 4-alkenylquinazolines: identification of new scaffolds for potent EGFR tyrosine kinase inhibitors. AB - The present study identified several 4-alkynyl and 4-alkenylquinazolines that serve as novel and potent EGFR tyrosine kinase inhibitors. The IC(50) values of these compounds are in the nanomolar range. In addition, the 4-(4-phenylbut-1 yn/en-yl)quinazolines provided scaffolds for potent enzyme inhibition. Chiral discrimination was observed to occur in one of the 4-alkynylquinazoline derivatives with the (R)-isomer being more than 150 times as potent as the (S) isomer. PMID- 17869511 TI - Quantitative structure-activity relationship studies for prediction of antimicrobial activity of synthesized 2,4-hexadienoic acid derivatives. AB - A new series of 2,4-hexadienoic acid derivatives (S(1)-S(42)) has been synthesized and evaluated as antimicrobial agents against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans, and Aspergillus niger. Quantitative structure-activity relationship (QSAR) investigation using Hansch analysis was applied to find out correlation between antimicrobial activities with physicochemical properties of the synthesized compounds. Various physicochemical descriptors and experimentally determined minimum inhibitory concentration values for different microorganisms were used as independent and dependent variables, respectively. The QSAR revealed that topological parameters especially molecular connectivity indices (chi(2), (0)chi(v), (2)chi(v)) were found to have overall significant correlation with antimicrobial activity of 2,4 hexadienoic acid derivatives. The statistical results of training set, cross validated r(2) and conventional r values gave reliability to the prediction of molecules with activity using QSAR models. PMID- 17869512 TI - A novel class of potent NF-kappaB signaling inhibitors. AB - A novel class of NF-kappaB pathway signaling inhibitors was discovered by virtual screening, medicinal chemistry, and QSAR analysis. An initial set of compounds inhibited NF-kappaB signaling in a whole cell reporter gene assay in the micro molar range. Activity was improved step by step by medicinal chemistry to yield nano-molar signaling inhibitors. PMID- 17869513 TI - Imidazopiperidine amides as dipeptidyl peptidase IV inhibitors for the treatment of diabetes. AB - A series of substituted imidazopiperidine amides has been prepared and evaluated for inhibition of dipeptidyl peptidase IV (DPP-4). Substitution at the 1- and 3 positions produced increased selectivity for DPP-4 relative to DPP-8 and DPP-9. Compounds in this series had IC(50) values as low as 5.8 nM for inhibition of DPP 4. PMID- 17869514 TI - Neutral 5-substituted 4-anilinoquinazolines as potent, orally active inhibitors of erbB2 receptor tyrosine kinase. AB - Neutral 5-substituted 4-anilinoquinazolines addressed high in vivo clearance and phospholipidosis associated with previous basic compounds. A representative compound 8a inhibited tumor growth in a mouse xenograft model when co administered with the cytochrome P450 inhibitor 1-aminobenzotriazole (ABT), and data are consistent with pharmacology primarily reflecting inhibition of erbB2 receptor tyrosine kinase. PMID- 17869515 TI - Discovery of N-phenyl nicotinamides as potent inhibitors of Kdr. AB - Inhibition of tumor-induced angiogenesis is a promising strategy in anticancer research. Neovascularization is a process required for both tumor growth and metastasis. Enhanced understanding of the underlying molecular mechanisms has led to the discovery of a variety of pharmaceutically attractive targets. Decades of investigation suggest that vascular endothelial growth factor (VEGF) and its receptors, in particular VEGFR2 or kinase insert-domain-containing receptor (Kdr), play a critical role in the growth and survival of endothelial cells in newly forming vasculature. The clinical utility of inhibitors of this receptor tyrosine kinase is currently under intense investigation. Herein we report our efforts in this arena. PMID- 17869516 TI - Reliability and feasibility of the six minute walk test in subjects with myotonic dystrophy. AB - The objective was to describe test-retest reliability and feasibility of the six minute walk test in adult subjects with myotonic dystrophy type 1. Twelve subjects (28-68 years, mean 44) performed three six minute walk tests on two occasions, one week apart. Relative reliability was high (ICC(2.1)=0.99) and absolute reliability values were low (standard error of measurement 12 m, repeatability 33 m). Feasibility was investigated in a sample of 64 subjects (19 70 years, mean 43). Fifty-two subjects were able to perform two tests on the same day. Subjects with severe proximal weakness had difficulties performing repeated tests. A practice trial followed by a second test on the same day can be recommended for most subjects, and the best test should be used for evaluations. In conclusion, even though the study sample was small, the present study indicates that the six minute walk test is reliable and feasible in subjects with myotonic dystrophy type 1. PMID- 17869517 TI - Protein O-mannosyltransferase activities in lymphoblasts from patients with alpha dystroglycanopathies. AB - Defects in O-mannosylation of alpha-dystroglycan cause some forms of congenital muscular dystrophy (CMD), the so-called alpha-dystroglycanopathies. Six genes are responsible for these diseases with overlapping phenotypes. We investigated the usefulness of a biochemical approach for the diagnosis and investigation of the alpha-dystroglycanopathies using immortalized lymphoblasts prepared from genetically diagnosed and undiagnosed CMD patients and from control subjects. We measured the activities of protein O-mannose beta1,2-N acetylglucosaminyltransferase 1 (POMGnT1) and protein O-mannosyltransferase (POMT). Lymphoblasts from patients harbouring known mutations in either POMGNT1 or POMT1 showed a marked decrease in POMGnT1 or POMT activity, respectively, compared to controls. Furthermore, we identified pathogenic mutations in POMGNT1, POMT1 or POMT2 in six previously genetically uncharacterised patients who had very low enzyme activity. In conclusion, the lymphoblast-based enzymatic assay is a sensitive and useful method (i) to select patients harbouring POMGNT1, POMT1 or POMT2 mutations; (ii) to assess the pathogenicity of new or already described mutations. PMID- 17869518 TI - 151st ENMC international workshop: Inflammatory Neuropathy Consortium 13th-15th April 2007, Schiphol, The Netherlands. PMID- 17869519 TI - Use of a novel bone graft substitute in peri-articular bone tumours of the knee. AB - We treated three patients with aneurysmal bone cysts and seven with giant cell tumours who presented with a large osteolytic lesion in peri-articular areas of the knee. The patients age ranged from 8 to 49 years (mean 25 years). The average tumour volume was measured at 39.8 cm(3) (range 18 to 65 cm(3)). The tumour cavities were treated with curettage, phenolisation and application of a composite bone graft substitute containing 35% calcium-sulphate hemihydrate and 65% hydroxyapatite granules. All patients were followed up for 4.0 to 5.2 years (mean 4.5 years). Tumour recurrence was noted in two cases. In the remaining patients consolidation of the lesion was considered complete at a mean of 4.5 months (3-6.5 months). During follow-up no deformities developed and no radiological signs of joint degeneration were noted. All patients regained close to normal function, with a mean Musculoskeletal Tumour Society Rating Score of 95.1%. Due to their good osteoconductive abilities, composite synthetic bone graft substitute combining porous hydroxyapatite with calcium-sulphate appears to be an effective alternative to autologous cancellous bone graft in the treatment of large osteolytic lesions in peri-articular areas around the knee joint. They bear major advantages through ubiquitous availability and the avoidance of morbidity associated with iliac crest harvest. Concerns remain as the radio opaque appearance of the bone graft substitute may potentially delay the detection of tumour recurrence. PMID- 17869520 TI - Mycobacterium fortuitum infection following total knee arthroplasty: a case report and literature review. AB - Although Mycobacterium fortuitum is ubiquitous in our environment, infection of total knee arthroplasties with this organism is uncommon. This particular mycobacterium belongs to a group of organisms known as rapidly growing mycobacteria that distinguishes itself from the more typical Mycobacterium tuberculosis by their lower virulence and lack of human-to-human transmission. Another distinguishing feature is their resistance to almost all traditional anti tuberculous medications and many antibiotics. Because such infections are encountered so infrequently, delays in reaching a microbiological diagnosis are not unusual. This inevitably compromises patient care. At present, there is no universally accepted treatment protocol. Management tends to be individualized, but cure may be possible with a prolonged course of appropriate anti-microbial therapy, removal of the implant, biopsy to confirm eradication of the organism, and finally, reimplantation of a new prosthesis. This paper presents the successful treatment of such an infection. Use of the combination of meropenem and moxifloxacin has not been previously reported in this setting. This case suggests that their in vivo activity is clinically effective against M. fortuitum peri-prosthetic infections when combined with surgical therapy. PMID- 17869521 TI - Rational design, synthesis and evaluation of (6aR( *),11bS( *))-1-(4 fluorophenyl)-4-{7-[4-(4-fluorophenyl)-4-oxobutyl]1,2,3,4,6,6a,7,11b,12,12a(RS) decahydropyrazino[2',1':6,1]pyrido[3,4-b]indol-2-yl}-butan-1-one as a potential neuroleptic agent. AB - In our pursuit to prepare a potent antipsychotic compound, a novel 1,2,3,4,6,6a,7,11b,12,12a-decahydropyrazino[2',1':6,1]pyrido[3,4-b]indole derivative was synthesized which incorporates the butyrophenone substructure twice. This molecule has shown D(1), D(2) and 5-HT(2A) receptor blocking activity where the ratio pK(i) (5-HT(2A)) to pK(i) (D(2)) is 1.42 better than risperidone (1.15). It blocks amphetamine induced hyperactivity/stereotypy and secondary conditioned avoidance responses in rodents at lower doses than those required for the neuroleptic drugs haloperidol and centbutindole (biriperone). PMID- 17869522 TI - Synthesis, biological evaluation and molecular modelling of sulfonohydrazides as selective PI3K p110alpha inhibitors. AB - A series of 2-methyl-5-nitrobenzenesulfonohydrazides were prepared and evaluated as inhibitors of PI3K. An isoquinoline derivative shows good selectivity for the p110alpha isoform over p110beta and p110delta, and also demonstrates good in vitro activity in a cell proliferation assay. Molecular modelling provides a rationalisation for the observed SAR. PMID- 17869523 TI - Elucidation of the RNA target of linezolid by using a linezolid-neomycin B heteroconjugate and genomic SELEX. AB - A covalently modified heteroconjugate between linezolid and neomycin B leads to an enhanced and more specific binding affinity to hairpin RNA targets in comparison to neomycin B itself. This heteroconjugate was used as a lure to select linezolid-specific hairpin RNA from an Escherichia coli genome RNA. The selected RNA obtained after eight cycles not only has typical stem-loop structures but also includes known sequences of the linezolid binding site. The results of RNA footprinting show that the binding site of the heteroconjugate encompasses both stem and loop regions, suggesting that the possible binding site for linezolid is in the terminal loop. In addition, findings from application of a surface plasmon resonance assay clearly demonstrate that linezolid binds to selected hairpin RNA in a highly specific manner with a low millimolar affinity. The results suggest that heteroconjugates might represent a generally useful approach in studies aimed at uncovering loop-specific RNA binding ligands that would be otherwise difficult to identify owing to their weak affinities. PMID- 17869524 TI - The molecular pruning of a phosphoramidate peptidomimetic inhibitor of prostate specific membrane antigen. AB - To identify the pharmacophore of a phosphoramidate peptidomimetic inhibitor of prostate-specific membrane antigen (PSMA), a small analog library was designed and screened for inhibitory potency against PSMA. The design of the lead inhibitor was based upon N-acyl derivatives of endogenous substrate folyl-gamma Glu and incorporates a phosphoramidate group to interact with the PSMA catalytic zinc atoms. The scope of the analog library was designed to test the importance of various functional groups to the inhibitory potency of the lead phosphoramidate. The IC(50) for the lead phosphoramidate inhibitor was 35 nM while the IC(50) values for the analog library presented a range from 0.86 nM to 4.1 microM. Computational docking, utilizing a recently solved X-ray crystal structure of the recombinant protein, along with enzyme inhibition data, was used to propose a pharmacophore model for the PSMA active site. PMID- 17869525 TI - New oxime reactivators connected with CH2O(CH2)nOCH2 linker and their reactivation potency for organophosphorus agents-inhibited acetylcholinesterase. AB - New bis-pyridinium oxime reactivators 6 with CH(2)O(CH(2))(2)OCH(2) and CH(2)O(CH(2))(4)OCH(2) linkers between the two pyridinium rings were designed and synthesized. In the in vitro test of their potency to reactivate AChE inhibited by organophosphorus agents at 5 x 10(-3)M concentration, the reactivation ability of 1,2-dimethoxy-ethylene-bis-N,N'-4-pyridiumaldoxime dichloride (6a) was 63% for housefly (HF) AChE inhibited by diisopropyl fluorophosphates (DFP), 51% for bovine red blood cell (RBC) AChE inhibited by DFP, 67% for HF-AChE inhibited by paraoxon, and 81% for RBC-AChE inhibited by paraoxon. Except in the case of DFP inhibited HF AChE test of 2-PAM, the activities of 6a are much higher than the activities of 2-PAM and HI-6 which are AChE reactivators currently in use. PMID- 17869526 TI - Molecular probe for enzymatic activity with dual output. AB - A novel molecular probe for enzymatic activity with a dual output detection-mode has been developed. The probe effectively detected the presence of the bacterial protease penicillin-G-amidase; a single cleavage by the enzyme initiated the fragmentation of a self immolative dendritic platform to release two reporter units. The signals of the free reporters were detected by two different spectroscopic techniques, fluorescence and UV-vis. This is the first reported molecular probe with two different chromogenic reporter units activated by a specific stimulus. PMID- 17869527 TI - In vivo growth inhibitory and anti-angiogenic effects of synthetic novel dienone cyclopropoxy curcumin analogs on mouse Ehrlich ascites tumor. AB - In the present study, four novel dienone cyclopropoxy curcumin analogs 1a-4a were synthesized by nucleophillic substitution reaction with cyclopropyl bromide. The tumor inhibitory and anti-angiogenic effects of the synthetic compounds were studied on mouse Ehrlich ascites tumor (EAT) in vivo. The compounds 1a-4a increased the life span (% ILS) of EAT bearing mice with corresponding significant reduction in ascites volume and cell number and induced apoptotic bodies in EAT cells. Anti-angiogenic studies of the compounds demonstrated significant reduction of microvessel density (MVD) in the peritoneum wall sections of mice and induced avascular zone in CAM model. Our findings demonstrate that the tumor growth inhibitory effects of synthetic dienone cyclopropoxy curcumin analogs 1a-4a could be mediated by promoting apoptosis and inhibiting tumor angiogenesis. However, the compounds need to be explored further to assess its clinical relevance. PMID- 17869528 TI - Antennal sensilla of the decapitating phorid fly, Pseudacteon tricuspis (Diptera: Phoridae). AB - Pseudacteon tricuspis Borgmeier is a parasitic decapitating phorid fly (Diptera: Phoridae), which has been released in the southern United States in the last decade for biological control of invasive imported fire ants, Solenopsis spp. In a previous study, we demonstrated that P. tricuspis uses fire ant semiochemicals to locate host worker ants. To provide a solid background in support of our research on mechanisms of host location and olfaction in phorid flies, we studied the morphology of the antennal sensilla of both sexes of P. tricuspis using scanning and transmission electron microscopy. Antennae of P. tricuspis show strong sexual dimorphism in structure and shape: the female has a feathered arista which is located distally on the flagellum and has three sub-segments that bear small spinules of microtrichia. The first two antennal segments, scape and pedicel, bear no sensillum, but were densely covered by microtrichia. Three major types of sensilla were found on the flagellum (funicle) of both sexes: sensilla trichodea, sensilla basiconica, and sensilla coeloconica. Two of these, s. trichodea and s. basiconica were differentiated into three (short, medium, and long) and two (blunt-tip and sharp-tip) subtypes, respectively, for a total of six morphologically different sensilla subtypes. Ultrastructural studies revealed multiple wall pores on s. trichodea and s. basiconica, possibly suggesting chemoreceptory functions. The third and least abundant sensilla type, s. coeloconica, had no wall pores and may function as thermo-hygroreceptors. With the exception of the long subtype of s. trichodea which was recorded only on the male antennae, no other marked sexual differences were recorded in the number and distribution of antennal sensilla in P. tricuspis. These results are discussed in relation to the host location behavior of P. tricuspis, and could facilitate future studies on the neurobiology of olfaction in decapitating phorid flies. PMID- 17869529 TI - Study of natural radioactivity and the state of radioactive disequilibrium in U series for rock samples, North Eastern Desert, Egypt. AB - Twenty rock samples collected from North Eastern Desert in Egypt have been investigated. Natural radionuclide contents have been measured by gamma-ray spectrometry employing a shielded HPGe detector. The activities of (238)U, (232)Th and (40)K have been determined in Bq/kg dry weight. The absorbed dose rate of gamma radiation ranged from 100.48 to 22,140.53 nGy/h. The representative external hazard index values (H(ex)) for the corresponding samples were estimated. In the present work, the state of radioactive disequilibrium in the U series at Wadi Baligh area was studied. The activity ratios between (226)Ra/(214)Pb and (214)Pb/(214)Bi were measured. The thorium-to-uranium concentration ratios (Clark value) were also estimated. PMID- 17869530 TI - Production and separation of non-carrier-added 86Y from enriched 86Sr targets. AB - The metallic radionuclide (86)Y was produced by irradiation of enriched (86)SrCO(3) on a low-energy proton-only cyclotron. Irradiations up to 20 microA for 2h were performed with 11 MeV protons using a water-cooled target mounting with circulating chilled helium. Experimental thick target yields of 26.7 mCi/microA yielded 24 mCi of (86)Y in 2h of bombardment at 10 microA. The difference in solubility products between Y(OH)(3) and Sr(OH)(2) allows the separation of (86)Y from an alkaline strontium solution by using filter paper with an overall yield of 88 +/- 3%. The concentration of Sr in the final product was found to be on the order of 15 ppm when using 200mg of target material as determined by ICP-MS analysis. The reactivity of (86)Y was determined to be on the order of 1.5 +/- 0.8 Ci/micromol of DOTA. The enriched target material was recovered and converted to its original chemical form with an overall efficiency >90%. PMID- 17869531 TI - Construction of the congenitally missing columella in midline clefts. AB - BACKGROUND: Repair of the rare median cleft lip occurring with agenesis of the columella is a challenge as there is a major deficiency of skin and underlying structures. MATERIAL AND METHODS: Over a 23- year period, five children underwent construction of a columella. A new surgical technique was designed for this: an internal dorsal nasal flap was used to create a cutaneous-cartilaginous flap inside the nasal dome, and was then sutured inferiorly against a superior triangle of the repaired median cleft lip. RESULTS: Projective nasal growth could be seen in three of the five surgically constructed columellae in whom the medium term results could be evaluated. CONCLUSION: Five holoprosencephaly cases, all with a median cleft lip and agenesis of the columella, underwent a median cleft lip repair and the creation of a columella by means of an internal nasal dorsal skin flap procedure. PMID- 17869533 TI - Is unilateral brain regional perfusion neurologically safe during congenital aortic arch surgery? AB - OBJECTIVE: This study was conducted to demonstrate that unilateral brain regional perfusion during congenital aortic arch anomaly surgery is neurologically safe. METHODS: Fifteen patients who were diagnosed with congenital aortic arch anomaly between June 2004 and May 2006 were enrolled in this study. The mean age and body weight of the enrolled patients were 40.3+/-35.9 days and 3.7+/-1.0 kg, respectively. Underlying diseases included coarctation of the aorta (12) and an interrupted aortic arch (3). The pre- and postoperative neurological state of each patient was evaluated by a neurologist using an electroencephalogram and brain SPECT. During the operation, unilateral brain regional perfusion was performed using innominate arterial cannulation. Near-infrared spectroscopy (NIRS) and transcranial Doppler ultrasonographic evaluation of the cerebral artery was used to monitor the cerebral perfusion state during surgery. After being discharged a neurologist conducted regular follow-up evaluations of the patients to monitor their neurological development. RESULTS: There were no operative mortalities. Based on NIRS data, there were no significant differences between left and right oxygen saturation during regional perfusion (left:right=66.0+/-10.4%:69.8+/-1.0%, p=0.72) or between the pre-regional and regional perfusion period (1. left side pre-regional perfusion:regional perfusion=66.9+/-11.8%:66.0+/-10.4%, p=0.92, 2. right side pre-regional perfusion:regional perfusion=70.2+/-11.1%:69.8+/-10.0%, p=0.96). Additionally, there were no differences between pre- and postoperative findings in EEG and brain SPECT. For 17.5+/-9.0 months of follow-up duration, no patients showed abnormal neurological finding and development. CONCLUSIONS: Unilateral brain regional perfusion in neonates and children may be a useful technique with no significant neurological deficit. PMID- 17869535 TI - Surgical treatment of coarctation in small infants: our experience. PMID- 17869536 TI - Effect of the addition of diammonium citrate to alpha-cyano-4-hydroxycinnamic acid (CHCA) matrix for the detection of phosphorylated peptide in phosphorylation reactions using cell and tissue lysates. AB - The ionization of phosphorylated peptides is usually suppressed by non phosphorylated peptides when alpha-cyano-4-hydroxycinnamic acid (CHCA) is used as a matrix for matrix-assisted laser desorption/ionization-time-of-Flight (MALDI TOF) mass spectrometry analysis. In the present study, we examined the effect of diammonium citrate addition to the CHCA matrix on the detection of phosphorylated peptides. Substrates for protein kinase C (PKC) and c-Src were synthesized and phosphorylated by reaction with cell and tissue lysate samples. The addition of diammonium citrate to the CHCA matrix increased the sensitivity for distinguishing phosphorylated peptides from background noise. However, the effect depended on substrate concentration. PMID- 17869537 TI - Aquaporin-4 independent Kir4.1 K+ channel function in brain glial cells. AB - Functional interaction of glial water channel aquaporin-4 (AQP4) and inwardly rectifying K+ channel Kir4.1 has been suggested from their apparent colocalization and biochemical interaction, and from the slowed glial cell K+ uptake in AQP4-deficient brain. Here, we report multiple lines of evidence against functionally significant AQP4-Kir4.1 interactions. Whole-cell patch-clamp of freshly isolated glial cells from brains of wild-type and AQP4 null mice showed no significant differences in membrane potential, barium-sensitive Kir4.1 K+ current or current-voltage curves. Single-channel patch-clamp showed no differences in Kir4.1 unitary conductance, voltage-dependent open probability or current-voltage relationship. Also, Kir4.1 protein expression and distribution were similar in wild-type and AQP4 null mouse brain and in the freshly isolated glial cells. Functional inhibition of Kir4.1 by barium or RNAi knock-down in primary glial cell cultures from mouse brain did not significantly alter AQP4 water permeability, as assayed by calcein fluorescence quenching following osmotic challenge. These studies provide direct evidence against functionally significant AQP4-Kir4.1 interactions in mouse glial cells, indicating the need to identify new mechanism(s) to account for altered seizure dynamics and extracellular space K+ buffering in AQP4 deficiency. PMID- 17869538 TI - Exceptional overproduction of a functional human membrane protein. AB - Eukaryotic--especially human--membrane protein overproduction remains a major challenge in biochemistry. Heterologously overproduced and purified proteins provide a starting point for further biochemical, biophysical and structural studies, and the lack of sufficient quantities of functional membrane proteins is frequently a bottleneck hindering this. Here, we report exceptionally high production levels of a correctly folded and crystallisable recombinant human integral membrane protein in its active form; human aquaporin 1 (hAQP1) has been heterologously produced in the membranes of the methylotrophic yeast Pichia pastoris. After solubilisation and a two step purification procedure, at least 90 mg hAQP1 per liter of culture is obtained. Water channel activity of this purified hAQP1 was verified by reconstitution into proteoliposomes and performing stopped-flow vesicle shrinkage measurements. Mass spectrometry confirmed the identity of hAQP1 in crude membrane preparations, and also from purified protein reconstituted into proteoliposomes. Furthermore, crystallisation screens yielded diffraction quality crystals of untagged recombinant hAQP1. This study illustrates the power of the yeast P. pastoris as a host to produce exceptionally high yields of a functionally active, human integral membrane protein for subsequent functional and structural characterization. PMID- 17869539 TI - Computational resources for cryo-electron tomography in Bsoft. AB - The Bsoft package [Heymann, J.B., Belnap, D.M., 2007. Bsoft: image processing and molecular modeling for electron microscopy. J. Struct. Biol. 157, 3-18] has been enhanced by adding utilities for processing electron tomographic (ET) data; in particular, cryo-ET data characterized by low contrast and high noise. To handle the high computational load efficiently, a workflow was developed, based on the database-like parameter handling in Bsoft, aimed at minimizing user interaction and facilitating automation. To the same end, scripting elements distribute the processing among multiple processors on the same or different computers. The resolution of a tomogram depends on the precision of projection alignment, which is usually based on pinpointing fiducial markers (electron-dense gold particles). Alignment requires accurate specification of the tilt axis, and our protocol includes a procedure for determining it to adequate accuracy. Refinement of projection alignment provides information that allows assessment of its precision, as well as projection quality control. We implemented a reciprocal space algorithm that affords an alternative to back-projection or real space algorithms for calculating tomograms. Resources are also included that allow resolution assessment by cross-validation (NLOO2D); denoising and interpretation; and the extraction, mutual alignment, and averaging of tomographic sub-volumes. PMID- 17869540 TI - Stereomotion processing in the human occipital cortex. AB - Although a high proportion of the motion selective cells in primate motion area, MT, are disparity-selective, there is no convincing evidence for cells in this area specific to stereomotion-in-depth and the neural basis of stereomotion processing remains obscure. With functional magnetic resonance imaging (fMRI), we identify an occipito-temporal region activated by cyclopean stereomotion-in-depth stimulation, centered anterior to the human motion complex hMT+. This discovery suggests a reconceptualization of the architecture of the motion complex to incorporate the processing of motion in the third dimension. PMID- 17869541 TI - Am I safe? The ventrolateral prefrontal cortex 'detects' when an unpleasant event does not occur. AB - The ventrolateral prefrontal cortex (VLPFC) is implicated in contingency detection and the evaluation of emotionally significant stimuli. However, the mechanisms whereby an individual can effectively avoid painful or unpleasant events are not well understood. We therefore examined whether the absence of an unpleasant somatosensory stimulus could evoke a response in the human VLPFC as a correlate of contingency detection (the feeling that "I am safe") without any immediately preceding stimulus. In a differential trace-conditioning paradigm, the unpleasant stimulus followed the partially reinforced stimulus in 50% of trials after 3 s; it never occurred after the nonreinforced stimulus. High resolution DC electroencephalography, current source density mapping, and spatio temporal source analysis were performed. After the nonreinforced stimulus, a highly significant negativity over the VLPFC began about a second after the time for the unpleasant stimulus to occur had passed. We concluded that the VLPFC can be activated merely by a sequence of stimuli (with long interstimulus intervals) without any directly preceding stimulus, provided that this sequence creates the expectation that at a certain time an unpleasant stimulus might occur. This mechanism might allow for the detection of conditions under which harmful events could be avoided. Moreover, in reinforced trials, we found a highly significantly lateralized negativity (N700) that outlasted the strong, unpleasant somatosensory stimulus for about a second. Topography and source analysis pointed to prolonged activation of the somatosensory system. This processing stage preceded activation of the VLPFC. We concluded that N700 might provide important insights into the time course of somatosensory memory traces. PMID- 17869542 TI - Diffusion-based spatial priors for imaging. AB - We describe a Bayesian scheme to analyze images, which uses spatial priors encoded by a diffusion kernel, based on a weighted graph Laplacian. This provides a general framework to formulate a spatial model, whose parameters can be optimized. The application we have in mind is a spatiotemporal model for imaging data. We illustrate the method on a random effects analysis of fMRI contrast images from multiple subjects; this simplifies exposition of the model and enables a clear description of its salient features. Typically, imaging data are smoothed using a fixed Gaussian kernel as a pre-processing step before applying a mass-univariate statistical model (e.g., a general linear model) to provide images of parameter estimates. An alternative is to include smoothness in a multivariate statistical model (Penny, W.D., Trujillo-Barreto, N.J., Friston, K.J., 2005. Bayesian fMRI time series analysis with spatial priors. Neuroimage 24, 350-362). The advantage of the latter is that each parameter field is smoothed automatically, according to a measure of uncertainty, given the data. In this work, we investigate the use of diffusion kernels to encode spatial correlations among parameter estimates. Nonlinear diffusion has a long history in image processing; in particular, flows that depend on local image geometry (Romeny, B.M.T., 1994. Geometry-driven Diffusion in Computer Vision. Kluwer Academic Publishers) can be used as adaptive filters. This can furnish a non stationary smoothing process that preserves features, which would otherwise be lost with a fixed Gaussian kernel. We describe a Bayesian framework that incorporates non-stationary, adaptive smoothing into a generative model to extract spatial features in parameter estimates. Critically, this means adaptive smoothing becomes an integral part of estimation and inference. We illustrate the method using synthetic and real fMRI data. PMID- 17869543 TI - Low-frequency fluctuations in the cardiac rate as a source of variance in the resting-state fMRI BOLD signal. AB - Heart rate fluctuations occur in the low-frequency range (<0.1 Hz) probed in functional magnetic resonance imaging (fMRI) studies of resting-state functional connectivity and most fMRI block paradigms and may be related to low-frequency blood-oxygenation-level-dependent (BOLD) signal fluctuations. To investigate this hypothesis, temporal correlations between cardiac rate and resting-state fMRI signal timecourses were assessed at 3 T. Resting-state BOLD fMRI and accompanying physiological data were acquired and analyzed using cross-correlation and regression. Time-shifted cardiac rate timecourses were included as regressors in addition to established physiological regressors (RETROICOR (Glover, G.H., Li, T.Q., Ress, D., 2000. Image-based method for retrospective correction of physiological motion effects in fMRI: RETROICOR. Magn Reson Med 44, 162-167) and respiration volume per unit time (Birn, R.M., Diamond, J.B., Smith, M.A., Bandettini, P.A., 2006b. Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI. NeuroImage 31, 1536-1548). Significant correlations between the cardiac rate and BOLD signal timecourses were revealed, particularly negative correlations in gray matter at time shifts of 6-12 s and positive correlations at time shifts of 30-42 s (TR=6 s). Regressors consisting of cardiac rate timecourses shifted by delays of between 0 and 24 s explained an additional 1% of the BOLD signal variance on average over the whole brain across 9 subjects, a similar additional variance to that explained by respiration volume per unit time and RETROICOR regressors, even when used in combination with these other physiological regressors. This suggests that including such time-shifted cardiac rate regressors will be beneficial for explaining physiological noise variance and will thereby improve the statistical power in future task-based and resting-state fMRI studies. PMID- 17869544 TI - Relationships of Anagallis foemina and A. arvensis (Myrsinaceae): new insights inferred from DNA sequence data. AB - We investigated the relationship between Anagallis arvensis and A. foemina using nuclear and plastid molecular data. Information from the nuclear rDNA internal transcribed spacer (ITS) region and four different chloroplast loci; ndhF, trnL F, rpl16, and rps16 was analysed using both parsimony and Bayesian inference. Anagallis foemina was found to be most closely related to the perennial A. monelli, and not to A. arvensis. The existence of two different cpDNA haplotypes was revealed; one shared by Anagallis foemina, A. monelli, A. platyphylla, and one A. arvensis individual, while all other investigated A. arvensis individuals shared the second haplotype. Ancestral cpDNA polymorphism within Anagallis arvensis or hybridization are possible explanations, however, information in ITS data is too scarce to falsify any of these hypotheses. PMID- 17869545 TI - Surface ultrastructure and mechanical property of human chondrocyte revealed by atomic force microscopy. AB - OBJECTIVE: The mechanical properties of chondrocytes influence maintenance of the articular cartilage extracellular matrix. To differentiate the mechanical properties of chondrocytes between a young, normal modulus and an old, osteoarthritic (OA) modulus, we used an atomic force microscope (AFM) to probe the surface ultrastructure and to measure their adhesion force and stiffness. METHODS: We directly visualized a single chondrocyte cell by using AFM and quantitatively measured the dimensions of the cells. RESULTS: Profiles displayed heights of 1026+/-203 and 1668+/-352 nm for old and young cells, respectively. Contour maps revealed differences in the sizes and structures of the two groups. Mean calculated adhesion forces differed between normal and OA chondrocytes (7.06+/-3.35 and 2.97+/-1.82 nN, respectively), as did calculated stiffness values (0.0960+/-0.009 and 0.0347+/-0.005 N/m, respectively). CONCLUSION: These findings suggested that the mechanical properties of normal chondrocytes substantially differed from those of OA chondrocytes. We believe this study represents the first direct characterization of the surface ultrastructure and mechanical measurements of human chondrocytes between normal and OA stages. This new approach could be a useful technique for investigating age-related changes in the properties of human chondrocytes. PMID- 17869546 TI - Femoral sulcus angle and increased patella facet cartilage volume in an osteoarthritic population. AB - OBJECTIVE: The patellofemoral joint is an example of an incongruent articulation commonly affected by osteoarthritis (OA). The relationship between femoral sulcus angle and the development and progression of patellofemoral OA is unclear. The aim of this study was to examine the relationship between the femoral sulcus angle at baseline and patella cartilage volume at baseline and at 2-year follow up among community based adults with established knee OA. METHODS: One hundred subjects had magnetic resonance imaging of their symptomatic knee at baseline and at 2-year follow-up. From these images, patella cartilage volume was determined. Radiographic skyline views of the patellofemoral joint were taken at baseline to measure the femoral sulcus angle. RESULTS: For every 1 degrees increase in the femoral sulcus angle (i.e., as the sulcus angle became more shallow) there was an associated 9.1mm3 (95% CI 3.1, 15.0) increase in medial patella cartilage volume at baseline (P=0.003). There was a similar trend that approached statistical significance between the femoral sulcus angle and the lateral patella facet cartilage volume at baseline (P=0.09). There was no association between the femoral sulcus angle at baseline and the change in patella cartilage volume over 2 years in either patellofemoral compartment. CONCLUSION: These results infer that the femoral sulcus angle is a cross-sectional determinant of the amount of patella cartilage, but is not a major determinant of the annual change of patella cartilage volume among people with knee OA. These data suggest that a shallower sulcus in the context of established OA may be an advantageous anatomical variant. Further longitudinal studies are required to determine the role of the femoral sulcus angle in OA. PMID- 17869547 TI - Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning: an update. AB - Haploidentical hematopoietic cell transplantation (HHCT) after high dose conditioning with CD34-selected stem cells has been complicated by high regimen related toxicities, slow engraftment and delayed immune reconstitution leading to increased treatment related mortality (TRM). A new regimen using reduced intensity conditioning (RIC) and graft CD3/CD19 depletion with anti-CD3 and anti CD19 coated microbeads on a CliniMACS device may allow HHCT with lower toxicity and faster engraftment. CD3/CD19 depleted grafts not only contain CD34+ stem cells but also CD34 negative progenitors, natural killer, graft facilitating and dendritic cells. RIC was performed with fludarabine (150-200 mg/m(2)), thiotepa (10 mg/kg), melphalan (120 mg/m(2)) and OKT-3 (5 mg/day, day -5 to +14) and no posttransplant immunosuppression. Twenty nine patients (median age=42 (range, 21 59) years) have been transplanted with this regimen. Diagnosis were AML (n=16), ALL (n=7), NHL (n=3), MM (n=2) and CML (n=1). Patients were "high risk" with refractory disease or relapse after preceding HCT. The CD3/CD19 depleted haploidentical grafts contained a median of 7.6x10(6) (range, 3.4-17x10(6)) CD34+ cells/kg, 4.4x10(4) (range, 0.006-44x10(4)) CD3+ T cells/kg and 7.2x10(7) (range, 0.02-37.3x10(7)) CD56+ cells/kg. Donor-recipient KIR-ligand-mismatch was found in 19 of 29 patients. The regimen was well tolerated with maximum acute toxicity being grade 2-3 mucositis. Because of severe neurotoxicity in 4 patients treated with 200 mg/m(2) fludarabine, the dose was reduced to 150 mg/m(2). Engraftment was rapid with a median time to >500 granulocytes/microL of 12 (range, 10-21) days, >20,000 platelets/microL of 11 (range, 7-38) days and full donor chimerism after 2-4 weeks in all patients. Incidence of grade II-IV degrees GVHD was 48% with grade II degrees =10, III degrees =2 and IV degrees =2. One patient, who received the highest T-cell dose, developed lethal grade IV GVHD. TRM in the first 100 days was 6/29 (20%) with deaths due to idiopathic pneumonia syndrome (n=1), mucormycosis (n=1), pneumonia (n=3) or GVHD (n=1). Overall survival is 9/29 patients (31%) with deaths due to infections (n=7), GVHD (n=1) and relapse (n=12) with a median follow-up of 241 days (range, 112-1271). In conclusion, this regimen is promising in high risk patients lacking a suitable donor, and a prospective phase I/II study is ongoing. PMID- 17869548 TI - Adoptive cellular therapy for cytomegalovirus infection following allogeneic stem cell transplantation using virus-specific T cells. AB - Adoptive transfer of virus-specific T cells offers the potential for accelerating reconstitution of antigen-specific immunity and limiting the morbidity and mortality of viral infections following allogeneic haematopoietic stem cell transplantation. However, the logistics of producing virus-specific T cells and the risk of inducing graft-versus-host disease secondary to the infusion of alloreactive clones have limited the application of cellular therapies. We report the results in patients of pre-emptive and prophylactic therapy with cytomegalovirus-specific T cells. Cells were administered at early time points following transplantation (when the risk of GVHD is greatest) either prophylactically or following the detection of CMV DNA by a PCR-based surveillance technique. Massive in vivo expansions of CMV-specific cytotoxic T lymphocytes (3-5 log) were observed in patients within days of adoptive transfer. Viral titers were decreasing within 5 days, in some patients the T-cell receptor CDR3 lengths of CMV-specific CTL expanding in vivo were identical to those of the transferred cells. A low incidence of late cytomegalovirus reactivation was seen and no significant toxicities were observed. Our findings indicate that application of cell lines generated by either short-term in vitro cultures or by direct selection using gamma-capture, which allow expansion of both CD4(+) and CD8(+) virus-specific T cells, is both feasible and effective in a clinical environment. These simple in vitro methodologies should allow widespread application of adoptive transfer of virus-specific T cells. PMID- 17869550 TI - Application of multipotent mesenchymal stromal cells in pediatric patients following allogeneic stem cell transplantation. AB - Multipotent mesenchymal stromal cells (MSC) have immunomodulatory effects. The aim of this study was to demonstrate safety and feasibility of MSC transfusion in pediatric patients who had undergone allogeneic stem cell transplantation from MMFD, MUD, MMUD and MSD. Patients with posttransplant complications based on deregulated immune effector cells who may benefit from an immunomodulatory effect of MSC had been selected. MSC were isolated from the hematopoietic stem cell donors in five cases and from a third party parental donor in two cases. We transfused ex vivo-expanded MSC in 11 doses into seven pediatric patients. Cell doses were escalated based on availability from 0.4x10(6) to 3.0x10(6) per kg bodyweight No adverse effects were detected with a maximum follow-up of 29 months. One out of three patients showed slight improvement of chronic GVHD. Two patients with severe acute GvHD did not progress to cGvHD. One patient received MSC to stabilize graft function after secondary haploidentical transplantation. One patient recovered from trilineage failure due to severe hemophagocytosis. This is the first case of a pediatric patient treated with MSC for trilineage failure after haploidentical stem cell transplantation from her father. We report the first series of 11 transfusions of expanded MSC in pediatric patients with immunological complications after allogeneic transplantation. Transfusion of MSC was safe and encouraging improvements in some patients were observed. PMID- 17869549 TI - Soluble hemojuvelin is released by proprotein convertase-mediated cleavage at a conserved polybasic RNRR site. AB - As the principal iron-regulatory hormone, hepcidin plays an important role in systemic iron homeostasis. The regulation of hepcidin expression by iron loading appears to be unexpectedly complex and has attracted much interest. The GPI linked membrane protein hemojuvelin (GPI-hemojuvelin) is an essential upstream regulator of hepcidin expression. A soluble form of hemojuvelin (s-hemojuvelin) exists in blood and acts as antagonist of GPI-hemojuvelin to downregulate hepcidin expression. The release of s-hemojuvelin is negatively regulated by both transferrin-bound iron (holo-Tf) and non-transferrin-bound iron (FAC), indicating s-hemojuvelin could be one of the mediators of hepcidin regulation by iron. In this report, we investigate the proteinase involved in the release of s hemojuvelin and show that s-hemojuvelin is released by a proprotein convertase through the cleavage at a conserved polybasic RNRR site. PMID- 17869551 TI - Endothelial nitric oxide production is tightly coupled to the citrulline-NO cycle. AB - Nitric oxide (NO) is an important vasorelaxant produced along with L-citrulline from L-arginine in a reaction catalyzed by endothelial nitric oxide synthase (eNOS). Previous studies suggested that the recycling of L-citrulline to L arginine is essential for NO production in endothelial cells. However, there is no direct evidence demonstrating the degree to which the recycling of L citrulline to L-arginine is coupled to NO production. We hypothesized that the amount of NO formed would be significantly higher than the amount of L-citrulline formed due to the efficiency of L-citrulline recycling via the citrulline-NO cycle. To test this hypothesis, endothelial cells were incubated with [14C]-L arginine and stimulated by various agents to produce NO. The extent of NO and [14C]-L-citrulline formation were simultaneously determined. NO production exceeded apparent L-citrulline formation of the order of 8 to 1, under both basal and stimulated conditions. As further support, alpha-methyl-DL-aspartate, an inhibitor of argininosuccinate synthase (AS), a component of the citrulline-NO cycle, inhibited NO production in a dose-dependent manner. The results of this study provide evidence for the essential and efficient coupling of L-citrulline recycling, via the citrulline-NO cycle, to endothelial NO production. PMID- 17869552 TI - Cytokine expression by peripheral blood neutrophils from heaves-affected horses before and after allergen challenge. AB - Heaves, also known as recurrent airway obstruction, is a common condition of horses characterised by pulmonary neutrophilia and reversible airway obstruction. This study evaluated the role of neutrophils in producing cytokines and chemokines that might be involved in the recruitment and activation of inflammatory cells in horses with heaves. Peripheral neutrophils were isolated from heaves-affected (n = 9) and control (n = 4) horses before and after 5 h of natural inhalation challenge. Expression of mRNA of two pro-inflammatory cytokines, tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta, along with two chemokines, IL-8 and macrophage inflammatory protein (MIP)-2, was evaluated. After exposure to mouldy hay, horses with heaves had significant airway obstruction and increased numbers of neutrophils in bronchoalveolar lavage samples, compared to control horses. However, there were no differences in the expression of mRNAs of TNF-alpha, IL-1beta, IL-8 and MIP-2 between the two groups, suggesting that the release of cytokines and chemokines by peripheral blood neutrophils is not necessary for the development of heaves. PMID- 17869553 TI - Emergence of a highly pathogenic porcine reproductive and respiratory syndrome virus in the Mid-Eastern region of China. AB - Herds of pigs in the Mid-Eastern region of China have experienced recent outbreaks of a severe form of porcine reproductive and respiratory syndrome (PRRS) characterised by high fever and morbidity and mortality in animals of different ages. Eighty-one herds were diagnosed with PRRS virus (PRRSV) infection from June to December 2006 on the basis of clinical signs, pathological findings and reverse transcriptase polymerase chain reaction (RT-PCR). Twenty strains of PRRSV were isolated from 20 herds in six provinces. Following experimental inoculation, one isolate, designated SY0608, caused 100% morbidity and 25-50% mortality in 30-, 65- and 105-day-old pigs and the birth of stillborn and weak piglets from affected sows. The ORF5 gene had 99.5-99.8% nucleotide and 99-100% derived amino acid sequence identities among SY0608 and five other field isolates, but only 89.4% and 88.6% identities, respectively, with VR-2332, the prototypic North American isolate. The 2850bp Nsp2 gene of SY0608 had 79.4% nucleotide and 74.9% derived amino acid sequence identities with VR-2332; deletions of 1 and 29 amino acids corresponded to positions 480 and 531-559 of strain VR-2332, respectively. These findings demonstrated that a new highly pathogenic Northern American type PRRSV has spread widely in the Mid-Eastern region of China. PMID- 17869554 TI - Differential alterations in the ability of bovine neutrophils to generate extracellular and intracellular reactive oxygen species during the periparturient period. AB - The periparturient period of a dairy cow is associated with increased incidence and/or severity of certain infectious diseases, including mastitis. It is believed that the heightened physiological demands of calving and initiation of milk production contribute to a state of immunosuppression during this period. Previous studies have indicated that neutrophil production of reactive oxygen species (ROS), which is a critical element of the host innate immune response to bacterial infection, is impaired in the 1-2week period following calving. However, whether there is comprehensive inhibition of ROS production or selective inhibition of particular ROS remains unknown. The present study provides evidence that neutrophils isolated from cows (n=20) after calving have an increased capacity to generate intracellular ROS and an impaired ability to release extracellular superoxide anion and hydrogen peroxide. PMID- 17869555 TI - Detection of pathogenic leptospires in urine from naturally infected cattle by nested PCR. AB - A nested polymerase chain reaction (PCR) using primers from the LipL32 sequence of Leptospira spp. was used to detect shedding of pathogenic leptospires in urine from naturally infected cattle. Amplicons (497bp) were obtained from 21 pathogenic reference serovars belonging to four species (L. interrogans, L. borgpetersenii, L. santarosai, L. kirschneri). DNA was amplified from 26/30 urine samples taken from cattle with suspected leptospirosis and from leptospires cultivated from 10 of these samples. The limit of detection of DNA in the clinical samples was 200pg and the nested PCR detected all pathogenic reference serovars of Leptospira spp. tested. No PCR products were amplified using DNA from other common bacterial species from the bovine urogenital tract or urine, or from the non-pathogenic L. biflexa Andamana serovar. The nested PCR exhibited high specificity and sensitivity for detection of pathogenic serovars in urine from cattle. PMID- 17869556 TI - Neuroimaging correlation with neurological severity in tuberous sclerosis complex. AB - OBJECTIVE: To delineate the relationship between neurological severity and neuroimage of lesion load including specific topography of supratentorial cortical tubers and white matter lesions in tuberous sclerosis complex (TSC). METHODS: Twenty-five TSC patients more than 2 years of age who underwent conventional and fluid-attenuated inversion recovery sequence (FLAIR) magnetic resonance imaging (MRI) were retrospectively studied. Neurological severity score was designated for three items: seizure, developmental delay and/or mental retardation, and autism. A neuroimaging scoring system was designed to evaluate the load of the cerebrum lesions with respect to location and size of cortical tubers and white matter lesions based on FLAIR MRI. RESULTS: A linear trend was observed between MRI lesion score and neurological severity score (r=0.511; p=0.009). The lesion score in the left temporal lobe has positive correlation to neurological severity score (r=0.609; p=0.001). CONCLUSIONS: The brain lesion load was positively correlated with neurological prognosis in TSC patients. Patients with larger lesion load in the left temporal lobe may be correlated with increased neurological severity in right-handed patients with TSC. PMID- 17869557 TI - The effects of skin-to-skin contact during acute pain in preterm newborns. AB - BACKGROUND AND PURPOSE: Several promising non-pharmacological interventions have been developed to reduce acute pain in preterm infants including skin-to-skin contact between a mother and her infant. However, variability in physiological outcomes of existing studies on skin-to-skin makes it difficult to determine treatment effects of this naturalistic approach for the preterm infant. The aim of this study was to test the efficacy of mother and infant skin-to-skin contact during heel prick in premature infants. METHOD: Fifty nine stable preterm infants (born at least 30 weeks gestational age) who were undergoing routine heel lance were randomly assigned to either 15 min of skin-to-skin contact before, during and following heel prick (n=31, treatment group), or to regular care (n=28, control group). Throughout the heel lance procedure, all infants were assessed for change in facial action (NFCS), behavioral state, crying, and heart rate. RESULTS: Statistically significant differences were noted between the treatment and control groups during the puncture, heel squeeze and the post phases of heel prick. Infants who received skin-to-skin contact were more likely to show lower NFCS scores throughout the procedure. Both groups of infants cried and showed increased heart rate during puncture and heel squeeze although changes in these measures were less for the treated infants. CONCLUSIONS: Skin-to-skin contact promoted reduction in behavioral measures and less physiological increase during procedure. It is recommended that skin-to-skin contact be used as a non pharmacologic intervention to relieve acute pain in stable premature infants born 30 weeks gestational age or older. PMID- 17869559 TI - Spectroscopic imaging from spatially-encoded single-scan multidimensional MRI data. AB - We have recently proposed a protocol for retrieving multidimensional magnetic resonance images within a single scan, based on a spatial encoding of the spin interactions. This methodology relies on progressively dephasing spin coherences throughout a sample; for instance, by sweeping a radiofrequency pulse in the presence of a magnetic field gradient. When spins are suitably refocused by a second (acquisition) field gradient, this yields a time-domain signal reflecting in its magnitude the spatial distribution of spins throughout the sample. It is hereby shown that whereas the absolute value of the resulting signals conveys such imaging information, the hitherto unutilized phase modulation of the signal encodes the chemical shift offsets of the present speciae. Spectroscopically resolved multidimensional images can thereby be retrieved in this fashion at no additional expense in either experimental complexity, sensitivity or acquisition time--simply by performing an additional analysis of the collected data. The resulting approach to single-scan spectroscopic imaging can also incorporate "RF shimming" compensating abilities, capable of providing high-resolution spectral and high-definition imaging data even under the presence of substantial magnetic field inhomogeneities. The principles of these methodologies as applied to spectroscopic imaging are briefly reviewed and compared against the background of traditional Fourier-based single-scan spectroscopic imaging protocols. Demonstrations of these new multidimensional spectroscopic MRI experiments on simple phantoms are also given. PMID- 17869558 TI - Pursuing structure in microcrystalline solids with independent molecules in the unit cell using 1H-13C correlation data. AB - The (1)H-(13)C solid-state NMR heteronuclear correlation (HETCOR) experiment is demonstrated to provide shift assignments in certain powders that have two or more structurally independent molecules in the unit cell (i.e. multiple molecules per asymmetric unit). Although this class of solids is often difficult to characterize using other methods, HETCOR provides both the conventional assignment of shifts to molecular positions and associates many resonances with specific molecules in the asymmetric unit. Such assignments facilitate conformational characterization of the individual molecules of the asymmetric unit and the first such characterization solely from solid-state NMR data is described. HETCOR offers advantages in sensitivity over prior methods that assign resonances in the asymmetric unit by (13)C-(13)C correlations and therefore allows shorter average analysis times in natural abundance materials. The (1)H (13)C analysis is demonstrated first on materials with known shift assignments from INADEQUATE data (santonin and Ca(OAc)(2) phase I) to verify the technique and subsequently is extended to a pair of unknown solids: (+)-catechin and Ca(OAc)(2) phase II. Sufficient sensitivity and resolution is achieved in the spectra to provide assignments to one of the specific molecules of the asymmetric unit at over 54% of the sites. PMID- 17869560 TI - Assessing signal enhancement in distant dipolar field-based sequences. AB - The possibility of improving the signal-to-noise efficiency of NMR signal refocused by long-range dipolar interactions has been discussed recently [R.T. Branca, G. Galiana, W.S. Warren, Signal enhancement in CRAZED experiments, J. Magn. Reson. 187 (2007) 38-43]. For systems where T(1)>>T(2), by including an extra radio-frequency pulse in a standard CRAZED sequence, it is possible to increase the available signal by exploiting its sensitivity to T(1) relaxation. Here, we use analytical calculations to investigate the source of this improved signal and determine the maximum enhancement provided by the method. PMID- 17869561 TI - Absence of KCNQ1-dependent K+ fluxes in proximal tubular cells of frog kidney. AB - The present study was designed to investigate the functional significance of KCNQ1-mediated K+ secretory fluxes in proximal tubular cells of the frog kidney. To this end, we investigated the effects on rapid depolarization and slow repolarization of the peritubular membrane potential after luminal addition of L phenylalanine or L-alanine plus/minus KCNQ1 channel blockers. Perfusing the lumen with 10 mmol/L L-phenylalanine plus/minus luminal 293B, a specific blocker of KCNQ1, did not modify the rapid depolarization and the rate of slow repolarization. Perfusing the lumen with 10 mmol/L L-alanine plus/minus luminal HMR-1556, a more potent KCNQ1 channel blocker, did not also alter the rapid depolarization and the rate of slow repolarization. Pretreatment (1 h) of the lumen with HMR-1556 also failed to modify rapid depolarization and rate of slow repolarization upon luminal 10 mmol/L L-alanine. Perfusing the lumen with 1 mmol/L L-alanine plus/minus luminal HMR-1556 did not change the rapid depolarization and the rate of slow repolarization. The pretreatment (1 h) with luminal HMR-1556 did not modify the rapid depolarization and the rate of slow repolarization upon luminal 1 mmol/L L-alanine. The pretreatment (1 h) of the lumen with HMR-1556 did not change transference number for K+ of peritubular cell membrane. Finally, luminal barium blunted the rapid depolarization upon application of luminal 1 mmol/L L-alanine. RT-PCR showed that KCNQ1 mRNA was not expressed in frog kidney. In conclusion, the KCNQ1-dependent K+ secretory fluxes are absent in proximal tubule of frog kidney. PMID- 17869562 TI - Oxygen consumption as related to the development of the extraembryonic membranes and cardiovascular system in the European pond turtle (Emys orbicularis) embryogenesis. AB - The rate of oxygen consumption (V(O2)), embryo mass, distribution and mass of the chorioallantoic membrane (CAM), heart rate (HR), heart mass, and amnion rhythmic contractions (ARC) were studied in eggs of the European pond turtle (Emys orbicularis) incubated at 28 degrees C for 62.5+/-0.3 days. The V(O2) rapidly increased beginning from incubation day 19 (D19) to a maximum on D50 and then decreased until pipping. The rapid V(O2) rise was correlated with an increase in the CAM surface and mass, heart mass, and ARC amplitude, whereas the functional parameters such as HR and ARC frequency remained unchanged. The drop in V(O2) before pipping was accompanied by a decrease in HR, while the heart and CAM masses were almost constant. In the cases of short-term temperature deviations of +/-3 degrees C from 28 degrees C, changes in (O2) were significant until D50 and nonsignificant after that, the changes in ARC frequency and HR being significant at all stages studied. Thus, the developmental V(O2) changes were contributed mainly by the slow morphogenetic processes during D19-D50, whereas changes in functional parameters began to play a role at later stages. The response to temperature fluctuations was mediated by a rapid change in functional parameters at all these stages. PMID- 17869563 TI - A metabolic flux analysis to study the role of sucrose synthase in the regulation of the carbon partitioning in central metabolism in maize root tips. AB - In order to understand the role of sucrose synthase (SuSy) in carbon partitioning, metabolic fluxes were analyzed in maize root tips of a double mutant of SuSy genes, sh1 sus1 and the corresponding wild type, W22. [U-(14)C] glucose pulse labeling experiments permitted the quantification of unidirectional fluxes into sucrose, starch and cell wall polysaccharides. Isotopic steady-state labeling with [1-(13)C]-, [2-(13)C]- or [U-(13)C]-glucose followed by the quantification by (1)H-NMR and (13)C-NMR of enrichments in carbohydrates and amino acids was also performed to determine 29 fluxes through central metabolism using computer-aided modeling. As a consequence of the suppression of SUS1 and SH1 isozymes, maize root tips diameter was significantly decreased and respiratory metabolism reduced by 30%. Our result clearly established that, in maize root tips, starch is produced from ADP-Glc synthesized in the plastid and not in the cytosol by sucrose synthase. Unexpectedly, the flux of cell wall synthesis was increased in the double mutant. This observation indicates that, in maize root tips, SH1 and SUS1 are not specific providers for cellulose biosynthesis. PMID- 17869564 TI - [Salvage radiotherapy in rising PSA after radical prostatectomy]. AB - Salvage radiotherapy after radical prostatectomy can be delivered either in case of biochemical recurrence or in situation of clinical relapse. In this last case, results are poor regarding disease-free survival but quite interesting regarding the local control rate. The best situation for salvage radiotherapy is still the rising PSA case: half of the patients can be in complete remission at 5 years after 65 Gy radiotherapy. The role of hormone therapy combined with salvage radiotherapy is still under investigation. PMID- 17869565 TI - Atheroma and systemic lupus erythematosus. AB - Epidemiologic data indicate a large increase in cardiovascular risk in patients with systemic lupus erythematosus (SLE). Non-invasive investigations show increases in intima-media thickness, carotid plaque, and coronary artery calcifications in patients with SLE, compared to controls. Conventional cardiovascular risk factors may fail to fully explain the high cardiovascular risk in SLE patients. Immunological disturbances and inflammation may indirectly contribute to the risk of cardiovascular disease by inducing dyslipidemia and/or insulin resistance. The potential role for glucocorticoid therapy is controversial. Effective control of the disease would be expected to decrease the cardiovascular morbidity and mortality rates. Careful attention should be given to controlling conventional risk factors such as obesity, smoking, and physical inactivity. Hypertension and/or dyslipidemia should be treated optimally. The appropriateness of antiplatelet therapy should be assessed. PMID- 17869566 TI - [Aneurysmal bone cysts of the metacarpals and phalanges of the hand. A 6 case series and literature review]. AB - Aneurysmal bone cysts arising from tubular bones of the hand occur very rarely and require particular diagnostic and therapeutic management techniques. The authors report the diagnostic and surgical management of a monocentric case series of six aneurysmal bone cysts involving the phalangeal and metacarpal bones. In addition to hightlighting the use of diagnostic MRI and biopsy prior to surgical intervention, the authors describe the favourable outcome of curetage with and without the use of bone graft. An aggressive treatment approach such as cryotherapy or resection with reconstruction should only be used in cases when the articular surface is involved, when full bone invasion of the phalanx or metacarpal has occurred, or in case of more than one recurrence. PMID- 17869567 TI - [Ethical problems of extreme prematurity: results of a qualitative study with obstetricians and midwives]. AB - OBJECTIVE: Our objective was to explore the practices, attitudes and feelings of obstetricians and midwives in case of extreme prematurity. POPULATION AND METHODS: A qualitative study was conducted as part of a European Concerted Action (EUROBS) in 1999 and 2000 in three tertiary-care maternity units, located in three cities in the northern, southern and central areas of France respectively. Semi-structured, tape-recorded interviews were conducted and were independently analysed by two different researchers using a content analysis. All full-time obstetricians and half of the full-time midwives were eligible for the study. Overall, 17 obstetricians and 30 midwives participated. RESULTS: Both obstetricians and midwives considered that decision-making in case of very preterm births raised ethical problems concerning the mother and the foetus. Despite some birth weight and gestational age criteria defined in advance, management around delivery appeared to be decided on a case-by-case basis. At birth, the neonatologists made the decisions. They were perceived as more inclined than the obstetrical team to initiate intensive care. If the child was born alive, intensive care was started, knowing that it could be withdrawn later, if appropriate. Parents were sometimes involved in decision-making during pregnancy, less frequently at birth or after birth. DISCUSSION AND CONCLUSION: Compared with obstetricians, midwives tended to have a less favourable perception of the neonatologists' practices, and to deplore the lack of parental information and involvement in decision-making. Decisions about the obstetrical management and resuscitation of extremely preterm infants are essentially always made on a case-by-case basis. Parents are sometimes involved in decision-making. Midwives express serious concerns about the current practices. PMID- 17869568 TI - [The experience of in vitro fertilization procedure (IVF)]. AB - OBJECTIVE: In vitro fertilization (IVF) is long and difficult. Psychopathologic consequences of IVF have been the object of a great deal of research but few have dealt with women experiences. This study examined women experiences through the analysis of qualitative data. PATIENTS AND METHODS: Six women undergoing IVF took part in a semi-directive interview. RESULTS: Qualitative analyses of interviews showed the variety of emotions that women experience during IVF. They experience despair, fear, solitude, unfairness, anxiety, anger, guilt but also hope and determination. DISCUSSION AND CONCLUSION: The results of this study underline the need for specific support to help women with this emotional alternation. PMID- 17869569 TI - From genes to shape: regulatory interactions in leaf development. AB - In the past two years novel connections were described between auxin function and transcription factor patterning systems involved in both leaf initiation and elaboration of leaf axial patterning. A cascade of small RNA-based regulatory steps was suggested to facilitate delimitation of cell types comprising the upper versus lower parts of the leaf. Developmental regulation of cellular growth emerged as a crucial component in regulation of leaf form with TCP and CUC2 transcription factors playing a key role in this process. Finally, cis-regulatory evolution of developmental genes emerged as a process that likely contributed to diversification of leaf form, while studies in seedless land plants have begun to elucidate the ancestral and derived aspects of leaf development pathways. PMID- 17869570 TI - Action of 1,1-dimethylhydrazine on bacterial cells is determined by hydrogen peroxide. AB - Seven different recombinant bioluminescent strains of Escherichia coli containing, respectively, the promoters katG and soxS (responsive to oxidative damage), recA (DNA damage), fabA (membrane damage), grpE, and rpoE (protein damage) and lac (constitutive expression) fused to the bacterial operon from Photorhabdus luminescens, were used to describe the mechanism of toxicity of 1,1 dimethylhydrazine (1,1-DMH) on bacteria, as well as to determine whether bacteria can sensitively detect the presence of this compound. A clear response to 1,1-DMH was observed only in E. coli carrying the katG'::lux, soxS'::lux, and recA'::lux containing constructs. Preliminary treatment with catalase of the medium containing 1,1-DMH completely diminished the stress-response of the P(katG), P(recA), and P(soxS) promoters. In the strain E. coli (pXen7), which contains a constitutive promoter, the level of cellular toxicity caused by the addition of 1,1-DMH was dramatically reduced in the presence of catalase. It is suggested that the action of 1,1-DMH on bacterial cells is determined by hydrogen peroxide, which is formed in response to reduction of the air oxygen level. PMID- 17869572 TI - Antibacterial functionalization of an experimental self-etching primer by inorganic agents: microbiological and biocompatibility evaluations. AB - Antibacterial activities have been demonstrated on oral bacteria with inorganic antibacterial agents (ABAs) after their incorporations into an experimental self etching primer (ESP) before curing. This study was to assess their biocompatibility and antibacterial activity after curing. Six ABAs were incorporated respectively into ESP for treating specimens. After curing, their bactericidal activities on Streptococcus mutans and influences to the early bacterial colonization were assessed by direct contact and viable count. Systemic toxicity in rats after short-term oral exposure and direct contact cytotoxicity with NIH3T3 fibroblasts were tested. Incorporation of ZnOw AT-83, Longbei antibiotic, Antim-AMS2 or IONPURE-H significantly enhanced the antibacterial effect of ESP after curing, even after 1 month aging. Specimens treated by ESP with ZnOw AT-83, Longbei antibiotic or Antim-AMS2 showed slightly less bacterial adhesion than control. Animal experiments revealed neither toxic signs nor significant differences in body weight gain between control and other groups. Cell vitality or proliferation rates were ranged from 76% to 100% with respect to controls. Basic magnesium hypochlorite, ZnOw AT-83 and ZnOw AT-88 were less toxic. Toxicity only observed in areas beneath the specimens and/or in the direct vicinity of the specimen edge. From microbiological and biocompatibility aspects, the tested ABAs can be effectively incorporated in ESP to provide antibacterial activity against S. mutans. ZnOw AT-83 was the most promising one. PMID- 17869571 TI - Comparison of flow cytometry- and microscopy-based methods for measuring micronucleated reticulocyte frequencies in rodents treated with nongenotoxic and genotoxic chemicals. AB - The development of automated flow cytometric (FCM) methods for evaluating micronucleus (MN) frequencies in erythrocytes has great potential for improving the sensitivity, reproducibility, and throughput of the traditional in vivo rodent MN assay that uses microscopy-based methods for data collection. Although some validation studies of the FCM evaluation methods have been performed, a comprehensive comparison of these two data collection methods under routine testing conditions with a variety of compounds in multiple species has not been conducted. Therefore, to determine if FCM evaluation of MN frequencies in rodents was an acceptable alternative to traditional manual scoring methods in our laboratory, we conducted a comparative evaluation of MN-reticulocyte (MN-RET) frequencies determined by FCM- and microscopy-based scoring of peripheral blood and bone marrow samples from B6C3F1 mice and Fisher 344 rats. Four known inducers of MN (cyclophosphamide, ethyl methanesulfonate, vincristine sulfate, acrylamide) were assayed in bone marrow and peripheral blood of both mice and rats. In addition, MN-RET frequencies were measured in bone marrow (microscopy) and peripheral blood (FCM) of mice treated with five nongenotoxic chemicals (S adenosylmethionine chloride, cefuroxime, diphenolic acid, 3-amino-6-methylphenol, pentabromodiphenyl oxide). No significant differences were observed between results obtained by the two methods in either species. These results support the use of FCM for determining MN-RET frequency in rodents after chemical exposure. PMID- 17869574 TI - High-altitude sleep disturbance: results of the Groningen Sleep Quality Questionnaire survey. AB - OBJECTIVE: To assess the Groningen Sleep Quality Scale (GSQS) for evaluation of high-altitude sleep (HAS) disturbance and employ GSQ questionnaire to describe HAS. METHODS: After the first night's stay at the altitude of 3500 m, quality of sleep for 100 participants (age: 29.13+/-11.01 years; 36 females/64 males) was assessed using the self-administered 15-item GSQS translated into Farsi. RESULTS: Mean GSQS score was 5.36+/-4.32; 38 (38%) participants had a score equal to or less than 2, and 46 (46%) participants had a score equal to or more than 6. A Cronbach's alpha of 0.90 was calculated for internal consistency. Waking up several times during the night was the most prevalent complaint during the first night of sleep, and absolute inability to sleep was the most uncommon problem. CONCLUSIONS: HAS disturbance, which involved many of newcomers to a high altitude, had various harmful effects. For HAS research, GSQS was confirmed to be valid and reliable. PMID- 17869573 TI - A further evaluation of the cognitive deficits associated with restless legs syndrome (RLS). AB - BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) is a common sensorimotor disorder that peaks in severity during the night and comes on with rest. As a result, this condition often results in significant chronic sleep loss, especially for those with severe disease. Chronic partial sleep restriction has been associated with conditions such as depression, anxiety, chronic pain, and decline in cognitive function. Furthermore, studies have found that RLS patients suffer from these conditions more than their unaffected peers. Thus, the morbidity rate associated with RLS has often been attributed to the chronic sleep loss that frequently accompanies this condition. However, no study has specifically compared RLS sufferers to otherwise normal sleep-restricted controls in order to assess disease morbidity independent of its sleep deprivation effects. In this study, we compared the cognitive function of RLS patients who were off treatment to sleep-restricted control subjects. SUBJECTS AND METHODS: A novel chronic partial sleep-restriction protocol that utilized a 14-day combined inpatient and outpatient design was implemented in order to test the differences in cognitive functioning between RLS patients and sleep-restricted controls. The brief cognitive battery included instruments assessing general intelligence and global executive function in order to control for baseline cognitive function between the groups, and then the effects of sleep loss were assessed using prefrontal lobe-specific tasks. The final sample consisted of 16 RLS (11 male and 5 female) and 13 sleep-restricted control subjects (7 male and 6 female). RESULTS: In order to examine the differences in cognitive functioning between sleep-restricted controls and RLS subjects, independent samples t-tests were conducted. RLS subjects performed significantly better on both the Letter Fluency (t=2.13, p<0.05) and Category Fluency (t=2.42, p<0.05) than sleep-restricted controls. CONCLUSIONS: RLS subjects performed better than the sleep-restricted controls on two tasks that are particularly sensitive to sleep loss. Although previous studies suggest that sleep deprivation may impact the cognitive function of those with RLS, our data suggests that RLS subjects may show a relative degree of sleep loss adaptation. Future investigations that more closely match the sleep loss pattern of RLS subjects to controls are warranted in order to explore these potential traits further. PMID- 17869575 TI - Cognition in REM sleep behavior disorder - A window into preclinical dementia? PMID- 17869576 TI - Correlates for poor sleepers in a Los Angeles high school. AB - BACKGROUND AND PURPOSE: We explored sleep patterns including morning-evening preference and their associations with other lifestyle determinants among high school students. PARTICIPANTS AND METHODS: We conducted a cross-sectional survey of students grades 9-12 from a private high school in the United States. One hundred and thirty-one students completed an online survey comprising 23 original, investigator-created questions, a mood scale, the Pittsburgh Sleep Quality Index (PSQI), and the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ). RESULTS: We found that 80% of students reported a sleep deficit. As defined by the PSQI, 69% of girls and 58% of boys in this sample were poor sleepers. Eveningness was a strong predictor of poor sleep, particularly among students aged 15 years (odds ratio [OR] 9.92; 95% confidence interval [CI], 1.52 64.8), among whom poor sleep quality was also associated with a higher body mass index (BMI) (OR, 6.97; 95% CI, 1.01-48.2). CONCLUSIONS: Our pilot study suggests that morningness-eveningness is a strong predictor of sleep quality among high school students. PMID- 17869577 TI - The impact of electronic media on mental and somatic children's health. AB - A concise review of the literature on the influence of electronic media on children's health is given. The exposure to different media is estimated with special reference to the situation in Germany. The impact on violence and aggressive behavior, on sexuality, on physical activity, obesity and nutrition, on substance use and abuse and addiction, on anxiety, depression, irregular sleep, and attention deficits, on cognition, language and reading, creativity is discussed. Although some of the results reported are still in question, there is no doubt that television and other electronic media negatively influence children's mental and somatic well-being. They have fundamentally changed the life of children and expose them to a powerful experiment with unpredictable and possibly irreversible outcome. PMID- 17869578 TI - Assessment of a groundwater contamination with vinyl chloride (VC) and precursor volatile organic compounds (VOC) by use of a geographical information system (GIS). AB - Regarding the health effects of volatile organic compounds (VOC) and their decomposition products (particularly vinyl chloride (VC)) under chronic low-dose exposure, VOC groundwater contaminations are seen to be an ongoing public health issue. This article presents results of a long-term investigation surveying VOC and VC groundwater contamination upstream of a large groundwater works in Cologne, Germany. For 10 years a contaminated aquifer has been monitored for different VOC and for VC. In total, 255 samples have been taken to assess both the 3-dimensional distribution and the temporal dynamics of the contaminants. VOC and VC precursor substances have been measured by means of pentane-liquid-liquid extraction, GC and ECD, VC by means of derivatisation to 1,2 dibromochloroethane, GC, ECD, and by purge and trap technique and GC-MS-coupling. For spatial analysis all test results and additional hydrogeological attribute data have been transferred to a GIS. The spatial VOC distribution has been assessed by use of kriging interpolation indicating a decrease of the initial contaminants in time. A cluster analysis allowed to distinguish several independent contaminations within the large contamination area. The VC contamination was increasing. Anaerobic microbial dechlorination of VOC and subsequent VC accumulation were seen to be as credible from several indications (VC presence, downstream change of tetra/trichloroethylene-ratio and anaerobic conditions in the aquifer, high Fe(2+)- and Mn(2+)-concentrations). There was no statistically significant vertical differentiation of VOC and VC concentrations. The VOC load within the different water protection zones of the waterworks could be assessed. PMID- 17869579 TI - Nosocomial infection: a risk factor for a complicated course in children with respiratory syncytial virus infection--results from a prospective multicenter German surveillance study. AB - BACKGROUND: Nosocomially acquired respiratory syncytial virus infections (RSV-NI) may cause serious problems in hospitalized paediatric patients. Hitherto, prospectively collected representative data on RSV-NI from multicenter studies in Germany are limited. METHODS: The DMS RSV Ped database was designed for the prospective multicenter documentation and analysis of clinically relevant aspects of the management of inpatients with RSV-infection. The study covered six consecutive seasons (1999-2005); the surveillance took place in 14 paediatric hospitals in Germany. RESULTS: Of the 1568 prospectively documented RSV infections, 6% (n=90) were NI and 94% (n=1478) were community acquired (CA). A significantly higher proportion in the NI group displayed additional risk factors like prematurity, chronic lung disease, mechanical ventilation (med. history), congenital heart disease, and neuromuscular impairment. Of all NI, 55% occurred in preterms (30.6% of all RSV-infections in preterms with severe chronic lung disease of prematurity were NI). Illness severity as well as the total mortality, but not the attributable mortality was significantly higher in the NI group. In the multivariate analysis, NI was significantly associated with the combined outcome 'complicated course of disease'. CONCLUSION: This is the first prospective multicenter study from Germany, which confirms the increased risk of a severe clinical course in nosocomially acquired RSV-infection. Of great concern is the high rate of (preventable) NI in preterms, in particular in those with severe chronic lung disease or with mechanical ventilation due to other reasons. PMID- 17869581 TI - Indoor and outdoor air pollution: tobacco smoke, moulds and diseases in infants and children. AB - Although outdoor air pollution first brought the issue of air pollution health effects to public attention, it is now indoor air pollution that likely has the greatest impact on children's health. The World Health Organization estimates that the global burden of disease from indoor air pollution is far greater than the burden from outdoor air pollution. This review focuses on two indoor pollutants, one that has been well studied, and another that deserves additional study. There is very strong evidence about the harmful effects of tobacco. Policy to decrease children's tobacco exposure and use should be implemented without delay. The emerging findings linking household inhalation of mould spores and infant pulmonary hemorrhage merit follow-up in other countries, because they may provide clues to some deaths from the sudden infant death syndrome. PMID- 17869580 TI - Health risks of early swimming pool attendance. AB - Swimming pool attendance and exposure to chlorination by-products showed adverse health effects on children. We assessed whether early swimming pool attendance, especially baby swimming, is related to higher rates of early infections and to the development of allergic diseases. In 2003-2005, 2192 children were analysed for the 6-year follow-up of a prospective birth cohort study. Data on early swimming pool attendance, other lifestyle factors and medical history were collected by parental-administered questionnaire. Bivariate and multivariate logistic regression analyses were used to evaluate associations. Babies who did not participate in baby swimming had lower rates of infection in the 1st year of life (i) diarrhoea: OR 0.68 CI 95% 0.54-0.85; (ii) otitis media: OR 0.81 CI 95% 0.62-1.05; (iii) airway infections: OR 0.85 CI 95% 0.67-1.09. No clear association could be found between late or non-swimmers and atopic dermatitis or hay fever until the age of 6 years, while higher rates of asthma were found (OR 2.15 95% CI 1.16-3.99), however, potentially due to reverse causation. The study indicates that, in terms of infections, baby swimming might not be as harmless as commonly thought. Further evidence is needed to make conclusions if the current regulations on chlorine in Germany might not protect swimming pool attendees from an increased risk of gastrointestinal infections. In terms of developing atopic diseases there is no verifiable detrimental effect of early swimming. PMID- 17869582 TI - Improving parenting practices in order to prevent child behavior problems: a study on parent training as part of the EFFEKT program. AB - Inappropriate parenting behavior in the family can be one of many risk factors in children's social development. Accordingly, prevention programs aim at improving parenting. The relation between parenting and problem behavior was investigated and an evaluation reported of parent training in the German prevention program EFFEKT (Entwicklungsforderung in Familien: Eltern- und Kinder-Training - Enhancing the development of families: parent and child training). As part of the Erlangen-Nuremberg Development and Prevention Study [Losel, F., Beelmann, A., Jaursch, S., Koglin, U., Stemmler, M., 2005a. Entwicklung und Pravention fruher Problem des Sozialverhaltens: Die Erlangen-Nurnberger Studie. In: Cierpka, M. (Ed.), Moglichkeiten der Gewaltpravention. Vandenhoeck und Ruprecht, Gottingen, pp. 201-249.], this paper presents data on 128 mothers and 16 fathers who participated in the parent training. The trained parents were compared with a matched control group on scales of self-reported parenting behavior. Significant effects were found 2-3 months after training and in a follow-up survey 1 year later. Trained mothers showed more positive parenting and less inconsistent discipline than control mothers. Results for fathers were not significant. Our results suggest that with the EFFEKT parent training it is possible to change the child's family environment in a positive manner, with relatively low costs for the parents regarding time and money, but with sustainable effects. PMID- 17869583 TI - Continuous medical education (CME): do we need CME for paediatric environmental medicine in Europe? AB - The knowledge about the influence of environmental hazards on children's health is increasing enormously. European Ministers of Health and Environment, like many other stakeholders, identified the environmental hazards in Europe for the health of children as so serious, that they called for a "Children's Environment and Health Action Plan for Europe (CEHAPE)" approved in June 2004. The knowledge of paediatricians and other health care providers on children's health and environment in Europe is insufficient, due to the lack of training in environmental medicine for medical students, clinical trainees and postgraduates. Only continuous medical education in environmental medicine can help to fill this gap of knowledge and is thereby urgently needed. The World Health Organization developed a training package for health care providers for children's health and environment, containing excellent material for paediatric training events. The International Network on Children's Health, Environment and Safety (INCHES) developed additional training material for paediatricians within the Children's Health, Environment and Safety Training (CHEST) project. The German Network Children's Health and Environment offers training for paediatric doctors' assistants in primary prevention. To improve knowledge about children's health and environment at all levels in paediatric settings, greater efforts of national institutions, paediatric associations and other institutions are necessary. It is time to strengthen existing structures and to introduce, where necessary, new structures for training in environmental medicine. PMID- 17869584 TI - Triathlon related musculoskeletal injuries: the status of injury prevention knowledge. AB - Triathlon is a popular participation sport that combines swimming, cycling and running into a single event. A number of studies have investigated the incidence of injury, profile of injuries sustained and factors contributing to triathlon injury. This paper summarises the published literature in the context of the evidence base for the prevention of triathlon related injuries. Relevant articles on triathlon injuries were sourced from peer-reviewed English language journals and assessed using the Translating Research into Injury Prevention Practice (TRIPP) framework. This review highlights the significant knowledge gap that exists in the published literature describing the incidence of injury, the profile of injuries sustained and evidence for the prevention of injury in triathlon. Despite the number of studies undertaken to address TRIPP Stages 1 and 2 (injury surveillance, aetiology and mechanism of injury), most triathlon studies have been limited by retrospective designs with substantial, and unvalidated, recall periods, inconsistency in the definitions used for a reportable injury and exposure to injury, or a failure to capture exposure data at all. Overall, the paucity of quality, prospective studies investigating the incidence of injury in triathlon and factors contributing to their occurrence has led to an inability to adequately inform the development of injury prevention strategies (TRIPP Stages 3-6) for this sport, a situation that must be rectified if gains are to be made in reducing the burden of triathlon related injury. PMID- 17869585 TI - Plasmon-waveguide resonance (PWR) spectroscopy for directly viewing rates of GPCR/G-protein interactions and quantifying affinities. AB - Plasmon-waveguide resonance (PWR) spectroscopy is an optical technique that has been developed in our laboratories and applied to the study of membrane associated proteins, especially GPCRs. It has high sensitivity and requires no labeling of materials, and it can monitor changes in proteolipid mass density and conformation in real time using plasmon excitation by light polarized both perpendicular and parallel to the resonator surface. Direct measurements will be described of the association of ligands and G-proteins to GPCRs incorporated into a self-assembled lipid bilayer deposited on the silica surface of a PWR resonator. These studies have provided new insights into the functioning of this important class of signaling proteins. PMID- 17869586 TI - Electrochemiluminescence to detect surface proteins on live cells. AB - Flow cytometry and cell-based enzyme-linked immunosorbent assays have been used to detect surface proteins on cells. A recently available electrochemiluminescent assay methodology using carbon surface electrodes built into the bottom of microwell plates can be used as an alternative to these methods and has some advantages. The carbon surface plates bind suspension cells tightly enough to allow plates to be washed using a plate washer. This eliminates the centrifugation steps typically used for washing suspension cells. For adherent cells, human umbilical vein endothelial cells can be grown, activated, and assayed in the same carbon surface plate. This eliminates the need to detach cells from tissue culture plates for analysis, making the electrochemiluminescent assay much easier to perform than a corresponding flow cytometry assay. This electrochemiluminescence technology provides a high throughput method to detect surface proteins on live cells. PMID- 17869587 TI - Clinical reasoning and its application to nursing: concepts and research studies. AB - Clinical reasoning may be defined as "the process of applying knowledge and expertise to a clinical situation to develop a solution" [Carr, S., 2004. A framework for understanding clinical reasoning in community nursing. J. Clin. Nursing 13 (7), 850-857]. Several forms of reasoning exist each has its own merits and uses. Reasoning involves the processes of cognition or thinking and metacognition. In nursing, clinical reasoning skills are an expected component of expert and competent practise. Nurse research studies have identified concepts, processes and thinking strategies that might underpin the clinical reasoning used by pre-registration nurses and experienced nurses. Much of the available research on reasoning is based on the use of the think aloud approach. Although this is a useful method, it is dependent on ability to describe and verbalise the reasoning process. More nursing research is needed to explore the clinical reasoning process. Investment in teaching and learning methods is needed to enhance clinical reasoning skills in nurses. PMID- 17869588 TI - Effects of acclimation temperature and cadmium exposure on mitochondrial aconitase and LON protease from a model marine ectotherm, Crassostrea virginica. AB - Temperature and heavy metals such as cadmium (Cd) are important stressors which can strongly affect physiology of marine ectotherms in polluted estuaries. Mitochondria are among the key intracellular targets for these stressors, but the mechanisms of Cd-induced mitochondrial damage are not fully understood. In this study we determined the effects of acclimation temperature (12, 20 and 28 degrees C) and Cd exposure (0 or 50 microg L(-1) Cd) in vivo on activity and mRNA expression of a key mitochondrial enzyme, aconitase, which is known as a sensitive marker of oxidative stress, and on mRNA expression of LON protease involved in the degradation of oxidatively damaged mitochondrial proteins, in eastern oysters Crassostrea virginica. Sensitivity of mitochondrial aconitase to exposure to Cd in vitro (0 or 50 microM) was also determined in oysters acclimated to different temperatures and Cd levels. Acclimation at 28 degrees C resulted in a strong decrease in activity of mitochondrial aconitase as well as mRNA expression of aconitase and LON protease suggesting mitochondrial dysfunction at elevated temperatures. Exposure of isolated mitochondria to 50 microM Cd in vitro resulted in a 20-25% inhibition of mitochondrial aconitase reflecting oxidative damage of this enzyme. However, long-term (3-6 weeks) exposure of whole oysters to Cd had no effect on mitochondrial aconitase activity suggesting that this enzyme is well protected against Cd-induced oxidative stress in vivo. Aconitase mRNA expression was positively correlated with the enzyme activity within control and Cd-exposed groups; however, this correlation was strikingly different when compared between control and Cd-exposed oysters. The level of aconitase transcript was considerably lower (3-13-fold) in Cd-exposed oysters while the specific aconitase activities were similar in control and Cd exposed oysters indicating regulation at the post-transcriptional level. LON protease expression was upregulated by 2-4-fold in Cd-exposed oysters suggesting an increase in mitochondrial protein degradation as a novel protective mechanism against Cd-induced mitochondrial stress. Our data indicate that mitochondrial aconitase is not a good biomarker for Cd-induced oxidative stress in oysters in vivo, because of its complex regulation at transcriptional and post transcriptional levels, low sensitivity to Cd effects in vivo but high sensitivity to acclimation temperature that can potentially mask effects of other stressors under the field conditions. PMID- 17869589 TI - Exercise, oxidative stress and hormesis. AB - Physical inactivity leads to increased incidence of a variety of diseases and it can be regarded as one of the end points of the exercise-associated hormesis curve. On the other hand, regular exercise, with moderate intensity and duration, has a wide range of beneficial effects on the body including the fact that it improves cardio-vascular function, partly by a nitric oxide-mediated adaptation, and may reduce the incidence of Alzheimer's disease by enhanced concentration of neurotrophins and by the modulation of redox homeostasis. Mechanical damage mediated adaptation results in increased muscle mass and increased resistance to stressors. Physical inactivity or strenuous exercise bouts increase the risk of infection, while moderate exercise up-regulates the immune system. Single bouts of exercise increases, and regular exercise decreases the oxidative challenge to the body, whereas excessive exercise and overtraining lead to damaging oxidative stress and thus are an indication of the other end point of the hormetic response. Based upon the genetic setup, regular moderate physical exercise/activity provides systemic beneficial effects, including improved physiological function, decreased incidence of disease and a higher quality of life. PMID- 17869590 TI - Review of ICT-based services for identified unmet needs in people with dementia. AB - Some of the needs that people with dementia and their informal carers currently perceive as insufficiently met by regular care and support services might be alleviated, or even be met, using modern Information and Communication Technology (ICT). The study described in this paper was designed to provide an insight into the state of the art in ICT solutions that could contribute to meet the most frequently mentioned unmet needs by people with dementia and their informal carers. These needs can be summarized as (1) the need for general and personalized information; (2) the need for support with regard to symptoms of dementia; (3) the need for social contact and company; and (4) the need for health monitoring and perceived safety. Databases that were searched include: PubMed, Cinahl, Psychinfo, Google (Scholar), INSPEC and IEEE. In total 22 websites and 46 publications were included that satisfied the following criteria: the article reports on people with dementia and/or their informal carers and discusses an ICT-device that has been tested within the target group and has proven to be helpful. Within the first need area 18 relevant websites and three studies were included; within the second need area 4 websites and 20 publications were included. Within the third and fourth need area 11 and 12 publications were included respectively. Most articles reported on uncontrolled studies. It is concluded that the informational websites offer helpful information for carers but seem less attuned to the person with dementia and do not offer personalized information. ICT solutions aimed at compensating for disabilities, such as memory problems and daily activities demonstrate that people with mild to moderate dementia are capable of handling simple electronic equipment and can benefit from it in terms of more confidence and enhanced positive effect. Instrumental ICT support for coping with behavioral and psychological changes in dementia is relatively disregarded as yet, while support for social contact can be effectively realized through, for example, simplified (mobile) phones or videophones or (entertainment) robots. GPS technology and monitoring systems are proven to result in enhanced feelings of safety and less fear and anxiety. Though these results are promising, more controlled studies in which the developed ICT solutions are tested in real life situations are needed before implementing them in the care for people with dementia. It is recommended that future studies also focus on the integration of the current techniques and solutions. PMID- 17869591 TI - Control of breathing during cortical substitution of the spontaneous automatic respiratory rhythm. AB - This study addresses the following question: does the ventilatory control system adjust total ventilation in accord with the regulatory demands of the physiological dead space ventilation (VD) when the breathing frequency changes, and if so, how? A simple proportionality between the amplitude of the respiratory motor output (VT) and the respiratory period (TTOT) during such changes will not provide for regulation of arterial (PaCO2); the relationship requires a positive intercept of magnitude VD, i.e. VT=VATTOT+VD. We therefore determined the relationship between VT and TTOT when breathing frequency was changed in a ramp like manner (from 6 to 20 cycles/min), in an imperceptible manner, during a paced breathing protocol in which the subjects voluntarily triggered the breath onset, thereby imposing a rhythm different from the one spontaneously generated by the automatic central pattern generators (CPGs). While the resulting breath magnitude was strongly correlated to the breath duration (slope: 6.50+/-2.91 l/min) there was, in all cases, a statistically significant positive intercept on the VT axis (238+/-112 ml) leading to a relationship of the form: VT=VATTOT+VD. Consequently, the ventilatory output changed as a function of the breathing frequency-induced dead space ventilation changes, maintaining end-tidal PCO2 (PETCO2) constant. These results are consistent with a centrally set program for generating regulatory combinations of respiratory cycle durations and magnitudes that "take into account" the f-induced variation of dead space ventilation. This appears not to be dependent on the structures producing the respiratory rhythm (cortex versus central pattern generators). It is suggested that, during volitional control of breathing rhythm, the signal used for adjusting the magnitude to the timing of the ventilatory output is derived from information contained in the duration of preceding expiration. PMID- 17869592 TI - Partitioning of caseinomacropeptide in aqueous two-phase systems. AB - This study evaluates the influence of type of salt and temperature on the partition coefficient of caseinomacropetide (CMP) to determine the best conditions for the recovery of CMP in aqueous two-phase systems (ATPS) composed by poly(ethylene glycol) (PEG) 1500 and an inorganic salt (potassium phosphate, sodium citrate, lithium sulfate or sodium sulfate). In all systems, CMP presented affinity for the PEG-rich phase. The PEG1500+lithium sulfate showed the highest values of partitioning coefficient. In addition, thermodynamic parameters (DeltaH degrees , DeltaS degrees , DeltaG degrees) as a function of temperature, were calculated for the system PEG1500-sodium citrate at different PEG concentrations and the results imply thermodynamic differences between partitioning of CMP in this system. PMID- 17869593 TI - Microfluidic immunoaffinity separations for bioanalysis. AB - Microfluidic devices often rely on antibody-antigen interactions as a means of separating analytes of interest from sample matrices. Immunoassays and immunoaffinity separations performed in miniaturized formats offer selective target isolation with minimal reagent consumption and reduced analysis times. The introduction of biological fluids and other complicated matrices often requires sample pretreatment or system modifications for compatibility with small-scale devices. Miniaturization of external equipment facilitates the potential for portable use such as in patient point-of-care settings. Microfluidic immunoaffinity systems including capillary and chip platforms have been assembled from basic instrument components for fluid control, sample introduction, and detection. The current review focuses on the use of immunoaffinity separations in microfluidic devices with an emphasis on pump-based flow and biological sample analysis. PMID- 17869594 TI - Oligomeric state of lipocalin-1 (LCN1) by multiangle laser light scattering and fluorescence anisotropy decay. AB - Multiangle laser light scattering and fluorescence anisotropy decay measurements clarified the oligomeric states of native and recombinant tear lipocalin (lipocalin-1, TL). Native TL is monomeric. Recombinant TL (5-68 microM) with or without the histidine tag shows less than 7% dimer formation that is not in equilibrium with the monomeric form. Fluorescence anisotropy decay showed a correlation time of 9-10 ns for TL (10 microM-1 mM). Hydrodynamic calculations based on the crystallographic structure of a monomeric TL mutant closely concur with the observed correlation time. The solution properties calculated with HYDROPRO and SOLPRO programs from the available crystallographic structure of a monomeric TL mutant concur closely with the observed fluorescence anisotropy decay. The resulting model shows that protein topology is the major determinant of rotational correlation time and accounts for deviation from the Stokes Einstein relation. The data challenge previous gel filtration studies to show that native TL exists predominantly as a monomer in solution rather than as a dimer. Delipidation of TL results in a formation of a complex oligomeric state (up to 25%). These findings are important as the dynamic processes in the tear film are limited by diffusional, translational as well as rotational, properties of the protein. PMID- 17869595 TI - Mini-laparotomy cholecystectomy: technique, outcomes: a prospective study. AB - BACKGROUND: The last decades have been characterized by a rapid growth in minimally invasive techniques for acute and chronic cholecystitis. The aim of our study was to analyze 10 years of experience with the mini-laparotomy cholecystectomy. METHODS: From 1994 to 2004, we performed 2295 mini-laparotomy cholecystectomies, including 1028 patients with acute and 1267 patients with chronic cholecystitis. There were 1780 women and 515 men. We utilized a special surgical tool kit with a system of circular and small hook-retractors incorporating an illuminator and long surgical instruments. Our surgical approach was carried out using a 3-5 cm longitudinal incision located immediately above the gallbladder with a muscle splitting technique. RESULTS: The mean time of operation was 64.5+/-24.5 min and the conversion rate was 3.7%. Intraoperative complications occurred in 25 cases (1.1%), including 4 cases (0.17%) of biliary tract injury. Cholecystectomy was combined with intervention on the choledochus and the papilla of Vater in 133 patients with choledocholithiasis. Postoperative complications developed in 4.1%. Five hundred and five patients (22%) required opioid analgesics on the first postoperative day. The mortality rate was 0.17%. The mortalities involved patients who had severe concomitant diseases and required urgent surgery for acute cholecystitis. Patients operated for acute cholecystitis had significantly higher rates of postoperative complications (5.8% vs. 2.8%), need for opioids (25.5% vs. 19.2%) and mortality (0.39% vs. 0%). CONCLUSIONS: Mini-laparotomy cholecystectomy is an alternative to laparoscopic approach in the surgical treatment of acute and chronic cholecystitis. PMID- 17869596 TI - The efficacy of local anaesthetic for pain after iliac bone harvesting: a randomised controlled trial. AB - INTRODUCTION: Autogenous bone grafting is commonly used in reconstructive surgery but postoperative pain from the donor site can be severe, delaying early mobilisation and preventing discharge from hospital. METHOD: An RCT of levobupivacaine infusion (16.25mg/h for 24h) of iliac crest wounds versus placebo. Postoperative pain was recorded immediately on returning to the ward, then at 1, 2, 3, 4, 5, 6h, morning and evening on subsequent days until discharge, and at the 7-day clinic appointment. Mobility was recorded twice daily and at 7days. RESULTS: Of 46 evaluable patients, 25 were randomised to levobupivacaine and 21 to placebo. Mean pain scores for (i) average pain from initial assessment to 6h; (ii) 1day in the morning; (iii) 1day in the evening; (iv) at 2days; and (v) follow-up were all statistically significant in favour of lower pain scores in the levobupivicaine group (p-values all <0.01). Comparison between the study groups for mobility found 6 patients unable to get out of bed in the placebo group and none in the local anaesthetic group at the initial assessment (Fisher's exact test p-value=0.005), and 2 patients at 24h. Patients in the local anaesthetic group were always more mobile and this was statistically significant even at 7days for gait disturbance, limp, deviation of gait and unequalness of stride. There were no complications relating to the infusion system. CONCLUSIONS: Local anaesthetic significantly reduced postoperative pain and improved mobility. We recommend that surgeons use a local anaesthetic infusion to improve the postoperative experience for their patients undergoing iliac crest grafting. PMID- 17869597 TI - Splenic artery aneurysms in pregnancy--a systematic review. AB - Visceral artery aneurysm is an uncommon pathology, with a potential for rupture. Splenic artery aneurysms (SAA) are most commonly (60%) associated with a high mortality rate of 25% in case of aneurysm rupture. This increases disproportionately to 75% among pregnant women with fetal mortality of 95%. Although this is a rare event, because of the associated catastrophic consequences, prompt management of splenic artery aneurysms (SAA) is of prime importance. This systematic review provides up-to-date information about the management of splenic artery aneurysms in pregnancy. PMID- 17869598 TI - Comparison of topical glyceryl trinitrate with lignocaine ointment for treatment of anal fissure: a randomised controlled trial. AB - INTRODUCTION: Topical glyceryl trinitrate (GTN) has gained popularity as a treatment for anal fissure in the West. In our country, lignocaine is still the current treatment for the entity. This study was done to compare the effect of GTN with lignocaine in terms of healing rate and recurrence in South Asian population. METHODS: A prospective, double blinded, randomised controlled trial was conducted on 50 patients (both treatment arms included) of all ages and either gender with a clinical diagnosis of anal fissure. Group A was given 0.2% GTN ointment and Group B was given lignocaine ointment. Both subjective and objective signs of healing were assessed and adverse effects of the treatment were sought. RESULTS: Symptomatic relief was earlier with GTN as compared with lignocaine. Pain relief was steady and sustained in those treated with GTN but returned to pre-treatment status within 5 weeks in patients with lignocaine. After 8 weeks of treatment, 80% of patients in Group A showed clinical signs of healing compared to 32% in Group B (p=0.001). Headache was the main side effect of GTN. At 6-month follow-up, recurrence was seen in 3/8 patients in Group B compared to 8/20 in the GTN Group (p=1). CONCLUSION: Topical GTN has earlier and a higher rate of clinical healing of anal fissure with acceptable side effects. The recurrence rate is high and comparable to lignocaine ointment. It is a safe and an effective treatment of anal fissure in a South Asian population. PMID- 17869599 TI - Frequent low-dose bisphosphonate therapy. PMID- 17869600 TI - Anaerobic biodegradation of methyl tert-butyl ether (MTBE) and related fuel oxygenates. PMID- 17869601 TI - Controlled biomineralization by and applications of magnetotactic bacteria. PMID- 17869602 TI - The distribution and diversity of Euryarchaeota in termite guts. PMID- 17869603 TI - Understanding microbially active biogeochemical environments. PMID- 17869604 TI - The scale-up of microbial batch and fed-batch fermentation processes. PMID- 17869605 TI - Production of recombinant proteins in Bacillus subtilis. PMID- 17869607 TI - Rhizobacteria and plant sulfur supply. PMID- 17869606 TI - Quorum sensing: fact, fiction, and everything in between. PMID- 17869608 TI - Antibiotics and resistance genes: influencing the microbial ecosystem in the gut. PMID- 17869609 TI - Fate decisions regulating bone marrow and peripheral B lymphocyte development. AB - In adult mammals, bone marrow pluripotent hematopoietic stem cells generate B lymphoid-specified progeny that progress through a series of well-characterized stages before generating B-cell receptor expressing B lymphocytes. These functionally immature B lymphocytes then migrate to the spleen wherein they differentiate through transitional stages into follicular or marginal zone B lymphocytes capable of responding to T-dependent and -independent antigens, respectively. During the terminal stages of B lymphocyte development in the bone marrow, as well as immediately following egress into the peripheral compartments, B lymphocytes are counterselected to eliminate B lymphocytes with potentially dangerous self-reactivity. These developmental and selection events in the bone marrow and periphery are dependent on the integration of intrinsic genetic programs with extrinsic microenvironmental signals that drive progenitors toward increasing B lineage commitment and maturation. This chapter provides a comprehensive overview of the various stages of primary and secondary B lymphocyte development with an emphasis on the selection processes that affect decisions at critical checkpoints. Our intent is to stress the concept that at many steps in the developmental process leading to a mature immunocompetent B lymphocyte, B lineage cells are integrating multiple and different signaling inputs that are translated into specific and appropriate cell fate decisions. PMID- 17869611 TI - B-cell self-tolerance in humans. AB - Two mechanisms account for generation of the human antibody repertoire; V(D)J recombination during the early stages of B-cell development in the bone marrow and somatic mutation of immunoglobulin genes in mature B cells responding to antigen in the periphery. V(D)J recombination produces diversity by random joining of gene segments and somatic mutation by introducing random point mutations. Both are required to attain the degree of antigen receptor diversification that is necessary for immune protection: defects in either mechanism are associated with increased susceptibility to infection. However, the downside of producing enormous random diversity in the antibody repertoire is the generation of autoantibodies. To prevent autoimmunity B cells expressing autoantibodies are regulated by strict mechanisms that either modify the specificity of autoantibodies or the fate of cells expressing such antibodies. Abnormalities in B-cell self-tolerance are associated with a large number of autoimmune diseases, but the precise nature of the defects is less well defined. Here we summarize recent data on the self-reactive B-cell repertoire in healthy humans and in patients with autoimmunity. PMID- 17869610 TI - Tolerance and autoimmunity: lessons at the bedside of primary immunodeficiencies. AB - The recent progress in the genetic characterization of many primary immunodeficiencies (PIDs) allows for a better understanding of immune molecular and cellular mechanisms. The present chapter discusses associations between PIDs and autoimmune diseases (AIDs) in this new light. PIDs are classified according to the frequency of association with AIDs, defining four groups of conditions: systematic (more than 80% of all patients), strong (10-80%), mild (less than 10%), and absent (no available descriptions). Several general conclusions could be drawn: (1) pathological autoimmune (AI) manifestations are very frequently associated with PIDs, indicating that, contrary to conventional notions, antimicrobial protection and natural tolerance to body tissues share many basic mechanisms; (2) in some gene defects, association is so strong that one could speak of "monogenic" AIDs; (3) basic types of PIDs are selectively associated with AID of a particular set of target tissues; (4) while for some gene defects, current theory satisfactorily explains pathogenesis of the corresponding AID, other situations suggest extensive gaps in the present understanding of natural tolerance; and (5) not exceptionally, observations on the AI phenotype for the same gene defect in mouse and man are not concordant, perhaps owing to the limited genetic diversity of mouse models, often limited to a single mouse strain. Overall, clinical observations on PID support the new paradigm of "dominant" tolerance to self-components, in which AID owes to deficits in immune responses (i.e., in regulatory mechanisms), rather than from excessive reactivity. PMID- 17869612 TI - Manipulation of regulatory T-cell number and function with CD28-specific monoclonal antibodies. AB - Suppressor or "regulatory" CD4 T cells play a key role in the control of autoimmunity and overshooting immune responses to foreign antigens, but can also obstruct effective anticancer therapies. The homeostasis and activation of these regulatory T cells (Treg cells) is tightly connected to that of effector CD4 T cells via the costimulatory receptor CD28 and the cytokine IL-2: Both subsets require costimulation to be activated by antigen, and Treg cells additionally depend on IL-2 produced by effector CD4 T cells in a costimulation-dependent fashion. Depending on the therapeutic aim, blockade, or stimulation of CD28 with monoclonal antibodies (mAb) can therefore profoundly affect the size and activity of the Treg compartment. In this chapter, experiments performed in rodents with distinct types of CD28-specific mAb, and the recent failure to translate CD28 driven Treg activation into humans, are discussed. PMID- 17869613 TI - Osteoimmunology: a view from the bone. AB - Osteoimmunology can be defined in a very broad sense as the field of research focusing on interrelations between bone and the immune system. This is a rather opened field that covers at least three different issues. The first one is developmental, that is, organogenesis of the bones and immune systems. The second is post-developmental, that is, the role of the bone in the regulation of the immune response and role of the immune cells on the regulation of bone homeostasis. The third one is related to pathologies: Can immune cells be involved in the development of bone-related pathology? Can deregulation of the bone be causing immune-related diseases? I will not review in detail the bibliography covering osteoimmunology. This has been extensively done in Immunological Reviews (Vol. 208, December 2005) and Current Opinion in Rheumatology (Vol. 18, 2006). I will rather critically comment on hypotheses and concepts in osteoimmunology from a bone biologist's point of view. PMID- 17869614 TI - Mast cell proteases. AB - Mast cells (MCs) are traditionally thought of as a nuisance for its host, for example, by causing many of the symptoms associated with allergic reactions. In addition, recent research has put focus on MCs for displaying harmful effects during various autoimmune disorders. On the other hand, MCs can also be beneficial for its host, for example, by contributing to the defense against insults such as bacteria, parasites, and snake venom toxins. When the MC is challenged by an external stimulus, it may respond by degranulation. In this process, a number of powerful preformed inflammatory "mediators" are released, including cytokines, histamine, serglycin proteoglycans, and several MC-specific proteases: chymases, tryptases, and carboxypeptidase A. Although the exact effector mechanism(s) by which MCs carry out their either beneficial or harmful effects in vivo are in large parts unknown, it is reasonable to assume that these mediators may contribute in profound ways. Among the various MC mediators, the exact biological function of the MC proteases has for a long time been relatively obscure. However, recent progress involving successful genetic targeting of several MC protease genes has generated powerful tools, which will enable us to unravel the role of the MC proteases both in normal physiology as well as in pathological settings. This chapter summarizes the current knowledge of the biology of the MC proteases. PMID- 17869615 TI - Animal-human hybrid-embryo research. PMID- 17869616 TI - Aboriginal health: a decade-old election promise. PMID- 17869617 TI - Doctors and medical statistics. PMID- 17869618 TI - Primary health care comes of age. Looking forward to the 30th anniversary of Alma Ata: call for papers. PMID- 17869619 TI - Drug-eluting stents and late stent thrombosis. PMID- 17869620 TI - Trials of venous thromboembolism prevention. PMID- 17869621 TI - Do not forget culture when studying mental health. PMID- 17869622 TI - Andy Haines: exploring the effects of global environmental change and energy use on health. PMID- 17869624 TI - The VALIDD study. PMID- 17869625 TI - The VALIDD study. PMID- 17869627 TI - Ovarian cancer and hormone replacement therapy. PMID- 17869629 TI - Quality-of-life assessment in trials of lung cancer. PMID- 17869630 TI - Radioiodine and flame sensors. PMID- 17869631 TI - Hepatitis E associated with surgical training on pigs. PMID- 17869632 TI - Politics of health systems: WHO's new frontier. PMID- 17869633 TI - Motor traffic and the pollution of the air: 100 years on. PMID- 17869634 TI - Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis. AB - BACKGROUND: Whether the two drug-eluting stents approved by the US Food and Drug Administration-a sirolimus-eluting stent and a paclitaxel-eluting stent-are associated with increased risks of death, myocardial infarction, or stent thrombosis compared with bare-metal stents is uncertain. Our aim was to compare the safety and effectiveness of these stents. METHODS: We searched relevant sources from inception to March, 2007, and contacted investigators and manufacturers to identify randomised controlled trials in patients with coronary artery disease that compared drug-eluting with bare-metal stents, or that compared sirolimus-eluting stents head-to-head with paclitaxel-eluting stents. Safety outcomes included mortality, myocardial infarction, and definite stent thrombosis; the effectiveness outcome was target lesion revascularisation. We included 38 trials (18,023 patients) with a follow-up of up to 4 years. Trialists and manufacturers provided additional data on clinical outcomes for 29 trials. We did a network meta-analysis with a mixed-treatment comparison method to combine direct within-trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. FINDINGS: Mortality was similar in the three groups: hazard ratios (HR) were 1.00 (95% credibility interval 0.82-1.25) for sirolimus-eluting versus bare-metal stents, 1.03 (0.84-1.22) for paclitaxel eluting versus bare-metal stents, and 0.96 (0.83-1.24) for sirolimus-eluting versus paclitaxel-eluting stents. Sirolimus-eluting stents were associated with the lowest risk of myocardial infarction (HR 0.81, 95% credibility interval 0.66 0.97, p=0.030 vs bare-metal stents; 0.83, 0.71-1.00, p=0.045 vs paclitaxel eluting stents). There were no significant differences in the risk of definite stent thrombosis (0 days to 4 years). However, the risk of late definite stent thrombosis (>30 days) was increased with paclitaxel-eluting stents (HR 2.11, 95% credibility interval 1.19-4.23, p=0.017 vs bare-metal stents; 1.85, 1.02-3.85, p=0.041 vs sirolimus-eluting stents). The reduction in target lesion revascularisation seen with drug-eluting stents compared with bare-metal stents was more pronounced with sirolimus-eluting stents than with paclitaxel-eluting stents (0.70, 0.56-0.84; p=0.0021). INTERPRETATION: The risks of mortality associated with drug-eluting and bare-metal stents are similar. Sirolimus-eluting stents seem to be clinically better than bare-metal and paclitaxel-eluting stents. PMID- 17869635 TI - Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. AB - BACKGROUND: After hip replacement surgery, prophylaxis following discharge from hospital is recommended to reduce the risk of venous thromboembolism. Our aim was to assess the oral, direct thrombin inhibitor dabigatran etexilate for such prophylaxis. METHODS: In this double-blind study, we randomised 3494 patients undergoing total hip replacement to treatment for 28-35 days with dabigatran etexilate 220 mg (n=1157) or 150 mg (1174) once daily, starting with a half-dose 1-4 h after surgery, or subcutaneous enoxaparin 40 mg once daily (1162), starting the evening before surgery. The primary efficacy outcome was the composite of total venous thromboembolism (venographic or symptomatic) and death from all causes during treatment. On the basis of the absolute difference in rates of venous thromboembolism with enoxaparin versus placebo, the non-inferiority margin for the difference in rates of thromboembolism was defined as 7.7%. Efficacy analyses were done by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00168818. FINDINGS: Median treatment duration was 33 days. 880 patients in the dabigatran etexilate 220 mg group, 874 in the dabigatran etexilate 150 mg group, and 897 in the enoxaparin group were available for the primary efficacy outcome analysis; the main reasons for exclusion in all three groups were the lack of adequate venographic data. The primary efficacy outcome occurred in 60 (6.7%) of 897 individuals in the enoxaparin group versus 53 (6.0%) of 880 patients in the dabigatran etexilate 220 mg group (absolute difference -0.7%, 95% CI -2.9 to 1.6%) and 75 (8.6%) of 874 people in the 150 mg group (1.9%, -0.6 to 4.4%). Both doses were thus non-inferior to enoxaparin. There was no significant difference in major bleeding rates with either dose of dabigatran etexilate compared with enoxaparin (p=0.44 for 220 mg, p=0.60 for 150 mg). The frequency of increases in liver enzyme concentrations and of acute coronary events during the study did not differ significantly between the groups. INTERPRETATION: Oral dabigatran etexilate was as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery, with a similar safety profile. PMID- 17869636 TI - Epidemiology of major depressive disorder in elderly Nigerians in the Ibadan Study of Ageing: a community-based survey. AB - BACKGROUND: The growing populations of elderly people in sub-Saharan Africa are exposed to social changes with potential adverse effects on mental health. Our aim was to estimate the occurrence and effect of major depressive disorder in a large and representative community sample of elderly Africans. METHODS: Face-to face interviews with a representative sample of people aged 65 years and older (n=2152) were obtained by a multistage stratified sampling of households in the Yoruba-speaking areas of Nigeria (about 22% of the national population). Major depressive disorder was assessed with the WHO composite international diagnostic interview and diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. FINDINGS: Lifetime and 12-month prevalence estimates of major depressive disorder were 26.2% (95% CI 24.3-28.2) and 7.1% (5.9-8.3) respectively. Female sex (odds ratio [OR] 1.9) and increasing levels of urbanisation of residence (OR 1.4) were associated with this disorder. People with major depressive disorder had impaired quality of life and functioning in home, work, and social roles. Independent ratings of symptom severity confirmed the presence of clinically significant depression in 96.9% of those with diagnosis, and increasing symptom severity was associated with greater disability and poorer quality of life. Only about 37% of lifetime cases had received any treatment, and there was a mean delay of 5 years from onset of depression to receipt of first treatment. Low economic status (0.3) and rural residence (1.0) predicted no treatment. INTERPRETATION: Major depressive disorder is common in elderly Nigerians and its occurrence is related to urbanisation. This disorder is a seriously disabling illness in this group but only a few sufferers have ever received treatment. Health-care services need to invest in effective treatment programmes for major depressive disorder. PMID- 17869637 TI - Diabetes and a large liver. PMID- 17869638 TI - Vasoactive intestinal peptide inhibits liver pathology in acute murine schistosomiasis mansoni and modulates IL-10, IL-12 and TNF-alpha production. AB - Vasoactive intestinal peptide (VIP) exerts a broad range of biologic actions that may include modulation of hepatic granuloma formation. This study aimed to investigate the effect of VIP administration on the course of acute murine schistosomiasis mansoni. Mice were infected each with 40 Schistosoma (S.) mansoni cercariae and injected intraperitoneally with VIP at a total dose of 1mug/kg body weight. VIP treatment was very effective in diminishing worm fecundity, hepatic granuloma size and number by about 54%, 75% and 51%, respectively, and reducing liver collagen content. Serum level of interleukin (IL)-10 was increased, while level of IL-12 and tumor necrosis factor (TNF)-alpha were decreased as a result of VIP administration. Carbohydrate antigen 19.9 (CA 19.9) induced by S. mansoni infection was decreased with VIP treatment. Activities of hepatic gamma-glutamyl transferase (gamma-GT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in liver tissue homogenate of infected treated mice were increased. These results indicate that suitable administration of exogenous VIP can be effective in ameliorating immunopathologic damage associated with schistosomiasis. PMID- 17869639 TI - Stress-induced alterations in the programmed natural cycles of post-natal lymphoid organ development in C57BL/6 mice: Evidence for a regulatory feedback relationship between bone marrow and thymus. AB - This study investigated some effects of weaning and immobilization stress in C57BL/6 mice aged 22-68 days, i.e., over a period including activation of the hypothalamus-pituitary-adrenal (HPA) axis and puberty. Specifically, the study evaluated the evolution, over the referred age interval, of a set of variables (body, thymus, spleen and axillary lymph nodes weights, the proportion of lymphoid cells in the bone marrow, the relative chemoattraction capacity of thymic supernatants for lymphoid cells and the migratory capacity of bone marrow lymphoid cells) in either weaned mice or weaned mice subjected to immobilization stress, compared to "non-stressed" unweaned mice. Cyclic patterns, observed for most variables in unweaned mice, were especially pronounced in two cases: the relative migratory capacity of bone marrow lymphoid cells collected at different ages towards neonatal thymic supernatant, and the relative chemoattraction capacity of thymic supernatants of different ages as tested against a sample of bone marrow lymphoid cells from mice aged 35 days. Weaning stress tended to intensify the involution stages of the cycles in thymus, spleen and lymph node weight, but increased the relative proportion of lymphoid cells in the bone marrow cell population. Both types of exogenous stress tended to affect cycle phase, i.e., cycle peaks and troughs were shifted in time. Correlations were observed between patterns seen in the thymus and bone marrow, suggesting the existence of an autoregulatory feedback loop governing pre-T cell migration and bone marrow/thymus homeostasis. These results also suggest that exogenous stress acts as a non-programmed regulator, modulating the naturally programmed cyclic patterns. PMID- 17869641 TI - B cell activating factor (BAFF) gene promoter activity depends upon co-activator, p300. AB - B-cell activating factor (BAFF) plays a critical role for mature B cell generation and maintenance. We have previously described that mouse BAFF (mBAFF) transcript expression was increased by toll-like receptor 4 (TLR4) agonist, lipopolysaccharide (LPS), through reactive oxygen species (ROS) production and NF kappaB activation. Here, we investigated whether mBAFF expression could be regulated by promoter activation through the cooperation of NF-kappaB and p300, co-activator to various transcription factors. We cloned mBAFF promoter into luciferase-expressing pGL3-basic vector and computer-analyzed its NF-kappaB binding motif. Due to the existence of NF-kappaB binding motifs, activity in 2.0 kb mBAFF promoter was higher than that in 1.0 or 0.5 kb mBAFF promoter. When Raw 264.7 murine macrophages were stimulated with LPS, 2.0 kb mBAFF promoter activity was increased time dependently. Serum deprivation (0.5% FBS) producing ROS and exogenous H(2)O(2) treatment also enhanced mBAFF promoter activity, which was reduced by N-acetyl-l-cysteine (NAC), a well-known ROS scavenger. LPS and serum starved ROS production increased NF-kappaB activation. mBAFF promoter activity was augmented by co-transfection with p65 and/or co-activator, p300. It was inhibited by dominant negative (DN) p300. Binding of p300 to BAFF promoter was detected by chromatin immunoprecipitation (ChIP) assay. Data suggest that mBAFF expression could be regulated by promoter activation through NF-kappaB activation, which might be dependent on the cooperation with co-activator, p300. PMID- 17869640 TI - Loss of Bim results in abnormal accumulation of mature CD4-CD8-CD44-CD25- thymocytes. AB - The process of thymopoiesis is tightly regulated by a series of selection events which ensure that only functional T-lymphocytes directed against foreign antigens are exported into the periphery. The adaptive immune response largely depends on the regulation of thymocyte development, and thymocytes which fail selection in the thymus are removed by apoptosis. However, the roles of specific apoptotic proteins in early T-lymphocyte development are poorly understood. Here, we report a novel function for Bim in thymocyte development. There is an accumulation of thymocytes in Bim(-/-) mice that lack expression of CD4, CD8, CD44, and CD25 but express CD3 and TCRbeta. Further, the CD4(-)CD8(-)CD25(-)CD44(-)CD3(+)TCRbeta(+) thymocytes are smaller and do not proliferate. These data suggest that these thymocytes are mature DN thymocytes that may have down-regulated the expression of CD4 and CD8. The DN thymocyte phenotype in Bim(-/-) mice is unaffected by the additional loss of Bak or Bax and is similar to the thymic phenotype in mice lacking both Bak and Bax. These data demonstrate that Bim functions to ensure the proper homeostasis of mature thymocytes during selection and thymic export. PMID- 17869642 TI - Anti-inflammatory and anti-allergic effects of kefir in a mouse asthma model. AB - Kefir is a microbial symbiont mixture that produces jelly-like grains. As a widely used neutraceutical, however, the therapeutic applicability of kefir is not certain. In order to investigate the pharmacological effects of kefir, we used a mouse asthma model, in which airway inflammation and airway remodeling was produced by ovalbumin sensitization and challenge. BALB/c mice sensitized and challenged to ovalbumin, were treated with kefir (50mg/kg administered by intra gastric mode) 1h before the ovalbumin challenge. Kefir significantly suppressed ovalbumin-induced airway hyper-responsiveness (AHR) to inhaled methacholine. Intra-gastric administration of kefir significantly inhibited the increase in the total inflammatory cell count induced by ovalbumin, and the eosinophil count in bronchoalveolar lavage fluid (BALF). Type 2 helper T cell (Th2) cytokines, such as interleukin-4 and interleukin-13, and total immunoglobulin E (Ig E) levels, were also reduced to normal levels in bronchoalveolar lavage fluid. Histological studies demonstrate that kefir substantially inhibited ovalbumin-induced eosinophilia in lung tissue and mucus hyper-secretion by goblet cells in the airway. Kefir displayed anti-inflammatory and anti-allergic effects in a mouse asthma model and may possess new therapeutic potential for the treatment of allergic bronchial asthma. PMID- 17869643 TI - The Fusarium toxin deoxynivalenol disrupts phenotype and function of monocyte derived dendritic cells in vivo and in vitro. AB - The trichothecene mycotoxin deoxynivalenol (DON) causes systemic immuno suppression in pigs and possibly also in humans after chronic dietary exposure. Since the outcome of every immune response is largely controlled by dendritic cells (DC), we hypothesised that a direct influence of DON on DC function might play a role in mediating DON immunotoxicity. To test this hypothesis, a 2x2 factorial design study was performed. Pigs were fed a control diet or a diet containing DON (DON-diet); monocyte-derived DC (MoDC) from these pigs were then treated with DON in vitro or left untreated. Phenotype and function of the MoDC were analysed. In vitro DON-treatment of MoDC from pigs fed the control diet resulted in a down-regulation of CD80/86 and CD40. This was associated with an activation of the mitogen-associated protein kinases ERK1/2 and JNK. The endocytic activity of MoDC was decreased after in vitro DON-exposure while their T cell stimulatory capacity was not altered. MoDC derived from pigs that had been fed the DON-diet failed to up-regulate MHC-II in response to LPS/TNFalpha. Dietary exposure of pigs to DON inhibited endocytosis of FITC-dextran by MoDC, but did not influence T cell stimulatory capacity. ERK1/2 and JNK were constitutively activated in MoDC from pigs fed the DON-diet. If MoDC derived from pigs fed the DON-diet were exposed to DON in vitro, this resulted in an up regulation of MHC-II and CD80/86, but not CD40. In comparison to untreated MoDC from pigs fed DON-diet, endocytic capacity was further down-regulated, whereas mitogen-activated protein kinase activation was increased. In summary, DON disrupts porcine DC function in vitro and in vivo, which might contribute to the immunosuppressive effects of this mycotoxin. PMID- 17869644 TI - Effects of native and heat-denatured Abrus agglutinin on tumor-associated macrophages in Dalton's lymphoma mice. AB - Tumor-associated macrophages (TAMs) have a complex and ambivalent relationship with tumor progression and elimination. Though TAMs are reported to have pro- and anti-tumor roles, upon modification and activation TAMs can develop tumoricidal activities and thus might have applications in cancer therapy. Various immunomodulatory compounds could be used to modulate TAMs. In this study we used Abrus agglutinin, a plant lectin, in its native and heat-denatured forms, to investigate its effect on TAMs in Dalton's lymphoma-bearing mice. We found that treatment with both native (NA) and heat-denatured agglutinin (HDA) activated the TAMs, which showed significantly increased in vitro cytotoxicity towards tumor cells and production of nitric oxide but no difference in TNF-alpha production. The tumoricidal activities of both NA and HDA were dependent upon the activation of TAMs as in macrophage-depleted Dalton's lymphoma-bearing mice NA and HDA treatment could not decrease the number of tumor cells significantly. Thus, NA and HDA could be used as modulators of TAMs, for their therapeutic use in cancer. PMID- 17869646 TI - Interleukin-10 enhances the CD14-dependent phagocytosis of bacteria and apoptotic cells by human monocytes. AB - Monocytes are centrally involved in both specific and nonspecific immunity by secretion of regulatory immune mediators, phagocytosis, and presentation of antigens. Recent work has shown that monocytes can phagocytose bacteria independently from Fc gamma, complement, and scavenger receptors via a CD14 mediated process. Furthermore, incorporation of cells undergoing apoptosis is also mediated by CD14. In this study we investigated the regulation of monocytic CD14-dependent phagocytosis by the immunoregulatory cytokines interleukin-10 (IL 10), interferon-gamma (IFN-gamma) and transforming growth factor-beta1 (TGF beta1). In this study an in vitro human whole-blood assay was used to test regulation of CD14-dependent phagocytosis of fluorescence-labeled E. coli by IL 10, IFN-gamma, and TGF-beta1 in monocytes from healthy donors. Phagocytosis by monocytes from a patient with paroxysmal nocturnal hemoglobinuria (PNH) and its regulation by IL-10 was also investigated. Finally, regulation of monocytic incorporation of apoptotic Jurkat cells by IL-10 was analyzed. For the CD14 blockade, murine anti-CD14 IgG2a antibody RMO52 was used. We observed that IL-10, suggested to be a monocyte-deactivating cytokine, strongly increased the monocytic CD14-dependent phagocytosis of E. coli. In contrast, IFN-gamma and TGF beta1 depressed monocytic CD14 incorporation of E. coli. Compatible with this, IL 10 upregulated CD14 expression on monocytes, whereas IFN-gamma and TGF-beta1 downregulated its expression. IL-10 also increased the monocytic CD14-dependent and -independent phagocytosis of apoptotic cells. As expected, IL-10 strongly increased the CD14-independent phagocytosis but had no influence on the CD14 dependent phagocytosis of monocytes from a PNH patient. In conclusion, our data support a general role of IL-10 for activating monocytic scavenger functions, which are at least partly mediated by CD14. This is in line with the fact that IL 10 promotes the development of monocytes to macrophages. The contrasting effects of IL-10 and IFN-gamma on monocytic CD14-dependent phagocytosis may reflect a further mechanism counterbalancing antigen-presentation and nonimmunogenic scavenging of bacterial and cellular debris. TGF-beta, however, may be an inhibitor of both systems. PMID- 17869645 TI - Inhibition of NF-kappa B during human dendritic cell differentiation generates anergy and regulatory T-cell activity for one but not two human leukocyte antigen DR mismatches. AB - We examined the in vitro inhibition of human monocyte-derived dendritic cells (DC) maturation via NF-kappaB blockade on T-cell allostimulation, cytokine production, and regulatory T-cell generation. DC were generated from CD14+ monocytes isolated from peripheral blood using GM-CSF and IL-4 for differentiation and TNF-alpha, IL-1beta, and PGE2 as maturational stimuli with or without the NF-kappaB inhibitors, BAY 11-7082 (BAY-DC) or Aspirin (ASA-DC). Stimulator and responder cells were one versus two HLA-DR mismatched in direct versus indirect presentation assays. Both BAY-DC and ASA-DC expressed high levels of HLA-DR and CD86 but always expressed less CD40 compared with controls. Some experiments showed slightly lower levels of CD80. Both BAY- and ASA-allogeneic DC and autologous alloantigen pulsed DC were weaker stimulators of T cells (by MLR) compared with controls, and there was reduced IL-2 and IFN-gamma production by T cells stimulated with BAY-DC or ASA-DC (by ELISPOT) (more marked results were always observed with ASA-treated DC). In addition, NF-kappaB blockade of DC maturation caused the generation of T cells with regulatory function (T regs) but only when T cells were stimulated by either allogeneic (direct presentation) or alloantigen pulsed autologous DC (indirect presentation) with one HLA-DR mismatch and not with two HLA-DR mismatches (either direct or indirect presentation). However, the T regs generated from these ASA-DC showed similar FoxP3 mRNA expression to those from nontreated DC. Extension of this study to human organ transplantation suggests potential therapies using one DR-matched NF-kappaB blocked DC to help generate clinical tolerance. PMID- 17869647 TI - Mannose binding lectin gene polymorphisms are associated with type 1 diabetes in Brazilian children and adolescents. AB - Mannose-binding lectin is an important constituent of the innate immune system, the serum levels of which are greatly affected by polymorphisms of the MBL2 gene: three polymorphisms in exon 1, as well as nucleotide variations in the promoter region of the gene, have been associated with protein deficiency and some infectious and autoimmune disease. The aim of this study was to investigate a possible association between MBL2 gene polymorphisms in patients who have developed type 1 diabetes during childhood and adolescence. We evaluated MBL2 gene polymorphisms in 214 children and adolescents with type 1 diabetes and compared them with a healthy control group, finding significant differences in genotypic and allelic frequencies (p = 0.004 and p = 0.0008, respectively). Our results suggest that patients with type 1 diabetes possessing the 0 allele have a higher risk for developing type 1 diabetes during childhood and adolescence, and that this risk factor is not related to age at diagnosis. PMID- 17869648 TI - Macrophage migration inhibitory factor gene: influence on rheumatoid arthritis susceptibility. AB - The macrophage inhibitory factor (MIF) is a cytokine that has been implicated in several inflammatory and autoimmune diseases, including rheumatoid arthritis, systemic lupus, glomerulonephritis, and multiple sclerosis. In rheumatoid arthritis (RA), results ranging from lack of association of MIF polymorphisms with RA, to involvement in either severity or susceptibility to the disease have been reported in the past. We aimed at investigating the role of this gene in RA in the Spanish population. Two well-known MIF promoter polymorphisms were tested in 606 adult RA patients and 886 healthy controls: a single nucleotide polymorphism at -173G/C and a tetranucleotide repeat (CATT)(5-8) located at -794. We found a significant association of the allele -173C with RA (p = 0.01; odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.06-1.62). The -173C risk allele, previously reported to be transmitted in excess in patients with juvenile idiopathic arthritis, was significantly more frequent in early-onset adult RA patients than in healthy controls (p = 0.003; OR = 1.57; 95% CI = 1.14-2.15), whereas late-onset patients were not significantly different to controls (p = 0.6; OR = 1.09; 95% CI = 0.77-1.55). In conclusion, the -173C allele in the MIF promoter region is associated with increased RA predisposition, mainly in early onset patients. PMID- 17869649 TI - Polymorphisms in the cathepsin L2 (CTSL2) gene show association with type 1 diabetes and early-onset myasthenia gravis. AB - Type 1 diabetes (T1D) is an autoimmune disease characterized by loss of beta cells in the pancreas. The CTSL2 gene encodes the cysteine protease cathepsin V involved in antigen presentation in human cortical thymic epithelial cells, and involvement of the protease in autoimmunity has been suggested. This study aimed to evaluate CTSL2 as a candidate gene for T1D, and test whether the gene predisposes more generally to autoimmune diseases. Four polymorphisms aiming at tagging the CTSL2 locus were genotyped in 421 T1D families, and subsequently in 861 rheumatoid arthritis patients, 530 juvenile idiopathic arthritis patients, and 559 controls of Norwegian origin. Additionally, DNA from 83 German myasthenia gravis (MG) patients and 244 controls were investigated. A polymorphism, rs16919034, situated downstream of CTSL2 was associated with T1D (60.8%T, p = 0.008; p(c) = 0.03). An association with early-onset MG (45% in cases vs 36.6% in controls; p = 0.03) was observed for another polymorphism (rs4361859) situated upstream of the gene, but within the same linkage disequilibrium block. No association was observed in rheumatoid arthritis or juvenile idiopathic arthritis. Our findings suggest that the CTSL2 gene is associated with T1D and with early-onset MG. PMID- 17869650 TI - Interleukin-6 gene variants and the risk of sepsis development in children. AB - A proinflammatory cytokine interleukin-6 (IL-6) plays an important role in the development, pathogenesis and outcome of SIRS, sepsis and septic shock. We have evaluated the role of the IL-6 gene polymorphisms in pediatric patients. A total of 421 consecutive pediatric patients admitted to the pediatric intensive care unit with fever, systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, or multiple organ distress syndrome (MODS) were studied together with 644 healthy controls. DNA was isolated and two IL-6 gene polymorphisms (G-174>C and G-572>C) were analyzed. The frequencies of both analyzed variants differ significantly between the group of patients and healthy controls (p = 0.02 for G-174>C and p = 0.049 for G-572>C). In addition, genetic analysis of the G-174>C IL-6 gene variant revealed significant differences between the subgroup of febrile patients and subgroup of septic shock (p = 0.0319) and between the subgroup of SIRS and septic shock (p = 0.038). In both cases the negative genotype was CC. No statistically significant differences for the IL-6 gene polymorphism G-572>C were found between the groups of patients with different diagnosis. IL-6 gene polymorphisms G-174>C and G-572>C could be the predictors of risk of development and/or the predictors of the severity of sepsis in children. PMID- 17869651 TI - Association of IL-8 (-251)T/A polymorphism with susceptibility to and aggressiveness of nasopharyngeal carcinoma. AB - Interleukin-8 (IL-8) is an angiogenic chemokine that plays a potent role in both development and progression of many human malignancies including nasopharyngeal carcinoma (NPC). In the present study, we evaluated the susceptibility and prognostic implications of the (-251) T/A genetic variation in IL-8 in NPC. We used the allele-specific polymerase chain reaction to characterize the variation of the IL-8 promoter region for 160 unrelated Tunisian patients with NPC and 169 healthy control subjects. There was a significant association between the homozygotes IL-8 (-251) AA genotype and nasopharyngeal carcinoma (OR = 2.46; P = 0.004). The presence of the IL-8 (-251) AA genotype was highly associated with elevated NPC risk for male patients. A significant association was demonstrated between the IL-8 (-251) AA genotype and the aggressive forms of NPC as defined by large tumor size, lymph node metastasis, and advanced stages. Moreover, the presence of the IL-8 (-251) AA genotype indicated a significant association with decreased overall survival. Our findings suggest that the IL-8 promoter polymorphism is associated with increased nasopharyngeal carcinoma risk, particularly in males, as well as disease progress, supporting our hypothesis for IL-8 involvement in NPC pathogenesis. PMID- 17869652 TI - Associations between interferon regulatory factor-1 polymorphisms and Behcet's disease. AB - Interferon regulatory factor-1 (IRF-1) is a transcription factor that regulates the functions of type I and II interferons and plays a role in host protection. Behcet's disease (BD) is an idiopathic systemic vasculitis that is often complicated with thrombotic features, and infectious agents have long been postulated to be a disease-triggering factor in its pathogenesis. The authors investigated the distributions of IRF-1 promoter -415 C/A, -410 A/G, and -300 A/G, and 3'-untranslated region (UTR) A/G polymorphisms in 105 BD patients (mean age 41.7 +/- SEM 1.1 years, 44 male and 61 female) and in 105 gender- and age matched healthy controls. The frequencies of individual alleles and genotypes were not different between the control and BD groups. However, the frequency of AGGG haplotype was significantly higher (73.5% vs 60.2%, odds ratio [OR] = 1.842, 95% confidence interval [95% CI] = 1.219-2.783, p(c) = 0.036) and that of the CAAG haplotype was significantly lower (2.2% vs 9.5%, OR = 0.195, 95% CI = 0.068 0.559, p(c) = 0.02) in BD patients than in healthy controls. In addition, the frequency of the AGGG haplotype was significantly higher (80.3% vs 57.4%, OR = 3.033, 95% CI = 1.716-5.360, p(c) = 0.001) and that of the CAAG haplotype was significantly lower (0.8% vs 12.3%; OR = 0.059, 95% CI = 0.010-0.357, p(c) = 0.005) in female BD patients than female controls. By subgroup analyses, the CAAA haplotype tended to be more common in BD patients with moderate or severe disease than in those with mild disease (25.4% vs 13.6%, OR = 2.158, 95% CI = 1.046 4.440, p = 0.037 before Bonferroni correction). When BD patients were subclassified by a history of deep vein thrombosis (DVT), the CAAA haplotype was found to be significantly increased the risk of DVT (42.1% vs 15.7%, OR = 3.906, 95% CI = 1.836-8.324, p(c) = 0.0015) and the AGGG haplotype tended to reduce this risk (57.9% vs 77.3%, OR = 0.403, 95% CI = 0.195-0.834, p(c) = 0.0685). Furthermore, the frequency of the CAAA haplotype was significantly higher in BD patients that had experienced a thrombotic event than in those that had not (40.5% vs 15.5%, OR = 3.7147, 95% CI = 1.778-7.770, p(c) = 0.0015). These results suggest that IRF-1 is a novel susceptibility gene in BD, especially in women, and furthermore, that IRF-1 polymorphisms may be related to thrombosis in BD patients. PMID- 17869653 TI - High-resolution HLA alleles and haplotypes in the United States population. AB - We extract and present high-resolution HLA allele and haplotype frequency data available from the National Marrow Donor Program databases from four major U.S. census categories of race and ethnicity. Population-based high-resolution HLA frequencies defined on the basis of from one to five loci are presented and made available online (http://bioinformatics.nmdp.org/haplotype2006). In addition, a discriminatory classification of HLA allelic variation on the basis of observed population allele frequencies (common, rare and unseen) for HLA A, C, B, DRB1, DQA1, and DQB1 is introduced. The electronic availability of this information will be useful for projects central to the typing and use of population data in HLA applications. PMID- 17869654 TI - Comprehensive approach to high-resolution KIR typing. AB - Multiple studies suggest that prospective KIR typing may be beneficial for the outcome of bone marrow transplants, but to date no practical high-resolution KIR typing system has been developed. Here we propose a comprehensive high-resolution typing approach that provides allele level KIR typing. Based on the low resolution typing obtained by SSO, the 14 KIR loci are divided in groups according to the level of polymorphism in exons coding for extracellular Ig-like domains and cytoplasmic tail. The first group is typed by sequence-specific oligonucleotide only; the second is typed by sequence-based typing (SBT) based on the amplification of a fragment coding the Ig-like domains; and the third is typed by SBT based on amplification of a fragment coding the cytoplasmic tail. SBT for the fourth group includes both the Ig-like and cytoplasmic domains. Because of a considerable number of polymorphisms scattered throughout all nine KIR exons, SBT results may still produce a number of ambiguities, which can be resolved by sequence-specific primers. This combined high-resolution approach was applied to the complete KIR typing of 205 Caucasian hematopoietic stem cell donors in support of the National Marrow Donor Program High-resolution KIR Typing Pilot Project. High-resolution typing of several KIR loci produced numerous novel alleles, whereas some loci demonstrated very limited polymorphism. Several of the novel alleles appeared in more than four donors, suggesting that these alleles are not rare. Our results showed that the comprehensive KIR typing approach presented here provides the balance of high-resolution typing and cost effectiveness. PMID- 17869658 TI - National Residency Matching Program (NRMP) results for radiation oncology: 2007 update. PMID- 17869659 TI - Metabolic tumor burden predicts for disease progression and death in lung cancer. AB - PURPOSE: In lung cancer, stage is an important prognostic factor for disease progression and survival. However, stage may be simply a surrogate for underlying tumor burden. Our purpose was to assess the prognostic value of tumor burden measured by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging. PATIENTS AND METHODS: We identified 19 patients with lung cancer who had staging PET-CT scans before any therapy, and adequate follow-up (complete to time of progression for 18, and death for 15 of 19). Metabolically active tumor regions were segmented on pretreatment PET scans semi-automatically using custom software. We determined the relationship between times to progression (TTP) and death (OS) and two PET parameters: total metabolic tumor volume (MTV), and standardized uptake value (SUV). RESULTS: The estimated median TTP and OS for the cohort were 9.3 months and 14.8 months. On multivariate Cox proportional hazards regression analysis, an increase in MTV of 25 ml (difference between the 75th and 25th percentiles) was associated with increased hazard of progression and of death (5.4-fold and 7.6-fold), statistically significant (p = 0.0014 and p = 0.001) after controlling for stage, treatment intent (definitive or palliative), age, Karnofsky performance status, and weight loss. We did not find a significant relationship between SUV and TTP or OS. CONCLUSIONS: In this study, high tumor burden assessed by PET MTV is an independent poor prognostic feature in lung cancer, promising for stratifying patients in randomized trials and ultimately for selecting risk-adapted therapies. These results will need to be validated in larger cohorts with longer follow-up, and evaluated prospectively. PMID- 17869660 TI - Intercepting radiotherapy using a real-time tumor-tracking radiotherapy system for highly selected patients with hepatocellular carcinoma unresectable with other modalities. AB - PURPOSE: To assess the clinical outcome of intercepting radiotherapy, in which radiotherapy is delivered only when a tumor in motion enters a target area, using a real-time tumor-tracking radiotherapy (RTRT) system for patients with hepatocellular carcinoma who were untreatable with other modalities because the tumors were adjacent to crucial organs or located too deep beneath the skin surface. METHODS AND MATERIALS: Eighteen tumors, with a mean diameter of 36 mm, were studied in 15 patients. All tumors were treated on a hypofractionated schedule with a tight margin for setup and organ motion using a 2.0-mm fiducial marker in the liver and the RTRT system. The most commonly used dose of radiotherapy was 48 Gy in 8 fractions. Sixteen lesions were treated with a BED(10) of 60 Gy or more (median, 76.8 Gy). RESULTS: With a mean follow-up period of 20 months (range, 3-57 months), the overall survival rate was 39% at 2 years after RTRT. The 2-year local control rate was 83% for initial RTRT but was 92% after allowance for reirradiation using RTRT, with a Grade 3 transient gastric ulcer in 1 patient and Grade 3 transient increases of aspartate amino transaminase in 2 patients. CONCLUSIONS: Intercepting radiotherapy using RTRT provided effective focal high doses to liver tumors. Because the fiducial markers for RTRT need not be implanted into the tumor itself, RTRT can be applied to hepatocellular carcinoma in patients who are not candidates for other surgical or nonsurgical treatments. PMID- 17869661 TI - Prediction of radial distance of extraprostatic extension from pretherapy factors. AB - PURPOSE: Extraprostatic extension (EPE) of tumor conveys an adverse prognosis in early-stage prostate cancer. Previous studies reported on the linear and radial distance of EPE (EPEr) as measured from the prostate edge. In this study, the correlation of the EPEr from a large whole mount prostatectomy series was determined with respect to the needle biopsy and prostatectomy specimen findings. METHODS AND MATERIALS: In a 24-month period, 404 patients underwent radical prostatectomy and the specimens were whole mounted. The preoperative records, biopsy findings, and EPEr from these specimens were evaluated. RESULTS: The range of the EPEr distance was 0.0-5.7 mm. A three-category model was used that included 283 patients (70%) with no EPE, 59 (15%) with "near EPE" (range, 0.01 0.59 mm), and 62 (15%) with "far EPE" (>or=0.6 mm). Univariate analysis revealed that patient age and prostate volume did not correlate with EPEr, in contrast to all other factors evaluated. Multivariate analysis identified the preoperative serum prostate-specific antigen, the percentage of cancer in the biopsy cores, and clinical tumor stage as significant. However, the Gleason score was not associated with the EPEr. Greater discrimination was possible in estimating the probability of extension in the "near" category than in the "far" category. CONCLUSION: EPEr is associated with the preoperative prostate-specific antigen level, percentage of cancer in the biopsy cores, and clinical tumor stage. These data might be useful in planning local therapies for prostate cancer, but additional studies identifying factors associated with EPEr beyond 3-5 mm could have relevance regarding the appropriate radiotherapeutic management strategies. PMID- 17869662 TI - PSA kinetics and PSA bounce following permanent seed prostate brachytherapy. AB - PURPOSE: To report the incidence, timing, and magnitude of the benign prostate specific antigen (PSA) bounce after 125I prostate brachytherapy and correlate the bounce with clinical and/or dosimetric factors. METHODS AND MATERIALS: From March 1999 to August 2003, a total of 292 men received 125I prostate brachytherapy without androgen deprivation or supplemental beam radiotherapy and have PSA follow-up >30 months. Implants were preplanned using transrectal ultrasound (TRUS) and performed under transrectal ultrasound/fluoroscopy guidance using preloaded needles. A PSA bounce is defined as an increase >or=0.2 ng/ml with spontaneous return to prebounce level or lower. RESULTS: Resolved PSA bounces were seen in 40% of men with follow-up >30 months. Median onset was 15 months, and median magnitude was 0.76 ng/ml. Magnitude >2 ng/ml was seen in 15%. The only clinical or dosimetric factor predictive of bounce in multivariate analysis was younger age. Median time to increasing PSA level indicative of failure was 30 months. CONCLUSIONS: Benign PSA bounces are common after 125I prostate brachytherapy, especially in younger men. An increase >2 ng/ml above the nadir was seen in 15%. Magnitude of increase does not distinguish bounce from failure. Time to the start of the PSA increase can be helpful, but is not absolute. The PSA bounce does not predict subsequent failure. Caution is advised in interpreting an early increasing PSA level in the first 30 months after 125I brachytherapy in favorable-risk patients. PMID- 17869663 TI - Stereotactic radiosurgery versus gold grain implantation in salvaging local failures of nasopharyngeal carcinoma. AB - BACKGROUND: Limited local failure of nasopharyngeal carcinoma (NPC) can often be salvaged by reirradiation using different techniques. Both gold grain implantation (GGI) and stereotactic radiosurgery (SRS) have been used as salvage treatment of NPC but the relative efficacy of these two treatments is not known. METHODS AND MATERIALS: A total of 74 patients with local NPC failure were included in this retrospective analysis. Of these patients, 37 underwent SRS (median dose, 12.5 Gy) and 37 split-palatal GGI at a dose of 60 Gy. The two groups were individually matched for prognostic factors, except for tumor volume. The median follow-up was 42 months. RESULTS: Local control was better in the GGI group. The 3-year local failure-free rate was 77.9% for the GGI group compared with 68.3% for the SRS group. However, the difference was not statistically significant (p = 0.098). In the subgroup with a tumor volume of or=50% of the individual preirradiation value) were assessed by cystometry. RESULTS: Early changes in mouse bladder after irradiation occur in two phases. In the first early phase, a single injection of Palifermin on day -2 increased the ED(50) (dose associated with a positive bladder response in 50% of the mice) from 20.0 +/- 3.3 Gy to 27.1 +/- 6.9 Gy (p < .0051). Palifermin given on day +2 was not beneficial. No significant effects of Palifermin were seen in the second early phase. However, Palifermin administration before, but not after, irradiation, also modified late radiation effects, with an ED50 of 22.2 +/- 4.8 Gy compared with 16.2 +/- 4.9 Gy in control animals (p < .0187). CONCLUSIONS: Initial early functional changes in the mouse urinary bladder after irradiation as well as late effects can be significantly reduced by a single administration of Palifermin before irradiation. PMID- 17869666 TI - Radioprotective effects of amifostine on acute and chronic esophageal injury in rodents. AB - PURPOSE: This study was performed to evaluate the protective benefit of amifostine against esophageal injury from fractionated radiation in a rodent model. METHODS: Fractionated or sham esophageal irradiation was administered to Fisher-344 rats for 5 consecutive daily fractions of 9 Gy using 150 kV X-rays. Animals received an intraperitoneal injection of amifostine or placebo 30 min before each fraction. Histopathologic analyses for mucosal thickness, submucosal collagen deposition, activation of macrophages, oxidative stress and expression/activation of integrinalphavbeta6 and transforming growth factor (TGF) beta were performed 5 days and 10 weeks after irradiation. RESULTS: Pre-RT mean mucosal thickness was 35 microm in both the placebo and the amifostine groups. Five days post-RT, mean mucosal thicknesses were 30 microm in the placebo group versus 37 microm in the amifostine group (p = 0.024). At 10 weeks post-RT, the group receiving amifostine experienced a significant decrease in tunica muscularis damage (p = 0.002), submucosal collagen deposition (p = 0.027), and macrophage accumulation (p = 0.026) when compared with the placebo group. The levels of immunoreactivity for oxidative stress, TGF-beta, and integrinalphavbeta6 were significantly decreased 10 weeks post-RT in the group receiving amifostine treatment compared with placebo group. CONCLUSIONS: This study demonstrates that amifostine given before each radiation fraction protects against acute and chronic esophageal injury in a rodent model. Protection of the mucosal epithelium integrity by amifostine prevents integrinalphavbeta6 expression which reduces TGF-beta activation and subsequent development of chronic esophageal injury in this model. Further investigation is necessary to determine the clinical relevance of these findings. PMID- 17869667 TI - Hypoxia imaging with FAZA-PET and theoretical considerations with regard to dose painting for individualization of radiotherapy in patients with head and neck cancer. AB - PURPOSE: To evaluate the role of hypoxia positron emission tomography (PET) using [18F]fluoroazomycin-arabinoside (FAZA) in head and neck cancer for radiation treatment planning using intensity-modulated radiotherapy and dose painting. METHODS AND MATERIALS: Eighteen patients with advanced squamous cell head and neck cancer were included. Both FAZA-PET and axial CT were performed using mask fixation. The data were coregistered using software based on mutual information. Contours of tumor (primary gross tumor volume, GTV/CT-P) and lymph node metastases (GTV/CT-N) were outlined manually, and FAZA standardized uptake values (SUVs) were calculated automatically. The hypoxic subvolume (GTV/PET-FAZA) having at least 50% more FAZA uptake than background (mean SUV) neck muscle tissue was contoured automatically within GTV/CT-P (GTV/PET-FAZA-P) and GTV/CT-N (GTV/PET FAZA-N). RESULTS: The median GTV/PET-FAZA-P was 4.6 mL, representing 10.8% (range, 0.7-52%) of the GTV/CT-P. The GTV/PET-FAZA-P failed to correlate significantly with the GTV/CT-P (p = 0.06). The median GTV/PET-FAZA-N was 4.1 mL, representing 8.3% (range, 2.2-51.3%) of the GTV/CT-N. It was significantly correlated with the GTV/PET-N (p = 0.006). The GTV/PET-FAZA-P was located in a single confluent area in 11 of 18 patients (61%) and was diffusely dispersed in the whole GTV/CT-P in 4 of 18 patients (22%), whereas no hypoxic areas were identified in 3 of 18 patients (17%). The GTV/PET-FAZA-N was outlined as a single confluent region in 7 of 18 patients (39%), in multiple diffuse hypoxic regions in 4 of 18 patients (22%), and was not delineated in 7 of 18 patients (39%). CONCLUSION: This study demonstrates that FAZA-PET imaging could be used for a hypoxia-directed intensity-modulated radiotherapy approach in head and neck cancer. PMID- 17869668 TI - The impact of heart irradiation on dose-volume effects in the rat lung. AB - PURPOSE: To test the hypothesis that heart irradiation increases the risk of a symptomatic radiation-induced loss of lung function (SRILF) and that this can be well-described as a modulation of the functional reserve of the lung. METHODS AND MATERIALS: Rats were irradiated with 150-MeV protons. Dose-response curves were obtained for a significant increase in breathing frequency after irradiation of 100%, 75%, 50%, or 25% of the total lung volume, either including or excluding the heart from the irradiation field. A significant increase in the mean respiratory rate after 6-12 weeks compared with 0-4 weeks was defined as SRILF, based on biweekly measurements of the respiratory rate. The critical volume (CV) model was used to describe the risk of SRILF. Fits were done using a maximum likelihood method. Consistency between model and data was tested using a previously developed goodness-of-fit test. RESULTS: The CV model could be fitted consistently to the data for lung irradiation only. However, this fitted model failed to predict the data that also included heart irradiation. Even refitting the model to all data resulted in a significant difference between model and data. These results imply that, although the CV model describes the risk of SRILF when the heart is spared, the model needs to be modified to account for the impact of dose to the heart on the risk of SRILF. Finally, a modified CV model is described that is consistent to all data. CONCLUSIONS: The detrimental effect of dose to the heart on the incidence of SRILF can be described by a dose dependent decrease in functional reserve of the lung. PMID- 17869669 TI - Oxygen dependence and extravascular transport of hypoxia-activated prodrugs: comparison of the dinitrobenzamide mustard PR-104A and tirapazamine. AB - PURPOSE: To compare oxygen dependence and tissue transport properties of a new hypoxia-activated prodrug, PR-104A, with tirapazamine, and to evaluate the implications for antitumor activity when combined with radiotherapy. METHODS AND MATERIALS: Oxygen dependence of cytotoxicity was measured by clonogenic assay in SiHa cell suspensions. Tissue transport parameters were determined using SiHa multicellular layers. Spatially resolved pharmacokinetic (PK) and pharmacodynamic (PD) models were developed to predict cell killing in SiHa tumors and tested by clonogenic assay 18 h after treatment with the corresponding phosphate ester, PR 104. RESULTS: The K-value (oxygen concentration to halve cytotoxic potency) of PR 104A was 0.126 +/- 0.021 microM (10-fold lower than tirapazamine at 1.30 +/- 0.28 microM). The diffusion coefficient of PR-104A in multicellular layers (4.42 +/- 0.15 x 10(-7) cm2 s(-1)) was lower than that of tirapazamine (1.30 +/- 0.05 x 10( 6) cm2 s(-1)) but PK modeling predicted better penetration to hypoxic cells in tumors because of its slower metabolism. The tirapazamine PK/PD model successfully predicted the measured activity in combination with single-dose radiation against SiHa tumors, and the PR-104A model underpredicted the activity, which was greater for PR-104 than for tirapazamine (at equivalent host toxicity) both with radiation and as a single agent. CONCLUSION: PR-104/PR-104A has different PK/PD properties from tirapazamine and superior activity with single dose radiotherapy against SiHa xenografts. We have inferred that PR-104A is better able to kill cells at intermediate partial pressure of oxygen in tumors than implied by the PK/PD model, most likely because of a bystander effect resulting from diffusion of its activated metabolites from severely hypoxic zones. PMID- 17869670 TI - Therapeutic efficacy of astatine-211-labeled trastuzumab on radioresistant SKOV-3 tumors in nude mice. AB - PURPOSE: To investigate the potential use of astatine-211 (211At)-labeled trastuzumab for the treatment of HER-2-positive, radioresistant ovarian carcinoma. METHODS AND MATERIALS: Four-week-old nude mice were inoculated intraperitoneally with 5 . 10(6) SKOV-3 cells in 0.4 mL saline on Day 0. The endpoint was the total tumor weight in each mouse on Day 63. Three experiments were performed in which the response to single-dose and fractionated treatment with unlabeled and 211At-labeled antibody was evaluated. RESULTS: Experiment 1 showed, for the same total amount of trastuzumab, a dose-response relationship between 211At activity (0-400 kBq on Day 7) and therapeutic efficacy (p = 0.001). The effect of varying the amount of unlabeled trastuzumab was studied in Experiment 2. All mice, except for the controls, received 400 kBq 211At trastuzumab, and different groups received 5, 50, or 500 microg trastuzumab on Day 7. The increase from 5 to 50 microg trastuzumab reduced the tumors by 78% in weight. No tumors were present in mice given 500 microg trastuzumab. In Experiment 3, the effect of a fractionated treatment regimen was studied. Mice that received 100 kBq 211At-trastuzumab on Days 7 and 8 had a 42% smaller tumor burden than did controls. Groups of mice injected with 200 + 100 kBq on Days 7 and 21 and mice injected with 100 kBq on Days 7, 8, and 21 both had 24% less tumor weight than the corresponding controls. CONCLUSION: The combination of 500 microg trastuzumab and 400 kBq 211At-trastuzumab had the greatest effect, with complete eradication of the tumors in this nude mouse model. PMID- 17869671 TI - Assessment of intrafraction mediastinal and hilar lymph node movement and comparison to lung tumor motion using four-dimensional CT. AB - PURPOSE: To quantify the amount of free-breathing motion measured using Four dimensional (4D) CT scans of mediastinal and hilar lymph nodes and to compare this motion to the primary lung tumor motion. METHODS AND MATERIALS: Twenty patients with primary lung cancer, radiographically positive lymph nodes, and prior 4D CT scans were retrospectively analyzed. The 4D CT data sets were divided into four respiratory phases, and the primary tumor and radiographically positive nodes were contoured. Geometric and volumetric analysis was performed to analyze the motion of the primary tumors and the lymph nodes. RESULTS: The mean lymph node motion was 2.6 mm in the mediolateral direction, 2.5 mm in the anterior posterior direction, and 5.2 mm in the cranial-caudal direction with a maximum of 14.4 mm. All lymph nodes were found to move inferiorly during inspiration, with 12.5% of nodes moving more than 1 cm. Lymph nodes located below the carina showed significantly more motion than those above the carina (p = 0.01). In comparing the primary tumor motion to the lymph node motion, no correlation was identified. CONCLUSIONS: Four-dimensional CT scans can be used to measure the motion of the primary lung tumor and pathologic lymph nodes encountered during the respiratory cycle. Both the primary lung tumor and the lymph node must to be examined to assess their individual degree of motion. This study demonstrates the need for individualized plans to assess the heterogeneous motion encountered in both primary lung tumors and among lymph node stations. PMID- 17869672 TI - Whole brain radiotherapy with hippocampal avoidance and simultaneously integrated brain metastases boost: a planning study. AB - PURPOSE: To evaluate the feasibility of using tomotherapy to deliver whole brain radiotherapy with hippocampal avoidance, hypothesized to reduce the risk of memory function decline, and simultaneously integrated boost to brain metastases to improve intracranial tumor control. METHODS AND MATERIALS: Ten patients treated with radiosurgery and whole brain radiotherapy underwent repeat planning using tomotherapy with the original computed tomography scans and magnetic resonance imaging-computed tomography fusion-defined target and normal structure contours. The individually contoured hippocampus was used as a dose-limiting structure (<6 Gy); the whole brain dose was prescribed at 32.25 Gy to 95% in 15 fractions, and the simultaneous boost doses to individual brain metastases were 63 Gy to lesions >or=2.0 cm in the maximal diameter and 70.8 Gy to lesions <2.0 cm. The plans were generated with a field width (FW) of 2.5 cm and, in 5 patients, with a FW of 1.0 cm. The plans were compared regarding conformation number, prescription isodose/target volume ratio, target coverage, homogeneity index, and mean normalized total dose. RESULTS: A 1.0-cm FW compared with a 2.5 cm FW significantly improved the dose distribution. The mean conformation number improved from 0.55 +/- 0.16 to 0.60 +/- 0.13. Whole brain homogeneity improved by 32% (p <0.001). The mean normalized total dose to the hippocampus was 5.9 +/- 1.3 Gy(2) and 5.8 +/- 1.9 Gy(2) for 2.5- and 1.0-cm FW, respectively. The mean treatment delivery time for the 2.5- and 1.0-cm FW plans was 10.2 +/- 1.0 and 21.8 +/- 1.8 min, respectively. CONCLUSION: Composite tomotherapy plans achieved three objectives: homogeneous whole brain dose distribution equivalent to conventional whole brain radiotherapy; conformal hippocampal avoidance; and radiosurgically equivalent dose distributions to individual metastases. PMID- 17869673 TI - On-board patient positioning for head-and-neck IMRT: comparing digital tomosynthesis to kilovoltage radiography and cone-beam computed tomography. AB - PURPOSE: High-precision intensity-modulated radiotherapy demands high patient positioning accuracy. On-board digital tomosynthesis (DTS) provides three dimensional (3D) image guidance for daily positioning with a lower imaging dose, faster acquisition, and more geometric flexibility than 3D cone-beam computed tomography (CBCT). This clinical study evaluated DTS as a daily imaging technique for patient positioning and compared the results with 3D CBCT and two-dimensional (2D) radiography. METHODS AND MATERIALS: Head and neck cancer patients undergoing intensity-modulated radiotherapy were studied. For each session, the patient was positioned using laser marks. On-board imaging data sets, including 2D kilovoltage radiographs, DTS, and CBCT, were obtained to measure the daily patient positioning variations. The mean and standard deviations of the positioning variations in the translational and rotational directions were calculated. The positioning differences among 2D radiography, DTS, and CBCT were analyzed. RESULTS: Image data sets were collected from 65 treatment fractions for 10 patients. The systematic patient positioning variation was <0.10 cm and 1.0 degrees one dimensionally. The random variations were 0.27-0.34 cm in the translational and 0.93 degrees -1.99 degrees in the rotational direction. The mean vector isocenter variation was 0.48 cm. DTS with 40 degrees and 20 degrees scan angles in the coronal or sagittal directions yielded the same results for patient positioning. DTS performance was comparable to that of CBCT, with positioning differences of <0.1 cm and 0.5 degrees . The positioning difference between 2D radiography and DTS was approximately 0.1 cm and 0.2 cm in the vertical/longitudinal and lateral directions. CONCLUSION: Our results have demonstrated that DTS is a comparable 3D imaging technique to CBCT for daily patient positioning of head-and-neck patients as determined by manual registration of bony anatomy. PMID- 17869674 TI - Experimental evaluation of the impact of different head-and-neck intensity modulated radiation therapy planning techniques on doses to the skin and shallow targets. AB - PURPOSE: To investigate experimentally the impact of different head-and-neck intensity-modulated radiation therapy (IMRT) planning techniques on doses to the skin and shallow targets. METHODS AND MATERIALS: A semicylindrical phantom was constructed with micro-MOSFET dosimeters (Thomson-Nielson, Ottawa, Ontario, Canada) at 0-, 3-, 6-, 9-, and 12-mm depths. The planning target volume (PTV) was pulled back 0, 3, or 5 mm from the body contour. The IMRT plans were created to maximize PTV coverage, with one of the following strategies: (a) aim for a maximum 110% hotspot, with 115% allowed; (b) aims for a maximum 105% hotspot; (c) aims for a maximum 105% hotspot and 50% of skin to get a maximum 70% of the prescribed dose; and (d) aim for 99% of the PTV volume to receive 90-93% of prescribed dose, with a maximum 105% hotspot, and with the dose to the skin structure minimized. Doses delivered using a linear accelerator were measured. Setup uncertainty was simulated by intentionally shifting the phantom in a range of +/-8 mm, and calculating the delivered dose for a range of systematic and random uncertainties. RESULTS: From lowest to highest skin dose, the planning strategies were in the order of c, d, b, and a, but c showed a tendency to underdose tissues at depth. Delivered doses varied by 10-20%, depending on planning strategy. For typical setup uncertainties, cumulative dose reduction to a point 6 mm deep was <4%. CONCLUSIONS: It is useful to use skin as a sensitive structure, but a minimum dose constraint must be used for the PTV if unwanted reductions in dose to nodes near the body surface are to be avoided. Setup uncertainties are unlikely to give excessive reductions in cumulative dose. PMID- 17869675 TI - Effect of edema on postimplant dosimetry in prostate brachytherapy using CT/MRI fusion. AB - PURPOSE: To investigate the time course of prostatic edema and the effect on the dose-volume histograms of the prostate for patients treated with brachytherapy. METHODS AND MATERIALS: A total of 74 patients with prostate cancer were enrolled in this prospective study. A transrectal ultrasound-based preplan was performed 4 weeks before implantation and computed tomography/magnetic resonance imaging fusion-based postimplant dosimetry was performed on the day after implantation (Day 1) and 30 days after implantation (Day 30). The prostate volume, prostate volume covered by 100% of the prescription dose (V100), and dose covering 90% of the prostate (D90) were evaluated with prostatic edema over time. RESULTS: Prostatic edema was greatest on Day 1, with the mean prostate volume 36% greater than the preplan transrectal ultrasound-based volume; it thereafter decreased over time. It was 9% greater than preplan volume on Day 30. The V(100) increased 5.7% from Day 1 to Day 30, and the D90 increased 13.1% from Day 1 to Day 30. The edema ratio (postplan/preplan) on Day 1 of low-quality implants with a V(100) of <80% was significantly greater than that of intermediate- to high-quality implants (>80% V100; p = 0.0272). The lower V100 on Day 1 showed a greater increase from Day 1 to Day 30. A V100 on Day 1 of >92% is unlikely to increase >0% during the interval studied. CONCLUSION: Low-quality implants on Day 1 were highly associated with edema; however, such a low-quality implant on Day 1, with significant edema, tended to improve by Day 30. If a high-quality implant (V100 >92%) can be obtained on Day 1, a re-examination is no longer necessary. PMID- 17869676 TI - Treatment planning for MRI assisted brachytherapy of gynecologic malignancies based on total dose constraints. AB - PURPOSE: To develop a method for treatment planning and optimization of magnetic resonance imaging (MRI)-assisted gynecologic brachytherapy that includes biologically weighted total dose constraints. METHODS AND MATERIALS: The applied algorithm is based on the linear-quadratic model and includes dose, dose rate, and fractionation of the whole radiotherapy setting, consisting of external beam therapy plus high-dose-rate (HDR), low-dose-rate (LDR) or pulsed-dose rate (PDR) brachytherapy. Biologically effective doses (BED) are converted to more familiar isoeffective (equivalent) doses in 2-Gy fractions. For individual treatment planning of each brachytherapy fraction, the algorithm calculates the physical dose per brachytherapy fraction that corresponds to a predefined isoeffective total dose constraint. Achieved target dose and sparing of organs at risk of already delivered brachytherapy fractions are incorporated. RESULTS: Since implementation for use in clinical routine in 2001, MRI assisted treatment plans of 216 gynecologic patients (161 HDR, 55 PDR brachytherapy) were prospectively optimized taking into account isoeffective dose-volume histogram-based total dose constraints for high-risk clinical target volume (HR CTV) and organs at risk (bladder, rectum, sigmoid). The algorithm is implemented in a spreadsheet and the procedure is fast and efficient. An uncertainty analysis of the isoeffective total doses based on variations of tissue parameters shows that confidence intervals are larger for PDR compared with HDR brachytherapy. For common treatment schedules, overall uncertainties of high-risk clinical target volume and organs at risk are within 8 Gy, except for the bladder when using the PDR technique. CONCLUSION: The presented method to respect total dose constraints is reliable and efficient and an essential tool when aiming to increase local control and minimize side effects. PMID- 17869677 TI - Evaluation of uncertainty-based stopping criteria for monte carlo calculations of intensity-modulated radiotherapy and arc therapy patient dose distributions. AB - PURPOSE: To formulate uncertainty-based stopping criteria for Monte Carlo (MC) calculations of intensity-modulated radiotherapy and intensity-modulated arc therapy patient dose distributions and evaluate their influence on MC simulation times and dose characteristics. METHODS AND MATERIALS: For each structure of interest, stopping criteria were formulated as follows: sigma(rel) or=95% of the voxels, where sigma(rel) represents the relative statistical uncertainty on the estimated dose, D. The tolerated uncertainty (sigma(rel,tol)) was 2%. The dose limit (D(lim)) equaled the planning target volume (PTV) prescription dose or a dose value related to the organ at risk (OAR) planning constraints. An intensity modulated radiotherapy-lung, intensity-modulated radiotherapy-ethmoid sinus, and intensity-modulated arc therapy-rectum patient case were studied. The PTV stopping criteria-based calculations were compared with the PTV+OAR-stopping criteria-based calculations. RESULTS: The MC dose distributions complied with the PTV-stopping criteria after 14% (lung), 21% (ethmoid), and 12% (rectum) of the simulation times of a 100 million histories reference calculation, and increased to 29%, 44%, and 51%, respectively, by the addition of the OAR-stopping criteria. Dose-volume histograms corresponding to the PTV-stopping criteria, PTV+OAR stopping criteria, and reference dose calculations were indiscernible. The median local dose differences between the PTV-stopping criteria and the reference calculations amounted to 1.4% (lung), 2.1% (ethmoid), and 2.5% (rectum). CONCLUSIONS: For the patient cases studied, the MC calculations using PTV stopping criteria only allowed accurate treatment plan evaluation. The proposed stopping criteria provided a flexible tool to assist MC patient dose calculations. The structures of interest and appropriate values of sigma(rel,tol) and D(lim) should be selected for each patient individually according to the clinical treatment planning goals. PMID- 17869678 TI - Ultrathin hydrocolloid dressing in skin damaged from alternating radiotherapy and chemotherapy plus cetuximab in advanced head and neck cancer (G.O.N.O. AlteRCC Italian Trial): in regard to Macmillan et al. (Int J Radiat Oncol Biol Phys 2007;68:864-872). PMID- 17869679 TI - In regards to Bujko et Al. (Int j radiat oncol biol phys 2007;68:313-316). PMID- 17869681 TI - Is mastectomy superior to breast-conserving treatment for young women? In regard to Coulombe et Al. (Int j radiat oncol biol phys 2007;67:1282-1290). PMID- 17869682 TI - What approach will lead to cure of glioblastoma multiforme? In regard to Barani et al. (Int J Radiat Oncol Biol Phys 2007;68:324-333) and Jones and Sanghera (Int J Radiat Oncol Biol Phys 2007;68:441-448). PMID- 17869966 TI - Intensive care unit safety incidents for medical versus surgical patients: a prospective multicenter study. AB - PURPOSE: The aim of this study is to determine if patient safety incidents and the system-related factors contributing to them systematically differ for medical versus surgical patients in intensive care units. MATERIALS AND METHODS: We conducted a multicenter prospective study of 646 incidents involving adult medical patients and 707 incidents involving adult surgical patients that were reported to an anonymous patient safety registry over a 2-year period. We compared incident characteristics, patient harm, and associated system factors for medical versus surgical patients. RESULTS: The proportion of safety incidents reported for medical versus surgical patients differed for only 3 of 11 categories: equipment/devices (14% vs 19%; P = .02), "line, tube, or drain" events (8% vs 13%; P = .001), and computerized physician order entry (13% vs 6%; P < or = .001). The type of patient harm associated with incidents also did not differ. System factors were similar for medical versus surgical patients, with training and teamwork being the most important factors in both groups. CONCLUSIONS: Medical and surgical patients in the intensive care unit experience very similar types of safety incidents with similar associated patient harm and system factors. Common initiatives to improve patient safety for medical and surgical patients should be undertaken with a specific focus on improving training and teamwork among the intensive care team. PMID- 17869967 TI - Methodological approach for the evaluation of the performances of medical intensive care units. AB - PURPOSE: The purpose of the study was to present a methodological approach enabling the comparison of clinical and economic performances of intensive care units and a graphical visualization based on these 2 dimensions. PATIENTS AND METHODS: A retrospective analysis of a database of 666 patients admitted in intensive care units over a period of 2 consecutive months. RESULTS: Calculation of clinical performance is based on the difference between the mortality observed and forecast from the Simplified Acute Physiology Score version 2. The evaluation of resource consumption is carried out from the measure of medical and paramedical care workload. These 2 scores are modeled on the basis of the length of stay and the severity state of the patient. The economic performance is calculated on the basis of the difference between the resource consumption observed and forecast. The graphs are constructed by taking up as coordinates the values of the clinical and economic performances of each center. CONCLUSION: These graphs enable the identification of the most deviating intensive care units to study, for example, their organizational, technical, or human resource setup accounting for their position. PMID- 17869968 TI - A multicenter survey of Ontario intensive care unit nurses regarding the use of sedatives and analgesics for adults receiving mechanical ventilation. AB - BACKGROUND: Nursing-directed sedation protocols have been shown to reduce the duration of mechanical ventilation and shorten the length of intensive care unit (ICU) stay among critically ill adult patients. METHODS: We designed a self administered questionnaire to understand nurses' satisfaction with current sedation and analgesia practices as well as drug therapies in the ICU setting and the perceived relevance of sedation protocols to patient care and nursing autonomy. We surveyed nurses from 3 academic medical-surgical ICUs that were not using a sedation protocol or a sedation scale. Responses were based on a 5-point Likert scale and on text responses to open-ended questions. RESULTS: Of the 88 respondents, only 52.7% were satisfied (score, > or =4) overall with their local ICU's approach to sedation and analgesia. Nurses favored the use of morphine (85.0%), midazolam (71.2%), and fentanyl (59.6%) over that of lorazepam (38.6%) and haloperidol (15.4%). Some nurses (39.3%) were satisfied with the subjective methods used in their ICU to evaluate sedation adequacy. Almost all respondents believed that a nursing-directed sedation protocol combined with a sedation/agitation scoring system would be valuable to patient care (84.3%) as well as professional nursing practice (85.3%) and that a standardized approach by nurses and physicians was important (81.6%). CONCLUSIONS: In this survey of ICU nurses, we identified a perceived need for improvement in sedation and analgesia practices. Most respondents believed that the use of a nursing-directed sedation protocol in combination with a sedation scoring system would provide greater practice consistency among nurses and physicians and thus improve the care of critically ill patients. PMID- 17869969 TI - The COASST study: cost-effectiveness of albumin in severe sepsis and septic shock. AB - INTRODUCTION: The cost-effectiveness of albumin-based fluid support in patients with severe sepsis is not known. METHODS: We compared standard medical practice and systematic albumin infusion. The study population consisted of patients with severe sepsis and/or septic shock admitted to one of the 35 intensive care units belonging to the Cub-Rea regional database between 1 January 1998 and 31 December 2002. Only stays longer than 24 hours and only patients with a minimum of circulatory, renal, or respiratory failure were considered. Cost estimates were based on French diagnosis-related groups and fixed daily prices. A 4.6% reduction in mortality was expected in the albumin arm, as observed in the Saline vs Albumin Fluid Evaluation (SAFE) Study. Life expectancy was estimated with the declining exponential approximation of life expectancy method, based on age, sex, Simplified Acute Physiology Score II, and McCabe score. RESULTS: The number of lives saved among the 11137 patients was 513. The average life expectancy of the 5156 patients who left the hospital alive was estimated to be 9.78 years. The costs per life saved and per year life saved were 6037 euro and 617 euro, respectively. Sensitivity analyses confirmed the robustness of the results. CONCLUSION: The application of the SAFE Study results to CUB-Rea data shows that albumin infusion is cost-effective in severe sepsis. PMID- 17869970 TI - Family satisfaction in the intensive care unit: cross-cultural adaptation of a questionnaire. AB - PURPOSE: Family needs and expectations are often unmet in the intensive care unit (ICU), leading to dissatisfaction. This study assesses cross-cultural adaptability of an instrument evaluating family satisfaction in the ICU. MATERIALS AND METHODS: A Canadian instrument on family satisfaction was adapted for German language and central European culture and then validated for feasibility, validity, internal consistency, reliability, and sensitivity. RESULTS: Content validity of a preliminary translated version was assessed by staff, patients, and next of kin. After adaptation, content and comprehensibility were considered good. The adapted translation was then distributed to 160 family members. The return rate was 71.8%, and 94.4% of questions in returned forms were clearly answered. In comparison with a Visual Analogue Scale, construct validity was good for overall satisfaction with care (Spearman rho = 0.60) and overall satisfaction with decision making (rho = 0.65). Cronbach alpha was .95 for satisfaction with care and .87 for decision-making. Only minor differences on repeated measurements were found for interrater and intrarater reliability. There was no floor or ceiling effect. CONCLUSIONS: A cross-cultural adaptation of a questionnaire on family satisfaction in the ICU can be feasible, valid, internally consistent, reliable, and sensitive. PMID- 17869971 TI - The provision of critical care outreach services in England: findings from a national survey. AB - PURPOSE: The aim of this study was to describe the development, introduction, implementation, and current models of critical care outreach services. MATERIALS AND METHODS: We conducted a national postal survey of National Health Service acute care hospitals in England that routinely provide care for level 1 patients (n = 239). RESULTS: Completed questionnaires were received from 191 (79.9%) hospitals; 139 (72.8%) had a formal critical care outreach service. A third (32.8%, 45/137) of services covered more than one hospital; 33.8% (45/133) of hospitals provided telephone advice 24 hours a day for 7 days per week, but less than 15% of hospitals offered follow-up or direct bedside clinical support on the same basis. There was wide variation in the proportion of hospital wards covered, the size and composition of the team, the aims of the service, and the balance between provision of direct care and advice. CONCLUSIONS: There are still a significant number of National Health Service acute care hospitals in England with no formal critical care outreach service. In addition, critical care outreach is being delivered in many different ways across the country, and thus means different things in different hospitals. The variation may reflect the lack of evidence as to which approaches are likely to be most effective. PMID- 17869972 TI - Sedation and weaning from mechanical ventilation: effects of process optimization outside a clinical trial. AB - PURPOSE: We studied the effects of reorganization and changes in the care process, including use of protocols for sedation and weaning from mechanical ventilation, on the use of sedative and analgesic drugs and on length of respiratory support and stay in the intensive care unit (ICU). MATERIALS AND METHODS: Three cohorts of 100 mechanically ventilated ICU patients, admitted in 1999 (baseline), 2000 (implementation I, after a change in ICU organization and in diagnostic and therapeutic approaches), and 2001 (implementation II, after introduction of protocols for weaning from mechanical ventilation and sedation), were studied retrospectively. RESULTS: Simplified Acute Physiology Score II (SAPS II), diagnostic groups, and number of organ failures were similar in all groups. Data are reported as median (interquartile range). Time on mechanical ventilation decreased from 18 (7-41) (baseline) to 12 (7-27) hours (implementation II) (P = .046), an effect which was entirely attributable to noninvasive ventilation, and length of ICU stay decreased in survivors from 37 (21-71) to 25 (19-63) hours (P = .049). The amount of morphine (P = .001) and midazolam (P = .050) decreased, whereas the amount of propofol (P = .052) and fentanyl increased (P = .001). Total Therapeutic Intervention Scoring System-28 (TISS-28) per patient decreased from 137 (99-272) to 113 (87-256) points (P = .009). Intensive care unit mortality was 19% (baseline), 8% (implementation I), and 7% (implementation II) (P = .020). CONCLUSIONS: Changes in organizational and care processes were associated with an altered pattern of sedative and analgesic drug prescription, a decrease in length of (noninvasive) respiratory support and length of stay in survivors, and decreases in resource use as measured by TISS-28 and mortality. PMID- 17869974 TI - Hypothermia in severe traumatic brain injury: questions remain. PMID- 17869973 TI - Effects of therapeutic mild hypothermia on patients with severe traumatic brain injury after craniotomy. AB - PURPOSE: We investigated the effects of therapeutic mild hypothermia on patients with severe traumatic brain injury after craniotomy (TBI). METHODS: Eighty patients with severe TBI after unilateral craniotomy were randomized into a therapeutic hypothermia group with the brain temperature maintained at 33 degrees C to 35 degrees C for 4 days, and a normothermia control group in the intensive care unit. Vital signs, intracranial pressure, serum superoxide dismutase level, Glasgow Outcome Scale scores, and complications were prospectively analyzed. RESULTS: The mean intracranial pressure values of the therapeutic hypothermia group at 24, 48, and 72 hours after injury were much lower than those of the control group (23.49 +/- 2.38, 24.68 +/- 1.71, and 22.51 +/- 2.44 vs 25.87 +/- 2.18, 25.90 +/- 1.86, and 24.57 +/- 3.95 mm Hg; P = .000, .000, and .003, respectively). The mean serum superoxide dismutase levels of the therapeutic hypothermia group at days 3 and 7 were much higher than those of the control group at the same time point (533.0 +/- 103.4 and 600.5 +/- 82.9 vs 458.7 +/- 68.1 and 497.0 +/- 57.3 mug/L, respectively; P = .000). The percentage of favorable neurologic outcome 1 year after injury was 70.0% and 47.5%, respectively (P = .041). Complications, including pulmonary infections (57.5% in the therapeutic hypothermia group vs 32.5% in the control group; P = .025) were managed without severe sequelae. CONCLUSIONS: Therapeutic mild hypothermia provides a promising way in the intensive care unit for patients with severe TBI after craniotomy. PMID- 17869975 TI - Invasive candidiasis treated in the intensive care unit: observations from a randomized clinical trial. AB - OBJECTIVES: The objectives of this study were to contrast risk factors, microbiology, and outcomes in patients with invasive candidiasis treated in an intensive care unit (ICU) with those in patients with invasive candidiasis treated outside an ICU and to describe therapeutic results with caspofungin in ICU patients. MATERIALS AND METHODS: We retrospectively identified patients with documented invasive candidiasis who received their first dose of the study drug in the ICU as part of a double-blind randomized trial. Participants were not stratified at entry by their ICU status. Patients received caspofungin (50 mg/d after a 70-mg loading dose) or conventional amphotericin B (0.6-1.0 mg/kg per day) for 10 to 14 days. A favorable response required resolution of signs and symptoms as well as eradication of Candida pathogens. RESULTS: Of the 224 patients, 97 (43%) received their first dose of the study drug in the ICU. Most patients had well-recognized risk factors for invasive candidiasis, including broad-spectrum antibiotics, central venous catheters, and hyperalimentation. Recent surgery was more common whereas malignancy, neutropenia, and immunosuppression were less common among ICU patients than among non-ICU patients. Candidemia was demonstrated in 81% of ICU patients and in 84% of non ICU patients. Favorable response rates in the ICU patients vs the non-ICU patients were 68% (95% confidence interval [CI] = 53%, 82%) vs 77% (95% CI = 67%, 87%) for caspofungin and 56% (95% CI = 43%, 69%) vs 67% (95% CI = 55%, 79%) for amphotericin B. After accounting for differences in APACHE (Acute Physiology and Chronic Health Evaluation) II score, neutropenia status, and geographic region, we found that patients initiating the study therapy in an ICU were still more likely to die than patients initiating study therapy outside an ICU. For ICU patients, all-cause mortality rates were 45% (95% CI = 30%, 60%) for caspofungin recipients and 40% (95% CI = 28%, 53%) for amphotericin B recipients, whereas candidiasis-attributable mortality rates were 5% (95% CI = 0%, 12%) for caspofungin recipients and 11% (95% CI = 3%, 19%) for amphotericin B recipients. Overall, drug-related adverse events were reported less often among the ICU patients than among the non-ICU patients. CONCLUSIONS: In ICU patients treated with antifungal therapy, invasive candidiasis is associated with substantial mortality, but most deaths cannot be directly attributed to this infection. PMID- 17869976 TI - Susceptibility patterns of Candida species recovered from Canadian intensive care units. AB - OBJECTIVE: The objective of this study was to determine the speciation and susceptibility patterns of Candida species recovered from Canadian intensive care units (ICUs) during a 1-day point-prevalence study on fungal colonization/infection in Canadian ICUs. METHODS AND SETTING: Blood, urine, respiratory tract, rectal, and wound fungal cultures were performed for 357 patients present at any time during a single-day 24-hour period in 35 Canadian ICUs. Comparative in vitro activities of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, micafungin, anidulafungin, and aminocandin were determined. RESULTS: Four hundred fifteen yeasts (409 Candida species and 6 non-Candida yeasts) were recovered. Almost 50% of the patients were found to have positive respiratory tract or rectal cultures. Candida albicans accounted for 72% of the Candida species isolated, followed by Candida glabrata (16%), Candida tropicalis (5%), Candida parapsilosis (3%), Candida krusei (2%), and other Candida species or nonspeciated isolates (2%). Minimum inhibitory concentrations (milligrams per liter) at which 90% of the strains were inhibited were 0.06 for micafungin as well as anidulafungin, 0.12 for voriconazole, 0.25 for itraconazole, posaconazole, as well as aminocandin, 1 for amphotericin B, and 4 for fluconazole. Only 4% of the isolates were resistant to fluconazole and/or itraconazole. CONCLUSIONS: Candida albicans is the predominant species colonizing Canadian ICU patients. Overall, the triazoles, both older and new compounds, and the echinocandins have excellent in vitro antifungal activities against Candida species recovered from Canadian ICUs patients. PMID- 17869977 TI - Isolation of Candida species from critically ill patients. PMID- 17869978 TI - Patient-ventilator synchrony during pressure-targeted versus flow-targeted small tidal volume assisted ventilation. AB - PURPOSE: Low tidal volume (V(T)) delivered by flow-targeted breaths reduces ventilator-induced lung injury but may increase patient breathing effort because of limited flow. We hypothesized that a variable-flow, pressure-targeted breath would improve breathing effort versus a fixed flow-targeted breath. MATERIALS AND METHODS: We compared pressure assist-control ventilation and volume assist control ventilation (VACV) in 12 patients with acute respiratory failure receiving 6 to 8 mL/kg V(T). Backup frequency, V(T), inspiratory time, applied positive end-expiratory pressure and fraction of inspired oxygen were held constant. Patient breathing effort was assessed by airway pressure (Paw) drop below baseline 0.1 second after the breath initiation (P(0.1)), the maximal Paw drop during the triggering phase (Ptr), the magnitude of ventilator work during flow delivery, and the presence of an active expiratory effort during cycling and air trapping judged by the magnitude of residual flow at end-expiration. RESULTS: Compared with VACV, pressure assist-control ventilation decreased P(0.1), Ptr (by 25% and 16%, respectively), and evidence for trapped gas but not ventilator work during flow delivery or cycle dys-synchrony. Peak inspiratory flow was comparable between the 2 modes. CONCLUSIONS: In patients receiving small V(T) VACV with increased breathing effort, variable-flow, pressure-targeted ventilation may provide more comfort by decreasing respiratory drive during the triggering phase. PMID- 17869979 TI - Performance of heated wire humidifiers: an in vitro study. AB - PURPOSE: We assessed the performance of heated wire humidifiers (HWHs), which should avoid water condensation in the circuit. METHODS: We evaluated the efficiency of 3 HWHs, MR850 (Fisher & Paykel, Auckland, New Zealand), CONCHATHERM IV (Hudson RCI, Temecula, Calif), and DAR HC 2000 (Mallinckrodt DAR, Mirandola, Italy), in comparison with that of the MR730 heated humidifier (HH), which has a standard circuit. We measured gas temperature and absolute humidity (AH) at the Y piece of the ventilatory circuit using a test lung ventilated at 2 minute ventilation volumes (5 and 15 L/min). Temperature levels at the Y piece of the ventilatory circuit of the HHs were set at 35 degrees C, 37 degrees C, and 39 degrees C with different gradients (-2 degrees C, 0 degrees C, and +2 degrees C) between the outlet chamber and the Y piece of the ventilatory circuit. RESULTS: At the set temperature levels of 35 degrees C, 37 degrees C, and 39 degrees C with a gradient of 0 degrees C, the MR850 and CONCHATHERM IV had lower gas temperature and AH levels as compared with the DAR HC 2000 and MR730 HH. With increasing temperature gradient, gas temperature increased only with the CONCHATHERM IV but AH increased with all the HWHs. The MR850 showed lower gas temperature and AH levels as compared with CONCHATHERM IV. The condensate was abolished inside the inspiratory circuit with the HWHs. CONCLUSIONS: Heated wire humidifiers eliminate water condensation but present significant differences in gas temperature and AH levels that are lower than the expected settings. PMID- 17869980 TI - The white elephant in the room. PMID- 17869981 TI - Comparison of the effects of desflurane and sevoflurane on the expression of platelet surface glycoproteins in unstimulated and adenosine diphosphate-induced platelets in vitro. AB - STUDY OBJECTIVE: To compare the effects of one minimum alveolar concentration (MAC) desflurane and sevoflurane on the expression of CD42b (glycoprotein [GP] Ib), CD41 (GPIIb), CD61 (GPIIIa), CD62P (P-selectin), and CD63 in both unstimulated and adenosine diphosphate (ADP)-stimulated platelets in vitro. SETTING: University laboratory. SUBJECTS: 15 healthy volunteers. INTERVENTIONS: Platelet-rich plasma was obtained and divided into three groups: platelet-rich plasma exposed to air (group 1); air plus one MAC desflurane (6% vol; group 2), and air plus one MAC sevoflurane (2% vol; group 3), for 40 minutes. Percentage of antigen-positive cells (%(+)) mean channel fluorescence (MCF(Sigma)), and index of platelet activation for positive platelets (IPA(+)) as expression markers for GPIb, GPIIb, GPIIIa, P-selectin, and CD63, were measured. MEASUREMENTS AND MAIN RESULTS: In unstimulated platelets, expression markers for GPIIb and GPIIIa were significantly lower in groups 2 and 3 than group 1 (P < 0.001). P-selectin expression markers were significantly higher in group 2 than in group 1 or group 3 (P < 0.016). CD63 expression markers were significantly lower in group 3 than group 1 (P < 0.016). In ADP-stimulated platelets, expression markers for all glycoproteins were significantly higher in all groups. CONCLUSION: Neither one MAC desflurane nor sevoflurane showed any significant change in ADP-stimulated platelets compared with the control group. PMID- 17869982 TI - Work stress and gender-dependent coping strategies in anesthesiologists at a university hospital. AB - STUDY OBJECTIVE: To evaluate stressors and coping strategies for stress in a sample of anesthesiologists working at a university hospital. DESIGN: Cross sectional study via survey instrument. SETTING: University department of anesthesiology and critical care at a 1305-bed hospital. PARTICIPANTS: 135 anesthesia specialists and specialist trainees of anesthesia. MEASUREMENTS AND MAIN RESULTS: A total of 135 self-reporting questionnaires used to assess sociodemographic data, workload, task demands, stress-coping strategies, physical health, emotional well-being, and working conditions, were distributed. Of these, 89 questionnaires were completed and returned, for a response rate of 65.9%: 33 (37.1%) female anesthesiologists and 56 (62.9%) male anesthesiologists. The burden of task-related stressors and of communication possibilities was assessed differently by male and female anesthesiologists. Female anesthesiologists more frequently reported higher concentration demands (P = 0.013) and limited possibilities to control work (P = 0.009) than did their male colleagues. Work at intensive care units (P = 0.001) was particularly demanding and burdensome for female anesthesiologists. Combined evaluation of various stress-coping strategies did not show significant differences between the genders. Generally, anesthesiologists had more confidence in their own personal capabilities and resources and in their social-particularly family-support outside the workplace, than in their social support from colleagues and superiors. CONCLUSIONS: Task related stressors and communication possibilities differed between male and female anesthesiologists in our institution. Female anesthesiologists felt that they had less control over their work. PMID- 17869983 TI - Dental injury associated with anesthesia: a report of 161,687 anesthetics given over 14 years. AB - STUDY OBJECTIVE: To determine the frequency, outcomes, and risk factors for dental injury related to anesthesia. DESIGN: Case-control study. SETTING: Tertiary-care university hospital. PATIENTS: Patients who had a perianesthetic dental injury between August of 1989 and December 31, 2003. MEASUREMENTS: A 1:2 case control study was done to identify the frequency, outcomes, and risk factors for dental injury. Perianesthetic dental injuries were defined as any notable change to the patient's dentition during the perianesthetic period that may or may not have required dental consultation or treatment. MAIN RESULTS: Seventy eight patients with perianesthetic dental injury were identified. The incidence of dental injury was one per 2,073 anesthetics. Eighty-six percent of dental injuries were discovered by the anesthesia provider. Maxillary incisors were the most frequently injured teeth. The most commonly reported injuries were enamel fracture, loosened or subluxated teeth, tooth avulsion, and crown or root fracture. Patients with poor dentition or reconstructive work, whose tracheas were moderately difficult or difficult to intubate, were at much higher risk (approximately 20-fold) of dental injury than those with good dentition and found to be easy to intubate. Among those whose tracheas were easy to intubate, patients with poor dentition or reconstructive work were 3.4 times more likely to have dental injuries related to anesthesia. CONCLUSIONS: Dental injury is one of the most common adverse events reported in association with anesthesia. Risk factors include preexisting poor dentition or reconstructive work and moderately difficult to difficult intubation. PMID- 17869984 TI - Antibacterial activity of remifentanil and mixtures of remifentanil and propofol. AB - STUDY OBJECTIVE: To investigate the antibacterial activity of glycine, which is contained in remifentanil, when combined with propofol. DESIGN: Prospective study. SETTING: Departments of anesthesiology and microbiology of a university hospital. MEASUREMENTS: Growth of the microorganisms Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans in propofol 1%; saline dilutions of remifentanil at one-, 10-, and 100 microg/mL concentrations; and 1:1 mixtures of propofol with remifentanil solutions was determined. MAIN RESULTS: Remifentanil inhibits bacterial growth in a concentration-dependent manner. The antibacterial effects were more pronounced with Staphylococcus aureus and Pseudomonas aeruginosa at cultures obtained at the fifth hour. The inhibition of bacterial growth was less influenced with Escherichia coli and Candida albicans. CONCLUSIONS: Propofol and remifentanil mixtures decreased bacterial growth, and combinations may reduce the infectious complications from accidentally contaminated propofol. PMID- 17869985 TI - Anesthetic considerations during percutaneous nephrolithotomy. AB - STUDY OBJECTIVE: To assess anesthesia-related complications during and following percutaneous nephrolithotomy (PCNL) for staghorn stones. DESIGN: Prospective study and a detailed case report. SETTING: Medical center in southern Israel. PATIENTS: 20 consecutive patients undergoing PCNL for staghorn stones. INTERVENTIONS: All patients underwent PCNL during general anesthesia. MEASUREMENTS: Duration of surgery, esophageal temperature, hemoglobin (Hb) concentration, and requirements for blood transfusion, mean volume of irrigation fluid, and serum sodium and potassium concentration were recorded. MAIN RESULTS: Mean age was 50.7 +/- 14.9 y (range, 26-76 y). Mean duration of the procedure was 120.0 +/- 42.5 min (range, 75-240 min). Mean volume of irrigation fluid was 34.1 +/- 15.3 L (range, 18-80 L). There was a significant decrease in Hb concentration from 13.7 +/- 1.71 to 12.2 +/- 1.4 g/dL, but no patient required blood transfusion. There was a statistically significant reduction in esophageal temperature from 36.4 degrees C +/- 0.32 degrees C to 35.2 degrees C +/- 0.5 degrees C. There were no significant changes in sodium or potassium concentration before or after PCNL. CONCLUSIONS: Anesthesia during PCNL for staghorn stones is a challenge because of the possibility of fluid absorption, dilutional anemia, hypothermia, or significant blood loss. PMID- 17869986 TI - Changing patterns of postoperative nausea and vomiting prophylaxis drug use in an academic anesthesia practice. AB - STUDY OBJECTIVE: To characterize the evolution of postoperative nausea and vomiting (PONV) prophylactic drug use. DESIGN: Retrospective data extraction and analysis of electronic anesthesia records. SETTING: Anesthesia department of an urban academic medical center. MEASUREMENTS: 144,134 anesthetics given by 57 attending anesthesiologists were studied. Administered doses of droperidol, ondansetron, dexamethasone, and metoclopramide were tabulated for each year for each practitioner. MAIN RESULTS: Ondansetron use in the periods before and after the Food and Drug Administration (FDA) warning concerning droperidol was 8% and 35%, respectively. Use of PONV prophylaxis increased for all included patient and anesthetic factors. Among those who used droperidol before the revised FDA warning, 61% stopped using it altogether. Afterwards, 75% (27-100%) of droperidol use was in combination with another agent. CONCLUSIONS: We found a significant and sustained decrease in droperidol use after the FDA-mandated labeling revision. We also found a significant increase in ondansetron use--an increase that exceeded the amount needed to substitute for the decreased droperidol use. The changes may be related to multiple factors, including the FDA warning, a trend toward more PONV prophylaxis, and the increasing predominance of serotonin antagonists for this indication. PMID- 17869987 TI - The safety of reused endotracheal tubes sterilized according to Centers for Disease Control and Prevention guidelines. AB - STUDY OBJECTIVE: To investigate safety issues associated with the reuse of sterilized endotracheal tubes (ETTs). DESIGN: Prospective, randomized study. SETTING: Laboratory in vivo testing. INTERVENTION: Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa were inoculated onto ETT cuffs. Following inoculation, ETTs were sterilized with either ethylene oxide or glutaraldehyde. Cuffs were then swabbed and cultured for 24 hours. To examine changes in the physical integrities of sterilized ETT cuffs, ETTs were sterilized with ethylene oxide gas once, twice, or three times (the E1, E2, and E3 groups, respectively). Alternatively, ETTs were soaked in glutaraldehyde for 150, 300, 450, or 600 minutes (the G1, G2, G3, and G4 groups, respectively). MEASUREMENTS: Endotracheal tube cuffs were considered nonsterile if a visible colony of test organisms was cultured, and sterile if no colony was cultured. Changes in the physical integrity of sterilized ETT cuffs were determined by measuring changes in intracuff pressure or tensile strength. MAIN RESULTS: No growth of bacteria was observed in sterilized tubes. Endotracheal tube cuffs of the E1 and E2 groups showed almost the same physical integrity as those of the control group, whereas E3 group cuffs were softer than those of the untreated controls. Endotracheal tube cuffs of the G1 and G2 groups were harder than untreated controls; than of those of the G3 and G4 groups were similar to the controls. CONCLUSIONS: Endotracheal tubes can be reused sterilized safely. The physical integrity of ETT cuffs may be compromised by glutaraldehyde or ethylene oxide sterilization treatments. PMID- 17869988 TI - Acute uvular edema after regional anesthesia. AB - Acute edema of the uvula may cause respiratory distress and is known to be a rare complication of general anesthesia. This is the first report of acute uvular edema presenting immediately after a regional anesthetic. PMID- 17869989 TI - Airway management in a 980-lb patient: use of the Aintree intubation catheter. AB - We report a 22-year-old, 980-lb (445 kg) man with a body mass index of 163 kg/m(2), who needed intubation for tracheotomy surgery, as he was profoundly hypercarbic and reliant on a tight-fitting continuous positive airway pressure mask. Attempts at oral and nasal fiberoptic intubation during topical anesthesia were unsuccessful because of poor patient cooperation and epistaxis. Thus, after awake placement of a size 5 Laryngeal Mask Airway ProSeal LMA; (LMA North America, San Diego, CA), we induced anesthesia using sevoflurane. Then we placed an Aintree stylet (Cook Critical Care, Bloomington, IN) over a fiberoptic bronchoscope, and both were introduced through the LMA into the trachea. We then removed the fiberoptic bronchoscope followed by the LMA. A Parker size 7.5 endotracheal tube was then "railroaded" over the Aintree catheter into the trachea. PMID- 17869990 TI - Dexmedetomidine as sole sedative for awake intubation in management of the critical airway. AB - We report a series of successful awake fiberoptic intubations in patients with critical (unstable, difficult) airways using the alpha(2)-agonist, dexmedetomidine. Dexmedetomidine has several desirable pharmacologic properties, including sedation, anxiolysis, hypnosis, analgesia, amnesia, antisialagogue effects, and a unique respiratory-sparing effect. Dexmedetomidine appears to be a useful agent for sedation during awake fiberoptic intubation in difficult airway patients. PMID- 17869991 TI - Intractable intraoperative hypoxemia secondary to pulmonary embolism in the presence of undiagnosed patent foramen ovale. AB - The management of a patient with hip fracture during general anesthesia, who developed severe intractable hypoxemia caused by intraoperative pulmonary embolism in the presence of undiagnosed patent foramen ovale, is described. The role of urgent intraoperative transesophageal echocardiography in situations where acute perioperative pulmonary embolism/patent foramen ovale is suspected is emphasized. PMID- 17869992 TI - Intraoperative loss of nasal jewelry: anesthetic concerns and airway management. AB - There are several reports and recommendations regarding body jewelry and its problems posed to anesthesiologists in airway management. We present a case in which the nasal jewelry was lost during surgery and the loss was unnoticed. The loss was confirmed after discussion with the patient's daughter. Results of radiologic and endoscopic studies of head/neck and chest were negative. The missing piece was entangled in the nasogastric tube and was located at the time of the tube's removal. PMID- 17869993 TI - Ultrasound as the only nerve localization technique for peripheral nerve block. AB - Ultrasound facilitates the performance of peripheral nerve blocks and may increase block quality parameters. In this report, we show that ultrasonographic guidance makes peripheral nerve blocks possible in patients in whom the traditional methods of nerve localization are limited. Four cases are described in which conventional end points for successful blocks would have been impossible to use, whereas ultrasound guidance was successful and safe. The latter method increases applicability in a larger group of patients. PMID- 17869994 TI - A tale of two stents: perioperative management of patients with drug-eluting coronary stents. AB - Drug-eluting stents were introduced into clinical practice to decrease coronary stent restenosis rates. Though remarkably effective in reducing this complication, recent data reveal that drug-eluting stents pose a significant risk for late stent thrombosis, an event strongly correlated with discontinuation of anti-platelet therapy. Because anti-platelet agents are often discontinued perioperatively, patients with DES are at risk for perioperative stent thrombosis and myocardial infarction. Along with a review of the recent literature, we present two cases of patients with drug-eluting stents scheduled for renal transplantation. Two distinct antithrombotic management strategies illustrate the risk of either approach-bleeding and transfusion versus stent thrombosis and myocardial infarction. PMID- 17869995 TI - Understanding modes of moderate sedation during gastrointestinal procedures: a current review of the literature. AB - Recommendations for routine screening for colorectal cancer with colonoscopy are likely to substantially increase the demand for provision of sedation for these procedures. Because of this burgeoning caseload and associated economic constraints, it is unlikely that anesthesiologists will be available for all such procedures, particularly those involving average-risk patients. Thus, sedative agents that can be safely administered by nonanesthesiologists, appropriately trained in monitoring and managing the patient's airway, are desperately needed. New concepts in sedation for colonoscopy include enhanced mechanisms for drug delivery such as patient-controlled sedation/analgesia and target-controlled infusion, along with the development of new drugs such as a modified cyclodextrin based formulation of propofol and fospropofol disodium (Aquavan Injection), a water-soluble prodrug of propofol. PMID- 17869996 TI - Anesthetic management of a parturient with neurofibromatosis 1 and Charcot-Marie Tooth disease. PMID- 17869997 TI - Increased risk of venous oxygen embolism with the use of hydrogen peroxide in sitting position. PMID- 17869998 TI - Pain, epidural analgesia and late termination of pregnancy: a new challenge for obstetric anaesthesiologists. PMID- 17870001 TI - Etiologic classification of degenerative mitral valve disease: Barlow's disease and fibroelastic deficiency. AB - Barlow's disease and fibroelastic deficiency are the two dominant forms of degenerative mitral valve disease and have unique differentiating characteristics on clinical and echocardiographic assessment. Preoperative differentiation of patients by both cardiologists and surgeons is important because the techniques, surgical skill, and expertise required to achieve a repair vary among these etiological subsets. Barlow's patients often have multiple complex lesions, thus high rates of repair are only likely to be achieved by a reference mitral valve repair surgeon. In contrast, many forms of fibroelastic disease should be repaired at a high rate by experienced general cardiac surgeons. In this article, we highlight the differentiation of Barlow's disease and fibroelastic deficiency. PMID- 17870002 TI - Indications for surgery in degenerative mitral valve disease. AB - There has been great progress during the past decade in management of patients with mitral regurgitation. Doppler echocardiography allows accurate quantification of the degree of valve leakage and tracking of the effect of regurgitation on cardiac size and function. Natural history studies have clearly delineated the deleterious effects of severe, persistent mitral valve regurgitation including an increased risk of cardiac death as well as a predisposition to the development of congestive heart failure and atrial fibrillation. In virtually all of our analyses, short-term and long-term outcomes are improved in patients who have early surgical correction of severe mitral valve regurgitation. Moreover, there are clear benefits of mitral valve repair over valve replacement, including greater regression of left heart dimensions, normalization of left ventricular function, and superior long-term survival. PMID- 17870003 TI - Principles of reconstructive surgery in degenerative mitral valve disease. AB - Degenerative mitral valve disease is the most common cause of mitral regurgitation (MR) in developed countries. The most common etiologies of valvular regurgitation are Barlow's disease and fibroelastic deficiency. The mechanism of MR is type II dysfunction (leaflet prolapse) due to chordae elongation or rupture in most patients. Associated annular dilation is a common lesion in almost all patients with chronic MR. By means of segmental valve analysis, isolated posterior leaflet prolapse (P2 segment) is often observed in patients with fibroelastic deficiency, whereas the prolapse of multiple segments or bileaflet prolapse is typically seen in patients with Barlow's disease. In patients with degenerative mitral valve disease and severe MR, reconstructive surgery should be performed before the occurrence of clinical symptoms, atrial fibrillation, pulmonary hypertension, and left ventricular dysfunction or enlargement. The goals of reconstructive surgery are preservation or restoration of normal leaflet motion, creation of a large surface of coaptation, and stabilization of the entire annulus with a remodeling annuloplasty. Today, reconstructive techniques are standardized, reliable, and reproducible, and therefore should be applied systematically to all patients with degenerative valvular disease. PMID- 17870004 TI - Gore-tex chordoplasty in degenerative mitral valve repair. AB - Mitral valve repair with Gore-Tex (W.L. Gore & Assoc, Inc, Flagstaff, AZ) neochordae is of increasing interest. In 2000, the loop technique using premeasured Gore-Tex neochordae was introduced by our group. Herein, we report our experience with this technique in minimally invasive mitral valve repair (MVR) for degenerative disease. Between 1999 and 2006, 468 patients (328 men and 140 women) underwent elective MVR using neochordae at our institution. The mean age of the patients was 58 +/- 12.3 years. All patients had significant mitral valve regurgitation, and the mean severity was 3.5 +/- 0.6. Prolapse of the posterior leaflet was diagnosed in 393 patients (84%), and prolapse of the anterior leaflet was diagnosed in 250 patients (53.4%). Mean left ventricular function was 64.8 +/- 12.3%. All patients were operated on with the minimally invasive approach via a right lateral mini-thoracotomy, femoral cannulation for cardiopulmonary bypass, and the transthoracic direct clamp technique. Mean duration of cardiopulmonary bypass was 136 +/- 40 minutes, and mean aortic clamp time was 87 +/- 31 minutes. Gore-Tex neochordae were used in 149 patients (32%) on both leaflets, in 224 patients (47.7%) on the posterior leaflet only, and in 95 patients (20.3%) on the anterior leaflet only. A mean number of 2.7 +/- 1 loops at a mean length of 21 +/- 3.3 mm were used on the A2 segment. On the P2 segment, a mean number of 3.2 +/- 1 loops at a mean length of 14.3 +/- 3.1 mm were applied. The intraoperative course was uneventful in all patients. Early reoperation for bleeding had to be performed in 18 patients (3.9%). Mean duration of hospital stay was 11.9 +/- 13 days. The 30-day mortality rate was 1.5% (7 patients), and 1-year mortality rate was 2.6% (12 patients). MVR with neochordae and the loop technique is an easy and effective treatment for degenerative mitral valve disease. The procedure is reliable and reproducible, leading to low morbidity and mortality. Thus, use of Gore-Tex neochordae has become the standard technique for MVR at our institution. PMID- 17870005 TI - Outcomes of mitral valve repair for mitral regurgitation due to degenerative disease. AB - The aim of this study was to review the clinical and echocardiographic outcomes after mitral valve repair for mitral regurgitation due to degenerative disease of the mitral valve. A total of 649 consecutive patients who had isolated mitral valve repair were prospectively followed up for 6.8 +/- 3.1 years. The mean age was 58 +/- 11 years. The operative mortality rate was 0.6%; the late mortality rate was 14.6%; and survival at 15 years was 67 +/- 5%. Age by increments of 5 years, advanced functional class, and impaired left ventricular function were independent predictors of late death. The freedom from reoperation on the mitral valve at 15 years was 92 +/- 3%, and the freedom from late, recurrent, severe mitral regurgitation was 85 +/- 4%. Most patients were in functional classes I or II at the latest follow-up contact. Mitral valve repair is associated with low operative mortality and morbidity, but it does not arrest the degenerative process. This study suggests that rates of reoperation underscore rates of late failure of the mitral valve repair. PMID- 17870006 TI - Adjunctive procedures in degenerative mitral valve repair: tricuspid valve and atrial fibrillation surgery. AB - Tricuspid regurgitation (TR) and atrial fibrillation (AF) are frequently encountered in patients with myxomatous mitral valve disease. Recent publications have indicated the seriousness of untreated TR, even in those with no TR but only annular dilation. If left untreated, the patients with annular dilation without TR were more prone to develop TR during follow-up and had worse New York Heart Association functional class. At the Bluhm Cardiovascular Institute, 39% of patients who had mitral valve surgery had a history of AF. This included 54.4% of patients who were undergoing a re-operation. Five randomized, prospective clinical trials have documented that patients with permanent AF who undergo mitral valve surgery are far more likely to return to sinus rhythm if AF is treated with ablation at the same time as the mitral valve operation. For the group of patients with permanent AF, sinus rhythm was restored in only 5% to 33% of patients in the control group versus 44% to 93% of those in whom ablation was applied. A variety of technologies are available to ablate AF. The basic lesion must electrically isolate the pulmonary veins. For patients with permanent AF, there is evidence that a connecting lesion to the mitral valve annulus will increase success and that biatrial lesion sets will provide the best long-term freedom from AF. PMID- 17870007 TI - Future directions in degenerative mitral valve repair. AB - Mitral valve repair is by far the most common operation for degenerative mitral regurgitation. If the procedure is performed before left ventricular dysfunction occurs and atrial fibrillation develops, the operative risk is very low and life expectancy is super imposable to that of the sex- and age-matched population. Despite these achievements, there are areas that could still be improved. Progress in treating degenerative mitral regurgitation is expected to move along several directions. More precise diagnostic methods will be developed to reliably quantify mitral regurgitation and identify early irreversible ventricular and atrial changes. The refinement of surgical techniques and search for new, innovative solutions should never be abandoned. Finally, transcatheter correction of mitral regurgitation represents a new, emerging field of cardiovascular medicine and is expected to have a significant impact on the surgical practice in the future. PMID- 17870009 TI - Frontiers in emphysema research. AB - Chronic obstructive pulmonary disease (COPD) is a complex inflammatory disease with a myriad of pulmonary and nonpulmonary disease manifestations. COPD is a heterogeneous disease consisting of emphysematous destruction, airway inflammation, remodeling, and obstruction. Once conceptualized as a unidimensional disease isolated to the lung, it is now recognized to have significant systemic manifestations, such as osteoporosis, cardiovascular disease, and skeletal muscle wasting. As the clinical phenotypic expressions of COPD become more precisely characterized, so does the pathogenesis of this disease. Great strides are now being made in our understanding of genetic susceptibility, airway inflammation, the immune response to cigarette smoke, and inflammatory biomarkers. This review will discuss the most recent progress on selected topics in COPD pathogenesis, inflammation, and genetics. With time, we hope to expand our current understanding to predict who will develop disease and who will not, and why some patients develop particular disease phenotypes. In addition, we hope to clarify the inflammatory mechanisms involved in order to develop novel therapies and identify disease biomarkers that will lead to better tools for monitoring disease activity. Finally, we hope to develop treatments aimed at lung regeneration and repair, to reverse lung damage that has already occurred. We are optimistic that novel therapies like gene therapy and advanced antiinflammatory agents will be in our future. Judging by the progress made in the last decade, these tools may soon become a reality. PMID- 17870010 TI - Medical therapy for chronic obstructive pulmonary disease in 2007. AB - Medical treatment for patients with stable chronic obstructive pulmonary disease (COPD) has evolved significantly over the past 2 decades. Current World Health Organization recommendations suggest a stepwise approach to therapy depending upon disease severity. As-needed use of short-acting bronchodilators is recommended for patients with mild disease. Scheduled dosing of bronchodilators is recommended for patients with more advanced disease. Inhaled beta-agonists and anti-cholinergic agents in combination have proved to be more effective than either agent alone. Long-acting preparations are associated with better disease control and have not been associated with tachyphylaxis. Inhaled corticosteroids are useful for reducing the frequency of exacerbations in patients who experience one or more episodes per year. Oxygen therapy is clearly beneficial in patients with advanced COPD and chronic respiratory failure, and its potential benefits in less severe disease are currently being studied. Pulmonary rehabilitation benefits patients with mild-to-severe disease, although the greatest benefits have been demonstrated in those with moderate COPD. New ultra-long-acting inhaled bronchodilators, phosphodiesterase inhibitors, protease inhibitors, and retinoids intended to promote tissue regeneration are currently being evaluated in clinical trials as future therapeutic agents. PMID- 17870011 TI - Optimizing the selection of surgical candidates for lung volume reduction surgery. AB - The optimal selection of patients for lung volume reduction surgery (LVRS) is currently based on empiric clinical findings. Patients who benefit from LVRS have the common characteristics of impaired quality of life associated with apical predominant pulmonary hyperinflation and airflow obstruction. Within this category, patients who do not benefit from LVRS appear to have small airways disease that can be detected by inspiratory resistance studies. In addition to appropriate emphysema physiology, the selection of patients for LVRS must consider medical comorbidities and perioperative risk factors. Based on findings of the National Emphysema Treatment Trial, most of the perioperative morbidity and mortality of LVRS is associated with cardiopulmonary risk that needs to be considered preoperatively. Finally, a preoperative conditioning program can provide an additional screening process to identify patients physically and emotionally prepared for surgery. PMID- 17870012 TI - Surgical interventions for emphysema. AB - Three surgical procedures are pertinent to the treatment of end-stage emphysema: giant bullectomy, lung volume reduction surgery (LVRS), and lung transplantation. Patients with localized disease manifesting as a giant bulla that compresses adjacent healthy lung tissues can be offered bullectomy. Patients with diffuse disease can be offered LVRS, lung transplantation, or staged LVRS/lung transplant, depending on multiple factors including age, lung function parameters, lobar predominance, and whether the disease is uni- or bilateral. Since end-stage emphysema is refractory to most medical treatment, surgery is often the only remaining option. PMID- 17870013 TI - Lessons from the national emphysema treatment trial. AB - Medicare coverage for lung volume reduction surgery has been approved recently by the Centers for Medicare and Medicaid Services for the treatment of severe emphysema. The scientific basis for this approval stems largely from findings of the National Emphysema Treatment Trial (NETT). The purpose of this article is to review the contributions of the NETT to the management of chronic obstructive pulmonary disease. PMID- 17870014 TI - Evolving endoscopic approaches for treatment of emphysema. AB - Novel endobronchial methods for reducing lung volume in patients with advanced emphysema are currently being evaluated in clinical trials as potential alternatives to lung volume reduction surgery (LVRS). Three bronchoscopic lung volume reduction (BLVR) approaches have shown promise in initial testing: (1) placement of endobronchial one-way valves to promote atelectasis by blocking inspiratory flow; (2) airway bypass tract formation using a radiofrequency catheter to facilitate emptying of damaged lung regions with long expiratory times; and (3) instillation of biological adhesives designed to collapse and remodel hyperinflated lung. The limited clinical data currently available suggests all three techniques are reasonably safe. However, efficacy signals have been smaller and less durable than those observed after LVRS. Studies to optimize patient selection, refine treatment strategies, characterize procedural safety, elucidate mechanisms of action, and characterize short- and longer-term effectiveness of each approach are ongoing. PMID- 17870015 TI - An update on plexiform fibrohistiocytic tumor and addition of 66 new cases from the Armed Forces Institute of Pathology, in honor of Franz M. Enzinger, MD. AB - The seminal article of Drs Franz Enzinger and Renyuan Zhang in 1988 defined plexiform fibrohistiocytic tumor (PFHT) as a distinctive entity. They described 65 cases (from 1965 to 1985) in children and young adults, with female and upper extremity predominance. These tumors were morphologically divided into 3 groups: fibroblastic, histiocytic (often with osteoclast-type giant cells), and mixed. Most tumors exhibited a plexiform and infiltrative arrangement of cells at the dermal/subcutaneous junction. Two fibroblastic PFHT had a metaplastic bone formation. Absence of cellular pleomorphism, low mitotic activity, dense hyalinization, hemorrhage, and chronic inflammation were observed. Vascular invasion was present in 1 recurrent, yet nonmetastatic, case. Tumors were negative for S100 protein, desmin, cytokeratin, factor VIIIrag, and lysozyme. Most patients were without disease up to 60 years after excision; 32 (37.5%) cases with follow-up recurred and 2 of those patients had regional lymph node metastasis at 9 and 36 months, respectively, yet there were no systemic metastases. In the interim, there have been additional studies on PFHT. We wanted to update the literature and add 66 new PFHT cases (1986-present) from the Armed Forces Institute of Pathology, since this seminal article, in honor of Dr Franz Enzinger. There were 37 men and 29 women; patient age ranged from 1 to 77 years (median, 20 years; 53% of patients were younger than 20 years). Twenty-eight cases occurred in the upper extremity (mostly forearm), 16 in lower extremity, 11 in trunk, 9 in head and neck, and 2 of unknown site. Although most cases were observed at the dermal/subcutaneous interface, 22 cases were predominantly dermal, and the rest predominantly subcutaneous, with 4 superficially involving skeletal muscle. Except for 12 predominantly dermal cases, most cases had an infiltrative growth pattern. Thirty-four cases were predominantly histiocytic, 16 predominantly fibroblastic, and the remaining 16 mixed. Two fibroblastic cases demonstrated the microfat cells (probably secondary to subcutis infiltration). All cases exhibited a plexiform growth pattern of small- to medium-sized nodules; 41 cases had giant cells, mainly osteoclast type, often the predominantly histiocytic type. The purely fibroblastic often had surrounding inflammation, 2 cases with marked inflammation. Perineural growth was observed in 5 cases, peri Pacinian corpuscle growth in 2 cases, adnexal trapping in several, and, increased hyalinized collagen in 17 cases. Eight cases demonstrated focal myxoid change. Only 1 case, a histiocytic, had bone formation. Although increased cytologic atypia and mitotic activity were noted in a few cases, an atypical mitosis was only observed in 1 case. No cases demonstrated vascular or lymphatic invasion or necrosis. The tumors were generally positive for CD68 and SMA, occasionally for MSA, and negative for keratin, desmin, HMB45, S100 protein, and CD34. Overall, the findings were very similar to the original observations made by Dr Enzinger and his colleague, with the minor exceptions of roughly equal sex distribution (possibly due to timely referral bias), and additional morphologic features of myxoid change, adnexal sparing, increased inflammation, and microfat similar to recently described lipofibromatosis. The relationship between PFHT and cellular neurothekeoma is also explored. PMID- 17870016 TI - Intraosseous lipoma. A clinical, radiologic, and pathologic study of 5 cases. AB - Intraosseous lipoma is an uncommon tumor of bone with indistinct radiologic features that makes it diagnostically challenging to radiologists and pathologists. There is a need to familiarize these physicians with the radiographic and pathologic features of this lesion for the correct diagnosis. We described the radiologic and pathologic features of intraosseous lipoma in 5 women. In 4 patients, the tumors occurred in long bones, whereas in the fifth patient, the skull was involved. Patients' age ranged from 50 to 63 years. Plain radiographs of the long bones revealed well-circumscribed benign-appearing osteolytic lesions with sclerotic margins, whereas in the skull, a poorly defined lytic aggressive-looking lesion was observed. In the long bones, the lesions showed remodeling of the affected bone with matrix calcification, simulating bone infarcts. Microscopically, mature adipose tissue with fat necrosis, absence of hematopoietic elements, and dystrophic calcification corresponding to the calcified matrix seen on the plain radiographs were seen. The osteolytic skull lesion had large caliber thin-walled vasculature with occasional fibrin thrombi mimicking intramuscular hemangiomas of soft tissue. On plain radiographs, an intraosseous lipoma is usually seen as a rather benign-appearing osteolytic bone lesion with well-defined margins and a heavily calcified/ossified dense matrix. Plain radiographs alone cannot establish the diagnosis of intraosseous lipoma as it mimics several other benign and malignant bone lesions. Intraosseous lipoma often contains calcified necrotic fat with little mature adipose tissue and characteristically induces expansion/remodeling of the affected bone. PMID- 17870017 TI - Epidermal growth factor receptor is not amplified in schwannomas. AB - Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor of the ErbB family. This family of receptors plays an active role in cellular growth and mitogenesis. It is well established that the overexpression of ErbB receptors in human cancers, most commonly because of true genomic amplification, correlates with a more aggressive clinical course. There is limited data published on the expression and amplification of EGFR in schwannomas. Both neurofibromas and schwannomas are capable of progression to malignant peripheral nerve sheath tumors (MPNSTs). A subset of human MPNSTs, both NF-1-related and sporadic, overexpress EGFR via true genomic amplification of the short arm of chromosome 7 (7p12). The goal of this study is to assess whether EGFR is expressed and/or amplified in human schwannomas. Twenty schwannomas in 12 women and 8 men (mean age, 51 years) were analyzed for EGFR expression via immunohistochemistry and fluorescence in situ hybridization. None of the 20 cases were positive for EGFR expression via immunohistochemistry; 3 tumors showed focal nonspecific Golgi staining. None of the cases demonstrated true genomic amplification of the EGFR region via fluorescence in situ hybridization. The mitogenic signaling for schwannomas is unlikely to be related to overexpression or amplification of EGFR; however, acquiring this signaling pathway might contribute to the progression of a subset of benign peripheral nerve sheath tumors to MPNST. PMID- 17870018 TI - Cysticercosis in the elderly. AB - The immunosenescence, a peculiarity of the aging process, increases the susceptibility of elderly individuals to neoplasia, infections, and parasitosis, among them, cysticercosis. The aim of this study was to compare the epidemiological and anatomopathological characteristics of cysticercosis in elderly or nonelderly patients. We reviewed 72 autopsies, protocols and specimens, performed in the School Hospital of the Triangulo Mineiro Federal University. We selected 3 groups: elderly with cysticercosis, nonelderly with cysticercosis, and control group without cysticercosis. From the patients with cysticercosis, 27.8% were elderly. Of these, 80% presented with neurocysticercosis and 20% cardiac cysticercosis. In the elderly, the early stages of the parasitic development, vesicular and colloidal vesicular, prevailed (75%). In relationship with the causes of death, death in 40% of the elderly was by neoplasic and 35% by cardiovascular, whereas for the nonelderly, death in 63.5% was by cardiovascular and 25% by infectious. There was a significant difference between groups with relation to neoplasic and cardiovascular causes. Therefore, cysticercosis was frequent in elderly patients, and probably patients are continuously infected with cysticercosis as they age. Perhaps, decurrence of the immunosenescence associated with immunological alterations caused by cysticercosis form favorable conditions to the development of neoplasias in the elderly attacked by the parasitosis. PMID- 17870019 TI - Histology safety: now and then. AB - Histology safety usually focuses on general laboratory issues, but this article concentrates on the hazards affecting the individual histotech and their evolution in the last half a century. Using the information from a survey especially designed for the occasion, the hazards were divided into 4 groups, and their prevalence was expressed as percentages for national and foreign laboratories. All the laboratories received a "safety index" (SI) with an average value of 0.77 +/- 0.11 for 63 national laboratories and 0.69 +/- 0.13 for 22 foreign laboratories, these 2 averages being statistically different (P < .02). The historical evolution of the SI required answering the same questionnaire retrospectively, and so it was done for 17 laboratories with an SI average of 0.27 +/- 0.12 for 1955/1989 and 0.77 +/- 0.13, almost 3 times larger for 1990/2007, with improvement of all safety issues. The technological, organizational, and regulatory advances before 1989 showed an unremarkable effect on the SI, and the only circumstance considered as the driving force behind the almost triple increment of the SI during 1990/2007 was the awareness that the AIDS epidemic instilled in the minds and consciences of the medical laboratory personnel in general. Even after almost tripling the average SI value in 2007, national histology laboratories obtained a grade average of "C+" only, leaving room for improvement. PMID- 17870020 TI - Pleomorphic myofibrosarcoma of the tibia with aneuploid DNA content. AB - Myofibrosarcomas of the tibia are exceedingly rare, with only one case reported in the literature. We describe DNA ploidy of high-grade myofibrosarcoma of the tibia in correlation with clinicomorphologic and ultrastructural features in a 16 year-old adolescent girl. Radiological studies revealed an expanding osteolytic bone lesion in the metaphysis of proximal tibia. A biopsy was consistent with malignant fibrous histiocytoma. The final diagnosis of myofibrosarcoma was supported by light microscopy and corroborated by electron microscopy and immunohistochemistry findings. The DNA content analysis showed an aneuploid tumor. She developed local recurrence at 6 months after initial treatment with no evidence of lung metastases and 16 months later is alive with persistence of disease. This is the second case reported in the literature with this location. In this case, the high grade correlated with recurrence behavior and aneuploidy DNA content but not with metastases. By ultrastructural analyses, fibronexus and intracellular collagen persisted in high-grade myofibrosarcoma. PMID- 17870021 TI - Giant cell tumor of soft tissue arising in breast. AB - Primary giant cell tumor of soft tissue (GCT-ST) arising in breast is exceedingly rare. We report a case of a 60-year-old woman with a primary breast giant cell tumor that appeared histologically identical to giant cell tumor of bone and had a clinically malignant course. The patient presented with a cystic mass of the breast, suspected on imaging to be an organizing hematoma, possibly related to previous injury. Histopathological evaluation revealed a neoplasm composed of mononuclear cells admixed with osteoclast-like giant cells resembling giant cell tumor of bone. Immunohistochemical staining was positive for CD68, smooth muscle actin, and vimentin, but was negative for a panel of epithelial and additional muscle markers. These features were most consistent with GCT-ST, an uncommon neoplasm of low malignant potential. Despite aggressive surgical treatment achieving clear surgical margins, the patient expired with pulmonary metastases within a year of her initial presentation. This case demonstrates the difficulty of predicting clinical behavior of GCT-ST of breast on the basis of histological features and depth of tumor alone. To our knowledge, this is the first case report of a GCT-ST arising in the breast associated with a fatal outcome. The distinction of this entity from other more common primary breast tumors with giant cell morphology is also emphasized. PMID- 17870022 TI - Intestinal anisakidosis (anisakiosis). AB - A case of intestinal anisakidosis in a 42-year-old man in Japan is presented. His chief complaint was an acute onset of severe abdominal pain. Approximately 12 hours before the onset of this symptom, he had eaten sliced raw mackerel ("sashimi"). Upper endoscopy was unremarkable. At exploratory laparotomy, an edematous, diffusely thickened segment of jejunum was observed, which was resected. The postoperative course was uneventful. The segment of small intestine showed a granular indurated area on the mucosal surface, and microscopically, a helminthic larva penetrating the intestinal wall, which was surrounded by a cuff of numerous neutrophils and eosinophils, as well as diffuse acute serositis. A cross section of the larva revealed the internal structures, pathognomonic of Anisakis simplex. Although anisakidosis is rare in the United States, with the increasing popularity of Japanese cuisine, the incidence is expected to increase, and pathologists should be familiar with this disease. PMID- 17870023 TI - Syphilitic tonsillitis presenting as an ulcerated tonsillar tumor with ipsilateral lymphadenopathy. AB - We describe a 49-year-old man who presented with a cervical mass of a week's evolution, which clinically mimicked a tumoral expansion. Physical examination showed a left cervical mass of 6 x 4 x 2 cm, associated to a left ulcerated tonsillar tumor. The presumptive diagnosis was a tonsillar cancer with lymph node involvement. An amygdalectomy and a frozen section biopsy of the cervical tumor were performed. The biopsy displayed a reactive lymphadenopathy with follicular and interfollicular hyperplasia rich in plasma cells, epithelioid areas, and an outstanding parcel fibrosis of subcapsular, interfollicular, and perifollicular distribution associated to an isolated focus of polymorphonuclear leukocytes and obliterative parietal angiovascular proliferation. The tonsil presented a similar but ulcerated process. These results suggested an infectious reactive process, probably luetic. A Warthin-Starry stain revealed spirochetes in the tonsillar ulcer. Laboratory examinations revealed a positive VDRL test and negative serology for HIV. In conclusion, a primary syphilis of the oropharyngeal tonsil with a syphilic lymphadenopathy was diagnosed. The literature about tonsillar syphilis is reviewed. PMID- 17870024 TI - True thymic hyperplasia associated with severe thymic cyst bleeding in a newborn: case report and review of the literature. AB - We report on a 5-week-old male infant with recurrent respiratory distress since birth and congenital thymic hyperplasia. Acute life-threatening thymic bleeding apparently from ruptured thymic cysts into the pleural spaces complicated the clinical situation. Thoracotomy and complete thymectomy were performed. Histologic examination revealed normal thymic architecture with cysts of different sizes and an increased thymic weight of 30 g. The combination of true thymic hyperplasia and cyst bleeding in a newborn has not been previously reported and will be discussed in relation to the available literature on respiratory distress due to thymic pathology in childhood. PMID- 17870025 TI - Pathology of chronic lymphocytic leukemia: an update. AB - Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) is a clonal lymphoproliferative disorder characterized by proliferation of morphologically and immunophenotypically mature lymphocytes. CLL/SLL may proceed through different phases: an early phase in which tumor cells are predominantly small in size, with a low proliferation rate and prolonged cell survival, and a transformation phase with the frequent occurrence of extramedullary proliferation and an increase in large, immature cells. Although some patients with CLL have an indolent disease course and die after many years of unrelated causes, others have very rapidly disease progression and die of the disease within a few years of the diagnosis. In the past few years, considerable progress has been made in our ability to diagnose and classify CLL accurately. Through cytogenetics and molecular biology, it has been shown that CLL and variants are associated with a unique genotypic profile and that these genetic lesions often have a direct bearing on the pathogenesis and prognosis of the disease. Similarly, the development of antibodies to new biologic markers has allowed the identification of a unique immunophenotypic profile for CLL and variants. Moreover, accumulating evidence suggests that CLL cells respond to selected microenvironmental signals and that this confers a growth advantage and an extended survival to CLL cells. In this article, we will review the progress in the pathobiology of CLL and give an update on prognostic markers and tools in current pathology practice for risk stratification of CLL. PMID- 17870028 TI - Preface. Established rheumatoid arthritis. PMID- 17870027 TI - Re: adenolipomas of the head and neck: analysis of 6 cases. PMID- 17870029 TI - Established rheumatoid arthritis: clinical assessments. AB - Clinical assessment of established rheumatoid arthritis (RA) can have several purposes. It can be used to evaluate prognosis, disease course or interventions at both the individual and the group level (i.e. in a clinical trial), over the short or long term. The instruments used for the different purposes are not always the same. For example, information on prognosis is very useful when assessing the risk:benefit ratio of early aggressive pharmacotherapy; however, established prognostic factors are currently of limited use in individual patients with established RA. As, at the individual patient level, disease activity, disability and joint damage have variable courses, the course of the disease should be evaluated regularly both with process (i.e. erythrocyte sedimentation rate, joint counts) and with outcome (i.e. radiological progression, sum of past process) measures. For the evaluation of interventions, 'core sets' of valid measures to assess disease activity, outcome and specific criteria for improvement are used; these can, to some extent, be useful in clinical practice. PMID- 17870030 TI - Measuring disability and quality of life in established rheumatoid arthritis. AB - Rheumatoid arthritis is a chronic inflammatory disease with a major impact on physical and psychological health. It can cause severe disability and reduce health-related quality of life, aspects that are important to patients. Thus, it is important to measure disability and health-related quality of life in clinical practice and in clinical trials. This article presents an overview of the most important measures of outcome concerning disability and health-related quality of life, including different forms of the Health Assessment Questionnaire (HAQ, MHAQ, MDHAQ, HAQ II), visual analogue scales for fatigue and function, SF-36, Arthritis Impact Measurement Scales (AIMS/AIMS2), the Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire, Nottingham Health Profile, Sickness Impact Profile and the utility instruments 15D, EQ-5D, SF-6D and Health Utilities Index (HUI) 2 and 3. PMID- 17870031 TI - Established rheumatoid arthritis - new imaging modalities. AB - New imaging modalities are assuming an increasingly important role in the investigation and management of rheumatoid arthritis. It is now possible to obtain information about all tissues within the joint in three dimensions using tomographic techniques such as magnetic resonance imaging (MRI) and high resolution computerized tomography. Erosions are very clearly depicted using these modalities and MRI also allows imaging of soft tissues with assessment of joint inflammation. High-resolution ultrasound is a convenient clinical technique for the assessment of erosions, synovitis and tenosynovitis in real-time and facilitates diagnostic and therapeutic interventions such as joint aspiration and injection. Exciting experimental modalities are also being developed with the potential to provide not just morphological but functional imaging. Techniques such as positron emission tomography (PET) and single photon emission tomography (SPECT) can reveal actively metabolizing bone and the proliferation of synovial cells via radioactive labeling. Bioluminescence and fluorescence reflectance imaging are other approaches that allow imaging, and potentially the delivery of therapeutic agents, at a molecular level. PMID- 17870032 TI - Qualitative assessments. AB - Current NHS policies emphasise the involvement of patients and place them centre stage in the evaluation of health care. The unique experiences and views that patients can bring to health service research can be understood as complementary to staff skills. Qualitative research methods in particular provide a distinctive approach to recording and interpreting patients' perceptions and opinions; these insights can be used when developing and evaluating new treatments and services. PMID- 17870033 TI - Mortality in established rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is associated with reduced life expectancy. Whether the development of RA initiates this process of premature ageing or is part of it is not clear. The excess mortality is apparent within the first few years of disease and increases with RA disease duration. Most of the excess deaths are attributable to infection, cardiovascular disease (in particular coronary heart disease) and respiratory disease. Deaths due to lung cancer and non-Hodgkin's lymphoma, but not other cancers, are also increased. There is some evidence that effective disease-modifying therapy can improve survival but, overall, survival in RA patients has not improved to the same degree as in the general population over recent decades. PMID- 17870034 TI - Comorbidities in rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is often characterized by the burden of swollen joints, pain, and decreased physical function, but less understood are the many manifestations of additional health conditions that are associated with RA and its treatments. First brought to light with observations of increased mortality in RA, studies noted the increased rates of cardiovascular and infection events. The chronic, debilitating, autoimmune nature of RA affects the patient directly or indirectly in almost all organ systems, from cardiovascular problems and infections to depression and gastrointestinal ulcers. On average, the established RA patient has two or more comorbid conditions. It should be the responsibility of the rheumatologist to take these and the risk of additional conditions into account when treating the patient. This chapter reviews important comorbidities in patients with RA, their prevalence, and their relation to RA. PMID- 17870035 TI - Extra-articular manifestations and complications of rheumatoid arthritis. AB - Rheumatoid arthritis (RA) is a systemic inflammatory disease that can involve other tissues and organs as well as synovial joints. This chapter reviews the clinical aspects of extra-articular RA, from the early descriptions in rheumatology texts to reports from more recent cross-sectional and inception cohort studies. There is no agreed classification for these manifestations and, because criteria and definitions vary so much, this report includes not only the classic extra-articular features but also the non-articular complications of RA, for example normochromic normocytic anaemia and chronic leg ulcers, and the important disease-associated comorbidities, including non-Hodgkin's lymphoma, ischaemic heart disease and osteoporosis. Incidence and frequency figures for extra-articular RA vary according to study design. Nodules are the most common extra-articular feature, and are present in up to 30%; many of the other classic features occur in 1% or less in normal clinic settings. Sjogren's syndrome, anaemia of chronic disease and pulmonary manifestations are relatively common - in 6-10% - are frequently present in early disease and are all related to worse outcomes measures of rheumatoid disease, in particular functional impairment and mortality. Currently, there are no reliable predictors for these features in early RA, although they are associated with men, smokers, more severe joint disease, worse function, high levels of inflammatory markers, and the presence of rheumatoid factor (RF), antinuclear antibodies (ANA) and the RA HLA-related shared epitope. Many of these manifestations are related to the more active and severe RA, so early and more aggressive RA drug therapies are being employed and, although evidence from randomised studies is not available, this approach would seem appropriate in view of the adverse effect of extra-articular manifestations on RA outcomes. Unfortunately, specific therapies for extra-articular manifestations of RA are largely disappointing or unavailable, except for steroids and cyclophosphamide for vasculitis. The place for biological therapies is still not clear. Pulmonary fibrosis in RA has a poor prognosis whether treated with large doses of steroids, cytotoxic or disease modifying drugs like cyclosporine, or biologics. In summary, extra-articular features and non articular complications of RA are common and are generally related to worse disease. They need to be recognised early and managed promptly. PMID- 17870036 TI - Economic consequences of established rheumatoid arthritis and its treatment. AB - Recent years have witnessed tremendous progress in the therapeutic approach to rheumatoid arthritis (RA). The introduction of novel biologic agents, in particular TNF inhibitors, has allowed clinicians to achieve improved outcomes for their patients. An important factor that has affected the utilization of novel therapies is their acquisition costs, which far exceed those for older antirheumatic drugs. Nevertheless, RA is a serious chronic condition which can cause substantial morbidity and even accelerated mortality for affected individuals. The notable sequelae of uncontrolled rheumatoid synovitis include joint damage and functional disability, which in turn, cause severe economic consequences not only to patients and their families, but also to society. Therefore, it is appropriate for pharmacoceconomic analyses to take into account all relevant costs, not only of the treatments, but of the disease itself. In this way, the value of therapies can be correctly estimated. PMID- 17870037 TI - The course of established rheumatoid arthritis. AB - Rheumatoid arthritis (RA) varies over time in individual patients and there are marked differences between patients in its impact and progression. The course of RA is therefore unique to each individual patient and is affected by the overall pattern of disease; many patients have classical polyarticular disease but there is also a range of subtypes, such as fibromyalgic and polymyalgic disease. Some patients with RA enter a period of sustained remission; this varies between 10% and 36% of cases; its frequency is mainly influenced by the different approaches to studying RA patients over time, and does not represent a true difference in disease outcome. Most patients have persisting synovial inflammation and disease activity scores average between 3 and 4; there is some evidence that inflammation is less marked in late RA. Persisting synovitis results in increasing disability this worsens by an average of 0.6% each year - and in joint damage, which increases by an average of 2% each year. Comorbidities and extra-articular features are commonplace: about one-third of patients, respectively, have associated cardiovascular disease, lung disease or extra-articular features, although severe extra-articular problems like vasculitis affect only about 10% of patients. Some aspects of the course of RA are influenced by genetic risks; currently these are only weak predictors but it is anticipated their value will increase with time. PMID- 17870038 TI - Calcium supplementation and weight bearing physical activity--do they have a combined effect on the bone density of pre-pubertal children? AB - The adaptation of bone to exercise has been shown to be modified by dietary calcium intake. The aim of this randomised controlled trial was to investigate whether there was a differential response to calcium supplementation in elite gymnasts and school children controls. The primary hypothesis was that gymnasts who took calcium supplements would have greater increases in cortical and trabecular volumetric bone mineral density (vBMD) at the radius and tibia. Secondary outcomes studied were changes in bone geometry at the radius and tibia and lumbar spine and whole body measurements. Children were randomised to 12 months daily supplementation of 500 mg elemental calcium (1250 mg (in the form of calcium carbonate salt)) or placebo. Outcome measures were assessed using peripheral quantitative computed tomography (pQCT) (distal and diaphyseal radius and tibia) and dual energy X-ray absorptiometry (DXA) (lumbar spine and whole body). Eighty-six subjects participated in the trial (44 gymnasts, 42 controls) and 75 subjects completed the trial (39 gymnasts, 36 controls). Data were analysed by analysis of covariance adjusting for baseline value of bone parameters, age, height, gender and puberty, and delay between baseline measurement and start of intervention. The primary analysis was for a calcium exercise interaction; a pooled calcium effect with no interaction was also tested. Results are presented as ratios (95% confidence intervals). At the distal tibia, trabecular vBMD showed a significant interaction (p=0.04), with controls (1.00: 0.99, 1.09) responding more than gymnasts (0.98: 0.94, 1.02) to supplementation. At the distal radius, change in trabecular vBMD was not significant (p=0.05). There were no differences in change in cortical vBMD at either site between the gymnasts and controls (tibia: p=0.82, radius: p=0.88). For all other secondary outcomes at radius, tibia, spine and whole body no significant interactions were found. In conclusion, there was no beneficial effect of additional calcium in gymnasts who already consume their recommended nutrient intake (888 mg/day; United Kingdom reference nutrient intake for 8- to 11-year-olds is 555-800 mg/day) for calcium. We speculate that gymnasts have already adapted their bones (geometry and vBMD) to the demands imposed upon them by the loading they are subjected to during gymnastics and do not benefit from additional calcium supplementation. PMID- 17870039 TI - Discordance of longitudinal changes in bone density between densitometers. AB - This study examined the concordance in BMD measurement and longitudinal change in BMD between the GE Lunar Prodigy and GE Lunar DPX. Even though a high concordance between the densitometers was observed on a single measurement occasion, a significant discordance in longitudinal changes in BMD was observed. INTRODUCTION: Measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) technology plays an important role in the diagnosis and management of osteoporosis. The present study examined the concordance in BMD measurement and longitudinal change in BMD between GE Lunar Prodigy and DPX. METHODS: BMD at the lumbar spine and femoral neck was measured in 135 individuals (47 men and 88 women, mean age 73+/-9 years) using both GE Lunar DPX and Prodigy densitometers at baseline. In this group, 56 individuals (22 men and 34 women) had repeated BMD measurements using the DPX and Prodigy during a subsequent follow-up visit (average duration: 2.2 years). RESULTS: For a single BMD measurement, the coefficient of concordance between the Prodigy and DPX was greater than 0.98 at the lumbar spine and 0.96 at the femoral neck, with the slope of linear regression being approximately 1.0. During the period of follow up, the lumbar spine BMD decreased by -0.5% (S.D. 1.8%) when measured by DPX, which was significantly different (p=0.002) from the change measured by Prodigy (mean change=0, S.D. 2.0%). However, there was no significant difference (p=0.95) in the rate of change in femoral neck BMD measured by DPX (mean=-1.6%, S.D.=2.9) and Prodigy (mean=-1%, S.D.=1.8%). The correlation in rates of BMD change between Prodigy and DPX was 0.63 at the lumbar spine and 0.52 at the femoral neck. Simulation analysis showed that the theoretical maximum correlation in rates of BMD change between Prodigy and DPX was 0.71. CONCLUSIONS: Despite both densitometers being highly concordant in a single BMD measurement, discordance in the assessment of BMD changes between the Prodigy and DPX densitometers was observed. These findings have implications regarding the assessment of response to therapy in a multi-centre setting when different densitometers are used. PMID- 17870040 TI - Language integration in bilingual sentence production. AB - To what extent are processes used in sentence production integrated between the different languages of a bilingual and to what extent are they kept separate? We consider three models that differ in their assumptions about the degree of integration: De Bot's [De Bot, K. (1992). A bilingual production model: Levelt's Speaking model adapted. Applied Linguistics, 13, 1-24] bilingual blueprint of the speaker, Ullman's [Ullman, M. T. (2001). The neural basis of lexicon and grammar in first and second language: The declarative/procedural model. Bilingualism: Language and Cognition, 4, 105-122] declarative/procedural model of bilingualism, and Hartsuiker et al.'s [Hartsuiker, R. J., Pickering, M. J., & Veltkamp, E. (2004). Is syntax separate or shared between languages? Cross-linguistic syntactic priming in Spanish/English bilinguals. Psychological Science, 15, 409 414] integrated model. A review of the evidence from bilingual sentence production studies shows that Hartsuiker et al.'s predictions are supported, but argues against the other two models. We discuss some repercussions for bilingual language use. PMID- 17870041 TI - Development of a real-time PCR assay for the diagnosis of scrub typhus cases in India and evidence of the prevalence of new genotype of O. tsutsugamushi. AB - A qualitative syber green real-time PCR with primers designed for a truncated portion of the 56kDa major outer membrane antigen gene of Orientia tsutsugamushi was used to diagnose scrub typhus from the blood or serum of suspected patients. Sixty-six blood and/or sera samples from fever cases, either with high index of suspicion for scrub typhus and/or positive by Weil-Felix test (> or = 1:160), were tested with the PCR. Specificity of the PCR was confirmed by end point melt curve analysis and sequencing of the amplicons. A nested PCR for determination of the serotypes of O. tsutsugamushi was performed on to the samples. In real-time PCR strong positive fluorescence was obtained in 73% of the suspected samples. Serotype-specific PCR amplification of some of the positive samples was indicative of the Kuroki type whereas the rest were non-responsive to this test. Sequence analyses of PCR amplicons indicated the presence of new, previously undescribed type of O. tsutsugamushi in this region. This one-step real-time PCR can be used for the detection and confirmation of scrub typhus, when used independently or in conjunction with, the Weil-Felix test, which is still the only available detection test for scrub typhus in most parts of the developing world. Elaborate studies need to be taken up to further evaluate its suitability as specific molecular tool for the diagnosis of scrub typhus and to delineate the prevalent strain types in these regions for a clear epidemiological understanding of this emerging infectious disease. PMID- 17870042 TI - Template-based synthesis of nanorod, nanowire, and nanotube arrays. AB - This review introduces and summarizes the fundamentals and various technical approaches developed for the template-based synthesis of nanorod, nanowire and nanotube arrays. After a brief introduction to various concepts for the growth of nanorods, nanowires and nanobelts, attention will be focused mainly on the most widely used and well established techniques for the template-based growth of nanorod arrays: electrochemical deposition, electrophoretic deposition, filling of templates by capillary force and centrifugation, and chemical conversion. In each section, relevant fundamentals will be first introduced, followed with examples to illustrate the specific details of each technique. PMID- 17870043 TI - The increasing racial disparity in infant mortality rates: composition and contributors to recent US trends. AB - OBJECTIVES: We examined trends in birthweight-gestational age distributions and related infant mortality for African American and white women and calculated the estimated excess annual number of African American infant deaths. STUDY DESIGN: Live births to US-resident mothers with a maternal race of white or African American were selected from the National Center for Health Statistics' linked live birth-infant death cohort files (1985-1988 and 1995-2000). RESULTS: The racial disparity in infant mortality widened despite an increasing rate of white low-birthweight infants. White preterm infants had relatively greater gains in survival and the white advantage in survival at term increased. Annually, African American women experience approximately 3300 more infant deaths than would be expected. CONCLUSION: The increasing US racial disparity in infant mortality is largely influenced by changes in birthweight-gestational age-specific mortality, rather than the birthweight-gestational age distribution. Improvement in the survival of white preterm and low-birthweight infants, probably reflecting advances in and changing access to medical technology, contributed appreciably to this trend. PMID- 17870044 TI - Pediatric traumatic macular hole: results of autologous plasmin enzyme-assisted vitrectomy. AB - PURPOSE: To review our experience with plasmin-assisted vitrectomy surgery for the treatment of pediatric macular holes. DESIGN: Retrospective, interventional case series. METHODS: Thirteen pediatric patients aged one to 15 years with a traumatic macular hole underwent surgical repair. All patients underwent surgery between February 1997 and March 2005 with autologous plasmin enzyme-assisted vitrectomy. After induction of posterior vitreous detachment (PVD), vitrectomy with membrane peeling and gas or silicone oil injection were performed followed by prone positioning for seven days. Main outcome measures included anatomic closure rate, visual outcome, and ocular complications. RESULTS: The macular hole was closed successfully in 12 (92%) of 13 cases. Of the 12 patients for whom vision could be measured, 11 patients (92%) had visual acuity improvement of 2 or more lines and six patients (50%) achieved vision of 20/50 or better; all of the patients achieved vision better than 20/200. The visual improvement was statistically significant (P = .005, Wilcoxon signed-rank test). Surgical complications included cataract formation in one patient and retinal detachment in one patient. CONCLUSIONS: Autologous plasmin enzyme may be a helpful adjunct when performing vitrectomy for traumatic macular holes. PMID- 17870045 TI - Phacoemulsification of cataract in patients receiving Coumadin therapy: ocular and hematologic risk assessment. AB - PURPOSE: To assess the risks of intra- and postoperative bleeding tendency associated with uncomplicated cataract surgery by phacoemulsification in patients receiving Coumadin treatment. DESIGN: Prospective, nonrandomized, interventional, consecutive case series. METHODS: Sixty-three consecutive patients underwent cataract extraction with lens implantation in 75 eyes. All patients were receiving Coumadin therapy at the time of surgery, and nine patients (14.3%) were also taking antiaggregants. The operations were performed by phacoemulsification technique under topical anesthesia. All patients underwent a hemostatic work-up before intervention. Structured questionnaires were completed by the surgeon immediately after the operation. In 18 (24%) eyes, the surgery was videotaped, and the tapes were reviewed subsequently for any bleedings by an independent observer. RESULTS: Twelve patients (19%) underwent surgery in both eyes, not simultaneously. The mean prothrombin time international normalized ratio (INR) was 2.03 at the time of the surgery. No significant intraoperative bleeding occurred. Four (6.3%) patients had minor postoperative ocular bleeding. A microscopic hyphema and a dot retinal hemorrhage were each seen in one eye on the first postoperative day, and small iris hemorrhages were identified in two additional eyes at the one-week visit. All bleedings disappeared within one week without affecting the visual acuity. The mean INR of the four patients with minor bleedings was 2.1. CONCLUSIONS: Cataract surgery by phacoemulsification in uncomplicated eyes can be performed safely in patients receiving Coumadin treatment. However, a large clinical trial is required to assess the safety of continuous Coumadin treatment associated with phacoemulsification in eyes with complicated cataract. PMID- 17870046 TI - Effect on intraocular pressure of extraocular muscle surgery for thyroid associated ophthalmopathy. AB - PURPOSE: To study the effect of extraocular muscle surgery on intraocular pressure (IOP) in patients with thyroid-associated ophthalmopathy. DESIGN: Retrospective, observational case series. METHODS: The medical records of patients with restrictive myopathy secondary to thyroid-associated ophthalmopathy who underwent strabismus surgery from July 1, 1997 through July 31, 2003 were reviewed and analyzed retrospectively. Seventeen patients met the criteria and were included in this study. All patients were seen at the Thyroid Eye Center at the University of California, San Diego, a university-based tertiary referral center. The main outcome measure was IOP readings obtained before and after surgery in both primary gaze and upgaze. RESULTS: A statistically significant decrease in IOP in upgaze was noted after extraocular muscle recession. The mean IOP before surgery was 16.6 +/- 3.78 mm Hg in primary gaze and 23.2 +/- 7.27 mm Hg in upgaze. After strabismus surgery, the mean IOP after one month was 15.7 +/- 2.36 mm Hg (P = .215) in primary gaze and 18.9 +/- 2.96 mm Hg in upgaze (P = .001). CONCLUSIONS: Strabismus surgery resulted in a significant reduction in IOP in the early postoperative period in patients with restrictive myopathy secondary to thyroid-associated ophthalmopathy. PMID- 17870047 TI - Hepatitis C and ocular surface disease. AB - PURPOSE: To assess the frequency of changes in the ocular surface and the presence of hepatitis C virus (HCV) in tear samples of patients with chronic HCV infection. DESIGN: Prospective, nonrandomized, clinical, interdisciplinary, single-center study. METHODS: Seventy-one patients with previously untreated chronic HCV infection and a control group consisting of 66 patients without systemic HCV infection were enrolled in the trial. The patients with HCV infection were screened for ocular symptoms, visual acuity, and ocular changes. Tear production was measured by the Jones test. Conjunctival impression cytologic analysis was performed. The presence of HCV ribonucleic acid (RNA) in tear and blood samples was determined by quantitative polymerase chain reaction. RESULTS: On examination, systemic HCV infection was present for a median of 30 months. Fifty percent of all HCV patients showed a decrease in tear production measured by the Jones test. Apart from epithelial changes related to dry eye syndrome in 12 patients, two patients presented mild peripheral corneal thinning. Polymerase chain reaction analysis detected HCV RNA in five (10%) of 52 tear samples. HCV RNA levels in tear samples (mean, 1.0 x 10(4) copies/ml) were considerably lower than in blood samples (mean, 5.3 x 10(5) copies/ml). CONCLUSIONS: Dry eye syndrome is the most frequently observed ocular feature in HCV infection. Patients with HCV infection (age range, 21 to 60 years) compared with the controls had a significant lower tear production (P = .05). The presence of HCV RNA in 10% of tear samples emphasizes the potential risk of viral transmission through tears. PMID- 17870048 TI - Silicone intubation with or without balloon dacryocystoplasty in acquired partial nasolacrimal duct obstruction. AB - PURPOSE: To examine if the addition of (antegrade) balloon dacryocystoplasty to bicanalicular silicone intubation affects the success rate in adults with incomplete nasolacrimal duct (NLD) obstruction. DESIGN: Prospective, randomized trial. METHODS: Seventy eyes of 70 patients with incomplete NLD obstruction and severe epiphora (Munk score grade 3 or 4) were treated randomly with dacryocystoplasty (Lacricath) and silicone intubation (Ritleng; n = 35, group 1; mean age, 54.4 years; standard deviation [SD], 11.8 years) or silicone intubation alone (n = 35, group 2; mean age, 53.5 years; SD, 13.1 years; P > .05). The silicone tubes were removed after, on average, three months. At the visit, we assessed the grade of epiphora using the Munk score. Complete success was defined as Munk score of 0 or 1, partial success was defined as Munk score of 2, and failure was defined as Munk score of 3 or 4. Long-term Munk scores were obtained through a telephone survey nine to 76 months after surgery (mean, 43.4 in group 1 and 34.9 in group 2; P > .05). RESULTS: Complete success was reported by 18 patients (52%) in group 1 and by 20 patients (57%) in group 2. Partial success was reported by one patient in group 1 and by one patient in group 2. No improvement was reported by 15 patients (44%) in group 1 and by 14 patients (40%) in group 2. Differences between the two groups proved to be not significant (P = .8, exact Chi-square trend test). CONCLUSIONS: In our patients with acquired partial NLD obstruction, treatment with a combination of antegrade dacryocystoplasty and silicone intubation was not associated with a higher success rate compared with treatment with silicone intubation alone. PMID- 17870049 TI - Affinity-based chemical proteomic probe for dehydrogenases: fluorescence and visible binding assays in gels. AB - A catechol rhodanine (CR)-based privileged scaffold, tailored to dehydrogenase enzymes, has recently been reported. This scaffold was used as a template in a focused combinatorial library, designed using the NMR SOLVE methodology, to prepare potent (50-200nM) biligand inhibitors for multiple dehydrogenases. It is reported here that this CR scaffold is also a fluorescent and visible probe for solution and in-gel (native) binding assays, making it a useful screening reagent for dehydrogenases, with applications as an affinity-based chemical proteomic probe. Initial application of this fluorescent CR probe was to dihydrodipicolinate reductase, an anti-infective drug target. The probe also shows in-gel binding affinity to two lactate dehydrogenase isozymes and to 1 deoxy-d-xylulose-5-phosphate reductoisomerase, making it a generally useful in gel staining reagent for multiple dehydrogenases. Because binding is noncovalent, such a reagent could be used in a displacement assay performed in a native gel, monitoring decrease in fluorescent band intensity. But, because the probe has the added function of serving as a privileged scaffold for dehydrogenase-targeted combinatorial libraries, it could also be used in a direct binding assay to screen for the highest-affinity biligand inhibitors that contain the fluorescent CR. Finally, the CR probe could be used as a stain in proteomic studies, to profile mixtures of proteins run on a native gel, to identify proteins that are likely to be dehydrogenases. PMID- 17870050 TI - Dietary flavonoid apigenin is a potential inducer of intracellular oxidative stress: the role in the interruptive apoptotic signal. AB - Apigenin is a representative dietary flavone (2-phenyl-4H-1-benzopyran-4-one) inhibiting cancer cell growth both in cell culture systems and in vivo. The prooxidant potential of apigenin was confirmed by the observations using flowcytometric and immunoblotting techniques that the intracellular accumulations of reactive oxygen species (ROS) and protein carbonyls were detected in the cells treated with apigenin in a dose-dependent manner. Conversely, chrysin (5,7 dihydroxyflavone) did not show any prooxidant effect. A structure-activity relationship data thus indicated that a 4'-monohydroxyl group, which can be oxidized to semiquinone radical but not up to quinone-like metabolite, is essential for prooxidant effect. When HL-60 cells were treated with not only a heme synthesis inhibitor succinyl acetone (SA) but also myeloperoxidase (MPO) inhibitors, the ROS level enhanced by apigenin was significantly reduced. The gathered data suggested that peroxidase-catalyzed production of apigenin B-ring phenoxyl radicals might be responsible for the prooxidant effect. This is supported by the observation that MPO is able to catalyze production of apigenin phenoxyl radicals, detected by an electron spin resonance-spin trapping technique. We also reveal that both SA and alpha-tocopherol enhance cellular susceptibility to apoptosis-inducing stimuli by apigenin. In conclusion, the prooxidant effect of apigenin is likely to oxidize a variety of thiols through the formation of phenoxyl radicals and thus seems to play a significant role in the abortive apoptotic pathway switching to necrotic cell death. PMID- 17870051 TI - Association between season and temperature and unstimulated parotid and submandibular/sublingual secretion rates. AB - OBJECTIVE: The purpose of the present study was to evaluate parotid and submandibular/sublingual (SM/SL) unstimulated salivary secretion rate in a group of healthy individuals in winter and summer, and to observe the effect of room adjusted temperature (air-conditioning) on salivary flow-rate in those seasons. DESIGN: Unstimulated salivary secretion rates of the right parotid and the SM/SL glands were measured in 50 healthy Israeli volunteers. Each volunteer was evaluated four times during the study: twice in winter (February-March) and twice in summer (July-August). RESULTS: Parotid and SM/SL salivary mean secretion rate in winter was significantly higher than in summer (p<0.02 and p<0.05, respectively). Room heating in winter lowered significantly the mean parotid flow. Air-conditioning cancelled almost completely the seasonal effects on parotid and SM/SL secretions. CONCLUSIONS: The results of this study suggest that room temperature is an important factor in measurement of salivary secretion rate. Hence, temperature should ideally be recorded and reported when assessing salivary flow-rates. PMID- 17870052 TI - Localisation of a candidate anion transporter to the surface of the malaria parasite. AB - PfSulP, encoded by the human malaria parasite Plasmodium falciparum, is a member of the sulphate permease family of anion transporter proteins. By transfecting the parasite with an epitope-tagged version of PfSulP, and detecting via western blot and indirect immunofluorescent assay microscopy, we show that PfSulP is localised to the surface of the intraerythrocytic parasite, where it is postulated to play a role in the flux of anions across the parasite plasma membrane. PMID- 17870053 TI - Effect of ScrF I polymorphism in the 2nd intron of the HMGCR gene on lipid lowering response to simvastatin in Chinese diabetic patients. AB - OBJECTIVE: To investigate whether ScrF I polymorphism in the 2nd intron of the HMG-COA reductase gene (HMGCR) influences serum lipid levels and whether this polymorphism affects the efficiency of the cholesterol lowering HMG-CoA reductase inhibitor, simvastatin. METHODS: One hundred sixty-eight patients with type 2 diabetes mellitus (T2DM) prospectively received simvastatin as a single-agent therapy (20mg day-1 p.o.) for 12 weeks. Serum lipid levels were determined before and after simvastatin treatment. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Subjects with the AA homozygotes had significantly higher serum very low-density lipoprotein cholesterol (VLDL-C) levels than those with the aa homozygotes. In addition, in 168 patients with T2DM who took 20mg simvastatin, the VLDL-C lowering effect by simvastatin in subjects with the aa homozygotes was significantly lower than in those with the Aa heterozygotes and AA homozygotes. CONCLUSIONS: Simvastatin treatment significantly decreased plasma lipids in all patients (P<0.01). Importantly, we demonstrate that ScrF I polymorphism of the HMGCR gene in patients with T2DM groups is associated with significant elevation of serum VLDL-C levels. Subjects with the AA homozygotes had significantly higher serum high VLDL-C levels than those with the Aa heterozygotes and aa homozygotes (AA: 2.18+/-0.51; Aa: 2.04+/-0.59, aa: 1.86+/-0.43, P<0.05 for comparison among three genotypes and P<0.01 for difference between AA and aa). Furthermore, this polymorphism tends to show an enhanced response to an HMG-CoA reductase inhibitor in terms of the cholesterol-lowering effect. In 168 patients with T2DM who took 20mg simvastatin, the VLDL-C lowering effect by simvastatin in subjects with the AA homozygotes was significantly lower than in those with the Aa heterozygotes and aa homozygotes (the reduction in serum VLDL-C levels; 37.03+/-5.67 versus 28.97+/-4.96, P<0.01; 34.62+/-5.87 versus 28.97+/-4.96, P<0.05). These results suggest that the HMGCR gene may serve as a modifier gene for hypercholesterolemia in Chinese diabetic patients. PMID- 17870054 TI - Ubiquitin is degraded by the ubiquitin system as a monomer and as part of its conjugated target. AB - An important problem concerning regulation of the ubiquitin-proteasome system (UPS) relates to the stability of its own components and the mechanisms of their degradation. It has been demonstrated that monomeric ubiquitin is relatively stable and is probably degraded by the proteasome. It has also been shown that it is destabilized following inactivation of deubiquitinating enzymes, suggesting that failure to release it, results in its concomitant degradation along with its target. Here, we demonstrate that conjugation of monomeric ubiquitin requires both its internal lysines and N-terminal residue. Interestingly however, the degradation of the monomeric species requires also a short C-terminal extension, implying that unlike conjugation, entry into the proteasomal chamber requires a tail that can be generated in the cell via several distinct mechanisms. We further show that accelerated intracellular degradation induced by stress results in depletion of ubiquitin, supporting the notion that ubiquitin is also degraded as part of the chain conjugated to its target substrate. PMID- 17870055 TI - Azasterols impair Giardia lamblia proliferation and induces encystation. AB - The effects of sterol biosynthesis inhibitors on growth and fine structure of Giardia lamblia P1 strain cultures were analyzed. Azasterols demonstrated high efficacy in killing cells. The IC(50) values for 22,26-azasterol and 24(R,S),25 epiminolanosterol were 7muM and 170nM, respectively. Morphological analysis showed that azasterols induced changes in G. lamblia ultrastructure. The most significant alterations were: (a) considerable increase of the size of the peripheral vesicles, which are part of the parasite endosomal-lysosomal system; (b) appearance of autophagosomal structures; and (c) induction of differentiation, followed by an abnormal enlargement of encystation secretory vesicles. We propose that azasterols are effective chemotherapeutic drugs against Giardia lamblia in vitro and may have another target in cells besides sterol biosynthesis. PMID- 17870056 TI - Methylation status of the reelin promoter region in the brain of schizophrenic patients. AB - BACKGROUND: Hypermethylation of the reelin (RELN) promoter region and the reduced levels of its messenger RNA and protein have been implicated in the pathophysiology of schizophrenia. We intended a technical replication of recent studies that observed hypermethylation of CpG or CpNpG sites in the RELN promoter region in the brain of schizophrenic patients. METHODS: The DNA methylation status of the promoter region of RELN was examined by using the pyrosequencing method in the prefrontal cortices of 14 patients with schizophrenia and 13 control subjects. RESULTS: All of the CpG and two proposed CpNpG sites analyzed showed no detectable DNA methylation (< 5%) in both control subjects and patients with schizophrenia. No detectable DNA methylation was observed in both gray and white matter, excluding the possibility of cellular heterogeneity of start materials. CONCLUSIONS: We did not confirm the hypermethylation of the RELN promoter region in the brains of schizophrenic patients, suggested in the previous studies. PMID- 17870057 TI - IGF2 knockout mice are resistant to kainic acid-induced seizures and neurodegeneration. AB - Insulin-like growth factor 2 (Igf2), a member of the insulin gene family, is important for brain development and has known neurotrophic properties. Though Igf2, its receptors, and binding proteins, are expressed in the adult CNS, their role in the adult brain is less well-understood. Here we studied how Igf2 deficiency affects brains of adult Igf2 knockout (Igf2(-/-)) mice following neurotoxic insult produced by the glutamate analog kainic acid (KA). Igf2(-/-) mice exhibited attenuated epileptiform activity in response to KA and were less susceptible to hippocampal neurodegeneration compared with Igf2(+/+) mice. Other brain areas protected by the lack of Igf2 included the amygdala complex, septal nuclei, and thalamic region. Apoptosis, as determined by TUNEL and Hoechst 33342 staining, was accordingly less for Igf2(-/-) mice. Hippocampal slices from Igf2( /-) mice also were protected against the effects epileptogenic effects of KA compared to Igf2(+/+) mice suggesting that neuroprotection afforded by a lack of Igf2 may be developmental in origin and experiments demonstrating enhanced synaptic inhibition in slices taken from Igf2(-/-) mice support this hypothesis. Taken together, these results suggest that Igf2 may be important for mechanisms and circuits that contribute to neurodegeneration and epilepsy. PMID- 17870058 TI - Peptide YY(3-36)-induced inhibition of food intake in female monkeys. AB - Peptide YY (PYY) is produced in L cells of the intestine and is released after eating. PYY circulates in a truncated form designated PYY(3-36). PYY(3-36) is thought to be a physiologic anorexigenic peptide. The objective of the current study was to test the effect of exogenous PYY(3-36) on food intake in non-human primates exposed to different ovarian steroid milieus. The study was conducted in four ovariectomized cynomolgus monkeys replaced with estrogen alone for 2 weeks followed by estrogen in combination with progesterone for 2 weeks to mimic the menstrual cycle. The effect of PYY(3-36) on food intake was tested during each week of the simulated menstrual cycle by comparing the 2 h food intake following intracerebroventricular (icv) injection of artificial cerebrospinal fluid (aCSF) or PYY(3-36). Despite considerable variation in food intake following aCSF, PYY(3 36) consistently inhibited food consumption, except during week 2 of estrogen plus progesterone replacement. PYY(3-36) reduced food consumption by 16.2 g (95% confidence interval (CI)=4.5-27.9 g) and 26.6 g (95% CI=7.3-45.9 g) in weeks 1 and 2 respectively of estrogen only treatment and by 38.2 g (95% CI=26.1-50.2 g) in week 1 of estrogen plus progesterone treatment. In contrast, PYY(3-36) injected in week 2 of estrogen plus progesterone did not consistently inhibit food intake (13.1 g; CI=-49.5-75.7). This is the first study to report the effect of PYY(3-36) on food consumption in female monkeys. We conclude that icv administration of PYY(3-36) has a strong anorexic effect in female cynomolgus monkeys and that sensitivity to PYY(3-36) may be influenced by the ovarian steroid milieu. PMID- 17870059 TI - Quantitative immuno-electron microscopic analysis of depolarization-induced expression of PGC-1alpha in cultured rat visual cortical neurons. AB - Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC- 1alpha) is a coactivator of nuclear receptors and other transcription factors that regulate several metabolic processes, including mitochondrial biogenesis, energy homeostasis, respiration, and gluconeogenesis. PGC-1alpha plays a vital role in stimulating genes that are important to oxidative metabolism and other mitochondrial functions in brown adipose tissue and skeleton muscles, but the significance of PGC-1alpha in the brain remains elusive. The goal of our present study was to determine by means of quantitative immuno-electron microscopy the expression of PGC-1alpha in cultured rat visual cortical neurons under normal conditions as well as after depolarizing stimulation for varying periods of time. Our results showed that: (a) PGC-1alpha was normally located in both the nucleus and the cytoplasm. In the nucleus, PGC-1alpha was associated mainly with euchromatin rather than heterochromatin, consistent with active involvement in transcription. In the cytoplasm, it was associated mainly with free ribosomes. (b) Neuronal depolarization by KCl for 0.5 h induced a significant increase in PGC-1alpha labeling density in both the nucleus and the cytoplasm (P<0.01). The heightened expression continued after 1 and 3 h of depolarizing treatment (P<0.01), but decreased from 5 h onward and returned to baseline level by 10 h. These results indicate that PGC-1alpha responds very early to increased neuronal activity by synthesizing more proteins in the cytoplasm and translocating them to the nucleus for gene activation. PGC-1alpha level in neurons is, therefore, tightly regulated by neuronal activity. PMID- 17870060 TI - Attentional control of associative learning--a possible role of the central cholinergic system. AB - How does attention interact with learning? Kruschke [Kruschke, J.K. (2001). Toward a unified Model of Attention in Associative Learning. J. Math. Psychol. 45, 812-863.] proposed a model (EXIT) that captures Mackintosh's [Mackintosh, N.J. (1975). A theory of attention: Variations in the associability of stimuli with reinforcement. Psychological Review, 82(4), 276-298.] framework for attentional modulation of associative learning. We developed a computational model that showed analogous interactions between selective attention and associative learning, but is significantly simplified and, in contrast to EXIT, is motivated by neurophysiological findings. Competition among input representations in the internal representation layer, which increases the contrast between stimuli, is critical for simulating these interactions in human behavior. Furthermore, this competition is modulated in a way that might be consistent with the phasic activation of the central cholinergic system, which modulates activity in sensory cortices. Specifically, phasic increases in acetylcholine can cause increased excitability of both pyramidal excitatory neurons in cortical layers II/III and cortical GABAergic inhibitory interneurons targeting the same pyramidal neurons. These effects result in increased attentional contrast in our model. This model thus represents an initial attempt to link human attentional learning data with underlying neural substrates. PMID- 17870061 TI - Hypobaric hypoxia damages the hippocampal pyramidal neurons in the rat brain. AB - Hypobaric hypoxia (HH), a predisposing environmental condition at high altitude (HA), encountered by many mountaineers, jeopardizes their normal physiology like motor coordination and cognitive functions. A large body of evidence shows that HH has deleterious effect on cognitive functions. Among them the hippocampal dependent memory deficit is well known. However, our current understanding of the mechanistic details of cognitive deficits at HA remains largely unclear and hence limits a solution for this problem. Therefore, the present study was designed to investigate the temporal component of the hippocampal pyramidal neuron damage in the rat brain subjected to chronic HH exposure. Three groups (sham HH, 3 days HH and 7 days HH) of rats were exposed to simulated HH equivalent to 6100 m in an animal decompression chamber for 3 or 7 days. Later, the hippocampal (CA1 and CA3) neurons were analysed for the cell morphology, neurodegeneration and DNA fragmentation. The CA1 and CA3 neurons showed HH induced neuronal pyknosis, cell shrinkage, and consequent inter-cellular vacuolization in the CA1 and CA3 areas. In addition, the total neuron (intact) numbers and mean surface area were decreased. The number of dead neurons increased significantly following exposure to HH for 3 or 7 days. The neurodegenerative (Fluoro jade B) and apoptotic (TUNEL) markers were more positive in CA1 and CA3 neurons. The magnitude of morphological changes, neurodegeneration and apoptosis was enhanced in 7 days HH group than 3 days HH group. Our studies indicate that CA3 neurons are more vulnerable to HH than CA1 neurons, and that may destabilize the neural circuits in the hippocampus and thus cause memory dysfunction. PMID- 17870062 TI - Effects of sexual experience on conspecific odor preference and male odor-induced activation of the vomeronasal projection pathway and the nucleus accumbens in female rats. AB - In the present study in estrogen-progesterone primed ovariectomized female rats, we examined the expression of a preference for male odors and male odor-induced Fos immunoreactivity throughout the vomeronasal projection pathway and the nucleus accumbens (NAcc), using both sexually experienced and sexually naive subjects. Female rats significantly preferred airborne odors and soiled bedding from sexually active males over those from estrous females, irrespective of the presence or absence of prior sexual experience. On the other hand, the brain regions in which exposure to male-soiled bedding significantly increased Fos expression were different between sexually experienced and sexually naive subjects. Significant increment of Fos expression in the posterior-dorsal medial amygdala (MePD) and the bed nucleus of stria terminalis (BNST) in forebrain, as well as the accessory olfactory bulb, was observed in both groups of subjects. Fos expression in the anterior-dorsal medial amygdala (MeAD), the medial preoptic area (mPOA) and the NAcc core, however, was significantly increased only in the sexually experienced subjects. These results suggested that male odor-induced activations of the MePD and/or the BNST, but not of the MeAD, the mPOA and the NAcc core, are required for the expression of a male-directed odor preference in female rats. PMID- 17870063 TI - Response of lead-induced oxidative stress and alterations in biogenic amines in different rat brain regions to combined administration of DMSA and MiADMSA. AB - The present study was planned to investigate if combined administration of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) could achieve better recovery in the altered biochemical parameters suggestive of brain oxidative stress and depletion of lead from blood and brain following acute lead exposure. Male Wistar rats were exposed to lead nitrate (50 mg/kg, i.p., once daily for 5 days) followed by treatment with the above chelating agents using two different doses of 25 or 50 mg/kg (orally) either alone and in combination once daily for five consecutive days. Lead exposure resulted in the significant inhibition of delta-aminolevulinic acid dehydratase activity and depletion of glutathione (GSH) in blood. These changes were accompanied by significant reduction in blood hemoglobin, RBC levels and superoxide dismutase and catalase activities. Significant increase in blood reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) levels were noted. We observed marked increase in brain ROS level while GSH/oxidized glutathione ratio showed significant decrease accompanied by a significant increase in blood and brain lead concentration. The levels of norepinephrine, dopamine and serotonin in different brain regions were also altered on lead exposure. Co-administration of DMSA and MiADMSA particularly at the lower dose was most effective in the recovery of lead-induced changes in the hematological variables and oxidative stress and resulted in more pronounced depletion of lead from blood and brain compared to monotherapy with these chelators. On the other hand, combined administration of MiADMSA (50 mg/kg) in combination with DMSA (25 mg/kg each) had additional beneficial effect over the individual effect of chelating agent in the recovery of altered levels of brain biogenic amines. The study suggests that administration of MiADMSA is generally a better lead chelator than DMSA while combined administration of DMSA and MiADMSA might be a better treatment option compared to monotherapy at least in the removal of lead from the target tissues. PMID- 17870064 TI - Sex-contingent face aftereffects depend on perceptual category rather than structural encoding. AB - Many studies have used visual adaptation to investigate how recent experience with faces influences perception. While faces similar to those seen during adaptation phases are typically perceived as more 'normal' after adaptation, it is possible to induce aftereffects in one direction for one category (e.g. female) and simultaneously induce aftereffects in the opposite direction for another category (e.g. male). Such aftereffects could reflect 'category contingent' adaptation of neurons selective for perceptual category (e.g. male or female) or 'structure-contingent' adaptation of lower-level neurons coding the physical characteristics of different face patterns. We compared these explanations by testing for simultaneous opposite after effects following adaptation to (a) two groups of faces from distinct sex categories (male and female) or (b) two groups of faces from the same sex category (female and hyper female) where the structural differences between the female and hyper-female groups were mathematically identical to those between male and female groups. We were able to induce opposite aftereffects following adaptation between sex categories but not after adaptation within a sex category. These findings indicate the involvement of neurons coding perceptual category in sex-contingent face aftereffects and cannot be explained by neurons coding only the physical aspects of face patterns. PMID- 17870065 TI - Abnormalities in cell proliferation and apico-basal cell polarity are separable in Drosophila lgl mutant clones in the developing eye. AB - In homozygous mutants of Drosophila lethal-2-giant larvae (lgl), tissues lose apico-basal cell polarity and exhibit ectopic proliferation. Here, we use clonal analysis in the developing eye to investigate the effect of lgl null mutations in the context of surrounding wild-type tissue. lgl- clones in the larval eye disc exhibit ectopic expression of the G1-S regulator, Cyclin E, and ectopic proliferation, but do not lose apico-basal cell polarity. Decreasing the perdurance of Lgl protein in larval eye disc clones, by forcing extra proliferation of lgl- tissue (using a Minute background), leads to a loss in cell polarity and to more extreme ectopic cell proliferation. Later in development at the pupal stage, lgl mutant photoreceptor cells show aberrant apico-basal cell polarity, but this is not associated with ectopic proliferation, presumably because cells are differentiated. Thus in a clonal context, the ectopic proliferation and cell polarity defects of lgl- mutants are separable. Furthermore, lgl- mosaic eye discs have alterations in the normal patterns of apoptosis: in larval discs some lgl- and wild-type cells at the clonal boundary undergo apoptosis and are excluded from the epithelia, but apoptosis is decreased elsewhere in the disc, and in pupal retinas lgl- tissue shows less apoptosis. PMID- 17870066 TI - Accelerated telomere shortening and replicative senescence in human fibroblasts overexpressing mutant and wild-type lamin A. AB - LMNA mutations are responsible for a variety of genetic disorders, including muscular dystrophy, lipodystrophy, and certain progeroid syndromes, notably Hutchinson-Gilford Progeria. Although a number of clinical features of these disorders are suggestive of accelerated aging, it is not known whether cells derived from these patients exhibit cellular phenotypes associated with accelerated aging. We examined a series of isogenic skin fibroblast lines transfected with LMNA constructs bearing known pathogenic point mutations or deletion mutations found in progeroid syndromes. Fibroblasts overexpressing mutant lamin A exhibited accelerated rates of loss of telomeres and shortened replicative lifespans, in addition to abnormal nuclear morphology. To our surprise, these abnormalities were also observed in lines overexpressing wild type lamin A. Copy number variants are common in human populations; those involving LMNA, whether arising meiotically or mitotically, might lead to progeroid phenotypes. In an initial pilot study of 23 progeroid cases without detectable WRN or LMNA mutations, however, no cases of altered LMNA copy number were detected. Nevertheless, our findings raise a hypothesis that changes in lamina organization may cause accelerated telomere attrition, with different kinetics for overexpession of wild-type and mutant lamin A, which leads to rapid replicative senescence and progroid phenotypes. PMID- 17870067 TI - Syndecans promote integrin-mediated adhesion of mesenchymal cells in two distinct pathways. AB - Syndecans are transmembrane proteoglycans that support integrin-mediated adhesion. Well documented is the contribution of syndecan-4 that interacts through its heparan sulphate chains to promote focal adhesion formation in response to fibronectin domains. This process has requirements for integrin and signaling through the cytoplasmic domain of syndecan-4. Here an alternate pathway mediated by the extracellular domains of syndecans-2 and -4 is characterized that is independent of both heparan sulphate and syndecan signaling. This pathway is restricted to mesenchymal cells and was not seen in any epithelial cell line tested, apart from vascular endothelia. The syndecan ectodomains coated as substrates promoted integrin-dependent attachment, spreading and focal adhesion formation. Syndecan-4 null cells were competent, as were fibroblasts compromised in heparan sulphate synthesis that were unable to form focal adhesions in response to fibronectin. Consistent with actin cytoskeleton organization, the process required Rho-GTP and Rho kinase. While syndecan-2 and -4 ectodomains could both promote integrin-mediated adhesion, their pathways were distinct, as shown by competition assays. Evidence for an indirect interaction of beta1 integrin with both syndecan ectodomains was obtained, all of which suggests a distinct mechanism of integrin-mediated adhesion. PMID- 17870069 TI - Geldanamycin, a HSP90 inhibitor, attenuates the hypoxia-induced vascular endothelial growth factor expression in retinal pigment epithelium cells in vitro. AB - Hypoxia is the most common factor contributing to the pathogenesis of choroidal neovascularization, which is the major cause for blindness and occurs in proliferative diabetic retinopathy and age-related macular degeneration. The purpose of this study is to investigate the role of retinal pigment epithelial (RPE) cells in the regulation of subretinal neovascularization under hypoxia and the possible function of a heat shock protein 90 (HSP90) inhibitor, geldanamycin (GA), in the regulation of VEGF expression. An in vitro hypoxic experimental model was used to mimic the ischemic microenvironment of RPE cells. The cell growth was measured by proliferation assay and the morphological observation was documented by microscope. The gene expression of VEGF, hsp70, hsp90alpha and hsp90beta were measured using semi-quantitative RT-PCR. The VEGF release from RPE cells were detected by ELISA. No alteration in growth rate and cell morphology under 1% O(2) condition for 24h was noticed. The proangiogenic growth factor VEGF, but not bFGF, released from hypoxia-treated cells were significantly higher than those of normoxic controls. A similar tendency of VEGF(165) isoform gene expression, detected by RT-PCR, was noticed in hypoxia-treated cells. Heat shock pretreatment elevated hsp70 and VEGF(165) gene expression and augmented the hypoxia-induced VEGF gene expression and protein release. Pretreatment with GA can significantly suppress the hypoxia-induced VEGF gene expression in and peptide release from RPE cells. These in vitro findings suggest that HSP90 inhibitors could be considered as novel anti-angiogenesis agents for diseases with intraocular neovascularization. PMID- 17870070 TI - Babesia gibsoni: identification of an immunodominant, interspersed repeat antigen. AB - In this report, an immunodominant antigen called BgIRA from Babesia gibsoni is identified and described. A highly repetitive antigen was screened from a cDNA library. The genomic BgIRA gene exists as single cope gene and contains 10 introns. BgIRA plays a dominant role in the immune response in dogs infected with B. gibsoni. The specificity and sensitivity of the rBgIRA in an ELISA indicated that this antigen might be useful in a diagnostic test. PMID- 17870068 TI - Uveal melanoma expression of indoleamine 2,3-deoxygenase: establishment of an immune privileged environment by tryptophan depletion. AB - The enzyme indoleamine 2,3-dioxygenase (IDO) catalyzes degradation of tryptophan, an essential amino acid required for lymphocyte activation and proliferation. Many tumors express IDO which implies that it acts as a mechanism to evade T cell mediated immune attack, and also to establish an immunosuppressive tumor microenvironment. The purpose of this study was to determine whether primary and metastatic uveal melanoma expressed the IDO gene and whether uveal melanoma cells could deplete tryptophan. In situ expression of IDO in primary uveal melanoma from tumor bearing eyes and metastatic uveal melanoma liver tissues was determined by immunohistostaining with IDO-specific antibody. Reverse transcription PCR was used to assess IDO gene transcription by primary and metastatic uveal melanoma cell lines. IDO protein expression was determined by Western blot of uveal melanoma cell protein lysate. IDO catalytic activity was assessed by measuring the presence of kynurenine, a product generated by tryptophan degradation, in uveal melanoma culture supernatants. Primary uveal melanoma from tumor-bearing eyes and metastatic uveal melanoma from the liver did not express IDO in situ. IDO was not constitutively expressed in either primary or metastatic uveal melanoma cell lines. However, stimulation of primary and metastatic uveal melanoma cell cultures with interferon-gamma (IFN-gamma) universally upregulated both IDO gene and protein expression. Culture supernatants from IFN-gamma treated primary and metastatic uveal melanoma cell cultures contained elevated levels of kynurenine. Addition of the IDO inhibitor 1 methyl dl-tryptophan significantly diminished kynurenine levels in IFN-gamma treated uveal melanoma cell cultures. The results from this study suggest that IFN-gamma inducible IDO upregulation by primary and metastatic uveal melanoma may generate a local immune privileged microenvironment to promote escape from T cell mediated immune surveillance. PMID- 17870071 TI - Entamoeba histolytica: fibrilar aggregates in dividing trophozoites. AB - Entamoeba histolytica trophozoite cytokinesis is dependent upon cytoskeletal elements such as filamentous actin and myosin. Here we present confocal and transmission electron microscopy studies of this process. A sequence in the formation of the contractile ring was shown with rhodamine-phalloidine staining. Ultrastructural analysis revealed the presence of fibrilar aggregates in the cytoplasm of dividing trophozoites. Among them two filaments of different diameter were identified. These aggregates presented repeating assemblies of thin and thick filaments that in cross section revealed a muscle-like appearance. Our results suggest that these aggregates constitute the contractile ring responsible for the separation of daughter cells. PMID- 17870073 TI - The hepatic PP1 glycogen-targeting subunit interaction with phosphorylase a can be blocked by C-terminal tyrosine deletion or an indole drug. AB - The inhibition of hepatic glycogen-associated protein phosphatase-1 (PP1-G(L)) by glycogen phosphorylase a prevents the dephosphorylation and activation of glycogen synthase, suppressing glycogen synthesis when glycogenolysis is activated. Here, we show that a peptide ((280)LGPYY(284)) comprising the last five amino acids of G(L) retains high-affinity interaction with phosphorylase a and that the two tyrosines play crucial roles. Tyr284 deletion abolishes binding of phosphorylase a to G(L) and replacement by phenylalanine is insufficient to restore high-affinity binding. We show that a phosphorylase inhibitor blocks the interaction of phosphorylase a with the G(L) C-terminus, suggesting that the latter interaction could be targeted to develop an anti-diabetic drug. PMID- 17870072 TI - Protocols for gene silencing in schistosomes. AB - Schistosomes are parasitic platyhelminths that infect over 200 million people globally. In recent years there have been many advances in schistosome genomics and proteomics and in the development of molecular tools for use with these parasites. Among the more promising methodologies is RNA interference (RNAi) which is a mechanism by which gene-specific double-stranded RNA (dsRNA) triggers degradation of homologous mRNA transcripts. We aim to develop effective protocols utilizing RNAi for use in the intra-mammalian life stages of Schistosoma mansoni. In this work, the gene encoding alkaline phosphatase (SmAP) was targeted by exposing the parasites to dsRNA encoding part of the SmAP coding region. SmAP is known to be expressed in a variety of parasite tissues. We report that both long dsRNAs as well as synthetic short inhibitory RNAs (siRNAs) are effective at eliciting SmAP gene suppression in cultured schistosomula and in adult males and females. Electroporation as a mode of dsRNA delivery is more efficient than simply soaking the parasites in an equivalent dose. Relative SmAP RNA levels >90% lower than controls were routinely detected, when measured 2 days after treatment by electroporation, using quantitative real-time PCR. Commensurate with this decline in SmAP RNA, relative alkaline phosphatase enzyme activity levels >70% lower than controls were detected, 5 days after treatment. Protocols described here that result in the robust suppression of target genes in intravascular schistosomes may have wide applicability and promote functional schistosome genomics. PMID- 17870074 TI - Women's pupillary responses to sexually significant others during the hormonal cycle. AB - Women's sexual preferences can change over the hormonal cycle, as several studies, based on responses to questionnaires, diaries, and ratings of photographs, have indicated increased sexual interests around the time of ovulation. However, fewer studies have measured changes in attention or interest to sexually significant stimuli in terms of physiological responses that are not under voluntary control and measure sexual interest indirectly (i.e., without mention of sexual feelings or activities). In the present study, we indexed changes in sexual interest in terms of changes in the eye pupil's size. Pupillary diameter is known to have a proportional relation to the observer's level of interest and attention to a visual stimulus as well as to physical pleasure. Fourteen women (7 being "pill" users) viewed photos on a computer screen while their pupil diameters were recorded using an infrared eye-tracking device. Three measures were taken for each participant during three time windows that estimated the ovulatory, luteal, and menstrual phase of the cycle. We found an increase in mean pupil diameter for sexually significant stimuli during the fertile phase and this pupillary change was also specific to pictures of the participants' actual sexual partners. Moreover, this effect was only seen for women who did not use oral contraceptives. These findings confirm that women's attention for sexually significant stimuli is higher during their fertile phase of the menstrual cycle, and that changes in sexual interest are implicitly measurable using pupillometry. PMID- 17870075 TI - A tuning algorithm for model predictive controllers based on genetic algorithms and fuzzy decision making. AB - Model Predictive Control is a valuable tool for the process control engineer in a wide variety of applications. Because of this the structure of an MPC can vary dramatically from application to application. There have been a number of works dedicated to MPC tuning for specific cases. Since MPCs can differ significantly, this means that these tuning methods become inapplicable and a trial and error tuning approach must be used. This can be quite time consuming and can result in non-optimum tuning. In an attempt to resolve this, a generalized automated tuning algorithm for MPCs was developed. This approach is numerically based and combines a genetic algorithm with multi-objective fuzzy decision-making. The key advantages to this approach are that genetic algorithms are not problem specific and only need to be adapted to account for the number and ranges of tuning parameters for a given MPC. As well, multi-objective fuzzy decision-making can handle qualitative statements of what optimum control is, in addition to being able to use multiple inputs to determine tuning parameters that best match the desired results. This is particularly useful for multi-input, multi-output (MIMO) cases where the definition of "optimum" control is subject to the opinion of the control engineer tuning the system. A case study will be presented in order to illustrate the use of the tuning algorithm. This will include how different definitions of "optimum" control can arise, and how they are accounted for in the multi-objective decision making algorithm. The resulting tuning parameters from each of the definition sets will be compared, and in doing so show that the tuning parameters vary in order to meet each definition of optimum control, thus showing the generalized automated tuning algorithm approach for tuning MPCs is feasible. PMID- 17870076 TI - Simple fistulas: diagnosis and management in low-resource settings--a descriptive report. AB - Obstetric fistulas occur in developing countries because of the scarcity or complete absence of obstetric services. The magnitude of the problem is unknown but thought to be sizeable. This article describes a basic approach to the care of women with fistulas in a low-resource rural hospital in northern Ghana, where the results were similar to those obtained at better-equipped centers. The facility includes an outpatient clinic for history taking and clinical examinations, and a laboratory for hemoglobin concentration assessment, sickling test, blood grouping, and cross-matching when necessary. Anesthesia consists of a spinal anesthesia given by the surgeon and monitored by a nurse while the surgeon scrubs up before repairing the fistula. Surgery is performed with the patient in exaggerated lithotomy position, and a bed sheet used as a sling prevents her from falling backwards. The patients are kept at the hospital for 14 days postoperatively for continuous bladder drainage. PMID- 17870077 TI - Incontinence in Malawi: analysis of a proxy measure of vaginal fistula in a national survey. AB - OBJECTIVE: To document the first effort to collect national lifetime prevalence data on vaginal fistulas and discern the usefulness of the measure. METHODS: The 11,698 women successfully interviewed in the 2005 Malawi Demographic and Health Survey were asked whether they had ever experienced leakage of urine or stool from their vagina. Multivariate techniques were then used to determine factors associated with fistula symptoms. RESULTS: The relationships between fistula symptoms and wealth and fistula symptoms and education were negative and monotonic. Rural women were 40% more likely than urban women to report fistula symptoms. Women who had experienced a stillbirth were 66% more likely to report the symptoms, and those who had experienced sexual violence were 71% more likely to report the symptoms. A crude fistula rate of 15.6 per 1000 live births was found for Malawi. CONCLUSIONS: Survey methods may be used to capture the prevalence of vaginal fistula cases in a given country, but further work is needed to improve the sensitivity and specificity of the questions asked. PMID- 17870078 TI - A community program for women's health and development: implications for the long term care of women with fistulas. AB - The Women's Health and Development project, also known as FORWARD, was set up to improve the social, economic, and health status of women affected with vesico vaginal fistulas. The project takes a holistic approach not only by providing surgical repair and rehabilitation, but also through the development of skills that will help women improve their physical and economic well-being. In addition, to prevent vesico-vaginal fistulas in young women, the project organizes campaigns to bring about a culture fostering the education and empowerment of women. These campaigns also raise awareness on general health, reproductive health and rights, and the necessity of integrating women into mainstream community development programs. In 2006, the project was in its seventh year and still recording success. PMID- 17870079 TI - Fistula Fortnight: innovative partnership brings mass treatment and public awareness towards ending obstetric fistula. AB - OBJECTIVE: As part of the global Campaign to End Fistula, the Fistula Fortnight, a 2-week mass obstetric fistula treatment project, was organized in northern Nigeria to contribute to reducing the backlog of untreated fistulas and raise awareness regarding obstetric fistulas and safe motherhood. METHODS: An array of partners joined forces to provide free surgical treatment, strengthen the capacity of existing facilities to manage obstetric fistulas, and utilize media strategies to raise awareness. RESULTS: The Fistula Fortnight took place from February 21 to March 6, 2005, at 4 established fistula repair centers in the northern Nigeria states of Kano, Katsina, Kebbi, and Sokoto. A total of 569 women received treatment, with an 87.8% rate of successful closures. The highly publicized event also raised awareness on the issue of obstetric fistula and helped put a face to maternal deaths. CONCLUSION: The Fortnight, which required extensive and thoughtful planning involving many persons cognizant of health system and quality of care issues, was effective in drawing attention to the vast fistula problem and contributed to reducing the backlog of patients. PMID- 17870080 TI - Micro-ultrasound imaging assessment of carotid plaque characteristics in apolipoprotein-E knockout mice. AB - This study was aimed to test the hypothesis that noninvasive assessment of carotid plaques can be achieved by high-resolution micro-ultrasound imaging in apolipoprotein-E knockout (apoE-KO) mice. Forty-two male apoE-KO mice were fed a high-fat diet and atherosclerotic lesions in the left common carotid artery were induced by perivascular placement of constrictive collars. Eight weeks after surgery, all mice were divided into interventional group (n=21) which received mental stress stimulation and intraperitoneal injection of lipopolysaccharide, and control group (n=21) which received only 0.9% sodium chloride solution for 4 weeks. Plaque morphology and flow velocities were evaluated by micro ultrasonography. The results showed that micro-ultrasound imaging and corresponding cross-sectional histopathology data revealed positive correlations for plaque area, intima-medial thickness (IMT), eccentric index (EI) and remodeling index (RI) (all p<0.05). Ultrasound-derived IMT, EI and RI in the ruptured plaques were significantly greater than those in the nonruptured plaques (all p<0.05). Maximal flow velocity (Vmax) was higher in the ruptured plaque sites compared with nonruptured plaques sites (p<0.001). Multivariate logistic regression analysis revealed that IMT and Vmax were independent predictors of plaque rupture. In conclusion, micro-ultrasound imaging provides a reliable approach to the noninvasive and quantitative assessment of carotid plaques in apoE-KO mice. PMID- 17870081 TI - Parameters affecting microwave-assisted extraction of organophosphorus pesticides from agricultural soil. AB - This work describes an optimised method for the determination of six representative organophosphorus pesticides (OPPs) (diazinon, parathion, methyl pirimiphos, methyl parathion, ethoprophos, and fenitrothion) in agricultural soils. The method is based on microwave-assisted extraction using a water methanol modified mixture for desorption and simultaneous partitioning on n hexane (MAEP), together with gas chromatography-flame photometric detection (GC FPD). To improve GC-FPD signals (peak intensity and shape) olive oil was used effectively as a "matrix mimic". The optimisation of the extraction method was achieved in two steps: an initial approach through experimental design and principal component analysis where recovery of compounds using a water-methanol mixture ranged from 54 to 77%, and the second one by studying the addition of KH2PO4 to the extracting solution where recoveries were significantly increased, molecular replacing of OPPs from adsorption sites by phosphate being the probable extraction mechanism. Under optimised conditions, recoveries of pesticides from different soils were higher than 73%, except for methyl parathion in some soils, with SD equal or lower than 11% and detection limits ranging from 0.004 to 0.012 microg g(-1). The proposed method was used to determine OPPs in soil samples from different agricultural zones of Chile. PMID- 17870082 TI - Non-discriminating flash pyrolysis and thermochemolysis of heavily contaminated sediments from the Hamilton Harbor (Canada). AB - Analytical pyrolysis of sediments contaminated with pollutants of medium to high molecular weights (up to approximately 500 Da) is very challenging when using conventional pyrolysis systems due to discrimination of high molecular weight analytes. In the framework of this contribution, non-discriminating pyrolysis and thermochemolysis using rapid heating in a Silcosteel capillary were applied to study organic pollutants in heavily contaminated sediments taken from the Hamilton Harbor. The novel pyrolysis approach, requiring very small amounts of sample, turned out to be very useful as a rapid screening method, e.g. for risk assessment studies, proving superior to commonly used solvent extraction. Main pollutants in the sediments under study included aromatic hydrocarbons, chiefly originating from coal tar and petroleum. Polycyclic aromatic hydrocarbons (PAHs) beyond six-rings, including coronene and truxene, could be detected. Sequential tetramethyl ammonium hydroxide-induced thermochemolysis performed at 500 and 750 degrees C enabled the differentiation between organic pollutants sorbed onto the sediment matrix on the one hand, and structural moieties of the condensed polymeric humic sediment matrix along with bound residues on the other hand. Thermochemolysis at 500 degrees C removed sorbates quantitatively, leaving only bare polymeric humic matrix. Significant PAH source indicators provided evidence that the lipidic fraction sorbed onto the sediments originated from PAHs formed chiefly in coal combustion processes. The polymeric humic organic matter network of the less polluted sediment was mainly of petrogenic origin, whereas black carbon, kerogen, etc. contributed to the organic carbon of the heavily polluted sediment. Thermochemolysis at 500 degrees C was also used to study fatty acid profiles of the sediments. The fatty acid methyl ester patterns obtained for the two sites under study differed significantly, with strong indications that microbial attenuation of the pollutants at the heavily polluted site 2 was strongly suppressed. PMID- 17870083 TI - Influence of the Stern layer on electrokinetic phenomena in porous media. AB - The Stern layer has been included in the description of electrolytes in a charged porous medium, with possibly large zeta potentials. The surface charge density, the conductivity, and the electroosmotic coupling coefficient are calculated for various porous structures and various physico-chemical conditions. The saturation of the Stern layer is analyzed, as well as its consequences for the macroscopic properties of the medium. The discontinuous character of the solid interface has an important influence on the macroscopic conductivity and the electroosmotic coefficient. PMID- 17870084 TI - Effect of UV and visible light on photocatalytic reduction of lead and cadmium over titania based binary oxide materials. AB - Uniform sized silica and zirconia mixed titania samples were prepared in presence of a surfactant (CETAB) using controlled hydrolysis of corresponding metal alkoxides. Photocatalytic activity towards reduction of lead and cadmium metal in aqueous solution was evaluated both in UV and visible light in a 100 ml capacity reactor. In particular mixing of 10 wt% silica with titania not only increases the surface area of the material but also increases the photocatalytic activity in UV light. Whereas mixing of zirconia with titania proved to be beneficial for visible light reaction. However, addition of hole scavenger increases the activity many folds and complete removal of Pb(2+) and Cd(2+) was possible in 60 min of reaction using synthesized catalysts. Among all the organic hole scavengers used, sodium formate is found to be the most active one. Interestingly quite high metal removal (89%) is also observed in presence of visible light within 60 min of reaction. Thus the above study indicates that the presence of certain oxides in low quantity (10 wt%) with titania can facilitates the photocatalytic process selectively in UV as well as visible light. PMID- 17870085 TI - Adsorption behavior, thermodynamics, and mechanism of phenol on polymeric adsorbents with amide group in cyclohexane. AB - Macroporous cross-linked poly(N-methyl-N-p-vinylbenzylacetamide) (PMVBA), poly(N methyl-N-p-vinylbenzylcaprolactam) (PMVBC), and poly(N-methyl-N-p vinylbenzylurea) (PMVBU) were synthesized and their adsorption behavior for phenol in cyclohexane was investigated. The results indicated that the adsorption capacities of phenol on the three adsorbents followed the order PMVBU > PMVBA > PMVBC. Adsorption isotherms of phenol on the three polymeric adsorbents were measured and correlated to a Freundlich isotherm. Adsorption enthalpy, adsorption Gibbs free energy, and adsorption entropy were calculated using thermodynamic function relationships. It was found that the adsorption enthalpy of phenol on PMVBU was almost twice that on PMVBA and PMVBC. Analysis of the adsorption mechanism suggested that hydrogen bonding was the primary driving force for phenol adsorbed on the adsorbents in cyclohexane, and multiple hydrogen bonding was involved for PMVBU with phenol. PMID- 17870086 TI - Crystal structure and DNA repair activities of the AP endonuclease from Leishmania major. AB - Apurinic/apyrimidinic endonucleases initiate the repair of abasic sites produced either spontaneously, from attack of bases by reactive oxygen species or as intermediates during base excision repair. The catalytic properties and crystal structure of Leishmania major apurinic/apyrimidinic endonuclease are described and compared with those of human APE1 and bacterial exonuclease III. The purified enzyme is shown to possess apurinic/apyrimidinic endonuclease activity of the same order as eukaryotic and prokaryotic counterparts and an equally robust 3' phosphodiesterase activity. Consistent with this, expression of the L. major endonuclease confers resistance to both methyl methane sulphonate and H2O2 in Escherichia coli repair-deficient mutants while expression of the human homologue only reverts methyl methane sulphonate sensitivity. Structural analyses and modelling of the enzyme-DNA complex demonstrates a high degree of conservation to previously characterized homologues, although subtle differences in the active site geometry might account for the high 3'-phosphodiesterase activity. Our results confirm that the L. major's enzyme is a key element in mediating repair of apurinic/apyrimidinic sites and 3'-blocked termini and therefore must play an important role in the survival of kinetoplastid parasites after exposure to the highly oxidative environment within the host macrophage. PMID- 17870087 TI - A switch in the mechanism of communication between the two DNA-binding sites in the SfiI restriction endonuclease. AB - While many Type II restriction enzymes are dimers with a single DNA-binding cleft between the subunits, SfiI is a tetramer of identical subunits. Two of its subunits (a dimeric unit) create one DNA-binding cleft, and the other two create a second cleft on the opposite side of the protein. The two clefts bind specific DNA cooperatively to give a complex of SfiI with two recognition sites. This complex is responsible for essentially all of the DNA-cleavage reactions by SfiI: virtually none is due to the complex with one site. The communication between the DNA-binding clefts was examined by disrupting one of the very few polar interactions in the otherwise hydrophobic interface between the dimeric units: a tyrosine hydroxyl was removed by mutation to phenylalanine. The mutant protein remained tetrameric in solution and could bind two DNA sites. But instead of being activated by binding two sites, like wild-type SfiI, it showed maximal activity when bound to a single site and had a lower activity when bound to two sites. This interaction across the dimer interface thus enforces in wild-type SfiI a cooperative transition between inactive and active states in both dimers, but without this interaction as in the mutant protein, a single dimer can undergo the transition to give a stable intermediate with one inactive dimer and one active dimer. PMID- 17870088 TI - Evidence that human histidine triad nucleotide binding protein 3 (Hint3) is a distinct branch of the histidine triad (HIT) superfamily. AB - Human Hint3 (hHint3) has been classified as a member of the histidine triad nucleotide (Hint) binding protein subfamily. While Hint1 is ubiquitously expressed by both eukaryotes and prokaryotes, Hint3 is found only in eukaryotes. Previously, our laboratory has characterized and compared the aminoacyl-adenylate and nucleoside phosphoramidate hydrolase activity of hHint1 and Escherichia coli hinT. In this study, hHint3-1(Ala36) and its single nucleotide polymorphism, hHint3-2 (A36G variant), were cloned, overexpressed, and purified. Steady-state kinetic studies with a synthetic fluorogenic indolepropinoic acyl-adenylate (AIPA) and with a series of fluorogenic tryptamine nucleoside phosphoramidates revealed that hHint3-1 and hHint3-2 are adenylate and phosphoramidate hydrolases with apparent second-order rate constants (kcat/Km) ranging from 10(2) to 10(6) s(-1) M(-1). Unlike hHint1, hHint3-1 and hHint3-2 prefer AIPA over tryptamine adenosine phosphoramidate by factors of 33- and 16-fold, respectively. In general, hHint3s hydrolyze phosphoramidate 370- to 2000-fold less efficiently than hHint1. Substitution of the potential active-site nucleophile, His145, by Ala was shown to abolish the adenylate and phosphoramidate hydrolase activity for hHint3-1. However, 0.2-0.4% residual activity was observed for the H145A mutant of hHint3-2. Both hHint3-1 and hHint3-2 were found to hydrolyze lysyl-adenylate generated by human lysyl-tRNA synthetase (hLysRS) by proceeding through an adenylated protein intermediate. hLysRS-dependent labeling of hHint3-1 and hHint3 2 was found to depend on His145, which aligns with the His112 of the Hint1 active site. The extent of active-site His145-AMP labeling was shown to be similar to His112-AMP labeling of hHint1. In contrast to all previously characterized members of the histidine triad superfamily, which have been shown to exist exclusively as homodimers, wild type and the H145A of hHint3-1 were found to exist across a range of multimeric states, from dimers to octamers and even larger oligomers, while wild type and the H145A of hHint3-2 exist predominantly in a monomeric state. The differences in oligomeric state may be important in vivo, because unlike tetracysteine-tagged Hint1, which was found along linear arrays exclusively in the cytoplasm in transfected HeLa cells, tagged Hint3-1 and Hint3-2 were found as aggregates both in the cytosol and in the nucleus. Taken together, these results imply that while Hint3 and Hint1 prefer aminoacyl adenylates as substrates and catalytically interact with aminoacyl-tRNA synthetases, the significant differences in phosphoramidase activity, oligomeric state, and cellular localization suggest that Hint3s should be placed in a distinct branch of the histidine triad superfamily. PMID- 17870090 TI - Structural insight into the constitutive repression function of the nuclear receptor Rev-erbbeta. AB - The Rev-erb family is an orphan nuclear receptor acting as a negative regulator of transcription. Rev-erbalpha and Rev-erbbeta are crucial components of the circadian clock and involved in various lipid homeostasis. They are unique nuclear receptors that lack the activation function 2 helix (AF2-helix) required for ligand-dependent activation by other members of nuclear receptors. Here, we report the crystal structure of Rev-erbbeta (NR1D2) in a dimeric arrangement. The putative ligand-binding pocket (LBP) of Rev-erbbeta is filled with bulky hydrophobic residues resulting in a residual cavity size that is too small to allow binding of any known ligand molecules. However, an alternative conformation of the putative LBP observed in another crystal form suggests the flexibility of this region. The kinked conformation of helix H11 allows helix H11 to bend toward helix H3 over the putative ligand binding pocket by filling and closing the cavity with its side-chains. In the absence of the AF2-helix and a cognate ligand, Rev-erbbeta appears to stabilize the hydrophobic cluster in the putative ligand binding pocket and provide a structural platform for co-repressor binding by adopting the unique geometry of helix H11, a suitable conformation for the constitutive repression activity. PMID- 17870089 TI - Substrate modulation of enzyme activity in the herpesvirus protease family. AB - The herpesvirus proteases are an example in which allosteric regulation of an enzyme activity is achieved through the formation of quaternary structure. Here, we report a 1.7 A resolution structure of Kaposi's sarcoma-associated herpesvirus protease in complex with a hexapeptide transition state analogue that stabilizes the dimeric state of the enzyme. Extended substrate binding sites are induced upon peptide binding. In particular, 104 A2 of surface are buried in the newly formed S4 pocket when tyrosine binds at this site. The peptide inhibitor also induces a rearrangement of residues that stabilizes the oxyanion hole and the dimer interface. Concomitant with the structural changes, an increase in catalytic efficiency of the enzyme results upon extended substrate binding. A nearly 20-fold increase in kcat/KM results upon extending the peptide substrate from a tetrapeptide to a hexapeptide exclusively due to a KM effect. This suggests that the mechanism by which herpesvirus proteases achieve their high specificity is by using extended substrates to modulate both the structure and activity of the enzyme. PMID- 17870091 TI - Crystal structure of family 5 uracil-DNA glycosylase bound to DNA. AB - Uracil-DNA glycosylase (UDG) removes uracil generated by the deamination of cytosine or misincorporation of deoxyuridine monophosphate. Within the UDG superfamily, a fifth UDG family lacks a polar residue in the active-site motif, which mediates the hydrolysis of the glycosidic bond by activation of a water molecule in UDG families 1-4. We have determined the crystal structure of a novel family 5 UDG from Thermus thermophilus HB8 complexed with DNA containing an abasic site. The active-site structure suggests this enzyme uses both steric force and water activation for its excision reaction. A conserved asparagine residue acts as a ligand to the catalytic water molecule. The structure also implies that another water molecule acts as a barrier during substrate recognition. Based on no significant open-closed conformational change upon binding to DNA, we propose a "slide-in" mechanism for initial damage recognition. PMID- 17870092 TI - The DNA maturation domain of gpA, the DNA packaging motor protein of bacteriophage lambda, contains an ATPase site associated with endonuclease activity. AB - Terminase enzymes are common to double-stranded DNA (dsDNA) viruses and are responsible for packaging viral DNA into the confines of an empty capsid shell. In bacteriophage lambda the catalytic terminase subunit is gpA, which is responsible for maturation of the genome end prior to packaging and subsequent translocation of the matured DNA into the capsid. DNA packaging requires an ATPase catalytic site situated in the N terminus of the protein. A second ATPase catalytic site associated with the DNA maturation activities of the protein has been proposed; however, direct demonstration of this putative second site is lacking. Here we describe biochemical studies that define protease-resistant peptides of gpA and expression of these putative domains in Escherichia coli. Biochemical characterization of gpA-DeltaN179, a construct in which the N terminal 179 residues of gpA have been deleted, indicates that this protein encompasses the DNA maturation domain of gpA. The construct is folded, soluble and possesses an ATP-dependent nuclease activity. Moreover, the construct binds and hydrolyzes ATP despite the fact that the DNA packaging ATPase site in the N terminus of gpA has been deleted. Mutation of lysine 497, which alters the conserved lysine in a predicted Walker A "P-loop" sequence, does not affect ATP binding but severely impairs ATP hydrolysis. Further, this mutation abrogates the ATP-dependent nuclease activity of the protein. These studies provide direct evidence for the elusive nucleotide-binding site in gpA that is directly associated with the DNA maturation activity of the protein. The implications of these results with respect to the two roles of the terminase holoenzyme, DNA maturation and DNA packaging, are discussed. PMID- 17870093 TI - Structure-based mechanism of ligand binding for periplasmic solute-binding protein of the Bug family. AB - Bug proteins form a large family of periplasmic solute-binding proteins well represented in beta-proteobacteria. They adopt a characteristic Venus flytrap fold with two globular domains bisected by a ligand-binding cleft. The structures of two liganded Bug proteins have revealed that the family is specific for carboxylated solutes, with a characteristic mode of binding involving two highly conserved beta strand-beta turn-alpha helix motifs originating from each domain. These two motifs form hydrogen bonds with a carboxylate group of the ligand, both directly and via conserved water molecules, and have thus been termed the carboxylate pincers. In both crystallized Bug proteins, the ligands were found enclosed between the two domains and inaccessible to solvent, suggesting an inter domain hinge-bending motion upon ligand binding. We report here the first structures of an open, unliganded Bug protein and of the same protein with a citrate ion bound in the open cavity. One of the ligand carboxylate groups is bound to one half of the carboxylate pincers by the beta strand-beta turn-alpha helix motif from domain 1, and the citrate ion forms several additional interactions with domain 1. The ligand is accessible to solvent and has very few contacts with domain 2. In this open, liganded structure, the second part of the carboxylate pincers originating from domain 2 is not stabilized by ligand binding, and a loop replaces the beta turn. In the unliganded structure, both motifs of the carboxylate pincers are highly mobile, and neither of the two beta turns is formed. Thus, ligand recognition is performed by domain 1, with the carboxylate group serving as an initial anchoring point. Stabilization of the closed conformation requires proper interactions to be established with domain 2, and thus domain 2 discriminates between productively and non-productively bound ligands. PMID- 17870094 TI - Intravenous mitoxantrone and cyclophosphamide as second-line therapy in multiple sclerosis: an open-label comparative study of efficacy and safety. AB - The study's aim was to compare the efficacy and safety of intravenous cyclophosphamide (CTX) and mitoxantrone (MITO) as second-line therapy in a clinical sample of active relapsing-remitting (RR) or secondary-progressive (SP) multiple sclerosis subjects. MITO was administered at a dosage of 8 mg/m(2) monthly for 3 months, then every 3 months, until a dosage of 120 mg/m(2) was reached. CTX was administered at a dosage of 700 mg/m(2) monthly for 12 months, then bimonthly for another 24 months. We used the Kaplan-Meier curves to assess time to the first relapse in RR and SP patients with relapses, and time to progression on the Expanded Disability Status Scale (EDSS) in all the patients. MRI was assessed at baseline and after 12 months. Moreover, side effects were recorded. Seventy-five patients received MITO (31 RR, 44 SP) and 78 CTX (15 RR, 63 SP). The two groups differ only in terms of a significantly higher proportion of RR patients in the MITO group. After a mean follow-up of 3.6 years there was no significant difference in terms of time to the first relapse (MITO 2.6 years, CTX 2.5 years; p=0.50), whereas time to disease progression was slightly shorter in MITO than in CTX group (MITO 3.8 years, CTX 3.6 years; p=0.04). After 12 months of treatment, active MRI scans were reduced by 69% in MITO and 63% in CTX patients (p=0.10). Discontinuation due to side effects was more frequent in CTX patients. However, the overall tolerability profile was acceptable in both groups. PMID- 17870102 TI - WITHDRAWN. AB - The publisher regrets that this article is an accidental duplication of an article that has already been published in J. Urol., 176 (2006) 1912-1913, doi:10.1016/j.juro.2007.07.053. The duplicate article has therefore been withdrawn. PMID- 17870105 TI - Re: The relationship between varicoceles and obesity. PMID- 17870106 TI - Re: Bilateral testicular germ cell tumors in Turkey: increase in incidence in last decade and evaluation of risk factors in 30 patients. PMID- 17870107 TI - Diabetic urethropathy compounds the effects of diabetic cystopathy. AB - PURPOSE: The effects of short-term and long-term diabetes mellitus on urethral function were investigated to determine the contribution of urethral dysfunction to diabetes mellitus voiding dysfunction. MATERIALS AND METHODS: Isovolumetric bladder pressure, urethral perfusion pressure and external urethral sphincter electromyography were measured in urethane anesthetized, female Sprague-Dawley rats (Charles River Laboratories, Wilmington, Massachusetts) 5 or 10 weeks after streptozotocin induced diabetes mellitus. Urethral responses to serial administration of the skeletal muscle blocker alpha-bungarotoxin, the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine and the alpha-adrenergic agonist L-phenylephrine were determined in diabetes mellitus and age matched controls. RESULTS: Peak bladder pressures and contraction amplitudes were significantly decreased in diabetes mellitus rats. Detrusor-sphincter dyssynergia occurred in approximately 30% of diabetes mellitus rats but never in controls. Alpha-Bungarotoxin caused a greater decrease in baseline urethral perfusion pressure in diabetes mellitus rats than in controls (approximately 40% vs approximately 15%). Bladder contraction associated urethral smooth muscle relaxation amplitudes were significantly less in diabetes mellitus rats than in controls. N(omega)-nitro-L-arginine significantly suppressed urethral relaxation in controls but not in diabetes mellitus rats. L-phenylephrine significantly increased baseline urethral perfusion pressure in diabetes mellitus rats but not in controls. The unassociated conditions of insensitivity to N-nitro-L-arginine and hypersensitivity to L-phenylephrine were more common in 10-week diabetes mellitus rats than in control rats. CONCLUSIONS: Diabetes mellitus induced urethropathy is characterized by external urethral sphincter dysfunction, decreased urethral smooth muscle relaxation and nitric oxide responsiveness, and increased urethral smooth muscle responsiveness to alpha(1)-adrenergic agonists. These changes increase outlet resistance and, thereby, decrease voiding efficiency. This exacerbates voiding dysfunction, creating a vicious cycle of progressive lower urinary tract damage and dysfunction. Early intervention targeting outlet resistance may be indicated. PMID- 17870108 TI - Antimuscarinic drug inhibits detrusor overactivity induced by topical application of prostaglandin E2 to the urethra with a decrease in urethral pressure. AB - PURPOSE: Antimuscarinic drugs increase bladder capacity without prominent side effects such as urinary retention even when administered to patients with mild to moderate bladder outlet obstruction. Some mechanisms might exist in the urethra to compensate for the emptying function of the detrusor after the administration of antimuscarinic drugs. We investigated the influence of the antimuscarinic drug propiverine (Taiho Pharmaceutical, Tokyo, Japan) on urethral function. MATERIALS AND METHODS: Urethral pressure and rhythmic bladder pressure were simultaneously monitored in urethane anesthetized female Sprague-Dawley rats. Prostaglandin E(2) was continuously administered intravesically or intraurethrally to induce detrusor overactivity. To eliminate the influence of bladder activity and monitor urethral baseline pressure isovolumetric pressure of the urethra was then recorded after cystectomy and ligation of the external urethral meatus. Furthermore, in vitro contractile responses of the urethral circular smooth muscle to field stimulation were examined in the presence of propiverine, tamsulosin (Taiho Pharmaceutical), verapamil, omega-conotoxin and atropine (Sigma). RESULTS: Intravesical or intraurethral administration of prostaglandin E(2) significantly decreased the bladder contraction interval by 10.7% and 36.0%, respectively. Intra-arterial administration of 2 x 10(2) nM/kg propiverine significantly increased the bladder contraction interval in rats receiving intraurethral prostaglandin E(2) by 81.8% but it had no marked effect on rats receiving intravesical prostaglandin E(2). Significant decreases in urethral baseline pressure were found after propiverine administration. Field stimulation induced contraction was inhibited by propiverine and verapamil but not by tamsulosin, omega-conotoxin or atropine. CONCLUSIONS: These results suggest that the inhibitory effects of propiverine are more prominent in rats with detrusor overactivity induced by intraurethral prostaglandin E(2) than by intravesical prostaglandin E(2). Propiverine may compensate for detrusor function by decreasing urethral resistance in the voiding phase. PMID- 17870109 TI - Aldose reductase inhibitor ONO-2235 restores the alterations of bladder nerve growth factor and neurotrophin receptor p75 genetic expression in streptozotocin induced diabetic rats. AB - PURPOSE: We assessed the treatment effect of the aldose reductase inhibitor ONO 2235 (China Chemical and Pharmaceutical, Taipei, Taiwan) on diabetes associated alterations in bladder nerve growth factor and the nerve growth factor neurotrophin receptor p75 mRNA expressions using the streptozotocin (Sigma) induced diabetic rat model. MATERIALS AND METHODS: Male Wistar rats were divided into 3 groups, including group 1--vehicle treated normal rats, group 2--vehicle treated 9-week streptozotocin diabetic rats and group 3--ONO-2235 treated 9-week streptozotocin diabetic rats. In vivo cystometry was performed using anesthesia. Bladder nerve growth factor levels were measured by enzyme linked immunosorbent assay. Expression of the mRNA encoding nerve growth factor and neurotrophin receptor p75 in the rat bladder was studied using reverse transcriptase polymerase chain reaction. RESULTS: Cystometry showed increased bladder capacity and decreased emptying function in diabetic rats. ONO-2235 treatment improved voiding volume, voiding fraction and residual volume. The nerve growth factor concentration in streptozotocin induced diabetic rat bladders was significantly lower than the control level in 8 experiments each (mean +/- SEM 45.78 +/- 4.36 and 96.44 +/- 8.73 pg/microg protein, respectively, p <0.01). The mRNA expression of bladder nerve growth factor and neurotrophin receptor p75 in diabetic rats was significantly decreased compared to that in controls in 8 experiments each (p <0.01 and <0.001, respectively). Treatment with ONO-2235 did not significantly change the blood sugar level in diabetic rats. However, administration of the drug significantly increased the bladder nerve growth factor concentration as well as nerve growth factor mRNA and neurotrophin receptor p75 mRNA expression to normal levels in 8 experiments each (p <0.01, <0.01 and <0.001, respectively). CONCLUSIONS: ONO-2235 improved bladder emptying function and restored the decreased genetic expression of bladder nerve growth factor and neurotrophin receptor p75 in 9-week streptozotocin induced diabetic rats, indicating involvement of the sorbitol pathway in the genetic down-regulations of nerve growth factor and p75(NTR) during diabetic cystopathy. PMID- 17870110 TI - Real-time intraoperative ureteral guidance using invisible near-infrared fluorescence. AB - PURPOSE: Invisible near-infrared light is safe and it penetrates relatively deeply through tissue and blood without altering the surgical field. Our hypothesis was that near-infrared fluorescence imaging would enable visualization of the ureteral anatomy and flow intraoperatively and in real time. MATERIALS AND METHODS: CW800-CA (LI-COR, Lincoln, Nebraska), the carboxylic acid form of near infrared fluorophore IRDye 800CW, was injected intravenously, and its renal clearance kinetics and imaging performance were quantified in 350 gm rats and 35 kg pigs. High performance liquid chromatography and electrospray time-of-flight mass spectrometry were used to characterize CW800-CA metabolism in urine. The clinically available near-infrared fluorophore indocyanine green was also used via retrograde injection into the ureter. Using the 2 near-infrared fluorophores the ureters were imaged under the conditions of steady state, intraluminal foreign bodies and injury. RESULTS: In rat models the highest signal-to background ratio for visualization occurred after intravenous injection of 7.5 microg/kg CW800-CA with values of 4.0 or greater and 2.3 or greater at 10 and 30 minutes, respectively. In pig models 7.5 microg/kg CW800-CA clearly visualized the normal ureter and intraluminal foreign bodies as small as 2.5 mm in diameter. Retrograde injection of 10 microM indocyanine green also permitted the detection of normal ureter and pinpointed urine leakage caused by injury. Electrospray time of-flight mass spectrometry, and absorbance and fluorescence spectral analysis confirmed that the fluorescent material in urine was chemically identical to CW800-CA. CONCLUSIONS: A convenient intravenous injection of CW800-CA or direct injection of indocyanine green permits high sensitivity visualization of the ureters under steady state and abnormal conditions using invisible light. PMID- 17870111 TI - Dietary oxalate and calcium oxalate nephrolithiasis. AB - PURPOSE: Patients with calcium oxalate kidney stones are advised to decrease the consumption of foods that contain oxalate. We hypothesized that a cutback in dietary oxalate would lead to a decrease in the urinary excretion of oxalate and decreased stone recurrence. We tested the hypothesis in an animal model of calcium oxalate nephrolithiasis. MATERIALS AND METHODS: Hydroxy-L-proline (5%), a precursor of oxalate found in collagenous foods, was given with rat chow to male Sprague-Dawley rats. After 42 days rats in group 1 continued on hydroxy-L proline, while those in group 2 were given chow without added hydroxy-L-proline for the next 21 days. Food and water consumption as well as weight were monitored regularly. Once weekly urine was collected and analyzed for creatinine, calcium, oxalate, lactate dehydrogenase, 8-isoprostane and H(2)O(2). Urinary pH and crystalluria were monitored. Rats were sacrificed at 28, 42 and 63 days, respectively. Renal tissue was examined for crystal deposition by light microscopy. RESULTS: Rats receiving hydroxy-L-proline showed hyperoxaluria, calcium oxalate crystalluria and nephrolithiasis, and by day 42 all contained renal calcium oxalate crystal deposits. Urinary excretion of lactate dehydrogenase, 8-isoprostane and H(2)O(2) increased significantly. After hydroxy L-proline was discontinued in group 2 there was a significant decrease in urinary oxalate, 8-isoprostane and H(2)O(2). Half of the group 2 rats appeared to be crystal-free. CONCLUSIONS: Dietary sources of oxalate can induce hyperoxaluria and crystal deposition in the kidneys with associated degradation in renal biology. Eliminating oxalate from the diet decreases not only urinary oxalate, but also calcium oxalate crystal deposits in the kidneys and improves their function. PMID- 17870112 TI - Variability of Oxalobacter formigenes and oxalate in stool samples. AB - PURPOSE: The intestinal organism Oxalobacter formigenes is unique in using oxalate as its primary carbon and energy source. Intestinal colonization with O. formigenes may have clinical significance by decreasing intestinal oxalate and its absorption, thereby influencing the concentration of oxalate in plasma and urine, and the development of calcium oxalate stone disease. Because the oxalate content of the diet varies considerably, we hypothesized that the number of O. formigenes and amount of oxalate would vary in feces. MATERIALS AND METHODS: To enumerate the number of O. formigenes in feces an accurate and reproducible real time polymerase chain reaction assay was developed to quantify O. formigenes DNA. Stool samples were obtained from 10 colonized individuals to determine the levels of O. formigenes by this assay and the oxalate content by ion chromatography. RESULTS: Concentrations of O. formigenes ranged from lower than the limit of detection of 5 x 10(3) to 1.04 x 10(9) cells per gm stool. The total oxalate content of stool samples varied from 0.1 to 1.8 mg/gm and fecal water oxalate varied from 60 to 600 microM. All parameters measured varied within each stool collection, among stool collections on different days and among individuals. Notably in 7 of 10 individuals at least 1 stool sample contained no detectable O. formigenes. In addition, 7 of 10 subjects had a fecal colonization of less than 4 x 10(4) per gm stool. CONCLUSIONS: This study demonstrates that there is intrastool and interstool sample variability in the amount of O. formigenes measured by real-time polymerase chain reaction that did not correlate with the quantity of oxalate in stool. Most subjects had a fecal colonization of less than 4 x 10(4) per gm stool. PMID- 17870113 TI - Viral infections and lower urinary tract symptoms in the third national health and nutrition examination survey. AB - PURPOSE: Previous epidemiological studies described suggestive positive associations between sexually transmitted infections, particularly gonorrhea and human immunodeficiency virus infection, and lower urinary tract symptoms. To our knowledge no groups have investigated other infections, such as human papillomavirus type 16, herpes simplex virus type 2, cytomegalovirus, human herpesvirus type 8, herpes simplex type 1, and hepatitis B and C virus infection, in relation to lower urinary tract symptoms. Therefore, we examined each of these associations in the Third National Health and Nutrition Examination Survey. MATERIALS AND METHODS: The Third National Health and Nutrition Examination Survey is a representative, cross-sectional survey of the population in the United States that was done between 1988 and 1994. Each participant provided a blood sample and completed a computer assisted interview including questions on lower urinary tract symptoms (nocturia, incomplete emptying, hesitancy and weak stream). Blood samples were tested for IgG antibodies against each virus. RESULTS: In younger men (ages 30 to 49 years) positive associations were observed between cytomegalovirus, human herpesvirus type 8, herpes simplex virus type 1, and hepatitis B and C virus antibody seropositivity, and lower urinary tract symptoms. In 50 to 59-year-old men positive associations were observed between human papillomavirus type 16, herpes simplex virus type 2, cytomegalovirus, human herpesvirus type 8 and hepatitis C virus antibody seropositivity and lower urinary tract symptoms. In men 60 years or older only a slight, nonsignificant positive association was observed between cytomegalovirus antibody seropositivity and lower urinary tract symptoms. CONCLUSIONS: In this cross-sectional survey of American men suggestive positive associations were observed between several viral infections and lower urinary tract symptoms, primarily in 30 to 59-year-old men. These findings provide interesting hypotheses and preliminary evidence for future etiological studies of infections and lower urinary tract symptoms. PMID- 17870114 TI - Effect of alpha1-adrenoceptor antagonist exposure on prostate cancer incidence: an observational cohort study. AB - PURPOSE: The quinazoline based alpha1-adrenoceptor antagonists doxazosin and terazosin suppress prostate tumor growth via the induction of apoptosis and decrease in tissue vascularity. To assess the effect of alpha1-blocker exposure on the incidence of prostate cancer we performed an exploratory, observational cohort study. MATERIALS AND METHODS: The medical records of all male patients enrolled at Lexington Veterans Affairs Medical Center were searched to identify men treated with quinazoline based alpha1-adrenoreceptor antagonists between January 1, 1998 and December 31, 2002 for hypertension and/or benign prostatic enlargement. Medical records were subsequently linked to the Markey Cancer Center Kentucky Cancer Registry, a statewide population based central cancer registry that is part of the National Cancer Institute Surveillance, Epidemiology and End Results Program, to identify all incident prostate cancer cases diagnosed. All newly diagnosed prostate cancer cases unexposed to alpha1-adrenoreceptor antagonists in the total male Veterans Affairs population during this period were also identified from the Kentucky Cancer Registry database. Measures of disease incidence, relative risk and attributable risk were calculated to compare the risk of prostate cancer in alpha1-blocker exposed vs unexposed men. Kaplan-Meier curves and Cox regression models were used to compare overall survival between alpha1-blocker exposed and unexposed prostate cancer cases. RESULTS: Our analysis revealed a cumulative incidence of 1.65% in alpha1-blocker exposed men compared to 2.41% in the unexposed group. These data yielded an unadjusted RR of 0.683 (95% CI 0.532, 0.876) and a risk difference of -0.0076, indicating that 7.6 fewer prostate cancer cases developed per 1,000 exposed men. Thus, exposure to quinazoline alpha1-blockers may have prevented 32 prostate cancer cases among the 4,070 treated men during the study period. Therefore, men exposed to quinazoline alpha1-adrenoceptor antagonists were at 1.46 times lower RR and 31.7% lower attributable risk for prostate cancer than unexposed men. There was no association between alpha1-adrenoceptor antagonist exposure and overall survival. CONCLUSIONS: These data suggest that exposure to quinazoline based alpha1 adrenoceptor antagonists significantly decreases the incidence of prostate cancer. This evidence suggests that the apoptotic and anti-angiogenic effects of these drugs may prevent the development of prostate cancer. PMID- 17870115 TI - Multidrug resistance in a urothelial cancer cell line after 3, 1-hour exposures to mitomycin C. AB - PURPOSE: The development of multidrug resistance is a problem in chemotherapy for many tumors. In vitro models of multidrug resistance require adapted cell strains that are conventionally produced from parental lines by chronic low dose drug exposure. Because adjunctive intravesical chemotherapy for superficial bladder cancer uses short courses of high dose treatment, we investigated whether such exposure of the RT112 cell line (Catalogue No. ACC 418, Deutsche Sammlung von Mikroorganismen und Zellkulturen, Braunschweig, Germany) to mitomycin C, which is a common intravesical agent, would elicit multidrug resistance. MATERIALS AND METHODS: Three 1-hour exposures to graded concentrations were done at 3-week intervals. The highest mitomycin C concentrations permitting recovery in cultures and, therefore, available for examination were 3.13 and 1.06 microg/ml. Cross resistance to epirubicin in surviving cultures was visualized by confocal microscopy and quantified by MTT residual viable biomass assay. Spheroids were made by the agarose technique and exposed to high dose mitomycin C to assess the probability that the relevant concentrations might be found clinically in some cell layers of a superficial lesion. RESULTS: Resistance was induced by 3 short drug exposures. The evidence for this was functional (MTT assay) and by intracellular localization. Toxicity to an alternative multidrug resistance class drug was lowered in surviving clones and nuclear exclusion of the drug was noted. Spheroid experiments showed sharp gradients of incorporated drug across the outermost layers of cells, suggesting that a proportion of cells in clinical superficial bladder cancer would be exposed to drug at concentrations that generated the resistant clones in these experiments. CONCLUSIONS: We report multidrug resistance induction using 2 independent methodologies. The results have implications for the development of experimental models and the likelihood of resistance resulting from clinical regimens. Brief exposure can elicit detectable resistance. It is arguable that selective rather than instructive mechanisms are involved, and the levels of drug required are likely to exist in a superficial transitional cell carcinoma frond exposed at its surface to high drug concentrations. PMID- 17870116 TI - Bacillus Calmette-Guerin inhibits apoptosis in human urothelial carcinoma cell lines in response to cytotoxic injury. AB - PURPOSE: By inducing cell cycle arrest at the G1/S transition bacillus Calmette Guerin has been shown to have a direct antiproliferative effect on urothelial carcinoma cell lines. In other systems cell cycle arrest has been shown to confer a relative state of apoptotic resistance. We assessed the effect of bacillus Calmette-Guerin on the susceptibility of urothelial carcinoma cells to apoptotic stimuli. MATERIALS AND METHODS: The human UC cell lines T24 and 253J (American Type Cell Culture, Rockville, Maryland) were used to evaluate the effect of bacillus Calmette-Guerin or antibody mediated alpha5beta1cross-linking on apoptosis and apoptotic sensitivity. Following treatment baseline apoptosis and the response to the apoptotic inducing agent camptothecin was evaluated using assays for caspase 3 activation and DNA fragmentation. Pharmacological blockade of signaling pathways known to be activated in response to bacillus Calmette Guerin/alpha5beta1 cross-linking was used to assess the role of these pathways in the bacillus Calmette-Guerin apoptotic response. A final series of experiments used the MTT assay to study the impact of bacillus Calmette-Guerin pretreatment on the cytotoxicity of the antineoplastic agent mitomycin C. RESULTS: Treatment with bacillus Calmette-Guerin failed to induce apoptosis, as measured by caspase 3 activation or DNA laddering. Bacillus Calmette-Guerin pretreatment significantly inhibited the induction of apoptosis in response to camptothecin. These effects were reproduced by antibody mediated cross-linking of alpha5beta1 integrin. Pharmacological inhibition of nuclear factor kappaB and/or AP1 signaling pathways reversed the anti-apoptotic effect of bacillus Calmette Guerin. Mitomycin C cytotoxicity was significantly decreased by bacillus Calmette Guerin pretreatment. CONCLUSIONS: Bacillus Calmette-Guerin exerts a direct anti apoptotic effect on human urothelial carcinoma cell lines. The ability of antibody mediated cross-linking to reproduce the effect and the ability of signal transduction inhibitors to block it are consistent with a mechanism involving integrin mediated signaling. Apoptotic resistance represents a therapeutic target for modulating the response to bacillus Calmette-Guerin and it may have clinical implications in the sequencing of intravesical therapies. PMID- 17870117 TI - Microscopic hematuria attributed to retroaortic left renal vein. PMID- 17870118 TI - Renal cell carcinoma and other concurrent renal neoplasms. PMID- 17870119 TI - Urological counseling and followup in pediatric tuberous sclerosis complex. AB - PURPOSE: We review our experience with renal manifestations in pediatric patients with the tuberous sclerosis complex, and offer recommendations for urological counseling, followup and treatment of these patients. MATERIALS AND METHODS: We reviewed clinical notes on 41 patients with the tuberous sclerosis complex followed at our institution from childhood. Patient data were gathered in a database focusing on renal involvement. The latter was assessed by periodic clinical evaluations and ultrasound. The risk of renal involvement was evaluated in relation to patient age, genotypic pattern and number of extrarenal manifestations. RESULTS: Overall, 15 patients (36.6%) had renal involvement. The latter increased with age and was more common in cases with TSC2 genotypic pattern or multiple extrarenal manifestations. Angiomyolipomas were the most common lesions (11 patients), followed by renal cysts (2) and polycystic kidney disease (2). Cystic lesions were the most common in patients younger than 16 years. Renal failure developed in the 2 patients with polycystic kidney disease by the 2nd decade of life. Overall, treatment was required in 2 cases of symptomatic angiomyolipoma. Both patients were female, and had multiple extrarenal manifestations and bilateral renal involvement. One patient underwent open surgery at age 21.3 years and 1 underwent radiological embolization at age 23.4 years. CONCLUSIONS: Pediatric patients with the tuberous sclerosis complex should undergo urological evaluation and followup. Although most of the lesions remain silent during childhood, the incidence of renal involvement increases with age. The need for treatment is highest in females with multiple extrarenal manifestations and bilateral renal involvement. PMID- 17870120 TI - Nomogram of fetal renal growth expressed in length and parenchymal area derived from ultrasound images. AB - PURPOSE: We constructed nomograms of fetal renal length and parenchymal area derived from ultrasound images to develop a standard for normal fetal renal growth. MATERIALS AND METHODS: Longitudinal and transverse ultrasound renal images from 216 normal fetuses (16 to 41 weeks of gestation) were evaluated to construct growth charts. We measured the parenchymal area as well as the longitudinal and transverse lengths of each kidney using computer software for image analysis. Data were separately plotted as a mean +/- 2 SD determined by polynomial regression analysis. RESULTS: Nomograms for a renal growth chart were constructed independently for the right and left fetal kidneys. No statistically significant difference was noted between the right and left renal measurements. The polynomial regression equations for the left renal longitudinal length and parenchymal area, respectively, were y = -0.0002x(3) + 0.0139x(2) - 0.2162 x 2.3929 (r(2) = 0.9842), and y = -0.0009x(3) + 0.0724x(2) - 1.5643 x 11.68 (r(2) = 0.9779). The longitudinal and transverse fetal renal growth curves displayed significant growth associated with gestational age (p <0.001). Our data on left longitudinal renal length exhibited an intermediate level compared to 2 published Western growth charts. However, statistical comparisons revealed the differences were partially, but not universally, significant. CONCLUSIONS: We present our nomogram of fetal renal growth expressed in length and parenchymal area. To our knowledge this is the first report of a fetal renal growth chart in Asia that includes the parenchymal area. This nomogram may serve as a valuable tool for evaluation of fetal renal growth. PMID- 17870121 TI - The effects of bladder neck incision on urodynamic abnormalities of children with posterior urethral valves. AB - PURPOSE: We evaluated the effects of simultaneous bladder neck incision and valve ablation on urodynamic abnormalities in patients with posterior urethral valves. MATERIALS AND METHODS: A total of 46 patients with posterior urethral valves entered our prospective study between 1998 and 2003. Group 1 consisted of 22 patients who underwent simultaneous valve ablation and bladder neck incision at the 6 o'clock position. Group 2 consisted of 24 age matched patients with comparable prognostic factors who underwent simple valve ablation. Trends in renal function tests, urodynamics and changes in the upper urinary tracts were evaluated throughout followup. RESULTS: Mean patient age at presentation was 1.6 years in group 1 and 1.8 years in group 2. Preoperatively, all patients in both groups had hypercontractile bladders and comparable high maximum voiding detrusor pressures. At the end of followup (mean 4.5 years) no patient in group 1 had bladder hypercontractility or detrusor overactivity, and the mean maximum voiding detrusor pressure was 53 +/- 15 cm H(2)O. In comparison, 9 patients in group 2 had bladder hypercontractility, 6 had detrusor overactivity and the mean maximum voiding detrusor pressure was 87 +/- 45 cm H(2)O (p <0.01). Myogenic bladder failure developed in 5 patients in group 2. The number of patients requiring anticholinergic medication and the duration of treatment were also significantly higher in group 2 compared to group 1. CONCLUSIONS: Valve ablation with bladder neck incision may result in better bladder urodynamic function in comparison to simple valve ablation. However, long-term studies with followup through puberty are required to evaluate the final effects on renal function. PMID- 17870122 TI - Pediatric robot assisted retroperitoneoscopic pyeloplasty: a 5-year experience. AB - PURPOSE: We report our 5-year experience with retroperitoneoscopic robot assisted pyeloplasty for the treatment of ureteropelvic junction obstruction in children using the da Vinci Surgical System. MATERIALS AND METHODS: A total of 65 children (median age 7.9 years, range 1.7 to 17.1) underwent 67 robot assisted retroperitoneoscopic pyeloplasties with the da Vinci Surgical System between 2002 and 2006. Operative data were sampled prospectively, while outcome data were collected from chart review. Retroperitoneal access was modified from standard retroperitoneoscopic access due to the limits of the camera arm movement. RESULTS: Median operative time was 143 minutes (range 93 to 300). Complications occurred in 12 of the 67 procedures (17.9%), with urinary tract infection observed in 2 cases, transient hematuria in 2, displaced Double-J catheter in 3 and postoperative temporary nephrostomy in 4. One case was converted to open surgery due to lack of space and limits in the movement of the camera arm. Four patients (6%) underwent repeat surgery due to a kinking ureter (2 patients), an overlooked aberrant vessel (1) and decreasing differential function on renography necessitating balloon dilation (1). In all other cases followup was uneventful. CONCLUSIONS: Robot assisted retroperitoneoscopic pyeloplasty gives more direct access to the ureteropelvic junction, allowing shorter operative times with results and complication rates comparable to transperitoneal robot assisted pyeloplasty, and laparoscopic and open procedures in children. PMID- 17870123 TI - Do holding exercises or antimuscarinics increase maximum voided volume in monosymptomatic nocturnal enuresis? A randomized controlled trial in children. AB - PURPOSE: We assessed prospectively the efficacy of holding exercises and/or antimuscarinics (oxybutynin chloride and placebo) for increasing maximum voided volume in prepubertal children with monosymptomatic nocturnal enuresis. MATERIALS AND METHODS: We randomly allocated 149 children to 5 groups, namely holding exercises with placebo (group A), holding exercises with oxybutynin (group B), placebo alone (group C), oxybutynin alone (group D) and alarm treatment (controls, group E). Maximum voided volume was the greatest voided volume from a 48-hour bladder diary, and holding exercise volume was the greatest volume produced with postponement of voiding after a fluid load, once daily for 4 days. Study medication, holding exercise procedures and alarm treatment were administered for 12 weeks. RESULTS: Holding exercises combined with placebo or oxybutynin significantly increased holding exercise volume and maximum voided volume, by 25% (p <0.001) and 21% (p <0.01), respectively, in group A, and by 43% (p <0.001) and 41% (p <0.001), respectively, in group B. Medication without holding exercises (groups C and D) did not increase holding exercise volume or maximum voided volume, and in these groups oxybutynin was not significantly superior to placebo. A borderline increase in holding exercise volume did not affect maximum voided volume in group E. Monosymptomatic nocturnal enuresis response was significantly lower with all 4 holding exercise volume modulating treatments (7%) compared to alarm therapy (73%). CONCLUSIONS: In the treatment of children with monosymptomatic nocturnal enuresis maximum voided volume can be increased significantly through holding exercises, but not with oxybutynin chloride alone. Compared to controls, increasing maximum voided volume had a minimal effect on monosymptomatic nocturnal enuresis. PMID- 17870124 TI - Is ureteroscopy first line treatment for pediatric stone disease? AB - PURPOSE: We report our current outcomes for ureteroscopic management of pediatric stone disease. MATERIALS AND METHODS: We carried out a retrospective review of all ureteroscopic procedures for kidney or ureteral calculi performed between 2001 and 2005. Stone location and size, preoperative and postoperative stenting, intraoperative dilation, use of ureteral access sheath, stone-free rates and complications were noted. RESULTS: A total of 100 patients (58% female, mean age 13.2 years) underwent 115 procedures. Stones were located in the renal pelvis in 6% of patients, upper pole in 10%, mid ureter in 11%, lower pole in 17%, proximal ureter in 19% and distal ureter in 37%. Mean stone size was 8.3 mm (median 7.0), with a mean of 1.5 stones per patient. Preoperative stenting was used in 54% of patients, and a stent was placed postoperatively in 76%. Ureteral coaxial dilators and ureteral access sheaths were used in 70% and 24% of patients, respectively. There were no major intraoperative complications, although 5 patients required stent placement for ureteral perforation or extravasation. One patient had a ureteral stricture requiring ureteral reimplantation. Mean followup was 10.1 months (median 2.6). Stone-free rate was 91% on followup ultrasound, abdominal radiography or computerized tomography. Seven patients required staged ureteroscopic procedures to achieve stone-free status. While the number of percutaneous nephrolithotomy and shock wave lithotripsy cases remained stable, the number of ureteroscopic cases increased 7-fold during this period. CONCLUSIONS: Improved ureteroscopic access to stones throughout the pediatric urinary tract and stone-free rates that are comparable to the adult population have led to the adoption of ureteroscopy as first line therapy in children at our institution. PMID- 17870125 TI - Extraosseous bone formation in the renal pelvis. AB - PURPOSE: We evaluated the frequency and features of extraosseous bone formation in the kidneys of patients undergoing percutaneous nephrolithotomy. MATERIALS AND METHODS: Percutaneous nephrolithotomy was performed in 621 patients at our institution between 1997 and 2006. In 21 cases metaplastic bone arising from the urothelium was observed. Clinical, radiographic and histopathological features of this group were studied in detail. RESULTS: Patient age ranged from 7 to 40 years (median 11). Extraosseous bone formation was identified in 7 right (33%) and 14 left (67%) kidneys. In all cases extraosseous bone was identified at the angle of the pelvis and ureter, just proximal to the ureteropelvic junction. The typical radiographic appearance of a radiopaque eccentric halo surrounding an area of lesser radiological density connected with the urothelium was seen in 10 of 13 radiographs (77%). Histopathological evaluation showed well formed trabecular bone with surface osteoblastic activity, areas of intratrabecular adipose bone marrow and hematopoietic cells in 5 cases (24%); woven bone intimately related to trabecular bone with scattered hematopoietic cells in 14 (67%); and entirely woven bone with associated mineral deposits and prominent fibroblastic proliferation in 2 (10%). CONCLUSIONS: Although rarely reported in the literature, metaplastic bone formation in the renal pelvis was seen relatively frequently in our patient population. The pathogenesis of this phenomenon is not clearly understood. Recognition of extraosseous bone is important, since it has implications for management and prognosis. In-depth studies of this phenomenon are required to arrive at any conclusions regarding its etiology. PMID- 17870126 TI - Assessment of the core learning objectives curriculum for the urology clerkship. AB - PURPOSE: The traditional approach to the surgical clerkship has limitations, including variability of clinical exposure. To optimize student education we developed and introduced the core learning objectives curriculum, which is designed to allow students freedom to direct their learning and focus on core concepts. We performed a prospective, randomized, controlled study to compare the efficacy of core learning objectives vs traditional curricula through objective and subjective measures. MATERIALS AND METHODS: Medical students were randomly assigned to the core learning objectives or traditional curricula during the 2 week urology clerkship. Faculty was blinded to student assignment. Upon rotation completion all students were given a 20-question multiple choice examination covering basic urology concepts. In addition, students completed a questionnaire addressing subjective clerkship satisfaction, comprising 15 questions. RESULTS: Between June 2005 and January 2007, 10 core learning objectives students and 10 traditional students completed the urology clerkship. The average +/- SEM multiple choice examination score was 12.1 +/- 0.87 and 9.8 +/- 0.59 for students assigned to the core learning objectives and traditional curricula, respectively (p <0.05). Subjective scores were higher in the core learning objectives cohort, although this result did not attain statistical significance (124.9 +/- 3.72 vs 114.3 +/- 4.96, p = 0.1). Core learning objectives students reported higher satisfaction in all 15 assessed subjective end points. CONCLUSIONS: Our experience suggests that the core learning objectives model may be an effective educational tool to help students achieve a broad and directed exposure to the core urological concepts. PMID- 17870127 TI - Differential adoption of laparoscopy by treatment indication. AB - PURPOSE: The diffusion of laparoscopic renal surgery has been gradual. While surgery for benign and malignant kidney disease is usually within the urological domain, donor nephrectomy is multidisciplinary. Therefore, we compared the use of laparoscopy by procedure indication (kidney donor, and benign and malignant kidney disease) to examine potential specialty specific associations with the slow uptake of this technology. MATERIALS AND METHODS: Data on 53,461 patients undergoing nephrectomy for all indications between 1998 and 2003 were abstracted from the Nationwide Inpatient Sample using International Classification of Diseases, 9th Revision, Clinical Modification procedure and diagnostic codes. Generalized estimating equations were fitted to measure the association between laparoscopy use and the procedure indication (kidney donor, benign kidney disease and kidney cancer). RESULTS: The use of laparoscopy varied by treatment indication. In 2003, 33% of kidney donors underwent a laparoscopic approach compared to 22% and 16% of patients with benign and malignant kidney disease, respectively (p <0.0001). After adjusting for patient and hospital differences patients with benign (adjusted OR 0.71, 95% CI 0.58-0.94) and malignant (adjusted OR 0.51, 95% CI 0.35-0.74) kidney disease were significantly less likely to undergo laparoscopic nephrectomy than kidney donors. CONCLUSIONS: These data highlight that the use of laparoscopic renal surgery varies by procedure indication with slower adoption of laparoscopy for malignant or benign indications than for donor nephrectomy. This variation was not readily explained by differences in measurable patient and hospital factors. Further characterization of provider and nonclinical characteristics may provide additional insight into differences in the adoption of this technology, which appears to be a specialty specific phenomenon. PMID- 17870128 TI - Trends in regionalization of inpatient care for urological malignancies, 1988 to 2002. AB - PURPOSE: Higher hospital and clinician volumes may be associated with improved patient outcomes for complex surgical and medical care, although the strength and consistency of this association varies markedly across specific conditions and procedures. Pressures from payors and policymakers exist to move complex care to high volume hospitals. The net effect of these pressures may be the regionalization of care. We quantified trends in the regionalization of inpatient care for urological oncology in a national administrative database. MATERIALS AND METHODS: The Nationwide Inpatient Sample, a 20% stratified sample of United States community hospital admissions, was queried for surgical and nonsurgical admissions for bladder, renal and prostate cancer care between 1988 and 2002. Hospitals were grouped into tertiles by annual surgical volume. Trends over time in the annual discharge rate by hospital volume tertile, geographic region and insurance status were analyzed. RESULTS: High volume hospitals were defined by at least 22, 12 and 26 cases per year for bladder, renal and prostate cancer, respectively. High volume hospital discharges increased significantly as a proportion of all discharges for bladder (67% to 70%) and renal (67% to 73%) cancer surgery, and they were essentially constant for prostate surgery (76%). Trends were similar for Medicare and Medicaid patients except high volume hospital discharges for prostate cancer decreased during the study period. Significant regional variation was observed for the regionalization of surgical and nonsurgical care. CONCLUSIONS: Nationwide Inpatient Sample data demonstrate the ongoing regionalization of urological oncology care. The policy implications of this trend are complex with potentially important benefits and risks in terms of access to and quality of care. PMID- 17870132 TI - Mitochondrial DNA fragments released through the permeability transition pore correspond to specific gene size. AB - In the present work, we show that after induction of mitochondrial damage by oxidative stress, in the presence of calcium, matrix DNA content decreased to 42+/-6%. Mitochondrial damage was analyzed by measuring aconitase activity, a marker enzyme of mitochondrial oxidative stress. The genes were identified by amplifying them through the polymerase chain reaction (PCR), using specific primers for each mitochondrial gene (MTCO1, MTCO2, MTCO3, MTND3, MTND5, MTATP6, MTATP8, and MTCYB). The results show that after oxidative stress, the amount of MTCO1, MTND3, and MTCYB genes in the mitochondria approximately decreased by 46, 22, and 54%, respectively. This effect was inhibited in the presence of cyclosporin A. These genes were found outside the mitochondria after permeability transition was induced. Mitochondrial integrity was evaluated by observing the activity of adenylate kinase and malate dehydrogenase. PMID- 17870133 TI - Time course of neural and contractile disturbances in a rat model of colitis induced by Trichinella spiralis. AB - Colitis induced by Trichinella spiralis in rat induces alterations in the spontaneous motor pattern displayed by circular colonic muscle [Auli, M., Fernandez, E., 2005. Characterization of functional and morphological changes in a rat model of colitis induced by T. spiralis. Digestive Diseases and Sciences 50(8), 1432-1443]. We examined the temporal relationship between the severity of inflammation and the altered contractility of the underlying circular muscle as well as the role of NANC inhibitory pathways in the disruption of the motility pattern. Colitis was induced by intrarectal administration of T. spiralis larvae. Responses to acetylcholine (ACh) and increased extracellular potassium as well as the effect of tetrodotoxin (TTX, 1 microM), N-nitro-l-arginine (L-NOARG, 1 mM) and apamin (1 microM) were determined in vitro in the organ bath with circular muscle strips from sham-infected and infected rats at days 2-30 postinfection (PI). Microelectrode recordings were performed to study the putative changes in electrical activity of colonic smooth muscle cells. Responses to ACh and KCl were decreased at all days PI compared to sham. Intracellular calcium depletion had a greater inhibitory effect in inflamed tissue (6-14 PI). The effect of TTX, L NOARG and apamin on the spontaneous contractions was found to be altered in all infected rats, i.e. their effects were transient and milder. Inflamed tissue showed lower resting membrane potential and a decreased duration of inhibitory junction potentials induced by electrical stimulation. These data suggest that the decreased contractility of colonic circular smooth muscle induced by the intrarectal T. spiralis infection results from the impairment of the excitation contraction coupling, from a persistent hyperpolarization of smooth muscle cells and from impaired NANC inhibitory neurotransmission. PMID- 17870134 TI - Streptozotocin-induced diabetes increases the interaction of Bad/Bcl-XL and decreases the binding of pBad/14-3-3 in rat testis. AB - Sexual dysfunction is frequently associated with diabetes in males. The present study was designed to evaluate whether streptozotocin-induced diabetes increases apoptotic cell death in rat testis through the regulation of Bcl-2 family proteins. Diabetes was induced by a single intravenous injection of streptozotocin (40 mg/kg body weight) and testis samples were collected after 3 months. The number of positive cells for TUNEL histochemistry was significantly increased in the testicular germ cells of the diabetic group, compared to those of control. The levels of Bcl-2 and Bcl-X(L), anti-apoptotic proteins, were decreased in the diabetic group. In contrast, the levels of Bax and Bad, pro apoptotic factors, were increased in the diabetic group, compared with the control group. Moreover, the diabetic condition increased the interaction of Bad and Bcl-X(L), and decreased the binding of pBad and 14-3-3. 14-3-3 acts as an anti-apoptotic factor through interaction with Bad. Our findings suggest that streptozotocin-induced diabetes increases apoptotic cell death in testis tissue through the up-and down-regulation of Bcl-2 family proteins and the interaction of Bad and Bcl-X(L). PMID- 17870135 TI - Ultra-low dose cannabinoid antagonist AM251 enhances cannabinoid anticonvulsant effects in the pentylenetetrazole-induced seizure in mice. AB - Several lines of evidence suggest that cannabinoid compounds are anticonvulsant since they have inhibitory effects at micromolar doses, which are mediated by activated receptors coupling to Gi/o proteins. Surprisingly, both the analgesic and anticonvulsant effects of opioids are enhanced by ultra-low doses (nanomolar to picomolar) of the opioid antagonist naltrexone and as opioid and cannabinoid systems interact, it has been shown that ultra-low dose naltrexone also enhances cannabinoid-induced antinociception. However, regarding the seizure modulating properties of both classes of receptors this study investigated whether ultra-low dose cannabinoid antagonist AM251 influences cannabinoid anticonvulsant effects. The clonic seizure threshold (CST) was tested in separate groups of male NMRI mice following injection of vehicle, the cannabinoid selective agonist arachidonyl-2-chloroethylamide (ACEA) and ultra-low doses of the cannabinoid CB1 antagonist AM251 and a combination of ACEA and AM251 doses in a model of clonic seizure induced by pentylenetetrazole (PTZ). Systemic administration of ultra-low doses of AM251 (10 fg/kg-100 ng/kg) significantly potentiated the anticonvulsant effect of ACEA at 0.5 and 1 mg/kg. Moreover, inhibition of cannabinoid induced excitatory signaling by AM251 (100 pg/kg) unmasked a strong anticonvulsant effect for very low doses of ACEA (100 ng/kg-100 microg/kg), suggesting that a presumed inhibitory component of cannabinoid receptor signaling can exert strong seizure protective effects even at very low levels of cannabinoid receptor activation. A similar potentiation by AM251 (100 pg/kg and 1 ng/kg) of anticonvulsant effects of non-effective dose of ACEA (0.5 and 1 mg/kg) was also observed in the generalized tonic-clonic model of seizure. The present data suggest that ultra low doses of cannabinoid receptor antagonists may provide a potent strategy to modulate seizure susceptibility, especially in conjunction with very low doses of cannabinoids. PMID- 17870136 TI - Anxiolytic-like action of MTEP expressed in the conflict drinking Vogel test in rats is serotonin dependent. AB - The purpose of the present study was to investigate whether the anxiolytic-like action of a selective and brain penetrable group I metabotropic glutamate (mGlu5) receptor antagonist 3-[(2-methyl-1,3-tiazol-4-yl)ethynyl]-pyridine (MTEP) is dependent upon the serotonergic system. Experiments were performed on male Wistar rats. The Vogel conflict drinking test was used to detect anxiolytic-like activity. MTEP administered intraperitoneally at doses of 1, 3 and 6 mg/kg induced anxiolytic-like effect. The potential anxiolytic effect of MTEP (1 mg/kg) was inhibited by a nonselective 5-HT receptor antagonist metergoline (2 mg/kg i.p.) and 5-HT2A/2C receptor antagonist ritanserin (0.5 mg/kg i.p.), but not by a 5-HT1A receptor antagonist N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2 pyridynyl)cyclohexane-carboxamide (WAY 100635) (0.1 mg/kg i.p). The anxiolytic effect of MTEP (6 mg/kg) was attenuated by ritanserin (1 mg/kg i.p.). Moreover, MTEP-induced a dose-dependent release of serotonin in the frontal cortex. The obtained results suggest that the potential anxiolytic effect of the mGlu5 receptor antagonist MTEP is due to the increased serotonin release with subsequent activation of 5-HT2A/2C receptors, most probably located postsynaptically, but not by the 5-HT1A receptors. PMID- 17870137 TI - Dihydroisocoumarin from Xyris pterygoblephara active against dermatophyte fungi. AB - The ethanol extract from Xyris pteygoblephara aerial parts was evaluated against five microorganism strains, by the microdilution and agar diffusion methods. Extract fractionation led to the isolation of three compounds, whose structures were assigned by spectrometric data (1D and 2D NMR, IR, MS and UV) as (3R,4R)-(-) 6-methoxy-3,4-dihydro-3-n-pentil-4-acethoxy-1H-2-benzopyran-1-one (1), moronic acid and quercetin. The absolute configuration of 1 was defined by circular dichroism spectroscopy and comparison with data reported for other dihydroisocoumarins. Assay of 1 (100 microg/disc) by the agar diffusion method against clinical isolates of the dermatophytes Epidermophyton floccosum (inhibition zone, mm+/-s.d.: 4.5+/-0.8), Trichophyton mentagrophytes (4.8+/-0.4) and Trichophyton rubrum (10.2+/-0.8) revealed similar inhibition zones to the positive control amphotericin B (32 microg/disc; 5.0+/-0.2; 5.0+/-0.6 and 8.8+/ 1.2, respectively). The result corroborates the ethnomedical use of Xyris species to treat dermatitis. PMID- 17870138 TI - UDP-glucose:(6-methoxy)podophyllotoxin 7-O-glucosyltransferase from suspension cultures of Linum nodiflorum. AB - Cell cultures of Linum species store 6-methoxypodophyllotoxin (MPTOX), podophyllotoxin (PTOX) and related lignans as O-glucosides. UDP-glucose:(M)PTOX 7 O-glucosyltransferase has been detected and characterised in protein preparations of suspension-cultured cells of Linum nodiflorum L. (Linaceae). The maximal lignan glucoside contents in the cells are preceded by a rapid increase of the specific glucosyltransferase activity on day six of the culture period. MPTOX glucoside is the major lignan with up to 1.18 mg g(-1) of the cell dry wt which is more than 30-fold of the PTOX glucoside content. Of the three aryltetralin lignans tested as substrates, PTOX and MPTOX display comparable apparent K(m) values of 4.7 and 5.4 microM, respectively. 5'-Demethoxy-6-methoxypodophyllotoxin is converted with the highest velocity of 25.2 pkat mg(-1) while also possessing a higher K(m) of 14.7 microM. Two-substrate test series indicate that all three compounds compete for the active site of a single protein. The structurally similar lignan beta-peltatin acts as competitive inhibitor as well. However, the 6-O-glucosidation is most likely catalysed by a separate enzyme. The (M)PTOX 7-O glucosyltransferase works best at a pH around 9 and a temperature around 35 degrees C. A 15-30% increase of the reaction rate is effected by the addition of 0.9 mM Mn(2+). PMID- 17870139 TI - Aspects of the association between leishmaniasis and malignant disorders. AB - Given the prevalence of leishmaniasis and cancer, the co-existence of these two diseases may be merely coincidental. However, a number of epidemiological, experimental and laboratory studies suggest that an association between these two entities does exist. The aim of this review is to summarise the occurrence of leishmaniasis as an opportunistic infection associated with malignant disorders and to present the available literature potentially linking this infection with the development of cancerous lesions. We searched electronic databases and evaluated 37 studies involving 44 patients. Four different types of association between leishmaniasis and cancer were established: leishmaniasis mimicking a malignant disorder, such as lymphoma; leishmaniasis arising as a difficult to diagnose and treat infection among patients receiving chemotherapy for various malignant disorders; simultaneous diagnosis of leishmaniasis and a neoplastic disorder in the same tissue samples of immunocompromised patients; and direct involvement of Leishmania spp. in the pathogenesis/occurrence of malignant lesions, especially of the skin and mucous membranes. The main conclusion of this review is that leishmaniasis can directly or indirectly affect the presentation, diagnosis and course of various malignant disorders and it should be considered in the differential diagnosis of malignancies in geographic areas where it is endemic and/or in patients with travel history to these areas. PMID- 17870140 TI - Molecular cloning of albolatin, a novel snake venom metalloprotease from green pit viper (Trimeresurus albolabris), and expression of its disintegrin domain. AB - Disintegrins are snake venom-derived, RGD- or KGD-containing peptides that can inhibit integrin-mediated platelet aggregation and cell-matix interactions. The aim of this study is to analyze the full-length cDNA sequence of a snake venom metalloprotease (SVMP) from green pit viper (Trimeresurus albolabris) venom and characterize functions of its disintegrin domain on human platelets. From the primary cDNA library of venom glands, a partial sequence of a novel SVMP (Albolatin) was obtained. Using the 5'-RACE, the 2040bp full-length sequence of albolatin mRNA was derived. The deduced amino acid sequence revealed a type P-II SVMP of 484 amino acid residues comprising a signal region, pro-peptide, inactive metalloprotease domain and a disintegrin domain. It showed 85% amino acid identical to Trimeresurus jerdonii jerdonitin and 81% to Gloydius halys agkistin. Sequence alignment revealed that all cysteines were conserved except for an extra cysteine in the protease domain of albolatin. The disintegrin domain of albolatin, which comprised 76 amino acids with a KGDW sequence, was expressed in Pichia pastoris with the yield of 3.3mg/L of culture medium. The molecular weights were 11kDa in reduced and 22kDa in non-reduced states indicating a homodimer. It can inhibit collagen-induced platelet aggregation with IC(50) of 976nM and, therefore, should be investigated for a potential to be a novel therapeutic agent. PMID- 17870141 TI - Transspecies transmissions of retroviruses: new cases. AB - Transspecies transmission is common among retroviruses, although the consequences of the transmission are very different. Some transspecies transmissions have resulted in fatal diseases in the new host while others have remained asymptomatic. Some retroviruses are apathogenic in the original species, but pathogenic in a new host and others can be pathogenic or apathogenic in both species. In some cases, endogenization of the retrovirus in the new host has been observed but in others not, while some transmitted retroviruses exist in both forms. Although in most cases transspecies transmission has been observed in one direction only, bidirectional transmissions of caprine and ovine lentiviruses have recently been described. Studies on newly reported natural and experimental transspecies transmissions of the koala retrovirus (KoRV) may help to understand such events. PMID- 17870142 TI - Degradability of ethylenediaminedisuccinic acid (EDDS) in metal contaminated soils: implications for its use soil remediation. AB - Previous research has identified ethylenediaminedisuccinate (EDDS) as a promising biodegradable alternative for persistent compounds such as EDTA for application in soil washing or enhanced phytoextraction of heavy metals. This study examines heavy metal mobilization in three polluted soils varying in soil composition, with specific attention for competitive behaviour for complexation between the various metals and major elements, such as Al, Fe, Mn, Ca and Mg. In addition, amendment biodegradability was compared between the different soil types. The selected soils included a moderately contaminated calcareous clayey soil, a dredged sediment derived surface soil with similar soil characteristics yet more heavily polluted with Cd, Cr and Zn, and a sandy soil moderately contaminated by historical smelter activity (atmospheric deposition). Biodegradability of EDDS in the three soils varied distinctly. This was mainly expressed in the duration of the lag phase prior to metal complex degradation, and not so much in the half life when degradation effectively did set in. Differences in the lag phase were attributed to differences in soil pollution. However, EDDS was fully degraded within a period of 54 d in all soils regardless of initial delay. Assessment of the cation mobilisation patterns in the three soils under study revealed that mainly Ca, Fe and Al can reduce effectiveness of heavy metal mobilisation by competition for complexation. PMID- 17870143 TI - Effects of low dissolved oxygen on organisms used in freshwater sediment toxicity tests. AB - Minimum dissolved oxygen requirements are part of standard guidelines for toxicity testing of freshwater sediments with several benthic invertebrates, but the data underlying these requirements are somewhat sparse. We exposed three common test organisms to ranges of dissolved oxygen concentrations to determine their responses in 10-d exposures, relative to published guidelines for sediment toxicity tests. The oligochaete, Lumbriculus variegatus, showed 100% survival in all exposures down to the lowest concentration tested, 0.7 mg O(2)l(-1). Midge (Chironomus dilutus) larva showed a more pronounced response; while survival was less than 90% only below 1.0mg O(2)l(-1), the biomass endpoint showed EC(50), EC(20), and EC(10) values of 1.00 (0.91-1.10), 1.41 (1.16-1.71), and 1.67 (1.25 2.24) mg O(2)l(-1). The amphipod, Hyalella azteca, showed no adverse effects at concentrations as low as 2.12 mg O(2)l(-1). The combination of these data with other literature data suggest that DO minima in current North American 10-d sediment test guidelines are reasonable. PMID- 17870144 TI - Effect of mono-ortho and di-ortho substituted polychlorinated biphenyl (PCB) congeners on leopard frog survival and sexual development. AB - We tested the effect of mono-ortho and di-ortho PCB congeners on northern leopard frog (Rana pipiens) hatching success, survival and sexual development. Embryos and tadpoles were exposed to two levels (0.5 and 50 microg/l) of two PCBs. PCBs 101 and 70 were selected because they were present in amphibians collected in the Fox River-Green Bay ecosystem and they have the theoretical structural requirements to be able to bind to the estrogen receptor and mediate estrogenic responses. The exposure of leopard frog embryos and tadpoles to PCB 70 and 101 did not significantly affect hatchability, survival, deformities or growth. There were significant departures from the expected 50:50 sex ratio in tadpoles/froglets exposed to PCB 101 and PCB 70. In all the cases of significant departure, the bias was towards higher number of females. Decrease in the proportion of male gonads and increase in the proportion of intersex gonads were observed with increasing PCB tissue concentrations. The effects of PCB congeners on sexual differentiation occur at concentrations higher than observed in frogs in the Fox River/Green Bay ecosystem. PMID- 17870145 TI - Organic carbon effects on aerobic polychlorinated biphenyl removal and bacterial community composition in soils and sediments. AB - Certain organic compounds, including biphenyl and salicylic acid, stimulate polychlorinated biphenyl (PCB) degradation by microorganisms in some environments. However, the usefulness of these amendments for improving PCB removal by microorganisms from diverse habitats has not been extensively explored. This study evaluated the effects of biphenyl, salicylic acid, and glucose on changes in aerobic PCB removal and bacterial communities from an agricultural soil, a wetland peat soil, a river sediment, and a mixture of these samples. PCB removal patterns were significantly different between soils and sediments amended with carbon compounds: (i) terrestrial soil microorganisms removed more PCBs than river sediment microorganisms, particularly with regard to PCBs with >4 chlorine substituents, (ii) glucose-supplemented, agricultural soil microorganisms removed more hexachlorobiphenyl than unsupplemented samples, (iii) biphenyl-supplemented, river sediment microorganisms removed more di- and tri chlorobiphenyls than unamended samples. Carbon amendments also caused unique shifts in soil and sediment bacterial communities, as determined by specific changes in bacterial 16S rRNA denaturing gradient gel electrophoresis banding patterns. These results indicate that organic carbon amendments had site-specific effects on bacterial populations and PCB removal. Further work is needed to more accurately characterize PCB degrading communities and functional gene expression in diverse types of environments to better understand how they respond to bioremediation treatments. PMID- 17870146 TI - Establishing baseline levels of trace elements in blood and skin of bottlenose dolphins in Sarasota Bay, Florida: implications for non-invasive monitoring. AB - Several major unusual mortality events occurring in recent years have increased the level of concern for the health of bottlenose dolphin populations along the United States Atlantic and Gulf of Mexico coasts. Trace element concentrations were examined in a population of free-ranging dolphins in Sarasota Bay, Florida, in order to develop a benchmark for future comparisons within and between populations. Whole blood (n=51) and skin (n=40) samples were collected through capture and release health assessment events during 2002-2004. Samples were analyzed for Al, V, Cr, Mn, Cu, Zn, As, Se, Rb, Sr, Mo, Cd, and Pb by inductively coupled plasma mass spectrometry (ICPMS) and Hg via atomic fluorescence spectrometry (AFS). Trace element concentrations (wet mass) in skin were 2 to 45 times greater than blood, except Cu was approximately 1.5 times higher in blood. Statistically strong correlations (p<0.05) were found for V, As, Se, Rb, Sr, and Hg between blood and skin demonstrating that these tissues can be used as effective non-lethal monitoring tools. The strongest correlation was established for Hg (r=0.9689) and concentrations in both blood and skin were above the threshold at which detrimental effects are observed in other vertebrate species. Female dolphins had significantly greater Hg concentrations in blood and skin and Pb concentrations in skin, relative to males. Calves exhibited significantly lower V, As, and Hg concentrations in blood and V and Hg concentrations in skin, relative to other age classes. Rubidium and Cu concentrations in skin were greatest in subadults and calves, respectively. In blood, V, Zn, and As concentrations were significantly greater in winter, relative to summer, and the opposite trend was observed for Rb and Sr concentrations. In skin, Cu and Zn concentrations were significantly greater in winter, relative to summer, and the opposite trend was observed for Mn, Rb, Cd, and Pb concentrations. The baseline concentrations and trends established in this study will serve as a benchmark for comparison and aid in sampling design for future monitoring of this population and other coastal bottlenose dolphin populations. PMID- 17870147 TI - Hyperfibrinolysis in alcoholic cirrhosis: relative plasminogen activator inhibitor type 1 deficiency. AB - BACKGROUND: Over activity of the fibrinolytic system (hyperfibrinolysis) occurs in cirrhosis and has been shown to correlate with the risk of variceal hemorrhage. We have developed a model for assessing acute tissue plasminogen activator (t-PA) release in vivo in man. The aims of the study were to assess the contribution of basal and stimulated t-PA release to hyperfibrinolysis in patients with alcoholic cirrhosis. METHODS: Bilateral forearm blood flow and plasma fibrinolytic variables were measured in 8 patients with biopsy proven alcohol induced cirrhosis, ascites and portal hypertension, and 8 age and sex matched healthy controls during infusion of bradykinin (100-900 pmol/min; endothelium-dependent vasodilator that releases t-PA) followed by sodium nitroprusside (SNP 2-8 microg/min; a control endothelium-independent vasodilator). RESULTS: Baseline plasma t-PA antigen concentrations were higher in patients (14+/-2 vs 9+/-1 ng/mL; p<0.05) whereas plasma plasminogen activator inhibitor type-1 (PAI-1) antigen concentrations were similar (59+/-16 vs 55+/-11 ng/mL; p=NS). This resulted in an increased t-PA activity (3+/-1 vs 0+/-0 IU/mL; p<0.05) and reduced PAI-1 activity (9+/-2 vs 21+/-2 AU/mL; p<0.05) indicating a relative deficiency of PAI-1 in patients with cirrhosis. Bradykinin and SNP caused dose-dependent vasodilatation (p<0.001 for both) that did not differ between the two groups. Bradykinin caused a similar release of t-PA antigen (p<0.05 for both) in both patients and controls (24+/-17 vs 23+/-7 ng/100 mL/min; p=ns) without affecting PAI-1 concentrations. Local t-PA activity was increased in patients following acute stimulated t-PA release (5+/-1 vs 3+/-1 IU/mL; p<0.05). SNP caused no significant change in fibrinolytic parameters. CONCLUSION: Patients with alcoholic cirrhosis have a higher basal plasma t-PA activity because of a failure to increase plasma concentrations of its inhibitor, PAI-1. Furthermore, despite releasing normal amounts of t-PA acutely, higher t-PA activity remained due to the relative deficiency of PAI-1. This suggests that the pathogenesis of hyperfibrinolysis in alcoholic cirrhosis is the result of a relative PAI-1 deficiency and enhanced basal t-PA release. PMID- 17870148 TI - Platelet adhesion in congestive heart failure. PMID- 17870149 TI - Integrating metabolomics and phenomics with systems models of cardiac hypoxia. AB - Hypoxia is the major cause of necrotic cell death in myocardial infarction. Cellular energy supply and demand under hypoxic conditions is regulated by many interacting signaling and transcriptional networks, which complicates studies on individual proteins and pathways. We apply an integrated systems approach to understand the metabolic and functional response to hypoxia in muscle cells of the fruit fly Drosophila melanogaster. In addition to its utility as a hypoxia tolerant model organism, Drosophila also offers advantages due to its small size, fecundity, and short life cycle. These traits, along with a large library of single-gene mutations, motivated us to develop new, computer-automated technology for gathering in vivo measurements of heart function under hypoxia for a large number of mutant strains. Phenotype data can be integrated with in silico cellular networks, metabolomic data, and microarrays to form qualitative and quantitative network models for prediction and hypothesis generation. Here we present a framework for a systems approach to hypoxia in the cardiac myocyte, starting from nuclear magnetic resonance (NMR) metabolomics, a constraint-based metabolic model, and phenotypic profiles. PMID- 17870150 TI - Management of platinum-sensitive recurrent ovarian cancer: a cost-effectiveness analysis. AB - OBJECTIVE: We wished to compare the cost-effectiveness of three chemotherapy regimens for treatment of recurrent platinum-sensitive ovarian cancer. METHODS: A Markov decision tree was constructed comparing three chemotherapy regimens: (1) carboplatin alone (C); (2) paclitaxel/carboplatin (PC); (3) gemcitabine/carboplatin (GC). Progression-free survival (PFS) and adverse event rates were estimated from published randomized controlled trials (RCTs). Costs of treatment and adverse events were obtained using Medicare reimbursement data. RESULTS: Estimated mean and median progression-free survival were 8.0 and 6.0 months for C, 10.1 and 7.8 months for PC, 10.5 and 8.4 months for GC, respectively. C was the least expensive strategy, costing $501 per progression free month (PFM). PC had an incremental cost-effectiveness ratio (ICER) of $1297 per additional PFM ($15,564 per additional progression-free year (PFY)) compared to C. GC had an ICER of $23,199 per additional PFM ($278,388 per additional PFY) compared to PC. Results were insensitive to variation in the rates and costs of toxicities over clinically reasonable ranges. The model was sensitive to changes in PFS estimates. When the PFS of GC was assumed to be equivalent to that of PC, GC was strongly dominated (more expensive and no more effective) by PC due to the additional costs. Adjustment for neurotoxicity-associated quality of life (QoL) did not change rankings of strategies. CONCLUSIONS: PC appears to be relatively cost-effective compared to C for the treatment of recurrent platinum-sensitive ovarian cancer. GC appears to be less cost-effective compared to PC, with an ICER ten times higher. PMID- 17870151 TI - A theory-aided dissemination strategy for emerging technologies in cervical cancer screening. PMID- 17870152 TI - New frontiers in kisspeptin/GPR54 physiology as fundamental gatekeepers of reproductive function. AB - Identification, in late 2003, of inactivating mutations of the G protein-coupled receptor GPR54 as causative factor for absence of puberty and hypogonadotropic hypogonadism in humans and mice was a major breakthrough in modern Neuroendocrinology, and drew considerable interest on the characterization of the roles of this receptor and its ligands (kisspeptins, encoded by the KiSS-1 gene) in the physiological control of essential facets of reproduction. After 3 years of intense research activity, kisspeptins are universally recognized as essential activators of the gonadotropic axis, with key roles in puberty onset and the control of gonadotropin secretion. While these fundamental functions are now well settled, novel aspects of kisspeptin/GPR54 physiology have emerged, including their involvement in the neuroendocrine control of ovulation and the metabolic gating of reproductive function. In addition, the 'comparative endocrinology' of this system has begun to be explored recently. These facets of kisspeptin/GPR54 function, as fundamental gatekeepers of reproduction, will be comprehensively reviewed herein. PMID- 17870153 TI - Diagnosis of bovine freemartinism by fluorescence in situ hybridization on interphase nuclei using a bovine Y chromosome-specific DNA probe. AB - A heifer co-twin to a bull, in most cases, is a sterile freemartin which needs to be identified and culled from replacement stock. Various methods are available for the diagnosis of freemartinism, but none is ideal in terms of speed, sensitivity, or specificity. The present study was thus conducted to develop and validate a satisfactory fluorescence in situ hybridization procedure on interphase nuclei (I-FISH) for identifying the bovine XX/XY-karyotypic chimerism, the hallmark of freemartinism. A 190-bp DNA FISH probe containing the bovine male specific BC1.2 DNA sequence was synthesized and labeled with digoxigenin by PCR. The FISH was performed on metaphase spreads and interphase nuclei of blood lymphocytes. Upon FISH, the probe expectedly bound to the nucleus of the male cell or to a region of the p12 locus of the Y chromosome. Twenty-four young heterosexual twins (Holstein-Friesian and Korean Cattle breeds; 10 pairs and 4 singletons) were analyzed in the present study; all but three exhibited the XX/XY karyotypic chimerism to varying extents in both I-FISH and karyotyping. One heifer was identified to have 100% XX cells by both analyses, whereas two bulls were judged as 100% XY- and XX/XY-chimeric karyotypes by karyotyping and I-FISH, respectively. Nevertheless, the ratios of the XY to XX cells in these animals were very similar between the two analyses. In conclusion, the present I-FISH was a rapid and reliable procedure that can be used for early-life diagnosis of bovine freemartinism. PMID- 17870154 TI - The 12-month prevalence of DSM-IV anxiety disorders among Nigerian secondary school adolescents aged 13-18 years. AB - AIMS: To estimate the 12-month prevalence of DSM-IV-specific anxiety disorders among Nigerian secondary school adolescents aged 13-18 years. METHOD: A representative sample of adolescents (n=1090) from senior secondary schools in a semi-urban town in Nigeria was assessed for the 12-month prevalence of DSM-IV specific anxiety. RESULTS: The 12-month prevalence for all anxiety disorders was 15.0% (females=19.6%; males=11.4%). There were significant gender differences in the prevalence for all anxiety disorders (P<0.001; OR 1.96, 95% CI 1.35-2.65) and social anxiety disorder (P=0.035; OR 1.82, 95% CI 1.03-3.19) and significant age difference in the prevalence of separation anxiety disorder (P=0.045; OR 2.43, 95% CI 0.99-5.96). CONCLUSION: The prevalence of anxiety disorders in Nigerian secondary school adolescents was comparable to the rates found in the western world. Health policies must integrate adolescents' anxiety as a disorder of public health significance. Further studies are needed to evaluate the factors associated with anxiety disorders amongst adolescents in this region. PMID- 17870155 TI - Evaluation of the applicability of a fuzzy index of ecosystem integrity (FINE) to characterize the status of Tyrrhenian lagoons. AB - The new index FINE, a multimetric, fuzzy-based index for the evaluation of environmental quality for Mediterranean transitional waters, was calculated using biotic data gathered between 2000 and 2006 at 15 stations in 4 Tyrrhenian transitional water ecosystems (Orbetello Lagoon, Padrongiano Delta, Stagno di S. Teodoro, and Stagno di Tortoli), i.e. in a different biogeographic sub-province respect to the one in which the index was developed and validated. The rationale of FINE is that certain attributes, selected on the basis of established principles of benthic ecology, are fundamental for lagoon ecosystem function. A set of other indices (Simpson's 1-lambda', the W-statistics, AMBI, and BOPA) was also calculated and compared to FINE outputs. FINE, 1-lambda', and the W statistics were significantly correlated with sedimentary organic matter content. Some stations were unequivocally assigned to the same ecological status, independently from the index used; for others, some discrepancies were evident. Mediterranean transitional waters probably share ecosystem complexities which are not yet fully captured by indices developed and validated elsewhere. PMID- 17870156 TI - The tooth attachment mechanism defined by structure, chemical composition and mechanical properties of collagen fibers in the periodontium. AB - In this study, a comparison between structure, chemical composition and mechanical properties of collagen fibers at three regions within a human periodontium, has enabled us to define a novel tooth attachment mechanism. The three regions include, (1) the enthesis region: insertion site of periodontal ligament (PDL) fibers (collagen fibers) into cementum at the root surface, (2) bulk cementum, and (3) the cementum-dentin junction (CDJ). Structurally, continuity in collagen fibers was observed from the enthesis, through bulk cementum and CDJ. At the CDJ the collagen fibers split into individual collagen fibrils and intermingled with the extracellular matrix of mantle dentin. Under wet conditions, the collagen fibers at the three regions exhibited significant swelling suggesting a composition rich in polyanionic molecules such as glycosaminoglycans. Additionally, site-specific indentation illustrated a comparable elastic modulus between collagen fibers at the enthesis (1-3 GPa) and the CDJ (2-4 GPa). However, the elastic modulus of collagen fibers within bulk cementum was higher (4-7 GPa) suggesting presence of extrafibrillar mineral. It is known that the tooth forms a fibrous joint with the alveolar bone, which is termed a gomphosis. Although narrower in width than the PDL space, the hygroscopic CDJ can also be termed as a gomphosis; a fibrous joint between cementum and root dentin capable of accommodating functional loads similar to that between cementum and alveolar bone. From an engineering perspective, it is proposed that a tooth contains two fibrous joints that accommodate the masticatory cyclic loads. These joints are defined by the attachment of dissimilar materials via graded stiffness interfaces, such as: (1) alveolar bone attached to cementum with the PDL; and (2) cementum to root dentin with the CDJ. Thus, through variations in concentrations of basic constituents, distinct regions with characteristic structures and graded properties allow for attachment and the load bearing characteristics of a tooth. PMID- 17870157 TI - Treatment-related acute myeloid leukemia with 11q23 translocation following treatment with fludarabine, cyclophosphamide and rituximab. PMID- 17870158 TI - Thrombosis of the corpora cavernosa complicating lenalidomide therapy of myelofibrosis. AB - Venous thrombosis is a well-recognized complication of lenalidomide therapy in patients with multiple myeloma, but its occurrence during the treatment of other hematologic malignancies is less well described. In this report, we detail the occurrence of corpora cavernosa thrombosis in a patient receiving lenalidomide for the therapy of myelofibrosis. This case highlights the need for clinical vigilance in patients who present with unusual symptoms during investigational therapy, and indicates that the occurrence of venous thrombosis complicating therapy with lenalidomide or related compounds is not isolated to patients with multiple myeloma. PMID- 17870159 TI - Inflicted skeletal trauma: the relationship of perpetrators to their victims. AB - OBJECTIVE: Although inflicted skeletal trauma is a very common presentation of child abuse, little is known about the perpetrators of inflicted skeletal injuries. Studies exist describing perpetrators of inflicted traumatic brain injury, but no study has examined characteristics of perpetrators of inflicted skeletal trauma. METHODS: All cases of suspected child physical abuse evaluated by the child abuse evaluation teams at Vanderbilt University Medical Center (January 1996 to August 2000) and at the Children's Hospital at Denver (January 1996 to December 1999) were reviewed for the presence of fractures. All children with inflicted fractures were entered into the study, and demographic data, investigative data, and identity of perpetrators were collected. RESULTS: There were a total of 630 fractures for 194 patients. The median number of fractures per patient was 2, and the maximum was 31. Sixty-three percent of children presented with at least one additional abusive injury other than the fracture(s). Perpetrators were identified in 79% of the cases. Nearly 68% of the perpetrators were male; 45% were the biological fathers. The median age of the children abused by males (4.5 months) significantly differed from the median age of those abused by females (10 months) (p=.003). CONCLUSION: In the cases where a perpetrator of inflicted fractures could be identified, the majority were men, most commonly the biological fathers. Children injured by men were younger than those injured by women. PMID- 17870160 TI - Coaching children about sexual abuse: a pilot study of professionals' perceptions. PMID- 17870161 TI - A randomized controlled trial of consensus-based child abuse case management. AB - OBJECTIVE: This study evaluates the effects of expert-assisted child abuse and neglect case management in the German child welfare and healthcare system as perceived by the case workers themselves. METHODS: Case workers with different professions (social workers, counselors, clinic-based and office-based psychotherapists, and physicians) participated in the study. They were responsible for 80 child protection cases which were enrolled for the study and randomly assigned either to expert-assisted case management or to case management as usual. The sample represented a broad range of child protection problems with alleged or confirmed physical abuse, sexual abuse, emotional abuse and/or neglect. The victims were between 0 and 18 years of age. The intervention group received two to six case review sessions provided by child protection experts from outside of the case workers' own institution within 6 months after referral of the case. The case workers' satisfaction with the perceived degree of child protection, their level of certainty in the process of investigation, risk assessment and intervention planning, the quality of inter-institutional communication, and the involvement of children and families were evaluated. RESULTS: Overall, only few between-group differences indicated effects of the intervention program. There was a statistical tendency toward more satisfaction with the perceived degree of child protection in the intervention group. Certainty in the estimation of suspected child abuse decreased significantly in the intervention group, compared with the control group, whereas certainty with respect to intervention planning increased. There were no group differences in the estimation of inter-institutional communication. Case workers in the intervention reported significantly fewer legal prosecutions of the perpetrators than case workers without expert assistance. However, the involvement of children in planning the interventions was significantly lower in the intervention group. CONCLUSIONS: Expert-assisted case management may change the case workers' perception of the evidence for abuse and guide their interventions to provide child protection. Modifications of the method should consider improved participation of the child. PMID- 17870162 TI - Activation of the TLR3 pathway regulates IFNbeta production in chickens. AB - Toll-like receptors (TLRs) play key roles in the response to pathogens and in mammals the host response to virus critically relies on TLR3 to detect viral derived dsRNA. However, in chickens there is a paucity of information about this pathway, and in view of the recent concerns with regard to highly pathogenic avian influenza, there is a clear need for understanding these antiviral pathways. Furthermore, TLR3 engagement is important to the outcome of viral infection because of its role in the induction of interferons (IFNs) and the diverse antiviral effects that these molecules induce. With this in mind, we have investigated the role of TLR3 and its impact on the production of IFNs. We show that in the chicken, poly(I:C), a dsRNA analogue, rapidly induces type 1 IFN similar to that seen in mammals. Furthermore, IFN can activate the upregulation of TLR3, which in some cell types induces them to become responsive to dsRNA. These data highlight the similar function that TLR3 plays in chickens and mammals. To determine the role of chicken TLR3 in response to poly(I:C), we used RNAi-mediated gene silencing to show that poly(I:C)-stimulated IFNbeta expression involves TLR3 signalling. The interrelationship between TLR3 and interferon as well as the observed increase in TLR3 and IFNbeta expression during H5N1 avian influenza infection indicates the importance of these molecules in viral infections in chickens. PMID- 17870163 TI - Geographic, seasonal and ontogenetic variation in cadmium and mercury concentrations in squid (Cephalopoda: Teuthoidea) from UK waters. AB - Cadmium (Cd) and mercury (Hg) levels were measured in the tissue samples of two loliginid (Alloteuthis sp. and Loligo forbesi) and two ommastrephid (Todarodes sagittatus and Todaropsis eblanae) squid species collected from research cruise and fishery (market) samples in UK waters during 2004-05. Concentrations of Cd were generally higher in the ommastrephids, in all tissues except muscle. Hg concentrations were higher in T. sagittatus than in the loliginids. In L. forbesi, metal concentrations differed between tissues and also varied in relation to body size, geographic origin, and season. Cd levels decreased with increasing body size. This may be related to a shift in the diet with growth, since small L. forbesi feed on benthic invertebrates that have relatively high Cd concentrations, whereas larger individuals prey mainly on fish that have low Cd concentrations. Hg levels increased with body size, indicating its retention, and they were highest at the end of the spawning season and in squid from the English Channel and the Scottish West Coast. It is likely that the ambient concentration of Hg in seawater plays an important part in its accumulation in squid tissues. As it is a short-lived species, L. forbesi may therefore function as a bioindicator species for Hg contamination of the marine environment. Our results indicate that there is no significant danger to humans from consuming squid from UK waters. PMID- 17870165 TI - Electrical stimulation of nervous system tissue. Introduction. PMID- 17870164 TI - Puerto Rican injection drug users: Prevention implications in Massachusetts and Puerto Rico. AB - This study examines whether place of residence is a factor associated with reporting a positive HIV/AIDS, Hepatitis C (HCV), or Sexually Transmitted Disease (STD) status in a sample of 400 injection drug users (IDUs) residing on the Island of Puerto Rico (N=139) and in western Massachusetts (N=261). Logistic regression models revealed that IDUs residing in western Massachusetts were 66% less likely to be HIV positive compared to IDUs residing in Puerto Rico (p<.000) while IDUs residing in western Massachusetts were about 67% less likely to have a positive STD status than those residing in Puerto Rico (p<.000). Place of residence was not significantly associated with HCV status. Results indicate the need to develop prevention programs tailored to the unique socio-cultural context of Puerto Rican IDUs residing on the Island of Puerto Rico whose circumstances differ from those in the mainland US. To reduce drug use, HIV/AIDS, HCV, and STDs among Puerto Ricans in both locales, the Capacity Enhancement Model is proposed in order to develop more effective prevention programs. PMID- 17870166 TI - The classical complement pathway plays a critical role in the opsonisation of uropathogenic Escherichia coli. AB - Urinary tract infection due to uropathogenic Escherichia coli is a common clinical problem. The innate immune system and the uroepithelium are critical in defence against infection. The complement system is both part of the innate immune system and influences the interaction between epithelium and pathogen. We have therefore investigated the mechanism by which uropathogenic E. coli activate complement and the potential for this to occur during clinical infection. The classical pathway is responsible for bacterial opsonisation when complement proteins are present at low concentrations. At higher concentrations the alternative pathway predominates but still requires the classical pathway for its initiation. In contrast the mannose binding lectin pathway is not involved. Early classical pathway components are present in the urine during infection and actively contribute to bacterial opsonisation. The classical pathway could be initiated by anti-E. coli antibodies of IgG or IgM subclasses that are present in urine during infection. Additionally immunoglobulin-independent mechanisms, such as direct C1q binding to bacteria, may be involved. In conclusion, uropathogenic E. coli are readily opsonised by complement in a classical pathway dependent manner. This can occur within the urinary tract during the development of clinical infection. PMID- 17870167 TI - Pigment epithelium-derived factor induces THP-1 macrophage apoptosis and necrosis by the induction of the peroxisome proliferator-activated receptor gamma. AB - Pigment epithelial-derived factor (PEDF) is a potent anti-angiogenic factor, partially through the induction of endothelial cell apoptosis. Here we report that PEDF can also induce the apoptosis of human THP-1 monocytic leukemia cell line-derived macrophage cells (THP-1 macrophages) and peroxisome proliferator activated receptor gamma (PPARgamma), a pleiotropic transcriptional factor is involved in the signaling. TUNEL and propidium iodide permeability assays demonstrated that PEDF dose- and time-dependently induces both apoptosis and necrosis of THP-1 macrophages while inducing the cleavages of procaspase-9, -3, the release of cytochrome c and the overexpression of p53. All these PEDF effects can be attenuated by either PPARgamma inhibitor GW9662 or PPARgamma small interfering RNA. The effects of PEDF can be reproduced by transient expression of PPARgamma by a PPARgamma-expression plasmid transfection. PEDF increased the expression and transcriptional activity of PPARgamma in THP-1 macrophages. In addition, PEDF also induced apoptosis in primary human monocyte-derived macrophages (MDMs) while inducing the expression of PPARgamma. Our observations indicate that PEDF induces macrophage apoptosis and necrosis through the signaling of PPARgamma. This suggests a novel mechanism through which PEDF can modulate inflammation. PMID- 17870168 TI - Identification of the HLA-DM/HLA-DR interface. AB - Human leukocyte antigen (HLA)-DM is a critical participant in antigen presentation that catalyzes the dissociation of the Class II-associated Invariant chain-derived Peptide (CLIP) from the major histocompatibility complex (MHC) Class II molecules. There is competition amongst peptides for access to an MHC Class II groove and it has been hypothesised that DM functions as a 'peptide editor' that catalyzes the replacement of one peptide for another within the groove. It is established that the DM catalyst interacts directly with the MHC Class II but the precise location of the interface is unknown. Here, we combine previously described mutational data with molecular docking and energy minimisation simulations to identify a putative interaction site of >4000A2 which agrees with known point mutational data for both the DR and DM molecule. The docked structure is validated by comparison with experimental data and previously determined properties of protein-protein interfaces. A possible dissociation mechanism is suggested by the presence of an acidic cluster near the N terminus of the bound peptide. PMID- 17870169 TI - Function of E-protein dimers expressed in catfish lymphocytes. AB - E-proteins are essential class I bHLH transcription factors that play a role in lymphocyte development. In catfish lymphocytes the predominant E-proteins expressed are CFEB (a homologue of HEB) and E2A1, which both strongly drive transcription. In this study the role of homodimerization versus heterodimerization in the function of these catfish E-proteins was addressed through the use of expression constructs encoding forced dimers. Constructs expressing homo- and heterodimers were transfected into catfish B cells and shown to drive transcription from the catfish IGH enhancer. Expression from an artificial promoter containing a trimer of muE5 motifs clearly demonstrated that the homodimer of E2A1 drove transcription more strongly (by a factor of 10-25) than the CFEB homodimer in catfish B and T cells, while the heterodimer showed intermediate levels of transcriptional activation. Both CFEB1 and E2A1 proteins dimerized in vitro, and the heterodimer CFEB1-E2A1 was shown to bind the canonical muE5 motif. PMID- 17870171 TI - Discriminating between normal and glaucoma-damaged eyes with the Heidelberg Retina Tomograph 3. AB - PURPOSE: To determine and validate the diagnostic ability of a linear discriminant function (LDF) based on global stereometric parameters obtained using the Heidelberg Retina Tomograph version 3 (HRT3) for discriminating between healthy eyes and eyes with glaucomatous visual field loss. DESIGN: Cross sectional study. PARTICIPANTS: The authors prospectively selected 81 consecutive healthy subjects and 85 consecutive patients with open-angle glaucoma. Another prospective sample of 225 normal eyes and 210 glaucoma eyes was used to evaluate how well the LDF performed in another population. METHODS: Participants were divided into 2 groups depending on the results of standard automated perimetry and intraocular pressure. All participants underwent imaging of the optic nerve head with the HRT3. MAIN OUTCOME MEASURES: The LDF was calculated according to the stepwise logistic regression results of global optic nerve head parameters and glaucoma probability score numerical values. The diagnostic accuracy of the LDF and other parameters included in the software of the HRT3 was evaluated in another independent population. RESULTS: Based on the results of the stepwise binary logistic regression analysis, the function proposed was LDF = 8.23 - 8.00 x contour line modulation temporal superior + 9.41 x cup shape measure - 4.07 x rim area. The areas under the receiver operating characteristic curve were 0.875 for the LDF, 0.845 for the Frederick S. Mikelberg (FSM) discriminant function, and 0.838 for the Reinhard O. W. Burk (RB) discriminant function. There were no significant differences between these values. The LDF and the FSM and RB discriminant functions yielded sensitivities of 74.2%, 70.4%, and 67.6%, respectively, at a fixed specificity of 85%. CONCLUSIONS: Compared with the HRT provided parameters, the proposed LDF exhibited higher diagnostic ability than most available analyses. The LDF had a better sensitivity and specificity balance than the FSM and RB discriminant functions, regardless of optic disc size. PMID- 17870170 TI - Retinal nerve fiber structure versus visual field function in patients with ischemic optic neuropathy. A test of a linear model. AB - PURPOSE: To test a linear model relating the regional loss in retinal nerve fiber (RNFL) thickness to the corresponding regional loss in sensitivity with data from patients with previous anterior ischemic optic neuropathy (AION). DESIGN: Case control study. PARTICIPANTS: Twenty-four individuals with AION and 20 with normal vision were tested. The time since the AION attack ranged from 5.2 months to more than 20.3 years (median, 2.95 years). METHODS: Eyes were tested with standard automated perimetry (SAP) and with optical coherence tomography (OCT), both RNFL thickness scans. The average RNFL thickness of the inferior and superior disc sectors was plotted against the average total deviations (linear units) of the corresponding superior and inferior arcuate field regions, and a linear model was fitted. According to the model, the RNFL thickness R=s(o)T+b, (1), where T is the relative SAP sensitivity loss (on a linear scale; e.g., for -3 dB, T = 0.5), s(o) is the RNFL thickness attributable to axons in the healthy or normal state (T = 1.0), and b is the residual RNFL measured when all sensitivity and axons are lost. MAIN OUTCOME MEASURES: Optical coherence tomography RNFL thickness and SAP sensitivity. RESULTS: The data from the AION patients resembled the data from glaucoma patients previously tested and were described by the linear model. For patients with SAP losses of more than -10 dB in the arcuate region, the RNFL thickness provided an estimate of residual RNFL thickness, b. The median value of b (45.5 microm) was similar to the value for patients with glaucoma. It varied among individuals (range, 30.4-63.3 microm), showing a very weak correlation with patient's age (r = 0.30) and the time since the AION episode (r = 0.26), but an excellent correlation (r(2) = 0.94; P<0.01) with the value of s(o), estimated from the unaffected eyes. CONCLUSIONS: The relationship between a structure (OCT RNFL thickness) and function (SAP sensitivity loss) is the same for patients with AION and glaucoma and can be approximated by a simple linear model. The model may provide a framework for identifying those patients with ganglion cell axons that are malfunctioning but are alive. PMID- 17870172 TI - Athymic nude mice are insensitive to low-level toluene-induced up-regulation of memory-related gene expressions in the hippocampus. AB - The function of the N-methyl-d-aspartate (NMDA) subtype of glutamatergic receptors is known to be antagonized by toluene, a well-characterized neurotoxic chemical known to impair memory functions. Recently, peripheral T cells have been clearly shown to play an important role in cognitive and behavioral functions. In the present study, we investigated the role of peripheral T cells in the hippocampal mRNA expression of memory-related genes induced by low levels of toluene exposure in mice. BALB/c wild-type (WT) and nude mice were exposed to 9ppm of toluene or filtered air (0ppm toluene; control groups) in a nose-only exposure chamber for 30min on 3 consecutive days followed by weekly sessions for 4 weeks. Twenty-four hours after the last exposure, the hippocampi were collected and the inducibility of memory-related genes was examined using a real-time quantitative PCR method. NMDA NR2A, calcium/calmodulin-dependent protein kinase IV (CaMKIV), cyclic AMP-responsive element binding protein 1 (CREB1), and BDNF were significantly up-regulated in the hippocampi of WT mice exposed to 9ppm of toluene, compared to the expressions observed in WT mice exposed to filtered air, but similar results were not observed in nude mice. To investigate the possible involvement of peripheral T cells in the toluene-induced up-regulation of memory related genes in WT mice, we examined the mRNA expression of Thy-1 (a pan T cell specific marker) and quantified the number of cells that were immunoreactive to a T cell antigen receptor, CD3 (CD3-ir). Both the expression of Thy-1 mRNA and the number of CD3-ir cells were significantly higher in the hippocampi of the WT mice exposed to 9ppm of toluene, compared with that in WT mice exposed to filtered air; similar results were not observed in nude mice. We also examined the expression of chemokine genes like CCL2 and CCL3. The expression of CCL3 mRNA was significantly up-regulated only in the toluene-exposed WT mice. Although other differences unrelated to immune function may exist between WT and nude mice from the same background, the findings of the present study strongly suggest that the recruitment of peripheral T cells in the hippocampi of BALB/c WT mice exposed to low levels of toluene may be involved in the toluene-induced up-regulation of memory-related genes at the mRNA level. PMID- 17870173 TI - Synthesis, structure and cytotoxicity of triphenylphosphinegold(I) sulfanylpropenoates. AB - The reaction of triphenylphosphinegold(I) chloride in ethanol in a 1:1 molar ratio with the 3-(aryl)-2-sulfanylpropenoic acids H(2)xspa [x: p=3-phenyl-, Clp=3 (2-chlorophenyl)-, -o-mp=3-(2-methoxyphenyl)-, -p-mp=3-(4-methoxyphenyl)-, -o hp=3-(2-hydroxyphenyl)-, -p-hp=3-(4-hydroxyphenyl)-, diBr-o-hp=3-(3,5-dibromo-2 hydroxyphenyl)-, f=3-(2-furyl)-, t=3-(2-thienyl)-, -o-py=3-(2-pyridyl)-; spa=2 sulfanylpropenoato] gave compounds of the type [Au(PPh(3))(Hxspa)], which were isolated and characterized as solids by elemental analysis, IR spectroscopy and FAB mass spectrometry and in solution by (1)H, (13)C and (31)P NMR spectroscopy. The structures of the complexes [Au(PPh(3))(HClpspa)], [Au(PPh(3))(H-o-mpspa)] and [Au(PPh(3))(H-p-mpspa)].2/3C(3)H(6)O were determined by X-ray diffractometry. Hydrogen bonding was found along with Au-S and Au-P bonds in all cases and weak pi-pi stacking was found in the H-p-mpspa derivative. The in vitro antitumour activities against the HeLa-229, A2780 and A2780cis cell lines were determined for all complexes. PMID- 17870174 TI - Unusual dimeric Zn(II)-cytosine complexes: new models of the interaction of Zn(II) with DNA and RNA. AB - Synthesis and crystal structure of two Zn(II) dimer complexes with 1 methylcytosine (1-MeC) are reported. In complex [Zn(2)Cl(4)(mu-1-MeC-O2,N3)(2)] (1), two 1-MeC ligands are bridging two ZnCl(2) moieties. In [Zn(2)(1-MeC N3)(4)(mu-SO(4))(2)].2H(2)O (2), the sulfates act as bridging ligands and 1-MeC are linked via N3 to Zn(II) as terminal ligands. Both complexes represent the first examples of Zn(II)-pyrimidine dimers. The potential biological significance of 1 and 2 is discussed. PMID- 17870175 TI - Synthesis, characterization and antifungal activity of a series of manganese(II) and copper(II) complexes with ligands derived from reduced N,N'-O phenylenebis(salicylideneimine). AB - A series of manganese(II) and copper(II) complexes with reduced Schiff bases derived from o-phenylenediamine has been prepared and characterized by elemental analysis, TG measurements, ESR, magnetic measurements, FTIR, UV-Visible spectra and conductivity. These complexes were found to be [MnL(H2O)n] and [CuL](H2O)n species with n=0-2. Their antifungal activity was evaluated on different human fungi including yeasts of the Candida genus (C. albicans, C. glabrata, C. tropicalis and C. parapsilopsis) some opportunistic moulds belonging to the Aspergillus (A. fumigatus, A. terreus and A. flavus), Scedosporium genus (S. apiospermum and S. prolificans) and some dermatophytes (M. gypseum, M. persicolor, T. mentagrophytes, M. canis and T. tonsurans). The manganese complexes showed a significant growth inhibition of the dermatophytes tested and fungi of the genus Scedosporium. This is very interesting as these fungi are usually poorly susceptible to current antifungal including Amphotericin B and Itraconazole chosen as reference in this study. PMID- 17870176 TI - Complex mental activity and the aging brain: molecular, cellular and cortical network mechanisms. AB - There is strong evidence to suggest that high levels of complex mental activity can improve clinical outcome from brain injury. What are the neurobiological mechanisms underlying this observation? This paper proposes that complex mental activity induces a spectrum of biological changes on brain structure and function which can be best understood in a multiscalar spatiotemporal framework. Short term molecular changes may include induction of BDNF, NGF and endopeptidase genes and elevation of the high-energy phosphocreatine-creatine resting state equilibrium. Animal models have implicated these processes in the reduction and even reversal of neurodegenerative changes secondary to mental work. These mechanisms can therefore be described as neuroprotective. Medium-term cellular changes are diverse and include neurogenesis, synaptogenesis, angiogenesis and formation of more complex dendritic branching patterns. Importantly, these effects parallel behavioral improvement, and thus a neurogenerative class of mechanisms is implicated. Finally, in the post-lesion context, computation principles such as efficiency, small world connectivity and functional adaptation are identified as important, with supportive clinical evidence from neuroimaging studies. Thus, dynamic compensatory cortical network mechanisms may also be relevant, yet take some time to evolve. This paper will explore the neurobiological and clinical implications of this framework, in particular in the context of age-related brain disease. PMID- 17870177 TI - Laboratory production of 100 base pair DNA molecular weight markers. AB - DNA molecular weight markers are routinely used in agarose gel electrophoresis. Here we report a method called PCR-synthesized marker (PSM) to generate DNA molecular rulers by PCR in the laboratory. This strategy can also be used to produce 100 bp RNA molecular weight markers by run-off transcription. PMID- 17870178 TI - Detergent-resistant membrane subfractions containing proteins of plasma membrane, mitochondrial, and internal membrane origins. AB - HEK293 cell detergent-resistant membranes (DRMs) isolated by the standard homogenization protocol employing a Teflon pestle homogenizer yielded a prominent opaque band at approximately 16% sucrose upon density gradient ultracentrifugation. In contrast, cell disruption using a ground glass tissue homogenizer generated three distinct DRM populations migrating at approximately 10%, 14%, and 20% sucrose, named DRM subfractions A, B, and C, respectively. Separation of the DRM subfractions by mechanical disruption suggested that they are physically associated within the cellular environment, but can be dissociated by shear forces generated during vigorous homogenization. All three DRM subfractions possessed cholesterol and ganglioside GM1, but differed in protein composition. Subfraction A was enriched in flotillin-1 and contained little caveolin-1. In contrast, subfractions B and C were enriched in caveolin-1. Subfraction C contained several mitochondrial membrane proteins, including mitofilin and porins. Only subfraction B appeared to contain significant amounts of plasma membrane-associated proteins, as revealed by cell surface labeling studies. A similar distribution of DRM subfractions, as assessed by separation of flotillin-1 and caveolin-1 immunoreactivities, was observed in CHO cells, in 3T3 L1 adipocytes, and in HEK293 cells lysed in detergent-free carbonate. Teflon pestle homogenization of HEK293 cells in the presence of the actin-disrupting agent latrunculin B generated DRM subfractions A-C. The microtubule-disrupting agent vinblastine did not facilitate DRM subfraction separation, and DRMs prepared from fibroblasts of vimentin-null mice were present as a single major band on sucrose gradients, unless pre-treated with latrunculin B. These results suggest that the DRM subfractions are interconnected by the actin cytoskeleton, and not by microtubes or vimentin intermediate filaments. The subfractions described may prove useful in studying discrete protein populations associated with detergent-resistant membranes, and their potential interactions in cell signaling. PMID- 17870180 TI - Contour-propagation algorithms for semi-automated reconstruction of neural processes. AB - A new technique, "serial block face scanning electron microscopy" (SBFSEM), allows for automatic sectioning and imaging of biological tissue with a scanning electron microscope. Image stacks generated with this technology have a resolution sufficient to distinguish different cellular compartments, including synaptic structures, which should make it possible to obtain detailed anatomical knowledge of complete neuronal circuits. Such an image stack contains several thousands of images and is recorded with a minimal voxel size of 10-20 nm in the x- and y-direction and 30 nm in z-direction. Consequently, a tissue block of 1 mm(3)(the approximate volume of the Calliphora vicina brain) will produce several hundred terabytes of data. Therefore, highly automated 3D reconstruction algorithms are needed. As a first step in this direction we have developed semi automated segmentation algorithms for a precise contour tracing of cell membranes. These algorithms were embedded into an easy-to-operate user interface, which allows direct 3D observation of the extracted objects during the segmentation of image stacks. Compared to purely manual tracing, processing time is greatly accelerated. PMID- 17870179 TI - A new grading system evaluating bleeding scale in filament perforation subarachnoid hemorrhage rat model. AB - The endovascular perforation rodent model for experimental subarachnoid hemorrhage (SAH) studies is criticized for lack of control over bleeding. Presently, there is no practical grading system to categorize the severity of SAH depending on the amount of blood. We outline a simple and objective novel SAH grading system by examining the subarachnoid blood clots in the basal cisterns, and evaluate for correlation with neurological status and cerebral vasospasm. Effects of simvastatin, known to reduce vasospasm, were examined using this grading system. Seventy-seven adult male Sprague-Dawley rats were divided randomly into three groups: sham-operated (n=24), SAH (n=32), and SAH+simvastatin (n=25). High-resolution brain pictures were used to grade the severity of SAH and categorize animals into mild, moderate and severe groups. The SAH grades were compared with neurological scores and internal carotid artery parameters such as diameter, perimeter and wall thickness at 24h. Two investigators verified the grading system independently. The SAH grade showed linear correlation functionally with neurological status (r=0.42, p<0.01) and morphometrically with the degree of vasospasm (|r|>0.7, p<0.01), and also between two independent investigators (r=0.937, p<0.001). Simvastatin improved neurological score in moderate and severe (p<0.05) but not mild SAH groups (p=0.28). This grading system has the potential to be adopted for SAH experimental rodent models. PMID- 17870181 TI - Development of an improved canine model of percutaneous spinal cord compression injury by balloon catheter. AB - We developed a minimally invasive canine model of spinal cord injury (SCI). A balloon catheter was inserted into the epidural space via the lumbosacral space, and inflated between L2 and L3 for 30 or 60 min under fluoroscopic guidance. Motor function after SCI was assessed using modified Tarlov scale. All seven dogs showed complete paraplegia after the procedure, neurological problems were evident and the modified Tarlov scores remained at zero after the SCI procedure; no improvement in clinical signs was observed. The dogs underwent 3T MR imaging at 3 days and 1 year after SCI. Histopathologic examinations were conducted at 2 weeks, 12 weeks and 1 year after SCI. In the present study, we described an animal model of minimally invasive spinal cord injury using a balloon catheter without laminectomy under fluoroscopic guidance. And, this percutaneous spinal cord compression injury model has many potential applications. The described percutaneous spinal cord compression injury model offers a new means of administering SCI and has many potential applications. PMID- 17870182 TI - Neuromuscular electrical stimulation induced forelimb movement in a rodent model. AB - Upper extremity neuromuscular electrical stimulation (FNS) has long been utilized as a neuroprosthesis to restore hand-grasp function in individuals with neurological disorders and injuries. More recently, electrical stimulation is being used as a rehabilitative therapy to tap into central nervous system plasticity. Here, we present initial development of a rodent model for neuromuscular stimulation induced forelimb movement that can be used as a platform to investigate stimulation-induced plasticity. The motor points for flexors and extensors of the shoulder, elbow, and digits were identified and implanted with custom-built stimulation electrodes. The strength-duration curves were determined and from these curves the appropriate stimulation parameters required to produce consistent isolated contraction of each muscle with adequate joint movement were determined. Using these parameters and previous locomotor EMG data, stimulation was performed on each joint muscle pair to produce reciprocal flexion/extension movements in the shoulder, elbow, and digits, while 3D joint kinematics were assessed. Additionally, co-stimulation of multiple muscles across multiple forelimb joints was performed to produce stable multi-joint movements similar to those observed during reach-grasp-release movements. Future work will utilize this model to investigate the efficacy and underlying mechanisms of forelimb neuromuscular stimulation therapy to promote recovery and plasticity after neural injury in rodents. PMID- 17870183 TI - The impact of altruistic behaviors for children and grandchildren on major depression among parents and grandparents in the United States: a prospective study. AB - BACKGROUND: Although previous studies have suggested that altruistic behaviors are beneficial for mental health, few studies have examined the impact of altruistic behaviors for children and grandchildren (ABC) on the mental health of parents and grandparents using a longitudinal study design. It is needed to test whether paternal and maternal ABC prevent the development of mental health problems in later life. METHOD: The association between three types of ABC (informal assistance, emotional support, financial support) in 1995-1996 and major depression (MD) in 1998 were examined using a nationally representative longitudinal study in the US (the National Survey of Midlife Development in the United States (MIDUS) in 1995-1996 and the MIDUS Psychological Experience Follow Up study in 1998, N=724). RESULTS: Moderate amounts of informal assistance and financial support by fathers/grandfathers, but not by mothers/grandmothers, showed a protective effect on MD 2-3 years later, holding parents/grandparents and children covariates. Emotional support was not associated with MD for both sexes after adjusting for covariates. LIMITATION: The sample size in this study was relatively small and not all possible covariates were adjusted. The effect of children's/grandchildren's responses for ABC on the development of parental MD was not examined. CONCLUSION: The impact of ABC on MD in 2-3 years varies depending on the types of ABC and the sex of parents/grandparents. Moderate amounts of informal assistance and financial support had a protective effect on MD in later life among fathers/grandfathers, but not among mothers/grandmothers. PMID- 17870184 TI - Subsyndromal depressive symptoms in patients with bipolar and unipolar disorder during clinical remission. AB - BACKGROUND: Subsyndromal depressive symptoms seem to be quite prevalent in mood disorders although very few studies have assessed them in patients considered to be in remission by clinical and psychometric criteria. This study sought to evaluate the presence of subsyndromal depressive symptoms in bipolar and unipolar patients in clinical remission. METHODS: One-hundred seventy-six patients with DSM-IV bipolar (62 bipolar I, 58 bipolar II) or unipolar mayor depression (n=58) in clinical remission and 60 healthy subjects were assessed using several psychometric instruments including the 17 items Hamilton Depression Rating Scale (HDRS). To be considered in clinical remission patients assessed with the Clinical Impression for Bipolar Disorder-Modified (CGI-BP-M) had to be stable for 6 months and scoring 6 or less in the Young Mania Rating Scale (YMRS) and 8 or less in the HDRS. RESULTS: Both Unipolar Disorder (UD) and Bipolar Disorder (BD) patients in clinical remission presented statistically significant higher HRSD scores, than healthy subjects. The HRSD scores were statistically higher in UD patients under remission than in BD patients. The subsyndromal symptoms more strongly associated with a clinical diagnosis of either UD or BD were Depressed Mood, Somatic Anxiety, Impact on Work and Activities, Psychic Anxiety, Gastrointestinal and Somatic Symptoms, Retardation during the Interview and Genital Symptoms. CONCLUSION: Subsyndromal depressive symptoms are present in affective disorder patients, both UD and BD, who apparently are in clinical remission. Remitted unipolar patients may have more residual symptoms than bipolar patients, particularly in items related to anxiety and somatic complaints. PMID- 17870185 TI - Influence of the probiotic Bacillus cereus var. toyoi on the intestinal immunity of piglets. AB - In a feeding trial, sows and piglets were fed with the probiotic bacterium Bacillus cereus var. toyoi as a feed additive, and the effects on immune cell populations were examined. The development of the gut immune system was determined for piglets at the ages of 14, 28, 35 and 56 days post partum. Tissue samples of the Jejunum and the continuous Peyer's patch were used for enumeration of intraepithelial lymphocyte populations by fluorescence activated flow cytometry and fluorescence microscopy. Both independent methods of investigation led to similar results: the population of intraepithelial CD8+ T cells was significantly enhanced in the probiotic group piglets (p< or =0.05), and the numbers of gammadelta T cells tended to be higher in the intestinal epithelium (p<0.1) at the time of weaning (day 28). Lamina propria lymphocytes were also influenced by the treatment. Application of B. cereus var. toyoi resulted in significantly more CD25+ lymphocytes and gammadelta T cells in the probiotic group post-weaning. The occurrence of pathogenic Escherichia coli serogroups was also less frequent in the feces of piglets from the probiotic group. The finding that the CD8+ T cell population in the intestinal mucosa showed changes on day 28 indicated that the influence of B. cereus var. toyoi supplementation on the intestinal immune system started before weaning, an observation supported by changes in the intestinal microflora observed during the suckling-period. The results suggest that feeding of B. cereus var. toyoi to sows may result in beneficial effects on piglet health status independent of their feed supplementation. PMID- 17870186 TI - Vestibular system in infants after systemic aminoglycoside therapy. AB - OBJECTIVES: The ototoxic action of systemic therapy with aminoglycoside antibiotics leading to the loss of inner ear hair cells is well recognized. The mitochondria-mediated pathway of apoptosis may play a role in inducing the apoptosis of vestibular hair cells due to aminoglycoside toxicity. Aminoglycosides are, nevertheless, routinely used for treatment of vital infections in neonatologic departments. Although there is a strong supposition that aminoglycosides can influence the vestibular function in infants, the routine examination of the infants' inner ear does not include vestibular tests. The purpose of the present study was to evaluate vestibular function in a group of infants prior to and after administration of systemic aminoglycosides, using caloric tests and vestibular-evoked myogenic potentials (VEMPs). METHODS: VEMPs and auditory brainstem responses were recorded and caloric stimulation was performed in 68 infants aged 2.5-3.5 months: 40 healthy controls and 28 infants after therapy with amikacin, 15mg/(kgday) in three doses. The therapy duration varied from 10 to 14 days. In 18 infants antibiotic therapy was administered for a respiratory infection, and in 10 for sepsis. Infants with other risk factors of inner ear damage and treated with more than one ototoxic drug were excluded from the study. The tests were performed on the day of admission to hospital and repeated on the day of discharge. RESULTS: The results of all tests were normal on admission. On the day of discharge, no reaction to caloric stimulation was elicited in six patients and no VEMPs were recorded in four subjects. Hearing thresholds were normal in all the individuals during both examinations. CONCLUSIONS: The vestibular organ in infants after systemic therapy with amikacin may be damaged more frequently than the cochlear organ. The horizontal canal is more vulnerable to aminoglycosides, as compared to the saccule. The vestibular organ should be routinely examined in infants after systemic treatment with aminoglycosides. PMID- 17870187 TI - Comparison of transient evoked otoacoustic emissions and distortion product otoacoustic emissions when screening hearing in preschool children in a community setting. AB - OBJECTIVE: The first purpose of this study was to compare transient evoked otoacoustic emissions (TEOAE) with distortion product otoacoustic emissions (DPOAE) to determine if they resulted in equivalent signal-to-noise ratios (SNRs) when used for hearing screening in a preschool population in a community setting. The second purpose was to determine if the OAE methods would result in equivalent pass/refer rates. The third purpose was to determine the agreement between the pass/refer rates from a tympanometric screening and the pass/refer rates from each OAE method. METHODS: Thirty-three preschool children ages 4 months to 4 years, 4 months were tested using DPOAE and TEOAE. The frequencies 800-4000Hz were compared. The tympanometric gradient was obtained from a tympanogram done on each ear. A multivariate statistic was used to compare the emission SNR from both methods. A chi(2) statistic was used to compare the pass/refer rates from both methods. The agreement between the pass/refer rates from the OAE screens and from the tympanometric gradient were compared. RESULTS: TEOAE and DPOAE SNRs were significantly different in the low frequency however, there were no significant differences found in the high frequencies. There were no significant pass/refer differences found between the methods at any frequency. When comparing the agreement between the OAE methods with the tympanometry, both methods produced nearly equivalent agreement with tympanometric gradient. However, the overall correspondence between OAE findings and tympanometry was not perfect. CONCLUSIONS: Both methods are effective and especially equivalent in the high frequencies and can be recommended for use in a preschool population in the field. Tympanometric gradient disagreed with both OAE screening results about 25% of the time. Finally, our study also found that higher refer rates can be expected when young (<3 years) preschool children are included in the screen. PMID- 17870188 TI - One-step multiplex real-time PCR assay to analyse the latency patterns of Epstein Barr virus infection. AB - Epstein-Barr virus (EBV) establishes a latent infection with three types of viral gene expression. These latency types can be distinguished by the expression patterns of EBV nuclear antigen (EBNA)1, EBNA2, latent membrane protein (LMP)1, and LMP2. The EBV lytic cycle is initiated by the transcription of the EBV immediate early BZLF1 gene, which can be used to distinguish between a latent and a lytic infection. In this study, a one-step multiplex real-time PCR assay was developed to quantify the EBNA1, EBNA2, LMP1, LMP2, and BZLF1 expression levels simultaneously by relative quantification. To validate this assay, the quantitation of viral gene transcription was performed in EBV-positive B, T, and natural killer cell lines. Because of its rapidity, sensitivity, and specificity, this new assay can be used for quantitative analyses of the latency patterns of EBV infection and the switch from latency to lytic viral replication. PMID- 17870189 TI - An improved DNA isolation method and PCR protocol for efficient detection of multicomponents of begomovirus in legumes. AB - A relatively inexpensive protocol for the detection of genomic components of whitefly-transmitted begomoviruses in symptomatic legumes in the field is described. The method involves extraction with a modified CTAB buffer containing beta-mercaptoethanol upto 5% and sodium chloride concentration from 1.4 to 2.0M. Using this method PCR amplifiable DNA could be extracted from mature leaves of legume hosts rich in polyphenols, tannins and polysaccharides. The non-coding region and full-length DNA A, DNA B components of yellow mosaic viruses were consistently amplifiable from 97 samples, out of 136 tested in PCR reaction, employing primers specific for intergenic regions and full-length genome. The system is robust and the protocol is useful for the detection and identification of begomoviruses infecting grain legumes. PMID- 17870190 TI - Effects of algal-produced neurotoxins on metabolic activity in telencephalon, optic tectum and cerebellum of Atlantic salmon (Salmo salar). AB - Neurotoxins from algal blooms have been reported to cause mortality in a variety of species, including sea birds, sea mammals and fish. Farmed fish cannot escape harmful algal blooms and their potential toxins, thus they are more vulnerable for exposure than wild stocks. Sublethal doses of the toxins are likely to affect fish behaviour and may impair cognitive abilities. In the present study, changes in the metabolic activity in different parts of the Atlantic salmon (Salmo salar) brain involved in central integration and cognition were investigated after exposure to sublethal doses of three algal-produced neurotoxins; saxitoxin (STX), brevetoxin (BTX) and domoic acid (DA). Fish were randomly selected to four groups for i.p. injection of saline (control) or one of the neurotoxins STX (10 microg STX/kg bw), BTX (68 microg BTX/kg bw) or DA (6 mg DA/kg bw). In addition, 14C-2 deoxyglucose was i.m. injected to measure brain metabolic activity by autoradiography. The three regions investigated were telencephalon (Tel), optic tectum (OT) and cerebellum (Ce). There were no differences in the metabolic activity after STX and BTX exposure compared to the control in these regions. However, a clear increase was observed after DA exposure. When the subregions with the highest metabolic rate were pseudocoloured in the three brain regions, the three toxins caused distinct differences in the respective patterns of metabolic activation. Fish exposed to STX displayed similar patterns as the control fish, whereas fish exposed to BTX and DA showed highest metabolic activity in subregions different from the control group. All three neurotoxins affected subregions that are believed to be involved in cognitive abilities in fish. PMID- 17870191 TI - Neuropeptide W is expressed in the noradrenalin-containing cells in the rat adrenal medulla. AB - Neuropeptide W (NPW) is an endogenous ligand for GPR7, a member of the G-protein coupled receptor family. NPW plays an important role in the regulation of both feeding and energy metabolism, and is also implicated in modulating responses to an acute inflammatory pain through activation of the hypothalamus-pituitary adrenal axis. GPR7 mRNA has been shown to be expressed in the hypothalamus, pituitary gland and adrenal cortex. Similarly, NPW expression has been demonstrated in the brain and pituitary gland. However, the precise distribution of NPW-producing cells in the adrenal gland remains unknown. The aim of this study was to explore the distribution and localization of NPW immunoreactivity in the rat adrenal gland. Total RNA was prepared from the hypothalamus, pituitary gland and adrenal gland. RT-PCR revealed the expression of NPW mRNA in these tissues, while in situ hybridization demonstrated the presence of NPW mRNA in the adrenal medulla. When immunohistochemistry was performed on sections of adrenal gland, NPW-like immunoreactivity (NPW-LI) was observed in the medulla but not in the cortex. Moreover, NPW-LI was found to be co-localized in cells which expressed dopamine beta hydroxylase but not phenylethanolamine-N methyltransferase. The finding that NPW is expressed in noradrenalin-containing cells in the adrenal medulla suggests that it may play an important role in endocrine function in the adrenal gland. PMID- 17870192 TI - Molecular identification and characterization of the dog motilin receptor. AB - Motilin, a 22-amino acid peptide hormone secreted by endocrine cells of the intestinal mucosa, plays an important role in the regulation of gastrointestinal motility. The actions of motilin agonists have been extensively investigated in dogs due to physiological similarities between the dog and human alimentary tracts. The amino acid sequence of the dog motilin receptor, however, was previously unknown. We have cloned a cDNA from dog stomach corresponding to the motilin receptor. The deduced protein shared 71% and 72% sequence identity with the human and rabbit motilin receptors, respectively. Expression of the dog motilin receptor in CHO cells promoted the typical cellular responses to the agonists, motilin and erythromycin. The rank order of potency determined for these agonists was similar to that found for the human motilin receptor, with motilin being more potent than erythromycin. Immunohistochemistry of the dog stomach revealed that the motilin receptor was localized in neuronal cell bodies and fibers. This is the first study detailing the cloning, expression, and functional characterization of the dog motilin receptor. Determination of the full sequence and functional properties of the dog motilin receptor will provide useful information enabling us to interpret previous and future studies of motilin agonists in dogs. PMID- 17870193 TI - Developmental expression and serotonergic regulation of relaxin 3/INSL7 in the nucleus incertus of rat brain. AB - Relaxin 3 or insulin like peptide 7 has been identified as a new member of the insulin/relaxin superfamily. We recently reported that relaxin 3 was dominantly expressed in the brain, particularly in neurons of the nucleus incertus (NI) of the median dorsal tegmental pons and that it might act as a neurotransmitter. In the present study we investigated the developmental expression and serotonergic regulation of relaxin 3 gene in the rat brain. Relaxin 3 mRNA appeared at embryonic day 18 in the near region of the fourth ventricle, and was shown to have increased its density and the number of expressing neurons by in situ hybridization and RT-PCR examination. Relaxin 3 peptide was detected after birth by immunocytochemistry. Since the NI is located just caudal to the dorsal raphe nucleus where abundant serotonin (5-HT) neurons are present, we examined if 5-HT effects on the expression of relaxin 3. Relaxin 3 gene expression in the NI significantly increased after 5-HT depletion by p-chlorophenylalanine (PCPA) administration. We also observed the 5-HT1A receptor localization in relaxin 3 positive neurons of the NI. This result suggests that 5-HT negatively regulates the expression of relaxin 3 gene in the NI. The function of relaxin 3 neurons in the brain is influenced by the serotonergic activity. PMID- 17870195 TI - Identification and functional analysis of a novel ligand for G protein-coupled receptor, Neuromedin S. AB - We identified a novel 36-amino acid neuropeptide in rat brain as an endogenous ligand for the G protein-coupled receptors FM-3/GPR66 and FM-4/TGR-1, which were identified to date as the neuromedin U (NMU) receptors, and designated this peptide neuromedin S (NMS) because it was specifically expressed in the suprachiasmatic nucleus (SCN) of the hypothalamus. NMS shared a C-terminal core structure with NMU. NMS mRNA was highly expressed in the central nervous system, spleen and testis. In rat brain, NMS expression was restricted to the ventrolateral portion of the SCN and has a diurnal peak under light/dark cycling, but remains stable under constant darkness. Intracerebroventricular (ICV) administration of NMS in rats induced nonphotic type phase shifts in the circadian rhythm of locomotor activity. ICV injection of NMS also decreased 12-h food intake during the dark period in rats. This anorexigenic effect was more potent than that observed with the same dose of NMU. ICV administration of NMS increased proopiomelanocortin (POMC) mRNA expression in the arcuate nucleus (Arc) and corticotropin-releasing hormone mRNA in the paraventricular nucleus, and induced c-Fos expression in the POMC neurons in the Arc. These findings suggest that NMS is implicated in the regulation of circadian rhythm and feeding behavior. PMID- 17870196 TI - Engineering photorespiration in chloroplasts: a novel strategy for increasing biomass production. AB - Photosynthetic carbon metabolism is rate limiting in C3 plants because of a competing process: photorespiration. Photorespiration lowers the energy efficiency of photosynthesis by metabolizing glycolate produced by the oxygenate activity of Rubisco. The chloroplasts of Arabidopsis thaliana have recently been reported to contain a novel respiratory pathway that converts glycolate directly to glycerate and thus increases productivity by improving photosynthesis in transgenic plants. This pathway promises to widen the applicability of the approach to other C3 plants. PMID- 17870197 TI - Global VOR gain adaptation during near fixation to foveal targets. AB - Long-term rotational vestibulo-ocular (VOR) adaptation occurs during systematic dysmetria between visual and vestibular afferents, adjusting eye-rotation angular velocity to re-establish retinal stability of the visual field. Due to translational motion of the eyes during head rotation, VOR gain is higher when fixating near objects. The current study measures VOR in humans before and after 6 min of exposure to a foveal near-target during sinusoidal whole-body rotation at 0.45 Hz. All of six participants showed post-exposure increases in open-loop VOR gain after fixating near targets, demonstrating a mean modulation increase of open-loop VOR gain from 0.86 before adaptation to 1.2 after adaptation. We discuss a number of theoretical and applied implications. PMID- 17870198 TI - The tryptophan hydroxylase 1 (TPH1) gene and risk of schizophrenia: a moderate scale case-control study and meta-analysis. AB - Serotonin (5-hydroxytryptamine [5-HT]) may be implicated in both the pathophysiology of schizophrenia and in mediating atypical antipsychotic drug effects. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme involved in the synthesis of 5-HT. Some genetic variants of the TPH1 gene have been tested for their associations with schizophrenia, but with conflicting results. To assess whether TPH1 is implicated in vulnerability to schizophrenia, we conducted a case control association study (409 patients and 440 controls) for six single nucleotide polymorphisms in Japanese subjects and performed an updated meta analysis. There were no significant associations between the polymorphisms or haplotypes of TPH1 and schizophrenia in our Japanese subjects. Our updated meta analysis, which included six population-based case-control studies, suggests the possible involvement of the TPH1 218A allele in susceptibility to schizophrenia. To draw any conclusion, however, further studies using larger sample sizes should be carried out in various ethnic populations. PMID- 17870199 TI - Possible involvement of psychrotolerant Enterobacteriaceae in blown pack spoilage of vacuum-packaged raw meats. AB - Recent investigations of blown pack spoilage in New Zealand chilled vacuum packaged meats have found moderate to high numbers of Enterobacteriaceae in the spoilage flora, but no clostridia, such as C. estertheticum and C. gasigenes, that are usually associated with blown pack spoilage. This study showed that pyschrotolerant Enterobacteriaceae produced gas in a lamb homogenate model under anaerobic conditions and that these organisms could cause blown pack spoilage of vacuum-packaged chilled meats. Significant gas production was observed with the majority of the psychrotolerant Enterobacteriaceae strains tested including presumptive species of Enterobacter, Serratia, Hafnia and Rahnella. However, no gas was produced in lamb homogenates inoculated with presumptive species of Ewingella americana or Yersinia enterocolitica. Gas production was also confirmed in vacuum-packaged lamb shoulders stored at 4 degrees C for 21 days after being inoculated with individual representative Enterobacteriaceae isolates. Biochemical characterisation proved to be more useful than genotype-based typing of 16S rRNA genes for discriminating different psychrotolerant Enterobacteriaceae from naturally contaminated meat microflora. PMID- 17870200 TI - Hybrid semi-parametric mathematical systems: bridging the gap between systems biology and process engineering. AB - Systems biology is an integrative science that aims at the global characterization of biological systems. Huge amounts of data regarding gene expression, proteins activity and metabolite concentrations are collected by designing systematic genetic or environmental perturbations. Then the challenge is to integrate such data in a global model in order to provide a global picture of the cell. The analysis of these data is largely dominated by nonparametric modelling tools. In contrast, classical bioprocess engineering has been primarily founded on first principles models, but it has systematically overlooked the details of the embedded biological system. The full complexity of biological systems is currently assumed by systems biology and this knowledge can now be taken by engineers to decide how to optimally design and operate their processes. This paper discusses possible methodologies for the integration of systems biology and bioprocess engineering with emphasis on applications involving animal cell cultures. At the mathematical systems level, the discussion is focused on hybrid semi-parametric systems as a way to bridge systems biology and bioprocess engineering. PMID- 17870201 TI - Physiology and pharmacology of the brushtail possum gastrointestinal tract: relationship to the human gastrointestinal tract. AB - Oral formulations are typically based on studies from eutherian animal models. This review introduces information relating to oral formulations for a marsupial species, the Australian brushtail possum (Trichosurus vulpecula) that has arisen from research into new methods for controlling this species - a major vertebrate pest in New Zealand. Morphologically, the gastrointestinal tract of the brushtail possum is similar to that of hindgut fermenting eutherian species, but there are some striking differences in function. Limited data suggests that the pharmacokinetics and bioavailability of administered drugs are similar to that in eutherian species, but there is some evidence that possums may have specific mechanisms for handling the intake of plant toxins and xenobiotics. The development of oral formulations for a free-ranging pest species presents several challenges above those encountered in the development of therapeutic formulations for humans and domestic animals. Use of a marsupial animal model may lead to new strategies for oral formulations in humans. PMID- 17870202 TI - The chick embryo and its chorioallantoic membrane (CAM) for the in vivo evaluation of drug delivery systems. AB - Mammalian models are frequently used for preclinical evaluation of new drug delivery systems (DDS). However, valid mammalian models are expensive, time consuming, and not easy to set up and evaluate. Furthermore, they are often linked to administrative burden with respect to ethical and legal aspects. The present review outlines the possibilities and limitations of using the hen's embryo, and specifically its chorioallantoic membrane (CAM), as an alternative to mammalian models for the evaluation of DDS. Features of the CAM, the anatomy of the embryo, and the blood were investigated to assess properties of the drug carriers such as toxicity and biocompatibility, as well as the activity, toxicity, biodistribution and pharmacokinetics of the drug. The simplicity, rapidity, and low cost of the different assays that can be performed with chick embryos strengthen the interest of routinely using this model in pharmaceutical technology research. It is concluded that there is a big potential for using chick embryos in screening procedures of formulation candidates, thus establishing an intermediate step between in vitro cellular tests and preclinical mammalian models. PMID- 17870203 TI - Effects of rhubarb extract on radiation induced lung toxicity via decreasing transforming growth factor-beta-1 and interleukin-6 in lung cancer patients treated with radiotherapy. AB - BACKGROUND: Radiation induced lung toxicity (RILT) is the main adverse effect in the radiation therapy of lung cancer. However, the optimal management of RILT has not been defined. In this paper, we investigated the effects of rhubarb extract on RILT, pulmonary function (PF), transforming growth factor-beta-1 (TGF-beta1), and interleukin-6 (IL-6) in lung cancer patients treated with radiotherapy. PATIENTS AND METHODS: We conducted a randomized, double-blind, placebo-controlled trial. Eighty consecutive patients were randomly enrolled into two groups: trial group and control group. The trial group received three-dimensional conformal radiation therapy (3D-CRT) plus rhubarb (at a dose of 20 mg kg(-1) once a day) for 6 weeks. The control group received 3D-CRT plus a placebo containing starch for 6 weeks. Plasma TGF-beta1 and serum IL-6 were measured in all patients before, every 2 weeks during, and at 6 weeks after the completion of the treatment. RILT and PF were evaluated at 6 weeks and 6 months after the end of the treatment, respectively. The differences of TGF-beta1, IL-6, RILT, and PF between the two groups were analysed. RESULTS: The incidence of RILT in the trial group was significantly lower than that in the control group at 6 weeks and 6 months after treatment (32.4% versus 56.7% at week 6, and 27.0% versus 52.8% at month 6, both P<0.05). The plasma TGF-beta1 levels in the trial group were significantly lower than that in the control group during and after the treatment (P<0.05 or 0.01, respectively). The serum IL-6 levels in the trial group were significantly lower than that in the control group during the treatment (all P<0.01). The forced vital capacity (FVC), forced expiratory volume at 1s (FEV1) at 6 weeks and the diffusion capacity for carbon monoxide (DLCO) at 6 months in the trial group were significantly improved compared to the control group (P<0.05 or 0.01, respectively). CONCLUSIONS: The rhubarb extract significantly attenuated RILT and improved PF, probably by decreasing the level of TGF-beta1 and IL-6. These results may be of value for the prophylaxis of RILT, but the exact mechanisms underlying these prophylactic effects remain to be further explored. PMID- 17870204 TI - Polymorphisms in hMLH1 and risk of early-onset lung cancer in a southeast Chinese population. AB - DNA mismatch repair (MMR) plays an important role in maintaining genome stability. Defects in MMR genes have been involved in several types of sporadic and hereditary cancers. hMLH1 is considered one of central members of the MMR pathway. We conducted a hospital-based case-control study to investigate associations of common variations in the hMLH1 gene and risk of lung cancer. A total of 500 cases and 517 controls were genotyped for seven SNPs in hMLH1. Overall, the rs1799977 I219V polymorphism was marginally associated with the risk of lung cancer (P=0.055). This association was much stronger in younger patients (P=0.01; odds ratio, 5.28; 95% CI 1.45-19.21) and lung squamous cell carcinoma (P=0.006; odds ratio, 3.65; 95% CI 1.44-9.24). These findings indicate that the hMLH1 rs1799977 polymorphism may contribute to the etiology of early-onset lung cancer as well as some specific subtype of lung cancer. Larger association studies are warranted to validate our findings and mechanistic studies are needed to elucidate the underlying molecular mechanisms of the association. PMID- 17870205 TI - Modeling the mechanisms for uptake and translocation of dioxane in a soil-plant ecosystem with STELLA. AB - Knowledge of mechanisms for uptake, translocation, and accumulation of soil contaminants in plants is essential to successful applications of the phytoremediation technique. Analysis and evaluation of these mechanisms would be greatly facilitated by the availability of a dynamic model that can predict soil contaminant uptake by roots, transport from roots through stems to leaves, and accumulation in plant during the transport process. In this study, a dynamic model for uptake and translocation of contaminants from a soil-plant ecosystem (UTCSP) was developed using the STELLA modeling tool. The structure of UTCSP consists of time-dependent simultaneous upward transport, accumulation, and transpiration of water and contaminants in the soil-plant-atmosphere continuum, which was driven by water potential gradients among soils, roots, stems, leaves, and atmosphere. The UTCSP model was calibrated using the experimental measurements and applied to predict phytoremediation of 1,4-dioxane from a sandy soil by a poplar tree. Simulation results showed that about 20% of 1,4-dioxane was removed from the soil by the poplar tree in 90 days. The simulations further revealed that while the mass of 1,4-dioxane in the poplar tree increased consecutively with time, the rates of water and 1,4-dioxane uptake and translocation in the roots, stems, and leaves have a typical diurnal distribution pattern: increasing during the day and decreasing during the night, resulting from daily variations of plant water potentials that were caused by leaf water transpiration. This study suggests that the UTCSP model is a useful tool for estimating phytoremediation of contaminants in the soil-plant ecosystems. PMID- 17870206 TI - The impact of screening, brief intervention, and referral for treatment on emergency department patients' alcohol use. AB - STUDY OBJECTIVE: We determine the impact of a screening, brief intervention, and referral for treatment (SBIRT) program in reducing alcohol consumption among emergency department (ED) patients. METHODS: Patients drinking above National Institute of Alcohol Abuse and Alcoholism low-risk guidelines were recruited from 14 sites nationwide from April to August 2004. A quasiexperimental comparison group design was used in which control and intervention patients were recruited sequentially at each site. Control patients received a written handout. The intervention group received the handout and a brief intervention, the Brief Negotiated Interview, to reduce unhealthy alcohol use. Follow-up surveys were conducted at 3 months by telephone using an interactive voice response system. RESULTS: Of 7,751 patients screened, 2,051 (26%) exceeded the low-risk limits set by National Institute of Alcohol Abuse and Alcoholism; 1,132 (55%) of eligible patients consented and were enrolled (581 control, 551 intervention). Six hundred ninety-nine (62%) completed a 3-month follow-up survey, using the interactive voice response system. At follow-up, patients receiving a Brief Negotiated Interview reported consuming 3.25 fewer drinks per week than controls (coefficient [B] -3.25; 95% confidence interval [CI] -5.76 to -0.75), and the maximum number of drinks per occasion among those receiving Brief Negotiated Interview was almost three quarters of a drink less than controls (B -0.72; 95% CI -1.42 to -0.02). At-risk drinkers (CAGE <2) appeared to benefit more from a Brief Negotiated Interview than dependent drinkers (CAGE >2). At 3-month follow up, 37.2% of patients with CAGE less than 2 in the intervention group no longer exceeded National Institute of Alcohol Abuse and Alcoholism low-risk limits compared with 18.6% in the control group (delta 18.6%; 95% CI 11.5% to 25.6%). CONCLUSION: SBIRT appears effective in the ED setting for reducing unhealthy drinking at 3 months. PMID- 17870207 TI - Over-expression of neurotensin high-affinity receptor 1 (NTS1) in relation with its ligand neurotensin (NT) and nuclear beta-catenin in inflammatory bowel disease-related oncogenesis. AB - We investigated the expression of the neurotensin high-affinity receptor 1 (NTS1) during inflammatory bowel disease (IBD)-related colorectal oncogenesis, in colonic samples from 30 patients with IBD-related adenocarcinomas, dysplasias, and inflammatory mucosa (IM). The percentage of NTS1-positive epithelial cells progressively increased from the inflammatory condition to adenocarcinoma and was significantly higher in adenocarcinomas than in IM (p=0.0169). In parallel, the percentage of neurotensin (NT)-positive epithelial cells increased during the IBD related oncogenesis. Finally, as NTS1 is a ss-catenin inducible gene, we found that a number of preneoplastic lesions and adenocarcinomas co-expressed NTS1 and beta-catenin without NT expression. Therefore, this study suggests two pathways of NTS1 overexpression during IBD-related oncogenesis: one triggered by NT overexpression, and a second associated with an activation of the APC/beta catenin pathway, these two pathways being not mutually exclusive. PMID- 17870209 TI - 4-thiazolidinone--a biologically active scaffold. AB - The broad and potent activity of 4-thiazolidinones has established it as one of the biologically important scaffolds. This article is an effort to highlight the importance of the 4-thiazolidinones in the present context and promise they hold for the future. PMID- 17870208 TI - Thyroid function, the risk of dementia and neuropathologic changes: the Honolulu Asia aging study. AB - Thyroid dysfunction is associated with cognitive impairment and dementia, including Alzheimer's disease (AD). It remains unclear whether thyroid dysfunction results from, or contributes to, Alzheimer pathology. We determined whether thyroid function is associated with dementia, specifically AD, and Alzheimer-type neuropathology in a prospective population-based cohort of Japanese-American men. Thyrotropin, total and free thyroxine were available in 665 men aged 71-93 years and dementia-free at baseline (1991), including 143 men who participated in an autopsy sub-study. During a mean follow-up of 4.7 (S.D.: 1.8) years, 106 men developed dementia of whom 74 had AD. Higher total and free thyroxine levels were associated with an increased risk of dementia and AD (age and sex adjusted hazard ratio (95% confidence interval) per S.D. increase in free thyroxine: 1.21 (1.04; 1.40) and 1.31 (1.14; 1.51), respectively). In the autopsied sub-sample, higher total thyroxine was associated with higher number of neocortical neuritic plaques and neurofibrillary tangles. No associations were found for thyrotropin. Our findings suggest that higher thyroxine levels are present with Alzheimer clinical disease and neuropathology. PMID- 17870210 TI - Synthesis, properties, and perspectives of gem-diphosphono substituted-thiazoles. AB - A series of substituted arylidene thiazoles were allowed to react with Wittig Horner (WH) reagent, tetraethyl methyl-1,1-bisphosphonate, to produce via Michael addition reaction the corresponding heteroarylmethylenebisphosphonates (BPs) in different yields according to the experimental conditions. Acid hydrolysis of the new BPs was undertaken to obtain the corresponding bisphosphonic acids. Prediction and the in vivo activity of the products in the rat adjuvant model are also discussed in terms of structure-activity relationships (SAR). PMID- 17870211 TI - Synthesis and antimycobacterial evaluation of substituted pyrazinecarboxamides. AB - Unsubstituted, halogenated and/or alkylated pyrazine-2-carboxylic acid amides connected via -CONH- bridge with substituted anilines were synthesized using currently known synthetic pathways. The synthetic approach, analytical, spectroscopic, lipophilicity and biological data of 20 newly synthesized compounds are presented. Structure-activity relationships among the chemical structures, the antimycobacterial, antifungal, photosynthesis inhibiting and antialgal activity of the evaluated substituted N-phenylpyrazine-2-carboxamides are discussed. 5-tert-Butyl-6-chloro-N-(3-trifluoromethylphenyl)pyrazine-2 carboxamide (19) has shown the highest activity against Mycobacterium tuberculosis H(37)Rv (MIC=3.13 microg/mL). The highest antifungal effect against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for N-(3-trifluoromethylphenyl)pyrazine-2-carboxamide (14, MIC=62.5 micromol/mL). The highest reduction of chlorophyll content in Chlorella vulgaris was found for pyrazine-2-carboxylic acid (3-trifluoromethylphenyl)amide (9, IC(50)=12.1 micromol/L). PMID- 17870212 TI - Xanthine oxidase-activated prodrugs of thymidine phosphorylase inhibitors. AB - Thymidine phosphorylase (TP) is over-expressed in various tumour types and plays an important role in tumour angiogenesis, growth, invasion and metastasis. The enzymatic activity of TP is required for the angiogenic effect of TP, therefore, inhibitors of TP are of significant interest in cancer chemotherapy. A series of xanthine oxidase (XO) activated prodrugs of known inhibitors of TP have been designed and synthesized with the ultimate intent of improving tumour selectivity and pharmacokinetic characteristics. These prodrugs were not inhibitors of TP, but were selectively oxidized by XO at C-2 and/or C-4 of the uracil ring moiety to generate the desired TP inhibitor. Molecular modelling of both the TP inhibitors and XO-activated prodrugs rationalized their binding in the active site of the human TP crystal structure. PMID- 17870213 TI - Development of an anti-cotinine vaccine to potentiate nicotine-based smoking cessation strategies. AB - Nicotine replacement therapies (NRT) have limited success in smoking cessation. The efficacy of nicotine may be compromised by its main metabolite, cotinine. An anti-cotinine vaccine to remove this antagonism could enhance the efficacy of NRT. We show that cotinine is a weak nicotinic agonist and decreases responses to nicotine, consistent with antagonism through receptor desensitisation. trans-4 Thiol cotinine was coupled to tetanus toxoid, and rats immunised repeatedly. Vaccination raised antibodies specific for cotinine that do not recognise other metabolites or nicotine. Increased serum cotinine concentrations following nicotine administration indicate sequestration of cotinine by antibodies, encouraging further evaluation of this vaccine in behavioural models of nicotine addiction and relapse. PMID- 17870215 TI - Timing of hepatitis B vaccination: its effect on vaccine response in health care workers. AB - We assessed the effect of timing and other biological variables on immune response among health care workers (HCW) vaccinated with hepatitis B vaccine. A total of 2.058 HCW received three doses and were tested for anti-HBs within 6 months. 92.2% of the HCW had evidence of seroprotection. Multivariable analysis showed that controlling for age, the estimated non-response OR associated with a delayed second dose was 2.16 (95% CI: 1.46, 3.18, p=0.004). We found a decreasing response rate with increasing age. Particular attention should be given to those HCW who are late for the second vaccine dose and to older subjects. PMID- 17870214 TI - Development and preclinical evaluation of an alphavirus replicon particle vaccine for cytomegalovirus. AB - We used a replication-incompetent, single-cycle, alphavirus replicon vector system to produce virus-like replicon particles (VRP) expressing the extracellular domain of human cytomegalovirus (CMV) glycoprotein B or a pp65/IE1 fusion protein. Efficient production methods were scaled to produce pilot lots and clinical lots of each alphavirus replicon vaccine component. The vaccine induced high-titered antibody responses in mice and rabbits, as measured by ELISA and CMV neutralization assays, and robust T-cell responses in mice, as measured by IFN-gamma ELISPOT assay. A toxicity study in rabbits showed no adverse effects in any toxicology parameter. These studies support clinical testing of this novel CMV alphavirus replicon vaccine in humans. PMID- 17870216 TI - Generation of an attenuated H5N1 avian influenza virus vaccine with all eight genes from avian viruses. AB - In the face of disease outbreaks in poultry and the potential pandemic threat to humans caused by the highly pathogenic avian influenza viruses (HPAIVs) of H5N1 subtype, improvement in biosecurity and the use of inactivated vaccines are two main options for the control of this disease. Vaccine candidates of influenza A viruses of H5N1 subtype have been generated in several laboratories by plasmid based reverse genetics with hemagglutinin (HA) and neuraminidase (NA) genes from the epidemic strains of avian viruses in a background of internal genes from the vaccine donor strain of human strains, A/Puerto Rico/8/34 (PR8). These reassortant viruses containing genes from both avian and human viruses might impose biosafety concerns, also may be do if C4/F AIV would be a live attenuated vaccine or cold-adaptive strain vaccine. In order to generate better and safer vaccine candidate viruses, we genetically constructed attenuated reassortant H5N1 influenza A virus, designated as C4/F AIV, by plasmid-based reverse genetics with all eight genes from the avian strains. The C4/F AIV virus contained HA and NA genes from an epidemic strain A/Chicken/Huadong/04 (H5N1) (C4/H5N1) in a background of internal genes derived from a low pathogenic strain of A/Chicken/F/98(H9N2). The reassortant virus was attenuated by removal of the multibasic amino acid motif in the HA gene by mutation and deletion (from PQRERRRKKR (downward arrow) G to PQIETR (downward arrow) G). The intravenous pathogenicity index (IVPI) of C4/F AIV virus was 0, whereas that of the donor virus C4/H5N1 was 3.0. The virus HA titer of C4/H5N1 in the allantoic fluid from infected embryonated eggs was as high as 1:2048. The inactivated vaccine prepared from the reassortant virus C4/F AIV-induced high HI titer in vaccinated chickens and gave 100% protection when challenged with highly pathogenic avian influenza virus of H5N1 subtype. PMID- 17870217 TI - Sea to land transfer of anthropogenic radionuclides to the North Wales coast, Part I: external gamma radiation and radionuclide concentrations in intertidal sediments, soil and air. AB - Previous projects specifically aimed at performing radiological assessments in the vicinity of North Wales, investigating the presence and transfer of radionuclides from sea to land, were in 1986 and 1989. Since then, changes have occurred in the radioactive discharges from the British Nuclear Group Sellafield site. Annual discharges of (137)Cs, (238)Pu, (239,340)Pu and (241)Am have decreased markedly whereas, up until recent years, discharges of (99)Tc have increased. It is therefore desirable to quantify current transfer processes of radionuclides in the North Wales region and thus provide an update on 15-year-old studies. A field campaign was conducted collecting soil samples from 10 inland transects and air particulates on air filters from three High Volume Air Samplers, along the northern coast of Wales at Amlwch, Bangor Pier and Flint. Complementary field data relating to external gamma dose rates were collected at the soil sites. The field data generated for (137)Cs, (238)Pu, (239,340)Pu and (241)Am were consistent with what had been reported 15 years previously. Therefore, there has been no increase in the supply of these Sellafield-derived radionuclides to the terrestrial environment of the North Wales coast. The (99)Tc data in sediments were consistent with reported values within annual monitoring programmes, however, a relatively high activity concentration was measured in one sediment sample. This site was further investigated to determine the reason why such a high value was found. At present there is no clear evidence as to why this elevated concentration should be present, but the role of seaweed and its capacity in accumulating (99)Tc and transferring it to sediment is of interest. The analysis of the field samples for (99)Tc, (137)Cs, (238)Pu, (239,240)Pu and (241)Am has provided a data set that can be used for the modelling of the transfer of anthropogenic radionuclides from sea to land and its subsequent radiological implications and is reported in an accompanying paper. PMID- 17870218 TI - Oral mucosal disease: pemphigus. AB - Pemphigus defines a group of rare mucocutaneous autoimmune diseases of which pemphigus vulgaris (PV) is the most common. The aetiology and pathogenesis of PV are not completely clear, but there is a fairly strong genetic background: ethnic groups such as Ashkenazi Jews and people of Mediterranean and Indian origin are particularly susceptible and there is a link to HLA class II alleles. The initiating event in PV is not clear, but circulating IgG autoantibodies develop, directed particularly against the intercellular cadherin desmoglein 3 (Dsg3) in desmosomes of stratified squamous epithelium. Oral lesions often herald the disease and are initially vesiculobullous, but they rupture readily to leave ulcers. Involvement of other mucosa and skin is almost inevitable and PV is potentially life threatening. The diagnosis is confirmed by biopsy with histological examination and immunostaining. Management is largely by systemic immunosuppression with corticosteroids, usually azathioprine or other agents, but newer treatments with potentially fewer adverse effects look promising. PMID- 17870219 TI - Breast feeding practices and views among diabetic women: a retrospective cohort study. AB - OBJECTIVE: to explore the pattern and experiences of breast-feeding practices among diabetic women. DESIGN: retrospective cohort study using maternal records and postal questionnaires in a Baby-Friendly hospital. PARTICIPANTS: diabetic mothers including women with gestational diabetes, and type 1 and 2 diabetes mellitus. FINDINGS: from the total group of respondents, 81.9% intended to breast feed. The actual breast feeding rates were 81.9% at birth, 68.1% at 2 weeks and 28.7% at 6 months postpartum. Major themes that were identified from women's experiences included information and advice, support vs. pressure, classification and labelling, and expectations. CONCLUSIONS: more than two-thirds of the diabetic women intended to breast feed and actually did breast feed in this study. For both the total study population and the type 1 and 2 diabetics alone, more than half were still breast feeding at 2 weeks postpartum, and approximately one-third were still breast feeding at 6 months postpartum. IMPLICATIONS FOR PRACTICE: structured support, provided for women through Baby-Friendly initiatives, was appreciated by the diabetic women in this study. The extent to which this support influenced the highly successful breast feeding practices in this group of women needs focused investigation. The need for a delicate balancing act between pressure and advice in order to prevent coercion was noted. PMID- 17870220 TI - Co-contraction during passive movements of the knee joint in children with cerebral palsy. AB - BACKGROUND: Co-contraction is an impairment commonly reported in children with cerebral palsy. However, co-contraction has not been investigated during passive movements which may be used to assess spasticity in children with cerebral palsy. The purpose of this study was to examine the frequency of co-contraction and the relationship between reflex activity and co-contraction during passive movements of the knee joint in children with cerebral palsy. METHODS: Twenty children with cerebral palsy participated in this study. One set of ten continuous passive movements from 90 degrees of knee flexion to 25 degrees of knee flexion and from 25 degrees of knee flexion to 90 degrees of knee flexion was completed at 15 degrees /s, 90 degrees /s, and 180 degrees /s. The mean percentage of the range of motion of each movement and mean percentage of the number of movements which exhibited electromyographic activity of the vastus lateralis, medial hamstrings, and co-contraction were calculated for each set of movements. FINDINGS: The number of the movement repetitions and the percentage of the range of motion which exhibited co-contraction were considerable regardless of the direction and speed of motion. Significant positive correlations were found between the percentage of the passive range of motion with medial hamstrings activation, vastus lateralis activation, and co-contraction during passive movements into both knee flexion and knee extension at a velocity of 15 degrees /s, 90 degrees /s, and 180 degrees /s (P<0.001). INTERPRETATION: Co-contraction commonly occurs during passive movements of the knee in children with cerebral palsy. The presence of co-contraction may influence measurements of spasticity which use passive movements to assess spasticity. PMID- 17870221 TI - Factors affecting hip range of motion in surface replacement arthroplasty. AB - BACKGROUND: Surface replacement arthroplasty aims to re-create normal hip biomechanics; however the pathoanathomy of the hip, prosthetic component design, surgical technique and other factors may have a significant impact on the range of motion restoration attained following surface replacement arthroplasty. However, there is paucity of information on the effect of such factors. METHODS: A computerized three-dimensional hip model was created from preoperative computerized tomography images of a patient who was scheduled for a surface replacement arthroplasty. The effects of the femoral component size, translation and orientation on the range of motion were analysed as was the effect of increasing the seating depth and modification of the version of the acetabular component. FINDINGS: Increasing the femoral component size led to global improvement in range of motion while translation increased range of motion in one direction but reduced it in the opposite direction. Change in the femoral component orientation had minimal effects on range of motion in comparison to the effect of changes in the version of the acetabular component. Increasing the seating depth of the acetabulum only caused reduced range of motion in internal rotation in 90 degrees flexion. INTERPRETATION: To restore hip range of motion, surgeons performing surface replacement arthroplasty should aim to reproduce the natural femoral head-neck offset. Although increasing the femoral component size may achieve this, more acetabular bone will be resected. Knowing the specific zones of impingement of each arc of movement, selective translation of the femoral component or femoral neck osteoplasty can restore femoral neck offset in more critical areas without affecting acetabular bone stock. Over deepening of the acetabulum or leaving rim osteophytes should also be avoided to prevent impingement. PMID- 17870222 TI - Removal of phenolic estrogen pollutants from different sources of water using molecularly imprinted polymeric microspheres. AB - The efficiency and effects of using Bisphenol A-molecularly imprinted polymeric microspheres (MIPMs) to remove phenolic estrogens from different sources of water were evaluated. MIPMs prepared by precipitation polymerization removed a group of phenolic estrogens from different kinds of water selectively and effectively. The highest removal efficiency was observed at pH=5. Fifty millimoles per litre ions or 10mg/L humid acid improved removal efficiency. MIPMs were more suitable to remove trace estrogens in large volume than high concentration of estrogens in small volume. The removal efficiency of spiked tap water, lake water and river water were better than that of distilled water. Hundred milligrams of MIPMs had higher removal selectivity and efficiency than those of 100mg or 300mg activated carbons. Moreover, MIPMs can be re-used for at least 30 times without losing any removal efficiency. MIPMs provided a selective, simple, reliable and practicable solution to remove trace phenolic estrogens from different sources of water. PMID- 17870223 TI - Findings of preserved implicit attention in methamphetamine dependent subjects. AB - Long-term methamphetamine (MA) abuse is associated with a wide range of deficits on explicit tasks of selective attention. Less is known however about the effects of MA abuse on implicit measures of attention. Accordingly, we used a computerized spatial priming task to assess implicit attentional processes in 54 MA dependent subjects (mean age=37.04+/-8.9 years) and 32 healthy controls without history of any form of substance abuse (mean age=33.63+/-7.05 years). The MA dependent subjects had been drug-abstinent a minimum of 3 weeks with a mean duration of MA use of 13.27+/-7.75 years. The MA dependent subjects did not differ significantly from controls on either inhibitory priming [p=.37] or facilitory priming) [p=.69]. This result comports with our earlier findings of intact object-based priming in MA dependent individuals and suggests that intact priming effects extend across spatial domains. Further, this pattern of sparing suggests that cortical brain systems typically supporting implicit attentional functioning are relatively intact in long-term MA dependent individuals whereas brain systems supporting explicit attentional processes are affected. PMID- 17870224 TI - Dietary diphenyl diselenide reduces the STZ-induced toxicity. AB - Oxidative stress is implicated in the pathogenesis of diabetes mellitus. Selenium supplementation has some benefits in experimental models of diabetes mellitus. This study evaluated whether dietary diphenyl diselenide, a simple synthetic organoselenium compound with antioxidant properties, reduces the streptozotocin (STZ)-induced toxicity. STZ-induced diabetic rats were fed with either standard and diphenyl diselenide (10 ppm) supplemented diets. In experimental trials, dietary diphenyl diselenide significantly decreased mortality rate (p<0.05) induced by STZ treatment. No correlation between this effect and glycemic levels were found. Diphenyl diselenide intake also promoted an increase in vitamin C, SH levels (liver, kidney and blood) and in catalase (liver and kidney) activity, which were decreased in STZ-treated rats. In enzyme assays, diphenyl diselenide supplementation caused a significant improvement in platelets NTPDase and 5' nucleotidase activities in STZ-induced diabetic rats when compared to the control and diabetic groups (p<0.05). Nevertheless, this supplementation did not modify the inhibition induced by STZ in delta-ALA-D activity. Our findings suggest that diphenyl diselenide compound showed beneficial effects against the development of diabetes by exhibiting antioxidant properties. PMID- 17870225 TI - Mediator complexes and eukaryotic transcription regulation: an overview. AB - Mediator is an essential component of the RNA polymerase II-mediated transcription machinery. This component plays a key role both in the stimulation of basal transcription and in the regulation of eukaryotic mRNA synthesis. The Saccharomyces cerevisiae Mediator complex was the first to be studied and consists of at least 20 different subunits with multiple activities. Afterwards, its subunit composition was determined and related functions of C. elegans, Drosophila and mammalian complexes show a striking evolutionary conservation both of the structure and function from yeast to man. Recently, yeast studies strongly suggest additional roles for Mediator in coordinating transcription initiation with downstream transcriptional events in the coding region of genes; consequently, new models of recruitment-coupled regulation have been indicated. Further studies on transcription machinery should expand our knowledge of the pathways in which variant components of Mediator, or variant proteins interacting directly or in complexes, represent risk factors for complex inheritable disease. PMID- 17870226 TI - Strict normoglycaemic blood glucose levels in the therapeutic management of patients within 12h after cardiac arrest might not be necessary. AB - AIM OF THE STUDY: The admission blood glucose level after cardiac arrest is predictive of outcome. However the blood glucose levels in the post-resuscitation period, that are optimal remains a matter of debate. We wanted to assess an association between blood glucose levels at 12h after restoration of spontaneous circulation and neurological recovery over 6 months. MATERIALS AND METHODS: A total of 234 patients from a multi-centre trial examining the effect of mild hypothermia on neurological outcome were included. According to the serum glucose level at 12h after restoration of spontaneous circulation, quartiles (Q) were generated: Median (range) glucose concentrations were for QI 100 (67-115 mg/dl), QII 130 (116-143 mg/dl), QIII 162 (144-193 mg/dl) and QIV 265 (194-464 mg/dl). RESULTS: In univariate analysis there was a strong non-linear association between blood glucose and good neurological outcome (odds ratio compared to QIV): QI 8.05 (3.03-21.4), QII 13.41 (4.9-36.67), QIII 1.88 (0.67-5.26). After adjustment for sex, age, "no-flow" and "low-flow" time, adrenaline (epinephrine) dose, history of coronary artery disease and myocardial infarction, and therapeutic hypothermia, this association still remained strong: QI 4.55 (1.28-16.12), QII 13.02 (3.29-49.9), QIII 1.37 (0.38-5.64). CONCLUSION: There is a strong non linear association of survival with good neurological outcome and blood glucose levels 12h after cardiac arrest even after adjusting for potential confounders. Not only strict normoglycaemia, but also blood glucose levels from 116 to 143 mg/dl were correlated with survival and good neurological outcome, which might have an important therapeutic implication. PMID- 17870227 TI - Early ventilation in traumatic brain injury. AB - While airway and ventilatory compromise are significant concerns following traumatic brain injury (TBI), there is little data supporting an aggressive approach to airway management by prehospital personnel, and a growing number of reports suggesting an association between early intubation and increased mortality. Recent clinical and experimental data suggest that hyperventilation is an important contributor to these adverse outcomes in TBI patients. Various mechanisms appear to be responsible for the worsened outcomes, including hemodynamic, cerebrovascular, immunologic and cellular effects. Here, relevant experimental and clinical data regarding the impact of ventilation on TBI are reviewed. In addition, experimental data regarding potential mechanisms for the adverse effects of hyperventilation and hypocapnia on the injured brain are presented. Finally, the limited data regarding the impact of hypoventilation and hypercapnia on outcome from TBI are discussed. PMID- 17870228 TI - Integrated resuscitation simulators should retain "basic" options. PMID- 17870229 TI - Clinical neurophysiology of aging brain: from normal aging to neurodegeneration. AB - Physiological brain aging is characterized by a loss of synaptic contacts and neuronal apoptosis that provokes age-dependent decline of sensory processing, motor performance, and cognitive function. Neural redundancy and plastic remodelling of brain networking, also secondary to mental and physical training, promotes maintenance of brain activity in healthy elderly for everyday life and fully productive affective and intellectual capabilities. However, age is the main risk factor for neurodegenerative disorders such as Alzheimer's disease (AD) that impact on cognition. Oscillatory electromagnetic brain activity is a hallmark of neuronal network function in various brain regions. Modern neurophysiological techniques including electroencephalography (EEG), event related potential (ERP), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS) can accurately index normal and abnormal brain aging to facilitate non-invasive analysis of cortico-cortical connectivity and neuronal synchronization of firing and coherence of rhythmic oscillations at various frequencies. The present review provides a perspective of these issues by assaying different neurophysiological methods and integrating the results with functional brain imaging findings. It is concluded that discrimination between physiological and pathological brain aging clearly emerges at the group level, with applications at the individual level also suggested. Integrated approaches utilizing neurophysiological techniques together with biological markers and structural and functional imaging are promising for large-scale, low-cost and non invasive evaluation of at-risk populations. Practical implications of the methods are emphasized. PMID- 17870230 TI - Brain iron metabolism: neurobiology and neurochemistry. AB - New findings obtained during the past years, especially the discovery of mutations in the genes associated with brain iron metabolism, have provided key insights into the homeostatic mechanisms of brain iron metabolism and the pathological mechanisms responsible for neurodegenerative diseases. The accumulated evidence demonstrates that misregulation in brain iron metabolism is one of the initial causes for neuronal death in some neurodegenerative disorders. The errors in brain iron metabolism found in these disorders have a multifactorial pathogenesis, including genetic and nongenetic factors. The disturbances of iron metabolism might occur at multiple levels, including iron uptake and release, storage, intracellular metabolism and regulation. It is the increased brain iron that triggers a cascade of deleterious events, leading to neuronal death in these diseases. In the article, the recent advances in studies on neurochemistry and neuropathophysiology of brain iron metabolism were reviewed. PMID- 17870231 TI - Sustainability, substance flow management and time. Part I Temporal analysis of substance flows. AB - Flows of chemical substances need to be managed in a sustainable way. Sustainable development as a whole and the sustainable management of substance flows in particular are both time issues. These include the importance of the dynamics of substance flows and the way these interconnect with the use of resources, the avoidance of environmental pollution, and their effects on health and food production. Another prerequisite for the proper management of substance flows is justice within and between generations. This requires a systematic approach and a systematic analysis of the issues as well as of the actions to be taken. One tool for such a systematic approach is temporal analysis. It brings the temporal aspects of the substances themselves and of their intended use, as well as factors affecting the stakeholders, such as decision makers, producers and consumers, into focus. In the past, timing factors were rarely taken into account. Knowledge of the temporal dynamics of substance flows and their resultant outcomes, as well as of their interaction with ecological, economic and social systems, is a basic requirement for successful substance flow management. The need to include temporal aspects into substance flow management and how to do so is outlined here. Included are not only politicians but also practitioners and scientists who must explicitly take into account adequate time scales, points in time, breaks and other forms of time in planning and acting. PMID- 17870232 TI - Editorial comment on the long term (5-years) objective TVT success rate does not depend on predictive factors at multivariate analysis: a multicentre retrospective study. PMID- 17870233 TI - Glucocorticoids modulate NF-kappaB-dependent gene expression by up-regulating FKBP51 expression in Newcastle disease virus-infected chickens. AB - FK506-binding protein 51(FKBP51, coded by FKBP5) is a co-chaperone molecule that interacts with the chaperone HSP90 and the glucocorticoid receptor (GR) in an inactive GR complex. It is a negative regulator of glucocorticoid action and is replaced by the positive regulator, FK506-binding protein 52 (FKBP52, coded by FKBP4) when hormone binds to GR, which renders the GR complex active. In this study, we found that the expression of FKBP51 mRNA in 12 organs of Newcastle disease virus (NDV)-infected chickens was robustly induced. The level of corticosterone in NDV-infected chickens was also elevated, approximately 2- to 6.5-fold in the organs compared to non-infected control chickens. The induction of FKBP51 mRNA expression was reproduced by dexamethasone treatment, indicating a role for glucocorticoids in the systemic induction of FKBP51 mRNA expression. In chicken UMNSAH/DF-1 cells, nuclear factor kappaB (NF-kappaB) was activated in an FKBP51-dependent manner. Regulation of the three NF-kappaB-dependent, anti apoptotic genes, bcl-2, bcl-x and bfl-1/A1 was investigated in UMNSAH/DF-1 cells. Dexamethasone treatment of UMNSAH/DF-1 cells resulted in up-regulation of bcl-2, and down-regulation of bcl-x and bfl-1/A1. Expression of FKBP51 also resulted in down-regulation of bfl-1/A1, but had no effect on bcl-2 and bcl-x, suggesting the involvement of glucocorticoid-FKBP51-NF-kappaB signaling in the regulation of expression of bfl-1/A1 in UMNSAH/DF-1 cells. We observed organ-specific up- or down-regulation of expression of, bcl-2, bcl-x and bfl-1/A1 in NDV-infected and dexamethasone-treated chickens. Differential regulation of bfl-1/A1, bcl-2 and bcl-x upon NDV-infection and dexamethasone treatment suggests that additional factors are involved in the regulation of these genes. These results suggest that systemic elevation of FKBP51 in NDV-infected chickens activates NF-kappaB, which cooperates with other factors to regulate the expression of NF-kappaB-dependent genes. PMID- 17870234 TI - Demyelinating plaque imitates an intramedullary tumour. AB - An isolated spinal demyelinating lesion is very rare and almost always associated with multiple sclerosis. There are only a few reports of biopsy or resection of MS-associated lesions. Sometimes the radiological and the histopathological findings can lead to a false diagnosis of a tumour. A 15-year-old girl presented with a progressive spastic tetraparesis and various associated clinical symptoms. Magnetic resonance imaging (MRI) suggested a possible intramedullary tumour extending from C4 to C7 and the need for surgical intervention. There was no previous neurological or other history and the brain MRI was normal. The performing surgeons based their procedures on oncological criteria. The extracted lesion was finally diagnosed as a demyelinating plaque. The postoperative course was uneventful without deterioration of the neurological status and the young patient improved completely after 4-months of rehabilitation. After an 8-year follow-up, the patient remains in remission and free of neurological defects. Apart from the radiological findings, the CSF exam as well as the evoked potentials does not suggest a diagnosis of MS. A demyelinating plaque in the cervical spinal cord can occasionally imitate a cervical intramedullary tumour leading to an operation. Such lesions underscore the sensitivity of present-day lesion detection procedures. An addition of a MS work up could be beneficial in some cases of intramedullary tumours without a typical history, although in the case presented this type of workup was negative. PMID- 17870235 TI - Own-sex effects in emotional memory for faces. AB - The amygdala is known to be critical for the enhancement of memory for emotional, especially negative, material. Importantly, some researchers have suggested a sex specific hemispheric lateralization in this process. In the case of facial expressions, another important factor that could influence memory success is the sex of the face, which could interact with the emotion depicted as well as with the sex of the perceiver. Whether this is the case remains unknown, as all previous studies of sex difference in emotional memory have employed affective pictures. Here we directly explored this question using functional magnetic resonance imaging in a subsequent memory paradigm for facial expressions (fearful, happy and neutral). Consistent with our hypothesis, we found that the hemispheric laterality of the amygdala involvement in successful memory for emotional material was influenced not only by the sex of the subjects, as previously proposed, but also by the sex of the faces being remembered. Namely, the left amygdala was more active for successfully remembered female fearful faces in women, whereas in men the right amygdala was more involved in memory for male fearful faces. These results confirm the existence of sex differences in amygdala lateralization in emotional memory but also demonstrate a subtle relationship between the observer and the stimulus in this process. PMID- 17870236 TI - TDAG51 in the anterior temporal neocortex of patients with intractable epilepsy. AB - TDAG51 (T cell death-associated gene 51) is an apoptosis-associated protein. Our aim was to investigate TDAG51 expression in the anterior temporal neocortex of patients with intractable epilepsy (IE), and then to discuss the possible role of TDAG51 in IE. Tissue samples from the anterior temporal neocortex of 33 patients who had surgery for IE were used to detect TDAG51 expression by immunohistochemistry, immunofluorescence, and Western blotting. We compared these tissues with nine histologically normal anterior temporal lobes from intracranial hypertension patients who had decompression procedures. TDAG51 was mainly expressed in the cytoplasm of neurons and glial cells. TDAG51 in IE was significantly higher than that in the controls. These findings were consistently observed using Western blotting, immunofluorescence, and immunohistochemistry techniques. TDAG51 in patients with IE was significantly higher when compared with levels in the controls. This finding suggests TDAG51 is consistent with a possible role of this gene in the evolution of the pathology in IE. PMID- 17870237 TI - The effects of intra-oral pain on motor cortex neuroplasticity associated with short-term novel tongue-protrusion training in humans. AB - To determine if short-term (15 min) training in a novel tongue-task is associated with rapid neuroplasticity of the tongue primary motor area (MI) in the human cerebral cortex, and if intra-oral tonic pain affects the tongue MI neuroplasticity and tongue-task training performance. Nine healthy volunteers (7 men, 2 women, mean age 24+/-1.1 years) participated in two cross-over training sessions in which the application to the tongue of the algesic chemical capsaicin (1%) or vehicle cream was randomized. Prior to and again immediately after 15 min of training in a tongue-protrusion task, transcranial magnetic stimulation (TMS) was applied to the MI in each session and motor evoked potentials (MEPs) were recorded in the tongue musculature and the first dorsal interosseous (FDI) muscle (as control). Neuroplasticity of the tongue MI, as reflected in a significantly enhanced TMS-MEP stimulus-response curve and reduced MEP threshold, was observed after the vehicle session but not after the capsaicin session. Subjects' overall mean performance scores were significantly higher in the vehicle session than in the capsaicin session. MI neuroplasticity may rapidly occur in association with successful performance in novel tongue-task training, but intra-oral tonic pain interferes with these effects. These findings suggest that nociceptive input modulates MI neuroplasticity associated with novel motor training and may impair the ability to learn a new motor task. PMID- 17870238 TI - Comment on Ballantyne and LaForge, Opioid dependence and addiction during opioid treatment of chronic pain. Pain 2007;129:235-55. PMID- 17870239 TI - Brain excitability in migraine: hyperexcitability or inhibited inhibition? PMID- 17870240 TI - Dual influence of the striatum on neuropathic hypersensitivity. AB - We studied whether striatal alpha(2)-adrenoceptors or N-methyl-d-aspartate (NMDA) receptors influence descending regulation of neuropathic hypersensitivity in the rat by microinjecting an alpha(2)-adrenoceptor agonist or NMDA-receptor antagonist into the dorsal striatum in animals with a spinal nerve ligation induced neuropathy. Hypersensitivity was assessed in the hind limb by monofilaments and paw pressure test. Various neurotransmitter receptor antagonists were administered into the striatum or intrathecally to determine striatal and spinal neurotransmitters mediating the modulatory influence. The results indicate that the striatum has a dual effect on neuropathic hypersensitivity via two distinct pathways descending to the spinal cord. First, hypersensitivity is reduced following activation of noradrenergic alpha(2) adrenoceptors and downstream dopamine D2 receptors in the striatum. This antihypersensitivity effect is predominantly ipsilateral and it descends via parallel dopaminergic and serotoninergic pathways to act on spinal dopamine D2 and 5-HT(1A) receptors, respectively. Second, tonic activation of striatal NMDA receptors promotes hypersensitivity by suppressing spinal GABAergic inhibition. The antihypersensitivity actions induced by striatal drug administrations were not associated with motor effects as suggested by lack of effect on the threshold of the uninjured limb or amplitude of the innocuous H-reflex. Involvement of striatal dopamine D2 receptors in the noradrenergic pain inhibitory circuitry may explain why disorders causing hypofunction of the striatal dopaminergic system, such as in Parkinson's disease, have been associated with pain. Furthermore, our findings indicate that striatal NMDA receptors provide a tonic supramedullary drive for medullospinal facilitatory influence that is known to be of importance for neuropathic hypersensitivity. PMID- 17870241 TI - Breast burns are not benign: long-term outcomes of burns to the breast in pre pubertal girls. AB - Chest burns in pre-pubescent girl are commonly seen in paediatric burn units. These patients are at risk of significant long-term problems with scarring and breast development requiring reconstructive surgery many years after the initial burn. Admissions to our unit over a 20-year period were reviewed to determine the frequency of these burns. Patients whose burns required surgical debridement and split skin grafting, and who would now be post-pubertal were included in the study. We attempted to trace and contact these patients and were able to find 13 out of 22 patients, of whom 11 agreed to participate. The mechanism of injury in six was scalds and the other five had flame burns. Mean age of patients with scald was 18 months and for flame burns 4 years 8 months. These women required a variety of reconstructive procedures to improve breast appearance including contracture releases, dermabrasion, breast augmentation and contralateral breast reduction. Girls burned as young children require follow-up and appropriate referral long after the burn to ensure good cosmetic results are achieved during and after puberty. PMID- 17870242 TI - Second-degree chemical burns of the scrotum caused by application of home-made ointment for relief of epididymal pain. PMID- 17870243 TI - 'Practical guidelines for nutritional management of burn injury and recovery'--a guideline based on expert opinion but not including RCTs. PMID- 17870244 TI - Use of the Internet by burns patients, their families and friends. AB - INTRODUCTION: The Internet has also become an increasingly important source of health-related information. However, with this exponential increase comes the problem that although the volume of information is huge, the quality, accuracy and completeness of the information are questionable, not only in the field of medicine. Previous studies of single medical conditions have suggested that web based health information has limitations. The aim of this study was to evaluate Internet usage among burned patients and the people accompanying them to the outpatient clinic. METHODS: A customised questionnaire was created and distributed to all patients and accompanying persons in the adult and paediatric burns clinics. This investigated computer usage, Internet access, usefulness of Internet search and topics searched. RESULTS: Two hundred and ten people completed the questionnaire, a response rate of 83%. Sixty three percent of responders were patients, parents 21.9%, spouses 3.3%, siblings, children and friends the remaining 10.8%. Seventy seven percent of attendees had been injured within the last year, 11% between 1 and 5 years previously, and 12% more than 5 years previously. Seventy four percent had computer and Internet access. Twelve percent had performed a search. Topics searched included skin grafts, scarring and scar management treatments such as pressure garments, silicone gel and massage. DISCUSSION: This study has shown that computer and Internet access is high, however a very small number actually used the Internet to access further medical information. Patients with longer standing injuries were more likely to access the Internet. Parents of burned children were more frequent Internet users. As more burn units develop their own web sites with information for patients and healthcare providers, it is important to inform patients, family members and friends that such a resource exists. By offering such a service patients are provided with accurate, reliable and easily accessible information which is appropriate to their needs. PMID- 17870245 TI - Peptide-based radiopharmaceuticals and cytotoxic conjugates: potential tools against cancer. AB - A hope for the diagnosis and treatment of cancer is the development of new tumor specific peptide-based radiopharmaceuticals. The overexpression of many peptide receptors on human tumors makes such receptors an attractive potential target for diagnostic imaging and radiotherapy with specifically designed radiolabeled peptides. The use of solid-phase peptide synthesis, and the availability of a wide range of bifunctional chelating agents for the convenient radiolabeling of bioactive peptides with different radionuclides have produced a wide variety of medicinally useful peptide radiopharmaceuticals. A few of these peptides, such as somatostatin, bombesin, cholecystokinin/gastrin, neurotensin and vasoactive intestinal peptide are currently under investigation for their possible clinical applications in nuclear oncology. This article presents the recent development in radiolabeled small peptides, with major emphasis on somatostatin and bombesin analogs. PMID- 17870246 TI - Mice overexpressing chemokine ligand 2 (CCL2) in astrocytes display enhanced nociceptive responses. AB - Recent findings demonstrate that chemokines, and more specifically CC chemokine ligand 2 (CCL2 or monocyte chemoattractant protein-1), play a major role in pain processing. In the present study, we assess nociceptive responses of mice that overexpressed CCL2 under control of glial fibrillary acidic protein promoter (CCL2 tg). In models of acute nociception CCL2 tg mice demonstrated significantly enhanced nociceptive behavior relative to wild-type controls in responses to both thermal (hot plate) and chemical (formalin test) stimulus modalities. There were no differences in mechanical allodynia in the partial sciatic nerve ligation model, in terms of either magnitude or duration of the allodynic response; however, both groups responded to the maximal extent measurable. In a model of inflammatory pain, elicited by intraplantar administration of complete Freund's adjuvant (CFA), CCL2 tg mice displayed both greater edema and thermal hyperalgesia compared with control mice. In control mice, edema and hyperalgesia returned to baseline values 5-7 days post CFA. However, in CCL2 tg mice, thermal hyperalgesia was significantly different from baseline up to 3 weeks post CFA. Parallel to these enhanced behavioral responses CCL2 serum levels were significantly greater in CCL2 overexpressing mice and remained elevated 7 days post CFA. Consequently, proinflammatory cytokine mRNA expression (IL-1beta, IL-6, and TNFalpha) levels were greater in skin, dorsal root ganglia (DRG), and spinal cord, whereas the anti-inflammatory cytokine (IL-10) level was lower in skin and DRG in CCL2 overexpressing mice than in control mice. Taken together with data from CCR2-deficient mice, these present data confirm a key role of CCL2/CCR2 axis in pain pathways and suggest that inhibiting this axis may result in novel pain therapies. PMID- 17870247 TI - Differentiating embryonic stem-derived neural stem cells show a maturation dependent pattern of voltage-gated sodium current expression and graded action potentials. AB - A population of mouse embryonic stem (ES)-derived neural stem cells (named NS cells) that exhibits traits reminiscent of radial glia-like cell population and that can be homogeneously expanded in monolayer while remaining stable and highly neurogenic over multiple passages has been recently discovered. This novel population has provided a unique in vitro system in which to investigate physiological events occurring as stem cells lose multipotency and terminally differentiate. Here we analysed the timing, quality and quantity of the appearance of the excitability properties of differentiating NS cells which have been long-term expanded in vitro. To this end, we studied the biophysical properties of voltage-dependent Na(+) currents as an electrophysiological readout for neuronal maturation stages of differentiating NS cells toward the generation of fully functional neurons, since the expression of neuronal voltage-gated Na(+) channels is an essential hallmark of neuronal differentiation and crucial for signal transmission in the nervous system. Using the whole cell and single channel cell-attached variations of the patch-clamp technique we found that the Na(+) currents in NS cells showed substantial electrophysiological changes during in vitro neuronal differentiation, consisting mainly in an increase of Na(+) current density and in a shift of the steady-state activation and inactivation curves toward more negative and more positive potentials respectively. The changes in the Na(+) channel system were closely related with the ability of differentiating NS cells to generate action potentials, and could therefore be exploited as an appropriate electrophysiological marker of ES-derived NS cells undergoing functional neuronal maturation. PMID- 17870248 TI - Axonal lesion-induced microglial proliferation and microglial cluster formation in the mouse. AB - Microglia are innate immune cells and form the first line of defense of the CNS. Proliferation is a key event in the activation of microglia in acute pathology, and has been extensively characterized in rats, but not in mice. In this study we investigated axonal-lesion-induced microglial proliferation and surface antigen expression in C57BL/6 mice. Transection of the entorhino-dentate perforant path projection results in an anterograde axonal and a dense terminal degeneration that induces a region-specific activation of microglia in the dentate gyrus. Time course analysis showed activation of microglial cells within the first week post lesion and cell counting demonstrated a significant 1.6-fold increase in microglial numbers 24 h post-lesion reaching a maximal 3.8-fold increase 3 days post-lesion compared with controls. Double staining for the microglial macrophage antigen-1 and the proliferation marker bromodeoxyuridine, injected 1 h prior to perfusion, showed that lesion-reactive microglia accounted for the vast majority of proliferating cells. Microglia proliferated as soon as 24 h after lesion and 25% of all microglial cells were proliferating 3 days post-lesion. Immunofluorescence double staining showed that most activated, proliferating microglia occurred in multicellular clusters and co-expressed the intercellular adhesion molecule-1 and the hematopoietic stem cell marker cluster of differentiation 34. In conclusion, this study extends observations of axonal lesion-induced microglial proliferation in rats to mice, and provides new information on early microglial proliferation and microglial cluster formation and surface antigen expression in the mouse. PMID- 17870249 TI - Activation of the androgen receptor alters the intracellular calcium response to glutamate in primary hippocampal neurons and modulates sarco/endoplasmic reticulum calcium ATPase 2 transcription. AB - Androgens have been shown to have a number of effects on hippocampal function. Although androgen receptors (AR) are found at high levels in hippocampal neurons, the intracellular mechanisms responsible for androgen's actions are unknown. If androgens were capable of altering internal calcium concentration ([Ca(2+)](i)), they could influence a variety of intracellular signaling pathways, maintain neuronal homeostasis and Ca(2+) induced excitotoxicity. In the present study, calcium imaging was used to measure the [Ca(2+)](i) in rat primary hippocampal neurons treated with either the AR agonist dihydrotestosterone (DHT), DHT+flutamide (AR antagonist), flutamide alone, or vehicle for 24 h and subsequently presented with an excitatory glutamate stimulus. In the absence of glutamate stimulation, DHT treatment caused a significant upward shift in baseline [Ca(2+)](i) when compared with neurons from all other groups. Glutamate had a greater effect on [Ca(2+)](i) in DHT-treated neurons and DHT-treated neurons returned to baseline levels significantly faster than all other groups. Cyclopiazonic acid, an inhibitor of sarco/endoplasmic reticulum calcium ATPase (SERCA) had a larger response in DHT-treated neurons compared with controls, suggesting increased Ca(2+) stores in DHT-treated neurons. In all cases the effects of DHT were blocked by treatment with flutamide indicating an AR-mediated mechanism. To determine a possible mechanism by which AR activation could be influencing [Ca(2+)](i), SERCA2 mRNA levels were measured in primary hippocampal neurons. SERCA2 is inserted into the endoplasmic reticulum (ER) membrane and functions to rapidly pump [Ca(2+)](i) into the ER. Following treatment of primary hippocampal neurons with DHT, SERCA2 mRNA was increased, an effect that was blocked in the presence of flutamide. Taken together these results indicate that DHT, working through AR, causes an up-regulation of SERCA2, which increases the sequestering of [Ca(2+)](i) in the endoplasmic reticulum of hippocampal neurons. Such changes may allow the neurons to respond more robustly to a stimulus and recover more quickly following a highly stimulatory challenge. PMID- 17870251 TI - (Pro-)vitamin D as treatment option for hedgehog-related malignancies. PMID- 17870250 TI - Agrin induced morphological and structural changes in growth cones of cultured hippocampal neurons. AB - The role of agrin in synaptogenesis has been extensively studied. On the other hand, little is known about the function of this extracellular matrix protein during developmental processes that precede the formation of synapses. Recently, agrin was shown to regulate the rate of neurite elongation and the behavior of growth cones in hippocampal and spinal neurons, respectively. However, the molecular mechanisms underlying these effects have not been completely elucidated. In the present study, we analyzed the morphological and molecular changes induced by agrin in growth cones of hippocampal neurons that developed in culture. Morphometric analysis showed a significant enlargement of growth cones of hippocampal neurons cultured in the presence of agrin. These agrin-induced growth cone changes were accompanied by the formation of loops of microtubules highly enriched in acetylated tubulin and an increase in the content of the microtubule-associated protein (MAP)1B. Together, these data provide further insights into the potential molecular mechanisms underlying the effects of agrin on neurite outgrowth in rat central neurons. PMID- 17870252 TI - The Thai HIV/AIDS epidemic at 15 years: sustained needle sharing among southern Thai drug injectors. AB - To explore perceptions and attitudes towards needle sharing among clinic-based injecting drug abusers (IDUs) at a drug-treatment clinic in Hat Yai City, Songkla Province, Southern Thailand. Qualitative methods were used to gather data, including: in-depth interviews with 17 active IDUs and with three nurses, participant observation, review of the IDUs' files, and validation after interview completion to ensure data triangulation. A form of comparative content analysis, including thematic analysis, was used for data analysis. After 15 years of the Thai HIV/AIDS epidemic, most southern Thai IDUs still occasionally engaged in needle sharing although they reported reductions in sharing frequency. Withdrawal symptoms and craving were most commonly cited as compelling reasons to share. Misconceptions about how to determine "healthy" from the "sick" was another key factor underlying sharing. Pooling money for drugs (with subsequent cost-savings) was given priority over purchasing new needles/syringes among disadvantaged IDUs. Receiving HIV voluntary counseling and testing (VCT), however, promotes reduced sharing. Our findings suggest that southern Thai IDUs remain at high risk of acquiring HIV infection, primarily through needle sharing. Harm reduction strategies, such as, providing VCT to all IDUs and promoting needle exchange programs might be beneficial approaches to curbing the rapid spread of HIV. PMID- 17870253 TI - Diverse forms of Pin-II family proteinase inhibitors from Capsicum annuum adversely affect the growth and development of Helicoverpa armigera. AB - Novel forms of Pin-II type proteinase inhibitor (PIs) cDNAs (CanPIs) having three or four inhibitory repeat domains (IRD) were isolated from the developing green fruits of Capsicum annuum. Deduced amino acid (aa) sequences of the CanPIs showed up to 15% sequence divergence among each other or reported inhibitors (CanPI 1AF039398, CanPI-2AF221097). Amino acid sequence analysis of these CanPIs revealed that three IRD PIs have trypsin inhibitory sites, while four IRD CanPIs have both trypsin and chymotrypsin inhibitory sites. Four CanPIs, two having three IRD (CanPI-3AY986465 and CanPI-5DQ005912) and two having four IRD (CanPI 7DQ005913 and CanPI-9DQ005915), were cloned in Pichia pastoris to express recombinant CanPIs. Recombinant CanPIs inhibited 90% of bovine trypsin (TI), while chymotrypsin inhibition (CI) varied with the number of chymotrypsin inhibitory sites in the CanPIs. Recombinant inhibitors inhibited over 70% of the gut proteinase activity of Helicoverpa armigera. H. armigera larvae fed on recombinant CanPIs individually incorporated into artificial diet, showed 35% mortality; in addition, weight gain in H. armigera larvae and pupae was severely reduced compared to controls. Of the four CanPIs, CanPI-7, which has two sites for TI and CI, was the only one to have a consistently antagonistic effect on H. armigera growth and development. We conclude that among the four recombinant PIs tested, CanPIs containing diverse IRDs are best suited for developing insect resistant transgenic plants. PMID- 17870254 TI - Complex life cycles of multicellular eukaryotes: new approaches based on the use of model organisms. AB - A wide variety of life cycles can be found in the different groups of multicellular eukaryotes. Here we provide an overview of this variety, and review some of the theoretical arguments that have been put forward to explain the evolutionary stability of different life cycle strategies. We also describe recent progress in the analysis of the haploid-diploid life cycle of the model angiosperm Arabidopsis thaliana and show how new molecular data are providing a means to test some of the theoretical predictions. Finally, we describe an emerging model organism from the brown algae, Ectocarpus siliculosus, and highlight the potential of this system for the investigation of the mechanisms that regulate complex life cycles. PMID- 17870255 TI - Prevalence of antimicrobial resistance and resistance genes in faecal Escherichia coli isolates recovered from healthy pets. AB - Faecal samples of healthy dogs (n=39) and cats (n=36) obtained in Northern Portugal were seeded on Levine agar plates, and two Escherichia coli isolates per sample were recovered (78 of dogs and 66 of cats). The susceptibility to 16 antimicrobial agents was tested in this series of 144 E. coli isolates. Almost 20% of them showed tetracycline resistance and 12 and 15% presented ampicillin or streptomycin resistance, respectively. The percentage of resistance to the other antimicrobial agents was in all cases below 4%, and no resistant isolates were detected for ceftazidime, imipenem, cefoxitin or amikacin. Two isolates (from one dog) showed cefotaxime-resistance and harboured both the CTX-M-1 and OXA-30 beta lactamases. A bla(TEM) gene was detected in 12 of 17 ampicillin-resistant isolates, the aac(3)-II gene in the three gentamicin-resistant isolates, aadA in 7 of 22 streptomycin-resistant isolates, and tet(A) and/or tet(B) gene in all 28 tetracycline-resistant isolates. The gene encoding class 1 integrase was detected in six E. coli isolates, including the four trimethoprim-sulfamethoxazole resistant isolates and those two harbouring CTX-M-1 and OXA-30 beta-lactamases; different gene cassette arrangements were identified: dfrA1+aadA1 (two isolates), dfrA12+orfF+aadA2 (two isolates) and bla(OXA30)+aadA1 (two isolates). One amino acid change in GyrA protein (Ser83Leu or Asp87Tyr) was detected in four nalidixic acid-resistant and ciprofloxacin-susceptible isolates and two amino acid changes in GyrA (Ser83Leu+Asp87Asn) and one in ParC (Ser80Ile) were identified in one nalidixic acid- and ciprofloxacin-resistant isolate. Faecal E. coli isolates of healthy pets could be a reservoir of antimicrobial resistance genes. PMID- 17870256 TI - Mycobacterium avium subsp. avium distribution studied in a naturally infected hen flock and in the environment by culture, serotyping and IS901 RFLP methods. AB - Mycobacterium avium subsp. avium (MAA) of serotype 2 and genotype IS901+ and IS1245+ was cultured from 21 naturally infected hens (Gallus domesticus) from one smallholder aviary. From a total of 330 samples taken from hens, 124 mycobacteria were detected. Out of which MAA was detected in 103 (35.7%) of 288 tissues, in 4 (19.0%) of 21 swabs of cloacae and in 9 (42.9%) of 21 faeces samples, 8 other conditionally pathogenic mycobacterial species were also isolated. Tuberculous (TB) lesions were found in the liver, spleen and intestinal organs of seven hens. The isolates of MAA (n=58) from 16 infected hens (7 with TB lesions and 9 without TB lesions) were found to be of 3 IS901 RFLP types AE (n=48), AD (n=4) and E (n=6), where these MAA isolates are highly virulent to hens. Mixed infections with IS901 RFLP types (AE and AD) and (AE and E) were also evident in seven hens. From a total of 35 examined environmental samples, 23 mycobacterial isolates were detected. Out of which four (17.4%) MAA isolates of IS901 RFLP type AE and 19 (82.6%) other isolates of conditionally pathogenic mycobacteria were detected. The finding of identical IS901 RFLP types from both tissues and faecal isolates confirms that infected domestic hens are the principal source of infection for other susceptible hosts and lead to the contamination of the surrounding environment. The presence of different IS901 RFLP types in tissue isolates may indicate the repeated incidence of MAA infection and the occurrence of polyclonal infection. PMID- 17870257 TI - Involvement of cholesterol, calcium and progesterone in the induction of capacitation and acrosome reaction of mammalian spermatozoa. AB - The aim of this paper was to review the effects of some important substances involved in the induction of sperm plasma membrane changes referred to as acrosome reaction, namely cholesterol (C), calcium (Ca(2+)) and progesterone (P(4)). For this purpose, mechanisms of capacitation and acrosome reaction (AR) as well as the processes, C, Ca(2+) and P(4) are involved in, are described. Subsequently, to get a better insight into possible beneficial and detrimental effects on sperm function, the occurrence of these molecules in semen extenders is discussed. PMID- 17870258 TI - Pretreatment with phytoestrogen-rich plant decreases breast tumor incidence and exhibits lower profile of mammary ERalpha and ERbeta. AB - OBJECTIVE: Phytoestrogens have been reported to exhibit antiproliferation to human breast cancer cells in vitro. We tested the phytoestrogen-rich, Pueraria mirifica against rat breast cancer induction in vivo. METHODS: The weanling female Spargue-Dawley rats were pretreated with P. mirifica tuberous powder at a dosage of 0, 10, 100 and 1000 mg/kg BW/day for four consecutive weeks. Mammary tumor development was then induced with a single dose of 7,12-DMBA, 80 mg/kg BW, followed by a weekly examination for size and multiplicity of mammary tumors for 20 weeks and finally a necropsy. Mammary tissues were investigated for the virulence of tumor and also monoclonal antibody stained against ERalpha and ERbeta. RESULTS: Pretreatment of 1000 mg/(kgBWday) of P. mirifica tuberous powder resulted in decreasing of the virulence of rat tumor development. The mammary tumor tissues exhibited lower profile of ERalpha and ERbeta as well as ERalpha/ERbeta. CONCLUSION: P. mirifica exhibited prevention of 7,12-DMBA-induced rat mammary tumors, with a proposed mechanism of strong competitive binding of its phytoestrogens to ERalpha and/or synthesis suppressor of ERalpha. PMID- 17870259 TI - Economic impact of Tibolone compared with Continuous-Combined Hormone Replacement Therapy in the management of climacteric symptoms in postmenopausal women. AB - BACKGROUND: Deciding whether to treat postmenopausal women suffering from climacteric symptoms with Continuous Combined Hormone Replacement Therapy (CCHRT) has become increasingly difficult after the release of the Women's Health Initiative results. As a result, development of alternatives to CCHRT is required. Tibolone, which is a synthetic steroid that has estrogenic, progestogenic and androgenic properties, is reported to be a promising alternative. It has been used in Europe, in the same indication as CCHRT, for approximately 20 years but is not yet available in Canada. OBJECTIVE: We carried out a cost-utility analysis comparing a 3-year-treatment course with Tibolone 2.5mg and conjugated equine estrogens (CEE)/medroxyprogesterone acetate (MPA) (0.625 mg/2.5 mg) in the management of postmenopausal women with climacteric symptoms. METHODS: A Markov model, considering persistence, vaginal bleeding and climacteric symptoms, was elaborated to compare the different options in terms of cost and Quality Adjusted Life Years (QALYs), according to a public third-party payer perspective. RESULTS: Compared with CEE/MPA, Tibolone led to an increase in cost (dollars 485 for Tibolone versus dollars 232 for CEE/MPA) and a slight increase in QALYs (2.08 for Tibolone versus 2.05 for CEE/MPA). Consequently, the incremental cost per QALY gained ratio was dollars 9198. CONCLUSION: According to the results, Tibolone seems to be a cost-effective alternative to CEE/MPA. However, those results should be interpreted with caution insofar as the difference in terms of QALY is clinically difficult to value and taking into account the limited data on Tibolone's long-term innocuity. PMID- 17870260 TI - Effects of tibolone and raloxifene on health-related quality of life and sexual function. AB - OBJECTIVES: Study to compare the effects of tibolone and raloxifene on health related quality of life, sexuality and vaginal atrophy. METHODS: A double-blind, randomized study was conducted in 308 osteopenic, but otherwise healthy, postmenopausal women (mean age 66 years) who received tibolone 1.25mg/day or raloxifene 60 mg/day for 2 years. Health-related quality of life was assessed by the women's health questionnaire (WHQ), sexual function by the McCoy female sexuality questionnaire (MFSQ) and vaginal atrophy by assessing the karyopycnotic index (KI) and vaginal maturation (VM). RESULTS: At week 104, the tibolone group showed a trend towards an improved health-related quality of life (HRQoL) mean score in eight out of nine WHQ domains. HRQoL scores approximated values for premenopausal women, being pre-defined as "clinically relevant". The raloxifene group showed a trend to a diminished HRQoL mean score from baseline to week 104. No difference could be assessed between the tibolone and raloxifene group in mean total score and separate domains' scores of the MFSQ, except for the vaginal lubrication domain (p=0.037). The increase in KI and VM was statistically significantly greater with tibolone than with raloxifene (for both KI and VM p<0.0001). Tibolone and raloxifene were equally well tolerated. CONCLUSIONS: In older postmenopausal women, tibolone treatment showed a trend towards an improvement in quality of life and sexuality when compared to raloxifene. PMID- 17870261 TI - Preparation and characterization of sodium ferulate entrapped bovine serum albumin nanoparticles for liver targeting. AB - Sodium ferulate (SF) loaded nanoparticles were prepared by desolvation procedure and subsequent cross-linking of the wall material of bovine serum albumin (BSA). Several factors in the nanoencapsulation process, such as the addition rate of the desolvation agent, composition of BSA and SF solution, amount of the cross linker glutaraldehyde, were investigated to elucidate their influences on the particle size, zeta potential, drug loading and encapsulation efficiency of the resulted nanoparticles. The obtained spherical nanoparticles were negative charged with zeta potential from -20 to -40 mV, and characterized between 100 and 200 nm with a narrow size distribution. In the condition of introducing 1.0 mL 8% glutareldehyde per mg of BSA, the drug entrapment efficiency (EE) of 80% (w/w) and loading capacity of about 16% (w/w) could be achieved for the cross-linked BSA nanoparticles with SF encapsulated (SF-BSA-NP). And the drug EE was decreased along with the increasing amount of glutareldehyde used for cross-linking. The in vitro drug release properties of SF-BSA-NP behaved with an initial burst effect and then sustained-release stage. To some extent, the drug release rate could be adjusted by cross-linking with different amount of glutaraldehyde. Compared with SF solution, SF-BSA-NP showed a much higher drug distribution into liver and a lower drug concentration in other tissues, after intravenously injected to mice. So, BSA based nanoparticles might be a suitable controlled released carrier for the freely water-soluble drug SF and further hepatic targeted drug delivery. PMID- 17870262 TI - Probing the permeation enhancement of mefenamic acid by ethanol across full thickness skin, heat-separated epidermal membrane and heat-separated dermal membrane. AB - The permeation enhancement of mefenamic acid by ethanol across full-thickness porcine skin, heat-separated epidermal membrane and heat-separated dermal membrane has been probed. Three donor phases saturated with mefenamic acid were used: (1) PEG400; (2) PEG400 with 10% ethanol; (3) mefenamic acid in PEG 400 with 30 mg ml(-1) cetrimide; these were applied to membranes mounted in Franz diffusion-type cells with 30 mg ml(-1) cetrimide as receptor phase (n > or =5). Across full-thickness skin, the flux was below the limit of detection from PEG400, but with the inclusion of 10% ethanol was 0.83 microg cm(-2)h(-1). When cetrimide was present in the donor (and receptor) phase the flux was very low 0.1 microg cm(-2)h(-1). Across heat-separated epidermal membrane the flux from PEG was 11.9+/-2.4 microg cm(-2)h(-1) with a 2.42 x increase in flux observed when 10% ethanol was present (p=0.0095). Across heat-separated dermal membrane the flux from PEG400 was 0.62+/-0.13 microg cm(-2)h(-1), with a 2.34 x increase in flux observed when 10% ethanol was present (p=0.0027). To conclude, complexation and co-permeation with ethanol via a pull effect was confirmed as the mechanism of enhanced skin permeation of mefenamic acid. Full thickness skin provides a more effective barrier than either isolated dermis or epidermis, casting doubt over the use of heat-separated epidermal membranes to model skin permeation and penetration. There was evidence that cetrimide does not cause skin barrier modulation, supporting its use as an effective receptor phase. PMID- 17870263 TI - Traditional dietary additives of the Maasai are antiviral against the measles virus. AB - Although ethnopharmacological investigations emphasize the importance of medicinal plants in developing countries, species used regularly with diet are under-investigated and potentially make greater contributions to health. Thirteen traditional plants most commonly added to milk/soups by the Maasai for perceived health benefits were tested for activity against measles virus (MV) using non medicinal plants as controls. Antiviral effects of plant extracts were sought using a modified neutralization assay. Methanolic extracts of medicinal species exhibited significantly greater activity neutralizing MV in vitro in comparison to non-medicinal extracts (p<0.02). Four of 13 (31%) medicinal species versus 0/13 controls had measurable effects against MV in vitro. Olinia rochetiana (Olkirenyi) and Warburgia ugandensis (Osokonoi) extracts were most potent with the number of plaque forming units reduced 37- and 34-fold, respectively. Given the importance of monocytes in the dissemination of MV, we assessed the capacity of a subset of plant extracts to inhibit MV growth in monocytoid cell line, U937. MV output from U937 cells was significantly reduced by four of seven medicinal plant extracts (mean reduction 48 h: 39.0+/-26.0%, range 3.5-87%; 72 h: 56.4+/ 29.5%, range 14.1-103.1%) (p<0.05). This study provides evidence that medicinal plants added to the Maasai diet may contribute to the modulation of viral infections. PMID- 17870264 TI - Hepatoprotective activity of Phyllanthus amarus Schum. et. Thonn. extract in ethanol treated rats: in vitro and in vivo studies. AB - The present study was undertaken to investigate the protective effect and possible mechanism of aqueous extract from Phyllanthus amarus Schum. et. Thonn. (PA) on ethanol-induced rat hepatic injury. In the in vitro study, PA (1-4 mg/ml) increased %MTT reduction assay and decreased the release of transaminases (AST and ALT) in rat primary cultured hepatocytes being treated with ethanol. Hepatotoxic parameters studied in vivo included serum transaminases (AST and ALT), serum triglyceride (STG), hepatic triglyceride (HTG), tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta), together with histopathological examination. In acute toxicity study, single dose of PA (25, 50 and 75 mg/kg, p.o.) or SL (silymarin, a reference hepatoprotective agent, 5 mg/kg), 24h before ethanol (5 g/kg, p.o.) lowered the ethanol-induced levels of transaminases (AST and/or ALT). The 75 mg/kg PA dose gave the best result similar to SL. Treatment of rats with PA (75 mg/(kg day), p.o.) or SL (5 g/(kg day), p.o.) for 7 days after 21 days with ethanol (4 g/(kg day), p.o.) enhanced liver cell recovery by bringing the levels of AST, ALT, HTG and TNF-alpha back to normal. Histopathological observations confirmed the beneficial roles of PA and SL against ethanol-induced liver injury in rats. Possible mechanism may involve their antioxidant activity. PMID- 17870265 TI - A case of syryngocystadenoma papilliferum (SCAP) involving middle ear, presenting with otomastoiditis and cerebral abscess. AB - Syryngocystadenoma papilliferum (SCAP) is an uncommon cutaneous adnexal neoplasm of apocrine gland origin. Until now, fewer than 200 cases have been reported in international literature, of which 12 cases involved the external ear. No cases of SCAP involving the middle ear have been reported. We describe a case of SCAP of external and middle ear, presenting with otomastoiditis and cerebral abscess; this aggressive behavior, never reported for a benign adenoma of the external or middle ear, could lead to a differential diagnosis with cholesteatoma or malignancies. PMID- 17870266 TI - Comparison of hypothalamopituitary axis dysfunction of intrasellar and third ventricular craniopharyngiomas in children. AB - In this study, we attempted to determine if different locations of a tumor influence the hypothalamopituitary axis function and outcomes with childhood craniopharyngiomas. The preoperative, postoperative, and long-term follow-up endocrinological disturbances of 66 children with a craniopharyngioma were retrospectively studied. The patients were divided into two subgroups according to the location of the tumor (intrasellar and third ventricle floor). The mean age at onset was 8.02 (range, 1.42-17.58)years. These patients were followed-up for a median duration of 7.2 (range, 2-22)years. Vision problems as the first symptom were more common in Group One (with intrasellar tumors) compared to Group Two (55.6% vs 15.4%; p=0.001; Fisher's exact test). Increased intracranial pressure was the most common initial symptom in patients in Group Two (51.3%) and the second most common symptom in Group One (37%). The majority of patients in both Group One and Group Two required some forms of pituitary hormone supplements (96% vs 84%). At the last follow-up, more patients with intrasellar craniopharyngiomas needed cortisone supplements (79.2% in Group One vs 45.9% in Group Two; p=0.016; Fisher's exact test); however, children with third ventricle floor tumors had more prevalent weight gain (4.2% in Group One vs 27.0% in Group Two; p=0.038; Fisher's exact test). There were different initial presentations and endocrinological outcomes between children with intrasellar and third ventricle floor craniopharyngiomas. The intrasellar tumors had greater pituitary hormone disturbance. However, at the long-term follow-up, children with third ventricle floor tumors had a greater prevalence of being overweight and obese, which was associated with hypothalamic dysfunction. PMID- 17870267 TI - Mental retardation, spasticity, basal ganglia calcification, cerebral white matter lesions, multiple endocrine defects, telangiectasia and atrophic skin: a new syndrome? AB - We report on an 8-year-old boy with mental retardation and spastic tetraparesis associated with atrophic skin on the face and extremities, telangiectasia, and severe dental caries. Basal ganglia calcification and multiple lesions in the subcortical white matter have been present since infancy. The patient has complications of liver dysfunction, multiple endocrine defects, and elevation of blood/cerebrospinal fluid lactate. Extensive laboratory examinations, including skin and muscle biopsies, and UV- and mitomycin C-sensitivity tests on fibroblasts, provided no evidence of a specific disease entity. No deterioration was noted, and supplementation of riboflavin and other vitamins had no apparent effect on the neurodevelopmental status of this patient. This patient may represent a novel disease entity, with unclear pathogenesis. PMID- 17870268 TI - [Effectiveness of triennial anti-influenza vaccination in French military during the 2003-2004 influenza season]. AB - BACKGROUND: Influenza may rapidly disseminate within populations living in confined settings, causing considerable morbidity and disrupting daily activities. The French military health-care system set up since 1994 a prevention strategy based on triennial anti-influenza vaccination. The aim of this study was to evaluate the effectiveness of this strategy during the 2003-2004 influenza season. METHODS: We conducted a matched case-control study from 10/01/2003 through 3/31/2004. Cases were laboratory-confirmed influenza cases. The controls were not to have presented influenza during all the period of study. Controls were matched to cases by sex, army unit and age. Subgroups were categorized into four groups by vaccination regimen [0-1 year], [1-2 years], [2-3 years], [3 years and more or unvaccinated]. RESULTS: One hundred and eighteen cases and 435 controls were included. The proportion of correctly vaccinated subjects (100% was found for the high field strength elements (Hf, Th, Zr, Nb). The rare earth element (REE) concentrations, which vary over 3 orders of magnitude, have %RSD(r) and %RSD(R) values at 8-15% and 20-32%, respectively. However, the REE patterns (which are very important for paleo-environmental, taphonomic and paleo-oceanographic analyses) are much more consistent. These data suggest that the complex and unpredictable nature of the mineralogical and chemical composition of fossil bone makes it difficult to set-up and calibrate analytical instruments using conventional standards, and may result in non-spectral matrix effects. We propose an analytical protocol that can be employed in future inter-laboratory studies to produce a certified fossil bone geochemical standard. PMID- 17870282 TI - The application and comparison of several chemometric methods of excitation emission matrix spectra in studying the interactions of metal complexes with DNA. AB - The interactions of fs DNA and two metal complexes [Cu(phen)SO4] x 2 H2O and [Ni(phen)SO4] x 2 H2O were explored by several chemometric methods, including parallel factor (PARAFAC), singular value decomposition-least squares (SVD-LS), and singular value decomposition-nonnegative least squares (SVD-NNLS) of excitation-emission matrix spectra (EEMs). The applications of SVD-LS and SVD NNLS in this domain have been discussed. Rayleigh scatter part is avoided by ordered zero and reconstructed by linear interpolation. The importance of avoiding Rayleigh scatter has also been discussed. All the three methods do well in qualitative analysis. SVD-LS does best in present small changes of ethidium bromide (EB). In order to get accurate results, PARAFAC and SVD-NNLS can be utilized together in quantitative analysis. All the three chemometric methods indicate that the DNA binding modes of [Cu(phen)SO4] x 2 H2O are hydrogen bond effect and intercalation, while intercalation is the only DNA binding mode for [Ni(phen)SO4] x 2 H2O. These results are verified by the electronic absorption and emission fluorescence spectra. Just like PARAFAC, both SVD-LS and SVD-NNLS are proven to be convenient and convincing in studying the interactions between nucleic acids and complexes. PMID- 17870283 TI - Simultaneous determination of iron and aluminium by differential kinetic spectrophotometric method and chemometrics. AB - A differential kinetic spectrophotometric method was researched and developed for the simultaneous determination of iron and aluminium in food samples. It was based on the direct reaction kinetics and spectrophotometry of these two metal ions with Chrome Azurol S (CAS) in ethylenediamine-hydrochloric acid buffer (pH 6.3). The results were interpreted with the use of chemometrics. The kinetic runs and the visible spectra of the complex formation reaction were studied between 540 and 750 nm every 30 s over a total period of 285 s. A set of synthetic metal mixture samples was used to build calibrations models. These were based on the spectral and kinetic two-way data matrices, which were processed separately by the radial basis function-artificial neural network (global RBF-ANN) method. The prediction performance of these models was poorer than that from the combined kinetic-spectral three-way array, which was similarly processed by the same method (% relative prediction error (RPE(T))=5.6). These results demonstrate that improved predictions can be obtained from the data array, which has more information, and that appropriate chemometrics methods can enhance analytical performance of simple techniques such as spectrophotometry. Other chemometrics models were then applied: N-way partial least squares (NPLS), parallel factor analysis (PARAFAC), back propagation-artificial neural network (BP-ANN), single radial basis function-artificial neural network (RBF-ANN), and principal component neural network (PC-RBF-ANN). There was no substantial difference between the methods with the overall %RPE(T) range being 5.0-5.8. These two values corresponded to the NPLS and BP-ANN models, respectively. The proposed method was applied for the determination of iron and aluminium in some commercial food samples with satisfactory results. PMID- 17870284 TI - Bootstrap classification and point-based feature selection from age-staged mouse cerebellum tissues of matrix assisted laser desorption/ionization mass spectra using a fuzzy rule-building expert system. AB - A bootstrap method for point-based detection of candidate biomarker peaks has been developed from pattern classifiers. Point-based detection methods are advantageous in comparison to peak-based methods. Peak determination and selection are problematic when spectral peaks are not baseline resolved or on a varying baseline. The benefit of point-based detection is that peaks can be globally determined from the characteristic features of the entire data set (i.e., subsets of candidate points) as opposed to the traditional method of selecting peaks from individual spectra and then combining the peak list into a data set. The point-based method is demonstrated to be more effective and efficient using a synthetic data set when compared to using Mahalanobis distance for feature selection. In addition, probabilities that characterize the uniqueness of the peaks are determined. This method was applied for detecting peaks that characterize age-specific patterns of protein expression of developing and adult mouse cerebella from matrix assisted laser desorption/ionization (MALDI) mass spectrometry (MS) data. The mice comprised three age groups: 42 adults, 19 14-day-old pups, and 16 7-day-old pups. Three sequential spectra were obtained from each tissue section to yield 126, 57 and 48 spectra for adult, 14 day-old pup, and 7-day-old pup spectra, respectively. Each spectrum comprised 71,879 mass measurements in a range of 3.5-50 kDa. A previous study revealed that 846 unique peaks were detected that were consistent for 50% of the mice in each age group (C. Laurent, D.F. Levinson, S.A. Schwartz, P.B. Harrington, S.P. Markey, R.M. Caprioli, P. Levitt, Direct profiling of the cerebellum by MALDI MS: a methodological study in postnatal and adult mouse, J. Neurosci. Res. 81 (2005) 613-621.). A fuzzy rule-building expert system (FuRES) was applied to investigate the correlation of age with features in the MS data. FuRES detected two outlier pup-14 spectra. Prediction was evaluated using 100 bootstrap samples of 2 Latin partitions (i.e., 50:50 split between training and prediction set) of the mice. The spectra without the outliers yielded classification rates of 99.1+/-0.1%, 90.1+/-0.8%, and 97.0+/-0.6% for adults, 14-day-old pups, and 7-day-old pups, respectively. At a 95% level of significance, 100 bootstrap samples disclosed 35 adult and 21 pup distinguishing peaks for separating adults from pups; and 8 14 day-old and 15 7-day-old predictive peaks for separating 14-day-old pup from 7 day-old pup spectra. A compressed matrix comprising 40,393 points that were outside the 95% confidence intervals of one of the two FuRES discriminants was evaluated and the classification improved significantly for all classes. When peaks that satisfied a quality criterion were integrated, the 55 integrated peak areas furnished significantly improved classification for all classes: the selected peak areas furnished classification rates of 100%, 97.3+/-0.6%, and 97.4+/-0.3% for adult, 14-day-old pups, and 7-day-old pups using 100 bootstrap Latin partitions evaluations with the predictions averaged. When the bootstrap size was increased to 1000 samples, the results were not significantly affected. The FuRES predictions were consistent with those obtained by discriminant partial least squares (DPLS) classifications. PMID- 17870285 TI - Use of different artificial neural networks to resolve binary blends of monocultivar Italian olive oils. AB - The problem of authenticating extra virgin olive oil varieties is particularly important from the standpoint of quality control. After having shown in our previous works the possibility of discriminating oils from a single variety using chemometrics, in this study a combination of two different neural networks architectures was employed for the resolution of simulated binary blends of oils from different cultivars. In particular, a Kohonen self-organizing map was used to select the samples to include in the training, test and validation sets, needed to operate the successive calibration stage, which has been carried out by means of several multilayer feed-forward neural networks. The optimal model resulted in a validation Q2 in the range 0.91-0.96 (10 data sets), corresponding to an average prediction error of about 5-7.5%, which appeared significantly better than in the case of random or Kennard-Stone selection. PMID- 17870286 TI - Spectrophotometric investigation of the effect of beta-cyclodextrin on the intramolecular cyclization reaction of catecholamines using rank annihilation factor analysis. AB - The catalytic effect of beta-cyclodextrin (beta-CD) on the intramolecular cyclization reaction of catecholamines dopamine, methyldopa and levodopa after their oxidation with periodate was investigated spectrophotometrically using rank annihilation factor analysis (RAFA). The method was based on the effect of beta CD concentration on the intramolecular cyclization reaction of the investigated catecholamines after their oxidation with potassium periodate. In order to perform RAFA, concentration profiles were calculated by optimizing the value of formation constant. The rank of original data matrix can be reduced by one by annihilating the information of the cyclization reaction in the absence of beta CD. The rate constant for the reactions in the presence and absence of beta-CD was also determined. The best estimation of rate constant in the presence of beta CD reduces the rank of the system to zero (noise level). The method was evaluated using synthetic data as well as experimental data and good results were obtained. PMID- 17870287 TI - Anodic stripping voltammetry at a new type of disposable bismuth-plated carbon paste mini-electrodes. AB - A new type of disposable carbon paste mini-electrodes (CPmEs), with dimensions in the 50-300 microm range, have been fabricated by heat-shrinking the end-tip of plastic micropipette tips and filling them with carbon paste. The CPmEs have been characterized by microscopic and electrochemical means and tested as substrates for in situ plated Bi film electrodes (BiF-CPmEs), used in the determination of heavy metals by square wave anodic stripping voltammetry (SWASV). It was found that this new class of CPmEs combines the advantages of carbon paste electrodes (readily renewable surface and high surface area) with those of near microelectrode behaviour (no stirring or electrolyte excess needed). During SWASV experiments in unstirred Pb(II) and Cd(II) solutions well-shaped stripping peaks were obtained whose height varied linearly with analyte concentration in the wide 1x10(-8) to 10(-6) M range, both in acetate buffer and unbuffered solutions. Under optimal conditions detection limits of 8x10(-10) and 1.3x10(-9) M were achieved for Pb(II) and Cd(II), respectively and in a trial application, these metal ions have been determined in a spiked tap water sample using a BiF-CPmE. PMID- 17870288 TI - Purity of potassium hydrogen phthalate, determination with precision coulometric and volumetric titration--a comparison. AB - The mass fraction of potassium hydrogen phthalate (KHP) from a specific batch was certified as an acidimetric standard. Two different analytical methods on a metrological level were used to carry out certification analysis: precision constant current coulometric and volumetric titration with NaOH. It could be shown that with a commercial automatic titration system in combination with a reliable software for the end-point detection it is possible to produce equivalent results with the same accuracy in comparison to a definite method handled by a fundamental apparatus for traceable precision coulometry. Prerequisite for titrations are that a high number of single measurement are applied which are calibrated with a high precision certified reference material. PMID- 17870289 TI - Assessment of elemental mobility in soil using a fluidised bed approach with on line ICP-MS analysis. AB - A new method has been developed to analyse the mobility of elements within soils employing counter-current flow soil contacting in a fluidised bed (FB) column. This method alleviates the problem of irreproducible peaks suffered by state-of the-art micro-column techniques as a result of particle compaction. Reproducible extraction profiles are produced through the leaching of soil with a linear gradient of 0.05 mol L(-1) ammonium sulphate to 0.11 mol L(-1) acetic acid using a high pressure liquid chromatography (HPLC) quaternary pump, and the continuous monitoring of the elements in the leachate with inductively coupled plasma mass spectrometry (ICP-MS). Quantification of the procedure is achieved with an external flow injection (FI) calibration method. Flow rate and FB column length were investigated as critical parameters to the efficiency of the extraction methodology. It was found that an increase in the column length from 10 to 20 cm using a flow rate of 0.15 mL min(-1) produced the same increase in extracted elemental concentration as an increase in flow rate from 0.15 to 0.30 mL min(-1). In both examples, the increase in the concentration of elements leached from the soil may be ascribed to the increase in the concentration gradient between the solid and liquid. The exhaustive nature of the technique defines the maximum leachable concentration within the operationally defined leaching parameters of the exchangeable phase, providing a more accurate assessment of the risk associated with the elements in the soil for the phase providing the greatest risk to the environment. The multi-elemental high sensitivity nature of the on line detector provides an accurate determination of the associations present between the elements in the soil, and the identification of multiple phases within the exchangeable phase through the presence of multiple peaks in the extraction profiles. It is possible through the deconvolution of these extraction profiles that the concentration corresponding to the peaks identified can be defined. PMID- 17870290 TI - Study on the resonance Rayleigh scattering spectra of the interactions of palladium (II)-cephalosporins chelates with 4,5-dibromofluorescein and their analytical applications. AB - In pH 2.8-3.8 BR buffer medium, the third generation cephalosporin antibiotics (TGCs) such as ceftazidime (CZD), ceftriaxone (CTRX), cefoperazone (CPZ), and cefotaxime (CFTM) react with palladium(II) (Pd(II)) to form 1:2 yellowish-brown cationic chelates, which further react with 4,5-dibromofluorescein (DBF) to form 1:3 brown ion-association complexes. As a result, not only the spectra of absorption and fluorescence are changed, but also the resonance Rayleigh scattering (RRS) is enhanced greatly and the new RRS spectra are observed. The four TGCs products have similar spectral characteristics and their maximum RRS wavelengths are all located at 291 nm. The quantitative determination ranges and the detection limits of the four TGCs are 0.0065-1.0 microg mL(-1) and 2.0 ng mL( 1) for CZD, 0.0070-1.1 microg mL(-1) and 2.2 ng mL(-1) for CTRX, 0.0090-1.6 microg mL(-1) and 2.7 ng mL(-1) for CPZ, and 0.014-2.2 microg mL(-1) and 4.2 ng mL(-1) for CFTM, respectively. The optimum conditions of the reactions and the effects of foreign substances are investigated, and the composition of ion association complexes is discussed also. Based on the ion-association reaction, a highly sensitive, simple and rapid method has been proposed to the determination of TGCs. PMID- 17870291 TI - Light scattering sensing detection of pathogens based on the molecular recognition of immunoglobulin with cell wall-associated protein A. AB - In this contribution, we report a rapid optical detection method of pathogens using Staphylococcus aureus (S. aureus) as the model analyte based on the molecular recognition of immunoglobulin with cell wall-associated Protein A (SpA). It was found that the molecular recognition of human immunoglobulin (IgG) with protein A on the cell wall of S. aureus on glass slide sensing area could result in strong surface enhanced light scattering (SELS) signals, and the SELS intensity (deltaI) increases proportionally with the concentration of S. aureus over the range of 2.5x10(5)-1.0x10(8) CFU mL(-1) with right angle light scattering (RALS) signals detection mode. In order to identify the solid support based molecular recognition between IgG with SpA, we also employed water-soluble CdS quantum dots (CdS-QDs) as a fluorescent marker for IgG by immobilizing the IgG onto the surfaces of CdS-QDs through covalent binding in order to generate recognition probes for SpA on the cell wall of S. aureus. Consequently, the fluorescent method also showed that the detection for pathogens with solid supports is reliable based on the molecular recognition of IgG with SpA. PMID- 17870292 TI - Catalytic activity of iron hexacyanoosmate(II) towards hydrogen peroxide and nicotinamide adenine dinucleotide and its use in amperometric biosensors. AB - Hydrogen peroxide and nicotinamide adenine dinucleotide (NADH) may be determined amperometrically using screen-printed electrodes chemically modified with iron(III) hexacyanoosmate(II) (Osmium purple) in flow injection analysis (FIA). The determination is based on the exploitation of catalytic currents resulting from the oxidation/reduction of the modifier. The performance of the sensor was characterized and optimized by controlling several operational parameters (applied potential, pH and flow rate of the phosphate buffer). Comparison has been made with analogous complexes of ruthenium (Ruthenium purple) and iron (Prussian blue). Taking into account the sensitivity and stability of corresponding sensors, the best results were obtained with the use of Osmium purple. The sensor exhibited a linear increase of the amperometric signal with the concentration of hydrogen peroxide in the range of 0.1-100 mg L(-1) with a detection limit (evaluated as 3sigma) of 0.024 mg L(-1) with a R.S.D. 1.5% for 10 mg L(-1) H2O2 under optimized flow rate of 0.4 mL min(-1) in 0.1M phosphate buffer carrier (pH 6) and a working potential of +0.15 V versus Ag/AgCl. Afterwards, a biological recognition element--either glucose oxidase or ethanol dehydrogenase--was incorporated to achieve a sensor facilitating the determination of glucose or ethanol, respectively. The glucose sensor gave linearity between current and concentration in the range from 1 to 250 mg L(-1) with a R.S.D. 2.4% for 100 mg L(-1) glucose, detection limit 0.02 mg L(-1) (3sigma) and retained its original activity after 3 weeks when stored at 6 degrees C. Optimal parameters in the determination of ethanol were selected as: applied potential +0.45 V versus Ag/AgCl, flow rate 0.2 mL min(-1) in 0.1 M phosphate buffer carrier (pH 7). Different structural designs of the ethanol sensor were tested and linearity obtained was up to 1000 mg L(-1) with a maximum R.S.D. of 5.1%. Applications in food analysis were also examined. PMID- 17870293 TI - A stoichiometric imprinted chelating resin for selective recognition of copper(II) ions in aqueous media. AB - This work reports the preparation of a new copper(II) ion-imprinted polymer (IIP) material, using 5,6;14,15-dibenzo-1,4-dioxa-8,12-diazacyclopentadecane-5,14-diene (DBDA15C4) and 2-vinylpyridine (VP) as a non-vinylated chelating agent and a functional vinyl monomer, respectively. The Cu2+ ion can form stable complexes with DBDA15C4 and VP. The stoichiometries of Cu2+-DBDA15C4 and ternary Cu2+ DBDA15C4-VP complexes were elucidated using conductometric and spectrophotometric methods, and found to be Cu2+ (DBDA15C4), Cu2+ (DBDA15C4)2 and Cu2+ (DBDA15C4)(VP)2. The results obtained from solution studies were also supported by ab initio theoretical calculations. The resulting ternary complex Cu2+ (DBDA15C4)(VP)2 was copolymerized with ethyleneglycoldimethacrylate, as a cross linking monomer, via bulk polymerization method. The imprinted copper ion was removed from the polymeric matrix by 0.1 M HNO3. The Cu2+-imprinted polymer particles were characterized by IR spectroscopy and elemental analysis. Optimum pH range for rebinding of Cu2+ on the IIP and equilibrium binding time were 7.0 7.5 and 45 min, respectively. Sorbent capacity and enrichment factor for Cu2+ were obtained as 75.3+/-1.9 micromol g(-1) and 100, respectively. In selectivity study, it was found that imprinting results in increased affinity of the material toward Cu2+ ion over other competitor metal ions with the same charge and close ionic radius. The prepared IIPs were repeatedly used and regenerated for five times without a significant decrease in polymer binding affinities. PMID- 17870294 TI - Validated stability-indicating densitometric thin-layer chromatography: application to stress degradation studies of minocycline. AB - A simple, stability-indicating high-performance thin-layer liquid chromatographic (HPTLC) method for analysis of minocycline was developed and validated. The densitometric analysis was carried out at 345 nm using methanol-acetonitrile isopropyl alcohol-water (5:4:0.5:0.5, v/v/v/v) as mobile phase. The method employed TLC aluminium plates pre-coated with silica gel 60F-254 as the stationary phase. To achieve good result, plates were sprayed with a 10% (w/v) solution of disodium ethylene diaminetetraacetic acid (EDTA), the pH of which was adjusted to 9.0. Compact spots of minocycline were found at R(f) = 0.30+/-0.02. For proposed procedure, linearity (r = 0.9997), limit of detection (3.7 ng spot( 1)), recovery (99.23-100.16%), and precision (% R.S.D. < or = 0.364) was found to be satisfactory. The drug undergoes acidic and basic degradation, oxidation and photodegradation. All the peaks of degradation products were well resolved from the pure drug with significantly different R(f) values. The acidic and alkaline degradation kinetics of minocycline, evaluated using this method, is found to be of first order. PMID- 17870295 TI - Electrophoresis mobility shift assay and biosensor used in studying the interaction between bleomycin A5 and DNA. AB - DNA is the potential target of numerous drugs utilized widely in clinical cancer therapy. Here we employed bleomycin A5, with its deactivated form as contrast, to investigate the interaction between small pharmaceutical and DNA. Electrophoresis mobility shift assay (EMSA) which is a common technique used in studying specific interactions between DNA and proteins is applied in visualizing the binding of bleomycin A5 with DNA intuitively. More accurate association equilibrium constant for native and deactivated bleomycin A5 to DNA achieved on biosensor IAsys AUTO+ is 1.25x10(4) and 1.3x10(3) M(-1), respectively. With combination of EMSA and biosensor, a qualitative and quantitative method is described, which can be extended to studying the binding of most small molecules with targeting DNA and serves as a powerful tool in designing and screening for novel drugs. PMID- 17870296 TI - Iron-chelating agents never suppress Fenton reaction but participate in quenching spin-trapped radicals. AB - Hydroxyl radical formation by Fenton reaction in the presence of an iron chelating agent such as EDTA was traced by two different assay methods; an electron spin resonance (ESR) spin-trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), and high Performance liquid chromatography (HPLC)-fluorescence detection with terephthalic acid (TPA), a fluorescent probe for hydroxyl radicals. From the ESR spin-trapping measurement, it was observed that EDTA seemed to suppress hydroxyl radical formation with the increase of its concentration. On the other hand, hydroxyl radical formation by Fenton reaction was not affected by EDTA monitored by HPLC assay. Similar inconsistent effects of other iron-chelating agents such as nitrylotriacetic acid (NTA), diethylenetriamine penta acetic acid (DTPA), oxalate and citrate were also observed. On the addition of EDTA solution to the reaction mixture 10 min after the Fenton reaction started, when hydroxyl radical formation should have almost ceased but the ESR signal of DMPO-OH radicals could be detected, it was observed that the DMPO-OH* signal disappeared rapidly. With the simultaneous addition of Fe(II) solution and EDTA after the Fenton reaction ceased, the DMPO-OH* signal disappeared more rapidly. The results indicated that these chelating agents should enhance the quenching of [DMPO-OH]* radicals by Fe(II), but they did not suppress Fenton reaction by forming chelates with iron ions. PMID- 17870297 TI - CAMP factor is not essential for systemic virulence of Group B Streptococcus. AB - The Gram-positive pathogen Group B Streptococcus (GBS) is the leading cause of bacterial pneumonia, sepsis, and meningitis in human newborns. GBS elaborates a pore-forming toxin known as CAMP factor that synergizes with Staphylococcus aureus beta-toxin, generating a co-hemolytic reaction useful in identification of GBS in the clinical laboratory. To evaluate the indirect evidence implicating CAMP factor in GBS pathogenesis, the cfb gene encoding the pore-forming cytotoxin was deleted by precise allelic replacement. The virulence properties of the CAMP factor mutant were then explored by a series of in vitro and in vivo assays. Compared to wild-type, the isogenic GBS Deltacfb mutant demonstrated equivalent phagocyte resistance and endothelial cell invasiveness and also retained full virulence in a mouse model of infection. Our data suggest that CAMP factor expressed in its native context is not essential for systemic virulence of GBS. PMID- 17870298 TI - SIV infection decreases sympathetic innervation of primate lymph nodes: the role of neurotrophins. AB - The sympathetic nervous system regulates immune responses in part through direct innervation of lymphoid organs. Recent data indicate that viral infections can alter the structure of lymph node innervation. To determine the molecular mechanisms underlying sympathetic denervation during Simian Immunodeficiency Virus (SIV) infection, we assessed the expression of neurotrophic factors and neuromodulatory cytokines within lymph nodes from experimentally infected rhesus macaques. Transcription of nerve growth factor (NGF), brain-derived neurotropic factor (BDNF) and neurotrophin-4 (NT4) decreased significantly in vivo during chronic SIV infection, whereas expression of the neuro-inhibitory cytokine interferon-gamma (IFN gamma) was up-regulated. Acute SIV infection of macaque leukocytes in vitro induced similar changes in the expression of neurotrophic and neuro-inhibitory factors, indicative of an innate immune response. Statistical mediation analyses of data from in vivo lymph node gene expression suggested that coordinated changes in expression of multiple neuromodulatory factors may contribute to SIV-induced depletion of catecholaminergic varicosities within lymphoid tissue. Given previous evidence that lymph node catecholaminergic varicosities can enhance SIV replication in vivo, these results are consistent with the hypothesis that reduced expression of neurotrophic factors during infection could constitute a neurobiological component of the innate immune response to viral infection. PMID- 17870412 TI - Death, adaptation and regulation: the three pillars of immune tolerance restrict the risk of autoimmune disease caused by molecular mimicry. AB - Extensive cross-reactivity in T cell receptor (TCR) recognition of peptide-MHC (pMHC) complexes seems to be essential to give sufficient immune surveillance against invading pathogens. This carries with it an inherent risk that T cells activated during a response to clear an infection can, perhaps years later, respond to a self pMHC of sufficient similarity. This lies at the heart of the molecular mimicry theory. Here we discuss our studies on the disease-causing potential of altered peptide ligands (APL) based on the sequence of a single autoantigenic epitope, the Ac1-9 peptide of myelin basic protein that induces experimental autoimmune encephalomyelitis in mice. These show that the window of similarity to self for induction of disease by cross-reactive non-self peptides is actually quite restricted. We show that each of the three pillars of immune tolerance (death, anergy/adaptation and regulation) has a role in limiting the risk of molecular mimicry by maintaining a threshold for harm. PMID- 17870413 TI - Predictability analysis of absence seizures with permutation entropy. AB - In this study, we investigate permutation entropy as a tool to predict the absence seizures of genetic absence epilepsy rats from Strasbourg (GAERS) by using EEG recordings. The results show that permutation entropy can track the dynamical changes of EEG data, so as to describe transient dynamics prior to the absence seizures. Experiments demonstrate that permutation entropy can successfully detect pre-seizure state in 169 out of 314 seizures from 28 rats and the average anticipation time of permutation entropy is around 4.9s. These findings could shed new light on the mechanism of absence seizure. In comparison with results of sample entropy, permutation entropy is better able to predict absence seizures. PMID- 17870414 TI - ATX-S10(Na)-photodynamic therapy inhibits cytokine secretion and proliferation of lymphocytes. PMID- 17870415 TI - Evidence supporting antioxidant action of adipose-derived stem cells: protection of human dermal fibroblasts from oxidative stress. AB - BACKGROUND: Mesenchymal stem cells within the stromal-vascular fraction of subcutaneous adipose tissue, adipose-derived stem cells (ADSCs), produced soluble factors and they exhibit diverse pharmacological effects in skin biology. OBJECTIVE: The present study examines the protective effect of ADSCs for human dermal fibroblasts (HDFs) through anti-oxidation in a tert-butyl hydroperoxide (tbOOH) induced oxidative injury model. METHODS AND RESULTS: The conditioned medium of ADSCs (ADSC-CM) was harvested and tested for antioxidant action. ADSC CM had an antioxidant effect as potent as 100 microM ascorbic acid and various antioxidant proteins were detected in ADSC-CM by proteomic analysis. Morphological change and cell survival assay revealed that incubation with ADSC CM aided HDFs to resist free radicals induced by tbOOH. In addition, activities of superoxide dismutase and glutathione peroxidase were enhanced in the ADSC-CM treated HDFs which confirmed the study hypothesis that ADSCs protect HDFs through antioxidant action. In a cell cycle analysis, ADSC-CM treatment reversed the apoptotic cell death induced by tbOOH and caused a decrease of sub-G1 cells with respect to untreated cells. The anti-apoptotic effect of ADSC-CM was also reproduced by caspase-3 activity assay. CONCLUSION: These results suggest that ADSCs have potent antioxidant activity and protect HDFs from oxidative injury by decreasing apoptotic cells. Therefore, ADSCs and ADSC-CM are good candidates for control and prevention of skin damage from free radicals in various skin conditions. PMID- 17870416 TI - Financial support for research training and career development in complementary and alternative medicine from the National Institutes of Health. AB - Research careers are a relatively new reality for complementary and alternative medicine (CAM) practitioners (eg, chiropractors, naturopaths, doctors of oriental medicine, etc). Before the establishment in 1998 of the National Center for Complementary and Alternative Medicine (NCCAM) as part of the National Institutes of Health (NIH), there were few funding resources available for those interested in a CAM research career and fewer still feasible paths. Now, however, NCCAM provides a broad array of research training and career development awards for those seeking a long-term career in CAM research. These awards include predoctoral and postdoctoral fellowships, individual career development awards, and institutional training awards. The goal of this article is to provide information about current research training funding opportunities from NCCAM and NIH as a whole that are available to CAM practitioners in the context of the historical challenges of transitioning from a clinical career in CAM practice to a CAM research career. PMID- 17870418 TI - The reproducibility of a clinical grading system of motor control in patients with low back pain. AB - OBJECTIVE: Over the past decade, instrument and palpation methods for quantifying the activation and recruitment of the transversus abdominis and lumbar multifidus have been proposed. Palpation methods however have recently been described and therefore have been subjected to little evaluation. One such palpation method is the Wisbey-Roth grading system. The recruitment of the transversus abdominis and lumbar multifidus is assessed in a series of functional body positions and movements. The ability to recruit these muscles is quantified by assigning 1 of 6 defined grades. The purpose of this study was to investigate the reproducibility of this grading system. METHODS: A total of 2 meetings and 3 pilot trials were held with raters before commencement of the study to establish an agreed grading system protocol. Interrater reproducibility was investigated using a Latin square repeated measures design. Thirty-four subjects (62% male and 38% female; age range, 15-70 years) with a history of low back pain participated. A total of 4 practicing physiotherapists and 1 sports medicine physician graded subjects using the Wisbey-Roth grading system protocol. RESULTS: Pair-wise weighted kappa values ranged from -0.01 (95% confidence interval [CI], -0.33 to 0.31) to 0.56 (95% CI, 0.25 to 0.87), with average weighted kappa being 0.29. The intraclass correlation coefficient (2,1) was 0.30 (95% CI, 0.15 to 0.48), and the standard error of the measurement was 1.6 units. CONCLUSIONS: The Wisbey-Roth grading system shows fair to poor reproducibility between raters. Therefore, it should not be used to exchange meaningful information between clinicians. Recommendations are made for further research and toward improving its reproducibility. PMID- 17870417 TI - Comparison of posteroanterior spinal stiffness measures to clinical and demographic findings at baseline in patients enrolled in a clinical study of spinal manipulation for low back pain. AB - OBJECTIVE: A system for measuring posterior-to-anterior spinal stiffness (PAS) was developed for use in clinical trials of manipulation for low back pain (LBP). The current report is an analysis of the baseline PAS data, with particular emphasis on relationships between PAS and clinical and demographic characteristics. METHODS: Posterior-to-anterior spinal stiffness measurements were recorded over the spinous processes of the lumbar spines from patients who had LBP. The system uses electronic sensors to record displacement and force, whereas a human operator provides the force of indentation. Clinical and outcome measures were compared with spinal stiffness. RESULTS: We recruited 192 patients (89 female and 103 male; average age, 40.0 years; SD, 9.4 years). The average Roland-Morris score was 9.7 (SD, 3.2) on a 24-point scale. The Visual Analog Scale pain scores were 55.7 (SD, 20.9) on a 100-mm scale. Stiffness values ranged from 4.16 to 39.68 N/mm (mean, 10.80 N/mm; SD, 3.72 N/mm). Females' lumbar spines were, on the average, 2 N/mm more compliant than males (P < .001). CONCLUSIONS: The PAS system of computer-monitored equipment with human operation performed well in this clinical study of LBP. Spinal stiffness was found to be different between males and females, and age and body mass index were related to PAS. We found no significant relationship between the severity or chronicity of the LBP complaint and spinal stiffness. There was little agreement between the stiff or tender segments identified by the clinicians using palpation and the segment that measured most stiff using the PAS device. PMID- 17870419 TI - The effect of combining manual therapy with exercise on the respiratory function of normal individuals: a randomized control trial. AB - OBJECTIVE: The objective of this study was to explore the effect of combining manual therapy with exercise on respiratory function in normal individuals. METHODS: The study design was a randomized control trial. Forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) were measured in 20 healthy, nonsmoking individuals before and after 3 interventions: exercise only, chiropractic manual therapy only, and manual therapy followed by exercise. The participants, 18 to 28 years of age, were randomly allocated to a control and 3 intervention groups. Each participant underwent 6 sessions of interventions over a 4-week period. RESULTS: The exercise only group showed a significant decrease in FVC (P = .002, generalized linear model [GLM]) and FEV1 readings (P = .0002, GLM). The manual therapy only group showed a significant increase in FVC (P = .000, GLM) and FEV1 (P = .001, GLM). The group that received both manual therapy and exercise showed increases in FVC and FEV1 immediately after manual therapy followed by an additional increase after exercise. The overall increase in this group was not statistically significant. Participants in the control group showed no change in FVC or FEV(1). CONCLUSIONS: Manual therapy appears to increase the respiratory function of normal individuals. The potential for this intervention administered before exercise to permit additional tolerance within the respiratory system that could allow an extended exercise program than was previously possible is discussed. PMID- 17870420 TI - Interexaminer reliability of the prone leg length analysis procedure. AB - OBJECTIVE: The purpose of this study was to perform an interexaminer reliability evaluation of the prone leg length analysis procedure. METHODS: Two chiropractors each examined a series of 45 patients with a history of low back pain. Patients were in the prone position, with the knees in both extended and flexed positions, and with the head rotated right and left. The clinicians were asked to determine the side of the short leg with knees extended and if a change in leg length occurred with head rotation or when the knees were flexed. They were also asked to visually judge the amount of leg length differential by categorizing the difference as either less than 0.25, 0.25 to 0.5, 0.5 to 0.75, or more than 0.75 in. The head rotation portion of the test was performed only with patients (n = 22) in whom the leg length differential was determined to be less than 0.25 in. RESULTS: kappa statistics and frequency distributions were calculated for each of the respective observations. Reliability of determining the side of the short leg with knees extended was good at 82% agreement (kappa = 0.65) but fair for determining the amount of leg length difference at 67% agreement (kappa = 0.28). Reliability of the head rotation testing procedure was extremely poor, with only 50% and 45% agreement about the observed change in leg length with the head rotated left and right, respectively (kappa = 0.04, kappa = -0.195). There was no significant correlation found between the side of reported pain by the patient and the side of the short leg as noted by either clinician (chi2 = 0.55, P = .91, and chi2 = 1.55, P = .67). All of the patients (100%) were judged to have a leg length difference by both clinicians. When the knees were flexed, there was 93% agreement that the short leg became longer (43/45 cases), with no reported cases of the short leg getting shorter. Calculation of kappa statistics was confounded for these last 2 observations because of extremely high prevalence bias. CONCLUSIONS: The results indicate that 2 clinicians show good reliability in determining the side of the short leg in the prone position with knees extended but show poor reliability when determining the precise amount of that leg length difference. The head rotation test for assessing changes in leg length was unreliable in this sample of patients. There does not appear to be any correlation between the side of pain noted by the patient and the side of the short leg as observed by the clinicians; all 45 patients in this sample were found to have a short leg by both clinicians. PMID- 17870421 TI - Magnetic resonance imaging of the triangular fibrocartilage complex lesions: a comprehensive clinicoradiologic approach and review of the literature. AB - OBJECTIVE: This article illustrates the frequent lesions of the triangular fibrocartilage complex (TFCC) by means of magnetic resonance imaging. METHODS: We performed a retrospective chart review of the magnetic resonance images of 109 patients from our database. All subjects had history of trauma, and all underwent both radiographic and magnetic resonance imaging examination of the wrist. The changes (degeneration, tears) of the TFCC were assessed. RESULTS: Ten patients were excluded because of incomplete imaging protocol (4 patients) and low-quality images (6 patients). From the 99 wrists remaining, the TFCC was normal in 30 (30.3%). Degenerative changes were found in 40 (40.4%) wrists. Partial and complete tears were present in 17 (17.1%) and 12 (12.1%) wrists, respectively. CONCLUSION: The TFCC lesions in acute traumatic wrists should not be overlooked; they may contribute to wrist pain and disability after treatment of existing bone injuries. PMID- 17870422 TI - Development of an evidence-based application and rubric for evaluating applicants' qualifications for promotion to professor. AB - OBJECTIVE: Every promotion committee is challenged by the need to make value judgments on the quantity and quality of peer work. Decisions based upon subjective assessments may not do justice to the applicant's or the institution's needs. The purpose of this article is to (1) describe the process a college promotion committee used to increase the objectivity brought to this activity, (2) present the tools developed that facilitated the collection and evaluation of faculty work, and (3) describe their usage in a promotion cycle. METHODS: The Professor Promotion Committee met weekly for 6 months engaging in lengthy and comprehensive discourse to capture the breadth of scholastic and service activities normally engaged in by faculty. RESULTS: The committee's work culminated in the development of 4 electronic applications soliciting specific evidence aligned with faculty work and 1 scoring rubric tied directly to the e applications. More than 55 activities were identified, divided into 4 levels of accomplishment using quantitative and qualitative criteria and weighted according to their centrality to faculty work and relative importance to the institution. Each activity was assigned to one of the following categories: teaching/academic support, scholarship/research, service, and professional development. A consensus score based upon the evidence was used to generate promotion discussions. CONCLUSIONS: The committee believes the online application aids applicants in recognizing the breadth and depth of promotable work. It provides them the opportunity to structure their work in ways that enhance their chances for promotion. The evidence-based rubric helps to reduce subjectivity in the evaluation process. PMID- 17870423 TI - Acute intracranial subdural hematoma after epidural steroid injection: a case report. AB - OBJECTIVE: Conservative treatment of lumbar radiculopathy includes bed rest, oral medications, physical therapy, spinal manipulation, mobilization, and epidural steroid injections. Intracranial subdural hematoma after accidental dural puncture is a rare and life-threatening complication of epidural steroid injections. In this report, we present a case of subacute intracranial subdural hematoma that developed after epidural steroid injection. CLINICAL FEATURES: A 40 year-old man was admitted to our clinic with severe persistent headache and vomiting for 2 days after epidural steroid injection for right leg pain. INTERVENTION AND OUTCOME: The patient was hospitalized for epidural steroid injection for right leg pain in our pain clinic and was discharged the same day. Twenty-four hours later, he started having a headache. Despite the use of oral analgesics, his headache worsened, and he began to vomit particularly in the upright position. Magnetic resonance imaging of the brain displayed a right frontal subdural hematoma. The headache was relieved after strict bed rest, intravenous hydration, and analgesics. The patient was discharged with full recovery after 1 week. CONCLUSION: Intracranial subdural hematoma after accidental dural puncture during epidural steroid injection is a rare complication. Persistent headache should be evaluated carefully for possible intracranial hematomas. PMID- 17870424 TI - A case of a potential manipulation responder whose back pain resolved with flexion exercises. AB - OBJECTIVE: Researchers have begun to investigate the value of subgrouping patients with back pain to improve clinical outcomes; one method is the development of clinical prediction rules. To be of clinical value, it is important that subgroups identify distinct categories of patients with an associated optimal treatment. This case study raises the suggestion that subgroups identified in this way may not represent distinct categories. CLINICAL FEATURES: A patient with sudden-onset back pain, who had 4 of 5 criteria for a clinical prediction rule said to identify responders to manipulation, was successfully treated using repeated flexion in lying exercises. OUTCOMES: Pain numeric score and Roland-Morris Disability Questionnaire were used to measure changes in pain and function. Pain score changed from 9/10 to 0/10 and disability score from 19/24 to 0/24 after 1 week and at 1 and 6 months of follow-up. CONCLUSION: We have presented a case study that was positive for 4 of 5 items of the clinical prediction rule for manipulation responders, but this patient was successfully treated with flexion exercises. The clinical prediction rule may not represent a discrete subgroup but may include patients who can be effectively managed in other ways. PMID- 17870425 TI - Early-onset multiple myeloma: an illustrative case report. AB - OBJECTIVE: This case study describes a patient diagnosed with early manifestations of multiple myeloma and illustrates relevant aspects of differential diagnosis and the use of laboratory, radiologic, and advanced imaging techniques to aid in establishing the diagnosis and issues of management. CLINICAL FEATURES: A 36-year-old male student experienced midback pain that occurred primarily at night in conjunction with fever and unexplained weight loss. Minor trauma induced a significant fracture and an occult fracture in the upper extremity. Physical examination revealed an elevated temperature indicating a fever of undetermined etiology. Plain radiographs revealed diffuse osteoporosis of the thoracic spine. Laboratory tests revealed anemia, hypercalcemia, and abnormal monoclonal paraprotein. Magnetic resonance imaging revealed a fracture with poor healing and an occult fracture in the upper extremity. INTERVENTION AND OUTCOME: The patient was initially assessed for fever of undetermined etiology in association with nocturnal midback pain. Although considered a disease of the geriatric population, subsequent laboratory and radiologic evaluations established a diagnosis of early-onset multiple myeloma. Early recognition and referral with comanagement by an oncologist provided optimum care. Early-onset cases of multiple myeloma tend to have a more favorable response to treatment as compared with cases diagnosed in the geriatric population. CONCLUSION: Multiple myeloma should be a consideration when a patient presents with nocturnal back pain and fever of undetermined etiology. Differentiating multiple myeloma from other causes of back pain is especially important in making management decisions. With a precise history and physical diagnosis, the diagnosis may be suspected, but confirmation must rely on ancillary investigations. Multiple myeloma is frequently accompanied by a poor prognosis, but early-onset cases generally respond more favorably to interventions. PMID- 17870426 TI - Identification and characterization of a 38 kDa glycoprotein functionally associated with mating activity of Paramecium primaurelia. AB - In Paramecium primaurelia mating interactions take place immediately after mixing mating-competent cells of opposite mating types. The cells clump in clusters (mating reaction) and then separate in pairs. Previous results have shown that sialic acid-containing glycoconjugates are present on the cell surface and are involved in mating-cell pairing. In order to identify the sialic acid-containing glycoprotein(s), we first metabolically radiolabelled non-mating-competent cells with D-[6-(3)H]galactose, and then analyzed the radiolabelled proteins by anion exchange chromatography. We characterized a 38 kDa (gp38) sialic acid-containing glycoprotein and raised the corresponding polyclonal antibody by means of which we localized the antigen at the level of the oral region of non-mating-competent cells and on the ciliary surface of mating-competent cells. Immunoblot analysis of the ciliary protein fraction showed that the anti-gp38 serum interacted with a 38 kDa protein in both mating types I and II cells. We also demonstrated the functional activity of gp38 in the mating reaction by means of anti-gp38 antibody competition assays. PMID- 17870427 TI - Morphogenesis of the marine spirotrichous ciliate, Trachelostyla pediculiformis (Cohn, 1866) (Ciliophora, Stichotrichia), with consideration of its phylogenetic position. AB - The cortical development during binary fission of the relatively poorly known stichotrich ciliate, Trachelostyla pediculiformis (Cohn, 1866) Borror, 1972, found in coastal waters near Qingdao, China, was investigated using the protargol impregnation method. The morphogenetic process reveals some pretty unusual characteristics, which do not follow the Oxytricha-pattern: (1) the parental oral apparatus is entirely renewed from an oral primordium formed de novo in the proter; (2) in the proter, the parental undulating membranes are not involved in the formation of the newly formed oral primordium; both undulating membrane anlagen (UM-anlage) and frontoventral-transverse cirral anlagen (FVT-anlagen) develop from the oral primordium in the proter; (3) the dorsal kineties (DK) are generated in a unique way, that is, in both dividers, two separate groups of DK anlagen develop in the right- and left-most DK, generate all the DK and evolve to replace the old structures; (4) three caudal cirri are formed at the posterior ends of three right-most dorsal kinety anlagen; (5) eight frontal, five ventral and five transverse cirri are derived from six streaks, namely, the UM-anlage and 5 FVT-anlagen; the cirri are segregated from these anlagen in the pattern 1:3:3:3:4:4 (from left to right) in the Oxytricha mode. Based on both SSrRNA gene sequencing and morphogenetic data, the systematic positions of the genus Trachelostyla Borror, 1972 as well as the family Trachelostylidae Small and Lynn, 1985 are briefly analyzed. The results indicate that this genus/family could be a highly isolated lineage and might be ancestral to other well-known oxytrichids. PMID- 17870428 TI - Whither papillon? Future directions for contact radiotherapy in rectal cancer. AB - Although contact radiotherapy was developed 70 years ago, and is highly effective with cure rates of over 90% for early rectal cancer, there are few centres that offer this treatment today. One reason is the lack of replacement of ageing contact X-ray machines, many of which are now over 30 years old. To address this problem, the International Contact Radiotherapy Evaluation (ICONE) group was formed at a meeting in Liverpool in 2005 with the aim of developing a new contact X-ray unit and to establish clinical protocols that would enable the new machine to safely engage in the treatment of rectal cancer. As a result of these efforts, a European company is starting production of the new Papillon RT-50 machine, which will be available shortly. In addition, the ICONE group is planning an observational study on contact X-ray and transanal endoscopic microsurgery (CONTEM) for curative treatment of rectal cancer. This protocol will ensure standardised diagnostic procedures, patient selection and treatment in centres across the world and the data will be collected prospectively for analysis and audit. It is hoped that the CONTEM trial will provide the scientific evidence that is needed to obtain a broader acceptance of local contact radiotherapy as a treatment option for selected cases with early stage rectal cancer. PMID- 17870429 TI - Screening, early detection, and trends for melanoma: current status (2000-2006) and future directions. AB - In the past 5 years, there have been notable strides toward the earlier recognition and discovery of melanoma, including new technologies to complement and augment the clinical examination and new insights to help clinicians recognize early melanoma. However, incidence and mortality rates throughout most of the developed world have risen over the past 25 years, while education and screening, potentially the best means for reducing the disease, continue to be severely underutilized. Much progress needs to be made to reach middle-aged and older men and persons of lower socioeconomic status who suffer a disproportionate burden of death from melanoma. Worldwide melanoma control must also be a priority, and comprehensive educational and screening programs should be directed to Northern Ireland and a number of Eastern European nations, whose 5-year survival rates range between 53% and 60%, mirroring those of the United States and Australia more than 40 years ago. LEARNING OBJECTIVE: After completing this learning activity, participants should be aware of the most recent melanoma epidemiologic data, both in the United States and internationally; worldwide early detection and screening programs; clinical strategies to recognize and improve the detection of early melanoma; the latest technologies for early detection of melanoma; and public and professional education programs designed to enhance early detection. PMID- 17870430 TI - Staged excision versus Mohs micrographic surgery for lentigo maligna and lentigo maligna melanoma. AB - BACKGROUND: Lentigo maligna (LM) is a relatively common tumor with increasing prevalence and substantial morbidity. A variety of treatment modalities are available, though margin-control surgery offers the highest cure rate. We were interested in comparing long-term outcomes of Mohs micrographic surgery (MMS) versus staged excision with permanent sections (SE) for treating LM or LM melanoma (LMM). METHODS: Comparative study consisting of retrospective chart review from our private practice. RESULTS: Fifty-seven patients (31 male, 26 female, mean age at diagnosis 69.1 +/- 10.1 years) were treated in our office for LM (50) or LMM (9) between January 1986 and December 2001. Forty-one tumors (71%) were located on the head and neck. Fifty-three of the 59 tumors (90%) were primary, and 6/59 (10%) were recurrent at the time of initial treatment. Forty one tumors (36 LM, 5 LMM) were treated with SE, and 18 (14 LM, 4 LMM) were treated with MMS. The mean preoperative lesion size (1.5 +/- 0.2 cm2 for SE; 1.2 +/- 0.4 cm2 for MMS), mean postoperative defect size (7.1 +/- 1 cm2 for SE; 7.1 +/- 1.4 cm2 for MMS), and the ratio of postoperative defect to preoperative lesion size (7.9-fold increase for SE, 11.2-fold increase for MMS) were similar between the cohorts. Mean number of stages for clear margins were similar, with 1.8 +/- 0.2 stages (range: 1-7) for SE and 2.0 +/- 0.2 stages (range: 1-4) for MMS; clear margins were obtained in one or two stages in 85% of cases for SE and in 67% for MMS. Three recurrences (3/41; 7.3%) occurred in the SE group while 6 recurrences (6/18; 33%) occurred in the MMS group (P < .025). The mean follow-up duration was 95 months (range: 60-240) in the SE group and 117.5 months (range: 61-157) in the MMS group. LIMITATIONS: Results are limited to a single practice site and fewer patients underwent MMS compared to SE. Patients were not randomized as cases were ascertained retrospectively. CONCLUSION: Staged excision of LM and LMM is associated with a significantly lower recurrence rate with no difference in surgical defect size compared to MMS. To our knowledge, this is the first study directly comparing these two surgical techniques for managing this form of melanoma. Our extended follow-up duration exceeds that of most previous reports. PMID- 17870431 TI - Giant verrucous porokeratosis of Mibelli mimicking psoriasis in a patient with psoriasis. AB - Porokeratosis of Mibelli is a disorder of epidermal keratinization characterized by annular plaques with an atrophic center surrounded by a keratotic wall. We report a case of a giant verrucous porokeratosis of Mibelli mimicking psoriasis that developed in a patient with psoriasis and therefore went unrecognized for a long time. Histologically the lesion combined features of porokeratosis at the periphery and of psoriasis at its center, a picture recently described as "psoriasis encircled by porokeratosis." The possible pathogenetic relationship between psoriasis and the development of porokeratosis is also discussed. PMID- 17870432 TI - Expression of p53 in the evolution of squamous cell carcinoma: correlation with the histology of the lesion. AB - BACKGROUND: The evolution of squamous cell carcinoma (SCC) on sun-exposed areas is a multistep process triggered by ultraviolet radiation (UVR), in which precursor lesions exist. However, the exact classification of the various lesions in this process, mainly solar keratosis (SK), is still disputed, and its pathogenesis requires further clarification. OBJECTIVE: To further elucidate the evolution of SCC on sun-damaged skin by correlating the levels of p53 protein expression, a parameter that reflects UVR damage to cells, and the morphology of the lesions that develop on sun-exposed areas. METHODS: Biopsy specimens from normal skin (n = 4), normal skin with various degrees of solar elastosis (SE) (n = 16), various degrees of SK (n = 17) and SCCs from sun-exposed (n = 12) and sun protected (n = 7) areas were stained with anti-p53 antibodies. A semiquantitative evaluation of the degree of staining was performed and correlated with the histological features. RESULTS: Nuclear staining in keratinocytes was observed already in normal skin with mild SE and was increased gradually to its highest level of expression in advanced SK. It was also expressed in SCCs, but to a lesser degree. Statistical analysis revealed association between the morphology of the lesion and the level of p53 expression (P < .01); it also showed that in general the level of p53 is correlated with the histology of the lesion (P < .001). Furthermore, with regard to p53 expression, two groups of lesions exist: one showing a low level of expression of p53 that includes normal skin, skin with various degrees of SE and SCC from sun-protected areas, and a second group showing a high level of expression that includes SK and SCC occurring on sun damaged skin. LIMITATION: This is an immunohistochemical study of relatively few cases and in which the antibody detects all types of p53 protein. CONCLUSIONS: This study furnishes further evidence that the development of SCC on sun-damaged skin is a gradual process not only morphologically but also on the molecular level. The process starts already in normal-appearing epidermis with SE. In that respect, SK should be regarded as a part of the continuum in the development of SCC, analogous to the situation in other epithelia. The molecular events involved in the development of SCC on sun-exposed areas may be different from those involving the development of SCC on sun-protected areas. PMID- 17870433 TI - Superimposed segmental manifestation of polygenic skin disorders. AB - In common acquired skin disorders with a polygenic background such as psoriasis, a linear or otherwise segmental arrangement may sometimes be noted. The segmental involvement tends to be rather severe and may be associated with milder, nonsegmental lesions of the same disorder. Such cases may be best explained by an early postzygotic event in the form of loss of heterozygosity involving one of the genes that predispose to the disorder. The following pertinent examples are reviewed in this article: psoriasis vulgaris, pustular psoriasis, atopic dermatitis, lichen planus, systemic lupus erythematosus, pemphigus vulgaris, vitiligo, graft-versus-host disease, granuloma annulare, erythema multiforme, and drug eruption to ibuprofen. Such cases should not be categorized as a "type 2 segmental manifestation" because this term exclusively applies to monogenic traits, whereas in polygenic disorders the more descriptive term "superimposed segmental manifestation" seems appropriate. The concept of early loss of heterozygosity offers a plausible explanation as to why: the segmental involvement tends to appear at a rather young age and often precedes the development of milder, nonsegmental lesions of the same disorder; the segmental lesions are notoriously difficult to treat; and family members may show the disorder in its nonsegmental form. On the other hand, the theory of isolated versus superimposed segmental manifestation may help to elucidate the origin of polygenic skin disorders at the molecular level. PMID- 17870434 TI - The interplay of innate immunity, adaptive immunity, and autoimmunity. PMID- 17870436 TI - Expanding the microcomedone theory and acne therapeutics: Propionibacterium acnes biofilm produces biological glue that holds corneocytes together to form plug. AB - The Propionibacterium acnes biofilm has previously been shown to exist via genomic studies and to make a biological glue which allows for adherence to follicular walls. This gylcocalyx polymer secreted by P acnes also finds its way into sebum composition where it causes the adhesiveness of keratinocytes leading to comedones. An appreciation of P acnes biofilms and secretions has implications in immunogenicity of the organism, clinical course of acne, and therapy for comedonal and inflammatory acne. PMID- 17870437 TI - Dermatologists in industry. PMID- 17870438 TI - Dermoscopy for diagnosis of pediculosis capitis. PMID- 17870439 TI - Response to Beutner and Plunkett. PMID- 17870440 TI - In reference to the October 2004 comprehensive overview of rosacea therapy. PMID- 17870441 TI - Reporting of number needed to treat and its difficulties. PMID- 17870443 TI - What a difference an image makes. PMID- 17870444 TI - Breast carcinoma in a male: importance of hormonal receptor expression and possibility of a familial cancer syndrome. PMID- 17870445 TI - Odonto-onycho-dermal dysplasia syndrome. PMID- 17870446 TI - Direct plasmid DNA encapsulation within PLGA nanospheres by single oil-in-water emulsion method. AB - Plasmid DNA was encapsulated within poly(d,l-lactic-co-glycolic acid) (PLGA) nanospheres by using polyethylene glycol (PEG) assisted solubilization technique of plasmid DNA in organic solvents. Plasmid DNA was solubilized in an organic solvent mixture composed of 80% methylene chloride and 20% DMSO by producing PEG/DNA nano-complexes having an average diameter less than 100 nm. DNA could be solubilized in the organic solvent mixture to a greater extent with increasing the weight ratio of PEG/DNA. PLGA nanospheres encapsulating DNA were successfully prepared by the single O/W emulsion method. They exhibited greater loading efficiency and better structural integrity, compared to those prepared by the W/O/W double emulsion method. Plasmid DNA could be successfully delivered to macrophage cells to express an exogenous gene. This new formulation enabled high loading of intact plasmid DNA within PLGA nanospheres useful for DNA vaccines. PMID- 17870447 TI - Non-viral gene transfection technologies for genetic engineering of stem cells. AB - The recent rapid progress of molecular biology together with the steady progress of genome projects has given us some essential and revolutionary information about DNA and RNA to elucidate various biological phenomena at a genetic level. Under these circumstances, the technology and methodology of gene transfection have become more and more important to enhance the efficacy of gene therapy for several diseases. In addition, gene transfection is a fundamental technology indispensable to the further research development of basic biology and medicine regarding stem cells. Stem cells genetically manipulated will enhance the therapeutic efficacy of cell transplantation. In this paper, the carrier and technology of gene delivery are briefly overviewed while the applications to the basic researches of biology and medicine as well as regenerative medical therapy are introduced. A new non-viral carrier and the cell culture system are described to efficiently manipulate stem cells. PMID- 17870448 TI - Formulation of an intermediate product from human serum albumin for the production of a solid dosage form. AB - The main objective of this study was to evaluate and to increase the processibility of a model protein (human serum albumin (HSA)) for preparation of an intermediate for a solid dosage form. The applicability of the solid forms is easier, and therefore their formulation is a promising method for the application of proteins. The layering of powdered cellulose with HSA solutions of different concentrations in a fluid bed apparatus with the top spray method was applied. The yield of this technique was very good, independently of the concentration of the applied solution. The HSA covered the particles (the HSA layer formed was smooth), but it caused aggregation of the cellulose particles, and spray-dried microparticles also formed. The proportion of optimum-sized particles (200-315 microm) decreased. The largest amount was detected for the samples prepared with liquid containing 15% HSA (about 2 times higher than the second best). Not only the size, but also the shape of the particles was changed. The alteration in this parameter caused a change in the flowability. This was likewise the best for the samples prepared with the liquid containing 15% HSA. The concentration of HSA in the fraction containing smaller particles was higher, because of the abrasion of the particles and the enrichment of the spray-dried HSA. The distribution of HSA in the large particles was uneven. The layering of powder cellulose can be applied to produce an intermediate from HSA for solid dosage forms, but the appropriate concentration of this protein solution must be optimized previously because HSA can act as a binder. The formation of large agglomerates must be eliminated, because the distribution of the active agent in these is very inhomogeneous. The present results indicated that the best value can be achieved with liquid containing between 12.5% (most homogeneous distribution of HSA) and 15% HSA (best flowability). PMID- 17870449 TI - Characterization of thermosensitive chitosan-based hydrogels by rheology and electron paramagnetic resonance spectroscopy. AB - Chitosan, an amino-polysaccharide, has been proposed as a promising biopolymer for tissue repair and drug delivery. Chitosan solutions containing glycerol-2 phosphate (beta-GP) have been described as injectable in situ gelling thermosensitive formulations, which undergo sol-gel transition at physiological pH and temperatures. This feature makes them suitable for the parenteral administration of drugs, especially for peptides and proteins. The aim of the present study was to get a deeper insight into the macro- and microstructure of chitosan/beta-GP systems. In addition to oscillating rheology, electron paramagnetic resonance (EPR) spectroscopy was applied to examine the microviscosity and pH inside the gels depending on the beta-GP concentration and to follow the loading and release of spin-labelled Insulin. All chitosan/beta-GP solutions showed a physiological pH ranging from 6.6 to 6.8 that did not change during gelation, irrespective of the proportion of beta-GP. The dynamics of the spin-labelled Insulin and its microviscosity inside the gels and during release were monitored by EPR spectroscopy. The results indicate that the Insulin was incorporated into the aqueous environment of the gel and was released in its native form. The in vitro drug release from the gels was governed by diffusion of drug from the gel matrix. A sustained release of Insulin was observed over a period of 2 weeks. Increasing the proportion of beta-GP increased the amount of released Insulin and the velocity thereof. PMID- 17870450 TI - Inhibitory effect of ketamine on phosphorylation of the extracellular signal regulated kinase 1/2 following brain ischemia and reperfusion in rats with hyperglycemia. AB - To determine if the inhibitory effects of ketamine on the extracellular signal regulated kinase (ERK) 1/2 are involved in reduction of the hyperglycemia exaggerated cerebral ischemic lesion, rats with normoglycemia, hyperglycemia, or hyperglycemia supplemented with ketamine were subjected to 15 min of forebrain ischemia, and then, reperfusion for 0.5, 1, and 3h. Phosphorylation of ERK1/2 in the brain tissues was assessed by immunohistochemistry and Western blot analysis. In rats with normoglycemia, we demonstrated a moderate increase of the ERK1/2 phosphorylation in the cingulum cortex and hippocampus CA3 following an ischemic intervention. It quickly dropped to control levels after reperfusion for 0.5h. In rats with hyperglycemia, however, the increase of the ERK1/2 phosphorylation in these areas was significantly higher in all animals reperfused. The neuronal death, detected by the TdT-mediated-dUTP nick end labeling assays, was found in the cingulum cortex (5.23+/-2.34, per high power feild) and hippocampus CA3 areas (6.29+/-3.68, per 1mm(2)) in hyperglycemic group after reperfusion for 3h. With ketamine treatment, the ERK1/2 phosphorylation in cingulum cortex and hippocampus CA1 and CA3 areas was found to be the same as that in normoglycemia rats. Our results suggest that hyperglycemia may increase the ischemic insult through modulation of the signal transduction pathways involving ERK1/2. The inhibitory effects of ketamine on the hyperglycemia-activated ERK1/2 phosphorylation are probably through inhibition of the N-methyl d-aspartate-mediated calcium influx, which subsequently reduce the hyperglycemia-exaggerated cerebral damage. PMID- 17870451 TI - Bioavailability of the phenolic compounds of the fruits (drupes) of Olea europaea (olives): impact on plasma antioxidant status in humans. AB - To examine the bioavailability of olive polyphenols and to correlate it with their antioxidant efficacy, plasma and urine from healthy volunteers who had consumed 20 olives were subjected to (a) GC-MS analysis for individual phenolics, (b) estimation of plasma total polyphenol content and (c) estimation of plasma total antioxidant potential. Olive polyphenols were absorbed and metabolized within the body, occurring in plasma mainly in the conjugated form with glucuronic acid and reaching C(max) in 1-2h. Excretion rates were maximum at 0 4h. Tyrosol and hydroxytyrosol increased in plasma after intervention. Total antioxidant potential increased (p<0.05). The results indicate that olive polyphenols possess good bioavailability, which is in accordance with their antioxidant efficacy. PMID- 17870452 TI - Protective roles of puerarin and Danshensu on acute ischemic myocardial injury in rats. AB - Ischemic heart diseases have been the leading cause of death in both developed and developing countries over the past decades. The aim of this study was to investigate the cardioprotective effects of the complex preparation (called Shenge), made of puerarin (isolated from Pueraria lobata Ohwi., also called Kudzu) and Danshensu (isolated from the Chinese herb, Salvia miltiorrhiza), on acute ischemic myocardial injury in rats and its underlying mechanisms. The left anterior descending (LAD) coronary artery was occluded to induce myocardial ischemia in the hearts of SD rats. Shenge was injected into the tail vein 15 min after occlusion at doses of 0, 30, 60, or 120 mg/kg body wt. ST elevation was then measured at 60, 120, and 240 min after Shenge administration. The ischemic size, serum levels of creatine kinase isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA), and ST elevation were measured after the rats were sacrificed. Shenge decreased ST elevation induced by acute myocardial ischemia, reduced ischemic size, serum levels of CK MB, LDH and MDA, and increased serum activity of SOD in a dose-dependent manner. The combined use of puerarin and Danshensu at a ratio of 1:1 showed the most effective activity. In conclusion, Shenge exerts significant cardioprotective effects against acute ischemic myocardial injury in rats, likely through its antioxidant and anti-lipid peroxidation properties, and thus may be an effective and promising medicine for both prophylaxis and treatment of ischemic heart disease. PMID- 17870457 TI - Role of physiotherapy in the management of chronic lung diseases: an overview of systematic reviews. AB - Four Cochrane respiratory reviews of relevance to physiotherapeutic practice are discussed in this overview. Physiotherapists aim to improve ventilation for people with respiratory disease, and approach this using a variety of techniques. As such, the reviews chosen for discussion consider a wide range of interventions commonly used by physiotherapists: breathing exercises, bronchopulmonary hygiene techniques and physical training for peripheral and respiratory muscles. The reviews show that breathing exercises may have beneficial effects on health related quality of life in asthma, and that inspiratory muscle training (IMT) may improve inspiratory muscle strength. However, the clinical relevance of increased respiratory muscle strength per se is unknown, and the longer-term effects of breathing exercises on morbidity have not been considered. One review clearly shows that bronchopulmonary hygiene techniques in chronic obstructive pulmonary disease (COPD) and bronchiectasis increase sputum production. Frequent exacerbation is associated with increased sputum and high bacterial load, suggesting that there may be important therapeutic benefit of improved sputum clearance. Future studies evaluating the long-term effects of bronchopulmonary hygiene techniques on morbidity are recommended. In the third review, the importance of pulmonary rehabilitation in the management of COPD is once again reinforced. Physiotherapists are crucial to the delivery of exercise training programmes, and it is likely that the effects of pulmonary rehabilitation extend to other important outcomes, such as hospital admission and re-admission. On the basis of the evidence provided by these Cochrane reviews, this overview highlights important practice points of relevance to physiotherapy, and recommendations for future studies. PMID- 17870458 TI - The incidence of cancer in patients with idiopathic pulmonary fibrosis and sarcoidosis in the UK. AB - BACKGROUND: The aim of this study was to use a longitudinal computerised health care dataset (The Health Improvement Network) to provide information on the overall incidence of cancer, and on the incidence of organ-specific cancers, in people with idiopathic pulmonary fibrosis (IPF) and sarcoidosis in comparison to the general population. METHODS: Incident cases of IPF and sarcoidosis were identified with up to four controls matched by age, gender and general practice. Cancer incidence rates were compared between cohorts using Cox regression and adjusting for age, gender and smoking habit. RESULTS: One thousand and sixty-four incident cases of IPF (mean age at diagnosis 71.5 years; 62.4% male) were identified. Overall, the incidence of cancer was increased in people with IPF compared to the general population (rate ratio 1.51; 95% CI 1.20-1.90), but this was largely due to a marked increase in the incidence of lung cancer (rate ratio 4.96; 95% CI 3.00-8.18). One thousand one hundred and fifty-three incident cases of sarcoidosis (mean age at diagnosis 47.0 years; 47.2% male) were identified. There was an overall increased incidence of cancer in sarcoidosis (rate ratio 1.65; 95% CI 1.22-2.24) and this was largely explained by an increase in the incidence of skin cancers (rate ratio 1.86; 95% CI 1.11-3.11). CONCLUSIONS: This study provides further evidence of a marked increase in the incidence of lung cancer in people with IPF, but we found no increase in the risk of other cancers. People with sarcoidosis did have an increase risk of skin cancers, but not cancers at other sites. PMID- 17870461 TI - The Cedar Project: a comparison of HIV-related vulnerabilities amongst young Aboriginal women surviving drug use and sex work in two Canadian cities. AB - BACKGROUND: In Canada, Aboriginal women and youth continue to be overrepresented amongst new cases of HIV, and are considered at increased risk for sex and drug related harm. Young women involved in sex work are particularly vulnerable. The purpose of this study is to determine HIV-related vulnerabilities associated with sex work amongst young Aboriginal women in two Canadian cities. METHODS: This study is based on a community-based cohort of Aboriginal young people (status and non-status First Nations, Inuit and Metis) between the ages of 14 and 30 who used injection or non-injection illegal drugs (street drugs) in the previous month. Participants lived in Vancouver, Canada, or Prince George, a remote, northern Canadian city. Between October 2003 and July 2005, 543 participants were recruited by word of mouth, posters, and street outreach. A baseline questionnaire was administered by Aboriginal interviewers, and trained nurses drew blood samples for HIV and HCV antibodies and provided pre- and post-test counselling. This study included 262 young women who participated at baseline. Analyses were conducted to compare socio-demographics, drug use patterns, injection practices, sexual experiences, and HIV and HCV prevalence between young women who reported being involved in sex work in the last 6 months (n=154) versus young women who did not (n=108). Logistic regression was used to identify factors independently associated with recent sex work involvement. RESULTS: Both sexual violence and drug using patterns were found to be markedly different for women having recently been involved in sex work. Multivariate analysis revealed daily injection of cocaine (AOR=4.4; 95% CI: 1.9, 10.1 and smoking crack (AOR=2.9; 95% CI: 1.6, 5.2) in the previous 6 months, and lifetime sexual abuse (AOR=2.5; 95% CI: 1.4, 4.4) to be independently associated with sex work. INTERPRETATION: Harm reduction and treatment programs that address historical and lifetime trauma amongst Aboriginal people and prioritize emotional and physical safety for young Aboriginal women involved in sex work are required. PMID- 17870462 TI - An evaluation of substrate degradation patterns in the composting process. Part 1: profiles at constant temperature. AB - This paper examines the patterns of 32 constant temperature substrate degradation profiles obtained from the composting literature, and evaluates the use of a single exponential model, a double exponential model and a non-logarithmic Gompertz model in describing their behaviour. Profiles were found to be predominantly either sigmoidal in shape, or to exhibit multi-phase behaviour, with a relatively small proportion of convex curves. Of the constant temperature profiles, 26 were either not well modelled by any of the above functions, or of such differing profiles that none of the above functions was applicable. Goodness of fit was measured using a normalised error function, and rated using a five category descriptive scale, ranging from excellent to poor. No fits rated as excellent were observed. Fits rated as good were obtained for three data sets when using a single exponential function, for two data sets when using a double exponential function, and for one data set when using the non-logarithmic Gompertz function. The remainder of the fits were rated as moderate to poor. It is concluded that the evidence supporting the use of the single exponential model, the double exponential model or the non-logarithmic Gompertz model to describe substrate degradation profiles generated at constant temperature is limited. Further work is suggested in order to establish standard procedures and a standard simulated composting mixture for substrate degradation studies and to build a more comprehensive set of long-term substrate degradation profile data at constant temperature, and under non-limiting moisture and oxygen concentration conditions. PMID- 17870463 TI - Characterization of municipal solid waste from the main landfills of Havana city. AB - The city of Havana, the political, administrative and cultural centre of Cuba, is also the centre of many of the economic activities of the nation: industries, services, scientific research and tourism. All of these activities contribute to the generation of municipal solid waste (MSW), which also impact other Cuban cities. Inadequate handling of waste and the lack of appropriate and efficient solutions for its final disposal and treatment increase the risk and possibility of contamination. The main difficulty in the development of a system of management of MSW lies in the lack of knowledge of the chemical composition of the waste that is generated in the country as a whole, and especially in Havana, where solid waste management decisions are made. The present study characterizes MSW in Havana city during 2004. The Calle 100, Guanabacoa and Ocho Vias landfills were selected for physical-chemical characterization of MSW, as they are the three biggest landfills in the city. A total of 16 indicators were measured, and weather conditions were recorded. As a result, the necessary information regarding the physical-chemical composition of the MSW became available for the first time in Cuba. The information is essential for making decisions regarding the management of waste and constitutes a valuable contribution to the Study on Integrated Management Plan of MSW in Havana. PMID- 17870464 TI - Ancestral and recently recruited global control of the Hox genes in development. AB - Genes from the Hox family are involved in the common task of providing nascent embryonic tissues with their positional identity. They are organised in clusters in most species. Mouse Hox genes are regulated in part by gene-proximal regulatory elements, but owe several of their essential properties to the use of global regulatory elements located outside the complexes. The clustered Hox genes in that sense behave as a single large locus. Genomic and sequence data from different animal species suggest that a concerted regulation of the Hox clusters, inherently coupled to their patterning properties, originated early during evolution and pre-figured the temporal colinearity of expression of vertebrate Hox genes. In addition, vertebrates have recruited novel global mechanisms to control the expression of linear subsets of Hox genes in specific embryonic structures. Several of such novel global regulatory circuits have recently been characterised at the molecular genetic level in the mouse. PMID- 17870465 TI - The structure of membrane associated proteins in eicosanoid and glutathione metabolism as determined by electron crystallography. AB - Membrane associated proteins in eicosanoid and glutathione metabolism (MAPEG) are involved in biosynthesis of arachidonic-derived mediators of pain, fever, and inflammation as well as in biotransformation and detoxification of electrophilic substances. Structure determination of microsomal glutathione transferase 1 using electron crystallography has provided the first atomic model of an MAPEG member. The homotrimer consists of three repeats of a four-helix transmembrane bundle with the largest extramembranous domain connecting the first and second helix and with a short proline rich loop on the same side between helices three and four. Residues of importance for intramolecular or intermolecular contacts as well as for stabilizing the active site have been identified and the results can be applied for interpreting structure-function relationship for similar MAPEG members. PMID- 17870467 TI - Structural basis of viral invasion: lessons from paramyxovirus F. AB - The structures of glycoproteins that mediate enveloped virus entry into cells have revealed dramatic structural changes that accompany membrane fusion and provided mechanistic insights into this process. The group of class I viral fusion proteins includes the influenza hemagglutinin, paramyxovirus F, HIV env, and other mechanistically related fusogens, but these proteins are unrelated in sequence and exhibit clearly distinct structural features. Recently determined crystal structures of the paramyxovirus F protein in two conformations, representing pre-fusion and post-fusion states, reveal a novel protein architecture that undergoes large-scale, irreversible refolding during membrane fusion, extending our understanding of this diverse group of membrane fusion machines. PMID- 17870468 TI - Versatility in ligand recognition by LDL receptor family proteins: advances and frontiers. AB - Proteins of the low-density lipoprotein receptor family transport cholesterol carrying particles into cells, clear protease-inhibitor complexes from the circulation, participate in biological signaling cascades, and even serve as viral receptors. These receptors utilize clusters of cysteine-rich LDL receptor type-A (LA) modules to bind many of their ligands. Recent structures show that these modules typically exhibit a characteristic binding mode to recognize their partners, relying primarily on electrostatic complementarity and avidity effects. The dominant contribution of electrostatic interactions with small interface areas in these complexes allows binding to be regulated by changes in pH via at least two distinct mechanisms. The structure of the subtilisin/kexin family protease PCSK9, a newly identified molecular partner of the LDLR also implicated in LDL-cholesterol homeostasis, also raises the possibility that the LDLR and its related family members may employ other strategies for pH-sensitive binding that have yet to be uncovered. PMID- 17870469 TI - Yeast surface display for protein engineering and characterization. AB - Yeast surface display is being employed to engineer desirable properties into proteins for a broad variety of applications. Labeling with soluble ligands enables rapid and quantitative analysis of yeast-displayed libraries by flow cytometry, while cell-surface selections allow screening of libraries with insoluble or even as-yet-uncharacterized binding targets. In parallel, the utilization of yeast surface display for protein characterization, including in particular the mapping of functional epitopes mediating protein-protein interactions, represents a significant recent advance. PMID- 17870470 TI - Phage display for engineering and analyzing protein interaction interfaces. AB - Phage display is the longest-standing platform among molecular display technologies. Recent developments have extended its utility to proteins that were previously recalcitrant to phage display. The technique has played a dominant role in forming the field of synthetic binding protein engineering, where novel interfaces have been generated from libraries built using antibody fragment frameworks and also alternative scaffolds. Combinatorial methods have also been developed for the rapid analysis of binding energetics across protein interfaces. The ability to rapidly select and analyze binding interfaces, and compatibility with high-throughput methods under diverse conditions, makes it likely that the combination of phage display and synthetic combinatorial libraries will prove to be the method of choice for synthetic binding protein engineering for broad applications. PMID- 17870471 TI - Modulating membrane protein stability and association by design. AB - Membrane proteins perform crucial communication functions across biological membranes. They represent important targets for therapies and have unique properties for biotechnological applications. Recently, the number of high resolution membrane protein structures has significantly increased and new insights into the sequence/structure relationships of transmembrane helical assemblies have been gained. Together with new experimental techniques, these advances have improved our understanding of membrane protein folding, stability, and recognition. Consequently, new design strategies are emerging that aim to target and stabilize simple transmembrane helical interfaces. PMID- 17870473 TI - Clinically significant changes in acute pain in a pediatric ED using the Color Analog Scale. AB - OBJECTIVE: The purpose of this study is to quantify, using the Color Analog Scale (CAS), the degree of change in pain severity required to achieve a clinically significant improvement in pain. METHODS: A prospective descriptive study, using convenience sampling of children aged 5 and 12 years presenting to a pediatric emergency department (ED) with acute pain, was done. Children were asked to mark their pain severity on a previously validated CAS. After a pain intervention, the child was again asked to mark their pain intensity on the CAS and asked to describe the relative change in their pain. The main outcome measure was to quantify the smallest change required for the child to state that their pain was improved. RESULTS: One hundred twenty-six children with a mean age of 8.6 years (SD, 2.8 years) were enrolled. Males accounted for 56%. Pain was traumatic in 47.6% and nontraumatic in 52.4%. Of the 126 pain comparisons made, 28 children described their pain as "the same" and had a mean change in score of -0.10 cm (95% confidence interval [CI], -2.27 to 2.07 cm). Pain was judged to be a "little less" in 58 children, and the CAS score changed by a mean of -2.4 cm (95% CI, 3.15 to -1.72 cm). In the 29 children who judged their pain to be "much less," the CAS score decreased by a mean of -5.4 cm (95% CI, -6.50 to -4.40). CONCLUSION: A decrease on the CAS pain scale of 2.4 cm (95% CI, 2.95-1.92) is a clinically significant change in pain for children aged 5 to 12 years with acute pain. The CAS is a valuable tool in assessing responses to pain interventions. PMID- 17870474 TI - The association of a decreased level of awareness and blood alcohol concentration with both agitation and sedation in intoxicated patients in the ED. AB - OBJECTIVE: This study was conducted to compare the level of awareness as determined by serial bispectral index (BIS) electroencephalogram scores to a standardized Altered Mental Status (AMS) scale used to define a patient's clinical level of agitation or sedation, and the patient's concurrent breath/blood alcohol concentration (BAC). METHODS: This was an institutional review board-approved, prospective observational study of a convenience sample of patients who presented to the emergency department (ED) with the chief complaint of ethanol (ETOH) intoxication between July 19, 2003, and March 27, 2004. The AMS scale is a 9-point scale: -4 is unresponsive, 0 is normal examination, and +4 is extremely agitated. After ETOH was detected by breath analyzer, enrolled patients had a BIS monitor probe applied to their forehead. Baseline BAC, BIS, and AMS scores were recorded independently of the patients' caregivers. Bispectral index and AMS scores were repeated every 20 minutes for 1 hour. The patient's diagnosis, disposition, (any) complications, and total time in department were recorded. RESULTS: Ninety-eight patients were enrolled in the study. The median presenting AMS score was -1. The mean total time in department was 402.6 minutes (SD, 196.4; range, 246-906 minutes). The mean presenting BIS score was 77.6 (SD, 17.9; range, 26-98). The mean presenting BAC was 0.229 (SD, 0.07; range, 0.049 0.43). The mean BIS index varied from 59.6 +/- 16.9 for AMS scores of -4, to 96.3 +/- 2.7 for AMS scores of 0, to 90.5 +/- 4.9 for AMS scores of 4. The AMS scale correlated with the BIS scale (Spearman's rho = 0.67, P < or = .001), but did not correlate with BAC (Spearman's rho = -0.14, P = 0.15). CONCLUSIONS: Changes in the AMS scale corresponded to changes in the BIS index score. A decreased level of awareness, as determined on the BIS index, was observed in patients who were either agitated or sedated by the AMS. We conclude that both agitated and sedated patients with ETOH intoxication show decreases in their level of awareness. Therefore, the AMS scale, which includes both agitation and sedation, is a valid measure of a patient's decreased level of awareness. PMID- 17870475 TI - How sensitive is the synovial fluid white blood cell count in diagnosing septic arthritis? AB - OBJECTIVE: This study was conducted to determine the sensitivity of the current standard for synovial fluid leukocytosis analysis in diagnosing infectious arthritis or a septic joint. How accurate is the standard synovial fluid white blood cell (WBC) cutoff of 50,000 WBC/mm3 to rule out septic arthritis? METHODS: We conducted a retrospective study at an urban tertiary care medical center with 50,000 adult emergency department visits per year. The study population consisted of patients with infectious arthritis confirmed by synovial fluid culture growth of a pathogenic organism. The study period lasted from January 1996 to December 2002. Extracted data included synovial fluid leukocyte count, Gram's stain, culture, past medical history, and discharge diagnosis. Fisher exact test was used to compare proportions. Sensitivity and means were calculated with 95% confidence intervals (CI). RESULTS: There were 49 culture-positive synovial fluid aspirates in the 6-year study period. Nineteen (39%) of 49 patients (95% CI, 25% 52%) had a synovial WBC of less than 50,000/mm3 and 30 (61%) of 49 patients (95% CI, 48%-75%) had a synovial WBC of more than 50,000/mm3. The sensitivity of the 50,000 synovial WBC/mm3 cutoff was 61% (95% CI, 48%-75%). Twenty-seven (55%) of 49 patients had a negative Gram's stain (95% CI, 41%-69%) and 15 (56%) of 27 patients (95% CI, 37%-74%) with negative Gram's stain had a synovial WBC of less than 50,000/mm3. CONCLUSION: A synovial fluid WBC cutoff of 50,000/mm3 lacks the sensitivity required to be clinically useful in ruling out infectious arthritis. PMID- 17870476 TI - Supine vs semirecumbent and upright 12-lead electrocardiogram: does change in body position alter the electrocardiographic interpretation for ischemia? AB - OBJECTIVE: The goal of this study was to determine if a change in body position alters the 12-lead electrocardiographic (ECG) interpretation for ischemia and ST segment elevation, the latter having direct implications for initial patient management in the emergency department. METHODS: Twelve-lead ECGs were sequentially obtained from a convenience sample of healthy adult volunteers in 3 positions (supine, 0 degrees; inclined, 45 degrees; and upright, 90 degrees). The tracings were randomized, blinded, and then independently read by 2 trained emergency medicine physicians who also assessed for the presence of ischemia and ST-segment elevation myocardial infarction. RESULTS: Seventy-five subjects were enrolled, with 7 (9%; 95% confidence interval [CI], 4-18) having ischemia on the supine ECG, 9 (12%; 95% CI, 6-22) on the incline, and 9 on the upright tracings. ST-segment elevation myocardial infarction pattern was present on 2 (3%; 95% CI, 0-9) supine, 2 inclined, and 2 upright ECGs. CONCLUSIONS: Changes in body position result in some ischemic variations of the 12-lead ECG. PMID- 17870477 TI - Recovery from a psychotropic drug overdose tends to depend on the time from ingestion to arrival, the Glasgow Coma Scale, and a sign of circulatory insufficiency on arrival. AB - PURPOSE: The aim of this study was to investigate which factors on arrival correlate with the duration of unconsciousness induced by a psychotropic drug overdose. BASIC PROCEDURE: Patients were 175 consecutive intubated patients unconscious due to psychotropic drug overdose. They were divided into 2 groups, an "early" group in which the patients were extubated within 2 days from hospitalization, and a "delayed" group who were not extubated within 2 days. MAIN FINDINGS: Glasgow Coma Scale (P = .001) scores in the early group were higher than those in the delayed group. The estimated time from ingestion to admission (P < .0001), creatine kinase level (P < .01), number of cases demonstrating shock (P < .05), shock index (P < .0001), and heart rate (P = .001) in the early group were smaller than those in the delayed group. Two subjects in the delayed group died of pneumonia and pulmonary embolism. PRINCIPAL CONCLUSIONS: Delayed arrival from ingestion, a low level of unconsciousness, and a sign of circulatory insufficiency in a patient with a psychotropic drug overdose were risk factors of a delayed recovery and death. PMID- 17870478 TI - Needs assessment: are Disaster Medical Assistance Teams up for the challenge of a pediatric disaster? AB - Pediatric patients are likely victims in a disaster and are more vulnerable in a disaster than adults, yet they have been essentially overlooked in disaster management according to the Pediatric Institute of Medicine Report. We did a needs assessment of Disaster Medical Assistance Teams regarding pediatric issues. Results were as follows: pediatric patients comprise a significant percentage of disaster victims (up to 85% in one disaster), and deficiencies were noted in the curriculum/training/resources. The percentage of time pediatric topics were missing from the curriculum was as follows: airway, 16%; trauma, 33%; disaster triage, 36%; burns, 42%; pain management, 42%; mental health, 45%; patient scenarios, 45%. The percentage of time pediatric equipment was missing was as follows: airway, 16%; intravenous lines, 37%; cervical collars, 38%; medicines, 38%; Broselow tape, 46%; backboards, 62%. Pediatric patients were included in disaster drills 63% of the time. Only 33% had pediatric protocols other than JumpSTART. A need to improve the pediatric components of Disaster Medical Assistance Teams was identified. PMID- 17870479 TI - Value of ischemia-modified albumin in the diagnosis of pulmonary embolism. AB - BACKGROUND: Pulmonary embolism (PE) is a common condition, but the diagnostic strategy for the evaluation of suspected PE is somewhat controversial. Despite the use of various biochemical markers (such as D-dimer and C-reactive protein) and various probability calculation algorithms based on clinical findings for that purpose, there is still a need for more specific and practical markers in PE diagnosis. The aim of this study was to investigate the diagnostic value of ischemia-modified albumin (IMA) levels in the diagnosis of PE. METHODS: This case control study was performed in the emergency department between March and September 2006. The serum IMA levels of a total of 60 individuals, consisting of 30 PE patients who had been definitively diagnosed via spiral computed tomographic angiography and 30 healthy volunteers, were examined. RESULTS: The measurement of IMA levels in patient plasma yielded mean values of 0.724 +/- 0.122 absorbance unit (ABSU) in the PE group and 0.360 +/- 0.090 ABSU in the control group. When plasma IMA levels in the PE group were compared with those in the control group, statistically significant increases in IMA were observed in the former (t = 13.19, df = 56, P < .0005). The value of 0.540 ABSU was calculated as the upper limit of reference interval. In the PE group, 97.7% (n = 29) had values exceeding 0.540 ABSU; none of the control subjects had values exceeding this cutoff value. CONCLUSIONS: In conclusion, our data suggest that IMA levels may be useful as a discriminative marker to exclude pulmonary embolism. PMID- 17870480 TI - Risk scoring systems to predict need for clinical intervention for patients with nonvariceal upper gastrointestinal tract bleeding. AB - BACKGROUND: Several risk score systems are designed for triage patients with acute nonvariceal upper gastrointestinal bleeding (UGIB). Blatchford score, which relies on only clinical and laboratory data, is used to identify patients with acute UGIB who need clinical intervention (before endoscopy). Clinical Rockall score, which relies on only clinical variables, is used to identify patients with acute UGIB who have adverse outcome, such as death or recurrent bleeding. Complete Rockall score, which relies on clinical and endoscopic variables, is also used to identify patients with acute UGIB who died or have recurrent bleeding. In our study, we define patients who need clinical intervention (ie, blood transfusion, endoscopic or surgical management for bleeding control) as high-risk patients. Our study aims to compare Blatchford score with clinical Rockall score and complete Rockall score in their utilities in identifying high risk cases in patients with acute nonvariceal UGIB. METHODS: International Classification of Diseases, Ninth Revision, Clinical Modification codes for admission diagnosis were used to recognize a cohort of patients (N = 354) with acute UGIB admitted to a tertiary care, university-affiliated hospital. Medical record data were abstracted by 1 research assistant blinded to the study purpose. Blatchford and Rockall scores were calculated for each enrolled patient. High risk was defined as a Blatchford score of greater than 0, a clinical Rockall score of greater than 0, and a complete Rockall score of greater than 2. Patients were defined as needing clinical intervention if they had a blood transfusion or any operative or endoscopic intervention to control their bleeding. Such patients were defined as high-risk patients. RESULTS: The Blatchford score identified 326 (92.1%) of the 354 patients as those with high risk for clinical intervention (ie, blood transfusion, endoscopic or surgical management for bleeding control). The clinical Rockall score identified 289 (81.6%) of the 354 patients as high risk, and the complete Rockall score identified 248 (70.1%) of the 354 patients as high-risk. The yield of identifying high-risk cases with the Blatchford score was significantly greater than with the clinical Rockall score (P < .0001) or with the complete Rockall score (P < .0001). In our total 354 patients, 246 (69.5%) patients were categorized as those with high risk for clinical intervention (ie, blood transfusion, endoscopic or surgical management for bleeding control, as aforementioned) in our study. The Blatchford score identified 245 (99.6%) of 246 patients as high-risk. Only 1 patient who met the study definition of needing clinical intervention was not identified via Blatchford score. This patient did not have recurrent bleeding nor die and did not receive blood transfusion. The clinical Rockall score identified 222 (90.2%) of 246 patients as high-risk. Twenty-four patients who met the study definition of needing clinical intervention were not recognized via clinical Rockall score. Of these patients, 0 died, 7 developed recurrent bleeding, and 6 needed blood transfusion. The complete Rockall score identified 224 (91.1%) of 246 patients as high-risk. Twenty-two patients who met the study definition of needing clinical intervention were not recognized via complete Rockall score. Of these patients, 2 died, 3 developed recurrent bleeding, and 20 needed blood transfusion. CONCLUSIONS: The Blatchford score, which is based on clinical and laboratory variables, may be a useful risk stratification tool in detecting which patients need clinical intervention in patients with acute nonvariceal UGIB. It does not need urgent endoscopy for scoring and has higher sensitivity than the clinical Rockall score and the complete Rockall score in identifying high-risk patients. PMID- 17870481 TI - Impact of conducted electrical weapons in a mentally ill population: a brief report. AB - INTRODUCTION: Conducted electrical weapons (CEWs) are used by some law enforcement agencies to subdue mentally ill subjects who are combative, violent, or suicidal. The use of CEWs in this population is controversial. Proponents advocate CEW use to avoid other forms of escalated force. Opponents advocate against CEW use because of the potential for abuse. What is lacking in the medical literature is documentation of the impact on outcome that this technology may have when used in this population. This project represents an initial report in this area. METHODS: A database of CEW use has been maintained since 1999 to which law enforcement agencies voluntarily report. This database was reviewed for occurrences of CEW use on mentally ill and suicidal subjects. Situation outcome and potential for law enforcement use of deadly force as an alternative were recorded. Data analysis was performed using descriptive statistics. RESULTS: There were 10,608 reports of CEW use over a 72-month period. Of these, there were 2452 uses on mentally ill subjects; and of these, 1111 (45.3%) were in situations where lethal force by the law enforcement agency would have been justified or where the subject represented an imminent life threat to himself. CONCLUSION: The mentally ill represents a significant portion of subjects upon whom CEWs are used. These data suggest frequent use of CEWs in situations where deadly force would otherwise be justified and in situations where subjects exhibit imminent danger to themselves. These data also suggest that escalation to deadly force was avoided in many mental illness and suicidal situations by the presence of a CEW. PMID- 17870482 TI - A new cardiopulmonary resuscitation method using only rhythmic abdominal compression: a preliminary report. AB - This article introduces 2 new cardiopulmonary resuscitation (CPR) concepts: (1) the use of only rhythmic abdominal compression (OAC) to produce blood flow during CPR with ventricular fibrillation and (2) a new way of describing coronary perfusion effectiveness, namely, the area between the aortic and right atrial pressure curves, summed over 1 minute, the units being millimeters of mercury per second. We call this unit the coronary perfusion index (CPI). True mean coronary perfusion pressure is CPI/60. We also relate CPI during CPR with ventricular fibrillation to the CPI for the normally beating heart in the same animal, obtained before each experiment. This 11-pig (25-35 kg) study compares the CPI for standard chest-compression CPR and that obtained with OAC-CPR. The coronary perfusion ratio for OAC-CPR compared with standard chest-compression CPR was 1.6 +/- 0.73 (P = .024). In other words, OAC-CPR produced 60% more coronary perfusion than standard chest-compression CPR, with no damage to visceral organs. PMID- 17870483 TI - Use of a triage pain protocol in the ED. AB - PURPOSES: This study was designed to evaluate the ability of a triage pain protocol to improve frequency and time to delivery of analgesia for musculoskeletal injuries in the emergency department (ED). BASIC PROCEDURES: Frequency and time to analgesic administration were measured before and after use of a triage pain protocol. The protocol allowed analgesic medications to be given at the time of triage. MAIN FINDINGS: Time to medication administration was 76 minutes (95% confidence interval [CI], 68-84 minutes) before and 40 minutes (95% CI, 32-47 minutes) after the protocol. Five hundred fifty-nine (70%) of 800 patients received analgesics using the protocol compared with 212 of 471 (45%) patients prior. PRINCIPAL CONCLUSIONS: Use of a triage pain protocol increased the number of patients with musculoskeletal injury who received pain medication in the ED. Use of the protocol also resulted in a decrease in the time to analgesic medication administration. PMID- 17870484 TI - Identifying high-risk patients for triage and resource allocation in the ED. AB - Five-point triage assessment scales currently used in many emergency departments (EDs) across the country have been shown to be accurate and reliable. We have found the system to be highly predictive of outcome (hospital admission, intensive care unit/operating room admission, or death) at either extreme of the scale but much less predictive in the middle triage group. This is problematic because the middle triage acuity group is the largest, in our experience comprising almost half of all patients. Patients triaged to the 2 highest acuity categories (A and B) have admission/ED death rates of 76% and 43%, respectively. In contrast, the 2 lowest acuity categories (D and E) have admission/ED death rates of 1% or less. The middle category (C), however, has an overall admission/ED death rate of 10%, too high to be comfortable with prolonged delays in the ED evaluation of these patients. We studied this group to determine if easily obtainable clinical factors could identify higher-risk patients in this heterogeneous category. Data were obtained from a retrospective, cross-sectional study of all patients seen in 2001 at an urban academic hospital ED. The main outcome measure for multivariate logistic regression models was hospital admission among patients triaged as acuity C. Acuity C patients who were 65 years or older, presenting with weakness or dizziness, shortness of breath, abdominal pain, or a final diagnosis related group diagnosis of psychosis, were more likely to be admitted than patients originally triaged in category B. These findings suggest that a few easily obtainable clinical factors may significantly improve the accuracy of triage and resource allocation among patients assigned with a middle-acuity score. PMID- 17870485 TI - The management of severe toxic alcohol ingestions at a tertiary care center after the introduction of fomepizole. AB - INTRODUCTION: Ethylene glycol and methanol ingestions are relatively uncommon but potentially lethal poisonings. Recent trials have demonstrated that fomepizole effectively blocks alcohol dehydrogenase (ADH) in toxic alcohol overdoses, and may eliminate the need for emergent hemodialysis and intensive care unit admission. However, controversy remains in the role of fomepizole in clinical practice. The purpose of this study was to describe the presentation, management and clinical course of toxic alcohol ingestions at a tertiary care referral center after the introduction of fomepizole to hospital formulary. METHODS: Data was collected on all patents treated for toxic alcohol ingestions for a 1-year period in a tertiary care referral center. Patients who received fomepizole or ethanol infusions, or who underwent hemodialysis were identified by ED, pharmacy, hemodialysis and ICU databases. The patients' medical records were reviewed, and data was recorded on a predetermined computerized data collection form. RESULTS: Overall, twenty (20) toxic ingestions (14 methanol; 6 ethylene glycol) were identified over the one year period. Fomepizole was used for ADH blockade in 12/20 cases; ETOH infusions in 15/20 cases (combined ETOH and fomepizole use in 7/20). The majority of toxic alcohol exposures were admitted to an intensive care unit (19/20) and received emergent hemodialysis (19/20). All patients were discharged from hospital alive. CONCLUSIONS: Patients with methanol and ethylene glycol ingestions who presented to our centers had significant toxicity and received both HD and ICU admission. Further research is required to determined if the method of ADH blockade affects the need for hemodialysis or ICU admission in toxic alcohol ingestions. PMID- 17870486 TI - Inappropriate prescribing in an older ED population. AB - The objective of this study was to determine the prevalence of potentially inappropriate medication (PIMs) use in older emergency department (ED) patients based on the updated 2002 Beers criteria. This was a retrospective analysis of 352 consecutive ED visits by patients aged 65 years and older. The mean number of medications taken was 8.4 per patient. In the study population, 111 (32%; 95% confidence interval [CI], 27-36) of 352 patients were taking at least 1 PIM at ED presentation. Propoxyphene/acetaminophen (24/352, 7%; 95% CI, 4-10), muscle relaxants (14/352, 4%; 95% CI, 2-7), and antihistamines (12/352, 3%; 95% CI, 2-6) were the most common PIMs. Among 101 of 193 patients discharged home from the ED with a new prescription, 13 (13%; 95% CI, 6-19) were also given PIMs. The most common PIMs were propoxyphene/acetaminophen (3/101; 95% CI, 1-8), diazepam (3/101; 95% CI, 1-8), cyclobenzaprine (2/101, 2%; 95% CI, 0-7), and diphenhydramine (2/101, 2%; 95% CI, 0-7). Outpatient PIM use in older ED patients is highly prevalent. Further education is needed regarding prescribing practices in this population group. PMID- 17870487 TI - Does vaccinating ED health care workers against influenza reduce sickness absenteeism? AB - This study aims to investigate the association between influenza vaccination of health care workers (HCWs) and sickness absenteeism. A retrospective cohort study was conducted in an emergency department (ED) of an acute care hospital. All full time HCWs except physicians (73 nurses and health care attendants) were included. Influenza vaccine was administered to HCWs on a voluntary basis commencing November 2004. Absenteeism due to influenza-like illness during the period from January to October 2005 was noted. The mean number of cumulative sick leave days per person was smaller (1.0 days against 1.75 days) in vaccine recipients than in vaccine nonrecipients although the difference was not statistically significant. A significantly larger proportion of subjects took sick leave because of influenza-like illness in the vaccine nonrecipient group (55% against 30.3%, P = .034). CONCLUSION: Influenza vaccination of HCWs in the ED setting is significantly associated with a fewer number of HCWs requiring sick leave. PMID- 17870488 TI - Care of the pacemaker/implantable cardioverter defibrillator patient in the ED. AB - As the population ages and the prevalence of cardiovascular disease increases, patients with pacemakers and implantable cardioverter defibrillators (ICDs) more commonly present to the emergency department. These patients can have complex medical issues related to and independent of their pacemaker/ICD that require careful management by the emergency physician. This article will review the major diagnostic and therapeutic considerations in the emergency care of patients with pacemakers and ICDs. PMID- 17870489 TI - Clinician vs mathematical statistical models: which is better at predicting an abnormal chest radiograph finding in injured patients? AB - OBJECTIVE: The purpose of this study was to determine if statistical models for prediction of chest injuries would outperform the clinician's (MD) ability to identify injured patients at risk for a thoracic injury diagnosed by chest radiograph (CXR). DESIGN: A prospective observational study was done during a 12 month period. SETTING: The study was conducted in a level I trauma center. PATIENTS: Injured patients meeting trauma team activation criteria were enrolled to the study. INTERVENTIONS: Physical examination findings by a clinician were interpreted and CXR was performed. OUTCOME MEASURES: The accuracy of 2 mathematical models is compared against the accuracy of clinician's clinical judgment in predicting an injury by CXR. Two newly constructed multivariate models, binary logistic regression (LR) and classification and regression tree (CaRT) analysis, are compared to previously published data of clinician clinical assessment of probability of thoracic injury identified by CXR. RESULTS: Data for 757 patients were analyzed. Classification and regression tree analysis developed a stepwise decision tree to determine which signs/symptoms were indicative of an abnormal CXR finding. The sensitivity (CaRT, 36.6%; LR, 36.3%; MD, 58.7%), specificity (CaRT, 98.3%; LR, 98.2%; MD, 96.4%), and error rates (CaRT, 0.93; LR, 0.94; MD, 0.82) show that the mathematical decision aids are less sensitive and risk more misclassification compared to clinician judgment in predicting an injury by CXR. CONCLUSION: Clinician judgment was superior to mathematical decision aids for predicting an abnormal CXR finding in injured patients with chest trauma. PMID- 17870490 TI - When the heart remembers. AB - We present a 61-year-old patient who showed deep T wave inversion on her electrocardiogram (ECG) after cardioversion of her atrial flutter to sinus rhythm. A cardiac catheterization showed normal coronary arteries. The T wave inversion on her ECG is thought to be due to a cardiac memory phenomenon. Cardiac memory is a phenomenon that appears with T wave inversion on ECG after a change in the activation sequence of the heart. It may mimic cardiac ischemia and may mask any condition that appears with T wave abnormality on the ECG. PMID- 17870491 TI - Ophthalmic diagnoses in the ED: optic neuritis. AB - Optic neuritis is the most common cause of decreased vision due to optic nerve dysfunction in patients who are 20 to 40 years of age. Optic neuritis, or inflammation of the optic nerve, is primarily due to idiopathic demyelination. Demyelinative lesions seen in optic neuritis are not unlike those seen in plaque associated with multiple sclerosis. In fact, acute inflammatory demyelination of the optic nerve commonly occurs as an initial manifestation of multiple sclerosis. Key features of optic neuritis include a vision loss occurring over 1 to 10 days, color vision impairment, eye pain with motility, and an afferent pupillary defect. This significant diagnosis can be challenging to an emergency physician as it is relatively infrequently observed. PMID- 17870492 TI - Recognition of pneumoperitoneum using bedside ultrasound in critically ill patients presenting with acute abdominal pain. AB - Bedside ultrasound examinations performed by emergency physicians are goal directed studies meant to answer specific questions. These studies are frequently performed in critically ill patients with undifferentiated abdominal pain who are suspected of having intra-abdominal hemorrhage or a ruptured abdominal aortic aneurysm. Patients presenting with a perforated hollow viscus may have a similar clinical presentation. Although detection of the sonographic findings associated with a perforated hollow viscus is not a current study goal, these findings may be readily apparent during the performance of examinations to detect an abdominal aortic aneurysm or intra-abdominal hemorrhage. Therefore, it is imperative that emergency physicians be familiar with the sonographic findings associated with a perforated hollow viscus. Three illustrative cases are presented with a review of sonographic findings. PMID- 17870493 TI - Fentanyl in the prehospital setting. PMID- 17870494 TI - Severe neuropsychiatric manifestations and rhabdomyolysis in a patient with imidacloprid poisoning. PMID- 17870495 TI - PiCCO monitoring accuracy in low body temperature. PMID- 17870496 TI - The current status of the emergency medical system in Korea. PMID- 17870497 TI - Technetium Tc 99m methylene diphosphonate bone scintigraphy of rhabdomyolysis after near-drowning in cold seawater. PMID- 17870498 TI - The Alvarado score and antibiotics therapy as a corporate protocol versus conventional clinical management: randomized controlled pilot study of approach to acute appendicitis. PMID- 17870499 TI - The relationship of air pollution to ED visits for asthma differs between children and adults. PMID- 17870500 TI - Electrocardiographic prediction of acute left main coronary artery occlusion. PMID- 17870501 TI - The authors respond: Methadone overdose. PMID- 17870502 TI - A clinical score predicting the need for hospitalization in scorpion envenomation. PMID- 17870503 TI - Cardiac tamponade caused by a leaking coronary saphenous vein graft aneurysm. PMID- 17870504 TI - Extensive anterolateral myocardial infarction caused by left main coronary artery dissection after blunt chest trauma: a case report. PMID- 17870505 TI - Hyperacute T wave, the early sign of myocardial infarction. PMID- 17870506 TI - Identification of false-positive creatine kinase-MB activity in a patient with nonketotic hyperglycemia. PMID- 17870507 TI - Considerations in the diagnosis and therapy for deep vein thrombosis. PMID- 17870508 TI - Diaphragmatic embolism after endoscopic injection sclerotherapy for gastric variceal bleeding. PMID- 17870509 TI - Thyroid storm precipitated by organophosphate intoxication. PMID- 17870510 TI - Purple urine bag syndrome in a dead-on-arrival patient: case report and articles reviews. PMID- 17870511 TI - Perforation of isolated jejunum after a blunt trauma: case report and review of the literature. PMID- 17870512 TI - Eosinophilic pneumonia associated with foot injury from a sea urchin. PMID- 17870513 TI - Continuous low-dose infusion of terlipressin as a rescue therapy in meningococcal septic shock. PMID- 17870514 TI - Right ventricular endocardial tumor mimicking acute massive pulmonary embolism. PMID- 17870515 TI - Pseudoseptic arthritis after accidental intra-articular deposition of the pneumococcal polyvalent vaccine: a case report. PMID- 17870516 TI - Ultrasonography diagnosis of superior mesenteric artery syndrome in the ED. PMID- 17870517 TI - Clinical epidemiology of breast cancer in the elderly. AB - Breast cancer will increasingly become a disease affecting the lives of older women, especially in more developed countries, the prevalence rising up to 7% over age 70 in the near future. A review of the population-based literature and an analysis of the data of the Eindhoven Cancer Registry and European data regarding the diagnosis, treatment and prognosis showed that the proportion with unstaged and advanced disease (stages III and IV) is higher among elderly patients compared to younger ones and that their treatment is generally less aggressive, although the proportion receiving chemotherapy is increasing since the early 1990s. Disease specific (or relative) survival of elderly breast cancer patients is generally lower and the prevalence of serious (life expectancy affecting) co-morbidity is higher (>50% in patients over age 70). Because of large individual variations in physical and mental conditions, limited evidence from RCTs and personal preferences prevailing in the decision-making process, treatment of older breast cancer patients seems difficult to fit into guidelines. Therefore, alternative research strategies are needed to understand and improve the care for the elderly breast cancer population, such as descriptive (registry based) studies and a qualitative, individual-based approach. PMID- 17870518 TI - DNA-repair and carcinogen-metabolising enzymes genetic polymorphisms as an independent risk factor for hepatocellular carcinoma in Caucasian liver transplanted patients. AB - We studied polymorphisms of three genes, UDP-glucuronosyltransferase1A7 (UGT1A7), Glutathione-S-transferaseM1 (GSTM1) and X-Ray Cross Complementing group 1 (XRCC1), involved in detoxification of xenobiotics or DNA-repair in a population of 133 liver-transplanted patients, including 56 patients with hepatocellular carcinoma (HCC) and 77 without HCC, and in 89 healthy controls originating from the south of France. Multiple logistic regression analysis showed that, among liver-transplanted patients, interactions between XRCC1-G/G or -G/A and GSTM1-nul polymorphisms were independently associated with hepatocellular carcinoma (p interaction=0.027) concurrently with increasing age (p<0.001), male sex (p=0.037) and chronic hepatitis B or C virus infection (p=0.018 and p=0.001 respectively). On the contrary, no relationship was observed between UGT1A7 polymorphisms considered alone or in interaction with GSTM1 or XRCC1 polymorphisms and HCC. This suggests that concomitant impaired metabolism of carcinogenic compounds and impaired DNA-repair function play an important role in liver carcinogenesis in high-risk cirrhotic patients originating from the south of France. PMID- 17870519 TI - Step by step development of clinical care pathways for older cancer patients: necessary or desirable? AB - Medical and nursing staff in oncology for older cancer patients are confronted with a range of problems including co-morbidity, poly-pharmacy, cognitive impairments, emotional problems, functional limitations, sensory impairment and a lack of social support. Comprehensive geriatric assessment identifies many of the existing problems and can be used to estimate life expectancy and tolerance of treatment. However, health care providers have to interpret and apply the medical and nursing information and must deal with specific problems and care needs throughout the continuum of cancer care. Imperfect interdisciplinary communication, cooperation and patient-provider communication may further complicate the care actually delivered. A clinical care pathway aims to improve continuity, increase multidisciplinary tuning and deliver appropriate patient education, treatment and care for vulnerable older cancer patients. This paper gives an overview of common problems in older cancer patients and addresses communication barriers through the development of clinical care pathways in geriatric oncology. PMID- 17870521 TI - Masers to magic bullets: an updated history of lasers in dermatology. AB - Laser therapy is one of the fastest expanding and most exciting fields in dermatology. From its theoretical beginnings in Einstein's imagination, lasers have come to be used in treatments for conditions ranging from skin malignancy and acne to hirsutism and photoaging. We will briefly review the evolution of laser treatment, with a focus on the recent developments surrounding the new millennium. PMID- 17870522 TI - Lasers and light sources for the removal of unwanted hair. AB - The long-term removal of unwanted hair has become one of the most common and popular cosmetic laser treatments being performed around the world. This manuscript will review a variety of lasers and light sources that have been and are currently being used for epilation of the skin. All of the lasers and light systems currently available do work for long-term hair removal; it is the responsibility of the treating clinician to understand the varying technologies and what the limits of each device is and, most importantly, to be able to handle any untoward effects that might arise during the coarse of treatment. Then, hair removal can be successful for both the patient and the physician using their particular medical device. PMID- 17870523 TI - Laser therapy for leg veins. AB - Visible veins on the leg are a common cosmetic concern affecting approximately 80% of women in the United States (Engel A, Johnson MI, Haynes SG. Health effects of sunlight exposure in the United States: results from the first national health and nutrition examination survey, 1971-1974. Arch Dermatol 1988;124:72-9). Without a quick and noninvasive treatment available, leg veins present a therapeutic challenge. This challenge has been tackled by the design of lasers with longer pulse durations, and the use of lasers with longer wavelengths and cooling devices. Recent studies show the efficacy of laser treatment beginning to approach that of sclerotherapy, the gold standard. This review outlines the principles guiding laser treatment, the current available options, and a clinically oriented approach to treating leg veins. PMID- 17870524 TI - Ablative laser resurfacing: high-energy pulsed carbon dioxide and erbium:yttrium aluminum-garnet. AB - The development of the short-pulsed high-energy carbon dioxide laser in the mid 1990's led to the emergence of laser skin resurfacing. Used in the continuous mode, the CO(2) laser can cut and coagulate simultaneously. Used in the pulsed mode, the CO(2) laser is a powerful tool for epidermal ablation in many different contexts both therapeutic and cosmetic. Both the CO(2) and Erbium YAG lasers emit light in the infrared spectrum. Energy is preferentially absorbed by intracellular water creating rapid heating and vaporization of tissue. Because of the wavelength of the Er:YAG laser (2940 nm) more closely approximates the absorption peak of water (3000 nm) the target chromophore than the CO(2) laser (10,600 nm) nearly all of the energy is absorbed in the epidermis and papillary dermis yielding superficial ablation and less underlying thermal damage. The advantages, disadvantages, and applications of each type of laser resurfacing will be discussed. Despite proven efficacy, the public acceptance of laser resurfacing has declined with the emergence of new laser systems that cause dermal remodeling without ablating the overlying epidermis dramatically reducing recovery time. In the absence of blinded comparison studies, it remains unclear whether the clinical results of the newer 'nonablative' laser systems compare with their ablative predecessors. PMID- 17870525 TI - Nonablative tissue remodeling and photorejuvenation. AB - Nonablative facial resurfacing is a noninvasive approach to tissue remodeling and skin rejuvenation. These procedures are considered an alternative to the more traditional laser resurfacing with less dramatic effects, but also with significantly less downtime. Results vary based on the lasers and light sources used. In general, the infrared lasers improve texture, visible light lasers somewhat improve texture but greatly reduce redness and telangiectasias, and intense pulsed light devices improve both red targets and brown discoloration, as well as skin texture. Lastly, low-energy devices may improve redness and texture modestly. Patient selection, as well as device selection, is based on the outcome desired. Side effects are uncommon and preventable. PMID- 17870526 TI - Fractional resurfacing. AB - Fractional resurfacing produces a distinctive thermal damage pattern by creating discrete columns of thermal damage referred to as microthermal treatment zones. It characteristically spares the tissue surrounding each microthermal treatment zone leading to fast epidermal repair. Fractional resurfacing has been successfully used in treating a variety of skin conditions including melasma, dyschromia, lentigenes, wrinkles, and acne scars with minimal downtime. It is safer to use off the face and in darker skin types. PMID- 17870528 TI - In pursuit of defining clinical relevance of positive patch tests results. AB - According to the current classification of clinical relevance of the positive patch test reactions, the positive results of patients who are allergic to various allergens that are not responsible for the present dermatitis do not fit into the category of "relevant to present dermatitis" but should be defined as "relevant to a preceding bout of dermatitis." This seems to us inappropriate and misleading because reexposure to the sensitizing agent would quickly revert their reaction to "relevant to present dermatitis." We suggest an alternative possibility to the current division of the various types of clinical relevance, namely, "relevance to a present allergy other than the presenting dermatitis." PMID- 17870527 TI - Nonablative cutaneous remodeling using radiofrequency devices. AB - In recent years, several new radiofrequency devices have been introduced for treatment of a variety of skin conditions, particularly, skin wrinkling and laxity. These nonsurgical systems induce tissue tightening and contour changes through dermal collagen remodeling without disruption of the overlying epidermis, obviating a significant recovery period or risk of serious adverse sequelae. As such, radiofrequency-based systems have been used successfully for nonablative skin rejuvenation, atrophic scar revision, and treatment of unwanted hair, vascular lesions, and inflammatory acne. PMID- 17870529 TI - Cobo and her friends: the caring clowns. PMID- 17870531 TI - Synthesis of novel anilinoquinolines as c-fms inhibitors. AB - A novel series of potent substituted anilinoquinolines were discovered as c-fms inhibitors. The potency could be manipulated upon modification of the C4 aniline and C7 aryl functionality. Pharmacokinetic analysis identified a metabolically stable analog suitable for further investigative work. PMID- 17870532 TI - Novel heparin/heparan sulfate mimics as inhibitors of HGF/SF-induced MET activation. AB - The synthesis of simple, non-sugar glycosaminoglycan (GAG) mimics has been achieved and the analogues evaluated for their ability to inhibit the activation of the MET receptor by hepatocyte growth factor/scatter factor (HGF/SF). PMID- 17870533 TI - Arene cis-dihydrodiols: useful precursors for the preparation of analogues of the anti-tumour agent, 2-crotonyloxymethyl-(4R,5R,6R)-4,5,6-trihydroxycyclohex-2 enone (COTC). AB - The synthesis of 6-epi-COTC, a diastereoisomer of Streptomyces metabolite 2 crotonyloxymethyl-(4R,5R,6R)-4,5,6-trihydroxycyclohex-2-enone (COTC), is described. The anti-cancer activities of the novel analogue, in racemic and enantiomerically pure forms, are presented. PMID- 17870534 TI - Two new phenylpiperazines with atypical antipsychotic potential. AB - Two new series of substituted arylpiperazines with heterocyclic 3-propoxy benzimidazole or 3-propoxy-benzimidazole-2-thione groups were synthesized and their in vitro binding affinities for the D(2), 5-HT(1A), 5-HT(2A), and alpha(1) adrenergic receptors determined. Among them, only two compounds with phenyl aryl constituent (8a and 9a) showed 5-HT(2A)/D(2) pK(i) binding ratios proposed for atypical neuroleptics. As to their behavioral screening on rodents, both compounds exhibited a non-cataleptic action in rats and antagonized D-amphetamine induced hyperlocomotion in mice, suggesting their possible atypical antipsychotic potency. PMID- 17870535 TI - Nipple sparing mastectomy: an innovative skin incision for an alternative approach. AB - Choice of the most appropriate surgical treatment for breast cancer patients can also be a technical issue. Cosmetic results after conservative surgery can be poor in certain instances and, at the same time, total mastectomy can appear as an over-treatment. For some selected patients, the "nipple sparing mastectomy" (NSM) is an alternative surgical treatment and more and more papers on this technique are appearing in the literature. One hundred and two NSMs have been performed in our department between June 2003 and October 2006, initially via periareolar skin incision, now through a skin incision on the lateral aspect of the breast to reduce the necrotic risk for the nipple. The lateral skin incision saves the integrity of skin blood supply, allows for a complete breast gland removal and saves the integrity of the body image of women who show no scars when seen upfront. PMID- 17870536 TI - Validation of an automated procedure for the prediction of relative free energies of binding on a set of aldose reductase inhibitors. AB - Among the available methods for predicting free energies of binding of ligands to a protein, the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and molecular mechanics generalized Born surface area (MM-GBSA) approaches have been validated for a relatively limited number of targets and compounds in the training set. Here, we report the results of an extensive study on a series of 28 inhibitors of aldose reductase with experimentally determined crystal structures and inhibitory activities, in which we evaluate the ability of MM-PBSA and MM GBSA methods in predicting binding free energies using a number of different simulation conditions. While none of the methods proved able to predict absolute free energies of binding in quantitative agreement with the experimental values, calculated and experimental free energies of binding were significantly correlated. Comparing the predicted and experimental DeltaG of binding, MM-PBSA proved to perform better than MM-GBSA, and within the MM-PBSA methods, the PBSA of Amber performed similarly to Delphi. In particular, significant relationships between experimental and computed free energies of binding were obtained using Amber PBSA and structures minimized with a distance-dependent dielectric function. Importantly, while free energy predictions are usually made on large collections of equilibrated structures sampled during molecular dynamics in water, we have found that a single minimized structure is a reasonable approximation if relative free energies of binding are to be calculated. This finding is particularly relevant, considering that the generation of equilibrated MD ensembles and the subsequent free energy analysis on multiple snapshots is computationally intensive, while the generation and analysis of a single minimized structure of a protein-ligand complex is relatively fast, and therefore suited for high-throughput virtual screening studies. At this aim, we have developed an automated workflow that integrates all the necessary steps required to generate structures and calculate free energies of binding. The procedure is relatively fast and able to screen automatically and iteratively molecules contained in databases and libraries of compounds. Taken altogether, our results suggest that the workflow can be a valuable tool for ligand identification and optimization, being able to automatically and efficiently refine docking poses, which sometimes may not be accurate, and rank the compounds based on more accurate scoring functions. PMID- 17870537 TI - Synthesis of some tropane derivatives of anticipated activity on the reuptake of norepinephrine and/or serotonin. AB - A variety of tropane derivatives 14a-g were prepared via the reaction of the alcohol analogs 12a and 12b with substituted fluorobenzenes 13a-f. The prepared compounds were tested for their activity and selectivity toward the norepinephrine transporter (NET) and serotonin transporter (SERT) using yohimbine induced mortality and 5-hydroxytryptophan-induced neurotoxicity in mice, respectively. All the tested compounds were found to be NE and 5-HT reuptake inhibitors except 14d which exhibited selective 5-HT reuptake inhibition activity. PMID- 17870538 TI - A novel QSAR model for prediction of apoptosis-inducing activity of 4-aryl-4-H chromenes based on support vector machine. AB - In this work some chemometrics methods were applied for modeling and prediction of the induction of apoptosis by 4-aryl-4-H-chromenes with descriptors calculated from the molecular structure alone. The genetic algorithm (GA) and stepwise multiple linear regression methods were used to select descriptors which are responsible for the apoptosis-inducing activity of these compounds. Then support vector machine (SVM), artificial neural network (ANN), and multiple linear regression (MLR) were utilized to construct the nonlinear and linear quantitative structure-activity relationship models. The obtained results using SVM were compared with ANN and MLR; it revealed that the GA-SVM model was much better than other models. The root-mean-square errors of the training set and the test set for GA-SVM model are 0.181, 0.241 and the correlation coefficients were 0.950, 0.924, respectively, and the obtained statistical parameters of cross validation test on GA-SVM model were Q(2)=0.71 and SRESS=0.345 which revealed the reliability of this model. The results were also compared with previous published model and indicate the superiority of the present GA-SVM model. PMID- 17870539 TI - Discovery of 1,1-dioxo-1,2,6-thiadiazine-5-carboxamide derivatives as cannabinoid like molecules with agonist and antagonist activity. AB - A series of new 2-substituted 1,1-dioxo-1,2,6-thiadiazine-5-carboxylate derivatives have been prepared from monosubstituted sulfamides in order to obtain N-substituted 1,1-dioxo-1,2,6-thiadiazine-5-carboxamides as novel cannabinoid derivatives, analogues of Rimonabant (SR141716A). Their potential functional activity on cannabinoid receptors has been evaluated in vitro and in vivo in mice, showing that two compounds (37 and 39) behave as cannabinoid agonists in vitro. Their potency is lower than that of the reference compound, WIN 55,212-2, but their efficacy is similar to that of this cannabinoid agonist, although no in vivo activity is observed. Another derivative (38) behaves as a cannabinoid antagonist both in vitro and in vivo, being its efficacy and potency similar to that of the well-known antagonist SR141716A. PMID- 17870540 TI - Efficient one-pot synthesis of biologically active polysubstituted aromatic amines. AB - An efficient and modular one-pot synthesis of polysubstituted aromatic amines by a mild reductive amination procedure is described and the biological potential of these nitrogen-centered compounds is demonstrated by growth inhibition of murine connective tissue cells and microscopy-based morphological studies. PMID- 17870541 TI - Hologram QSAR model for the prediction of human oral bioavailability. AB - A drug intended for use in humans should have an ideal balance of pharmacokinetics and safety, as well as potency and selectivity. Unfavorable pharmacokinetics can negatively affect the clinical development of many otherwise promising drug candidates. A variety of in silico ADME (absorption, distribution, metabolism, and excretion) models are receiving increased attention due to a better appreciation that pharmacokinetic properties should be considered in early phases of the drug discovery process. Human oral bioavailability is an important pharmacokinetic property, which is directly related to the amount of drug available in the systemic circulation to exert pharmacological and therapeutic effects. In the present work, hologram quantitative structure-activity relationships (HQSAR) were performed on a training set of 250 structurally diverse molecules with known human oral bioavailability. The most significant HQSAR model (q(2)=0.70, r(2)=0.93) was obtained using atoms, bond, connection, and chirality as fragment distinction. The predictive ability of the model was evaluated by an external test set containing 52 molecules not included in the training set, and the predicted values were in good agreement with the experimental values. The HQSAR model should be useful for the design of new drug candidates having increased bioavailability as well as in the process of chemical library design, virtual screening, and high-throughput screening. PMID- 17870542 TI - Mimetics of the tri- and tetrasaccharide epitope of GQ1balpha as myelin associated glycoprotein (MAG) ligands. AB - The synthesis of phenoxyphenyl, phenoxybenzyl, biphenyl, and phenyltriazole substituted sialic acid derivatives as mimics of the tri- and tetrasaccharide epitopes of GQ1balpha is described. These synthetically easily available sialosides show comparable or even enhanced affinity to MAG compared with the natural tri- and tetrasaccharide epitopes and form a new class of potential MAG antagonists. PMID- 17870543 TI - Synthesis and antibacterial activity of pyranmycin derivatives with N-1 and O-6 modifications. AB - Continuing from our ongoing effort in modifying aminoglycoside antibiotics with the goal of counteracting drug resistant bacteria, we have further derivatized pyranmycin, a neomycin class aminoglycoside antibiotic, with modifications at O-6 and N-1 positions. The revealed SAR results demonstrated that the antibacterial activity of pyranmycin can be modulated by different acylic substituents at O-6. Among these results, the 6-O-aminoethyl derivative, JT050, showed effective activity against resistant strain Escherichia coli (pTZ19U-3) and E. coli (pSF815), which provides insight into further structural modifications. PMID- 17870544 TI - Additional level of information about complex interaction between non-nucleoside inhibitor and HIV-1 reverse transcriptase using biosensor-based thermodynamic analysis. AB - The thermodynamics of the interaction between mutant HIV-1 reverse transcriptase (K103N and Y181C) and a non-nucleoside reverse transcriptase inhibitor (NNRTI), the phenylethylthiazolylurea compound MIV-150, was obtained by determining the temperature dependence of the kinetic rate constants. Large entropic changes in the forward and backward steps of the isomerization between a non-binding competent and a binding competent conformation of the enzyme, as well as in the binding steps, implied the involvement of major structural rearrangements upon interaction with the inhibitor. Despite of the entropic character of the overall interaction, the equilibrium for the binding of inhibitor was found to be predominantly enthalpy-driven. The high affinity and the low affinity interactions of the heterogeneously interacting inhibitor showed different energetics in the analysis, revealing an expectedly higher enthalpic component for the high-affinity interaction. The thermodynamic profiles of the two enzyme variants displayed significant differences, which could not be derived from their kinetics at a single temperature. PMID- 17870545 TI - The design and synthesis of N-1-alkylated-5-aminoarylalkylsubstituted-6 methyluracils as potential non-nucleoside HIV-1 RT inhibitors. AB - Novel compounds 1a-u, which can be considered as hybrid analogues of MKC-442 and pyridinon, have been synthesized and evaluated as inhibitors of HIV-1 reverse transcriptase (HIV-1 RT). Starting from 6-methyluracil 2, 1-alkylated-5 bromomethyl-6-methyluracils 8 was prepared in four steps by hydroxymethylation, etherification, N-1 alkylation, and bromination. Finally, compounds 1a-u were achieved in the displacement of 5-bromomethyl group by nucleophiles with amino compounds. Some of compounds 1a-u showed potent inhibitory activity against HIV-1 RT. The most active compounds showed activity in the low micromolecular range with IC(50) values (IC(50) 0.82-5.09 microM) comparable to that of nevirapine (IC(50) 10.60 microM). The biological testing results are in accordance with the docking. PMID- 17870546 TI - Photomodulation of PS-modified oligonucleotides containing azobenzene substituent at pre-selected positions in phosphate backbone. AB - A new protocol has been developed for incorporation of a photoisomerizable azobenzene moiety into synthetic stereo-enriched [R(p)] and [S(p)] PS oligonucleotides. The azobenzene pendant is attached at pre-selected positions in internucleotidic phosphorothioate oligonucleotides of both [R(p)] and [S(p)] diastereomers using a novel reagent, N-iodoacetyl-p-aminoazobenzene, 1. The modified oligomers are purified on HPLC, characterized by LC-MS, and examined for their thermal and photoisomerization properties. The azobenzene moiety imparts greater stability to oligomer duplexes in (E) NN configuration as compared to (Z) configuration. The placement of the azobenzene pendant close to 5'-terminus (n-1) and 3'-terminus of the modified PS-oligos contributes maximum stability to the duplex while a gradual decline in stability occurs with azobenzene moving toward middle of the duplex. Circular Dichroism studies reveal that the chiral environment at the phosphorus center of the PS-oligos does not alter the global conformation of the DNA duplex as such, suggesting conservation of conformation of the modified DNA strands. PMID- 17870547 TI - Synthesis and biological evaluation of norcantharidin analogues: towards PP1 selectivity. AB - Simple modifications to the anhydride moiety of norcantharidin have lead to the development of a series of analogues displaying modest PP1 inhibition (low muM IC(50)s) comparable to that of norcantharidin (PP1 IC(50)=10.3+/-1.37 microM). However, unlike norcantharidin, which is a potent inhibitor of PP2A (IC(50)=2.69+/-1.37 microM), these analogues show reduced PP2A inhibitory action resulting in the development of selective PP1 inhibitory compounds. Data indicates that the introduction of two ortho-disposed substituents on an aromatic ring, or para-substituent favours PP1 inhibition over PP2A inhibition. Introduction of a p-morphilinoaniline substituent, 35, affords an inhibitor displaying PP1 IC(50)=6.5+/-2.3 microM; and PP2A IC(50)=7.9+/-0.82 microM (PP1/PP2A=0.82); and a 2,4,6-trimethylaniline, 23, displaying PP1 IC(50)=48+/-9; and PP2A IC(5) 85+/-3 microM (PP1/PP2A=0.56). The latter shows a 7-fold improvement in PP1 versus PP2A selectivity when compared with norcantharidin. Subsequent analysis of 23 and 35 as potential PP2B inhibitors revealed modest inhibition with IC(50)s of 89+/-6 and 42+/-3 microM, respectively, and returned with PP1/PP2B selectivities of 0.54 and 0.15. Thus, these analogues are the simplest and most selective PP1 inhibitors retaining potency reported to date. PMID- 17870548 TI - [Frequency of cardiovascular risk factors and co-morbidity in patients with rheumatic diseases]. AB - Analysis of national data from the health ministry programme of reduction of the cardiovascular risks (2002-2005) shows a high frequency of cardiovascular disease and cardiovascular risk factors in the general population. It is of interest to analyse these data in relation to the practice of rheumatology. In addition, the frequency of cardiovascular pathologies is higher in patients with rheumatoid arthritis and spondylarthropathy. These notions are also very important since these two populations are often treated with non-steroidal anti-inflammatory drugs for a long duration. General knowledge shown in this article concerning the cardiovascular risk factors and co-morbidities in the patients with rheumatic pathologies allows, within the context of a therapeutic decisional strategy in rheumatology, a better estimation of the individual benefit/risk ratio of each prescription and more particularly that of non-steroidal anti-inflammatory drugs. PMID- 17870549 TI - [What do we know about the cardiovascular toxicity of the NSAIDs?]. AB - Following the arterial thrombotic risk of rofecoxib (myocardial infarct and cerebral ischemic accidents) that led to its withdrawal from the market, the other coxibs then the NSAIDs have also been blacklisted. The factors responsible for the cardiovascular risk associated with the ingestion of the NSAIDs, selective or not, are not clearly identified. The objective of this review was to collect the available data from the literature, which would allow a better evaluation of the risk and its causes, principally on the basis of the results of randomised studies, but also of case reports and meta-analyses. There is an increase in the risk of arterial thrombotic events under coxibs and traditional NSAIDs, however the risk is variable in the both classes. The cardiovascular risk linked to celecoxib seems variable and modest, and at a standard dose and for usual treatment durations, the risk is probably inexistant. While the real risk of classical NSAIDs is difficult to appreciate from the available results, it can be concluded that the cardiovascular risk of naproxen is low. While part of the cardiovascular consequences of rofecoxib could be associated with increased arterial pressure, these effects are not exclusive to the coxibs since they have been observed with the conventional NSAIDs. However the increase in arterial pressure cannot probably explain everything. Similarly the cardiac insufficiency associated more particularly with rofecoxib, especially in some groups of patients (very old subjects) is not a new type of complication and does not seem to be more frequent with coxibs than with classical NSAIDs. No short-term arterial thrombotic risk of the coxibs and NSAIDs has been clearly demonstrated. PMID- 17870550 TI - [Are there any differences in the cardiovascular tolerance between classical NSAIDs and coxibs?]. AB - Three placebo-controlled studies have demonstrated deleterious cardiovascular (CV) effects of rofecoxib, celecoxib, and pare/valdecoxib. It remains to be determined whether this CV toxicity is specific to coxibs, or shared with all non steroidal anti-inflammatory drugs (NSAID). Seven meta-analyses show that, in comparison with non-specific NSAIDs, the risk of thrombotic CV accident is increased with rofecoxib and celecoxib, but not with valdecoxib or lumiracoxib. Concerning the risk of thrombotic CV accident, seven of the ten observational studies which have evaluated the risk, have found an increased risk for the non specific NSAID in comparison with non-exposed subjects,. The seven observational studies, which evaluated the risk of coxibs, have all found an increased risk with rofecoxib, and two with celecoxib. Three studies out of six have shown an increase of risk with rofecoxib and one study out of five with celecoxib. Two of the three studies, which have compared rofecoxib with celecoxib, have found an increased risk with rofecoxib. Concerning the risk of arterial hypertension, oedemas or congestive cardiac insufficiency, a meta-analysis and a randomised trial have shown a deleterious effect of rofecoxib in comparison with celecoxib and non-specific NSAID. Two studies have shown a deleterious effect of the non selective NSAID and three a deleterious effect of rofecoxib in comparison with non-exposed subjects. Three studies have demonstrated a deleterious effect of rofecoxib in comparison with non-specific NSAID. No study has shown any deleterious effect of celecoxib in comparison with subjects non-exposed or exposed to non-specific NSAID. These studies suggest that all the NSAID, specific or not, increase the CV and renal risk. This risk seems variable from a compound to another one and must be evaluated, for each patient, according to the susceptibility and associated risk factors. While waiting for other long-term controlled studies, the available data show the existence of a risk of CV secondary effect linked to the class of NSAID, specific (coxibs) or not. PMID- 17870551 TI - [How to evaluate the cardiovascular and renal risk at the individual level?]. AB - The cardiovascular impact of the non-steroidal anti-inflammatory drugs and the higher cardiovas-cular mortality during treatment of inflammatory rheumatism impose a rigorous evaluation of the cardiovascular risk of rheumatic patients. Large epidemiological studies have identified risk factors for cardiovascular diseases such as the age, male gender, family history (infarct, stroke), tobacco consumption, systolic arterial pressure, renal insufficiency, hypercholesterolemia, diabetes mellitis, sedentariness, obesity and "electric" ventricular hypertrophy. Some equations make it possible to evaluate the absolute cardiovascular risk at the individual level, which corresponds to the onset risk of a stroke in the 10 years to come in a subject according to the number and importance of each of his risk factors. It has been demonstrated that the correction of one or more risk factors reduce the overall cardiovascular risk, justifying the strategies for evaluating this risk to define therapeutic intervention thresholds. The impact of a long-term anti-inflammatory treatment or an inflammatory disease such as rheu-matoid arthritis has not been the subject of specific epidemiological study allowing these elements to be included in an equation of the estimation of the cardiovascular risk. However, the introduction of an anti-inflammatory treatment, likely to increase the cardiovascular risk of a patient, certainly justifies an evaluation of the absolute cardiovascular risk. PMID- 17870552 TI - [How to watch over a patient treated with a NSAID in relation to the cardiovascular and renal risk?]. AB - Despite the cardiovascular risk attributable to the NSAIDs, these drugs are among the most prescribed treatments in the world. Recently to manage this risk during chronic inflammatory rheumatisms a surveillance plan has been developed based on a decision algorithm. Given that the arterial thrombotic risks (myocardial or cerebral) are observed essentially during long-term treatments, two types of situation have been envisaged, short-term treatments and long-term treatments. Before any short-term NSAID prescription (less than one month), the cardio-renal risk should be evaluated. A pre-therapeutic check-up should include the search for risk factors and the treatment surveillance should imply a clinical and biological check-up carried out after 2 to 3 weeks of treatment. Before any long term NSAID prescription (more than one month), the arterial thrombotic risk (cardiac or cerebral) should be evaluated and the patient's history determined. Pre-therapeutic check-up and surveillance should be carried out and reconsidered at least every three months. In the case of high risk, the advice of a cardiologist should be obtained and drastic therapeutic measures taken. There are cases where the prescription of NSAIDs or coxibs is possibly not recommended. PMID- 17870553 TI - [What are the cardiovascular complications of the analgesics and glucocorticoids?]. AB - When prescribing a non-steroidal anti-inflammatory treatment but also an analgesic or a glucocorticoid, the cardiovascular risk of the patient should be assessed. The analgesics have few cardiovascular side effects and the main complications observed are linked essentially to the vagal action of the opioids. Acetaminophen is considered by several scientific societies to be the first line analgesic treatment, particularly in case of cardiovascular risk but with caution since cardiovascular toxicity of acetaminophen cannot be totally excluded. An overdose of dextropropoxyphene can result in cardiotoxicity. On the other hand, the glucocorticoids need to be prescribed cautiously, at the lowest possible dose and for the shortest possible duration due to the non-negligible cardiovascular risk, hypertension, dyslipidemia, hypokaliemia. PMID- 17870554 TI - [Are the NSAIDs able to compromising the cardio-preventive efficacy of aspirin?]. AB - OBJECTIVES: Some studies have recently suggested a potential pharmacodynamic interaction between aspirin and some non-selective non-steroidal anti inflammatory drugs (NSAIDs). We have evaluated the reality of this pharmacodynamic interaction and analyse its clinical pertinence. METHODS: Literature review (Medline search - December 2005). RESULTS: Several ex vivo studies show that some non-selective NSAIDs can block the active site of Cox1 thus preventing aspirin from exerting its platelet anti-aggregating cardio preventive action. Cox2 selective molecules do not act at this site. The few studies, mainly case reports, have analysed the potential loss of the cardiovascular preventive benefit of aspirin in patients receiving concomitantly non-selective anti-inflammatory drugs with controversial results. IN PRACTICE: It seems necessary to know the existence of this pharmacodynamic interaction between aspirin at a low dose and some non-selective anti-inflammatory drugs notably ibuprofen and naproxen. In the absence of a clear clinical demonstration, it is advisable to avoid the non-selective NSAIDs in patients treated with a low dose of aspirin. It might be advisable to switch to an anti-aggregating treatment other than aspirin (clopidrogel, etc.) in these cases. At the present time, however, there are no data on which to base such a recommendation. PMID- 17870555 TI - [What is the impact of cardiovascular and renal complications on the benefit/risk ratio of the NSAIDs?]. AB - Long-term studies of NSAIDs have demonstrated cardiovascular toxicity which poses a general problem of the benefit risk between the relief of the patient's symptoms and the risk of digestive and cardiovascular toxicity. The digestive complications and the risk factors associated with the ingestion of NSAIDs have been defined by numerous studies but the prevention of this digestive toxicity can be attempted. The benefit-risk ratio caused by the digestive and cardiovascular toxicities of the NSAIDs and COX-2 inhibitors must be evaluated for each individual before starting a treatment. For a treatment of short duration in patients with a low risk of digestive and cardiovascular complications, the risk of digestive toxicity must be taken into consideration first and the COX-2 inhibitors are favoured. For a treatment of long duration the risk must be evaluated with the greatest care. In the case of cardiovascular risk factors, the cardiovascular risk must be evaluated and the treatment must be prescribed at the lowest dose for the shortest duration. In patients with very high risk of digestive and cardiovascular complications, since the digestive and cardiovascular extra-mortality associated with the ingestion of NSAIDs or COX-2 inhibitors is high, it is advised to abandon this type of long-term treatment. PMID- 17870556 TI - [Which information should be given to the patient concerning the cardiovascular and renal risk of the NSAIDs?]. AB - OBJECTIVE: Patient information is a topical subject. The aim of this review is to present the rare studies concerning the degree of patient information on the cardiovascular and renal risks of the non-steroidal anti-inflammatory drugs and to suggest some recommendations on this subject. METHODOLOGY: After analysis of the literature (Medline search - January 2006), a series of recommendations has been drawn up following discussion among experts from different specialties (clinical epidemiology, rheumatology, cardiology, nephrology, gastroenterology). RECOMMENDATIONS: It appears necessary to warn all patients of the potential risk of hyperkalemia, renal insufficiency and/or hydrosodium retention (decompensation of an arterial hypertension or a cardiac insufficiency), especially subjects who present risk factors such as age over 75 years, a dehydration, a pre-existing renal disorder, etc. Concerning the risk of arterial thrombotic incident (coronary or cerebral), it is important to indicate that this risk is rare and seems to be observed particularly during prolonged treatments and at high dose. PMID- 17870557 TI - Determination of 240Pu/239Pu atom ratio in coastal surface seawaters from the western North Pacific Ocean and Japan Sea. AB - Surface seawater samples were collected from a site in the vicinity of the nuclear fuel reprocessing facility at Rokkasho, Japan and sites along the Japan Sea coast. (239+240)Pu activities and (240)Pu/(239)Pu atom ratios were determined by alpha-spectrometry and isotope-dilution sector-field ICP-MS. The (240)Pu/(239)Pu atom ratio with the mean value of 0.227 +/- 0.006 was significantly higher than the mean global fallout ratio of 0.18. The contribution of the Pacific Proving Grounds close-in fallout was estimated to be 33% of the (239+240)Pu. PMID- 17870587 TI - Cloning of a cDNA encoding a cystatin from grain amaranth (Amaranthus hypochondriacus) showing a tissue-specific expression that is modified by germination and abiotic stress. AB - A cDNA, encoding a cysteine protease inhibitor (AhCPI), was isolated from an immature seed cDNA library of grain amaranth (Amaranthus hypochondriacus L.) and characterized. It encoded a polypeptide of 247 amino acids (aa), including a putative N-terminal signal peptide. Other relevant regions found in its sequence included the G and PW conserved aa motifs, the consensus LARFAV sequence for phytocystatins and the reactive site QVVAG. The predicted aa sequence for AhCPI showed a significant homology to other plant cystatins. Gene expression analyses indicated that AhCPI was constitutively expressed in mature seeds, and gradually decreased during germination. In vegetative tissues, AhCPI was expressed in the radicle and hypocotyls of seedlings and in the stems and roots of young plantlets. Its expression in roots and stems increased substantially in response to water deficit, salinity-, cold- and heat-stress, whereas heat-stress induced a rapid and transient accumulation of AhCPI transcripts in leaves. The results obtained were suggestive of multiple roles for AhCPI in grain amaranth, acting as a regulator of seed germination and as a protective agent against diverse types of abiotic stress, which induced this gene in a tissue- and stress-specific manner. The work herewith described reports a novel, and apparently, single cystatin protein in which, in agreement with other plant model systems, could have a regulatory role in germination, and further expands previous findings linking the accumulation of protease inhibitors, mostly of the serine proteinase type, with protection against (a)biotic stress in A. hypochondriacus. PMID- 17870569 TI - Glial cell line-derived neurotrophic factor and antioxidants preserve the electrical responsiveness of the spiral ganglion neurons after experimentally induced deafness. AB - Cochlear implant surgery is currently the therapy of choice for profoundly deaf patients. However, the functionality of cochlear implants depends on the integrity of the auditory spiral ganglion neurons. This study assesses the combined efficacy of two classes of agents found effective in preventing degeneration of the auditory nerve following deafness, neurotrophic factors, and antioxidants. Guinea pigs were deafened and treated for 4 weeks with either local administration of GDNF or a combination of GDNF and systemic injections of the antioxidants ascorbic acid and Trolox. The density of surviving spiral ganglion cells was significantly enhanced and the thresholds for eliciting an electrically evoked brain stem response were significantly reduced in GDNF treated animals compared to deafened-untreated. The addition of antioxidants significantly enhanced the evoked responsiveness over that observed with GDNF alone. The results suggest multiple sites of intervention in the rescue of these cells from deafferentation-induced cell death. PMID- 17870588 TI - Inhibition of spinach chloroplast F0F1 by an Fe2+/ascorbate/H2O2 system. AB - Plant chloroplasts are particularly threatened by free radical attack. We incubated purified soluble spinach chloroplast F(0)F(1) (CF(0)F(1), EC 3.6.3.34) with an Fe(2+)/H(2)O(2)/ascorbate system, and about 60% inactivation of the ATPase activity was reached after 60 min. Inactivation was not prevented by omission of H(2)O(2), by addition of catalase or superoxide dismutase, nor by the scavengers mannitol, DMSO, or BHT. No evidence for enzyme fragmentation or oligomerization was detected by SDS-PAGE. The chloroplast ATP synthase is resistant to attack by the reactive oxygen species commonly found at the chloroplast level. DTT in the medium completely prevented the inhibition, and its addition after the inhibition partially recovered the activity of the enzyme. CF(0)F(1) thiol residues were lost upon oxidation. The rate of thiol modification was faster than the rate of enzyme inactivation, suggesting that the thiol residues accounting for the inhibition may be hindered. Enzyme previously oxidized by iodobenzoate was not further inhibited by the oxidative system. The production of ascorbyl radical was identified by EPR and is possibly related to CF(0)F(1) inactivation. It is thus suggested that the ascorbyl radical, which accumulates under plant stress, might regulate CF(0)F(1). PMID- 17870589 TI - Differential expression of 10 sweetpotato peroxidases in response to sulfur dioxide, ozone, and ultraviolet radiation. AB - Secretory class III plant peroxidase (POD, EC 1.11.1.7) is believed to function in diverse physiological processes, including responses to various environmental stresses. To understand the function of each POD in terms of air pollutants and UV radiation, changes in POD activity and expression of 10 POD genes isolated from cell cultures of sweetpotato (Ipomoea batatas) were investigated in the leaves of sweetpotato after treatment with sulfur dioxide (SO(2) 500ppb, 8h/day for 5 days), ozone (O(3) 200ppb, 8h/day for 6 days), and ultraviolet radiation (UV-B 0.6mWm(-2) for 24h, UV-C 0.16mWm(-2) for 24h). All treatments significantly reduced the PSII photosynthetic efficiency (F(v)/F(m)). POD-specific activities (units/mg protein) were increased in leaves treated with SO(2) and O(3) by 5.2- and 7.1-fold, respectively, compared to control leaves. UV-B and UV-C also increased POD activities by 3.0- and 2.4-fold, respectively. As determined by RT PCR analysis, 10 POD genes showed differential expression patterns upon treatment with air pollutants and UV radiation. Among the POD genes, swpa1, swpa2, and swpa4 were strongly induced following each of the treatments. Interestingly, basic POD genes (swpb1, swpb2, and swpb3) were highly expressed following SO(2) treatment only, whereas neutral swpn1 was highly induced following O(3) treatment only. These results indicated that some specific POD isoenzymes might be specifically involved in the defense mechanism against oxidative stress induced by air pollutants and UV radiation in sweetpotato plants. PMID- 17870590 TI - Transcriptional profiling of indica rice cultivar IET8585 (Ajaya) infected with bacterial leaf blight pathogen Xanthomonas oryzae pv oryzae. AB - An indica rice cultivar IET8585 (Ajaya) resists diverse races of the Xanthomonas oryzae pv oryzae pathogen attack, and is often cultivated as bacterial leaf blight (blb) resistant check in India. Earlier we reported a recessive blb resistance gene mapped to the long arm of chromosome 5 in IET8585. Recessive gene mediated blb resistance mechanism is not yet clearly understood. Here we analyzed the transcriptional profile of the blb infected resistant cultivar by rice 22K oligo array. Microarray analysis revealed differential expression of numerous genes at both early (6 h) and late (120 h) stages of infection in the resistant IET8585 cultivar over the susceptible IR24. Some of the differential gene expressions were validated by both RT-PCR and Western blot analysis. Higher expression of ethylene response element binding protein (EREBP) transcription factor along with lower expression of alcohol dehydrogenase gene and reactive oxygen species (ROS) scavenging system may be responsible for hypersensitive cell death in the resistant cultivar upon bacterial infection. Induction of glutathione-mediated detoxification and flavonoid biosynthetic pathways along with up-regulation of defense genes during infection may inhibit pathogen spread in the host tissues. In light of this and previous studies a mechanism of recessive gene-mediated bacterial blight resistance in indica rice is discussed. PMID- 17870591 TI - Sequence, expression and tissue localization of a gene encoding a makorin RING zinc-finger protein in germinating rice (Oryza sativa L. ssp. Japonica) seeds. AB - The makorin (MKRN) RING finger protein gene family encodes proteins (makorins) with a characteristic array of zinc-finger motifs and which are present in a wide array of eukaryotes. In the present study, we analyzed the structure and expression of a putative makorin RING finger protein gene in rice (Oryza sativa L. ssp. Japonica cv. Nipponbare). From the analysis of the genomic (AP003543), mRNA (AK120250) and deduced protein (BAD61603) sequences of the putative MKRN gene of rice, obtained from GenBank, we found that it was indeed a bona fide member of the MKRN gene family. The rice MKRN cDNA encoded a protein with four C3H zinc-finger-motifs, one putative Cys-His zinc-finger motif, and one RING zinc finger motif. The presence of this distinct motif organization and overall amino acid identity clearly indicate that this gene is indeed a true MKRN ortholog. We isolated RNA from embryonic axes of rice seeds at various stages of imbibition and germination and studied the temporal expression profile of MKRN by RT-PCR. This analysis revealed that MKRN transcripts were present at all the time points studied. It was at very low levels in dry seeds, increased slowly during imbibition and germination, and slightly declined in the seedling growth stage. After 6days of germination, an organ-dependent expression pattern of MKRN was observed: highest in roots and moderate in leaves. Similarly to MKRN transcripts, transcripts of cytoskeletal actin and tubulin were also detected in dry embryos, steadily increased during imbibition and germination and leveled off after 24h of germination. We studied the spatial expression profile of MKRN in rice tissues, by using a relatively fast, simple and effective non-radioactive mRNA in situ hybridization (NRISH) technique, which provided the first spatial experimental data that hints at the function of a plant makorin. This analysis revealed that MKRN transcripts were expressed in young plumules, lateral root primordia, leaf primordia, leaves and root tissues at many different stages of germination. The presence of MKRN transcripts in dry seeds, its early induction during germination and its continued spatiotemporal expression during early vegetative growth suggest that MKRN has an important role in germination, leaf and lateral root morphogenesis and overall development in rice. PMID- 17870592 TI - Purification and characterization of native and recombinant SaPIN2a, a plant sieve element-localized proteinase inhibitor. AB - SaPIN2a encodes a proteinase inhibitor in nightshade (Solanum americanum), which is specifically localized to the enucleate sieve elements. It has been proposed to play an important role in phloem development by regulating proteolysis in sieve elements. In this study, we purified and characterized native SaPIN2a from nightshade stems and recombinant SaPIN2a expressed in Escherichia coli. Purified native SaPIN2a was found as a charge isomer family of homodimers, and was weakly glycosylated. Native SaPIN2a significantly inhibited serine proteinases such as trypsin, chymotrypsin, and subtilisin, with the most potent inhibitory activity on subtilisin. It did not inhibit cysteine proteinase papain and aspartic proteinase cathepsin D. Recombinant SaPIN2a had a strong inhibitory effect on chymotrypsin, but its inhibitory activities toward trypsin and especially toward subtilisin were greatly reduced. In addition, native SaPIN2a can effectively inhibit midgut trypsin-like activities from Trichoplusia ni and Spodoptera litura larvae, suggesting a potential for the production of insect-resistant transgenic plants. PMID- 17870608 TI - Analysis of the cleft-lip nose in submental-vertical view, Part I--reliability of a new measurement instrument. AB - BACKGROUND: Objective evaluation of nasal form and symmetry in cleft patients is difficult. The aim of this study was to establish a computer analysis of nasal form and symmetry (intranasal symmetry and symmetrical position of the nose), in order to evaluate primary and secondary cleft rhinoplasty outcomes. MATERIAL AND METHODS: Indirect anthropometric measurements were performed on digital photographs processed by Photoshop 7.0 (Adobe Systems Inc., San Jose, California) with the help of Scion Image software (National Institutes of Health, Maryland, USA). For assessing intranasal symmetry, the ratio of nasal tip projection to total nasal width, the ratio of nostril widths, the ratio of nostril heights, the ratio of mid-alar widths and nostril symmetry were determined. Bifidity of the nose, columellar deviation and angulations of the nostrils were also measured. For assessing the symmetrical position of the nose, the ratio of the distances of alar points to the endocanthial lines and nasal base inclination were determined. The reliability of this analysis was tested by using submento-vertical photographs of bilateral cleft noses, of which the lips were primarily operated on by different techniques and different surgeons in Zurich and Bruges. RESULTS: There were highly significant intraobserver (ICC=0.994) and interobserver reliabilities (ICC=0.893). CONCLUSION: This nasal analysis is appropriate for comparing results of different surgical techniques. PMID- 17870609 TI - Nasalance in patients with maxillary defects - Reconstruction versus obturation. AB - BACKGROUND: An important question remains on how to obtain good quality of speech for patients needing maxillectomy. Oral and nasal spaces must be separated either by surgical means or by using an obturator-prosthesis. An objective measure of oronasal closure is nasalance. Different rehabilitative strategies should be compared. METHODS: Between 1990 and 2000, 88 patients underwent maxillectomy of which 28 (32%) were available for examination. Ten patients had obturators (group l) and in 18 patients the maxilla was biologically reconstructed with different techniques (group 2). Sound pressure of nasal and oral airways were assessed seperately using a computerized sampling system (NasalView) and standardized German texts. Nasalance was calculated and compared with an uncompromised sample of patients. RESULTS: There were no significant differences between group 1 and group 2 concerning nasalance. Furthermore, the achieved values of nasalance were similar to healthy individuals. CONCLUSION: Nasalance after maxillectomy can be normal after sufficient rehabilitation. PMID- 17870610 TI - Update of the European standards for inactive surgical implants in the area of heart valve prostheses. AB - OBJECTIVE: The approval of a heart valve for the European market takes place in accordance with European and international standards. A new version of the EN Standards was published in June 2006, which responded to different technical innovations in the area of heart valve technology. This work outlines the differences between the new EN ISO 5840 (2005) and the old EN 12006-1 (1999). METHODS: We compared the 'new' EN ISO 5840 (2005) and the 'old' EN 12006-1 (1999). RESULTS: The following aspects have been updated in the new EN ISO 5840: Size designation of biological and mechanical heart valve prostheses in accordance with the patient annulus. Differentiation of the annular implantation position (intra-annular, intra-supra-annular, supra-annular). Table for the description of the components of a heart valve prosthesis. Use of compliance chambers for the hydrodynamic testing of prostheses without scaffold. Determination of the minimum requirement for heart valve prostheses in hydrodynamic tests and specification of reference values with regard to prosthesis-related complications in clinical studies. Definition of the requirements for clinical long-term studies (patient number, length). Introduction of an obligatory post-observation timeframe of 5 years for mechanical heart valves and of 10 years for biological heart valves. CONCLUSIONS: The update in the new EN ISO 5840 gives consideration to the technologic evolution of heart valve development. Several changes in the new standard will improve safety for the patient and ensure high quality in the field of heart valve technology. PMID- 17870611 TI - Pharmacokinetic characterization of a pig model of ciclosporin A nephrotoxicity following intravenous administration. AB - BACKGROUND: Recently, we investigated pharmacokinetics and acute nephrotoxicity of oral ciclosporin A (CsA) in pigs. We found that pigs require higher oral CsA doses to obtain comparable area under the concentration versus time curve (AUC) levels to renal transplant patients. The purpose of this study was to examine pharmacokinetics and possible acute renal effects of intravenous CsA in order to further characterize the pig as a model of CsA nephrotoxicity. METHODS: Twenty eight pigs were randomized into four groups: control and three groups subjected to a single CsA infusion at 3, 6, or 9 mg kg(-1). Blood samples for determination of whole blood CsA concentrations were collected over 7 h under general anaesthesia. At 0, 2, and 5 h, we measured blood pressure, serum creatinine, and haemoglobin, as well as renal blood flow (RBF), relative glomerular filtration rate (rGFR), and kidney volume using magnetic resonance imaging. RESULTS: CsA distribution exhibited two-compartmental behaviour. Compared to renal transplant patients, pigs had approximately the same total clearance of CsA (mean 0.31 0.34lh(-1)kg(-1)), which yields comparable AUC after equivalent dosage in both species. However, the volume of distribution at steady state (mean 1.9-3.0lkg( 1)) was lower in pigs. RBF remained stable in all groups, whereas rGFR decreased in all groups reaching statistical significance in the controls. CONCLUSIONS: Pigs require approximately the same intravenous CsA doses to obtain comparable total AUC to renal transplant patients. Single CsA infusion up to 9 mg kg(-1) for 1h has no deteriorating effect on renal haemodynamics and function. PMID- 17870612 TI - Quantitative comparison of IMAC and TiO2 surfaces used in the study of regulated, dynamic protein phosphorylation. AB - Protein phosphorylation regulates many aspects of cellular function, including cell proliferation, migration, and signal transduction. An efficient strategy to isolate phosphopeptides from a pool of unphosphorylated peptides is essential to global characterization using mass spectrometry. We describe an approach employing isotope tagging reagents for relative and absolute quantification (iTRAQ) labeling to compare quantitatively commercial and prototypal immobilized metal affinity chelate (IMAC) and metal oxide resins. Results indicate a prototype iron chelate resin coupled to magnetic beads outperforms either the Ga(3+)-coupled analog, Fe(3+), or Ga(3+)-loaded, iminodiacetic acid (IDA)-coated magnetic particles, Ga(3+)-loaded Captivate beads, Fe(3+)-loaded Poros 20MC, or zirconium-coated ProteoExtract magnetic beads. For example, compared with Poros 20MC, the magnetic metal chelate (MMC) studied here improved phosphopeptide recovery by 20% and exhibited 60% less contamination from unphosphorylated peptides. With respect to efficiency and contamination, MMC performed as well as prototypal magnetic metal oxide-coated (TiO(2)) beads (MMO) or TiO(2) chromatographic spheres, even if the latter were used with 2,5-dihydroxybenzoic acid (DHB) procedures. Thus far, the sensitivity of the new prototypes reaches 50 fmol, which is comparable to TiO(2) spheres. In an exploration of natural proteomes, tryptic (phospho)peptides captured from stable isotopic labeling with amino acids in cell culture (SILAC)-labeled immunocomplexes following EGF treatment of 5 x 10(7) HeLa cells were sufficient to quantify stimulated response of over 60 proteins and identify 20 specific phosphorylation sites. PMID- 17870613 TI - A method to determine the ionization efficiency change of peptides caused by phosphorylation. AB - Quantitative assessment of post-translational modifications in proteins by mass spectrometry often requires the consideration of the alteration in ionization efficiency of peptides induced by the modification. Herein, we introduced a method to measure the relative ionization efficiencies of peptides using specifically designed unlabeled peptides. In our design, the peptide under study, in either the unmodified or modified form, is linked with an internal standard peptide via an enzyme cleavage site; thus, after enzymatic digestion, we could obtain readily a 1:1 ratio between the peptide under investigation and the internal standard peptide. The relative ionization efficiencies of the modified and unmodified peptides can then be calculated from the modification-induced change in the ratio of relative abundances of the ion of the peptide of interest over that of the internal standard peptide. We demonstrated the usefulness of the method by assessing the change in ionization efficiencies of four peptides introduced by phosphorylation. PMID- 17870614 TI - Influence of attentional demands on the processing of emotional facial expressions in the amygdala. AB - Recent studies have cast doubts on the appealing idea that the processing of threat-related stimuli in the amygdala is unconstrained by the availability of attentional resources. However, these studies exclusively used face stimuli presented at fixation and it is unclear whether their conclusion can apply to peripheral face stimuli. Thus, we designed an experiment in which we manipulated the perceptual attentional load of the task used to divert attention from peripheral face stimuli: participants were presented simultaneously with four peripheral pictures (two faces, either both neutral or both fearful, and two houses) that were slightly tilted, and had to match two of these pictures (defined by their position on the screen) either for orientation of the tilt or for identity. The identity task was confirmed to involve greater attentional load than the orientation task by differences in accuracy, reaction times, subsequent face recognition performance, and patterns of activation in several cortical regions. In the orientation task, ignored fearful faces led to stronger activation in the right amygdala than ignored neutral faces. However, this differential response was abolished when participants performed the difficult identity-matching task. Thus, emotional processing of peripheral faces in the amygdala also appears to depend on the available perceptual attentional resources. PMID- 17870616 TI - The phylogeny of cobras inferred from mitochondrial DNA sequences: evolution of venom spitting and the phylogeography of the African spitting cobras (Serpentes: Elapidae: Naja nigricollis complex). AB - We use phylogenetic analysis of 1333 bp of mitochondrial DNA sequence to investigate the phylogeny and historical biogeography of the cobra-like elapid snakes, with special reference to the evolution of spitting and the phylogeography of the African spitting cobras, a radiation widespread in open vegetational formations throughout sub-Saharan Africa. Our results suggest that spitting adaptations appear to have evolved three times in cobras, but alternative scenarios cannot be rejected. The Asiatic Naja are monophyletic and originate from a single colonization of Asia from Africa. The radiation of the African spitting Naja appears to date back to the early Miocene and many speciation events in the group predate the Pliocene expansion of grasslands and the radiation of large grazing mammals in Africa. The cladogenic events in this complex appear to have been triggered by both ecological changes and tectonic events associated with the formation and expansion of the African Rift Valley. Taxonomically, our data confirm the inclusion of Boulengerina and Paranaja within Naja, and reveal a clade of African rainforest cobras including N. melanoleuca, Paranaja multifasciata and Boulengerina that constitutes the sister clade of the African open-formation non-spitting cobras. Naja nigricollis is polyphyletic, and we therefore recognize N. nigricincta as a separate species, more closely related to N. ashei and N. mossambica than to N. nigricollis. PMID- 17870617 TI - The symptoms of varicose veins: difficult to determine and difficult to study. AB - OBJECTIVES: To investigate the activities which may exacerbate symptoms in patients with varicose veins. METHODS: Questionnaires sent to patients before clinics and at least six months later. RESULTS: Both questionnaires were returned by 149 of 203 patients (74%) but only 124 contained adequate data for comparison- 55 from patients who had surgical treatment and 69 who had no surgery. At initial presentation, worsening of discomfort attributed to varicose veins was common during (58%) or after (48%) standing and in hot weather (44%), but less when sitting with the feet down (31%), and after (31%) or when walking (19%). Surgery significantly reduced the total number of symptoms reported by patients at follow up (p<0.02). However, none of the symptoms reported during specific activities was significantly lessened by surgery compared with no treatment--possibly because the attrition of patients during the study resulted in small numbers for analysis. CONCLUSIONS: Symptoms are a common indication for treating varicose veins and it is therefore important to be sure that they are due to the veins, rather than other causes. This report highlights traditional and logical questions which may help to identify symptoms caused by varicose veins but illustrates the difficulty of validating them. PMID- 17870615 TI - Multiparametric magnetic resonance imaging analysis of the corticospinal tract in multiple sclerosis. AB - BACKGROUND/PURPOSE: Muscle weakness is an important feature of multiple sclerosis and is responsible for much of the disability associated with that condition. Here, we describe the quantitative magnetic resonance imaging (MRI) attributes of the major intracerebral motor pathway--the corticospinal tract--in multiple sclerosis. To do so, we develop an intuitive method for creating and displaying spatially normalized tract-specific imaging data. METHODS: In 75 individuals with multiple sclerosis and 29 healthy controls, the corticospinal tracts were reconstructed from diffusion tensor imaging at 3 T. Multiple MRI indices--T2 relaxation time; fractional anisotropy; mean, longitudinal, and transverse diffusivity; and magnetization transfer ratio--were examined within the reconstructed tracts. Spatially normalized tract profiles were created to compare, across subjects, the variation in MRI index as a function of tract position. RESULTS: Each index's tract profile had a characteristic shape. Individual subjects had markedly abnormal tract profiles, particularly at lesion sites. On average, tract profiles were different between patients and controls, particularly in the subcortical white matter and corona radiata, for all indices examined except for fractional anisotropy. Magnetization transfer ratio was further decreased in subjects with secondary progressive disease. Tract asymmetry was increased in multiple sclerosis compared to controls. CONCLUSION: Multiparametric MRI allows rapid detection, localization, and characterization of tract-specific abnormalities in multiple sclerosis. Tract profiles bridge the gap between whole-brain imaging of neurological disease and the interrogation of individual, functionally relevant subsystems. PMID- 17870618 TI - Antigen-specific immunity following hematopoietic stem cell transplantation. AB - Most studies evaluating immune reconstitution following hematopoietic stem cell transplantation (HSCT) have focused on immunophenotypic analysis and the capacity of the immune system to respond to mitogenic stimulation. However, protection against infectious pathogens and potentially anti-tumor responses correlate with the presence of antigen-specific immunity, not the immunophenotypic presence of T lymphocytes. Antigen-specific T lymphocytes present after HSCT can be derived from donor antigen-specific T lymphocytes present in the transplantation inoculum if it is not T cell depleted. Furthermore, the naive T lymphocytes contained in the HSCT inoculum have the potential to develop into antigen-specific T lymphocytes. If the transplantation inoculum is T cell depleted, then all antigen specific T lymphocytes will have to be derived from the newly engrafted hematopoietic stem cells following their differentiation through the recipient thymus. Thus, defects in thymopoiesis will result in delays or the absence of naive T lymphocytes and ultimately defects in antigen-specific immunity. PMID- 17870619 TI - Regarding "A positive or a negative confounding variable? A simple teaching aid for clinicians and students". PMID- 17870620 TI - Molecular phylogenetics of ascomycotal adhesins--a novel family of putative cell surface adhesive proteins in fission yeasts. AB - In this work, we identify a family of putative adhesins in the fission yeasts Schizosaccharomyces pombe and Schizosaccharomyces japonicus. The members of this family share a conserved tandem repeat related to those found in the Candida albicans Als family of adhesins. Unlike previously characterised adhesins that possess conserved ligand-binding domains at the N-terminus, this group of proteins carry ligand-binding domains at their C-termini. We demonstrate that one such domain--the uncharacterised GLEYA domain, is related to the lectin-like ligand-binding domain found in the Saccharomyces cerevisiae Flo proteins. Unlike the Flo and Als proteins, the fission yeast adhesins do not contain detectable glycosyl phosphatidyl inositol (GPI) membrane anchor signals to mediate their attachment to the cell wall, which may suggest a novel cell wall attachment mechanism. Further sequence analysis identified several putative adhesins in the sub-phylum of Pezizomycotina, where only a few adhesins have been described to date. PMID- 17870622 TI - Cytoarchitecture of the cerebral cortex--more than localization. AB - The present paper reviews that macroanatomical landmarks are problematic for a reliable and sufficiently precise localization of clusters of activation obtained by functional imaging because sulcal and gyral patterns are extremely variable and macroanatomical landmarks do not match (in nearly all cases) architectonically defined borders. It argues that cytoarchitectonic probabilistic maps currently offer the most precise tool for the localization of brain functions as obtained from functional imaging studies. Finally, it provides some examples that cytoarchitecture is more than localization with respect to a particular brain region because it reflects the inner organization of cortical areas and, furthermore, functional principles of the brain. PMID- 17870621 TI - In praise of tedious anatomy. AB - Functional neuroimaging is fundamentally a tool for mapping function to structure, and its success consequently requires neuroanatomical precision and accuracy. Here we review the various means by which functional activation can be localised to neuroanatomy and suggest that the gold standard should be localisation to the individual's or group's own anatomy through the use of neuroanatomical knowledge and atlases of neuroanatomy. While automated means of localisation may be useful, they cannot provide the necessary accuracy, given variability between individuals. We also suggest that the field of functional neuroimaging needs to converge on a common set of methods for reporting functional localisation including a common "standard" space and criteria for what constitutes sufficient evidence to report activation in terms of Brodmann's areas. PMID- 17870623 TI - The spectrum of herpes simplex encephalitis in children. AB - Clinical and basic science research carried out in recent years into herpes simplex encephalitis (HSE) have shown that the concept of a "classical" picture of HSE in children is now outdated and that our current knowledge of the disease is probably only the tip of an iceberg. Indeed, increasing evidence supports the existence of a wider range of pathophysiological mechanisms, clinical presentations and disease progressions in paediatric HSE. This paper reviews the clinical, biological and radiological data available and redefines the spectrum of HSE in children. Full understanding of the condition should improve the management of suspected cases and decrease the morbidity and the mortality associated with this disease. PMID- 17870624 TI - A new episode of low back pain: who relies on bed rest? AB - Bed rest has been shown to be an ineffective treatment for non-specific low back pain (LBP). Despite this, during a new episode of pain some patients still rely on bed rest. Which patients choose bed rest is however unknown. The objectives of the present study were, firstly, to assess characteristics of patients choosing bed rest in (sub)acute pain and secondly to study whether prolonged bed rest in the (sub)acute phase of pain will result in long term disability. A prospective longitudinal cohort study included 282 patients with non-specific LBP for less than 7 weeks. Main outcome measures were duration of bed rest (in three categories) and disability. Results showed that 33% of patients with (sub)acute LBP had bed rest, but only 8% stayed in bed for more than four days. An ordinal regression analysis revealed that behavioural factors (catastrophizing (OR=1.05 per bed rest category p<0.01)) and fear of injury (OR=1.05 per category p<0.01) rather than specific pain related factors (pain history (OR=0.61 per category p=0.16) and pain intensity (OR=1.00 per category p=0.63)) were associated with bed rest. Patients with prolonged bed rest in an early phase of pain were still more disabled after one year (p<0.01). Based on these results we conclude that prolonged bed rest in the early phase of pain is associated with a higher long term disability level. In preventing low back disability, GP screening for catastrophizing and fear of injury in LBP patients who had prolonged bed rest merits consideration. PMID- 17870625 TI - Comparison of epidural analgesia and intercostal nerve cryoanalgesia for post thoracotomy pain control. AB - Epidural analgesia is regarded as the gold method for controlling post thoracotomy pain. Intercostal nerve cryoanalgesia can also produce satisfactory analgesic effects, but is suspected to increase the incidence of chronic pain. However, randomized controlled trials comparing these two methods for post thoracotomy acute pain analgesic effects and chronic pain incidents have not been conducted previously. We studied 107 adult patients, allocated randomly to thoracic epidural bupivacaine and morphine or intercostal nerve cryoanalgesia. Acute pain scores and opioid-related side effects were evaluated for three postoperative days. Chronic pain information, including the incidence, severity, and allodynia-like pain, was acquired on the first, third, sixth and twelfth months postoperatively. There was no significant difference on numeral rating scales (NRS) at rest or on motion between the two groups during the three postoperative days. The patient satisfaction results were also similar between the groups. The side effects, especially mild pruritus, were reported more often in the epidural group. Both groups showed high incidence of chronic pain (42.1 72.1%), and no significance between the groups. The incidence of allodynia-like pain reported in cryo group was higher than that in Epidural group on any postoperative month, with significance on the sixth and the twelfth months postoperatively (P<0.05). More patients rated their chronic pain intensity on moderate and severe in cryo group and interfered with daily life (P<0.05). Both thoracic epidural analgesia and intercostal nerve cryoanalgesia showed satisfactory analgesia for post-thoracotomy acute pain. The incidence of post thoracotomy chronic pain is high. Cryoanalgesia may be a factor that increases the incidence of neuropathic pain. PMID- 17870626 TI - Expression and distribution of fugu TIMP-2s (fgTIMP-2a and fgTIMP-2b) mRNAs in tissues and embryos. AB - In teleosts, two distinct types of TIMP-2s occur, TIMP-2a and TIMP-2b, but little is known about their locations and quantitative expressions. Here, we examined pufferfish (Takifugu rubripes) TIMP-2a (fgTIMP-2a) and TIMP-2b (fgTIMP-2b) quantities and locations in fugu adult tissues and embryos. To compare the quantitative expression of fgTIMP-2s, we performed a quantitative real-time PCR (qPCR). FgTIMP-2a mRNA was constitutively expressed and significant differences in expression were not observed among adult tissues. Whereas, fgTIMP-2b mRNA was significantly differently expressed in ordinary muscle and gill compared to the expression level in whole blood (P<0.05). Although significant difference was not observed between brain and other tissues, both fgTIMP-2s mRNAs were abundant in the brain. In addition, we examined embryos during development using qPCR. Both fgTIMP-2s mRNAs gradually increased during embryonic development from 48 hpf. However, fgTIMP-2b mRNA was obviously abundant compared to fgTIMP-2a mRNA in embryos. We also examined the specific mRNA distribution in embryos. The fgTIMP 2s mRNAs showed the same distribution during development. Both fgTIMP-2s are expressed in adult fugu tissues and embryos but their expression levels clearly differ, suggesting that there is a predominance of fgTIMP-2b over fgTIMP-2a in vivo. PMID- 17870627 TI - Association between obesity and insulin resistance with UCP2-UCP3 gene variants in Spanish children and adolescents. AB - A number of studies have yielded controversial results on the association between polymorphisms in UCP2 and UCP3 genes with obesity and its comorbidities. The discrepancy among studies might be partially explained by the lack of consideration of the effect of adjacent loci in the same haplotype and the exclusion of key lifestyle factors in the statistical analysis. In this study, we have assessed the association between three genetic variants of the UCP2-UCP3 gene cluster, the -866G/A (rs659366) and the 45bp insertion (in position 173247 of the AC019121) of the UCP2 gene, the -55C/T (rs1800849) polymorphism of the UCP3 gene and their estimated haplotypes with childhood obesity and insulin resistance. This research was designed as a case-control study and information about several environmental parameters such as leisure time physical activity and time spent watching television were included. The study sample consisted in 193 obese children and adolescents (cases) and 170 controls aged 6-18. We found that the individual polymorphisms were not associated with obesity, but the (-866G; rs659366)-(Del; 45bp)-(-55T; rs1800849) haplotype was significantly associated with obesity and its presence in the control group increased about nine times the insulin resistance risk. Thus, the (-866A; rs659366)-(Ins; 45bp)-(-55C; rs1800849) haplotype may protect against insulin resistance in the obese population group. PMID- 17870628 TI - [Report of adverse events related to treatments to Institute de Veille sanitaire]. AB - The code de sante publique imposes to all health professionals an obligation to declare serious and undesirable events following cares applied during treatment investigations or prevention actions. An experimentation has been installed under the responsibility of the Institut de Veille sanitaire further to the 9 August 2004 bill. It aims to define how to declare undesirable adverse events to test its feasibility, its efficiency and to identify the necessary conditions to widespread its modalities. The field of these experimentations concerns all health professionals, working in public hospital or in private practice. The definition of undesirable adverse events should be clarified. Different ways to declare these events will be discussed with SFRO (Societe francaise de radiotherapie oncologique) to improve the current management of incidents and adverse events. PMID- 17870629 TI - [Reconstruction of the trapeziometacarpal joint and the first metacarpal bone by reversed free osteocutaneous dorsalis pedis flap]. AB - A case of reconstruction after first metacarpal resection by reversed free vascularized osteocutaneous pedis flap is presented. This procedure avoids bone resorption and preserves the trapezio metacarpal joint contrary to conventional bone graft. A double rotation is applied to the flap: the head of the metatarsal becomes proximal and the palmar side becomes dorsal. The metacarpo-phalangeal joint undergo arthrodesis. With a follow up of three years, there is no pain, the Kapandji score is 8/10 (very good range of motion), there is no osteoarthritis. PMID- 17870630 TI - [Twin-to-twin delivery interval: is a time limit justified?]. AB - OBJECTIVES: To assess the effect of the twin-to-twin delivery interval on the umbilical cord blood gas status and the neonatal outcome of the second twin following vaginal delivery. PATIENTS AND METHODS: Retrospective study of twin deliveries at or beyond 34 weeks of gestation over a period of five years. The correlation between the twin-to-twin delivery interval, and the umbilical arterial blood gas parameters of the second twin, including pH, PO(2), PCO(2), HCO(3-) and base excess, was studied. A second analysis was performed after exclusion of non-vertex presentation, need for general anesthesia, growth restriction and weight difference between the twin>30%. RESULTS: Two hundred and thirty-nine patients were studied. The mean twin-to-twin delivery interval was 11.3+/-6.4 minutes (between 6 and 14 minutes in 56.1% of cases). The second twin had more Apgar score<7 at 1 minute (P<0.02) and more arterial ombilical pH<7.20 (P<0.01) than the first twin. Over 15 minutes, the mean arterial pH was lower (P<0.01) and the number of arterial pH<7.20 increased (P<0.03). In contrast, the mean Apgar score and the rate of neonatal transfer did not differ significantly. There were significant negative correlations between arterial pH, base excess and bicarbonates and the twin-to-twin delivery interval (P<0.05). Similar results were found in the homogenised population. The reduction in the second twin arterial pH was expressed as pH=7.282-0.003 x time. DISCUSSION AND CONCLUSION: Umbilical cord arterial blood gas parameters deteriorate with increasing twin-to twin delivery interval. Our results suggest that this interval should be less than 15 minutes, but obstetrician should adapt to every clinic situation. PMID- 17870631 TI - Revisiting rabies in Japan: is there cause for alarm? AB - Since 1957 Japan has successfully eradicated human and animal rabies through registration, confinement and compulsory vaccination of family dogs, and elimination of stray dogs. However, in November 2006, two cases of human rabies infections were reported in the country. These patients were bitten by dogs during travel in the Philippines, and did not receive pre- and post-exposure prophylaxes. With the mounting numbers of Japanese travelers every year, the risk of infection increases especially to those who visit regions where the disease is endemic. In this paper, we shall discuss the two recent human deaths from rabies, review the current situation and control measures in Japan and surrounding countries where the disease is prevalent, summarize precautionary measures for travelers, and suggest public health strategies to prevent the re-introduction of rabies in the country. PMID- 17870632 TI - Food-poisoning and commercial air travel. AB - With the introduction of budget airlines and greater competitiveness amongst all airlines, air travel has now become an extremely popular form of travel, presenting its own unique set of risks from food poisoning. Foodborne illness associated with air travel is quite uncommon in the modern era. However, when it occurs, it may have serious implications for passengers and when crew are affected, has the potential to threaten safety. Quality, safe, in-flight catering relies on high standards of food preparation and storage; this applies at the airport kitchens (or at subcontractors' facilities), on the aircraft and in the transportation vehicles which carry the food from the ground source to the aircraft. This is especially challenging in certain countries. Several foodborne outbreaks have been recorded by the airline industry as a result of a number of different failures of these systems. These have provided an opportunity to learn from past mistakes and current practice has, therefore, reached such a standard so as to minimise risk of failures of this kind. This review examines: (i) the origin of food safety in modern commercial aviation; (ii) outbreaks which have occurred previously relating to aviation travel; (iii) the microbiological quality of food and water on board commercial aircraft; and (iv) how Hazard Analysis Critical Control Points may be employed to maintain food safety in aviation travel. PMID- 17870633 TI - Understanding sexual relationships between tourists and locals in Cuzco/Peru. AB - BACKGROUND: Casual sexual encounters between tourists and locals have been increasingly discussed. The city of Cuzco/Peru is well known for an increased availability of such sexual opportunities. The objective of this study was to explore tourists' and locals' knowledge, attitudes, and reasoning for engaging in casual sexual relationships. METHOD: In this qualitative study, 10 locals and 13 tourists were in-depth interviewed (15 women, 8 men, aged 19-50+). Participant and non-participant observations, and informal discussions provided supporting evidence. RESULTS: For tourists, the relationships with locals ranged from one night-stands as part of the travel experience and having fun, to commitment for the term of a longer stay, to marriage. From the locals' point of view, these encounters ranged from sexual adventures to increase self-esteem and high standing in their circle of friends, to serious long-term commitments. In both cases, the difference in the physical appearance played a main part in the perceived attraction that had triggered the encounter. Lack of consistent condom use remains a concern along with the locals' profound lack of knowledge of STIs. CONCLUSIONS: Travel health advisors should place more emphasis on sexual health in pre-travel consultations. The use of condoms cannot be stressed enough. Local health professionals should aggressively increase safe sex health promotion, specifically targeting people related to the tourism industry. PMID- 17870634 TI - High case-fatality from falciparum malaria in UK travellers returning from The Gambia: a case series. AB - BACKGROUND: Following two deaths from falciparum malaria in UK travellers returning from The Gambia, we investigated the epidemiology of cases during part of the "winter sun" season in 2005/2006. METHOD: We obtained data on laboratory confirmed cases of falciparum malaria (diagnosed 1.11.2005 to 31.1.2006) in travellers returning from The Gambia. Information on prophylaxis and deaths, for all Gambia associated cases from 2000 to 2004, and for cases from all countries between 1.11.2005 and 31.10.2006 (excluding series cases), was used for comparison. We obtained Gambian tourist figures from the World Tourism Organisation. RESULTS: Twenty-six cases of falciparum malaria were identified between 1.11.05 and 31.1.06 (32 during the entire year), of whom three died and seven required intensive care. Twenty cases (80%) were on holiday, and half the year's cases were diagnosed in December. Of the 24/26 where it was determined, half had taken no prophylaxis and half had taken inadequate prophylaxis. The annual risk was 75 per 100,000 charter flight passengers. CONCLUSIONS: Compliance with chemoprophylaxis was poor and the case-fatality rate high (11.5% vs. 3.8% in 2000-2004). A clear message emphasising the importance of chemoprophylaxis, bite avoidance and prompt diagnosis was disseminated to clinicians, public and the travel industry. PMID- 17870635 TI - Plasmodium vivax-associated acute respiratory distress syndrome after extended travel in Afghanistan. AB - A 21-year-old soldier developed anorexia, vomiting, diarrhea and fever 10 days after returning to the United States from an 8-month deployment in Afghanistan. His symptoms persisted over the next 5 days until he presented in respiratory failure with a partial pressure oxygen: concentration of inspired oxygen (PaO(2):FiO(2)) ratio of 63, requiring urgent intubation and ventilator support. Chest roentgenogram revealed diffuse bilateral alveolar opacities consistent with acute respiratory distress syndrome. Although sputum and blood cultures did not reveal a causative agent, Giemsa-stained blood smears were positive for Plasmodium vivax alone, which was later confirmed by small subunit ribosomal RNA polymerase chain reaction amplification. After a tenuous course marked by splenic rupture and prolonged requirement for ventilator support, the patient ultimately recovered. Although generally considered benign, this and other recent reports of vivax malaria-associated lung injury emphasize the need for persistent pursuit of the diagnosis in febrile travelers returning from vivax endemic locations as well as aggressive monitoring for and management of life-threatening complications. PMID- 17870636 TI - Mefloquine versus 3-day oral quinine-clindamycin in uncomplicated imported falciparum malaria. AB - In this open randomized trial comparing 3-day oral quinine-clindamycin versus standard mefloquine regimen for uncomplicated imported falciparum malaria, mefloquine treatment was associated with a higher risk of discontinuation of the treatment (RR=1.8, 95% CI [1.1-2.8]) related to mainly mild gastrointestinal adverse drug events. The poor tolerability of mefloquine sets a question mark against its use in outpatients. PMID- 17870637 TI - Value of rapid testing for influenza among Hajj pilgrims. AB - BACKGROUND: Muslim pilgrims going on the Hajj are at risk of influenza. The treatment and prevention of influenza with antiviral drugs depends on rapid diagnosis using a near-patient test such as the QuickVue influenza test. The suitability of this test among pilgrims has not been studied in the past and this study assesses the usefulness of the test for diagnosing influenza among those attending the Hajj. METHODS: The sensitivity and specificity of the QuickVue test were measured against reverse transcriptase polymerase chain reaction by undertaking the tests on nasal swab samples from pilgrims. RESULTS: The sensitivity and specificity of the QuickVue test were 22% and 99%, respectively, and its likelihood ratio for a positive and a negative test were 22 and 0.79 in that order. CONCLUSION: The QuickVue influenza test using nasal swabs is poorly sensitive for diagnosing influenza among Hajj pilgrims. Given its high specificity and an even higher likelihood ratio for a positive test it may still be a very useful tool for influenza surveillance at the Hajj. PMID- 17870638 TI - An optimization study using response surface methods on the decolorization of Reactive Blue 19 from aqueous solution by ultrasound. AB - The decolorization of reactive dye C.I. Reactive Blue 19 from aqueous solution was studied by using ultrasound, activated carbon and combined ultrasound/activated carbon. The combined effects of independent variables, such as ultrasound power, temperature, time, activated carbon concentration, dye concentration and initial pH were investigated on the decolorization by using the central composite design. The decolorization of RB 19 was modelled statistically and optimized by means of the Matlab computer software. The decolorization were accomplished at optimum conditions by using ultrasound, activated carbon and combined ultrasound/activated carbon as 36%, 91% and 99.9%, respectively. The application of ultrasonic irradiation was found to be beneficial for decolorization of RB 19 from aqueous solution by adsorption. PMID- 17870639 TI - Playing catch in the park. PMID- 17870640 TI - Academic general pediatric fellowships: curriculum design and educational goals and objectives. AB - Academic generalists are unique and important members of the pediatric landscape.(1) Academic general pediatrics (AGP) is not considered a subspecialty, because it adheres to generalist values and embraces a wide range of clinical activities. Nonetheless, academic generalists engage in important scholarly efforts, contribute extensively to the education of new pediatricians, and must be prepared to survive in academia. Academic general pediatric faculty positions are subject to the same appointment and promotion requirements as those of subspecialist faculty. PMID- 17870641 TI - Strengthening the academic base of general pediatrics fellowship programs: a national program and curriculum development project. AB - OBJECTIVE: To improve academic general pediatrics (AGP) fellowship programs by 1) developing curriculum guidelines and program standards and 2) creating a process for program review and consultation that might later be used for accreditation of AGP fellowship programs. METHODS: This project of the Ambulatory Pediatric Association (APA) created 4 documents: AGP fellowship program requirements, core curriculum, educational goals and objectives, and a standardized form to describe required program characteristics. Site visits were conducted at 7 volunteer AGP fellowship programs, selected for diversity of content, structure, and location. Evaluations were conducted using a uniform checklist of requirements that combined numerical ratings with a written evaluation summary. Feedback from programs on the review process enabled refinement of the documents. RESULTS: The site visits revealed great variety in emphasis among the 7 programs. In general, faculty were dedicated and capable, and programs showed considerable educational strengths. Typical problems were lack of integration of the program within departmental structures, overburdened faculty, and uncertain funding. Many programs demonstrated suboptimal curriculum planning and weak evaluation methods. Most program leaders felt that the project materials helped to improve the quality of their programs, and 5 of 7 programs expressed willingness to be involved in formal accreditation review in the future. CONCLUSIONS: AGP fellowship programs that volunteered for piloting of an accreditation process were diverse and vital, with rich educational offerings despite a lack of optimal curriculum structure, minimal evaluation, limited faculty resources, and tenuous funding. An APA accreditation process appears to be feasible and may enhance AGP fellowship programs. PMID- 17870642 TI - Pediatric residents' and continuity clinic preceptors' perceptions of the effects of restricted work hours on their learning relationship. AB - OBJECTIVE: The effects of the Work Hour Standard (WHS) on continuity of care and quality of education has stimulated much discussion, yet little is known about how it affects the resident-continuity clinic preceptor (CCP) dyad, the only longitudinal learning relationship in pediatric residency. This case study explored residents' and CCPs' perceptions of the effects of restricted work hours on their learning relationship. METHODS: Direct observation of third-year pediatric residents (n = 10) and their CCPs (n = 10) was carried out in continuity clinic (CC) for 5 months; both groups attended clinic before and after the WHS. Semistructured, audiotaped interviews were conducted with residents before and after observation, and with CCPs after resident data were collected. Data from interview transcripts and observational notes were analyzed for major themes. RESULTS: To comply with the WHS, postcall clinic was eliminated and residents were rescheduled to another afternoon CC. The consequence of eliminating postcall clinic, disruption in the resident-CCP relationship, was perceived differently by residents and CCPs. From the residents' perspective, rescheduling CC in response to the WHS benefited their learning because it exposed them to different CCPs with different practice styles. From the CCPs' perspective, rescheduling CC frustrated their efforts to be learner-centered teachers and effective mentors. CONCLUSIONS: Intended changes to limit excessive work hours had unintended effects that were viewed more favorably by residents than by CCPs. Understanding the shared and different perspectives of residents and preceptors regarding WHS-related changes in CC extends the discussion of the effect of restricted work hours. PMID- 17870643 TI - Exam room presentations and teaching in outpatient pediatrics: effects on visit duration and parent, attending physician, and resident perceptions. AB - OBJECTIVE: To examine the effects of exam room presentations and teaching (ERPT) in a busy outpatient pediatric setting on visit duration and on parent, preceptor, and resident perceptions. METHODS: This 8-week, 2-method crossover study compared first-year pediatric resident patient presentations and attending physician teaching and discussion in the exam room (ERPT) with conference area presentation and teaching (CAPT). Outcome measures included visit duration, parent satisfaction, and resident/attending physician perceptions. Differences were analyzed using chi2 (parent surveys), t tests (visit duration), and signed rank tests (Attending Physician and Resident Surveys). RESULTS: Three hundred forty patient encounters were studied (151 ERPT vs 189 CAPT) that involved 15 first-year pediatric residents and 15 attending physicians. Visit durations were equivalent. Parent satisfaction was high in both methods. Attending physicians favored ERPT for adding opportunities to evaluate resident competencies, provide informed feedback, and role model. Attending physicians felt that ERPT decreased resident comfort level when discussing sensitive topics. Residents were less comfortable with ERPT for discussing sensitive topics and felt somewhat embarrassed when they did not know the answer to attending physicians' questions. Residents reported that ERPT presentations permitted attending physicians to demonstrate more physical exam skills and to observe interactions, enabling more informed feedback. CONCLUSIONS: ERPT and CAPT require similar time and result in high parent satisfaction. Although residents are a little less comfortable with ERPT, attending physicians are better able to observe, evaluate, and give feedback on resident skills and to role model and teach physical diagnosis. PMID- 17870644 TI - Male partner pregnancy-promoting behaviors and adolescent partner violence: findings from a qualitative study with adolescent females. AB - OBJECTIVE: To examine the context of pregnancy and sexual health among adolescent females with a history of intimate partner violence (IPV). This paper reports on a subset of females who described abusive male partners' explicit pregnancy promoting behaviors (ie, messages and behaviors that led females to believe their partner was actively trying to impregnate them). METHODS: Semistructured interviews were conducted with 53 sexually active adolescent females, with known history of IPV, about violence, sexual experiences, and related behaviors. Interviews were analyzed using a content analysis approach; 14 interviews in which females reported that partners were actively trying to impregnate them were further analyzed for pregnancy and contraceptive use. RESULTS: Participants (N = 53) were aged 15 to 20 years, with notable minority representation, 21% African American (n = 11) and 38% Latina (n = 20). Over half (n = 31, 58%) had experienced pregnancy. A key finding was that approximately one quarter of participants (26%, n = 14) reported that their abusive male partners were actively trying to get them pregnant. Females' stories revealed that abusive male partners desiring pregnancy manipulated condom use, sabotaged birth control use, and made explicit statements about wanting her to become pregnant. CONCLUSIONS: Pregnancy-promoting behaviors of male abusive partners may be one potential mechanism underlying associations between adolescent IPV and pregnancy. These findings suggest that exploring pregnancy intentions and behaviors of partners of sexually active adolescents may help to identify youth experiencing IPV. The frequency of birth control sabotage and explicit attempts to cause pregnancy in adolescent IPV needs to be examined at the population level. PMID- 17870645 TI - Factors influencing pediatricians' intention to recommend human papillomavirus vaccines. AB - OBJECTIVES: The objectives of this qualitative study were to describe the range of pediatricians' attitudes about human papillomavirus (HPV) vaccines and to explore factors influencing their intention to recommend HPV vaccines, extending the findings of previous quantitative studies. METHODS: A diverse sample of pediatricians participated in semistructured individual interviews to assess attitudes and intentions regarding HPV immunization. Framework analysis was used for qualitative analysis. RESULTS: The mean age of the 31 participants was 47 years, 17 (55%) were female, 9 (29%) were black, and 4 (13%) were Latino. The efficacy, safety, and potential health impact of vaccination were the primary factors driving participants' decisions about recommending HPV vaccines. Perceived benefits of HPV vaccination included prevention of HPV-related disease and the opportunity to educate adolescents. Perceived barriers included anticipated parental beliefs (eg, parental denial that their child would be at risk) and provider beliefs (eg, reluctance to discuss sexuality with preadolescents). Participants reported high intention to recommend HPV vaccines overall, but intention varied according to patient age, patient gender, and HPV vaccine type. The primary reasons underlying this variation included perceptions about the health impact of vaccination and relevance of HPV vaccines to the provider's patients. The main factors driving intention to recommend HPV vaccines included knowledge, personal and professional characteristics, office procedures, vaccine cost and reimbursement, parental factors, and specific attitudes about HPV vaccination. CONCLUSIONS: These findings provide a framework for understanding pediatricians' decisions to recommend HPV vaccines and may be used to guide the design of interventions to maximize vaccine recommendations. PMID- 17870646 TI - Cross-cultural development of a child health care questionnaire on satisfaction, utilization, and needs. AB - OBJECTIVE: The instrument Child Health Care-Satisfaction, Utilization and Needs (CHC-SUN) has been developed cross-culturally to evaluate pediatric health care services for children with special health care needs (CSHCN) from the proxy perspective of parents. METHODS: The children of the participating parents received treatment in pediatric specialty clinics in 7 European countries for asthma, cystic fibrosis, diabetes, epilepsy, cerebral palsy, rheumatoid arthritis, and atopic dermatitis. The instrument was developed through a process including literature review, expert consensus, and item generation through focus groups. The pilot instrument was extensively tested to assess psychometric properties, support item reduction, and evaluate clinical validity. The final field version was tested in a new sample of 795 parents in 7 countries. RESULTS: Pilot testing and item reduction resulted in a practical 40-item instrument with 14 single items related to provision of services (module 1), and 26 items related to 6 scales on satisfaction with care (module 2), and 1 item on general satisfaction with care. Satisfaction with care scales showed very good psychometric properties, both initially and in the field version, with Cronbach's alpha ranging between .80 and .95 in the revised scales. Both modules discriminated well between functional status and diagnosis across countries. CONCLUSIONS: A new instrument is available to measure provision of services and satisfaction with care for children with chronic conditions from the perspective of parents. Cross-cultural analysis reveals that the measure is useful in multinational studies evaluating health services against the background of different health systems. PMID- 17870647 TI - Adverse drug events in pediatric outpatients. AB - OBJECTIVE: To determine rates and types of adverse drug events (ADEs) in the pediatric ambulatory setting. METHODS: A prospective cohort study at 6 office practices in the greater Boston area was conducted over 2-month periods. Duplicate prescription review, telephone surveys 10 days and 2 months after visit, and chart reviews were done. A 2-physician panel classified the severity, preventability, and ability to ameliorate (ie, if the severity or duration of the side effect could have been mitigated by improved communication) ADEs. RESULTS: We identified 57 preventable ADEs (rate 3%; 95% confidence intervals [CI], 3%-4%) and 226 nonpreventable ADEs (rate 13%; 95% CI, 11%-15%) in the medical care of 1788 patients. Of the ADEs, 152 (54%) were able to be ameliorated. None of the preventable ADEs were life threatening, although 8 (14%) were serious. Forty (70%) of the preventable ADEs were related to parent drug administration. Improved communication between health care providers and parents and improved communication between pharmacists and parents, whether in the office or in the pharmacy, were judged to be the prevention strategies with greatest potential. CONCLUSIONS: Patient harm from medication use was common in the pediatric ambulatory setting. Errors in home medication administration resulted in the majority of preventable ADEs. Approximately one fifth of ADEs were potentially preventable and many more were potentially able to be ameliorated. Rates of ADEs due to errors are comparable in children and adults despite less medication utilization in children. PMID- 17870648 TI - Differences in pediatric preventive care counseling by provider type. AB - OBJECTIVE: Many children in the United States do not receive advice about health behaviors and injury prevention during routine preventive care visits. We investigated the role of provider type in the probability of receiving advice. METHODS: We analyzed children aged 3 to 17 in the Medical Expenditure Panel Data 2002 to 2003 surveys who had only 1 preventive clinic or office visit in the past year. We examined whether provider type affects whether the child is advised about healthy eating, physical activity, the harmful effects of smoking in the home, proper safety restraints in a car, and use of a helmet when riding a bicycle. RESULTS: Pediatricians were more likely to advise about healthy eating (63.6% vs 46.8% for other physicians and 41.1% for nonphysicians; P < .01). They were also more likely than nonphysicians to advise about exercise (40.1% vs 22.2%), the harmful effects of parental smoking (42.4% vs 21.4%), proper safety restraints in a car (39.9% vs 20.5%), and use of a bicycle helmet (45.7% vs 20.9%). Regardless of provider type, rates of advice were low. CONCLUSION: Many pediatric providers, particularly those not trained as pediatricians, are missing opportunities to advise about health behaviors and injury prevention. PMID- 17870649 TI - Unanswered questions prompted during pediatric primary care visits. AB - OBJECTIVES: To identify the frequency, types, and perceived importance of questions prompted during primary care visits for which pediatricians have no ready answer; to characterize pediatricians' responses to them; and to determine how questions prompted while caring for children with special health care needs (CSHCN) and children without special needs (Cw/oSN) differ. METHODS: Patient visits with 35 general pediatricians were observed. Parents completed a CSHCN screener. Physicians provided details about their unanswered questions and their pursuit of answers. RESULTS: Of 890 observed visits, 170 (19.1%) prompted unanswered questions, of which 60.1% were deemed important or very important. Physicians intended to pursue answers to 49.7% of the questions but actually pursued answers for only 27.5%, citing lack of time and inadequate information resources as barriers. One hundred sixty-seven (18.8%) visits were with CSHCN. Unanswered questions arose more often with CSHCN than with Cw/oSN (28.7% vs 16.9%; odds ratio 1.98; 95% confidence interval, 1.32-2.97), particularly during well visits (34.6% vs 14.9%; odds ratio 3.24; 95% confidence interval, 1.59 6.39). CSHCN prompted more diagnosis and treatment questions than Cw/oSN. Questions prompted by CSHCN were ranked as more important but were no more likely to be pursued than those prompted by Cw/oSN. CONCLUSIONS: Unanswered questions arise during nearly 20% of pediatric primary care visits. Visits with CSHCN, particularly well visits, generate more questions than those with Cw/oSN. Answers are pursued for few unanswered questions, both overall and for CSHCN. Potential strategies to overcome barriers to answering questions include scheduling more time or more visits for CSHCN. PMID- 17870650 TI - Parental response to child's isolation during the SARS outbreak. AB - OBJECTIVES: To examine the needs, uncertainties, and experiences of parents during their child's hospitalization with highly suspected severe acute respiratory syndrome (HSS), and to identify ways to improve their psychological preparedness and communication with health care professionals and their isolated children during future infectious disease outbreaks. METHODS: Qualitative, semistructured interviews were conducted in July 2003 with parents of HSS pediatric patients. Seventeen HSS patients were hospitalized in a pediatric outpatient clinic of a major academic medical center in Hong Kong, between March 20 and May 28, 2003, during severe acute respiratory syndrome (SARS). Seven parents (41%) consented to participate in the study. RESULTS: Four major themes were identified from the interviews: 1) fear of immediate isolation and infection control procedures, 2) sources of anxiety, 3) coping, and 4) communication with children and health care professionals. CONCLUSIONS: Findings indicate a need to improve the psychological preparedness of the parents regarding the child's immediate isolation during hospitalization. Ample preparation and appropriate communication among parents, health care workers, and children might minimize fear and anxiety, sustain trust, and facilitate mutual understanding during an infectious disease outbreak. PMID- 17870651 TI - Subthalamic nucleus neuronal activity in Parkinson's disease and epilepsy subjects. AB - Activity from 113 subthalamic nucleus (STN) neurons from two epilepsy patients and 103 neurons from 9 Parkinson's disease (PD) patients undergoing DBS surgery showed no significant differences in frequencies (PD, mean 7.5+/-7.0 spikes/s (sps), epilepsy mean 7.8+/-8.5 sps) or in the coefficients of variation of mean discharge frequencies per 1s epochs. A striking relationship between mean discharge frequencies per 1 s epochs and the standard deviations for both groups were consistent with a random Poisson processes. These and similar findings call into question theories that posit increased STN activity is causal to parkinsonism. PMID- 17870652 TI - Rapidly progressive familial parkinsonism with central hypoventilation, depression and weight loss (Perry syndrome)--a literature review. AB - Autosomal dominant parkinsonism, hypoventilation, depression and weight loss (Perry syndrome) has been reported in only seven families worldwide. It is a rapidly progressive disease leading to death from respiratory insufficiency within a few years. Parkinsonism is usually mild, with bradykinesia, rigidity, rest and postural tremor, and axial signs. Response to levodopa is poor although transient response has been occasionally observed. The early signs include parkinsonism, depression and weight loss, whereas hypoventilation is a late feature. Neuropathology shows severe neuronal loss in the substantia nigra, less prominent neuronal loss in the locus coeruleus, and no or few Lewy bodies. In this review, we also propose diagnostic criteria for this condition. PMID- 17870653 TI - The McLeod syndrome without acanthocytes. AB - A 45-year-old man developed chorea, behavioural changes, moderate amyotrophy and polyneuropathy. Hypertrophic cardiomyopathy and increased serum lactate dehydrogenase and creatine kinase (CK) were found. Acanthocytes were not detected. The absence of XK protein and faintly expressed Kell antigens on erythrocytes were found. Genetic test revealed a R133X mutation of the XK gene, confirming the McLeod syndrome. After 7 years he suddenly developed delirium followed by severe hypoglycaemia, hyperthermia, rhabdomyolysis, hepatic and renal failure. Malignant arrhythmia caused death. PMID- 17870654 TI - Antimutagenic properties of a polyphenol-enriched extract derived from sesame seed perisperm. AB - A polyphenolic mixture derived from sesame-seed perisperm (SSP) strongly reduced the mutagenicity of hydrogen peroxide (H(2)O(2)), sodium azide (NaN(3)), and benzo[a]pyrene (BaP) in strains TA100 and/or TA98 of Salmonella typhimurium. It exhibited desmutagenic activity against H(2)O(2), BaP in TA98 and/or TA100 and biomutagenic activity (apparently by affecting the DNA-repair system) against NaN(3) in strain TA100. According to in vitro experiments the polyphenolic mixture inhibited the activity of the CYP1A1 (EROD) enzyme responsible for the activation of BaP in the Ames' test, as well as that of the cytosolic enzyme GST. A cytosolic fraction from liver of male Wistar rats treated with either 20% SSP in the food, or 3mg or 6 mg of polyphenolic mixture/20 g food/day for a time period of 8 weeks reduced the mutagenic potential of BaP in strains TA100 and TA98, with the cytosolic fraction from rats treated with SSP causing the strongest reduction. Furthermore, a microsomal fraction from the 20% SSP-treated rats inhibited the mutagenicity of BaP in strains TA100 (26.3%) and TA98 (23%). In contrast, a microsomal fraction from rats treated with 3mg of polyphenolic mixture stimulated the mutagenicity of BaP in TA100 but reduced it in TA98, while for the microsomal fraction from rats treated with 6 mg of polyphenolic mixture, these effects on TA100 and TA98 were reversed. PMID- 17870655 TI - Vibrational spectroscopy investigation using ab initio and density functional theory on p-anisaldehyde. AB - The FTIR and FT Raman spectra of p-anisaldehyde has been recorded in the regions 4,000-400 and 3,500-100 cm(-1), respectively. The optimized geometry, frequency and intensity of the vibrational bands of p-anisaldehyde were obtained by ab initio and DFT levels of theory with complete relaxation in the potential energy surface using 6-31G(d,p) basis set. A complete vibrational assignment aided by the theoretical harmonic frequency analysis has been proposed. The harmonic vibrational frequencies calculated have been compared with experimental FTIR and FT Raman spectra. The observed and the calculated frequencies are found to be in good agreement. The experimental spectra also coincide satisfactorily with those of theoretically constructed bar type spectrograms. PMID- 17870656 TI - Fluorescence quenching of CdSe quantum dots by nitroaromatic explosives and their relative compounds. AB - CdSe quantum dots (QDs) were synthesized in oleic acid and octadecene medium under high-temperature and dispersed in chloroform. Nitroaromatic explosives and their relative compounds, 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (DNT), nitrobenzene (NB), 2,4-dinitrochlorobenzene (DNBCl) and p-nitrotoluene (NT) can obviously cause the fluorescence quenching of the synthesized QDs. Under the optimum conditions, a nonlinear response was observed over the concentration range of 10(-8) to 10(-5) M for them all. The modified Stern-Volmer quenching equations of ln I(0)/I versus C show a good linear relation in 10(-5) M order of magnitude, and the detection limits approach 10(-6) to 10(-7) M. PMID- 17870657 TI - Synthesis, growth, structural, spectroscopic and optical studies of a new semiorganic nonlinear optical crystal: L-valine hydrochloride. AB - Single crystals of a new semiorganic nonlinear optical (NLO) material, L-valine hydrochloride (LVHCl), having dimensions up to 20 mm x 6 mm x 4 mm have been grown by slow evaporation solution growth technique. Single crystal X-ray diffraction studies confirm that the grown crystal belongs to the monoclinic system. The functional groups presented in the crystal were confirmed by Fourier transform infrared (FTIR) technique. Optical transmission spectrum shows very low absorption in the entire visible region. Differential thermal and thermogravimetric analyses confirmed that the crystal is stable up to 211 degrees C. The powder second harmonic generation (SHG) efficiency of LVHCl is 1.7 times efficient as potassium dihydrogen phosphate (KDP). PMID- 17870658 TI - Experimental problems in Raman spectroscopy applied to pigment identification in mixtures. AB - Raman spectroscopy provides useful information to detect and identify pictorial materials in artworks, although some problems are involved when the identification of individual pigments in mixtures is treated. With the hypothesis of the Principle of superposition, the mixture spectrum should be the direct sum of each pondered individual spectrum. In this work, we will show several mixtures where it can be noticed that the mixture spectrum is not qualitatively proportional to the sum of pondered individual spectra. Also there were some cases where the bands of one of the pigments could not be detected in the mixture spectrum. This non-linear behaviour could be attributed to specific proprieties of each material that are revealed when they interact with each other. We conjecture that, for instance, the different reflectances or the wavelength of the laser source could be determinant factors of the obtained results. In this paper an experimental method has been designed in order to characterize the quantitative behaviour of the Raman bands corresponding to each pigment in a mixture. Adequate coefficients are defined and calculated to facilitate the study of the spectral contribution of the different components of a mixture. PMID- 17870659 TI - Development of a case-based system for grouping diagnoses in general practice. AB - INTRODUCTION: This article describes the development of EPICON; an application to group ICPC-coded diagnoses from electronic medical records in general practice into episodes of care. These episodes can be used to estimate prevalence and incidence rates. METHODS: We used data from 89 practices that participated in the Dutch National Survey of General Practice. Additionally, we held interviews with seven experts, and studied documentation to establish the requirements of the application and to develop the design. We then performed a formative evaluation by assessing incorrectly grouped diagnoses. RESULTS: EPICON is based on a combination of logical expressions, a decision table, and information extracted from individual cases by case-based reasoning. EPICON is able to group all diagnoses in the selected 89 practices, and groups 95% correctly. CONCLUSION: The results cautiously indicate that EPICONs performance will probably be adequate for the purpose of estimating morbidity rates in general practice. PMID- 17870660 TI - Diagnosis and epidemiological studies of human metapneumovirus using real-time PCR. AB - BACKGROUND: Human metapneumovirus (hMPV) is prevalent in children, the elderly and immunocompromised individuals, but available epidemiological data is limited. OBJECTIVES: (1) To develop and validate a real-time PCR method for hMPV diagnosis. (2) To determine the percentage of hMPV in respiratory specimens from the community and its association with outbreaks in our geographic area. (3) To provide epidemiological data in terms of age distribution, seasonality and co infections. STUDY DESIGN: A real-time PCR assay was designed for detection of hMPV lineages A and B. Prospective testing for hMPV over a 22-month period was then undertaken. RESULTS: The real-time PCR was sensitive and specific for detection of both lineages of hMPV. hMPV was detected in 9.5% (n=8239) of the specimens and 25% of the outbreaks (n=100) tested. The hMPV-positive patients ranged in age from 18 days to 99 years with a median age of 24 months. The number of positive samples peaked during the winter months of December, January and February. A high rate of co-infections was noted in the samples tested. CONCLUSIONS: hMPV is common in the community and is associated with outbreaks. Including hMPV in routine testing improves etiological diagnosis of acute respiratory infections. PMID- 17870661 TI - Aircraft noise: effects on macro- and microstructure of sleep. AB - OBJECTIVE: The effects of aircraft noise on sleep macrostructure (Rechtschaffen and Kales) and microstructure (American Sleep Disorders Association [ASDA] arousal criteria) were investigated. PATIENTS AND METHODS: For each of 10 subjects (mean age 35.3 years, 5 males), a baseline night without aircraft noise (control), and two nights with exposure to 64 noise events with a maximum sound pressure level (SPL) of either 45 or 65 dBA were chosen. Spontaneous and noise induced alterations during sleep classified as arousals (ARS), changes to lighter sleep stages (CSS), awakenings including changes to sleep stage 1 (AS1), and awakenings (AWR) were analyzed. RESULTS: The number of events per night increased in the order AWR, AS1, CSS, and ARS under control conditions as well as under the two noise conditions. Furthermore, probabilities for sleep disruptions increased with increasing noise level. ARS were observed about fourfold compared to AWR, irrespective of control or noise condition. CONCLUSIONS: Under the conditions investigated, different sleep parameters show different sensitivities, but also different specificities for noise-induced sleep disturbances. We conclude that most information on sleep disturbances can be achieved by investigating robust classic parameters like AWR or AS1, although ASDA electroencephalographic (EEG) arousals might add relevant information in situations with low maximum SPLs, chronic sleep deprivation or chronic exposure. PMID- 17870662 TI - Sleep-related laryngospasm caused by gastroesophageal reflux. AB - Gastroesophageal reflux is a suspected cause of sleep-related laryngospasm [Thurnheer R, Henz A, Knoblauch A. Sleep-related laryngospasm. Eur Respir J 1997;10:2084-6], but the relationship has not been directly documented by polysomnography (PSG). We report the case of an eight-year-old girl with asthma who was referred for evaluation of awakenings with respiratory distress. The description of her events included stridorous breathing suggestive of laryngospasm. A PSG was performed with esophageal pH monitoring, and during the recording pH dropped below four on nine occasions. Following two of the pH drops, acute respiratory distress with stridor was documented in video and audio recording, supporting a causal relationship between sleep-related gastroesophageal reflux and laryngospasm. PMID- 17870663 TI - Pediatric environmental medicine in Eastern Central Europe. AB - Pediatric environmental medicine in Central Eastern Europe needs support and development on national, institutional and individual basis. This situation is quantitatively, but not fundamentally different from what is to be found in Central Europe. PMID- 17870665 TI - German Environmental Survey for Children (GerES IV)--first results. AB - German Environmental Surveys (GerESs) are large scale population studies which have been carried out on adults in 1985/86, 1990/92 and 1998 and on children aged 6-14 years in 1990/92. GerES IV is the first survey focussing exclusively on children [Becker, K., Schulz, C., Babisch, W., Durkop, J., Roskamp, E., Seiwert, M., Szewzyk, R., Ullrich, D., Seifert, B., 2005. German Environmental Survey for Children (GerES IV) 2003-2006. Pullut. Atmos. 188, 475-479]. GerES IV included a representative sample of 1790 children aged 3-14 of the participants of the National Health Interview and Examination Survey on Children and Adolescents. The primary goal of GerES IV is not only to analyse and document the extent, distribution and determinants of German children's exposure to environmental pollutants but to discover links between environmental exposure and health. Results will help develop preventive measures and advance further research. They might provide the basis for environmental and public health policy decisions. Precondition to achieve this task is a description of the data on exposures and the data on health outcomes. This work is currently performed at the Federal Environment Agency. First results show a remarkable decrease of the blood lead level of German children aged 6-14 years from 32.3 microg/l in 1990/92 (GerES II) to 16.3 microg/l in GerES IV which is the lowest mean lead concentration determined in German studies so far. None of the children had a value exceeding 100 microg/l. In GerES IV, the following health-related issues will be primarily examined: the relationship between sensitisation against mould spores and the occurrence of mould in households, irritation of eyes and respiratory system caused by formaldehyde, other aldehydes, or total volatile organic compounds (TVOC); the impact of non-occupational noise on hearing loss, stress and sleep disturbances, and the connection between contact allergies, nickel and scents. 9.5% of the children showed a sensitisation to at least one of the moulds examined (Penicillium (notatum) chrysogenum, Aspergillus versicolor, Wallemia sebi, Eurotium spp., Alternaria alternata). The most frequent sensitisation was against Penicillium chrysogenum. GerES IV might broaden the knowledge in terms of environmental causes of health outcomes. Children of smoking mothers showed higher mean cotinine concentrations than children living with a smoking father, regardless whether they smoked daily or occasionally. Results from the GerES IV pilot study showed a relation between environmental tobacco smoke (ETS) exposure and an increased susceptibility to infections and inflammations of the middle ear. PMID- 17870664 TI - Some evidence of effects of environmental chemicals on the endocrine system in children. AB - Pollutant chemicals that are widespread in the environment can affect endocrine function in laboratory experiments and in wildlife. Although human beings are commonly exposed to such pollutant chemicals, the exposures are generally low and clear effects on endocrine function from such exposures have been difficult to demonstrate. Human data including both exposure to the chemical agent and the endocrine outcome are reviewed here, including age at weaning, age at puberty, anogenital distance, and sex ratio at birth, and the strength of the evidence are discussed. Although endocrine disruption in humans by pollutant chemicals remains largely undemonstrated, the underlying science is sound and the potential for such effects is real. PMID- 17870666 TI - Family structures as environmental risk to children's development. AB - Demographic developments - birth rates are sharply declining in most European countries - have the effect that in very many families children are growing up without brothers or sisters, often with one parent only. This may lead to a lack of social experiences and skills in the next generation. PMID- 17870667 TI - Perfluorooctane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) in human breast milk: results of a pilot study. AB - Perfluorinated compounds (PFC) are a large group of chemicals produced for several decades and widely used for many industrial and consumer applications. Because of their global occurrence in different environmental media, their persistence and their potential to bioaccumulate in organisms they are of toxicological and public concern. In the present study, perfluorooctane sulphonate (PFOS) and perfluorooctanoic acid (PFOA) were quantified in 70 breast milk samples. Samples were obtained from Leipzig, Germany (38 archived samples), Munich, Germany (19 fresh samples) and Gyor, Hungary (13 frozen samples). PFOS could be quantified in all 70 samples. The concentration in samples from Germany ranged between 28 and 309 ng/l (median: 119 ng/l). Samples from Hungary showed significantly higher PFOS concentrations (median 330 ng/l, range 96-639 ng/l). In only 11 of 70 samples (16%) PFOA reached the LOQ (200 ng/l); values ranged from 201 to 460 ng/l. If only those samples with PFOA values above the LOQ were considered, we found a significant correlation between the PFOS and PFOA concentrations (r=0.75, p=0.008). Based on the results of the German sample, we estimated an intake of 0.10 microg PFOS/day (using median) or 0.27 PFOS microg/day (using maximum value) via breast milk for an infant of 5 kg bodyweight. Our data suggest that fully breastfed infants are unlikely to exceed the recommended tolerable daily intake of PFC. However, more target-oriented studies are needed to identify the amount and time-trend of PFOS and PFOA in maternal blood during pregnancy, after delivery, as well as in the growing infant and in its diet (e.g., breast milk and formula). PMID- 17870668 TI - Molecular identification of coliform bacteria isolated from drinking water reservoirs with traditional methods and the Colilert-18 system. AB - The accuracy of a traditional method (lactose utilization with acid and gas production) for the detection of coliform bacteria and E. coli was tested in comparison with method ISO 9308-1 (based on acid formation from lactose) and the Colilert-18 system (detection of beta-galactosidase). A total of 345 isolates were identified after isolation from water samples using API 20E strips. The Colilert-18 led to the highest number of positive findings (95% of the isolates were assigned to coliforms), whereas the ISO-9308-1 method resulted only in 29% coliform findings. With the traditional method only 15% were rated positive. Most of the isolates were identified by the API 20E system as Enterobacter spp. (species of the Enterobacter cloacae complex), Serratia spp., Citrobacter spp.and Klebsiella spp.; but species identification remained vague in several cases. A more detailed identification of 126 pure cultures by using 16S rRNA gene sequence analysis and analysis of the hsp60 gene resulted in the identification of Enterobacter nimipressuralis, E. amnigenus, E. asburiae, E. hormaechei, and Serratia fonticola as predominat coliforms. These species are beta-galactosidase positive, but show acid formation from lactose often after a prolonged incubation time. They are often not of fecal origin and may interfere with the ability to accurately detect coliforms of fecal origin. PMID- 17870669 TI - Hospital-acquired legionellosis originating from a cooling tower during a period of thermal inversion. AB - A case of hospital-acquired legionellosis occurred in a 75-year-old male patient who underwent surgery due to malignant melanoma. Legionellosis was proven by culture of Legionella pneumophila serogroup 1 from bronchoalveolar lavage (BAL) fluid. Being a chronic smoker the patient used to visit the sickroom balcony that was located about 90 m to the west of a hospital cooling tower. Routine cooling tower water samples drawn during the presumed incubation period revealed 1.0x10(4) CFU/100 ml (L. pneumophila serogroup 1). One of three isolates from the cooling tower water matched the patient's isolate by monoclonal antibody (mab)- and genotyping (sequence-based typing). Horizontal transport of cooling tower aerosols probably was favoured by meteorological conditions with thermal inversion. The case report stresses the importance of routine maintenance and microbiological control of hospital cooling towers. PMID- 17870670 TI - Genetic aspects of tendinopathy. AB - Tendinopathy is characterised by a disorganised, haphazard healing response with no histological signs of inflammation. Research on tendon injuries is limited to the description of the condition and its management, and the pathogenesis is still ill defined. Together with known intrinsic and extrinsic factors, genetics may play a significant role in the aetiopathogenesis of tendinopathy. ABO and other closely linked genes, COL5A1, and tenascin-C have all been implicated in the aetiopathogenesis of tendinopathy. However, the precise role of these genes in causing or protecting individuals from developing tendinopathy is yet to be defined. An interaction between the various intrinsic and extrinsic factors with the genetic make-up of an individual may increase the likelihood of one individual developing tendinopathy over another. Tendinopathy may well be polygenic, involving complex interactions between multiple genes, and could possibly run in families. Further investigations should determine the exact role played by genetic influences in maintaining tendon homeostasis and pave the way for gene transfer therapy to be developed for the management of tendinopathies. PMID- 17870672 TI - Unmet mental health needs in pediatric epilepsy: insights from providers. AB - Eighteen pediatric neurologists and 18 pediatricians completed a 5-point Likert scale questionnaire on their knowledge of, attitudes toward, and management of the behavioral, cognitive, and psychosocial aspects of pediatric epilepsy, before and after a lecture on this topic. They also responded to questions about possible barriers to mental health care of children with epilepsy. The brief educational intervention modified the knowledge/attitudes of pediatricians compared with pediatric neurologists on the impact of epilepsy on behavior and cognition in children with epilepsy. However, there were no between-group differences in how providers perceived their competence to assess behavioral and cognitive comorbid conditions in pediatric epilepsy. Responses to open-ended questions suggested insufficient mental health coverage for and expertise on pediatric epilepsy, resistance of mental health clinicians to treat children with epilepsy, and the stigma of mental health as possible barriers to mental health care in children with epilepsy. In addition to the need for provider education about the behavioral and cognitive comorbid conditions of pediatric epilepsy, these findings emphasize the importance of examining alternative routes to increasing mental health care for children with epilepsy. PMID- 17870671 TI - Clinical and serological features of patients with autoantibodies to GW/P bodies. AB - GW bodies (GWBs) are unique cytoplasmic structures involved in messenger RNA (mRNA) processing and RNA interference (RNAi). GWBs contain mRNA, components of the RNA-induced silencing complex (RISC), microRNA (miRNA), Argonaute proteins, the Ge-1/Hedls protein and other enzymes involving mRNA degradation. The objective of this study was to identify the target GWB autoantigens reactive with 55 sera from patients with anti-GWB autoantibodies and to identify clinical features associated with these antibodies. Analysis by addressable laser bead immunoassay (ALBIA) and immunoprecipitation of recombinant proteins indicated that autoantibodies in this cohort of anti-GWB sera were directed against Ge 1/Hedls (58%), GW182 (40%) and Ago2 (16%). GWB autoantibodies targeted epitopes that included the N-terminus of Ago2 and the nuclear localization signal (NLS) containing region of Ge-1/Hedls. Clinical data were available on 42 patients of which 39 were female and the mean age was 61 years. The most common clinical presentations were neurological symptoms (i.e. ataxia, motor and sensory neuropathy) (33%), Sjogren's syndrome (SjS) (31%) and the remainder had a variety of other diagnoses that included systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and primary biliary cirrhosis (PBC). Moreover, 44% of patients with anti-GWB antibodies had reactivity to Ro52. These studies indicate that Ge-1 is a common target of anti-GWB sera and the majority of patients in a GWB cohort had SjS and neurological disease. PMID- 17870673 TI - The cell biology of intervertebral disc aging and degeneration. AB - Intervertebral disc degeneration, which mimics disc aging but occurs at an accelerated rate, is considered to be related to neck or low back pain and disc herniation. Degenerated discs show breakdown of the extracellular matrix and thus fail to bear the daily loadings exerted on the spine. Rather than a passive process of wear and tear, disc degeneration is an aberrant, cell-mediated response to progressive structural failure due to aging and other environmental factors such as abnormal mechanical stress. With aging and degeneration, disc cells undergo substantially biologic changes, including alternation of cell type in the nucleus pulposus, increased cell density but decreased number of viable cells as a result of increased cell death and increased cell proliferation, increased cell senescence, and altered cell phenotype which is characterized by compromised capability of synthesizing correct matrix components and by enhanced catabolic metabolism. These changes are involved in the process of disc degeneration through the complicated interactions among them. To retard or reverse disc degeneration, the abnormal conditions of the decreased viable cell population and the altered cell phenotype should be corrected. As potential therapies for disc degeneration, intradiscal protein injection, gene transfer and cell implantation are being understudied in vivo. Suppression of excessive apoptosis and accelerated senescence of disc cells may be other choices for treating disc degeneration. When performing a biologic therapy in order to repair or regenerate the degenerated disc, nutrient and biomechanical factors should also be incorporated, because they are the major causes of the biologic changes experienced by disc cells. Moreover, a very early intervention is indicated by the finding that the onset of human disc degeneration occurs as early as by adolescence. PMID- 17870674 TI - Base excision repair enzyme endonuclease III suppresses mutagenesis caused by 8 hydroxy-dGTP. AB - To examine whether base excision repair suppresses mutations induced by oxidized deoxyribonucleotide 5'-triphosphates in the nucleotide pool, 8-hydroxy-dGTP (8-OH dGTP) and 2-hydroxy-dATP were introduced into Escherichia coli strains deficient in endonucleases III (Nth) and VIII (Nei) and MutY, and mutations in the chromosomal rpoB gene were analyzed. The spontaneous rpoB mutant frequency was also examined in mutT/nth and mutT/nei strains, to assess the influence on the mutations induced by the endogenous 8-OH-dGTP accumulated in the mutT mutant. The mutations induced by exogenous 2-hydroxy-dATP were similar in all of the strains tested. Exogenous 8-OH-dGTP increased the rpoB mutant frequency more efficiently in the nth strain than that in the wild-type strain. The spontaneous mutant frequency in the mutT/nth strain was 2-fold higher than that in the mutT strain. These results suggest that E. coli endonuclease III also acts as a defense against the mutations caused by 8-OH-dGTP in the nucleotide pool. PMID- 17870675 TI - Quantification of zidovudine and its monophosphate in cell extracts by on-line solid-phase extraction coupled to liquid chromatography. AB - A simple and rapid analytical method for the simultaneous quantification of zidovudine (AZT) and its monophosphate (AZTMP) in cell extracts has been developed using high-performance liquid chromatography (HPLC) with on-line solid phase extraction and 2-aminoethyl-3'-azido-2',3'-dideoxythymidin-5'-yl phosphodiester sodium salt as internal standard (IS). The cell extract samples were directly injected on a short reversed-phase precolumn using an aqueous buffer containing an ion-pairing reagent as a mobile phase. Under these conditions, the analytes were retained on the precolumn whereas the proteins were discarded. The analytes were then transferred onto the analytical column by increasing the strength of the eluent. The calibration curve was linear over a concentration range of 0.5-100 microg/ml. Inter- and intra-day accuracy and precision results satisfied the accepted criteria for bioanalytical validation. This method was used to study the decomposition pathway of a model pronucleotide in an in vitro approach. PMID- 17870676 TI - New monolithic enzymatic micro-reactor for the fast production and purification of oligogalacturonides. AB - Fast production and purification of alpha-(1,4)-oligogalacturonides was investigated using a new enzymatic reactor composed of a monolithic matrix. Pectin lyase from Aspergillus japonicus (Sigma) was immobilized on CIM-disk epoxy monolith. Studies were performed on free pectin lyase and immobilized pectin lyase to compare the optimum temperature, optimum pH, and thermal stability. It was determined that optimum temperature for free pectin lyase and immobilized pectin lyase on monolithic support is 30 degrees C, and optimum pH is 5. Monolithic CIM-disk chromatography is one of the fastest liquid chromatographic method used for separation and purification of biomolecules due to high mass transfer rate. In this context, online one step production and purification of oligogalacturonides was investigated associating CIM-disk pectin lyase and CIM disk DEAE. This efficient enzymatic bioreactor production of uronic oligosaccharides from polygalacturonic acid (PGA) constitutes an original fast process to generate bioactive oligouronides. PMID- 17870677 TI - SPE/SPME-GC/MS approach for measuring musk compounds in serum and breast milk. AB - Musks can be used to provide distinctive odor or scent in many personal care products. Musk compounds have received growing attention in recent years by environmental scientists and regulatory agencies because of their increasing production volume and widespread environmental presence. A combined separation approach using solid phase extraction (SPE) and solid phase micro extraction (SPME) coupled to detection by gas chromatography mass spectrometry was developed for measuring four polycyclic musk compounds (Galactoside, Tonalide, Muskene, Celestolide) in serum and milk. The SPE and SPME separation steps were fully automated and required minimal sample handling. The method, which requires only 1 mL serum or breast milk to achieve limits of detection of 0.03-0.3 ng/mL, is applicable in biomonitoring studies for human internal dose measurement of polycyclic musk compounds. PMID- 17870678 TI - Determination of aesculin in rat plasma by high performance liquid chromatography method and its application to pharmacokinetics studies. AB - A sensitive and reproducible high performance liquid chromatography method with UV detection was described for the determination of aesculin in rat plasma. After deproteinization by methanol using metronidazole as internal standard (I.S.), solutes were evaporated to dryness at 40 degrees C under a gentle stream of nitrogen. The residue was reconstituted in 100 microl of mobile phase and a volume of 20 microl was injected into the HPLC for analysis. Solutes were separated on a Diamonsil C18 column (250 mm x 4.6 mm i.d., 5 microm particle size, Dikma) protected by a ODS guard column (10 mm x 4.0 mm i.d., 5 microm particle size), using acetonitrile-0.1% triethylamine solution (adjusted to pH 3.0 using phosphoric acid) (10:90, v/v) as mobile phase (flow-rate 1.0 ml/min), and wavelength of the UV detector was set at 338 nm. No interference from any endogenous substances was observed during the elution of aesculin and internal standard (I.S., metronidazole). The retention times for I.S and aesculin were 10.4 and 12.4 min, respectively. The limit of quantification was evaluated to be 57.4 ng/ml and the limit of detection was 24.0 ng/ml. The method was used in the study of pharmacokinetics of aesculin after intraperitoneal injection (i.p.) administration in rats. PMID- 17872325 TI - [Cognitive and psycho-affective modification]. PMID- 17872326 TI - [Consciousness: a psychoanalytical point of view]. AB - There is no specific point of view on consciousness from psychoanalytic theory. Psychoanalytic investigations are focused on inconscious psychic acts and the ways they can be accessible to consciousness. We successively examine the virtual preconscious, the repressed preconscious, and the proper unconscious. For each of these types of events stored in memory, we specify the modes of access into consciousness, specifically the role of co-thinking in the access to consciousness proper and the status of the unconscious psychic reality. PMID- 17872327 TI - [Multidimensional Self, autobiographical memory and aging]. AB - Nowadays, several psychological fields are interested in the Self-concept and then propose their own definitions and assessment methods. The Self is considered as a cognitive system and is structurally composed of a set of multidimensional episodic and semantic personal representations. While it could be either the agent or the object of consciousness, the Self is at the origin of the subjective identity and feeling of continuity across the time. In the present review, we aimed at introducing the concept of Self focusing on its links with autobiographical memory and to expose the research about the impact of aging on the Self, distinguishing between its structural (Self-knowledge) and functional (Self-consciousness) dimensions. The results from the literature and our own research group suggest that the Self characteristics are not equally changed by aging, the functional dimensions being more specially involved. PMID- 17872328 TI - [Dementia complex due to HIV disease and aging]. AB - The epidemiology of human immunodeficiency virus (HIV) infection has changed in recent years. New infections in persons over the age of 50 have increased and seropositive individuals are aging due to the widespread use of highly active antiretroviral therapies in Western countries. HIV-associated dementia remains one of the commonest neurological disorders associated with AIDS, but its progression has been modified by HAART and immune reconstitution. We review in details the epidemiology, pathogenesis, clinical features, diagnosis, and management of the HIV dementia and related cognitive disorders, and their relationship with aging. PMID- 17872329 TI - [Diversity of the psychopathology of memory complaints in the aging adult]. AB - A strong correlation was frequently observed between memory complaints and the scores obtained on anxiety and depression scales. This paper contributes to explore the psychopathological basis of the experience of decreased memory efficiency. Our research, based on a clinical psychopathological methodology, rests upon semi-directed interviews associated with a psychological examination combining neuropsychological tests and projective methodology. The population consists of 31 subjects aged 53 to 85 years, who presented with memory complaint upon their own initiative in a memory clinic and for whom the neuropsychological examination ruled out the hypothesis of the onset of cerebral deterioration. The patients exhibited more or less mild neurotic, borderline and narcissistic psychic modes of functioning. There was no patient exhibiting psychotic functioning. We have been able to verify among the neurotic patients how the emphasis of anxiety of memory loss correspond to a revival of the anxiety of castration, that of being dispossessed of capacities which guarantee autonomy, judgement, power of decision and action. Furthermore, in the contemporary context of cerebral pathologies which can transform every intelligent man in a dependent, indeed bedridden being, this complaint jointly betrays an anxiety triggered by the risk of a violated intimacy due to the care which could be given as well as an anxiety linked to eviction, dispossession and to acts of mistreatment which are greatly apprehended. In patients exhibiting borderline functioning, the complaint of memory decline betrayed anxiety of fracture and dissolution of the self, and of lack of object-support. In narcissistic patients, the weakness of memory mobilisation eradicated the illusion that time does not pass, does not cause damage and that objects neither leave nor die. PMID- 17872330 TI - [Does the care for the fear of falling bring a profit to community living elderly people who had experienced falls?]. AB - INTRODUCTION: fall is common in old people and has multiple consequences, physical but also psychological, with a fear of falling which results in reduction in the activities of everyday life, loss of autonomy and entry in dependence. The aim of the study was to evluate the benefit of taking into account the fear of falling in the care of old people who had experienced falls. METHODOLOGY: old people who experienced falls and with a good cognitive status were followed in a day hospital during one year. Evaluation including a specific assessment of the responsibility of the psychological factor, the photolangage, was performed before and after multi-field rehabilitation. We used the rating scales ADL, IADL, SF-36, SAFE, and verbal and analogical scales of the fear of falling. RESULTS: fifteen patients were included (mean age 85 years +/- 5,7). The majority were women living alone, with a good nutritional status, a moderated renal insufficiency, and a comorbidity involving polymedication. Scores on the ADL and IADL scales showed a consolidation of the patients' autonomy, with a slight but significant improvement of the IADL scores (p < 0,05). All scales assessing the fear of falling (visual analogical, verbal scales, SAFE) showed a statistically significant improvement (p<0,001). SF-36 scale, exploring the quality of life perceived by the patients, showed a great deterioration immediately after falling, and a statistically significant improvement on seven of the eight subscales after rehabilitation. The global physical score (GCV) was improved in a nonsignificant way, whereas the global psychic score (MCS) progressed in a statistically significant way (p < 0,001). CONCLUSION: this pilot study shows that multi-field rehabilitation and adapted assumption of responsibility of fear of falling brings a benefit in term of quality of life and preservation of autonomy in old people living in the community who had experienced falls. PMID- 17872331 TI - [Assessment of memories for public events in Parkinson's disease]. AB - Many patients with Parkinson's disease (PD) have subtle cognitive impairment which often contribute to explain their cognitive complaint. In the literature, neuropsychological studies showed few difficulties for memory and executive functions. We report the performance of 12 PD patients and 12 controls subjects for public events memory. On a 30-item French scale battery (EVE-30), their scores were lower than those of the controls in 4 tasks: evocation, questions, datation and date recognition. They also had difficulties to perform a chronological classification of 8 events. No difference was found between PD patients and control subjects in the events recognition task. Flash bulb memories (FBM) were less frequent in PD patients than in control subjects: 23% versus 34% of cases. A correlation was observed between the scores on the EVE total scale, questions scale, FBM scale and the score on the anterograde recall. Scores on the EVE total scale, questions scale were correlated to the scores on the executive function (initiation) scale. PD patients without dementia seemed to have a low cognitive impairment of retrograde public event memory for episodic and semantic components. Specific difficulties were observed for date evocation and recognition, and chronological classification. These very global deficits to recuperate information can be related to the striatal dopamine depletion which affects the prefrontal functions. PMID- 17872332 TI - [Endoplasmic reticulum stress--common pathomechanism of different diseases?]. AB - The endoplasmic reticulum (ER) is a dominant metabolic compartment in the maintenance of intracellular homeostasis and plays a decisive role in adaptation to changes of the extra- and intracellular environment. Various stressors (e.g. disturbances of intracellular calcium balance, hypoglycaemia, hypoxia, altered redox homeostasis, virus infection) affect the protein folding in the ER lumen, resulting in an accumulation of unfolded proteins. They cause the activation of ER specific signaling pathways called unfolded protein response (UPR). Activated UPR pathways have been demonstrated in various diseases the etiology of which is totally different (diabetes, neurodegenerative diseases, hepatitis etc), therefore, UPR represents a common pathomechanism. Understanding of ER stress related events can open new perspectives to improve the current therapy. PMID- 17872333 TI - [The state of the colorectal screening in Hungary: lessons of the pilot programs]. AB - In Hungary, colorectal cancer is the second most common malignant disease. Due to its natural history, colorectal cancer is particularly suitable for screening. At present, epidemiological evidences of the effectiveness of detection of the symptomless colorectal cancer and its precursors are only available for the demonstration of fecal occult blood, endoscopic methods are also in use. For mass screening, fecal occult blood tests are recommended. Guaiac-type chemical methods are widely criticized because of the lack of specificity. Out of the emerging technologies, immunochemical methods based on the antigenicity of blood proteins (hemoglobin) seem to be the most suitable. In the model programmes organized in the frame of the National Public Health Programme, an immunochemical method using two blood proteins (hemoglobin and albumin) have been used. The compliance was not more than 30-45%. About one-third of those with positive blood test refused colonoscopy. The programmes revealed a great number of adenomatous polyps and early cancers, and in the way, the effectiveness of the method has been proved. The model programmes are still continued. Before the continuous and gradual extension of colorectal screening, the validity of the specific method needs to be tested and proved in order to be recognized as a routine procedure for screening. There is a need to test the feasibility of total colonoscopy, however, to this effect the colonoscopic capacity in the country has to be further developed. PMID- 17872334 TI - [Genetic background of esophageal squamous cell carcinoma]. AB - Esophageal cancer is the 9th most frequent malignancy. In more than 90% of all patients with esophageal cancer, the tumour is detected in an advanced stage. Surgery, conventional chemo- and radiotherapy are relatively ineffective. Gene therapy came into the limelight of interest. Authors discuss the genetics, molecular pathogenesis of esophageal squamous carcinoma. Clinical experience in connection with gene therapy of esophageal squamous cell carcinoma is discussed. Different targets include complementary nucleic acid treatment (antisense therapy), gene-replacement and importance of small interfering RNA-s. PMID- 17872335 TI - [Nephrogenic systemic fibrosis]. AB - The nephrogenic systemic fibrosis - referred to in the literature earlier as nephrogenic fibrotizing dermopathy - is a rare clinical entity that develops in patients with renal disease. Its development has been described mainly after the usage of a gadolinium-based MRI contrast medium in patients with impaired renal function, mainly in dialysed patients. The nephrogenic systemic fibrosis is characterized by fibrosis evolving in the distal part of the extremities, and in more severe cases involving the lung, the liver, heart and skeletal muscles. The disease may have a fast progression and fatal outcome if it involves multiple organ systems, in approximately 5% of the cases. Until now, no evidence-based therapy of nephrogenic systemic fibrosis is known, however, in single cases an amelioration has been described after renal transplantation and plasmapheresis, and remission has been described after extracorporal photopheresis. PMID- 17872336 TI - [Successful alemtuzumab treatment of a patient with atypical hairy cell leukaemia variant]. AB - Although hairy cell leukaemia and hairy cell leukaemia variant are characterized by much alike clinical features, these two diseases are disparate in nature and treatment. While hairy cell leukaemia responds quite well to 2 chlorodeoxyadenosine (cladribine) treatment, hairy cell leukaemia variant has much worse response rate and has no effective treatment option yet. With other treatment modalities, including monoclonal antibody treatment, we have less experience. Alemtuzumab (Campath-1H, MabCampath) treatment has been reported in a case with hairy cell leukaemia in relaps while there is no data with alemtuzumab therapy in the treatment of hairy cell leukaemia variant. The authors present their case of a 58 year-old male who has been diagnosed with hairy cell leukaemia variant upon clinical findings and lymphocyte phenotyping. Alemtuzumab treatment was started (3 x 30 mg/week s.c. for 12 weeks). After 8 weeks of treatment haematologic remission was achieved; flow cytometry has revealed only 1.5% malignant cells. Alemtuzumab treatment can be favourable in those cases of hairy cell leukaemia and hairy cell leukaemia variant which is dominated mainly by bone marrow infiltration and present no lymphadenomegaly or splenomegaly. In our case the p53 mutation had no influence on the outcome of alemtuzumab treatment. PMID- 17872337 TI - [Editors-in-chief of Orvosi Hetilap in the art of numismatics]. PMID- 17872344 TI - Exenatide therapy in obese patients with type 2 diabetes mellitus treated with insulin. AB - OBJECTIVE: To evaluate the effect of exenatide on clinical parameters in obese patients with type 2 diabetes mellitus whose hyperglycemia is not adequately controlled despite treatment with oral hypoglycemic agents and insulin. METHODS: In this retrospective analysis, clinical progress of 52 obese patients with type 2 diabetes treated with exenatide, 5 mcg twice daily, in an outpatient setting was reviewed. Treatment initiation was between September and December 2005. Mean follow-up period was 26 weeks. Thirty-eight patients took exenatide regularly (Group A); 14 patients discontinued exenatide because of insurance, personal, or economic reasons (Group B). Measurements at baseline and at follow-up included body weight; blood pressure; and levels of hemoglobin A1c (HbA1c), high sensitivity C-reactive protein (CRP), and plasma lipids. Insulin dosage requirements were assessed. RESULTS: Mean body weight (+/- standard error of the mean) decreased by 6.46 +/- 0.8 kg (P<.001) in Group A and increased by 2.4 +/- 0.6 kg in Group B (P<001). In Group A, mean HbA1c decreased by 0.6 +/- 0.21% (P = .007), and the insulin dosage requirement decreased for rapid-acting and mixed insulins (P<.02). In Group A, means of the following parameters decreased: serum total cholesterol by 8.5 +/- 3.3% (P = .03), triglycerides by 26 +/- 7.6% (P = .01), systolic blood pressure by 9.2 +/- 3.3 mm Hg (P = .02), and high sensitivity CRP by 34 +/- 14.3% (P = .05). These indices did not change in Group B. CONCLUSION: Exenatide effectively treats obese patients with type 2 diabetes on insulin, leading to weight loss and reduction in levels of HbA1c, systolic blood pressure, triglycerides, and high-sensitivity CRP. PMID- 17872345 TI - Associations of thyroid-stimulating hormone and free thyroxine concentrations with health and life satisfaction in elderly adults. AB - OBJECTIVE: To analyze associations between thyroid-stimulating hormone (TSH) and free thyroxine (FT4 concentrations and life satisfaction, symptoms, self-rated health, and common neuropsychiatric diseases (depression or dementia) in a community-dwelling elderly population to provide evidence whether to decrease the upper reference limit for TSH or the optimal TSH target in levothyroxine treatment in older adults. METHODS: In this cross-sectional study, we determined TSH and FT4 concentrations in a thyroid disease-free population of 502 men (median age, 71 years) and 584 women (median age, 73 years) and in a patient group of 49 women (median age, 75 years) with primary hypothyroidism who were stable users of thyroxine treatment. Life satisfaction, self-rated health, depression, and dementia were assessed with specific questions and with tools such as the Self-report Depression Scale and the Mini-Mental State Examination. Independent variables were dichotomized, and associations of these variables with TSH and FT4 levels were assessed in the thyroid disease-free population. Levels of TSH and FT4 in thyroid disease-free women and in women treated with thyroxine were also compared. RESULTS: After age adjustment, there were no associations between TSH levels and self-rated health, life satisfaction, or most symptoms in the thyroid disease-free population. No associations were found between diagnosed depression or Mini-Mental State Examination results and levels of TSH and FT4. Dementia was associated with higher FT4 concentration in men. Although women treated with thyroxine had TSH levels that were higher than thyroid disease-free women, there were no statistically significant differences in independent variables between these 2 groups. CONCLUSION: Our results do not support the need to decrease the upper reference limit for TSH or to lower the optimal TSH target in levothyroxine treatment in older adults, as recommended in recent guidelines. PMID- 17872346 TI - Clinical and bone density outcomes of tumor-induced osteomalacia after treatment. AB - OBJECTIVE: To report the outcomes of tumor-induced osteomalacia after treatment, particularly related to recovery of bone mass. METHODS: We review the clinical course of a 61-year-old man extremely debilitated from multiple fractures and neuromuscular weakness due to tumor-induced osteomalacia and report the changes in biochemical markers and bone density after removal of the causative neoplasm. RESULTS: At the time of diagnosis, the patient's serum phosphorus and 1,25 dihydroxyvitamin D levels were depressed, and his fibroblast growth factor-23 level was markedly elevated. These values normalized 2 days after surgery and remained within their respective reference ranges 4 and 12 months after resection of a mesenchymal tumor. Lumbar bone density values (T-scores) were 0.445 g/cm2 ( 5.9) preoperatively, 0.939 g/cm2 (-1.4) 4 months after surgery, and 1.152 g/cm2 (0.7) 12 months after surgery. Left femoral neck values at the same time points were 0.525 g/cm2 (-3.0), 1.035 g/cm2 (-0.8), and 1.184 g/cm2 (1.9). Ultra-distal radius values at the same time points were 0.128 g/cm2 (-7.0), 0.191 g/cm2 ( 5.9), and 0.259 g/cm2 (-4.8). In addition, he recovered neuromuscular function and was able to leave his wheelchair. CONCLUSION: Tumor-induced osteomalacia can be an extremely debilitating disease. With successful localization, identification, and resection of the neoplasm, bone mass and physical function can recover. PMID- 17872347 TI - Transformation of a pituitary macroadenoma into to a corticotropin-secreting carcinoma over 16 years. AB - OBJECTIVE: To describe a case of a pituitary macroadenoma that differentiated into a corticotropin (ACTH)-secreting carcinoma with metastasis to the thigh. METHODS: We present a case report with a 16-year follow-up that includes anatomic and endocrine documentation of the history of an ACTH-secreting carcinoma. RESULTS: A 32-year-old woman presented for evaluation in 1989 because of visual field defects. Magnetic resonance imaging revealed a locally invasive 3-cm macroadenoma. She had no clinical signs of cortisol excess. The patient underwent surgical debulking followed by a course of radiation directed to the pituitary. Results from retrospective immunohistochemical staining with antibodies against ACTH, prolactin, and MIB-1 were negative. Postoperatively, she could not be weaned from exogenous steroids without developing symptoms of adrenal insufficiency. In 1995, she developed left facial palsy and diplopia caused by tumor growth. In 1997, the patient developed progressive symptoms of cortisol excess, which continued after exogenous steroid replacement was discontinued. The patient's clinical status continued to deteriorate because of local mass effect from tumor growth and uncontrolled hypercortisolism. She underwent bilateral adrenalectomy in 2003. The patient remained debilitated in a long-term care facility for 2 years when she was found to have a mass on her left hip. Biopsy results of the obturator muscle revealed metastatic tumor of neuroendocrine origin with strong reactivity to ACTH antibodies and MIB-1 labeling in 8% of tumor cell nuclei. CONCLUSION: A pituitary tumor can transform into an ACTH secreting carcinoma in an indolent manner. Patients with invasive pituitary adenomas require long-term surveillance to monitor for differentiation into pituitary carcinoma. PMID- 17872348 TI - Ovarian hilus-cell hyperplasia and high serum testosterone in a patient with postmenopausal virilization. AB - OBJECTIVE: To describe a woman with postmenopausal virilization and hirsutism caused by hilus-cell hyperplasia. METHODS: We present a case report including laboratory, radiographic, and pathologic findings in a patient with postmenopausal hirsutism and virilization caused by ovarian hilus-cell hyperplasia as well as a brief review of the literature. RESULTS: A 60-year-old postmenopausal woman presented with extensive hirsutism, male-pattern hair loss, and clitoromegaly. The patient's plasma testosterone levels were very high, but computed tomography showed the adrenal glands to be normal in size. Pelvic ultrasonography revealed a cystic lesion in the left ovary. After bilateral salpingo-oophorectomy, histologic examination demonstrated a diffuse pattern of hilus-cell hyperplasia in the ovarian hilum. CONCLUSION: In the differential diagnosis of postmenopausal virilization, hilus-cell hyperplasia, although rare, should be considered. PMID- 17872349 TI - Two cases of thyroid storm-associated cholestatic jaundice. AB - OBJECTIVE: To describe the association of the rare and serious complication of jaundice with severe thyrotoxicosis, a potentially lethal endocrine disorder. METHODS: We report the clinical, laboratory, and pathologic findings of 2 cases of severe jaundice (total bilirubin levels: 35.2 mg/dL in case 1 and 42 mg/dL in case 2) associated with thyroid storm in the absence of a history of liver disease, thionamide exposure, or congestive heart failure. We also present other relevant reports available in the literature. RESULTS: Case 1 was a 38-year-old woman who presented with nausea, vomiting, fatigue, pruritus, and frequent nonbloody diarrhea. She was transferred to our institution because of worsening hyperbilirubinemia. Case 2 was a 35-year-old woman admitted to a community hospital with thyroid storm and jaundice. Upon transfer to our institution, the patient was unconscious, mechanically ventilated, and in atrial fibrillation. In case 2, liver biopsy results revealed diffuse hepatocellular ballooning with intrahepatic cholestasis with mild portal lymphocytic infiltration. Both patients presented with severe cholestatic jaundice in the absence of congestive heart failure; underlying liver disease (infectious or autoimmune); or previous exposure to thionamides, other hepatotoxic agents, or complementary and alternative medications. In both cases, jaundice responded to therapy with antithyroid medications. Both patients eventually underwent thyroidectomy with complete resolution of the jaundice. CONCLUSION: The data strongly suggest that in these patients, the hepatic dysfunction was primarily due to hyperthyroidism. These cases indicate that the mere presence of hyperbilirubinemia during severe thyrotoxicosis should not per se delay the use of potentially life-saving thionamides once a thorough evaluation for other causes of liver disease has been completed. PMID- 17872350 TI - Idiopathic hypertrophic pachymeningitis resulting in delayed panhypopituitarism. AB - OBJECTIVE: To describe an adult man with idiopathic hypertrophic pachymeningitis (IHPM) that progressed to involve the pituitary gland and caused hypopituitarism 6 years after the onset of the first symptom. METHODS: We describe the slow 6 year progression of IHPM in a man being treated with steroids, radiation, and antineoplastic medications and present clinical, pathologic, and imaging data. The pertinent literature is also reviewed. RESULTS: A 35-year-old man who presented with headaches, pain, and sensory loss on the right side of his face had thickened, inflamed dura without granulomas. Initially, the right middle fossa, the lateral wall of the right cavernous sinus, and the tentorium were involved. Results from a dural biopsy specimen were consistent with IHPM. His symptoms were only partially controlled with continuous high-dose steroids, cyclophosphamide, azathioprine, and radiation therapy. IHPM was diagnosed based on findings from an open brain biopsy. Other pathologic causes of inflammatory dural thickening were excluded. Six years after the onset of the first clinical manifestation of IHPM, the patient developed panhypopituitarism. Magnetic resonance imaging showed that the inflammatory process had invaded the pituitary gland. IHPM was confirmed by findings from transsphenoidal biopsy. CONCLUSION: IHPM is a rare disorder characterized by an unexplained inflammatory thickening of the dura at the skull base. The usual clinical symptoms are intractable headache and cranial nerve palsies. Physicians must be aware that IHPM can be slowly progressive despite attempted treatment, and that the disease process can invade the sella with dysfunction of both the anterior and the posterior pituitary gland. PMID- 17872351 TI - Idiopathic hypoparathyroidism presenting with severe hypocalcemia and asymptomatic basal ganglia calcification followed by acute intracerebral bleed. AB - OBJECTIVE: To report a case of idiopathic hypoparathyroidism presenting with severe hypocalcemia and intracerebral calcifications that resulted in a spontaneous intracerebral bleed. METHODS: We present the clinical, laboratory, and radiologic findings in a woman with idiopathic hypoparathyroidism who developed spontaneous intracerebral bleed in the setting of chronic intracerebral calcifications. RESULTS: A 37-year-old woman presented with vague symptoms of hypocalcemia. Clinical evaluation revealed brisk deep tendon reflexes and positive Chvostek's and Trousseau's signs. The serum calcium level was 3.7 mg/dL (reference range, 8.0 to 10.6 mg/dL) and the phosphorus level was 8.2 mg/dL (reference range, 2.3 to 5.0 mg/dL). Serum intact parathyroid hormone was undetectable. Computed tomography of the head showed extensive bilateral symmetrical calcification of basal ganglia and dentate nucleus in the cerebellum and centrum semiovale. Fluid and electrolytes were replaced appropriately, and calcium and calcitriol were prescribed. While in the hospital, the patient developed an acute intracerebral bleed confirmed by computed tomography. The patient recovered without neurologic sequelae and was discharged from the hospital on calcium supplementation and calcitriol. Repeated computed tomography of the head 3 years later demonstrated complete resolution of the bleed. CONCLUSION: This case suggests that patients with severe hypoparathyroidism and intracerebral calcification may be at risk for spontaneous intracerebral bleed and should be monitored accordingly. PMID- 17872352 TI - Malignant pheochromocytoma of the organ of Zuckerkandl requiring aortic and vena caval reconstruction. AB - OBJECTIVE: To describe a case of a malignant pheochromocytoma located in the organ of Zuckerkandl that required aortic and vena caval resection and reconstruction. METHODS: We present a case report that includes clinical, laboratory, and radiographic data as well as photographs, results from pathology, and a brief review of the literature. RESULTS: A 46-year-old man was referred for evaluation of a 1.4-cm left adrenal mass incidentally discovered on an abdominopelvic computed tomography (CT) scan. Subsequent laboratory evaluation revealed the following values: urine norepinephrine, 252 microg/24 h; urine normetanephrine, 1122 microg/24 h; urine metanephrine, 162 microg/24 h; urine epinephrine, 7 microg/24 h; urine vanillylmandelic acid, 8 mg/24 h; and plasma metanephrine, 98 pg/ mL. Imaging characteristics of the left adrenal mass were consistent with a benign adenoma, but CT also demonstrated a hypervascular para aortic mass. 123I-metaiodo-benzylguanidine scanning with fusion CT imaging demonstrated increased radiopharmaceutical uptake within the para-aortic mass consistent with a paraganglioma in the organ of Zuckerkandl. Findings from CT angiography of the abdomen and pelvis suggested aortic involvement and vena caval thrombus. The mass was excised en bloc, including portions of the aorta, inferior vena cava, and right ureter. The aorta and vena cava were reconstructed using Dacron grafts. The remaining right ureter and kidney were removed to avoid the possibility of a urine leak from an ureteroureterostomy. Final pathologic and operative findings confirmed a malignant pheochromocytoma of the organ of Zuckerkandl with invasion into the wall of the inferior vena cava and tumor thrombus extending into the lumen. CONCLUSION: Malignant pheochromocytoma of the organ of Zuckerkandl involving the aorta and inferior vena cava is exceedingly rare, and although surgical resection and reconstruction can be radical and aggressive, this treatment offers the only chance for cure. PMID- 17872353 TI - Management of low-risk differentiated thyroid cancer. AB - OBJECTIVE: To summarize the definitions of and management recommendations for low risk thyroid cancer made by the American and European Thyroid Associations and synthesize this information with the recent literature, including systematic evaluations of tumor staging systems guiding therapy. METHODS: The American Thyroid Association and European Thyroid Association guidelines were compared and pertinent literature since 2005 was reviewed. RESULTS: Of papillary thyroid microcarcinomas (PTMC), up to 50% breach the thyroid capsule, 64% have lymph node metastases, up to 43% are multifocal, and as many as 2.8% have distant metastases. Locoregional and distant recurrences are, respectively, as high as 5.9% and 1.5%. As many as 1 in 4 patients with a papillary thyroid carcinoma 1.5 cm or smaller develop persistent disease. Cancer-related mortality rates are usually less than 1%, but are as high as 2% in some reports. Tumor staging systems are too inaccurate to guide therapy. CONCLUSION: It is unlikely that many patients will forgo treatment after understanding their risk, especially when total thyroidectomy and radioiodine (131I) therapy can reduce the PTMC recurrence or persistence disease rate to zero. Preoperatively diagnosed PTMC should be treated with total or near-total thyroidectomy, regardless of tumor size. For very low-risk patients with unifocal PTMC smaller than 1 cm that is removed by chance during surgery to treat benign thyroid disease, lobectomy alone without 131I therapy may be sufficient therapy if there are no concerning histologic features and no tumor extension beyond the thyroid, metastases, history of head and neck irradiation, or positive family history--any of which requires total or near-total thyroidectomy and remnant ablation with 30 mCi. PMID- 17872354 TI - Consensus and controversy regarding osteoporosis in the pediatric population. AB - OBJECTIVE: To review current consensus and controversy surrounding the diagnosis and treatment of osteoporosis in childhood and adolescence. METHODS: The medical literature was reviewed with emphasis on the importance of early skeletal health, risk factors for bone fragility, and the diagnosis and management of children at risk for osteoporosis. RESULTS: Childhood and adolescence are critical periods for optimizing bone growth and mineral accrual. Bone strength is determined by bone size, geometry, quality, and mass-variables that are influenced by genetic factors, activity, nutrition, and hormones. For children with genetic skeletal disorders or chronic disease, bone growth and mineral accrual may be compromised, increasing the lifetime risk of osteoporosis. The goal for the clinician is to identify children at greatest risk for future fragility fracture. Bone densitometry and turnover markers are challenging to interpret in children. Prevention and treatment of bone fragility in children are less well established than in adults. Optimizing nutrition and activity may not restore bone health, but the drug armamentarium is limited. Sex steroid replacement has not proven effective in restoring bone mass in patients with anorexia nervosa or exercise associated amenorrhea. Bisphosphonates can increase bone mass and may reduce bone pain and fractures, most convincingly in patients with osteogenesis imperfecta. Further studies are needed to establish the safety, efficacy, and optimal drug, duration, and dosage in pediatric patients. CONCLUSION: Bone health during the first 2 decades contributes to the lifetime risk of osteoporosis. Further research is needed to develop evidence-based recommendations for the diagnosis and treatment of osteoporosis in childhood. PMID- 17872355 TI - Management of patients with low-risk papillary thyroid carcinoma. AB - OBJECTIVE: To define a rational, cost-effective, simple approach to managing most patients with papillary thyroid cancer (PTC) who are at low-risk of either cause specific mortality or tumor recurrence. METHODS: Taking advantage of the collective experience of a cohort of 2512 patients with PTC who had initial definitive treatment at the Mayo Clinic in Rochester, Minnesota, between 1940 and 2000, a 5-step approach to the management of low-risk PTC has been devised. This program is based on appropriate preoperative ultrasound localization of neck disease and potentially curative surgery consisting of near-total or total thyroidectomy, with appropriate neck nodal exploration and resection. RESULTS: The emphasis of the present program is on the extent of initial surgery, where optimal care is ascribed to a near-total thyroidectomy with curative intent and appropriate neck nodal resection as predicated by appropriate preoperative ultrasonography evaluation of regional lymph nodes. Radioiodine remnant ablation (RRA) is not applicable to patients with PTC who are defined on the day of definitive initial surgery to be at low risk as defined by a metastasis, age, completeness of resection, invasion, and size (MACIS) score of less than 6. CONCLUSION: The outlook for patients with low-risk PTC is very optimistic, with rates at 30 postoperative years of only 1% for cause-specific mortality and less than 15% for tumor recurrence at any site. The long-term results obtained by potentially curative bilateral resection, appropriate regional lymph nodal excision, and selective use of RRA are excellent. Realistically improving these acceptably low rates for cause-specific mortality and tumor recurrence may be difficult. PMID- 17872356 TI - Applications of molecular biology and genetics in endocrinology. AB - OBJECTIVE: To review the growing impact of molecular biology and genetics on clinical endocrinology. METHODS: Medical literature, databases, and Web sites describing genetics and genomic medicine with relevance for clinical endocrinology were reviewed. RESULTS: Many monogenic disorders can now be explained at the molecular level and the diagnosis can be established through mutational analysis. The ability to establish a molecular diagnosis is relevant for carrier detection and genetic counseling. In contrast to the significant advances in monogenic disorders, the current knowledge about the genetic components contributing to the pathogenesis of complex disorders is still relatively modest and is a major focus of current research efforts. Molecular biology already has an important impact on therapy in endocrine disorders. A broad spectrum of recombinant peptides and proteins are used in daily practice, eg, insulin and insulin analogues. Moreover, the increasingly detailed understanding of the molecular pathogenesis of cancer is leading to the development of novel and more specific inhibitors. While genetic testing has many advantages, it is important that physicians and patients are aware of potential limitations. They include, among others, technical limitations and allelic and nonallelic heterogeneity. These limitations need to be discussed in detail with patients and relatives, and it is often useful to involve a genetic counselor before obtaining informed consent by the individuals undergoing testing. CONCLUSION: Molecular biology and genetics play an increasingly important role for the diagnosis and therapy of endocrine disorders. Challenges for the future include the elucidation of the genetic components contributing to complex disorders, eg, diabetes mellitus type 2, and the development of cheaper and comprehensive DNA sequencing technologies. Lastly, it is important that there is continuing attention directed towards the ethical, social, and legal aspects surrounding genetic medicine. PMID- 17872357 TI - Current controversy related to glucocorticoid and insulin therapy in the intensive care unit. AB - OBJECTIVE: To review the controversy related to the widespread use of intensive insulin treatment (IIT) to maintain normoglycemia and of glucocorticoid replacement therapy in patients with sepsis in the intensive care unit (ICU). METHODS: We performed a MEDLINE search of the literature using a combination of words (critical/intensive care, endocrinology/endocrine, glucocorticoid/adrenal, insulin) to identify original studies and reviews on glucocorticoid therapy and IIT in the ICU. RESULTS: Glucocorticoid replacement therapy is advocated for patients with sepsis who have relative adrenal insufficiency. The current definition of relative adrenal insufficiency is poorly supported, and validated endocrine criteria that consistently identify ICU patients likely to benefit from glucocorticoid therapy are not yet available. IIT benefits postoperative patients at high risk of infection and patients who remain in the ICU more than 3 days. Potential harm caused by early IIT administration in medical ICU patients remains controversial. The role of early nutritional supplementation in major studies about IIT is largely unexplored. Improvements in insulin infusion protocols are needed to reduce the risk of hypoglycemia related to IIT. CONCLUSION: Endocrine therapy in the ICU is entering a new era. Controversies remain related to glucocorticoid and insulin therapy even as interest in new, and old, endocrine therapies is being revived. PMID- 17872358 TI - Clinical manifestations and current treatment options for diabetic neuropathies. AB - OBJECTIVE: To review the clinical manifestations and current treatment options for diabetic neuropathies, one of the most common complications of diabetes mellitus. METHODS: We performed a MEDLINE search of the English-language literature using a combination of words (diabetic neuropathy, diabetic autonomic neuropathy, diagnosis and treatment) to identify original studies, consensus statements, and reviews on diabetic neuropathies published in the past 25 years. Emphasis was placed on clinical manifestations of distal polyneuropathy and its treatment, especially new therapies. RESULTS: Distal symmetric polyneuropathy, the most common form of diabetic neuropathy, usually involves small and large nerve fibers. Small-nerve fiber neuropathy often presents with pain and loss of intraepidermal nerve fibers, but without objective signs or electrophysiologic evidence of nerve damage. This type of neuropathy is a component of impaired glucose tolerance and the metabolic syndrome. The greatest risk from small-fiber neuropathy is foot ulceration and subsequent gangrene and amputation. Large-nerve fiber neuropathy produces numbness, ataxia, and incoordination, thus impairing activities of daily living and causing falls and fractures. Successfully treating diabetic neuropathy requires addressing the underlying pathogenic mechanisms, treating symptoms to improve quality of life, and preventing progression and complications of diabetes mellitus. Two new drugs, duloxetine hydrochloride and pregabalin, have recently been approved for treatment of neuropathic pain associated with diabetes mellitus. CONCLUSION: Symptomatic therapy has become available and newer and better treatment modalities, based on etiologic factors, are being explored with potential for clinically significant reduction of morbidity and mortality. Preventive strategies and patient and physician education still remain key factors in reducing complication rates and mortality. PMID- 17872359 TI - Adrenocortical carcinoma presenting as a retroperitoneal abscess: an unusual presentation of a rare tumor. PMID- 17872360 TI - Comment on the AACE/AME medical guidelines for the diagnosis and management of thyroid nodules. PMID- 17872361 TI - Chaotic stirring in quasi-turbulent flows. AB - Transport in laminar flows is governed by chaotic stirring and striation in long thin filaments. In turbulent flows, isotropic mixing dominates and tracers behave like stochastic variables. In this paper, we investigate the quasi-turbulent, intermediate regime where both chaotic stirring and turbulent mixing coexist. In these flows, the most common in nature, aperiodic Lagrangian coherent structures (LCSs) delineate particle transport and chaotic stirring. We review the recent developments in LCS theory and apply these techniques to measured surface currents in Monterey Bay, California. In the bay, LCSs can be used to optimize the release of drifting buoys or to minimize the impact of a coastal pollution source. PMID- 17872362 TI - alpha-Synuclein and Parkinson disease susceptibility. AB - BACKGROUND: Mutations in the alpha-synuclein (SNCA) gene have been shown to be responsible for a rare familial form of Parkinson disease (PD). Furthermore, polymorphic variants in multiple regions of the gene have been associated with susceptibility to idiopathic PD in different populations. OBJECTIVE: To evaluate and to confirm the role of SNCA variants in PD pathogenesis. METHODS: We included 667 subjects (397 cases with idiopathic PD and 270 healthy, ethnically matched controls) of Northern Central and Southeastern European origin. We analyzed genotypes at 14 markers spanning the SNCA locus and its major haplotype blocks and conducted a haplotype analysis for four promoter markers including the microsatellite marker Rep1. RESULTS: The three single nucleotide polymorphisms (SNPs) of the promoter region (rs2583988, rs2619364, rs2619363) and a SNP in the 3'UTR (rs356165) of the SNCA gene showed the greatest evidence for an association with PD (p or= 0.74, r (2) >or= 0.29). The promoter haplotype "261-T-G T" (Rep1-rs2583988-rs2619364-rs2619363) was associated with disease (p = 0.032). The most significant association with PD was generated by excluding Rep1 (p = 0.008). This association remained significant when analyzing the Serbian patients separately and was of borderline significance for the German patients. CONCLUSIONS: Our findings confirm that genetic variability within the SNCA locus is associated with susceptibility to idiopathic Parkinson disease (PD). We found evidence for disease association with single nucleotide polymorphisms at both the 5' and the 3' end of the gene with pairwise linkage disequilibrium between them. The association was independent of the Rep1 status, and one major SNCA promoter haplotype class seems to be associated with PD susceptibility. PMID- 17872363 TI - Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations. AB - BACKGROUND: Peripheral nerve hyperexcitability (PNH) is characterized by muscle overactivity due to spontaneous discharges of lower motor neurons usually associated with antibodies against voltage-gated potassium channels. PNH may also occur in combination with episodic ataxia or epilepsy caused by mutations in K(V)1.1 or K(V)7.2 channels. Only one PNH-associated mutation has been described so far in K(V)7.2 (R207W), in a family with both PNH and neonatal seizures. METHODS: PNH was characterized by video and electromyography. The KCNQ2 gene was sequenced and K(V)7.2 channels were functionally characterized using two microelectrode voltage-clamping in Xenopus oocytes. RESULTS: In a patient with PNH without other neurologic symptoms, we identified a novel KCNQ2 mutation predicting loss of a charged residue within the voltage sensor of K(V)7.2 (R207Q). Functional analysis of both PNH-associated mutants revealed large depolarizing shifts of the conductance-voltage relationships and marked slowing of the activation time course compared to wild type (WT) channels, less pronounced for R207Q than R207W. Co-expression of both mutant with WT channels revealed a dominant negative effect reducing the relative current amplitudes after short depolarizations by >70%. The anticonvulsant retigabine, an activator of neuronal K(V)7 channels, reversed the depolarizing shift. CONCLUSIONS: Mutations in KCNQ2 can cause idiopathic PNH alone and should be considered in sporadic cases. Both K(V)7.2 mutants produce PNH by changing voltage-dependent activation with a dominant negative effect on the WT channel. This distinguishes them from all hitherto examined Kv7.2 or K(V)7.3 mutations which cause neonatal seizures by haploinsufficiency. Retigabine may be beneficial in treating PNH. PMID- 17872364 TI - Postwithdrawal rebound increase in T2 lesional activity in natalizumab-treated MS patients. PMID- 17872365 TI - Chorionic gonadotropin beta-subunit gene expression in the marmoset pituitary is controlled by steroidogenic factor 1, early growth response protein 1, and pituitary homeobox factor 1. AB - In most mammals, the gonads are under the control of the pituitary gonadotropins LH and FSH. However, in the common marmoset monkey Callithrix jacchus, no LH is detectable in the pituitary but chorionic gonadotropin (CG) instead, normally produced in the placenta. This study investigated the mechanism of CGbeta subunit activation in the pituitary and why humans do not express CG in the pituitary. 5' Rapid amplification of cDNA ends, EMSA, and promoter-driven luciferase assays performed with the gonadotropic LbetaT2 cells showed that marmoset monkey CGbeta is GnRH responsive and activated similar to human LHbeta by the transcription factors steroidogenic factor 1 (SF1), early growth response protein 1 (Egr1), and pituitary homeobox factor 1 (Pitx1) and displayed a transcriptional start site 7 bp upstream of exon 1. In contrast, the human CGbeta promoter displayed in the binding elements for pituitary homeobox factor 1 and early growth response protein 1 three consensus sequence mismatches, leading to very low activity that could be drastically increased by mutation to the consensus sequences. Vice versa, marmoset CGbeta promoter activity was reduced after introduction of the human CGbeta mismatches. An in vivo study in pregnant marmoset monkeys showed that during pregnancy, there is no significant decrease of pituitary CG production, contrasting human LH down-regulation. In conclusion, pituitary CG production is lacking in humans due to the absence of appropriate DNA-binding elements, which are present in marmosets, thereby enabling GnRH activation of expression. However, during pregnancy of marmosets, pituitary CG expression is not inhibited. PMID- 17872366 TI - Leptin sensitivity in the developing rat hypothalamus. AB - In adults, the adipocyte-derived hormone, leptin, regulates food intake and body weight principally via the hypothalamic arcuate nucleus (ARC). During early postnatal development, leptin functions to promote the outgrowth of neuronal projections from the ARC, whereas a selective insensitivity to the effects of leptin on food intake appears to exist. To investigate the mechanisms underlying the inability of leptin to regulate food intake during early development, leptin signaling was analyzed both in vitro using primary cultures of rat embryonic ARC neurones and in vivo by challenging early postnatal rats with leptin. In neuronal cultures, despite the presence of key components of the leptin signaling pathway, no detectable activation of either signal transducer and activator of transcription 3 or the MAPK pathways by leptin was detected. However, leptin down regulated mRNA levels of proopiomelanocortin and neuropeptide Y and decreased somatostatin secretion. Leptin challenge in vivo at postnatal d (P) 7, P14, P21, and P28 revealed that, in contrast to adult and P28 rats, mRNA levels of neuropeptide Y, proopiomelanocortin, agouti-related peptide and cocaine- and amphetamine-regulated transcript were largely unaffected at P7, P14, and P21. Furthermore, leptin stimulation increased the suppressor of cytokine signaling-3 mRNA levels at P14, P21, and P28 in several hypothalamic nuclei but not at P7, indicating that selective leptin insensitivity in the hypothalamus is coupled to developmental shifts in leptin receptor signaling. Thus, the present study defines the onset of leptin sensitivity in the regulation of energy homeostasis in the developing hypothalamus. PMID- 17872367 TI - Age-related alterations in pituitary and testicular functions in long-lived growth hormone receptor gene-disrupted mice. AB - The somatotropic axis, GH, and IGF-I interact with the hypothalamic-pituitary gonadal axis in health and disease. GH-resistant GH receptor-disrupted knockout (GHRKO) male mice are fertile but exhibit delayed puberty and decreases in plasma FSH levels, testicular content of LH, and prolactin (PRL) receptors, whereas PRL levels are elevated. Because the lifespan of GHRKO mice is much greater than the lifespan of their normal siblings, it was of interest to compare age-related changes in the hypothalamic-pituitary-gonadal axis in GHRKO and normal animals. Plasma IGF-I, insulin, PRL, LH, FSH, androstenedione and testosterone levels, and acute responses to GnRH and LH were measured in young (2-4 and 5-6 months of age) and old (18-19 and 23-26 months of age) male GHRKO mice and their normal siblings. Plasma IGF-I was not detectable in GHRKO mice. Plasma PRL levels increased with age in normal mice but declined in GHRKO males, and did not differ in old GHRKO and normal animals. Plasma LH responses to acute GnRH stimulation were attenuated in GHRKO mice but increased with age only in normal mice. Plasma FSH levels were decreased in GHRKO mice regardless of age. Plasma testosterone responses to LH stimulation were attenuated in old mice regardless of genotype, whereas plasma androstenedione responses were reduced with age only in GHRKO mice. Testicular IGF-I mRNA levels were normal in young and increased in old GHRKO mice, whereas testicular concentrations and total IGF-I levels were decreased in these animals. These findings indicate that GH resistance due to targeted disruption of the GH receptor gene in mice leads to suppression of testicular IGF-I levels, and modifies the effects of aging on plasma PRL levels and responses of the pituitary and testes to GnRH and LH stimulation. Plasma testosterone levels declined during aging in normal but not in GHRKO mice, and the age-related increase in the LH responses to exogenous GnRH was absent in GHRKO mice, perhaps reflecting a delay of aging in these remarkably long-lived animals. PMID- 17872368 TI - Tumor necrosis factor-alpha-induced anterior pituitary folliculostellate TtT/GF cell uncoupling is mediated by connexin 43 dephosphorylation. AB - The anterior pituitary folliculostellate (FS) cells are key elements of the paracrine control of the pituitary function. These cells are the source and the target of growth factors and cytokines, and are connected to other pituitary cells via Cx43-mediated gap junctions. Here, we show that acute treatment of the FS TtT/GF cell line with TNF-alpha caused a transient cell uncoupling that was accompanied by the dephosphorylation of Cx43 in Ser368. These TNF-alpha-evoked effects were dependent on protein phosphatase 2A (PP2A) and protein kinase C (PKC) activities. TNF-alpha did not affect total cell Cx43-PP2A catalytic subunit interaction, but it did induce PP2A catalytic subunit recruitment to the Triton X 100 insoluble subcellular fraction, in which Cx43-gap junction plaques are recovered. This recruitment temporally coincided with Cx43 phosphorylated in Ser368-Cx43 dephosphorylation. Cx43 did not interact with the conventional PKC alpha, but it did interact with the atypical PKC-zeta. Moreover, this interaction was weakened by TNF-alpha. Cx43 dephosphorylation in Ser368 was followed by the tyrosine phosphorylation of the protein. The temporary closure of gap junctions during acute TNF-alpha challenge may constitute a protective mechanism to limit or confine the spread of inflammatory signals among the FS cells. PMID- 17872369 TI - Role of luteal glucocorticoid metabolism during maternal recognition of pregnancy in women. AB - The human corpus luteum (hCL) is an active, transient, and dynamic endocrine gland. It will experience extensive tissue and vascular remodeling followed by 1) demise of the whole gland without any apparent scarring or 2) maintenance of structural and functional integrity dependent on conceptus-derived human chorionic gonadotropin (hCG). Because cortisol has well-characterized roles in tissue remodeling and repair, we hypothesized that it may have a role in controlling luteal dissolution during luteolysis and would be locally produced toward the end of the luteal cycle. Glucocorticoid-metabolizing enzymes [11beta hydroxysteroid dehydrogenase (11betaHSD) types 1 and 2] and the glucocorticoid receptor (GR) were assessed in hCL and cultures of luteinized granulosa cells (LGC) using immunofluorescence and quantitative RT-PCR. Furthermore, the effect of cortisol on steroidogenic cell survival and fibroblast-like cell activity was explored in vitro. The hCL expressed 11betaHSD isoenzymes in LGC and nuclear GR in several cell types. hCG up-regulated the expression and activity of 11betaHSD type 1 (P < 0.05) and down-regulated type 2 enzyme (P < 0.05) in vitro and tended to do the same in vivo. Cortisol increased the survival of LGC treated with RU486 (P < 0.05) and suppressed the activity of a proteolytic enzyme associated with luteolysis in fibroblast-like cells (P < 0.05). Our results suggest that, rather than during luteolysis, it is luteal rescue with hCG that is associated with increased local cortisol generation by 11betaHSD type 1. Locally generated cortisol may therefore act on the hCL through GR to have a luteotropic role in the regulation of luteal tissue remodeling during maternal recognition of pregnancy. PMID- 17872370 TI - Neonatal lipopolysaccharide exposure exacerbates stress-induced suppression of luteinizing hormone pulse frequency in adulthood. AB - Early life exposure to immunological challenge has programming effects on the adult hypothalamo-pituitary-adrenocortical axis stress responsivity, and stress is known to suppress GnRH pulse generator activity, especially LH pulses. We investigated the effects of neonatal exposure to endotoxin on stress-induced suppression of pulsatile LH secretion and the involvement of corticotropin releasing factor (CRF) receptor mechanisms in adult rats. Pups at 3 and 5 d of age were administered lipopolysaccharide (LPS, 50 microg/kg, ip). At 12 wk of age, they were ovariectomized and implanted with sc 17beta-estradiol capsules and i.v. cannulas. Blood samples (25 microl) were collected every 5 min for 5 h for LH measurement. After 2 h of sampling, rats were given LPS (25 microg/kg, iv). CRF and CRF-R1 and CRF-R2 receptor mRNA was determined by RT-PCR in medial preoptic area (mPOA) micropunches collected at 3 h after LPS administration. There was no difference in basal LH pulse frequency between neonatal LPS- and neonatal saline-treated controls. However, neonatal endotoxin-treated rats exhibited a significantly greater LPS stress-induced suppression of LH pulse frequency. Basal mPOA CRF-R1 expression was unchanged in neonatal LPS- and neonatal saline-treated rats. However, CRF-R1 expression was significantly increased in response to LPS stress in neonatal LPS-treated animals but not in neonatal saline-treated controls. CRF and CRF-R2 expression was unchanged in all treatment groups. These data demonstrate that exposure to bacterial endotoxin in early neonatal life programs long-term sensitization of the GnRH pulse generator to the inhibitory influence of stress in adulthood, an effect that might involve up-regulation of CRF-R1 expression in the mPOA. PMID- 17872371 TI - Immunocytochemical and phylogenetic analyses of an arginine vasotocin-dependent aquaporin, AQP-h2K, specifically expressed in the kidney of the tree frog, Hyla japonica. AB - Water movement occurs across the plasma membrane of various cells of animals, plants, and microorganisms through specialized water-channel proteins called aquaporins (AQPs). We have identified a new member of the amphibian AQP family, AQP-h2K, from the kidneys of Hyla japonica. This protein consists of 280 amino acid residues with two NPA (Asn-Pro-Ala) sequence motifs and a mercury-sensitive cysteine residue just upstream from the second NPA motif. There are two putative N-linked glycosylation sites at Asn-120 and Asn-128 and one protein kinase A phosphorylation site at Ser-262. The AQP-h2K protein was specifically expressed in the apical membrane and/or cytoplasm of principal cells in the kidney collecting ducts. After stimulation with arginine vasotocin, it was translocated from the cytoplasmic pool to the apical membrane. Phylogenetic analysis of AQP proteins from anurans and mammals identified six clusters of anuran AQPs: types 1, 2, 3, and 5 and two anuran-specific types, designated a1 and a2. The cluster AQPa2 contains Hyla AQP-h2 and AQP-h3, which are expressed in the anuran urinary bladder and ventral pelvic skin. AQP-h2K belongs to the type 2, together with mammalian (human and mouse) AQP2, suggesting that AQP-h2K is an anuran ortholog of the neurohypophysial hormone-regulated mammalian AQP2 and that the AQP2 molecule is already present in the anuran mesonephros. PMID- 17872372 TI - Prolactin/Leptin interactions in the control of food intake in rats. AB - Recent evidence suggests that the peptide hormone prolactin (PRL) modulates energy balance through a number of mechanisms, including acting in the brain to increase food intake. In the current studies, we first demonstrated that chronic infusions of PRL into the lateral ventricles increased food intake in cycling rats without disrupting estrous cyclicity. In subsequent experiments the hypothesis that at least part of PRL's ability to increase food intake resulted from PRL-induced leptin resistance was tested. Female rats given chronic infusions of PRL (5 microg/h) into the cerebral ventricles for 10 d did not show a reduction in food intake or body weight after a central injection of 4 microg murine leptin, whereas the expected reduction in both of these parameters was seen in vehicle-infused rats. Leptin injections were without effect on these parameters, whether they were administered to free feeding PRL-infused rats or after 24-h food deprivation. This lack of a behavioral response to leptin was accompanied by an attenuation in Fos induction and phosphorylation of signal transducer and activator of transcription 3 after leptin administration in PRL infused rats in both the ventromedial hypothalamus and paraventricular hypothalamic nucleus. PMID- 17872373 TI - Expression of G protein-coupled receptor-30, a G protein-coupled membrane estrogen receptor, in oxytocin neurons of the rat paraventricular and supraoptic nuclei. AB - The regulatory actions of estrogens on magnocellular oxytocin (OT) neurons of the paraventricular and supraoptic nuclei are well documented. Although the expression and distribution of nuclear estrogen receptor-beta, but not estrogen receptor-alpha, in the OT neuron has been described, the nuclear receptors may not explain all aspects of estrogen function in the hypothalamic OT neuron. Recently a G protein-coupled receptor (GPR) for estrogens, GPR30, has been identified as a membrane-localized estrogen receptor in several cancer cell lines. In this study, we therefore investigated the expression and localization of GPR30 in magnocellular OT neurons to understand the mode of rapid estrogen actions within these neurons. Here we show that, in the paraventricular nucleus and supraoptic nucleus, GPR30 is expressed in magnocellular OT neurons at both mRNA and protein levels but is not expressed in vasopressin neurons. Specific markers for intracellular organelles and immunoelectron microscopy revealed that GPR30 was localized mainly in the Golgi apparatus of the neurons but could not be detected at the cell surface. In addition, the expression of GPR30 is also detected in the neurohypophysis. These results suggest that GPR30 may serve primarily as a nongenomic transducer of estrogen actions in the hypothalamo neurohypophyseal system. PMID- 17872374 TI - Dioxin affects glucose transport via the arylhydrocarbon receptor signal cascade in pluripotent embryonic carcinoma cells. AB - Intoxication by dioxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads, among other damages, to early embryo loss, fetal malformations, and cardiovascular toxicity. Apart from binding to the arylhydrocarbon receptor (AhR), the mechanism of TCDD-mediated embryo toxicity is still unclear. We investigated possible modes of a TCDD-mediated toxicity, particularly in glucose metabolism, in pluripotent P19 mouse embryonic carcinoma cells. Undifferentiated P19 cells were exposed to 1-100 nM TCDD and characterized for AhR signaling. For studying cell differentiation, P19 cells were exposed to 10 nM TCDD at stage of embryoid body formation, and analyzed on glucose metabolism and cardiac differentiation during the next 3 wk. TCDD treatment activated the AhR-signaling cascade within 1 h, confirmed by AhR translocation, induction of cytochrome P450 1A1 expression, and activation of the xenobiotic response element. Although cell viability and transcription of the cardiac marker protein alpha-myosin heavy chain were affected, TCDD did not inhibit the differentiation of P19 cells to pulsating cardiomyocytes. TCDD significantly down-regulated the expression levels of the glucose transporter (GLUT) isoforms 1 and 3. After 24-h TCDD treatment, GLUT1 was no longer localized in the plasma membrane of P19 cells. The impaired GLUT expression correlated with a lower glucose uptake in 5-d-old embryoid bodies. The TCDD effects were mediated by AhR, as shown by preculture with the AhR antagonist alpha-naphthoflavone. Our data demonstrate that an AhR-mediated disturbance in GLUT expression and insufficient glucose uptake may be major mechanisms in TCDD embryo toxicity. PMID- 17872375 TI - Mechanism of the divergent effects of estrogen on the cell proliferation of human umbilical endothelial versus aortic smooth muscle cells. AB - Diverse estrogen actions are controlled via estrogen receptors (ERs). Mechanisms of action of ERs are modulated by various factors such as ER subtypes, conformation of the ER-ligand complex, and recruitment of coregulator complexes to a target gene promoter. Estrogen exerts divergent actions on vascular cells; namely it increases endothelial cell and inhibits smooth muscle cell growth, resulting in a vasoprotective action. We particularly focused on these divergent effects and examined the mechanisms. The effects of raloxifene, which shows estrogen-like vasoprotective actions, were also examined. To examine the effects of 17beta-estradiol (E(2)) and raloxifene on human aortic smooth muscle cells (HASMCs) and human umbilical venous endothelial cells (HUVECs), we evaluated the effect of E(2) and raloxifene on transcriptional activity, recruitment of the coregulator complex to a target gene promoter, and acetylation of histone of both the IGF-I and COX-2 genes. Treatment with E(2) or raloxifene increased both IGF-I and cyclooxygenase (COX)-2 mRNA expression in HUVECs, whereas they attenuated the serum-induced increase of these genes in HASMCs. Treatment by E(2) and raloxifene induced recruitment of coactivator complex and histone acetylation at both the IGF-I and COX-2 gene promoter in HUVECs. In contrast, in HASMCs, E(2), and raloxifene attenuated the serum-induced recruitment of coactivator complexes and histone acetylation at both the IGF-I and COX-2 gene promoters. Estrogen and raloxifene exert divergent transcriptional regulation on both mRNA expression and the remodeling of IGF-I and COX-2 gene promoters in HUVECs vs. HASMCs. PMID- 17872376 TI - Involvement of RelA-associated inhibitor in regulation of trophoblast differentiation via interaction with transcriptional factor specificity protein 1. AB - Glucose transporter-1 (GLUT1), one of the key functional indicators of placental differentiation, has an important role in placental glucose transport. We previously showed that the protein levels of GLUT1 and nuclear transcription factor specificity protein-1 (Sp1) in rat choriocarcinoma cells (Rcho-1 cells) decreased during the differentiation of these cells to giant cells. We also showed that Sp1 was involved in the regulation of GLUT1 gene expression during this process. RelA-associated inhibitor (RAI) is an inhibitor of nuclear factor kappaB that was identified by a yeast two-hybrid screen and is preferably expressed in human placenta and heart. RAI was also found to interact with Sp1 and exert an inhibitory effect against the DNA-binding activity of Sp1. We first show here that RAI mRNA expression increased as gestation proceeded and that RAI was localized mainly in the syncytiotrophoblast throughout pregnancy. The chloramphenicol acetyltransferase activity assay in Rcho-1 cells revealed that cotransfection of RAI expression vector resulted in decreased activity of the rat GLUT1 promoter but not in that of a mutated rat GLUT1 promoter lacking the Sp1 binding site. Furthermore, the protein level of RAI increased during differentiation. In addition, transfection of RAI expression vector promoted the morphological differentiation of Rcho-1 cells, and RAI knockdown using RAI specific small interfering RNA reveals inhibitory effects on the morphological differentiation, as assessed by photomicroscopy. Taken together, these findings suggest that RAI may be involved in the regulation of trophoblast differentiation via interaction with Sp1. PMID- 17872377 TI - Altered selectivity of parathyroid hormone (PTH) and PTH-related protein (PTHrP) for distinct conformations of the PTH/PTHrP receptor. AB - PTH and PTHrP use the same G protein-coupled receptor, the PTH/PTHrP receptor (PTHR), to mediate their distinct biological actions. The extent to which the mechanisms by which the two ligands bind to the PTHR differ is unclear. We examined this question using several pharmacological and biophysical approaches. Kinetic dissociation and equilibrium binding assays revealed that the binding of [(125)I]PTHrP(1-36) to the PTHR was more sensitive to GTPgammaS (added to functionally uncouple PTHR-G protein complexes) than was the binding of [(125)I]PTH(1-34) ( approximately 75% maximal inhibition vs. approximately 20%). Fluorescence resonance energy transfer-based kinetic analyses revealed that PTHrP(1-36) bound to the PTHR more slowly and dissociated from it more rapidly than did PTH(1-34). The cAMP signaling response capacity of PTHrP(1-36) in cells decayed more rapidly than did that of PTH(1-34) (t(1/2) = approximately 1 vs. approximately 2 h). Divergent residue 5 in the ligand, Ile in PTH and His in PTHrP, was identified as a key determinant of the altered receptor-interaction responses exhibited by the two peptides. We conclude that whereas PTH and PTHrP bind similarly to the G protein-coupled PTHR conformation (RG), PTH has a greater capacity to bind to the G protein-uncoupled conformation (R(0)) and, hence, can produce cumulatively greater signaling responses (via R(0)-->RG isomerization) than can PTHrP. Such conformational selectivity may relate to the distinct modes by which PTH and PTHrP act biologically, endocrine vs. paracrine, and may help explain reported differences in the effects that the ligands have on calcium and bone metabolism when administered to humans. PMID- 17872378 TI - 27-hydroxycholesterol is an endogenous selective estrogen receptor modulator. AB - Selective estrogen receptor (ER) modulators (SERMs) are ER ligands whose relative agonist/antagonist activities vary in a cell- and promoter-dependent manner. The molecular basis underlying this selectivity can be attributed to the ability of these ligands to induce distinct alterations in ER structure leading to differential recruitment of coactivators and corepressors. Whether SERM activity is restricted to synthetic ligands or whether molecules exist in vivo that function in an analogous manner remains unresolved. However, the recent observation that oxysterols bind ER and antagonize the actions of 17beta estradiol (E2) on the vascular wall suggests that this class of ligands may possess SERM activity. We demonstrate here that 27-hydroxycholesterol (27HC), the most prevalent oxysterol in circulation, functions as a SERM, the efficacy of which varies when assessed on different endpoints. Importantly, 27HC positively regulates both gene transcription and cell proliferation in cellular models of breast cancer. Using combinatorial peptide phage display, we have determined that 27HC induces a unique conformational change in both ERalpha and ERbeta, distinguishing it from E2 and other SERMs. Thus, as with other ER ligands, it appears that the unique pharmacological activity of 27HC relates to its ability to impact ER structure and modulate cofactor recruitment. Cumulatively, these data indicate that 27HC is an endogenous SERM with partial agonist activity in breast cancer cells and suggest that it may influence the pathology of breast cancer. Moreover, given the product-precursor relationship between 27HC and cholesterol, our findings have implications with respect to breast cancer risk in obese/hypercholesteremic individuals. PMID- 17872379 TI - Contributions of intracellular loops 2 and 3 of the lutropin receptor in Gs coupling. AB - A number of amino acids essential for Gs coupling, i.e. hot spots, were identified after in vitro Ala-scanning mutagenesis of the cytosolic extensions of helices 3, 5, and 6 and of intracellular loops 2 and 3 (IL2 and IL3) of the human LH receptor (LHR). Consistent with the results of in vitro experiments involving ligand binding and ligand-mediated signaling in transiently transfected human embryonic kidney 293 cells, computational modeling of the isolated receptor and of the receptor-G protein complexes suggests an important role of the cytosolic extension of helix 3 and the N-terminal portion of the IL2 in Gs(alpha) interaction, whereas the contribution of IL3 is marginal. Mapping the hot spots into the computational models of LHR and the LHR-Gs complexes allowed for a distinction between receptor sites required for intramolecular structural changes (i.e. I460, T461, H466, and I549) and receptor sites more likely involved in G protein recognition (i.e. R464, T467, I468, Y470, Y550, and D564). The latter sites include the highly conserved arginine of the (E/D)R(Y/W) motif, which is therefore likely to be a receptor recognition point for Gs rather than a switch of receptor activation. The results of in vitro and in silico experiments carried out in this study represent the first comprehensive delineation of functionality of the individual residues in the intracellular domains of LHR and establish potential switches of receptor activation as well as a map of the primary receptor recognition sites for Gs. A novel way to consider constitutively active mutants was inferred from this study, i.e. receptor states with improved complementarity for the G protein compared to the wild-type receptor. PMID- 17872380 TI - The thyroid hormone receptor-alpha (TRalpha) gene encoding TRalpha1 controls deoxyribonucleic acid damage-induced tissue repair. AB - The thyroid hormone (TH) controls, via its nuclear receptor, TH receptor-alpha1 (TRalpha1), intestinal crypt cell proliferation in the mouse. In order to understand whether this receptor also plays a role in intestinal regeneration after DNA damage, we applied a protocol of gamma-ray irradiation and monitored cell proliferation and apoptosis at several time points. In wild-type mice, the dose of 8 Gy induced cell cycle arrest and apoptosis in intestinal crypts a few hours after irradiation. This phenomenon reverted 48 h after irradiation. TRalpha(0/0) mutant mice displayed a constant low level of proliferating cells and a high apoptosis rate during the period of study. At the molecular level, in TRalpha(0/0) animals we observed a delay in the p53 phosphorylation induced by DNA damage. In our search for the expression of the protein kinases responsible for p53 phosphorylation upon irradiation, we have focused on DNA-dependent protein kinase catalytic subunit (DNA-PKcs). The number of cells expressing DNA PKcs in crypts remained high 48 h after irradiation, specifically in TRalpha mutants. Altogether, in TRalpha(0/0) animals the rate of apoptosis in crypt cells remained high, apparently due to an elevated number of cells still presenting DNA damage. In conclusion, the TRalpha gene plays a role in crypt cell homeostasis by regulating the rate of cell renewal and apoptosis induced by DNA damage. PMID- 17872381 TI - Preterm birth without progesterone withdrawal in 15-hydroxyprostaglandin dehydrogenase hypomorphic mice. AB - Parturition is a complex mammalian physiological process whose fundamental determinants have remained elusive. The increasing incidence of human preterm birth, a leading cause of infant mortality, highlights the importance of further understanding mechanisms regulating the timing of birth. Parturition is initiated in most nonprimate mammals, including mice, through a decrease in circulating progesterone caused by elevated prostaglandins. In humans, other higher primates, and guinea pigs, no consistent decrease in circulating progesterone occurs before the onset of labor. The divergence in endocrine control of labor initiation between most mammals compared with the great apes and guinea pigs gives rise to the question: how could a mechanism for the initiation of labor not requiring the withdrawal of progesterone evolve? Here, we genetically modulate prostaglandin signaling to determine the role of prostaglandin catabolism in the timing of birth. We find spontaneous preterm labor in the absence of progesterone withdrawal in 15-hydroxyprostaglandin dehydrogenase hypomorphic mice. The onset of labor in these hypomorphic mice is preceded by prematurely increased concentrations of prostaglandin E(2) and F(2alpha). Moreover, genetic crosses demonstrate a role for fetal genotype in birth timing. Together, these findings demonstrate a 15-hydroxyprostaglandin dehydrogenase-dependent shift in the physiology of murine parturition to one resembling the physiology of higher primates. Thus, endocrine control of labor has the capacity to plastically adapt to changes in genetically determined prostaglandin signals. PMID- 17872382 TI - OTX5 regulates pineal expression of the zebrafish REV-ERB alpha through a new DNA binding site. AB - The pineal gland plays a central role in the photoneuroendocrine system and acts as a photosensory organ in lower vertebrates. The orphan nuclear receptor Rev erbalpha (NR1D1) has previously been shown to be expressed in the pineal and to be regulated with a robust circadian rhythm during zebrafish embryogenesis. This early pineal expression is under the control of the transcription factor Orthodenticle homeobox 5 (Otx5). In this paper, we show that Otx5 regulates the second zfRev-erbalpha promoter, ZfP2. Despite the absence of a classical Otx binding site within ZfP2, this regulation depends on the integrity of the Otx5 homeodomain. Mapping experiments as well as EMSAs show that this interaction between Otx5 and ZfP2 depends on a noncanonical bipartite Otx-binding site (GANNCTTA and TAAA) that we called pineal expression related element (PERE). We showed that PERE is necessary for pineal expression in vivo by injecting zebrafish embryos with wild type and mutated versions of zfRev-erbalpha promoter fused to green fluorescent protein. Interestingly, PERE is found upstream of other genes expressed in the pineal gland, suggesting that it may play an important role in governing pineal expression. Our data establish that PERE is a novel cis-acting element contributing to pineal-specific gene expression and to Otx target gene regulation. PMID- 17872383 TI - Chronic fatigue syndrome is associated with chronic enterovirus infection of the stomach. AB - BACKGROUND AND AIMS: The aetiology for chronic fatigue syndrome (CFS) remains elusive although enteroviruses have been implicated as one of the causes by a number of studies. Since most CFS patients have persistent or intermittent gastrointestinal (GI) symptoms, the presence of viral capsid protein 1 (VP1), enterovirus (EV) RNA and culturable virus in the stomach biopsy specimens of patients with CFS was evaluated. METHODS: 165 consecutive patients with CFS underwent upper GI endoscopies and antrum biopsies. Immunoperoxidase staining was performed using EV-specific monoclonal antibody (mAb) or a control mAb specific for cytomegalovirus (CMV). RT-PCR ELISA was performed on RNA extracted from paraffin sections or samples preserved in RNA later. Biopsies from normal stomach and other gastric diseases served as controls. 75 samples were cultured for EV. RESULTS: 135/165 (82%) biopsies stained positive for VP1 within parietal cells, whereas 7/34 (20%) of the controls stained positive (p< or =0.001). CMV mAb failed to stain any of the biopsy specimens. Biopsies taken from six patients at the onset of the CFS/abdominal symptoms, and 2-8 years later showed positive staining in the paired specimens. EV RNA was detected in 9/24 (37%) paraffin embedded biopsy samples; 1/21 controls had detectable EV RNA (p<0.01); 1/3 patients had detectable EV RNA from two samples taken 4 years apart; 5 patient samples showed transient growth of non-cytopathic enteroviruses. CONCLUSION: Enterovirus VP1, RNA and non-cytopathic viruses were detected in the stomach biopsy specimens of CFS patients with chronic abdominal complaints. A significant subset of CFS patients may have a chronic, disseminated, non-cytolytic form of enteroviral infection, which could be diagnosed by stomach biopsy. PMID- 17872384 TI - Genetics of hypercalciuric nephrolithiasis: renal stone disease. AB - Renal stone disease (nephrolithiasis) affects 5% of adults and is often associated with hypercalciuria. Hypercalciuric nephrolithiasis is a familial disorder in more than 35% of patients, and may occur as a monogenic disorder, or as a polygenic trait involving 3 to 5 susceptibility loci in man and rat, respectively. Studies of monogenic forms of hypercalciuric nephrolithiasis in man, for example, Bartter syndrome, Dent's disease, autosomal dominant hypocalcemic hypercalciuria (ADHH), hypercalciuric nephrolithiasis with hypophosphatemia, and familial hypomagnesemia with hypercalciuria have helped to identify a number of transporters, channels, and receptors that are involved in regulating the renal tubular reabsorption of calcium. Thus, Bartter syndrome, an autosomal recessive disease, is caused by mutations of the bumetanide-sensitive Na-K-Cl (NKCC2) cotransporter, the renal outer-medullary potassium channel (ROMK), the voltage-gated chloride channel, CLC-Kb, or in its beta subunit, Barttin. Dent's disease, an X-linked disorder characterized by low molecular weight proteinuria, hypercalciuria, and nephrolithiasis, is due to mutations of the chloride/proton antiporter, CLC-5; ADHH is associated with activating mutations of the calcium-sensing receptor, which is a G protein-coupled receptor; hypophosphatemic hypercalciuric nephrolithiasis associated with rickets is due to mutations in the type 2c sodium-phosphate cotransporter (NPT2c); and familial hypomagnesemia with hypercalciuria is due to mutations of paracellin-1, which is a member of the claudin family of membrane proteins that form the intercellular tight junction barrier in a variety of epithelia. These studies have provided valuable insights into the renal tubular pathways that regulate calcium reabsorption and predispose to kidney stones and bone disease. PMID- 17872385 TI - Quantitative ultrasound technology in evaluating bone status and osteoporosis in patients with Cushing's syndrome. AB - Osteoporosis is a major feature of Cushing's syndrome (CS), and fragility fractures may be the first sign of the disease. The aim of this study was to evaluate the ability of quantitative ultrasound technology (QUS) in diagnosing osteoporosis in patients with CS. Sixty-three consecutive patients (mean age 38.6 +/- 13.0 years), 13 (20.6%) men and 50 (79.4%) women, with confirmed CS underwent both dual-energy X-ray densitometry (DXA) and QUS. Two groups of patients were selected: group A, 23 patients, T-score -2 SD or less (bone mineral density [BMD] femoral neck < or = 695 g/cm(2)), and group B, 40 patients, T-score above -2 SD. Age (42 +/- 12 vs. 37 +/- 13 years) and 24-h free urinary cortisol (499 +/- 345 vs. 469 +/- 319 microg/day) did not differ significantly (P = NS) between groups, while the body mass index did (24.3 +/- 4.1 vs. 28.1 +/- 4.6, P = 0.002). Unlike DXA, QUS values did not differ significantly (P = NS) between groups. Moreover, in the overall population, as well as in a single group, there was no correlation (R < 0.5, P = NS) between QUS and DXA parameters. In conclusion, in our study QUS was not able to differentiate osteoporotic patients from those with normal BMD measured by DXA, and thus QUS technology should not be used to discriminate between osteopenic and nonosteopenic patients with CS. PMID- 17872386 TI - Lights, camembert, action! The role of human orbitofrontal cortex in encoding stimuli, rewards, and choices. AB - This review outlines some of the main conclusions about the contributions of the orbitofrontal cortex to reward learning and decision making arising from functional neuroimaging studies in humans. It will be argued that human orbitofrontal cortex is involved in a number of distinct functions: signaling the affective value of stimuli as they are perceived, encoding expectations of future reward, and updating these expectations, either by making use of prediction error signals generated in the midbrain, or by using knowledge of the rules or structure of the decision problem. It will also be suggested that this region contributes to the decision making process itself, by encoding signals that inform an individual about what action to take next. Evidence for functional specialization within orbitofrontal cortex in terms of valence will also be evaluated, and the possible contributions of the orbitofrontal cortex in representing the values of actions as well as that of stimuli will be discussed. Finally, some of the outstanding questions for future neuroimaging research of orbitofrontal cortex function will be highlighted. PMID- 17872387 TI - The role of the orbitofrontal cortex in sensory-specific encoding of associations in pavlovian and instrumental conditioning. AB - A wide variety of associative learning tasks have been employed to assess the functional role of the orbitofrontal cortex (OFC) and related structures in learning. Many of these tasks were designed to assess the learning of highly specific associations between Pavlovian conditioned stimuli (or instrumental responses) and the sensory properties of reinforcement (i.e., sensory-specific associations). Current research suggests that OFC lesions impair behavioral control by these sensory-specific associations in unconditioned stimulus (US) devaluation, differential outcome, and Pavlovian-to-instrumental transfer experiments. In addition, although the OFC has been shown to be important in conditioned reinforcement but not in potentiated feeding tasks, versions of these tasks that assess control by sensory-specific associations have either not been run or they have not examined the effects of OFC lesions. Thus, firm conclusions from conditioned reinforcement and potentiated feeding studies cannot yet be drawn. Furthermore, studies examining the OFC's involvement in reversal learning have also suggested that associations between stimuli and reinforcement importantly depend upon a functioning OFC, possibly because this structure is needed to generate outcome expectancies useful in the computation of prediction errors ultimately used to "update" associations elsewhere (e.g., basolateral amygdala). Other work has shown that both original and reversed sensory-specific associations can control performance after different time delays following reversal learning. This suggests that structures outside of the OFC may be involved in the storage of originally acquired associations. Overall, this review makes clear that the OFC plays an important role in the encoding of sensory specific associations in a wide variety of learning tasks. PMID- 17872388 TI - Interactions between the orbitofrontal cortex and the hippocampal memory system during the storage of long-term memory. AB - It has been proposed that long-term declarative memories are ultimately stored through interactions between the hippocampal memory system and the neocortical association areas that initially processed the to-be-stored information. One association neocortex, the orbitofrontal cortex (OFC) is strongly and reciprocally connected with the hippocampal memory system and plays an important role in odor recognition memory in rats. We will report data from two studies: one that examined the firing of neurons in a task dependent on the parahippocampal region (PHR; including the perirhinal, postrhinal, and entrorhinal cortices), and one examined the firing of OFC neurons performing a task that is presumably dependent on the hippocampus. In the first study, we examined the role of OFC neurons in the continuous odor-guided nonmatching to sample task. While the firing of neurons in the PHR and OFC are similar in this task, there are several notable differences that are consistent with the idea that OFC is a high-order association cortex which interacts extensively with the PHR to store declarative memories. In the second study, we characterized the firing patterns of neurons in the OFC rats performing a passive, 8-odor-sequence memory task. Most interesting were neurons that fired selectively in anticipation of specific odors. We found that hippocampal lesions abolished the anticipatory firing in OFC, suggesting that these anticipatory responses (memory) were in fact dependent on the hippocampus, further supporting the view that the OFC interacts with the hippocampal memory system to store long-term, declarative memories. PMID- 17872389 TI - Neural encoding in the orbitofrontal cortex related to goal-directed behavior. AB - Research using laboratory animals, alongside clinical studies of human patients, support a role for the orbitofrontal cortex (OFC) in adaptive decision-making and goal-directed behavior. The functions of OFC neurons within this domain have been studied extensively in both rats and primates. Electrophysiological recordings during performance of relevant behavioral tasks provide a coherent portrait of OFC encoding that is reward related. OFC neurons represent associative relationships between events, encoding information that is predictive of outcome value. That encoding can be understood as a neural basis for deficits seen after OFC damage in the use of outcome expectancy to guide performance. There is less agreement, however, on whether OFC itself plays a role in translating information on outcome expectancy into the actual guidance of overt behavioral responding. New findings indicate that rat OFC neurons prominently encode additional task related information and events related to goal-directed action. This encoding can occur in populations of OFC neurons that are independent of the OFC neurons representing reward value. The significance of this emerging evidence may require studies that address the larger scale network through which OFC integrates expected outcome information with behavioral control. PMID- 17872390 TI - Cellular and molecular consequences of calcineurin A alpha gene deletion. AB - Here we briefly review our studies that have unraveled an important role for the calcium- and calmodulin-sensitive enzyme calcineurin (CN) in bone remodeling. We find that the genetic deletion of the calcineurin Aalpha isoform results in osteoporosis, which is recapitulated in humans following calcineurin inhibitor therapy widely used after solid organ transplantation. Mechanistically, however, while both calcineurin inhibitors cyclosporine and tacrolimus initially stimulate osteoclastic bone resorption in humans, the predominant feature in the CNAalpha null mouse is a profound reduction in bone formation. We speculate that the so called "calcineurin inhibitors" may interact with molecules other than calcineurin. The clinical relevance of these observations is explored. PMID- 17872391 TI - B lymphocytes and the skeleton. AB - Mesenchymal lineage cells arise from pluripotent stem cells in the bone marrow (BM) and transition through a series of developmental stages resulting in mature functional cells. This specification results in the development of osteoblast, adipocytes, myoblasts, chondroblasts, and stromal cells (part of the recticular network). The osteoblast developmental pathway is well understood particularly at the later stages of development. However, less is known about the very early stages, where cell fate decisions that lead to commitment to the osteoblast lineage occur. Adipocytes, the cells that produce fat, likely share a common early progenitor with osteoblasts, although little is known about the molecular control of this lineage bifurcation. Growing evidence indicates that transcription factors required for B lymphocyte development from hematopoietic stem cells are critical for proper skeletal development although as yet none have been implicated in osteoblast differentiation. We have discovered that O/E-1, a transcription factor essential for B cell development, is expressed in osteoblasts and plays a critical role in controlling osteoblast development. O/E 1-deficient mice are runted, have increased bone formation parameters, and have a striking increase in osteoblasts. Remarkably, these mice also exhibit a dramatic expansion of adipocytes in the medullary canal of long bones. PMID- 17872392 TI - The contribution of orbitofrontal cortex to action selection. AB - A number of recent findings suggest that the orbitofrontal cortex (OFC) influences action selection by providing information about the incentive value of behavioral goals or outcomes. However, much of this evidence has been derived from experiments using Pavlovian conditioning preparations of one form or another, making it difficult to determine whether the OFC is selectively involved in stimulus-outcome learning or whether it plays a more general role in processing reward value. Although many theorists have argued that these are fundamentally similar processes (i.e., that stimulus-reward learning provides the basis for choosing between actions based on anticipated reward value), several behavioral findings indicate that they are, in fact, dissociable. We have recently investigated the role of the OFC in the control of free operant lever pressing using tests that independently target the effect of stimulus-outcome learning and outcome devaluation on performance. We found that OFC lesions disrupted the tendency of Pavlovian cues to facilitate instrumental performance but left intact the suppressive effects of outcome devaluation. Rather than processing goal value, therefore, we hypothesize that the contribution of the OFC to goal-directed action is limited to encoding predictive stimulus-outcome relationships that can bias instrumental response selection. PMID- 17872393 TI - The orbitofrontal cortex: novelty, deviation from expectation, and memory. AB - The orbitofrontal cortex is strongly connected with limbic areas of the medial temporal lobe that are critically involved in the establishment of declarative memories (entorhinal and perirhinal cortex and the hippocampal region) as well as the amygdala and the hypothalamus that are involved in emotional and motivational states. The present article reviews evidence regarding the role of the orbitofrontal cortex in the processing of novel information, breaches of expectation, and memory. Functional neuroimaging evidence is provided that there is a difference between the anterior and posterior orbitofrontal cortex in such processing. Exposure to novel information gives rise to a selective increase of activity in the granular anterior part of the orbitofrontal cortex (area 11) and this activity increases when subjects attempt to encode this information in memory. If the stimuli violate expectations (e.g., inspection of graffiti-like stimuli in the context of other regular stimuli) or are unpleasant (i.e., exposure to the sounds of car crashes), there is increased response in the posteromedial agranular/dysgranular area 13 of the orbitofrontal region. The anatomic data provide a framework within which to understand these functional neuroimaging findings. PMID- 17872395 TI - Orbitofrontal cortex function and structure in depression. AB - The orbitofrontal cortex (OFC) has been implicated in the pathophysiology of major depression by evidence obtained using neuroimaging, neuropathologic, and lesion analysis techniques. The abnormalities revealed by these techniques show a regional specificity, and suggest that some OFC regions which appear cytoarchitectonically distinct also are functionally distinct with respect to mood regulation. For example, the severity of depression correlates inversely with physiological activity in parts of the posterior lateral and medial OFC, consistent with evidence that dysfunction of the OFC associated with cerebrovascular lesions increases the vulnerability for developing the major depressive syndrome. The posterior lateral and medial OFC function may also be impaired in individuals who develop primary mood disorders, as these patients show grey-matter volumetric reductions, histopathologic abnormalities, and altered hemodynamic responses to emotionally valenced stimuli, probabilistic reversal learning, and reward processing. In contrast, physiological activity in the anteromedial OFC situated in the ventromedial frontal polar cortex increases during the depressed versus the remitted phases of major depressive disorder to an extent that is positively correlated with the severity of depression. Effective antidepressant treatment is associated with a reduction in activity in this region. Taken together these data are compatible with evidence from studies in experimental animals indicating that some orbitofrontal and medial prefrontal cortex regions function to inhibit, while others function to enhance, emotional expression. Alterations in the functional balance between these regions and the circuits they form with anatomically related areas of the temporal lobe, striatum, thalamus, and brain stem thus may underlie the pathophysiology of mood disorders, such as major depression. PMID- 17872394 TI - The orbitofrontal cortex, real-world decision making, and normal aging. AB - The present series of three studies aims at investigating the hypothesis that some seemingly normal older persons have deficits in reasoning and decision making due to dysfunction in a neural system which includes the ventromedial prefrontal cortices. This hypothesis is relevant to the comprehensive study of aging, and also addresses the question of why so many older adults fall prey to fraud. To our knowledge, this work represents the first of its kind to begin to identify, from an individual-differences perspective, the behavioral, psychophysiological, and consumer correlates of defective decision making among healthy older adults. Our findings, in a cross-sectional sample of community dwelling participants, demonstrate that a sizeable subset of older adults (approximately 35-40%) perform disadvantageously on a laboratory measure of decision making that closely mimics everyday life, by the manner in which it factors in reward, punishment, risk, and ambiguity. These same poor decision makers display defective autonomic responses (or somatic markers), reminiscent of that previously established in patients with acquired prefrontal lesions. Finally, we present data demonstrating that poor decision makers are more likely to fall prey to deceptive advertising, suggesting compromise of real-world judgment and decision-making abilities. PMID- 17872396 TI - Morphogen receptor genes and metamorphogenes: skeleton keys to metamorphosis. AB - Morphogen receptors are nodal points in signal transduction pathways that regulate morphogenesis during embryonic development. A recent discovery identified a recurrent missense mutation in a gene encoding a morphogen receptor responsible for the elusive process of skeletal metamorphosis in humans. Metamorphosis, the postnatal transformation of one normal tissue or organ system into another, is a biological process rarely seen in higher vertebrates or mammals, but exemplified pathologically by the disabling autosomal dominant disorder, fibrodysplasia ossificans progressiva (FOP). Individuals with FOP experience episodes of spontaneous or trauma-induced metamorphosis that convert normal functioning aponeuroses, fascia, ligaments, tendons, and skeletal muscles into a highly ramified and disabling second skeleton of heterotopic bone. The recurrent single nucleotide missense mutation in the gene encoding activin receptor IA/activin-like kinase 2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor that causes FOP in all classically affected individuals worldwide, is one of the most specific disease-causing mutations in the human genome and the first identified human metamorphogene. These findings provide deep insight into a signaling pathway that regulates tissue and organ stability following morphogenesis, and that when dysregulated in a specific manner, orchestrates the metamorphosis of one normal tissue or organ system into another. The study of skeletal metamorphosis in FOP provides profound insight into the molecular mechanisms that ensure phenotypic stability following morphogenesis and that ordinarily lay deeply hidden in the highly conserved signaling pathways that regulate cell fate. Such insight is applicable to a broad range of human afflictions. PMID- 17872397 TI - Perspectives on olfactory processing, conscious perception, and orbitofrontal cortex. AB - The orbitofrontal cortex receives inputs from all the major sensory pathways, but olfaction is the only pathway that projects directly to it. We discuss several unique properties with which this is associated. Olfactory stimuli are converted into spatial images, varying in time, in the olfactory bulb, which are processed by the olfactory cortex for input to orbitofrontal cortex. The input from olfactory cortex to orbitofrontal cortex is mostly direct, though some fibers project through mediodorsal thalamus in some species. Studies are needed to determine the specific contributions of olfactory cortex and orbitofrontal cortex to conscious smell perception. A major challenge to the field is accounting for how conscious perception of this sense is coordinated with conscious perceptions of the other major senses, which are known to depend on thalamocortical circuits. The fact that the primary olfactory area at the neocortical level is embedded in the multisensory region of the orbitofrontal cortex indicates that at this level smell perception is heavily influenced by other senses, particularly related to food flavors through retronasal smell, which is being documented in experimental studies in rodents, nonhuman primates, and humans. Also requiring clarification is how behavioral modulation at each step of processing of the odor images is coordinated. In sum, the orbitofrontal cortex is emerging as the next frontier in understanding the neural basis of smell. PMID- 17872398 TI - A comparison of reward-contingent neuronal activity in monkey orbitofrontal cortex and ventral striatum: guiding actions toward rewards. AB - We have investigated how neuronal activity in the orbitofrontal-ventral striatal circuit is related to reward-directed behavior by comparing activity in these two regions during a visually guided reward schedule task. When a set of visual cues provides information about reward contingency, that is, about whether or not a trial will be rewarded, significant subpopulations of neurons in both orbitofrontal cortex and ventral striatum encode this information. Orbitofrontal and ventral striatal neurons also differentiate between rewarding and non rewarding trial outcomes, whether or not those outcomes were predicted. The size of the neuronal subpopulation encoding reward contingency is twice as large in orbitofrontal cortex (50% of neurons) as in ventral striatum (26%). Reward contingency-dependent activity also appears earlier during a trial in orbitofrontal cortex than in ventral striatum. The peak reward-contingency representation in orbitofrontal cortex (31% of neurons), occurs during the wait period, a period of high anticipation prior to any action. The peak ventral striatal representation of reward contingency (18%) occurs during the go period, a time of action. We speculate that signals from orbitofrontal cortex bias ventral striatal activity, and that a flow of reward-contingency information from orbitofrontal cortex to ventral striatum serves to guide actions toward rewards. PMID- 17872399 TI - Nuclear receptors and bone. AB - Nuclear receptors (NRs) represent a class of ligand-dependent and -independent transcription factors with importance to the regulation of development, reproduction, and metabolism. The emergence of new understanding of the structure, function, and role in disease of NRs provides new insights into the interaction between genetics and the environment, with NRs representing new targets for the development of therapeutic agents. NRs play key roles in bone health and contribute to our understanding of diseases and disorders that result in osteopenia and osteoporosis. The Nuclear Receptor Signaling Atlas (http://www.nursa.org) is an online repository of information about NRs and provides a community-wide resource designed to help catalyze new advances in biology and medicine. PMID- 17872400 TI - Flexible neural representations of value in the primate brain. AB - The amygdala and orbitofrontal cortex (OFC) are often thought of as components of a neural circuit that assigns affective significance--or value--to sensory stimuli so as to anticipate future events and adjust behavioral and physiological responses. Much recent work has been aimed at understanding the distinct contributions of the amygdala and OFC to these processes, but a detailed understanding of the physiological mechanisms underlying learning about value remains lacking. To gain insight into these processes, we have focused initially on characterizing the neural signals of the primate amygdala, and more recently of the primate OFC, during appetitive and aversive reinforcement learning procedures. We have employed a classical conditioning procedure whereby monkeys form associations between visual stimuli and rewards or aversive stimuli. After learning these initial associations, we reverse the stimulus-reinforcement contingencies, and monkeys learn these new associations. We have discovered that separate populations of neurons in the amygdala represent the positive and negative value of conditioned visual stimuli. This representation of value updates rapidly upon image value reversal, as fast as monkeys learn, often within a single trial. We suggest that representations of value in the amygdala may change through multiple interrelated mechanisms: some that arise from fairly simple Hebbian processes, and others that may involve gated inputs from other brain areas, such as the OFC. PMID- 17872401 TI - The effect of increased background resistance on the resistive load threshold for eliciting the respiratory-related evoked potential. AB - The detection threshold (DeltaR(50)) of resistive (R) loads is a function of the total background resistance (R(0)). Increased R(0) increases the DeltaR(50), but the ratio DeltaR(50)/R(0) remains constant. The respiratory-related evoked potential (RREP) is elicited only by R loads greater than the cognitive detection threshold, DeltaR(50). We hypothesized that the RREP Nf, P1, and N1 peaks will be elicited only when the added load DeltaR/R(0) is greater than the normal detection threshold, DeltaR(50)/R(0) = 0.30. We also hypothesized that when the R(0) is increased by adding extrinsic R, the RREP will not be elicited if the DeltaR/R(0) is less than the 0.30 ratio. RREPs were recorded with healthy volunteers (n = 20) respiring through a non-rebreathing valve. Three inspiratory R loads that spanned the DeltaR(50)/R(0) = 0.30 detection threshold were presented in two conditions: 1) no added R(0) (R1 < 0.30, R2 > 0.30, R3 > 0.30); and 2) increased R(0) = 13.3 cmH(2)O.l(-1).s (R1 < 0.30, R2 < 0.30, R3 > 0.30). For the control R(0), P1, Nf, and N1 peaks of the RREP were elicited by both R2 and R3, and not present with R1. The increased R(0) decreased R2/R(0) > 1.5 to R2/R(0) < 0.15. With increased R(0), the R1 and R2 loads did not elicit the RREP, but the Nf, P1, and N1 peaks were present for R3. These results demonstrate that the RREP is present if the DeltaR is above the cognitive detection threshold, and the RREP is absent if the load is below the detection threshold. When the R(0) is increased to make the DeltaR/R(0) less than the detection threshold, the DeltaR no longer elicits the RREP. PMID- 17872402 TI - Allergic lung inflammation affects central noradrenergic control of cholinergic outflow to the airways in ferrets. AB - Brain stem noradrenergic cell groups mediating autonomic responses to stress project to airway-related vagal preganglionic neurons (AVPNs). In ferrets, their activation produces withdrawal of cholinergic outflow to the airways via release of norepinephrine and activation of alpha(2A)-adrenergic receptors (alpha(2A)-AR) expressed by AVPNs. In these studies, we examined the effects of allergen exposure of the airway (AE) with ovalbumin on noradrenergic transmission regulating the activity of AVPNs and, consequently, airway smooth muscle tone. Experiments were performed in vehicle control (Con) and AE ferrets. Microperfusion of an alpha(2A)-AR agonist (guanabenz) in close proximity to AVPNs elicited more pronounced effects in Con than AE ferrets, including a decrease in unit activity and reflexly evoked responses of putative AVPN neurons with a corresponding decrease in cholinergic outflow to the airways. Although no differences were found in the extent of noradrenergic innervation of the AVPNs, RT-PCR and Western blot studies demonstrated that AE and repeated exposure to antigen significantly reduced expression of alpha(2A)-ARs at message and protein levels. These findings indicate that, in an animal model of allergic asthma, sensitization and repeated challenges with a specific allergen diminish central inhibitory noradrenergic modulation of AVPNs, possibly via downregulation of alpha(2A)-AR expression by these neurons. PMID- 17872403 TI - Hypergravity resistance exercise: the use of artificial gravity as potential countermeasure to microgravity. AB - The aims of this study were to 1) determine if hypergravity (HG) squats can produce foot forces similar to those measured during 10-repetition maximum (10RM) squats using weights under normal 1-G(z) condition, and 2) compare the kinematics (duration and goniometry) and EMG activities of selected joints and muscles between 10RM and HG squats of similar total foot forces. Eight men and six women [27 yr (SD 4), 66 kg (SD 10)] completed ten 10RM [83 kg (SD 23)] and 10 HG squats (2.25-3.75 G(z)). HG squats were performed on a human-powered short-arm centrifuge. Foot forces were measured using insole force sensors. Hip, knee, and ankle angles were measured using electrogoniometers. EMG activities of the erector spinae, biceps femoris, rectus femoris, and gastrocnemius were also recorded during both squats. All subjects were able to achieve similar or higher average total foot forces during HG squats compared with those obtained during 10RM squats. There were no differences in total duration per set, average duration per repetition, and goniometry and EMG activities of the selected joints and muscles, respectively, between 10RM and HG squats. These results demonstrate that HG squats can produce very high foot forces that are comparable to those produced during 10RM squats at 1 G(z). In addition, the technique and muscle activation are similar between the two types of squats. This observation supports the view that HG resistance training may represent an important countermeasure to microgravity. PMID- 17872404 TI - End-expiratory and tidal volumes measured in conscious mice using single projection x-ray images. AB - The evaluation of airway resistance (R(aw)) in conscious mice requires both end expiratory (V(e)) and tidal volumes (V(t)) (Lai-Fook SJ and Lai YL. J Appl Physiol 98: 2204-2218, 2005). In anesthetized BALB/c mice we measured lung area (A(L)) from ventral-to-dorsal x-ray images taken at FRC (V(e)) and after air inflation with 0.25 and 0.50 ml (DeltaV(L)). Total lung volume (V(L)) described by equation: V(L) = DeltaV(L) + V(FRC) = KA(L)(1.5) assumed uniform (isotropic) inflation. Total V(FRC) averaged 0.55 ml, consisting of 0.10 ml tissue, 0.21 ml blood and 0.24 ml air. K averaged 1.84. In conscious mice in a sealed box, we measured the peak-to-peak box pressure excursions (DeltaP(b)) and x-rays during several cycles. K was used to convert measured A(L)(1.5) to V(L) values. We calculated V(e) and V(t) from the plot of V(L) vs. cos(alpha - phi). Phase angle alpha was the minimum point of the P(b) cycle to the x-ray exposure. Phase difference between the P(b) and V(L) cycles (phi) was measured from DeltaP(b) values using both room- and body-temperature humidified box air. A similar analysis was used after aerosol exposures to bronchoconstrictor methacholine (Mch), except that phi depended also on increased R(aw). In conscious mice, V(e) (0.24 ml) doubled after Mch (50-125 mg/ml) aerosol exposure with constant V(t), frequency (f), DeltaP(b), and R(aw). In anesthetized mice, in addition to an increased V(e), repeated 100 mg/ml Mch exposures increased both DeltaP(b) and R(aw) and decreased f to apnea in 10 min. Thus conscious mice adapted to Mch by limiting R(aw), while anesthesia resulted in airway closure followed by diaphragm fatigue and failure. PMID- 17872405 TI - Combined isometric, concentric, and eccentric resistance exercise prevents unloading-induced muscle atrophy in rats. AB - Previously, we reported that an isometric resistance training program that was effective in stimulating muscle hypertrophy in ambulatory rats could not completely prevent muscle atrophy during unloading (Haddad F, Adams GR, Bodell PW, Baldwin KM. J Appl Physiol 100: 433-441, 2006). These results indicated that preventing muscle atrophy does not appear to be simply a function of providing an anabolic stimulus. The present study was undertaken to determine if resistance training, with increased volume (3-s contractions) and incorporating both static and dynamic components, would be effective in preventing unloading-induced muscle atrophy. Rats were exposed to 5 days of muscle unloading via tail suspension. During that time one leg received electrically stimulated resistance exercise (RE) that included an isometric, concentric, and eccentric phase. The results of this study indicate that this combined-mode RE provided an anabolic stimulus sufficient to maintain the mass and myofibril content of the trained but not the contralateral medial gastrocnemius (MG) muscle. Relative to the contralateral MG, the RE stimulus increased the amount of total RNA (indicative of translational capacity) as well as the mRNA for several anabolic/myogenic markers such as insulin-like growth factor-I, myogenin, myoferlin, and procollagen III-alpha-1 and decreased that of myostatin, a negative regulator of muscle size. The combined-mode RE protocol also increased the activity of anabolic signaling intermediates such as p70S6 kinase. These results indicate that a combination of static- and dynamic-mode RE of sufficient volume provides an effective stimulus to stimulate anabolic/myogenic mechanisms to counter the initial stages of unloading-induced muscle atrophy. PMID- 17872406 TI - Combined aerobic and resistance training and vascular function: effect of aerobic exercise before and after resistance training. AB - Aerobic exercise training combined with resistance training (RT) might prevent the deterioration of vascular function. However, how aerobic exercise performed before or after a bout of RT affects vascular function is unknown. The present study investigates the effect of aerobic exercise before and after RT on vascular function. Thirty-three young, healthy subjects were randomly assigned to groups that ran before RT (BRT: 4 male, 7 female), ran after RT (ART: 4 male, 7 female), or remained sedentary (SED: 3 male, 8 female). The BRT and ART groups performed RT at 80% of one repetition maximum and ran at 60% of the targeted heart rate twice each week for 8 wk. Both brachial-ankle pulse wave velocity (baPWV) and flow-mediated dilation (FMD) after combined training in the BRT group did not change from baseline. In contrast, baPWV after combined training in the ART group reduced from baseline (from 1,025 +/- 43 to 910 +/- 33 cm/s, P < 0.01). Moreover, brachial artery FMD after combined training in the ART group increased from baseline (from 7.3 +/- 0.8 to 9.6 +/- 0.8%, P < 0.01). Brachial artery diameter, mean blood velocity, and blood flow in the BRT and ART groups after combined training increased from baseline (P < 0.05, P < 0.01, and P < 0.001, respectively). These values returned to the baseline during the detraining period. These values did not change in the SED group. These results suggest that although vascular function is not improved by aerobic exercise before RT, performing aerobic exercise thereafter can prevent the deteriorating of vascular function. PMID- 17872407 TI - Hypoxia has a greater effect than exercise on the redistribution of pulmonary blood flow in swine. AB - Strenuous exercise combined with hypoxia is implicated in the development of high altitude pulmonary edema (HAPE), which is believed to result from rupture of pulmonary capillaries secondary to high vascular pressures. The relative importance of hypoxia and exercise in altering the distribution of pulmonary blood flow (PBF) is unknown. Six chronically catheterized specific pathogen-free Yorkshire hybrid pigs (25.5 +/- 0.7 kg, means +/- SD) underwent incremental treadmill exercise tests in normoxia (Fi(O(2)) = 0.21) and hypoxia (Fi(O(2)) = 0.125, balanced order), consisting of 5 min at 30, 60, and 90% of the previously determined Vo(2max). At steady state (~4 min), metabolic and cardiac output data were collected and fluorescent microspheres were injected over approximately 30 s. Later the fluorescent intensity of each color in each 2-cm(3) lung piece was determined and regional perfusion was calculated from the weight-normalized fluorescence. Both hypoxia and exercise shifted PBF away from the ventral cranial lung regions toward the dorsal caudal regions of the lung, but hypoxia caused a greater dorsal caudal shift in PBF at rest than did near-maximal exercise in normoxia. The variance in PBF due to hypoxia, exercise, and vascular structure was 16 +/- 4.2, 4.0 +/- 4.4, and 59.4 +/- 11.4%, respectively, and the interaction between hypoxia and exercise represented 12 +/- 6.5%. This observation implies that there is already a maximal shift with in PBF with hypoxia in the dorsal-caudal regions in pigs that cannot be exceeded with the addition of exercise. However, exercise greatly increases the pulmonary arterial pressures and therefore the risk of capillary rupture in high flow regions. PMID- 17872408 TI - Altered hormonal regulation and blood flow distribution with cardiovascular deconditioning after short-duration head down bed rest. AB - This study tested the hypothesis that cardiovascular and hormonal responses to lower body negative pressure (LBNP) would be altered by 4-h head down bed rest (HDBR) in 11 healthy young men. In post-HDBR testing, three subjects failed to finish the protocol due to presyncopal symptoms, heart rate was increased during LBNP compared with pre-HDBR, mean arterial blood pressure was elevated at 0, -10, and -20 mmHg and reduced at -40 mmHg, central venous pressure (CVP) and cardiac stroke volume were reduced at all levels of LBNP. Plasma concentrations of renin, angiotensin II, and aldosterone were significantly lower after HDBR. Renin and angiotensin II increased in response to LBNP only post-HDBR. There was no effect of HDBR or LBNP on norepinephrine while epinephrine tended to increase at -40 mmHg post-HDBR (P = 0.07). Total blood volume was not significantly reduced. Splanchnic blood flow taken from ultrasound measurement of the portal vein was higher at each level of LBNP post-compared with pre-HDBR. The gain of the cardiopulmonary baroreflex relating changes in total peripheral resistance to CVP was increased after HDBR, but splanchnic vascular resistance was actually reduced. These results are consistent with our hypothesis and suggest that cardiovascular instability following only 4-h HDBR might be related to altered hormonal and/or neural control of regional vascular resistance. Impaired ability to distribute blood away from the splanchnic region was associated with reduced stroke volume, elevated heart rate, and the inability to protect mean arterial pressure. PMID- 17872409 TI - Mass-dependent and -independent fractionation of hg isotopes by photoreduction in aquatic systems. AB - Mercury (Hg) isotopes can be used as tracers of Hg biogeochemical pathways in the environment. The photochemical reduction of aqueous Hg species by natural sunlight leads to both mass-dependent fractionation (MDF) of Hg isotopes and mass independent fractionation (MIF) of the odd-mass isotopes, with the relation between the MIF for the two odd isotopes being distinct for different photoreduction pathways. Large variations in MDF and MIF are observed in fish and provide new insights into the sources and bioaccumulation of Hg in food webs. MIF in fish can also be used to estimate the loss of methylmercury via photoreduction in aquatic ecosystems. PMID- 17872410 TI - FKF1 and GIGANTEA complex formation is required for day-length measurement in Arabidopsis. AB - Precise timing of CONSTANS (CO) gene expression is necessary for day-length discrimination for photoperiodic flowering. The FLAVIN-BINDING, KELCH REPEAT, F BOX 1 (FKF1), and GIGANTEA (GI) proteins regulate CO transcription in Arabidopsis. We demonstrate that FKF1 and GI proteins form a complex in a blue light-dependent manner. The timing of this interaction regulates the timing of daytime CO expression. FKF1 function is dependent on GI, which interacts with a CO repressor, CYCLING DOF FACTOR 1 (CDF1), and controls CDF1 stability. GI, FKF1, and CDF1 proteins associate with CO chromatin. Thus, the FKF1-GI complex forms on the CO promoter in late afternoon to regulate CO expression, providing a mechanistic view of how the coincidence of light with circadian timing regulates photoperiodic flowering. PMID- 17872412 TI - An icy partnership. PMID- 17872413 TI - Space physics. Beyond Einstein should start with dark energy probe, says panel. PMID- 17872411 TI - Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies. AB - Targeted therapies that inhibit receptor tyrosine kinases (RTKs) and the downstream phosphatidylinositol 3-kinase (PI3K) signaling pathway have shown promising anticancer activity, but their efficacy in the brain tumor glioblastoma multiforme (GBM) and other solid tumors has been modest. We hypothesized that multiple RTKs are coactivated in these tumors and that redundant inputs drive and maintain downstream signaling, thereby limiting the efficacy of therapies targeting single RTKs. Tumor cell lines, xenotransplants, and primary tumors indeed show multiple concomitantly activated RTKs. Combinations of RTK inhibitors and/or RNA interference, but not single agents, decreased signaling, cell survival, and anchorage-independent growth even in glioma cells deficient in PTEN, a frequently inactivated inhibitor of PI3K. Thus, effective GBM therapy may require combined regimens targeting multiple RTKs. PMID- 17872414 TI - U.S. national security. Scientists fear curbs on access to satellite data. PMID- 17872415 TI - Genomics. A little gene xeroxing goes a long way. PMID- 17872416 TI - Conservation. Scientists say Ebola has pushed western gorillas to the brink. PMID- 17872417 TI - Epidemiology. Tropical disease follows mosquitoes to Europe. PMID- 17872419 TI - Biodefense research. Lapses in biosafety spark concern. PMID- 17872418 TI - Biosecurity. Reports blame animal health lab in foot-and-mouth whodunit. PMID- 17872420 TI - Psychiatric research. Is internal timing key to mental health? PMID- 17872421 TI - Ecology. Can palm oil plantations come clean? PMID- 17872422 TI - Research in Japan. Big winners, big expectations. PMID- 17872424 TI - The gonzo scientist. A summer camp for grown-up geeks. PMID- 17872423 TI - Tropical diseases. Hunt for dengue vaccine heats up as the disease burden grows. PMID- 17872425 TI - Why do team-authored papers get cited more? PMID- 17872426 TI - Coral reefs still in danger from tourism head. PMID- 17872427 TI - Comment on "The consensus coding sequences of human breast and colorectal cancers". AB - Sjoblom et al. (Research Articles, 13 October 2006, p. 268) used data from cancer genome resequencing to identify genes with elevated mutation rates. Their analysis used point probabilities when it should have used P values for the hypotheses they intended to test. Reimplementing their analysis method with exact P values results in far fewer genes with mutation rates that achieve statistical significance. PMID- 17872428 TI - Comment on "The consensus coding sequences of human breast and colorectal cancers". AB - Sjoblom et al. (Research Article, 13 October 2006, p. 268) reported nearly 200 novel cancer genes said to have a 90% probability of being involved in colon or breast cancer. However, their analysis raises two statistical concerns. When these concerns are addressed, few genes with significantly elevated mutation rates remain. Although the biological methodology in Sjoblom et al. is sound, more samples are needed to achieve sufficient power. PMID- 17872429 TI - Comment on "The consensus coding sequences of human breast and colorectal cancers". AB - Sjoblom et al. (Research Article, 13 October 2006, p. 268) reported many new genes with an apparent significant excess of mutations in breast and colorectal cancer. Reanalysis of their data with more appropriate statistical methods and background mutation rate assumptions reveals that few if any of these genes have significantly elevated mutation rates. PMID- 17872430 TI - Climate change. The limits of consensus. PMID- 17872431 TI - Immunology. Square-dancing antibodies. PMID- 17872432 TI - Geochemistry. New players in an ancient cycle. PMID- 17872433 TI - Computer science. Cultural modeling in real time. PMID- 17872434 TI - Microbiology. Sizing up the uncultivated majority. PMID- 17872435 TI - Astronomy. From darkness to light. PMID- 17872436 TI - Complexity of coupled human and natural systems. AB - Integrated studies of coupled human and natural systems reveal new and complex patterns and processes not evident when studied by social or natural scientists separately. Synthesis of six case studies from around the world shows that couplings between human and natural systems vary across space, time, and organizational units. They also exhibit nonlinear dynamics with thresholds, reciprocal feedback loops, time lags, resilience, heterogeneity, and surprises. Furthermore, past couplings have legacy effects on present conditions and future possibilities. PMID- 17872437 TI - Production of trout offspring from triploid salmon parents. AB - Many salmonids have become at risk of extinction. For teleosts whose eggs cannot be cryopreserved, developing techniques other than egg cryopreservation to save genetic resources is imperative. In this study, spermatogonia from rainbow trout were intraperitoneally transplanted into newly hatched sterile triploid masu salmon. Transplanted trout spermatogonia underwent spermatogenesis and oogenesis in male and female recipients, respectively. At 2 years after transplantation, triploid salmon recipients only produced trout sperm and eggs. With use of these salmon as parents, we successfully produced only donor-derived trout offspring. Thus, by transplanting cryopreserved spermatogonia into sterile xenogeneic recipients, we can generate individuals of a threatened species. PMID- 17872438 TI - TLR3 deficiency in patients with herpes simplex encephalitis. AB - Some Toll and Toll-like receptors (TLRs) provide immunity to experimental infections in animal models, but their contribution to host defense in natural ecosystems is unknown. We report a dominant-negative TLR3 allele in otherwise healthy children with herpes simplex virus 1 (HSV-1) encephalitis. TLR3 is expressed in the central nervous system (CNS), where it is required to control HSV-1, which spreads from the epithelium to the CNS via cranial nerves. TLR3 is also expressed in epithelial and dendritic cells, which apparently use TLR3 independent pathways to prevent further dissemination of HSV-1 and to provide resistance to other pathogens in TLR3-deficient patients. Human TLR3 appears to be redundant in host defense to most microbes but is vital for natural immunity to HSV-1 in the CNS, which suggests that neurotropic viruses have contributed to the evolutionary maintenance of TLR3. PMID- 17872439 TI - Lighting the universe with filaments. AB - The first stars in the universe form when chemically pristine gas heats as it falls into dark-matter potential wells, cools radiatively because of the formation of molecular hydrogen, and becomes self-gravitating. Using supercomputer simulations, we demonstrated that the stars' properties depend critically on the currently unknown nature of the dark matter. If the dark-matter particles have intrinsic velocities that wipe out small-scale structure, then the first stars form in filaments with lengths on the order of the free-streaming scale, which can be approximately 10(20) meters (approximately 3 kiloparsecs, corresponding to a baryonic mass of approximately 10(7) solar masses) for realistic "warm dark matter" candidates. Fragmentation of the filaments forms stars with a range of masses, which may explain the observed peculiar element abundance pattern of extremely metal-poor stars, whereas coalescence of fragments and stars during the filament's ultimate collapse may seed the supermassive black holes that lurk in the centers of most massive galaxies. PMID- 17872440 TI - Phase-coherent transport in graphene quantum billiards. AB - As an emergent electronic material and model system for condensed-matter physics, graphene and its electrical transport properties have become a subject of intense focus. By performing low-temperature transport spectroscopy on single-layer and bilayer graphene, we observe ballistic propagation and quantum interference of multiply reflected waves of charges from normal electrodes and multiple Andreev reflections from superconducting electrodes, thereby realizing quantum billiards in which scattering only occurs at the boundaries. In contrast to the conductivity of conventional two-dimensional materials, graphene's conductivity at the Dirac point is geometry-dependent because of conduction via evanescent modes, approaching the theoretical value 4e(2)/pih (where e is the electron charge and h is Planck's constant) only for short and wide devices. These distinctive transport properties have important implications for understanding chaotic quantum systems and implementing nanoelectronic devices, such as ballistic transistors. PMID- 17872441 TI - Early Archaean microorganisms preferred elemental sulfur, not sulfate. AB - Microscopic sulfides with low 34S/32S ratios in marine sulfate deposits from the 3490-million-year old Dresser Formation, Australia, have been interpreted as evidence for the presence of early sulfate-reducing organisms on Earth. We show that these microscopic sulfides have a mass-independently fractionated sulfur isotopic anomaly (Delta33S) that differs from that of their host sulfate (barite). These microscopic sulfides could not have been produced by sulfate reducing microbes, nor by abiologic processes that involve reduction of sulfate. Instead, we interpret the combined negative delta34S and positive Delta33S signature of these microscopic sulfides as evidence for the early existence of organisms that disproportionate elemental sulfur. PMID- 17872442 TI - Current-induced magnetization switching with a spin-polarized scanning tunneling microscope. AB - Switching the magnetization of a magnetic bit by injection of a spin-polarized current offers the possibility for the development of innovative high-density data storage technologies. We show how individual superparamagnetic iron nanoislands with typical sizes of 100 atoms can be addressed and locally switched using a magnetic scanning probe tip, thus demonstrating current-induced magnetization reversal across a vacuum barrier combined with the ultimate resolution of spin-polarized scanning tunneling microscopy. Our technique allows us to separate and quantify three fundamental contributions involved in magnetization switching (i.e., current-induced spin torque, heating the island by the tunneling current, and Oersted field effects), thereby providing an improved understanding of the switching mechanism. PMID- 17872443 TI - Global pattern formation and ethnic/cultural violence. AB - We identify a process of global pattern formation that causes regions to differentiate by culture. Violence arises at boundaries between regions that are not sufficiently well defined. We model cultural differentiation as a separation of groups whose members prefer similar neighbors, with a characteristic group size at which violence occurs. Application of this model to the area of the former Yugoslavia and to India accurately predicts the locations of reported conflict. This model also points to imposed mixing or boundary clarification as mechanisms for promoting peace. PMID- 17872444 TI - Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defense. AB - Membrane attack is important for mammalian immune defense against invading microorganisms and infected host cells. Proteins of the complement membrane attack complex (MAC) and the protein perforin share a common MACPF domain that is responsible for membrane insertion and pore formation. We determined the crystal structure of the MACPF domain of complement component C8alpha at 2.5 angstrom resolution and show that it is structurally homologous to the bacterial, pore forming, cholesterol-dependent cytolysins. The structure displays two regions that (in the bacterial cytolysins) refold into transmembrane beta hairpins, forming the lining of a barrel pore. Local hydrophobicity explains why C8alpha is the first complement protein to insert into the membrane. The size of the MACPF domain is consistent with known C9 pore sizes. These data imply that these mammalian and bacterial cytolytic proteins share a common mechanism of membrane insertion. PMID- 17872445 TI - Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. AB - Antibodies play a central role in immunity by forming an interface with the innate immune system and, typically, mediate proinflammatory activity. We describe a novel posttranslational modification that leads to anti-inflammatory activity of antibodies of immunoglobulin G, isotype 4 (IgG4). IgG4 antibodies are dynamic molecules that exchange Fab arms by swapping a heavy chain and attached light chain (half-molecule) with a heavy-light chain pair from another molecule, which results in bispecific antibodies. Mutagenesis studies revealed that the third constant domain is critical for this activity. The impact of IgG4 Fab arm exchange was confirmed in vivo in a rhesus monkey model with experimental autoimmune myasthenia gravis. IgG4 Fab arm exchange is suggested to be an important biological mechanism that provides the basis for the anti-inflammatory activity attributed to IgG4 antibodies. PMID- 17872446 TI - Functional architecture and evolution of transcriptional elements that drive gene coexpression. AB - Transcriptional coexpression of interacting gene products is required for complex molecular processes; however, the function and evolution of cis-regulatory elements that orchestrate coexpression remain largely unexplored. We mutagenized 19 regulatory elements that drive coexpression of Ciona muscle genes and obtained quantitative estimates of the cis-regulatory activity of the 77 motifs that comprise these elements. We found that individual motif activity ranges broadly within and among elements, and among different instantiations of the same motif type. The activity of orthologous motifs is strongly constrained, although motif arrangement, type, and activity vary greatly among the elements of different co regulated genes. Thus, the syntactical rules governing this regulatory function are flexible but become highly constrained evolutionarily once they are established in a particular element. PMID- 17872447 TI - Mutual feedbacks maintain both genetic and species diversity in a plant community. AB - The forces that maintain genetic diversity among individuals and diversity among species are usually studied separately. Nevertheless, diversity at one of these levels may depend on the diversity at the other. We have combined observations of natural populations, quantitative genetics, and field experiments to show that genetic variation in the concentration of an allelopathic secondary compound in Brassica nigra is necessary for the coexistence of B. nigra and its competitor species. In addition, the diversity of competing species was required for the maintenance of genetic variation in the trait within B. nigra. Thus, conservation of species diversity may also necessitate maintenance of the processes that sustain the genetic diversity of each individual species. PMID- 17872448 TI - Quantitative imaging of nitrogen fixation by individual bacteria within animal cells. AB - Biological nitrogen fixation, the conversion of atmospheric nitrogen to ammonia for biosynthesis, is exclusively performed by a few bacteria and archaea. Despite the essential importance of biological nitrogen fixation, it has been impossible to quantify the incorporation of nitrogen by individual bacteria or to map the fate of fixed nitrogen in host cells. In this study, with multi-isotope imaging mass spectrometry we directly imaged and measured nitrogen fixation by individual bacteria within eukaryotic host cells and demonstrated that fixed nitrogen is used for host metabolism. This approach introduces a powerful way to study microbes and global nutrient cycles. PMID- 17872449 TI - 4-Hydroxy-2-nonenal increases superoxide anion radical in endothelial cells via stimulated GTP cyclohydrolase proteasomal degradation. AB - OBJECTIVE: 4-Hydroxy-2-nonenal (4-HNE) is an abundant electrophilic lipid that mediates oxidative stress in endothelium by mechanisms that remain controversial. This study examines the effects of 4-HNE on nitric oxide (NO) and superoxide levels in bovine aorta endothelial cells (BAECs). METHODS AND RESULTS: Exposure of BAECs to 4-HNE caused a dose-dependent inhibition of NO that correlated with losses of hsp90 and phosphorylated eNOS-serine1179 but not eNOS protein levels. 4 HNE failed to inhibit NO production in sepiapterin and ascorbate supplemented cells suggesting that tetrahydrobiopterin (BH4) is a limiting factor in non supplemented cells. This was verified by quantification of BH4 by high performance liquid chromatography analysis with electrochemical detection and by examining GTP cyclohydrolase I (GTPCH) protein levels and activity all of which were diminished by 4-HNE treatment. Analysis of 2-hydroxyethidium indicated that 4-HNE increased superoxide release in BAECs. The effects of 4-HNE on GTPCH and hsp90 were efficiently counteracted by proteasomal inhibition, indicating that depletion of BH4 by 4-HNE is attributable to specific mechanisms involving protein degradation. CONCLUSIONS: 4-HNE by altering BH4 homeostasis mediates eNOS uncoupling and superoxide generation in BAECs. By also decreasing phosphorylation of eNOS-serine 1179 4-HNE may specifically regulate NO/reactive oxygen species fluxes in the endothelium with important consequences to redox signaling. PMID- 17872450 TI - Multiple effects of high mobility group box protein 1 in skeletal muscle regeneration. AB - OBJECTIVE: High mobility group box 1 protein (HMGB1) is a cytokine released by necrotic and inflammatory cells in response to injury. We examined the role of HMGB1 in skeletal muscle regeneration after hindlimb ischemia. METHODS AND RESULTS: Unilateral hindlimb ischemia was induced in mice by femoral artery dissection. HMGB1 levels increased in regenerating skeletal muscle and the blockade of endogenous HMGB1 by the administration of its truncated form, the BoxA, resulted in the reduction of vessel density. In contrast, intramuscular administration of HMGB1 enhanced perfusion and increased the number of regenerating fibers. To separately study the myogenic and the angiogenic effects of HMGB1, in vitro experiments were performed with isolated myoblasts and endothelial cells. Myoblasts were found to express the HMGB1 receptor RAGE and TLR4 which were downregulated during in vitro myogenic differentiation. HMGB1 was extracellularly released by differentiated myoblasts and exerted a chemotactic activity on myogenic cells. This effect was partially dependent on RAGE and was inhibited by BoxA treatment. Finally, HMGB1 stimulated tubular-like structure formation by endothelial cells through the activation of extracellular signal regulated kinase (ERK) and JNK signal transduction pathways. CONCLUSIONS: HMGB1 plays a role in skeletal muscle regeneration modulating, in an autocrine paracrine manner, myoblast and endothelial cell functions. PMID- 17872451 TI - Nateglinide reduces carotid intima-media thickening in type 2 diabetic patients under good glycemic control. AB - OBJECTIVE: Postprandial hyperglycemia observed in type 2 diabetes mellitus is a risk factor for atherosclerosis. The aim of this study was to investigate the effect of strict glycemic control by nateglinide on common carotid far wall intima-media thickness in type 2 diabetic patients who were already under good glycemic control. METHODS AND RESULTS: We performed an open labeled randomized prospective trial on 78 drug-naive type 2 diabetic patients whose HbA1c was less than 6.5%. Thirty-eight patients were randomly assigned to receive nateglinide (270 mg/dL) and 40 to control group (no treatment). After 12 months, a significant reduction in HbA1c was observed in the nateglinide group, whereas a significant increase of HbA1c was observed in the untreated group. The carotid intima-media thickness at the end of 1-year follow-up was significantly reduced in the nateglinide group compared with the untreated group (-0.017+/-0.054 mm/year versus 0.024+/-0.066 mm/year, P=0.0064). Whereas nateglinide treatment also reduced triglyceride, highly-sensitive C-reactive protein, and E-selectin, multiple regression analysis identified HbA1c as the only significant independent determinant of the change in carotid intima-media thickness. CONCLUSION: In type 2 diabetic patients with good glycemic control, further strict glycemic control by nateglinide results in regression of carotid intima-media thickness. PMID- 17872452 TI - Epoxyeicosatrienoic acids regulate Trp channel dependent Ca2+ signaling and hyperpolarization in endothelial cells. AB - OBJECTIVE: An initial step in endothelium-derived hyperpolarizing factor-mediated responses is endothelial cell hyperpolarization. Here we address the mechanisms by which cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) contribute to this effect in native and cultured endothelial cells. METHODS AND RESULTS: In native CYP2C-expressing endothelial cells, bradykinin elicited a Ca(2+) influx that was potentiated by the soluble epoxide hydrolase inhibitor, 1 adamantyl-3-cyclohexylurea (ACU), and attenuated by CYP inhibition. Similar effects were observed in cultured endothelial cells overexpressing CYP2C9, but not in CYP2C9-deficient cells, and were prevented by the EET antagonist 14,15 epoxyeicosa-5(Z)-enoic acid as well as by the cAMP antagonist, Rp-cAMPS. The effects on Ca(2+) were mirrored by prolongation of the bradykinin-induced hyperpolarization. Ruthenium red and the combination of charybdotoxin and apamin prevented the latter effect, suggesting that Trp channel activation increases Ca(2+) influx and prolongs the activation of Ca(2+)-dependent K(+) (K(Ca)) channels. Indeed, overexpression of CYP2C9 enhanced the agonist-induced translocation of a TrpC6-V5 fusion protein to caveolin-1-rich areas of the endothelial cell membrane, which was prevented by Rp-cAMPS and mimicked by 11,12 EET. CONCLUSIONS: Elevated EET levels regulate Ca(2+) influx into endothelial cells and the subsequent activation of K(Ca) channels, via a cAMP/PKA-dependent mechanism that involves the intracellular translocation of Trp channels. PMID- 17872453 TI - PECAM-1: a multi-functional molecule in inflammation and vascular biology. AB - Platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31) is a molecule expressed on all cells within the vascular compartment, being expressed to different degrees on most leukocyte sub-types, platelets, and on endothelial cells where its expression is largely concentrated at junctions between adjacent cells. As well as exhibiting adhesive properties, PECAM-1 is an efficient signaling molecule and is now known to have diverse roles in vascular biology including roles in angiogenesis, platelet function, and thrombosis, mechanosensing of endothelial cell response to fluid shear stress, and regulation of multiple stages of leukocyte migration through venular walls. This review will focus on some new developments with respect to the role of PECAM-1 in inflammation and vascular biology, highlighting the emerging complexities associated with the functions of this unique molecule. PMID- 17872454 TI - Hypoxia-induced mediators of stem/progenitor cell trafficking are increased in children with hemangioma. AB - OBJECTIVE: The mechanism of neovascularization during the proliferative phase of infantile hemangioma is poorly understood. It is known that circulating bone marrow-derived endothelial progenitor cells (EPCs) form new blood vessels in ischemic tissues using mediators regulated by the transcription factor, HIF 1alpha. Mobilization of EPCs is enhanced by VEGF-A, matrix metalloproteinase (MMP)-9, and estrogen, whereas homing is secondary to localized expression of stromal cell-derived factor-1alpha (SDF-1alpha). We examined whether these mediators of EPC trafficking are upregulated during the proliferation of infantile hemangioma. METHODS AND RESULTS: Surgical specimens and blood samples were obtained from children with proliferating hemangioma and age-matched controls (n=10, each group). VEGF-A and MMP-9 levels were measured in blood, and tissue sections were analyzed for SDF-1alpha, MMP-9, VEGF-A, and HIF-1alpha. The role of estrogen as a modulator of hemangioma endothelial cell growth was also investigated. We found that all these mediators of EPC trafficking are elevated in blood and specimens from children with proliferating infantile hemangioma. In vitro, the combination of hypoxia and estrogen demonstrated a synergistic effect on hemangioma endothelial cell proliferation. CONCLUSIONS: These findings demonstrate that proliferating hemangiomas express known mediators of vasculogenesis and suggest that this process may play a role in the initiation or progression of this disease. PMID- 17872455 TI - Pioglitazone stimulates apolipoprotein A-I production without affecting HDL removal in HepG2 cells: involvement of PPAR-alpha. AB - OBJECTIVE: Pioglitazone, an antihyperglycemic drug, increases plasma high-density lipoprotein (HDL)-cholesterol in patients with type 2 diabetes. The mechanisms by which pioglitazone regulate HDL levels are not clear. This study examined the effect of pioglitazone on hepatocyte apolipoprotein AI (apoA-I) and apoA-II production and HDL-protein/cholesterol ester uptake. METHODS AND RESULTS: In human hepatoblastoma (HepG2) cells, pioglitazone, dose-dependently (0.5 to 10 micromol/L), increased the de novo synthesis (up to 45%), secretion (up to 44%), and mRNA expression (up to 59%) of apoA-I. Pioglitazone also increased apoA-II de novo synthesis (up to 73%) and mRNA expression (up to 129%). Pioglitazone did not affect the uptake of HDL3-protein or HDL3-cholesterol ester in HepG2 cells. The pioglitazone-induced apoA-I lipoprotein particles increased cholesterol efflux from THP-1 macrophages. The pioglitazone-induced apoA-I secretion or mRNA expression by the HepG2 cells was abrogated with the suppression of PPAR-alpha by small interfering RNA or a specific inhibitor of PPAR-alpha, MK886. CONCLUSIONS: The data indicate that pioglitazone increases HDL by stimulating the de novo hepatic synthesis of apoA-I without affecting hepatic HDL-protein or HDL cholesterol removal. We suggest that pioglitazone-mediated hepatic activation of PPAR-alpha may be one of the mechanisms of action of pioglitazone to raise hepatic apoA-I and HDL. PMID- 17872456 TI - Silencing of a targeted protein in in vivo platelets using a lentiviral vector delivering short hairpin RNA sequence. AB - OBJECTIVE: Because platelets are anucleate cells having a limited life span, direct gene manipulation cannot in principle be used to investigate the involvement of a specific signal transduction pathway in platelet activation. In this study, we examined whether the expression of a short hairpin RNA (shRNA) sequence in hematopoietic stem cells is maintained during megakaryocyte differentiation, thus resulting in inhibition of targeted protein in platelets. METHODS AND RESULTS: To identify platelets derived from transduced stem cells, we generated a lentiviral vector that simultaneously expresses the shRNA sequence driven by the U6 promoter and GFP under the control of the glycoprotein (GP) Ib alpha promoter. Transplantation of mouse bone marrow cells transduced with the vector facilitated specifically mark platelets derived from the transduced cells. Transplantation of cells transduced with shRNA sequence targeting integrin alphaIIb caused a significant reduction of integrin alphaIIb beta3 (alphaIIb beta3) expression in GFP-positive platelets. It also inhibited alphaIIb beta3 activation assessed by the binding of JON/A, an antibody that recognizes activated alphaIIb beta3. Talin-1 silencing by the same method resulted in normal alphaIIb beta3 expression but deficient inside-out alphaIIb beta3 signaling. CONCLUSIONS: shRNA expression driven by the U6 promoter is preserved during megakaryopoiesis. This method facilitates functional analysis of targeted protein in platelet activation. PMID- 17872457 TI - Esculeogenin A, a new tomato sapogenol, ameliorates hyperlipidemia and atherosclerosis in ApoE-deficient mice by inhibiting ACAT. AB - OBJECTIVE: We recently identified esculeoside A, a new spirosolane-type glycoside, with a content in tomatoes that is 4-fold higher than that of lycopene. In the present study, we examined the effects of esculeoside A and esculeogenin A, a new aglycon of esculeoside A, on foam cell formation in vitro and atherogenesis in apoE-deficient mice. METHODS AND RESULTS: Esculeogenin A significantly inhibited the accumulation of cholesterol ester (CE) induced by acetylated low density lipoprotein (acetyl-LDL) in human monocyte-derived macrophages (HMDM) in a dose-dependent manner without inhibiting triglyceride accumulation, however, it did not inhibit the association of acetyl-LDL to the cells. Esculeogenin A also inhibited CE formation in Chinese hamster ovary cells overexpressing acyl-coenzymeA (CoA): cholesterol acyl-transferase (ACAT)-1 or ACAT-2, suggesting that esculeogenin A suppresses the activity of both ACAT-1 and ACAT-2. Furthermore, esculeogenin A prevented the expression of ACAT-1 protein, whereas that of SR-A and SR-BI was not suppressed. Oral administration of esculeoside A to apoE-deficient mice significantly reduced the levels of serum cholesterol, triglycerides, LDL-cholesterol, and the areas of atherosclerotic lesions without any detectable side effects. CONCLUSIONS: Our study provides the first evidence that purified esculeogenin A significantly suppresses the activity of ACAT protein and leads to reduction of atherogenesis. PMID- 17872458 TI - Pathway for differentiation of human embryonic stem cells to vascular cell components and their potential for vascular regeneration. AB - OBJECTIVE: We demonstrated previously that mouse embryonic stem (ES) cell-derived vascular endothelial growth factor receptor-2 (VEGF-R2)-positive cells can differentiate into both vascular endothelial cells and mural cells. This time, we investigated kinetics of differentiation of human ES cells to vascular cells and examined their potential as a source for vascular regeneration. METHODS AND RESULTS: Unlike mouse ES cells, undifferentiated human ES cells already expressed VEGF-R2, but after differentiation, a VEGF-R2-positive but tumor rejection antigen 1-60 (TRA1-60)-negative population emerged. These VEGF-R2-positive but tumor rejection antigen 1-60-negative cells were also positive for platelet derived growth factor receptor alpha and beta chains and could be effectively differentiated into both VE-cadherin+ endothelial cell and alpha-smooth muscle actin+ mural cell. VE-cadherin+ cells, which were also CD34+ and VEGF-R2+ and thought to be endothelial cells in the early differentiation stage, could be expanded while maintaining their maturity. Their transplantation to the hindlimb ischemia model of immunodeficient mice contributed to the construction of new blood vessels and improved blood flow. CONCLUSIONS: We could identify the differentiation process from human ES cells to vascular cell components and demonstrate that expansion and transplantation of vascular cells at the appropriate differentiation stage may constitute a novel strategy for vascular regenerative medicine. PMID- 17872459 TI - Local overexpression of toll-like receptors at the vessel wall induces atherosclerotic lesion formation: synergism of TLR2 and TLR4. AB - OBJECTIVE: Atherosclerosis is now considered as a chronic inflammatory disease, and inflammation is closely related to immune systems, which consist of innate immunity and adaptive-immunity. Recently, toll-like receptors (TLRs) have been identified as key components of innate-immunity. We examined the role of local expressions of TLRs at the vessel wall in atherosclerosis. METHODS AND RESULTS: We transfected cDNA encoding human TLR2 and TLR4 into the carotid arterial vessel wall of rabbits fed high-cholesterol diets with the use of HVJ-liposome. The rabbits were transfected with (1) pCMV-beta-gal, (2) empty vector, (3) TLR2, (4) TLR4, (5) TLR2+4. X-gal staining and immunohistochemical analysis showed that the transfected plasmids were mainly expressed in the media. Neither TLR2 nor TLR4 transfection induced significant augmentation of atherosclerosis. Transfection of TLR2- and TLR4-containing HVJ synergistically accelerated atherosclerosis and increased expressions of vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and MCP-1. Moreover, transfection of TLR2 and TLR4 resulted in synergistic activation of NF-kappaB at the vessel wall in vivo, and in vascular smooth muscle cells in vitro. CONCLUSIONS: Expressions of both TLR2 and TLR4 at the vessel wall synergistically accelerated atherosclerosis. The present study revealed the role of TLRs expressed locally at the vessel wall in the early stage of atherosclerosis. PMID- 17872460 TI - Myofibroblasts induce ectopic activity in cardiac tissue. AB - Focal ectopic activity in cardiac tissue is a key factor in the initiation and perpetuation of tachyarrhythmias. Because myofibroblasts as present in fibrotic remodeled myocardia and infarct scars depolarize cardiomyocytes by heterocellular electrotonic interactions via gap junctions in vitro, we investigated using strands of cultured ventricular cardiomyocytes coated with myofibroblasts, whether this interaction might give rise to depolarization-induced abnormal automaticity. Whereas uncoated cardiomyocyte strands were invariably quiescent, myofibroblasts induced synchronized spontaneous activity in a density dependent manner. Activations appeared at spatial myofibroblast densities >15.7% and involved more than 80% of the preparations at myofibroblast densities of 50%. Spontaneous activity was based on depolarization-induced automaticity as evidenced by: (1) suppression of activity by the sarcolemmal K(ATP) channel opener P-1075; (2) induction of activity in current-clamped single cardiomyocytes undergoing depolarization to potentials similar to those induced by myofibroblasts in cardiomyocyte strands; and (3) induction of spontaneous activity in cardiomyocyte strands coated with connexin 43 transfected Hela cells but not with communication deficient HeLa wild-type cells. Apart from unveiling the mechanism underlying the hallmark of monolayer cultures of cardiomyocytes, ie, spontaneous electromechanical activity, these findings open the perspective that myofibroblasts present in structurally remodeled myocardia following pressure overload and infarction might contribute to arrhythmogenesis by induction of ectopic activity. PMID- 17872461 TI - Sphingosine 1-phosphate receptor 2 negatively regulates neointimal formation in mouse arteries. AB - Neointimal lesion formation was induced in sphingosine 1-phosphate (S1P) receptor 2 (S1P2)-null and wild-type mice by ligation of the left carotid artery. After 28 days, large neointimal lesions developed in S1P2-null but not in wild-type arteries. This was accompanied with a significant increase in both medial and intimal smooth muscle cell (SMC) replication between days 4 to 28, with only minimal replication in wild-type arteries. S1P2-null SMCs showed a significant increase in migration when stimulated with S1P alone and together with platelet derived growth factor, whereas both wild-type and null SMCs migrated equally well to platelet-derived growth factor. S1P increased Rho activation in wild-type but not in S1P2-null SMCs, and inhibition of Rho activity promoted S1P-induced SMC migration. Plasma S1P levels were similar and did not change after surgery. These results suggest that activation of S1P2 normally acts to suppress SMC growth in arteries and that S1P is a regulator of neointimal development. PMID- 17872462 TI - Transient receptor potential channel 6-mediated, localized cytosolic [Na+] transients drive Na+/Ca2+ exchanger-mediated Ca2+ entry in purinergically stimulated aorta smooth muscle cells. AB - The Na+/Ca2+ exchanger (NCX) is increasingly recognized as a physiological mediator of Ca2+ influx and significantly contributes to salt-sensitive hypertension. We recently reported that Ca2+ influx by the NCX (1) is the primary mechanism of Ca2+ entry in purinergically stimulated rat aorta smooth muscle cells and (2) requires functional coupling with transient receptor potential channel 6 nonselective cation channels. Using the Na+ indicator CoroNa Green, we now directly observed and characterized the localized cytosolic [Na+] ([Na+]i) elevations that have long been hypothesized to underlie physiological NCX reversal but that have never been directly shown. Stimulation of rat aorta smooth muscle cells caused both global and monotonic [Na+]i elevations and localized [Na+]i transients (LNats) at the cell periphery. Inhibition of nonselective cation channels with SKF-96365 (50 micromol/L) and 2-amino-4-phosphonobutyrate (75 micromol/L) reduced both global and localized [Na+]i elevations in response to ATP (1 mmol/L). This effect was mimicked by expression of a dominant negative construct of transient receptor potential channel 6. Selective inhibition of NCX mediated Ca2+ entry with KB-R7943 (10 micromol/L) enhanced the LNats, whereas the global cytosolic [Na+] signal was unaffected. Inhibition of mitochondrial Na+ uptake with CGP-37157 (10 micromol/L) increased both LNats and global cytosolic [Na+] elevations. These findings directly demonstrate NCX regulation by LNats, which are restricted to subsarcolemmal, cytoplasmic microdomains. Analysis of the LNats, which facilitate Ca2+ entry via NCX, suggests that mitochondria limit the cytosolic diffusion of LNats generated by agonist-mediated activation of transient receptor potential channel 6-containing channels. PMID- 17872463 TI - Overexpression of FK-506 binding protein 12.0 modulates excitation contraction coupling in adult rabbit ventricular cardiomyocytes. AB - The effect of the 12-kDa isoform of FK-506-binding protein (FKBP)12.0 on cardiac excitation-contraction coupling was studied in adult rabbit ventricular myocytes after transfection with a recombinant adenovirus coding for human FKBP12.0 (Ad FKBP12.0). Western blots confirmed overexpression (by 2.6+/-0.4 fold, n=5). FKBP12.0 association with rabbit cardiac ryanodine receptor (RyR2) was not detected by immunoprecipitation. However, glutathione S-transferase pull-down experiments indicated FKBP12.0-RyR2 binding to proteins isolated from human and rabbit but not dog myocardium. Voltage-clamp experiments indicated no effects of FKBP12.0 overexpression on L-type Ca2+ current (I(Ca,L)) or Ca2+ efflux rates via the Na+/Ca2+ exchanger. Ca2+ transient amplitude was also not significantly different. However, sarcoplasmic reticulum Ca2+ load was approximately 25% higher in myocytes in the Ad-FKBP12.0 group. The reduced ability of I(Ca,L) to initiate sarcoplasmic reticulum Ca2+ release was observed over a range of values of sarcoplasmic reticulum Ca2+ content, indicating that overexpression of FKBP12.0 reduces the sensitivity of RyR2 to Ca2+. Ca2+ spark morphology was measured in beta-escin-permeabilized cardiomyocytes. Ca2+ spark amplitude and duration were significantly increased, whereas frequency was decreased in cells overexpressing FKBP12.0. These changes were accompanied by an increased sarcoplasmic reticulum Ca2+ content. In summary, the effects of FKBP12.0 overexpression on intact and permeabilized cells were similar to those of tetracaine, a drug known to reduce RyR2 Ca2+ sensitivity and distinctly different from the effects of overexpression of the FKBP12.6 isomer. In conclusion, FKBP12.0-RyR2 interaction can regulate the gain of excitation-contraction coupling. PMID- 17872464 TI - Increased atherosclerotic lesion calcification in a novel mouse model combining insulin resistance, hyperglycemia, and hypercholesterolemia. AB - No mouse model is currently available where the induction of type 2 diabetes on an atherosclerotic background could be achieved without significant concomitant changes in plasma lipid levels. We crossbred 2 genetically modified mouse strains to achieve a model expressing both atherosclerosis and characteristics of type 2 diabetes. For atherosclerotic background we used low-density lipoprotein receptor deficient mice synthetizing only apolipoprotein B100 (LDLR(-/-) ApoB(100/100)). Diabetic background was obtained from transgenic mice overexpressing insulin-like growth factor-II (IGF-II) in pancreatic beta cells. Thorough phenotypic characterization was performed in 6- and 15-month-old mice on both normal and high-fat Western diet. Results indicated that IGF-II transgenic LDLR(-/ )ApoB(100/100) mice demonstrated insulin resistance, hyperglycemia, and mild hyperinsulinemia compared with hypercholesterolemic LDLR(-/-)ApoB(100/100) controls. In addition, old IGF-II/LDLR(-/-)ApoB(100/100) mice displayed significantly increased lesion calcification, which was more related to insulin resistance than glucose levels, and significantly higher baseline expression in aorta of several genes related to calcification and inflammation. Lipid levels of IGF-II/LDLR(-/-)ApoB(100/100) mice did not differ from LDLR(-/-)ApoB(100/100) controls at any time. In conclusion, type 2 diabetic factors induce increased calcification and lesion progression without any lipid changes in a new mouse model of diabetic macroangiopathy. PMID- 17872465 TI - Acid-sensing ion channels contribute to transduction of extracellular acidosis in rat carotid body glomus cells. AB - Carotid body chemoreceptors sense hypoxemia, hypercapnia, and acidosis and play an important role in cardiorespiratory regulation. The molecular mechanism of pH sensing by chemoreceptors is not clear, although it has been proposed to be mediated by a drop in intracellular pH of carotid body glomus cells, which inhibits a K+ current. Recently, pH-sensitive ion channels have been described in glomus cells that respond directly to extracellular acidosis. In this study, we investigated the possible molecular mechanisms of carotid body pH sensing by recording the responses of glomus cells isolated from rat carotid body to rapid changes in extracellular pH using the whole-cell patch-clamping technique. Extracellular acidosis evoked transient inward current in glomus cells that was inhibited by the acid-sensing ion channel (ASIC) blocker amiloride, absent in Na+ free bathing solution, and enhanced by either Ca2+-free buffer or addition of lactate. In addition, ASIC1 and ASIC3 were shown to be expressed in rat carotid body by quantitative PCR and immunohistochemistry. In the current-clamp mode, extracellular acidosis evoked both a transient and sustained depolarizations. The initial transient component of depolarization was blocked by amiloride, whereas the sustained component was eliminated by removal of K+ from the pipette solution and partially blocked by the TASK (tandem-p-domain, acid-sensitive K+ channel) blockers anandamide and quinidine. The results provide the first evidence that ASICs may contribute to chemotransduction of low pH by carotid body chemoreceptors and that extracellular acidosis directly activates carotid body chemoreceptors through both ASIC and TASK channels. PMID- 17872466 TI - Ets-1 is a critical transcriptional regulator of reactive oxygen species and p47(phox) gene expression in response to angiotensin II. AB - Angiotensin (Ang) II is a potent mediator of vascular inflammation. A central mechanism by which Ang II promotes inflammation is through the generation of reactive oxygen species (ROS). In the current study, we investigated the role of the transcription factor Ets-1 in regulating Ang II-induced ROS generation. ROS generation was measured in the thoracic aorta of Ets-1(-/-) mice compared with littermate controls after continuous infusion of Ang II. H2O2 and superoxide anion (O2(-)) production were significantly blunted in the Ets-1(-/-) mice. Inhibition of Ets-1 expression by small interfering RNA in primary human aortic smooth muscle cells also potently inhibited ROS production and the induction of the NAD(P)H oxidase subunit p47(phox) in response to Ang II. To evaluate the therapeutic potential of inhibiting Ets-1 in wild-type mice, dominant negative Ets-1 membrane-permeable peptides were administered systemically. Ang II-induced ROS production and medial hypertrophy in the thoracic aorta were markedly diminished as a result of blocking Ets-1. In summary, Ets-1 functions as a critical downstream transcriptional mediator of Ang II ROS generation by regulating the expression of NAD(P)H oxidase subunits such as p47(phox). PMID- 17872467 TI - Arrhythmogenic mechanisms in a mouse model of catecholaminergic polymorphic ventricular tachycardia. AB - Catecholaminergic polymorphic ventricular tachycardia (VT) is a lethal familial disease characterized by bidirectional VT, polymorphic VT, and ventricular fibrillation. Catecholaminergic polymorphic VT is caused by enhanced Ca2+ release through defective ryanodine receptor (RyR2) channels. We used epicardial and endocardial optical mapping, chemical subendocardial ablation with Lugol's solution, and patch clamping in a knockin (RyR2/RyR2(R4496C)) mouse model to investigate the arrhythmogenic mechanisms in catecholaminergic polymorphic VT. In isolated hearts, spontaneous ventricular arrhythmias occurred in 54% of 13 RyR2/RyR2(R4496C) and in 9% of 11 wild-type (P=0.03) littermates perfused with Ca2+and isoproterenol; 66% of 12 RyR2/RyR2(R4496C) and 20% of 10 wild-type hearts perfused with caffeine and epinephrine showed arrhythmias (P=0.04). Epicardial mapping showed that monomorphic VT, bidirectional VT, and polymorphic VT manifested as concentric epicardial breakthrough patterns, suggesting a focal origin in the His-Purkinje networks of either or both ventricles. Monomorphic VT was clearly unifocal, whereas bidirectional VT was bifocal. Polymorphic VT was initially multifocal but eventually became reentrant and degenerated into ventricular fibrillation. Endocardial mapping confirmed the Purkinje fiber origin of the focal arrhythmias. Chemical ablation of the right ventricular endocardial cavity with Lugol's solution induced complete right bundle branch block and converted the bidirectional VT into monomorphic VT in 4 anesthetized RyR2/RyR2(R4496C) mice. Under current clamp, single Purkinje cells from RyR2/RyR2(R4496C) mouse hearts generated delayed afterdepolarization-induced triggered activity at lower frequencies and level of adrenergic stimulation than wild-type. Overall, the data demonstrate that the His-Purkinje system is an important source of focal arrhythmias in catecholaminergic polymorphic VT. PMID- 17872468 TI - Clinically relevant models of diabetic cardiac complications. PMID- 17872469 TI - Gain and cardiac E-C coupling: revisited and revised. PMID- 17872470 TI - Substrate matters: reciprocally stimulatory integrin and VEGF signaling in endothelial cells. PMID- 17872471 TI - Linking calsequestrin to lumenal control of SR Ca2+ release. PMID- 17872472 TI - Interferon-gamma and intimal hyperplasia. PMID- 17872473 TI - Leptin signaling and obesity: cardiovascular consequences. AB - Leptin, among the best known hormone markers for obesity, exerts pleiotropic actions on multiple organ systems. In this review, we summarize major leptin signaling pathways, namely Janus-activated kinase/signal transducers and activators of transcription and mitogen-activated protein kinase, including possible mechanisms of leptin resistance in obesity. The effects of leptin on the cardiovascular system are discussed in detail, including its contributions to hypertension, atherosclerosis, depressed myocardial contractile function, fatty acid metabolism, hypertrophic remodeling, and reduction of ischemic/reperfusion injury. The overall goal is to summarize current understanding of how altered leptin signaling in obesity contributes to obesity-related cardiovascular disease. PMID- 17872474 TI - Asymptomatic Moyamoya disease. PMID- 17872475 TI - Prognosis and safety of anticoagulation in intracranial artery dissections in adults. PMID- 17872476 TI - Cerebral blood flow changes in elderly hypertensive patients and cognitive functions. PMID- 17872477 TI - Managing hyperglycemia in acute ischemic stroke patients. PMID- 17872478 TI - The seven wonders of China in stroke therapy: fact or illusion? PMID- 17872479 TI - Definition of metabolic syndrome. PMID- 17872480 TI - Clinical grading scales in spontaneous intracerebral hemorrhage. PMID- 17872481 TI - About hyperglycemia during acute stroke. PMID- 17872482 TI - Asymptomatic carotid stenosis. PMID- 17872483 TI - Cerebrovascular events in individuals with asymptomatic carotid disease. PMID- 17872484 TI - Informed consent in acute stroke. PMID- 17872485 TI - Effect of hand splinting: isn't temporality crucial? PMID- 17872486 TI - Acetaminophen for temperature reduction in acute stroke: potential but unproven benefits. PMID- 17872488 TI - Influence of an endotracheal tube with polyurethane cuff and subglottic secretion drainage on pneumonia. AB - RATIONALE: Subglottic secretion drainage (SSD) appears to be effective in preventing ventilator-associated pneumonia (VAP), primarily by reducing early onset pneumonia; but it may not prevent late-onset pneumonia. We tested the hypothesis using an endotracheal tube incorporating an ultrathin polyurethane cuff (which reduces channel formation and fluid leakage from the subglottic area), in addition to an SSD lumen, which would reduce the incidence of late onset VAP. OBJECTIVES: To compare the incidence of VAP, using an endotracheal tube with polyurethane cuff and subglottic secretion drainage (ETT-PUC-SSD) versus a conventional endotracheal tube (ETT-C) with polyvinyl cuff, without subglottic secretion drainage. METHODS: Clinical randomized trial in a 24-bed medical-surgical intensive care unit. Patients expected to require mechanical ventilation for more than 24 hours were randomly assigned to one of two groups: one was ventilated with ETT-PUC-SSD and the other with ETT-C. MEASUREMENTS AND MAIN RESULTS: Tracheal aspirate samples were obtained during endotracheal intubation, then twice per week and finally on extubation. VAP was found in 31 of 140 (22.1%) patients in the ETT-C group and in 11 of 140 (7.9%) in the ETT-PUC SSD group (P = 0.001). Cox regression analysis showed ETT-C as a risk factor for global VAP (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.66-6.67; P = 0.001), early-onset VAP (HR, 3.3; 95% CI, 1.19-9.09; P = 0.02), and late-onset VAP (HR, 3.5; 95% CI, 1.34-9.01; P = 0.01). CONCLUSIONS: The use of an endotracheal tube with polyurethane cuff and subglottic secretion drainage helps prevent early- and late-onset VAP. Clinical trial registered with www.clinicaltrials.gov (NCT 00475579). PMID- 17872487 TI - Inhaled agonists of soluble guanylate cyclase induce selective pulmonary vasodilation. AB - RATIONALE: Nitric oxide-independent agonists of soluble guanylate cyclase (sGC) have been developed. OBJECTIVES: We tested whether inhalation of novel dry-powder microparticle formulations containing sGC stimulators (BAY 41-2272, BAY 41-8543) or an sGC activator (BAY 58-2667) would produce selective pulmonary vasodilation in lambs with acute pulmonary hypertension. We also evaluated the combined administration of BAY 41-8543 microparticles and inhaled nitric oxide (iNO). Finally, we examined whether inhaling BAY 58-2667 microparticles would produce pulmonary vasodilation when the response to iNO is impaired. METHODS: In awake, spontaneously breathing lambs instrumented with vascular catheters and a tracheostomy tube, U-46619 was infused intravenously to increase mean pulmonary arterial pressure to 35 mm Hg. MEASUREMENTS AND MAIN RESULTS: Inhalation of microparticles composed of either BAY 41-2272, BAY 41-8543, or BAY 58-2667 and excipients (dipalmitoylphosphatidylcholine, albumin, lactose) produced dose dependent pulmonary vasodilation and increased transpulmonary cGMP release without significant effect on mean arterial pressure. Inhalation of microparticles containing BAY 41-8543 or BAY 58-2667 increased systemic arterial oxygenation. The magnitude and duration of pulmonary vasodilation induced by iNO were augmented after inhaling BAY 41-8543 microparticles. Intravenous administration of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), which oxidizes the prosthetic heme group of sGC, markedly reduced the pulmonary vasodilator effect of iNO. In contrast, pulmonary vasodilation and transpulmonary cGMP release induced by inhaling BAY 58-2667 microparticles were greatly enhanced after treatment with ODQ. CONCLUSIONS: Inhalation of microparticles containing agonists of sGC may provide an effective novel treatment for patients with pulmonary hypertension, particularly when responsiveness to iNO is impaired by oxidation of sGC. PMID- 17872489 TI - Prevalence and impact of bronchiectasis in alpha1-antitrypsin deficiency. AB - RATIONALE: alpha(1)-Antitrypsin (AAT) deficiency is associated with increased risk of chronic obstructive pulmonary disease (COPD), in particular emphysema, but airway disease is less well described. OBJECTIVES: To assess the prevalence of airways disease in subjects with AAT deficiency and to identify the relationship between radiological airway abnormalities and clinical phenotype. METHODS: We characterized the computed tomographic phenotype of 74 subjects (PiZ), using visual scoring of airway disease and densitometric assessment of emphysema. Computed tomographic measurements were related to physiology, health status (St. George's Respiratory Questionnaire), and emphysema severity, and the relative impact of airway disease and emphysema severity on health status and airflow obstruction was compared by stepwise regression. MEASUREMENTS AND MAIN RESULTS: Bronchiectatic changes were seen in 70 subjects, and a subgroup with a bronchiectasis-predominant phenotype was identified. Clinically significant bronchiectasis (radiologic bronchiectasis in 4 or more bronchopulmonary segments together with symptoms of regular sputum production) occurred in 20 subjects (27%). AAT-deficient index cases had higher airway disease scores (P < 0.05), more severe emphysema (P < 0.001), and greater impairment of physiology (P < 0.001) and health status (P < 0.05) than nonindex cases. Airway disease scores correlated with health status, and bronchial wall thickening correlated with FEV(1). Regression analysis indicated that emphysema severity had the strongest associations for health status (r = 0.505, P < 0.001) and FEV(1) (r = 0.699, P < 0.001), but the addition of airway disease score improved the regression models (r = 0.596, P = 0.002 and r = 0.783, P < 0.001, respectively). CONCLUSIONS: Emphysema is the predominant component of COPD in AAT deficiency, but the prevalence and impact of airway disease are greater than currently recognized. Consequently, future therapeutic strategies in AAT deficiency should also target this component of COPD. PMID- 17872490 TI - The healthy worker effect in asthma: work may cause asthma, but asthma may also influence work. AB - Despite the increasing attention to the relationship between asthma and work exposures, occupational asthma remains underrecognized and its population burden underestimated. This may be due, in part, to the fact that traditional approaches to studying asthma in populations cannot adequately take into account the healthy worker effect (HWE). The HWE is the potential bias caused by the phenomenon that sicker individuals may choose work environments in which exposures are low; they may be excluded from being hired; or once hired, they may seek transfer to less exposed jobs or leave work. This article demonstrates that population- and workplace-based asthma studies are particularly subject to HWE bias, which leads to underestimates of relative risks. Our objective is to describe the HWE as it relates to asthma research, and to discuss the significance of taking HWE bias into account in designing and interpreting asthma studies. We also discuss the importance of understanding HWE bias for public health practitioners and for clinicians. Finally, we emphasize the timeliness of this review in light of the many longitudinal "child to young adult" asthma cohort studies currently underway. These prospective studies will soon provide an ideal opportunity to examine the impact of early workplace environments on asthma in young adults. We urge occupational and childhood asthma epidemiologists collaborate to ensure that this opportunity is not lost. PMID- 17872491 TI - Asymmetric dimethylarginine is increased in chronic thromboembolic pulmonary hypertension. AB - RATIONALE: Asymmetric dimethylarginine (ADMA), a potent endogenous nitric oxide synthase (NOS) inhibitor, is increased in idiopathic pulmonary arterial hypertension and associated with unfavorable outcome. OBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH), although principally amenable to surgical removal of major pulmonary arterial obstructions by pulmonary endarterectomy, may show a small-vessel pulmonary arteriopathy similar to idiopathic pulmonary arterial hypertension. We hypothesized that ADMA plasma levels are increased in patients with CTEPH. METHODS: We measured ADMA by high performance liquid chromatography at the time of diagnosis in 135 patients with CTEPH. Inoperability in 66 patients was based on an imbalance between severity of pulmonary hypertension and morphologic lesions. MEASUREMENTS AND MAIN RESULTS: ADMA plasma levels were significantly elevated in patients, compared with 40 matched control subjects (0.62 [0.51-0.73] vs. 0.51 [0.45-0.6] micromol/L, P = 0.0002). At baseline, ADMA plasma concentrations correlated with mixed venous saturation (r = -0.25, P = 0.005), right atrial pressure (r = 0.35, P < 0.0001), and cardiac index (r = -0.21, P = 0.01). Patients who underwent surgery demonstrated lower ADMA levels at baseline than inoperable patients (0.60 [0.5 0.68] vs. 0.63 [0.53-0.85] micromol/L, P = 0.02), with a further decrease 12 +/- 1 months after pulmonary endarterectomy (P = 0.02). Endothelial NOS expression in endothelial cells was low in patients with elevated ADMA plasma levels. Survival of patients with ADMA plasma levels >/= 0.64 micromol/L was worse than in patients with ADMA plasma levels < 0.64 micromol/L. CONCLUSIONS: ADMA plasma levels correlate with the severity of pulmonary vascular disease and predict outcome in patients with CTEPH. Measurement of ADMA plasma levels may be useful for estimating the degree of small-vessel arteriopathy in CTEPH. PMID- 17872492 TI - Clinical use of Ibuprofen is associated with slower FEV1 decline in children with cystic fibrosis. AB - RATIONALE: High-dose ibuprofen in a 4-year controlled trial slowed FEV(1) decline in young subjects with cystic fibrosis, but the effectiveness of ibuprofen has not been assessed in a large group of patients treated clinically with this therapy. OBJECTIVES: To assess the effect of ibuprofen therapy on FEV(1) decline in children and adolescents with cystic fibrosis, using observational data from the Cystic Fibrosis Foundation Patient Registry. METHODS: The rate of decline in FEV(1) percent predicted over 2-7 years among patients age 6-17 years with FEV(1) > 60% predicted, and who were treated with ibuprofen (1,365), was compared with patients of similar age and disease severity who were not treated with this therapy (8,960). Multilevel repeated-measures mixed-regression models were used to estimate rates of decline, adjusting for characteristics and therapies that influenced FEV(1) decline. Adverse effects were compared among those treated versus not treated with ibuprofen. MEASUREMENTS AND MAIN RESULTS: FEV(1) declined less rapidly among patients treated with ibuprofen (difference, 0.60% predicted per year; 95% confidence interval, 0.31 to 0.89; P < 0.0001); a 29% reduction in slope based on an average decline of 2.08% predicted per year for patients not treated. Those treated with ibuprofen were more likely to have an episode of gastrointestinal bleeding requiring hospitalization, but the occurrence was rare in both groups (annual incidence, 0.37 vs. 0.14%; relative risk, 2.72; P < 0.001). CONCLUSIONS: Slower rates of FEV(1) decline are seen in children and adolescents with cystic fibrosis who are treated with ibuprofen. The apparent benefits of ibuprofen therapy outweigh the small risk of gastrointestinal bleeding. PMID- 17872493 TI - A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. AB - RATIONALE: Accumulation of eosinophils in the bronchial mucosa of individuals with asthma is considered to be a central event in the pathogenesis of asthma. In animal models, airway eosinophil recruitment and airway hyperresponsiveness in response to allergen challenge are reduced by specific targeting of interleukin 5. A previous small dose-finding study found that mepolizumab, a humanized anti interleukin-5 monoclonal antibody, had no effect on allergen challenge in humans. OBJECTIVES: To investigate the effect of three intravenous infusions of mepolizumab, 250 or 750 mg at monthly intervals, on clinical outcome measures in 362 patients with asthma experiencing persistent symptoms despite inhaled corticosteroid therapy (400-1,000 mug of beclomethasone or equivalent). METHODS: Multicenter, randomized, double-blind, placebo-controlled study. MEASUREMENTS AND MAIN RESULTS: Morning peak expiratory flow, forced expiratory volume in 1 second, daily beta(2)-agonist use, symptom scores, exacerbation rates, and quality of life measures. Sputum eosinophil levels were also measured in a subgroup of 37 individuals. Mepolizumab was associated with a significant reduction in blood and sputum eosinophils in both treatment groups (blood, P < 0.001 for both doses; sputum, P = 0.006 for 250 mg and P = 0.004 for 750 mg). There were no statistically significant changes in any of the clinical end points measured. There was a nonsignificant trend for decrease in exacerbation rates in the mepolizumab 750-mg treatment group (P = 0.065). CONCLUSIONS: Mepolizumab treatment does not appear to add significant clinical benefit in patients with asthma with persistent symptoms despite inhaled corticosteroid therapy. Further studies are needed to investigate the effect of mepolizumab on exacerbation rates, using protocols specifically tailored to patients with asthma with persistent airway eosinophilia. PMID- 17872494 TI - EET displays anti-inflammatory effects in TNF-alpha stimulated human bronchi: putative role of CPI-17. AB - The aim of the present study was to investigate the anti-inflammatory effects of 14,15-epoxyeicosatrienoic acid (EET) on reactivity and Ca(2+) sensitivity in TNF alpha-stimulated human bronchi. Tension measurements performed on either control, TNF-alpha-, or TNF-alpha + EET-pretreated bronchi revealed that 100 nM 14,15-EET pretreatments significantly reduced the reactivity of TNF-alpha-pretreated tissues to contractile agonists. EET also normalized the relaxing response to isoproterenol in TNF-alpha-treated bronchi. Pretreatment with 100 nM 14,15-EET prevented TNF-alpha-induced IkappaBalpha degradation, as demonstrated by an increase in IkappaBalpha protein levels on Western blot analysis. The anti inflammatory properties of EET were mediated by the inhibition of IkappaBalpha degradation, suggesting a lower activation of NF-kappaB. The Ca(2+) sensitivity of TNF-alpha-stimulated bronchi was also evaluated on beta-escin-permeabilized preparations. Observed mean responses demonstrated that EET pretreatments abolished Ca(2+) hypersensitivity developed by TNF-alpha-stimulated bronchial explants. Moreover, 14,15-EET significantly reduced PDBu-induced Ca(2+) sensitivity in TNF-alpha-stimulated bronchi. Western blot and RT-PCR analyses revealed that CPI-17 protein and transcript levels were increased in TNF-alpha treated bronchi, as opposed to being decreased in the presence of 14,15-EET. This eicosanoid also reduced U-46619-induced Ca(2+) sensitivity, which is related to the activation of Rho-kinase pathway. These results were also correlated with an increase in protein staining and transcription level of p116(Rip), a RhoA inhibitory-binding protein. Altogether, these data demonstrate that 14,15-EET is a potent modulator of the hyperreactivity triggered by TNF-alpha in human airway smooth muscle cells. PMID- 17872495 TI - HGF mediates cell proliferation of human mesothelioma cells through a PI3K/MEK5/Fra-1 pathway. AB - The ligand hepatocyte growth factor/scatter factor (HGF) and its receptor tyrosine kinase, c-Met, are highly expressed in most human malignant mesotheliomas (MMs) and may contribute to their increased growth and viability. Based upon our observation that RNA silencing of fos-related antigen 1 (Fra-1) inhibited c-met expression in rat mesotheliomas (1), we hypothesized that Fra-1 was a key player in HGF-induced proliferation in human MMs. In three of seven human MM lines evaluated, HGF increased Fra-1 levels and phosphorylation of both extracellular signal-regulated kinase 5 (ERK5) and AKT that were inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor, LY290042. HGF-dependent phosphorylation and Fra-1 expression were decreased after knockdown of Fra-1, whereas overexpression of Fra-1 blocked the expression of mitogen/extracellular signal-regulated kinase kinases (MEK)5 at the mRNA and protein levels. Stable MM cell lines using a dnMEK5 showed that basal Fra-1 levels were increased in comparison to empty vector control lines. HGF also caused increased MM cell viability and proliferating cell nuclear antigen (PCNA) expression that were abolished by knockdown of MEK5 or Fra-1. Data suggest that HGF-induced effects in some MM cells are mediated via activation of a novel PI3K/ERK5/Fra-1 feedback pathway that might explain tumor-specific effects of c-Met inhibitors on MM and other tumors. PMID- 17872497 TI - Cigarette smoke exposure attenuates cytokine production by mouse alveolar macrophages. AB - Alveolar macrophages (aMs) play a central role in respiratory host defense by sensing microbial antigens and initiating immune-inflammatory responses early in the course of an infection. The purpose of this study was to investigate the effect of cigarette smoke exposure on aMs after stimulation of innate pattern recognition receptors (PRRs) in a murine model. To accomplish this, C57BL/6 mice were exposed for 8 weeks using two models of cigarette smoke exposure, nose-only or whole-body exposure, and aMs isolated from the bronchoalveolar lavage. After stimulation of aMs with pI:C, a mimic of viral replication, and bacterial cell wall constituent LPS, aMs from cigarette smoke-exposed mice produced significantly attenuated levels of the inflammatory cytokines TNF-alpha and IL-6, and the chemokine RANTES. This attenuation was specific to the aM compartment, and not related to changes in aM viability or expression of Toll-like receptor (TLR)3 or TLR4 between groups. Furthermore, aMs from smoke-exposed mice had decreased cytokine RNA as compared with aMs from sham-exposed mice. Mechanistically, this was associated with decreased nuclear translocation of the proinflammatory transcription factor NF-kappaB, and increased activator protein-1 nuclear translocation, in aMs from smoke-exposed mice. Attenuated cytokine production was reversible after smoking cessation. Cigarette smoke exposure also attenuated TNF-alpha production after stimulation with nucleotide-oligomerization domain-like receptor agonists, showing that the effect applies more broadly to other PRR pathways. Our data demonstrate that cigarette smoke exposure attenuates aM responses after innate stimulation, including pathways typically associated with bacterial and viral infections. PMID- 17872496 TI - Effects of KGF on alveolar epithelial cell transdifferentiation are mediated by JNK signaling. AB - Rat alveolar epithelial cells (AEC) in primary culture transdifferentiate from a type II (AT2) toward a type I (AT1) cell-like phenotype, a process that can be both prevented and reversed by keratinocyte growth factor (KGF). Microarray analysis revealed that these effects of KGF are associated with up-regulation of key molecules in the mitogen-activated protein kinase (MAPK) pathway. To further explore the role of three key MAPK (i.e., extracellular signal-related kinase [ERK] 1/2, c-Jun N-terminal kinase [JNK] and p38) in mediating effects of KGF on AEC phenotype, primary rat AEC cultivated in minimal defined serum-free medium (MDSF) were treated with KGF (10 ng/ml) from Day 4 for intervals up to 48 hours. Exposure to KGF activated all three MAPK, JNK, ERK1/2, and p38. Inhibition of JNK, but not of ERK1/2 or p38, abrogated the ability of KGF to maintain the AT2 cell phenotype, as evidenced by loss of expression of lamellar membrane protein (p180) and increased reactivity with the AT1 cell-specific monoclonal antibody VIIIB2 by Day 6 in culture. Overexpression of JNKK2, upstream kinase of JNK, increased activation of endogenous c-Jun in association with increased expression of p180 and abrogation of AQP5, suggesting that activation of c-Jun promotes retention of the AT2 cell phenotype. These results indicate that retention of the AT2 cell phenotype by KGF involves c-Jun and suggest that activation of c-Jun kinase may be an important determinant of maintenance of AT2 cell phenotype. PMID- 17872498 TI - TGF-beta suppresses EGF-induced MAPK signaling and proliferation in asthmatic epithelial cells. AB - Epithelial damage is an important pathophysiologic feature of asthma. Bronchial epithelium damage results in release of growth factors such as transforming growth factor (TGF)-beta(1) that may affect epithelial cell proliferation. The objective of our study is to evaluate the importance of TGF-beta(1) in regulating epithelial cell repair in asthma. We evaluated the effect of TGF-beta(1) on epidermal growth factor (EGF)-induced proliferation and downstream signaling in epithelial cells obtained from subjects with asthma compared with cells from healthy subjects. Cell proliferation was evaluated by bromodeoxyuridine incorporation. EGF receptor (EGFR), mitogen-activated protein kinase, TGF-beta receptors, Smads, Smad anchor for receptor activation (SARA), and cyclin dependant kinase inhibitors were evaluated by Western blot. TGF-beta(1) and receptor expression were measured by RT-PCR and by enzyme-linked immunosorbent assay. Proliferation of epithelial cells at baseline and after EGF stimulation was significantly reduced in cells derived from subjects with asthma compared with cells obtained from healthy control subjects. EGF-induced ERK1/2 phosphorylation was reduced in epithelial cells from subjects with asthma compared with cells from healthy control subjects. This was paralleled with a reduced EGFR phosphorylation. Addition of TGF-beta(1) significantly decreased EGF induced cell proliferation. TGF-beta(1) production was higher in asthmatic epithelial cells compared with normal cells. This was supported by a high expression of pSmad 3 and SARA in cells derived from individuals with asthma compared with normal subjects. Cycline-dependent kinase inhibitors were highly expressed in asthmatic compared with normal cells. Inhibition of TGF-beta(1) signaling in asthmatic epithelial cells restored EGFR, ERK1/2 phosphorylation, and cell proliferation induced by EGF. Our results suggest that TGF-beta restrains EGFR phosphorylation and downstream signaling in bronchial epithelial cells. PMID- 17872499 TI - Functional sarcoplasmic reticulum for calcium handling of human embryonic stem cell-derived cardiomyocytes: insights for driven maturation. AB - Cardiomyocytes (CMs) are nonregenerative. Self-renewable pluripotent human embryonic stem cells (hESCs) can differentiate into CMs for cell-based therapies. In adult CMs, Ca(2+)-induced Ca(2+) release from the sarcoplasmic reticulum (SR) via the ryanodine receptor (RyR) is key in excitation-contraction coupling. Therefore, proper Ca(2+) handling properties of hESC-derived CMs are required for their successful functional integration with the recipient heart. Here, we performed a comprehensive analysis of CMs differentiated from the H1 (H1-CMs) and HES2 (HES2-CMs) hESC lines and human fetal (F) and adult (A) left ventricular (LV) CMs. Upon electrical stimulation, all of H1-, HES2-, and FLV-CMs generated similar Ca(2+) transients. Caffeine induced Ca(2+) release in 65% of FLV-CMs and approximately 38% of H1- and HES2-CMs. Ryanodine significantly reduced the electrically evoked Ca(2+) transient amplitudes of caffeine-responsive but not insensitive HES2- and H1-CMs and slowed their upstroke; thapsigargin, which inhibits the sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) pump, reduced the amplitude of only caffeine-responsive HES2- and H1-CMs and slowed the decay. SERCA2a expression was highest in ALV-CMs but comparable among H1-, HES2-, and FLV-CMs. The Na(+)-Ca(2+) exchanger was substantially expressed in both HES2- and H1-CMs relative to FLV- and ALV-CMs. RyR was expressed in HES2-, H1-, and FLV CMs, but the organized pattern for ALV-CMs was not observed. The regulatory proteins junctin, triadin, and calsequestrin were expressed in ALV-CMs but not HES2- and H1-CMs. We conclude that functional SRs are indeed expressed in hESC CMs, albeit immaturely. Our results may lead to driven maturation of Ca(2+) handling properties of hESC-CMs for enhanced contractile functions. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17872500 TI - Fas transduces dual apoptotic and trophic signals in hematopoietic progenitors. AB - Stem cells and progenitors are often required to realize their differentiation potential in hostile microenvironments. The Fas/Fas ligand (FasL) interaction is a major effector pathway of apoptosis, which negatively regulates the expansion of differentiated hematopoietic cells. The involvement of this molecular interaction in the function of hematopoietic stem and progenitor cells is not well understood. In the murine syngeneic transplant setting, both Fas and FasL are acutely upregulated in bone marrow-homed donor cells; however, the Fas(+) cells are largely insensitive to FasL-induced apoptosis. In heterogeneous populations of lineage-negative (lin(-)) bone marrow cells and progenitors isolated by counterflow centrifugal elutriation, trimerization of the Fas receptor enhanced the clonogenic activity. Inhibition of caspases 3 and 8 did not affect the trophic signals mediated by Fas, yet it efficiently blocked the apoptotic pathways. Fas-mediated tropism appears to be of physiological significance, as pre-exposure of donor cells to FasL improved the radioprotective qualities of hematopoietic progenitors, resulting in superior survival of myeloablated hosts. Under these conditions, the activity of long-term reconstituting cells was not affected, as determined in sequential secondary and tertiary transplants. Dual caspase-independent tropic and caspase-dependent apoptotic signaling place the Fas receptor at an important junction of activation and death. This regulatory mechanism of hematopoietic homeostasis activates progenitors to promote the recovery from aplasia and converts into a negative regulator in distal stages of cell differentiation. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17872501 TI - Chondrogenic potential of human adult mesenchymal stem cells is independent of age or osteoarthritis etiology. AB - Osteoarthritis (OA) is a multifactorial disease strongly correlated with history of joint trauma, joint dysplasia, and advanced age. Mesenchymal stem cells (MSCs) are promising cells for biological cartilage regeneration. Conflicting data have been published concerning the availability of MSCs from the iliac crest, depending on age and overall physical fitness. Here, we analyzed whether the availability and chondrogenic differentiation capacity of MSCs isolated from the femoral shaft as an alternative source is age- or OA etiology-dependent. MSCs were isolated from the bone marrow (BM) of 98 patients, categorized into three OA etiology groups (age-related, joint trauma, joint dysplasia) at the time of total hip replacement. All BM samples were characterized for cell yield, proliferation capacity, and phenotype. Chondrogenic differentiation was studied using micromass culture and analyzed by histology, immunohistochemistry, and quantitative reverse transcriptase-polymerase chain reaction. Significant volumes of viable BM (up to 25 ml) could be harvested from the femoral shaft without observing donor-site morbidity, typically containing >10(7) mononuclear cells per milliliter. No correlation of age or OA etiology with the number of mononuclear cells in BM, MSC yield, or cell size was found. Proliferative capacity and cellular spectrum of the harvested cells were independent of age and cause of OA. From all tested donors, MSCs could be differentiated into the chondrogenic lineage. We conclude that, irrespective of age and OA etiology, sufficient numbers of MSCs can be isolated and that these cells possess an adequate chondrogenic differentiation potential. Therefore, a therapeutic application of MSCs for cartilage regeneration of OA lesions seems feasible. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17872502 TI - Putative role of hyaluronan and its related genes, HAS2 and RHAMM, in human early preimplantation embryogenesis and embryonic stem cell characterization. AB - Human embryonic stem cells (hESC) promise tremendous potential as a developmental and cell therapeutic tool. The combined effort of stimulatory and inhibitory signals regulating gene expression, which drives the tissue differentiation and morphogenetic processes during early embryogenesis, is still very poorly understood. With the scarcity of availability of human embryos for research, hESC can be used as an alternative source to study the early human embryogenesis. Hyaluronan (HA), a simple hydrating sugar, is present abundantly in the female reproductive tract during fertilization, embryo growth, and implantation and plays an important role in early development of the mammalian embryo. HA and its binding protein RHAMM regulate various cellular and hydrodynamic processes from cell migration, proliferation, and signaling to regulation of gene expression, cell differentiation, morphogenesis, and metastasis via both extracellular and intracellular pathways. In this study, we show for the first time that HA synthase gene HAS2 and its binding receptor RHAMM are differentially expressed during all stages of preimplantation human embryos and hESC. RHAMM expression is significantly downregulated during differentiation of hESC, in contrast to HAS2, which is significantly upregulated. Most importantly, RHAMM knockdown results in downregulation of several pluripotency markers in hESC, induction of early extraembryonic lineages, loss of cell viability, and changes in hESC cycle. These data therefore highlight an important role for RHAMM in maintenance of hESC pluripotency, viability, and cell cycle control. Interestingly, HAS2 knockdown results in suppression of hESC differentiation without affecting hESC pluripotency. This suggests an intrinsic role for HAS2 in hESC differentiation process. In accordance with this, addition of exogenous HA to the differentiation medium enhances hESC differentiation to mesodermal and cardiac lineages. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17872503 TI - Bone morphogenetic protein signaling and olig1/2 interact to regulate the differentiation and maturation of adult oligodendrocyte precursor cells. AB - Promotion of remyelination is an important therapeutic strategy for the treatment of the demyelinating neurological disorders. Adult oligodendrocyte precursor cells (OPCs), which normally reside quiescently in the adult central nervous system (CNS), become activated and proliferative after demyelinating lesions. However, the extent of endogenous remyelination is limited because of the failure of adult OPCs to mature into myelinating oligodendrocytes (OLs) in the demyelinated CNS. Understanding the molecular mechanisms that regulate the differentiation of adult OPCs could lead to new therapeutic strategies to treat these disorders. In this study, we established a stable culture of adult spinal cord OPCs and developed a reliable in vitro protocol to induce their sequential differentiation. Adult OPCs expressed bone morphogenetic protein (BMP) type Ia, Ib, and II receptor subunits, which are required for BMP signal transduction. BMP2 and 4 promoted dose-dependent astrocyte differentiation of adult OPCs with concurrent suppression of OL differentiation. Treatment of OPCs with BMP2 and 4 increased ID4 expression and decreased the expression of olig1 and olig2. Overexpression of olig1 or olig2 blocked the astrocyte differentiation of adult OPCs induced by BMP2 and 4. Furthermore, overexpression of both olig1 and olig2, but not olig1 or olig2 alone, rescued OL differentiation from inhibition by BMP2 and 4. Our results demonstrated that downregulation of olig1 and olig2 is an important mechanism by which BMP2 and 4 inhibit OL differentiation of adult OPCs. These data suggest that blocking BMP signaling combined with olig1/2 overexpression could be a useful therapeutic strategy to enhance endogenous remyelination and facilitate functional recovery in CNS demyelinated disorders. Disclosure of potential conflicts of interest is found at the end of this article. PMID- 17872504 TI - Retraction for Shen et al: Oocyte-like cells can be differentiated from mouse embryonic stem cells induced by the stage-specific ovary-conditioned medium and cocultured ovary somatic cells in vitro. PMID- 17872505 TI - Determinants of targeting by endogenous and exogenous microRNAs and siRNAs. AB - Vertebrate mRNAs are frequently targeted for post-transcriptional repression by microRNAs (miRNAs) through mechanisms involving pairing of 3' UTR seed matches to bases at the 5' end of miRNAs. Through analysis of expression array data following miRNA or siRNA overexpression or inhibition, we found that mRNA fold change increases multiplicatively (i.e., log-additively) with seed match count and that a single 8 mer seed match mediates down-regulation comparable to two 7 mer seed matches. We identified several targeting determinants that enhance seed match-associated mRNA repression, including the presence of adenosine opposite miRNA base 1 and of adenosine or uridine opposite miRNA base 9, independent of complementarity to the siRNA/miRNA. Increased sequence conservation in the approximately 50 bases 5' and 3' of the seed match and increased AU content 3' of the seed match were each independently associated with increased mRNA down regulation. All of these determinants are enriched in the vicinity of conserved miRNA seed matches, supporting their activity in endogenous miRNA targeting. Together, our results enable improved siRNA off-target prediction, allow integrated ranking of conserved and nonconserved miRNA targets, and show that targeting by endogenous and exogenous miRNAs/siRNAs involves similar or identical determinants. PMID- 17872506 TI - Gene silencing mechanisms mediated by Aubergine piRNA complexes in Drosophila male gonad. AB - Genetic studies have shown that Aubergine (Aub), one of the Piwi subfamily of Argonautes in Drosophila, is essential for germ cell formation and maintaining fertility. aub mutations lead to the accumulation of retrotransposons in ovaries and testes, and Stellate transcripts in testes. Aub in ovaries associates with a variety of Piwi-interacting RNAs (piRNAs) derived from repetitive intergenic elements including retrotransposons. Here we found that Aub in testes also associates with various kinds of piRNAs. Although in ovaries Aub-associated piRNA populations are quite diverse, piRNAs with Aub in testes show a strong bias. The most abundant piRNAs were those corresponding to antisense transcripts of Suppressor of Stellate [Su(Ste)] genes known to be involved in Stellate gene silencing. The second most abundant class was made up of those from chromosome X and showed strong complementarity to vasa transcripts. Immunopurified Aub-piRNA complexes from testes displayed activity in cleaving target RNA containing sequences complementary to Stellate and vasa transcripts. These results provide the first biochemical insights into gene silencing mechanisms mediated by Aub and piRNAs in fly testes. PMID- 17872507 TI - RluD, a highly conserved pseudouridine synthase, modifies 50S subunits more specifically and efficiently than free 23S rRNA. AB - Pseudouridine modifications in helix 69 (H69) of 23S ribosomal RNA are highly conserved among all organisms. H69 associates with helix 44 of 16S rRNA to form bridge B2a, which plays a vital role in bridging the two ribosomal subunits and stabilizing the ribosome. The three pseudouridines in H69 were shown earlier to play an important role in 50S subunit assembly and in its association with the 30S subunit. In Escherichia coli, these three modifications are made by the pseudouridine synthase, RluD. Previous work showed that RluD is required for normal ribosomal assembly and function, and that it is the only pseudouridine synthase required for normal growth in E. coli. Here, we show that RluD is far more efficient in modifying H69 in structured 50S subunits, compared to free or synthetic 23S rRNA. Based on this observation, we suggest that pseudouridine modifications in H69 are made late in the assembly of 23S rRNA into mature 50S subunits. This is the first reported observation of a pseudouridine synthase being able to modify a highly structured ribonucleoprotein particle, and it may be an important late step in the maturation of 50S ribosomal subunits. PMID- 17872508 TI - Exoribonuclease R in Mycoplasma genitalium can carry out both RNA processing and degradative functions and is sensitive to RNA ribose methylation. AB - Mycoplasma genitalium, a small bacterium having minimal genome size, has only one identified exoribonuclease, RNase R (MgR). We have purified MgR to homogeneity, and compared its RNA degradative properties to those of its Escherichia coli homologs RNase R (EcR) and RNase II (EcII). MgR is active on a number of substrates including oligoribonucleotides, poly(A), rRNA, and precursors to tRNA. Unlike EcR, which degrades rRNA and pre-tRNA without formation of intermediate products, MgR appears sensitive to certain RNA structural features and forms specific products from these stable RNA substrates. The 3'-ends of two MgR degradation products of 23S rRNA were mapped by RT-PCR to positions 2499 and 2553, each being 1 nucleotide downstream of a 2'-O-methylation site. The sensitivity of MgR to ribose methylation is further demonstrated by the degradation patterns of 16S rRNA and a synthetic methylated oligoribonucleotide. Remarkably, MgR removes the 3'-trailer sequence from a pre-tRNA, generating product with the mature 3'-end more efficiently than EcII does. In contrast, EcR degrades this pre-tRNA without the formation of specific products. Our results suggest that MgR shares some properties of both EcR and EcII and can carry out a broad range of RNA processing and degradative functions. PMID- 17872509 TI - Substrate specificity and properties of the Escherichia coli 16S rRNA methyltransferase, RsmE. AB - The small ribosome subunit of Escherichia coli contains 10 base-methylated sites distributed in important functional regions. At present, seven enzymes responsible for methylation of eight bases are known, but most of them have not been well characterized. One of these enzymes, RsmE, was recently identified and shown to specifically methylate U1498. Here we describe the enzymatic properties and substrate specificity of RsmE. The enzyme forms dimers in solution and is most active in the presence of 10-15 mM Mg(2+) and 100 mM NH(4)Cl at pH 7-9; however, in the presence of spermidine, Mg(2+) is not required for activity. While small ribosome subunits obtained from an RsmE deletion strain can be methylated by purified RsmE, neither 70S ribosomes nor 50S subunits are active. Likewise, 16S rRNA obtained from the mutant strain, synthetic 16S rRNA, and 3' minor domain RNA are all very poor or inactive as substrates. 30S particles partially depleted of proteins by treatment with high concentrations of LiCl or in vitro reconstituted intermediate particles also show little or no methyl acceptor activity. Based on these data, we conclude that RsmE requires a highly structured ribonucleoprotein particle as a substrate for methylation, and that methylation events in the 3' minor domain of 16S rRNA probably occur late during 30S ribosome assembly. PMID- 17872510 TI - Conformational energy and structure in canonical and noncanonical forms of tRNA determined by temperature analysis of the rate of s(4)U8-C13 photocrosslinking. AB - Bacterial tRNAs frequently have 4-thiouridine (s(4)U) modification at position 8, which is adjacent to the C13-G22-m(7)G46 base triple in the elbow region of the tRNA tertiary structure. Irradiation with light in the UVA range induces an efficient photocrosslink between s(4)U8 and C13. The temperature dependence of the rate constants for photocrosslinking between the s(4)U8 and C13 has been used to investigate the tRNA conformational energy and structure in Escherichia coli tRNA(Val), tRNA(Phe), and tRNA(fMet) under different conditions. Corrections have been made in the measured rate constants to compensate for differences in the excited state lifetimes due to tRNA identity, buffer conditions, and temperature. The resulting rate constants are related to the rate at which the s(4)U8 and C13 come into the alignment needed for photoreaction; this depends on an activation energy, attributable to the conformational potential energy that occurs during the photoreaction, and on the extent of the structural change. Different photocrosslinking rate constants and temperature dependencies occur in the three tRNAs, and these differences are due both to modest differences in the activation energies and in the apparent s(4)U8-C13 geometries. Analysis of tRNA(Val) in buffers without Mg(2+) indicate a smaller activation energy (~13 kJ mol(-1)) and a larger apparent s(4)U8-C13 distance (~12 A) compared to values for the same parameters in buffers with Mg(2+) (~26 kJ mol(-1) and 0.36 A, respectively). These measurements are a quantitative indication of the strong constraint that Mg(2+) imposes on the tRNA flexibility and structure. PMID- 17872512 TI - Dicer is involved in protection against influenza A virus infection. AB - In mammals the interferon (IFN) system is a central innate antiviral defence mechanism, while the involvement of RNA interference (RNAi) in antiviral response against RNA viruses is uncertain. Here, we tested whether RNAi is involved in the antiviral response in mammalian cells. To investigate the role of RNAi in influenza A virus-infected cells in the absence of IFN, we used Vero cells that lack IFN-alpha and IFN-beta genes. Our results demonstrate that knockdown of a key RNAi component, Dicer, led to a modest increase of virus production and accelerated apoptosis of influenza A virus-infected cells. These effects were much weaker in the presence of IFN. The results also show that in both Vero cells and the IFN-producing alveolar epithelial A549 cell line influenza A virus targets Dicer at mRNA and protein levels. Thus, RNAi is involved in antiviral response, and Dicer is important for protection against influenza A virus infection. PMID- 17872511 TI - RNA-specific ribonucleotidyl transferases. AB - RNA-specific nucleotidyl transferases (rNTrs) are a diverse family of template independent polymerases that add ribonucleotides to the 3'-ends of RNA molecules. All rNTrs share a related active-site architecture first described for DNA polymerase beta and a catalytic mechanism conserved among DNA and RNA polymerases. The best known examples are the nuclear poly(A) polymerases involved in the 3'-end processing of eukaryotic messenger RNA precursors and the ubiquitous CCA-adding enzymes that complete the 3'-ends of tRNA molecules. In recent years, a growing number of new enzymes have been added to the list that now includes the "noncanonical" poly(A) polymerases involved in RNA quality control or in the readenylation of dormant messenger RNAs in the cytoplasm. Other members of the group are terminal uridylyl transferases adding single or multiple UMP residues in RNA-editing reactions or upon the maturation of small RNAs and poly(U) polymerases, the substrates of which are still not known. 2'-5'Oligo(A) synthetases differ from the other rNTrs by synthesizing oligonucleotides with 2' 5'-phosphodiester bonds de novo. PMID- 17872513 TI - Comparison of the antiviral potentials among the pseudorabies-resistant transgenes encoding different soluble forms of porcine nectin-1 in transgenic mice. AB - Nectin-1 is an alphaherpesvirus receptor that binds to virion glycoprotein D by the first immunoglobulin (Ig)-like domain. The possibility of making animals resistant to pseudorabies virus (PRV) infection has been investigated by generating transgenic mice expressing soluble forms of porcine nectin-1. Previously, transgenic mice were generated that expressed a fusion protein made of the entire ectodomain of nectin-1 fused to the Fc portion of human IgG, or the first Ig-like domain fused to the Fc portion of porcine IgG. Here, the contribution of the second and third Ig-like domains of nectin-1 was analysed by generating transgenic mice expressing the entire ectodomain of nectin-1 fused to the porcine Fc portion. Transgenic mice expressing each of three different fusion proteins were challenged with PRV for comparison of their resistance. Altogether, mice transgenic for a chimera that carried the entire ectodomain were more resistant than those transgenic for a chimera that carried the first Ig-like domain. PMID- 17872514 TI - Cytomegaloviral proteins pUL50 and pUL53 are associated with the nuclear lamina and interact with cellular protein kinase C. AB - Human cytomegalovirus-encoded pUL50 and pUL53 belong to a group of conserved herpesviral nuclear proteins. This study describes: (i) the co-localization of pUL50 with components of the nuclear lamina such as lamins A/C and lamin B receptor by double immunofluorescent staining, (ii) a strong pUL50-mediated relocalization of pUL53 from a diffuse nuclear pattern towards a nuclear rim localization, (iii) a direct interaction between pUL50 and pUL53, as well as between pUL50 and protein kinase C (PKC), shown by yeast two-hybrid and co immunoprecipitation analyses, (iv) in vitro phosphorylation of pUL50, which is highly suggestive of PKC activity, and finally (v) partial relocalization of PKC by pUL50/pUL53 from its main cytoplasmic localization to a marked nuclear lamina accumulation. These data suggest a role for pUL50 and pUL53 in the recruitment of PKC, an event that is considered to be important for cytomegalovirus-induced distortion of the nuclear lamina. PMID- 17872515 TI - Discovery of herpesviruses in bats. AB - Seven novel gammaherpesviruses (GHV) and one novel betaherpesvirus were discovered in seven different European bat species (order Chiroptera, family Vespertilionidae) with a pan-herpesvirus PCR assay, targeting the DNA polymerase (DPOL) gene. The sequences of six bat GHV were similarly related to members of the gammaherpesvirus genera Percavirus and Rhadinovirus. The seventh GHV was related to the porcine lymphotropic herpesvirus 1 (genus Macavirus). The betaherpesvirus appeared to be a distant relative of human cytomegalovirus. For three bat GHV a 3.6 kbp locus was amplified and sequenced, spanning part of the glycoprotein B gene and the majority of the DPOL gene. In phylogenetic analysis, the three bat GHV formed a separate clade with similar distance to the Percavirus and Rhadinovirus clades. These novel viruses are the first herpesviruses to be described in bats. PMID- 17872516 TI - Post-translational modifications of Epstein Barr virus BARF1 oncogene-encoded polypeptide. AB - Epstein-Barr virus is associated with several human lymphomas and carcinomas, and its BARF1 oncogene encodes a protein that is thought to play an important role in carcinogenesis. A BARF1 recombinant adenovirus expression system, which led us to discover the macromolecular size of the cleaved and secreted form of the BARF1 protein in the native state and its mitogenic capacity on various cell lines in culture, was used further to investigate the structure and maturation of the BARF1 protein. We recently reported biophysical studies that showed dimer-based oligomerization of the BARF1 polypeptide. Here, new data are presented that confirm post-translational modifications predicted from the BARF1 sequence: phosphorylation on serine and threonine, and N- and O-glycosylation. The N- and O glycans were partially characterized and it was demonstrated that both modifications are required for active secretion of the BARF1 protein via the classical pathway. PMID- 17872517 TI - Genetic diversity of cutaneous human papillomaviruses. AB - Human papillomaviruses (HPVs) of the genera Betapapillomavirus and Gammapapillomavirus are common on human skin. Sequencing of subgenomic amplicons of cutaneous HPVs has revealed a large number of novel putative HPV types within these genera. Phylogenetic analysis based on these amplicons revealed 133 putative HPV types with <90 % sequence identity to any known HPV type or to each other. As there are already 34 characterized HPV types described within the genera Betapapillomavirus and Gammapapillomavirus, they appear to be the most genetically diverse of the HPVs, apparently comprising at least 167 different HPV types. PMID- 17872518 TI - Persistence of Mastomys natalensis papillomavirus in multiple organs identifies novel targets for infection. AB - The high incidence of multiple wart formation and skin cancer in organ-transplant recipients, as well as the question of an involvement of papillomaviruses in a variety of human cancers, require a model system for papillomavirus infections in immunocompetent animals. Such an in vivo model is represented by the multimammate rat Mastomys coucha, which is infected with Mastomys natalensis papillomavirus (MnPV). MnPV primarily induces benign skin tumours, such as papillomas and keratoacanthomas. Here, the incidence of MnPV infections in different skin areas and various organs is described. In situ hybridization showed that hair follicle cells were positive for viral DNA and that the amount of MnPV in normal skin may be considered a predictor for the development of skin tumours. MnPV infection is not restricted to the skin, but can also be detected in inner organs. As the blood and the lymphatic system were temporarily also found to be virus-positive, a haematogenic propagation of MnPV can be assumed. However, MnPV is apparently not transmitted through the germ line, as fetuses and newborns lack viral DNA, despite infection of their mothers. In conclusion, M. coucha is not only useful to study papillomavirus-induced skin carcinogenesis, but may also serve as a model to identify additional, still unknown target cells of papillomavirus infections and the potential pathological impact. PMID- 17872519 TI - Complete-genome analysis of hepatitis B virus from wild-born chimpanzees in central Africa demonstrates a strain-specific geographical cluster. AB - In order to determine whether geographical or species clustering accounts for the distribution of hepatitis B virus (HBV) in subspecies of chimpanzees in Africa, four complete chimpanzee HBV (ChHBV) genome sequences were obtained from eight hepatitis B surface antigen-positive wild-born chimpanzees from Cameroon, Republic of Congo and Gabon. The serological profiles of these chimpanzees corresponded to the acute or chronic highly replicative phase of HBV infection, as confirmed by high plasma HBV loads. Analysis of the sequence alignment of 256 aa (S region) from the eight HBV-infected chimpanzees allowed us to determine the HBV amino acid patterns specific to each chimpanzee subspecies and to their geographical origin. Phylogenetic analysis of both the S region and the complete genome confirmed this distinctive clustering of eight novel ChHBV strains within Pan troglodytes. The strong phylogenetic associations of ChHBV sequences with both chimpanzee subspecies and their geographical origin were therefore confirmed. PMID- 17872520 TI - Maternofetal transmission of hepatitis B virus genotype E in Ghana, west Africa. AB - To determine whether maternofetal transmission of hepatitis B virus (HBV) is a common route of infection leading to chronic infection in west Africa, plasma samples, obtained at delivery from 1368 pregnant Ghanaian women and paired umbilical cord blood or newborn whole blood samples, were tested for HBV surface antigen (HBsAg) and DNA. A 16 % prevalence of HBV chronic carriers, defined as detectable HBsAg and/or HBV DNA, was found, >80 % contained less than 1 x 10(4) IU ml(-1) HBV DNA and 99 % were infected with genotype E strains. HBV maternofetal transmission was documented in 17 out of 204 (8.3 %) paired HBV carrier women-cord blood/newborn samples. The rate of transmission was 55 % and 3.3 % when maternal viral load was above or below 1 x 10(4) IU ml(-1), respectively (P=0.0008). Maternofetal transmission of HBV genotype E was estimated to account for 8 % of the cases of chronic HBsAg carriers. Six women with low viral load at delivery (five <20 IU ml(-1)) and anti-HBe (hepatitis B e antigen) transmitted HBV. Surprisingly, while non-transmitted low viral load strains had 79 % mutations at position 1896 of HBV genome, transmitted strains were all wild-type despite anti-HBe presence (P=0.0041), suggesting the possible role of HBeAg as risk factor for HBV maternofetal transmission. The relative risk of maternofetal transmission was 2.4 when pregnant women carried high viral load and 11.5 when carrying wild-type strains at position 1896, irrespective of viral load. We conclude that viral load and pre-core wild-type at position 1896 are two independent risk factors for HBV genotype E maternofetal transmission, which remains a minor contributor to high prevalence of chronic infection. PMID- 17872521 TI - Circular genomes related to anelloviruses identified in human and animal samples by using a combined rolling-circle amplification/sequence-independent single primer amplification approach. AB - A combined rolling-circle amplification (RCA) and sequence-independent single primer amplification (SISPA) approach was applied to four samples of human plasma and one sample of saliva from a cat. This approach permitted the characterization of nine anelloviruses. Most of them were identified as highly divergent strains that were classified into species of the genus Anellovirus. The smallest anellovirus described so far in humans was characterized (2PoSMA, 2002 nt; 'small anellovirus' species). Two highly divergent sequences belonging to the species Torque Teno Mini Virus (LIL-y1, 2887 nt; LIL-y2, 2871 nt), which clustered into a new phylogenetic branch, were also identified in human plasma samples. Finally, two genomes that are separated by a genetic divergence of 46 % were characterized in the cat's saliva, one of these creating a distinct phylogenetic branch (PRA1, 2019 nt). These results highlight the potential of RCA-SISPA for detecting circular (or circularized) genomes. PMID- 17872522 TI - Immunization of Syrian golden hamsters with F subunit vaccine of human metapneumovirus induces protection against challenge with homologous or heterologous strains. AB - Human metapneumovirus (hMPV), a newly discovered paramyxovirus, is associated with acute respiratory-tract illness, primarily in young children, individuals with underlying disease and the elderly. Two genetic lineages of hMPV circulate around the world, and viruses from these two lineages demonstrate antigenic differences. The clinical impact of hMPV warrants the development of vaccines. Recombinant soluble fusion (F) proteins of prototype viruses of the two main lineages of hMPV that can be produced in high yields have been constructed. In this study, the antigenicity, immunogenicity and protective efficacy of these soluble F subunit vaccines were evaluated in Syrian golden hamsters (Mesocricetus auratus). Immunization of hamsters with the soluble F proteins, adjuvanted with Specol or iscom matrix, induced high virus-neutralization titres, with higher titres against the homologous than the heterologous virus. The neutralizing antibodies protected from subsequent infection of the lungs with both homologous and heterologous virus. Upon challenge, viral titres in the nasal turbinates of immunized animals were reduced significantly compared with those of PBS-immunized animals. In conclusion, a soluble F subunit vaccine for hMPV that induces cross protective immunity for infection of the lower respiratory tract in Syrian golden hamsters has been generated. PMID- 17872523 TI - Measles virus minigenomes encoding two autofluorescent proteins reveal cell-to cell variation in reporter expression dependent on viral sequences between the transcription units. AB - Transcription from morbillivirus genomes commences at a single promoter in the 3' non-coding terminus, with the six genes being transcribed sequentially. The 3' and 5' untranslated regions (UTRs) of the genes (mRNA sense), together with the intergenic trinucleotide spacer, comprise the non-coding sequences (NCS) of the virus and contain the conserved gene end and gene start signals, respectively. Bicistronic minigenomes containing transcription units (TUs) encoding autofluorescent reporter proteins separated by measles virus (MV) NCS were used to give a direct estimation of gene expression in single, living cells by assessing the relative amounts of each fluorescent protein in each cell. Initially, five minigenomes containing each of the MV NCS were generated. Assays were developed to determine the amount of each fluorescent protein in cells at both cell population and single-cell levels. This revealed significant variations in gene expression between cells expressing the same NCS-containing minigenome. The minigenome containing the M/F NCS produced significantly lower amounts of fluorescent protein from the second TU (TU2), compared with the other minigenomes. A minigenome with a truncated F 5' UTR had increased expression from TU2. This UTR is 524 nt longer than the other MV 5' UTRs. Insertions into the 5' UTR of the enhanced green fluorescent protein gene in the minigenome containing the N/P NCS showed that specific sequences, rather than just the additional length of F 5' UTR, govern this decreased expression from TU2. PMID- 17872524 TI - Characterization of the epitope for anti-human respiratory syncytial virus F protein monoclonal antibody 101F using synthetic peptides and genetic approaches. AB - Chimeric 101F (ch101F) is a mouse-human chimeric anti-human respiratory syncytial virus (HRSV) neutralizing antibody that recognizes residues within antigenic site IV, V, VI of the fusion (F) glycoprotein. The binding of ch101F to a series of peptides overlapping aa 422-438 spanning antigenic site IV, V, VI was analysed. Residues 423-436 comprise the minimal peptide sequence for ch101F binding. Substitution analysis revealed that R429 and K433 are critical for ch101F binding, whilst K427 makes a minor contribution. Binding of ch101F to a series of single mutations at positions 427, 429 and 433 in the F protein expressed recombinantly on the cell surface confirmed the peptide results. Sequence analysis of viruses selected for resistance to neutralization by ch101F indicated that a single change (K433T) in the F protein allowed ch101F escape. The results confirm that ch101F and palivizumab have different epitope specificity and define key residues for ch101F recognition. PMID- 17872525 TI - Molecular mechanisms of reversion to the ts+ (non-temperature-sensitive) phenotype of influenza A cold-adapted (ca) virus strains. AB - A ts+ ca- (non-temperature-sensitive, non-cold-adapted) revertant of the A/Leningrad/134/47/57 ca strain influenza virus [A/Leningrad/134/47/ts+18/1957(H2N2)], obtained in our previous study, lost phenotypic manifestation of ts mutations by the PB2, NP and NS genes, although, according to sequencing data, it acquired only two true reversions of a mutation in the PB2 and PB1 genes. Direct sequencing showed the appearance of 27 additional mutations (13 coding) in the genes encoding the PB2, PB1, PA, NP, M and NS proteins of the revertant, along with the above-mentioned two true reversions. We conjecture that some of these mutations suppressed phenotypic manifestation of ts mutations in the NS and NP genes. PMID- 17872526 TI - Superinfection exclusion in BHK-21 cells persistently infected with Junin virus. AB - We characterized a persistently Junin virus (JUNV)-infected BHK-21 cell line obtained by experimental infection with the XJCl3 strain. This cell line, named K3, produced low levels of virus in supernatants which were not influenced by the presence of defective interfering (DI) particles after the first year of infection. K3 cells were able to exclude superinfection of the homologous JUNV and the antigenically related Tacaribe virus (TCRV), whereas the non-related arenaviruses lymphocytic choriomeningitis virus (LCMV) and Pichinde virus (PICV) could replicate normally. Although superinfecting virus binding and internalization to persistently infected cells were slightly reduced, earlier biosynthesis of antigenomic RNA was observed in comparison with BHK-21 cells. Despite the fact that superinfection did not increase the number of cells expressing viral antigens, de novo synthesis of superinfecting virus proteins was detected. The virus produced by JUNV-superinfected K3 cells remained mostly cell associated in the form of particles tethered to the plasma membrane and aberrant tubular structures. JUNV restriction was correlated with an overexpression of cellular protein TSG101 in K3 cells, which has been pointed out as involved in the budding of several RNA viruses. This correlation was also observed in a cell clone isolated from K3. Reduction of TSG101 expression favoured the release of infectious virus to the supernatant of JUNV-superinfected K3 cells. Our data suggest that overexpression of TSG101 in K3 cells is a novel mechanism that may contribute, along with a diminished synthesis of superinfecting virus proteins, to explain superinfection exclusion in persistently arenavirus-infected cells. PMID- 17872527 TI - Persistent memory CD4+ and CD8+ T-cell responses in recovered severe acute respiratory syndrome (SARS) patients to SARS coronavirus M antigen. AB - The membrane (M) protein of severe acute respiratory syndrome coronavirus (SARS CoV) is a major glycoprotein with multiple biological functions. In this study, we found that memory T cells against M protein were persistent in recovered SARS patients by detecting gamma interferon (IFN-gamma) production using ELISA and ELISpot assays. Flow cytometric analysis showed that both CD4+ and CD8+ T cells were involved in cellular responses to SARS-CoV M antigen. Furthermore, memory CD8+ T cells displayed an effector memory cell phenotype expressing CD45RO- CCR7- CD62L-. In contrast, the majority of IFN-gamma+ CD4+ T cells were central memory cells with the expression of CD45RO+ CCR7+ CD62L-. The epitope screening from 30 synthetic overlapping peptides that cover the entire SARS-CoV M protein identified four human T-cell immunodominant peptides, p21-44, p65-91, p117-140 and p200-220. All four immunodominant peptides could elicit cellular immunity with a predominance of CD8+ T-cell response. This data may have important implication for developing SARS vaccines. PMID- 17872528 TI - Comparative analysis of innate immune responses following infection of newborn calves with bovine rotavirus and bovine coronavirus. AB - Bovine rotavirus (BRV) and bovine coronavirus (BCV) are important causes of diarrhoea and death in newborn calves. Although these viruses belong to distinct viral classes, they both infect intestinal epithelial cells and induce similar clinical symptoms. Rotavirus usually causes an acute infection, but coronavirus infection can persist and reoccur in adults. Differences in viral structure and clinical outcome prompted us to postulate that innate mucosal immune responses would be markedly different following rotavirus and coronavirus infections. To address this hypothesis, gene expression following BRV and BCV infection was analysed in surgically prepared intestinal loops from 1-day-old colostrum deprived calves. Gene expression was profiled at 18 h post-infection using bovine cDNA microarrays; the majority of differentially expressed significant genes were associated with the cell cycle and innate immune responses. A select group of these genes was validated by quantitative real-time PCR (qRT-PCR). The expression of genes associated with interferons (IFNs), cytokines and Toll-like receptors, which were not present on the microarray, was analysed further by qRT-PCR. Strong activation of TLR3, IL-6 and p65 was observed in BRV-infected host tissues, but not in tissues infected with BCV. Both viruses also downregulated IFN- and pro inflammatory cytokine-associated pathways. In vitro studies confirmed that IFN inhibited viral replication. All of these results together suggested either that very early events of host responses at 18 h post-infection were being observed, or that both viruses have unique effective strategies to evade host immune responses. PMID- 17872529 TI - Molecular epidemiological analyses of Japanese encephalitis virus isolates from swine in Japan from 2002 to 2004. AB - To characterize Japanese encephalitis virus (JEV) strains recently prevalent in Japan, JEV surveillance was performed in pigs from 2002 to 2004. Eleven new JEV isolates were obtained and compared with previous isolates from Japan and other Asian countries. All of the isolates were classified into genotype 1 by nucleotide sequence analysis of the E gene. Two new isolates with different levels of neurovirulence and neuroinvasiveness, but with only one nucleotide difference in the E gene, Sw/Mie/34/2004 and Sw/Mie/40/2004, were isolated at the same farm on the same day. Sw/Mie/40/2004 displayed higher neurovirulence and neuroinvasiveness in mice than the other four new isolates. Another new isolate, Sw/Hiroshima/25/2002, was neutralized by antiserum to Beijing-1 at a level similar to the homologous Beijing-1 strain, whilst seven other new isolates were neutralized at 10-fold-lower titres. However, there were no amino acid differences in the E protein among these eight isolates. The present study indicated that the 11 new JEV isolates were genetically similar, but biologically and serologically heterogeneous. PMID- 17872530 TI - Rubella virus-induced superinfection exclusion studied in cells with persisting replicons. AB - For the first time, homologous superinfection exclusion was documented for rubella virus (RUB) by using Vero cells harbouring persisting RUB replicons. Infection with wild-type RUB was reduced by tenfold, whereas Sindbis virus infection was unaffected. Replication following infection with packaged replicons and transfection with replicon transcripts was also restricted in these cells, indicating that restriction occurred after penetration and entry. Translation of such 'supertransfecting' replicon transcripts was not impaired, but no accumulation of supertransfecting replicon RNA could be detected. We tested the hypothesis favoured in the related alphaviruses that superinfection exclusion is mediated by cleavage of the incoming non-structural precursor by the pre-existing non-structural (NS) protease, resulting in an inhibition of minus-strand RNA synthesis. However, cleavage of a precursor translated from a supertransfecting replicon transcript with an NS protease catalytic-site mutation was not detected and the event in the replication cycle at which superinfection exclusion is executed remains to be elucidated. PMID- 17872531 TI - Increased human immunodeficiency virus type 1 Env expression and antibody induction using an enhanced alphavirus vector. AB - Viral vectors encoding heterologous vaccine antigens are potent inducers of cellular immune responses, but they are generally less efficient at stimulating humoral immunity. To improve the induction of antibody responses by Semliki Forest virus-based vaccines, a vector encoding a translation-enhancer element and a novel internal signal sequence for increased expression and secretion of soluble antigens was designed. Approximately tenfold more human immunodeficiency virus type 1 gp120 was secreted into culture supernatants of infected cells using the enhanced vector compared with the parental vector. This translated into a significant increase in gp120-specific antibodies in immunized mice, suggesting that antigen-expression levels from the parental vector are limiting for induction of antibody responses. These data encourage the use of the enhanced vector for elicitation of immune responses against heterologous antigens during vaccination. PMID- 17872532 TI - Effects of vpu start-codon mutations on human immunodeficiency virus type 1 replication in macrophages. AB - The human immunodeficiency virus type 1 (HIV-1) vpu protein increases the release of virus particles from infected cells. Mutations that abrogate vpu function have a profound effect on HIV-1 replication in primary macrophage cultures. About 1.24 % of primary isolates in the HIV databases have vpu start-codon mutations. In addition, the envelope of the AD8 isolate was reported to compensate for the lack of vpu, whilst the YU-2 virus (cloned directly from the brain tissue of an infected individual) is macrophage-tropic, despite having a vpu start-codon mutation. These observations raise the possibility that envelopes evolve to compensate for the loss of vpu function in vivo. Chimeric vpu+ and vpu- replication-competent clones were constructed that contained the envelopes of SF162, AD8 or YU-2. Macrophages were infected with these chimeras and virus release was measured over time by a reverse transcriptase ELISA. It was found that vpu-deficient chimeras carrying AD8 and YU-2 envelopes were consistently released at lower levels than their wild-type (wt) vpu counterparts, indicating that these envelopes did not compensate for the lack of vpu. Non-chimeric vpu+ and vpu- AD8 and YU-2 followed similar patterns, although replication by vpu deficient AD8 was variable, with virion release reaching 60 % of that recorded for AD8 with a wt vpu. In summary, no evidence was found that the AD8 or YU-2 envelopes can compensate for the lack of vpu for replication in macrophages. PMID- 17872533 TI - A feline immunodeficiency virus vif-deletion mutant remains attenuated upon infection of newborn kittens. AB - This report characterizes lentivirus attenuation associated with a vif mutation by inoculation of newborn kittens with a vif-deleted feline immunodeficiency virus provirus plasmid (FIV-pPPRDeltavif). Virus in peripheral blood, antiviral antibody or CD4 T-cell count alterations were not detected in kittens inoculated with FIV-pPPRDeltavif plasmid, with the exception of one kitten that demonstrated FIV Gag antibody production at 42 weeks after inoculation. In contrast, wild-type FIV-pPPR-infected kittens were viraemic, seropositive and exhibited a decrease in the CD4 T-cell subset in peripheral blood. Interestingly, FIV-specific T-cell proliferative responses detected at 32 and 36 weeks after infection were comparable for both FIV-pPPRDeltavif- and wild-type FIV-pPPR-inoculated kittens and suggested the possibility of a discreet tissue reservoir supporting sustained FIV-pPPRDeltavif expression or replication. Overall, these findings confirmed that the severe virus attenuation for both replication and pathogenicity exhibited by a vif-deleted FIV mutant is similar for both neonatal and adult hosts. PMID- 17872534 TI - Impaired hyperphosphorylation of rotavirus NSP5 in cells depleted of casein kinase 1alpha is associated with the formation of viroplasms with altered morphology and a moderate decrease in virus replication. AB - The rotavirus (RV) non-structural protein 5, NSP5, is encoded by the smallest of the 11 genomic segments and localizes in 'viroplasms', cytoplasmic inclusion bodies in which viral RNA replication and packaging take place. NSP5 is essential for the replicative cycle of the virus because, in its absence, viroplasms are not formed and viral RNA replication and transcription do not occur. NSP5 is produced early in infection and undergoes a complex hyperphosphorylation process, leading to the formation of proteins differing in electrophoretic mobility. The role of hyperphosphorylation of NSP5 in the replicative cycle of rotavirus is unknown. Previous in vitro studies have suggested that the cellular kinase CK1alpha is responsible for the NSP5 hyperphosphorylation process. Here it is shown, by means of specific RNA interference, that in vivo, CK1alpha is the enzyme that initiates phosphorylation of NSP5. Lack of NSP5 hyperphosphorylation affected neither its interaction with the virus VP1 and NSP2 proteins normally found in viroplasms, nor the production of viral proteins. In contrast, the morphology of viroplasms was altered markedly in cells in which CK1alpha was depleted and a moderate decrease in the production of double-stranded RNA and infectious virus was observed. These data show that CK1alpha is the kinase that phosphorylates NSP5 in virus-infected cells and contribute to further understanding of the role of NSP5 in RV infection. PMID- 17872535 TI - Design of primers and use of RT-PCR assays for typing European bluetongue virus isolates: differentiation of field and vaccine strains. AB - Bluetongue virus (BTV) is the causative agent of bluetongue, a disease of ruminant livestock that occurs almost worldwide between latitudes 3 degrees S and 5 degrees N. There are 24 serotypes of BTV (currently identified by serum neutralization assays). Since 1998, eight strains of six BTV serotypes (1, 2, 4, 8, 9 and 16) have invaded Europe. The most variable BTV protein is major outer capsid component VP2, encoded by segment 2 (Seg-2) of the double-stranded RNA virus genome. VP2 represents the major target for neutralizing (and protective) antibodies that are generated in response to BTV infection, and is therefore the primary determinant of virus serotype. RT-PCR primers and assays targeting Seg-2 have been developed for rapid identification (within 24 h) of the six European BTV types. These assays are sensitive, specific and show perfect agreement with the results of conventional virus-neutralization methods. Previous studies have identified sequence variations in individual BTV genome segments that allow different isolates to be grouped on the basis of their geographical origins (topotypes). The assays described in this paper can detect any of the BTV isolates of the homologous serotype that were tested from different geographical origins (different Seg-2 topotypes). Primers were also identified that could be used to distinguish members of these different Seg-2 topotypes, as well as field and vaccine strains of most of the European BTV serotypes. The serotype-specific assays (and primers) showed no cross-amplification when they were evaluated with multiple isolates of the most closely related BTV types or with reference strains of the remaining 24 serotypes. Primers developed in this study will be updated periodically to maintain their relevance to current BTV distribution and epidemiology (http://www.iah.bbsrc.ac.uk/dsRNA_virus_proteins/ReoID/rt-pcr primers.htm). PMID- 17872536 TI - Evidence for functional significance of the permuted C motif in Co2+-stimulated RNA-dependent RNA polymerase of infectious bursal disease virus. AB - Segment B of bisegmented infectious bursal disease virus (IBDV) encodes virus protein 1 (VP1), possessing RNA-dependent RNA polymerase (RdRp) activity. This multidomain protein includes an RdRp domain with a non-canonical order of three sequence motifs forming the active site: C-A-B. The A-B-C order of the motifs, as found in RdRps of the majority of viruses, was converted by relocation (permutation) of motif C to a C-A-B order. Due to the unusual location and unproven significance, the motif was named 'C?'. This motif includes an Ala-Asp Asn tripeptide that replaces the C motif Gly-Asp-Asp sequence, widely considered a hallmark of RdRps. In this study, functional significance of the C? motif was investigated by using purified His-tagged VP1 mutants with either a double replacement (ADN to GDD) or two single-site mutants (ADD or GDN). All mutants showed a significant reduction of RdRp activity in vitro, in comparison to that of VP1. Only the least-affected GDN mutant gave rise to viable, albeit partially impaired, progeny using a reverse-genetics system. Experiments performed to investigate whether the C motif was implicated in the control of metal dependence revealed that, compared with Mn2+ and Mg2+, Co2+ stimulated RdRp unconventionally. No activity was observed in the presence of several divalent cations. Of two Co2+ salts with Cl- and SO4(2-) anions, the former was a stronger stimulant for RdRp. When cell-culture medium was supplemented with 50 microM Co2+, an increase in IBDV progeny yield was observed. The obtained results provide evidence that the unusual Co2+ dependence of the IBDV RdRp might be linked to the permuted organization of the motif. PMID- 17872537 TI - Ectropis obliqua picorna-like virus IRES-driven internal initiation of translation in cell systems derived from different origins. AB - Ectropis obliqua picorna-like virus (EoPV) is an insect RNA virus that causes a lethal granulosis infection of larvae of the tea looper (Ectropis obliqua). An internal ribosome entry site (IRES) mediates translation initiation of EoPV RNA. Here, bicistronic constructs were used to examine the 5' untranslated region (UTR) of EoPV for IRES activity. The capacities of the EoPV 5' UTR IRES and another insect virus IRES, the cricket paralysis virus intergenic region IRES, to mediate internal translation initiation in a variety of translation systems were also compared. The results demonstrated that the EoPV IRES functioned efficiently not only in mammalian cell-derived systems, but also in an insect cell-derived translation system. However, it functioned inefficiently in a plant cell-derived translation system. This study reveals the host preferences of the EoPV IRES and important differences in IRES function between the EoPV IRES and other characterized picorna-like insect viral IRESs. PMID- 17872538 TI - Adaptation of plum pox virus to a herbaceous host (Pisum sativum) following serial passages. AB - Plum pox virus (PPV) populations from peaches are able to adapt consistently to herbaceous hosts, characterized by a reduction in time to symptom development, increases in inoculation efficiency and increased titres. PPV adaptation was studied by using pea (Pisum sativum) as an alternative host. Two isolates of PPV from peaches were inoculated and passaged in peas ten times using either aphid or mechanical inoculation, generating four independent passage lines. Mechanical transmission efficiency from peach to pea improved from 3 % at passage 1 to 100 % by serial passage 4 on peas. Inoculation using aphid vectors required six to ten serial passages in pea to reach a peak of 50-60 % transmission efficiency. Sequence analyses of all four PPV population lines inoculated sequentially to pea identified a specific mutation occurring consistently in the NIb gene when compared with the same PPV isolates passaged in parallel in peach. The mutation allowed PPV to replicate up to 20 times faster in the new host. Pea-adapted strains of PPV at every passage were also tested for their ability to infect the original host, peach. Regardless of the number of previous passages, all pea adapted PPV strains consistently infected peach at low levels using aphid inoculation. PMID- 17872539 TI - A chimeric plum pox virus shows reduced spread and cannot compete with its parental wild-type viruses in a mixed infection. AB - The effect of a recombination event in the genomic 3' end on the biological properties and competitiveness of plum pox virus (PPV) was investigated. Therefore, a fragment spanning the coat protein (CP) coding region and a part of the 3' non-translated region of a non-aphid-transmissible strain of PPV (PPV-NAT) was replaced by the corresponding region of a PPV sour cherry isolate (PPV-SoC). The resulting chimera (PPV-NAT/SoC) caused severe symptoms in Nicotiana benthamiana, resembling those of PPV-NAT. In mixed infections with either of the parental viruses, the chimera PPV-NAT/SoC was less competitive. Labelling experiments with DsRed showed that PPV-NAT/SoC (PPV-NAT/SoC-red) moved more slowly from cell to cell than PPV-NAT (PPV-NAT-red). In mixed infections of PPV NAT/SoC-red with a green fluorescent protein-expressing PPV-NAT (PPV-NAT-AgfpS), spatial separation of the viruses was observed. These data suggest that, in PPV infections, symptom severity and competitiveness are independent aspects and that spatial separation may contribute to the displacement of a recombinant virus. PMID- 17872540 TI - Biological properties and relative fitness of inter-subgroup cucumber mosaic virus RNA 3 recombinants produced in vitro. AB - In vitro reverse transcription of a mixture of total RNA from plants infected with the I17F or R strains of cucumber mosaic virus (CMV), representative of subgroups IA and II, respectively, results in viral cDNA populations including rare recombinant RNA 3 molecules, some of which also have point mutations. The biological properties of 17 recombinants in the capsid gene or the 3' non-coding region of RNA 3 were evaluated when associated with I17F RNAs 1 and 2. Six viruses displayed deficiencies (non-viability, deficiencies for movement and/or replication, delayed infection, loss of aphid transmissibility). Nine induced symptoms close to those of I17F-CMV on tobacco and pepper plants. All recombinants bearing the movement protein (MP) of R-CMV and part or most of the capsid protein (CP) of I17F-CMV, as well as the recombinant created in vitro by exchanging the corresponding open reading frames, also induced filiformism on tobacco, but induced only faint symptoms on melon. Two recombinants induced atypically severe symptoms on both tobacco and pepper. Most of the recombinants generally accumulated to lower levels than the wild-type I17F strain in tobacco. Three recombinants, however, including one responsible for severe symptoms, accumulated to generally higher levels than I17F-CMV. When two of these were tested in co-infection experiments with I17F RNA 3, they proved to be poorly competitive, suggesting that they would be unlikely to emerge in the field. PMID- 17872541 TI - A cucumber mosaic virus mutant lacking the 2b counter-defence protein gene provides protection against wild-type strains. AB - Several plant virus mutants, in which genes encoding silencing suppressor proteins have been deleted, are known to induce systemic or localized RNA silencing against themselves and other RNA molecules containing homologous sequences. Thus, it is thought that many cases of cross-protection, in which infection with a mild or asymptomatic virus mutant protects plants against challenge infection with closely related virulent viruses, can be explained by RNA silencing. We found that a cucumber mosaic virus (CMV) mutant of the subgroup IA strain Fny (Fny-CMVDelta2b), which cannot express the 2b silencing suppressor protein, cross-protects tobacco (Nicotiana tabacum) and Nicotiana benthamiana plants against disease induction by wild-type Fny-CMV. However, protection is most effective only if inoculation with Fny-CMVDelta2b and challenge inoculation with wild-type CMV occurs on the same leaf. Unexpectedly, Fny-CMVDelta2b also protected plants against infection with TC-CMV, a subgroup II strain that is not closely related to Fny-CMV. Additionally, in situ hybridization revealed that Fny CMVDelta2b and Fny-CMV can co-exist in the same tissues but these tissues contain zones of Fny-CMVDelta2b-infected host cells from which Fny-CMV appears to be excluded. Taken together, it appears unlikely that cross-protection by Fny CMVDelta2b occurs by induction of systemic RNA silencing against itself and homologous RNA sequences in wild-type CMV. It is more likely that protection occurs through either induction of very highly localized RNA silencing, or by competition between strains for host cells or resources. PMID- 17872542 TI - Electron-lucent inclusion bodies are structures specialized for aphid transmission of cauliflower mosaic virus. AB - Cauliflower mosaic virus (CaMV) is transmitted by aphids. For acquisition by the vector, a transmissible complex must form, composed of the virus particle, the viral coat-associated protein P3 and the helper protein P2. However, the components of the transmissible complex are largely separated in infected plant cells: most P3 virions are confined in electron-dense inclusion bodies, whereas P2 is sequestered in electron-lucent inclusion bodies (elIBs). This spatial separation controls virus acquisition by favouring the binding of virus-free P2 to the vector first, rendering the vector competent for later uptake of P3 virions. Consequently, sequential acquisition of virus from different cells or tissues is possible, with important implications for the biology of CaMV transmission. CaMV strains Campbell and CM1841 contain a single amino acid mutation (G94R) in the helper protein P2, rendering them non-transmissible from plant to plant. However, the mutant P2-94 protein supports aphid transmission when expressed heterologously and supplied to P3-CaMV complexes in vitro. The non transmissibility of P2-94 was re-examined in vivo and it is shown here that the non-transmissibility of this P2 mutant is not due to low accumulation levels in infected plants, as suggested previously, but more specifically to the failure to form elIBs within infected plant cells. This demonstrates that elIBs are complex viral structures specialized for aphid transmission and suggests that viral inclusion bodies other than viral factories, most often considered as 'garbage cans', can in fact exhibit specific functions. PMID- 17872543 TI - A monopartite begomovirus-associated DNA beta satellite substitutes for the DNA B of a bipartite begomovirus to permit systemic infection. AB - DNA beta is a circular single-stranded satellite DNA which co-infects with certain monopartite helper begomoviruses to cause economically important diseases, such as cotton leaf curl disease (CLCuD). DNA beta encodes a single protein, betaC1. Tomato leaf curl New Delhi virus (ToLCNDV) is a bipartite begomovirus in which both DNA A and DNA B are required for systemic infection. Inoculation of tomato plants with ToLCNDV DNA A alone induced local but not systemic infection, whereas co-inoculation with DNA A and the DNA beta associated with CLCuD resulted in systemic infection. DNA beta containing a disrupted betaC1 open reading frame (ORF) did not mobilize DNA A systemically. Co-inoculation of plants with DNA A and a construct of the betaC1 ORF, under the control of the cauliflower mosaic virus 35S promoter, resulted in the systemic movement of DNA A. In inoculated tobacco and onion epidermal cells, betaC1 fused to GFP was localized at the cell periphery in association with punctate bodies, around and within the cell nucleus and with the endoplasmic reticulum. It is concluded that heterologous betaC1 protein can replace the movement function of the DNA B of a bipartite begomovirus. Evidence is also provided that tomato leaf curl virus encoded C4 protein confers the same movement function to ToLCNDV DNA A. The intracellular distribution of betaC1 is consistent with the hypothesis that it has a role in transporting the DNA A from the nuclear site of replication to the plasmodesmatal exit sites of the infected cell. PMID- 17872544 TI - Urinary excretion and blood level of prions in scrapie-infected hamsters. AB - Prions, infectious agents causing transmissible spongiform encephalopathy (TSE), are composed primarily of the pathogenic form (PrP(Sc)) of the host-encoded prion protein. Although very low levels of infectivity have been detected in urine from scrapie-infected rodents, no reports of urinary PrP(Sc) have been substantiated. Studies on the dynamics of urinary PrP(Sc) during infection are needed to ensure the safety of urine-derived biopharmaceuticals and to assess the possible horizontal transmission of prion diseases. Using the protein misfolding cyclic amplification technique, a time-course study of urinary excretion and blood levels of PrP(Sc) was performed in Sc237-infected hamsters and a high rate of PrP(Sc) excretion was found during the terminal stage of the disease. Following oral administration, PrP(Sc) was present in all buffy coat samples examined; it was also present in most of the plasma samples obtained from hamsters in the symptomatic stage. PrP(Sc) was excreted in urine for a few days after oral administration; subsequently, urinary PrP(Sc) was not detected until the terminal disease stage. These results represent the first biochemical detection of PrP(Sc) in urine from TSE-infected animals. PMID- 17872545 TI - Enteroglial and neuronal involvement without apparent neuron loss in ileal enteric nervous system plexuses from scrapie-affected sheep. AB - The enteric nervous system (ENS) probably plays a dominant role in sheep scrapie pathogenesis, but little is known about the cell types involved. We investigated the ileal myenteric and submucosal plexuses of four naturally and four orally experimentally scrapie-affected ARQ/ARQ Sarda sheep, as well as those of 12 healthy-control Sarda sheep carrying different PrP genotypes. All scrapie affected animals, euthanized at clinical-disease end stage, showed PrPd deposition within enteric glial cells (EGCs) and calbindin-immunoreactive (CALB IR) and neuronal nitric oxide synthase (nNOS)-IR neurons. Whole-mount investigations revealed no significant differences between the densities of total, CALB-IR and nNOS-IR neurons in scrapie-affected versus healthy sheep, irrespective of PrP genotype. Our results suggest that EGCs and CALB-IR and nNOS IR neurons are probably involved in the pathogenesis of natural and oral experimental sheep scrapie. Furthermore, the infectious agent may be less pathogenic towards ENS neurons than it is towards central nervous system neurons. PMID- 17872546 TI - Enzymatic detergent treatment protocol that reduces protease-resistant prion protein load and infectivity from surgical-steel monofilaments contaminated with a human-derived prion strain. AB - The unconventional nature of the infectious agent of prion diseases poses a challenge to conventional infection control methodologies. The extraneural tissue distribution of variant and sporadic Creutzfeldt-Jakob disease has increased concern regarding the risk of prion disease transmission via general surgical procedures and highlighted the need for decontamination procedures that can be incorporated into routine processing. In this study, the ability of preparations of enzymatic medical instrument cleaners to reduce the infectivity associated with a rodent-adapted strain of human prion disease, previously reported to be resistant to decontamination, was tested. Efficient degradation of the disease associated prion protein by enzymatic cleaning preparations required high treatment temperatures (50-60 degrees C). Standard decontamination methods (1 M NaOH for 1 h or autoclaving at 134 degrees C for 18 min) reduced infectivity associated with the human-derived prion strain by less than 3 log10 LD50. In contrast, a 30 min treatment with the optimized enzymatic cleaning preparation protocols reduced infectivity by more than 3 log10 LD50 and when used in conjunction with autoclave cycles eliminated detectable levels of infectivity. The development of prion decontamination procedures that are compatible with routine cleaning and sterilization of medical and surgical instruments may reduce the risk of the transmission of prion disease in general surgery. PMID- 17872547 TI - A medical malpractice tribunal experience. PMID- 17872548 TI - Clinical features and treatment prognosis of pathological gamblers with and without recent gambling-related illegal behavior. AB - A substantial proportion of pathological gamblers engage in gambling-related illegal behavior. We examined differences in baseline characteristics and treatment outcomes in two groups: pathological gamblers who did and did not commit gambling-related illegal acts in the year before treatment. Participants were 231 pathological gamblers enrolled in a randomized study of treatment that included cognitive behavior therapy and referral to Gamblers Anonymous (GA). Participants reporting recent illegal behavior (n = 63) endorsed more severe lifetime and recent (past-year) gambling disorder symptoms and higher gambling related debt than did gamblers who denied illegal behavior (n = 168). Those who reported illegal behavior also maintained a significantly higher severity of gambling disorder throughout treatment, although both groups experienced similar improvements in gambling symptoms over time. While pathological gamblers with or without gambling-related illegal behavior appeared to improve at a similar rate regardless of the treatment provided, more intensive treatment may be warranted for individuals with gambling-related illegal behavior, as they demonstrated greater gambling severity throughout treatment and follow-up. PMID- 17872549 TI - Commentary: illegal behavior and pathological gambling. AB - A complex relationship exists between illegal behavior and pathological gambling, and this relationship has significant implications in both the legal and clinical domains. Despite the importance of this relationship, relatively little research has examined illegal behavior in pathological gambling, particularly within a current gambling climate that has seen dramatic expansion over recent years. Although the article by Ledgerwood and colleagues provides additional insight into the relationship between pathological gambling and illegal behavior, many questions remain unanswered and warrant further investigation. PMID- 17872550 TI - Parricide: a comparative study of matricide versus patricide. AB - Between 1990 and 2005, 64 parents were killed by their children in the province of Quebec, Canada. The authors reviewed all consecutive coroners' files on these cases and found that 27 mothers and 37 fathers were the victims of parricide. The sample included 56 perpetrators: 52 sons and 4 daughters; 9 cases of double parricide were found. Approximately 15 percent of the perpetrators (8/56) attempted suicide following the parricide. A psychiatric motive (stemming from depression or psychotic illness) was determined for 65.5 percent (36/56) of the perpetrators, and 67 percent of them had a psychotic disorder. Similarities and differences were found between cases of matricide and patricide. PMID- 17872551 TI - Commentary: parricides unanswered questions, methodological obstacles, and legal considerations. AB - Unanswered questions about parricide abound. The scientific literature on parricide is modest and plagued by several methodological problems. In the present article, we seek to describe these problems, propose possible remedies, and review the legal considerations related to parricide. The rarity of the phenomenon creates significant barriers to the collecting of data about it. Moreover, generalization from any one study of parricide is also limited due to the low prevalence rate of the crime and ensuing difficulties with generating an unbiased sample of adequate size. The present article proposes strategies for accessing a statistically relevant sample size, in light of this low prevalence rate. Some of the remaining unanswered questions about parricide are also raised. Finally, legal questions surrounding criminal responsibility are explored. PMID- 17872552 TI - Inconsistency among American states on the age at which minors can consent to substance abuse treatment. AB - In a recent publication, the lack of consensus among U.S. laws regarding the age at which minors may consent to confidential treatment for abuse of illegal substances was highlighted. This article reports the results of an investigation of the information used by legislators to determine the age at which minors may consent to treatment. Evidence indicates that in four states lawmakers considered the advice of mental health professionals before making age determinations. In six states "consistency with other state laws" or "precedence" was the lawmakers' major consideration. In five states, the main concern was removing legal barriers to treatment access. Lawmakers from several states had no independent recollection regarding the motives behind age selection. When deciding on the age at which minors would be allowed to consent to substance abuse treatment, some state legislators based their decisions on clinical data or legal facts. Some, however, appear to have made decisions without a clear foundation. PMID- 17872553 TI - Commentary: legislators how did the deciders decide? Who shall serve as their experts? AB - Weisleder presents a retrospective empirical inquiry into the decision tree of state legislators who chose the age at which minors could consent to substance abuse treatment in their respective jurisdictions. Current medical practices and the developmental research into the cognitive capacities of adolescents did not figure prominently. Readers, including current and future political advocates, are provided with an informed window into the political processes of the making of a law that affects the practice of medicine. Weisleder is reminded that politics and science are uncomfortable bedfellows. PMID- 17872554 TI - The evolution of the american law institute test for insanity in Oregon: focus on diagnosis. AB - In 1962, the American Law Institute published its Model Penal Code, which includes an insanity test later adopted by many states. The second paragraph of the test excludes people with certain psychiatric conditions manifested by repeated criminal or antisocial conduct from using them as a basis for an insanity defense. Oregon adopted this test in 1971. Since then, its legislature and courts have added to the conditions excluded in the second paragraph. In this article, we look at how recent Oregon appellate court decisions have culminated in a narrower and less contentious notion of which psychiatric diagnoses serve as a basis for an insanity defense. Then we discuss Oregon's expansion of the second paragraph of the American Law Institute Insanity Test in a national context. PMID- 17872555 TI - Bad risk? An overview of laws prohibiting possession of firearms by individuals with a history of treatment for mental illness. AB - For nearly 40 years, federal law has barred certain individuals with a history of mental health treatment from purchasing, receiving, or possessing firearms. State laws are a patchwork of different regulations, some much more inclusive than the federal statute, others that parallel it closely. In some states, such laws are nonexistent. For the past 20 years, it has been possible to petition for relief from the federal prohibition; however, this is not the case with all state laws. The mechanisms for relief under state laws, when present, vary significantly, and not all require the input of a mental health professional or even of any physician. This article provides an overview of federal and state laws, a discussion of implications of these laws for mental health clinicians and forensic practitioners, and suggestions of directions for future research. PMID- 17872556 TI - Isaac ray at 200: phrenology and expert testimony. AB - In honor of Isaac Ray's 200th birthday, the author examines his early career for an example of critical thinking about expert testimony. Ray, a scientist from the outset, expressed interest in phrenology, a contemporary science of the mind. This paper explores a criminal case from Maine in which phrenological testimony was proffered and which Ray critiqued. The author then examines Ray's standards of practice in relation to present concepts of admissibility of expert testimony. He concludes that Ray's quality standards remain evident in contemporary efforts to apply evidence-based science to legal matters. PMID- 17872557 TI - Who is an expert? Competency evaluations in mental retardation and borderline intelligence. AB - Evaluations of competency to stand trial (CST) in defendants with mental retardation or borderline intellectual functioning can be difficult when deficits are masked by the type of adaptations seen in many with developmental disabilities. Accordingly, many evaluators have used validated test instruments, such as the CAST*MR (Competence Assessment to Stand Trial for Defendants with Mental Retardation) and tests measuring receptive and expressive language, to augment the clinical interview. The authors present a New Jersey case illustrating the need for clinicians to have adequate experience and training in some of the less known psychometric tests before presenting evidence in court. At the CST hearing, the judge disregarded the testimony of several psychologists while accepting that of a less experienced state's expert, we believe, to find the defendant competent. The finding was reversed on appeal. We encourage forensic professionals to be aware of the various instruments and minimum standards when employing specialized testing. PMID- 17872558 TI - The admissibility of expert evidence in Canada. AB - Recent decisions in Canadian Law suggest that it is evolving in a manner heavily influenced by American law. A recent Supreme Court decision uses the framework of prevailing law and superimposes the more stringent criteria enunciated in Daubert v. Merrell Dow Pharmaceuticals, Inc. We trace this development, reviewing the intervening cases that have contributed, and conclude with a summary of the law as it stands today. PMID- 17872559 TI - Crisis in the treatment of incompetence to proceed to trial: harbinger of a systemic illness. AB - Across the nation, a growing number of defendants judged incompetent to proceed (ITP) to trial are unable to access needed mental health care because of critical shortages of state hospital psychiatric beds and funding. Many of these patients languish in jails and prisons that lack the resources to provide adequate care during their prolonged wait for treatment. The crisis is yielding results that are medically, legally, and ethically unacceptable. The problem is presented as the latest symptom of an overwhelmed mental health system. Deficits across multiple domains are responsible for the current ITP logjam, creating an emergency that has been receiving increasing attention by medical and legal professionals, the media, and the public. Achieving meaningful and long-term solutions will necessitate recognizing the deficiencies in mental health capabilities within jails and prisons, courts of law, and communities, and addressing the dire need for the integration of these sectors. PMID- 17872560 TI - Too young to kill? U.S. Supreme Court treads a dangerous path in Roper v. Simmons. AB - The death penalty remains an intensely divisive topic in American society. Recently, there has been a series of cases, first involving defendants with mental retardation and more recently involving juveniles, in which the U.S. Supreme Court has ruled by a five-to-four margin that the death penalty in both these classes violates the Constitution's prohibition against cruel and unusual punishment guaranteed in the Eighth Amendment. In this essay, I explore the Supreme Court's recent decision in Roper v. Simmons, a case involving juveniles. Besides a more general discussion of the Supreme Court's decision and the biting dissent led by Justice Scalia, I focus on the reliance on foreign authorities in the Court's decision. I submit that irrespective of the moral arguments against the death penalty, reliance on foreign authorities in interpreting the U.S. Constitution is a dangerous trend, as it has long-term sovereignty implications for the United States. PMID- 17872562 TI - The IL23 axis plays a key role in the pathogenesis of IBD. AB - Exciting new results from a genetic study in humans and functional studies in mice have pinpointed interleukin 23 (IL23) and its receptor as a key pathway in the pathogenesis of inflammatory bowel disease (IBD). These findings reveal a hitherto unappreciated role for the IL23 axis in intestinal inflammation and may open new avenues for development of therapeutic strategies in IBD. PMID- 17872563 TI - Multiple liver lesions in a smoker. PMID- 17872564 TI - alpha2delta ligand: a new, smart pill for visceral pain in patients with hypersensitive irritable bowel syndrome? PMID- 17872565 TI - Latent coeliac disease or coeliac disease beyond villous atrophy? PMID- 17872566 TI - What is the role of iFOBT in screening for colorectal cancer? PMID- 17872567 TI - Antioxidants in acute pancreatitis. PMID- 17872568 TI - A cause of cholestatic jaundice. PMID- 17872569 TI - A huge intra-abdominal mass in a young man. PMID- 17872570 TI - Jaundice in a chronic hepatitis B carrier. PMID- 17872571 TI - Periportal and sinusoidal liver dendritic cells suppressing T helper type 1 mediated hepatitis. AB - BACKGROUND: Recently, we found that portal vein tolerance is associated with generation of Th2 cells and apoptosis of Th1 cells in the liver, which is regulated by antigen (Ag)-presenting dendritic cells (DCs) in the periportal area and sinusoids. AIM: In this study, we tested whether the periportal and sinusoidal DCs, which were loaded with an Ag in vivo, can inhibit liver injury caused by Th1 cells activated by the Ag administered systemically. METHODS: Ag specific hepatitis model was created by adoptively transferring ovalbumin (OVA) specific CD4(+) T cells to BALB/c mice and venous injection of OVA-containing liposomes. Liver CD11c(+) cells obtained from mice fed OVA were then transferred into these mice. RESULTS: The transfer of liver CD11c(+) cells from OVA-fed mice completely inhibited hepatic injury, which was associated with apoptosis of OVA specific CD4(+) T cells and emergence of Th2 cells in the liver. Transfer of CD11c(+) cells and subcutaneous OVA challenge led to enhancement of OVA-specific IgE Ab as well as Th2 cytokine responses in the recipient mice. CONCLUSIONS: Periportal and sinusoidal DCs loaded with an Ag in the portal vein can induce Th2 response in the liver and prevent hepatic injury caused by Th1 cells. PMID- 17872572 TI - A patient with dysphagia. PMID- 17872573 TI - Advances in counselling and surveillance of patients at risk for pancreatic cancer. PMID- 17872574 TI - Occult hepatitis B virus infection in patients with non-Hodgkin lymphoma: the need for early diagnosis in anti-Hbc positive patients. PMID- 17872575 TI - The morphine-prostigmine provocation (Nardi) test for sphincter of Oddi dysfunction: results in healthy volunteers and in patients before and after transduodenal sphincteroplasty and transampullary septectomy. PMID- 17872576 TI - Urine based detection of intestinal mucosal cell damage in neonates with suspected necrotising enterocolitis. PMID- 17872577 TI - Peutz-Jeghers syndrome polyps are polyclonal with expanded progenitor cell compartment. PMID- 17872578 TI - Lymphogranuloma venereum proctocolitis: mucosal T cell immunity of the rectum associated with chlamydial clearance and clinical recovery. PMID- 17872579 TI - Treatment of an atazanivir associated grade 4 hyperbilirubinaemia with efavirenz. PMID- 17872580 TI - Iron deficiency anaemia and perianastomotic ulceration as a late complication of ileal resection in infancy. PMID- 17872581 TI - Chemotherapy for mantle cell lymphoma. PMID- 17872582 TI - Irritable bowel syndrome and negative appendectomy. PMID- 17872583 TI - Does hyperhomocysteinaemia contribute to gastric carcinogenesis in Helicobacter pylori infected patients? PMID- 17872584 TI - Biofilms in the normal human large bowel: fact rather than fiction. PMID- 17872585 TI - Pregabalin decreases visceral pain and prevents spinal neuronal activation in rats. PMID- 17872586 TI - Single aetiology and dual associations of cardiac cancer. PMID- 17872587 TI - Relapse after treatment with peginterferon alpha-2b alone or in combination with lamivudine in HBeAg positive chronic hepatitis B. PMID- 17872588 TI - Thematic review series: skin lipids. The role of epidermal lipids in cutaneous permeability barrier homeostasis. AB - The permeability barrier is required for terrestrial life and is localized to the stratum corneum, where extracellular lipid membranes inhibit water movement. The lipids that constitute the extracellular matrix have a unique composition and are 50% ceramides, 25% cholesterol, and 15% free fatty acids. Essential fatty acid deficiency results in abnormalities in stratum corneum structure function. The lipids are delivered to the extracellular space by the secretion of lamellar bodies, which contain phospholipids, glucosylceramides, sphingomyelin, cholesterol, and enzymes. In the extracellular space, the lamellar body lipids are metabolized by enzymes to the lipids that form the lamellar membranes. The lipids contained in the lamellar bodies are derived from both epidermal lipid synthesis and extracutaneous sources. Inhibition of cholesterol, fatty acid, ceramide, or glucosylceramide synthesis adversely affects lamellar body formation, thereby impairing barrier homeostasis. Studies have further shown that the elongation and desaturation of fatty acids is also required for barrier homeostasis. The mechanisms that mediate the uptake of extracutaneous lipids by the epidermis are unknown, but keratinocytes express LDL and scavenger receptor class B type 1, fatty acid transport proteins, and CD36. Topical application of physiologic lipids can improve permeability barrier homeostasis and has been useful in the treatment of cutaneous disorders. PMID- 17872589 TI - Adipocyte differentiation-related protein reduces the lipid droplet association of adipose triglyceride lipase and slows triacylglycerol turnover. AB - Although neutral lipid storage droplets are ubiquitous in eukaryotic cells, very little is known about how their synthesis and turnover are controlled. Adipocyte differentiation-related protein (ADRP; also known as adipophilin) is found on the surface of lipid droplets in most mammalian cell types. To learn how ADRP affects lipid storage, we stably expressed the protein in human embryonic kidney 293 (HEK 293) cells, which express little endogenous ADRP. As expected, ADRP was targeted to the surface of lipid droplets and caused an increase in triacylglycerol (TAG) mass under both basal and oleate-supplemented conditions. At least part of the increased mass resulted from a 50% decrease in the rate of TAG hydrolysis in ADRP expressing cells. Furthermore, ADRP expression increased the fraction of total cellular TAG that was stored in lipid droplets. ADRP expression induced a striking decrease in the association of adipose triglyceride lipase (ATGL) and mannose-6-phosphate receptor tail-interacting protein of 47 kDa with lipid droplets and also decreased the lipid droplet association of several other unknown proteins. Transient expression of ADRP in two other cell lines also reduced the lipid droplet association of catalytically inactive ATGL. We conclude that the reduced lipid droplet association of ATGL and/or other lipases may explain the decrease in TAG turnover observed in ADRP-expressing HEK 293 cells. PMID- 17872590 TI - Appraisal of hepatic lipase and lipoprotein lipase activities in mice. AB - A variety of methods are currently used to analyze HL and LPL activities in mice. In search of a simple methodology, we analyzed mouse preheparin and postheparin plasma LPL and HL activities using specific polyclonal antibodies raised in rabbit against rat HL (anti-HL) and in goat against rat LPL (anti-LPL). As an alternative, we analyzed HL activity in the presence of 1 M NaCl, a condition known to inhibit LPL activity in humans. The assays were validated using plasma samples from wild-type and HL-deficient C57BL/6 mice. We now show that the use of 1 M NaCl for the inhibition of plasma LPL activity in mice may generate incorrect measurements of both LPL and HL activities. Our data indicate that HL can be measured directly, without heparin injection, in preheparin plasma, because virtually all HL is present in an unbound form circulating in plasma. In contrast, measurable LPL activity is present only in postheparin plasma. Both HL and LPL can be measured using the same assay conditions (low salt and the presence of apolipoprotein C-II as an LPL activator). Total lipase activity in postheparin plasma minus preheparin HL activity reflects LPL activity. Specific antibodies are not required. PMID- 17872591 TI - A rapid fluorescence assay for sphingosine-1-phosphate lyase enzyme activity. AB - Sphingosine-1-phosphate (S1P) lyase (SPL) catalyzes the conversion of S1P to ethanolamine phosphate and hexadecenal. This enzyme plays diverse roles in physiology and disease and, thus, may be useful as a disease marker and/or drug target. Unfortunately, the radioisotope-based assay currently used to quantify SPL activity is suboptimal. We have devised an assay using a commercially available omega(7-nitro-2-1,3-benzoxadiazol-4-yl)-d-erythro (NBD)-labeled fluorescent substrate. Alternatively, we provide a method for synthesis of the substrate from NBD-sphingosine. Enzyme activity is determined by following the formation of NBD-aldehyde product, which is isolated from unreacted substrate by lipid extraction and quantified after separation by HPLC using a C18 column. A fluorescent NBD-C18-sphingosine internal standard is used to control for extraction efficiency. The reaction is linear over 20 min and total protein concentrations of 20-200 mg/l. The sensitivity of the fluorescence assay is comparable to or better than that of the radioactive assay, and SPL levels as low as 8 pmol/mg/min were readily detected. Semicarbazide, a nonspecific SPL inhibitor, reduced SPL activity in vitro by approximately 70% using both standard and fluorescence methods. Product inhibition was not observed using ethanolamine phosphate and a commercially available source of hexadecenal. This method is suitable for quantifying SPL activity in a variety of cell and tissue sources. PMID- 17872592 TI - A mechanistic advance in understanding RSV pathogenesis, but still a long way from therapy. PMID- 17872593 TI - Surfactant for acute lung injury. PMID- 17872596 TI - Duty to deliver: producing more family medicine graduates who practise obstetrics. PMID- 17872598 TI - Is there a role for marijuana in medical practice? No. PMID- 17872599 TI - Is there a role for marijuana in medical practice? Yes. PMID- 17872602 TI - Clarifying hormone terminology. PMID- 17872603 TI - In it for profit? PMID- 17872604 TI - Important role in emergency contraception. PMID- 17872605 TI - Safety of codeine during breastfeeding: fatal morphine poisoning in the breastfed neonate of a mother prescribed codeine. AB - QUESTION: Recently a newborn died from morphine poisoning when his mother used codeine while breastfeeding. Many patients receive codeine for postlabour pain. Is it safe to prescribe codeine for nursing mothers? ANSWER: When a mother is an ultrarapid metabolizer of cytochrome P450 2D6, she produces much more morphine when taking codeine than most people do. In this situation, newborns might be exposed to toxic levels of morphine when breastfeeding. Options to reduce this risk include discontinuing codeine after 2 to 3 days of use and being aware of symptoms of potential opioid toxicity in both mothers and newborns. PMID- 17872606 TI - Does analgesia mask diagnosis of appendicitis among children? AB - QUESTION: Can analgesia be given safely to patients with suspected appendicitis prior to surgical evaluation without masking physical signs and symptoms? ANSWER: Withholding analgesia from patients with acute abdominal pain and suspected appendicitis is common. This practice, however, is not supported by published literature. Although a few trials have noted some changes in abdominal examination with analgesia, this has not been associated with any changes in patient outcome. If patients are in pain, analgesia is warranted. Larger multicentre trials are needed to establish practice guidelines. PMID- 17872607 TI - Practice tips. Endometrial biopsy. PMID- 17872608 TI - Communication tips. Time flies: patients' perceptions of consultation length and actual duration. PMID- 17872609 TI - [Alzheimer Disease]. AB - OBJECTIVE: Alzheimer disease (AD) is the most common form of dementia. There have been many advances in the pharmacological treatment of AD in recent years. This article discusses 2 of these advances: vascular prevention and a new molecule, memantine. QUALITY OF EVIDENCE: The conclusions and recommendations in this article are based on data from studies providing level I and level II evidence. MAIN MESSAGE: Recent data suggest that vascular disease plays an important role in the physiopathology of AD. Memantine is a non-competitive, low-affinity N methyl-D-aspartate receptor antagonist of glutamate that offers a very attractive efficacy and safety profile for treating moderate to severe AD. CONCLUSION: The prevention and treatment of vascular risk factors should be an integral part of the management of AD. For the treatment of moderate to severe AD, memantine is a new option that is effective and well tolerated. PMID- 17872610 TI - Approach to diagnosis and management of abnormal uterine bleeding. AB - OBJECTIVE: To present a primary care approach to evaluating and managing abnormal uterine bleeding. SOURCES OF INFORMATION: Literature searches were conducted on MEDLINE from 1996 to November 2004, EMBASE from 1996 to January 2005, the Cochrane Database of Systematic Reviews from the 4th quarter of 2004 to the 3rd quarter of 2005, guideline advisory committee databases, the Canadian Medical Association Infobase, and Clinical Evidence. The quality of evidence ranged from level I to III. MAIN MESSAGE: Premenopausal abnormal uterine bleeding can be ovulatory, anovulatory, or anatomic. A variety of hormonal and nonhormonal treatments are available. Patients' preferences, side effects, and physicians' comfort should be considered when making treatment decisions. One in 4 cases of endometrial carcinoma occur in premenopausal women, so it is important to investigate women with risk factors. While postmenopausal bleeding is most commonly caused by atrophic vaginitis, bleeding should be investigated to rule out endometrial and cervical carcinoma. CONCLUSION: A primary care approach to medical management of abnormal uterine bleeding can help family physicians treat most women in the office as well as help physicians know when to refer women for specialist care. PMID- 17872611 TI - On the witness stand: learning the courtroom tango. AB - OBJECTIVE: To summarize the steps primary care physicians should follow when they are asked to testify in court. To describe standard Canadian courtroom procedures and to suggest practical, tested ways to give successful expert testimony. SOURCES OF INFORMATION: I drew on personal experience from more than 750 trial appearances and the literature on effective testimony. MAIN MESSAGE: Family physicians are in a unique position to offer comprehensive and relevant medical information to judges and juries to assist them in legal decision making. To give effective expert testimony, physicians must recognize the differences between legal and medical "culture" and appreciate the basic rules and structure of courtroom evidence. Employing their skills as patient educators, family physicians can speak confidently about their patients' conditions and needs. CONCLUSION: Increasing demand for family physicians to testify in court requires that they equip themselves with a solid understanding of what expert status enables them to do and that they learn techniques for presenting clear and persuasive evidence. PMID- 17872612 TI - Improving diabetes management: structured clinic program for Canadian primary care. AB - PROBLEM BEING ADDRESSED: Adherence to diabetes treatment guidelines is often poor in primary care. OBJECTIVE OF PROGRAM: To introduce simple accessible interventions in our clinic to improve both physicians' adherence to diabetes treatment guidelines and patient outcomes. PROGRAM DESCRIPTION: A physician and a nurse practitioner used 3 interventions for diabetes care: 30-minute appointments, reminder telephone calls to patients, and standardized flow sheets. Evaluation of this structured program found that, after 3 years, these interventions had improved primary caregivers' adherence to diabetes care guidelines and several physiologic parameters in patients with diabetes (compared with outcomes of patients managed with the usual less structured approach). CONCLUSION: This program improved delivery of diabetes care in our clinic. We believe a similar approach could help other physicians and nurse practitioners in primary care practices increase their adherence to guidelines and improve the clinical outcomes of their patients. PMID- 17872613 TI - Home or away? Factors affecting where women choose to give birth. AB - OBJECTIVE: To investigate the factors that influence women to deliver their babies in small rural communities rather than in larger centres that have more comprehensive obstetric services, including cesarean section capability and epidural anesthesia. DESIGN: Self-administered survey. SETTING: Marathon, Ont, a rural community of 4500 in north western Ontario that offers low-risk obstetric services and has no local cesarean section capability. The closest referral centre, Thunder Bay, is 300 km away. PARTICIPANTS: Sixty-four women between 16 and 40 years old living in Marathon. MAIN OUTCOME MEASURES: The relative importance of personal and systemic factors and of beliefs that influence women to choose to give birth in Marathon rather than a larger centre. How well informed women are about local obstetric services. How likely women would be to choose to deliver in Marathon if they had low-risk pregnancies. RESULTS: Beliefs were more important than personal and systemic factors in influencing women's decisions. Respondents were moderately well informed about local obstetric services (mean proportion of correct responses was 66%). Most women with low-risk pregnancies would choose to deliver in Marathon (77.8%). CONCLUSION: For women in Marathon, beliefs are much more important than personal and systemic factors in influencing the decision to give birth in this small rural community. PMID- 17872614 TI - Inquiring minds: women's approaches to evaluating complementary and alternative therapies for menopausal symptoms. AB - OBJECTIVE: To examine how women gather, evaluate, and use information on complementary and alternative medicine (CAM) options for managing menopausal symptoms. DESIGN: Qualitative study. SETTING: Calgary, Alta. PARTICIPANTS: Twenty two women with a mean age of 52 years (range 42 to 58 years) who sought information on CAM therapies to manage menopausal symptoms. METHOD: In-depth semistructured interviews. Category coding and thematic analysis were used to interpret the data. MAIN FINDINGS: Four major themes emerged: how women gathered information, how they evaluated the information, how they used the information, and the challenges they experienced in making informed decisions. Information gathering was an on going process; as women's symptoms changed, their information needs changed also. Their preferred sources of information included physicians, CAM practitioners, staff at health food stores, and personal contacts. They sought information about the process of menopause and about both CAM and conventional treatments. Study participants were highly educated. Most of them systematically evaluated information from many sources using such criteria as whether information was biased, where the information came from, and whether the information was current. Information was used to validate their symptoms and to choose treatment based on cost-benefit analysis, risk-benefit analysis, and possible negative side effects or interactions between medications. Finding reliable information was considered a challenge due to structural or information related barriers. Several of the women cited a lack of time as a challenge: time to search for and evaluate information and the pressure of time to find relief from the symptoms of menopause. CONCLUSION: There is a need for reliable information about menopause and the risks and benefits of CAM options for menopausal symptoms in a format accessible to the range of women who will experience or are experiencing this transition. As a trusted source, family physicians have a role in disseminating this information. PMID- 17872615 TI - Hands on: is there an association between doing procedures and job satisfaction? AB - OBJECTIVE: To determine whether there is a relationship in family medicine between higher overall job satisfaction and doing a wider range of procedures. DESIGN: Secondary analysis of a population survey (mailed questionnaire) using multiple regression analysis. SETTING: Canadian family practices. PARTICIPANTS: Family physicians who responded to the 2001 National Family Physician Workforce Survey conducted by the College of Family Physicians of Canada and whose main practice settings were private offices or clinics, community clinics, community health centres, or academic family medicine teaching units. MAIN OUTCOME MEASURES: Family physicians' overall job satisfaction. The predictor variable was range of procedures performed, defined as the variety of procedures done by family physicians. Eight potential confounding variables were examined: age; sex; solo versus group practice; population served by practice (urban, semiurban, rural); number of medical services offered; teaching (yes, no); constraints to medical care services; and the balance of physicians' personal and professional commitments. RESULTS: Of 19,762 physicians who responded to the question on job satisfaction, 15.8% were dissatisfied, 54.3% were moderately satisfied, and 29.8% were very satisfied overall. In multiple regression analysis, when controlling for confounding variables, the range of procedures done by family physicians was significantly associated with overall job satisfaction (P = .0001). The larger the range of procedures, the more satisfied the physician. The percentage of those very satisfied ranged from 28.1% for family physicians who did only a few procedures (0 to 4) to 33.5% for those who did 10 or more procedures. Greater satisfaction was reported by very young and very old male physicians, those in solo practice, rural physicians, teachers, those who had fewer constraints to medical care services, and those who thought their balance of personal and professional commitments was about right. CONCLUSION: Family physicians might improve their overall job satisfaction by increasing the range of procedures they do. This modest association has not been described previously. PMID- 17872617 TI - Effectiveness of antipsychotics: is the CATIE trial a tsunami? PMID- 17872616 TI - Why medical students switch careers: changing course during the preclinical years of medical school. AB - OBJECTIVE: To determine why students switch their career choices during the preclinical years of medical school. DESIGN: Two questionnaires were administered: the first at the beginning of medical school and the second about 3 years later just before students entered clinical clerkship. SETTING: University of British Columbia, University of Alberta, University of Toronto, University of Ottawa, Queen's University, University of Western Ontario, University of Calgary, and McMaster University. PARTICIPANTS: Entering cohorts from 10 medical school classes at 8 Canadian medical schools. MAIN OUTCOME MEASURES: Proportion of students who switched career choices and factors that influenced students to switch. RESULTS: Among the 845 eligible respondents to the second survey, 19.6% (166 students) had switched between categories of family medicine and specialties, with a net increase of 1.2% (10 students) to family medicine. Most students who switched career choices had already considered their new careers as options when they entered medical school. Seven factors influenced switching career choices; 6 of these (medical lifestyle, encouragement, positive clinical exposure, economics or politics, competence or skills, and ease of residency entry) had significantly different effects on students who switched to family medicine than on students who switched out of family medicine. The seventh factor was discouragement by a physician. CONCLUSION: Seven factors appear to affect students who switch careers. Two of these factors, economics or politics and ease of residency entry, have not been previously described in the literature. This study provides specific information on why students change their minds about careers before they get to the clinical years of medical training. PMID- 17872618 TI - Reasons to research. PMID- 17872621 TI - Continuity of community. PMID- 17872626 TI - Owning up to medical errors. PMID- 17872627 TI - Stories for life: introduction to narrative medicine. PMID- 17872628 TI - Ethical consultation. PMID- 17872631 TI - Navigating a crossroads. PMID- 17872632 TI - Stoned by lack of evidence. PMID- 17872633 TI - Moving story. PMID- 17872634 TI - Is family medicine a specialty? No. PMID- 17872635 TI - Is family medicine a specialty? Yes. PMID- 17872638 TI - Exposure to sibutramine during pregnancy. AB - QUESTION: One of my patients who was taking sibutramine to lose weight found out that she had unexpectedly conceived. The medication was stopped as soon as she found out, about 5 weeks into the pregnancy. Is the baby at risk? Should the pregnancy be aborted? ANSWER: No data to date suggest that involuntary exposure to sibutramine during pregnancy carries major risk of congenital malformations. Nevertheless, this medication should be avoided whenever possible during pregnancy, as there is little information on its effects. PMID- 17872639 TI - Communication tips. Medication list: enhancing patients' knowledge and adherence. PMID- 17872640 TI - Practice tips. Model for counseling people in relationships. PMID- 17872641 TI - Ileoileal intussusception in an adult patient. PMID- 17872642 TI - Uterine fibroid embolization: CME update for family physicians. AB - OBJECTIVE: To review evidence supporting the use of uterine fibroid embolization (UFE) as an alternative to hysterectomy and myomectomy for managing uterine fibroids. QUALITY OF EVIDENCE: MEDLINE was searched using the MeSH terms embolization, therapeutic; leiomyoma; treatment outcome; pregnancy; and clinical trials. Most published studies on use of UFE for management of uterine fibroids provide level II evidence. MAIN MESSAGE: For 71% to 92% of patients, UFE is effective at alleviating fibroid-related symptoms. After UFE, fibroids are reduced in size by 42% to 83%. Patients' satisfaction with the procedure is high (>90%), and UFE is safe and has a low rate of major complications (1.25%). When compared with hysterectomy, UFE is associated with fewer major complications, shorter hospital stays, and faster recovery. Although successful pregnancy following UFE is possible, there is insufficient evidence to advocate use of UFE over myomectomy for management of uterine fibroids in women wishing to preserve fertility. CONCLUSION: For treatment of symptomatic uterine fibroids, UFE is a safe and effective nonsurgical alternative to hysterectomy and myomectomy. PMID- 17872644 TI - Errors and adverse events in family medicine: developing and validating a Canadian taxonomy of errors. AB - OBJECTIVE: To develop a taxonomy of errors derived solely from the content of error reports using Canadian data from the Primary Care International Study of Medical Errors. DESIGN: Secondary analysis of data from a descriptive, cross sectional, self-report survey. SETTING: Community-based family medicine clinics. PARTICIPANTS: Family physicians. INTERVENTION: Implementation of an error reporting system for family medicine. MAIN OUTCOME MEASURES: Type of error, type of causal factor. RESULTS: Six types of errors or adverse events (administrative, communication, diagnostic, documentation, medication, and surgical or procedural) and 10 causal factors (case complexity, discontinuity of care, failure to follow protocol or accepted practice, fatigue, gap in knowledge, high workload, insufficient information on pharmacologic properties of medication, medication side effects, relationship dynamics, and structural problems) were identified. CONCLUSION: Our taxonomy differs from that adopted by the Primary Care International Study of Medical Errors. We propose that our taxonomy is better suited for the purposes of family physicians reporting errors in Canada. PMID- 17872643 TI - Approach to managing undiagnosed chest pain: could gastroesophageal reflux disease be the cause? AB - OBJECTIVE: To highlight gastroesophageal reflux disease as a common cause of undiagnosed chest pain. SOURCES OF INFORMATION: Diagnostic considerations are based on information in peer-reviewed articles retrieved from MEDLINE. Studies had to be in English and involve at least 30 subjects. Population-based studies had to have a sample size of at least 300 and a response rate of at least 60%. Thirty-seven relevant articles were found. MAIN MESSAGE: Clinical management of patients presenting with diagnostically challenging chest pain starts with a careful search for coronary artery disease and other potentially life-threatening causes. Investigations must continue until the underlying disease is identified and symptoms have been effectively controlled. Ongoing symptoms of undiagnosed chest pain cause considerable suffering, impair quality of life, and add unnecessary costs to the health care system. In more than half the patients with undiagnosed chest pain, symptoms are caused by gastroesophageal disease. Empirical acid-suppressive therapy with a proton pump inhibitor can assist clinicians in identifying patients whose symptoms are acid-related. CONCLUSION: Many patients with undiagnosed chest pain can be managed in primary care, minimizing the need for referrals and costly investigations. PMID- 17872645 TI - Rewards and challenges of family practice: Web-based survey using the Delphi method. AB - OBJECTIVE: To identify and describe the important rewards and challenges that affect family physicians in Alberta. DESIGN: Web-based qualitative study using the Delphi method. SETTING: Province of Alberta. PARTICIPANTS: Twenty-eight family physicians practising in Alberta. METHODS: The study website presented a description of the project, ethical information, a calendar of events, and contact information. Delphi surveys and demographic questionnaires were password protected. Five rounds of surveys were conducted between May 2004 and January 2005. Participants were notified of each round of surveys and prompted by e-mail if they did not respond. FINDINGS Participants identified 8 key rewards and 9 key challenges. The research team identified 2 additional challenges that were validated by participants. In order of perceived importance, key rewards were providing diverse and comprehensive care; providing preventive care; having relationships with patients and their families; being an immersed witness to the human condition; providing continuity of care and receiving ongoing feedback; having flexibility and control of practice and job security; maintaining and acquiring skills and knowledge; teaching and sharing knowledge and gaining experience and mentoring. The challenges, in order of perceived need to be addressed, were workload and time pressures and meeting demands; the need to promote the rewards of family practice to those considering joining the profession; overhead and income inequities; getting respect from specialists; the need to ensure that the rewards identified are not adversely affected by primary care reform; lack of availability of specialists, procedures, tests, and other resources; running a practice as a small business; paperwork, telephone calls, and forms; maintaining and acquiring skills and knowledge; patients' expectations; and medicolegal issues, insurance paperwork, and dealing with medical claims related to motor vehicle accidents. CONCLUSION: The rewards and challenges reported by participants outline the positive and negative factors in family practice. The challenges provide a focus for further work. PMID- 17872646 TI - Prevention of neonatal group B streptococcal infection: approaches of physicians in Winnipeg, Man. AB - OBJECTIVE: To determine how family physicians in Winnipeg, Man, approach prevention of neonatal group B streptococcal (GBS) infection, what influences their decisions, and whether their decisions differ from those of local obstetricians. DESIGN: Population-based survey. SETTING: Family physicians' and obstetricians' practices in Winnipeg. PARTICIPANTS: Eighty-five physicians and residents with hospital labour floor privileges. MAIN OUTCOME MEASURES: Individual approaches to prevention of neonatal GBS infection, factors influencing choice of approach, and perceptions of neonatal GBS disease and universal prenatal GBS screening. RESULTS: About 66% of family physicians and their residents followed the Society of Obstetricians and Gynaecologists of Canada's (SOGC) guidelines for universal GBS screening and intrapartum antibiotic prophylaxis of all GBS carriers. This was significantly fewer than the 87% of obstetricians who followed these guidelines (P = .026). Obstetricians were more likely than family physicians to cite the literature as influencing their approach to neonatal GBS prevention (P < .001). Family physicians were more likely to cite the influence of peers and colleagues (P = .04). The incidence of neonatal GBS and its associated mortality were overestimated by 61% and 55% of obstetricians, and 66% and 57% of family physicians, respectively. Despite concerns about the risks and costs of universal GBS screening and intrapartum antibiotic prophylaxis, 92% of obstetricians and 79% of family physicians thought that the benefits of universal screening outweighed the concerns. About 24% of obstetricians and 30% of family physicians were theoretically willing to expose more than 10,000 women to intrapartum prophylactic antibiotics to prevent a single neonatal GBS-related death. CONCLUSION: Family physicians were less likely than obstetricians to follow current SOGC guidelines for prevention of neonatal GBS disease. This could reflect a different perspective on patient care. Family physicians want patients to be involved in screening decisions based on full disclosure of potential harm and benefit. PMID- 17872647 TI - Pregnancy after uterine artery embolization for fibroids. PMID- 17872648 TI - The extra mile. PMID- 17872651 TI - Supporting primary care: tool kit for the future. PMID- 17872657 TI - Hard to know: what is hard knowledge? PMID- 17872658 TI - A quantum leap in medicine. PMID- 17872659 TI - Becoming a general practitioner: where's the joy in that? PMID- 17872663 TI - Rebuttal: Is family medicine a specialty? No. PMID- 17872664 TI - Rebuttal: Is family medicine a specialty? Yes. PMID- 17872667 TI - Inadequate numbers. PMID- 17872668 TI - You've got mail. PMID- 17872670 TI - Teamwork. PMID- 17872671 TI - Different conclusions about memantine. PMID- 17872672 TI - Are new agents used to treat rheumatoid arthritis safe to take during pregnancy? Organization of Teratology Information Specialists (OTIS) study. AB - QUESTION: I have a patient planning pregnancy who has resistant rheumatoid arthritis that will require treatment with some of the "new" medications. Which ones are safe to use during pregnancy, and which ones do we know enough about to tell whether they are safe or not? ANSWER: For most new disease-modifying biologic medications, we have few data on safety. More and more reassuring data are accumulating on azathioprine and cyclosporine. When you treat this patient, you can help in gathering such data by contacting the Organization of Teratology Information Specialists' Autoimmune Disease in Pregnancy study through Motherisk at 877 311-8972. PMID- 17872673 TI - Treating children's cyclic vomiting. AB - QUESTION: One of my pediatric patients was diagnosed with cyclic vomiting syndrome, and the parents are understandably frustrated with the recurrent yet unpredictable episodes that control and disrupt their family life. Are there any effective treatments for this condition? ANSWER: There is currently no evidence based treatment regimen for cyclic vomiting syndrome. Pharmacologic remedies, according to anecdotal cases, retrospective reports, and open-label trials, have found that some antimigraine, antiemetic, prokinetic, and anticonvulsant agents have been effective. Management focuses on correct diagnosis of the syndrome, avoidance of potential triggers, prophylactic pharmacotherapy, and supportive care for children and their families during episodes. PMID- 17872674 TI - Communication tips. Self-disclosure during medical encounters. PMID- 17872675 TI - Practice tips. Pessary insertion: choosing appropriate patients. PMID- 17872676 TI - Opioid-induced neurotoxicity. PMID- 17872677 TI - Asymptomatic hypothyroidism and statin-induced myopathy. PMID- 17872679 TI - Single-dose intrathecal analgesia to control labour pain: is it a useful alternative to epidural analgesia? AB - OBJECTIVE: To examine the safety and efficacy of single-dose spinal analgesia (intrathecal narcotics [ITN]) during labour. QUALITY OF EVIDENCE: MEDLINE was searched and the references of 2 systematic reviews and a meta-analysis were reviewed to find articles on obstetric analgesia and pain measurement. The 33 articles selected included 14 studies, 1 meta-analysis, and 2 systematic reviews, all providing level I evidence. MAIN MESSAGE: The literature supports use of ITN as a safe and effective alternative to epidural anesthesia. The recent decrease in rates of episiotomies and use of forceps during deliveries means patients require less dense perineal anesthesia. The advantage of single-dose ITN is that fewer physicians and nurses are needed to administer it even though its safety and effectiveness are comparable with other analgesics. Use of ITN is associated with a shorter first stage of labour and more rapid cervical dilation. A combination of 2.5 mg of bupivacaine, 25 microg of fentanyl, and 250 microg of morphine intrathecally usually provides a 4-hour window of acceptable analgesia for patients without complications not anticipating protracted labour. The evolution in dosing of ITN warrants a re-examination of its usefulness in modern obstetric practice. CONCLUSION: Physicians practising modern obstetrics in rural and small urban centres might find single-dose ITN a useful alternative to parenteral or epidural analgesia for appropriately selected patients. PMID- 17872680 TI - Pathologic and physiologic phimosis: approach to the phimotic foreskin. AB - OBJECTIVE: To review the differences between physiologic and pathologic phimosis, review proper foreskin care, and discuss when it is appropriate to seek consultation regarding a phimotic foreskin. SOURCES OF INFORMATION: This paper is based on selected findings from a MEDLINE search for literature on phimosis and circumcision referrals and on our experience at the Children's Hospital of Eastern Ontario Urology Clinic. MeSH headings used in our MEDLINE search included "phimosis," "referral and consultation," and "circumcision." Most of the available articles about phimosis and foreskin referrals were retrospective reviews and cohort studies (levels II and III evidence). MAIN MESSAGE: Phimosis is defined as the inability to retract the foreskin. Differentiating between physiologic and pathologic phimosis is important, as the former is managed conservatively and the latter requires surgical intervention. Great anxiety exists among patients and parents regarding non-retractile foreskins. Most phimosis referrals seen in pediatric urology clinics are normal physiologically phimotic foreskins. Referrals of patients with physiologic phimosis to urology clinics can create anxiety about the need for surgery among patients and parents, while unnecessarily expanding the waiting list for specialty assessment. Uncircumcised penises require no special care. With normal washing, using soap and water, and gentle retraction during urination and bathing, most foreskins will become retractile over time. CONCLUSION: Physiologic phimosis is often seen by family physicians. These patients and their parents require reassurance of normalcy and reinforcement of proper preputial hygiene. Consultation should be sought when evidence of pathologic phimosis is present, as this requires surgical management. PMID- 17872681 TI - Typology of after-hours care instructions for patients: telephone survey and multivariate analysis. AB - OBJECTIVE: To develop a typology of after-hours care (AHC) instructions and to examine physician and practice characteristics associated with each type of instruction. DESIGN: Cross-sectional telephone survey. Physicians' offices were called during evenings and weekends to listen to their messages regarding AHC. All messages were categorized. Thematic analysis of a subset of messages was conducted to develop a typology of AHC instructions. Logistic regression analysis was used to identify associations between physician and practice characteristics and the instructions left for patients. SETTING: Family practices in the greater Toronto area. PARTICIPANTS: Stratified random sample of family physicians providing office-based primary care. MAIN OUTCOME MEASURES: Form of response (eg, answering machine), content of message, and physician and practice characteristics. RESULTS: Of 514 after-hours messages from family physicians' offices, 421 were obtained from answering machines, 58 were obtained from answering services, 23 had no answer, 2 gave pager numbers, and 10 had other responses. Message content ranged from no AHC instructions to detailed advice; 54% of messages provided a single instruction, and the rest provided a combination of instructions. Content analysis identified 815 discrete instructions or types of response that were classified into 7 categories: 302 instructed patients to go to an emergency department; 122 provided direct contact with a physician; 115 told patients to go to a clinic; 94 left no directions; 76 suggested calling a housecall service; 45 suggested calling Telehealth; and 61 suggested other things. About 22% of messages only advised attending an emergency department, and 18% gave no advice at all. Physicians who were female, had Canadian certification in family medicine, held hospital privileges, or had attended a Canadian medical school were more likely to be directly available to their patients. CONCLUSION: Important issues identified included the recommendation to use an emergency department as the sole source of AHC, practices providing no specific AHC instructions to their patients, and physicians' lack of acceptance of Telehealth. To improve AHC, new initiatives should build upon the existing system, changes should be integrated, and there should be a range of AHC options for patients and physicians. PMID- 17872682 TI - Violence involving intimate partners: prevalence in Canadian family practice. AB - OBJECTIVE: To investigate the prevalence of violence involving intimate partners among women visiting Canadian family practices and to assess participants' attitudes toward future use of computer-assisted screening for violence and other health risks. DESIGN: Self-report via written survey. SETTING: Group family practice clinic in inner-city Toronto, Ont. PARTICIPANTS: Women patients at least 18 years old who were fluent in English. MAIN OUTCOME MEASURES: Responses to questions about violence selected from the Abuse Assessment Screen and the Partner Violence Screen. Participants' attitudes toward computer-assisted screening as measured by the Computerized Lifestyle Assessment Scale (1 to 5) in the domains of benefits, privacy-barriers, interaction-barriers, and interest. RESULTS: Responses were received from 202 patients, 144 of whom were in current or recent relationships and completed the section on intimate-partner violence (IPV). The overall prevalence of IPV in current or recent relationships was 14.6%. Emotional abuse was reported by 10.4%, threat of violence by 8.3%, and physical or sexual violence by 7.6% of respondents. Emotional abuse was significantly associated with threat of violence and physical or sexual violence (P < or = .001). Analysis of responses to questions on computerized screening revealed that participants generally perceived it would have benefits (mean score 3.6) and were very interested in it (mean score 4.3). Those who reported experiencing IPV rated the benefits of computerized screening significantly higher than respondents without IPV experiences did (t 2.3, df 142, P < .05). Participants were "not sure" about barriers (mean score 3.0). Responses were similar in the 2 groups for the domains of interest, privacy-barriers, and interaction-barriers. CONCLUSION: The high rate of IPV reported by women attending family practices calls for physicians to be vigilant. Future research should examine ways to facilitate physicians' inquiry into IPV. The positive attitudes of our participants toward interactive computer-assisted screening indicates a need for more research in this area. PMID- 17872683 TI - Residents' use of case-based reflection exercises. AB - OBJECTIVE: Qualitative exploration of the experience of family practice residents in using semistructured case-based reflection exercises as a learning medium. DESIGN: Qualitative study using in-depth interviews. SETTING: Memorial University's Family Medicine Residency Program in St John's, Newfoundland. PARTICIPANTS: Graduates of the residency program who had taken part ina pilot project that involved completion of case-based reflection exercises as a medium for enhancing learning. METHOD: In-depth interviews were conducted with graduates who had used the reflection exercises during their postgraduate training. All participants were in active practice. All of the audiotaped interviews were transcribed verbatim. Thematic analysis continued until saturation was reached. MAIN FINDINGS Eight interviews were conducted that included 5 women and 3 men. Three themes emerged from the data analysis: effect on the learning process, effect on the patient-doctor relationship, and effect on the learner. CONCLUSION: The experience of using the reflection exercises appeared to affect how family practice residents learned. Three major themes emerged: the reflection exercises as a continuing education process offered participants a strategy for future learning in practice; the exercises offered a different perspective on the patient-doctor interaction that had doctors looking for cues to deeper meaning; and the exercises engaged the learners in a reflective process that revealed qualities about themselves that gave them personal insight. These reflective strategies have relevance for all physicians in their attempts to incorporate new knowledge and understanding into their practices. Similar dimensions are articulated in the educational literature, and this study supports the usefulness of case-based reflection as a catalyst in the education of family physicians. PMID- 17872684 TI - Where do family physicians practise after residency training? Flow of physicians from region to region across Canada. AB - OBJECTIVE: To understand the flow of family physicians from region to region across Canada. To discover how many leave a region after residency, how many stay, and how many flow into a region from other regions. DESIGN: Cross-sectional study using descriptive statistics. SETTING: Various regions across Canada. PARTICIPANTS: A weighted sample (N = 14,332) of all family physicians who completed the College of Family Physicians of Canada's 2001 National Family Physician Workforce Survey. This survey asked where physicians had done their family medicine residency. MAIN OUTCOME MEASURES: The proportion of family physicians whose current region of practice was the same as their place of residency ("staying"), the proportion of family physicians who trained in one region and who now practise in a different region ("outflow"), the proportion of family physicians who practise in a region but were trained in another region ("inflow"), and the number of family physicians flowing in and out of regions. RESULTS: Half of Canadian family physicians were practising in regions different from the regions where they did their residency programs. This percentage varied by region, however, with only Ontario's percentage resembling the Canadian figure. In the Atlantic and Prairie regions, few stayed (13.8% and 24.7%, respectively), but many flowed in. In Quebec, a high proportion stayed after residency training (81.6%). In British Columbia, only 23.7% stayed, but many flowed in. CONCLUSION: This study provides information about the relationship between where family physicians did their residency programs and where they subsequently practised. Our results add important information to the health human resource literature. PMID- 17872685 TI - COLD-fX. PMID- 17872686 TI - Step-by-step approach to managing pelvic organ prolapse: information for physicians. PMID- 17872687 TI - Gender equity: Canadian contribution to international initiative. PMID- 17872688 TI - Learning the simple things in Bolivia: reflections on an international health elective. PMID- 17872689 TI - The Afghan tailor. PMID- 17872692 TI - Waiting for a family doctor. PMID- 17872698 TI - An ounce of prevention: a pound of cure for an ailing health care system. PMID- 17872699 TI - International health and Canadian family practice: relevant to me, is it? PMID- 17872702 TI - Do beta-blockers have a role in treating hypertension? Yes. PMID- 17872703 TI - Do beta-blockers have a role in treating hypertension? No. PMID- 17872706 TI - Dutiful delivery. PMID- 17872707 TI - Sweet success. PMID- 17872708 TI - Culture-oriented health care. PMID- 17872709 TI - Thinking about errors. PMID- 17872710 TI - Take stories to heart. PMID- 17872711 TI - Breastfeeding and radiologic procedures. AB - QUESTION: Recently, some of my patients were instructed not to breastfeed for 24 to 48 hours after magnetic resonance imaging scans. Is this based on scientific evidence? ANSWER: No. On the contrary, evidence indicates unequivocally that the contrast media used for both magnetic resonance imaging and computed tomography scans are excreted into breast milk in such small quantities that there is no concern at all for nursing babies. PMID- 17872712 TI - Asymmetric ophthalmopathy in a hypothyroid patient. PMID- 17872713 TI - Communication tips. Feeling understood: expression of empathy during medical consultations. PMID- 17872714 TI - Practice tips. Inserting the levonorgestrel intrauterine system: off-label use. PMID- 17872715 TI - Managing prolactin-secreting adenomas during pregnancy. AB - OBJECTIVE: To determine an appropriate approach to managing prolactin-secreting adenomas of varying severity in pregnant women. SOURCES OF INFORMATION: MEDLINE was searched using the key words "hyperprolactinemia," "prolactinoma," "pregnancy," and "management." Experience from a multidisciplinary tertiary care centre was also reviewed. Recommendations are based on mostly levels II and III evidence. MAIN MESSAGE: With appropriate management, most women with hyperprolactinemia can achieve pregnancy. Although most women with prolactin secreting adenomas during pregnancy need only careful observation, others might require medical treatment or even surgical evacuation. Ideally, such patients should be managed by multidisciplinary teams. In the absence of such teams, most pregnant women with small tumours can be managed safely by their primary physicians. Those with large tumours should be referred to specialists. CONCLUSION: Family physicians play an important role in managing women with prolactinomas during pregnancy. Knowledge of current approaches to management is crucial in determining when and how to refer these patients. PMID- 17872716 TI - Cultivating interest in family medicine: family medicine interest group reaches undergraduate medical students. AB - PROBLEM ADDRESSED: Fewer medical students are choosing careers in family medicine across Canada. One way to cultivate student interest is through creation of family medicine interest groups. Students, residents, community-based family physicians, and academic faculty can all contribute to the success of such groups. OBJECTIVE OF PROGRAM: A family medicine interest group provides information about the challenging and rewarding career of family medicine through medical students' exposure to family physicians and residents. PROGRAM DESCRIPTION: A group of faculty and undergraduate students combined forces to form the Family Medicine Club. Development of this group and results of evaluation of its effectiveness to date are discussed. CONCLUSION: One mechanism to increase interest in primary care as a career is to initiate and foster a family medicine interest group that links students with family physicians. PMID- 17872717 TI - Diagnosing streptococcal sore throat in adults: randomized controlled trial of in office aids. AB - OBJECTIVE: To determine whether use of clinical decision rules or rapid streptococcal antigen detection tests (alone or in combination) can lower the number of unnecessary prescriptions for antibiotics for adults with acute sore throats. DESIGN: Four-arm randomized controlled trial. SETTING: Family practice offices in eastern Newfoundland. PARTICIPANTS: Forty urban and suburban family practitioners. INTERVENTIONS: Participants were randomly assigned to one of 4 arms (usual practice, decision rules only, rapid antigen test only, decision rules and antigen test combined), and each recruited successive adult patients presenting with acute sore throat as their main symptom. Following usual care or use of decision rules or rapid antigen tests or both (where applicable), physicians were to record what they prescribed for each patient. MAIN OUTCOME MEASURES: Prescribing rates and types of antibiotics prescribed. RESULTS: The prescribing rate using decision rules (55%) did not differ significantly from the rate using usual clinical practice (58%). Physicians using rapid antigen tests, both alone and with decision rules, had significantly lower prescribing rates (27% and 38%, respectively, both P < .001). CONCLUSION: Evidence-based clinical decision rules alone do not change family doctors' prescribing behaviour. Use of rapid antigen tests might allow physicians to persuade patients that negative results (and hence, viral infection) mean antibiotic therapy is not required. PMID- 17872718 TI - Asthma control in Canada: no improvement since we last looked in 1999. AB - OBJECTIVE: To determine whether asthma control in Canada had improved since the last major survey in 1999 by exploring how well patients' asthma was controlled, how much they knew about asthma control, and how they used health care resources. DESIGN: National telephone survey of patients between April and August 2004. SETTING: Canada. PARTICIPANTS: Eight hundred ninety-three adults 18 to 54 years old diagnosed with asthma more than 6 months before the survey. MAIN OUTCOME MEASURES: Patients' control of their asthma, patients' knowledge about asthma, the frequency and duration of periods of worsening asthma, and patients' use of health care resources to manage those periods. RESULTS: In total, 26,210 households listed in a consumer database were contacted. Excluding ineligible households and households with a language barrier, a member of 13% of the households completed the 35-minute survey. Based on definitions in Canadian guidelines, 53% of patients had symptomatic uncontrolled asthma. In the previous year, almost all asthma patients had experienced worsening of symptoms that lasted on average 13.6 days for patients with uncontrolled asthma and 8.0 days for patients with controlled asthma (P < .02). Markedly more patients with uncontrolled asthma used health care resources for episodes of asthma than patients with controlled asthma did (72% vs 15% for urgent office visits, P < .01; 32% vs 3% for emergency department visits, P < .01; and 7% vs 0% for hospitalizations, P < .01) in the year before the survey. Patients were confused about the differences between reliever and controller medications. One third of patients claimed that no one had taught them about asthma medications, and one quarter said they had received no training on how to recognize the early signs of asthma worsening. CONCLUSION: Asthma control and management remained suboptimal in Canada and relatively unchanged since the previous major survey in 1999. PMID- 17872719 TI - Far from ideal: weight perception, weight control, and associated risky behaviour of adolescent girls in Nova Scotia. AB - OBJECTIVE: To examine the prevalence of weight-related concerns, unhealthy weight control behaviour, and associated risky behaviour among adolescent girls, and to ascertain whether these girls had discussed a healthy weight with their physicians. DESIGN: Anonymous, self-report, cross-sectional survey. SETTING: Four high schools in rural Nova Scotia. PARTICIPANTS: Adolescent girls in grades 10 to 12. MAIN OUTCOME MEASURES: Weight perception, prevalence of weight-control behaviour, associations between weight perception and risky behaviour, associations between disordered eating behaviour and other risky behaviour. RESULTS: Overall response rate was 76%. Half the 1133 participants saw themselves as not being the "right" weight; 60% were trying to lose weight. During the past 30 days, 16% of the girls were attempting to control or lose weight and had engaged in disordered eating behaviour. In univariate analysis, perception of being either overweight or underweight was significantly associated with suicidal thoughts, suicide planning, and risk of depression. In multivariate analysis, positive associations were found between disordered eating behaviour and suicidal thoughts (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.6 to 6.7), suicide planning (OR 2.9, 95% CI 1.7 to 4.7), suicide attempts (OR 3.4, 95% CI 1.8 to 6.6), and ever having had vaginal intercourse (OR 1.6, 95% CI 1.1 to 2.5). Only 22% of respondents had spoken with a doctor about a healthy weight. CONCLUSION: Weight concerns are prevalent among adolescent girls in Nova Scotia. Many of them, especially those who see themselves as overweight or underweight, engage in unhealthy weight-control methods. Perceived underweight and overweight and disordered eating behaviour have strong associations with depression and self harming behaviour. Few participants had discussed a healthy weight with a physician. Health professionals should be aware of the associations between weight perception and disordered eating behaviour and other risky behaviour. PMID- 17872720 TI - The SMART study. PMID- 17872721 TI - Top 10 differential diagnoses in family medicine: Cough. PMID- 17872722 TI - Cervical cancer awareness and HPV prevention in Canada. PMID- 17872723 TI - Confidence and humility: our challenge to develop both during residency. PMID- 17872726 TI - Communities and primary care reform. PMID- 17872732 TI - Marketing family medicine: challenging misconceptions. PMID- 17872734 TI - Rebuttal: Do beta-blockers have a role in treating hypertension? Yes. PMID- 17872735 TI - Rebuttal: Do beta-blockers have a role in treating hypertension? No. PMID- 17872738 TI - Chest pain--consider panic disorder. PMID- 17872739 TI - When the law calls. PMID- 17872740 TI - Cause of confusion. PMID- 17872741 TI - Feeding stereotypes. PMID- 17872742 TI - Omega-3 fatty acid supplementation during pregnancy: for mother, baby, or neither? AB - QUESTION: Several pregnant patients have asked recently whether media reports of children's intelligence quotients' increasing with increased intake of essential fatty acids are meaningful enough to be worth the effort of supplementation. What advice should they be given? ANSWER: Existing evidence from interventional studies is sparse and conflicting and should not lead to supplementation with polyunsaturated fatty acids. PMID- 17872743 TI - Hypnosis for treatment of pain in children. AB - QUESTION: Many children suffer from chronic and painful illnesses. Hypnosis was found to be effective for analgesia in adults. Is it effective for managing pain in children? ANSWER: Children can be easier to hypnotize than adults. Studies have shown clinical hypnosis and self-hypnosis to be effective as adjunct treatments for children in pain. Examples include painful medical procedures, such as bone marrow aspiration and lumbar puncture in pediatric cancer patients, postoperative pain and anxiety in children undergoing surgery, and chronic headache. PMID- 17872744 TI - Communication tips. Reflecting back: empathic process. PMID- 17872745 TI - First-trimester bleeding with falling HCG: don't assume miscarriage. PMID- 17872746 TI - Practice tips. Smear tactics: a more comfortable Papanicolaou test. PMID- 17872748 TI - Managing nonalcoholic fatty liver disease: recommendations for family physicians. AB - OBJECTIVE: To review evidence on the diagnosis and management of nonalcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease in human beings. SOURCES OF INFORMATION: The literature was searched for clinical trials and review articles on NAFLD. Levels I and II evidence indicates the benefit of both lifestyle and pharmacologic interventions for NAFLD and nonalcoholic steatohepatitis (NASH). MAIN MESSAGE: Scientific evidence does not currently support systematic screening for NAFLD. Both NAFLD and NASH are frequently discovered in overweight and obese patients with asymptomatic elevation of serum aminotransferase levels. Ultrasonography detects the presence of a fatty liver, but is unreliable for detecting and quantifying liver fibrosis. Patients with NAFLD should be monitored for possible progression to NASH, particularly if they have diabetes or metabolic syndrome. Although diet and exercise are the mainstays of treatment, medication might be warranted if an appropriate diet and regular physical activity do not improve biochemical markers and liver morphology. Referral for liver biopsy and further evaluation should be considered for those at higher risk of developing NASH. CONCLUSION: Although most patients with NAFLD have a benign course, some progress to NASH, liver cirrhosis, and hepatocellular carcinoma. These patients should be carefully monitored for progression of disease and treated for associated metabolic disturbances. An integrated approach to care is essential. PMID- 17872749 TI - We don't live in igloos: Inuvik youth speak out. AB - OBJECTIVE: To determine what health problems concern youth in the Canadian North and what solutions these youths propose to address these problems by interviewing Inuvik youths, using their photographs to spark discussion. DESIGN: Qualitative study and photo-novella technique. SETTING: Inuvik, NWT, from July 1 to August 31, 2004. PARTICIPANTS: Thirty-five youths from Inuvik between the ages of 10 and 22. Two boys and 2 girls between the ages of 17 and 22 from the Inuvialuit and Gwich'in cultures featured in an educational video developed from the study. METHOD: Disposable cameras were distributed to 35 youths; interviews structured around the photographs were recorded with 14 youths. Thematic analysis of the interview transcripts was completed; the themes identified formed the basis of a 19-minute video featuring 4 of these youths. MAIN FINDINGS: Themes developed around mothers, culture, the land, and boredom. Specific health concerns identified were smoking, alcohol and drug abuse, and teen pregnancy. Solutions suggested included sources of recreation and distraction from substance abuse, such as a movie theatre, a shopping mall, and upgrades to the skatepark. CONCLUSION: By having Inuvik youths share their stories and perspectives, health care providers can gain insight into the issues and concerns of youth in northern communities and expand their capacity to heal. Photo novella is a useful method for research in adolescent health. PMID- 17872747 TI - Not enough vitamin D: health consequences for Canadians. AB - OBJECTIVE: To review the evidence on vitamin D (VTD) insufficiency and deficiency from a Canadian perspective and to highlight some of the known and evolving implications of insufficiency or deficiency for health. QUALITY OF EVIDENCE: PubMed was searched for articles on VTD insufficiency or deficiency and the role they play in various diseases and conditions. Level I and II evidence indicates that lack of VTD has a major role in short- and long-latency diseases. MAIN MESSAGE: The long winters in Canada and lack of exposure to the sun contribute to lower levels of VTD among Canadians in late winter and spring. Currently recommended levels of fortification and supplementation are likely not high enough to restore adequate levels of VTD in the body. Repletion and maintenance therapy might be needed. CONCLUSION: Many Canadians are at risk of VTD insufficiency or deficiency. Assessment of VTD status is important because optimal levels of VTD have been determined for various conditions. Low levels of VTD have negative implications for bone health and the health of other cell types. PMID- 17872750 TI - What women expect of family physicians as maternity care providers. AB - OBJECTIVE: To explore women's expectations and experiences of family physicians as maternity care providers. DESIGN: In-depth semistructured one-on-one interviews were conducted at 36 weeks' gestation and at 6 weeks postpartum. SETTING: Family practices in Halifax, NS. PARTICIPANTS: Five female family physicians recruited a total of 6 low-risk primigravida women. Five of the 6 women completed follow-up interviews. METHOD: Interviews lasting 1 to 2 hours were conducted using an unstructured interview guide. Interviews were audiotaped and transcribed verbatim. Data were analyzed using a grounded-theory approach. MAIN FINDINGS: Women's expectations fell into 4 main categories: informational support, emotional support, advocacy, and competent professional care. Women's expectations of physicians were consistent in some areas and varied in others. All women expected their physicians to communicate information about their medical care, listen to and respect their wishes, and provide them with competent medical care. Some women expected their physicians to provide emotional support and help with decision making, while others did not. Uncertainty about the role of family physicians in helping women prepare for birth was also evident. Women in our study described a range of roles for family physicians as maternity care providers. These roles reflected a holistic style of care that addresses the psychosocial as well as the biomedical needs of women giving birth. CONCLUSION: Research is needed to define family physicians' roles as maternity care providers and to describe how these roles fit with similar roles filled by other maternity care providers. PMID- 17872751 TI - Family medicine as a career option: how students' attitudes changed during medical school. AB - OBJECTIVE: To track and describe career choice decisions of medical students as they progressed through their undergraduate training. DESIGN: Quantitative survey of each class at 5 points during their undergraduate experience. Each survey collected qualitative descriptors of students' current career choices. SETTING: Faculty of Medicine at Memorial University of Newfoundland in St John's. PARTICIPANTS: Undergraduate medical students in each year from 1999 to 2006. MAIN OUTCOME MEASURES: Number of students considering family medicine as a career option at 5 different data-collection points throughout the medical school curriculum. RESULTS: Many students considered family medicine as a career choice early in their undergraduate experience. The number of students considering family medicine dropped significantly during the second year of the curriculum. This trend was consistent across all students surveyed. Although interest in family medicine as a career rebounded later in the curriculum, it never fully recovered. CONCLUSION: A large percentage of medical students considered family medicine as a career choice when they entered medical school. The percentage dropped significantly by the end of the second year of training. Attention should be directed toward understanding how the undergraduate medical curriculum in the first 2 years can protect and cultivate interest in family medicine as a career choice. PMID- 17872752 TI - Physicians as mothers: breastfeeding practices of physician-mothers in Newfoundland and Labrador. AB - OBJECTIVE: To determine the initiation rate and duration of breastfeeding among female physicians in Newfoundland and Labrador, and to identify demographic factors that might influence duration of breastfeeding in this population. DESIGN: Mailed survey. SETTING: Newfoundland and Labrador. PARTICIPANTS: One hundred eighty licensed female physicians. MAIN OUTCOME MEASURES: Self-reported initiation of breastfeeding for each baby born, duration of breastfeeding in number of months, and reasons for ending breastfeeding. RESULTS: The response rate was 68%. The breastfeeding initiation rate among respondents was 96.6%. More physicians who graduated in 1980 or later breastfed for longer periods (63.9% vs 33.3%, P = .008). More family doctors than specialists breastfed their babies for longer periods (65.5% vs 33.3%, P = .004). More physicians whose partners were working part-time breastfed for longer periods than physicians whose partners were working full-time (83.3% vs 50.8%, P = .037). Other factors, such as age, income, maternity leave and benefits, part-time or full-time work, and urban or rural practice, did not affect duration of breastfeeding. Personal issues accounted for 51% of respondents' ending breastfeeding; baby issues accounted for 38%, practice issues for 33%, medical school issues for 4%, and societal issues for 1%. CONCLUSION: The breastfeeding initiation rate among female physician respondents in Newfoundland and Labrador was 96.6%; more than 50% of these physicians breastfed for longer than 7 months. Physicians graduating in 1980 or later breastfed their babies for longer. PMID- 17872753 TI - Top 10 differential diagnoses in family medicine: Fatigue. PMID- 17872755 TI - Future perfect: the importance of family medicine teachers. PMID- 17872761 TI - A duty to certify death: helping family doctors meet their responsibilities. PMID- 17872763 TI - A terrible beauty: a physician's story of ovarian cancer. PMID- 17872764 TI - Should Canadians be offered systematic prostate cancer screening? Yes. PMID- 17872765 TI - Should Canadians be offered systematic prostate cancer screening? No. PMID- 17872768 TI - Ethical consultation. PMID- 17872769 TI - Managing uncertainty. PMID- 17872771 TI - The meaning of "is". PMID- 17872772 TI - Soft to know? PMID- 17872773 TI - Feminine fraternity. PMID- 17872774 TI - ITN requires training. PMID- 17872775 TI - Morphine in breast milk. PMID- 17872776 TI - A gulf of difference. PMID- 17872777 TI - Teratogenicity of lamotrigine. AB - QUESTION: One of my female patients has epilepsy and is currently receiving lamotrigine monotherapy. She has recently found that she is 6 weeks pregnant and is concerned about possible side effects of lamotrigine on her fetus. How should I advise her and should I switch to another antiepileptic drug? ANSWER: Lamotrigine (LTG) has not been associated with an increased risk for major malformations in monotherapy in most available studies. Risk of major malformations has been suggested when LTG was taken in doses higher than 200 mg/d and when clefts not caused by any known syndrome have been associated with LTG treatment. Therefore, safety for the fetus cannot yet be proven or rejected, although the drug does not appear to be a major human teratogen. PMID- 17872778 TI - Practice tips. Model of counseling for family doctors. PMID- 17872779 TI - The hand that writes the opioid.... PMID- 17872780 TI - Headache, palsy, and an elevated ESR: not necessarily giant cell arteritis. PMID- 17872781 TI - Prevalence, diagnosis, and treatment of ankyloglossia: methodologic review. AB - OBJECTIVE: To review the diagnostic criteria for, the prevalence of, and the effectiveness of frenotomy for treatment of ankyloglossia. DATA SOURCES: MEDLINE and CINAHL databases were searched for articles suitable for a methodologic review of studies on various aspects of ankyloglossia. STUDY SELECTION: Studies that presented data on patients and addressed ankyloglossia in relation to breastfeeding were selected. Case reports, case series, retrospective studies, prospective controlled studies, and randomized controlled trials were included in the analysis. Opinion pieces, literature reviews, studies without data on patients, studies that did not focus on breastfeeding, position statements, and surveys were excluded. SYNTHESIS: There is no well-validated clinical method for establishing a diagnosis of ankyloglossia. Five studies using different diagnostic criteria found a prevalence of ankyloglossia of between 4% and 10%. The results of 6 non-randomized studies and 1 randomized study assessing the effectiveness of frenotomy for improving nipple pain, sucking, latch, and continuation of breastfeeding all suggested frenotomy was beneficial. No serious adverse events were reported. CONCLUSION: Diagnostic criteria for ankyloglossia are needed to allow for comparative studies of treatment. Frenotomy is likely an effective treatment, but further randomized controlled trials are needed to confirm this. A reliable frenotomy decision rule is also needed. PMID- 17872782 TI - Death duties: workshop on what family physicians are expected to do when patients die. AB - PROBLEM BEING ADDRESSED: Family physicians are often called upon to pronounce and certify the deaths of patients. Inadequate knowledge of the Coroners Act (in the province of Ontario) and of the correct process of certifying death can make physicians uncomfortable when confronted with these tasks. OBJECTIVE OF PROGRAM: To educate family physicians about how to perform the administrative tasks required of them when patients die. PROGRAM DESCRIPTION: The program included an educational video, a tutorial outlining the process of death certification, and discussion with a regional coroner about key features of the Coroners Act. In small groups, participants worked through cases of patient deaths in which they were asked to determine whether a coroner needed to be involved, to determine the manner of death, and to complete a mock death certificate for each case. CONCLUSION: All participants reported a high level of satisfaction with the workshop and thought the main objective of the program had been achieved. Results of a test given 3 months after the workshop showed substantial improvement in participants' knowledge of the coroner's role and of the process of death certification. PMID- 17872783 TI - Polycystic ovary syndrome: validated questionnaire for use in diagnosis. AB - OBJECTIVE: To construct and validate a questionnaire for use in diagnosis of polycystic ovary syndrome (PCOS). DESIGN: All participants completed a questionnaire, which asked clinical questions designed to assist in the diagnosis of PCOS, before their appointments with an endocrinologist. Following completion of the questionnaire, the endocrinologist (blinded to the answers) made or excluded a diagnosis of PCOS using clinical criteria and biochemical data as indicated. Questions were then evaluated for their power to predict PCOS, and a model was constructed using the most reliable items to establish a system to predict a diagnosis of PCOS. SETTING: An outpatient reproductive endocrinology clinic in Calgary, Alta. PARTICIPANTS: Adult women patients who had been referred to the clinic. Fifty patients with PCOS and 50 patients without PCOS were included in the study. MAIN OUTCOME MEASURES: Demographic information, medical history, related diagnoses, menstrual history, and fertility history. RESULTS: A history of infrequent menses, hirsutism, obesity, and acne were strongly predictive of a diagnosis of PCOS, whereas a history of failed pregnancy attempts was not useful. A history of nipple discharge outside of pregnancy strongly predicted no diagnosis of PCOS. We constructed a 4-item questionnaire for use in diagnosis of PCOS; the questionnaire yielded a sensitivity of 85% and a specificity of 85% on multivariate logistic regression and a sensitivity of 77% and a specificity of 94% using the 4-item questionnaire. Predictive accuracy was validated using a second sample of 117 patients, in addition to internal validation using bootstrap analysis. CONCLUSION: We have constructed a simple clinical tool to help diagnose PCOS. This questionnaire can be easily incorporated into family physicians' busy practices. PMID- 17872784 TI - Canalith repositioning maneuver for benign paroxysmal positional vertigo: randomized controlled trial in family practice. AB - OBJECTIVE: To determine whether the canalith repositioning maneuver (CRM) is effective for treating benign paroxysmal positional vertigo when it is used by family physicians in primary care settings. DESIGN: Randomized, prospective, double-blind, sham-controlled trial. SETTING: An academic family practice in Hamilton, Ont. PARTICIPANTS: Eighty-one patients 18 years or older whose dizziness was confirmed by the Dix-Hallpike (DH) vertigo-triggering maneuver and who had no contraindications to the CRM. INTERVENTIONS: At the first visit, the intervention group received the CRM and the control group received a sham maneuver. Both groups received the CRM at the second and third visits 1 and 2 weeks later. MAIN OUTCOME MEASURES: Negative results of the DH test or self reported resolution of vertigo after the initial treatment. RESULTS: Eighty-one patients were randomized and received the first treatment. After the first treatment, 34.2% of patients in the intervention group and 14.6% of patients in the control group had negative DH test results (relative risk 2.3, 95% confidence interval 1.03 to 5.2, P = .04); and 31.6% of patients in the intervention group and 24.4% of patients in the control group reported resolution of dizziness (relative risk 1.2, 95% confidence interval 0.7 to 1.9, P = .48). One week later, patients in both intervention and control groups received the CRM, and 61.8% and 57.1% of them, respectively, had negative DH test results (P = .81). By week 3, approximately 75% of patients in both groups had improved. CONCLUSION: A statistically significant proportion of patients in the CRM group returned to a negative response to the DH maneuver immediately after the first treatment. Family physicians can use the CRM to treat benign paroxysmal positional vertigo and potentially avoid delays in treatment and unnecessary referrals. TRIAL REGISTRATION NUMBER: NCT00182273 (ClinicalTrials.gov). PMID- 17872785 TI - Epidemiology of early-onset neonatal group B streptococcal infection: implications for screening. AB - OBJECTIVE: To determine the difference in outcomes between universal screening and risk-based assessment for prenatal group B streptococcus (GBS) infection based on the epidemiology of early-onset GBS infection in Winnipeg, Man, and to examine its implications for prenatal GBS screening. DESIGN: Retrospective random chart audit of 330 women receiving intrapartum hospital care and retrospective chart audit of all infants with early-onset neonatal GBS disease over 2 years. SETTING: Each of the 3 hospitals in Winnipeg, Man, offering intrapartum services. MAIN OUTCOME MEASURES: Maternal charts were audited for history of prenatal GBS screening, GBS status, clinical risk factors for neonatal GBS transmission, and use of intrapartum antibiotics to prevent neonatal GBS infection. Neonatal GBS records were audited for maternal clinical risk factors for GBS transmission, history of maternal GBS screening and GBS status, use of maternal intrapartum antibiotic prophylaxis, and neonatal outcome. RESULTS: Screening revealed a 26% GBS carrier rate in our population. Among these carriers, 70% (or 18% of the population) had no other clinical risk factors for neonatal GBS transmission. The transmission rate for untreated GBS-positive women was 1.74 per 1000 women. The differences in outcomes between universal and risk-based screening were small in our population. A total of 3449 women would require universal screening to prevent a single case of early-onset neonatal GBS disease that would occur if a risk-based approach were used (3 cases per year). This number increases to 68,966 to prevent a single GBS-related death (1 case in 7 years). An additional 679 women would receive intrapartum prophylactic antibiotics per year with universal screening than would have received antibiotics with a risk-based approach. CONCLUSION: The differences in neonatal GBS transmission rates resulting from universal versus risk-based screening in Winnipeg require universal screening of many women for results to become apparent. Universal screening and antibiotic prophylaxis of all GBS carriers result in increased antibiotic exposure in our population, which might carry its own risks. Therefore, patients should be involved in decisions on whether to be screened based on identification of risks and benefits. PMID- 17872787 TI - Top 10 differential diagnoses in family medicine: Low back pain. PMID- 17872786 TI - Room for improvement: patients' experiences of primary care in Quebec before major reforms. AB - OBJECTIVE: To investigate variations in accessibility, continuity of care, and coordination of services as experienced by patients in Quebec on the eve of major reforms, and to provide baseline information against which reforms could be measured. DESIGN: Multilevel cross-sectional survey of practice. SETTING: One hundred primary health care settings were randomly selected in urban, suburban, rural, and remote locations in 5 health regions in Quebec. PARTICIPANTS: In each clinic, we chose up to 4 physicians and 20 consecutive patients consulting each physician. MAIN OUTCOME MEASURES: Patients' responses to a self-administered questionnaire, the Primary Care Assessment Tool, that assessed patient-provider affiliation, accessibility, relational continuity, coordination of primary and specialty care, and whether patients received health promotion and preventive services. RESULTS: A total of 3441 patients participated (87% acceptance rate) in 100 clinics (64% response rate). Timely access was difficult; only 10% expressed confidence they could be seen by their regular doctors within a day if they became suddenly ill. Average waiting time for a doctor's appointment was 24 days. Coordination of care with specialists was at minimally acceptable levels. Patients with family physicians recalled them addressing only 56% of the health promotion and preventive issues appropriate for their age and sex, and patients without family physicians recalled physicians addressing substantially fewer (38%). Most patients reported they were highly confident that their physicians knew them well and would manage their care beyond clinical encounters (relational continuity). The exception was the 16% of patients overall who did not have family physicians (34% of patients at walk-in clinics). CONCLUSION: This survey highlights serious problems with accessibility. Improvement is needed urgently to avoid deterioration of patients' confidence in the health system even though patients rate their relationships with their physician highly. Health promotion, preventive services, and coordination with specialists also needed to be improved, and careful thought must be given to the plight of those without family physicians. PMID- 17872788 TI - Adding evidence: the value of researching family medicine interest groups. PMID- 17872790 TI - The evolution of family medicine. PMID- 17872796 TI - Obesity, legal duties, and the family physician. PMID- 17872797 TI - Head first: bicycle-helmet use and our children's safety. PMID- 17872800 TI - Rebuttal: Should Canadians be offered systematic prostate cancer screening? NO. PMID- 17872801 TI - Rebuttal: Should Canadians be offered systematic prostate cancer screening? YES. PMID- 17872804 TI - Medical sleuthing without an MRI. PMID- 17872805 TI - Competing interests? PMID- 17872807 TI - Common misdiagnosis. PMID- 17872808 TI - Intraoperative floppy iris syndrome associated with tamsulosin. PMID- 17872809 TI - We cannot market the unsaleable. PMID- 17872811 TI - Practice tips. Life insurance applications: helping you to help your patients. PMID- 17872810 TI - Exposure to attention deficit hyperactivity disorder medications during pregnancy. AB - QUESTION: An 18-year-old patient of mine, currently under treatment for attention deficit hyperactivity disorder (ADHD) with methylphenidate, just found out that she is pregnant. What are the risks for the baby when the mother uses ADHD medications during pregnancy? ANSWER: Available evidence for amphetamines suggests no increased risk of malformations with use of therapeutic doses, and inadvertent exposure during pregnancy is unlikely to be harmful. Human data for methylphenidate and atomoxetine treatment in pregnancy are very limited. Documented cases do not suggest teratogenicity, but we cannot rule out this risk with the information available. PMID- 17872812 TI - Carpal tunnel syndrome and vitamin B6. AB - QUESTION: A 42-year-old woman with carpal tunnel syndrome tells you she has started taking a vitamin B6 supplement to relieve her symptoms. Her work in an automotive parts department involves both lifting moderately heavy packages and typing at a computer terminal. What does the research indicate about vitamin B6 as a treatment option, and what health issues should you discuss with this patient? ANSWER: Although its effectiveness is controversial, vitamin B6 is often used as a conservative and adjunct therapy in treatment of carpal tunnel syndrome. Many patients attempt to treat their symptoms with vitamin B6 on their own. Vitamin B6 at less than 200 mg daily is not likely to cause any adverse effects, but patients should be monitored for changes in symptoms, particularly when high doses are taken over long periods. PMID- 17872813 TI - Back stab: percutaneous vertebroplasty for severe back pain. AB - OBJECTIVE: To review the evidence supporting use of percutaneous vertebroplasty for relief of pain and mechanical stability in patients with vertebral compression fractures unrelieved by conventional measures. QUALITY OF EVIDENCE: Ovid MEDLINE was searched from January 1966 to December2006 for all English language papers on vertebroplasty. The quality of evidence in these papers was graded according to the 4-point classification system of evidence-based medicine. Level II evidence currently supports use of vertebroplasty. MAIN MESSAGE: Vertebroplasty alleviates pain from vertebral compression fractures that result from osteoporosis, hemangiomas, malignancies, and vertebral osteonecrosis. Vertebroplasty has provided substantial pain relief in 60% to 100% of patients; has decreasedanalgesic use in 34% to 91% of patients; and has improved physical mobility in 29% to 100% of patients. Contraindications to vertebroplasty include asymptomatic compression fractures of the vertebral body, vertebra plana, retropulsed bone fragments or tumours, active infection, uncorrectable coagulopathy, allergy to the bone cement or opacification agent, severe cardiopulmonary disease, pregnancy, and pre-existing radiculopathy. The short term complication rate was found to be 0.5% to 54%. Rare but serious complications include compression of the spinal cord or nerve root, infection, cement embolization causing pulmonary infarct and clinical symptoms, paradoxical embolization of the cerebral artery, and severe hematomas. CONCLUSION: Vertebroplasty is a safe and effective treatment for vertebral fractures that cannot be treated using conservative measures. PMID- 17872814 TI - Approach to managing musculoskeletal pain: acetaminophen, cyclooxygenase-2 inhibitors, or traditional NSAIDs? AB - OBJECTIVE: To provide family physicians and pharmacists with practical, evidence- and expertise-based guidance on choosing the safest approach to using analgesics to manage patients with musculoskeletal pain. SOURCES OF INFORMATION: Health care providers from family practice, rheumatology, gastroenterology, hepatology, internal medicine, and pharmacy participated in an educational needs assessment regarding the management of pain and the safety of commonly used analgesics. Feedback from one-on-one interviews was compiled and distributed to participants who selected key topics. Topics chosen formed the basis for the discussions of this multidisciplinary panel that reviewed data on the safety of analgesics, particularly in regard to comorbidity and concurrent use with other therapies. MAIN MESSAGE: Treatment should begin with an effective analgesic with the best safety profile at the lowest dose and escalate to higher doses and different analgesics as required. Acetaminophen is a safe medication that should be considered first-line therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with potential adverse gastrointestinal, renal, hepatic, and cardiovascular effects. Physicians should not prescribe NSAIDs before taking a careful history and doing a physical examination so they have the information they need to weigh the risks (adverse effects and potential drug interactions) and benefits for individual patients. CONCLUSION: Taking a complete and accurate history and doing a physical examination are essential for choosing the safest analgesic for a particular patient. PMID- 17872815 TI - Treatments for carpal tunnel syndrome: who does what, when ... and why? AB - OBJECTIVE: To determine how frequently treatments had been offered to patients with suspected diagnoses of carpal tunnel syndrome (CTS) who had been referred for confirmatory nerve conduction studies (NCSs) and to identify potential predictors of such treatment. A follow-up survey was conducted to determine the effect of NCS results on subsequent treatment. DESIGN: Self-administered survey questionnaire and follow-up telephone survey. SETTING: Royal University Hospital at the University of Saskatchewan in Saskatoon. PARTICIPANTS: Two hundred eleven patients with clinically suspected CTS who had been referred for confirmatory NCS. MAIN OUTCOME MEASURES: Results of NCSs, number of patients prescribed wrist splints or nonsteroidal anti-inflammatory drugs (NSAIDs) before and after NCSs, patient characteristics associated with being prescribed therapy, and reporting benefit of therapy. RESULTS: Nerve conduction studies confirmed CTS in 121 (57.3%) of the 211 study patients. Before NCSs, wrist splints and NSAIDs had been prescribed to 33.2% and 38.8% of patients, respectively. Splints and NSAIDs were reported to alleviate symptoms by 78.3% and 74% of patients, respectively, who received such treatments. No significant differences in age, sex, body mass index, symptom duration, symptom or function scores, or subsequent NCS results were noted between patients who were and were not prescribed these therapies or between those who did or did not report improvement in symptoms. Results of the follow-up survey indicated that the number of recommendations for splints and NSAIDs had doubled after NCSs were completed and that surgical intervention had been at least discussed in most cases. Treatment recommendations, including surgery, however, were not associated with identifiable patient factors, including patients' NCS results. CONCLUSION: Some patients were prescribed conservative treatments before NCSs. Following NCSs, prescriptions for wrist splints or NSAIDs approximately doubled. Interestingly, NCS results did not appear to influence subsequent therapeutic decision-making for either conservative treatment or surgical options. We think these findings suggest a lack of confidence in electrodiagnostic study results. It would be interesting to evaluate a larger population of primary care patients prospectively to examine further the use of NCSs in current clinical decision-making. PMID- 17872817 TI - Family health teams: can health professionals learn to work together? AB - OBJECTIVE: To learn what educators across the health professions involved in primary health care think about the use and development of academic family health teams to provide, teach, and model interprofessional collaboration and about the introduction of interprofessional education (IPE) within structured academic primary care. DESIGN: Qualitative study using focus groups. SETTING: Higher education institutions across Ontario. PARTICIPANTS: Purposeful sample of 36 participants from nursing, pharmacy, speech language pathology, occupational and physical therapy, social work, and family medicine. METHOD: Participants were invited to join focus groups of 6 to 8 health professionals. Themes were derived from qualitative analysis of data gathered using a grounded-theory approach. MAIN FINDINGS: Three major themes were identified: the lack of consensus on opportunities for future academic family health teams to teach IPE, the lack of formalized teaching of interprofessional collaboration and the fact that what little has been developed is primarily for family physicians and hardly at all for other health professionals, and the confusion around the definition of IPE across health professions. CONCLUSION: The future role of family health teams in academic primary care settings as a place for learners to see teamwork in action and to learn collaboration needs to be examined. Unless academic settings are developed to provide the necessary training for primary health care professionals to work in teams, a new generation of health care professionals will continue to work in status quo environments, and reform initiatives are unlikely to become sustainable over time. PMID- 17872816 TI - Validation of self-reported history of colorectal cancer screening. AB - OBJECTIVE: This study aims to determine the validity of self-reported history of colorectal cancer (CRC) testing consisting of fecal occult blood tests (FOBTs)in the past 2 years or endoscopy (flexible sigmoidoscopy or colonoscopy) in the past 5 years by comparing it with reports provided by physicians. DESIGN: A cross sectional design was used for this study. SETTING: Study participants were selected directly from the city's population. Self-reported history of CRC testing was validated using records obtained from their physicians' offices. PARTICIPANTS: Participants were adults of 50 to 74 years, living within the boundaries of Calgary Health Region in Alberta. INTERVENTIONS: Participants were recruited by a random-digit dial telephone survey of adults aged 50 to 74 years (n = 598). Following a phased process, a subset of these people (n = 200) agreed to provide names of their physicians to be contacted for their histories of CRC testing. Physicians' reports were used to measure validity of self-reported history. MAIN OUTCOME MEASURES: Agreement between self-reported history and physician's records was measured using kappa statistics and concordance. Validity of self-report was measured by calculating sensitivity, specificity, positive predictive values, and negative predictive values. Reasons for testing reported by the participants were compared with those reported by their physicians. RESULTS: Complete information was received for 146 participants, revealing a 34.2% testing rate for CRC. Intermediate level of agreement for testing history (kappa = 0.66 and concordance = 84.9%) was found between the 2 types of reporting for CRC testing. Self-reported history showed sensitivity of 76.0% (95% CI = 61.8%-86.9%) and specificity of 89.6% (95% CI = 81.7%-94.9%). High specificity was also observed for self-reporting of the individual tests, but low sensitivity was seen for the reporting of FOBT in the last 2 years. Most participants who correctly recalled the testing history also accurately identified the reason for testing (concordance = 80.0% for FOBT and 69.6% for endoscopy). CONCLUSION: Self reported history of CRC testing and physicians' reports showed dependable agreement. Physicians need to probe their patients further for the history of FOBT. These results can be useful in clinical practice to determine the CRC screening status of the patients. PMID- 17872819 TI - Top 10 differential diagnoses in family medicine: fever. PMID- 17872818 TI - First benzodiazepine prescriptions: qualitative study of patients' perspectives. AB - OBJECTIVE: To explore patients' views and expectations regarding their first prescription for benzodiazepines (BZDs). DESIGN: Qualitative study using semistructured interviews. SETTING: Patients were recruited from general practices in the regions of Ghent and Brussels in Belgium and were interviewed at home. PARTICIPANTS: Fifteen family practice patients who had received prescriptions for BZDs for the first time. METHOD: Interviews were audiotaped and transcribed verbatim. Data were analyzed by themes using a phenomenologic approach. MAIN FINDINGS: Patients had asked their physicians for "something" because they thought they were in serious distress and needed help. They seemed to feel a conflict between the need for medication and the negative connotations surrounding BZD use. Patients used 2 strategies to justify consumption of BZDs: maximizing their problems and minimizing use. Patients knew very little about the medication and did not ask about it. Their expectations regarding continued use were vague, even though they seemed to be aware of the risk of psychological dependency and conditioning mechanisms. Patients did not actively ask for nonpharmacologic alternatives, but when they were offered them, their attitudes toward them were generally positive. CONCLUSION: First-time BZD users ask for help with distress, but place the responsibility for solving their problems on their family physicians. Even when short-term users were aware of the concept of psychological dependency, they did not feel the need for more information. Physicians should develop communication strategies to persuade their patients that they take the patients' problems seriously even though consultations do not always end with prescriptions. It is important that doctors clearly explain the risks and benefits of starting BZD treatment and set limits from the start. This will help doctors manage first-time BZD users more effectively and will help patients avoid chronic use. PMID- 17872820 TI - Treating metabolic syndrome: lifestyle change or medication? PMID- 17872825 TI - Research in family medicine. PMID- 17872822 TI - It was time to go back. PMID- 17872831 TI - What to do with stories: the sciences of narrative medicine. PMID- 17872832 TI - Interpreting people as they interpret themselves: narrative in medical anthropology and family medicine. PMID- 17872833 TI - From narrative wreckage to islands of clarity: stories of recovery from psychosis. PMID- 17872834 TI - From suffering to transcendence: narratives in palliative care. PMID- 17872835 TI - Literature and medicine: exploring Margaret Atwood's short story "death by landscape". PMID- 17872836 TI - An extraordinary moment: the healing power of stories. PMID- 17872837 TI - Doctor as story-listener and storyteller. PMID- 17872838 TI - Should we avoid beta-agonists for moderate and severe chronic obstructive pulmonary disease? YES. PMID- 17872839 TI - Should we avoid beta-agonists for moderate and severe chronic obstructive pulmonary disease? NO. PMID- 17872842 TI - Should we treat strep throat with antibiotics? PMID- 17872843 TI - Recommend omega-3 fatty acids in pregnancy? PMID- 17872844 TI - Cost of fetal alcohol spectrum disorder in Canada. AB - QUESTION: I have heard that thousands of Canadian kids are affected by fetal alcohol spectrum disorders. Has there been any attempt to estimate what it costs our society? ANSWER: In a recent Canadian study, the lifetime cost of fetal alcohol spectrum disorders was estimated at $1 million per case. With an estimated 4000 new cases yearly, this translates to $4 billion annually. PMID- 17872845 TI - Practice tips. Rule of thumb: update on first carpometacarpal joint osteoarthritis. PMID- 17872846 TI - Mild infectious mononucleosis presenting with transient mixed liver disease: case report with a literature review. PMID- 17872847 TI - Factors that influence engagement in collaborative practice: how 8 health professionals became advocates. AB - OBJECTIVE: To generate hypotheses regarding factors that might influence engagement in collaborative practice. DESIGN: Qualitative study using in-depth interviews. SETTING: Participants interviewed each other in dyads. The pairing was based upon geographical location and proximity to each other. PARTICIPANTS: Eight professionals from the disciplines of medicine, nursing, occupational therapy, physical therapy, and massage therapy. METHOD: Semistructured interviews, lasting 30 to 45 minutes each, were recorded and transcribed verbatim. The transcripts were read by all research team members using independent content analysis for common words, phrases, statements, or units of text for key themes. At a subsequent face-to-face meeting, the team used an iterative process of comparing and contrasting key themes until consensus was reached. The transcripts were then analyzed further for subthemes using NVivo software. MAIN FINDINGS: Initial findings suggest that some common characteristics grounded in family history, school experiences, social interactions, and professional training might influence collaborative practice choices. The narrative form of the interview broke down interpersonal and interprofessional barriers, creating a new level of trust and respect that could improve professional collaboration. CONCLUSION: This study suggests that life experiences from childhood into later adulthood can and do influence professional choices. PMID- 17872848 TI - Adding "value" to clinical practice guidelines. AB - OBJECTIVE: To determine the degree to which current Canadian clinical practice guidelines (CPGs) for common chronic conditions (ie, diabetes, dyslipidemias, hypertension, and osteoporosis) discuss the importance of patients' values and preferences in therapeutic decision making, and provide quantitative information that would allow for comprehensive shared informed decision making. DESIGN: Retrospective, observational review. MAIN OUTCOME MEASURES: The presence or absence of specific mentions of the importance of incorporating patients' values and preferences into therapeutic decision making; the number and type (relative or absolute) of quantitative descriptions of benefit or harm; the number of interventions for which a means of quantitatively determining the probability that an individual patient will experience an end point without and with implementation of the therapeutic intervention; and the number of descriptions of specific or comparative costs of treatment. RESULTS: Three of 5 CPGs mentioned that patients' values or preferences should influence treatment decisions. None of the CPGs recommended that benefits and harms of therapies be discussed with patients. Of the 63 quantitative mentions of therapeutic effects of interventions, 81%were presented using relative terms and 19% met our criteria for applicability to decision making for individual patients. Two of the 5 CPGs did not enumerate any harms. Three of the 5 CPGs made no mention of cost. CONCLUSION: Five prominent Canadian CPGs paid little attention to the issue of patients' values and preferences in therapeutic decision making, even though these issues are fundamental tenets of evidence-based practice. These 5 CPGs provided limited quantitative information on benefits and harms and therefore could not be used by clinicians to truly involve patients in informed decision making. PMID- 17872849 TI - Papanicolaou smears: to swab or not to swab. AB - OBJECTIVE: To determine whether cleaning the cervix with a cotton swab affects the quality of the conventional Papanicolaou smear. DESIGN: Prospective, single blinded randomized case-control study. SETTING: Two academic family medicine teaching units and 1 community family practice site. PARTICIPANTS: Female patients, 18 to 65 years of age, who presented for a routine Pap smear in the family practice setting were randomized into the Swab Group (n = 300) or the No Swab Group (n = 316). INTERVENTION: Before the Pap smear, the cervix of patients in the Swab Group was wiped with a cotton swab until visibly free of mucus. In the No Swab Group, the cervix was not cleaned with a cotton swab before the Pap smear. MAIN OUTCOME MEASURES: The quality of the conventional Pap smear was determined by the presence or absence of endocervical cells noted on the pathology report. RESULTS: There was no major difference in the quality of the Pap smear in terms of the adequacy of endocervical cells between the Swab and No Swab Group. CONCLUSION: Cleaning the cervix with a cotton swab does not appear to affect the quality of the conventional Pap smear in terms of adequacy of endocervical cells. This implies that the practice of wiping or not wiping the mucus from the cervix before taking the Pap smear can be employed at the discretion of the clinician. PMID- 17872850 TI - Characteristics and practice patterns of international medical graduates: how different are they from those of Canadian-trained physicians? AB - OBJECTIVE: To investigate the personal characteristics and practice patterns of international medical graduates (IMGs) practising in southwestern Ontario and to compare them with the personal characteristics and practice patterns of Canadian trained family physicians practising in the same region. DESIGN: Cross-sectional analysis of data gathered from a census of family physicians. SETTING: Southwestern Ontario. PARTICIPANTS: A total of 685 family physicians. MAIN OUTCOME MEASURES: Characteristics and practice patterns of IMG physicians and Canadian-trained physicians. RESULTS: Among all family physicians practising in southwestern Ontario, 15.3% were IMGs. The IMGs were more likely than Canadian trained medical graduates to be older and to have been in practice longer, and less likely to have completed a family medicine residency or to have been involved in undergraduate or postgraduate teaching. The IMGs were more likely to have practised longer in their current locations and to be in solo practice and accepting new patients, but were less likely to be providing maternity and newborn care. They were also more likely than Canadian-trained medical graduates were to be serving in small towns and rural and isolated communities. CONCLUSION: The personal and practice characteristics of IMG physicians vary somewhat from those of their Canadian-trained colleagues. Policy efforts aimed at increasing and integrating IMG family physicians into the work force need to recognize these differences. Further research is needed before our results can be generalized to physicians practising beyond southwestern Ontario. PMID- 17872851 TI - Top 10 differential diagnoses in family medicine: dyspnea. PMID- 17872852 TI - Computed tomographic screening for lung cancer. PMID- 17872853 TI - Filling the gaps: a divergent community of family physicians. PMID- 17872859 TI - A pound of cure? Avoiding a generational decline in overall health. PMID- 17872860 TI - Prescribing antidepressants to pregnant women: what is a family physician to do? PMID- 17872861 TI - Promoting gender equity in family medicine. PMID- 17872865 TI - Rebuttal: should we avoid beta-agonists for moderate and severe chronic obstructive pulmonary disease? Yes. PMID- 17872866 TI - Rebuttal: should we avoid beta-agonists for moderate and severe chronic obstructive pulmonary disease? No. PMID- 17872869 TI - Vitamin D supplementation. PMID- 17872870 TI - Taking ACE inhibitors during early pregnancy: is it safe? AB - QUESTION: I knew that angiotensin-converting enzyme (ACE) inhibitors were risky to use during late pregnancy because they can cause renal shutdown in the fetus. Recently I heard of a study that claimed first-trimester exposure (when many patients still are unaware of their pregnancies) can also cause major malformations. Is this proven? ANSWER: A recent study did suggest an increased risk of malformations after first-trimester exposure to ACE inhibitors among women treated for hypertension. We believe this study had serious limitations that preclude drawing any conclusions at present. PMID- 17872871 TI - Practice tips. Screening and long-term follow-up of depression in my practice. PMID- 17872872 TI - Pain patch. PMID- 17872873 TI - Fusobacterium: elusive cause of life-threatening septic thromboembolism. PMID- 17872874 TI - End-of-life issues for aboriginal patients: a literature review. AB - OBJECTIVE: To understand some of the cross-cultural issues in providing palliative care to aboriginal patients. SOURCES OF INFORMATION: MEDLINE (1966 to 2005), CINAHL, PsycINFO, Google Scholar, and the Aboriginal Health Collection at the University of Manitoba were searched. Studies were selected based on their focus on both general cross-cultural caregiving and, in particular, end-of-life decision making and treatment. Only 39 relevant articles were found, half of which were opinion pieces by experienced nonaboriginal professionals; 14 were qualitative research projects from nursing and anthropologic perspectives. MAIN MESSAGE: All patients are unique. Some cultural differences might arise when providing palliative care to aboriginal patients, who value individual respect along with family and community. Involvement of family and community members in decision making around end-of-life issues is common. Aboriginal cultures often have different approaches to telling bad news and maintaining hope for patients. Use of interpreters and various communication styles add to the challenge. CONCLUSION: Cultural differences exist between medical caregivers and aboriginal patients. These include different assumptions and expectations about how communication should occur, who should be involved, and the pace of decision making. Aboriginal patients might value indirect communication, use of silence, and sharing information and decision making with family and community members. PMID- 17872875 TI - An approach to interpersonal psychotherapy for postpartum depression: focusing on interpersonal changes. AB - OBJECTIVE: To review the principles of interpersonal psychotherapy (IPT)for the treatment of postpartum depression (PPD). SOURCES OF INFORMATION: Empirical literature, IPT manuals including those adapted for PPD, and the authors' clinical experience. MAIN MESSAGE: Level I evidence supports IPT as a treatment for PPD. Interpersonal psychotherapy is ideally suited because it focuses on the important interpersonal changes and challenges women experience during the postpartum period. It is delivered in 12 sessions and emphasizes interpersonal disputes, role transitions, or bereavement. In this article, we describe the IPT model and therapeutic guidelines for treatment of PPD. CONCLUSION: Postpartum depression is an important public health problem with pervasive effects on mothers, infants, and families. Interpersonal psychotherapy is a relevant and effective treatment for women suffering from PPD because it helps address the many interpersonal stressors that arise during the postpartum period. The principles of IPT can be integrated easily into primary care settings as IPT is pragmatic, specific, problem focused, short-term, and highly effective. PMID- 17872876 TI - Translating learning into practice: lessons from the practice-based small group learning program. AB - PROBLEM ADDRESSED The need for effective and accessible educational approaches by which family physicians can maintain practice competence in the face of an overwhelming amount of medical information. OBJECTIVE OF PROGRAM: The practice based small group (PBSG) learning program encourages practice changes through a process of small-group peer discussion-identifying practice gaps and reviewing clinical approaches in light of evidence. PROGRAM DESCRIPTION: The PBSG uses an interactive educational approach to continuing professional development. In small, self-formed groups within their local communities, family physicians discuss clinical topics using prepared modules that provide sample patient cases and accompanying information that distils the best evidence. Participants are guided by peer facilitators to reflect on the discussion and commit to appropriate practice changes. CONCLUSION: The PBSG has evolved over the past 15 years in response to feedback from members and reflections of the developers. The success of the program is evidenced in effect on clinical practice, a large and increasing number of members, and the growth of interest internationally. PMID- 17872877 TI - Mayhem on the ice: do players' injuries put team staff at risk of injury? AB - OBJECTIVE: To investigate the potential for serious injury and the nature of injuries incurred as team staff or support personnel cross ice surfaces to get to players' benches or to attend to injured players. DESIGN: Hybrid study, case series with survey. MAIN OUTCOME MEASURES: Circumstances and nature of reported injuries. RESULTS: Over 4 seasons, 988 injuries to team staff or support personnel were reported, including 94 concussions, 5 injuries to internal organs, 226 fractures, and 86 separations or dislocations. Most of the injuries were incurred by team staff or support personnel responsible for the welfare of players (managers, trainers, therapists, and emergency medical staff). CONCLUSION: Team staff and support personnel incur serious injuries as a result of falls on the ice. Several preventive strategies can be put in place: changes in rink design, policies restricting access to the ice surface, and encouraging team staff and support personnel who must cross the ice surface to attend to injured players to wear gait-stabilizing devices. PMID- 17872878 TI - Are parents aware that their children are overweight or obese? Do they care? AB - OBJECTIVE: To compare children's actual weight status with their parents' perceptions of their weight status. DESIGN: Cross-sectional study, including a self-administered questionnaire. SETTING: Seven elementary schools in Middlesex London, Ont. PARTICIPANTS: A convenience sample of pupils in grades 4 to 6 and their parents. Of the 770 child-parent pairs targeted, 355 pairs participated in the study. MAIN OUTCOME MEASURES: Children's weight, height, and body mass index (BMI). Parents' perceptions of their children's weight status, family demographics, and parents' self-reported body weight and height. The United States Centers for Disease Control's BMI-for-age references were used to define children's weight status (underweight, overweight, or obese). RESULTS: Response rate was 46%. Children's actual weight status (ie, 29.9% overweight or obese and 1.4% underweight) was different from their parents' perceptions of their weight status (ie, 18.3% overweight or obese and 17.2% slightly underweight or underweight). Factors such as children's sex and ethnicity and mothers' weight influenced parents' ability to recognize their children's weight status. Parents' misperceptions of their children's weight status seemed to be unrelated to their levels of education, their family income, or their children's ages. CONCLUSION: A large proportion of parents did not recognize that their children were overweight or obese. Effective public health strategies to increase parents' awareness of their children's weight status could be the first key steps in an effort to prevent childhood obesity. PMID- 17872879 TI - Short report: Can mouth swabs replace throat swabs? Cross-sectional survey of the effectiveness of rapid streptococcal swabs of the buccal mucosa. PMID- 17872880 TI - Are patients with hyperlipidemia undertreated? Study of patients admitted to hospital with coronary events. AB - OBJECTIVE: To identify patients admitted to hospital with coronary events and to estimate their pre-admission coronary risk, including their lipid levels. Despite the available data and numerous guidelines, evidence indicates that many patients with hyperlipidemia are undertreated and are not achieving target lipid levels. DESIGN: Retrospective chart review. SETTING: Acute care community hospital in Winnipeg, Man. PARTICIPANTS: A total of 153 patients who were diagnosed with acute myocardial infarction, unstable angina, or acute coronary syndrome upon admission. METHOD: Each patient's 10-year risk of developing coronary artery disease was calculated, and his or her risk status was established. Each patient's low-density lipoprotein cholesterol (LDL-C) levels were recorded and categorized based on current Canadian guidelines. RESULTS: Mean age of patients was 67.6 years; 60.8% were male. Patients in the low-risk category had a mean LDL C level of 2.98 mmol/L (95% confidence interval [CI] 2.66 to 3.29), and patients in the moderate-risk category had a mean LDL-C level of 3.01 mmol/L (95% CI 2.74 to 3.28), both significantly lower (P < .05) than the LDL-C target levels for patients in those risk categories according to Canadian guidelines. The mean LDL C level for patients in the very high-risk category, however, was 2.53 mmol/L (95% CI 2.35 to 2.71), above the recommended goal. Almost half the patients (48.3%) in the very high-risk category had LDL-C levels that exceeded the goal. Slightly more than 1 in 3 patients in the very high-risk category was reported to be taking lipid-lowering agents. CONCLUSION: Patients in the community who are at very high risk of having cardiovascular events are undertreated with respect to attaining LDL-C target levels. These findings point to an opportunity to prevent patient morbidity and reduce the number of hospitalizations for cardiovascular events. PMID- 17872881 TI - Top 10 differential diagnoses in family medicine: generalized abdominal pain. PMID- 17872882 TI - St John's wort versus paroxetine for depression. PMID- 17872885 TI - Down and out: How surviving postpartum depression made me a better doctor and a better person. PMID- 17872886 TI - Answering clinical questions: What is the best way to search the Web? PMID- 17872889 TI - Record-keeping in primary care: benefits of an electronic system. PMID- 17872894 TI - Investigating MS2/MS3 matching statistics: a model for coupling consecutive stage mass spectrometry data for increased peptide identification confidence. AB - Improvements in ion trap instrumentation have made n-dimensional mass spectrometry more practical. The overall goal of the study was to describe a model for making use of MS(2) and MS(3) information in mass spectrometry experiments. We present a statistical model for adjusting peptide identification probabilities based on the combined information obtained by coupling peptide assignments of consecutive MS(2) and MS(3) spectra. Using two data sets, a mixture of known proteins and a complex phosphopeptide-enriched sample, we demonstrate an increase in discriminating power of the adjusted probabilities compared with models using MS(2) or MS(3) data only. This work also addresses the overall value of generating MS(3) data as compared with an MS(2)-only approach with a focus on the analysis of phosphopeptide data. PMID- 17872895 TI - DNA damage recognition in the rat zygote following chronic paternal cyclophosphamide exposure. AB - The detrimental effects of preconceptional paternal exposure to the alkylating anticancer agent, cyclophosphamide, include aberrant epigenetic programming, dysregulated zygotic gene activation, and abnormalities in the offspring that are transmitted to the next generation. The adverse developmental consequences of genomic instabilities transmitted via the spermatozoon emphasize the need to elucidate the mechanisms by which the early embryo recognizes DNA damage in the paternal genome. Little information exists on DNA damage detection in the zygote. We assessed the impact of paternal cyclophosphamide exposure on phosphorylated H2AX (gammaH2AX) and poly(ADP-ribose) polymerase-1(PARP-1), biomarkers of DNA damage, to determine the capacity in the rat zygote to recognize genomic damage and initiate a response to DNA lesions. An amplified biphasic gammaH2AX response was triggered in the paternal pronucleus in zygotes sired by drug-treated males; the maternal genome was not affected. PARP-1 immunoreactivity was substantially elevated in both parental genomes, coincident with the second phase of gammaH2AX induction in embryos sired by cyclophosphamide-exposed spermatozoa. Thus, paternal exposure to a DNA damaging agent rapidly activates signals implemental for DNA damage recognition in the zygote. Inefficient repair of DNA lesions may lead to persistent alterations of the histone code and chromatin integrity, resulting in aberrant embryogenesis. We propose that the response of the early embryo to disturbances in spermatozoal genomic integrity plays a vital role in determining its outcome. PMID- 17872896 TI - Flow cytometric analysis of micronuclei in peripheral blood reticulocytes III. An efficient method of monitoring chromosomal damage in the beagle dog. AB - Erythrocyte-based micronucleus tests have traditionally analyzed bone marrow because splenic filtration in most species removes micronucleated cells from peripheral blood. We have evaluated a flow cytometric method for monitoring micronucleated reticulocyte frequencies (%MN-RET) in the peripheral blood of beagle dogs treated with cyclophosphamide (CP) and have found that analysis of micronucleated reticulocytes (MN-RETs) in peripheral blood is a suitable surrogate for bone marrow analysis. The three-color flow cytometric method uses anti-CD71 labeling to identify reticulocytes and Plasmodium berghei-containing erythrocytes as a calibration standard. The spontaneous %MN-RET determined by flow cytometry was 0.31 +/- 0.09% (n = 22) for peripheral blood, compared with 0.38 +/- 0.13% (SD, n = 12) for bone marrow, and 0.27 +/- 0.08% (n = 12) for peripheral blood by microscopic scoring with acridine orange staining. The kinetics of appearance and disappearance of MN-RETs in blood were determined by collecting daily samples after iv treatment with CP. The maximum frequency occurred approximately 48 h after dosing. Frequencies of MN-RETs in peripheral blood at steady state following daily CP treatment were 55-68% of corresponding bone marrow values assessed by microscopy and 55-112% as assessed by flow cytometry. This difference is presumably due to splenic removal, which appears slightly less stringent than that previously reported for CP-treated Sprague Dawley rats. Responses in bone marrow and peripheral blood were highly correlated and similar to or greater than those reported in mice and rats at equitoxic doses. PMID- 17872897 TI - Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique. AB - The need to characterize nanoparticles in solution before assessing the in vitro toxicity is a high priority. Particle size, size distribution, particle morphology, particle composition, surface area, surface chemistry, and particle reactivity in solution are important factors which need to be defined to accurately assess nanoparticle toxicity. Currently, there are no well-defined techniques for characterization of wet nanomaterials in aqueous or biological solutions. Previously reported nanoparticle characterization techniques in aqueous or biological solutions have consisted of the use of ultra-high illumination light microscopy and disc centrifuge sedimentation; however, these techniques are limited by the measurement size range. The current study focuses on characterizing a wide range of nanomaterials using dynamic light scattering (DLS) and transmission electron microscopy, including metals, metal oxides, and carbon-based materials, in water and cell culture media, with and without serum. Cell viability and cell morphology studies were conducted in conjunction with DLS experiments to evaluate toxicological effects from observed agglomeration changes in the presence or absence of serum in cell culture media. Observations of material-specific surface properties were also recorded. It was also necessary to characterize the impact of sonication, which is implemented to aid in particle dispersion and solution mixture. Additionally, a stock solution of nanomaterials used for toxicology studies was analyzed for changes in agglomeration and zeta potential of the material over time. In summary, our results demonstrate that many metal and metal oxide nanomaterials agglomerate in solution and that depending upon the solution particle agglomeration is either agitated or mitigated. Corresponding toxicity data revealed that the addition of serum to cell culture media can, in some cases, have a significant effect on particle toxicity possibly due to changes in agglomeration or surface chemistry. It was also observed that sonication slightly reduces agglomeration and has minimal effect on particle surface charge. Finally, the stock solution experienced significant changes in particle agglomeration and surface charge over time. PMID- 17872898 TI - Dermal absorption of arsenic from soils as measured in the rhesus monkey. AB - Regulatory agencies have relied on dermal absorption data for soluble forms of arsenic as the technical basis for specific absorption values that are used to calculate exposure to arsenic in weathered soil. These evaluations indicate that percutaneous absorption of arsenic from soil ranges from 3.2 to 4.5% of the dermally applied dose, based on studies of arsenic freshly mixed with soil. When this value is incorporated into risk assessments and combined with other assumptions about dermal exposures to soil, the conclusion is often that dermal exposure to arsenic from soil may contribute significantly to overall exposure to arsenic in soil. Prior characterization research has indicated that the solubility of arsenic in soil varies, depending on the provenance of the soil, the source of the arsenic, and the chemical interaction of arsenic with other minerals present within the soil matrix. Weathering produces forms of arsenic that are more tightly bound within the soil and less available for absorption. Our research expands on prior in vivo studies to provide insights into the potential for dermal absorption of arsenic from the more environmentally relevant substrate of soil. Specifically, two soils with very high concentrations of arsenic were evaluated under two levels of skin hydration. One soil, containing 1400 mg/kg arsenic, was collected adjacent to a pesticide production facility in New York. The other soil, containing 1230 mg/kg arsenic, was collected from a residential area with a history of application of arsenical pesticides. Although the results of this research are constrained by the small study size dictated by the selection of an animal research model using monkeys, the statistical power was optimized by using a "crossover" study design, wherein each animal could serve as its own comparison control. No other models (animal or in vitro) were deemed adequate for studying the dermal absorption of soil arsenic. Our results show dermal absorption of soluble arsenic in solution to be 4.8 +/- 5.5%, which is similar to results reported earlier for arsenic in solution (and used by regulatory agencies in recommendations regarding dermal absorption of arsenic). Conversely, absorption following application of arsenic in the soil matrices resulted in mean estimated arsenic absorption of 0.5% or less for all soils, and all individual estimates were less than 1%. More specifically, following application of arsenic-bearing soils to the abdomens of monkeys, urinary arsenic excretion could not be readily distinguished from background. This was true across all five soil-dosing trials, including application of the two dry soils and three trials with wet soil. These findings are consistent with our understanding of the environmental chemistry of arsenic, wherein arsenic can be present in soils in complexed mineral forms. This research addresses an important component involved in estimating the true contribution of percutaneous exposures to arsenic in soil relative to exposures via ingestion. Our findings suggest that dermal absorption of arsenic from soil is truly negligible, and that EPA's current default assumption of 3% dermal absorption of arsenic from soils results in significant overestimates of exposure. PMID- 17872899 TI - Efficacy of adjuvant chemotherapy according to Prion protein expression in patients with estrogen receptor-negative breast cancer. AB - BACKGROUND: Prion protein (PrPc) has been previously reported to be associated with resistance to proapoptotic stimuli. We evaluated whether the expression of PrPc was associated with the resistance to adjuvant chemotherapy in patients with estrogen receptor (ER) -negative breast cancer. PATIENTS AND METHODS: The expression of PrPc by primary tumors was assessed by immunohistochemistry in a series of 756 patients included in two randomized trials that compared anthracycline-based chemotherapy to no chemotherapy. The PrPc expression was correlated with ER expression and the benefit of adjuvant chemotherapy was assessed according to PrPc expression in patients with ER-negative tumors. RESULTS: Immunostaining analysis showed that PrPc was mainly expressed by myoepithelial cells in normal breast tissue. Tissue microarray analysis from 756 breast tumors showed that PrPc was associated with ER-negative breast cancer subsets (P < 0.001). Adjuvant chemotherapy was not associated with a significant risk reduction for death in patients with ER-negative/PrPc-positive disease [adjusted hazard ratio (HR) for death = 0.98, 95% confidence interval (CI) 0.45 2.1, P = 0.95], while it decreased the risk for death (HR = 0.39, 95% CI 0.2 0.74, P = 0.004) in patients with ER-negative/PrPc-negative tumors. CONCLUSION: These data indicate that ER-negative/PrPc-negative phenotype is associated with a high sensitivity to adjuvant chemotherapy. PMID- 17872900 TI - Salvage chemotherapy for metastatic breast cancer: results of a phase II study with bendamustine. AB - BACKGROUND: Bendamustine, a bifunctional alkylating agent with anticipated purin like properties is active in metastatic breast cancer (MBC) patients. This multicenter phase II trial defines the toxicity and activity of bendamustine in heavily pretreated patients. PATIENTS AND METHODS: Fifty-one patients were included. Patients had a median number of 2 prior chemotherapeutic regimens for MBC (range 0-7) consisting of anthracyclines and taxanes: 26 patients (51%); anthracyclines: nine patients (17.6%); taxanes: seven patients (13.7%); others: five patients (9.8%). Bendamustine was administered four weekly at a dose of 120 mg/m(2) on days 1 and 2. RESULTS: Fifty patients were assessable. Of total, 200 courses were administered. We observed no complete response (CR); 10 patients [20%; 95% confidence interval (CI): 10.0% to 33.7%] achieved a partial response (PR), 14 patients (28%) remained stable for at least 6 months resulting in a clinical benefit rate (CR + PR + stable disease) of 48% (95% CI: 33.7%to 52.6%). Median time to progression was 3.4 months (range 1-51.1). The median duration of remission was 6.6 months (range 1.8-48.7). The treatment was well tolerated with mainly hematologic toxic effects. CONCLUSION: Single-agent bendamustine is an active treatment in patients with MBC independent of the previous treatment. The low toxicity profile favors its use as a single agent. PMID- 17872901 TI - HER-2 overexpression/amplification and its interaction with taxane-based therapy in breast cancer. AB - Breast cancer (BC) is the most common cancer in women and it is incurable when metastases are diagnosed. Taxanes, namely docetaxel and paclitaxel, are effective chemotherapeutic agents in the metastatic, neoadjuvant and adjuvant settings. HER 2 overexpression/amplification is detected in 25-30% of BCs and confers aggressive tumor behavior as well as resistance to some systemic treatments; nevertheless, its association with response to taxane-based chemotherapy is still unclear, with conflicting results in both in vitro and in vivo preclinical studies. This review will address the impact of HER-2 overexpression/amplification in BC patients treated with taxanes. Prospective, randomized trials incorporating important biological hypotheses are either ongoing or just closed, and their results will hopefully help to shed more light on this issue. PMID- 17872902 TI - The challenge of biosimilars. AB - BACKGROUND: The purpose of this report was to review issues associated with the introduction of alternative versions of biosimilars used in the oncology setting. DESIGN: Data were obtained by searches of MEDLINE, PubMed, references from relevant English-language articles, and guidelines from the European Medicines Agency. RESULTS: When biosimilars are approved in EU, they will be considered 'comparable' to the reference product, but this does not ensure therapeutic equivalence. Inherent differences between biosimilars may produce dissimilarities in clinical efficacy, safety, and immunogenicity. Switching biosimilars should be considered a change in clinical management. Regulatory guidelines have been established for some biosimilar categories but, because of the limited clinical experience with biosimilars at approval, pharmacovigilance programs will be important to establish clinical databases. Guidelines also provide a mechanism for the extrapolation of clinical indications (approved indications for which the biosimilar has not been studied). This may be of concern where differences in biological activity can result in adverse outcomes or when safety is paramount (e.g. stem cell mobilization in healthy donors). These issues should be addressed in biosimilar labeling. CONCLUSIONS: Biosimilars should provide cost savings and greater accessibility to biopharmaceuticals. A thorough knowledge surrounding biosimilars will ensure the appropriate use of biopharmaceuticals. PMID- 17872904 TI - Heterozygosity of mannose-binding lectin (MBL2) genotypes predicts advantage (heterosis) in relation to fatal outcome in intensive care patients. AB - Polymorphisms in the MBL2 gene, which affect the structure and influence on the serum concentration of mannose-binding lectin (MBL), are associated with inflammatory and infectious conditions. The importance of MBL2 polymorphisms on outcome in critical ill patients is unclear. Five hundred and thirty-two consecutive critically ill patients admitted to an intensive care unit (ICU) were included over a period of 18 months. Five hundred and thirty-three individuals served as controls. Vital status was obtained 15.5 months after the last patient was included. MBL2 polymorphisms were determined by a PCR-based assay. Homozygosity for MBL2 variant alleles (O/O) causing MBL structural defects was associated with the highest adjusted mortality rate followed by homozygosity for the normal MBL2 allele (A/A) encoding high MBL levels, whereas heterozygous A/O patients had the most favourable outcome (P = 0.015). MBL2 alleles were not associated with death in ICU (n = 166, P = 0.7), but the association appeared soon after discharge from ICU (n = 366): hazard ratio (HR) for O/O using A/A as reference was 1.33 (95% CI: 0.8-2.2) and for A/O it was 0.62 (95% CI: 0.4-0.8) respectively (P = 0.0045) at completion. No difference in MBL2 frequency was observed between patients and controls at baseline, and between patients classified as having sepsis or not. However, patients with the MBL2 O/O genotype had an increased frequency of Gram-positive bacterial infection (P = 0.01). Heterozygosity for MBL2 alleles confers a protective effect whereas homozygosity is associated with the worst outcome soon after discharge from ICU. This may be an example of heterosis. PMID- 17872903 TI - Maintaining the dose intensity of ICE chemotherapy with a thrombopoietic agent, PEG-rHuMGDF, may confer a survival advantage in relapsed and refractory aggressive non-Hodgkin lymphoma. AB - INTRODUCTION: HDT/ASCT is standard for relapsed and refractory DLCL patients responding to second-line chemotherapy. We incorporated a thrombopoietic agent into the ICE chemotherapy program to potentially: decrease platelet associated toxicities, augment stem cell collection and maintain dose intensity. METHODS: This randomized, double-blind, placebo-controlled phase I/II trial examines PEG rHuMGDF versus placebo with ICE chemotherapy. Phase I compared three cohorts and defined a clinically effective dose (CED). Phase II evaluated the CED versus placebo. Outcome measures included safety, hematological end-points, stem cell collection and the impact of dose-intensity on outcome. RESULTS: Forty-one patients with primary refractory (16) or relapsed DLCL (25) were treated; Response rates for evaluable patients are: 75% (12/16) for placebo and 82% (18/22) for PEG-rHuMGDF. PEG-rHuMGDF treated patients had significantly less grade IV thrombocytopenia, higher median platelet nadirs, and less platelet transfusion per cycle. ICE dose intensity was improved with PEG-rHuMGDF versus placebo: 75 versus 42% (P = 0.008). At 8.5 years median follow-up, overall and event-free survival are 47 and 31%, respectively. Patients treated on PEG-rHuMGDF versus placebo had improved survival (59 versus 31%, P = 0.06). CONCLUSION: PEG rHuMGDF ameliorated thrombocytopenia, improved platelet recovery, and maintained ICE dose intensity. Potential survival advantages conferred by maintaining dose intensity require validation with newer thrombopoietic agents. PMID- 17872905 TI - Lack of fibulin-3 causes early aging and herniation, but not macular degeneration in mice. AB - A mutation in the EFEMP1 gene causes Malattia Leventinese, an inherited macular degenerative disease with strong similarities to age-related macular degeneration. EFEMP1 encodes fibulin-3, an extracellular matrix protein of unknown function. To investigate its biological role, the murine Efemp1 gene was inactivated through targeted disruption. Efemp1(-/-) mice exhibited reduced reproductivity, and displayed an early onset of aging-associated phenotypes including reduced lifespan, decreased body mass, lordokyphosis, reduced hair growth, and generalized fat, muscle and organ atrophy. However, these mice appeared to have normal wound healing ability. Efemp1(-/-) mice on a C57BL/6 genetic background developed multiple large hernias including inguinal hernias, pelvic prolapse and protrusions of the xiphoid process. In contrast, Efemp1(-/-) mice on a BALB/c background rarely had any forms of hernias, indicating the presence of modifiers for fibulin-3's function in different mouse strains. Histological analysis revealed a marked reduction of elastic fibers in fascia, a thin layer of connective tissue maintaining and protecting structures throughout the body. No apparent macular degeneration associated defects were found in Efemp1(-/-) mice, suggesting that loss of fibulin-3 function is not the mechanism by which the mutation in EFEMP1 causes macular degeneration. These data demonstrate that fibulin-3 plays an important role in maintaining the integrity of fascia connective tissues and regulates aging. PMID- 17872906 TI - Functional expression of M3, a muscarinic acetylcholine receptor subtype, in taste bud cells of mouse fungiform papillae. AB - Taste bud cells (TBCs) express various neurotransmitter receptors assumed to facilitate or modify taste information processing within taste buds. We investigated the functional expression of muscarinic acetylcholine receptor (mAChR) subtypes, M1-M5, in mouse fungiform TBCs. ACh applied to the basolateral membrane of TBCs elevates the intracellular Ca(2+) level in a concentration dependent manner with the 50% effective concentration (EC(50)) of 0.6 microM. The Ca(2+) responses occur in the absence of extracellular Ca(2+) and are inhibited by atropine, a selective antagonist against mAChRs. The order of 50% inhibitory concentration (IC(50)) examined with a series of antagonists selective to mAChR subtypes shows the expression of M3 on TBCs. Perforated whole-cell voltage clamp studies show that 1 microM ACh blocks an outwardly rectifying current and that 100 nM atropine reverses the block. Reverse transcriptase-mediated polymerase chain reaction studies suggest the expression of M3 but not the other mAChR subtypes. Immunohistochemical studies show that phospholipase Cbeta immunoreactive TBCs and synaptosome-associated protein of 25 kDa-immunoreactive nerve endings are immunoreactive to a transporter that packs ACh molecules into synaptic vesicles (vesicular acetylcholine transporter). These results show that M3 occurs on a few fungiform TBCs and suggest that a few nerve endings, and probably a few TBCs, release ACh by exocytosis. The role of ACh in taste responses is discussed. PMID- 17872907 TI - Short report: how often do UK primary care trials face recruitment delays? AB - Recruitment to trials is often viewed as problematic but data are scarce. This study surveyed authors of published primary care trials to assess the scale of recruitment problems. Seventy trial authors were surveyed with a response rate of 56%. Less than one-third of trials recruited to their original timescale. Recruitment requiring GPs to gain patient consent was significantly associated with recruitment problems. The data may be useful in the wider drive to improve recruitment in primary care. PMID- 17872908 TI - Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium. AB - BACKGROUND: Human endometrium has immense regenerative capacity, growing ~5 mm in 7 days every month. We have previously identified a small population of colony forming endometrial stromal cells which we hypothesize are mesenchymal stem cells (MSC). The aim of this study was to determine if the co-expression of two perivascular cell markers, CD146 and platelet-derived growth factor-receptor beta (PDGF-Rbeta), will prospectively isolate endometrial stromal cells which exhibit MSC properties, and determine their location in human endometrium. METHODS: Single cell suspensions of human endometrial stromal cells were fluorescence activated cell sorting (FACS) sorted into CD146(+)PDGF-Rbeta(+) and CD146(-)PDGF Rbeta(-) populations and analysed for colony-forming ability, in vitro differentiation and expression of typical MSC markers. Full thickness human endometrial sections were co-stained for CD146 and PDGF-Rbeta. RESULTS: FACS stromal CD146(+)PDGF-Rbeta(+) stromal cells (1.5% of sorted population) were enriched for colony-forming cells compared with CD146(-)PDGF-Rbeta(-) cells (7.7 +/- 1.7 versus 0.7 +/- 0.2% P <0.0001), and also underwent differentiation into adipogenic, osteogenic, myogenic and chondrogenic lineages. They expressed MSC phenotypic surface markers and were located near blood vessels. CONCLUSION: This study shows that human endometrium contains a small population of MSC-like cells that may be responsible for its cyclical growth, and may provide a readily available source of MSC for tissue engineering applications. PMID- 17872909 TI - Are GnRH antagonists comparable to agonists for use in IVF? AB - We believe that appropriate comparison of optimal GnRH agonist and antagonist regimens has not been performed yet. Currently available meta-analyses included all comparative studies between GnRH agonists and antagonists performed so far, including less than optimal GnRH antagonist regimens. After critical appraisal of the various studied GnRH antagonist regimens in terms of follicular development and IVF outcome, we postulate that early suppression of endogenous FSH results in optimal follicular development. Additionally, stable and early suppression of LH and progesterone levels during the entire period of stimulation may be an advantage for implantation and pregnancy outcome. In this respect, single dose and particularly flexible protocols seem to be less advantageous. Early FSH and LH suppression can be achieved by early GnRH antagonist administration (stimulation day 1) or by oral contraceptive (OC) pretreatment. More studies comparing long GnRH agonist protocols with 'long' GnRH antagonist protocols, with enough power to identify differences in pregnancy rates, are required before appropriate comparison can be made. PMID- 17872910 TI - Histochemical and morphological examination of proliferation and apoptosis in human first trimester villous trophoblast. AB - BACKGROUND: Our present knowledge about trophoblast turnover in human first trimester placental villi based on multiparametric examination of proliferation and apoptosis is limited. METHODS: Human villous placentae collected during 6, 7 and 8 weeks (n = 10/each group) of gestation were examined for trophoblast proliferation and apoptosis based on quantitative analyses of immunopositive Fas, tumor necrosis factor receptor 1 (TNFR1), cytokeratin 18 fragment (18f), number of proliferating cell nuclear antigen (PCNA), Ki67 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) positive nuclei, scores of mitotic and apoptotic indices and ultrastructural characteristics. RESULTS: Mitotic index in cytotrophoblast higher (P < 0.05) at 6 week compared with 7 and 8 weeks of gestation showed significant (P < 0.05) negative correlation between its prevalence and gestational age. Syncytiotrophoblast exhibited higher number of TUNEL positive nuclei (P < 0.01), TUNEL positive apoptotic nuclei (P < 0.05) and apoptotic index (P < 0.05) compared with cytotrophoblast at same gestational age. Positive correlations found between cytokeratin 18f and apoptotic index (P < 0.01), Fas and apoptotic index (P < 0.01), TUNEL positive nuclei and apoptotic index (P < 0.05), cytokeratin 18f and Fas (P < 0.01), whereas cytokeratin 18f (P < 0.05) and Fas (P < 0.05) showed positive correlation only with TUNEL positive apoptotic nuclear data. Phalangeal intrusions of syncytiotrophoblast between transitional cytotrophoblasts showed apposed plasma membranes bearing thickened membrane leaflets, inter-membranous gaps enclosing membranous invaginations, liposome-like particles; patches of membrane seen to be dissolved resulting in cytoplasmic continuity typical of syncytial formation. CONCLUSION: Cellular remodeling of first trimester villous placenta requires a complex homeodynamics involving proliferation in cytotrophoblast, development-associated syncytialization and apoptosis in syncytiotrophoblast. PMID- 17872911 TI - Altered composition of the cumulus-oocyte complex matrix during in vitro maturation of oocytes. AB - BACKGROUND: In vitro maturation (IVM) of mammalian oocytes has potential health benefits for patients undergoing assisted reproduction as an alternative to gonadotrophin treatment. This procedure is also useful for studying the process of oocyte and early embryo development. However, oocytes undergoing IVM have much lower competence than in vivo matured oocytes. Efforts to optimize IVM success have focused on replicating in vivo timing, hormonal milieu and cumulus cell responses associated with maturing oocytes. We have previously identified two extracellular matrix proteins, the protease Adamts1 and hyaluronan-binding proteoglycan Versican, produced by mural granulosa cells that selectively incorporate into the periovulatory cumulus-oocyte complex (COC). METHODS: Murine COC were cultured in the presence of epidermal growth factor and/or FSH. mRNA and protein were measured by real time PCR and Western blot and compared to in vivo derived COC. RESULTS: COCs from mice that underwent IVM for 6 or 20 h in the presence of epidermal growth factor, FSH or in combination had a > 10-fold reduction in mRNA (P < 0.05) for Adamts1 and Vcan when compared with in vivo matured COCs. Hyaluronan synthase 2 expression was up-regulated up to 8-fold (P < 0.05) over the unstimulated control, demonstrating successful induction of cumulus gene expression by the IVM conditions. While in vivo matured COCs showed abundant levels of these proteins, COCs that underwent IVM had neither detectable Adamts1, nor intact or Adamts1-cleaved Vcan. Human cumulus and granulosa cells matured in vivo contained abundant mRNA for Adamts1 and Vcan, demonstrating the potential relevance to human IVM. CONCLUSION: These results indicate that extensively altered COC matrix composition is present during IVM and may contribute to the observed poorer competence of the derived oocytes. PMID- 17872912 TI - Graph-based consensus clustering for class discovery from gene expression data. AB - MOTIVATION: Consensus clustering, also known as cluster ensemble, is one of the important techniques for microarray data analysis, and is particularly useful for class discovery from microarray data. Compared with traditional clustering algorithms, consensus clustering approaches have the ability to integrate multiple partitions from different cluster solutions to improve the robustness, stability, scalability and parallelization of the clustering algorithms. By consensus clustering, one can discover the underlying classes of the samples in gene expression data. RESULTS: In addition to exploring a graph-based consensus clustering (GCC) algorithm to estimate the underlying classes of the samples in microarray data, we also design a new validation index to determine the number of classes in microarray data. To our knowledge, this is the first time in which GCC is applied to class discovery for microarray data. Given a pre specified maximum number of classes (denoted as K(max) in this article), our algorithm can discover the true number of classes for the samples in microarray data according to a new cluster validation index called the Modified Rand Index. Experiments on gene expression data indicate that our new algorithm can (i) outperform most of the existing algorithms, (ii) identify the number of classes correctly in real cancer datasets, and (iii) discover the classes of samples with biological meaning. AVAILABILITY: Matlab source code for the GCC algorithm is available upon request from Zhiwen Yu. PMID- 17872913 TI - EGEETomo: a user-friendly, fault-tolerant and grid-enabled application for 3D reconstruction in electron tomography. AB - Electron tomography is the leading technique to elucidate the structure of complex biological specimens. Due to the resolution needs, huge reconstructions are required. Grid computing has the potential to face the significant computational demands involved. However, there are a number of key issues, such as stability or difficult user-grid interaction, that currently preclude fully exploitation of its potential. EGEETomo is a user-friendly application that facilitates the interaction with the grid for the non-specialized user and automates job submission and supervision. In addition, EGEETomo is supplied with an automated fault recovery mechanism, which is key to make all the work transparent to the user. EGEETomo significantly accelerates tomographic reconstruction by exploiting the computational resources in the EGEE grid with minimal user intervention. AVAILABILITY: http://www.ace.ual.es/~jrbcast/EGEETomo.tar.gz PMID- 17872914 TI - IGG: A tool to integrate GeneChips for genetic studies. AB - To facilitate genetic studies using high-throughput genotyping technologies, we have developed an open source tool to integrate genotype data across the Affymetrix and Illumina platforms. It can efficiently integrate a large amount of data from various GeneChips, add genotypes of the HapMap Project into a specific project, flexibly trim and export the integrated data with different formats of popular genetic analysis tools, and highly control the quality of genotype data. Furthermore, this tool has sufficiently simplified its usage through its user friendly graphic interface and is independent of third-party databases. IGG has successfully been applied to a genome-wide linkage scan in a Charcot-Marie-Tooth disease pedigree by integrating three types of GeneChips and HapMap project genotypes. PMID- 17872915 TI - Log-linear model-based multifactor dimensionality reduction method to detect gene gene interactions. AB - MOTIVATION: The identification and characterization of susceptibility genes that influence the risk of common and complex diseases remains a statistical and computational challenge in genetic association studies. This is partly because the effect of any single genetic variant for a common and complex disease may be dependent on other genetic variants (gene-gene interaction) and environmental factors (gene-environment interaction). To address this problem, the multifactor dimensionality reduction (MDR) method has been proposed by Ritchie et al. to detect gene-gene interactions or gene-environment interactions. The MDR method identifies polymorphism combinations associated with the common and complex multifactorial diseases by collapsing high-dimensional genetic factors into a single dimension. That is, the MDR method classifies the combination of multilocus genotypes into high-risk and low-risk groups based on a comparison of the ratios of the numbers of cases and controls. When a high-order interaction model is considered with multi-dimensional factors, however, there may be many sparse or empty cells in the contingency tables. The MDR method cannot classify an empty cell as high risk or low risk and leaves it as undetermined. RESULTS: In this article, we propose the log-linear model-based multifactor dimensionality reduction (LM MDR) method to improve the MDR in classifying sparse or empty cells. The LM MDR method estimates frequencies for empty cells from a parsimonious log-linear model so that they can be assigned to high-and low-risk groups. In addition, LM MDR includes MDR as a special case when the saturated log linear model is fitted. Simulation studies show that the LM MDR method has greater power and smaller error rates than the MDR method. The LM MDR method is also compared with the MDR method using as an example sporadic Alzheimer's disease. PMID- 17872916 TI - Diabetes and the endocrine heart. PMID- 17872917 TI - Minocycline inhibits West Nile virus replication and apoptosis in human neuronal cells. AB - OBJECTIVES: West Nile virus (WNV) infection causes severe meningitis and encephalitis in a subset of patients. WNV-induced apoptosis has been suggested to contribute to WNV pathogenesis. Tetracyclines exert antiviral effects against HIV and inhibit apoptosis in different models of neuronal disease. Here, the effects of the tetracyclines minocycline, demeclocycline and chlortetracycline were observed on WNV replication and WNV-induced apoptosis in different human CNS derived cell types (primary human brain neurons, primary human retinal pigment epithelial cells and T98G human glioma cell line). METHODS: WNV replication was studied by cytopathic effects and virus yield reduction assay. Cell viability was examined by MTT assay. Apoptosis was investigated by immunostaining for activated caspase 3 and cleaved poly(ADP-ribose) polymerase. Expression and phosphorylation of cellular proteins were examined by western blot. RESULTS: Minocycline exerted the strongest anti-WNV activity. Non-toxic minocycline concentrations that can be achieved in human tissues significantly reduced WNV titres in all cell types tested. Minocycline inhibited WNV-induced apoptosis and suppressed virus-induced activation of c-Jun N-terminal kinase (JNK) and its target c-jun. The JNK inhibitor L-JNKi exerted similar effects to minocycline. CONCLUSIONS: These data suggest that minocycline-induced inhibition of JNK activation contributes to minocycline-induced inhibition of WNV replication and WNV-induced apoptosis. Minocycline is a clinically available, inexpensive and generally very well tolerated drug. It could be readily evaluated for the treatment of humans with serious WNV infection. PMID- 17872918 TI - Comparative activity of pradofloxacin against anaerobic bacteria isolated from dogs and cats. AB - OBJECTIVES: To compare the intrinsic activity of pradofloxacin, a new fluoroquinolone developed for use in veterinary medicine, with other fluoroquinolones, against anaerobic bacteria isolated from dogs and cats. METHODS: One hundred and forty-one anaerobes were isolated from dogs and cats and comparative MICs of pradofloxacin, marbofloxacin, enrofloxacin, difloxacin and ibafloxacin were determined according to standardized agar dilution methodology. RESULTS: Pradofloxacin exerted the greatest antibacterial activity followed by marbofloxacin, enrofloxacin, difloxacin and ibafloxacin. Based on the distinctly lower MIC(50), MIC(90) and mode MIC values, pradofloxacin exhibited a higher in vitro activity than any of the comparator fluoroquinolones. CONCLUSIONS: Pradofloxacin, a novel third-generation fluoroquinolone, has broad-spectrum anti anaerobe activity and offers utility as single-drug therapy for mixed aerobic/anaerobic infections. PMID- 17872919 TI - The RNAi-mediated silencing of xanthine dehydrogenase impairs growth and fertility and accelerates leaf senescence in transgenic Arabidopsis plants. AB - Xanthine dehydrogenase (XDH) is a ubiquitous enzyme involved in purine metabolism which catalyzes the oxidation of hypoxanthine and xanthine to uric acid. Although the essential role of XDH is well documented in the nitrogen-fixing nodules of leguminous plants, the physiological importance of this enzyme remains uncertain in non-leguminous species such as Arabidopsis. To evaluate the impact of an XDH deficiency on whole-plant physiology and development in Arabidopsis, RNA interference (RNAi) was used to generate transgenic lines of this species in which AtXDH1 and AtXDH2, the two paralogous genes for XDH in this plant, were silenced simultaneously. The nearly complete reduction in the total XDH protein levels caused by this gene silencing resulted in the dramatic overaccumulation of xanthine and a retarded growth phenotype in which fruit development and seed fertility were also affected. A less severe silencing of XDH did not cause these growth abnormalities. The impaired growth phenotype was mimicked by treating wild type plants with the XDH inhibitor allopurinol, and was reversed in the RNAi transgenic lines by exogenous supplementation of uric acid. Inactivation of XDH is also associated with precocious senescence in mature leaves displaying accelerated chlorophyll breakdown and by the early induction of senescence related genes and enzyme markers. In contrast, the XDH protein levels increase with the aging of the wild-type leaves, supporting the physiological relevance of the function of this enzyme in leaf senescence. Our current results thus indicate that XDH functions in various aspects of plant growth and development. PMID- 17872920 TI - Self-incompatibility in Papaver: signalling to trigger PCD in incompatible pollen. AB - Sexual reproduction in higher plants uses pollination, involving interactions between pollen and pistil. Self-incompatibility (SI) prevents self-fertilization, providing an important mechanism to promote outbreeding. SI is controlled by the S-locus; discrimination occurs between incompatible pollen, which is rejected, while compatible pollen can achieve fertilization. In Papaver rhoeas, S proteins encoded by the pistil part of the S-locus interact with incompatible pollen to effect rapid inhibition of tip growth. This self-incompatible interaction triggers a Ca(2+)-dependent signalling cascade. SI-specific events triggered in incompatible pollen include rapid depolymerization of the actin cytoskeleton; phosphorylation of soluble inorganic pyrophosphatases, and activation of a MAPK. It has recently been shown that programmed cell death (PCD) is triggered by SI. This provides a precise mechanism for the specific destruction of 'self' pollen. Recent data providing evidence for SI-induced caspase-3-like protease activity, and the involvement of actin depolymerization and MAPK activation in SI-mediated PCD will be discussed. These studies not only significantly advance our understanding of the mechanisms involved in SI, but also contribute to our understanding of functional links between signalling components and initiation of PCD in a plant cell. Recent data demonstrating SI-mediated modification of soluble inorganic pyrophosphatases are also described. PMID- 17872921 TI - Two members of the Arabidopsis CLC (chloride channel) family, AtCLCe and AtCLCf, are associated with thylakoid and Golgi membranes, respectively. AB - Though numerous pieces of evidence point to major physiological roles for anion channels in plants, progress in the understanding of their biological functions is limited by the small number of genes identified so far. Seven chloride channel (CLC) members could be identified in the Arabidopsis genome, amongst which AtCLCe and AtCLCf are both more closely related to bacterial CLCs than the other plant CLCs. It is shown here that AtCLCe is targeted to the thylakoid membranes in chloroplasts and, in agreement with this subcellular localization, that the clce mutants display a phenotype related to photosynthesis activity. The AtCLCf protein is localized in Golgi membranes and functionally complements the yeast gef1 mutant disrupted in the single CLC gene encoding a Golgi-associated protein. PMID- 17872922 TI - Regulation of cytokinin biosynthesis, compartmentalization and translocation. AB - Cytokinins, a group of mobile phytohormones, play an important role in plant growth and development, and their activity is finely controlled by environmental factors in the control of morphogenic and metabolic adaptations. Inorganic nitrogen sources, such as nitrate, are a major factor regulating gene expression of adenosine phosphate-isopentenyltransferase (IPT), a key enzyme of cytokinin biosynthesis. Modulation of IPT and macronutrient transporter gene expression in response to nitrate, sulphate and phosphate, and cytokinin-dependent repression of the transporter genes suggest that cytokinins play a critical role in balancing acquisition and distribution of macronutrients. Biased distribution of trans-zeatin (tZ)-type cytokinins in xylem and N(6)-(Delta(2)-isopentenyl)adenine (iP)-type cytokinins in phloem saps suggest that, in addition to acting as local signals, cytokinins communicate acropetal and systemic long-distance signals, and that structural side chain variations mediate different biological messages. The compartmentalization of tZ- and iP-type cytokinins implies the involvement of a selective transport system. Recent studies have raised the possibility of subsets of the purine permease family as a transporter of cytokinin nucleobases and equilibrative nucleoside transporters (ENT) for cytokinin nucleosides. These biochemical and transgenic data suggest that AtENT6, an Arabidopsis ENT, could also participate in cytokinin nucleoside transport with a preference for iP riboside in vascular tissue. PMID- 17872923 TI - Assessment of the internal dose of 241Am in bone by in vivo measurements of activity deposited in knee. AB - In case of chronic exposure or long time after an acute intake of (241)Am as a consequence of an incident, the assessment of internal dose might be realised by estimating the total activity content of this element in the skeleton. For this purpose, a new methodology has been developed at the Whole Body Counting Laboratory of CIEMAT. In vivo measurements of this bone-seeker radionuclide in the knee are performed using four low energy germanium detectors inside a shielded room. The sensitivity study of this technique resulted in a minimum detectable activity of 7 Bq, for a counting time of 1800 s. Extrapolation to the total activity in the bone has been carried out by taking into account that the bone content of the knee calibration phantom is equivalent to 10.7% of the whole skeleton mass. The results of in vivo measurements of population and the procedure for internal dose evaluation are presented here. PMID- 17872924 TI - Radiation doses from some [3H]-labelled organic compounds following ingestion. AB - Published information, especially human data, on the biokinetics of 11 compounds labelled with 3H was used to develop simple, cautious compound-specific models and to calculate both tissue absorbed doses and effective doses using the OLINDA computer code. The compounds were [3H]-cortisol, 3alpha-Hydroxy-5beta-pregnane 11, 20-dione-7-[3H], cyclic 20 trimethylene acetal, [3H]-ifetroban, [3H]-digoxin, 7-[2'-alpha-methylphenylethylamino[3H]]theophylline, 7-[2'-alpha methylphenylethylamino]theophylline-[3H], [3H]-amphetamine, [17(3)H]-nicergoline, [3H]-colestipol, [3H]-5(S)-benzamido-4-oxo-6-phenylhexanoyl-l-proline and [6 (3)H]-thymidine. The calculated effective doses ranged from 6 to 87% of that predicted by the ICRP default model for uncharacterised organic compounds of tritium (OBTM). For all the compounds studied, the retention of 3H in the body was less than that predicted by the OBTM and the route of excretion was found to influence both tissue and effective doses. It is concluded that although the ICRP OBT model may underestimate doses for specific compounds by up to an order of magnitude, it can still be applied with caution for prospective radiological protection purposes, but it should not be applied for the interpretation of bioassay data. PMID- 17872925 TI - Differences in the characteristics of induced and spontaneous episodes of ventricular fibrillation. AB - AIMS: The degree of organization of ventricular fibrillation (VF) can be examined in terms of the regularity of the electrical activity within the ventricle. Using electrograms (EGMs) stored within implanted cardioverter defibrillators (ICDs), we examined the hypothesis that the degree of organization, or regularity, was different if the VF was induced by electrical stimulation as opposed to occurring clinically due to ischemia or scar. METHODS AND RESULTS: We compared the statistical characteristics of EGMs recorded by ICDs during spontaneous episodes with those induced during device testing in the laboratory in nine subjects. Regularity of the VF EGM signals was quantified using autocorrelation, Shannon entropy (derived from cycle to cycle activation complexes), and Kolmogorov entropy (derived from eight second long episodes of VF). All three measurements showed a statistically greater degree of regularity for induced VF than in spontaneous episodes. CONCLUSION: Analysis of VF EGMs using these techniques is novel and robust, providing a new way for assessing electrical organization during VF. The clinical significance and utility of differences in VF waveform regularity is unclear at this stage. PMID- 17872926 TI - Developments in medicines for children. PMID- 17872927 TI - Three-dimensional power Doppler sonography in short-term therapy monitoring of rheumatoid synovitis. PMID- 17872928 TI - White matter integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging study. AB - Traumatic brain injury (TBI) is a serious public health problem. Even injuries classified as mild, the most common, can result in persistent neurobehavioural impairment. Diffuse axonal injury is a common finding after TBI, and is presumed to contribute to outcomes, but may not always be apparent using standard neuroimaging. Diffusion tensor imaging (DTI) is a more recent method of assessing axonal integrity in vivo. The primary objective of the current investigation was to characterize white matter integrity utilizing DTI across the spectrum of chronic TBI of all severities. A secondary objective was to examine the relationship between white matter integrity and cognition. Twenty mild, 17 moderate to severe TBI and 18 controls underwent DTI and neuropsychological testing. Fractional anisotropy, axial diffusivity and radial diffusivity were calculated from the DTI data. Fractional anisotropy was the primary measure of white matter integrity. Region of interest analysis included anterior and posterior corona radiata, cortico-spinal tracts, cingulum fibre bundles, external capsule, forceps minor and major, genu, body and splenium of the corpus callosum, inferior fronto-occipital fasciculus, superior longitudinal fasciculus and sagittal stratum. Cognitive domain scores were calculated from executive, attention and memory testing. Decreased fractional anisotropy was found in all 13 regions of interest for the moderate to severe TBI group, but only in the cortico spinal tract, sagittal stratum and superior longitudinal fasciculus for the mild TBI group. White Matter Load (a measure of the total number of regions with reduced FA) was negatively correlated with all cognitive domains. Analysis of radial and axial diffusivity values suggested that all severities of TBI can result in a degree of axonal damage, while irreversible myelin damage was only apparent for moderate to severe TBI. The present data emphasize that white matter changes exist on a spectrum, including mild TBI. An index of global white matter neuropathology (White Matter Load) was related to cognitive function, such that greater white matter pathology predicted greater cognitive deficits. Mechanistically, mild TBI white matter changes may be primarily due to axonal damage as opposed to myelin damage. The more severe injuries impact both. DTI provides an objective means for determining the relationship of cognitive deficits to TBI, even in cases where the injury was sustained years prior to the evaluation. PMID- 17872929 TI - Disorders of cognitive and affective development in cerebellar malformations. AB - Acquired cerebellar lesions in adults and children can lead to the development of a complex behavioural pattern termed 'Cerebellar Cognitive Affective Syndrome' (Schmahmann and Sherman, Brain, 1998; 121: 561-79), which is characterized by reduced cognitive efficiency associated with specific neuropsychological deficits (executive and visuospatial disorders), expressive language disorders (mild agrammatism and anomia) and affective disorders with blunting of affect. It is not known whether a symptomatological picture such as this can also be found in congenital cerebellar malformations. We studied the behavioural developmental profile of 27 patients including children and adults with congenital malformations confined to the cerebellum, the largest studied sample to date. Extensive clinical and neuropsychological investigations highlight the presence of a wide range of disorders supporting the important role played by the cerebellum in the acquisition of higher-order cognitive and affective skills. The type and extent of cerebral reorganization processes in the presence of malformative lesions are difficult to predict and may possibly account for the variability of clinical phenotypes. It is, therefore, more difficult to identify a syndromic picture defined as exactly as is the case with acquired lesions. However, the pattern of deficits that we document is in remarkable agreement with the general profile of the Cerebellar Cognitive Affective Syndrome. Malformations affecting the cerebellar vermis induce affective and social disorders and evolve towards more unfavourable pictures often associated with an autistic symptomatology. Malformations of cerebellar hemispheres are more frequently associated with selective neuropsychological deficits involving mainly executive functions and visuospatial and linguistic abilities. Motor deficits are generally less severe, and tend to improve slowly and progressively, in some cases reaching almost complete functionality. Finally, the overall favourable evolution with an onset of skills in advanced age in a consistent subset of subjects suggests that individual follow-ups should be performed in order to monitor the quality and stability of impairments and acquired abilities over time. PMID- 17872930 TI - Effects of unilateral repetitive transcranial magnetic stimulation of the motor cortex on chronic widespread pain in fibromyalgia. AB - Non-invasive unilateral repetitive transcranial magnetic stimulation (rTMS) of the motor cortex induces analgesic effects in focal chronic pain syndromes, probably by modifying central pain modulatory systems. Neuroimaging studies have shown bilateral activation of a large number of structures, including some of those involved in pain processing, suggesting that such stimulation may induce generalized analgesic effects. The goal of this study was to assess the effects of unilateral rTMS of the motor cortex on chronic widespread pain in patients with fibromyalgia. Thirty patients with fibromyalgia syndrome (age: 52.6 +/- 7.9) were randomly assigned, in a double-blind fashion, to two groups, one receiving active rTMS (n = 15) and the other sham stimulation (n = 15), applied to the left primary motor cortex in 10 daily sessions. The primary outcome measure was self reported average pain intensity over the last 24 h, measured at baseline, daily during the stimulation period and then 15, 30 and 60 days after the first stimulation. Other outcome measures included: sensory and affective pain scores for the McGill pain Questionnaire, quality of life (assessed with the pain interference items of the Brief Pain Inventory and the Fibromyalgia Impact Questionnaire), mood and anxiety (assessed with the Hamilton Depression Rating Scale, the Beck Depression Inventory and the Hospital Anxiety and Depression Scale). We also assessed the effects of rTMS on the pressure pain threshold at tender points ipsi- and contralateral to stimulation. Follow-up data were obtained for all the patients on days 15 and 30 and for 26 patients (13 in each treatment group) on day 60. Active rTMS significantly reduced pain and improved several aspects of quality of life (including fatigue, morning tiredness, general activity, walking and sleep) for up to 2 weeks after treatment had ended. The analgesic effects were observed from the fifth stimulation onwards and were not related to changes in mood or anxiety. The effects of rTMS were more long-lasting for affective than for sensory pain, suggesting differential effects on brain structures involved in pain perception. Only few minor and transient side effects were reported during the stimulation period. Our data indicate that unilateral rTMS of the motor cortex induces a long-lasting decrease in chronic widespread pain and may therefore constitute an effective alternative analgesic treatment for fibromyalgia. PMID- 17872931 TI - New methods of analysing cost effectiveness. PMID- 17872932 TI - The Wanless review. PMID- 17872933 TI - Remifentanil preconditioning confers delayed cardioprotection in the rat. AB - BACKGROUND: Preconditioning with remifentanil (RPC) provides immediate cardioprotection in rats via all three types of opioid (OP) receptor. This study sought to investigate whether remifentanil also confers delayed cardioprotection via OP receptors. METHODS: Male rats received preconditioning either by ischaemia (IPC; 5 min occlusion, 5 min reperfusion x 3) or with remifentanil (RPC; 1, 5, 10, and 20 microg kg(-1) min(-1), 20 min infusion). After 24 h, all animals were subjected to 30 min occlusion of the left coronary artery and 2 h of reperfusion. Subsequently, the time-course effect of RPC (10 microg kg(-1) min(-1), 20 min infusion) was determined at 12, 16, 24, 32, 36, and 48 h intervals, using the same experimental procedure. The effect of RPC (10 microg kg(-1) min(-1), 20 min infusion) and IPC in the presence of selective OP receptor antagonists was evaluated at the 24 h interval. Infarct size (IS), as a percentage of the area at risk (AAR), was determined. RESULTS: Pre-treatment with remifentanil at 1, 5, 10, and 20 microg kg(-1) min(-1) significantly reduced the IS/AAR at 24 h with the maximum effect at 10 microg kg(-1) min(-1). Remifentanil at 10 microg kg(-1) min( 1) significantly reduced the IS at 12 h [32.5 (sd 9.1)%]; 16 h [26.1 (2.8)%]; 24 h [19.5 (5.0)%]; 32 h [31.2 (9.1)%]; and 36 h [36.4 (9.4)%] after drug administration. The maximal reduction in IS was seen at 24 h and the effect completely disappeared at 48 h [36.4 (9.4)%]. The protective effect of RPC was abolished or significantly attenuated by blockade of any of the three OP receptors with selective antagonists. CONCLUSIONS: Like IPC, remifentanil produces delayed cardioprotection in anaesthetized rats 12-36 h after administration. The protective effect is mediated via all three OP receptors. PMID- 17872934 TI - Evaluation of the revised laryngeal tube suction: the laryngeal tube suction II in 100 patients. AB - BACKGROUND: We prospectively assessed the performance of the laryngeal tube suction mark II (LTS II). METHODS: LTS II was assessed during controlled and spontaneous ventilation during total i.v. anaesthesia. Ventilation adequacy, functional and anatomical positioning and airway seal were evaluated. RESULTS: One hundred healthy patients (30F:70M) aged 18-85-yr-old were studied. Insertion of the LTS II was successful in 71 at first attempt, in 24 at second attempt and in five at third/fourth attempt. Median insertion time was 15 s (range 5-120 s). Temporary obstruction occurred in six patients. A median of one manipulation per patient was required to establish an airway (range 0-5). During maintenance, temporary airway obstruction occurred in eight patients. Use of the device was abandoned once during insertion, once during maintenance and once because of complications unrelated to the study. The airway was clear in 89 of 97 patients during maintenance and partially obstructed in eight. Median seal pressure was 29.5 (range 15-85) cm H2O. A gastric tube was passed via the posterior channel in 97 of 99 patients. The glottis was visible using a fibrescope passed via the device in 51% of patients. Via the drain tube the upper oesophagus was visible in 22% and this was open in 50%. Blood was visible on the device after removal in 12 patients. After the operation 14 patients reported mild sore throat. DISCUSSION: The LTS II appears to be an improvement on its predecessor and merits further investigation comparing it with its competitors during use for anaesthesia and emergency airway management. PMID- 17872935 TI - Sciatica and the sacroiliac joint: a forgotten concept. AB - The definition of sciatica is restricted to the pattern and localization of pain, although much emphasis is given to root compression as causative factor. Other sources of similar pain patterns are generally neglected. Despite absence of obligatory neurological signs in radicular syndromes, a number of patients are subjected to extensive, but redundant screenings. In this report, three patients are presented with presumed radicular pain syndromes, whose symptoms finally could be linked to the sacroiliac (SI) joint either via CT and MRI scans or via pain relief by intra-articular injection with local anaesthetics. Possible mechanisms of SI joint-related pain and difficulties in diagnostic specificity of signs and symptoms are discussed. PMID- 17872936 TI - Effect of the implementation of NICE guidelines for ultrasound guidance on the complication rates associated with central venous catheter placement in patients presenting for routine surgery in a tertiary referral centre. AB - BACKGROUND: The National Institute for Clinical Excellence (NICE) guidelines of 2002 recommended the use of ultrasound (US) for central venous catheterization in order to minimize complications associated with central line placement. An ongoing audit of line placement by anaesthetists in the theatre complex of a tertiary referral centre looked at the associated complication rates. The objective of the study was to compare complication rates pre- and post implementation of NICE guidelines. METHODS: This prospective, single centre audit looked at all patients in whom a central venous catheter was placed for surgery. Complication rates were assessed for procedures that were performed pre- and post implementation of NICE guidelines. In total, 438 patients were identified for the study, and the procedures were performed either by trainee or by consultant anaesthetists. RESULTS: The pre- and post-implementation complication rates were 10.5% (16/152) and 4.6% (13/284), respectively, representing an absolute risk reduction of 5.9% (95% CI 0.5-11.3%). Comparison of those procedures in which US was used when compared with the landmark technique after implementation found a reduction of 6.9% in complications (95% CI 1.4-12.4%). The reduction in complication rates was larger for specialist registrars than for consultants (11.2% vs 1.6%). CONCLUSIONS: The implementation of NICE guidelines has been associated with a significant reduction in complication rates in our tertiary referral centre. In the light of the cross-speciality evidence of US superiority and our results, it is imperative that routine use of US guidance becomes more widespread. PMID- 17872937 TI - Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. AB - BACKGROUND: Qualitative research explores complex phenomena encountered by clinicians, health care providers, policy makers and consumers. Although partial checklists are available, no consolidated reporting framework exists for any type of qualitative design. OBJECTIVE: To develop a checklist for explicit and comprehensive reporting of qualitative studies (in depth interviews and focus groups). METHODS: We performed a comprehensive search in Cochrane and Campbell Protocols, Medline, CINAHL, systematic reviews of qualitative studies, author or reviewer guidelines of major medical journals and reference lists of relevant publications for existing checklists used to assess qualitative studies. Seventy six items from 22 checklists were compiled into a comprehensive list. All items were grouped into three domains: (i) research team and reflexivity, (ii) study design and (iii) data analysis and reporting. Duplicate items and those that were ambiguous, too broadly defined and impractical to assess were removed. RESULTS: Items most frequently included in the checklists related to sampling method, setting for data collection, method of data collection, respondent validation of findings, method of recording data, description of the derivation of themes and inclusion of supporting quotations. We grouped all items into three domains: (i) research team and reflexivity, (ii) study design and (iii) data analysis and reporting. CONCLUSIONS: The criteria included in COREQ, a 32-item checklist, can help researchers to report important aspects of the research team, study methods, context of the study, findings, analysis and interpretations. PMID- 17872938 TI - Evidence of a non-linear influence of patient age on satisfaction with hospital care. AB - BACKGROUND: Patient age is the main socio-demographic factor influencing patient satisfaction with care but the nature of the relationship between age and patient satisfaction is controversial. OBJECTIVE: This study aims to clarify whether the association of age with satisfaction is linear or shows some other configuration. METHODS: Data were obtained from two different satisfaction studies conducted in 27 short-stay teaching hospitals. Study 1 included 1547 inpatients, who completed the EQS-H questionnaire at the time of discharge. Study 2 included 7624 inpatients interviewed by phone at home after discharge, who answered the SAPHORA questionnaire. On the basis of the results of the exploratory analysis, three models for adjustment of age on satisfaction were compared: a simple linear model, a five-group step function and a linear model with a change in slope. RESULTS: The most suitable model for adjusting patient age to satisfaction scores for quality of medical and nursing care, whether for the EQS-H or the SAPHORA scale, was not a linear relationship: patient age was linearly and positively correlated to satisfaction before 65 years and negatively thereafter. Adjustment of patient age to accommodation and premises satisfaction scores proved to be different, closer to a linear relationship. CONCLUSION: These results suggest considering the patient age variable as a non-linear factor for adjusting satisfaction scores, in particular in relation to care. Further studies are needed to confirm the evidence of a threshold around 65 years beyond which satisfaction scores for the quality of medical and nursing care decrease. PMID- 17872939 TI - Prognostic factors in paediatric acute liver failure. AB - OBJECTIVES: To study the aetiology, outcome and prognostic indicators in children with acute liver failure (ALF). STUDY DESIGN: Retrospective chart review of 210 patients (107 males/103 females; median age: 5.33 years, range: 1-17.4). Patients were followed until discharge (group 1), death (group 2) or liver transplantation (LT; group 3). Data from group 1 were compared to data from the other two groups and King's College criteria were also assessed. RESULTS: Final diagnoses were: 128 (61%) hepatitis A, 68 (32%) indeterminate and 14 (7%) others. The characteristics of patients who survived (n = 59), died (n = 61) and underwent LT (n = 90) were analysed. In multivariate analysis, prothrombin time and encephalopathy III/IV were the most significant parameters suggesting a high likelihood of death. When King's College criteria were applied on admission in patients with and without transplantation, the positive predictive values were 96% and 95%, and the negative predictive values were 82% and 82%, respectively. CONCLUSIONS: Hepatitis A is the main cause of ALF in children in Argentina. Advanced encephalopathy and prolonged prothrombin time were significantly associated with death or need for LT. King's College criteria for predicting the outcome of ALF are applicable in children, including those with ALF due to hepatitis A infection. PMID- 17872940 TI - Overtreatment in threshold and developed countries. AB - In acute paediatrics, overtreatment and overdiagnosis is encountered in threshold and developed countries. The reason for overtreatment may be similar in the two settings, namely the mere availability of invasive procedures, which may lead to their inappropriate use. Physiological healing processes should be integrated into treatment plans and whenever possible natural organ function should be maintained (eg, enteral instead of parenteral nutrition). Standards and guidelines may assist the paediatrician in weighing up the benefits and risks of available invasive diagnostic and therapeutic procedures. Safe and simple methods, successfully introduced in countries with limited resources, are equally useful in the industrialised world, as they have the potential to reduce the application of risky invasive therapies. PMID- 17872941 TI - Impact of hemoglobin on plasma pro-B-type natriuretic peptide concentrations in the general population. AB - BACKGROUND: Age, sex, and renal function contribute to variations in plasma concentrations of B-type natriuretic peptide (BNP) and its molecular precursor (proBNP). Recent studies indicate that anemia may also affect proBNP concentrations in patients with heart failure or stroke. However, the impact of hemoglobin status on proBNP concentrations has not been established in the general population. METHODS: In the 4th examination in the Copenhagen City Heart Study, we performed a nested case-control study of 6238 individuals from a Danish general population. Of these, 3497 randomly selected participants also underwent an echocardiographic examination. The population was stratified into groups depending on health and hemoglobin status. Correlations between hemoglobin and proBNP concentrations were examined by simple and multiple regression analyses, adjusted for variables known to influence the proBNP plasma concentration. RESULTS: The mean proBNP concentration was increased 1.7-fold in the group with anemia vs the nonanemic group [mean (SD) 42 (45) pmol/L vs 25 (29) pmol/L, P <0.0001, n = 5892]. Multiple regression analysis confirmed an independent effect of hemoglobin on proBNP concentrations. In a selected subgroup without signs or symptoms of heart disease (n = 2855), lower hemoglobin concentrations, defined as <120 g/L in women and <130 g/L in men, were associated with increased circulating proBNP concentrations, but the contribution to the overall variation in proBNP concentrations was modest. CONCLUSIONS: Because moderate anemia is associated with a 1.7-fold increase in proBNP concentrations, hemoglobin concentrations should be taken into consideration in patients with nonspecific symptoms of heart disease and increased proBNP concentrations. PMID- 17872942 TI - Effects of body mass index and age on N-terminal pro brain natriuretic peptide are associated with glomerular filtration rate in chronic heart failure patients. AB - BACKGROUND: Obesity is a state characterized by glomerular hyperfiltration and age-related decreases in glomerular filtration rate (GFR). Body mass index (BMI), age, and GFR are associated with plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic heart failure (CHF) patients. We hypothesized that the effects of BMI and age on plasma concentrations of NT proBNP are associated with GFR. METHODS: We obtained clinical data and laboratory test results from 345 CHF patients at the baseline visit in our heart failure clinic and examined the hypothesis using multiple linear regression models. RESULTS: Age (P = 0.0184), BMI (P = 0.0098), hemoglobin (P = 0.0043), heart rhythm (P <0.0001), and left ventricular ejection fraction (P <0.0001) were associated with log(NT-proBNP). After adjustment for GFR estimated by the Cockcroft and Gault equation, the parameter estimates for BMI (P = 0.3807) and age (P = 0.7238) changed markedly and became insignificant. In another model, after adjustment for GFR estimated by the 4-component Modification of Diet in Renal Disease formula (eGFR(MDRD)), the parameter estimates for age (P = 0.0674) changed markedly and became insignificant, but BMI (P = 0.0067) remained significant and unchanged. The eGFR(MDRD) is adjusted for body surface area, which may explain the difference. CONCLUSIONS: In CHF patients, the effect of age on NT-proBNP is associated with estimates for GFR derived from serum creatinine, and the significance of the effects of BMI on NT-proBNP depends on the method by which GFR is estimated. PMID- 17872943 TI - Reduced pepsin A processing of sonic hedgehog in parietal cells precedes gastric atrophy and transformation. AB - Sonic hedgehog (Shh) is not only essential to the development of the gastrointestinal tract, but is also necessary to maintain the characteristic acid secreting phenotype of the adult stomach. Gastrin is the only hormone capable of stimulating gastric acid and is thus required to maintain functional parietal cells. We have shown previously that gastrin-null mice display gastric atrophy and metaplasia prior to progression to distal, intestinal-type gastric cancer. Because reduced levels of Shh peptide correlate with gastric atrophy, we examined whether gastrin regulates Shh expression in parietal cells. We show here that gastrin stimulates Shh gene expression and acid-dependent processing of the 45 kDa Shh precursor to the 19-kDa secreted peptide in primary parietal cell cultures. This cleavage was blocked by the proton pump inhibitor omeprazole and mediated by the acid-activated protease pepsin A. Pepsin A was also the protease responsible for processing Shh in tissue extracts from human stomach. By contrast, extracts prepared from neoplastic gastric mucosa had reduced levels of pepsin A and did not process Shh. Therefore processing of Shh in the normal stomach is hormonally regulated, acid-dependent, and mediated by the aspartic protease pepsin A. Moreover parietal cell atrophy, a known pre-neoplastic lesion, correlates with loss of Shh processing. PMID- 17872944 TI - Specificity of Gbetagamma signaling to Kir3 channels depends on the helical domain of pertussis toxin-sensitive Galpha subunits. AB - Acetylcholine signaling through muscarinic type 2 receptors activates atrial G protein-gated inwardly rectifying K(+) (Kir3) channels via the betagamma subunits of G proteins (Gbetagamma). Different combinations of recombinant Gbetagamma subunits have been shown to activate Kir3 channels in a similar manner. In native systems, however, only Gbetagamma subunits associated with the pertussis toxin sensitive Galpha(i/o) subunits signal to K(+) channels. Additionally, in vitro binding experiments supported the notion that the C terminus of Kir3 channels interacts preferentially with Galpha(i) over Galpha(q). In this study we confirmed in two heterologous expression systems a preference of Galpha(i) over Galpha(q) in the activation of K(+) currents. To identify determinants of Gbetagamma signaling specificity, we first exchanged domains of Galpha(i) and Galpha(q) subunits responsible for receptor coupling selectivity and swapped their receptor coupling partners. Our results established that the G proteins, regardless of the receptor type to which they coupled, conferred specificity to Kir3 activation. We next tested signaling through chimeras between the Galpha(i) and Galpha(q) subunits in which the N terminus, the helical, or the GTPase domains of the Galpha subunits were exchanged. Our results revealed that the helical domain of Galpha(i) (residues 63-175) in the background of Galpha(q) could support Kir3 activation, whereas the reverse chimera could not. Moreover, the helical domain of the Galpha(i) subunit conferred "Galpha(i)-like" binding of the Kir3 C terminus to the Galpha(q) subunits that contained it. These results implicate the helical domain of Galpha(i) proteins as a critical determinant of Gbetagamma signaling specificity. PMID- 17872945 TI - Proper perinuclear localization of the TRIM-like protein myospryn requires its binding partner desmin. AB - Desmin, the muscle-specific intermediate filament protein, surrounds the Z disks and links the entire contractile apparatus to the sarcolemmal cytoskeleton, cytoplasmic organelles, and the nucleus. In an attempt to explore the molecular mechanisms of these associations, we performed a yeast two-hybrid screening of a cardiac cDNA library. We showed that the desmin amino-terminal domain (N-(1-103)) binds to a 413-kDa TRIM-like protein, myospryn, originally identified as the muscle-specific partner of dysbindin, a component of the biogenesis of lysosome related organelles complex 1 (BLOC-1). Binding of desmin with myospryn was confirmed with glutathione S-transferase pulldown assays and coimmunoprecipitation experiments. Western blot analysis revealed that the complex immunoprecipitated by desmin antibodies, in addition to myospryn, contained the BLOC-1 components dysbindin and pallidin. Deletion analysis revealed that only the (N-(1-103)) fragment of desmin binds to myospryn carboxyl terminus and that this association takes place through the 24-amino acid-long carboxyl-terminal end of the SPRY domain of myospryn. Using an antibody against the COOH terminus of myospryn, we demonstrated that myospryn colocalizes with desmin at the periphery of the nucleus, in close proximity to the endoplasmic reticulum, of mouse neonatal cardiomyocytes. In adult heart muscle, the two proteins colocalize, predominantly at intercalated disks and costameres. We also showed that myospryn colocalizes with lysosomes. Using desmin null hearts, we determined that desmin is required for both the proper perinuclear localization of myospryn, as well as the proper positioning of lysosomes, thus suggesting a potential role of desmin intermediate filaments in lysosomes and lysosome-related organelle biogenesis and/or positioning. PMID- 17872946 TI - Identification of SVIP as an endogenous inhibitor of endoplasmic reticulum associated degradation. AB - Misfolded proteins in the endoplasmic reticulum (ER) are eliminated by a process known as ER-associated degradation (ERAD), which starts with misfolded protein recognition, followed by ubiquitination, retrotranslocation to the cytosol, deglycosylation, and targeting to the proteasome for degradation. Actions of multisubunit protein machineries in the ER membrane integrate these steps. We hypothesized that regulation of the multisubunit machinery assembly is a mechanism by which ERAD activity is regulated. To test this hypothesis, we investigated the potential regulatory role of the small p97/VCP-interacting protein (SVIP) on the formation of the ERAD machinery that includes ubiquitin ligase gp78, AAA ATPase p97/VCP, and the putative channel Derlin1. We found that SVIP is anchored to microsomal membrane via myristoylation and co-fractionated with gp78, Derlin1, p97/VCP, and calnexin to the ER. Like gp78, SVIP also physically interacts with p97/VCP and Derlin1. Overexpression of SVIP blocks unassembled CD3delta from association with gp78 and p97/VCP, which is accompanied by decreases in CD3delta ubiquitination and degradation. Silencing SVIP expression markedly enhances the formation of gp78-p97/VCP-Derlin1 complex, which correlates with increased degradation of CD3delta and misfolded Z variant of alpha-1-antitrypsin, established substrates of gp78. These results suggest that SVIP is an endogenous inhibitor of ERAD that acts through regulating the assembly of the gp78-p97/VCP-Derlin1 complex. PMID- 17872947 TI - Stimulus-induced phosphorylation of vacuolar H(+)-ATPase by protein kinase A. AB - Eukaryotic vacuolar-type H(+)-ATPases (V-ATPases) are regulated by the reversible disassembly of the active V(1)V(0) holoenzyme into a cytosolic V(1) complex and a membrane-bound V(0) complex. The signaling cascades that trigger these events in response to changing cellular conditions are largely unknown. We report that the V(1) subunit C of the tobacco hornworm Manduca sexta interacts with protein kinase A and is the only V-ATPase subunit that is phosphorylated by protein kinase A. Subunit C can be phosphorylated as single polypeptide as well as a part of the V(1) complex but not as a part of the V(1)V(0) holoenzyme. Both the phosphorylated and the unphosphorylated form of subunit C are able to reassociate with the V(1) complex from which subunit C had been removed before. Using salivary glands of the blowfly Calliphora vicina in which V-ATPase reassembly and activity is regulated by the neurohormone serotonin via protein kinase A, we show that the membrane-permeable cAMP analog 8-(4-chlorophenylthio)adenosine-3',5' cyclic monophosphate (8-CPT-cAMP) causes phosphorylation of subunit C in a tissue homogenate and that phosphorylation is reduced by incubation with antibodies against subunit C. Similarly, incubation of intact salivary glands with 8-CPT cAMP or serotonin leads to the phosphorylation of subunit C, but this is abolished by H-89, an inhibitor of protein kinase A. These data suggest that subunit C binds to and serves as a substrate for protein kinase A and that this phosphorylation may be a regulatory switch for the formation of the active V(1)V(0) holoenzyme. PMID- 17872948 TI - Identification of a biosynthetic gene cluster in rice for momilactones. AB - Rice diterpenoid phytoalexins such as momilactones and phytocassanes are produced in suspension-cultured rice cells treated with a chitin oligosaccharide elicitor and in rice leaves irradiated with UV light. The common substrate geranylgeranyl diphosphate is converted into diterpene hydrocarbon precursors via a two-step sequential cyclization and then into the bioactive phytoalexins via several oxidation steps. It has been suggested that microsomal cytochrome P-450 monooxygenases (P-450s) are involved in the downstream oxidation of the diterpene hydrocarbons leading to the phytoalexins and that a dehydrogenase is involved in momilactone biosynthesis. However, none of the enzymes involved in the downstream oxidation of the diterpene hydrocarbons have been identified. In this study, we found that a putative dehydrogenase gene (AK103462) and two functionally unknown P-450 genes (CYP99A2 and CYP99A3) form a chitin oligosaccharide elicitor- and UV inducible gene cluster, together with OsKS4 and OsCyc1, the diterpene cyclase genes involved in momilactone biosynthesis. Functional analysis by heterologous expression in Escherichia coli followed by enzyme assays demonstrated that the AK103462 protein catalyzes the conversion of 3beta-hydroxy-9betaH-pimara-7,15 dien-19,6beta-olide into momilactone A. The double knockdown of CYP99A2 and CYP99A3 specifically suppressed the elicitor-inducible production of momilactones, strongly suggesting that CYP99A2, CYP99A3, or both are involved in momilactone biosynthesis. These results provide strong evidence for the presence on chromosome 4 of a gene cluster involved in momilactone biosynthesis. PMID- 17872949 TI - Activated protein C mutant with minimal anticoagulant activity, normal cytoprotective activity, and preservation of thrombin activable fibrinolysis inhibitor-dependent cytoprotective functions. AB - Activated protein C (APC) reduces mortality in severe sepsis patients and exhibits beneficial effects in multiple animal injury models. APC anticoagulant activity involves inactivation of factors Va and VIIIa, whereas APC cytoprotective activities involve the endothelial protein C receptor and protease activated receptor-1 (PAR-1). The relative importance of the anticoagulant activity of APC versus the direct cytoprotective effects of APC on cells for the in vivo benefits is unclear. To distinguish cytoprotective from the anticoagulant activities of APC, a protease domain mutant, 5A-APC (RR229/230AA and KKK191 193AAA), was made and compared with recombinant wild-type (rwt)-APC. This mutant had minimal anticoagulant activity but normal cytoprotective activities that were dependent on endothelial protein C receptor and protease-activated receptor-1. Whereas anticoagulantly active rwt-APC inhibited secondary-extended thrombin generation and concomitant thrombin-dependent activation of thrombin activable fibrinolysis inhibitor (TAFI) in plasma, secondary-extended thrombin generation and the activation of TAFI were essentially unopposed by 5A-APC due to its low anticoagulant activity. Compared with rwt-APC, 5A-APC had minimal profibrinolytic activity and preserved TAFI-mediated anti-inflammatory carboxypeptidase activities toward bradykinin and presumably toward the anaphlatoxins, C3a and C5a, which are well known pathological mediators in sepsis. Thus, genetic engineering can selectively alter the multiple activities of APC and provide APC mutants that retain the beneficial cytoprotective effects of APC while diminishing bleeding risk due to reduction in APC's anticoagulant and APC dependent profibrinolytic activities. PMID- 17872950 TI - Critical and functional regulation of CHOP (C/EBP homologous protein) through the N-terminal portion. AB - C/EBP homologous protein (CHOP) is an endoplasmic reticulum stress-inducible protein that plays a critical role in the regulation of programmed cell death; however, the regulation of its function has not been well characterized. We have previously demonstrated that CHOP is regulated by the ubiquitin-proteasome system. In this study, during the process of clarifying the mechanism of the degradation of CHOP, we identified a novel regulation domain of CHOP in its N terminal portion that is involved in various regulations and functions. The CHOP N-terminal domain is necessary not only for protein degradation but also for its transactivity and interaction with p300. In addition, trichostatin A, a histone deacetylase inhibitor, repressed the degradation of CHOP protein via the N terminal domain. TRB3, a mammalian tribbles homolog that functions as a repressor of CHOP, also interacted with CHOP via the N-terminal portion and significantly blocked the association of p300 with CHOP. These results suggest that the N terminal portion of CHOP plays a crucial role in its functional regulation and enable us to identify a novel function of TRB3 as an intracellular antagonist of the p300-binding domain of CHOP. PMID- 17872951 TI - Approximate analytical time-dependent solutions to describe large-amplitude local calcium transients in the presence of buffers. AB - Local Ca(2+) signaling controls many neuronal functions, which is often achieved through spatial localization of Ca(2+) signals. These nanodomains are formed due to combined effects of Ca(2+) diffusion and binding to the cytoplasmic buffers. In this article we derived simple analytical expressions to describe Ca(2+) diffusion in the presence of mobile and immobile buffers. A nonlinear character of the reaction-diffusion problem was circumvented by introducing a logarithmic approximation of the concentration term. The obtained formulas reproduce free Ca(2+) levels up to 50 microM and their changes in the millisecond range. Derived equations can be useful to predict spatiotemporal profiles of large-amplitude [Ca(2+)] transients, which participate in various physiological processes. PMID- 17872952 TI - Protein folding in membranes: insights from neutron diffraction studies of a membrane beta-sheet oligomer. AB - Studies of the assembly of the hexapeptide Acetyl-Trp-Leu(5) (AcWL(5)) into beta sheets in membranes have provided insights into membrane protein folding. Yet, the exact structure of the oligomer in the lipid bilayer is unknown. Here we use neutron diffraction to study the disposition of the peptides in bilayers. We find that pairs of adjacent deuterium-labeled leucines have no well-defined peak or dip in the transmembrane distribution profiles, indicative of heterogeneity in the depth of membrane insertion. At the same time, the monomeric homolog AcWL(4) exhibits a homogeneous, well-defined, interfacial location in neutron diffraction experiments. Thus, although the bilayer location of monomeric AcWL(4) is determined by hydrophobicity matching or complementarity within the bilayer, the AcWL(5) molecules in the oligomer are positioned at different depths within the bilayer because they assemble into a staggered transmembrane beta-sheet. The AcWL(5) assembly is dominated by protein-protein interactions rather than hydrophobic complementarity. These results have implications for the structure and folding of proteins in their native membrane environment and highlight the importance of the interplay between hydrophobic complementarity and protein protein interactions in determining the structure of membrane proteins. PMID- 17872953 TI - Micro- and macrorheological properties of isotropically cross-linked actin networks. AB - Cells make use of semiflexible biopolymers such as actin or intermediate filaments to control their local viscoelastic response by dynamically adjusting the concentration and type of cross-linking molecules. The microstructure of the resulting networks mainly determines their mechanical properties. It remains an important challenge to relate structural transitions to both the molecular properties of the cross-linking molecules and the mechanical response of the network. This can be achieved best by well defined in vitro model systems in combination with microscopic techniques. Here, we show that with increasing concentrations of the cross-linker heavy meromyosin, a transition in the mechanical network response occurs. At low cross-linker densities the network elasticity is dominated by the entanglement length l(e) of the polymer, whereas at high heavy meromyosin densities the cross-linker distance l(c) determines the elastic behavior. Using microrheology the formation of heterogeneous networks is observed at low cross-linker concentrations. Micro- and macrorheology both report the same transition to a homogeneous cross-linked phase. This transition is set by a constant average cross-linker distance l(c) approximately 15 microm. Thus, the micro- and macromechanical properties of isotropically cross-linked in vitro actin networks are determined by only one intrinsic network parameter. PMID- 17872954 TI - Interaction of spin-labeled inhibitors of the vacuolar H+-ATPase with the transmembrane Vo-sector. AB - The osteoclast variant of the vacuolar H(+)-ATPase (V-ATPase) is a potential therapeutic target for combating the excessive bone resorption that is involved in osteoporosis. The most potent in a series of synthetic inhibitors based on 5 (5,6-dichloro-2-indolyl)-2-methoxy-2,4-pentadienamide (INDOL0) has demonstrated specificity for the osteoclast enzyme, over other V-ATPases. Interaction of two nitroxide spin-labeled derivatives (INDOL6 and INDOL5) with the V-ATPase is studied here by using the transport-active 16-kDa proteolipid analog of subunit c from the hepatopancreas of Nephrops norvegicus, in conjunction with electron paramagnetic resonance (EPR) spectroscopy. Analogous experiments are also performed with vacuolar membranes from Saccharomyces cerevisiae, in which subunit c of the V-ATPase is replaced functionally by the Nephrops 16-kDa proteolipid. The INDOL5 derivative is designed to optimize detection of interaction with the V ATPase by EPR. In membranous preparations of the Nephrops 16-kDa proteolipid, the EPR spectra of INDOL5 contain a motionally restricted component that arises from direct association of the indolyl inhibitor with the transmembrane domain of the proteolipid subunit c. A similar, but considerably smaller, motionally restricted population is detected in the EPR spectra of the INDOL6 derivative in vacuolar membranes, in addition to the larger population from INDOL6 in the fluid bilayer regions of the membrane. The potent classical V-ATPase inhibitor concanamycin A at high concentrations induces motional restriction of INDOL5, which masks the spectral effects of displacement at lower concentrations of concanamycin A. The INDOL6 derivative, which is closest to the parent INDOL0 inhibitor, displays limited subtype specificity for the osteoclast V-ATPase, with an IC(50) in the 10 nanomolar range. PMID- 17872955 TI - The forces applied by cilia depend linearly on their frequency due to constant geometry of the effective stroke. AB - Mucus propelling cilia are excitable by many stimulants, and have been shown to increase their beating frequency up to threefold, by physiological extracellular stimulants, such as adenosine-triphosphate, acetylcholine, and others. This is thought to represent the evolutionary adaptation of mucociliary systems to the need of rapid and efficient cleansing the airways of foreign particles. However, the mucus transport velocity depends not only on the beat frequency of the cilia, but on their beat pattern as well, especially in the case of mucus bearing cilia that beat in a complex, three-dimensional fashion. In this study, we directly measured the force applied by live ciliary tissues with an atomic force microscope, and found that it increases linearly with the beating frequency. This implies that the arc swept by the cilia during their effective stroke remains unchanged during frequency increase, thus leading to a linear dependence of transport velocity on the beat frequency. Combining the atomic force microscope measurements with optical measurements, we have indications that the recovery stroke is performed on a less inclined plane, leading to an effective shortening of the overall path traveled by the cilia tip during this nontransporting phase of their beat pattern. This effect is observed to be independent of the type of stimulant (temperature or chemical), chemical (adenosine-triphosphate or acetylcholine), or concentration (1 microM-100 microM), indicating that this behavior may result from internal details of the cilium mechanical structure. PMID- 17872956 TI - In situ bipolar electroporation for localized cell loading with reporter dyes and investigating gap junctional coupling. AB - Electroporation is generally used to transfect cells in suspension, but the technique can also be applied to load a defined zone of adherent cells with substances that normally do not permeate the plasma membrane. In this case a pulsed high-frequency oscillating electric field is applied over a small two-wire electrode positioned close to the cells. We compared unipolar with bipolar electroporation pulse protocols and found that the latter were ideally suited to efficiently load a narrow longitudinal strip of cells in monolayer cultures. We further explored this property to determine whether electroporation loading was useful to investigate the extent of dye spread between cells coupled by gap junctions, using wild-type and stably transfected C6 glioma cells expressing connexin 32 or 43. Our investigations show that the spatial spread of electroporation-loaded 6-carboxyfluorescein, as quantified by the standard deviation of Gaussian dye spread or the spatial constant of exponential dye spread, was a reliable approach to investigate the degree of cell-cell coupling. The spread of reporter dye between coupled cells was significantly larger with electroporation loading than with scrape loading, a widely used method for dye coupling studies. We conclude that electroporation loading and dye transfer is a robust technique to investigate gap-junctional coupling that combines minimal cell damage with accurate probing of the degree of cell-cell communication. PMID- 17872957 TI - Transport of beads by several kinesin motors. AB - The movements of beads pulled by several kinesin-1 (conventional kinesin) motors are studied both theoretically and experimentally. While the velocity is approximately independent of the number of motors pulling the beads, the walking distance or run-length is strongly increased when more motors are involved. Run length distributions are measured for a wide range of motor concentrations and matched to theoretically calculated distributions using only two global fit parameters. In this way, the maximal number of motors pulling the beads is estimated to vary between two and seven motors for total kinesin concentrations between 0.1 and 2.5 microg/ml or between 0.27 and 6.7 nM. In the same concentration regime, the average number of pulling motors is found to lie between 1.1 and 3.2 motors. PMID- 17872958 TI - Corrections to the Saffman-Delbruck mobility for membrane bound proteins. AB - Recent experiments (Gambin, Y., R. Lopez-Esparza, M. Reffay, E. Sierecki, N. S. Gov, M. Genest, R. S. Hodes, and W. Urbach. 2006. Proc. Natl. Acad. Sci. USA. 103:2098-2102) have called into question the applicability of the Saffman Delbruck diffusivity for proteins embedded in the lipid bilayers. We present a simple argument to account for this observation that should be generically valid for a large class of transmembrane and membrane bound proteins. Whenever the protein-lipid interactions locally deform the membrane, that deformation generates new hydrodynamic stresses on the protein-membrane complex leading to a suppression of its mobility. We show that this suppression depends on the protein size in a manner consistent with the work of Gambin et al. PMID- 17872959 TI - Target-specific and global effectors in gene regulation by MicroRNA. AB - MicroRNAs are responsible for post-transcriptional gene silencing as part of critical cellular pathways and intercellular coordination, for example during embryonic development. Yet, the basic mechanism by which this silencing is accomplished is still not understood. For example, it is not known to what extent and through what process does the suppression of protein accumulation accompany a reduction in mRNA level. Here we present a simple quantitative modeling approach to microRNA mediated silencing. We show how differential responses of the mRNA- and protein levels may be tuned by target-specific parameters and how global effectors may alter this behavior for some-but not all-miRNA targets in the cell. PMID- 17872960 TI - Two-step folding of recombinant mitochondrial porin in detergent. AB - Precise information regarding the transmembrane topology of mitochondrial porin is essential for understanding the mechanisms by which this protein functions. Porin acts as a channel in the outer membrane and interacts with small solutes and proteins to regulate mitochondrial function. The acquisition of high resolution structural data requires a method of maintaining high concentrations of unaggregated, properly folded porin. In the current studies, several mixed detergent systems were analyzed for their ability to fold Neurospora mitochondrial porin expressed in and isolated from Escherichia coli. A mixture of sodium dodecyl sulfate and dodecyl-beta-D-maltopyranoside in a 1:6 molar ratio supports a beta-strand-rich conformation. In this state, the two tryptophan residues in the protein reside in hydrophobic environments, and about half of the nine tyrosines are solvent exposed. Most importantly, heat-labile tertiary contacts, as detected by near-UV circular dichroism spectropolarimetry, in the sodium dodecyl sulfate/dodecyl-beta-D-maltopyranoside-solubilized porin are very similar to those of the protein following functional reconstitution into liposomes. Similarly, both forms are protease resistant. Thus, a method has been identified with the potential to solubilize high concentrations of mitochondrial porin in a state virtually indistinguishable from the membrane-embedded form. PMID- 17872961 TI - Brownian dynamics theory for predicting internal and external blockages of tetraethylammonium in the KcsA potassium channel. AB - The theory of Brownian dynamics is used to model permeation and the blocking of KcsA potassium channels by tetraethylammonium (TEA). A novel Brownian dynamics simulation algorithm is implemented that comprises two free energy profiles; one profile is seen by the potassium ions and the other by the TEA molecules whose shape is approximated by a sphere. Our simulations reveal that internally applied TEA blocks the passage of K(+) ions by physically occluding the pore. A TEA molecule in the external reservoir encounters an attractive energy-well created by four tyrosine residues at position 82, in addition to all other attractive and repulsive forces impinging on it. Using Brownian dynamics, we investigate how deep the energy-well needs to be to reproduce the experimentally determined inhibitory constant k(i) for the TEA blockade of KcsA or the mutant Shaker T449Y. The one-dimensional free energy profile obtained from molecular dynamics is first converted into a one-dimensional potential energy profile, and is then transformed into a three-dimensional free energy profile in Brownian dynamics by adding the short-range potential from the channel walls. When converted, the free energy profile calculated from molecular dynamics gives a well-depth of approximately 10 kT. We systematically alter the depths of the profiles, and then use Brownian dynamics simulations to numerically determine the current versus TEA concentration curves. We show that the sequence of binding and unbinding events of the TEA molecule to the binding pocket can be modeled by a first-order Markov process. The Brownian dynamics simulations also reveal that the probability of a TEA molecule binding to the binding pocket in KcsA potassium channels increases exponentially with TEA concentration and depends also on the applied potential and the K(+) concentration in the simulation assembly. PMID- 17872962 TI - Exploring transferrin-receptor interactions at the single-molecule level. AB - Interaction between the iron transporter protein transferrin (Tf) and its receptor at the cell surface is fundamental for most living organisms. Tf receptor (TfR) binds iron-loaded Tf (holo-Tf) and transports it to endosomes, where acidic pH favors iron release. Iron-free Tf (apo-Tf) is then brought back to the cell surface and dissociates from TfR. Here we investigated the Tf-TfR interaction at the single-molecule level under different conditions encountered during the Tf cycle. An atomic force microscope tip functionalized with holo-Tf or apo-Tf was used to probe TfR. We tested both purified TfR anchored to a mica substrate and in situ TfR at the surface of living cells. Dynamic force measurements showed similar results for TfR on mica or at the cell surface but revealed striking differences between holo-Tf-TfR and apo-Tf-TfR interactions. First, the forces necessary to unbind holo-Tf and TfR are always stronger compared to the apo-Tf-TfR interaction. Second, dissociation of holo-Tf-TfR complex involves overcoming two energy barriers, whereas the apo-Tf-TfR unbinding pathway comprises only one energy barrier. These results agree with a model that proposes differences in the contact points between holo-Tf-TfR and apo-Tf-TfR interactions. PMID- 17872963 TI - Atomic force microscope spectroscopy reveals a hemifusion intermediate during soluble N-ethylmaleimide-sensitive factor-attachment protein receptors-mediated membrane fusion. AB - This study investigated the effect of soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNAREs) on the fusion of egg L-alpha phosphatidylcholine bilayers using atomic force microscope (AFM) spectroscopy. AFM measurements of the fusion force under compression were acquired to reveal the energy landscape of the fusion process. A single main energy barrier governing the fusion process was identified in the absence and presence of SNAREs in the bilayers. Under compression, a significant downward shift in the fusion dynamic force spectrum was observed when cognate v- and t-SNAREs were present in the opposite bilayers. The presence of vesicle-associated membrane protein (VAMP) and binary syntaxin and SNAP 25 in the apposed bilayers resulted in a reduction in the height of the activation potential by approximately 1.3 k(B)T and a >2 fold increase in the width of the energy barrier. The widening of the energy barrier in the presence SNAREs is interpreted as an increase in the compressibility of the membranes, which translates to a greater ease in the bilayer deformation and subsequently the fusion of the membranes under compression. Facilitation of membrane fusion was observed only when SNAREs were present in both bilayers. Moreover, addition of the soluble cytoplasmic domain of VAMP, which interferes with the interaction between opposing v- and t-SNAREs, prevented such facilitation. These observations implicated the interaction between the cytoplasmic domains of opposing SNAREs in the observed fusion facilitation, possibly by destabilizing the bilayers through pulling on their transmembrane segments. Our AFM compression measurements revealed that SNARE mediated membrane fusion proceeded through a sequence of two approximately 5 nm collapses of the membrane, an observation that is consistent with the existence of a hemifused state during the fusion process. PMID- 17872964 TI - Negative charges at protein kinase C sites of troponin I stabilize the inactive state of actin. AB - Alterations in the troponin complex can lead to increases or decreases in contractile activity. Most mutations of troponin that cause hypertrophic cardiomyopathy increase the activity of cardiac muscle fibers. In at least some cases these mutants stabilize the active state of regulated actin. In contrast, phosphorylation of troponin I at residues 43, 45, and 144 inhibits muscle contractility. To determine if alterations of troponin I that reduce activity do stabilize the inactive state of actin, we introduced negative charges at residues 43, 45, and 144 of troponin I to mimic a constitutively phosphorylated state. At saturating calcium, all mutants decreased ATPase rates relative to wild-type actin-tropomyosin-troponin. Reduced activation of ATPase activity was seen with a single mutation at S45E and was not further altered by mutating the other two sites. In the presence of low concentrations of NEM-S1, wild-type troponin was more active than the mutants. At high NEM-S1, the rates of wild-type and mutants approached the same limiting value. Changes in Ca(2+) affinity also support the idea that the equilibrium between states of actin-tropomyosin-troponin was shifted to the inactive state by mutations that mimic troponin I phosphorylation. PMID- 17872965 TI - Neostigmine and pilocarpine attenuated tumour necrosis factor alpha expression and cardiac hypertrophy in the heart with pressure overload. AB - The inflammatory cytokine tumour necrosis factor alpha (TNF alpha) is known to be a major factor contributing to cardiac remodelling and dysfunction. Parasympathetic nervous system cholinergic function can inhibit TNF alpha expression during systemic infection. In the present study, we tested the effects of a cholinesterase inhibitor, neostigmine, and a muscarinic cholinergic agonist, pilocarpine, on cardiac hypertrophy and TNF alpha levels during pressure overload. Rats with transverse aortic constriction exhibited elevated TNF alpha protein levels in the heart, increased heart weight to body weight ratios (an index of cardiac hypertrophy) and decreased left ventricular diastolic function. Two weeks of infusion with neostigmine (6 microg kg(-1) day(-1)) or pilocarpine (0.3 mg kg(-1) day(-1)) significantly reduced cardiac hypertrophy, reduced TNF alpha levels and elevated interleukin-10 levels in heart tissues, and improved ventricular function in rats with transverse aortic constriction. Neither of these treatments significantly changed ventricular pressure load. Furthermore, in primary cultured neonatal cardiac cells, treatment with pilocarpine attenuated adrenergic agonist phenylephrine-induced increased TNF alpha expression and [3H]leucine (a marker of protein synthesis) incorporation in the cells. Collectively, both cholinergic agents decreased TNF alpha levels and attenuated cardiac hypertrophy. Since both agents potentially enhanced cholinergic function, the anti-inflammatory action may be involved in the cardioprotective effect of the treatments with these agents. PMID- 17872966 TI - Epoxygenases and peroxisome proliferator-activated receptors in mammalian vascular biology. AB - Epoxygenases, particularly of the CYP2C and CYP2J families, are important lipid metabolizing enzymes. Epoxygenases are found throughout the cardiovascular system where their lipid products, particularly the epoxyeicosatrienoic acids (EETs), which are arachidonic acid metabolites, have the potential to regulate vascular tone, cellular proliferation, migration, inflammation and cardiac function. The receptors for EETs are, however, poorly understood. The peroxisome proliferator activated receptors (PPARs) are a family of three (alpha, beta/delta and gamma) nuclear receptors that are activated by lipid metabolites. Activation of PPAR alpha and PPAR gamma, similar to the longer term effects of EETs, causes the inhibition of vascular cell proliferation, migration and inflammation. Interestingly, EETs and their metabolites have recently been found to active both PPAR alpha and PPAR gamma. The epoxygenase-EET-PPAR pathway may therefore represent a novel endogenous protective pathway by which short-lived lipid mediators control vascular cell activation. PMID- 17872968 TI - The molecular basis of high-affinity binding of the antiarrhythmic compound vernakalant (RSD1235) to Kv1.5 channels. AB - Vernakalant (RSD1235) is an investigational drug recently shown to convert atrial fibrillation rapidly and safely in patients (J Am Coll Cardiol 44:2355-2361, 2004). Here, the molecular mechanisms of interaction of vernakalant with the inner pore of the Kv1.5 channel are compared with those of the class IC agent flecainide. Initial experiments showed that vernakalant blocks activated channels and vacates the inner vestibule as the channel closes, and thus mutations were made, targeting residues at the base of the selectivity filter and in S6, by drawing on studies of other Kv1.5-selective blocking agents. Block by vernakalant or flecainide of Kv1.5 wild type and mutants was assessed by whole-cell patch clamp experiments in transiently transfected human embryonic kidney 293 cells. The mutational scan identified several highly conserved amino acids, Thr479, Thr480, Ile502, Val505, and Val508, as important residues for affecting block by both compounds. In general, mutations in S6 increased the IC50 for block by vernakalant; I502A caused an extremely local 25-fold decrease in potency. Specific changes in the voltage-dependence of block with I502A supported the crucial role of this position. A homology model of the pore region of Kv1.5 predicted that, of these residues, only Thr479, Thr480, Val505, and Val508 are potentially accessible for direct interaction, and that mutation at additional sites studied may therefore affect block through allosteric mechanisms. For some of the mutations, the direction of changes in IC50 were opposite for vernakalant and flecainide, highlighting differences in the forces that drive drug-channel interactions. PMID- 17872969 TI - Resveratrol (trans-3,5,4'-trihydroxystilbene) ameliorates experimental allergic encephalomyelitis, primarily via induction of apoptosis in T cells involving activation of aryl hydrocarbon receptor and estrogen receptor. AB - Resveratrol (trans-3,5,4'-trihydroxystilbene), a polyphenolic compound found in plant products, including red grapes, exhibits anticancer, antioxidant, and anti inflammatory properties. Using an animal model of multiple sclerosis (MS), we investigated the use of resveratrol for the treatment of autoimmune diseases. We observed that resveratrol treatment decreased the clinical symptoms and inflammatory responses in experimental allergic encephalomyelitis (EAE)-induced mice. Furthermore, we observed significant apoptosis in inflammatory cells in spinal cord of EAE-induced mice treated with resveratrol compared with the control mice. Resveratrol administration also led to significant down-regulation of certain cytokines and chemokines in EAE-induced mice including tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-2, IL-9, IL-12, IL-17, macrophage inflammatory protein-1alpha (MIP-1alpha), monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T-cell expressed and secreted (RANTES), and Eotaxin. In vitro studies on the mechanism of action revealed that resveratrol triggered high levels of apoptosis in activated T cells and to a lesser extent in unactivated T cells. Moreover, resveratrol-induced apoptosis was mediated through activation of aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) and correlated with up-regulation of AhR, Fas, and FasL expression. In addition, resveratrol-induced apoptosis in primary T cells correlated with cleavage of caspase-8, caspase-9, caspase-3, poly(ADP-ribose) polymerase, and release of cytochrome c. Data from the present study demonstrate, for the first time, the ability of resveratrol to trigger apoptosis in activated T cells and its potential use in the treatment of inflammatory and autoimmune diseases including, MS. PMID- 17872970 TI - Adenosine A2A receptor occupancy stimulates collagen expression by hepatic stellate cells via pathways involving protein kinase A, Src, and extracellular signal-regulated kinases 1/2 signaling cascade or p38 mitogen-activated protein kinase signaling pathway. AB - Prior studies indicate that adenosine and the adenosine A2A receptor play a role in hepatic fibrosis by a mechanism that has been proposed to involve direct stimulation of hepatic stellate cells (HSCs). The objective of this study was to determine whether primary hepatic stellate cells produce collagen in response to adenosine (via activation of adenosine A2A receptors) and to further determine the signaling mechanisms involved in adenosine A2A receptor-mediated promotion of collagen production. Cultured primary HSCs increase their collagen production after stimulation of the adenosine A2A receptor in a dose-dependent fashion. Likewise, LX-2 cells, a human HSC line, increases expression of procollagen alphaI and procollagen alphaIII mRNA and their translational proteins, collagen type I and type III, in response to pharmacological stimulation of adenosine A2A receptors. Based on the use of pharmacological inhibitors of signal transduction, adenosine A2A receptor-mediated stimulation of procollagen alphaI mRNA and collagen type I collagen expression were regulated by signal transduction involving protein kinase A, src, and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (erk), but surprisingly, adenosine A2A receptor-mediated stimulation of procollagen alphaIII mRNA and collagen type III protein expression depend on the activation of p38 mitogen-activated protein kinase (MAPK), findings confirmed by small interfering RNA-mediated knockdown of src, erk1, erk2, and p38 MAPK. These results indicate that adenosine A2A receptors signal for increased collagen production by multiple signaling pathways. These results provide strong evidence in support of the hypothesis that adenosine receptors promote hepatic fibrosis, at least in part, via direct stimulation of collagen expression and that signaling for collagen production proceeds via multiple pathways. PMID- 17872971 TI - A highly sensitive, multiplex broad-spectrum PCR-DNA-enzyme immunoassay and reverse hybridization assay for rapid detection and identification of Chlamydia trachomatis serovars. AB - Chlamydia trachomatis (Ct) comprises distinct serogroups and serovars. The present study evaluates a novel Ct amplification, detection, and genotyping method (Ct-DT assay). The Ct-DT amplification step is a multiplex broad-spectrum PCR for the cryptic plasmid and the VD2-region of ompl. The Ct-DT detection step involves a DNA enzyme immunoassay (DEIA) using probes for serogroups (group B, C, and intermediate) and the cryptic plasmid, permitting sensitive detection of 19 Ct serovars (A, B/Ba, C, D/Da, E, F, G/Ga, H, I/Ia, J, K, L1, L2/L2a, and L3) without any cross-reactivity with other Chlamydia species and pathogenic bacteria or commensal organisms of the genital tract. Ct-positive samples are analyzed by a nitrocellulose-based reverse hybridization assay (RHA) containing probes for the 19 different serovars and for the cryptic plasmid. The sensitivity of the PCR DEIA on clinical specimen is equivalent to that of the Cobas TaqMan assay [kappa = 0.95 (95% confidence interval = 0.92 to 0.99)]. Using the RHA, 98% of the Ct-DT detection step-positive samples could be typed. Analysis of cervical swabs from Uganda and The Netherlands revealed that the most common serovars in Uganda are G/Ga (45%), E (21%), K (13%), and F (8%), and in The Netherlands serovars E (38%), F (23%), G/Ga (11%), and D/Da (7%) were most common. Thus, multiplex broad spectrum PCR in combination with DEIA and RHA permits highly sensitive and specific detection and identification of Ct serovars. PMID- 17872972 TI - Expanding the diagnostic capabilities of molecular microbiology by genomic methods. PMID- 17872973 TI - Microparticles of human atherosclerotic plaques enhance the shedding of the tumor necrosis factor-alpha converting enzyme/ADAM17 substrates, tumor necrosis factor and tumor necrosis factor receptor-1. AB - Human atherosclerotic plaques express the metalloprotease tumor necrosis factor (TNF)-alpha converting enzyme (TACE/ADAM-17), which cleaves several transmembrane proteins including TNF and its receptors (TNFR-1 and TNFR-2). Plaques also harbor submicron vesicles (microparticles, MPs) released from plasma membranes after cell activation or apoptosis. We sought to examine whether TACE/ADAM17 is present on human plaque MPs and whether these MPs would affect TNF and TNFR-1 cellular shedding. Flow cytometry analysis detected 12,867 +/- 2007 TACE/ADAM17(+) MPs/mg of plaques isolated from 25 patients undergoing endarterectomy but none in healthy human internal mammary arteries. Plaque MPs harbored mainly mature active TACE/ADAM17 and dose dependently cleaved a pro-TNF mimetic peptide, whereas a preferential TACE/ADAM17 inhibitor (TMI-2) and recombinant TIMP-3 prevented this cleavage. Plaque MPs increased TNF shedding from the human cell line ECV-304 overexpressing TNF (ECV-304(TNF)), as well as TNFR-1 shedding from activated human umbilical vein endothelial cells or ECV-304(TNF) cells, without affecting TNF or TNFR-1 synthesis. MPs also activated the shedding of the endothelial protein C receptor from human umbilical vein endothelial cells. All these effects were inhibited by TMI-2. The present study shows that human plaque MPs carry catalytically active TACE/ADAM17 and significantly enhance the cell surface processing of the TACE/ADAM17 substrates TNF, TNFR-1, and endothelial protein C receptor, suggesting that TACE/ADAM17(+) MPs could regulate the inflammatory balance in the culprit lesion. PMID- 17872974 TI - Plasmin-cleaved beta-2-glycoprotein 1 is an inhibitor of angiogenesis. AB - beta-2-Glycoprotein 1, an abundant plasma glycoprotein, binds anionic cell surfaces and functions as a regulator of thrombosis. Here, we show that cleavage of the kringle domain at Lys317/Thr318 switches its function to a regulator of angiogenesis. In vitro, the cleaved protein specifically inhibited the proliferation and migration of endothelial cells. The protein was without effect on preformed endothelial cell tubes. In vivo, the cleaved protein inhibited neovascularization into subcutaneously implanted Matrigel and Gelfoam sponge implants and the growth of orthotopically injected tumors. Collectively, these data indicate that plasmin-cleaved beta-2-glycoprotein 1 is a potent antiangiogenic and antitumor molecule of potential therapeutic significance. PMID- 17872975 TI - Clusterin associates with altered elastic fibers in human photoaged skin and prevents elastin from ultraviolet-induced aggregation in vitro. AB - Clusterin is a secreted glycoprotein with stress-induced expression in various diseased and aged tissues. It shares basic features with small heat shock proteins because it may stabilize proteins in a folding-competent state. Besides its presence in all human body fluids, clusterin associates with altered extracellular matrix proteins, such as beta-amyloid in Alzheimer senile plaques in the brain. Because dermal connective tissue alterations occur because of aging and UV radiation, we explored the occurrence of clusterin in young, aged, and sun exposed human skin. Immunohistochemical analysis showed that clusterin is constantly associated with altered elastic fibers in aged human skin. Elastotic material of sun-damaged skin (solar elastosis), in particular, revealed a strong staining for clusterin. Because of the striking co-localization of clusterin with abnormal elastic material, we investigated the interaction of clusterin with elastin in vitro. A chaperone assay was established in which elastin was denatured by UV irradiation in the absence or presence of clusterin. This assay demonstrated that clusterin exerted a chaperone-like activity and effectively inhibited UV-induced aggregation of elastin. The interaction of both proteins was further analyzed by electron microscopy, size exclusion chromatography, and mass spectrometry, in which clusterin was found in a stable complex with elastin after UV exposure. PMID- 17872976 TI - Fibroblast growth factor-2 regulates myocardial infarct repair: effects on cell proliferation, scar contraction, and ventricular function. AB - Fibroblast growth factor-2 (FGF2, bFGF) has been proposed to regulate wound healing and angiogenesis, but skin wound healing in FGF2-knockout (FGF2-KO) animals is only slightly delayed. To determine the role of FGF2 in myocardial infarct repair, we studied the evolution of left ventricular geometry, cell proliferation, matrix content, and cardiac function in mice lacking or overexpressing (FGF2-Tg) FGF2. Despite having no effect on initial infarct size, deletion of FGF2 resulted in reduced fibroblast proliferation and interstitial collagen deposition, decreased endothelial proliferation and vascular density, and decreased cardiomyocyte hypertrophy. Furthermore, FGF2-KO mice demonstrated a complete absence of scar contraction, resulting in increased final infarct size and marked increases in chamber size and infarct expansion. These deficits ultimately impaired left ventricular dP/dt compared with wild-type infarcted mice. Conversely, overexpression of FGF2 increased fibroblast proliferation and collagen deposition, accelerated endothelial proliferation, and enhanced cardiomyocyte hypertrophy after infarction. These changes curbed infarct expansion and preserved left ventricular function. Thus, FGF2 is an important regulator of cell proliferation, angiogenesis, collagen synthesis, myocyte hypertrophy, scar contraction, and, ultimately, left ventricular contractile function during infarct repair. FGF2 may be more important in healing of infarcts compared with skin wounds because of the mechanical stress under which infarcts heal. PMID- 17872977 TI - Modeling metabolic effects of the HIV protease inhibitor ritonavir in vitro. PMID- 17872978 TI - Myosin II co-chaperone general cell UNC-45 overexpression is associated with ovarian cancer, rapid proliferation, and motility. AB - Both tumor cell proliferation and metastasis are dependent on myosin II. Because UNC-45 is required to chaperone the assembly of a functional myosin II motor, we examined the expression of the general cell (GC) UNC-45 isoform in ovarian tumors. Serous carcinoma expressed elevated levels of GC UNC-45 compared with normal ovarian surface epithelium and benign cystadenoma. High-stage exhibited greater GC UNC-45 expression than low-stage serous carcinoma. Similarly, GC UNC 45 transcripts and protein levels were higher in ovarian cell lines than in immortalized ovarian surface epithelial cells. Elevation of GC UNC-45 levels by ectopic expression enhanced the rate of ovarian cancer cell proliferation, whereas siRNA knockdown of GC UNC-45 suppressed proliferation without altering myosin II levels. GC UNC-45 and myosin II were diffuse within the cytoplasm of confluent interphase cells, but both accumulated together at the cleavage furrow during cytokinesis. GC UNC-45 and myosin II also trafficked to the leading edges of ovarian cancer cells induced to move in a scratch assay. Knockdown of GC UNC 45 reduced the spreading ability of ovarian cancer cells whereas it was enhanced by GC UNC-45 overexpression. In sum, these findings implicate elevated GC UNC-45 protein expression in ovarian carcinoma proliferation and metastasis. PMID- 17872979 TI - The influence of attention deficits on functional recovery post stroke during the first 12 months after discharge from hospital. AB - BACKGROUND: Attention deficits have been linked to poor recovery after stroke and may predict outcome. We explored the influence of attention on functional recovery post stroke in the first 12 months after discharge from hospital. METHODS: People with stroke completed measures of attention, balance, mobility and activities of daily living (ADL) ability at the point of discharge from hospital, and 6 and 12 months later. We used correlational analysis and stepwise linear regression to explore potential predictors of outcome. RESULTS: We recruited 122 men and women, mean age 70 years. At discharge, 56 (51%) had deficits of divided attention, 45 (37%) of sustained attention, 43 (36%) of auditory selective attention and 41 (37%) had visual selective attention deficits. Attention at discharge correlated with mobility, balance and ADL outcomes 12 months later. After controlling for the level of the outcome at discharge, correlations remained significant in only five of the 12 relationships. Stepwise linear regression revealed that the outcome measured at discharge, days until discharge and number of medications were better predictors of outcome: in no case was an attention variable at discharge selected as a predictor of outcome at 12 months. CONCLUSIONS: Although attention and function correlated significantly, this correlation was reduced after controlling for functional ability at discharge. Furthermore, side of lesion and the attention variables were not demonstrated as important predictors of outcome 12 months later. PMID- 17872980 TI - Fatigue is associated with cerebral white matter hyperintensities in patients with systemic lupus erythematosus. AB - BACKGROUND: Fatigue is a disabling phenomenon in many patients who have systemic lupus erythematosus (SLE). The pathophysiological processes are unknown, and no known biological disease factors influence the phenomenon. Because depressive mood is consistently associated with fatigue, and drug treatment for SLE does not ameliorate fatigue, a psychological explanation could be an alternative. In search of a somatic basis for fatigue, we looked for alternative markers of biologic activity associated with fatigue. Cerebral white matter hyperintensities (WMHs) represent biochemical changes of brain tissue and are frequently encountered in patients with SLE, and are associated with cognitive impairment in patients with multiple sclerosis. Presence of such an association between fatigue and WMHs in SLE would favour a biological axis to fatigue. METHODS: A cross sectional, case-control study with 62 unselected patients with SLE and 62 age- and gender-matched healthy subjects. Fatigue was evaluated using the Fatigue Severity Scale (FSS) and a fatigue visual analogue scale (VAS). WMHs were rated using Scheltens' method. RESULTS: Greater fatigue and more WMHs appeared in patients with SLE versus healthy subjects. In the full group of patients (n = 62), fatigue VAS was associated with total WMH score (p = 0.009). In subgroup analysis of patients without clinical depression (n = 40), the association with total WMH remained (p = 0.035), whereas this was not the case in the depressed group (n = 18) (p = 0.211). CONCLUSION: Increased cerebral WMH load is associated with increased fatigue, indicating a biological origin for some portion of fatigue in patients with SLE. PMID- 17872981 TI - Irregularity distinguishes limb tremor in cervical dystonia from essential tremor. AB - INTRODUCTION: Patients with cervical dystonia (CD) often have limb tremor that is clinically indistinguishable from essential tremor (ET). Whether a common central mechanism underlies the tremor in these conditions is unknown. We addressed this issue by quantifying limb tremor in 19 patients with CD and 35 patients with ET. METHOD: Postural, resting and kinetic tremors were quantified (amplitude, mean frequency and regularity) using a three-axis accelerometer. RESULTS: The amplitude of limb tremor in ET was significantly higher than in CD, but the mean frequency was not significantly different between the groups. The cycle-to-cycle variability of the frequency (ie the tremor irregularity), however, was significantly greater (approximately 50%) in CD. Analysis of covariance excluded the possibility that the increased irregularity was related to the smaller amplitude of tremor in CD (ANCOVA: p = 0.007, F = 5.31). DISCUSSION: We propose that tremor in CD arises from oscillators with different dynamic characteristics, producing a more irregular output, whereas the tremor in ET arises from oscillators with similar dynamic characteristics, producing a more regular output. We suggest that variability of tremor is an important parameter for distinguishing tremor mechanisms. It is possible that changes in membrane kinetics based on the pattern of ion channel expression underlie the differences in tremor in some diseases. PMID- 17872982 TI - First evidence of a pathogenic insertion in the NOTCH3 gene causing CADASIL. PMID- 17872983 TI - Downbeat nystagmus: aetiology and comorbidity in 117 patients. AB - OBJECTIVES: Downbeat nystagmus (DBN) is the most common form of acquired involuntary ocular oscillation overriding fixation. According to previous studies, the cause of DBN is unsolved in up to 44% of cases. We reviewed 117 patients to establish whether analysis of a large collective and improved diagnostic means would reduce the number of cases with "idiopathic DBN" and thus change the aetiological spectrum. METHODS: The medical records of all patients diagnosed with DBN in our Neurological Dizziness Unit between 1992 and 2006 were reviewed. In the final analysis, only those with documented cranial MRI were included. Their workup comprised a detailed history, standardised neurological, neuro-otological and neuro-ophthalmological examination, and further laboratory tests. RESULTS: In 62% (n = 72) of patients the aetiology was identified ("secondary DBN"), the most frequent causes being cerebellar degeneration (n = 23) and cerebellar ischaemia (n = 10). In 38% (n = 45), no cause was found ("idiopathic DBN"). A major finding was the high comorbidity of both idiopathic and secondary DBN with bilateral vestibulopathy (36%) and the association with polyneuropathy and cerebellar ataxia even without cerebellar pathology on MRI. CONCLUSIONS: Idiopathic DBN remains common despite improved diagnostic techniques. Our findings allow the classification of "idiopathic DBN" into three subgroups: "pure" DBN (n = 17); "cerebellar" DBN (ie, DBN plus further cerebellar signs in the absence of cerebellar pathology on MRI; n = 6); and a "syndromatic" form of DBN associated with at least two of the following: bilateral vestibulopathy, cerebellar signs and peripheral neuropathy (n = 16). The latter may be caused by multisystem neurodegeneration. PMID- 17872984 TI - Using the presence of visual hallucinations to differentiate Parkinson's disease from atypical parkinsonism. AB - OBJECTIVES: Visual hallucinations (VH) occur frequently in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) and are much less common in other bradykinetic rigid syndromes. Pathological series suggest that the presence of VH is highly specific for Lewy body pathology. To address the issue of diagnosis in patients with parkinsonism, we developed instructions for a structured interview (Queen Square Visual Hallucination Inventory (QSVHI)), capable of rapidly screening for VH in the outpatient setting. METHODS: 181 consecutive patients from a specialist movement disorders clinic were tested (115 with PD, 23 with progressive supranuclear palsy (PSP), 9 with multiple system atrophy (MSA), 5 with vascular parkinsonism, 19 with unclassifiable parkinsonism (UP) and 8 others), and 15 selected patients from other clinics and 14 neurologically normal controls. The characteristics of hallucinators and non-hallucinators were compared and the sensitivity, specificity and predictive values of VH for a clinical diagnosis of PD calculated. RESULTS: Screening questions identified VH in only 38% of patients with PD. The QSVHI identified VH in 75% of patients with PD and 47% of those with UP. The specificity of VH identified by the QSVHI for PD was 91%, sensitivity was 62%, positive predictive value was 95% and negative predictive value was 48%. CONCLUSIONS: The QSVHI appears to be a sensitive method for identifying VH in a movement disorders clinic. VH occurred predominantly in PD and very rarely in PSP and MSA. Among patients with unclassifiable or undetermined parkinsonism, the presence of VH should be considered a red flag for underlying Lewy body pathology. PMID- 17872985 TI - The contribution of mineral to the material properties of vertebral cartilage from the smooth-hound shark Mustelus californicus. AB - Elasmobranch vertebral cartilage has a substantial mineral fraction (39-55%) and the arrangement of mineral varies among species. We examined vertebrae from one shark species, Mustelus californicus, to determine mineral content, the effect of mineral on material properties and the viscoelastic response of vertebral cartilage. We serially demineralized vertebrae and compressively tested them to failure at varying strain rates. Mineral in vertebral cartilage varies within individuals, intraspecifically and interspecifically; this is in contrast to bone, in which significant variation in mineral content is pathological or an interspecific effect. Within Mustelus, vertebrae with larger mineral fractions were significantly stiffer and stronger; however when variation is assessed across species, the structure has a larger effect. Shark vertebral cartilage did not show a substantial viscoelastic response at biologically relevant strain rates, validating the use of quasistatic testing for this material. PMID- 17872986 TI - Timing is everything: coordination of strike kinematics affects the force exerted by suction feeding fish on attached prey. AB - During aquatic suction feeding, the predator opens its mouth and rapidly expands its buccal cavity, generating a flow field external to the mouth. The rapid expansion of the buccal cavity produces high fluid velocities and accelerations that extend only a short distance from the mouth (about half of one mouth diameter), and only persist for several milliseconds. Therefore, the predator must precisely time its strike to locate the prey within the narrow region of high flow, during the brief period when flow is at its peak. With flow being the agent for transferring force to the prey, the predator may enhance these forces by producing higher water velocities and faster acceleration at the mouth, but also through increasing the strike's accuracy, i.e. locating the prey closer to the mouth at the instant of peak flow speed. The objectives of this study were to directly measure forces exerted by bluegill Lepomis macrochirus on their prey and to determine how bluegill modify force output. Bluegill were offered ghost shrimp tethered to a load cell that recorded force at 5000 Hz, and feeding sequences were synchronously recorded using 500 Hz video. Peak forces exerted on attached 20 mm shrimp ranged from 0.005 N to 0.506 N. In accordance with the short duration of the strikes (average time to peak gape of approximately 13 ms), the forces recorded were brief (approximately 12 ms from initiation to peak force), and force magnitude declined rapidly after peak force. Statistical analysis indicated that rate of buccal expansion, and prey size, but not strike initiation distance, significantly affected peak force. These observed variables were used with results from flow visualization studies to estimate the flow at the prey's location, which allowed the calculation of drag, pressure gradient force and acceleration reaction force. The relationship between these calculated forces and the measured forces was strong, indicating that the model can be used to estimate forces from strike kinematics. This model was then used to study the effects of strike initiation distance on peak force and on the rate of increasing force. Comparisons of model output to empirical results indicated that bluegill time their strike so as to exert an average of approximately 70% of the peak possible force on the prey, and that the observed strike initiation distance corresponded to the distance that maximized modeled force on an attached prey. Our results highlight the ability of bluegill to produce high forces on their prey, and indicate that precision and visual acuity play important roles in prey acquisition, beyond their recognized role in prey detection. PMID- 17872987 TI - Orientation towards prey in antlions: efficient use of wave propagation in sand. AB - Substrate-borne vibration for locating mates, predators and prey is widespread in the animal kingdown. Antlion larvae dig funnel-shaped traps to catch ants and they are totally immersed in dry sand. We used a playback setup reproducing an ant walking on sand to clearly demonstrate that antlions use sand-borne vibrations to locate their prey. Half the tested animals moved towards the stimulus source. The shoot angle of sand tossing was very close to the target angle, indicating excellent ability to perceive stimulus direction. We also discuss orientation mechanisms in sand, a medium with highly unusual wave propagation properties. PMID- 17872988 TI - To what extent might N2 limit dive performance in king penguins? AB - A mathematical model was used to explore if elevated levels of N2, and risk of decompression sickness (DCS), could limit dive performance (duration and depth) in king penguins (Aptenodytes patagonicus). The model allowed prediction of blood and tissue (central circulation, muscle, brain and fat) N2 tensions (P(N2)) based on different cardiac outputs and blood flow distributions. Estimated mixed venous P(N2) agreed with values observed during forced dives in a compression chamber used to validate the assumptions of the model. During bouts of foraging dives, estimated mixed venous and tissue P(N2) increased as the bout progressed. Estimated mean maximum mixed venous P(N2) upon return to the surface after a dive was 4.56+/-0.18 atmospheres absolute (ATA; range: 4.37-4.78 ATA). This is equivalent to N2 levels causing a 50% DCS incidence in terrestrial animals of similar mass. Bout termination events were not associated with extreme mixed venous N2 levels. Fat P(N2) was positively correlated with bout duration and the highest estimated fat P(N2) occurred at the end of a dive bout. The model suggested that short and shallow dives occurring between dive bouts help to reduce supersaturation and thereby DCS risk. Furthermore, adipose tissue could also help reduce DCS risk during the first few dives in a bout by functioning as a sink to buffer extreme levels of N2. PMID- 17872989 TI - Chronic electrical stimulation drives mitochondrial biogenesis in skeletal muscle of a lizard, Varanus exanthematicus. AB - We investigated the capacity for phenotypic plasticity of skeletal muscle from Varanus exanthematicus, the savannah monitor lizard. Iliofibularis muscle from one leg of each lizard was electrically stimulated for 8 weeks. Both stimulated and contralateral control muscles were collected and processed for electron microscopy. We used stereological analysis of muscle cross-sections to quantify the volume densities of contractile elements, sarcoplasmic reticulum, mitochondria and intracellular lipids. We found that mitochondrial volume density was approximately fourfold higher in the stimulated muscle compared to controls, which were similar to previously reported values. Sarcoplasmic reticulum volume density was reduced by an amount similar to the increase in mitochondrial volume density while the volume density of contractile elements remained unchanged. Intracellular lipid accumulation was visibly apparent in many stimulated muscle sections but the volume density of lipids did not reach a significant difference. Although monitor lizards lack the highly developed aerobic metabolism of mammals, they appear to possess the capacity for muscle plasticity. PMID- 17872990 TI - Muscles do more positive than negative work in human locomotion. AB - Muscle work during level walking and ascent and descent ramp and stairway walking was assessed in order to explore the proposition that muscles perform more positive than negative work during these locomotion tasks. Thirty four healthy human adults were tested while maintaining a constant average walking velocity in the five gait conditions. Ground reaction force and sagittal plane kinematic data were obtained during the stance phases of these gaits and used in inverse dynamic analyses to calculate joint torques and powers at the hip, knee and ankle. Muscle work was derived as the area under the joint power vs time curves and was partitioned into positive, negative and net components. Dependent t-tests were used to compare positive and negative work in level walking and net joint work between ascent and descent gaits on the ramp and stairs (P<0.010). Total negative and positive work in level walking was -34 J and 50 J, respectively, with the difference in magnitude being statistically significant (P<0.001). Level walking was therefore performed with 16 J of net positive muscle work per step. The magnitude of the net work in ramp ascent was 25% greater than the magnitude of net work in ramp descent (89 vs -71 J m(-1), P<0.010). Similarly, the magnitude of the net work in stair ascent was 43% greater than the magnitude of net work in stair descent (107 vs -75 J step(-1), P<0.000). We identified three potential causes for the reduced negative vs positive work in these locomotion tasks: (1) the larger magnitude of the accelerations induced by the larger ground reaction forces in descending compared to ascending gaits elicited greater energy dissipation in non-muscular tissues, (2) the ground reaction force vector was directed closer to the joint centers in ramp and stair descent compared to ascent, which reduced the load on the muscular tissues and their energy dissipating response, and (3) despite the need to produce negative muscle work in descending gaits, both ramp and stair descent also had positive muscle work to propel the lower extremity upward and forward into the swing phase movement trajectory. We used these data to formulate two novel hypotheses about human locomotion. First, level walking requires muscles to generate a net positive amount of work per gait cycle to overcome energy losses by other tissues. Second, skeletal muscles generate more mechanical energy in gait tasks that raise the center of mass compared to the mechanical energy they dissipate in gait tasks that lower the center of mass, despite equivalent changes in total mechanical energy. PMID- 17872991 TI - The ontogeny of fin function during routine turns in zebrafish Danio rerio. AB - Zebrafish Danio rerio exhibit spontaneous, routine turns as part of their normal foraging behavior from the early free-swimming stage to adulthood. Given the importance of this behavior and its pervasiveness during zebrafish life history, the functional requirements of routine turning should play an important role in development. Conversely, the ontogeny of turning performance should reflect morphological development. In this paper we analyze the kinematics of routine turning during ontogeny in zebrafish and compare the scaling of turning kinematics to predictions from two existing models. Twenty-nine fish ranging in size from 0.38 to 1.97 cm in fork length (FL) were filmed at 1000 frames s(-1) while performing routine turns. Images were analyzed using image cross correlation to calculate body and fin velocities. We performed piecewise linear regression to identify variables that do not have a constant rate of change across ontogeny and found that two variables, turn angle and angular velocity, have a transition in slope at a body size of approximately 1 cm. Other variables show a constant positive (pectoral and caudal fin velocity, turn duration), negative (body curvature) or zero (head velocity) rate of change across ontogeny. We interpret these trends in light of morphological changes over ontogeny as well as relevant hydrodynamic conditions. We also compare the slope of the log transformed variables to predictions from two scaling models of change in function with increasing size. We find mixed support for both models with no single model being better at predicting a single type of variable such as linear velocities. We conclude that morphological development of the paired and median fins and of the skeleton, is an important factor in determining the performance of routine turning over ontogeny. Three-dimensional kinematics and ecological behavior information will further elucidate the ontogenetic patterns observed here. PMID- 17872992 TI - Nitric oxide formation from nitrite in zebrafish. AB - Nitrite is a potential nitric oxide (NO) donor and may have important biological functions at low concentrations. The present study tests the hypothesis that nitrite accumulation across the gills in fish will cause a massive NO production from nitrite. Zebrafish were exposed to three different nitrite levels for variable time periods, and changes in blood nitrosylhemoglobin (HbNO), methemoglobin (metHb), oxygenated hemoglobin (oxyHb) and deoxygenated hemoglobin (deoxyHb) were evaluated by spectral deconvolution. Blood HbNO (a biomarker of internal NO production) was low in controls, increased to a stable level around 3.7% of total Hb in fish exposed to 0.6 mmol l(-1) nitrite, and to 12.1% (at day 2) in fish exposed to 2 mmol l(-1) nitrite. The very high HbNO levels testify to an extensive conversion of nitrite to NO. With deoxyHb-mediated reduction of nitrite being a major NO-producing mechanism, the data reveal the significance of this mechanism, when hemoglobin cycles between full and intermediate oxygen saturations in the arterial-venous circulation. Fish exposed to 0.6 mmol l(-1) nitrite for up to 5 days could be divided into responding (with elevated metHb) and non-responding individuals. Exposure to 2 mmol l(-1) nitrite caused a time dependent increase in metHb to 59% of total Hb within 2 days. Taking HbNO into account, the functional (potential O2 carrying) Hb was reduced to 29% at this stage. Total blood [Hb] was also significantly decreased. In spite of the reduced blood O2 capacitance, and the possibility that excess NO may inhibit mitochondrial respiration, whole animal routine oxygen consumption was not depressed. PMID- 17872993 TI - Uniform strain in broad muscles: active and passive effects of the twisted tendon of the spotted ratfish Hydrolagus colliei. AB - A muscle's force output depends on the range of lengths over which its fibers operate. Regional variation in fiber shortening during muscle contraction may translate into suboptimal force production if a subset of muscle fibers operates outside the plateau of the length-tension curve. Muscles with broad insertions and substantial shortening are particularly prone to heterogeneous strain patterns since fibers from different regions of the muscle vary in their moment arms, with fibers further from the joint exhibiting greater strains. In the present study, we describe a musculotendon morphology that serves to counteract the variation in moment arm and fiber strains that are inherent in broad muscles. The tendon of the anterior jaw adductor of the spotted ratfish Hydrolagus colliei is twisted such that the distal face of the muscle inserts more proximally than the proximal face. Using quantitative geometric models based on this natural morphology, we show that this inversion of insertion points serves to equalize strains across the muscle such that at any gape angle all fibers in the muscle are operating at similar positions on their length-tension curves. Manipulations of this geometric model show that the natural morphology is ;ideal' compared to other hypothetical morphologies for limiting fiber strain heterogeneity. The uniform strain patterns predicted for this morphology could increase active force production during jaw closing and also decrease passive resistance to jaw opening. This divergence from ;typical' tendon morphology in the jaw adductors of H. colliei may be particularly important given the demands for high force production in durophagy. PMID- 17872994 TI - Is basal metabolic rate influenced by age in a long-lived seabird, the snow petrel? AB - Ageing is associated with a decline in basal metabolic rate (BMR) in many species, including humans. The evolutionary and physiological causes underlying the relationship between age and BMR are poorly understood. Studies of procellariiform seabirds may provide valuable insight because they have a longer maximum lifespan than expected from their body size and rates of energy metabolism. Such studies are rare, however, because there are few populations with a high proportion of individuals of known age. We performed a cross sectional study of energy metabolism in relation to age in a long-lived seabird, the snow petrel Pagodroma nivea. In an Antarctic population that has been subject to a long-term research program, including annual banding of chicks since 1963, we measured BMR of individuals aged between 8 and 39 years. We show that the BMR of the snow petrel does not decrease with increasing age. BMR seems to be sustained at a fixed level throughout the investigated age-span. We review this result in light of the disposable soma theory of ageing, and we discuss whether species-specific relationships between age and basal metabolic rate can be related to differences in maximum lifespan. PMID- 17872995 TI - Rapid assimilation of yolk enhances growth and development of lizard embryos from a cold environment. AB - Selection for rapid growth and development in cold environments results in a geographic pattern known as countergradient variation. The eastern fence lizard, Sceloporus undulatus, exhibits countergradient variation in embryonic growth and development along latitudinal clines. To identify the proximate causes of countergradient variation, we compared the energy budgets of embryos from a cold environment (Virginia) and a warm environment (South Carolina) during development at a realistic thermal cycle. The difference in mean egg size between populations was controlled by removing yolk from large eggs and performing a sham manipulation on other eggs. Respiration was measured every 4 days throughout 48 days of incubation. After this period, eggs were dissected and the energy contents of embryos and yolk were determined by calorimetry. As expected from previous experiments, embryos from Virginia reached a more advanced stage of development and deposited more energy within tissues than embryos from South Carolina. The greater absorption of yolk by embryos from Virginia was associated with a higher rate of respiration. Assimilation of yolk by rapidly growing embryos could reduce growth or survival after hatching. Such costs might explain the maintenance of countergradient variation in S. undulatus. PMID- 17872996 TI - Efficiency of labriform swimming in the bluegill sunfish (Lepomis macrochirus). AB - Bluegill sunfish (Lepomis macrochirus) swim in the labriform mode at low speeds, generating lift and thrust by beating their pectoral fins. The maximal power output available from the two largest pectoral fin adductor and abductor muscles, constituting half of the total pectoral girdle muscle mass, was measured in vitro and used to estimate the muscle mechanical power output during maximal labriform swimming (Pmech; 0.15-0.21 W kg(-1) body mass). Respirometry was used to estimate the total metabolic power input (Ptotal; 0.95 W kg(-1) body mass) and the metabolic power available to the active muscle mass (Pmuscle; Ptotal minus standard metabolic rate, 0.57 W kg(-1) body mass) at this swimming speed. Drag measurements made on towed, dead fish were used to estimate the mechanical power required to overcome body drag (Pdrag; 0.028 W kg(-1) body mass). Efficiency estimates based on these data fell into the following ranges: overall swimming efficiency (etagross=Pmech/Ptotal), 0.16-0.22; muscle efficiency (etamuscle=Pmech/Pmuscle), 0.26-0.37; and propeller efficiency (etaprop=Pdrag/Pmech), 0.15-0.20. Comparison with other studies suggests that labriform swimming may be more efficient than swimming powered by undulations of the body axis. PMID- 17872997 TI - Metabolic and digestive response to food ingestion in a binge-feeding lizard, the Gila monster (Heloderma suspectum). AB - The gastrointestinal tract possesses the capacity to change in form and function in response to fasting and feeding. Such plasticity can be dramatic for species that naturally experience long episodes of fasting between large meals (e.g. sit and-wait foraging snakes, estivating anurans). By contrast, for active foraging species that feed more frequently on smaller meals, gastrointestinal responses are more modest in magnitude. The Gila monster Heloderma suspectum is an active foraging lizard that feeds infrequently on meals weighing up to one-third of its body mass. Additionally, Gila monsters possess a species-specific salivary peptide, exendin-4, which may be involved in the regulation of metabolic and digestive performance. To investigate the adaptive postprandial response of Gila monsters and the potential regulatory role of exendin-4, we measured metabolic and intestinal responses to feeding in the presence or absence of circulating exendin-4. Following the consumption of rodent or egg meals equivalent to 10% of lizard body mass, metabolic rates peaked at 4.0- to 4.9-fold of standard metabolic rates and remained elevated for 5-6 days. Specific dynamic action of these meals (43-60 kJ) was 13-18% of total meal energy. Feeding triggered significant increases in mucosal mass, enterocyte width and volume, and the upregulation of D-glucose uptake rates and aminopeptidase-N activity. Total intestinal uptake capacity for L-leucine, L-proline and D-glucose were significantly elevated within 1-3 days after feeding. Whereas the absence of circulating exendin-4 had no impact on postprandial metabolism or the postprandial response of intestinal structure and nutrient uptake, it significantly increased intestinal aminopeptidase-N activity. Within the continuum of physiological responses to feeding and fasting, Gila monsters occupy an intermediate position in experiencing moderate, though significant, regulation of intestinal performance with feeding. PMID- 17872998 TI - Differences in membrane acyl phospholipid composition between an endothermic mammal and an ectothermic reptile are not limited to any phospholipid class. AB - This study examined questions concerning differences in the acyl composition of membrane phospholipids that have been linked to the faster rates of metabolic processes in endotherms versus ectotherms. In liver, kidney, heart and brain of the ectothermic reptile, Trachydosaurus rugosus, and the endothermic mammal, Rattus norvegicus, previous findings of fewer unsaturates but a greater unsaturation index (UI) in membranes of the mammal versus those of the reptile were confirmed. Moreover, the study showed that the distribution of phospholipid head-group classes was similar in the same tissues of the reptile and mammal and that the differences in acyl composition were present in all phospholipid classes analysed, suggesting a role for the physical over the chemical properties of membranes in determining the faster rates of metabolic processes in endotherms. The most common phosphatidylcholine (PC) molecules present in all tissues (except brain) of the reptile were 16:0/18:1, 16:0/18:2, 18:0/18:2, 18:1/18:1 and 18:1/18:2, whereas arachidonic acid (20:4), containing PCs 16:0/20:4, 18:0/20:4, were the common molecules in the mammal. The most abundant phosphatidylethanolamines (PE) used in the tissue of the reptile were 18:0/18:2, 18:0/20:4, 18:1/18:1, 18:1/18:2 and 18:1/20:4, compared to 16:0/18:2, 16:0/20:4, 16:0/22:6, 18:0/20:4, 18:0/22:6 and 18:1/20:4 in the mammal. UI differences were primarily due to arachidonic acid found in both PC and PEs, whereas docosahexaenoic acid (22:6) was a lesser contributor mainly within PEs and essentially absent in the kidney. The phospholipid composition of brain was more similar in the reptile and mammal compared to those of other tissues. PMID- 17872999 TI - In vivo red blood cell sickling and mechanism of recovery in whiting, Merlangius merlangus. AB - Haemoglobin concentrations in vertebrate red blood cells are so high that in human sickle cell disease a single surface amino acid mutation can result in formation of large insoluble haemoglobin aggregates at low oxygen levels, causing peculiar cell deformations or 'sickling'. This may cause vascular occlusion and thereby severe pain, organ failure and death. Here, using light and transmission electron microscopy, we demonstrate extensive in vivo sickling of whiting red blood cells after capture stress without any apparent haemolysis and show its subsequent recovery. We show exceptionally high cooperative proton binding during the sickling process in vitro and identify the reduction of extracellular pH below resting values as the primary cause for in vivo sickling, although the response is modulated to a lesser extent also by oxygen tension. Using isotope tracer fluxes, we further show that beta-adrenergic hormones, which are released under capture stress, activate a powerful endogenous Na/H exchanger in these fish red blood cells, which is known to elevate intracellular pH. beta-adrenergic treatment further leads to a marked reduction of acid-induced in vitro sickling, which is impaired when Na/H exchange is inhibited by amiloride. We propose that this mechanism protects red blood cells of some fishes against the problem of haemoglobin aggregation and red blood cell sickling, except under most severe acidosis. This system offers a unique example of how, over evolutionary time, nature may have overcome what is still a deadly disease in humans. PMID- 17873000 TI - FoxK1 splice variants show developmental stage-specific plasticity of expression with temperature in the tiger pufferfish. AB - FoxK1 is a member of the highly conserved forkhead/winged helix (Fox) family of transcription factors and it is known to play a key role in mammalian muscle development and myogenic stem cell function. The tiger pufferfish (Takifugu rubripes) orthologue of mammalian FoxK1 (TFoxK1) has seven exons and is located in a region of conserved synteny between pufferfish and mouse. TFoxK1 is expressed as three alternative transcripts: TFoxK1-alpha, TFoxK1-gamma and TFoxK1 delta. TFoxK1-alpha is the orthologue of mouse FoxK1-alpha, coding for a putative protein of 558 residues that contains the forkhead and forkhead-associated domains typical of Fox proteins and shares 53% global identity with its mammalian homologue. TFoxK1-gamma and TFoxK1-delta arise from intron retention events and these transcripts translate into the same 344-amino acid protein with a truncated forkhead domain. Neither are orthologues of mouse FoxK1-beta. In adult fish, the TFoxK1 splice variants were differentially expressed between fast and slow myotomal muscle, as well as other tissues, and the FoxK1-alpha protein was expressed in myogenic progenitor cells of fast myotomal muscle. During embryonic development, TFoxK1 was transiently expressed in the developing somites, heart, brain and eye. The relative expression of TFoxK1-alpha and the other two alternative transcripts varied with the incubation temperature regime for equivalent embryonic stages and the differences were particularly marked at later developmental stages. The developmental expression pattern of TFoxK1 and its localisation to mononuclear myogenic progenitor cells in adult fast muscle indicate that it may play an essential role in myogenesis in T. rubripes. PMID- 17873001 TI - Interdependence of Ca2+ and proton movements in trout hepatocytes. AB - This study was undertaken to investigate possible interrelationships between Ca2+ homeostasis and pH regulation in trout hepatocytes. Exposure of cells to Ca2+ mobilizing agents ionomycin (0.5 micromol l(-1)) and thapsigargin (0.1 micromol l(-1)) induced an increase in intracellular pH (pHi) that was dependent on Ca2+ influx from the extracellular medium as well as Ca2+ release from intracellular pools. Surprisingly, this increase in pHi and intracellular Ca2+ concentration, [Ca2+]i, was not accompanied by any change in proton secretion. By contrast, removal of extracellular Ca2+ (Ca2+e) using EGTA (0.5 mmol l(-1)) briefly increased proton secretion rate with no apparent effect on pHi, while chelation of Ca2+i using BAPTA-AM (25 micromol l(-1)) resulted in a drop in pHi and a sustained increase in proton secretion rate. [Ca2+]i therefore affected intracellular proton distribution and/or proton production and also affected the distribution of protons across the cell membrane. Accordingly, changes in pHi were not always compensated for by proton secretion across the cell membrane. Alteration in pHe below and above normal values induced a slow, continuous increase in [Ca2+]i with a tendency to stabilize upon exposure to high pHe values. Rapid pHi increase induced by NH4Cl was accompanied by an elevation in [Ca2+]i from both extracellular and intracellular compartments. Ca2+e appeared to be involved in pHi regulation following NH4Cl-induced alkalinization whereas neither removal of Ca2+e nor chelation of Ca2+i affected pHi recovery following Na-propionate exposure. Similarly, [Ca2+]i increase induced by hypertonicity appeared to be a consequence of the changes in pHi as Na-free medium as well as cariporide diminished the hypertonicity-induced increase in [Ca2+]i. These results imply that a compensatory relationship between changes in pHi and proton secretion across cell plasma membrane is not always present. Consequently, calculating proton extrusion from buffering capacity and rate of pHi change cannot be taken as an absolute alternative for measuring proton secretion rate, at least in response to Ca2+ mobilizing agents. PMID- 17873002 TI - Heavy metal detoxification in crustacean epithelial lysosomes: role of anions in the compartmentalization process. AB - Crustacean hepatopancreatic lysosomes are organelles of heavy metal sequestration and detoxification. Previous studies have shown that zinc uptake by lysosomal membrane vesicles (LMV) occurred by a vanadate- and thapsigargin-sensitive ATPase that was stimulated by a transmembrane proton gradient established by a co localized V-ATPase associated with this organelle. In the present study, hepatopancreatic LMV from the American lobster Homarus americanus were prepared by standard centrifugation methods and 65Zn2+, 36Cl-, 35SO(4)2- and 14C-oxalate2- were used to characterize the interactions between the metal and anions during vesicular detoxification events. Vesicles loaded with SO4(2-) or PO(4)3- led to a threefold greater steady-state accumulation of Zn2+ than similar vesicles loaded with mannitol, Cl- or oxalate2-. The stimulation of 65Zn2+ uptake by intravesicular sulfate was SO(4)2- concentration dependent with a maximal enhancement at 500 micromol l(-1). Zinc uptake in the presence of ATP was proton gradient enhanced and electrogenic, exhibiting an apparent exchange stoichiometry of 1Zn+/3H+. 35SO4(2-) and 14C-oxalate2- uptakes were both enhanced in vesicles loaded with intravesicular Cl- compared to vesicles containing mannitol, suggesting the presence of anion countertransport. 35SO4(2-) influx was a sigmoidal function of external [SO(4)2-] with 25 mmol l(-1) internal [Cl-], or with several intravesicular pH values (e.g. 7.0, 8.0 and 9.0). In all instances Hill coefficients of approximately 2.0 were obtained, suggesting that 2 sulfate ions exchange with single Cl- or OH- ions. 36Cl- influx was a sigmoidal function of external [Cl-] with intravesicular pH of 7.0 and 9.0. A Hill coefficient of 2.0 was also obtained, suggesting the exchange of 2 Cl- for 1 OH-. 14C-oxalate influx was a hyperbolic function of external [oxalate2-] with 25 mmol l(-1) internal [Cl-], suggesting a 1:1 exchange of oxalate2- for Cl-. As a group, these experiments suggest the presence of an anion exchange mechanism exchanging monovalent for polyvalent anions. Polyvalent inorganic anions (SO4(2-) and PO4(3 )) are known to associate with metals inside vesicles and a detoxification model is presented that suggests how these anions may contribute to concretion formation through precipitation with metals at appropriate vesicular pH. PMID- 17873003 TI - Regulation of glycogen metabolism in gills and liver of the euryhaline tilapia (Oreochromis mossambicus) during acclimation to seawater. AB - Glucose, which plays a central role in providing energy for metabolism, is primarily stored as glycogen. The synthesis and degradation of glycogen are mainly initialized by glycogen synthase (GS) and glycogen phosphorylase (GP), respectively. The present study aimed to examine the glycogen metabolism in fish liver and gills during acute exposure to seawater. In tilapia (Oreochromis mossambicus) gill, GP, GS and glycogen were immunocytochemically colocalized in a specific group of glycogen-rich (GR) cells, which are adjacent to the gill's main ionocytes, mitochondrion-rich (MR) cells. Na+/K+-ATPase activity in the gills, protein expression and/or activity of GP and GS and the glycogen content of the gills and liver were examined in tilapia after their acute transfer from freshwater (FW) to 25 per thousand seawater (SW). Gill Na+/K+-ATPase activity rapidly increased immediately after SW transfer. Glycogen content in both the gills and liver were significantly depleted after SW transfer, but the depletion occurred earlier in gills than in the liver. Gill GP activity and protein expression were upregulated 1-3 h post-transfer and eventually recovered to the normal level as determined in the control group. At the same time, GS protein expression was downregulated. Similar changes in liver GP and GS protein expression were also observed but they occurred later at 6-12 h post-transfer. In conclusion, GR cells are initially stimulated to provide prompt energy for neighboring MR cells that trigger ion-secretion mechanisms. Several hours later, the liver begins to degrade its glycogen stores for the subsequent energy supply. PMID- 17873004 TI - Cooperative regulation of GSK-3 by muscarinic and PDGF receptors is associated with airway myocyte proliferation. AB - Muscarinic receptors and platelet-derived growth factor (PDGF) receptors synergistically induce proliferation of airway smooth muscle (ASM), but the pathways that regulate these effects are not yet completely identified. We hypothesized that glycogen synthase kinase-3 (GSK-3), a kinase that represses several promitogenic signaling pathways in its unphosphorylated form, is cooperatively inhibited by PDGF and muscarinic receptors in immortalized human ASM cell lines. PDGF or methacholine alone induced rapid GSK-3 phosphorylation. This phosphorylation was sustained only for PDGF; however, methacholine potentiated PDGF-induced sustained GSK-3 phosphorylation. Synergistic effects of methacholine also were observed on PDGF-induced retinoblastoma protein (Rb) phosphorylation and cell proliferation. Suppression of GSK-3 inhibitory function using SB 216763 also augmented PDGF-induced Rb phosphorylation and cell cycle progression; this synergy was similar in magnitude to that seen for methacholine with PDGF. GSK-3 phosphorylation induced by methacholine required PKC, since it was abolished by GF 109203X and Go 6976; however, inhibition of PKC had no effect on cell responses to PDGF. PKC inhibition also specifically abolished the synergistic effect of methacholine on PDGF-induced GSK-3 phosphorylation and cell proliferation. Collectively, these results show that GSK-3 plays a key repressive role in ASM cell proliferation. Moreover, muscarinic receptors mediate PKC dependent GSK-3 inhibition, and this appears to be a primary mechanism underpinning augmentation of PDGF-induced cell growth. PMID- 17873005 TI - Dexamethasone prevents transport inhibition by hypoxia in rat lung and alveolar epithelial cells by stimulating activity and expression of Na+-K+-ATPase and epithelial Na+ channels. AB - Hypoxia inhibits Na and lung fluid reabsorption, which contributes to the formation of pulmonary edema. We tested whether dexamethasone prevents hypoxia induced inhibition of reabsorption by stimulation of alveolar Na transport. Fluid reabsorption, transport activity, and expression of Na transporters were measured in hypoxia-exposed rats and in primary alveolar type II (ATII) cells. Rats were treated with dexamethasone (DEX; 2 mg/kg) on 3 consecutive days and exposed to 10% O(2) on the 2nd and 3rd day of treatment to measure hypoxia effects on reabsorption of fluid instilled into lungs. ATII cells were treated with DEX (1 muM) for 3 days before exposure to hypoxia (1.5% O(2)). In normoxic rats, DEX induced a twofold increase in alveolar fluid clearance. Hypoxia decreased reabsorption (-30%) by decreasing its amiloride-sensitive component; pretreatment with DEX prevented the hypoxia-induced inhibition. DEX increased short-circuit currents (ISC) of ATII monolayers in normoxia and blunted hypoxic transport inhibition by increasing the capacity of Na(+)-K(+)-ATPase and epithelial Na(+) channels (ENaC) and amiloride-sensitive ISC. DEX slightly increased the mRNA of alpha- and gamma-ENaC in whole rat lung. In ATII cells from DEX-treated rats, mRNA of alpha(1)-Na(+)-K(+)-ATPase and alpha-ENaC increased in normoxia and hypoxia, and gamma-ENaC was increased in normoxia only. DEX stimulated the mRNA expression of alpha(1)-Na(+)-K(+)-ATPase and alpha-, beta-, and gamma-ENaC of A549 cells in normoxia and hypoxia (1.5% O(2)) when DEX treatment was begun before or during hypoxic exposure. These results indicate that DEX prevents inhibition of alveolar reabsorption by hypoxia and stimulates the expression of Na transporters even when it is applied in hypoxia. PMID- 17873006 TI - Proinflammatory responses of human airway cells to ricin involve stress-activated protein kinases and NF-kappaB. AB - Ricin is a potential bioweapon because of its toxicity, availability, and ease of production. When delivered to the lungs, ricin causes severe pulmonary damage with symptoms that are similar to those observed in acute lung injury and adult respiratory distress syndrome. The airway epithelium plays an important role in the pathogenesis of many lung diseases, but its role in ricin intoxication has not been elucidated. Exposure of cultured primary human airway epithelial cells to ricin resulted in the activation of SAPKs and NF-kappaB and in the increased expression of multiple proinflammatory molecules. Among the genes upregulated by ricin and identified by microarray analysis were those associated with transcription, nucleosome assembly, inflammation, and response to stress. Sequence analysis of the promoters of these genes identified NF-kappaB as one of the transcription factors whose binding sites were overrepresented. Although airway cells secrete TNF-alpha in response to ricin, blocking TNF-alpha did not prevent ricin-induced activation of NF-kappaB. Decreased levels of IkappaB-alpha in airway cells exposed to ricin suggest that translational suppression may be responsible for the activation of NF-kappaB. Inhibition of p38 MAPK by a chemical inhibitor or NF-kappaB by short interfering RNA resulted in a marked reduction in the expression of proinflammatory genes, demonstrating the importance of these two pathways in ricin intoxication. Therefore, the p38 MAPK and NF-kappaB pathways are potential therapeutic targets for reducing the inflammatory consequences of ricin poisoning. PMID- 17873007 TI - Involvement of chloride channels in TGF-beta1-induced apoptosis of human bronchial epithelial cells. AB - Widespread damage of airway epithelium and defective epithelial repair are hallmarks of chronic asthma. Growth factors and cytokines spatially and temporally regulate epithelial shedding and repair. Within this context, a key function is exerted by transforming growth factor (TGF)-beta. Recent growing evidence suggests that chloride (Cl(-)) channels are critical to cell apoptosis. We examined the effects of TGF-beta1 on Cl(-) channel expression and activity and its relationship with apoptosis in human bronchial epithelial cells (HBECs). The small interfering RNA (siRNA) approach was used to investigate the potential role of CLC-3, a member of the volume-regulated Cl(-) channel family, in apoptosis of HBECs. TGF-beta1 significantly induced HBEC apoptosis, which paralleled to a significant decrease in the endogenous expression of CLC-3 protein and mRNA transcripts. Outward rectifying and voltage-dependent CLC-3-like Cl(-) currents in HBECs were diminished by TGF-beta1. siRNA for CLC-3 abolished Cl(-) current and enhanced TGF-beta1-induced cell apoptosis. Overexpression of CLC-3 in HBECs inhibited TGF-beta1-induced cell apoptosis. Bcl-2 was also downregulated after TGF-beta stimulation. TGF-beta1-induced cell apoptosis was suppressed in Bcl-2 transfected HBECs. Our data demonstrate that CLC-3-like voltage-gated chloride channels play a critical role in TGF-beta-induced apoptosis of human airway epithelial cells. PMID- 17873008 TI - CRYAB and HSPB2 deficiency alters cardiac metabolism and paradoxically confers protection against myocardial ischemia in aging mice. AB - The abundantly expressed small molecular weight proteins, CRYAB and HSPB2, have been implicated in cardioprotection ex vivo. However, the biological roles of CRYAB/HSPB2 coexpression for either ischemic preconditioning and/or protection in situ remain poorly defined. Wild-type (WT) and age-matched ( approximately 5-9 mo) CRYAB/HSPB2 double knockout (DKO) mice were subjected either to 30 min of coronary occlusion and 24 h of reperfusion in situ or preconditioned with a 4-min coronary occlusion/4-min reperfusion x 6, before similar ischemic challenge (ischemic preconditioning). Additionally, WT and DKO mice were subjected to 30 min of global ischemia in isolated hearts ex vivo. All experimental groups were assessed for area at risk and infarct size. Mitochondrial respiration was analyzed in isolated permeabilized cardiac skinned fibers. As a result, DKO mice modestly altered heat shock protein expression. Surprisingly, infarct size in situ was reduced by 35% in hearts of DKO compared with WT mice (38.8 +/- 17.9 vs. 59.8 +/- 10.6% area at risk, P < 0.05). In DKO mice, ischemic preconditioning was additive to its infarct-sparing phenotype. Similarly, infarct size after ischemia and reperfusion ex vivo was decreased and the production of superoxide and creatine kinase release was decreased in DKO compared with WT mice (P < 0.05). In permeabilized fibers, ADP-stimulated respiration rates were modestly reduced and calcium-dependent ATP synthesis was abrogated in DKO compared with WT mice. In conclusion, contrary to expectation, our findings demonstrate that CRYAB and HSPB2 deficiency induces profound adaptations that are related to 1) a reduction in calcium-dependent metabolism/respiration, including ATP production, and 2) decreased superoxide production during reperfusion. We discuss the implications of these disparate results in the context of phenotypic responses reported for CRYAB/HSPB2-deficient mice to different ischemic challenges. PMID- 17873009 TI - Contribution of polyol pathway to arteriolar dysfunction in hyperglycemia. Role of oxidative stress, reduced NO, and enhanced PGH(2)/TXA(2) mediation. AB - Hyperglycemia increases glucose metabolism via the polyol pathway, which results in elevations of intracellular sorbitol concentration. Thus we hypothesized that elevated level of sorbitol contributes to the development of hyperglycemia induced dysfunction of microvessels. In isolated, pressurized (80 mmHg) rat gracilis muscle arterioles (approximately 150 microm), high glucose treatment (25 mM) induced reduction in flow-dependent dilation (from maximum of 39 +/- 2% to 15 +/- 1%), which was significantly mitigated by an aldose reductase inhibitor, zopolrestat (maximum 27 +/- 2%). Increasing doses of sorbitol (10(-10)-10(-4) M) elicited dose-dependent constrictions (maximum 22 +/- 3%), which were abolished by endothelium removal, a prostaglandin H(2)/thromboxane A(2) (PGH(2)/TXA(2)) receptor (TP) antagonist SQ-29548, or superoxide dismutase (SOD) plus catalase (CAT). Incubation of arterioles with sorbitol (10(-7) M) reduced flow-dependent dilations (from maximum of 39 +/- 2% to 20 +/- 1.5%), which was not further affected by inhibition of nitric oxide synthase by N(omega)-nitro-l-arginine methyl ester but was prevented by SOD plus CAT and mitigated by SQ-29548. Nitric oxide donor sodium nitroprusside-induced (10(-9)-10(-6) M) dilations were also decreased in a SQ-29548 and SOD plus CAT-reversible manner, whereas adenosine dilations were not affected by sorbitol exposure. Sorbitol significantly increased arterial superoxide production detected by lucigenin-enhanced chemiluminescence, which was inhibited by SOD plus CAT. Sorbitol treatment also increased arterial formation of 3-nitrotyrosine. We suggest that hyperglycemia by elevating intracellular sorbitol induces oxidative stress, which interferes with nitric oxide bioavailability and promotes PGH(2)/TXA(2) release, both of which affect regulation of vasomotor responses of arterioles. Thus increased activity of the polyol pathway may contribute to the development of microvascular dysfunction in diabetes mellitus. PMID- 17873010 TI - Hydrogen sulfide preconditioning by garlic when it starts to smell. PMID- 17873011 TI - Xin and the art of intercalated disk maintenance. PMID- 17873012 TI - Vascular smooth muscle G(q) signaling is involved in high blood pressure in both induced renal and genetic vascular smooth muscle-derived models of hypertension. AB - More than 30% of the US population has high blood pressure (BP), and less than a third of people treated for hypertension have it controlled. In addition, the etiology of most high BP is not known. Having a better understanding of the mechanisms underlying hypertension could potentially increase the effectiveness of treatment. Because G(q) signaling mediates vasoconstriction and vascular function can cause BP abnormalities, we were interested in determining the role of vascular smooth muscle (VSM) G(q) signaling in two divergent models of hypertension: a renovascular model of hypertension through renal artery stenosis and a genetic model of hypertension using mice with VSM-derived high BP. Inhibition of VSM G(q) signaling attenuated BP increases induced by renal artery stenosis to a similar extent as losartan, an ANG II receptor blocker and current antihypertensive therapy. Inhibition of G(q) signaling also attenuated high BP in our genetic VSM-derived hypertensive model. In contrast, BP remained elevated 25% following treatment with losartan, and prazosin, an alpha(1)-adrenergic receptor antagonist, only decreased BP by 35%. Inhibition of G(q) signaling attenuated VSM reactivity to ANG II and resulted in a 2.4-fold rightward shift in EC(50). We also determined that inhibition of G(q) signaling was able to reverse VSM hypertrophy in the genetic VSM-derived hypertensive model. These results suggest that G(q) signaling is an important signaling pathway in two divergent models of hypertension and, perhaps, optimization of antihypertensive therapy could occur with the identification of particular G(q)-coupled receptors involved. PMID- 17873013 TI - Cerebrovascular ETB, 5-HT1B, and AT1 receptor upregulation correlates with reduction in regional CBF after subarachnoid hemorrhage. AB - We hypothesize that cerebral ischemia leads to enhanced expression of endothelin (ET), 5-hydroxytryptamine (5-HT), and angiotensin II (ANG II) receptors in the vascular smooth muscle cells. Our aim is to correlate the upregulation of cerebrovascular receptors and the underlying molecular mechanisms with the reduction in regional and global cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH). SAH was induced by injecting 250 microl blood into the prechiasmatic cistern in rats. The cerebral arteries were removed 0, 1, 3, 6, 12, 24, and 48 h after the SAH for functional and molecular studies. The contractile responses to ET-1, 5-carboxamidotryptamine (5-CT), and ANG II were investigated with myograph. The receptor mRNA and protein levels were analyzed by quantitative real-time PCR and immunohistochemistry, respectively. In addition, regional and global CBFs were measured by an autoradiographic method. As a result, SAH resulted in enhanced contractions to ET-1 and 5-CT. ANG II [via ANG II type 1 (AT(1)) receptors] induced increased contractile responses [in the presence of the ANG II type 2 (AT(2)) receptor antagonist PD-123319]. In parallel the ET(B), 5-HT(1B), and AT(1) receptor, mRNA and protein levels were elevated by time. The regional and global CBF showed a successive reduction with time after SAH. In conclusion, the results demonstrate for the first time that SAH induces the upregulation of ET(B), 5-HT(1B), and AT(1) receptors in a time-dependent manner both at functional, mRNA, and protein levels. These changes occur in parallel with a successive decrease in CBF. Thus there is a temporal correlation between the changes in receptor expression and CBF reduction, suggesting a linkage. PMID- 17873014 TI - Delayed expression of cytokines after reperfused myocardial infarction: possible trigger for cardiac dysfunction and ventricular remodeling. AB - Previous studies have shown that 1 wk after permanent coronary artery ligation in rats, some cellular mechanisms involving TNF-alpha occur and contribute to the development of cardiac dysfunction and subsequent heart failure. The aim of the present study was to determine whether similar phenomena also occur after ischemia-reperfusion and whether cytokines other than TNF-alpha can also be involved. Anesthetized male Wistar rats were subjected to 1 h coronary occlusion followed by reperfusion. Cardiac geometry and function were assessed by echocardiography at days 5, 7, 8, and 10 postligation. Before death, heart function was assessed in vivo under basal conditions, as well as after volume overload. Finally, hearts were frozen for histoenzymologic assessment of infarct size and remodeling. The profile of cardiac cytokines was determined by ELISA and ChemiArray on heart tissue extracts. As expected, ischemia-reperfusion induced a progressive remodeling of the heart, characterized by left ventricular free-wall thinning and cavity dilation. Heart function was also decreased in ischemic rats during the first week after surgery. Interestingly, a transient and marked increase in TNF-alpha, IL-1beta, IL-6, cytokine-induced neutrophil chemoattractant (CINC) 2, CINC3, and macrophage inflammatory protein-3alpha was also observed in the myocardium of myocardial ischemia (MI) animals at day 8, whereas the expression of anti-inflammatory interleukins IL-4 and IL-10 remained unchanged. These results suggest that overexpression of proinflammatory cytokines occurring during the first week after ischemia-reperfusion may play a role in the adaptative process in the myocardium and contribute to early dysfunction and remodeling. PMID- 17873015 TI - The balance between inactivation and activation of the Na+-K+ pump underlies the triphasic accumulation of extracellular K+ during myocardial ischemia. AB - Ischemia-induced hyperkalemia (accumulation of extracellular K(+)) predisposes the heart to the development of lethal reentrant ventricular arrhythmias. This phenomenon exhibits a triphasic time course and is thought to be mediated by a combination of three mechanisms: 1) increased cellular K(+) efflux, 2) decreased cellular K(+) influx, and 3) shrinkage of the extracellular space. These ischemia induced electrophysiological changes are driven by an impaired cellular metabolism. However, the relative contributions of these mechanisms, as well as the origin of the triphasic profile, have proven to be difficult to determine experimentally. In this study, the changes in metabolite concentrations that arise during 15 min of zero-flow global ischemia were incorporated into a dynamic model of cellular electrophysiology, which was extended to include a metabolically sensitive description of the Na(+)-K(+) pump and ATP-sensitive K(+) channel, in addition to cell volume regulation. The coupling of altered K(+) fluxes and cell volume regulation enables an integrative simulation of ischemic hyperkalemia. These simulations were able to quantitatively reproduce experimental measurements of the accumulation of extracellular K(+) during 15 min of simulated ischemia, both with respect to the degree of K(+) loss as well as the triphasic time course. Analysis of the model indicates that the inhibition of the Na(+)-K(+) pump is the dominant factor underlying this hyperkalemic behavior, accounting for approximately 85% of the observed extracellular K(+) accumulation. It was found that the balance between activation and inhibition of the Na(+)-K(+) pump, affected by the changing metabolite and ion concentrations (in particular, [ADP]), give rise to the triphasic profile associated with ischemic hyperkalemia. PMID- 17873016 TI - Adenylyl cyclase activity and function are decreased in rat cardiac fibroblasts after myocardial infarction. AB - Myocardial infarction (MI) results in left ventricular remodeling (e.g., ventricular hypertrophy, dilatation, and fibrosis). Fibrosis contributes to increased myocardial stiffening, impaired ventricular filling and function, and reduced cardiac output. Adenylyl cyclase (AC) expression and activity are reduced in animal models of heart failure. Stimulation of AC can inhibit extracellular matrix production in isolated cardiac fibroblasts; however, a role for reduced AC expression and activity in fibrosis associated with cardiac remodeling after chronic MI has never been determined. We tested the hypothesis that AC expression and activity are reduced in cardiac fibroblasts after chronic (18 wk) MI. Rats underwent coronary artery ligation or sham surgery (control), and echocardiography was used to assess left ventricular remodeling 1, 3, 5, 7, 10, 12, and 18 wk after surgery. Cardiac fibroblasts were isolated from the noninfarcted myocardium and compared for differences in AC activity and collagen synthesis. End-diastolic dimension was increased [control: 0.76 +/- 0.02 cm and MI: 1.0 +/- 0.02 cm (means +/- SE), P < 0.001] and fractional shortening was decreased (control: 44 +/- 2% and MI: 17 +/- 2%, P < 0.001) in MI compared with control rats. Basal and forskolin-stimulated cAMP production were decreased by 90% and 93%, respectively, and AC5/6 expression was decreased 39% in fibroblasts isolated from MI rats compared with sham controls. Serum-stimulated collagen production was increased twofold and forskolin-mediated inhibition of collagen synthesis was reduced in fibroblasts from MI rats compared with controls. Our data demonstrate that AC expression and activity are reduced and collagen production is increased in cardiac fibroblasts of rats after MI. PMID- 17873017 TI - Differential effects of left ventricular pacing sites in an acute canine model of contraction dyssynchrony. AB - The goal of the present study was to assess the effects of left ventricular (LV) pacing sites (apex vs. free wall) on radial synchrony and global LV performance in a canine model of contraction dyssynchrony. Ultrasound tissue Doppler imaging and hemodynamic (LV pressure-volume) data were collected in seven anesthetized, opened-chest dogs. Right atrial (RA) pacing served as the control, and contraction dyssynchrony was created by simultaneous RA and right ventricular (RV) pacing to induce a left bundle-branch block-like contraction pattern. Cardiac resynchronization therapy (CRT) was implemented by adding simultaneous LV pacing to the RV pacing mode at either the LV apex (CRTa) or free wall (CRTf). A new index of synchrony was developed via pair-wise cross-correlation analysis of tissue Doppler radial strain from six midmyocardial cross-sectional regions, with a value of 15 indicating perfect synchrony. Compared with RA pacing, RV pacing significantly decreased radial synchrony (11.1 +/- 0.8 vs. 4.8 +/- 1.2, P < 0.01) and global LV performance (cardiac output: 2.0 +/- 0.3 vs. 1.4 +/- 0.1 l/min and stroke work: 137 +/- 22 vs. 60 +/- 14 mJ, P < 0.05). Although both CRTa and CRTf significantly improved radial synchrony, only CRTa markedly improved global function (cardiac output: 2.1 +/- 0.2 l/min and stroke work: 113 +/- 13 mJ, P < 0.01 vs. RV pacing). Furthermore, CRTa decreased LV end-systolic volume compared with RV pacing without any change in LV end-systolic pressure, indicating an augmented global LV contractile state. Thus, LV apical pacing appears to be a superior pacing site in the context of CRT. The dissociation between changes in synchrony and global LV performance with CRTf suggests that regional analysis from a single plane may not be sufficient to adequately characterize contraction synchrony. PMID- 17873018 TI - Surrounding tissues affect the passive mechanics of the vessel wall: theory and experiment. AB - The stress and strain in the vessel wall are important determinants of vascular physiology and pathophysiology. Vessels are constrained radially by the surrounding tissue. The hypothesis in this work is that the surrounding tissue takes up a considerable portion of the intravascular pressure and significantly reduces the wall strain and stress. Ten swine of either sex were used to test this hypothesis. An impedance catheter was inserted into the carotid or femoral artery, and after mechanical preconditioning pressure-cross-sectional area relations were obtained with the surrounding tissue intact and dissected away (untethered), respectively. The radial constraint of the surrounding tissue was quantified as an effective perivascular pressure on the outer surface of the vessel, which was estimated as 50% or more of the intravascular pressure. For carotid arteries at pressure of 100 mmHg, the circumferential wall stretch ratio in the intact state was approximately 20% lower than in the untethered state and the average circumferential stress was reduced by approximately 70%. For femoral arteries, the reductions were approximately 15% and 70%, respectively. These experimental data support the proposed hypothesis and suggest that in vitro and in vivo measurements of the mechanical properties of vessels must be interpreted with consideration of the constraint of the surrounding tissue. PMID- 17873019 TI - Chronic high blood flow potentiates shear stress-induced release of NO in arteries of aged rats. AB - Aging impairs shear-stress-dependent dilation of arteries via increased superoxide production, decreased SOD activity, and decreased activation of endothelial nitric oxide (NO) synthase (eNOS). In the present study, we investigated whether chronic increases in shear stress, elicited by increases in blood flow, would improve vascular endothelial function of aged rats. To this end, second-order mesenteric arteries of young (6 mo) and aged (24 mo) male Fischer-344 rats were selectively ligated for 3 wk to elevate blood flow in a first-order artery [high blood flow (HF)]. An in vitro study was then conducted on first-order arteries with HF and normal blood flow (NF) to assess shear stress (1, 10, and 20 dyn/cm(2))-induced release of NO into the perfusate. In HF arteries of both age groups, shear stress-induced NO production increased significantly. In 24-mo-old rats, the reduced shear stress-induced NO production in NF arteries was normalized by HF to a level similar to that in NF arteries of 6-mo-old rats. The increased NO production in HF arteries of 24-mo-old rats was associated with increased shear stress-induced dilation, expression of eNOS protein, and shear stress-induced eNOS phosphorylation. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, reduced shear stress-induced eNOS phosphorylation and vasodilation. Superoxide production decreased significantly in HF compared with NF arteries in 24-mo-old rats. The decreased superoxide production was associated with significant increases in CuZn-SOD and extracellular SOD protein expressions and total SOD activity. These results suggest that stimulation with chronic HF restores shear-stress-induced activation of eNOS and antioxidant ability in aged arteries. PMID- 17873020 TI - Chaperone-dependent E3 ligase CHIP ubiquitinates and mediates proteasomal degradation of soluble guanylyl cyclase. AB - The nitric oxide receptor soluble guanylyl cyclase (sGC) exists in multimeric protein complexes, including heat shock protein (HSP) 90 and endothelial nitric oxide synthase. Inhibition of HSP90 by geldanamycin causes proteasomal degradation of sGC protein. In this study, we have investigated whether COOH terminus of heat shock protein 70-interacting protein (CHIP), a co-chaperone molecule that is involved in protein folding but is also a chaperone-dependent ubiquitin E3 ligase, could play a role in the process of degradation of sGC. Transient overexpression of CHIP in COS-7 cells degraded heterologous sGC in a concentration-related manner; this downregulation of sGC was abrogated by the proteasome inhibitor MG-132. Transfection of tetratricopeptide repeats and U-box domain CHIP mutants attenuated sGC degradation, suggesting that both domains are indispensable for CHIP function. Results from immunoprecipitation and indirect immunofluorescent microscopy experiments demonstrated that CHIP is associated with sGC, HSP90, and HSP70 in COS-7 cells. Furthermore, CHIP increased the association of HSP70 with sGC. In in vitro ubiquitination assays using purified proteins and ubiquitin enzymes, E3 ligase CHIP directly ubiquitinated sGC; this ubiquitination was potentiated by geldanamycin in COS-7 cells, followed by proteasomal degradation. In rat aortic smooth muscle cells, endogenous sGC was also degraded by adenovirus-infected wild-type CHIP but not by the chaperone interaction-deficient K30A CHIP, whereas CHIP, but not K30A, attenuated sGC expression in, and nitric oxide donor-induced relaxation of, rat aortic rings, suggesting that CHIP plays a regulatory role under physiological conditions. This study reveals a new mechanism for the regulation of sGC, an important mediator of cellular and vascular function. PMID- 17873021 TI - Characterization and mechanism of P2X receptor-mediated increase in cardiac myocyte contractility. AB - Cardiac P2X purinergic receptors can mediate an increase in myocyte contractility and a potentially important role in the heart. The P2X(4) receptor (P2X(4)R) is an important subunit of native cardiac P2X receptors. With transgenic mice with cardiac-specific overexpression of P2X(4)R (Tg) used as a model, the objectives here were to characterize the P2X receptor-mediated cellular contractile and Ca(2+) transient effects and to determine the mechanism underlying the receptor induced increase in myocyte contractility. In response to the agonist 2 methylthioATP (2-meSATP), Tg myocytes showed an increased intracellular Ca(2+) transient, as defined by fura 2 fluorescence ratio, and an enhanced contraction shortening that were unaccompanied by cAMP accumulation or L-type Ca(2+) channel activation. The increased Ca(2+) transient was not associated with any alteration in action potential duration, resting membrane potential, or diastolic fluorescence ratio or rates of rise and decline of the Ca(2+) transient. Simultaneous Ca(2+) transient and contraction measurements did not show any agonist-mediated change in myofilament Ca(2+) sensitivity. However, activation of the overexpressed P2X(4) receptor caused an enhanced SR Ca(2+) loading, as evidenced by a 2-meSATP-evoked increase in the caffeine-induced inward current and Ca(2+) transient. Similar data were obtained in wild-type mouse ventricular myocytes. Thus an increased SR Ca(2+) content, occurring in the absence of cAMP accumulation or L-type Ca(2+) channel activation, is the principal mechanism by which cardiac P2X receptor mediates a stimulatory effect on cardiac myocyte contractility. PMID- 17873022 TI - Cardiovascular effects of intravenous ghrelin infusion in healthy young men. AB - Ghrelin infusion improves cardiac function in patients suffering from cardiac failure, and bolus administration of ghrelin increases cardiac output in healthy subjects. The cardiovascular effects of more continuous intravenous ghrelin exposure remain to be studied. We therefore studied the cardiovascular effects of a constant infusion of human ghrelin at a rate of 5 pmol/kg per minute for 180 min. Fifteen healthy, young (aged 23.2 +/- 0.5 yr), normal-weight (23.0 +/- 0.4 kg/m(2)) men volunteered in a randomized double-blind, placebo-controlled crossover study. With the subjects remaining fasting, peak myocardial systolic velocity S', tissue tracking TT, left ventricular ejection fraction EF, and endothelium-dependent flow-mediated vasodilatation were measured. Ghrelin infusion increased S' 9% (P = 0.002) and TT 10% (P < 0.001), whereas EF, resting blood flow velocity, and endothelium-dependent flow-mediated vasodilatation did not change (P = 0.13). This was associated with a peak in serum growth hormone after 60 min of infusion (37.77 +/- 5.27 ng/ml, P < 0.001), a doubling of free fatty acid levels (P = 0.001), and a 1.6-fold increase in cortisol levels (P < 0.05), whereas glucose and catecholamine levels were constant. In conclusion, supraphysiological levels of ghrelin stimulate left ventricular function in terms of S' and TT in healthy young normal-weight men without changing resting blood flow velocity and endothelium-dependent flow-mediated vasodilatation. The effects did not translate into detectable increments in EF. PMID- 17873023 TI - Growth-related oncogene-alpha induces endothelial dysfunction through oxidative stress and downregulation of eNOS in porcine coronary arteries. AB - Growth-related oncogene-alpha (GRO-alpha) is a member of the CXC chemokine family, which is involved in the inflammatory process including atherosclerosis. We hypothesized that GRO-alpha may affect endothelial functions in both porcine coronary arteries and human coronary artery endothelial cells (HCAECs). Vasomotor function was analyzed in response to thromboxane A2 analog U-46619 for contraction, bradykinin for endothelium-dependent vasorelaxation, and sodium nitroprusside (SNP) for endothelium-independent vasorelaxation. In response to 10(-6) M bradykinin, GRO-alpha (50 and 100 ng/ml) significantly reduced endothelium-dependent vasorelaxation by 34.73 and 48.8%, respectively, compared with controls (P < 0.05). There were no changes in response to U-46619 or SNP between treated and control groups. With the lucigenin-enhanced chemiluminescence assay, superoxide anion production in GRO-alpha-treated vessels (50 and 100 ng/ml) was significantly increased by 50 and 86%, respectively, compared with controls (P < 0.05). With real-time PCR analysis, endothelial nitric oxide synthase (eNOS) mRNA levels in porcine coronary arteries and HCAECs after GRO alpha treatment were significantly decreased compared with controls (P < 0.05). The eNOS protein levels by both immunohistochemistry and Western blot analyses were also decreased in GRO-alpha-treated vessels. Antioxidant seleno-l-methionine and anti-GRO-alpha antibody effectively blocked these effects of GRO-alpha on both porcine coronary arteries and HCAECs. In addition, GRO-alpha immunoreactivity was substantially increased in the atherosclerotic regions compared with nonatherosclerotic regions in human coronary arteries. Thus GRO alpha impairs endothelium-dependent vasorelaxation in porcine coronary arteries through a mechanism of overproduction of superoxide anion and downregulation of eNOS. GRO-alpha may contribute to human coronary artery disease. PMID- 17873024 TI - Development of progressive aortic vasculopathy in a rat model of aging. AB - Recent studies have established that age is the major risk factor for vascular disease. Numerous aberrant changes occur in vascular structure and function during aging, and animal models are the primary means to determine the underlying mechanisms of age-mediated vascular pathology. The Fischer 344/Brown Norway F1 hybrid (F344xBN) rat thoracic aorta has been shown to display age-related pathology similar to what occurs in humans. This study utilized the F344xBN rat aorta and both morphometric and global gene expression analyses to identify appropriate time points to study vascular aging and to identify molecules associated with the development and progression of vascular pathology. In contrast to some previous studies that indicated age-related abrupt changes, a progressive increase in intimal and medial thickness, as well as smooth muscle cell-containing intimal protrusions, was observed in thoracic aorta. This structural vascular pathology was associated with a progressive, but nonlinear, increase in global differential gene expression. Gene products with altered mRNA and protein expression included inflammation-related molecules: specifically, the adhesion molecules ICAM-1 and VCAM-1 and the bone morphogenic proteins osteopontin and bone sialoprotein-1. Intimal-associated macrophages were found to increase significantly in number with age. Both systemic and tissue markers of oxidant stress, serum 8-isoprostane and 3-nitrotyrosine, respectively, were also found to increase during aging. The results demonstrate that major structural abnormalities and altered gene expression develop after 6 mo and that the progressive pathological development is associated with increased inflammation and oxidant stress. PMID- 17873025 TI - Doxorubicin-induced cardiotoxicity: direct correlation of cardiac fibroblast and H9c2 cell survival and aconitase activity with heat shock protein 27. AB - The use of doxorubicin (Dox) and its derivatives as chemotherapeutic drugs to treat patients with cancer causes dilated cardiomyopathy and congestive heart failure due to Dox-induced cardiotoxicity. In this work, using heat shock factor 1 wild-type (HSF-1(+/+)) and HSF-1 knockout (HSF-1(-/-)) mouse fibroblasts and embryonic rat heart-derived cardiac H9c2 cells, we show that the magnitude of protection from Dox-induced toxicity directly correlates with the level of the heat shock protein 27 (HSP27). Western blot analysis of normal and heat-shocked cells showed the maximum expression of HSP27 in heat-shocked cardiac H9c2 cells and no HSP27 in HSF-1(-/-) cells (normal or heat-shocked). Correspondingly, the cell viability, measured [with (3,4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay] after treatment with various concentrations of Dox, was the highest in heat-shocked H9c2 cells and the lowest in HSF-1(-/-) cells. Depleting HSP27 in cardiac H9c2 cells by small interfering (si)RNA also reduced the viability against Dox, confirming that HSP27 does protect cardiac cells against the Dox-induced toxicity. The cells that have lower HSP27 levels such as HSF-1(-/-), were found to be more susceptible for aconitase inactivation. Based on these results we propose a novel mechanism that HSP27 plays an important role in protecting aconitase from Dox-generated O(2)*(-), by increasing SOD activity. Such a protection of aconitase by HSP27 eliminates the catalytic recycling of aconitase released Fe(II) and its deleterious effects in cardiac cells. PMID- 17873026 TI - Hemodynamics and muscle sympathetic nerve activity after 8 h of sustained hypoxia in healthy humans. AB - Hemodynamics, muscle sympathetic nerve activity (MSNA), and forearm blood flow were evaluated in 12 normal subjects before, during (1 and 7 h), and after ventilatory acclimatization to hypoxia achieved with 8 h of continuous poikilocapnic hypoxia. All results are means +/- SD. Subjects experienced mean oxygen saturation of 84.3 +/- 2.3% during exposure. The exposure resulted in hypoxic acclimatization as suggested by end-tidal CO(2) [44.7 +/- 2.7 (pre) vs. 39.5 +/- 2.2 mmHg (post), P < 0.001] and by ventilatory response to hypoxia [1.2 +/- 0.8 (pre) vs. 2.3 +/- 1.3 l x min(-1).1% fall in saturation(-1) (post), P < 0.05]. Subjects exhibited a significant increase in heart rate across the exposure that remained elevated even upon return to room air breathing compared with preexposure (67.3 +/- 15.9 vs. 59.8 +/- 12.1 beats/min, P < 0.008). Although arterial pressure exhibited a trend toward an increase across the exposure, this did not reach significance. MSNA initially increased from room air to poikilocapnic hypoxia (26.2 +/- 10.3 to 32.0 +/- 10.3 bursts/100 beats, not significant at 1 h of exposure); however, MSNA then decreased below the normoxic baseline despite continued poikilocapnic hypoxia (20.9 +/- 8.0 bursts/100 beats, 7 h Hx vs. 1 h Hx; P < 0.008 at 7 h). MSNA decreased further after subjects returned to room air (16.6 +/- 6.0 bursts/100 beats; P < 0.008 compared with baseline). Forearm conductance increased after exposure from 2.9 +/- 1.5 to 4.3 +/- 1.6 conductance units (P < 0.01). These findings indicate alterations of cardiovascular and respiratory control following 8 h of sustained hypoxia producing not only acclimatization but sympathoinhibition. PMID- 17873027 TI - Hypertension-induced remodeling of cardiac excitation-contraction coupling in ventricular myocytes occurs prior to hypertrophy development. AB - Hypertension is a major risk factor for developing cardiac hypertrophy and heart failure. Previous studies show that hypertrophied and failing hearts display alterations in excitation-contraction (E-C) coupling. However, it is unclear whether remodeling of the E-C coupling system occurs before or after heart disease development. We hypothesized that hypertension might cause changes in the E-C coupling system that, in turn, induce hypertrophy. Here we tested this hypothesis by utilizing the progressive development of hypertensive heart disease in the spontaneously hypertensive rat (SHR) to identify a window period when SHR had just developed hypertension but had not yet developed hypertrophy. We found the following major changes in cardiac E-C coupling during this window period. 1) Using echocardiography and hemodynamics measurements, we found a decrease of left ventricular ejection fraction and cardiac output after the onset of hypertension. 2) Studies in isolated ventricular myocytes showed that myocardial contraction was also enhanced at the same time. 3) The action potential became prolonged. 4) The E-C coupling gain was increased. 5) The systolic Ca(2+) transient was augmented. These data show that profound changes in E-C coupling already occur at the onset of hypertension and precede hypertrophy development. Prolonged action potential and increased E-C coupling gain synergistically increase the Ca(2+) transient. Functionally, augmented Ca(2+) transient causes enhancement of myocardial contraction that can partially compensate for the greater workload to maintain cardiac output. The increased Ca(2+) signaling cascade as a molecular mechanism linking hypertension to cardiac hypertrophy development is also discussed. PMID- 17873028 TI - Aging is associated with myocardial insulin resistance and mitochondrial dysfunction. AB - Aging is associated with insulin resistance, often attributable to obesity and inactivity. Recent evidence suggests that skeletal muscle insulin resistance in aging is associated with mitochondrial alterations. Whether this is true of the senescent myocardium is unknown. Twelve young (Y, 4 years old) and 12 old (O, 11 years old) dogs, matched for body mass, were instrumented with left-ventricular pressure gauges, aortic and coronary sinus catheters, and flow probes on left circumflex artery. Before surgery, all dogs participated in a 6-wk exercise program. Dogs underwent measurements of hemodynamics and plasma substrates before and during a 2-h hyperinsulinemic-euglycemic clamp to measure whole body and myocardial glucose and nonesterified fatty acid uptake. Following the protocol, myocardial and skeletal samples were obtained to measure components of the insulin-signaling cascade and mitochondrial structure. There was no difference in plasma glucose (Y, 90 +/- 4 mg/dl; O, 87 +/- 4 mg/dl), but old dogs had higher (P < 0.02) nonesterified fatty acids (Y, 384 +/- 48 micromol/l; O, 952 +/- 97 micromol/l) and plasma insulin (Y, 39 +/- 11 pmol/l; O, 108 +/- 18 pmol/l). Old dogs had impaired total body glucose disposition (Y, 11.5 +/- 1 mg x kg(-1) x min(-1); O, 8.0 +/- 0.5 mg x kg(-1) x min(-1); P < 0.05) and insulin-stimulated myocardial glucose uptake (Y, 3.5 +/- 0.3 mg x min(-1) x g(-1); O, 1.8 +/- 0.3 mg x min(-1) x g(-1); P < 0.05). The impaired insulin action was associated with altered insulin signaling and glucose transporter (GLUT4) translocation. There were myocardial mitochondrial structural changes observed in association with decreased expression of uncoupling protein-3. Aging is associated with both whole body and myocardial insulin resistance, independent of obesity and inactivity, but involving altered mitochondrial structure and impaired cellular insulin action. PMID- 17873029 TI - Nutritional cues control Pseudomonas aeruginosa multicellular behavior in cystic fibrosis sputum. AB - The sputum (mucus) layer of the cystic fibrosis (CF) lung is a complex substrate that provides Pseudomonas aeruginosa with carbon and energy to support high density growth during chronic colonization. Unfortunately, the CF lung sputum layer has been difficult to mimic in animal models of CF disease, and mechanistic studies of P. aeruginosa physiology during growth in CF sputum are hampered by its complexity. In this study, we performed chromatographic and enzymatic analyses of CF sputum to develop a defined, synthetic CF sputum medium (SCFM) that mimics the nutritional composition of CF sputum. Importantly, P. aeruginosa displays similar phenotypes during growth in CF sputum and in SCFM, including similar growth rates, gene expression profiles, carbon substrate preferences, and cell-cell signaling profiles. Using SCFM, we provide evidence that aromatic amino acids serve as nutritional cues that influence cell-cell signaling and antimicrobial activity of P. aeruginosa during growth in CF sputum. PMID- 17873030 TI - Structure and biological activities of beta toxin from Staphylococcus aureus. AB - Beta toxin is a neutral sphingomyelinase secreted by certain strains of Staphylococcus aureus. This virulence factor lyses erythrocytes in order to evade the host immune system as well as scavenge nutrients. The structure of beta toxin was determined at 2.4-A resolution using crystals that were merohedrally twinned. This structure is similar to that of the sphingomyelinases of Listeria ivanovii and Bacillus cereus. Beta toxin belongs to the DNase I folding superfamily; in addition to sphingomyelinases, the proteins most structurally related to beta toxin include human endonuclease HAP1, Escherichia coli endonuclease III, bovine pancreatic DNase I, and the endonuclease domain of TRAS1 from Bombyx mori. Our biological assays demonstrated for the first time that beta toxin kills proliferating human lymphocytes. Structure-directed active site mutations show that biological activities, including hemolysis and lymphotoxicity, are due to the sphingomyelinase activity of the enzyme. PMID- 17873031 TI - Diminished LcrV secretion attenuates Yersinia pseudotuberculosis virulence. AB - Many gram-negative bacterial pathogenicity factors that function beyond the outer membrane are secreted via a contact-dependent type III secretion system. Two types of substrates are predestined for this mode of secretion, namely, antihost effectors that are translocated directly into target cells and the translocators required for targeting of the effectors across the host cell membrane. N-terminal secretion signals are important for recognition of the protein cargo by the type III secretion machinery. Even though such signals are known for several effectors, a consensus signal sequence is not obvious. One of the translocators, LcrV, has been attributed other functions in addition to its role in translocation. These functions include regulation, presumably via interaction with LcrG inside bacteria, and immunomodulation via interaction with Toll-like receptor 2. Here we wanted to address the significance of the specific targeting of LcrV to the exterior for its function in regulation, effector targeting, and virulence. The results, highlighting key N-terminal amino acids important for LcrV secretion, allowed us to dissect the role of LcrV in regulation from that in effector targeting/virulence. While only low levels of exported LcrV were required for in vitro effector translocation, as deduced by a cell infection assay, fully functional export of LcrV was found to be a prerequisite for its role in virulence in the systemic murine infection model. PMID- 17873032 TI - Role for the RecBCD recombination pathway for pilE gene variation in repair proficient Neisseria gonorrhoeae. AB - The role of the RecBCD recombination pathway in PilE antigenic variation in Neisseria gonorrhoeae is contentious and appears to be strain dependent. In this study, N. gonorrhoeae strain MS11 recB mutants were assessed for recombination/repair. MS11 recB mutants were found to be highly susceptible to DNA treatments that caused double-chain breaks and were severely impaired for growth; recB growth suppressor mutants arose at high frequencies. When the recombination/repair capacity of strain MS11 was compared to that of strains FA1090 and P9, innate differences were observed between the strains, with FA1090 and P9 rec(+) bacteria presenting pronounced recombination/repair defects. Consequently, MS11 recB mutants present a more robust phenotype than the other strains that were tested. In addition, MS11 recB mutants are also shown to be defective for pilE/pilS recombination. Moreover, pilE/pilS recombination is shown to proceed with gonococci that carry inverted pilE loci. Consequently, a novel RecBCD-mediated double-chain-break repair model for PilE antigenic variation is proposed. PMID- 17873033 TI - Identification of harpins in Pseudomonas syringae pv. tomato DC3000, which are functionally similar to HrpK1 in promoting translocation of type III secretion system effectors. AB - Harpins are a subset of type III secretion system (T3SS) substrates found in all phytopathogenic bacteria that utilize a T3SS. Pseudomonas syringae pv. tomato DC3000 was previously reported to produce two harpins, HrpZ1 and HrpW1. DC3000 was shown here to deploy two additional proteins, HopAK1 and HopP1, which have the harpin-like properties of lacking cysteine, eliciting the hypersensitive response (HR) when partially purified and infiltrated into tobacco leaves, and possessing a two-domain structure similar to that of the HrpW1 class of harpins. Unlike the single-domain harpin HrpZ1, the two-domain harpins have C-terminal enzyme-like domains: pectate lyase for HopAK1 and lytic transglycosylase for HopP1. Genetic techniques to recycle antibiotic markers were applied to DC3000 to generate a quadruple harpin gene polymutant. The polymutant was moderately reduced in the elicitation of the HR and translocation of the T3SS effector AvrPto1 fused to a Cya translocation reporter, but the mutant was unaffected in the secretion of AvrPto1-Cya. The DC3000 hrpK1 gene encodes a putative translocator in the HrpF/NopX family and was deleted in combination with the four harpin genes. The hrpK1 quadruple harpin gene polymutant was strongly reduced in HR elicitation, virulence, and translocation of AvrPto1-Cya into plant cells but not in the secretion of representative T3SS substrates in culture. HrpK1, HrpZ1, HrpW1, and HopAK1, but not HopP1, were independently capable of restoring some HR elicitation to the hrpK1 quadruple harpin gene polymutant, which suggests that a consortium of semiredundant translocators from three protein classes cooperate to form the P. syringae T3SS translocon. PMID- 17873034 TI - A functional two-partner secretion system contributes to adhesion of Neisseria meningitidis to epithelial cells. AB - Neisseria meningitidis is a frequent commensal of the human nasopharynx causing severe invasive infections in rare cases. A functional two-partner secretion (TPS) system in N. meningitidis, composed of the secreted effector protein HrpA and its cognate transporter HrpB, is identified and characterized in this study. Although all meningococcal strains harbor at least one TPS system, the hrpA genes display significant C-terminal sequence variation. Meningococcal genes encoding the TPS effector proteins and their transporters are closely associated and transcribed into a single mRNA. HrpA proteins are translocated across the meningococcal outer membrane by their cognate transporters HrpB and mainly released into the environment. During this process, HrpA is proteolytically processed to a mature 180-kDa form. In contrast to other known TPS systems, immature HrpA proteins are stable in the absence of HrpB and accumulate within the bacterial cell. A small percentage of mature HrpA remains associated with the bacteria and contributes to the interaction of meningococci with epithelial cells. PMID- 17873035 TI - Flagella facilitate escape of Salmonella from oncotic macrophages. AB - The intracellular parasite Salmonella enterica serovar Typhimurium causes a typhoid-like systemic disease in mice. Whereas the survival of Salmonella in phagocytes is well understood, little has been documented about the exit of intracellular Salmonella from host cells. Here we report that in a population of infected macrophages Salmonella induces "oncosis," an irreversible progression to eukaryotic cell death characterized by swelling of the entire cell body. Oncotic macrophages (OnMphis) are terminal deoxynucleotidyltransferase-mediated dUTP biotin nick end labeling negative and lack actin filaments (F-actin). The plasma membrane of OnMphis filled with bacilli remains impermeable, and intracellular Salmonella bacilli move vigorously using flagella. Eventually, intracellular Salmonella bacilli intermittently exit host cells in a flagellum-dependent manner. These results suggest that induction of macrophage oncosis and intracellular accumulation of flagellated bacilli constitute a strategy whereby Salmonella escapes from host macrophages. PMID- 17873037 TI - The complete genome sequence of Campylobacter jejuni strain 81116 (NCTC11828). AB - Campylobacter jejuni is a major human enteric pathogen that displays genetic variability via genomic reorganization and phase variation. This variability can adversely affect the outcomes and reproducibility of experiments. C. jejuni strain 81116 (NCTC11828) has been suggested to be a genetically stable strain (G. Manning, B. Duim, T. Wassenaar, J. A. Wagenaar, A. Ridley, and D. G. Newell, Appl. Environ. Microbiol. 67:1185-1189, 2001), is amenable to genetic manipulation, and is infective for chickens. Here we report the finished annotated genome sequence of C. jejuni strain 81116. PMID- 17873036 TI - Phosphate-controlled regulator for the biosynthesis of the dalbavancin precursor A40926. AB - The actinomycete Nonomuraea sp. strain ATCC 39727 produces the glycopeptide A40926, the precursor of the novel antibiotic dalbavancin. Previous studies have shown that phosphate limitation results in enhanced A40926 production. The A40926 biosynthetic gene (dbv) cluster, which consists of 37 genes, encodes two putative regulators, Dbv3 and Dbv4, as well as the response regulator (Dbv6) and the sensor-kinase (Dbv22) of a putative two-component system. Reverse transcription PCR (RT-PCR) and real-time RT-PCR analysis revealed that the dbv14-dbv8 and the dbv30-dbv35 operons, as well as dbv4, were negatively influenced by phosphate. Dbv4 shows a putative helix-turn-helix DNA-binding motif and shares sequence similarity with StrR, the transcriptional activator of streptomycin biosynthesis in Streptomyces griseus. Dbv4 was expressed in Escherichia coli as an N-terminal His(6)-tagged protein. The purified protein bound the dbv14 and dbv30 upstream regions but not the region preceding dbv4. Bbr, a Dbv4 ortholog from the gene cluster for the synthesis of the glycopeptide balhimycin, also bound to the dbv14 and dbv30 upstream regions, while Dbv4 bound appropriate regions from the balhimycin cluster. Our results provide new insights into the regulation of glycopeptide antibiotics, indicating that the phosphate-controlled regulator Dbv4 governs two key steps in A40926 biosynthesis: the biosynthesis of the nonproteinogenic amino acid 3,5-dihydroxyphenylglycine and critical tailoring reactions on the heptapeptide backbone. PMID- 17873038 TI - Biofilm formation-gene expression relay system in Escherichia coli: modulation of sigmaS-dependent gene expression by the CsgD regulatory protein via sigmaS protein stabilization. AB - Bacteria can switch from a single-cell (planktonic) mode to a multicellular community (biofilm) mode via production of cell-cell aggregation and surface adhesion factors. In this report, we present evidence that the CsgD protein, a transcription regulator involved in biofilm formation in Escherichia coli, modulates the expression of the rpoS (sigma(S)) regulon. Protein pattern analysis of E. coli cells in stationary phase shows that CsgD affects the expression of several proteins encoded by sigma(S)-dependent genes. CsgD regulation of sigma(S) dependent genes takes place at gene transcription level, does not bypass the need for rpoS, and is abolished in an rpoS-null mutant. Consistent with these results, we find that CsgD expression leads to an increase in sigma(S) intracellular concentration. Increase in sigma(S) cellular amount is mediated by CsgD-dependent transcription activation of iraP, encoding a factor involved in sigma(S) protein stabilization. Our results strongly suggest that the CsgD regulatory protein plays a major role as a relay between adhesion factors production and sigma(S) dependent gene expression via sigma(S) protein stabilization. Direct coordination between biofilm formation and expression of the rpoS regulon could positively impact important biological processes, such as host colonization or response to environmental stresses. PMID- 17873039 TI - The Escherichia coli Yej transporter is required for the uptake of translation inhibitor microcin C. AB - Microcin C (McC), a peptide-nucleotide antibiotic, targets aspartyl-tRNA synthetase. By analyzing a random transposon library, we identified Escherichia coli mutants resistant to McC. Transposon insertions were localized to a single locus, yejABEF, which encodes components of a putative inner membrane ABC transporter. Analysis of site-specific mutants established that all four components of the transporter are required for McC sensitivity. Since aspartyl tRNA synthetase in yej mutant extracts was fully sensitive to McC, we conclude that yej mutations interfere with McC uptake and that YejABEF is the only inner membrane transporter responsible for McC uptake in E. coli. Other substrates of YejABEF remain to be identified. PMID- 17873041 TI - The flagellar muramidase from the photosynthetic bacterium Rhodobacter sphaeroides. AB - We have characterized open reading frame RSP0072, which is located within the flgG operon in Rhodobacter sphaeroides. The amino acid sequence analysis of this gene product showed the presence of a soluble lytic transglycosylase domain. The deletion of the N-terminal region (90 amino acids) of the product of RSP0072 yields a leaky nonmotile phenotype, as determined by swarm assays in soft agar. Electron micrographs revealed the lack of flagella in mutant cells. The purified wild-type protein showed lytic activity on extracts of Micrococcus luteus. In contrast, no lytic activity was observed when the residues E57 or E83 were replaced by alanine. Affinity blotting suggests that the protein encoded by RSP0072 interacts with the flagellar rod-scaffolding protein FlgJ, which lacks the muramidase domain present in FlgJ of many bacteria. We propose that the product of RSP0072 is a flagellar muramidase that is exported to the periplasm via the Sec pathway, where it interacts with FlgJ to open a gap in the peptidoglycan layer for the subsequent penetration of the nascent flagellar structure. PMID- 17873040 TI - In vivo DNA binding of bacteriophage GA-1 protein p6. AB - Bacteriophage GA-1 infects Bacillus sp. strain G1R and has a linear double stranded DNA genome with a terminal protein covalently linked to its 5' ends. GA 1 protein p6 is very abundant in infected cells and binds DNA with no sequence specificity. We show here that it binds in vivo to the whole viral genome, as detected by cross-linking, chromatin immunoprecipitation, and real-time PCR analyses, and has the characteristics of a histone-like protein. Binding to DNA of GA-1 protein p6 shows little supercoiling dependency, in contrast to the ortholog protein of the evolutionary related Bacillus subtilis phage phi29. This feature is a property of the protein rather than the DNA or the cellular background, since phi29 protein p6 shows supercoiling-dependent binding to GA-1 DNA in Bacillus sp. strain G1R. GA-1 DNA replication is impaired in the presence of the gyrase inhibitors novobiocin and nalidixic acid, which indicates that, although noncovalently closed, the viral genome is topologically constrained in vivo. GA-1 protein p6 is also able to bind phi29 DNA in B. subtilis cells; however, as expected, the binding is less supercoiling dependent than the one observed with the phi29 protein p6. In addition, the nucleoprotein complex formed is not functional, since it is not able to transcomplement the DNA replication deficiency of a phi29 sus6 mutant. Furthermore, we took advantage of phi29 protein p6 binding to GA-1 DNA to find that the viral DNA ejection mechanism seems to take place, as in the case of phi29, with a right to left polarity in a two-step, push-pull process. PMID- 17873042 TI - Distribution, functional expression, and genetic organization of Cif, a phage encoded type III-secreted effector from enteropathogenic and enterohemorrhagic Escherichia coli. AB - Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) inject effector proteins into host cells via a type III secretion system encoded by the locus of enterocyte effacement (LEE). One of these effectors is Cif, encoded outside the LEE by a lambdoid prophage. In this study, we demonstrated that the Cif-encoding prophage of EPEC strain E22 is inducible and produces infectious phage particles. We investigated the distribution and functional expression of Cif in 5,049 E. coli strains of human, animal, and environmental origins. A total of 115 E. coli isolates from diverse origins and geographic locations carried cif. The presence of cif was tightly associated with the LEE, since all the cif-positive isolates were positive for the LEE. These results suggested that the Cif-encoding prophages have been widely disseminated within the natural population of E. coli but positively selected within the population of LEE-positive strains. Nonetheless, 66% of cif-positive E. coli strains did not induce a typical Cif-related phenotype in eukaryotic cells due to frameshift mutations or insertion of an IS element in the cif gene. The passenger region of the prophages carrying cif was highly variable and showed various combinations of IS elements and genes coding for other effectors such as nleB, nleC, nleH, nleG, espJ, and nleA/espI (some of which were also truncated). This diversity and the presence of nonfunctional effectors should be taken into account to assess EPEC and EHEC pathogenicity and tropism. PMID- 17873043 TI - Five genes encoding surface-exposed LPXTG proteins are enriched in hospital adapted Enterococcus faecium clonal complex 17 isolates. AB - Most Enterococcus faecium isolates associated with hospital outbreaks and invasive infections belong to a distinct genetic subpopulation called clonal complex 17 (CC17). It has been postulated that the genetic evolution of CC17 involves the acquisition of various genes involved in antibiotic resistance, metabolic pathways, and virulence. To gain insight into additional genes that may have favored the rapid emergence of this nosocomial pathogen, we aimed to identify surface-exposed LPXTG cell wall-anchored proteins (CWAPs) specifically enriched in CC17 E. faecium. Using PCR and Southern and dot blot hybridizations, 131 E. faecium isolates (40 CC17 and 91 non-CC17) were screened for the presence of 22 putative CWAP genes identified from the E. faecium TX0016 genome. Five genes encoding LPXTG surface proteins were specifically enriched in E. faecium CC17 isolates. These five LPXTG surface protein genes were found in 28 to 40 (70 to 100%) of CC17 and in only 7 to 24 (8 to 26%) of non-CC17 isolates (P < 0.05). Three of these CWAP genes clustered together on the E. faecium TX0016 genome, which may comprise a novel enterococcal pathogenicity island covering E. faecium contig 609. Expression at the mRNA level was demonstrated, and immunotransmission electron microscopy revealed an association of the five LPXTG surface proteins with the cell wall. Minimal spanning tree analysis based on the presence and absence of 22 CWAP genes revealed grouping of all 40 CC17 strains together with 18 hospital-derived but evolutionary unrelated non-CC17 isolates in a distinct CWAP-enriched cluster, suggesting horizontal transfer of CWAP genes and a role of these CWAPs in hospital adaptation. PMID- 17873044 TI - Computational prediction and experimental verification of the gene encoding the NAD+/NADP+-dependent succinate semialdehyde dehydrogenase in Escherichia coli. AB - Although NAD(+)-dependent succinate semialdehyde dehydrogenase activity was first described in Escherichia coli more than 25 years ago, the responsible gene has remained elusive so far. As an experimental proof of concept for a gap-filling algorithm for metabolic networks developed earlier, we demonstrate here that the E. coli gene yneI is responsible for this activity. Our biochemical results demonstrate that the yneI-encoded succinate semialdehyde dehydrogenase can use either NAD(+) or NADP(+) to oxidize succinate semialdehyde to succinate. The gene is induced by succinate semialdehyde, and expression data indicate that yneI plays a unique physiological role in the general nitrogen metabolism of E. coli. In particular, we demonstrate using mutant growth experiments that the yneI gene has an important, but not essential, role during growth on arginine and probably has an essential function during growth on putrescine as the nitrogen source. The NADP(+)-dependent succinate semialdehyde dehydrogenase activity encoded by the functional homolog gabD appears to be important for nitrogen metabolism under N limitation conditions. The yneI-encoded activity, in contrast, functions primarily as a valve to prevent toxic accumulation of succinate semialdehyde. Analysis of available genome sequences demonstrated that orthologs of both yneI and gabD are broadly distributed across phylogenetic space. PMID- 17873045 TI - Thioredoxin reductase is essential for thiol/disulfide redox control and oxidative stress survival of the anaerobe Bacteroides fragilis. AB - Results of this study showed that the anaerobic, opportunistic pathogen Bacteroides fragilis lacks the glutathione/glutaredoxin redox system and possesses an extensive number of putative thioredoxin (Trx) orthologs. Analysis of the genome sequence revealed six Trx orthologs and an absence of genes required for synthesis of glutathione and glutaredoxins. In addition, it was shown that the thioredoxin reductase (TrxB)/Trx system is the major or sole redox system for thiol/disulfide cellular homeostasis in this anaerobic bacterium. Expression of the B. fragilis trxB gene was induced following treatment with diamide or H(2)O(2) or exposure to oxygen. This inducible trxB expression was OxyR independent. Northern blot hybridization analysis showed that the trxB mRNA was cotranscribed with lolA as a bicistronic transcript or was present as a monocistronic transcript that was also highly induced under the same conditions. The role of LolA, a prokaryotic periplasmic lipoprotein-specific molecular chaperone in the thiol/disulfide redox system, is unknown. A trxB deletion mutant was more sensitive to the effects of diamide and oxygen than the parent strain. In addition, the trxB mutant was unable to grow in culture media without addition of a reductant. Furthermore, the trxB mutant was not able to induce intraabdominal abscess formation in a mouse model, whereas the parent strain was. Taken together, these data strongly suggest that TrxB/Trx is the major, if not the sole, thiol/disulfide redox system in this anaerobe required for survival and abscess formation in a peritoneal cavity infection model. PMID- 17873046 TI - Iteron-binding ORF157 and FtsZ-like ORF156 proteins encoded by pBtoxis play a role in its replication in Bacillus thuringiensis subsp. israelensis. AB - We recently identified a minireplicon of pBtoxis from Bacillus thuringiensis subsp. israelensis that contained an operon encoding two novel proteins (ORF156 and ORF157), both of which are required for replication. ORF157 contains a helix turn-helix motif and shares no homology with known plasmid replication proteins (Rep), and ORF156 contains the signature motif present in FtsZ/tubulin proteins, the latter of which are known to function in cell division and chromosome segregation. Here we show that the minimal sequence composed of four 12-bp imperfect direct repeats (iterons) in the pBtoxis minireplicon was sufficient to replicate a reporter plasmid in B. thuringiensis subsp. israelensis when ORF156 and ORF157 functions were provided in trans. To further investigate the roles of ORF156 and ORF157 in pBtoxis replication, six-histidine-tagged recombinant rORF156 and rORF157 proteins were purified from Escherichia coli and used in electrophoretic mobility shift assays. Our results demonstrated that rORF157, but not rORF156, binds specifically to the pBtoxis iterons, suggesting that ORF157 functions as a Rep protein. Although rORF156 did not bind to the iteron sequence, we showed that it bound to rORF157-DNA complexes. In addition, we showed that rORF156 has GTPase activity characteristic of the FtsZ/tubulin superfamily of proteins. Taken together, these results suggest that the iterons compose the minimal replication origin (ori) of pBtoxis and that ORF157 and ORF156 are involved in the initiation of pBtoxis replication and possibly in the segregation and partitioning of this plasmid to daughter cells. PMID- 17873047 TI - Evidence that bacterial ABC-type transporter imports free EDTA for metabolism. AB - EDTA, a common chelating agent, is becoming a major organic pollutant in the form of metal-EDTA complexes in surface waters, partly due to its recalcitrance to biodegradation. Even an EDTA-degrading bacterium, BNC1, does not degrade stable metal-EDTA complexes. In the present study, an ABC-type transporter was identified for possible uptake of EDTA because the transporter genes and the EDTA monooxygenase gene were expressed from a single operon in BNC1. The ABC-type transporter had a periplasmic-binding protein (EppA) that should confer the substrate specificity for the transporter; therefore, EppA was produced in Escherichia coli, purified, and characterized. EppA was shown to bind free EDTA with a dissociation constant as low as 25 nM by using isothermal titration calorimetry. When unstable metal-EDTA complexes, e.g., (Mg-EDTA)(2-), were added to the EppA solution, binding was also observed. However, experimental data and theoretical analysis supported EppA binding only of free EDTA. When stable metal EDTA complexes, e.g., (Cu-EDTA)(2-), were titrated into the EppA solution, no binding was observed. Since EDTA monooxygenase in the cytoplasm uses some of the stable metal-EDTA complexes as substrates, we suggest that the lack of EppA binding and EDTA uptake are responsible for the failure of BNC1 cells to degrade the stable complexes. PMID- 17873048 TI - Identification of a Vibrio furnissii oligopeptide permease and characterization of its in vitro hemolytic activity. AB - We describe purification and characterization of an oligopeptide permease protein (Hly-OppA) from Vibrio furnissii that has multifaceted functions in solute binding, in in vitro hemolysis, in antibiotic resistance, and as a virulence factor in bacterial pathogenesis. The solute-binding function was revealed by N terminal and internal peptide sequences of the purified protein and was confirmed by discernible effects on oligopeptide binding, by accumulation of fluorescent substrates, and by fluorescent substrate-antibiotic competition assay experiments. The purified protein exhibited host-specific in vitro hemolytic activity against various mammalian erythrocytes and apparent cytotoxicity in CHO K1 cells. Recombinant Hly-OppA protein and an anti-Hly-OppA monoclonal antibody exhibited and neutralized the in vitro hemolytic activity, respectively, which further confirmed the hemolytic activity of the gene product. In addition, a V. furnissii hly-oppA knockout mutant caused less mortality than the wild-type strain when it was inoculated into BALB/c mice, indicating the virulence function of this protein. Finally, the in vitro hemolytic activity was also confirmed with homologous ATP-binding cassette-type transporter proteins from other Vibrio species. PMID- 17873049 TI - Control of cell wall assembly by a histone-like protein in Mycobacteria. AB - Bacteria coordinate assembly of the cell wall as well as synthesis of cellular components depending on the growth state. The mycobacterial cell wall is dominated by mycolic acids covalently linked to sugars, such as trehalose and arabinose, and is critical for pathogenesis of mycobacteria. Transfer of mycolic acids to sugars is necessary for cell wall biogenesis and is mediated by mycolyltransferases, which have been previously identified as three antigen 85 (Ag85) complex proteins. However, the regulation mechanism which links cell wall biogenesis and the growth state has not been elucidated. Here we found that a histone-like protein has a dual concentration-dependent regulatory effect on mycolyltransferase functions of the Ag85 complex through direct binding to both the Ag85 complex and the substrate, trehalose-6-monomycolate, in the cell wall. A histone-like protein-deficient Mycobacterium smegmatis strain has an unusual crenellated cell wall structure and exhibits impaired cessation of glycolipid biosynthesis in the growth-retarded phase. Furthermore, we found that artificial alteration of the amount of the extracellular histone-like protein and the Ag85 complex changes the growth rate of mycobacteria, perhaps due to impaired down regulation of glycolipid biosynthesis. Our results demonstrate novel regulation of cell wall assembly which has an impact on bacterial growth. PMID- 17873050 TI - Phosphopantetheine adenylyltransferase from Escherichia coli: investigation of the kinetic mechanism and role in regulation of coenzyme A biosynthesis. AB - Phosphopantetheine adenylyltransferase (PPAT) from Escherichia coli is an essential hexameric enzyme that catalyzes the penultimate step in coenzyme A (CoA) biosynthesis and is a target for antibacterial drug discovery. The enzyme utilizes Mg-ATP and phosphopantetheine (PhP) to generate dephospho-CoA (dPCoA) and pyrophosphate. When overexpressed in E. coli, PPAT copurifies with tightly bound CoA, suggesting a feedback inhibitory role for this cofactor. Using an enzyme-coupled assay for the forward-direction reaction (dPCoA-generating) and isothermal titration calorimetry, we investigated the steady-state kinetics and ligand binding properties of PPAT. All substrates and products bind the free enzyme, and product inhibition studies are consistent with a random bi-bi kinetic mechanism. CoA inhibits PPAT and is competitive with ATP, PhP, and dPCoA. Previously published structures of PPAT crystallized at pH 5.0 show half-the sites reactivity for PhP and dPCoA and full occupancy by ATP and CoA. Ligand binding studies at pH 8.0 show that ATP, PhP, dPCoA, and CoA occupy all six monomers of the PPAT hexamer, although CoA exhibits two thermodynamically distinct binding modes. These results suggest that the half-the-sites reactivity observed in PPAT crystal structures may be pH dependent. In light of previous studies on the regulation of CoA biosynthesis, the PPAT kinetic and ligand binding data suggest that intracellular PhP concentrations modulate the distribution of PPAT monomers between high- and low-affinity CoA binding modes. This model is consistent with PPAT serving as a "backup" regulator of pathway flux relative to pantothenate kinase. PMID- 17873051 TI - Dissection of the caffeate respiratory chain in the acetogen Acetobacterium woodii: identification of an Rnf-type NADH dehydrogenase as a potential coupling site. AB - The anaerobic acetogenic bacterium Acetobacterium woodii couples caffeate reduction with electrons derived from hydrogen to the synthesis of ATP by a chemiosmotic mechanism with sodium ions as coupling ions, a process referred to as caffeate respiration. We addressed the nature of the hitherto unknown enzymatic activities involved in this process and their cellular localization. Cell extract of A. woodii catalyzes H(2)-dependent caffeate reduction. This reaction is strictly ATP dependent but can be activated also by acetyl coenzyme A (CoA), indicating that there is formation of caffeyl-CoA prior to reduction. Two dimensional gel electrophoresis revealed proteins present only in caffeate-grown cells. Two proteins were identified by electrospray ionization-mass spectrometry/mass spectrometry, and the encoding genes were cloned. These proteins are very similar to subunits alpha (EtfA) and beta (EtfB) of electron transfer flavoproteins present in various anaerobic bacteria. Western blot analysis demonstrated that they are induced by caffeate and localized in the cytoplasm. Etf proteins are known electron carriers that shuttle electrons from NADH to different acceptors. Indeed, NADH was used as an electron donor for cytosolic caffeate reduction. Since the hydrogenase was soluble and used ferredoxin as an electron acceptor, the missing link was a ferredoxin:NAD(+) oxidoreductase. This activity could be determined and, interestingly, was membrane bound. A search for genes that could encode this activity revealed DNA fragments encoding subunits C and D of a membrane-bound Rnf-type NADH dehydrogenase that is a potential Na(+) pump. These data suggest the following electron transport chain: H(2) --> ferredoxin --> NAD(+) --> Etf --> caffeyl-CoA reductase. They also imply that the sodium motive step in the chain is the ferredoxin-dependent NAD(+) reduction catalyzed by Rnf. PMID- 17873052 TI - Sigma factor genes sigC, sigE, and sigG are upregulated in heterocysts of the cyanobacterium Anabaena sp. strain PCC 7120. AB - We used gfp transcriptional fusions to investigate the regulation of eight sigma factor genes during heterocyst development in the cyanobacterium Anabaena sp. strain PCC 7120. Reporter strains containing gfp fusions with the upstream regions of sigB2, sigD, sigI, and sigJ did not show developmental regulation. Time-lapse microscopy of sigC, sigE, and sigG reporter strains showed increased green fluorescent protein fluorescence in differentiating cells at 4 h, 16 h, and 9 h, respectively, after nitrogen step down. PMID- 17873053 TI - Regulation of expression of the fibronectin-binding protein BBK32 in Borrelia burgdorferi. AB - The BBK32 protein binds to host extracellular ligand fibronectin and contributes to the pathogenesis of Borrelia burgdorferi. Here we showed that expression of the BBK32 gene is influenced by multiple environmental factors and that its regulation is governed by the response regulator Rrp2 and RpoN-RpoS (sigma(54) sigma(S)) sigma cascade in B. burgdorferi. PMID- 17873054 TI - Array-based genomic comparative hybridization analysis of field strains of Mycoplasma hyopneumoniae. AB - Mycoplasma hyopneumoniae is the causative agent of porcine enzootic pneumonia and a major factor in the porcine respiratory disease complex. A clear understanding of the mechanisms of pathogenesis does not exist, although it is clear that M. hyopneumoniae adheres to porcine ciliated epithelium by action of a protein called P97. Previous studies have shown variation in the gene encoding the P97 cilium adhesin in different strains of M. hyopneumoniae, but the extent of genetic variation among field strains across the genome is not known. Since M. hyopneumoniae is a worldwide problem, it is reasonable to expect that a wide range of genetic variability may exist given all of the different breeds and housing conditions. This variation may impact the overall virulence of a single strain. Using microarray technology, this study examined the potential variation of 14 field strains compared to strain 232, on which the array was based. Genomic DNA was obtained, amplified with TempliPhi, and labeled indirectly with Alexa dyes. After genomic hybridization, the arrays were scanned and data were analyzed using a linear statistical model. The results indicated that genetic variation could be detected in all 14 field strains but across different loci, suggesting that variation occurs throughout the genome. Fifty-nine percent of the variable loci were hypothetical genes. Twenty-two percent of the lipoprotein genes showed variation in at least one field strain. A permutation test identified a location in the M. hyopneumoniae genome where there is spatial clustering of variability between the field strains and strain 232. PMID- 17873055 TI - The division inhibitor EzrA contains a seven-residue patch required for maintaining the dynamic nature of the medial FtsZ ring. AB - The essential cytoskeletal protein FtsZ assembles into a ring-like structure at the nascent division site and serves as a scaffold for the assembly of the prokaryotic division machinery. We previously characterized EzrA as an inhibitor of FtsZ assembly in Bacillus subtilis. EzrA interacts directly with FtsZ to prevent aberrant FtsZ assembly and cytokinesis at cell poles. EzrA also concentrates at the cytokinetic ring in an FtsZ-dependent manner, although its precise role at this position is not known. Here, we identified a conserved patch of amino acids in the EzrA C terminus that is essential for localization to the FtsZ ring. Mutations in this patch (designated the "QNR patch") abolish EzrA localization to midcell but do not significantly affect EzrA's ability to inhibit FtsZ assembly at cell poles. ezrA QNR patch mutant cells exhibit stabilized FtsZ assembly at midcell and are significantly longer than wild-type cells, despite lacking extra FtsZ rings. These results indicate that EzrA has two distinct activities in vivo: (i) preventing aberrant FtsZ ring formation at cell poles through inhibition of de novo FtsZ assembly and (ii) maintaining proper FtsZ assembly dynamics within the medial FtsZ ring, thereby rendering it sensitive to the factors responsible for coordinating cell growth and cell division. PMID- 17873057 TI - Work and peak torque during eccentric exercise do not predict changes in markers of muscle damage. AB - OBJECTIVES: Large inter-subject variability in responses to eccentric exercise has been reported. This study investigated the hypothesis that the variability of changes in indirect markers of exercise-induced muscle damage (EIMD) would be explained by work performed and/or torque generated during eccentric exercise. METHODS: Subjects (n = 53) performed 60 maximal eccentric actions of the elbow flexors on an isokinetic dynamometer that forcibly extended the elbow joint from 60 degrees to 180 degrees at a constant velocity (90 degrees s(-1)). Markers of EIMD included maximal voluntary isometric contraction torque at 90 degrees elbow flexion (MVC), range of motion, plasma creatine kinase activity and muscle soreness. Measurements were taken 2 days before, immediately after and 1-4 days post-exercise. Pearson's correlation coefficient was used to examine relationships between exercise parameters (total work, change in total work, torque produced during exercise, change in peak torque) and markers of EIMD. RESULTS: Large inter-subject variability was evident for both work and torque during exercise, and changes in all markers of EIMD. Contrary to the hypothesis, total work (normalised for individual pre-exercise MVC) did not correlate significantly with any markers of EIMD, with the exception of MVC (r = 0.3). Total work performed and changes in total work showed higher correlations with some markers, but no r-values exceeded 0.4. Normalised exercise torque and the changes in peak torque during exercise were not correlated with changes in MVC, or other markers. CONCLUSION: These results suggest the large inter-subject variability in responses to eccentric exercise is not associated with work performed or torque generated during eccentric exercise. PMID- 17873058 TI - Protein pyrophosphorylation by inositol pyrophosphates is a posttranslational event. AB - In a previous study, we showed that the inositol pyrophosphate diphosphoinositol pentakisphosphate (IP(7)) physiologically phosphorylates mammalian and yeast proteins. We now report that this phosphate transfer reflects pyrophosphorylation. Thus, proteins must be prephosphorylated by ATP to prime them for IP(7) phosphorylation. IP(7) phosphorylates synthetic phosphopeptides but not if their phosphates have been masked by methylation or pyrophosphorylation. Moreover, IP(7) phosphorylated peptides are more acid-labile and more resistant to phosphatases than ATP phosphorylated peptides, indicating a different type of phosphate bond. Pyrophosphorylation may represent a novel mode of signaling to proteins. PMID- 17873059 TI - Dmbx1 is essential in agouti-related protein action. AB - Dmbx1 is a paired-class homeodomain transcription factor. We show here that mice deficient in Dmbx1 exhibit severe leanness associated with hypophagia and hyperactivity and that isolation of a Dmbx1(-/-) mouse from its cohabitants induces self-starvation, sometimes leading to death, features similar to those of anorexia nervosa in humans. Interestingly, overexpression of agouti in Dmbx1(-/-) mice failed to induce aspects of the A(y)/a phenotype, including hyperphagia, obesity, and diabetes mellitus. In Dmbx1(-/-) mice, administration of agouti related protein increased cumulative food intake for the initial 6 h but significantly decreased it over 24- and 48-h periods. In addition, Dmbx1 was shown to be expressed at embryonic day 15.5 in the lateral parabrachial nucleus, the rostral nucleus of the tractus solitarius, the dorsal motor nucleus of the vagus, and the reticular nucleus in the brainstem, all of which receive melanocortin signaling, indicating involvement of Dmbx1 in the development of the neural network for the signaling. Thus, Dmbx1 is essential for various actions of agouti-related protein and plays a role in normal regulation of energy homeostasis and behavior. PMID- 17873060 TI - Crystallographic trapping in the rebeccamycin biosynthetic enzyme RebC. AB - The biosynthesis of rebeccamycin, an antitumor compound, involves the remarkable eight-electron oxidation of chlorinated chromopyrrolic acid. Although one rebeccamycin biosynthetic enzyme is capable of generating low levels of the eight electron oxidation product on its own, a second protein, RebC, is required to accelerate product formation and eliminate side reactions. However, the mode of action of RebC was largely unknown. Using crystallography, we have determined a likely function for RebC as a flavin hydroxylase, captured two snapshots of its dynamic catalytic cycle, and trapped a reactive molecule, a putative substrate, in its binding pocket. These studies strongly suggest that the role of RebC is to sequester a reactive intermediate produced by its partner protein and to react with it enzymatically, preventing its conversion to a suite of degradation products that includes, at low levels, the desired product. PMID- 17873061 TI - Processing and function of CFTR-DeltaF508 are species-dependent. AB - Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis. The most common mutation, a deletion of the phenylalanine at position 508 (DeltaF508), disrupts processing of the protein. Nearly all human CFTR-DeltaF508 is retained in the endoplasmic reticulum and degraded, preventing maturation to the plasma membrane. In addition, the F508 deletion reduces the activity of single CFTR channels. Human CFTR-DeltaF508 has been extensively studied to better understand its defects. Here, we adopted a cross-species comparative approach, examining human, pig, and mouse CFTR-DeltaF508. As with human CFTR-DeltaF508, the DeltaF508 mutation reduced the single-channel activity of the pig and mouse channels. However, the mutant pig and mouse proteins were at least partially processed like their wild-type counterparts. Moreover, pig and mouse CFTR-DeltaF508 partially restored transepithelial Cl(-) transport to CF airway epithelia. Our data, combined with earlier work, suggest that there is a gradient in the severity of the CFTR-DeltaF508 processing defect, with human more severe than pig or mouse. These findings may explain some previously puzzling observations in CF mice, they have important implications for evaluation of potential therapeutics, and they suggest new strategies for discovering the mechanisms that disrupt processing of human CFTR-DeltaF508. PMID- 17873062 TI - Type VI secretion system translocates a phage tail spike-like protein into target cells where it cross-links actin. AB - Genes encoding type VI secretion systems (T6SS) are widely distributed in pathogenic Gram-negative bacterial species. In Vibrio cholerae, T6SS have been found to secrete three related proteins extracellularly, VgrG-1, VgrG-2, and VgrG 3. VgrG-1 can covalently cross-link actin in vitro, and this activity was used to demonstrate that V. cholerae can translocate VgrG-1 into macrophages by a T6SS dependent mechanism. Protein structure search algorithms predict that VgrG related proteins likely assemble into a trimeric complex that is analogous to that formed by the two trimeric proteins gp27 and gp5 that make up the baseplate "tail spike" of Escherichia coli bacteriophage T4. VgrG-1 was shown to interact with itself, VgrG-2, and VgrG-3, suggesting that such a complex does form. Because the phage tail spike protein complex acts as a membrane-penetrating structure as well as a conduit for the passage of DNA into phage-infected cells, we propose that the VgrG components of the T6SS apparatus may assemble a "cell puncturing device" analogous to phage tail spikes to deliver effector protein domains through membranes of target host cells. PMID- 17873063 TI - Plasmodium falciparum ookinetes require mosquito midgut chondroitin sulfate proteoglycans for cell invasion. AB - Malaria transmission entails development of the Plasmodium parasite in its insect vector, the Anopheles mosquito. Parasite invasion of the mosquito midgut is the critical first step and involves adhesion to host epithelial cell ligands. Partial evidence suggests that midgut oligosaccharides are important ligands for parasite adhesion; however, the identity of these glycans remains unknown. We have identified a population of chondroitin glycosaminoglycans along the apical midgut microvilli of Anopheles gambiae and further demonstrated ookinete recognition of these glycans in vitro. By repressing the expression of the peptide-O-xylosyltransferase homolog of An. gambiae by means of RNA interference, we blocked glycosaminoglycan chain biosynthesis, diminished chondroitin sulfate levels in the adult midgut, and substantially inhibited parasite development. We provide evidence for the in vivo role of chondroitin sulfate proteoglycans in Plasmodium falciparum invasion of the midgut and insight into the molecular mechanisms mediating parasite-mosquito interactions. PMID- 17873064 TI - Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance. AB - Long-term allograft survival generally requires lifelong immunosuppression (IS). Rarely, recipients display spontaneous "operational tolerance" with stable graft function in the absence of IS. The lack of biological markers of this phenomenon precludes identification of potentially tolerant patients in which IS could be tapered and hinders the development of new tolerance-inducing strategies. The objective of this study was to identify minimally invasive blood biomarkers for operational tolerance and use these biomarkers to determine the frequency of this state in immunosuppressed patients with stable graft function. Blood gene expression profiles from 75 renal-transplant patient cohorts (operational tolerance/acute and chronic rejection/stable graft function on IS) and 16 healthy individuals were analyzed. A subset of samples was used for microarray analysis where three-class comparison of the different groups of patients identified a "tolerant footprint" of 49 genes. These biomarkers were applied for prediction of operational tolerance by microarray and real-time PCR in independent test groups. Thirty-three of 49 genes correctly segregated tolerance and chronic rejection phenotypes with 99% and 86% specificity. The signature is shared with 1 of 12 and 5 of 10 stable patients on triple IS and low-dose steroid monotherapy, respectively. The gene signature suggests a pattern of reduced costimulatory signaling, immune quiescence, apoptosis, and memory T cell responses. This study identifies in the blood of kidney recipients a set of genes associated with operational tolerance that may have utility as a minimally invasive monitoring tool for guiding IS titration. Further validation of this tool for safe IS minimization in prospective clinical trials is warranted. PMID- 17873065 TI - Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation. AB - TLX is a transcription factor that is essential for neural stem cell proliferation and self-renewal. However, the molecular mechanism of TLX-mediated neural stem cell proliferation and self-renewal is largely unknown. We show here that TLX recruits histone deacetylases (HDACs) to its downstream target genes to repress their transcription, which in turn regulates neural stem cell proliferation. TLX interacts with HDAC3 and HDAC5 in neural stem cells. The HDAC5 interaction domain was mapped to TLX residues 359-385, which contains a conserved nuclear receptor-coregulator interaction motif IXXLL. Both HDAC3 and HDAC5 have been shown to be recruited to the promoters of TLX target genes along with TLX in neural stem cells. Recruitment of HDACs led to transcriptional repression of TLX target genes, the cyclin-dependent kinase inhibitor, p21(CIP1/WAF1)(p21), and the tumor suppressor gene, pten. Either inhibition of HDAC activity or knockdown of HDAC expression led to marked induction of p21 and pten gene expression and dramatically reduced neural stem cell proliferation, suggesting that the TLX interacting HDACs play an important role in neural stem cell proliferation. Moreover, expression of a TLX peptide containing the minimal HDAC5 interaction domain disrupted the TLX-HDAC5 interaction. Disruption of this interaction led to significant induction of p21 and pten gene expression and to dramatic inhibition of neural stem cell proliferation. Taken together, these findings demonstrate a mechanism for neural stem cell proliferation through transcriptional repression of p21 and pten gene expression by TLX-HDAC interactions. PMID- 17873066 TI - Climate and on-farm risk factors associated with Giardia duodenalis cysts in storm runoff from California coastal dairies. AB - Climatic factors and on-farm management practices were evaluated for their association with the concentrations (cyst/liter) and instantaneous loads (cysts/second) of Giardia duodenalis in storm-based runoff from dairy lots and other high-cattle-use areas on five coastal California farms over two storm seasons. Direct fluorescent antibody analysis was used to quantitate cysts in 350 storm runoff samples. G. duodenalis was detected on all five dairy farms, with fluxes of 1 to 14,000 cysts/liter observed in 16% of samples. Cysts were detected in 41% of runoff samples collected near cattle less than 2 months old, compared to 10% of runoff samples collected near cattle over 6 months old. Furthermore, the concentrations and instantaneous loads of cysts were > or =65 and > or =79 times greater, respectively, in runoff from sites housing young calves than in sites housing other age classes of animals. Factors associated with environmental loading of G. duodenalis included cattle age, cattle stocking number, and precipitation but not lot area, land slope, or cattle density. Vegetated buffer strips were found to significantly reduce waterborne cysts in storm runoff: each additional meter of vegetated buffer placed below high-cattle-use areas was associated with reductions in the concentration and instantaneous load of cysts by factors of 0.86 and 0.79 (-0.07 and -0.10 log(10)/m), respectively. Straw mulch, seed application, scraping of manure, and cattle exclusion did not significantly affect the concentration or load of G. duodenalis cysts. The study findings suggest that vegetated buffer strips, especially when placed near dairy calf areas, should help reduce the environmental loading of these fecal protozoa discharging from dairy farms. PMID- 17873068 TI - Genetic method to analyze essential genes of Escherichia coli. AB - The genetic analysis of essential genes has been generally restricted to the use of conditional mutations, or inactivating chromosomal mutations, which require a complementing plasmid that must either be counterselected or lost to measure a phenotype. These approaches are limited because they do not permit the analysis of mutations suspected to affect a specific function of a protein, nor do they take advantage of the increasing abundance of structural and bioinformatics data for proteins. Using the dnaC gene as an example, we developed a genetic method that should permit the mutational analysis of other essential genes of Escherichia coli and related enterobacteria. The method consists of using a strain carrying a large deletion of the dnaC gene, which is complemented by a wild-type copy expressed from a plasmid that requires isopropyl-beta-d thiogalactopyranoside for maintenance. Under conditions in which this resident plasmid is lost, the method measures the function of a dnaC mutation encoded by a second plasmid. This methodology should be widely applicable to the genetic analysis of other essential genes. PMID- 17873067 TI - Regulation of a novel Acidithiobacillus caldus gene cluster involved in metabolism of reduced inorganic sulfur compounds. AB - Acidithiobacillus caldus has been proposed to play a role in the oxidation of reduced inorganic sulfur compounds (RISCs) produced in industrial biomining of sulfidic minerals. Here, we describe the regulation of a new cluster containing the gene encoding tetrathionate hydrolase (tetH), a key enzyme in the RISC metabolism of this bacterium. The cluster contains five cotranscribed genes, ISac1, rsrR, rsrS, tetH, and doxD, coding for a transposase, a two-component response regulator (RsrR and RsrS), tetrathionate hydrolase, and DoxD, respectively. As shown by quantitative PCR, rsrR, tetH, and doxD are upregulated to different degrees in the presence of tetrathionate. Western blot analysis also indicates upregulation of TetH in the presence of tetrathionate, thiosulfate, and pyrite. The tetH cluster is predicted to have two promoters, both of which are functional in Escherichia coli and one of which was mapped by primer extension. A pyrrolo-quinoline quinone binding domain in TetH was predicted by bioinformatic analysis, and the presence of an o-quinone moiety was experimentally verified, suggesting a mechanism for tetrathionate oxidation. PMID- 17873069 TI - Acanthamoeba-Campylobacter coculture as a novel method for enrichment of Campylobacter species. AB - In this study, we present a novel method to isolate and enrich low concentrations of Campylobacter pathogens. This method, Acanthamoeba-Campylobacter coculture (ACC), is based on the intracellular survival and multiplication of Campylobacter species in the free-living protozoan Acanthamoeba polyphaga. Four of the Campylobacter species relevant to humans and livestock, Campylobacter jejuni, C. coli, C. lari, and C. hyointestinalis, were effectively enriched by the coculture method, with growth rates comparable to those observed in other Campylobacter enrichment media. Studying six strains of C. jejuni isolated from different sources, we found that all of the strains could be enriched from an inoculum of fewer than 10 bacteria. The sensitivity of the ACC method was not negatively affected by the use of Campylobacter-selective antibiotics in the culture medium, but these were effective in suppressing the growth of seven different bacterial species added at a concentration of 10(4) CFU/ml of each species as deliberate contamination. The ACC method has advantages over other enrichment methods as it is not dependent on a microaerobic milieu and does not require the use of blood or other oxygen-quenching agents. Our study found the ACC method to be a promising tool for the enrichment of Campylobacter species, particularly from water samples with low bacterial concentrations. PMID- 17873071 TI - Influence of native microbiota on survival of Ralstonia solanacearum phylotype II in river water microcosms. AB - Ralstonia solanacearum phylotype II biovar 2 causes bacterial wilt in solanaceous hosts, producing severe economic losses worldwide. Waterways can be major dissemination routes of this pathogen, which is able to survive for long periods in sterilized water. However, little is known about its survival in natural water when other microorganisms, such as bacteriophages, other bacteria, and protozoa, are present. This study looks into the fate of a Spanish strain of R. solanacearum inoculated in water microcosms from a Spanish river, containing different microbiota fractions, at 24 degrees C and 14 degrees C, for a month. At both temperatures, R. solanacearum densities remained constant at the initial levels in control microcosms of sterile river water while, by contrast, declines in the populations of the introduced strain were observed in the nonsterile microcosms. These decreases were less marked at 14 degrees C. Lytic bacteriophages present in this river water were involved in the declines of the pathogen populations, but indigenous protozoa and bacteria also contributed to the reduced persistence in water. R. solanacearum variants displaying resistance to phage infection were observed, but only in microcosms without protozoa and native bacteria. In water microcosms, the temperature of 14 degrees C was more favorable for the survival of this pathogen than 24 degrees C, since biotic interactions were slower at the lower temperature. Similar trends were observed in microcosms inoculated with a Dutch strain. This is the first study demonstrating the influence of different fractions of water microorganisms on the survival of R. solanacearum phylotype II released into river water microcosms. PMID- 17873070 TI - Evaluation of staphylococcal cell surface display and flow cytometry for postselectional characterization of affinity proteins in combinatorial protein engineering applications. AB - For efficient generation of high-affinity protein-based binding molecules, fast and reliable downstream characterization platforms are needed. In this work, we have explored the use of staphylococcal cell surface display together with flow cytometry for affinity characterization of candidate affibody molecules directly on the cell surface. A model system comprising three closely related affibody molecules with different affinities for immunoglobulin G and an albumin binding domain with affinity for human serum albumin was used to investigate advantages and differences compared to biosensor technology in a side-by-side manner. Equilibrium dissociation constant (K(D)) determinations as well as dissociation rate analysis were performed using both methods, and the results show that the on cell determinations give both K(D) and dissociation rate values in a very fast and reproducible manner and that the relative affinities are very similar to the biosensor results. Interestingly, the results also show that there are differences between the absolute affinities determined with the two different technologies, and possible explanations for this are discussed. This work demonstrates the advantages of cell surface display for directed evolution of affinity proteins in terms of fast postselectional, on-cell characterization of candidate clones without the need for subcloning and subsequent protein expression and purification but also demonstrates that it is important to be aware that absolute affinities determined using different methods often vary substantially and that such comparisons therefore could be difficult. PMID- 17873072 TI - Effects of plant biomass, plant diversity, and water content on bacterial communities in soil lysimeters: implications for the determinants of bacterial diversity. AB - Soils may comprise tens of thousands to millions of bacterial species. It is still unclear whether this high level of diversity is governed by functional redundancy or by a multitude of ecological niches. In order to address this question, we analyzed the reproducibility of bacterial community composition after different experimental manipulations. Soil lysimeters were planted with four different types of plant communities, and the water content was adjusted. Group-specific phylogenetic fingerprinting by PCR-denaturing gradient gel electrophoresis revealed clear differences in the composition of Alphaproteobacteria, Betaproteobacteria, Bacteroidetes, Chloroflexi, Planctomycetes, and Verrucomicrobia populations in soils without plants compared to that of populations in planted soils, whereas no influence of plant species composition on bacterial diversity could be discerned. These results indicate that the presence of higher plant species affects the species composition of bacterial groups in a reproducible manner and even outside of the rhizosphere. In contrast, the environmental factors tested did not affect the composition of Acidobacteria, Actinobacteria, Archaea, and Firmicutes populations. One-third (52 out of 160) of the sequence types were found to be specifically and reproducibly associated with the absence or presence of plants. Unexpectedly, this was also true for numerous minor constituents of the soil bacterial assemblage. Subsequently, one of the low-abundance phylotypes (beta10) was selected for studying the interdependence under particular experimental conditions and the underlying causes in more detail. This so-far-uncultured phylotype of the Betaproteobacteria species represented up to 0.18% of all bacterial cells in planted lysimeters compared to 0.017% in unplanted systems. A cultured representative of this phylotype exhibited high physiological flexibility and was capable of utilizing major constituents of root exudates. Our results suggest that the bacterial species composition in soil is determined to a significant extent by abiotic and biotic factors, rather than by mere chance, thereby reflecting a multitude of distinct ecological niches. PMID- 17873073 TI - Sensitive and specific molecular detection of Burkholderia pseudomallei, the causative agent of melioidosis, in the soil of tropical northern Australia. AB - Burkholderia pseudomallei, the cause of the severe disease melioidosis in humans and animals, is a gram-negative saprophyte living in soil and water of areas of endemicity such as tropical northern Australia and Southeast Asia. Infection occurs mainly by contact with wet contaminated soil. The environmental distribution of B. pseudomallei in northern Australia is still unclear. We developed and evaluated a direct soil B. pseudomallei DNA detection method based on the recently published real-time PCR targeting the B. pseudomallei type III secretion system. The method was evaluated by inoculating different soil types with B. pseudomallei dilution series and by comparing B. pseudomallei detection rate with culture-based detection rate for 104 randomly collected soil samples from the Darwin rural area in northern Australia. We found that direct soil B. pseudomallei DNA detection not only was substantially faster than culture but also proved to be more sensitive with no evident false-positive results. This assay provides a new tool to detect B. pseudomallei in soil samples in a fast and highly sensitive and specific manner and is applicable for large-scale B. pseudomallei environmental screening studies or in outbreak situations. Furthermore, analysis of the 104 collected soil samples revealed a significant association between B. pseudomallei-positive sites and the presence of animals at these locations and also with moist, reddish brown-to-reddish gray soils. PMID- 17873074 TI - An inducible propane monooxygenase is responsible for N-nitrosodimethylamine degradation by Rhodococcus sp. strain RHA1. AB - Rhodococci are common soil heterotrophs that possess diverse functional enzymatic activities with economic and ecological significance. In this study, the correlation between gene expression and biological removal of the water contaminant N-nitrosodimethylamine (NDMA) is explored. NDMA is a hydrophilic, potent carcinogen that has gained recent notoriety due to its environmental persistence and emergence as a widespread micropollutant in the subsurface environment. In this study, we demonstrate that Rhodococcus sp. strain RHA1 can constitutively degrade NDMA and that activity toward this compound is enhanced by approximately 500-fold after growth on propane. Transcriptomic analysis of RHA1 and reverse transcriptase quantitative PCR assays demonstrate that growth on propane elicits the upregulation of gene clusters associated with (i) the oxidation of propane and (ii) the oxidation of substituted benzenes. Deletion mutagenesis of prmA, the gene encoding the large hydroxylase component of propane monooxygenase, abolished both growth on propane and removal of NDMA. These results demonstrate that propane monooxygenase is responsible for NDMA degradation by RHA1 and explain the enhanced cometabolic degradation of NDMA in the presence of propane. PMID- 17873075 TI - Biodegradation of bis(2-chloroethyl) ether by Xanthobacter sp. strain ENV481. AB - Degradation of bis(2-chloroethyl) ether (BCEE) was observed to occur in two bacterial strains. Strain ENV481, a Xanthobacter sp. strain, was isolated by enrichment culturing of samples from a Superfund site located in the northeastern United States. The strain was able to grow on BCEE or 2-chloroethylethyl ether as the sole source of carbon and energy. BCEE degradation in strain ENV481 was facilitated by sequential dehalogenation reactions resulting in the formation of 2-(2-chloroethoxy)ethanol and diethylene glycol (DEG), respectively. 2 Hydroxyethoxyacetic acid was detected as a product of DEG catabolism by the strain. Degradation of BCEE by strain ENV481 was independent of oxygen, and the strain was not able to grow on a mixture of benzene, ethylbenzene, toluene, and xylenes, other prevalent contaminants at the site. Another bacterial isolate, Pseudonocardia sp. strain ENV478 (S. Vainberg et al., Appl. Environ. Microbiol. 72:5218-5224, 2006), degraded BCEE after growth on tetrahydrofuran or propane but was not able to grow on BCEE as a sole carbon source. BCEE degradation by strain ENV478 appeared to be facilitated by a monooxygenase-mediated O-dealkylation mechanism, and it resulted in the accumulation of 2-chloroacetic acid that was not readily degraded by the strain. PMID- 17873076 TI - Impact of zooplankton grazing on the excystation, viability, and infectivity of the protozoan pathogens Cryptosporidium parvum and Giardia lamblia. AB - Very little is known about the ability of the zooplankton grazer Daphnia pulicaria to reduce populations of Giardia lamblia cysts and Cryptosporidium parvum oocysts in surface waters. The potential for D. pulicaria to act as a biological filter of C. parvum and G. lamblia was tested under three grazing pressures (one, two, or four D. pulicaria grazers per 66 ml). (Oo)cysts (1 x 10(4) per 66 ml) were added to each grazing bottle along with the algal food Selenastrum capricornutum (6.6 x 10(4) cells per 66 ml) to stimulate normal grazing. Bottles were rotated (2 rpm) to prevent settling of (oo)cysts and algae for 24 h (a light:dark cycle of 16 h:8 h) at 20 degrees C. The impact of D. pulicaria grazing on (oo)cysts was assessed by (i) (oo)cyst clearance rates, (ii) (oo)cyst viability, (iii) (oo)cyst excystation, and (iv) oocyst infectivity in cell culture. Two D. pulicaria grazers significantly decreased the total number of C. parvum oocysts by 52% and G. lamblia cysts by 44%. Furthermore, two D. pulicaria grazers significantly decreased C. parvum excystation and infectivity by 5% and 87%, respectively. Two D. pulicaria grazers significantly decreased the viability of G. lamblia cysts by 52%, but analysis of G. lamblia excystation was confounded by observed mechanical disruption of the cysts after grazing. No mechanical disruption of the C. parvum oocysts was observed, presumably due to their smaller size. The data provide strong evidence that zooplankton grazers have the potential to substantially decrease the population of infectious C. parvum and G. lamblia in freshwater ecosystems. PMID- 17873077 TI - Heterologous production of dihomo-gamma-linolenic acid in Saccharomyces cerevisiae. AB - To make dihomo-gamma-linolenic acid (DGLA) (20:3n-6) in Saccharomyces cerevisiae, we introduced Kluyveromyces lactis Delta12 fatty acid desaturase, rat Delta6 fatty acid desaturase, and rat elongase genes. Because Fad2p is able to convert the endogenous oleic acid to linoleic acid, this allowed DGLA biosynthesis without the need to supply exogenous fatty acids on the media. Medium composition, cultivation temperature, and incubation time were examined to improve the yield of DGLA. Fatty acid content was increased by changing the medium from a standard synthetic dropout medium to a nitrogen-limited minimal medium (NSD). Production of DGLA was higher in the cells grown at 15 degrees C than in those grown at 20 degrees C, and no DGLA production was observed in the cells grown at 30 degrees C. In NSD at 15 degrees C, fatty acid content increased up until day 7 and decreased after day 10. When the cells were grown in NSD for 7 days at 15 degrees C, the yield of DGLA reached 2.19 microg/mg of cells (dry weight) and the composition of DGLA to total fatty acids was 2.74%. To our knowledge, this is the first report describing the production of polyunsaturated fatty acids in S. cerevisiae without supplying the exogenous fatty acids. PMID- 17873078 TI - Metabolic engineering of Lactobacillus plantarum for production of L-ribulose. AB - L-Ribulose is a rare and expensive sugar that can be used as a precursor for the production of other rare sugars of high market value such as L-ribose. In this work we describe a production process for L-ribulose using L-arabinose, a common component of polymers of lignocellulosic materials, as the starting material. A ribulokinase-deficient mutant of the heterofermentative lactic acid bacterium Lactobacillus plantarum NCIMB8826 was constructed. Expression of araA, which encodes the critical enzyme L-arabinose isomerase, was repressed by high glucose concentrations in batch cultivations. A fed-batch cultivation strategy was therefore used to maximize L-arabinose isomerase production during growth. Resting cells of the ribulokinase-deficient mutant were used for the production of L-ribulose. The isomerization of L-arabinose to L-ribulose was very unfavorable for L-ribulose formation. However, high L-ribulose yields were obtained by complexing the produced L-ribulose with borate. The process for L ribulose production in borate buffer by resting cells was optimized using central composite designs. The experiment design suggested that the process has an optimal operation point around an L-arabinose concentration of 100 g liter(-1), a borate concentration of 500 mM, and a temperature of 48 degrees C, where the statistical software predicted an initial L-ribulose production rate of 29.1 g liter(-1) h(-1), a best-achievable process productivity of 14.8 g liter(-1) h( 1), and a conversion of L-arabinose to L-ribulose of 0.70 mol mol(-1). PMID- 17873080 TI - The fungus-specific HET domain mediates programmed cell death in Podospora anserina. AB - Vegetative incompatibility is a programmed cell death reaction that occurs when fungal cells of unlike genotypes fuse. Genes defining vegetative incompatibility (het genes) are highly polymorphic, and most if not all incompatibility systems include a protein partner bearing the fungus-specific domain termed the HET domain. The nonallelic het-C/het-E incompatibility system is the best characterized incompatibility system in Podospora anserina. Cell death is triggered by interaction of specific alleles of het-C, encoding a glycolipid transfer protein, and het-E, encoding a HET domain and a WD repeat domain involved in recognition. We show here that overexpression of the isolated HET domain from het-E results in cell death. This cell death is characterized by induction of autophagy, increased vacuolization, septation, and production of lipid droplets, which are hallmarks of cell death by incompatibility. In addition, the HET domain lethality is suppressed by the same mutations as vegetative incompatibility, but not by the inactivation of het-C. These results establish the HET domain as the mediator of cell death by incompatibility and lead to a modular conception of incompatibility systems whereby recognition is ensured by the variable regions of incompatibility proteins and cell death is triggered by the HET domain. PMID- 17873079 TI - Supramolecular organization of the respiratory chain in Neurospora crassa mitochondria. AB - The existence of specific respiratory supercomplexes in mitochondria of most organisms has gained much momentum. However, its functional significance is still poorly understood. The availability of many deletion mutants in complex I (NADH:ubiquinone oxidoreductase) of Neurospora crassa, distinctly affected in the assembly process, offers unique opportunities to analyze the biogenesis of respiratory supercomplexes. Herein, we describe the role of complex I in assembly of respiratory complexes and supercomplexes as suggested by blue and colorless native polyacrylamide gel electrophoresis and mass spectrometry analyses of mildly solubilized mitochondria from the wild type and eight deletion mutants. As an important refinement of the fungal respirasome model, we found that the standard respiratory chain of N. crassa comprises putative complex I dimers in addition to I-III-IV and III-IV supercomplexes. Three Neurospora mutants able to assemble a complete complex I, lacking only the disrupted subunit, have respiratory supercomplexes, in particular I-III-IV supercomplexes and complex I dimers, like the wild-type strain. Furthermore, we were able to detect the I-III IV supercomplexes in the nuo51 mutant with no overall enzymatic activity, representing the first example of inactive respirasomes. In addition, III-IV supercomplexes were also present in strains lacking an assembled complex I, namely, in four membrane arm subunit mutants as well as in the peripheral arm nuo30.4 mutant. In membrane arm mutants, high-molecular-mass species of the 30.4 kDa peripheral arm subunit comigrating with III-IV supercomplexes and/or the prohibitin complex were detected. The data presented herein suggest that the biogenesis of complex I is linked with its assembly into supercomplexes. PMID- 17873081 TI - Requirement for Candida albicans Sun41 in biofilm formation and virulence. AB - The cell wall of Candida albicans lies at the crossroads of pathogenicity and therapeutics. It contributes to pathogenicity through adherence and invasion; it is the target of both chemical and immunological antifungal strategies. We have initiated a dissection of cell wall function through targeted insertional mutagenesis of cell wall-related genes. Among 25 such genes, we were unable to generate homozygous mutations in 4, and they may be essential for viability. We created homozygous mutations in the remaining 21 genes. Insertion mutations in SUN41, Orf19.5412, Orf19.1277, MSB2, Orf19.3869, and WSC1 caused hypersensitivity to the cell wall inhibitor caspofungin, while two different ecm33 insertions caused mild caspofungin resistance. Insertion mutations in SUN41 and Orf19.5412 caused biofilm defects. Through analysis of homozygous sun41Delta/sun41Delta deletion mutants and sun41Delta/sun41Delta+pSUN41-complemented strains, we verified that Sun41 is required for biofilm formation and normal caspofungin tolerance. The sun41Delta/sun41Delta mutant had altered expression of four cell wall damage response genes, thus suggesting that it suffers a cell wall structural defect. Sun41 is required for inducing disease, because the mutant was severely attenuated in mouse models of disseminated and oropharyngeal candidiasis. Although the mutant produced aberrant hyphae, it had no defect in damaging endothelial or epithelial cells, unlike many other hypha-defective mutants. We suggest that the sun41Delta/sun41Delta cell wall defect is the primary cause of its attenuated virulence. As a small fungal surface protein with predicted glucosidase activity, Sun41 represents a promising therapeutic target. PMID- 17873082 TI - A chemogenomic screening of sulfanilamide-hypersensitive Saccharomyces cerevisiae mutants uncovers ABZ2, the gene encoding a fungal aminodeoxychorismate lyase. AB - Large-scale phenotypic analyses have proved to be useful strategies in providing functional clues about the uncharacterized yeast genes. We used here a chemogenomic profiling of yeast deletion collections to identify the core of cellular processes challenged by treatment with the p-aminobenzoate/folate antimetabolite sulfanilamide. In addition to sulfanilamide-hypersensitive mutants whose deleted genes can be categorized into a number of groups, including one carbon related metabolism, vacuole biogenesis and vesicular transport, DNA metabolic and cell cycle processes, and lipid and amino acid metabolism, two uncharacterized open reading frames (YHI9 and YMR289w) were also identified. A detailed characterization of YMR289w revealed that this gene was required for growth in media lacking p-aminobenzoic or folic acid and encoded a 4-amino-4 deoxychorismate lyase, which is the last of the three enzymatic activities required for p-aminobenzoic acid biosynthesis. In light of these results, YMR289w was designated ABZ2, in accordance with the accepted nomenclature. ABZ2 was able to rescue the p-aminobenzoate auxotrophy of an Escherichia coli pabC mutant, thus demonstrating that ABZ2 and pabC are functional homologues. Phylogenetic analyses revealed that Abz2p is the founder member of a new group of fungal 4-amino-4 deoxychorismate lyases that have no significant homology to its bacterial or plant counterparts. Abz2p appeared to form homodimers and dimerization was indispensable for its catalytic activity. PMID- 17873083 TI - Novel membrane-bound eIF2alpha kinase in the flagellar pocket of Trypanosoma brucei. AB - Translational control mediated by phosphorylation of the alpha subunit of the eukaryotic initiation factor 2 (eIF2alpha) is central to stress-induced programs of gene expression. Trypanosomatids, important human pathogens, display differentiation processes elicited by contact with the distinct physiological milieu found in their insect vectors and mammalian hosts, likely representing stress situations. Trypanosoma brucei, the agent of African trypanosomiasis, encodes three potential eIF2alpha kinases (TbeIF2K1 to -K3). We show here that TbeIF2K2 is a transmembrane glycoprotein expressed both in procyclic and in bloodstream forms. The catalytic domain of TbeIF2K2 phosphorylates yeast and mammalian eIF2alpha at Ser51. It also phosphorylates the highly unusual form of eIF2alpha found in trypanosomatids specifically at residue Thr169 that corresponds to Ser51 in other eukaryotes. T. brucei eIF2alpha, however, is not a substrate for GCN2 or PKR in vitro. The putative regulatory domain of TbeIF2K2 does not share any sequence similarity with known eIF2alpha kinases. In both procyclic and bloodstream forms TbeIF2K2 is mainly localized in the membrane of the flagellar pocket, an organelle that is the exclusive site of exo- and endocytosis in these parasites. It can also be detected in endocytic compartments but not in lysosomes, suggesting that it is recycled between endosomes and the flagellar pocket. TbeIF2K2 location suggests a relevance in sensing protein or nutrient transport in T. brucei, an organism that relies heavily on posttranscriptional regulatory mechanisms to control gene expression in different environmental conditions. This is the first membrane-associated eIF2alpha kinase described in unicellular eukaryotes. PMID- 17873084 TI - Small trypanosome RNA-binding proteins TbUBP1 and TbUBP2 influence expression of F-box protein mRNAs in bloodstream trypanosomes. AB - In the African trypanosome Trypanosoma brucei nearly all control of gene expression is posttranscriptional; sequences in the 3'-untranslated regions of mRNAs determine the steady-state mRNA levels by regulation of RNA turnover. Here we investigate the roles of two related proteins, TbUBP1 and TbUBP2, containing a single RNA recognition motif, in trypanosome gene expression. TbUBP1 and TbUBP2 are in the cytoplasm and nucleus, comprise ca. 0.1% of the total protein, and are not associated with polysomes or RNA degradation enzymes. Overexpression of TbUBP2 upregulated the levels of several mRNAs potentially involved in cell division, including the CFB1 mRNA, which encodes a protein with a cyclin F-box domain. CFB1 regulation was mediated by the 3'-untranslated region and involved stabilization of the mRNA. Depletion of TbUBP2 and TbUBP1 inhibited growth and downregulated expression of the cyclin F box protein gene CFB2; trans splicing was unaffected. The results of pull-down assays indicated that all tested mRNAs were bound to TbUBP2 or TbUBP1, with some preference for CFB1. We suggest that TbUBP1 and TbUBP2 may be relatively nonspecific RNA-binding proteins and that specific effects of overexpression or depletion could depend on competition between various different proteins for RNA binding. PMID- 17873085 TI - Multidrug resistance in fungi. PMID- 17873086 TI - Expression of hygromycin phosphotransferase alters virulence of Histoplasma capsulatum. AB - The Escherichia coli hygromycin phosphotransferase (hph) gene, which confers hygromycin resistance, is commonly used as a dominant selectable marker in genetically modified bacteria, fungi, plants, insects, and mammalian cells. Expression of the hph gene has rarely been reported to induce effects other than those expected. Hygromycin B is the most common dominant selectable marker used in the molecular manipulation of Histoplasma capsulatum in the generation of knockout strains of H. capsulatum or as a marker in mutant strains. hph expressing organisms appear to have no defect in long-term in vitro growth and survival and have been successfully used to exploit host-parasite interaction in short-term cell culture systems and animal experiments. We introduced the hph gene as a selectable marker together with the gene encoding green fluorescent protein into wild-type strains of H. capsulatum. Infection of mice with hph expressing H. capsulatum yeast cells at sublethal doses resulted in lethality. The lethality was not attributable to the site of integration of the hph construct into the genomes or to the method of integration and was not H. capsulatum strain related. Death of mice was not caused by altered cytokine profiles or an overwhelming fungal burden. The lethality was dependent on the kinase activity of hygromycin phosphotransferase. These results should raise awareness of the potential detrimental effects of the hph gene. PMID- 17873087 TI - Dual role of the plastid terminal oxidase in tomato. AB - The plastid terminal oxidase (PTOX) is a plastoquinol oxidase whose absence in tomato (Solanum lycopersicum) results in the ghost (gh) phenotype characterized by variegated leaves (with green and bleached sectors) and by carotenoid deficient ripe fruit. We show that PTOX deficiency leads to photobleaching in cotyledons exposed to high light primarily as a consequence of reduced ability to synthesize carotenoids in the gh mutant, which is consistent with the known role of PTOX as a phytoene desaturase cofactor. In contrast, when entirely green adult leaves from gh were produced and submitted to photobleaching high light conditions, no evidence for a deficiency in carotenoid biosynthesis was obtained. Rather, consistent evidence indicates that the absence of PTOX renders the tomato leaf photosynthetic apparatus more sensitive to light via a disturbance of the plastoquinone redox status. Although gh fruit are normally bleached (most likely as a consequence of a deficiency in carotenoid biosynthesis at an early developmental stage), green adult fruit could be obtained and submitted to photobleaching high light conditions. Again, our data suggest a role of PTOX in the regulation of photosynthetic electron transport in adult green fruit, rather than a role principally devoted to carotenoid biosynthesis. In contrast, ripening fruit are primarily dependent on PTOX and on plastid integrity for carotenoid desaturation. In summary, our data show a dual role for PTOX. Its activity is necessary for efficient carotenoid desaturation in some organs at some developmental stages, but not all, suggesting the existence of a PTOX-independent pathway for plastoquinol reoxidation in association with phytoene desaturase. As a second role, PTOX is implicated in a chlororespiratory mechanism in green tissues. PMID- 17873088 TI - Vitamer levels, stress response, enzyme activity, and gene regulation of Arabidopsis lines mutant in the pyridoxine/pyridoxamine 5'-phosphate oxidase (PDX3) and the pyridoxal kinase (SOS4) genes involved in the vitamin B6 salvage pathway. AB - PDX3 and SALT OVERLY SENSITIVE4 (SOS4), encoding pyridoxine/pyridoxamine 5' phosphate oxidase and pyridoxal kinase, respectively, are the only known genes involved in the salvage pathway of pyridoxal 5'-phosphate in plants. In this study, we determined the phenotype, stress responses, vitamer levels, and regulation of the vitamin B(6) pathway genes in Arabidopsis (Arabidopsis thaliana) plants mutant in PDX3 and SOS4. sos4 mutant plants showed a distinct phenotype characterized by chlorosis and reduced plant size, as well as hypersensitivity to sucrose in addition to the previously noted NaCl sensitivity. This mutant had higher levels of pyridoxine, pyridoxamine, and pyridoxal 5' phosphate than the wild type, reflected in an increase in total vitamin B(6) observed through HPLC analysis and yeast bioassay. The sos4 mutant showed increased activity of PDX3 as well as of the B(6) de novo pathway enzyme PDX1, correlating with increased total B(6) levels. Two independent lines with T-DNA insertions in the promoter region of PDX3 (pdx3-1 and pdx3-2) had decreased PDX3 activity. Both also had decreased activity of PDX1, which correlated with lower levels of total vitamin B(6) observed using the yeast bioassay; however, no differences were noted in levels of individual vitamers by HPLC analysis. Both pdx3 mutants showed growth reduction in vitro and in vivo as well as an inability to increase growth under high light conditions. Increased expression of salvage and some of the de novo pathway genes was observed in both the pdx3 and sos4 mutants. In all mutants, increased expression was more dramatic for the salvage pathway genes. PMID- 17873089 TI - Unraveling the difference between invertases and fructan exohydrolases: a single amino acid (Asp-239) substitution transforms Arabidopsis cell wall invertase1 into a fructan 1-exohydrolase. AB - Plant cell wall invertases and fructan exohydrolases (FEHs) are very closely related enzymes at the molecular and structural level (family 32 of glycoside hydrolases), but they are functionally different and are believed to fulfill distinct roles in plants. Invertases preferentially hydrolyze the glucose (Glc) fructose (Fru) linkage in sucrose (Suc), whereas plant FEHs have no invertase activity and only split terminal Fru-Fru linkages in fructans. Recently, the three-dimensional structures of Arabidopsis (Arabidopsis thaliana) cell wall Invertase1 (AtcwINV1) and chicory (Cichorium intybus) 1-FEH IIa were resolved. Until now, it remained unknown which amino acid residues determine whether Suc or fructan is used as a donor substrate in the hydrolysis reaction of the glycosidic bond. In this article, we present site-directed mutagenesis-based data on AtcwINV1 showing that the aspartate (Asp)-239 residue fulfills an important role in both binding and hydrolysis of Suc. Moreover, it was found that the presence of a hydrophobic zone at the rim of the active site is important for optimal and stable binding of Suc. Surprisingly, a D239A mutant acted as a 1-FEH, preferentially degrading 1-kestose, indicating that plant FEHs lacking invertase activity could have evolved from a cell wall invertase-type ancestor by a few mutational changes. In general, family 32 and 68 enzymes containing an Asp-239 functional homolog have Suc as a preferential substrate, whereas enzymes lacking this homolog use fructans as a donor substrate. The presence or absence of such an Asp-239 homolog is proposed as a reliable determinant to discriminate between real invertases and defective invertases/FEHs. PMID- 17873090 TI - Transcription factor RAP2.2 and its interacting partner SINAT2: stable elements in the carotenogenesis of Arabidopsis leaves. AB - The promoter of phytoene synthase, the first specific enzyme of carotenoid biosynthesis, shows two main regulatory regions: a G-box-containing region located near the TATA box, and a TATA box distal region containing the cis-acting element ATCTA, which mediates strong basal promoter activity. This second element was also present in the promoter of phytoene desaturase, the next step of the carotenoid pathway, suggesting a common regulatory mechanism. In this work, we demonstrate that AtRAP2.2, a member of the APETALA2 (AP2)/ethylene-responsive element-binding protein transcription factor family, binds to the ATCTA element. In Arabidopsis (Arabidopsis thaliana) leaves, AtRAP2.2 transcript and protein levels were tightly controlled as indicated by unchanged transcript and protein levels in T-DNA insertion mutants in the AtRAP2.2 promoter and 5' untranslated region and the lack of change in AtRAP2.2 protein levels in lines strongly overexpressing the AtRAP2.2 transcript. Homozygous loss-of-function mutants could not be obtained for the AtRAP2.2 5' untranslated region T-DNA insertion line indicating a lethal phenotype. In AtRAP2.2 overexpression lines, modest changes in phytoene synthase and phytoene desaturase transcripts were only observed in root-derived calli, which consequently showed a reduction in carotenoid content. The RING finger protein SEVEN IN ABSENTIA OF ARABIDOPSIS2 (SINAT2) was identified as an AtRAP2.2 interaction partner using a two-hybrid approach. The structure of SINAT2 and related proteins of Arabidopsis show homology to the SEVEN IN ABSENTIA protein of Drosophila that is involved in proteasome-mediated regulation in a variety of developmental processes. The action of SINAT2 may explain the recalcitrance of AtRAP2.2 protein levels to change by altering AtRAP2.2 transcription. PMID- 17873091 TI - CIRCADIAN CLOCK ASSOCIATED1 transcript stability and the entrainment of the circadian clock in Arabidopsis. AB - The circadian clock is an endogenous mechanism that generates rhythms with an approximately 24-h period and enables plants to predict and adapt to daily and seasonal changes in their environment. These rhythms are generated by molecular oscillators that in Arabidopsis (Arabidopsis thaliana) have been shown to consist of interlocking feedback loops involving a number of elements. An important characteristic of circadian oscillators is that they can be entrained by daily environmental changes in light and temperature. Previous work has shown that one possible entrainment point for the Arabidopsis oscillator is the light-mediated regulation of expression of one of the oscillator genes, CIRCADIAN CLOCK ASSOCIATED1 (CCA1). In this article, we have used transgenic plants with constitutive CCA1 expression to show that light also regulates CCA1 transcript stability. Our experiments show that CCA1 messenger RNA is relatively stable in the dark and in far-red light but has a short half-life in red and blue light. Furthermore, using transgenic plants expressing chimeric CCA1 constructs, we demonstrate that the instability determinants in CCA1 transcripts are probably located in the coding region. We suggest that the combination of light regulation of CCA1 transcription and CCA1 messenger RNA degradation is important for ensuring that the Arabidopsis circadian oscillator is accurately entrained by environmental changes. PMID- 17873093 TI - The Arabidopsis CLASP gene encodes a microtubule-associated protein involved in cell expansion and division. AB - Controlling microtubule dynamics and spatial organization is a fundamental requirement of eukaryotic cell function. Members of the ORBIT/MAST/CLASP family of microtubule-associated proteins associate with the plus ends of microtubules, where they promote the addition of tubulin subunits into attached kinetochore fibers during mitosis and stabilize microtubules in the vicinity of the plasma membrane during interphase. To date, nothing is known about their function in plants. Here, we show that the Arabidopsis thaliana CLASP protein is a microtubule-associated protein that is involved in both cell division and cell expansion. Green fluorescent protein-CLASP localizes along the full length of microtubules and shows enrichment at growing plus ends. Our analysis suggests that CLASP promotes microtubule stability. clasp-1 T-DNA insertion mutants are hypersensitive to microtubule-destabilizing drugs and exhibit more sparsely populated, yet well ordered, root cortical microtubule arrays. Overexpression of CLASP promotes microtubule bundles that are resistant to depolymerization with oryzalin. Furthermore, clasp-1 mutants have aberrant microtubule preprophase bands, mitotic spindles, and phragmoplasts, indicating a role for At CLASP in stabilizing mitotic arrays. clasp-1 plants are dwarf, have significantly reduced cell numbers in the root division zone, and have defects in directional cell expansion. We discuss possible mechanisms of CLASP function in higher plants. PMID- 17873092 TI - INCURVATA2 encodes the catalytic subunit of DNA Polymerase alpha and interacts with genes involved in chromatin-mediated cellular memory in Arabidopsis thaliana. AB - Cell type-specific gene expression patterns are maintained by the stable inheritance of transcriptional states through mitosis, requiring the action of multiprotein complexes that remodel chromatin structure. Genetic and molecular interactions between chromatin remodeling factors and components of the DNA replication machinery have been identified in Schizosaccharomyces pombe, indicating that some epigenetic marks are replicated simultaneously to DNA with the participation of the DNA replication complexes. This model of epigenetic inheritance might be extended to the plant kingdom, as we report here with the positional cloning and characterization of INCURVATA2 (ICU2), which encodes the putative catalytic subunit of the DNA polymerase alpha of Arabidopsis thaliana. The strong icu2-2 and icu2-3 insertional alleles caused fully penetrant zygotic lethality when homozygous and incompletely penetrant gametophytic lethality, probably because of loss of DNA polymerase activity. The weak icu2-1 allele carried a point mutation and caused early flowering, leaf incurvature, and homeotic transformations of sepals into carpels and of petals into stamens. Further genetic analyses indicated that ICU2 interacts with TERMINAL FLOWER2, the ortholog of HETEROCHROMATIN PROTEIN1 of animals and yeasts, and with the Polycomb group (PcG) gene CURLY LEAF. Another PcG gene, EMBRYONIC FLOWER2, was found to be epistatic to ICU2. Quantitative RT-PCR analyses indicated that a number of regulatory genes were derepressed in the icu2-1 mutant, including genes associated with flowering time, floral meristem, and floral organ identity. PMID- 17873094 TI - Nucleocytoplasmic shuttling of BZR1 mediated by phosphorylation is essential in Arabidopsis brassinosteroid signaling. AB - Phytohormone brassinosteroids (BRs) play critical roles in plant growth and development. BR acts by modulating the phosphorylation status of two key transcriptional factors, BRI1 EMS SUPPRESSOR1 and BRASSINAZOLE RESISTANT1 (BZR1), through the action of BRASSINOSTEROID INSENSITIVE1/BRI1 ASSOCIATED RECEPTOR KINASE1 receptors and a GSK3 kinase, BRASSINOSTEROID INSENSITIVE2 (BIN2). It is still unknown how the perception of BR at the plasma membrane connects to the expression of BR target genes in the nucleus. We show here that BZR1 functions as a nucleocytoplasmic shuttling protein and GSK3-like kinases induce the nuclear export of BZR1 by modulating BZR1 interaction with the 14-3-3 proteins. BR activated phosphatase mediates rapid nuclear localization of BZR1. Besides the phosphorylation domain for 14-3-3 binding, another phosphorylation domain in BZR1 is required for the BIN2-induced nuclear export of BZR1. Mutations of putative phosphorylation sites in two distinct domains enhance the nuclear retention of BZR1 and BR responses in transgenic plants. We propose that the spatial redistribution of BZR1 is critical for proper BR signaling in plant growth and development. PMID- 17873096 TI - LITTLE NUCLEI genes affecting nuclear morphology in Arabidopsis thaliana. AB - Efforts to understand nuclear organization in plant cells have received little assistance from the better-studied animal nuclei, because plant proteomes do not contain recognizable counterparts to the key animal proteins involved in nuclear organization, such as lamin nuclear intermediate filament proteins. Previous studies identified a plant-specific insoluble nuclear protein in carrot (Daucus carota), called Nuclear Matrix Constituent Protein1 (NMCP1), which contains extensive coiled-coil domains and localizes to the nuclear periphery. Here, we describe a genetic characterization of two NMCP1-related nuclear proteins in Arabidopsis thaliana, LITTLE NUCLEI1 (LINC1) and LINC2. Disruption of either gene caused a reduction in nuclear size and altered nuclear morphology. Moreover, combining linc1 and linc2 mutations had an additive effect on nuclear size and morphology but a synergistic effect on chromocenter number (reduction) and whole plant morphology (dwarfing). The reduction in nuclear size in the linc1 linc2 double mutant was not accompanied by a corresponding change in endopolyploidy. Rather, the density of DNA packaging at all endopolyploid levels in the linc1 linc2 mutants was increased significantly. Our results indicate that the LINC coiled-coil proteins are important determinants of plant nuclear structure. PMID- 17873095 TI - Crystal structures of flax rust avirulence proteins AvrL567-A and -D reveal details of the structural basis for flax disease resistance specificity. AB - The gene-for-gene mechanism of plant disease resistance involves direct or indirect recognition of pathogen avirulence (Avr) proteins by plant resistance (R) proteins. Flax rust (Melampsora lini) AvrL567 avirulence proteins and the corresponding flax (Linum usitatissimum) L5, L6, and L7 resistance proteins interact directly. We determined the three-dimensional structures of two members of the AvrL567 family, AvrL567-A and AvrL567-D, at 1.4- and 2.3-A resolution, respectively. The structures of both proteins are very similar and reveal a beta sandwich fold with no close known structural homologs. The polymorphic residues in the AvrL567 family map to the surface of the protein, and polymorphisms in residues associated with recognition differences for the R proteins lead to significant changes in surface chemical properties. Analysis of single amino acid substitutions in AvrL567 proteins confirm the role of individual residues in conferring differences in recognition and suggest that the specificity results from the cumulative effects of multiple amino acid contacts. The structures also provide insights into possible pathogen-associated functions of AvrL567 proteins, with nucleic acid binding activity demonstrated in vitro. Our studies provide some of the first structural information on avirulence proteins that bind directly to the corresponding resistance proteins, allowing an examination of the molecular basis of the interaction with the resistance proteins as a step toward designing new resistance specificities. PMID- 17873097 TI - Returning to our roots: making plant biology research relevant to future challenges in agriculture. PMID- 17873099 TI - Socioeconomic gradients in immune response to latent infection. AB - There is a strong relation between socioeconomic position and health outcomes, although the mechanisms are poorly understood. The authors used data from 1,503 California participants in the 1998-1999 Sacramento Area Latino Study on Aging aged 60-100 years to ask whether socioeconomic position is related to immune function as measured by the body's ability to keep latent herpesvirus antibody levels in a quiescent state. Individuals with lower educational levels had significantly higher levels of immunoglobulin G antibodies to cytomegalovirus and herpes simplex virus type 1. The odds ratio for being in a higher tertile of cytomegalovirus antibodies was 1.54 (95% confidence interval: 1.18, 2.01) for those in the lowest educational group, and the odds ratio for being in a higher tertile of herpes simplex virus type 1 was 1.63 (95% confidence interval: 1.25, 2.13). The relation between education and cytomegalovirus and herpes simplex virus type 1 antibody levels remained strong after controlling for baseline health conditions, smoking status, and body mass index. This is the first study known to show a relation between socioeconomic position and immune response to latent infection. It provides suggestive evidence that modulation of the immune system via latent infections may play a role in the observed associations between socioeconomic position and disease. PMID- 17873098 TI - The Arabidopsis BEL1-LIKE HOMEODOMAIN proteins SAW1 and SAW2 act redundantly to regulate KNOX expression spatially in leaf margins. AB - In Arabidopsis thaliana, the BEL1-like TALE homeodomain protein family consists of 13 members that form heterodimeric complexes with the Class 1 KNOX TALE homeodomain proteins, including SHOOTMERISTEMLESS (STM) and BREVIPEDICELLUS (BP). The BEL1-like protein BELLRINGER (BLR) functions together with STM and BP in the shoot apex to regulate meristem identity and function and to promote correct shoot architecture. We have characterized two additional BEL1-LIKE HOMEODOMAIN (BLH) proteins, SAWTOOTH1 (BLH2/SAW1) and SAWTOOTH2 (BLH4/SAW2) that, in contrast with BLR, are expressed in lateral organs and negatively regulate BP expression. saw1 and saw2 single mutants have no obvious phenotype, but the saw1 saw2 double mutant has increased leaf serrations and revolute margins, indicating that SAW1 and SAW2 act redundantly to limit leaf margin growth. Consistent with this hypothesis, overexpression of SAW1 suppresses overall growth of the plant shoot. BP is ectopically expressed in the leaf serrations of saw1 saw2 double mutants. Ectopic expression of Class 1 KNOX genes in leaves has been observed previously in loss-of-function mutants of ASYMMETRIC LEAVES (AS1). Overexpression of SAW1 in an as1 mutant suppresses the as1 leaf phenotype and reduces ectopic BP leaf expression. Taken together, our data suggest that BLH2/SAW1 and BLH4/SAW2 establish leaf shape by repressing growth in specific subdomains of the leaf at least in part by repressing expression of one or more of the KNOX genes. PMID- 17873100 TI - Transport cycle intermediate in small multidrug resistance protein is revealed by substrate fluorescence. AB - Efflux pumps of the small multidrug resistance family bind cationic, lipophilic antibiotics and transport them across the membrane in exchange for protons. The transport cycle must involve various conformational states of the protein needed for substrate binding, translocation, and release. A fluorescent substrate will therefore experience a significant change of environment while being transported, which influences its fluorescence properties. Thus the substrate itself can report intermediate states that form during the transport cycle. We show the existence of such a substrate-transporter complex for the EmrE homolog Mycobacterium tuberculosis TBsmr and its substrate ethidium bromide. The pH gradient needed for antiport has been generated by co-reconstituting TBsmr with bacteriorhodopsin. Sample illumination generates a DeltapH, which results in enhanced ethidium fluorescence intensity, which is abolished when DeltapH or DeltaPsi is collapsed or when the essential residue Glu-13 in TBsmr is exchanged with Ala. This observation shows the formation of a pH-dependent, transient substrate-protein complex between binding and release of ethidium. We have further characterized this state by determining the K(d), by inhibiting ethidium transport through titration with nonfluorescent substrate and by fluorescence anisotropy measurements. Our findings support a model with a single occluded intermediate state in which the substrate is highly immobile. PMID- 17873101 TI - Dendritic cells support angiogenesis and promote lesion growth in a murine model of endometriosis. AB - Endometriosis affects 10-15% of women and is associated with pelvic pain and infertility. Angiogenesis plays an essential role in its pathogenesis. Dendritic cells (DCs) were recently implicated in supporting tumor angiogenesis. As both tumors and endometriosis lesions depend on angiogenesis, we investigated the possibility that DCs may also play a role in endometriosis. We induced endometriosis in 8-wk-old female C57BL/6 mice by implantation of autologous endometrium into the peritoneal cavity. We observed an abundance of CD11c(+) DCs infiltrating sites of angiogenesis in endometriosis lesions. We noticed a similar pattern of infiltrating DCs at sites of angiogenesis in the peritoneal Lewis lung carcinoma tumor model. These DCs were immature (major histocompatability complex class II(low)) and expressed vascular endothelial growth factor receptor 2. Peritoneal implanted bone marrow-derived DCs (BMDCs) incorporated into both endometriosis lesions and into B16 melanoma tumors and enhanced their growth at 8 days compared with controls (5.1+/-2.5 vs. 1.5+/-0.5 mm(2), n=4 and 4, P<0.0001 for endometriosis; 67.6+/-15.1 vs. 22.7+/-14.6 mm(2), n=5 and 7, P=0.0004 for mouse melanoma). Finally, immature BMDCs but not mature BMDCs enhanced microvascular endothelial cell migration in vitro (219+/-51 vs. 93+/-32 cells, P=0.02). Based on these findings, we suggest a novel role for DCs in supporting angiogenesis and promoting lesion growth both in endometriosis and in tumors. PMID- 17873102 TI - Adeno-associated virus (AAV)-mediated transduction of male germ line stem cells results in transgene transmission after germ cell transplantation. AB - We explored whether exposure of mammalian germ line stem cells to adeno associated virus (AAV), a gene therapy vector, would lead to stable transduction and transgene transmission. Mouse germ cells harvested from experimentally induced cryptorchid donor testes were exposed in vitro to AAV vectors carrying a GFP transgene and transplanted to germ cell-depleted syngeneic recipient testes, resulting in colonization of the recipient testes by transgenic donor cells. Mating of recipient males to wild-type females yielded 10% transgenic offspring. To broaden the approach to nonrodent species, AAV-transduced germ cells from goats were transplanted to recipient males in which endogenous germ cells had been depleted by fractionated testicular irradiation. Transgenic germ cells colonized recipient testes and produced transgenic sperm. When semen was used for in vitro fertilization (IVF), 10% of embryos were transgenic. Here, we report for the first time that AAV-mediated transduction of mammalian germ cells leads to transmission of the transgene through the male germ line. Equally important, this is also the first report of transgenesis via germ cell transplantation in a nonrodent species, a promising approach to generate transgenic large animal models for biomedical research. PMID- 17873103 TI - In vivo fate and therapeutic efficacy of PF-4/CTF microspheres in an orthotopic human glioblastoma model. AB - The correlation between glioma grade and angiogenesis suggests that antiangiogenic therapies are potentially therapeutically effective for these tumors. However, to achieve tumor suppression, antiangiogenic therapies need to be administered daily using high systemic quantities. We designed a biodegradable polymeric device that overcomes those barriers by providing sustained local delivery of a C-terminal fragment of platelet factor 4 (PF-4/CTF), an antiangiogenic agent. Fluorescent-labeled microspheres composed of poly lactic coglycolic acid (PLGA) were loaded with rhodamine-labeled PF-4/CTF and formulated to release their contents over time. Fluorescent labeling enabled the correlation between the in vitro to the in vivo kinetic and release studies. PF-4/CTF microspheres were injected into established intracranial human glioma tumors in nude mice. Noninvasive magnetic resonance imaging (MRI) was used to assess the therapeutic response. Tumor size, microvessel density, proliferation, and apoptosis rate were measured by histological analysis. Intracranially, the microspheres were located throughout the tumor bed and continuously released PF 4/CTF during the entire experimental period. MRI and histological studies showed that a single injection of microspheres containing PF-4/CTF caused a 65.2% and 72% reduction in tumor volume, respectively, with a significant decrease in angiogenesis and an increase in apoptosis. Our data demonstrate that polymeric microspheres are an effective therapeutic approach for delivering antiangiogenic agents that result in the inhibition of glioma tumor growth. PMID- 17873104 TI - Cardioprotection by sulfaphenazole, a cytochrome p450 inhibitor: mitigation of ischemia-reperfusion injury by scavenging of reactive oxygen species. AB - Cytochrome P450 (P450) enzymes play a significant role in promoting myocardial ischemia-reperfusion (I/R) injury. CYP2C9, an isoform of P450, is known to generate superoxide radicals in the reperfused heart. Sulfaphenazole (SPZ), a CYP2C9 inhibitor, has been shown to decrease I/R injury; however, the mechanism of cardioprotection by SPZ is not well elucidated. The objective of this study was to test whether SPZ mitigates myocardial I/R injury by scavenging reactive oxygen species (ROS). Isolated rat hearts were subjected to 30 min of global ischemia followed by 45 min of reperfusion. Hearts were perfused with SPZ and/or N(omega)-nitro-L-arginine methylester (L-NAME). Coronary flow (CF), left ventricular developed pressure (LVDP), and rate-pressure product (RPP) were monitored. Superoxide and nitric oxide (NO) generation in the reperfused tissue was determined using fluorescence methods. Myocardial infarct size was measured using triphenyltetrazolium chloride staining. The SPZ-treated group showed a significant recovery of cardiac function compared with the untreated I/R group (CF, 53 versus 45%; LVDP, 48 versus 22%; RPP, 51 versus 20%). The infarct size was significantly reduced in the SPZ-treated group (15%) compared with the I/R control (42%). Coadministration of L-NAME with SPZ significantly attenuated the beneficial effects of SPZ. In addition, SPZ treatment showed significantly decreased superoxide levels and enhanced NO bioavailability in the reperfused heart. In conclusion, the protective effect of SPZ against I/R-mediated myocardial damage appears to be due to a reduction in the superoxide level caused by its inhibition of CYP2C9, as well as scavenging of oxygen free radicals generated in the reperfused heart. PMID- 17873105 TI - Negative allosteric modulation of nicotinic acetylcholine receptors blocks nicotine self-administration in rats. AB - Drugs that antagonize nicotinic acetylcholine receptors (nAChRs) can be used to inhibit nicotine-induced behavior in both humans and animals. The aim of our experiments is to establish a proof-of-principle that antagonism of nAChRs by negative allosteric modulation can alter behavior in a relevant animal model of addiction, nicotine self-administration. We have identified a novel, negative allosteric modulator of nAChRs, UCI-30002 [N-(1,2,3,4-tetrahydro-1-naphthyl)-4 nitroaniline], with selectivity for the major neuronal nAChR subtypes over muscle type nAChRs. After systemic administration, UCI-30002 significantly reduces nicotine self-administration in rats on both fixed ratio and progressive ratio schedules of reinforcement. The minimum effective dose that significantly alters nicotine self-administration corresponds to brain concentrations of UCI-30002 that produce at least 30% inhibition of the major neuronal nAChR subtypes measured in vitro. UCI-30002 has no effect on responding for food reinforcement in rats on either type of schedule, indicating that there is no effect on general responding or natural reward. UCI-30002 represents validation of the concept that negative allosteric modulators may have significant benefits as a strategy for treating nicotine addiction and encourages the development of subtype-selective modulators. PMID- 17873107 TI - Evaluation of the design and reliability of three elastomeric and one mechanical infusers. AB - BACKGROUND: Disposable elastomeric and mechanical (spring mechanism) infusers with pre-fixed flow rates are principally used for long-term antibiotic therapy, chemotherapy, antiviral therapy, and chronic pain management. METHODS: Three elastomeric pumps and one mechanical infuser pump are evaluated. The design and function are assessed using specific questionnaires elaborated for the pharmaceutical staff, nurses and patients, respectively. Several tests are performed to determine the flow accuracy and the influence of different parameters such as the temperature, the viscosity, the height, and the restrictor variability. RESULTS: The functional tests show that the perfusion duration is shorter than that specified by the manufacturers, the restrictors are not homogeneous within a batch. However, the temperature of the regulator, the viscosity of the solution, and the height of the reservoir influence the flow rate. CONCLUSIONS: The ideal infuser should be small, light, unnoticeable, easy to fill, well identified and have a flow rate barely affected by external factors. None of the infusers has fulfilled all criteria, therefore the choice of infusers depends upon the nature of the treatment. The tested elastomeric infusers are adequate for 5-fluorouracil, but not for a treatment requiring a stable administration rate. PMID- 17873106 TI - Management of platinum-based chemotherapy-induced acute nausea and vomiting: is there a superior serotonin receptor antagonist? AB - OBJECTIVE: The last decade has witnessed the great impact of 5-hydroxytryptamine 3 receptor (5-HT(3))antagonists in revolutionizing the management of platinum based chemotherapy-induced acute nausea and vomiting (CINV). However, despite the availability of a variety of 5-HT(3) antagonists, little data is published to support superiority of one drug over another, leaving the choice of serotonin receptor antagonist largely empirical. The National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines for management of chemotherapy-associated nausea and vomiting cleary endorse the use of serotonin receptor antagonist; however, no single agent is preferred over the rest. METHODS: Data for patients (n=159) receiving platinum-based chemotherapy regimens were retrospectively collected . Patients getting 5-HT(3) antagonists without steriods or those with known history of brain metastasis, gastroparesis, and intestinal obstruction were not eligible for the study. Patient characteristics including age, gender, primary diagnosis, history of heavy alcohol intake, chemotherapy regimen administered , number of cycles, and Eastern Cooperative Group performance status at the start of therapy were noted. Primary outcome was the complete control of platinum-induced acute nausea and vomiting. Secondary outcome measures included control of > or = grade 1 nausea or vomiting, comparison of two doses of dexamethasone, and antiemetic eficacy among various platinum drugs. National Cancer Institute Common Toxicity Criteria version 2.0 was used to assess toxicity. RESULTS: A total of 126 patients received 369 cycles of platinum-based therapy. Dolasetron ( n=157), granisetron ( n=81), and ondansetron ( n=131) achieved complete control of vomiting in 89.8, 95.5, and 92.3% (p=0.67) of cycles, respectively. Respectively, complete nausea control was observed in 68.1, 75.3 and, 69.4% (p=0.50). Dexamethasone 20 mg was not superior to 10 mg in complete control of nausea and vomiting ( p= 0.15 and p=0.63, respectively). However, complete nausea control was signinficantly better in the subgroup of patients getting cisplatin-compared with carboplatin-based regimens (78.8% vs. 67.7%, p<0.05). CONCLUSION: No significant difference exists in the antiemetic efficacy of the three 5-HT(3) antagonists studied in controlling CINV when administered in combination with dexamethasone. Choicce of antiemetic regimen should therefore be based on drug cost. PMID- 17873108 TI - Low-molecular-weight heparin in cancer-associated thrombosis: treatment, secondary prevention, and survival. AB - OBJECTIVES: Venous thromboembolism (VTE) occurs more frequently in cancer patients than in non-cancer patients and outcomes are poor in patients with both cancer and thrombosis. Patients with cancer who develop thrombosis are more likely to experience a recurrence of VTE and have increased bleeding complications while receiving oral anticoagulant treatment. The purpose of this paper is to discuss the causes and outcomes of thrombosis in cancer patients, the limitations of warfarin therapy, the guidelines and data for the use of low molecular-weight heparins (LMWHs) in the treatment and secondary prevention of thrombosis in cancer patients, and emerging data regarding survival with the use of LMWH in cancer patients. METHODS: Literature for this paper has been collected using multiple sources, including primary, secondary, and tertiary references. Online searches have been conducted utilizing the PubMed and OVID databases, and abstracts from the Proceedings of the American Society of Clinical Oncology and the American Society of Hematology Annual Meeting and Exhibition. The following key terms were used in the search: cancer, deep vein thrombosis, pulmonary embolism, anticoagulation, LMWHs, guidelines, survival, cost. RESULTS: The long term use of LMWHs in the settings of cancer and thrombosis are supported by recent clinical trial evidence that demonstrate their equivalent safety and improved efficacy when compared to oral anticoagulants resulting in their inclusion in current guidelines. Finally, newer studies offer further evidence of improved outcomes with dalteparin and nadroparin, including possible survival benefits. CONCLUSIONS: Treatment with LMWHs has been shown to be more effective than warfarin in the extended treatment of VTE in patients with cancer and is safe in this setting. Use of a LMWH for at least the first 3-6 months of long term treatment is now considered the standard of care for patients with cancer and is recommended in numerous guidelines. Additionally, further evaluation of the survival benefits of LMWH in cancer patients is warranted. PMID- 17873109 TI - Long-term stability of sodium folinate in dextrose 5% polyolefin bags at 4degreesC. AB - OBJECTIVES: Preparation of intravenous solutions in advance could be an efficient approach to improve quality assurance, security, time management, and cost saving of drug provision. The purpose of this paper is to investigate the stability of sodium folinate solutions at 3.2 mg mL-1 in 5% dextrose polyolefin bags at 4degreesC. METHODS: The stability of five polyolefin bags of solution containing approximately 3.2 mg mL-1 of sodium folinate in 5% dextrose prepared under aseptic conditions and stored at 48degreesC have been studied over 30 days. Sodium folinate concentrations have been measured by high performance liquid chromatography and the results have been analysed by regression analysis. Solutions have been visually inspected and pH measured. RESULTS: No colour change or precipitation occurred in the preparations. Based on a shelf-life of 90% residual potency, sodium folinate solutions have been observed to be stable for a period of at least 30 days at 4degreesC, where lower confidence limits of the results value remain above 90% of the initial concentration. During this stability period, the pH values of infusions have been observed to decrease slightly without affecting chromatographic parameters. CONCLUSION: Within these limits, sodium folinate in 5% dextrose infusion may be prepared and stored in advance by a centralized intravenous admixture service. PMID- 17873110 TI - Liposomal doxorubicin-associated acute hypersensitivity despite appropriate preventive measures. AB - Liposomal doxorubicin is becoming popular as a chemotherapeutic agent in the treatment of multiple malignancies. This paper describes an episode of hypersensitivity reaction associated with the infusion of liposomal doxorubicin in an ovarian cancer patient, despite preventive measures being undertaken during her first cycle of chemotherapy. Clinicians may overlook the possibility of hypersensitivity reactions associated with liposomal doxorubicin because routine prophylaxis is not provided and reactions are infrequently observed in practice. Close monitoring during the first 15 min of infusion for signs of hypersensitivity should be mandatory for patients receiving their first dose of liposomal doxorubicin. Further research should identify patients who are at risk of experiencing such hypersensitivity. PMID- 17873111 TI - Dose-banding of carboplatin: rationale and proposed banding scheme. AB - BACKGROUND: In dose-banding (DB) prescribed doses of cancer chemotherapy are fitted to doseranges or 'bands' and standard doses for each band are provided using a selection of pre-filled infusions or syringes, either singly or in combination. DB is used for several drugs where dose is based on body surface area. No DB-scheme has been reported for carboplatin, which, in clinical practice, is routinely dosed according to renal function. STUDY OBJECTIVE: To assess the rationale for DB of carboplatin with regards to factors that influence dosing accuracy, develop a DB scheme, and discuss its potential use and limitations. METHODS: Prospective evaluations of carboplatin area under the plasma concentration -- time curve (AUC) following application of the Calvert formula were identified by a literature search. A relevant carboplatin dose range for construction of a DB-scheme with Calvert-formula based doses was obtained from published glomerular filtration rate distributions for patients receiving carboplatin. RESULTS: A DB-scheme was developed for individually calculated carboplatin doses of 358-1232 mg, with 35 mg increments between each standard dose and a maximum deviation of 4.7% from prescribed dose. The proposed DB-scheme covers the GFR-ranges 47-221 mL/min and 26-151 mL/min for patients receiving doses based on the target AUCs of 5 and 7 mg/mL/min, respectively. CONCLUSION: There is a strong scientific rationale to support DB of carboplatin. The proposed banding scheme could introduce benefits to patients and healthcare staff but, as with other DB schemes, should be validated with prospective clinical and pharmacokinetic studies to confirm safety and efficacy. PMID- 17873112 TI - A sequential temperature cycling study for the investigation of carboplatin infusion stability to facilitate 'dose-banding'. AB - STUDY OBJECTIVE: To determine the physical and chemical stability of carboplatin infusion for dosebanding, with cycling between refrigerated storage and room temperature in-use conditions. DESIGN: A sequential study design was selected to closely simulate the temperatures and conditions experienced by drug infusions in pharmaceutical storage and in clinical use. Carboplatin infusions, 0.70 and 2.15 mg/mL, were stored refrigerated for up to 84 days, followed by incubation at 25degreesC for 24 h. The infusions were also returned to refrigerated storage for 3 and 7 days, to replicate a situation in which returned, unused infusions are kept for re-issuing. On pre-determined time-points, infusion chemical and physical stability were determined by HLPC, sub-visual particulate counts, pH measurement, and weighing of infusions. RESULTS: Light protected carboplatin infusions at both study concentrations were chemically and physically stable following refrigerated storage for 84 days, followed by a further 24 h under 'in use' conditions at 25degreesC. Additionally, the infusions were stable following return to refrigerated storage again for at least 7 days. CONCLUSION: This study has demonstrated extended stability of carboplatin infusions which enables batch scale preparation of standard infusions for dose-banding schemes. PMID- 17873113 TI - Nestin expression in different tumours and its relevance to malignant grade. AB - BACKGROUND: Nestin, an intermediate filament (IF) protein, is expressed in proliferating progenitor cells of developmental and regenerating tissues, and is identified as a neuroepithelial precursor cell marker. Recently, nestin was detected in some neoplasms such as glioma, ependymoma, melanoma, rhabdomyosarcoma, gastrointestinal stromal tumour (GIST), and testicular stromal tumour. Moreover, the expression intensity of nestin exhibited significant correlation with the malignant grade of glioma. AIMS: To detect the expression of nestin in different tumours and to analyse the relationship between the expression of nestin and the malignant grade of the tumours. METHODS: Formalin fixed and paraffin-embedded surgical samples of neoplastic tissues were obtained from the Department of Pathology of Sun Yat-sen University. Histological analysis and immunohistochemical staining for nestin were performed. Histoscores were analysed by semi-quantitative evaluation. RESULTS: Nestin was expressed predominantly in the cytoplasm of angiosarcoma, pancreatic adenocarcinoma and GIST samples, and some tumour cells expressed in the nucleus. There was a statistically significant difference between the histoscore of nestin in high malignant GIST (2.2366 (0.6920)) and that in low malignant GIST (1.3783 (0.4268)) (p = 0.003); and also between that in high malignant angiosarcoma (1.9188 (0.2069)) and that in low malignant angiosarcoma (0.6474 (0.3273)) (p = 0.000). Cavernous angioma did not express nestin. The histoscore of nestin in high malignant pancreatic adenocarcinoma (7/14) was 1.1767 (0.4676), and that in low malignant pancreatic adenocarcinoma (3/8) was 0.6577 (0.0056) (no significant difference, p = 0.112). CONCLUSIONS: Results suggest that the expression of nestin may play an important role in the development of some neoplasms such as GIST and angiosarcoma. PMID- 17873114 TI - Mucinous breast lesions: diagnostic challenges. AB - Breast lesions with mucin represent a broad spectrum of entities, ranging from benign fibrocystic changes with luminal mucin to mucocele-like lesions (MLL), which can be associated with banal epithelial alterations, atypical ductal hyperplasia or ductal carcinoma in situ. Occasionally invasive mucinous carcinoma can be identified in contiguity with MLL. Diagnostic challenges are enumerated, histological differentials are discussed, and a practical approach towards resolving some of these issues is provided. In addition to these lesions with abundant extracellular mucin, there are also conditions that feature stromal mucinous or myxoid material, as well as rare entities that demonstrate both epithelial extracellular and stromal mucin. PMID- 17873115 TI - Enterovirus infection of the stomach in chronic fatigue syndrome/myalgic encephalomyelitis. PMID- 17873116 TI - Epstein Barr virus-associated tumours: an update for the attention of the working pathologist. AB - Epstein-Barr virus (EBV) is a herpesvirus associated with approximately 1% of tumours worldwide. EBV is the epitome of B lymphotropic viruses, but the spectrum of tumours it is associated with extends to T lymphocyte and NK cell malignancies, various types of carcinomas and smooth muscle tumours. Ubiquitous EBV infection in humans implies that most individuals carry EBV-infected cells. Therefore, mere detection of the virus in individuals with a tumour is not sufficient for establishing a causal relationship between both events, but instead requires unequivocal detection of viral nucleic acids or viral proteins in the tumour cells. Recent controversies about EBV infection in several carcinomas mainly resulted from such technical issues. The gold standard remains in situ EBER detection, but detection of EBNA1 would be an interesting alternative. EBV detection can be helpful for diagnostic, prognostic and therapeutic purposes. The rate of EBV association with entities such as NK/T cell tumours of the nasal type is so high that absence of detection of the virus in such a lesion should cast doubt of the accuracy of the diagnosis. Similarly, diagnosis of EBV-associated follicular pseudo-tumour obviously requires detection of the virus. EBV-positive common gastric adenocarcinomas seem to have a better prognosis than their EBV-negative counterparts and identification of the virus in B cell lymphoproliferations in immunocompromised individuals will guide therapeutic options. In conclusion, EBV-associated tumours are common enough to be relevant for the pathologist in everyday practice, but there is a need to facilitate detection of the virus (eg EBNA1 antibody). PMID- 17873117 TI - Genotype-phenotype correlation in 21 patients with Wolf-Hirschhorn syndrome using high resolution array comparative genome hybridisation (CGH). AB - BACKGROUND: The Wolf-Hirschhorn syndrome (WHS) is usually caused by terminal deletions of the short arm of chromosome 4 and is phenotypically defined by growth and mental retardation, seizures, and specific craniofacial manifestations. Large variation is observed in phenotypic expression of these features. In order to compare the phenotype with the genotype, we localised the breakpoints of the 4 pter aberrations using a chromosome 4 specific tiling BAC/PAC array. METHODS: In total, DNA from 21 patients was analysed, of which 8 had a cytogenetic visible and 13 a submicroscopic deletion. RESULTS AND CONCLUSION: In addition to classical terminal deletions sized between 1.9 and 30 Mb, we observed the smallest terminal deletion (1.4 Mb) ever reported in a patient with mild WHS stigmata. In addition, we identified and mapped interstitial deletions in four patients. This study positions the genes causing microcephaly, intrauterine and postnatal growth retardation between 0.3 and 1.4 Mb and further refines the regions causing congenital heart disease, cleft lip and/or palate, oligodontia, and hypospadias. PMID- 17873118 TI - Genotype-phenotype study of familial haemophagocytic lymphohistiocytosis due to perforin mutations. AB - BACKGROUND: PRF1 gene mutations are associated with familial haemophagocytic lymphohistiocytosis type 2 (FHL2). Genotype-phenotype analysis, previously hampered by limited numbers of patients, was for the first time performed by data pooling from five large centres worldwide. PATIENTS AND METHODS: Members of the Histiocyte Society were asked to report cases of FHL2 on specific forms. Data were pooled in a common database and analysed. RESULTS: The 124 patients had 63 different mutations (including 15 novel mutations): 11 nonsense, 10 frameshift, 38 missense and 4 in-frame deletions. Some mutations were found more commonly: 1122 G-->A (W374X), associated with Turkish origin, in 32 patients; 50delT (L17fsX22) associated with African/African American origin, in 21 patients; and 1090-91delCT (L364fsX), in 7 Japanese patients. Flow cytometry showed that perforin expression was absent in 40, reduced in 6 and normal in 4 patients. Patients presented at a median age of 3 months (quartiles: 2, 3 and 13 months), always with fever, splenomegaly and thrombocytopenia. NK activity was absent in 36 (51%), 5% in 4 (6%), "reduced" in 2 (3%) (not reported, n = 54). Nonsense mutations were significantly associated with younger age at onset (p<0.001) and absent natural killer activity (p = 0.008). CONCLUSION: PRF1 mutations are spread over the functional domains. Specific mutations are strongly associated with Turkish, African American and Japanese ethnic groups. Later onset and residual cytotoxic function are observed in patients with at least one missense mutation. PMID- 17873119 TI - High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome. AB - BACKGROUND: In patients with juvenile polyposis syndrome (JPS) the frequency of large genomic deletions in the SMAD4 and BMPR1A genes was unknown. METHODS: Mutation and phenotype analysis was used in 80 unrelated patients of whom 65 met the clinical criteria for JPS (typical JPS) and 15 were suspected to have JPS. RESULTS: By direct sequencing of the two genes, point mutations were identified in 30 patients (46% of typical JPS). Using MLPA, large genomic deletions were found in 14% of all patients with typical JPS (six deletions in SMAD4 and three deletions in BMPR1A). Mutation analysis of the PTEN gene in the remaining 41 mutation negative cases uncovered a point mutation in two patients (5%). SMAD4 mutation carriers had a significantly higher frequency of gastric polyposis (73%) than did patients with BMPR1A mutations (8%) (p<0.001); all seven cases of gastric cancer occurred in families with SMAD4 mutations. SMAD4 mutation carriers with gastric polyps were significantly older at gastroscopy than those without (p<0.001). In 22% of the 23 unrelated SMAD4 mutation carriers, hereditary hemorrhagic telangiectasia (HHT) was also diagnosed clinically. The documented histologic findings encompassed a wide distribution of different polyp types, comparable with that described in hereditary mixed polyposis syndromes (HMPS). CONCLUSIONS: Screening for large deletions raised the mutation detection rate to 60% in the 65 patients with typical JPS. A strong genotype-phenotype correlation for gastric polyposis, gastric cancer, and HHT was identified, which should have implications for counselling and surveillance. Histopathological results in hamartomatous polyposis syndromes must be critically interpreted. PMID- 17873120 TI - Dissection of the aorta in Turner syndrome: two cases and review of 85 cases in the literature. AB - Girls and women with Turner syndrome are at risk for catastrophic aortic dissection and rupture, but the clinical profile for those at risk is not well described. In addition to reporting two new cases, we performed an electronic search to identify all reported cases of aortic dissection associated with Turner syndrome. Particular attention was paid to the reporting of systemic hypertension (HTN) and congenital heart disease (CHD) which are known risk factors for aortic disease in the general population. In total, 85 cases of aortic dissection in TS were reported between 1961 and 2006. Dissection occurred at a young age, 30.7 (range 4-64) years, which is significantly earlier than its occurrence in the general female population (68 years). Of the cases for which HTN and CHD were explicitly assessed, 15% had HTN alone, 30% had CHD alone and 34% had both. Importantly, in 11% of the cases, neither HTN nor CHD were identified, suggesting that TS alone is an independent risk factor for aortic dissection; however, the cases where no risk factors were identified were very poorly documented. Dissection in women with TS undergoing assisted reproductive techniques (ART) frequently resulted in death. The literature on aortic dissection in TS is sparse and most cases are poorly documented, making it difficult to establish firm guidelines regarding monitoring and treatment. A TS aortic dissection registry has been established to better determine the natural history and risk factors (http://www.tssus.org/readweb.asp?wid = 3092). PMID- 17873122 TI - Antenatal mitochondrial disease caused by mitochondrial ribosomal protein (MRPS22) mutation. AB - Three patients born to the same set of consanguineous parents presented with antenatal skin oedema, hypotonia, cardiomyopathy and tubulopathy. The enzymatic activities of multiple mitochondrial respiratory chain complexes were reduced in muscle. Marked reduction of 12s rRNA, the core of the mitochondrial small ribosomal subunit, was found in fibroblasts. Homozygosity mapping led to the identification of a mutation in the MRPS22 gene, which encodes a mitochondrial ribosomal protein. Transfection of the patient cells with wild-type MRPS22 cDNA increased the 12s rRNA content and normalised the enzymatic activities. Quantification of mitochondrial transcripts is advisable in patients with multiple defects of the mitochondrial respiratory chain. PMID- 17873121 TI - Identification of novel candidate genes associated with cleft lip and palate using array comparative genomic hybridisation. AB - AIM AND METHOD: We analysed DNA samples isolated from individuals born with cleft lip and cleft palate to identify deletions and duplications of candidate gene loci using array comparative genomic hybridisation (array-CGH). RESULTS: Of 83 syndromic cases analysed we identified one subject with a previously unknown 2.7 Mb deletion at 22q11.21 coinciding with the DiGeorge syndrome region. Eighteen of the syndromic cases had clinical features of Van der Woude syndrome and deletions were identified in five of these, all of which encompassed the interferon regulatory factor 6 (IRF6) gene. In a series of 104 non-syndromic cases we found one subject with a 3.2 Mb deletion at chromosome 6q25.1-25.2 and another with a 2.2 Mb deletion at 10q26.11-26.13. Analyses of parental DNA demonstrated that the two deletion cases at 22q11.21 and 6q25.1-25.2 were de novo, while the deletion of 10q26.11-26.13 was inherited from the mother, who also has a cleft lip. These deletions appear likely to be causally associated with the phenotypes of the subjects. Estrogen receptor 1 (ESR1) and fibroblast growth factor receptor 2 (FGFR2) genes from the 6q25.1-25.2 and 10q26.11-26.13, respectively, were identified as likely causative genes using a gene prioritization software. CONCLUSION: We have shown that array-CGH analysis of DNA samples derived from cleft lip and palate subjects is an efficient and productive method for identifying candidate chromosomal loci and genes, complementing traditional genetic mapping strategies. PMID- 17873123 TI - Hematopoietic cell transplantation specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences. AB - A new hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was effective in predicting outcomes among patients with hematologic malignancies who underwent HCT at Fred Hutchinson Cancer Research Center (FHCRC). Here, we compared the performance of the HCT-CI to 2 other indices and then tested its capacity to predict outcomes among 2 cohorts of patients diagnosed with a single disease entity, acute myeloid leukemia in first complete remission, who underwent transplantation at either FHCRC or M. D. Anderson Cancer Center (MDACC). FHCRC patients less frequently had unfavorable cytogenetics (15% versus 36%) and HCT-CI scores of 3 or more (21% versus 58%) compared with MDACC patients. We found that the HCT-CI had higher sensitivity and outcome predictability compared with the other indices among both cohorts. HCT-CI scores of 0, 1 to 2, and 3 or more predicted comparable nonrelapse mortality (NRM) among FHCRC and MDACC patients. In multivariate models, HCT-CI scores were associated with the highest hazard ratios (HRS) for NRM and survival among each cohort. The 2-year survival rates among FHCRC and MDACC patients were 71% versus 56%, respectively. After adjustment for risk factors, including HCT-CI scores, no difference in survival was detected (HR: 0.98, P = .94). The HCT-CI is a sensitive and informative tool for comparing trial results at different institutions. Inclusion of comorbidity data in HCT trials provides valuable, independent information. PMID- 17873124 TI - Spatial and temporal heterogeneity of regional myocardial uptake in patients without heart disease under fasting conditions on repeated whole-body 18F-FDG PET/CT. AB - Imaging of cardiac (18)F-FDG uptake is used in the diagnostic evaluation of residual viable myocardium. Although, originally, hibernating myocardium was identified by a mismatch between perfusion defect and relatively preserved (18)F FDG uptake, at present several studies propose that (18)F-FDG distribution can also be used alone for this purpose. Nevertheless, even severe myocardial (18)F FDG uptake defects are frequently observed in cancer patients without any cardiac disease. The aim of this study was to retrospectively analyze global and regional (18)F-FDG cardiac images of 49 consecutive cancer patients free of cardiac diseases who submitted to 3 PET scans under fasting conditions. METHODS: Images were acquired with a high-resolution PET/CT scanner. Three-dimensional regions of interest were drawn on the fused PET/CT images to measure the maximal standardized uptake value of the left ventricular myocardium (SUV(Myo)) as well as the average SUV of the left ventricular blood (SUV(LV)) and of the liver (SUV(Liver)). Analysis of regional myocardial (18)F-FDG uptake was performed on a subsample of 26 patients by an automatic recognition of endocardial and epicardial borders and subdividing the left ventricle in 20 segments. Regional (18)F-FDG distribution was defined as the percentage of SUV(Myo) in each region. RESULTS: SUV(Myo) as well as SUV(LV) and SUV(Liver) did not change on average throughout the studies. This stability was not caused by a persistent pattern of myocardial (18-)FDG distribution. Rather, it was associated with important variations in both directions over time. Regional (18)F-FDG distribution was largely heterogeneous in all 3 studies, with a variation coefficient in each patient of 18% +/- 7%, 18% +/- 5%, and 17% +/- 5%, respectively. An (18)F-FDG uptake of <50% occurred in 78, 102, and 69 of 468 segments, although it disappeared in 55% of instances at subsequent examinations. Regional temporal variability was also marked: The absolute value of the difference in percent uptake was 10.1% +/- 7.3% from test 1 to test 2, 8.0% +/- 7.0% from test 1 to test 3, and 9.2% +/- 6.9% from test 2 to test 3. Overall from one test to another, uptake increased or decreased by >10% in 76 and in 116 of 468 segments, respectively. CONCLUSION: The large spatial and temporal heterogeneity of the myocardial metabolic pattern, in cancer patients free of any disease, suggests a word of caution on the use of (18)F-FDG alone as a diagnostic tool for myocardial viability. PMID- 17873125 TI - Presence of specific 11C-meta-Hydroxyephedrine retention in heart, lung, pancreas, and brown adipose tissue. AB - (11)C-meta-Hydroxyephedrine (HED) is used in cardiac PET as an index of norepinephrine (NE) reuptake transporter (NET) density and synaptic NE levels. Whereas cardiac uptake is well documented, tracer retention in other tissues with rich noradrenergic innervation is unclear. Dysfunctional sympathetic nervous system (SNS) function in extracardiac metabolic storage tissues (i.e., adipose tissue and skeletal muscle) and endocrine organs contributes to several disorders. The aim of this study was to determine the potential of HED as an index of NE function in brown adipose tissue, lung, pancreas, skeletal muscle, and kidney by identifying NET-specific retention and determining the presence of radiolabeled metabolites. METHODS: Male Sprague-Dawley rats were administered HED and sacrificed at 30 min after tracer injection. Tissues were rapidly excised and counted for radioactivity, and relative tracer retention was quantified. Pretreatment with NET inhibitors established specific HED accumulation. The effect of elevated NE was tested by subcutaneous minipump NE infusion or inhibition of monoamine oxidase. Column-switch high-performance liquid chromatography (HPLC) was used to analyze the presence of radiolabeled metabolites in heart, brown adipose tissue, pancreas, and plasma. RESULTS: NET specific retention was observed in heart, brown adipose tissue, lung, and pancreas but not in liver, skeletal muscle, or kidney. A dose-dependent response of HED accumulation to treatments elevating NE levels was established in tissues exhibiting specific uptake. At 30 min after tracer administration, HPLC analysis revealed 93%-95% of total radioactivity signal derived from unchanged HED in heart, pancreas, and brown adipose tissue compared with 61% +/- 8% unchanged HED in plasma. CONCLUSION: In addition to the heart, lung, pancreas, and brown adipose tissue exhibit specific and NE-responsive uptake of HED, supporting the potential for novel PET studies of SNS integrity in these tissues. PMID- 17873126 TI - Feasibility and diagnostic accuracy of a gated SPECT early-imaging protocol: a multicenter study of the Myoview Imaging Optimization Group. AB - The aim of this study was to investigate whether early (time 1, or T1) myocardial tetrofosmin imaging is feasible and as accurate in detecting coronary artery disease as is standard delayed (time 2, or T2) imaging. METHODS: One hundred twenty patients (100 men and 20 women; mean age +/- SD, 61 +/- 10 y) with anginal symptoms underwent tetrofosmin gated SPECT. Stress/rest T1 imaging was performed at 15 min and T2 at 45 min after injection. Image quality was visually evaluated using a 4-point scale (from 0 = poor to 3 = optimal). Myocardial perfusion analysis was performed on a 20-segment model using quantitative perfusion SPECT software, and reversible ischemia was scored as a summed difference score (SDS). Coronary angiography was performed within 1 mo on all patients, and stenosis of more than 50% of the diameter was considered significant. RESULTS: Overall, quality was scored as optimal or good for 94% of T1 images and 95% of T2 images (P = not statistically significant). Heart, lung, liver, and subdiaphragmatic counts did not differ for stress and rest T1 and T2 imaging. A good linear relationship was seen between T1 and T2 SDS (r = 0.69; P < 0.0001), and Bland Altman analysis showed good agreement between the 2 conditions. In terms of global diagnostic accuracy, areas under the receiver-operating-characteristic curve were comparable between T1 and T2 (0.80 vs. 0.81, P = not statistically significant). Discrepancies between T1 and T2 SDS were observed in 44% of patients (T1 - T2 SDS > 2). Linear regression analysis showed a good correlation between T1 and T2 SDS (r = 0.67; P < 0.0001), whereas the Bland-Altman method showed a shift in the mean value of the difference of +2.67 +/- 2.73. In patients with a T1 - T2 SDS of more than 2, areas under the receiver-operating characteristic curves were significantly higher for T1 than for T2 images (0.79 vs. 0.70, P < 0.001). CONCLUSION: T1 imaging is feasible and as accurate as T2 imaging in identifying coronary artery disease. However, in a discrete subset of patients, early acquisition strengthens the clinical message of defect reversibility by permitting earlier, more accurate identification of more severe myocardial ischemia. PMID- 17873127 TI - The role of interval nodes in sentinel lymph node mapping and dissection for melanoma patients. AB - In sentinel node (SN) biopsy, an interval SN is defined as a lymph node or group of lymph nodes located between the primary melanoma and an anatomically well defined lymph node group directly draining the skin. As shown in previous reports, these interval SNs seem to be at the same metastatic risk as are SNs in the usual, classic areas. This study aimed to review the incidence, lymphatic anatomy, and metastatic risk of interval SNs. METHODS: SN biopsy was performed at a tertiary center by a single surgical team on a cohort of 402 consecutive patients with primary melanoma. The triple technique of localization was used that is, lymphoscintigraphy, blue dye, and gamma-probe. Otolaryngologic melanoma and mucosal melanoma were excluded from this analysis. SNs were examined by serial sectioning and immunohistochemistry. All patients with metastatic SNs were recommended to undergo a radical selective lymph node dissection. RESULTS: The primary locations of the melanomas included the trunk (188), an upper limb (67), or a lower limb (147). Overall, 97 (24.1%) of the 402 SNs were metastatic. Interval SNs were observed in 18 patients, in all but 2 of whom classic SNs were also found. The location of the primary was truncal in 11 (61%) of the 18, upper limb in 5, and lower limb in 2. One patient with a dorsal melanoma had drainage exclusively in a cervicoscapular area that was shown on removal to contain not lymph node tissue but only a blue lymph channel without tumor cells. Apart from the interval SN, 13 patients had 1 classic SN area and 3 patients 2 classic SN areas. Of the 18 patients, 2 had at least 1 metastatic interval SN and 2 had a classic SN that was metastatic; overall, 4 (22.2%) of 18 patients were node positive. CONCLUSION: We found that 2 of 18 interval SNs were metastatic: This study showed that preoperative lymphoscintigraphy must review all known lymphatic areas in order to exclude an interval SN. PMID- 17873128 TI - 123I-5-IA-85380 SPECT imaging of nicotinic acetylcholine receptor availability in nonsmokers: effects of sex and menstrual phase. AB - The study of the effects of sex and hormones on brain chemistry and neurotransmission is of increasing importance as evidence emerges of sex differences in behavioral symptoms and treatment response in neuropsychiatric disorders. The nicotinic acetylcholine receptor (nAChR) system has been implicated in a variety of psychiatric disorders, including tobacco smoking, for which there is strong evidence supporting sex differences in behaviors and response to smoking cessation treatments. We examined the availability of nAChR containing the beta(2) subunit in healthy men and women and the influence of menstrual phase among women. METHODS: Ten men and 19 women nonsmokers underwent one (123)I-5-IA-85380 ((123)I-5-IA) SPECT scan and one MRI scan. A subset of 9 women, aged 18-39 y, underwent a second (123)I-5-IA scan. These 9 women were scanned during the early follicular (days 4-7 in 8 subjects and day 11 in 1 subject) and mid-luteal (days 19-25) phases of their menstrual cycle. Hormone levels were measured in all women to confirm the phase of the cycle. RESULTS: Regional brain activity (kBq/cm(3)) was higher (39%-54%) in women than in men nonsmokers. When regional brain activity was normalized to total plasma parent to correct for individual differences in radiotracer metabolism (V(T)'), differences of 10%-16% were observed, with women greater than men. In contrast, when regional brain activity was normalized to free plasma parent (V(T)), there was less than a 4% difference by sex in regional brain beta(2)-nAChR availability. These sex differences in kBq/cm(3) and V(T)' resulted from significantly higher levels of total plasma parent, free fraction (f(1)), and free plasma parent in women than in men nonsmokers. No differences in plasma measures or brain beta(2)-nAChR availability were observed across the menstrual cycle for any outcome measure. CONCLUSION: Overall, these findings demonstrate no significant difference in brain beta(2)-nAChR availability between men and women nonsmokers or across the menstrual cycle. Importantly, these findings demonstrate sex differences in radiotracer metabolism and plasma protein binding and highlight the critical need to measure plasma radiotracer levels and f(1) in studies that include both sexes. PMID- 17873129 TI - Early 18F-FDG PET for prediction of prognosis in patients with diffuse large B cell lymphoma: SUV-based assessment versus visual analysis. AB - The purpose of this study was to assess the prognostic value of early (18)F-FDG PET using standardized uptake value (SUV) compared with visual analysis in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Ninety-two patients with newly diagnosed DLBCL underwent (18)F-FDG PET prospectively before and after 2 cycles of chemotherapy (at midtherapy). Maximum SUV (SUVmax) and mean SUV (SUVmean) normalized to body weight and body surface area, as well as tumor-to normal ratios, were computed on the most intense uptake areas. The SUVs, tumor-to normal ratios, and their changes over time were compared with visual analysis for predicting event-free survival (EFS) and overall survival, using receiver operating-characteristic (ROC) analysis. Survival curves were estimated with Kaplan-Meier analysis and compared using the log-rank test. RESULTS: With visual analysis, the accuracy of early PET to predict EFS was 65.2%. The 2-y estimate for EFS was 51% (95% confidence interval [CI], 34%-68%) in the PET-positive group compared with 79% (95% CI, 68%-90%) in the PET-negative group (P = 0.009). An optimal cutoff value of 65.7% SUVmax reduction from baseline to midtherapy obtained from ROC analysis yielded an accuracy of 76.1% to predict EFS. The 2-y estimate for EFS was 21% (95% CI, 0%-42%) in patients with SUVmax reduction 65.7% (P < 0.0001). Fourteen patients considered as positive on visual analysis could have been reclassified as good responders. CONCLUSION: SUV-based assessment of therapeutic response during first-line chemotherapy improves the prognostic value of early (18)F-FDG PET compared with visual analysis in DLBCL. PMID- 17873130 TI - 18F-FDOPA kinetics in brain tumors. AB - L-3,4-Dihydroxy-6-(18)F-fluoro-phenyl-alanine ((18)F-FDOPA) is an amino acid analog used to evaluate presynaptic dopaminergic neuronal function. Evaluation of tumor recurrence in neurooncology is another application. Here, the kinetics of (18)F-FDOPA in brain tumors were investigated. METHODS: A total of 37 patients underwent 45 studies; 10 had grade IV, 10 had grade III, and 13 had grade II brain tumors; 2 had metastases; and 2 had benign lesions. After (18)F-DOPA was administered at 1.5-5 MBq/kg, dynamic PET images were acquired for 75 min. Images were reconstructed with iterative algorithms, and corrections for attenuation and scatter were applied. Images representing venous structures, the striatum, and tumors were generated with factor analysis, and from these, input and output functions were derived with simple threshold techniques. Compartmental modeling was applied to estimate rate constants. RESULTS: A 2-compartment model was able to describe (18)F-FDOPA kinetics in tumors and the cerebellum but not the striatum. A 3-compartment model with corrections for tissue blood volume, metabolites, and partial volume appeared to be superior for describing (18)F FDOPA kinetics in tumors and the striatum. A significant correlation was found between influx rate constant K and late uptake (standardized uptake value from 65 to 75 min), whereas the correlation of K with early uptake was weak. High-grade tumors had significantly higher transport rate constant k(1), equilibrium distribution volumes, and influx rate constant K than did low-grade tumors (P < 0.01). Tumor uptake showed a maximum at about 15 min, whereas the striatum typically showed a plateau-shaped curve. Patlak graphical analysis did not provide accurate parameter estimates. Logan graphical analysis yielded reliable estimates of the distribution volume and could separate newly diagnosed high grade tumors from low-grade tumors. CONCLUSION: A 2-compartment model was able to describe (18)F-FDOPA kinetics in tumors in a first approximation. A 3-compartment model with corrections for metabolites and partial volume could adequately describe (18)F-FDOPA kinetics in tumors, the striatum, and the cerebellum. This model suggests that (18)F-FDOPA was transported but not trapped in tumors, unlike in the striatum. The shape of the uptake curve appeared to be related to tumor grade. After an early maximum, high-grade tumors had a steep descending branch, whereas low-grade tumors had a slowly declining curve, like that for the cerebellum but on a higher scale. PMID- 17873131 TI - The dental safety profile of high-dose radioiodine therapy for thyroid cancer: long-term results of a longitudinal cohort study. AB - The long-term dental safety profile of high-dose radioiodine therapy remained elusive despite more than 6 decades of clinical use. METHODS: In a cohort study, we investigated the incidence of sialadenitis, xerostomia, caries, and tooth extractions after high-dose radioiodine therapy for differentiated thyroid cancer and explored risk factors by multiple regression models. RESULTS: One hundred seventy-six participants were recruited (median follow-up, 6.6 y; range, 1.1-32.6 y; patient-years: 8,472 before and 1,421 after radioiodine therapy). Scintigraphic salivary gland uptake during radioiodine treatment predicted development of sialadenitis (odds ratio: 1.31 [1.05-1.63], P = 0.015) and xerostomia (odds ratio: 1.58 [1.16-2.16], P = 0.004). The caries risk increased by postradioiodine xerostomia (% increase: 98.8 [26.5-212], P = 0.003). The long term risk for postradioiodine tooth extractions increased with increasing cumulative radioiodine activities (% increase [per gigabequerel]: 8.14 [1.07, 15.7], P = 0.02). CONCLUSION: High-dose radioiodine treatment can impair the long term dental health, depending on the cumulative radioiodine activity and individual salivary gland radioiodine uptake. PMID- 17873132 TI - The effects of carbidopa on uptake of 6-18F-Fluoro-L-DOPA in PET of pheochromocytoma and extraadrenal abdominal paraganglioma. AB - 6-(18)F-fluoro-l-3,4-dihydroxyphenylalanine ((18)F-DOPA) PET is a useful tool for the detection of certain neuroendocrine tumors, especially with the preadministration of carbidopa, an inhibitor of DOPA decarboxylase. Whether carbidopa also improves (18)F-DOPA PET of adrenal pheochromocytomas and extraadrenal paragangliomas is unknown. The aim of this study was to investigate the sensitivity of (18)F-DOPA PET in the detection of paraganglioma and its metastatic lesions and to evaluate whether tracer uptake by the tumors is enhanced by carbidopa. METHODS: Two patients with nonmetastatic adrenal pheochromocytoma, and 9 patients with extraadrenal abdominal paraganglioma (1 nonmetastatic, 8 metastatic), underwent whole-body CT, MRI, baseline (18)F-DOPA PET, and (18)F-DOPA PET with oral preadministration of 200 mg of carbidopa. The dynamics of tracer uptake by these lesions and the physiologic distribution of (18)F-DOPA in normal tissues were recorded. RESULTS: Seventy-eight lesions were detected by CT or MRI, 54 by baseline (18)F-DOPA PET (P = 0.0022 vs. CT/MRI), and 57 by (18)F-DOPA PET plus carbidopa (P = 0.0075 vs. CT/MRI, not statistically significant vs. baseline). In reference to findings on CT and MRI, the sensitivities of baseline (18)F-DOPA PET were 47.4% for lesions and 55.6% for positive body regions, versus 50.0% (lesions) and 66.7% (regions) for (18)F-DOPA PET plus carbidopa (neither is statistically significant vs. baseline). Compared with baseline, carbidopa detected additional lesions in 3 (27%) of 11 patients. Carbidopa increased the mean (+/-SD) peak standardized uptake value in index tumor lesions from 6.4 +/- 3.9 to 9.1 +/- 5.6 (P = 0.037). Pancreatic physiologic (18)F-DOPA uptake, which may mask adrenal pheochromocytoma, is blocked by carbidopa. CONCLUSION: Carbidopa enhances the sensitivity of (18)F-DOPA PET for adrenal pheochromocytomas and extraadrenal abdominal paragangliomas by increasing the tumor-to-background ratio of tracer uptake. The sensitivity of (18)F-DOPA PET for metastases of paraganglioma appears to be limited. PMID- 17873133 TI - Limitations of CT during PET/CT. AB - Our aim was to determine the diagnostic limitations of low-dose, unenhanced CT scans performed for anatomic reference and attenuation correction during PET/CT. METHODS: The Radiology Information System at our oncologic hospital was queried during the 9-mo period from July 2002 to April 2003 for patients with PET/CT scans and diagnostic enhanced CT within 2 wk of each other. One radiologist interpreted the CT portion of the PET/CT (CT(p)) unaware of the PET results and the associated enhanced diagnostic CT (CT(d)). A medical student compared this interpretation with the official report of the CT(d) and listed all discrepancies between reports. A separate radiologist compared CT(p) and CT(d) images and classified true discrepant findings as due to lack of intravenous contrast, arm position artifact, lack of enteric contrast, low milliamperage (mA), and quality of lung images. RESULTS: Among 100 patients, the most common malignancies were lymphoma (n = 37), cancer of the colorectum (n = 31), and esophageal cancer (n = 15). Among 194 true discrepancies in which findings were missed at CT(p), causes were as follows: (a) lack of intravenous contrast (128/194, 66%), (b) arm-down artifact (17/194, 9%), (c) quality of lung images (26/194, 13%), (d) lack of enteric contrast (15/194, 8%), and (e) low mA (8/194, 4%). Discrepancies were seen most commonly in detecting lymphadenopathy and visceral metastases. CONCLUSION: Most missed findings on the unenhanced CT portion of the PET/CT scans were due to technical factors that could be altered. Discrepant findings would have led to altered management in only 2 patients, suggesting a role for limited repeat imaging to reduce radiation and use of valuable resources. PMID- 17873134 TI - PET studies of d-methamphetamine pharmacokinetics in primates: comparison with l methamphetamine and ( --)-cocaine. AB - The methamphetamine molecule has a chiral center and exists as 2 enantiomers, d methamphetamine (the more active enantiomer) and l-methamphetamine (the less active enantiomer). d-Methamphetamine is associated with more intense stimulant effects and higher abuse liability. The objective of this study was to measure the pharmacokinetics of d-methamphetamine for comparison with both l methamphetamine and (-)-cocaine in the baboon brain and peripheral organs and to assess the saturability and pharmacologic specificity of binding. METHODS: d- and l-methamphetamine and (-)-cocaine were labeled with (11)C via alkylation of the norprecursors with (11)C-methyl iodide using literature methods. Six different baboons were studied in 11 PET sessions at which 2 radiotracer injections were administered 2-3 h apart to determine the distribution and kinetics of (11)C-d methamphetamine in brain and peripheral organs. Saturability and pharmacologic specificity were assessed using pretreatment with d-methamphetamine, methylphenidate, and tetrabenazine. (11)C-d-Methamphetamine pharmacokinetics were compared with (11)C-l-methamphetamine and (11)C-(-)-cocaine in both brain and peripheral organs in the same animal. RESULTS: (11)C-d- and l-methamphetamine both showed high uptake and widespread distribution in the brain. Pharmacokinetics did not differ between enantiomers, and the cerebellum peaked earlier and cleared more quickly than the striatum for both. (11)C-d Methamphetamine distribution volume ratio was not substantially affected by pretreatment with methamphetamine, methylphenidate, or tetrabenazine. Both enantiomers showed rapid, high uptake and clearance in the heart and lungs and slower uptake and clearance in the liver and kidneys. A comparison of (11)C-d methamphetamine and (11)C-(-)-cocaine showed that (11)C-d-methamphetamine peaked later in the brain than did (11)C-(-)-cocaine and cleared more slowly. The 2 drugs showed similar behavior in all peripheral organs examined except the kidneys and pancreas, which showed higher uptake for (11)C-d-methamphetamine. CONCLUSION: Brain pharmacokinetics did not differ between d-and l-methamphetamine and thus cannot account for the more intense stimulant effects of d methamphetamine. Lack of pharmacologic blockade by methamphetamine indicates that the PET image represents nonspecific binding, though the fact that methamphetamine is both a transporter substrate and an inhibitor may also play a role. A comparison of (11)C-d-methamphetamine and (11)C-(-)-cocaine in the same animal showed that the slower clearance of methamphetamine is likely to contribute to its previously reported longer-lasting stimulant effects relative to those of (-)-cocaine. High kidney uptake of d-methamphetamine or its labeled metabolites may account for the reported renal toxicity of d-methamphetamine in humans. PMID- 17873135 TI - 18F-FDG PET can replace conventional work-up in primary M staging of nonkeratinizing nasopharyngeal carcinoma. AB - Conventional work-up (CWU) with chest radiography, abdominal ultrasonography, and skeletal scintigraphy has limited value in M staging of nonkeratinizing nasopharyngeal carcinoma (NPC). Our aim was to evaluate whether (18)F-FDG PET could replace CWU by comparing their diagnostic efficacies. METHODS: Patients with histologically proven nonkeratinizing NPC and no prior treatment were prospectively enrolled. All study participants underwent CWU and (18)F-FDG PET for primary M staging. Distant metastasis was considered to be present if there was any reliable evidence identified within 1 y after diagnosis. The comparative diagnostic efficacies of (18)F-FDG PET, CWU, and the combination of (18)F-FDG PET and CWU (PET+CWU) were evaluated using the areas under the receiver-operating characteristic (ROC) curves. RESULTS: Sixty-one (20.3%) of 300 eligible patients were found to have distant metastases. On a patient-based analysis, (18)F-FDG PET was found to be more effective than CWU (P < 0.001), whereas it was equally effective with PET+CWU (P = 0.130). On region-based analyses, (18)F-FDG PET was more effective than skeletal scintigraphy and chest radiography for detecting bone metastases (P < 0.001) and chest metastases (P < 0.001), respectively. (18)F FDG PET and abdominal ultrasound were equally effective for detecting hepatic metastases (P = 0.127). On region-based analyses, the combination of (18)F-FDG PET and CWU did not yield any noticeable increase in diagnostic efficacy. CONCLUSION: (18)F-FDG PET can replace CWU in primary M staging of nonkeratinizing NPC. PMID- 17873136 TI - Processing of generator-produced 68Ga for medical application. AB - The (68)Ge/(68)Ga generator provides an excellent source of positron-emitting (68)Ga. However, newly available "ionic" (68)Ge/(68)Ga radionuclide generators are not necessarily optimized for the synthesis of (68)Ga-labeled radiopharmaceuticals. The eluates have rather large volumes, a high concentration of H(+) (pH of 1), a breakthrough of (68)Ge, increasing with time or frequency of use, and impurities such as stable Zn(II) generated by the decay of (68)Ga, Ti(IV) as a constituent of the column material, and Fe(III) as a general impurity. METHODS: We have developed an efficient route for the processing of generator-derived (68)Ga eluates, including the labeling and purification of biomolecules. Preconcentration and purification of the initial generator eluate are performed using a miniaturized column with organic cation-exchanger resin and hydrochloric acid/acetone eluent. The purified fraction was used for the labeling of nanomolar amounts of octreotide derivatives either in pure aqueous solution or in buffers. RESULTS: Using the generator post-eluate processing system, >97% of the initially eluated (68)Ga activity was obtained within 4 min as a 0.4-mL volume of a hydrochloric acid/acetone fraction. The initial amount of (68)Ge(IV) was decreased by a factor of 10(4), whereas initial amounts of Zn(II), Ti(IV), and Fe(III) were reduced by factors of 10(5), 10(2), and 10, respectively. The processed (68)Ga fraction was directly transferred to solutions containing labeling precursors-for example, DOTA-dPhe(1)-Tyr(3)-octreotide (DOTATOC) (DOTA = 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid). Labeling yields of >95% were achieved within 10 min. Overall yields reached 70% at 20 min after generator elution relative to the eluted (68)Ga activity, not corrected for decay. Specific activities of (68)Ga-DOTATOC were 50 MBq/nmol using a standard protocol, reaching 450 MBq/nmol under optimized conditions. CONCLUSION: Processing on a cation-exchanger in hydrochloric acid/acetone media represents an efficient strategy for the concentration and purification of generator-derived (68)Ga(III) eluates. The developed scheme guarantees high yields and safe preparation of injectable (68)Ga-labeled radiopharmaceuticals for routine application and is easy to automate. Thus, it is being successfully used in clinical environments and might contribute to a new direction for clinical PET, which could benefit significantly from the easy and safe availability of the radionuclide generator-derived metallic positron-emitter (68)Ga. PMID- 17873137 TI - Comparison of uptake of multiple clinical radiotracers into brown adipose tissue under cold-stimulated and nonstimulated conditions. AB - Our objective was to determine whether multiple clinically useful radiotracers accumulate in brown adipose tissue (BAT) and to assess their uptake in rats kept at room temperature or exposed to a cold environment. METHODS: The following radiotracers were injected intravenously into groups of 6 female Wistar rats: (201)Tl-chloride (TlCl), (123)I-metaiodobenzylguanidine (MIBG), (99m)Tc-sestamibi (MIBI), (18)F- or (3)H-FDG, (3)H-l-methionine, and (3)H-thymidine. BAT-stimulated animals were maintained at 4 degrees C for 4 h before tracer injection, whereas control animals were kept at approximately 22.5 degrees C. The animals were sacrificed at 20-60 min after tracer injection, and BAT, major organs, and blood were extracted, weighed, and measured for radioactivity. The localization of uncoupling protein-1, glucose transporter-1, and norepinephrine transporter was evaluated with immunohistochemical staining in both groups. RESULTS: We determined the percentage injected dose (%ID) per gram of each radiotracer in interscapular BAT, normalized to blood %ID/g. In control animals, this uptake ratio (+/-SD) was 8.44 +/- 3.39 for (201)TlCl, 9.77 +/- 6.06 for (123)I-MIBG, 37.30 +/- 14.42 for (99m)Tc-MIBI, 5.47 +/- 4.44 for (18)F- or (3)H-FDG, 1.93 +/- 0.87 for (3)H-l-methionine, and 1.22 +/- 0.74 for (3)H-thymidine. Compared with uptake at room temperature, uptake after exposure to cold increased 26.4-fold (P < 0.01) for (18)F- or (3)H-FDG and increased significantly (P < 0.05) for (201)Tl (2.04-fold), (123)I-MIBG (3.25-fold), and (3)H-l-methionine (3.11-fold). Immunohistochemical staining revealed increased glucose transporter-1 and norepinephrine transporter expression in BAT cell membranes and blood vessels after exposure to cold, whereas uncoupling protein-1 was expressed in the cytoplasm under both control and cold-stimulated conditions. CONCLUSION: BAT uptake of (18)F- or (3)H-FDG, (123)I-MIBG, and (3)H-l-methionine was significantly increased over the control state by exposure to cold. Increased uptake of (201)TlCl relative to blood in cold-stimulated BAT suggests that blood flow in BAT is increased by exposure to cold. The greater increased uptake with (18)F- or (3)H-FDG, (123)I-MIBG, and (3)H-l-methionine, and the immunohistostaining findings, suggest that other factors in addition to blood flow (e.g., increased metabolism, increased transport, or metabolic trapping of the tracers) are involved in cold-stimulated BAT activation. Knowledge that high uptake in BAT may possibly be observed on clinical scans using several radiotracers, especially after patients are exposed to the cold, may lead to more accurate interpretation of clinical studies. PMID- 17873138 TI - Chemotherapy response evaluation with 18F-FDG PET in patients with non-small cell lung cancer. AB - The aim of this prospective study was to evaluate the value of (18)F-FDG PET for the assessment of chemotherapy response in patients with non-small cell lung cancer. Furthermore, part of the objective of this study was to compare 2 methods to quantify changes in glucose metabolism. METHODS: In 51 patients, dynamic (18)F FDG PET was performed before and at 5-8 wk into treatment. Simplified methods to measure glucose metabolism (standardized uptake value [SUV]) and quantitative measures (metabolic rate of glucose [MR(Glu)]), derived from Patlak analysis, were evaluated. The overall survival and progression-free survival with respect to MR(Glu) and SUV were calculated using Kaplan-Meier estimates. Fractional changes in tumor glucose use were stratified by the median value and also the predefined EORTC (European Organization for Research and Treatment of Cancer) metabolic response criteria, and criteria applying cutoff levels similar to those of RECIST (Response Evaluation Criteria in Solid Tumors) were evaluated. RESULTS: When stratifying at the median value of DeltaMR(Glu) and DeltaSUV, the difference in overall survival (P = 0.017 for DeltaMR(Glu), P = 0.018 for DeltaSUV) and progression-free survival (P = 0.002 for DeltaMR(Glu), P = 0.0009 for DeltaSUV) was highly significant. When applying the predefined criteria for metabolic response, the cutoff levels as also used for size measurement (RECIST) showed significant differences for DeltaSUV between response categories in progression free survival (P = 0.0003) as well as overall survival (P = 0.027). CONCLUSION: The degree of chemotherapy-induced changes in tumor glucose metabolism as determined by (18)F-FDG PET is highly predictive for patient outcome, stratifying patients into groups with widely differing overall survival and progression-free survival probabilities. The use of (18)F-FDG PET for therapy monitoring seems clinically feasible, because simplified methods to measure tumor glucose use (SUV) are sufficiently reliable and can replace more complex, quantitative measures (MR(Glu)) in this patient population. PMID- 17873139 TI - MIRD continuing education: Bystander and low dose-rate effects: are these relevant to radionuclide therapy? AB - Bystander and low-dose-rate effects influence the dose-response relationship in a manner not predicted by current dosimetric methodologies. Radiation-induced bystander effects refer to biologic responses in cells that are not traversed by an ionizing radiation track and, thus, not subject to direct energy deposition; that is, the responses occur in nonirradiated cells. Low-dose-rate hypersensitivity effects have been documented as a reduction in the survival of cells irradiated at dose rates of 0.1-1.0 Gy/h, with total doses ranging from 1.5 to 5 Gy. For humans undergoing external radiotherapy, evidence of bystander events has been observed in the form of abscopal effects, wherein irradiation of one portion of the anatomy affects a portion outside the radiation field, whereas low-dose-rate hypersensitivity has not been described. In this report, the historical literature is briefly reviewed, key experiments are summarized, and current understanding of the factors thought to be involved in the bystander and low-dose-rate effects is conveyed. The mechanisms associated with these events are still being investigated, and questions remain on their impact in radionuclide therapy. Although current findings do not yet sufficiently justify changing traditional dose estimates used to predict the outcomes of radionuclide therapy, it is important to appreciate the potential importance of these effects and to begin revising methods to reflect the emerging empiric and mechanistic knowledge. PMID- 17873140 TI - Imaging of weak-source distributions in LSO-based small-animal PET scanners. AB - Lutetium oxyorthosilicate (LSO)- or lutetium-yttrium oxyorthosilicate (LYSO) based PET scanners have intrinsic radioactivity in the scintillator crystals due to the presence of (176)Lu, which decays by beta-emission followed by one or more prompt gamma-ray emissions. This leads to intrinsic true counts that can influence the image when scanning low levels of activity. An evaluation of the effects of this intrinsic activity for low levels of activity and different energy windows is performed on an LSO-based small-animal PET scanner. METHODS: Intrinsic count rate and sensitivity were measured for a range of lower-level discriminators (LLDs) ranging from 100 to 750 keV. The noise equivalent count rate (NECR) as a function of LLD for activity levels from 100 Bq to 100 kBq was estimated using a combination of measurement and previously published data for this scanner. Phantom imaging was performed using three (68)Ge sources of strength 55, 220, and 940 Bq and LLD levels of 250, 350, and 400 keV. The images were assessed using a contrast-to-noise ratio (CNR) analysis and by comparing the observed ratio of source activities to the true ratio value. RESULTS: The intrinsic true count rate is reduced from 940 counts per second (cps) for a 250- to 750-keV energy window to <2 cps for a 400- to 750-keV window. There is a corresponding 2-fold drop in sensitivity for detected true events for external positron sources for these 2 energy windows. The NECR versus LLD curves showed a highly peaked shape, with the optimum LLD being approximately 425 keV. The phantom image results were dominated by the intrinsic true counts when an energy window of 250-750 keV was used. The intrinsic true counts were almost completely removed by raising the LLD to 400 keV. The CNR for each of the sources was higher for the narrow energy window and the 55 Bq could be easily visualized in images acquired with LLD levels of 350 and 400 keV but not when the 250-keV LLD was used. Images acquired with an LLD of 400 keV and reconstructed with 2-dimensional filtered backprojection were the most quantitatively accurate. CONCLUSION: It is possible to visualize sources of <1 kBq in LSO-based animal PET systems by raising the LLD to 400 keV to exclude the majority of the counts due to the intrinsic activity present in the LSO. PMID- 17873141 TI - Evaluation of probable or possible dementia with lewy bodies using 123I-IMP brain perfusion SPECT, 123I-MIBG, and 99mTc-MIBI myocardial SPECT. AB - We evaluated the diagnostic usefulness of combination studies with a statistical mapping method in N-isopropyl-p-(123)I-iodoamphetamine ((123)I-IMP) brain perfusion SPECT, cardiac sympathetic nerve function by (123)I metaiodobenzylguanidine ((123)I-MIBG), and myocardial function by electrocardiographically gated (99m)Tc-sestamibi ((99m)Tc-MIBI) SPECT for patients with probable or possible dementia with Lewy bodies (DLB). METHODS: Twelve patients with probable DLB (7 male, 5 female; mean age +/- SD, 72.3 +/- 5.63 y; range, 65-82 y) and 9 patients with possible DLB (3 male, 6 female; mean age +/- SD, 73.1 +/- 9.23 y; range, 59-88 y) were enrolled in this study. (123)I IMP SPECT images were analyzed with 3-dimensional stereotactic surface projections (3D-SSP) and the severity of ischemia was classified objectively using quantitatively analytic and display software; stereotactic extraction estimation (SEE) methods were compared with a normal database. In addition, we evaluated (123)I-MIBG heart-to-mediastinum (H/M) uptake ratios. Moreover, we performed (99m)Tc-MIBI SPECT to evaluate myocardial perfusion and the left ventricular ejection fraction (LVEF) compared with a normal database. RESULTS: 3D SSP images of group comparison with healthy control subjects showed significantly decreased perfusion in the parietotemporal, occipital cortex, posterior cingulated, and precuneus regions in the probable DLB group but no significant reduction in the possible DLB group. Mean H/M ratios in the probable DLB group were significantly lower than those of the possible DLB group and the control group, respectively. Ten of 12 patients (83.3%) with probable DLB and 1 of 9 patients (11.1%) with possible DLB showed severe reduction in the bilateral occipital lobe and also a low (123)I-MIBG uptake. One patient (8.3%) with probable DLB and 2 patients (22.2%) with possible DLB showed no bilateral occipital hypoperfusion but showed low (123)I-MIBG uptake. One patient (8.3%) with probable DLB and 6 patients (66.7%) with possible DLB showed no occipital hypoperfusion and normal (123)I-MIBG uptake. (99m)Tc-MIBI gated SPECT did not indicate any wall motion abnormality in any subjects. CONCLUSION: These results suggest that combined examination of cerebral blood flow with 3D-SSP and SEE analysis, and cardiac sympathetic nerve function with (123)I-MIBG, would be a useful supporting diagnostic method in patients with DLB-particularly, in possible DLB and when cerebral blood flow does not indicate occipital hypoperfusion. PMID- 17873142 TI - Long-term nicorandil therapy improves cardiac sympathetic nerve activity after reperfusion therapy in patients with first acute myocardial infarction. AB - Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, reduces plasma norepinephrine concentration in patients with ischemic heart disease. However, long-term effects on cardiac sympathetic nerve activity (CSNA) as evaluated by (123)I-metaiodobenzylguanidine (MIBG) scintigraphy have not been determined for patients with acute myocardial infarction (AMI). METHODS: We studied 40 patients with their first AMI who were treated with intravenous nicorandil before and after primary coronary angioplasty. After suspension of the initial intravenous nicorandil treatment, 20 patients were randomized to receive oral nicorandil (15 mg/d) (group A) and the other 20 patients received a placebo (group B). All patients were also treated with an angiotensin-converting enzyme (ACE) inhibitor or beta-blockers. The delayed heart-to-mediastinum count ratio (H/M ratio), delayed total defect score (TDS), and washout rate (WR) were determined from (123)I-MIBG scintigraphy 3 wk and 6 mo after angioplasty. The left ventricular (LV) end-diastolic volume (EDV), LV end-systolic volume (ESV), and LV ejection fraction (EF) were determined by contrast left ventriculography, whereas plasma procollagen type III amino-terminal peptide (PIIINP) concentrations were also measured at the same time points. RESULTS: Three weeks after angioplasty, TDS, H/M ratios, WR, LVEDV, LVESV, and LVEF were similar in both groups. After 6 mo, all of these parameters had improved in both groups. However, the extent of change in TDS was -9 +/- 6 in group A and -5 +/- 6 in group B (P < 0.05), whereas that in the H/M ratio was 0.15 +/- 0.13 and 0.07 +/- 0.11 (P < 0.05) and that in the WR was -12% +/- 8% and -5% +/- 11% (P < 0.05). The extent of change in LVEDV, LVESV, and LVEF in group A tended to exceed that in group B, but these changes were not statistically significant. We found significant correlations between the percent change in PIIINP and that of TDS from baseline to 6 mo in group A (r = 0.456, P < 0.05). CONCLUSION: Long-term nicorandil therapy can be more beneficial for CSNA and LV remodeling than short term therapy in patients with AMI. PMID- 17873143 TI - Is unilateral posterior crossbite associated with leg length inequality? AB - It has been suggested that malocclusions may influence whole body posture, including leg length, but the current scientific evidence to support this statement is poor. The aim of the present study was to investigate a possible association between leg length inequality (LLI) and unilateral posterior crossbite. A survey was carried out in young adolescents recruited from three schools. The sample included 1,159 subjects (633 males and 526 females) with a mean age of 12.3 years (range 10.1-16.1 years), who underwent an orthodontic and orthopaedic examination performed independently by orthodontists and orthopaedists. The data were analysed by means of logistic regression analysis. One hundred and twenty subjects (10.3 per cent) were diagnosed as having LLI. A unilateral posterior crossbite was found in 142 of the 1,159 subjects (12.2 per cent). Logistic multiple regression analysis, controlling for potential confounding variables, failed to reveal a significant association between LLI and unilateral posterior crossbite (odds ratio = 1.0, confidence limits = 0.6-1.9). A unilateral posterior crossbite does not appear to be associated with LLI, at least in young adolescents. PMID- 17873144 TI - Use of the centroid method of occlusion for studying the vertical and horizontal relationship of the mandible and maxilla. AB - The aim of the present study was to verify whether the centroid method of occlusion for studying mandibular and maxillary growth enables accurate determination of vertical occlusal patterns (open and deep bite). Lateral cephalograms were obtained of Japanese adult females aged over 18 years of age with a Class II malocclusion (61 open bite and 47 deep bite), or a Class III type open bite (70 subjects) or deep bite (21 subjects) malocclusion. One-way analysis of variance followed by a Bonferroni's t-test was used to compare the results among these four groups. The Deltaabc area, which comprised the palatal, Ar-Gn, and A-B planes, was shown to be significantly larger in the open bite than in the deep bite group for both Class II and Class III malocclusion types (P < 0.01). There was no difference in the Deltaabc area between the Class II and Class III open bite groups or between the Class II and Class III deep bite groups. These findings suggest that the centroid method of occlusion is a versatile diagnostic technique that can accurately differentiate between vertical occlusal patterns of Class II and III types of malocclusion limited to Japanese adult females. The analytical method is also unaffected by gnathostatic differences according to Angle classification. PMID- 17873145 TI - The effect of ligation on the load deflection characteristics of nickel titanium orthodontic wire. AB - This study examined the effect of ligation on the load-deflection characteristics of nickel-titanium (NiTi) orthodontic wire. A modified three-point bending system was used for bending the NiTi round wire, which was inserted and ligated in the slots of three brackets, one of which was bonded to each of the three bender rods. Three different ligation methods, stainless steel ligature (SSL), slot lid (SL), and elastomeric ligature (EL), were employed, as well as a control with neither bracket nor ligation (NBL). The tests were repeated five times under each condition. Comparisons were made of load-deflection curve, load at maximum deflection of 2,000 microm, and load at a deflection of 1,500 microm during unloading. Analysis of Variance (ANOVA) and Dunnett's test were conducted to determine method difference (alpha = 0.05). The interaction between deflection and ligation was tested, using repeated-measures ANOVA (alpha = 0.05). The load values of the ligation groups were two to three times greater than the NBL group at a deflection of 1,500 microm during unloading: 4.37 N for EL, 3.90 N for SSL, 3.02 N for SL, and 1.49 N for NBL (P < 0.01). For the EL, a plateau region disappeared in the unloading curve. SL showed the smallest load. The ligation of the bracket wire may make NiTi wire exhibit a significantly heavier load than that traditionally expected. NiTi wire exhibited the majority of its true superelasticity with SL, whereas EL may act as a restraint on its superelasticity. PMID- 17873146 TI - Discolouration of orthodontic adhesives caused by food dyes and ultraviolet light. AB - Enamel discolouration after debonding of orthodontic attachments could occur because of irreversible penetration of resin tags into the enamel structure. Adhesives could discolour because of food dyes or ultraviolet irradiation. The aim of this study was to investigate the colour stability of adhesives during ultraviolet irradiation and exposure to food colourants. Four different adhesives were exposed in a Suntest CPS+ ageing device to a xenon lamp to simulate natural daylight (Transbond XT, Enlight, RelyX Unicem, and Meron Plus AC). Tomato ketchup, Coca Cola, and tea were chosen as the food colourants. After 72 hours of exposure, colour measurements were performed by means of a spectrophotometer according to the Commission Internationale de l'Eclairage L*a*b* system and colour changes (DeltaE*) were computed. Statistical differences were investigated using two-way analysis of variance (ANOVA) and Friedman test. Unsatisfactory colour stability after in vitro exposure to food colourants and ultraviolet light was observed for the conventional adhesive systems, Transbond XT and Enlight. RelyX Unicem showed the least colour change and the resin-reinforced glass ionomer cement (GIC), Meron Plus AC, the greatest colour change. The investigated adhesives seem to be susceptible to both internal and external discolouration. These in vitro findings indicate that the tested conventional adhesive systems reveal unsatisfactory colour stability which should be improved to avoid enamel discolouration. PMID- 17873147 TI - Reduced mandibular cast splints an alternative in Herbst therapy? A prospective multicentre study. AB - The aim of this study was to analyse anchorage loss with reduced, in comparison with total mandibular cast splints during Herbst treatment. Lateral head films of 32 Class II division 1 patients (15 females, 17 males) aged 13.0 years with reduced mandibular cast splints (RMS: second premolar to second premolar) and of 34 Class II division 1 patients (19 females, 15 males) aged 13.9 years with total mandibular cast splints (TMS: molar to molar) were analysed before (T1) and directly after (T2) Herbst treatment. Anchorage loss was assessed considering mandibular incisor proclination, changes of lower incisor edge position, and changes of occlusal plane inclination. To assess possible group differences, Student's t-tests were applied. The lower incisors proclined more in the RMS (11.8 degrees) than in the TMS (9.3 degrees) group. However, the amount of incisal edge advancement was less in the RMS (2.9 mm) than in the TMS (3.7 mm) group. The occlusal plane tilted insignificantly less in the RMS (5.7 degrees) than in the TMS (6.3 degrees) group. Reduced and total mandibular casted splint anchorage seemed to be similarly effective. Anchorage loss, measured by mandibular incisor proclination, was greater in the reduced anchorage group, whereas measured by lower incisor edge advancement, it was larger in the total anchorage group. Therefore, RMS can be recommended for Herbst treatment since they are less expensive than total splints. PMID- 17873148 TI - An in vitro comparative assessment of different enamel contaminants during bracket bonding. AB - In orthodontics, adhesive failures can occur because of saliva contamination during bonding. However, most in vitro studies concerning bond strength of saliva contaminated enamel disregard the influence of temperature changes in a wet environment. The aim of the present study was to compare the influence of saliva, blood and etching gel remnant contamination on shear bond strength (SBS) after thermocycling. After etching of extracted human third molars (n = 80), a conventional primer (Transbond XT) and a moisture-insensitive primer (Transbond MIP) were evaluated using the adhesive, Transbond XT, under dry conditions and after contamination with saliva, blood and etching gel remnants. To simulate temperature changes and the moisture of saliva in the oral cavity, all samples were thermocycled (6,000 x 5 degrees C/55 degrees C) in a mastication device before SBS testing. A Mann-Whitney U test was used to determine statistical differences. Under dry conditions Transbond XT and Transbond MIP showed no significant difference in SBS. However, clinically unacceptable (P = 0.005) bond strength was observed using Transbond XT after saliva and blood contamination. In wet conditions only Transbond MIP showed sufficient bond strength. If contamination during bonding is expected, a hydrophilic primer should be used. Under dry conditions hydrophilic or hydrophobic primers could be applied. Blood contamination seems to be a more serious problem for bond strength than saliva or etching gel contamination. PMID- 17873149 TI - Genetic structure and mating system of Manilkara huberi (Ducke) A. Chev., a heavily logged Amazonian timber species. AB - In this work, we report on the population genetic structure of the endangered tree species Manilkara huberi, an Amazonian tree species intensely exploited due to the high density and resistance of its wood. We investigated the patterns of spatial distribution, genetic structure, and mating system using 7 microsatellite loci and here discuss the consequences for conservation and management of the species. To examine the population genetic structure, 481 adult trees and 810 seedlings were sampled from an area of 200 ha from a natural population in FLONA Tapajos, PA, Brazil. We found relatively high and consistent inbreeding levels (intrapopulation fixation index [f] 0.175 and 0.240) and a significant spatial genetic structure up to a radius of approximately 300 m, most likely due to a limited seed and pollen flow. The multilocus (tm) population outcrossing rate was high (0.995), suggesting that the species is predominantly allogamous with a pollen flow restricted to 47 m. These results suggest that M. huberi is spatially structured, consistent with a model of isolation by distance. Fragmentation may therefore cause the loss of subpopulations, suggesting that management programs for production and conservation should include large areas. The genetic data also revealed that for ex situ conservation, seeds should be collected from more than 175 maternal trees, in order to keep an effective population size of 500. Furthermore, as the species is widely distributed across the Amazon Forest, samples should include several populations in order to represent the highest genetic diversity possible. These results provide a blueprint to guide the production and conservation management policies of this valuable timber species. PMID- 17873150 TI - The stability of inhibitory and working memory deficits in children and adolescents who are children of parents with schizophrenia. AB - Cognitive deficits are a central feature of schizophrenia and occur in first degree relatives of schizophrenic probands, even in the absence of psychotic symptoms. A number of cognitive domains have been implicated including measures of response inhibition and working memory. While the stability of cognitive deficits has been demonstrated in individuals with schizophrenia, stability of deficits has not been explored in first-degree relatives. This report focuses on 25 children (ages 6-15 years), all with at least one schizophrenic parent. The children were assessed twice, utilizing inhibitory and working memory tasks, with a mean 2.6 years between visits. Stop reaction time (a measure of motor inhibition) and performance on a counting span task (a measure of verbal working memory) were borderline to mildly impaired (compared with a typically developing comparison group) at both visits with similar effect sizes (stopping task time 1, effect size = 0.46, time 2 effect size = 0.50; counting span time 1 effect size = 0.53, time 2 effect size = 0.42). For these 2 tasks, individual age-adjusted scores also correlated across both time points (r = 0.41-0.76) suggesting that individual children maintained deficits across time. As etiologically driven strategies are developed for the cognitive deficits of schizophrenia, expansion of these treatments to relatives who share the cognitive but not the psychotic symptoms may be worth exploring. PMID- 17873151 TI - Cross-study validation and combined analysis of gene expression microarray data. AB - Investigations of transcript levels on a genomic scale using hybridization-based arrays have led to formidable advances in our understanding of the biology of many human illnesses. At the same time, these investigations have generated controversy because of the probabilistic nature of the conclusions and the surfacing of noticeable discrepancies between the results of studies addressing the same biological question. In this article, we present simple and effective data analysis and visualization tools for gauging the degree to which the findings of one study are reproduced by others and for integrating multiple studies in a single analysis. We describe these approaches in the context of studies of breast cancer and illustrate that it is possible to identify a substantial biologically relevant subset of the human genome within which hybridization results are reliable. The subset generally varies with the platforms used, the tissues studied, and the populations being sampled. Despite important differences, it is also possible to develop simple expression measures that allow comparison across platforms, studies, laboratories and populations. Important biological signals are often preserved or enhanced. Cross-study validation and combination of microarray results requires careful, but not overly complex, statistical thinking and can become a routine component of genomic analysis. PMID- 17873152 TI - Probability of detecting disease-associated single nucleotide polymorphisms in case-control genome-wide association studies. AB - Some case-control genome-wide association studies (CCGWASs) select promising single nucleotide polymorphisms (SNPs) by ranking corresponding p-values, rather than by applying the same p-value threshold to each SNP. For such a study, we define the detection probability (DP) for a specific disease-associated SNP as the probability that the SNP will be "T-selected," namely have one of the top T largest chi-square values (or smallest p-values) for trend tests of association. The corresponding proportion positive (PP) is the fraction of selected SNPs that are true disease-associated SNPs. We study DP and PP analytically and via simulations, both for fixed and for random effects models of genetic risk, that allow for heterogeneity in genetic risk. DP increases with genetic effect size and case-control sample size and decreases with the number of nondisease associated SNPs, mainly through the ratio of T to N, the total number of SNPs. We show that DP increases very slowly with T, and the increment in DP per unit increase in T declines rapidly with T. DP is also diminished if the number of true disease SNPs exceeds T. For a genetic odds ratio per minor disease allele of 1.2 or less, even a CCGWAS with 1000 cases and 1000 controls requires T to be impractically large to achieve an acceptable DP, leading to PP values so low as to make the study futile and misleading. We further calculate the sample size of the initial CCGWAS that is required to minimize the total cost of a research program that also includes follow-up studies to examine the T-selected SNPs. A large initial CCGWAS is desirable if genetic effects are small or if the cost of a follow-up study is large. PMID- 17873153 TI - The International Knee Documentation Committee Subjective Evaluation Form in a preadolescent population: pilot normative data. AB - BACKGROUND: The International Knee Documentation Committee Subjective Knee Evaluation Form is a knee-specific instrument composed of 18 questions. It is commonly used in adult and pediatric studies as a surgical outcome measure. Normative data exist for an adult population, but there have been no published normative results for younger subjects. PURPOSE: To compile and report pilot normative International Knee Documentation Committee Subjective Knee Evaluation Form scores in a preadolescent population. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: The International Knee Documentation Committee Subjective Knee Evaluation Form was administered to 146 seventh-grade students (aged 12-14 years) at 2 local schools. The form was administered in its original format. Demographic and descriptive results were compiled. RESULTS: One hundred twenty-five completed responses were eligible for analysis. The mean age was 13.2 years (SD, 0.5; range, 12.2-14.2 years); 15% of participants had a history of knee injury or pain. The mean International Knee Documentation Committee score for all respondents was 89.4 (SD, 10.5; 95% confidence interval, 87.6-91.3; range, 52-100). CONCLUSION: This study provides pilot normative data for mean International Knee Documentation Committee scores in a preadolescent population. The mean score in this younger cohort is consistent with normative data of adults age 35 years or younger. Although the International Knee Documentation Committee Subjective Knee Evaluation Form is often used in adolescent surgical studies, its validity in these populations remains to be established. Further work to establish the psychometric properties of the current form in younger age groups would be of significant benefit to clinicians. PMID- 17873154 TI - Cervical syrinx as a cause of shoulder pain in 2 athletes. PMID- 17873155 TI - Comparison of the split stacked versus the split achilles allograft for dual femoral tunnel posterior cruciate ligament reconstruction. AB - BACKGROUND: Cadaveric testing has shown that double-bundle reconstruction better replicates the native anatomy of the posterior cruciate ligament. With the current trend toward allograft Achilles posterior cruciate ligament reconstructions, the need to determine a graft configuration with the highest tensile and pull-out strength has become paramount. HYPOTHESIS: The split stacked Achilles allograft construct provides greater graft material to traverse the notch and provides increased load to failure at the tibial point of fixation compared with a standard monoblock Achilles allograft construct. STUDY DESIGN: Controlled laboratory study. METHODS: Eight matched pairs of Achilles allograft tendons were secured to 8 matched pairs of fresh-frozen human cadaveric tibiae. Group 1 consisted of single-block grafts (n = 8), and group 2 included the split stacked grafts (n = 8). The cross-sectional area of each graft's 2 collagenous bundles was measured with a micrometer. The graft constructs were pulled to ultimate failure at a rate of 50 mm/min on a materials testing machine. RESULTS: The mean cross-sectional area of the group 2 split stacked grafts (76.6 +/- 3.1 mm(2)) was significantly greater than that of the group 1 single-block grafts (48.2 +/- 3.0 mm(2); P =.00006). The maximum load to failure of the group 2 construct was significantly greater (1383 +/- 102 N) than that of the group 1 single-block configuration (1020 +/- 136 N; P =.01). CONCLUSION: These results indicate that the novel split stacked configuration of an Achilles tendon allograft provides a greater cross-sectional area of graft material across the joint as well as a significant increase in the overall load to failure strength compared with a standard monoblock Achilles allograft construct. CLINICAL RELEVANCE: The split stacked Achilles graft is an efficient method for using the entire allograft. With maintenance and use of all collagen fibers, the split stacked Achilles construct provides essentially 2 grafts in 1 while only using a single tibial tunnel. PMID- 17873156 TI - Diagnosis and management of lung cancer executive summary: ACCP evidence-based clinical practice guidelines (2nd Edition). PMID- 17873157 TI - Introduction: Diagnosis and management of lung cancer: ACCP evidence-based clinical practice guidelines (2nd Edition). PMID- 17873158 TI - Methodology for lung cancer evidence review and guideline development: ACCP evidence-based clinical practice guidelines (2nd Edition). AB - BACKGROUND: To assemble a geographically diverse panel of experts in the diagnosis and treatment of lung cancer, representative of multiple clinical specialties, with the intention of developing clinically relevant practice guidelines for chest medicine and primary care physicians, including recommendations covering the full spectrum of care of the patient with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). METHODS: The Duke University Center for Clinical Health Policy Research was selected to review and summarize the current evidence in the treatment of NSCLC. The BlueCross BlueShield Association Technology Evaluation Center was chosen and funded by the Agency for Healthcare Research and Quality to review and synthesize the current evidence on treatment of SCLC. Other chapters received existing guidelines, systematic reviews, and metaanalyses that were published since the first edition of these guidelines, as collected by the Duke University Evidence-based Practice Center. The writing committees for these chapters conducted searches for the primary articles and additional evidence in their topic area. The expert panel established clinical recommendations founded on the synthesis of this evidence. CONCLUSIONS: This section describes the approach used to develop the guidelines, including identifying, evaluating, and synthesizing the evidence, assessing the strength of evidence and grading the individual recommendations, and suggestions for implementation of the guidelines. PMID- 17873159 TI - Epidemiology of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). AB - BACKGROUND: The objective of this study was to summarize the published literature concerning the epidemiology of lung cancer. METHODS: A narrative review of published evidence was conducted, identifying and summarizing key reports that describe the occurrence of lung cancer in populations and factors that affect lung cancer risk. RESULTS: In the United States, lung cancer remains the leading cause of cancer death in both men and women, even though an extensive list of modifiable risk factors has long been identified. The predominant cause of lung cancer is exposure to tobacco smoke, with active smoking causing most cases but passive smoking also contributing to the lung cancer burden. CONCLUSIONS: The reductions in smoking prevalence in men that occurred in the late 1960s through the 1980s will continue to drive lung cancer mortality rates downward in men during the first portion of this century, but rates in women have not yet begun to decrease. Fortunately, exposures to major occupational respiratory carcinogens have largely been controlled, but the population is still exposed to environmental causes of lung cancer, including radon, the second leading cause of lung cancer death. PMID- 17873160 TI - Lung cancer chemoprevention: ACCP evidence-based clinical practice guidelines (2nd Edition). AB - BACKGROUND: Lung cancer is the most common cause of cancer death in the United States. Cigarette smoking is the main risk factor. Former smokers are at a substantially increased risk for lung cancer compared with lifetime never smokers. Chemoprevention is the use of specific agents to reverse, suppress, or prevent the process of carcinogenesis. This article reviews the major agents that have been studied for chemoprevention. METHODS: Articles of primary, secondary, and tertiary prevention trials were reviewed and summarized to obtain recommendations. RESULTS: None of the phase III trials with the agents beta carotene, retinol, 13-cis-retinoic acid, alpha-tocopherol, N-acetylcysteine, or acetylsalicylic acid has demonstrated beneficial, reproducible results. For facilitating the evaluation of promising agents and for lessening the need for a large sample size, extensive time commitment, and expense, focus is now turning toward the assessment of surrogate end point biomarkers for lung carcinogenesis. With the understanding of important cellular signaling pathways, various inhibitors that may prevent or reverse lung carcinogenesis are being developed. CONCLUSIONS: By integrating biological knowledge, more trials can be performed in a reasonable time frame. The future of lung cancer chemoprevention should entail the evaluation of single agents or combinations that target various pathways while working toward identification and validation of intermediate end points. PMID- 17873161 TI - Screening for lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). AB - BACKGROUND: Lung cancer typically exhibits symptoms only after the disease has spread, making cure unlikely. Because early-stage disease can be successfully treated, a screening technique that can detect lung cancer before it has spread might be useful in decreasing lung cancer mortality. OBJECTIVES: In this article, we review the evidence for and against screening for lung cancer with low-dose CT and offer recommendations regarding its usefulness for asymptomatic patients with no history of cancer. RESULTS: Studies of lung cancer screening with chest radiograph and sputum cytology have failed to demonstrate that screening lowers lung cancer mortality rates. Published studies of newer screening technologies such as low-dose CT and "biomarker" screening report primarily on lung cancer detection rates and do not present sufficient data to determine whether the newer technologies will benefit or harm. Although researchers are conducting randomized trials of low-dose CT, results will not be available for several years. In the meantime, cost-effectiveness analyses and studies of nodule growth are considering practical questions but producing inconsistent findings. CONCLUSIONS: For high-risk populations, no screening modality has been shown to alter mortality outcomes. We recommend that individuals undergo screening only when it is administered as a component of a well-designed clinical trial with appropriate human subjects' protections. PMID- 17873162 TI - Diagnostic surgical pathology in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). AB - OBJECTIVE: The objective of this study was to provide evidence-based background and recommendations for the development of American College of Chest Physicians guidelines for the diagnosis and management of lung cancer. METHODS: A systematic search of the medical and scientific literature using MEDLINE, MDCONSULT, UpToDate, Cochrane Library, NCCN guidelines, and NCI/NIH search engines was performed for the years 1990 to 2006 to identify evidence-based and consensus guidelines. The search was limited to literature on humans and articles in the English language. RESULTS: The pathologic assessment of lung cancers is based on a set of well-accepted findings, including histologic type, tumor size and location, involvement of visceral pleura, and extension to regional and distant lymph nodes and organs. Bronchial-based incipient neoplasia needs to be recognized both grossly and microscopically because these lesions may be multifocal and represent multistep carcinogenesis and may be amenable to therapy. Cytologic assessment of the individual with no symptoms is, as yet, of insufficient clinical benefit for screening of lung cancer. In challenging situations of pathologic differential diagnosis, additional studies may provide information that enables the separation of distinct tumor types. Pathobiological and molecular biological studies may yield prognostic and predictive information for clinical management and should be considered as part of protocol studies. Enhanced pathologic and molecular techniques may identify the presence of micrometastatic disease within lymph nodes; however, the clinical utility of these approaches is still unresolved. Intraoperative consultations have high diagnostic accuracy and may aid ongoing treatment and management decisions. CONCLUSIONS: Pathologic assessment is a crucial component for the diagnosis, management, and prognosis of lung cancer. Selective diagnostic techniques and decision analysis will increase diagnostic accuracy. Cytologic screening, molecular characterization of tumors, and micrometastatic analysis are potential but not yet proved modalities for the evaluation of lung cancers. PMID- 17873163 TI - Evidence for the treatment of patients with pulmonary nodules: when is it lung cancer?: ACCP evidence-based clinical practice guidelines (2nd edition). AB - BACKGROUND: The solitary pulmonary nodule (SPN) is a frequent incidental finding that may represent primary lung cancer or other malignant or benign lesions. The optimal management of the SPN remains unclear. METHODS: We conducted a systematic literature review to address the following questions: (1) the prevalence of SPN; (2) the prevalence of malignancy in nodules with varying characteristics (size, morphology, and type of opacity); (3) the relationships between growth rates, histology, and other nodule characteristics; and (4) the performance characteristics and complication rates of tests for SPN diagnosis. We searched MEDLINE and other databases and used previous systematic reviews and recent primary studies. RESULTS: Eight large trials of lung cancer screening showed that both the prevalence of at least one nodule (8 to 51%) and the prevalence of malignancy in patients with nodules (1.1 to 12%) varied considerably across studies. The prevalence of malignancy varied by size (0 to 1% for nodules < 5 mm, 6 to 28% for nodules 5 to 10 mm, and 64 to 82% for nodules > 20 mm). Data from six studies of patients with incidental or screening-detected nodules showed that the risk for malignancy was approximately 20 to 30% in nodules with smooth edges; in nodules with irregular, lobulated, or spiculated borders, the rate of malignancy was higher but varied across studies from 33 to 100%. Nodules that were pure ground-glass opacities were more likely to be malignant (59 to 73%) than solid nodules (7 to 9%). The sensitivity of positron emission tomography imaging for identifying a malignant SPN was consistently high (80 to 100%), whereas specificity was lower and more variable across studies (40 to 100%). Dynamic CT with nodule enhancement yielded the most promising sensitivity (sensitivity, 98 to 100%; specificity, 54 to 93%) among imaging tests. In studies of CT-guided needle biopsy, nondiagnostic results were seen approximately 20% of the time, but sensitivity and specificity were excellent when biopsy yielded a specific benign or malignant result. CONCLUSIONS: The prevalence of an SPN and the prevalence of malignancy in patients with an SPN vary widely across studies. The interpretation of these variable prevalence rates should take into consideration not only the nodule characteristics but also the population at risk. Modern imaging tests and CT-guided needle biopsy are highly sensitive for identifying a malignant SPN, but the specificity of imaging tests is variable and often poor. PMID- 17873164 TI - Evaluation of patients with pulmonary nodules: when is it lung cancer?: ACCP evidence-based clinical practice guidelines (2nd edition). AB - BACKGROUND: Pulmonary nodules are spherical radiographic opacities that measure up to 30 mm in diameter. Nodules are extremely common in clinical practice and challenging to manage, especially small, "subcentimeter" nodules. Identification of malignant nodules is important because they represent a potentially curable form of lung cancer. METHODS: We developed evidence-based clinical practice guidelines based on a systematic literature review and discussion with a large, multidisciplinary group of clinical experts and other stakeholders. RESULTS: We generated a list of 29 recommendations for managing the solitary pulmonary nodule (SPN) that measures at least 8 to 10 mm in diameter; small, subcentimeter nodules that measure < 8 mm to 10 mm in diameter; and multiple nodules when they are detected incidentally during evaluation of the SPN. Recommendations stress the value of risk factor assessment, the utility of imaging tests (especially old films), the need to weigh the risks and benefits of various management strategies (biopsy, surgery, and observation with serial imaging tests), and the importance of eliciting patient preferences. CONCLUSION: Patients with pulmonary nodules should be evaluated by estimation of the probability of malignancy, performance of imaging tests to characterize the lesion(s) better, evaluation of the risks associated with various management alternatives, and elicitation of patient preferences for treatment. PMID- 17873165 TI - Initial diagnosis of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). AB - BACKGROUND: Lung cancer is usually suspected in individuals who have an abnormal chest radiograph finding or have symptoms caused by either local or systemic effects of the tumor. The method of diagnosis of suspected lung cancer depends on the type of lung cancer (ie, small cell lung cancer [SCLC] or non-SCLC [NSCLC]), the size and location of the primary tumor, the presence of metastasis, and the overall clinical status of the patient. OBJECTIVES: To determine the test performance characteristics of various modalities for the diagnosis of suspected lung cancer. METHODS: To update previous recommendations on the initial diagnosis of lung cancer, a systematic search of MEDLINE, Healthstar, and Cochrane Library databases to July 2004, and print bibliographies was performed to identify studies comparing the results of sputum cytology, bronchoscopy, transthoracic needle aspiration (TTNA), or biopsy with histologic reference standard diagnoses among at least 50 patients with suspected lung cancer. Recommendations were developed by the writing committee, graded by a standardized method, and reviewed by all members of the lung cancer panel prior to approval by the Thoracic Oncology Network, Health and Science Policy Committee, and the Board of Regents of the American College of Chest Physician. RESULTS: Sputum cytology is an acceptable method of establishing the diagnosis of lung cancer with a pooled sensitivity rate of 0.66 and specificity rate of 0.99. However, the sensitivity of sputum cytology varies by location of the lung cancer. For central, endobronchial lesions, the overall sensitivity of flexible bronchoscopy (FB) for diagnosing lung cancer is 0.88. The diagnostic yield of bronchoscopy decreases for peripheral lesions. Peripheral lesions smaller or larger than 2 cm in diameter showed a sensitivity of 0.34 and 0.63, respectively. In recent years, endobronchial ultrasound (EBUS) has shown potential in increasing the diagnostic yield of FB while dealing with peripheral lesions without adding to the risk of the procedure. In appropriate situations, its use can be considered before moving on to more invasive tests. The pooled sensitivity for TTNA for the diagnosis of lung cancer is 0.90. A trend toward lower sensitivity was noted for lesions < 2 cm in diameter. The accuracy in differentiating between SCLC and NSCLC cytology for the various diagnostic modalities was 0.98, with individual studies ranging from 0.94 to 1.0. The average false-positive rate and FN rate were 0.09 and 0.02, respectively. CONCLUSIONS: The sensitivity of bronchoscopy is high for the detection of endobronchial disease and poor for peripheral lesions < 2 cm in diameter. Detection of the latter can be aided with the use of EBUS in the appropriate clinical setting. The sensitivity of TTNA is excellent for malignant disease. The distinction between SCLC and NSCLC by cytology appears to be accurate. PMID- 17873166 TI - Initial evaluation of the patient with lung cancer: symptoms, signs, laboratory tests, and paraneoplastic syndromes: ACCP evidenced-based clinical practice guidelines (2nd edition). AB - BACKGROUND: This chapter of the guidelines is intended to provide an evidence based assessment of the initial evaluation of patients recognized as having lung cancer and the recognition of paraneoplastic syndromes. METHODS: The current medical literature that is applicable to this issue was identified by a computerized search and was evaluated using standardized methods. Recommendations were framed using the approach described by the Health and Science Policy Committee of the American College of Chest Physicians. RESULTS: Patients with lung cancer usually present with multiple symptoms, both respiratory related and constitutional. There is usually a time delay between symptom recognition by the patient and the ultimate diagnosis of lung cancer by the physician. Whether this time delay impacts prognosis is unclear, but delivering timely and efficient care is an important component in its own right. Lung cancer may be accompanied by a variety of paraneoplastic syndromes. These syndromes may not necessarily preclude treatment with a curative intent. CONCLUSIONS: The initial evaluation of the patient with known or suspected lung cancer should include an assessment of symptoms, signs, and laboratory test results in a standardized manner as a screen for identifying those patients with paraneoplastic syndromes and a higher likelihood of metastatic disease. PMID- 17873167 TI - Physiologic evaluation of the patient with lung cancer being considered for resectional surgery: ACCP evidenced-based clinical practice guidelines (2nd edition). AB - BACKGROUND: This section of the guidelines is intended to provide an evidence based approach to the preoperative physiologic assessment of a patient being considered for surgical resection of lung cancer. METHODS: Current guidelines and medical literature applicable to this issue were identified by computerized search and evaluated using standardized methods. Recommendations were framed using the approach described by the Health and Science Policy Committee. RESULTS: The preoperative physiologic assessment should begin with a cardiovascular evaluation and spirometry to measure the FEV(1). If diffuse parenchymal lung disease is evident on radiographic studies or if there is dyspnea on exertion that is clinically out of proportion to the FEV(1), the diffusing capacity of the lung for carbon monoxide (Dlco) should also be measured. In patients with either an FEV(1) or Dlco < 80% predicted, the likely postoperative pulmonary reserve should be estimated by either the perfusion scan method for pneumonectomy or the anatomic method, based on counting the number of segments to be removed, for lobectomy. An estimated postoperative FEV(1) or Dlco < 40% predicted indicates an increased risk for perioperative complications, including death, from a standard lung cancer resection (lobectomy or greater removal of lung tissue). Cardiopulmonary exercise testing (CPET) to measure maximal oxygen consumption (Vo(2)max) should be performed to further define the perioperative risk of surgery; a Vo(2)max of < 15 mL/kg/min indicates an increased risk of perioperative complications. Alternative types of exercise testing, such as stair climbing, the shuttle walk, and the 6-min walk, should be considered if CPET is not available. Although often not performed in a standardized manner, patients who cannot climb one flight of stairs are expected to have a Vo(2)max of < 10 mL/kg/min. Data on the shuttle walk and 6-min walk are limited, but patients who cannot complete 25 shuttles on two occasions will likely have a Vo(2)max of < 10 mL/kg/min. Desaturation during an exercise test has not clearly been associated with an increased risk for perioperative complications. Lung volume reduction surgery (LVRS) improves survival in selected patients with severe emphysema. Accumulating experience suggests that patients with extremely poor lung function who are deemed inoperable by conventional criteria might tolerate combined LVRS and curative-intent resection of lung cancer with an acceptable mortality rate and good postoperative outcomes. Combining LVRS and lung cancer resection should be considered in patients with a cancer in an area of upper lobe emphysema, an FEV(1) of > 20% predicted, and a Dlco of > 20% predicted. CONCLUSIONS: A careful preoperative physiologic assessment will be useful to identify those patients who are at increased risk with standard lung cancer resection and to enable an informed decision by the patient about the appropriate therapeutic approach to treating their lung cancer. This preoperative risk assessment must be placed in the context that surgery for early-stage lung cancer is the most effective currently available treatment for this disease. PMID- 17873168 TI - Noninvasive staging of non-small cell lung cancer: ACCP evidenced-based clinical practice guidelines (2nd edition). AB - BACKGROUND: Correctly staging lung cancer is important because the treatment options and the prognosis differ significantly by stage. Several noninvasive imaging studies including chest CT scanning and positron emission tomography (PET) scanning are available. Understanding the test characteristics of these noninvasive staging studies is critical to decision making. METHODS: Test characteristics for the noninvasive staging studies were updated from the first iteration of the lung cancer guidelines using systematic searches of the MEDLINE, HealthStar, and Cochrane Library databases up to May 2006, including selected metaanalyses, practice guidelines, and reviews. Study designs and results are summarized in evidence tables. RESULTS: The pooled sensitivity and specificity of CT scanning for identifying mediastinal lymph node metastasis were 51% (95% confidence interval [CI], 47 to 54%) and 85% (95% CI, 84 to 88%), respectively, confirming that CT scanning has limited ability either to rule in or exclude mediastinal metastasis. For PET scanning, the pooled estimates of sensitivity and specificity for identifying mediastinal metastasis were 74% (95% CI, 69 to 79%) and 85% (95% CI, 82 to 88%), respectively. These findings demonstrate that PET scanning is more accurate than CT scanning. If the clinical evaluation in search of metastatic disease is negative, the likelihood of finding metastasis is low. CONCLUSIONS: CT scanning of the chest is useful in providing anatomic detail, but the accuracy of chest CT scanning in differentiating benign from malignant lymph nodes in the mediastinum is poor. PET scanning has much better sensitivity and specificity than chest CT scanning for staging lung cancer in the mediastinum, and distant metastatic disease can be detected by PET scanning. With either test, abnormal findings must be confirmed by tissue biopsy to ensure accurate staging. PMID- 17873169 TI - Invasive mediastinal staging of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). AB - BACKGROUND: The treatment of non-small cell lung cancer (NSCLC) is determined by accurate definition of the stage. If there are no distant metastases, the status of the mediastinal lymph nodes is critical. Although imaging studies can provide some guidance, in many situations invasive staging is necessary. Many different complementary techniques are available. METHODS: The current guidelines and medical literature that are applicable to this issue were identified by computerized search and were evaluated using standardized methods. Recommendations were framed using the approach described by the Health and Science Policy Committee of the American College of Chest Physicians. RESULTS: Performance characteristics of invasive staging interventions are defined. However, a direct comparison of these results is not warranted because the patients selected for these procedures have been different. It is crucial to define patient groups, and to define the need for an invasive test and selection of the best test based on this. CONCLUSIONS: In patients with extensive mediastinal infiltration, invasive staging is not needed. In patients with discrete node enlargement, staging by CT or positron emission tomography (PET) scanning is not sufficiently accurate. The sensitivity of various techniques is similar in this setting, although the false-negative (FN) rate of needle techniques is higher than that for mediastinoscopy. In patients with a stage II or a central tumor, invasive staging of the mediastinal nodes is necessary. Mediastinoscopy is generally preferable because of the higher FN rates of needle techniques in the setting of normal-sized lymph nodes. Patients with a peripheral clinical stage I NSCLC do not usually need invasive confirmation of mediastinal nodes unless a PET scan finding is positive in the nodes. The staging of patients with left upper lobe tumors should include an assessment of the aortopulmonary window lymph nodes. PMID- 17873170 TI - Bronchial intraepithelial neoplasia/early central airways lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). AB - BACKGROUND: An evidence-based approach is necessary for the localization and management of intraepithelial and microinvasive non-small cell lung cancer in the central airways. METHODS: Material appropriate to this topic was obtained by literature search of a computerized database. Recommendations were developed by the writing committee and then reviewed by the entire guidelines panel. The final recommendations were made by the Chair and were voted on by the entire committee. RESULTS: White light bronchoscopy has diagnostic limitations in the detection of microinvasive lesions. Autofluorescence bronchoscopy (AFB) is a technique that has been shown to be a sensitive method for detecting these lesions. In patients with moderate dysplasia or worse on sputum cytology and normal chest radiographic findings, bronchoscopy should be performed. If moderate/severe dysplasia or carcinoma in situ (CIS) is detected in the central airways, then bronchoscopic surveillance is recommended. The use of AFB is preferred if available. In a patient being considered for curative endobronchial therapy to treat microinvasive lesions, AFB is useful. A number of endobronchial techniques as therapeutic options are available for the management of CIS and can be recommended to patients with inoperable disease. In patients with operable disease, surgery remains the mainstay of treatment, although patients may be counseled about these techniques. CONCLUSIONS: AFB is a useful tool for the localization of microinvasive neoplasia. A number of endobronchial techniques available for the curative treatment can be considered first-line therapy in inoperable cases. For operable cases, the techniques may be considered and discussed with the patients. PMID- 17873171 TI - Treatment of non-small cell lung cancer stage I and stage II: ACCP evidence-based clinical practice guidelines (2nd edition). AB - BACKGROUND: The surgical treatment of stage I and II non-small cell lung cancer (NSCLC) continues to evolve in the areas of intraoperative lymph node staging (specifically the issue of lymph node dissection vs sampling), the role of sublobar resections instead of lobectomy for treatment of smaller tumors, and the use of video-assisted techniques to perform anatomic lobectomy. Adjuvant therapy (both chemotherapy and radiation therapy) and the use of larger fractions of radiotherapy delivered to a smaller area for nonoperative treatment of early stage NSCLC have shown promising results. METHODS: The panel selected the following areas for review based on clinical relevance and the amount and quality of data available for analysis: surgical approaches to resecting early stage NSCLC, methods of lymph node staging at the time of surgical resection, adjuvant chemotherapy in the treatment of early stage NSCLC, and the use of radiation therapy for primary treatment of early stage NSCLC as well as in the adjuvant setting. Recommendations by the multidisciplinary writing committee were based on literature review using established methods. RESULTS AND CONCLUSIONS: Surgical resection remains the treatment of choice for stage I and II NSCLC, although surgical methods continue to evolve. Adjuvant chemotherapy for patients with stage II, but not stage I, NSCLC is well established. Radiotherapy remains an important treatment for either cases of early stage NSCLC that are medically inoperable or patients who refuse surgery. PMID- 17873172 TI - Treatment of non-small cell lung cancer-stage IIIA: ACCP evidence-based clinical practice guidelines (2nd edition). AB - STUDY OBJECTIVES: Stage IIIA non-small cell lung cancer represents a relatively heterogeneous group of patients with metastatic disease to the ipsilateral mediastinal (N2) lymph nodes and also includes T3N1 patients. Presentations of disease range from apparently resectable tumors with occult microscopic nodal metastases to unresectable, bulky multistation nodal disease. This review explores the published clinical trials to make treatment recommendations in this controversial subset of lung cancer. DESIGN, SETTING, AND PARTICIPANTS: Systematic searches were made of MEDLINE, HealthStar, and Cochrane Library databases up to May 2006, focusing primarily on randomized trials, with inclusion of selected metaanalyses, practice guidelines, and reviews. Study designs and results are summarized in evidence tables. MEASUREMENT AND RESULTS: The evidence derived from the literature now appears to support routine adjuvant chemotherapy after complete resection of stage IIIA lung cancer encountered unexpectedly at surgery. However, using neoadjuvant therapy followed by surgery for known stage IIIA lung cancer as a routine therapeutic option is not supported by current published randomized trials. Combination chemoradiotherapy, especially delivered concurrently, is still the preferred treatment for prospectively recognized stage IIIA lung cancer with all degrees of mediastinal lymph node involvement. Current and future trials may modify these recommendations. CONCLUSIONS: Multimodality therapy of some type appears to be preferable in all subsets of stage IIIA patients. However, because of the relative lack of consistent randomized trial data in this subset, the following evidence-based treatment guidelines lack compelling evidence in most scenarios. PMID- 17873173 TI - Treatment of non-small cell lung cancer, stage IIIB: ACCP evidence-based clinical practice guidelines (2nd edition). AB - OBJECTIVE: To develop evidence-based guidelines on best available treatment options for patients with stage IIIB non-small cell lung cancer (NSCLC). METHODS: A review was conducted of published English-language (abstract or full text) phase II or phase III trials and guidelines from other organizations that address management of the various categories of stage IIIB disease. The literature search was provided by the Duke University Center for Clinical Health Policy Research and supplemented by any additional studies known by the authors. RESULTS: Surgery may be indicated for carefully selected patients with T4N0-1M0. Patients with N3 nodal involvement are not considered to be surgical candidates. For individuals with unresectable disease, good performance score, and minimal weight loss, treatment with combined chemoradiotherapy results in better survival than radiotherapy (RT) alone. Concurrent chemoradiotherapy seems to be associated with improved survival compared with sequential chemoradiotherapy. Multiple daily fractions of RT when combined with chemotherapy have not been shown to result in improved survival compared with standard once-daily RT combined with chemotherapy. The optimal chemotherapy agents and the number of cycles of treatment to combine with RT are uncertain. CONCLUSION: Prospective trials are needed to answer important questions, such as the role of induction therapy in patients with potentially resectable stage IIIB disease. Future trials are needed to answer the questions of optimal chemotherapy agents and radiation fractionation schedule. The role of targeted novel agents in combination with chemoradiotherapy is just starting to be investigated. PMID- 17873174 TI - Treatment of non-small cell lung cancer, stage IV: ACCP evidence-based clinical practice guidelines (2nd edition). AB - BACKGROUND: Stage IV non-small cell lung cancer (NSCLC) remains a treatable but incurable disease. METHODS: A MEDLINE search was performed to identify pertinent peer-reviewed articles that addressed the questions posed for this section. The writing committee developed and graded recommendations, which were subsequently approved by the American College of Chest Physicians. RESULTS: Platinum-based doublets remain the standard of care in patients with good performance status (PS); there is no evidence that the addition of a third cytotoxic agent improves survival. Likewise, with only one exception, the addition of a new targeted or biological agent to platinum-based doublets does not improve survival. The one exception is the addition of bevacizumab, an antiangiogenic agent, to carboplatin/paclitaxel in patients with stage IV disease and good PS. Patients for whom bevacizumab is recommended must also be selected on the basis of histology (nonsquamous), absence of brain metastases and hemoptysis, and no indication for therapeutic anticoagulation. In patients with stage IV NSCLC and PS of 2, chemotherapy is recommended, but the optimal approach has not been defined. Elderly patients, defined as >/= 70 years old, also derive benefit from chemotherapy. Most elderly patients should receive single-agent chemotherapy, but elderly patients with good PS and without significant comorbidities seem to derive a similar benefit from platinum-based doublets compared with their younger counterparts without a prohibitive difference in treatment toxicities. Because stage IV NSCLC is incurable, quality-of-life issues are important, and tools exist to monitor a patient's quality of life during therapy. Last, patients need to be informed of the implication of the diagnosis of stage IV NSCLC and be educated about treatment options that are available to them. CONCLUSIONS: Advances have been made in stage IV NSCLC, and the appropriate use of chemotherapy continues to evolve on the basis of well-designed clinical trials that address critical issues in this population. PMID- 17873175 TI - Special treatment issues in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). AB - BACKGROUND: This chapter of the guidelines addresses patients who have particular forms of non-small cell lung cancer that require special considerations. This includes patients with Pancoast tumors, T4N0,1M0 tumors, satellite nodules in the same lobe, synchronous and metachronous multiple primary lung cancers (MPLCs), solitary brain and adrenal metastases, and chest wall involvement. METHODS: The nature of these special clinical cases is such that in most cases, metaanalyses or large prospective studies of patients are not available. For ensuring that these guidelines were supported by the most current data available, publications that were appropriate to the topics covered in this chapter were obtained by performance of a literature search of the MEDLINE computerized database. When possible, we also referenced other consensus opinion statements. Recommendations were developed by the writing committee, graded by a standardized method (see "Methodology for Lung Cancer Evidence Review and Guideline Development" chapter), and reviewed by all members of the lung cancer panel before approval by the Thoracic Oncology NetWork, Health and Science Policy Committee, and the Board of Regents of the American College of Chest Physicians. RESULTS: In patients with a Pancoast tumor, a multimodality approach seems to be optimal, involving chemoradiotherapy and surgical resection, provided appropriate staging has been conducted. Patients with central T4 tumors that do not have mediastinal node involvement are uncommon. Such patients, however, seem to benefit from resection as part of the treatment as opposed to chemoradiotherapy alone when carefully staged and selected. Patients with a satellite lesion in the same lobe as the primary tumor have a good prognosis and require no modification of the approach to evaluation and treatment than what would be dictated by the primary tumor alone. However, it is difficult to know how best to treat patients with a focus of the same type of cancer in a different lobe. Although MPLCs do occur, the survival results after resection for either a synchronous presentation or a metachronous presentation with an interval of < 4 years between tumors are variable and generally poor, suggesting that many of these patients may have had a pulmonary metastasis rather than a second primary lung cancer. A thorough and careful evaluation of these patients is warranted to try to differentiate between patients with a metastasis and a second primary lung cancer, although criteria to distinguish them have not been defined. Selected patients with a solitary focus of metastatic disease in the brain or adrenal gland seem to benefit substantially from resection. This is particularly true in patients with a long disease-free interval. Finally, in patients with chest wall involvement, as long as tumors can be completely resected and there is absence of N2 nodal involvement, primary surgical treatment should be considered. CONCLUSIONS: Carefully selected patients may benefit from an aggressive surgical approach. PMID- 17873176 TI - Bronchioloalveolar lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). AB - OBJECTIVES: To review the current evidence on special issues relating to the diagnosis, imaging, prognosis, and treatment of bronchioloalveolar carcinoma (BAC). METHODS: This guideline focuses on aspects of BAC that are unique and ways in which BAC differs importantly from other forms of non-small cell lung cancer (NSCLC). The author reviewed published literature reporting on BAC using key words "histology," "CT scans," "fluorodeoxyglucose positron emission tomography scan," "sensitivity," "specificity," "surgical resection," "sublobar resection," and "epidermal growth factor receptor tyrosine kinase inhibitor" and selected references from published review articles. Also included was a review of the 1999 World Health Organization (WHO) revised classification system for lung tumors, which established a more restrictive definition of BAC to tumors with a pure lepidic spreading pattern and no evidence of stromal, vascular, or pleural invasion. RESULTS: With the notable exception of a lower likelihood of a positive positron emission tomography finding in the presence of BAC, staging, diagnosis, and treatment are the same as for other histologic subtypes of NSCLC, but additional treatment options that may prove to be equivalent, if not more effective, for more patients exist (eg, epidermal growth factor receptor tyrosine kinase inhibitor therapy, sublobar resection). CONCLUSIONS: BAC is a form of adenocarcinoma with unique clinical, radiologic, and epidemiologic features. The diagnosis of BAC should be reserved for tumors that meet the WHO criteria. Additional clinical trials are needed on this population of patients, using strict definitions and enrollment criteria to allow the results to be applied to appropriate patient populations. PMID- 17873177 TI - Evidence for management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). AB - PURPOSES: This systematic review addressed the following key questions on managing small cell lung cancer (SCLC): the sequence, timing, and dosing characteristics of primary thoracic radiotherapy (TRTx) for limited-stage disease; primary TRTx for extensive-stage disease; effect of prophylactic cranial irradiation (PCI); positron emission tomography (PET) for staging; treatment of mixed histology tumors; surgery; and second-line and subsequent-line treatment for relapsed/progressive disease. METHODS: The review methods were defined prospectively in a written protocol. We primarily sought randomized controlled trials that compared the interventions of interest. RESULTS: Robust evidence was lacking for all questions except PCI, for which a patient-level metaanalysis showed that PCI improves survival of SCLC patients who achieved complete response after primary therapy from 15.3 to 20.7% (p = 0.01). The case for concurrent over sequential radiation delivery rests largely on a single multicenter trial. Support for early concurrent therapy comes from one multicenter trial, but two other multicenter trials found no advantage. Metaanalysis did not find significant reductions in 2-year and 3-year mortality rates for early TRTx. Favorable results from a single-center trial on TRTx for extensive stage disease need replication in a multicenter setting. Relevant comparative studies were nonexistent for management of mixed histology disease and surgery for early limited SCLC. PET may be more sensitive in detecting extracranial disease than conventional staging modalities, but studies were of poor quality. CONCLUSIONS: PCI improves survival among those with a complete remission to primary therapy. A research agenda is needed to optimize the effectiveness of TRTx and its components. PMID- 17873178 TI - Management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). AB - PURPOSES: This guideline is for the management of patients with small cell lung cancer (SCLC) and is based on currently available information. As part of the guideline, an evidence-based review of the literature was commissioned that enables the reader to assess the evidence as we have attempted to put the clinical implications into perspective. METHODS: We conducted a comprehensive review of the available literature and the previous American College of Chest Physicians guidelines of SCLC. Controversial and less understood areas of the management of SCLC were then subject to an exhaustive review of the literature and detail analyses. Experts in evidence-based analyses compiled the accompanying systematic review titled "Evidence for Management of SCLC." The evidence was then assessed by a panel of experts to incorporate "clinical relevance." The resultant guidelines were then scored according to the grading system outlined by the American College of Chest Physicians grading system task force. RESULTS: SCLC accounts for 13 to 20% of all lung cancers. Highly smoking related and initially responsive to treatment, it leads to death rapidly in 2 to 4 months without treatment. SCLC is staged as limited-stage and extensive-stage disease. Limited stage disease is treated with curative intent with chemotherapy and radiation therapy, with approximately 20% of patients achieving a cure. For all patients with limited-stage disease, median survival is 16 to 22 months. Extensive-stage disease is primarily treated with chemotherapy with a high initial response rate of 60 to 70% but with a median survival of 10 months. All patients achieving a complete remission should be offered prophylactic cranial irradiation. Relapsed or refractory SCLC has a uniformly poor prognosis. CONCLUSION: In this section, evidence-based guidelines for the staging and treatment of SCLC are outlined. Limited-stage SCLC is treated with curative intent. Extensive-stage SCLC has high initial responses to chemotherapy but with an ultimately dismal prognosis with few survivors beyond 2 years. PMID- 17873179 TI - Complementary therapies and integrative oncology in lung cancer: ACCP evidence based clinical practice guidelines (2nd edition). AB - BACKGROUND: This chapter aims to differentiate between "alternative" therapies, often promoted falsely as viable options to mainstream lung cancer treatment, and complementary therapies, adjunctive, effective techniques that treat symptoms associated with cancer and its mainstream treatment, and to describe the evidence base for use of complementary therapies. METHODS AND DESIGN: A multidisciplinary panel of experts in oncology and integrative medicine evaluated the evidence for complementary (not alternative) therapies in the care of patients with lung cancer. Because few complementary modalities are geared to patients with only a single cancer diagnosis, symptom-control research conducted with other groups of patients with cancer was also included. Data on complementary therapies such as acupuncture, massage therapy, mind-body therapies, herbs and other botanicals, and exercise were evaluated. Recommendations were based on the strength of evidence and the risk-to-benefit ratio. RESULTS: Patients with lung and other poor-outlook cancers are particularly vulnerable to heavily promoted claims for unproved or disproved "alternatives." Inquiring about patients' use of these therapies should be routine because these practices may be harmful and can delay or impair treatment. Mind-body modalities and massage therapy can reduce anxiety, mood disturbance, and chronic pain. Acupuncture assists the control of pain and other side effects and helps reduce levels of pain medication required. Trials of acupuncture for chemotherapy-induced neuropathy and postthoracotomy pain show promising results. Herbal products and other dietary supplements should be evaluated for side effects and potential interactions with chemotherapy and other medications. CONCLUSIONS: Complementary therapies have an increasingly important role in the control of symptoms associated with cancer and cancer treatment. PMID- 17873180 TI - Follow-up and surveillance of the lung cancer patient following curative intent therapy: ACCP evidence-based clinical practice guideline (2nd edition). AB - BACKGROUND: To develop an evidence-based approach to follow-up of patients after curative intent therapy for lung cancer. METHODS: Guidelines on lung cancer diagnosis and management published between 2002 and December 2005 were identified by a systematic review of the literature, and supplemental material appropriate to this topic was obtained by literature search of a computerized database (Medline) and review of the reference lists of relevant articles. RESULTS: Adequate follow-up by the specialist responsible for the curative intent therapy should be ensured to manage complications related to the curative intent therapy and should last at least 3 to 6 months. In addition, a surveillance program should be considered to detect recurrences of the primary lung cancer and/or development of a new primary lung cancer early enough to allow potentially curative retreatment. A standard surveillance program for these patients, coordinated by a multidisciplinary tumor board and overseen by the physician who diagnosed and initiated therapy for the original lung cancer, is recommended based on periodic visits with chest imaging studies and counseling patients on symptom recognition. Smoking cessation and, if indicated, facilitation in participation in special programs is recommended for all patients following curative intent therapy for lung cancer. CONCLUSIONS: The current evidence favors follow-up of complications related to curative intent therapy, and a surveillance program at regular intervals with imaging and review of symptoms. Smoking cessation after curative intent therapy to prevent recurrence of lung cancer is strongly supported by the available evidence. PMID- 17873181 TI - Palliative care in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). AB - GOALS/OBJECTIVES: To review the scientific evidence on symptoms and specific complications that are associated with lung cancer, and the methods available to palliate those symptoms and complications. METHODS: MEDLINE literature review (through March 2006) for all studies published in the English language, including case series and case reports, since 1966 using the following medical subject heading terms: bone metastases; brain metastases; cough; dyspnea; electrocautery; hemoptysis; interventional bronchoscopy; laser; pain management; pleural effusions; spinal cord metastases; superior vena cava syndrome; and tracheoesophageal fistula. RESULTS: Pulmonary symptoms that may require palliation in patients who have lung cancer include those caused by the primary cancer itself (dyspnea, wheezing, cough, hemoptysis, chest pain), or locoregional metastases within the thorax (superior vena cava syndrome, tracheoesophageal fistula, pleural effusions, ribs, and pleura). Respiratory symptoms can also result from complications of lung cancer treatment or from comorbid conditions. Constitutional symptoms are common and require attention and care. Symptoms referable to distant extrathoracic metastases to bone, brain, spinal cord, and liver pose additional problems that require a specific response for optimal symptom control. There are excellent scientific data regarding the management of many of these issues, with lesser evidence from case series or expert opinion on other aspects of providing palliative care for lung cancer patients. CONCLUSIONS: Palliation of symptoms and complications in lung cancer patients is possible, and physicians who provide such care must be knowledgeable about these issues. PMID- 17873182 TI - Palliative care consultation, quality-of-life measurements, and bereavement for end-of-life care in patients with lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). AB - OBJECTIVE: To develop clinical practice guidelines for application of palliative care consultation, quality-of-life measurements, and appropriate bereavement activities for patients with lung cancer. METHODS: To review the pertinent medical literature on palliative care consultation, quality-of-life measurements, and bereavement for patients with lung cancer, developing multidisciplinary discussions with authorities in these areas, and evolving written guidelines for end-of-life care of these patients. RESULTS: Palliative care consultation has developed into a new specialty with credentialing of experts in this field based on extensive experience with patients in end-of-life circumstances including those with lung cancer. Bereavement studies of the physical and emotional morbidity of family members and caregivers before, during, and after the death of a cancer patient have supported truthful communication, consideration of psychological problems, effective palliative care, understanding of the patient's spiritual and cultural background, and sufficient forewarning of impending death. CONCLUSION: Multidisciplinary investigations and experiences, with emphasis on consultation and delivery of palliative care, timely use of quality-of-life measurements for morbidities of treatment modalities and prognosis, and an understanding of the multifaceted complexities of the bereavement process, have clarified additional responsibilities of the attending physician. PMID- 17873183 TI - Dr. Friedrich Wegener, the ACCP, and History. PMID- 17873184 TI - Transition from IV to subcutaneous prostacyclin: premature withdrawal? PMID- 17873185 TI - The tako-tsubo syndrome: an underappreciated, novel disease entity. PMID- 17873186 TI - New American College of Chest Physicians lung cancer guidelines: an important addition to the lung cancer guidelines armamentarium. PMID- 17873187 TI - Guidelines for guidelines: we've come a long way. PMID- 17873188 TI - Point: the ethics of unilateral "do not resuscitate" orders: the role of "informed assent". PMID- 17873189 TI - Counterpoint: is it ethical to order "do not resuscitate" without patient consent? PMID- 17873192 TI - Low value of routine chest radiographs in a mixed medical-surgical ICU. AB - OBJECTIVE: To determine the diagnostic efficacy (DE) and therapeutic efficacy (TE) of daily routine chest radiographs (CXRs), and to establish the impact of abandoning this CXR from daily practice on total CXR volume, ICU length of stay (LOS), readmission rate, and ICU mortality. DESIGN: Prospective controlled study in two parts. The first part comprised a 1-year period during which attending physicians were blinded for findings on daily routine CXRs and were only informed if something deemed important was seen by the radiologist (predefined major abnormalities) who reviewed all CXRs as usual. The second part comprised a half year period during which daily routine CXRs were replaced by clinically indicated CXR. SETTING: Mixed medical-surgical ICU of a teaching hospital. RESULTS: Data on 1,780 daily routine CXRs in 559 hospital admissions were collected. DE of daily routine CXRs was 4.4%. The most frequent unexpected major abnormalities were new or progressive infiltrates (1.8%) and oropharyngeal tube malposition (0.7%). TE of daily routine CXRs was 1.9%. The most frequent intervention was oropharyngeal tube adjustment (0.6%). No relation was found for DE or TE and hospital admission type or intubation and mechanical ventilation. In the second study part, 433 CXRs were obtained in 274 admissions. Abandoning daily routine CXRs did not affect clinically indicated CXRs orders, or ICU LOS, readmission rate, and mortality. A total CXR volume reduction of 35% (which equaled 9,900 per bed per year [US dollars]) was observed after abandoning daily routine CXRs. CONCLUSION: Diagnostic and therapeutic value of the daily routine CXR is low. Daily routine CXRs can be safely abandoned in the ICU. PMID- 17873193 TI - Nonpulmonary organ dysfunction and its impact on outcome in patients with acute respiratory failure. AB - PURPOSES: This study aimed to define the prevalence, severity, and progression of nonpulmonary organ dysfunction, and its impact on outcome in patients with acute respiratory failure (ARF) at a respiratory ICU of a tertiary referral hospital in northern India. METHODS: Daily patient data were collected on 711 adult patients with ARF to calculate component and total nonpulmonary sequential organ failure assessment (SOFA) scores. Hospital survival was the main outcome measure. Multiple logistic regression modeling was conducted to assess contribution of incremental dysfunction of various nonpulmonary organ systems to mortality. Kaplan-Meier curves were drawn to assess temporal trends in survival, and group comparisons were based on log-rank test. Cox proportional hazard modeling was performed to define hazards of earlier mortality. Discrimination was evaluated using receiver operating characteristic (ROC) curves. RESULTS: Four hundred seventy-five patients (66.8%) had one or more nonpulmonary organ dysfunctions at hospital admission. The overall hospital mortality rate was 33.9%. Hospital survival rates and median survival declined steadily as the number of organs involved increased. Admission, maximum, and DeltaSOFA scores were significantly higher in nonsurvivors. Increasing baseline cardiovascular and neurologic SOFA scores, and corresponding DeltaSOFA scores, were associated with progressively higher odds of hospital mortality, as well as increasing hazard for earlier mortality after adjustment for etiology of respiratory failure. Maximum nonpulmonary SOFA score was the best discriminator in predicting mortality (area under ROC curve, 0.767). CONCLUSION: Baseline and new-onset nonpulmonary organ dysfunction significantly influences hospital survival in patients with ARF. PMID- 17873194 TI - Pulmonary hypertension in idiopathic pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) is an untreatable diffuse parenchymal lung disease with a median survival of < 3 years. Pulmonary hypertension (PH) is frequently seen in patients with IPF and is commonly attributed to hypoxic vasoconstriction and capillary destruction. Pathology findings include endothelial proliferation and medial hypertrophy that exceed those expected in the setting of hypoxia. Noninvasive evaluation has limited sensitivity and specificity for the diagnosis of PH in IPF; therefore, right-heart catheterization remains the "gold standard" diagnostic test. PH in patients with IPF is associated with decreased exercise capacity and worse survival. Given the grave consequences of this condition, treatment of PH could improve functional outcomes and survival. However, possible treatments such as long-term supplemental oxygen and targeted vascular therapy are either unstudied or remain unproven. PMID- 17873195 TI - Regulatory T cells in allergy and asthma. AB - Allergic diseases including asthma have risen considerably in prevalence in the last 50 years. A concomitant rise in autoimmune disease suggests a defect in immunoregulation, rather than a reduction in T-helper type 1 immunity. Immune responses to innocuous environmental antigens in health are characterized by dominant regulation through the production of interleukin-10 and transforming growth factor-beta. Recent studies suggest that diverse populations of regulatory T cells (Treg) play an important role in regulating T-helper type 2 (Th2) responses to allergens, maintaining functional tolerance. Regulatory responses appear to be compromised in allergic individuals but may be reconstituted to some extent with specific allergen immunotherapy. In experimental models, Treg can suppress Th2 responses to allergen, airway eosinophilia, mucous hypersecretion, and airway hyperresponsiveness. Further studies are required to precisely define the mechanisms of development and action of these cells, and to identify and evaluate novel targets for the treatment of allergic diseases. PMID- 17873196 TI - A systematic review of population-based studies of infective endocarditis. AB - BACKGROUND: We sought to summarize and critically appraise the literature on the epidemiology of infective endocarditis (IE) in the general population. METHODS: We retrieved population-based IE surveys by searching MEDLINE and EMBASE. Two reviewers independently extracted relevant data. We performed a metaregression to determine if temporal trends of IE characteristics exist. RESULTS: Fifteen population-based investigations with 2,371 IE cases from seven countries (Denmark, France, Italy, the Netherlands, Sweden, United Kingdom, and United States) from 1969 to 2000 were eligible. Different case definitions and procedures were used to capture all IE cases, including census of existing diagnoses, record-linkage system, and direct contact survey. In the unadjusted regression, there was a decline in the proportion of IE patients with underlying rheumatic heart disease (RHD; 12%; 95% confidence interval [CI], - 21 to - 3%; p = 0.01) and an increase in the proportion of patients undergoing valve surgery (9%; 95% CI, 3 to 16%) per decade. After adjusting for country, the decline in IE cases with underlying RHD became nonsignificant, but the proportions of IE patients undergoing valve surgery increased 7% per decade (95% CI, - 4 to 14%; p = 0.06), and those with underlying prosthetic valve increased 7% per decade (95% CI, - 1 to 16%; p = 0.07). There were no significant temporal trends in the causative organisms. CONCLUSION: Evidence from well-planned, representative IE epidemiologic surveys is scarce in many countries. Available studies suggest a changing distribution of underlying valvular heart disease in patients with IE and an increase in its surgical treatment. PMID- 17873197 TI - Malignant pleural effusions: management options with consideration of coding, billing, and a decision approach. AB - Malignant pleural effusions (MPEs) are a troublesome and debilitating complication of advanced malignancies, with > 150,000 cases in the United States each year. The standard management approach begins with a diagnostic and/or therapeutic thoracentesis. Should the MPE recur, a more definitive management strategy is often undertaken with several approaches available to the chest physician or surgeon. These options include repeat thoracentesis, tube thoracostomy with chemical pleurodesis, placement of an indwelling cuffed, tunneled pleural catheter with or without pleurodesis, or medical pleuroscopy or video-assisted thoracoscopic surgery with pleurodesis. Each approach has unique advantages, disadvantages, and likelihood of successful symptom relief and pleurodesis. This article will provide a general review of MPE management strategies including information concerning coding, billing, documentation, and a decision approach among these various methods. PMID- 17873198 TI - Pulmonary toxicity associated with erlotinib. AB - Interstitial lung disease (ILD) related to therapy with the drug gefitinib has been well reported. The adverse pulmonary effects of erlotinib are less well known. We report a case of fatal pulmonary toxicity in a patient with advanced non-small cell lung cancer who received erlotinib. He had been found to have pathologic findings of usual interstitial pneumonia (UIP) on the resected lung cancer specimen prior to receiving erlotinib. This case and other published evidence should alert physicians to the possibility of fatal erlotinib-induced ILD. Similar to reports in patients receiving gefitinib, those with pathologic findings of UIP on resected lung specimens or known pulmonary fibrosis may be at particular risk for erlotinib pulmonary toxicity. PMID- 17873199 TI - Pneumothorax and pregnancy. AB - BACKGROUND: Though more common in male patients, primary spontaneous pneumothorax might be expected to occur reasonably often in female patients of child-bearing age. However, < 50 cases of pneumothorax in pregnancy have been previously reported. Special risks are posed for both the mother and the fetus in this situation. Previous management strategies have varied widely, without describing the more modern and less invasive techniques, and existing pneumothorax guidelines do not incorporate this difficult scenario. METHODS: A retrospective search of our database of 250 spontaneous pneumothorax patients over a 10-year period, in a stable local population of 500,000 patients, identified five cases of pneumothorax occurring in pregnancy. We report our experience, the largest series yet described, review the medical literature, and make management recommendations. RESULTS: We found favorable outcomes for both mothers and infants in our series, with modern techniques such as simple aspiration, elective assisted delivery at or near term with regional anesthesia, and video-assisted thoracoscopic surgery. CONCLUSIONS: Future guidelines on the management of pneumothorax should consider the inclusion of advice on the problems of pregnancy, based on previous published experience, and utilizing the modern and less invasive techniques. Such advice would inform and support those specialists involved in managing a potentially hazardous situation to the benefit of both mother and child. PMID- 17873200 TI - Discontinuing mechanical ventilatory support. AB - The ventilator discontinuation process is a critical component of ICU care. Ongoing ventilator dependency is caused by both disease factors (eg, respiratory, cardiac, metabolic, and neuromuscular) and clinician management factors (eg, failing to recognize discontinuation potential and inappropriate ventilator settings/management). A multispecialty evidence-based task force has recommended a series of guidelines that begins with a daily ventilator weaning screen focusing on disease stability/recovery, gas exchange, hemodynamics, and respiratory drive that should be done on every patient receiving mechanical ventilatory support. In those passing this screen, a spontaneous breathing trial (SBT) should be performed. The decision to remove the artificial airway in those patients successfully passing an SBT requires further assessment of the patient's ability to protect the airway. Managing the patient who fails the SBT is one of the biggest challenges facing ICU clinicians. In general, stable, comfortable modes of assisted/supported ventilatory support should be provided between the daily weaning screen/SBT. New evidence suggests that early tracheostomy placement may facilitate the ventilator withdrawal process in those patients requiring prolonged ventilatory support. PMID- 17873201 TI - Positive airway pressure treatment for obstructive sleep apnea. AB - Positive airway pressure (PAP) is the treatment of choice for patients with moderate-to-severe obstructive sleep apnea (OSA). Randomized controlled trials have demonstrated that PAP can effectively reduce the apnea-hypopnea index and improve subjective and objective sleepiness. Some studies have also demonstrated benefits in sleep quality and quality of life for both the patient and bed partner. Observational studies have shown a reduction in the risk of cardiovascular events in OSA patients treated with PAP compared to untreated patients. Since continuous PAP (CPAP) treatment of OSA was described, additional modes of pressure delivery have been developed (bilevel PAP, autoadjusting PAP, flexible PAP). While none of the variants of PAP improves adherence in unselected patients compared to CPAP, individual patients may respond to a change in pressure mode. Attended PAP titration remains the standard of practice for selecting a treatment pressure. However, use of autotitrating PAP devices in the unattended setting can provide an effective titration alternative with careful patient selection and review of titration results. More choices of mask interface are now available to improve comfort and intervene for mask or mouth leaks. However, despite the increase in PAP treatment options, lack of acceptance and inadequate adherence to PAP therapy remain the major causes of treatment failure. Some studies suggest that heated humidification can improve PAP adherence, especially in patients with nasal congestion or dryness. A systematic approach to PAP treatment including education, objective adherence monitoring, early intervention for side effects, and telephone and clinic support is essential to optimize adherence. PMID- 17873202 TI - How to choose the right journal for your manuscript. PMID- 17873203 TI - A 22-year-old woman with fever, jaw pain, and shock. PMID- 17873204 TI - A 33-year-old man with pharyngitis, transient rash, and multiorgan system failure. PMID- 17873205 TI - A 21-year-old man with hemoglobin SC disease and acute shortness of breath with left upper abdominal pain. PMID- 17873206 TI - A 31-year-old man with hemoptysis at high altitude and abnormal hepatic biochemistry tests. PMID- 17873207 TI - Corticosteroids in ARDS: a counterpoint. PMID- 17873208 TI - Steroids in Early ARDS. PMID- 17873209 TI - Low-dose steroids in ARDS. PMID- 17873210 TI - Steroids for ARDS: still an open issue. PMID- 17873211 TI - Methylprednisolone infusion in early severe ARDS. PMID- 17873212 TI - Methylprednisolone infusion in early severe ARDS: it is pretty, but is it art? PMID- 17873214 TI - Vancomycin dosing for methicillin-resistant staphylococcus aureus nosocomial pneumonia. PMID- 17873215 TI - Appropriate pharmacokinetic index for outcome in Staphylococcus aureus pneumonia. PMID- 17873216 TI - Methicillin-resistant Staphylococcus aureus pneumonia treatment: do not confuse pharmacokinetics and pharmacodynamics. PMID- 17873217 TI - Preventing the leading cause of death in young people in Europe. PMID- 17873218 TI - Community pharmacy and public health in Great Britain, 1936 to 2006: how a phoenix rose from the ashes. AB - The pharmacy profession in Great Britain has identified public health as a key area for future development; at the same time the government has been keen to make full use of pharmacists in pursuing its public health goals. To date, pharmacy has focused on microlevel activities such as health promotion, medicines management and prescribing advice, rather than on wider public health issues such as health inequalities. The role in health promotion has its origins in the traditional advisory role of the pharmacist, which largely died out following the establishment of the National Health Service in 1948, and was resurrected only following ministerial intervention in 1981. This article traces the origins of the pharmacist's role in public health, illustrating both shifting definitions of public health and changes in pharmacy practice. It describes how the profession was able to re-establish its advisory role and to develop it into a wider contribution to public health, indicating that this process came about as a result of convergence between a professional imperative to develop its role, on the one hand, and state recognition of the need to draw a broader range of health professionals and lay people into public health activities, on the other. Convergence required the securing of government support, confirmed in policy documents; the recognition by pharmacy's professional body that embracing public health is a desirable activity; incentives for community pharmacists to carry out such activities; and support from the wider public health community. This article describes how each of these was achieved. PMID- 17873219 TI - Income inequality measures. AB - The Gini coefficient has been the most popular method for operationalising income inequality in the public health literature. However, a number of alternative methods exist, and they offer researchers the means to develop a more nuanced understanding of the distribution of income. Income inequality measures such as the generalised entropy index and the Atkinson index offer the ability to examine the effects of inequalities in different areas of the income spectrum, enabling more meaningful quantitative assessments of qualitatively different inequalities. This glossary provides a conceptual introduction to these and other income inequality measures. PMID- 17873221 TI - "Profits before people"? A systematic review of the health and safety impacts of privatising public utilities and industries in developed countries. AB - Debates on government privatisation policies have often focused on the alleged effects of privatisation on health and safety. A systematic review (through Quality of Reporting of Meta-analysis) of the effects of privatising industries and utilities on the health (including injuries) of employees and the public was conducted. The data sources were electronic databases (medical, social science and economic), bibliographies and expert contacts. Experimental and quasi experimental studies were sought, dating from 1945, from any Organisation for Economic Cooperation and Development member country (in any language) that evaluated the health outcomes of such interventions. Eleven highly heterogeneous studies that evaluated the health impacts of privatisation of building, water, paper, cement, bus, rail, mining, electric and gas companies were identified. The most robust study found increases in the measures of stress-related ill health among employees after a privatisation intervention involving company downsizing. No robust evidence was found to link privatisation with increased injury rates for employees or customers. In conclusion, public debates on the health and safety implications of privatisation have a poor empirical base, which policy makers and researchers need to address. Some evidence suggests that adverse health outcomes could result from redundancies associated with privatisation. PMID- 17873220 TI - Toward the next generation of research into small area effects on health: a synthesis of multilevel investigations published since July 1998. AB - To map out area effects on health research, this study had the following aims: (1) to inventory multilevel investigations of area effects on self rated health, cardiovascular diseases and risk factors, and mortality among adults; (2) to describe and critically discuss methodological approaches employed and results observed; and (3) to formulate selected recommendations for advancing the study of area effects on health. Overall, 86 studies were inventoried. Although several innovative methodological approaches and analytical designs were found, small areas are most often operationalised using administrative and statistical spatial units. Most studies used indicators of area socioeconomic status derived from censuses, and few provided information on the validity and reliability of measures of exposures. A consistent finding was that a significant portion of the variation in health is associated with area context independently of individual characteristics. Area effects on health, although significant in most studies, often depend on the health outcome studied, the measure of area exposure used, and the spatial scale at which associations are examined. PMID- 17873222 TI - Healthy lifestyle choices: could sense of coherence aid health promotion? AB - BACKGROUND: A research framework based on the personal characteristic defined by a sense of coherence (SOC) focuses on the effective use of resources to maintain good health. OBJECTIVES: To test the hypothesis that individual differences in SOC are associated with healthier lifestyle choices independently of social class and education. DESIGN AND SETTING: Cross sectional. Population based cohort study recruited through 35 general practice registers. Reported dietary intakes of alcohol, fruit and vegetables, fibre, saturated fat, non-discretionary salt (sodium), and total sugars were assessed by food frequency questionnaire. Current cigarette smoking, physical inactivity, and SOC were assessed through questionnaires. PARTICIPANTS: 7,863 men and 10,424 women. Residents of Norfolk (UK). RESULTS: Compared with participants with the weakest SOC, those with the strongest were 28% less likely to be current smokers (odds ratio 0.72 (95% confidence interval (CI), 0.58 to 0.89)), 36% less likely to be physically inactive (0.64 (0.55 to 0.75)), and reportedly consumed on average 63 g/day more fruit and vegetables (95% CI, 46 to 80), and 1.2 g/day more fibre (0.8 to 1.6). These associations were independent of age, sex, social class, and education. For physical inactivity and consumption of fruit, vegetables, and fibre, these differences exceeded those observed between the extremes of social class and education. CONCLUSIONS: Individual differences in SOC are associated with healthy lifestyle choices independently of social class and education, and may therefore aid the design of future health promotion interventions. PMID- 17873223 TI - Evidence-based policy on road safety: the effect of the demerit points system on seat belt use and health outcomes. AB - OBJECTIVE: To assess the effect of a demerit points system, introduced in Italy in July 2003, on the prevalence of seat belt use (intermediate outcome) and the number of road traffic deaths and injuries (health outcomes). DESIGN: Pre- and post-intervention regional observational study for seat belt investigation (April 2003, October 2004); national time-series analysis of road traffic deaths and injuries between 1999 and 2004 for health outcomes. SETTING: Veneto region, Italy. PARTICIPANTS: 19,551 drivers, 19,057 front passengers and 8,123 rear passengers estimated to be aged over 11 years were included in the investigation into seat belt use. 38,154 fatalities and 1,938,550 injured subjects were examined for the time-series analysis. INTERVENTIONS: Demerit points system. MAIN OUTCOME MEASURES: The proportions of drivers and front and rear passengers observed to be using seat belts before and after the intervention; estimates of lives and injuries saved through the implementation of a penalty points system. RESULTS: The demerit points system was followed by an increase in observed seat belt use of 51.8% (95% confidence interval 48.7% to 54.9%) among drivers, of 42.3% (95% confidence interval 39.2% to 45.5%) among front passengers and of 120.7% (95% confidence interval 99.4% to 144.3%) among rear passengers. It is estimated that 1,545 (95% confidence interval 1387 to 1703; p<0.0001) deaths and 91,772 (95% confidence interval 67,762 to 115,783; p<0.0001) injuries were prevented in the 18 months after the introduction of the legislation, i.e. an 18% reduction (1545/8570) in fatalities and a 19% reduction (91,772/473,048) in injuries. CONCLUSIONS: The demerit points system is effective both in encouraging drivers and passengers to adhere to the law and in terms of health outcomes, substantially contributing to road safety. PMID- 17873224 TI - Contribution of neighbourhood socioeconomic status and physical activity resources to physical activity among women. AB - INTRODUCTION: Residence in a deprived neighbourhood is associated with lower rates of physical activity. Little is known about the manifestation of deprivation that mediates this relationship. This study aimed to investigate whether access to physical activity resources mediated the relationship between neighbourhood socioeconomic status and physical activity among women. METHOD: Individual data from women participating in the Stanford Heart Disease Prevention Program (1979-90) were linked to census and archival data from existing records. Multilevel regression models were examined for energy expenditure and moderate and vigorous physical activity as reported in physical activity recalls. RESULTS: After accounting for individual-level socioeconomic status, women who lived in lower-socioeconomic status neighbourhoods reported greater energy expenditure, but undertook less moderate physical activity, than women in moderate socioeconomic status neighbourhoods. In contrast, women living in higher socioeconomic status neighbourhoods reported more vigorous physical activity than women in moderate-socioeconomic status neighbourhoods. Although availability of physical activity resources did not appear to mediate any neighbourhood socioeconomic status associations, several significant interactions emerged, suggesting that women with low income or who live in lower-socioeconomic status neighbourhoods may differentially benefit from greater physical activity resource availability. DISCUSSION: Although we found expected relationships between residence in a lower-socioeconomic status neighbourhood and undertaking less moderate or vigorous physical activity among women, we also found that these same women reported greater overall energy expenditure, perhaps as a result of greater work or travel demands. Greater availability of physical activity resources nearby appears to differentially benefit women living in lower-socioeconomic status neighbourhoods and low-income women, having implications for policy-making and planning. PMID- 17873225 TI - King Saul, work-related stress and depression. PMID- 17873226 TI - Does financial disadvantage at older ages eliminate the potential for better health? AB - OBJECTIVE: Taller adult stature reflects early life advantages and is an indicator of improved economic and health outcomes, and thus the potential for better health, including reduced depression risk. As inadequate retirement pension provision is an increasing concern, we investigated whether health potential (indicated by height) was realised among those experiencing financial disadvantage in later life. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of the population in England aged over 50 years and not resident in an institution. Participants (n = 9106) were members of the English Longitudinal Study of Ageing. MAIN OUTCOME MEASURE: Depression assessed using the eight-item Center for Epidemiological Studies Depression Scale. RESULTS: Stratification by the lowest quintile of the net financial assets distribution defined adversity, and stature was dichotomised at the shortest quintile of height (sex standardised). After adjustment for sex, qualifications, occupation type, whether currently employed, age, ethnic origin and chronic illness, taller stature was associated with a statistically significant reduced risk of depression with an odds ratio of 0.7 (95% confidence interval 0.6 to 0.9) among those without financial disadvantage. No protection against depression was associated with taller stature among those with financial disadvantage (odds ratio 1.0; 95% confidence interval 0.8 to 1.3). Interaction testing confirmed effect modification by financial disadvantage for the association of height with depression (p = 0.005). CONCLUSIONS: Although taller stature, indicating favourable childhood conditions, is associated with a decreased risk of depression, this benefit is eliminated by financial disadvantage at older ages. Adequate financial provision for older people is required to maximise the health potential imparted by beneficial conditions in earlier life. PMID- 17873227 TI - Elvis to Eminem: quantifying the price of fame through early mortality of European and North American rock and pop stars. AB - BACKGROUND: Rock and pop stars are frequently characterised as indulging in high risk behaviours, with high-profile deaths amongst such musicians creating an impression of premature mortality. However, studies to date have not quantified differences between mortality experienced by such stars and general populations. OBJECTIVE: This study measures survival rates of famous musicians (n = 1064) from their point of fame and compares them to matched general populations in North America and Europe. DESIGN: We describe and utilise a novel actuarial survival methodology which allows quantification of excess post-fame mortality in pop stars. PARTICIPANTS: Individuals from North America and Europe performing on any album in the All-Time Top 1000 albums from the music genres rock, punk, rap, R&B, electronica and new age. RESULTS: From 3 to 25 years post fame, both North American and European pop stars experience significantly higher mortality (more than 1.7 times) than demographically matched populations in the USA and UK, respectively. After 25 years of fame, relative mortality in European (but not North American) pop stars begins to return to population levels. Five-year post fame survival rates suggest differential mortality between stars and general populations was greater in those reaching fame before 1980. CONCLUSION: Pop stars can suffer high levels of stress in environments where alcohol and drugs are widely available, leading to health-damaging risk behaviour. However, their behaviour can also influence would-be stars and devoted fans. Collaborations between health and music industries should focus on improving both pop star health and their image as role models to wider populations. PMID- 17873228 TI - Adult outcomes of binge drinking in adolescence: findings from a UK national birth cohort. AB - AIMS: The aim of the study was to determine outcomes in adult life of binge drinking in adolescence in a national birth cohort. DESIGN AND SETTING: Longitudinal birth cohort: 1970 British Birth Cohort Study surveys at 16 years (1986) and 30 years (2000). PARTICIPANTS: A total of 11 622 subjects participated at age 16 years and 11 261 subjects participated at age 30 years. MEASUREMENTS: At the age of 16 years, data on binge drinking (defined as two or more episodes of drinking four or more drinks in a row in the previous 2 weeks) and frequency of habitual drinking in the previous year were collected. Thirty-year outcomes recorded were alcohol dependence/abuse (CAGE questionnaire), regular weekly alcohol consumption (number of units), illicit drug use, psychological morbidity (Malaise Inventory) and educational, vocational and social history. FINDINGS: 17.7% of participants reported binge drinking in the previous 2 weeks at the age of 16 years. Adolescent binge drinking predicted an increased risk of adult alcohol dependence (OR 1.6, 95% CI 1.3 to 2.0), excessive regular consumption (OR 1.7, 95% CI 1.4 to 2.1), illicit drug use (OR 1.4, 95% CI 1.1 to 1.8), psychiatric morbidity (OR 1.4, 95% CI 1.1 to 1.9), homelessness (OR 1.6, 95% CI 1.1 to 2.4), convictions (1.9, 95% CI 1.4 to 2.5), school exclusion (OR 3.9, 95% CI 1.9 to 8.2), lack of qualifications (OR 1.3, 95% CI 1.1 to 1.6), accidents (OR 1.4, 95% CI 1.1 to 1.6) and lower adult social class, after adjustment for adolescent socioeconomic status and adolescent baseline status of the outcome under study. These findings were largely unchanged in models including both adolescent binge drinking and habitual frequent drinking as main effects. CONCLUSIONS: Adolescent binge drinking is a risk behaviour associated with significant later adversity and social exclusion. These associations appear to be distinct from those associated with habitual frequent alcohol use. Binge drinking may contribute to the development of health and social inequalities during the transition from adolescence to adulthood. PMID- 17873229 TI - Population-based survey methods to quantify associations between human rights violations and health outcomes among internally displaced persons in eastern Burma. AB - BACKGROUND: Case reports of human rights violations have focused on individuals' experiences. Population-based quantification of associations between rights indicators and health outcomes is rare and has not been documented in eastern Burma. OBJECTIVE: We describe the association between mortality and morbidity and the household-level experience of human rights violations among internally displaced persons in eastern Burma. METHODS: Mobile health workers in conflict zones of eastern Burma conducted 1834 retrospective household surveys in 2004. Workers recorded data on vital events, mid-upper arm circumference of young children, malaria parasitaemia status of respondents and household experience of various human rights violations during the previous 12 months. RESULTS: Under-5 mortality was 218 (95% confidence interval 135 to 301) per 1000 live births. Almost one-third of households reported forced labour (32.6%). Forced displacement (8.9% of households) was associated with increased child mortality (odds ratio = 2.80), child malnutrition (odds ratio = 3.22) and landmine injury (odds ratio = 3.89). Theft or destruction of the food supply (reported by 25.2% of households) was associated with increased crude mortality (odds ratio = 1.58), malaria parasitaemia (odds ratio = 1.82), child malnutrition (odds ratio = 1.94) and landmine injury (odds ratio = 4.55). Multiple rights violations (14.4% of households) increased the risk of child (incidence rate ratio = 2.18) and crude (incidence rate ratio = 1.75) mortality and the odds of landmine injury (odds ratio = 19.8). Child mortality risk was increased more than fivefold (incidence rate ratio = 5.23) among families reporting three or more rights violations. CONCLUSIONS: Widespread human rights violations in conflict zones in eastern Burma are associated with significantly increased morbidity and mortality. Population-level associations can be quantified using standard epidemiological methods. This approach requires further validation and refinement elsewhere. PMID- 17873230 TI - Diagnosis-specific sick leave as a risk marker for disability pension in a Swedish population. AB - OBJECTIVE: To investigate diagnosis-specific sick leave as a risk marker for subsequent disability pension. DESIGN: A prospective population based cohort study. Exposure to a new medically certified sick leave episode of more than seven days by diagnosis during 1985 was examined in relation to incident cause specific disability pension through 1996. PARTICIPANTS: The total non-retired population of one Swedish county aged 16 to 49 years, alive and not in receipt of a disability pension at the end of 1985 (176 629 persons; 51% men). MAIN RESULTS: To eliminate confounding by sick leaves that translate into a disability pension, the follow up period for disability pension was started five years after the assessment of sick leave. After adjustment for demographic characteristics, the risk of disability pension from mental disorders was 14.1 times higher (95% confidence interval (CI), 12.1 to 16.4) for those with sick leave for mental disorders than for those with no sick leave. The corresponding hazard ratio for sick leave and disability pension within diagnostic category was 5.7 (95% CI, 5.3 to 6.2) for musculoskeletal diseases and 13.0 (7.7 to 21.8) for gastrointestinal diseases. Irrespective of diagnoses, the hazard ratio for sick leave and disability pension was 3.0 (2.9 to 3.1). CONCLUSIONS: Sick leave may provide an important risk marker for identifying groups at high risk of a disability pension, especially for psychiatric diagnoses. PMID- 17873231 TI - Development of a short version of the sense of coherence scale for population survey. AB - A three-item sense of coherence (SOC) scale was developed, incorporating the definitions of the three subordinate concepts of SOC for use in population surveys. A cross-sectional internet survey was conducted in the latter part of July 2006. Cronbach's alpha was 0.84. The correlation coefficient of SOC-13 and the newly devised University of Tokyo Health Sociology version of the SOC Scale (SOC-3-UTHS) was 0.51. As regards correlation with a health index, SOC-3-UTHS had a significant association, although this association was somewhat weaker than that of SOC-13. Therefore, certain levels of convergent and concurrent validities of SOC-3-UTHS have been indicated. PMID- 17873232 TI - Determining the lifetime density function using a continuous approach. AB - OBJECTIVE: To apply a continuous hazard function approach to calculate the lifetime density function (LDF) at any age, and to compare the life expectancies derived from the LDF with those obtained with standard life table (SLT) methods. METHODS: Age-specific mortality rates were modeled through a continuous hazard function. To construct the cumulative hazard function, appropriate integration limits were considered as continuous random variables. The LDF at any age was defined on the basis of the elemental relationships with the cumulative hazard function. Life expectancies were calculated for a particular set of mortality data using the SLT approach and the expectancy of the LDF defined. APPLICATIONS AND COMPARISONS: The proposed approach was applied using mortality data from the 2001 census of Catalonia (Spain). A Gompertz function was used to model the observed age-specific mortality rates, which fitted the observed data closely. The LDF and the life expectancy, median and standard deviation of the LDF were derived using mathematical software. All differences, in percentages, between the life expectancies obtained from the two methods were 1.1% or less. CONCLUSIONS: The LDF gives a wider interpretation of life duration, by extending a deterministic value like life expectancy to a fully informative measure like the LDF. PMID- 17873238 TI - Effects of the oral, direct factor xa inhibitor rivaroxaban on platelet-induced thrombin generation and prothrombinase activity. AB - Rivaroxaban (BAY 59-7939) is an oral, direct factor Xa inhibitor in advanced development. This study was undertaken to investigate its effects on thrombin generation. In this placebo-controlled, randomized, crossover study, 12 healthy subjects received rivaroxaban (single 5- or 30-mg dose) or placebo. Thrombin generation was investigated by measuring the endogenous thrombin potential and prothrombinase-induced clotting time. Maximal effect of rivaroxaban was observed 2 hours after drug administration: prothrombinase-induced clotting time was prolonged 1.8 and 2.3 times baseline after rivaroxaban 5 and 30 mg, respectively. Collagen-induced endogenous thrombin potential was reduced by approximately 80% and approximately 90% compared with baseline after rivaroxaban 5 and 30 mg, respectively, and tissue factor-induced endogenous thrombin potential was reduced by approximately 40% (5 mg) and approximately 65% (30 mg), respectively. Thrombin generation remained inhibited for 24 hours. There was a close correlation between plasma concentration of rivaroxaban and prolongation of prothrombinase-induced clotting time and reduction in endogenous thrombin potential. Rivaroxaban strongly inhibits platelet-induced thrombin generation, after activation of either platelets or the coagulation pathway, even in the presence of minimal factor Xa inhibition in plasma. PMID- 17873239 TI - EPSDT preventive services in a low-income pediatric population: impact of a nursing protocol. AB - Medicaid mandates coverage of clinical preventive services for children under the Early and Periodic Screening, Diagnosis, and Treatment program (EPSDT). This article assesses the usefulness of a nursing protocol for delivering comprehensive EPSDT services to pediatric patients during any primary care visit. Secondary data from a recent controlled trial were analyzed. An intervention group received the clinical protocol (n = 514 children in a low-income pediatric clinic), whereas data from a "usual care" comparison group were obtained from medical records (n = 115 children). The nursing protocol included 52 items corresponding to EPSDT services and was administered by a prevention nurse. In the intervention group, 11 605 out of 11 607 (approximately 100.0%) EPSDT service needs were initiated, as compared to 21.2% (572 out of 2695) in the comparison group (P < .001). The study demonstrates the feasibility of using a nursing protocol to integrate EPSDT clinical preventive services into pediatric visits. PMID- 17873240 TI - Child sexual abuse: can anatomy explain the presentation? AB - This article discusses a 4-year-old girl who displayed behavioral symptoms consistent with posttraumatic stress disorder. She was recently placed in foster care due to emotional and physical neglect. During her clinic visit, she disclosed being sexually abused by her father with a knife. Results of her general and anogenital physical examinations were normal. The case discussion proposes an explanation for how a maltreated child (1) develops behavioral problems, (2) has a normal genital examination despite the history of sexual abuse, and (3) has an implausible disclosure of her father hurting her with a knife. As part of the Integrating Basic Science into Clinical Teaching Initiative series, basic science principles are the method of explanation. The case discussion is an attempt to understand the science responsible for the disease that is present and make that understanding useful for future clinical problem solving. PMID- 17873241 TI - Wheezing child. AB - This case discussion is part of the Integrating Basic Science into Clinical Teaching Initiative. It is intended to examine wheezing as a symptom and to describe the underlying physiology that explains the physical findings and blood gas features in an attempt to localize the site of obstruction. The information contained in this case is a compilation and derived from 2 similar patients. This case discussion describes a 13-month-old girl who presents with wheezing and respiratory distress. A close examination of her physical findings and blood gas analysis indicate that she is experiencing overall alveolar hypoventilation without significant hypoxemia, suggesting her airway obstruction is located above the carina. Subsequent investigations reveal a right aortic arch and vascular ring as the cause of her symptoms. An understanding of the physiology of airway obstruction and pulmonary gas exchange allows for better localization of sites of airway obstruction and the institution of appropriate diagnostic tests and therapy. PMID- 17873242 TI - Serum zinc levels in children with simple febrile seizure. AB - A prospective case-control study was conducted in a major tertiary care hospital for children during June 2005 to May 2006 on children aged between 3 months and 5 years to compare serum zinc levels in 38 cases of simple febrile seizure and 38 age-matched controls. The mean serum zinc levels in cases and controls were 32.17 and 87.6 microg/dL, respectively. This difference was statistically significant ( P < .001). We conclude that Indian children with febrile seizure had low serum zinc levels, and zinc supplementation to reduce the incidence of febrile seizure should be investigated. PMID- 17873243 TI - Potentially avoidable pediatric hospitalizations as defined by the Agency for Healthcare Research and Quality: what do they tell us about disparities in child health? AB - This study was conducted to determine if the Agency for Healthcare Research and Quality's newly established pediatric quality monitors, which measure potentially avoidable hospitalizations, are useful in detecting disparities in health care delivery. Data for all hospital discharges in Tennessee in 2002 were evaluated for the 5 pediatric discharge monitors identified by the Agency for Healthcare Research and Quality. These diagnoses were asthma, short-term complications of diabetes, gastroenteritis, urinary tract infection, and perforated appendix. Black children were more likely to be discharged with the diagnoses of asthma and short-term diabetes complications. Publicly insured children were more likely than commercially insured children to be discharged with each of the 5 potentially avoidable hospitalizations. The results show that black children and children insured by public programs have significantly different discharge rates for pediatric potentially avoidable hospitalizations than do white children or commercially insured children. This could be the result of less access to high quality ambulatory care. PMID- 17873244 TI - Use of selective serotonin reuptake inhibitors by pediatricians: comparing attitudes of primary care pediatricians and child and adolescent psychiatrists. AB - To compare attitudes regarding a pediatrician's role in prescribing selective serotonin reuptake inhibitors for children and adolescents, surveys were mailed to 338 primary care pediatricians and 75 child and adolescent psychiatrists; half responded. Child and adolescent psychiatrists were significantly more likely than primary care pediatricians to agree that selective serotonin reuptake inhibitors are safe and effective when used for children and adolescents. Primary care pediatricians were significantly more likely than child and adolescent psychiatrists to agree that black box warnings have changed their prescribing practices. Both had similar beliefs about whether antidepressants should be prescribed only by psychiatrists and whether pediatricians should initiate selective serotonin reuptake inhibitor therapy, without or after consulting a psychiatrist. These data suggest that among child and adolescent psychiatrists and primary care pediatricians, agreement about the pediatrician's role in using selective serotonin reuptake inhibitors therapy is lacking. Strategies that enhance communication and endorse support for defined roles of primary care pediatricians and child and adolescent psychiatrists will ensure that children with mental health needs are treated safely and appropriately. PMID- 17873245 TI - Occult methicillin-resistant Staphylococcus aureus abscesses in 2 pediatric patients. AB - Methicillin-resistant Staphylococcus aureus (MRSA) infections have become more common over the last decade. Recently, severe MRSA infections including necrotizing pneumonia, purpura fulminans, and rapidly progressive skin abscesses have been reported. These severe infections frequently have been associated with the virulence factor Panton-Valentine leukocidin (PVL). Two unusual cases of occult deep tissue abscesses in children who had family members with a history of severe MRSA skin abscesses are presented in this article. Both children initially presented with fever without a focus. Deep tissue MRSA (PVL positive) abscesses evolved. Empiric antibiotic therapy for MRSA should be considered for infants and children who are hospitalized with occult fever and who have a family member with a history of MRSA infection. PMID- 17873246 TI - A Prospective Study of Adherence and Virologic Failure in HIV-Infected Patients: Role of a Single Determination of Plasma Levels of Antiretroviral Medications. AB - This study explores the contribution of a single determination of plasma levels for measuring adherence by means of forecasting virologic failure. Adherence was measured by questionnaires, punctuality at appointments to withdraw drugs, and plasma levels. Virologic failure was considered when 2 detectable consecutive viral loads were observed in 2 consecutive determinations with at least 1 month between them. Univariant analysis, logistic regression, and receiver operating characteristic curves were carried out. In 29 cases, virologic failure was observed. The lowest incidence was found in patients considered adherent by plasma levels and highest in those who declared nonfulfillment. The combination of methods increased the association of the incidence of virologic failure with nonadherence. The use of questionnaires plus pharmacy information implies a gain in sensitivity and a slight loss of specificity. There is a high incidence of virologic failure in these patients and a strong link with their classification as nonadherent with methods such as questionnaires and pharmacy collection information. Plasma levels do not contribute much to the prediction of virologic failure. PMID- 17873247 TI - Localized Pulmonary Mycobacterium avium Disease in HIV-Infected Patients Without Access to HAART. PMID- 17873248 TI - Lymphadenopathy--An Important Guiding Tool for Detecting Hidden HIV-Positive Cases: A 6-Year Study. AB - Lymphadenopathy is one of the leading and persistent signs during the progression of human immunodeficiency virus (HIV) infection. Lymphadenopathy, as a clinical sign, can become one of the important guiding tools for detecting hidden HIV positive cases. The present study was conducted to assess the incidence of HIV positivity in previously undiagnosed patients of HIV presenting with lymphadenopathy, comparing it with the current trends of HIV infection in the community, and to ascertain the etiology of lymphadenopathy in HIV-positive and HIV-negative cases. Over a period of 6 years, a total of 1082 cases of extra inguinal lymphadenopathy were screened for HIV infection. Simultaneously, fine needle aspiration cytology of the enlarged lymph nodes was performed to know the etiology. The incidence of HIV positivity was found to be 2.3% among the patients presenting with lymphadenopathy. Among the HIV-positive cases, tuberculous lymphadenopathy was found in 60% of cases as compared to 28% of cases in HIV negative cases. Alarmingly high incidence of HIV infection among the lymphadenopathy cases has been observed. This necessitates the importance of exercising vigilance, caution, and a high degree of suspicion while dealing with patients of lymphadenopathy, to protect ourselves as well as a much larger population at risk from this scourge. PMID- 17873249 TI - Communication and decision making in cancer care: setting research priorities for decision support/patients' decision aids. AB - The following is a summary report from a special symposium titled, "Translating Research into Practice: Setting a Research Agenda for Clinical Decision Tools in Cancer Prevention, Early Detection, and Treatment," that was held on 23 October 2005 in San Francisco at the Annual Meeting of the Society for Medical Decision Making (SMDM). The symposium was designed to answer the question: "What are the top 2 research priorities in the field of patients' cancer-related decision aids?" After introductory remarks by Dr. Barry, each of four panelists-Drs. Hilary Llewellyn-Thomas, Ellen Peters, Laura Siminoff, and Dale Collins-addressed the question and provided their rationale during prepared remarks. The moderator, Dr. Michael Barry, then facilitated a discussion between the panelists, with input from the audience, to further explore and add to the various proposed research questions. Finally, Dr. Amber Barnato conducted a simple vote count (see Table 1) to prioritize the panelists' and the audience's recommendations. PMID- 17873250 TI - A meta-analysis of the effects of presenting treatment benefits in different formats. AB - PURPOSE: The purpose of this article is to examine the effects of presenting treatment benefits in different formats on the decisions of both patients and health professionals. Three formats were investigated: relative risk reductions, absolute risk reductions, and number needed to treat or screen. METHODS: A systematic review of the published literature was conducted. Articles were retrieved by searching a variety of databases and screened for inclusion by 2 reviewers. Data were extracted on characteristics of the subjects and methodologies used. Log-odds ratios were calculated to estimate effect sizes. RESULTS: A total of 24 articles were retrieved that reported on 31 unique experiments. The meta-analysis showed that treatments were evaluated more favorably when the relative risk format was used rather than the absolute risk or number needed to treat format. However, a significant amount of heterogeneity was found between studies, the sources of which were explored using subgroup analyses and metaregression. Although the subgroup analyses revealed smaller effect sizes in the studies conducted on physicians, the metaregression showed that these differences were largely accounted for by other features of the study design. Most notably, variations in effect sizes were explained by the particular wordings that the studies had chosen to use for the relative risk and absolute risk reductions. CONCLUSIONS: The published literature has consistently demonstrated that relative risk formats produce more favorable evaluations of treatments than absolute risk or number needed to treat formats. However, the effects are heterogeneous and seem to be moderated by key differences between the methodologies used. PMID- 17873251 TI - Rethinking the objectives of decision aids: a call for conceptual clarity. AB - Health decision aids are a potentially valuable adjunct to patient-physician communication and decision making. Although the overarching goal of decision aids -to help patients make informed, preference-sensitive choices--is widely accepted, experts do not agree on the means to achieve this end. In this article, the authors critically examine the theoretical basis and appropriateness of 2 widely accepted criteria used to evaluate decision aids: values clarification and reduction of decisional conflict. First, they argue that although clarifying values is central to decision making under uncertainty, it is not clear that decision aids--as they have been conceived and operationalized so far--can and should be used to achieve this goal. The pursuit of clarifying values, particularly values clarification exercises, raises a number of ethical, methodological, and conceptual issues, and the authors suggest research questions that should be addressed before values clarification is routinely endorsed. Second, the authors argue that the goal of reducing decisional conflict is conceptually untenable and propose that it be eliminated as an objective of decision aids. PMID- 17873252 TI - Shared decision making in the medical encounter: are we all talking about the same thing? AB - OBJECTIVE: This article aims to explore 1) whether after all the research done on shared decision making (SDM) in the medical encounter, a clear definition (or definitions) of SDM exists; 2) whether authors provide a definition of SDM when they use the term; 3) and whether authors are consistent, throughout a given paper, with respect to the research described and the definition they propose or cite. METHODS: The authors searched different databases (Medline, HealthStar, Cinahl, Cancerlit, Sociological Abstracts, and Econlit) from 1997 to December 2004. The keywords used were informed decision making and shared decision making as these are the keywords more often encountered in the literature. The languages selected were English and French. RESULTS: The 76 reported papers show that 1) several authors clearly define what they mean by SDM or by another closely related phrase, such as informed shared decision making. 2) About a third of the papers reviewed (25/76) cite these authors although 8 of them do not use the term in a manner consistent with the definition cited. 3) Certain authors use the term SDM inconsistently with the definition they propose, and some use the terms informed decision making and SDM as if they were synonymous. 4) Twenty-one papers do not provide or cite any definition, or their use of the term (i.e., SDM) is not consistent with the definition they provide. CONCLUSION: Although several clear definitions of shared decision making have been proposed, they are cited by only about a third of the papers reviewed. In the other papers, authors refer to the term without specifying or citing a definition or use the term inconsistently with their definition. This is a problem because having a clear definition of the concept and following this definition are essential to guide and focus research. Authors should use the term consistently with the identified definition. PMID- 17873253 TI - Participation in medical decision making: the patients' perspective. AB - PURPOSE: Variability in reports of patients' preferences to participate in decision making may be due in part to a lack of understanding about how patients conceptualize their participation. The authors sought to learn more about how patients view their involvement in decisions related to their health care. METHODS: The authors conducted individual interviews to allow patients to frame the decision-making process from their own perspective. The constant comparative method approach to analysis was employed to ensure that the analysts defined the codes in a consistent manner. RESULTS: Twenty-six persons were interviewed. The main themes discussed by the participants reflecting how they viewed their involvement in medical decision making are the following: 1) decision making is often an ongoing process in which patient participation may change over time, 2) decision making is performed within an extended social context, 3) the decisions patients report being involved in are often distinct from those traditionally studied (choice of treatment or screening strategies), 4) patient involvement in decision making occurs in response to physicians' recommendations, and 5) patients make choices in the context of their specific illness perceptions. CONCLUSIONS: Participants in this study view their participation in decision making as including ideas distinct from those traditionally discussed by researchers. These findings suggest that the variability in patient participation noted in previous studies may be due in part to limitations in study design. PMID- 17873254 TI - Patient decision aids to support clinical decision making: evaluating the decision or the outcomes of the decision. AB - Decision aids (DAs) are tools to support patients make informed health decisions with their practitioner. They aim to improve patient knowledge of options, incorporate patient preferences and values, and increase patient involvement in health decision making. Increasingly, the debate about DAs concerns how they should be implemented in practice, with the view that DAs are superior to usual clinical care in facilitating health decisions. The authors challenge this view and suggest that DA research has focused on measures of decision process, leaving the effects on the outcome of the decision relatively unknown. It is still unclear in which conditions DAs are better for patient health and well-being than clinician-led decisions. The authors present a new randomized design to examine the effects of DA-supported patient choice on patient-centered outcomes to identify where DAs are best implemented in clinical practice. In this design, patients are randomized to 1 of 4 arms: intervention A, intervention B, choice of either intervention supported by a clinician, or choice of either intervention supported by a decision aid. Health and quality of life measured over the long term are presented as the primary outcomes. The authors propose that this design will allow the proper assessment of different modes of decision making. PMID- 17873255 TI - Do patient decision aids meet effectiveness criteria of the international patient decision aid standards collaboration? A systematic review and meta-analysis. AB - OBJECTIVE: To describe the extent to which patient decision aids (PtDAs) meet effectiveness standards of the International Patient Decision Aids Collaboration (IPDAS). DATA SOURCES: Five electronic databases (to July 2006) and personal contacts (to December 2006). RESULTS: Among 55 randomized controlled trials, 38 (69%) used at least 1 measure that mapped onto an IPDAS effectiveness criterion. Measures of decision quality were knowledge scores (27 trials), accurate risk perceptions (12 trials), and value congruence with the chosen option (3 trials). PtDAs improved knowledge scores relative to usual care (weighted mean difference [WMD] = 15.2%, 95% confidence interval [CI] = 11.7 to 18.7); detailed PtDAs were somewhat more effective than simpler PtDAs (WMD = 4.6%, 95% CI = 3.0 to 6.2). PtDAs with probabilities improved accurate risk perceptions relative to those without probabilities (relative risk = 1.6, 95% CI = 1.4 to 1.9). Relative to simpler PtDAs, detailed PtDAs improved value congruence with the chosen option. Only 2 of 6 IPDAS decision process criteria were measured: feeling informed (15 trials) and feeling clear about values (13 trials). PtDAs improved these process measures relative to usual care (feeling uninformed WMD = -8.4, 95% CI = -11.9 to -4.8; unclear values WMD = -6.3, 95% CI = -10.0 to -2.7). There was no difference in process measures when detailed and simple PtDAs were compared. CONCLUSIONS: PtDAs improve decision quality and the decision process's measures of feeling informed and clear about values; however, the size of the effect varies across studies. Several IPDAS decision process measures have not been used. Future trials need to use a minimum data set of IPDAS evaluation measures. The degree of detail PtDAs require for positive effects on IPDAS criteria should be explored. PMID- 17873256 TI - Communicating the uncertainty of harms and benefits of medical interventions. AB - BACKGROUND: There is growing interest in shared medical decision making among patients, physicians, and policy makers. This requires patients to interpret increasing amounts of medical information, much of which is uncertain. Little is known about the optimal approaches to or outcomes of communicating uncertainty about the risks and benefits of treatments. METHODS: The authors reviewed the literature on various issues related to uncertainty in decision making: conceptualizing uncertainty, identifying its potential sources, assessing uncertainty, potential methods of communicating uncertainty, potential outcomes of communicating uncertainty, and current practices and recommendations by expert groups on communicating uncertainty. RESULTS: There are multiple sources of uncertainty in most medical decisions. There are conceptual differences in how researchers define uncertainty and its sources, as well as in its measurement. The few studies that have assessed alternate means of communicating uncertainty dealt mostly with presenting uncertainty about probabilities. Both patients' and physicians' interpretation of and responses to uncertainty may depend on their personal characteristics and values and may be affected by the manner in which uncertainty is communicated. CONCLUSIONS: Research has not yet identified best practices for communicating uncertainty to patients about harms and benefits of treatment. More conceptual, qualitative, and quantitative studies are needed to explore fundamental questions about how people process, interpret, and respond to various types of uncertainty inherent in clinical decisions. PMID- 17873257 TI - Are patient decision aids the best way to improve clinical decision making? Report of the IPDAS Symposium. AB - This article reports on the International Patient Decision Aid Standards Symposium held in 2006 at the annual meeting of the Society for Medical Decision Making in Cambridge, Massachusetts. The symposium featured a debate regarding the proposition that "decision aids are the best way to improve clinical decision making.'' The formal debate addressed the theoretical problem of the appropriate gold standard for an improved decision, efficacy of decision aids, and prospects for implementation. Audience comments and questions focused on both theory and practice: the often unacknowledged roots of decision aids in expected utility theory and the practical problems of limited patient decision aid implementation in health care. The participants' vote on the proposition was approximately half for and half against. PMID- 17873258 TI - The drug facts box: providing consumers with simple tabular data on drug benefit and harm. AB - CONTEXT: Direct-to-consumer drug ads have been criticized for providing inadequate and misleading information. Requiring ads to include a table with data on drug benefits and side effects (derived from clinical trials) could help, provided that consumers understand such tabular information. OBJECTIVE: To determine if people could understand and use a 9-row x 2-column "study findings table'' presenting expected outcomes (both beneficial and harmful) with and without a drug. SUBJECTS: A convenience sample of 274 participants: 186 recruited from alumni of Dartmouth's "Community Medical School'' public lecture series and Dartmouth Hitchcock's Center for Shared Decision Making and 88 veterans and their families recruited from waiting rooms in the Veterans Affairs outpatient clinic, White River Junction, Vermont. DESIGN: Cross-sectional survey. Participants were tested on their comprehension of the study findings table about the drug tamoxifen used for the primary prevention of breast cancer--with no instructions on how to use the table. MAIN OUTCOME MEASURE: Five comprehension questions testing how well participants could read and use the table with drug benefits and side effects data. RESULTS: On average, participants correctly answered 4 of the 5 table comprehension questions: 89% correctly used the table to determine the percentage of women given tamoxifen who got a blood clot in their legs or lungs, and 71% were able to use data in the table to calculate the absolute difference in the proportion of women who got breast cancer in the tamoxifen v. the placebo group. Most participants were also able to use the table to make comparisons. CONCLUSION: Most participants--even those with lower formal educational attainment--were able to understand and use the tabular data. PMID- 17873259 TI - Numeric, verbal, and visual formats of conveying health risks: suggested best practices and future recommendations. AB - Perception of health risk can affect medical decisions and health behavior change. Yet the concept of risk is a difficult one for the public to grasp. Whether perceptions of risk affect decisions and behaviors often relies on how messages of risk magnitudes (i.e., likelihood) are conveyed. Based on expert opinion, this article offers, when possible, best practices for conveying magnitude of health risks using numeric, verbal, and visual formats. This expert opinion is based on existing empirical evidence, review of papers and books, and consultations with experts in risk communication. This article also discusses formats to use pertaining to unique risk communication challenges (e.g., conveying small-probability events, interactions). Several recommendations are suggested for enhancing precision in perception of risk by presenting risk magnitudes numerically and visually. Overall, there are little data to suggest best practices for verbal communication of risk magnitudes. Across the 3 formats, few overall recommendations could be suggested because of 1) lack of consistency in testing formats using the same outcomes in the domain of interest, 2) lack of critical tests using randomized controlled studies pitting formats against one another, and 3) lack of theoretical progress detailing and testing mechanisms why one format should be more efficacious in a specific context to affect risk magnitudes than others. Areas of future research are provided that it is hoped will help illuminate future best practices. PMID- 17873260 TI - Can computerized decision support help patients make complex treatment decisions? A randomized controlled trial of an individualized menopause decision aid. AB - PURPOSE: To compare the effectiveness of an individualized decision aid (DA) with standard educational materials on decisions about menopausal treatments and to assess the feasibility of integrating this DA into clinical practice, with and without coaching. METHODS: We conducted a 3-armed randomized controlled trial in 3 clinics, enrolling menopausal women between the ages of 45 and 65 years with primary care appointments. Of the 145 women included, 99 completed a 2-week follow-up. The control group received generic educational materials, 1 intervention group received an individualized computer-generated DA mailed to patients and their clinicians before clinic appointment, and the 2nd intervention group received the same DA along with coached care before clinic appointment (DA + CC). Decisional conflict, satisfaction, and knowledge were measured 2 weeks after clinic appointment. RESULTS: Participants' mean age was 52 years, and 97% were white. Most women (98%) read all or most of the documents. Decisional conflict was significantly lower in both intervention groups but not in the control group. DA reduced decisional conflict from preintervention to postintervention (pre-post change) by 0.70 (SD = 0.56) points (on a 1-5 scale), compared to reductions of 0.51 (SD = 0.51) and 0.09 (SD = 0.44) for the DA + CC group and the control group, respectively. Satisfaction with the decision made was significantly higher at 2 weeks in the DA v. control group. Self-reported knowledge significantly improved in DA + CC compared to controls. CONCLUSION: Our decision aid lowered decisional conflict and improved patient satisfaction; adding coaching provided little additional benefit. PMID- 17873261 TI - "It's my body'': does patient involvement in decision making reduce decisional conflict? AB - OBJECTIVE: This study explores how much people with HIV/AIDS wanted and how much they actually perceived being involved in the decision to take or not to take antiretroviral treatment (ART). The congruence between desired and perceived decisional involvement was also related to decisional conflict. METHOD: Cross sectional (N = 79), the Control Preferences Scale assessed patients' preferred versus perceived role in treatment decision making. The Decisional Conflict Scale measured patients' perceived difficulties in decision making. RESULTS: Although a minority of patients (32%) perceived their role as shared decision making, the majority (59%) preferred shared decision making. Some did not desire shared decision making, with 28% preferring to decide on their own versus 13% wanting their physicians to decide for them. Overall, 58% did not feel they had achieved their desired role in decision making (half of whom perceived more control and the other half less control than preferred). Participants declining ART felt more pressure to decide alone compared with those taking ART (P < 0.01). Decisional conflict was expressed by 53% and was highest when physicians unilaterally made decisions about ART for patients who preferred shared decision making (P < 0.001). CONCLUSIONS: In this study, most physicians do not meet their patients' desired roles in decision making. One-third of people taking ART feel less involved than they desire. More critically, half of those declining ART feel pressured to decide alone, suggesting that physicians should remain involved in the decision to reject treatment, as this requires careful monitoring and periodical revisiting. Because lack of shared decision making is related to decisional conflict, physicians may reduce decisional conflict by meeting patients' desires for shared decision making. PMID- 17873262 TI - Patterns of use of handheld clinical decision support tools in the clinical setting. AB - OBJECTIVES: To assess the patterns of use of handheld clinical decision support tools by internal medicine residents in clinical settings. METHODS: Eighty-two internal medicine residents were given personal digital assistants (PDAs) containing a suite of clinical decision support (CDS) programs. A tracking program was used to prospectively track program use during the study period, and a follow-up survey regarding self-reported program use was administered after the study period. Patterns of program use from the tracking data were compared to the data from the self-report survey. RESULTS: Sixty-eight residents were followed using the tracking data. Residents used an average of 1.81 CDS programs (SD: 1.57; range, 0-5) per month. Forty-nine residents completed the self-report survey. Residents reported using an average of 3.15 (SD: 1.61) and 3.92 (SD: 1.40) CDS programs during a typical clinic session and inpatient day, respectively. In both inpatient and outpatient settings and for both methods of assessing program use, 2 programs (Epocrates and MedCalc) were used more often than the other programs. No association was observed between age, gender, race, and PGY level with the use of handheld clinical decision support tools for either tracked or self-report data. The self-report data show higher estimates of CDS program use than the tracking data in the clinical setting. CONCLUSIONS: The data show that physicians prefer to use certain handheld CDS tools in clinical settings. Drug references and medical calculators have been consistently used more than clinical prediction rules and diagnostic systems. Self-report survey instruments may overestimate recorded use of CDS programs. PMID- 17873263 TI - Primary prevention of cardiovascular diseases in general practice: mismatch between cardiovascular risk and patients' risk perceptions. AB - OBJECTIVE: Guidelines on primary prevention of cardiovascular disease (CVD) emphasize identifying high-risk patients for more intensive management, but patients' misconceptions of risk hamper implementation. Insight is needed into the type of patients that general practitioners (GPs) encounter in their cardiovascular prevention activities. How appropriate are the risk perceptions and worries of patients with whom GPs discuss CVD risks? What determines inappropriate risk perception? METHOD: Cross-sectional study in 34 general practices. The study included patients aged 40 to 70 years with whom CVD risk was discussed during consultation. After the consultation, the GPs completed a registration form, and patients completed a questionnaire. Correlations between patients' actual CVD risk and risk perceptions were analyzed. RESULTS: In total, 490 patients were included. In 17% of the consultations, patients were actually at high risk. Risk was perceived inappropriately by nearly 4 in 5 high-risk patients (incorrect optimism) and by 1 in 5 low-risk patients (incorrect pessimism). Smoking, hypertension, and obesity were determinants of perceiving CVD risk as high, whereas surprisingly, diabetic patients did not report any anxiety about their CVD risk. Men were more likely to perceive their CVD risk inappropriately than women. CONCLUSION: In communicating CVD risk, GPs must be aware that they mostly encounter low-risk patients and that the perceived risk and worry do not necessarily correspond with the actual risk. Incorrect perceptions of CVD risk among men and patients with diabetes were striking. PMID- 17873264 TI - The value of Bayes theorem in the interpretation of subjective diagnostic findings: what can we learn from agreement studies? AB - The Bayes theorem is advocated as the appropriate measure for the weight of evidence in medical decision making. It is based on the calculation of posttest probability as a function of the accuracy of the test and pretest probability. Nevertheless, for subjective diagnostic findings, there might be substantial variability in the accuracy among human observers, making the point estimate of posttest probability imprecise. Although there is limited evidence regarding the actual variability of accuracy among observers for the majority of diagnostic findings, classical observer agreement studies provide us with an indirect estimate of such variability. The aim of this work was to explicate the relationship between observer disagreement and variability of posttest probability. Using a random effects signal detection model with 3 stochastic components (between subject, between observer, and residual variations), the authors modeled diagnostic tests with various characteristics and calculated the expected between-observer disagreement and 95% interval of the observers' posttest probability. For the majority of simulated conditions, variation in posttest probability was surprisingly high, even in the presence of substantial agreement. Although the model is based on parametric assumptions, these results are a clue to a source of inaccuracy in the calculation of posttest probability. Practitioners should be aware of such variation in their clinical practice, and diagnostic studies need to develop strategies to address this uncertainty. PMID- 17873265 TI - Requirements for veterinary research and the recruitment of veterinary surgeons into research. AB - Veterinary science plays a crucial role in society and it is important that veterinarians are involved. However, there are concerns about a growing gap in the quality of veterinary science compared with other biomedical sciences, and about falling recruitment of veterinarians into research. Andrea Nolan and Massimo Palmarini, on behalf of the rcvs Research Subcommittee, discuss these concerns and the steps being taken to encourage more veterinary graduates into a career in research. PMID- 17873266 TI - Efficacy of cleaning and disinfection on pig farms in Ireland. AB - Little is known about the effectiveness of the cleaning and disinfection methods used on commercial pig farms either in Ireland or worldwide. A National Salmonella Control Programme was implemented in Ireland in August 2002 to monitor and control the infection of pigs with Salmonella species. Commercial pig herds must be categorised according to their Salmonella status as either category 1, 2 or 3, having a serological prevalence of infection with Salmonella serotypes up to 10 per cent, between 10 and 50 per cent or more than 50 per cent, respectively. The aim of this study was to assess the efficacy of washing and disinfecting finisher units on category 1 and category 3 farms in reducing or eliminating the levels of contamination. Counts of Enterobacteriaceae were used as indicators of the contamination of the environment with enteric bacteria, which could include Salmonella species. Samples were taken from the pen floors, feeders and drinkers of seven category 1 and seven category 3 farms, and Enterobacteriaceae and salmonellae were enumerated in each sample. The results suggested that intensive cleaning and disinfection was effective at reducing levels of Enterobacteriaceae on the pen floors of both categories, but that residual contamination remained on the surfaces of the feeders and drinkers on all the farms, particularly on the category 3 farms. PMID- 17873267 TI - Review of pathophysiology and clinical management of narcolepsy in dogs. AB - Narcolepsy is a chronic sleep disorder that affects human beings and animals. Up to 17 breeds of dogs are affected sporadically, and familial forms occur in dobermanns, labrador retrievers and dachshunds. These dogs display characteristics strikingly similar to those of human narcolepsy, including cataplexy (a sudden loss of muscle tone in response to emotional stimulation) and a shorter sleep latency. It has recently been shown that the aetiology of both the familial form (receptor null mutation) and the sporadic form (loss of ligand production) of canine narcolepsy is associated with a deficit in hypocretin/orexin neurotransmission. Hypocretin deficiency can be detected by the measurement of hypocretin-1 in cerebrospinal fluid, and this could be used to diagnose hypocretin ligand deficient cases in clinical practice. Narcolepsy is neither progressive nor life-threatening, but the clinical signs persist throughout life, and lifelong treatment and care are required. This article reviews the recent progress in narcolepsy research in dogs, and describes the diagnosis and treatment of the disease. PMID- 17873268 TI - Sensitive test for screening for Staphylococcus aureus in bovine mastitis by broth cultivation and PCR. AB - An assay was developed and evaluated for screening for Staphylococcus aureus in milk samples from cases of bovine mastitis by overnight cultivation in a broth containing 7.5 per cent sodium chloride, followed by pcr to amplify the nuc gene. The assay could detect concentrations of S aureus as low as 1 colony-forming unit/ml milk. Among 106 milk samples collected from individual quarters of lactating cows in one dairy herd and from a bulk tank, S aureus was detected in nine samples by the pcr assay but in only three samples by conventional microbiological culture. PMID- 17873269 TI - Isolation of European bat lyssavirus type 2 from a Daubenton's bat (Myotis daubentonii) in Shropshire. PMID- 17873270 TI - Prevalence of attaching and effacing Escherichia coli serogroup O103 in orphan lambs on an open farm in eastern England. PMID- 17873271 TI - Prolonged gestation in two Belgian blue cows due to inherited adenohypophyseal hypoplasia in the fetuses. PMID- 17873272 TI - Investigations of Escherichia coli O157 and some virulence genes in samples of meat and faeces from clinically healthy cattle in Turkey. PMID- 17873273 TI - Scrapie in goats. PMID- 17873274 TI - Control of bovine TB. PMID- 17873275 TI - Rabies vaccination. PMID- 17873276 TI - FeLV and FIV in a cat population. PMID- 17873278 TI - Secretion and assembly of type IV and VI collagens depend on glycosylation of hydroxylysines. AB - Most lysines in type IV and VI collagens are hydroxylated and glycosylated, but the functions of these unique galactosylhydroxylysyl and glucosylgalactosylhydroxylysyl residues are poorly understood. The formation of glycosylated hydroxylysines is catalyzed by multifunctional lysyl hydroxylase 3 (LH3) in vivo, and we have used LH3-manipulated mice and cells as models to study the function of these carbohydrates. These hydroxylysine-linked carbohydrates were shown recently to be indispensable for the formation of basement membranes (Ruotsalainen, H., Sipila, L., Vapola, M., Sormunen, R., Salo, A. M., Uitto, L., Mercer, D. K., Robins, S. P., Risteli, M., Aszodi, A., Fassler, R., and Myllyla, R. (2006) J. Cell Sci. 119, 625-635). Analysis of LH3 knock-out embryos and cells in this work indicated that loss of glycosylated hydroxylysines prevents the intracellular tetramerization of type VI collagen and leads to impaired secretion of type IV and VI collagens. Mice lacking the LH activity of LH3 produced slightly underglycosylated type IV and VI collagens with abnormal distribution. The altered distribution and aggregation of type VI collagen led to similar ultrastructural alterations in muscle to those detected in collagen VI knockout and some Ullrich congenital muscular dystrophy patients. Our results provide new information about the function of hydroxylysine-linked carbohydrates of collagens, indicating that they play an important role in the secretion, assembly, and distribution of highly glycosylated collagen types. PMID- 17873277 TI - Class A scavenger receptor-mediated macrophage adhesion requires coupling of calcium-independent phospholipase A(2) and 12/15-lipoxygenase to Rac and Cdc42 activation. AB - Class A scavenger receptors (SR-A) participate in multiple macrophage functions including adhesion to modified extracellular matrix proteins present in various inflammatory disorders such as atherosclerosis and diabetes. By mediating macrophage adhesion to modified proteins and increasing macrophage retention, SR A may contribute to the inflammatory process. Eicosanoids produced after phospholipase A(2) (PLA(2))-catalyzed release of arachidonic acid (AA) are important regulators of macrophage function and inflammatory responses. The potential roles of AA release and metabolism in SR-A-mediated macrophage adhesion were determined using macrophages adherent to modified protein. SR-A-dependent macrophage adhesion was abolished by selectively inhibiting calcium-independent PLA(2) (iPLA(2)) activity and absent in macrophages isolated from iPLA(2) beta(-/ ) mice. Our results further demonstrate that 12/15-lipoxygenase (12/15-LOX) derived, but not cyclooxygenase- or cytochrome P450-dependent epoxygenase-derived AA metabolites, are specifically required for SR-A-dependent adhesion. Because of their role in regulating actin polymerization and cell adhesion, Rac and Cdc42 activation were also examined and shown to be increased via an iPLA(2)- and LOX dependent pathway. Together, our results identify a novel role for iPLA(2) catalyzed AA release and its metabolism by 12/15-LOX in coupling SR-A-mediated macrophage adhesion to Rac and Cdc42 activation. PMID- 17873279 TI - Heat shock factor 1 attenuates 4-Hydroxynonenal-mediated apoptosis: critical role for heat shock protein 70 induction and stabilization of Bcl-XL. AB - Lipid peroxidation is a consequence of both normal physiology and oxidative stress that generates various reactive metabolites, a principal end product being 4-hydroxynonenal (HNE). As a diffusible electrophile, HNE reacts extensively with cellular nucleophiles. Consequently, HNE alters cellular signaling and activates the intrinsic apoptotic cascade. We have previously demonstrated that in addition to promoting apoptosis, HNE activates stress response pathways, including the antioxidant, endoplasmic reticulum stress, DNA damage, and heat shock responses. Here we demonstrate that activation of the heat shock response by HNE is dependent on the expression and nuclear translocation of heat shock factor 1 (HSF1), which promotes the expression of heat shock protein 40 (Hsp40) and Hsp70 1. Ectopic expression and immunoprecipitation of c-Myc-tagged Hsp70-1 indicates that HNE disrupts the inhibitory interaction between Hsp70-1 and HSF1, leading to the activation heat shock gene expression. Using siRNA to silence HSF1 expression, we observe that HSF1 is necessary for the induction of Hsp40 and Hsp70-1 by HNE, and the lack of Hsp expression is correlated with an increase in apoptosis. Nrf2, the transcription factor that mediates the antioxidant response, was also silenced using siRNA. Silencing Nrf2 also enhanced the cytotoxicity of HNE, but not as effectively as HSF1. Silencing HSF1 expression facilitates the activation of JNK pro-apoptotic signaling and selectively decreases expression of the anti-apoptotic Bcl-2 family member Bcl-X(L). Overexpression of Bcl-X(L) attenuates HNE-mediated apoptosis in HSF1-silenced cells. Overall, activation of HSF1 and stabilization of Bcl-X(L) mediate a protective response that may contribute significantly to the cellular biology of lipid peroxidation. PMID- 17873280 TI - The histone deacetylase HDAC4 connects neural activity to muscle transcriptional reprogramming. AB - Neural activity actively regulates muscle gene expression. This regulation is crucial for specifying muscle functionality and synaptic protein expression. How neural activity is relayed into nuclei and connected to the muscle transcriptional machinery, however, is not known. Here we identify the histone deacetylase HDAC4 as the critical linker connecting neural activity to muscle transcription. We found that HDAC4 is normally concentrated at the neuromuscular junction (NMJ), where nerve innervates muscle. Remarkably, reduced neural input by surgical denervation or neuromuscular diseases dissociates HDAC4 from the NMJ and dramatically induces its expression, leading to robust HDAC4 nuclear accumulation. We present evidence that nuclear accumulated HDAC4 is responsible for the coordinated induction of synaptic genes upon denervation. Inactivation of HDAC4 prevents denervation-induced synaptic acetyl-choline receptor (nAChR) and MUSK transcription whereas forced expression of HDAC4 mimics denervation and activates ectopic nAChR transcription throughout myofibers. We determined that HDAC4 executes activity-dependent transcription by regulating the Dach2-myogenin transcriptional cascade where inhibition of the repressor Dach2 by HDAC4 permits the induction of the transcription factor myogenin, which in turn activates synaptic gene expression. Our findings establish HDAC4 as a neural activity regulated deacetylase and a key signaling component that relays neural activity to the muscle transcriptional machinery. PMID- 17873281 TI - The confluence-dependent interaction of cytosolic phospholipase A2-alpha with annexin A1 regulates endothelial cell prostaglandin E2 generation. AB - The regulated generation of prostaglandins from endothelial cells is critical to vascular function. Here we identify a novel mechanism for the regulation of endothelial cell prostaglandin generation. Cytosolic phospholipase A(2)-alpha (cPLA(2)alpha) cleaves phospholipids in a Ca(2+)-dependent manner to yield free arachidonic acid and lysophospholipid. Arachidonic acid is then converted into prostaglandins by the action of cyclooxygenase enzymes and downstream synthases. By previously undefined mechanisms, nonconfluent endothelial cells generate greater levels of prostaglandins than confluent cells. Here we demonstrate that Ca(2+)-independent association of cPLA(2)alpha with the Golgi apparatus of confluent endothelial cells correlates with decreased prostaglandin synthesis. Golgi association blocks arachidonic acid release and prevents functional coupling between cPLA(2)alpha and COX-mediated prostaglandin synthesis. When inactivated at the Golgi apparatus of confluent endothelial cells, cPLA(2)alpha is associated with the phospholipid-binding protein annexin A1. Furthermore, the siRNA-mediated knockdown of endogenous annexin A1 significantly reverses the inhibitory effect of confluence on endothelial cell prostaglandin generation. Thus the confluence-dependent interaction of cPLA(2)alpha and annexin A1 at the Golgi acts as a novel molecular switch controlling cPLA(2)alpha activity and endothelial cell prostaglandin generation. PMID- 17873282 TI - Tyr687 dependent APP endocytosis and Abeta production. AB - The neurotoxic Abeta peptide is derived by proteolytic processing from the Alzheimer's amyloid precursor protein (APP), whose short cytoplasmic domain contains several phosphorylatable amino acids. The latter can be phosphorylated 'in vitro' and 'in vivo,' and in some cases phosphorylation appears to be associated with the disease condition. Using APP-GFP fusion proteins to monitor APP processing, the role of Tyr687 was addressed by mimicking its constitutive phosphorylation (Y687E) and dephosphorylation (Y687F). Contrasting effects on subcellular APP distribution were observed. Y687E-APP-GFP was targeted to the membrane but could not be detected in transferrin containing vesicular structures, and exhibited a concomitant and dramatic decrease in Abeta production. In contrast, Y687F-APP-GFP was endocytosed similarly to wild type APP, but was relatively favoured for beta-secretase cleavage. Overall, Tyr687 appears to be a critical residue determining APP targeting and processing via different pathways, including endocytosis and retrograde transport. Significantly, from a disease perspective, mimicking Tyr687 phosphorylation resulted in a hitherto undescribed inhibition of Abeta production. Our results provide novel insights into the role of direct APP phosphorylation on APP targeting, processing and Abeta production. PMID- 17873283 TI - Developmental regulation of SSeCKS expression in rat brain. AB - SSeCKS (src suppressed C kinase substrate) was identified as a PKC substrate/PKC binding protein, which plays a role in mitogenic regulatory activity and has a function in the control of cell signaling and cytoskeletal arrangement. Previous studies showed that expression of SSeCKS mRNA and protein levels were developmentally regulated in rat testis and the molecular might have some effects on the process of spermiogenesis. Here we carried out experiments to investigate the expression of SSeCKS in rat brain. Western blot analysis indicated that SSeCKS could be detected in the whole brain of developing rat embryos and reached its peak at 1 week after birth, while during mature period, its level was decreasing. Regional-distribution analysis showed that the expression pattern of SSeCKS in telencephalon, hippocampus and diencephalons was in accordance with the result from whole brain both in mRNA and protein level. However, in cerebellum, SSeCKS was almost in the same level, and in brainstem, the expression level was higher in 4-week-old rat brain than in 1-week-old one. Immunohistochemistry results showed SSeCKS was in diffused and granule-like distribution. Double immunofluorescence staining showed that it was expressed by some GFAP positive cells. All the results suggested that SSeCKS might affect brain development and further research is needed to have a good understanding of its function and mechanism. PMID- 17873284 TI - Src suppressed C kinase substrate regulates the lipopolysaccharide-induced TNF alpha biosynthesis in rat astrocytes. AB - The protein kinase C (PKC) is known to be a critical component in the signaling cascades that lead to astrocyte-activation. To further understand the mechanism of PKC signaling in astrocyte-activation, we investigated the effect of SSeCKS, a PKC substrate, on LPS-induced cytokine expression in astrocytes by RT-PCR and enzyme-linked immunosorbent assay. Exposure of the cells to LPS induced rapid translocation of SSeCKS to the perinuclear sides, ERK activation and pronounced TNF-alpha production, which can be inhibited by the PKC inhibitor Go6983. By using siRNA knockdown of SSeCKS expression, LPS-induced signaling events were partly inhibited, including ERK activation, inducible TNF-alpha biosynthesis and secretion. These results suggest that SSeCKS is involved in the LPS-induced TNF alpha expression in astrocytes mediated by PKC. PMID- 17873285 TI - Differential upregulation of heme oxygenase-1 (HSP32) in glial cells after oxidative stress and in demyelinating disorders. AB - Oxidative stress is implicated in the pathogenesis of demyelinating disorders and inflammatory responses. Heme oxygenase-1 (HO-1; HSP32) is a small heat shock protein (HSP) with enzymatic activity, which is inducible by oxidative stress. In this study we analyzed autopsy and biopsy brain samples of patients with multiple sclerosis (MS) and ADEM (acute disseminated leucoencephalomyelits) and spinal cord lesions of mouse EAE (experimental autoimmune encephalomyelitis), which was actively induced by immunization with myelin oligodendrocyte glycoprotein (MOG35 55) peptide, for the presence of HO-1. HO-1 was observed in glial cells during different stages: (1) during acute phases of mainly inflammatory diseases (EAE and ADEM) expression of HO-1 was prominent in microglia/macrophages and astrocytes, and upregulation correlated with inflammation, and (2) in early MS lesions HO-1 was expressed in oligodendrocytes. Furthermore, in glial cell cultures, we can show that upregulation of HO-1 in oligodendrocytes was paralleled by severe morphological damage. Oligodendrocytes underwent apoptotic cell death at a concentration of hydrogen peroxide (50-200 microM) which did not affect astrocytes or microglia. Using oligodendroglial OLN-93 cells, we demonstrate that oxidative stress led to mitochondrial impairment and the disorganization of the microtubule network. Zinc protoporphyrin, an inhibitor of HO-1, augmented the cytotoxic consequences of hydrogen peroxide in OLN-93 cells. Hence, the presence of HO-1 in EAE, ADEM, and MS points to the involvement of oxidative stress and a role of HO-1 in the pathogenesis of the diseases. The data suggest that stress-induced HO-1 initially plays a protective role, while its chronic upregulation, might contribute to oligodendroglial cell death rather than providing protection. PMID- 17873287 TI - Gabapentin completely attenuated the acute morphine induced c-Fos expression in the rat striatum. AB - The neuro-anatomical sites and molecular mechanism of action of gabapentin (GBP) morphine interaction to prevent and reverse morphine side effects as well as enhancement of the analgesic effect of morphine is not known. Therefore, we examined the combined effects of GBP-Morphine on acute morphine induced c-Fos expression in rat striatum. The combined effect of GBP-Morphine was examined by means of c-Fos immunohistochemistry. A single intraperitoneal injection (i.p.) of morphine (10 mg/kg), saline (control), co-injection of GBP (150 mg/kg) with morphine (10 mg/kg) was administered under anaesthesia. Ninety minutes after drugs administration the deeply anesthetized rats were perfused transcardially with 4% paraformaldehyde. Serial 40 mum thick sections of brain were cut and processed by immunohistochemistry to locate and quantify the sites and number of neurons with c-Fos immunoreactivity. Detection of c-Fos protein was performed using the peroxidase-antiperoxidase (PAP) detection protocol. Our present study demonstrated that, administration of GBP (150 mg/kg, i.p.) in combination with morphine (10 mg/kg, i.p.) significantly (p < 0.01) attenuated the acute morphine (10 mg/kg, i.p.) induced c-Fos expression in the rat striatum. Present results showed that GBP-morphine combination action prevented the acute morphine induced c-Fos expression in rat striatum. Moreover, this study provides first evidence of neuro-anatomical site and that GBP neutralized the morphine induced activation of rat striatum. PMID- 17873286 TI - Effects of aging, dietary restriction and glucocorticoid treatment on housekeeping gene expression in rat cortex and hippocampus-evaluation by real time RT-PCR. AB - Accurate normalization is the prerequisite for obtaining reliable results in the quantification of gene expression. Using TaqMan Real Time RT-PCR, we carried out an extensive evaluation of five most commonly used endogenous controls, gapdh, beta-actin, 18S rRNA, hprt and cypB, for their presumed stability of expression, in rat cortex and hippocampus, during aging, under dietary restriction and dexamethasone treatment. Valid reference genes (HKGs) were identified using GeNorm and NormFinder software packages and by direct comparison of Ct values. Analysis revealed gapdh and beta-actin as the most stable HKGs for all treatments analyzed, combined or separately, in the cortex, while in the hippocampus gapdh/hprt and beta-actin/hprt are the combination of choice for the single or combined effects of dietary restriction/dexamethasone, respectively. All treatments significantly influenced expression of 18S rRNA and cypB in both structures. In addition, we used gapdh and normalization factor, calculated by GeNorm, to compare the expression of alpha-syn in the cortex. Our results demonstrate the importance of the right choice of HKG and suggest the appropriate endogenous control to be used for TaqMan RT-PCR analysis of mRNA expression in rat cortex and hippocampus for selected experimental paradigms. PMID- 17873288 TI - Gene expression profiling of human gliomas reveals differences between GBM and LGA related to energy metabolism and notch signaling pathways. AB - Human malignant astrocytic tumors are the most common primary brain malignancies. Human gliomas are classified according to the extent of anaplasia or 'de differentiation' appearance. Although this type of histological classification is widely accepted, the extensive heterogeneity of astrocytic tumors has made their pathological classification rather difficult. New genome-scale high throughput technologies for gene expression profiling, such as DNA microarrays, are emerging as new tools to allow a more accurate identification and characterization of different tumor degrees by discovering new specific markers and pathways of each stage. Present work reports interesting results that might be useful to differentiate between tumor grades. Data presented here provides new evidences about the molecular basis underlying different tumor stages. In this sense, we identified key metabolic pathways, crucial for tumor progression, as being differentially regulated in different tumor stages. On the other hand, remarkable findings regarding Notch pathway are reported, as some members of this receptor family were found to be differentially expressed depending on the malignancy degree. Our results clearly point out important molecular differences between different tumor stages and suggest that more studies are needed to understand specific molecular events characteristic of each stage. These types of studies represent a first step to deepen into the tumor physiology, which may potentially help for better and a more precise diagnosis of gliomas. PMID- 17873289 TI - Expression of p27kip1 and Skp2 in the adult spinal cord following sciatic nerve injury. AB - Skp2 (S-phase-associated kinase protein-2) is involved in ubiquitination and proteasome-mediated degradation of p27kip1, which plays important roles in cell cycle regulation and neurogenesis in the developing central nervous system (CNS). But their distribution and function in the nervous system lesion and regeneration remains unclear. In this study, we examined expression and relationship of p27kip1 and Skp2 in adult rat spinal cord following sciatic nerve injury. It was illustrated that they localized mainly in neurons and astrocytes of spinal cord, and might also expressed in other glial cells according to the results of immunohistochemistry. Sciatic nerve crush and transection resulted in a significant up-regulation of Skp2 and a down-regulation of p27kip1 in spinal cord. Statistical analysis indicated negative correlation between the number of p27kip1 and Skp2 positive cells in the ventral horn following the sciatic nerve lesion. Immunoprecipitation further showed that they interacted with each other in the regenerating process. Thus, p27kip1 and Skp2 likely play an important role in spinal cord regeneration after peripheral nerve injury. PMID- 17873290 TI - Decoding of dopaminergic mesolimbic activity and depressive behavior. AB - Dopaminergic mesolimbic and mesocortical systems are involved in hedonia and motivation, two core symptoms of depression. However, their role in the pathophysiology of depression and their manipulation to treat depression has received little attention. Previously, we showed decreased limbic dopamine (DA) neurotransmission in an animal model of depression, Flinder sensitive line (FSL) rats. Here we describe a high correlation between phase-space algorithm of bursting-like activity of DA cells in the ventral tegmental area (VTA) and efficiency of DA release in the accumbens. This bursting-like activity of VTA DA cells of FSL rats is characterized by a low dimension complexity. Treatment with the antidepressant desipramine affected both the dimension complexity of cell firing in the VTA and rate of DA release in the accumbens, as well as alleviating depressive-like behavior. Our findings indicate the potential usefulness of monitoring limbic dopaminergic dynamics in combination with non-linear analysis. Decoding the functionality of the dopaminergic system may help in development of future antidepressant drugs. PMID- 17873291 TI - Opposing effects of proteasomes and lysosomes on LIFR: modulation by TNF. AB - The blood-brain barrier (BBB), a communicating interface for inflammation, transports cytokines through its endothelial cells. This study shows how tumor necrosis factor alpha (TNF) regulates the expression of the leukemia inhibitor factor receptor (LIFR) gp190 in RBE4 cells. The high expression of LIFR was rapidly downregulated by the proinflammatory agents lipopolysaccharide, TNF, and LIF. Downregulation by TNF affected LIFR endocytosis and lysosomal degradation, preceding decreased LIFR mRNA. Lysosomal inhibitors reversed the rapid disappearance of LIFR, whereas inhibition of the ubiquitin-proteasome pathway did not. Rather, blockade of proteasome activity, as well as inhibition of NFkappaB activation, reduced the basal expression of LIFR. Thus, NFkappaB activity and proteasome degradation of IkappaB stabilized LIFR and prevented its rapid lysosomal degradation. By a non-NFkappaB-mediated mechanism, TNF facilitated LIFR degradation and reduced LIFR activation indicated by pStat3. The novel opposite effects of proteasomes and lysosomes in controlling receptor expression shows the functional implications and interactions of circulating inflammatory cytokines in acutely modulating BBB activity. PMID- 17873292 TI - Mutant prion protein D202N associated with familial prion disease is retained in the endoplasmic reticulum and forms 'curly' intracellular aggregates. AB - Transmissible Spongiform Encephalopathies are fatal neurodegenerative disorders of humans and animals that are familial, sporadic, and infectious in nature. Familial disorders of humans include Gerstmann-Straussler-Scheinker disease (GSS), familial Creutzfeldt-Jakob disease (CJD), and fatal familial insomnia, and result from point mutations in the prion protein gene. Although neurotoxicity in familial cases is believed to result from a spontaneous change in conformation of mutant prion protein (PrP) to the pathogenic PrP-scrapie (PrPSc) form, emerging evidence indicates otherwise. We have investigated the processing and metabolism of mutant PrP D202N (PrP202N) in cell models to elucidate possible mechanisms of cytotoxicity. In this report, we demonstrate that PrP202N expressed in human neuroblastoma cells fails to achieve a mature conformation following synthesis and accumulates in the endoplasmic reticulum as 'curly' aggregates. In addition, PrP202N cells show increased sensitivity to free radicals, indicating that neuronal susceptibility to oxidative damage may account for the neurotoxicity observed in cases of GSS resulting from PrP D202N mutation. PMID- 17873293 TI - Evidence of postnatal neurogenesis in dorsal root ganglion: role of nitric oxide and neuronal restrictive silencer transcription factor. AB - The various mechanisms underlying postnatal neurogenesis from discrete CNS regions have emerged recently. However, little is known about postnatal neurogenesis in dorsal root ganglion (DRG). BrdU incorporation and subsequent immunostaining for BrdU, neural stem cell marker, nestin and neuronal marker, PGP 9.5 have provided evidence for postnatal neurogenesis in DRG. We further demonstrate, in vivo and in vitro, that nitric oxide (NO) regulates neural stem cells (nestin+) proliferation and, possibly, differentiation into neurons. Surprisingly, nerve growth factor (NGF) had no effect on nestin+ cells proliferation. Axotomy or NGF-deprivation of DRG neurons-satellite glia co culture increases NO production by neurons and treating with a NO synthase (NOS) inhibitor, N G-nitro-L-arginine methylester (L-NAME) in vitro or 7-nitroindazole (7NI) in vivo, causes a significant increase in nestin+ cell numbers. However, a soluble guanylyl cyclase (sGC) blocker, 1H-[1, 2, 4] oxadiazolo [4, 3-a] quinoxalin-1-one (ODQ) treatment of NGF-deprived DRG neurons-satellite glia co culture had no significant effect on nestin+ cell numbers. This implies NO regulates nestin+ cell proliferation independent of cGMP. We hypothesised that the neuronal-restrictive silencer transcription factor (NRSF, also termed REST), a master regulator of neuronal genes in non-neuronal cells, may be modulated by NO in satellite glia cultures. A NO donor, dimethyl-triamino-benzidine (DETA)-NO treatment of satellite glia cell cultures results in a significant increase in the NRSF/REST mRNA expression. The majority of cultured satellite glia cells express nestin, and also show increased levels of NOS, thus L-NAME treatment of these cultures causes a dramatic reduction in NRSF/REST mRNA. Overall these results suggest that NO inhibits neurogenesis in DRG and this is correlated with modulation of NRSF, a known modulator of differentiation. PMID- 17873294 TI - Polymorphism -238 G/A of tumor necrosis factor alpha gene promoter is a genetic risk factor for ischemic cerebrovascular disease. PMID- 17873295 TI - Wnt pathway anomalies in developing amygdalae of Turner syndrome-like mice. AB - Certain neurobehavioral deficiencies associated with Turner Syndrome have been attributed to brain volumetric abnormalities, particularly of the amygdala. Haplo insufficiency of a non-dosage compensated gene or genes on the X chromosome has been hypothesized to be the cause of the neuroanatomical defect. We examined gene expression levels of 6,628 genes in developing amygdalae of late-stage embryos of a mouse model for Turner Syndrome. In total, 161 genes show significant differences in expression level between TS and normal female amygdala. In silico pathway analysis of both X-linked and autosomal mis-regulated genes suggests that modulation of Wnt signaling is a critical factor in the normal growth and development of the amygdala. PMID- 17873296 TI - Smn depletion alters profilin II expression and leads to upregulation of the RhoA/ROCK pathway and defects in neuronal integrity. AB - Spinal muscular atrophy (SMA) is the most common genetic disease resulting in infant mortality due to severe loss of alpha-motor neurons. SMA is caused by mutations or deletions of the ubiquitously expressed survival motor neuron (SMN) gene. However, why alpha-motor neurons of SMA patients are specifically affected is not clear. We demonstrate here that Smn knockdown in PC12 cells alters the expression pattern of profilin II, resulting in an increase in the neuronal specific profilin IIa isoform. Moreover, the depletion of Smn, a known interacting partner of profilin IIa, further contributes to the increased profilin IIa availability. Altogether, this leads to an increased formation of ROCK/profilin IIa complex and an inappropriate activation of the RhoA/ROCK pathway, resulting in altered cytoskeletal integrity and a subsequent defect in neuritogenesis. This study represents the first description of a mechanism underlying SMA pathogenesis and highlights new targets for therapeutic intervention for this devastating disorder. PMID- 17873297 TI - Proteomic investigation of the ventral rat hippocampus links DRP-2 to escitalopram treatment resistance and SNAP to stress resilience in the chronic mild stress model of depression. AB - The development of depression as well as recovery from depression is most likely accompanied by a change in protein expression profiles. The purpose of the present study was to quantitatively investigate global protein expression differences independent of any hypothesis describing depression etiology and recovery. Thus two-dimensional differential in-gel electrophoresis was employed to compare the ventral hippocampal proteomes between different treatment groups in the chronic mild stress (CMS) model of depression. The CMS paradigm induces anhedonic behaviour, which is a major symptom of depression, by exposing rats to a series of mild stressors for 7 weeks, with antidepressant treatment during the last 4 weeks. In the CMS model, animals were split into six different groups at the end of treatment; unchallenged control escitalopram (n = 12), unchallenged control vehicle (n = 12), CMS vehicle (n = 12), CMS escitalopram responders (n = 11), CMS escitalopram non-responders (n = 13) and CMS resilient (stress resistant) (n = 12). Protein levels in the ventral rat hippocampus were compared between the groups to provide putative markers of anhedonia, escitalopram resistance, and stress resilience. Twenty-eight candidate protein spots were selected, of which 13 were successfully identified using tandem mass spectrometry. DRP-2 (dihydropyrimidinase-related protein-2) was a potential marker for escitalopram resistance, whereas alpha-SNAP and beta-SNAP were associated with stress resilience. Furthermore, several molecular chaperones and cytoskeleton organisers were identified as being differentially expressed. Our data indicate that neuronal adaptation is an essential element of depression etiology and recovery, suggesting the involvement of cellular plasticity in the underlying molecular mechanism. PMID- 17873298 TI - Heparin inhibits NF-kappaB activation and increases cell death in cerebral endothelial cells after oxygen-glucose deprivation. AB - Heparin is a classic anticoagulant that is commonly used in the treatment of acute ischemic stroke (AIS). Its use remains controversial, however, due to the risk of cerebral hemorrhagic transformation. In addition to anticoagulant effects, diverse effects on transcription factors can be caused by heparin. Among the transcription factors potentially affected is nuclear factor kappa B (NF kappaB), a protein that is reportedly related to the survival of cerebral endothelial cells. We investigated the effect of heparin on NF-kappaB activation and cell death following oxygen-glucose deprivation (OGD), an experimental model of AIS. We subjected bEnd.3 cells from a murine cerebral microvascular endothelial cell line to OGD. We examined the effect of heparin on OGD-induced NF kappaB activation and its mechanism of action, using electrophoretic mobility shift assays, reporter gene analysis, real-time RT-PCR, Western blot analysis, and confocal microscopy. We also measured the effect of heparin on OGD-induced cell death using an MTT assay. Heparin inhibited both tumor necrosis factor alpha and OGD-induced NF-kappaB activation. Heparin was taken up by endocytosis and then entered the nucleus. Heparin did not affect the nuclear translocation of NF kappaB, but instead inhibited the DNA binding of NF-kappaB in the nucleus. Cells were more susceptible to OGD-induced cell death after heparin treatment. Besides producing an anticoagulation effect, heparin also inhibits NF-kappaB activation, resulting in increased susceptibility to OGD-induced cell death. This effect may be responsible for hemorrhagic transformation in patients following heparin treatment for AIS. PMID- 17873299 TI - CYP1A1 and GSTM1/T1 genetic variation in predicting risk for cerebral infarction. AB - Cytochrome P450 1A1 (CYP1A1) is involved in the production of arachidonic acid derived vasoactive substance. We hypothesized that CYP1A1 polymorphism might be related to pathological conditions associated with cerebral infarction (CI). We investigated the effect of genetic polymorphism in the 3'-flanking region (T6235C) of CYP1A1 gene in 353 patients with CI and 376 controls. The distributions of T6235C CYP1A1 genotypes in patients with (TT: 36.0%; TC/CT: 64.0%; n = 353) and without CI (TT: 44.7%; TC/CT: 55.3%; n = 376) indicate that the C allele is associated with CI (P = 0.017, odds ratio (O.R.) = 1.44; 95% confidence interval (C. I.) = 1.07-1.94). Furthermore, we examined whether the glutathione S-transferase (GST) gene, which is one of detoxification enzyme, influence the risk of CI. GST M1 null genotype increased the relative risk for the CI in the subjects with the CYP1A1 C allele (P = 0.015, O.R. = 1.47; C. I. = 1.08-2.00). We conclude that T6235C CYP1A1 polymorphism is a risk factor for the development of CI and suggest that GST polymorphism contribute to the odds of CI. PMID- 17873300 TI - Expression of telomerase reverse transcriptase in adult goldfish retina. AB - Telomerase, a specialized reverse transcriptase that maintains telomere during cell division, is commonly associated with cell proliferation. Increasing evidence suggests that telomerase may bear functions other than telomere elongation. We investigated whether telomerase is expressed in the continuously growing goldfish retina. Telomeric repeat amplification protocol (TRAP) assay reveals telomerase activity in goldfish retina. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot show that telomerase catalytic subunit (TERT) is expressed at both mRNA and protein levels. Localization of TERT by immunohistochemistry indicates prominent expression of TERT in the outer nuclear layer, the inner nuclear layer, and, in a small population of cells, in the ganglion cell layer. Coexpression of TERT with proliferative cell nuclear antigen (PCNA) immunoreactivity is found in rod progenitor cells. These results suggest the role of telomerase in vertebrate central nervous system (CNS) other than telomere maintenance, such as regulation of cell cycle progression and maintenance of retinal cell phenotypes. PMID- 17873301 TI - Erythropoietin therapy and cancer related anaemia: updated Swedish recommendations. AB - Due to concerns related to treatment with erythropoietin (EPO) and possible negative effects on tumour control, a workshop was organised by the Medical Products Agency of Sweden with the aim to revise national treatment guidelines if needed. In patients with solid tumours, conflicting results have been reported with respect to tumour control and survival. Until further notice it is therefore recommended that EPO should be used restrictively in the treatment of patients with cancer and that the anticipated improvement in quality of life should be evaluated against potential risks. PMID- 17873302 TI - Current perspectives in the treatment of advanced prostate cancer. AB - Prostate cancer (PC) continues to be an important world health problem for men. Patients with locally confined PC are treated with either radiotherapy or surgery. However, treatment of more advanced stages of the disease is problematic. Initially, androgen deprivation offers a period of clinical stability, which is however invariably followed by progression to non responsiveness to hormonal manipulation. Current management of patients with androgen-independent prostate cancer (AIPC) displays modest response rates and achieves only short-term benefit. Recently, knowledge in the complex pathophysiology of advanced PC has led to the identification of mechanisms and target molecules permitting the introduction of new therapies. Consequently, many investigational treatments are ongoing for AIPC in Phase-II and Phase-III trials aiming at the combination of chemotherapeutic regimens along with immunotherapy targeting PC-associated antigens. Other attractive options are gene therapy, as well as the targeting of survival signaling, differentiation, and apoptosis of the malignant PC cells. Further treatment modalities are directed against the tumor microenvironment, bone metastasis, or both. Collectively, the aforementioned efforts introduce a new era in the management of advanced PC. Novel pharmaceutical compounds and innovative approaches, integrated into the concept of individualized therapy will hopefully, during the next decade, improve the outcome and survival for hundreds of thousands of men worldwide. PMID- 17873303 TI - Liver embolizations in oncology. A review. Part II. Arterial radioembolizations, portal venous embolizations, experimental arterial embolization procedures. AB - Arterial embolization of the liver may temporarily retard the growth of its primary and secondary tumors which are both mainly nourished arterially. Addition of radioisotopes, mostly (131)I or (90)Y, results in radioembolizations which predominantly act by radiation and less by ischemia. They may therefore be utilized in the absence of portal venous flow when conventional embolization is hazardous. (131)I-oily radioembolization seems to prolong short-term survival in such patients with unresectable hepatocellular cancers, and to improve the prognosis after resection of hepatocellular cancer. The procedure does however not palliate better than "cold" chemoembolization in patients with preserved portal flow, except for having milder side effects. Embolization with (90)Y coupled microspheres may shrink primary and secondary liver tumors but has so far unproven effects on survival. Embolization of portal venous branches gives compensatory hypertrophy of the non-embolized liver and can increase the volume of the future remnant liver before resection. This diminishes the risk for postoperative liver failure after extensive resection and/or in the presence of chronic liver disease, and permits wider surgical indications. Tumor growth may however be accelerated, and the hypertrophy is inhibited by severe liver parenchymal disease in which situation the method would be most needed. Experimental use of liver arterial embolizations includes combined arterial and portal embolizations, i.e. "chemical hepatectomy," arterial embolizations before external radiotherapy, administration of boron for neutron capture therapy, immunoembolizations, and future gene therapy. PMID- 17873304 TI - Cancer during pregnancy: 10-year experience at a regional cancer reference center in Mexico. AB - INTRODUCTION: Cancer during pregnancy is uncommon. However, recent trends in the prolongation of the childbearing age have made cancer-associated pregnancies more frequent. The objective of our study was to describe the frequency, types of cancer, and treatment with this association in our institution. MATERIAL AND METHODS: The clinical records of 36 patients, who presented to a regional reference center in Mexico over 10 years were reviewed collecting demographics, pregnancy characteristics and outcomes, type of cancer, clinical stage, treatment, and oncological outcome. RESULTS: The following tumors were observed: Uterine cervix (20), breast (7), ovary (3), non-Hodgkin Lymphoma (2), and other malignancies (4). The mean age of the patients was 30 (range 20-39) years. Mean follow up was 17.8 (range 1-74) months. The pregnancies were synchronous in 23 cases and 13 were diagnosed in the following 12 months after birth. Mean gestational age of the product was of 37.4 weeks, resulting in 15 deliveries with healthy products, four abortions, and four deaths. The majority of patients had advanced clinical stages. Overall survival was 36.4%. DISCUSSION: Cancer during pregnancy appears to have a worse outcome when compared to the results reported in the literature of non-pregnant women with the same conditions. This may be related to the advanced clinical stages we found. Cancer during pregnancy requires specialized attention to improve both fetal and maternal outcomes. PMID- 17873305 TI - Intensive weekly chemotherapy with docetaxel, epirubicin and carboplatin with G CSF support in patients with advanced gastric cancer: a Hellenic Cooperative Oncology Group (HeCOG) phase II study. AB - Chemotherapy is an established modality in the management of patients with advanced gastric cancer but the optimal regimen has not been defined yet. Platinum and the anthracyclines and more recently docetaxel have shown activity in this tumor. The primary objective of this phase II study was to assess the efficacy and safety of an intensified regimen of weekly docetaxel/epirubicin/carboplatin (DECb) with growth factor support in previously untreated patients with advanced gastric cancer. A total of 72 patients with measurable disease received docetaxel at a dose of 30 mg/m2, epirubicin at a dose of 30 mg/m2 and carboplatin to a target area under the curve (AUC) of 2, every week for 6 consecutive weeks followed by 2 weeks' rest, with filgrastim support. Analysis was performed on an intention to treat basis. The main toxicity was hematologic with grade 3/4 neutropenia occurring in 35% of the patients. Other grade 3/4 toxicities included anemia (7%), thrombocytopenia (14%) and leucopenia (26%). The relative dose intensity of docetaxel and epirubicin was 62%. The overall response rate was 21%, the median time to tumor progression was 4.1 months and the median survival 7.3 months. Intensified weekly treatment with DECb has modest activity in the treatment of advanced gastric cancer. Myelotoxicity limits adequate drug delivery. PMID- 17873306 TI - Pentoxifylline and alpha-tocopherol in prevention of radiation-induced lung toxicity in patients with lung cancer. AB - Combined use of pentoxifylline and vitamin E is reported to reduce radiation induced toxicity in normal tissues at molecular level. We plan to evaluate the role of combined use of pentoxifylline (PTX) and alpha-tocopherol (vitamin E; Vit E) for minimizing radiation-induced lung toxicity. A total of 91 lung cancer patients were randomized. Among them, 44 received PTX (400 mg three times a day orally and Vit E 300 mg twice a day orally during the entire period of radiotherapy. PTX and Vit E were further administered at doses of 400 mg once a day and 300 mg once a day, respectively for 3 months after radiotherapy. A total of 47 patients were assigned as a control group. Radiation related acute and late toxicities are evaluated by radiation RTOG/EORTC toxicity scale. Median age was 59 (range, 41-75). Median follow-up was 13 months (range, 3-28 months). Radiation induced lung toxicity was more frequent in control group for all phases than in pentoxifylline and alpha-tocopherol group (acute phase, P = 0.042, subacute phase P = 0.0001, late phase P = 0.256). PTX and Vit E combination might be considered especially in patients with lung cancer who receive concurrent chemo radiotherapy, or have a poor respiratory function tests. PMID- 17873307 TI - Clinical stage-depending decrease of NK cell activity in multiple myeloma patients. AB - Natural killer cells, as an important subpopulation of cells of the innate immune system have an essential role in defense of the rise and spread of malignancy. These cells have a CD3-CD16 + CD56+ phenotype and they are functionally defined by their ability to lyses tumor cells. We here show that decrease of NK cell activity was significantly associated with advanced clinical stage, increased lactate dehydrogenase (LDH), percentage infiltration of bone marrow with plasma cells, and beta-2 microglobulin. The patients with higher NK cell activity at presentation after receiving VAD protocol have better cumulative survival in comparison with those with low NK cell activity. PMID- 17873308 TI - Evaluation of beta globin mRNA as an early marker of haemoglobin response to epoetin treatment. AB - Approximately 60% of anaemic cancer patients respond to epoetin treatment. An early marker of response would be valuable in order to avoid ineffective treatment. We have previously shown that beta globin mRNA increases rapidly after epoetin beta treatment of healthy controls. In the present study we have evaluated whether a change of this marker during the first 2 weeks of epoetin treatment could predict later Hb response in anaemic cancer patients. Twenty cancer patients with Hb <11 g/dl received epoetin beta (NeoRecormon) 10,000 IU three times weekly during 6 weeks. Hb, reticulocytes and beta-globin mRNA were followed. The latter was measured quantitatively using PCR via the 5' nuclease assay. Eleven patients responded with a Hb increase of >1 g/dl, nine were nonresponders. All responders increased in beta-globin mRNA within 2 weeks, mean 7.7 x base-line. With a cut-off of an increase of 3 x base-line value, we obtained a specificity of 45% and a sensitivity of 91% for the prediction of a later increase of Hb >1 g/dl. With a cut-off of 4x base-line, the specificity increased to 66%, but the sensitivity decreased to 82%. Beta globin mRNA increases before Hb in all responding patients. However, some non-responding patients also show an increase, and there is a trade-off between specificity and sensitivity as the cut-off level is set at different levels. Compared to reticulocyte count, beta-globin mRNA is more reliable in the individual patient, but the clinical usefulness of the assay needs to be evaluated in further studies. PMID- 17873309 TI - Anaemia in patients with cancer: role of inflammatory activity on iron metabolism and severity of anaemia. AB - Hepcidin has been proposed as an important factor in the pathogenesis of the anaemia of chronic disease (ACD). The aim of this study was to assess the relationship between anaemia and inflammatory activity in patients with solid tumours. Patients were classified as having iron deficiency anaemia (IDA) (hypoferremia and hypoferretinemia), ACD (hypoferremia, normal or increased serum ferritin) and anaemia related to cancer (ARC) (no abnormalities in iron status). Serum pro-hepcidin, IL-6, C-reactive protein (CRP) and iron status parameters were measured using commercial kits. CRP and IL-6 levels were significantly higher in patients with ACD when compared to IDA, ARC and non anaemic patients (P < 0.005). Serum pro-hepcidin levels were not different among all studied groups (P = 0.138). A negative correlation was observed between haemoglobin and serum ferritin, CRP and IL-6 levels only in group of ACD. Serum pro-hepcidin concentrations were not correlated with degree of anaemia or iron metabolism parameters. According to our results the inflammatory activity represented by high levels of IL-6 and CRP are involved in the pathogenesis of ACD, probably due to the action of inflammation on iron metabolism, but not in ARC. It was not possible to demonstrate a significant effect of pro-hepcidin on the anaemia in cancer patients. PMID- 17873310 TI - Endocrine pancreatic tumors with glucagon hypersecretion: a retrospective study of 23 cases during 20 years. AB - BACKGROUND: Glucagon-secreting endocrine pancreatic tumor is a rare disease, hence controlled studies on clinical management are lacking. In an attempt to assess the efficacy of diagnostic and therapeutic measures in patients with glucagonoma, a retrospective study was performed using the archives of a tertiary care center. PATIENTS AND METHODS: Records from 340 patients with endocrine pancreatic tumors were reassessed and 23 patients with malignant endocrine pancreatic tumor and elevated plasma glucagon levels were identified. RESULTS: About 7% of patients with histologically verified tumors fullfilled our criteria for glucagonoma. Only 22% of these patients had developed diabetes prior to the diagnosis of glucagonoma. Seventy eight percent had metastatic disease to the liver at diagnosis. Necrolytic migratory erythema was diagnosed or clinically suspected in 52%. Somatostatin receptor scintigraphy was positive in 95%. Nineteen patients received chemotherapy at some point, in 18 cases streptozotocin and 5 FU. With this treatment, objective radiological responses were seen in 50% of evaluable patients. Other treatment modalities used were interferon, somatostatin analogs, hepatic artery embolization, radio-frequency ablation of liver metastases, and radiolabeled somatostatin analogs. During the study period, 11 patients died at a median of 80 months from diagnosis whereas 11 patients are still alive after a median follow up of 52 months. One patient was lost to follow up. CONCLUSIONS: Glucagonomas represent 7% of our comprehensive referral material of endocrine pancreatic tumors. Necrolytic migratory erythema was a common finding (52%) and diabetes less frequent at presentation than previously reported. Tumors were positive on somatostatin receptor scintigraphy and objective responses were seen to chemotherapy. PMID- 17873311 TI - C-reactive protein as an acute phase protein in cancer patients. AB - The aim of our study was to determine the rate of elevation of c-reactive protein in cancer patients and to evaluate its correlation with other acute phase proteins. A total of 104 patients with various types of cancer who admitted clinic were included in our study. Serum levels of c-reactive protein, lactate dehydrogenase, ferritin, haptoglobin, plasma fibrinogen levels and erythyrocyte sedimentation rate were measured. The serum levels of c-reactive protein was found to be increased in 74% of cancer patients, with 81.3% and 64.4% in metastatic and non-metastatic group, respectively. Our study showed that c reactive protein and fibrinogen demonstrated better characteristics than other acute phase proteins to differentiate between cancer patients and healthy individuals and also to differentiate between healthy individuals and patients with infection. C-reactive protein, ferritin, fibrinogen, erythrocyte sedimentation rate, and haptoglobin showed similar characteristics to differentiate metastatic and non-metastatic cancer patients whereas, LDH demonstrated the lowest performance. C-reactive protein was not found to be superior to other acute phase proteins in the differential diagnosis of cancer and infection and in differentiating early stage disease from advanced stage. PMID- 17873312 TI - Aberrant expression of Eag1 potassium channels in gastric cancer patients and cell lines. AB - Recently, an interesting relationship between potassium channels and cancer has evolved. The aim of this study is to investigate expression of Eag1 potassium channel in gastric cancer and its role in cancer cells growth. The expression of Eag1 for gasric cancer patients and cell lines as well as gastric adenoma was investigated by immunohistochemistry and reverse transcription polymerase chain reaction. In addition, imipramine was used to identify the involvement of Eag1 in the growth of SGC-7901 and BGC-823 cells. Frequency of positive expression of Eag1 protein was 70.5% (67/95) and Eag1 mRNA was 68.2% (15/22) in gastric cancer primary tissues. Eag1 mRNA was positively expressed in two gastric cell lines. Eag1 protein and mRNA were negatively expressed in paired non-cancerous matched tissues and 5 cases of adenoma tissues. The expression level of Eag1 protein was associated with lymph node metastasis (P = 0.049) and stage (P = 0.039), but had no correlation with sex, age, differentiation grades, and other organs metastases. Imipramine significantly inhibited the proliferation of SGC-7901 and BGC-823 cells at 12 h and 24 h detected by cells number counting and MTT assay (P < 0.01). The study indicates Eag1 is aberrantly expressed in gastric cancer tissues and cell lines and associated with cancer lymph node metastasis and stage and play an important role in the proliferation of gastric cancer cells. PMID- 17873313 TI - An extraordinary case in whom gastrointestinal stromal tumor and low-grade malignant lymphoma are seen together in the stomach. AB - INTRODUCTION: Gastrointestinal system (GIS) is the most common site of involvement of all primary extranodal lymphomas. Gastric lymphoma constitutes 3 6% of all primary stomach malignancies. Stomach is also the commonest site of involvement of gastrointestinal stromal tumors (GIST). We would like to report these rare synchronous tumors in the same patient. CASE: A 68-year-old male was admitted to the internal medicine clinics with the complaints of abdominal distension. Physical examination was normal. On abdominal computed tomography a 12 x 14 x 22 cm sized giant tumoral mass was detected in left hypochondrium. A total gastrectomy was performed. Two distinct neoplasms were detected; one of which was located in the posterior wall of the stomach with the size of 24 x 16 x 13 cm, and the other one was localized in the fundus of the stomach and its size was 6 x 5 x 2 cm. Pathological evaluation revealed the diagnosis of GIST at the posterior wall and low-grade malignant lymphoma from the mass localized in the fundus of the stomach. DISCUSSION: Two primary tumors are not seen so often together in the stomach. Adenocarcinoma and associated tumors including gastric lymphoma (especially MALT lymphoma), carcinoid, leiomyosarcoma and rhabdomyosarcoma constitute most of the reported series. Rarely adenocarcinoma and associated GIST cases were reported. It is important to report concurrent gastric lymphoma and GIST case since it is extremely rare in the English literature. PMID- 17873314 TI - Relapse of preB-ALL after rituximab treatment for chronic graft versus host disease: implications for its use? AB - In acute lymphatic leukaemia (ALL) treated with allogenic stem cell transplantation limited chronic graft versus host disease (cGVHD) is associated with a higher 5 year disease free survival. This indicates an important graft versus-leukemia (GVL) effect, although this effect is less pronounced in ALL than in other malignancies. B-cell depletion using Rituximab is a treatment option in therapy refractory cGVHD that has been used successfully in a limited number of patients with an approximate response rate of 70%. Only two ALL patients with cGVHD treated with Rituximab are found in the literature. Here we describe a pre B-ALL patient with therapy refractory cGVHD who relapsed only one month after receiving Rituximab therapy for cGVHD. The Rituximab therapy may have triggered the relapse by targeting the shared cGVHD and GVL mechanisms, diminishing the GVL effect. Although no definite conclusions can be drawn from one case this might have implications for the use of Rituximab in cGVHD in ALL patients. PMID- 17873315 TI - Intravenous gammaglobulin-induced chronic renal failure in a patient with multiple myeloma. AB - Although generally well tolerated there have been a number of reports of acute deterioration in renal function with the use of intravenous immune globulin (IVIG). It is of generally limited duration and is self-limiting. We for the first time have described a patient with multiple myeloma and normal renal function who developed chronic renal failure shortly after IVIG treatment in a patient with no pre-existing renal disease. We would therefore recommend the cautious use of IVIG in patients with normal renal function or with pre-existing renal disease. Renal function should also be assessed both prior to and after application of IVIG. PMID- 17873316 TI - Letter to editor. Re: "Effect of concomitant use of pentoxifylline (PTX) and alpha-tocopherol with radiotherapy on the clinical outcome of patients with stage IIIB non-small cell lung cancer". PMID- 17873317 TI - The interplay of insulin resistance and beta-cell dysfunction involves the development of type 2 diabetes in Chinese obeses. AB - Type 2 diabetes mellitus (T2DM) is a heterogeneous disorder characterized by defects in insulin secretion and action and obesity plays an important role in the deterioration of glucose metabolism. In the present study we evaluated the degree of insulin resistance and first-phase insulin secretion of beta-cell in obese subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM in Chinese. A total of 220 subjects underwent standard 75 g oral glucose tolerance test (OGTT) and insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT). Insulin sensitivity index (S I) was assessed by the reduced sample number (n = 12) of Bergman's minimal model method with FSIGT. Insulin secretion capacities were determined by the insulinogenic index (I 30 min - I 0 min)/(G 30 min - G 0 min) in OGTT and the acute insulin response to glucose (AIR) in FSIGT. The disposition index (DI), the product of AIR and S I was used to determine whether AIR was adequate to compensate for insulin resistance. The S I in healthy lean control group was significantly higher than that in NGT, IGT, and T2DM group, but there was no significant difference among NGT, IGT, and T2DM group. The AIR in NGT group was significantly greater than that in control group, but then it was progressively decreased in IGT and T2DM group. The value of DI in control group was significantly higher than that in those three abnormal groups, and was decreased from NGT to IGT and T2DM group with significant difference. It indicates that obese subjects with different glucose tolerances have a similar degree of insulin resistance but differ in insulin secretion in Chinese Han population. PMID- 17873318 TI - Unchanged asymmetric dimethylarginine levels in non-diabetic, premenopausal obese women who have common risk factors for cardiovascular disease. AB - This study was performed to test whether plasma asymmetric dimethylarginine (ADMA) concentrations are related to obesity and obesity complications including decrement in insulin sensitivity and adiponectin levels, dyslipidemia and low grade inflammation. Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) concentrations were analyzed by HPLC in 17 overweight (BMI > or = 25 kg/m2) and 40 obese (BMI > or = 30 kg/m2) premenopausal women. Age matched healthy women were studied as controls. Obesity did not give rise to a significant change in circulating ADMA levels but reduced in SDMA levels. As compared with control subjects (0.441 +/- 0.102 microM), ADMA values in overweight and obese subjects were found to be as 0.412 +/- 0.102 and 0.436 +/- 0.093, respectively. No Pearson's association of ADMA with relevant risk variables for cardiovascular disease, including blood pressure, insulin sensitivity, inflammatory markers, lipid and adiponectin levels. However, in linear regression analysis, BMI, diastolic blood pressure, glucose, insulin, and IL-8 emerged as significant predictors of ADMA. In spite of obese women have elevated hs-CRP, triglyceride levels and decreased insulin sensitivity, adiponectin and HDL-cholesterol levels, all of which is closely linked risk factors for cardiovascular disease, circulating ADMA levels remained unchanged in obese individuals as compared with controls. PMID- 17873319 TI - Differential effects of cetuximab and AEE 788 on epidermal growth factor receptor (EGF-R) and vascular endothelial growth factor receptor (VEGF-R) in thyroid cancer cell lines. AB - This study evaluated the role of EGF and the effects of EGF-targeting drugs (Cetuximab, AEE 788) on growth, apoptosis, and autocrine VEGF-secretion of thyroid cancer (TC) cells. Autocrine activation of the epidermal growth factor receptor (EGF-R) is commonly regarded to contribute to the malignant phenotype of TC cells and may therefore represent a rational therapeutic target. Out of a number of TC cell lines two anaplastic (Hth74, C643), one follicular (FTC133), and one papillary thyroid cancer cell line (TPC1) were analyzed in depth for VEGF R-and EGF-R-expression, basal and EGF-stimulated (1-100 ng/ml) VEGF protein secretion and proliferation. Subsequently the antiprolifereative and antiangiogenic effect of cetuximab (Erbitux), a monoclonal antibody that blocks the EGF-R and AEE 788, a novel dual-kinase inhibitor of EGF-R and VEGF-R were assessed, and the downstream EGF-R signal transduction was analyzed by means of detecting phosphorylated pEGF-R, pVEGF-R, pAkt, and p-MAPK. EGF stimulated VEGF mRNA expression and protein secretion in all TC cell lines. The EGF-R antagonist Cetuximab consistently decreased VEGF secretion in all TC cell lines (min. 15%, n.s. in C643 cells and max. 90% in Hth74 cells, P < 0.05), but did not affect tumor cell proliferation in vitro. In contrast, the EGF-R- and VEGF-R-kinase inhibitor AEE 788 not only reduced VEGF secretion (min. 55%, P < 0.05 in C643 and max. 75%, P < 0.05, in FTC133), but also exhibited a dose-dependent inhibition of tumor cell proliferation (min. 75%, P < 0.05 in C643 and max. 95%, P < 0.05 in Hth74) and was a potent inductor of apoptosis in two of four TC cell lines. These effects were always accompanied by reduced levels of pEGF-R, pVEGF-R, pAkt, and pMAPK. Although inhibition of the EGF-receptor by Cetuximab potently disrupts autocrine secretion of VEGF, only the concurrent inhibition of the VEGF- and EGF receptor, e.g., by AEE 788 induces reduced proliferation and apoptosis in vitro. This suggests a particular rationale for the use of tyrosine kinase inhibitors with dual modes of action such as AEE 788 in thyroid cancer. PMID- 17873320 TI - Intercellular adhesion molecule 1 gene polymorphisms do not contribute to Graves' disease in Chinese patients. AB - OBJECTIVE: In order to study the association of G241R polymorphism of ICAM-1 gene with an earlier onset of Graves' disease (GD) and the susceptibility of K469E polymorphism to Graves' ophthalmopathy (GO) in Chinese population. STUDY DESIGN: A case-control and replication study was performed in 212 GD patients and 204 healthy subjects to analyze the genotypes. Furthermore the distribution of ICAM-1 genotypes was investigated in subgroups of patients with GD according to the onset age and the ophthalmopathy. RESULTS: No G241R polymorphism of ICAM-1 gene was detected in Chinese. No significant differences of allele and genotype frequencies regarding K469E polymorphism were found between GD patients and healthy controls (chi2 = 0.092, P = 0.762; chi2 = 1.089, P = 0.580). In addition, the genotype-phenotype correlation was not identified either. CONCLUSIONS: We found no association of G241R and K469E polymorphisms of the ICAM-1gene with the development of GD in a Chinese population. However, we could not rule out possible contributions of other polymorphisms of the ICAM-1gene to the pathogenesis of GD. Therefore, further studies are needed to elucidate the role of ICAM-1gene in Graves' disease in different population. PMID- 17873321 TI - Prolactin-releasing Peptide (PrRP) increases prolactin responses to TRH in vitro and in vivo. AB - The Prolactin-releasing Peptide (PrRP) is a 31-aminoacid peptide produced and secreted from the hypothalamus, and postulated to promote the prolactin release from the pituitary. However, the action of PrRP remain controversial, since it was described to have potency comparable enough to TRH, although there are many evidences that PrRP is less potent than TRH. Here we have studied the effects of PrRP alone or in combination with TRH in the prolactin levels of rat pituitary primary cell cultures in vitro and also in vivo prolactin responses in randomly cycling and estrogens-treated female rats. PrRP itself increased prolactin levels in vitro and in vivo, although in a magnitude several times lower than TRH. In vivo PrRP promotes an atypical non-peaking progressive and maintained prolactin increase. On the other hand, PrRP markedly increased the prolactin responses to TRH in vitro (10-30 fold increase) and in vivo (up to three-fold increase). In addition, FGF-2 and EGF, two important growth factors present in the pituitary, reduced the PrRP-induced prolactin increase in vitro. Taken together our results suggest that PrRP released from the hypothalamus may be relevant to modulate the circulating prolactin levels in the rat. PMID- 17873322 TI - Regulation of circulating leptin and its soluble receptor during pubertal development in the male rhesus monkey (Macaca mulatta). AB - In humans, circulating leptin levels are low in early childhood and rise until puberty, whereas the reverse occurs for the soluble leptin receptor (sOB-R). In women, leptin remains high and sOB-R remains low, but in men leptin declines after adolescence and sOB-R increases. These observations suggest that leptin may regulate the production of sOB-R, and that the increased testosterone in adolescent boys may be responsible for the gender differences in leptin and sOB R. To test this hypothesis, leptin was administered continuously to agonadal juvenile male monkeys for 16 days. No change in sOB-R was observed. Intact juvenile male monkeys were given pulsatile doses of gonadotropins for a period of 7 weeks to induce precocious puberty and assess the effect on plasma testosterone, leptin, and sOB-R. By 4 weeks testosterone had reached adult levels. No changes were observed in leptin, but by week 4, sOB-R was higher than pretreatment values and remained higher at week 7. These data suggest that leptin may not play a significant role in regulating the production of sOB-R and that gender differences in sOB-R in humans may be driven by the increased production of testosterone at puberty in males. PMID- 17873323 TI - Role of glucocorticoids and glucocorticoid receptor in priming of macrophages caused by glucocorticoid receptor blockade. AB - We previously reported that glucocorticoid receptor (GR) blockade (injected with GR antagonist RU486) primed the host responses to lipopolysaccharide. Since decrease of GR and elevated glucocorticoids (GCs) have been always reported as parallel responses, we hypothesize that both GCs and GR play important roles in GR blockade induced priming. We first confirm that the production of nitric oxide (NO), superoxide (O2-), and PKCalpha expression are all increased in peritoneal macrophages from GR blockade rats, indicating that macrophages are primed by GR blockade. Furthermore, using unilateral adrenalectomy rats, we find that the elevated GCs caused by a feedback mechanism following GR blockade may be involved in the process of priming. In vitro experiments in RAW264.7 cells show the inhibitory effect of GCs on NO production, which can be thoroughly blocked by RU486, indicating the increase of NO production in GR blockade rats is due to the elimination of GCs's anti-inflammatory function. In contrast, 10(-7) M corticosterone induces significant increases in O2- release, PKCalpha expression and phosphorylation, which cannot be reversed by RU486, demonstrating a previously unrecognized pro-inflammatory role of GCs in enhancing PM activation through a GR-independent pathway. The effect of GCs on PKCalpha expression even exists in GR deficient COS-7 cells as well as in GR knock-down RAW264.7 cells. In conclusion, both GR impairment and elevation of GCs are involved in the priming of macrophages caused by GR blockade. The findings of the divergent roles of GCs in modulation of inflammation may change therapeutic strategy for inflammatory diseases with GCs. PMID- 17873324 TI - The G1422A variant of the cannabinoid receptor gene (CNR1) is associated with abdominal adiposity in obese men. AB - Since recent data suggest that the endocannabinoid system controls food intake through central, and lipogenesis via peripheral CB1 receptors, we hypothesized that genetic variation at the cannabinoid receptor-1 (CNR1) locus could have an effect on adiposity. We investigated, whether a specific CNR1 G1422A genotype is associated with anthropometric markers of obesity and fat distribution in adult obese individuals. A total of 1,064 obese subjects (BMI > or = 30 kg/m2) without diabetes, impaired glucose tolerance or other endocrine diseases and 251 healthy control persons were genotyped for the G1422A variant (rs1049353) with a TaqMan assay. Anthropometric measures as body weight, BMI, waist and waist-to-hip ratio (WHR) were assessed by classical methods. Fat mass (FM) was measured by bio impedance. The prevalence of the G1422A variant was not significantly different between cases and controls (OR = 1.056; P = 0.626). In obese women, no meaningful associations between CNR1 genotype and anthropometric parameters were found. In obese men, CNR1 1422 A/A genotype was significantly associated with higher WHR (P = 0.009) and waist circumference (P = 0.008) after adjusting for age and BMI. Fat mass percentage showed an association (P = 0.011) which disappeared after adjusting for age and BMI. A trend for an association was seen for fat mass (unadjusted P = 0.099; adjusted P = 0.033). Our data indicate that the G1422A polymorphism in the CNR1 gene is associated with increased abdominal adiposity in obese men. PMID- 17873326 TI - Two novel genotypes of the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in patients with Gitelman's syndrome. AB - Gitelman's syndrome is an autosomal recessive disorder marked by salt wasting and hypokalaemia resulting from loss-of-function mutations in the SLC12A3 gene that codes for the thiazide-sensitive Na-Cl cotransporter. Gitelman's syndrome is usually distinguished from Bartter's syndrome by the presence of both hypomagnesaemia and hypocalciuria. Although recent advances in molecular genetics may make it possible to both diagnose and differentiate these diseases, the phenotypes sometimes overlap. Here we report two sporadic cases of Gitelman's syndrome and two novel genotypes of SLC12A3. Patient 1 was a compound heterozygote with a known missense mutation, L849H, and a novel mutation, R852H in exon 22. Patient 2 was homozygous for the missense mutation L849H. To our knowledge, this is the first report of a patient homozygous for 849H. Interestingly, both patients were affected with autoimmune thyroid disease. Patient 1 was affected with Hashimoto's disease, and Patient 2 was affected with Graves' disease. The symptoms of Patient 2 were more serious than those of Patient 1. Although the patients both carried the 849H allele (Patient 1 as a heterozygote and Patient 2 as a homozygous), their clinical symptoms differed. The difference in the clinical features may have been due both to phenotypic differences and the fact that Gitelman's syndrome is a complicated disorder. PMID- 17873325 TI - Fat storage is partially dependent on vagal activity and insulin secretion of hypothalamic obese rat. AB - Hypothalamic MSG-obese rats show hyperinsulinemia and tissue insulin resistance, and they display intense parasympathetic activity. Current analysis investigates whether early subdiaphragmatic vagotomy prevents tissue insulin sensitivity impairment in adult obese MSG-rats. Hypothalamic obesity was induced by MSG (4 mg/g BW), daily, from birth up to 5 days. Control animals receiving saline solution. On the 30th day rats underwent bilateral subdiaphragmatic vagotomy or sham surgery. An intravenous glucose tolerance test (i.v.GTT) was performed when rats turned 90 days old. Total white fat tissue (WAT) from rat carcass was extracted and isolated; the interscapular brown fat tissue (IBAT) was weighed. Rather than blocking obesity, vagotomy reduced WAT and IBAT in MSG-obese rats when the latter were compared to sham MSG-rats. High blood fasting insulin and normal glucose levels were also observed in MSG-obese rats. Although glucose intolerance, high insulin secretion, and significant insulin resistance were recorded, vagotomy improved fasting insulinemia, glucose tolerance and insulin tissue sensitivity in MSG-obese rats. Results suggest that increased fat accumulation is caused, at least in part, by high blood insulin concentration, and enhanced parasympathetic activity on MSG-obese rats. PMID- 17873327 TI - Modulation of cardiac oxytocin receptor and estrogen receptor alpha mRNAs expression following neonatal oxytocin treatment. AB - Oxytocin (OT) is known for its role in reproduction. However, evidence has emerged suggesting its involvement in the regulation of the cardiovascular system. Here we examine the hypothesis that neonatal exposure to OT can have both short-term and long-lasting consequences on gene expression in heart tissue. On the first day of postnatal life, female and male prairie voles (Microtus ochrogaster) were randomly assigned to receive one of following treatments: 50 microl i.p. injection of (a) 3 microg OT (b) 0.3 microg of OT antagonist (OTA), or (c) isotonic saline (SAL). Hearts were collected on postnatal day 1 (D1, 2 h after injection), day 8 (D8), or day 21 (D21), and the mRNA expression for OT receptor (OTR), estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta as a function of age, treatment, and sex were measured using RT-PCR. Neonatal treatment with OT showed a marked increase in cardiac OTR mRNA expression on postnatal D1, but not D8 or D21, in both female and male animals. ERalpha increased as a function of OT treatment only in females. Although significant treatment effects were no longer detected in D8 or D21 animals, there were significant changes in the relative expression of all types of mRNA between D1 and D21 with age-related declines in OTR and ERbeta and increases in ERalpha Neonatal treatment with OTA showed no changes in cardiac OTR, ERalpha, or ERbeta mRNAs expression. The results indicate that during the early postnatal period OT can have rapid effects on the expression of OTR and ERalpha mRNAs and that these effects are mitigated by D8 or D21. Also, with the exception of ERalpha mRNA, the effects are the same in both sexes. PMID- 17873328 TI - Sex-specific effects of androgen and estrogen on proliferation of the embryonic chicken hypothalamic neurons. AB - Effects of androgen and estrogen on proliferation of hypothalamic neurons were evaluated by a chicken hypothalamic neuron-glia coculture model. Hypothalamic cells were dispersed from 17-day-old embryos and challenged with testosterone (T) and 17beta-estradiol (E2) alone or combined with androgen receptor antagonist flutamide, estrogen receptor antagonist tamoxifen, or aromatase inhibitor letrozole for 48 h. The neuron number was counted and the proliferating cells were identified by immunocytochemistry of proliferating cell nuclear antigen (PCNA) and 5-bromo-2-deoxyuridine (BrdU) incorporation. Results showed that both E2 and T stimulated proliferation of hypothalamic neurons. E2 showed more intensive effect on females and this promoting effect was abrogated by tamoxifen. T played more intensive effect on males and the effect was inhibited by flutamide, tamoxifen, or letrozole. The above results indicated that E2 stimulated neuron proliferation through estrogenic actions with more sensitive effect on females and T promoted neuron proliferation through both androgenic and estrogenic actions with more intense effect on males. These observations suggested that steroid hormones influence the proliferation of hypothalamic neurons in a sexually dimorphic manner during the development of chicken embryos. PMID- 17873329 TI - Tyrosine receptor kinase B (TrkB) protein expression in the human endometrium. AB - Tyrosine kinase receptor B (TrkB) gene expression, a neurotrophic factor receptor expressed in the brain and ovary, has recently been identified in deep infiltrating endometriosis by gene array. TrkB is thought to be important in resistance to anchorage independent apoptosis (ANOIKIS) and thus could be important in the pathogenesis of endometriosis. However, TrkB protein expression in the eutopic endometrium of women with and without endometriosis is unknown. Therefore, we examined TrKB protein expression in the endometrium by Western blot (n = 50) and immunohistochemistry (n = 17). Immunoblots of endometrial biopsies were prepared from women with endometriosis (n = 21) vs. healthy controls (n = 29) undergoing benign gynecological surgery at McMaster University Medical Centre. TrkB protein expression was significantly higher in immunoblots from women with endometriosis compared to women without endometriosis. In samples of archived paraffin-embedded endometrial tissue TrkB was localized to the cytoplasm of epithelial cells of the eutopic endometrium from women with endometriosis (n = 7) and without endometriosis (n = 10). We conclude that TrkB protein is expressed in human endometrium. Our results also suggest that TrkB expression may be greater in women with endometriosis compared to women without endometriosis. PMID- 17873330 TI - Hypothyroidism and hyperthyroidism modulates Ras-MAPK intracellular pathway in rat thyroids. AB - Thyrotrophin induces proliferation and function in thyroid cells acting through a seven transmembrane G protein-coupled receptor. The proliferative pathways induced by thyrotropin (TSH) in thyrocytes in vivo are not completely understood yet. The aim of this work is to evaluate if Ras can be induced by TSH in rat thyroids, and whether extracellular regulated kinase (ERK) may be involved in the subsequent intracellular signalling cascade. We induced hypothyroidism in Wistar rats by methimazole (MMI) treatment (0.03% in the drinking water for 21 days). A subset of the hypothyroid rats received T4 (1 microg/100 g bw) during the last 10 days of MMI treatment. Hyperthyroidism was induced by subcutaneous injections of T4 (10 microg/100 g bw) during 10 days in another group of rats. Our data show that in the hypothyroid rats there is a clear positive Ras modulation, but a decrease in pERK. In contrast, thyroidal pERK increases in T4-induced hyperthyroidism, but without any change in RAS, although these changes did not reach statistical significance. Thus, while the rat thyroid proliferation induced by TSH may involve an increase in RAS signalling, the subsequent cascade does not involve ERK phosphorilation, which in fact, increases during T4-induced hyperthyroidism. PMID- 17873331 TI - Obligatory roles for follicle-stimulating hormone (FSH), estradiol and androgens in the induction of small polyfollicular ovarian cysts in hypophysectomized immature rats. AB - Immature hypophysectomized (HYPOXD) rats develop large, polyfollicular ovarian cysts in response to unabated, combined stimulation by subovulatory doses of human chorionic gonadotropin (hCG) and highly purified ovine follicle-stimulating hormone (FSH). Further, circulating amounts of androstenedione (A4) and estradiol (E2), but not testosterone or dihydrotestosterone (DHT), change in parallel with the development of these cysts. To determine the potential roles of either A4 or E2 at the level of the ovary in the induction of ovarian cysts, pellets containing either (1) cholesterol (placebo; controls); (2) A4; or (3) E2 were administered subcutaneously (sc) to immature HYPOXD rats. Some of these animals also received either twice-daily sc injections of 1 IU hCG, or daily s.c. injections of 2 microg FSH, for 13 days. Ovaries and sera were harvested from all treatment groups on the morning of day 14 of the combined-hormone treatment schedule. As expected, ovaries from HYPOXD rats treated with placebo, A4, or E2 pellets (with or without hCG) failed to display antral follicles. Ovaries from HYPOXD rats treated with FSH and a placebo pellet displayed polyfollicular, atretic, small antral follicles with unstimulated thecal shells. In addition, the ovarian stromal-interstitial tissue had an unstimulated appearance. In contrast, ovaries from HYPOXD rats treated with FSH plus either A4 or E2 implants displayed stimulated stromal-interstitial tissue as well as small follicular cysts and precysts with stimulated thecal shells. The number of cysts and precysts observed in the largest ovarian cross-sections for animals treated with FSH + A4 (17.0 +/- 3.0) was less than that observed in the largest ovarian cross-sections for HYPOXD rats treated with FSH + E2 (40.2 +/- 10.1; p < 0.05). To determine if the development of ovarian cysts in response to FSH + A4 was due, at least in part, to the metabolism of A4 to E2, HYPOXD rats were treated with either (1) placebo pellets; (2) pellets containing dihydrotestosterone (DHT) which cannot be metabolized to estrogen; (3) E2 pellets plus DHT pellets (E2 + DHT); (4) FSH + DHT; or (5) FSH + E2 + DHT. The largest ovarian cross-sections from FSH + DHT treated HYPOXD rats displayed 18.3 +/- 4.1 small follicles with a mean diameter of approximately 0.437 mm which possessed few granulosa cells. The thecal and stromal-interstitial tissues in these ovaries were unstimulated, which indicates that these small degenerating follicles were atretic rather than cystic. In contrast, the largest ovarian cross-sections from FSH + E2 + DHT-treated HYPOXD rats displayed 51.6 +/- 2.4 cysts with stimulated thecal shells and a mean diameter of approximately 0.634 mm. Further, these cysts were arranged in a "string of pearls" pattern and the ovarian stromal-interstitial tissue possessed a stimulated appearance. These data demonstrate a direct, unambiguous role at the level of the ovary for unabated tonic stimulation by FSH plus estrogen in the development of small polyfollicular cysts in HYPOXD rats. Further, the data also indicate that, at least in HYPOXD rats, combined, tonic stimulation by FSH plus estrogen and androgen is sufficient for the development of small, polyfollicular ovarian cysts in a "string of pearls" pattern. These observations are in distinct contrast to our previous observations that tonic stimulation by FSH + hCG results in the induction of large ovarian cysts in HYPOXD rats and provide tantalizing new insights regarding the potential importance of specific hormones at the level of the ovary in the induction of specific types of cystic follicles. PMID- 17873332 TI - Expression and regulation of type II integral membrane protein family members in mouse male reproductive tissues. AB - Type II Integral membrane protein (Itm2) family consists of three members, Itm2a, Itm2b and Itm2c. ITM2B has been shown to be closely related to human male reproduction. The expression and regulation of Itm2 family members in male reproductive tissues are still unknown. The aim of the present study was to examine the expression pattern and regulation of Itm2 family members in male mouse reproductive tissues during sexual maturation, castration, and busulfan treatment by in situ hybridization. During sexual maturation, a low level of Itm2a was detected in testicular interstitium on days 30-70. Itm2b expression was basally detected in the epithelium of seminiferous tubules on days 1, 5, and 10, and then the signal was transited into Leydig cells and gradually increased up to day 70. Itm2c was detected at a basal to low level in the testis during sexual maturation. Both Itm2a and Itm2c were not detected in the epididymis and vas deferens during sexual maturation. In contrast, Itm2b expression was detected in the epithelium of caput, corpus, cauda epididymis, and vas deferens from neonate to adult mice. In the caput, Itm2b expression reached the highest level on day 15 and maintained this level up to day 70. However, in corpus and cauda epididymis, the signals gradually reached a high level from days 15 to 70. In vas deferens, Itm2b gradually increased to a high level from days 25 to 70. In the castrated mice, Itm2b expression was upregulated in epididymis and vas deferens by testosterone treatments. When busulfan was used to specifically destroy the germ cells in the testis, there were no observable effects on Itm2b expression in the male reproductive organs. Our results suggested that Itm2b mRNA was differentially expressed in mouse male reproductive tissues, during sexual maturation and up-regulated by testosterone. PMID- 17873334 TI - Genetic diagnosis of multiple affected tissues in a patient with McCune-Albright syndrome. AB - McCune-Albright syndrome (MAS) is a sporadic disorder characterized by the classic triad of polyostotic fibrous dysplasia, cafe-au-lait' skin pigmentation, and hyperfunctional endocrinopathy. It is caused by embryonic somatic mutations leading to the substitution of His or Cys for Arg at amino acid 201 of the alpha subunit of the signal transduction protein Gs (Gsalpha). A 32-year-old man was diagnosed as McCune-Albright syndrome with the following findings: polyostotic fibrous dysplasia, cafe-au-lait' spots and acromegaly. An ultrasonic examination showed that he had left-pleural effusion, which disappeared after almost a year without special treatment. Genomic DNA was isolated from the peripheral blood, bone tissue, skin lesion and pleura samples of the patient. Then PCR and direct sequencing were performed. An activating mutation of the Gsalpha gene (Arg201Cys) was found in the genomic DNA isolated from the peripheral blood and the bone tissue, but not in genomic DNA isolated from the skin and pleura samples. PMID- 17873335 TI - Recent advances in fluorescence cross-correlation spectroscopy. AB - Fluorescence cross-correlation spectroscopy (FCCS) is a method that measures the temporal fluorescence fluctuations coming from two differently labeled molecules diffusing through a small sample volume. Cross-correlation analysis of the fluorescence signals from separate detection channels extracts information of the dynamics of the dual-labeled molecules. FCCS has become an essential tool for the characterization of diffusion coefficients, binding constants, kinetic rates of binding, and determining molecular interactions in solutions and cells. By cross correlating between two focal spots, flow properties could also be measured. Recent developments in FCCS have been targeted at using different experimental schemes to improve on the sensitivity and address their limitations such as cross talk and alignment issues. This review presents an overview of the different excitation and detection methodologies used in FCCS and their biological applications. This is followed by a description of the fluorescent probes currently available for the different methods. This will introduce biological readers to FCCS and its related techniques and provide a starting point to selecting which experimental scheme is suitable for their type of biological study. PMID- 17873333 TI - Metabolic and reproductive consequences of the serotonin transporter promoter polymorphism (5-HTTLPR) in adult female rhesus monkeys (Macaca mulatta). AB - The serotonin (5HT) reuptake transporter (SERT) plays a key role in 5HT homeostasis by recycling 5HT into the presynaptic neurons. Recently, polymorphisms in the length of the promoter region of the gene that encodes SERT have been linked to functional differences in reactivity to psychosocial stress, as the short (s) promoter length allele shows reduced transcriptionally activity in vitro and is associated with reduced 5HT activity and increased vulnerability to affective disorders. Given 5HT's important role in appetite regulation, polymorphisms in the SERT gene could also affect metabolic parameters. In addition, since reduced 5HT activity may also predispose females to reproductive deficits, polymorphisms in the SERT gene may help explain individual differences in ovulatory function. The present study, using a rhesus monkey model, tested the hypothesis that the presence of the s-variant allele would be associated with altered metabolic regulation and impaired ovulatory cycles compared with the l/l genotype. Females homozygous for the long allele in the SERT gene (l/l, n = 19) were compared to those with the s-variant allele (l/s or s/s, n = 20). All females had similar social histories. Body weights (P = 0.026) but not heights (P = 0.618) were significantly lower in s-variant compared to l/l females. In addition, both BMI (P = 0.032) and sagittal abdominal diameters (SAD) (P = 0.031), as indices of adiposity, were significantly lower in s-variant females. Consistent with these differences, fasting and non-fasting levels of leptin were significantly lower in s-variant females (P = 0.002). While there were no genotype differences in non-fasting levels of insulin, s-variant females had significantly lower concentrations of insulin during a fast than did l/l females (P = 0.052). Neither glucose, T 3, T 4, nor ghrelin varied significantly between groups during either the fasted or non-fasted condition (P > 0.05). Analysis of a subset of females indicated that significantly fewer s-variant females (62.5%) exhibited ovulatory cycles than l/l females (100%, P < 0.05). However, there were no differences in serum estradiol or progesterone in l/l females and those s variant females that did ovulate (P > 0.05). In addition, females with the s variant genotype also had reduced 5HT activity (P = 0.030), assessed from the acute increase in serum prolactin following the administration of the 5HT reuptake inhibitor, citalopram. Finally, s-variant females were significantly less responsive to glucocorticoid negative feedback (P = 0.030) yet more responsive to corticotropin releasing hormone (CRH, P = 0.016) in terms of plasma cortisol than were l/l females. These data indicate that adult female rhesus monkeys with the s-variant polymorphism in the SERT gene exhibit metabolic and reproductive alterations in conjunction with reduced serotonergic responsivity and increased LHPA activity and suggest the possibility that this genotype may predispose females exposed to psychosocial stressors to further metabolic and reproductive deficits. PMID- 17873336 TI - Mathematical models of cell motility. AB - Cell motility is an essential biological action in the creation, operation and maintenance of our bodies. Developing mathematical models elucidating cell motility will greatly advance our understanding of this fundamental biological process. With accurate models it is possible to explore many permutations of the same event and concisely investigate their outcome. While great advancements have been made in experimental studies of cell motility, it now has somewhat fallen on mathematical models to taking a leading role in future developments. The obvious reason for this is the complexity of cell motility. Employing the processing power of today's computers will give researches the ability to run complex biophysical and biochemical scenarios, without the inherent difficulty and time associated with in vitro investigations. Before any great advancement can be made, the basics of cell motility will have to be well-defined. Without this, complicated mathematical models will be hindered by their inherent conjecture. This review will look at current mathematical investigations of cell motility, explore the reasoning behind such work and conclude with how best to advance this interesting and challenging research area. PMID- 17873337 TI - An overview of DNA and RNA bindings to antioxidant flavonoids. AB - In this report we are examining how the antioxidant flavonoids can prevent DNA damage and what mechanism of action is involved in the process. Flavonoids are strong antioxidants that prevent DNA damage. The anticancer and antiviral activities of these natural products are implicated in their mechanism of actions. We study the interactions of quercetin (que), kaempferol (kae), and delphinidin (del) with DNA and transfer RNA in aqueous solution at physiological conditions, using constant DNA or RNA concentration 6.25 mmol (phosphate) and various pigment/polynucleotide(phosphate) ratios of 1/65 to 1 (DNA) and 1/48 to 1/8 (tRNA). The structural analysis showed quercetin, kaempferol, and delphinidin intercalate DNA and RNA duplexes with minor external binding to the major or minor groove and the backbone phosphate group with overall binding constants for DNA adducts K(que) = 7.25 (+/-0.65) x 10(4) M(-1), K(kae) = 3.60 (+/-0.33) x 10(4) M(-1), and K(del) = 1.66 (+/-0.25) x 104 (-1) and for tRNA adducts K(que) = 4.80 (+/-0.50) x 10(4) M(-1), K(kae) = 4.65 (+/-0.45) x 10(4) M(-1), and K(del) = 9.47 (+/-0.70) x 10(4) M(-1). The stability of adduct formation is in the order of del>que>kae for tRNA and que>kae>del for DNA. Low flavonoid concentration induces helical stabilization, whereas high pigment content causes helix opening. A partial B to A-DNA transition occurs at high drug concentration, while tRNA remains in A-family structure. The antioxidant activity of flavonoids changes in order delphinidin>quercetin>kaempferol. The results show intercalated flavonoids can make them strong antioxidants to protect DNA from harmful free radical reactions. PMID- 17873338 TI - Recent progress on the analysis of power-law features in complex cellular networks. AB - Complex interactions between different kinds of bio-molecules and essential nutrients are responsible for cellular functions. Rapid advances in theoretical modeling and experimental analyses have shown that drastically different biological and non-biological networks share a common architecture. That is, the probability that a selected node in the network has exactly k edges decays as a power-law. This finding has definitely opened an intense research and debate on the origin and implications of this ubiquitous pattern. In this review, we describe the recent progress on the emergence of power-law distributions in cellular networks. We first show the internal characteristics of the observed complex networks uncovered using graph theory. We then briefly review some works that have significantly contributed to the theoretical analysis of cellular networks and systems, from metabolic and protein networks to gene expression profiles. This prevalent topology observed in so many diverse biological systems suggests the existence of generic laws and organizing principles behind the cellular networks. PMID- 17873339 TI - Role of advanced glycation end products in hypertension and atherosclerosis: therapeutic implications. AB - The vascular diseases, hypertension and atherosclerosis, affect millions of individuals worldwide, and account for a large number of deaths globally. A better understanding of the mechanism of these conditions will lead to more specific and effective therapies. Hypertension and atherosclerosis are both characterized by insulin resistance, and we suggest that this plays a major role in their etiology. The cause of insulin resistance is not known, but may be a result of a combination of genetic and lifestyle factors. In insulin resistance, alterations in glucose and lipid metabolism lead to the production of excess aldehydes including glyoxal and methylglyoxal. These aldehydes react non enzymatically with free amino and sulfhydryl groups of amino acids of proteins to form stable conjugates called advanced glycation end products (AGEs). AGEs act directly, as well as via receptors to alter the function of many intra- and extracellular proteins including antioxidant and metabolic enzymes, calcium channels, lipoproteins, and transcriptional and structural proteins. This results in endothelial dysfunction, inflammation and oxidative stress. All these changes are characteristic of hypertension and atherosclerosis. Human and animal studies have demonstrated that increased AGEs are also associated with these conditions. A pathological role for AGEs is substantiated by studies showing that therapies that attenuate insulin resistance and/or lower AGEs, are effective in decreasing oxidative stress, lowering blood pressure, and attenuating atherosclerotic vascular changes. These interventions include lipoic acid and other antioxidants, AGE breakers or soluble receptors of AGEs, and aldehyde-binding agents like cysteine. Such therapies may offer alternative specific means to treat hypertension and atherosclerosis. An adjunct therapy may be to implement lifestyle changes such as weight reduction, regular exercise, smoking cessation, and increasing dietary intake of fruits and vegetables that also decrease insulin resistance as well as oxidative stress. PMID- 17873341 TI - Breast cancer stem cells: a case of mistaken identity? PMID- 17873342 TI - Breast cancer stem cells: the other side of the story. PMID- 17873344 TI - The emerging picture of the mouse mammary stem cell. AB - The isolation and characterisation of mammary stem cells is an important step towards elucidating the hierarchy of epithelial cell development in the mammary gland and identifying cells that are targets of breast carcinogenesis. Mammary stem cells have recently been prospectively isolated through the identification of specific cell surface markers and in vivo transplantation into cleared fat pads. These cells were demonstrated to reconstitute an entire mammary gland comprising all mature epithelial cell types and to be capable of self-renewal on serial transplantation, thus possessing the defining features of stem cells. Notably, mouse mammary stem cells were found to share the hallmark properties of the basal subtype of breast cancer. This review will summarize the strategy used in the identification of mouse mammary stem cells and their characterisation. PMID- 17873345 TI - Prospective isolation and functional analysis of stem and differentiated cells from the mouse mammary gland. AB - Prospective isolation and in vitro and in vivo analysis of primary mouse mammary epithelial cells has been used to separate cell subpopulations and identify stem, progenitor and differentiated cell compartments. Progress has been made from cell separation strategies based on a single marker of the luminal epithelial or myoepithelial compartments to use of markers that allow simultaneous isolation of non-epithelial, basal/myoepithelial and luminal epithelial cells. Transplant analysis has shown that mammary stem cells are found in the basal/myoepithelial compartment, whereas in vitro colony progenitors are found in the luminal compartment. A basal population enriched for stem cell activity can be purified from the myoepithelial cells and the most recent data shows that the luminal population can now be prospectively split into estrogen receptor positive and estrogen receptor negative cells. Future work aims to molecularly characterise these populations to identify new drug targets, which can be used to specifically kill breast cancer stem cells. PMID- 17873346 TI - Of microenvironments and mammary stem cells. AB - In most adult tissues there reside pools of stem and progenitor cells inside specialized microenvironments referred to as niches. The niche protects the stem cells from inappropriate expansion and directs their critical functions. Thus guided, stem cells are able to maintain tissue homeostasis throughout the ebb and flow of metabolic and physical demands encountered over a lifetime. Indeed, a pool of stem cells maintains mammary gland structure throughout development, and responds to the physiological demands associated with pregnancy. This review discusses how stem cells were identified in both human and mouse mammary glands; each requiring different techniques that were determined by differing biological needs and ethical constraints. These studies together create a robust portrait of mammary gland biology and identify the location of the stem cell niche, elucidate a developmental hierarchy, and suggest how the niche might be manipulated for therapeutic benefit. PMID- 17873347 TI - Stem cells and the stem cell niche in the breast: an integrated hormonal and developmental perspective. AB - The mammary gland is a unique organ in that it undergoes most of its development after birth under the control of systemic hormones. Whereas in most other organs stem cells divide in response to local stimuli, to replace lost cells, in the mammary gland large numbers of cells need to be generated at specific times during puberty, estrous cycles and pregnancy to generate new tissue structures. This puts special demands on the mammary stem cells and requires coordination of local events with systemic needs. Our aim is to understand how the female reproductive hormones control mammary gland development and influence tumorigenesis. We have shown that steroid hormones act in a paracrine fashion in the mammary gland delegating different functions to locally produced factors. These in turn, affect cell-cell interactions that result in changes of cell behavior required for morphogenesis and differentiation. Here, we discuss how these hormonally regulated paracrine interactions may impinge on stem cells and the stem cell niche and how this integration of signals adds extra levels of complexity to current mammary stem cell models. We propose a model whereby the stem cell niches change depending on the developmental stages and the hormonal milieu. According to this model, repeated hormone stimulation of stem cells and their niches in the course of menstrual cycles may be an important early event in breast carcinogenesis and may explain the conundrum why breast cancer risk increases with the number of menstrual cycles experienced prior to a first pregnancy. PMID- 17873348 TI - Wnt signaling, stem cells, and the cellular origin of breast cancer. AB - The breast epithelium comprises cells at different stages of differentiation, including stem cells, progenitor cells, and more differentiated epithelial and myoepithelial cells. Wnt signaling plays a critical role in regulating stem/progenitor cells in the mammary gland as well as other tissue compartments. Furthermore, there is strong evidence suggesting that aberrant activation of Wnt signaling induces mammary tumors from stem/progenitor cells, and that Wnt exerts its oncogenic effects through LRP5/6-mediated activation of beta-catenin and mTOR pathways. Recent studies using avian retrovirus-mediated introduction of oncogenes into a small subset of somatic mammary cells suggest that polyoma middle T antigen (PyMT) may also preferentially transform stem/progenitor cells. These observations suggest that stem/progenitor cells in the mammary gland may be especially susceptible to oncogenic transformation. Whether more differentiated cells may also be transformed by particular oncogenes is actively debated; it is presently unclear whether stem cells or differentiated mammary cells are more susceptible to transformation by individual oncogenes. Better stem cell and progenitor cell markers as well as the ability to specifically target oncogenes into different mammary cell types will be needed to determine the spectrum of oncogene transformation for stem cells versus more differentiated cells. PMID- 17873350 TI - Breast cancer stem cells-research opportunities utilizing mathematical modeling. AB - There is increasing evidence for the "cancer stem cell hypothesis" which holds that cancers originate in tissue stem cells or progenitor cells. As a result of this, cancers are driven by a cellular subcomponent that retains stem cell properties. Among these properties are self-renewal and multi-lineage differentiation. The biological processes which account for stem cell properties are currently being elucidated. Cancer stem cells maintain many of the same characteristics of their normal counterparts. The combination of biological research with mathematical modeling may provide for a greater understanding of the complex picture of breast cancer stem cells and assist cancer biologists and clinical oncologists in designing and testing novel therapeutic strategies. PMID- 17873349 TI - Mammary stem cells and breast cancer--role of Notch signalling. AB - Adult stem cells are found in numerous tissues of the body and play a role in tissue development, replacement and repair. Evidence shows that breast stem cells are multipotent and can self renew, which are key characteristics of stem cells, and a single cell enriched with cell surface markers has the ability to grow a fully functional mammary gland in vivo. Many groups have extrapolated the cancer stem cell hypothesis from the haematopoietic system to solid cancers, where using in vitro culture techniques and in vivo transplant models have established evidence of cancer stem cells in colon, pancreas, prostate, brain and breast cancers. In the report we describe the evidence for breast cancer stem cells; studies consistently show that stem cell like and breast cancer initiating populations can be enriched using cell surface makers CD44+/CD24- and have upregulated genes which include Notch. Notch signalling has been highlighted as a pathway involved in the development of the breast and is frequently dysregulated in invasive breast cancer. We have investigated the role of Notch in a pre invasive breast lesion, ductal carcinoma in situ (DCIS), and have found that aberrant activation of Notch signalling is an early event in breast cancer. High expression of Notch 1 intracellular domain (NICD) in DCIS also predicted a reduced time to recurrence 5 years after surgery. Using a non-adherent sphere culture technique we have grown DCIS mammospheres from primary DCIS tissue, where self-renewal capacity, measured by the number of mammosphere initiating cells, were increased from normal breast tissue. A gamma-secretase inhibitor, DAPT, which inhibits all four Notch receptors and a Notch 4 neutralising antibody were shown to reduce DCIS mammosphere formation, indicating that Notch signalling and other stem cell self-renewal pathways may represent novel therapeutic targets to prevent recurrence of pre-invasive and invasive breast cancer. PMID- 17873351 TI - Calorimetric study of nonspecific interaction between lead ions and bovine serum albumin. AB - The nonspecific interaction between lead ions and bovine serum albumin (BSA) was studied by the calorimetric technique. According to thermodynamic parameters calculated from titration curves, it can be seen that the increase of intermolecular bond energies and decrease of disorder in the system were accompanied by a binding process. This kind of binding is the reaction "driven by enthalpy." Furthermore, the denatured BSA has more binding sites and more changes in enthalpy and entropy than the native BSA because the unfolded chain of denatured BSA could adapt itself to the binding reaction with lead ions more easily. PMID- 17873352 TI - Comparative bioavailability of mineral-enriched gluconates and yeast in rat liver after depletion-repletion feeding. AB - There are many forms of mineral supplements currently available. Among these mineral-enriched gluconates and yeast are considered two of the more biologically available supplements. The purpose of this study was to use zinc (Zn)- or copper (Cu)-deficient rats to determine whether the organically bound mineral in yeast or the salt gluconate form was more bioavailable, i.e., is absorbed and found in a greater concentration in liver. It was demonstrated that Zn-enriched yeast was 3.7 times more bioavailable than the Zn gluconate and that Cu-enriched yeast was 1.4 times more bioavailable than the Cu gluconate. PMID- 17873353 TI - Zinc deficiency increases platelet oxidative stress in nephrectomized rats. AB - We previously reported that reduced platelet endogenous antioxidant enzymes activities are related to the low plasma zinc level in patients with end-stage renal failure (ESRF). In this study, we attempt to evaluate whether dietary zinc deprivation reduces the activities of endogenous antioxidant and then enhances oxidative stress in the unstimulated platelet of normal and 5/6 nephrectomized (Nx) rats because increased platelet oxidative stress is suggested to involve in the incidence of thrombotic and atherosclerotic diseases. Male Sprague-Dawley rats (n = 48) were fed a zinc-deficient diet and deionized distilled water for 1 week to induce reduction of plasma zinc level. Half of the rats continued on this diet for 4 weeks as zinc-deplete group, and the other half were maintained on the same diet but with zinc-supplemented water (120 mg/L zinc sulfate solution) to correct the reduction of plasma zinc level as zinc-replete group. Half of each group underwent 5/6 Nx, while the other half underwent sham operation. Another 12 normal rats were fed standard rat chow (containing 23.4% protein and 50 ppm zinc) and drank deionized distilled water as normal control rats. In zinc-deplete rats including sham-operated and 5/6 Nx rats exhibited lower endogenous antioxidant enzymes activities such as reduced glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GPX) and higher malondialdehyde (MDA) levels than normal control rats in the unstimulated platelets. However, in zinc-replete rats including sham-operated and 5/6 Nx rats have a normal endogenous antioxidant enzymes activity and normal MDA levels in the unstimulated platelets. We suggest that in uremia, the low plasma zinc level may be a risk factor for thrombotic and atherosclerotic diseases because it reduces the activities of endogenous antioxidant enzymes and increases oxidative stress in the unstimulated platelet. PMID- 17873354 TI - Effects of nano-anatase TiO2 on absorption, distribution of light, and photoreduction activities of chloroplast membrane of spinach. AB - The effects of nano-anatase TiO2 on light absorption, distribution, and conversion, and photoreduction activities of spinach chloroplast were studied by spectroscopy. Several effects of nano-anatase TiO2 were observed: (1) the absorption peak intensity of the chloroplast was obviously increased in red and blue region, the ratio of the Soret band and Q band was higher than that of the control; (2) the great enhancement of fluorescence quantum yield near 680 nm of the chloroplast was observed, the quantum yield under excitation wavelength of 480 nm was higher than the excitation wavelength of 440 nm; (3) the excitation peak intensity near 440 and 480 nm of the chloroplast significantly rose under emission wavelength of 680 nm, and F 480 / F 440 ratio was reduced; (4) when emission wavelength was at 720 nm, the excitation peaks near 650 and 680 nm were obviously raised, and F 650 / F 680 ratio rose; (5) the rate of whole chain electron transport, photochemical activities of PSII DCPIP photoreduction and oxygen evolution were greatly improved, but the photoreduction activities of PSI were a little changed. Together, the studies of the experiments showed that nano anatase TiO2 could increase absorption of light on spinach chloroplast and promote excitation energy to be absorbed by LHCII and transferred to PSII and improve excitation energy from PSI to be transferred to PSII, thus, promote the conversion from light energy to electron energy and accelerate electron transport, water photolysis, and oxygen evolution. PMID- 17873355 TI - Effects of selenium and vitamin E, in addition to melatonin, against oxidative stress caused by cadmium in rats. AB - The present study was carried to evaluate the protective effects of melatonin alone and vitamin E with selenium combination against high dose cadmium-induced oxidative stress in rats. The control group received subcutaneous physiological saline. The first study group administered cadmium chloride (CdCl2) by subcutaneous injection of dose of 1 mg/kg. The second study group administered cadmium plus vitamin E with selenium (1 mg/kg sodium selenite with 60 mg/kg vitamin E); the third study group administered cadmium plus 10 mg/kg melatonin (MLT); the fourth study group administered CdCl2 plus a combination of melatonin in addition to vitamin E and selenium for a month. Determination levels of plasma malondialdehyde (MDA), glutathione peroxidase (GSH-Px), blood superoxide dismutase (SOD), creatinine alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and urea were measured in serum. In only CdCl2 administered group, the MDA, creatinine, ALT, AST, ALP, and urea levels in the serum were significantly higher than the control group (p < 0.05). Whereas in all other groups, this values were significantly lower than the only CdCl2 administered group (p < 0.05). Erythrocytes GSH-Px, serum SOD activities of only CdCl2 received group were significantly lower than the control group (p < 0.05). In conclusion, vitamin E + Se, melatonin and vitamin E, and Se, in addition to MLT combinations, had protective effects against high dose cadmium-induced oxidative damage. PMID- 17873356 TI - Selected zinc metabolism parameters and left ventricle mass in echocardiographic examination in primary arterial hypertension. AB - The basal systolic and diastolic blood pressure, body mass index, left ventricular mass, serum and lymphocyte zinc levels, serum aldosterone, plasma rennin and angiotensin-converting enzyme activities, sodium and potassium levels, and the total and ouabain-dependent rate constants of zinc efflux from lymphocytes were measured in a group of 41 individuals of both sexes (overall age 46.3 +/- 11.4 years), of which 18 were women (48.5 +/- 7.1 years old) and 23 were men (44.7 +/- 13.8 years old). There were no significant differences between these parameters while dividing the subjects into groups according to sex, despite differences in weight, left ventricle mass, plasma rennin activity, and serum aldosterone content. Only the total and ouabain-dependent rate constants of zinc efflux from lymphocytes slightly negatively correlated to left ventricular mass, r = -0.30 to r = -0.36. This may constitute indirect evidence of zinc deficiency in cardiomyocytes of some hypertensive individuals with left ventricular hypertrophy. PMID- 17873357 TI - Separation and determination of heavy metals associated with low molecular weight chelators in xylem saps of Indian mustard (Brassica juncea) by size exclusion chromatography and atomic absorption spectrometry. AB - To elucidate the role of low molecular weight chelators in long-distance root-to shoot transport of heavy metals in Indian mustard, an "off-line" size exclusion high-performance liquid chromatography-graphite furnace atomic absorption spectrometry was developed to investigate heavy metals associated with low molecular weight chelators in xylem saps of Indian mustard (Brassica juncea). The size exclusion chromatogram presented only the peaks with molecular weight for all xylem saps and directly indicated the long-distance transport of phytochelatins (PCs) of Indian mustard under Cd stress. In the absence of Cd stress, only organic acids and inorganic anions participated in the long-distance transport of Cd, but organic acids, inorganic anions, glutathione (GSH), and cysteine might relate to the long-distance transport of Cu or Zn. In the presence of Cd stress, PCs were induced, and Cd ions in xylem saps were associated with the induced PCs. As the Cd levels in nutrient solution increased, more Cd in xylem saps adopted the form of PC-Cd. Although PCs might participate in the long distance transport of Cd under Cd stress, the majority of Cd was still transported by organic acids and inorganic anions in xylem vessels. Moreover, results indicated the existence of complexation competition for GSH and cysteine between Cd and Cu (or Zn) and complexation competition for Cd between PCs and GSH (or cysteine) in xylem vessels. Our work might be very useful for understanding the mechanism of long-distance transport of heavy metals in hyperaccumulator. PMID- 17873358 TI - Spectroscopic characterization of a VO2+ complex of oxodiacetic acid and its bioactivity on osteoblast-like cells in culture. AB - The oxovanadium(IV) complex of oxodiacetic acid (H2oda) of stoichiometry [VO(oda)(H2O)2], which presents an unprecedented tridentate OOO coordination, was thoroughly characterized by infrared, Raman, electronic, and electron paramagnetic resonance spectroscopies. The biological activity of the complex on the cell proliferation and differentiation was tested on osteoblast-like cells (MC3T3E1 osteoblastic mouse calvaria-derived cells and UMR106 rat osteosarcoma derived cells) in culture. The complex caused inhibition of cellular proliferation in both osteoblast-like cells in culture, but the cytotoxicity was stronger in the normal (MC3T3E1) than in the tumoral (UMR106) osteoblasts. The effect of the complex in cell differentiation was tested through the specific activity of alkaline phosphatase of the UMR106 cells because they expressed a high activity of this enzyme. What occurs with other vanadium compounds [VO(oda)(H2O)2] is an inhibitory agent of osteoblast differentiation. PMID- 17873359 TI - Plasma zinc concentration, body composition and physical activity in obese preschool children. AB - Zinc (Zn) deficiency and obesity can be observed together in some developing countries. Zn deficiency may enhance fat deposition and decrease lean mass accrual, which in turn, appears to influence physical activity (PA), although this has not yet been evaluated in obese children. The objective of the study was to find out the association between measurements of plasma Zn and serum leptin, body composition, and PA in Chilean obese preschool children. Seventy-two 18- to 36-month-old obese children [weight-for-length/height z score (WHZ) > 2.0 SD], belonging to low socioeconomic communities, participated in the study. Plasma Zn, serum leptin, weight, waist circumference, height, total body water (TBW) assessed by deuterium isotopic dilution technique and daily activity, measured by registering 48 h with an accelerometer, were evaluated. We found 82% of children with WHZ > 3 SD. The geometric mean Zn intake was 6.2 +/- 2.5 mg/day. The mean plasma Zn was 91.8 +/- 11.4 microg/dL, with 10% of the children having levels <80 microg/dL. No correlation was found between plasma Zn concentrations and either weight, WHZ, or waist circumference. Serum leptin was lower in males than in females (2.9 +/- 2.8 vs 6.8 +/- 5.0 ng/mL, respectively; p < 0.001). TBW was different between males and females (56.2 +/- 5.4 vs 52.8 +/- 4.3% body weight, respectively; p = 0.004), but no significant association was found between TBW and plasma Zn. Moderate + intense PA, (as percentage of wake time), was greater in males than in females (6.3 +/- 3.1% vs 3.4 +/- 2.3%, respectively; p < 0.001), but it was not significantly correlated to plasma Zn. In conclusion, plasma Zn was not associated with body composition as assessed by TBW, serum leptin, or with the magnitude of physical activity in Chilean overweight preschool children. PMID- 17873360 TI - Oral administration of lycopene reverses cadmium-suppressed body weight loss and lipid peroxidation in rats. AB - Cadmium (Cd) exposure has been recognized to result in a wide variety of cellular responses, including oxidative stress and body weight loss. The aim of the present study was to examine the effect of lycopene supplementation on the antioxidant defense system, lipid peroxidation (LPO) level, nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha) production, and body weight in Cd-exposed rats. Animals were divided into four groups (n = 7): control, Cd-treated, Cd plus lycopene-treated, and lycopene-treated. Cadmium (as CdCl2) was administrated orally for 20 days (6.6 mg kg(-1) day(-1)), and lycopene (10 mg kg(-1) day(-1)) was similarly administered. Lycopene administration significantly suppressed Cd induced LPO in plasma and kidney homogenates. Lycopene also reversed Cd-decreased body weight compared to the control. Cadmium treatment had diverse effects on the antioxidant enzyme activities. Although antioxidant superoxide dismutase activity was unchanged, glutathione peroxidase activity was decreased, and catalase activity was elevated in kidney homogenates of Cd-administrated group. However, lycopene treatment reversed Cd-changed enzyme activities to the control level. Xanthine oxidase activity and TNF-alpha concentration were not altered by Cd administration, indicating that superoxide anion production and inflammation were not stimulated. Cadmium did not change NO levels in kidney homogenates but decreased those in plasma, and this effect was not prevented by lycopene supplementation. The result suggests that consumption of adequate levels of lycopene may be useful to prevent heavy-metal-induced LPO and body weight loss. PMID- 17873361 TI - Effect of therapy on serum zinc and copper in primary complex of children. AB - Tuberculosis is a global problem especially in children, more so because of the difficulty in the diagnosis of the disease. There are about 0.5 million deaths every year by this disease, worldwide. There are some reports that, during the disease, there are changes in serum concentrations of zinc and copper, which reach towards normal levels during treatment. Such data for children are scarce, especially in reference to India. Our study indicates that there is an insignificant to significant rise in serum zinc levels in various age groups of children after antitubercular therapy (mean 61.89 +/- 3.21 to 65.24 +/- 3.60 microg/dl) and significant fall in serum copper levels in different age groups of children (mean 129.96 +/- 3.18 to 124.91 +/- 3.48 microg/dl). The Cu/Zn ratio also changed significantly from 2.11 +/- 0.12 to 1.92 +/- 0.12. Because evaluation of available diagnostic criteria for primary complex in children has been found to have high sensitivity, and although this criterion is presently not recommended for diagnosis of primary complex of children, further research can prove its utility in diagnosis and treatment of this disease. PMID- 17873362 TI - Proteomic analysis of human cerebral endothelial cells activated by multiple sclerosis serum and IFNbeta-1b. AB - Several groups have recently described the endothelial cell (EC) as an important target of pathological mediators in multiple sclerosis (MS). Despite the recognition of the EC as a significant target in MS and a possible beneficiary of Beta-interferon therapy, the structural changes which occur in the cerebrovascular endothelium and the effects of interferon-beta 1b on these changes have not been closely evaluated. Disruption or dysregulation of the blood brain barrier (BBB) in MS represents a loss of endothelial integrity, which may facilitate the transendothelial migration of activated leukocytes responsible for the development of demyelinating lesions of MS. We used proteomics (2-dimensional gel electrophoresis and MALDI-MS) to characterize the effects of serum from MS patients with active disease (with and without interferon-beta 1b therapy) on human cerebral endothelial cells. The results of this study revealed the up- and down-regulation of expression of several proteins related to blood vessel development, cell structure, and cell cycle control. Using this approach we have identified protein 14-3-3, metavinculin, myosin-9, plasminogen, reticulocalbin-2 and-3, ribonuclease/angiogenin inhibitor 1, annexin A1, tropomyosin and Ras related protein Rap-1A as potential new markers of active MS disease. A more complete description of cerebrovascular endothelial biomarkers and mediators in MS pathogenesis and how they are regulated by inflammatory cytokines and beta interferons may lead to the development of more effective therapies and more accurate diagnostic markers in MS. PMID- 17873363 TI - Neuronal conditioning medium and nerve growth factor induce neuronal differentiation of collagen-adherent progenitors derived from human umbilical cord blood. AB - The aim of the study was to isolate and characterize a population of neuronal progenitors in the human umbilical cord blood (HUCB) mononuclear cell (MNC) fraction, for in vitro manipulation towards neuronal differentiation. Selection of the HUCB neuronal progenitors (HUCBNPs) was based on the neuronal prerequisite for adherence to collagen. Populations of collagen-adherent, nestin-positive (94.8+/-2.9%) progenitors expressing alpha1/2 integrin receptors, as revealed by Western blot and adhesion assay using selective antagonists, were isolated and survived for more than 14 days. In vitro differentiation of the HUCBNPs was achieved by treatment with 10% human SH-SY5Y neuroblastoma cell-conditioning media (CM) supplemented with 10 ng/ml nerve growth factor (NGF). Some 83+/-8.2% of the surviving progenitors acquired a neuronal-like morphology, expressed by cellular outgrowths of different lengths. About 35+/-6% of the HUCBNPs had long outgrowths with a length/cell diameter ratio greater than 2, typical of developing neurons. The majority of these progenitors, analyzed by immunocytochemistry and/or RT-PCR, expressed common neuronal markers such as microtubule-associated protein 2 (MAP-2; 98.5+/-2%), neurotrophin receptor (TrkA; 98.5+/-0.06%), neurofillament-160 (NF-160; 94.2+/-1%), beta-tubulin III (89.8+/ 4.2%) and neuron specific enolase (NSE). Combined CM and NGF treatment induced constitutive activation of the mitogen-activated protein kinases ERK2 (36-fold vs control), p38alpha (nine-fold vs control) and p38beta (23-fold vs control), most likely related to survival and/or differentiation. The results point to operationally defined conditions for activating neuronal differentiation of HUCBNPs ex vivo and emphasize the crucial role of neuronal CM and NGF in this process. PMID- 17873364 TI - Long-term effects of JL 13, a potential atypical antipsychotic, on ionotropic glutamate receptors. AB - Changes in ionotropic glutamate (Glu) N-methyl-d-aspartic acid (NMDA), and 2 amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptors in rat forebrain regions were autoradiographically quantified after continuous infusion of JL 13 [(5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3-b][1,5]benzoxazepine fumarate] for 28 days using osmotic minipumps, and compared to the effects of representative typical (haloperidol) and atypical (clozapine, olanzapine, and risperidone) antipsychotic drugs from previous studies. Similar to other atypical and not typical antipsychotics, JL 13 decreased labeling of NMDA receptors in medial and lateral caudate-putamen (CPu; by 40%). These findings indicate that down-regulation of NMDA receptors by JL 13 and other atypical antipsychotic agents in CPu may contribute to their low risk of extrapyramidal side effects. In addition, and similar to olanzapine and risperidone, JL 13 increased AMPA receptor binding in CPu (by 42%). Changes in AMPA receptors may contribute to psychopharmacological properties of JL 13 and other atypical agents. Similar to clozapine, JL 13 did not alter levels of NMDA and AMPA receptors in hippocampus and entorhinal cortex. Long-term effects of JL 13 on ionotropic Glu receptors, as well as on other dopamine and serotonin receptors, support the atypical antipsychotic profile of this novel agent. PMID- 17873365 TI - Effect of peripheral axotomy on gene expression of NIDD in rat neural tissues. AB - Peripheral nerve lesion-induced production of neuronal nitric oxide synthase (nNOS) was implicated to influence a range of postaxotomy processes necessary for neuronal survival and nerve regeneration (Zochodne et al., Neuroscience, 91:1515 1527, 1999; Keilhoff et al., Journal of Chemical Neuroanatomy, 24:181-187, 2002, Nitric Oxide, 10:101-111, 2004). Protein-protein interactions represent an important mechanism in the control of NOS spatial distribution or activity (Alderton et al., Biochemical Journal, 357:593-615, 2001; Dedio et al., FASEB Journal, 15:79-89, 2001; Zimmermann et al., Proceedings of the National Academy of Sciences, 99:17167-17172, 2002). As one of the nNOS-binding proteins, nNOS interacting DHHC domain-containing protein with dendritic mRNA (NIDD) has recently been identified to increase nNOS enzyme activity by targeting nNOS to the synaptic plasma membrane in a postsynaptic density protein 95/discs large/zona occlusens-1 domain dependent manner (Saitoh et al., Journal of Biological Chemistry, 279:29461-29468, 2004). In this paper, we established a rat model with peripheral axotomy to investigate the gene expression patterns of NIDD in neural tissues using TaqMan quantitative real-time polymerase chain reaction and in situ hybridization combined with immunofluorescence. It revealed that NIDD mRNA was upregulated after sciatic nerve transection with the similar expressing styles as that of the nNOS in the injured nerves, corresponding dorsal root ganglia, and lumbar spinal cord. These findings imply that NIDD may be involved in the different pathological conditions including nerve regeneration, neuron loss or survival, and even pain process, possibly via regulating the enzyme nNOS activity. PMID- 17873366 TI - Lipopolysaccharide-induced upregulation of tumor necrosis factor-alpha (TNF alpha) and TNF receptors in rat sciatic nerve. AB - The proinflammatory and lipopolysaccharide (LPS)-inducible cytokine tumor necrosis factor alpha (TNF-alpha) has been shown to enhance primary sensory nociceptive signaling. However, the precise cellular sites of TNF-alpha and TNF receptors synthesis are still a matter of controversy. Therefore, we focused our study on TNF-alpha, TNFR1, and TNFR2 protein synthesis and expression patterns in sciatic nerve of controls and rats under systemic challenge with LPS. The enzyme linked immunosorbent (ELISA) assay showed that the protein level of TNF-alpha reached peak at 6 h. Double immunofluorescence revealed that LPS-induced expression of TNF-alpha exclusively located in a subpopulation of Schwann cells, endothelial cells, and macrophages, which increased at late time point in the rat sciatic nerve. Positive staining of TNF receptors were also found in Schwann cells and a few endothelial cells. These observations have demonstrated the production of this proinflammatory cytokine by peripheral nerve glia especially Schwann cells. Synthesized TNF-alpha might directly act on peripheral nerve glia via TNF receptors, but the inherent mechanisms remain unknown. Further studies are needed to confirm the pathogenic role of tumor necrosis factor in the early stage of inflammation. PMID- 17873367 TI - Parkin disrupts the alpha-synuclein/dopamine transporter interaction: consequences toward dopamine-induced toxicity. AB - Parkinson's disease is characterized by progressive neuronal degeneration of dopaminergic neurons in the substantia nigra. Many factors are thought to contribute to the neuronal cell death that occurs in Parkinson's disease, including alpha-synuclein-mediated toxicity. Previously, we have reported that alpha-synuclein directly couples to the carboxyl tail of the dopamine transporter (DAT) and that the alpha-synuclein/DAT protein complex formation accelerates DAT mediated cellular dopamine (DA) uptake and DA-induced cellular apoptosis. In the present study, we report that parkin, an E2-dependent E3 protein ubiquitin ligase associated with recessive early onset Parkinson's disease, exerts a protective effect against DA-induced alpha-synuclein-dependent cell toxicity. Parkin impairs the alpha-synuclein/DAT coupling by interacting with the carboxyl-terminus of the DAT and blocks the alpha-synuclein-induced enhancement in both DAT cell surface expression and DAT-mediated DA uptake. Moreover, we have found that parkin protects against DA-induced cell toxicity in dopaminergic SK-N-SH cells. These findings will help identify the role of these proteins in the etiology and/or maintenance of Parkinson's disease. PMID- 17873368 TI - Effect of gabapentin on c-Fos expression in the CNS after paw surgery in rats. AB - Gabapentin (neurontin), a GABA analogue anticonvulsant has proven to be effective in anti-nociceptive activity as well as for the treatment of anxiety. Gabapentin (GBP) is well tolerated and shows very favorable side effects profile: The exact molecular mechanism of action of GBP to block postoperative pain and stress is not known. Therefore, to identify the functional neuroanatomical target sites of GBP in post-surgery as well as its effect on postsurgical process, we examined the effects of GBP on c-Fos expression in the supraspinal part of the central nervous system in rats. Using a well-validated rat model of surgical pain, we studied the neuroanatomical functional target sites of gabapentin after paw surgery. The effect of GBP was examined by means of c-Fos immunohistochemistry. A single intraperitoneal injection (i.p.) of GBP (150 mg/kg) or saline (control) was administered 20 min before surgical incision in the paw under anesthesia. Ninety minutes after surgical incision, the deeply anesthetized rats were perfused transcardially with 4% paraformaldehyde. Serial 40-microm-thick sections of whole brain (except spinal cord) were cut and processed by immunohistochemistry to locate and quantify the sites and number of neurons with c-Fos immunoreactivity. Detection of c-Fos protein was performed using the peroxidase-antiperoxidase detection protocol. Our present study demonstrated that compared to control, administration of GBP (150 mg/kg, i.p.) before paw surgery significantly (p < 0.01) attenuated the incision-induced c-Fos expression only in the paraventricular nucleus of the hypothalamus. In addition, GBP-induced increase in c-Fos expression was observed in the dorsal raphe (DRN) and in the nucleus raphe magnus. Present results indicate that GBP may differentially modulate c-Fos expression in surgical paw incision. Moreover, this study provides some clue to examine whether GBP exerts its action simultaneously through two separate pathways in post-surgery. PMID- 17873369 TI - Dynamic relationship between neurostimulation and N-acetylaspartate metabolism in the human visual cortex: evidence that NAA functions as a molecular water pump during visual stimulation. AB - N-acetyl-l-aspartic acid (NAA), an amino acid synthesized and stored primarily in neurons in the brain, has been proposed to be a molecular water pump (MWP) whose function is to rapidly remove water from neurons against a water gradient. In this communication, we describe the results of a functional (1)H proton magnetic resonance spectroscopy (fMRS) study, and provide evidence that in the human visual cortex, over a 10-min period of visual stimulation, there are stimulation induced graded changes in the NAA MRS signal from that of a preceding 10-min baseline period with a decline in the NAA signal of 13.1% by the end of the 10 min stimulation period. Upon cessation of visual stimulation, the NAA signal gradually increases during a 10-min recovery period and once again approaches the baseline level. Because the NAA MRS signal reflects the NAA concentration, these changes indicate rapid focal changes in its concentration, and transient changes in its intercompartmental metabolism. These include its rates of synthesis and efflux from neurons and its hydrolysis by oligodendrocytes. During stimulation, the apparent rate of NAA efflux and hydrolysis increased 14.2 times, from 0.55 to 7.8 micromol g(-1) h(-1). During recovery, the apparent rate of synthesis increased 13.3 times, from 0.55 to 7.3 micromol g(-1) h(-1). The decline in the NAA signal during stimulation suggests that a rapid increase in the rate of NAA obligated water release to extracellular fluid (ECF) is the initial and seminal event in response to neurostimulation. It is concluded that the NAA metabolic cycle in the visual cortex is intimately linked to rates of neuronal signaling, and that the functional cycle of NAA is associated with its release to ECF, thus supporting the hypothesis that an important function of the NAA metabolic cycle is that of an efflux MWP. PMID- 17873370 TI - Times of change, times of growth. PMID- 17873371 TI - MorphML: level 1 of the NeuroML standards for neuronal morphology data and model specification. AB - Quantitative neuroanatomical data are important for the study of many areas of neuroscience, and the complexity of problems associated with neuronal structure requires that research from multiple groups across many disciplines be combined. However, existing neuron-tracing systems, simulation environments, and tools for the visualization and analysis of neuronal morphology data use a variety of data formats, making it difficult to exchange data in a readily usable way. The NeuroML project was initiated to address these issues, and here we describe an extensible markup language standard, MorphML, which defines a common data format for neuronal morphology data and associated metadata to facilitate data and model exchange, database creation, model publication, and data archiving. We describe the elements of the standard in detail and outline the mappings between this format and those used by a number of popular applications for reconstruction, simulation, and visualization of neuronal morphology. PMID- 17873372 TI - OdorMapComparer: an application for quantitative analyses and comparisons of fMRI brain odor maps. AB - Brain odor maps are reconstructed flat images that describe the spatial activity patterns in the glomerular layer of the olfactory bulbs in animals exposed to different odor stimuli. We have developed a software application, OdorMapComparer, to carry out quantitative analyses and comparisons of the fMRI odor maps. This application is an open-source window program that first loads two odor map images being compared. It allows image transformations including scaling, flipping, rotating, and warping so that the two images can be appropriately aligned to each other. It performs simple subtraction, addition, and average of signals in the two images. It also provides comparative statistics including the normalized correlation (NC) and spatial correlation coefficient. Experimental studies showed that the rodent fMRI odor maps for aliphatic aldehydes displayed spatial activity patterns that are similar in gross outlines but somewhat different in specific subregions. Analyses with OdorMapComparer indicate that the similarity between odor maps decreases with increasing difference in the length of carbon chains. For example, the map of butanal is more closely related to that of pentanal (with a NC = 0.617) than to that of octanal (NC = 0.082), which is consistent with animal behavioral studies. The study also indicates that fMRI odor maps are statistically odor-specific and repeatable across both the intra- and intersubject trials. OdorMapComparer thus provides a tool for quantitative, statistical analyses and comparisons of fMRI odor maps in a fashion that is integrated with the overall odor mapping techniques. PMID- 17873373 TI - Neuronal apoptosis revealed by genomic analysis: integrating gene expression profiles with functional information. AB - Apoptosis is a key physiological response that occurs during development of the nervous system, resulting in the death of nearly half of the embryonic neuronal population. Aberrant apoptotic mechanisms are thought to contribute significantly to many neurological disorders including Alzheimer's disease. Although many experiments in the past have demonstrated the requirement of de novo gene expression during neuronal apoptosis, the complete spectrum of genes involved in distinct temporal domains is mostly unknown. To begin a comprehensive survey of the gene-based molecular mechanisms that underlie neuronal apoptosis, we have used the unprecedented experimental opportunities that genome sequences and the development of DNA microarray technology now provide to perform genome-wide expression analysis in different paradigms of neuronal apoptosis. In order to extract knowledge from gene expression information we have developed new informatics applications that enable clustering methods based on semantic characteristics, such as gene ontologies. This review will highlight the use of a genomic approach to identify the molecular program underlying neuronal apoptosis and illustrate how a semantic clustering method can be useful to extract more knowledge from microarray data. PMID- 17873374 TI - Interoperability of neuroscience modeling software: current status and future directions. AB - Neuroscience increasingly uses computational models to assist in the exploration and interpretation of complex phenomena. As a result, considerable effort is invested in the development of software tools and technologies for numerical simulations and for the creation and publication of models. The diversity of related tools leads to the duplication of effort and hinders model reuse. Development practices and technologies that support interoperability between software systems therefore play an important role in making the modeling process more efficient and in ensuring that published models can be reliably and easily reused. Various forms of interoperability are possible including the development of portable model description standards, the adoption of common simulation languages or the use of standardized middleware. Each of these approaches finds applications within the broad range of current modeling activity. However more effort is required in many areas to enable new scientific questions to be addressed. Here we present the conclusions of the "Neuro-IT Interoperability of Simulators" workshop, held at the 11th computational neuroscience meeting in Edinburgh ( July 19-20 2006; http://www.cnsorg.org ). We assess the current state of interoperability of neural simulation software and explore the future directions that will enable the field to advance. PMID- 17873375 TI - NIH Conference on Knowledge Environments for Biomedical Research (December 11-12, 2006). PMID- 17873376 TI - Cancer and stem cell signaling: a guide to preventive and therapeutic strategies for cancer stem cells. PMID- 17873377 TI - Signaling pathways in cancer and embryonic stem cells. AB - Cancer cells have the ability to divide indefinitely and spread to different parts of the body during metastasis. Embryonic stem cells can self-renew and, through differentiation to somatic cells, provide the building blocks of the human body. Embryonic stem cells offer tremendous opportunities for regenerative medicine and serve as an excellent model system to study early human development. Many of the molecular mechanism underlying tumorigenesis in cancer and self renewal in stem cells have been elucidated in the past decade. Here we present a systematic analysis of seven major signaling pathways implicated in both cancer and stem cells. We present on overview of the JAK/STAT, Notch, MAPK/ERK, PI3K/AKT, NF-kB, Wnt and TGF-beta pathways and analyze their activation status in the context of cancer and stem cells. We focus on their role in stem cell self renewal and development and identify key molecules, whose aberrant expression has been associated with malignant phenotypes. We conclude by presenting a map of the signaling networks involved in cancer and embryonic stem cells. PMID- 17873378 TI - The Wnt signal transduction pathway in stem cells and cancer cells: influence on cellular invasion. AB - The regulative network conducting adult stem cells in endogenous tissue repair is of prime interest for understanding organ regeneration as well as preventing degenerative and malignant diseases. One major signal transduction pathway which is involved in the control of these (patho)physiological processes is the Wnt pathway. Recent results obtained in our laboratories showed for the first time that canonical Wnt signaling is critically involved in the control of the migration/invasion behaviour of human mesenchymal stem cells (hMSC). In the first part of this review, we describe that the regenerative state is closely linked to the activation of the Wnt pathway. Central hallmarks of activated stem cells are recapitulated in a similar way also in cancer metastasis, where the acquisition of an invasive cancer stem cell phenotype is associated with the induction of Wnt mediated epithelial to mesenchymal transition (EMT). In the second part, the influence of proinflammatory cytokines such as transforming growth factor (TGF )beta1, interleukin (Il-)1beta, and tumor necrosis factor (TNF-)alpha is discussed with regard to the invasive characteristics of hMSC. In this context, special attention has been paid on the role of matrix metalloproteinases (MMPs), such as MMP-2, MMP-9 and membrane type 1 (MT1)-MMP, as well as on the tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2. Putative cross-talks between different signal transduction pathways that may amplify the invasive capacity of this stem cell population are also discussed. Finally, the consequences towards future drug-mediated therapeutical modifications of Wnt signaling in stem cells and tumor cells are highlighted. PMID- 17873379 TI - Networking of WNT, FGF, Notch, BMP, and Hedgehog signaling pathways during carcinogenesis. AB - The biological functions of some orthologs within the human genome and model animal genomes are evolutionarily conserved, but those of others are divergent due to protein evolution and promoter evolution. Because WNT signaling molecules play key roles during embryogenesis, tissue regeneration and carcinogenesis, the author's group has carried out a human WNT-ome project for the comprehensive characterization of human genes encoding WNT signaling molecules. From 1996 to 2002, we cloned and characterized WNT2B/WNT13, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT9A/WNT14, WNT9B/WNT14B, WNT10A, WNT10B, WNT11, FZD1, FZD2, FZD3, FZD4, FZD5, FZD6, FZD7, FZD8, FZD10, FRAT1, FRAT2, NKD1, NKD2, VANGL1, RHOU/ARHU, RHOV/ARHV, GIPC2, GIPC3, FBXW11/betaTRCP2, SOX17, TCF7L1/TCF3, and established a cDNA-PCR system for snap-shot and dynamic analyses on the WNT-transcriptome. In 2003, we identified and characterized PRICKLE1, PRICKLE2, DACT1/DAPPER1, DACT2/DAPPER2, DAAM2, and BCL9L. After completion of the human WNT-ome project, we have been working on the stem cell signaling network. WNT signals are transduced to beta-catenin, NLK, NFAT, PKC, JNK and RhoA signaling cascades. FGF20, JAG1 and DKK1 are target genes of the WNT-beta-catenin signaling cascade. Cross-talk of WNT and FGF signaling pathways potentiates beta-catenin and NFAT signaling cascades. BMP signals induce IHH upregulation in co-operation with RUNX. Hedgehog signals induce upregulation of SFRP1, JAG2 and FOXL1, and then FOXL1 induces BMP4 upregulation. The balance between WNT-FGF-Notch and BMP Hedgehog signaling networks is important for the maintenance of homoestasis among stem and progenitor cells. Disruption of the stem cell signaling network results in pathological conditions, such as congenital diseases and cancer. PMID- 17873380 TI - Stem cells and TCF proteins: a role for beta-catenin--independent functions. AB - The Wnt signal transduction pathway has been shown to stimulate stem cell self renewal and has been shown to cause cancer in humans. One interesting aspect of Wnt signaling is that it utilizes downstream DNA-binding transcription factors, called Tcf proteins, which can activate transcription of target genes in the presence of a Wnt signal and repress the expression of target genes in the absence of a Wnt signal. Since Tcf proteins are present in Wnt-stimulated and unstimulated stem cells, understanding how Tcf proteins regulate target gene expression in each state offers the potential to understand how stem cells regulate their self-renewal, differentiation, and proliferation. In this article, we will review recent work elucidating the roles Tcf-protein interactions in the context of stem cells and cancer. PMID- 17873381 TI - The stem cell identity of testicular cancer. AB - Testicular germ cell tumors account for 1% of all cancers, and are the most common malignancies to affect males between the ages of 15 and 34. Understanding the pathogenesis of testis cancer has been challenging because the molecular and cellular events that result in the formation of germ cell tumors are hypothesized to occur during human fetal development. In this review, the molecular pathways involved in human testis cancer will be presented based on our research in human embryonic stem cells (hESCs), and also research using animal models. Testis germ cell tumors are unique in that the normal germ cell from which the tumor is derived has distinct stem cell characteristics that are shared with pluripotent hESCs. In particular, normal fetal germ cells express the core pluripotent transcription factors NANOG, SOX2 and OCT4. In contrast to hESCs, the germ line is not pluripotent. As a result, germ cell tumorigenesis may arise from loss of germ line-specific inhibitors which in normal germ cells prevent overt pluripotency and self-renewal and when absent in abnormal germ cells, result in the conversion to germ line cancer stem cells. At the conclusion of this review, a model for the molecular events involved in germ cell tumor formation and the relationship between germ cell tumorigenesis and stem cell biology will be presented. PMID- 17873383 TI - Commentary: Facing up to the feasibility of ANT-OAR. PMID- 17873382 TI - The flawed scientific basis of the altered nuclear transfer-oocyte assisted reprogramming (ANT-OAR) proposal. AB - First put forth in June 2005, the altered nuclear transfer-oocyte assisted reprogramming (ANT-OAR) proposal has been promoted as an ethically-acceptable alternative to the embryo-destructive methods now used to obtain embryonic stem cells. According to its proponents, the goal of ANT-OAR is to use the cloning process to create a pluripotent stem cell. This would be achieved through overexpression of the transcription factor Nanog (or a hypothetical substitute) both in the enucleated egg cell and in the somatic cell prior to transfer of its nucleus. Although the ethical acceptability of ANT-OAR has been publicly debated, its scientific feasibility has not. This paper aims to help rectify this situation. It argues that ANT-OAR, as currently conceived, cannot realistically work. It presents evidence from the scientific literature showing that Nanog cannot single-handedly establish pluripotency in cells, but rather works together with a network of other transcription factors to maintain pluripotency. It argues that ANT-OAR is based on a flawed understanding of stem cell biology, and emphasizes that, in this debate about embryonic stem cells, scientists must strive to accurately and realistically assess the feasibility of the embryo research strategies they propose. PMID- 17873384 TI - Exploiting the convergence of embryonic and tumorigenic signaling pathways to develop new therapeutic targets. AB - As our understanding of embryonic stem cell biology becomes more sophisticated, the similarities between multipotent cancer cells and these totipotent precursors are increasingly striking. Both multipotent cancer cells and embryonic stem cells possess the ability to self-renew, epigenetically alter their neighboring cellular architecture, and populate a tissue mass with a phenotypically heterogeneous composition of cells. While the molecular signature of these cell types continues to be elucidated, new insights are emerging related to the convergence of embryonic and tumorigenic signaling pathways. Understanding the molecular underpinnings of these two stem cell phenotypes may lead to new therapeutic targets for the elusive cancer cell. While still in its infancy, the potential of adapting embryonic stem cells, and more specifically the factors they produce, is enormous for clinical application. Here we outline evidence that demonstrates the inductive influence of embryonic stem cells and their microenvironment to reprogram cancer cells to exhibit a more benign phenotype, with profound implications for differentiation therapy. PMID- 17873385 TI - Stem cell origin of death-from-cancer phenotypes of human prostate and breast cancers. AB - In clinical terms, all human cancers diagnosed in individuals can be divided in two major categories: malignant tumors that will be cured with the existing cancer therapies and tumors that have therapy-resistant phenotypes and will return after initial treatment as incurable metastatic disease. These tumors manifesting clinically lethal death-from-cancer phenotypes represent the most formidable challenge of experimental, translational, and clinical cancer research. Clinical genomics data demonstrate that gene expression signatures associated with the "stemness" state of a cell are informative as molecular predictors of cancer therapy outcome and can help to identify cancer patients with therapy-resistant tumors. Here, we present experimental and clinical evidence in support of the BMI1 pathway rule indicating a genetic link between the stemness state and therapy-resistant death-from-cancer phenotypes. Our analysis demonstrates that therapy-resistant and therapy-responsive cancer phenotypes manifest distinct patterns of association with stemness/differentiation pathways, suggesting that therapy-resistant and therapy responsive tumors develop within genetically distinct stemness/differentiation programs. These differences can be exploited for development of prognostic and therapy selection genetic tests utilizing a microarray-based cancer therapy outcome predictor algorithm. One of the major regulatory pathways manifesting distinct patterns of association with therapy-resistant and therapy-responsive cancer phenotypes is the Polycomb group proteins chromatin silencing pathway. PMID- 17873386 TI - Stem cell chronicles: autobiographies within genomes. AB - Human stem cell studies are difficult because many of the powerful experimental approaches that mark and follow stem cells and their progeny are impractical. Moreover, humans are long-lived, and it would literally take a lifetime to follow stem cell fates prospectively. Considering these hurdles, an ideal method would not require prior experimental manipulations but still allow "observations" of human stem cells from birth to death. The purpose of this review is to outline how histories or fates are likely to be surreptitiously recorded within somatic cell genomes by replication errors (molecular clock hypothesis). It may be possible to reconstruct stem cell lifetimes by measuring the random somatic changes that accumulate within their genomes, or the genomes of their more-easy to-identify progeny. PMID- 17873387 TI - Significance of zinc in nephrotoxicity of contrast media used in imaging diagnostics of the cardiovascular system. AB - Nephrotoxicity is an undesirable reaction of contrast media used in X-ray or magnetic resonance diagnostics. In addition to a direct toxic effect on renal tubules, the hemodynamic factor is considered to be the main cause of kidney damage and malfunction. The factors that increase the probability of a nephrotoxic effect of contrast media include oldage, diabetes, arterial hypertension, circulatory system insufficiency, neoplastic diseases, and prior kidney damage. Decreased serum zinc is observed in all those conditions. In this article, the influence of contrast media on zinc homeostasis and the possibility of a nephrotoxic reaction caused by these agents is discussed. PMID- 17873388 TI - Zinc inhibits nonheme iron bioavailability in humans. AB - There is increasing concern about potential negative interactions in combined iron and zinc supplementation. The aim of the present study was to determine the dose-response effect of zinc, given as a solution, on iron bioavailability. Twenty-two healthy adult women were selected to participate in the study. Iron, with or without zinc was given as an aqueous solution on d 1,2,14, and 15 of the study. Iron bioavailability was measured on the basis of erythrocyte incorporation of 55Fe or 59Fe 14 d after administration. Subjects received 0.5 mg of iron together with graded zinc concentrations (0-11.71 mg). No significant effect of zinc on iron absorption was found at Zn:Fe molar ratios up to 2:1. At 5:1,10:1, and 20:1 molar ratios, a dose-dependent inhibitory effect on iron absorption was observed (28-40% of iron absorption inhibition; one-way repeated measures ANOVA, F=4.48, p=0.02). In conclusion, zinc administration combined with iron in an aqueous solution leads to the inhibition of iron bioavailability, which occurs in a dose-dependent way. This negative interaction should be considered for supplementation programs with both microminerals. PMID- 17873389 TI - Zinc ions efflux from lymphocytes in vitro in the presence of a calcium and magnesium ionic environment and its changes following administration of verapamil. AB - The total and ouabain-dependent rate constants of efflux of zinc (Zn) ions from lymphocytes isolated from healthy subjects were measured in vitro in an environment containing calcium (Ca) and magnesium (Mg) ions. Both the total (ERCt Zn) and ouabain-dependent (ERCos-Zn) rate constants were higher in the presence of Mg2+, with the the oubain-dependent efflux significantly different 0.29+/-0.07 vs 0.13+/-0.02 with and without Mg2+, respectively (p<0.001). After the addition of verapamil, an increase of ERCE-Zn was observed in both ionic environments and was higher and statistically significant in the presence of Mg2+: 1.94+/-0.64 vs 2.97+/-1.16 (p<0.025). These results suggest that verapamil has an enhancing effect on Zn efflux from isolated lymphocytes, suggesting that calcium channel blockers might result in better Zn homeostatic regulation in diseases of the cardiovascular system. PMID- 17873390 TI - Age-related changes of elements in thoracic and abdominal aortas and coronary, common carotid, pulmonary, splenic, common iliac, and uterine arteries and relationships in elements among their arteries. AB - To elucidate whether the accumulation of elements occurred simultaneously in the various arteries with aging, the authors investigated age-related changes of elements in the eight arteries, such as the thoracic and abdominal aortas and the coronary, common carotid, pulmonary, splenic, common iliac, and uterine arteries, and the relationships in the element contents among their arteries. After ordinary dissection by medical students was finished, the thoracic and abdominal aortas and the coronary, common carotid, pulmonary, splenic, common iliac, and uterine arteries were resected from the subjects, who ranged in age from 58 to 94 yr. The element contents were analyzed by inductively coupled plasma-atomic emission spectrometry. It was found that the accumulation of Ca was the highest in the common iliac artery and decreased in the order of the uterine artery, abdominal aorta, coronary artery, thoracic aorta, splenic artery, common carotid artery, and pulmonary artery. Regarding the relationships in the element contents among the eight arteries, it was found that there were significant direct correlations in the contents of Ca, P, Mg, Zn, Fe, and Na between the coronary and splenic arteries, and there were significant correlations in the contents of Ca, P, and Mg between the abdominal aorta and pulmonary artery. PMID- 17873391 TI - Role of zinc in regulation of arterial blood pressure and in the etiopathogenesis of arterial hypertension. AB - Increased gastrointestinal absorption and urinary excretion of zinc has been confirmed in experimental and clinical studies on primary arterial hypertension as a result from changes of intracellular and extracellular zinc content. In arterial hypertension, the levels of zinc in serum, lymphocyte, and bone decrease while increasing in heart, erythrocytes, kidney, liver, suprarenal glands and spleen. These changes result in the loss of zinc homeostasis that leads to various degrees of deficiency, not entirely compensated by nutritional factors or increased absorption in the gastrointestinal tract. Loss of zinc homeostasis can be both cause and effect of high blood pressure. In the present review, the role of zinc metabolism changes and its mechanisms in arterial hypertension are discussed. PMID- 17873392 TI - The influence of melatonin and N-acetylcysteine in delta-aminolevulinic acid and lead induced genotoxicity in lymphocytes in vitro. AB - As is well known from earlier studies, the genotoxic effect of lead exposure was partly attributed to the formation of the highly reactive oxygen metabolites (ROMs) in the blood. However, lead ions have no ability to generate ROMs. Therefore, the recently published studies paid more attention to the role of delta-aminolevulinic acid (ALA) accumulation in lead-induced DNA damage. If the above-mentioned assumptions were taken into consideration, it seemed a reasonable approach to study the possible protective effects of antioxidants against genotoxic effects of lead. According to our results, N-acetylcysteine (NAC) and melatonin (MEL) were able to reduce significantly (p<0.05) the lead- and ALA induced sister chromatid exchange frequencies in human lymphocytes in vitro. In spite of a relative reduction in the lead- and ALA-induced micronucleus formation in human lymphocytes, the reduction was not statistically significant (p>0.05). These results could be evaluated as supportive evidence for the hypothesis that increased antioxidant capacity of cells might fortify the efficiency of protective pathways against cytogenetic damage in lead exposure. PMID- 17873393 TI - Potential involvement of serine/threonine protein phosphatases in apoptosis of HepG2 cells during selenite treatment. AB - Selenium, an essential biological trace element present in both prokaryotic and eukaryotic cells, exerts its regulatory effect in a variety of cellular events, including cell growth, survival, and death. Selenium compounds have been shown in different cell lines to inhibit apoptosis by several mechanisms. Serine/threonine phosphatases (STPs) are potentially important in selenite-induced apoptosis because of their role in regulation of diverse set of cellular processes. In this study, the regulatory role of STPs in selenite-induced apoptosis has been implied by the use of two specific inhibitors: ocadaic acid and calyculin A. Our results show a decrease in cell density in HepG2 cells under selenite treatment. Resulting specific enzyme activities showed a concentration-dependent increase in all three phosphatase activities after 24 h in cells treated with 5 microM selenite and these activities decreased at 48 and 72 h. However, in cells treated with 10 microM selenite, PP2A and PP2B decreased at 48 h, whereas PP2C activity did not change at this dose. In cells treated with 25 microM, there was not a significant change in PP2C activity. These data suggest that the most specific response to selenite treatment was in PP2A and PP2B activities in a dose dependent manner. Our results with OA and Cal-A further support the view that PP1 and PP2A might act as negative regulators of growth. With these data, we have first demonstrated the role of serine/threonine protein phosphatases in the signaling pathway of selenite-induced apoptosis and resulting cytotoxicity. PMID- 17873394 TI - Effect of sodium selenosulfate on restoring activities of selenium-dependent enzymes and selenium retention compared with sodium selenite in vitro and in vivo. AB - Sodium selenosulfate has been extensively used as a precursor of selenide ions in the preparation of nano Se-containing compounds. Its biological properties remain completely unknown. Sodium selenosulfate and sodium selenite were added to the medium of HepG2 cells and administered intraperitoneally at a dose of 0.1 mg Se/kg body weight to selenium-deficient mice, respectively. Both of the selenium compounds could increase the activities of glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) in a dose-dependent manner in cells and efficiently restore selenium retention and activities of GPx and TrxR in mice. All of the variables were in correlation with the Se supply. There was no distinction in elevating activities of GPx and TrxR between selenosulfate and selenite in vitro. After a 2-d supply of selenosulfate, the activity of GPx in the liver was 65% (p<0.001) and Se accumulations in the liver, kidney and blood were 64%, 86%, and 65%, respectively, of those treated with selenite (all p<0.01). With the 7-d selenosulfate supplementation, the activity of GPx in the kidney and activities of TrxR in the liver and kidney were 88%, 75%, and 78%, respectively, of those treated with selenite (all p<0.01); Se retentions in the liver and kidney were 85% and 93%, respectively of those supplemented with selenite (both p<0.01). These facts indicated that selenosulfate could be absorbed and utilized in the biological system. No difference in vitro demonstrated that selenosulfate could be absorbed and generate reduced selenide as efficiently as selenite. The differences between the two compounds in vivo were the result of other factors that affected selenosulfate utilization in tissues. PMID- 17873395 TI - Ytterbium and trace element distribution in brain and organic tissues of offspring rats after prenatal and postnatal exposure to ytterbium. AB - Lanthanides, because of their diversified physical and chemical effects, have been widely used in a number of fields. As a result, more and more lanthanides are entering the environment and eventually accumulating in the human body. Previous studies indicate that the impact of lanthanides on brain function cannot be neglected. Although neurological studies of trace elements are of paramount importance, up to now, little data are provided regarding the status of micronutritional elements in rats after prenatal and long-term exposure to lanthanide. The aim of this study is to determine the ytterbium (Yb) and trace elements distribution in brain and organic tissues of offspring rats after prenatal and long-term exposure to Yb. Wistar rats were exposed to Yb through oral administration at 0,0.1, 2, and 40 mg Yb/kg concentrations from gestation day 0 through 5 mo of age. Concentrations of Yb and other elements (Mg, Ca, Fe, Cu, Mn, and Zn) in the serum, liver, femur, and brain regions (cerebral cortex, hippocampus, cerebellum, and the rest) of offspring rats at the age of 0 d, 25 d, and 5 mo were analyzed by inductively coupled plasma-mass spectrometry. The accumulation of Yb in the brain, liver, and femur is observed; moreover, the levels of Fe, Cu, Mn, Zn, Ca, and Mg in the brain and organic tissues of offspring rats are also altered after Yb exposure. This disturbance of the homeostasis of trace elements might induce adverse effects on normal physiological functions of the brain and other organs. PMID- 17873396 TI - Effects of selenium and tellurium on the activity of selenoenzymes glutathione peroxidase and type I iodothyronine deiodinase, trace element thyroid level, and thyroid hormone status in rats. AB - Tellurium (Te) and selenium (Se) belong chemically to the VIa group of elements. Se represents an essential element closely related to thyroid function. Te has growing application in industrial processes. Little is known about the Te biological activity, particularly with respect to potential chemical interactions with Se-containing components in the organism. In this study, female Wistar rats (body weight: 115-120 g) received sodium selenite pentahydrate (10 mg/L) or sodium tellurite (9.4 mg/L) in drinking water for 6 wk. Additional groups of rats received their combination with zinc sulfate heptahydrate (515 mg/L). The stimulation of 5'-DI-I activity due to selenite (to 158%, p<0.01) or tellurite treatment (to 197%, p<0.01) was seen; however, no effect on glutathione peroxidase was demonstrated in this experiment. An elevation of T4, T3, and rT3 serum levels was measured in the Se+Te-treated group; T4 and rT3 levels were elevated in the Te+Zn-treated group. Te accumulates in the thyroid gland and influences the zinc thyroid level. Te treatment alone and in combination with Se or Zn decreased the iodine thyroid concentration to 65-70% of the control value. Further studies are needed to clarify the nature and effects of these events. PMID- 17873397 TI - Analysis of tissue cadmium distribution in chronic cadmium-exposed mice using in air micro-PIXE. AB - This study undertook the analysis of tissue cadmium (Cd) distribution using in air micro-particle-induced X-ray emission (PIXE) and the examination of the involvement of metal ions in parenteral Cd toxicity. A mouse was injected intraperitoneally with 3 mg/kg body weight of CdCl2 thrice weekly. After 27 wk, the liver and kidney were excised and fixed in 10% formalin solution for 4 h and then embedded in paraffin. Thin paraffin sections were used to analyze trace elements with in-air micro-PIXE and to examine metallothionein protein and histological changes. Cd distribution was determined by micro-PIXE in the liver and renal cortex of the Cd-exposed mouse, and the net Cd count was higher in the liver than in the renal cortex. The net iron (Fe) count was higher in the liver of the Cd-exposed mouse compared to the control, and an opposite tendency was observed in the renal cortex. Wide cellular Cd distribution was demonstrated in the liver and renal cortex of the chronic Cd-exposed mouse compared to the control. Metallothionein staining was increased by chronic exposure to Cd both in the liver and kidney, and nephrotoxicity was more apparent than hepatotoxicity. The modification of tissue Fe and calcium distribution by an intraperitoneal injection of Cd might be involved in Cd-induced toxicity. PMID- 17873398 TI - Decreased beta-adrenoceptor chronotropic response in selenium-deficient mice: negative crosstalk between iNOS activity and cAMP accumulation. AB - With the aim to study if selenium (Se) deficiency affects the basal frequency and cardiac response to isoproterenol (ISO), mice were fed a Se-deficient diet (Se-) or the same diet supplemented with 0.2 ppm Se as sodium selenite (Se+) for 4 wk. Atria frequency, cyclic AMP (cAMP) accumulation, nitric oxide synthase (NOS) activity, and beta-adrenoceptor-binding assay were then examined. Results showed that Se-mice have both a reduction in atria frequency as well as in cAMP content but higher NOS activity levels either at basal or after ISO stimulation. These differences were suppressed by feeding Se-mice with a Se-supplemented diet for 1 wk or by inhibition of inducible nitric oxide synthase (iNOS). Alterations observed after ISO stimulation in atria of Se-mice were not related to a beta adrenoceptor expression modification because specific radioligand-binding parameters in cardiac membranes from Se-mice and Se+ mice were similar. The reduced response on rate and cAMP in atria from Se-mice to direct adenylate cyclase (AC) stimulation by forskolin and the shifted upward levels present in 2 amino-4-methylpyridine-treated Se-mice is in agreement with a negative crosstalk between iNOS activity and AC activity in Se-mice. PMID- 17873399 TI - Potential of Vinca rosea extracts in modulating trace element profile: a chemopreventive approach. AB - Diethylnitrosamine (DEN) was used as cancer-inducing agent in the experimental animals. Vinca rosea extract was supplemented with the drinking water as a chemopreventive agent. After 4 wk of treatment, animals were sacrificed and livers were excised. Nuclei and mitochondria were separated by differential centrifugation. The proton-induced X-ray emission technique has been used as the analytical method. Elemental analysis were performed for whole liver, nuclei, and mitochondria.V. rosea plant parts were also analyzed for elemental contents. Treatment with DEN caused an increase of Ni, Zn, and Cr levels in the whole liver and nuclei. There is an increase in Fe concentration in the liver, although the level decreased in mitochondria. The concentrations of Br and Ca were unchanged in the liver as a whole, but there were substantial increases of Br in nuclei and mitochondria, whereas Ca levels depleted drastically in these two organelles. Vinca extracts were effective in reverting the changes in the elemental concentration in the hepatic tissue as a whole, but were not that effective at subcellular levels. PMID- 17873402 TI - Common mechanisms for the regulation of B cell differentiation and transformation by the transcriptional repressor protein BCL-6. AB - The BCL-6 transcriptional repressor protein is a critical regulator of normal B cell differentiation and BCL-6 has recently been shown to act as an oncogene in several mouse model systems. The molecular pathways by which BCL-6 regulates B cell differentiation and also promotes the transformation of primary B cells are undoubtedly related; however, these pathways are poorly understood. The commonly accepted model for BCL-6 function in B cells is that BCL-6 inhibits the terminal differentiation of activated B cells into plasma cells and that deregulation of BCL-6 expression leads to an inhibition of terminal differentiation and continued proliferation. BCL-6 induces a germinal-center phenotype in primary B cells by unknown mechanisms, and can reverse the terminal differentiation of plasma cell tumor lines. BCL-6 can promote the immortalization of primary B cells and can augment telomerase activity. The role of the vast majority of BCL-6 target genes and interacting proteins in normal B cell differentiation and B cell transformation is essentially unresolved and is an important area for future investigation. PMID- 17873401 TI - Anaphylatoxins: their role in bacterial infection and inflammation. AB - Activation of the complement system plays a crucial role in the pathogenesis of infection and inflammation. Especially the complement activation products C3a and C5a, known as the anaphylatoxins, are potent proinflammatory mediators. In addition to their evident role in innate immunity, it is clear that the anaphylatoxins also play a role in regulation of adaptive immune responses. The anaphylatoxins play a role in a variety of infectious and inflammatory diseases like sepsis, ischemia-reperfusion injury, immune complex diseases, and hypersensitivity diseases like asthma. In this review we discuss the role of anaphylatoxins in infection and inflammation. Furthermore, we focus on bacterial complement evasion strategies that can provide tools for further research on pathogenesis of infectious diseases and a better understanding of the role of complement and anaphylatoxins in infection and inflammation. PMID- 17873404 TI - Relationship between diseases accompanied by tissue destruction and granulocytes with surface adrenergic receptors. AB - It is well-known that physiological phenomena and certain diseases, including neonatal granulocytosis, age-associated granulocytosis, periodontitis, pancreatitis, Crohn's disease, ulcerative colitis, hemorrhoids, endometriosis, and NSADs-enteritis, are accompanied by tissue destruction and granulocytosis. We investigated what is a key factor connecting tissue destruction and granulocytosis, attention being focused on adrenergic receptors on granulocytes and stress-induced sympathetic nerve stimulation. If we introduce the concept that "granulocytosis and subsequent tissue destruction are induced by sympathetic nerve stimulation," the mechanisms underlying many physiological phenomena and the etiology of several uncurable diseases in humans can be clearly understood. PMID- 17873405 TI - Comparison of Alexa Fluor and CyDye for practical DNA microarray use. AB - Microarrays are a powerful tool for comparison and understanding of gene expression levels in healthy and diseased states. The method relies upon the assumption that signals from microarray features are a reflection of relative gene expression levels of the cell types under investigation. It has previously been reported that the classical fluorescent dyes used for microarray technology, Cy3 and Cy5, are not ideal due to the decreased stability and fluorescence intensity of the Cy5 dye relative to the Cy3, such that dye bias is an accepted phenomena necessitating dye swap experimental protocols and analysis of differential dye affects. The incentive to find new fluorophores is based on alleviating the problem of dye bias through synonymous performance between counterpart dyes. Alexa Fluor 555 and Alexa Fluor 647 are increasingly promoted as replacements for CyDye in microarray experiments. Performance relates to the molecular and steric similarities, which will vary for each new pair of dyes as well as the spectral integrity for the specific application required. Comparative analysis of the performance of these two competitive dye pairs in practical microarray applications is warranted towards this end. The findings of our study showed that both dye pairs were comparable but that conventional CyDye resulted in significantly higher signal intensities (P < 0.05) and signal minus background levels (P < 0.05) with no significant difference in background values (P > 0.05). This translated to greater levels of differential gene expression with CyDye than with the Alexa Fluor counterparts. However, CyDye fluorophores and in particular Cy5, were found to be less photostable over time and following repeated scans in microarray experiments. These results suggest that precautions against potential dye affects will continue to be necessary and that no one dye pair negates this need. PMID- 17873403 TI - T and B cell responses to HDM allergens and antigens. AB - House dust mites provide well-characterized proteins to study human responses to inhaled antigens. Even in the absence of allergy they induce a high frequency of T cell precursors. The healthy response manifests by T cell proliferation and Th1 cytokines with little antibody. Responses of allergic people include Th1 and Th2 cytokines and IgE, IgG1, and IgG4 antibodies. Regulatory cells limit effector responses in healthy people. About half the IgE and IgG antibodies bind the group 1 and 2 allergens and 30% bind the group 4, 5, and 7 allergens. Although HLA independent, the recognition of the group 1 allergen shows an immunodominant region and a T cell receptor bias. The major allergens are not produced in higher amounts than many of the poorly non-allergenic proteins. The non-allergenic mite ferritin antigen shows high T cell proliferative responses with mixed cytokine production. PMID- 17873406 TI - Gene delivery by lentivirus vectors. AB - The capacity to efficiently transduce nondividing cells, shuttle large genetic payloads, and maintain stable long-term transgene expression are attributes that have brought lentiviral vectors to the forefront of gene delivery vehicles for research and therapeutic applications in a clinical setting. Our discussion initiates with advances in lentiviral vector development and how these sophisticated lentiviral vectors reflect improvements in safety, regarding the prevention of replication competent lentiviruses (RCLs), vector mobilization, and insertional mutagenesis. Additionally, we describe conventional molecular regulatory systems to manage gene expression levels in a spatial and temporal fashion in the context of a lentiviral vector. State of the art technology for lentiviral vector production by transient transfection and packaging cell lines are explicitly presented with current practices used for concentration, purification, titering, and determining the safety of a vector stock. We summarize lentiviral vector applications that have received a great deal of attention in recent years including the generation of transgenic animals and the stable delivery of RNA interference molecules. Concluding remarks address some of the successes in preclinical animals, and the recent transition of lentiviral vectors to human clinical trials as therapy for a variety of infectious and genetic diseases. PMID- 17873407 TI - Microarray analysis: basic strategies for successful experiments. AB - Microarrays offer a powerful approach to the analysis of gene expression that can be used for a wide variety of experimental purposes. However, there are several types of microarray platforms that are available. In addition, microarray experiments are expensive and generate complicated data sets that can be difficult to interpret. Success with microarray approaches requires a sound experimental design and a coordinated and appropriate use of statistical tools. Here, the advantages and pitfalls of utilizing microarrays are discussed, as are practical strategies to help novice users succeed with this method that can empower them with the ability to assay changes in gene expression at the whole genome level. PMID- 17873408 TI - Co-expression of LKB1, MO25alpha and STRADalpha in bacteria yield the functional and active heterotrimeric complex. AB - The tumour suppressor LKB1 plays a critical role in cell proliferation, polarity and energy metabolism. LKB1 is a Ser/Thr protein kinase that is associated with STRAD and MO25 in vivo. Here, we describe the individual expression of the three components of the LKB1 complex using monocistronic vectors and their co expression using tricistronic vectors that were constructed from monocistronic vectors using a fully modular cloning approach. The data show that among the three individually expressed components of the LKB1 complex, only MO25alpha can be expressed in soluble form, whereas the other two, LKB1 and STRADalpha are found almost exclusively in inclusion bodies. However, using the tricistronic vector system, functional LKB1-MO25alpha-STRADalpha complex was expressed and purified from soluble extracts by sequential immobilized-metal affinity and heparin chromatography, as shown by Western blotting using specific antibodies. In size exclusion chromatography, MO25alpha and STRADalpha exactly co-elute with LKB1 with an apparent molecular weight of the heterotrimeric complex of 160 kDa. The specific activity in the peak fraction of the size exclusion chromatography was 250 U/mg at approximately 25% purity. As shown by autoradiography, LKB1 and STRADalpha, both strongly autophosphorylate in vitro. Moreover, recombinant LKB1 complex activates AMPK by phosphorylation of the alpha-subunit at the Thr-172 site as shown (i) by Western blotting using phospho-specific antibodies after LKB1-dependent phosphorylation, (ii) by LKB1-dependent incorporation of radioactive phosphate into the alpha-subunit of kinase dead AMPK heterotrimer, and (iii) by activity determination of AMPK. Functional mammalian LKB1 complex is constitutively active, and when enriched from bacteria should prove to be a valuable tool for studying its molecular function and regulation. PMID- 17873409 TI - Effect of the chitin binding domain deletion from Bacillus thuringiensis subsp. kurstaki chitinase Chi255 on its stability in Escherichia coli. AB - Bacillus thuringiensis subsp. kurstaki BUPM255 secretes a chitobiosidase Chi255 having an expected molecular weight of 70.665 kDa. When the corresponding gene, chi255, was expressed in E. coli, the active form, extracted from the periplasmic fraction of E. coli/pBADchi255, was of about 54 kDa, which suggested that Chi255 was excessively degraded by the action of E. coli proteases. Therefore, in vitro progressive C-terminal Chi255 deleted derivatives were constructed in order to study their stability and their activity in E. coli. Interestingly, when the chitin binding domain (CBD) was deleted from Chi255, an active form (Chi2555Delta5) of expected size of about 60 kDa was extracted from the E. coli periplasmic fraction, without the observation of any proteolytic degradation. Compared to Chi255, Chi255Delta5 exhibited a higher chitinase activity on colloidal chitin. Both of the enzymes exhibit activities at broad pH and temperature ranges with maximal enzyme activities at pH 5 and pH 6 and at temperatures 50 degrees C and 40 degrees C, respectively for Chi255 and Chi255Delta5. Thus, it was concluded that the C-terminal deletion of Chi255 CBD might be a nice tool for avoiding the excessive chitinase degradation, observed in the native chitinase, and for improving its activity. PMID- 17873410 TI - Classification of protein folds. AB - The diversity and complexity of bioinformatics tools currently available for protein sequence analysis can make it difficult to know where to begin when presented with a new sequence. In this article, we present a protocol outlining one approach to sequence analysis that should give as comprehensive a picture as possible as to the likely structure and function of a protein given the limits of available tools. We also provide worked examples showing how these tools can have an impact on the understanding of protein function prior to experimental studies. PMID- 17873412 TI - Stem cells engineering for cell-based therapy. AB - Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy. PMID- 17873413 TI - Advances in neural interfaces: report from the 2006 NIH Neural Interfaces Workshop. PMID- 17873414 TI - An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology. AB - Neural interface technology has made enormous strides in recent years but stimulating electrodes remain incapable of reliably targeting specific cell types (e.g. excitatory or inhibitory neurons) within neural tissue. This obstacle has major scientific and clinical implications. For example, there is intense debate among physicians, neuroengineers and neuroscientists regarding the relevant cell types recruited during deep brain stimulation (DBS); moreover, many debilitating side effects of DBS likely result from lack of cell-type specificity. We describe here a novel optical neural interface technology that will allow neuroengineers to optically address specific cell types in vivo with millisecond temporal precision. Channelrhodopsin-2 (ChR2), an algal light-activated ion channel we developed for use in mammals, can give rise to safe, light-driven stimulation of CNS neurons on a timescale of milliseconds. Because ChR2 is genetically targetable, specific populations of neurons even sparsely embedded within intact circuitry can be stimulated with high temporal precision. Here we report the first in vivo behavioral demonstration of a functional optical neural interface (ONI) in intact animals, involving integrated fiberoptic and optogenetic technology. We developed a solid-state laser diode system that can be pulsed with millisecond precision, outputs 20 mW of power at 473 nm, and is coupled to a lightweight, flexible multimode optical fiber, approximately 200 microm in diameter. To capitalize on the unique advantages of this system, we specifically targeted ChR2 to excitatory cells in vivo with the CaMKIIalpha promoter. Under these conditions, the intensity of light exiting the fiber ( approximately 380 mW mm(-2)) was sufficient to drive excitatory neurons in vivo and control motor cortex function with behavioral output in intact rodents. No exogenous chemical cofactor was needed at any point, a crucial finding for in vivo work in large mammals. Achieving modulation of behavior with optical control of neuronal subtypes may give rise to fundamental network-level insights complementary to what electrode methodologies have taught us, and the emerging optogenetic toolkit may find application across a broad range of neuroscience, neuroengineering and clinical questions. PMID- 17873415 TI - Blind source separation of peripheral nerve recordings. AB - Prosthetic devices can be controlled using signals recorded in parts of the body where sensation and/or voluntary movement have been retained. Although neural prosthetic applications have used single-channel recordings, multiple-channel recordings could provide a significant increase in useable control signals. Multiple control signals can be acquired from recordings of a single implant by using a multi-contact electrode placed over a multi-fasciculated peripheral nerve. These recordings can be separated to recover the individual fascicular signals. Blind source separation (BSS) algorithms have been developed to extract independent source signals from recordings of their mixtures. The hypothesis that BSS algorithms can recover individual fascicular signals from nerve cuff recordings at physiological signal-to-noise ratio (SNR approximately 3-10 dB) was investigated in this study using a finite-element model (FEM) of a beagle hypoglossal nerve with a flattening interface nerve electrode (FINE). Known statistical properties of fascicular signals were used to generate a set of four sources from which the neural signals recorded at the surface of the nerve with a multi-contact FINE were simulated. Independent component analysis (ICA) was then implemented for BSS of the simulated recordings. A novel post-ICA processing algorithm was developed to solve ICA's inherent permutation ambiguities. The similarity between the estimated and original fascicular signals was quantified by calculating their correlation coefficients. The mean values of the correlation coefficients calculated were higher than 0.95 (n = 50). The effects of the geometric layout of the FINE electrode and noise on the separation algorithm were also investigated. The results show that four distinct overlapping fascicular source signals can be simultaneously recovered from neural recordings obtained using a FINE with five or more contacts at SNR levels higher than 8 dB making them available for use as control signals. PMID- 17873416 TI - Limb-state feedback from ensembles of simultaneously recorded dorsal root ganglion neurons. AB - Functional electrical stimulation (FES) holds great potential for restoring motor functions after brain and spinal cord injury. Currently, most FES systems are under simple finite state control, using external sensors which tend to be bulky, uncomfortable and prone to failure. Sensory nerve signals offer an interesting alternative, with the possibility of continuous feedback control. To test feasibility, we recorded from ensembles of sensory neurons with microelectrode arrays implanted in the dorsal root ganglion (DRG) of walking cats. Limb position and velocity variables were estimated accurately (average R2 values >0.5) over a range of walking speeds (0.1-0.5 m s(-1)) using a linear combination of firing rates from 10 or more neurons. We tested the feasibility of sensory control of intraspinal FES by recording from DRG neurons during hindlimb movements evoked by intraspinal microstimulation of the lumbar spinal cord in an anesthetized cat. Although electrical stimulation generated artifacts, this problem was overcome by detecting and eliminating events that occurred synchronously across the array of microelectrodes. The sensory responses to limb movement could then be measured and decoded to generate an accurate estimate of the limb state. Multichannel afferent recordings may thus provide FES systems with the feedback needed for adaptive control and perturbation compensation, though long-term stability remains a challenge. PMID- 17873417 TI - New functional electrical stimulation approaches to standing and walking. AB - Spinal cord injury (SCI) is a devastating neurological trauma that is prevalent predominantly in young individuals. Several interventions in the areas of neuroregeneration, pharmacology and rehabilitation engineering/neuroscience are currently under investigation for restoring function after SCI. In this paper, we focus on the use of neuroprosthetic devices for restoring standing and ambulation as well as improving general health and wellness after SCI. Four neuroprosthetic approaches are discussed along with their demonstrated advantages and their future needs for improved clinical applicability. We first introduce surface functional electrical stimulation (FES) devices for restoring ambulation and highlight the importance of these devices for facilitating exercise activities and systemic physiological activation. Implanted muscle-based FES devices for restoring standing and walking that are currently undergoing clinical trials are then presented. The use of implanted peripheral nerve intraneural arrays of multi site microelectrodes for providing fine and graded control of force during sit-to stand maneuvers is subsequently demonstrated. Finally, intraspinal microstimulation (ISMS) of the lumbosacral spinal cord for restoring standing and walking is introduced and its results to date are presented. We conclude with a general discussion of the common needs of the neuroprosthetic devices presented in this paper and the improvements that may be incorporated in the future to advance their clinical utility and user satisfaction. PMID- 17873418 TI - Detection of spectral instability in EEG recordings during the preictal period. AB - The study of EEG recordings during the interval prior to an epileptic seizure onset--the preictal period--is likely to detect changes in the ongoing brain activity consistent with seizure anticipation. A novel index of spectral instability (ISpI) based on multiple abrupt changes of EEG spectral features is presented here. Based on the analysis of control records, robust M-estimates are used to calculate the threshold and avoid false warnings. The results obtained with a small data set (three patients, ten preictal records per patient) have shown that the ISpI index provided a warning flag that anticipated the seizure onset by 13.1 (SD = 4.0) min on average. PMID- 17873419 TI - Functional consequences of model complexity in rhythmic systems: I. Systematic reduction of a bursting neuron model. AB - Neural models are increasingly being used as design components of physical systems. In order to most effectively utilize neuronal models in these novel contexts, we need to develop design rules for neuronal systems that relate how model design affects overall system performance. In this paper and a companion article, we investigate how the complexity of a neural model affects the performance of a two-cell oscillator built from the model. In this paper, we create a series of related neuron models with different mathematical complexity. Starting with a complex mechanistic model of a bursting neuron, we use a variety of techniques to create a series of simplified neuron models. These three reduced models produce bursting activity that is qualitatively very similar to the original model. In the following companion article, we investigate the functional performance of oscillators built from these models. PMID- 17873420 TI - Functional consequences of model complexity in rhythmic systems: II. Systems performance of model and hybrid oscillators. AB - Neural models are increasingly being used as design components of physical systems. In order to best use models in these novel contexts, we must develop design rules that describe how decisions in model construction relate to the functional performance of the resulting system. In the accompanying paper, we described a series of related neuron models of varying complexity. Here, we use these models to build several half-center oscillators, and investigate how model complexity influences the robustness and flexibility of these oscillators. Our results indicate that model complexity has a significant effect on the robustness and flexibility of systems that incorporate neural models. PMID- 17873421 TI - Effects of holes on EEG forward solutions using a realistic geometry head model. AB - Holes in the skull and the scalp are associated with intracranial monitoring procedures. The purpose of the present study is to evaluate the effects of holes on extracranial electroencephalogram (EEG) and intracranial electrocorticogram (ECoG) recordings. The finite difference method (FDM) was used to model the head volume conductor with a hole of varying size. A current dipole was used to simulate the brain electrical activity with varying locations within the brain. The effects of the holes were assessed by comparing the forward potential distributions with and without a hole. The present computer simulation results indicate that the effect of a hole on the scalp EEG and ECoG recordings strongly depends on the dipole location and orientation. For a superficial radial dipole located under a hole of radius ranging from 5 mm to 40 mm, the relative error (RE) varies from 0.99% to 93.07% for the EEG and from 0.025% to 16.72% for the ECoG. The correlation coefficient (CC) varies from 99.99% to 21.1% and from 100% to 99.75% for the EEG and EcoG, respectively. For radial dipoles, the strongest effect on the EEG and ECoG occurs when the dipole is located below the center of the hole, while for tangential dipoles, the strongest effect occurs when the dipole is located below the border of the hole. The effect of a hole on the EEG is much larger than upon the ECoG. PMID- 17873422 TI - Quasi-trapezoidal pulses to selectively block the activation of intrinsic laryngeal muscles during vagal nerve stimulation. AB - The stimulation of the vagus nerve has been used as an anti-epileptic treatment for over a decade, and its use for depression and chronic heart failure is currently under investigation. Co-activation of the intrinsic laryngeal muscles may limit the clinical use of vagal stimulation, especially in the case of prolonged activation. To prevent this, the use of a selective stimulation paradigm has been tested in seven acute pig experiments. Quasi-trapezoidal pulses successfully blocked the population of the largest and fastest vagal myelinated fibers being responsible for the co-activation. The first response in the vagus compound action potential was reduced by 75 +/- 22% (mean +/- SD) and the co activated muscle action potential by 67 +/- 25%. The vagal bradycardic effects remained unchanged during the selective block, confirming the leading role of thin nerve fibers for the vagal control of the heart. Quasi-trapezoidal pulses may be an alternative to rectangular pulses in clinical vagal stimulation when the co-activation of laryngeal muscles must be avoided. PMID- 17873423 TI - A microscale photovoltaic neurostimulator for fiber optic delivery of functional electrical stimulation. AB - Recent advances in functional electrical stimulation (FES) show significant promise for restoring voluntary movement in patients with paralysis or other severe motor impairments. Current approaches for implantable FES systems involve multisite stimulation, posing research issues related to their physical size, power and signal delivery, surgical and safety challenges. To explore a different means for delivering the stimulus to a distant muscle nerve site, we have elicited in vitro FES response using a high efficiency microcrystal photovoltaic device as a neurostimulator, integrated with a biocompatible glass optical fiber which forms a lossless, interference-free lightwave conduit for signal and energy transport. As a proof of concept demonstration, a sciatic nerve of a frog is stimulated by the microcrystal device connected to a multimode optical fiber (core diameter of 62.5 microm), which converts optical activation pulses ( approximately 100 micros) from an infrared semiconductor laser source (at 852 nm wavelength) into an FES signal. PMID- 17873424 TI - Brain-computer interface using a simplified functional near-infrared spectroscopy system. AB - A brain-computer interface (BCI) is a device that allows a user to communicate with external devices through thought processes alone. A novel signal acquisition tool for BCIs is near-infrared spectroscopy (NIRS), an optical technique to measure localized cortical brain activity. The benefits of using this non invasive modality are safety, portability and accessibility. A number of commercial multi-channel NIRS system are available; however we have developed a straightforward custom-built system to investigate the functionality of a fNIRS BCI system. This work describes the construction of the device, the principles of operation and the implementation of a fNIRS-BCI application, 'Mindswitch' that harnesses motor imagery for control. Analysis is performed online and feedback of performance is presented to the user. Mindswitch presents a basic 'on/off' switching option to the user, where selection of either state takes 1 min. Initial results show that fNIRS can support simple BCI functionality and shows much potential. Although performance may be currently inferior to many EEG systems, there is much scope for development particularly with more sophisticated signal processing and classification techniques. We hope that by presenting fNIRS as an accessible and affordable option, a new avenue of exploration will open within the BCI research community and stimulate further research in fNIRS-BCIs. PMID- 17873425 TI - Non-rectangular waveforms for neural stimulation with practical electrodes. AB - Historically the rectangular pulse waveform has been the choice for neural stimulation. The strength-duration curve is thus defined for rectangular pulses. Not much attention has been paid to alternative waveforms to determine if the pulse shape has an effect on the strength-duration relation. Similarly the charge injection capacity of neural electrodes has also been measured with rectangular pulses. In this study we questioned if non-rectangular waveforms can generate a stronger stimulation effect, when applied through practical electrodes, by minimizing the neural activation threshold and maximizing the charge injection capacity of the electrode. First, the activation threshold parameters were studied with seven different pulse shapes using computer simulations of a local membrane model. These waveforms were rectangular, linear increase and decrease, exponential increase and decrease, Gaussian, and sinusoidal. The chronaxie time was found to be longer with all the non-rectangular pulses and some provided more energy efficient stimulation than the rectangular waveform. Second, the charge injection capacity of titanium nitride microelectrodes was measured experimentally for the same waveforms. Linearly decreasing ramp provided the best charge injection for all pulse widths tested from 0.02 to 0.5 ms. Finally, the most efficient waveform that maximized the charge injection capacity of the electrode while providing the lowest threshold charge for neural activation was searched. Linear and exponential decrease, and Gaussian waveforms were found to be the most efficient pulse shapes. PMID- 17873427 TI - Transductive SVM for reducing the training effort in BCI. AB - A brain-computer interface (BCI) provides a communication channel that translates human intention reflected by a brain signal such as electroencephalogram (EEG) into a control signal for an output device. In this work, the main concern is to reduce the training effort for BCI, which is often tedious and time consuming. Here we introduce a transductive support vector machines (TSVM) algorithm for the classification of EEG signals associated with mental tasks. TSVM possess the property of using both labeled and unlabeled data for reducing the calibration time in BCI and achieving good performance in classification accuracy. The advantages of the proposed method over the traditional supervised support vector machines (SVM) method are confirmed by about 2%-9% higher classification accuracies on a set of EEG recordings of three subjects from three-tasks-based mental imagery experiments. PMID- 17873426 TI - Asymmetric interjoint feedback contributes to postural control of redundant multi link systems. AB - Maintaining the postural configuration of a limb such as an arm or leg is a fundamental neural control task that involves the coordination of multiple linked body segments. Biological systems are known to use a complex network of inter- and intra-joint feedback mechanisms arising from muscles, spinal reflexes and higher neuronal structures to stabilize the limbs. While previous work has shown that a small amount of asymmetric heterogenic feedback contributes to the behavior of these systems, a satisfactory functional explanation for this non conservative feedback structure has not been put forth. We hypothesized that an asymmetric multi-joint control strategy would confer both an energetic and stability advantage in maintaining endpoint position of a kinematically redundant system. We tested this hypothesis by using optimal control models incorporating symmetric versus asymmetric feedback with the goal of maintaining the endpoint location of a kinematically redundant, planar limb. Asymmetric feedback improved endpoint control performance of the limb by 16%, reduced energetic cost by 21% and increased interjoint coordination by 40% compared to the symmetric feedback system. The overall effect of the asymmetry was that proximal joint motion resulted in greater torque generation at distal joints than vice versa. The asymmetric organization is consistent with heterogenic stretch reflex gains measured experimentally. We conclude that asymmetric feedback has a functionally relevant role in coordinating redundant degrees of freedom to maintain the position of the hand or foot. PMID- 17873428 TI - Studies of host-graft interactions in vitro. AB - Progenitor and stem cell transplantation represent therapeutic strategies for retinal disorders that are accompanied by photoreceptor degeneration. The transplanted cells may either replace degenerating photoreceptors or secrete beneficial factors that halt the processes of photoreceptor degeneration. The present study analyzes whether rat retinal progenitor cells differentiated into photoreceptor phenotypic cells in neurospheres have a potential to interact with rat retinal explants. Immunocytochemistry for rhodopsin and synaptophysin indicated photoreceptor cell-like differentiation in neurospheres that were stimulated by basic fibroblast growth factor and epidermal growth factor. Differentiation into neural phenotypes including photoreceptor cells was effectively blocked by an addition of leukemia inhibitory factor. Grafting of neurospheres onto retinal explants demonstrated a consistent penetration of glial cell processes into the explanted tissue. On the other hand, the incorporation of donor cells into explants was very low. A general finding was that neurospheres grafting was associated with local decrease in Muller cell activation in the explants. Further characterization of these effect(s) could provide further insight into progenitor cell-based therapies of retinal degenerative disorders. PMID- 17873429 TI - Decoding two-dimensional movement trajectories using electrocorticographic signals in humans. AB - Signals from the brain could provide a non-muscular communication and control system, a brain-computer interface (BCI), for people who are severely paralyzed. A common BCI research strategy begins by decoding kinematic parameters from brain signals recorded during actual arm movement. It has been assumed that these parameters can be derived accurately only from signals recorded by intracortical microelectrodes, but the long-term stability of such electrodes is uncertain. The present study disproves this widespread assumption by showing in humans that kinematic parameters can also be decoded from signals recorded by subdural electrodes on the cortical surface (ECoG) with an accuracy comparable to that achieved in monkey studies using intracortical microelectrodes. A new ECoG feature labeled the local motor potential (LMP) provided the most information about movement. Furthermore, features displayed cosine tuning that has previously been described only for signals recorded within the brain. These results suggest that ECoG could be a more stable and less invasive alternative to intracortical electrodes for BCI systems, and could also prove useful in studies of motor function. PMID- 17873430 TI - An analysis of glutamate spillover on the N-methyl-D-aspartate receptors at the cerebellar glomerulus. AB - Glutamate spillover is thought to play a significant role in increasing neural transmission at the mossy fiber/granule cell cerebellar glomerulus. Glutamate spillover has been shown to activate AMPA receptors at the glomerulus, and here we complete the characterization of spillover at the glomerulus by investigating the role of glutamate spillover in N-methyl-D-aspartate receptor (NMDA-R) activation. We present a quantitative model of glutamate spillover combining recent models of glutamate diffusion and NMDA-R binding to determine the open probabilities of NMDA-Rs over time at a neighbor synapse. Simulation results from a baseline set of physiologically realistic parameters show that glutamate spillover onto a single neighbor synapse, created by glutamate that diffuses from a point source into a restricted fractional 2D-3D space and the glutamate concentration created by neighboring glutamate release sites, is sufficient to elicit an NMDA-R peak open probability of 0.23, approximately 79% of that obtained by a direct release (peak open probability of 0.29). Thus, it would appear that glutamate spillover at the glomerulus at NMDA receptors is even more substantial than that seen at AMPA receptors. PMID- 17873431 TI - Transmembrane potential induced in a spherical cell model under low-frequency magnetic stimulation. AB - Time-varying magnetic fields can induce electric fields in the neuronal tissue, a phenomenon that has been recently explored in clinical applications such as peripheral nerve stimulation and transcranial magnetic stimulation. Although the transmembrane potential induced during direct electric stimulation has already been the subject of a number of theoretical studies, an analytical solution for the magnetically induced transmembrane potential change is still unavailable. In addition, although several studies have analyzed the impact of stimulation parameters, including stimulation intensity and frequency, as well as coil design and position, on the amount of tissue polarization, the effects of tissue non homogeneity on cell polarization have not been fully elucidated. In this study, we have derived an analytical expression for the transmembrane potential induced by a low-frequency magnetic field in a spherical neuronal structure. This model is representative of a spherical cell body or any neuronal structure of a similar shape. The model cell is located in an extracellular medium and possesses a low conductive membrane and an internal cytoplasm. These three regions represent the basic tissue non-homogeneity of a neuron at a microscopic level. The sensitivity of the induced transmembrane potential to the coil position and to the geometrical and electrical parameters of the model structure was studied in a broad physiologically relevant range. Our results demonstrate that the structure is regionally polarized, with the pattern of polarization depending on the relative positioning between the model cell and the stimulation coil. In addition, both the geometrical and electrical parameters of the structure affect the amount of polarization. These results may be generalized to other neuronal tissues that possess similar non-homogenous properties, but different shapes, such as an axon. Our results support the idea that aside from coil design and position, tissue non-homogeneity could play an important role in determining the effects of magnetic stimulation. PMID- 17873433 TI - A single-chip signal processing and telemetry engine for an implantable 96 channel neural data acquisition system. AB - A fully implantable neural data acquisition system is a key component of a clinically viable cortical brain-machine interface. We present the design and implementation of a single-chip device that serves the processing needs of such a system. Our device processes 96 channels of multi-unit neural data and performs all digital processing necessary for bidirectional wireless communication. The implementation utilizes a single programmable logic device that is responsible for performing data reduction on the 96 channels of neural data, providing a bidirectional telemetry interface to a transceiver and performing command interpretation and system supervision. The device takes as input neural data sampled at 31.25 kHz and outputs a line-encoded serial bitstream containing the information to be transmitted by the transceiver. Data can be output in one of the following four modes: (1) streaming uncompressed data from a single channel, (2) extracted spike waveforms from any subset of the 96 channels, (3) 1 ms bincounts for each channel or (4) streaming data along with extracted spikes from a single channel. The device can output up to 2000 extracted spikes per second with latencies suitable for a brain-machine interface application. This device provides all of the digital processing components required by a fully implantable system. PMID- 17873432 TI - Region-specific network plasticity in simulated and living cortical networks: comparison of the center of activity trajectory (CAT) with other statistics. AB - Electrically interfaced cortical networks cultured in vitro can be used as a model for studying the network mechanisms of learning and memory. Lasting changes in functional connectivity have been difficult to detect with extracellular multi electrode arrays using standard firing rate statistics. We used both simulated and living networks to compare the ability of various statistics to quantify functional plasticity at the network level. Using a simulated integrate-and-fire neural network, we compared five established statistical methods to one of our own design, called center of activity trajectory (CAT). CAT, which depicts dynamics of the location-weighted average of spatiotemporal patterns of action potentials across the physical space of the neuronal circuitry, was the most sensitive statistic for detecting tetanus-induced plasticity in both simulated and living networks. By reducing the dimensionality of multi-unit data while still including spatial information, CAT allows efficient real-time computation of spatiotemporal activity patterns. Thus, CAT will be useful for studies in vivo or in vitro in which the locations of recording sites on multi-electrode probes are important. PMID- 17873434 TI - An analytical comparison of the information in sorted and non-sorted cosine-tuned spike activity. AB - Spike sorting is a technologically expensive component of the signal processing chain required to interpret population spike activity acquired in a neuromotor prosthesis. No systematic analysis of the value of spike sorting has been carried out, and little is known about the effects of spike sorting error on the ability of a brain-machine interface (BMI) to decode intended motor commands. We developed a theoretical framework to examine the effects of spike processing on the information available to a BMI decoder. We computed the mutual information in neural activity in a simplified model of directional cosine tuning to compare the effects of pooling activity from up to four neurons to the effects of sorting with varying amounts of spike error. The results showed that information in a small population of cosine-tuned neurons is maximized when the responses are sorted and there is diverse tuning of units, but information was affected little when pooling units with similar preferred directions. Spike error had adverse effects on information, such that non-sorted population activity had 79-92% of the information in its sorted counterpart for reasonable amounts of detection and sorting error and for units with moderate differences in preferred direction. This quantification of information loss associated with pooling units and with spike detection and sorting error will help to guide the engineering decisions in designing a BMI spike processing system. PMID- 17873436 TI - Structure and oxygen mobility in mayenite (Ca12Al14O33): a high-temperature neutron powder diffraction study. AB - The structure of mayenite, Ca(12)Al(14)O(33), was investigated by neutron powder diffraction up to 1323 K. It has been described previously as a calcium-aluminate framework, in which 32 of the 33 oxygen anions are tightly bound, containing large cages, 1/6 of them being filled randomly by the remaining 'free' oxygen. At ambient temperature excess oxygen was found, corresponding to the composition Ca(12)Al(14)O(33.5) which was attributed to the presence of hydroxide, peroxide and superoxide radicals in the cages. Above 973 K these are lost under vacuum conditions and the composition becomes stoichiometric. From the refined structural parameters it is concluded that the structure is more adequately described as a relatively stable aluminate framework consisting of eightfold rings of AlO(4) tetrahedra with disordered Ca and 'free' O distributed within. At high temperatures the density of the 'free' oxygen is extremely spread out, with the expansion being related to the high ionic conductivity of this material. Since no continuous density distribution between adjacent cages was found and the 'free' O forms bonds with part of the Ca, the diffusion proceeds via a jump-like process involving exchange of the 'free' oxygen with framework oxygen. The results confirm the recent theoretical predictions of Sushko et al. PMID- 17873435 TI - Free-paced high-performance brain-computer interfaces. AB - Neural prostheses aim to improve the quality of life of severely disabled patients by translating neural activity into control signals for guiding prosthetic devices or computer cursors. We recently demonstrated that plan activity from premotor cortex, which specifies the endpoint of the upcoming arm movement, can be used to swiftly and accurately guide computer cursors to the desired target locations. However, these systems currently require additional, non-neural information to specify when plan activity is present. We report here the design and performance of state estimator algorithms for automatically detecting the presence of plan activity using neural activity alone. Prosthesis performance was nearly as good when state estimation was used as when perfect plan timing information was provided separately ( approximately 5 percentage points lower, when using 200 ms of plan activity). These results strongly suggest that a completely neurally-driven high-performance brain-computer interface is possible. PMID- 17873437 TI - Inversion of 4f-states in CeB6 thermally excited at 430 K. AB - The 4f states of Ce in a typical Kondo crystal, CeB(6), are split into an excited state Gamma(7) and the ground state Gamma(8), with an excitation energy at 560 K. The electron-density distribution of the thermally excited state was measured at 430 K using a four-circle diffractometer equipped with a small furnace. In contrast to the previous results at lower temperature, electrons are transferred from B(6) to Ce at 430 K. X-ray atomic-orbital analysis revealed that the 5d Gamma(8) orbitals (the energy level of which is similar to that of the B-2p orbitals) are fully occupied and the 4f-Gamma(7) orbitals are more populated than the 4f-Gamma(8) orbitals. Fully occupied 5d-Gamma(8) makes the 4f-Gamma(8) states unstable and the energy levels of 4f-Gamma(7) and 4f-Gamma(8) are inverted. PMID- 17873438 TI - Revision of pyrrhotite structures within a common superspace model. AB - The structure of pyrrhotite (Fe(1 - x)S with 0.05 < or = x < or = 0.125) has been reinvestigated in the framework of the superspace formalism. A common model with a centrosymmetric superspace group is proposed for the whole family. The atomic domains in the internal space representing the Fe atoms are parametrized as crenel functions that fulfil the closeness condition. The proposed model explains the x-dependent space groups observed and the basic features of the structures reported up to now. Our model yields for any x value a well defined ordered distribution of Fe vacancies in contrast to some of the structural models proposed in the literature. A new (3 + 1)-dimensional refinement of Fe(0.91)S using the deposited dataset [Yamamoto & Nakazawa (1982). Acta Cryst. A38, 79-86] has been performed as a benchmark of the model. The consistency of the proposed superspace symmetry and its validity for other compositions has been further checked by means of ab initio calculations of both atomic forces and equilibrium atomic positions in non-relaxed and relaxed structures, respectively. PMID- 17873439 TI - Hexagonal ferrites: a unified model of the (TS)nT series in superspace. AB - Hexagonal ferrites represent an extensive family of mixed-layer magnetic materials with periods up to 1500 A along the stacking direction, probably constituting the largest unit cells in the inorganic realm. The (TS)(n)T subfamily includes P3m1 and R3m structures that can be derived from Y ferrite Ba(2)M(2)Fe(12)O(22) (M = Zn, Fe, Co, Mg, Mn) by introducing stacking faults. A unified (3 + 1)-dimensional superspace model is proposed for all members of the (TS)(n)T family. The model belongs to the superspace group X3m1(00gamma) with X = {(1/3, 2/3, 0, 1/3), (2/3, 1/3, 0, 2/3)}, has a unit cell of the basic structure with a = 5.88, c = 4.84 A and modulation vector q = 4n+3/9n+6 c*, where n is rational for periodic structures and irrational for the aperiodic ones. The model was tested on calculated data of one of the principal members of the (TS)(n)T family, the Y ferrite (n = infinity). The fit obtained with the superspace model was excellent. The model allowed a reduction of refinable parameters by 19% with respect to the ordinary refinement without a significant increase of the refinement R values. PMID- 17873440 TI - X-ray powder diffraction structural characterization of Pb1-xBaxZr0.65Ti0.35O3 ceramic. AB - The structure of Pb(1-x)Ba(x)Zr(0.65)Ti(0.35)O(3) (PBZT) ceramic materials with 0.00 < or = x < or = 0.40 was studied using synchrotron X-ray powder diffraction data. According to the Rietveld refinements, the structure of PBZT ceramics with x = 0.00, 0.10 and 0.20 at room temperature was rhombohedral R3c. A phase transition from rhombohedral to cubic was observed at 543 and 463 K for x = 0.10 and 0.20, respectively. The refinement for the compositions x = 0.30 and x = 0.40 showed a cubic structure from 10 to 450 K, in good agreement with the dielectric properties of these samples. PMID- 17873441 TI - Structure of RbFeO2, refined from a reticular pseudomerohedrally twinned crystal with six domains. AB - RbFeO(2), rubidium oxoferrate, crystallizes as an orthorhombic structure. The crystals under investigation were composed of six individuals representing reticular pseudomerohedral twins with a pseudocubic twin lattice of index 4 because of the approximate equations a(8)(1/2) = b(2)(1/2) = c. The compound is isostructural with KFeO(2) (KGaO(2) type of structure) and is composed of [FeO(4/2)](-) corner-sharing tetrahedra, forming a three-dimensional cristobalite like network, with Rb(+) ions occupying its interstices. PMID- 17873442 TI - Structure determination of structurally complex Ag36Li64 gamma-brass. AB - The crystal structure of the Ag(36)Li(64) gamma-brass was determined by analyzing the powder diffraction pattern taken using a synchrotron radiation beam with wavelength 0.50226 A. It turned out that the compound contained 52 atoms in its unit cell with the space group I43m and that the Li atom enters exclusively into inner tetrahedral (IT) and cubo-octahedral (CO) sites, whereas the Ag atom enters into those on outer tetrahedral (OT) and octahedral (OH) sites in the 26-atom cluster. Small amounts of Li also exist in OT and OH sites, resulting in chemical disorder. We discovered that the volumes of the IT and CO polyhedra shrink, while those of the OT and OH polyhedra expand relative to those of the corresponding polyhedra in the original b.c.c. (body-centered cubic) structure. This feature is universal and is found in other gamma-brasses such as Cu(5)Zn(8) and Al(8)V(5), for which the structure data are available. Among these gamma-brasses, we revealed the unique bond-length distribution for pairs connecting the atom on OH sites and that on CO sites, depending on the degree of d-p orbital hybridization between the transition metal elements such as Ag, Cu and V on OH sites, and the non-transition metal elements such as Li, Zn and Al on CO sites. It is suggested that this may hold a clue to resolving why some gamma-brasses such as the present Ag-Li and Cu-Zn possess a finite solid solution, but others such as Al(8)V(5) and Mn(3)In exist as line compounds. PMID- 17873443 TI - Synthesis, characterization and phase transitions in the inorganic-organic layered perovskite-type hybrids [(CnH2n+1NH3)2PbI4], n = 4, 5 and 6. AB - Three inorganic-organic layered perovskite-type hybrids of the general formula [(C(n)H(2n+1)NH(3))(2)PbI(4)], n = 4, 5 and 6, display a number of reversible first-order phase transitions in the temperature range from 256 to 393 K. [(C(4)H(9)NH(3))(2)PbI(4)] has a single phase transition, [(C(5)H(11)NH(3))(2)PbI(4)] has two phase transitions and [(C(6)H(13)NH(3))(2)PbI(4)] has three phase transitions. In all three cases, the lowest-temperature phase transition is thermochromic and the crystals change colour from yellow in their lowest-temperature phase to orange in their higher temperature phase for [(C(4)H(9)NH(3))(2)PbI(4)] and [(C(6)H(13)NH(3))(2)PbI(4)], and from orange to red for [(C(5)H(11)NH(3))(2)PbI(4)]. The structural details associated with this phase transition have been investigated via single-crystal X ray diffraction, SC-XRD, for all three compounds. PMID- 17873444 TI - Asymmetric hydrogen bonds in a centrosymmetric environment. III. Quantum mechanical calculations of the potential-energy surfaces for the very short hydrogen bonds in potassium hydrogen dichloromaleate. AB - In the crystal structure of potassium hydrogen dichloromaleate there are two short hydrogen bonds of 2.44 A. The 'heavy-atom' structure is centrosymmetric (space group P1) with centers of symmetry in the middle of the O-O bonds, suggesting centered hydrogen bonds. However, earlier unconventional types of refinements of the extensive neutron data taken at 30, 90, 135, 170 and 295 K demonstrated that the H atoms are actually non-centered in the hydrogen bonds, although the environment is centrosymmetric. Traditionally it has been assumed that the hydrogen distribution adopts the same symmetry as the environment. Reviewing these unusual results it was considered of great interest to verify that the non-centered locations of the H atoms are reasonable from an energy point of view. Quantum mechanical calculations have now been carried out for the potential-energy surfaces (PES) for both the centered and non-centered locations of the H atoms. In all cases the non-centered positions are closer to the energy minima in the PES than the centered positions, and this result confirms that the structure is best described with non-centered H atoms. There is virtually perfect agreement between the quantum-mechanically derived reaction coordinates (QMRC) and the bond-order reaction coordinates (BORC) derived using Pauling's bond-order concept together with the principle of conservation of bond order. [Part I: Olovsson et al. (2001). Acta Cryst. B57, 311-316; Part II: Olovsson et al. (2002). Acta Cryst. B58, 627-631.]. PMID- 17873445 TI - Experimental charge density of L-alanyl-L-prolyl-L-alanine hydrate: classical multipole and invariom approach, analysis of intra- and intermolecular topological properties. AB - A high-resolution dataset of the tripeptide L-alanyl-L-prolyl-L-alanine hydrate was measured at 100 K using synchrotron radiation and CCD area detection. Electron densities were obtained from a full multipole refinement of the X-ray experimental data, from an invariom transfer and from a theoretical calculation. Topological and atomic properties were derived via an AIM analysis [Atoms in Molecules; see Bader (1990). Atoms in Molecules: A Quantum Theory, No. 22 in International Series of Monographs on Chemistry, 1st ed. Oxford: Clarendon Press] of these densities and compared with each other, as well as with results from the literature of other oligopeptides and amino acids. By application of the invariom formalism to a dataset of limited resolution, its performance was compared with a conventional spherical refinement, highlighting the possibility of aspherically modelling routine structure-determination experiments. The hydrogen-bonding scheme was subject to a detailed analysis according to the criteria of Koch & Popelier [(1995), J. Phys. Chem. 99, 9747-9754] as well as to the characterization of Espinosa et al. [(1998), Chem. Phys. Lett. 285, 170-173; (1999), Acta Cryst. B55, 563-572; (2002), J. Chem. Phys. 117, 5529-5542] using the results from the refined and invariom multipole densities as well as the spherical-density model, which are critically compared. PMID- 17873446 TI - Knowledge-based model of hydrogen-bonding propensity in organic crystals. AB - A new method is presented to predict which donors and acceptors form hydrogen bonds in a crystal structure, based on the statistical analysis of hydrogen bonds in the Cambridge Structural Database (CSD). The method is named the logit hydrogen-bonding propensity (LHP) model. The approach has a potential application in identifying both likely and unusual hydrogen bonding, which can help to rationalize stable and metastable crystalline forms, of relevance to drug development in the pharmaceutical industry. Whilst polymorph prediction techniques are widely used, the LHP model is knowledge-based and is not restricted by the computational issues of polymorph prediction, and as such may form a valuable precursor to polymorph screening. Model construction applies logistic regression, using training data obtained with a new survey method based on the CSD system. The survey categorizes the hydrogen bonds and extracts model parameter values using descriptive structural and chemical properties from three dimensional organic crystal structures. LHP predictions from a fitted model are made using two-dimensional observables alone. In the initial cases analysed, the model is highly accurate, achieving approximately 90% correct classification of both observed hydrogen bonds and non-interacting donor-acceptor pairs. Extensive statistical validation shows the LHP model to be robust across a range of small molecule organic crystal structures. PMID- 17873447 TI - Structures of tetrabromothiophene and tetrabromoselenophene: the influence of the heteroatom on the heterophene packing. AB - The crystal structures of C(4)Br(4)S and C(4)Br(4)Se have been determined from X ray powder diffraction data, using direct-space search techniques. In the case of C(4)Br(4)S two crystalline phases occur, a stable orthorhombic and a metastable monoclinic phase. For the orthorhombic phase two different structural models were found that fit the experimental data equally well. The diversity in crystal structure models and packings of C(4)Br(4)S is explained. PMID- 17873448 TI - Three-dimensional hydrogen-bonded frameworks in organic crystals: a topological study. AB - 1551 homomolecular single hydrogen-bonded frameworks in organic crystals have been classified into 148 topological types of three-periodic nets. Different representations of hydrogen-bonded frameworks as nets of molecular centroids, edge or ring nets are discussed. To study the influence of hydrogen bonds on the topology of molecular packings, 42,270 molecular crystals without hydrogen bonds have been considered. The topologies of molecular packings are found to be independent of hydrogen bonding. Analysis of 231 homomolecular frameworks composed of crystallographically different molecules shows that molecules not related by symmetry tend to form the same hydrogen-bond pattern. The relations between net topological types, space-group symmetry of crystals, site symmetry and point-group symmetry of molecules are discussed. As a result, a set of rules for the crystal design of molecular frameworks is proposed. PMID- 17873450 TI - Erwin H. Ackerknecht, social medicine, and the history of medicine. AB - Erwin H. Ackerknecht was an influential member of that small group of largely emigre historians of medicine who professionalized their field in the United States. Ackerknecht was influenced by both contemporary social science and an implicitly political vision of social medicine. It was a vision reinforced by his work in social anthropology in Paris in the 1930s, and it is a tradition that has its own intellectual pedigree, one that can be traced back to the era of Rudolf Virchow. It was no accident that Ackerknecht wrote on the social and ecological dimensions of disease, and that he was a vigorous advocate of a powerfully felt but, in retrospect, inconsistent relativism. His emphases on everyday medical practice and on siting ideas in their social and institutional context seem prescient, a forerunner of contemporary trends in social and cultural history. PMID- 17873451 TI - "The English disease" or "Asian rickets"? Medical responses to postcolonial immigration. AB - Do the former colonizing powers, like their former colonies, have "postcolonial medicine," and if so, where does it take place, who practices it, and upon whom? How has British medicine in particular responded to the huge cultural shifts represented by the rise of the New Commonwealth and associated postcolonial immigration? I address these questions through a case study of the medical and political responses to vitamin D deficiency among Britain's South Asian communities since the 1960s. My research suggests that in these contexts, diet frequently became a proxy or shorthand for culture (and religion, and race), while disease justified pressure to assimilate. PMID- 17873452 TI - Teamwork, clinical research, and the development of scientific medicines in interwar Britain: the "Glasgow School" revisited. AB - This article argues that historians of medicine have, until very recently, misinterpreted the relationship of "science" and "the clinic" in the early twentieth century. It follows recent historiographic developments in focusing on the relationship in practice as exemplified by the development of a specific variety of collaborative clinical research using laboratory methods, ca. 1919-37, in a major British medical school. It suggests that it is such working hybrids that should be studied in order to understand fully the development of scientific medicines in the United Kingdom in this period. In Glasgow, it was the local medical culture's characteristic local subservience to clinical priorities that facilitated, in a particular kind of academic unit, a certain type of hierarchical teamwork between clinicians and laboratory workers; the paper reveals how and why this teamwork became, over time, more of an equal partnership. PMID- 17873453 TI - Healthcare reconsidered: forging community wellness among African Americans in the south. AB - This article details the history of Slossfield Hospital, an African American hospital and community center founded in Birmingham, Alabama, in 1937. During its New Deal-era existence it provided African American physicians institutional support for their medical practices. Additionally, as a community center, it addressed the socioeconomics of good health. This paper uses Slossfield as a case study to explore how some African Americans included the socioeconomic in their definition of public health during the New Deal, as well as to understand how these ideas were subsumed by more mainstream ideas about public health promulgated by black and white physicians and the local and federal governments. PMID- 17873458 TI - Controversies in the adjuvant treatment of pancreatic adenocarcinoma. AB - There is no universally accepted standard approach to treat patients with pancreatic cancer in the adjuvant setting. This controversy derives from several studies, each fraught with its own limitations. Standards of care also vary depending on which side of the Atlantic you are on: chemo-radiotherapy followed by chemotherapy is considered the optimal therapy in North America (GITSG, RTOG) while chemotherapy alone is the current standard in Europe (ESPAC-1, CONKO). Whether gemcitabine is superior to 5-FU remains to be learnt from the ESPAC-3 study currently on-going in Europe. A number of important questions have yet to be fully addressed: What is the absolute value of radiotherapy in this setting? How should radiotherapy be delivered, if at all? What should be the time to deliver of either or both therapeutic modalities in the adjuvant setting? Are there any patients who can benefit from the combined modality? What is the most appropriate chemotherapeutic agent(s) to administer in the adjuvant setting? Is there any role of integrating the novel/targeted agents, albeit the negative studies in the metastatic setting? What are the new developments (such as vaccines, pancreas cancer stem cells, etc.) in this area? The author summarizes the evolution of adjuvant therapy for resected pancreatic cancer and highlights the controversies that originate from several studies, each fraught with its own limitations. PMID- 17873460 TI - Histopathological sequential changes in sodium taurocholate-induced acute pancreatitis. AB - CONTEXT: Experimental models of acute pancreatitis have been developed in order to understand its pathophysiology and extrapancreatic manifestations. OBJECTIVE: The objective of our study was to study sequential changes in the pancreas and distant organs in sodium taurocholate-induced acute pancreatitis in a rat model. ANIMALS: Sixteen male Wistar rats weighing 250-300 g. DESIGN: The rats were distributed into two groups: induced acute pancreatitis (study group: 8 rats) and a control group (8 rats). Within each group, the animals were divided into subgroups: those who were sacrificed early (24 h and 72 h; two each) and those who were sacrificed late (120 h and 240 h; two each). INTERVENTION: Acute pancreatitis was induced in the rats by multiple intraparenchymal injections of 10% sodium taurocholate solution. In the controls, the same amount of normal saline was injected into the pancreatic parenchyma. MAIN OUTCOME MEASURES: Pathological examination of the pancreas, lungs, kidneys, intestine and liver was done. RESULTS: In this model of taurocholate-induced acute pancreatitis, the early changes observed in the pancreas were focal hemorrhages, parenchymal necrosis and neutrophil infiltration. At 72 hours, the changes observed were acinar necrosis, edema, fibrin deposition and inflammatory cell infiltration. Late changes were fibrinoid necrosis and fibroblast proliferation. In the acute phase, the histological changes in the lungs were congestion, focal pulmonary edema and intra-alveolar hemorrhages while, in the late stage, there was persistence of vascular congestion. The changes observed in the kidneys were vacuolization of tubular epithelium in the subcapsular region and areas of hemorrhage in the interstitium. Intestinal changes included degenerative changes in the villous epithelium in the acute phase with normalization of the histology in the late phase. CONCLUSION: Our findings correlate with the clinical observation of multisystem organ failure in acute pancreatitis. Early changes in these organs suggest that careful observation is mandatory in patients with acute pancreatitis in order to institute supportive treatment. PMID- 17873459 TI - Endoscopic ultrasound-guided fine needle aspiration and cyst fluid analysis for pancreatic cysts. AB - CONTEXT: Endoscopic ultrasound (EUS) with EUS-guided fine needle aspiration (EUS FNA) has been increasingly utilized to differentiate malignant/pre-malignant pancreatic cysts from those that are benign or have low malignant potential. OBJECTIVE: To determine the utility of EUS morphology, EUS-FNA cytology and cyst fluid analysis to distinguish mucinous cystic neoplasms from non-mucinous cystic neoplasms based on histopathology following surgical resection. DESIGN: A retrospective, single center case series. PARTICIPANTS: Patients who underwent EUS and EUS-FNA of known or suspected pancreatic cysts followed by surgical resection. The final diagnosis was based on histopathology. SETTING: Patients were divided in two groups: mucinous cystic neoplasms and non-mucinous cystic neoplasms. Patients with intraductal papillary mucinous tumors were excluded. MAIN OUTCOME MEASURES: Clinical profiles and EUS findings. RESULTS: Forty-eight patients (mean age: 52 years; 29 females, 19 males) were identified: 16 mucinous cystic neoplasms and 32 non-mucinous cystic neoplasms. There were more women in the mucinous cystic neoplasm group compared to the non-mucinous cystic neoplasm group (88% vs. 47%; P=0.011) but the two groups were otherwise similar. The sensitivity, specificity and frequency of cases correctly identified of EUS-FNA cytology for the diagnosis of mucinous cystic neoplasms were 12.5% (95% CI: 2.2 37.2%), 90.6% (95% CI: 75.0-97.5%) and 64.6% (95% CI: 50.4-77.0%), respectively. Median cyst fluid CEA for the mucinous cystic neoplasm group (277 ng/mL; n=14) was significantly higher (P=0.002) than the non-mucinous cystic neoplasm group (1.5 ng/mL; n=21). Cyst fluid CEA greater than 800 ng/mL had a sensitivity of 42.9% (95% CI: 21.3-67.4%) and specificity of 95.2% (95% CI: 75.6-99.9%) for the diagnosis of mucinous cystic neoplasm. On the other hand, a cyst fluid CEA greater than a best cut-off ranging from 3.5 to 8.5 ng/mL had a sensitivity of 92.9% (95% CI: 66.5-100%), a specificity of 66.7% (14/21; 95% CI: 45.2-83.0%), and an accuracy of 81.1% with a frequency of cases correctly identified of 77.1% (95% CI: 60.7-88.2%). CONCLUSIONS: EUS-FNA cytology and cyst fluid CEA greater than 800 ng/mL are insensitive but highly specific for differentiating mucinous cystic neoplasms from non-mucinous cystic neoplasms. EUS morphology alone cannot distinguish between the two groups. PMID- 17873461 TI - Rapid evolution from the first episode of acute pancreatitis to chronic pancreatitis in human subjects. AB - CONTEXT: Growing evidence suggests that recurrent acute pancreatitis leads to chronic pancreatitis, but this sequence is seldom reported in human subjects. The sentinel acute pancreatitis event hypothesis suggests that an initial episode of acute pancreatitis is the first step in a complicated series of events ultimately leading to chronic pancreatitis. OBJECTIVE: To identify patients who evolved from recurrent acute pancreatitis to chronic pancreatitis. SETTING: The Severity of Acute Pancreatitis Study (SAPS) database was reviewed. PATIENTS: Four out of 102 enrolled patients fulfilled the above sequence of events: progression from a single self-limited episode of acute pancreatitis to recurrent attacks to chronic pancreatitis proven by CT scan. However, not all 102 enrolled patients were followed with CT scans; hence there may be more patients with progression. RESULTS: In all four patients, upon initial presentation, there was no evidence of chronic pancreatitis on the CT scan performed and no clear acute pancreatitis etiology was identified. They were asymptomatic between recurrent attacks. All patients progressed to chronic pancreatitis over a relatively short period of time. Two patients were positive for SPINK1 mutations (N34S), and underwent pancreatectomy with pancreatic islet autotransplantation. CONCLUSION: The presented patients seem to fulfill the sentinel acute pancreatitis event hypothesis. Their clinical course supports the concept that pancreatitis may be an entity with a broad spectrum of end-points ranging from an isolated episode of acute pancreatitis evolving to chronic pancreatitis. PMID- 17873462 TI - Cannabinoid-induced pancreatitis: a case series. AB - CONTEXT: There is only one previously published case report of acute pancreatitis secondary to the use of tetrahydrocannabinoid. While drugs, in general, account for 2% of all the causes of acute pancreatitis, we add to the literature three additional cases of cannabis-induced pancreatitis. CASES: The first case occurred in a 22-year-old man who admitted to smoking tetrahydrocannabinoid heavily over the days prior to admission. The second case involved a 23-year-old man with multiple admissions for tetrahydrocannabinoid-induced pancreatitis. The third case involved a 20-year-old female who admitted to smoking tetrahydrocannabinoid heavily over a period of two weeks prior to admission. In all cases, other causes of pancreatitis were ruled out. Furthermore, the symptoms associated with the acute pancreatitis subsided upon discontinuation of the drug. CONCLUSION: Cannabis is the world's most popular illicit drug with over 4% of the world's population using it each year. Despite this, acute pancreatitis is a rarely reported adverse effect of cannabis use. This case series adds to the literature that cannabis does in fact cause pancreatitis and it may be dose related, although the exact mechanism remains unknown. PMID- 17873463 TI - Heterotopic pancreas as a leading point for small-bowel intussusception in a pregnant woman. AB - CONTEXT: Adult intussusception occurs infrequently and differs from childhood intussusception in its presentation, etiology and treatment. Diagnosis can be delayed because of its longstanding, intermittent, and non-specific symptoms, and most cases are diagnosed at emergency laparotomy. CASE REPORT: We present the diagnosis and management of our patient, a pregnant woman, who had adult intussusception due to a heterotopic pancreas. CONCLUSION: Although relatively rare, intussusception should be included in the differential diagnosis of small bowel obstruction. PMID- 17873464 TI - Heterotopic pancreas: report of two cases. AB - CONTEXT: Heterotopic pancreas is a congenital anomaly defined as pancreatic tissue occurring outside its normal anatomical location, lacking both anatomic and vascular connections. Ninety percent of heterotopic pancreata are found in the upper part of the gastrointestinal tract and clinical presentations show differences. CASE REPORTS: We present two different cases of heterotopic pancreas. One of them was a 56-year-old man noted to have a mass in the proximal duodenum during elective cholecystectomy for cholelithiasis. The mass was excised locally and primary duodenal repair was carried out. The second case was a 41 year-old man admitted to our hospital with an intestinal obstruction caused by a jejunal heterotopic pancreas; he was operated on under emergency conditions. Both patients' postoperative periods were uneventful. CONCLUSION: Resection of the heterotopic pancreas tissue-bearing area is advisable when the condition is encountered coincidentally at surgery, and surgical exploration should be done for all symptomatic patients, particularly in the absence of a histological diagnosis. PMID- 17873465 TI - Groove pancreatitis: a case report and review of literature. AB - CONTEXT: Groove pancreatitis is a rare type of segmental pancreatitis characterized by fibrous scars of the anatomic space between the dorsocranial part of the head of the pancreas, the duodenum, and the common bile duct. CASE REPORT: A 40-year-old man, with a past history of chronic alcohol consumption presented with epigastric pain radiating to the back and intermittent vomiting and a weight loss of 9 kg. A CT of the abdomen revealed swelling of the pancreatic head, a hypodense mass and duodenal wall thickening with luminal narrowing. Peripancreatic fluid and dense strands were also seen. Upper gastrointestinal endoscopy revealed an edematous, shiny, reddish raised mucosa having a polypoid appearance with narrowing of the second portion of the duodenum. Histological examination of the duodenal biopsy specimens showed preservation of the crypt-villus ratio, and the submucosa showed Brunner gland hyperplasia. These findings appeared consistent with the diagnosis of groove pancreatitis. Presently, the patient is on conservative medical management with analgesics, proton pump inhibitors and a pancreatic enzyme supplement. CONCLUSIONS: Groove pancreatitis often masquerades as pancreatic head carcinoma. This condition should be kept in mind when making the differential diagnosis between pancreatic masses and duodenal stenosis. In all cases of focal pancreatitis involving the head or uncinate process of the pancreas with involvement of the adjacent duodenum, the possibility of groove pancreatitis should be considered. PMID- 17873466 TI - EUS-FNA contribution in the identification of autoimmune pancreatitis: a case report. AB - CONTEXT: Autoimmune pancreatitis is a benign inflammatory disease of the pancreas which mimics pancreatic malignancy both clinically and radiologically. Autoimmune pancreatitis is presented as a diffuse enlargement of the pancreas and as a diffuse irregular narrowing of the main pancreatic duct. CASE REPORT: We report the endoscopic-ultrasound-guided (EUS-guided) fine needle aspiration (FNA) cytology features of a case with autoimmune pancreatitis. A 24-year-old woman with diabetes mellitus was admitted to our hospital after having painless jaundice for 15 days. She denied any alcohol consumption. The biochemical profile showed a marked elevation of bilirubin and hyperglycemia while gamma-GT and CA 19 9 levels were increased fivefold. The immunologic profile of the patient was negative. EUS revealed diffuse hypoechoic pancreatic enlargement (sausage-like appearance of the pancreas). EUS-FNA was performed and the smears were rich in inflammatory cells (mainly lymphoplasmacytes) with sparse epithelial cells lacking atypia, elements which show a strong correlation between the histopathological and cytological findings. The patient underwent steroid therapy which led to resolution of the clinical symptoms and imaging abnormalities within a month. CONCLUSION: The FNA-cytology findings in conjunction with clinical and EUS findings could potentially establish a diagnosis of autoimmune pancreatitis and exclude carcinoma, thus preventing pancreatic resection. PMID- 17873467 TI - Association of macroamylasemia and type I macro-creatine kinasemia. A case report. AB - CONTEXT: Macroenzymes are serum enzymes presenting a higher molecular mass than the corresponding enzymes normally found in physiologic conditions or specific diseases, causing falsely increased total serum enzyme levels. The occurrence of macroenzymes represents a rare event in clinical practice, leading to unnecessary and often invasive additional diagnostic procedures. Macroamylase and macro creatine kinase belong to this category and may generate diagnostic confusion in the differential diagnosis between acute pancreatitis and acute myocardial infarction. Until now, the association of macroamylase and macro-creatine kinase in the same patient has never been described. CASE REPORT: A 68-year-old female patient presenting with increased serum levels of creatinine kinase and amylase at admission. CONCLUSIONS: This article reports the association of macroamylase and macro-creatine kinase in the same patient for the first time. PMID- 17873468 TI - Successful partial pancreatotomy as a salvage procedure for massive intraoperative bleeding during head coring for chronic pancreatitis. Report of a case. AB - CONTEXT: Chronic pancreatitis is a continuous inflammatory disease of the pancreas resulting in scarring and fibrosis with consequent decline in exocrine and endocrine function. The inflammatory process leads to the development of a head mass, and strictures and stones in the pancreatic duct which present as pain, or loco regional complications such as duodenal obstruction and biliary obstruction. The gold standard for the treatment of pain and loco regional complications remains surgery, which is usually a combination of drainage and partial resection (coring). This can be hazardous due to adhesions, inflammation or portal hypertension. CASE REPORT: We report a case in which severe bleeding from the pancreatic duct was encountered during a Frey procedure. It was from the superior mesenteric vein/splenic vein confluence and would have warranted a Whipple procedure. CONCLUSION: We describe a pancreatotomy for exposure and control of the bleeding, with re-suturing of the cut pancreas and completion of the pancreaticojejunostomy. PMID- 17873469 TI - Pancreaticoureteral fistula following penetrating abdominal trauma. AB - CONTEXT: The main pancreatic duct can form a fistulous communication with another epithelium in the setting of prolonged inflammation, operative manipulation, or direct trauma. We present a rare complication of a pancreaticoureteral fistula following a trauma nephrectomy. CASE REPORT: A 17-year-old male who sustained a gunshot wound to the back arrived to our Emergency Room hyopotensive, tachycardic, and with free intraperitoneal fluid on focused assessment sonography for trauma (FAST) exam. He was taken to the operating room for an exploratory laporatomy where a left nephrectomy was performed to control active bleeding from the left renal hilum. Significant bleeding was also encountered at the portal venous confluence. After packing and damage control laparotomy, the periportal/pancreatic bleeding was controlled during a second procedure 6 hours later. After one month in the Intensive Care Unit with an open abdomen, a computed tomography (CT) scan revealed a fluid collection in the splenic fossa which was drained by catheter. Persistent drainage revealed a high amylase concentration (greater than 50,000 U/L). A fistulogram revealed interruption of the main pancreatic duct, and a fluid collection by the tail of the pancreas that was in communication with the left ureter. The patient's urine amylase was also elevated. The patient was treated non-operatively given the healing open abdomen and controlled fistula. He had an otherwise uncomplicated recovery. CONCLUSIONS: This is the second report of a pancreaticoureteral fistula in the literature. Treatment of this communication should be similar to that of other pancreatic fistulae. PMID- 17873470 TI - Isolated blunt duodenal trauma: delayed diagnosis and favorable outcome with "quadruple tube" decompression. AB - CONTEXT: Isolated blunt duodenal injury is a rare finding associated with high morbidity and significant mortality. The early identification of a duodenal injury is usually difficult, considering the anatomical location of the duodenum and lack of peritoneal signs and diagnostic delay is part of the clinical picture in most cases. CASE REPORT: A 43-year-old man was admitted to our hospital after a motor vehicle collision. At admission he underwent emergency surgery because of lower extremities fractures. Twelve hours later he started to complain an increasing abdominal pain; blood tests showed serum amylase up to 180 U/L and a CT scan demonstrated a perforation of the third duodenal portion. At laparotomy a Grade III injury of the duodenum was evident. The laceration was sutured and a "quadruple-tube" decompression was performed. The postoperative course was uneventful. One year after surgery he is well without any long-term complication. CONCLUSION: A high degree of suspicion is necessary for early diagnosis of blunt duodenal trauma and CT scan should be performed in case of all significant epigastric trauma. In most cases primary direct repair of duodenal wounds can be safely achieved and duodenal decompression via triple or quadriple tube technique is required to decrease the risk of duodenal fistula. PMID- 17873471 TI - An autopsy case of autoimmune pancreatitis. AB - CONTEXT: Autoimmune pancreatitis is an increasingly recognized type of chronic pancreatitis, but little is known about the long-term outcome of the disease. CASE REPORT: We report an autopsy case of autoimmune pancreatitis. The patient was an 81-year-old Japanese male. He was referred to our department with jaundice in February 1996. ERCP images revealed a severe stricture of the lower part of the common bile duct and irregular narrowing of the main pancreatic duct. A diagnosis of extrahepatic cholangiocarcinoma was made and endoscopic biliary drainage was performed. A stricture of the common bile duct and narrowing of the pancreatic duct had improved on ERCP images when a follow-up examination was performed in November 1998. He was followed up for chronic pancreatitis. The serum IgG and IgG4 levels were increased on serological examination. He died of interstitial pneumonia and congestive heart failure in May 2003. At the autopsy examination, fibrosis was found in the periductal, interlobular and intralobular parts of the pancreas. Focal atrophy of the acinar cells was also identified. There was little infiltration of inflammatory cells into the parenchyma or the stroma of the pancreas. These pathological findings were similar to those of 'conventional' chronic pancreatitis. CONCLUSION: We present an autopsy case of autoimmune pancreatitis which is a rare finding. PMID- 17873472 TI - The pancreas as an islet transplantation site. Confirmation in a syngeneic rodent and canine autotransplant model. AB - CONTEXT: The availability of islet transplantation is limited by both the number of donor pancreata and the number of islets required for successful transplantation. There is evidence that the liver presents a less than optimal environment for islets that contributes to short- and long-term beta cell destruction or failure. OBJECTIVE: It is our hypothesis that the pancreas is a suitable transplant site and may require fewer islets than standard sites such as the liver or kidney, and could lead to improvements in transplantation outcomes. METHODS: To test this hypothesis both a rodent and a canine model were used. Syngeneic rat islets were transplanted to the pancreas, liver, or kidney of Lewis rats. Fasting blood glucose levels were compared for three months as an index of islet function. Dogs received an islet autotransplant to a pancreatic remnant. Insulin and glucose concentrations were followed for six months. RESULTS: In the rat, normoglycemia was maintained with 600 islets transplanted in the pancreas in contrast to the liver (3,200 islets) or kidney (1,000-2,000 islets). Dogs remained normoglycemic after receiving an intra-pancreatic islet transplant (mean 7,640+/-3,600 islets). There was no evidence of pancreatitis or nutritional deficiency in either species. CONCLUSIONS: The pancreas should be considered as an islet transplant site. The pancreas is the native milieu for islets, and offers the advantage of requiring fewer islets than other conventional sites, thereby increasing the possibility that one donor pancreas may serve one or more recipients. PMID- 17873473 TI - Early identification of postoperative pancreatic fistula may reduce the risk of postoperative hemorrhage in pancreatic resected patients. PMID- 17873484 TI - Effect of renal failure on peak troponin Ic level in patients with acute myocardial infarction. AB - OBJECTIVES: Peak troponin Ic (cTnI) level could be influenced by renal function. We evaluated the effect of moderate to severe renal failure on peak cTnI level during acute myocardial infarction (AMI). METHODS: One hundred and twenty-five consecutive patients admitted to the coronary care unit of a university hospital in France for primary angioplasty during AMI were retrospectively studied. RESULTS: The correlations between peak cTnI level, peak creatine phosphokinase (CK) level, peak cTnI/peak CK ratio and creatinine clearance (CrCl) were assessed. The peak cTnI/peak CK ratio was considered in order to standardize the peak cTnI level with the extent of myocardial necrosis. There was no significant correlation between CrCl and peak CK (r = 0.01, p = 0.95), peak cTnI (r = -0.08, p = 0.38) or the peak cTnI/peak CK ratio (r = -0.14, p = 0.13). There was a trend towards higher peak cTnI in patients with moderate to severe renal failure. The peak cTnI/peak CK ratio did not significantly differ among patients according to CrCl stratification, whereas the ratio of log-transformed values was significantly higher in patients with moderate to severe renal failure. CONCLUSION: In patients with AMI, the peak cTnI level seemed to be influenced by renal function. PMID- 17873485 TI - Single-lead electrocardiographic variables in the detection of prior myocardial infarction with respect to Q-wave status and infarct age. AB - OBJECTIVES: Conventionally, the detection of prior myocardial infarction (MI) is based on QRS abnormalities, which may ignore non-Q-wave MI (NQMI). We aimed at finding automatically applicable quantitative ECG variables for diagnosing prior MI. METHODS: Body surface potential mapping (BSPM) was registered and automatically analyzed in 144 patients with prior MI and in 75 healthy controls. The MI was defined according to its age as recent or old, and Q-wave status as Q wave MI (QMI) or NQMI. RESULTS: The QRSSTT integral, the STT integral and the T wave apex amplitude applied in single, selected leads were found to be the optimal parameters in the detection of prior MI. The areas under the receiver operating characteristic curves (AUC) were 89% for each, and detection was equal in old and recent MI (AUCs from 87 to 90%), and in QMI and NQMI (AUCs from 88 to 90%). CONCLUSIONS: The quantitative, automatically applicable single-lead variables comprising ventricular repolarization was effective in detecting prior MI, irrespective of the time elapsed from MI or the Q-wave status. These variables could be suitable for population studies and health screening purposes and are applicable to automatic ECG diagnostics of prior MI. PMID- 17873486 TI - Prediction of early pulmonary artery stenosis after arterial switch operation: the role of intraoperative transesophageal echocardiography. AB - OBJECTIVES: To investigate prospectively the prediction of the neopulmonary stenosis (neo-PS) after arterial switch operation (ASO) for transposition of the great artery (TGA) with intraoperative transesophageal echocardiography (TEE). METHODS: Infants with TGA undergoing the ASO were prospectively studied over 5 years. The neo-PS was defined when the peak flow velocity was over 3 m/s at the neo main pulmonary artery (neo-MPA) after ASO by TEE (TEEPS). Catheterization was performed if estimated peak neo-PS pressure gradient was over 40 mm Hg by transthoracic echocardiography. Balloon angioplasty was tried first and surgical reoperation was reserved for those with failed angioplasty. RESULTS: In total 49 consecutive patients were enrolled into the cohort study. TEEPS was identified in 21 patients. For patients with TEEPS, freedom from reintervention was 28% at 1 year and 23% at 2 years. For patients without TEEPS, freedom from reintervention for PS was 92% at 1 year and 78% at 2 years. The time interval from ASO to reintervention was significantly shorter in patients with TEEPS than without TEEPS. Existence of TEEPS and non-Lecompte method were main risk factor for reintervention. CONCLUSION: The present study demonstrated that the application of intraoperative TEE for infants undergoing ASO is very helpful in predicting the development of early postoperative neo-PS. PMID- 17873487 TI - Serial hemodynamics and complications of pregnancy in severe pulmonary arterial hypertension. AB - We report a case of a woman who became pregnant after the diagnosis of moderate to severe pulmonary hypertension and underwent successful full-term pregnancy. Pulmonary hemodynamics were monitored before pregnancy and in the peripartum period. The patient was followed closely by the cardiology and high-risk obstetric specialists in the outpatient setting until she underwent c-section with epidural anesthesia. Outpatient medical management included twice daily subcutaneous enoxaparin and once daily amlodipine. Immediately prior to cesarian section, and for several days postoperatively, invasive hemodynamic monitoring was employed to titrate medical therapy. During delivery, strict attention focused on limiting intravenous fluids in order to avoid right ventricular volume overload. The postoperative course was complicated by a spontaneous, acute rise in pulmonary vascular resistance, which was managed with intravenous epoprostenol. In addition, abdominal bleeding, likely related to postoperative anticoagulation and platelet dysfunction, was controlled with transfusion and spontaneously resolved after discontinuing the anticoagulation. This case presents a favorable outcome in a pregnant patient undergoing cesarian section despite several complications related to pulmonary hypertension and right ventricular dysfunction, which are often fatal. PMID- 17873488 TI - Effects of bariatric surgery on early myocardial alterations in adult severely obese subjects. AB - OBJECTIVE: Aim of this study was to investigate the effect of weight loss on structural and functional myocardial alterations in severely obese subjects treated with bariatric surgery. PATIENTS AND METHODS: Thirteen severely obese patients (2 males and 11 females) were enrolled in the study. All subjects underwent conventional 2D color Doppler echocardiography. The new ultrasonic techniques used were: (a) integrated backscatter for the analysis of myocardial reflectivity, referred to pericardial interface as expression of myocardial structure (increase in collagen content) and of cyclic variation index as expression of intrinsic myocardial contractility and (b) color Doppler myocardial imaging (CDMI) for the analysis of strain and strain rate (myocardial deformability). All subjects underwent bariatric surgery and were resubmitted to echocardiographic and biochemical examination 6-24 months after surgery. RESULTS: The main finding of the present study was a quite complete normalization of myocardial functional and structural alterations after weight loss. In particular, the cyclic variation index at septum level improved from 14.6 +/- 7.0 before to 25.7 +/- 11.2 (means +/- SD) after surgery (controls: 36.2 +/- 9.1). Mean reflectivity at septum level significantly decreased from 55.8 +/- 9.5 to 46.5 +/- 8.8 (controls: 43.0 +/- 8.0). Also, the strain at septum level significantly improved after surgery (from -11.9 +/- 3.2 to -20.4 +/- 5.3; controls: -23.4 +/- 9). CONCLUSION: This study establishes: (a) the utility of new ultrasonic techniques to detect very early structural and functional myocardial alterations in severely obese patients, and (b) the regression of these subclinical abnormalities after weight loss achieved by bariatric surgery. PMID- 17873489 TI - Accuracy of N-terminal probrain natriuretic peptide to predict mortality or detect acute ischemia in patients with coronary artery disease. AB - OBJECTIVE: The aim of the study was to assess the accuracy of N-terminal probrain natriuretic peptide (NT-proBNP) to predict mortality or detect acute ischemia in patients with coronary artery disease (CAD). METHODS: This study included 1,552 patients with stable (n = 1,059) or unstable (n = 493) CAD undergoing percutaneous coronary intervention. NT-proBNP was measured before percutaneous coronary intervention. The primary endpoint of the study was mortality. Patients were followed for 3.6 years. RESULTS: There were 171 deaths (11%) during follow up. In the entire group of patients, NT-proBNP had the best accuracy to predict mortality (area under receiver operating characteristic curve 0.76, 95% CI 0.72 0.80). In patients without congestive heart failure (n = 760) there were 46 deaths (6%). The area under receiver operating characteristic curve of NT-proBNP was reduced to 0.70 (95% CI 0.63-0.79) which was not better than the area under curve of age (p = 0.981) or C-reactive protein (p = 0.082) regarding mortality. NT-proBNP showed limited power to detect patients with acute ischemia (area under curve 0.63, 95% CI 0.60-0.66) among consecutive patients with stable and unstable CAD. CONCLUSIONS: NT-proBNP has a moderate accuracy to predict mortality and does not assist in the diagnosis of acute myocardial ischemia in patients with CAD. PMID- 17873490 TI - Atrial fibrillation and antithrombotic therapy in a 75-year-old population. AB - AIMS: To find the true prevalence of diagnosed and undiagnosed atrial fibrillation (AF) in a population aged 75 years in 2 municipalities in Norway, and to study the use of antithrombotic therapy in this group. METHODS: All 1,117 citizens in Asker and Baerum municipalities in eastern Norway born in 1930 were invited to participate in a prevalence study of AF. Nine hundred and sixteen subjects (82%) were examined by electrocardiogram, and blood pressure and pulse rate were measured. Comorbidity and current medication were recorded. RESULTS: AF was present in 92 subjects (10%; 95% CI 8.2-12.1%), including 33 with ECG documented, paroxysmal AF. In addition, 8 subjects had a history of a single, transient episode of AF. AF was previously undiagnosed in 10 out of 916 (1.1%). In 77 of 82 patients with previously diagnosed AF (93.9%), antithrombotic therapy was compliant with international guidelines. CONCLUSION: Ten percent (95% CI 8.2 12.2%) in this 75-year-old population had AF. Compliance with international guidelines regarding antithrombotic therapy was high. Previously undiagnosed AF was found in only 10 out of 916 (1.1%). PMID- 17873491 TI - Litigation in nontraumatic aortic diseases--a tempest in the malpractice maelstrom. AB - OBJECTIVES: Physicians are vulnerable to highly litigated thoracic aortic diseases. On the basis of a review of litigated cases, we aim to determine legally protective strategies for physicians and methods to improve treatment. METHODS: Thirty-three nontraumatic, thoracic aorta-related legal cases were analyzed. RESULTS: Twenty-three patients (69.7%) had dissections (21 ascending, 2 descending), 8 (24.2%) had aneurysms and 2 had miscellaneous other phenomena (1 coarctation and 1 iatrogenic descending aortic rupture). The adverse event was death in 30 (90.9%) patients and paraplegia or stroke in 3 (9.1%). Allegations included: failure/delay in diagnosis (19), delay in surgery (4), error in surgical technique (5), failure to prevent paraplegia (2) and miscellaneous (3). Medical treatment was retrospectively judged suboptimal in 22 cases (66.6%) for reasons consonant with allegations. CONCLUSIONS: Aortic disease can be diagnostically elusive, as 'the great masquerader'. Emergency physicians must maintain a high index of suspicion for aneurysm and dissection. The D-dimer test can effectively rule out aortic dissection. 'Triple rule-out' CT scans should be performed liberally. CT scan readers must remember to evaluate the aorta. Operating room administrators must be aware that postponing a scheduled thoracic aortic case may result in interim rupture and consequent litigation. With virulent thoracic aortic diseases, adverse outcome itself does not imply substandard care. PMID- 17873492 TI - Clinical and hemodynamic effects of bosentan dose optimization in symptomatic heart failure patients with severe systolic dysfunction, associated with secondary pulmonary hypertension--a multi-center randomized study. AB - OBJECTIVE: To evaluate the effects of bosentan on echo-derived hemodynamic measurements, and clinical variables in symptomatic heart failure (HF) patients. METHOD: Multi- center, double-blind, randomized (2:1), placebo-controlled study comparing bosentan (8-125 mg b.i.d.) to placebo in patients with New York Heart Association class IIIb-IV HF, left ventricular ejection fraction <35% and systolic pulmonary artery pressure (SPAP) >40 mm Hg. Primary and secondary endpoints were change from baseline to 20 weeks in SPAP and cardiac index, respectively. Safety endpoints were treatment emergent adverse events (AEs), change in body weight, hemoglobin, hematocrit, systolic blood pressure and diuretic use. RESULTS: Ninety-four patients enrolled: 60 to bosentan, 34 to placebo. There was no significant difference between the 2 arms in SPAP change (0.1 +/- 11.5 mm Hg , 95% confidence limit (CL) -5.4 to 5.2, p = 0.97), cardiac index shift (0.12 +/- 0.45, 95% CL -0.09 to 0.33 , p = 0.24 ) or any of the other 22 echocardiographic measurements obtained. Therapy-duration was longer in the placebo arm, while more patients in the bosentan arm experienced adverse and serious AEs. CONCLUSION: In HF patients with left ventricular dysfunction and secondary pulmonary hypertension, bosentan did not provide any measurable hemodynamic benefit, and was associated with more frequent AEs, requiring drug discontinuation. PMID- 17873493 TI - Radiographic evaluation of children with growth disorders. AB - Short stature as well as tall stature can have a wide variety of causes. Tall stature is usually experienced as a less important problem than short stature, but for both clinical presentations it is important to make a correct diagnosis as to etiology. The identification of the diagnosis frequently relies on radiological criteria. However, no international uniformity exists with respect to the radiographic evaluation of children with growth problems. We recommend that in patients with a possible diagnosis of a skeletal dysplasia a skeletal survey must be performed. In patients with a proportionate stature, radiographic analysis of the hand and wrist will be sufficient in most cases. However, whenever there are clinical abnormalities with a possible underlying bone anomaly, a modified skeletal survey is appropriate. The combination of clinical and biochemical features and an appropriate skeletal survey can often lead to the correct diagnosis and/or guide the subsequent molecular analysis. PMID- 17873494 TI - Influence of vigilance and learning on prefrontal activation in schizophrenia. AB - BACKGROUND: Executive functions, which are neuroanatomically associated with the frontal lobe, are known to be impaired in schizophrenia. It is, however, still unclear whether the underlying functional disturbance is due to a hyper- or a hypoactivation of the dorsolateral prefrontal cortex (DLPFC) or neither. METHODS: To address this question, we examined the brain activation of 21 schizophrenic patients on atypical antipsychotic medication and 21 healthy control subjects during a mental maze task by means of fMRI. RESULTS: We found no significant overall difference in cerebral activation between the groups, but differences in the change in DLPFC activation from the first to the second half of the experiment. In the maze compared to the control task, there was a decrease in activation in the DLPFC in the patients and an almost significant increase in the controls. The change in activation in the patient group correlated with a change in subjective sleepiness, while the increase in activation in the controls could be attributed to learning processes. CONCLUSION: We hypothesized that differential temporal influences on brain activation could lead to either hyper- or hypoactivation of the DLPFC in schizophrenia. PMID- 17873495 TI - Exaggerated beat-to-beat R amplitude variability in patients with panic disorder after intravenous isoproterenol. AB - BACKGROUND: Anxiety symptoms are associated with a marked increase in sudden cardiac death, suggesting an abnormality in cardiac autonomic function. Our previous studies show a relationship between R amplitude variability and sympathetic function. METHODS: We examined the effects of beta-adrenergic stimulation on R and T amplitude variability in panic disorder patients by infusing the beta-adrenergic agonist isoproterenol in 6 panic disorder patients and 11 normal subjects. The ECG signal was analyzed before the infusion and 5 min after the infusion was started. The outcome measures were the R and T detrended variance normalized for mean amplitudes (R(vm) and T(vm)) and the R(vi) and T(vi), measures which are normalized for the inter-beat interval variability in addition. RESULTS: Patients with panic disorder had significantly more variability in R and T amplitude than normal controls and the R amplitude variability was increased further by beta-adrenergic stimulation with isoproterenol, which was more pronounced in the patients. CONCLUSIONS: The isoproterenol-associated increase in R amplitude variability occurred in controls in the absence of significant anxiety. However, the increase in R amplitude variability was greater in patients with panic disorder, suggesting a greater sensitivity to beta-adrenergic effects of isoproterenol or to isoproterenol induced anxiety. PMID- 17873496 TI - Depressive symptoms are related to decreased low-frequency heart rate variability in older adults with decompensated heart failure. AB - BACKGROUND/AIMS: Depression has been associated with increased mortality among individuals with heart failure, but the mechanism for this association is unsettled. Depression is often found to result in autonomic dysfunction which, if present in heart failure, might help explain worsened outcomes. METHODS: This study was a cross-sectional evaluation of the relationship between depressive symptoms and cardiac autonomic function, as assessed by short-term heart rate variability (HRV) analysis in aged patients with acute/decompensated heart failure of coronary origin (CHF). A 21-item Hamilton Depression score and measures of short-term HRV were obtained in 31 inpatients >or=65 years of age, 24 72 h after admission to the coronary care unit with a diagnosis of CHF. RESULTS: Clinical depression was present in 22.6% of participants. In the sample as a whole, increasing depressive symptoms were associated with decreased low frequency HRV. CONCLUSION: These results may be important in light of recent indications that decreased low-frequency HRV is a predictor of mortality in patients with heart failure. PMID- 17873497 TI - Interferon-alpha influences tryptophan metabolism without inducing psychiatric side effects. AB - BACKGROUND: Interferon-alpha (IFN-alpha) treatment is often associated with psychiatric side effects and has been found to lower the amount of tryptophan (TRP) available to the brain. The alterations in tryptophan metabolism might underlie the psychiatric side effects during treatment with IFN-alpha. METHODS: In this study, 43 oncology patients treated with IFN-alpha were included. In order to study de novo depressions, depressed patients at baseline were excluded. Psychiatric evaluation comprising clinical judgment combined with a structured psychiatric interview and observer-based and self-report rating scales was performed at baseline and at 4 weeks, 8 weeks and 6 months after the start of treatment with IFN-alpha, and in the case of emerging psychopathology. Blood samples were drawn at the same evaluation times and assessed for concentrations of TRP, large neutral amino acids, kynurenine, 5-hydroxyindole acetic acid, neopterin and biopterin. RESULTS: During treatment with IFN-alpha, several alterations in laboratory parameters occurred that were consistent with an increased degradation of peripheral TRP. Psychometric ratings revealed hardly any psychiatric changes. No consistent associations were found between changes in the laboratory assessments determined and the diverse psychiatric measures. CONCLUSION: In this study, IFN-alpha was found to alter TRP metabolism without inducing psychiatric side effects. Therefore, a possible relationship between TRP metabolism and depression was not substantiated by this study. PMID- 17873498 TI - Optimizing management of recurrent epithelial ovarian cancer: a critical need for evidence-based data. PMID- 17873499 TI - Octreotide in the management of chemoradiotherapy-induced diarrhea refractory to loperamide in patients with rectal carcinoma. AB - OBJECTIVE: To evaluate the efficacy of octreotide in the treatment of chemoradiotherapy (CRT)-induced diarrhea (CRTID) refractory to conventional loperamide treatment in this pilot study. METHODS: Forty-two rectal carcinoma (T(3-4)N(0-2)M(0)) patients with grade 2 or 3 diarrhea refractory to loperamide were enrolled to receive octreotide. Eligible patients were treated with pelvic radiotherapy combined with bolus 5- fluorouracil CRT. Octreotide was administered subcutaneously, 150 microg three times daily, for 5 consecutive days. Only complete resolution of diarrhea was considered as therapeutic success. RESULTS: Diarrhea mainly occurred in the first 4 weeks of CRT (83.3%) and completely resolved in 34 patients (80.9%) following octreotide administration. Mean time to response was 2.7 days: 27 patients (64%) responded during the first 3 days, and the remaining 7 (17%) on days 4 and 5. No significant side effect was reported. Eight patients (19.1%) with refractory diarrhea were hospitalized for additional treatment. No treatment delay was reported in complete responders, whereas an average 7.7-day delay was observed in refractory patients. Antidiarrheal treatment was administered on an outpatient basis in the response group, whereas refractory patients were hospitalized for an average of 8.8 days. CONCLUSION: Daily subcutaneous octreotide administration (150 microg t.i.d.) for 5 days is apparently an effective, tolerable treatment modality for concurrent CRTID refractory to loperamide. PMID- 17873500 TI - [Hemodynamic effects of local anesthetics with adrenaline during septal surgery]. AB - OBJECTIVES: We investigated the hemodynamic effects of local anesthetics with adrenaline used before septal surgery. PATIENTS AND METHODS: In a prospective, controlled design, administration of local anesthetics was performed with and without adrenaline in 39 patients and 10 patients, respectively, undergoing septal surgery. Plasma adrenaline concentrations were measured before anesthesia, and after 2, 5, and 10 minutes from anesthesia. The patients were monitored with respect to pulse rate, electrocardiographic findings, and blood pressure. RESULTS: Preoperative plasma adrenaline levels were similar in patients receiving local anesthetics with or without adrenaline (0.8 nmol/l vs 0.7 nmol/l). Following adrenaline administration, adrenaline levels showed significant increases to 2.2, 1.9, and 1.7 nmol/l after 2, 5, and 10 minutes, respectively (p<0.001), whereas they remained similar in the control group. No side effects related to adrenaline use were detected. CONCLUSION: Despite systemic absorption of local injections, adrenaline-related side effects during septal surgery are extremely rare when the patients are closely monitored. PMID- 17873501 TI - [Adenoidal vegetations in adults: an evaluation of 12 cases]. AB - OBJECTIVES: We evaluated the clinical significance of adenoidal vegetations which are overlooked as a cause of nasal obstruction in adults. PATIENTS AND METHODS: The study included 12 patients older than 15 years of age (10 males, 2 females; mean age 23.5 years; range 15 to 32 years) who presented with nasal obstruction due to adenoidal vegetations. The patients were evaluated with respect to age, sex, complaints, findings of physical examination, computed tomography of the nasopharynx, and nasal endoscopy, and histopathologic results. RESULTS: All the patients had nasal obstruction. The most common symptom was snoring. Physical examination showed a vegetative mass in the posterior wall of the nasopharynx obstructing the choana. Five patients had bilateral serous otitis media and eight patients had postnasal purulent drainage. All the patients underwent adenoidectomy under general anesthesia and with transnasal endoscopic control. Histopathologic examination of surgical specimens showed lymphoid hyperplasia. CONCLUSION: Although adenoidal tissue undergoes regression toward the adolescent period, it may present as the chief cause of nasal obstruction in adults. PMID- 17873502 TI - Oncological results of surgical treatment of malignant tumors of the nasal vestibule. AB - OBJECTIVES: We evaluated functional results of surgical treatment for squamous cell carcinoma of the nasal vestibule. PATIENTS AND METHODS: A retrospective review of 2,763 patients treated for head and neck cancers between 1991 and 2000 revealed 10 cases of nasal vestibule tumors, with an incidence of 0.36%. All the patients were males with a mean age of 64.8 years (range 58 to 72 years). Based on the classification system of the AJCC 1992 for skin cancers, and the UICC classification for neck metastasis, three patients had T2, three patients had T3, and four patients had T4 tumors. Lymph node metastasis was present in three patients. Nine patients were treated with surgery as the primary treatment. One patient underwent surgical salvage following radiotherapy failure. The mean follow-up period was 3.65 years (range 6 months to 12 years). RESULTS: Three patients with metastatic neck disease and four patients with advanced tumors underwent radical neck dissection and selective supraomohyoid neck dissection, respectively. Seven patients underwent reconstruction with paramedian forehead flap (n=3), nasolabial flap (n=2), aural composite graft, or split thickness flap. Including the one with radiotherapy failure, two patients died within the first postoperative year due to local and neck recurrences. Another patient died in the postoperative third year due to metastatic squamous cell carcinoma of the lung. No cosmetic or functional complaints were observed in patients with early stage lesions. Two patients with advanced tumors had nasal ventilation problems and a secondary revision procedure was required in one. CONCLUSION: Surgery is a successful therapeutic modality for carcinoma of the nasal vestibule, especially when applied in conjunction with proper reconstruction techniques and, when necessary, neck dissection procedures. PMID- 17873503 TI - [The validity of the Rhinosinusitis Disability Index in chronic sinusitis]. AB - OBJECTIVES: Quality of life in patients with chronic rhinosinusitis is affected more than many other chronic diseases. In this study, we evaluated the validity of the Rhinosinusitis Disability Index (RSDI) in assessing deterioration in the quality of life. PATIENTS AND METHODS: The Rhinosinusitis Disability Index consisting of 30 items was administered to 355 patients (206 males, 149 females; mean age 41 years; range 21 to 57 years) with chronic rhinosinusitis before and after treatment and to 112 healthy controls (44 males, 68 females; mean age 35 years; range 18 to 48 years). A detailed history was taken from the patients and skin-prick test was performed to eliminate allergic rhinitis. The scores of patients and physicians were compared. The score of the RSDI is inversely proportional to the quality of life. RESULTS: Spearman rank correlation test yielded a coefficient of 0.42 for comparisons between pre- and post-treatment scores and physician evaluation. Coefficients for correlations between the patients' and physicians' scores before and after treatment were 0.62 and 0.59, respectively. The mean RSDI scores of the patients before and after treatment were 35.2+/-14.3 and 13.9+/-10.8, respectively, compared to a score of 8.4+/-8.8 of the control group. Only 72.4% of the patients could answer the questions by themselves. CONCLUSION: If properly administered, the RSDI is a reliable method in evaluating quality of life; however, it is affected by the socioeconomic and education levels of the participants. PMID- 17873504 TI - [Arterial blood gas abnormalities during attacks of dizziness]. AB - OBJECTIVES: We investigated arterial blood gas abnormalities in patients presenting with dizziness. PATIENTS AND METHODS: The study included 58 patients (39 females, 19 males; mean age 46 years; range 22 to 74 years) who presented during attacks of dizziness. The duration of vertigo complaints ranged from one day to 30 years. Arterial gas measurements were performed at presentation and one month after treatment. The patients were examined in five groups according to the diagnoses: Meniere's disease (n=14), benign paroxysmal positional vertigo (n=13), vertebrobasilar insufficiency (n=12), vestibular neuritis (n=4), and craniocervical myofascial syndromes (n=15). RESULTS: At presentation, pH was low (acidosis) in two patients (3.5%), and high (alkalosis) in 15 patients (25.9%). After treatment, all abnormal pH values returned to normal. Twenty-four patients had high or low HCO3- values. High HCO3- values persisted in three patients together with dizziness. Patients with vestibular neuritis had significantly higher PO2 values compared to those with craniocervical myofascial syndrome and vertebrobasilar insufficiency (p<0.05). However, one month after treatment, there were no significant differences between five groups with respect to PO2 levels (p>0.05). Consecutive blood gas measurements did not differ significantly within each diagnosis group (p>0.05). CONCLUSION: Our results suggest that arterial blood gas abnormalities may be related to vertigo attacks. PMID- 17873505 TI - Serum nitric oxide levels in patients with head and neck squamous cell carcinoma. AB - OBJECTIVES: We determined serum nitric oxide (NO) levels in patients with head and neck squamous cell carcinoma (SCC) and sought correlations with TNM staging, tumor localization, and tumor grade. PATIENTS AND METHODS: Serum samples were obtained from 36 patients (mean age 63 years; range 37 to 80 years) with head and neck SCC prior to treatment and from 20 healthy individuals (mean age 56 years; range 30 to 72 years) as controls. Tumor staging was based on the criteria of the American Joint Committee of Cancer staging system in 2002. Thirteen patients had stage I-II, and 23 patients had stage III-IV tumors and all had well- or moderately-differentiated SCC (grade 1-2). Serum NO levels were analyzed by a spectrophotometric method based on the determination of total nitrite levels in serum and compared between the patient and control groups. RESULTS: The mean serum NO levels were 20.08+/-1.40 micromol/l and 13.57+/-0.99 micromol/l in cancer patients and controls, respectively (p=0.001). There were no correlations between NO levels and age, sex, tumor stage, localization, and histological grade. CONCLUSION: These data suggest that head and neck SCC is associated with increased serum NO levels, which may play a role in tumor growth. PMID- 17873506 TI - [Evaluation of patients with adult acute epiglottitis]. AB - OBJECTIVES: We evaluated adult patients who were treated for acute epiglottitis. PATIENTS AND METHODS: The study included five adult patients who were diagnosed as having acute epiglottitis during an eight-month period. All the patients were males with an age range of 38 to 54 years, except for a 77-year-old patient. The Friedman staging system was used to evaluate the severity of dyspnea and symptoms. Treatment was comprised of parenteral steroids and antibiotic therapy. The mean follow-up was one year (range 11 to 17 months). RESULTS: The main presenting symptom was moderate to severe dyspnea in all the patients, which was rated as stage 4 in one patient, stage 3 in two patients, and stage 2 in two patients. Diagnoses were made by laryngoscopic examination and lateral radiograms of the neck, which showed the thumb sign in all the patients. Computed tomography of the neck revealed an epiglottic abscess in one patient. One patient required tracheotomy. All the patients benefited from parenteral steroid and antibiotic treatment, with relief of dyspnea and difficulty in swallowing. The mean hospitalization was 5.6 days (range 3 to 8 days). No recurrences were observed during the follow-up period. CONCLUSION: Acute epiglottitis in adult patients requires a timely and correct diagnosis and prompt appropriate treatment. A tracheotomy should not be avoided when necessary. PMID- 17873507 TI - Comparison of different methods of circumferential tracheal reconstruction: an experimental study. AB - OBJECTIVES: This study was designed to compare different prefabrication models for circumferential tracheal reconstruction. MATERIALS AND METHODS: Thirty adult female New Zealand rabbits were divided into six groups for circumferential tracheal reconstruction with a different tissue combination. Prefabrication of neotrachea was performed without anastomosis. Lateral thoracic fascia or pectoralis major muscle were used for vascular supply. Polypropylene mesh, polytetrafluoroethylene (Gore-Tex), or cartilage rings were used for skeletal framework. Hairless epithelial skin graft was used for inner lining. The groups were compared in terms of viability of hairless epithelial graft, longitudinal flexibility, rigidity, flap wall thickness, internal diameter, and flap viability. RESULTS: Epithelial skin graft was almost totally viable (95%-99%) in the polypropylene mesh groups. Gore-Tex groups exhibited almost total necrosis (74%-71%). Longitudinal flexibility and rigidity were similar to the native trachea in Gore-Tex and polypropylene mesh groups. Neotrachea prefabricated with cartilage grafts showed more than normal longitudinal flexibility and collapsed easily. CONCLUSION: The prefabricated model with the use of polypropylene mesh for skeletal framework and lateral thoracic fascia for vascular supply seems to be the best alternative in the reconstruction of circumferential tracheal defects. PMID- 17873508 TI - [Epithelial-myoepithelial carcinoma of the submandibular gland: a case report]. AB - Epithelial-myoepithelial carcinomas are rare, low-grade, malignant salivary gland tumors. They are mostly seen in the parotid gland. The submandibular gland is a rare localization. A 54-year-old woman presented with a painless lump on the left side of the neck. Examination showed a mass with smooth surface in the left submandibular region. Fine needle aspiration cytology of the mass was reported as malignant epithelial tumor metastasis. Computed tomography of the neck showed left submandibular gland hypertrophy. Left submandibular gland excision with functional neck dissection was performed. The histopathological diagnosis was epithelial-myoepithelial carcinoma of the submandibular gland with one lymph node metastasis. PMID- 17873509 TI - Neurofibromatosis type 2 associated with multiple cranial nerve schwannomas: a case report. AB - A 16-year-old male patient complained of right-sided tinnitus and mild deafness of one-month history. He also had a family history of neurofibromatosis type 2 and a history of a prior operation for left vestibular schwannoma a year ago. Otoneurologic examination revealed moderate sensorineural hearing loss. Magnetic resonance imaging demonstrated multiple extra-axial enhancing masses in the vicinity of both hypoglossal nerves, the right vestibular nerve, the left vestibular nerve, the right trigeminal, the left occulomotor, and the right abducens nerves. These findings were evaluated as multiple cranial nerve schwannomas. The case was considered a rare manifestation of neurofibromatosis type 2 without any concomitant abnormality in the central nervous system. Symptomatic medical treatment was initiated and the patient was referred to the neurosurgery department. PMID- 17873510 TI - An alternative surgical approach for sublingual dermoid cysts: a case report. AB - A 52-year-old woman presented with a painless swelling in the floor of the mouth. She stated that it had existed there for 40 years and had undergone a gradual enlargement within the past year. Examination showed a mass, 5x4 cm in size. An aspiration from the lesion revealed a cyst. The lesion was removed by a U-shaped superior based flap. Histopathological examination showed stratified squamous epithelium lining the cystic lumen. This technique can be an alternative approach in such lesions because it protects the oral mucosa by providing good exposure, and prevents injury to the lingual nerve and submandibular duct. PMID- 17873511 TI - Endoscopic endonasal-transantral surgery for an isolated orbital floor blow-out fracture in a pediatric patient. AB - Orbital floor blow-out fractures occur due to blunt trauma causing displacement of orbital contents to the maxillary sinus while the orbital rim is intact. Surgical repair of these fractures includes transantral, transorbital, or endoscopic endonasal approaches with or without implant use. We report a 12-year old boy who presented with diplopia after blunt trauma to the head while playing football. Computed tomography revealed a left isolated orbital blow-out fracture. The patient was treated by a combined endoscopic endonasal-transantral approach and stability was restored with a urethral balloon catheter following endoscopic reduction of the fracture. Healing of the orbital floor was confirmed by an early computed tomography scan. This technique restores eye volume and function without the use of external incisions or implants. PMID- 17873512 TI - Incudostapedial rebridging ossiculoplasty with glass ionomer cement: a case report. AB - A 31-year-old woman presented with a complaint of hearing loss of a two-year history. Otoscopic examination revealed a central ear drum perforation without discharge. The air-bone gap was 35 dB at 0.5, 1, 2, and 3 kHz. Under general anesthesia, the patient underwent tympanoplasty for chronic otitis media. At surgery, the ossicular chain was intact except for discontinuity by a 2-mm gap between the long process of the incus and the head of the stapes. The gap was reconstructed with the use of a fluoroplastic prosthesis. Myringoplasty was successful, but the patient complained of hearing loss at the end of six months. Transcanal posterior tympanotomy was performed under local anesthesia for decreased conductive hearing. The prosthesis was still in place, but was not conducting the movements of the malleus to the stapes. It was removed and glass ionomer cement (Ketac-Cem) was applied for rebridging. The average air-bone gap measured in the postoperative sixth month was less than 10 dB. PMID- 17873513 TI - A novel vacuolar myopathy with dilated cardiomyopathy. AB - We report a 46-year-old male patient with late-onset vacuolar myopathy and dilated cardiomyopathy. Acid maltase activity of the muscle was normal, but the biopsied muscle specimen stained for lysosome-associated membrane protein-2 (LAMP 2), which has recently been reported to be deficient in muscles of patients with Danon disease. The clinical features of the patient are distinct from X-linked myopathy with excessive autophagy, infantile autophagic vacuolar myopathy and autophagic vacuolar myopathy with late-onset and multiorgan involvement (Kaneda). PMID- 17873514 TI - Expression profiling reveals dysregulation of cellular cytoskeletal genes in HBx induced hepatocarcinogenesis. AB - The molecular mechanisms underlying hepatitis B virus encoded HBx protein mediated tumorigenesis are not fully understood. In order to gain a better view of the effects of HBx on transcriptional regulation and hepatocarcinogenesis, the expression profiles of liver and tumor tissues from 6- and 18-month-old p21-HBx transgenic and control mice were monitored using oligo microarrays. Data analysis demonstrated that 42 genes were deregulated in both 6- and 18-month-old HBx transgenic mouse tissues. Gene ontology assisted analysis classified these genes into functionally related clusters that encode proteins related to metabolism, signal transduction, transcription regulation and stress responses. Among them, cytoskeletal genes, including microtubule genes tubulinbeta2 (Tubb2), tubulinbeta3 (Tubb3) and tubulinbeta6 (Tubb6), intermediate filament genes periplakin, keratin 8 (K8) and keratin 18 (K18) and actingamma1 (Actg1), were closely clustered and upregulated in liver tissues. These results were validated by semi-quantitative RT-PCR in both mouse and human HCC tissues. The upregulation of K8 and K18 was only detected in p21-HBx but not p21-HBsAg liver tissues, suggesting that the global change in the expression of cellular cytoskeletal genes was correlated with the expression of HBx transgene. These findings propose for the first time that systemic dysregulation of cellular cytoskeletal genes is involved in HBx-induced hepatocarcinogenesis. PMID- 17873515 TI - Irinotecan chemotherapy during valproic acid treatment: pharmacokinetic interaction and hepatotoxicity. AB - PURPOSE: Because of its supposed inhibiting capacities of uridine-diphosphate glucuronosyltransferase 1A (UGT1A)-mediated glucuronidation in rats, the antiepileptic drug valproic acid has been investigated as modulator of irinotecan induced delayed-type diarrhea in rats. Here, we report on the pharmacokinetic and pharmacodynamic effects of this combination in a cancer patient. EXPERIMENTAL DESIGN: A patient who used valproic acid was administered irinotecan (600 mg). To investigate dose-limiting hepatotoxicity encountered during the first course, which was clinically attributed to a supposed higher exposure to the active irinotecan metabolite SN-38, valproic acid was tapered off. Blood samples for pharmacokinetic purposes were drawn during a course with and a course without concomitant valproic acid. Plasma-levels of irinotecan, SN-38, and SN-38G were determined using HPLC-assays. RESULTS: When irinotecan was combined with valproic acid, the exposure to SN-38 was 41% lower. Additionally, reversible elevations of the liver enzyme tests were noted. In particular, seven days after irinotecan administration gammaGT and transaminase levels raised up to 5.3-11.3 times the ULN (CTCAE grade 3). CONCLUSIONS: Valproic acid-induced plasma protein binding displacement and/or metabolic modulation of enzymes and drug transporters involved in irinotecan disposition may explain the reduced exposure to SN-38 in the presence of valproic acid. Given the herewith-coupled potential undertreatment, patients should firstly switch to another antiepileptic drug not known to interfere with irinotecan treatment. Additionally, this particular combination should not be implemented in clinical studies without simultaneously adjusting the irinotecan dose, and the risk of (severe) hepatotoxicity should be considered when designing protocols studying valproic acid (as histone deacetylase-inhibitor) in combination with other (anticancer) drugs. PMID- 17873516 TI - Raf inhibitor stabilizes receptor for the type I interferon but inhibits its anti proliferative effects in human malignant melanoma cells. AB - Interferon alpha (IFNalpha) is widely used in treatment of malignant melanoma patients. This cytokine acts on cells by engaging Type I IFN receptor consisting of two subunits, (IFNAR1 and IFNAR2) followed by activation of Janus kinases (Jak). Levels of IFNAR1 (regulated via degradation mediated by the betaTrcp E3 ubiquitin ligase) and IFNalpha signaling were reduced in 1205Lu melanoma cell line that harbors activated BRAF and exhibits high levels of betaTrcp ubiquitin ligase. Expression of stabilized IFNAR1 in melanoma cells decreased their tumorigenicity. Furthermore, RNAi-mediated BRAF knockdown and pharmacologic inhibition of either Raf or MEK1 decreased levels of betaTrcp and stabilized IFNAR1. However, despite causing stabilization of IFNAR1, Raf inhibitor BAY 43 9006 interfered with cellular responses to IFNalpha most likely due to its ability to directly inhibit Jak activity. We discuss the implications of this result for combination therapy with BAY 43-9006 and IFNalpha in melanoma patients. PMID- 17873517 TI - Indomethacin enhances the cytotoxicity of recombinant human lymphotoxin alpha on tumor cells by suppressing NFkappaB signaling. AB - Indomethacin is widely used to treat inflammatory and prevent adverse events which frequently accrue in biotherapy. In phase I clinical trial of recombinant human lymphotoxin alpha (rhLTalpha), indomethacin was premedicated to alleviate chill and fever. However, it is unknown whether indomethacin influences the therapeutic efficacy of rhLTalpha. In this study we found that pre-treatment with low dose of indomethacin enhanced the cytotoxicity of rhLTalpha and/or cisplatin/adriamycin on human tumor cells. Further investigation demonstrated that indomethacin dose-dependently suppressed the activation of nuclear factor kappa B (NFkappaB) by inhibiting phosphorylation and degradation of IkappaBalpha. In addition, indomethacin decreased the expression of NFkappaB-regulated gene products involved in rhLTalpha-induced anti-apoptosis (XIAP, cFLIP and cIAP-1), which may explain its sensitization of tumor cells to rhLTalpha and/or cisplatin/adriamycin. PMID- 17873518 TI - Bone marrow renin-angiotensin system expression in polycythemia vera and essential thrombocythemia depends on JAK2 mutational status. AB - Recent observations raise possibility for constitutively active, mutated JAK2 to modulate expression of RAS genes in CMPD. We analyzed the expression of AGT, renin, AT2R1 and ACE genes in normal and bone marrows of PV and ET patients with the respect to the presence of V617F JAK2 mutation. PV and ET had different expression patterns of major RAS components compared to normal BM which was primarily associated with the JAK2V617F mutation and less with PV or ET disease phenotype. However, AT2R1 was exclusively markedly upregulated only in PV, while ET showed moderate expression irrespective of the JAK2 mutational status. PMID- 17873519 TI - Take your "M" time. AB - Both entry and exit from mitosis are driven through the fine modulation of Cdk1 activity by several proteins or protein complexes. It is well established that to entry into the M-phase a cell requires Cdk1 to be fully activated in the nucleus by the Cdc25A, B and C phosphatases. Then, at the onset of anaphase Cdk1 activity suddenly drops mainly due to Cyclin B1 degradation, thus allowing exit from M phase. Recent data demonstrate that high Cdk1 activity is necessary also for proper chromosome segregation, since its premature drop determines acceleration of the progression from prophase to metaphase eventually with incorrect division of the DNA content. A primary role in maintaining high Cdk1 activity during prophase and metaphase is played by Cdc25C phosphatase. During the M-phase, the activity of Cdc25C is regulated by the FEZ1/LZTS1 (LZTS1) tumor suppressor gene, which is able to prevent Cdc25C degradation in mitotic cells. As a consequence, Lzts1 absence in mice results in accelerated mitotic progression, improper chromosome segregation and, eventually, in increased incidence of both spontaneous and carcinogen-induced cancer formation. PMID- 17873520 TI - Examples of mathematical modeling: tales from the crypt. AB - Mathematical modeling is being increasingly recognized within the biomedical sciences as an important tool that can aid the understanding of biological systems. The heavily regulated cell renewal cycle in the colonic crypt provides a good example of how modeling can be used to find out key features of the system kinetics, and help to explain both the breakdown of homeostasis and the initiation of tumorigenesis. We use the cell population model by Johnston et al. to illustrate the power of mathematical modeling by considering two key questions about the cell population dynamics in the colonic crypt. We ask: how can a model describe both homeostasis and unregulated growth in tumorigenesis; and to which parameters in the system is the model most sensitive? In order to address these questions, we discuss what type of modeling approach is most appropriate in the crypt. We use the model to argue why tumorigenesis is observed to occur in stages with long lag phases between periods of rapid growth, and we identify the key parameters. PMID- 17873522 TI - Fbw7 and Usp28 regulate myc protein stability in response to DNA damage. AB - The cellular levels of the Myc oncoprotein are critical determinants of cell proliferation, cell growth and apoptosis and are tightly regulated by external growth factors. Levels of Myc oncoprotein also decline in response to intracellular stress signals such as DNA damage. We show here that this decline is in part due to proteasomal degradation and that it is mediated by the Fbw7 ubiquitin ligase. We have shown previously that the ubiquitin-specific protease Usp28, binds to the nucleoplasmic isoform of Fbw7, Fbw7alpha, and counteracts its function in mammalian cells. Usp28 dissociates from Fbw7alpha in response to UV irradiation, providing a mechanism how Fbw7-mediated degradation of Myc is enhanced upon DNA damage. Our data extend previous observations that link Myc function to the cellular response to DNA damage. PMID- 17873521 TI - Neural potential of a stem cell population in the hair follicle. AB - The bulge region of the hair follicle serves as a repository for epithelial stem cells that can regenerate the follicle in each hair growth cycle and contribute to epidermis regeneration upon injury. Here we describe a population of multipotential stem cells in the hair follicle bulge region; these cells can be identified by fluorescence in transgenic nestin-GFP mice. The morphological features of these cells suggest that they maintain close associations with each other and with the surrounding niche. Upon explantation, these cells can give rise to neurosphere-like structures in vitro. When these cells are permitted to differentiate, they produce several cell types, including cells with neuronal, astrocytic, oligodendrocytic, smooth muscle, adipocytic, and other phenotypes. Furthermore, upon implantation into the developing nervous system of chick, these cells generate neuronal cells in vivo. We used transcriptional profiling to assess the relationship between these cells and embryonic and postnatal neural stem cells and to compare them with other stem cell populations of the bulge. Our results show that nestin-expressing cells in the bulge region of the hair follicle have stem cell-like properties, are multipotent, and can effectively generate cells of neural lineage in vitro and in vivo. PMID- 17873524 TI - How arginine-rich domains coordinate mRNA maturation events. AB - Maturation of RNA is highly regulated from transcription to post-transcriptional processing and localization to specific cellular compartments. The complexes that contribute to these events are in many cases well understood; however, many of the protein factors that coordinate and regulate these RNA processing events remain poorly characterized. Among them are arginine-rich domains, most commonly sequences rich in arginine/serine (RS domains) or arginine/glycine/glycine (RGG boxes), that often appear among factors and complexes involved in RNA processing. They are emerging as key yet poorly understood players in the assembly and coupling of RNA processing events. PMID- 17873523 TI - Effects of hypoxia on heterotypic macrophage interactions. AB - The role of macrophages in modulating the systemic response to hypoxia and oxidative stress is emerging from basic biological processes, such as the regulation of red blood cell production, and from analysis of tumor progression, as a key factor determining whether cells survive, proliferate or differentiate under micro-environmental pressures. Our recent work identified a novel role for macrophages in promoting expansion of erythroid progenitors in vitro while confirming previous data that macrophages are not required for red cell enucleation. This work emerged from analyses of hypoxia and cell death in the Rb null fetal liver where we demonstrated that defects in erythropoietic islands were due to deterioration in the fetal liver microenvironment that disrupted heterotypic interactions of macrophages with erythroblasts and not to intrinsic defects in Rb null macrophages. The significance of these findings for the effect of hypoxia on macrophage interactions and activity during tumor progression is also discussed. PMID- 17873526 TI - Acute phosphate nephropathy following colonoscopy preparation. PMID- 17873527 TI - Mechanical ventilation management by pulmonologists and surgeons in patients with adult respiratory distress syndrome. AB - BACKGROUND: Treatment of patients with acute respiratory distress syndrome (ARDS) is complex, and management by a specialist with expertise in pulmonary mechanics may improve outcomes. We compared mechanical ventilation management of patients with ARDS by pulmonologists and surgeons. METHODS: We retrospectively reviewed 97 patients with an ICD-9 diagnosis of ARDS at 2 community hospitals. We collected information on demographics and all necessary parameters to calculate the acute physiology, age, and chronic health evaluation (APACHE II) score. Main outcomes included mortality and total days spent in the intensive care unit (ICU) and on mechanical ventilation. All outcomes were adjusted for APACHE II score using multiple logistic regression. RESULTS: Mechanical ventilation was managed by a pulmonologist in 62 patients and by a surgeon in 35 patients. Mortality rate was 35.5% (n = 22) in the patients treated by pulmonologists and 45.7% (n = 16) in patients treated by surgeons (P = 0.32). This result was unaffected by adjustment for APACHE II score. However, those surviving spent fewer days in the ICU (median of 10 vs 16 days; P = 0.07) and fewer days on mechanical ventilation (median of 7 vs 15 days; P = 0.003) when treated by pulmonologists. These results were unaffected by adjustment for APACHE II score. CONCLUSIONS: We found that patients who survived with ARDS spent fewer days on mechanical ventilation, and there was a trend for spending fewer days in the ICU when mechanical ventilation is managed by a pulmonologist compared with a surgeon. There was a lower mortality rate in the pulmonologist group, although this did not reach statistical significance. A small sample size and the retrospective design limit our findings. Further study using a multicenter design to determine if a disease specific specialist improves efficiency of care is needed because if our findings are confirmed, it would translate into significant cost savings. PMID- 17873528 TI - Comparison of clinical characteristics and prognosis in Taiwanese patients with coronary vasospastic angina pectoris without significant fixed coronary artery disease versus patients with significant fixed coronary artery disease and either stable angina pectoris or acute coronary syndromes. AB - BACKGROUND: Limited information is available comparing the clinical characteristics and prognosis for patients with coronary vasospastic angina in the absence of hemodynamically significant coronary artery disease (CAD) (defined as >50% stenosis) versus patients with significant fixed CAD presenting with either stable angina pectoris (SAP) or acute coronary syndromes (ACS). METHODS: Patients who underwent cardiac catheterization for suspected ischemic heart disease between August 1999 and February 2003 were followed clinically. For patients without hemodynamically significant CAD, a provocation test for coronary vasospasm was undertaken using a step-wise dose of intracoronary ergonovine administration. RESULTS: A total of 1134 patients were enrolled in the final analysis and stratified into 4 diagnostically distinct groups: control group (n = 239; mild CAD without coronary vasospasm); vasospasm group (n = 284; coronary vasospastic angina pectoris without hemodynamically significant CAD); SAP group (n = 110; hemodynamically significant CAD with SAP); ACS group (n = 501; hemodynamically significant CAD with ACS). Comparison of these 4 groups revealed that the ACS patients were more likely to be male, current smokers, and have hypercholesterolemia. In addition, this group had a significantly higher incidence of typical angina pectoris, 3-vessel CAD, and lower left ventricular ejection fraction. Between-group comparison revealed that vasospasm patients had a significantly higher incidence of early morning angina pectoris. Multivariate analysis showed that current smoking was the most independent risk factor associated with the diagnosis of coronary vasospastic angina pectoris in patients without hemodynamically significant CAD. During a median follow-up period of 49 months, recurrent angina pectoris was noted in patients from the control (n = 6; 3%), SAP (n = 9; 8%), vasospasm (n = 30, 11%), and ACS groups (n = 92; 18%); with nonfatal myocardial infarction identified during follow-up in the SAP (n = 5; 5%), vasospasm (n = 3; 1%), and ACS groups (n = 37; 7%). In addition, 29 and 3 cardiac deaths occurred in the ACS and SAP groups, respectively, whereas there were no such mortalities in the control and vasospasm groups. CONCLUSIONS: Early morning angina pectoris and cigarette smoking were the most common clinical characteristics in patients with coronary vasospasm. These patients had an excellent prognosis despite the possibility of recurrences of vasospastic angina pectoris. PMID- 17873529 TI - Sleep dysfunction in patients with GERD: erosive versus nonerosive reflux disease. AB - BACKGROUND: Sleep disturbance has been observed in patients with gastroesophageal reflux disease (GERD), but very few studies have further characterized sleep quality in patients with nonerosive esophageal reflux disease (NERD). This study was undertaken to investigate whether there are differences in sleep quality among patients with erosive esophagitis, NERD, and control subjects. METHODS: We performed symptom severity scoring and upper GI endoscopy in 20 healthy control subjects and 35 GERD patients, including 17 with NERD and 18 with erosive esophagitis. Sleep quality was measured by using Pittsburgh Sleep Quality Index (PSQI). RESULTS: Sleep disturbance was noted in 11 of 17 NERD patients and 12 of 18 patients with erosive esophagitis (P = NS) but none of healthy control subjects. The patient groups, erosive esophagitis and NERD, had greater PSQI scores compared with healthy control subjects (both P < 0.05). Both groups had similar median PSQI score (5.5 vs 6.0; NERD vs erosive esophagitis; P = NS). There was no significant correlation between reflux symptom severity score and PSQI score. CONCLUSIONS: Despite no difference in sleep quality between erosive esophagitis and NERD, NERD can have a significant impact on sleep comparable to erosive esophagitis. It is suggested that NERD should be treated aggressively and at least similarly to erosive esophagitis. PMID- 17873530 TI - Albendazole for the treatment of human echinococcosis: a review of comparative clinical trials. AB - BACKGROUND: Albendazole has been used in various ways in the treatment of cystic echinococcosis (CE). METHODS: We reviewed the available evidence regarding the role of albendazole for the treatment of patients with CE. The available comparative clinical trials (randomized or not) that examined the use of albendazole in CE were identified from the PubMed and the ISI Web of Science databases. Relevant data from the trials were extracted and evaluated. RESULTS: Thirteen studies were included in the review. Albendazole is superior to placebo for inoperable, symptomatic patients (1 study). In addition, in 4 trials that tested albendazole as a preoperative adjuvant therapy, the drug resulted in degeneration of hydatid cysts at the time of surgery in a considerable proportion of patients. Furthermore, combined therapy with albendazole and PAIR (Puncture, Aspiration, Injection of scolicidal agent, and Re-aspiration) technique was found more effective than albendazole or PAIR treatment alone, in a randomized controlled trial examining this issue. Finally, although existing evidence shows some superiority for albendazole compared to mebendazole, there is no definite proof about this. CONCLUSIONS: Although the available comparative trials provide considerable evidence for the role of albendazole in patients with CE, there are some important clinical questions that remained unanswered by the studies. One of them is whether the combination of albendazole with praziquantel is superior to albendazole alone when both effectiveness and drug toxicity are taken into account. Also, further studies should also compare the combination of albendazole/PAIR with albendazole/surgery focusing on both short and long term outcomes. PMID- 17873531 TI - Hepatitis A outbreak activity in the United States: responding to a vaccine preventable disease. AB - BACKGROUND: The occurrence of hepatitis A in the United States is heterogeneous because of disease cycles with substantial variation in incidence among states and involvement of numerous behavioral risk factors. In spite of the Advisory Committee on Immunization Practices' (ACIP) 1999 recommendation for routine hepatitis A immunization in states with high rates of disease and the fact that disease rates are at a historic low, outbreaks continue to occur. METHODS: We reviewed outbreaks of hepatitis A in the United States occurring from 1994 through 2004. We searched PubMed, ProMed, Google, and the CDC Foodborne Disease Outbreak and Epi-X Internet sites to ascertain the number and type of hepatitis A outbreaks. The CDC's MMWR publication and the Hepatitis Control Report were also searched. RESULTS: A total of 256 hepatitis A outbreaks were identified from 1994 through 2004. The mean number of outbreaks was 23 per year (median 25). The number of outbreaks in states with traditionally low/intermediate endemic rates of hepatitis A remained relatively constant during the study period. Outbreaks declined significantly (P = 0.01) in states with previously high rates of disease -most of which have implemented hepatitis A vaccination programs. CONCLUSIONS: Outbreaks of hepatitis A continue to occur in the United States despite the licensure of two safe and effective vaccines in 1995 and the apparent decline in the number of outbreaks in states with previously high rates of hepatitis A. The recent ACIP recommendation for universal hepatitis A vaccination at age 1 year in all states will contribute to a further reduction in hepatitis A outbreaks. PMID- 17873532 TI - A comparison of two proposed definitions for metabolic syndrome in the Chinese adult population. AB - BACKGROUND: The metabolic syndrome is a major risk factor for cardiovascular disease (CVD). We estimated the prevalence of the metabolic syndrome using the definitions proposed by the International Diabetes Federation (IDF) and the American Heart Association and the National Heart, Lung, and Blood Institute (revised ATP III), and compared the 2 definitions in the Chinese adult population. METHODS: We conducted a cross-sectional study among a nationally representative sample of 15,838 Chinese adults ages 35 to 74 years in 2000 to 2001. Waist girth, blood pressure, and blood levels of HDL-cholesterol, triglycerides, and glucose were measured according to standard methods. RESULTS: The overall age-standardized prevalence of the metabolic syndrome by the IDF and revised-ATP III definitions was 16.5% and 23.3%, respectively. The overall agreement of being classified as having or not having the metabolic syndrome was 93.2% for the 2 definitions, with a Kappa coefficient of 0.80. The prevalence significantly increased with age and was higher in women than in men by both definitions (23.3% vs 10.0% for IDF and 29.1% vs 17.7% for revised ATP III). Compared with men, women had a significantly higher prevalence of central obesity (37.6% vs 16.0%) and reduced HDL-cholesterol (46.5% vs 21.9%), whereas men had a significantly higher prevalence of raised blood pressure (44.2% vs 38.0%) compared with women. CONCLUSIONS: The metabolic syndrome is very common in China regardless of the definition used. Prevention and treatment of the metabolic syndrome should become a public health priority to reduce the CVD-related burden in China. PMID- 17873533 TI - Approach to patients with suspected hypersensitivity to local anesthetics. AB - Adverse reactions to local anesthetics are relatively common, but true IgE mediated hypersensitivity is extremely rare. Fortunately, the vast majority of adverse reactions occur via nonimmunologic means, but considerable confusion still exists among providers. We conducted a review of the literature to determine if earlier estimates of IgE-mediated allergy are consistent with current reports and whether current management strategies are consistent with these findings. We identified several confounding variables involved in the evaluation, including the roles of preservatives/additives, epinephrine, latex, and inadequate testing procedures. These problems may cause significant diagnostic challenges for clinicians. It is in fact much more likely that there is an alternate diagnosis, and in many cases clinicians can begin the evaluation in the office. When local anesthetic allergy is still suspected, the patient should be referred to an allergist for testing to determine if the suspected culprit drug can be safely used, or, if necessary, identify a suitable alternative. PMID- 17873534 TI - Oxidative stress and cardiac repair/remodeling following infarction. AB - Extensive cardiac remodeling after myocardial infarction (MI) contributes significantly to ventricular dysfunction. Factors regulating left ventricular remodeling at different stages after MI are under investigation. There is growing recognition and experimental evidence that oxidative stress mediated by reactive oxygen species plays a role in the pathogeneses of myocardial repair/remodeling in various cardiac diseases. After acute MI, oxidative stress is developed in both infarcted and noninfarcted myocardium. Accumulating evidence has demonstrated that oxidative stress participates in several aspects of cardiac repair/remodeling after infarction that include cardiomyocyte apoptosis, inflammatory/fibrogenic responses, and hypertrophy. The exact pathways on reactive oxygen species-mediated myocardial remodeling are under investigation. The therapeutic potential of oxidative stress-directed drugs in myocardial remodeling after infarction has not been fully realized. PMID- 17873535 TI - Dyskeratosis congenita associated with hypocellular myelodysplastic syndrome: a case report. AB - A 16-year-old female patient presented with complaints of malaise, dizziness, syncope, and nausea of 1-week duration. On dermatologic examination there were telangiectasias, atrophic areas, and poikiloderma with both hypopigmentation and hyperpigmentation on the neck and the proximal parts of the thighs. The bone marrow biopsy specimen showed hypocellularity and dysplastic megakaryocytic and erythroid elements, findings consistent with hypocellular myelodysplastic syndrome, which was further confirmed by cytogenetic studies. Thereafter, she was referred for allogeneic bone marrow transplantation. PMID- 17873536 TI - Late right ventricular perforation and hemothorax after transvenous defibrillator lead implantation. AB - A 53-year-old man with ischemic cardiomyopathy underwent prophylactic transvenous implantable cardioverter-defibrillator (ICD) placement. Nine days after the procedure, he had recurrent chest pain and left pleural effusion associated with a drop in hemoglobin. Hemothorax and right ventricular (RV) lead perforation were suspected on chest radiography and lead interrogation, and confirmed by thoracentesis and contrast computed tomography (CT) scanning, respectively. The CT-scan clearly demonstrated the RV lead tip projecting beyond the cardiac border into the anterior left pleural space. The perforated lead was removed in the operating room under transesophageal echocardiography guidance and a new transvenous lead was successfully placed a month later. This case highlights: 1) the importance of suspecting late RV perforation in patients with ICD implantation presenting with recurrent chest pain and/or pleural effusion; 2) the value of CT in its diagnosis; and 3) the need for a more careful management of this potentially life threatening complication. PMID- 17873537 TI - Group C streptococcal endocarditis. AB - Group C streptococcus is found in many domestic animals and rarely causes infection in human beings. Severe infections caused by these bacteria are associated with high morbidity and mortality rates. We present a case of group C streptococcus endocarditis with sequelae, right-eye endophthalmitis, and multilobar pneumonia caused by septic embolization from the infected mitral valve. PMID- 17873538 TI - Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome: suspected association with titanium bioprosthesis. AB - Drug rash with eosinophilia and systemic symptoms (DRESS), also known as hypersensitivity syndrome, is an idiosyncratic drug reaction presenting with fever, diffuse lymphadenopathy, exfoliative dermatitis, and visceral involvement, which may include hepatitis, pneumonitis, pericarditis, myocarditis, nephritis, and colitis. This report describes a 19-year-old, previously healthy man with manifestations of hypersensitivity (DRESS) syndrome after acquiring a titanium bioprosthesis for a spinal fracture. To our knowledge, there have been no prior reports of DRESS syndrome in association with titanium bioprosthetic implants. PMID- 17873539 TI - Gastrointestinal amyloidosis associated with transthyretin Phe64Ser mutation. AB - Familial amyloidotic polyneuropathy (FAP) is a hereditary generalized amyloidosis that results from mutations in the transthyretin (TTR) gene. More then 100 mutations of TTR have been described. Corresponding to the wide variety of TTR mutations, FAP presents with diverse clinical phenotypes. TTR-Phe64Ser is a rare mutation that has previously only been described once in a Canadian family that presented with oculoleptomeningeal symptoms. We report the clinical and molecular characterization of the first described case of a TTR-Phe64Ser mutation in an African-American family with profound gastrointestinal symptoms. PMID- 17873540 TI - Postpartum reversible cerebral vasoconstriction syndrome. AB - Postpartum reversible cerebral vasoconstriction syndrome, also known as postpartum cerebral angiopathy, is clinically characterized by headache and focal neurologic deficits, and angiographically by transient, fully reversible cerebral vasoconstriction. A 26-year-old woman was brought to the emergency room with a 3 day history of confusion, agitation, and headache. She was 2 weeks postpartum. She went on to develop right leg weakness two days after admission. A cerebral angiogram showed diffuse irregularities of all intracerebral vessels, and MRI showed multiple acute infarcts. Her clinical condition improved significantly over the next several days without any intervention, and she was discharged. MRA 3 months after initial presentation was normal. It is important to consider this syndrome in the differential diagnosis in patients presenting with headache and focal neurologic deficits in the postpartum period. PMID- 17873541 TI - Glucagonoma syndrome: survival 21 years with concurrent liver metastases. AB - A patient who survived for 21 years since initial discovery of glucagonoma with concurrent liver metastases is described. Psychiatric symptoms, weight loss, necrolytic migratory erythema, diarrhea, and diabetes mellitus developed gradually after diagnosis of the tumor. No specific treatment was administered. The longevity of this patient may be related to the slow tumor growth expressed histologically by ischemic necrosis of the malignant cells and in imaging by extensive tumor calcifications, a very rare finding in this type of the tumor. PMID- 17873542 TI - Hepatocellular carcinoma in a noncirrhotic patient with hereditary hemochromatosis. AB - We report the case of a 66-year-old man with genetic hemochromatosis who was found to have hepatocellular carcinoma (HCC) in the absence of cirrhosis. This is a rare and life-threatening complication of noncirrhotic hemochromatosis that has been described only 10 times in the English literature. In addition to presenting our case, we also cite some other potential causes of HCC in noncirrhotic patients that should be clinically considered. Although the incidence of HCC in noncirrhotic hemochromatosis patients is not sufficiently high to warrant routine screening, physicians should be aware that this fatal complication may rarely occur. PMID- 17873543 TI - Gastrointestinal involvement in a case of hereditary angioedema: could the early weaning have had a role? AB - Hereditary angioedema (HAE) is a noninflammatory disorder due to reduced C1 inhibitor level and/or function and characterized by recurrent, circumscribed, and self-limiting episodes of cutaneous and mucous membrane swellings involving different organs. A heterogeneous group of mutations in the C1-inhibitor gene have been found. HAE might present with diverse clinical pictures, even within families with the same mutation, but the cause of this variability is not known yet. We describe the case of type II HAE in a young adult presenting with recurrent abdominal pain for many years, occasionally associated with ascites. We suppose that an early weaning might have influenced his phenotype, making his gastrointestinal tract a "vulnerable organ," in which hereditary angioedema could express itself. PMID- 17873544 TI - Predicting outcomes in the orthotic management of painful, idiopathic pes cavus. AB - OBJECTIVE: People who have extremely high arched feet are subject to substantial foot pain, despite a lack of obvious pathology. Customized foot orthoses improve pain and function and reduce foot pressure, but their specificity is unclear. This study sought to identify predictive variables for improvement and to determine whether changes in foot pressure were correlated to changes in pain and function. DESIGN: Retrospective analysis of data from a randomized controlled clinical trial. SETTING: Clinical movement analysis laboratory, School of Physiotherapy, University of Sydney. PARTICIPANTS: Subjects with painful, idiopathic pes cavus. INTERVENTIONS: Sixty-six subjects received customized foot orthoses; sixty-seven subjects were allocated a sham intervention. MAIN OUTCOME MEASURES: Foot pressure data, location and intensity of pain, Foot Posture Index values, and anthropometric and quality of life variables. RESULTS: No relationship between change in foot pressure and change in symptoms was found in either group. No individual characteristics were linked to improvement. Subjects who improved most had substantial pain, lowest function scores, and lowest scores for quality of life variables at entry. There was a possible link, in the orthosis group, between improvement and pain confined to the rear-foot region. CONCLUSIONS: The mechanisms by which orthotic intervention is effective in improving pain and function in painful, idiopathic pes cavus remain unclear and equivocal. A strong placebo effect may be in place, or perhaps relatively small changes in foot pressure, even those brought about by a flexible insole with limited shock-absorbing properties, is enough to achieve a clinically meaningful change in symptoms. PMID- 17873545 TI - The effects of external ankle support on dynamic restraint characteristics of the ankle in volleyball players. AB - OBJECTIVE: To examine any changes in electromechanical delay and reaction time as a result of the use of external ankle supports over an entire season (3-5 months) in college volleyball players. DESIGN: A 2 x 3 pre-post factorial design. SETTING: Biomechanics laboratory, Human Performance Research Center. PARTICIPANTS: Thirty healthy, active male and female intercollegiate volleyball players were recruited for this study (age, 20.4 +/- 2.3 years; height, 183.1 +/- 8.6 cm; weight, 74.0 +/- 9.5 kg). INTERVENTIONS: External supports consisted of the subjects wearing either tape or braces for practices and games for the duration of the volleyball season. Subjects in the control group wore nothing on their ankles for practices and games for the duration of the volleyball season. MAIN OUTCOME MEASURES: The electromechanical delay (EMD) of the peroneus longus was determined by the onset of force contribution after artificial activation, as measured by electromyographic (EMG) and forceplate data. Reaction time was measured after an inversion perturbation during walking. RESULTS: No significant (F2,27 = 0.141, P = 0.869) interaction was observed for reaction time between the groups over time. No significant (F2,27 = 0.236, P = 0.791) interaction was observed for EMD between groups over time. CONCLUSION: Use of an external ankle support over an entire season does not induce neuromuscular changes in the onset timing of the peroneus longus. PMID- 17873546 TI - The development and validation of a quality of life-measurement tool for patients with meniscal pathology: the Western Ontario Meniscal Evaluation Tool (WOMET). AB - OBJECTIVE: To develop and validate a disease-specific, health-related quality of life (HRQOL) index for patients with meniscal pathology. Our hypothesis was that the Western Ontario Meniscal Evaluation Tool (WOMET) would provide adequate reliability, validity, and responsiveness in measuring HRQOL in patients with meniscal tears or who have undergone meniscal repair or resection. STUDY DESIGN: Validation of a measurement tool. SETTING: A tertiary, university-affiliated, sport medicine clinic. PARTICIPANTS: A methodological protocol based on that of Guyatt et al was used to develop the Western Ontario Meniscal Evaluation Tool (WOMET). Patients with meniscal symptomology and in whom magnetic resonance imaging had suggested meniscal pathology were selected from referrals to a sport medicine clinic. Using this cohort, the development of the WOMET proceeded through item generation, reduction, and instrument pretesting. A second cohort of postarthroscopy patients with confirmed meniscal pathology was used to assess the reliability of the WOMET and validate the instrument. RESULTS: The final instrument has 16 items representing the domains of physical symptoms (nine items), sports/recreation/work/lifestyle (four items), and emotions (three items). It demonstrated adequate content and construct validity when compared with other measures. Test-retest reliability was assessed and was found to be high, with an intraclass correlation coefficient of 0.833. The new instrument was also found to be more responsive than other knee measurement tools when assessed in the same cohort. CONCLUSIONS AND CLINICAL RELEVANCE: The WOMET is a disease specific tool designed to evaluate HRQOL in patients with meniscal pathology. It is therefore put forth as a validated measurement tool to be used in clinical trials evaluating treatments for meniscal pathology. It could also be used as a prospective outcome measure in research or in clinical practice. PMID- 17873547 TI - Bilateral asymmetries in clinical measures of lower-extremity anatomic characteristics. AB - OBJECTIVE: To quantify side-to-side differences in lower-extremity anatomic characteristics, and to compare the magnitude of left-right differences with the measurement error for each variable. DESIGN: : Descriptive. SETTING: Applied neuromechanics research laboratory. PARTICIPANTS: One hundred healthy participants (50 male, 50 females). ASSESSMENT OF RISK FACTORS: One examiner measured 14 anatomic characteristics on the left and right lower extremities. The value on the left was subtracted from value on the right, and 68% (+/-1 SD) and 95% (+/-1.96 SD) confidence intervals were constructed around the mean differences, respectively. These values were compared with the examiner's absolute measurement error for each measure. MAIN OUTCOME MEASUREMENTS: Total leg length, pelvic angle, hip anteversion, standing and supine quadriceps angle, tibiofemoral angle, knee laxity, genu recurvatum, femur and tibia length, tibial torsion, rearfoot angle, and navicular drop. RESULTS: Left-right differences in pelvic angle, tibial torsion, and navicular drop exceeded the measurement error in more than 32% of the cases. Five to thirty-two percent of the cases had left right differences exceeding the measurement error for hip anteversion, standing and supine quadriceps angle, tibiofemoral angle, knee laxity, genu recurvatum, and femur length. Asymmetries in limb length were not observed. CONCLUSIONS: Bilateral asymmetries exist in many clinical alignment characteristics, indicating that measurements taken on one limb may not be representative of the contralateral limb. We recommend measuring both extremities when anatomic characteristics are included as part of preseason screenings and prospective study designs to ensure valid comparison. PMID- 17873548 TI - Validation of a noninvasive maturity estimate relative to skeletal age in youth football players. AB - OBJECTIVE: To validate a non-invasive measure of biological maturity (percentage of predicted mature height at a given age) with an established indicator of maturity [skeletal age (SA)] in youth American football players. DESIGN: Cross sectional. SETTING: Two communities in central Michigan. PARTICIPANTS: 143 youth football players 9.27 to 14.24 years. METHODS: Height and weight were measured, and hand-wrist radiographs were taken. SA assessed with the Fels method was the criterion measure of maturity status. Chronological age (CA), height, and weight of the player and midparent height were used to predict mature height; current height of the player was expressed as a percentage of his predicted mature height as a noninvasive estimate of biological maturity status. MAIN OUTCOME MEASURE: Boys' maturation was classified as late, on time, or early maturing on the basis of the difference between SA and CA and of present height expressed as a percentage of predicted mature height. Kappa coefficients and Spearman rank-order correlations were calculated. Characteristics of players concordant and discordant for maturity classification with SA and percentage of predicted mature height were compared with MANCOVA. RESULTS: Concordance between methods of maturity classification was 62%. The Kappa coefficient, 0.46 (95% CI 0.19 to 0.59) and Spearman rank-order correlation, rs = 0.52 (P < 0.001) were moderate. Players discordant for maturity status varied in midparent height and percentage of predicted mature height, but not in predicted mature height. CONCLUSION: Percentage of predicted mature height is a reasonably valid estimate of biological maturity status in this sample of youth football players. PMID- 17873549 TI - Prolonged neuropsychological impairments following a first concussion in female university soccer athletes. AB - OBJECTIVE: Although research is accumulating on the cognitive sequelae from sports-related concussions in men, little to nothing is known about the prolonged cognitive outcome after a concussion in women. This point is important because recent evidence suggests that female athletes are at greater risk of sustaining a concussion. DESIGN: We assessed cognitive functioning after a first concussion in female soccer players, 6 to 8 months after their injury. The first-time concussed athletes were compared with a group of age-matched teammates who had never experienced a concussion. SETTING AND PARTICIPANTS: A total of 22 female university-level soccer players participated in the study. MAIN OUTCOME MEASUREMENTS: Paper-and-pencil and computerized tasks were used to assess different neuropsychological functions. RESULTS: Short- and long-term verbal memory, attention, and simple reaction time were normal. In contrast, compared with the control group, the concussed athletes were significantly slower on tasks that required decision making (complex reaction time), inhibition and flexibility (Stroop), and planning (Tour of London task). CONCLUSIONS: The results of this study suggest that cognitive functions related to cognitive processing speed are most vulnerable to a sports-related concussion and are still impaired for a half year after injury in university-level female soccer players. PMID- 17873550 TI - Physical exercise-associated gene expression signatures in peripheral blood. AB - OBJECTIVE: To assess response to physical stress, gene expression profiles in peripheral blood cells were analyzed using an original microarray carrying 1467 stress-responsive complementary DNA probes. DESIGN: Gene expression was analyzed at 4, 24, and 48 hours after exercising on a cycle ergometer at 60% VO2 max for 1 hour (aerobic exercise) or until exhausted (exhaustive exercise). SETTING: Institute of Health Biosciences, University of Tokushima Graduate School. PARTICIPANTS: Twelve healthy male students of the postgraduate or undergraduate school. INTERVENTIONS: The volunteers performed the aerobic or exhaustive exercise on a cycle ergometer. MAIN OUTCOME MEASUREMENTS: Detection of aerobic exercise-responsive or exhaustive exercise-responsive genes in peripheral blood cells. RESULTS: Aerobic and exhaustive exercise transiently changed the expression of 21 and 16 genes, respectively, with the peak at 4 hours. Only 2 genes significantly responded to both types of exercise. Exhaustive but not aerobic exercise produced a secondary response with significantly altered expression of 14 genes at 24 hours. Five of those genes encode receptors for neurotransmitters (HTR1A, CHRNB2, GABRB3, GABRG3, and LOC51289). CONCLUSIONS: The behavior of the individual genes shown here may be informative to objectively assess acute physical stress and exhaustion-associated responses. PMID- 17873551 TI - Low-intensity exercise improves quality of life in patients with Crohn's disease. AB - OBJECTIVE: This study examines the effects of a low-intensity walking program on the quality of life in patients with Crohn's disease. DESIGN: Patients were randomized into exercise and nonexercise groups for a prospective study. SETTING: Patients were recruited at the inflammatory bowel disease outpatient clinic at the London Health Science Center, London, Ontario. PATIENTS: Thirty-two adult patients met the inclusion criteria of (1) mildly active disease or disease in remission, (2) habitual physical activity of less than 2 times per week of vigorous activity, (3) not anticipating change of dose or type of medication for Crohn's disease, and (4) no history of cardiovascular disease. All 32 patients who entered the study completed the 3-month study. INTERVENTION: Patients performed low-intensity walking at an interval of 3 times per week for a duration of 3 months. Each walking session lasted for 30 minutes. MAIN OUTCOME MEASUREMENTS: The Inflammatory Bowel Disease Questionnaire, the Inflammatory Bowel Disease Stress Index, and the Harvey-Bradshaw Simple Index were used as outcome. Survey measurements were recorded at 1-month intervals on commencement of the walking program. RESULTS: Patients in the exercise group experienced a statistically significant (P < 0.05) improvement in quality of life in all 3 of the outcome measurement questionnaires with no detrimental effects in terms of disease activity. CONCLUSION: A low-intensity walking program may have a beneficial effect in patients with Crohn's disease and improve their quality of life with no exacerbations in disease symptoms. PMID- 17873552 TI - Trampolines at home and playgrounds: a joint statement with the Canadian paediatric society. PMID- 17873553 TI - Practical management: community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA): the latest sports epidemic. AB - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has gained international recognition as a superbug that causes serious infectious outbreaks in high-risk populations such as athletes. Clusters of cases in various athletic teams, particularly contact sports, have been reported since 1993 in the United States and more recently in Canada. CA-MRSA infections are not limited to North America, and all athletes are considered high risk. Skin-to-skin contact appears to be the primary mode of transmission. While typical infections are local skin and soft-tissue abscesses, CA-MRSA infections can spread systemically and lead to significant morbidity and mortality if not promptly identified and treated. The gold standard of treatment for all abscesses is incision and drainage with wound culture for bacterial identification and antibiotic sensitivity testing. A limited number of antibiotics are currently useful in the treatment of CA-MRSA and are reviewed. Geographical variation in patterns of antibiotic resistance further complicates the treatment. Meticulous, consistent use of infection prevention strategies is critical to control outbreaks in the athletic population. Good hygiene, prompt identification of infection, limited exposure to infected persons and contaminated objects, and proper treatment combined with close follow-up of infected athletes will help contain CA-MRSA outbreaks. Future research is needed to explore person-to-person and fomite transmission risks, to define the significance of nasal carriage and skin colonization in relation to CA-MRSA infections, and to further investigate antibiotic resistance patterns. Universal education is needed for all athletes and personnel who provide care in the athletic setting to help control this widespread epidemic. PMID- 17873554 TI - Open tension-free hernia repair in soccer players: preservation or primary neurectomy of the ilioinguinal nerve? PMID- 17873555 TI - Chronic lateral knee pain in a cyclist: popliteal artery entrapment. PMID- 17873556 TI - Recalcitrant knee pain in a recreational runner. PMID- 17873557 TI - "Ciprofloxacin-induced" bilateral rectus femoris tendon rupture. PMID- 17873558 TI - Lateral humeral epicondyle fracture secondary to avulsion of the anconeus muscle. PMID- 17873559 TI - Prevention of obesity in young children through physical activity. PMID- 17873560 TI - Prognosis for lower extremity injuries in marathon runners. PMID- 17873561 TI - Arthroscopic or open repairs for recurrent anterior shoulder instability: a review. PMID- 17873562 TI - Detection of postconcussion abnormalities after injury in young athletes. PMID- 17873563 TI - Heart failure. Foreword. PMID- 17873564 TI - Heart failure with preserved systolic function: giving well-deserved attention to the "other" heart failure. AB - Heart failure with preserved systolic function is common in patients hospitalized with decompensated heart failure and is associated with postdischarge morbidity and costs similar to patients with heart failure and systolic dysfunction. It is common in the older people, and hypertension and cardiac ischemia are often etiological factors. Nurses must be able to recognize left ventricular diastolic abnormalities and understand treatment priorities and treatment options on the basis of structural cardiovascular disease; etiology and risk factors; and signs, symptoms, and hemodynamic parameters. Currently, clinical treatments are on the basis of individual randomized clinical trials; however, there are general principles that should be followed during hospitalization and as part of general practice. As in the treatment of systolic heart failure, nurses have active roles in ensuring accurate assessment; optimal care planning; implementation of clinical, psychosocial; and education interventions; and timely and accurate evaluation so that patients have the best chance for successful hospital and postdischarge outcomes. PMID- 17873566 TI - Pharmacological treatment of heart failure. AB - This article provides an overview of heart failure (HF) and pharmacological treatment of systolic left ventricular dysfunction. The purpose of this article is to provide nurses the knowledge of current treatment recommendations and the Five Million Lives campaign sponsored by the National Institute of Healthcare Improvement. This initiative is a national campaign to protect 5 million patients from medical harm by promoting evidence-based standards of practice to improve the healthcare of Americans. HF has become part of this national initiative and the National Institute of Healthcare Improvement in conjunction with the American College of Cardiology/American Heart Association has implemented guidelines to improve the care of HF patients. Nurses would be expected to be familiar with these guidelines, as regulatory agencies will be using these guidelines as a benchmark to evaluate the quality of care provided to patients with this diagnosis. PMID- 17873567 TI - Management strategies to meet the core heart failure measures for acute decompensated heart failure: a nursing perspective. AB - Despite enormous advances in the medical management of heart disease, heart failure (HF) persists as a leading cause of hospitalization in our elderly. In 2001, the American Heart Association and the American College of Cardiology published Guidelines for Secondary Prevention for Patients With Coronary and Other Atherosclerotic Vascular Disease. The guidelines proactively responded to a growing body of evidence confirming that comprehensive risk factor management and risk reduction improve quality of life and survival, while reducing recurrent cardiovascular events. In spite of the well-crafted, comprehensive HF guidelines, morbidity, mortality, and hospital readmission rates for acute decompensated heart failure remain high, and adherence to HF guidelines is not always optimal. The Joint Commission has implemented a number of quality care performance indicators based on the Guidelines for Secondary Prevention; among them are the Core HF Measures for hospitalized HF patients. The Core HF Measures are endorsed by the Center for Medicare and Medicaid and has been adopted as a national benchmark for measurement and public reporting of healthcare performance and for Medicare payments (Joint Commission). The implementation and monitoring of Core HF Measures has prioritized attention toward patient education and risk factor modification to prevent future hospitalization. Critical care nurses are on the frontline to champion uptake and adherence of Core HF Measures. The purpose of this article is to highlight the critical component that nursing care, guided by the Core HF Measures, can offer to improve the quality of patient care in acute decompensated heart failure. PMID- 17873568 TI - Proactive monitoring: implications of implantable devices for future heart failure management. AB - Heart failure (HF) decompensation continues to account for approximately 1 million hospitalizations per year in the United States. Pulmonary congestion is the hallmark sign of worsening HF. Better strategies aimed at identifying subclinical congestion would be of great value in the management of HF. Implantable hemodynamic and/or thoracic impedance monitoring systems, both currently available and under investigation, can detect pulmonary congestion before traditional signs and symptoms occur. These implantable monitors can provide valuable information of ongoing fluid status. Data retrieval can be useful for monitoring effectiveness of treatment and patient teaching, thereby resulting in an individualized treatment regimen based on real-time data. Proactive monitoring of HF patients may prevent future HF decompensation. PMID- 17873569 TI - Peripheral ultrafiltration for patients with volume overload: a center's 4-year experience. AB - The overall prevalence of heart failure in the United States is thought to be over 5 million people, with an additional 550 000 cases diagnosed each year. Peripheral ultrafiltration provides an additional method for relieving congestion in patients with decompensated heart failure who are resistant to diuretics. A competency-based education program for staff ensures adequate knowledge to safely care for the patient. Over a 4-year period, 120 patients have been treated for volume overload using peripheral ultrafiltration at Sharp Memorial Hospital. PMID- 17873570 TI - The next treatment option: using ventricular assist devices for heart failure. AB - Ventricular assist devices (VADs) are becoming more commonplace in the hospital and community settings as the number of patients living with heart failure increases. Patients being discharged after hospitalization for heart failure rose from 399 000 in 1979 to 1 099 000 in 2004, an increase of 175%. Patients with heart failure become severely debilitated finding activities of daily living including eating, bathing, and walking a great effort. Patients with end-stage heart failure are often sent home on inotropic therapies and referred to hospice care. The use of VADs for these patients can dramatically improve both the quality and the length of life. VADs can be broadly categorized as being either continuous flow (fluid dynamic) or pulsatile (volume displacement) and either can be used as short- or long-term support devices. The critical care nurse is in a unique position to educate patients with chronic heart failure on options available to improve their quality of life including VAD therapy. VADs are available for destination therapy for those not meeting transplant criteria, offering a longer quality of life. As centers gain more experience and referrals are made earlier in the disease process, VAD patient care will be more streamlined decreasing length of stay. PMID- 17873571 TI - Evaluation and treatment of fever in intensive care unit patients. AB - Fever is a common complaint in hospitalized patients, with estimates that more than 30% of ward patients and as much as 90% of critically ill patients will experience fever. Much of the treatment of fever, however, is based on tradition and the belief the fever is harmful to the patient rather than on scientific evidence. There is a need to determine via analysis of the literature the best evidence-based approach to the identification and treatment of fever with attention to appropriate measurement of body temperature, diagnostic evaluation, changing of indwelling catheters, administration of antipyretics, and alteration in antimicrobial therapy. The advanced practice nurse is uniquely capable of gathering this evidence and implementing a plan of care that meets the individual needs of the patient, family, nursing staff, and healthcare system. PMID- 17873572 TI - The introduction of family presence evidence-based practice into a baccalaureate nursing curriculum. AB - The topic of family presence (FP) during cardiopulmonary resuscitation or invasive procedures has recently received attention and debate among healthcare professionals due to pioneering research in this field. Studies completed have included family perspectives on family presence, patients' feelings on family presence, and healthcare providers' views on family presence. Two key areas found to correlate with family presence acceptance among healthcare providers are education and experience. Senior nursing students in one baccalaureate program were introduced to this topic during a 3-hour class on death and dying. Comparisons between pretest and posttest scores revealed an increase in the acceptance of family presence as a priority in nursing care of the critically ill. PMID- 17873574 TI - Neuroimmune interactions in allergic skin diseases. AB - PURPOSE OF REVIEW: Recent studies have advanced our understanding that allergic inflammation triggers neuronal dysfunction, thereby modulating inflammation related changes in affected tissues including the skin. Vice versa, evidence has emerged that inflammatory responses are controlled by neurons. Moreover, structural cells and invading immune cells express neuronal receptors and release mediators which directly communicate with nerve endings in the skin. RECENT FINDINGS: During the allergic response, skin cells do not only represent a significant source of neuromediators but also represent targets for neuropeptides or neurotrophins as well as neurotransmitters in the inflamed tissue. During the last decade, it has become obvious that a large variety of molecules influence the adaptive as well as the innate immune response. Beside neuropeptide receptors, proteinase-activated receptors, novel histamine receptors, different cytokine or chemokine receptors play a role in the pathophysiology of atopic and allergic diseases. SUMMARY: Peripheral sensory and autonomic nerves are critically involved in many pathways of the innate and adoptive immune system during allergic and atopic skin diseases. Further dissection of receptor-mediated and intracellular signal pathways will help to develop more effective therapeutic approaches for allergic and inflammatory skin diseases. PMID- 17873575 TI - Interleukin-17 in inflammatory skin disorders. AB - PURPOSE OF REVIEW: Recently, a novel and unique subset of interleukin (IL)-17 producing CD4+ T helper (Th17) cells, distinct from Th1 and Th2 cells, was discovered. The question is addressed as to what extent inflammatory skin diseases are associated with the actions of this newly discovered Th17 cell subset. RECENT FINDINGS: Th17 cells are involved in protection against bacterial pathogens. In addition, it is now clear that Th17 cells may also be crucial in the pathogenesis of various chronic inflammatory diseases that were formerly categorized as Th1-mediated disorders. SUMMARY: In this review, we summarize the current knowledge of IL-17 and Th17 cells and discuss the possible role of IL-17 in the pathology of psoriasis, contact hypersensitivity and atopic dermatitis. Whereas IL-17 may play an important role in the pathogenesis of psoriasis and contact hypersensitivity, its role in atopic dermatitis is still unclear. PMID- 17873576 TI - Molecular basis of atopic dermatitis. AB - PURPOSE OF REVIEW: Atopic dermatitis is a common chronic inflammatory skin disease and there are numerous publications on this topic. This review will focus on developments in understanding the molecular basis of atopic dermatitis while considering the genetic background, skin barrier impairment, immune system deviation and microbial superinfections. RECENT FINDINGS: Atopic dermatitis is a complex genetic disease in which gene-gene and gene-environment interactions play a key role. Surprisingly some genetic regions of interest were found to be overlapping with loci identified to play a role in another very common inflammatory skin disease, psoriasis, while no overlap has so far been observed with asthma. Impairment of the skin barrier followed by antigens trespassing seems to play an important role, favouring sensitization via transepidermal penetration which is the focus of current investigations. Superinfections by pathogens such as Staphylococcus aureus due to a weak innate defence seem to be significant in atopic dermatitis as they elicit a strong inflammatory response. SUMMARY: Atopic dermatitis is a chronic inflammatory skin disease with a high incidence in school children and adults. Disease pathogenesis is complex and the background is multifactorial, making the underlying predispositions elusive. Understanding new pathogenic pathways may lead to the development of new drugs with enhanced benefit for the patient. PMID- 17873577 TI - Mastocytosis and allergy. AB - PURPOSE OF REVIEW: To illustrate features of allergy in mastocytosis. RECENT FINDINGS: The rates of atopy in patients with mastocytosis have generally been found to be similar to those of the normal population, although the incidence of anaphylaxis is much higher in mastocytosis. Introduction of objective pathologic criteria by the WHO for the diagnosis of mastocytosis has greatly facilitated the workup of patients with suspected mastocytosis, and has led to identification of mast cell disease in a subset of patients with anaphylaxis. There is increasing evidence that an activating c-kit mutation (D816V) exists in a subset of patients with recurrent mast cell activation symptoms who have normal-appearing bone marrow biopsies in routine evaluations without skin lesions. The genetic deficiency of alpha tryptase has not been found to influence serum tryptase levels in patients with mastocytosis. SUMMARY: Pathologic mast cell activation is a key finding in both allergic diseases and mastocytosis, albeit caused by entirely different mechanisms. Mastocytosis should be suspected in patients with recurrent anaphylaxis, who present with syncopal or near-syncopal episodes without associated hives or angioedema. PMID- 17873578 TI - Hypersensitivity reactions to biological agents with special emphasis on tumor necrosis factor-alpha antagonists. AB - PURPOSE OF REVIEW: Several biological agents have been introduced into the drug market and more are emerging. Adverse reactions to these agents have recently been classified into five different subtypes. Some of these reactions are frequent but without consequences for the patients. Others are less frequent but potentially life-threatening, and they include allergic reactions. RECENT FINDINGS: Hypersensitivity reactions are well described adverse drug reactions, corresponding to the ss-type of the newly proposed classification of adverse reactions induced by biological agents. We focus our search on tumor necrosis factor-alpha antagonists, as they represent a dramatic improvement in the therapy of both rheumatic and inflammatory bowel diseases and because adverse reactions have been closely scrutinized. We also add cases from our own experience. We found very few properly documented allergic reactions. SUMMARY: Hypersensitivity reactions to tumor necrosis factor-alpha antagonists are not rare. Whether these manifestations have to be considered type beta or type gamma reactions is still a matter of debate. There is a need for allergological tests in vivo and in vitro. PMID- 17873579 TI - New aspects of the molecular basis of contact allergy. AB - PURPOSE OF REVIEW: The aim of the review is to provide an up-to-date scenario of the mechanisms governing contact allergy, a widely diffused immune response to small chemicals (haptens) penetrating the skin. RECENT FINDINGS: The availability of animal models for contact allergy, such as murine contact hypersensitivity, is of great importance in understanding the pathomechanisms of the allergic response, although all these findings need confirmation in humans. Contact allergy is the result of the activation of both innate and adaptive immunity in response to haptens. Both skin resident cells, such as keratinocytes and mast cells, and immigrating leucocytes, including T lymphocytes and natural killer cells, actively participate in the reaction. Different types of T-regulatory cells appear to be crucial in the prevention of contact allergy or in the early termination of the reaction. Understanding the mechanisms that regulate immune responses to haptens is critical for the development of innovative therapeutic approaches. SUMMARY: Although contact allergy is predominantly a T-cell-mediated disease, humoral immune responses and innate immunity actively participate in the initiation and expression of the allergic disease. PMID- 17873580 TI - 'New' contact allergens. AB - PURPOSE OF REVIEW: Due to the continuously changing environmental conditions, it is necessary to regularly monitor and update the spectrum of contact allergens that elicit contact dermatitis. New contact allergens and known contact allergens with currently increasing importance need to be identified for diagnostic and preventive purposes. RECENT FINDINGS: Within the last few years, allergic contact allergy to a number of substances derived from plants and other materials was reported for the first time. Furthermore, it has become obvious that dyes, especially paraphenylenediamine-related dyes, and fragrances are sources of contact allergens with increasing frequency. It is likely that within these groups of substances some as yet unidentified agents are relevant allergens. SUMMARY: It is an ongoing challenge for clinicians to meticulously explore the exposure of eczema patients to possible new allergens. Dyes and fragrances, in particular, are of increasing significance not only because of their known ingredients but also because of new allergenic compounds. PMID- 17873581 TI - The role of human beta defensins and cathelicidins in atopic dermatitis. AB - PURPOSE OF REVIEW: Atopic dermatitis is a chronic inflammatory skin disease associated with significant barrier disruption, T-helper type 2 mediated skin inflammation, and an impaired innate immune response. These characteristics increase the susceptibility of atopic dermatitis patients to recurrent skin infections, some of which may have potentially fatal implications. The mechanisms resulting in this increased propensity for skin infections have been an area of active investigation. RECENT FINDINGS: Antimicrobial peptides are an integral component of the innate immune response due to their broad spectrum activity against invading pathogens. Recent studies have shown that these peptides are effective at killing Staphylococcus aureus, herpes simplex virus, vaccinia virus, and the Malassezia species, pathogens associated with significant morbidity in patients with atopic dermatitis. Additionally, these peptides are deficient in the skin of atopic dermatitis patients, suggesting that the increased propensity of patients towards skin infection is due to the lack of antimicrobial peptide expression. SUMMARY: The current review will examine recent literature on the role of antimicrobial peptides in atopic dermatitis in an effort to improve our understanding of why patients with the condition suffer from recurrent infections. PMID- 17873582 TI - Chirality in ocular agents. AB - PURPOSE OF REVIEW: To review the role of chirality in current ocular pharmacology. The importance of stereo-isomeric purity has frequently been emphasized in recent years. Development of chirally pure medications can lead to improved efficacy and side-effect profiles. Practitioners prescribing ocular agents may benefit from understanding the effects of chirality in their evaluation of old and new medications. RECENT FINDINGS: Chirality can affect multiple classes of ocular agents. Although the ways in which stereo-isomers influence the properties of a drug differ, this review illustrates the benefit of knowledge of individual isomers' effects in clinical decision making. The variety of possible effects stereo-isomers produce further underlines the importance of purification and in-depth analysis of chiral compounds. SUMMARY: Many important agents exist as a mixture of two different stereoisomers. Both isomers may produce a pharmacological effect; however, these effects may be different from one another and one isomer may even give a result opposite from the desired pharmacological effect. Here we examine published findings on ocular medications relating to their chiral nature and summarize the possible ways chirality affects the activity of a few ocular agents. Many more ocular medications have not been investigated to ascertain their chiral properties. This review adds to the recent emphasis on investigating stereo-isomers for individual selectivity of beneficial and adverse profiles. PMID- 17873583 TI - Classification of ocular allergy. AB - PURPOSE OF REVIEW: The purpose of this article is to summarize the clinical presentations associated with the classification of ocular allergy. This article also serves to summarize recent findings of pathophysiological mechanisms associated with ocular allergy and to highlight recently improved diagnostic methods for ocular allergic inflammation. RECENT FINDINGS: The term allergic conjunctivitis may not sufficiently describe all forms of allergic eye disease, thus a new classification system is desirable, preferably derived from the varied pathophysiological mechanisms operating in the different forms of ocular allergy. Recent published material has further characterized the roles that inflammatory and structural cells have in ocular allergic inflammation. Improved diagnostic methods have also been developed to assess the underlying causes of ocular allergy. SUMMARY: The underlying immune responses of ocular allergies are complex, indicating the critical need to understand the pathophysiology behind these diseases. Extensive research over the past several years has provided valuable insight into understanding the pathophysiology associated with the different forms of allergic conjunctivitis. Further clarification of the mechanisms associated with different forms of ocular allergy is essential for improved methods of classification, diagnosis, and treatment. PMID- 17873584 TI - Immunopathogenesis of ocular allergy: a schematic approach to different clinical entities. AB - PURPOSE OF REVIEW: The immunopathogenesis of ocular allergic disorders is generally related to the specific immunoglobulin E-mediated mast cell activation and the following cascade of inflammatory mediators. Seasonal and perennial allergic conjunctivitis, however, are the only ocular diseases to involve solely type I hypersensitivity. The other main forms, vernal and atopic keratoconjunctivitis, have a more complex immunological basis and a chronic inflammatory component. Involvement of inflammatory cells, particularly eosinophils and T cells, cytokines and proteases can lead to more serious corneal damage with vision-threatening potential. RECENT FINDINGS: Experimental allergic conjunctival models and clinical research studies have shown that T helper type 2 related mechanisms are definitely involved in the sensitization phase of ocular allergy, however, both T helper type 1 and type 2 cytokines are overexpressed in the active disease, contributing to the development of ocular inflammation. SUMMARY: A review of the recent literature allows us to better understand the mechanisms involved in the development of ocular allergy and to guide us toward a more schematic approach, which could possibly be useful in forming a new classification, standardizing clinical phases and individuating new treatment targets. PMID- 17873585 TI - Clinical grading of vernal keratoconjunctivitis. AB - PURPOSE OF REVIEW: The purpose of the present review is to provide an overview on the clinical features of vernal keratoconjunctivitis on the basis of cases series presented in the literature. Furthermore, a new grading system of vernal keratoconjunctivitis based on the severity of the disease is proposed. Different treatment options are discussed based on the clinical grade of vernal keratoconjunctivitis. RECENT FINDINGS: Recent epidemiological studies on the demographic, clinical and immunologic features of vernal keratoconjunctivitis are presented. The efficacy and complications of treatments are described. SUMMARY: Diagnosis and treatment of patients is a challenge for ophthalmologists as no precise diagnostic criteria have been established, the pathogenesis is unclear, and antiallergic treatments are often unsuccessful. This review describes old and new concepts of vernal keratoconjunctivitis diagnosis and treatment: the clinical features, the diagnostic criteria, the common features between this and other ocular allergies and the therapeutic strategies. On the basis of this knowledge, a new grading system is introduced based on clinical signs and symptoms of ocular surface inflammation. This new grading of vernal keratoconjunctivitis may help clinicians and researchers to classify disease activity and to establish a common agreement for treatments. PMID- 17873586 TI - Clinical grading of atopic keratoconjunctivitis. AB - PURPOSE OF REVIEW: Atopic keratoconjunctivitis (AKC), the most severe and chronic form of ocular surface allergy-related disorder, is the ocular surface complication that some atopic dermatitis patients can suffer. Its wide range of severity, from mild and occasional problems to persistent and intense inflammation, makes it difficult to appropriately select uniform patients for clinical studies. This article proposes a new classification system for AKC based on clinical severity. RECENT FINDINGS: Recent reports on AKC have contributed to a better understanding of the pathogenesis and clinical manifestations, and are offering new therapeutic candidates for AKC. No reports, however, have been found that address a classification of this disease. SUMMARY: A new definition and classification for AKC is presented by this review, based on clinical severity, grading the main symptoms and signs. It intends to serve as a first forum of discussion among clinicians and other scientists working in the field of ocular surface inflammation. The final intention is to have a common language helping develop efficient clinical trials leading to successful approval of new therapeutic compounds for this blinding ocular surface condition. PMID- 17873587 TI - Practical approach to diagnosis and treatment of ocular allergy: a 1-year systematic review. AB - PURPOSE OF REVIEW: A 1-year systematic review in the field of ocular allergy was carried out to select new information which may be useful for a practical approach to allergic conjunctivitis. RECENT FINDINGS: Out of the 56 articles listed by PubMed, 27 papers were included in the review following a consensus achieved among the authors who had independently reviewed all abstracts. Selected articles were classified according to their main focus: antihistamines, omalizumab, new treatments for vernal keratoconjunctivitis and inflammatory ocular disorders, and sublingual immunotherapy. SUMMARY: The data reviewed are discussed with the aim of underlining unmet needs and making recommendations for future studies on diagnosis and treatment of ocular allergy which may better guide clinical practice in this important area of allergy and clinical immunology. PMID- 17873588 TI - Future directions in therapeutic interventions for conjunctival inflammatory disorders. AB - PURPOSE OF REVIEW: To review recent advances in pathogenesis and treatment of conjunctival inflammatory disorders. RECENT FINDINGS: The conjunctiva becomes inflamed in a number of conditions, including allergy, atopy, dry eye, mucus membrane pemphigoid, Stevens-Johnson syndrome and surgical manipulation. Basic and clinical studies have identified a number of inflammatory mediators as potential therapeutic targets in these conditions. Additionally, new therapeutic agents and enhanced delivery systems have been evaluated. SUMMARY: Increased understanding of the key mediators of conjunctival inflammation coupled with improved drug delivery methods are leading to more effective therapy for conjunctival inflammatory disorders. PMID- 17873589 TI - Bibliography. Current world literature. Skin allergy. PMID- 17873591 TI - Anesthetics and brain protection. AB - PURPOSE OF REVIEW: There is a considerable risk of cerebral ischemia during anesthesia and surgery. Anesthetic agents have been shown to have a profound effect on the pathophysiology of cerebral ischemia. The present review provides a brief historical review and details new information about the anesthetic effects on the ischemic brain. RECENT FINDINGS: Although anesthetics have been shown to reduce ischemic cerebral injury, the durability of this neuroprotection has been questioned. Recent data indicate that, under the right circumstances, anesthetic neuroprotection can be sustained for at least 2-4 weeks; the durability of this protection is dependent upon the experimental model, control of physiologic parameters and the assurance of the adequacy of reperfusion. In addition, volatile anesthetics have been shown to accelerate postischemic neurogenesis; this suggests that anesthetics may enhance the endogenous reparative processes in the injured brain. SUMMARY: The available data indicate that anesthetics can provide long-term durable protection against ischemic injury that is mild to moderate in severity. Experimental data do not provide support for the premise that anesthetics reduce injury when the ischemic injury is severe. PMID- 17873592 TI - Intensive care management of patients with subarachnoid haemorrhage. AB - PURPOSE OF REVIEW: The aim of this article is to summarize recent concepts regarding the intensive care management of patients with subarachnoid haemorrhage, emphasizing the detection and treatment of cerebral vasospasm and the management of systemic complications. RECENT FINDINGS: Aneurysmal subarachnoid haemorrhage is a potentially devastating disease that requires complex treatment strategies and extended monitoring. The prognosis of subarachnoid haemorrhage depends on the severity of the initial bleed, the success of the procedure to secure the aneurysm and the occurrence and severity of sequelae, including cerebral vasospasm. Patients with subarachnoid haemorrhage benefit from multidisciplinary neurointensive care where management is targeted at securing the ruptured aneurysm, optimizing cardiovascular variables, detecting and treating cerebral vasospasm and managing systemic complications. SUMMARY: The complex treatment strategies applied after subarachnoid haemorrhage call for interdisciplinary collaboration between neurosurgeons, neuroradiologists, neurointensivists and specialist nurses. Specialized neuromonitoring and neuroimaging techniques must also be available. The neurointensive care unit serves as the focal point for these combined efforts. PMID- 17873593 TI - General anesthetic-induced neurotoxicity: an emerging problem for the young and old? AB - PURPOSE OF REVIEW: A growing body of evidence from cells, rodents, and sub-human primates suggests that general anesthetics can be neurotoxic to the developing and senescent brain. We review this evidence and put the studies into perspective for the practicing clinician. RECENT FINDINGS: Studies indicate that a variety of general anesthetics, which act primarily as gamma-amino-butyric acid receptor modulators and N-methyl-D-aspartic acid glutamate receptor antagonists, produce apoptotic neurodegeneration in the developing rodent and nonhuman primate brain. Vulnerability to this neurotoxicity is greatest during the period of synaptogenesis and presumably reflects disruption of the normal balance between excitation and inhibition during a critical period of brain development. Moreover, in the rodent, the neurodegeneration is associated with cognitive impairment into adulthood. Recent data also reveal that general anesthesia produces enduring cognitive impairment in aged but not young rodents and that halothane and isoflurane increase the generation and toxicity of amyloid beta, a protein strongly implicated in the pathogenesis of Alzheimer's disease. The meaning of these experimental results for human surgical patients is unclear, however, because human studies are lacking. SUMMARY: General anesthetics produce neurotoxicity and enduring cognitive impairment in young and aged animals but it is premature to change clinical practice because the issue has not been adequately studied in humans. PMID- 17873594 TI - Hypertonic saline solutions for treatment of intracranial hypertension. AB - PURPOSE OF REVIEW: This review aims to provide an update on recent knowledge gained on hypertonic saline solutions for the treatment of intracranial hypertension. Explanatory approaches to the mechanisms underlying the edema reducing effects of the solutions are outlined, practical aspects of use are presented, and trials that assessed their clinical utility are highlighted. RECENT FINDINGS: With an established trauma system, hypertonic saline added to conventional fluid resuscitation did not improve long-term outcome in multiple injury with hypotension and brain trauma. In intensive care, hypertonic saline reduced intracranial hypertension after subarachnoid haemorrhage, brain trauma, and a variety of other brain diseases, including cerebral edema in acute liver failure. SUMMARY: Hypertonic saline solutions have evolved as an alternative to mannitol or may be used in otherwise refractory intracranial hypertension to treat raised intracranial pressure. With high osmolar loads, the efficacy of the solution is enhanced, but no simple relationship between the saline concentration and the clinical effects of a solution is established. Caution is advised with high osmolar loads because they carry increased risks for potentially deleterious consequences of hypernatremia or may induce osmotic blood-brain barrier opening with possibly harmful extravasation of the hypertonic solution into the brain tissue. PMID- 17873595 TI - Current concepts of nociception: nociceptive molecular sensors in sensory neurons. AB - PURPOSE OF REVIEW: A large number of channels that are in some way linked to sensory transduction including nociception have been discovered in recent years. This review summarizes newly discovered channels that are implicated in nociception. Furthermore, details are discussed with emphasis on their possible application to clinical use as analgesics. RECENT FINDINGS: Studies with null mutant animals deficient in these channel genes reveal that the channels are indeed implicated in physiological as well as pathological nociception. SUMMARY: Many transient receptor potential channels are thermosensors that detect cold, warm and hot temperatures. These channels are activated not only by natural chemicals such as capsaicin, menthol, and camphor, but by various inflammatory signaling pathways. The acid-sensing ion channel and P2X channel that detect extracellular acidosis and ATP are also implicated in some types of pain. Voltage gated sodium or calcium channels draw attention because of their involvement in neuropathic pain. PMID- 17873596 TI - Nocebo hyperalgesia: how anxiety is turned into pain. AB - PURPOSE OF REVIEW: Nocebo hyperalgesia is a phenomenon that is opposite to placebo analgesia and whereby expectation of pain increase plays a crucial role. In recent times, both the neuroanatomical and the neurochemical bases of the nocebo effect and of nocebo-related effects have begun to be explored. Here, we highlight recent advances in our understanding of the neurobiology of the nocebo hyperalgesic effect. RECENT FINDINGS: A typical nocebo hyperalgesic response occurs following the administration of an inert substance which the subject believes to be a hyperalgesic agent (negative placebo or nocebo). It has been shown that the subject's negative expectations of pain worsening induce anticipatory anxiety about the impending pain increase and this triggers the activation of cholecystokinin that, in turn, facilitates pain transmission. Accordingly, cholecystokinin antagonists have been found to prevent this anxiety induced hyperalgesia. Brain-imaging studies have shown that the perceived intensity of a painful stimulus following negative expectations of pain increase is higher than in the absence of negative expectations and this is associated with changes in activation of specific brain regions. SUMMARY: Since pain appears to be amplified by anxiety through the activation of cholecystokininergic systems, new therapeutic strategies, such as new cholecystokinin antagonists, can be envisaged whenever pain has an important anxiety component. PMID- 17873597 TI - Update on the role of nonsteroidal anti-inflammatory drugs and coxibs in the management of acute pain. AB - PURPOSE OF REVIEW: Although NSAIDs have been shown to reduce postoperative analgesics, their ability to reduce opioid-related adverse effects and improve functional outcomes is questioned. Further, perioperative NSAID use may contribute to cardiovascular toxicity and impaired bone healing. This review highlights recent advances in our understanding of the role perioperative NSAIDs have on modulating nociception, their benefits when utilized as components of a multimodal analgesic regimen, and potential deleterious cardiovascular and osteogenic effects. RECENT FINDINGS: Recent research indicates that, in addition to peripheral blockade of prostaglandin synthesis, central inhibition of cyclooxygenase-2 may play an important role in modulating nociception. Although nonspecific NSAIDs provide analgesic efficacy similar to coxibs, their use has been limited in the perioperative setting because of platelet dysfunction and gastrointestinal toxicity. Coxibs may be a safer alternative in that setting. Both coxibs and traditional NSAIDs may contribute to a dose-dependent increase in cardiovascular toxicity and impaired osteogenesis. When used short term at the lowest effective dose, however, NSAIDs may provide for analgesic benefit without significant toxicity. SUMMARY: When utilized as a component of a multimodal analgesic regimen for acute pain, short-term NSAID administration reduces opioid related side effects and may contribute to improved functional outcomes without significant adverse effects. PMID- 17873598 TI - An update on the role of opioids in the management of chronic pain of nonmalignant origin. AB - PURPOSE OF REVIEW: To summarize and reflect over primarily recent epidemiological and randomized controlled trials in opioid-treated chronic nonmalignant pain patients, focusing on effects, side effects, risks and long-term consequences of the treatment. RECENT FINDINGS: In the western world opioids are increasingly being used for long-term treatment of chronic nonmalignant pain. While the long term benefits of opioids regarding pain relief, functional capacity and health related quality of life still remain to be proven, studies are emerging that describe serious long-term consequences such as addiction, opioid-induced hyperalgesia, cognitive disorders, and suppression of the immune and reproductive systems. SUMMARY: Much more research is needed concerning long-time effects and consequences of opioid therapy in chronic nonmalignant pain patients; however, some clear warning signals have been sent out within recent years. PMID- 17873599 TI - Gabapentin and pregabalin for chronic neuropathic and early postsurgical pain: current evidence and future directions. AB - PURPOSE OF REVIEW: Gabapentin and pregabalin bind to the alpha-2-delta calcium channel subunit and represent a novel analgesic drug class. The evidence base supporting their use for chronic neuropathic and early postsurgical pain is reviewed. RECENT FINDINGS: Multiple, large, high-quality trials have demonstrated the safety and efficacy of gabapentin and pregabalin in neuropathic pain. Treatment-related improvement of pain and sleep positively impact upon quality of life. Sedation, dizziness and ataxia are important and relatively common adverse effects, however. Accumulating evidence indicates that gabapentin, and possibly pregabalin, also exert important effects following surgery. Multiple high-quality trials have demonstrated analgesic and opioid-sparing efficacy with gabapentin following various surgical procedures. Gabapentin and pregabalin reduce movement evoked pain and this can lead to enhanced functional postoperative recovery. Postoperative opioid sparing is of questionable relevance since few trials have shown reduced opioid-related adverse effects. Sedation, dizziness and ataxia have been reported in only a few trials. Future larger-scale perioperative trials focused on safety assessment are needed, however. SUMMARY: Gabapentin and pregabalin are efficacious treatments for neuropathic and postsurgical pain. Future research addressing several specific questions would serve to better delineate their optimal roles in treating these and other pain conditions. PMID- 17873600 TI - Reassessment of the role of cannabinoids in the management of pain. AB - PURPOSE OF REVIEW: The aim of this article is to assess the role of cannabinoids in the treatment of acute and chronic pain in humans. RECENT FINDINGS: Very few clinical trials looking at the analgesic effects of cannabinoids in the acute pain settings have been performed. Three recent studies have evaluated the oral administration of synthetic cannabinoids in postoperative pain. At low doses cannabinoids are not different from placebo, whereas at high doses they may be associated with adverse effects or even worsening of pain intensity. In chronic pain patients, the safety and analgesic efficacy of a number of cannabinoid compounds have recently been evaluated in several clinical trials in several chronic pain conditions. While the small size of the trials and the relatively short duration of follow-up limits broad generalization, to date there is increasing evidence that cannabinoids are safe and effective for refractory chronic pain conditions including neuropathic pain associated with multiple sclerosis, rheumatoid arthritis, and peripheral neuropathy associated with HIV/AIDS. SUMMARY: The precise role of cannabinoids in pain treatment still needs further evaluation. Cannabinoid compounds may be more effective in the context of chronic neuropathic pain than for the management of acute pain. PMID- 17873601 TI - Genetic factors in pain and its treatment. AB - PURPOSE OF REVIEW: Genomic variations influencing basal pain sensitivity, the likelihood of developing chronic pain diseases as well as the response to pharmacotherapy of pain are currently under investigation Here, we review examples of promising approaches to diagnose genetic predisposition from recently published studies. RECENT FINDINGS: Candidate genes such as those for catechol-O methyltransferase, melanocortin-1 receptor, guanosine triphosphate cyclohydrolase and mu-opioid receptor have been intensively investigated, and associations were found with sensitivity to pain as well as with analgesic requirements in states of acute and chronic pain. In contrast, the impact of genetic variants of drug metabolizing enzymes on the response to pharmacotherapy is generally well described. Polymorphisms of the cytochrome P450 enzymes influence the analgesic efficacy of codeine, tramadol, tricyclic antidepressants and nonsteroidal antiinflammatory drugs. Together with further candidate genes, they are major targets of ongoing research in order to identify associations between an individual's genetic profile and drug response (pharmacogenetics). SUMMARY: The article reviews recent studies on genetic variables influencing pain and pharmacotherapy. Examples of promising candidate genes have been intensively studied during recent years. Although the number of subjects investigated is often small, published data and current advances in genotyping and study design suggest valid and clinically relevant results to date and even more in the future. PMID- 17873603 TI - Bibliography. Current world literature. Neuro anaesthesia. PMID- 17873602 TI - Current psychological approaches to the management of chronic pain. AB - PURPOSE OF REVIEW: To provide a review of the rationale and evidence supporting three frequently used psychosocial interventions for chronic pain: cognitive behavioral therapy, operant behavioral therapy and self-hypnosis training. We also review recent work in these areas, with an emphasis on the 2006 publishing year. RECENT FINDINGS: Recent clinical trials and laboratory work continue to support the use of cognitive-behavioral therapy and operant behavioral therapy as adjunctive treatments for chronic pain. Notable areas of new research include a novel program of systematic exposure to pain-related fear (such as fear of reinjury) and the adaptation of cognitive-behavioral therapy for special pain groups (e.g. juveniles and those with pain secondary to physical disability). Regarding self-hypnosis training, recent work suggests that hypnosis can provide temporary pain relief to the majority of individuals with chronic pain and that a substantial minority of these patients experience a clinically significant reduction in baseline pain over time. SUMMARY: Cognitive-behavioral therapy and operant behavioral therapy treatments focus on factors that exacerbate or maintain suffering in chronic pain, and should be considered as part of a multidisciplinary treatment paradigm. Self-hypnosis training may also be of benefit, although it appears to be no more (or less) effective than other relaxation strategies that include hypnotic elements. PMID- 17873605 TI - Primary liver cancers with nonalcoholic steatohepatitis. AB - Nine patients with hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) (six men and three women, median age 71.5 years) and one patient with intrahepatic cholangiocarcinoma (ICC), a 50-year-old man, in NASH are described. Most patients were associated with obesity, diabetes, hypertension, hypercholesterolemia, or hypertriglyceridemia. Seven patients showed insulin resistance and hyperinsulinemia. All patients except one met the criteria for metabolic syndrome. An HCC or ICC diagnosis was confirmed by tumor biopsy, surgery or autopsy except in two patients, who were diagnosed by computed tomography or hepatic angiography. The underlying liver disease was liver cirrhosis in six patients and chronic liver disease including mild hepatic fibrosis in four patients. The treatment of liver cancers consisted of surgery, radio-frequency ablation (RFA), transcatheter arterial embolization and transcatheter arterial infusion. Although the follow-up period was relatively short (median 27.5 months, average 32.1 months), all postoperative and post-RFA patients have not had a recurrence of HCC to date, except for one patient who had a palliative operation with intra-arterial infusion of anticancer drugs through an implanted reservoir port. Older age and liver cirrhosis are considered risk factors for HCC in NASH, and regular screening of these patients is necessary. Diabetes may contribute to the development of ICC in NASH. Curative therapy (surgery or RFA) and weight loss by the active therapeutic intervention (nutritional care and exercise therapy) after curative therapy may help us improve the prognosis of HCC in NASH. PMID- 17873606 TI - Variceal band ligation versus beta-blockers for primary prevention of variceal bleeding: a meta-analysis. AB - BACKGROUND/AIMS: Variceal band ligation (VBL) can reduce the rate of the first variceal by 45-52% compared with beta-blockers (BBs). We performed an updated meta-analysis of nine randomized controlled trials published as full papers, comparing VBL with BB for primary prevention. METHODS: Relative risk (RR) was computed using a random effects model. Sensitivity analysis was performed using a fixed effects model. Publication bias was also assessed using funnel plots and the rank correlation test. RESULTS: In total, 734 patients were studied (356, VBL; 378, BB). The pooled RR favoured VBL for first variceal bleed [0.63; 95% confidence interval (CI), 0.43-0.92] with number needed to treat being 13 (95% CI, 7-33), and for adverse events resulting in treatment withdrawal (0.24; 95% CI, 0.12-0.47) with the corresponding number needed to treat being 10 (95% CI, 6 25). Banding-related bleeding occurred in six patients (fatal in two). No difference was seen in bleeding-related deaths (RR, 0.71; 95% CI, 0.38-1.32), or overall mortality (RR, 1.09; 95% CI, 0.86-1.38). No significant heterogeneity or publication bias was present, and outcomes remained robust after sensitivity analyses. CONCLUSIONS: VBL was superior to BB in preventing the first variceal bleed, with fewer adverse events resulting in treatment discontinuation. Careful attention to technique and patient selection are important to minimize iatrogenic complications with VBL. VBL has a role in patients with poor drug compliance, or tolerance, and in those who bleed on BB therapy. PMID- 17873607 TI - Prognostic role of the initial portal pressure gradient reduction after TIPS in patients with cirrhosis. AB - BACKGROUND: The aim of this study was to determine the prognostic relevance of the portal pressure gradient (PPG) before and after transjugular intrahepatic portosystemic stent shunt (TIPS) insertion in patients with liver cirrhosis and recurrent oesophageal variceal bleeding. METHODS: 118 cirrhotic patients (Child A/B/C, 41/56/21; Child score, 7.7+/-2.0; baseline PPG, 21.8+/-4.7 mmHg) underwent TIPS for the prevention of variceal rebleeding. A multivariate logistic regression analysis was applied to identify the independent determinants of rebleeding and survival. The estimated rebleeding rate and the estimated survival were compared by log-rank testing. RESULTS: TIPS insertion reduced the PPG by 53.2+/-17.7%. During follow-up 21 patients suffered significant rebleeding (17.8%); bleeding-related mortality was 3.4% (four patients). The median survival [95% confidence intervals (CI)] was 48.2 (39.8; 60.8) months. The multivariate Cox model identified creatinine as the only independent predictor of survival, and the initial decrease of the PPG after TIPS as the only independent predictor of rebleeding. PPG before TIPS (21.8+/-4.7 mmHg) and the gradient at the time of rebleeding (22.0+/-2.9 mmHg) did not differ significantly. Patients with an initial decrease of the PPG after TIPS <30% were at the highest risk for rebleeding. Patients with an initial decrease of the PPG >60% rarely suffered from rebleeding. CONCLUSIONS: The initial decrease in the PPG after TIPS is a predictor for the risk of rebleeding but not for survival after TIPS. For that reason, in patients undergoing TIPS placement for the prevention of recurrent bleeding from oesophageal varices, an initial reduction of the PPG of 30-50% should be attempted. PMID- 17873608 TI - Pyogenic liver abscesses: mortality-related factors. AB - GOAL: To analyse the characteristics and mortality-related factors in a series of patients hospitalized for pyogenic liver abscess (PLA). BACKGROUND: Pyogenic liver abscesses are infrequent but potentially life threatening. Factors related to mortality have been less studied. STUDY: The medical records of 84 patients, 56 men and 28 women, mean age of 64.4 years (SD: 14) who were hospitalized between 1992 and 2005 owing to a PLA were reviewed. The past medical history, clinical signs and symptoms, laboratory values, imaging studies, microbiological features, treatment, complications and mortality were recorded. Factors related to complications and mortality were analysed. RESULTS: One or more bacteria were isolated in 65 patients (77.4%), being Streptococcus spp. (40.5%), Escherichia coli (27.4%), Klebsiella spp. (14.3%) and anaerobics (17.9%) the most frequent isolates. Complications developed in 60.7% of the cases, the most common one being a right pleural effusion (34.5%). Mortality rate was 19% (95% confidence interval: 10-28%). Mortality was associated with age (P=0.005), a previous history of coronary heart disease (P=0.016), absence of fever (P=0.001), development of sepsis and/or septic shock (P<0.001), raise of bilirubin levels (P=0.004), a biliary (P=0.035), or cryptogenetic origin (P=0.039), infection owing to E. coli (P=0.01) or to Candida (P=0.009) and development of pneumonia (P<0.001). Logistic regression revealed sepsis and/or septic shock as an independent risk factor for mortality. CONCLUSIONS: Mortality associated with PLA is high. The main risk factor for mortality is the development of sepsis and/or septic shock. PMID- 17873609 TI - Incidence, prevalence and clinical course of primary biliary cirrhosis in a Spanish community. AB - BACKGROUND AND AIMS: Primary biliary cirrhosis (PBC) is characterized by the autoimmune inflammatory response of small intrahepatic bile ducts. Prevalence in Spain is estimated as 61.9 cases per million inhabitants, whereas Northern Europe rates over 200 cases/million. Our objective was to determine the incidence and prevalence of PBC in our health area. MATERIAL AND METHODS: PBC was defined by the presence of abnormal liver tests (dissociated cholestasis) with positive antimitochondrial antibodies and/or compatible liver histology. Medical records from patients diagnosed between 1990 and 2002 were reviewed retrospectively. The following data were collected: diagnostic data, demographic and analytic data, liver histology and stage and treatment and disease outcome. RESULTS: In a population of 389 758 inhabitants, 87 patients were diagnosed with PBC. Mean age at diagnosis was 63.9+/-12.6 years. Eighty-four (96.6%) were women. Mean annual incidence was 17.2 per 10 inhabitants and the prevalence at the end of study was 195 per 10. Biopsy was performed in 71 (81.6%) patients, 61 of whom (86%) did not have fibrosis. Time of follow-up was 63.6+/-43.2 (2.28-153.9) months. CONCLUSION: Incidence and prevalence in our reference area are higher than in some Spanish areas, as per the results previously published; however, they are comparable with those obtained in Northern Europe and the US. PMID- 17873610 TI - Corticosteroid-dependent eosinophilic oesophagitis: azathioprine and 6 mercaptopurine can induce and maintain long-term remission. AB - BACKGROUND: Eosinophilic oesophagitis (EO) is a chronic inflammatory disorder of the oesophagus that is rapidly increasing in prevalence. Although systemic and topical corticosteroids are effective in treating EO, some patients develop corticosteroid dependency. Alternative therapeutic approaches that avoid corticosteroids are scarce. AIM: To analyse our experience at inducing and maintaining remission with an immunomodulatory therapy in steroid-dependent EO patients. METHODS: We analysed the clinical and histological response to azathioprine (AZA) and 6-mercaptopurine in three patients with EO (one also with eosinophilic gastroenteritis) and corticosteroid dependency. RESULTS: In all three patients, AZA or 6-mercaptopurine-induced clinical and histological remission that was maintained during the follow-up period (range 3-8 years). Two patients experienced relapses after ceasing AZA therapy. Remission, however, resumed when short-term corticosteroid treatment was followed by AZA. In all the patients, blood eosinophilia disappeared under AZA treatment. Only jumbo biopsies confirmed suspected EO with predominant muscle-layer involvement in one patient. CONCLUSION: In adult patients with corticosteroid-dependent EO, immunomodulatory treatment with purine analogues is a promising therapeutic approach for inducing and maintaining long-term remission without the need for further corticosteroids. Jumbo forcep biopsies might be needed to confirm a diagnosis of muscle-layer predominant EO. PMID- 17873611 TI - Diagnosing Barrett's oesophagus: factors related to agreement between endoscopy and histology. AB - BACKGROUND AND STUDY AIM: Few previous studies have addressed the agreement between endoscopy and histology regarding Barrett's oesophagus in unselected endoscopy patients. Our aim was to quantify this agreement, and to study its relation to clinical and endoscopic characteristics in consecutive patients coming for first-time gastroscopy. METHODS: We invited consecutive patients aged 18-79 years and endoscoped for the first time at endoscopy units exclusively serving defined catchment areas in southeast Sweden. Endoscopic and clinical data were recorded according to a predetermined protocol, and biopsies were taken from the distal oesophagus in all patients. RESULTS: Among 705 patients included, 17% [95% confidence interval (CI): 14-20] had endoscopically visible columnar mucosa above the oesophagogastric junction and 38% (95% CI: 34-42) had columnar mucosa in at least one biopsy irrespective of the endoscopic finding. The overall concordance between endoscopy and histology regarding presence (or absence) of columnar mucosa above the oesophagogastric junction was 74% (95% CI: 71-77) and the agreement beyond chance, as measured by Kappa (kappa) statistics, was fair, kappa=0.38 (95% CI: 0.32-0.45). The agreement between the endoscopic assessment and intestinal metaplasia at biopsy was 86% (95% CI: 83-88), but kappa was only 0.31 (95% CI: 0.21-0.41). Our data were consistent with a lower threshold for macroscopic detection of columnar epithelium above the oesophagogastric junction, when risk factors for Barrett's oesophagus were present. CONCLUSION: The agreement between macroscopic and microscopic assessments of Barrett's oesophagus is no more than fair, and partly dependent on the presence of patient characteristics suggestive of pathology in this region. PMID- 17873612 TI - Tumor pyruvate kinase isoenzyme type M2 and immunochemical fecal occult blood test: performance in screening for colorectal cancer. AB - OBJECTIVES: Immunochemical fecal occult blood test (FOBT) and determination of tumor pyruvate kinase isoenzyme type M2 (TuM2-PK) in stool samples may be valuable new screening tools for colorectal cancer (CRC). The aim of this study was to compare the accuracy of fecal TuM2-PK testing with immunochemical FOBT in patients with CRC or adenomas. METHODS: A total of 52 patients with CRC were analyzed, 47 with colorectal adenomas, and 63 matched controls with a normal colonoscopy. Nineteen additional patients with inflammatory bowel disease were tested to determine influence of inflammation. Stool samples were analyzed with two immunochemical FOBTs, Immo-care and OC-Light, and with a commercial enzyme linked immunosorbent assay for TuM2-PK. RESULTS: In patients with CRC, the sensitivity of TuM2-PK, Immo-care and OC-Light was respectively 85, 92 and 94%. In patients with adenomas, the sensitivity was respectively 28, 40 and 34%. Specificity for these tests was 90% for TuM2-PK and 97% for both immunochemical FOBTs. All tests showed a high positivity rate in patients with inflammatory bowel disease (79% for TuM2-PK and Immo-care, and 89% for OC-Light). CONCLUSION: Both immunochemical FOBTs appear valuable and are sensitive tests for CRC screening. TuM2-PK does not have supplemental value for screening for CRC because of a lower sensitivity and specificity. None of these tests is sensitive enough for detection of advanced adenomas. Patients with inflammatory bowel disease should be excluded from CRC screening when using immunochemical FOBT or TuM2-PK. PMID- 17873613 TI - P21WAF1/CIP1 expression in colorectal carcinomas is related to Kras mutations and prognosis. AB - BACKGROUND/AIM: P21WAF1/CIP1 is a cyclin-dependent kinase inhibitor activated by p53 to produce cell cycle arrest. A consensus has not been reached concerning the prognostic value of p21WAF1/CIP1 expression in colorectal cancers. PATIENTS/METHODS: P21WAF1/CIP1 expression was determined immunohistochemically in a series of 211 cases of colorectal carcinomas, together with its relation to p53, bcl-2, cell turnover (as assessed by Ki67 expression and apoptotic counts) and the Kras gene status. The expression of p21WAF1/CIP1 was also compared with reference to clinicopathological parameters and patient survival. RESULTS: The median value for nuclear p21WAF1/CIP1 expression was 31% (interquartile range, 13 47%) and the fraction of cases considered to be high expressers (>20%) was 66%. Expression of p21WAF1/CIP1 was not associated with immunoreactivity for p53 or bcl-2, or cell turnover. P21WAF1/CIP1 high-expressing tumors were more often well differentiated (P<0.001), node-negative (P=0.037), Dukes' B (P=0.027) and Kras gene-mutated cases (P=0.04). On univariate analysis, low p21WAF1/CIP1 expressers ( or = "sometimes" 57.1% vs. 33.1% after 1 week and 58.5% vs. 28.8% after 3 years; end of day, 61.1% vs. 41.0% after 1 week and 64.0% vs. 35.9% after 3 years [P<0.0001 for all comparisons]). After refitting, the proportion of subjects with dryness symptoms was stable. After 1 week, the presence of frequency of at least "sometimes" and severity of at least "moderate" during-the day and end-of-day dryness were significantly associated with study discontinuation (during-the-day frequency [P=0.007] and severity [P=0.017]; end of-day frequency [P=0.002] and severity [P=0.003]). CONCLUSIONS: Dryness symptoms improved after 1 week of refitting with lotrafilcon A and remained stable through 3 years. The presence of dryness after 1 week was associated with discontinuation from contact lens wear. Refitting with silicone hydrogel lenses reduced the frequency and severity of dryness symptoms seen with hydrogel lens wear for many subjects. PMID- 17873629 TI - Bubble and corneal dimple formation after the first overnight wear of an orthokeratology lens: a case series. AB - PURPOSE: To report the first documented case series of bubbles and corneal dimples associated with corneal reshaping after the first overnight wear of an orthokeratology lens. METHODS: Three cases of transient corneal dimples are described after the first overnight use of the Be Free orthokeratology lens (BE; Ultravision Pty. Ltd., Brisbane, Australia) related to bubble formation under the posterior lens surface. RESULTS: The corneal dimples were located most centrally and peripherally in correspondence to the reverse curve and did not produce a significant change in best-corrected visual acuity except in one patient, who had many bubbles in the central cornea. CONCLUSIONS: The current findings suggest that the precorneal tear film between the corneal surface and the posterior orthokeratology contact lens surface plays a role in the development of bubbles and corneal dimples. PMID- 17873630 TI - Corneal injury from a metallic foreign body: an occupational hazard. AB - PURPOSE: To describe a patient with a corneal injury from a metallic foreign body caused by negligence, and to highlight the importance of measures that must be taken to prevent corneal injuries. METHODS: A 21-year-old man experienced a foreign body sensation, pain, and redness in his left eye after he cut some iron material without using any eye protection. Slitlamp examination showed a thin, curled piece of iron material stuck into the cornea horizontally. The nasal part had penetrated the nasal tarsal conjunctiva below the upper lid. RESULTS: After removal of the foreign body, the cornea healed without scarring after a short follow-up. CONCLUSIONS: A corneal foreign body is a common cause of ocular morbidity and loss of working hours. Most workers do not use protective eyewear during work. By consistently wearing proper safety eyewear, which is the easiest and most effective preventive measure, loss of sight can easily be prevented after an eye injury. PMID- 17873631 TI - Orthokeratology-related infectious keratitis: a case series. AB - PURPOSE: To describe five patients who developed infectious keratitis after the use of overnight orthokeratology contact lenses. METHODS: Retrospective case report of five patients with infectious keratitis seen in Singapore National Eye Centre between 2001 and 2006. RESULTS: Five children between the ages of 9 and 14 years, who wore their lenses for an average of 1.5 months before developing orthokeratology-related infectious keratitis, were seen and treated at the Singapore National Eye Centre. All five patients had cultures that were positive for Pseudomonas aeruginosa. They were treated with fortified cefazolin (50 mg/mL) and gentamicin (14 mg/mL) and responded well, with resolution of the infectious keratitis. Although most patients had a best-corrected visual acuity of 20/40 or better after the resolution of the acute infection, they all showed a central or paracentral residual scar. CONCLUSIONS: Because of the safety issues involved, orthokeratology should be used with caution in children. PMID- 17873632 TI - Evaluating Medical Home constructs for children with special needs: integrating theory and logic models. AB - The Medical Home model for providing services to children with special healthcare needs has strong philosophical foundations, but the science supporting this theoretical model is not as well developed. The use of logic models and mixed method design provide systematic and rigorous approaches to observation while retaining the complexity, which tends to be lost with research designs intended to control and reduce the number of variables impacting a desired outcome, such as randomized controlled trials. This application provides a historical basis for applying logic models of evaluation and illustrates the utility of logic models. PMID- 17873635 TI - Parents' and caregivers' concerns about obesity in young children: a qualitative study. AB - To address the childhood obesity epidemic, it is necessary to understand parents' and caregivers' concerns and beliefs regarding their children's weight problems and best practices for addressing those concerns. Formative research methods were used to identify obesity-related concerns of Hispanic, Black, and White parents of young children (5-8 years old) in North Carolina. Participants identified challenges at multiple levels of influence. In all groups, participants reported that they had trouble finding enough time to help their children develop healthy lifestyles. Conflicting family priorities and needs often made it difficult to ensure that their children had healthy diets. Children's own diet and activity preferences and their parent or caregiver's inability to adequately guide their choices also contributed to obesigenic behaviors. In addition, many thought that physician and community support for their efforts to manage their children's eating habits was inadequate. Findings from these focus groups suggest that participants would be receptive to positive, multilevel prevention approaches to help their children attain and maintain healthy weights. PMID- 17873636 TI - Family function in families of children with Duchenne muscular dystrophy. AB - This article investigates the relationships of child- and family-related variables with family function in families with children who have Duchenne muscular dystrophy. Child-related variables included level of disability (indicator: Barthel Index) and age at diagnosis. Family-related variables included caregiver health status (indicator: Duke Health Profile), family income and employment, family support (indicator: Family APGAR), family hardiness (indicator: Family Hardiness Index), and family functioning (indicator: Family Assessment Device). Family function displayed a significant correlation with age at diagnosis, but not with disability level. It was also significantly correlated with family hardiness, caregiver health status, and levels of family support, but not with income or employment variables. These findings highlight the need to assist families to cope with the presence of serious illness in their children. PMID- 17873637 TI - The impact of chronic diseases: the partner's perspective. AB - A chronic physical disease not only has direct consequences for the chronically ill person but can also distort the life of the healthy partner. This study of a representative sample of chronically ill persons and their partners in the Netherlands presents quantitative information on the proportion of partners who experience consequences in 4 distinguished areas (personal life strain, social relations, financial burden, and intrinsic rewards) and provides insight into the factors related to this. Data were derived from a subsample (N = 1,093) of participants in the Dutch Panel of Patients With Chronic Diseases. Linear regression analysis was used to determine the relative effect of caregiving and of disease characteristics to explain the variance in the 4 impact factors. The most prevailing consequences, experienced by more than half of the partners, were related to personal life strain and intrinsic rewards. An impact on social relations and financial situation was reported by 20% of the partners. The regression analyses showed that the time spent on caregiving is the main predictor for all 4 impact measures in this study. However, the findings also make clear that the impact on the partner's life does not arise entirely from the amount of caregiving. An independent effect of specific disease characteristics is observed in addition to the effect of caregiving; that is, we found that physical impairments in the patient are related to higher personal life strain and higher financial burden whereas social impairments are related to higher impact on all 4 factors. When the patient's disease is accompanied with fatigue, the partner reports higher impact on personal life, on social relations, and on intrinsic rewards, and pain significantly affects the partner's social relations. Partners of patients with cancer, musculoskeletal, or digestive disorders are more vulnerable for the consequences of the chronic disease. The impact on female partners is higher for all 4 impact factors. The findings make clear that living with a chronically ill person has an impact on the partner's life that goes beyond the consequences of caregiving. PMID- 17873638 TI - Use of stigma, fear, and denial in development of a framework for prevention of HIV/AIDS in rural African American communities. AB - The epidemiology and demographics of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) have evolved over the last 25 years in the United States to include more women and minority populations, especially Latinos and African Americans. In addition, there has been a shift in HIV/AIDS cases from large northeastern and western metropolitan areas to persons living in rural areas and the south. The reasons for the changes and the shift are unclear, but major barriers to primary prevention strategies are most likely sociocultural. This article reviews some of the sociocultural barriers in HIV/AIDS prevention and presents a new approach or framework for addressing these barriers. The framework highlights Stigma, Fear, and Denial as barriers in interventions for HIV/AIDS targeted at African Americans living in rural Alabama. The framework uses a culturally competent, community-based approach. It is hoped that this framework could also be used as a model for addressing HIV/AIDS in other communities, as well as addressing other health disparities where stigma, fear, and denial may play a role, such as cancer, diabetes, heart disease, immunizations, and infant mortality. PMID- 17873639 TI - A qualitative study of how families decide to adopt household smoking restrictions. AB - Household smoking bans reduce exposure to secondhand smoke in adult nonsmokers and children. To explore the process families go through in adopting voluntary household smoking restrictions, qualitative interviews were conducted with rural African American and White adults in 102 households. The study investigated how families decide to restrict smoking in the home, who has significant influence in the decision-making process, the kinds of disagreements families have about household smoking restrictions, and reasons some families never consider household smoking policies. These findings have implications for designing intervention strategies and messages to promote household smoking bans and help family members negotiate smoke-free homes. PMID- 17873640 TI - Determinants of oral health behaviors among preuniversity (12th-grade) students in Yazd (Iran): an application of the health promotion model. AB - This study examined the relationships among behavior-specific cognitions and oral health behaviors using Pender's revised health promotion model. Subjects were 300 preuniversity students from 6 high schools in the Yazd district in central Iran. Suitable instruments were designed to measure concepts in the model through validity testing with an expert health panel, and reliability testing with a small sample of students (n = 30). Instruments then were administered to students. Model testing was conducted to identify factors affecting students' practice of oral health behaviors. The results from structural equation modeling indicated that behavior-specific cognitions and affect had a direct effect on oral health behaviors, except activity-related affects. Self-efficacy had an indirect effect on oral health behaviors through perceived barriers. Self efficacy mediated the effects of behaviors-specific cognitions and affect on oral health behaviors. Together, the variables accounted for 32% of the variance in oral health behaviors. Results of this study can be used to design and evaluate interventions to promote oral health behaviors among students. PMID- 17873641 TI - An ethical framework for community health workers and related institutions. AB - The aim of this article is to provide practical ethical guidance and to foster further critical reflection on ethical issues in the work, education, and training of community health workers. The analysis includes implications for associated institutions. We first summarize the roles of community health workers and some evaluations of their work. After next highlighting ethical elements from the literature, we then give a justification for the ethical framework that follows. The article then provides a detailed discussion of a set of basic ethical principles for the field of community health work. Among the principles, we argue that the following 3 should have a foundational role: equal and substantial respect, justice, and care. Among these, respect is most fundamental. PMID- 17873642 TI - Array-based comparative genomic hybridization: clinical contexts for targeted and whole-genome designs. AB - Array-based comparative genomic hybridization is ushering in a new standard for analyzing the genome, overcoming the limits of resolution associated with conventional G-banded karyotyping. The first genomic arrays were based on bacterial artificial chromosome clones mapped during the initial phases of the Human Genome Project. These arrays essentially represented multiple fluorescence in situ hybridization assays performed simultaneously. The first arrays featured a targeted design, consisting of hundreds of bacterial artificial chromosome clones limited mostly to genomic regions of known medical significance. Then came whole-genome arrays, which contained bacterial artificial chromosome clones from across the entire genome. More recently, alternative designs based on oligonucleotide probes have been developed, and all these are high-density whole genome arrays with resolutions between 3 and 35 kb. Certain clinical circumstances are well suited for investigation by targeted arrays, and there are others in which high-resolution whole-genome arrays are necessary. Here we review the differences between the two types of arrays and the clinical contexts for which they are best suited. As array-based comparative genomic hybridization is integrated into diagnostic laboratories and different array designs are used in appropriate clinical contexts, this novel technology will invariably alter the testing paradigm in medical genetics and will lead to the discovery of novel genetic conditions caused by chromosomal anomalies. PMID- 17873643 TI - High-resolution genomic microarrays for X-linked mental retardation. AB - Developments in genomic microarray technology have revolutionized the study of human genomic copy number variation. This has significantly affected many areas in human genetics, including the field of X-linked mental retardation (XLMR). Chromosome X-specific bacterial artificial chromosomes microarrays have been developed to specifically test this chromosome with a resolution of approximately 100 kilobases. Application of these microarrays in X-linked mental retardation studies has resulted in the identification of novel X-linked mental retardation genes, copy number variation at known X-linked mental retardation genes, and copy number variations harboring as yet unidentified X-linked mental retardation genes. Further enhancements in genomic microarray analysis will soon allow the reliable analysis of all copy number variations throughout this chromosome at the kilobase or single exon resolution. In this review, we describe the developments in this field and specifically highlight the impact of these microarray studies in the field of X-linked mental retardation. PMID- 17873644 TI - The evolution of molecular ruler analysis for characterizing telomere imbalances: from fluorescence in situ hybridization to array comparative genomic hybridization. AB - Submicroscopic telomere imbalances are a significant cause of mental retardation with or without other phenotypic abnormalities. We previously developed a set of unique telomere clones that identify imbalances in 3% to 5% of children with unexplained mental retardation and a normal karyotype. This targeted screening approach, however, does not provide information about the size or gene content of the imbalance. To enable such comprehensive characterization, a "molecular ruler" clone panel, extending up to 5 Mb proximal to the first telomere clone for each chromosome arm, was developed. This panel of clones was successfully used to delineate the size of unbalanced telomere aberrations in a fluorescence in situ hybridization assay. However, the fluorescence in situ hybridization analysis was quite labor-intensive, and for many cases, the imbalance extended beyond our 5-Mb coverage. Therefore, to develop a more efficient and comprehensive method for characterizing telomere imbalances, we developed a custom oligonucleotide microarray consisting of high-density coverage of all telomere regions as well as a whole-genome backbone. Overall, 44 pathogenic imbalances studied by fluorescence in situ hybridization or oligonucleotide array showed a size range of 400 kb to 13.5 Mb. In four of these, the array detected additional interstitial imbalances adjacent to the telomere imbalance, demonstrating the usefulness of added probe coverage. In 10 cases with benign imbalances inherited from a normal parent, the size ranged from 170 kb to 1.6 Mb. These results demonstrate that array comparative genomic hybridization will aid in more efficient and precise characterization of telomere imbalances leading to the development of gene dosage maps at human telomere regions for genotype/phenotype correlations. PMID- 17873645 TI - Detection of DNA copy number alterations in cancer by array comparative genomic hybridization. AB - Over the past few years, various reliable platforms for high-resolution detection of DNA copy number changes have become widely available. Together with optimized protocols for labeling and hybridization and algorithms for data analysis and representation, this has lead to a rapid increase in the application of this technology in the study of copy number variation in the human genome in normal cells and copy number imbalances in genetic diseases, including cancer. In this review, we briefly discuss specific technical issues relevant for array comparative genomic hybridization analysis in cancer tissues. We specifically focus on recent successes of array comparative genomic hybridization technology in the progress of our understanding of oncogenesis in a variety of cancer types. A third section highlights the potential of sensitive genome-wide detection of patterns of DNA imbalances or molecular portraits for class discovery and therapeutic stratification. PMID- 17873646 TI - Challenges in array comparative genomic hybridization for the analysis of cancer samples. AB - PURPOSE: To address some of the challenges facing the incorporation of array comparative genomic hybridization technology as a clinical tool, including archived tumor tissue, tumor heterogeneity, DNA quality and quantity, and array comparative genomic hybridization platform selection and performance. METHODS: Experiments were designed to assess the impact of DNA source (e.g., archival material), quantity, and amplification on array comparative genomic hybridization results. Two microdissection methods were used to isolate tumor cells to minimize heterogeneity. These data and other data sets were used in a further performance comparison of two commonly used array comparative genomic hybridization platforms: bacterial artificial chromosome (Roswell Park Cancer Institute) and oligonucleotide (Agilent Technologies, Santa Clara, CA). RESULTS: Array comparative genomic hybridization data from as few as 100 formalin-fixed, paraffin-embedded cells isolated by laser capture microdissection and amplified were remarkably similar to array comparative genomic hybridization copy number alterations detected in the bulk (unamplified) population. Manual microdissection from frozen sections provided a rapid and inexpensive means to isolate tumor from adjacent DNA for amplification and array comparative genomic hybridization. Whole genome amplification introduced no appreciable allele bias on array comparative genomic hybridization. The array comparative genomic hybridization results provided by the bacterial artificial chromosome and Agilent platforms were concordant in general, but bacterial artificial chromosome array comparative genomic hybridization showed far fewer outliers and overall less technical noise, which could adversely affect the statistical interpretation of the data. CONCLUSIONS: This study demonstrates that copy number alterations can be robustly and reproducibly detected by array comparative genomic hybridization in DNA isolated from challenging tumor types and sources, including archival materials, low DNA yield, and heterogeneous tissues. Furthermore, bacterial artificial chromosome array comparative genomic hybridization offers the advantage over the Agilent oligonucleotide platform of presenting fewer outliers, which could affect data interpretation. PMID- 17873647 TI - Controversies and challenges of array comparative genomic hybridization in prenatal genetic diagnosis. PMID- 17873648 TI - Structural variation in the human genome: the impact of copy number variants on clinical diagnosis. AB - Over the past few years, the application of whole-genome scanning array technologies has catalyzed the appreciation of a new form of submicroscopic genomic imbalances, referred to as copy number variants. Copy number variants contribute substantially to genetic diversity and result from gains and losses of genomic regions that are 1000 base pairs in size or larger, sometimes encompassing millions of bases of contiguous DNA sequences. As genome-wide scanning techniques become more widely used in diagnostic laboratories, a major challenge is how to accurately interpret which submicroscopic genomic imbalances are pathogenic in nature and which are benign. Herein, we review the literature from the past 3 years on this new source of genomic variability and comment on factors that should be considered when trying to differentiate between a pathogenic and a benign copy number variant. PMID- 17873649 TI - The discovery of microdeletion syndromes in the post-genomic era: review of the methodology and characterization of a new 1q41q42 microdeletion syndrome. AB - PURPOSE: The advent of molecular cytogenetic technologies has altered the means by which new microdeletion syndromes are identified. Whereas the cytogenetic basis of microdeletion syndromes has traditionally depended on the serendipitous ascertainment of a patient with established clinical features and a chromosomal rearrangement visible by G-banding, comparative genomic hybridization using microarrays has enabled the identification of novel, recurrent imbalances in patients with mental retardation and apparently nonspecific features. Compared with the "phenotype-first" approach of traditional cytogenetics, array-based comparative genomic hybridization has enabled the detection of novel genomic disorders using a "genotype-first" approach. We report as an illustrative example the characterization of a novel microdeletion syndrome of 1q41q42. METHODS: We tested more than 10,000 patients with developmental disabilities by array-based comparative genomic hybridization using our targeted microarray. High-resolution microarray analysis was performed using oligonucleotide microarrays for patients in whom deletions of 1q41q42 were identified. Fluorescence in situ hybridization was performed to confirm all 1q deletions in the patients and to exclude deletions or other chromosomal rearrangements in the parents. RESULTS: Seven cases were found with de novo deletions of 1q41q42. The smallest region of overlap is 1.17 Mb and encompasses five genes, including DISP1, a gene involved in the sonic hedgehog signaling pathway, the deletion of which has been implicated in holoprosencephaly in mice. Although none of these patients showed frank holoprosencephaly, many had other midline defects (cleft palate, diaphragmatic hernia), seizures, and mental retardation or developmental delay. Dysmorphic features are present in all patients at varying degrees. Some patients showed more severe phenotypes and carry the clinical diagnosis of Fryns syndrome. CONCLUSIONS: This new microdeletion syndrome with its variable clinical presentation may be responsible for a proportion of Fryns syndrome patients and adds to the increasing number of new syndromes identified with array-based comparative genomic hybridization. The genotype-first approach to identifying recurrent chromosome abnormalities is contrasted with the traditional phenotype first approach. Targeting developmental pathways in a functional approach to diagnostics may lead to the identification of additional microdeletion syndromes. PMID- 17873650 TI - Oligonucleotide arrays for high-resolution analysis of copy number alteration in mental retardation/multiple congenital anomalies. AB - Genetic diseases arising from microdeletions and microduplications lead to copy number alterations of genomic regions containing one or more genes. Clinically, these rearrangements may be detected by routine cytogenetic testing, which may include karyotype analysis, subtelomeric analysis with fluorescence in situ hybridization, and/or fluorescence in situ hybridization directed at known chromosomal rearrangement-based disorders. The major limitations of these tests are low resolution and limited coverage of the genome. Array-based comparative genomic hybridization has recently become a widely used approach in the genome wide analysis of copy number alterations in children with mental retardation and/or multiple congenital anomalies. Oligonucleotide-based arrays provide a genome-wide coverage at a much higher resolution than microarrays currently used in clinical diagnostics, greatly improving the rate of detection of submicroscopic copy number alterations in children with mental retardation and/or multiple congenital anomalies. PMID- 17873651 TI - Ethical implications of array comparative genomic hybridization in complex phenotypes: points to consider in research. AB - As with many new diagnostic technologies, the recent rapid emergence of array comparative genome hybridization in clinical genetics provides the power to observe new biological phenomena before their clinical significance is well understood. This raises ethical issues for clinicians when applying the technologies. However, at this early stage of research and development on array comparative genome hybridization, the ethical implications of the conduct of research, as well as how research findings are presented and interpreted, should also be considered by the research, clinical, and ethics communities. These considerations are especially important in the use of array comparative genome hybridization to study complex and common traits. We examined recent publications on autism as an example of the application of array comparative genome hybridization to a complex phenotype. Our goal was to identify points to consider for researchers, clinicians, and patients/families to ensure responsible and ethical design, presentation, and interpretation of these kinds of studies. PMID- 17873652 TI - Comprehensive validation of array comparative genomic hybridization platforms: how much is enough? AB - Clinical testing using various array comparative genomic hybridization platforms is being incorporated rapidly into cytogenetic testing algorithms. Comprehensive validation of these complex assays presents unique challenges and very few studies reporting the validation of commercially available array platforms have been published. Sixty-seven patients with previously defined subtelomere abnormalities, representing deletions and/or duplications of all 41 clinically relevant sites, were tested in a blinded study using the Spectral Genomics Constitutional Chip 3.0. Overall, 72 of 74 (97%) subtelomeric abnormalities were concordant with previous cytogenetic studies. However, two false-negative results were documented, and issues with mismapped and suboptimal clone performance were identified that may result in failure to detect 6q and 20q subtelomeric abnormalities. The results of this study indicate that comprehensive validation is necessary before implementation of array comparative genomic hybridization platforms into a clinical setting. Specific suggestions for validation are discussed in the context of the recently proposed American College of Medical Genetics guidelines for microarray analysis for constitutional cytogenetic abnormalities. PMID- 17873653 TI - Array comparative genomic hybridization and computational genome annotation in constitutional cytogenetics: suggesting candidate genes for novel submicroscopic chromosomal imbalance syndromes. AB - Genome-wide array comparative genomic hybridization screening is uncovering pathogenic submicroscopic chromosomal imbalances in patients with developmental disorders. In those patients, imbalances appear now to be scattered across the whole genome, and most patients carry different chromosomal anomalies. Screening patients with developmental disorders can be considered a forward functional genome screen. The imbalances pinpoint the location of genes that are involved in human development. Because most imbalances encompass regions harboring multiple genes, the challenge is to (1) identify those genes responsible for the specific phenotype and (2) disentangle the role of the different genes located in an imbalanced region. In this review, we discuss novel tools and relevant databases that have recently been developed to aid this gene discovery process. Identification of the functional relevance of genes will not only deepen our understanding of human development but will, in addition, aid in the data interpretation and improve genetic counseling. PMID- 17873654 TI - Use of array-based technology in the practice of medical genetics. AB - Mental retardation affects approximately 3% of the population, and the background birth defect rate is 3% to 4%. An underlying cause is identified less than 50% of the time. In the cases in which a cause is determined, a chromosomal anomaly is the cause in up to 40%. Laboratory evaluation routinely includes high-resolution karyotyping, subtelomeric fluorescence in situ hybridization analysis, and targeted fluorescence in situ hybridization analysis depending on the clinical features. There are technical limitations to these techniques, however. For example, anomalies less than 2 to 3 Mb in size are undetectable by karyotype, and subtelomeric fluorescence in situ hybridization analysis is a labor-intensive analysis with a relatively low yield. With completion of the Human Genome Project, diagnostic testing is moving toward the use of DNA-based techniques such as comparative genomic hybridization microarray analysis or array comparative genomic hybridization. Although this technology has been used in the evaluation of tumors and cancer patients in the past, it is now being applied in the assessment of patients demonstrating idiopathic mental retardation or developmental delay, dysmorphic features, congenital anomalies, and spontaneous abortions. As with other well-developed cytogenetic studies, there are technical limitations to array comparative genomic hybridization that must be acknowledged and addressed before its widespread use. A variety of array-based technologies are now available on a clinical basis. We discuss the utility and limitations of using this technology in the evaluation of individuals with mental retardation and malformations, citing the existing literature. PMID- 17873655 TI - Microarray analysis for constitutional cytogenetic abnormalities. PMID- 17873659 TI - Reinventing CME: the role of the care pilot in the medical group practice. AB - This article recommends that the content of traditional continuing medical education be changed significantly to include the concepts and skills necessary to enable practice teams to feedback information into the practice, which would result in the creation of a learning organization with the ability to plan for and anticipate future activities. The primary role in this new organization would be called a care pilot who would have as a primary responsibility, the successful navigation and improvement of the 6 aims as spelled out in the Institute of Medicine report Crossing the Quality Chasm. PMID- 17873660 TI - Organizational technologies for transforming care: measures and strategies for pursuit of IOM quality aims. AB - Progress on the Institute of Medicine's (IOM's) 6 aims to bridge the "quality chasm" requires both measurement and the concerting of multiple organizational technologies. The basic thesis of this article is that rapid progress on the IOM's multiple aims calls for transformative change within and among healthcare organizations. The promise of a number of types of transformative approaches is closely linked to their ability to simultaneously build upon several organizational technologies: clinical, social, information, and administrative technologies. To encourage and advance such efforts, this article identifies illustrative measures of attainment of the IOM's 6 aims or targeted areas for improvement that reflect the contributions of the 4 organizational technologies. It discusses examples of relationships between the IOM aims and the organizational technologies considered. Finally, the article offers illustrations of the interplay of these organizational technologies and IOM aims-across an array of organizational innovations with transformative potential. Included among such innovations are information technology in the form of electronic medical records, computer-based physician order entry, and patient health records; organization-wide patient-centered cultural change such as Studer's Hardwiring Excellence; Six Sigma and Toyota Production Management/LEAN; major clinical technology change, for example, minimally invasive cardiac surgery and broader treatment innovations such as disease management. PMID- 17873661 TI - Use of patient-reported outcomes in clinical oncology practice: a nonvisit approach to patient care based on the IOM report. AB - The Institute of Medicine report, Crossing the Quality Chasm, suggested some new ways of thinking about organizing care. This article describes how practices might create continuous healing relationships using methods that are independent of patient visits to monitor and address problems that may occur during cancer care. Such a system would be based on patient report, timely and useful, sensitive to change, and low burden for patients, clinicians, and administrative staff. Furthermore, it would be built into the delivery of care and be integrated with other data systems such as patient records, decision support, and community or other resources. Using reports for patients that are presented in a format that is easily understandable, patients should be able to monitor their own progress. PMID- 17873662 TI - Healthcare utilization among veterans undergoing chemotherapy: the impact of a cancer care coordination/home-telehealth program. AB - The 2001 Institute of Medicine report indicted that the US healthcare system fails to provide high-quality care, and offered 6 aims of improvement that would redesign the delivery of care for the 21st century. This study compared the use of Department of Veterans Affairs (VA) inpatient and outpatient services of cancer patients enrolled in a Cancer Care Coordination/Home-Telehealth (CCHT) program that involved remote management of symptoms (eg, emotional distress, pain) via home-telehealth technologies to a control group of cancer patients receiving standard VA care. Using a matched case-control design, 2 control patients per case were selected, matched by tumor type and cancer stage. There were 43 Cancer CCHT patients and 82 control group patients. Based on a medical record review of each patient, the total number of cancer-related services (defined as visits that were expected given the patients' cancer diagnosis and treatment protocol) and preventable services (defined as visits needed outside of those expected given the cancer diagnosis and planned treatment) were calculated over a 6-month period. Poisson multivariate regression models were used to estimate the adjusted relative risks (RRs) for the effects of the Cancer CCHT program on the service use outcomes. Cancer CCHT patients had significantly fewer preventable services (clinic visits: RR = 0.03, 95% confidence interval [CI] = 0.00-0.24; bed days of care (BDOC) for hospitalization [all-cause]: RR = 0.50, 95% CI = 0.37-0.67; hospitalizations [chemotherapy related]: RR = 0.43, 95% CI = 0.21-0.91; and BDOC for hospitalizations [chemotherapy related]: RR = 0.49, 95% CI = 0.34-0.71) than the control group. This study offered some preliminary evidence that patients enrolled in a Cancer CCHT program can successfully manage multiple complex symptoms without utilizing inpatient and outpatient services. PMID- 17873663 TI - Comprehensive approach to automated assistive telemanagement for seniors in their home or residence-pilot program results. AB - A comprehensive pilot study was conducted to examine how remote senior monitoring of important vitals information and virtual nurse visits conducted remotely via videophone would improve seniors' adherence to care plan and enable them to remain in their homes longer. Recruitment of study individuals was conducted in the North Shore area of Chicago, Ill. Eleven seniors participated in this small scale study to keep scale issues controlled. Of the 11 participants, 8 were female. The average age was 80+ (64-89) with participants suffering from an average of 4.4 chronic conditions and requiring assistance in 3.4 activities of daily living. PMID- 17873664 TI - Innovative approach to the aims for improvement: emergency department patient throughput in an impacted urban setting. AB - Los Angeles County is in crisis with its emergency ambulatory care. Many barriers exist at the hospital level that affect patient throughput. A case study is presented for St. Francis Medical Center, a 384-bed hospital in southeast Los Angeles. Its governing board has put out a call to have its emergency department oversee intraprocess and interprocess improvements to enhance patient movement through the system. These innovative front- and back-end initiatives are examined using the Institute of Medicine's Six Aims for Improvement. Details on each of the initiatives are provided along with how the leadership monitors the progress. PMID- 17873665 TI - Diagnostic errors and abnormal diagnostic tests lost to follow-up: a source of needless waste and delay to treatment. AB - Diagnostic errors are an important and often underappreciated source of medical error, needless delays to treatment, and needlessly wasted resources. Almost 65% of diagnostic errors have an important contribution of system errors, of which many are an abnormal test result that was lost to follow-up, that is, missed results. These system problems that contribute to missed results may represent low-hanging fruit for those who wish to reduce diagnostic errors in their institution. The rate of missed results and associated treatment delay are discussed. The system factors and human factors that contribute to these errors are discussed along with strategies that can be adopted to reduce these errors. PMID- 17873666 TI - How often are physicians and chiropractors provided with patient information when accepting referrals? AB - The objective of our study is to document how often MD/DOs and doctors of chiropractic (DCs) receive patient information from referring MD/DOs and DCs and highlight to what extent there is a lack of formal intraprofessional and interprofessional referral relationships between MD/DOs and DCs. A total of 517 MD/DOs and 452 DCs participated in this study. The study results suggest that patient information is not regularly provided by either MD/DOs or DCs, even when making formal referrals to a provider of the same type. This was more pronounced when MDs made formal referrals to DCs. PMID- 17873667 TI - Facilitators and barriers to improving interprofessional referral relationships between primary care physicians and chiropractors. AB - OBJECTIVE: Findings from recent studies suggest that there are poor interprofessional referral relationships between primary care physicians (MDs) and chiropractors (DCs) and this can lead to fragmentation of care. The objective of this study is to identify potential facilitators and barriers to developing positive interprofessional referrals relationships between MDs and DCs. METHODS: We conducted 2 rounds of focus group interviews on a convenience sample of MDs and DCs. The focus groups were audiotaped, and transcripts were prepared for each focus group interaction. These data were analyzed through content analysis by 2 independent evaluators to determine the key themes and concepts provided by the focus groups. RESULTS: Both MDs and DCs suggested that good communication, openness to discussion by providers, and patient interest are key factors for developing positive interprofessional referral relationships and implementing interprofessional practice-based research networks. Barriers to interprofessional relationships include lack of good communication between the 2 provider types, bias toward alternative medicine, lack of knowledge or understanding of chiropractic care, geographic constraints, and economic considerations. CONCLUSIONS: This study identified several facilitators and barriers for developing positive referral relationships between primary care physicians and chiropractors. Future studies must focus on demonstrating the role of these factors on developing positive interprofessional relationships. PMID- 17873669 TI - Rights Group uncovers link between women' rights and HIV infection. PMID- 17873670 TI - Measuring movement disorders in antipsychotic drug trials: the need to define a new standard. PMID- 17873671 TI - Revisiting the 5 dimensions of the Positive and Negative Syndrome Scale. AB - BACKGROUND: The Positive and Negative Syndrome Scale (PANSS) is a widely used instrument to measure severe psychopathology in schizophrenia. Recently, its widely accepted 5-factor solution is questioned using confirmatory factor analysis (CFA). This article examines the appropriateness of applying CFA to PANSS data and the dimensionality of the PANSS in a large sample of persons with chronic schizophrenia, schizophreniform disorder, and schizoaffective disorder. MATERIALS AND METHODS: Data reduction was conducted on PANSS baseline assessments from 2 multicenter clinical trials consisting of 1284 persons' available PANSS data at baseline and Week 8. Supplementary analyses were conducted for separate trials and for noncompleters at baseline (n = 1872). RESULTS: Examination of the data indicated that the statistical requirements of CFA (eg, multivariate normality) were not met by the data. Multidimensional scaling and a scree plot of principal components superimposed on simulated random data converged to indicate that 5 dimensions are generally a parsimonious fit to the PANSS at baseline, whereas 4 dimensions emerged after 8 weeks of treatment. The components included negative symptoms, positive symptoms, disorganized (baseline only), anxiety/depression, and excited. CONCLUSIONS: The results demonstrate realistic alternatives to CFA when studying the PANSS, support a 5-component model of PANSS ratings at baseline, and indicate that the structure of symptoms change after 8 weeks of treatment. These results seem to be robust because they generally replicate within trials for completers and at baseline for the entire sample. PMID- 17873673 TI - Efficacy of a new oral lubricant solution in the management of psychotropic drug induced xerostomia: a randomized controlled trial. AB - OBJECTIVE: Xerostomia is a subjective sensation of mouth dryness often occurring as an unwanted effect of psychotropic drugs. METHODS: The clinical efficacy and acceptability of a new oxygenated glycerol triester (OGT) oral spray (1 or 2 sprays up to 4 times daily) in the treatment of xerostomia was compared with those of a commercially available artificial saliva substitute (ASS [Saliveze]) in a 2-week, open-labeled, randomized, parallel-group study. Clinical assessment of xerostomia included evaluation of mouth dryness by means of a 10-cm-long visual analog scale, objective blinded assessment of the oral tissue condition by a dental hygienist by means of a 4-point ordinal scale, and subjective patient based assessment of dry mouth symptoms by means of dichotomous responses to a questionnaire. [Day 14 - baseline] patient-based mouth dryness score was the primary end point. RESULTS: Seventy-four patients (41 women and 33 men, 44 +/- 15 years) undergoing long-term psychotropic drug treatment were consecutively enrolled. At day 14, OGT resulted in better efficacy than ASS in mouth dryness score (mean difference, 1.2 +/- 0.4; P = 0.006), speech difficulties (mean difference, 1.2 +/- 0.4; P = 0.005), taste (mean difference, 1.1 +/- 0.4; P = 0.02), and overall mouth condition (mean difference, 1.4 +/- 0.9; P = 0.005). Taste of OGT was better than that of ASS (mean difference, 1.4 +/- 0.6; P = 0.04), as was OGT acceptability (mean difference, 1.4 +/- 0.9; P = 0.005). CONCLUSION: Oxygenated glycerol triester lubricant oral spray was superior to a commercially available ASS in improving xerostomia and overall condition of the oral tissue. PMID- 17873675 TI - Safety and efficacy of escitalopram in the treatment of premature ejaculation: a double-blind, placebo-controlled, fixed-dose, randomized study. AB - PURPOSE: To evaluate the efficacy and safety of most selective serotonin reuptake inhibitor drug, escitalopram, in delaying ejaculation in patients with premature ejaculation (PE). MATERIALS AND METHODS: A total of 276 married men (mean age, 34.4 years) with PE were randomly assigned to receive 10 mg of escitalopram (n = 138; Group 1) or placebo (n = 138; Group 2) for 12 weeks. Pretreatment evaluation included history and physical examination, intravaginal ejaculatory latency time (IELT), International Index of Erectile Function (IIEF), and Meares-Stamey test. The efficacy of 2 treatments was assessed every 2 weeks during treatment, at the end of study, and in 3- and 6-month follow-up after cessation of treatment. RESULTS: At the end of 12-week treatment, the escitalopram group had a 4.9-fold (95% confidence interval [CI], 3.14-6.12) increase of the geometric mean IELT, whereas after placebo, the geometric mean IELT did not increase significantly (1.4-fold increase; 95% CI, 0.86-1.68; P = 0.001). Baseline mean intercourse satisfaction domain values of IIEF 10 and 11 reached to 16 and 10 at 12-week treatment in Groups 1 and 2, respectively (P = 0.01). At the end of 6-month follow-up period, the geometric mean IELT in escitalopram and placebo group demonstrated 3.1- (95% CI, 2.16-4.4) and 1.3-fold (95% CI, 0.78-1.62) increase, respectively (P = 0.001). Three- and 6-month intercourse satisfaction domain values of IIEF were 15 and 14 in Groups 1 and 10 and 10 (P = 0.01) in Group 2, respectively. Mean number of adverse events was 22 for escitalopram and 9 for placebo (P = 0.04). CONCLUSIONS: Oral escitalopram is an effective treatment for PE with long-term benefit for the patient after it is withdrawn. Further studies are required to draw final conclusions on the efficacy of this drug in PE. PMID- 17873676 TI - Selective serotonin reuptake inhibitor discontinuation: side effects and other factors that influence medication adherence. AB - OBJECTIVE: Patients with major depression discontinue taking their antidepressants for many reasons. Although side effects are often cited as the reason for discontinuation, few prospective studies have addressed this question, and none has specifically examined discontinuation in patients with severe depression. METHOD: Inpatients and outpatients treated with a selective serotonin reuptake inhibitor for major depressive disorder were identified after admission. Three months later, patients were contacted and interviewed to determine antidepressant usage and the side effects experienced, including when these were experienced and their severity. RESULTS: Between October 2001 and April 2003, 406 English- or Spanish-speaking patients aged 18 to 75 years were followed up. One in 4 patients discontinued the index antidepressant. Among specific side effects noted, only "change in weight" and "anxiety" were significant predictors of discontinuation after controlling for confounders. Experiencing 1 or more "extremely" bothersome side effects was associated with more than a doubling of the risk of discontinuation, but the presence of side effects and side effects less severe than "extremely" bothersome were not significant predictors. There were no differences among selective serotonin reuptake inhibitor antidepressants in either the presence/absence of side effects or in the discontinuation rates. CONCLUSION: The results suggest that the contribution of side effects to antidepressant discontinuation is more complex than previously suggested. Disparate findings from earlier studies may reflect aspects of study design, such as examining populations whose severity of depression varied widely or not controlling for important confounding factors. Future research should separately examine high-risk groups (or control for severity of depression) and carefully rule out other potential contributors to discontinuation. PMID- 17873677 TI - Do formulation differences alter abuse liability of methylphenidate? A placebo controlled, randomized, double-blind, crossover study in recreational drug users. AB - The primary objective of this study was to determine if the abuse liability of methylphenidate is governed by formulation differences that affect rates of drug delivery. In this double-blind, placebo-controlled, randomized, crossover study, subjects with a history of recreational drug use received single oral doses of placebo, 60 mg of immediate-release methylphenidate (IR) and 108 mg of extended release methylphenidate (osmotic release oral system [OROS]). Over 24 hours after dosing, blood was collected to determine plasma concentrations of methylphenidate, and subjects completed subjective assessments of abuse liability (Addiction Research Center Inventory, Drug Rating Questionnaire-Subject, and Subjective Drug Value). The abuse-related subjective effects of IR and OROS methylphenidate were statistically significantly different from placebo, confirming the overall validity of the study. Although a higher dose of OROS methylphenidate was used compared with IR methylphenidate (108 mg vs 60 mg), subjective effects were consistently lower for OROS compared with IR methylphenidate (statistically significant for 3 of 6 measures of positive effects), particularly at early time points. In general, pharmacokinetic pharmacodynamic parameters were correlated from a poor to modest degree, with greater correlations observed for IR methylphenidate. In addition, a post hoc "qualification" method was developed, which demonstrated that pharmacological qualification might improve the assessment of subjective effects. Although requiring epidemiological confirmation, the results suggest that OROS methylphenidate, with its characteristic slow ascending plasma concentration profile, may have lower abuse potential. This conclusion is reflected by lower subjective responses during early hours as compared with the IR formulation with its rapid drug delivery and accompanying greater subjective effects. PMID- 17873678 TI - Effectiveness of low-dose naltrexone in the post-detoxification treatment of opioid dependence. AB - BACKGROUND: The clinical use of naltrexone (NTX) in the treatment of opioid dependence has been limited because of poor compliance and inconsistent outcomes. In particular, the therapeutic benefit of extended treatment with NTX after opioid detoxification is unclear. The present study evaluated whether the augmentation with low-dose NTX during the post-detoxification treatment of opioid dependence would improve outcomes. METHODS: In an open-label naturalistic design, 435 opioid-dependent patients who had completed inpatient detoxification were offered the choice of entering 1 of the 2 outpatient treatment arms: clonidine extended treatment (CET) (clonidine + psychosocial treatment), or enhanced extended treatment (EET) (oral NTX [1-10 mg/d] + CET) for 21 days. The primary outcome measure was retention in treatment. Secondary outcomes included abstinence from opioids, dropouts, and adherence to postdischarge care. RESULTS: One hundred sixty-two patients (37.2%) accepted EET. Subjects receiving EET stayed longer in the program (F = 64.4; P = 0.000), were less likely to drop out, used less opioids, and followed through with referral to long-term outpatient treatment in a higher number, compared with patients in the CET arm (P = 0.000 in each case). The NTX + clonidine combination was safe and well tolerated. CONCLUSIONS: This preliminary study indicates the potential benefit of augmentation with low-dose NTX to improve outcomes after opioid detoxification for a preferred group of patients. Randomized controlled trials are necessary to further evaluate the role of low-dose NTX in the outpatient treatment of opioid dependence. PMID- 17873679 TI - Influence of topiramate on olanzapine-related weight gain in women: an 18-month follow-up observation. AB - In a randomized controlled trial, we compared the efficacy of topiramate versus placebo in women undergoing olanzapine therapy and found that topiramate effectively contributed to weight loss in short-term treatment and had a positive effect on health-related quality of life, the patients' actual state of health, and psychological impairments. The aim of this observational study was to assess whether topiramate has a sustained benefit in long-term treatment of olanzapine associated weight gain in subjects who had participated in the previous randomized controlled trial comparing topiramate with placebo. The subjects (topiramate group, n = 25; former placebo group, n = 18) were observed in an 18 month open-label study. After unblinding, subjects from the former topiramate group continued treatment with topiramate, whereas subjects from the former placebo group received neither placebo nor topiramate. The subjects were seen every 6 months, weighed, and tested with the SF-36 Health Survey, Scale of Well Being, and the Adjective Checklist. According to the intent-to-treat principle, the repeated-measures analysis showed a significant interaction for the group-by time effect for change of weight (P < 0.01) on the Scale of Well-Being (P < 0.01), all scales of the Adjective Checkist (all P < 0.01), and 5 scales (physical functioning, role limitations due to physical health, social functioning, mental health, and vitality) of the SF-36 Health Survey (all P < 0.01). Topiramate was well tolerated and seems to be effective and safe in the long-term treatment of olanzapine-related adiposity in women. Furthermore, positive changes in the patients' state of health, psychological impairments, and health-related quality of life could be also observed. PMID- 17873680 TI - Early recognition of clozapine-induced myocarditis. AB - Recently, there has been an increased recognition of the association of clozapine with myocarditis and myocardiopathy. Commonly used diagnostic tests have very limited sensitivity in diagnosing this potentially life-threatening complication. We present 3 case reports of clozapine-induced myocarditis/cardiomyopathy that illustrate the development of a combined approach involving a clinical questionnaire and diagnostic testing at our hospital. This combination approach helped in the early recognition and successful treatment of clozapine myocarditis in one of our patients. Given the increasing recognition of this adverse reaction, we felt it timely to report our experience in diagnosing and treating this clinical syndrome. PMID- 17873681 TI - Does serotonin augmentation have any effect on cognition and activities of daily living in Alzheimer's dementia? A double-blind, placebo-controlled clinical trial. AB - OBJECTIVE: Recent studies suggest that cholinergic dysfunction does not provide a complete account of age-related cognitive deficits, and other neuronal systems like monoaminergic hypofunction are involved. In several studies, selective serotonin reuptake inhibitors demonstrated promotion in neurogenesis in the hippocampus and enhanced memory and cognition. The aim of this study is to survey the effect of serotonin augmentation on cognition and activities of daily living in patients with Alzheimer's disease. METHOD: The trial was designed as a 12-week randomized, placebo-controlled, double-blind study. One hundred twenty-two patients aged 55 to 85 years with mild-to-moderate Alzheimer's dementia were randomly allocated in 1 of the 3 treatment groups: fluoxetine plus rivastigmine, rivastigmine alone, or placebo group. Efficacy measures comprised assessments of cognition, activities of daily living, and global functioning. Hamilton Depression Scale also was used to assess changes in mood throughout the study. RESULT: Fluoxetine plus rivastigmine and rivastigmine groups demonstrated improvement on measures of cognitive and memory without any significant difference; however, the former group did better in their activities of daily living and global functioning. Patients taking placebo had significant deterioration in all the efficacy measures. Patients taking rivastigmine or rivastigmine plus fluoxetine had improvements in Hamilton Depression Scale without significant differences. CONCLUSIONS: Concomitant use of selective serotonin-enhancing agents and acetyl cholinesterase inhibitors can provide greater benefit in activities of daily living and global functioning in patients with cognitive impairment. Because our study is preliminary, larger double-blind studies are needed to confirm the results. PMID- 17873682 TI - A functional magnetic resonance imaging study of the effects of low frequency right prefrontal transcranial magnetic stimulation in depression. AB - The study aimed to explore the biological effects of low-frequency repetitive transcranial magnetic stimulation (LFR-TMS) treatment applied to the right prefrontal cortex, comparing this with the effects of high-frequency left-sided (HFL-TMS) in patients with treatment-resistant depression. Twenty-six patients with treatment-resistant depression were randomized to receive either daily LFR TMS or HFL-TMS treatment for 3 weeks and underwent functional magnetic resonance imaging during a planning task before and after treatment. Patients responded clinically to both forms of treatment with no difference in the degree of response (F1,24 = 0.65;P > 0.05). Low-frequency repetitive transcranial magnetic stimulation resulted in no overall change in task-related activation. However, responders to LFR-TMS demonstrated a bilateral decrease in activity in middle frontal gyrus. In contrast, HFL-TMS produced an increase in activation in left precuneus with responders showing increased activation in several additional regions. Response to LFR-TMS is associated with a bilateral reduction in frontal activation that does not seem to be a nonspecific effect of treatment and differs from the response to HFL-TMS. PMID- 17873683 TI - Cortical inhibitory dysfunction in bipolar disorder: a study using transcranial magnetic stimulation. AB - OBJECTIVE: Neuroanatomic evidence suggests that patients with bipolar disorder (BD) have impaired cortical inhibition (CI). However, there is little in vivo neurophysiological evidence supporting the occurrence of such impairments in this disorder. Using 3 transcranial magnetic stimulation paradigms, known as short interval CI (SICI), cortical silent period (SP), and interhemispheric inhibition (IHI), the authors measured inhibition in the motor cortex. METHOD: Fifteen patients with BD and 15 healthy subjects were enrolled. Short-interval CI involves stimulating with a subthreshold pulse a few milliseconds before a suprathreshold pulse, thereby inhibiting the size of the motor-evoked potential (MEP) produced by the suprathreshold pulse. In the SP paradigm, inhibition is reflected by the SP duration (ie, the duration of electromyographic activity cessation following a transcranial magnetic stimulation-induced MEP). Interhemispheric inhibition involves a subthreshold conditioning stimulus applied to the right motor cortex several milliseconds before a suprathreshold test stimulus is applied to the left motor cortex which inhibits the size of the MEP produced by the test stimulus by 50% to 75%. RESULTS: Patients with BD demonstrated deficits in all 3 paradigms: SICI (F1,28 = 5.55, P = 0.03; Cohen d = 0.86), SP (F1,28 = 5.24, P = 0.03; Cohen d = 0.84), and IHI (F1,28 = 3.41, P = 0.02; Cohen d = 0.77) compared with healthy volunteers with a large effect size. CONCLUSIONS: Our study supports the hypothesis that CI is decreased in BD. Further understanding of the neurophysiology of such deficiencies may help to elucidate future treatment options. PMID- 17873684 TI - A randomized, placebo-controlled trial of citicoline add-on therapy in outpatients with bipolar disorder and cocaine dependence. AB - INTRODUCTION: Bipolar disorder is associated with the highest rates of substance abuse of any psychiatric disorder. Cocaine use is particularly common in patients with bipolar disorder. Both cocaine use and bipolar disorder are associated with mood symptoms and cognitive impairment. Therefore, treatments that stabilize mood, improve cognition, and reduce cocaine use would be useful. Citicoline modulates phospholipids metabolism and neurotransmitter levels and appears to improve cognition in some central nervous system disorders. A 12-week, randomized, placebo-controlled, parallel-group, add-on, proof-of-concept trial of citicoline was conducted in 44 outpatients with a history of mania or hypomania and cocaine dependence. The primary aim was to examine memory, but mood and cocaine use were also assessed. METHOD: Participants were evaluated with a structured diagnostic interview; Inventory of Depressive Symptomatology-Self Report, Young Mania Rating Scale, and Rey Auditory Verbal Learning Test. Cocaine use was assessed with urine drug screens. Data were analyzed using mixed-model analysis of covariance, generalized estimating equations, and logistic regression analyses that used all of the available data. RESULTS: A significant group effect (P = 0.006) favoring citicoline was observed on the Rey Auditory Verbal Learning Test alternative word list. No significant between-group differences were found on the Inventory of Depressive Symptomatology-Self-Report or Young Mania Rating Scale. The citicoline group had a significantly lower probability of a cocaine positive urine at exit (P = 0.026). The covariate-adjusted odds ratio estimate was 6.41, suggesting that those who took placebo had 6.41-times higher odds of testing positive for cocaine at exit than those who took citicoline. Citicoline was well tolerated, with no participants to our knowledge discontinuing because of medication side effects. CONCLUSIONS: The use of citicoline was associated with improvement relative to placebo in some aspects of declarative memory and cocaine use, but not mood. The findings are promising and suggest that larger trials of citicoline are warranted. PMID- 17873685 TI - Suicides by violent means in individuals taking SSRIs and other antidepressants: a postmortem study in Sweden, 1992-2004. AB - A number of reports have linked consumption of selective serotonin reuptake inhibitors (SSRIs) with suicide by violent methods. We aimed to determine whether suicides with postmortem evidence of SSRI consumption are more likely to have used violent methods compared with suicides with no detectable antidepressants. Blood samples from all suicides in Sweden during 1992-2004 were examined. Suicides were classified into those who died by violence and nonviolent (self poisoning) methods using information from police records and autopsy. In addition, we investigated proportions of violent suicide in individuals who died with detectable levels of tricyclic and other antidepressants. The sample consisted of 14,691 suicides. Of the 1958 suicides with detectable levels of SSRIs, 1247 were by violent means (63.7%) compared with 7835 of 11,045 suicides (70.9%) in antidepressant-free group (chi2(1) = 7.6; P < 0.01). [corrected] When subdivided by gender and age-bands, we found specific groups with significantly lower proportions of violent suicides compared with the antidepressants-free group, including men aged 15-24 years. PMID- 17873686 TI - Efficacy of extended-release naltrexone in alcohol-dependent patients who are abstinent before treatment. AB - Extended-release naltrexone (XR-NTX) is a once-a-month injectable formulation that is Food and Drug Administration-approved for the treatment of alcohol dependence in patients able to abstain from alcohol before treatment initiation. This paper presents the results of an analysis of efficacy data from a subgroup of patients with 4 days or more of voluntary abstinence before treatment initiation (n = 82) on a wide range of drinking-related outcomes. In these patients, all of whom received counseling, the rate of abstinence was severalfold higher for XR-NTX 380 mg compared with placebo: median time to first drink was 41 days versus 12 days, respectively; rate of continuous abstinence at end of the study was 32% versus 11% (P = 0.02). Extended-release naltrexone 380 mg, compared with placebo, substantially increased time to first heavy drinking event (>180 days vs 20 days; P = 0.04) and decreased the median number of any drinking days per month by 90% (0.7 vs 7.2; P = 0.005) and heavy drinking days per month by 93% (0.2 days vs 2.9 days; P = 0.007). The XR-NTX 380 mg group also had more than twice as many responders compared with placebo (70% vs 30%; P = 0.006; responder defined as having no more than 2 heavy drinking days in any consecutive 28-day period) and experienced greater improvement in gamma-glutamyl transpeptidase levels (P = 0.03). Outcomes for XR-NTX 190 mg (n = 26) were generally intermediate, demonstrating a dose-response effect. In conclusion, XR-NTX 380 mg prolonged abstinence and reduced the number of heavy drinking days and drinking days in patients who were abstinent for as few as 4 days before treatment initiation. PMID- 17873687 TI - High-dose ziprasidone in treatment-resistant schizophrenia and affective spectrum disorders: a case series. PMID- 17873688 TI - Clozapine and amisulpride in refractory schizophrenia and alcohol dependence. PMID- 17873689 TI - Aripiprazole improves metabolic adversity in olanzapine-treated schizophrenic patients. PMID- 17873690 TI - Acute urinary retention associated with selective serotonin reuptake inhibitors and ziprasidone. PMID- 17873691 TI - Aripiprazole for relapse prevention and craving in alcohol-dependent subjects: results from a pilot study. PMID- 17873692 TI - Neuroreceptor gene polymorphisms and olanzapine depressive symptom response in schizophrenia. PMID- 17873693 TI - Significant elevations of prolactin levels in patients who shifted from conventional depot antipsychotics to long-acting risperidone. PMID- 17873694 TI - Resolution of haloperidol-induced hyperprolactinemia with aripiprazole. PMID- 17873695 TI - Resolution of tardive dyskinesia after addition of aripiprazole to haloperidol depot. PMID- 17873696 TI - Quetiapine as treatment for delirium during weaning from ventilation: a case report. PMID- 17873697 TI - Unfavorable smell with citalopram? PMID- 17873698 TI - Comments on "neurological soft signs in schizophrenic patients treated with conventional and atypical antipsychotics". PMID- 17873699 TI - Intravenous valproate treatment of uncontrollable aggression: a case report. PMID- 17873700 TI - Evidence-based guidelines for interpretation of the Hamilton Rating Scale for Depression. PMID- 17873701 TI - Are the effects of rater training sustainable? Results from a multicenter clinical trial. PMID- 17873702 TI - Comments on "Why do clinical trials fail? The problem of measurement error in clinical trials: time to test new paradigms?". PMID- 17873703 TI - Pregabalin in patients with antidepressant treatment-resistant somatoform disorders: a case series. PMID- 17873704 TI - GABAergic medications for treating alcohol dependence. PMID- 17873706 TI - Megadose clonazepam dependence: a case report. PMID- 17873707 TI - Perceptual disturbances associated with low-dose bupropion sustained-release treatment. PMID- 17873708 TI - Long-term lithium treatment and survival from external causes including suicide. PMID- 17873711 TI - Depressive symptomatology, medication persistence, and associated healthcare costs in older adults with glaucoma. AB - PURPOSE: Depressive symptoms may impact patients' medication use behavior and utilization of healthcare services. This study examined association between depressive symptoms and Glaucoma medication-related persistence and predictors of associated healthcare charges in older adults with primary open angle Glaucoma. METHODS: This study used a retrospective cohort of older adults with primary open angle Glaucoma who completed health status assessment, used Glaucoma medications, and were enrolled in a Medicare Health Maintenance Organization. Baseline assessment surveyed patients on demographics, healthcare service utilization in year before enrollment, lifestyle, and quality of life. Demographic, clinical, and utilization-related economic variables were retrieved from administrative claims database of patients' Health Maintenance Organization. Survival techniques were used to measure time to discontinuation (persistence) and Center for Epidemiologic Studies Depression Scale a 20-item self-reporting scale assessed depressive symptomatology on a range of 0 to 60. Associations were examined using mixed-model regression approach. Sensitivity analysis that considered log transformed and untransformed specifications of cost variable tested model appropriateness. RESULTS: In total 268 patients were followed for 2 years (N=536). After controlling for potential confounders and temporal effects, depressive symptomatology was associated with decreased Glaucoma medication related persistence (P<0.005). Patients who lived alone and had cardiovascular disease showed higher odds of experiencing depressive symptoms (P<0.005). Healthcare charges increased with number of comorbidities and prescriptions (P<0.005). CONCLUSIONS: Presence of depressive symptoms in patients lead to poor Glaucoma medication use behavior. Healthcare expenditures increased for patients with increase in comorbidities. Plan enrollees' risk assessment offers advantage of improving health outcomes and reduces healthcare utilization. PMID- 17873709 TI - Increase in plasma concentration of amisulpride after addition of concomitant lithium. PMID- 17873712 TI - Amniotic membrane transplantation for intraoperative conjunctival repair during trabeculectomy with mitomycin C. AB - PURPOSE: To describe the use of amniotic membrane (AM) transplantation for the repair of conjunctival buttonholes during trabeculectomy with mitomycin C. METHODS: Four eyes of 3 patients with thin conjunctiva, precluding watertight conjunctival closure at the incision site with suturing, underwent intraoperative AM grafts over the leaking areas. RESULTS: In all eyes, a functional, nonleaking bleb was achieved. At the latest follow-up (8 to 30 mo), all eyes had intraocular pressures of 12 mm Hg or less without medications. CONCLUSIONS: AM transplantation was effective in the intraoperative closure of conjunctival buttonholes which developed at the incision line in 4 eyes. This intervention may be a useful addition to the glaucoma surgeon's repertoire of surgical techniques. PMID- 17873713 TI - One-site versus two-site endoscopic cyclophotocoagulation. AB - PURPOSE: To report the intraocular pressure (IOP) lowering effect of endoscopic cyclophotocoagulation (ECP) treatment through 1 versus 2 corneal incisions. METHODS: This is a retrospective consecutive case review of combined ECP and phacoemulsification (PE). Group 1 included patients undergoing PE-ECP through 1 clear cornea incision and group 2 involved PE followed by ECP through 2 incisions. The 1 versus 2 site selection was performed in a nonrandomized fashion at the time of surgery. Data including age, sex, preoperative diagnosis, number of preoperative and postoperative glaucoma medications, complications, treatment failures, and IOP were collected and analyzed using analysis of variance and t tests where appropriate. RESULTS: Group 1 included 15 patients and group 2 included 25 patients. Age of patients in group 1 (66.07+/-17.73) and group 2 (73.48+/-11.31) were similar (P=0.11). Visual acuity in group 1 ranged from 20/40 to 20/400 and from 20/40 to counting fingers in group 2. The preoperative diagnoses were similar between the 2 groups. Preoperative IOP was 23.60+/-3.89 in group 1 and 24.48+/-8.99 in group 2 (P=0.72). IOP decreased in group 1 from 23.60+/-3.89 to 17.93+/-4.38 (P=0.0008) and in group 2 from 24.48+/-8.99 to 13.88+/-3.22 (P=0.00001) with 3 months of follow-up. IOP at 3 months was significantly lower in group 2 compared with group 1 (P=0.002). Six-month IOP data for group 1 (16.00+/-2.77) and group 2 (13.00+/-3.09) remained statistically significant in favor of 2-site PE-ECP (P=0.04). Glaucoma medication use decreased more in group 2 (2.56+/-0.71 to 0.52+/-0.59) versus group 1 (2.47+/-0.74 to 1.93+/-0.88) (P=0.00001). CONCLUSIONS: Two-site PE-ECP may result in statistically significant IOP lowering and less dependence on glaucoma medications compared with single site PE-ECP. PMID- 17873715 TI - Interocular differences in optic nerve head topography of the subjects with unilateral peripapillary myelinated nerve fibers. AB - PURPOSE: To determine the interocular differences in optic nerve head topography of the subjects with unilateral peripapillary myelinated nerve fibers. MATERIALS AND METHODS: A total of 21 healthy subjects with unilateral peripapillary myelinated nerve fibers were included into the study. Patients had no ocular disease except refractive disorders. Optic nerve head topographic analyses of both eyes of each subject were performed using a confocal scanning laser ophthalmoscope, HRT-II (Heidelberg Retina Tomography II, version 1.6). The disc area, topography standard deviation, and a total of 12 topographic parameters were calculated by the HRT-II. RESULTS: The mean age of the subjects was 28.3+/ 3.4 years. The mean refractive error of the eyes with and without myelinated nerve fibers were -3.56+/-1.73 D and -0.98+/-0.66 D, respectively (P<0.05). There were no significant interocular differences in the disc area of the eyes with and without peripapillary myelinated nerve fibers (P>0.05). Eyes with peripapillary myelinated nerve fibers were found to have significantly less "neuroretinal rim area" and "neuroretinal rim area-to-disc area ratio" than those eyes with no myelination (P<0.05 for both). All other parameters were found not to reveal any significant interocular differences (P>0.05 for all of them). Sectorial analysis of the parameters including neuroretinal rim area and neuroretinal rim area-to disc area ratio did not reveal any significant differences between the groups (P>0.05). CONCLUSIONS: Neuroretinal rim area and rim area-to-disc area ratio of the eyes with peripapillary myelinated nerve fibers were found to be significantly less than that of the fellow eyes with no myelination. This should be taken into consideration when monitoring glaucoma suspects with peripapillary myelinated nerve fibers. PMID- 17873714 TI - A pilot study to detect glaucoma with confocal scanning laser ophthalmoscopy compared with nonmydriatic stereoscopic photography in a community health screening. AB - PURPOSE: To assess the efficacy and practical usefulness of the Heidelberg Retina Tomograph II (HRT II) compared with nonmydriatic stereoscopic photography in a public glaucoma screening. METHODS: We examined 1173 local residents, aged 40 years or older, who visited a community health screening in Komatsu City. Initial glaucoma screening consisted of noncontact pneumotonometry, nonmydriatic stereoscopic fundus photography, and HRT II. When glaucoma was suspected, the subjects were referred for a definitive examination, in which slit-lamp biomicroscopic examination, Goldmann applanation tonometry, Humphrey 30-2 test, gonioscopy, and optic nerve head evaluation were performed. RESULTS: A total of 97.2% (2279/2345) of the nonmydriatic stereoscopic optic disc photographs could be interpreted and 93.4% (2189/2345) were good images. HRT II measurements were successful in 99.0% (2322/2345) of eyes, and acceptable images were obtained in 91.9% (2154/2345) of eyes. On the basis of clinical diagnoses, 94 eyes of 60 participants were diagnosed with glaucoma. The sensitivity of nonmydriatic stereoscopic photographs for personal-level analysis and eye-level analysis was 95.8% and 95.5%, respectively. Using Moorfield's regression analysis, HRT sensitivity and specificity were 72.3% to 91.5% and 84.0% to 93.1%, respectively, for personal-level analysis, and 60.3% to 72.6% and 89.7% to 95.6%, respectively, for eye-level analysis. CONCLUSION: Although HRT II did not detect glaucoma as well as optic nerve stereophotographs in this Japanese population, it may play a role in community health screening. PMID- 17873716 TI - Application of shape-based analysis methods to OCT retinal nerve fiber layer data in glaucoma. AB - PURPOSE: (1) To evaluate the performance of shape-based analysis [wavelet-Fourier analysis (WFA) and fast Fourier analysis (FFA)] applied to retinal nerve fiber layer (RNFL) thickness values obtained from the optical coherence tomograph (OCT) to discriminate healthy and glaucomatous eyes. (2) To compare the performance of the shape-based metrics to that of the standard OCT output measures (Inferior Average and Average Thickness). METHODS: RNFL values were obtained from 152 eyes of 152 individuals (83 healthy and 69 "mild"-stage perimetric glaucoma). WFA and FFA were performed on the RNFL values and linear discriminant functions for both were obtained using Fisher linear discriminant analysis. Performance was evaluated by calculating sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (ROC area). RESULTS: The ROC area of the shape-based methods [0.94 (WFA) and 0.88 (FFA)] was greater than that of OCT metrics [0.81 (Inferior Average) and 0.74 (Average Thickness)]. Specifically, WFAs performance was significantly better than both the FFA (P=0.009) and the Inferior Average (P=0.001). Inferior average performed significantly better than Average Thickness (P=0.006). CONCLUSIONS: The ability to differentiate glaucomatous from healthy eyes using stratus OCT measurements is improved by using these analysis methods that emphasize the shape of the RNFL thickness pattern. PMID- 17873717 TI - Targeting relatives of patients with primary open angle glaucoma: the help the family glaucoma project. AB - PURPOSE: To assess the knowledge of patients with open angle glaucoma (OAG) and their family members about OAG risk factors and to study the referral of family members for eye examinations. DESIGN: Cross-sectional survey and prospective cohort study. METHODS: We interviewed OAG patients (probands) at the Wilmer Eye Institute and their biologically related parents, siblings, and children about their knowledge of OAG risk factors. Qualified family members were offered an eye examination through the EyeCare America program. Three months after initial contact, a follow-up telephone questionnaire determined the outcome of the referral. RESULTS: Among 102 probands and 100 (of 230 eligible) family members who were interviewed, there was high awareness that OAG is related to older age (85% both groups). More probands knew of the association with higher intraocular pressure (95%) compared with family (78%). Yet, 21% of both groups were not aware that OAG is hereditary, and only 53% of probands and 30% of family members knew that OAG is more common in certain ethnic groups. Only two-thirds of probands had suggested that family members have an eye examination. Eighty percent of family members had had an eye examination within the last year; of 21 with no recent examination, 66% (13/21) accepted referral. CONCLUSIONS: The Help the Family Glaucoma project developed a novel approach to identify those at high-risk for OAG. Screening of relatives of OAG patients deserves further study in a more representative selection of the general population. PMID- 17873718 TI - The acute morphologic changes that occur at the optic nerve head induced by medical reduction of intraocular pressure. AB - PURPOSE: The mechanical theory of glaucoma postulates that raised intraocular pressure (IOP) causes laminar distortion resulting in damage to axons at the optic nerve head. There is some evidence that the change in morphology may occur over a short time course. The aim of this paper was to detail the acute morphologic changes at the optic nerve head when IOP was lowered with medical therapy in a clinical population. METHODS: Subjects referred to the glaucoma clinic that had a documented IOP of over 28 mm Hg, on no treatment, in one or both eyes were included. Tonometry, pachymetry, and scanning laser ophthalmoscopy were performed before and after lowering IOP with topical apraclonidine and oral acetazolamide. The significance of change in outcome variables was assessed using a paired t test allowing for dependence within subjects and, for sensitivity, with a nonparametric Wilcoxon signed-rank test. RESULTS: Data were obtained from 38 eyes of 19 patients with a mean age of 67 years. After lowering IOP for only 1 hour, there was a significant decrease in mean cup volume (mean change in volume below surface 26.8 microm3, P< or =0.001) and mean cup depth (13.8 microm, P<0.01), there being a corresponding increase in mean rim area (37.3 microm2, P<0.034). There was no statistically significant change in central corneal thickness after administration of the IOP lowering medications. CONCLUSIONS: In the present study, it was shown that acute and statistically significant alterations in optic disc morphology occur when IOP is lowered medically with a combination of topical apraclonidine and systemic acetazolamide. The technique, therefore, may be useful to further investigate subgroups of glaucomatous eyes and test etiologic hypotheses. PMID- 17873719 TI - Cataract surgery after needling revision of trabeculectomy blebs. AB - PURPOSE: To assess the effect of cataract surgery on trabeculectomy blebs that have previously had successful needling revision. STUDY DESIGN: A retrospective controlled study. PATIENTS AND METHODS: A cohort of patients undergoing needling of a poorly functioning trabeculectomy bleb was collected. From this cohort a group having had a successful needling outcome who subsequently underwent uneventful phacoemulsification was identified. Each member of this phacoemulsification group was matched with 2 controls from the cohort who had also had success from needling but who had not undergone cataract surgery. Survival analysis was performed using the date of cataract surgery as the entry time for the phacoemulsification group. For controls the entry time was the date of needling adjusted by subtracting the time between needling and cataract surgery of the matched phacoemulsification group subject. In this way an identical period had elapsed between needling and entry time for both phacoemulsification group and controls. Survival depended on (a) intraocular pressure (IOP) < or =21 mm Hg and (b) IOP <80% of preneedling IOP, on the same or fewer glaucoma drops and without further glaucoma surgery. RESULTS: Forty-five patients were included. Intervals from trabeculectomy to needling, needling to phacoemulsification, and from phacoemulsification to final follow-up ranged from 1 to 320, 4 to 15, and 5 to 19 months, respectively. Mean survival for the phacoemulsification group was 34.4 weeks and 190.0 for controls [hazard ratio 8.1 (95% confidence interval: 2.8-23.9) (log rank P<0.0001)]. Survival at final follow-up was 4/15 and 25/30 for cases and controls, respectively (chi2 P=0.0002). CONCLUSIONS: Previously successful bleb needling can be significantly compromised by subsequent cataract surgery. PMID- 17873720 TI - Erythropoietin: a candidate neuroprotective agent in the treatment of glaucoma. AB - Glaucoma is a progressive optic neuropathy that is the leading cause of irreversible blindness in the world. Although methods to lower intraocular pressure are the mainstay of glaucoma therapy, there are currently no available treatment modalities targeted at neuroprotection. Erythropoietin is a hematopoietic cytokine that has been shown to possess remarkable tissue protective properties in preclinical models of neurodegeneration. As a result, there is a growing interest to explore the neuroprotective properties of erythropoietin as a possible therapeutic agent in neuropathic diseases of the eye such as glaucoma. Initial results in animal models have been promising, but further studies are needed to fully evaluate the safety and efficacy of this candidate neuroprotective agent in clinical trials. PMID- 17873721 TI - Gray optic disc crescent: influence of ethnicity in a glaucoma population. AB - PURPOSE: To evaluate the prevalence of the gray optic disc crescent within a glaucoma population and the influence of ethnicity and other variables. PATIENTS AND METHODS: Consecutive patients of white or African American ethnicity, seen in the Glaucoma Service of Yale Eye Center, were included in the study. The 2 ethnic groups were not matched for refractive error, age, or stage of glaucoma. Stereodisc photos, suitable for detailed evaluation of disc and parapapillary features, of 1 or both eyes were selected by 1 investigator. The photos were masked to the other 2 investigators, who independently interpreted the disc and parapapillary features. The prevalence of the gray crescent in the 2 ethnic groups was compared by chi analysis. Correlation with age, sex, refractive error, intraocular pressure, and the presence and degree of glaucomatous optic neuropathy were also analyzed. RESULTS: Of 225 patients (447 eyes), the gray crescent was seen in one or both eyes of 32 patients (14.2%), which included 21 of the 77 [27.3%, 95% confidence intervals (CI) 9.95] African Americans and 11 of the 148 (7.4%, 95% CI 4.23) whites. The difference in prevalence of the gray crescent between the 2 ethnic groups was significant (P<0.0001). The prevalence of the gray crescent did not correlate with age, sex, refractive error, intraocular pressure or the presence or degree of glaucomatous optic neuropathy. CONCLUSIONS: The gray optic disc crescent is a common finding within a glaucoma population, especially among persons of African heritage, but does not correlate with the presence or degree of glaucomatous optic neuropathy nor other patient variables. PMID- 17873722 TI - Management of suprachoroidal hemorrhage. PMID- 17873723 TI - Improving the complex nature of care transitions. PMID- 17873724 TI - The Johns Hopkins Fall Risk Assessment Tool: postimplementation evaluation. PMID- 17873725 TI - No safety, no quality: synthesis of research on hospital and patient safety (1996 2007). AB - The aim of this study was to identify associated research trends in patient safety and hospitals. Content analyses were used to analyze the titles and abstracts of journal articles included in the PubMed database (1996-March 2007; n = 6569). The given category code for each record was analyzed. The developed consensus system may help scholars and clinicians identify studies to be done, examine trends in the research on hospital safety, and advance the knowledge in this field. PMID- 17873726 TI - Implementation and outcomes of a rapid response team. AB - Adverse events in hospitalized patients are preceded by clinical signs of decline. Thus, early recognition and intervention should improve patient outcomes. At the University of Kentucky Hospital, the impetus to start a rapid response team (RRT) was to decrease unplanned admissions to ICU, adverse events, and mortality overall. On the basis of the outcomes at our hospital, we conclude that there is benefit to having an RRT. The following article outlines processes for RRT implementation and our outcomes to date. PMID- 17873728 TI - Impact of oral hygiene on prevention of ventilator-associated pneumonia in neuroscience patients. AB - Ventilator-associated pneumonia is one of the most frequent complications among critically ill patients. Growth of pathogenic bacteria in dental plaque may serve as the source of these infections. This performance improvement initiative evaluated an aggressive oral care approach to prevent the accumulation of plaque containing bacteria. Our data support the use of these oral care measures and deep oral-pharyngeal suctioning for the prevention of aspiration of oral contents. PMID- 17873729 TI - Nurses improve medication safety with medication allergy and adverse drug reports. AB - Medicine-related illnesses cost more than 75 billion dollars annually. Adverse drug reactions (ADRs) are the fourth to sixth leading causes of death in the United States. An educational campaign to reduce ADRs and improve documentation included (1) an allergy awareness campaign, (2) staff nurses' training on documentation of allergies/ADRs, (3) patient-oriented brochures to encourage allergy reporting and ADRs, and (4) a fact sheet about ADRs. As a result, the documentation of medication allergies and ADRs improved significantly in our organization. PMID- 17873730 TI - Including the provider in the assessment of quality care: development and testing of the Nurses' Assessment of Quality Scale - acute care version. AB - This study was designed to develop a psychometrically sound measure of nurses' evaluation of patient care delivered. The Nurses' Assessment of Quality Scale Acute Care Version (NAQS-ACV), derived from the qualitative interviews of acute care nurses, was initially 138 items formatted as a Likert-type scale and administered to 1272 nurses from 7 acute care hospitals. After analysis, the scale was reduced to 77 items contained in 8 factors. Reliability estimates for the factors ranged from 74 to 94. PMID- 17873731 TI - Nurses' perceptions of their work environment. AB - Supervisor support is one factor contributing to a healthy work environment for registered nurses (RNs). This study explored differences in RNs' perceptions of their work environment by both years in the profession and current position. A statistically significant difference was found for RNs' perceptions of Supervisor Support based on number of years in current position. Those RNs with less than 2 years in their current position perceived the greatest Supervisor Support (X = 6.96; P = .03). PMID- 17873732 TI - Strategies to accelerate translation of research into primary care within practices using electronic medical records. AB - This research describes implementation strategies used by primary care practices using electronic medical records in a national quality improvement demonstration project, Accelerating Translation of Research into Practice, conducted within the Practice Partner Research Network. Qualitative methods enabled identification of strategies to improve 36 quality indicators. Quantitative survey results provide mean scores reflecting the integration of these strategies by practices. Nursing staff plays important roles to facilitate quality improvement within collaborative primary care practices. PMID- 17873733 TI - How grounded theory can improve nursing care quality. AB - This article presents an overview of the grounded theory research method and demonstrates how nurses can employ specific grounded theories to improve patient care quality. Because grounded theory is derived from real-world experience, it is a particularly appropriate method for nursing research. An overview of the method and language of grounded theory provides a background for nurses as they read grounded theories and apply newly acquired understandings to predictable processes and patterns of behavior. This article presents 2 exemplar grounded theories with suggestions as to how nurses can apply these and other grounded theories to improve the provision of quality nursing care. PMID- 17873734 TI - Influence of personality on care quality of hospital nurses. AB - This study investigates the relationship between hospital nurse personality and care quality in Taiwan. Hierarchical regression analysis was applied to data for 192 pairs of nurses and patients. Analytical results are as follows: (1) nurse openness was positively correlated with patient perceptions of responsiveness and (2) nurse neuroticism was negatively correlated with patient perceptions of responsiveness, assurance, and empathy. PMID- 17873735 TI - Do organizational factors explain the quality of care? AB - This study investigated the perceptions of patients, nurses, physicians, and managers of the quality of care. While they all evaluated the quality of care to be good, the evaluations of patients and staff were different from each other's. Organizational factors such as values and work explained the quality of care evaluated by nursing staff and physicians compared to work and leadership by managers. No obvious relationship between quality and leadership could be found. PMID- 17873736 TI - Assessing quality of nursing care as a confounding variable in an outcome study on neurodevelopmental treatment. AB - When planning a study measuring the effects of a neurodevelopmental treatment (NDT), we were confronted with the methodological problem that while measuring the effects of NDT, a rival hypothesis is that the decision to implement the NDT might be related to the quality of nursing care. Therefore, we measured the quality of nursing care as a possible confounding variable in relation to this outcome study. The quality of nursing care was measured on 12 wards participating in the experimental and control groups of the outcome study. Data were collected from 125 patients and 71 nurses and patients' records. The findings showed no significant differences in the quality of nursing care between the 2 groups of wards (P = .49). This method may be useful to other researchers conducting outcome research and who are confronted with a similar methodological problem. PMID- 17873737 TI - Colonic polyp as lead point for intussusception. PMID- 17873738 TI - Eosinophilic oesophagitis: epidemiology, clinical aspects, and association to allergy. AB - Eosinophilic oesophagitis is characterised by age-dependent symptoms mimicking gastrooesophageal reflux disease, a distinct endoscopic appearance and a histological picture with extensive infiltration of eosinophils in the oesophageal mucosa. Eosinophilic oesophagitis is more frequently seen in males, and patients often belong to the paediatric or adolescence age groups. The exact prevalence of eosinophilic oesophagitis is unknown, but it has been suggested that the United States has a higher prevalence than Europe. Several treatment algorithms have been suggested, including elemental diets, oral steroids, inhaled (swallowed) steroids, and leucotriene receptor antagonists. Detailed information on the eosinophilic inflammatory processes in the oesophageal mucosa was initially obtained from animal models, in particular with regard to the role of interleukin-5 and the chemokine eotaxin-1 in eosinophilic recruitment. Studies have suggested a cytotoxic effect of eosinophilic degranulation products on nerve fibers in the gastric/intestinal mucosa, implicating a direct effect of allergic inflammation on gastrointestinal motility. Human studies recently have emphasized the role of eotaxin-3 and identified a single nucleotide polymorphism probably related to disease susceptibility. PMID- 17873739 TI - Subclinical neurological involvement in treated celiac disease: the dark side of gluten-related encephalopathies. PMID- 17873740 TI - Natural history of antibodies to deamidated gliadin peptides and transglutaminase in early childhood celiac disease. AB - INTRODUCTION: Gliadin proteins play a key role in the pathogenesis of celiac disease; however, as a screen for celiac disease, anti-gliadin antibody testing has been replaced by the more sensitive and specific serological assays for transglutaminase autoantibodies (TGAA). A new generation of anti-gliadin antibody assays has been developed to detect synthetic, deamidated homologous gliadin peptides (DGP) with high sensitivity and specificity. METHODS: Sera were collected prospectively from children with an increased risk for celiac disease as part of an ongoing study at Denver, and studied for the development of celiac autoimmunity. We investigated the high-performance DGP antibody assay in 50 TGAA positive children both before the development of celiac autoimmunity and following the institution of a gluten-free diet to determine the relationship of DGP antibodies to TGAA. TGAA were measured by an in-house radioassay. RESULTS: DGP antibodies and TGAA parallel each other over the period of years children were studied. DGP antibodies resolved sooner than TGAA in subjects on a gluten free diet. DGP antibodies appeared earlier than TGAA in 9 children. CONCLUSIONS: Measuring DGP antibodies may be more useful than TGAA in monitoring children on a gluten-free diet. DGP antibodies can precede the appearance of TGAA in some at risk children. PMID- 17873741 TI - Increased interleukin-10 in Helicobacter pylori infection could be involved in the mechanism protecting from allergy. AB - BACKGROUND: A protective effect of Helicobacter pylori infection against allergic diseases has been reported. The increasing incidence of childhood allergy in developed countries may be a result of reduced stimulation of the immune system by early chronic infections, with the protective effect of gastrointestinal microbes being mediated by regulatory T lymphocytes and production of interleukin (IL)-10. To elucidate a possible mechanism involved in protecting against the development of atopy, we measured expression of IL-10 in gastric mucosa of children with H pylori gastritis. PATIENTS AND METHODS: Gastric biopsies were performed during endoscopy in 48 children (median age, 9 years), 32 of whom had H pylori gastritis and 16 of whom served as controls. Interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), and IL-10 were measured in tissue homogenate by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The amounts of IFN-gamma, IL-1beta, and IL-10 transcripts were quantified via competitive RT-PCR with use of dilution series of specific competitors. RESULTS: Expression of IFN-gamma and IL-10 were significantly higher in H pylori-infected children. No direct correlation with age was found, but a further increase in IL 10 expression was found in H pylori-infected children older than 4 years, whereas in control subjects, IL-10 expression tended to be lower in older children. IL 1beta expression was similar in infected children and control subjects. In H pylori-infected children, the prevalence of allergy was significantly higher in children with lower cytokine expression in gastric mucosa. CONCLUSIONS: In children, H pylori-induced inflammatory response is associated with development of cell-mediated immunity of T-helper 1 type, as demonstrated by increased IFN gamma expression. The significantly increased expression of gastric IL-10 in H pylori-infected children and its further increase in older children suggest that this chronic infection may influence IL-10 production even beyond the age of 4 years. H pylori may be one of the infections with the potential to modulate immune responses. PMID- 17873742 TI - Oral tacrolimus for steroid-dependent and steroid-resistant ulcerative colitis in children. AB - PURPOSE: To evaluate tacrolimus in 3 situations: for the induction of remission in children with severe steroid-resistant ulcerative colitis (UC); for steroid sparing in children with steroid-dependent UC in whom treatment with other immunosuppressants fails; and for the maintenance of remission in children with steroid-dependent and steroid-resistant UC. PATIENTS AND METHODS: We retrospectively evaluated 18 consecutive patients (13 with pancolitis) who were treated with oral tacrolimus at our institution from May 1999 to October 2005. Nine patients had steroid-resistant UC and 9 patients were steroid-dependent. We started patients initially on tacrolimus 0.2 mg/kg divided twice daily, with a goal plasma trough level of 10 to 15 ng/mL for the first 2 weeks, and then titrated doses to achieve plasma levels between 7 and 12 ng/mL after induction. RESULTS: Of the 18 patients in this study, 17 showed a positive response to tacrolimus therapy (ie, cessation of diarrhea and other symptoms) and 5 showed a prolonged response to tacrolimus. The mean time from initiation of tacrolimus therapy until response was 8.5 days. The mean duration of response was 260 days. Eleven of 18 patients required colectomy, including all of the patients with steroid-resistant UC, but only 2 of 9 who were steroid-dependent. The mean time from initiation of tacrolimus until colectomy was 392 days. CONCLUSIONS: It is possible that tacrolimus may benefit selected patients with steroid-dependent UC, including those who are intolerant of 6-mercaptopurine or azathioprine. Conversely, patients with steroid-resistant UC are unlikely to sustain a prolonged clinical response to tacrolimus and seem to require colectomy eventually. Careful considerations of risk versus benefit, as well as close monitoring for adverse effects, are essential in all patients. PMID- 17873743 TI - Effect of long-term low-dose prednisone on height velocity and disease activity in pediatric and adolescent patients with Crohn disease. AB - OBJECTIVES: To determine whether long-term low-dose prednisone (LTLDP) therapy has a decelerating effect on growth velocity and whether this therapy is effective in the maintenance of remission in the subgroup of pediatric patients with Crohn disease (CD) who had previously experienced flares on more than 1 occasion when prednisone was discontinued. PATIENTS AND METHODS: A retrospective chart review of patients was done. Our sample consisted of patients 6 to 17 years of age with CD who had received uninterrupted prednisone at an average daily dose of 0.1 to 0.4 mg x kg(-1) x day(-1) for at least 8 weeks. Their heights were plotted on sex-appropriate growth charts at 4 time points: 1 year before LTLDP, at therapy onset, at therapy discontinuation, and 1 year after therapy was discontinued. The height velocities (HVs) were compared with the normal HV established by Tanner. The disease activities of 2 groups were compared: LTLDP plus azathioprine/6-mercaptopurine (AZA/6-MP) and LTLDP alone. RESULTS: One hundred two patients were included. The mean age of our sample was 13.7 +/- 2.7 years (standard deviation). The mean dose of prednisone dose was 0.18 +/- 0.07 mg x kg(-1) x day(-1)), for a mean duration of therapy of 14.4 +/- 7.2 months. Throughout the study, 78% of patients had normal HV. Growth deceleration was seen in 19% of patients with prior normal growth. Of this group, 31% had "catch-up" growth 1 year after prednisone was discontinued; the remaining 69% did not. Catch up growth was more likely in patients who had reached the expected age peak HV, which is defined as 12.5 years for girls and 13.5 years for boys (P = 0.04). In addition, 6 patients reached the peak HV after LTLDP discontinuation; 13 did not. We found no difference in the maintenance of remission rate between the compared groups. CONCLUSIONS: A minority of our study population had growth deceleration. Age was an important factor for subsequent catch-up growth. LTLDP efficacy to maintain remission was not different from that of LTLDP plus AZA/6-MP; differences in concomitant therapies (eg, antibiotics, infliximab) between the 2 groups were not statistically significant. PMID- 17873744 TI - Esophageal subepithelial fibrosis in children with eosinophilic esophagitis. AB - OBJECTIVES: Esophageal subepithelial fibrosis has been reported in adults with eosinophilic esophagitis (EE). Our goal was to determine the prevalence of esophageal fibrosis in children with EE, to determine whether it is specific for EE, and to correlate it with clinical and pathological features. PATIENTS AND METHODS: Twenty-one children with EE, 7 with eosinophilic gastroenteritis, 6 with gastroesophageal reflux disease, and 17 control children were studied. Distal esophageal biopsy specimens containing lamina propria were evaluated for extent of subepithelial collagen deposition by use of trichrome staining. Fibrosis was defined as abnormally increased collagen deposition, determined after the establishment of normal patterns on sections of esophagus from pediatric autopsies. Maximum numbers of intraepithelial and lamina propria eosinophils per high-power field by hematoxylin and eosin staining and mast cells per high-power field by immunohistochemical staining for tryptase were determined. Eosinophil and mast cell degranulation in epithelium and lamina propria was determined by use of immunohistochemical staining for major basic protein and tryptase, respectively. The patients' records were reviewed. RESULTS: Esophageal subepithelial fibrosis was present in 12 (57%) patients with EE, 1 with eosinophilic gastroenteritis, 0 with gastroesophageal reflux disease, and 1 control patient. Forty-two percent of those with fibrosis had dysphagia, 80% of whom had food impactions; these symptoms were present only in patients with fibrosis. Within the EE group, fibrosis was not associated with duration of symptoms or with increasing numbers of infiltrating eosinophils/mast cells, but it was associated with eosinophil degranulation. CONCLUSIONS: Esophageal subepithelial fibrosis is prevalent in EE and is specific for the disease in children. It is associated with dysphagia, and it may explain and predict future esophageal dysmotility. Fibrosis is related to the extent of esophageal eosinophil activation, as evidenced by eosinophil degranulation. PMID- 17873745 TI - Early stage of biliary atresia is associated with significant changes in 8 hydroxydeoxyguanosine and mitochondrial copy number. AB - OBJECTIVES: Oxidative stress is known to be involved in the pathogenesis of biliary atresia (BA), but the mechanism has yet to be elucidated. We studied 8 hydroxydeoxyguanosine (8-OHdG) and mitochondrial copy number as potential markers for oxidative stress in BA. METHODS: Hepatic immunoreactive 8-OHdG expression was investigated during the early stage of BA when the patients received Kasai portoenterostomy (KP), during the late stage when the patients received liver transplantation (LT), in patients with choledochal cyst as disease control, and in patients with histologically normal liver as normal control. Apoptosis of liver cells was examined by terminal deoxynucleotidyl transferase-mediated 2' deoxyuridine 5'-triphosphate-biotin nick end-labeling stain. The mitochondrial DNA copy number was measured by real-time polymerase chain reaction. RESULTS: The number of hepatocytes positive for immunoreactive 8-OHdG was significantly increased in KP (65% +/- 18%) compared with LT (30% +/- 32%; P = 0.029) and choledochal cyst (25% +/- 20%; P = 0.037). The 8-OHdG labeling index was significantly correlated with the grade of chronic hepatitis activity (Spearman r = 0.495; P = 0.037). The hepatocyte terminal deoxynucleotidyl transferase mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end-labeling index in KP (15% +/- 4%) was significantly higher than that in LT (5% +/- 2%; P = 0.018) and in choledochal cyst (3% +/- 2%; P = 0.010). Mitochondrial copy number was significantly less in KP than in LT (7.33 +/- 0.75 vs 8.91 +/- 1.32; P = 0.045) and in normal control (7.33 +/- 0.75 vs 9.20 +/- 1.20; P = 0.021). CONCLUSIONS: The early stage of BA is associated with stronger inflammatory reaction, augmented oxidative DNA, and mitochondrial DNA damage as manifested by higher immunoreactive 8-OHdG and apoptotic activities and by a decrease in mitochondrial copy number. PMID- 17873746 TI - A national sample of individuals who acquired hepatitis C virus infections in childhood or adolescence: risk factors for advanced disease. AB - OBJECTIVES: To describe hepatitis C virus (HCV)-related liver disease in a national cohort of patients who acquired their infections in childhood or adolescence and to assess risk factors for progressive disease and response to antiviral therapy. PATIENTS AND METHODS: Demographic, laboratory, and clinical outcome data on 246 individuals who acquired HCV infection before the age of 16 years were extracted from the UK HCV National Register database. Logistic regression analysis was used to investigate the independent effects of sex, age, duration and route of infection, and comorbidity on histological stage of liver disease. RESULTS: Median ages at enrollment and follow-up were 14.0 years (range, 2.2-29.6 years) and 19.2 years (range, 2.3-35.5 years), respectively. Mean duration of infection at enrollment was 8.5 years (standard deviation [SD], 3.3 years), and mean duration of follow-up was 4.5 years (SD, 4.5 years). Fifty-nine (24%) had persistently abnormal liver aminotransferase levels; 22% reported physical signs and symptoms of liver disease. Among 123 individuals with liver biopsies, 117 (95%) had abnormal histological findings. Ninety-eight individuals had biopsies referred for independent blind scoring; median Ishak grade and stage scores were 3 and 1, respectively. Presence of comorbidities (odds ratio [OR], 7.19; 95% CI, 2.00-26.17; P = 0.003) and female sex (OR, 0.31; 95% CI, 0.10-1.00; P = 0.05) were independently associated with histological stage scores greater than the median. A total of 110 individuals received antiviral therapy; 47% achieved a sustained response. CONCLUSIONS: HCV-related liver disease in those who acquired the infection in childhood or adolescence was mild for most, although comorbidity and female sex were associated with more advanced disease. Antiviral therapy in childhood or adolescence successfully eradicates the virus for many patients. PMID- 17873747 TI - Resting energy expenditure in children with inflammatory bowel disease. AB - OBJECTIVES: There is controversy in the literature regarding the effect of inflammatory bowel disease (IBD) on resting energy expenditure (REE). In many cases this may have resulted from inappropriate adjustment of REE measurements to account for differences in body composition. This article considers how to appropriately adjust measurements of REE for differences in body composition between individuals with IBD. PATIENTS AND METHODS: Body composition, assessed via total body potassium to yield a measure of body cell mass (BCM), and REE measurements were performed in 41 children with Crohn disease and ulcerative colitis in the Royal Children's Hospital, Brisbane, Australia. Log-log regression was used to determine the power function to which BCM should be raised to appropriately adjust REE to account for differences in body composition between children. RESULTS: The appropriate value to "adjust" BCM was found to be 0.49, with a standard error of 0.10. CONCLUSIONS: Clearly, there is a need to adjust for differences in body composition, or at the very least body weight, in metabolic studies in children with IBD. We suggest that raising BCM to the power of 0.5 is both a numerically convenient and a statistically valid way of achieving this aim. Under circumstances in which the measurement of BCM is not available, raising body weight to the power of 0.5 remains appropriate. The important issue of whether REE is changed in cases of IBD can then be appropriately addressed. PMID- 17873749 TI - Multiple exudative ulcers and pseudopolyps in allergic eosinophilic gastroenteritis that responded to dietary therapy. PMID- 17873748 TI - Vitamins A and E and pulmonary exacerbations in patients with cystic fibrosis. AB - BACKGROUND: Increased levels of oxidative stress result in pulmonary damage contributing to the development of chronic lung disease in cystic fibrosis (CF). The aim of this study was to investigate the longitudinal effect of serum vitamin A and E levels on the incidence of pulmonary exacerbations in pancreatic insufficient (PI) and pancreatic sufficient (PS) patients with CF. MATERIALS AND METHODS: Patient records were retrospectively examined over a 3-year period and serum vitamin A and E levels were retrieved. Subsequently, levels of vitamin A and E were prospectively measured over a 2-year period at the onset of intravenous antibiotic therapy for acute exacerbation and at the first recovery visit. RESULTS: Retrospectively, 597 pulmonary exacerbations were identified in 102 patients, 74 PI and 28 PS, with a mean age of 11.1 +/- 6.4 years (range, 1.5 27 y). An increased number of exacerbations was directly correlated with lower vitamin A and E levels, even within the normal range. Prospectively, 62 exacerbations were analyzed (43 PI patients and 19 PS patients). At onset of exacerbation, vitamin A and E levels were reduced in the PI patients (P < 0.001; P < 0.001) and the PS patients (P < 0.005; P < 0.07). CONCLUSIONS: Reduced serum levels of vitamin A and E even in the normal range are associated with an increased rate of pulmonary exacerbations in CF. Further studies are required to confirm the necessity of supplementation of vitamins A and E to PS patients. PMID- 17873750 TI - Pediatric jejunal gastrointestinal stromal tumor diagnosed by wireless capsule endoscopy. PMID- 17873751 TI - Frostbite of the esophagus. PMID- 17873752 TI - Percutaneous transesophageal gastrostomy (PTEG) placement in an infant. PMID- 17873753 TI - Subclinical neurological abnormalities in children with celiac disease receiving a gluten-free diet. AB - OBJECTIVES: Because clinically evident manifestations are frequent in adults with celiac disease (CD), we aimed to investigate whether early neurological abnormalities may be detected in children with CD. METHODS: Electroencephalography, electromyography, and somatosensory evoked potentials were performed in children with CD receiving a gluten-free diet. RESULTS: The neurophysiological tests revealed subclinical neurological abnormalities associated with CD in 3 (11%) of 27 children: 2 had peripheral polyneuropathy documented with electromyography, and 1 had prolonged latencies in somatosensory evoked potential. Magnetic resonance imaging showed abnormalities in 2 (7.4%) of children: pontine demyelinization in 1 and cortical atrophy in the other. CONCLUSIONS: Because the rate of neurological problems is increased in children with CD, neurological abnormalities should be carefully investigated early after the diagnosis of CD is made. PMID- 17873754 TI - Summary of the First International Gastrointestinal Eosinophil Research Symposium. PMID- 17873755 TI - Sarcoidosis: clinical, hormonal, and magnetic resonance imaging (MRI) manifestations of hypothalamic-pituitary disease in 9 patients and review of the literature. AB - Hypothalamic-pituitary (HP) sarcoidosis has 2 main endocrine manifestations: diabetes insipidus and hyperprolactinemia. We conducted the current study to investigate pituitary dysfunction and perform imaging of the HP area in patients both immediately following diagnosis and after treatment. The study included 6 men and 3 women, with a mean age of 30 years at the onset of sarcoidosis. All patients had both hormonal and magnetic resonance imaging (MRI) HP disorders. All patients had anterior pituitary dysfunction, 7 of them with associated diabetes insipidus. Nine patients had gonadotropin deficiency and 3 had hyperprolactinemia. MRI revealed infundibulum involvement in 5 patients, pituitary stalk thickness abnormality in 5, and involvement of the pituitary gland in 2, associated with other parenchymal brain or spinal cord lesions in 6 patients. All patients had multiple localizations of sarcoidosis, and 5 had histologically confirmed sinonasal localizations. Mean follow-up of the HP disorder was 7.5 years. All patients received prednisone. There was no correlation between the number of hormonal dysfunctions and the area of the HP axis involved as assessed by MRI. Although corticoid treatment was associated with a reduction of radiologic lesions, only 2 patients had partial recovery of hormonal deficiency. In conclusion, hormonal deficiencies associated with HP sarcoidosis frequently include hypogonadism (all patients) and to a lesser degree diabetes insipidus (7 of 9 patients). MRI abnormalities improved or disappeared in 7 cases under corticosteroid treatment, but most endocrine defects were irreversible despite regression of the granulomatous process. Most cases presented with multivisceral localizations and an abnormally high proportion of sinonasal localizations. PMID- 17873756 TI - Substitution of methotrexate for cyclophosphamide in Wegener granulomatosis: a 12 year single-practice experience. AB - We conducted a retrospective review to assess outcomes of therapy in patients with newly diagnosed Wegener granulomatosis (WG) using methotrexate (MTX) for mild to moderate disease and short-term treatment with cyclophosphamide (CYC) followed by MTX for severe disease. Patients with WG were included if their initial plan of therapy and subsequent care were directly supervised by the Cleveland Clinic Center for Vasculitis Care and Research. Severe disease (immediately life-threatening or involving critical organs) was initially treated with CYC and glucocorticoids. Mild to moderate disease was initially treated with MTX and glucocorticoids if serum creatinine was less than 2 mg/dL. Following initial improvement of severe disease, treatment was changed to MTX if serum creatinine was originally less than 2 mg/dL or had diminished to less than 2 mg/dL. Disease activity was determined at each visit and later converted to a Birmingham Vasculitis Activity Score, as modified for Wegener granulomatosis (BVAS/WG). Laboratory monitoring of disease and treatment toxicity was initially weekly and never less than monthly.Eighty-two (32%) of 253 patients with WG referred to the Center for Vasculitis Care and Research met eligibility criteria. Ineligible patients did not have new-onset disease or were not able to be followed principally in our center. Seventy percent of patients (57/82) initially had severe disease and received a short course of CYC for remission induction. In over half of these patients, illness was judged to be severe because of pulmonary hemorrhage; rapidly progressive glomerulonephritis, including need for dialysis; or neurologic abnormalities. All patients improved: remission was achieved in 50% (41/82) of patients within 6 months and in 72% (59/82) within 12 months. Sustained remission (BVAS/WG = 0 for at least 6 consecutive months) was ultimately achieved in 78% (64/82) of patients. Among the 75 (91%) patients who achieved remission of any duration, 45% relapsed within 1 year and 66% relapsed within 2 years following remission. Eighty-two percent of relapsed patients achieved subsequent remissions after additional treatment. About three-quarters of relapses were mild and promptly responded to treatment. Seventeen percent of patients developed serious infections. CYC-associated cystitis or bladder cancer did not occur in any patients. At least 1 form of permanent morbidity from WG alone was noted in 74.0% of patients. Three patients (3.7%) died over a median follow-up period of 4.5 years; no deaths were due to active disease. Although treatment was primarily directed toward achieving clinical improvement and not calculated to achieve marked lymphopenia, patients in whom treatment produced lymphocyte counts of 1000/mm was associated with a hazard ratio for relapse of 3.0, although the latter difference was not statistically significant. In patients with WG, a strategy that limits or avoids CYC therapy produced a frequency of remission comparable to that achieved with conventional CYC protocols, excellent survival, and avoidance of long-term CYC toxicity. However, relapses were common and incremental permanent morbidity occurred in most patients. While not a goal of therapy, when treatment produced marked lymphopenia, prolonged remissions were more likely. PMID- 17873757 TI - Cavernous sinus syndrome: a series of 126 patients. AB - The etiology of cavernous sinus syndrome (CSS) remains difficult to determine in spite of the development of neuroimaging techniques. We conducted the current study to identify clinical and imaging features that allow a reliable approach to the etiologic diagnosis of patients with CSS. We studied a consecutive series of 126 patients with CSS, defined as involvement of 2 or more of the third, fourth, fifth (V1, V2), or sixth cranial nerves, or involvement of only 1 of them in combination with a neuroimaging-confirmed lesion in the cavernous sinus. Tumors were the most common cause of CSS (80 patients). All patients with optic nerve involvement had a tumor. No patient with a normal MRI had a tumor. The lack of pain during the course of the disease (odds ratio [OR], 0.58; 95% confidence intervals [CI], 0.06-0.40), V2 involvement (OR, 12.17; 95% CI, 2.98-49.71), and male sex (OR, 3.2; 95% CI, 1.31-8.14) were independently associated with the presence of a tumor. Pain at the onset of disease (OR, 12.09; 95% CI, 3.14-46.50) and third cranial nerve involvement (OR, 4.9; 95% CI, 1.01-24.60) were independently associated with Tolosa-Hunt syndrome. PMID- 17873758 TI - Angioimmunoblastic T-cell lymphoma: clinical and laboratory features at diagnosis in 77 patients. AB - We retrospectively analyzed 77 patients with pathologically diagnosed angioimmunoblastic T-cell lymphoma from a single city. There were 43 men and 34 women; the median age was 64.5 years (range, 30-91 yr). Average time between first symptoms of the disease and diagnosis was 3.6 months. At diagnosis, peripheral nodes were present in all but 1 patient, and were generalized in 90% of cases. Constitutional symptoms were reported in 77% of cases and spleen enlargement in 51%. A cutaneous eruption--morbilliform, urticarial, or more polymorphic--was present in 45% of patients; in one-third of them, the eruption occurred after drug administration. Other clinical manifestations included pleuritis (22%); arthralgia or arthritis (17%); ear, nose, and throat involvement (14%); central or peripheral neurologic manifestations (10%); and ascites (5%). Most patients presented with advanced disease at diagnosis (bone marrow involvement in 60% of cases). The main laboratory abnormalities were elevated lactate dehydrogenase levels (71%), inflammatory syndrome (67%), hypergammaglobulinemia (50%), anemia (51%), and lymphopenia (52%). Auto- or disimmune manifestations were reported in one-third of patients: autoimmune hemolytic anemia was present at diagnosis in 19% of patients and thrombocytopenic purpura in 7%. Documented vasculitis was described in 12% of cases. Clonality was analyzed in lymph nodes in 47 patients: T-cell and B-cell clones were found in 45 (96%) and 20 (45%) patients, respectively. Chromosomal abnormalities were identified in 62% of cases: trisomies 3, 5, 18, 19, additional X chromosome, and deletion of chromosome 7 were the most common abnormalities. The current study underlines the diversity of presenting manifestations of angioimmunoblastic T cell lymphoma. PMID- 17873759 TI - Clinical significance of thyroid disease in patients with inflammatory myopathy. AB - We conducted the current study to determine the prevalence, incidence density, and clinical significance of thyroid disease in a series of 109 patients diagnosed with idiopathic inflammatory myopathy. We analyzed 109 patients diagnosed with idiopathic inflammatory myopathy during a 20-year period (1986 2006). Routine determination of thyroid profile, including hormone levels and antithyroid antibodies (antithyroid peroxidase and antithyroglobulin antibody systematically, and antithyroid-stimulating hormone receptor antibody when appropriate) was carried out at onset and at least once again during the follow up period. Human leukocyte antigen (HLA) study was performed by polymerase chain reaction sequence-specific oligonucleotide typing. Six patients (5.5%) developed thyroid disease (hypo- or hyperthyroidism), with an incidence density of 8.7 new cases per 1000 person-years; 4 of the 6 cases were of autoimmune origin (3.6%). Thyroid dysfunction, whether autoimmune or not, was clearly related with onset or relapse of disease activity. Neoplastic disease was detected in 3 of 4 (75%) patients with autoimmune thyroid disease, a significantly higher frequency than was observed in the remaining patients in the series (12 of 103, 11.7%; p < 0.05; RR: 22.8; 95% confidence interval, 2.2-236.6). HLA DRB1*04 was found in 4 of the 6 patients with thyroid disease and inflammatory myopathy. Thyroid disorders are clinically relevant in patients with inflammatory myopathies. An association was observed between autoimmune thyroid disease and cancer. Thyroid assessment is strongly recommended in patients with idiopathic inflammatory myopathy and clinical relapse. PMID- 17873760 TI - Pulmonary arterial hypertension: a rare complication of primary Sjogren syndrome: report of 9 new cases and review of the literature. AB - Primary Sjogren syndrome (pSS) is a fairly common autoimmune disease with glandular and extraglandular manifestations. Pulmonary involvement mainly corresponds to small airways and interstitial lung disease. Pulmonary arterial hypertension (PAH) is rare: to our knowledge, only 32 cases have been reported in pSS patients to date. PAH is a disease of the small pulmonary arteries characterized by vascular proliferation and remodeling, resulting in a progressive increase in pulmonary vascular resistance, and, ultimately, right ventricular failure and death. We report 9 new cases of pSS-associated PAH with a complete assessment including clinical characteristics (of both PAH and pSS), hemodynamic parameters, medical management, and outcome. We also review the 19 fully documented PAH patients with pSS reported in the English-language literature, therefore analyzing a total of 28 cases (27 women; mean age at PAH diagnosis, 50 +/- 11 yr; range, 23-68 yr). Functional impairment at diagnosis was severe, with a New York Heart Association (NYHA) functional class of III or IV in most cases. Seven of 15 (47%) patients for whom data were available had history or evidence of right heart failure at PAH diagnosis. Hemodynamic parameters were moderate to severe with a mean pulmonary artery pressure of 44 +/- 11 mm Hg (range, 24-60 mm Hg) and a cardiac index of 2.91 +/- 0.72 Lmin(-1)m(-2) (range, 1.36-3.88 Lmin(-1)m(-2)). Standard PAH therapy (endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, or prostanoids) was initially effective in some patients but had short-term and long-term failures. Some patients were treated with first-line immunosuppressants alone leading to improvement in some, but second-line standard PAH therapy was added in all cases thereafter. The best treatment strategy remains to be defined. Estimated survival rates were low (73% and 66% at 1 and 3 years, respectively). Compared with pSS patients without PAH, patients with pSS-associated PAH had Raynaud phenomenon, cutaneous vasculitis, and interstitial lung disease significantly more frequently. They also more frequently had antinuclear, anti-Ro/SSA, and anti-RNP autoantibodies, as well as positive rheumatoid factor and hypergammaglobulinemia. These data suggest that systemic vasculopathy, B-cell activation, and autoimmunity could play a role in the pathophysiology of pSS-associated PAH. In conclusion, this report underlines the rarity and severity of PAH in pSS patients. The best therapeutic regimen remains to be defined but should include standard PAH therapy and/or immunosuppressants. PMID- 17873762 TI - Gerald Westheimer: a paradigm for excellence in vision science research. Interview by Kenneth A. Polse. AB - Professor Gerald Westheimer has made enormous contributions to the field of vision science while introducing some of the most innovative and respected vision research of the twentieth century. Dr. Westheimer's achievements have been enhanced by an equally stellar reputation as a teacher and mentor. This biography and interview span 83 years of Dr. Westheimer's professional and personal life, from his childhood in Germany to his accomplishments at the University of California. PMID- 17873763 TI - Atypical fixation preference with anisometropia. AB - PURPOSE: To describe a child with hyperopia and anisometropia who manifests strabismus and amblyopia in the much less hyperopic eye. CASE REPORT: A 6-year old child presented with a history of strabismus and refractive error since infancy, which has been treated with glasses and patching. The present examination revealed 3 D of hyperopic anisometropia, intermittent exotropia, and amblyopia. The strabismus and amblyopia occur in the less hyperopic eye. Ocular health assessment including optical coherence tomography was normal. After patching therapy, the vision improved in the amblyopic eye. CONCLUSION: Amblyopia and strabismus need not always occur in the more ametropic eye when accompanied by anisometropia. PMID- 17873764 TI - Variability of the analysis of the tear meniscus height by optical coherence tomography. AB - PURPOSE: Tear meniscus height (TMH) is an established parameter indicative of tear film volume and has recently been determined using an optical coherence tomographer (OCT). The purpose of this study was to evaluate the inter and intra observer variability in TMH assessment using OCT. METHODS: Ten subjects (6 M, 4 F; aged 32.5 +/- 6.4 years) had 10 consecutive scans taken of their inferior central tear meniscus (5 scans originating at 90 degrees and 5 origination at 270 degrees) using the OCT2 (Humphrey-Zeiss). Images were analyzed by two observers using custom software on three separate occasions. Following a training session among observers, the images were reevaluated to assess differences in variability. Data were analyzed for differences within and across examiners, for the effect of examiner training and between scan directions. RESULTS: The mean TMH and tear volume collapsed across subjects were between 0.24 and 0.25 mm and 25 to 27 nL/mm, respectively. No difference was noted within observers. An interobserver mean volume difference (p = 0.044) was present but was eliminated post training (p = 0.167). Variability was less with scans originating at 90 degrees. CONCLUSIONS: The values of the TMH and tear volume are similar to those reported in the literature. Due to the interobserver differences observed, a training session between examiners may prove to be valuable, especially in a large or multicenter study. PMID- 17873765 TI - Pseudo forward ray-tracing: a new method for surface validation in cornea topography. AB - PURPOSE: A pseudo forward ray-tracing (PFRT) algorithm is developed to evaluate surface reconstruction in corneal topography. The method can be applied to topographers where one-to-one correspondence between mire and image points can be established. METHODS: The PFRT algorithm was applied on a corneal topographer designed and constructed at the VU University Medical Center, Amsterdam, The Netherlands. Performance of the algorithm was evaluated using artificial test surfaces and two sample eyes. The residual output of the PFRT algorithm is displayed as pixel displacements of actual feature points on the corneal image. Displacement of 1 pixel indicates submicrometer corneal height accuracy. RESULTS: PFRT residual increases with complexity of the measured surface. Using Zernike radial order 6, the mean residual for the artificial surfaces is subpixel. The mean residual for the regular cornea and the irregular cornea is 1.16 and 2.94 respectively. To some extent, increasing the Zernike radial order improves the accuracy. The improvement from order 6 to 20 is factor 2.3 for the irregular cornea. Using the residuals to further improve the accuracy brought local changes as high as 0.28 D in some areas of the reconstructed corneal power map. CONCLUSION: PFRT can be used to evaluate how close a reconstructed corneal surface is to the actual one. The residue information obtained from this algorithm can be displayed simultaneously with the corneal image. This provides accurate information about the corneal shape that is useful for application in laser refractive surgery. PMID- 17873766 TI - What does Optometry and Vision Science present? PMID- 17873770 TI - Fixation in patients with juvenile macular disease. AB - PURPOSE: The instability of fixation with central scotoma has been mainly studied in patients with age-related macular diseases (MDs). However, early macular lesions can lead to different characteristics of fixation. The aim of this work was to study fixation in patients with juvenile MD. METHODS: Eye movements of 10 patients and 10 controls were monitored during fixation. Visual fields were assessed by static perimetry to determine the extent of the field defects. Eye movements were separated into saccades and drifts, with fixation stability assessed by bivariate contour ellipse area (BCEA). To quantify the number and location of preferred retinal loci (PRL), the kernel density estimator and expectation maximization for mixtures of gaussians were used. RESULTS: Patients have worse fixation stability than controls and large BCEAs resulted in more than one PRL. It was found that central field defects (10 degrees) have negative correlation with the size of BCEA. In addition, the meridian of saccades during fixation was correlated with the meridian inter-PRL. CONCLUSIONS: Patients with juvenile MDs have large BCEAs, frequently associated with two PRL. Similar results had been found for patients with age-related MDs. Also, the meridian of involuntary saccades during fixation was found to be correlated with the location of PRLs, suggesting a useful role of these movements in alternating between them. PMID- 17873769 TI - Confocal microscopy and albumin penetration into contact lenses. AB - PURPOSE: To develop a novel in vitro method to detect the depth of penetration of the tear film protein albumin into contact lens materials using confocal laser scanning microscopy (CLSM). METHODS: A poly-HEMA-based hydrogel (etafilcon A) and a silicone hydrogel material (lotrafilcon B) were examined. In vitro, bovine serum albumin (BSA) was labeled with 5-(4,6-dichloro-s-triazin-2-ylamino) fluorescein hydrochloride (DTAF). The lenses were incubated in this protein solution (0.5 mg/ml) at 37 degrees C. After 1 and 7 days incubation, the lenses were examined using CLSM (Zeiss 510, config. META 18) and the location of the fluorescently labeled BSA was identified. RESULTS: BSA adsorption on the surface and penetration into the lens matrix occurred at a higher concentration for etafilcon compared to lotrafilcon (p < 0.001). For both materials, BSA was detected on the surface after 1 day of incubation. Significant levels of BSA were detected within the matrix of etafilcon after as little as 1 day (p < 0.001), but no BSA was detected in the matrix of lotrafilcon at any time (p > 0.05). CONCLUSION: CLSM can be successfully used to examine the depth of penetration of fluorescently labeled proteins into various hydrogel polymers. Our results show that etafilcon lenses both adsorb BSA on the surface and absorb BSA within the matrix, whereas lotrafilcon B adsorbs small amounts of BSA on the surface only. PMID- 17873771 TI - The glare hypothesis of macular pigment function. AB - PURPOSE: Discomfort and reduced visual performance due to glaring light conditions are common complaints for most individuals. Past studies have shown that macular pigment (MP) reduces discomfort due to glare. In this study, we evaluated whether MP was related to visual performance under glare conditions. METHODS: Thirty-six healthy subjects participated (age range, 18 to 41). Spatial profiles of MP optical density were measured using heterochromatic flicker photometry with a Newtonian-view macular densitometer. Photostress recovery and grating visibility under veiling conditions were assessed in a Maxwellian-view optical system. Both experiments used six monochromatic lights (from 440 to 620 nm) and a broadband xenon white. For the veiling glare experiment, subjects fixated a 1 degrees diameter disk containing a black and white 100% contrast grating stimulus. The intensity of an annulus (the glare source) with an 11 degrees inner and 12 degrees outer diameter was adjusted by the subject until the grating stimulus was no longer seen. For the photostress recovery experiment, the time required to detect a 1 degrees -diameter grating stimulus (detailed above) after a 5-s exposure to a 2.5 microW/cm2, 5 degrees -diameter disk was recorded. Both central and eccentric (10 degrees temporal retina) viewing conditions were assessed. RESULTS: MP at 30' eccentricity ranged from 0.08 to 1.04 OD, and was found to dramatically reduce the deleterious effects of glare. Visual thresholds under glare conditions were strongly related to MP density (e.g., r = 0.76, p = 0.0001 when using white light). Photostress recovery time, after exposure to xenon-white light, was significantly shorter for subjects with higher MP levels (r = -0.79, p = 0.0001). Both photostress recovery and veiling glare functions were well-described by the photopic spectral sensitivity function (Vlambda). CONCLUSIONS: MP is strongly related to improvements in glare disability and photostress recovery in a manner consistent with its spectral absorption and spatial profile. PMID- 17873772 TI - Redirecting gaze to improve the cosmetic appearance of strabismus. AB - PURPOSE: We studied a behavioral technique in which strabismics can reduce the detectability of their eye turn by appropriately redirecting their gaze. We tested the efficacy of this technique for various amounts of strabismus and different positions of gaze. METHODS: We took digital images of a model gazing in different lateral directions and digitally edited them to simulate fixation with one eye on different lateral locations whereas the other eye was misaligned from the first by +/-0, 6, 12, 18, 24, and 30 Delta. Then we asked 22 lay observers to examine each of the images and to report whether or not they perceived eye contact and normal gaze. RESULTS: The observers reported that our model appeared to look normal and gave them eye contact two-thirds of the time for up to 18 Delta of exotropia and 12 of esotropia when she looked half her prismatic deviation to the side opposite her eye turn. CONCLUSION: By appropriately directing their gaze, both exotropes and esotropes can improve the cosmetic appearance of their strabismus and increase the perception that they are looking at the observer. This may be useful during job interviews and other social encounters where eye contact and a good impression are critical. A drawback is that large amounts of strabismus may require the gazer to look far to the side of the observer's head where it may be difficult to maintain gaze and the observer's facial expression may be hard to read. However, all patients may be counseled on which eye to look at when engaging in conversation, as looking at the appropriate rather than the inappropriate eye can reduce the perceived amount of their strabismus. Also, when their portrait is being taken, the full amount of eccentric gaze could easily be used. PMID- 17873773 TI - Hierarchical linear modeling of visual acuity change over time: rate of functional recovery after macular hole surgery. AB - PURPOSE: To examine acuity recovery rate after Macular Hole (MH) surgery, using Hierarchical Linear Modeling (HLM) with linear and curvilinear regression analysis. METHODS: Preoperative MH diameter (OCT) and acuity (ETDRS) were recorded in 20 eyes. Acuities were tested during follow-up (6 to 23 months), with three to eight measurements per eye. The resulting 95 acuities were analyzed using HLM. Variability at the level of the person was explained by change over time, using a natural logarithm conversion. Across patients, MH diameter was used to predict slopes and intercepts at the level of the individual. RESULTS: MH diameter was able to account for significant amounts of variability in preoperative acuity (intercept) and significantly influenced rate of functional recovery (slope). A nonlinear approach to the data accounted for the largest amount of variance. CONCLUSIONS: Participants with larger MHs recovered relatively more acuity sooner while eyes with smaller MHs had better absolute acuity outcome. HLM provides important insight into the recovery process after MH surgery and is more flexible with follow-up data. In the context of MH treatment, most recuperation occurred during the initial 6 months. PMID- 17873774 TI - Objective accommodation measurement with the Grand Seiko and Hartinger coincidence refractometer. AB - PURPOSE: Subjective push-up tests and dynamic retinoscopy are standard clinical accommodation tests. These are inadequate for assessing if accommodation can be restored in presbyopes. Commercially available clinical autorefractors offer potentially reliable methods for objective accommodation measurement. This study evaluated accuracy and reliability of the Grand Seiko WR-5100K autorefractor for objective accommodation measurement in young adults. METHODS: Twenty-two subjects, aged 21 to 30 years (mean 25.6 +/- 2.26) participated. Three methods were used to stimulate and measure accommodation: (1) subjective push-up test in free space, (2) a near target pushed-up on a near-point rod and the response measured with the WR-5100K and a Hartinger coincidence refractometer (HCR), and (3) a distant target viewed through increasing powered negative trial lenses and the response measured with the WR-5100K and the HCR. Trial lens calibration procedures were also used to test the accuracy of the instruments. RESULTS: Average maximum accommodative amplitude with the subjective push-up test was 7.74 D +/- 0.36 D (mean +/- SE). For a 5 D stimulus, accommodation of 4.68 D +/- 0.10 D (mean +/- SE) and 4.13 D +/- 0.09 D was measured with the WR-5100K and the HCR, respectively. With a distant target viewed through a -5.00 D trial lens, the WR 5100K measured 4.07 D +/- 0.09 D and the HCR measured 4.05 D +/- 0.09 D of accommodation. Maximum mean response measured with trial lens-induced accommodation was 5.67 D +/- 0.15 D with the WR-5100K and 5.77 D +/- 0.18 D with the HCR. CONCLUSIONS: The subjective push-up test overestimated accommodative amplitude relative to the objective measures. The WR-5100K showed good agreement in the responses measured for both pushed-up near targets and a distant target viewed through trial lenses with the HCR, a widely used laboratory instrument. The Grand Seiko WR-5100K, a commercially available instrument, has been demonstrated to be well suited for clinical, objective accommodation measurement using a population of normal young adults. PMID- 17873775 TI - An evaluation of the ConfoScan3 for corneal endothelial morphology analysis. AB - PURPOSE: We evaluated the ConfoScan3 confocal microscope and its associated software that allows automated analysis of the corneal endothelial morphology. METHODS: Images were taken on 30 normal subjects and 29 contact lens wearers with the Konan SP-9000 specular microscope and the ConfoScan3. The Konan images were analyzed with the KSS-300 software (center method). The Confoscan3 images were first analyzed with the automated method and then edited manually (semiautomated method). The agreement between methods was evaluated by calculating the difference between pairs of measurements, determining the mean and standard deviation of these differences, and the 95% limits of agreement. RESULTS: For normal subjects, all methods gave similar density values. The agreement with the Konan system was slightly better for the semiautomated method than the automated method. The automated method overestimated the degree of polymegethism (p < 0.001) and pleomorphism (p < 0.001). The semiautomated method showed substantial improvement. For contact lens wearers, agreement with the Konan system was poor for both automated and semiautomated methods. The automated method overestimated the degree of pleomorphism (p < 0.001) and the semiautomated method showed only modest improvement (p < 0.1). Both methods overestimated pleomorphism (automated p < 0.001; semiautomated p < 0.025). CONCLUSIONS: When using ConfoScan3 to evaluate the corneal endothelium of normal subjects, investigators should manually edit the processed images to achieve results comparable with the Konan system. When evaluating contact lens wearers, values from the ConfoScan3 are not interchangeable with those from the Konan system. PMID- 17873776 TI - Contact Lenses in Pediatrics (CLIP) Study: chair time and ocular health. AB - PURPOSE: Despite several studies that show 8- to 11-year-old children are capable of wearing a various contact lens modalities, parents often report that their eye care practitioner would not fit their child with contact lenses until the child was about 13 years old. We conducted the Contact Lenses in Pediatrics (CLIP) Study to compare contact lens fitting and follow-up between 8- to 12-year-old children and 13- to 17-year-old teenagers. METHODS: At the baseline visit, all subjects underwent a contact lens fitting, including visual acuity, a manifest refraction, autorefraction, and biomicroscopy. Subjects then underwent contact lens insertion and removal training, which consisted of talking about contact lens care as well as inserting and removing a contact lens three times. Subjects returned for follow-up visits at 1 week, 1 month, and 3 months, and visual acuity, contact lens fit assessment, and biomicroscopy were performed. The time of the fitting, the insertion and removal training, and each follow-up visit were measured individually and added for a total chair time. Biomicroscopy examinations were conducted according to a standardized protocol. RESULTS: We enrolled 84 children and 85 teens in the study. Of the 169 subjects, 93 (55.0%) were female, 78 (46.2%) were white, 44 (23.3%) were Hispanic, and 28 (17.6%) were black. The mean (+/- SD) total chair time for children was 110.6 +/- 39.2 min, significantly more than 95.3 +/- 25.2 min for teens (Student's t-test, p = 0.003). Most of the difference was caused by insertion and removal training, which lasted 41.9 +/- 32.0 min for children and 30.3 +/- 20.2 min for teens (Student's t-test, p = 0.01). The presence of conjunctival staining increased from 7.1% of the subjects at baseline to 19.9% of the subjects at 3 months (chi2, p = 0.0006), but the changes were similar between children and teens. No other biomicroscopy signs increased significantly over the 3-month period. CONCLUSIONS: The total chair time for children is approximately 15 min longer than teens, but most of that difference is explained by longer time spent teaching children insertion and removal. Because insertion and removal is generally taught by staff members, the eye care practitioner's time with the patient is similar between children and teens. Furthermore, neither children nor teens experienced problems related to contact lens wear during the study. Eye care practitioners should consider routinely offering contact lenses as a treatment option, even for children 8 years old. PMID- 17873777 TI - Comparison of IOP measurements between ORA and GAT in normal Chinese. AB - PURPOSE: To compare intraocular pressure (IOP) obtained from the ocular response analyzer (ORA) and Goldmann applanation tonometer (GAT) on a group of normal Chinese. METHODS: One hundred twenty-five normal subjects were recruited, with one eye randomly selected for this study. Each eye was measured first with the noncontact tonometer ORA, followed by the GAT and ultrasound pachometry, in a randomized order. Four readings were obtained from the ORA, and three measurements were taken with the GAT. The mean was used for analysis. The ORA provided a Goldmann-correlated IOP (IOPg) and a corneal-compensated IOP (IOPcc). Three central corneal thickness (CCT) values were measured using an ultrasound pachometer, and the mean was used for analysis. RESULTS: IOP obtained from the ORA was similar to that from the GAT (IOPg minus GAT: mean difference = 0.33 mm Hg, 95% limits of agreement = 4.55 to -4.44 mm Hg; IOPcc minus GAT: mean difference = 0.24 mm Hg, 95% limits of agreement = 4.83 to -5.07 mm Hg). CCT was positively associated with corneal hysteresis (CH) (r2 = 0.30, p < 0.01), corneal resistance factor (r2 = 0.38, p < 0.01), GAT (r2 = 0.09, p < 0.01) and IOPg (r2 = 0.16, p < 0.01). IOPcc was not associated with CCT (r2 = 0.01, p = 0.33). CONCLUSIONS: Both IOPg and IOPcc have good agreement with GAT on normal subjects. The influence of CCT on IOPcc was insignificant. PMID- 17873778 TI - To the editor: risk of corneal inflammatory events with silicone hydrogel and low Dk hydrogel extended contact lens wear: a meta-analysis. PMID- 17873780 TI - Deletion 22q11.2 syndrome--implications for the intensive care physician. AB - OBJECTIVE: To report on the experience of a pediatric intensive care unit (PICU) with patients with deletion 22q11.2 syndrome: 1) to delineate the clinical characteristics and management of these patients; 2) to assess whether these patients were managed appropriately, especially in terms of blood transfusion; and 3) to make recommendations for PICU management. DESIGN: Retrospective assessment of medical records of patients with fluorescent in situ hybridization proven 22q11 deletion admitted to the PICU at the Children's Hospital at Westmead, Sydney. SETTING: PICU in a tertiary university-affiliated children's hospital. PATIENTS: Sixty-five consecutive admissions in 40 patients with diagnosis of 22q11 deletion over a 4-yr period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-seven (57%) of 65 admissions were postoperative cardiac surgical and accounted for the most common reason for admission to the PICU. Thirteen (20%) admissions were for velopharyngeal/laryngeal problems. Four (6%) admissions were associated with hypocalcemia, with two being first presentations. Five (12.5%) of 40 patients had immune dysfunction, one of whom developed cytomegalovirus pneumonitis. Twenty-nine (72.5%) patients received blood products either immediately before PICU admission or in the PICU. Of these, 16 received nonirradiated cellular blood products. There were two deaths from complications of congenital heart disease. CONCLUSIONS: PICUs need to be familiar with deletion 22q11.2 syndrome, especially the recommended use of irradiated and cytomegalovirus-seronegative blood components in these immunocompromised patients. The guidelines were inconsistently followed in the cohort of patients reported here. The extent of this problem may be more widespread in PICUs, and we recommend that individual units review their practice in this regard. Hypocalcemia may manifest at any time, and a regular survey of the calcium status is required in the intensive care setting. Admission to PICU should afford the opportunity to invite subspecialty referral and optimize extended care. PMID- 17873782 TI - Dexmedetomidine: do we know enough? PMID- 17873783 TI - Using a computer-driven system to wean children from mechanical ventilation. PMID- 17873784 TI - It's not easy to save a life. PMID- 17873785 TI - Caring for children in a persistent vegetative state: complex but manageable. PMID- 17873786 TI - Extracorporeal support for septic shock. PMID- 17873787 TI - Probiotics in the critically ill: handle with care! PMID- 17873788 TI - Blood transfusions in patients with 22q11.2 deletion syndrome: assessment of risk requires identification of the at-risk patient. PMID- 17873789 TI - Steroids use in pediatric cardiac surgery: more questions. PMID- 17873790 TI - Surfactant treatment of aspiration-induced lung injury in children. PMID- 17873792 TI - Organ donation after cardiac death: are we willing to abandon the dead-donor rule? PMID- 17873794 TI - Site of intubation and duration of mechanical ventilation in pediatric status asthmaticus. PMID- 17873797 TI - The safety zone of percutaneous cervical approach: a dynamic computed tomographic study. AB - STUDY DESIGN: A prospective study using computed tomography (CT) scans. OBJECTIVE: To identify the structures at risk and the safety zone of a percutaneous cervical approach. SUMMARY OF BACKGROUND DATA: A percutaneous cervical approach may injure the important structures of the anterior neck. However, the dynamic locations of vital structures and the structures at risk by routine trajectory have not been analyzed. METHODS: Thirty patients were enrolled for this study. We obtained the CT scans of the cervical spine at each level of the intervertebral disc from C3-C4 to C6-C7, after manually pushing the airway in the same position and manner of discography. The patients ingested contrast materials for imaging of their digestive tracts and were injected intravenous contrast materials for imaging of vascular structures, just before obtaining images. We estimated the distances from the operator's fingertip to the digestive tract on the left side and to the carotid artery on the right side, at each level. The safety zone was determined by the sum of 2 distance calculations. We identified the anatomic structure at risk by simulated needle insertion toward the center of the disc through the safety zone. RESULTS: At C3-C4, the safety zone was measured 18.9 +/- 6.6 mm. The superior thyroidal artery (STA) was located in the safety zone of C3-C4 in 86.7%. At C4-C5, the safety zone was measured 23.5 +/- 6.5 mm. The STA and the right lobe of the thyroid gland (TG) were located in the safety zone in 26.7% and 30%, respectively. At C5-C6, the safety zone was measured 33.7 +/- 6 mm. The TG was located in the safety zone of C5-C6 in 76.7%. At C6-C7, the safety zone was 29.2 +/- 4.5 mm. The TG was located on the approach plane in 90%. CONCLUSION: The safety zone was wider at the distal level (C5-C6, C6-C7) than at the proximal level (C3-C4, C4-C5). The safest needle entry point should be between the pushing point of the airway and the pulsating point of the carotid artery. In addition, the needle should be approached toward the center of the disc. A percutaneous cervical approach allows a low risk of pharyngoesophageal structure injury and is considered a safe diagnostic technique in dynamic imaging studies. PMID- 17873798 TI - Multilevel cervical oblique corpectomy in the treatment of ossified posterior longitudinal ligament in the presence of ossified anterior longitudinal ligament. AB - STUDY DESIGN: Clinical study. OBJECTIVE: To highlight the value of the oblique corpectomy in managing patients with cervical myelopathy caused by extensive ossified posterior longitudinal ligament (OPLL) who also have a coexisting ossified anterior longitudinal ligament (OALL). SUMMARY OF BACKGROUND DATA: OPLL, OALL, and diffuse idiopathic skeletal hyperostosis (DISH) may coexist, and the surgical treatment is varied. Patients with cervical myelopathy who are asymptomatic for the OALL may be managed by either anterior or posterior approaches, while those with dysphagia are best managed by an anterior approach that can deal with both pathologies simultaneously. The OALL resection is indicated only if symptomatic. The central corpectomy, while a good option for anterior decompression, requires complex reconstruction procedures. The oblique corpectomy preserves the ventral half of the vertebral body and does not require stabilization. METHODS: In a series of 135 patients undergoing multilevel oblique corpectomy for cervical myelopathy, 3 had OPLL with massive OALL that was asymptomatic. The OPLL was removed using microdrills while preserving the OALL. Preoperative and postoperative MR imaging assessed cord compression and spinal alignment, whereas dynamic plain roentgenography assessed stability. Patients were assessed clinically for signs of dysphagia and dysphonia. RESULTS: The cervical myelopathy improved in all 3 patients at a follow-up of 3 years, 1 year, and 6 months, respectively, with no development of dysphagia. One patient had a Horner's syndrome that improved by 6 months and another had a C5 radiculopathy that was improving by 6 months. Imaging showed good decompression of the spinal cord, with no kyphosis or instability. CONCLUSION: The oblique corpectomy is a surgical option in patients with asymptomatic OALL in the setting of progressive myelopathy due to OPLL with intrinsic stability as a result of their OALL. This technique avoids a multilevel central corpectomy that is associated with significant instability often requiring reconstructive procedures. PMID- 17873799 TI - Mini-thoracotomy or thoracoscopic treatment for medially located thoracic herniated disc? AB - STUDY DESIGN: A retrospective cohort study. OBJECTIVE: Comparison of the mini thoracotomy (mini-TTA) and thoracoscopy for the treatment of calcified thoracic herniated disc. SUMMARY OF BACKGROUND DATA: Thoracoscopy has been popularized at the cost of the traditional thoracotomy for the treatment of calcified herniated discs. However, the learning curve is steep. Given the low incidence of herniated thoracic discs, it will be difficult for a group of spinal surgeons to gain experience. Newer, minimally invasive techniques with a nearly absent learning curve are evolving. One of these techniques is the mini-TTA. METHODS: Retrospectively, the charts of patients that underwent a mini-TTA or thoracoscopy were retrieved. RESULTS: Seven patients underwent a thoracoscopy, and 21 a mini TTA. Although the groups are limited, a statistical significant difference in gender, age, duration of surgery, duration of the necessity of a chest drain, intraoperative blood loss, or duration of the postoperative stay on the intensive care unit was not reached. At the last follow-up in the thoracoscopic group, 2 patients had some neuropathic thoracic incisional pain. In all patients, a complete removal of the calcified disc was ascertained with a postoperative computed tomography scan. CONCLUSION: The mini-TTA has some theoretical advantages over a thoracoscopy. It is also a minimally invasive approach. The thoracoscopy has a steep learning curve, whereas the mini-TTA is simple to apply. Classic microsurgical bimanual techniques can be used. PMID- 17873800 TI - Multiple extradural arachnoid cysts: report of two operated cousin cases. AB - STUDY DESIGN: Report of 2 operated cousin cases of the multiple spinal extradural arachnoid cysts. OBJECTIVE: To report the operative findings of cousin cases of the multiple spinal extradural arachnoid cysts and analyze a genetic etiology with the pedigree of all family members. SUMMARY OF BACKGROUND DATA: Spinal extradural arachnoid cyst is a relatively rare condition that occupies the intraspinal space and sometimes causes neurologic disturbances. The exact etiology is unknown since most reported cases are sporadic. Minimally invasive treatments have been recently applied to a single extradural arachnoid cyst. However, it is still unknown which minimally invasive treatments can be applied to the multiple extradural arachnoid cysts. METHODS: We experienced 2 cousin cases of multiple spinal extradural arachnoid cysts. Operative findings were described. The pedigree of all family members was made, and a genetic etiology was discussed. RESULTS: Minimally invasive treatment was tried in Case 1. However, it failed to remove all cysts completely. Each cyst had each stalk communicating with subarachnoid space in both cases. Pedigree showed that the mode of inheritance was likely autosomal dominant. CONCLUSION: When the cysts are multiple, it is necessary to identify a dural defect in each cyst. The etiology of the multiple extradural arachnoid cysts may be hereditary. PMID- 17873801 TI - Delayed presentation of pulmonary polymethylmethacrylate emboli after percutaneous vertebroplasty. AB - STUDY DESIGN: Literature review concerning pulmonary embolism of polymethylmethacrylate (PMMA) material following percutaneous vertebroplasty and a report on 2 new cases. OBJECTIVE: To inform clinicians about delayed clinical manifestation of pulmonary embolism of polymethylmethacrylate material after percutaneous vertebroplasty, pathophysiology, precautions, and therapeutic management of this complication. SUMMARY OF BACKGROUND DATA: Percutaneous vertebroplasty is a minimal invasive intervention used to treat vertebral fractures, which yields good therapeutic results and rarely produces complications. Nevertheless, serious complications may occur. Pulmonary PMMA embolism, which has been recently reported in some cases, is one of these. METHODS AND RESULTS: We report on 2 cases of pulmonary embolism of PMMA material after percutaneous vertebroplasty. In the case of a 45-year-old female patient, symptoms of pulmonary embolism arose with a delay of 3 days following percutaneous vertebroplasty. A therapy with low-molecular-weight heparin, Enoxaparin, enabled recovery from pulmonary failure. The second case occurred without detection of any cement leakage into the paravertebral venous system, neither intraoperatively nor perioperatively. The existence of PMMA in pulmonary vessels was detected 1 year later and remained asymptomatic. CONCLUSION: These 2 cases allow us to conclude that the risk of pulmonary embolism of PMMA might be underestimated. We propose routine chest radiograph following every vertebroplasty, in order to detect pulmonary PMMA embolism and thereby prevent serious delayed cardiopulmonary failures. PMID- 17873802 TI - Diffuse spine involvement in sarcoidosis with sternal lytic lesions: two case reports. AB - STUDY DESIGN: Case report. OBJECTIVE: To report 2 cases of sarcoidosis with a diffuse vertebral involvement, associated with a rare location in the sternum. SUMMARY OF BACKGROUND DATA: Sarcoidosis is a systemic disease of unknown cause with various clinical and radiologic manifestations. Bone involvement is rare (1% 13% of cases). Vertebral involvement is very uncommon. Lytic lesions, sclerotic lesions, or both of these patterns may be observed. METHODS: One patient complained of diffuse bone pain; the second patient was asymptomatic. Each patient had radiograph, CT, and MRI of the spine. The second patient also underwent a PET/CT FDG-(18F). Sternal bone biopsy was performed in both patients. Pathologic findings indicated typical pattern of bone sarcoidosis. Clinical and biologic improvement was noticed after treatment with corticosteroids. RESULTS: In our 2 cases, radiograph, CT, MRI, and PET/CT findings were evocative of diffuse spine involvement in sarcoidosis associated with sternal lytic lesions. This suspicion was confirmed by histopathologic findings, which found a typical pattern of sarcoidosis. CONCLUSION: These 2 cases emphasize the value of CT, MRI, and FDG-(18F) PET/CT for the diagnosis of diffuse spinal involvement in sarcoidosis and describe an exceptional association with sternal lytic lesions. PMID- 17873804 TI - 2006 SRS presidential address: embracing opportunities in exciting times. PMID- 17873805 TI - Spine surgery at a crossroads: does economic growth threaten our professionalism? PMID- 17873807 TI - The effect of mid-thoracic VEPTR opening wedge thoracostomy on cervical tilt associated with congenital thoracic scoliosis in patients with thoracic insufficiency syndrome. AB - STUDY DESIGN: Prospective clinical trial of vertical expandable prosthetic titanium rib (VEPTR) surgery in patients with congenital thoracic scoliosis with thoracic insufficiency syndrome and cervical tilt. OBJECTIVE: Report efficacy and safety of VEPTR mid-thoracic opening wedge thoracostomy in treatment of cervical tilt and head/truncal decompensation in children with thoracic insufficiency syndrome associated with thoracic congenital scoliosis. SUMMARY OF BACKGROUND DATA: Cervical tilt in children is a rare problem, usually associated with congenital cervical or cervical-thoracic scoliosis, and in progressive deformity, surgical fusion or hemi-vertebrectomy risks neurologic injury, loss of motion of the cervical spine, and unknown effect on pulmonary function. VEPTR patients with congenital scoliosis can have severe neck tilt with poor cosmesis, with the risk of neck pain in adulthood. VEPTR mid-thoracic opening wedge thoracostomy treats thoracic insufficiency syndrome, and paradoxically also appears to improve the neck alignment cosmesis. MATERIALS METHODS: Patients with fused ribs and congenital scoliosis, thoracic insufficiency syndrome, and cervical tilt were treated with VEPTR mid-thoracic thoracostomy. Complication rates, respiratory outcome, pulmonary function tests in older children, Cobb angles, head/truncal decompensation, T1 oblique take-off, space available for lung, height of the thoracic spine, and cervical tilt angle were measured. RESULTS: Fourteen patients with cervical tilt, fused ribs, progressive congenital scoliosis, and TIS were treated. The primary thoracic scoliosis and space available for lung improved, cervical tilt stabilized, and head and truncal decompensation improved. One child was weaned off a ventilator. Complications included device migration, infection, and transient brachial palsy. CONCLUSION: Mid-thoracic VEPTR opening wedge thoracostomy can stabilize cervical tilt associated with thoracic congenital scoliosis and fused ribs and may be an alternative to cervicothoracic spine fusion or hemi-vertebrectomy in some young children. PMID- 17873808 TI - Posterior lumbar interbody fusion versus posterolateral fusion in adult isthmic spondylolisthesis. AB - STUDY DESIGN: A prospective study with historical controls. OBJECTIVE: To compare the outcome of posterior lumbar interbody fusion (PLIF) and posterolateral fusion (PLF) in adult isthmic spondylolisthesis. SUMMARY OF BACKGROUND DATA: On theoretical grounds, PLIF has been suggested to result in an improved outcome compared with PLF. Data to support this view, however, are lacking. METHODS: A total of 86 patients (age range, 18-55 years) with adult isthmic spondylolisthesis were operated on with PLIF. The comparison group consisted of 77 patients operated on with PLF with iliac bone autograft, 40 with and 37 without pedicle fixation. The 2 groups had similar socioeconomic, age and sex distribution, level of pain, and disability. Inclusion criteria and outcome measurements were identical in both groups. The PLIF group was operated on with autograft and carbon fiber ramps with pedicle fixation. Before surgery and at the 2-year follow-up, pain (VAS) and functional disability were quantified by the Disability Rating Index (DRI, 0-100) and the Oswestry Disability Index (ODI). The global outcome was assessed by the patient as much better, better, unchanged, or worse. RESULTS: The follow-up rate was 98% in the PLIF group and 97% in the PLF group. In PLIF patients, pain index improved from 66 to 35 (P < 0.0001) and the DRI from 47 to 30 (P < 0.01). The levels of pain and DRI were similar to that of the PLF group (pain 37, DRI 29, not significant), and the ODI was identical in both groups (25); 74% of the patients in both groups classified the results as much better or better. CONCLUSION: Type of fusion, PLIF or PLF, does not affect the 2-year outcome of surgical treatment of adult isthmic spondylolisthesis. Despite the theoretical advantages of PLIF, no improvement on patient outcome compared with posterolateral fusion could be demonstrated, questioning the need of anterior support in short lumbar fusions. PMID- 17873809 TI - Clinical and radiographic results after implant removal in idiopathic scoliosis. AB - STUDY DESIGN: Prospective radiographic and clinical analysis of patients with idiopathic scoliosis who had complete implant removal following posterior spinal fusion (PSF) at least 2 years previously. OBJECTIVE: To evaluate the clinical and radiographic effect of implant removal after PSF for idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Occasionally, implants must be removed following instrumented PSF. Indications for removal include infection and late operative site pain. Previously, it has been thought that there was little morbidity associated with implant removal in the presence of a solid fusion. However, recent studies have reported loss of coronal correction after implant removal in patients who had a PSF for adolescent idiopathic scoliosis. Few long-term studies have assessed the clinical or radiographic results of complete implant removal after PSF. METHODS: We identified 56 patients who had undergone PSF for idiopathic scoliosis and subsequently had complete removal of all instrumentation. None of these patients had a pseudarthrosis at the time of implant removal. After IRB approval, 43 of 56 (77%) patients returned for new standing posteroanterior and lateral spine radiographs and completion of an SRS 22 questionnaire. RESULTS: For the 43 patients who had new radiographs and completed an SRS-22, the time from the original PSF to complete implant removal averaged 2.9 years (range, 7 months to 7.25 years). Twenty-two patients had implants removed because of infection, and 21 patients had implants removed secondary to pain. The average time from implant removal to completion of the most recent radiographs and SRS-22 questionnaire was 9.5 years (range, 3.2-17.9 years). Patients were considered to have had progression of deformity after implant removal if their Cobb angle measurements increased by more than 10 degrees . Two patients had 11 degrees to 20 degrees of coronal plane progression of their main thoracic curve. No patient had more than 10 degrees of coronal plane progression of a lumbar curve. Sagittal curve progression was identified more frequently. Nineteen patients had between an 11 degrees and 20 degrees increase in thoracic kyphosis, and 5 patients had >20 degrees of thoracic kyphosis progression. Patients with >20 degrees of thoracic kyphosis progression after implant removal had greater thoracic kyphosis before surgery and larger main thoracic and lumbar coronal curves at the time of implant removal. Progressive kyphosis did not correlate with: reason for implant removal, length of follow-up, or time from fusion to implant removal. Although total SRS-22 scores correlated inversely with increased thoracic kyphosis, this trend did not reach statistical significance. CONCLUSION: Implant removal after PSF for idiopathic scoliosis may be complicated by progression of deformity. Patients requiring implant removal should be appropriately counseled and monitored. PMID- 17873810 TI - Results of lumbar pedicle subtraction osteotomies for fixed sagittal imbalance: a minimum 5-year follow-up study. AB - STUDY DESIGN: Retrospective study. OBJECTIVE: To report results at a minimum 5 years after pedicle subtraction osteotomy for fixed sagittal imbalance. SUMMARY OF BACKGROUND DATA: No one has reported results of pedicle subtraction osteotomies with a 5- to 8-year follow-up. METHOD: Thirty-five consecutive patients with sagittal imbalance (29 females/6 males, average age at surgery, 53.1 years) treated with lumbar pedicle subtraction osteotomies (1 at L1, 13 at L2, 20 at L3, and 1 at L4) at 1 institution were analyzed (average follow-up, 5.8 years; range, 5-7.6 years). Radiographic and clinical outcomes analysis was performed. RESULTS: There were no significant regional radiographic changes between 2 years postoperative and the ultimate follow-up (proximal junctional change, P = 0.30; thoracic kyphosis, P = 0.38; and lumbar lordosis, P = 0.84), although many patients did demonstrate an increasingly anterior C7 sagittal plumb with time. Ten pseudarthroses (29%) occurred in 8 patients and were revised between 2 and 5 years postoperative. There were no pseudarthroses at the osteotomy level (9 at the thoracolumbar junction, 1 at the LS junction), but at the levels added to the previous fusions. There was no degradation in Oswestry and Scoliosis Research Society (SRS) outcome scores between 2 years postoperative and ultimate follow-up (P = 0.23 and 0.90, respectively). Patients reported very good satisfaction (87%), good self-image (76%), good function (69%), and fair pain subscales (66%) at ultimate follow-up. Sagittal vertical axis <8 cm at ultimate follow-up was significant for better SRS outcomes scores (P = 0.038). Eight patients with revised pseudarthroses did not demonstrate poorer SRS outcomes scores (P = 0.52). Those 8 patients were queried after their pseudarthrosis revision surgery. CONCLUSION: Pedicle subtraction osteotomy can provide satisfactory clinical and radiographic outcomes for patients with a minimum 5-year follow-up despite needing pseudarthrosis revision and some component of increasingly positive sagittal vertical axis between 2 years and 5 to 8 years of follow-up. The level of patient satisfaction and self-image subscales were high after more than 5 years of follow-up. Restoration and maintenance of sagittal vertical axis <8 cm were important to the ultimate sagittal reconstruction. PMID- 17873811 TI - A prospective study of brace treatment versus observation alone in adolescent idiopathic scoliosis: a follow-up mean of 16 years after maturity. AB - STUDY DESIGN: The Swedish patients included in the previous SRS brace study were invited to take part in a long-term follow-up. OBJECTIVE: To investigate the rate of scoliosis surgery and progression of curves from baseline as well as after maturity. SUMMARY OF BACKGROUND DATA: Brace treatment was shown to be superior to electrical muscle stimulation, as well as observation alone, in the original SRS brace study. Few other studies have shown that brace treatment is effective in the treatment of scoliosis. METHODS: Of 106 patients, 41 in Malmo (all Boston brace treatment) and 65 in Goteborg (observation alone as the intention to treat), 87% attended the follow-up, including radiography and chart review. All radiographs were (re)measured for curve size (Cobb method) by an unbiased examiner. Searching in the mandatory national database for performed surgery identified patients who had undergone surgery after maturity. RESULTS: The mean follow-up time was 16 years and the mean age at follow-up was 32 years The 2 treatment groups had equal curve size at inclusion. The curve size of patients who were treated with a brace from the start was reduced by 6 degrees during treatment, but the curve size returned to the same level during the follow-up period. No patients who were primarily braced went on to undergo surgery. In patients with observation alone as the intention to treat, 20% were braced during adolescence due to progression and another 10% underwent surgery. Seventy percent were only observed and increased by 6 degrees from inclusion until now. No patients underwent surgery after maturity. Progression was related to premenarchal status. CONCLUSION: The curves of patients with adolescent idiopathic scoliosis with a moderate or smaller size at maturity did not deteriorate beyond their original curve size at the 16-year follow-up. No patients treated primarily with a brace went on to undergo surgery, whereas 6 patients (10%) in the observation group required surgery during adolescence compared with none after maturity. Curve progression was related to immaturity. PMID- 17873812 TI - Classification of high-grade spondylolistheses based on pelvic version and spine balance: possible rationale for reduction. AB - STUDY DESIGN: Retrospective review of a radiographic database of high-grade spondylolisthesis patients in comparison with asymptomatic controls. OBJECTIVE: To analyze the sagittal spinopelvic alignment in high-grade spondylolisthesis patients and identify subgroups that may require reduction to restore sagittal balance. SUMMARY OF BACKGROUND DATA: High-grade spondylolisthesis is associated with an abnormally high pelvic incidence (PI); however, the spatial orientation of the pelvis, determined by sacral slope (SS) and pelvic tilt (PT), is not known. We hypothesized that sagittal spinal alignment would vary with the pelvic orientation. METHODS: Digitized sagittal radiographs of 133 high-grade spondylolisthesis patients (mean age, 17 years) were measured to determined sagittal alignment. K-means cluster analysis identified 2 groups based on the PT and SS, which were compared by paired t test. Comparisons were made to asymptomatic controls matched for PI. RESULTS: High-grade spondylolisthesis patients had a mean PI of 78.9 degrees +/- 12.1 degrees . Cluster analysis identified a retroverted, unbalanced pelvis group with high PT (36.5 degrees +/- 8.0 degrees )/low SS (40.3 degrees +/- 9.0 degrees ) and a balanced pelvic group with low PT (mean 21.3 degrees +/- 8.2 degrees )/high SS (59.9 degrees +/- 11.2 degrees ). The retroverted pelvis group had significantly greater L5 incidence and lumbosacral angle with less thoracic kyphosis than the balanced pelvic group. A total of 83% of controls had a "balanced pelvis" based on the categorization by SS and PT. CONCLUSION: Analysis of sagittal alignment of high-grade spondylolisthesis patients revealed distinct groups termed "balanced" and "unbalanced" pelvis. The PT and SS were similar in controls and balanced pelvis patients. Unbalanced pelvis patients had a sagittal spinal alignment that differed from the balanced pelvis and control groups. Treatment strategies for high-grade spondylolisthesis should reflect the different mechanical strain on the spinopelvic junction in each group; reduction techniques might be considered in patients with an unbalanced pelvis high-grade spondylolisthesis. PMID- 17873813 TI - Diabetes and early postoperative outcomes following lumbar fusion. AB - STUDY DESIGN: Retrospective cohort study using data from the Nationwide Inpatient Sample administrative data from 1988 through 2003. OBJECTIVE: To examine perioperative morbidity and mortality for patients with and without diabetes mellitus following lumbar spinal fusion. SUMMARY OF BACKGROUND DATA: Diabetes has been associated with worse outcomes in a variety of orthopedic procedures including spinal surgery. There is limited evidence that diabetic patients have more complications following lumbar fusion with little published data to support this conclusion. METHODS: Data from 197,461 patients who underwent lumbar fusion were included. Over 11,000 patients (5.6%) with a postoperative diagnosis of diabetes mellitus were identified. Selected variables were used for comparison of patients with and without diabetes. Bivariate statistical analyses compared postoperative complication rates while multivariate statistics were used to determine likelihood of complications with diabetes. RESULTS: Bivariate analysis demonstrated that diabetes was significantly associated with postoperative infection, need for transfusion, pneumonia, in-hospital mortality, and nonroutine discharge (P or=45 degrees were compared with 50 normal patients with thoracic kyphosis <45 degrees . Correlation analysis was performed to identify significant relationships between the magnitude of the major kyphotic curve and the 4 SRS outcome questionnaire domains (Total Pain, General Self-Image, General Function, and Activity). Lower SRS scores indicate an increase in symptoms. RESULTS: The average age of the subjects was 14 +/- 4 years (range, 8-18 years). The thoracic kyphosis varied between 11 degrees and 95 degrees for all subjects. Significant negative correlations were found between kyphosis magnitude and the total pain, general self-image, general function, overall level of activity, and total SRS scores (P < 0.0001). Of the 4 domains, self-image had the highest correlation with kyphosis magnitude while activity had the lowest. CONCLUSION: These findings indicate that higher kyphosis magnitudes were associated with increased pain, lower self-image, and decreased function and activity. Patients with thoracic hyperkyphosis were significantly more symptomatic than normal subjects in all domains. The r values for this analysis of kyphosis (0.40-0.66), in fact were substantially greater than those previously reported for scoliosis magnitude versus SRS Questionnaire scores (0.16 0.26), suggesting this instrument may be even better suited for the evaluation of hyperkyphosis patients. PMID- 17873816 TI - Complications in posterior fusion and instrumentation for degenerative lumbar scoliosis. AB - STUDY DESIGN: Radiographic analysis was performed retrospectively. Outcomes and complications were collected prospectively. OBJECTIVES: To assess complications after posterior fusion and instrumentation for degenerative lumbar scoliosis, to determine risk factors of complications, and to analyze the clinical outcomes of surgery. SUMMARY OF BACKGROUND DATA: The complications after degenerative lumbar scoliosis surgery have reported to be high. Risk factors for developing complications are unknown. METHODS: Forty-seven patients (average age, 66.6 years; range, 48-83 years) with degenerative lumbar scoliosis undergoing posterior fusion and instrumentation were analyzed. Seven patients had additional posterior lumbar interbody fusion at the lumbosacral junction. The average number of levels fused was 4.7 +/- 2.2 segments. We evaluated the early perioperative (<3 months after surgery) and late complications. RESULTS: There were 14 early perioperative complications and 18 late complications. There was 1 case of mortality by pulmonary embolism. Early complications included ileus, urinary tract infection, transient delirium, superficial infection, and neurologic deficit. Late complications included adjacent segment diseases, pseudarthrosis, and loosening of screws. Adjacent segment disease developed at the proximal segment in 10 patients and at the distal segment in 5 patients. Pseudarthrosis was noted at the lumbosacral junction in 2 patients. Revision surgery was performed in 7 patients. Older patients (>65 years) had the tendency to increase early complications without statistical difference (P = 0.053). Excessive intraoperative blood loss was the most significant risk factor for the development of early perioperative complications, and number of levels fused was related to blood loss. Operative time and multiple medical comorbidities were not associated with higher complication rate. There were no specific factors related to the development of late complications. CONCLUSION: The complication rate after posterior fusion and instrumentation for degenerative lumbar scoliosis was 68%. Abundant blood loss was a significant risk factor for early perioperative complications. The improvement of Oswestry disability index was less in patients with late complications. PMID- 17873817 TI - Adult spinal deformity surgery: complications and outcomes in patients over age 60. AB - STUDY DESIGN: A retrospective analysis, including prospectively collected patient outcomes data. OBJECTIVE: To determine the rate of complications and outcomes in patients >or=60 years of age who underwent major spinal deformity surgery requiring a minimum 5-level arthrodesis procedure. SUMMARY OF BACKGROUND DATA: As the population ages, an increasing number of older patients are presenting with spinal deformity disorders that may require major reconstructive procedures. Previous studies have reported complication rates as high as 80% in this age group for 1- and 2-level fusion procedures. The prevalence of complications was found to increase with the greater number of levels fused. METHODS: Forty-six patients who were 60 years of age or older underwent a thoracic or lumbar arthrodesis procedure consisting of 5 levels or greater. Diagnosis, comorbidities, operative data, hospital data, major and minor complications, and deaths were recorded. Oswestry Disability Index (ODI) Scores were used to evaluate clinical outcomes. RESULTS: Thirty-eight females and 8 males with a mean age of 67 years (range, 60-85 years) and a mean follow-up of 4.2 years (range, 2 11 years) had complete records. Thirty-six (78%) patients had at least 1 comorbidity. Twenty-nine (63%) patients had at least 1 prior spinal surgery. A mean of 9 levels (range, 5-16 levels) were fused in each patient. The overall complication rate was 37%. The major complication rate was 20%. ODI improved from 49 to 25 for a mean improvement of 24 (49%) (P < 0.0001). CONCLUSION: The overall complication rate was 37% and the major complication rate was 20%. Increasing age was a significant factor (P < 0.05) in predicting the presence of a complication. Patients older than 69 years had more complications. The presence of a comorbidity had no association with complication rates and neither had an effect on final patient reported outcomes, which showed significant improvement (ODI preoperative, 49; postoperative, 25) (P < 0.0001). PMID- 17873818 TI - Neurologic complications of lumbar pedicle subtraction osteotomy: a 10-year assessment. AB - STUDY DESIGN: Clinical, radiographic, and outcomes assessment focusing on neurologic complications in patients undergoing pedicle subtraction osteotomy (PSO). Clinical data were collected prospectively. Radiographic analysis was performed retrospectively. OBJECTIVE: To evaluate intraoperative and postoperative neurologic deficits following lumbar PSOs in order to determine risk factors, treatment strategies, and patient outcome. SUMMARY OF BACKGROUND DATA: Although technically demanding, PSOs have been increasingly used to restore lumbar lordosis and correct sagittal deformity. Although some reports have commented on various complications of the procedure, to our knowledge, there have been no studies focusing on neurologic complications of the osteotomy. METHODS: An analysis of 108 consecutive patients with an average age of 54.8 +/- 14.0 years and treated with a lumbar PSO at 1 institution over a 10-year period (1995 2005) was performed. Medical records, radiographs, and neuromonitoring data were analyzed. Clinical outcome was assessed using the Oswestry Disability Index and the Scoliosis Research Society (SRS)-24 instruments. RESULTS: A total of 108 PSOs were performed. Following surgery, lumbar lordosis increased from -17.1 degrees +/- 19.3 degrees to -49.3 degrees +/- 14.7 degrees (P < 0.000), and sagittal balance improved from 131 +/- 73 mm to 23 +/- 48 mm (P < 0.000). Intraoperative and postoperative deficits (defined as motor loss of 2 grades or more or loss of bowel/bladder control) were seen in 12 patients (11.1%) and were permanent in 3 patients (2.8%). With time motor function improved by 1 grade in 2 patients and all 3 were able to ambulate. Intraoperative neuromonitoring did not detect the deficits. In 9 patients, additional surgical intervention consisted of central enlargement and further decompression. Deficits were thought to be due to a combination of subluxation, residual dorsal impingement, and dural buckling. CONCLUSION: Intraoperative or postoperative neurologic deficits are relatively common following a PSO; however, in a majority of cases, deficits are not likely to be permanent. PMID- 17873820 TI - Surgical revision rates of hooks versus hybrid versus screws versus combined anteroposterior spinal fusion for adolescent idiopathic scoliosis. AB - STUDY DESIGN: Multi-institution retrospective review. OBJECTIVE: To determine the surgical revision rates of hook, hybrid, anteroposterior, and total pedicle screw constructs for adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Much debate continues on the safety, efficacy, and cost of thoracic pedicle screws. Nonetheless, there are no large series that have evaluated the revision rate of various constructs in AIS to determine the need for repeat surgery, and therefore, the added indirect costs and risks of additional procedures. METHODS: We retrospectively reviewed the surgical case logs of 1428 patients with AIS at 2 institutions from 1990 to 2004, and the clinical records and radiographs of revision cases. Patients were classified into 1 of 4 groups: hook, hybrid hook and screw, all pedicle screw, and combined anteroposterior fusion constructs. Overall, there were 65 (4.6%) returns to the operating room, or 55 (3.9%) cases after excluding infections without concomitant pseudarthrosis. RESULTS: Of the 65 revision cases, there were 52 females and 13 males, at an average age at first surgery of 13.9 years (range, 9-18 years), and an average age at revision of 14.7 years (range, 12-23 years). For the revision cases, the average initial Cobb was 61.9 degrees (range 44 degrees -110 degrees ), and this was not statistically different within the cohorts (P > 0.05). In terms of revision rate, all hook constructs had a higher revision rate secondary to instrumentation failure when compared with screws, while both hook and hybrid constructs had an overall higher surgical revision rate when compared with screw constructs or anteroposterior constructs (all P